- Email: [email protected]
Role of electrophysiologic testing in the diagnosis and treatment of patients with known and suspected bradycardias and tachycardias
Role of Electrophysiologic Treatment of Patients Bradycardias
Testing in the Diagnosis and With Known and Suspected and Tachycardias John D. Fisher
E
testing has LECTROPHYSIOLOGIC made possiblemore accurate diagnosisand treatment of recurrent tachycardias and syncopal episodes. The rapid expansion in clinical electrophysiology is reflected both in the number of reports in the literature and in the texts, monographs, and reviews appearing in recent years. ‘-* The challenge for the 1980swill be the continued refinement of present studies and the identification of high-risk patients for the development of bradycardias or tachycardias who warrant prophylactic treatment. Over the last decade, a battery of tests has been developed to assessthe electrophysiologic function of cardiac tissues.The details of these tests vary among investigators. Occasionally, differences in investigators’ assumptions,experience, or definitions may result in marked differences in viewpoints or conclusions, much to the consternation of the unwary reader. This article will review some of the electrophysiologic tests and procedures currently in use, their applications, and reliability.
Signal
When a wave front passesdirectly underneath the recording electrode it produces an “intrinsic deflection” on the electrogram that has highfrequency components. Depolarizations distant to the electrode give rise to lower frequency potentials at the recording site of a magnitude proportional to the tissue massundergoing excitation. When 40-500 Hz filters are used to measure far-field events, including ventricular depolarization during a His bundle study, the low-frequency potentials are lost, possibly giving an erroneoustiming for distant events. Catheterization
The surface electrocardiogram reflects *predominantly the sum of low-frequency highamplitude signals that reach the body surface from the working myocardium. The specialized conduction system generates low-amplitude potentials that do not reach the body surface well. Although some success has been reported in recording His bundle electrograms from the body surface using signal averaging techniques,9-‘2the technique is limited because the His bundle potential is submerged in the left atria1 depolarization unlessthere is a long P-R interval. Additionally, pacing maneuvers that add much to the scope of clinical electrophysiologic tests cannot be performed with surface His bundle studies. In contrast, temporary transvenous pacing leads can be positioned strategically for both pacing and recording localized endocardial signals.
in Cardiovascular
Diseases,
Vol.
24, No.
1 (July/August),
Techniques
Most commonly, transvenous pacing catheters are inserted percutaneously using the femoral veins, and are advanced to the heart under fluoroscopic control.‘s-‘7 The His bundle electrogram is somewhat more difficult to record from the brachial, subclavian, or jugular route, but may be accomplished with patience. Complex maneuvers and tip-deflecting catheters have been described for performing His bundle electrograms from the superior approachnm2’but are not really necessary.2’-22His bundle electrograms may be recorded during the withdrawal of a standard temporary pacemaker lead previously inserted by the subclavian route. Indeed, His bundle electrograms can be performed at the bedside without fluoroscopic assistance during the insertion of a temporary transvenous pacemaker by the superior approach.2’ Balloontipped leads, analogousto Swan-Ganz catheters, also have been used.23
THEORY AND TECHNIQUES
Progress
Filtering13v14
From the Department of Medicine, Division of Cardiology, Montejiore Hospital and Medical Center, and the Albert Einstein College of Medicine. Bronx, N. Y. Reprint requests should be addressed to John D. Fisher. M.D., Cardiac Catheterization Ofices. Montefiore Hospital and Medical Center. 111 East 210th Street, Bronx, N.Y. 10467. o 1981 by Grune & Stratton, Inc. 0033-0620/81/2401-0002$05.00/O
1981
25
26
Choice of Intracardiac
JOHN
Signals (Fig. I)
His bundle studies usually are recorded with a tripolar catheter draped across the tricuspid valve for recording the filtered localized signals of the low medial right atrium His bundle and right ventricular inflow. Another lead is positioned in the high right atrium at the junction of the superior vena cava for pacing and recording near the sinus node. For more complex studies, such as those involving tachycardias, additional leads (often of a multipolar design) are inserted. The coronary sinus lying in the atrioventricular groove presents a convenient transvenous approach to recordings of the left atrium and left ventricle. Influences on the Timing of Cardiac Intervals
Changes in sympathetic and parasympathetic tone can profoundly influence the heart rate and timing of the cardiac intervals.24’25 Such changes in neurohumoral tone can be brought about by anxiety, exercise, and other voluntary and involuntary factors. Fortunately, changes in autonomic tone do not appear to exert significant influences during electrophysiologic testing.26 Impulse formation and conduction also can be affected by factors such as ischemia and pharNORMAL
RANGES
(‘2 SD)
initial deflections
Fig. 1. Normal values and catheter positions for electrophysiologic studies. In this example, three ECG leads are displayed along with four intracardiac leads filtered at 4G-500 Hz: high right atrium (HRA). His bundle electrogram [HBE), low lateral right atrium (LLRAI, and coronary sinus (CS). Intervals are in milliseconds. Other abbreviations: SAN, sinoatrial node; RA, right atrium; LA, left atrium; TV, tricuspid valve; HB. His bundle: RV, right ventricle: LV, left ventricle. The P-A, A-H, and H-V intervals are explained in the text.
D. FISHER
macologic agents. Each of these factors must be taken into account when interpreting results of an electrophysiologic study. Baseline
Intervalsz7
The P-R interval may be divided into four parts. The P-A interval reflects conduction between the sinus node and the AV node and ranges (f 2 SD) between 9 and 45 msec.25 The A-H interval reflects conduction through the AV node and normally varies between 54 and 130 msec. The H-V interval (3&55 msec) is a measure of conduction in the His bundle and bundle branches (the His-Purkinje system), while the H potential gives information about the His bundle itself. Validation of the His Bundle Potential28*29
Deflections following the A wave may represent the atria1 “T” repolarization wave, part of the atrium, the His bundle potential, or a right bundle branch potential. When the apparent His bundle potential has been maximized for size and consistency, His bundle pacing should be attempted. Capture of the His bundle is recognized when the pacer impulse (PI) to QRS remains the same as the onset of the His bundle potential to QRS prior to pacing, and the QRST configuration is the same as during normal sinus rhythm during His bundle pacing. There are, however, two exceptions to these rules. (1) His bundle pacing may result in atria1 capture or in retrograde conduction to the atrium, and the retrograde P wave may distort the QRS complex. (2) Patients with bundle branch blocks during normal sinus rhythm may exhibit normalization of the QRS complex during His bundle pacing. This is ascribed to longitudinal dissociation within the His bundle, with the bundle branch block caused by disease in committed fibers proximal to the location of His bundle pacing.30p31 Establishing Onset of Ventricular Depolarization
The significance of a prolonged H-V interval has been the subject of much dispute,32-35 partly because investigators differ in the definition of the H-V interval itself. The H-V is measured
ELECTROPHYSIOLOGIC
27
TESTING
variously from the onset of the His bundle depolarization to the onset of the QRS in the peripheral ECG (sometimes called the H-Q interva1);33,36to the onset of the V in the intracardiac lead;” or to the onset of the ventricular depolarization wherever it is observed first.34.38 Since the purpose of measuring this interval is to establish the conduction time through the His-Purkinje system, it seems most reasonable to measure the onset of the ventricular depolarization in whichever lead it is observed first. Three mutually perpendicular peripheral ECG leads (leads, X, Y, and Z or leads 1, AVF, and VI) may not suffice to reflect accurately the onset of ventricular depolarization: in 23% of a series of 100 patients, recordings of the His bundle electrogram at 0.1-2000 and of the right ventricular apex at 0.1-2000 and 40-500 Hz resulted in an H-V interval at least 10 msec shorter than the conventional H-V interval recorded at 40-500 Hz alone.13 Electrophysiologic
Stresses
depressant effects on both sinus and AV nodes, carotid massage in patients with AV nodal Wenckebach generally results in worsening of the block. If the Wenckebach is at the HisPurkinje level, the slower sinus rate gives the His-Purkinje system more time to recover, and thus the degree of block may be improved. CSM should generally be avoided in patients with carotid bruits or histories of cerebral vascular accidents. Ventricular arrhythmias have occasionally been reported with CSM,S4,55typically associated with digitalis therapy. A reversal or mirror image of this test can be accomplished by using atropine. Diseaseof both sinoatrial and AV nodes in the same patient is common.57In a patient with sick sinussyndrome who responsds to carotid massage with sinus arrest, atria1 pacing during CSM will reveal whether AV nodal hypersensitivity also exists, This information can help determine whether an atria1 or ventricular pacer is appropriate for that patient.
and Maneuvers
In addition to data collected during passive recordings in normal sinus rhythm, stressescan be applied to specific parts of the conduction system. Carotid Sinus Massage (CSIV)~,~~-~~ CSM results in three types of cardiovascular effects: (1) cardioinhibitory (sinus arrest, AV block), (2) vasodepressor(hypotension), and (3) cerebral, i.e., syncope without bradycardia or hypotension, possibly due to cerebral ischemia and typically seenonly with prolonged CSM.39,40 The relative incidence of these signs in normal subjectscompared to those with syncope or overt cardiovascular disease has been the object of considerable investigation and controversy.8,39d8 CSM exerts its cardioinhibitory effects primarily on the sinus node (especially right CSM) and AV node (left CSM), resulting in slowing of the sinus rate and prolongation of the P-R interval or AV block due to lengthening of the A-H interval.39ds Block in the His-Purkinje system due to carotid sinus massageis distinctly rare, although it has been reported.56 In patients with Wenckebach phenomenon, CSM is often useful as a bedside test to determine the location of the block. Because of its
Exercise Exercise results in a number of neurohumoral changes, including a decrease in parasympathetic and an increase in sympathetic tone. Heart block at the level of the AV node may be improved by exercise and that due to HisPurkinje system diseaseworsened.59 Breath Holding In five normal subjects,60breath holding for as long as possible during maximum inspiration and during maximal expiration resulted in insignificant changes in the cardiac rhythm and rate. Some patients, however, exhibit profound changes.The most extreme examples are seen in patients suffering from the sleep apnea syndromes, who may have prolonged sinusarrest or heart block and during pacing develop Wenckebach at very low rates6’y6* Psychologic Stresses Many episodesof syncope or suddendeath are preceded by a period of psychologic stress.63 During electrophysiologic testing, psychologic stressescan influence the basic intervals, usually resulting in an increased sinus rate and shortening of the A-H interval.64
28
Incremental
JOHN
Pacing
The pacing rate is increased, usually in 10 beat per minute (bpm) steps, for a time sufficient to allow a steady-state response or “accommodation”65 to develop. This time may be as little as a few seconds or as long as 45 sec. Burst Pacing While the patient is in spontaneous rhythm the pacemaker is turned on suddenly, usually for a short burst of 10 or 20 stimuli. Bursts, designed to produce 1: 1 capture, may be at any rate, but the effects are most noticeable at short cycle lengths. Bursts are most commonly used for the induction and termination of tachycardias. Trains Short series of rapid stimuli designed to effect a single capture. Ramp Pacing Cardiac refractory periods are dependent on the preceding cycle lengths, and a sudden rapid burst may result in 2:l capture because of the long refractory period generated by the slow spontaneous rhythm. With incremental ramp pacing, higher rates with 1:l capture can be achieved because pacing is begun at a low rate and gradually increased over a period of seconds until a target rate is achieved or 1:l capture finally is lost. Because the refractory period is set by the preceding cycle length, which is being shortened continuously, the refractory period also shortens, allowing a higher maximum rate with 1:l capture than is possible with burst pacing. Rapidly incremental ramps are useful for induction and termination of tachycardias. Very slow ramps may be useful for assessing refractory periods of normal and abnormal pathways (see below). Decremental ramps, with gradual reduction in pacing rate, may help in the termination of some tachycardias. Programmed Programmed
Extrastimuli (PES) and Electrical Stimulation (PES)
The Extrastimulus Technique During the baseline rhythm, which may be spontaneousor paced, extrastimuli are adminis-
D. FISHER
tered by a special pacemaker that can be programmed to deliver the extrastimuli at any desired point during the cardiac cycle. In practice, the PES usually begins late in diastole and is repeated with increasing prematurity until the refractory period is reached. The stimulus conventionally is limited to between two and four times the threshold for capture. At lower outputs, erroneous interpretations are possibleif the threshold changes slightly. At higher outputs, there may be increased risk of “nonclinical” fibrillation, although a more accurate estimation of the absolute refractory period is possible. Eight or more beats occur between each PES to allow full return to the basic rhythm. Multiple as well as single PES may be used. PES are used in sinus node function tests, in the determination of cardiac refractory periods, and in the initiation and termination of tachycardias. Each of these roles will be described in detail below. Pharmacologic Stresses (Table 1)8*66-73 Pharmacologic agents affect different portions of the cardiac impulse formation and conduction systems allowing specific stressesor manipulations. Drugs chosenfor use will depend on the problem of the patient undergoing study. The effects of commonly used drugs, outlined in Table 1, suggest the difficulty in making a rational choice of agents. Additional new drugs are undergoing clinical trials and may have their own unique properties.69*72-76 Agents widely used for other purposesmay have potent electrophysiologic effects.79-8’ Attempts to classify drugs according to their cardiac electrophysiologic effects have enjoyed some success,69*70,82-84 but frequent exceptions have made these schemes rather cumbersome. The pharmacokinetics and duration of action of each agent must be considered, especially if the effects of several agents are to be tested.“-” Drugs such as lidocaine and edrophonium have relatively short half-lives. After a single bolus of 100 mg, lidocaine blood levels become subtherapeutic in as little as 6 min.‘* When rapidly infused, procainamide’s electrophysiologic effects may be undetectable after 1 hr.89Most other agents are longer lasting, and if separate studieson several are required, it may be necessary to extend the testing period over several days.
ELECTROPHYSIOLOGIC
TESTING
29
30
JOHN
THE “COMPLETE”
Sinoatrial
Node
(Table 2). Abnormal heart rates due to excessive autonomic tone may occur even if the sinus node itself is normal, i.e., a “pseudo-SSS” exists.
ELECTROPHYSIOLOGIC STUDY
(SAN)
Function
Tests
Carotid Sinus Massage
Pathophysiology of the Sick Sinus Syndrome (SSS)
Prolonged sinus arrest or AV block with carotid sinus massageor pressure in a patient with recurrent syncope are probably grounds for implantation of a permanent pacemaker.5~52
The SSS9W92is a collection of conditions, rather than a single entity, and is characterized by a sinus mechanism with an atria1 rate that is inappropriate for physiologic requirements. Unphysiologic bradycardia and tachycardia may coexist in the sameindividual as the brady-tachy syndrome (BTS). The tachycardia part of the BTS may be due to atria1 fibrillation or AV nodal reentrant supraventricular tachycardia, which is not surprising in view of the frequency of multilevel disease.s7 Inappropriate sinus tachycardia may be due to increased automaticity or to reentry and will be discussedin a later section. Sinus bradycardia may be caused by several mechanisms, each of which must be sought during a complete electrophysiologic study:93*94(1) intrinsic depression of automaticity, (2) conduction block in the sinus node and perisinus nodal tissues, and (3) hypersensitivity to autonomic influences, especially vagal tone. A battery of tests have been developed to help distinguish among the different forms of SSS
Table
Intrinsically
SA node
poor
2.
Sinus
Node
Function
automaticity
Wagal
tone
sensitivity
prolongs
Sinus Node Recovery Times (SRT, SNRT) One of the characteristics of automatic foci such as the sinus node is “overdrive suppression”: pacing at rates in excess of the spontaneous rate of the automatic focus results in a temporary inhibition of spontaneousdepolarization of the automatic focus, with gradual return to the original cycle length over several beats after cessation of pacing. In normal patients, pacing the atrium at approximately 120 bpm for a minimum of 15 set results in reproducible sinus node recovery times defined as the interval from the last pacing impulse until the first sinus node recovery beat.” by the third recovery beat, the sinus rhythm has returned to the basic cycle length f 250 msec (Fig. 2, normal response). The normal range of SNRTs (Table 3) varies widely among investigators,27~9”‘osmaximum durations approximating 1500 msec being typi-
Tests
in Apparent
Sick
Sinus
Expected Vagal
Sinus Node
Tone
Test
Decreased
CSM SNRT
to normal
sinoatrial
tone
conduction
times.
Rapid
Increased
CSM SNRT SACT
Decreased
CSM SNRT SACT
pacing
used
Syndrome
Result Further
durig
the
SNRT
test
slowing
Prolonged Normal Further slowing*
SACT CSM SNRT SACT
Decreased
block
Vagal hypersensitivity Excess vagal tone
Excess
D. FISHER
Variable Prolonged Little change Variable* Prolonged* Further slowing Normal+ Normal may
fail
to penetrate
hypervagotonia exists, thus failing to cause overdrive suppression. However, exit of sinus beats may also be impeded. TTachycardia (pacing) induced vagal tone may result in prolongation. Secondary pauses may occur if vagal tone increases hypertension related to initial recovery beats. CSM: carotid sinus massage; SACT: sinoatrial conduction time; SNRT: sinus node recovery time.
the
sinus
node
in response
if to
ELECTROPHYSIOLOGIC
31
TESTING
Fig. 2. Sinus node recovery time schematic. The heart rate and cycle length are represented on the ordinate. The first part of the abscissa is compressed and represents several minutes of baseline sinus rhythm and atrial pacing. Subsequently, the abscissa is calibrated in numbers of recovery beats following cessation of atrial pacing. The heavy line represents the normal response: from a baseline sinus rate (NM) of approximately 70 bpm the patient is paced at a rate of approximately 125 bpm. Upon cessation of pacing the first recovery beat normally occurs in less than 1500 msec and the rate returns to baseline after a few beats. The lighter lines show typical abnormal responses (see text).
Atrial ‘i
I\Pacing
\
off t
I JSR
cal. Corrections for differences in the baseline sinus cycle length commonly are applied. The corrected sinus node recovery time (SNRTC or CSNRT) usually is calculated in one of four ways. (1) The basic sinus rhythm cycle Iength in msec is subtracted from the sinus node recovery time to give the CSNRT with normal ranges varying between 350 and 550 msec. (2) The corrected sinus node recovery time is expressed as a percentage of the baseline cycle length, normal values ranging up to 180%. The uncorrected sinus node recovery time appears to differentiate between normal and sick sinus node patients at least as well as these corrections (Table 3). (3) Regression equations have been proposed9’.‘06 with an upper limit of normal SNRT of 1.3 (means sinus cycle length in msec) + 101 msec. (4) Clinical dennervation of the sinus node94 using 0.2 mg/kg of propranolol followed by 0.04 mg/kg of atropine results in an “intrinsic sinus rate.” This method may help to distinguish patients with true sick sinus syndrome from those whose normal sinus nodes are under the influence of excessive vagal tone.
I
I
1
2345678910
I
I
RECOVERY
I
I
I
I
I
1
BEAT
Pacing at 120-l 30 bpm for 15 set produces reproducible results in normal subjects, i.e., a scatter of less than about 250 msec on successive trials, with little differences if pacing is carried out for a longer period of time.95-97*lo7 Normals may show a modest decrease in the SNRT after faster pacing95~97*‘0’due to autonomic adjustment to pacing-related anxiety or hypotension. Abnormalities seen in patients with SSS are outlined in Fig. 2, and include the following: (1) markedly prolonged SNRT; (2) a wide scattering of the SNRT when many trials are carried out;“’ this or short SNRTs may indicate failure of some pacing stimuli to enter the SAN, i.e., some degree of SAN block. (3) prolongation of the SNRT after pacing at more rapid rates or for longer periods in patients where normal values were observed with slower pacing rates or durations? (4) the normal response after an SNRT is a gradual return to the baseline cycle length that usually occurs within 3-4 beats. A “secondary pause” exists if the beats following the sinus node recovery time do not return to normal and the sinus rate remains depressed, or if there is a return to normal with a subsequent persistant or transient decrease in rate.“’ (5) Ectopic beats or rhythms.
15
93,105
ID4
299
57
11
-
20
ID3
1,044
30
1,062
921
1,lDo
-
102
-
too 101
1,026
20
958
-
99
452
98 32
34
27
97
-
1,041 -
43 27
95
996
SNRT
Subjects
Ref
MM”
Number
207
172
-
12571
1,499t
1,476
1.265
1,476
1,460
216
190
1,342
1,256
-
1,680
1.775 -
+zstl
-
lmsecl
-
158
149
-
346
367 -
*SD
SNRT
Normals
w
Table
29%
16.5%
129%
131 -
113
119
-
23%
155
107
-
279
96
6.6%
*SD
SNRTc*
Sinus
133
-
3.
232
210
270
295
-
134%
252
180
119% -
171
260
SNRTc
Mea”
Controls
1245)
519t
-
496
-
472
496
533
-
562
394
-
456 729
-
+ZSD
“Isac
Node
BY
I1911
l6l+
162
-
_-
--
-
-
180
-
-
177 .-
159 -
137
-I- 2SD
PWCB”t
Recovery
3
N
-e
13
14
17
41
19
19 -
14
19
26 -
Times
-
1.361
1,006
-
2.110
1,401
2.064
2.209
-
-
4,732 -
SNRT
Mea”
(SNRT)
306 -
249
-
1,269
393
1,326
1,096
-
-
719 -
*SD
SNRT
1.977 -
1,504
-
4,646
2.187
4.720
4.402
-
-
6.170 -
+2SD
o(
Max
130%
276
680 -
1,016
-
961 -
1,133
147%
31%
293
-
1,335
-
864
-
3.350
3,362
-
1.183
3,467 -
3,376
1,253 -
1,122
3.110
1,092 -
-
ZSD
1.009
23
SNRTc
-
Syndrome
+SD
Sinus
SNRTc
MW”
Sock
BY
192
-
-
-
-
-
193 -
-
-
-
+ZSD
Percent
61
I
I
I
73 53
37 94
SNRTc bv %
SNRTc SNRT 22
SNRTc SNRT
SNRTc SNRT
SNRTc SNRT
26 35
14
35
-
I 10379
-
-
100
Percent A”W”Wl*
ELECTROPHYSIOLOGIC
TESTING
SAN
NSR
ATRIUM ZONE
1
Non-Reset AIA~= ~AIAI AZAJ Prolongs Fig. 3. Sinoatrial conduction time schematic of premature beat method (Strauss at al. sea text). The sinoatrial node (SAN) depolarizes unseen and results ultimately in atrial depolarization, designated here as Al. In performing this test, premature atrial beats (A21 ara introduced with increasing prematurity and the timing of the return cycle lA3) is analyzed. The sinoatrial conduction time is calculated from zone II responses.
ZONE
2*
Reset AIAW ~AIAI AzAs Constant
ZONE
3
SAN Entry Block AIAJ~AIAI (AZ lnterpobted ) ZONE 4 ?SAN Reentry AI A3 < At AI (SAN Gap)
*SACT=A~J-A%I
The Sinoatrial Conduction Time (SACT, Sinoatrial Block Test) Direct recording of low-amplitude sinus node potentials requires microelectrode techniques in vitro’09.“0 or special equipment in vivo.“‘,“2 Clinically, two indirect tests of sinoatrial conduction are in use. The first, described by Strauss et al. (Fig. 3)98 involves programmed extrastimuli (PES) given in the region of the sinus node during sinus rhythm (designated Al). Premature beats not resulting in reset of the sinus node are termed zone I. Zone II occurs when the PES (A2) is given with sufficient prematurity so that it can enter into the sinus node and depolarize it prematurely. This results in a pause that is less than compensatory. The return beat, designated A3, is presumed to originate in the sinus node exactly one basic cycle length (Al Al) after the
/
NSR
\
ATRIAL I
SACT=
PACING
AX~-~I
(Divide
by 2 for l-way
SACT)
node has been reset by the A2. Earlier premature beats in zone II may depress sinus automaticity to some degree, resulting in a prolongation of subsequent spontaneous cycles, A3A4,9”,“3 or a shift in sinoatrial pacemaker.‘14 Later premature beats in the one-third of zone II adjacent to zone I may give more meaningful results. This area has been designated zone IIa.98 With increasing prematurity of A2, the onset of zones III and IV is heralded by a cacophony of responses. Narula has described a second method of estimating the SACT not requiring the use of special pacing equipment (Fig. 4).“’ It assumes that pacing the atrium at rates of 10 bpm or less above the sinus rate will not result in significant overdrive suppression of the sinus node, but that the pacing beats will gradually achieve capture and reset of the sinus node. These two methods
RATE SLIGHTLY
ABOVE
(Divide by 2 for l-way
NSR \
RECOVERY
SACT)
Fig. 4. Sinoatrial conduction time schematic. Atrial pacing method {Narula). Once again, the sinoatrial node depolarizes unseen and ultimately results in an atrial depolarization (Al I. Instead of premature beats, atrial pacing at a rate slightly above that of the sinus rate is used as A2. It is assumed that such atrial pacing will ultimately depolarize the sinus node without significant overdrive suppression. The sinoatrial conduction time is then calculated as for the premature beat method (see text).
34
JOHN
result in somewhat similar values for the SACT, but the importance of disparities is not yet resolved.1’6 Sinoatrial conduction times in patients with and without evidence of sinus node disease (Table 4). 93,97-‘oO.‘OZ,‘O4.“7The upper limits of normal (+2SD) in 176 patients (Table 4) is 147 msec using the Strauss technique and “one-way” SACT. The total or 2-way SACT would be 294 msec (+2 SD). Some investigators consider SACTs beyond + 1 SD as abnormal.98 Normal ranges for the Narula method have not yet been established, as previous reports”5s”6 have combined data from patients with and without sinus node disease.
normal response to 1 or 2 mg of intravenous atropine is an increase in the sinus rate to 90 bpm or 20% above the baseline level.90*98Sinus node recovery times performed in the presence of atropine generally are shorter than baseline,lz3 but paradoxical prolongations have been described.‘24 It is possible that in these patients atropine permits 1: 1 entry of the pacing impulses into a diseased sinus node and a greater degree of suppression than was possible without the drug. The combined use of atropine and propranolol has been discussed above.94 LidoCaine, 100-l 50 mg intravenously, and edrophonium, 15 mg intravenously in divided doses of 7.5 mg 1 min apart, do not significantly affect the sinus node recovery time in normal subjects.‘25,‘26 In patients with the sick sinus syndrome, however, marked prolongation may occur in response to these drugs, even when the sinus node recovery time was normal prior to their administration.‘25.‘26
Sinus Node Function in Ischemic Heart Disease Acute myocardial infarction can produce sinus bradycardia and marked prolongation of the SNRT,‘18q”9 although the overall incidence of overt sinus node dysfunction is not high, occurring in 20 of 43 1 patients in one series.“’ In the presence of other indications for temporary pacing, evidence of sinus node abnormalities during acute infarction occurred in 17 of 49 patients.12’ Among patients with chronic coronary artery disease, stenosis proximal to the origin of the sinus node artery is associated with abnormal sinus node function tests, with the SACT more sensitive than the SNRT.“’ Carotid sinus hypersensitivity also is common in the presence of coronary artery disease.12’ Pharmacologic
Clinical Usefulness Function Tests
Pharmacologic agents have been used in the assessment of sinus node function (Table 1). A 4.
Sinoatrial
Conduction
of Sinus Node
Most investigators have concentrated on the ability of sinus node function tests to distinguish between patients with known sinus node disease and a control population. The question of whether therapeutic action should be taken on the basis of normal sinus function tests has been addressed less frequently. In a patient with unexplained syncope, a sinus node recovery time of 5 set probably would lead to the implantation of a pacemaker. Whether a pacemaker should be implanted for values just outside the normal ranges is less clear. In
Stresses
Table
Times
(SACT):
“One-way”* Sect Sinus
Max
A”dlO,S
Reference 88 -
35 -
Syndrome
Number
Mean
Max
+2SD
Of
6ACT
+ 2SD
lmsecl
Subjects
169
or
*SD
(ms-scl
46 -
206 -
20 -
16
86
43
180
27
19 -
113 -
66 -
226 -
47 (1001
hsecl
65
22
128
92
30 -
162 -
62
18
120
18 41
181 12s
18 47
217 219
30
172
14
128
27
182
29
143
24
124
68
240
112 86
cf
113 -
24 -
120 -
-
D. FISHER
41 0 26
ELECTROPHYSIOLOGIC
TESTING
elderly patients with sinus bradycardia and symptoms, a prolonged corrected sinus node recovery time may militate strongly in favor of pacemaker implantation.‘27 The value of sinoatrial conduction tests often is diminished by uninterpretable results (e.g., “scatter” graphs12’), but definitely abnormal sinoatrial conduction times are associated with a very high incidence of overt sinus node disease.“’ Nevertheless, an abnormal sinoatrial conduction time in an asymptomatic patient does not warrant the implantation of a pacemaker.“’ The likelihood of recording diagnostic abnormalities in a patient with previously documented sinus node disease increases with the number of variations of sinus function tests employed. At present, the minimum abnormalities that justify the implantation of a pacemaker remain a matter of individual opinion. The Atrium Conduction
From Sinus Node to Atrium
Earliest activation of the atrium typically occurs in the high right atrium near the junction of the superior veaa cava. Earliest activation may, however, occur elsewhere, often in the midlateral right atrium.‘29 This is consistent with the concept of the sinus node as an elongated structure with multiple pacemaker cells whose dominance may shift with autonomic tone, with multiple points of possible exit into the atrium.‘30*‘3’ Internodal conduction is recorded as the P-A interval or, during pacing, as the PI-A. Three specialized internodal pathways have been proposed: anterior, middle, and posterior, somewhat analogous to the His-Purkinje system in the ventricle.‘32.‘33 This concept is supported by demonstration of sinoventricular conduction’34 and its mirror-image (high atrium depolarized first in some subjects during ventricular pacing and retrograde conduction),‘35 animal studies,‘33 and production of AV dissociation during surgery involving areas traversed by the pathways.131 Pacing at different sites may alter the A-H interval. Left atria1 pacing may cause a shorter A-H interval at a given pacing rate than does high right atrial pacing,‘36,‘37 possibly due to a lower insertion of the posterior internodal tract into the AV node. However, others have found no change or inconsistent changes in the A-H, depending on pacing site.“’
35
There is some dispute about the internodal pathways. In humans, these pathways do not consist of continuously linked specialized conducting cells.‘39 Rather, these cells are common throughout the subendocardial layer of the atrium’40,‘4’ but may occur with increased frequency along the routes of the intranodal pathways, which in turn occur along thicker bands of muscle that might in themselves facilitate more rapid conduction. With incremental atria1 pacing, the P-A interval, redesignated PI (for pacer impulse) to A interval, may remain unchanged, but pro10ngs’42,‘43 in as many as 60% of patients by 15 msec or more.‘42 This prolongation usually occurs at the lowest pacing rates but sometimes is delayed until faster pacing. Whether the PI-A remains constant or prolongs does not appear to be related to specific cardiac diseases or to normalcy, but appears to be a random phenomenon. It may be that where the PI-A prolongs, the impulse has failed to gain access to the specialized conduction system of the intranodal pathways or perhaps that in these patients, such specialized pathways do not exist as functional entities. There may also be a period of “latency” between stimulus and atria1 response, but observations in our laboratory, using closely spaced quadripolar leads, suggests that PI-A prolongation is due to slowed conduction rather than latency. Interatrial conduction’44’46 in dogs proceeds via a superiorly situated Bachman’s bundle and an inferior pathway.‘44S’45 In man, these pathways are as evasive histologically as the internodal tracts. Programmed extrastimulation of the atrium is used to determine sinus node conduction times and atria1 and conduction system refractory periods, discussed in a greater detail later. Refractory periods normally are similar in different parts of the atrium. Marked dissimilarities may predispose to arrhythmias. Vulnerability to PES, i.e., the induction of tachycardia, also will be discussed below. The Atrioventricular
Node (AVN)
The functional status of the AV node during sinus rhythm is estimated from the A-H interval, which normally ranges between 54 and 130 msec.
36
Eflect of Neurohumoral
JOHN
Influences
The function of the AV node is influenced strongly by sympathetic and parasympathetic tone. 24*25~‘47~148 Periods of Wenckebach seconddegree AV block, presumably at the AV node, have been described in normal medical students’4g and in athletes”’ and ascribed to increased parasympathetic tone, but more serious conduction disturbances may exist in some of these subjects.‘s’
D. FISHER
such as anxiety and hypotension. With pacing, the A-H interval prolongs, with 70% of normal adult subjects developing Wenckebach at the level of the AV node at rates lower than 190 bpm.*’ In children, the rate at which Wenckebath appears is considerably higher, over 200 bpm,‘53 but is still lower than the rate at which Wenckebach occurs with exercise. Taking two standard deviations from the mean as the normal range, some normal subjects may develop Wenckebach at rates barely over 100 bpm with atria1 pacing*’ (Figs. 5 and 6).
AV Node Conduction In animals, there is dual spread of excitation in the AV node from a posterior input via the crista terminalis, and an input anterior to the coronary sinus.“’ These may correspond to the inputs from the internodal tracts that are postulated to exist in humans.‘32T’33 The posterior tract enters lower in the node, accounting for shorter A-H times during left atria1 pacing and may result in partial AV node bypass (see below Lown-Ganong-Levine syndrome). The AV node has been divided into an AN zone between the atrium and the node; an N zone of the node proper, with slow response action potentials accounting for slow or decremental conduction; and an NH zone between the node and the His bundle.“* The AV node may be envisioned as a network of potential pathways with somewhat variable refractory periods and conduction properties. Excitation in the AN and N zones is not well synchronized but occurs over a broad front, though wavefronts resulting from anterior and posterior inputs ultimately merge to activate the central nodal area, resulting in synchronous activation in the NH zone.15* During retrograde conduction, the pattern is not exactly reversed, as the anterior area in the interatrial septum is depolarized before the crista terminalis.“’ Fundamental Difference Between A-H Intervals With Exercise and With Pacing With exercise there is little change in the P-R and A-H intervals due to a decrease in parasympathetic and an increase in sympathetic tone, allowing the AV node to cope with the increased number of stimuli reaching it. With incremental atria1 pacing, however, autonomic tone is changed only indirectly in response to factors
incremental
Atria1 Pacing
If one plots the A-H interval against the heart rate in normal subjects, a smoothly rising curve is inscribed. In patients with the Lown-GanongLevine syndrome (AV nodes bypass or enhanced AV node conduction), there may be little or no increase in the A-H interval with incremental pacing. In patients with dual AV node pathways, a sudden break in the curve may be observed as the refractory period of the fast pathway is reached and conduction shifts to the slower pathway. These abnormal situations will be described in greater detail in the sections below dealing with tachycardias. Conduction Velocity and Refractory the AV NodeIs
Periods in
In most tissues the refractory period shortens with decrease in basic cycle length (increase in heart rate), and conduction velocity is altered little. In the AV node, the relationships are more complex. Conduction velocity decreases with decreasing cycle length during atria1 pacing, resulting in A-H interval prolongation. At shorter pacing cycle lengths, the refractory period defined by atria1 extrastimuli is found to shorten, and a beat of a given prematurity is conducted more rapidly during basic pacing at faster rates. Rapid Prolonged Pacing Some diseases of the AV conduction system, such as Lev’s or Lenegre’s diseases, result in fixed abnormalities within the conduction system. Ischemic heart disease, on the other hand, may result in a more dynamic abnormality,ls5 and prolonged rapid pacing at rates suffi-
ELEClROPHYSlOLOGlC
37
TESTING
NSR
RATE 60-00
380
60360 340
70
39
70-80
29
80-90
15
go-100 TOTAL
320
N27
8 119
300 280 260 240
Fig. 5. The A-H interval during normal sinus rhythm and during high right atria1 pacing. This is based on 119 adult subjects without evidence of AV node disease on the peripheral ECG; with normal intervals on the baseline sinus rhythm His bundle electrogram; and without evidence of enhanced AV node conduction during atria1 pacing (unpublished data from our laboratory). On the ordinate is the A-H interval in msec. On the abscissa: on the left the A-H interval during normal sinus rhythm et rates between 60 and 100 bpm. In the center, the A-H interval of the total group with a mean heart rate of 72 bpm. On the right, effect of atrial pacing on the A-H interval. Five lines (solid, dashed, and dotted) represent the mean and +l end k2 SD.
220
I--
s 200
l--
LO 160 140
,--
120
I--
100
l--
-
80
I--
-
6C
l--
40
I--
20 l-1
5’0 NSR
7’6 100 RATE
cient to induce ischemia may unmask abnormalities otherwise hidden in the conduction system. Ventricular
TOTAL
80 ATRIAL
120 WCIW
RATE
100 (n=llQ)
200
pathways also can be diagnosed using incremental ventricular pacing.
Pacing
Retrograde conduction from ventricle to atrium does not occur in all normal subjects,64 but when present, utilizes the normal conduction pathway, including the AV node, in a retrograde fashion. With incremental ventricular pacing, the VA interval gradually prolongs, ultimately resulting in a Wenckebach. As with antegrade conduction, a smooth curve normally is inscribed, but flat curves (indicating some degree of AV node bypass) and dual AV node
Echo Beats The AV node is a network of potential pathways most of which have similar conduction and refractory characteristics in normal individuals. Nevertheless, a premature beat may find one pathway refractory so that the impulse travels antegradely down another pathway. Ultimately, the pathway that previously was refractory now conducts the impulse retrogradely into the atrium resulting in an AV nodal echo beat.
38
JOHN
D. FISHER
\ = Rate where this patient developed Wenckebach Meam154: 26 n= 118pts
80
60
I
80
I
I
I
I
120 160 ATRIAL PACING RATE
Pharmacology Medications such as edrophonium, proprano101, and verapamil depress AV node conduction (Table 1). Procainamide, quinidine, and disopyramide may depress conduction directly, but their vagolytic effects enhance conduction and the overall effect is unpredictable. Digitalis may depend on an intact vagal system for its depressant effect on the AV node. Isoproterenol and atropine directly facilitate AVN conduction. Chronic A V Node Block Congenital complete AV block typically occurs at the AV node.‘56 Many of these patients have reliable junctional rhythms and their growth and development may be normal. With exercise, junctional rates increase but not to a degree equivalent to that seen with conducted sinus rhythms. Cardiac output requirements must then be met with an increased stroke volume, and hence, cardiomegaly develops. Most physicians would opt for the implantation of a
I
I
200
I
I
220
Fig. 6. Atrial pacing at which Wenckebach at the A-H level develops in patients without evidence of AV node disease on the resting ECG or baseline His bundle electrograms (unpublished data from our laboratory). On the ordinate is the percentage of patients with normal AV conduction who develop Wenckebath at the AV node, and on the abscissa is the atrial pacing rate. We find it useful in preparing electrophysiologic reports to use this graph, with an arrow marking the point at which the individual undergoing studies developed Wenckebath. In this group of 118 adult subjects, Wenckebach developed at a mean rate of 164 f 26 ISD) bpm.
cardiac pacemaker at the point when either cardiomegaly or symptoms develop. An atria1 synchronous pacer (VAT; VDD) is especially physiologic in active subjects such as growing children. Junctional recovery times (JRT) have been reported, analogous to SNRTs, following atria1 or ventricular pacing.i5’ A corrected JRT (CJRT = JRT - basic cycle length) of 200 msec or less, either in baseline state or after 2-2.5 mg atropine, was typical of asymptomatic patients whether the junctional pacers were located in the AV node or bundle of His. Those with longer CJRTs may require pacing. Myocardial infarction and the AV node will be discussed in conjunction with the HisPurkinje system. Clinical Implications of AV Node Block or Disease Patients with AV node disease are at an increased risk of syncope’” and progression to
ELECTROPHYSIOLOGIC
39
TESTING
complete block, if not already present.151~‘58 Myocardial dysfunction is more likely to exist in combined AV node and bundle branch disease than in the latter alone.“’ Overall mortality is not high, however, with AV node block.15’ The His-Purkinje System (Infranodal Conduction, H-V Interval)
Incremental Atria1 Pacing With incremental atria1 pacing the H-V interval normally remains constant, with block or H-V prolongation representing a pathologic finding associated with subsequentdevelopment of AV block and sudden death.159As with the AV node, blockages in the His-Purkinje system also may be dynamic, especially if related to ischemia. Programmed Extrastimuli (PES) The H-V interval usually remains stable with increasingly premature PES, as the refractory period of the AV node is usually longer than that of the His-Purkinje system. The role of the His-Purkinje system in tachycardias has been studied using PES, as have antegrade and retrograde refractory periods and “gaps.” All these will be discussedbelow. Retrograde Conduction: Incremental Ventricular Pacing and PES’6G’62 The His bundle potential is difficult to record during retrograde conduction. Catheters with a very small interelectrode distance (1 or 2 mm) may increase the chances of recording a His bundle potential by increasing the localization of the recordings.“j’ Retrograde block is encountered commonly in the AV node, but delays in or below the His bundle also occur.16oRetrograde conduction is not predicted by the degree of integrity of anterograde conduction or by bundle branch block.16’With PES in the right ventricle, retroconduction usually is via the left bundle branch.16* Pharmacologic Agents and the His-Purkinje System Procainamide is the most useful agent presently available in the United States for stressing of the His-Purkinje system (Table 1). Intrave-
nous dosesof 10 mg/kg over 15 or 20 min may prolong the H-V interval in normal patients and cause rather striking prolongations in patients with bundle branch block.‘633’64 In somepatients with syncope or dizziness, procainamide may result in complete heart block at the H-V level. The Europeans report similar findings with ajmaline.j6’ Lidocaine, although rarely causing any H-V prolongation in normal subjects, may cause heart block at the H-V level in susceptible patients,‘66again typically those with symptoms and usually with bundle branch block. Because H-V block in responseto these medications is so clearly abnormal, implantation of a permanent pacemaker seems appropriate in symptomatic patients. Intra-Hisian Blocks (Split His Potentials)‘67-172 (Fig. 7) A block within the His bundle, reflecting very localized disease in the specialized tissue, is diagnosed by a broad multiphasic His bundle potential or two distinct His bundle potentials, both frequently accompanied by a normal QRS complex. Intra-Hisian block may be a particularly malignant condition, as transient heart block with a narrow QRS may be attributed to AV node diseaseand discounted. Carotid sinus massage often is revealing, with AV node Wenckebach worsening and intra-His or H-V block improving. Some consider a split His potential to be one of the few absolute indications for a permanent pacer on the basis of an electrophysiologic study, as most patients with split His potentials have had documented heart block or syncope.167-171 A recent report, however, has suggestedthat the prognosis of intra-Hisian diseasemay be more benign.“* A normal QRS in conjunction with a very long H-V interval also may represent balanced first-degree block within the bundle branches. Complete block of one bundle branch would still leave the other functioning. This may account for the more benign prognosisof somepatients who were felt to have intra-His block. In others, distal His bundle pacemakers may provide an adequate rate. A corrected junctional recovery time of 200 msec or lessmay save someasyptomatic patients from an implanted pacer.“’ There appears to be a predilection for split His potentials among elderly females,‘67.‘69 but it may be congenital or surgically induced.“’ Lidocaine and procain-
JOHN
A-A H-H’ WV
1306 8 50
1250 160 50
D. FISHER
X X
Fig. 7. Irma-His block produced by lidocaine. This elderly woman had a history of recurrent syncope and a normal electrocardiogram. Baseline electrophysiofogic recordings illustrated in the first panel, revealed the presence of a multiphasic or ragged His bundle potential. After the administration of 50 mg of lidocaine (middle panel), there was little change in the heart rate (AA interval). but the multiphasic His bundle potential has now split into two positions. In the third panel, following an additional 25 mg of lidocaine, there is complete heart block at the intra-His level. Such sensitivity to lidocaine is uncommon even in people with advanced His-Purkinje disease, but illustrates the need for caution in people with a history of unexplained syncope. While the AV node is the usual site of block in patients with a narrow QRS interval, the presence and potential malignancy of intra-His block should be considered strongly in patients with a history of syncope.
amide commonly produce complete block in this condition (unpublished observations) (Fig. 7). The Clinical Significance
of the H-V Interval
The clinical significance of a prolonged H-V interval is still a matter of lively dispute. Asymptomatic patients with very long H-V intervals are reported to enjoy a favorable prognosis,‘73 although longer follow-up periods are beginning to revise this impression.174 The clinician frequently must deal with the problem of a patient with syncope or near syncope in whom complete medical and neurologic evaluation, including ambulatory ECG monitoring, has failed to reveal a cause for the symptoms. The role of the H-V interval has been difficult to resolve because most studies have included all patients with bundle branch block even if asymptomatic.‘73-‘82 Other problems are generated by the inclusion of patients who may be symptomatic but have known prior intermittent heart block or other causes for symptoms such as sinoatrial disease or tachycardias.‘83*‘84 Few have assessed the role of permanent pacing in patients suspected of having intermittent heart block on the basis of a prolonged H-V interval. In one study,‘85 59 consecutive patients had symptoms suggestive of intermittent heart block, unrevealing medical and neurologic evaluations and
ambulatory monitoring, and His bundle studies that were normal {in one-third of the patients) or showed only a prolonged H-V interval. Half of the patients with long H-V intervals received permanent pacers. Progression to heart block did not occur among patients with normal H-V intervals. Among patients with prolonged H-V intervals, heart block was documented during follow-up in 25%; however, among the unpaced patients, progression to heart block was accompanied by recurrent symptoms, whereas in the paced patients, it was observed only as an incidental finding during pacemaker check-ups. Sudden death occurred only among unpaced patients in the long H-V group. By decreasing the number of variables, His bundle studies seemed to suggest that permanent pacing is appropriate for symptomatic patients with H-V intervals of 60 msec or more, in whom other causes for syncope are not apparent. Bundle Branch Block, Prolonged P-R Interval and the His-Purkinje System: Additional Considerations Based on electrocardiographic data alone, the overall risk of development of complete heart block in patients with bifascicular block appears to be less than 7%10% per year in hospitalized or cardiac patients, and much lower in asympto-
ELECTROPHYSlOLOGlC
41
TESTING
matic patients.‘86-‘89 Attempts to correlate the H-V interval with the peripheral ECG configuration have proved of statistical interest, but of little use for the individual patient. A prolonged H-V interval can be observed in patients with normal QRS complexes’85 and is the rule in patients with right or left bundle branch block combined with left axis deviation.‘903’9’ About one-quarter of patients with right bundle branch block will have prolongation of the H-V interva1,19’ but the incidence rises to 40%-70% when right bundle branch block is combined with left axis deviation and 66%-100% in right bundle branch block plus right axis deviation.‘9”92 Twothirds of patients with left bundle branch block may have a prolonged H-V interval.19* There is some question whether ventricular activation occurs later in isolated left bundle branch block compared to right bundle branch block.‘933’94 Although the addition of a first-degree AV block increases the likelihood of H-V interval prolongation in both right and left bundle branch block, more than a quarter of patients with any combination of “incompIete trifascicular block” will be found to have a normal H-V interval.19* Pseudo-complete bundle branch block has been described in which spontaneousor induced block of the other bundle reveals conduction through the supposedly blocked bundle, indicating that the “complete” block was, in fact, only firstdegree block.‘95The presenceof alternating right and left bundle branch block implies diffuse conduction system disease and most such patients probably should receive permanent pacemakers. Rate-dependent bundle branch block often is associated with cardiac disease’96 but most do not require permanent pacing.
Conduction System in Acute Myocardial Infarction Following acute myocardial infarction, highdegree AV block, new bundle branch block, or a prolonged H-V interval are associated with an unfavorable prognosis.‘97m2’2 It is not clear, however, whether permanent pacing would prevent subsequent mortality in these patients, which often is due to ventricular tachycardia, fibrillation, or pump failure as well as heart block. In some subjects, a repeat His bundle study performed just prior to discharge home
may reveal a return towards normal of the H-V interval, and this is associatedwith an improved prognosis.209Solitary left anterior hemiblock does not have a deleterious effect on prognosis*” but it may obscure concurrent RBBB unless unipolar V-leads are placed higher than usual and right chest leads are recorded.2’412’5 With an inferior wall infarction, left anterior hemiblock itself may be obscured but can be diagnosed by the presence of a terminal S in lead II and a terminal positive deflection in AVR.2’6 Inferior wall myocardial infarctions are classically associated with block at the AV node that usually is transient; anterior wall infarctions result in a more sudden and permanent block in the HisPurkinje system.*” Electrophysiologic studies during the course of acute myocardial infarction often reveals, however, that diseaseis more widespread and even in a different location than suggested by the electrocardiogram: sinus and AV node diseaseare not uncommon with anterior wall myocardial infarctions and H-V prolongation or intra-Hisian blocks are not unusual with inferior wall myocardial infarction. 2'7-220 Most current guidelines for implantation of a permanent pacemaker following acute myocardial infarction are derived from series using surface ECG data.
Multilevel Disease’.22’ Because of the high incidence of multilevel disease,atria1 pacing may not be appropriate for all patients with sinus nodedisease,although it is more desirable physiologically. Before permanent atria1 pacing is undertaken as treatment for the sick sinussyndrome, the physician should be satisfied that there is no significant conduction system disease. Concurrent diseaseof the AV node and HisPurkinje system is common. The combination of right bundle branch block, left anterior fascicle block, and first-degree AV block may not represent “trifascicular” disease at all: delay also could originate within the atrium or the AV node; or, because of longitudinal dissociation, the His bundle alone may be the site of apparent trifascicular disease. Intraatrial conduction delays may result in first-degree AV block and higher degrees of
42
intraatrial block may mimic peripheral cardiogram.
JOHN
AV block on the
Electrophysiologic Characteristics of Miscellaneous Diseases and Conditions Aortic valve disease.222*223 Aortic insufficiency and aortic stenosis may be associated with complete heart block. Block at the AV node is more common with aortic insufficiency, and block in or below the His bundle with aortic stenosis. Mitral valve prolapse.224S225 Mitral valve prolapse is associated with cardiac arrhythmias, including variations in the sick sinus syndrome and ventricular tachycardias (typically originating in the papillary muscles), which may account for the incidence of sudden death with this condition. Hypertrophic cardiomyopathy.226v227 Electrophysiologic testing in six patients with this condition revealed a normal A-H interval in all and a prolonged H-V interval of 60 msec in one patient.226 Heart block is not rare in this condition.==’ Congestive cardiomyopathy. H-V interval prolongation is common in congestive cardiomyopathy, especially in the presence of bundle branch block.22s The presence of conduction disease is not correlated with the degree of ventricular enlargement or end-diastolic pressure. Conduction abnormalities also are seen in alcoholic cardiomyopathy, with H-V interval prolongation again being more common than disease of the AV node.229 Infiltrative cardiomyopathy: Sarcoidosis, amyloidosis, and hemochromatosis.230*23’ Atria1 and ventricular tachycardias, sinus node disease, and heart block occur with unfortunate frequency in these conditions. His bundle studies may reveal abnormal sinus function tests as well as prolongation of the A-H and H-V intervals. Collagen-vascular diseases.232-234 As with the infiltrative cardiomyopathies, heart block and other arrhythmias may occur with collagen vascular diseases, particularly systemic lupus erythematosis. Congential complete heart block appears to be particularly common in newborns whose mothers have connective tissue disease. Infectious processes. Viral myocarditis may be associated with ventricular arrhythmias. Recovery from varicella myocarditis is uncom-
D. FISHER
mon, perhaps due to malignant ventricular tachycardias and fibrillation, although successful treatment of a case with mexiletine has been reported.*” Bacteremias also may result in heart block. Electrophysiologic studies on one 18-yrold girl with gonococcal septicemia revealed both intra- and infra-His bundle block, which persisted on restudy 6 mo after the acute episode.236 Chagas disease is a common cause of heart block and tachycardias in South America 237.238 Thyroid disease. Sudden death, ventricular arrhythmias, heart block, and myocardial infarction all have been reported with thyrotoxicosis. In one patient, ventricular fibrillation was precipitated by coronary artery spasm; both were eliminated after she become euthyroid.239 Although block has been described, facilitation of AV conduction appears more commonly in hyperthyroidism. In patients with hypothyroidism, AV block may be localized to both the AV node and His-Purkinje system and the myocardial action potential duration is prolonged.2N The Ventricle
Ventricular pacing is used to test the retrograde conduction system, to produce ischemia by prolonged pacing as described above, and to establish refractory periods and sequence of depolarization during tachycardias, as will be described below. Refractory Periods (Fig. 8) Several different refractory periods are defined by extrastimuli given with increasing prematurity until the stimulated tissue becomes unresponsive. Incremental or slow incremental ramp pacing also may be usedto estimate refractory periods, with the pacing rate increased until noncapture occurs. S 1Sl refers to the baseline spontaneous or paced cycle length and SlS2 is the interval from the last baseline beat to the premature extrastimulus (S2). In the atrium, SIS2S.. . may be designated A 1A2A . . . ; ventricular beats may be labeled VIV2V . . . , etc. By convention, refractory periods are generally measured with low pacemaker stimulation amplitudes, usually 2-4 times threshold. This convention will be assumedexcept where noted below, although reproducibility is enhanced if test stimuli are more than twice threshold.24’
ELECTROPHYSlOLOGlC
AV CONDUCTION Al ATRIUM
43
TESTING
!XiTEM
REFfUCTORY A3
Al
n
/\
PERKIDS
ERP
FRP
n -
ERP AVN
/\
n II
II
Ii1
Hl
FRP
II1
n III
Hz
H3
FRP AV Vl
Vl
V2
v3
FRP HIS-BB ERP Fig. 8. AV conduction system refractory periods: schematic (see text). Al. baseline atrial beet (spontaneous or paced); A2, programmed extrastimulus: A3, recovery beat. Hl, H2. H3, Vl , V2 and V3 are, respectively, His bundle end ventricular complexes following the appropriate atrial beat. ERP, effective refractory period: the longest SlS2 (here Al AZ) that does not conduct. In this illustration the alternative end virtually identical definition is used: the shortest Al Al resulting in conduction. FRP, functional refractory period: The shortest possible response to an SlS2 (here AlA2). At each level in the conduction system, the ERP may be considered as a stimulus-to-stimulus interval and the FRP es a response-to-response interval. As noted in the text. atrial refractory periods often include intraatrial conduction times, so that the ERP and FRP are identical only when stimulation end recording are performed at the same site, and there is no latency between stimulus and response.
The absolute refractory period is reached when SlS2 shortens to the point where S2 fails to evoke a responseno matter what the stimulus amplitude. The eaective refractory period (ERP) is usually measuredwith the stimulus at 2-4 times threshold, and is the longest SlS2 that does not produce a depolarization. For the atrium, the ERP may be measured directly from the SlS2 (AlA2). The ERP of the AV node is the longest AlA that does not give rise to a His bundle depolarization. The ERP of the total AV conduction system occurs when Al A2 fails to produce a V2. The ERP of a given bundle branch is the longest interval between two successive His bundle activations (SlS2 here, actually H 1H2) resulting in bundle branch block (see Fig. 8).
The functional refractory period (FRP) is the shortest possibleresponseto an SlS2. Thus, for a given site in the atrium, the FRP may be identical with the ERP unlessthere is a latent period between stimulus and response.Atria1 FRPs are often reported with high right atria1 stimulation and low atria1 response,so that ERP and FRP will differ. For the AV node, the FRP is the shortest interval between two His bundle depolarizations (HlH2) that could be produced by any SlS2 in the atrium (Fig. 8). Ultimately, the longest SlS2 that does not produce a response must virtually equal the shortest SlS2 that does produce a response. Some investigators therefore report the ERP as the shortest SlS2 resulting in a response. It is helpful to consider the ERP as a paced or tissue stimulus-to-stimulus measurement and the FRP as a response-to-responsemeasurement. Thus, the ERP of the AV node is defined in terms of atria1 stimulation, and the FRP of the AV node is defined in terms of the resultant His bundle depolarizations. The relative refractory period (RRP) is the longest SlS2 at which measurable conduction delay appears. For the AV node, this occurs when the A-H following S2 is longer than the A-H following Sl. Interpretation of refractory periods (Table Refractory periods are influenced by 51.2423243 many factors, thereby complicating the assessment of their significance. The refractory periodsof the AV node increasewith age to a greater extent than in other parts of the conduction system. Marked prolongations in the refractory period beyond the normal ranges may be observed but are not commonly used as a basis for a decision regarding permanent pacing. Analysis of refractory periods has helped in the understanding of reentrant arrhythmias, to be discussedlater. The Action Potential: Fast and Slow Responses (Fig. 9) A number of ionic channels have been identified and characterized in cardiac cells. These channels are said to be either “fast” or “slow” depending on the speed with which ions are transported, especially in depolarization of the cell. Compared to those using the fast channels, cells depolarizing via the slow channels have a
44
JOHN
Table
5.
Normal
Refractory
Periods
at Various
Cycle
Lengths’-
Adults
Children
ERP ” CL:
Longest
arsuring
Atrisl
FRP SD
+2s!3
n
Mean
(7 mo-
15 yrl
HIP SD
t2SD
n
FRP
Mea”
SD
+2sJ
n
Mean
SD
Captue+
Atrium A”
Mean
D. FISHER
node
7.6
236.
49
334
26
274.
47
366
40
167.
53
293
35
217‘
46
269.
44
377
406’ -
46
496
40
241*
56
353
15561
45 -
-
-
11
36 -
345. -
10
A96
5
412.
72
LB9
2
473
67
16071
-
-
9
323.
39
401
361
52
(4651
206
60
366
6
247
53
303
61 -
1465) -
6 -
427 -
74 -
-
-
CL: 650-600 Atrium
26
232
60
392
26
275
49
373
AV node
26
290
60
390
401 -
46
(525)
26 -
-
497 -
(552)
-
-
-
RBS
4
443
LB6
4
434
42 59
-
6 1 6
390 404
31
(466)
-
CL: 599-460 AtrWnl A”
node
30
232.
54
340
30
271.
49
369
37
199.
43
265
34
234.
43
30
326*
56
440
260.
55
370
10
365
35
435
37 -
354. -
66 -
365
423. -
520 -
37
26 -
406. -
57
367
29 -
61
(4921
-
RSB
6
LB6
CL:
-
6
370
459-260 Atrium
23
199.
26
255
23
252.
34
320
57
165.
37
239
54
200.
35
A”ti
16
260.
52
364
13
345.
27
399
55
219.
45
309
49
299.
46
RBB
4
16 -
13601 -
-
22
298
26
354
0
328 -
-
LB6
330
34
398
+Loneest
l
1
-
P < 0.05
CL assuin9 between
atrial adult
rspf~e: and
pediatric
696
t
107
for
adults,
535
+ 69
fa
-
12
children.
values.
less negative resting membrane potential, a lower amplitude of the action potential, a lower dV/dt resulting in markedly slower conduction velocity, and a longer refractory period. Phase 3 and 4 Blocks24”247 Phase 3 block (tachycardia-dependent block) occurs when an impulse arrives at tissues that are still in the refractory period. Phase 4 block (bradycardia-dependent block) occurs when the conduction of an impulse is blocked, for a variety of reasons, in tissues that are well beyond their refractory periods. The Gap Phenomenon244*24s-2s3(Fig. 10) During assessment of refractory periods using the atria1 extrastimulus technique, AV block may occur at a certain interval, but conduction may resume, after the gap, with further prematurity of the extrastimulus. There now appear to be at least six types of “gap” in AV conduction. For this discussion, Al is a beat of the basic atria1 cycle length. H 1 is the His potential resulting from an A 1. Dl is a distal Purkinje fiber or bundle branch depolarization resulting from H 1, and Vl is the ventricular depolarization resulting from Dl. These same letters followed by
number 2 are potentials in response to a premature atria1 beat. Each of the first three types of gaps occur at the H-V level, i.e., a His bundle potential is not followed by a ventricular depolarization. Type I gap. AV conduction is resumed because with increasing prematurity of A2 the A-H interval prolongs further so that Hl H2 now exceeds the refractory period of the His bundle and conduction resumes. Type II gap. Conduction resumes because increasing delay in the proximal His-Purkinje system results in a DlD2 exceeding the refractory period of the distal conducting system. Because the refractory periods in the distal conduction system are rarely symmetrical, conduction typically resumes with an aberrant QRS and a prolonged H-V interval. Type ZZZ gap. Conduction is resumed in spite of a shorter H 1H2 then was present at the time of block. Supernormal conduction, varying pulsatile vagal discharges, and a decrease in phase IV diastolic depolarizations have all been offered as possible explanations for type III gap, but the real mechanism or mechanisms remain a mystery. Type ZV, V, and W gap. These less
ELECTROPHYSIOLOGIC
TESTING
SLOW RESPONSE
FAST RESPONSE
-60 -8ON
1 @‘:uJih 1 ERP .a J-“(
l
A)
1 m+ . -
r::- - - - -- ,---A ------(WRESTING MEMBRANE) f Po&JLATED IAL (RflP) / ( PROTECTION ---I
FAST RESPONSE IMPULSE
ERP = EFFECTIVE REFRACTORY SNP = SUPERNORMAL PERIOD
PERIOD
SLOW RESPONSE
PROPAGATION
-CONDUCTION VELOCITY0.5 - 3 fl/SEC -SAFETY FACTOR (ABILITY TO -HIGH PROPAGATE TO NEXT CELL>
0.005
TO 0,1
!/SEC
Low
Fig. 9. The action potential: slow and fast response. See the text and references 71,256, and 257. The left-hand panel shows the fast response action potential characteristic of working myocardium and of Purkinje fibers, and the right-hand panel shows the slow response action potential seen in the sinus node, portions of the AV node, in diseased or altered working myocardium and Purkinje fibers. On reaching threshold, the upstroke of the action potential begins, moving the membrane potential from negative towards positive. The slope of this depolarization is expressed in terms of the change in voltage divided by the change in time and is directly proportional to conduction velocity within a given cardiac tissue. The dV/dt is considerably greater in fast response than in slow response cells. The fast response cells undergo a rapid, brief, and partial repolarization (phase 1). a relative plateau (phase 2). followed by repolarization with return to the resting membrane potential (phase 3). Slow response cells lack a phase 1. Following return to the resting membrane potential, the cell enters phase 4, generally equivalent to diastole, until the next depolarization. During phase 4, working myocardial cells maintain a constant membrane potential, but cells with pacemaker (automatic) activity gradually depolarize until the threshold potential is reached and another action potential is generated. In fast response cells, the effective refractory period (ERP) lasts until sometime during phase 3. In contrast, the effective refractory period of slow response cells may exceed the action potential duration. Other characteristics of the action potential are outlined in the illustration.
commonly encountered gaps have their initial blocks, respectively, at the distal AV node, the His-Purkinje system or AV node and the HisPurkinje system; the respective sites of proximal delay allowing resumption of conduction are in the proximal AV node, the atrium, and nowhere (supernormality). Interpretation and signijicance of the gap phenomenon. The gap phenomenon is not an abnormality but is primarily a reflection of the interplay between the conduction velocities and refractory periods of the different parts of the conducting system. Changes in neurohumoral influences or heart rate will, therefore, alter one’s ability to demonstrate the Gap Phenomenon in any given patient.“’ Gap phenomena in retrograde (V-A) conduction”’ and in intraatrial conduction2s2~2s3 analo-
gous to those seen in the antegrade conduction system have been described.
Supernormal conduction exists when a precisely timed beat results in restoration or improvement of conduction, especially in a previously depressed or blocked area. Supernormal excitability typically occurs just at the end of phase 3 of the action potential, and exists when there is excitation by stimuli that are subthreshold at any other point in the cardiac cycle. Clinically, supernormal excitability may be observed when a failing artificial pacemaker is able to capture only when its stimulus occurs at the end of the T wave. It is generally agreed that supernormality can occur in the HisPurkinje system, Bachman’s bundle in the dog,
46
JOHN
D. FISHER
GAP PHENOMENON HI
Dl “’
Late A2 z
I
aEarly A2 ~ (A-l/ Block)
I
0
A2
D?
Hz
A
I
AzHz
H+ti
)AlHt
@
))AIHI
(@
REASON FOR RESUMED CONDUCTION
A2
A A2
@GEE-: A
I
A
I
))))A1 HI ha
I
t AVN Delay :.tAzHz :. HlHz)H-RP t Proximal
III
A
I
A
A
)))AlHl
(0
y-7; Elay :.D& )RP ?Super Normal ?AVagal Tone ? i Phase 4 Block
Fig. 10. The gap phenomenon. Gap types I, II, and Ill in AV conduction are outlined (see text). Al, Hl , Dl, and Vl indicate, respectively, baseline atrial, His bundle, distal His-Purkinje system, and ventricular depolarizations. A2 represents an atrial premature beat with H2. D2, and V2 following when possible. In the top line, an atrial premature beat is conducted with a prolonged A2H2 interval. In the second line the A2 is followed by further prolongation of the A2H2 and subsequent block. In the third. fourth, and fifth lines, conduction is restored by further prematurity of A2 in the patterns of types I. II, and Ill gap. Explanations are provided in the key to the right of each line.
and probably in the working myocardium of the atrium and ventricle, but not in the AV node.
“slow response” not only make reentry possible, but are also related to an abnormal type of “triggered” automaticity.
Induction of Tachycardia
During the performance of electrophysiologic studies, incremental, ramp, or burst pacing, or programmed extrastimuli may result in the induction of tachycardias. The analysis and interpretation of such tachycardias is covered in the next section. TACHYCARDIAS
Mechanisms
of Tachycardias7’G256C257
An extensive critical review of the postulated mechanisms responsible for tachycardias is beyond the scope of this survey. Some of the basic tenets will be introduced briefly as background for subsequent discussions. Automaticity, conduction velocity, and the refractory period are prime determinants of the behavior of cardiac tissues. Tachycardias may be due either to an increase in automaticity or to a change in the relationship between conduction velocity and refractory periods that results in continuous propagation of an impulse, i.e., reentrant tachycardia. There are many variations on these themes, and phenomena related to the
Automaticity
Automaticity may be defined as spontaneous phase 4 depolarization ultimately reaching the threshold potential with generation of an action potential. The rate (frequency) will be increased if any of the following occur: a decrease in the action potential duration, an increase in the steepness of phase 4 depolarization, a less negative resting membrane potential, or a more negative threshold potential. Overdrive suppression.258S25g Upon cessation of rapid pacing or intrinsic rhythm from another site, an automatic focus will not return immediately to its baseline rate. Rather, there will be a pause followed by a gradual return to the baseline rate. Effect of premature beats on automatic rhythms. Suitably timed premature beats can
depolarize an automatic focus unless it is “protected” (see below) and, therefore, reset the timing of the automatic focus. Premature beats have inconsequential effects on the intrinsic rate of firing of automatic foci. Overdrive excitation.258 Purkinje cells stud-
ELECTROPHYSIOLOGIC
47
TESTING
ied in vitro and subjected to catecholamines may exhibit excitation or acceleration rather than suppression following overdrive pacing. Relatively slow pacing may be followed by extrasystoles or minimally accelerated automatic firing. Faster pacing for brief periods may result in automatic rhythms that are slower, similar to, or even faster than the paced rate. Prolonged pacing of such tissues, however, generally results in overdrive suppression. The role played by this mechanism in clinical arrhythmias is not yet defined. Triggered automaticity.259~260 Slow response cells may have one or more oscillatory afterpotentials following repolarization. The amplitude of the afterpotential may be increased by catecholamines and by pacing or premature beats. The afterpotential may reach the threshold for activation, and the ensuing action potential may be followed by an afterpotential, which itself reaches the threshold for activation initiating a sustained accelerated rhythm. Sustained rhythmic activity can also be terminated by a premature beat. Protection and entry block.256s26’*262 Automatic rhythms may continue to depolarize with the timing unaffected by spontaneous or induced beats from other sites. At least six mechanisms have been proposed to explain such protection: (1) a very rapid rate (short cycle length would render the focus almost continuously refractory); (2) the threshold potential of the parasystolic focus might be so high (less negative) that impulses from the surrounding tissue would be unable to bring it to threshold; (3) the refractory period of the parasystolic focus might be so long as to occupy much of diastole; (4) phase 4 depolarization of cells surrounding the parasystolic focus; (5) a protection potential has been proposed262 that is a variant on the theme of phase 4 block-when a cell depolarizes to its protection potential during phase 4 it may continue its spontaneous depolarization to reach threshold, but is impervious to external stimuli; and (6) unidirectional block as commonly observed in reentrant tachycardias (see below).
During normal rhythm the heart is sequentially activated by an advancing wavefront of depolarization that is extinguished when all accessible areas of the myocardium have been
depolarized. The heart then awaits the next impulse from the sinus node. Reentry occurs when an impulse, instead of being extinguished, contrives to exist in a cardiac backwater for a period sufficient to allow the rest of the myocardium to repolarize, at which point the persisting impulse reenters the myocardium, depolarizing it. The depressed area harboring the impulse that is to reenter the remaining myocardium is usually populated by slow response cells capable of slow conduction and may occur in areas surrounding fibrosis or infarction in atria1 or ventricular tissues, especially subendocardial Purkinje fibers, as well as in the sinoatrial and atrioventricular nodes. Two conditions, therefore, are required for reentry to occur: (1) unidirectional block, and (2) an area of slow conduction so that the impulse can survive until the cells in front of it are no longer refractory. Because refractory periods shorten with decrease in cycle length and conduction velocities decrease when depolarization occurs during the relative refractory period, two or three critically timed premature beats may be required to adjust the conduction velocities and refractory periods so that termination of a reentrant tachycardia occurs. Summation.7’~256 Summation occurs when the combined effects of two impulses result in conduction through tissues that could not be excited by either impulse individually. Impulses that might require summation for propagation because of a low safety factor for conduction are characteristic of slow response cells and may occur in the AV node and in depressed areas elsewhere in the heart. Anatomical arrangements that permit summation of impulses in one direction, but not the other, in effect create unidirectional block, which is one of the cornerstones of reentry. Overview on Tachycardia
Mechanisms
A few years ago it was thought that clinically useful tests existed that could separate reentrant from automatic tachycardias. Reentry tachycardias were thought to be characterized by reproducible initiation and termination by critically timed programmed extrasystoles (PES). PES that did not terminate the tachycardia often resulted in a pause that was less than compensatory, presumably because the reentrant circuit had been entered by the premature beat. This
40
JOHN
last criteria for reentry was the first to go. Premature beats during normal sinus rhythm also result in pauses that are less than compensatory. With the identification of triggered automaticity initiated and terminated by PES, each of the classic criteria for the electrophysiologic diagnosis of reentry thus have been found compatible with automaticity. The clinical cardiologist, therefore, is unable to state with certainty whether most tachycardias are due to reentry or to automaticity, especially of the triggered type. Nevertheless, most workers subscribe to the convention defining reentrant arrhythmias as those that can be initiated and terminated reproducibly by programmed extrastimuli in a well defined zone. Electrophysiologic Techniques
Study
of Tachycardias:
Techniques used in the study of tachycardias are the same as used in studies of the impulse formation and conduction system. These include programmed extrastimuli, rapid pacing, physical maneuvers including exercise and carotid sinus massage,pharmacologic agents, and psychologic stresses. In general, a well done electrophysiologic study will include programmed stimulation and incremental or ramp pacing from several sites in the atrium and the ventricle. When the endocardial recording sites are carefully chosen, these techniques will provide the bulk of the data required for accurate analysis of both the conduction system and tachycardias. Pharmacologic Agents Regrettably, it is not yet possible to select an effective treatment for every patient basedsolely on knowledge of the mechanism of the tachycardia. Characteristic responses to some drugs, however, may permit a more definitive diagnosis of the mechanismof a given tachycardia. Candidatesfor Electrophysiologic Studies of Tachycardias Studies performed specifically to aid in the therapy of the patient are appropriate when tachycardias are frequent, life-threatening, recurrent, unresponsive to conventional drug therapy, or are a psychologic burden to the patient.
D. FISHER
The technique of serial electrophysiologic testing is an efficient means of establishing the most effective pharmacologic or pacemaker therapy (seelater section). Electrophysiologic studies are also useful both during and in laying the groundwork for antitachycardia surgery. Electrophysiologic testing is beginning to play an important role in the identification and treatment of patients at risk of sudden death. Mappin?’ “Mapping” is the useof recordings or stimulation at a sufficiently large number of sites to permit accurate localization of initial and/or sequential depolarization. Epicardial mapping during tachycardia. At the time of open heart surgery, the time of depolarization at each of a large number of sites is determined and compared to a reference lead. Epicardial mapping has proven useful in localizing tachycardias with initial depolarization in the free wall of the atrium or ventricle. With atria1 pacing, epicardial mapping also can reveal the site of early ventricular activation by an anomalous atrioventricular pathway such as a Kent bundle. The technique is not without its limitations: 264the site of epicardial activation may be several centimeters distant from an actual endocardial focus; epicardial mapping cannot localize accurately tachycardias originating in the septum. The epicardial surface usually can be mapped in approximately 10-l 5 min by experienced personnel using a mobile hand-held probe. The use of a “sock” pulled over the heart with many built-in leads that can record simultaneously, allows computer-assisted mapping of a single beat.265 Endocardial mapping (passive observation from multiple sites).266 During electrophysiologic studies, some insight into the depolarization sequence can be gleaned from stationary well sited leads. More precise information requires a mobile catheter lead. At the time of open heart surgery, endocardial mapping can be done more precisely and permits localization of arrhythmias arising in the endocardium or the septum. Pace mapping (active stimulation from multiple sites).267 Epicardial or endocardial pacing can mimick the QRS configuration of a tachycardia if the stimuli are delivered close to the
ELECTROPHYSIOLOGIC
49
TESTING
focus or point of earliest activation. Changes in pacing site change the QRS configuration, and preliminary surgical experience confirms that good localization of the tachycardia is possible using pace mapping. The ultimate role of this technique is not yet defined. Electrophysiologic Tachycardias
Characteristics
of Specific
Supraventricular Tachycardias (Table 6, Figs. 11 andI2) Definitions and general considerations. The term “paroxysmal atria1 tachycardia” (PAT) generally has fallen out of favor, being replaced by the lessspecific term paroxysmal supraventricular tachycardia (PSVT). Included within the scopeof PSVT is a constellation of arrhythmias within which true atria1 tachycardia plays a
“SVT”
relatively small role. More commonly, PSVT results from abnormalities in the AV node, one of the overt or concealed preexcitation syndromes, or even to abnormalities of the sinus node. Several factors are considered in the differential diagnosis of PSVT. (Many of these will be discussedfurther in the context of specific tachycardias.) (1) Response to programmed extrastimuli: reproducible initiation and termination of the tachycardia by programmed extrastimuli within well defined tachycardia initiation and termination zones suggests the clinical diagnosis of a reentry mechanism in spite of awarenessof the existence of triggered automaticity. (2) Additional responses to pacing or programmed stimuli: this is observed if the ECG
TYPES
Fig. 11. Types of supraventricular tachycardia (see text). “Circuit diagrams” outlining the mechanisms of tachycardia. During tachycardia, strategic placement of recording electrodes would allow sequential mapping of depolarizetion, which, in many cases, would be sufficient to identify the type of tachycardia. Abbreviations (see text): AAT, automatic atrial tachycardia; AcAVNT, accessory AV nodal tachycardia: AFL, atrial flutter; AN-JT junctional tachycardia arising at the AN region of the AV junction; AVNCT, AV nodal conduction tachycardia; AVNRT, AV nodal reentrant tachycardia; Cone WPW, concealed WPW syndrome; CNPSNT, chronic non-paroxysmal sinus node tachycardia; HBT, His bundle tachycardia: James, tachycardia related to en atrial-His bypass tract; LGL. Lawn-Ganong-Levine syndrome; Mahaim. tachycardias related to nodal-ventricular, or fasciculoventricular fibers: NH-JT. junctional tachycerdia arising at the NH region of the AV junction: NSR, normal sinus rhythm: “PAT,” paroxysmal trial tachycardia; SANRT. sinoatrial nodal reentrant tachycardia; WPW, Wolff-Parkinson-White syndrome; RA, right atrium: RV. right ventricle; LA, left atrium: LV, left ventricle.
50
JOHN
Table
6.
Typical
Findings
Characterizing
SANRT
ECG
h
SVTI
Pas
NSR: often
Types
CNPSNT
rate
wide
R-P
duration
Brief
LOIt
Across
Facing
AAT
P-variable
range
Pages)
Flutt0l
P-variable
AVNRT
“Sawtooth”
aften
Ps
AVNCT
P in or neaf
COmlllO”
ClRS.
‘k of R-R
beyond Epcxde
(Reed
PAT
Ps 8% NSR;
rate slow
of SVT
D. FISHER
often
P nnvarted
rreg.
PwNSR
m II, 111, AVF
Varies
Parox
w
Varies
Par01
a
“pftrm”
Varies
-perId Induce
and
terminate
WlIh
PES
Yes
NO
YES
Unusual
Rare
Yes
7
Whh
b”rst/wer#w
YeS
NOhare
Yes
Un”S”fil
Yes
Yes
7
Effect
of BBB
Effect
of wagal
on rate tone
None
Nom
Marked
same
NCWld
NCSllM,
cases
slow
None
NOW
NOW
None
NOW
VWiS
LIttIe
Little--may
Significant
?
NWlTld
Normal
NO,lW
cause A-H
curve
with
At.
pace
or PES
AVB “Break”
due
dual V-A
curve
with
V-pace
(x PES
NO,ltld
NWIW
NCSKd
Normal
NCNltld
“Break”
due
dual 1:t
AVratio
Atrlal
*
d+olarization
wth
seq”mc*
as NSR/normal
as NSRlnwmal
varies
tachylV-stim
among
Rare
“S”d
Varies
Complex
HBE
to
“srealr”
to
V-A
paths block
paths 1:2AV. area
first
etc.
as NSR/namal
indiwduals
H-V in NSR
NGiltMl
NLVltXll
NCSllld
Normal
Normal
Normal
N-Xltld
I” ,ach
Namd
NO,ld
NWTIA
NOrI
NWttMl
NDrlM
NLTl3l~l
NO
NO
NO
NO
NO
NCI
NO
Normal
Normal
NC#llMl
NCXmd
Atrium
peexcited
when ECG
His
by VPES
refractay
(in NW
Nwmal
COmlll*“tS
SNRT.
Nwmal SACT
usually Effectwe
Rx*
Asrociated
2 groups:
nwma,
responds
dseease
Most to P D.Q
NO
NO
f- Normal
PR
common
PSVl
P
0.V hsin
1
pacing
P,DPH
Yes
YES. esp.
pacing.
DC
be
text1
CV
P.D.PA.0
7
+
7
cnikken AAT.
automatic
tachycadia; length;
atria,
AVNRT. HgE.
progammed *Effective
low
tachycadia:
AV right
node
atrium
extrastim”Ii;
0.
treatment.
Drugs
AcAVNT, reentry
tachycad+a;
recaded
on His
quinidine; listed
accessay
bundle
currently
bundle
node
tzxhycardia:
branch
ektrogam;
v. verapatti,: are
AV
BBS,
a
block:
Kent,
V-A
ewe.
plot
soon
to be available
Kent
ventricle
AN,NHT,
tachycardia
CNPSNT.
chronic
bundle:
D. digitalis:
to atrium
in USA.
See
at atriwvxlal ncqxroxysmal DC CV.
conduction text
complex during pacing at the same rate as the tachycardia is similar and there are changes with alterations in the pacing site. Of particular importance is the shape of the A-H curve with increasing heart rate. In contrast to the normal gradual increase in A-H interval with increasing heart rate or prematurity of the programmed extrastimulus, characteristic changes occur with supraventricular tachycardias involving the AV conduction system (Fig. 12). (3) The site of origin and sequence of atria1 activation: it is unlikely that the sinus node is responsible for a tachycardia with initial depolarization in the distal reaches of the left atrium. (4) Important clues from the ECG:268 (A) AV nodal reentrant tachycardia is suggested by simultaneous atria1 and ventricular activation. (B) Inverted P waves in the inferior leads and an R-P interval less than one-half the R-R interval occur in 30% of patients with AV nodal reentrant tachycardias and in virtually all patients
and
time Table
1 fw
or nodal-His sm”s
DC vs.
node
cardioversion; ventric”,ar
other
~“nctons: tachywxdia; DPH.
stimulation
AVN. A-H
phenytain; cycle
AV
cuw.
node: plot
P. propranalol;
AVNCT. A-H
vs. PA,
AV atrial
node
conduction
sttm”Iation
procame
amide;
cycle PES.
length.
drugs.
with a retrogradely conducting bypass tract. (C) Atypical, often incessant, AV nodal reentry often features retrograde P waves with long R-P intervals. (D) The ratio of atrioventricular complexes: AV nodal reentrant tachycardias need not involve the atrium or ventricle, so that a 1:l relationship need not exist. Sinus or intraatria1 tachycardias may be accompanied by AV block. PSVT involving Kent bundle type of bypass tracts in the circuit always have a 1:l AV Kent bundle is ratio. (E) An ipsilateral suggested if the rate of a tachycardia slows during the presence of bundle branch block. Bundle branch block is more common in tachycardias involving a Kent bundle than in AV nodal tachycardias. (5) Physiologic maneuvers including carotid sinus massage, exercise, or physical tilting of the patient may result in autonomic and blood pressure changes that can affect a tachycardia. (6) Pharmacologic interventions using medi-
ELECTROPHYSIOLOGIC
51
TESTING
Table
Junctional
6.
(Continued)
AVN
Tachycxdias Concealed
ACAVNT
AN.NHT var
P-P.
WPW
HST
Enhanced
BYpaSS
WPW
AVN
IJames)
Maham
P
nnwtted
Normal
CT wide
in
II.III,AVF Parox
M non-
parox
t Slow
if 1p511
NO
Yes
NO
Yes
7 Yes
None
Slows
Yes Yes
if tpsdat.
s,ows
to Kent Significant
Vawable
Normal
a break
with
Norma,
or break
area
dseWhe(B AV
a Rat
Flat.
Flat
* Flat
Nwmal
+
+
C”,W
Namal
HBE
Variable Flat
delta
hrrt
or
rings
IAV
first
Kent
Antidramic:
near
HEE
Namaljshmt
Short
Namallshart
Normal
occ.
break
flat)
Olthadramic:
*bang
if ips,,.
to Kent
near
+
Fwst
near
HSE
Fmt
nex ““less
Inor
HBE Kent
Nwmal
Nwmal
NCW”A
Normal
Shortlnarmal
NO
No (unless
Shortlnwmal
medromicl NO
NO
Yes
Kent
NO
normal
Short
present) + Normal
+ Normal
Short.
P-R.
nwma,
ORS
Short
P-R,
ClftS May
be due
digitalis
to fox
D may rate
cause wth
rap,*
common
““common
A-F
VI
associated
really conc*aied 7P.D.”
PDPH
NO
Often
tIPA,
+ D.P
(AVNI
children
NO
cations that are fairly specific for affecting conduction and rhythmicity in individual portions of the heart may help in the diagnosis of some tachycardias. Sinus Node Tachycardia
A5 fa
(Figs. 11 and 12)
Sinus node reentrant tachycardia (SNRT)269-27’ is usually paroxysmal and often unsustained. The rate is moderate, typically below 150 and at times below 100 bpm. The mechanism of this tachycardia is assumed to be reentry within the perisinus nodal tissues. The conftguration of the high right atria1 depolarization may be different during tachycardia than during sinus rhythm, and following the termination of the arrhythmia, the configuration may not return immediately to its baseline state, perhaps because of refractoriness of those perinodal fibers involving the tachycardia. Chronic nonparoxysmal (automatic) sinus node tachycardia (CNPSNT) (Figs. 11 and 12) occurs due to increased automaticity of the sinus node in the absence of underlying diseases such
WPW
t PA.0
= normal
P-R:
Comma”
Speculation
D.P.V
PA.a
d&a only
SVT:
AVNRT
a WPW
N”
as thyrotoxicosis.*‘* The rate may range up to 200 bpm, but averages about 130. There are two variants: one group is propranolol responsive, suggesting that the mechanism may be inappropriate sympathetic tone. There is no association with the more generalized autonomic nervous system dysfunction syndromes.
Reentrant Atria1 Tachycardia (Figs. I1 and 12)
(PAT)27Q~27’~273-275
Reentrant atria1 tachycardia (“true paroxysmal atria1 tachycardia” or PAT) usually occurs in the setting of clinical heart disease. The rate and ECG appearance are variable. This rhythm may be either macro- or micro-reentrant. It may arise at any point in either atrium, perhaps involving specialized tracts in some instances.275 The atria1 waves may assume virtually any configuration on the ECG. “Pace mapping” from 12 atria1 sites in 69 patients resulted in diagnostically useful patterns only with left atria1 pacing near the left pulmonary veins (neg-
52
JOHN
JORMAL SANT AT
D. FISHER
IUAL AVN PATHS
A-H /
t
H-V s
QRS t
RAT7 WPW
I1&L
Fig. 12. Differential diagnosis of supraventricular tachycardia. Characteristic changes in the A-H, H-V, and QRS intervals are graphed on the ordinate as a function of increasing heart rate. which is displayed on the abscissa. SANT, sinoatrial nodal tachycardia. AT, intraatrial tachycardia. LGL. Lown-GanongLevine syndrome. WPW. Wolff-Parkinson-White syndrome.
A-H f H-V g
QRS t
RATF
ative P in lead 1) or inferior veins and coronary sinus (positive bifid P in V1).276 Automatic Atrial Tachycardia (Figs. 11 and 12)
fAAT}27’*278
The electrocardiographic presentation and the endocardial depolarization sequence of AAT are similar to those of reentrant atria1 tachycardia. Many patients with this arrhythmia have underlying heart disease, and it may be proportionately more common among children than among adults. The arrhythmia may be paroxysmal, but “permanent” atria1 tachycardia also occurs. The differential from other tachycardias is similar to that for reentrant atria1 tachycardias except that induction by programmed stimulation is rare. Atria1 tachycardia may occur as an escape mechanism after a sinus pause. In such cases, tachycardia following programmed atria1 extrastimuli (A2) does not occur immedi-
ately but only following a long equivalent to the sinus pause. affects the tachycardia but may treatment of heart failure tachycardia. Vagally Mediated Atria1 FIutter279
A2A3 interval Digoxin rarely be needed for in persistent
Atria1 Fibrillation
and
Vagal stimulation can convert atria1 flutter into fibrillation probably because of a shortening of the atria1 refractory period. Patients with the syndrome of vagally induced atria1 arrhythmias usually have hearts that are otherwise normal. Attacks of fibrillation or flutter are characteristically paroxysmal, and the essential feature is their occurrence at night or at rest rather than during daytime or exercise or emotional stress. Most episodes are preceded by progressive slowing of the heart rate, followed by relatively late premature beats (coupling interval greater than
ELECTROPHYSlOLOGlC
53
TESTING
350 msec), and ultimately by atria1 fibrillation or flutter. The most effective therapy has been directed at increasing the heart rate or prolonging the refractory period. Atropine, disopyramide in large doses, and particularly amiodarone are effective in this condition. Verapamil is generally of little use and digitalis and propranolol may worsen the condition. The most effective long-term therapy appears to be atria1 pacing at rates of 80 or more. Vagally mediated atria1 fibrillation or flutter should be considered in patients whose rhythms are said to be “drug resistant.” Atria1 Flutter2” Atria1 flutter is a regular intraatrial tachycardia with a rate usually in excess of 240 bpm. There is evidence to support both reentry and automaticity as the cause of flutter; but their role is unclear in the two types of atria1 flutter observed in both animal and human studies. Type 1 flutter is the classic type with “sawtooth” atria1 waves visible on the ECG, especially in the inferior leads and VI where the deflection is more negative than positive. The atria1 rate ranges from 240 to 340 bpm. Animal studies suggest an origin in the right atrium between the superior and inferior vena cava with a complex reentrant pathway responsible for the sawtooth configuration of the flutter waves. Type I flutter is subject to an “entrainment” phenomenon,2s’ which serves as a guide to the minimum rate of pacing required for termination with the least likelihood of induction of atria1 fibrillation, Allowing for changes in configuration due to the pacing stimulus, the flutter pattern initially is unchanged in its ECG morphology as the pacing rate increases, i.e., the arrhythmia appears to be pulled along or “entrained” by pacing. At a critical rate, the atrial complex will change in shape, and if pacing is stopped at this point, reversion to normal sinus rhythm usually occurs (see article by Waldo et al. also in this Symposium). Type II flutter is more rapid than type 1, ranging from 340 to 430 bpm, and on the surface leads often is represented by small positive deflections in the inferior leads and VI. Animal studies suggest that the apparent isoelectric baseline is not due to the absence of atria1
activity, but to the presence of concurrent opposing wavefronts. Earliest activation appears to be in the right atria1 margin at the junction between the right atria1 appendage and body of the right atrium. In contrast to type I flutter, type II virtually is impossible to terminate using pacing techniques, and treatment must be empirical. In some patients type II flutter may be difficult to distinguish from type I atria1 fibrillation. A V Nodal Reentrant Tachycardia (A VNR T)282-29’(Figs. 1 I and 12) AV nodal reentrant tachycardia may occur in paroxysmal or “permanent” forms. The mechanism ultimately is related to the presence of two or more pathways in the AV node that permit the establishment of a reentrant circuit. Usually the antegrade pathway during a paroxysmal tachycardia has a slower conduction velocity than the retrograde pathway (slow-fast form), but a fast-slow form also occurs. Clinically, patients afflicted with AV nodal reentry tachycardia may or may not have otherwise healthy hearts. The tachycardia rate is typically between 150 and 200 bpm but may occasionally be slower or faster. There are no typical changes in the QRS complex during normal sinus rhythm, and the P-R interval is of normal duration. During tachycardia there are no additional changes in the QRS complex unless there is a rate-related aberrancy. On the ECG, atria1 depolarization is commonly obscured when it is simultaneous with ventricular depolarization. The V-A (R-P) interval tends to be less than half the R-R interval in those cases where atria1 depolarization is visible; longer R-P intervals in AV nodal tachycardias are associated with atypical and resistant variants.268 A retrograde P prior to the QRS may be seen with the “fast-slow” variant. Electrophysiologic studies. The hallmark of AV nodal reentrant tachycardia is the identification of two or more AV nodal pathways and the induction of a tachycardia that can be shown to depend on these pathways. Dual A V node pathways. Incremental atria1 pacing normally results in a gradual increase in the A-H interval with increasing heart rates until the refractory period of the A-V node is reached. In patients with the common form of dual A-V nodal pathway, there is a break in the
54
curve such that at a given pacing rate the A-H interval will suddenly shift from a lower to a higher value. Dual pathways cannot always be identified during atria1 pacing or PES, either because of unidirectional conduction properties or because the faster pathway may have a shorter refractory period during antegrade conduction than the slow pathway.287-28g Ventricular of His bundle pacing or PES may reveal a break in the curve of the V (or H) to A interval with shorter cycle lengths. Alterations in refractoriness by agents such as atropinezs5 or procainamide286 may be required to achieve the balance of conduction velocities and refractory periods necessary to reveal the presence of dual pathways or to induce a tachycardia. Dual AV node pathways sometimes are identified in patients without a clinical history of paroxysmal supraventricular tachycardia, especially children.283 Determinants of AV nodal reentry. A low risk for development of paroxysmal tachycardia is suggested by absence of a history of tachycardia, absence of echo beats in response to atria1 premature stimulation, and lack of VA conduction during ventricular pacing.*‘* Neither the atrium nor the ventricle are vital to this tachycardia because the circuit is entirely within the AV node.284 Hence, AV nodal reentrant tachycardia may exist without regard to AV ratio. If there is biock in retrograde conduction from the AV node to the atrium, a situation may exist in which a supraventricular tachycardia (AV nodal) is present even though the ventricular rate is faster than the atria1 rate.284 Incessant or permanent form of A V nodal In addition to the reentrant tachycardia.28g-2g’ more common paroxysmal form of AV nodal reentrant tachycardia, there is another, more incessant, variety that is relatively more frequent in children. In contrast to the paroxysmal variant, antegrade conduction is usually by the faster pathway and retrograde conduction by the slower (fast-slow form). On the peripheral cardiogram, the onset of a tachycardia is heralded by an inverted P wave, which appears to conduct with a shorter P-R interval than did the sinus rhythm. During tachycardia, retrograde P waves precede the QRS. Although the fast-slow form can occur with paroxysmal AV nodal tachycardia, the slow-fast variety is more common, and results in a P wave that is either simultaneous with the QRS or follows it. The
JOHN
D. FISHER
“incessant” form actually is easy to stop temporarily with pacing techniques, and may even stop spontaneously, only to restart within a few beats. In paroxysmal AV nodal tachycardias, an atria1 premature beat results not only in block in the faster pathway, but in additional slowing of conduction in the slower pathway. With the permanent type of tachycardia, a premature beat is not required. The slow pathway is already sufficiently slow to allow reentry provided that unidirectional block occurs. Drug therapy often is unrewarding in patients with the incessant form of tachycardia, and pacemaker therapy, when successful, often involves the use of nonstandard sophisticated devices.2g’ Diferential diagnosis (Fig. 13). AV nodal reentrant tachycardia must be differentiated from other forms of PSVT. Sinus node and intraatrial tachycardias, and those due to lateral anomalous atrioventricular connections (Kent bundles), can be eliminated on the basis of depolarization sequence. Responses to measures that affect the AV node rather than the HisPurkinje system (e.g., carotid sinus massage, digitalis) help differentiate such a tachycardia from a His bundle tachycardia with retrograde block. The possibility of a retrogradely conducting concealed Kent bundle entering the atrium very near the AV node also must be considered. During ventricular pacing, such a septal Kent bundle conducts to the atrium with little increase in the V-A interval with increasing pacing rates, in contrast to the prolongation to be expected if conduction is via the AV node. Enhanced AV
ON 1258 Fig. 13. Anomalous AV connections. K. Kent bundle; J. James fibers: atrio-Hisian; atriofascicular; Erechenmacher fibers; M, Mahaim fibers: nodoventricular: fasciculoventriculer: AVN, AV node; BH, bundle of His. (See text.) Reproduced from Narula= by permission of the author and the American Heart Association.
ELECTROPHYSIOLOGIC
55
TESTING
nodal conduction may exist and mimicks the effects of a septal Kent bundle. Enhanced AV nodes, however, still respond typically to vagal maneuvers, parasympathetic drugs, and beta blockers, causing a prolongation in conduction not to be expected with an anomalous pathway. A ventricular extrastimuli, given just after the inscription of the His bundle deflection (i.e., when the His bundle is refractory), can be conducted back to the atrium only in the presence of an anomalous pathway. Demonstration of retroconduction during the refractory period of the His bundle may require the presence of a tachycardia. The retrograde equivalent to the Lown-Ganong-Levine syndrome in which an atrio-His bypass is presumed to exist would be suspected if V-A conduction were impossible during the refractory period of the His bundle, and if V-A conduction, when present, failed to respond to parasympathetic maneuvers. Nonreentrant Tachycardia Due to Simultaneous Conduction in Dual AV Node Pathways (AV Node Conduction Tachycardia. AVNCT)292 (Fig, 11) Rarely, conduction velocities will differ so markedly in the fast and slow pathways that impulses from each will be conducted to the ventricle. Thus, a single sinus beat results in two ventricular depolarizations. Depending on the relative conduction velocities, the peripheral ECG might reveal a regular SVT with the ventricular rate double that of the sinus rate or bigeminal rhythm, possibly with rate-related aberrancy of the second beat mimicking fixed coupled ventricular premature beats. In the patients studied, slow pathway conduction was permanent, and periodic block in the fast pathway resulted in varying degrees of block imitating a junctional rhythm with premature beats, or even atria1 fibrillation with a premature ventricular complexes. Arrhythmias due to this mechanism would depend on the absence of AV nodal echo beats. Automatic (Fig. 1)
Junctional
Tachycardia
(JT)293
These arrhythmias presumably arise in the AN and NH regions of the AV node and in the His bundle and may cause paroxysmal or nonparoxysmal junctional tachycardias (NPJT).
Atria1 pacing at rates faster than the tachycardia may result in 1:l conduction to the ventricles, but fails to suppress the ectopic focus. Atria1 and ventricular premature beats and pacing also are unable to initiate or terminate the tachycardia. Direct current cardioversion also fails, suggesting an automatic mechanism. In these patients, digoxin is useful for the treatment of congestive heart failure, but does not alter the tachycardia. Propranolol, reserpine, phenytoin, and chlorpromazine may be of some use. Quinidine and lidocaine appear to be ineffective. Digitalis toxicity may cause “PAT with block,” actually a form of atria1 or JT due to intraatrial or AN area reentry or automaticity. His Bundle Tachycardias
(HBT)2g3 (Fig. 1)
Tachycardias originating in the His bundle result in a narrow QRS complex unless raterelated aberrancy is present. Atrioventricular relationships will be determined by the retrograde conduction properties of the AV node. The H-V interval may be shorter than during sinus rhythm. Some of the automatic junctional tachycardias described above are His bundle tachycardias. Both reentry and automaticity can occur in the His Purkinje system and more will be said about such arrhythmias in the section on ventricular tachycardias. Tachycardias (AcAVNT)*~~
Related to Accessory (Fig. 11)
A V Nodes
Incremental pacing, antegrade or retrograde across the AV node, results in a steady increase in the A-H or H-A interval. Patients with dual or accessory A-V nodes, with slightly different conduction properties, act functionally as though they had two separate A-V node pathways. Electrophysiologic studies in this condition reveal evidence of this separation (as occurs in the Wolff-Parkinson-White Syndrome) with both pathways having A-V node-like properties including prolongation of conduction time with incremental pacing, and responsiveness to vagal tone, digitalis or propranolol. Tachycardias Connections: (Figs. 11-14)
Due to Anomalous AV Preexcitation Syndromeszs5~zs”
Preexcitation exists when conduction between the atrium and the ventricle occurs earlier than
56
JOHN
expected, often by a route other than the normal atrioventricular conducting system of the AV, His bundle, and bundle branches. Preexcitation may occur in either the ventricle or the atrium and may be overt or concealed. Tachycardias in neonates may be enhanced by predominant cholinergic innervation and may subside after several months with changes in autonomic tone, and as the natural process of fibrosis in the maturing heart ablates the anomalous pathway.297 The Wolff-Parkinson-White syndrome in older children is similar to that found in adults. 298In some patients, the presence of anomalous AV connections is unmasked after damage to the normal conduction system, e.g., following acute myocardial infarction.299 Wolff-ParkinsonSyndrome)
White Syndrome
(WP W
The hallmark of this most classic of preexcitation syndromes is the presence, during normal sinus rhythm, of a “delta” wave on the peripheral electrocardiogram. The delta wave occurs at the beginning of the QRS complex after an unexpectedly short P-R interval and represents preexcitation of the ventricle by anomalous conduction over a Kent bundle. The QRS complex is a fusion of ventricular depolarization caused by a Kent bundle that lies entirely outside of the normal atrioventricular conduction system and of depolarization following conduction through the normal system. The Kent bundle does not have the delaying properties of the normal AV node, accounting for the preexcitation of the ventricle. Amplitude and axis of the delta wave depend on the location of the Kent bundle, the relative time of arrival of a sinus impulse at the AV node and the anomalous pathway; the actual conduction velocity through the Kent bundle; and the degree of delay encountered by the wavefront in passing to the normal atrioventricular conduction system. The delta wave may be absent if the AV node conducts rapidly and the anomalous pathway is far lateral on the left (Fig. 14). Classification of Wolff-ParkinsonWhite synIt was previously customary to divide dromes. Wolff-Parkinson-White syndrome into type A and type B. Type A is characterized by an upright delta wave in lead VI often resulting in a right bundle branch block like configuration, and generally represents a left-sided bypass
D. FISHER
tract. Type B is characterized by negative delta wave in V 1, mimicking an anterior wall myocardial infarction or a left bundle branch block and generally occurs with right-sided Kent bundles. Detailed mapping studies have shown that Kent bundles may exist almost anywhere around the atrioventricular valve rings, and a more complicated classification system has proved necessary. Kent bundles are now described as right or left posterior, lateral, or anterior, and right or left anterior or posterior paraseptal. WP W-related tachycardias. This syndrome is the archetype of the macroreentry tachycardia. During tachycardia, antegrade conduction is usually via the normal atrioventricular conduction system (orthodromic) with retrograde conduction through the Kent bundle resulting in a tachycardia with a narrow QRS complex. This often is termed a supraventricular tachycardia but the mechanism is actually an atrioventricular macroreentry circuit. Since conduction proceeds from ventricle to atrium, the atria1 depolarization follows the QRS complex rather than being concurrent as occurs with some AV nodal tachycardias. The presence of an inverted P wave in lead I during tachycardia strongly suggests the presence of a left-sided Kent bundle, but intraatrial tachycardia originating in the left atrium will occasionally be encountered. Less commonly, antegrade conduction occurs over the Kent bundle (antidromic conduction), creating a wide QRS simulating ventricular tachycardia; retrograde conduction then occurs via the normal pathway. Intermittent bundle branch block. Aberrant conduction due to a rate-related bundle branch block may occur and can provide diagnostic challenges as well as insights. As with aberrantly conducted supraventricular tachycardia, the rhythm must be distinguished from ventricular tachycardia. Of diagnostic interest, bundle branch block occurring on the same side as a Kent bundle will result in a lengthening of the cycle length of the tachycardia (a slowing of the rate) because the ventricular portion of the circuit will take longer to complete in the presence of ipsilateral bundle branch block. Antegrade (antidromic) conduction through a Kent bundle occurs less commonly than retrograde, but if present, again must be distinguished from ventricular tachycardia. With antegrade conduction through the Kent bundle,
ELECTROPHYSIOLOGIC
57
TESTING
l
0 khoii
Trad
Conduction
E
Bundle NSR
Jomos NSR
of Kant
Conduction I
and
Kant
Fibror
C James NSR
Tract CowhAon I
F Jomor NSR
ond
Yahaim
Fibns
A
AP
*-+
w
l-2 J-6 Fig. 14. Effects of atrial pacing types and combinations of anomalous and the American Heart Association.
on conduction intervals and the AV connections. Modified from (See Figs. 10 and 12 and text.)
retrograde conduction is relatively slow as it occurs via the AV node, and the V-A interval is generally longer than encountered with retrograde conduction through the Kent. Enhanced AV node conduction commonly occurs in WPW patients, however, so that retrograde AV node conduction may be rapid. Electrophysiologic studies.296.3w306During sinus rhythm intraatrial conduction periods are normal as is the A-H interval in most patients. The H-V interval is abbreviated because of ventricular preexcitation. During incremental atria1 pacing, the A-H prolongs normally, unlessan enhanced AV node is present, but there is little change in the A-V interval becauseof rapid conduction through the Kent bundle. The His bundle potential gradually moves into the ventricular depolarization complex and may become invisible. If the refractory period of the Kent bundle is longer than that of the normal atrioventricular conduction system,
QRS complex and Narula.‘w
in normals reproduced
and in patients by permission
with various of the author
there will be an abrupt change to normal conduction when the pacing cycle length is shorter than the refractory period of the Kent bundle. Pacing at multiple atria1 sites until the preexcitation is maximized helps to localize the site of the anomalouspathway.304 Atria1 programmed stimulation, early enough to find the Kent bundle refractory to antegrade conduction, still may be conducted rapidly enough through the normal system so that the impulse arrives at the Kent bundle from the ventricular direction before the end of its refractory period. Somewhat earlier premature beats may encounter sufficient delay in the AV node sothat the impulse arrives at the ventricular side of the Kent bundle after the end of its refractory period. Conduction proceeds to the atrium where, if the AV node no longer is refractory, antegrade conduction will occur and the tachycardia is established (Fig. 15). Retrograde conduction in the WPW syn-
58
JOHN
A NSR
C h&mediate
RLateAPC
D. Early APC
APC
Fig. 15. Initiation of tachycardia in patients with WPW syndrome: diagrammatic scenerio. RA, Right atrium: AVN. AV node: RV, right ventricle; LA, left atrium: LV, left ventricle; APC. atrial premature complex. (A) During normal sinus rhythm, conduction proceeds to the AV node and through the Kent bundle, which causes a delta wave. (BI A late APC is blocked in the Kent bundle, but proceeds to the AV node rapidly enough so that the Kent bundle is still in its refractory period. preventing retrograde conduction to the atrium. (Cl A critically timed premature beat is blocked in the Kent bundle and encounters sufficient delay in the AV node so that it is no longer refractory to retrograde conduction and a macroreentrant tachycardia is initiated. (Dl An earlier APC results in block at both the AV node and the Kent bundle.
drome.307-3’0 Ventricular stimulation during sinus rhythm results in ventricular to atria1 conduction with little change in the V-A interval. V-A conduction of an extrastimulus delivered during the refractory period of the His bundle further confirms the presence of an anomalous pathway. This is demonstrated more easily during tachycardia. Electrode positions and endocardial mapping. Strategically placed recording electrodes are able to determine the earliest point of depolarization due to conduction through the Kent bundle. Electrodes are placed in the high right atrium, right ventricle, and His bundle positions. During orthodromic (“SVT”) tachycardia or ventricular stimulation, a mobile lead is maneuvered around the right atrium with particular attention to the tricuspid ring and the time of atria1 depolarization at each point compared with that recorded at the His bundle position. A modification of the Brockenbrough needle, ordinarily used for transeptal catheterization, has proved useful for mapping the tricuspid annu1~s.~‘~Left-sided pathways generally are studied using recording electrodes in the coronary sinus, which runs in the AV groove between the left atrium and ventricle. Observations during tachycardia. The depo-
D. FISHER
larization sequencecan be mapped during tachycardia as described above. Evidence of more than one pathway may be found. During tachycardia with retrograde conduction via the Kent bundle, atria1 stimulation can terminate the tachycardia in several ways: (1) The Kent bundle can be depolarized in an antegrade fashion rendering it refractory when approached by the retrograde impulse. This is most effective when the stimulating electrode is near the Kent bundle. (2) Atria1 stimulation can cause the atrium or the AV node to be refractory to the reentrant wavefront after it passesthrough the Kent bundle. (3) The premature beat may be conducted initially through the atrioventricular conduction system and reach the Kent bundle when it still is refractory to retrograde conduction Similarly, ventricular stimulation can terminate reentrant tachycardia associated with the WPW syndrome by causing refractoriness in the normal atrioventricular conduction system, the ventricle, the Kent bundle, or after retrograde conduction through the Kent bundle by its effects in the atrium. Concurrent .SV7’.3”-313 Patients with the WPW syndrome are not immune to tachycardias due to other mechanisms. AV nodal reentry tachycardias have been identified in such patients and may in fact be the mechanism for tachycardia in some. Automaticity in the anomalous bundle.3’4*3’s Escape beats arising from the anomalous bundle have been documented in patients with WPW syndrome.314Postmortem studies on one patient revealed that the anomalous pathway occurred in a fault in the mitral annulus through which there was a direct AV connection containing P cells resembling those found in the patient’s own sinus node.3’5 Atria1 fibrillation and the WPW syndrome.3’“32’ Atria1 fibrillation conducted rapidly down the Kent bundle can result in extremely rapid ventricular rates, ultimately degenerating into ventricular fibrillation. Digitalis may lengthen or shorten the refractory period of the Kent bundle, slowing or increasing the ventricular rate during atria1 fibrillation. Other drugs, including lidocaine, also have unpredictable effects on Kent bundle conduction. Assessment of the maximum rate of AV conduction across a Kent bundle can be performed in two ways. First, the atrium can be
ELECTROPHYSIOLOGIC
59
TESTING
fibrillated by rapid atria1 pacing or extrastimuli and the shortest R-R interval observed is taken as maximum possible rate. Rapid atria1 pacing provides another, perhaps less accurate, assessment of the maximum possible rate. During atria1 fibrillation, the mean shortest R-R of patients developing ventricular fibrillation was 180 msec, versus 240 in nonfibrillators.320 The weak link hypothesis. In macroreentry tachycardia, such as that associated with WPW syndrome, the impulse travels through a wide variety of tissues, each with its own conduction velocity and refractory period. Susceptibility to block at each of these sites will vary markedly among individuals. In some, the tachycardia can be terminated by block at the AV node using medications such as verapamil, digitalis, and propranolol. In others, the site of the weak link is at the Kent bundle itself, which is most susceptible to the actions of quinidine, procainamide, and disopyramide. Some of the newer antiarrhythmic agents, such as aprindine and amiodarone, also have proved markedly effective in patients with the Wolff-Parkinson-White syndrome. The position of the weak link also dictates the physiologic maneuvers that are most likely to be usefu1.322 In patients with the weak link at the AV node, termination will be enhanced by a supine posture with the legs elevated and by vagal maneuvers such as carotid sinus massage. When termination of the usual form of WPW tachycardia occurs after the ventricular impulse, the accessory pathway is indicated as the weak link. In these patients, termination will be favored by increasing bombardment of the accessory pathway by favoring AV nodal conduction. Therefore, such patients should assume an upright posture with legs dependent, and vagal maneuvers should not be used. Mahaim Fibers: The Pseudo- WP W Syndrome296*306 (Figs. I I, 13, and 14) Mahaim fibers are composed of Purkinje-like fibers that arise prematurely from the AV node (nodoventricular fibers), His bundle, or bundle branches (fasciculoventricular fibers), resulting in a delta wave on the electrocardiogram. Because all impulses traverse the AV node there is some delay and the P-R interval is rarely shorter than 0.12 sec. With incremental atria1
pacing, the A-H interval prolongs and there is no increase in aberrancy such as is seen in the presence of Kent bundles and the WPW syndrome. His bundle pacing normalizes the QRS with nodoventricular fibers (pacing site is distal to the anomalous fibers), but delta waves remain if fasciculoventricular fibers are operative. Discussions of tachycardias related to Mahaim fibers are largely conjectural. The Lown-Ganong-Levine (Figs. 1 I, 12, and 14)
Syndrome296,323-32b
The Lown-Gangong-Levine Syndrome consists of the electrocardiographic pattern of a short P-R interval and a normal QRS complex both during sinus rhythm and (usually) during tachycardia. There are several mechanisms for this pattern. AV nodal bypass tracts (atrio-His tracts).‘23 AV nodal bypass tracts often are referred to as James or Brechenmacher fibers and are conceptualized as strands of the intraatria1 internodal pathways that “miss” the AV node and insert below it in the His bundle. Such pathways are rare.323 With atria1 pacing, the A-H interval remains virtually constant until the refractory period of the pathway is reached. If conduction through the AV node is still possible, the A-H interval jumps to a level appropriate for AV nodal conduction at that rate, mimicking the pattern seen in dual AV nodal pathways except for the flatness of the initial portion of the curve. AV nodal bypass tissues may be affected little by vagal maneuvers. Enhanced AV node conduction.306*324 Enhanced AV node conduction has been defined as an abnormality of AV conduction consisting of (1) A-I-I interval in sinus rhythm 60 msec or less; (2) 1:l AV conduction maintained during atria1 pacing to rates of 200 bpm or more; (3) maximum A-H interval prolongation of 100 msec or less. The AV node remains susceptible to vagal maneuvers and beta blockade. Short P-R interval without enhanced A-V node conduction. In spite of a short A-H and P-R interval during sinus rhythm, the other criteria for enhanced AV node conduction are not met. Typical dual AV node pathways may be identified in some such patients, with the faster pathway having a relatively long refractory period. Normal P-R or A-H longer than 60 msec but
60
other evidence of enhanced AV node conduction or bypass: flat A-H curve, with other criteria of enhanced AV node conclusion (see above); “concealed LGL.” Mechanisms of tachycardia in the LGL syndrome.‘24q325 True AV nodal bypass tracts are rare and probably account for very few instances of tachycardia. AV nodal reentrant tachycardia is the most common mechanism encountered in patients with the LGL syndrome, followed by tachycardias due to concealed Kent bundles, which will be discussed in the next section. Patients with the LGL syndrome may have tachycardia due to other causes, with the short P-R interval acting as an innocent bystander. A high incidence of ventricular arrhythmias, including tachycardia and fibrillation, has been observed in patients with the LGL syndrome.324q326The potential for rapid AV conduction in patients with enhanced AV nodes may increase the risk of ventricular vulnerability in a manner analogous to those with WPW syndrome and rapid conduction of atria1 fibrillation. Tachycardias Related to Concealed Kent Bundles327-333 Some Kent bundles conduct only retrogradely from ventricle to atrium, and therefore are associated with atria1 but not ventricular preexcitation. During sinus rhythm there is nothing on the ECG to reveal the presence of a functioning Kent bundle. Tachycardias due to concealed anomalous (retrograde) conduction account for a large share of supraventricular tachycardias, probably second only to AV nodal reentry. Atria1 fibrillation does not appear to pose an inordinate threat to these patients, as accelerated antegrade conduction down extranodal bypass tracts is not a feature of this condition. Although right-sided bypasses have been described”’ the majority of these tracts appear to be on the left. A “supraventricular tachycardia” with inverted atria1 depolarizations in lead I, in a patient without a history of delta waves during sinus rhythm, usually is due to a left-sided retrograde “concealed Kent bundle.” Electrophysiologic features. During incremental pacing, all intervals behave normally. Incremental ventricular pacing results in retrograde conduction with little or no prolongation of
JOHN
D. FISHER
the V-A interval and a retrograde sequence of depolarization that depends on the location of the bypass tract. Difirential diagnosis. Tachycardias due to concealed retrograde conducting Kent bundles can be differentiated from tachycardias originating in the atrium by observing the sequence of atria1 depolarization during tachycardia or ventricular stimulation. Absence of evidence of dual AV node pathways usually will differentiate these arrhythmias from those due to AV nodal reentry. The possibility of a septal retrograde Kent bundle also must be distinguished from a tachycardia due to James fibers. Variations of the Lown-Ganong-Levine syndrome usually are revealed during sinus rhythm by the short P-R interval and during incremental atria1 pacing by failure of the A-H interval to prolong normally. The differential between a concealed retrograde conducting James fiber and a septal retrograde Kent bundle can be made by taking advantage of the relatively long refractory period of the His-Purkinje system: a ventricular premature beat delivered just after the inscription of the His bundle depolarization would occur at the time when the His bundle is refractory. Therefore, any conduction back to the atrium would have to occur over a pathway that did not include the His-Purkinje system, i.e., over a septal Kent bundle rather than via an atrio-His (James) tract. Bundle branch aberrancy occurs more often in tachycardia involving a Kent bundle than in those related to AV node reentry.33’“32 AV node reentry tachycardias typically are initiated by an atria1 premature beat that conducts antegradely over the slow pathway, giving the His-Purkinje system adequate time for repolarization. In tachycardias involving Kent bundles, antegrade conduction over the AV node is less delayed, and the His-Purkinje system may not be fully repolarized, giving rise to bundle branch aberrancy. Aberrant QRS complex may also be caused by concealed retrograde invasion of the bundle branches.333 Concealed (Retrograde Conducting) Ganong-Levine Equivalent334
Lown-
Ventricular stimulation also can result in atria1 preexcitation in a pattern suggesting partial AV node bypass or enhanced AV node
ELECTROPHYSIOLOGIC
61
TESTING
conduction, or retrograde conducting “James” fibers. The differential diagnosis is outlined above. Concealed (Retrograde Fibers
Conducting)
Mahaim
Retrograde conducting Mahaim fibers, not yet confirmed, but included here for the sake of symmetry, would not be revealed by a delta wave during normal sinus rhythm. Tachycardia might involve a reentrant circuit of Mahaim to ventricle to bundle branches to Mahaim or vice versa. During tachycardia, a bundle branch block pattern would emerge if the Mahaim fibers arose in the bundle branches or if antegrade conduction was via the Mahaim fibers. A normal QRS configuration would persist if the abnormal fibers arose from the His bundle or AV node or whenever antegrade conduction utilized the normal pathways. Diagnostically, evidence of dual AV node pathways or atrioventricular bypass tracts in conjunction with a normal retrograde sequence of atria1 depolarization must be excluded. Premature beats in the atrium would not disturb the timing of this rhythm. Tachycardias associated with Mahaim fibers would include the ventricle in the circuit and ventricular depolarizations would be expected to affect the timing of the tachycardia. Concealed (Retrograde A v Node294.33S.336
Conducting)
Accessory
Accessory pathways with conduction properties typical of AV nodal tissue usually are septal in location. Variants capable only of retrograde conduction predominate. Both paroxysmal and incessant forms of tachycardia occur in patients with accessory AV nodal-like tissues. During ventricular pacing or programmed stimulation, two different atria1 sequences of retrograde activation occur, a phenomenon not yet described with a single AV node.ls2 In some patients,336 the pathway is concealed only because its conduction is slower than that of the normal pathway. A tachycardia equivalent to an antidromic mechanism seen in the WPW syndrome has been observed in one such patient316 Anterograde conduction occurred through the anomalous pathway with a QRS configuration suggestive of right ventricular apical activation and masquerading, therefore, as a ventricular tachycardia.
This tachycardia could be induced by an atria1 premature beat that blocked in the AV node (A-H block) with subsequent conduction down the accessory pathway to the right ventricular apex after a prolonged P-R interval of 300 msec. In contrast to most fibers of the James or Kent type, conduction in accessory AV nodes typically is enhanced by atropine and would be expected to be depressed by vagotonic maneuvers and beta blocking agents. The Role of Electrophysiologic Studies in the Operative Management of Supraventricular and Anomalous Pathway Tachycardias
Indications for Surgery329~337~340 Surgery may be useful in patients with lifethreatening tachycardias unresponsive to medical or pacing therapy. Patients with very rapid paroxysmal tachycardias, utilizing an anomalous antegrade conduction pathway, form the most dramatic group of candidates for surgery. Patients debilitated by the incessant forms of tachycardia may also derive relief from surgery. 329,339 There still is someconcern over the definition of refractoriness to medical and pacer therapy.338In the case of the WPW syndrome, Kent bundles with refractory periods of 270 msecor lesstend to resist pharmacologic modification.340Surgery offers the only definitive cure and might be sought by younger patients who would otherwise have to look forward to a lifetime of medical therapy. Importance of the preoperative study. The advantages of minimizing the number of surprisesand therapeutic decisionsin the operating room are obvious. The effects of anesthesia or inadvertent trauma due to manipulation of the heart during surgery can have important effects on electrophysiology and may prevent the initiation of a tachycardia or temporarily suppress conduction in a bypass tract. In such cases, precise location of the bypass tract during a preoperative study can result in successful “blind” ablation at surgery.34’ Epicardial and endocardial mapping in supraventricular and preexkitation tachycardias263.337m339,34’-345 (Fig. 16). Atria1 endocardial and epicardial mapping have been used to localize intraatrial SVT342 and to identify the AV
62
JOHN
D. FISHER
increased by atria1 pacing at a relatively rapid rate near the site of the bypass, as determined from the preoperative study. Ventricular pacing in patients with WPW syndrome and retrograde conduction over the anomalous pathway results in preexcitation of the atrium at the point of the bypass. In patients whose bypass tract is located in the septum, epicardial breakthrough during atria1 pacing will occur after the onset of the delta wave on the electrocardiogram, and endocardial mapping techniques must be used to complete localization of the bypass. Following attempted surgical correction of the tachycardia, efforts should be made, while in the operating room to confirm the success of the procedure. In patients with WPW syndrome, evidence also should be sought for the existence of additional pathways whose presence may have been masked by more rapid conduction through the previously identified, now ablated, pathway.
HP?4
ANTERIMI
LEFT LATEIL
VENTRICULAR TIfllNG REFERENCE: MA-PI ATRML TIMING REFERENCE: LV-PI ~1
628AC Epicardial mapping the WPW syndrome. The Fig. 16. epicardial surface of the heart is divided into a grid based on that used by Gallagher et al. During pacing of the left atrial appendage, earliest ventricular activation occurs at the base of the left ventricle at the acute margin 110 set after the pacer impulse (PI). Depolarization then proceeds radially. During left ventricular pacing at the point marked by the circled asterisk, the earliest atrial activation is at a point adjacent point. which is activated first during atrial pacing.
node and His bundle for ablation in patients with incessant supraventricular tachycardias.338.339*343 Epicardial mapping has been particularly useful in patients with the WPW syndrome.34’“” The normal sequence of epicardial activation345 begins on the anterior surface of the right ventricle near the left anterior descending artery, remote from the AV ring. In contrast, the earliest epicardia4 activation in patients with Wolff-Parkinson-White syndrome occurs near the AV rings (Fig. 16). Since conduction often occurs via the normal pathway in these patients, the degree of anomalous conduction can be
Surgical Techniques A detailed discussion of surgical techniques is outside the scope of this review. Removal of an atria1 focus may be accomplished through an atriotomy, or amputation in the case of a focus localized to the appendage.342 His bundle ablation has been accomplished by incision, suturing, and injection of sclerosing substances. The large experience at Duke University has led to vast improvements in the surgical approach to WPW.346 Perhaps the most important point is that the Kent bundle may insert anywhere from immediately adjacent to the annulus to a point fairly far out on the ventricular surface (Fig. 17). The usual approach is to make an incision along the mitral annulus centered about the point of the bypass as determined from mapping. Then, working from the inside of the atrium and using blunt and sharp dissection through the incision at the annulus, the epicardial surfaces of the ventricle and often the atrium are denuded over a substantial area. Cryosurgical techniques also have been introduced for treatment of incessant supraventricular tachycardia339.343 and the WPW syndrome.347 Cryosurgery appears to have some advantages. Temporary block of conduction can be achieved by cooling to 0°C. Since recovery of conduction subsequently occurs, any “trial and error”
ELECTROPHYSIOLOGIC
63
TESTING
NERVE HOOK
Fig. 17. Surgical procedure for treatment of WPW. The left-hand panel represents a cross-section of the left side of the heart at the level of the AV groove. Possible Kent bundle locations are shown in black. Successful surgical ablation of the His bundle is accomplished working from inside the atrium through an incision at the ennulus. Epicardial structures are pushed back leaving a denuded left ventricular surface. Based on the experiences at Duke University.
needed to localize the abnormal area need not cause permanent damage to normal tissues. Permanent ablation of the abnormal areas is accomplished with freezing at -60°C for 2 or more 90-set applications. Other benefits of cryosurgery have been observed during acute and chronic animal studies.348When applied to the ventricle, ectopic activity can be localized to the edge of the cryolesion, but this disappearswithin a week, leaving an electrically silent area. Histologically, the chronic cryolesion is a well demarcated firm scar like an innert plug without disruption of surrounding tissues. Electrophysiologic testing for the control of SVT and preexcitation tachycardias will be discussed following the section on ventricular arrhythmias.
Ventricular
Tachycardias
(VT)
Ventricular tachycardias are diverse in origin, configuration, associated disease states, rate, and malignancy.349Many patients referred to the arrhythmia service at our hospital with recurrent ventricular tachycardia had been mistakingly diagnosed as having supraventricular tachycardia with aberrancy. These patients often are
subjected to the usual emergency room routine for the treatment of supraventricular tachycardia, thereby possibly prolonging the duration of the arrhythmia. The responsivenessof some ventricular tachycardias to vagal maneuvers350,35’ only serves to enhance the illusion. Ventricular tachycardia originates in the ventricle, is maintained independently of atria1 participation, and has a rate in excess of that appropriate for an idioventricular rhythm. There does not appear to be any virtue at present to defining VT as a rhythm with a rate in excessof 100 bpm. Although slower rates often are considered to be due to accelerated idioventricular rhythms, some tachycardias with rates well in excess of 100 bpm can be slowed to rates far below 100 bpm under the influence of antiarrhythmic drugs, without change in configurations or, presumaccelerated ably, mechanism. Additionally, idioventricular rhythms may exceed 100 bpm, again without apparent change in configuration or mechanism.
Electrocardiographic Features Classically, the diagnosisof ventricular tachycardia is made easier if conducted sinus beats or
64
JOHN
fusions with sinus beats can be observed during the tachycardia. Unfortunately, in the majority of patients, such conducted beats are not observed because of antegrade refractoriness in the conduction system or because there is sufficient retrograde conduction during ventricular tachycardia to overdrive the atria. Evidence of AV dissociation strongly favors the diagnosis of ventricular tachycardia; rhythms such as AV nodal reentrant tachycardia with retrograde block are much less common. Ventricular tachycardia must be distinguished from supraventricular tachycardia and guidelines have been proposed based on electrophysiologic studies that help make this distinction352 (Fig. 18). Seventy episodes of ventricular tachycardia and 70 episodes of aberrantly conducted supraventricular tachycardia were compared in patients whose baseline cardiograms did not have bundle branch or fascicular block. Findings suggesting a ventricular origin of the tachycardia were: (1) QRS duration greater than 0.14 set; (2) left axis deviation; (3) certain configurational characteristics of the QRS. For patients whose tachycardia had a right bundle branch block configuration during tachycardia, a pure R wave in V 1, an Rsr’, a QR or an RS configuration; in V6 an rS, an S, a QR, possibly a pure R wave. For patients whose tachycardia had a left bundle branch block configuration,
Vl SVT 43 VT 45
22 25
0 12
0 4
V6 SVT 48 VT 45
22 25
0 1
12 10
TOTALS SVT 48 VT 45
22 25
0 13
12 14
*LEFT
BRANCH
BUNDLE
CONFIGURATIONS
7
12 2
17 20
there were no distinguishing characteristics in V 1, but in V6, qR and Qrs complexes were found only in patients with ventricular tachycardia. (4) AV dissociation; (5) rates below 170 bpm for patients with right bundle branch block configuration. A definitive diagnosis is not always possible without invasive studies. Reliable guidelines for patients whose baseline electrocardiogram features partial or complete bundle branch block have not yet been established. During electrophysiologic studies, the diagnosis of ventricular tachycardia may be based on the following observations. (1) The presence of AV dissociation, especially if the block is at the H-V level. (2) Absent or randomly distributed His bundle potentials also are definitive if antidromic tachycardias related to the WPW syndrome have been ruled out. His bundle potentials in regular relationship to the ventricular depolarization can be observed, in somecasesof ventricular tachycardia, by mechanismsthat will be discussedbelow. In such cases,supraventricular tachycardias should be ruled out using criteria described in the sectionson supraventricular tachycardia. (3) The tachycardia should not meet any of the criteria outlined above for supraventricular or preexcitation tachycardias. (4) If a 1:l AV relationship exists, there are three possibilities: isorhythmic tachycardias may coexist; 1:1 V-A conduction may be present; or
28 2
4
10
0
11
9
+
0
12
15
2
0
10
13
31 2
0 6
12
23
2
2
15 14
2 18
31 2
1 18
NOT REPORTED
D. FISHER
SEPARATELY
FOR
l
25
0 1
0 11
22 25
0 1
0 11
---
l
VI
Fig. 18. Differential diagnosis of ventricular tachycardia and aberrantly conducted supraventricular tachycardia. EGG configurations in leads Vl and V6 were compared in 70 episodes each of supraventricular tachycardia with and ventricular tachycardia in patients without bundle block or hemiblock during normal sinus rhythm. Although considerable overlap in sotne patients, other patterns are reasonably specific. (After Wellens.‘“)
Typical aberrancy there is
ELECTROPHYSIOLOGIC
65
TESTING
the rhythm may be supraventricular in origin. Atrial and ventricular pacing and premature beats will establish quickly whether the rhythms are independent or related, as well as the direction of conduction. (5) The effects of atria1 pacing can be most enlightening. The diagnosis of VT is favored if atria1 pacing at or above the tachycardia rate restores in a normal QRS configuration, or if AV block occurs at rates far below that of the tachycardia. If, during VT, atria1 pacing is performed at rates faster than the tachycardia and results in an increase in the ventricular rate without change in the QRS complex, the finding may be nondiagnostic; although compatible with aberrantly conducted supraventricular tachycardia, this also may represent entrainment of a ventricular tachycardia, a phenomenon that will be described briefly in the section on pacing for tachycardias. Mechanisms
of Ventricular
Tachycardia
Ventricular tachycardia may be due to macroor microreentry, automaticity, and triggered automaticity. As discussed previously, the clinical differential is difficult to make with great confidence. Sequential changes following experimental myocardial &hernia or infarction.353”62. Immediately following experimental coronary occlusion there are abrupt changes favoring the development of reentry arrhythmias; commonly a relatively slow idioventricular rate punctuated by episodes of ventricular tachycardia and fibrillation persists for approximately 20 min following occlusion. The dispersion of refractoriness and conduction properties is enhanced by rapid rates whether due to pacing, sympathetic tone, or atropine, and these are accompanied by exacerbation of the arrhythmia. Vagal tone, or withdrawal of sympathetic tone, tends to decrease the electrophysiologic disparities and the incidence of arrhythmia. Reperfusion of an occluded area before irreversible damage has occurred results in a different type of malignant arrhythmia.357~358 The idioventricular rate between episodes of tachycardia or fibrillation is faster than during occlusion. The arrhythmias are unaffected by changes in autonomic tone, but may be suppressed by rapid pacing. These findings are consistent with an automatic mechanism, but
inhomogeneous improvement in conduction also may establish reentrant pathways. Twenty-four hours following this experimental coronary occlusion, initial electrical activity, during arrhythmias, appears to arise within the surviving subendocardial Purkinje cells.359m360 The arrhythmias have the characteristics of enhanced automaticity. Three to 9 days after experimental myocardial infarction, evidence of enhanced automaticity usually declines. Recordings from multiple sites in the infarcted area, using a composite electrode, documents the presence of continuous electrical activity with low amplitude potentials bridging the diastolic interval between beats, resulting in a reentrant type of arrhythmia.36’ In the chronic postinfarction period, from months to years following the initial event, subendocardial tissues, especially Purkinje fibers, remain histologically intact in spite of extensive scar formation in the area of the infarct.3s3’362 Reentry in the His-Purkinje system. Reentrant circuits involving the Purkinje system have been demonstrated in experimental preparations.7’“63 Reentry in the human His-Purkinje system has been documented364 during right ventricular apical programmed stimulation. A critically timed beat finds the right bundle branch refractory to retrograde conduction. Slow conduction to the left ventricle finds the left bundle receptive to retrograde conduction. The impulse travels retrogradely up the left bundle and His bundle and produces a reentrant ventricular systole by antegrade conduction down the right bundle branch. A recently described variant produces intraventricular reentry with a narrow QRS complex.365 The retrograde limb was one of the divisions of the left bundle branch and the antegrade limb was (simultaneous conduction) in the right bundle branch and the other division of the left bundle branch. Reentry tachycardias with the main bundle branches participating in the circuit (macroreentry) have been reported3’j6 but are felt presently to be uncommon. Microreentry. Most cases of ventricular tachycardia appear to be due to a microreentrant circuit localized within a limited area of the ventricle. Evidence for such microreentry circUits367,368 Include . the following: (1) lack of
66
JOHN
retrograde His-Purkinje conduction delay for initiation of tachycardia; (2) bundle branch reentry not required for initiation of tachycardia; (3) the presence of H-V block has no effect on the tachycardia; (4) random retrograde His bundle potentials observed during tachycardia; (5) large segments of both ventricles can be captured without affecting the tachycardia; (6) conducted supraventricular beats fail to affect the timing of the tachycardia; (7) areas of continuous local electrical activity, analogous to that observed in experimental infarctions, have been observed in patients with aneurysms.369 Tachycardias with different QRS configurations in the same patient may indicate the existence of more than one ectopic (microreentrant) circuit, or multiple points of exit or change in conduction within a single area.“‘.“’ Automaticity. The potential for automatic tachycardias was outlined above in the section on the course of arrhythmias following experimental myocardial infarction. The possibility of triggered automaticity in one patient has been raised.“’ In patients with known recurrent sustained tachycardia, the arrhythmia can be reproduced by programmed stimulation in most cases, suggesting further that reentry is the chief mechanism for ventricular tachycardia in man. Programmed stimulation would not be expected to initiate or terminate tachycardia due to enhanced automaticity. Arrhythmias due to triggered automaticity should be sensitive to verapamil, an agent, however, which clinically has been of indifferent effectiveness in ventricular tachycardia. Ventricular
Fibrillation
This most disastrous of ventricular arrhythmias may be defined as chaotic, random, asynchronous activity of the ventricles due to repetitive reentrant excitation and/or focal discharge.“’ Ventricular fibrillation is facilitated by inhomogeneity in conduction velocity and refractory periods and by a large ventricular mass. Ventricular fibrillation is difficult to achieve experimentally in small hearts or in small portions of large hearts, the critical mass in ventricular muscle requiring a surface area of at least 4 sq cm.“’ Microelectrode studies have not revealed characteristic abnormalities in the cells of a fibrillating preparation, but the rapid
D. FISHER
rate results in slowly rising action potentials and asynchronous depolarization of closely adjacent cells, tending to perpetuate the arrhythmia.373 When ventricular fibrillation occurs during eiectrophysiologic studies in humans, it usually is caused by two ventricular programmed extrastimuli in patients with documented or suspected ventricular tachycardia or fibrillation.374 Ventricular fibrillation occurring during electrophysiologic studies begins, in most patients, as a rapid and accelerating ventricular tachycardia with discrete local electrograms that ultimately become fragmented and disorganized. Experimentally, the ventricular fibrillation threshold (VFT) is measured by applying stimulation at increasing amplitudes until fibrillation occurs.375 The VFT in humans undergoing open heart surgery376”77 were less than 20 mA in patients with coronary disease and more than 20 mA in patients undergoing surgery for correction of congenital defects or valvular heart disease. Electrophysiologic Studies in Patients With Ventricular Tachycardia349~37s”91 Electrophysiologic studies are useful in establishing the most effective medical or pacing treatment for recurrent tachycardia or in laying the groundwork for surgery. As with other tachycardias, much can be learned by observations during (1) induction of tachycardia; (2) established tachycardia; (3) termination of tachycardia. Stimulation techniques. Programmed stimulation, burst, and ramp pacing have been described earlier and all are useful in the study of ventricular tachycardia. Atria1 stimulation. Atria1 programmed extrastimuli or incremental pacing may result in the induction of ventricular tachycardia.392 Ventricular stimulation. Incremental ventricular pacing occasionally results in the induction of tachycardia, but as a rule, does not offer important insight into the mechanism of VT. Programmed extrastimuli (PES), however, commonly result in the induction of ventricular tachycardia in patients with a history of such an arrhythmia. (details are provided below in the section on serial testing). In some patients, two tachycardia induction zones can be determined.“’ In patients with a wide tachycardia initiation zone, there may be an inverse relation-
ELECTROPHYSIOLOGIC
TESTING
during the refractory period and the duration calculated to result in a single capture. If the termination zone immediately follows the end of the refractory period, a train of 10 stimuli will ensure early capture and termination. Multiple captures for tachycardia termination. 393-395In some patients, interruption of the reentrant circuit or overdrive suppression may require several consecutive captures at periods above the tachycardia. Bursts of rapid pacing are usually more effective than underdrive, overdrive, or the tune-down method described below. Overdrive pacing for tachycardia termination.379,393-395,42”425 Classical overdrive pacing rates are slightly in excess of the tachycardia for several seconds to several minutes. Although there are no fixed upper limits, prolonged pacing at rates significantly above the tachycardia rate generally is not well tolerated. In some tachycardias, with Entrainment.28’ pacing rates slightly in excess of the tachycardia, entrainment results in an ECG complex that resembles either the tachycardia or some degree of fusion rather than a typical paced configuration. As the pacing rate is increased to a critical rate, entrainment ceases, and the ECG complex undergoes an abrupt change to a purely paced configuration. In some cases, cessation of pacing at this point is followed by termination of the tachycardia. The entrainment technique has proved particularly useful in the treatment of atrial flutter. Some cases of ventricular tachycardia also follow this sequence. Permanent pacers are rarely used for entrainment (Fig. 24). Tune-down or decremental ramp technique. 394,39s,440Sudden cessation of overdrive pacing may result in the reinitiation of tachycardia. Some of these patients can be successfully managed by slowing the pacing rate gradually to more physiologic rates before the pacemaker is turned off. Burst pacing (Fig. 24).393 An arbitrary but clinically useful distinction can be made between overdrive and burst pacing, which may be defined as approximately 4-l 5 stimuli at rates of 30 bpm or more faster than the tachycardia. A study of 573 episodes of ventricular tachycardia suggested that bursts of rapid ventricular pacing were more effective than programmed extrastimuli or overdrive. Acceleration of the tachycardia can occur, however, as with other methods of
Fig. 24. Rapid ventricular pacing for termination of ventricular tachycardia (VT). (Al VT at 125 bpm with a right bundle, right axis deviation configuration. Ventricular pacing was initiated at a rate just below that of the tachycardia. The pacing rate was gradually increased to 194 bpm, with capture at 143 bpm. but the tachycardia was not terminated. At 143 bpm. the QRS configuration was right bundle, left axis, i.e., a fusion between the VT configuration and the left bundle, left axis seen with “pure” pacing from this right ventricular apical site. When such fusion or “entrainment” occurs, it is almost necessary to pace at faster rates to get beyond the zone of entrainment and achieve a purely paced configuration. In this case. 194 bpm did not prove sufficient to terminate the VT. Prolonged pacing at such rates is not well tolerated by most patients, so burst pacing was subsequently used. (6) A burst of rapid ventricular (ERVPI for 5-6 captures at 194 bpm is ineffective, but BRVP at 205 bpm for 5 captures terminates the VT. Decremental, or incremental followed by decremental ramp pacing may also prove effective in some cases (see text.)
pacing, and care must be taken to establish the safety zones of both the rate and duration of the burst.
Indications Temporary pacing. Temporary pacing for control of tachycardias is indicated when the arrhythmia recurs in spite of intensive pharmacologic therapy. There are no specific contraindications to temporary pacing, even burst pacing, for control of tachycardia, but the physician must ensure that alternative methods of termination are available, including trained personnel and equipment for direct current cardioversion. Implantable antitachycardia pacemakers. 395*4’3.420A47The Intersociety Commission on Heart Disease has modified its widely used three-letter pace code to a five-letter code, partly
68
Programmed or random extrasystoles, underdrive pacing, overdrive pacing, bursts, decremental ramps (tune down), and incremental ramps or entrainment and trains of very rapid stimuli have all been used successfully in the termination of ventricular tachycardia.393”95 Bursts of rapid ventricular pacing are probably the most effective and reliable method for termination of tachycardia. Success with burst pacing does not depend on whether the tachycardia is due to automaticity or to reentry, termination being due to overdrive suppression in the former and interruption of the circuit in the latter. Pacing for tachycardia termination will be covered in greater detail later. Endocardial mapping.266 Catheters positioned in the right ventricular inflow (the His bundle position), the right ventricular apex, the right ventricular outflow, and the coronary sinus for the posterobasilar left ventricle, together with information from the peripheral ECG, often permit a general localization of the initial point of myocardial activation during centricular tachycardia. Also sought, during NSR, is evidence of abnormal isolated (delayed, fractionated) local potentials. More detailed information can be obtained using mobile catheters in the right and left ventricle. Accuracy is further enhanced if mapping is performed during surgery rather than with catheters. pacemapping makes similar use of mobile electrodes to stimulate the ventricle in each area of the grid during a baseline sinus rhythm until the paced QRS configuration precisely mimicks that of the ventricular tachycardia.367 Mapping studies have revealed that the presence of a right or left bundle branch block pattern during tachycardia is not a safe guide to predicting the chamber of origin, especially in patients with myocardial infarctions involving the interventricular septum. Endocardial mapping also may reveal the presence of diastolic depolarizations or a continuous electrical activity that also may be used to localize the tachycardia: presumably the catheters are recording impulses that are part of the reentrant circuit, some portion of which must remain in a state of depolarization at all times during the cardiac cycle. The role and relative importance of information gained by endocardial mapping in patients not proposed for antitachycardia surgery remains undefined.
JOHN
D. FISHER
The Role of Electrophysiologic Studies in the Operative Management of Ventricular Tachycardias394-4’0 Indications for surgery. Cardiac surgery is indicated in patients whose recurrent ventricular tachycardias are resistant or refractory to medical and pacemaker therapy. Philosophical differences exist as to the definition of “resistant” or “refractory” so that the percentage of patients with recurrent ventricular tachycardia who are referred for surgery will vary widely among institutions. In addition, patients may be referred earlier if there are other indications for surgery such as angina or congenital heart disease. Intraoperative studies. Insofar as possible, mapping studies are performed with the patient normothermic and not on bypass. Epicardial mapping during sinus rhythm may reveal areas of late depolarization that will merit particular attention during tachycardia as a possible site of origin of the arrhythmia. Pacemapping may be performed at the same time as mapping during sinus rhythm; comparison of the resulting QRS complexes with those occurring during the patient’s tachycardia are helpful in localizing the site of the arrhythmia. Epicardial mapping during tachycardia again is performed with the patient at or very near to normothermia, but heart/lung bypass is usually required. The earliest site of epicardial breakthrough is noted and compared with the site estimated during pacemapping. Endocardial mapping is performed, usually through the incised aneurysm or old myocardial scar.396 Surgical techniques. (1) Aneurysmectomy with endocardial excision or stripping in the area of the tachycardia focus as determined by endocardial mapping.3969397This technique recognizes that the extent of scarring is greater on the endocardial than epicardial surface and that the majority of tachycardias probably arise in the border zone near the endocardial surface. (2) Division of the bundle branches in patients thought to have macroreentry tachycardia involving the major branches of His-Purkinje system.366 (3) Ventriculotomy at the site of the tachycardia as determined by mapping.399*400(4) Cryoblation of the tachycardia focus as determined by mapping.402 (5) Aneurysmectomy (without stripping) following mapping localization of the focus to the aneurysm.m’ (6) Aneu-
ELECTROPHYSIOLOGIC
69
TESTING
rysmectomy without mapping.403407 (7) Aneurysmectomy without mapping but with addition of encircling endocardial ventriculotomy.398 This incision surrounds the border zone and extends from endocardium through to the epicardium, in the hopes of electrically isolating any impulses arising from a tachycardia focus. (8) Coronary artery bypass grafting is done as needed with each of the above operations. In patients with a surgically resectable aneurysm or scar, surgical results are not as good if the operation is limited to coronary artery bypass alone.403V404 (9) Cervical sympathectomy or stellate ganglion block, particularly useful in patients with a long QT snydrome, not requiring open heart sur408410 gery. Surgical therResults of surgical therapy. apy appears to be useful in the control of recurrent ventricular tachycardia. Series in which mapping techniques were employed have a higher success rate, especially in achieving total remission of ventricular tachycardia. If preoperative electrophysiologic studies confirm that the tachycardia focus is in an aneurysm, intraoperative studies may not be required if encircling endocardial ventriculotomy can be
performed. In patients with massive aneurysms, the encircling ventriculotomy may encompass excessive amounts of remaining viable muscle, and in such cases, the endocardial stripping approach would be preferable. Serial Electrophysiologic Testing for the Control of Recurrent Tachycardias 349,379.382-385.390.392.394.41
I-417
Concept I. In the absence of previous tachycardia or syncope, tachycardia is rarely produced by electrophysiologic stresses including l-3 programmed estrastimuli or rapid pacing83 349,379-38’*384 (Fig. 19 and 20.) In patients with recurrent Concept II. tachycardias, it usually is possible to duplicate the rate and configuration of the spontaneous tachycardia under controlled catheterization laboratory conditions using the stresses listed (Tables 7 and under concept I 8.349.379-390,384.411417 8). Concept III. Once induced, tachycardias usually can be terminated by pacer techniques, permitting serial testing of antiarrhythmic drugs without direct current cardioversion, thus increasing patient acceptance.3491 379,393m395
Ventricular tachycardia is not induced by triple ventricular premature Fig. 19. patient with a history of syncope and right bundle branch block together with ventricular arrhythmias on several Halter monitors. Leads I. II. AVF. and Vl are electrogram and recordings from the high right atrium.
beats during ventricular left axis deviation, but displayed together with
pacing in this no evidence of the HIS bundle
JOHN
Fig. 20. capture fails
Ventricular to induce
ramp tachycardia
pacing in which in the same
the rate is rapidly patient illustrated
accelerated in Fig. 18.
Serial Electrophysiologic-Pharmacologic Testing: Protocol (Fig. 20)
See recent review in this journal. Candidates for Serial Testing Most investigators in this field agree that patients with recurrent, life-threatening tachycardias should undergo serial testing in an experienced center. Patients with recurrent nonlethal tachycardias, which have nevertheless proved 7.
Atrial
Vulnerability
to Electrophysiologic SVT
Patient
Group
bpm
or the
maximum
permitting
I:1
refractory to multiple drug trials, also are considered. Whether patients who have suffered a single episode of ventricular tachycardia not related to myocardial infarction should undergo invasive studies as yet is unsettled. Survivors of cardiac arrest will probably increasingly become sugjects for serial testing.4’4~4’5~418 Patients with acute anterior wall mycoardial infarctions and any complete bundle branch block may have as much as a 36% incidence of unheralded ventricular tachycardia or fibrillation in the 6 wk following myocardial infarction419 Survivors of myocardial infarction with more than one ventricular premature beat in response to a single programmed extrastimulus may be at dire risk of subsequent VT or sudden death.39’ These
Concept IV. The efficacy of antiarrhythmic therapy can be judged by the degree to which the normal response (concept I) to stresses is restored.349.379.382-38s. 392,41 I-417
Table
to 250
D. FISHER
Initiated/No.
Total
Stressasc”8
Patients
Tested/Percent
1 PES
2-3
SRAP
PES
Controls
6/52/12
l/52/2
4/31/13
l/3/33
suo
7129124
l/29/3
6/20/30
Of2/o
All sss
9131129
o/3
9/16/56
l/2/50
SB
4/25/16
o/25/0
4/l
1 I2150
BTS
5/6/83
O/6/0
5/6/83
o/o/o
28/40/70
10/39/26
1 S/26/69
4/6/67
SVT SVf
group,
SVT.
patients
with
supraventricular
extrastimuli;
BRAP,
brady-tachy
syndrome.
documented
tachycardia burst
of rapid
spontaneous of all types,
atrial
pacing:
1 JO
o/40
SVT. lasting
SUO,
a minimum
syncope
of several
of unknown
origin;
seconds, SSS,
and sick
sinus
excluding syndrome;
echo
beats; SE,
sinus
PES,
programmed
bradycardia;
BTS,
ELECTROPHYSIOLOGIC
TESTING
71
Table
8.
Ventricular
Vulnerability
Total
Fisher et aL3s0 (updated 8 1 Patients
BRVP/RAMPS
%
VT
Att
%
VT
Att
%
VT
Att
%
VT
79
82
96.3
14
81
17.3
27
69
39.1
36
45
80.0
11
4
15
26.7
0
15
0.0
1
14
7.1
3
11
27.3
14
51
27.5
2
51
3.9
3
48
6.3
10
42
5
105
0
105
0.0
1
53
1.9
4
40.3
16
252
6.3
Att
Other %
VT Att
%
to 3/80) 18
61.1
4
4
100.0
1
8
12.5
0
2
23.8
0
25
0.0
1
3
35
11.4
0
15
0.0
0
3
18.2
5
12
0.0
4.8
33.3 0.0
pts) 102
(57 pts) Nonsustained
253
32
184
17.4
53
133
39.8
12
66
41.7
23
-
-
-
-
-
12
5422
--
-
13
-
-
-
-
-
5
2917
--
-
126
2.3-
-
-
0 443
studies)
VT
(29 pts) Control
54
57
95
19
18
29
62
4
3
443
0.7
57
35
2914
0 443
0
3
0
-
-
-
pts)
Att = Patients with VT induction PES = Programmed extrastimuli. VT = Vantrtcular tachycardia. 8RVP Other
3 PES
pt.4
(252 pts, 254 Vandepol et aL3” Sustained VT
(443
2 PES
Att
(51 pts) Control (105 Total
1 PES
Stresses
VT
(83 studies) Former VT (15 suo
to Electrophysioligc
= Bursts = Addition
pt = Patients. SUO = Syncope
attempted.
of rapid ventricular of isooroterenol, of unknown
pacing. with or without
PES; inhibition
pacer,
etc.
origin.
patients are potential candidates for serial electrophysiologic-pharmacologic testing. Some investigators have reported that it is difficult to induce a tachycardia in the Catheterization Laboratory in patients with exerciserelated tachycardias.378 We have not found this to be the case. Electrophysiologic
of permanent
Testing (Fig. 21)
Whenever possible, antiarrhythmic drugs are discontinued for a substantial period of time prior to the test. From 24 to 48 hrs, or five drug half-lifes have been used as guides to timing the discontinuation of drugs prior to testing. In patients with incessant tachycardias, it may be wise to initiate testing while the patient is on a regimen that results in acceptable toleration of the tachycardia. Step 1. Attempts are made to induce the tachycardia using programmed extrastimuli, rapid atria1 or ventricular pacing, and other techniques. Step II. Once tachycardia has been induced, the patient’s hemodynamic status is evaluated immediately. If the tachycardia is well tol-
erated, rate, configuration, depolarization sequence, and diagnosis or type are analyzed. If the ventricular rate is rapid or the hemodynamits are not stable, the tachycardia is terminated as rapidly as possibleusing pacer techniques or DC cardioversion. Step III. Oral or intravenous medications are given, the choice depending on the type of tachycardia, the patient’s history, agents of particular interest to the investigator, and the appropriateness of an agent for the tachycardia being studied. If tachycardia is reinitiated, another drug may be added to the first and the sequencerepeated. Step IV. Subsequent days. A temporary pacemaker electrode is left in place from the first day of study in the position most effective in initiating and terminating the tachycardia. If a promising agent was found during the initial studies, the patient is retested for confirmation on an oral regimen. Drug blood levels should be obtained during initial studies and during serial testing to ensurethat a given drug has received a fair trial and to establish guidelines for future therapy.
72
JOHN
D. FISHER
SERIALELECTROPHYSIOLOGIC-PHARK4COLOGIC TESTING ATTEMPT TACHYCARDIA INDUCTION WITHELECTROPHYSIOLOGIC STRESSES NOTACHYCARDIA-TACHYCARDIA = NOVULNERABILITY =VULNERABLE PACERTERMINATION r NOTPOSSIBLEIPOSSIBLE iiiTzz?= ADMINISTERDRUGSINTRAVENOUSLY AGAINATTEMPT TICHYCARDIAINDUCTION NOTPOSSIBLE t
POSSIBLE
BEGIN ORALEQUIVALENT t RE-TESTUSINGTEMPORARY WIRE LEFT IN PLACEAFTER INITIAL DAY’S TESTING
TERMINATE
NORELIABLEPACER-I TERMINATION t SURGERY,PSYCH ETC,
End points in serial testing. Ideally, a regimen eventually is identified on which it is impossible to reinitiate the patient’s tachycardia. Partial protection implies that the tachycardia zone has become narrower, the rate slower, the hemodynamics improved, or reliable termination by an implanted pacer is possible. The only way available at present to assess whether pacing is efficacious, is to record several 24-hr Holter monitors during spontaneous and during paced rhythm, observing the relative incidence of pauses and premature beats. Indeed, serial Holter monitors during the course of serial electrophysiologic testing may add an important dimension to the assessment of therapy. Alternatives: Pacing and surgery. Pacing for termination rather than prevention represents the pound of cure rather than the ounce of prevention, but seems certain to play an increasing role in the future therapy of arrhythmias. The value of cardiac surgery is also increasing. results
OfSerial
Testing349.379,38~38’,392,411~17
Serial electrophysiologic-pharmacologic testing for the control of recurrent tachycardias has
-qADDOTHERDRUG(S) NOFULLYPROTECTIVE DRUGSIDENTIFIED RELIkLE PACER
IMPliVrTED ANTITACHYCARDIA PACER
Fig. 21. Serial tasting scenerio. Flow diagram of sequanta used during serial alactrophysiologic pharmacologic testing for control of recurrent tachycardias. The actual point at which surgical or implanted pacemaker therapy would be chosen will depend on the characteristics of the patient undergoing study, and the axpartisa of the institution or referral center.
been reported from several centers. The procedure has proved remarkably safe, considering the arrhythmias induced and the incidence of major complications including death, cerebrovascular accident, and myocardial infarctions has been exceedingly small. Reduction of the number and duration of hospital admissions after serial testing brings savings in hospital costs and work days lost. The psychologic benefits to the patient who is relieved of a “sword of Damocles” are manifest. Pacing in the Treatment Tachycardia
of Recurrent
Progress in electrophysiologic testing techniques has contributed to major advances in the pacer treatment of tachycardias. Several pacing techniques have proven useful for temporary and long-term pacing. Tachycardia Prevention379’394’395 Rate support.420V42’ In the presence of profound bradycardia, atria1 and ventricular tachycardias may develop as escape rhythms. Such patients would ordinarily receive pacemak-
ELECTROPHYSIOLOGIC
73
TESTING
present during regular supraventricular tachycardia. While implanted units have been adapted for permanent rapid atria1 pacing,426 the technique most often is on a temporary basis following open heart surgery.427 Paired and coupled pacing.428-430 In paired pacing, an initial stimulus (Sl) is followed by a second stimulus (S2), with the SlS2 interval being shorter than the S2Sl interval. In coupled pacing, the patient’s natural depolarization acts as the Sl and a pacer stimulus as S2. When used in the ventricle, the S2 is timed to produce an electrical, but not a mechanical response.
ers for treatment of bradycardia, and prevention of tachycardia is a secondary benefit. Overdrive suppression.422425 Pacing at rates slightly in excess of a normal rhythm may help to reduce the number of premature beats if they are associated with the initiation of tachycardia. Occasionally, rates of 90-l 10 bpm are required, acutely and chronically, for suppression of tachycardia, and rarely, rates as high as 150 bpm may be needed. During electrophysiologic studies it is common that tachycardia initiation is more difficult during sinus or atria1 rhythms than during ventricular pacing. Implanted atria1 pacemakers may, therefore, be advantageous when used for prevention of ventricular tachycardia. Rate Control Without Termination425430
Pacing for Tachycardia Termination379*395 Single Capture Tachycardia Termination Slow competitive or “underdrive” pacing is useful primarily in patients whose tachycardias have a wise termination zone for a single stimu1~s~~~ (Fig. 22). Conventional AA1 and VVI demand pacemakers can be used, activated by placing a magnet over the unit. Dual demand pacemakers (single chamber slow competitive type)43’ operate as standard demand pacemakers in a bradycardia prevention
Tachycardia
Continuous rapid pacing.425427 In patients with incessant supraventricular tachycardias, reduction in ventricular rate can be achieved by rapid atria1 pacing at a rate that results in 2:1 AV conduction. Induced atria1 fibrillation may result in a slower ventricular rate than was
I
'1
Fig. 22. Termination of ventricular tachycardia by underdrive pacing or single programmed extrastimuli. Peripheral leads I, II, AVF, and Vl are displayed together with the His bundle electrogram and recordings from the low lateral right atrium and the right ventricular outflow, where premature beats are given at the points designated by the arrows. Eventually, the techycardia is terminated. The right ventricular pacing was in the form of programmed extrastimuli, but underdrive pacing would have a similar appearance.
74
JOHN
Table
9.
Dual
Chamber
Pacing
(Tachycardiaj-’ Pacing
Special VAT, OP*
Pacer
HR (bpml
(Devices)
DDD,
<150(V) 2150 (VI < 124 (A,V)
ON (Medtronic)
124-185(A) > 185 (A) l P: Nonstandard HR. heart
rate;
code bpm,
for prevention beats
per minute;
(in these
by rendering
Rate AV Interval
(bpm)
All All
DDT, OP’ (Medtronic) DVI, MN (Medtronic)
reentry
D. FISHER
circuit
lsorhythmic
30 msec
lsorhythmic DVI 77
Simultaneous Programmable 65 msec
(Isorhythmic) V: l/2 A rate
180 180
msec msec
73
180
msec
refractory).
code
is after
ICHD
(Fig. 26).
AV. atrioventricular.
role. With the onset of tachycardia, they are activated automatically, emit stimuli at the same rate as their conventional demand rate, and continue to pace until they sense the termination of the tachycardia. Upside-down demand pacemakers have no conventional demand role, but do respond with slow competitive pacing in the event of a tachycardia.432 Dual chamber pacers. Some AV nodal reentrant tachycardias or tachycardias related to the Wolff-Parkinson-White syndrome can be terminated most reliably by simultaneous or nearly simultaneous atria1 and ventricular stimulation, which can be accomplished by modified AV sequential (DVI) or atria1 synchronous pacemakers (VAT,DDT)433A36 (Table 9). Autoscan pacemakers.437 To minimize the delay in termination associated with fixed rate underdrive pacing, these proceed, in a variety of
Fig. 23. Termination of ventricular tachycardia displayed together with a right ventricular recording. train of 10 stimuli with a cycle length of 7.5 msec.
by a train Ventricular
orderly programs, to scan the diastolic period of the tachycardia with premature beats. Orthorhythmic pacing.438 The orthorhythmic pacemaker (Savita) is a multicapable tabletop unit designed for automatic termination or prevention of tachycardia. The unit can be programmed to perform underdrive pacing either at a fixed rate or at a percentage of the tachycardia cycle length. The orthorhythmic pacemaker has enjoyed some success in an “abort” mode, programmed to insert one or more stimuli immediately after spontaneous extrasystoles to abort the development of a sustained tachycardia. Trains.‘94,439 A short train (Fig. 23) of extremely rapid stimuli with cycle lengths of 2-40 msec provides another approach to the problem of a very narrow tachycardia termination zone. The onset of the train is timed to begin
of ultrarapid tachycardia
stimulation. at a cycle
ECG leads, I. II. AVF. and length of 410 msec is terminated
Vl
are by a
ELECTROPHYSIOLOGIC
TESTING
during the refractory period and the duration calculated to result in a single capture. If the termination zone immediately follows the end of the refractory period, a train of 10 stimuli will ensure early capture and termination. Multiple captures for tachycardia termination. 393-395In some patients, interruption of the reentrant circuit or overdrive suppression may require several consecutive captures at periods above the tachycardia. Bursts of rapid pacing are usually more effective than underdrive, overdrive, or the tune-down method described below. Overdrive pacing for tachycardia termination.379,393-395,42”425 Classical overdrive pacing rates are slightly in excess of the tachycardia for several seconds to several minutes. Although there are no fixed upper limits, prolonged pacing at rates significantly above the tachycardia rate generally is not well tolerated. In some tachycardias, with Entrainment.28’ pacing rates slightly in excess of the tachycardia, entrainment results in an ECG complex that resembles either the tachycardia or some degree of fusion rather than a typical paced configuration. As the pacing rate is increased to a critical rate, entrainment ceases, and the ECG complex undergoes an abrupt change to a purely paced configuration. In some cases, cessation of pacing at this point is followed by termination of the tachycardia. The entrainment technique has proved particularly useful in the treatment of atrial flutter. Some cases of ventricular tachycardia also follow this sequence. Permanent pacers are rarely used for entrainment (Fig. 24). Tune-down or decremental ramp technique. 394,39s,440Sudden cessation of overdrive pacing may result in the reinitiation of tachycardia. Some of these patients can be successfully managed by slowing the pacing rate gradually to more physiologic rates before the pacemaker is turned off. Burst pacing (Fig. 24).393 An arbitrary but clinically useful distinction can be made between overdrive and burst pacing, which may be defined as approximately 4-l 5 stimuli at rates of 30 bpm or more faster than the tachycardia. A study of 573 episodes of ventricular tachycardia suggested that bursts of rapid ventricular pacing were more effective than programmed extrastimuli or overdrive. Acceleration of the tachycardia can occur, however, as with other methods of
Fig. 24. Rapid ventricular pacing for termination of ventricular tachycardia (VT). (Al VT at 125 bpm with a right bundle, right axis deviation configuration. Ventricular pacing was initiated at a rate just below that of the tachycardia. The pacing rate was gradually increased to 194 bpm, with capture at 143 bpm. but the tachycardia was not terminated. At 143 bpm. the QRS configuration was right bundle, left axis, i.e., a fusion between the VT configuration and the left bundle, left axis seen with “pure” pacing from this right ventricular apical site. When such fusion or “entrainment” occurs, it is almost necessary to pace at faster rates to get beyond the zone of entrainment and achieve a purely paced configuration. In this case. 194 bpm did not prove sufficient to terminate the VT. Prolonged pacing at such rates is not well tolerated by most patients, so burst pacing was subsequently used. (6) A burst of rapid ventricular (ERVPI for 5-6 captures at 194 bpm is ineffective, but BRVP at 205 bpm for 5 captures terminates the VT. Decremental, or incremental followed by decremental ramp pacing may also prove effective in some cases (see text.)
pacing, and care must be taken to establish the safety zones of both the rate and duration of the burst.
Indications Temporary pacing. Temporary pacing for control of tachycardias is indicated when the arrhythmia recurs in spite of intensive pharmacologic therapy. There are no specific contraindications to temporary pacing, even burst pacing, for control of tachycardia, but the physician must ensure that alternative methods of termination are available, including trained personnel and equipment for direct current cardioversion. Implantable antitachycardia pacemakers. 395*4’3.420A47The Intersociety Commission on Heart Disease has modified its widely used three-letter pace code to a five-letter code, partly
76
JOHN
to cope with the profusion of antitachycardia pacers446 (Fig. 25). The indications for implantable pacemakers for the control of tachycardias are more strict in order to avoid the acceleration of a ventricular tachycardia, which may prove catastrophic. For reasonable security, scores of episodes should be terminated reliably preimplantation, using a temporary pacemaker with implantation parameters, under a variety of conditions, i.e., peak and trough blood drug levels, different body positions, and varying times of the day and night. The safest approach for patients who tolerate the arrhythmia well may be implantation of a manually activated unit that can be used after the patient arrives in the emergency room, with electrocardiographic confirmation of the tachycardia and with direct current cardioversion available. Automatic pacemakers may be appropriate in patients who rapidly develop syncope or hemodynamic decompensation with their tachycardias, or who have very frequent episodes of the arrhythmia. Other candidates include patients who are unaware of the presence of tachycardia prior to hemodynamic decompensation. Some patients are unable to cope psychologically with the responsibilities of a manual system, and such patients may benefit from an automatic pacemaker.
Automatic
implanted
trode mesh capping the apex of the heart, implanted through a left thoracotomy. Unlike regular tachycardias, many forms of ventricular fibri11ation37’*447 are characterized by chaotic wave forms without isoelectric potential segments. In addition to a conventional sensing circuit, the implantable defibrillator senses the absence of isoelectric periods and after approximately 15 set, emits a truncated exponential pulse of up to 30 joules. After extensive development and animal trials, implantations have begun in humans with refractory recurrent ventricular fibrillation and rapid ventricular tachycardia. Syncope of Unknown
defibrillators.447
1
2
3
4
5
CATEGORY
Chambsr(s) Paced
Chamber(s) sensed
Mode of Responss(s)
Programmable FUnctions
Speciil ahythmia
Letters Used
V-venwck
V-vantrlck
T-Triggared
P- Programin&Is (Flate&lbr Outpra
B-Bursts
A-Atrium
A-Atrium
I-lnhibitii
M-multiprogrammable
N-Normal Competition
D-Double
D-mle
D-Double*
o-Nma
S-Scanning
O-None
o-Ncms
E-External
R-REVSlfW
L * Atrial
triggered
and
ventricular
inhibited
Origin (SUO)
The clinician is called upon often to deal with the problem of a patient with syncope or other neurologic symptoms, the etiology of which remains unexplained after a thorough medical and neurologic work-up. Such a work-up should include a detailed medical and pharmacologic history, pertinent blood chemistries and drug levels, neurologic consultation with appropriate studies, physical maneuvers including hyperventilation, carotid sinus massage, evaluation for orthostatic hypotension, maneuvers of the neck to evaluate the possibility of boney or atheromatous obstruction to cerebra1 blood flow, and prolonged ECG (Holter monitoring). Patients who “pass” this noninvasive workup may be designated as having “syncope of unknown
Present implantable defibrillators consist of a transvenous electrode introduced into the superior vena cava, and an extrapericardial elec-
POSITION
D. FISHER
TachyFunctkx
Rate
Fig. 25. Five position pacemaker code (Intersociety Commission on Heart Disease).W The original three position code has gained widespread acceptance, but the growth of programmability and antitachycardia pacing has led to the addition of two more positions. A conventional ventricular inhibited demand pacer would be coded as VVI: the addition of multiprogrammability would render it a VVLMO: A burst pacing capability for treatment of tachycardia would change the designation to VVLMB. (This illustration will soon be published simultaneously in several journals. Used here by permission of authors and PACE).
ELECTROPHYSIOLOGIC
77
TESTING
origin,” and may be appropriate candidates for electrophysiologic testing. Patients who meet this definition of SUO and who are found to have a prolongation of the H-V interval appear to benefit from permanent pacing.‘85 It is possible to induce supraventricular tachycardias in approximately 24% of patients with SUO (Table 7) .448 While supraventricular tachycardias can result in sudden hypotension and syncope, the 12% rate of tachycardia induction in a control group (Table 7) suggests the possibility of a significant number of false positive tests among SUO subjects. Ventricular tachycardia also can be induced in about a quarter of patients with SUO (Table S), but only in 0.7%-4.8% of Induction of ventricular tachycarcontrols.380*38’ dia thus constitutes a significant finding during electrophysiologic testing. A recent seriesof 92 patients with syncope of unknown origin, the majority of whom had Holter monitoring, exercise testing, and neurologic examinations, but not baseline carotid sinus massage,suggestedthat electrophysiologic testing could establish the probable cause of syncope in approximately 64%.448Of these 92 patients, 11 were found to have carotid sinus hypersensitivity, 10 ventricular arrhythmias, 9 supraventricular arrhythmias, and 5 sinus node dysfunction. The 54 patients in whom a causefor syncope was determined on the basisof electrophysiologic tests were treated accordingly, and after being followed up for 14.2 mo, 38 patients (89%) remained free of further syncope, and 2 patients had been improved. Electrophysiologic testing may not be able to help in the diagnosisof syncope due to intermittent profound hypervagotonia, sudden withdrawal of sympathetic tone,450and some other dynamic or intermittent states, such as prolonged Q-T interval syndromes and coronary artery spasm. Some patients with grand ma1 seizures may have normal neurologic examinations and thus escapeidentification. For many of these conditions, the importance of a detailed history and physical examination and prolonged
ECG monitoring are vital in making the diagnosis. OVERVIEW
The present role of clinical electrophysiologic testing is somewhat different from that anticipated a decade ago. Early hopes that simple sinus node function tests and the measurement of conduction intervals would provide reliable guidelines for the implantation of permanent pacemakers have been dashed on the rocks of complexity. Although progress has been made, accurate assessmentof risk in patients with suspected bradycardia remains an elusive goal. Stunning advances have been made in the diagnosis and treatment of tachycardias. Electrophysiologic testing has permitted detailed characterization of many tachycardias, and has identified previously unsuspectedmechanisms.Some of this information is directly translatable for use as guidelines by the clinical cardiologist. Electrophysiologic studies have permitted a quantum leap in the treatment of tachycardias in four important ways: (1) Analysis of the electrophysiologic characteristics of a tachycardia aids in assessingthe risk to the patient and in identifying possible“weak links” in the circuit to which pharmacologic or pacer therapy may be directed. (2) The technique of serial electrophysiologic pharmacologic testing provides a basis for an orderly and objective assessmentof drug efficacy. (3) The ability to reproducibly initiate and terminate tachycardias has resulted in the development of a rapidly increasing array of antitachycardia devices, some of which are implantable and operate automatically. (4) The effectiveness of antitachycardia surgery has been clearly enhanced by the use of preoperative and intraoperative ‘electrophysiologic studies. Electrophysiologic testing has appeared to have earned its place in the diagnostic and therapeutic repertoire. Investigators continue to be challenged by new concepts, findings, and applications for their technique, all of which promise continuing progressin the years to come.
REFERENCES 1. NarulaOS: His bundle Electrocardiography and Clinical Electrophysiology. Philadelphia, FA Davis, 1975 2. Krikler DM, Goodwin JF: Cardiac Arrhythmias: The Modern Electrophysiologic Approach. London, WB Saunders, 1975
3. Wellens HJJ, Lie Kl, Janse MJ: The Conduction System of the Heart. Structure, Function and Clinical implications. Philadelphia, Lea & Febiger, 1976 4. Kulbertus HE: Re-entrant Arrhythmias. Mechanisms and Treatment. Baltimore, University Park Press, 1977
78
JOHN
5. Narula OS: Cardiac Arrhythmias: Electrophysiology, Diagnosis and Management., Baltimore, Williams & Wilkins, 1979 6. Josephson ME, Seides SF: Clinical Cardiac Electrophysiology. Techniques and Interpretations. Philadelphia, Lea & Febiger, 1979 7. Series on Sudden Cardiac Death: Series on Cardiac Pacing. Prog in Cardiovasc Disease, Vol 23 and 24, 19801981 8. Fisher JD: Clinical Electrophysiologic Testing. Medication, Surgery, and Pacemakers for Arrhythmia Control, in Resnekov L, Julian D (eds): Friedberg: Diseases of the Heart (ed 4). New York, Churchill Livingston, (in press) 9. Flowers NC, Hand RC, Orander PC, et al: Surface recording of electrical activity from the region of the His bundle. Am J Cardiol 33:384-389, 1974 10. Berbari EJ, Lazzara R, El-Sherif N, et al: Extracardisc recordings of His-Purkinje activity during conduction disorders and junctional rhythms. Circulation 51:802-810, 1975
I 1. Furness A, Sharratt GP, Carson P: The feasibility of detecting His-bundle activity from the body surface. Cardiovast Res 9:390-396, 1975 12. Wajszczuk WJ, Stopczyk MJ, Moskowitz MS, et al: Noninvasive recordings of His-Purkinje activity in man by QRS-triggered signal averaging. Circulation 58:95-102, 1978
13. Fisher JD, Kay M, Mehra R, et al: Increased accuracy of the corrected H-V time, in Meere (ed): Proceedings of the VI World Symposium on Cardiac Pacing. Montreal, Pacesymp, 1979 14. Decaprio V: Endocardial electrograms from transvenous pacemaker electrodes. PhD Dissertation. Polytechnic Institute of Brooklyn. University Microfilms, 1977 15. Damato AN, Lau SH, Helfant RH, et al: Study of atrioventricular conduction in man using electrode catheter recordings of His bundle activity. Circulation 39:287-296, 1969 16. Damato AN, Lau SH, Helfant RH, et al: A study of heart block in man using His bundle recordings. Circulation 391297,
1969
17. Narula OS, Cohen LS, Samet P, et al: Localization of A-V conduction defects in man by recording of the His bundle electrogram. Am J Cardiol 25:228, 1970 18. Gallagher JJ, Damato AN, Lau SH, et al: Antecubital vein approach for recording His bundle activity in man. Am Heart J 85:199-204, 1973 19. Narula OS, Runge M, Samet P: A new catheter technique for His bundle recordings via the arm veins. Br Heart J 45:1226, 1973 20. Josephson ME, Seides SF: Electrophysiologic investigation: technical aspects, in Josephson ME, Seides SF (eds): Clinical Cardiac Electrophysiology: Techniques and Interpretations. Philadelphia, Lea & Febiger, 1979, p 17-18 21. Escher DJW, Furman S, Fisher JD, et al: Temporary pacing in the treatment of arrhythmias, in Watanube Y (ed): Cardiac Pacing. Proceedings of the V International Symposium, Tokyo. Amsterdam, Excerpta Medica, 1977, pp 153161 22. Fisher JD: His bundle studies during pullout of standard temporary pacing leads. Clin Res 25:648A, 1977
0. FISHER
23. Meister SG, Banka VS, Chadda KD, et al: A balloon tipped catheter for obtaining His bundle electrograms without 24. Moore EN, Spear JF: Effect of autonomic activity on pacemaker function and conduction, in Wellens, Lie, Janse (eds): The Conduction System of the Heart. Philadelphia, Lea & Febiger, 1976, pp IO&l 10 25. Martin P: The influence of the parasympathetic nervous system on atrioventricular conduction. Circ Res 411593-599,
1977
Jewel1 GM, Magorien RD, manic tone of patients during an terization. Am Heart J 99:51-57, 27. Dhingra RC, Rosen KM, conduction intervals and responses His bundle recording and atria1 26.
Schaael SF, et al: Autonoelectrophysiological cathe1980 Rahimtoola SH: Normal in sixty-one patients using pacing. Chest 64:55-59,
1973 28. Narula OS, Scherlag BJ, Samet P: Pervenous pacing of the specialized conducting system in man. Circulation 41:77, 1970 29. Narula OS: Validation of His bundle recordings: Limitations of the catheter technique in Narula OS (ed): His Bundle Electrocardiography and Clinical Electrophysiology. Philadelphia, FA Davis, 1975, pp 65-93 30. Narula OS: Longitudinal dissociation in the His bundle. Bundle branch block due to asynchronous conduction within the His bundle in man. Circulation 56:996-1006, 1977 3 1. El-Sherif N, Amat-Y-Leon F, Schonfield C: Normalization of BBB patterns by distal His bundle Pacing:Clinical and experimental evidence of longitudinal dissociation in the pathologic His bundle. Circulation 57:473483, 1978 32. Scheinman MM, Peters RW, Modin G, et al: Prognostic value or infranodal conduction time in patients with chronic bundle branch block. Circulation 56:240-244, 1977 33. McAnulty JH, Rahimtoola Sh, Murphy ES, et al: A prospective study of sudden death in “high-risk” bundlebranch block. N Engl J Med 299:209-215, 1978 34. Altschuler H, Fisher JD, Furman S: Significance of isolated H-V interval prolongation in symptomatic patients without documented heart block. Am Heart J 97: 19, 1979 35. Dhingra RC, Denes P, Wu D, et al: Prospective observations in patients with chronic bundle branch block and market H-V prolongation. Circulation 53:60@-604, 1976 36. Rosen KM, Rahimtoola SH, Chuquimia R, et al: Electrophysiological significance of first degree atrioventricular conduction disturbance. Circulation 43:491, 1971 37. Goldreyer BN, Weiss MB, Damata AN: Supraventricular tachycardia initiated by sinus beats. Circulation 44:830, 38.
197 1
Naruia OS: Electrophysiology of normal impulse propagation, in Narula OS (ed): Cardiac Arrhythmias, Electrophysiology, Diagnosis and Management. 1979, pp 57-65 39. Weiss S. Baker JP: The carotid sinus reflex in health and disease. Its role in the causation of fainting and convulsions. Medicine 12:297-354, 1933 40. Galdston M, Goldstein R, Steele MJ: Studies of the variation in circulatory and respiratory reponses to carotid sinus stimulation in man. Am Heart J 26:213-23 1, 1943 41. Sigler LH: Clinical observations on the carotid sinus
ELECTROPHYSIOLOGIC
TESTING
reflex 1. The frequency and the degree of response to carotid sinus pressure under various diseased states. Am J Med Sci 186:11(rllS, 1933 42. Sigler LH: Clinical observations on the carotid sinus reflex. II. The response to carotid sinus pressure at various ages and heart rates and rhythms. Am J Med Sci 186:118125,1933 43. Sigler LH: Further observations on the carotid sinus reflex. Ann Intern Med 9:1380-1392, 1936 44. Heidorn GH, McNamara AP: Effect of carotid sinus stimulation on the electrocardiograms of clinically normal individuals. Circulation 14:1104-l 113, 1956 45. Sigler LH: The cardioinhibitory carotid sinus reflex. Its importance as a vagocardiosensitivity test. Am J Cardiol 12:175-183,1963 46. Hartzler GO, Maloney JD: Cardioinhibitory carotid sinus hypersensitivity. Intracardiac recordings and clinical assessment. Arch Intern Med 137:727-731, 1977 47. Davies AB, Stephens MR. Davies AG: Carotid Sinus Hypersensitivity in patients presenting with syncope. Br Heart J 42:583-586, 1979 48. Fisher JD, Katz G, Furman S, et al: Differential responses to carotid sinus massage in cardiac patients with and without syncope. Clin Res (in press) 49. Hutchinson EC, Stock JPP: The carotid-sinus syndrome. Lancet 2:445-449,1960 50. Stevenson CA: The use of roentgen therapy in the carotid sinus syndrome. Radiology 32:209, 1939 5 1. Voss DM, Magnin GE: Demand pacing and carotid sinus syncope. Am Heart J 79:544-547, 1970 52. Walter PF, Crawley IS, Dorney ER: Carotid sinus hypersensitivity and syncope. Am J Cardiol 42:396-403, 1978. 53. Chughtai AL, Yans J, Kwatra M: Carotid sinus syncope. JAMA 237:2320, 1977 54. Cohen MV: Ventricular fibrillation precipitated by carotid sinus pressure: Case report and review of the literature. Am Heart J 84:681-686, 1972 55. Alexander S, Ping WC: Fatal ventricular fibrillation during carotid sinus stimulation. Am J Cardiol 18:2899291, 1966 56. Jonas EA, Kosowsky BD, Ramaswamy K: Complete His-Purkinje block produced by carotid sinus massage. Report of a case. Circulation 50:192-197, 1974 57. Narula OS: Disorders of sinus node function, in Narula OS (ed): Electrophysiologic Evaluation. His Bundle Electrocardiography and Clinical Electrophysiology. Philadelphia, FA Davis, 1975, pp 275-3 11 58. Lown B, Levine SA: The carotid sinus. Clinical value of its stimulation. Circulation 23:766-788, 1961 59. Bakst A, Goldberg B, Schamroth L: Significance of exercise-induced second degree atrioventricular block. Br Heart J 37:984986, 1975 60. Fisher JD: Unpublished Data 61. Tilkian Ag, Guilleminault C, Schroeder JS, et al: Sleep-induced apnea syndrome: Prevalence of cardiac arrhythmias and their reversal after tracheostomy. Am J Med 63:348-358, 1977 62. Kerin NZ, Edelstein J, Goldberg LB, et al: Cardiac dysrhythmias associated with obesity and sleep apnea. Cardiovasc Med 4:1167-l 172, 1979
79 63. Engel GL: Sudden and rapid death during psychological stress. Folk lore or folk wisdom. Ann Intern Med 74:771782,197l 64. Narula OS: Electrophysiology of normal impulse propagation, in Narula OS (ed): Cardiac Arrhythmias: Electrophysiology, Diagnosis and Management. Baltimore, Williams & Wilkins, 1979, p 57 65. Narula OS: Current concepts of atrioventricular block, Narula OS (ed): His Bundle Electrocardiography and Clinical electrophysiology. Philadelphia, FA Davis, 1975, p 139 66. Goodman LS, Gilman A: The Pharmacological Basis of Therapeutics (ed 6): New York, Macmillan, 1980 67. Lucchesi BR: Antiarrhythmic drugs: Key references. Circulation 59:1076-1078, 1979 68. Bigger JT Jr, Dresdale RJ, Heissenbuttel RH, et al: Ventricular arrhythmias in ischemic heart disease: Mechanism, prevalence, significance and management. Prog Cardiovasc Dis19:255-300, 1977 69. Singh BN, Collett JT, Chew CYC: New perspectives in the pharmacologic therapy of cardiac arrhythmias. Prog Cardiovasc Dis 22:243-301, 1980 70. Singh BN, Hauswirth 0: Comparative mechanisms of action of antiarrhythmic drugs. Am Heart J 87:367-382, 1974 7 1. Rosen MR, Wit AL, Hoffman BF: Electrophysiology and pharmacology of cardiac arrhythmias. Am Heart J Vol 88-90, 1974-1975 72. Zipes DP, Troup PJ: New antiarrhythmic agents: Am J Cardiol41:1005, 1978 73. Singh BN, Hauswirth 0: Comparative mechanisms of action of antiarrhythmic drugs. Am Heart J 87:367-382, 1974 74. Sami M, Mason JW, Peters F, et al: Clinical electrophysiologic effects of encainide, a newly developed antiarrhythmic agent. Am J Cardiol44:526-532, 1979 75. Sami M, Mason JW, Oh G, et al: Canine electrophysiology of encainide, a new antiarrhythmic drug. Am J Cardiol43:114991154, 1979 76. Bussmann W-D, Muller E, Hanel H-J, et al: Orally administered prajmalium bitartrate in acute and chronic ventricular arrhythmias. Am J Cardiol41:577-583, 1978 77. Fenici R, Marchei M, Bellocci F, et al: Effect of bunaphtine on right atria1 repolarisation in man. Br Heart J 39:787-794, 1977 78. Wellens HJJ, Bar FW, Gorgels AP, et al: Use of ajmaline in patients with the Wolff-Parkinson-White syndrome to disclose short refractory period of the accessory pathway. Am J Cardiol45:130-133, 1980 79. Gould L, Reddy CVR, Oh K-C, et al: Electrophysiologic properties of steroids in man. Curr Concept Pacing 1:6-17. 1978 80. Whipple GH: Papaverine as an antiarrhythmic agent. Angiology 28:737-749, 1977 8 1. Fowler NO, McCall D, Chou T-C, et al: Electrocardiographic changes and cardiac arrhythmias in patients receiving psychotropic drugs. Am J Cardiol 37:223-230, 1976 82. Gettes LS: On the classification of antiarrhythmic drugs. Modern Conept Cardiovasc Dis 48: 13-l 8, 1979
80 83. Gettes LS: The electrophysiologic effects of antiarrhythmic drugs. Am J Cardiol28:526-535, I97 1 84. Rosen MR, Hoffman BF: Mechanisms of action of antiarrhythmic Drugs. Circ Res 32:l-8, 1973 85. Harrison DC, Meffin PJ, Winkle RA: Clinical pharmacokinetics of antiarrhythmic drugs. Prog Cardiovasc Dis 20:217-242, 1977 86. Bigger JT Jr: Pharmacologic and clinical control of antiarrhythmic drugs. Am J Med 58:479-488, 197.5 87. Gibaldi M, Perrier D: Pharnacokinetics, in Swarbrick J (ed): Drugs and the Pharmaceutical Sciences, Vol 1. New York, Marcel Dekker, 1975 88. Greenblatt DJ, Bolognini V, Koch-Weser J, et al: Pharmacokinetic approach to the clinical use of lidocaine intravenously. JAMA 236:273-277, 1976 89. Wellens HJJ, Bar FWHM, Lie KI, et al: Effect of procainamide, propranolol, and verapamil on mechanism of tachycardia in patients with chronic recurrent ventricular tachycardia. Am J Cardiol40:579-585, 1977 90. Ferrer MI: The Sick Sinus Syndrome. New York, Futura, 1974 91. Narula OS: Sick sinus syndrome: Key References. Circulation 60:1422-1424, 1979 92. Scarpa WJ: The sick sinus syndrome. Am Heart J 92:648-660, 1976 93. Seinfeld D, Altschuler H, Yipintsoi T, et al: Pathogenetic locus of the sick sinus syndrome. Clin Res 26:270A, 1978 94. Jordan JL, Yamaguchi I, Mandel WJ: Studies on the mechanism of sinus node dysfunction in the sick sinus syndrome. Circulation 57:217-222, 1978 95. Mandel W, Hayakawa H, Danzig R, et al: Evaluation of sinoatrial node function in man by overdrive suppression. Circulation 44:59-66, 1971 96. Mandel WJ, Laks MM, Orayashi K: Sinus node function. Evaluation in patients with and without sinus node disease. Arch Intern Med 135:388-394, 1975 97. Lassers BW: First year follow-up after recovery from acute myocardial infarction with complete heart block. Lancet 2: I 172, 1969 98. Strauss HC, Bigger JT Jr, Saroff AL, et al: Electrophysiologic evaluation of sinus node function in patients with sinus node dysfunction. Circulation 53:763, 1976 99. Engel TR, Bond RC, Schaal SF: First-degree sinoatria1 heart block: Sinoatrial block in the sick-sinus syndrome. Am Heart J 3: 303-3 10, I976 100. Dhingra RC, Amat-Y-Leon F, Wyndham C, et al: Clinical significance of prolonged sinoatrial conduction time. Circulation 55:8-15, 1977 101. Kulbertus HE, De Leval-Rutten D, Mary L, et al: Sinus node recovery time in the elderly. Br Heart J 37:420425, 1975 102. Breithardt G, Seipel L, Loogen F: Sinus node recovery time and calculated sinoatrial conduction time in normal subjects and patients with sinus node dysfunction. Circulation 56:43-50, 1977 103. Gupta PK. Lichstein F, Chada KD, et al: Appraisal of sinus nodal recovery time in patients with sick sinus syndrome. Am J Cardiol 34:265-270, 1974 104. Crook B, Kitson D, McComish M, et al: Indirect measurement of sinoatrial conduction time in patients with
JOHN
D. FISHER
sinoatrial disease and in controls. Br Hear& J 39:771-777, 1977 105. Fisher JD, Seinfeld D: Sinus node recovery times and sino atrial conduction times in subjects with and without sick sinus syndrome. Unpublished data 106. Josephson ME, Seides SF: Sinus Node Function. Clinical Cardiac Electrophysiology: Techniques and Interpretations. Philadelphia, Lea & Febiger, 1979, pp 6 l-78 107. Altschuler H, Fisher JC: Increasing the yield of the sinus recovery time in the sick sinus syndrome. Clin Res 24:205A, 1976 108. Benditt DG, Strauss HC, Scheinman MM, et al: Analysis of secondary pauses following termination of rapid atrial pacing in man. Circulation 54:436-441, 1976 109. Miller HC, Strauss HC: Measurement of sinoatrial conduction time by premature atria1 stimulation in the rabbit. Circ Res 35:935-947, 1974 110. Nishi K, Yoshikawa Y, Tokenaka F, et al: Electrical activity of sinoatrial node cells of the rabbit surviving a long exposure to cold Tyrode’s solution. Circ Res 41:242-247, 1977 I1 1. Cramer M, Hariman RJ, Boxer R, et al: Electrograms from the canine sinoatrial pacemaker recorded in vitro and in situ. Am J Cardiol42:939-946, 1978 112. Mackintosh AF, English MJ, Vincent R, et al: Low voltage electrical activity preceding right atrial depolarisation in man. Br Heart J 42:117-123, 1979 113. Breithardt G, Seipel L: Effect of premature atrial depolarizations on sinus node automaticity in man. Circulation 53:92%925, 1976 114. Steinbeck G, Luderitz B: Sinoatrial pacemaker shift following atrial stimulation in man. Circulation 56:402-409, 1977 I1 5. Narula OS, Shantha N, Vasquez M, et al: A new method for measurement of sinoatrial conduction time. Circulation 58:706-714, 1978 116. Breithardt G, Seipel L: Comparative study of two methods of estimating sinoatrial conduction time in man. Am J Cardiol42:965-972, 1978 117. Dhingra RC, Wyndham C, Amat-Y-Leon F, et al: Sinus nodal responses to atrial extrastimuli in patients without apparent sinus node disease. Am J Cardiol 36:445452, 1975 118. Billette J, Bonin JP: Acute ischemic sinus node dysfunctions in dogs. Pace 1:313,326, 1978 119. Parameswaran R, Ohe T, Goldberg H: Sinus node dysfunction in acute myocardial infarction. Br Heart J 38:93-96.1976 120. Altschuler H, Seinfeld D, Fisher JD: Unpredictability of site of conduction injury due to acute myocardial infarction. Circulation 55-56 (Suppl III): 220, 1977 (abstr) 121. Jordan J, Yamaguchi I, Mandel WJ: Characteristics of sinoatrial conduction in patients with coronary artery disease. Circulation 55:569--574, 1977 122. Brown KA, Maloney JD, Smith HC, et al: Carotid sinus reflex in pts undergoing coronary angiography: Correlation of degree and location of CAD with response to CSM. Circulation 62:697-703, 1980 123. Dhingra RC, Amat-Y-Leon F, Wyndham C, et al: Electrophysiologic effects of atropine on sinus node and
ELECTROPHYSIOLOGIC
atrium
in patients
81
TESTING
with sinus node dysfunction.
Am J Cardiol
38:848-855,1976
124. Reiffei JA, Bigger JT Jr, Giardina EGV: “Paradoxical” prolongation of sinus nodal recovery time after atropine in the sick sinus syndrome. Am J Cardiol 36:98-104, 1975 125. Dhingra RC, Deedwania PC, Cummings JM, et al: Electrophysiologic effects of lidocaine on sinus node and atrium in patients with and without sinoatrial dysfunction. Circulation 57:448-453, 1978 126. Seinfeld D, Altschuler H, Yipintsoi T, et al: Increasing the sensitivity of the sinus recovery time in the sick sinus syndrome. Clin Res 26:270A, 1978 127. Gann D, Tolentino A, Samet P: Electrophysiologic evaluation of elderly patients with sinus bradycardia. Ann Intern Med 90:24-29, 1979 128. Evans TR, Callowhill EA, Krikler DM: Clinical value of tests of sino-atrial function. Pace l:2-7, 1978 129. Josephson ME, Scharf DL, Kastor JA, et al: Atrial endocardial activation in man: Electrode catheter technique for endocardial mapping. Am J Cardiol 39:972-981, 1977 130. Josephson ME, Scharf DL, Kastor JA, et al: Atrial endocardial activation in man: Electrode catheter technique for endocardial mapping. Am J Cardiol 39:972-98 I, 1977 131. Masuda SMO, De Carvalho AP: Sinoatrial transmission and atrial invasion during normal rhythm in the rabbit heart. Circ Res 37:414421, 1975 132. James TN: The connecting pathways between the sinus node and AV node and between the right and left atrium in the human heart. Am Heart J 66:498-508, 1963 133. Sherf L: The atrial conduction system: Clinical implications. Am J Cardiol37:8 I448 17, 1976 134. Ross AM, Proper MC, Aronson AL: Sinoventricular conduction in atrial standstill. J Electrocardiol9:161, 1976 135. Waldo AL, MaClean WAH, Karp RB, et al: Sequence of retrograde atrial activation of the human heart: Correlation with P wave polarity. Br Heart J 39:634-640, 1977 136. Aranda J, Castellanos A, Moleiro F, et al: Effects of the pacing site on A-H conduction and refractoriness in patients with short P-R intervals. Circulation 53:33-39, 1976 137. Amato JJ, Khan A, Payne D, et al: Pacemaker implantation in infants and children, in Meere C (ed): Proceedings of the Sixth World Symposium on Cardiac Pacing. Montreal, Pacesymp 1979 138. Batsford WP, Akhtar M, Caracta A, et al: Effect of atria1 stimulation site on the electrophysiological properties of the atrioventricular node in man. Circulation 50:283-292, 1974 139. Anderson RH, Becker AE. Wenink ACG, et al: The development of the cardiac specialized tissue, in Wellens HJJ, Lie KI, Janse MJ (eds): The Conduction System of the Heart: Structure, Function and Clinical Implications. Philadelphia, Lea & Febiger, 1976 140. Gelband H, Bush H, Rosen M, et al: Electrophysiologic properties of isolated preparations of human atria1 myocardium. Circ Res 30:293. 1972 141. Hordof AJ, Edie R, Malm JR, et al: Electrophysiologic properties and response to pharmacologic agents of fibers from diseased human atria. Circulation 54:774-779, 1976 142. Giusti RP, Fisher JD: Prolongation of intra-atrial
conduction time in response to atrial pacing. Clin Res 24:218A, 1976 143. Millar RNS, Mauer BJ, Rei DS, et al: Studies of intra-atrial conduction with bipolar atrial and His electrograms. Br Heart J 35:604-609, I973 144. Waldo Al, Bush HL, Gelband H, et al: Effects canine F Wave of discrete lesions in the specialized tracts, Circ Res 29:452, 1971
on the atrial
145. Scherlag BJ, Yeh BK, Robinson MJ: Inferior atrial pathway in the dog. Circ Res 31:18, 1972
inter-
146. Leier CV, Jewel1 GM, Magorien RD, et al: Interatrial conduction (activation) times. Am J Cardiol 44:442446.1979 147. Fishman D, Moran JF, Randall W, et al: Effect of left sympathetics on AV nodal conduction properties. Clin Res 25:22lA, 1977 148. Hageman CR, Goldberg JM, Armour JA, et al: Cardiac dysrhythmias induced by autonomic nerve stimulation. Am J Cardiol 32:823-830, 1973 149. Brodsky M, Wu D, Denes P, et al: Arrhythmias documented by 24-hour continuous ECG monitoring in 50 male medical students without apparent heart disease. Am J Cardiol 39:390-395, 1977
150. Meytes 1, Kaplinsky E, Yakini JH, et al: Wenckebath AV block: A frequent feature following heavy physical training. Am Heart J 90:426-430, 1975 I5 1. Young D, Eisenberg RE, Fish B, et al: Wenckebach AV block (Mobitz type 1) in children and adolescents. Am J Cardiol40:383-388, 1977 152. Janse MJ, Van Capelle FJL, Anderson RH, et al: Electrophysiology and structure of the atrioventricular node of the isolated rabbit heart, in Wellens HJJ, Lie KI, Janse MJ: The Conduction System of the Heart: Structure, Function and Clinical Implications. Philadelphia, Lea & Febiger, 1976 153. Pahlajani DB, Muller RA, Serratto M: Patterns of AV conduction in children. Am Heart J 90:165-171, 1975 1.54. Billette J, Bonin JP: Rate-induced shortenings in refractory periods and conduction time in the dog atrioventricular node. in Meere C (ed): Proceedings of the Vlth World Symposium on Cardiac Pacing, Pace Symp, Montreal. 1979, chap 1 l-4 155. Bharato S, Dhingra RC, Lev M, et al: Conduction system in a patient with Prinzmetals’ angina and transient AV block. Am J Cardiol 39:120-125, 1977 156. Anderson RH, Wenick ACG, Losekoot TG, et al: Congenitally complete heart block. Developmental aspects. Circulation 56:90-101, 1977 157. Narula man: Response parasympathetic
OS, Narula JT: Junctional pacemakers in to overdrive suppression with and without blockade. Circulation 57:88&889, 1978
158. Dhingra RC, Wyndham C, Amat-Y-Leon F, et al: Significance of A-H interval in patients with chronic bundle branch block: Clinical, electrophysiologic and follow-up observations. Am J Cardiol 37:231-236, 1976 159. Dhingra RC, Wyndham C. Bauernfeind R, et al: Significance of block distal to the His bundle induced by atrial pacing in patients with chronic bifascicular block. Circulation 60:1455-1465, 1979 160. Castillo
C, Castellanos
A Jr: Retrograde
activation
82
of the His bundle in the human heart. Am J Cardiol 27:264-271,197l 161. Josephson ME, Kastor JA: His-Purkinje conduction during retrograde stress. J Clin Invest 61:171-177, 1978 162. Akbtar M, Gilbert Cj, Wolf FG, et al: Retrograde conduction in the His-Purkinje system: Analysis of the routes of impulse propagation using His and right bundle branch recordings. Circulation 59:1252-1265, 1979 163. Josephson ME, Caracta AR, Ricciutti MA, et al: Electrrophysidogic properties of procainamide in man. Am J Cardiol 33596-603, 1974 164. Cannom DS: The effects of procaine amide in left bundle branch block. Circulation 51-52 (Suppl II):137, 1975 165. McKenna WJ, Rowland E, Davies J, et al: Failure to predict development of atrioventricular bloc with electrophysiological testing supplemented by ajmaline. Pace 3:666669,198O 166. Gupta PK, Lichstein E, Chauda KD: Lidocaineinduced heart block in patients with bundle branch block. Am J Cardiol 33:487-492, 1974 167. Narula OS, Samet P: Predilection of elderly females for intra-His bundle (BH) blocks. Circulation 49-50 (Suppl 111):395, 1974 168. Narula OS, Samet P: Wenckebach and Mobitz type II A-V block due to block within the His bundle and bundle branches. Circulation 4 I :947-965, 1970 169. Gupta PK, Lichstein E, Chada KD: Chronic His bundle block: Clinical, electrocardiographic, electrophysiological, and follow-up studies on 16 patients. Br Heart J 38:1343-1349,1976 170. Bharatii S, Lev M, Wu D, et al: Patbophysiologic correlations in two cases of split His bundle potentials. Circulation 49:615-623, 1974 17 1. Nasrallah AT, Gillette PC, Mullins CE: Congenital and surgical atrioventricular block within the His bundle. Am J Cardiol 36:9 14-920, 1975 172. McAnulty JH, Murphy E, Rohimtoola SH: A prospective evaluation of intrahisian conduction delay. Circulation 59:1035-1039, 1979 173. Dhingra RC, Denes P, Wu D, et al: Prospective observations in patients with chronic bundle branch block and marked H-V prolongation. Circulation 53:600-604, 1976 174. Rosen KM, Dhingra RC, Wyndham CRC, et al: Significance of HV interval in 515 patients with chronic bifascicular block. Am J Cardiol45:405, 1980 175. Narula OS: Intraventricular conduction defects: Current concepts and clinical significance, in Narula OS (ed): Cardiac Arrhythmias: Electrophysiology, Diagnosis and Management. Baltimore, Williams & Wilkins, 1979, p 114 176. Denes P, Dhingra RC, Wu D: H-V interval in patients with bifascicular block (right bundle branch block and left anterior hemiblock). Clinical, electrocardiographic, and electrophysiologic correlation. Am J Cardiol 35:23-29, 1975 177. Scheinman MM, Peters RW, Brennan M, et al: Prognostic value of infranodal conduction time in patients with chronic bundle branch block. Circulation 56:240-245, 1977 178. Denes P, Dhingra RC, Wu D, et al: Sudden death in
JOHN
D. FISHER
patients with chronic bifascicular block, Arch Intern Med 137:1005-1010,1977 179. Gupta PK, Licbstein E, Chadda KD: Fol!ow-up studies in patients with right bundle branch block and left anterior hemiblock: Significance of H-V interval. J Electrocardiol lO:221-224, 1977 180. McAnulty JH, Rahimitcola SH, Murphy ES, et al: A prospective study of sudden death in “high-risk” bundlebranch block. N Engl J Med 299:209-215, 1978 181. Dhingra RC, Wyndham C, Amat-Y-Leon F, et al: Incidence and site of atrioventricular block in patients with chronic bifascicular block. Circulation 59:238-246, 1979 182. Peters RW, Scheinman MM, Modin G, et al: Prophylactic permanent pacemakers for patients with chronic bundle branch block. Am J Med 66:978-985, 1979 183. Scbeinman M, Weiss A, Kunkel F: His bundle recordings in patients with bundle branch block and transient neurologic symptoms. Circulation 48:322-330, 1973 184. Vera Z, Mason DT, Fletcher RD, et al: Prolonged His-Q interval in chronic bifascicular block. Relation to impending complete heart block. Circulation 53:46, 1976 185. Altschuler H, Fisher JD, Furman S: Significance of isolated H-V interval prolongation in symptomatic patients without documented heart block. Am Heart J 97:19, 1979 186. Surawicz B: Prognosis of patients with chronic bifascicular block (editorial and review). Circulation 60:4&42, 1979 187. Dhingra RC, Wyndham C, Bauernfeind R, et al: Significance of chronic bifascicular block without apparent organic heart disease. Circulation 60:33-39, 1979 188. Kulbertus HE, De Leval-Rutten F, Dubois M, et al: Prognostic significance of left anterior bemiblock with right bundle branch block in mass screening. Am J Cardiol 41:385, 1978 (abstr) 189. McAnulty JH, Kauffman, S, Murphy E: Survival in patients with intraventricular conduction defects. Arch Intern Med 138:30-35, 1978 190. Dhingra RC, Amat-Y-Leon F, Wyndham C, et al: Significance of left axis deviation in patients with chronic left bundle branch block. Am J Cardiol42:551-556, 1978 191. Narula OS, Samet P: Right bundle branch block with normal, left or right axis deviation: Analysis by His bundle recordings. Am J Med 51:432455, 1971 192. Levites R, Haft JL: Significance of first degree heart block (prolonged PR interval) in bifascicular block. Am J Cardiol34:259-264, 1974 193. Castellanos A Jr: Letters to the editor: H-V intervals in LBBB. Circulation 47: I1 33-1134, 1973 194. Rosen KM: H-V intervals in LBBB. Circulation 47:1134, 1973 195. Wu D, Denes P, Dhingra R, et al: Bundle branch block: Demonstration of the incomplete nature of some “complete” bundle branch and fascicular blocks by the extrastimulus technique. Am J Cardiol 33:583-589, 1974 196. Lichstein E, Mahapatra R, Gupta PK, et al: Significance of complete left bundle branch block with left axis deviation. Am J Cardiol44:239-242, 1979 197. Tans AC, Lie KI, Durrer D: Clinical setting and prognostic significance of high degree atrioventricular block in acute inferior myocardial infarction: A study of 144 patients. Am Heart J 99:4-8, 1980 198. Biddle TL, Ehrich DA, Yu PN, et al: Relation of
ELECTROPHYSlOLOGlC
TESTING
heart block and left ventricular dysfunction in acute myocardial infarction. Am J Cardiol 39:961-966, 1977 199. Jones ME, Terry G, Kenmure ACF: Frequency and significance of conduction defects in acute myocardial infarction. Am Heart J 94:163-167, 1977 200. Ginks WR, Sutton R, Oh W, et al: Long-term prognosis after acute anterior infarction wth atrioventricular block. Br Heart J 39: 186-l 89, 1977 201. Hindham MC, Wagner GS, Jaro M: The clinical significance of bundle branch block complicating acute myocardial infarction. I. Clinical characteristics, hospital mortality, and one-year follow-up. Circulation 58:679-688, 1978 202. Hindham MC, Wagner GS, Jaro M: The clinical significance of bundle branch block complicating acute myocardial infarction. II. Indications for temporary and permanent pacemaker insertion. Circulation 58:.689-699, 1978 203. Godman MJ, Lassers BW, Julian DC: Complete bundle-branch block complicating acute myocardial infarction. N Engl J Med 282:237-240, 1970 204. Nimetz AA, Shubrooks SJ Jr, Hutter AM, et al: The significance of bundle branch block during acute myocardial infarction. Am Heart J 90:439-444, 1975 205. Waters DD, Mizgala HF: Long-term prognosis of patients with incomplete bilateral bundle branch block complicating acute myocardial infarction. Role of cardiac pacing, Am .I Cardiol 34: l-5, I974 206. Ritter WS, Atkins JM, Blumquist CG, et al: Permanent pacing in patients wtih transient trifascicular block during acute myocardial infarction. Am J Cardiol 38:205208, 1976 207. Norris RM, Croxson MS: Bundle branch block in acute myocardial infarction. Am Heart J 79:728-733, 1970 208. Scheinman M, Brenman B: Clinical and anatomic implications of intraventricular conduction blocks in acute myocardial infarction. Circulation 46:753-760, 1972 209. Lichstein E, Gupta PK, Chadda KD: Long-term survival of patients with incomplete bundle-branch block complicating acute myocardial infarction. Br Heart J 83:924-930, 1975 210. Lie KI, Wellens HJ, Schuilenburg RM, et al: Factors influencing prognosis of bundle branch block complicating acute antero-septal infarction. The value of His bundle recordings. Circulation 50:935-941, 1974 21 I. Gould L, Reddy CVR, Kim SG, et al: His bundle electrogram in patients with acute myocardial infarction. Pace 2:428-434, 1979 212. Harper R, Hudt D, Vohra J, et al: His bundle electrogram in patients with acute myocardial infarction complicated by atrioventricular or intraventricular conduction disturbances. Br Heart J 37:705-710, 1975 213. Buyukozturk K, Korkut F, Merit M, et al: Prognostic significance of isolated left anterior hemiblock and left axis deviation in the course of acute myocardial infarction. Br Heart J 39:1192-l 195, 1977 214. Rosenbaum MB, Yesuron J, Lazzari JO, et al: Left anterior hemiblock obscuring the diagnosis of right bundle branch block. Circulation 48:298-303, 1973 215. Sclarouskys S, Lewin RF, Strasberg B, et al: Left anterior hemiblock obscuring the diagnosis of right bundle
83 branch block in acute myocardial infarction. Circulation 60:26-32.1979 216. Fisher ML, Mugmon MA, Carliner NH, et al: Left anterior fascicular block: Electrocardiographic criteria for its recognition in the presence of inferior myocardial infarction. Am J Cardiol44:645-650, 1979 217. Rosen KM, Loeb HS, Chuquimia R, et al: Site of heart block in acute myocardial infarction. Circulation 42:925-933, 1970 218. Altschuler H, Seinfeld D, Fisher JD: Unpredictability of site of conduction injury due to acute myocardial infarction. Circulation 55-56(Suppl III): 220, 1977 (abstr) 219. Sinker D, Parameswaran R, Goldberg H: Sinus and A-V nodal dysfunction following myocardial infarction. J Electrocardiology 8:281-283, 1975 220. Nasrallah AT, Beard EF: Intra-His bundle block complicating acute inferior myocardial infarction. Chest 69:420-422,1976 221. Kosowsky BD, Latif P, Radoff AM: Multilevel 8‘trioventricular block. Circulation 54:914-921, 1976 222. Friedman HS, Zaman Q, Haft Jf, et al: Assessment of A-V conduction in aortic valve disease. Am J Cardiol 39:314, 1977 (abstr) 223. Dhingra RC, Amat-Y-Leon F, Pietras RJ, et al: Sites of conduction disease in aortic stenosis. Significance of valve gradient and calcification. Ann Intern Med 87:275280, 1977 224. Ritchie JL, Hammermeister KE, Kennedy JW: Refractory ventricular tachycardia and fibrillation in a patient with the prolapsing mitral leaflet syndrome: Successful control with overdrive facing. Am J Cardiol 37:314-316, 1976 225. Wei JY, Bulkley BH, Schaeffer AH, et al: Mitralvalve prolapse syndrome and recurrent ventricular tachyarrhythmias: A malignant variant refractory to conventional drug therapy. Ann Intern Med 89:6-9, 1978 226. Cosio FG, Moro C, Alonso M, et al: The Q waves of hypertrophic cardiomyopathy. An electrophysiologic study. N Engl J Med 302:96-99, 1980 227. Johnson AD, Daily PO: Hypertrophic subaortic stenosis complicated by high degree heart block: Successful treatment with an atrial synchronous ventricular pacemaker. Chest 671491-494, 1975 228. Probst P, Pachinger 0, Murad AA, et al: The HQ time in congestive cardiomyopathies. Ani Heart J 97:436441,1979 229. Luca C: Electrophysiological properties of right heart and atrioventricular conducting system in patients with alcoholic cardiomyopathy. Br Heart J 42:274-28 I, 1979 230. Bharati S, Lev M, Denes P: Infiltrative cardiomyopathy with conduction disease and ventricular arrhythmia: Electrophysiologic and pathologic correlations. J Cardiol 45:163%173, 1980 23 1. Vigorita VJ, Hutchins GM: Cardiac conduction system in hemochromatosis: Clinical and pathologic features of six patients. Am J Cardiol44:418-423, 1979 232. Wray R, Iveson M: Complete heart block and systemic lupus erythematosus. Br Heart J 37:982-983, 1975 233. McCue CM, Mantakas ME, Tingelstad JB, et al: Congenital heart block in newborns of mothers with connective tissue disease. Circulation 56:82-90, 1977 234. Winkler RB, Nora AH, Nora JJ: Familial congeni-
a4 tal complete heart block and maternal systemic lupus erythematosis. Circulation 56: 1 103-l 107, 1977 235. Fiddler GI, Campbell RWF, Pottage A, et al: Varicella myocarditis presenting with unusual ventricular arrhythmias. Br Heart J 39: I 150-I 153, 1977 236. Gann D, Narula OS, Kaplan S, et al: Complete heart block with gonococcal septicemia. Ann Intern Med 86:749750, 1977 237. Hernandez-Pieretti 0, Morales-Rocha J, Acquatella H, et al: Pacemaker inplantation in chronic Chagas’ heart disease complicated by Adams-Stokes Syndrome. Am J Cardiol46:114-I 17, 196.5 238. Rosenbaum MB, Alvarez AJ: The electrocardiogram in chronic chagesic myocarditis. Am Heart J 50:492, 1955 239. Wei JY, Genecin A, Greene HL, et al: Coronary spasm with ventricular fibrillation during thyrotoxicosis: Response to attaining euthyroid state. Am J Cardiol43:335339,1979 240. Gavrilescu S, Luca C, Streian C, et al: Monophasic action potentials of right atrium and electrophysiological properties of AV conducting system in patients with hypothyroidism. Br Heart J 38:135&1354, 1976 241. Greenspan AM, Camardo JS, Horowitz LN, et al: Strength-interval relations in human ventricle. Circulation 59-60 (Suppl II): 23, 1979 (abstr) 242. Denes P, Wu D, Dhingra R, et al: The effects of cycle length on cardiac refractory periods in man. Circulation 49:3241, 1974 243. Dubrow IW, Fisher EA, Amat-Y-Leon F, et al: Comparison of cardiac refractory periods in children and adults. Circulation 51:485491, 1975 244. Watanabe Y, Nishimura M: Terminology and electrophysiologic concepts in cardiac arrhythmias. V. Phase 3 block and phase 4 block. Part I. Pace 2:335, 1979 245. Watanabe Y, Nishimura M: Terminology and electrophysiologic concepts in cardiac arrhythmias. VI. Phase 3 block and phase 4 block. Part 2. Pace 2:624, 1979 246. El-Sherif N, Scherlag BJ, Lazarra R, et al: Pathophysiology of tachycardiaand bradycardia-dependent block in the canine proximal His-Purkinje system after acute myocardial ischemia. Am J Cardiol 33:540, 1974 247. Castellanos A, Khuddus SA, Sommer LS, et al: His bundle recordings in bradycardia-dependent AV block induced by premature beats. Br Heart J 37:570-575, 1975 248. Asha AS, Castellanos A Jr, Wells D, et al: Type I, type II, and type III gaps in bundle-branch conduction. Circulation 47:325-330, 1973 249. Wu D, Denes P, Dhingra R, et al: Nature of the gap phenomenon in man. Circ Res 34:682-692, 1974 250. Akhtar M, Damato AN, Batsford WP, et al: Unmasking and conversion of gap phenomenon in the human heart. Circulation 49:624-630, 1974 25 I. Akhtar M, Damato AN, Caracta AR, et al: The gap phenomena during retrograde conduction in man. Circulation 4981 l-817, 1974 252. Akhtar M, Caracta AR, Lau SH, et al: Demonstration of intra-atrial conduction delay, block, gap and reentry: A report of two cases. Circulation 58:947-955, 1978 253. Waleffe A, Bruninx P, Demoulin J-C, et al: Two unusual cases of intra-atrial gap. Br Heart J 39:451-455, 1977
JOHN
D. FISHER
254. Puech P, Guimond C, Nadeau R, et al: Supernormal conduction in the intact heart; in Narula OS (ed): Cardiac arrhythmias: Electrophysiology, Diagnosis and Management. Baltimore, Williams & Wilkins, 1979, pp 40-56 255. Childers RW: Supernormality, in: Complex Electrocardiography I. Philadelphia, FA Davis, 1973, pp 136-l 58 256. Cranefield PF, Wit AL, Hoffman BF: Genesis of cardiac arrhythmias. Circulation 47:190, 1973 257. Rosen MR, Danilo P Jr: The electrophysiological basis for cardiac arrhythmias, in Narula OS (ed): Cardiac Arrhythmias: Electrophysiology, Diagnosis and Management. Baltimore, Williams & Wilkins, 1979, pp 3-13 258. Vassalle M, Cummins M, Castro C, et al: The relationship between overdrive suppression and overdrive excitation in ventricular pacemakers in dogs. Circ Res 38367, 1976 259. Vassale M: The relationship among natural cardiac pacemakers. Overdrive suppression. Circ Res 41:269-277, 1977 260. Wit AL, Cranefield PF: Triggered activity in cardiac muscle fibers of the simian mitral valve. Circ Res 38:85-98, 1976 26 I. Watanabe Y: Terminology and electrophysiologic concepts in cardiac arrhythmias. III. Exit block, entrance block and protection block. Pace 1:498-509, 1978 262. Schamroth L: The pathogenesis and mechanism of ventricular arrhythmias, in Yu PN, Goodwin JF (eds): Progress in Cardiology, 3. Philadelphia, Lea & Febiger, 1974, p 75 263. Kupersmith J: Electrophysiologic mapping during open heart surgery. Prog Cardiovasc Dis 19: 167, 1976 264. Spielman SR, Michelson EL, Horowitz LN, et al: The limitations of epicardial mapping as a guide to the surgical therapy of ventricular tachycardia. Circulation 56:666-670,197s 265. Ideker RE, Smith WM, Wallace AG: A computerized method for the rapid display of ventricular activation during the intraoperative study of arrhythmias. Circulation 59:449%458,1979 266. Josephson ME, Horowitz LN, Farshidi A, et al: Recurrent sustained ventricular tachycardia. 2. Endocardial mapping. Circulation 57:440-447, 1978 267. Curry PVL, O’Keefe DB, Pitches D, et al: Localisation of ventricular tachycardia by a new technique: Pacemapping. Circulation 59-60 (Suppl II): 25, 1979 268. Josephson ME: Paroxysmal supraventricular tachycardia: An electrophysiologic approach. Am J Cardiol 41:1123-l 126, 1978 269. Narula OS: Sinus node re-entry. A mechanism for supraventricular tachycardia. Circulation 50:1114-l 128, 1974 270. Narula OS: Paroxysmal supraventricular tachycardia due to sinus node and intra-atrial reentry, in Narula OS (ed): Cardiac Arrhythmias: Electrophysiology, Diagnosis and Management. Baltimore Williams & Wilkins, 1979, pp 272-293 271. Wu D, Amat-Y-Leon F, Denes P, et al: Demonstration of sustained sinus and atrial re-entry as a mechanism of paroxysmal supraventricular tachycardia. Circulation 51:234-243, 1975 272. Bauernfeind RA, Amat-Y-Leon F, Dhingra RC, et
ELECTROPHYSIOLOGIC
85
TESTING
al: Chronic nonparoxysmal sinus tachycardia in otherwise healthy persons. Ann Intern Med 91:702-710, 1979 273. Tenczer J, Littmann L, Molnar F, et al: Atrial reentry in chronic repetitive supraventricular tachycardia. Am Heart J 99:349-353, 1980 274. Coumel P, Flammang D, Attuel P, et al: Sustained intra-atrial reentrant tachycardia. Electrophysiologic study of 20 cases. Clin Cardiol 2:167-178, 1979 275. Ogawa S, Dreifus LS, Osmick MJ: Longitudinal dissociation of Bachmann’s bundle as a mechanism of paroxysmal supraventricular tachycardia. Am J Cardiol 40:915922,1977 276. Maclean WAH, Karp RB, Kouchoukos NT, et al: P waves during ectopic atrial rhythms in man. A study utilizing atrial pacing with fixed electrodes. Circulation 52:426-434, 1975 277. Gillette PC, Garson A Jr: Electrophysiologic and pharmacologic characteristics of automatic ectopic atria1 tachycardia. Circulation 56:571-575, 1977 278. Goldreyer BN, Gallagher JJ, Damato AN: The electrophysiologic demonstration of atria1 ectopcic tachycardia in man. Am Heart J 85:205, 1973 279. Coumel P, Leclerq J-F, Attuel P: Automatic influences in the genesis of atria1 arrhythmias: Atrial flutter and fibrillation of vagal origin, in Narula OS (ed): Cardiac Arrhythmias: Electrophysiology, Diagnosis and management. Baltimore, Williams & Wilkins, 1979, pp 2433255 280. Waldo AL, Wells JL Jr, Plumb VJ, et al: Characterization of atrial flutter: Studies in patients following open heart surgery, in Narula OS (ed): Cardiac Arrhythmias: Electrophysiology, Diagnosis and Management. Baltimore, Williams & Wilkins, 1979, pp 256627 1 281. Waldo AL, Maclean WAH, Karp RB, et al: Entrainment and interruption of atrial flutter with atrial pacing: Studies in man following open heart surgery. Circulation 56:737-745, 1977 282. Denes P, Wu D, Amat-Y-Leon F, et nants of atrioventricular nodal re-entrance atrial stimulation in patients with dual A-V Circulation 56:253-259, 1977 283. Thapar MK, Gillette PC: Dual nodal pathways: A common electrophysiologic children. Circulation 60: 136991374, 1979
al: The determiwith premature nodal pathways. atrioventricular response
in
284. Josephson ME, Kastor JA: Paroxysmal supraventricular tachycardia: Is the atrium a necessary link? Circulation 54:430-435, 1976 285. Akhtar M, Damato AN, Batsford WP, et al: Induction of atrioventricular nodal reentrant tachycardia after atropine. Report of five cases. Am J Cardiol 36:286-291, 1975 286. Fabregas RA, Han J, Gael BG, et al: Facilitation of A-V nodal reciprocation by procainamide. Am Heart J 9 1:46&467, 1976 287. Sung RJ, Styperek JL, Myerburg RJ, et al: Initiation of two distinct forms of atrioventricular nodal reentrant tachycardia during programmed ventricular stimulation in man. Am J Cardiol 42:40&415, 1978 288. Wu D, Denes P, Amat-Y-Leon F, et al: An unusual variety of atrioventricular nodal re-entry due to retrograde dual atrioventricular nodal pathways. Circulation 56:50-59, I977
289. Wolff GS, Sung RJ, Pickoff A, et al: The fast-slow form of atrioventricular nodal reentrant tachycardia in childrenAmJCardiol43:1181-1188, 1979 290. Coumel P: Junctional reciprocating tachycardias. The permanent and paroxysmal forms of A-V nodal reciprocating tachycardias. J Electrocardiol 8:79-90, 1975 291. Coumel P, Attuel P, Leclerq LF: Permanent form of junctional reciprocating tachycardia: Mechanism, clinical and therapeutic implications, in Narula OS (ed): Cardiac Arrhythmias: Electrophysiology, Diagnosis and Management. Baltimore, Williams & Wilkins, 1979, pp 347-363 292. Csapo G: Paroxysmal nonreentrant tachycardias due to simultaneous conduction in dual atrioventricular nodal pathways. Am J Cardiol43:1033-1045, 1979 293. Garson A Jr, Gillette PC: Junctional ectopic tachycardia in children: Electrocardiography, electrophysiology and pharmacologic response. Am J Cardiol 44:298-302, 1979 294. Denes P, Kehoe R, Rosen KM: Multiple reentrant tachycardias due to retrograde conduction of dual atrioventricular bundles with atrioventricular nodal-like properties. Am J Cardiol44:162-170,1979 295. Ferrior MI: Preexcitation. Am J Med 62:715-729, 1977 296. Narula OS: Wolff-Parkinson White syndrome. A review. Circulation 47:872-887, 1973 297. Wolff GS, Han J, Curran J: Wolff-Parkinson-White syndrome in the neonate. Am J Cardiol41:559-563, 1978 298. Gillette PC, Garson A Jr, Kugler JD: Wolff-Parkinson-white syndrome in children: Electrophysiologic and pharmacologic characteristics. Circulation 60: 1487-1495, 1979 299. Gavrilescu S, Gavrilescu M, Luca C: Accelerated atrioventricular conduction during acute myocardial infarction. Am Heart J 94:21-27, 1977 300. Svenson RH, Miller HC, Gallagher JJ, et al: Electrophysiological evaluation of the Wolff-Parkinson-White syndrome. Circulation 52:552-562, 1975 301. Denes P, Wu D, Amat-Y-Leon F: Determinants of atrioventricular reentrant paroxysmal tachycardia in patients with Wolff-Parkinson-White syndrome. Circulation 58:415-425, 1978 302. Pritchett ELC, Gallagher JJ, Scheinman M, et al: Determinants of antegrade echo zone in the Wolff-Parkinson-white syndrome. Circulation 57:671-677, 1978 303. Sung RJ, Castellanos A, Mallon SM. et al: Mode of initiation of reciprocating tachycardia during programmed ventricular stimulation in the Wolff-Parkinson-White syndrome. Am J Cardiol40:24-31, 1977 304. Denes P, Wyndham CR, Amat-Y-Leon F, et al: Atrial pacing at multiple sites in the Wolff-Parkinson-White syndrome. Br Heart J 39:506-5 14, 1977 305. Tonkin AM, Miller HC, Svenson RH, et al: Refractory periods of the accessory pathway in the Wolff-Parkinson-white syndrome. Circulation 52:563-569, 1975 306. Gallagher JJ, Scaly WC, Kasell J, et al: Multiple accessory pathways in patients with preexcitation syndrome. Circulation 54:571, 1976 307. Narula OS: Retrograde pre-excitation. Comparison of antegrade and retrograde conduction intervals in man. Circulation 50:1129-l 143, 1974 308. Wellens HJJ, Durrer D: Patterns of Ventriculo-
86
atrial condnction in the Wolff-Parkinson-White syndrome. Circulation 49:22, 1974 309. Klein GJ, Prystowsky EN, Pritchett ELC, et al: Atypical patterns of retrograde conduction over accessory atriovenetricular pathways in the Wolff-Parkinson-White syndrome. Circulation 60: 1477-l 486, 1979 310. Zipes DP, De Joseph RL, Rothbaum DA: Unusual properties of accessory pathways. Circulation 49: 1200, 1974 3 11. Rosen KM: A-V nodal reentrance. An unexpected mechanism of paroxysmal tachycardia in a patient with preexcitation. Circulation 47: 1267-I 273, 1973 312. Spurrell RAJ, Krikler D, Sowton E: Two or more intra-AV nodal pathways in association with either a James or Kent extranodal bypass in 3 patients with paroxysmal supraventricular tachycardia. Br Heart J 35:113-122, 1973 313. Sung RJ, Styperek JL: Electrophysiologic identihcation of dual atrioventricular nodal pathway conduction in patients with reciprocating tachycardia using anomalous bypass tracts. Circulation 60:1464-1476, 1979 314. Przybylski J, Chiale PA, Halpern MS, et al: Existence of automaticity in anomalous bundle of Wolff-Parkinson-white syndrome. Br Heart J 40:672-680, 1978 315. James TN, Puech P: De subitaneis mortibus IX. Type A Wolf-Parkinson-White syndrome. Circulation 50:1264-1280.1974 316. Wellens HJ, Durrer D: Effect of digitalis on Atrioventricular conduction and circus-movement tachycardias in patients with Wolff-Parkinson-White syndrome. Circulation 47:1229-1233, 1973 317. Sellers DT, Bashore TM, Gallagher JJ: Digitalis in the pre-excitation syndrome: Analysis during atria1 fibrillation. Circulation 56:260-267, 1977 3 18. Dreifus LS, Wellens HJJ, Watanabe Y, et al: Sinus bradycardia and atrial fibrillation associated with WPW syndrome. Am J Cardiol 38: 149, 1976 319. Campbell RWF, Smith RA, Gallagher JJ, et al: Atrial fibrillation in the preexcitation syndrome. Am J Cardiol40:514-520, 1977 320. Klein GJ, Bashore TM, Sellers TD, et al: Ventricular fibrillation in the Wolff-Parkinson-White syndrome. N Engl J Med 301:108~1085,1979 321. Sung RJ, Castellanos A, Mallon SM: Mechanisms of spontaneous alternation between reciprocating tachycardia and atrial flutter-fibrillation in the Wolff-ParkinsonWhite syndrome. Circulation 56:409-416, 1977 322. Curry PVL: The hemodynamic and electrophysiological effects of paroxysmal tachycardia, in Narula OS (ed): Cardiac Arrhythmias: Electrophysiology, Diagnosis and Management. Baltimore, Williams & Wilkins, 1979, pp 364-38 I 323. Brechenmacher C: Atrio-His bundle tracts. Br Heart J 37:853-855, 1975 324. Benditt DC, Pritchett ELC, Smith WM, et al: Characteristics of atrioventricular conduction and the spectrum of arrhythmias in Lown-Ganong-Levine syndrome. Circulation 57:45&465, 1978 325. Josephson ME, Kastor JA: Supraventricular tachycardia in Lown-Ganong-Levine syndrome: Atrionodal versus intranodal reentry. Am J Cardiol40:521-527, 1977 326. Myerburg RJ, Sung RJ, Castellanos A: Ventricular
JOHN
D. FISHER
tachycardia and ventricular fibrillation in patients with short P-R intervals and narrow QRS complexes. Pace 2:568, 1979 327. Sung RJ, Gelband H, Castellanos A, et al: Clinical and electrophysiologic observations in patients with concealed accessory atrioventricular bypass tracts. Am J Cardiol40:839-847, 1977 328. Pritchett ELC, Gallagher JJ, Sealy WC, et al: Supraventricular tachycardia dependent upon accessory pathways in the absence of ventricular preexcitation. Am J Med 64:214-220, 1978 329. Ward DE, Camm AJ, Pearce RC: Incessant atrioventricular tachycardia involving an accessory pathway:Preoperative and intraoperative electrophysiologic studies and surgical correction. Am J Cardiol44:428-434, 1979 330. Orzan F, Gillette PC: Reciprocating tachycardia due to a right-sided unidirectional retrograde anomalous pathway (URAP). Pace 1:306-312,197s 331. Wu D, Denes P, Amat-Y-Leon F, et al: Clinical, electrocardiographic and electrophysiologic observations in patients with paroxysmal supraventricular tachycardia. Am J Cardiol 41:1045-1051, 1978 332. Farshidi A, Josephson ME, Horowitz LN: Electrophysiologic characteristics of concealed bypass tracts: Clinical and electrocardiographic correlates. Am J Cardiol 41:1052-1060, 1978 333. Spurrell RAJ, Krikler DM, Sowton E: Retrograde invasion of the bundle branches producing aberration of the QRS complex during SVT studied by programmed electrical stimulation. Circulation 50:487-495, 1974 334. Games JAC, Dhatt MS, Damato AN: Incidence, determinants and significance of fixed retrograde conduction in the region of the atrioventricular node. Am J Cardiol 44:1089-1098.1979 335. Spurrell RAJ, Krikler DM, Sowton E: Concealed bypasses of the atrioventricular node in patients with PCVT revealed by intracardiac electrical stimulation and verapamil. Am J Cardiol 33:590-595, 1974 336. Farre J, Ross D, Wiener I, et al: Reciprocal tachycardias using accessory pathways with long conduction times. Am J Cardiol44:1099-I 109, 1979 337. Tonkin AM: Management of arrhythmias due to accessory conduction pathways. Pace 1:482497, 1978 338. Rosen KM, Dhingra RC, Wyndham CRC: Editorial: Trading arrhythmia for atrioventricular block. Circulation 61:16-17, 1980 339. Ward DE, Camm AJ, Pearce RC:Incessant atrioventricular tachycardia involving an accessory pathway: Preoperative and intraoperative electrophysiologic studies and surgical correction. Am J Cardiol44:428-434, 1979 340. Wellens HJJ, Bar FW, Dassen WRM, et al: Effect of drugs in the Wolff-Parkinson-White syndrome. Importance of initial length of effective refractory period of the accessory pathway. Am J Cardiol46:665, 1980 341. Gallagher JJ, Sealy WC, Kasell J: Intraoperative mapping studies in the Wolff-Parkinson-White syndrome. Pace 2:523-537,1979 342. Wyndham C, Smith T, Arnsdorf M, et al: Successful surgical excision of paroxysmal atria1 tachycardia: In vivo and in vitro observations. Clin Res 27:442A, 1979 343. Klein GJ, Sealy WC, Pritchett ELC: Cryosurgical ablation of the atrioventricular node-His bundle: Long-term
ELECTROPHYSIOLOGIC
TESTING
follow-up and properties of the junctional pacemaker. Circulation 61:8-15, 1980 344. Gallagher JJ, Kasell J, Scaly WC, et al: Epicardial mapping in the Wolff-Parkinson-White syndrome. Circulation 57:854-866, 1978 345. Wyndham CR, Meeran MK, Smith T, et al: Epicardial activation of the intact human heart without conduction defect. Circulation 59:161-168, 1979 346. Sealy WC, Gallagher JJ: The surgical anatomy of Kent bundles based on electrophysiological mapping and surgical exploration. J Thorac Cardiovasc Surg 76:804-g 15, 1978 347. Gallagher JJ, Scaly WC, Kasell J, et al: Cryosurgical ablation of accessory atrioventricular connections: A method for correction of the pre-excitation syndrome. Circulation 55:471-479, 1977 348. Klein GJ, Harrison L, Ideker RD, et al: Reaction of the myocardium to cryosurgery: Electrophysiology and arrhythmogenic potential. Circulation 59:364-372, 1979 349. Fisher JD: Nonsurgical treatment of ventricular tachycardia: The value of serial provocative testing, in Narula OS (ed): Cardiac Arrhythmias: Electrophysiology, Diagnosis, and Management. Baltimore, Williams & Wilkins, 1979, pp 494-5 15 350. Waxman MB, Wald RW: Termination of ventricular tachycardia by an increase in cardiac vagal drive. Circulation 56:385-391, 1977 351. Waxman MB, Wald RW, Finley JP, et al: Valsalva termination of ventricular tachycardia. Circulation 62:843851,198O 352. Wellens HJJ, Bar FW, Lie KI: The value of the electrocardiogram in the differential diagnosis of a tachycardia with a widened QRS complex. Am J Med 64:27, 1978 353. Wit Al, Bigger JT Jr: Possible electrophysiological mechanisms for lethal arrhythmias accompanying myocardial ischemia and infarction. Circulation 51-52, (Suppl III):9661 15, 1975 354. El-Sherif N, Scherlag BJ, Lazzara R: Electrode catheter recordings during malignant ventricular arrhythmia following experimental acute myocardial ischemia. Circulation 51:1003-1014,1975 355. Kent KM, Smith ER, Redwood DR, et al: Electrical stability of acutely ischemic myocardium. Influences of heart rate and vagal stimulation. Circulation 47:291-298, 1973 356. Blatt CM, Verrier RL, Lown B: Acute blood pressure elevation and ventricular fibrillation threshold during coronary occlusion and reperfusion in the dog. Am J Cardiol 39:523-528, 1977 357. Penkoske PA, Sobel BE, Corr PB: Disparate electrophysiological alterations accompanying dysrhythmia due to coronary occlusion and reperfusion in the cat. Circulation 58:102331035, 1978 358. Murdock DK, Loeb JM, Euler DE, et al: Electrophysiology of coronary reperfusion. A mechanism for reperfusion arrhythmias. Circulation 61:175-l 82, 1980 359. Horowitz LN, Spear JF, Moore EN: Subendocardial origin of ventricular arrhythmias in 24-hour-old experimental myocardial infarction. Circulation 53:56-63, 1976 360. Spear JF, Michelson EL, Spielman SR, et al: The origin of ventricular arrhythmias 24 hours following experi-
87 mental anterior septal coronary artery occlusion. Circulation 55:844-852, 1977 361. El-Sherif N, Scherlag BJ, Lazzara R, et al: Reentrant ventricular arrhythmias in the late myocardial infarction period. I. Conduction characterictics in the infarction zone. Circulation 55:686-702, 1977 362. Myerburg RJ, Gelband H, Nilsson K, et al: Longterm electrophysiological abnormalities resulting from experimental myocardial infarction in cats. Circ Res 41:7384, 1977 363. Bailey JC, Anderson GJ, Pippenger D, et al: Reentry within the isolated canine bundle of His. Possible mechanism for reciprocal rhythm. Am J Cardiol 32:808-8 13, 1973 364. Akhtar M, Damato AN, Batsford WP, et al: Demonstration of re-entry within the His-Purkinje system in man. Circulation 50:115&l 162, 1974 365. Reddy CP, Khorasanchian A: Intraventricular reentry with narrow QRS complex. Circulation 61:641-647, 1980 366. Spureel RAJ, Sowton E, Deuchar DC: VT in 4 patients evaluated by programmed electrical stimulation of heart and treated in 2 patients by surgical division of anterior radiation of LBB. Br Heart J 35:1014-1025, 1973 367. Josephson ME, Horowitz LN, Farshidi A, et al: Sustained ventricular tachycardia: Evidence for protected localized reentry. Am J Cardiol42:416-424, 1978 368. Josephson ME, Horowitz LN, Farshidi A, et al: Recurrent sustained ventricular tachycardia. 1. Mechanisms. Circulation 57:43 1, 1978 369. Josephson ME, Horowitz LN, Farshidi A: Continuous local electrical activity. A mechanism of recurrent ventricular tachycardia. Circulation 57:659-665, 1978 370. Josephson ME, Horowitz LN, Farshidi A, et al: Recurrent sustained ventricular tachycardia. 4. Pleomorphism. Circulation. 59:459-468, 1979 371. Ross DL, Hamer AWF, Vohra JK, et al: Multiform ventricular tachycardia. Pace 3:24-37, 1980 372. Cohen SI, Deisseroth A, Hecht KS: Infra-His bundle origin of bidirectional tachycardia. Circulation 47: 12601266,1973 373. Zipes D: Electrophysiological mechanisms involved in ventricular fibrillation. Circulation 51 (Suppl III): 120, 1975 374. Spielman SR, Farshidi A, Horowitz LN, et al: Ventricular fibrillation during programmed ventricular stimulation: Incidence and clinical inplications. Am J Cardiol 42:913-918, 1978 375. Josephson ME, Spielman SR, Greenspan AM, et al: Mechanism of ventricular fibrillation in man. Observations based on electrode catheter recordings. Am J Cardiol 44:623-631, 1979 376. Engle WR, Moore EN, Spear JF, et al: The effect of multiple site pacing on ventricular fibrillation threshold. Am J Cardiol 39:274, 1977 (abstr) 377. Watson AB, Wright JS: A study of the vulnerability of the human heart to V fib during timed electrical stimulation of the T wave with pacemaker-like impulses, in Meere C (ed): Proc of the VIth World Symposium on Cardiac Pacing, Pace Symp, Montreal, 1979, pp l-6 378. Wellens HJJ, Duren DR, Lie KI: Observations on
88
mechanisms of ventricular tachycardia in man. Circulation 541237, 1976 379. Fisher JD, Cohen HL, Mehra R, et al: Cardiac pacing and pacemakers II. Serial electrophysiologic pharmacologic testing for control of recurrent tachyarrhythmias. Am Heart J 93:658-668, 1977 380. Fisher JD, Ostrow E, Mechra R, et al: Clinical correlations of ventricular vulnerability to electrophysiologic stresses, in Meere C (ed): Proc of the VIth World Symposium on Cardiac Pacing, Pace Symp, Montreal, 1979, pp l-5 38 1. Vandepol CJ, Farshidi A, Spielman SR, et al: Incidence and clinical significance of induced ventricular tachycardia. Am J Cardiol45:725-73 1, 1980 382. Horowitz LN, Josephson ME, Farshidi A, et al: Recurrent sustained ventricular tachycardia. 3. Role of the electrophysiologic study in selection of antiarrhythmic regimens. Circulation 58:986, 1978 383. Mason JW, Winkle RA: Electrode-catheter arrhythmia induction in the selection and assessment of antiarrhythmic drug therapy for recurrent ventricular tachycardia. Circulation 58:971-98.5, 1978 384. Fisher JD: Ventricular tachycardia-practical and provocative electrophysiology (editorial). Circulation 58:1000, 1978 385. Scheinman MM: Editorial: Induction of ventricular trachycardia: A promising new technique or clinical electrophysiology gone awry? Circulation 58:998-999, 1978 386. Josephson ME, Horowitz LN: Electrophysiologic approach to therapy of recurrent sustained ventricular tachycardia. Am J Cardiol43:631-642, 1979 387. Wellens HJJ: Value and limitations of programmed electrical stimulation of the heart in the study and treatment of tachycardias. Circulation 57:845, 1978 388. Lown B, Verrier RL, Blatt CM: Precordial mechanism stimulation for exposing electrical instability in the ischemic heart. Am J Cardiol42:425-428, 1978 389. Reddy CP, Gettes LS: Use of isoproterenol as an aid to electric induction of chronic recurrent ventricular tachycardia. Am J Cardiol44:705-713, 1979 390. Ruskin JN, Garan H: Chronic electrophysiologic testing in patients with recurrent sustained ventricular tachycardia. Am J Cardiol43:400, 1979 (abstr) 391. Greene HL, Reid TR, Schaeffer AH: The repetitive ventricular response in man: A predictor of sudden death. N Engl J Med 2991729. 1978 392. Schaeffer AH, Greene HL, Reid PR: Suppression of the repetitive ventricular response: an index of long-term antiarrhythmic effectiveness of aprindine for ventricular tachycardia in man. Am J Cardiol42:1007-1012, 1978 393. Fisher JD, Mehra R, Furman S: Termination of ventricular tachycardia with bursts of rapid ventricular pacing. Am J Cardiol 4 1:94-l 02, 1978 394. Fisher JD: Pacing for treatment of ventricular tachycardia, in Meere C (ed): Proceedings of the VIth World Symposium on Cardiac Pacing, Pace Symp, Montreal 1979, PP ‘-5 395. Fisher JD, Kim SC, Furman S: The role of implantable pacemakers in the control of recurrent ventricular tachycardia. Am J Cardiol (in press) 396. Horowitz LN, Horken AH, Kastor JA, et al:
JOHN
D. FISHER
Ventricular resection guided by epicardial and endocardial mapping for treatment of recurrent ventricular tachycardia. N Engl J Med 11:589-593,198O 397. Gallagher JJ, Cox JL: Editorial: Status of surgery for ventricular arrhythmias. Circulation 60:1440-1442, 1979 398. Guiraudon G, Fontaine G, Frank R: Encircling endocardial ventriculotomy: A new surgical treatment for life-threatening ventricular tachycardias resistant to medical treatment following MI. Ann Thorac Surg 26:438-444, 1978 399. Spurrell RAJ, Yates AK, Thorburn CW, et al: Surgical treatment of ventricular tachycardia following epicardial mapping studies. Br Heart J 37: 115, 1975 400. Fontaine G, Guiraudon G, et al: La Cartographie epicardique et le traitement chirurgical par simple ventriculotomie de certaines tachycardies ventriculaires rebelles par reentree. Arch Ma1 Coeur 68: 113, 1975 401. Gallagher JJ, Oldham HN, Wallace AG, et al: Ventricular aneurysm with ventricular tachycardia. Am J Cardiol 35~696, 1975 402. Gallagher JJ, Anderson RW, Kasell J, et al: Cryoablation of drug-resistant ventricular tachycardia in a patient with a variant of scleroderma. Circulation 57:190197,1977 403. Ricks WB, Winkle RA, Shumway NE, et al: Surgical management of life-threatening ventricular arrhythmias in patients with coronary artery disease. Circulation 56:3842,1977 404. Buda AJ, Stinson EB, Harrison DC: Surgery for life-threatening ventricular tachyarrhythmias. Am J Cardiol 44:1171-1177.1979 405. Thind GS, Blakemore WS, Zinsser HF: Ventricular aneurysmectomy for the treatment of recurrent ventricular tachyarrhythmia. Am J Cardiol 27:690-694, 1971 406. Basta LL, Tokeshita A, et al: Aneurysmectomy in treatment of ventricular and supraventricular tachyarrhythmias in patients with postinfarction and traumatic ventricular aneurysms. Am J Cardiol32:693, 1973 407. Wald RW, Waxman MB, Corey PN, et al: Management of intractable ventricular tachyarrhythmias after myocardial infarction. Am J Cardiol44:329-338, 1979 408. Lloyd R, Okada R, Stagg J, et al: The treatment of recurrent ventricular tachycardia with bilateral cervicothoracic sympathetic-ganglionectomy. Circulation 50:382, 1974 409. Zipes DP, Festoff B, Schaal SF, et al: Treatment of ventricular arrhythmias by permanent atrial pacemaker and cardiac sympathectomy. Ann Intern Med 68:591, 1968 410. Coyer BH, Pryor R, Kirsch WM, et al: Left stellectomy in the long QT syndrome. Chest 74:584-586, 1978 411. Wu D, Amat-Y-Leon F, Simpson RJ, et al: Electrophysiological studies with multiple drugs in patients with atriovntricular reentrant tachycardias utilizing an extranoda1 pathway. Circulation 56:727-736, 1977 412. Wu D, Wyndham CR, Denes P, et al: Chronic electrophysiologic study in patients with recurrent paroxysmal tachycardia, in Kulbertus HE (ed): A New Method for Developing Oral Antiarrhythmic Therapy. Baltimore, University Park, 1977, 294-3 11 413. Hartzler GO: Treatment of recurrent ventricular
ELECTROPHYSIOLOGIC
tachycardia by patient activated radio frequency ventricular stimulation. Mayo Clin Proc 54:75. 1979 414. Kehoe R, Bauernfeind RA, Wyndham CRC, et al: Inducible ventricular tachycardia in patients with out of hospital ventricular fibrillation. Am J Cardiol 45:444, 1980 (abstr) 415. Ruskin JN, Dimarco JP, Garan H: Electrophysiologic observations and selection of long-term antiarrhythmic therapy. New Engl J Med 303:607-613.1980 416. Mason JW, Winkle RA: Ability of induced ventricular tachycardia to predict long-term efficacy of antiarrhythmic drugs. New Engl J Med 303:1073-1077,198O 417. Horowitz LN, Josephson ME, Kastor JA: Intracardiac electrophysiologic studies as a method for the optimization of drug therapy in chronic ventricular arrhythmia. Prog in Cardiovasc Dis 23:8 l-98, 1980 418. Myerburg RJ, Conde CA, Sung RJ: Clinical, electrophysiologic and hemodynamic profile of patients resuscitated from prehospital cardiac arrest. Am J Med 68:568576,1980 419. Lie KI, Liem KL, Schuilenburg RM, et al: Early identification of patients developing late in-hospital ventricular fibrillation after discharge from the coronary care unit. Am J Cardiol41:674, I978 420. Lew HT. March HW: Control of recurrent ventricular fibrillation by transvenous pacing in the absence of heart block. Am Heart J 73~794-797, 1967 421. Haft JI: Treatment of arrhythmias by intracardiac electrical stimulation. Prog Cardiovasc Dis 16:539, 1974 422. Johnson RA, Hutter AM, De Sanctis RW, et al: Chronic overdrive pacing in the control of refractory ventricular arrhythmias. Ann Intern Med 80:380, 1974 423. Friedberg CK, Lyon LJ, Donoso E: Suppression of refractory recurrent ventricular tachycardia by transvenous rapid cardiac pacing and antiarrhythmic drugs. Am Heart J 79:44,
89
TESTING
1970
424. Moss AJ. Rivers RJ: Termination and inhibition of recurrent tachycardias by implanted pervenous pacemakers. Circulation 50:942, 1974 425. Cooper TB, Maclean WAH, Waldo AL: Overdrive pacing for supraventricular tachycardia: A Review of theoretical implications and therapeutic techniques. Pace 1:196221, 1978 426. Preston TA, Haynes RE, Gavin WA, et al: Permanent rapid atrial pacing to control supraventricular tachycardia. Pace 2:331, 1979 427. Waldo AL, Maclean WAH, Karp RB, et al: Continuous rapid atria1 pacing to control recurrent or sustained supraventricular tachycardias following open heart surgery. Circulation 54:245, 1976 428. Arbel ER, Cohen HC, Langendorf R, et al: Successful treatment of drug-resistant atrial tachycardia and intractable congestive heart failure with permanent coupled atrial pacing, Am J Cardiol41:336-340, 1978 429. Langendorf R, Pick A: Observations on the clinical use of paired electrical stimulation of the heart. Bull NY Acad Med 41:535, 1965 430. Bigger JT Jr, Jaffe CC: The effect of bretylium tosylate on the electrophysiologic properties of ventricular muscle and Purkinje fibers. Am J Cardiol 27:82-92, 1971 431. Krikler DM, Curry PVL, Buffet J: Dual-demand
pacing for reciprocating atrio-ventricular tachycardia. Br Med J 1:1114, 1976 432. Fisher JD, Furman S: Automatic termination of tachycardia by an implanted “upside down” demand pacemaker. Clin Res 26:231A, 1978 (abstr) 433. Dreifus LS, Berkovits BV, Kimibiris D, et al: Use of atria1 and bifocal cardiac pacemakers for treating resistant dysrhythmias. Eur J Cardio! 3:257, 1975 434. Sung RJ, Styperek JL, Castellanos A: Complete abolition of the reentrant SVI zone using a new modality of cardiac pacing with simultaneous atrioventricular stimulation. Am J Cardiol45:72-78, 1980 435. Akhtar M, Gilbert CJ, Al-Nouri M, et al: Electrophysiologic mechanisms for modification and abolition of atrioventricular junctional tach with simultaneous and sequential atrial and ventricular pacing. Circulation 60: 144331454, 1979 436. Spurrell RAJ, Sowton E: An implanted atrial synchronous pacemaker with a short atrioventricular delay for the prevention of paroxysmal supraventricular tachycardias. Electrocardiol 9:89, 1976 437. Critelli G, Grassi G, Chiariello M, et al: Automatic “scanning” by radiofrequency in the long-term electrical treatment of arrhythmias. Pace 2:289, 1979 438. Gurtner HP, Gertsch M, Zacouto F: Orthorhythmischer herzschrittmacher und salvenformige herzstimulation. Schweiz Med Wochenschr 105:33, 1975 439. Spurrell RAJ, Sowton E: Pacing techniques in the management of supraventricular tachycardias. J Electrocardiol 8:287, 1975 440. Escher DJW, Furman cardiac arrhythmias: Emphasis JAMA 217:2028,1970
S: Emergency treatment of on use of electrical pacing.
441. Hortzler GO: Treatment of recurrent ventricular tachycardia by patient activated radio frequency ventricular stimulation. Mayo Clin Proc 54:75, 1979 442. Goyal SL, Lichstein E, Gupta PK. et al: Refractory reentrant atrial tachycardia. Successful treatment with a permanent radio-frequency triggered atrial pacemaker. Am J Med 58:586.1975 443. Altamura G, Pistolese M, Boccadamo R: Atrial inhibited pacemaker with incorporated radiofrequency device used in the treatment of the brady-tachy syndrome, in Meere C (ed): Proc of the VI World Symposium on Cardiac Pacing, Pace Symp, Montreal. 1979, Chap 9-14 444. Kim SG, Fisher JD, Furman S, et al: Implantable ventricular burst pacemakers for termination of ventricular tachycardia, in Meere C (ed): Proc of the VI World Symposium on Cardiac Pacing, 1979, Pace Symp, Montreal. Chap 6-12 445. Neumann G, Funke H, Bakels N, et al: A new atrial demand pacemaker for the management of supraventricular tachycardias, in Meere C (ed): Proc of the VI World Symposium Cardiac Pacing, 1979, PaceSymp, Montreal, Chap 27-7 446. Furman S, Parsonnet V, Smyth N: Five-position pacemaker code (ICHD). Pace (in press) 447. Mirowski M, Mower MM, Langer A, et al: A chronically implanted system for automatic defibrillation in
90
active conscious dogs: Experimental model for treatment if sudden death from ventricular fibrillation. Circulation 58:90-94, 1978 448. Fisher JD. Ostrow E, Mehra R, et al: Clinical correlations of ventricular vulnerability to electrophysiologic stresses, in Meere C (ed): Proceedings of the VIth World Symposium on Cardiac Pacing, 1979, PaceSymp, Montreal. Chap 6-2 449. Brandenburg RO Jr, Holmes DR Jr, Hartzler Go: The electrophysiologic assessment of patients with syncope. Am J Cardiol (abstr) (in press)
JOHN
D. FISHER
450. Williams RS, Bashore TM: Proxysmal hypotension associated with sympathetic withdrawal. A new disorder of automatic vasomotor regulation. Circulation 62:901-908, 1980 45 1. Bigger JT Jr: A simple, rapid method for the diagnosis of first-degree sinoatrial block in man. Am Heart J 87:731-733, 1974 452. Engel TR, Schaal SF: Digitalis in the sick sinus syndrome: The effects of digitalis on sinoatrial automaticity and atrioventricular conduction. Circulation 48:1201-1207, 1973
Testing in the Diagnosis and With Known and Suspected and Tachycardias John D. Fisher
E
testing has LECTROPHYSIOLOGIC made possiblemore accurate diagnosisand treatment of recurrent tachycardias and syncopal episodes. The rapid expansion in clinical electrophysiology is reflected both in the number of reports in the literature and in the texts, monographs, and reviews appearing in recent years. ‘-* The challenge for the 1980swill be the continued refinement of present studies and the identification of high-risk patients for the development of bradycardias or tachycardias who warrant prophylactic treatment. Over the last decade, a battery of tests has been developed to assessthe electrophysiologic function of cardiac tissues.The details of these tests vary among investigators. Occasionally, differences in investigators’ assumptions,experience, or definitions may result in marked differences in viewpoints or conclusions, much to the consternation of the unwary reader. This article will review some of the electrophysiologic tests and procedures currently in use, their applications, and reliability.
Signal
When a wave front passesdirectly underneath the recording electrode it produces an “intrinsic deflection” on the electrogram that has highfrequency components. Depolarizations distant to the electrode give rise to lower frequency potentials at the recording site of a magnitude proportional to the tissue massundergoing excitation. When 40-500 Hz filters are used to measure far-field events, including ventricular depolarization during a His bundle study, the low-frequency potentials are lost, possibly giving an erroneoustiming for distant events. Catheterization
The surface electrocardiogram reflects *predominantly the sum of low-frequency highamplitude signals that reach the body surface from the working myocardium. The specialized conduction system generates low-amplitude potentials that do not reach the body surface well. Although some success has been reported in recording His bundle electrograms from the body surface using signal averaging techniques,9-‘2the technique is limited because the His bundle potential is submerged in the left atria1 depolarization unlessthere is a long P-R interval. Additionally, pacing maneuvers that add much to the scope of clinical electrophysiologic tests cannot be performed with surface His bundle studies. In contrast, temporary transvenous pacing leads can be positioned strategically for both pacing and recording localized endocardial signals.
in Cardiovascular
Diseases,
Vol.
24, No.
1 (July/August),
Techniques
Most commonly, transvenous pacing catheters are inserted percutaneously using the femoral veins, and are advanced to the heart under fluoroscopic control.‘s-‘7 The His bundle electrogram is somewhat more difficult to record from the brachial, subclavian, or jugular route, but may be accomplished with patience. Complex maneuvers and tip-deflecting catheters have been described for performing His bundle electrograms from the superior approachnm2’but are not really necessary.2’-22His bundle electrograms may be recorded during the withdrawal of a standard temporary pacemaker lead previously inserted by the subclavian route. Indeed, His bundle electrograms can be performed at the bedside without fluoroscopic assistance during the insertion of a temporary transvenous pacemaker by the superior approach.2’ Balloontipped leads, analogousto Swan-Ganz catheters, also have been used.23
THEORY AND TECHNIQUES
Progress
Filtering13v14
From the Department of Medicine, Division of Cardiology, Montejiore Hospital and Medical Center, and the Albert Einstein College of Medicine. Bronx, N. Y. Reprint requests should be addressed to John D. Fisher. M.D., Cardiac Catheterization Ofices. Montefiore Hospital and Medical Center. 111 East 210th Street, Bronx, N.Y. 10467. o 1981 by Grune & Stratton, Inc. 0033-0620/81/2401-0002$05.00/O
1981
25
26
Choice of Intracardiac
JOHN
Signals (Fig. I)
His bundle studies usually are recorded with a tripolar catheter draped across the tricuspid valve for recording the filtered localized signals of the low medial right atrium His bundle and right ventricular inflow. Another lead is positioned in the high right atrium at the junction of the superior vena cava for pacing and recording near the sinus node. For more complex studies, such as those involving tachycardias, additional leads (often of a multipolar design) are inserted. The coronary sinus lying in the atrioventricular groove presents a convenient transvenous approach to recordings of the left atrium and left ventricle. Influences on the Timing of Cardiac Intervals
Changes in sympathetic and parasympathetic tone can profoundly influence the heart rate and timing of the cardiac intervals.24’25 Such changes in neurohumoral tone can be brought about by anxiety, exercise, and other voluntary and involuntary factors. Fortunately, changes in autonomic tone do not appear to exert significant influences during electrophysiologic testing.26 Impulse formation and conduction also can be affected by factors such as ischemia and pharNORMAL
RANGES
(‘2 SD)
initial deflections
Fig. 1. Normal values and catheter positions for electrophysiologic studies. In this example, three ECG leads are displayed along with four intracardiac leads filtered at 4G-500 Hz: high right atrium (HRA). His bundle electrogram [HBE), low lateral right atrium (LLRAI, and coronary sinus (CS). Intervals are in milliseconds. Other abbreviations: SAN, sinoatrial node; RA, right atrium; LA, left atrium; TV, tricuspid valve; HB. His bundle: RV, right ventricle: LV, left ventricle. The P-A, A-H, and H-V intervals are explained in the text.
D. FISHER
macologic agents. Each of these factors must be taken into account when interpreting results of an electrophysiologic study. Baseline
Intervalsz7
The P-R interval may be divided into four parts. The P-A interval reflects conduction between the sinus node and the AV node and ranges (f 2 SD) between 9 and 45 msec.25 The A-H interval reflects conduction through the AV node and normally varies between 54 and 130 msec. The H-V interval (3&55 msec) is a measure of conduction in the His bundle and bundle branches (the His-Purkinje system), while the H potential gives information about the His bundle itself. Validation of the His Bundle Potential28*29
Deflections following the A wave may represent the atria1 “T” repolarization wave, part of the atrium, the His bundle potential, or a right bundle branch potential. When the apparent His bundle potential has been maximized for size and consistency, His bundle pacing should be attempted. Capture of the His bundle is recognized when the pacer impulse (PI) to QRS remains the same as the onset of the His bundle potential to QRS prior to pacing, and the QRST configuration is the same as during normal sinus rhythm during His bundle pacing. There are, however, two exceptions to these rules. (1) His bundle pacing may result in atria1 capture or in retrograde conduction to the atrium, and the retrograde P wave may distort the QRS complex. (2) Patients with bundle branch blocks during normal sinus rhythm may exhibit normalization of the QRS complex during His bundle pacing. This is ascribed to longitudinal dissociation within the His bundle, with the bundle branch block caused by disease in committed fibers proximal to the location of His bundle pacing.30p31 Establishing Onset of Ventricular Depolarization
The significance of a prolonged H-V interval has been the subject of much dispute,32-35 partly because investigators differ in the definition of the H-V interval itself. The H-V is measured
ELECTROPHYSIOLOGIC
27
TESTING
variously from the onset of the His bundle depolarization to the onset of the QRS in the peripheral ECG (sometimes called the H-Q interva1);33,36to the onset of the V in the intracardiac lead;” or to the onset of the ventricular depolarization wherever it is observed first.34.38 Since the purpose of measuring this interval is to establish the conduction time through the His-Purkinje system, it seems most reasonable to measure the onset of the ventricular depolarization in whichever lead it is observed first. Three mutually perpendicular peripheral ECG leads (leads, X, Y, and Z or leads 1, AVF, and VI) may not suffice to reflect accurately the onset of ventricular depolarization: in 23% of a series of 100 patients, recordings of the His bundle electrogram at 0.1-2000 and of the right ventricular apex at 0.1-2000 and 40-500 Hz resulted in an H-V interval at least 10 msec shorter than the conventional H-V interval recorded at 40-500 Hz alone.13 Electrophysiologic
Stresses
depressant effects on both sinus and AV nodes, carotid massage in patients with AV nodal Wenckebach generally results in worsening of the block. If the Wenckebach is at the HisPurkinje level, the slower sinus rate gives the His-Purkinje system more time to recover, and thus the degree of block may be improved. CSM should generally be avoided in patients with carotid bruits or histories of cerebral vascular accidents. Ventricular arrhythmias have occasionally been reported with CSM,S4,55typically associated with digitalis therapy. A reversal or mirror image of this test can be accomplished by using atropine. Diseaseof both sinoatrial and AV nodes in the same patient is common.57In a patient with sick sinussyndrome who responsds to carotid massage with sinus arrest, atria1 pacing during CSM will reveal whether AV nodal hypersensitivity also exists, This information can help determine whether an atria1 or ventricular pacer is appropriate for that patient.
and Maneuvers
In addition to data collected during passive recordings in normal sinus rhythm, stressescan be applied to specific parts of the conduction system. Carotid Sinus Massage (CSIV)~,~~-~~ CSM results in three types of cardiovascular effects: (1) cardioinhibitory (sinus arrest, AV block), (2) vasodepressor(hypotension), and (3) cerebral, i.e., syncope without bradycardia or hypotension, possibly due to cerebral ischemia and typically seenonly with prolonged CSM.39,40 The relative incidence of these signs in normal subjectscompared to those with syncope or overt cardiovascular disease has been the object of considerable investigation and controversy.8,39d8 CSM exerts its cardioinhibitory effects primarily on the sinus node (especially right CSM) and AV node (left CSM), resulting in slowing of the sinus rate and prolongation of the P-R interval or AV block due to lengthening of the A-H interval.39ds Block in the His-Purkinje system due to carotid sinus massageis distinctly rare, although it has been reported.56 In patients with Wenckebach phenomenon, CSM is often useful as a bedside test to determine the location of the block. Because of its
Exercise Exercise results in a number of neurohumoral changes, including a decrease in parasympathetic and an increase in sympathetic tone. Heart block at the level of the AV node may be improved by exercise and that due to HisPurkinje system diseaseworsened.59 Breath Holding In five normal subjects,60breath holding for as long as possible during maximum inspiration and during maximal expiration resulted in insignificant changes in the cardiac rhythm and rate. Some patients, however, exhibit profound changes.The most extreme examples are seen in patients suffering from the sleep apnea syndromes, who may have prolonged sinusarrest or heart block and during pacing develop Wenckebach at very low rates6’y6* Psychologic Stresses Many episodesof syncope or suddendeath are preceded by a period of psychologic stress.63 During electrophysiologic testing, psychologic stressescan influence the basic intervals, usually resulting in an increased sinus rate and shortening of the A-H interval.64
28
Incremental
JOHN
Pacing
The pacing rate is increased, usually in 10 beat per minute (bpm) steps, for a time sufficient to allow a steady-state response or “accommodation”65 to develop. This time may be as little as a few seconds or as long as 45 sec. Burst Pacing While the patient is in spontaneous rhythm the pacemaker is turned on suddenly, usually for a short burst of 10 or 20 stimuli. Bursts, designed to produce 1: 1 capture, may be at any rate, but the effects are most noticeable at short cycle lengths. Bursts are most commonly used for the induction and termination of tachycardias. Trains Short series of rapid stimuli designed to effect a single capture. Ramp Pacing Cardiac refractory periods are dependent on the preceding cycle lengths, and a sudden rapid burst may result in 2:l capture because of the long refractory period generated by the slow spontaneous rhythm. With incremental ramp pacing, higher rates with 1:l capture can be achieved because pacing is begun at a low rate and gradually increased over a period of seconds until a target rate is achieved or 1:l capture finally is lost. Because the refractory period is set by the preceding cycle length, which is being shortened continuously, the refractory period also shortens, allowing a higher maximum rate with 1:l capture than is possible with burst pacing. Rapidly incremental ramps are useful for induction and termination of tachycardias. Very slow ramps may be useful for assessing refractory periods of normal and abnormal pathways (see below). Decremental ramps, with gradual reduction in pacing rate, may help in the termination of some tachycardias. Programmed Programmed
Extrastimuli (PES) and Electrical Stimulation (PES)
The Extrastimulus Technique During the baseline rhythm, which may be spontaneousor paced, extrastimuli are adminis-
D. FISHER
tered by a special pacemaker that can be programmed to deliver the extrastimuli at any desired point during the cardiac cycle. In practice, the PES usually begins late in diastole and is repeated with increasing prematurity until the refractory period is reached. The stimulus conventionally is limited to between two and four times the threshold for capture. At lower outputs, erroneous interpretations are possibleif the threshold changes slightly. At higher outputs, there may be increased risk of “nonclinical” fibrillation, although a more accurate estimation of the absolute refractory period is possible. Eight or more beats occur between each PES to allow full return to the basic rhythm. Multiple as well as single PES may be used. PES are used in sinus node function tests, in the determination of cardiac refractory periods, and in the initiation and termination of tachycardias. Each of these roles will be described in detail below. Pharmacologic Stresses (Table 1)8*66-73 Pharmacologic agents affect different portions of the cardiac impulse formation and conduction systems allowing specific stressesor manipulations. Drugs chosenfor use will depend on the problem of the patient undergoing study. The effects of commonly used drugs, outlined in Table 1, suggest the difficulty in making a rational choice of agents. Additional new drugs are undergoing clinical trials and may have their own unique properties.69*72-76 Agents widely used for other purposesmay have potent electrophysiologic effects.79-8’ Attempts to classify drugs according to their cardiac electrophysiologic effects have enjoyed some success,69*70,82-84 but frequent exceptions have made these schemes rather cumbersome. The pharmacokinetics and duration of action of each agent must be considered, especially if the effects of several agents are to be tested.“-” Drugs such as lidocaine and edrophonium have relatively short half-lives. After a single bolus of 100 mg, lidocaine blood levels become subtherapeutic in as little as 6 min.‘* When rapidly infused, procainamide’s electrophysiologic effects may be undetectable after 1 hr.89Most other agents are longer lasting, and if separate studieson several are required, it may be necessary to extend the testing period over several days.
ELECTROPHYSIOLOGIC
TESTING
29
30
JOHN
THE “COMPLETE”
Sinoatrial
Node
(Table 2). Abnormal heart rates due to excessive autonomic tone may occur even if the sinus node itself is normal, i.e., a “pseudo-SSS” exists.
ELECTROPHYSIOLOGIC STUDY
(SAN)
Function
Tests
Carotid Sinus Massage
Pathophysiology of the Sick Sinus Syndrome (SSS)
Prolonged sinus arrest or AV block with carotid sinus massageor pressure in a patient with recurrent syncope are probably grounds for implantation of a permanent pacemaker.5~52
The SSS9W92is a collection of conditions, rather than a single entity, and is characterized by a sinus mechanism with an atria1 rate that is inappropriate for physiologic requirements. Unphysiologic bradycardia and tachycardia may coexist in the sameindividual as the brady-tachy syndrome (BTS). The tachycardia part of the BTS may be due to atria1 fibrillation or AV nodal reentrant supraventricular tachycardia, which is not surprising in view of the frequency of multilevel disease.s7 Inappropriate sinus tachycardia may be due to increased automaticity or to reentry and will be discussedin a later section. Sinus bradycardia may be caused by several mechanisms, each of which must be sought during a complete electrophysiologic study:93*94(1) intrinsic depression of automaticity, (2) conduction block in the sinus node and perisinus nodal tissues, and (3) hypersensitivity to autonomic influences, especially vagal tone. A battery of tests have been developed to help distinguish among the different forms of SSS
Table
Intrinsically
SA node
poor
2.
Sinus
Node
Function
automaticity
Wagal
tone
sensitivity
prolongs
Sinus Node Recovery Times (SRT, SNRT) One of the characteristics of automatic foci such as the sinus node is “overdrive suppression”: pacing at rates in excess of the spontaneous rate of the automatic focus results in a temporary inhibition of spontaneousdepolarization of the automatic focus, with gradual return to the original cycle length over several beats after cessation of pacing. In normal patients, pacing the atrium at approximately 120 bpm for a minimum of 15 set results in reproducible sinus node recovery times defined as the interval from the last pacing impulse until the first sinus node recovery beat.” by the third recovery beat, the sinus rhythm has returned to the basic cycle length f 250 msec (Fig. 2, normal response). The normal range of SNRTs (Table 3) varies widely among investigators,27~9”‘osmaximum durations approximating 1500 msec being typi-
Tests
in Apparent
Sick
Sinus
Expected Vagal
Sinus Node
Tone
Test
Decreased
CSM SNRT
to normal
sinoatrial
tone
conduction
times.
Rapid
Increased
CSM SNRT SACT
Decreased
CSM SNRT SACT
pacing
used
Syndrome
Result Further
durig
the
SNRT
test
slowing
Prolonged Normal Further slowing*
SACT CSM SNRT SACT
Decreased
block
Vagal hypersensitivity Excess vagal tone
Excess
D. FISHER
Variable Prolonged Little change Variable* Prolonged* Further slowing Normal+ Normal may
fail
to penetrate
hypervagotonia exists, thus failing to cause overdrive suppression. However, exit of sinus beats may also be impeded. TTachycardia (pacing) induced vagal tone may result in prolongation. Secondary pauses may occur if vagal tone increases hypertension related to initial recovery beats. CSM: carotid sinus massage; SACT: sinoatrial conduction time; SNRT: sinus node recovery time.
the
sinus
node
in response
if to
ELECTROPHYSIOLOGIC
31
TESTING
Fig. 2. Sinus node recovery time schematic. The heart rate and cycle length are represented on the ordinate. The first part of the abscissa is compressed and represents several minutes of baseline sinus rhythm and atrial pacing. Subsequently, the abscissa is calibrated in numbers of recovery beats following cessation of atrial pacing. The heavy line represents the normal response: from a baseline sinus rate (NM) of approximately 70 bpm the patient is paced at a rate of approximately 125 bpm. Upon cessation of pacing the first recovery beat normally occurs in less than 1500 msec and the rate returns to baseline after a few beats. The lighter lines show typical abnormal responses (see text).
Atrial ‘i
I\Pacing
\
off t
I JSR
cal. Corrections for differences in the baseline sinus cycle length commonly are applied. The corrected sinus node recovery time (SNRTC or CSNRT) usually is calculated in one of four ways. (1) The basic sinus rhythm cycle Iength in msec is subtracted from the sinus node recovery time to give the CSNRT with normal ranges varying between 350 and 550 msec. (2) The corrected sinus node recovery time is expressed as a percentage of the baseline cycle length, normal values ranging up to 180%. The uncorrected sinus node recovery time appears to differentiate between normal and sick sinus node patients at least as well as these corrections (Table 3). (3) Regression equations have been proposed9’.‘06 with an upper limit of normal SNRT of 1.3 (means sinus cycle length in msec) + 101 msec. (4) Clinical dennervation of the sinus node94 using 0.2 mg/kg of propranolol followed by 0.04 mg/kg of atropine results in an “intrinsic sinus rate.” This method may help to distinguish patients with true sick sinus syndrome from those whose normal sinus nodes are under the influence of excessive vagal tone.
I
I
1
2345678910
I
I
RECOVERY
I
I
I
I
I
1
BEAT
Pacing at 120-l 30 bpm for 15 set produces reproducible results in normal subjects, i.e., a scatter of less than about 250 msec on successive trials, with little differences if pacing is carried out for a longer period of time.95-97*lo7 Normals may show a modest decrease in the SNRT after faster pacing95~97*‘0’due to autonomic adjustment to pacing-related anxiety or hypotension. Abnormalities seen in patients with SSS are outlined in Fig. 2, and include the following: (1) markedly prolonged SNRT; (2) a wide scattering of the SNRT when many trials are carried out;“’ this or short SNRTs may indicate failure of some pacing stimuli to enter the SAN, i.e., some degree of SAN block. (3) prolongation of the SNRT after pacing at more rapid rates or for longer periods in patients where normal values were observed with slower pacing rates or durations? (4) the normal response after an SNRT is a gradual return to the baseline cycle length that usually occurs within 3-4 beats. A “secondary pause” exists if the beats following the sinus node recovery time do not return to normal and the sinus rate remains depressed, or if there is a return to normal with a subsequent persistant or transient decrease in rate.“’ (5) Ectopic beats or rhythms.
15
93,105
ID4
299
57
11
-
20
ID3
1,044
30
1,062
921
1,lDo
-
102
-
too 101
1,026
20
958
-
99
452
98 32
34
27
97
-
1,041 -
43 27
95
996
SNRT
Subjects
Ref
MM”
Number
207
172
-
12571
1,499t
1,476
1.265
1,476
1,460
216
190
1,342
1,256
-
1,680
1.775 -
+zstl
-
lmsecl
-
158
149
-
346
367 -
*SD
SNRT
Normals
w
Table
29%
16.5%
129%
131 -
113
119
-
23%
155
107
-
279
96
6.6%
*SD
SNRTc*
Sinus
133
-
3.
232
210
270
295
-
134%
252
180
119% -
171
260
SNRTc
Mea”
Controls
1245)
519t
-
496
-
472
496
533
-
562
394
-
456 729
-
+ZSD
“Isac
Node
BY
I1911
l6l+
162
-
_-
--
-
-
180
-
-
177 .-
159 -
137
-I- 2SD
PWCB”t
Recovery
3
N
-e
13
14
17
41
19
19 -
14
19
26 -
Times
-
1.361
1,006
-
2.110
1,401
2.064
2.209
-
-
4,732 -
SNRT
Mea”
(SNRT)
306 -
249
-
1,269
393
1,326
1,096
-
-
719 -
*SD
SNRT
1.977 -
1,504
-
4,646
2.187
4.720
4.402
-
-
6.170 -
+2SD
o(
Max
130%
276
680 -
1,016
-
961 -
1,133
147%
31%
293
-
1,335
-
864
-
3.350
3,362
-
1.183
3,467 -
3,376
1,253 -
1,122
3.110
1,092 -
-
ZSD
1.009
23
SNRTc
-
Syndrome
+SD
Sinus
SNRTc
MW”
Sock
BY
192
-
-
-
-
-
193 -
-
-
-
+ZSD
Percent
61
I
I
I
73 53
37 94
SNRTc bv %
SNRTc SNRT 22
SNRTc SNRT
SNRTc SNRT
SNRTc SNRT
26 35
14
35
-
I 10379
-
-
100
Percent A”W”Wl*
ELECTROPHYSIOLOGIC
TESTING
SAN
NSR
ATRIUM ZONE
1
Non-Reset AIA~= ~AIAI AZAJ Prolongs Fig. 3. Sinoatrial conduction time schematic of premature beat method (Strauss at al. sea text). The sinoatrial node (SAN) depolarizes unseen and results ultimately in atrial depolarization, designated here as Al. In performing this test, premature atrial beats (A21 ara introduced with increasing prematurity and the timing of the return cycle lA3) is analyzed. The sinoatrial conduction time is calculated from zone II responses.
ZONE
2*
Reset AIAW ~AIAI AzAs Constant
ZONE
3
SAN Entry Block AIAJ~AIAI (AZ lnterpobted ) ZONE 4 ?SAN Reentry AI A3 < At AI (SAN Gap)
*SACT=A~J-A%I
The Sinoatrial Conduction Time (SACT, Sinoatrial Block Test) Direct recording of low-amplitude sinus node potentials requires microelectrode techniques in vitro’09.“0 or special equipment in vivo.“‘,“2 Clinically, two indirect tests of sinoatrial conduction are in use. The first, described by Strauss et al. (Fig. 3)98 involves programmed extrastimuli (PES) given in the region of the sinus node during sinus rhythm (designated Al). Premature beats not resulting in reset of the sinus node are termed zone I. Zone II occurs when the PES (A2) is given with sufficient prematurity so that it can enter into the sinus node and depolarize it prematurely. This results in a pause that is less than compensatory. The return beat, designated A3, is presumed to originate in the sinus node exactly one basic cycle length (Al Al) after the
/
NSR
\
ATRIAL I
SACT=
PACING
AX~-~I
(Divide
by 2 for l-way
SACT)
node has been reset by the A2. Earlier premature beats in zone II may depress sinus automaticity to some degree, resulting in a prolongation of subsequent spontaneous cycles, A3A4,9”,“3 or a shift in sinoatrial pacemaker.‘14 Later premature beats in the one-third of zone II adjacent to zone I may give more meaningful results. This area has been designated zone IIa.98 With increasing prematurity of A2, the onset of zones III and IV is heralded by a cacophony of responses. Narula has described a second method of estimating the SACT not requiring the use of special pacing equipment (Fig. 4).“’ It assumes that pacing the atrium at rates of 10 bpm or less above the sinus rate will not result in significant overdrive suppression of the sinus node, but that the pacing beats will gradually achieve capture and reset of the sinus node. These two methods
RATE SLIGHTLY
ABOVE
(Divide by 2 for l-way
NSR \
RECOVERY
SACT)
Fig. 4. Sinoatrial conduction time schematic. Atrial pacing method {Narula). Once again, the sinoatrial node depolarizes unseen and ultimately results in an atrial depolarization (Al I. Instead of premature beats, atrial pacing at a rate slightly above that of the sinus rate is used as A2. It is assumed that such atrial pacing will ultimately depolarize the sinus node without significant overdrive suppression. The sinoatrial conduction time is then calculated as for the premature beat method (see text).
34
JOHN
result in somewhat similar values for the SACT, but the importance of disparities is not yet resolved.1’6 Sinoatrial conduction times in patients with and without evidence of sinus node disease (Table 4). 93,97-‘oO.‘OZ,‘O4.“7The upper limits of normal (+2SD) in 176 patients (Table 4) is 147 msec using the Strauss technique and “one-way” SACT. The total or 2-way SACT would be 294 msec (+2 SD). Some investigators consider SACTs beyond + 1 SD as abnormal.98 Normal ranges for the Narula method have not yet been established, as previous reports”5s”6 have combined data from patients with and without sinus node disease.
normal response to 1 or 2 mg of intravenous atropine is an increase in the sinus rate to 90 bpm or 20% above the baseline level.90*98Sinus node recovery times performed in the presence of atropine generally are shorter than baseline,lz3 but paradoxical prolongations have been described.‘24 It is possible that in these patients atropine permits 1: 1 entry of the pacing impulses into a diseased sinus node and a greater degree of suppression than was possible without the drug. The combined use of atropine and propranolol has been discussed above.94 LidoCaine, 100-l 50 mg intravenously, and edrophonium, 15 mg intravenously in divided doses of 7.5 mg 1 min apart, do not significantly affect the sinus node recovery time in normal subjects.‘25,‘26 In patients with the sick sinus syndrome, however, marked prolongation may occur in response to these drugs, even when the sinus node recovery time was normal prior to their administration.‘25.‘26
Sinus Node Function in Ischemic Heart Disease Acute myocardial infarction can produce sinus bradycardia and marked prolongation of the SNRT,‘18q”9 although the overall incidence of overt sinus node dysfunction is not high, occurring in 20 of 43 1 patients in one series.“’ In the presence of other indications for temporary pacing, evidence of sinus node abnormalities during acute infarction occurred in 17 of 49 patients.12’ Among patients with chronic coronary artery disease, stenosis proximal to the origin of the sinus node artery is associated with abnormal sinus node function tests, with the SACT more sensitive than the SNRT.“’ Carotid sinus hypersensitivity also is common in the presence of coronary artery disease.12’ Pharmacologic
Clinical Usefulness Function Tests
Pharmacologic agents have been used in the assessment of sinus node function (Table 1). A 4.
Sinoatrial
Conduction
of Sinus Node
Most investigators have concentrated on the ability of sinus node function tests to distinguish between patients with known sinus node disease and a control population. The question of whether therapeutic action should be taken on the basis of normal sinus function tests has been addressed less frequently. In a patient with unexplained syncope, a sinus node recovery time of 5 set probably would lead to the implantation of a pacemaker. Whether a pacemaker should be implanted for values just outside the normal ranges is less clear. In
Stresses
Table
Times
(SACT):
“One-way”* Sect Sinus
Max
A”dlO,S
Reference 88 -
35 -
Syndrome
Number
Mean
Max
+2SD
Of
6ACT
+ 2SD
lmsecl
Subjects
169
or
*SD
(ms-scl
46 -
206 -
20 -
16
86
43
180
27
19 -
113 -
66 -
226 -
47 (1001
hsecl
65
22
128
92
30 -
162 -
62
18
120
18 41
181 12s
18 47
217 219
30
172
14
128
27
182
29
143
24
124
68
240
112 86
cf
113 -
24 -
120 -
-
D. FISHER
41 0 26
ELECTROPHYSIOLOGIC
TESTING
elderly patients with sinus bradycardia and symptoms, a prolonged corrected sinus node recovery time may militate strongly in favor of pacemaker implantation.‘27 The value of sinoatrial conduction tests often is diminished by uninterpretable results (e.g., “scatter” graphs12’), but definitely abnormal sinoatrial conduction times are associated with a very high incidence of overt sinus node disease.“’ Nevertheless, an abnormal sinoatrial conduction time in an asymptomatic patient does not warrant the implantation of a pacemaker.“’ The likelihood of recording diagnostic abnormalities in a patient with previously documented sinus node disease increases with the number of variations of sinus function tests employed. At present, the minimum abnormalities that justify the implantation of a pacemaker remain a matter of individual opinion. The Atrium Conduction
From Sinus Node to Atrium
Earliest activation of the atrium typically occurs in the high right atrium near the junction of the superior veaa cava. Earliest activation may, however, occur elsewhere, often in the midlateral right atrium.‘29 This is consistent with the concept of the sinus node as an elongated structure with multiple pacemaker cells whose dominance may shift with autonomic tone, with multiple points of possible exit into the atrium.‘30*‘3’ Internodal conduction is recorded as the P-A interval or, during pacing, as the PI-A. Three specialized internodal pathways have been proposed: anterior, middle, and posterior, somewhat analogous to the His-Purkinje system in the ventricle.‘32.‘33 This concept is supported by demonstration of sinoventricular conduction’34 and its mirror-image (high atrium depolarized first in some subjects during ventricular pacing and retrograde conduction),‘35 animal studies,‘33 and production of AV dissociation during surgery involving areas traversed by the pathways.131 Pacing at different sites may alter the A-H interval. Left atria1 pacing may cause a shorter A-H interval at a given pacing rate than does high right atrial pacing,‘36,‘37 possibly due to a lower insertion of the posterior internodal tract into the AV node. However, others have found no change or inconsistent changes in the A-H, depending on pacing site.“’
35
There is some dispute about the internodal pathways. In humans, these pathways do not consist of continuously linked specialized conducting cells.‘39 Rather, these cells are common throughout the subendocardial layer of the atrium’40,‘4’ but may occur with increased frequency along the routes of the intranodal pathways, which in turn occur along thicker bands of muscle that might in themselves facilitate more rapid conduction. With incremental atria1 pacing, the P-A interval, redesignated PI (for pacer impulse) to A interval, may remain unchanged, but pro10ngs’42,‘43 in as many as 60% of patients by 15 msec or more.‘42 This prolongation usually occurs at the lowest pacing rates but sometimes is delayed until faster pacing. Whether the PI-A remains constant or prolongs does not appear to be related to specific cardiac diseases or to normalcy, but appears to be a random phenomenon. It may be that where the PI-A prolongs, the impulse has failed to gain access to the specialized conduction system of the intranodal pathways or perhaps that in these patients, such specialized pathways do not exist as functional entities. There may also be a period of “latency” between stimulus and atria1 response, but observations in our laboratory, using closely spaced quadripolar leads, suggests that PI-A prolongation is due to slowed conduction rather than latency. Interatrial conduction’44’46 in dogs proceeds via a superiorly situated Bachman’s bundle and an inferior pathway.‘44S’45 In man, these pathways are as evasive histologically as the internodal tracts. Programmed extrastimulation of the atrium is used to determine sinus node conduction times and atria1 and conduction system refractory periods, discussed in a greater detail later. Refractory periods normally are similar in different parts of the atrium. Marked dissimilarities may predispose to arrhythmias. Vulnerability to PES, i.e., the induction of tachycardia, also will be discussed below. The Atrioventricular
Node (AVN)
The functional status of the AV node during sinus rhythm is estimated from the A-H interval, which normally ranges between 54 and 130 msec.
36
Eflect of Neurohumoral
JOHN
Influences
The function of the AV node is influenced strongly by sympathetic and parasympathetic tone. 24*25~‘47~148 Periods of Wenckebach seconddegree AV block, presumably at the AV node, have been described in normal medical students’4g and in athletes”’ and ascribed to increased parasympathetic tone, but more serious conduction disturbances may exist in some of these subjects.‘s’
D. FISHER
such as anxiety and hypotension. With pacing, the A-H interval prolongs, with 70% of normal adult subjects developing Wenckebach at the level of the AV node at rates lower than 190 bpm.*’ In children, the rate at which Wenckebath appears is considerably higher, over 200 bpm,‘53 but is still lower than the rate at which Wenckebach occurs with exercise. Taking two standard deviations from the mean as the normal range, some normal subjects may develop Wenckebach at rates barely over 100 bpm with atria1 pacing*’ (Figs. 5 and 6).
AV Node Conduction In animals, there is dual spread of excitation in the AV node from a posterior input via the crista terminalis, and an input anterior to the coronary sinus.“’ These may correspond to the inputs from the internodal tracts that are postulated to exist in humans.‘32T’33 The posterior tract enters lower in the node, accounting for shorter A-H times during left atria1 pacing and may result in partial AV node bypass (see below Lown-Ganong-Levine syndrome). The AV node has been divided into an AN zone between the atrium and the node; an N zone of the node proper, with slow response action potentials accounting for slow or decremental conduction; and an NH zone between the node and the His bundle.“* The AV node may be envisioned as a network of potential pathways with somewhat variable refractory periods and conduction properties. Excitation in the AN and N zones is not well synchronized but occurs over a broad front, though wavefronts resulting from anterior and posterior inputs ultimately merge to activate the central nodal area, resulting in synchronous activation in the NH zone.15* During retrograde conduction, the pattern is not exactly reversed, as the anterior area in the interatrial septum is depolarized before the crista terminalis.“’ Fundamental Difference Between A-H Intervals With Exercise and With Pacing With exercise there is little change in the P-R and A-H intervals due to a decrease in parasympathetic and an increase in sympathetic tone, allowing the AV node to cope with the increased number of stimuli reaching it. With incremental atria1 pacing, however, autonomic tone is changed only indirectly in response to factors
incremental
Atria1 Pacing
If one plots the A-H interval against the heart rate in normal subjects, a smoothly rising curve is inscribed. In patients with the Lown-GanongLevine syndrome (AV nodes bypass or enhanced AV node conduction), there may be little or no increase in the A-H interval with incremental pacing. In patients with dual AV node pathways, a sudden break in the curve may be observed as the refractory period of the fast pathway is reached and conduction shifts to the slower pathway. These abnormal situations will be described in greater detail in the sections below dealing with tachycardias. Conduction Velocity and Refractory the AV NodeIs
Periods in
In most tissues the refractory period shortens with decrease in basic cycle length (increase in heart rate), and conduction velocity is altered little. In the AV node, the relationships are more complex. Conduction velocity decreases with decreasing cycle length during atria1 pacing, resulting in A-H interval prolongation. At shorter pacing cycle lengths, the refractory period defined by atria1 extrastimuli is found to shorten, and a beat of a given prematurity is conducted more rapidly during basic pacing at faster rates. Rapid Prolonged Pacing Some diseases of the AV conduction system, such as Lev’s or Lenegre’s diseases, result in fixed abnormalities within the conduction system. Ischemic heart disease, on the other hand, may result in a more dynamic abnormality,ls5 and prolonged rapid pacing at rates suffi-
ELEClROPHYSlOLOGlC
37
TESTING
NSR
RATE 60-00
380
60360 340
70
39
70-80
29
80-90
15
go-100 TOTAL
320
N27
8 119
300 280 260 240
Fig. 5. The A-H interval during normal sinus rhythm and during high right atria1 pacing. This is based on 119 adult subjects without evidence of AV node disease on the peripheral ECG; with normal intervals on the baseline sinus rhythm His bundle electrogram; and without evidence of enhanced AV node conduction during atria1 pacing (unpublished data from our laboratory). On the ordinate is the A-H interval in msec. On the abscissa: on the left the A-H interval during normal sinus rhythm et rates between 60 and 100 bpm. In the center, the A-H interval of the total group with a mean heart rate of 72 bpm. On the right, effect of atrial pacing on the A-H interval. Five lines (solid, dashed, and dotted) represent the mean and +l end k2 SD.
220
I--
s 200
l--
LO 160 140
,--
120
I--
100
l--
-
80
I--
-
6C
l--
40
I--
20 l-1
5’0 NSR
7’6 100 RATE
cient to induce ischemia may unmask abnormalities otherwise hidden in the conduction system. Ventricular
TOTAL
80 ATRIAL
120 WCIW
RATE
100 (n=llQ)
200
pathways also can be diagnosed using incremental ventricular pacing.
Pacing
Retrograde conduction from ventricle to atrium does not occur in all normal subjects,64 but when present, utilizes the normal conduction pathway, including the AV node, in a retrograde fashion. With incremental ventricular pacing, the VA interval gradually prolongs, ultimately resulting in a Wenckebach. As with antegrade conduction, a smooth curve normally is inscribed, but flat curves (indicating some degree of AV node bypass) and dual AV node
Echo Beats The AV node is a network of potential pathways most of which have similar conduction and refractory characteristics in normal individuals. Nevertheless, a premature beat may find one pathway refractory so that the impulse travels antegradely down another pathway. Ultimately, the pathway that previously was refractory now conducts the impulse retrogradely into the atrium resulting in an AV nodal echo beat.
38
JOHN
D. FISHER
\ = Rate where this patient developed Wenckebach Meam154: 26 n= 118pts
80
60
I
80
I
I
I
I
120 160 ATRIAL PACING RATE
Pharmacology Medications such as edrophonium, proprano101, and verapamil depress AV node conduction (Table 1). Procainamide, quinidine, and disopyramide may depress conduction directly, but their vagolytic effects enhance conduction and the overall effect is unpredictable. Digitalis may depend on an intact vagal system for its depressant effect on the AV node. Isoproterenol and atropine directly facilitate AVN conduction. Chronic A V Node Block Congenital complete AV block typically occurs at the AV node.‘56 Many of these patients have reliable junctional rhythms and their growth and development may be normal. With exercise, junctional rates increase but not to a degree equivalent to that seen with conducted sinus rhythms. Cardiac output requirements must then be met with an increased stroke volume, and hence, cardiomegaly develops. Most physicians would opt for the implantation of a
I
I
200
I
I
220
Fig. 6. Atrial pacing at which Wenckebach at the A-H level develops in patients without evidence of AV node disease on the resting ECG or baseline His bundle electrograms (unpublished data from our laboratory). On the ordinate is the percentage of patients with normal AV conduction who develop Wenckebath at the AV node, and on the abscissa is the atrial pacing rate. We find it useful in preparing electrophysiologic reports to use this graph, with an arrow marking the point at which the individual undergoing studies developed Wenckebath. In this group of 118 adult subjects, Wenckebach developed at a mean rate of 164 f 26 ISD) bpm.
cardiac pacemaker at the point when either cardiomegaly or symptoms develop. An atria1 synchronous pacer (VAT; VDD) is especially physiologic in active subjects such as growing children. Junctional recovery times (JRT) have been reported, analogous to SNRTs, following atria1 or ventricular pacing.i5’ A corrected JRT (CJRT = JRT - basic cycle length) of 200 msec or less, either in baseline state or after 2-2.5 mg atropine, was typical of asymptomatic patients whether the junctional pacers were located in the AV node or bundle of His. Those with longer CJRTs may require pacing. Myocardial infarction and the AV node will be discussed in conjunction with the HisPurkinje system. Clinical Implications of AV Node Block or Disease Patients with AV node disease are at an increased risk of syncope’” and progression to
ELECTROPHYSIOLOGIC
39
TESTING
complete block, if not already present.151~‘58 Myocardial dysfunction is more likely to exist in combined AV node and bundle branch disease than in the latter alone.“’ Overall mortality is not high, however, with AV node block.15’ The His-Purkinje System (Infranodal Conduction, H-V Interval)
Incremental Atria1 Pacing With incremental atria1 pacing the H-V interval normally remains constant, with block or H-V prolongation representing a pathologic finding associated with subsequentdevelopment of AV block and sudden death.159As with the AV node, blockages in the His-Purkinje system also may be dynamic, especially if related to ischemia. Programmed Extrastimuli (PES) The H-V interval usually remains stable with increasingly premature PES, as the refractory period of the AV node is usually longer than that of the His-Purkinje system. The role of the His-Purkinje system in tachycardias has been studied using PES, as have antegrade and retrograde refractory periods and “gaps.” All these will be discussedbelow. Retrograde Conduction: Incremental Ventricular Pacing and PES’6G’62 The His bundle potential is difficult to record during retrograde conduction. Catheters with a very small interelectrode distance (1 or 2 mm) may increase the chances of recording a His bundle potential by increasing the localization of the recordings.“j’ Retrograde block is encountered commonly in the AV node, but delays in or below the His bundle also occur.16oRetrograde conduction is not predicted by the degree of integrity of anterograde conduction or by bundle branch block.16’With PES in the right ventricle, retroconduction usually is via the left bundle branch.16* Pharmacologic Agents and the His-Purkinje System Procainamide is the most useful agent presently available in the United States for stressing of the His-Purkinje system (Table 1). Intrave-
nous dosesof 10 mg/kg over 15 or 20 min may prolong the H-V interval in normal patients and cause rather striking prolongations in patients with bundle branch block.‘633’64 In somepatients with syncope or dizziness, procainamide may result in complete heart block at the H-V level. The Europeans report similar findings with ajmaline.j6’ Lidocaine, although rarely causing any H-V prolongation in normal subjects, may cause heart block at the H-V level in susceptible patients,‘66again typically those with symptoms and usually with bundle branch block. Because H-V block in responseto these medications is so clearly abnormal, implantation of a permanent pacemaker seems appropriate in symptomatic patients. Intra-Hisian Blocks (Split His Potentials)‘67-172 (Fig. 7) A block within the His bundle, reflecting very localized disease in the specialized tissue, is diagnosed by a broad multiphasic His bundle potential or two distinct His bundle potentials, both frequently accompanied by a normal QRS complex. Intra-Hisian block may be a particularly malignant condition, as transient heart block with a narrow QRS may be attributed to AV node diseaseand discounted. Carotid sinus massage often is revealing, with AV node Wenckebach worsening and intra-His or H-V block improving. Some consider a split His potential to be one of the few absolute indications for a permanent pacer on the basis of an electrophysiologic study, as most patients with split His potentials have had documented heart block or syncope.167-171 A recent report, however, has suggestedthat the prognosis of intra-Hisian diseasemay be more benign.“* A normal QRS in conjunction with a very long H-V interval also may represent balanced first-degree block within the bundle branches. Complete block of one bundle branch would still leave the other functioning. This may account for the more benign prognosisof somepatients who were felt to have intra-His block. In others, distal His bundle pacemakers may provide an adequate rate. A corrected junctional recovery time of 200 msec or lessmay save someasyptomatic patients from an implanted pacer.“’ There appears to be a predilection for split His potentials among elderly females,‘67.‘69 but it may be congenital or surgically induced.“’ Lidocaine and procain-
JOHN
A-A H-H’ WV
1306 8 50
1250 160 50
D. FISHER
X X
Fig. 7. Irma-His block produced by lidocaine. This elderly woman had a history of recurrent syncope and a normal electrocardiogram. Baseline electrophysiofogic recordings illustrated in the first panel, revealed the presence of a multiphasic or ragged His bundle potential. After the administration of 50 mg of lidocaine (middle panel), there was little change in the heart rate (AA interval). but the multiphasic His bundle potential has now split into two positions. In the third panel, following an additional 25 mg of lidocaine, there is complete heart block at the intra-His level. Such sensitivity to lidocaine is uncommon even in people with advanced His-Purkinje disease, but illustrates the need for caution in people with a history of unexplained syncope. While the AV node is the usual site of block in patients with a narrow QRS interval, the presence and potential malignancy of intra-His block should be considered strongly in patients with a history of syncope.
amide commonly produce complete block in this condition (unpublished observations) (Fig. 7). The Clinical Significance
of the H-V Interval
The clinical significance of a prolonged H-V interval is still a matter of lively dispute. Asymptomatic patients with very long H-V intervals are reported to enjoy a favorable prognosis,‘73 although longer follow-up periods are beginning to revise this impression.174 The clinician frequently must deal with the problem of a patient with syncope or near syncope in whom complete medical and neurologic evaluation, including ambulatory ECG monitoring, has failed to reveal a cause for the symptoms. The role of the H-V interval has been difficult to resolve because most studies have included all patients with bundle branch block even if asymptomatic.‘73-‘82 Other problems are generated by the inclusion of patients who may be symptomatic but have known prior intermittent heart block or other causes for symptoms such as sinoatrial disease or tachycardias.‘83*‘84 Few have assessed the role of permanent pacing in patients suspected of having intermittent heart block on the basis of a prolonged H-V interval. In one study,‘85 59 consecutive patients had symptoms suggestive of intermittent heart block, unrevealing medical and neurologic evaluations and
ambulatory monitoring, and His bundle studies that were normal {in one-third of the patients) or showed only a prolonged H-V interval. Half of the patients with long H-V intervals received permanent pacers. Progression to heart block did not occur among patients with normal H-V intervals. Among patients with prolonged H-V intervals, heart block was documented during follow-up in 25%; however, among the unpaced patients, progression to heart block was accompanied by recurrent symptoms, whereas in the paced patients, it was observed only as an incidental finding during pacemaker check-ups. Sudden death occurred only among unpaced patients in the long H-V group. By decreasing the number of variables, His bundle studies seemed to suggest that permanent pacing is appropriate for symptomatic patients with H-V intervals of 60 msec or more, in whom other causes for syncope are not apparent. Bundle Branch Block, Prolonged P-R Interval and the His-Purkinje System: Additional Considerations Based on electrocardiographic data alone, the overall risk of development of complete heart block in patients with bifascicular block appears to be less than 7%10% per year in hospitalized or cardiac patients, and much lower in asympto-
ELECTROPHYSlOLOGlC
41
TESTING
matic patients.‘86-‘89 Attempts to correlate the H-V interval with the peripheral ECG configuration have proved of statistical interest, but of little use for the individual patient. A prolonged H-V interval can be observed in patients with normal QRS complexes’85 and is the rule in patients with right or left bundle branch block combined with left axis deviation.‘903’9’ About one-quarter of patients with right bundle branch block will have prolongation of the H-V interva1,19’ but the incidence rises to 40%-70% when right bundle branch block is combined with left axis deviation and 66%-100% in right bundle branch block plus right axis deviation.‘9”92 Twothirds of patients with left bundle branch block may have a prolonged H-V interval.19* There is some question whether ventricular activation occurs later in isolated left bundle branch block compared to right bundle branch block.‘933’94 Although the addition of a first-degree AV block increases the likelihood of H-V interval prolongation in both right and left bundle branch block, more than a quarter of patients with any combination of “incompIete trifascicular block” will be found to have a normal H-V interval.19* Pseudo-complete bundle branch block has been described in which spontaneousor induced block of the other bundle reveals conduction through the supposedly blocked bundle, indicating that the “complete” block was, in fact, only firstdegree block.‘95The presenceof alternating right and left bundle branch block implies diffuse conduction system disease and most such patients probably should receive permanent pacemakers. Rate-dependent bundle branch block often is associated with cardiac disease’96 but most do not require permanent pacing.
Conduction System in Acute Myocardial Infarction Following acute myocardial infarction, highdegree AV block, new bundle branch block, or a prolonged H-V interval are associated with an unfavorable prognosis.‘97m2’2 It is not clear, however, whether permanent pacing would prevent subsequent mortality in these patients, which often is due to ventricular tachycardia, fibrillation, or pump failure as well as heart block. In some subjects, a repeat His bundle study performed just prior to discharge home
may reveal a return towards normal of the H-V interval, and this is associatedwith an improved prognosis.209Solitary left anterior hemiblock does not have a deleterious effect on prognosis*” but it may obscure concurrent RBBB unless unipolar V-leads are placed higher than usual and right chest leads are recorded.2’412’5 With an inferior wall infarction, left anterior hemiblock itself may be obscured but can be diagnosed by the presence of a terminal S in lead II and a terminal positive deflection in AVR.2’6 Inferior wall myocardial infarctions are classically associated with block at the AV node that usually is transient; anterior wall infarctions result in a more sudden and permanent block in the HisPurkinje system.*” Electrophysiologic studies during the course of acute myocardial infarction often reveals, however, that diseaseis more widespread and even in a different location than suggested by the electrocardiogram: sinus and AV node diseaseare not uncommon with anterior wall myocardial infarctions and H-V prolongation or intra-Hisian blocks are not unusual with inferior wall myocardial infarction. 2'7-220 Most current guidelines for implantation of a permanent pacemaker following acute myocardial infarction are derived from series using surface ECG data.
Multilevel Disease’.22’ Because of the high incidence of multilevel disease,atria1 pacing may not be appropriate for all patients with sinus nodedisease,although it is more desirable physiologically. Before permanent atria1 pacing is undertaken as treatment for the sick sinussyndrome, the physician should be satisfied that there is no significant conduction system disease. Concurrent diseaseof the AV node and HisPurkinje system is common. The combination of right bundle branch block, left anterior fascicle block, and first-degree AV block may not represent “trifascicular” disease at all: delay also could originate within the atrium or the AV node; or, because of longitudinal dissociation, the His bundle alone may be the site of apparent trifascicular disease. Intraatrial conduction delays may result in first-degree AV block and higher degrees of
42
intraatrial block may mimic peripheral cardiogram.
JOHN
AV block on the
Electrophysiologic Characteristics of Miscellaneous Diseases and Conditions Aortic valve disease.222*223 Aortic insufficiency and aortic stenosis may be associated with complete heart block. Block at the AV node is more common with aortic insufficiency, and block in or below the His bundle with aortic stenosis. Mitral valve prolapse.224S225 Mitral valve prolapse is associated with cardiac arrhythmias, including variations in the sick sinus syndrome and ventricular tachycardias (typically originating in the papillary muscles), which may account for the incidence of sudden death with this condition. Hypertrophic cardiomyopathy.226v227 Electrophysiologic testing in six patients with this condition revealed a normal A-H interval in all and a prolonged H-V interval of 60 msec in one patient.226 Heart block is not rare in this condition.==’ Congestive cardiomyopathy. H-V interval prolongation is common in congestive cardiomyopathy, especially in the presence of bundle branch block.22s The presence of conduction disease is not correlated with the degree of ventricular enlargement or end-diastolic pressure. Conduction abnormalities also are seen in alcoholic cardiomyopathy, with H-V interval prolongation again being more common than disease of the AV node.229 Infiltrative cardiomyopathy: Sarcoidosis, amyloidosis, and hemochromatosis.230*23’ Atria1 and ventricular tachycardias, sinus node disease, and heart block occur with unfortunate frequency in these conditions. His bundle studies may reveal abnormal sinus function tests as well as prolongation of the A-H and H-V intervals. Collagen-vascular diseases.232-234 As with the infiltrative cardiomyopathies, heart block and other arrhythmias may occur with collagen vascular diseases, particularly systemic lupus erythematosis. Congential complete heart block appears to be particularly common in newborns whose mothers have connective tissue disease. Infectious processes. Viral myocarditis may be associated with ventricular arrhythmias. Recovery from varicella myocarditis is uncom-
D. FISHER
mon, perhaps due to malignant ventricular tachycardias and fibrillation, although successful treatment of a case with mexiletine has been reported.*” Bacteremias also may result in heart block. Electrophysiologic studies on one 18-yrold girl with gonococcal septicemia revealed both intra- and infra-His bundle block, which persisted on restudy 6 mo after the acute episode.236 Chagas disease is a common cause of heart block and tachycardias in South America 237.238 Thyroid disease. Sudden death, ventricular arrhythmias, heart block, and myocardial infarction all have been reported with thyrotoxicosis. In one patient, ventricular fibrillation was precipitated by coronary artery spasm; both were eliminated after she become euthyroid.239 Although block has been described, facilitation of AV conduction appears more commonly in hyperthyroidism. In patients with hypothyroidism, AV block may be localized to both the AV node and His-Purkinje system and the myocardial action potential duration is prolonged.2N The Ventricle
Ventricular pacing is used to test the retrograde conduction system, to produce ischemia by prolonged pacing as described above, and to establish refractory periods and sequence of depolarization during tachycardias, as will be described below. Refractory Periods (Fig. 8) Several different refractory periods are defined by extrastimuli given with increasing prematurity until the stimulated tissue becomes unresponsive. Incremental or slow incremental ramp pacing also may be usedto estimate refractory periods, with the pacing rate increased until noncapture occurs. S 1Sl refers to the baseline spontaneous or paced cycle length and SlS2 is the interval from the last baseline beat to the premature extrastimulus (S2). In the atrium, SIS2S.. . may be designated A 1A2A . . . ; ventricular beats may be labeled VIV2V . . . , etc. By convention, refractory periods are generally measured with low pacemaker stimulation amplitudes, usually 2-4 times threshold. This convention will be assumedexcept where noted below, although reproducibility is enhanced if test stimuli are more than twice threshold.24’
ELECTROPHYSlOLOGlC
AV CONDUCTION Al ATRIUM
43
TESTING
!XiTEM
REFfUCTORY A3
Al
n
/\
PERKIDS
ERP
FRP
n -
ERP AVN
/\
n II
II
Ii1
Hl
FRP
II1
n III
Hz
H3
FRP AV Vl
Vl
V2
v3
FRP HIS-BB ERP Fig. 8. AV conduction system refractory periods: schematic (see text). Al. baseline atrial beet (spontaneous or paced); A2, programmed extrastimulus: A3, recovery beat. Hl, H2. H3, Vl , V2 and V3 are, respectively, His bundle end ventricular complexes following the appropriate atrial beat. ERP, effective refractory period: the longest SlS2 (here Al AZ) that does not conduct. In this illustration the alternative end virtually identical definition is used: the shortest Al Al resulting in conduction. FRP, functional refractory period: The shortest possible response to an SlS2 (here AlA2). At each level in the conduction system, the ERP may be considered as a stimulus-to-stimulus interval and the FRP es a response-to-response interval. As noted in the text. atrial refractory periods often include intraatrial conduction times, so that the ERP and FRP are identical only when stimulation end recording are performed at the same site, and there is no latency between stimulus and response.
The absolute refractory period is reached when SlS2 shortens to the point where S2 fails to evoke a responseno matter what the stimulus amplitude. The eaective refractory period (ERP) is usually measuredwith the stimulus at 2-4 times threshold, and is the longest SlS2 that does not produce a depolarization. For the atrium, the ERP may be measured directly from the SlS2 (AlA2). The ERP of the AV node is the longest AlA that does not give rise to a His bundle depolarization. The ERP of the total AV conduction system occurs when Al A2 fails to produce a V2. The ERP of a given bundle branch is the longest interval between two successive His bundle activations (SlS2 here, actually H 1H2) resulting in bundle branch block (see Fig. 8).
The functional refractory period (FRP) is the shortest possibleresponseto an SlS2. Thus, for a given site in the atrium, the FRP may be identical with the ERP unlessthere is a latent period between stimulus and response.Atria1 FRPs are often reported with high right atria1 stimulation and low atria1 response,so that ERP and FRP will differ. For the AV node, the FRP is the shortest interval between two His bundle depolarizations (HlH2) that could be produced by any SlS2 in the atrium (Fig. 8). Ultimately, the longest SlS2 that does not produce a response must virtually equal the shortest SlS2 that does produce a response. Some investigators therefore report the ERP as the shortest SlS2 resulting in a response. It is helpful to consider the ERP as a paced or tissue stimulus-to-stimulus measurement and the FRP as a response-to-responsemeasurement. Thus, the ERP of the AV node is defined in terms of atria1 stimulation, and the FRP of the AV node is defined in terms of the resultant His bundle depolarizations. The relative refractory period (RRP) is the longest SlS2 at which measurable conduction delay appears. For the AV node, this occurs when the A-H following S2 is longer than the A-H following Sl. Interpretation of refractory periods (Table Refractory periods are influenced by 51.2423243 many factors, thereby complicating the assessment of their significance. The refractory periodsof the AV node increasewith age to a greater extent than in other parts of the conduction system. Marked prolongations in the refractory period beyond the normal ranges may be observed but are not commonly used as a basis for a decision regarding permanent pacing. Analysis of refractory periods has helped in the understanding of reentrant arrhythmias, to be discussedlater. The Action Potential: Fast and Slow Responses (Fig. 9) A number of ionic channels have been identified and characterized in cardiac cells. These channels are said to be either “fast” or “slow” depending on the speed with which ions are transported, especially in depolarization of the cell. Compared to those using the fast channels, cells depolarizing via the slow channels have a
44
JOHN
Table
5.
Normal
Refractory
Periods
at Various
Cycle
Lengths’-
Adults
Children
ERP ” CL:
Longest
arsuring
Atrisl
FRP SD
+2s!3
n
Mean
(7 mo-
15 yrl
HIP SD
t2SD
n
FRP
Mea”
SD
+2sJ
n
Mean
SD
Captue+
Atrium A”
Mean
D. FISHER
node
7.6
236.
49
334
26
274.
47
366
40
167.
53
293
35
217‘
46
269.
44
377
406’ -
46
496
40
241*
56
353
15561
45 -
-
-
11
36 -
345. -
10
A96
5
412.
72
LB9
2
473
67
16071
-
-
9
323.
39
401
361
52
(4651
206
60
366
6
247
53
303
61 -
1465) -
6 -
427 -
74 -
-
-
CL: 650-600 Atrium
26
232
60
392
26
275
49
373
AV node
26
290
60
390
401 -
46
(525)
26 -
-
497 -
(552)
-
-
-
RBS
4
443
LB6
4
434
42 59
-
6 1 6
390 404
31
(466)
-
CL: 599-460 AtrWnl A”
node
30
232.
54
340
30
271.
49
369
37
199.
43
265
34
234.
43
30
326*
56
440
260.
55
370
10
365
35
435
37 -
354. -
66 -
365
423. -
520 -
37
26 -
406. -
57
367
29 -
61
(4921
-
RSB
6
LB6
CL:
-
6
370
459-260 Atrium
23
199.
26
255
23
252.
34
320
57
165.
37
239
54
200.
35
A”ti
16
260.
52
364
13
345.
27
399
55
219.
45
309
49
299.
46
RBB
4
16 -
13601 -
-
22
298
26
354
0
328 -
-
LB6
330
34
398
+Loneest
l
1
-
P < 0.05
CL assuin9 between
atrial adult
rspf~e: and
pediatric
696
t
107
for
adults,
535
+ 69
fa
-
12
children.
values.
less negative resting membrane potential, a lower amplitude of the action potential, a lower dV/dt resulting in markedly slower conduction velocity, and a longer refractory period. Phase 3 and 4 Blocks24”247 Phase 3 block (tachycardia-dependent block) occurs when an impulse arrives at tissues that are still in the refractory period. Phase 4 block (bradycardia-dependent block) occurs when the conduction of an impulse is blocked, for a variety of reasons, in tissues that are well beyond their refractory periods. The Gap Phenomenon244*24s-2s3(Fig. 10) During assessment of refractory periods using the atria1 extrastimulus technique, AV block may occur at a certain interval, but conduction may resume, after the gap, with further prematurity of the extrastimulus. There now appear to be at least six types of “gap” in AV conduction. For this discussion, Al is a beat of the basic atria1 cycle length. H 1 is the His potential resulting from an A 1. Dl is a distal Purkinje fiber or bundle branch depolarization resulting from H 1, and Vl is the ventricular depolarization resulting from Dl. These same letters followed by
number 2 are potentials in response to a premature atria1 beat. Each of the first three types of gaps occur at the H-V level, i.e., a His bundle potential is not followed by a ventricular depolarization. Type I gap. AV conduction is resumed because with increasing prematurity of A2 the A-H interval prolongs further so that Hl H2 now exceeds the refractory period of the His bundle and conduction resumes. Type II gap. Conduction resumes because increasing delay in the proximal His-Purkinje system results in a DlD2 exceeding the refractory period of the distal conducting system. Because the refractory periods in the distal conduction system are rarely symmetrical, conduction typically resumes with an aberrant QRS and a prolonged H-V interval. Type ZZZ gap. Conduction is resumed in spite of a shorter H 1H2 then was present at the time of block. Supernormal conduction, varying pulsatile vagal discharges, and a decrease in phase IV diastolic depolarizations have all been offered as possible explanations for type III gap, but the real mechanism or mechanisms remain a mystery. Type ZV, V, and W gap. These less
ELECTROPHYSIOLOGIC
TESTING
SLOW RESPONSE
FAST RESPONSE
-60 -8ON
1 @‘:uJih 1 ERP .a J-“(
l
A)
1 m+ . -
r::- - - - -- ,---A ------(WRESTING MEMBRANE) f Po&JLATED IAL (RflP) / ( PROTECTION ---I
FAST RESPONSE IMPULSE
ERP = EFFECTIVE REFRACTORY SNP = SUPERNORMAL PERIOD
PERIOD
SLOW RESPONSE
PROPAGATION
-CONDUCTION VELOCITY0.5 - 3 fl/SEC -SAFETY FACTOR (ABILITY TO -HIGH PROPAGATE TO NEXT CELL>
0.005
TO 0,1
!/SEC
Low
Fig. 9. The action potential: slow and fast response. See the text and references 71,256, and 257. The left-hand panel shows the fast response action potential characteristic of working myocardium and of Purkinje fibers, and the right-hand panel shows the slow response action potential seen in the sinus node, portions of the AV node, in diseased or altered working myocardium and Purkinje fibers. On reaching threshold, the upstroke of the action potential begins, moving the membrane potential from negative towards positive. The slope of this depolarization is expressed in terms of the change in voltage divided by the change in time and is directly proportional to conduction velocity within a given cardiac tissue. The dV/dt is considerably greater in fast response than in slow response cells. The fast response cells undergo a rapid, brief, and partial repolarization (phase 1). a relative plateau (phase 2). followed by repolarization with return to the resting membrane potential (phase 3). Slow response cells lack a phase 1. Following return to the resting membrane potential, the cell enters phase 4, generally equivalent to diastole, until the next depolarization. During phase 4, working myocardial cells maintain a constant membrane potential, but cells with pacemaker (automatic) activity gradually depolarize until the threshold potential is reached and another action potential is generated. In fast response cells, the effective refractory period (ERP) lasts until sometime during phase 3. In contrast, the effective refractory period of slow response cells may exceed the action potential duration. Other characteristics of the action potential are outlined in the illustration.
commonly encountered gaps have their initial blocks, respectively, at the distal AV node, the His-Purkinje system or AV node and the HisPurkinje system; the respective sites of proximal delay allowing resumption of conduction are in the proximal AV node, the atrium, and nowhere (supernormality). Interpretation and signijicance of the gap phenomenon. The gap phenomenon is not an abnormality but is primarily a reflection of the interplay between the conduction velocities and refractory periods of the different parts of the conducting system. Changes in neurohumoral influences or heart rate will, therefore, alter one’s ability to demonstrate the Gap Phenomenon in any given patient.“’ Gap phenomena in retrograde (V-A) conduction”’ and in intraatrial conduction2s2~2s3 analo-
gous to those seen in the antegrade conduction system have been described.
Supernormal conduction exists when a precisely timed beat results in restoration or improvement of conduction, especially in a previously depressed or blocked area. Supernormal excitability typically occurs just at the end of phase 3 of the action potential, and exists when there is excitation by stimuli that are subthreshold at any other point in the cardiac cycle. Clinically, supernormal excitability may be observed when a failing artificial pacemaker is able to capture only when its stimulus occurs at the end of the T wave. It is generally agreed that supernormality can occur in the HisPurkinje system, Bachman’s bundle in the dog,
46
JOHN
D. FISHER
GAP PHENOMENON HI
Dl “’
Late A2 z
I
aEarly A2 ~ (A-l/ Block)
I
0
A2
D?
Hz
A
I
AzHz
H+ti
)AlHt
@
))AIHI
(@
REASON FOR RESUMED CONDUCTION
A2
A A2
@GEE-: A
I
A
I
))))A1 HI ha
I
t AVN Delay :.tAzHz :. HlHz)H-RP t Proximal
III
A
I
A
A
)))AlHl
(0
y-7; Elay :.D& )RP ?Super Normal ?AVagal Tone ? i Phase 4 Block
Fig. 10. The gap phenomenon. Gap types I, II, and Ill in AV conduction are outlined (see text). Al, Hl , Dl, and Vl indicate, respectively, baseline atrial, His bundle, distal His-Purkinje system, and ventricular depolarizations. A2 represents an atrial premature beat with H2. D2, and V2 following when possible. In the top line, an atrial premature beat is conducted with a prolonged A2H2 interval. In the second line the A2 is followed by further prolongation of the A2H2 and subsequent block. In the third. fourth, and fifth lines, conduction is restored by further prematurity of A2 in the patterns of types I. II, and Ill gap. Explanations are provided in the key to the right of each line.
and probably in the working myocardium of the atrium and ventricle, but not in the AV node.
“slow response” not only make reentry possible, but are also related to an abnormal type of “triggered” automaticity.
Induction of Tachycardia
During the performance of electrophysiologic studies, incremental, ramp, or burst pacing, or programmed extrastimuli may result in the induction of tachycardias. The analysis and interpretation of such tachycardias is covered in the next section. TACHYCARDIAS
Mechanisms
of Tachycardias7’G256C257
An extensive critical review of the postulated mechanisms responsible for tachycardias is beyond the scope of this survey. Some of the basic tenets will be introduced briefly as background for subsequent discussions. Automaticity, conduction velocity, and the refractory period are prime determinants of the behavior of cardiac tissues. Tachycardias may be due either to an increase in automaticity or to a change in the relationship between conduction velocity and refractory periods that results in continuous propagation of an impulse, i.e., reentrant tachycardia. There are many variations on these themes, and phenomena related to the
Automaticity
Automaticity may be defined as spontaneous phase 4 depolarization ultimately reaching the threshold potential with generation of an action potential. The rate (frequency) will be increased if any of the following occur: a decrease in the action potential duration, an increase in the steepness of phase 4 depolarization, a less negative resting membrane potential, or a more negative threshold potential. Overdrive suppression.258S25g Upon cessation of rapid pacing or intrinsic rhythm from another site, an automatic focus will not return immediately to its baseline rate. Rather, there will be a pause followed by a gradual return to the baseline rate. Effect of premature beats on automatic rhythms. Suitably timed premature beats can
depolarize an automatic focus unless it is “protected” (see below) and, therefore, reset the timing of the automatic focus. Premature beats have inconsequential effects on the intrinsic rate of firing of automatic foci. Overdrive excitation.258 Purkinje cells stud-
ELECTROPHYSIOLOGIC
47
TESTING
ied in vitro and subjected to catecholamines may exhibit excitation or acceleration rather than suppression following overdrive pacing. Relatively slow pacing may be followed by extrasystoles or minimally accelerated automatic firing. Faster pacing for brief periods may result in automatic rhythms that are slower, similar to, or even faster than the paced rate. Prolonged pacing of such tissues, however, generally results in overdrive suppression. The role played by this mechanism in clinical arrhythmias is not yet defined. Triggered automaticity.259~260 Slow response cells may have one or more oscillatory afterpotentials following repolarization. The amplitude of the afterpotential may be increased by catecholamines and by pacing or premature beats. The afterpotential may reach the threshold for activation, and the ensuing action potential may be followed by an afterpotential, which itself reaches the threshold for activation initiating a sustained accelerated rhythm. Sustained rhythmic activity can also be terminated by a premature beat. Protection and entry block.256s26’*262 Automatic rhythms may continue to depolarize with the timing unaffected by spontaneous or induced beats from other sites. At least six mechanisms have been proposed to explain such protection: (1) a very rapid rate (short cycle length would render the focus almost continuously refractory); (2) the threshold potential of the parasystolic focus might be so high (less negative) that impulses from the surrounding tissue would be unable to bring it to threshold; (3) the refractory period of the parasystolic focus might be so long as to occupy much of diastole; (4) phase 4 depolarization of cells surrounding the parasystolic focus; (5) a protection potential has been proposed262 that is a variant on the theme of phase 4 block-when a cell depolarizes to its protection potential during phase 4 it may continue its spontaneous depolarization to reach threshold, but is impervious to external stimuli; and (6) unidirectional block as commonly observed in reentrant tachycardias (see below).
During normal rhythm the heart is sequentially activated by an advancing wavefront of depolarization that is extinguished when all accessible areas of the myocardium have been
depolarized. The heart then awaits the next impulse from the sinus node. Reentry occurs when an impulse, instead of being extinguished, contrives to exist in a cardiac backwater for a period sufficient to allow the rest of the myocardium to repolarize, at which point the persisting impulse reenters the myocardium, depolarizing it. The depressed area harboring the impulse that is to reenter the remaining myocardium is usually populated by slow response cells capable of slow conduction and may occur in areas surrounding fibrosis or infarction in atria1 or ventricular tissues, especially subendocardial Purkinje fibers, as well as in the sinoatrial and atrioventricular nodes. Two conditions, therefore, are required for reentry to occur: (1) unidirectional block, and (2) an area of slow conduction so that the impulse can survive until the cells in front of it are no longer refractory. Because refractory periods shorten with decrease in cycle length and conduction velocities decrease when depolarization occurs during the relative refractory period, two or three critically timed premature beats may be required to adjust the conduction velocities and refractory periods so that termination of a reentrant tachycardia occurs. Summation.7’~256 Summation occurs when the combined effects of two impulses result in conduction through tissues that could not be excited by either impulse individually. Impulses that might require summation for propagation because of a low safety factor for conduction are characteristic of slow response cells and may occur in the AV node and in depressed areas elsewhere in the heart. Anatomical arrangements that permit summation of impulses in one direction, but not the other, in effect create unidirectional block, which is one of the cornerstones of reentry. Overview on Tachycardia
Mechanisms
A few years ago it was thought that clinically useful tests existed that could separate reentrant from automatic tachycardias. Reentry tachycardias were thought to be characterized by reproducible initiation and termination by critically timed programmed extrasystoles (PES). PES that did not terminate the tachycardia often resulted in a pause that was less than compensatory, presumably because the reentrant circuit had been entered by the premature beat. This
40
JOHN
last criteria for reentry was the first to go. Premature beats during normal sinus rhythm also result in pauses that are less than compensatory. With the identification of triggered automaticity initiated and terminated by PES, each of the classic criteria for the electrophysiologic diagnosis of reentry thus have been found compatible with automaticity. The clinical cardiologist, therefore, is unable to state with certainty whether most tachycardias are due to reentry or to automaticity, especially of the triggered type. Nevertheless, most workers subscribe to the convention defining reentrant arrhythmias as those that can be initiated and terminated reproducibly by programmed extrastimuli in a well defined zone. Electrophysiologic Techniques
Study
of Tachycardias:
Techniques used in the study of tachycardias are the same as used in studies of the impulse formation and conduction system. These include programmed extrastimuli, rapid pacing, physical maneuvers including exercise and carotid sinus massage,pharmacologic agents, and psychologic stresses. In general, a well done electrophysiologic study will include programmed stimulation and incremental or ramp pacing from several sites in the atrium and the ventricle. When the endocardial recording sites are carefully chosen, these techniques will provide the bulk of the data required for accurate analysis of both the conduction system and tachycardias. Pharmacologic Agents Regrettably, it is not yet possible to select an effective treatment for every patient basedsolely on knowledge of the mechanism of the tachycardia. Characteristic responses to some drugs, however, may permit a more definitive diagnosis of the mechanismof a given tachycardia. Candidatesfor Electrophysiologic Studies of Tachycardias Studies performed specifically to aid in the therapy of the patient are appropriate when tachycardias are frequent, life-threatening, recurrent, unresponsive to conventional drug therapy, or are a psychologic burden to the patient.
D. FISHER
The technique of serial electrophysiologic testing is an efficient means of establishing the most effective pharmacologic or pacemaker therapy (seelater section). Electrophysiologic studies are also useful both during and in laying the groundwork for antitachycardia surgery. Electrophysiologic testing is beginning to play an important role in the identification and treatment of patients at risk of sudden death. Mappin?’ “Mapping” is the useof recordings or stimulation at a sufficiently large number of sites to permit accurate localization of initial and/or sequential depolarization. Epicardial mapping during tachycardia. At the time of open heart surgery, the time of depolarization at each of a large number of sites is determined and compared to a reference lead. Epicardial mapping has proven useful in localizing tachycardias with initial depolarization in the free wall of the atrium or ventricle. With atria1 pacing, epicardial mapping also can reveal the site of early ventricular activation by an anomalous atrioventricular pathway such as a Kent bundle. The technique is not without its limitations: 264the site of epicardial activation may be several centimeters distant from an actual endocardial focus; epicardial mapping cannot localize accurately tachycardias originating in the septum. The epicardial surface usually can be mapped in approximately 10-l 5 min by experienced personnel using a mobile hand-held probe. The use of a “sock” pulled over the heart with many built-in leads that can record simultaneously, allows computer-assisted mapping of a single beat.265 Endocardial mapping (passive observation from multiple sites).266 During electrophysiologic studies, some insight into the depolarization sequence can be gleaned from stationary well sited leads. More precise information requires a mobile catheter lead. At the time of open heart surgery, endocardial mapping can be done more precisely and permits localization of arrhythmias arising in the endocardium or the septum. Pace mapping (active stimulation from multiple sites).267 Epicardial or endocardial pacing can mimick the QRS configuration of a tachycardia if the stimuli are delivered close to the
ELECTROPHYSIOLOGIC
49
TESTING
focus or point of earliest activation. Changes in pacing site change the QRS configuration, and preliminary surgical experience confirms that good localization of the tachycardia is possible using pace mapping. The ultimate role of this technique is not yet defined. Electrophysiologic Tachycardias
Characteristics
of Specific
Supraventricular Tachycardias (Table 6, Figs. 11 andI2) Definitions and general considerations. The term “paroxysmal atria1 tachycardia” (PAT) generally has fallen out of favor, being replaced by the lessspecific term paroxysmal supraventricular tachycardia (PSVT). Included within the scopeof PSVT is a constellation of arrhythmias within which true atria1 tachycardia plays a
“SVT”
relatively small role. More commonly, PSVT results from abnormalities in the AV node, one of the overt or concealed preexcitation syndromes, or even to abnormalities of the sinus node. Several factors are considered in the differential diagnosis of PSVT. (Many of these will be discussedfurther in the context of specific tachycardias.) (1) Response to programmed extrastimuli: reproducible initiation and termination of the tachycardia by programmed extrastimuli within well defined tachycardia initiation and termination zones suggests the clinical diagnosis of a reentry mechanism in spite of awarenessof the existence of triggered automaticity. (2) Additional responses to pacing or programmed stimuli: this is observed if the ECG
TYPES
Fig. 11. Types of supraventricular tachycardia (see text). “Circuit diagrams” outlining the mechanisms of tachycardia. During tachycardia, strategic placement of recording electrodes would allow sequential mapping of depolarizetion, which, in many cases, would be sufficient to identify the type of tachycardia. Abbreviations (see text): AAT, automatic atrial tachycardia; AcAVNT, accessory AV nodal tachycardia: AFL, atrial flutter; AN-JT junctional tachycardia arising at the AN region of the AV junction; AVNCT, AV nodal conduction tachycardia; AVNRT, AV nodal reentrant tachycardia; Cone WPW, concealed WPW syndrome; CNPSNT, chronic non-paroxysmal sinus node tachycardia; HBT, His bundle tachycardia: James, tachycardia related to en atrial-His bypass tract; LGL. Lawn-Ganong-Levine syndrome; Mahaim. tachycardias related to nodal-ventricular, or fasciculoventricular fibers: NH-JT. junctional tachycerdia arising at the NH region of the AV junction: NSR, normal sinus rhythm: “PAT,” paroxysmal trial tachycardia; SANRT. sinoatrial nodal reentrant tachycardia; WPW, Wolff-Parkinson-White syndrome; RA, right atrium: RV. right ventricle; LA, left atrium: LV, left ventricle.
50
JOHN
Table
6.
Typical
Findings
Characterizing
SANRT
ECG
h
SVTI
Pas
NSR: often
Types
CNPSNT
rate
wide
R-P
duration
Brief
LOIt
Across
Facing
AAT
P-variable
range
Pages)
Flutt0l
P-variable
AVNRT
“Sawtooth”
aften
Ps
AVNCT
P in or neaf
COmlllO”
ClRS.
‘k of R-R
beyond Epcxde
(Reed
PAT
Ps 8% NSR;
rate slow
of SVT
D. FISHER
often
P nnvarted
rreg.
PwNSR
m II, 111, AVF
Varies
Parox
w
Varies
Par01
a
“pftrm”
Varies
-perId Induce
and
terminate
WlIh
PES
Yes
NO
YES
Unusual
Rare
Yes
7
Whh
b”rst/wer#w
YeS
NOhare
Yes
Un”S”fil
Yes
Yes
7
Effect
of BBB
Effect
of wagal
on rate tone
None
Nom
Marked
same
NCWld
NCSllM,
cases
slow
None
NOW
NOW
None
NOW
VWiS
LIttIe
Little--may
Significant
?
NWlTld
Normal
NO,lW
cause A-H
curve
with
At.
pace
or PES
AVB “Break”
due
dual V-A
curve
with
V-pace
(x PES
NO,ltld
NWIW
NCSKd
Normal
NCNltld
“Break”
due
dual 1:t
AVratio
Atrlal
*
d+olarization
wth
seq”mc*
as NSR/normal
as NSRlnwmal
varies
tachylV-stim
among
Rare
“S”d
Varies
Complex
HBE
to
“srealr”
to
V-A
paths block
paths 1:2AV. area
first
etc.
as NSR/namal
indiwduals
H-V in NSR
NGiltMl
NLVltXll
NCSllld
Normal
Normal
Normal
N-Xltld
I” ,ach
Namd
NO,ld
NWTIA
NOrI
NWttMl
NDrlM
NLTl3l~l
NO
NO
NO
NO
NO
NCI
NO
Normal
Normal
NC#llMl
NCXmd
Atrium
peexcited
when ECG
His
by VPES
refractay
(in NW
Nwmal
COmlll*“tS
SNRT.
Nwmal SACT
usually Effectwe
Rx*
Asrociated
2 groups:
nwma,
responds
dseease
Most to P D.Q
NO
NO
f- Normal
PR
common
PSVl
P
0.V hsin
1
pacing
P,DPH
Yes
YES. esp.
pacing.
DC
be
text1
CV
P.D.PA.0
7
+
7
cnikken AAT.
automatic
tachycadia; length;
atria,
AVNRT. HgE.
progammed *Effective
low
tachycadia:
AV right
node
atrium
extrastim”Ii;
0.
treatment.
Drugs
AcAVNT, reentry
tachycad+a;
recaded
on His
quinidine; listed
accessay
bundle
currently
bundle
node
tzxhycardia:
branch
ektrogam;
v. verapatti,: are
AV
BBS,
a
block:
Kent,
V-A
ewe.
plot
soon
to be available
Kent
ventricle
AN,NHT,
tachycardia
CNPSNT.
chronic
bundle:
D. digitalis:
to atrium
in USA.
See
at atriwvxlal ncqxroxysmal DC CV.
conduction text
complex during pacing at the same rate as the tachycardia is similar and there are changes with alterations in the pacing site. Of particular importance is the shape of the A-H curve with increasing heart rate. In contrast to the normal gradual increase in A-H interval with increasing heart rate or prematurity of the programmed extrastimulus, characteristic changes occur with supraventricular tachycardias involving the AV conduction system (Fig. 12). (3) The site of origin and sequence of atria1 activation: it is unlikely that the sinus node is responsible for a tachycardia with initial depolarization in the distal reaches of the left atrium. (4) Important clues from the ECG:268 (A) AV nodal reentrant tachycardia is suggested by simultaneous atria1 and ventricular activation. (B) Inverted P waves in the inferior leads and an R-P interval less than one-half the R-R interval occur in 30% of patients with AV nodal reentrant tachycardias and in virtually all patients
and
time Table
1 fw
or nodal-His sm”s
DC vs.
node
cardioversion; ventric”,ar
other
~“nctons: tachywxdia; DPH.
stimulation
AVN. A-H
phenytain; cycle
AV
cuw.
node: plot
P. propranalol;
AVNCT. A-H
vs. PA,
AV atrial
node
conduction
sttm”Iation
procame
amide;
cycle PES.
length.
drugs.
with a retrogradely conducting bypass tract. (C) Atypical, often incessant, AV nodal reentry often features retrograde P waves with long R-P intervals. (D) The ratio of atrioventricular complexes: AV nodal reentrant tachycardias need not involve the atrium or ventricle, so that a 1:l relationship need not exist. Sinus or intraatria1 tachycardias may be accompanied by AV block. PSVT involving Kent bundle type of bypass tracts in the circuit always have a 1:l AV Kent bundle is ratio. (E) An ipsilateral suggested if the rate of a tachycardia slows during the presence of bundle branch block. Bundle branch block is more common in tachycardias involving a Kent bundle than in AV nodal tachycardias. (5) Physiologic maneuvers including carotid sinus massage, exercise, or physical tilting of the patient may result in autonomic and blood pressure changes that can affect a tachycardia. (6) Pharmacologic interventions using medi-
ELECTROPHYSIOLOGIC
51
TESTING
Table
Junctional
6.
(Continued)
AVN
Tachycxdias Concealed
ACAVNT
AN.NHT var
P-P.
WPW
HST
Enhanced
BYpaSS
WPW
AVN
IJames)
Maham
P
nnwtted
Normal
CT wide
in
II.III,AVF Parox
M non-
parox
t Slow
if 1p511
NO
Yes
NO
Yes
7 Yes
None
Slows
Yes Yes
if tpsdat.
s,ows
to Kent Significant
Vawable
Normal
a break
with
Norma,
or break
area
dseWhe(B AV
a Rat
Flat.
Flat
* Flat
Nwmal
+
+
C”,W
Namal
HBE
Variable Flat
delta
hrrt
or
rings
IAV
first
Kent
Antidramic:
near
HEE
Namaljshmt
Short
Namallshart
Normal
occ.
break
flat)
Olthadramic:
*bang
if ips,,.
to Kent
near
+
Fwst
near
HSE
Fmt
nex ““less
Inor
HBE Kent
Nwmal
Nwmal
NCW”A
Normal
Shortlnarmal
NO
No (unless
Shortlnwmal
medromicl NO
NO
Yes
Kent
NO
normal
Short
present) + Normal
+ Normal
Short.
P-R.
nwma,
ORS
Short
P-R,
ClftS May
be due
digitalis
to fox
D may rate
cause wth
rap,*
common
““common
A-F
VI
associated
really conc*aied 7P.D.”
PDPH
NO
Often
tIPA,
+ D.P
(AVNI
children
NO
cations that are fairly specific for affecting conduction and rhythmicity in individual portions of the heart may help in the diagnosis of some tachycardias. Sinus Node Tachycardia
A5 fa
(Figs. 11 and 12)
Sinus node reentrant tachycardia (SNRT)269-27’ is usually paroxysmal and often unsustained. The rate is moderate, typically below 150 and at times below 100 bpm. The mechanism of this tachycardia is assumed to be reentry within the perisinus nodal tissues. The conftguration of the high right atria1 depolarization may be different during tachycardia than during sinus rhythm, and following the termination of the arrhythmia, the configuration may not return immediately to its baseline state, perhaps because of refractoriness of those perinodal fibers involving the tachycardia. Chronic nonparoxysmal (automatic) sinus node tachycardia (CNPSNT) (Figs. 11 and 12) occurs due to increased automaticity of the sinus node in the absence of underlying diseases such
WPW
t PA.0
= normal
P-R:
Comma”
Speculation
D.P.V
PA.a
d&a only
SVT:
AVNRT
a WPW
N”
as thyrotoxicosis.*‘* The rate may range up to 200 bpm, but averages about 130. There are two variants: one group is propranolol responsive, suggesting that the mechanism may be inappropriate sympathetic tone. There is no association with the more generalized autonomic nervous system dysfunction syndromes.
Reentrant Atria1 Tachycardia (Figs. I1 and 12)
(PAT)27Q~27’~273-275
Reentrant atria1 tachycardia (“true paroxysmal atria1 tachycardia” or PAT) usually occurs in the setting of clinical heart disease. The rate and ECG appearance are variable. This rhythm may be either macro- or micro-reentrant. It may arise at any point in either atrium, perhaps involving specialized tracts in some instances.275 The atria1 waves may assume virtually any configuration on the ECG. “Pace mapping” from 12 atria1 sites in 69 patients resulted in diagnostically useful patterns only with left atria1 pacing near the left pulmonary veins (neg-
52
JOHN
JORMAL SANT AT
D. FISHER
IUAL AVN PATHS
A-H /
t
H-V s
QRS t
RAT7 WPW
I1&L
Fig. 12. Differential diagnosis of supraventricular tachycardia. Characteristic changes in the A-H, H-V, and QRS intervals are graphed on the ordinate as a function of increasing heart rate. which is displayed on the abscissa. SANT, sinoatrial nodal tachycardia. AT, intraatrial tachycardia. LGL. Lown-GanongLevine syndrome. WPW. Wolff-Parkinson-White syndrome.
A-H f H-V g
QRS t
RATF
ative P in lead 1) or inferior veins and coronary sinus (positive bifid P in V1).276 Automatic Atrial Tachycardia (Figs. 11 and 12)
fAAT}27’*278
The electrocardiographic presentation and the endocardial depolarization sequence of AAT are similar to those of reentrant atria1 tachycardia. Many patients with this arrhythmia have underlying heart disease, and it may be proportionately more common among children than among adults. The arrhythmia may be paroxysmal, but “permanent” atria1 tachycardia also occurs. The differential from other tachycardias is similar to that for reentrant atria1 tachycardias except that induction by programmed stimulation is rare. Atria1 tachycardia may occur as an escape mechanism after a sinus pause. In such cases, tachycardia following programmed atria1 extrastimuli (A2) does not occur immedi-
ately but only following a long equivalent to the sinus pause. affects the tachycardia but may treatment of heart failure tachycardia. Vagally Mediated Atria1 FIutter279
A2A3 interval Digoxin rarely be needed for in persistent
Atria1 Fibrillation
and
Vagal stimulation can convert atria1 flutter into fibrillation probably because of a shortening of the atria1 refractory period. Patients with the syndrome of vagally induced atria1 arrhythmias usually have hearts that are otherwise normal. Attacks of fibrillation or flutter are characteristically paroxysmal, and the essential feature is their occurrence at night or at rest rather than during daytime or exercise or emotional stress. Most episodes are preceded by progressive slowing of the heart rate, followed by relatively late premature beats (coupling interval greater than
ELECTROPHYSlOLOGlC
53
TESTING
350 msec), and ultimately by atria1 fibrillation or flutter. The most effective therapy has been directed at increasing the heart rate or prolonging the refractory period. Atropine, disopyramide in large doses, and particularly amiodarone are effective in this condition. Verapamil is generally of little use and digitalis and propranolol may worsen the condition. The most effective long-term therapy appears to be atria1 pacing at rates of 80 or more. Vagally mediated atria1 fibrillation or flutter should be considered in patients whose rhythms are said to be “drug resistant.” Atria1 Flutter2” Atria1 flutter is a regular intraatrial tachycardia with a rate usually in excess of 240 bpm. There is evidence to support both reentry and automaticity as the cause of flutter; but their role is unclear in the two types of atria1 flutter observed in both animal and human studies. Type 1 flutter is the classic type with “sawtooth” atria1 waves visible on the ECG, especially in the inferior leads and VI where the deflection is more negative than positive. The atria1 rate ranges from 240 to 340 bpm. Animal studies suggest an origin in the right atrium between the superior and inferior vena cava with a complex reentrant pathway responsible for the sawtooth configuration of the flutter waves. Type I flutter is subject to an “entrainment” phenomenon,2s’ which serves as a guide to the minimum rate of pacing required for termination with the least likelihood of induction of atria1 fibrillation, Allowing for changes in configuration due to the pacing stimulus, the flutter pattern initially is unchanged in its ECG morphology as the pacing rate increases, i.e., the arrhythmia appears to be pulled along or “entrained” by pacing. At a critical rate, the atrial complex will change in shape, and if pacing is stopped at this point, reversion to normal sinus rhythm usually occurs (see article by Waldo et al. also in this Symposium). Type II flutter is more rapid than type 1, ranging from 340 to 430 bpm, and on the surface leads often is represented by small positive deflections in the inferior leads and VI. Animal studies suggest that the apparent isoelectric baseline is not due to the absence of atria1
activity, but to the presence of concurrent opposing wavefronts. Earliest activation appears to be in the right atria1 margin at the junction between the right atria1 appendage and body of the right atrium. In contrast to type I flutter, type II virtually is impossible to terminate using pacing techniques, and treatment must be empirical. In some patients type II flutter may be difficult to distinguish from type I atria1 fibrillation. A V Nodal Reentrant Tachycardia (A VNR T)282-29’(Figs. 1 I and 12) AV nodal reentrant tachycardia may occur in paroxysmal or “permanent” forms. The mechanism ultimately is related to the presence of two or more pathways in the AV node that permit the establishment of a reentrant circuit. Usually the antegrade pathway during a paroxysmal tachycardia has a slower conduction velocity than the retrograde pathway (slow-fast form), but a fast-slow form also occurs. Clinically, patients afflicted with AV nodal reentry tachycardia may or may not have otherwise healthy hearts. The tachycardia rate is typically between 150 and 200 bpm but may occasionally be slower or faster. There are no typical changes in the QRS complex during normal sinus rhythm, and the P-R interval is of normal duration. During tachycardia there are no additional changes in the QRS complex unless there is a rate-related aberrancy. On the ECG, atria1 depolarization is commonly obscured when it is simultaneous with ventricular depolarization. The V-A (R-P) interval tends to be less than half the R-R interval in those cases where atria1 depolarization is visible; longer R-P intervals in AV nodal tachycardias are associated with atypical and resistant variants.268 A retrograde P prior to the QRS may be seen with the “fast-slow” variant. Electrophysiologic studies. The hallmark of AV nodal reentrant tachycardia is the identification of two or more AV nodal pathways and the induction of a tachycardia that can be shown to depend on these pathways. Dual A V node pathways. Incremental atria1 pacing normally results in a gradual increase in the A-H interval with increasing heart rates until the refractory period of the A-V node is reached. In patients with the common form of dual A-V nodal pathway, there is a break in the
54
curve such that at a given pacing rate the A-H interval will suddenly shift from a lower to a higher value. Dual pathways cannot always be identified during atria1 pacing or PES, either because of unidirectional conduction properties or because the faster pathway may have a shorter refractory period during antegrade conduction than the slow pathway.287-28g Ventricular of His bundle pacing or PES may reveal a break in the curve of the V (or H) to A interval with shorter cycle lengths. Alterations in refractoriness by agents such as atropinezs5 or procainamide286 may be required to achieve the balance of conduction velocities and refractory periods necessary to reveal the presence of dual pathways or to induce a tachycardia. Dual AV node pathways sometimes are identified in patients without a clinical history of paroxysmal supraventricular tachycardia, especially children.283 Determinants of AV nodal reentry. A low risk for development of paroxysmal tachycardia is suggested by absence of a history of tachycardia, absence of echo beats in response to atria1 premature stimulation, and lack of VA conduction during ventricular pacing.*‘* Neither the atrium nor the ventricle are vital to this tachycardia because the circuit is entirely within the AV node.284 Hence, AV nodal reentrant tachycardia may exist without regard to AV ratio. If there is biock in retrograde conduction from the AV node to the atrium, a situation may exist in which a supraventricular tachycardia (AV nodal) is present even though the ventricular rate is faster than the atria1 rate.284 Incessant or permanent form of A V nodal In addition to the reentrant tachycardia.28g-2g’ more common paroxysmal form of AV nodal reentrant tachycardia, there is another, more incessant, variety that is relatively more frequent in children. In contrast to the paroxysmal variant, antegrade conduction is usually by the faster pathway and retrograde conduction by the slower (fast-slow form). On the peripheral cardiogram, the onset of a tachycardia is heralded by an inverted P wave, which appears to conduct with a shorter P-R interval than did the sinus rhythm. During tachycardia, retrograde P waves precede the QRS. Although the fast-slow form can occur with paroxysmal AV nodal tachycardia, the slow-fast variety is more common, and results in a P wave that is either simultaneous with the QRS or follows it. The
JOHN
D. FISHER
“incessant” form actually is easy to stop temporarily with pacing techniques, and may even stop spontaneously, only to restart within a few beats. In paroxysmal AV nodal tachycardias, an atria1 premature beat results not only in block in the faster pathway, but in additional slowing of conduction in the slower pathway. With the permanent type of tachycardia, a premature beat is not required. The slow pathway is already sufficiently slow to allow reentry provided that unidirectional block occurs. Drug therapy often is unrewarding in patients with the incessant form of tachycardia, and pacemaker therapy, when successful, often involves the use of nonstandard sophisticated devices.2g’ Diferential diagnosis (Fig. 13). AV nodal reentrant tachycardia must be differentiated from other forms of PSVT. Sinus node and intraatrial tachycardias, and those due to lateral anomalous atrioventricular connections (Kent bundles), can be eliminated on the basis of depolarization sequence. Responses to measures that affect the AV node rather than the HisPurkinje system (e.g., carotid sinus massage, digitalis) help differentiate such a tachycardia from a His bundle tachycardia with retrograde block. The possibility of a retrogradely conducting concealed Kent bundle entering the atrium very near the AV node also must be considered. During ventricular pacing, such a septal Kent bundle conducts to the atrium with little increase in the V-A interval with increasing pacing rates, in contrast to the prolongation to be expected if conduction is via the AV node. Enhanced AV
ON 1258 Fig. 13. Anomalous AV connections. K. Kent bundle; J. James fibers: atrio-Hisian; atriofascicular; Erechenmacher fibers; M, Mahaim fibers: nodoventricular: fasciculoventriculer: AVN, AV node; BH, bundle of His. (See text.) Reproduced from Narula= by permission of the author and the American Heart Association.
ELECTROPHYSIOLOGIC
55
TESTING
nodal conduction may exist and mimicks the effects of a septal Kent bundle. Enhanced AV nodes, however, still respond typically to vagal maneuvers, parasympathetic drugs, and beta blockers, causing a prolongation in conduction not to be expected with an anomalous pathway. A ventricular extrastimuli, given just after the inscription of the His bundle deflection (i.e., when the His bundle is refractory), can be conducted back to the atrium only in the presence of an anomalous pathway. Demonstration of retroconduction during the refractory period of the His bundle may require the presence of a tachycardia. The retrograde equivalent to the Lown-Ganong-Levine syndrome in which an atrio-His bypass is presumed to exist would be suspected if V-A conduction were impossible during the refractory period of the His bundle, and if V-A conduction, when present, failed to respond to parasympathetic maneuvers. Nonreentrant Tachycardia Due to Simultaneous Conduction in Dual AV Node Pathways (AV Node Conduction Tachycardia. AVNCT)292 (Fig, 11) Rarely, conduction velocities will differ so markedly in the fast and slow pathways that impulses from each will be conducted to the ventricle. Thus, a single sinus beat results in two ventricular depolarizations. Depending on the relative conduction velocities, the peripheral ECG might reveal a regular SVT with the ventricular rate double that of the sinus rate or bigeminal rhythm, possibly with rate-related aberrancy of the second beat mimicking fixed coupled ventricular premature beats. In the patients studied, slow pathway conduction was permanent, and periodic block in the fast pathway resulted in varying degrees of block imitating a junctional rhythm with premature beats, or even atria1 fibrillation with a premature ventricular complexes. Arrhythmias due to this mechanism would depend on the absence of AV nodal echo beats. Automatic (Fig. 1)
Junctional
Tachycardia
(JT)293
These arrhythmias presumably arise in the AN and NH regions of the AV node and in the His bundle and may cause paroxysmal or nonparoxysmal junctional tachycardias (NPJT).
Atria1 pacing at rates faster than the tachycardia may result in 1:l conduction to the ventricles, but fails to suppress the ectopic focus. Atria1 and ventricular premature beats and pacing also are unable to initiate or terminate the tachycardia. Direct current cardioversion also fails, suggesting an automatic mechanism. In these patients, digoxin is useful for the treatment of congestive heart failure, but does not alter the tachycardia. Propranolol, reserpine, phenytoin, and chlorpromazine may be of some use. Quinidine and lidocaine appear to be ineffective. Digitalis toxicity may cause “PAT with block,” actually a form of atria1 or JT due to intraatrial or AN area reentry or automaticity. His Bundle Tachycardias
(HBT)2g3 (Fig. 1)
Tachycardias originating in the His bundle result in a narrow QRS complex unless raterelated aberrancy is present. Atrioventricular relationships will be determined by the retrograde conduction properties of the AV node. The H-V interval may be shorter than during sinus rhythm. Some of the automatic junctional tachycardias described above are His bundle tachycardias. Both reentry and automaticity can occur in the His Purkinje system and more will be said about such arrhythmias in the section on ventricular tachycardias. Tachycardias (AcAVNT)*~~
Related to Accessory (Fig. 11)
A V Nodes
Incremental pacing, antegrade or retrograde across the AV node, results in a steady increase in the A-H or H-A interval. Patients with dual or accessory A-V nodes, with slightly different conduction properties, act functionally as though they had two separate A-V node pathways. Electrophysiologic studies in this condition reveal evidence of this separation (as occurs in the Wolff-Parkinson-White Syndrome) with both pathways having A-V node-like properties including prolongation of conduction time with incremental pacing, and responsiveness to vagal tone, digitalis or propranolol. Tachycardias Connections: (Figs. 11-14)
Due to Anomalous AV Preexcitation Syndromeszs5~zs”
Preexcitation exists when conduction between the atrium and the ventricle occurs earlier than
56
JOHN
expected, often by a route other than the normal atrioventricular conducting system of the AV, His bundle, and bundle branches. Preexcitation may occur in either the ventricle or the atrium and may be overt or concealed. Tachycardias in neonates may be enhanced by predominant cholinergic innervation and may subside after several months with changes in autonomic tone, and as the natural process of fibrosis in the maturing heart ablates the anomalous pathway.297 The Wolff-Parkinson-White syndrome in older children is similar to that found in adults. 298In some patients, the presence of anomalous AV connections is unmasked after damage to the normal conduction system, e.g., following acute myocardial infarction.299 Wolff-ParkinsonSyndrome)
White Syndrome
(WP W
The hallmark of this most classic of preexcitation syndromes is the presence, during normal sinus rhythm, of a “delta” wave on the peripheral electrocardiogram. The delta wave occurs at the beginning of the QRS complex after an unexpectedly short P-R interval and represents preexcitation of the ventricle by anomalous conduction over a Kent bundle. The QRS complex is a fusion of ventricular depolarization caused by a Kent bundle that lies entirely outside of the normal atrioventricular conduction system and of depolarization following conduction through the normal system. The Kent bundle does not have the delaying properties of the normal AV node, accounting for the preexcitation of the ventricle. Amplitude and axis of the delta wave depend on the location of the Kent bundle, the relative time of arrival of a sinus impulse at the AV node and the anomalous pathway; the actual conduction velocity through the Kent bundle; and the degree of delay encountered by the wavefront in passing to the normal atrioventricular conduction system. The delta wave may be absent if the AV node conducts rapidly and the anomalous pathway is far lateral on the left (Fig. 14). Classification of Wolff-ParkinsonWhite synIt was previously customary to divide dromes. Wolff-Parkinson-White syndrome into type A and type B. Type A is characterized by an upright delta wave in lead VI often resulting in a right bundle branch block like configuration, and generally represents a left-sided bypass
D. FISHER
tract. Type B is characterized by negative delta wave in V 1, mimicking an anterior wall myocardial infarction or a left bundle branch block and generally occurs with right-sided Kent bundles. Detailed mapping studies have shown that Kent bundles may exist almost anywhere around the atrioventricular valve rings, and a more complicated classification system has proved necessary. Kent bundles are now described as right or left posterior, lateral, or anterior, and right or left anterior or posterior paraseptal. WP W-related tachycardias. This syndrome is the archetype of the macroreentry tachycardia. During tachycardia, antegrade conduction is usually via the normal atrioventricular conduction system (orthodromic) with retrograde conduction through the Kent bundle resulting in a tachycardia with a narrow QRS complex. This often is termed a supraventricular tachycardia but the mechanism is actually an atrioventricular macroreentry circuit. Since conduction proceeds from ventricle to atrium, the atria1 depolarization follows the QRS complex rather than being concurrent as occurs with some AV nodal tachycardias. The presence of an inverted P wave in lead I during tachycardia strongly suggests the presence of a left-sided Kent bundle, but intraatrial tachycardia originating in the left atrium will occasionally be encountered. Less commonly, antegrade conduction occurs over the Kent bundle (antidromic conduction), creating a wide QRS simulating ventricular tachycardia; retrograde conduction then occurs via the normal pathway. Intermittent bundle branch block. Aberrant conduction due to a rate-related bundle branch block may occur and can provide diagnostic challenges as well as insights. As with aberrantly conducted supraventricular tachycardia, the rhythm must be distinguished from ventricular tachycardia. Of diagnostic interest, bundle branch block occurring on the same side as a Kent bundle will result in a lengthening of the cycle length of the tachycardia (a slowing of the rate) because the ventricular portion of the circuit will take longer to complete in the presence of ipsilateral bundle branch block. Antegrade (antidromic) conduction through a Kent bundle occurs less commonly than retrograde, but if present, again must be distinguished from ventricular tachycardia. With antegrade conduction through the Kent bundle,
ELECTROPHYSIOLOGIC
57
TESTING
l
0 khoii
Trad
Conduction
E
Bundle NSR
Jomos NSR
of Kant
Conduction I
and
Kant
Fibror
C James NSR
Tract CowhAon I
F Jomor NSR
ond
Yahaim
Fibns
A
AP
*-+
w
l-2 J-6 Fig. 14. Effects of atrial pacing types and combinations of anomalous and the American Heart Association.
on conduction intervals and the AV connections. Modified from (See Figs. 10 and 12 and text.)
retrograde conduction is relatively slow as it occurs via the AV node, and the V-A interval is generally longer than encountered with retrograde conduction through the Kent. Enhanced AV node conduction commonly occurs in WPW patients, however, so that retrograde AV node conduction may be rapid. Electrophysiologic studies.296.3w306During sinus rhythm intraatrial conduction periods are normal as is the A-H interval in most patients. The H-V interval is abbreviated because of ventricular preexcitation. During incremental atria1 pacing, the A-H prolongs normally, unlessan enhanced AV node is present, but there is little change in the A-V interval becauseof rapid conduction through the Kent bundle. The His bundle potential gradually moves into the ventricular depolarization complex and may become invisible. If the refractory period of the Kent bundle is longer than that of the normal atrioventricular conduction system,
QRS complex and Narula.‘w
in normals reproduced
and in patients by permission
with various of the author
there will be an abrupt change to normal conduction when the pacing cycle length is shorter than the refractory period of the Kent bundle. Pacing at multiple atria1 sites until the preexcitation is maximized helps to localize the site of the anomalouspathway.304 Atria1 programmed stimulation, early enough to find the Kent bundle refractory to antegrade conduction, still may be conducted rapidly enough through the normal system so that the impulse arrives at the Kent bundle from the ventricular direction before the end of its refractory period. Somewhat earlier premature beats may encounter sufficient delay in the AV node sothat the impulse arrives at the ventricular side of the Kent bundle after the end of its refractory period. Conduction proceeds to the atrium where, if the AV node no longer is refractory, antegrade conduction will occur and the tachycardia is established (Fig. 15). Retrograde conduction in the WPW syn-
58
JOHN
A NSR
C h&mediate
RLateAPC
D. Early APC
APC
Fig. 15. Initiation of tachycardia in patients with WPW syndrome: diagrammatic scenerio. RA, Right atrium: AVN. AV node: RV, right ventricle; LA, left atrium: LV, left ventricle; APC. atrial premature complex. (A) During normal sinus rhythm, conduction proceeds to the AV node and through the Kent bundle, which causes a delta wave. (BI A late APC is blocked in the Kent bundle, but proceeds to the AV node rapidly enough so that the Kent bundle is still in its refractory period. preventing retrograde conduction to the atrium. (Cl A critically timed premature beat is blocked in the Kent bundle and encounters sufficient delay in the AV node so that it is no longer refractory to retrograde conduction and a macroreentrant tachycardia is initiated. (Dl An earlier APC results in block at both the AV node and the Kent bundle.
drome.307-3’0 Ventricular stimulation during sinus rhythm results in ventricular to atria1 conduction with little change in the V-A interval. V-A conduction of an extrastimulus delivered during the refractory period of the His bundle further confirms the presence of an anomalous pathway. This is demonstrated more easily during tachycardia. Electrode positions and endocardial mapping. Strategically placed recording electrodes are able to determine the earliest point of depolarization due to conduction through the Kent bundle. Electrodes are placed in the high right atrium, right ventricle, and His bundle positions. During orthodromic (“SVT”) tachycardia or ventricular stimulation, a mobile lead is maneuvered around the right atrium with particular attention to the tricuspid ring and the time of atria1 depolarization at each point compared with that recorded at the His bundle position. A modification of the Brockenbrough needle, ordinarily used for transeptal catheterization, has proved useful for mapping the tricuspid annu1~s.~‘~Left-sided pathways generally are studied using recording electrodes in the coronary sinus, which runs in the AV groove between the left atrium and ventricle. Observations during tachycardia. The depo-
D. FISHER
larization sequencecan be mapped during tachycardia as described above. Evidence of more than one pathway may be found. During tachycardia with retrograde conduction via the Kent bundle, atria1 stimulation can terminate the tachycardia in several ways: (1) The Kent bundle can be depolarized in an antegrade fashion rendering it refractory when approached by the retrograde impulse. This is most effective when the stimulating electrode is near the Kent bundle. (2) Atria1 stimulation can cause the atrium or the AV node to be refractory to the reentrant wavefront after it passesthrough the Kent bundle. (3) The premature beat may be conducted initially through the atrioventricular conduction system and reach the Kent bundle when it still is refractory to retrograde conduction Similarly, ventricular stimulation can terminate reentrant tachycardia associated with the WPW syndrome by causing refractoriness in the normal atrioventricular conduction system, the ventricle, the Kent bundle, or after retrograde conduction through the Kent bundle by its effects in the atrium. Concurrent .SV7’.3”-313 Patients with the WPW syndrome are not immune to tachycardias due to other mechanisms. AV nodal reentry tachycardias have been identified in such patients and may in fact be the mechanism for tachycardia in some. Automaticity in the anomalous bundle.3’4*3’s Escape beats arising from the anomalous bundle have been documented in patients with WPW syndrome.314Postmortem studies on one patient revealed that the anomalous pathway occurred in a fault in the mitral annulus through which there was a direct AV connection containing P cells resembling those found in the patient’s own sinus node.3’5 Atria1 fibrillation and the WPW syndrome.3’“32’ Atria1 fibrillation conducted rapidly down the Kent bundle can result in extremely rapid ventricular rates, ultimately degenerating into ventricular fibrillation. Digitalis may lengthen or shorten the refractory period of the Kent bundle, slowing or increasing the ventricular rate during atria1 fibrillation. Other drugs, including lidocaine, also have unpredictable effects on Kent bundle conduction. Assessment of the maximum rate of AV conduction across a Kent bundle can be performed in two ways. First, the atrium can be
ELECTROPHYSIOLOGIC
59
TESTING
fibrillated by rapid atria1 pacing or extrastimuli and the shortest R-R interval observed is taken as maximum possible rate. Rapid atria1 pacing provides another, perhaps less accurate, assessment of the maximum possible rate. During atria1 fibrillation, the mean shortest R-R of patients developing ventricular fibrillation was 180 msec, versus 240 in nonfibrillators.320 The weak link hypothesis. In macroreentry tachycardia, such as that associated with WPW syndrome, the impulse travels through a wide variety of tissues, each with its own conduction velocity and refractory period. Susceptibility to block at each of these sites will vary markedly among individuals. In some, the tachycardia can be terminated by block at the AV node using medications such as verapamil, digitalis, and propranolol. In others, the site of the weak link is at the Kent bundle itself, which is most susceptible to the actions of quinidine, procainamide, and disopyramide. Some of the newer antiarrhythmic agents, such as aprindine and amiodarone, also have proved markedly effective in patients with the Wolff-Parkinson-White syndrome. The position of the weak link also dictates the physiologic maneuvers that are most likely to be usefu1.322 In patients with the weak link at the AV node, termination will be enhanced by a supine posture with the legs elevated and by vagal maneuvers such as carotid sinus massage. When termination of the usual form of WPW tachycardia occurs after the ventricular impulse, the accessory pathway is indicated as the weak link. In these patients, termination will be favored by increasing bombardment of the accessory pathway by favoring AV nodal conduction. Therefore, such patients should assume an upright posture with legs dependent, and vagal maneuvers should not be used. Mahaim Fibers: The Pseudo- WP W Syndrome296*306 (Figs. I I, 13, and 14) Mahaim fibers are composed of Purkinje-like fibers that arise prematurely from the AV node (nodoventricular fibers), His bundle, or bundle branches (fasciculoventricular fibers), resulting in a delta wave on the electrocardiogram. Because all impulses traverse the AV node there is some delay and the P-R interval is rarely shorter than 0.12 sec. With incremental atria1
pacing, the A-H interval prolongs and there is no increase in aberrancy such as is seen in the presence of Kent bundles and the WPW syndrome. His bundle pacing normalizes the QRS with nodoventricular fibers (pacing site is distal to the anomalous fibers), but delta waves remain if fasciculoventricular fibers are operative. Discussions of tachycardias related to Mahaim fibers are largely conjectural. The Lown-Ganong-Levine (Figs. 1 I, 12, and 14)
Syndrome296,323-32b
The Lown-Gangong-Levine Syndrome consists of the electrocardiographic pattern of a short P-R interval and a normal QRS complex both during sinus rhythm and (usually) during tachycardia. There are several mechanisms for this pattern. AV nodal bypass tracts (atrio-His tracts).‘23 AV nodal bypass tracts often are referred to as James or Brechenmacher fibers and are conceptualized as strands of the intraatria1 internodal pathways that “miss” the AV node and insert below it in the His bundle. Such pathways are rare.323 With atria1 pacing, the A-H interval remains virtually constant until the refractory period of the pathway is reached. If conduction through the AV node is still possible, the A-H interval jumps to a level appropriate for AV nodal conduction at that rate, mimicking the pattern seen in dual AV nodal pathways except for the flatness of the initial portion of the curve. AV nodal bypass tissues may be affected little by vagal maneuvers. Enhanced AV node conduction.306*324 Enhanced AV node conduction has been defined as an abnormality of AV conduction consisting of (1) A-I-I interval in sinus rhythm 60 msec or less; (2) 1:l AV conduction maintained during atria1 pacing to rates of 200 bpm or more; (3) maximum A-H interval prolongation of 100 msec or less. The AV node remains susceptible to vagal maneuvers and beta blockade. Short P-R interval without enhanced A-V node conduction. In spite of a short A-H and P-R interval during sinus rhythm, the other criteria for enhanced AV node conduction are not met. Typical dual AV node pathways may be identified in some such patients, with the faster pathway having a relatively long refractory period. Normal P-R or A-H longer than 60 msec but
60
other evidence of enhanced AV node conduction or bypass: flat A-H curve, with other criteria of enhanced AV node conclusion (see above); “concealed LGL.” Mechanisms of tachycardia in the LGL syndrome.‘24q325 True AV nodal bypass tracts are rare and probably account for very few instances of tachycardia. AV nodal reentrant tachycardia is the most common mechanism encountered in patients with the LGL syndrome, followed by tachycardias due to concealed Kent bundles, which will be discussed in the next section. Patients with the LGL syndrome may have tachycardia due to other causes, with the short P-R interval acting as an innocent bystander. A high incidence of ventricular arrhythmias, including tachycardia and fibrillation, has been observed in patients with the LGL syndrome.324q326The potential for rapid AV conduction in patients with enhanced AV nodes may increase the risk of ventricular vulnerability in a manner analogous to those with WPW syndrome and rapid conduction of atria1 fibrillation. Tachycardias Related to Concealed Kent Bundles327-333 Some Kent bundles conduct only retrogradely from ventricle to atrium, and therefore are associated with atria1 but not ventricular preexcitation. During sinus rhythm there is nothing on the ECG to reveal the presence of a functioning Kent bundle. Tachycardias due to concealed anomalous (retrograde) conduction account for a large share of supraventricular tachycardias, probably second only to AV nodal reentry. Atria1 fibrillation does not appear to pose an inordinate threat to these patients, as accelerated antegrade conduction down extranodal bypass tracts is not a feature of this condition. Although right-sided bypasses have been described”’ the majority of these tracts appear to be on the left. A “supraventricular tachycardia” with inverted atria1 depolarizations in lead I, in a patient without a history of delta waves during sinus rhythm, usually is due to a left-sided retrograde “concealed Kent bundle.” Electrophysiologic features. During incremental pacing, all intervals behave normally. Incremental ventricular pacing results in retrograde conduction with little or no prolongation of
JOHN
D. FISHER
the V-A interval and a retrograde sequence of depolarization that depends on the location of the bypass tract. Difirential diagnosis. Tachycardias due to concealed retrograde conducting Kent bundles can be differentiated from tachycardias originating in the atrium by observing the sequence of atria1 depolarization during tachycardia or ventricular stimulation. Absence of evidence of dual AV node pathways usually will differentiate these arrhythmias from those due to AV nodal reentry. The possibility of a septal retrograde Kent bundle also must be distinguished from a tachycardia due to James fibers. Variations of the Lown-Ganong-Levine syndrome usually are revealed during sinus rhythm by the short P-R interval and during incremental atria1 pacing by failure of the A-H interval to prolong normally. The differential between a concealed retrograde conducting James fiber and a septal retrograde Kent bundle can be made by taking advantage of the relatively long refractory period of the His-Purkinje system: a ventricular premature beat delivered just after the inscription of the His bundle depolarization would occur at the time when the His bundle is refractory. Therefore, any conduction back to the atrium would have to occur over a pathway that did not include the His-Purkinje system, i.e., over a septal Kent bundle rather than via an atrio-His (James) tract. Bundle branch aberrancy occurs more often in tachycardia involving a Kent bundle than in those related to AV node reentry.33’“32 AV node reentry tachycardias typically are initiated by an atria1 premature beat that conducts antegradely over the slow pathway, giving the His-Purkinje system adequate time for repolarization. In tachycardias involving Kent bundles, antegrade conduction over the AV node is less delayed, and the His-Purkinje system may not be fully repolarized, giving rise to bundle branch aberrancy. Aberrant QRS complex may also be caused by concealed retrograde invasion of the bundle branches.333 Concealed (Retrograde Conducting) Ganong-Levine Equivalent334
Lown-
Ventricular stimulation also can result in atria1 preexcitation in a pattern suggesting partial AV node bypass or enhanced AV node
ELECTROPHYSIOLOGIC
61
TESTING
conduction, or retrograde conducting “James” fibers. The differential diagnosis is outlined above. Concealed (Retrograde Fibers
Conducting)
Mahaim
Retrograde conducting Mahaim fibers, not yet confirmed, but included here for the sake of symmetry, would not be revealed by a delta wave during normal sinus rhythm. Tachycardia might involve a reentrant circuit of Mahaim to ventricle to bundle branches to Mahaim or vice versa. During tachycardia, a bundle branch block pattern would emerge if the Mahaim fibers arose in the bundle branches or if antegrade conduction was via the Mahaim fibers. A normal QRS configuration would persist if the abnormal fibers arose from the His bundle or AV node or whenever antegrade conduction utilized the normal pathways. Diagnostically, evidence of dual AV node pathways or atrioventricular bypass tracts in conjunction with a normal retrograde sequence of atria1 depolarization must be excluded. Premature beats in the atrium would not disturb the timing of this rhythm. Tachycardias associated with Mahaim fibers would include the ventricle in the circuit and ventricular depolarizations would be expected to affect the timing of the tachycardia. Concealed (Retrograde A v Node294.33S.336
Conducting)
Accessory
Accessory pathways with conduction properties typical of AV nodal tissue usually are septal in location. Variants capable only of retrograde conduction predominate. Both paroxysmal and incessant forms of tachycardia occur in patients with accessory AV nodal-like tissues. During ventricular pacing or programmed stimulation, two different atria1 sequences of retrograde activation occur, a phenomenon not yet described with a single AV node.ls2 In some patients,336 the pathway is concealed only because its conduction is slower than that of the normal pathway. A tachycardia equivalent to an antidromic mechanism seen in the WPW syndrome has been observed in one such patient316 Anterograde conduction occurred through the anomalous pathway with a QRS configuration suggestive of right ventricular apical activation and masquerading, therefore, as a ventricular tachycardia.
This tachycardia could be induced by an atria1 premature beat that blocked in the AV node (A-H block) with subsequent conduction down the accessory pathway to the right ventricular apex after a prolonged P-R interval of 300 msec. In contrast to most fibers of the James or Kent type, conduction in accessory AV nodes typically is enhanced by atropine and would be expected to be depressed by vagotonic maneuvers and beta blocking agents. The Role of Electrophysiologic Studies in the Operative Management of Supraventricular and Anomalous Pathway Tachycardias
Indications for Surgery329~337~340 Surgery may be useful in patients with lifethreatening tachycardias unresponsive to medical or pacing therapy. Patients with very rapid paroxysmal tachycardias, utilizing an anomalous antegrade conduction pathway, form the most dramatic group of candidates for surgery. Patients debilitated by the incessant forms of tachycardia may also derive relief from surgery. 329,339 There still is someconcern over the definition of refractoriness to medical and pacer therapy.338In the case of the WPW syndrome, Kent bundles with refractory periods of 270 msecor lesstend to resist pharmacologic modification.340Surgery offers the only definitive cure and might be sought by younger patients who would otherwise have to look forward to a lifetime of medical therapy. Importance of the preoperative study. The advantages of minimizing the number of surprisesand therapeutic decisionsin the operating room are obvious. The effects of anesthesia or inadvertent trauma due to manipulation of the heart during surgery can have important effects on electrophysiology and may prevent the initiation of a tachycardia or temporarily suppress conduction in a bypass tract. In such cases, precise location of the bypass tract during a preoperative study can result in successful “blind” ablation at surgery.34’ Epicardial and endocardial mapping in supraventricular and preexkitation tachycardias263.337m339,34’-345 (Fig. 16). Atria1 endocardial and epicardial mapping have been used to localize intraatrial SVT342 and to identify the AV
62
JOHN
D. FISHER
increased by atria1 pacing at a relatively rapid rate near the site of the bypass, as determined from the preoperative study. Ventricular pacing in patients with WPW syndrome and retrograde conduction over the anomalous pathway results in preexcitation of the atrium at the point of the bypass. In patients whose bypass tract is located in the septum, epicardial breakthrough during atria1 pacing will occur after the onset of the delta wave on the electrocardiogram, and endocardial mapping techniques must be used to complete localization of the bypass. Following attempted surgical correction of the tachycardia, efforts should be made, while in the operating room to confirm the success of the procedure. In patients with WPW syndrome, evidence also should be sought for the existence of additional pathways whose presence may have been masked by more rapid conduction through the previously identified, now ablated, pathway.
HP?4
ANTERIMI
LEFT LATEIL
VENTRICULAR TIfllNG REFERENCE: MA-PI ATRML TIMING REFERENCE: LV-PI ~1
628AC Epicardial mapping the WPW syndrome. The Fig. 16. epicardial surface of the heart is divided into a grid based on that used by Gallagher et al. During pacing of the left atrial appendage, earliest ventricular activation occurs at the base of the left ventricle at the acute margin 110 set after the pacer impulse (PI). Depolarization then proceeds radially. During left ventricular pacing at the point marked by the circled asterisk, the earliest atrial activation is at a point adjacent point. which is activated first during atrial pacing.
node and His bundle for ablation in patients with incessant supraventricular tachycardias.338.339*343 Epicardial mapping has been particularly useful in patients with the WPW syndrome.34’“” The normal sequence of epicardial activation345 begins on the anterior surface of the right ventricle near the left anterior descending artery, remote from the AV ring. In contrast, the earliest epicardia4 activation in patients with Wolff-Parkinson-White syndrome occurs near the AV rings (Fig. 16). Since conduction often occurs via the normal pathway in these patients, the degree of anomalous conduction can be
Surgical Techniques A detailed discussion of surgical techniques is outside the scope of this review. Removal of an atria1 focus may be accomplished through an atriotomy, or amputation in the case of a focus localized to the appendage.342 His bundle ablation has been accomplished by incision, suturing, and injection of sclerosing substances. The large experience at Duke University has led to vast improvements in the surgical approach to WPW.346 Perhaps the most important point is that the Kent bundle may insert anywhere from immediately adjacent to the annulus to a point fairly far out on the ventricular surface (Fig. 17). The usual approach is to make an incision along the mitral annulus centered about the point of the bypass as determined from mapping. Then, working from the inside of the atrium and using blunt and sharp dissection through the incision at the annulus, the epicardial surfaces of the ventricle and often the atrium are denuded over a substantial area. Cryosurgical techniques also have been introduced for treatment of incessant supraventricular tachycardia339.343 and the WPW syndrome.347 Cryosurgery appears to have some advantages. Temporary block of conduction can be achieved by cooling to 0°C. Since recovery of conduction subsequently occurs, any “trial and error”
ELECTROPHYSIOLOGIC
63
TESTING
NERVE HOOK
Fig. 17. Surgical procedure for treatment of WPW. The left-hand panel represents a cross-section of the left side of the heart at the level of the AV groove. Possible Kent bundle locations are shown in black. Successful surgical ablation of the His bundle is accomplished working from inside the atrium through an incision at the ennulus. Epicardial structures are pushed back leaving a denuded left ventricular surface. Based on the experiences at Duke University.
needed to localize the abnormal area need not cause permanent damage to normal tissues. Permanent ablation of the abnormal areas is accomplished with freezing at -60°C for 2 or more 90-set applications. Other benefits of cryosurgery have been observed during acute and chronic animal studies.348When applied to the ventricle, ectopic activity can be localized to the edge of the cryolesion, but this disappearswithin a week, leaving an electrically silent area. Histologically, the chronic cryolesion is a well demarcated firm scar like an innert plug without disruption of surrounding tissues. Electrophysiologic testing for the control of SVT and preexcitation tachycardias will be discussed following the section on ventricular arrhythmias.
Ventricular
Tachycardias
(VT)
Ventricular tachycardias are diverse in origin, configuration, associated disease states, rate, and malignancy.349Many patients referred to the arrhythmia service at our hospital with recurrent ventricular tachycardia had been mistakingly diagnosed as having supraventricular tachycardia with aberrancy. These patients often are
subjected to the usual emergency room routine for the treatment of supraventricular tachycardia, thereby possibly prolonging the duration of the arrhythmia. The responsivenessof some ventricular tachycardias to vagal maneuvers350,35’ only serves to enhance the illusion. Ventricular tachycardia originates in the ventricle, is maintained independently of atria1 participation, and has a rate in excess of that appropriate for an idioventricular rhythm. There does not appear to be any virtue at present to defining VT as a rhythm with a rate in excessof 100 bpm. Although slower rates often are considered to be due to accelerated idioventricular rhythms, some tachycardias with rates well in excess of 100 bpm can be slowed to rates far below 100 bpm under the influence of antiarrhythmic drugs, without change in configurations or, presumaccelerated ably, mechanism. Additionally, idioventricular rhythms may exceed 100 bpm, again without apparent change in configuration or mechanism.
Electrocardiographic Features Classically, the diagnosisof ventricular tachycardia is made easier if conducted sinus beats or
64
JOHN
fusions with sinus beats can be observed during the tachycardia. Unfortunately, in the majority of patients, such conducted beats are not observed because of antegrade refractoriness in the conduction system or because there is sufficient retrograde conduction during ventricular tachycardia to overdrive the atria. Evidence of AV dissociation strongly favors the diagnosis of ventricular tachycardia; rhythms such as AV nodal reentrant tachycardia with retrograde block are much less common. Ventricular tachycardia must be distinguished from supraventricular tachycardia and guidelines have been proposed based on electrophysiologic studies that help make this distinction352 (Fig. 18). Seventy episodes of ventricular tachycardia and 70 episodes of aberrantly conducted supraventricular tachycardia were compared in patients whose baseline cardiograms did not have bundle branch or fascicular block. Findings suggesting a ventricular origin of the tachycardia were: (1) QRS duration greater than 0.14 set; (2) left axis deviation; (3) certain configurational characteristics of the QRS. For patients whose tachycardia had a right bundle branch block configuration during tachycardia, a pure R wave in V 1, an Rsr’, a QR or an RS configuration; in V6 an rS, an S, a QR, possibly a pure R wave. For patients whose tachycardia had a left bundle branch block configuration,
Vl SVT 43 VT 45
22 25
0 12
0 4
V6 SVT 48 VT 45
22 25
0 1
12 10
TOTALS SVT 48 VT 45
22 25
0 13
12 14
*LEFT
BRANCH
BUNDLE
CONFIGURATIONS
7
12 2
17 20
there were no distinguishing characteristics in V 1, but in V6, qR and Qrs complexes were found only in patients with ventricular tachycardia. (4) AV dissociation; (5) rates below 170 bpm for patients with right bundle branch block configuration. A definitive diagnosis is not always possible without invasive studies. Reliable guidelines for patients whose baseline electrocardiogram features partial or complete bundle branch block have not yet been established. During electrophysiologic studies, the diagnosis of ventricular tachycardia may be based on the following observations. (1) The presence of AV dissociation, especially if the block is at the H-V level. (2) Absent or randomly distributed His bundle potentials also are definitive if antidromic tachycardias related to the WPW syndrome have been ruled out. His bundle potentials in regular relationship to the ventricular depolarization can be observed, in somecasesof ventricular tachycardia, by mechanismsthat will be discussedbelow. In such cases,supraventricular tachycardias should be ruled out using criteria described in the sectionson supraventricular tachycardia. (3) The tachycardia should not meet any of the criteria outlined above for supraventricular or preexcitation tachycardias. (4) If a 1:l AV relationship exists, there are three possibilities: isorhythmic tachycardias may coexist; 1:1 V-A conduction may be present; or
28 2
4
10
0
11
9
+
0
12
15
2
0
10
13
31 2
0 6
12
23
2
2
15 14
2 18
31 2
1 18
NOT REPORTED
D. FISHER
SEPARATELY
FOR
l
25
0 1
0 11
22 25
0 1
0 11
---
l
VI
Fig. 18. Differential diagnosis of ventricular tachycardia and aberrantly conducted supraventricular tachycardia. EGG configurations in leads Vl and V6 were compared in 70 episodes each of supraventricular tachycardia with and ventricular tachycardia in patients without bundle block or hemiblock during normal sinus rhythm. Although considerable overlap in sotne patients, other patterns are reasonably specific. (After Wellens.‘“)
Typical aberrancy there is
ELECTROPHYSIOLOGIC
65
TESTING
the rhythm may be supraventricular in origin. Atrial and ventricular pacing and premature beats will establish quickly whether the rhythms are independent or related, as well as the direction of conduction. (5) The effects of atria1 pacing can be most enlightening. The diagnosis of VT is favored if atria1 pacing at or above the tachycardia rate restores in a normal QRS configuration, or if AV block occurs at rates far below that of the tachycardia. If, during VT, atria1 pacing is performed at rates faster than the tachycardia and results in an increase in the ventricular rate without change in the QRS complex, the finding may be nondiagnostic; although compatible with aberrantly conducted supraventricular tachycardia, this also may represent entrainment of a ventricular tachycardia, a phenomenon that will be described briefly in the section on pacing for tachycardias. Mechanisms
of Ventricular
Tachycardia
Ventricular tachycardia may be due to macroor microreentry, automaticity, and triggered automaticity. As discussed previously, the clinical differential is difficult to make with great confidence. Sequential changes following experimental myocardial &hernia or infarction.353”62. Immediately following experimental coronary occlusion there are abrupt changes favoring the development of reentry arrhythmias; commonly a relatively slow idioventricular rate punctuated by episodes of ventricular tachycardia and fibrillation persists for approximately 20 min following occlusion. The dispersion of refractoriness and conduction properties is enhanced by rapid rates whether due to pacing, sympathetic tone, or atropine, and these are accompanied by exacerbation of the arrhythmia. Vagal tone, or withdrawal of sympathetic tone, tends to decrease the electrophysiologic disparities and the incidence of arrhythmia. Reperfusion of an occluded area before irreversible damage has occurred results in a different type of malignant arrhythmia.357~358 The idioventricular rate between episodes of tachycardia or fibrillation is faster than during occlusion. The arrhythmias are unaffected by changes in autonomic tone, but may be suppressed by rapid pacing. These findings are consistent with an automatic mechanism, but
inhomogeneous improvement in conduction also may establish reentrant pathways. Twenty-four hours following this experimental coronary occlusion, initial electrical activity, during arrhythmias, appears to arise within the surviving subendocardial Purkinje cells.359m360 The arrhythmias have the characteristics of enhanced automaticity. Three to 9 days after experimental myocardial infarction, evidence of enhanced automaticity usually declines. Recordings from multiple sites in the infarcted area, using a composite electrode, documents the presence of continuous electrical activity with low amplitude potentials bridging the diastolic interval between beats, resulting in a reentrant type of arrhythmia.36’ In the chronic postinfarction period, from months to years following the initial event, subendocardial tissues, especially Purkinje fibers, remain histologically intact in spite of extensive scar formation in the area of the infarct.3s3’362 Reentry in the His-Purkinje system. Reentrant circuits involving the Purkinje system have been demonstrated in experimental preparations.7’“63 Reentry in the human His-Purkinje system has been documented364 during right ventricular apical programmed stimulation. A critically timed beat finds the right bundle branch refractory to retrograde conduction. Slow conduction to the left ventricle finds the left bundle receptive to retrograde conduction. The impulse travels retrogradely up the left bundle and His bundle and produces a reentrant ventricular systole by antegrade conduction down the right bundle branch. A recently described variant produces intraventricular reentry with a narrow QRS complex.365 The retrograde limb was one of the divisions of the left bundle branch and the antegrade limb was (simultaneous conduction) in the right bundle branch and the other division of the left bundle branch. Reentry tachycardias with the main bundle branches participating in the circuit (macroreentry) have been reported3’j6 but are felt presently to be uncommon. Microreentry. Most cases of ventricular tachycardia appear to be due to a microreentrant circuit localized within a limited area of the ventricle. Evidence for such microreentry circUits367,368 Include . the following: (1) lack of
66
JOHN
retrograde His-Purkinje conduction delay for initiation of tachycardia; (2) bundle branch reentry not required for initiation of tachycardia; (3) the presence of H-V block has no effect on the tachycardia; (4) random retrograde His bundle potentials observed during tachycardia; (5) large segments of both ventricles can be captured without affecting the tachycardia; (6) conducted supraventricular beats fail to affect the timing of the tachycardia; (7) areas of continuous local electrical activity, analogous to that observed in experimental infarctions, have been observed in patients with aneurysms.369 Tachycardias with different QRS configurations in the same patient may indicate the existence of more than one ectopic (microreentrant) circuit, or multiple points of exit or change in conduction within a single area.“‘.“’ Automaticity. The potential for automatic tachycardias was outlined above in the section on the course of arrhythmias following experimental myocardial infarction. The possibility of triggered automaticity in one patient has been raised.“’ In patients with known recurrent sustained tachycardia, the arrhythmia can be reproduced by programmed stimulation in most cases, suggesting further that reentry is the chief mechanism for ventricular tachycardia in man. Programmed stimulation would not be expected to initiate or terminate tachycardia due to enhanced automaticity. Arrhythmias due to triggered automaticity should be sensitive to verapamil, an agent, however, which clinically has been of indifferent effectiveness in ventricular tachycardia. Ventricular
Fibrillation
This most disastrous of ventricular arrhythmias may be defined as chaotic, random, asynchronous activity of the ventricles due to repetitive reentrant excitation and/or focal discharge.“’ Ventricular fibrillation is facilitated by inhomogeneity in conduction velocity and refractory periods and by a large ventricular mass. Ventricular fibrillation is difficult to achieve experimentally in small hearts or in small portions of large hearts, the critical mass in ventricular muscle requiring a surface area of at least 4 sq cm.“’ Microelectrode studies have not revealed characteristic abnormalities in the cells of a fibrillating preparation, but the rapid
D. FISHER
rate results in slowly rising action potentials and asynchronous depolarization of closely adjacent cells, tending to perpetuate the arrhythmia.373 When ventricular fibrillation occurs during eiectrophysiologic studies in humans, it usually is caused by two ventricular programmed extrastimuli in patients with documented or suspected ventricular tachycardia or fibrillation.374 Ventricular fibrillation occurring during electrophysiologic studies begins, in most patients, as a rapid and accelerating ventricular tachycardia with discrete local electrograms that ultimately become fragmented and disorganized. Experimentally, the ventricular fibrillation threshold (VFT) is measured by applying stimulation at increasing amplitudes until fibrillation occurs.375 The VFT in humans undergoing open heart surgery376”77 were less than 20 mA in patients with coronary disease and more than 20 mA in patients undergoing surgery for correction of congenital defects or valvular heart disease. Electrophysiologic Studies in Patients With Ventricular Tachycardia349~37s”91 Electrophysiologic studies are useful in establishing the most effective medical or pacing treatment for recurrent tachycardia or in laying the groundwork for surgery. As with other tachycardias, much can be learned by observations during (1) induction of tachycardia; (2) established tachycardia; (3) termination of tachycardia. Stimulation techniques. Programmed stimulation, burst, and ramp pacing have been described earlier and all are useful in the study of ventricular tachycardia. Atria1 stimulation. Atria1 programmed extrastimuli or incremental pacing may result in the induction of ventricular tachycardia.392 Ventricular stimulation. Incremental ventricular pacing occasionally results in the induction of tachycardia, but as a rule, does not offer important insight into the mechanism of VT. Programmed extrastimuli (PES), however, commonly result in the induction of ventricular tachycardia in patients with a history of such an arrhythmia. (details are provided below in the section on serial testing). In some patients, two tachycardia induction zones can be determined.“’ In patients with a wide tachycardia initiation zone, there may be an inverse relation-
ELECTROPHYSIOLOGIC
TESTING
during the refractory period and the duration calculated to result in a single capture. If the termination zone immediately follows the end of the refractory period, a train of 10 stimuli will ensure early capture and termination. Multiple captures for tachycardia termination. 393-395In some patients, interruption of the reentrant circuit or overdrive suppression may require several consecutive captures at periods above the tachycardia. Bursts of rapid pacing are usually more effective than underdrive, overdrive, or the tune-down method described below. Overdrive pacing for tachycardia termination.379,393-395,42”425 Classical overdrive pacing rates are slightly in excess of the tachycardia for several seconds to several minutes. Although there are no fixed upper limits, prolonged pacing at rates significantly above the tachycardia rate generally is not well tolerated. In some tachycardias, with Entrainment.28’ pacing rates slightly in excess of the tachycardia, entrainment results in an ECG complex that resembles either the tachycardia or some degree of fusion rather than a typical paced configuration. As the pacing rate is increased to a critical rate, entrainment ceases, and the ECG complex undergoes an abrupt change to a purely paced configuration. In some cases, cessation of pacing at this point is followed by termination of the tachycardia. The entrainment technique has proved particularly useful in the treatment of atrial flutter. Some cases of ventricular tachycardia also follow this sequence. Permanent pacers are rarely used for entrainment (Fig. 24). Tune-down or decremental ramp technique. 394,39s,440Sudden cessation of overdrive pacing may result in the reinitiation of tachycardia. Some of these patients can be successfully managed by slowing the pacing rate gradually to more physiologic rates before the pacemaker is turned off. Burst pacing (Fig. 24).393 An arbitrary but clinically useful distinction can be made between overdrive and burst pacing, which may be defined as approximately 4-l 5 stimuli at rates of 30 bpm or more faster than the tachycardia. A study of 573 episodes of ventricular tachycardia suggested that bursts of rapid ventricular pacing were more effective than programmed extrastimuli or overdrive. Acceleration of the tachycardia can occur, however, as with other methods of
Fig. 24. Rapid ventricular pacing for termination of ventricular tachycardia (VT). (Al VT at 125 bpm with a right bundle, right axis deviation configuration. Ventricular pacing was initiated at a rate just below that of the tachycardia. The pacing rate was gradually increased to 194 bpm, with capture at 143 bpm. but the tachycardia was not terminated. At 143 bpm. the QRS configuration was right bundle, left axis, i.e., a fusion between the VT configuration and the left bundle, left axis seen with “pure” pacing from this right ventricular apical site. When such fusion or “entrainment” occurs, it is almost necessary to pace at faster rates to get beyond the zone of entrainment and achieve a purely paced configuration. In this case. 194 bpm did not prove sufficient to terminate the VT. Prolonged pacing at such rates is not well tolerated by most patients, so burst pacing was subsequently used. (6) A burst of rapid ventricular (ERVPI for 5-6 captures at 194 bpm is ineffective, but BRVP at 205 bpm for 5 captures terminates the VT. Decremental, or incremental followed by decremental ramp pacing may also prove effective in some cases (see text.)
pacing, and care must be taken to establish the safety zones of both the rate and duration of the burst.
Indications Temporary pacing. Temporary pacing for control of tachycardias is indicated when the arrhythmia recurs in spite of intensive pharmacologic therapy. There are no specific contraindications to temporary pacing, even burst pacing, for control of tachycardia, but the physician must ensure that alternative methods of termination are available, including trained personnel and equipment for direct current cardioversion. Implantable antitachycardia pacemakers. 395*4’3.420A47The Intersociety Commission on Heart Disease has modified its widely used three-letter pace code to a five-letter code, partly
68
Programmed or random extrasystoles, underdrive pacing, overdrive pacing, bursts, decremental ramps (tune down), and incremental ramps or entrainment and trains of very rapid stimuli have all been used successfully in the termination of ventricular tachycardia.393”95 Bursts of rapid ventricular pacing are probably the most effective and reliable method for termination of tachycardia. Success with burst pacing does not depend on whether the tachycardia is due to automaticity or to reentry, termination being due to overdrive suppression in the former and interruption of the circuit in the latter. Pacing for tachycardia termination will be covered in greater detail later. Endocardial mapping.266 Catheters positioned in the right ventricular inflow (the His bundle position), the right ventricular apex, the right ventricular outflow, and the coronary sinus for the posterobasilar left ventricle, together with information from the peripheral ECG, often permit a general localization of the initial point of myocardial activation during centricular tachycardia. Also sought, during NSR, is evidence of abnormal isolated (delayed, fractionated) local potentials. More detailed information can be obtained using mobile catheters in the right and left ventricle. Accuracy is further enhanced if mapping is performed during surgery rather than with catheters. pacemapping makes similar use of mobile electrodes to stimulate the ventricle in each area of the grid during a baseline sinus rhythm until the paced QRS configuration precisely mimicks that of the ventricular tachycardia.367 Mapping studies have revealed that the presence of a right or left bundle branch block pattern during tachycardia is not a safe guide to predicting the chamber of origin, especially in patients with myocardial infarctions involving the interventricular septum. Endocardial mapping also may reveal the presence of diastolic depolarizations or a continuous electrical activity that also may be used to localize the tachycardia: presumably the catheters are recording impulses that are part of the reentrant circuit, some portion of which must remain in a state of depolarization at all times during the cardiac cycle. The role and relative importance of information gained by endocardial mapping in patients not proposed for antitachycardia surgery remains undefined.
JOHN
D. FISHER
The Role of Electrophysiologic Studies in the Operative Management of Ventricular Tachycardias394-4’0 Indications for surgery. Cardiac surgery is indicated in patients whose recurrent ventricular tachycardias are resistant or refractory to medical and pacemaker therapy. Philosophical differences exist as to the definition of “resistant” or “refractory” so that the percentage of patients with recurrent ventricular tachycardia who are referred for surgery will vary widely among institutions. In addition, patients may be referred earlier if there are other indications for surgery such as angina or congenital heart disease. Intraoperative studies. Insofar as possible, mapping studies are performed with the patient normothermic and not on bypass. Epicardial mapping during sinus rhythm may reveal areas of late depolarization that will merit particular attention during tachycardia as a possible site of origin of the arrhythmia. Pacemapping may be performed at the same time as mapping during sinus rhythm; comparison of the resulting QRS complexes with those occurring during the patient’s tachycardia are helpful in localizing the site of the arrhythmia. Epicardial mapping during tachycardia again is performed with the patient at or very near to normothermia, but heart/lung bypass is usually required. The earliest site of epicardial breakthrough is noted and compared with the site estimated during pacemapping. Endocardial mapping is performed, usually through the incised aneurysm or old myocardial scar.396 Surgical techniques. (1) Aneurysmectomy with endocardial excision or stripping in the area of the tachycardia focus as determined by endocardial mapping.3969397This technique recognizes that the extent of scarring is greater on the endocardial than epicardial surface and that the majority of tachycardias probably arise in the border zone near the endocardial surface. (2) Division of the bundle branches in patients thought to have macroreentry tachycardia involving the major branches of His-Purkinje system.366 (3) Ventriculotomy at the site of the tachycardia as determined by mapping.399*400(4) Cryoblation of the tachycardia focus as determined by mapping.402 (5) Aneurysmectomy (without stripping) following mapping localization of the focus to the aneurysm.m’ (6) Aneu-
ELECTROPHYSIOLOGIC
69
TESTING
rysmectomy without mapping.403407 (7) Aneurysmectomy without mapping but with addition of encircling endocardial ventriculotomy.398 This incision surrounds the border zone and extends from endocardium through to the epicardium, in the hopes of electrically isolating any impulses arising from a tachycardia focus. (8) Coronary artery bypass grafting is done as needed with each of the above operations. In patients with a surgically resectable aneurysm or scar, surgical results are not as good if the operation is limited to coronary artery bypass alone.403V404 (9) Cervical sympathectomy or stellate ganglion block, particularly useful in patients with a long QT snydrome, not requiring open heart sur408410 gery. Surgical therResults of surgical therapy. apy appears to be useful in the control of recurrent ventricular tachycardia. Series in which mapping techniques were employed have a higher success rate, especially in achieving total remission of ventricular tachycardia. If preoperative electrophysiologic studies confirm that the tachycardia focus is in an aneurysm, intraoperative studies may not be required if encircling endocardial ventriculotomy can be
performed. In patients with massive aneurysms, the encircling ventriculotomy may encompass excessive amounts of remaining viable muscle, and in such cases, the endocardial stripping approach would be preferable. Serial Electrophysiologic Testing for the Control of Recurrent Tachycardias 349,379.382-385.390.392.394.41
I-417
Concept I. In the absence of previous tachycardia or syncope, tachycardia is rarely produced by electrophysiologic stresses including l-3 programmed estrastimuli or rapid pacing83 349,379-38’*384 (Fig. 19 and 20.) In patients with recurrent Concept II. tachycardias, it usually is possible to duplicate the rate and configuration of the spontaneous tachycardia under controlled catheterization laboratory conditions using the stresses listed (Tables 7 and under concept I 8.349.379-390,384.411417 8). Concept III. Once induced, tachycardias usually can be terminated by pacer techniques, permitting serial testing of antiarrhythmic drugs without direct current cardioversion, thus increasing patient acceptance.3491 379,393m395
Ventricular tachycardia is not induced by triple ventricular premature Fig. 19. patient with a history of syncope and right bundle branch block together with ventricular arrhythmias on several Halter monitors. Leads I. II. AVF. and Vl are electrogram and recordings from the high right atrium.
beats during ventricular left axis deviation, but displayed together with
pacing in this no evidence of the HIS bundle
JOHN
Fig. 20. capture fails
Ventricular to induce
ramp tachycardia
pacing in which in the same
the rate is rapidly patient illustrated
accelerated in Fig. 18.
Serial Electrophysiologic-Pharmacologic Testing: Protocol (Fig. 20)
See recent review in this journal. Candidates for Serial Testing Most investigators in this field agree that patients with recurrent, life-threatening tachycardias should undergo serial testing in an experienced center. Patients with recurrent nonlethal tachycardias, which have nevertheless proved 7.
Atrial
Vulnerability
to Electrophysiologic SVT
Patient
Group
bpm
or the
maximum
permitting
I:1
refractory to multiple drug trials, also are considered. Whether patients who have suffered a single episode of ventricular tachycardia not related to myocardial infarction should undergo invasive studies as yet is unsettled. Survivors of cardiac arrest will probably increasingly become sugjects for serial testing.4’4~4’5~418 Patients with acute anterior wall mycoardial infarctions and any complete bundle branch block may have as much as a 36% incidence of unheralded ventricular tachycardia or fibrillation in the 6 wk following myocardial infarction419 Survivors of myocardial infarction with more than one ventricular premature beat in response to a single programmed extrastimulus may be at dire risk of subsequent VT or sudden death.39’ These
Concept IV. The efficacy of antiarrhythmic therapy can be judged by the degree to which the normal response (concept I) to stresses is restored.349.379.382-38s. 392,41 I-417
Table
to 250
D. FISHER
Initiated/No.
Total
Stressasc”8
Patients
Tested/Percent
1 PES
2-3
SRAP
PES
Controls
6/52/12
l/52/2
4/31/13
l/3/33
suo
7129124
l/29/3
6/20/30
Of2/o
All sss
9131129
o/3
9/16/56
l/2/50
SB
4/25/16
o/25/0
4/l
1 I2150
BTS
5/6/83
O/6/0
5/6/83
o/o/o
28/40/70
10/39/26
1 S/26/69
4/6/67
SVT SVf
group,
SVT.
patients
with
supraventricular
extrastimuli;
BRAP,
brady-tachy
syndrome.
documented
tachycardia burst
of rapid
spontaneous of all types,
atrial
pacing:
1 JO
o/40
SVT. lasting
SUO,
a minimum
syncope
of several
of unknown
origin;
seconds, SSS,
and sick
sinus
excluding syndrome;
echo
beats; SE,
sinus
PES,
programmed
bradycardia;
BTS,
ELECTROPHYSIOLOGIC
TESTING
71
Table
8.
Ventricular
Vulnerability
Total
Fisher et aL3s0 (updated 8 1 Patients
BRVP/RAMPS
%
VT
Att
%
VT
Att
%
VT
Att
%
VT
79
82
96.3
14
81
17.3
27
69
39.1
36
45
80.0
11
4
15
26.7
0
15
0.0
1
14
7.1
3
11
27.3
14
51
27.5
2
51
3.9
3
48
6.3
10
42
5
105
0
105
0.0
1
53
1.9
4
40.3
16
252
6.3
Att
Other %
VT Att
%
to 3/80) 18
61.1
4
4
100.0
1
8
12.5
0
2
23.8
0
25
0.0
1
3
35
11.4
0
15
0.0
0
3
18.2
5
12
0.0
4.8
33.3 0.0
pts) 102
(57 pts) Nonsustained
253
32
184
17.4
53
133
39.8
12
66
41.7
23
-
-
-
-
-
12
5422
--
-
13
-
-
-
-
-
5
2917
--
-
126
2.3-
-
-
0 443
studies)
VT
(29 pts) Control
54
57
95
19
18
29
62
4
3
443
0.7
57
35
2914
0 443
0
3
0
-
-
-
pts)
Att = Patients with VT induction PES = Programmed extrastimuli. VT = Vantrtcular tachycardia. 8RVP Other
3 PES
pt.4
(252 pts, 254 Vandepol et aL3” Sustained VT
(443
2 PES
Att
(51 pts) Control (105 Total
1 PES
Stresses
VT
(83 studies) Former VT (15 suo
to Electrophysioligc
= Bursts = Addition
pt = Patients. SUO = Syncope
attempted.
of rapid ventricular of isooroterenol, of unknown
pacing. with or without
PES; inhibition
pacer,
etc.
origin.
patients are potential candidates for serial electrophysiologic-pharmacologic testing. Some investigators have reported that it is difficult to induce a tachycardia in the Catheterization Laboratory in patients with exerciserelated tachycardias.378 We have not found this to be the case. Electrophysiologic
of permanent
Testing (Fig. 21)
Whenever possible, antiarrhythmic drugs are discontinued for a substantial period of time prior to the test. From 24 to 48 hrs, or five drug half-lifes have been used as guides to timing the discontinuation of drugs prior to testing. In patients with incessant tachycardias, it may be wise to initiate testing while the patient is on a regimen that results in acceptable toleration of the tachycardia. Step 1. Attempts are made to induce the tachycardia using programmed extrastimuli, rapid atria1 or ventricular pacing, and other techniques. Step II. Once tachycardia has been induced, the patient’s hemodynamic status is evaluated immediately. If the tachycardia is well tol-
erated, rate, configuration, depolarization sequence, and diagnosis or type are analyzed. If the ventricular rate is rapid or the hemodynamits are not stable, the tachycardia is terminated as rapidly as possibleusing pacer techniques or DC cardioversion. Step III. Oral or intravenous medications are given, the choice depending on the type of tachycardia, the patient’s history, agents of particular interest to the investigator, and the appropriateness of an agent for the tachycardia being studied. If tachycardia is reinitiated, another drug may be added to the first and the sequencerepeated. Step IV. Subsequent days. A temporary pacemaker electrode is left in place from the first day of study in the position most effective in initiating and terminating the tachycardia. If a promising agent was found during the initial studies, the patient is retested for confirmation on an oral regimen. Drug blood levels should be obtained during initial studies and during serial testing to ensurethat a given drug has received a fair trial and to establish guidelines for future therapy.
72
JOHN
D. FISHER
SERIALELECTROPHYSIOLOGIC-PHARK4COLOGIC TESTING ATTEMPT TACHYCARDIA INDUCTION WITHELECTROPHYSIOLOGIC STRESSES NOTACHYCARDIA-TACHYCARDIA = NOVULNERABILITY =VULNERABLE PACERTERMINATION r NOTPOSSIBLEIPOSSIBLE iiiTzz?= ADMINISTERDRUGSINTRAVENOUSLY AGAINATTEMPT TICHYCARDIAINDUCTION NOTPOSSIBLE t
POSSIBLE
BEGIN ORALEQUIVALENT t RE-TESTUSINGTEMPORARY WIRE LEFT IN PLACEAFTER INITIAL DAY’S TESTING
TERMINATE
NORELIABLEPACER-I TERMINATION t SURGERY,PSYCH ETC,
End points in serial testing. Ideally, a regimen eventually is identified on which it is impossible to reinitiate the patient’s tachycardia. Partial protection implies that the tachycardia zone has become narrower, the rate slower, the hemodynamics improved, or reliable termination by an implanted pacer is possible. The only way available at present to assess whether pacing is efficacious, is to record several 24-hr Holter monitors during spontaneous and during paced rhythm, observing the relative incidence of pauses and premature beats. Indeed, serial Holter monitors during the course of serial electrophysiologic testing may add an important dimension to the assessment of therapy. Alternatives: Pacing and surgery. Pacing for termination rather than prevention represents the pound of cure rather than the ounce of prevention, but seems certain to play an increasing role in the future therapy of arrhythmias. The value of cardiac surgery is also increasing. results
OfSerial
Testing349.379,38~38’,392,411~17
Serial electrophysiologic-pharmacologic testing for the control of recurrent tachycardias has
-qADDOTHERDRUG(S) NOFULLYPROTECTIVE DRUGSIDENTIFIED RELIkLE PACER
IMPliVrTED ANTITACHYCARDIA PACER
Fig. 21. Serial tasting scenerio. Flow diagram of sequanta used during serial alactrophysiologic pharmacologic testing for control of recurrent tachycardias. The actual point at which surgical or implanted pacemaker therapy would be chosen will depend on the characteristics of the patient undergoing study, and the axpartisa of the institution or referral center.
been reported from several centers. The procedure has proved remarkably safe, considering the arrhythmias induced and the incidence of major complications including death, cerebrovascular accident, and myocardial infarctions has been exceedingly small. Reduction of the number and duration of hospital admissions after serial testing brings savings in hospital costs and work days lost. The psychologic benefits to the patient who is relieved of a “sword of Damocles” are manifest. Pacing in the Treatment Tachycardia
of Recurrent
Progress in electrophysiologic testing techniques has contributed to major advances in the pacer treatment of tachycardias. Several pacing techniques have proven useful for temporary and long-term pacing. Tachycardia Prevention379’394’395 Rate support.420V42’ In the presence of profound bradycardia, atria1 and ventricular tachycardias may develop as escape rhythms. Such patients would ordinarily receive pacemak-
ELECTROPHYSIOLOGIC
73
TESTING
present during regular supraventricular tachycardia. While implanted units have been adapted for permanent rapid atria1 pacing,426 the technique most often is on a temporary basis following open heart surgery.427 Paired and coupled pacing.428-430 In paired pacing, an initial stimulus (Sl) is followed by a second stimulus (S2), with the SlS2 interval being shorter than the S2Sl interval. In coupled pacing, the patient’s natural depolarization acts as the Sl and a pacer stimulus as S2. When used in the ventricle, the S2 is timed to produce an electrical, but not a mechanical response.
ers for treatment of bradycardia, and prevention of tachycardia is a secondary benefit. Overdrive suppression.422425 Pacing at rates slightly in excess of a normal rhythm may help to reduce the number of premature beats if they are associated with the initiation of tachycardia. Occasionally, rates of 90-l 10 bpm are required, acutely and chronically, for suppression of tachycardia, and rarely, rates as high as 150 bpm may be needed. During electrophysiologic studies it is common that tachycardia initiation is more difficult during sinus or atria1 rhythms than during ventricular pacing. Implanted atria1 pacemakers may, therefore, be advantageous when used for prevention of ventricular tachycardia. Rate Control Without Termination425430
Pacing for Tachycardia Termination379*395 Single Capture Tachycardia Termination Slow competitive or “underdrive” pacing is useful primarily in patients whose tachycardias have a wise termination zone for a single stimu1~s~~~ (Fig. 22). Conventional AA1 and VVI demand pacemakers can be used, activated by placing a magnet over the unit. Dual demand pacemakers (single chamber slow competitive type)43’ operate as standard demand pacemakers in a bradycardia prevention
Tachycardia
Continuous rapid pacing.425427 In patients with incessant supraventricular tachycardias, reduction in ventricular rate can be achieved by rapid atria1 pacing at a rate that results in 2:1 AV conduction. Induced atria1 fibrillation may result in a slower ventricular rate than was
I
'1
Fig. 22. Termination of ventricular tachycardia by underdrive pacing or single programmed extrastimuli. Peripheral leads I, II, AVF, and Vl are displayed together with the His bundle electrogram and recordings from the low lateral right atrium and the right ventricular outflow, where premature beats are given at the points designated by the arrows. Eventually, the techycardia is terminated. The right ventricular pacing was in the form of programmed extrastimuli, but underdrive pacing would have a similar appearance.
74
JOHN
Table
9.
Dual
Chamber
Pacing
(Tachycardiaj-’ Pacing
Special VAT, OP*
Pacer
HR (bpml
(Devices)
DDD,
<150(V) 2150 (VI < 124 (A,V)
ON (Medtronic)
124-185(A) > 185 (A) l P: Nonstandard HR. heart
rate;
code bpm,
for prevention beats
per minute;
(in these
by rendering
Rate AV Interval
(bpm)
All All
DDT, OP’ (Medtronic) DVI, MN (Medtronic)
reentry
D. FISHER
circuit
lsorhythmic
30 msec
lsorhythmic DVI 77
Simultaneous Programmable 65 msec
(Isorhythmic) V: l/2 A rate
180 180
msec msec
73
180
msec
refractory).
code
is after
ICHD
(Fig. 26).
AV. atrioventricular.
role. With the onset of tachycardia, they are activated automatically, emit stimuli at the same rate as their conventional demand rate, and continue to pace until they sense the termination of the tachycardia. Upside-down demand pacemakers have no conventional demand role, but do respond with slow competitive pacing in the event of a tachycardia.432 Dual chamber pacers. Some AV nodal reentrant tachycardias or tachycardias related to the Wolff-Parkinson-White syndrome can be terminated most reliably by simultaneous or nearly simultaneous atria1 and ventricular stimulation, which can be accomplished by modified AV sequential (DVI) or atria1 synchronous pacemakers (VAT,DDT)433A36 (Table 9). Autoscan pacemakers.437 To minimize the delay in termination associated with fixed rate underdrive pacing, these proceed, in a variety of
Fig. 23. Termination of ventricular tachycardia displayed together with a right ventricular recording. train of 10 stimuli with a cycle length of 7.5 msec.
by a train Ventricular
orderly programs, to scan the diastolic period of the tachycardia with premature beats. Orthorhythmic pacing.438 The orthorhythmic pacemaker (Savita) is a multicapable tabletop unit designed for automatic termination or prevention of tachycardia. The unit can be programmed to perform underdrive pacing either at a fixed rate or at a percentage of the tachycardia cycle length. The orthorhythmic pacemaker has enjoyed some success in an “abort” mode, programmed to insert one or more stimuli immediately after spontaneous extrasystoles to abort the development of a sustained tachycardia. Trains.‘94,439 A short train (Fig. 23) of extremely rapid stimuli with cycle lengths of 2-40 msec provides another approach to the problem of a very narrow tachycardia termination zone. The onset of the train is timed to begin
of ultrarapid tachycardia
stimulation. at a cycle
ECG leads, I. II. AVF. and length of 410 msec is terminated
Vl
are by a
ELECTROPHYSIOLOGIC
TESTING
during the refractory period and the duration calculated to result in a single capture. If the termination zone immediately follows the end of the refractory period, a train of 10 stimuli will ensure early capture and termination. Multiple captures for tachycardia termination. 393-395In some patients, interruption of the reentrant circuit or overdrive suppression may require several consecutive captures at periods above the tachycardia. Bursts of rapid pacing are usually more effective than underdrive, overdrive, or the tune-down method described below. Overdrive pacing for tachycardia termination.379,393-395,42”425 Classical overdrive pacing rates are slightly in excess of the tachycardia for several seconds to several minutes. Although there are no fixed upper limits, prolonged pacing at rates significantly above the tachycardia rate generally is not well tolerated. In some tachycardias, with Entrainment.28’ pacing rates slightly in excess of the tachycardia, entrainment results in an ECG complex that resembles either the tachycardia or some degree of fusion rather than a typical paced configuration. As the pacing rate is increased to a critical rate, entrainment ceases, and the ECG complex undergoes an abrupt change to a purely paced configuration. In some cases, cessation of pacing at this point is followed by termination of the tachycardia. The entrainment technique has proved particularly useful in the treatment of atrial flutter. Some cases of ventricular tachycardia also follow this sequence. Permanent pacers are rarely used for entrainment (Fig. 24). Tune-down or decremental ramp technique. 394,39s,440Sudden cessation of overdrive pacing may result in the reinitiation of tachycardia. Some of these patients can be successfully managed by slowing the pacing rate gradually to more physiologic rates before the pacemaker is turned off. Burst pacing (Fig. 24).393 An arbitrary but clinically useful distinction can be made between overdrive and burst pacing, which may be defined as approximately 4-l 5 stimuli at rates of 30 bpm or more faster than the tachycardia. A study of 573 episodes of ventricular tachycardia suggested that bursts of rapid ventricular pacing were more effective than programmed extrastimuli or overdrive. Acceleration of the tachycardia can occur, however, as with other methods of
Fig. 24. Rapid ventricular pacing for termination of ventricular tachycardia (VT). (Al VT at 125 bpm with a right bundle, right axis deviation configuration. Ventricular pacing was initiated at a rate just below that of the tachycardia. The pacing rate was gradually increased to 194 bpm, with capture at 143 bpm. but the tachycardia was not terminated. At 143 bpm. the QRS configuration was right bundle, left axis, i.e., a fusion between the VT configuration and the left bundle, left axis seen with “pure” pacing from this right ventricular apical site. When such fusion or “entrainment” occurs, it is almost necessary to pace at faster rates to get beyond the zone of entrainment and achieve a purely paced configuration. In this case. 194 bpm did not prove sufficient to terminate the VT. Prolonged pacing at such rates is not well tolerated by most patients, so burst pacing was subsequently used. (6) A burst of rapid ventricular (ERVPI for 5-6 captures at 194 bpm is ineffective, but BRVP at 205 bpm for 5 captures terminates the VT. Decremental, or incremental followed by decremental ramp pacing may also prove effective in some cases (see text.)
pacing, and care must be taken to establish the safety zones of both the rate and duration of the burst.
Indications Temporary pacing. Temporary pacing for control of tachycardias is indicated when the arrhythmia recurs in spite of intensive pharmacologic therapy. There are no specific contraindications to temporary pacing, even burst pacing, for control of tachycardia, but the physician must ensure that alternative methods of termination are available, including trained personnel and equipment for direct current cardioversion. Implantable antitachycardia pacemakers. 395*4’3.420A47The Intersociety Commission on Heart Disease has modified its widely used three-letter pace code to a five-letter code, partly
76
JOHN
to cope with the profusion of antitachycardia pacers446 (Fig. 25). The indications for implantable pacemakers for the control of tachycardias are more strict in order to avoid the acceleration of a ventricular tachycardia, which may prove catastrophic. For reasonable security, scores of episodes should be terminated reliably preimplantation, using a temporary pacemaker with implantation parameters, under a variety of conditions, i.e., peak and trough blood drug levels, different body positions, and varying times of the day and night. The safest approach for patients who tolerate the arrhythmia well may be implantation of a manually activated unit that can be used after the patient arrives in the emergency room, with electrocardiographic confirmation of the tachycardia and with direct current cardioversion available. Automatic pacemakers may be appropriate in patients who rapidly develop syncope or hemodynamic decompensation with their tachycardias, or who have very frequent episodes of the arrhythmia. Other candidates include patients who are unaware of the presence of tachycardia prior to hemodynamic decompensation. Some patients are unable to cope psychologically with the responsibilities of a manual system, and such patients may benefit from an automatic pacemaker.
Automatic
implanted
trode mesh capping the apex of the heart, implanted through a left thoracotomy. Unlike regular tachycardias, many forms of ventricular fibri11ation37’*447 are characterized by chaotic wave forms without isoelectric potential segments. In addition to a conventional sensing circuit, the implantable defibrillator senses the absence of isoelectric periods and after approximately 15 set, emits a truncated exponential pulse of up to 30 joules. After extensive development and animal trials, implantations have begun in humans with refractory recurrent ventricular fibrillation and rapid ventricular tachycardia. Syncope of Unknown
defibrillators.447
1
2
3
4
5
CATEGORY
Chambsr(s) Paced
Chamber(s) sensed
Mode of Responss(s)
Programmable FUnctions
Speciil ahythmia
Letters Used
V-venwck
V-vantrlck
T-Triggared
P- Programin&Is (Flate&lbr Outpra
B-Bursts
A-Atrium
A-Atrium
I-lnhibitii
M-multiprogrammable
N-Normal Competition
D-Double
D-mle
D-Double*
o-Nma
S-Scanning
O-None
o-Ncms
E-External
R-REVSlfW
L * Atrial
triggered
and
ventricular
inhibited
Origin (SUO)
The clinician is called upon often to deal with the problem of a patient with syncope or other neurologic symptoms, the etiology of which remains unexplained after a thorough medical and neurologic work-up. Such a work-up should include a detailed medical and pharmacologic history, pertinent blood chemistries and drug levels, neurologic consultation with appropriate studies, physical maneuvers including hyperventilation, carotid sinus massage, evaluation for orthostatic hypotension, maneuvers of the neck to evaluate the possibility of boney or atheromatous obstruction to cerebra1 blood flow, and prolonged ECG (Holter monitoring). Patients who “pass” this noninvasive workup may be designated as having “syncope of unknown
Present implantable defibrillators consist of a transvenous electrode introduced into the superior vena cava, and an extrapericardial elec-
POSITION
D. FISHER
TachyFunctkx
Rate
Fig. 25. Five position pacemaker code (Intersociety Commission on Heart Disease).W The original three position code has gained widespread acceptance, but the growth of programmability and antitachycardia pacing has led to the addition of two more positions. A conventional ventricular inhibited demand pacer would be coded as VVI: the addition of multiprogrammability would render it a VVLMO: A burst pacing capability for treatment of tachycardia would change the designation to VVLMB. (This illustration will soon be published simultaneously in several journals. Used here by permission of authors and PACE).
ELECTROPHYSIOLOGIC
77
TESTING
origin,” and may be appropriate candidates for electrophysiologic testing. Patients who meet this definition of SUO and who are found to have a prolongation of the H-V interval appear to benefit from permanent pacing.‘85 It is possible to induce supraventricular tachycardias in approximately 24% of patients with SUO (Table 7) .448 While supraventricular tachycardias can result in sudden hypotension and syncope, the 12% rate of tachycardia induction in a control group (Table 7) suggests the possibility of a significant number of false positive tests among SUO subjects. Ventricular tachycardia also can be induced in about a quarter of patients with SUO (Table S), but only in 0.7%-4.8% of Induction of ventricular tachycarcontrols.380*38’ dia thus constitutes a significant finding during electrophysiologic testing. A recent seriesof 92 patients with syncope of unknown origin, the majority of whom had Holter monitoring, exercise testing, and neurologic examinations, but not baseline carotid sinus massage,suggestedthat electrophysiologic testing could establish the probable cause of syncope in approximately 64%.448Of these 92 patients, 11 were found to have carotid sinus hypersensitivity, 10 ventricular arrhythmias, 9 supraventricular arrhythmias, and 5 sinus node dysfunction. The 54 patients in whom a causefor syncope was determined on the basisof electrophysiologic tests were treated accordingly, and after being followed up for 14.2 mo, 38 patients (89%) remained free of further syncope, and 2 patients had been improved. Electrophysiologic testing may not be able to help in the diagnosisof syncope due to intermittent profound hypervagotonia, sudden withdrawal of sympathetic tone,450and some other dynamic or intermittent states, such as prolonged Q-T interval syndromes and coronary artery spasm. Some patients with grand ma1 seizures may have normal neurologic examinations and thus escapeidentification. For many of these conditions, the importance of a detailed history and physical examination and prolonged
ECG monitoring are vital in making the diagnosis. OVERVIEW
The present role of clinical electrophysiologic testing is somewhat different from that anticipated a decade ago. Early hopes that simple sinus node function tests and the measurement of conduction intervals would provide reliable guidelines for the implantation of permanent pacemakers have been dashed on the rocks of complexity. Although progress has been made, accurate assessmentof risk in patients with suspected bradycardia remains an elusive goal. Stunning advances have been made in the diagnosis and treatment of tachycardias. Electrophysiologic testing has permitted detailed characterization of many tachycardias, and has identified previously unsuspectedmechanisms.Some of this information is directly translatable for use as guidelines by the clinical cardiologist. Electrophysiologic studies have permitted a quantum leap in the treatment of tachycardias in four important ways: (1) Analysis of the electrophysiologic characteristics of a tachycardia aids in assessingthe risk to the patient and in identifying possible“weak links” in the circuit to which pharmacologic or pacer therapy may be directed. (2) The technique of serial electrophysiologic pharmacologic testing provides a basis for an orderly and objective assessmentof drug efficacy. (3) The ability to reproducibly initiate and terminate tachycardias has resulted in the development of a rapidly increasing array of antitachycardia devices, some of which are implantable and operate automatically. (4) The effectiveness of antitachycardia surgery has been clearly enhanced by the use of preoperative and intraoperative ‘electrophysiologic studies. Electrophysiologic testing has appeared to have earned its place in the diagnostic and therapeutic repertoire. Investigators continue to be challenged by new concepts, findings, and applications for their technique, all of which promise continuing progressin the years to come.
REFERENCES 1. NarulaOS: His bundle Electrocardiography and Clinical Electrophysiology. Philadelphia, FA Davis, 1975 2. Krikler DM, Goodwin JF: Cardiac Arrhythmias: The Modern Electrophysiologic Approach. London, WB Saunders, 1975
3. Wellens HJJ, Lie Kl, Janse MJ: The Conduction System of the Heart. Structure, Function and Clinical implications. Philadelphia, Lea & Febiger, 1976 4. Kulbertus HE: Re-entrant Arrhythmias. Mechanisms and Treatment. Baltimore, University Park Press, 1977
78
JOHN
5. Narula OS: Cardiac Arrhythmias: Electrophysiology, Diagnosis and Management., Baltimore, Williams & Wilkins, 1979 6. Josephson ME, Seides SF: Clinical Cardiac Electrophysiology. Techniques and Interpretations. Philadelphia, Lea & Febiger, 1979 7. Series on Sudden Cardiac Death: Series on Cardiac Pacing. Prog in Cardiovasc Disease, Vol 23 and 24, 19801981 8. Fisher JD: Clinical Electrophysiologic Testing. Medication, Surgery, and Pacemakers for Arrhythmia Control, in Resnekov L, Julian D (eds): Friedberg: Diseases of the Heart (ed 4). New York, Churchill Livingston, (in press) 9. Flowers NC, Hand RC, Orander PC, et al: Surface recording of electrical activity from the region of the His bundle. Am J Cardiol 33:384-389, 1974 10. Berbari EJ, Lazzara R, El-Sherif N, et al: Extracardisc recordings of His-Purkinje activity during conduction disorders and junctional rhythms. Circulation 51:802-810, 1975
I 1. Furness A, Sharratt GP, Carson P: The feasibility of detecting His-bundle activity from the body surface. Cardiovast Res 9:390-396, 1975 12. Wajszczuk WJ, Stopczyk MJ, Moskowitz MS, et al: Noninvasive recordings of His-Purkinje activity in man by QRS-triggered signal averaging. Circulation 58:95-102, 1978
13. Fisher JD, Kay M, Mehra R, et al: Increased accuracy of the corrected H-V time, in Meere (ed): Proceedings of the VI World Symposium on Cardiac Pacing. Montreal, Pacesymp, 1979 14. Decaprio V: Endocardial electrograms from transvenous pacemaker electrodes. PhD Dissertation. Polytechnic Institute of Brooklyn. University Microfilms, 1977 15. Damato AN, Lau SH, Helfant RH, et al: Study of atrioventricular conduction in man using electrode catheter recordings of His bundle activity. Circulation 39:287-296, 1969 16. Damato AN, Lau SH, Helfant RH, et al: A study of heart block in man using His bundle recordings. Circulation 391297,
1969
17. Narula OS, Cohen LS, Samet P, et al: Localization of A-V conduction defects in man by recording of the His bundle electrogram. Am J Cardiol 25:228, 1970 18. Gallagher JJ, Damato AN, Lau SH, et al: Antecubital vein approach for recording His bundle activity in man. Am Heart J 85:199-204, 1973 19. Narula OS, Runge M, Samet P: A new catheter technique for His bundle recordings via the arm veins. Br Heart J 45:1226, 1973 20. Josephson ME, Seides SF: Electrophysiologic investigation: technical aspects, in Josephson ME, Seides SF (eds): Clinical Cardiac Electrophysiology: Techniques and Interpretations. Philadelphia, Lea & Febiger, 1979, p 17-18 21. Escher DJW, Furman S, Fisher JD, et al: Temporary pacing in the treatment of arrhythmias, in Watanube Y (ed): Cardiac Pacing. Proceedings of the V International Symposium, Tokyo. Amsterdam, Excerpta Medica, 1977, pp 153161 22. Fisher JD: His bundle studies during pullout of standard temporary pacing leads. Clin Res 25:648A, 1977
0. FISHER
23. Meister SG, Banka VS, Chadda KD, et al: A balloon tipped catheter for obtaining His bundle electrograms without 24. Moore EN, Spear JF: Effect of autonomic activity on pacemaker function and conduction, in Wellens, Lie, Janse (eds): The Conduction System of the Heart. Philadelphia, Lea & Febiger, 1976, pp IO&l 10 25. Martin P: The influence of the parasympathetic nervous system on atrioventricular conduction. Circ Res 411593-599,
1977
Jewel1 GM, Magorien RD, manic tone of patients during an terization. Am Heart J 99:51-57, 27. Dhingra RC, Rosen KM, conduction intervals and responses His bundle recording and atria1 26.
Schaael SF, et al: Autonoelectrophysiological cathe1980 Rahimtoola SH: Normal in sixty-one patients using pacing. Chest 64:55-59,
1973 28. Narula OS, Scherlag BJ, Samet P: Pervenous pacing of the specialized conducting system in man. Circulation 41:77, 1970 29. Narula OS: Validation of His bundle recordings: Limitations of the catheter technique in Narula OS (ed): His Bundle Electrocardiography and Clinical Electrophysiology. Philadelphia, FA Davis, 1975, pp 65-93 30. Narula OS: Longitudinal dissociation in the His bundle. Bundle branch block due to asynchronous conduction within the His bundle in man. Circulation 56:996-1006, 1977 3 1. El-Sherif N, Amat-Y-Leon F, Schonfield C: Normalization of BBB patterns by distal His bundle Pacing:Clinical and experimental evidence of longitudinal dissociation in the pathologic His bundle. Circulation 57:473483, 1978 32. Scheinman MM, Peters RW, Modin G, et al: Prognostic value or infranodal conduction time in patients with chronic bundle branch block. Circulation 56:240-244, 1977 33. McAnulty JH, Rahimtoola Sh, Murphy ES, et al: A prospective study of sudden death in “high-risk” bundlebranch block. N Engl J Med 299:209-215, 1978 34. Altschuler H, Fisher JD, Furman S: Significance of isolated H-V interval prolongation in symptomatic patients without documented heart block. Am Heart J 97: 19, 1979 35. Dhingra RC, Denes P, Wu D, et al: Prospective observations in patients with chronic bundle branch block and market H-V prolongation. Circulation 53:60@-604, 1976 36. Rosen KM, Rahimtoola SH, Chuquimia R, et al: Electrophysiological significance of first degree atrioventricular conduction disturbance. Circulation 43:491, 1971 37. Goldreyer BN, Weiss MB, Damata AN: Supraventricular tachycardia initiated by sinus beats. Circulation 44:830, 38.
197 1
Naruia OS: Electrophysiology of normal impulse propagation, in Narula OS (ed): Cardiac Arrhythmias, Electrophysiology, Diagnosis and Management. 1979, pp 57-65 39. Weiss S. Baker JP: The carotid sinus reflex in health and disease. Its role in the causation of fainting and convulsions. Medicine 12:297-354, 1933 40. Galdston M, Goldstein R, Steele MJ: Studies of the variation in circulatory and respiratory reponses to carotid sinus stimulation in man. Am Heart J 26:213-23 1, 1943 41. Sigler LH: Clinical observations on the carotid sinus
ELECTROPHYSIOLOGIC
TESTING
reflex 1. The frequency and the degree of response to carotid sinus pressure under various diseased states. Am J Med Sci 186:11(rllS, 1933 42. Sigler LH: Clinical observations on the carotid sinus reflex. II. The response to carotid sinus pressure at various ages and heart rates and rhythms. Am J Med Sci 186:118125,1933 43. Sigler LH: Further observations on the carotid sinus reflex. Ann Intern Med 9:1380-1392, 1936 44. Heidorn GH, McNamara AP: Effect of carotid sinus stimulation on the electrocardiograms of clinically normal individuals. Circulation 14:1104-l 113, 1956 45. Sigler LH: The cardioinhibitory carotid sinus reflex. Its importance as a vagocardiosensitivity test. Am J Cardiol 12:175-183,1963 46. Hartzler GO, Maloney JD: Cardioinhibitory carotid sinus hypersensitivity. Intracardiac recordings and clinical assessment. Arch Intern Med 137:727-731, 1977 47. Davies AB, Stephens MR. Davies AG: Carotid Sinus Hypersensitivity in patients presenting with syncope. Br Heart J 42:583-586, 1979 48. Fisher JD, Katz G, Furman S, et al: Differential responses to carotid sinus massage in cardiac patients with and without syncope. Clin Res (in press) 49. Hutchinson EC, Stock JPP: The carotid-sinus syndrome. Lancet 2:445-449,1960 50. Stevenson CA: The use of roentgen therapy in the carotid sinus syndrome. Radiology 32:209, 1939 5 1. Voss DM, Magnin GE: Demand pacing and carotid sinus syncope. Am Heart J 79:544-547, 1970 52. Walter PF, Crawley IS, Dorney ER: Carotid sinus hypersensitivity and syncope. Am J Cardiol 42:396-403, 1978. 53. Chughtai AL, Yans J, Kwatra M: Carotid sinus syncope. JAMA 237:2320, 1977 54. Cohen MV: Ventricular fibrillation precipitated by carotid sinus pressure: Case report and review of the literature. Am Heart J 84:681-686, 1972 55. Alexander S, Ping WC: Fatal ventricular fibrillation during carotid sinus stimulation. Am J Cardiol 18:2899291, 1966 56. Jonas EA, Kosowsky BD, Ramaswamy K: Complete His-Purkinje block produced by carotid sinus massage. Report of a case. Circulation 50:192-197, 1974 57. Narula OS: Disorders of sinus node function, in Narula OS (ed): Electrophysiologic Evaluation. His Bundle Electrocardiography and Clinical Electrophysiology. Philadelphia, FA Davis, 1975, pp 275-3 11 58. Lown B, Levine SA: The carotid sinus. Clinical value of its stimulation. Circulation 23:766-788, 1961 59. Bakst A, Goldberg B, Schamroth L: Significance of exercise-induced second degree atrioventricular block. Br Heart J 37:984986, 1975 60. Fisher JD: Unpublished Data 61. Tilkian Ag, Guilleminault C, Schroeder JS, et al: Sleep-induced apnea syndrome: Prevalence of cardiac arrhythmias and their reversal after tracheostomy. Am J Med 63:348-358, 1977 62. Kerin NZ, Edelstein J, Goldberg LB, et al: Cardiac dysrhythmias associated with obesity and sleep apnea. Cardiovasc Med 4:1167-l 172, 1979
79 63. Engel GL: Sudden and rapid death during psychological stress. Folk lore or folk wisdom. Ann Intern Med 74:771782,197l 64. Narula OS: Electrophysiology of normal impulse propagation, in Narula OS (ed): Cardiac Arrhythmias: Electrophysiology, Diagnosis and Management. Baltimore, Williams & Wilkins, 1979, p 57 65. Narula OS: Current concepts of atrioventricular block, Narula OS (ed): His Bundle Electrocardiography and Clinical electrophysiology. Philadelphia, FA Davis, 1975, p 139 66. Goodman LS, Gilman A: The Pharmacological Basis of Therapeutics (ed 6): New York, Macmillan, 1980 67. Lucchesi BR: Antiarrhythmic drugs: Key references. Circulation 59:1076-1078, 1979 68. Bigger JT Jr, Dresdale RJ, Heissenbuttel RH, et al: Ventricular arrhythmias in ischemic heart disease: Mechanism, prevalence, significance and management. Prog Cardiovasc Dis19:255-300, 1977 69. Singh BN, Collett JT, Chew CYC: New perspectives in the pharmacologic therapy of cardiac arrhythmias. Prog Cardiovasc Dis 22:243-301, 1980 70. Singh BN, Hauswirth 0: Comparative mechanisms of action of antiarrhythmic drugs. Am Heart J 87:367-382, 1974 7 1. Rosen MR, Wit AL, Hoffman BF: Electrophysiology and pharmacology of cardiac arrhythmias. Am Heart J Vol 88-90, 1974-1975 72. Zipes DP, Troup PJ: New antiarrhythmic agents: Am J Cardiol41:1005, 1978 73. Singh BN, Hauswirth 0: Comparative mechanisms of action of antiarrhythmic drugs. Am Heart J 87:367-382, 1974 74. Sami M, Mason JW, Peters F, et al: Clinical electrophysiologic effects of encainide, a newly developed antiarrhythmic agent. Am J Cardiol44:526-532, 1979 75. Sami M, Mason JW, Oh G, et al: Canine electrophysiology of encainide, a new antiarrhythmic drug. Am J Cardiol43:114991154, 1979 76. Bussmann W-D, Muller E, Hanel H-J, et al: Orally administered prajmalium bitartrate in acute and chronic ventricular arrhythmias. Am J Cardiol41:577-583, 1978 77. Fenici R, Marchei M, Bellocci F, et al: Effect of bunaphtine on right atria1 repolarisation in man. Br Heart J 39:787-794, 1977 78. Wellens HJJ, Bar FW, Gorgels AP, et al: Use of ajmaline in patients with the Wolff-Parkinson-White syndrome to disclose short refractory period of the accessory pathway. Am J Cardiol45:130-133, 1980 79. Gould L, Reddy CVR, Oh K-C, et al: Electrophysiologic properties of steroids in man. Curr Concept Pacing 1:6-17. 1978 80. Whipple GH: Papaverine as an antiarrhythmic agent. Angiology 28:737-749, 1977 8 1. Fowler NO, McCall D, Chou T-C, et al: Electrocardiographic changes and cardiac arrhythmias in patients receiving psychotropic drugs. Am J Cardiol 37:223-230, 1976 82. Gettes LS: On the classification of antiarrhythmic drugs. Modern Conept Cardiovasc Dis 48: 13-l 8, 1979
80 83. Gettes LS: The electrophysiologic effects of antiarrhythmic drugs. Am J Cardiol28:526-535, I97 1 84. Rosen MR, Hoffman BF: Mechanisms of action of antiarrhythmic Drugs. Circ Res 32:l-8, 1973 85. Harrison DC, Meffin PJ, Winkle RA: Clinical pharmacokinetics of antiarrhythmic drugs. Prog Cardiovasc Dis 20:217-242, 1977 86. Bigger JT Jr: Pharmacologic and clinical control of antiarrhythmic drugs. Am J Med 58:479-488, 197.5 87. Gibaldi M, Perrier D: Pharnacokinetics, in Swarbrick J (ed): Drugs and the Pharmaceutical Sciences, Vol 1. New York, Marcel Dekker, 1975 88. Greenblatt DJ, Bolognini V, Koch-Weser J, et al: Pharmacokinetic approach to the clinical use of lidocaine intravenously. JAMA 236:273-277, 1976 89. Wellens HJJ, Bar FWHM, Lie KI, et al: Effect of procainamide, propranolol, and verapamil on mechanism of tachycardia in patients with chronic recurrent ventricular tachycardia. Am J Cardiol40:579-585, 1977 90. Ferrer MI: The Sick Sinus Syndrome. New York, Futura, 1974 91. Narula OS: Sick sinus syndrome: Key References. Circulation 60:1422-1424, 1979 92. Scarpa WJ: The sick sinus syndrome. Am Heart J 92:648-660, 1976 93. Seinfeld D, Altschuler H, Yipintsoi T, et al: Pathogenetic locus of the sick sinus syndrome. Clin Res 26:270A, 1978 94. Jordan JL, Yamaguchi I, Mandel WJ: Studies on the mechanism of sinus node dysfunction in the sick sinus syndrome. Circulation 57:217-222, 1978 95. Mandel W, Hayakawa H, Danzig R, et al: Evaluation of sinoatrial node function in man by overdrive suppression. Circulation 44:59-66, 1971 96. Mandel WJ, Laks MM, Orayashi K: Sinus node function. Evaluation in patients with and without sinus node disease. Arch Intern Med 135:388-394, 1975 97. Lassers BW: First year follow-up after recovery from acute myocardial infarction with complete heart block. Lancet 2: I 172, 1969 98. Strauss HC, Bigger JT Jr, Saroff AL, et al: Electrophysiologic evaluation of sinus node function in patients with sinus node dysfunction. Circulation 53:763, 1976 99. Engel TR, Bond RC, Schaal SF: First-degree sinoatria1 heart block: Sinoatrial block in the sick-sinus syndrome. Am Heart J 3: 303-3 10, I976 100. Dhingra RC, Amat-Y-Leon F, Wyndham C, et al: Clinical significance of prolonged sinoatrial conduction time. Circulation 55:8-15, 1977 101. Kulbertus HE, De Leval-Rutten D, Mary L, et al: Sinus node recovery time in the elderly. Br Heart J 37:420425, 1975 102. Breithardt G, Seipel L, Loogen F: Sinus node recovery time and calculated sinoatrial conduction time in normal subjects and patients with sinus node dysfunction. Circulation 56:43-50, 1977 103. Gupta PK. Lichstein F, Chada KD, et al: Appraisal of sinus nodal recovery time in patients with sick sinus syndrome. Am J Cardiol 34:265-270, 1974 104. Crook B, Kitson D, McComish M, et al: Indirect measurement of sinoatrial conduction time in patients with
JOHN
D. FISHER
sinoatrial disease and in controls. Br Hear& J 39:771-777, 1977 105. Fisher JD, Seinfeld D: Sinus node recovery times and sino atrial conduction times in subjects with and without sick sinus syndrome. Unpublished data 106. Josephson ME, Seides SF: Sinus Node Function. Clinical Cardiac Electrophysiology: Techniques and Interpretations. Philadelphia, Lea & Febiger, 1979, pp 6 l-78 107. Altschuler H, Fisher JC: Increasing the yield of the sinus recovery time in the sick sinus syndrome. Clin Res 24:205A, 1976 108. Benditt DG, Strauss HC, Scheinman MM, et al: Analysis of secondary pauses following termination of rapid atrial pacing in man. Circulation 54:436-441, 1976 109. Miller HC, Strauss HC: Measurement of sinoatrial conduction time by premature atria1 stimulation in the rabbit. Circ Res 35:935-947, 1974 110. Nishi K, Yoshikawa Y, Tokenaka F, et al: Electrical activity of sinoatrial node cells of the rabbit surviving a long exposure to cold Tyrode’s solution. Circ Res 41:242-247, 1977 I1 1. Cramer M, Hariman RJ, Boxer R, et al: Electrograms from the canine sinoatrial pacemaker recorded in vitro and in situ. Am J Cardiol42:939-946, 1978 112. Mackintosh AF, English MJ, Vincent R, et al: Low voltage electrical activity preceding right atrial depolarisation in man. Br Heart J 42:117-123, 1979 113. Breithardt G, Seipel L: Effect of premature atrial depolarizations on sinus node automaticity in man. Circulation 53:92%925, 1976 114. Steinbeck G, Luderitz B: Sinoatrial pacemaker shift following atrial stimulation in man. Circulation 56:402-409, 1977 I1 5. Narula OS, Shantha N, Vasquez M, et al: A new method for measurement of sinoatrial conduction time. Circulation 58:706-714, 1978 116. Breithardt G, Seipel L: Comparative study of two methods of estimating sinoatrial conduction time in man. Am J Cardiol42:965-972, 1978 117. Dhingra RC, Wyndham C, Amat-Y-Leon F, et al: Sinus nodal responses to atrial extrastimuli in patients without apparent sinus node disease. Am J Cardiol 36:445452, 1975 118. Billette J, Bonin JP: Acute ischemic sinus node dysfunctions in dogs. Pace 1:313,326, 1978 119. Parameswaran R, Ohe T, Goldberg H: Sinus node dysfunction in acute myocardial infarction. Br Heart J 38:93-96.1976 120. Altschuler H, Seinfeld D, Fisher JD: Unpredictability of site of conduction injury due to acute myocardial infarction. Circulation 55-56 (Suppl III): 220, 1977 (abstr) 121. Jordan J, Yamaguchi I, Mandel WJ: Characteristics of sinoatrial conduction in patients with coronary artery disease. Circulation 55:569--574, 1977 122. Brown KA, Maloney JD, Smith HC, et al: Carotid sinus reflex in pts undergoing coronary angiography: Correlation of degree and location of CAD with response to CSM. Circulation 62:697-703, 1980 123. Dhingra RC, Amat-Y-Leon F, Wyndham C, et al: Electrophysiologic effects of atropine on sinus node and
ELECTROPHYSIOLOGIC
atrium
in patients
81
TESTING
with sinus node dysfunction.
Am J Cardiol
38:848-855,1976
124. Reiffei JA, Bigger JT Jr, Giardina EGV: “Paradoxical” prolongation of sinus nodal recovery time after atropine in the sick sinus syndrome. Am J Cardiol 36:98-104, 1975 125. Dhingra RC, Deedwania PC, Cummings JM, et al: Electrophysiologic effects of lidocaine on sinus node and atrium in patients with and without sinoatrial dysfunction. Circulation 57:448-453, 1978 126. Seinfeld D, Altschuler H, Yipintsoi T, et al: Increasing the sensitivity of the sinus recovery time in the sick sinus syndrome. Clin Res 26:270A, 1978 127. Gann D, Tolentino A, Samet P: Electrophysiologic evaluation of elderly patients with sinus bradycardia. Ann Intern Med 90:24-29, 1979 128. Evans TR, Callowhill EA, Krikler DM: Clinical value of tests of sino-atrial function. Pace l:2-7, 1978 129. Josephson ME, Scharf DL, Kastor JA, et al: Atrial endocardial activation in man: Electrode catheter technique for endocardial mapping. Am J Cardiol 39:972-981, 1977 130. Josephson ME, Scharf DL, Kastor JA, et al: Atrial endocardial activation in man: Electrode catheter technique for endocardial mapping. Am J Cardiol 39:972-98 I, 1977 131. Masuda SMO, De Carvalho AP: Sinoatrial transmission and atrial invasion during normal rhythm in the rabbit heart. Circ Res 37:414421, 1975 132. James TN: The connecting pathways between the sinus node and AV node and between the right and left atrium in the human heart. Am Heart J 66:498-508, 1963 133. Sherf L: The atrial conduction system: Clinical implications. Am J Cardiol37:8 I448 17, 1976 134. Ross AM, Proper MC, Aronson AL: Sinoventricular conduction in atrial standstill. J Electrocardiol9:161, 1976 135. Waldo AL, MaClean WAH, Karp RB, et al: Sequence of retrograde atrial activation of the human heart: Correlation with P wave polarity. Br Heart J 39:634-640, 1977 136. Aranda J, Castellanos A, Moleiro F, et al: Effects of the pacing site on A-H conduction and refractoriness in patients with short P-R intervals. Circulation 53:33-39, 1976 137. Amato JJ, Khan A, Payne D, et al: Pacemaker implantation in infants and children, in Meere C (ed): Proceedings of the Sixth World Symposium on Cardiac Pacing. Montreal, Pacesymp 1979 138. Batsford WP, Akhtar M, Caracta A, et al: Effect of atria1 stimulation site on the electrophysiological properties of the atrioventricular node in man. Circulation 50:283-292, 1974 139. Anderson RH, Becker AE. Wenink ACG, et al: The development of the cardiac specialized tissue, in Wellens HJJ, Lie KI, Janse MJ (eds): The Conduction System of the Heart: Structure, Function and Clinical Implications. Philadelphia, Lea & Febiger, 1976 140. Gelband H, Bush H, Rosen M, et al: Electrophysiologic properties of isolated preparations of human atria1 myocardium. Circ Res 30:293. 1972 141. Hordof AJ, Edie R, Malm JR, et al: Electrophysiologic properties and response to pharmacologic agents of fibers from diseased human atria. Circulation 54:774-779, 1976 142. Giusti RP, Fisher JD: Prolongation of intra-atrial
conduction time in response to atrial pacing. Clin Res 24:218A, 1976 143. Millar RNS, Mauer BJ, Rei DS, et al: Studies of intra-atrial conduction with bipolar atrial and His electrograms. Br Heart J 35:604-609, I973 144. Waldo Al, Bush HL, Gelband H, et al: Effects canine F Wave of discrete lesions in the specialized tracts, Circ Res 29:452, 1971
on the atrial
145. Scherlag BJ, Yeh BK, Robinson MJ: Inferior atrial pathway in the dog. Circ Res 31:18, 1972
inter-
146. Leier CV, Jewel1 GM, Magorien RD, et al: Interatrial conduction (activation) times. Am J Cardiol 44:442446.1979 147. Fishman D, Moran JF, Randall W, et al: Effect of left sympathetics on AV nodal conduction properties. Clin Res 25:22lA, 1977 148. Hageman CR, Goldberg JM, Armour JA, et al: Cardiac dysrhythmias induced by autonomic nerve stimulation. Am J Cardiol 32:823-830, 1973 149. Brodsky M, Wu D, Denes P, et al: Arrhythmias documented by 24-hour continuous ECG monitoring in 50 male medical students without apparent heart disease. Am J Cardiol 39:390-395, 1977
150. Meytes 1, Kaplinsky E, Yakini JH, et al: Wenckebath AV block: A frequent feature following heavy physical training. Am Heart J 90:426-430, 1975 I5 1. Young D, Eisenberg RE, Fish B, et al: Wenckebach AV block (Mobitz type 1) in children and adolescents. Am J Cardiol40:383-388, 1977 152. Janse MJ, Van Capelle FJL, Anderson RH, et al: Electrophysiology and structure of the atrioventricular node of the isolated rabbit heart, in Wellens HJJ, Lie KI, Janse MJ: The Conduction System of the Heart: Structure, Function and Clinical Implications. Philadelphia, Lea & Febiger, 1976 153. Pahlajani DB, Muller RA, Serratto M: Patterns of AV conduction in children. Am Heart J 90:165-171, 1975 1.54. Billette J, Bonin JP: Rate-induced shortenings in refractory periods and conduction time in the dog atrioventricular node. in Meere C (ed): Proceedings of the Vlth World Symposium on Cardiac Pacing, Pace Symp, Montreal. 1979, chap 1 l-4 155. Bharato S, Dhingra RC, Lev M, et al: Conduction system in a patient with Prinzmetals’ angina and transient AV block. Am J Cardiol 39:120-125, 1977 156. Anderson RH, Wenick ACG, Losekoot TG, et al: Congenitally complete heart block. Developmental aspects. Circulation 56:90-101, 1977 157. Narula man: Response parasympathetic
OS, Narula JT: Junctional pacemakers in to overdrive suppression with and without blockade. Circulation 57:88&889, 1978
158. Dhingra RC, Wyndham C, Amat-Y-Leon F, et al: Significance of A-H interval in patients with chronic bundle branch block: Clinical, electrophysiologic and follow-up observations. Am J Cardiol 37:231-236, 1976 159. Dhingra RC, Wyndham C. Bauernfeind R, et al: Significance of block distal to the His bundle induced by atrial pacing in patients with chronic bifascicular block. Circulation 60:1455-1465, 1979 160. Castillo
C, Castellanos
A Jr: Retrograde
activation
82
of the His bundle in the human heart. Am J Cardiol 27:264-271,197l 161. Josephson ME, Kastor JA: His-Purkinje conduction during retrograde stress. J Clin Invest 61:171-177, 1978 162. Akbtar M, Gilbert Cj, Wolf FG, et al: Retrograde conduction in the His-Purkinje system: Analysis of the routes of impulse propagation using His and right bundle branch recordings. Circulation 59:1252-1265, 1979 163. Josephson ME, Caracta AR, Ricciutti MA, et al: Electrrophysidogic properties of procainamide in man. Am J Cardiol 33596-603, 1974 164. Cannom DS: The effects of procaine amide in left bundle branch block. Circulation 51-52 (Suppl II):137, 1975 165. McKenna WJ, Rowland E, Davies J, et al: Failure to predict development of atrioventricular bloc with electrophysiological testing supplemented by ajmaline. Pace 3:666669,198O 166. Gupta PK, Lichstein E, Chauda KD: Lidocaineinduced heart block in patients with bundle branch block. Am J Cardiol 33:487-492, 1974 167. Narula OS, Samet P: Predilection of elderly females for intra-His bundle (BH) blocks. Circulation 49-50 (Suppl 111):395, 1974 168. Narula OS, Samet P: Wenckebach and Mobitz type II A-V block due to block within the His bundle and bundle branches. Circulation 4 I :947-965, 1970 169. Gupta PK, Lichstein E, Chada KD: Chronic His bundle block: Clinical, electrocardiographic, electrophysiological, and follow-up studies on 16 patients. Br Heart J 38:1343-1349,1976 170. Bharatii S, Lev M, Wu D, et al: Patbophysiologic correlations in two cases of split His bundle potentials. Circulation 49:615-623, 1974 17 1. Nasrallah AT, Gillette PC, Mullins CE: Congenital and surgical atrioventricular block within the His bundle. Am J Cardiol 36:9 14-920, 1975 172. McAnulty JH, Murphy E, Rohimtoola SH: A prospective evaluation of intrahisian conduction delay. Circulation 59:1035-1039, 1979 173. Dhingra RC, Denes P, Wu D, et al: Prospective observations in patients with chronic bundle branch block and marked H-V prolongation. Circulation 53:600-604, 1976 174. Rosen KM, Dhingra RC, Wyndham CRC, et al: Significance of HV interval in 515 patients with chronic bifascicular block. Am J Cardiol45:405, 1980 175. Narula OS: Intraventricular conduction defects: Current concepts and clinical significance, in Narula OS (ed): Cardiac Arrhythmias: Electrophysiology, Diagnosis and Management. Baltimore, Williams & Wilkins, 1979, p 114 176. Denes P, Dhingra RC, Wu D: H-V interval in patients with bifascicular block (right bundle branch block and left anterior hemiblock). Clinical, electrocardiographic, and electrophysiologic correlation. Am J Cardiol 35:23-29, 1975 177. Scheinman MM, Peters RW, Brennan M, et al: Prognostic value of infranodal conduction time in patients with chronic bundle branch block. Circulation 56:240-245, 1977 178. Denes P, Dhingra RC, Wu D, et al: Sudden death in
JOHN
D. FISHER
patients with chronic bifascicular block, Arch Intern Med 137:1005-1010,1977 179. Gupta PK, Licbstein E, Chadda KD: Fol!ow-up studies in patients with right bundle branch block and left anterior hemiblock: Significance of H-V interval. J Electrocardiol lO:221-224, 1977 180. McAnulty JH, Rahimitcola SH, Murphy ES, et al: A prospective study of sudden death in “high-risk” bundlebranch block. N Engl J Med 299:209-215, 1978 181. Dhingra RC, Wyndham C, Amat-Y-Leon F, et al: Incidence and site of atrioventricular block in patients with chronic bifascicular block. Circulation 59:238-246, 1979 182. Peters RW, Scheinman MM, Modin G, et al: Prophylactic permanent pacemakers for patients with chronic bundle branch block. Am J Med 66:978-985, 1979 183. Scbeinman M, Weiss A, Kunkel F: His bundle recordings in patients with bundle branch block and transient neurologic symptoms. Circulation 48:322-330, 1973 184. Vera Z, Mason DT, Fletcher RD, et al: Prolonged His-Q interval in chronic bifascicular block. Relation to impending complete heart block. Circulation 53:46, 1976 185. Altschuler H, Fisher JD, Furman S: Significance of isolated H-V interval prolongation in symptomatic patients without documented heart block. Am Heart J 97:19, 1979 186. Surawicz B: Prognosis of patients with chronic bifascicular block (editorial and review). Circulation 60:4&42, 1979 187. Dhingra RC, Wyndham C, Bauernfeind R, et al: Significance of chronic bifascicular block without apparent organic heart disease. Circulation 60:33-39, 1979 188. Kulbertus HE, De Leval-Rutten F, Dubois M, et al: Prognostic significance of left anterior bemiblock with right bundle branch block in mass screening. Am J Cardiol 41:385, 1978 (abstr) 189. McAnulty JH, Kauffman, S, Murphy E: Survival in patients with intraventricular conduction defects. Arch Intern Med 138:30-35, 1978 190. Dhingra RC, Amat-Y-Leon F, Wyndham C, et al: Significance of left axis deviation in patients with chronic left bundle branch block. Am J Cardiol42:551-556, 1978 191. Narula OS, Samet P: Right bundle branch block with normal, left or right axis deviation: Analysis by His bundle recordings. Am J Med 51:432455, 1971 192. Levites R, Haft JL: Significance of first degree heart block (prolonged PR interval) in bifascicular block. Am J Cardiol34:259-264, 1974 193. Castellanos A Jr: Letters to the editor: H-V intervals in LBBB. Circulation 47: I1 33-1134, 1973 194. Rosen KM: H-V intervals in LBBB. Circulation 47:1134, 1973 195. Wu D, Denes P, Dhingra R, et al: Bundle branch block: Demonstration of the incomplete nature of some “complete” bundle branch and fascicular blocks by the extrastimulus technique. Am J Cardiol 33:583-589, 1974 196. Lichstein E, Mahapatra R, Gupta PK, et al: Significance of complete left bundle branch block with left axis deviation. Am J Cardiol44:239-242, 1979 197. Tans AC, Lie KI, Durrer D: Clinical setting and prognostic significance of high degree atrioventricular block in acute inferior myocardial infarction: A study of 144 patients. Am Heart J 99:4-8, 1980 198. Biddle TL, Ehrich DA, Yu PN, et al: Relation of
ELECTROPHYSlOLOGlC
TESTING
heart block and left ventricular dysfunction in acute myocardial infarction. Am J Cardiol 39:961-966, 1977 199. Jones ME, Terry G, Kenmure ACF: Frequency and significance of conduction defects in acute myocardial infarction. Am Heart J 94:163-167, 1977 200. Ginks WR, Sutton R, Oh W, et al: Long-term prognosis after acute anterior infarction wth atrioventricular block. Br Heart J 39: 186-l 89, 1977 201. Hindham MC, Wagner GS, Jaro M: The clinical significance of bundle branch block complicating acute myocardial infarction. I. Clinical characteristics, hospital mortality, and one-year follow-up. Circulation 58:679-688, 1978 202. Hindham MC, Wagner GS, Jaro M: The clinical significance of bundle branch block complicating acute myocardial infarction. II. Indications for temporary and permanent pacemaker insertion. Circulation 58:.689-699, 1978 203. Godman MJ, Lassers BW, Julian DC: Complete bundle-branch block complicating acute myocardial infarction. N Engl J Med 282:237-240, 1970 204. Nimetz AA, Shubrooks SJ Jr, Hutter AM, et al: The significance of bundle branch block during acute myocardial infarction. Am Heart J 90:439-444, 1975 205. Waters DD, Mizgala HF: Long-term prognosis of patients with incomplete bilateral bundle branch block complicating acute myocardial infarction. Role of cardiac pacing, Am .I Cardiol 34: l-5, I974 206. Ritter WS, Atkins JM, Blumquist CG, et al: Permanent pacing in patients wtih transient trifascicular block during acute myocardial infarction. Am J Cardiol 38:205208, 1976 207. Norris RM, Croxson MS: Bundle branch block in acute myocardial infarction. Am Heart J 79:728-733, 1970 208. Scheinman M, Brenman B: Clinical and anatomic implications of intraventricular conduction blocks in acute myocardial infarction. Circulation 46:753-760, 1972 209. Lichstein E, Gupta PK, Chadda KD: Long-term survival of patients with incomplete bundle-branch block complicating acute myocardial infarction. Br Heart J 83:924-930, 1975 210. Lie KI, Wellens HJ, Schuilenburg RM, et al: Factors influencing prognosis of bundle branch block complicating acute antero-septal infarction. The value of His bundle recordings. Circulation 50:935-941, 1974 21 I. Gould L, Reddy CVR, Kim SG, et al: His bundle electrogram in patients with acute myocardial infarction. Pace 2:428-434, 1979 212. Harper R, Hudt D, Vohra J, et al: His bundle electrogram in patients with acute myocardial infarction complicated by atrioventricular or intraventricular conduction disturbances. Br Heart J 37:705-710, 1975 213. Buyukozturk K, Korkut F, Merit M, et al: Prognostic significance of isolated left anterior hemiblock and left axis deviation in the course of acute myocardial infarction. Br Heart J 39:1192-l 195, 1977 214. Rosenbaum MB, Yesuron J, Lazzari JO, et al: Left anterior hemiblock obscuring the diagnosis of right bundle branch block. Circulation 48:298-303, 1973 215. Sclarouskys S, Lewin RF, Strasberg B, et al: Left anterior hemiblock obscuring the diagnosis of right bundle
83 branch block in acute myocardial infarction. Circulation 60:26-32.1979 216. Fisher ML, Mugmon MA, Carliner NH, et al: Left anterior fascicular block: Electrocardiographic criteria for its recognition in the presence of inferior myocardial infarction. Am J Cardiol44:645-650, 1979 217. Rosen KM, Loeb HS, Chuquimia R, et al: Site of heart block in acute myocardial infarction. Circulation 42:925-933, 1970 218. Altschuler H, Seinfeld D, Fisher JD: Unpredictability of site of conduction injury due to acute myocardial infarction. Circulation 55-56(Suppl III): 220, 1977 (abstr) 219. Sinker D, Parameswaran R, Goldberg H: Sinus and A-V nodal dysfunction following myocardial infarction. J Electrocardiology 8:281-283, 1975 220. Nasrallah AT, Beard EF: Intra-His bundle block complicating acute inferior myocardial infarction. Chest 69:420-422,1976 221. Kosowsky BD, Latif P, Radoff AM: Multilevel 8‘trioventricular block. Circulation 54:914-921, 1976 222. Friedman HS, Zaman Q, Haft Jf, et al: Assessment of A-V conduction in aortic valve disease. Am J Cardiol 39:314, 1977 (abstr) 223. Dhingra RC, Amat-Y-Leon F, Pietras RJ, et al: Sites of conduction disease in aortic stenosis. Significance of valve gradient and calcification. Ann Intern Med 87:275280, 1977 224. Ritchie JL, Hammermeister KE, Kennedy JW: Refractory ventricular tachycardia and fibrillation in a patient with the prolapsing mitral leaflet syndrome: Successful control with overdrive facing. Am J Cardiol 37:314-316, 1976 225. Wei JY, Bulkley BH, Schaeffer AH, et al: Mitralvalve prolapse syndrome and recurrent ventricular tachyarrhythmias: A malignant variant refractory to conventional drug therapy. Ann Intern Med 89:6-9, 1978 226. Cosio FG, Moro C, Alonso M, et al: The Q waves of hypertrophic cardiomyopathy. An electrophysiologic study. N Engl J Med 302:96-99, 1980 227. Johnson AD, Daily PO: Hypertrophic subaortic stenosis complicated by high degree heart block: Successful treatment with an atrial synchronous ventricular pacemaker. Chest 671491-494, 1975 228. Probst P, Pachinger 0, Murad AA, et al: The HQ time in congestive cardiomyopathies. Ani Heart J 97:436441,1979 229. Luca C: Electrophysiological properties of right heart and atrioventricular conducting system in patients with alcoholic cardiomyopathy. Br Heart J 42:274-28 I, 1979 230. Bharati S, Lev M, Denes P: Infiltrative cardiomyopathy with conduction disease and ventricular arrhythmia: Electrophysiologic and pathologic correlations. J Cardiol 45:163%173, 1980 23 1. Vigorita VJ, Hutchins GM: Cardiac conduction system in hemochromatosis: Clinical and pathologic features of six patients. Am J Cardiol44:418-423, 1979 232. Wray R, Iveson M: Complete heart block and systemic lupus erythematosus. Br Heart J 37:982-983, 1975 233. McCue CM, Mantakas ME, Tingelstad JB, et al: Congenital heart block in newborns of mothers with connective tissue disease. Circulation 56:82-90, 1977 234. Winkler RB, Nora AH, Nora JJ: Familial congeni-
a4 tal complete heart block and maternal systemic lupus erythematosis. Circulation 56: 1 103-l 107, 1977 235. Fiddler GI, Campbell RWF, Pottage A, et al: Varicella myocarditis presenting with unusual ventricular arrhythmias. Br Heart J 39: I 150-I 153, 1977 236. Gann D, Narula OS, Kaplan S, et al: Complete heart block with gonococcal septicemia. Ann Intern Med 86:749750, 1977 237. Hernandez-Pieretti 0, Morales-Rocha J, Acquatella H, et al: Pacemaker inplantation in chronic Chagas’ heart disease complicated by Adams-Stokes Syndrome. Am J Cardiol46:114-I 17, 196.5 238. Rosenbaum MB, Alvarez AJ: The electrocardiogram in chronic chagesic myocarditis. Am Heart J 50:492, 1955 239. Wei JY, Genecin A, Greene HL, et al: Coronary spasm with ventricular fibrillation during thyrotoxicosis: Response to attaining euthyroid state. Am J Cardiol43:335339,1979 240. Gavrilescu S, Luca C, Streian C, et al: Monophasic action potentials of right atrium and electrophysiological properties of AV conducting system in patients with hypothyroidism. Br Heart J 38:135&1354, 1976 241. Greenspan AM, Camardo JS, Horowitz LN, et al: Strength-interval relations in human ventricle. Circulation 59-60 (Suppl II): 23, 1979 (abstr) 242. Denes P, Wu D, Dhingra R, et al: The effects of cycle length on cardiac refractory periods in man. Circulation 49:3241, 1974 243. Dubrow IW, Fisher EA, Amat-Y-Leon F, et al: Comparison of cardiac refractory periods in children and adults. Circulation 51:485491, 1975 244. Watanabe Y, Nishimura M: Terminology and electrophysiologic concepts in cardiac arrhythmias. V. Phase 3 block and phase 4 block. Part I. Pace 2:335, 1979 245. Watanabe Y, Nishimura M: Terminology and electrophysiologic concepts in cardiac arrhythmias. VI. Phase 3 block and phase 4 block. Part 2. Pace 2:624, 1979 246. El-Sherif N, Scherlag BJ, Lazarra R, et al: Pathophysiology of tachycardiaand bradycardia-dependent block in the canine proximal His-Purkinje system after acute myocardial ischemia. Am J Cardiol 33:540, 1974 247. Castellanos A, Khuddus SA, Sommer LS, et al: His bundle recordings in bradycardia-dependent AV block induced by premature beats. Br Heart J 37:570-575, 1975 248. Asha AS, Castellanos A Jr, Wells D, et al: Type I, type II, and type III gaps in bundle-branch conduction. Circulation 47:325-330, 1973 249. Wu D, Denes P, Dhingra R, et al: Nature of the gap phenomenon in man. Circ Res 34:682-692, 1974 250. Akhtar M, Damato AN, Batsford WP, et al: Unmasking and conversion of gap phenomenon in the human heart. Circulation 49:624-630, 1974 25 I. Akhtar M, Damato AN, Caracta AR, et al: The gap phenomena during retrograde conduction in man. Circulation 4981 l-817, 1974 252. Akhtar M, Caracta AR, Lau SH, et al: Demonstration of intra-atrial conduction delay, block, gap and reentry: A report of two cases. Circulation 58:947-955, 1978 253. Waleffe A, Bruninx P, Demoulin J-C, et al: Two unusual cases of intra-atrial gap. Br Heart J 39:451-455, 1977
JOHN
D. FISHER
254. Puech P, Guimond C, Nadeau R, et al: Supernormal conduction in the intact heart; in Narula OS (ed): Cardiac arrhythmias: Electrophysiology, Diagnosis and Management. Baltimore, Williams & Wilkins, 1979, pp 40-56 255. Childers RW: Supernormality, in: Complex Electrocardiography I. Philadelphia, FA Davis, 1973, pp 136-l 58 256. Cranefield PF, Wit AL, Hoffman BF: Genesis of cardiac arrhythmias. Circulation 47:190, 1973 257. Rosen MR, Danilo P Jr: The electrophysiological basis for cardiac arrhythmias, in Narula OS (ed): Cardiac Arrhythmias: Electrophysiology, Diagnosis and Management. Baltimore, Williams & Wilkins, 1979, pp 3-13 258. Vassalle M, Cummins M, Castro C, et al: The relationship between overdrive suppression and overdrive excitation in ventricular pacemakers in dogs. Circ Res 38367, 1976 259. Vassale M: The relationship among natural cardiac pacemakers. Overdrive suppression. Circ Res 41:269-277, 1977 260. Wit AL, Cranefield PF: Triggered activity in cardiac muscle fibers of the simian mitral valve. Circ Res 38:85-98, 1976 26 I. Watanabe Y: Terminology and electrophysiologic concepts in cardiac arrhythmias. III. Exit block, entrance block and protection block. Pace 1:498-509, 1978 262. Schamroth L: The pathogenesis and mechanism of ventricular arrhythmias, in Yu PN, Goodwin JF (eds): Progress in Cardiology, 3. Philadelphia, Lea & Febiger, 1974, p 75 263. Kupersmith J: Electrophysiologic mapping during open heart surgery. Prog Cardiovasc Dis 19: 167, 1976 264. Spielman SR, Michelson EL, Horowitz LN, et al: The limitations of epicardial mapping as a guide to the surgical therapy of ventricular tachycardia. Circulation 56:666-670,197s 265. Ideker RE, Smith WM, Wallace AG: A computerized method for the rapid display of ventricular activation during the intraoperative study of arrhythmias. Circulation 59:449%458,1979 266. Josephson ME, Horowitz LN, Farshidi A, et al: Recurrent sustained ventricular tachycardia. 2. Endocardial mapping. Circulation 57:440-447, 1978 267. Curry PVL, O’Keefe DB, Pitches D, et al: Localisation of ventricular tachycardia by a new technique: Pacemapping. Circulation 59-60 (Suppl II): 25, 1979 268. Josephson ME: Paroxysmal supraventricular tachycardia: An electrophysiologic approach. Am J Cardiol 41:1123-l 126, 1978 269. Narula OS: Sinus node re-entry. A mechanism for supraventricular tachycardia. Circulation 50:1114-l 128, 1974 270. Narula OS: Paroxysmal supraventricular tachycardia due to sinus node and intra-atrial reentry, in Narula OS (ed): Cardiac Arrhythmias: Electrophysiology, Diagnosis and Management. Baltimore Williams & Wilkins, 1979, pp 272-293 271. Wu D, Amat-Y-Leon F, Denes P, et al: Demonstration of sustained sinus and atrial re-entry as a mechanism of paroxysmal supraventricular tachycardia. Circulation 51:234-243, 1975 272. Bauernfeind RA, Amat-Y-Leon F, Dhingra RC, et
ELECTROPHYSIOLOGIC
85
TESTING
al: Chronic nonparoxysmal sinus tachycardia in otherwise healthy persons. Ann Intern Med 91:702-710, 1979 273. Tenczer J, Littmann L, Molnar F, et al: Atrial reentry in chronic repetitive supraventricular tachycardia. Am Heart J 99:349-353, 1980 274. Coumel P, Flammang D, Attuel P, et al: Sustained intra-atrial reentrant tachycardia. Electrophysiologic study of 20 cases. Clin Cardiol 2:167-178, 1979 275. Ogawa S, Dreifus LS, Osmick MJ: Longitudinal dissociation of Bachmann’s bundle as a mechanism of paroxysmal supraventricular tachycardia. Am J Cardiol 40:915922,1977 276. Maclean WAH, Karp RB, Kouchoukos NT, et al: P waves during ectopic atrial rhythms in man. A study utilizing atrial pacing with fixed electrodes. Circulation 52:426-434, 1975 277. Gillette PC, Garson A Jr: Electrophysiologic and pharmacologic characteristics of automatic ectopic atria1 tachycardia. Circulation 56:571-575, 1977 278. Goldreyer BN, Gallagher JJ, Damato AN: The electrophysiologic demonstration of atria1 ectopcic tachycardia in man. Am Heart J 85:205, 1973 279. Coumel P, Leclerq J-F, Attuel P: Automatic influences in the genesis of atria1 arrhythmias: Atrial flutter and fibrillation of vagal origin, in Narula OS (ed): Cardiac Arrhythmias: Electrophysiology, Diagnosis and management. Baltimore, Williams & Wilkins, 1979, pp 2433255 280. Waldo AL, Wells JL Jr, Plumb VJ, et al: Characterization of atrial flutter: Studies in patients following open heart surgery, in Narula OS (ed): Cardiac Arrhythmias: Electrophysiology, Diagnosis and Management. Baltimore, Williams & Wilkins, 1979, pp 256627 1 281. Waldo AL, Maclean WAH, Karp RB, et al: Entrainment and interruption of atrial flutter with atrial pacing: Studies in man following open heart surgery. Circulation 56:737-745, 1977 282. Denes P, Wu D, Amat-Y-Leon F, et nants of atrioventricular nodal re-entrance atrial stimulation in patients with dual A-V Circulation 56:253-259, 1977 283. Thapar MK, Gillette PC: Dual nodal pathways: A common electrophysiologic children. Circulation 60: 136991374, 1979
al: The determiwith premature nodal pathways. atrioventricular response
in
284. Josephson ME, Kastor JA: Paroxysmal supraventricular tachycardia: Is the atrium a necessary link? Circulation 54:430-435, 1976 285. Akhtar M, Damato AN, Batsford WP, et al: Induction of atrioventricular nodal reentrant tachycardia after atropine. Report of five cases. Am J Cardiol 36:286-291, 1975 286. Fabregas RA, Han J, Gael BG, et al: Facilitation of A-V nodal reciprocation by procainamide. Am Heart J 9 1:46&467, 1976 287. Sung RJ, Styperek JL, Myerburg RJ, et al: Initiation of two distinct forms of atrioventricular nodal reentrant tachycardia during programmed ventricular stimulation in man. Am J Cardiol 42:40&415, 1978 288. Wu D, Denes P, Amat-Y-Leon F, et al: An unusual variety of atrioventricular nodal re-entry due to retrograde dual atrioventricular nodal pathways. Circulation 56:50-59, I977
289. Wolff GS, Sung RJ, Pickoff A, et al: The fast-slow form of atrioventricular nodal reentrant tachycardia in childrenAmJCardiol43:1181-1188, 1979 290. Coumel P: Junctional reciprocating tachycardias. The permanent and paroxysmal forms of A-V nodal reciprocating tachycardias. J Electrocardiol 8:79-90, 1975 291. Coumel P, Attuel P, Leclerq LF: Permanent form of junctional reciprocating tachycardia: Mechanism, clinical and therapeutic implications, in Narula OS (ed): Cardiac Arrhythmias: Electrophysiology, Diagnosis and Management. Baltimore, Williams & Wilkins, 1979, pp 347-363 292. Csapo G: Paroxysmal nonreentrant tachycardias due to simultaneous conduction in dual atrioventricular nodal pathways. Am J Cardiol43:1033-1045, 1979 293. Garson A Jr, Gillette PC: Junctional ectopic tachycardia in children: Electrocardiography, electrophysiology and pharmacologic response. Am J Cardiol 44:298-302, 1979 294. Denes P, Kehoe R, Rosen KM: Multiple reentrant tachycardias due to retrograde conduction of dual atrioventricular bundles with atrioventricular nodal-like properties. Am J Cardiol44:162-170,1979 295. Ferrior MI: Preexcitation. Am J Med 62:715-729, 1977 296. Narula OS: Wolff-Parkinson White syndrome. A review. Circulation 47:872-887, 1973 297. Wolff GS, Han J, Curran J: Wolff-Parkinson-White syndrome in the neonate. Am J Cardiol41:559-563, 1978 298. Gillette PC, Garson A Jr, Kugler JD: Wolff-Parkinson-white syndrome in children: Electrophysiologic and pharmacologic characteristics. Circulation 60: 1487-1495, 1979 299. Gavrilescu S, Gavrilescu M, Luca C: Accelerated atrioventricular conduction during acute myocardial infarction. Am Heart J 94:21-27, 1977 300. Svenson RH, Miller HC, Gallagher JJ, et al: Electrophysiological evaluation of the Wolff-Parkinson-White syndrome. Circulation 52:552-562, 1975 301. Denes P, Wu D, Amat-Y-Leon F: Determinants of atrioventricular reentrant paroxysmal tachycardia in patients with Wolff-Parkinson-White syndrome. Circulation 58:415-425, 1978 302. Pritchett ELC, Gallagher JJ, Scheinman M, et al: Determinants of antegrade echo zone in the Wolff-Parkinson-white syndrome. Circulation 57:671-677, 1978 303. Sung RJ, Castellanos A, Mallon SM. et al: Mode of initiation of reciprocating tachycardia during programmed ventricular stimulation in the Wolff-Parkinson-White syndrome. Am J Cardiol40:24-31, 1977 304. Denes P, Wyndham CR, Amat-Y-Leon F, et al: Atrial pacing at multiple sites in the Wolff-Parkinson-White syndrome. Br Heart J 39:506-5 14, 1977 305. Tonkin AM, Miller HC, Svenson RH, et al: Refractory periods of the accessory pathway in the Wolff-Parkinson-white syndrome. Circulation 52:563-569, 1975 306. Gallagher JJ, Scaly WC, Kasell J, et al: Multiple accessory pathways in patients with preexcitation syndrome. Circulation 54:571, 1976 307. Narula OS: Retrograde pre-excitation. Comparison of antegrade and retrograde conduction intervals in man. Circulation 50:1129-l 143, 1974 308. Wellens HJJ, Durrer D: Patterns of Ventriculo-
86
atrial condnction in the Wolff-Parkinson-White syndrome. Circulation 49:22, 1974 309. Klein GJ, Prystowsky EN, Pritchett ELC, et al: Atypical patterns of retrograde conduction over accessory atriovenetricular pathways in the Wolff-Parkinson-White syndrome. Circulation 60: 1477-l 486, 1979 310. Zipes DP, De Joseph RL, Rothbaum DA: Unusual properties of accessory pathways. Circulation 49: 1200, 1974 3 11. Rosen KM: A-V nodal reentrance. An unexpected mechanism of paroxysmal tachycardia in a patient with preexcitation. Circulation 47: 1267-I 273, 1973 312. Spurrell RAJ, Krikler D, Sowton E: Two or more intra-AV nodal pathways in association with either a James or Kent extranodal bypass in 3 patients with paroxysmal supraventricular tachycardia. Br Heart J 35:113-122, 1973 313. Sung RJ, Styperek JL: Electrophysiologic identihcation of dual atrioventricular nodal pathway conduction in patients with reciprocating tachycardia using anomalous bypass tracts. Circulation 60:1464-1476, 1979 314. Przybylski J, Chiale PA, Halpern MS, et al: Existence of automaticity in anomalous bundle of Wolff-Parkinson-white syndrome. Br Heart J 40:672-680, 1978 315. James TN, Puech P: De subitaneis mortibus IX. Type A Wolf-Parkinson-White syndrome. Circulation 50:1264-1280.1974 316. Wellens HJ, Durrer D: Effect of digitalis on Atrioventricular conduction and circus-movement tachycardias in patients with Wolff-Parkinson-White syndrome. Circulation 47:1229-1233, 1973 317. Sellers DT, Bashore TM, Gallagher JJ: Digitalis in the pre-excitation syndrome: Analysis during atria1 fibrillation. Circulation 56:260-267, 1977 3 18. Dreifus LS, Wellens HJJ, Watanabe Y, et al: Sinus bradycardia and atrial fibrillation associated with WPW syndrome. Am J Cardiol 38: 149, 1976 319. Campbell RWF, Smith RA, Gallagher JJ, et al: Atrial fibrillation in the preexcitation syndrome. Am J Cardiol40:514-520, 1977 320. Klein GJ, Bashore TM, Sellers TD, et al: Ventricular fibrillation in the Wolff-Parkinson-White syndrome. N Engl J Med 301:108~1085,1979 321. Sung RJ, Castellanos A, Mallon SM: Mechanisms of spontaneous alternation between reciprocating tachycardia and atrial flutter-fibrillation in the Wolff-ParkinsonWhite syndrome. Circulation 56:409-416, 1977 322. Curry PVL: The hemodynamic and electrophysiological effects of paroxysmal tachycardia, in Narula OS (ed): Cardiac Arrhythmias: Electrophysiology, Diagnosis and Management. Baltimore, Williams & Wilkins, 1979, pp 364-38 I 323. Brechenmacher C: Atrio-His bundle tracts. Br Heart J 37:853-855, 1975 324. Benditt DC, Pritchett ELC, Smith WM, et al: Characteristics of atrioventricular conduction and the spectrum of arrhythmias in Lown-Ganong-Levine syndrome. Circulation 57:45&465, 1978 325. Josephson ME, Kastor JA: Supraventricular tachycardia in Lown-Ganong-Levine syndrome: Atrionodal versus intranodal reentry. Am J Cardiol40:521-527, 1977 326. Myerburg RJ, Sung RJ, Castellanos A: Ventricular
JOHN
D. FISHER
tachycardia and ventricular fibrillation in patients with short P-R intervals and narrow QRS complexes. Pace 2:568, 1979 327. Sung RJ, Gelband H, Castellanos A, et al: Clinical and electrophysiologic observations in patients with concealed accessory atrioventricular bypass tracts. Am J Cardiol40:839-847, 1977 328. Pritchett ELC, Gallagher JJ, Sealy WC, et al: Supraventricular tachycardia dependent upon accessory pathways in the absence of ventricular preexcitation. Am J Med 64:214-220, 1978 329. Ward DE, Camm AJ, Pearce RC: Incessant atrioventricular tachycardia involving an accessory pathway:Preoperative and intraoperative electrophysiologic studies and surgical correction. Am J Cardiol44:428-434, 1979 330. Orzan F, Gillette PC: Reciprocating tachycardia due to a right-sided unidirectional retrograde anomalous pathway (URAP). Pace 1:306-312,197s 331. Wu D, Denes P, Amat-Y-Leon F, et al: Clinical, electrocardiographic and electrophysiologic observations in patients with paroxysmal supraventricular tachycardia. Am J Cardiol 41:1045-1051, 1978 332. Farshidi A, Josephson ME, Horowitz LN: Electrophysiologic characteristics of concealed bypass tracts: Clinical and electrocardiographic correlates. Am J Cardiol 41:1052-1060, 1978 333. Spurrell RAJ, Krikler DM, Sowton E: Retrograde invasion of the bundle branches producing aberration of the QRS complex during SVT studied by programmed electrical stimulation. Circulation 50:487-495, 1974 334. Games JAC, Dhatt MS, Damato AN: Incidence, determinants and significance of fixed retrograde conduction in the region of the atrioventricular node. Am J Cardiol 44:1089-1098.1979 335. Spurrell RAJ, Krikler DM, Sowton E: Concealed bypasses of the atrioventricular node in patients with PCVT revealed by intracardiac electrical stimulation and verapamil. Am J Cardiol 33:590-595, 1974 336. Farre J, Ross D, Wiener I, et al: Reciprocal tachycardias using accessory pathways with long conduction times. Am J Cardiol44:1099-I 109, 1979 337. Tonkin AM: Management of arrhythmias due to accessory conduction pathways. Pace 1:482497, 1978 338. Rosen KM, Dhingra RC, Wyndham CRC: Editorial: Trading arrhythmia for atrioventricular block. Circulation 61:16-17, 1980 339. Ward DE, Camm AJ, Pearce RC:Incessant atrioventricular tachycardia involving an accessory pathway: Preoperative and intraoperative electrophysiologic studies and surgical correction. Am J Cardiol44:428-434, 1979 340. Wellens HJJ, Bar FW, Dassen WRM, et al: Effect of drugs in the Wolff-Parkinson-White syndrome. Importance of initial length of effective refractory period of the accessory pathway. Am J Cardiol46:665, 1980 341. Gallagher JJ, Sealy WC, Kasell J: Intraoperative mapping studies in the Wolff-Parkinson-White syndrome. Pace 2:523-537,1979 342. Wyndham C, Smith T, Arnsdorf M, et al: Successful surgical excision of paroxysmal atria1 tachycardia: In vivo and in vitro observations. Clin Res 27:442A, 1979 343. Klein GJ, Sealy WC, Pritchett ELC: Cryosurgical ablation of the atrioventricular node-His bundle: Long-term
ELECTROPHYSIOLOGIC
TESTING
follow-up and properties of the junctional pacemaker. Circulation 61:8-15, 1980 344. Gallagher JJ, Kasell J, Scaly WC, et al: Epicardial mapping in the Wolff-Parkinson-White syndrome. Circulation 57:854-866, 1978 345. Wyndham CR, Meeran MK, Smith T, et al: Epicardial activation of the intact human heart without conduction defect. Circulation 59:161-168, 1979 346. Sealy WC, Gallagher JJ: The surgical anatomy of Kent bundles based on electrophysiological mapping and surgical exploration. J Thorac Cardiovasc Surg 76:804-g 15, 1978 347. Gallagher JJ, Scaly WC, Kasell J, et al: Cryosurgical ablation of accessory atrioventricular connections: A method for correction of the pre-excitation syndrome. Circulation 55:471-479, 1977 348. Klein GJ, Harrison L, Ideker RD, et al: Reaction of the myocardium to cryosurgery: Electrophysiology and arrhythmogenic potential. Circulation 59:364-372, 1979 349. Fisher JD: Nonsurgical treatment of ventricular tachycardia: The value of serial provocative testing, in Narula OS (ed): Cardiac Arrhythmias: Electrophysiology, Diagnosis, and Management. Baltimore, Williams & Wilkins, 1979, pp 494-5 15 350. Waxman MB, Wald RW: Termination of ventricular tachycardia by an increase in cardiac vagal drive. Circulation 56:385-391, 1977 351. Waxman MB, Wald RW, Finley JP, et al: Valsalva termination of ventricular tachycardia. Circulation 62:843851,198O 352. Wellens HJJ, Bar FW, Lie KI: The value of the electrocardiogram in the differential diagnosis of a tachycardia with a widened QRS complex. Am J Med 64:27, 1978 353. Wit Al, Bigger JT Jr: Possible electrophysiological mechanisms for lethal arrhythmias accompanying myocardial ischemia and infarction. Circulation 51-52, (Suppl III):9661 15, 1975 354. El-Sherif N, Scherlag BJ, Lazzara R: Electrode catheter recordings during malignant ventricular arrhythmia following experimental acute myocardial ischemia. Circulation 51:1003-1014,1975 355. Kent KM, Smith ER, Redwood DR, et al: Electrical stability of acutely ischemic myocardium. Influences of heart rate and vagal stimulation. Circulation 47:291-298, 1973 356. Blatt CM, Verrier RL, Lown B: Acute blood pressure elevation and ventricular fibrillation threshold during coronary occlusion and reperfusion in the dog. Am J Cardiol 39:523-528, 1977 357. Penkoske PA, Sobel BE, Corr PB: Disparate electrophysiological alterations accompanying dysrhythmia due to coronary occlusion and reperfusion in the cat. Circulation 58:102331035, 1978 358. Murdock DK, Loeb JM, Euler DE, et al: Electrophysiology of coronary reperfusion. A mechanism for reperfusion arrhythmias. Circulation 61:175-l 82, 1980 359. Horowitz LN, Spear JF, Moore EN: Subendocardial origin of ventricular arrhythmias in 24-hour-old experimental myocardial infarction. Circulation 53:56-63, 1976 360. Spear JF, Michelson EL, Spielman SR, et al: The origin of ventricular arrhythmias 24 hours following experi-
87 mental anterior septal coronary artery occlusion. Circulation 55:844-852, 1977 361. El-Sherif N, Scherlag BJ, Lazzara R, et al: Reentrant ventricular arrhythmias in the late myocardial infarction period. I. Conduction characterictics in the infarction zone. Circulation 55:686-702, 1977 362. Myerburg RJ, Gelband H, Nilsson K, et al: Longterm electrophysiological abnormalities resulting from experimental myocardial infarction in cats. Circ Res 41:7384, 1977 363. Bailey JC, Anderson GJ, Pippenger D, et al: Reentry within the isolated canine bundle of His. Possible mechanism for reciprocal rhythm. Am J Cardiol 32:808-8 13, 1973 364. Akhtar M, Damato AN, Batsford WP, et al: Demonstration of re-entry within the His-Purkinje system in man. Circulation 50:115&l 162, 1974 365. Reddy CP, Khorasanchian A: Intraventricular reentry with narrow QRS complex. Circulation 61:641-647, 1980 366. Spureel RAJ, Sowton E, Deuchar DC: VT in 4 patients evaluated by programmed electrical stimulation of heart and treated in 2 patients by surgical division of anterior radiation of LBB. Br Heart J 35:1014-1025, 1973 367. Josephson ME, Horowitz LN, Farshidi A, et al: Sustained ventricular tachycardia: Evidence for protected localized reentry. Am J Cardiol42:416-424, 1978 368. Josephson ME, Horowitz LN, Farshidi A, et al: Recurrent sustained ventricular tachycardia. 1. Mechanisms. Circulation 57:43 1, 1978 369. Josephson ME, Horowitz LN, Farshidi A: Continuous local electrical activity. A mechanism of recurrent ventricular tachycardia. Circulation 57:659-665, 1978 370. Josephson ME, Horowitz LN, Farshidi A, et al: Recurrent sustained ventricular tachycardia. 4. Pleomorphism. Circulation. 59:459-468, 1979 371. Ross DL, Hamer AWF, Vohra JK, et al: Multiform ventricular tachycardia. Pace 3:24-37, 1980 372. Cohen SI, Deisseroth A, Hecht KS: Infra-His bundle origin of bidirectional tachycardia. Circulation 47: 12601266,1973 373. Zipes D: Electrophysiological mechanisms involved in ventricular fibrillation. Circulation 51 (Suppl III): 120, 1975 374. Spielman SR, Farshidi A, Horowitz LN, et al: Ventricular fibrillation during programmed ventricular stimulation: Incidence and clinical inplications. Am J Cardiol 42:913-918, 1978 375. Josephson ME, Spielman SR, Greenspan AM, et al: Mechanism of ventricular fibrillation in man. Observations based on electrode catheter recordings. Am J Cardiol 44:623-631, 1979 376. Engle WR, Moore EN, Spear JF, et al: The effect of multiple site pacing on ventricular fibrillation threshold. Am J Cardiol 39:274, 1977 (abstr) 377. Watson AB, Wright JS: A study of the vulnerability of the human heart to V fib during timed electrical stimulation of the T wave with pacemaker-like impulses, in Meere C (ed): Proc of the VIth World Symposium on Cardiac Pacing, Pace Symp, Montreal, 1979, pp l-6 378. Wellens HJJ, Duren DR, Lie KI: Observations on
88
mechanisms of ventricular tachycardia in man. Circulation 541237, 1976 379. Fisher JD, Cohen HL, Mehra R, et al: Cardiac pacing and pacemakers II. Serial electrophysiologic pharmacologic testing for control of recurrent tachyarrhythmias. Am Heart J 93:658-668, 1977 380. Fisher JD, Ostrow E, Mechra R, et al: Clinical correlations of ventricular vulnerability to electrophysiologic stresses, in Meere C (ed): Proc of the VIth World Symposium on Cardiac Pacing, Pace Symp, Montreal, 1979, pp l-5 38 1. Vandepol CJ, Farshidi A, Spielman SR, et al: Incidence and clinical significance of induced ventricular tachycardia. Am J Cardiol45:725-73 1, 1980 382. Horowitz LN, Josephson ME, Farshidi A, et al: Recurrent sustained ventricular tachycardia. 3. Role of the electrophysiologic study in selection of antiarrhythmic regimens. Circulation 58:986, 1978 383. Mason JW, Winkle RA: Electrode-catheter arrhythmia induction in the selection and assessment of antiarrhythmic drug therapy for recurrent ventricular tachycardia. Circulation 58:971-98.5, 1978 384. Fisher JD: Ventricular tachycardia-practical and provocative electrophysiology (editorial). Circulation 58:1000, 1978 385. Scheinman MM: Editorial: Induction of ventricular trachycardia: A promising new technique or clinical electrophysiology gone awry? Circulation 58:998-999, 1978 386. Josephson ME, Horowitz LN: Electrophysiologic approach to therapy of recurrent sustained ventricular tachycardia. Am J Cardiol43:631-642, 1979 387. Wellens HJJ: Value and limitations of programmed electrical stimulation of the heart in the study and treatment of tachycardias. Circulation 57:845, 1978 388. Lown B, Verrier RL, Blatt CM: Precordial mechanism stimulation for exposing electrical instability in the ischemic heart. Am J Cardiol42:425-428, 1978 389. Reddy CP, Gettes LS: Use of isoproterenol as an aid to electric induction of chronic recurrent ventricular tachycardia. Am J Cardiol44:705-713, 1979 390. Ruskin JN, Garan H: Chronic electrophysiologic testing in patients with recurrent sustained ventricular tachycardia. Am J Cardiol43:400, 1979 (abstr) 391. Greene HL, Reid TR, Schaeffer AH: The repetitive ventricular response in man: A predictor of sudden death. N Engl J Med 2991729. 1978 392. Schaeffer AH, Greene HL, Reid PR: Suppression of the repetitive ventricular response: an index of long-term antiarrhythmic effectiveness of aprindine for ventricular tachycardia in man. Am J Cardiol42:1007-1012, 1978 393. Fisher JD, Mehra R, Furman S: Termination of ventricular tachycardia with bursts of rapid ventricular pacing. Am J Cardiol 4 1:94-l 02, 1978 394. Fisher JD: Pacing for treatment of ventricular tachycardia, in Meere C (ed): Proceedings of the VIth World Symposium on Cardiac Pacing, Pace Symp, Montreal 1979, PP ‘-5 395. Fisher JD, Kim SC, Furman S: The role of implantable pacemakers in the control of recurrent ventricular tachycardia. Am J Cardiol (in press) 396. Horowitz LN, Horken AH, Kastor JA, et al:
JOHN
D. FISHER
Ventricular resection guided by epicardial and endocardial mapping for treatment of recurrent ventricular tachycardia. N Engl J Med 11:589-593,198O 397. Gallagher JJ, Cox JL: Editorial: Status of surgery for ventricular arrhythmias. Circulation 60:1440-1442, 1979 398. Guiraudon G, Fontaine G, Frank R: Encircling endocardial ventriculotomy: A new surgical treatment for life-threatening ventricular tachycardias resistant to medical treatment following MI. Ann Thorac Surg 26:438-444, 1978 399. Spurrell RAJ, Yates AK, Thorburn CW, et al: Surgical treatment of ventricular tachycardia following epicardial mapping studies. Br Heart J 37: 115, 1975 400. Fontaine G, Guiraudon G, et al: La Cartographie epicardique et le traitement chirurgical par simple ventriculotomie de certaines tachycardies ventriculaires rebelles par reentree. Arch Ma1 Coeur 68: 113, 1975 401. Gallagher JJ, Oldham HN, Wallace AG, et al: Ventricular aneurysm with ventricular tachycardia. Am J Cardiol 35~696, 1975 402. Gallagher JJ, Anderson RW, Kasell J, et al: Cryoablation of drug-resistant ventricular tachycardia in a patient with a variant of scleroderma. Circulation 57:190197,1977 403. Ricks WB, Winkle RA, Shumway NE, et al: Surgical management of life-threatening ventricular arrhythmias in patients with coronary artery disease. Circulation 56:3842,1977 404. Buda AJ, Stinson EB, Harrison DC: Surgery for life-threatening ventricular tachyarrhythmias. Am J Cardiol 44:1171-1177.1979 405. Thind GS, Blakemore WS, Zinsser HF: Ventricular aneurysmectomy for the treatment of recurrent ventricular tachyarrhythmia. Am J Cardiol 27:690-694, 1971 406. Basta LL, Tokeshita A, et al: Aneurysmectomy in treatment of ventricular and supraventricular tachyarrhythmias in patients with postinfarction and traumatic ventricular aneurysms. Am J Cardiol32:693, 1973 407. Wald RW, Waxman MB, Corey PN, et al: Management of intractable ventricular tachyarrhythmias after myocardial infarction. Am J Cardiol44:329-338, 1979 408. Lloyd R, Okada R, Stagg J, et al: The treatment of recurrent ventricular tachycardia with bilateral cervicothoracic sympathetic-ganglionectomy. Circulation 50:382, 1974 409. Zipes DP, Festoff B, Schaal SF, et al: Treatment of ventricular arrhythmias by permanent atrial pacemaker and cardiac sympathectomy. Ann Intern Med 68:591, 1968 410. Coyer BH, Pryor R, Kirsch WM, et al: Left stellectomy in the long QT syndrome. Chest 74:584-586, 1978 411. Wu D, Amat-Y-Leon F, Simpson RJ, et al: Electrophysiological studies with multiple drugs in patients with atriovntricular reentrant tachycardias utilizing an extranoda1 pathway. Circulation 56:727-736, 1977 412. Wu D, Wyndham CR, Denes P, et al: Chronic electrophysiologic study in patients with recurrent paroxysmal tachycardia, in Kulbertus HE (ed): A New Method for Developing Oral Antiarrhythmic Therapy. Baltimore, University Park, 1977, 294-3 11 413. Hartzler GO: Treatment of recurrent ventricular
ELECTROPHYSIOLOGIC
tachycardia by patient activated radio frequency ventricular stimulation. Mayo Clin Proc 54:75. 1979 414. Kehoe R, Bauernfeind RA, Wyndham CRC, et al: Inducible ventricular tachycardia in patients with out of hospital ventricular fibrillation. Am J Cardiol 45:444, 1980 (abstr) 415. Ruskin JN, Dimarco JP, Garan H: Electrophysiologic observations and selection of long-term antiarrhythmic therapy. New Engl J Med 303:607-613.1980 416. Mason JW, Winkle RA: Ability of induced ventricular tachycardia to predict long-term efficacy of antiarrhythmic drugs. New Engl J Med 303:1073-1077,198O 417. Horowitz LN, Josephson ME, Kastor JA: Intracardiac electrophysiologic studies as a method for the optimization of drug therapy in chronic ventricular arrhythmia. Prog in Cardiovasc Dis 23:8 l-98, 1980 418. Myerburg RJ, Conde CA, Sung RJ: Clinical, electrophysiologic and hemodynamic profile of patients resuscitated from prehospital cardiac arrest. Am J Med 68:568576,1980 419. Lie KI, Liem KL, Schuilenburg RM, et al: Early identification of patients developing late in-hospital ventricular fibrillation after discharge from the coronary care unit. Am J Cardiol41:674, I978 420. Lew HT. March HW: Control of recurrent ventricular fibrillation by transvenous pacing in the absence of heart block. Am Heart J 73~794-797, 1967 421. Haft JI: Treatment of arrhythmias by intracardiac electrical stimulation. Prog Cardiovasc Dis 16:539, 1974 422. Johnson RA, Hutter AM, De Sanctis RW, et al: Chronic overdrive pacing in the control of refractory ventricular arrhythmias. Ann Intern Med 80:380, 1974 423. Friedberg CK, Lyon LJ, Donoso E: Suppression of refractory recurrent ventricular tachycardia by transvenous rapid cardiac pacing and antiarrhythmic drugs. Am Heart J 79:44,
89
TESTING
1970
424. Moss AJ. Rivers RJ: Termination and inhibition of recurrent tachycardias by implanted pervenous pacemakers. Circulation 50:942, 1974 425. Cooper TB, Maclean WAH, Waldo AL: Overdrive pacing for supraventricular tachycardia: A Review of theoretical implications and therapeutic techniques. Pace 1:196221, 1978 426. Preston TA, Haynes RE, Gavin WA, et al: Permanent rapid atrial pacing to control supraventricular tachycardia. Pace 2:331, 1979 427. Waldo AL, Maclean WAH, Karp RB, et al: Continuous rapid atria1 pacing to control recurrent or sustained supraventricular tachycardias following open heart surgery. Circulation 54:245, 1976 428. Arbel ER, Cohen HC, Langendorf R, et al: Successful treatment of drug-resistant atrial tachycardia and intractable congestive heart failure with permanent coupled atrial pacing, Am J Cardiol41:336-340, 1978 429. Langendorf R, Pick A: Observations on the clinical use of paired electrical stimulation of the heart. Bull NY Acad Med 41:535, 1965 430. Bigger JT Jr, Jaffe CC: The effect of bretylium tosylate on the electrophysiologic properties of ventricular muscle and Purkinje fibers. Am J Cardiol 27:82-92, 1971 431. Krikler DM, Curry PVL, Buffet J: Dual-demand
pacing for reciprocating atrio-ventricular tachycardia. Br Med J 1:1114, 1976 432. Fisher JD, Furman S: Automatic termination of tachycardia by an implanted “upside down” demand pacemaker. Clin Res 26:231A, 1978 (abstr) 433. Dreifus LS, Berkovits BV, Kimibiris D, et al: Use of atria1 and bifocal cardiac pacemakers for treating resistant dysrhythmias. Eur J Cardio! 3:257, 1975 434. Sung RJ, Styperek JL, Castellanos A: Complete abolition of the reentrant SVI zone using a new modality of cardiac pacing with simultaneous atrioventricular stimulation. Am J Cardiol45:72-78, 1980 435. Akhtar M, Gilbert CJ, Al-Nouri M, et al: Electrophysiologic mechanisms for modification and abolition of atrioventricular junctional tach with simultaneous and sequential atrial and ventricular pacing. Circulation 60: 144331454, 1979 436. Spurrell RAJ, Sowton E: An implanted atrial synchronous pacemaker with a short atrioventricular delay for the prevention of paroxysmal supraventricular tachycardias. Electrocardiol 9:89, 1976 437. Critelli G, Grassi G, Chiariello M, et al: Automatic “scanning” by radiofrequency in the long-term electrical treatment of arrhythmias. Pace 2:289, 1979 438. Gurtner HP, Gertsch M, Zacouto F: Orthorhythmischer herzschrittmacher und salvenformige herzstimulation. Schweiz Med Wochenschr 105:33, 1975 439. Spurrell RAJ, Sowton E: Pacing techniques in the management of supraventricular tachycardias. J Electrocardiol 8:287, 1975 440. Escher DJW, Furman cardiac arrhythmias: Emphasis JAMA 217:2028,1970
S: Emergency treatment of on use of electrical pacing.
441. Hortzler GO: Treatment of recurrent ventricular tachycardia by patient activated radio frequency ventricular stimulation. Mayo Clin Proc 54:75, 1979 442. Goyal SL, Lichstein E, Gupta PK. et al: Refractory reentrant atrial tachycardia. Successful treatment with a permanent radio-frequency triggered atrial pacemaker. Am J Med 58:586.1975 443. Altamura G, Pistolese M, Boccadamo R: Atrial inhibited pacemaker with incorporated radiofrequency device used in the treatment of the brady-tachy syndrome, in Meere C (ed): Proc of the VI World Symposium on Cardiac Pacing, Pace Symp, Montreal. 1979, Chap 9-14 444. Kim SG, Fisher JD, Furman S, et al: Implantable ventricular burst pacemakers for termination of ventricular tachycardia, in Meere C (ed): Proc of the VI World Symposium on Cardiac Pacing, 1979, Pace Symp, Montreal. Chap 6-12 445. Neumann G, Funke H, Bakels N, et al: A new atrial demand pacemaker for the management of supraventricular tachycardias, in Meere C (ed): Proc of the VI World Symposium Cardiac Pacing, 1979, PaceSymp, Montreal, Chap 27-7 446. Furman S, Parsonnet V, Smyth N: Five-position pacemaker code (ICHD). Pace (in press) 447. Mirowski M, Mower MM, Langer A, et al: A chronically implanted system for automatic defibrillation in
90
active conscious dogs: Experimental model for treatment if sudden death from ventricular fibrillation. Circulation 58:90-94, 1978 448. Fisher JD. Ostrow E, Mehra R, et al: Clinical correlations of ventricular vulnerability to electrophysiologic stresses, in Meere C (ed): Proceedings of the VIth World Symposium on Cardiac Pacing, 1979, PaceSymp, Montreal. Chap 6-2 449. Brandenburg RO Jr, Holmes DR Jr, Hartzler Go: The electrophysiologic assessment of patients with syncope. Am J Cardiol (abstr) (in press)
JOHN
D. FISHER
450. Williams RS, Bashore TM: Proxysmal hypotension associated with sympathetic withdrawal. A new disorder of automatic vasomotor regulation. Circulation 62:901-908, 1980 45 1. Bigger JT Jr: A simple, rapid method for the diagnosis of first-degree sinoatrial block in man. Am Heart J 87:731-733, 1974 452. Engel TR, Schaal SF: Digitalis in the sick sinus syndrome: The effects of digitalis on sinoatrial automaticity and atrioventricular conduction. Circulation 48:1201-1207, 1973