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Relation of mode of induction and cycle length of ventricular tachycardia: Analysis of 104 patients
Relation of Mode of Induction and Cycle Length of Ventricular Tachycardia: Analysis of 104 Patients JOHN U. DOHERTY, MD, MICHAEL G. KIENZLE, MD, HARVEY L. WAXMAN,
MD,
ALFRED E. BUXTON, MD, FRANCIS E. MARCHLINSKI, MD, and MARK E. JOSEPHSON, MD
One hundred four consecutive patients with ventricular tachycardia (VT) were examined to correlate the cycle length with the mode of initiation of VT (single, double, and triple extrastimuli and rapid pacing). Tachycardias induced with a single extrastimulus were slower (342 f 72 ms, mean cycle length) than those induced with double (295 f 60 ms) or triple (262 f 56 ms) extrastimuli or rapid pacing (293 f 40 ms). There were no differences among the last 3 groups. In 36 patients who had endocardial catheter mapping to determine the site of origin of VT, distance from stimulation site to the site of origin was estimated and correlated with mode of initiation. There was no difference in mode of initiation when the stimulation site was close (<3
cm), intermediate (3 to 5 cm), or distant (>6 cm) from the site of origin. To address the issue of distance from stimulation site to the site of origin somewhat differently, mode of initiation was correlated with site of previous myocardial infarction in 69 patients with VT initiated from the right ventricular apex. Again, mode of initiatlon did not differ among patients with septal, inferior, lateral, or multiple myocardial infarctions. Thus, cycle length of VT inltiated with a single extrastimulus was slower than that initiated with double or triple extrastimuli or rapld pacing and the mode of initiation of VT was unrelated to site of myocardial Infarction or distance between stimulation site and site of origin of VT.
Programmed electrical stimulation has been found to be a specific and sensitive technique for the diagnosis and therapy of patients with ventricular tachycardia (VT).l-7 Although right ventricular stimulation can
induce VT in most instances, left ventricular stimulation is occasionally requirede8 It has been suggested that left ventricular stimulation be used routinely in patients in whom right ventricular stimulation fails to induce VT while the patient is receiving drugs.g Although certain general factors influencing the ability of programmed stimulation to initiate tachycardias are known, the determinants of the mode of initiation in individual patients are incompletely understood. The present study was undertaken to determine (1) the relation of the required mode of initiation and the distance between stimulation site and VT origin, (2) the effect of site of previous myocardial infarction on mode of initiation, and (3) the relation between the method of initiation and the cycle length of VT.
From the Clinical Eiectrophysiology Laboratory, Hospital of the University of Pennsylvania, Cardiovascular Section, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. Dr. Doherty received support from National Institutional Training Grant HL07346 from the National Heart, Lung, and Blood Institute, Bethesda, Maryland; he is a recipient of the Southeastern Pennsylvania Heart Association Grant-In-Aid, Philadelphia, Pennsylvania. Dr. Kienzle received support from a Fellowship Award of the Southeastern Pennsylvania Heart Association, Philadelphia, Pennsylvania. Dr. Buxton was the recipient of Research Service Award HL07201 and Dr. Josephson was the recipient of Research Career Development Award HL00361 from the National Heart, Lung, and Blood Institute, Bethesda, Maryland. This study was also supported in part by grants from the American Heart Association, Southeastern Pennsylvania Chapter, Philadelphia, Pennsylvania, and by Grant HL24278 from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. Manuscript received January 24, 1983; revised manuscript received March 16, 1983, accepted March 18, 1983. Address for reprints: John U. Doherty, MD, Cardiovascular Section, 656 Ravdin Building, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, Pennsylvania 19104.
Methods Study patients: The patient population consisted of 104 consecutive patients with inducible sustained VT during programmed ventricular stimulation. Patients in whom ventricular fibrillation or polymorphic VT causing rapid hemodynamic collapse was induced were excluded. The clinical
JULY 1983
TABLE I
Characteristics
of the Study Population (n =
104) Sex: 84 men (81%), 20 women (19%) Ages: 23 to 74 years (mean 57) Previous myocardial infarction Left ventricular aneurysm Cardiac diagnoses Coronary artery disease Valvular disease Primary electrical disease Dilated cardiomyopathy Postoperative tetralogy of Fallot
78 (75%) 59 (57%)
78 8” :
characteristics of the study population are summarized in Table I. Left ventricular endocardial catheter mapping was done in 38 patients to localize the site of origin of the VT. Electrophysiologic study: Electrophysiologic study was performed in the postabsorptive state. Ant&rhythmic agents were discontinued for at least 5 half-lives before study in all patients. Two to 6 electrode catheters were inserted percutaneously through the femoral or brachial vein and pceitioned in the heart under fluoroscopic guidance. Routinely, catheters were positioned in the high right atrium, His bundle region, coronary sinus, and right ventricular apex. Our stimulation protocol has been reported previously in detai1.2JJO Protocol: The protocol involved 4 stages. (1) Single and double ventricular premature extrastimuli were introduced during at least 2 paced cycle lengths (Sl-SI most often 600 and 400 ms) from 1 to 3 right ventricular sites. All patients were studied from the right ventricular apex. Single premature stimuli (Sz) were introduced late in diastole and moved to progressively shorter coupling intervals by 10 ms decrements until ventricular refractoriness was reached. Double premature stimuli were then introduced (Sz-S3) with the S1-S2 interval 50 to 100 ms longer than the ventricular effective refractory period and the Sp. S3 interval at twice the SI-Sz interval. The S2-S3 interval was then shortened by 10 ms decrements until S3 reached refractoriness. The Sl-S2 interval
FIGURE 1. Schema of left ventricular endocardial catheter mapping sites used in our patients in the left anterior oblique projection. Site 1 represents the left ventricular apex, sites 2 to 4 are septal, sites 5 and 8 are inferior. sites 6. 8, and 10 are basal along the mitral valve ring, and sites 7,9, 11, and 12 are on the left ventricular free wall. Sites 13 to 17 are right ventricular septal sites at the tricuspid valve, apex, mid and high septum, and outflow tract, respectively. Site 18 is the right ventricular free wall.
THE AMEIWAN JOURNAL OF CARDIOLOGY VOIUIIW 52
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was then shortened by 10 ms decrements until S3 evoked a response. This process was continued until Sp and S3 were refractory. Bursts of rapid ventricular pacing or triple premature ventricular depolarizations were then performed. Triple extrastimuli were given in all patients in whom double extrastimuli or rapid ventricular pacing failed to initiate VT. (2) Rapid ventricular pacing (I5 to 30 seconds) to a cycle length of 250 ms was delivered from 1 right ventricular site. (3) Triple premature stimuli (S&J were introduced in a fashion similar to that used previously for double premature stimuli with the Sl-Sz interval 50 to 100 ms longer than the ventricular refractory period and the S&3 interval and S&& interval 2 and 3 times the s1-S~ interval, respectively. (4) If VT was not initiated by the foregoing techniques, stimulation from the right ventricular mid-septum, outflow tract, and left ventricle was employed using a similar protocol. Stimulation was performed with a specially designed programmable stimulator (Bloom Associates, Narbeth, Pennsylvania). The stimuli were rectangular pulses 1 ms in duration delivered at twice diastolic threshold. Intracardiac electrograms were filtered at 30 to 500 Hz and simultaneously displayed with 2 to 3 surface electrocardiographic leads, usually leads 1, aVF, and V1 on a multichannel oscilloscope (Electronics for Medicine VR12 or VRI6), stored on analog tape (Honeywell 5600), or later retrieved on photographic paper and simultaneously recorded with a jet-ink recorder (Elema Mingograf) at paper speeds at 100 to 200 mm/s for real-time analysis. Endocardial catheter mapping: The catheters used for mapping included quadripolar woven dacron catheters with a 0.5 cm intraelectrode distance (USCI, Billerica, Massachusetts), and modified USC1 cournand catheters with 6 electrodes 1.5 mm apart (Wilton Webster, Los Angeles). Six right ventricular sites and I2 to I5 left ventricular sites were mapped during sinus rhythm and during VT. Each preselected site (Fig. 1) was verified by multiple plane fluoroscopy. The site of origin of the VT was defined as the site demonstrating the earliest recorded discrete or fragmented ventricular electrogram during VT using the electrode pair with a 1 cm interelectrode distance. The techniaue of endocardial catheter mapping has bean reviewed in de&l elsewhere.4.5 In those tachycardias in which the origin was localized by catheter mapping, the distance between the site of stimulation and the site of origin of the VT was determined. If the site of origin was at the site of stimulation or at an adjacent site (on the same or opposite side of the ventricular septum), it was considered close (for example, stimulation site at site 14 and site of origin at site 2). This generally corresponded to an estimated distance of <3 cm. When the site of stimulation was 23 sites removed from the site of origin, this was considered distant and corresponded to an estimated separation of >8 cm (for example, site of stimulation at site 14 with a site of origin at 10). When the site of stimulation was 2 sites away from the origin, it was termed intermediate and corresponded to a distance of 3 to 5 cm (for example, stimulation site I4 with a site of origin at 5). For this aspect of the study, stimulation was always performed from the right ventricular apex. Analysis of variance, chi-square, and unpaired student’s t test were used for statistical analysis. Results
Mode of initiation versus distance between site of origin and stimulation: In 38 patients the site of origin of VT was determined by endocardial catheter mapping. These patients were separated into 3 groups to compare the mode of initiation and the distance be-
62
INDUCTION OF VENTRICULAR TACHYCARDIA
tween the site of stimulation and the site of origin of VT when the site of stimulation was close, intermediate, or distant from the stimulation site. In all cases stimulation was performed from the right ventricular apex. Of 11 patients whose VT site of origin was close to the stimulation site, 1 required a single e&rastimulus, 6 required double extrastimuli, 2 required triple extrastimuli, and 2 required rapid pacing for initiation of their VT (Fig. 2). In patients in whom the distance was intermediate, 1 required a single extrastimulus, 5 required double extrastimuli, 1 required triple extrastimuli, and 1 required rapid pacing. Finally, in those patients in whom the site of origin was distant from the stimulation site, 3 required a single extrastimulus, 11 required double extrastimuli, 5 required triple extrastimuli, and none were initiated with rapid pacing. There was no difference in the stimulation protocol required to initiate VT when the site of origin was close, intermediate, or distant from the stimulation site (Fig. 2). Most patients required double extrastimuli for initiation in each of the groups. Mode of initiation versus site of previous myocardial infarction: In 69 patients who had VT initiated from the right ventricular apex, the mode of initiation was compared with the site of previous myocardial infarction by surface electrocardiography (Fig. 3). In patients with anteroseptal myocardial infarction, 6 were induced with a single extrastimulus, 5 were induced with double extrastimuli, 7 were induced with triple extrastimuli, and 2 were induced with rapid ventricular pacing. In patients who had an inferior wall myocardial infarction, 6 were induced by a single extrastimulus, 10 were induced by double extrastimuli, 10 were initiated by triple extrastimuli, and none were initiated with rapid pacing. In patients with lateral wall myocardial infarction, 2 were induced with a single extrastimulus, 7 were induced with double extrastimuli, 2 were induced with triple extrastimuli, and none were induced with rapid ventricular pacing. In patients with multiple myocardial infarctions, 4 were induced with a single
DISTANCE OF ORIGIN Close Single
1
1
3
c 2 -
Double
6
5
11
8
Triple
:
Rapid Pacing
1
z 8
SlTE
19
FIGURE 2. Mode of initiation is compared with distance between sites of origin and stimulation in the 38 patients who underwent complete kft ventricular mapping. Statistical analysis was done by R by C contingency tables (chi-square).
OF
Septal
PREVIOUS Inferior
INFARCTION Lateral
Multiple
Single
6
6
2
Double
5
10
7
7
Triple
7
10
2
1
Rapid Pacing
2
0
0
0
Total
20
26
11
12
5 0
2 11
Programmed electrical stimulation is a technique that has been demonstrated to be both sensitive and specific in replicating the laboratory clinical VT, and in predicting the success or failure of a drug regimen.6F7J1 Until recently, most laboratories have used single and double extrastimuli and rapid ventricular pacing as their stimulation protoco1.2J2J3 Currently, triple extrastimuli also are used. It has been stated that more vigorous stimulation may be needed if there is more intervening tissue between the stimulation site and the site of origin of the VT.14 It has even been suggested that left ventricular stimulation be used routinely in as-
Distant
oz 5
Total
Discussion
BETWEEN SITES AND STIMULATION Intermediate
2
extrastimulus, 7 were induced with double extrastimuli, 1 was induced with triple extrastimuli, and none were induced with rapid ventricular pacing. No correlation was found between the site of previous myocardial infarction and the method of initiation. Distance between site of origin and stimulation site versus cycle length of tachycardia: The cycle length of VT when the site of origin was close (mean 304 f 69 ms), intermediate (mean 356 f 63 ms), or distant (mean 325 f 57 ms) from the stimulation site were not significantly different. Mode of induction versus cycle length of VT: In the 104 patients, 126 morphoIogically distinct tachycardias were induced (for instance, contralateral bundle branch block pattern or difference in mean QRS axis 190°, Table II). The mean cycle length of VT in patients induced with a single extrastimulus was 342 f 72 ms; in those induced with double extrastimuli, 295 f 60 ms; in those induced with triple extrastimuli 282 f 56 ms, and in those induced with rapid pacing, 293 f 40 ms. The mean cycle length of VT induced with a single extrastimulus was significantly longer than that of VT induced with double or triple extrastimuli or rapid pacing. There were no significant differences among the latter 3 groups. The numbers of patients who required right ventricular outflow tract or left ventricular stimulation for initiation of VT are too small to analyze separately.
4
FIGURE 3. Mode of initiation is compared with site of previous myocardial infarction in 69 patients whose ventricular tachycardia was initiated from the right ventricular apex. Statistical analysis was done by R by C contingency tables (chi-square).
July 1983
TABLE II
Mode of lnltlation of Ventricular Tachycardia (VT) Compared With Cycle Length of the 126 Morphologically Distinct Tachycardlas in 104 Patients
Mode of Initiation of VT Single (27) Double (55) Triple (35) Rapid pacing (9)
Cycle Length of VT 342 295 282 293
f 72’ f 60 f 56 l 40
Values are means f standard deviation. Numbers in parentheses indicate number of morphologically distinct tachycardias initiated with each modality. p <0.05. l
sessing drug therapy in patients who are noninducible with right ventricular stimulations An unexpected finding in the study was the lack of correlation between the vigor of the stimulation protocol required to initiate VT and the distance between the site of stimulation and the site of origin. Early in the clinical experience with programmed stimulation, it was noted that VTs terminated with single extrastimuli had longer cycle lengths or were closer to .the site of stimulation (usually >350 ms, isilateral ventricle), or both, than those terminated with double extrastimuli (usually <350 ms, contralateral ventricle).:! It was thus reasoned that the amount of interevening tissue and, hence, the site of stimulation could influence the mode of initiation. It was also observed in patients with the preexcitation syndrome that circus movement supraventricular tachycardias utilizing a left-sided Kent bundle could occasionally not be initiated from a right-sided chamber, whereas they could be easily started by left atria1 stimulation.15 Site of stilmulation in this case appeared to relate both to the ease of creating unidirectional block and the ability of that area to recover excitability so that it could be reexcited. This observation was subsequently applied to stimulation techniques employed to initiate VT.2J2 Previous studies from our laboratory8 suggested that no clinical electro,cardiographic, hemodynamic, angiographic, or electrophysiologic characteristics were able to identify the 12 of 108 patients with VT who required left ventricular stimulation for induction of their arrhythmias. Specifically, the location of previous myocardial infarction and right or left ventricular refractoriness did not separate this group from the other patients. No explanatialn was readily apparent to explain the failure of right .ventricular stimulation in these patients. We also have correlated the distance between the site of origin and stimulation site with the cycle lengths of the VT induced. If, by chance, VT distant from the site of stimulation was slower as a group, they would be more likely to be initiated by less vigorous stimulation techniques (that is, single premature extrastimuli). This could obscure the expected findings of a more vigorous protocol required to initiate VT at a distant site. There were, however, no differences among cycle lengths of VT induced when the site of origin was close, intermediate,
THE AMERICAN JOURNAL OF CARDIOLOGY
Volume 52
63
or distant from the stimulation site. Although in all of our patients the data were related to induction from the right ventricular apex, in the small number of patients who required a different site of stimulation for induction, the distance of the stimulation site from the site of origin of the VT did not appear to influence the number of extrastimuli required to initiate the VT or its cycle length. There are too few of such patients, however, for statistical analysis. There are obvious difficulties in estimating distance from stimulation site to origin site. The largest potential source of error is the difference in heart size among patients. To overcome this difficulty, we also compared the location of previous myocardial infarction by electrocardiogram with the mode of initiation in those patients in whom VT was induced from the right ventricular apex. This site was chosen since it is reasonably reproducible from patient to patient. These results confirmed the lack of correlation between the mode of initiation and distance from stimulation to origin seen with left ventricular mapping. Patients with multiple infarctions, in whom conduction of the stimulated impulse presumably would travel through more abnormal tissue, did not require more vigorous stimulation techniques for the initiation of VT. Thus, no explanation is immediately apparent to rationalize the discordance between distance from site of stimulation to site of VT origin and mode of initiation. It may be necessary to examine 3-dimensional propagation of wavefronts and development of local block to fully develop the question. Perhaps a narrow isthmus to the site of initial block is required to initiate reentry. Our results demonstrate that VT induced with a single extrastimulus was slower than those induced with double or triple extrastimuli or by rapid pacing. There was no difference among the latter 3 groups. This suggests that in the VT initiated with a single extrastimulus, conduction may already be markedly slowed with respect to refractoriness and that additional extrastimuli are not required to prolong conduction. This slowed conduction could, of course, explain the longer cycle lengths of these tachycardias. The fact that drugs which further prolong conduction and slow VT cycle length frequently facilitate VT induction, that is, decrease the number of extrastimuli required for initiation, supports this hypothesis.16 Why VT initiated with triple extrastimuli were not more rapid than those induced with double extrastimuli is not apparent, but there are several plausible explanations. The effects on refractory periods may be maximized after 2 premature ventricular depolarizations. The added extrastimuli may, thus, either fail to shorten refractoriness or be contrabalanced by further prolongation in conduction in the other limb of the VT. The third possibility is that cycle length is not related to refractoriness. References 1. Wettens HJJ, 6chullenburg RM, Durrer D. Electrical stimulationof the heart in patients with ventricular tachycardia. Circulation 1972:46:216-226. 2. Josephson ME, Horowitz LN, Farshldi A, Kastor JA. Recurrent SuStained ventricular tachycardia. 1. Mechanisms. Circulation 1978;57:431-446. 3. Josephson ME, Herowltz LN. Electrophysiologic approach to therapy of recurrent sustained ventricular tachycardia. Am J Cardiol 1979:43:631-
64
INDUCTION OF VENTRICULAR TACHYCARDIA
642. 4. Josephson ME, tforowitz LN, Farshkli A, Spear JF, K&or JA, Moore EN. Recurrent sustained ventricular tachycardia. 2. Endocardial mapping. Circulation 1978;57:440-447. 5. JosePhson ME. Horowftx LN. Spteiman SR, Waxman HL. Greeasaan AM. Role-of catheter mapping in the preoperative evaluation of ventricular tachycardia. Am J Cardiol 1982;49:207-220. 8. VaadePoi CJ, Farshidl A, Spielman SR, Greenspan AM, Horowitz LN, Kastcu JA, Josephson ME. Sensitivity and specificity of programmed ventricular stimulation in patients with ventricular tachycardia (abstr). Am J Cardiol 1980;45:407. 7. Horowitz LN, Josephson ME, Farshldl A, Spleiman SR, Michelson EL, Greenspan AM. Recurent sustained ventricular tachycardra. 3. Role of the electrophysiol ic study in selection of antiarrhythmics. Circulation 1978;58:928-9 o! 7. 6. Robertson JF. Caln ME. Horowttz LN. Spielman SR. Greenspan AM. Waxman HL, josephsonYE. Anatomicand electrophysiologic correlatei of ventricular tachycardia requiring left ventricular stimulation.Am J Cardiol 1981;48:263-268. 9. Morady F, Heas D, Schelnman MM. Electrophysiologic drug testing in patients with malignant ventricular arrhythmias: importance of stimulation
at more than one ventricular site. Am J Cardiol 1982;50:1055-1082. 10. Jorephaen ME, Horowftx LN, Farahldl A, spielman SR, Mlchetaon EL, Greeasaan AM. Sustained ventricular tachvcardia: evidence fcr protected local&d reentry. Am J Cardiol 1976:42436-424. il. Mason JW, Wtnkie RA. Electrode-catheter arrhythmia induction in the selection and assessment of antiarrhythmic drug therapy for recurrent ventricular tachycardia. Circulation 1978;58:971-985. 12. Weilans HJJ. LX&en DR. Lte KI. Observations on mechanisms of ventricular tachycardia in man. Circulation 1978:54:237-244. 13. Denes P, Wu D, Dhlngra RA, Amat-Y-Leon F, Wyndham C, Mautner RK, Rosen KM. Electrophysiological studies in patients with chronic recurrent ventricular tachycardia. Circulation 1978;54:229-236. 14. Josephson ME, Seides SF. Recurrent ventricular tachycardia. In: Clinical Cardiac Eiectrophysiology: Techniques and Interpretations. Philadelphia: Lea 8 Febiger, 1979:247-280. 16. Wellens HJJ, Schultenber9 RM, Durter D. Electrical stimulationof the haart in Datients with Wolff-Parkinson-White svndrome, TvDe A. Circulation . 19?1;43:99-114. 16. Greenspan AM, Horowitz LN, Splelman SR, Josephson ME. Large dose procainamide therapy for ventricular tachyarrhythmia. Am J Cardiol 1980;46:453-462.
MD,
ALFRED E. BUXTON, MD, FRANCIS E. MARCHLINSKI, MD, and MARK E. JOSEPHSON, MD
One hundred four consecutive patients with ventricular tachycardia (VT) were examined to correlate the cycle length with the mode of initiation of VT (single, double, and triple extrastimuli and rapid pacing). Tachycardias induced with a single extrastimulus were slower (342 f 72 ms, mean cycle length) than those induced with double (295 f 60 ms) or triple (262 f 56 ms) extrastimuli or rapid pacing (293 f 40 ms). There were no differences among the last 3 groups. In 36 patients who had endocardial catheter mapping to determine the site of origin of VT, distance from stimulation site to the site of origin was estimated and correlated with mode of initiation. There was no difference in mode of initiation when the stimulation site was close (<3
cm), intermediate (3 to 5 cm), or distant (>6 cm) from the site of origin. To address the issue of distance from stimulation site to the site of origin somewhat differently, mode of initiation was correlated with site of previous myocardial infarction in 69 patients with VT initiated from the right ventricular apex. Again, mode of initiatlon did not differ among patients with septal, inferior, lateral, or multiple myocardial infarctions. Thus, cycle length of VT inltiated with a single extrastimulus was slower than that initiated with double or triple extrastimuli or rapld pacing and the mode of initiation of VT was unrelated to site of myocardial Infarction or distance between stimulation site and site of origin of VT.
Programmed electrical stimulation has been found to be a specific and sensitive technique for the diagnosis and therapy of patients with ventricular tachycardia (VT).l-7 Although right ventricular stimulation can
induce VT in most instances, left ventricular stimulation is occasionally requirede8 It has been suggested that left ventricular stimulation be used routinely in patients in whom right ventricular stimulation fails to induce VT while the patient is receiving drugs.g Although certain general factors influencing the ability of programmed stimulation to initiate tachycardias are known, the determinants of the mode of initiation in individual patients are incompletely understood. The present study was undertaken to determine (1) the relation of the required mode of initiation and the distance between stimulation site and VT origin, (2) the effect of site of previous myocardial infarction on mode of initiation, and (3) the relation between the method of initiation and the cycle length of VT.
From the Clinical Eiectrophysiology Laboratory, Hospital of the University of Pennsylvania, Cardiovascular Section, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. Dr. Doherty received support from National Institutional Training Grant HL07346 from the National Heart, Lung, and Blood Institute, Bethesda, Maryland; he is a recipient of the Southeastern Pennsylvania Heart Association Grant-In-Aid, Philadelphia, Pennsylvania. Dr. Kienzle received support from a Fellowship Award of the Southeastern Pennsylvania Heart Association, Philadelphia, Pennsylvania. Dr. Buxton was the recipient of Research Service Award HL07201 and Dr. Josephson was the recipient of Research Career Development Award HL00361 from the National Heart, Lung, and Blood Institute, Bethesda, Maryland. This study was also supported in part by grants from the American Heart Association, Southeastern Pennsylvania Chapter, Philadelphia, Pennsylvania, and by Grant HL24278 from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. Manuscript received January 24, 1983; revised manuscript received March 16, 1983, accepted March 18, 1983. Address for reprints: John U. Doherty, MD, Cardiovascular Section, 656 Ravdin Building, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, Pennsylvania 19104.
Methods Study patients: The patient population consisted of 104 consecutive patients with inducible sustained VT during programmed ventricular stimulation. Patients in whom ventricular fibrillation or polymorphic VT causing rapid hemodynamic collapse was induced were excluded. The clinical
JULY 1983
TABLE I
Characteristics
of the Study Population (n =
104) Sex: 84 men (81%), 20 women (19%) Ages: 23 to 74 years (mean 57) Previous myocardial infarction Left ventricular aneurysm Cardiac diagnoses Coronary artery disease Valvular disease Primary electrical disease Dilated cardiomyopathy Postoperative tetralogy of Fallot
78 (75%) 59 (57%)
78 8” :
characteristics of the study population are summarized in Table I. Left ventricular endocardial catheter mapping was done in 38 patients to localize the site of origin of the VT. Electrophysiologic study: Electrophysiologic study was performed in the postabsorptive state. Ant&rhythmic agents were discontinued for at least 5 half-lives before study in all patients. Two to 6 electrode catheters were inserted percutaneously through the femoral or brachial vein and pceitioned in the heart under fluoroscopic guidance. Routinely, catheters were positioned in the high right atrium, His bundle region, coronary sinus, and right ventricular apex. Our stimulation protocol has been reported previously in detai1.2JJO Protocol: The protocol involved 4 stages. (1) Single and double ventricular premature extrastimuli were introduced during at least 2 paced cycle lengths (Sl-SI most often 600 and 400 ms) from 1 to 3 right ventricular sites. All patients were studied from the right ventricular apex. Single premature stimuli (Sz) were introduced late in diastole and moved to progressively shorter coupling intervals by 10 ms decrements until ventricular refractoriness was reached. Double premature stimuli were then introduced (Sz-S3) with the S1-S2 interval 50 to 100 ms longer than the ventricular effective refractory period and the Sp. S3 interval at twice the SI-Sz interval. The S2-S3 interval was then shortened by 10 ms decrements until S3 reached refractoriness. The Sl-S2 interval
FIGURE 1. Schema of left ventricular endocardial catheter mapping sites used in our patients in the left anterior oblique projection. Site 1 represents the left ventricular apex, sites 2 to 4 are septal, sites 5 and 8 are inferior. sites 6. 8, and 10 are basal along the mitral valve ring, and sites 7,9, 11, and 12 are on the left ventricular free wall. Sites 13 to 17 are right ventricular septal sites at the tricuspid valve, apex, mid and high septum, and outflow tract, respectively. Site 18 is the right ventricular free wall.
THE AMEIWAN JOURNAL OF CARDIOLOGY VOIUIIW 52
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was then shortened by 10 ms decrements until S3 evoked a response. This process was continued until Sp and S3 were refractory. Bursts of rapid ventricular pacing or triple premature ventricular depolarizations were then performed. Triple extrastimuli were given in all patients in whom double extrastimuli or rapid ventricular pacing failed to initiate VT. (2) Rapid ventricular pacing (I5 to 30 seconds) to a cycle length of 250 ms was delivered from 1 right ventricular site. (3) Triple premature stimuli (S&J were introduced in a fashion similar to that used previously for double premature stimuli with the Sl-Sz interval 50 to 100 ms longer than the ventricular refractory period and the S&3 interval and S&& interval 2 and 3 times the s1-S~ interval, respectively. (4) If VT was not initiated by the foregoing techniques, stimulation from the right ventricular mid-septum, outflow tract, and left ventricle was employed using a similar protocol. Stimulation was performed with a specially designed programmable stimulator (Bloom Associates, Narbeth, Pennsylvania). The stimuli were rectangular pulses 1 ms in duration delivered at twice diastolic threshold. Intracardiac electrograms were filtered at 30 to 500 Hz and simultaneously displayed with 2 to 3 surface electrocardiographic leads, usually leads 1, aVF, and V1 on a multichannel oscilloscope (Electronics for Medicine VR12 or VRI6), stored on analog tape (Honeywell 5600), or later retrieved on photographic paper and simultaneously recorded with a jet-ink recorder (Elema Mingograf) at paper speeds at 100 to 200 mm/s for real-time analysis. Endocardial catheter mapping: The catheters used for mapping included quadripolar woven dacron catheters with a 0.5 cm intraelectrode distance (USCI, Billerica, Massachusetts), and modified USC1 cournand catheters with 6 electrodes 1.5 mm apart (Wilton Webster, Los Angeles). Six right ventricular sites and I2 to I5 left ventricular sites were mapped during sinus rhythm and during VT. Each preselected site (Fig. 1) was verified by multiple plane fluoroscopy. The site of origin of the VT was defined as the site demonstrating the earliest recorded discrete or fragmented ventricular electrogram during VT using the electrode pair with a 1 cm interelectrode distance. The techniaue of endocardial catheter mapping has bean reviewed in de&l elsewhere.4.5 In those tachycardias in which the origin was localized by catheter mapping, the distance between the site of stimulation and the site of origin of the VT was determined. If the site of origin was at the site of stimulation or at an adjacent site (on the same or opposite side of the ventricular septum), it was considered close (for example, stimulation site at site 14 and site of origin at site 2). This generally corresponded to an estimated distance of <3 cm. When the site of stimulation was 23 sites removed from the site of origin, this was considered distant and corresponded to an estimated separation of >8 cm (for example, site of stimulation at site 14 with a site of origin at 10). When the site of stimulation was 2 sites away from the origin, it was termed intermediate and corresponded to a distance of 3 to 5 cm (for example, stimulation site I4 with a site of origin at 5). For this aspect of the study, stimulation was always performed from the right ventricular apex. Analysis of variance, chi-square, and unpaired student’s t test were used for statistical analysis. Results
Mode of initiation versus distance between site of origin and stimulation: In 38 patients the site of origin of VT was determined by endocardial catheter mapping. These patients were separated into 3 groups to compare the mode of initiation and the distance be-
62
INDUCTION OF VENTRICULAR TACHYCARDIA
tween the site of stimulation and the site of origin of VT when the site of stimulation was close, intermediate, or distant from the stimulation site. In all cases stimulation was performed from the right ventricular apex. Of 11 patients whose VT site of origin was close to the stimulation site, 1 required a single e&rastimulus, 6 required double extrastimuli, 2 required triple extrastimuli, and 2 required rapid pacing for initiation of their VT (Fig. 2). In patients in whom the distance was intermediate, 1 required a single extrastimulus, 5 required double extrastimuli, 1 required triple extrastimuli, and 1 required rapid pacing. Finally, in those patients in whom the site of origin was distant from the stimulation site, 3 required a single extrastimulus, 11 required double extrastimuli, 5 required triple extrastimuli, and none were initiated with rapid pacing. There was no difference in the stimulation protocol required to initiate VT when the site of origin was close, intermediate, or distant from the stimulation site (Fig. 2). Most patients required double extrastimuli for initiation in each of the groups. Mode of initiation versus site of previous myocardial infarction: In 69 patients who had VT initiated from the right ventricular apex, the mode of initiation was compared with the site of previous myocardial infarction by surface electrocardiography (Fig. 3). In patients with anteroseptal myocardial infarction, 6 were induced with a single extrastimulus, 5 were induced with double extrastimuli, 7 were induced with triple extrastimuli, and 2 were induced with rapid ventricular pacing. In patients who had an inferior wall myocardial infarction, 6 were induced by a single extrastimulus, 10 were induced by double extrastimuli, 10 were initiated by triple extrastimuli, and none were initiated with rapid pacing. In patients with lateral wall myocardial infarction, 2 were induced with a single extrastimulus, 7 were induced with double extrastimuli, 2 were induced with triple extrastimuli, and none were induced with rapid ventricular pacing. In patients with multiple myocardial infarctions, 4 were induced with a single
DISTANCE OF ORIGIN Close Single
1
1
3
c 2 -
Double
6
5
11
8
Triple
:
Rapid Pacing
1
z 8
SlTE
19
FIGURE 2. Mode of initiation is compared with distance between sites of origin and stimulation in the 38 patients who underwent complete kft ventricular mapping. Statistical analysis was done by R by C contingency tables (chi-square).
OF
Septal
PREVIOUS Inferior
INFARCTION Lateral
Multiple
Single
6
6
2
Double
5
10
7
7
Triple
7
10
2
1
Rapid Pacing
2
0
0
0
Total
20
26
11
12
5 0
2 11
Programmed electrical stimulation is a technique that has been demonstrated to be both sensitive and specific in replicating the laboratory clinical VT, and in predicting the success or failure of a drug regimen.6F7J1 Until recently, most laboratories have used single and double extrastimuli and rapid ventricular pacing as their stimulation protoco1.2J2J3 Currently, triple extrastimuli also are used. It has been stated that more vigorous stimulation may be needed if there is more intervening tissue between the stimulation site and the site of origin of the VT.14 It has even been suggested that left ventricular stimulation be used routinely in as-
Distant
oz 5
Total
Discussion
BETWEEN SITES AND STIMULATION Intermediate
2
extrastimulus, 7 were induced with double extrastimuli, 1 was induced with triple extrastimuli, and none were induced with rapid ventricular pacing. No correlation was found between the site of previous myocardial infarction and the method of initiation. Distance between site of origin and stimulation site versus cycle length of tachycardia: The cycle length of VT when the site of origin was close (mean 304 f 69 ms), intermediate (mean 356 f 63 ms), or distant (mean 325 f 57 ms) from the stimulation site were not significantly different. Mode of induction versus cycle length of VT: In the 104 patients, 126 morphoIogically distinct tachycardias were induced (for instance, contralateral bundle branch block pattern or difference in mean QRS axis 190°, Table II). The mean cycle length of VT in patients induced with a single extrastimulus was 342 f 72 ms; in those induced with double extrastimuli, 295 f 60 ms; in those induced with triple extrastimuli 282 f 56 ms, and in those induced with rapid pacing, 293 f 40 ms. The mean cycle length of VT induced with a single extrastimulus was significantly longer than that of VT induced with double or triple extrastimuli or rapid pacing. There were no significant differences among the latter 3 groups. The numbers of patients who required right ventricular outflow tract or left ventricular stimulation for initiation of VT are too small to analyze separately.
4
FIGURE 3. Mode of initiation is compared with site of previous myocardial infarction in 69 patients whose ventricular tachycardia was initiated from the right ventricular apex. Statistical analysis was done by R by C contingency tables (chi-square).
July 1983
TABLE II
Mode of lnltlation of Ventricular Tachycardia (VT) Compared With Cycle Length of the 126 Morphologically Distinct Tachycardlas in 104 Patients
Mode of Initiation of VT Single (27) Double (55) Triple (35) Rapid pacing (9)
Cycle Length of VT 342 295 282 293
f 72’ f 60 f 56 l 40
Values are means f standard deviation. Numbers in parentheses indicate number of morphologically distinct tachycardias initiated with each modality. p <0.05. l
sessing drug therapy in patients who are noninducible with right ventricular stimulations An unexpected finding in the study was the lack of correlation between the vigor of the stimulation protocol required to initiate VT and the distance between the site of stimulation and the site of origin. Early in the clinical experience with programmed stimulation, it was noted that VTs terminated with single extrastimuli had longer cycle lengths or were closer to .the site of stimulation (usually >350 ms, isilateral ventricle), or both, than those terminated with double extrastimuli (usually <350 ms, contralateral ventricle).:! It was thus reasoned that the amount of interevening tissue and, hence, the site of stimulation could influence the mode of initiation. It was also observed in patients with the preexcitation syndrome that circus movement supraventricular tachycardias utilizing a left-sided Kent bundle could occasionally not be initiated from a right-sided chamber, whereas they could be easily started by left atria1 stimulation.15 Site of stilmulation in this case appeared to relate both to the ease of creating unidirectional block and the ability of that area to recover excitability so that it could be reexcited. This observation was subsequently applied to stimulation techniques employed to initiate VT.2J2 Previous studies from our laboratory8 suggested that no clinical electro,cardiographic, hemodynamic, angiographic, or electrophysiologic characteristics were able to identify the 12 of 108 patients with VT who required left ventricular stimulation for induction of their arrhythmias. Specifically, the location of previous myocardial infarction and right or left ventricular refractoriness did not separate this group from the other patients. No explanatialn was readily apparent to explain the failure of right .ventricular stimulation in these patients. We also have correlated the distance between the site of origin and stimulation site with the cycle lengths of the VT induced. If, by chance, VT distant from the site of stimulation was slower as a group, they would be more likely to be initiated by less vigorous stimulation techniques (that is, single premature extrastimuli). This could obscure the expected findings of a more vigorous protocol required to initiate VT at a distant site. There were, however, no differences among cycle lengths of VT induced when the site of origin was close, intermediate,
THE AMERICAN JOURNAL OF CARDIOLOGY
Volume 52
63
or distant from the stimulation site. Although in all of our patients the data were related to induction from the right ventricular apex, in the small number of patients who required a different site of stimulation for induction, the distance of the stimulation site from the site of origin of the VT did not appear to influence the number of extrastimuli required to initiate the VT or its cycle length. There are too few of such patients, however, for statistical analysis. There are obvious difficulties in estimating distance from stimulation site to origin site. The largest potential source of error is the difference in heart size among patients. To overcome this difficulty, we also compared the location of previous myocardial infarction by electrocardiogram with the mode of initiation in those patients in whom VT was induced from the right ventricular apex. This site was chosen since it is reasonably reproducible from patient to patient. These results confirmed the lack of correlation between the mode of initiation and distance from stimulation to origin seen with left ventricular mapping. Patients with multiple infarctions, in whom conduction of the stimulated impulse presumably would travel through more abnormal tissue, did not require more vigorous stimulation techniques for the initiation of VT. Thus, no explanation is immediately apparent to rationalize the discordance between distance from site of stimulation to site of VT origin and mode of initiation. It may be necessary to examine 3-dimensional propagation of wavefronts and development of local block to fully develop the question. Perhaps a narrow isthmus to the site of initial block is required to initiate reentry. Our results demonstrate that VT induced with a single extrastimulus was slower than those induced with double or triple extrastimuli or by rapid pacing. There was no difference among the latter 3 groups. This suggests that in the VT initiated with a single extrastimulus, conduction may already be markedly slowed with respect to refractoriness and that additional extrastimuli are not required to prolong conduction. This slowed conduction could, of course, explain the longer cycle lengths of these tachycardias. The fact that drugs which further prolong conduction and slow VT cycle length frequently facilitate VT induction, that is, decrease the number of extrastimuli required for initiation, supports this hypothesis.16 Why VT initiated with triple extrastimuli were not more rapid than those induced with double extrastimuli is not apparent, but there are several plausible explanations. The effects on refractory periods may be maximized after 2 premature ventricular depolarizations. The added extrastimuli may, thus, either fail to shorten refractoriness or be contrabalanced by further prolongation in conduction in the other limb of the VT. The third possibility is that cycle length is not related to refractoriness. References 1. Wettens HJJ, 6chullenburg RM, Durrer D. Electrical stimulationof the heart in patients with ventricular tachycardia. Circulation 1972:46:216-226. 2. Josephson ME, Horowitz LN, Farshldi A, Kastor JA. Recurrent SuStained ventricular tachycardia. 1. Mechanisms. Circulation 1978;57:431-446. 3. Josephson ME, Herowltz LN. Electrophysiologic approach to therapy of recurrent sustained ventricular tachycardia. Am J Cardiol 1979:43:631-
64
INDUCTION OF VENTRICULAR TACHYCARDIA
642. 4. Josephson ME, tforowitz LN, Farshkli A, Spear JF, K&or JA, Moore EN. Recurrent sustained ventricular tachycardia. 2. Endocardial mapping. Circulation 1978;57:440-447. 5. JosePhson ME. Horowftx LN. Spteiman SR, Waxman HL. Greeasaan AM. Role-of catheter mapping in the preoperative evaluation of ventricular tachycardia. Am J Cardiol 1982;49:207-220. 8. VaadePoi CJ, Farshidl A, Spielman SR, Greenspan AM, Horowitz LN, Kastcu JA, Josephson ME. Sensitivity and specificity of programmed ventricular stimulation in patients with ventricular tachycardia (abstr). Am J Cardiol 1980;45:407. 7. Horowitz LN, Josephson ME, Farshldl A, Spleiman SR, Michelson EL, Greenspan AM. Recurent sustained ventricular tachycardra. 3. Role of the electrophysiol ic study in selection of antiarrhythmics. Circulation 1978;58:928-9 o! 7. 6. Robertson JF. Caln ME. Horowttz LN. Spielman SR. Greenspan AM. Waxman HL, josephsonYE. Anatomicand electrophysiologic correlatei of ventricular tachycardia requiring left ventricular stimulation.Am J Cardiol 1981;48:263-268. 9. Morady F, Heas D, Schelnman MM. Electrophysiologic drug testing in patients with malignant ventricular arrhythmias: importance of stimulation
at more than one ventricular site. Am J Cardiol 1982;50:1055-1082. 10. Jorephaen ME, Horowftx LN, Farahldl A, spielman SR, Mlchetaon EL, Greeasaan AM. Sustained ventricular tachvcardia: evidence fcr protected local&d reentry. Am J Cardiol 1976:42436-424. il. Mason JW, Wtnkie RA. Electrode-catheter arrhythmia induction in the selection and assessment of antiarrhythmic drug therapy for recurrent ventricular tachycardia. Circulation 1978;58:971-985. 12. Weilans HJJ. LX&en DR. Lte KI. Observations on mechanisms of ventricular tachycardia in man. Circulation 1978:54:237-244. 13. Denes P, Wu D, Dhlngra RA, Amat-Y-Leon F, Wyndham C, Mautner RK, Rosen KM. Electrophysiological studies in patients with chronic recurrent ventricular tachycardia. Circulation 1978;54:229-236. 14. Josephson ME, Seides SF. Recurrent ventricular tachycardia. In: Clinical Cardiac Eiectrophysiology: Techniques and Interpretations. Philadelphia: Lea 8 Febiger, 1979:247-280. 16. Wellens HJJ, Schultenber9 RM, Durter D. Electrical stimulationof the haart in Datients with Wolff-Parkinson-White svndrome, TvDe A. Circulation . 19?1;43:99-114. 16. Greenspan AM, Horowitz LN, Splelman SR, Josephson ME. Large dose procainamide therapy for ventricular tachyarrhythmia. Am J Cardiol 1980;46:453-462.