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Determinants of prognosis in idiopathic dilated cardiomyopathy as determined by programmed electrical stimulation
CARDIOMYOPATHY
Determinants of Prognosis in Idiopathic Dilated Cardiomyopathy as Determined by Programmed Electrical Stimulation THOMAS MEINERTZ, MD, NORBERT TREESE, MD, WOLFGANG ANNETTE GEIBEL, MD, THOMAS
HOFMANN,
KASPER, MD,
MD, MANFRED ZEHENDER, MD,
DORIS BOHN, MD, TIBERIUS POP, MD, and HANJOERG JUST, MD
The incidence and prognostic significance of electrically induced ventricular arrhythmias were prospectively assessed in 42 patients with idiopathic dilated cardiomyopathy. All patients underwent 24-hour, long-term electrocardiographic (Holter) monitoring and 30 were analyzed by a signal-averag ing vectorcardiographic procedure at entry into the study. Their response to programmed electrical stimulation during basic right ventricular pacing was tnvestigated using 1 and 2 ventricular extrastimuli. A monomorphic tachycardia was not induced in any atient. In 36 patients (66%) polymorphic ventricular arrhythmias were initiated. Three or more induced consecutive ventricular premature complexes occurred in 9 patients (21%), nonsustained polymorphic ventricular tachycardia in 2 (4.6%) and ventricular fibrillation in 1 patient (2.4%). There was no association between electrically induced poly-
morphic ventricular arrhythmias and the degree of impairment of left ventricular function. Furthermore, the incidence of induced ventricular arrhythmias was not related to the Lown grade or to the total number of ventricular premature complexes during Holter monitoring. A late potential was detected by the averaged vectorcardiogram in only 1 of the 30 patients. During follow-up (mean 16 f 7 months) 7 patients died, 5 from chronic congestive heart failure and 2 from sudden cardiac death. No patient .had an electrically induced arrhythmia of 3 or more ventricular premature complexes. Thus, in most patients with idiopathic dilated cardiomyopathy, programmed electrical stimulation of the right ventricle with up to 2 extrastimuli fails to reproduce an electrophysiologic correlate to the frequent ventricular arrhythmias. (Am J Cardiol 1
Recently we reported on the prognostic impact of spontaneous ventricular arrhythmias and hemodynamic variables in 74 patients with idiopathic dilated cardiomyopathy (1DQ.l To identify patients who are at risk for sudden cardiac death, specific criteria for the interpretation of the 24-hour electrocardiogram (EC@) or other techniques capable of detecting ventricular electrical instability are required. Signal averaging of tbe high-frequency components of the QRS complexes
appears to be a promising noninvasive technique for detecting patients at risk of sustained ventricular tachycardia. 2-5 The incidence and clinical significance of these signals in patients with IDC are unknown. Another technique found to be useful to study patients with coronary artery disease and IDC at risk for sudden cardiac death is programmed electrical stimulation of the heart.6-g Whether these techniques can be either useful in a greater population of patients with IDC to evaluate ventricular electrical instability and their degree of susceptibility to die suddenly is not known. This study determines in an unselected group of patients with IDC whether programmed electrical stimulation of the heart, either alone or combined with noninvasive techniques such as signal averaging and Holter monitoring, can be useful to assess the degree of ventricular electrical instability and risk of sudden cardiac death.
From the lnnere Medizin lllV Universitaet Freiburg, Freiburg, and II Medizinische Klinik und Poliklinik, Universitaet Mainz, Mainz, Federal Republic of Germany. Manuscript received January 8, 1985; revised manuscript received March 27, 1985, accepted March 29, 1985. Address for reprints: Thomas Meinertz, MD, lnnere Medizin Ill der Universitaet Freiburg, Hugstetterstr. 55, D-7800 Freiburg, Federal Republic of Germany. 337
338
PROGNOSIS IN IDIOPATHIC DILATED CARDIOMYOPATHY
Methods Forty-two consecutive patients diagnosed as having IDC according to the criteria proposed by Goodwin and Oakley were studied after they gave informed, written consent. The patients represent a subgroup of 74 patients with IDC previously investigate@ and were studied by programmed electrical stimulation only by a later time of admission to our hospital. Thirty-eight patients were men and 4 were women, mean age 45 f 9 years (range 10 to 64). At entry of the study all underwent right- and left-sided cardiac catheterization, including measurements of right and left ventricular pressures, cardiac index, left ventriculography using simultaneous biplane views, and coronary cineangiography. Patients also underwent M-mode and 2-dimensional echocardiography (Varian 3400, transducer 2.25 MHz, 2 cm in diameter, unfocused) and radionuclide angiography (first-pass technique). The clinical, hemodynamic and angiographic criteria for the study patients are as described previous1y.l Electrophysiologic study: Patients were in the postabsorptive and nonsedated state. All antiarrhythmic drugs had been withheld for at least 4 half-lives. A quadripolar catheter (electrode distance 1.0 cm) was introduced into the femoral vein and placed in the right ventricular apex. An intraventricular electrogram was recorded from the proximal 2 poles of the catheter, together with the standard electrocardiographic leads I, aVF and VI. The distal 2 poles of the quadripolar catheter were used for pacing. All signals were recorded simultaneously on a 8-channel jet recorder (Mingograph, Siemens Elema). Programmed electrical stimulation was performed with a conduction system analyzer (Medtronic, 5325). The stimuli were 1.8 ms in duration and twice diastolic threshold (less than 3 mA). The stimulation protocol was the same in all patients and included the introduction of single and double ventricular extrastimuli at a basic drive of 500,600 and 430 ms. After every 8 beats 1 premature stimulus (SZ)was introduced late in diastole and then progressively shortened by lo-ms steps until ventricular refractoriness was reached. Thereafter, S2 was set 20 ms outside the effective refractory period. A second extrastimulus (S3) was added 300 ms after Sz and scanned at lo-ms intervals up to the refractory period of the right ventricle. The endpoints of testing were the initiation of 5 or more nonpaced consecutive ventricular premature complexes (VPCs) or each extrastimulus brought to its refractory period.lOJl Definitions: For the purpose of this study the following definitions were used? Electrically induced ventricular premature complexes-VPCs 0 to 2: up to 2 nonpaced consecutive VPCs; VPCs 3 to 5: 3 to 5 nonpaced consecutive VPCS. HV intervals were not measured and no effort was made to distinguish between intraventricular or bundle branch reentry. Nonsustained
polymorphic
ventricular
tachycardia
(VT)-6 or more VPCs with a rate more than 100 beats/min and a well defined QRS complex in the surface leads with continuous changes in axis and morphology, lasting less than 30 seconds and with no intervention required for termination. Ventricular fibrillation (VF): ventricular arrhythmias with disorganized electrical activity in the surface electrocardiogram and no clear identifiable QRS complexes. The definition of sustained monomorphic VT and sustainment of VT are as reported previously.12 Signal averaging: Determination of late potentials from the body surface with high-gain amplification and the signal technique was performed using the Marquette system. The computer uses a set of 3 bipolar, 3 augmented electrodes to
internally construct 6 leads which represent vectors at 30’ increments in a plane defined by the 3 electrodes.A horizontal plane was formed by VI, Vd and Vs chest leads and the frontal plane was formed by the right and left shoulders and the left inguinal region. In each patient, 256 to 512 consecutivecardiac cycles were summed. By means of a pattern matching technique only cycles that corresponded to more than 95% “fit” were accepted. Thus, noisy, aberrant cycles and ventricular arrhythmias were not averaged. The sampling rate was 2,000 samples/s and the resolution was thus less than 0.5 ms. The trigger point is based on the earliest onset of QRS activity. The total system gain was 1 X 105. Output filtration consisted of a Butterworth low-pass filter for the 300 Hz fixed upper frequency cutoff. High-pass filtration was achieved by 0 phase, P-pole digital filters (Butterworth) at 50,100 and 200 Hz (18 db/octave). The following filter settings were used: 50 to 300 Hz, 100 to 300 Hz and 200 to 300 Hz. The resulting averages were recorded on a 3-channel direct-writing recorder at the basic sensitivities of 4000 mm/mV (high resolution) and 200 mm/mV (low resolution) at a paper speed of 400 mm/s. Late potentials were identified visually in the high-gain averaged recordings as low-amplitude activity appearing at least 10 ms after the end of the QRS complex in the low-resolution ECG. Furthermore, these potentials had to be present in at least 5 of the 12 high-resolution electrocardiographic tracings. Using these criteria for the definition of late potentials, a good correlation between the findings with different averaging techniques has been found.13 Holter monitoring: All patients underwent 24-hour Holter monitoring at entrance into the study. Perpendicular leads approximating leads V2 and Vs were recorded simultaneously. The tapes were analyzed semiautomatically using the Siemens Meditape arrhythmia computer. Then, the recordings were scanned again visually at 60 times and 30 times real speed for detecting complex ventricular arrhythmias (ventricular pairs; VT defined as more than consecutiveVPCs at rates of more than lOO/min). Each arrhythmia event detected was written out in real time on standard electrocardiographic paper. All documented arrhythmias were interpreted by 2 independent cardiologists. The sensitivity and specificity of the Holter analysis has been tested by visual real time analysis and found to be more than 90% for VPCs, ventricular pairs and VT. Statistical methods: All calculations were performed on an Honeywell 66-80 computer using the BMDP program. Most data are expressed as mean f standard deviation; only the arrhythmic variables (VPCs/24 hours, ventricular pairs/24 hours, VT/24 hours) are expressedas median values with the 25th and 75th quantiles because of their asymmetric distribution. The relation between the results of Holter monitoring and of programmed electrical stimulation was analyzed by chi-square analysis and Fisher’s exact test. The relation between repetitive ventricular responses and left ventricular function was analyzed by l-way analysis of variance.
Results Clinical, electrocardiographic and hemodynamic findings: The clinical and electrocardiographicfindings
at entry into the study are summarized in Table I. Programmed ventricular stimulation: The results of programmed ventricular stimulation are shown in Figure 1. In all but 6 patients (86%), a ventricular arrhythmia was induced by programmed electrical stimulation. However, 6 or more consecutive VPCs were induced in only 3 (7%) patients. One patient had VF that required defibrillation and 2 patients had a nonsustained polymorphic VT, which lasted for 8 VPCs in 1 patient and 43 VPCs in the other (mean cycle length
August i, 1985
TABLE I
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Characterization of the 42 Patients by Clinical and Electrocardiographic Criteria
NYHA classification 6 Iii IV Surface ECG LBBB RBBB LAH AF
n
%
c
10 is 43 19
:A 8 13 0 11 8
3.39
NSPVT VFRVR3
2: 19
360 and 195 ms, respectively). A monomorphic type of VT was observed in no patient studied. There was no association between the results of ventricular stimulation and the degree of impairment of left ventricular function (Table II). During programmed electrical stimulation, 43% of the patients received cardioactive medication (digitalis and nitrates). The results of programmed electrical stimulation were not related to this therapy. Holter monitoring: Eighty-eight percent of the patients had ventricular arrhythmias. Nineteen percent had Lown grade III and 19% Lown grade IVA arrhythmias. Thirty-six percent of the patients had VT episodes (Lown IVB), which were sustained in 2 patients (lasting more than 30 seconds). In these 2 patients the left ventricular ejection fraction was 38% and 46%. The ventricular rate during VT ranged from 108 to 223 VPCs/min (mean 153 f 28). Seven of 23 patients with Lown grade IVAIIVB arrhythmias had more than 20 episodes of VT or ventricular pairs during 24 hours. Signal averaging: A late potential was detected by the averaging technique from the body surface in only 1 of the 30 patients studied. The duration of this late potential was less than 20 ms.
Correlation between programmed electrical stimulation and Holter monitoring: The relation between ventricular arrhythmias registrated by the Holter monitoring and the results of programmed electrical stimulation is listed in Table III. No correlation was found between the number of induced VPCs and the grade of ventricular arrhythmia according to the
elation Between the Results Ventricular Function o-2 VPCS Induced
LVEF (%) LVEDVI (ml/m*) LVEDP (mm Hg) Cl (liters/min/m*)
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AF = atrial fibrillation; ECG = electrocardiogram; LAH = left anterior hemiblock; LBBB = left bundle branch block; NYHA = New York Heart Association; RBBB = right bundle branch block.
TABLE II
OF CARDIOLOGY
37f 17 217 f 63 12f8 3.3 f 0.9
FIGURE 1. Results of programmed electrical stimulation in 42 patients with idiopathic dilated cardiomyopathy. RVR O-2 and 3-5 = repetitive ventricular responses of 0 to 2 or 3 to 5 consecutive ventricular complexes; NSPVT = nonsustained polymorphic ventricular tachycardia; VF = ventricular fibrillation.
Lown classification. The incidence of responses lasting 3 to 5 VPCs and VT/VF was similar in patients with Lown grade 0, I and II, III and IVA, and IVB arrhythmias and independent of the number of VPCs observed during Holter monitoring. In none of the 15 patients with clinically documented VT, i.e. Lown grade IVB, was a sustained monomorphic VT induced, neither a polymorphic sequence of more than 6 complexes or VF. Furthermore, the incidence of induced VPCs lasting 3 to 5 complexes as well as nonsustained polymorphic VT and VF was not related to the number of VPCs or to the Lown grade during Holter monitoring. Outcome: The mean follow-up for patients was 16 f 7 months (range 2 to 24) and at least 12 months for all subjects who survived. Five patients died of chronic heart failure and 2 died suddenly from cardiac causes (unexpected death within 1 hour of onset of symptoms). The hemodynamic and arrhythmic variables found in these patients are listed in Table IV. In none was a monomorphic VT induced, nor was a nonsustained polymorphic VT or VF initiated, Furthermore, no abnormal potentials were found at averaged vectorcardiography in this group of patients. All patients who died suddenly and 2 of the patients who died from chronic heart failure had Lown grade IVB arrhythmias. During follow-up no patient received antiarrhythmic or /3-receptor blocking agents. The medication with digitalis,
f programmer 3-5 VPCS Induced 51 173 11 3.7
f6 f 60 f9 f 0.6
Ventricular
Stimulatio
NSPVT, VF Induced 47f 17 160 f 30 6f3 2.8 f 0.7
p Value NS NS NS NS
Comparison between the mean values of the 3 subgroups (PVCs O-2 or 3-5, NSPVT and VF) was performed by using a l-way analysis of variance. Cl = cardiac index; LVEDP = left ventricular end-diastolic pressure; LVEDVI = left ventricular enddiastolic volume index; LVEF = left ventricular ejection fraction; NS = not significant; NSPVT = nonsustained polymorphic ventricular tachycardia; VF = ventricular fibrillation; VPCs O-2 or 3-5 = repetitive ventricular response of 0 to 2 or 3 to 5 consecutive ventricular complexes.
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PROGNOSIS
TABLE Ill
DILATED
CARDIOMYOPATHY
Relation Between Repetitive Ventricular Response and Arrhythmic Events During 24-Hour Holter Monitoring
Holter/PES induced Lown O-II Lown IWIVA Lown IVB
IN IDIOPATHIC
TABLE IV
Pt
o-2 VPCS Induced
3-5 VPCS Induced
NSPVT, VF
8
1
2
;
i
if
The analysis was performed by chi-square analysis and Fisher’s exact test (x2 = 3.6, not significant). Arrhythmic events were classified according to the Lown classification. NSPVT = nonsustained polymorphic ventricular tachycardia; PES = programmed electrical stimulation; VF = ventricular fibrillation; VPCs O-2 and 3-5 = repetitive ventricular response of 0 to 2 or 3 to 5 consecutive ventricular complexes.
diuretics and nitrates was modified according to the clinical situation. All patients who died had a severe impairment of left ventricular function, with a left ventricular ejection fraction below 30%, a correlation which was found to be significant in the patients with 1DC.l
Discussion This prospective study was directed to answer 3 questions: What is the incidence of ventricular arrhythmias induced by ventricular stimulation in patients with IDC? What is the clinical and prognostic significance of these arrhythmias? What is the relationship between the arrhythmias induced by ventricular extrastimuli and the results of signal averaging and Holter monitoring? Programmed electrical stimulation can reproducibly replicate VT in patients with coronary artery disease suffering clinically from sustained VT. Among patients considered to be at high risk of sudden cardiac death, programmed electrical stimulation has been used,14-l7 especially in patients who survive out-of-hospital cardiac arrest or who have sustained forms of VT.6Js In patients with IDC considered to be at high risk for life-threatening arrhythmias and sudden cardiac death, the experience with programmed electrical stimulation is limited.gJg-22 The main purpose of our study was therefore to apply ventricular stimulation to a larger group of unselected patients with IDC in order to define the incidence and potential prognostic impact of inducible ventricular arrhythmias in this particular population and to compare programmed electrical stimulation with other noninvasive techniques such as Holter monitoring and signal averaging. Incidence and type of repetitive responses induced: Our results show that an electrically induced ventricular arrhythmia of 6 or more PVCs was observed in only 7.1% of patients with IDC. None of these arrhythmias can be considered a “specific” response to uncover an electrophysiologic correlate to the high incidence of ventricular arrhythmias in these patients. The value of VF induced with 1 and 2 extrastimuli is not known in patients with coronary artery disease,12J3,23 and appears more likely to be an unspecific response also in patients with IDC. These data are similar with those reported by Wellens et a120and Nacarelli et a121and suggest a very low rate
1 : : ;
Characterization Follow-Up
Cause of Death SCD SCD CHF CHF CHF CHF CHF
LVEF (% ) 2 :: 22 ::
of Patients Who Died During Lown Class
Induced VPCS
Late Potential
IVB IVB IVB Ill IVA Ill IVB
1
-
0’ 2 2
q
i
-
CHF = chronic heart failure; LVEF = left ventricular ejection fraction; SCD = sudden cardiac death; VPCs = ventricular premature com-
plexes.
of inducibility of sustained episodes of VT in patients who present with IDC. Wellens et a120reported 3 patients with IDC of 50 patients studied because of sustained VT, who, in contrast to patients with coronary artery disease, did not have VT inducible by programmed electrical stimulation. Nacarelli et a121induced a sustained VT in 6 of 37 patients with different types of cardiomyopathy; 30 of these patients had IDC and 25 had documented VT; further detailed informations on VT were not reported. In a more recent study on a selected group of patients with IDC with a mean ejection fraction of 30% and a history of sustained uniform VT, Poll et al9 found an inducibility rate of 100% for sustained monomorphic VT using an extensive left and right ventricular stimulation protocol.g However, 10 of 11 patients required a stimulation mode using 3 extrastimuli, a stimulation site different from the right ventricular apex, left ventricular pacing or the administration of antiarrhythmic agents. The incidence of induced VPCs observed in our study (79% of patients), and the induction of nonsustained polymorphic VT (5%) are a well known phenomenon during programmed electrical stimulation, and have no relation to clinical arrhythmia even in patients with coronary artery disease.12*23924 Our results suggest that these arrhythmias are nonspecific also in patients with IDC. Stimulation protocol: The mode and extent of ventricular stimulation should be considered when analyzing the incidence and significance of induced VPCs. In this study 1 and 2 extrastimuli were introduced during ventricular drive at 3 basic cycle lengths in the right ventricle. This is a simple, however, for the initiation of sustained VT specific protocol, because it has been demonstrated12 that stimulation with more than 2 extrastimuli may result in progressively more nonspecific responses and some “false-positive” results, as well as in an increase in the number of countershocks required to terminate induced arrhythmias. Using such a nonvigorous stimulation protocol the 2 patients with clinically asymptomatic VT during Holter monitoring had no inducible sustained VT. Both of them remained asymptomatic during follow-up. A further aspect we have to consider is the endpoint used during programmed electrical stimulation. In this study we chose the induction of 5 or more nonpaced This will be a matter of VPCs as an endpoint. 3~11p24
August 1, 1965
discussionbecauseof the high-risk profile of this group, but otherwise such patients studied had been asymptomatic with regard to ventricular arrhythmias. However,during this study in only 3 of 42 patients was more ihan 5 VPCs an en,&347 ” I +I, +“V %P”?Fdo ““.&A -Ll-l” tllo Cer- qtimlllqt~rr~ -i --_-_.--.*
protocol (1 patient with VI? and 2 patients with non sustained polymorphic VT), all other patients completed the protocol. Furthermore, a stimulation protocol similar to ours has been effectively used in many pa,tients with coronary heart disease with and without ventricular tachyarrhythmias3J1 and was also used in 38 patients without detectable heart disease.24In this smaller group of patients 3 or more induced VPCs were never observed. Relation to the results of signal averaging and Holter monitoring: The prevalence of late potentials in patients with IDC has not been studied systematically. This may be because patients with complete bundle branch block were excluded from previously reported studies. In our patient population 31% had left bundle branch block and 26% had a left anterior hemiblock electrocardiographic pattern. Surprisingly, only 1 of the 30 patients studied showed a late potential. He was followed for 12 months and survived. Previous studies have shown that late potentials can be identified in a much larger proportion of patients with documented VT, especially of those with underlying left ventricular akinesia or aneurysm due to coronary artery disease.2-5By definition, none of our patients had such an anatomic substrate. Therefore, we believe that the lack of late potentials in this diseaseis the result of a specific underlying anatomic substrate and that late potentials cannot be used as an indicator of ventricular electrical instability in patients with IDC. Previous studies have also yielded a high incidence of inducible ventricular arrhythmias in patients with and without VT and underlying coronary artery disease. In this study we found, in patients with IDC, no association between spontaneous ventricular arrhythmias and those induced by programmed electrical stimulation using a widespread stimulation protocol applied to the right ventricle. Prognostic significance and ~lin~~a~~m~l~~ations: We previously reported that patients with a severely impaired left ventricular function and many ventricular pairs or episodes of VT are at risk of dying sudden1y.l In this study 1 of 2 patients who died suddenly and 1 of 5 who died of chronic heart failure fulfilled this criterion. Therefore, this measurement, although neither entirely sensitive or specific in the few patients who died, may be the best indicator of the risk of dying suddenly. However, since one-third of the patients had nonsustained VT on ambulatory electrocardiographic monitoring and only 1 of them died suddenly, this variable was insensitive in predicting sudden cardiac death in this group of patients. The results of programmed electrical stimulation in this study indicate a low inducibility of sustained VT in patients with IDC, as well as a lack of prognostic impact of the induced repetitive VPCs (fewer than 6
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repetitive VPCs, nonsustained polymorphic VT and VF). In contrast to patients with coronary artery disease, who either with or without spontaneous VT are highly inducible by similar stimulation protocols,25 programmed electrical stimulation does not serve as an appropriate technique to assessventricular electrical instability in most patients with IDC. References 1. Meinertz T, Hofmann T, Kasper W, Treese N, Be&told f-f, Stienen Lf, Pop 1, Leitner ERV, Andresen D, Meyer J. Significance of ventricular arrhythrnn in idiopathic dilated cardiomyopathy. Am J Cardiol 1984;53:9022. Breithardt G, Becker R, Seipei L, Abendroth RR, Ostermeyer J. Non-invasive detection of late potentials in man-a new marker for ventricular tachycardia. Eur Heart J 1984;2:1-9. 3. Breithardt G, Borggrefe M, Quantius B, Karbenn U, Seipel L. Ventricular vulnerability assessed by programmed ventricular electrical stimulation in patients with and without late potentials. Circulation 1983;68:275281. 4. Breithardt G, Broggrefe M, Karbenn U, Abendroth RR, Yeh HL, Seipei L. Prevalence of late potentials in patients with and withaut ventricular ,,,~,,:~~~~orrelation with angiographic findings. Am J Cardiol 1982; 5. Denes P, Santarelii P, Hauser RG, Uretz EF. Quantitative analysis of the high-frequency components of the terminal portion of the body surface QRS in normal subjects and in patients with ventricular tachycardia. Circulation 1983;67:1129-1138. 6. Ruskin JN, DiMarco JP, Garan H. Out-of-hospital cardiac arrest: eleCtrOphysiologic observations and selection of long-term antiarrhythmic therapy. N Engl J Med 1980;303:607-813. 7. Josephson ME, Horowitz LN, Spielman SR, Greenspan AM. Electrophysiologic and hemodynamic studies in patients resuscitated from cardiac arrest. Am J Cardiol 1980;46:948-955, 8. Kehoe R, Bauernfeind RA, Wyndham CRC, Meyers S, Talana J! Rosen KM. Inducible ventricular tachycardia in patients with out-of-hospital ventricular fibrillation (abstr). Am J Cardiol 1980;45:444. 9. Poll DS, Marchiinski FE, Buxton AE, Doherty JU, Waxman HL, Josephson ME. Sustained ventricular tachycardia in patients with idiopathic dilated cardiomyopathy: electrophysiologic testing and lack of response to antiarrhythmic drug therapy. Circulation 1984;70,3:451-456. IO. Breithardt G, Seipef L, Meyer J, Abendroth RR. Prognostic significance of repetitive ventricular response during programmed ventricular stimulation. Am J Cardiol 1982;49:693-697. 11. Treese N, Roemer A, Zotz R, Kasper W, Meinertz T, Pop T. Repetitive Kammerantwort und linksventrikulaere Wandbewegung bei Patienten mit koronarer Herzerkrankung. 2 Kardiol 1983;72:37-43. 12. Erugada P, Abdoiiah H, Heddle B, Weiiens HJJ. Results of a ventricular stimulation protocol using a maximum of 4 premature stimuli in patients without docbmented or s&.pected ventricular arrhythmias. Am J- Cardiol 1983:52:1214-1218. 13. Oeff M, von Leitner ER, Sthapit 8, Breithardt 0, Borggrefe M, Karbenn U, Meinertz T, Zotz R, Cias W, Hombach V, Hoepp NW. Methods for noninvasive detection of ventricular late ootentials-a comaarative multicenter study (abstr). PACE 1983;8:A-108. 14. Greene Hi, Reid PR, Schaeffer AH. The repetitive ventricular response in man. A predictor of sudden death. N Engl J Med 1978;299:729-734. 15. blamer A, Vohra J, Hunt B, Siomann 0. Prediction of sudden death by electrophysiologic studies in high risk patients surviving acute myocardial infarction. Am J Cardiol 1982:50:223-229. 16. Richards DA, Cody DV, DennIsa AR, Russeff PA, Young AA, Uther JB. Ventricular electrical instability: a predictor of sudden death after myocardial infarction. Am J Cardiol 1983;51:75-80. 17. Greene HL, Reid PR, Schaeffer AH. Mechanism of repetitive ventricular response in man. Am J Cardiol 1980;45:227-232. 16. Raviele A, Francesco DP, Deiise P, Piccolo E. Value of serial electropharmacological testing in managing patients resuscitated from cardiac arrest. PACE 1984;7:850-855. 19. Johnson RA. Paiacios I. Dilated cardiomvooathv ,.I of the adult. N Enal - J Med 1982;307:1651-1058. 20. Wellens HJJ, Durrer DR, Lie Kf. Observations on the mechanisms of ventricular tachvcardia in man. Circulation 1978:54:237-244. 21. Nacarelil G\i, Prystowsky EN, Jackman WM,‘Heger JJ, Rahiily GT, DR. Role of electrophysiologic testing in managing patients who ventricular tachycardia unrelated to coronary artery disease. Am J C 1982;50:165-171. 22. Livelfi FD Jr, Bigger JT Jr, Reiffel JA, Gang ES, Patton JN, No~tbi~n~ Rolnltzky KM, Glikllch JI. Response to programmed stimulation: sensitivity, specificity and relation to heart disease. Am J Cardiol 1982;50:452458. 23. Brugada P, Green NI, Abdoliah H, Weilens HJJ. Significance of ventricular arrhythmias initiated by programmed ventricular stimulation: the importance of the type of ventricular arrhythmia induced and the number of premature stimuli required. Circulation 1984;69:87-92. 24. Treese N, Geibei A, Kasper W, Meinertz T, Pop P, ~e~~~ J. Incidence and clinical significance of repetitive ventricular response in patients without identifiable organic heart disease. Int J Cardiol 1984;6:489-489. of induced ar25. Brugada P, Waidecker 5, Weliens NJJ. Characteristics rhythmias in four subgroups of patients with myocardial infarction (ebstr). Circulation 1984;70:76.
Determinants of Prognosis in Idiopathic Dilated Cardiomyopathy as Determined by Programmed Electrical Stimulation THOMAS MEINERTZ, MD, NORBERT TREESE, MD, WOLFGANG ANNETTE GEIBEL, MD, THOMAS
HOFMANN,
KASPER, MD,
MD, MANFRED ZEHENDER, MD,
DORIS BOHN, MD, TIBERIUS POP, MD, and HANJOERG JUST, MD
The incidence and prognostic significance of electrically induced ventricular arrhythmias were prospectively assessed in 42 patients with idiopathic dilated cardiomyopathy. All patients underwent 24-hour, long-term electrocardiographic (Holter) monitoring and 30 were analyzed by a signal-averag ing vectorcardiographic procedure at entry into the study. Their response to programmed electrical stimulation during basic right ventricular pacing was tnvestigated using 1 and 2 ventricular extrastimuli. A monomorphic tachycardia was not induced in any atient. In 36 patients (66%) polymorphic ventricular arrhythmias were initiated. Three or more induced consecutive ventricular premature complexes occurred in 9 patients (21%), nonsustained polymorphic ventricular tachycardia in 2 (4.6%) and ventricular fibrillation in 1 patient (2.4%). There was no association between electrically induced poly-
morphic ventricular arrhythmias and the degree of impairment of left ventricular function. Furthermore, the incidence of induced ventricular arrhythmias was not related to the Lown grade or to the total number of ventricular premature complexes during Holter monitoring. A late potential was detected by the averaged vectorcardiogram in only 1 of the 30 patients. During follow-up (mean 16 f 7 months) 7 patients died, 5 from chronic congestive heart failure and 2 from sudden cardiac death. No patient .had an electrically induced arrhythmia of 3 or more ventricular premature complexes. Thus, in most patients with idiopathic dilated cardiomyopathy, programmed electrical stimulation of the right ventricle with up to 2 extrastimuli fails to reproduce an electrophysiologic correlate to the frequent ventricular arrhythmias. (Am J Cardiol 1
Recently we reported on the prognostic impact of spontaneous ventricular arrhythmias and hemodynamic variables in 74 patients with idiopathic dilated cardiomyopathy (1DQ.l To identify patients who are at risk for sudden cardiac death, specific criteria for the interpretation of the 24-hour electrocardiogram (EC@) or other techniques capable of detecting ventricular electrical instability are required. Signal averaging of tbe high-frequency components of the QRS complexes
appears to be a promising noninvasive technique for detecting patients at risk of sustained ventricular tachycardia. 2-5 The incidence and clinical significance of these signals in patients with IDC are unknown. Another technique found to be useful to study patients with coronary artery disease and IDC at risk for sudden cardiac death is programmed electrical stimulation of the heart.6-g Whether these techniques can be either useful in a greater population of patients with IDC to evaluate ventricular electrical instability and their degree of susceptibility to die suddenly is not known. This study determines in an unselected group of patients with IDC whether programmed electrical stimulation of the heart, either alone or combined with noninvasive techniques such as signal averaging and Holter monitoring, can be useful to assess the degree of ventricular electrical instability and risk of sudden cardiac death.
From the lnnere Medizin lllV Universitaet Freiburg, Freiburg, and II Medizinische Klinik und Poliklinik, Universitaet Mainz, Mainz, Federal Republic of Germany. Manuscript received January 8, 1985; revised manuscript received March 27, 1985, accepted March 29, 1985. Address for reprints: Thomas Meinertz, MD, lnnere Medizin Ill der Universitaet Freiburg, Hugstetterstr. 55, D-7800 Freiburg, Federal Republic of Germany. 337
338
PROGNOSIS IN IDIOPATHIC DILATED CARDIOMYOPATHY
Methods Forty-two consecutive patients diagnosed as having IDC according to the criteria proposed by Goodwin and Oakley were studied after they gave informed, written consent. The patients represent a subgroup of 74 patients with IDC previously investigate@ and were studied by programmed electrical stimulation only by a later time of admission to our hospital. Thirty-eight patients were men and 4 were women, mean age 45 f 9 years (range 10 to 64). At entry of the study all underwent right- and left-sided cardiac catheterization, including measurements of right and left ventricular pressures, cardiac index, left ventriculography using simultaneous biplane views, and coronary cineangiography. Patients also underwent M-mode and 2-dimensional echocardiography (Varian 3400, transducer 2.25 MHz, 2 cm in diameter, unfocused) and radionuclide angiography (first-pass technique). The clinical, hemodynamic and angiographic criteria for the study patients are as described previous1y.l Electrophysiologic study: Patients were in the postabsorptive and nonsedated state. All antiarrhythmic drugs had been withheld for at least 4 half-lives. A quadripolar catheter (electrode distance 1.0 cm) was introduced into the femoral vein and placed in the right ventricular apex. An intraventricular electrogram was recorded from the proximal 2 poles of the catheter, together with the standard electrocardiographic leads I, aVF and VI. The distal 2 poles of the quadripolar catheter were used for pacing. All signals were recorded simultaneously on a 8-channel jet recorder (Mingograph, Siemens Elema). Programmed electrical stimulation was performed with a conduction system analyzer (Medtronic, 5325). The stimuli were 1.8 ms in duration and twice diastolic threshold (less than 3 mA). The stimulation protocol was the same in all patients and included the introduction of single and double ventricular extrastimuli at a basic drive of 500,600 and 430 ms. After every 8 beats 1 premature stimulus (SZ)was introduced late in diastole and then progressively shortened by lo-ms steps until ventricular refractoriness was reached. Thereafter, S2 was set 20 ms outside the effective refractory period. A second extrastimulus (S3) was added 300 ms after Sz and scanned at lo-ms intervals up to the refractory period of the right ventricle. The endpoints of testing were the initiation of 5 or more nonpaced consecutive ventricular premature complexes (VPCs) or each extrastimulus brought to its refractory period.lOJl Definitions: For the purpose of this study the following definitions were used? Electrically induced ventricular premature complexes-VPCs 0 to 2: up to 2 nonpaced consecutive VPCs; VPCs 3 to 5: 3 to 5 nonpaced consecutive VPCS. HV intervals were not measured and no effort was made to distinguish between intraventricular or bundle branch reentry. Nonsustained
polymorphic
ventricular
tachycardia
(VT)-6 or more VPCs with a rate more than 100 beats/min and a well defined QRS complex in the surface leads with continuous changes in axis and morphology, lasting less than 30 seconds and with no intervention required for termination. Ventricular fibrillation (VF): ventricular arrhythmias with disorganized electrical activity in the surface electrocardiogram and no clear identifiable QRS complexes. The definition of sustained monomorphic VT and sustainment of VT are as reported previously.12 Signal averaging: Determination of late potentials from the body surface with high-gain amplification and the signal technique was performed using the Marquette system. The computer uses a set of 3 bipolar, 3 augmented electrodes to
internally construct 6 leads which represent vectors at 30’ increments in a plane defined by the 3 electrodes.A horizontal plane was formed by VI, Vd and Vs chest leads and the frontal plane was formed by the right and left shoulders and the left inguinal region. In each patient, 256 to 512 consecutivecardiac cycles were summed. By means of a pattern matching technique only cycles that corresponded to more than 95% “fit” were accepted. Thus, noisy, aberrant cycles and ventricular arrhythmias were not averaged. The sampling rate was 2,000 samples/s and the resolution was thus less than 0.5 ms. The trigger point is based on the earliest onset of QRS activity. The total system gain was 1 X 105. Output filtration consisted of a Butterworth low-pass filter for the 300 Hz fixed upper frequency cutoff. High-pass filtration was achieved by 0 phase, P-pole digital filters (Butterworth) at 50,100 and 200 Hz (18 db/octave). The following filter settings were used: 50 to 300 Hz, 100 to 300 Hz and 200 to 300 Hz. The resulting averages were recorded on a 3-channel direct-writing recorder at the basic sensitivities of 4000 mm/mV (high resolution) and 200 mm/mV (low resolution) at a paper speed of 400 mm/s. Late potentials were identified visually in the high-gain averaged recordings as low-amplitude activity appearing at least 10 ms after the end of the QRS complex in the low-resolution ECG. Furthermore, these potentials had to be present in at least 5 of the 12 high-resolution electrocardiographic tracings. Using these criteria for the definition of late potentials, a good correlation between the findings with different averaging techniques has been found.13 Holter monitoring: All patients underwent 24-hour Holter monitoring at entrance into the study. Perpendicular leads approximating leads V2 and Vs were recorded simultaneously. The tapes were analyzed semiautomatically using the Siemens Meditape arrhythmia computer. Then, the recordings were scanned again visually at 60 times and 30 times real speed for detecting complex ventricular arrhythmias (ventricular pairs; VT defined as more than consecutiveVPCs at rates of more than lOO/min). Each arrhythmia event detected was written out in real time on standard electrocardiographic paper. All documented arrhythmias were interpreted by 2 independent cardiologists. The sensitivity and specificity of the Holter analysis has been tested by visual real time analysis and found to be more than 90% for VPCs, ventricular pairs and VT. Statistical methods: All calculations were performed on an Honeywell 66-80 computer using the BMDP program. Most data are expressed as mean f standard deviation; only the arrhythmic variables (VPCs/24 hours, ventricular pairs/24 hours, VT/24 hours) are expressedas median values with the 25th and 75th quantiles because of their asymmetric distribution. The relation between the results of Holter monitoring and of programmed electrical stimulation was analyzed by chi-square analysis and Fisher’s exact test. The relation between repetitive ventricular responses and left ventricular function was analyzed by l-way analysis of variance.
Results Clinical, electrocardiographic and hemodynamic findings: The clinical and electrocardiographicfindings
at entry into the study are summarized in Table I. Programmed ventricular stimulation: The results of programmed ventricular stimulation are shown in Figure 1. In all but 6 patients (86%), a ventricular arrhythmia was induced by programmed electrical stimulation. However, 6 or more consecutive VPCs were induced in only 3 (7%) patients. One patient had VF that required defibrillation and 2 patients had a nonsustained polymorphic VT, which lasted for 8 VPCs in 1 patient and 43 VPCs in the other (mean cycle length
August i, 1985
TABLE I
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Characterization of the 42 Patients by Clinical and Electrocardiographic Criteria
NYHA classification 6 Iii IV Surface ECG LBBB RBBB LAH AF
n
%
c
10 is 43 19
:A 8 13 0 11 8
3.39
NSPVT VFRVR3
2: 19
360 and 195 ms, respectively). A monomorphic type of VT was observed in no patient studied. There was no association between the results of ventricular stimulation and the degree of impairment of left ventricular function (Table II). During programmed electrical stimulation, 43% of the patients received cardioactive medication (digitalis and nitrates). The results of programmed electrical stimulation were not related to this therapy. Holter monitoring: Eighty-eight percent of the patients had ventricular arrhythmias. Nineteen percent had Lown grade III and 19% Lown grade IVA arrhythmias. Thirty-six percent of the patients had VT episodes (Lown IVB), which were sustained in 2 patients (lasting more than 30 seconds). In these 2 patients the left ventricular ejection fraction was 38% and 46%. The ventricular rate during VT ranged from 108 to 223 VPCs/min (mean 153 f 28). Seven of 23 patients with Lown grade IVAIIVB arrhythmias had more than 20 episodes of VT or ventricular pairs during 24 hours. Signal averaging: A late potential was detected by the averaging technique from the body surface in only 1 of the 30 patients studied. The duration of this late potential was less than 20 ms.
Correlation between programmed electrical stimulation and Holter monitoring: The relation between ventricular arrhythmias registrated by the Holter monitoring and the results of programmed electrical stimulation is listed in Table III. No correlation was found between the number of induced VPCs and the grade of ventricular arrhythmia according to the
elation Between the Results Ventricular Function o-2 VPCS Induced
LVEF (%) LVEDVI (ml/m*) LVEDP (mm Hg) Cl (liters/min/m*)
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AF = atrial fibrillation; ECG = electrocardiogram; LAH = left anterior hemiblock; LBBB = left bundle branch block; NYHA = New York Heart Association; RBBB = right bundle branch block.
TABLE II
OF CARDIOLOGY
37f 17 217 f 63 12f8 3.3 f 0.9
FIGURE 1. Results of programmed electrical stimulation in 42 patients with idiopathic dilated cardiomyopathy. RVR O-2 and 3-5 = repetitive ventricular responses of 0 to 2 or 3 to 5 consecutive ventricular complexes; NSPVT = nonsustained polymorphic ventricular tachycardia; VF = ventricular fibrillation.
Lown classification. The incidence of responses lasting 3 to 5 VPCs and VT/VF was similar in patients with Lown grade 0, I and II, III and IVA, and IVB arrhythmias and independent of the number of VPCs observed during Holter monitoring. In none of the 15 patients with clinically documented VT, i.e. Lown grade IVB, was a sustained monomorphic VT induced, neither a polymorphic sequence of more than 6 complexes or VF. Furthermore, the incidence of induced VPCs lasting 3 to 5 complexes as well as nonsustained polymorphic VT and VF was not related to the number of VPCs or to the Lown grade during Holter monitoring. Outcome: The mean follow-up for patients was 16 f 7 months (range 2 to 24) and at least 12 months for all subjects who survived. Five patients died of chronic heart failure and 2 died suddenly from cardiac causes (unexpected death within 1 hour of onset of symptoms). The hemodynamic and arrhythmic variables found in these patients are listed in Table IV. In none was a monomorphic VT induced, nor was a nonsustained polymorphic VT or VF initiated, Furthermore, no abnormal potentials were found at averaged vectorcardiography in this group of patients. All patients who died suddenly and 2 of the patients who died from chronic heart failure had Lown grade IVB arrhythmias. During follow-up no patient received antiarrhythmic or /3-receptor blocking agents. The medication with digitalis,
f programmer 3-5 VPCS Induced 51 173 11 3.7
f6 f 60 f9 f 0.6
Ventricular
Stimulatio
NSPVT, VF Induced 47f 17 160 f 30 6f3 2.8 f 0.7
p Value NS NS NS NS
Comparison between the mean values of the 3 subgroups (PVCs O-2 or 3-5, NSPVT and VF) was performed by using a l-way analysis of variance. Cl = cardiac index; LVEDP = left ventricular end-diastolic pressure; LVEDVI = left ventricular enddiastolic volume index; LVEF = left ventricular ejection fraction; NS = not significant; NSPVT = nonsustained polymorphic ventricular tachycardia; VF = ventricular fibrillation; VPCs O-2 or 3-5 = repetitive ventricular response of 0 to 2 or 3 to 5 consecutive ventricular complexes.
340
PROGNOSIS
TABLE Ill
DILATED
CARDIOMYOPATHY
Relation Between Repetitive Ventricular Response and Arrhythmic Events During 24-Hour Holter Monitoring
Holter/PES induced Lown O-II Lown IWIVA Lown IVB
IN IDIOPATHIC
TABLE IV
Pt
o-2 VPCS Induced
3-5 VPCS Induced
NSPVT, VF
8
1
2
;
i
if
The analysis was performed by chi-square analysis and Fisher’s exact test (x2 = 3.6, not significant). Arrhythmic events were classified according to the Lown classification. NSPVT = nonsustained polymorphic ventricular tachycardia; PES = programmed electrical stimulation; VF = ventricular fibrillation; VPCs O-2 and 3-5 = repetitive ventricular response of 0 to 2 or 3 to 5 consecutive ventricular complexes.
diuretics and nitrates was modified according to the clinical situation. All patients who died had a severe impairment of left ventricular function, with a left ventricular ejection fraction below 30%, a correlation which was found to be significant in the patients with 1DC.l
Discussion This prospective study was directed to answer 3 questions: What is the incidence of ventricular arrhythmias induced by ventricular stimulation in patients with IDC? What is the clinical and prognostic significance of these arrhythmias? What is the relationship between the arrhythmias induced by ventricular extrastimuli and the results of signal averaging and Holter monitoring? Programmed electrical stimulation can reproducibly replicate VT in patients with coronary artery disease suffering clinically from sustained VT. Among patients considered to be at high risk of sudden cardiac death, programmed electrical stimulation has been used,14-l7 especially in patients who survive out-of-hospital cardiac arrest or who have sustained forms of VT.6Js In patients with IDC considered to be at high risk for life-threatening arrhythmias and sudden cardiac death, the experience with programmed electrical stimulation is limited.gJg-22 The main purpose of our study was therefore to apply ventricular stimulation to a larger group of unselected patients with IDC in order to define the incidence and potential prognostic impact of inducible ventricular arrhythmias in this particular population and to compare programmed electrical stimulation with other noninvasive techniques such as Holter monitoring and signal averaging. Incidence and type of repetitive responses induced: Our results show that an electrically induced ventricular arrhythmia of 6 or more PVCs was observed in only 7.1% of patients with IDC. None of these arrhythmias can be considered a “specific” response to uncover an electrophysiologic correlate to the high incidence of ventricular arrhythmias in these patients. The value of VF induced with 1 and 2 extrastimuli is not known in patients with coronary artery disease,12J3,23 and appears more likely to be an unspecific response also in patients with IDC. These data are similar with those reported by Wellens et a120and Nacarelli et a121and suggest a very low rate
1 : : ;
Characterization Follow-Up
Cause of Death SCD SCD CHF CHF CHF CHF CHF
LVEF (% ) 2 :: 22 ::
of Patients Who Died During Lown Class
Induced VPCS
Late Potential
IVB IVB IVB Ill IVA Ill IVB
1
-
0’ 2 2
q
i
-
CHF = chronic heart failure; LVEF = left ventricular ejection fraction; SCD = sudden cardiac death; VPCs = ventricular premature com-
plexes.
of inducibility of sustained episodes of VT in patients who present with IDC. Wellens et a120reported 3 patients with IDC of 50 patients studied because of sustained VT, who, in contrast to patients with coronary artery disease, did not have VT inducible by programmed electrical stimulation. Nacarelli et a121induced a sustained VT in 6 of 37 patients with different types of cardiomyopathy; 30 of these patients had IDC and 25 had documented VT; further detailed informations on VT were not reported. In a more recent study on a selected group of patients with IDC with a mean ejection fraction of 30% and a history of sustained uniform VT, Poll et al9 found an inducibility rate of 100% for sustained monomorphic VT using an extensive left and right ventricular stimulation protocol.g However, 10 of 11 patients required a stimulation mode using 3 extrastimuli, a stimulation site different from the right ventricular apex, left ventricular pacing or the administration of antiarrhythmic agents. The incidence of induced VPCs observed in our study (79% of patients), and the induction of nonsustained polymorphic VT (5%) are a well known phenomenon during programmed electrical stimulation, and have no relation to clinical arrhythmia even in patients with coronary artery disease.12*23924 Our results suggest that these arrhythmias are nonspecific also in patients with IDC. Stimulation protocol: The mode and extent of ventricular stimulation should be considered when analyzing the incidence and significance of induced VPCs. In this study 1 and 2 extrastimuli were introduced during ventricular drive at 3 basic cycle lengths in the right ventricle. This is a simple, however, for the initiation of sustained VT specific protocol, because it has been demonstrated12 that stimulation with more than 2 extrastimuli may result in progressively more nonspecific responses and some “false-positive” results, as well as in an increase in the number of countershocks required to terminate induced arrhythmias. Using such a nonvigorous stimulation protocol the 2 patients with clinically asymptomatic VT during Holter monitoring had no inducible sustained VT. Both of them remained asymptomatic during follow-up. A further aspect we have to consider is the endpoint used during programmed electrical stimulation. In this study we chose the induction of 5 or more nonpaced This will be a matter of VPCs as an endpoint. 3~11p24
August 1, 1965
discussionbecauseof the high-risk profile of this group, but otherwise such patients studied had been asymptomatic with regard to ventricular arrhythmias. However,during this study in only 3 of 42 patients was more ihan 5 VPCs an en,&347 ” I +I, +“V %P”?Fdo ““.&A -Ll-l” tllo Cer- qtimlllqt~rr~ -i --_-_.--.*
protocol (1 patient with VI? and 2 patients with non sustained polymorphic VT), all other patients completed the protocol. Furthermore, a stimulation protocol similar to ours has been effectively used in many pa,tients with coronary heart disease with and without ventricular tachyarrhythmias3J1 and was also used in 38 patients without detectable heart disease.24In this smaller group of patients 3 or more induced VPCs were never observed. Relation to the results of signal averaging and Holter monitoring: The prevalence of late potentials in patients with IDC has not been studied systematically. This may be because patients with complete bundle branch block were excluded from previously reported studies. In our patient population 31% had left bundle branch block and 26% had a left anterior hemiblock electrocardiographic pattern. Surprisingly, only 1 of the 30 patients studied showed a late potential. He was followed for 12 months and survived. Previous studies have shown that late potentials can be identified in a much larger proportion of patients with documented VT, especially of those with underlying left ventricular akinesia or aneurysm due to coronary artery disease.2-5By definition, none of our patients had such an anatomic substrate. Therefore, we believe that the lack of late potentials in this diseaseis the result of a specific underlying anatomic substrate and that late potentials cannot be used as an indicator of ventricular electrical instability in patients with IDC. Previous studies have also yielded a high incidence of inducible ventricular arrhythmias in patients with and without VT and underlying coronary artery disease. In this study we found, in patients with IDC, no association between spontaneous ventricular arrhythmias and those induced by programmed electrical stimulation using a widespread stimulation protocol applied to the right ventricle. Prognostic significance and ~lin~~a~~m~l~~ations: We previously reported that patients with a severely impaired left ventricular function and many ventricular pairs or episodes of VT are at risk of dying sudden1y.l In this study 1 of 2 patients who died suddenly and 1 of 5 who died of chronic heart failure fulfilled this criterion. Therefore, this measurement, although neither entirely sensitive or specific in the few patients who died, may be the best indicator of the risk of dying suddenly. However, since one-third of the patients had nonsustained VT on ambulatory electrocardiographic monitoring and only 1 of them died suddenly, this variable was insensitive in predicting sudden cardiac death in this group of patients. The results of programmed electrical stimulation in this study indicate a low inducibility of sustained VT in patients with IDC, as well as a lack of prognostic impact of the induced repetitive VPCs (fewer than 6
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repetitive VPCs, nonsustained polymorphic VT and VF). In contrast to patients with coronary artery disease, who either with or without spontaneous VT are highly inducible by similar stimulation protocols,25 programmed electrical stimulation does not serve as an appropriate technique to assessventricular electrical instability in most patients with IDC. References 1. Meinertz T, Hofmann T, Kasper W, Treese N, Be&told f-f, Stienen Lf, Pop 1, Leitner ERV, Andresen D, Meyer J. Significance of ventricular arrhythrnn in idiopathic dilated cardiomyopathy. Am J Cardiol 1984;53:9022. Breithardt G, Becker R, Seipei L, Abendroth RR, Ostermeyer J. Non-invasive detection of late potentials in man-a new marker for ventricular tachycardia. Eur Heart J 1984;2:1-9. 3. Breithardt G, Borggrefe M, Quantius B, Karbenn U, Seipel L. Ventricular vulnerability assessed by programmed ventricular electrical stimulation in patients with and without late potentials. Circulation 1983;68:275281. 4. Breithardt G, Broggrefe M, Karbenn U, Abendroth RR, Yeh HL, Seipei L. Prevalence of late potentials in patients with and withaut ventricular ,,,~,,:~~~~orrelation with angiographic findings. Am J Cardiol 1982; 5. Denes P, Santarelii P, Hauser RG, Uretz EF. Quantitative analysis of the high-frequency components of the terminal portion of the body surface QRS in normal subjects and in patients with ventricular tachycardia. Circulation 1983;67:1129-1138. 6. Ruskin JN, DiMarco JP, Garan H. Out-of-hospital cardiac arrest: eleCtrOphysiologic observations and selection of long-term antiarrhythmic therapy. N Engl J Med 1980;303:607-813. 7. Josephson ME, Horowitz LN, Spielman SR, Greenspan AM. Electrophysiologic and hemodynamic studies in patients resuscitated from cardiac arrest. Am J Cardiol 1980;46:948-955, 8. Kehoe R, Bauernfeind RA, Wyndham CRC, Meyers S, Talana J! Rosen KM. Inducible ventricular tachycardia in patients with out-of-hospital ventricular fibrillation (abstr). Am J Cardiol 1980;45:444. 9. Poll DS, Marchiinski FE, Buxton AE, Doherty JU, Waxman HL, Josephson ME. Sustained ventricular tachycardia in patients with idiopathic dilated cardiomyopathy: electrophysiologic testing and lack of response to antiarrhythmic drug therapy. Circulation 1984;70,3:451-456. IO. Breithardt G, Seipef L, Meyer J, Abendroth RR. Prognostic significance of repetitive ventricular response during programmed ventricular stimulation. Am J Cardiol 1982;49:693-697. 11. Treese N, Roemer A, Zotz R, Kasper W, Meinertz T, Pop T. Repetitive Kammerantwort und linksventrikulaere Wandbewegung bei Patienten mit koronarer Herzerkrankung. 2 Kardiol 1983;72:37-43. 12. Erugada P, Abdoiiah H, Heddle B, Weiiens HJJ. Results of a ventricular stimulation protocol using a maximum of 4 premature stimuli in patients without docbmented or s&.pected ventricular arrhythmias. Am J- Cardiol 1983:52:1214-1218. 13. Oeff M, von Leitner ER, Sthapit 8, Breithardt 0, Borggrefe M, Karbenn U, Meinertz T, Zotz R, Cias W, Hombach V, Hoepp NW. Methods for noninvasive detection of ventricular late ootentials-a comaarative multicenter study (abstr). PACE 1983;8:A-108. 14. Greene Hi, Reid PR, Schaeffer AH. The repetitive ventricular response in man. A predictor of sudden death. N Engl J Med 1978;299:729-734. 15. blamer A, Vohra J, Hunt B, Siomann 0. Prediction of sudden death by electrophysiologic studies in high risk patients surviving acute myocardial infarction. Am J Cardiol 1982:50:223-229. 16. Richards DA, Cody DV, DennIsa AR, Russeff PA, Young AA, Uther JB. Ventricular electrical instability: a predictor of sudden death after myocardial infarction. Am J Cardiol 1983;51:75-80. 17. Greene HL, Reid PR, Schaeffer AH. Mechanism of repetitive ventricular response in man. Am J Cardiol 1980;45:227-232. 16. Raviele A, Francesco DP, Deiise P, Piccolo E. Value of serial electropharmacological testing in managing patients resuscitated from cardiac arrest. PACE 1984;7:850-855. 19. Johnson RA. Paiacios I. Dilated cardiomvooathv ,.I of the adult. N Enal - J Med 1982;307:1651-1058. 20. Wellens HJJ, Durrer DR, Lie Kf. Observations on the mechanisms of ventricular tachvcardia in man. Circulation 1978:54:237-244. 21. Nacarelil G\i, Prystowsky EN, Jackman WM,‘Heger JJ, Rahiily GT, DR. Role of electrophysiologic testing in managing patients who ventricular tachycardia unrelated to coronary artery disease. Am J C 1982;50:165-171. 22. Livelfi FD Jr, Bigger JT Jr, Reiffel JA, Gang ES, Patton JN, No~tbi~n~ Rolnltzky KM, Glikllch JI. Response to programmed stimulation: sensitivity, specificity and relation to heart disease. Am J Cardiol 1982;50:452458. 23. Brugada P, Green NI, Abdoliah H, Weilens HJJ. Significance of ventricular arrhythmias initiated by programmed ventricular stimulation: the importance of the type of ventricular arrhythmia induced and the number of premature stimuli required. Circulation 1984;69:87-92. 24. Treese N, Geibei A, Kasper W, Meinertz T, Pop P, ~e~~~ J. Incidence and clinical significance of repetitive ventricular response in patients without identifiable organic heart disease. Int J Cardiol 1984;6:489-489. of induced ar25. Brugada P, Waidecker 5, Weliens NJJ. Characteristics rhythmias in four subgroups of patients with myocardial infarction (ebstr). Circulation 1984;70:76.