Ambulatory electrocardiographic correlates of ventricular inducibility during programmed electrical stimulation

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Ambulatory Electrocardiographic Correlates of Ventricular Inducibility During Programmed Electrical Stimulation ALAN H. GRADMAN, MD, FACe. WILLIAM P. BATSFORD, MD, ELLEN C. RIEUR, BS, LINDA LEON, BA, ALICE M. VAN ZETTA, BS New Haven, Connecticut

To determine the relation between spontaneous and induced ventricular arrhythmias, ambulatory electrocardiographic (Holter) monitoring and programmed electrical stimulation were performed in 48 adult patients with suspected life-threatening ventricular arrhythmias. Nine had no inducible arrhythmia, 11 demonstrated 1 to 2 beats of intraventricular reentry, 19 exhibited nonsustained ventricular tachycardia and 9 exhibited sustained ventricular tachycardia during electrophysiologic studies. Patients without arrhythmia inducibility had a high incidenceof multiformity (56%) and bigeminy (44%), but a low incidence of either couplets (ll %) or spontaneous ventricular tachycardia (11%) on Holter monitoring. An increasing incidence of all "complex" ectopic features was found with increasing degrees of ventricular inducibility. In patients with inducible sustained ventricular tachycardia, multiformity was present in 100%, bigeminy and couplets in 89% and spontaneous ventricular tachycardia in 78%. Premature ventricular complex frequency, couplet frequency and the repetition

Ambulatory electrocardiographic (Holter) monitoring and programmed electrical stimulation are two clinical techniques that are widely utilized to detect cardiac electrical instability, gauge the risk of sudden death and evaluate the results of antiarrhythmic drug therapy. Although previous studies (1,2) indicate that ventricular tachycardia inducibility and the syndrome of recurrent sustained ventricular tachycardia are closely linked, the relation between lesser degrees of ventricular ectopic activity and ventricular response to provocative electrophysiologic testing is unFrom the Cardiology Section. Department of Medicine. West Haven Veterans Administration Medical Center. West Haven. Connecticut and Yale-New Haven Hospital. New Haven. Connecticut. This study was supported in part by a Veterans Administration Merit Review Award from the Research Service of the Veterans Administration Medical Center. West Haven. Connecticut. Manuscript received May 22. 1984; revised manuscript received November 6. 1984. accepted November 26. 1984. Address for reprints: Alan H. Gradman. MD. Cardiology Scction/S? LMP. Yale University School of Medicine. P.O. Box 3333. 333 Cedar Street. New Haven. Connecticut 06510. (J

1985 by tbe American College of Cardiology

index (the ratio of couplets to premature ventricular complexes) were also found to be directly correlated with the degree of ventricular inducibility. Three quantitative arrhythmia variables were identified which predicted ventricular tachycardia inducibility. Seven (78% ) of 9 patients with a mean premature ventricular complex frequency of 100or more/I ,000 normal beats, 11 (85% ) of 13 with a mean couplet frequency of 1 or more/I,OOO normal beats and 19 (83%) of 23 with a mean repetition index value of 15 or morell ,000 premature ventricular complexes proved to have inducible ventricular tachycardia. These data indicate that spontaneous and induced ventricular arrhythmias are related in definable ways, that certain "complex" ectopic features are more specifically correlated with ventricular inducibility than are others and that it is possible using quantitative arrhythmia data to define Holter monitor criteria that, when present, serve as markers of the state of ventricular tachycardia inducibility. (J Am Coli CardioL 1985;5:1087-93)

known. On the basis of data indicating that significant ventricular arrhythmia may persist in some patients in whom ventricular tachycardia inducibility has been abolished by pharmacologic or surgical means, other authors (3,4) concluded that spontaneous and inducible ventricular arrhythmias are essentially independent and unrelated phenomena. Systematic study of their relation in the untreated state has not, however, been reported. In this study, ambulatory electrocardiographic monitoring and programmed electrical stimulation were performed in a group of patients with suspected life-threatening ventricular arrhythmias. The purpose of the study was to explore the relation between spontaneous and induced arrhythmias and determine which ectopic features are most closely correlated with the degree of ventricular arrhythmia inducibility during programmed electrical stimulation. In contrast to previous results, our data indicate that spontaneous and induced ventricular arrhythmias are related in definable ways, that certain "complex" ectopic features are more specifi0735-1097/85/$3.30

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GRADMAN hi AL. HOLTER CORRELATES OF VENTRICULAR INDUCIBILITY

cally correlated with ventricular inducibility than are others and that, using quantitative premature ventricular complex and couplet frequency data, it is possible to define Holter monitor arrhythmia criteria which, when present, serve as reasonably specific predictors of the ventricular tachycardia inducible state.

Methods Study patients. The study group consisted of 48 adult patients (37 men and II women) hospitalized for arrhythmia evaluation at Yale-New Haven Hospital or the West Haven Veterans Administration Medical Center. Their ages ranged from 18 to 89 years (average 57). Twenty-nine had known coronary artery disease, four had cardiomyopathy, six had valvular heart disease (four with mitral valve prolapse and two with other valvular lesions) and one had constrictive pericarditis. Eight patients had no documented anatomic heart disease. Three patients underwent electrophysiologic evaluation after an episode of ventricular fibrillation. Nineteen had a history of sustained ventricular tachycardia. Seven patients had had previous episodes of nonsustained tachycardia observed either during ambulatory electrocardiographic monitoring or treadmill exercise testing. Unexplained syncope or presyncope possibly due to ventricular tachyarrhythmias had been noted in 17 patients. Two patients were studied because of the finding of complex ventricular ectopic beats and the suspicion of ventricular tachycardia. Protocol. Ambulatory electrocardiographic monitoring (mean duration 13.8 hours) was performed before baseline electrophysiologic study. Twenty-three patients had received no antiarrhythmic drugs for at least 48 hours before electrocardiographic monitoring was initiated. In 21 patients, Holter monitor recordings were obtained during the period of withdrawal from one or more antiarrhythmic medications (procainamide in 7, quinidine in 7, disopyramide in 6, lidocaine in 3, phenytoin in 1, mexiletine in 1 and propranolol in 2) before electrophysiologic testing. In these patients, electrocardiographic monitoring was begun as long as practically possible after the final medication dose was given. This interval was more than 24 hours in 10 patients, 12 to 24 hours in 10 and less than 12 hours in I. Two patients were taking quinidine and two were taking a betareceptor blocking agent throughout the study. Electrophysiologic study. Programmed electrical stimulation was performed according to a standard protocol. For ventricular arrhythmia induction, this protocol included single, double and triple premature stimuli delivered from the right ventricular apex both during sinus rhythm and right ventricular pacing (at cycle lengths of 500 or 600 ms, or both). When these approaches failed to induce ventricular tachycardia, rapid right ventricular burst pacing was performed. The stimulation protocol was continued until the maximal or near maximal response was obtained.

Ambulatory arrhythmia detection and quantification. Ambulatory electrocardiographic recordings were analyzed using the YALECG research minicomputer system (5). Currently configured on a Data General Eclipse S/130 processor, the YALECG algorithm is based on a widthsensitive peak detector for location of QRS complexes and a dual-width correlation matching algorithm for waveform comparison. The system is operator-interactive and a series of on-line validity checks are used to ensure optimal program function. The accuracy of this system in detecting premature ventricular complexes has been previously validated (5). The mean frequency of premature ventricular complexes (expressed per 1,000 normal beats) was determined for each Holter monitor recording. The occurrence of two consecutive premature ventricular complexes was defined as a couplet, and couplet frequencies (per 1,000 normal beats) were also determined. The repetition index (R). For each recording, the frequency with which a single premature ventricular complex was followed by a second such complex was calculated as R =

Number of couplets Number of initial premature ventricular complexes'

Initial premature ventricular complexes include all single premature ventricular complexes, as well as those premature ventricular complexes initiating couplets or episodes of ventricular tachycardia. This ratio is defined as the' 'repetition index" and is expressed per 1,000 premature ventricular complexes. Statistical methods. The relation between mean premature ventricular complex frequency, mean couplet frequency, mean repetition index and ventricular inducibility was determined using one-way analysis of variance of the log 10 transformed data. Unpaired t tests (with p values corrected for multiple comparisons) were used to compare any two values. A probability value of less than 0.05 was considered significant.

Results Ventricular inducibility. Patients were classified into four categories based on their response to programmed electrical stimulation. Nine patients were found to have no inducible arrhythmia and II demonstrated a maximum of 1 or 2 beats of intraventricular reentry. Nineteen exhibited 3 to 9 beats of nonsustained ventricular tachycardia. Nine had inducible ventricular tachycardia of 10 beats or more in duration and were classified as having sustained ventricular tachycardia. (Rapid right ventricular burst pacing was used as the mode of induction in 4 [14%] of 28 patients in whom ventricular tachycardia was inducible.) Qualitative arrhythmia features and inducibility. The relation between the presence of the various "complex" ventricular ectopic features and inducibility during pro-

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Table I. Complex Ventricular Arrhythmias and Inducibility

Noninducible Multiformity (n = 42) Bigeminy (n = 34) Couplets (n = 32) Ventricular tachycardia (n

4 of 9 (44%)

10 of II (91%) 7 of II (64%)

lof9(11%) I of 9 (11%)

7 of 11(64%) 6 of II (55%)

5 of 9 (56%)

=

28)

grammed electrical stimulation is given in Table I. Patients with no inducible arrhythmia had a significant incidence of both premature ventricular complex multiformity (56%) and ventricular bigeminy (44%), but a low incidence of either couplets (11 %) or ventricular tachycardia (11 %). With increasing degrees of ventricular inducibility, an increasing incidence of all "complex" ectopic features was observed. Patients with inducible sustained ventricular tachycardia exhibited a very high prevalence of all . 'complex" arrhythmias and, in this subgroup, multiformity was present in 100%, bigeminy in 89%, couplets in 89% and spontaneous ventricular tachycardia in 78%.

Quantitative arrhythmia variables and inducibility. The relation between mean premature ventricular complex frequency and inducibility is shown in Figure I. In the Figure 1. Relation between mean premature ventricular complex

Nonsustained 18 of 16 of 16 of 8 of

Sustained 9 of 9 (100%)

19 (95%) 19 (84%) 19 (84%) 19 (42%)

7 of9 (78%) 8 of 9 (89%)

7 of 9 (78%)

subgroup without inducible arrhythmia, mean premature ventricular complex frequency averaged 6.0 ± 5.0/1,000 normal beats compared with 38 ± 16 beats in patients with intraventricular reentry (p = NS), 89 ± 49 in those with nonsustained ventricular tachycardia (p < 0.01) and 105 ± 45 in those with sustained ventricular tachycardia (p < 0.02). By analysis of variance (ANDV A), the F ratio for these data was 5.698 (p < 0.(05), indicating a highly significant relation between log premature ventricular complex frequency and ventricular inducibility. A similar progressive increase in couplet frequency was observed with increasing severity of induced arrhythmia (Fig. 2). Mean couplet frequency averaged 0.2 ± 0.2 per Figure 2. Relation between mean couplet frequency and the degree of ventricular inducibility. F (log couplet frequency) = 5.820 (p < 0.005). *p < 0.02; **p < 0.005. Abbreviations as in Figure I.

(PVC) frequency and the degree of ventricular inducibility. F (log PVC frequency) = 5.698 (p < 0.005). *p < 0.02; **p < 0.01. IVR = intraventricular reentry; Non -= noninducible; NSVT = nonsustained ventricular tachycardia; SVT = sustained ventricular tachycardia. 160

VentricularTachycardia

Intraventricular Reentry

20

••

n=9

*

n=9

** n=19

140

15

z 0

0

Q ......

120

rn ~

Z

0 0 0

...... u

>

IU

.J

100

Q.

:::> 10 0

U

Z

80

«

a.

w

~

z

«

w

60

~

5

*

40

n=19

20 n= II

a

Non

IVR

NSVT

SVT

Non

IVR

NSVT

SVT

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GRADMAN ET AL. HOLTERCORRELATES OF VENTRICULAR INDUCIBILITY

1,000 normal beats in the patients with no inducible arrhythmia compared with 0.8 ± 0.6 in patients with intraventricular reentry (p = NS), 2.4 ± 1.1 in patients with nonsustained ventricular tachycardia (p < 0.02) and 10.5 ± 6 .8 in those with sustained ventricular tachycardia (p < 0 .(05). The F ratio for this distribution was 5.820 (p < 0.(05) . The relation between the repetition index (R) and ventricular inducibility is shown in Figure 3. Mean repetition index increased from 5.0 ± 5.0 per 1,000 premature ven-

tricular complexes in patients without inducible arrhythmia to 17 ± 6.6 in patients with intraventricular reentry (p = NS), 42 ± 14 in the subgroup with nonsustained ventricular tachycardia (p < 0.(01) and 80 ± 28 in patients with sustained ventricular tachycardia (p < 0.(01). The F ratio

Figure3. Relation between therepetition index (R) and the degree of ventricular inducibility. F (log R) = 8.170 (p < 0.00I). ***p < 0.001. Abbreviations as in Figure 1. n=9

110

*** 100

90

80

70 X I.LI

o Z

***

60

n=19

z

o tt-

50

0::

40

I.LI 0I.LI

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for log repetitionindex was 8.170 (p < O.ool)-the highest of the quantitative arrhythmia variables studied. Predictors of ventricular tachycardia inducibility. Further data analysis revealed that subjects with very high premature ventricularcomplex and couplet frequencies and those with a repetition index of 15 or more usually exhibited ventricular tachycardia inducibility (sustained or nonsustained) during programmed electrical stimulation. Thus, seven (78%) of nine patients with a mean premature ventricular complex frequency of 100 or morel 1,000 normal beats, II (85%) of 13 with a mean couplet frequency of I or morel 1,000 normal beats and 19 (83%) of 23 with a repetition index value of 15 or morel 1,000 premature ventricular complexes demonstrated ventricular tachycardia inducibility. The sensitivity and positive predictive value of these three criteria in predicting ventricular tachycardia inducibility is given in Table 2. Although their predictive value was similar, their sensitivitydiffered markedly. Thus, only 25% of patients with inducible ventricular tachycardia were recognizable through analysisof premature ventricular complex frequency, 39% using couplet frequency and 68% using the repetition index. Twenty (71 %) of the 28 patients with inducible ventriculartachycardiaexhibitedone or more of these predictivearrhythmia variables. Of these, 19 (95%) had a repetition index value of 15 or morel 1,000 premature ventricular complexes. The ability of these criteria to predict ventricular tachycardia inducibility was independently examined in the subset of 17 patients who underwent electrophysiologic study because of suspected ventricular tachycardia, but in whom ventricular tachycardia or fibrillation had never been observed clinically. Fifteen patients had had syncopal or presyncopal episodes and two had had complex ventricular arrhythmia only. At the time of electrophysiologic study, 6 patients had inducible ventricular tachycardia whereas 11 did not. Ventricular tachycardia was not inducible in one patient who had a premature ventricular complex frequency of greater than 10011 ,000 normal beats. One patient with a couplet frequency of greater than 111 ,000 normal beats and two of three with a repetition index. value of greater than 15 had inducible ventricular tachycardia. For the group as a whole, spontaneous ventricular tachycardia, which occurred in 22 (46%) of the 48 study patients, Table 2. Arrhythmia Variables Predictive of Inducible Ventricular Tachycardia (n = 28)

30 n=11

20

PVC frequency ~ 10011 ,000 normal beats (n = 9) Couplet frequency ~ 1/1.000 normal beats (n = 13) R ~ 15/1,000 PVCs (n = 23)

Non

IVR

NSVT

SVT

PVCs

=

Sensitivity

Positive Predictive Value

7 of 28 (25%)

7 of 9 (78%)

II of 28 (39%)

II of 13 (85%)

19 of 28 (68%)

19 of 23 (83%)

premature ventricular complexes ; R

=

repetition index.

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proved to be less reliable than other variables as a predictor of ventricular tachycardia inducibility. Thus, ventricular tachycardia inducibility was noted in 15 (68%) of22 patients with, and 13 (50%) of 26 of those without this arrhythmia during the ambulatory monitoring period.

Discussion Relation between spontaneous and induced ventricular arrhythmias. In this study, the degree of ventricular inducibility during programmed electrical stimulation was correlated with the results of a detailed quantitative analysis of arrhythmias recorded during long-term electrocardiographic monitoring. Our data demonstrate that in this patient group premature ventricular complex frequency, couplet frequency and the repetition index increase directly with increasing severity of ventricular arrhythmia inducibility. In addition, the incidence of those "complex" ectopic features (multiformity, bigeminy, couplets and ventricular tachycardia) previously shown to be risk factors for sudden death was also related to the degree of ventricular inducibility. These data clearly indicate that spontaneous ventricular ectopic activity and inducible ventricular arrhythmias are related phenomena. This viewpoint is at variance with several previous studies that have questioned the association between arrhythmias recorded on the ambulatory electrocardiogram and those occurring in response to programmed electrical stimulation. Herling et al. (3) reported that "complex" ventricular ectopic activity may persist in patients whose ventricular tachycardia inducibility had been abolished surgically and, conversely, that ectopic activity may be suppressed in drugtreated patients exhibiting persistent ventricular tachycardia inducibility. Other investigators (7-11) noted a similar lack of correlation between spontaneous and induced arrhythmias in subjects taking encainide (7) and amiodarone (8-11) and in patients with stable angina, most of whom were receiving beta-adrenergic blocking agents (4). Our own amiodarone data (12) confirm the frequently marked disparity between the effects of this agent in suppressing spontaneous arrhythmias and its effects on ventricular inducibility. However, these studies showing a lack of correlation between electrophysiologic and Holter monitor findings were all performed in patients who either were receiving antiarrhythmic drugs or had had surgical antiarrhythmic therapy. In contrast, our patients were evaluated largely in the untreated state, and this fact may well explain the apparently discordant findings. It is clear from experimental studies that a variety of electrophysiologic derangements, acting alone and in combination, may be responsible for the occurrence of both initial ectopic activity and sustained ventricular arrhythmia. These include abnormalities in automaticity and triggered automaticity, changes in local refractoriness and dispersion of global refractoriness, alterations in conduction velocity and changes in resting mem-

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brane potentials (13). Although it is usually not known which of these factors are operative in producing specific arrhythmias in individual patients, surgical or pharmacologic therapeutic interventions might well be expected to differentially affect these e1ectrophysiologic properties and distort what was a primary relation between spontaneous and induced arrhythmias. Grading ventricular arrhythmia. Our results are useful in assessing the degree to which specific ventricular arrhythmic patterns reflect myocardial electrical instability. Earlier natural history studies (14-19) emphasized the concept of arrhythmia "complexity" and its adverse prognostic implications in patients with coronary artery disease. Arrhythmia "complexity" was variably defined to include premature ventricular complex multiformity, bigeminy, couplets, ventricular tachycardia and early cycle ("R on T") premature ventricular complexes. Our data indicate that multiformity and bigeminy are indeed sensitive markers of cardiac electrical instability that are almost universally present in patients with significant inducible ventricular arrhythmias. These arrhythmia patterns are, however, nonspecific findings which, in our study, were found in a large proportion of patients without any inducible arrhythmia. These results are in agreement with previous work (14,16-18,20) that consistently showed multiformity to be a risk factor for sudden death in susceptible patient groups, but also documented its frequent occurrence in normal patient groups (including normal male medical students) who appear to be at littlerisk for fatal ventricular arrhythmia occurrence (21,22). Spontaneous repetitive arrhythmias (couplets and ventricular tachycardia) proved to be more specific markers of arrhythmia inducibility and in this study were present in only II % of patients without inducible arrhythmia. Holter monitor predictors of inducible ventricular tachycardia. An important result of this study is the definition of three quantitative arrhythmia criteria which, when present, can be used to identify patients likely to demonstrate inducible ventricular tachycardia during programmed electrical stimulation. Patients with a very high premature ventricular complex frequency (2: 100/1 ,000 normal beats), a couplet frequency of I or more/l ,000 normal beats and a repetition index of 15 or more/l ,000 premature ventricular complexes all had an approximately 80% incidence of inducible ventricular tachycardia (sustained or nonsustained). Although the relation of these arrhythmia variables to sudden death has not been evaluated, they appear to identify a patient subset with serious arrhythmia potential. They may also be used clinically to select patients likely to benefit from invasive e1ectrophysiologic studies. Such studies are extremely useful in guiding antiarrhythmic drug therapy (23-25), but only in subjects with inducible ventricular tachycardia in the baseline state. The repetition index. This index, which reflects the frequency of spontaneous repetitive arrhythmia formation, proved to be the arrhythmia variable most directly related

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GRADMAN ET AL. HOLTER CORRELATES OF VENTRICULAR INDUCIBILITY

to arrhythmia inducibility. Its sensitivity in recognizing patients with inducible ventricular tachycardia not only was greater than that of other quantitative arrhythmia variables studied, but also was greater than that of the finding of ventricular tachycardia itself during the electrocardiographic monitoring period. In our previous studies (6), the repetition index was found to be highly variable from subject to subject, was directly correlated with the finding of nonsustained ventricular tachycardia on the same Holter monitor recording and appeared to be predictive of future ventricular tachycardia occurrence. That it is also closely related to ventricular inducibility lends further credence to the view that it is a useful noninvasive indicator of ventricular vulnerability. Limitations. Our data are in no way meant to imply that ambulatory electrocardiographic monitoring and provocative electrophysiologic testing furnish identical or equivalent information. Clearly, the results of these two tests are sometimes discordant. In the present study, 20% of the patients with inducible ventricular tachycardia did not have "malignant" Holter monitor findings, and we observed several patients in whom sustained ventricular tachycardia was inducible in the virtual absence of spontaneous ectopic occurrence during 24 hours of electrocardiographic monitoring. Conversely, we and others (2,24) have followed up patients with spontaneous sustained ventricular tachycardia in whom ventricular inducibility could not be demonstrated despite programmed stimulation of both the right and left ventricles. It appears likely that patients susceptible to serious ventricular arrhythmias fall along a continuum, with some exhibiting either advanced degrees of spontaneous ectopic activity or ventricular inducibility alone while most display both as manifestations of myocardial electrical instability. The group of patients in this study is a highly selected one. Forty-six percent had a history of documented ventricular fibrillation or sustained ventricular tachycardia, and 20% had had nonsustained ventricular tachycardia observed at some point during their clinical course. The degree to which our results apply to other patient groups with a lower prevalence of serious ventricular arrhythmias is unknown. Subgroup analysis performed on the 17 patients who had never had documented ventricular tachycardia suggests that the sensitivity of the Holter monitor inducibility predictors may be somewhat less in such patients. We thank Emmanuel Lerner for aid in statistical analysis, Barry L. Zaret, MD for his thoughtful review of the manuscript and Gail Beer for her expert assistance in manuscript preparation.

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2. Vandepol CJ, Farshidi A, Spielman SR, Greenspan AM, Horowitz LN, Josephson ME. Incidence and clinical significance of induced ventricular tachycardia. Am J Cardiol 1980;45:725-31. 3, Herling JM, Horowitz LN, Josephson ME, Ventricular ectopic activity after medical and surgical treatment for recurrent sustained ventricular tachycardia, Am J Cardiol 1980;45:633-9. 4, Kowey PR, Folland ED, Parisi AF, Lown B. Programmed electrical stimulation of the heart in coronary artery disease. Am J Cardiol 1983;51:531-6. 5. Gradman AH, Lewis JW. YALECG: a new system for computer analysis of ambulatory electrocardiograms. In: Ripley KL, Ostrow HS, eds. IEEE Computers in Cardiology, Long Beach, CA: 1978:221-4. 6. Gradman AH, Harbison MA, Lewis JW. Variability of repetitive arrhythmia formation in patients with chronic ventricular arrhythmias. Am J Cardiol 1981;48:437-42. 7. Duff JH, Roden DM, Rawson AK, Oates JA, Smith RF, Woosley RL. Comparison of the effects of placebo and encainide on programmed electrical stimulation and ventricular arrhythmia frequency. Am J Cardiol 1982;50:305-12. 8, Hamer AW, Fincrman WB Jr, PeterT, Mandel WJ. Disparity between the clinical and electrophysiologic effects of amiodarone in the treatment of recurrent ventricular tachyarrhythmias. Am Heart J 1981;102:922-1000. 9. Waxman HL, Groh WC, Marchlinski FE, et aI. Amiodarone for control of sustained ventricular tachyarrhythmias: clinical and electrophysiologic effects of 5\ patients. Am J Cardiol 1982;50:1066-74.

10. Nademanee K, Hendrickson J, Kannan R, Singh B. Antiarrhythmic efficacy and electrophysiologic actions of amiodarone in patients with life-threatening ventricular arrhythmias. Potent suppression of spontaneously occurring tachyarrhythmias versus inconsistent abolition of induced ventricular tachycardia. Am Heart J 1982;103:950-9. II. Heger 11, Prystowksi EN, Jackman WM, et aI. Amiodarone: clinical efficacy and electrophysiology during long-term therapy for recurrent ventricular tachycardia or ventricular fibrillation. N Engl J Med 1981;305:539-45.

12. Kennedy EE, Batsford WP, Rosenfeld LE, Borstelmann NA, Gradman AH. Predicting therapeutic efficacy with amiodarone: a combined Holter/electrophysiologic approach (abstr). J Am Coli Cardiol 1984;3:605. 13. Singer DH, Baumgarten CM, TenEick RE. Cellular electrophysiology of ventricular and other dysrhythmias. Studies on diseased and ischemic heart. Prog Cardiovasc Dis 1981;24:97-\56. 14. Ruberman W, Weinblatt E, Goldberg 10, Frank CW, Shapiro J. Ventricular premature beats and mortality after myocardial infarction. N Engl J Med 1977;397:750-7. 15. Vismara LA, Amsterdam EA, Mason DT. Relationship of ventricular arrhythmias in the late hospital phase of acute myocardial infarction to sudden death after hospital discharge, Am J Med 1975;59:6-12. 16. Schulze RA Jr, Strauss HW, Pitt B. Sudden death in the year following myocardial infarction: relation to ventricular premature contractions in the late hospital phase and left ventricular ejection fraction, Am J Med 1977:62:192-9, 17. Ruberman W, Weinblatt E, Goldberg 10, Frank CW, Shapiro S, Chaudhary BS. Ventricular premature complexes in prognosis of angina. Circulation 1980;61:1172-8.

18, Califf RM, McKinnis RA, Burks J, et aI. Prognostic implications of ventricular arrhythmias during 24 hour ambulatory monitoring in patients undergoing cardiac catheterization for coronary artery disease. Am J Cardiol 1982;50:23-31.

References

19. Moss AJ. Davis HT, DeCamilla J, Bayer LW. Ventricular ectopic beats and their relations to sudden and non-sudden cardiac death after myocardial infarction. Circulation 1979;60:998-1003.

I. Josephson ME, Horowitz LN, Farshidi A, Kastor JA. Recurrent sustained ventricular tachycardia. I. Mechanisms. Circulation 1978;57:431-40.

20. Kotler MN, Tabatznik B, Mower MM. Tominaga S. Prognostic significance of ventricular ectopic beats with respect to sudden death in the late post-infarction period. Circulation 1973;47:959-66.

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21. Clarke JM, Shelton JR, Hamer J, Taylor S, VenningGR. The rhythm of the normal human heart. Lancet 1976;2:508-12. 22. Brodsky M, Wu D, Denes P, Kanakis C. Rosen KM. Arrhythmias documented by 24 hour continuous electrocardiographic monitoring in 50 male medical students without apparent heart disease. Am J Cardiol 1977;39:390-5. 23. Horowitz LN, Josephson ME, Farshidi A. Spielman SR, Michelson EL, Greenspan AM. Recurrent sustained ventricular tachycardia. 3. Role of the electrophysiologic study in selection of antiarrhythmic regimens. Circulation 1978;58:986-97 .

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24. Mason JW, Winkle RA. Electrode catheter induction of ventricular tachycardia: observationson the technique and its use in choosing and assessingthe efficacyof antiarrhythmicdrugs in patients with recurrent ventricular tachycardia. Circulation 1978;58:971-85. 25. Fisher JD, Cohen HL, Mehra R, Altschuler H, Escher DJW, Furman S. Cardiac pacing and pacemakers . II. Serial electrophysiologic pharmacologictesting for control of recurrent tachyarrhythmias. Am Heart J 1977;93:658-68.