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391
lACC Vol. 17. No.2
February 1991:391-6
ELECTROPHYSIOLOGIC STUDIES
Drug Therapy for Ventricular Tachyarrhythmias: How Many
Electropharmacologic Trials Are Appropriate?
KATHERINE M. KAVANAGH, MD, D. GEORGE WYSE, MD, PHD, FACC,
HENRY J. DUFF, MD, ANNE M. GILLIS, MD, ROBERT S. SHELDON, MD, PHD,
L. BRENT MITCHELL, MD
Calgary, Alberta, Canada
=
To determine how many electropharmacologic drug trials should
be performed to select therapy for patients with ventricular
tachyarrhythmias, the outcome of 150 consecutive patients with
inducible ventricular tachyarrhythmias undergoing serial electropharmacologic testing was examined. The probability of identifying predicted effective therapy (induction of fewer than five
ventricular responses with three ventricular extrastimuli at three
pacing cycle lengths) and the probability of that therapy preventing sustained ventricular tachyarrhythmia recurrences were determined as a function of the number of preceding trials.
The probability (:t SE) of identifying predicted effective therapy by the first trial (0.23 :t 0.03) was significantly higher than
that of the second (0.09 :t 0.04), third (0.08 :t 0.04) and fourth
(0.05 :t 0.04) trials (p 0.001). No patient had predicted effective
therapy identified by subsequent trials. The 2 year actuarial
probability of freedom from sustained ventricular tachyarrhythmias on predicted effective therapy was higher for the first (0.79 :t
0.08), second (0.73 :t 0.13) and third (0.86 :t 0.13) trials than for
the fourth (0.33 :t 0.27) trial (p = 0.02).
Thus, the probability of selecting therapy with long-term
efficacy was highest for the first trial (0.18), intermediate for the
second (0.07) and third (0.07) trials and lowest for the fourth
(0.02) and subsequent (0.00) trials. Accordingly, the electropharmacologic approach to therapy selection should be abandoned
after three unsuccessful trials.
(1 Am Coli CardioI1991;17:391-6)
Natural history studies (1-5) have reported high mortality
rates among patients who have had sustained ventricular
tachyarrhythmias without a reversible cause. However, the
prognosis of such patients is improved with individualized
antiarrhythmic therapy. A recent randomized trial (6) supported the practice of selecting therapy for these patients
using the electropharmacologic approach, which begins with
induction of a patient's tachyarrhythmia by programmed
stimulation. Antiarrhythmic drug therapy is then assessed by
repeat programmed stimulation. The process is repeated
until predicted effective therapy is found. Although precise
end points vary, predicted effective therapy is defined as that
which prevents reinduction of the ventricular tachyarrhythmia (7-17). Such effective therapy is found for <50% of
patients (16-21), and previous studies (9,22-24) have suggested that the probability of finding a predicted effective
therapy decreases after one unsuccessful electropharmacologic trial.
Viable alternative therapies now exist for patients for
whom no therapy is considered effective by the electropharmacologic approach, such as empiric amiodarone therapy
(25), implantable device therapy (26) and ablative therapy
(27,28). Accordingly, when a patient is undergoing electropharmacologic testing, a decision must be made as to how
many trials are appropriate before alternative therapeutic
approaches are considered.
The purpose of this study was to determine the probability of identifying predicted effective antiarrhythmic drug
therapy and the follow-up probability of such therapy preventing sustained ventricular tachyarrhythmia recurrences
as a function of the number of preceding unsuccessful trials.
Such information would determine the appropriate number
of electropharmacologic trials in patients with inducible
ventricular tachyarrhythmias.
From the Departments of Medicine and Pharmacology and Therapeutics.
Foothills General Hospital and University of Calgary, Calgary. Alberta,
Canada. This study was supported by grants from the Alberta Heart and
Stroke Foundation, Calgary. Alberta. Drs. Wyse, Duff and Mitchell are
Scholars, Dr. Gillis is a Clinical Investigator and Dr. Kavanagh is a Fellow of
the Alberta Heritage Foundation for Medical Research, Edmonton. Alberta.
Manuscript received May 16, 1990; revised manuscript received August
14, 1990, accepted August 28, 1990.
Address for reprints: L. Brent Mitchell, MD, Division of Cardiology,
Foothills General Hospital, 1403 29th Street. NW, Calgary. Alberta, Canada
T2N 2T9.
©1991
by the American College of Cardiology
Methods
Study patients and design. The study group consisted of
150 consecutive patients with hypotensive ventricular tachycardia or ventricular fibrillation in the absence of a reversible
cause (electrolyte abnormality, proarrhythmic drug effect,
acute myocardial infarction). These patients had their ther0735-1097/91/$3.50
392
KAVANAGH ET AL.
DRUG TRIALS FOR VENTRICULAR ARRHYTHMIAS
apy selected by the electropharmacologic approach between
February 1983 and July 1989.
After written informed consent was obtained, baseline
studies were performed while the patient was not taking any
antiarrhythmic drug. These studies included radionuclide
angiograms and programmed stimulation studies. Patients
were eligible for the electropharmacologic approach if stimulation reproducibly induced their ventricular tachyarrhythmia. Oral therapy was then initiated and programmed stimulation was repeated under steady state conditions (five
half-lives later). Antiarrhythmic drugs were assessed until
predicted effective therapy was found or a prescribed series
of drug trials had been evaluated. The series included at least
one class Ia agent (quinidine, disopyramide, procainamide),
a class Ib agent (usually mexiletine) and a combination of
class Ia and class Ib agents. If left ventricular function
permitted, the series also included a class Ie agent (usually
propafenone), a class II agent (usually propranolol) and a
class III agent (usually sotalol). Other investigational agents
and combinations of agents were used less frequently.
Ventricular tachycardia was defined as five or more
consecutive ventricular complexes at a rate> 120 beats/min
and was considered sustained when it persisted for ;:::30 s or
required termination because of hemodynamic collapse.
Predicted effective therapy was defined as that which prevented the induction of five or more consecutive beats of
ventricular tachycardia.
Electrophysiologic studies. Transvenous electrode catheters were inserted by the Seldinger technique under local
anesthesia (lidocaine 0.33%). Programmed stimulation was
performed using standard techniques (29). Single, double
and triple extrastimuli were introduced after eight beats of
ventricular pacing at cycle lengths of 600, 500 and 400 ms.
Subsequently, 5 and 15 beats of rapid ventricular pacing at
cycle lengths of 300 to 240 ms (10 ms decrements) were
applied. If ventricular tachycardia was not reproducibly
induced at the right ventricular apex, the pacing protocol
was repeated at the right ventricular outflow tract and, if
necessary, from the left ventricle. The end point of stimulation was completion of the stimulation protocol or reproducible induction of sustained ventricular tachyarrhythmia.
Drug evaluation studies were performed after reinstrumentation (30) by repeating the entire stimulation protocol at the
site permitting reproducible ventricular tachyarrhythmia induction at baseline study.
Statistical analysis. Continuous data (mean values ± I SD)
were compared by using Student's unpaired t test. Proportional data were compared by using the chi-square test.
Cumulative probabilities of identifying predicted effective
therapy as a function of the number of drug trials and of
freedom from sustained ventricular tachyarrhythmias and
sudden death as a function of the follow-up duration were
calculated by the Kaplan-Meier method (31) and are presented as mean values ± I SEE. These probabilities were
compared with use of the generalized Wilcoxon test. The
JACC Vol. 17. No.2
February 1991:391-6
Table 1. Characteristics of 150 Study Patients
Predictive Effective
Therapy
No. of patients
Age (yr)
Male
LVEF
Heart disease
None
ASHD/MI
Other
All Patients
Found
Not Found
150
60 ± 12
128 (85)
0.38 ± 0.15
58
56 ± 15
49 (84)
0.43 ± 0.16
62 ± 10
79 (86)
0.35 ± 0.14
0.01
NS
0.001
9 (16)
38 (66)
11 (19)
1 (I)
86 (93)
5 (5)
<0.001
<0.001
0.009
10 (7)
124 (83)
16 (II)
p Value
92
Data are presented as mean ± 1 SD or number (%) of patients. ASHDI
MI = atherosclerotic heart disease with remote myocardial infarction;
LVEF = radionuclide left ventricular ejection fraction; p Value = comparison
of effective therapy found versus no therapy found.
null hypothesis was rejected when the two-tailed p value was
<0.05.
Results
Study patients. The clinical features of the study patients
are presented in Table I. A mean of 2.6 ± 1.5 different
therapies were tested for each patient (median 3 trials, range
1 to 8). Patients for whom a predicted effective therapy was
found were younger and had a higher left ventricular ejection
fraction than were those for whom no predicted effective
therapy could be identified. Likewise, those for whom a
predicted effective therapy was found were less likely to
have atherosclerotic heart disease with remote myocardial
infarction and were more likely to have either no structural
heart disease or structural heart disease other than atherosclerotic heart disease.
Details of the presenting and induced tachyarrhythmias
are shown in Table 2. The majority (79%) of the 150 patients
Table 2. Presenting and Induced Ventricular Tachyarrhythmias in
150 Patients
Predictive Effective
Therapy
No. of patients
Presenting VT/VF
Nonsust VT
Sust VT
VF
Induced VT/VF
Nonsust VT
Sust VT
VF
All
Patients
Found
Not
Found
150
58
92
32 (21)
86 (57)
32 (21)
17 (29)
26 (45)
15 (26)
15 (16)
60 (65)
17 (18)
0.06
0.01
NS
25 (17)
118 (79)
7 (5)
16 (28)
39 (67)
3 (5)
9 (10)
79 (86)
4 (4)
0.004
0.007
NS
p Value
Data represent the number (%) of patients. Nonsust and Sust VT
nonsustained and sustained ventricular tachycardia, respectively. VF
ventricular fibrillation.
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393
KAVANAGH ET AL.
DRUG TRIALS FOR VENTRICULAR ARRHYTHMIAS
JACC Vol. 17, No.2
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ELECTROPHARMACOLOGIC TRIAL NUMBER
0.20
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Figure 1. Incremental (bar graphs :t 1standard error of the estimate)
and cumulative (dashed line) probability of finding a predicted
effective antiarrhythmic drug therapy for inducible ventricular
tachycardia for serial electropharmacologic drug trials I through 8.
presented with sustained ventricular tachycardia or fibrillation. The others presented with hypotensive symptoms
(syncope in 25 of the 32 patients) and had spontaneous
nonsustained ventricular tachycardia documented at another
time. Regardless of the presenting tachyarrhythmia. programmed stimulation at baseline study induced sustained
ventricular tachycardia in most patients (79%). Patients for
whom predicted effective therapy was found were more
likely to have nonsustained and less likely to have sustained
ventricular tachycardia than were those for whom no predicted effective therapy could be identified. In this regard.
the induced tachyarrhythmia was more discriminating than
was the presenting tachyarrhythmia.
Identification of predicted effective therapy. The electropharmacologic approach identified a predicted effective therapy for 58 of the 150 study patients. Figure I presents the
incremental and cumulative probability of finding a predicted
effective therapy as a function of the number of trials
undertaken. The probability of finding a predicted effective
therapy was 0.23 ± 0.03 for the first. 0.09 ± 0.04 for the
second, 0.08 ± 0.04 for the third and 0.05 ± 0.04 for the
fourth trial. No patient had a predicted effective therapy
found at a fifth or subsequent trial. The probability of finding
such therapy at the first trial was significantly higher than at
subsequent trials (p = 0.001). However. there were no
significant differences among the probabilities of finding a
predicted effective therapy at the second, third and fourth
trials.
The probability of a particular agent or class of agents
being considered effective therapy also showed dependence on
the electropharmacologic trial number. For example, the probability of a class I agent being considered effective therapy was
0.24 (29 of 123 trials) for the first trial and 0.06 (4 of68 trials)for
the second, third and fourth trials combined (p = 0.002). No
patient had a predicted effective therapy with a class I agent
identified at the fifth or subsequent electropharmacologic trials.
This trial dependence of the probability of finding a predicted
effective therapy was not the result of differences in the trough
Figure 2. Actuarial probability of remaining free of sustained ven·
tricular tachycardia, ventricular fibrillation and sudden cardiac
death during follow-up study among patients whose therapy was
predicted to be effective by their first electropharmacologic (I:dotted
line), second (2:dashed line), third (3:solid line) or fourth (4:dashed/
dotted line) trial.
steady-state serum levels obtained. For example, there were
no differences among the concentrations of quinidine (the most
commonly used agent in this study) assessed as the first (9.7 ±
2.8p,molJliter), second (10.0 ± 3.6p,molJliter) or third trial (12.0
± 0.5 p,molJliter) (p > OJ) (reference 6.2 to 15.4 p,molJliter).
Only trials of orally administered drugs were included in
this analysis. Nevertheless. 41 of the 150 patients had 1 to 5
trials (mean 2.7 ± 1.4) of intravenously administered drugs
before the testing of oral agents. Comparing the 41 patients
who had and the 109 patients who had not undergone trials
using intravenously administered drug testing. there were no
significant differences among the incremental probabilities of
finding a predicted effective therapy at the first (0.22 ± 0.Q7
and 0.23 ± 0.04, respectively), second (0.08 ± 0.Q7 and
0.10 ± 0.05. respectively), third (0.12 ± 0.08 and 0.06 ±
0.05. respectively) or fourth (0.07 ± 0.09 and 0.04 ± 0.05,
respectively) trial. Thus, intravenous testing did not increase
the likelihood of identifying an effective oral drug therapy
and did not reduce the number of oral drug trials.
The cumulative probability offinding a predicted effective
therapy was also a function of the ventricular tachyarrhyth·
mia induced at baseline-higher for nonsustained ventricular tachycardia (0.68 ± 0.10) and ventricular fibrillation
(0.64 ± 0.27) than for sustained ventricular tachycardia
(0.38 ± 0.05) (p = 0.003). Nevertheless, the incremental
probability of finding a predicted effective therapy for each
category of inducible ventricular tachyarrhythmia showed
similar dependence on the number of preceding unsuccessful
electropharmacologic trials.
Long-term efficacy of selected therapy. Follow-up probabilities of freedom from recurrent sustained ventricular
tachyarrhythmias and sudden death on drug therapy as a
function of the electropharmacologic trial predicting that
therapy to be effective are shown in Figure 2. The probability of freedom from sustained ventricular tachyarrhythmias
394
KAVANAGH ET AL.
DRUG TRIALS FOR VENTRICULAR ARRHYTHMIAS
and sudden death after 2 years was comparable for drug
therapy predicted effective by the first (0.79 ± 0.08; n = 34),
second (0.73 ± 0.13; n = 12) and third (0.86 ± 0.13; n = 9)
trials. However, the 2 year probability offreedom from these
outcomes in patients receiving therapy predicted to be
effective by the fourth trial was significantly lower (0,33 ±
0.27; n = 3) (p = 0.02).
The long-term efficacy of a predicted effective therapy
was also a function of the category of ventricular tachyarrhythmia induced at the baseline programmed stimulation
study. The 2 year probability of freedom from sustained
ventricular tachycardia or fibrillation tended to be higher for
patients with inducible nonsustained ventricular tachycardia
(0.94 ± 0.06) than for those with inducible sustained ventricular tachycardia (0.69 ± 0.08) or inducible ventricular fibrillation (0.67 ± 0.27) (p = 0.11). However, recurrences in
patients with inducible sustained ventricular tachycardia
were rarely fatal. Accordingly, the 2 year follow-up probability of freedom from sudden cardiac death was higher for
patients with inducible nonsustained ventricular tachycardia
(1.00) and those with inducible sustained ventricular tachycardia (0.89 ± 0.06) than for those with inducible ventricular
fibrillation (0.67 ± 0.27) (p = 0.03).
Identification of therapy with long-term efficacy. The
probability of finding therapy with long-term efficacy at each
trial was determined by the product of the probability of
predicting a therapy to be effective and the probability of
that therapy proving to be effective for the subsequent
2 years. Thus, the probability of finding therapy with longterm efficacy was 0.18 for the first, 0.07 for the second, 0.07
for the third and 0.02, for the fourth trial. No patient had
therapy with long-term efficacy identified at subsequent
trials.
Discussion
This study demonstrates that the probability of finding
antiarrhythmic drug therapy with long-term efficacy by the
electropharmacologic approach for patients with inducible
ventricular tachyarrhythmias is a function of the number of
preceding unsuccessful trials. The probabilities of identifying therapy with long-term efficacy are highest for the first
(0.18), intermediate for the second (0.07) and third (0.07),
and lowest for the fourth (0.02) and subsequent (0.00) trials.
Identification of predicted effective therapy. The probability of finding predicted effective therapy for ventricular
tachyarrhythmias is a function of the number of preceding
failed electropharmacologic trials. The probability of success for the first trial is 0.23 and decreases for the second,
third and fourth trials (0.09, 0.08, 0.05, respectively),
whereas subsequent trials have a very low probability of
success (0.00 in this study). Thus, the number of failed
electropharmacologic trials should be considered one of the
factors that determine the probability of the next trial being
considered effective.
IACC Vol. 17. No.2
February 1991:391-6
Patient variables. The patient variables that were predictors of a successful application of the electropharmacologic
approach in this investigation included young age, good left
ventricular function and absence of structural heart disease,
particularly atherosclerotic heart disease. These observations are in keeping with other investigations (21,24,32)
examining predictive values of patient variables for this
purpose. One predictive factor noted by Swerdlow et al. (21)
was fewer preceding unsuccessful empiric drug trials. This
clinical observation is in keeping with our demonstration
that the probability of identifying a predicted effective therapy is a function of the number of preceding unsuccessful
electropharmacologic trials.
Pharmacologic variables. Antiarrhythmic drugs differ in
their ability to suppress ventricular tachyarrhythmia induction by programmed stimulation (24,33,34). Although the
relative efficacy of each agent has not yet been examined in
a randomized trial, there is agreement that the probability of
a trial being considered effective by the electropharmacologic approach is highest for class Ia drugs, the combination
of class Ia and Ib drugs and sotalol (24,33-36). Accordingly,
these agents are usually evaluated first in clinical practice.
The sequence of antiarrhythmic drug use in the present
investigation mirrored this clinical practice. Furthermore,
for the particular agents used extensively in this investigation, the probability of being considered effective therapy
showed the same dependence on the number of preceding
unsuccessful drug trials as did antiarrhythmic therapy in
general.
The observation that patients with inducible ventricular
tachycardia who respond to therapy are most likely to
respond to the first therapy assessed suggests that a trial of
intravenous therapy at the time of the baseline electrophysiologic study may have predictive value for subsequent oral
trials. Indeed, we (23) and others (9,22,24) previously reported that this is so. However, the data from the present
study indicate that the practice of intravenous drug testing
does not reduce the number of subsequent oral trials required to identify a predicted effective therapy. A potential
rationale for this apparent inconsistency has been previously
reported (22-24), that is, a patient's response to an intravenous trial predicts that patient's eventual response to some
oral agent, but not necessarily to the oral form of the drug
tested during intravenous administration.
Long-term efficacy of selected therapy. The follow-up
probability of freedom from sustained ventricular tachyarrhythmias and sudden death is also dependent on the electropharmacologic trial number predicting the therapy to be
effective. When therapy was considered effective by the
first, second or third trial, the event-free probability at
2 years was approximately 0.80. This degree of long-term
efficacy is comparable with results published previously
(14,19). However, the outcome of patients followed up on
therapy predicted to be effective at the fourth trial was less
acceptable. To our knowledge, this relation has not been
reported previously. The explanation for this finding may
KAVANAGH ET AL.
DRUG TRIALS FOR VENTRICULAR ARRHYTHMIAS
JACC Vol. 17, No.2
February 1991:391-6
reside in Bayes' theorem. As the prevalence of a condition
decreases, the predictive value of an imperfect test deteriorates. In this circumstance, the condition is finding a predicted effective drug therapy and the imperfect test is
electropharmacologic testing. After multiple trials, the probability of false prediction of efficacy exceeds that of true
prediction of efficacy. Thus, if more than three electropharmacologic trials are needed to identify a predicted effective
therapy, the probability of long-term ventricular tachyarrhythmia prophylaxis from that therapy is suspect.
Conclusions. When patients are having a series of electropharmacologic trials to select therapy for their ventricular
tachyarrhythmias, a decision must be made as to how many
trials are appropriate before consideration of alternative
therapeutic approaches. The data from this study provide
direction in that regard. The first trial has the highest
probability of identifying therapy with long-term efficacy
(0.18). Thereafter, the probability of finding therapy with
long-term efficacy decreases to an intermediate level for the
second (0.07) and third (0.07) trials. Subsequent trials have a
very low probability of identifying drug therapy with longterm efficacy. Thus, alternative therapeutic approaches
should be considered for those patients who have not
responded to therapy after three electropharmacologic trials.
Although a case could be made for offering alternative
therapeutic approaches to patients in whom even one electropharmacologic trial has been unsuccessful, this practice
would result in approximately 14% of patients being denied
effective electropharmacologic drug therapy.
We acknowledge the important contributions of Claire Miller, RN. Darlene
Ramadan, RN and the staff of Unit 92 and the Electrophysiologic Laboratory
of the Foothills Medical Center, Calgary, Alberta, Canada.
References
I. Strauss MB. Paroxysmal ventricular tachycardia. Am J Med Sci 1930;
179:337-45.
2. Lundy CJ, McLellan LL. Paroxysmal ventricular tachycardia: an etiological study with special reference to type. Ann Intern Med 1934;7:812-36.
3. Trevor Cooke W, White PW. Paroxysmal ventricular tachycardia. Br
Heart J 1943;5:33-54.
4. Williams C, Ellis LB. Ventricular tachycardia: an analysis of thirty-six
cases. Arch Intern Med 1943;71:137-56.
5. Liberthson RR, Nagel EL, Hirschman JC, Nussenfeld SR. Prehospital
ventricular fibrillation: prognosis and followup course. N Engl J Med
1974;291:317-21.
6. Mitchell LB, DuffHJ, Manyari DE, Wyse DG. A randomized clinical trial
of the noninvasive and invasive approaches to drug therapy of ventricular
tachycardia. N Engl J Med 1987;317:1681-7.
7. Wellens HJ, Schuilenburg RM, Durrer D. Electrical stimulation of the
heart in patients with ventricular tachycardia. Circulation 1972;46:21626.
8. Fisher JD, Cohen HL, Mehra R, Altschuler H, Escher DJW, Furman S.
Cardiac pacing and pacemakers. II. Serial electrophysiologicpharmacologic testing for control of recurrent tachyarrhythmias. Am
Heart J 1977;93:658-68.
9. 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.
395
10. Mason JW, Winkle RA. Electrode-catheter arrhythmia induction in the
selection and assessment of antiarrhythmic drug therapy for recurrent
ventricular tachycardia. Circulation 1978;58:971-85.
II. Josephson ME, Horowitz LN. Electrophysiologic approach to therapy of
recurrent sustained ventricular tachycardia. Am J Cardiol 1979;43:63142.
12. Denes P, Wu D, Wyndham C, et al. Chronic long-term electrophysiologic
study of paroxysmal ventricular tachycardia. Chest 1980;77:478-87.
13. Ruskin IN, DiMarco JP, Garan H. Out of hospital cardiac arrest:
electrophysiologic observations and selection of long-term antiarrhythmic
therapy. N Engl J Med 1980;303:607-13.
14. Mason JW, Winkle RA. Accuracy of the ventricular tachycardiainduction study for predicting long-term efficacy and inefficacy of antiarrhythmic drugs. N Engl J Med 1980;303:1073-7.
15. Horowitz LN, Spielman SR, Greenspan AM, Josephson ME. Role of
programmed stimulation in assessing vulnerability to ventricular arrhythmias. Am Heart J 1982;103:604-10.
16. Morady F, Scheinman MM, Hess DS, Sung RJ, Shen E, Shapiro W.
Electrophysiologic testing in the management of survivors of out-ofhospital cardiac arrest. Am J CardioI1983;51:85-9.
17. Swerdlow CD, Winkle RA, Mason JW. Determinants of survival in
patients with ventricular tachyarrhythmias. N Engl J Med 1983;308:143642.
18. Skale BT, Miles WM, Heger 11, Zipes DP, Prystowski EN. Survivors of
cardiac arrest: prevention of recurrence by drug therapy as predicted by
electrophysiologic testing or electrocardiographic monitoring. Am J Cardiol 1986;57: 113-9.
19. Rae AP, Greenspan AM, Spielman SR, et al. Antiarrhythmic drug efficacy
for ventricular tachyarrhythmias associated with coronary artery disease
as assessed by electrophysiologic studies. Am J CardioI1985;55:1494-9.
20. Roy D, Waxman HL, Kienzle MG, Buxton AE, Marchlinski FE, Josephson ME. Clinical characteristics and long-term followup in 119 survivors
of cardiac arrest: relation to inducibility at electrophysiologic testing. Am
J Cardiol 1983;52:969-74.
21. Swerdlow CD, Gong G, Echt DS, et al. Clinical factors predicting
successful electrophysiologic-pharmacologic study in patients with ventricular tachycardia. J Am Coli CardioI1983;1:409-16.
22. Waxman HL, Buxton AE, Sadowski LM, Josephson ME. The response
to procainamide during electrophysiologic study for sustained ventricular
tachyarrhythmias predicts response to other medications. Circulation
1983 ;67:30-7.
23. Wyse DG, Mitchell LB, Duff HJ. Procainamide, disopyramide and
quinidine: discordant antiarrhythmic effects during crossover comparison
in patients with inducible ventricular tachycardia. J Am Coll Cardiol
1987;9:882-9.
24. Kuchar DL, Rottman J, Berger E, Freeman CS, Garan H, Ruskin IN.
Prediction of successful suppression of sustained ventricular tachyarrhythmias by serial drug testing from data derived at the initial electrophysiology study. J Am Coli CardioI1988;12:982-8.
25. Herre JM, Sauve MJ, Malone P, et al. Long-term results of amiodarone
therapy in patients with recurrent sustained ventricular tachycardia or
ventricular fibrillation. J Am Coli CardioI1989:13:442-9.
26. Fisher JD, Kim SG, Mercando AD. Electrical devices for treatment of
arrhythmias. Am J CardioI1988;61:45A-57A.
27. Morady F, Scheinman MM, DiCarlo LA Jr, et al. Catheter ablation of
ventricular tachycardia with intracardiac shocks: results in 33 patients.
Circulation 1987;75:1037-49.
28. Miller JM. Kienzle MG, Harken AH, Josephson ME. Subendocardial
resection for ventricular tachycardia: predictors of surgical success.
Circulation 1984;70:624-31.
29. Mitchell LB. Wyse DG, Duff HJ. Programmed electrical stimulation
studies for ventricular tachycardia induction in humans. I. The role of
functional refractoriness in tachycardia induction. J Am Coll Cardiol
1986;8:567-75.
30. Duff HJ, Mitchell LB, Wyse DG. Programmed electrical stimulation
studies for ventricular tachycardia induction in humans. II. Comparison
of indwelling electrode catheter and daily catheter replacement. J Am Coli
CardioI1986;8:576-81.
31. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457-81.
32. Spielman SR, Schwartz JS, McCarthy DM, et al. Predictors of the
success or failure of medical therapy in patients with chronic recurrent
396
KAVANAGH ET AL.
DRUG TRIALS FOR VENTRICULAR ARRHYTHMIAS
sustained ventricular tachycardia: a discriminant analysis. J Am Coli
CardioI1983;1:401-8.
33. Mason JW, Swerdlow CD, Winkle RA, et al. Ventricular tachyarrhythmia
induction for drug selection: experience with 311 patients. In: Lucchesi
BR, Dingell JV, Schwarz RP Jr, eds. Clinical Pharmacology of Antiarrhythmic Therapy. New York: Raven. 1984;229-39.
34. Rae AP, Greenspan AM, Spielman SR, et al. Antiarrhythmic drug efficacy
JACC Vol. 17. No.2
February
1991 :391-6
for ventricular tachyarrhythmias associated with coronary artery disease
as assessed by electrophysiologic studies. Am J Cardiol 1985;55: 1494-9.
35. Duff HJ. Mitchell LB, Manyari D, Wyse DG. Mexiletine-quinidine
combination: electrophysiologic correlates of a favorable antiarrhythmic
interaction in man. J Am Coil CardioI1987;1O:1I49-56.
36. Nademanee K. Feld G, Hendrickson J, Singh PN, Singh BN. Electrophysiologic and antiarrhythmic effects of sotalol in patients with lifethreatening ventricular tachyarrhythmias. Circulation 1985;72:555-64.