| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 1995;91:1988-1995.)
© 1995 American Heart Association, Inc.
Articles |
Significance and Incidence of Concordance of Drug Efficacy Predictions by Holter Monitoring and Electrophysiological Study in the ESVEM Trial
From the Departments of Medicine, University of Colorado Health Sciences Center, Denver (M.J.R., D.E.M.); College of Physicians and Surgeons of Columbia University, New York, NY (J.E.R.); and University of Arizona, Tucson (E.H., V.H.).
Correspondence to Michael J. Reiter, MD, PhD, Division of Cardiology, B-130, University of Colorado Health Sciences Center, 4200 E 9th Ave, Denver, CO 80262.
 |
Abstract |
|---|
 Top Abstract IntroductionMethods Results Discussion References |
|---|
Background Selection of antiarrhythmic therapy may be based on either suppression of spontaneous ventricular arrhythmias assessed by Holter monitoring or by suppression of inducible ventricular arrhythmias during electrophysiological study. This study examines the frequency and significance of concordance of these two approaches in the Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM) trial.
Methods and Results Twenty-four-hour Holter monitoring was performed in patients randomized to the electrophysiology limb of the ESVEM study at the time of the first drug trial and at the time of an effective drug trial. Holter monitors were available in 65% (146/226) of patients at the time of the first drug trial and in 93% (100/108) of patients at the time of an electrophysiology study predicting drug efficacy. There were no clinical differences between patients who had and those who did not have a Holter monitor. At the time of the first drug trial, concordance of Holter and electrophysiological predictions of drug efficacy was observed in 46% of patients (both techniques predicted efficacy in 23%; neither predicted efficacy in 23%). Discordant results were observed in 54% (Holter suppression without electrophysiological suppression in 44%; electrophysiological suppression without Holter suppression in 10%). At the time of an electrophysiology study predicting drug efficacy, 68 of the 100 patients without inducible ventricular tachyarrhythmias also had suppression of spontaneous ventricular arrhythmias on the Holter recorded at the time of the electrophysiological study. Neither arrhythmia recurrence nor mortality was significantly different in patients with suppression of both inducible and spontaneous ventricular arrhythmias compared with those with only suppression of inducible arrhythmias. Comparison of patients with suppression of both inducible and spontaneous ventricular arrhythmias with the 188 patients in the Holter limb, in whom efficacy was predicted by Holter monitoring only, revealed no difference in outcome.
Conclusions In this population, (1) there is frequent discordance in prediction of drug efficacy and inefficacy between electrophysiological study and Holter monitoring; (2) a requirement to fulfill both Holter and electrophysiological efficacy criteria reduces the number of patients with an efficacy prediction; and (3) suppression of both spontaneous ventricular ectopy and inducible ventricular tachyarrhythmias does not identify a group with better outcome.
Key Words: antiarrhythmic agents • arrhythmia • electrophysiology
|
Introduction |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Antiarrhythmic agents are prescribed for the majority of patients with sustained ventricular arrhythmias, either as primary therapy or as secondary therapy in patients with implanted cardioverter/defibrillators.1 Selection of a specific antiarrhythmic agent is often arbitrary, with efficacy subsequently defined by either suppression of spontaneous ventricular ectopy assessed by Holter monitoring2 or suppression of inducible ventricular arrhythmias assessed by electrophysiological evaluation.3
Comparative predictive accuracy and correlation of these two
intrinsically different methods have not been extensively
studied.4 5 6 Recently, the ESVEM trial
described outcomes
in patients in whom drug efficacy was predicted by Holter monitoring
and by electrophysiological study.7 In this trial,
patients with both frequent spontaneous ventricular arrhythmias (
10
premature ventricular contractions per hour) and inducible sustained
ventricular arrhythmias were randomized to have antiarrhythmic drug
efficacy defined either by Holter monitoring and exercise testing or by
electrophysiological study. Patients then received a randomized series
of antiarrhythmic agents until one was predicted efficacious by the
assigned method. The ESVEM study demonstrated that there were no
significant differences in the rate of arrhythmia recurrence or death
in patients with drug efficacy defined by Holter monitoring compared
with patients with drug efficacy defined by electrophysiological
study.7
No direct correlation of Holter monitoring and electrophysiological evaluation in the same patient was reported in the ESVEM study. However, by design, 24-hour Holter ECG recordings were obtained in patients randomized to the electrophysiology limb at the time of the first drug trial. These Holter monitors were not used to guide therapy but rather were obtained to examine the frequency of concordant efficacy predictions by the two methods. Holter monitors were also recorded at the time of an efficacious drug trial. These Holters were used in a separate analysis to determine the clinical significance of a combined definition of drug efficacy by the two methods. We present the results of these analyses in this article.
|
Methods |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Patient Population
The ESVEM trial was a prospective, multicenter study. Details of the trial design have been published.8 Briefly, patients with documented sustained ventricular arrhythmias, resuscitation from cardiac arrest, or syncope (with subsequent inducible ventricular tachycardia) who lacked exclusion criteria8 (n=1503) and who gave informed consent (n=1005) underwent baseline electrophysiological study and 48 hours of Holter monitoring. Those who had both reproducibly inducible, sustained (
15 seconds) ventricular
tachyarrhythmias and an average of 10 premature ventricular
contractions per hour (n=486) were randomly assigned to undergo testing
of drug efficacy by either serial electrophysiological studies (n=242)
or Holter monitoring (n=244). After randomization to a specific method of defining drug efficacy, patients received, in random order, up to six of seven antiarrhythmic agents (imipramine, mexiletine, pirmenol, procainamide, propafenone, quinidine, or sotalol) at levels defined by protocol.8 Serial electrophysiological or noninvasive drug efficacy assessments were performed until a drug was predicted effective or until all available study drugs were tested. In patients randomized to drug assessment by electrophysiological study, 24-hour Holter monitors were obtained at the time of the first drug trial. In addition, 24-hour Holter monitoring was also performed after electrophysiological study had defined a drug as being efficacious and before hospital discharge. These Holter monitors were not analyzed before discharge.
Analyses
Data obtained at the time of the first drug trial
were used to
determine the frequency of concordance and to determine clinical
predictors of concordance or discordance between the two drug
assessment techniques. Data obtained at the time of an effective drug
trial were used to assess differences in outcome between patients who
met both electrophysiological and Holter criteria of drug efficacy,
those who met only electrophysiological criteria (ie, without
concomitant suppression of spontaneous arrhythmias), and patients in
whom drug efficacy was predicted by Holter monitoring alone.
Holter Analysis
Holter monitoring consisted of continuous
two-channel recordings
in which a minimum of 20 analyzable hours was required except at
baseline, when a minimum of 40 hours was required. All Holter tapes
were analyzed by a centralized tape analysis system (Personal
Computers for Medicine) at the University of Utah. Analysis
reproducibility was assessed by rescanning 9% of all tapes from
December 1989 until trial completion. Reproducibility (mean percent
difference in premature ventricular contraction counts between two
scans of the same tape) was within 1.4%. Count accuracy was assessed
by hand-counting full disclosure printouts of another 2% of tapes.
Accuracy of total premature ventricular contraction counts (mean
difference between scanned and hand counts) averaged 1.0±2.1%
(mean±SEM).
Definition of Drug Efficacy
Holter monitor criteria for drug
efficacy in ESVEM were
defined8 as 70% reduction in premature ventricular
contractions, 80% reduction in ventricular pairs, 90% reduction
in ventricular tachycardia (3 to 15 beats), and elimination of
ventricular tachycardia >15 beats. In addition, the absence of
ventricular tachycardia 5 beats was required during exercise testing.
The same criteria were used for the present study. Drug efficacy
for patients randomized to the electrophysiology study limb required
failure to induce ventricular tachycardia >15 beats with at least two
ventricular extrastimuli at the right ventricular apex at multiple
cycle lengths.8 In patients in whom a second pacing site
or third extrastimulus was required for induction of a sustained
arrhythmia during the baseline study, the same protocol was used for
drug assessments.
Follow-up
Patients were seen 1, 3, and 6 months after
discharge and then
twice annually. Follow-up consisted of symptom assessment, physical
examination, drug plasma concentration determination, and a 24-hour
Holter monitor. End points defining drug failure were sudden death,
cardiac arrest, documented ventricular tachycardia >15 beats,
unmonitored syncope without other explanation, or torsade de
pointes.
Statistical Analysis
Clinical characteristics of patients
were compared by a
two-tailed Fisher's exact test or a 
2 statistic
(for categorical data) and a standard t test or
nonparametric test (for continuous data). Concordance between Holter
monitoring and electrophysiological techniques was assessed with
McNemar's test.9 The influence of clinical
characteristics on concordance was evaluated by logistic regression
analysis.10 Multivariate models were constructed by
backward elimination stepwise procedures, starting with all univariate
predictors significant at P<.25. Cumulative estimates of
arrhythmia recurrence and mortality end points (all-cause, cardiac, and
arrhythmic death) were summarized by Kaplan-Meier actuarial
methods,11 and actuarial outcomes were compared by a
log-rank test or multivariate Cox proportional-hazards regression
models12 after adjustment for covariates8
(presenting arrhythmia, frequency of premature ventricular
contractions, symptom-activity scale class of Goldman et
al,13 enrolling center, underlying cardiac disease,
failure of previous antiarrhythmic drug therapy, and treatment with
sotalol). The data were analyzed with SAS software.14 A
value of P<.05 was considered statistically
significant.
|
Results |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Concordance of Holter and Electrophysiological Evaluations: First Drug Study
Of the 242 patients assigned to have drug efficacy defined by serial electrophysiological studies, 226 underwent at least one restudy on drug. The other 16 patients did not undergo electrophysiological study because of either premature drug failure before assessment for all drugs taken (6 patients), patient withdrawal after premature drug failure on one or more drugs (8 patients), or withdrawal before drug administration (2 patients). Holter monitors were available in 65% (146/226) of these patients at the time of the first electrophysiological drug assessment. No Holter recording was available for analysis in 80 patients either because of technical difficulties (4 patients) or because continuing ineffective therapy while monitoring would interfere with clinical care (76 patients). There were no clinical differences between patients who did and did not have a Holter monitor.
Of 146 patients in whom Holter monitoring data
were available, 48
(33%) met electrophysiological criteria for drug efficacy, and 97
(66%) met Holter efficacy criteria on the initial drug trial
(P<.001; Fig 1
). The Holter monitoring and
electrophysiological techniques were concordant in 46% of patients,
half with concordant predictions of drug efficacy and half with
concordant predictions of drug inefficacy. Seventy-five patients (54%)
had discordant electrophysiological and Holter results, 64 of whom were
suppressed by Holter but not by electrophysiological criteria. Fifteen
of the 49 patients (31%) who did not have suppression of spontaneous
ventricular ectopy met electrophysiological criteria for drug efficacy.
The sensitivity of Holter monitor suppression in predicting
electrophysiological suppression was 0.69, but the specificity of
Holter nonsuppression in predicting electrophysiological inducibility
was only 0.35.
|
Patients with concordant drug efficacy (positive
concordance), patients
with concordant drug inefficacy (negative concordance), and those with
discordant electrophysiological and Holter results were similar in most
baseline clinical characteristics (Table 1), but
multivariate analysis did identify predictors of the two types of
concordance (positive and negative). Since the importance of the
predictors varied for positive and negative concordance, individual
regression models were used instead of one model with a polytomous
outcome. Sotalol therapy was the only clinical characteristic possibly
associated with positive concordance (odds ratio, 2.37; 95% CI, 0.98
to 5.72). Cause of disease other than coronary artery disease (odds
ratio, 3.07; 95% CI, 1.05 to 9.02) and left ventricular ejection
fraction <25% (odds ratio, 2.73; 95% CI, 1.06 to 7.01) were
significant predictors of concordant drug inefficacy.
|
Because the
Holter monitor criteria for declaring drug efficacy in the
ESVEM trial may have been less stringent than criteria used in other
published series,15 we retrospectively analyzed the
frequency of concordance using two additional Holter criteria of drug
efficacy: (1) 70% suppression of premature ventricular contractions,
80% suppression of pairs, and elimination of ventricular tachycardia
3 beats in duration and (2) 80% suppression of premature
ventricular contractions, 90% suppression of pairs, and elimination
of ventricular tachycardia 3 beats in duration. Efficacy by Holter
monitor was achieved in 66% with the original criteria, in 61% with
the first revised criteria, and in 54% with the second revised
criteria. Similar proportions of concordance (46%, 43%, and 46%,
respectively) were observed for the original and the two additional
Holter criteria, with sensitivity of Holter monitor efficacy in
predicting electrophysiological efficacy decreasing but specificity in
predicting electrophysiological inducibility increasing with the more
stringent criteria (Fig 1
).
Twenty-nine patients who underwent repeated electrophysiological evaluations without definition of an effective antiarrhythmic agent had a 24-hour Holter recorded at the time of the last available (and ineffective) antiarrhythmic agent. Of these 29 patients, Holter monitoring predicted drug efficacy in 15 patients (52%).
Significance of Concordant Holter and Electrophysiological
Evaluations: Effective Drug Study
Holter monitors were available for
analysis in 100 of 108
patients (93%) at the time of an electrophysiological study that
predicted drug efficacy. Forty-six of these 100 patients met efficacy
criteria on the first drug exposure, as described above. Two patients
who met electrophysiological efficacy criteria at the time of first
drug exposure had the drug discontinued because of side effects after
discharge and were not included in this outcome analysis on this
drug. The outcome of patients who met electrophysiological efficacy
criteria was not influenced by whether electrophysiological efficacy
was met on the first or subsequent drug trials (P=.790).
Therefore, for the remainder of the analysis, these patients were
pooled.
In the 100 patients who met electrophysiological criteria of
drug
efficacy, 68% also met Holter criteria for drug efficacy on the Holter
obtained before discharge. Patients who met electrophysiological but
not Holter criteria for drug efficacy were more likely to have
presented with ventricular fibrillation or sudden death (38%) than
were patients with suppression of both inducible and spontaneous
arrhythmias (12% of whom presented with ventricular fibrillation
or sudden death; P=.006). No other clinical characteristic
or the antiarrhythmic agent being evaluated affected the incidence of
concordant drug efficacy definitions by both electrophysiological and
Holter criteria (Table 2) by univariate analysis,
although multivariate analysis identified both presenting
arrhythmia and cause of disease to be significant predictors of
suppression of both inducible and spontaneous ventricular arrhythmias
(P=.001). The odds of suppression of both inducible and
spontaneous ventricular arrhythmias for patients without ventricular
fibrillation or sudden death compared with those with this
presenting arrhythmia were 5.03 (95% CI, 1.73 to 14.59), and the
odds ratio for patients with coronary artery disease compared with
those without it was 3.14 (95% CI, 1.12 to 8.82). An antiarrhythmic
drug was predicted to be effective in 45% of patients (108/242)
randomized to undergo electrophysiological evaluation.7 If
suppression of both inducible and spontaneous arrhythmias was required
for a definition of drug efficacy, the proportion of patients for whom
drug efficacy was predicted would decrease to 30%.
|
There was no
significant difference (P=.664) in arrhythmia
recurrence for patients who met both electrophysiological and Holter
criteria for drug efficacy (n=68) compared with those who met
electrophysiological but not Holter criteria (n=32) (Fig
2). There was no significant difference in the type of
end point or arrhythmia recurrence (ie, sudden death, cardiac arrest,
sustained ventricular tachycardia requiring therapy, nonsustained
tachycardia >15 beats, unwitnessed syncope) in patients who met both
criteria compared with those who met electrophysiological but not
Holter criteria. Arrhythmia-free survival for patients with suppression
of both inducible and spontaneous ventricular arrhythmias was 71%,
35%, and 28% at 1, 3, and 5 years, respectively. In patients rendered
noninducible but without suppression of spontaneous ventricular ectopy,
arrhythmia-free survival at 1, 3, and 5 years was 68%, 40%, and 34%,
respectively. Using more stringent criteria for Holter suppression did
not influence the similar outcomes in the two groups. In addition,
comparison of patients in the electrophysiological limb who fulfilled
both electrophysiological and Holter criteria for drug efficacy with
patients in the Holter limb in whom efficacy was guided by Holter
monitoring alone (n=188) revealed no outcome differences
(P=.867) (Fig 3).
|
|
There were no significant differences in the three mortality end points (all-cause, P=.105; cardiac, P=.127; arrhythmic, P=.221) in patients who met both electrophysiological and Holter criteria for drug efficacy compared with those who met electrophysiological but not Holter criteria. Survival for patients with suppression of both inducible and spontaneous ventricular arrhythmias was 88%, 68%, and 59% at 1, 3, and 5 years. In patients who met electrophysiological but not Holter criteria, survival at 1, 3, and 5 years was 96%, 83%, and 71%, respectively. Additionally, there were no significant differences in mortality (all-cause, P=.143; cardiac, P=.247; arrhythmic, P=.323) among electrophysiological study limb patients who met both electrophysiological and Holter criteria for drug efficacy compared with patients in the Holter monitor limb who met efficacy criteria. Survival for the patients in the Holter limb was 89%, 79%, and 67% at 1, 3, and 5 years, respectively.
For 39 patients in whom sotalol was predicted efficacious by electrophysiological study and in whom a Holter tape was available, there was no significant difference in arrhythmia recurrence (P=.723), all-cause mortality (P=.156), cardiac mortality (P=.192), or arrhythmic death (P=.245) between patients who met (n=29) compared with those who did not meet (n=10) Holter criteria for drug efficacy.
|
Discussion |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
We observed a significant discordance between electrophysiological and noninvasive assessments of drug efficacy in the ESVEM trial but, most importantly, did not find that suppression of both spontaneous ventricular ectopy and inducible ventricular tachyarrhythmias predicted a better outcome than suppression of either spontaneous or inducible ventricular arrhythmias alone. Discordance between Holter monitor and electrophysiological results has been reported previously for class Ia,16 17 Ib,18 and III5 19 20 antiarrhythmic agents. In the previous studies, as in the present study, discordance was due primarily to suppression of spontaneous arrhythmias without a prediction of efficacy by electrophysiological study. This observation was interpreted to result from a combination of nonspecificity (excessive "strictness") of programmed stimulation and insensitivity (excessive "leniency") of Holter monitoring.16 However, the comparable outcomes in patients with concordant and discordant results observed in the present study and the similar outcomes in patients with therapy guided by either Holter monitoring or electrophysiology studies7 are not consistent with this interpretation.
Comparable outcomes in patients whose therapy is guided by Holter monitoring or electrophysiological study could occur if each technique identifies an effective agent but a different therapeutic effect. It has been suggested20 21 22 that the spontaneous occurrence of a sustained ventricular arrhythmia requires both an anatomic substrate (ie, reentry circuit) and a trigger to initiate tachycardia (eg, spontaneous ventricular ectopy). Suppression of ventricular ectopy by an antiarrhythmic drug (identified by Holter monitoring) may decrease the occurrence of sustained ventricular arrhythmias by decreasing the frequency of the trigger. Suppression of inducible ventricular arrhythmias at the time of electrophysiological study, on the other hand, may identify effects of an antiarrhythmic drug on the reentry circuit. On the basis of this thesis, it has been suggested22 that patients in whom an antiarrhythmic agent had beneficial effects on both substrate and trigger would do better than patients with only electrophysiological suppression. The observation that patients who met both electrophysiological and Holter criteria for drug efficacy were similar in terms of arrhythmia recurrence and survival compared with patients with only electrophysiological suppression does not support this hypothesis. Our data suggest that electrophysiological and noninvasive approaches are not complementary in the selection of effective antiarrhythmic therapy.
Implications of the Present Analysis for the ESVEM Study
The
ESVEM trial has received significant attention because of the
important implications this study has for clinical practice. It has
been suggested21 that the results of this trial were
misleading, in part because the outcome of patients whose therapy was
defined by electrophysiological study in the ESVEM study was not as
good as previously reported for some electrophysiologically guided
trials. One potential explanation for this difference is that in the
previous trials, drug efficacy was evaluated electrophysiologically
only after formal or informal assessment of the effect of the
antiarrhythmic agent on spontaneous arrhythmias. For example, many
electrophysiologists would not restudy a patient on antiarrhythmic
therapy if telemetry revealed frequent ventricular ectopy or
nonsustained ventricular tachycardia. If this practice is widespread,
many patients with efficacy predicted by electrophysiological study
reported in previous trials may in reality be both
electrophysiologically and noninvasively suppressed. Since patients in
the ESVEM study whose therapy was defined by electrophysiological
restudy were not "prescreened," their outcome could conceivably
be worse than "electrophysiologically guided" patients in the
literature. However, patients who fulfilled both Holter and
electrophysiological criteria of drug efficacy in the present study
would then be expected to have a better outcome than patients without
Holter monitor suppression, and this was not observed.
In light of these observations, the similar outcomes of patients with therapy guided by either invasive or noninvasive techniques may have at least two other alternative explanations: (1) additive effects of the two techniques are too small to be detected in our sample size (this analysis had a power of 0.84 at a two-tailed significance level of .05 to detect a difference of 50% in the actuarial probability of arrhythmia recurrence between patients who were electrophysiologically suppressed with Holter suppression versus those without Holter suppression and a power of 0.79 to detect a 25% difference between patients who were electrophysiologically suppressed with Holter suppression versus patients randomized to the Holter limb who met efficacy criteria for suppression of spontaneous ectopy) or do not occur, or (2) neither technique identifies an effective therapy.21
The risk of arrhythmia recurrence in the ESVEM trial was significantly lower in patients who received sotalol than in those who received other antiarrhythmic agents.23 The recurrence benefit of sotalol was apparent regardless of the method used to determine drug efficacy. In the present analysis, the outcomes of patients treated with sotalol (ie, who met electrophysiological criteria of drug efficacy) were similar regardless of whether or not there was suppression of spontaneous ventricular arrhythmias. Thus, it does not appear that the lower arrhythmia recurrence seen in patients receiving sotalol is related to achievement of greater concordance of electrophysiological and Holter suppression.
Limitations
This study has several potential limitations. Not
all patients
underwent monitoring at the time of the first or the effective
electrophysiological study. At the time of the first
electrophysiological evaluation, 80 patients did not receive a 24-hour
Holter. In the majority, electrophysiological evaluation was
ineffective and Holter recordings were not obtained because it was
thought to be inappropriate to continue ineffective therapy during the
recording of this additional Holter monitor. Although these omissions
might change the exact incidence of concordance, we do not believe this
to be a serious limitation, since the patients who did undergo
monitoring were not distinguishable clinically from those who did
not.
These results are specific to the patient population in the ESVEM study (ie, patients with both frequent premature ventricular contractions and inducible ventricular arrhythmias) and to the methods and suppression criteria used. The extent to which these results can be generalized to other patient populations or methods is unknown, although the use of more stringent Holter criteria does not appear to influence the results.
A prospective study using a combined Holter and electrophysiological definition of drug efficacy could yield results different from those observed in the present study because many patients in the ESVEM study suppressed by only one technique would have received different therapy in a trial requiring both Holter and electrophysiological suppression. The outcome of these patients on different therapy is not known. Different results might also be expected if Holter recording were used as the primary method of determining drug efficacy (with electrophysiological evaluation at the time of the first or effective Holter trial), although this parallel protocol was not performed.
Approximately one half of the patients analyzed at the time of an effective drug trial were also included in the analysis of concordance at the time of the first drug trial (ie, first and effective trials were the same). However, since the primary analyses were different for the first drug exposure and the effective drug exposure, we do not believe this overlap to be an important limitation. Although predictors of concordance at the time of the first and the effective drug exposures may be statistically correlated, the lack of differences in outcomes between patients who met electrophysiological efficacy criteria with and without Holter suppression makes this correlation clinically unimportant. Moreover, a single analysis of predictors of concordance using the pooled population yields identical results.
Conclusions
We conclude that (1) there is a frequent
discordance in the
results of drug efficacy testing by electrophysiological study compared
with Holter monitoring; (2) a requirement for both Holter and
electrophysiological suppression reduces the number of patients who
achieve an efficacy prediction; and (3) suppression of both spontaneous
and inducible ventricular arrhythmias does not provide predictive or
prognostic benefit over suppression of either alone. Therefore, this
approach cannot be recommended at the present time.
|
Acknowledgments |
|---|
This study was supported in part by a grant (RO-1-HL34071) from the National Heart, Lung, and Blood Institute; a grant (M01-RR00064) from the National Center for Research Resources; and by Bristol-Myers Squibb Co, Knoll Pharmaceutical Co, Boehringer-Ingelheim, Parke-Davis, and Ciba-Geigy.
|
Footnotes |
|---|
1 A complete list of investigators appears in the "Appendix."
The enrollment centers and study investigators participating in the ESVEM trial are listed below. For each center, the first person listed was the principal investigator.
University of Arizona, Tucson: F.I. Marcus, A. Caruso, H.L. Faitelson, T.E. Raya, Z. Garcia, K. Gear, and M.K. Pierce; Baylor College of Medicine, Houston, Tex: C.M. Pratt, A. Boahene, A. Pacifico, C. Wyndham, and M. Francis; University of British Columbia, Vancouver: C.R. Kerr, J.A. Yeung, and S. Vorderbrugge; University of California, San Francisco: J.C. Griffin, M. Lesh, M.M. Scheinman, M. Wong, and M. Wong; University of Colorado, Denver: M.J. Reiter, D. Mann, T. Heyborne, and C. Kenny; Columbia University, New York: J.T. Bigger, Jr, J. Coromilas, F.D. Livelli, Jr, J. Reiffel, J.S. Steinberg, J. Campion, and A.M. Squatrito; University of Massachusetts, Worcester: S.K. Huang, R. Mittleman, P. Collett-Willey, and K. Rofino; Newark Beth Israel Medical Center, Newark, NJ: S. Saksena, R.B. Krol, and L. Duque; University of New Mexico, Albuquerque: R.C. Klein, C. Machell, L. Widman, C. Acosta-Miller, and G. Lomeli; Northwestern University, Chicago, Ill: R. Kehoe, T.A. Zheutlin, T. Mattioni, and C. Dunnington; University of Oklahoma, Oklahoma City: R. Lazzara, K. Beckman, K. Friday, W.M. Jackman, T. Deaton, K. Drennan, J. Foster, and S. Harris; Oregon Health Sciences University, Portland: J.H. McAnulty, J. Kron, B.D. Halperin, K. Sinner, and K. Martin; University of Pennsylvania–Presbyterian Medical Center, Philadelphia: L.N. Horowitz, C.D. Gottlieb, and C. Vrabel; University of Utah, Salt Lake City: J.W. Mason, J.L. Anderson, K.P. Anderson, R.A. Freedman, L. Karagounis, D.A. Rawling, M. Hutson, D. Mannis, and M. Roskelley.
Principal Investigator: J.W. Mason, University of Utah.
Trial Coordinating Center: University of Utah.
Data Coordinating Center (University of Arizona): T. Moon, E. Hahn, V. Hartz, A. Rico, and N. Jenrow.
Safety Monitoring Committee: R. Bressler (chair), H.L. Greene, M. Lebowitz, T. Moon, and E. Morkin.
End Points Committee: W.D. Weaver (chair), T. Bump, F. Morady, and B. Olshansky.
Received September 13, 1994; accepted November 26, 1994.
|
References |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
-
Winkle RA, Mead RH, Ruder MA, Gaudiani VA, Smith NA, Buch
WS, Schmidt P, Shipman T. Long-term outcome with the automatic
implantable cardioverter-defibrillator. J Am Coll Cardiol. 1989;13:1353-1361. [Abstract]
-
Graboys TB, Lown B, Podrid PJ, DeSilva R. Long-term survival
of patients with malignant ventricular arrhythmia treated with
antiarrhythmic drugs. Am J Cardiol. 1982;50:437-443. [Medline]
[Order article via Infotrieve]
-
Swerdlow CD, Winkle RA, Mason JW. Determinants of survival in
patients with ventricular tachyarrhythmias. N Engl J Med. 1983;308:1436-1442. [Abstract]
-
Mitchell LB, Duff HJ, Manyari DE, Wise DG. A randomized
clinical trial of the noninvasive and invasive approaches to drug
therapy of ventricular tachycardia. N Engl J Med. 1987;317:1681-1687. [Abstract]
-
Ezri MD, Huang SK, Denes P. The role of Holter monitoring in
patients with recurrent sustained ventricular tachycardia: an
electrophysiologic correlation. Am Heart J. 1984;108:1229-1236. [Medline]
[Order article via Infotrieve]
-
Platia EV, Reid PR. Comparison of programmed electrical
stimulation and ambulatory electrocardiographic (Holter) monitoring in
the management of ventricular tachycardia and ventricular fibrillation.
J Am Coll Cardiol. 1984;4:493-500. [Abstract]
-
Mason JW, for the Electrophysiologic Study Versus
Electrocardiographic Monitoring Investigators. A comparison of
electrophysiologic testing with Holter monitoring to predict
antiarrhythmic-drug efficacy for ventricular tachyarrhythmias.
N Engl J Med. 1993;329:445-451.
[Abstract/Free Full Text]
-
The ESVEM Investigators. The ESVEM trial: electrophysiologic
study versus electrocardiographic monitoring for selection of
antiarrhythmic therapy of ventricular tachyarrhythmias.
Circulation. 1989;79:1354-1360.
[Abstract/Free Full Text]
-
McNemar Q. Note on the sampling error of the difference
between correlated proportions or percentages.
Psychometrika. 1947;12:153-157.
-
Walker SH, Duncan DB. Estimation of the probability of an
event as a function of several independent variables.
Biometrika. 1967; 54:167-179.
-
Kaplan EL, Meier P. Nonparametric estimation from incomplete
observations. J Am Stat Assoc. 1958;53:457-481.
-
Cox DR. Regression models and life-tables. J R Stat Soc
(B). 1972;34:187-220.
-
Goldman L, Hashimoto B, Cook EF, Loscalzo A. Comparative
reproducibility and validity of systems for assessing cardiovascular
functional class: advantages of a new specific activity scale.
Circulation. 1981;64:1227-1234.
[Abstract/Free Full Text]
-
SAS/STAT, Release 6.04. Cary, NC: SAS Institute;
1990.
-
Greenspan AM. Determinants of antiarrhythmic drug efficacy for
ventricular tachyarrhythmias using ambulatory monitoring and
electrophysiological techniques. Circulation. 1993;87:643-645.
[Free Full Text]
-
Kim SG, Seiden SW, Matos JA, Waspe LE, Fisher JD. Discordance
between ambulatory monitoring and programmed stimulation in assessing
efficacy of class IA antiarrhythmic agents in patients with ventricular
tachycardia. J Am Coll Cardiol. 1985;6:539-544. [Abstract]
-
Herling IM, Horowitz LN, Josephson ME. Ventricular ectopic
activity after medical and surgical treatment for recurrent sustained
ventricular tachycardia. Am J Cardiol. 1980;45:633-639. [Medline]
[Order article via Infotrieve]
-
Kim SG, Seiden SW, Matos JA, Waspe LE, Fisher JD. Discordance
between ambulatory monitoring and programmed stimulation in assessing
efficacy of mexiletine in patients with ventricular tachycardia.
Am Heart J. 1986;112:14-19. [Medline]
[Order article via Infotrieve]
-
Kim SG, Felder SD, Figura I, Johnston DR, Waspe LE, Fisher JD.
Comparison of programmed stimulation and Holter monitoring for
predicting long-term efficacy and inefficacy of amiodarone used
alone or in combination with a class 1A antiarrhythmic agent in
patients with ventricular tachyarrhythmia. J Am Coll
Cardiol. 1987;9:398-404. [Abstract]
-
Nademanee K, Hendrickson J, Kannan R, Singh BN. 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;103:950-959. [Medline]
[Order article via Infotrieve]
-
Ward DE, Camm AJ. Dangerous ventricular arrhythmias: can we
predict drug efficacy? N Engl J Med. 1993;329:498-499.
[Free Full Text]
-
Kim SG. The management of patients with life-threatening
ventricular tachyarrhythmias: programmed stimulation or Holter
monitoring (either or both)? Circulation. 1987;76:1-5.
[Free Full Text]
-
Mason JW, for the ESVEM Investigators. A comparison of seven
antiarrhythmic drugs in patients with ventricular tachyarrhythmias.
N Engl J Med. 1993;329:452-458.
[Abstract/Free Full Text]
This article has been cited by other articles:
 |
|
 |
|
  M. P. Anstadt and J. E. Lowe Cardiopulmonary Resuscitation Card. Surg. Adult, January 1, 2003; 2(2003): 471 - 494. [Full Text]
|
|
|
|
 |
|
 S Brili, C Aggeli, K Gatzoulis, A Tzonou, C Hatzos, C Pitsavos, C Stefanadis, and P Toutouzas Echocardiographic and signal averaged ECG indices associated with non-sustained ventricular tachycardia after repair of tetralogy of Fallot Heart, January 1, 2001; 85(1): 57 - 60. [Abstract] [Full Text]
|
|
|
|
 |
|
 F. E. Marchlinski Predicting Arrhythmic Death : A Plea for Standardized Reporting Techniques and Data Based on Continuous Electrocardiographic Monitoring Circulation, September 16, 1997; 96(6): 1713 - 1716. [Full Text]
|
|
|
|
|
|
L. S. Gettes ESVEM and the Hazards of Clinical Trials Circulation, April 1, 1995; 91(7): 1908 - 1909. [Full Text]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||