Correspondence
Electrophysiologically Guided Antiarrhythmic Therapy versus Beta-Blocker Therapy in Patients with Ventricular Tachyarrhythmias
N Engl J Med 1993; 328:357-358February 4, 1993
- Article
To the Editor:
In their study comparing the outcomes of electrophysiologically guided antiarrhythmic therapy with those of empirical beta-blocker therapy in patients presenting with sustained ventricular arrhythmias, Steinbeck et al. (Oct. 1 issue)1 fail to take into account two important confounding variables. First, their study enrolled patients with coronary artery disease, cardiomyopathy, and other structural heart disease, without attempting to discern differences in outcome among these various groups. It has been repeatedly demonstrated that patients with cardiomyopathy and ventricular arrhythmias differ markedly from patients with coronary artery disease in their underlying substrate,2 response to serial electrophysiologic testing,3 and outcome3. Although the various underlying causes appeared to be equally distributed among the three study groups, the differences between the outcomes in patients with cardiomyopathy and the outcomes in patients with coronary disease could have skewed the outcomes reported for each group as a whole.
Second, Steinbeck et al. combined patients who presented with sustained ventricular tachycardia and those who presented with ventricular fibrillation, and disregarded important differences between these two groups4. These disparate types of patients were not equally distributed among the three study groups; patients with ventricular fibrillation were proportionately overrepresented in the “arrhythmia noninducible, metoprolol” group in Table 1 of the article. It is a serious methodologic flaw to treat patients with ventricular tachycardia and patients with ventricular fibrillation as though they were a single, homogeneous group.
It is evident that if the authors broke down their results among these heterogeneous categories of patients, their reported numbers might be too small to allow a meaningful analysis. Nevertheless, future studies should carefully take into account the important differences among these various groups.
4 ReferencesPaul T. Vaitkus, M.D.
Mark A. Capeless, M.D.
University of Vermont, Burlington, VT 054051
Steinbeck G ,Andresen D ,Bach P , et al. A comparison of electrophysiologically guided antiarrhythmic drug therapy with beta-blocker therapy in patients with symptomatic, sustained ventricular tachyarrhythmias. N Engl J Med 1992;327:987-992
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Cassidy DM ,Vassalo JA ,Miller JM , et al. Endocardial catheter mapping in patients in sinus rhythm: relationship to underlying heart disease and ventricular arrhythmias. Circulation 1986;73:645-652
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Poll DS ,Marchlinski FE ,Buxton AE ,Doherty JU ,Waxman HL ,Josephson ME . Sustained ventricular tachycardia in patients with idiopathic dilated cardiomyopathy: electrophysiologic testing and lack of response to antiarrhythmic drug therapy. Circulation 1984;70:451-456
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Vaitkus PT ,Kindwall KE ,Marchlinski FE ,Miller JM ,Buxton AE ,Josephson ME . Differences in electrophysiological substrate in patients with coronary artery disease and cardiac arrest or ventricular tachycardia: insights from endocardial mapping and signal-averaged electrocardiography. Circulation 1991;84:672-678
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To the Editor:
Steinbeck et al. used an intention-to-treat analysis to conclude that “electrophysiologically guided antiarrhythmic drug therapy did not improve the overall outcome of patients with sustained ventricular tachyarrhythmias,” as compared with empirical metoprolol therapy. We disagree with this approach, which does not differentiate between patients whose inducible arrhythmias were suppressed by antiarrhythmic drugs and patients for whom no such drug could be found. This method ignores the principal rationale for serial electrophysiologic testing and negates the value and purpose of the procedure.
Thus, an alternative conclusion can be drawn when the results in patients undergoing electrophysiologically guided therapy are compared with those in patients receiving empirical metoprolol treatment. The authors' data show that recurrent arrhythmia or sudden death occurred in 21 percent of the patients treated with a drug that suppressed inducibility and in 52 percent of the patients with inducible arrhythmias empirically treated with metoprolol. The Kaplan-Meier curves reveal that at 48 months of follow-up, survival without sudden death or recurrent arrhythmia was 78 percent in the former group and 42 percent in the latter. The outcomes in these two groups were therefore markedly different.
The study showed a significantly better outcome in patients undergoing serial drug testing for whom a drug could be identified that suppressed inducibility, as compared with patients whose arrhythmias remained inducible. This has been demonstrated in previous reports1-4.
The authors' decision regarding which drug to use in the long-term treatment of patients whose arrhythmias remained inducible after serial drug testing was based on changes in the mode of induction, the cycle length of the arrhythmia, and the symptoms during the arrhythmia. Many would dispute whether these are valid end points. An alternative approach would be to offer an implantable cardioverter-defibrillator to most patients with inducible arrhythmias after serial drug testing, because of the known high rate of recurrence in this group4.
We agree with the authors that it is unknown whether serial electrophysiologic testing of drugs in patients with sustained ventricular arrhythmias merely stratifies them into those with high probabilities of recurrence and those with low probabilities, or identifies a drug that actually prevents recurrences. Regardless, the procedure remains useful, since it identifies patients who require alternatives to therapy with antiarrhythmic drugs.
4 ReferencesMarshall S. Stanton, M.D.
Bernard I. Gersh, M.D.
Stephen C. Hammill, M.D.
Mayo Clinic, Rochester, MN 559051
Mason JW ,Winkle RA . Electrode-catheter arrhythmia induction in the selection and assessment of antiarrhythmic drug therapy for recurrent ventricular tachycardia. Circulation 1978;58:971-985
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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;58:986-997
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Wilber DJ ,Garan H ,Finkelstein D , et al. Out-of-hospital cardiac arrest: use of electrophysiologic testing in the prediction of long-term outcome. N Engl J Med 1988;318:19-24
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Waller TJ ,Kay HR ,Spielman SR ,Kutalek SP ,Greenspan AM ,Horowitz LN . Reduction in sudden death and total mortality by antiarrhythmic therapy evaluated by electrophysiologic drug testing: criteria of efficacy in patients with sustained ventricular tachyarrhythmia. J Am Coll Cardiol 1987;10:83-89
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Author/Editor Response
The authors reply:
To the Editor: Drs. Vaitkus and Capeless point out the heterogeneity of the cardiac diseases and ventricular arrhythmias in our study population. When we planned our study in 1984, major retrospective studies of serial drug testing1,2 (and, more recently, a prospective multicenter trial3) included patients with different types of cardiac disease and ventricular arrhythmias; so did we. Coronary artery disease, dilated cardiomyopathy, sustained ventricular tachycardia, and ventricular fibrillation were almost equally represented in the two randomized groups of patients in our study. Although the numbers of patients become small, the outcomes analyzed in these four subgroups with inducible arrhythmia do not appear to differ from the overall results in both treatment groups. Nevertheless, we concur with the opinion that future trials should take into account possible differences between these subgroups.
Stanton et al. address two issues regarding serial electrophysiologic drug testing: its potential to improve outcome and its role in clinical decision making. To assess the outcome of guided drug therapy, our study protocol specified that all patients randomized would be analyzed. In 1985, few electrophysiologists expected that empirical beta-blocker therapy would turn out to be so effective, as compared with therapy guided by electrophysiologic testing.
Stanton et al. propose that we compare only a favored subgroup of patients -- those in whom inducible arrhythmias could be suppressed -- with patients given beta-blockers (and that we ignore the patients who continued to have inducible arrhythmias). In our opinion, this is not correct. Instead, a valid attempt to demonstrate a better outcome would be to monitor spontaneous recurrences of the arrhythmia in the favored subgroup, with the patients not receiving long-term treatment with the drug that suppressed the inducibility of the arrhythmia. Such an approach would answer the important question of whether long-term continuation of drug treatment is essential for a good outcome (since the drug prevents the recurrence of the arrhythmia), or whether it is not essential (since suppression of inducibility identifies patients who are a priori at low risk). Such a study is under way in Germany, with an implantable defibrillator used as a backup.
Although the ultimate role of antiarrhythmic drugs remains unclear at present, our findings strongly support the view expressed by Stanton et al. : the results of electrophysiologic testing can be taken as a useful guide to selecting among the various treatments available for patients with life-threatening, sustained ventricular tachyarrhythmias.
3 ReferencesGerhard Steinbeck, M.D.
Medical Hospital I, University of Munich, 8000 Munich 70, GermanyDietrich Andresen, M.D.
Free University of Berlin, 1000 Berlin 45, Germany1
Horowitz LN ,Spielman SR ,Greenspan AM ,Josephson ME . Role of programmed stimulation in assessing vulnerability to ventricular arrhythmias. Am Heart J 1982;103:604-610
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Swerdlow CD ,Winkle RA ,Mason JW . Determinants of survival in patients with ventricular tachyarrhythmias. N Engl J Med 1983;308:1436-1442
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The ESVEM Investigators
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