VENTRICULAR ARRHYTHMIAS, ELECTROPHYSIOLOGIC STUDIES, AND DEVICES

CARDIOVASCULAR DISEASE IN THE ELDERLY

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VENTRICULAR ARRHYTHMIAS, ELECTROPHYSIOLOGIC STUDIES, AND DEVICES Anwer Dhala, MD, Jasbir Sra, MD, Zalmen Blanck, MD, Sanjay Deshpande, MD, Mohammad R. Jazayeri, MD, and Masood Akhtar, MD

In the elderly, pathologic changes involving the cardiovascular system frequently reflect prolonged exposure to various disease processes, such as atherosclerotic or hypertensive heart disease. Because of this, cardiac dysfunction and myocardial hypertrophy, the typical substrate for ventricular tachyarrhythmias, is not unusual.30The prevalence of ambient ventricular arrhythmias is known to increase with aging.l0 Sustained ventricular tachycardia and ventricular fibrillation (VT/ VF) is also not infrequent, although its incidence in the elderly is rarely reported. This article discusses treatment of sustained VT/ VF followed by management of nonsustained VT and primary prevention of sudden death. TREATMENT OF SUSTAINED VENTRICULAR TACHYCARDIA The frequency of the different causes of sustained VT/VF is age dependent with idiopathic, congenital heart diseases being common in early adulthood. Subsequently, atherosclerotic coronary artery disease accounts for more than 80% of all cases, and in the elderly, in whom the prevalence of coronary artery disease approaches 6O%, this is by far

the most common substrate for VT/VF.15* 22 Nevertheless, hypertension, valvular heart disease, and dilated cardiomyopathy are occasionally responsible. The appropriate management of VT/VF at any age should include determining the cause and extent of the underlying heart disease and identifying precipitating causes. This process usually involves right and left heart catheterization supplemented by two-dimensional echocardiography, radionuclide angiography, and stress testing. After these tests, the electrical substrate is evaluated by means of cardiac electrophysiologic testing (Table 1).

Triggers for Ventricular Tachycardia and Ventricular Fibrillation Because VT/VF is an episodic event, it is likely that some type of trigger is required to interact with the underlying arrhythmic substrate to initiate it. Various potential triggers have been implicated, including transient ischemia and reperfusion, hemodynamic dysfunction, acid-base and electrolyte abnormalities, proarrhythmic drugs, and sympathovagal imbalance. Obviously, identifying

From the Department of Medicine, University of Wisconsin Medical School-Milwaukee Clinical Campus, St. Luke's and Sinai Samaritan Medical Centers, Milwaukee Wisconsin

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Table 1. EVALUATION OF PATIENTS WITH SUSTAINED VENTRICULAR TACHRCARDIA AND VENTRICULAR FIBRILLATION Characterize type and extent of heart disease Identify factors that precipitated the transient electrophysiologic instability Define the electrophysiologic substrate by electrophysiologic testing

and avoiding these triggers could potentially abort future episodes of VT/VF. Because advanced coronary artery disease is the most common setting in which VT/VF is seen, there is a lively ongoing debate in the literature regarding the role of ischemia in the causation of VT/VF. Acute myocardial infarction is seen only in about 20% of patients presenting with sudden cardiac death. The role of transient acute ischemia, however, is more difficult to ascertain. Supporting an ischemic cause for VT/VF are autopsy studies that show active coronary thrombi in patients dying suddenly and significant freedom from sudden cardiac death during follow-up of patients undergoing coronary artery bypass grafting (CABG).7,l 2 Some autopsy studies have not found similar res~lts,2~ and the authors have reported a high incidence of appropriate shocks in patients who underwent concomitant CABG and implantable cardioverter defibrillator (ICD) implants, suggesting that CABG alone is insufficient treatment in this subgroup, especially when left ventricular dysfunction is present.25An ischemic trigger is most apparent when patients present with polymorphic VT/VF and have critical coronary stenosis and normal left ventricular function without significant myocardial scarring. In such patients, myocardial revascularization alone appears to be sufficient.lh Other precipitating factors that must be sought are electrolyte abnormalities and proarrhythmic effects of medications, especially antiarrhythmic agents. The morphology of the observed ventricular tachyarrhythmia may help determine whether a trigger can be identified. Monomorphic VT generally implies that a fixed anatomic substrate is present. In such cases, subtle alterations of the electrophysiologic milieu may be enough to precipitate tachycardia, making identification of these triggers difficult. Triggers are more often identified when the VT is polymorphic. In this situation, the baseline QT interval may provide useful clues as to the cause of the VT. Prolongation of

ECG, echocardiograpy, stress testing, cardiac catheterization, radionuclide angiography Ischemia, electrolyte imbalance, proarrhythmia drugs Confirm diagnosis of ventricular tachycardia Use to guide subsequent therapy

the QT interval may occur from a variety of different causes (most commonly antiarrhythmic agents and hypokalemia) and can provoke a type of polymorphic VT called torsades de pointes. In the absence of QT prolongation, polymorphic VT is typically precipitated by ischemia, although this type of arrhythmia may be encountered without apparent triggers as well. In the authors’ experience, precipitating factors are seen in less than a third of patients with recurrent VT/VERIn the subsequent discussion, it is assumed that VT/VF occurs in the absence of any preventable or correctable cause. Role of Electrophysiologic Testing

Traditionally, electrophysiologic testing has played a prominent role in the management of patients with or at risk for VT/VF. Programmed stimulation has been shown to induce tachycardias similar to the index tachycardia3I and therefore can be used to confirm the mechanism of a wide-complex tachycardia (supraventricular or ventricular). Additionally, if VT can be repeatedly induced, suppression of the tachycardia with an antiarrhythmic can be used to predict efficacy of that agent.3*Electrophysiologic testing is also a prerequisite when catheter ablation is being contemplated. Ablative therapy is generally considered when only a single or limited number of hemodynamically stable ventricular tachycardias are induced. Electrophysiologic testing also appears to be a good method of assessing risk for subsequent VT/VF in patients with nonsustained VT and coronary artery disease but not other types of heart disease.33 The safety of electrophysiologic testing has been well documented even in the presence of severe left ventricular dysf~nction.~ Special considerations in performing such studies in the elderly include sensitivity to sedative agents and difficulty in manipulating catheters because of tortuosity of the blood vessels and an increased propensity to cardiac perforation.

VENTRICULAR ARRHYTHMIAS, ELECTROPHYSIOLOGIC STUDIES, AND DEVICES

Therefore, particular attention needs to be given to hemodynamic and respiratory monitoring. When significant tortuosity of the vessels is encountered, use of longer vascular sheaths is helpful. Because a typical electrophysiologic study takes 45 to 60 minutes to perform, arthritic problems in the elderly may be aggravated, and special care must be taken in positioning the patient. For example, plating a prop under the knees may relieve back strain by preventing hyperextension of the low back. By improving patient comfort, these relatively simple measures reduce the need for analgesics and sedation.

Treatment of Ventricular Tachycardia and Ventricular Fibrillation VT/VF can be treated by attempting to ablate the arrhythmic focus either percutaneously or surgically, suppressing VT/VF with antiarrhythmic agents, or by promptly treating an episode once it occurs by the ICD. Choice of which therapeutic modality to use depends, in large part, on the clinical circumstances in which VT/VF is seen and the presence of comorbid conditions. The clinical presentation of ventricular tachyarrhythmias may vary from a minimal perturbation of the patient’s hemodynamic status to a catastrophic collapse leading to death within a few minutes. Several factors are responsible for determining the hemodynamic response during VT, the most important of which are the ventricular rate and underlying left ventricular function. It must also be realized that many patients with VT/VF have the substrate for multiple tachycardia circuits, and therefore the rate and morphology of subsequent episodes of VT may not be predictable on the basis of the clinical presentation of the index event. Ablative Therapy

Sustained VT is usually caused by a reentrant mechanism that occurs in areas of viable myocardium surrounded by scar tissue. Identification and removal of these areas could potentially result in a cure of the VT. Multiple recordings during VT obtained from the endocardial and epicardial surfaces aided by computer analysis of the activation time sequences have been used successfully to identify the VT circuits and resect them surgically with good long-term results. In most reported series,6 however, the surgical mortality ex-

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ceeds lo%, and the authors generally reserve this procedure for patients with monomorphic VT with a well-defined scar and otherwise preserved left ventricular function undergoing concomitant CABG. Percutaneous procedures have been developed to map and ablate these tachycardias.28aFaster and more accurate acquisition of data permits three-dimensional reconstruction of areas of slow and abnormal conduction during sinus rhythm as well as endocardia1 activation sequences during tachycardia. Rapid acquisition of data may also permit mapping of less stable tachycardias. Ablative energy delivery systems are also rapidly evolving. Despite this, many patients have unmappable tachycardias (polymorphic ventricular tachycardia, ventricular fibrillation) or epicardial or multiple tachycardia circuits. Therefore at least for the present, catheter ablation is unlikely to play a primary role in the treatment of ventricular tachyarrhythmias, especially in the presence of hemodynamically unstable rhythms. An exception may be a type of rapid hemodynamically unstable VT called bundle-branch reentrant tachycardia. In this tachycardia, the right and left bundle branches with the intervening septa1 myocardium form the reentrant circuit, and ablation of either of the bundles results in a cure.3 In the authors’ center, other than for bundle-branch reentrant tachycardia, catheter ablative therapy is reserved for patients with ICDs and repeated shocks for VT despite maximal tolerated pharmacologic therapy. Pharmacologic Therapy

A heterogeneous group of antiarrhythmic agents with variable modes of action have been approved for treatment of ventricular tachyarrhythmias. A coherent classification of these agents is difficult, but the most accepted is that developed by Vaughan Williams and is based on the presumed action of the drug in blocking a specific channel or current. Among several deficiencies, this classification does not address the differences in the pharmacokinetic and pharmacodynamic properties between these agents, an issue that is especially important in view of the narrow toxic-to-therapeutic ratio of many of these drugs.28In general, adverse effects common to many antiarrhythmics are worsening of left ventricular dysfunction and pr~arrhythmia.~~ These adverse effects are especially likely to occur when there is preexisting left ventricu-

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lar dysfunction. The proarrhythmic potential of these drugs may account at least in some measure for the generally disappointing results obtained with these agents. In fact, in most primary prevention trials, antiarrhythmic therapy with the exception of P-blockers fared worse than p l a ~ e b o . ~ At the present time, antiarrhythmics other than P-blockers should not be used in patients perceived to be at risk who have not had sustained ventricular arrhythmiasMEven in this latter group of patients with sustained ventricular tachyarrhythmias, antiarrhythmic drug therapy is associated with a high recurrence rate of nonfatal and fatal arrhythmias. For example, in the Electrophysiologic Study Versus Electrocardiographic Monitoring trial, the recurrence rate was in excess of 30% at 1 year and greater than 50% at 3 years even after electrophysiologic testing or Holter monitoring predicted the drug to be effective.'' In this trial, sotalol was more effective than the other antiarrhythmic agents tested (recurrence rate was 21% at 1 year compared with 39% to 56% for class 1 antiarrhythmic agents). Amiodarone, a drug that is somewhat similar to sotalol although not used in this trial, is widely believed to be more effective and less likely to cause proarrhythmia than sotalol. Although the recurrence rates of VT/VF are lower with amiodarone when compared with class 1 antiarrhythmic agents, the sudden death rates remain unacceptably high at 9% to 31% with its empiric use in this patient population.", l3 The results of a randomized clinical trial comparing antiarrhythmic drugs to defibrillators (Antiarrhythmics Versus Implantable Defibrillator [AVID] study) is finally available23and discussed in the following section. Implantable Cardioverter Defibrillator

Since its inception in the early 1980s, ICD therapy has undergone rapid technologic advances.*" Current-generation devices deliver tiered therapy with programmable bradycardia pacing rates, antitachycardia pacing, cardioversion, and defibrillation depending on the response of the tachyarrhythmias to termination by antitachycardia pacing or lowenergy cardioversion.' Ongoing refinements include smaller size generators, better telemetry and diagnostic functions, and dual-chamber pacing. Dual-chamber pacing allows incorporation of atrial sensing into detection algorithms, thus improving discrimination between su-

praventricular tachycardias and VT. Additionally, current-generation devices are small enough that implantation techniques are similar to that used for pacemakers and have practically eliminated the operative risk associated with thoracotomy required by the older devices. Until recently, studies assessing efficacy of ICD therapy were either single-center or multicenter outcome studies without randomization to alternate therapies and thus could not prove the superiority of ICD therapy over the other treatment modalities.*' Nonetheless, several lessons have been learned from these trials. (1) About 50% of patients receive a shock in the first 2 to 3 years. (2) ICD provides impressive freedom from sudden-presumably arrhythmic-death. (3) Non-sudden cardiac mortality from progressive cardiac dysfunction approaches 40% in 3 years when the left ventricular ejection fraction is less than 30%. (4) Appropriate shocks tend to occur in a subgroup of patients who have more severe left ventricular dysfunction and a higher non-sudden cardiac death rate. Because of some of these issues, the benefit of reducing total cardiac mortality has been que~ti0ned.l~ The ICD has been shown to be superior to antiarrhythmic agents in randomized controlled trials. In the AVID study, patients surviving life-threatening ventricular arrhythmias were assigned to either antiarrhythmic drugs (amiodarone or sotalol) or the ICD. More than 1000 patients with a mean age of 65 k 10 years were enrolled. Over a mean of 18 months, 80 deaths (16%) were noted in the ICD group compared with 122 deaths (24%) in patients treated with antiarrhythmics. The relative reduction in mortality at 1, 2, and 3 years with the ICD was 39 k 20%, 27 k 21%, and 31 k 21%. Multivariate analysis showed that the beneficial effect of ICD persisted after adjustment for other factors, including age. The average unadjusted length of additional life associated with the ICD was relatively modest at 2.7 months at 3 years in this study. Subsequent to this study, two other randomized trials comparing ICD with antiarrhythmic therapy have been completed, and unpublished results confirm the findings of the AVID trial. From the perspective of this article, it is unlikely that a sufficient number of elderly patients were included in these studies to draw conclusions that ICDs are equally beneficial in the elderly. As mentioned previously, elimination of arrhythmic mortality may have only a modest

VENTRICULAR ARRHYTHMIAS, ELECTROPHYSIOLOGIC STUDIES, AND DEVICES

effect in reducing overall mortality if a patient population at high risk for non-sudden cardiac death is chosen. Advanced age has an adverse influence on the outcome of many cardiovascular conditions. In a retrospective analysis of the authors’ ICD the outcome of 74 patients aged 75 years and older was compared with the remaining 695. In a multivariate analysis age, 275, New York Heart Association class 3, left ventricular ejection fraction less than 30%, and prior appropriate shock were predictors of mortality during follow-up. Of these, age 75 years or older was the most powerful predictor of an adverse outcome (odds ratio of 3.56; confidence interval, 2.28 to 5.54), primarily from nonsudden cardiac death. The percentage of young and elderly who received appropriate shocks in this study were similar (37%versus 38%) suggesting that the elderly had a similar frequency of arrhythmic events. Additionally, similar to their younger cohorts, sudden cardiac death incidence was low, implying that the objective of ICD therapy was achieved in the elderly. Therefore in the authors’ study, although ICD therapy provided effective treatment of VT/VF, its benefit in prolonging life was attenuated because of the high incidence of non-sudden cardiac and noncardiac death. The authors’ findings caution against the extrapolation of ICD outcome data from studies with predominantly younger patients to the elderly. Nonetheless, in the absence of other effective therapy, ICD therapy is likely to be the mainstay for the treatment of VT/ VF in the near future. The challenge to the treating physician is to identify the subgroup of patients who are at high risk for arrhythmic death but at low risk for non-sudden cardiac and noncardiac death. An approach to management of ventricular arrhythmias based on the aforementioned considerations is summarized in Figure 1. Prophylactic Treatment of Ventricular Tachycardia and Ventricular Fibrillation

Because of the poor survival of patients who experience an episode of hypotensive VT/VF, only identification and treatment of patients before sudden cardiac death is likely to have a significant positive impact on outcome. Primary prevention trials have used antiarrhythmic therapy as well as ICDs. pblockers reduce the incidence of both sudden

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cardiac death and non-sudden cardiac death. This benefit, although modest (approximately 20% reduction in mortality), has been replicated in several The class 1 antiarrhythmic agents increase mortality and should not be used. The results of two large amiodarone trials in the postinfarction population have been reported. Although arrhythmic mortality was reduced significantly, no impact on overall mortality could be l4 demon~trated.~, The current focus of primary prevention trials is the prophylactic use of ICDs. The results of two of several trials in progress are available. In the Multicenter Automatic Defibrillator Implantation Trial (MADIT), a group of patients known to be at particularly high risk for VT/VF (coronary artery disease and left ventricular dysfunction [ejection fraction ?35%], nonsustained VT, and inducible sustained VT not suppressed by procainamide) underwent ICD implantation or conventional antiarrhythmic therapy.*I A statistically significant survival benefit of 37% was seen in the ICD-treated group. Prophylactic ICDs in a different high-risk population (patients with left ventricular dysfunction and positive signal-averaged electrocardiogram undergoing CABG) were not shown to be beneficial.2 A clearer picture on the use of prophylactic use of ICDs is likely to emerge in the near future. Extrapolation of these findings to the elderly must again be made with caution for the reasons mentioned earlier. COST-EFFECTIVENESS OF IMPLANTABLE CARDIOVERTER DEFIBRILLATOR THERAPY

The current generation of ICDs do not require thoracotomy, typically require placement of a single endocardia1 lead, can be implanted in the electrophysiology laboratory, and have a postprocedure recovery time of less than 24 hours. Although this therapy has reduced costs, the initial hospitalization costs remain between $40,000 to $50,000, a substantial portion of which represents the cost of the device. Long-term costs include device follow-up, generator changes, and concomitant drug therapy. The alternate treatment modality for ventricular tachyarrhythmias, serial antiarrhythmic drug testing, requires prolonged hospitalization and multiple electrophysiologic tests and may, in fact, be more

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No VT induced

Clinical VT induced Hernodynamically stable VT

Ernpiric arniodarone

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Recurrence

Hernodynamically unstable VT

LV dysfunction

LV function normal

Critical CAD

co

Myocardial revascularization

ICD

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Change AA Catheter ablation ICD

A

1

NO

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I Inducible VT

apparent trigger

Electrophysiologic study

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No inducible VT

Bundle branch reentrant VT

ICD

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Figure 1. A, Treatment of VTNF in CAD. B, Treatment of VTNF without CAD.

expensive. Cost-effectiveness analysis compares incremental cost relative to incremental benefit. Such analysis reveals that ICD therapy is less expensive when compared with several other well-accepted medical interventions.’ CONCLUSIONS

Current studies favor the use of I C D ~in patients with VT/VF. Although the benefit of ICD therapy in prolonging life in the elderly is attenuated because of other competing causes of death, other therapies, such as surgical or catheter ablation and antiarrhythmic therapy, are even less effective.In the primary prevention of VT/VF, P-blockers demonstrate

a modest benefit. Mortality benefit from other antiarrhythmic agents is uncertain. The role of prophylactic ICD implantation in the elderly has significant social and economic implications and needs further clarification.

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VENTRICULAR ARRHYTHMIAS, ELECTROPHYSIOLOGIC STUDIES, AND DEVICES tive experience in 48 patients. J Cardiovasc Electrophysiol 4:253-262, 1993 4. Bourke J, Richards D, Ross D, et al: Routine programmed electrical stimulation in survivors of acute myocadial infarction for prediction of spontaneous ventricular tachyarrhythmias during follow-up: Results, optimal stimulation protocol and cost-effective screening. J Am Coll Cardiol 18:780-788, 1991 5. Cairns JA, Connolly SJ, Roberts RS, et al: Randomized trial of outcome after myocardial infarction in patients with frequent or repetitive ventricular premature depolarizations: CAMIAT. Lancet 349:675482, 1997 6. Cox JL: Patient selection criteria and results of surgery for refractory ischemic ventricular tachycardia. Circulation 79:I-163-1-177, 1989 7. Davies MJ, Thomas A: Thrombosis and acute coronary-artery lesions in sudden cardiac ischemic death. N Engl J Med 310:1137-1140, 1984 8. Dhala A, Deshpande S, Natale A, et a1 Is "nonclinical" induced ventricular tachycardia a clinical problem? J Am Coll Cardiol 21:328A, 1993 9. Echt DS, Liebson PR, Mitchell B, et al: Mortality and morbidity in patients receiving encainide flecainide or placebo: The cardiac arrhythmia suppression trial. N Engl J Med 324:781-788, 1991 10. Fleg JL, Kennedy HL: Cardiac arrhythmias in a healthy elderly population: Detection by 24-hour ambulatory electrocardiography. Chest 81:302-307, 1982 11. Fogoros RN, Fiedler SB, Elson JJ, et al: Empiric amiodarone versus ineffective drug therapy in patients with refractory tachyarrhythmias. Pacing Clin Electrophysiol 11:1009-1017, 1988 12. Friedman M, Manwaring JH, Rosenman RH, et al: Instantaneous and sudden deaths: Clinical and pathological differentiation in coronary artery disease. JAMA 225:1319-1328, 1973 13. 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 Coll Cardiol 3:442449, 1989 14. Julian DG, Camm AJ, Frangin G, et a1 Randomized trial of effect of amiodarone on mortality in patient with left ventricular dysfunction after recent myocardial infarction: EMIAT. Lancet 349:667-674, 1997 15. Kannel WB, Vokonas P S Demographics of the prevalence, incidence, and management of coronary heart disease in the elderly and in women. Am Epidemiol 2:5-14, 1992 16. Kelly P, Ruskin JN, Vlahakes GJ, et a1 Surgical coronary revascularization in survivors of pre-hospita1 cardiac arrest: Its effect on inducible ventricular arrhythmias and long-term survival. J Am Coll Cardiol 15:267-273, 1990 17. Kim SG: Implantable defibrillator therapy: Does it really prolong life: How can we prove it? Am J Cardiol 71:1213-1218, 1993 18. Kupperman M, Luce 8, McGovern B, et al: An analysis of the cost effectiveness of the implantable defibrillator. Circulation 81:91, 1990 19. Mason JW: A comparison of electrophysiologic testing with holter monitoring to predict antiarrhyth-

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mic-drug efficacy for ventricular tachyarrhythmias. N Engl J Med 329:445451, 1993 Mirowski M, Mower MM, Staewen WS, et al: Standby automatic defibrillator. Arch Intern Med 126:158-161, 1970 Moss Arthur J, Hall J, Cannon DS, et al: Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. N Engl J Med 335:1933-1940, 1996 Myerburg RJ, Castellanos A: Cardiac arrest and sudden cardiac death. In Braunwald E (ed): Heart Disease: A Textbook of Cardiovascular Medicine. Philadelphia, WB Saunders, 1988 Myerburg RJ, Castellanos A, et al: A comparison of antiarrhythmic-drug therapy with implantable defibrillator in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med 337:15761583, 1997 Myerburg RJ, Kessler KM, Bassett AL, et al: A biological approach to sudden cardiac death: Structure, function and cause. Am J Cardiol63:1512-1516,1989 Natale A, Axtell K, Maglio C, et al: Ventricular fibrillation and polymorphic ventricular tachycardia with critical coronary artery stenosis: Does bypass surgery suffice? J Cardiovasc Electrophysiol 5:988994, 1994 Panotopoulos PT, Axtell K, Anderson AJ, et al: Efficacy of the implantable cardioverter-defibrillator in the elderly. J Am Coll Cardiol 29:556-560, 1997 Patterson E, Szabo 8, Scherlag BJ, et al: Arrhythmogenic effects of antiarrhythmic drugs. In Zipes DP, Jalife J (eds): Cardiac Electrophysiology: From Cell to Bedside, ed 2. Philadelphia, WB Saunders, 1994, p 496 Rosen MR, Strauss HC, Janse MJ: The classification of antiarrhythmic drugs. In Zipes DP, Jalife J (eds): Cardiac Electrophysiology: From Cell to Bedside, ed 2. Philadelphia, WB Saunders, 1994, p 1277 Stevenson WG, Friedman PL, Kocovic D, et al: Radiofrequency catheter ablation of ventricular tachycardia after myocardial infarction. Circulation 98~308-314, 1998 Sweeney MO, Ruskin J, et al: Mortality benefits and the implantable cardioverter-defibrillator. Circulation 89:1851-1858, 1994 Tresch DD, Platia EV, Guarnieri T, et al: Refractory symptomatic ventricular tachycardia and ventricular fibrillation in elderly patients. Am J Med 83:399404, 1987 Wellens HJ, Schuilenburg R, Durrer D: Electrical stimulation of the heart in patients with ventricular tachycardia. Circulation 46:216-226, 1972 Wilber DJ, Garan H, Finkelstein D, et al: Out-ofhospital cardiac arrest: Use of electrophysiologic testing in the prediction of long-term outcome. N Engl J Med 318:19-24, 1988 Wilber DJ, Olshansky B, Moran JF, et al: Electrophysiologic testing and nonsustained ventricular tachycardia: Use and limitation in patients with coronary artery disease and impaired ventricular function. Circulation 82:350-358, 1990 Yusuf S, Wittes J, Friedman L: Overview of results of randomized clinical trials in heart disease: I. Treatments following myocardial infarction. JAMA 260:2088-2095, 1988

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