Hospital Practice
ISSN: 2154-8331 (Print) 2377-1003 (Online) Journal homepage: http://www.tandfonline.com/loi/ihop20
Prevention of Sudden Cardiac Death Arthur J. Moss To cite this article: Arthur J. Moss (1992) Prevention of Sudden Cardiac Death, Hospital Practice, 27:11, 165-176, DOI: 10.1080/21548331.1992.11705528 To link to this article: http://dx.doi.org/10.1080/21548331.1992.11705528
Published online: 17 May 2016.
Submit your article to this journal
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ihop20 Download by: [La Trobe University]
Date: 30 May 2016, At: 20:00
Prevention of Sudden Cardiac Death
Downloaded by [La Trobe University] at 20:00 30 May 2016
ARTHuR J.
Moss
University of Rochester
Since the vast majority of these deaths are triggered by arrhythmias, the first step in prevention is to understand the risk factors for malignant rhythms. The second is to identify patients who may benefit from preventive intervention. Finally, who should get drugs, who automatic cardioverter-defibrillator implantation. The determinants of that choice remain to be elucidated.
Every day in the United States, approximately 1,000 people die of sudden cardiac arrest. Annually, the death toll is between 300,000 and 400,000. Sudden cardiac death accounts for about half of all cardiac mortality each year, and occurs at almost every age, including childhood and adolescence. In 90% to 95% of cases, the mechanism is a ventricular tachyarrhythmia that rapidly deteriorates into ventricular fibrillation and circulatory collapse. With rare exceptions, the fibrillation is malignant-that is, not spontaneously reversible. In a small number of cases, death appears to result from asystolic cardiac arrest. The heart simply stops pumping. It is generally acknowledged that heart disease is the substrate of sudden cardiac death. Clinical experience and pathologists' reports inform us that the majority of patients who experience sudden cardiac death have significant coronary artery disease. Patients with cardiomyopathy, hypertensive heart disease, mitral valve prolapse, congenital rhythm disorders such as the long Q-T syndrome and WolffParkinson-White syndrome, and surgically corrected congenital heart defects also account for sudden cardiac deaths. Despite awareness of sudden cardiac death as a significant public health problem, this disorder has been difficult to prevent-not because we lack therapy but because it is very hard to identify in advance those at risk for sudden, life-threatening arrhythmias who might benefit from therapy. The problem of risk identification is complex, as indicated by the Dr. Moss is Professor of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, N.Y.
work by Leonard Cobb, of the Seattle Heart Watch program, who reviewed over 500 patients successfully resuscitated from cardiac arrest. He found that although acute myocardial infarction was the leading risk factor for sudden cardiac death, only 20% of the patients studied had experienced an acute MI. Furthermore, although 80% to 90% had atherosclerotic coronary disease, usually involving two or more vessels, only half of these patients were aware that they had heart disease. In trying to identify patients at risk, a critical question is: What activates an underlying heart disease into a malignant arrhythmia? The triggering mechanism is presumably in the autonomic nervous system, perhaps the release of epinephrine during an acute arousal situation-or conversely, the withdrawal of vagal stimuli, which tend to stabilize the heart rhythm. Although the subject of considerable research, the exact mechanism remains to be defined. In addition to the substrate and the trigger mechanism, the presence ofmodu1atingfactors, particularly certain drugs, may enhance the potential for dangerous rhythms. The role of various drugs as modulating factors will be discussed later. About one third of sudden cardiac deaths in patients with coronary artery disease occur instantaneously-that is, less than one minute after the onset of symptoms. This finding emerged from our retrospective analysis of data in 229 post-myocardial infarction patients who died of cardiac causes during a two-year follow-up. All patients had been judged to be at a good functional level. At the time of Hospital Practice November 15. 1992
165
Downloaded by [La Trobe University] at 20:00 30 May 2016
death, 74 (32%) died instantaneously, arguably of ventricular fibrillation; 32 ( 14%) died between one minute and one hour afteronsetofsymptoms, and 123 (54%) after more than one hour (Figure 1). The high percentage of instantaneous deaths among these patients underscores the importance of prevention. Malignant arrhythmias usually occur without forewarning, but large-scale, multicenter riskstratification studies have pinpointed certain signs and symptoms as implying increased risk. Stratifying risk on the basis of three levels of diagnostic evaluation-clinical findings, results of noninvasive tests, and results of invasive electrophysiologic data -has been used to identify patients most likely to experience sudden cardiac death. The concept of risk stratification is illustrated by a Venn diagram with its three interlocking circles, each representing the data from one of the three levels of diagnostic studies. When the positive findings from the three categories overlap, a high degree of risk is indicated. The potential for malignant arrhythmia has been extensively studied in patients recovering from acute myocardial infarction, and the risk factors are relatively well defined. Among patients with known coronary artery disease and a history of myocardial infarction, clinical findings of light-headedness or syncope, an abnormal electrocardiogram, and left ventricular dysfunction with an ejection fraction ofless than 0.30 define a group at higher risk for sudden cardiac death than the general population. Patients exhibiting these clinical characteristics warrant further study with noninvasive tests, including exercise testing, 166
24-hour Holter monitoring, and, perhaps, signal-averaged ECG studies. Evidence of ventricular irritability would be an ominous finding. A strong causal relationship between ventricular ectopic beats and arrhythmic sudden death has been demonstrated in postinfarction patients. The occurrence of frequent and complex ventricular ectopic beats (more than three per hour and three or more in a row) contributes significantly to the risk. Low heart rate variability is another important risk factor. Heart rate variability is defined as the standard deviation of all normal R-R intervals in a 24hour Holter recording. Patients with low heart rate variability tend to maintain a constant, somewhat accelerated heart rate regardless of whether they are active or resting. The finding may indicate either decreased vagal tone or increased sympathetic nervous activity, either of which could predispose the heart to ventricular fibrillation. A measurement of less than 50 msec indicates low variability and correlates strongly with risk of malignant arrhythmia. In addition to the clinical findings already mentioned, patients who have repetitive extra heartbeats and evidence oflate potentials appear to be 15 to 20 times as likely to have a malignant rhythm disorder as post-MI patients who do not have these findings. In such cases, the risk is sufficient to warrant use of invasive studies. To stratify these patients further, they may undergo intracardiac electrophysiologic testing, with electrodes placed in the heart via a cardiac catheter for the purpose of stimulating ventricular tachycardia under controlled conditions. A study of 100 high-risk patients by David Wilber at Loyola University
Hospital Practice November 15. 1992
Medical Center, Maywood, Ill., showed that those with inducible arrhythmias that could not be suppressed with intravenous procainamide had a 50% actuarial incidence of cardiac arrest or sudden death within two years. Although I have used the example of coronary artery disease to show how risk stratification can be used to identify patients at greatest risk for sudden cardiac death, the concept is also applicable to patients with other types of heart disease who might benefit from preventive therapy. To summarize the results of risk stratification studies in patients with coronary artery disease, it appears that those at greatest risk for sudden cardiac death have a history of myocardial infarction, a decreased ejection fraction, low heart rate variability, and complex ventricular rhythms. Among patients with cardiomyopathy, a diagnosis of dilatedtype disease with an associated intraventricular conduction disturbance confers a high level of risk. Many of these patients have markedly impaired mechanical function and are candidates for heart transplantation. Nevertheless, one third to one half die of sudden arrhythmia, even though the basic problem is mechanical. Providing temporary salvage for such patients while they are awaiting a heart transplant is an urgent therapeutic goal. Patients with Wolff-ParkinsonWhite syndrome are born with an accessory conduction system in the heart that predisposes to reentrant supraventricular tachyarrhythmias, potential atrial fibrillation, and ventricular fibrillation. The risk factors for sudden cardiac death, which is relatively rare in these patients, include a history of syncope; episodes of both reentrant su-
Downloaded by [La Trobe University] at 20:00 30 May 2016
praventricular tachyarrhythmia and atrial fibrillation; atrial fibrillation with R-R intervals of less than 250 msec; consistent presence of delta waves, even on class I antiarrhythmic therapy such as quinidine; and evidence of multiple accessory pathways. For those who have symptoms and at least one risk factor, electrophysiologic testing is indicated to determine vulnerability to ventricular fibrillation. The long Q-T syndrome is characterized by prolongation of ventricular repolarization. The defect, which may be either congenital or acquired, predisposes to malignant ventricular arrhythmias. In the congenital form, the heart is normal except for an apparent alteration at the membrane level, probably in the ionic currents that cross cardiac myocyte membranes, resulting in delayed repolarization of the heart's electrical activity. Recurrent episodes of syncope may occur. These episodes are due to malignant ventricular tachyarrhythmias, characterized by the rapid polymorphous configuration known as torsade de pointes. The tachycardia usually ceases spontaneously, but it may degenerate into ventricular fibrillation and death. The risk factors associated with torsade or ventricular fibrillation in patients with the heritable form of the long Q-T syndrome include marked T-U wave abnormality, T-wave alternans, history of syncope or an episode of ventricular tachyarrhythmia, family history of unexplained sudden cardiac death before age 40, and congenital deafness. Mitral valve prolapse, with the click-murmur finding on auscultation and frequent ventricular ectopic beats, is fairly common in the general population. Sud-
Figure 1. Retrospective analysis of sudden cardiac death in 229 post-MI patients during a two-year period showed that 74 died within a minute of symptom onset, 10 between one and five minutes, 17 between 10 and 30 minutes, 5 between 40 and 60 minutes, and 123 after more than one hour.
den death has been reported in association with this disorder. Moreover, among patients with MVP. a high-risk subset can be identified by the presence of a combination of the following diagnostic findings: unexplained syncope; a prominent MVP murmur; female sex in the 30-to-40 age group; ST depression and Twave inversion in the inferior limb leads of the ECG, together with borderline or frank Q-T prolongation; and frequent or repetitive ventricular ectopic beats. Congenital heart defects are readily diagnosed and treated surgically, but patients are often left with a scar. It is believed that
such scars can serve as the nidus for the development of complex rhythms, and even predispose to malignant arrhythmia. The problem has only recently been recognized. In patients with underlying heart disease, some medications can trigger rhythm disorders. Use of such drugs in patients susceptible to rhythm disorders may be considered an additional risk factor. Among the drugs with recognized triggering activity are some used to treat heart disease, including some antiarrhythmic agents, the new antianginal medication bepridil, and cardiac glycosides that have been used for over two centuries.
Hospital Practice November 15. 1992
167
rhythmic agents in terms of ventricular arrhythmia suppression. However, in 1989 (two years into the planned three-year CAST study), it became evident that use of these agents was associated with increased mortality. Furthermore, the mortality among patients receiving either of the drugs was predominantly due to sudden cardiac arrest. The drugs were recategorized as proarrhythmic agents, but the mechanism of their proarrhyth-
Downloaded by [La Trobe University] at 20:00 30 May 2016
A dramatic example of adverse arrhythmic activity emerged unexpectedly from the Cardiac Arrhythmia Suppression Trial (CAST). The multicenter study, sponsored by the National Institutes of Health, was designed to test the hypothesis that suppression of ventricular ectopic beats would reduce the incidence of sudden cardiac death in post-MI patients. Two of the study drugs, encainide and flecainide, had been shown to be effective antiar-
Figure 2. When Joel Morganroth and James E. Goin analyzed data from four trials comparing quinidine with other class I antiarrhythmic agents, observed mortality associated with quinidine was higher than that associated with flecainide, mexiletine, or propafenone, and equal to that associated with tocainide.
168
Hospital Practice November 15. 1992
mic activity remains unclear. Quinidine is the oldest and still the most frequently prescribed of the traditional class I antiarrhythmics available in this country. Its safety and efficacy have never been rigorously tested, although it has long been known to have proarrhythmic activity. Evidence that quinidine may actually enhance the risk of mortality in patients being treated for arrhythmia comes from a study by Joel Morganroth and James E. Goin at the University of Pennsylvania. They performed a meta-analysis of data from four drug trials in which quinidine was compared with other class I an tiarr hythmics-flecainide, mexiletine, tocainide, or propafenone-for short-term treatment of benign or malignant ventricular arrhythmias in 1,009 patients. Observed mortality was proportionately greater among the 502 patients taking quinidine ( 12 deaths) than among 507 patients taking one of the other drugs (4 deaths) (Figure 2 l. The risk of dying while on quinidine was also significantly higher. Another drug with known proarrhythmic activity is the antianginal agent bepridil. It can produce life-threatening complex rhythms, particularly in vulnerable patients taking other heart medications. A relationship between digitalis therapy and increased mortality in survivors of myocardial infarction has been noted in a number of studies, but its significance is unclear. It has been suggested that the finding is merely an artifact. In one of our studies, we found that mortality at four months postinfarction was highest in patients treated with digitalis who had evidence of left ventricular dysfunction and (continues)
Downloaded by [La Trobe University] at 20:00 30 May 2016
SUDDEN DEATH
(continued)
complex ventricular rhythms at hospital discharge. In the study of instantaneous cardiac death mentioned previously, we found a strong association with digitalis therapy. Sixty-six of the 7 4 patients who died instantaneously were taking digitalis during the week before death, compared with 39 of 155 whose deaths were classified as noninstantaneous. Both studies were carefully controlled for confounding clinical factors. If digitalis in fact has an independent effect on mortality, our findings suggest that it enhances the risk of arrhythmia. Other drugs that may have an adverse effect on heart rhythm in susceptible patients include diuretics that alter the potassium content of the body, terfenadine (an H 1-receptor antagonist widely prescribed for allergic rhinitis), and some psychotropic agents, such as chlorpromazine and thioridazine. In emphasizing risk factors for sudden cardiac death and the need to identify patients who can benefit from preventive therapy, it should be noted that there are two therapeutic options: drugs and the automatic implantable cardioverter-defibrillator. Patient selection is extremely important in determining how effectively we use each option. Let us consider drug therapy first. In patients with symptomatic, complex ventricular arrhythmias, physiologic testing may be used to identify an antiarrhythmic drug that will suppress the induced malignant arrhythmia. ,8-Blockers stand out as a class of drugs effective in reducing the rate of both sudden and nonsudden cardiac death in high-risk patients. The classic Beta Blocker Heart Attack Trials estab-
Figure 3. In transthoracic implantation of the cardioverter-defibrillator, two sensing electrodes are placed in the ventricular myocardium, and anodal and cathodal patches are placed on the anterior right ventricle and left ventricular apex, respectively. Lead conductors are tunneled under the skin to the pulse generator, which lies in a subcutaneous pocket of the left upper abdomen.
lished that propranolol reduced mortality by approximately 25% compared with placebo. The ,8blockers are class II antiarrhythmic agents that have demonstrated long-term safety and do not appear to have any proarrhythmic activity. For patients with inducible arrhythmias that are not suppressible with class I or class II antiarrhythmics, the class III drugs amiodarone and sotalol have shown some efficacy in preventing sudden cardiac death in clinical trials. A meta-analysis of randomized trials of amiodarone suggested a 34% reduction in mortality in post-MI patients. 1\vo large-scale trials in
Europe and Canada have been organized to assess amiodarone's effect on survival in high-risk postinfarction patients. The results of these studies will be available in two or three years. The alternative to drug theraPY is the automatic implantable cardioverter-defibrillator (Figure 3). The first such device was developed by Michel Mirowski and his co-workers at Sinai Hospital of Baltimore and Intec Systems, Pittsburgh. An automatic defibrillator device was implanted in a patient who had had an out-of-hospital cardiac arrest. When the patient had another spontaneous episode several
Hospital Practice November 15. 1992
173
Downloaded by [La Trobe University] at 20:00 30 May 2016
months later, the device shocked him out of the potentially fatal rhythm and he survived. Thereport of this single case in the New England Journal of Medicine in 1980 provoked widespread interest. Over the past 12 years, the device has undergone technological improvements. For example, as both a cardioverter and a defibrillator, it now can convert tachycardia before the heart actually fibrillates, and it can terminate fibrillation within eight to 10 seconds. Currently, the only device approved by the Food and Drug Administration uses electrodes placed on the heart and therefore requires open thoracotomy for implantation. Usually, two sensing electrodes are placed in the ventricular myocardium, an anodal patch is placed on the anterior right ventricle, and the cathodal patch on the left ventricular apex. The lead conduc-
tors are tunneled under the skin to the pulse generator, which is placed in a subcutaneous pocket in the left upper abdominal wall. To date, approximately 30,000 automatic cardioverter-defibrillators have been implanted worldwide. The latest evolution in the technology is transvenous implantation of a three-lead system. 1\vo electrodes are placed endocardially via a cardiac catheter: one in the right ventricular apex and one at the junction of the superior vena cava and right atrium. The patch electrode is surgically placed in the left thoracic wall, and its lead is crossconnected with a Y connector to the right atrial lead to create a bidirectional current. The lead conductors are tunneled subcutaneously along the left thoracic wall to the pulse generator, which is placed in the abdominal wall. About 500 units have thus
Ventricular Fibrillation Detected
Figure 4. A three-lead ECG recorded events in the operation of an implantable cardioverter-defibrillator: detection of
17 4
Hospital Practice November 15. 1992
Start Charge
far been implanted via the transvenous approach. The same battery-powered pulse generator, which can deliver approximately 100 discharges, is used with both electrode systems. It can also store information, such as the number of times it has discharged, and this information can be retrieved. A recent improvement in the unit is the capacity to record the type of rhythm the patient had when it discharged. Further improvements will undoubtedly lead to smaller pulse generators with increased memory. At present, the automatic implantable cardioverter-defibrillator has been approved for the treatment of patients who have had an aborted out-of-hospital cardiac arrest and patients who have evidence oflife-threatening hypotensive ventricular tachycardia. We have already noted that patients with heart disease
End Charge
First Shock Delivery
ventricular fibrillation, initiation and completion of charging, and delivery of a shock. Sinus rhythm was restored.
Downloaded by [La Trobe University] at 20:00 30 May 2016
who have survived an episode of cardiac arrest have a 50% risk of a second, fatal event within two years. Ventricular tachycardia is not necessarily a malignant arrhythmia, but when accompanied by a drop in blood pressure, it can quickly deteriorate into ventricular fibrillation. There is no question that the device will defibrillate the heart if the patient has a fibrillatory episode (Figure 4). Efficacy is well documented in many medical centers in the United States, Canada, and Europe. Clinical studies of patients with automatic implantable cardioverter-defibrillators have typically recorded mortality of 10% at one year and about 20% at two to three years. These figures represent a dramatic reduction from the expected greater than 50% mortality at two years (Figure 5). Unfortunately, most of the studies have been retrospective, with no control group, or with historical controls. In a review of 10 retrospective studies, Stuart J. Connolly at McMaster University, Hamilton, Ont .. and Salim Yusuf at the National Heart, Lung, and Blood Institute, Bethesda, noted that there were biases in patient selection in many studies that could have led to lower-risk patients receiving automatic implantable cardioverter-defibrillator therapy. Two troubling questions left unanswered by these studies are, Have we sufficiently defined the patient population that will benefit from the device? Is it clearly beneficial compared with the best medical therapy? To date, there are no results from prospective randomized controlled studies that could provide the answers, but five such studies are planned or have been initiated. The Hamburg Cardiac Arrest Study in Germany, comparing
Figure 5. Richard N. Fogoros and co-workers found that mean cumulative survival was 97% at 12 months, 90% at 24 months, and 85% at 36 months in 119 patients who had received an implantable cardioverter-defibrillator and were followed for a mean of 21 months. In contrast, projected survival of these patients in the absence of implantation was calculated by the investigators to be 59% at 12 months, 39% at 24 months, and 31% at 36 months.
the automatic implantable cardioverter-defibrillator with antiarrhythmic drug therapy in survivors of cardiac arrest, is the first to issue interim results. With an 11-month mean followup of 139 patients randomized to receive implant treatment. amiodarone, propafenone, or metoprolol, the rate of sudden death in the cardioverter-defibrillator group was zero, in the amiodarone group, 9%, and 11% each in the groups receiving metoprolol and propafenone. Overall mortality was not significantly different between the implant patients ( 14%) and those patients on medical therapy ( 14% metoprolol. 15% amiodarone, 20% propafenone) in this short-term follow-up. The Canadian Implantable
Defibrillator Study (CIDS) will ultimately involve about 400 patients who have survived cardiac arrest, with at least 100 already entered. Patients are randomized to receive an automatic implantable cardioverter-defibrillator or to be treated with amiodarone. Another large-scale prospective study of patients who had an aborted cardiac arrest has been funded by the NHLBI. The study, which has not begun, calls for recruitment of 700 to 800 patients who will be randomized to receive either an automatic implantable cardioverter-defibrillator or conventional medical therapy. J. Thomas Bigger, Jr., of Columbia University is heading the multicenter CABG Patch Trial. a projected two- to five-year
Hospital Practice November 15, 1992
175
study of about 800 patients. This trial is enrolling patients under age 80 who are candidates for elective coronary artery bypass surgery and who have an ejection fraction of less than 0.36 and a positive signal-averaged ECG (a sensitive marker in patients at risk for lethal ventricular ar-
rhythmias). Patients are randomized at the time of surgery to receive an automatic implantable cardioverter-defibrillator as well or coronary bypass only. Morbidity and mortality with or without the cardioverterdefibrillator will be compared. The Multicenter Automatic De-
Selected Reading Moss AJ: Identification of patients at increased risk for potentially malignant arrhythmias. Cardiovasc Drugs Ther 4: 665, 1990 Moss AJ. Robinson J: Clinical features of the idiopathic long QT syndrome. Circulation 85 (suppli):I-140, 1992
Downloaded by [La Trobe University] at 20:00 30 May 2016
Wilber DJ et al: Electrophysiological testing and nonsustained ventricular tachycardia: Use and limitations in patients with coronary artery disease and impaired ventricular function. Circulation 82: 350, 1990 Waller T J et al: Reduction in sudden death total mortality by antiarrhythmic therapy evaluated by electrophysiologic drug testing: Criteria of efficacy in patients with sustained ventricular tachyarrhythmia. JAm Coll Cardiol10: 83, 1987 Furberg CD. Yusuf S: Antiarrhythmics and VPD suppression. Circulation 84:928, 1991 Echt DS et al: Mortality and morbidity in patients receiving encainide, flecainide, or placebo: The Cardiac Arrhythmia Suppression Trial. N Engl J Med 324 : 781, 1991 Morganroth J, Goin JE: Quinidine-related mortality in the short-to-medium-term treatment of ventricular arrhythmias: A meta-analysis. Circulation 84: 1977, 1991 Connolly SJ, YusufS: Evaluation of the implantable cardioverter defibrillator in survivors of cardiac arrest: The need for randomized trials (editorial). Am J Cardiol69: 959, 1992 Fogoros RN et al: Efficacy of the automatic implantable cardioverter-defibrillator in prolonging survival in patients with severe underlying cardiac disease. JAm Coll Cardiol 16: 381. 1990 Lehmann MH et al: The automatic implantable cardioverter defibrillator as antiarrhythmic treatment modality of choice for survivors of cardiac arrest unrelated to acute myocardial infarction (editorial). Am J Cardiol 62:803, 1988 Saksena S: Clinical progress in endocardial defibrillation. Clin Cardiol 12:709, 1989 Gabry MD et al: Automatic implantable cardioverter-defibrillator: Patient survival. battery longevity and shock delivery analysis. JAm Coll Cardiol 9:1349,1987 Saksena Setal: Long-term multicenter experience with a second-generation implantable pacemaker-defibrillator in patients with malignant ventricular tachyarrhythmias. JAm Coll Cardiol 19: 490, 1992 Newman D et al: Survival after implantation of the cardioverter defibrillator. Am J Cardia! 69 : 899. 1992 Tchou PJ et al: Automatic implantable cardioverter defibrillators and survival of patients with left ventricular dysfunction and malignant ventricular arrhythmias. Ann Intern Med 109:529, 1988 MAD IT Executive Committee: Multicenter Automatic Defibrillator Implantation Trial (MADIT): Design and clinical protocol. PACE Pacing Clin Electrophysiol14: 920 (part II), 1991
176
Hospital Practice November 15, 1992
fibrillator Implantation Trial (MAD IT) has been under way for over a year and has enrolled more than 60 patients. The major requirements for study entry are an episode of nonsustained ventricular tachycardia, a prior Q-wave infarction, a reduced ejection fraction, and inducible but nonsuppressible ventricular tachycardia on electrophysiologic testing. Patients with these characteristics are randomly assigned to receive either an automatic implantable cardioverter-defibrillator or conventional medical therapy. The medication prescribed is left to the patient's cardiologist. Medical therapy can also be given to patients who receive a unit. Thus, the only essential difference between the two groups should be the automatic implantable cardioverter-defibrillator. The study will be terminated at the earliest evidence that the device either is or is not effective in increasing survival. Performing randomized controlled studies in a patient population with a baseline 50% mortality risk poses tough ethical questions. It can be argued that a potentially lifesaving treatment should not be withheld from such patients. On the other hand, without controlled studies, it is impossible to substantiate that such therapy is clearly beneficial. During the 1980s, the automatic implantable cardioverterdefibrillator evolved technologically, and we gained experience with it. Certainly, it has been well documented that the device works in the setting of an acute fibrillation. Now it is time to define the population that will benefit from this new technology so that it is used appropriately and not abused. That is how we advance the science of clinical medicine.
ISSN: 2154-8331 (Print) 2377-1003 (Online) Journal homepage: http://www.tandfonline.com/loi/ihop20
Prevention of Sudden Cardiac Death Arthur J. Moss To cite this article: Arthur J. Moss (1992) Prevention of Sudden Cardiac Death, Hospital Practice, 27:11, 165-176, DOI: 10.1080/21548331.1992.11705528 To link to this article: http://dx.doi.org/10.1080/21548331.1992.11705528
Published online: 17 May 2016.
Submit your article to this journal
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ihop20 Download by: [La Trobe University]
Date: 30 May 2016, At: 20:00
Prevention of Sudden Cardiac Death
Downloaded by [La Trobe University] at 20:00 30 May 2016
ARTHuR J.
Moss
University of Rochester
Since the vast majority of these deaths are triggered by arrhythmias, the first step in prevention is to understand the risk factors for malignant rhythms. The second is to identify patients who may benefit from preventive intervention. Finally, who should get drugs, who automatic cardioverter-defibrillator implantation. The determinants of that choice remain to be elucidated.
Every day in the United States, approximately 1,000 people die of sudden cardiac arrest. Annually, the death toll is between 300,000 and 400,000. Sudden cardiac death accounts for about half of all cardiac mortality each year, and occurs at almost every age, including childhood and adolescence. In 90% to 95% of cases, the mechanism is a ventricular tachyarrhythmia that rapidly deteriorates into ventricular fibrillation and circulatory collapse. With rare exceptions, the fibrillation is malignant-that is, not spontaneously reversible. In a small number of cases, death appears to result from asystolic cardiac arrest. The heart simply stops pumping. It is generally acknowledged that heart disease is the substrate of sudden cardiac death. Clinical experience and pathologists' reports inform us that the majority of patients who experience sudden cardiac death have significant coronary artery disease. Patients with cardiomyopathy, hypertensive heart disease, mitral valve prolapse, congenital rhythm disorders such as the long Q-T syndrome and WolffParkinson-White syndrome, and surgically corrected congenital heart defects also account for sudden cardiac deaths. Despite awareness of sudden cardiac death as a significant public health problem, this disorder has been difficult to prevent-not because we lack therapy but because it is very hard to identify in advance those at risk for sudden, life-threatening arrhythmias who might benefit from therapy. The problem of risk identification is complex, as indicated by the Dr. Moss is Professor of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, N.Y.
work by Leonard Cobb, of the Seattle Heart Watch program, who reviewed over 500 patients successfully resuscitated from cardiac arrest. He found that although acute myocardial infarction was the leading risk factor for sudden cardiac death, only 20% of the patients studied had experienced an acute MI. Furthermore, although 80% to 90% had atherosclerotic coronary disease, usually involving two or more vessels, only half of these patients were aware that they had heart disease. In trying to identify patients at risk, a critical question is: What activates an underlying heart disease into a malignant arrhythmia? The triggering mechanism is presumably in the autonomic nervous system, perhaps the release of epinephrine during an acute arousal situation-or conversely, the withdrawal of vagal stimuli, which tend to stabilize the heart rhythm. Although the subject of considerable research, the exact mechanism remains to be defined. In addition to the substrate and the trigger mechanism, the presence ofmodu1atingfactors, particularly certain drugs, may enhance the potential for dangerous rhythms. The role of various drugs as modulating factors will be discussed later. About one third of sudden cardiac deaths in patients with coronary artery disease occur instantaneously-that is, less than one minute after the onset of symptoms. This finding emerged from our retrospective analysis of data in 229 post-myocardial infarction patients who died of cardiac causes during a two-year follow-up. All patients had been judged to be at a good functional level. At the time of Hospital Practice November 15. 1992
165
Downloaded by [La Trobe University] at 20:00 30 May 2016
death, 74 (32%) died instantaneously, arguably of ventricular fibrillation; 32 ( 14%) died between one minute and one hour afteronsetofsymptoms, and 123 (54%) after more than one hour (Figure 1). The high percentage of instantaneous deaths among these patients underscores the importance of prevention. Malignant arrhythmias usually occur without forewarning, but large-scale, multicenter riskstratification studies have pinpointed certain signs and symptoms as implying increased risk. Stratifying risk on the basis of three levels of diagnostic evaluation-clinical findings, results of noninvasive tests, and results of invasive electrophysiologic data -has been used to identify patients most likely to experience sudden cardiac death. The concept of risk stratification is illustrated by a Venn diagram with its three interlocking circles, each representing the data from one of the three levels of diagnostic studies. When the positive findings from the three categories overlap, a high degree of risk is indicated. The potential for malignant arrhythmia has been extensively studied in patients recovering from acute myocardial infarction, and the risk factors are relatively well defined. Among patients with known coronary artery disease and a history of myocardial infarction, clinical findings of light-headedness or syncope, an abnormal electrocardiogram, and left ventricular dysfunction with an ejection fraction ofless than 0.30 define a group at higher risk for sudden cardiac death than the general population. Patients exhibiting these clinical characteristics warrant further study with noninvasive tests, including exercise testing, 166
24-hour Holter monitoring, and, perhaps, signal-averaged ECG studies. Evidence of ventricular irritability would be an ominous finding. A strong causal relationship between ventricular ectopic beats and arrhythmic sudden death has been demonstrated in postinfarction patients. The occurrence of frequent and complex ventricular ectopic beats (more than three per hour and three or more in a row) contributes significantly to the risk. Low heart rate variability is another important risk factor. Heart rate variability is defined as the standard deviation of all normal R-R intervals in a 24hour Holter recording. Patients with low heart rate variability tend to maintain a constant, somewhat accelerated heart rate regardless of whether they are active or resting. The finding may indicate either decreased vagal tone or increased sympathetic nervous activity, either of which could predispose the heart to ventricular fibrillation. A measurement of less than 50 msec indicates low variability and correlates strongly with risk of malignant arrhythmia. In addition to the clinical findings already mentioned, patients who have repetitive extra heartbeats and evidence oflate potentials appear to be 15 to 20 times as likely to have a malignant rhythm disorder as post-MI patients who do not have these findings. In such cases, the risk is sufficient to warrant use of invasive studies. To stratify these patients further, they may undergo intracardiac electrophysiologic testing, with electrodes placed in the heart via a cardiac catheter for the purpose of stimulating ventricular tachycardia under controlled conditions. A study of 100 high-risk patients by David Wilber at Loyola University
Hospital Practice November 15. 1992
Medical Center, Maywood, Ill., showed that those with inducible arrhythmias that could not be suppressed with intravenous procainamide had a 50% actuarial incidence of cardiac arrest or sudden death within two years. Although I have used the example of coronary artery disease to show how risk stratification can be used to identify patients at greatest risk for sudden cardiac death, the concept is also applicable to patients with other types of heart disease who might benefit from preventive therapy. To summarize the results of risk stratification studies in patients with coronary artery disease, it appears that those at greatest risk for sudden cardiac death have a history of myocardial infarction, a decreased ejection fraction, low heart rate variability, and complex ventricular rhythms. Among patients with cardiomyopathy, a diagnosis of dilatedtype disease with an associated intraventricular conduction disturbance confers a high level of risk. Many of these patients have markedly impaired mechanical function and are candidates for heart transplantation. Nevertheless, one third to one half die of sudden arrhythmia, even though the basic problem is mechanical. Providing temporary salvage for such patients while they are awaiting a heart transplant is an urgent therapeutic goal. Patients with Wolff-ParkinsonWhite syndrome are born with an accessory conduction system in the heart that predisposes to reentrant supraventricular tachyarrhythmias, potential atrial fibrillation, and ventricular fibrillation. The risk factors for sudden cardiac death, which is relatively rare in these patients, include a history of syncope; episodes of both reentrant su-
Downloaded by [La Trobe University] at 20:00 30 May 2016
praventricular tachyarrhythmia and atrial fibrillation; atrial fibrillation with R-R intervals of less than 250 msec; consistent presence of delta waves, even on class I antiarrhythmic therapy such as quinidine; and evidence of multiple accessory pathways. For those who have symptoms and at least one risk factor, electrophysiologic testing is indicated to determine vulnerability to ventricular fibrillation. The long Q-T syndrome is characterized by prolongation of ventricular repolarization. The defect, which may be either congenital or acquired, predisposes to malignant ventricular arrhythmias. In the congenital form, the heart is normal except for an apparent alteration at the membrane level, probably in the ionic currents that cross cardiac myocyte membranes, resulting in delayed repolarization of the heart's electrical activity. Recurrent episodes of syncope may occur. These episodes are due to malignant ventricular tachyarrhythmias, characterized by the rapid polymorphous configuration known as torsade de pointes. The tachycardia usually ceases spontaneously, but it may degenerate into ventricular fibrillation and death. The risk factors associated with torsade or ventricular fibrillation in patients with the heritable form of the long Q-T syndrome include marked T-U wave abnormality, T-wave alternans, history of syncope or an episode of ventricular tachyarrhythmia, family history of unexplained sudden cardiac death before age 40, and congenital deafness. Mitral valve prolapse, with the click-murmur finding on auscultation and frequent ventricular ectopic beats, is fairly common in the general population. Sud-
Figure 1. Retrospective analysis of sudden cardiac death in 229 post-MI patients during a two-year period showed that 74 died within a minute of symptom onset, 10 between one and five minutes, 17 between 10 and 30 minutes, 5 between 40 and 60 minutes, and 123 after more than one hour.
den death has been reported in association with this disorder. Moreover, among patients with MVP. a high-risk subset can be identified by the presence of a combination of the following diagnostic findings: unexplained syncope; a prominent MVP murmur; female sex in the 30-to-40 age group; ST depression and Twave inversion in the inferior limb leads of the ECG, together with borderline or frank Q-T prolongation; and frequent or repetitive ventricular ectopic beats. Congenital heart defects are readily diagnosed and treated surgically, but patients are often left with a scar. It is believed that
such scars can serve as the nidus for the development of complex rhythms, and even predispose to malignant arrhythmia. The problem has only recently been recognized. In patients with underlying heart disease, some medications can trigger rhythm disorders. Use of such drugs in patients susceptible to rhythm disorders may be considered an additional risk factor. Among the drugs with recognized triggering activity are some used to treat heart disease, including some antiarrhythmic agents, the new antianginal medication bepridil, and cardiac glycosides that have been used for over two centuries.
Hospital Practice November 15. 1992
167
rhythmic agents in terms of ventricular arrhythmia suppression. However, in 1989 (two years into the planned three-year CAST study), it became evident that use of these agents was associated with increased mortality. Furthermore, the mortality among patients receiving either of the drugs was predominantly due to sudden cardiac arrest. The drugs were recategorized as proarrhythmic agents, but the mechanism of their proarrhyth-
Downloaded by [La Trobe University] at 20:00 30 May 2016
A dramatic example of adverse arrhythmic activity emerged unexpectedly from the Cardiac Arrhythmia Suppression Trial (CAST). The multicenter study, sponsored by the National Institutes of Health, was designed to test the hypothesis that suppression of ventricular ectopic beats would reduce the incidence of sudden cardiac death in post-MI patients. Two of the study drugs, encainide and flecainide, had been shown to be effective antiar-
Figure 2. When Joel Morganroth and James E. Goin analyzed data from four trials comparing quinidine with other class I antiarrhythmic agents, observed mortality associated with quinidine was higher than that associated with flecainide, mexiletine, or propafenone, and equal to that associated with tocainide.
168
Hospital Practice November 15. 1992
mic activity remains unclear. Quinidine is the oldest and still the most frequently prescribed of the traditional class I antiarrhythmics available in this country. Its safety and efficacy have never been rigorously tested, although it has long been known to have proarrhythmic activity. Evidence that quinidine may actually enhance the risk of mortality in patients being treated for arrhythmia comes from a study by Joel Morganroth and James E. Goin at the University of Pennsylvania. They performed a meta-analysis of data from four drug trials in which quinidine was compared with other class I an tiarr hythmics-flecainide, mexiletine, tocainide, or propafenone-for short-term treatment of benign or malignant ventricular arrhythmias in 1,009 patients. Observed mortality was proportionately greater among the 502 patients taking quinidine ( 12 deaths) than among 507 patients taking one of the other drugs (4 deaths) (Figure 2 l. The risk of dying while on quinidine was also significantly higher. Another drug with known proarrhythmic activity is the antianginal agent bepridil. It can produce life-threatening complex rhythms, particularly in vulnerable patients taking other heart medications. A relationship between digitalis therapy and increased mortality in survivors of myocardial infarction has been noted in a number of studies, but its significance is unclear. It has been suggested that the finding is merely an artifact. In one of our studies, we found that mortality at four months postinfarction was highest in patients treated with digitalis who had evidence of left ventricular dysfunction and (continues)
Downloaded by [La Trobe University] at 20:00 30 May 2016
SUDDEN DEATH
(continued)
complex ventricular rhythms at hospital discharge. In the study of instantaneous cardiac death mentioned previously, we found a strong association with digitalis therapy. Sixty-six of the 7 4 patients who died instantaneously were taking digitalis during the week before death, compared with 39 of 155 whose deaths were classified as noninstantaneous. Both studies were carefully controlled for confounding clinical factors. If digitalis in fact has an independent effect on mortality, our findings suggest that it enhances the risk of arrhythmia. Other drugs that may have an adverse effect on heart rhythm in susceptible patients include diuretics that alter the potassium content of the body, terfenadine (an H 1-receptor antagonist widely prescribed for allergic rhinitis), and some psychotropic agents, such as chlorpromazine and thioridazine. In emphasizing risk factors for sudden cardiac death and the need to identify patients who can benefit from preventive therapy, it should be noted that there are two therapeutic options: drugs and the automatic implantable cardioverter-defibrillator. Patient selection is extremely important in determining how effectively we use each option. Let us consider drug therapy first. In patients with symptomatic, complex ventricular arrhythmias, physiologic testing may be used to identify an antiarrhythmic drug that will suppress the induced malignant arrhythmia. ,8-Blockers stand out as a class of drugs effective in reducing the rate of both sudden and nonsudden cardiac death in high-risk patients. The classic Beta Blocker Heart Attack Trials estab-
Figure 3. In transthoracic implantation of the cardioverter-defibrillator, two sensing electrodes are placed in the ventricular myocardium, and anodal and cathodal patches are placed on the anterior right ventricle and left ventricular apex, respectively. Lead conductors are tunneled under the skin to the pulse generator, which lies in a subcutaneous pocket of the left upper abdomen.
lished that propranolol reduced mortality by approximately 25% compared with placebo. The ,8blockers are class II antiarrhythmic agents that have demonstrated long-term safety and do not appear to have any proarrhythmic activity. For patients with inducible arrhythmias that are not suppressible with class I or class II antiarrhythmics, the class III drugs amiodarone and sotalol have shown some efficacy in preventing sudden cardiac death in clinical trials. A meta-analysis of randomized trials of amiodarone suggested a 34% reduction in mortality in post-MI patients. 1\vo large-scale trials in
Europe and Canada have been organized to assess amiodarone's effect on survival in high-risk postinfarction patients. The results of these studies will be available in two or three years. The alternative to drug theraPY is the automatic implantable cardioverter-defibrillator (Figure 3). The first such device was developed by Michel Mirowski and his co-workers at Sinai Hospital of Baltimore and Intec Systems, Pittsburgh. An automatic defibrillator device was implanted in a patient who had had an out-of-hospital cardiac arrest. When the patient had another spontaneous episode several
Hospital Practice November 15. 1992
173
Downloaded by [La Trobe University] at 20:00 30 May 2016
months later, the device shocked him out of the potentially fatal rhythm and he survived. Thereport of this single case in the New England Journal of Medicine in 1980 provoked widespread interest. Over the past 12 years, the device has undergone technological improvements. For example, as both a cardioverter and a defibrillator, it now can convert tachycardia before the heart actually fibrillates, and it can terminate fibrillation within eight to 10 seconds. Currently, the only device approved by the Food and Drug Administration uses electrodes placed on the heart and therefore requires open thoracotomy for implantation. Usually, two sensing electrodes are placed in the ventricular myocardium, an anodal patch is placed on the anterior right ventricle, and the cathodal patch on the left ventricular apex. The lead conduc-
tors are tunneled under the skin to the pulse generator, which is placed in a subcutaneous pocket in the left upper abdominal wall. To date, approximately 30,000 automatic cardioverter-defibrillators have been implanted worldwide. The latest evolution in the technology is transvenous implantation of a three-lead system. 1\vo electrodes are placed endocardially via a cardiac catheter: one in the right ventricular apex and one at the junction of the superior vena cava and right atrium. The patch electrode is surgically placed in the left thoracic wall, and its lead is crossconnected with a Y connector to the right atrial lead to create a bidirectional current. The lead conductors are tunneled subcutaneously along the left thoracic wall to the pulse generator, which is placed in the abdominal wall. About 500 units have thus
Ventricular Fibrillation Detected
Figure 4. A three-lead ECG recorded events in the operation of an implantable cardioverter-defibrillator: detection of
17 4
Hospital Practice November 15. 1992
Start Charge
far been implanted via the transvenous approach. The same battery-powered pulse generator, which can deliver approximately 100 discharges, is used with both electrode systems. It can also store information, such as the number of times it has discharged, and this information can be retrieved. A recent improvement in the unit is the capacity to record the type of rhythm the patient had when it discharged. Further improvements will undoubtedly lead to smaller pulse generators with increased memory. At present, the automatic implantable cardioverter-defibrillator has been approved for the treatment of patients who have had an aborted out-of-hospital cardiac arrest and patients who have evidence oflife-threatening hypotensive ventricular tachycardia. We have already noted that patients with heart disease
End Charge
First Shock Delivery
ventricular fibrillation, initiation and completion of charging, and delivery of a shock. Sinus rhythm was restored.
Downloaded by [La Trobe University] at 20:00 30 May 2016
who have survived an episode of cardiac arrest have a 50% risk of a second, fatal event within two years. Ventricular tachycardia is not necessarily a malignant arrhythmia, but when accompanied by a drop in blood pressure, it can quickly deteriorate into ventricular fibrillation. There is no question that the device will defibrillate the heart if the patient has a fibrillatory episode (Figure 4). Efficacy is well documented in many medical centers in the United States, Canada, and Europe. Clinical studies of patients with automatic implantable cardioverter-defibrillators have typically recorded mortality of 10% at one year and about 20% at two to three years. These figures represent a dramatic reduction from the expected greater than 50% mortality at two years (Figure 5). Unfortunately, most of the studies have been retrospective, with no control group, or with historical controls. In a review of 10 retrospective studies, Stuart J. Connolly at McMaster University, Hamilton, Ont .. and Salim Yusuf at the National Heart, Lung, and Blood Institute, Bethesda, noted that there were biases in patient selection in many studies that could have led to lower-risk patients receiving automatic implantable cardioverter-defibrillator therapy. Two troubling questions left unanswered by these studies are, Have we sufficiently defined the patient population that will benefit from the device? Is it clearly beneficial compared with the best medical therapy? To date, there are no results from prospective randomized controlled studies that could provide the answers, but five such studies are planned or have been initiated. The Hamburg Cardiac Arrest Study in Germany, comparing
Figure 5. Richard N. Fogoros and co-workers found that mean cumulative survival was 97% at 12 months, 90% at 24 months, and 85% at 36 months in 119 patients who had received an implantable cardioverter-defibrillator and were followed for a mean of 21 months. In contrast, projected survival of these patients in the absence of implantation was calculated by the investigators to be 59% at 12 months, 39% at 24 months, and 31% at 36 months.
the automatic implantable cardioverter-defibrillator with antiarrhythmic drug therapy in survivors of cardiac arrest, is the first to issue interim results. With an 11-month mean followup of 139 patients randomized to receive implant treatment. amiodarone, propafenone, or metoprolol, the rate of sudden death in the cardioverter-defibrillator group was zero, in the amiodarone group, 9%, and 11% each in the groups receiving metoprolol and propafenone. Overall mortality was not significantly different between the implant patients ( 14%) and those patients on medical therapy ( 14% metoprolol. 15% amiodarone, 20% propafenone) in this short-term follow-up. The Canadian Implantable
Defibrillator Study (CIDS) will ultimately involve about 400 patients who have survived cardiac arrest, with at least 100 already entered. Patients are randomized to receive an automatic implantable cardioverter-defibrillator or to be treated with amiodarone. Another large-scale prospective study of patients who had an aborted cardiac arrest has been funded by the NHLBI. The study, which has not begun, calls for recruitment of 700 to 800 patients who will be randomized to receive either an automatic implantable cardioverter-defibrillator or conventional medical therapy. J. Thomas Bigger, Jr., of Columbia University is heading the multicenter CABG Patch Trial. a projected two- to five-year
Hospital Practice November 15, 1992
175
study of about 800 patients. This trial is enrolling patients under age 80 who are candidates for elective coronary artery bypass surgery and who have an ejection fraction of less than 0.36 and a positive signal-averaged ECG (a sensitive marker in patients at risk for lethal ventricular ar-
rhythmias). Patients are randomized at the time of surgery to receive an automatic implantable cardioverter-defibrillator as well or coronary bypass only. Morbidity and mortality with or without the cardioverterdefibrillator will be compared. The Multicenter Automatic De-
Selected Reading Moss AJ: Identification of patients at increased risk for potentially malignant arrhythmias. Cardiovasc Drugs Ther 4: 665, 1990 Moss AJ. Robinson J: Clinical features of the idiopathic long QT syndrome. Circulation 85 (suppli):I-140, 1992
Downloaded by [La Trobe University] at 20:00 30 May 2016
Wilber DJ et al: Electrophysiological testing and nonsustained ventricular tachycardia: Use and limitations in patients with coronary artery disease and impaired ventricular function. Circulation 82: 350, 1990 Waller T J et al: Reduction in sudden death total mortality by antiarrhythmic therapy evaluated by electrophysiologic drug testing: Criteria of efficacy in patients with sustained ventricular tachyarrhythmia. JAm Coll Cardiol10: 83, 1987 Furberg CD. Yusuf S: Antiarrhythmics and VPD suppression. Circulation 84:928, 1991 Echt DS et al: Mortality and morbidity in patients receiving encainide, flecainide, or placebo: The Cardiac Arrhythmia Suppression Trial. N Engl J Med 324 : 781, 1991 Morganroth J, Goin JE: Quinidine-related mortality in the short-to-medium-term treatment of ventricular arrhythmias: A meta-analysis. Circulation 84: 1977, 1991 Connolly SJ, YusufS: Evaluation of the implantable cardioverter defibrillator in survivors of cardiac arrest: The need for randomized trials (editorial). Am J Cardiol69: 959, 1992 Fogoros RN et al: Efficacy of the automatic implantable cardioverter-defibrillator in prolonging survival in patients with severe underlying cardiac disease. JAm Coll Cardiol 16: 381. 1990 Lehmann MH et al: The automatic implantable cardioverter defibrillator as antiarrhythmic treatment modality of choice for survivors of cardiac arrest unrelated to acute myocardial infarction (editorial). Am J Cardiol 62:803, 1988 Saksena S: Clinical progress in endocardial defibrillation. Clin Cardiol 12:709, 1989 Gabry MD et al: Automatic implantable cardioverter-defibrillator: Patient survival. battery longevity and shock delivery analysis. JAm Coll Cardiol 9:1349,1987 Saksena Setal: Long-term multicenter experience with a second-generation implantable pacemaker-defibrillator in patients with malignant ventricular tachyarrhythmias. JAm Coll Cardiol 19: 490, 1992 Newman D et al: Survival after implantation of the cardioverter defibrillator. Am J Cardia! 69 : 899. 1992 Tchou PJ et al: Automatic implantable cardioverter defibrillators and survival of patients with left ventricular dysfunction and malignant ventricular arrhythmias. Ann Intern Med 109:529, 1988 MAD IT Executive Committee: Multicenter Automatic Defibrillator Implantation Trial (MADIT): Design and clinical protocol. PACE Pacing Clin Electrophysiol14: 920 (part II), 1991
176
Hospital Practice November 15, 1992
fibrillator Implantation Trial (MAD IT) has been under way for over a year and has enrolled more than 60 patients. The major requirements for study entry are an episode of nonsustained ventricular tachycardia, a prior Q-wave infarction, a reduced ejection fraction, and inducible but nonsuppressible ventricular tachycardia on electrophysiologic testing. Patients with these characteristics are randomly assigned to receive either an automatic implantable cardioverter-defibrillator or conventional medical therapy. The medication prescribed is left to the patient's cardiologist. Medical therapy can also be given to patients who receive a unit. Thus, the only essential difference between the two groups should be the automatic implantable cardioverter-defibrillator. The study will be terminated at the earliest evidence that the device either is or is not effective in increasing survival. Performing randomized controlled studies in a patient population with a baseline 50% mortality risk poses tough ethical questions. It can be argued that a potentially lifesaving treatment should not be withheld from such patients. On the other hand, without controlled studies, it is impossible to substantiate that such therapy is clearly beneficial. During the 1980s, the automatic implantable cardioverterdefibrillator evolved technologically, and we gained experience with it. Certainly, it has been well documented that the device works in the setting of an acute fibrillation. Now it is time to define the population that will benefit from this new technology so that it is used appropriately and not abused. That is how we advance the science of clinical medicine.
