The role of the implantable cardioverter-defibrillator for prevention of sudden cardiac death.

Sudden cardiac death affects approximately 350 000 people per year in the United States, and at least 1 million people per year develop conditions that place them at risk for sudden cardiac death in the future. Survivors of one sudden cardiac death episode have a recurrence rate of 35% to 50% in 2 years, which 85% of the time is the result of ventricular tachycardia or ventricular fibrillation. Although coronary revascularization, -blockers, angiotensin-converting enzyme inhibitors, some antiarrhythmic agents, and antiarrhythmic surgery can reduce the chance for sudden cardiac death, development of the implantable cardioverter-defibrillator (ICD) has had the greatest impact on specifically preventing sudden death. The ICD was the result of work by Michel Mirowski, who implanted the first defibrillator in a human in 1980 (1). The initial automatic implantable defibrillators were large, required a thoracotomy to place epicardial defibrillating patches, and were nonprogrammable. Shortly thereafter, synchronization to the QRS of ventricular tachycardia led to a change in name to automatic implantable cardioverter-defibrillator. With the development of devices by other companies, the generic term, ICD, has become most appropriate for these devices as a group. In 1985, the U.S. Food and Drug Administration approved the ICD, and in the past 15 years this device has evolved rapidly and gained widespread acceptance. The ICD has been substantially reduced in size; can be implanted transvenously as a pacemaker would be; and can be programmed for sensing, antitachycardia pacing, and defibrillating. The rapidity with which these changes have occurred testifies to the effectiveness of the device in converting fatal ventricular arrhythmias to sinus rhythm. Currently, ICDs may be single-chambered or dual-chambered, have sophisticated algorithms for detection of supraventricular and ventricular arrhythmias, and can be programmed to deliver multiple therapeutic options, all in a device approximately 40 mL in size. The historic evolution of the ICD is shown in Figure 1. The impact of these evolutionary changes on hospital costs and lengths of stay is shown in Figure 2. The risks associated with implantation of transvenous ICDs are comparable to those incurred with implantation of standard pacemakers; the only added risk is that associated with testing of the device. In our experience, implantation-related mortality is less than 0.5%. We discuss the current indications for ICD use in primary and secondary prevention of sudden cardiac death. Figure 1. Evolution of implantable cardioverter-defibrillator ( ICD ) therapy. Figure 2. Reduction in costs of implantation with the evolution of implantable cardioverter-defibrillators. ICD Therapy for Prevention of Sudden Cardiac Death in Patients with Documented or Suspected Ventricular Tachyarrhythmias This section discusses three types of patients: 1) those who have survived cardiac arrest or who have documented hemodynamically untolerated ventricular tachycardia [that is, with such symptoms as syncope, angina, or heart failure], 2) those with sustained ventricular tachycardia that is hemodynamically tolerated, and 3) those with syncope without documented arrhythmias but in whom ventricular tachyarrhythmias are considered the most likely cause. Patients with Aborted Cardiac Arrest or Hemodynamically Untolerated, Uniform Ventricular Tachycardia The potential benefit of ICD therapy for secondary prevention in patients with hemodynamically untolerated ventricular arrhythmias has been suggested for many years on the basis of observational and nonrandomized studies (2-5). Confidence in conventional antiarrhythmic therapy (that is, therapy other than amiodarone) to prevent sudden death has been eroded by such studies as the Cardiac Arrest Study in Seattle: Conventional Versus Amiodarone Drug Evaluation and, to a lesser extent, the Electrophysiologic Study Versus Electromagnetic Monitoring trial, as well as by an increased appreciation for the proarrhythmic side effects of antiarrhythmic therapy (6-9). Nonetheless, many doubted the ability of ICD therapy to provide a significant total mortality benefit, mostly because of the competing causes of death (10) in patients with ventricular arrhythmias and significant structural heart disease (of which refractory congestive heart failure is the most important). This was the setting for the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial (11), which provided the first randomized, controlled comparison of ICD therapy with best antiarrhythmic therapyessentially, empirical amiodarone therapyin patients with aborted cardiac arrest or poorly tolerated ventricular tachycardia. The trial, which included 1016 patients randomly assigned to ICD or drug therapy, was terminated prematurely after interim analysis demonstrated that ICD therapy reduced total mortality by 27% at 2 years (25% vs. 18%; absolute risk reduction, 7 percentage points; P<0.02) (11). The significance of this result was questioned on several fronts. First, the 27% reduction in mortality resulted in a mean duration of life saved of only 2.7 months at 3 years. However, the survival benefit in AVID may have been undermined by early termination of the trial, as well as by 18.9% crossover from amiodarone to ICD therapy. Second, many expressed concern that AVID was not representative of the larger population of patients with life-threatening ventricular arrhythmias. This criticism was somewhat muted by similar findings of the Canadian Implantable Defibrillator Study (CIDS) (12) and the Cardiac Arrest Study Hamburg (CASH) (13), in which ICD therapy provided a reduction in total mortality of 19.6% and 37% at 2 years, respectively (Table 1). However, the absolute risk reduction was 5 percentage points over 3 years in CIDS and 7.5 percentage points over 2 years in CASH, and the results of CIDS were not statistically significant (P=0.07). Moreover, CASH demonstrated a benefit of ICD therapy only when the amiodarone and -blocker groups were combined on a post hoc basis. These limitations may have resulted from lack of sufficient statistical power in both studies. In addition, both CIDS and CASH took 7 years to recruit patients, leading to concern over whether the population studied was representative of the population at risk. Finally, some wondered whether the apparent benefit was due instead to the nonequivalent use of -blockers in the ICD group (42%) relative to the amiodarone (17%) treatment group, even though ICD therapy demonstrated persistent benefit after post hoc adjustment for this variable. Increased use of -blockers in the ICD group also occurred in CIDS. It could also be argued that more patients in both groups may have benefited from -blockers (14-17), coronary revascularization (particularly in light of the Coronary Artery Bypass Grafting Patch Trial findings) (18), and angiotensin-converting enzyme inhibitors. Nonetheless, the AVID trial, CIDS, and CASH were consistent in their demonstration of the superiority of ICD therapy over antiarrhythmic drug therapy in patients with life-threatening ventricular arrhythmias. Table 1. Trials Comparing Implantable Cardioverter-Defibrillators with Antiarrhythmic Drug Therapy in Patients with Ventricular Tachycardia or Ventricular Fibrillation Despite the power of these results, some have argued against uniform prescription of ICD therapy for all patients with poorly tolerated ventricular arrhythmias. Subgroup analysis of the AVID trial suggested that ICD therapy conferred no advantage over treatment with amiodarone in patients with relatively preserved left ventricular function (ejection fraction>0.35) (19). We disagree with this idea. These patients, who have relatively little risk for cardiac death aside from arrhythmic death, should benefit from ICD therapy in the long term. Trial design factors, such as low event rates, short observation periods, and early trial termination, make this benefit difficult to prove statistically. Patients with very poor left ventricular function (ejection fraction<0.20) may not benefit from ICD therapy, particularly in the long run, because they have a high rate of death from comorbid conditions. Thus, patient selection and trial design markedly influence statistical results. Application of the data from these trials to individual patients needs to be done with caution because of the inherent limitations of randomized, controlled trials. Patients with Syncope Suspected To Result from Ventricular Tachyarrhythmias and Inducible Ventricular Arrhythmias with Programmed Ventricular Stimulation It is well known that patients with unexplained syncope and left ventricular dysfunction have rates of mortality and event-free survival similar to those in patients resuscitated from a cardiac arrest (11). This was confirmed in the small subgroup of patients with syncope and inducible ventricular tachycardia in the AVID trial (11). In the observational AVID registry (20), patients with unexplained syncope (mortality, 12.3% at 16.9 months) or syncopal ventricular tachycardia (mortality, 21.2%), had as poor a prognosis as patients resuscitated from cardiac arrest (mortality, 17.0%). This finding led investigators to suspect that similar mechanisms were at work in these two patient populations. To date, no randomized trial has evaluated the most appropriate therapy for such patientsICDs. However, these data suggest that the benefit of ICD therapy in patients with syncope should equal that observed in the higher-risk patient cohorts discussed in the preceding section. In a retrospective analysis of our own data, the frequency of appropriate ICD therapy during follow-up in patients who had an ICD implanted for unexplained syncope believed to be due to ventricular tachyarrhythmias was similar to that among survivors of cardiac arrest (21). Link and coworkers (22) reported that patients with syncope and inducible ventricular