Sudden Death in Patients with Myocardial Infarction and Left Ventricular Dysfunction or Heart Failure

abstract & commentary

By John P. DiMarco, MD, PhD

Synopsis: The absolute risk for sudden death or cardiac arrest is greatest in the early period after myocardial infarction, and the event rate declines significantly over time.

Source: Solomon SD, et al. Sudden Death in Patients With Myocardial Infarction and Left Ventricular Dysfunction, Heart Failure, or Both. N Engl J Med. 2005;352:2581-2588.

The valsartan in acute myocardial infarction Trial (VALIANT) was a randomized, controlled trial comparing valsartan, captopril, or combined therapy with both agents in over 14,000 patients with a recent myocardial infarction that had been complicated by heart failure and/or left ventricular systolic dysfunction. For the purpose of this analysis, patients who received an ICD before randomization were excluded. During follow-up, all deaths were reviewed in a blinded fashion. Sudden death was explicitly defined as death that occurred "suddenly and unexpectedly" in a patient in an otherwise stable condition.

During a median follow-up period of 24.7 months, 1067 of 14,609 (7%) patients experienced either sudden death (903) or were resuscitated after cardiac arrest (164). Five of the patients who were resuscitated after cardiac arrest died on the date of resuscitation. Of the 164 patients who were resuscitated, 108 (66%) remained alive at 6 months and 93 (57%) were alive at the end of the trial. Patients who died suddenly or who had cardiac arrests were significantly older, had higher baseline systolic and diastolic blood pressures, baseline heart rates and Killip class, had a lower left ventricular ejection fraction, were more likely to have a history of diabetes or hypertension, and were less likely to have received reperfusion therapy, amiodarone, or beta blockers. However, there were only relatively minor differences when the 1067 patients in the sudden death group were compared to the 1905 patients who died from causes other than sudden death. Sudden death and cardiac arrest were most common during the first 30 days after myocardial infarction. During this time period, 126 patients died suddenly and 72 patients were resuscitated from cardiac arrest. This represented 19% of all such events during the entire trial. The sudden death/cardiac arrest event rate was 1.4% per month during this period. From one month to 6 months, the event rate was 0.5% per month, from 6 months to 12 months the event rate was 0.27% per month, from one through 2 years, the event rate was 0.18% per month, and from 2 to 3 years, the event rate
was 0.14% per month. The increased early incidence of sudden death or cardiac arrest was most prominent in patients with the lowest ejection fractions. Among patients with an ejection fraction of 30% or less, the incidence rate during the first 30 days for sudden death or cardiac arrest was 2.3% per month. During the entire course of the trial, out of 399 of the 3852 patients, 10% with an ejection fraction of 30% or less, died suddenly, or had cardiac arrest, compared with 295 of the 4998 patients (6%) with an ejection fraction between 31% and 40%, and 119 of the 2406 (5%) patients with an ejection fraction of more than 40%. Although the relative rates differed based on the ejection fraction, the time-dependent feature was seen in
all groups. For the entire group, the rate of sudden death or cardiac arrest was more than 6 times as high in the first month as after one year.

Solomon and colleagues conclude that the absolute risk for sudden death or cardiac arrest is greatest in the early period after myocardial infarction, and that the event rate declines significantly over time. Solomon et al concluded that their data confirmed the high risk of sudden death early after myocardial infarction, and argue that these data suggest the need to consider early implementation of strategies to prevent sudden death after myocardial infarction.

Commentary

These data from the VALIANT trial confirm earlier observations that the overall mortality and, in particular, the sudden death mortality rate after myocardial infarction, is highest during the first 30 days after the event. Unfortunately, prophylactic antiarrhythmic drug therapy has not been shown to be effective in this population, and the single ICD trial that focused on this group (DINAMIT) also showed no benefit. In the latter trial, although ICD therapy decreased the incidence of arrhythmic death, this was compensated for by an increased number of deaths from other causes. As a result, the overall mortality was unchanged. This is supported by observations from the MADIT-II trial that have also showed that there was greater benefit in patients with more chronic myocardial infarction. In MADIT-II, no benefit was seen in patients who entered this trial within 18 months of their last myocardial infarction. Primarily on the basis of DINAMIT, currently those guidelines do not allow reimbursement for ICD implants within 40 days of myocardial infarction. How to manage high risk patients during this period, therefore, becomes a significant clinical issue, since neither antiarrhythmic drugs nor ICD therapy has shown benefit.

The patients in VALIANT all received an angiotensin converting enzyme inhibitor, an angiotensin receptor blocker, or both. Most also received beta blockers and aspirin. However, only a minority received either primary percutaneous intervention at the time of their infarct or thrombolytic therapy, and any form of revascularization was significantly more common in those among the long-term survivors. Therefore, one interpretation of these data and the data from DINAMIT and MADIT II might be that the risk for sudden death in the first month after myocardial infarction is different than during the more chronic phases. During this phase, mortality might be dominated by recurrent infarction, ischemia, or heart failure. In this setting, any benefits from an ICD might be blunted. For now, physicians caring for such patients should concentrate on optimizing therapy for ischemia and heart failure. n