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Background: The frequency of sudden unexpected death is highest in the early post-myocardial infarction (MI) period; nevertheless, 2 recent trials showed no improvement in mortality with early placement of an implantable cardioverter-defibrillator after MI., Methods and Results: To better understand the pathophysiological events that lead to sudden death after MI, we assessed autopsy records in a series of cases classified as sudden death events in patients from the VALsartan In Acute myocardial infarctioN Trial (VALIANT). Autopsy records were available in 398 cases (14% of deaths). We determined that 105 patients had clinical circumstances consistent with sudden death. On the basis of the autopsy findings, we assessed the probable cause of sudden death and evaluated how these causes varied with time after MI. Of 105 deaths considered sudden on clinical grounds, autopsy suggested the following causes: 3 index MIs in the first 7 days (2.9%); 28 recurrent MIs (26.6%); 13 cardiac ruptures (12.4%); 4 pump failures (3.8%); 2 other cardiovascular causes (stroke or pulmonary embolism; 1.9%); and 1 noncardiovascular cause (1%). Fifty-four cases (51.4%) had no acute specific autopsy evidence other than the index MI and were thus presumed arrhythmic. The percentage of sudden death due to recurrent MI or rupture was highest in the first month after the index MI. By contrast, after 3 months, the percentage of presumed arrhythmic death was higher than recurrent MI or rupture (chi(2)=23.3, P<0.0001)., Conclusions: Recurrent MI or cardiac rupture accounts for a high proportion of sudden death in the early period after acute MI, whereas arrhythmic death may be more likely subsequently. These findings may help explain the lack of benefit of early implantable cardioverter-defibrillator therapy.

Background: Myocardial rupture is a relatively rare and usually fatal complication of myocardial infarction (MI). Early recognition of patients at greatest risk of myocardial rupture provides an opportunity for early intervention., Methods: VALIANT was a double-blind, randomized, controlled trial comparing valsartan, captopril, and their combination in high-risk patients post-MI. Myocardial rupture was identified by autopsy (available in 138/589 patients dying within 30 days of index MI), echocardiography, direct surgical visualization, or presence of hemopericardium. An independent clinical end points committee reviewed medical records for all deaths or suspected nonfatal cardiovascular events., Results: Rupture was identified in 45 (0.31%) patients enrolled in VALIANT, occurring 9.8 +/- 6.0 days after the qualifying MI. Rupture accounted for 7.6% (45/589) of all deaths occurring in the first 30 days of follow-up and 24% (33/138) of deaths in which autopsies were obtained. Compared with survivors, rupture was associated with increased age, hypertension, increased Killip class, lower estimated glomerular filtration rate, and Q wave MI, and inversely related to beta-blocker and diuretic use. Compared with patients who died of other causes within 30 days, patients with myocardial rupture were more likely to have had an inferior MI, Q wave MI, or hypertension; to have used oral anticoagulants; or to have received thrombolytic therapy., Conclusions: Although rare, myocardial rupture accounted for nearly one fourth of all deaths within the first 30 days after high-risk MI, suggesting an estimated incidence of approximately 1% within the first 30 days. A number of clinical characteristics may identify post-MI patients at higher risk of myocardial rupture., (Copyright (c) 2010 Mosby, Inc. All rights reserved.)

Background: Left ventricular systolic dysfunction (LVSD) and heart failure (HF) are powerful predictors of poor outcome after acute myocardial infarction (MI). It is not known, however, whether the extent of coronary artery disease (CAD) independently influences cardiovascular (CV) outcomes in these high-risk patients., Methods: In the VALIANT, 14703 patients were randomly assigned to receive either captopril monotherapy, valsartan monotherapy, or a valsartan and captopril combination between 0.5 and 10 days after acute MI complicated by LVSD, HF, or both. Cox proportional hazards models were used to evaluate the relation between the extent of CAD (the number of diseased vessels as assessed by angiography) and a range of CV outcomes and all-cause mortality., Results: Coronary angiography data were available on 5742 (40%) of the 14703 randomized patients. Single-vessel disease was reported in 1955 patients (34%), 2-vessel disease in 1598 (28%), and 3-vessel disease in 2189 (38%). For all CV outcomes, the risk increased with the severity of CAD (P for trend < .002). A comparison of single-, 2-, and 3-vessel disease showed that, after adjusting for all known covariates, including revascularization and ejection fraction, 2-vessel disease was associated with a 40% increased hazard (P = .008) and 3-vessel disease was associated with an 85% increased hazard (P < .001) for all-cause mortality. The fully adjusted hazard ratios for death and other CV outcomes increased significantly with increasing extent of CAD., Conclusions: Increasing extent of CAD, as detected by angiography, is a significant and independent risk factor for adverse CV outcomes after MI complicated by HF, LVSD, or both. The observed risk was apparent even after excluding patients who had undergone revascularization.

Background: The risk of sudden death from cardiac causes is increased among survivors of acute myocardial infarction with reduced left ventricular systolic function. We assessed the risk and time course of sudden death in high-risk patients after myocardial infarction., Methods: We studied 14,609 patients with left ventricular dysfunction, heart failure, or both after myocardial infarction to assess the incidence and timing of sudden unexpected death or cardiac arrest with resuscitation in relation to the left ventricular ejection fraction., Results: Of 14,609 patients, 1067 (7 percent) had an event a median of 180 days after myocardial infarction: 903 died suddenly, and 164 were resuscitated after cardiac arrest. The risk was highest in the first 30 days after myocardial infarction--1.4 percent per month (95 percent confidence interval, 1.2 to 1.6 percent)--and decreased to 0.14 percent per month (95 percent confidence interval, 0.11 to 0.18 percent) after 2 years. Patients with a left ventricular ejection fraction of 30 percent or less were at highest risk in this early period (rate, 2.3 percent per month; 95 percent confidence interval, 1.8 to 2.8 percent). Nineteen percent of all sudden deaths or episodes of cardiac arrest with resuscitation occurred within the first 30 days after myocardial infarction, and 83 percent of all patients who died suddenly did so in the first 30 days after hospital discharge. Each decrease of 5 percentage points in the left ventricular ejection fraction was associated with a 21 percent adjusted increase in the risk of sudden death or cardiac arrest with resuscitation in the first 30 days., Conclusions: The risk of sudden death is highest in the first 30 days after myocardial infarction among patients with left ventricular dysfunction, heart failure, or both. Thus, earlier implementation of strategies for preventing sudden death may be warranted in selected patients., (Copyright 2005 Massachusetts Medical Society.)