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Background: Sudden death (SD) is a frequent catastrophic complication in patients after myocardial infarction. Circumstances of SD may affect strategies for prevention., Methods and Results: We reviewed source documentation for 1067 patients who had SD in the Valsartan in Acute Myocardial Infarction Trial (VALIANT) trial. We determined the circumstances of these events and assessed long-term mortality in patients who were resuscitated. Location of the SD event was available in 978 of 1067 patients, with 226 events occurring within the first 40 days. Although SD was more likely to occur at home (645 of 978, 66%) than in hospital (204 of 978, 21%), the proportion of in-hospital events was higher early on (99 of 226, 44%). Home events were less likely to be witnessed regardless of time frame. Preceding activity was known for 42% of patients with home arrest; of these, 52% were determined to be asleep at time of event, and these deaths were more likely to be unwitnessed. A majority of patients for whom initial ECG rhythm was reported had ventricular tachycardia/ventricular fibrillation (189 of 283, 67%). Of the 155 patients successfully resuscitated, 24% subsequently received an implantable cardioverter-defibrillator. Nineteen percent of those who received an implantable cardioverter-defibrillator subsequently died compared with 49% of patients who did not receive an implantable cardioverter-defibrillator (hazard ratio, 0.36; 95% confidence interval, 0.14 to 0.93; P=0.04)., Conclusions: A high proportion of SD events after high-risk myocardial infarction occurred at home, but in-hospital events were more common early on. Patients who were asleep were more likely to have unwitnessed arrests. Alternative strategies for the prevention of SD in patients who are not candidates for implantable cardioverter-defibrillator will need to take into account the circumstances of SD events.

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: Converting enzyme inhibitors are more effective than arteriolar vasodilators at regressing left ventricular hypertrophy in spontaneously hypertensive rats (SHR), possibly because of nonhemodynamic factors. However, the pulsatile component of hemodynamic load has not been evaluated in this model., Methods and Results: We measured pulsatile hemodynamics in 18-month-old male SHR after 6 months of therapy with either zofenopril (Z), hydralazine (H), or water (W). Hydralazine and zofenopril reduced mean arterial pressure comparably (W, 106 +/- 23 versus H, 81 +/- 12 versus Z, 84 +/- 18 mm Hg, P = .002) yet had a differential effect on the ratio of left ventricular weight to body weight (W, 3.9 +/- 0.5 versus H, 3.3 +/- 0.4 versus Z, 2.4 +/- 0.2 g/kg, P < .005). Hydralazine-treated SHR had increased characteristic impedance (P = .0011) and a persistently low ratio of the reflected-wave transit time to left ventricular ejection time (P < .001), which contributed to early and late systolic loading, respectively, of the left ventricle. Consequently, only zofenopril-treated SHR had a significant reduction in left ventricular systolic force-time integral (P = .02), a measure of total ventricular load. There were no differences in systolic stress-time integral, suggesting that mass was appropriate to load when all elements of steady-flow and pulsatile load were considered., Conclusions: A blunted reduction in total left ventricular load, due to increased pulsatile load in SHR treated with hydralazine, provided a hemodynamic basis for the differential regression of hypertrophy in this model of genetic hypertension.