Friday, June 24, 2005

Increased Risk of Sudden Death within 30 Days after a Heart Attack
By Julie McKeel

The risk of sudden death is highest in the first 30 days after a heart attack for patients with left ventricular dysfunction, heart failure, or both, according to a study published in the June 2005 issue of The New England Journal of Medicine. The study authors suggest that earlier preventive treatment strategies would help to offset this risk in selected patients.

The DCRI’s Dr. Robert Califf, Dr. Eric Velazquez, and Karen Pieper, M.S., were co-authors on this study.

The researchers studied 14,609 patients with left ventricular dysfunction, heart failure, or both after heart attack to determine how often and when sudden unexpected death or heart attack occurred for recovering patients.

Using the left ventricular ejection fraction (LVEF) as the common denominator, patients with an ejection fraction of 30 percent or less were at highest risk within the first 30 days of a heart attack, according to the study results. [The ejection fraction is a measure of the amount of blood pumped out of a filled ventricle. A normal EF is = 50%. This is also called left ventricular ejection fraction (LVEF).] Nineteen percent of all sudden deaths or cardiac episodes occurred within the first 30 days after heart attack, and 83% of all patients who died suddenly did so in the first 30 days after hospital discharge.

Although many patients die from an acute heart attack before reaching the hospital, those who survive the initial attack and are admitted to the hospital remain at substantial risk for abnormal heart rhythm events. The risk is greatest in the first few hours after the heart attack, but decreases quickly thereafter. The extent of injury to the heart and other factors influence this risk.

Reduced heart muscle function is a major risk factor for death, including sudden death, after a heart attack. This result has led to trials of implantable cardioverter defibrillators (ICDs) in patients with a low left ventricular ejection fraction after heart attack.

The authors studied patients enrolled in the Valsartan in Acute Myocardial Infarction Trial (VALIANT). This trial enrolled 14,703 patients and studied the treatment of these patients with valsartan, captopril, or both in with a first or subsequent acute heart attack complicated by heart failure, left ventricular systolic dysfunction, or both. All patients had an ejection fraction of no more than 40 percent or evidence of heart failure complicating their heart attack. In the current analysis of the VALIANT data, the researchers excluded 94 patients because they had already received an ICD.

Of the 14,609 remaining patients, 903 patients died suddenly and 164 were resuscitated after cardiac arrest. During the first 30 days after heart attack, 126 patients died suddenly and 72 patients were resuscitated after cardiac arrest, for an event rate of 1.4% per month.

These early events occurred most often among patients with an ejection fraction of 30 percent or less. Of the 156 sudden deaths or episodes of cardiac arrest with resuscitation that occurred during the first 30 days, 85 occurred among the 3852 patients with an ejection fraction of 30 percent or less. Of these patients, 399 (or 10%) died suddenly or had a cardiac event during the trial, as compared with 295 of the 4998 patients with an ejection fraction of 31 to 40 percent (6%) and 119 of the 2406 patients with an ejection fraction of more than 40 percent (5%).

The risk is greatest within the first week after heart attack and among patients with the lowest ejection fraction and declines significantly over time, remaining steady at about one year. While the increased early rate of sudden death was highest among patients with the lowest left ventricular ejection fraction, the high incidence was not restricted to patients with the lowest left ventricular ejection fraction. The risk was increased despite the fact that all patients, according to the study design, were receiving renin–angiotensin inhibitors and the majority were receiving beta-blockers and aspirin.

The authors showed that the risk of sudden death is highest soon after heart attack — particularly during the first 30 days. This risk is greatest among patients with the lowest left ventricular ejection fraction (30 percent or less), but even patients with a high ejection fraction (more than 40 percent) are at substantially increased risk in the first 30 days after a heart attack. While it is not yet known whether early ICD treatment would reduce these risks, the study data suggest the need to consider implementing strategies to prevent sudden death in selected patients before the time recommended by current guidelines.

Study authors, representing the Valsartan in Acute Myocardial Infarction Trial (VALIANT) Investigators, include Scott D. Solomon, M.D., Steve Zelenkofske, D.O., John J.V. McMurray, M.D., Peter V. Finn, M.D., George Ertl, M.D., Adam Harsanyi, M.D., Jean L. Rouleau, M.D., Aldo Maggioni, M.D., Lars Kober, M.D., Harvey White, D.Sc., Frans Van de Werf, M.D., Ph.D., Marc A. Pfeffer, M.D., Ph.D., and the DCRI’s Eric Velazquez, M.D., Karen Pieper, M.S., and Robert M. Califf, M.D.

This study was supported by a grant from Novartis Pharmaceuticals.

Rob Califf, M.D.

Eric Velazquez, M.D.

Karen Pieper, M.S.