Risk of sudden arrhythmic death is high in CHD patients without severe systolic dysfunction

Sudden cardiac death accounts for a “substantial proportion” of overall mortality among coronary heart disease (CHD) patients who don’t have severe systolic dysfunction—that is, patients who aren’t candidates for implantable cardioverter defibrillators (ICDs), according to results of a study in JAMA Cardiology.

“The majority of sudden and/or arrhythmic deaths (SAD) in patients with coronary heart disease occur in those without severe systolic dysfunction, for whom strategies for sudden death prevention are lacking,” wrote investigators co-led by Christine M. Albert, MD, MPH, director, Center for Arrhythmia Prevention, Divisions of Preventive and Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, MA.

Sudden death accounts for 15% to 20% of deaths worldwide, and is frequently due to ventricular arrhythmias, Dr. Albert and colleagues noted. Implantable cardioverter defibrillators treat ventricular arrhythmias and improve survival in patients with CHD with symptomatic heart failure and a left ventricular ejection fraction (LVEF) less than 30% to 35%.

“Unfortunately, more than 70% of sudden deaths in coronary heart disease occur in individuals with LVEF greater than 35% who do not qualify for ICDs” under current clinical criteria, the authors wrote.

The aim of this study was to stratify the risk of SAD in this population and to identify which patients with CHD, but without severe systolic dysfunction, might benefit from ICD implantation to prevent sudden cardiac death. Investigators enrolled 5,761 participants (mean age 64 years; 76% male) with CHD and LVEF more than 35% (or LVEF of 30% to 35% and class I congestive heart failure) from 135 clinical sites in North America.

After accounting for competing causes of death, the cumulative 4-year incidence of SAD was 2.1% compared with a 7.7% incidence for non-arrhythmic (non-SAD) sudden deaths. The researchers defined sudden cardiac death as “a death or fatal cardiac arrest occurring within 1 hour of symptom onset without evidence for a noncardiac cause by history or autopsy.” They defined an arrhythmic death as “an abrupt spontaneous loss of pulse without evidence of preceding circulatory impairment or neurologic dysfunction.”

The proportion of deaths due to SAD varied widely, from 14% in patients with class II heart failure (18 of 131 deaths) to 49% in patients younger than 60 years (37 of 76 deaths).

The absolute risks of SAD were highest—about 5%—in those with the lowest LVEF (between 30% to 39%) and in those with the most advanced heart failure (class III/IV). However, “the cumulative incidence of non-SAD was similarly elevated in these latter high-risk subgroups,” the authors wrote.

These findings challenge the “contemporary paradigm” that stratifies SAD risk at an LVEF threshold of 35%, the investigators noted.

“In this study, SAD risk was continuously and inversely associated with LVEF, and further, the relative risk of SAD was greater than non-SAD in patients with an LVEF of 40% to 49%,” Dr. Albert and coauthors wrote. “Given that more than 70% of individuals experiencing sudden death have an LVEF greater than 35%, integration of a more continuous assessment of LVEF into future risk stratification efforts may improve SAD risk prediction.”

The researchers estimated how many lives could be saved by ICD implantation in certain subgroups in the study. In the group with the highest proportion of deaths due to SAD (49% in those younger than age 60), ICDs were projected to provide the greatest relative reduction in mortality (29%). However, the researchers acknowledged, this equated to ICD implantation in 83 patients to save 1 life.

The study did provide a foothold for better stratifying high-risk subgroups that might be targeted in future trials of SAD prevention. “Looking ahead, identification of markers that uniquely discriminate SAD from non-SAD will be required to maximize absolute and proportional risk in subpopulations targeted for sudden death prevention,” the authors wrote.

This research was supported by the National Heart, Lung, and Blood Institute, and by St. Jude Medical Inc. and St. Jude Medical Foundation.