Sudden Cardiac Death in Chronic Coronary Artery Disease is caused by Ventricular Fibrillation in the Absence of MI

BUFFALO, N.Y. -- Sudden cardiac death (SCD), a situation in which the heart ceases to function without warning, resulting in death within minutes, is precipitated by a devastating disruption of the heart rhythm that can occur without evidence of an acute or healed heart attack, cardiovascular researchers from the University at Buffalo have shown.

In a presentation Nov. 10 at the American Heart Association meeting in Orlando, senior author John M. Canty, Jr., M.D., Albert & Elizabeth Rekate Professor of Medicine and director of UB's Center for Cardiovascular Research, described early findings from the center's investigations of sudden cardiac death based on a novel pig model of the condition.

Earlier post-mortem studies had confirmed that persons who succumb to sudden cardiac death frequently don't have evidence of a healed or acute heart attack. UB researchers suspected that susceptibility to sudden death could arise from cellular remodeling resulting from chronic repetitive ischemia or angina, which, in its most advanced form, is called hibernating myocardium, and set out to investigate the hypothesis.

In this condition, myocytes, cells in the heart's muscular tissue, shut down in areas subjected to reduced blood flow from narrowed arteries. This adaptation, a survival mechanism that allows the cells to remain viable and return to normal activity when normal blood flow is restored, also creates regions of muscular tissue with differing electrophysiological properties existing side-by-side. This heterogeneity sets the stage for ventricular fibrillation, UB researchers have shown.

"Normal heart tissue existing in close proximity to hibernating tissue causes a disruption in the electrical signals between cells necessary to maintain a steady heart rhythm," said Canty. "We've shown that this situation leads to tachycardia, or irregular heart contractions in the left ventricle, the major pumping chamber of the heart. If normal rhythm isn't restored within minutes, the heart goes into ventricular fibrillation and death is immediate."

The UB group is one of the few capable of studying this phenomenon directly. They developed the first chronic animal model of the condition by creating hibernating myocardium in pigs and equipping the animals with instruments that monitor the heart's cellular activities before and during a sudden cardiac death episode. By analyzing data recorded from 7 SCD pigs and 11 survivors, all of whom had been instrumented to produce the same amount of coronary artery occlusion and hibernating myocardium, the researchers were able to confirm that there was no evidence of heart attack in the SCD pigs, or that occlusion led to arrhythmias.

"Advances in understanding of the mechanisms leading to sudden death have previously been limited by our inability to reproduce chronic coronary artery disease in an animal model," said Canty. "This work is the first step in identifying the myocardial substrate that leads to electrical instability in the absence of a heart attack. The results are potentially relevant to understanding why patients without prior symptoms can develop ventricular fibrillation."

Gen Suzuki, M.D., Ph.D., postdoctoral research fellow in the research center is first author on the study. James A. Fallavollita, M.D., UB associate professor of medicine is a co-author.

The research was supported by grants from the John R. Oishei Foundation, the Mae Stone Goode Trust, the American Heart Association, the National Heart, Lung and Blood Institute, and the Department of Veterans Affairs.

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