Release Date: September 16, 2004
BUFFALO, N.Y. -- Sudden cardiac death each year claims the lives of more than 350,000 seemingly healthy men and women in the U.S., yet physicians continue to be perplexed about its underlying causes.
A new study by investigators in the University at Buffalo Center for Research in Cardiovascular Medicine, one of the largest undertaken on sudden cardiac death (SCD), may help provide some answers.
Using positron emission topography (PET), the UB researchers will establish baseline heart function and related physiological measures in patients whose physicians consider them at potential risk for SCD and track their medical progress over the next five years.
The study, which is expected to enroll 360 patients, will be supported by a $3.56 million grant from the National Heart, Lung and Blood Institute.
Sudden cardiac death results from a catastrophic disruption in heart rhythm. Although patients who die as a result commonly are described as having had a "massive heart attack," the event is better characterized as an "electrical accident," said John M. Canty, M.D., professor of medicine and Albert and Elizabeth Rekate Chair in Cardiovascular Disease in the UB School of Medicine and Biomedical Sciences. Canty and James A. Fallavollita, M.D., UB associate professor of medicine in the Division of Cardiology, are co-principal investigators on the study.
"We currently have limited ability to identify the majority of patients at risk of SCD beyond the traditional risk factors for coronary heart disease," said Canty. "We know from autopsy results that most people who suffer sudden cardiac death have advanced coronary artery disease, but those who survive by rapid cardiac resuscitation frequently show no evidence of an acute heart attack or any symptoms of heart disease immediately prior to the aborted cardiac arrest."
Study investigators hypothesize that the presence of adaptations that develop in the heart in response to repetitive episodes of inadequate blood flow lead to electrical instability of the heart and may predict SCD. These adaptations, termed hibernating myocardium, occur commonly in one or more regions of the heart in many patients with depressed heart function, said Canty. The grant will be used to study this scenario in patients with depressed heart function considered at high risk for SCD.
The overall objective of the current study is to use PET images of blood flow, tissue viability and sympathetic nerve function, in conjunction with evidence of depressed heart function, to predict better which patients with heart disease require an implantable defibrillator to prevent SCD. The researchers also will determine how these "substrate" parameters change after an impending cardiac arrest is prevented by the defibrillator's discharge.
In a hibernating region of the heart, muscle cells don't receive enough blood due to long-standing coronary artery narrowing, but they adapt to this impairment by reducing their function and oxygen needs. This adaptive survival mechanism involves cellular changes that allow heart cells to remain alive, or viable. A total blockage of blood flow would lead to death and scarring of the heart muscle, resulting in non-viable myocardium or a "heart attack."
Hibernating myocardial cells, with their depressed function, appear to be out of sync with adjacent healthy myocardial cells. Not only do they function differently, said Canty, but they are somewhat larger than other cells and have a reduced supply of sympathetic nerves. This change in nerve supply can disrupt the normal heart rhythm, making the heart more vulnerable to fibrillation, which can cause death within minutes if the heart rhythm is not restored with a defibrillator.
Canty and colleagues also are studying this problem in the laboratory, where they create hibernating myocardium in pigs. When an animal goes into fibrillation, which would ordinarily be fatal, an implantable defibrillator delivers a shock, saving the animal and providing a living model of SCD to study. By monitoring what transpired in the heart cells leading up to a potentially fatal ventricular fibrillation, and analyzing the physiological and biochemical changes in the heart after a "rescued SCD syndrome," the researchers are gaining valuable and previously unknown information about hearts at risk of sudden death.
"Once an aborted sudden death episode occurs in pigs with hibernating myocardium, we can study the heart to identify the cellular and molecular changes that may contribute to the development of an arrhythmia," said Canty. "The clinical study we have designed stems directly from the laboratory work that we have conducted over several years and is an excellent example of translating basic science studies to advance the clinical care of patients with heart disease."
Patients accepted into the clinical study will undergo a PET scan to determine the presence and amount of hibernating myocardium, as well as alterations in sympathetic nerve function to the heart. Participants will be followed up by phone at three-month intervals to track their medical condition. A repeat PET scan will be performed in a small group of the patients if they receive a shock from their internal defibrillator.
"Through our research project and the aid of our volunteer participants, we hope to come up with a strategy to help physicians better predict the people who are most at risk of sudden cardiac death and therefore most likely to benefit from an implantable cardiac defibrillator," said Canty. "Our long-term goal is to develop better approaches to identify the lower-risk patients with coronary artery disease who still account for most of the sudden deaths each year.
"If we can identify new markers of SCD risk using approaches such as molecular imaging with PET, we can better target treatments to prevent it."
Co-investigators on the study are Michael S. Haka, Ph.D., of the UB-VA Center for Positron Emission Tomography, and Andrew J. Luisi, Jr., M.D., Arturo M. Valverde, M.D., and Susan P. Graham, M.D., of the UB Division of Cardiology. Robert A. deKemp, Ph.D., of the Cardiac PET Center, University of Ottawa; Arthur J. Moss, M.D., of the University of Rochester School of Medicine and Dentistry, and Harold C. Strauss, M.D., chair of UB's Department of Physiology and Biophysics, are consultants in the study.
Preliminary research leading up to the clinical trial was supported in part by a grant from the John R. Oishei Foundation.
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