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
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
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
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
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
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