Fighting a Cardiac Killer
- Reported, February 29, 2012
(Ivanhoe Newswire)-- Sudden cardiac death due to electrical instability is the
leading cause of death in the United States accounting for 700-800 deaths per
day. SCDs are responsible for approximately 325,000 deaths each year in the
United States alone.
A breakthrough discovery has been made that researchers believe will be the
first step towards new diagnostic tools and therapies to prevent or treat the
occurrence of this fatal event.
SCDs occur most commonly in the morning hours, followed by a smaller peak in the
evening hours. While scientists have observed this tendency for many years,
prior to this breakthrough, the molecular basis for these daily patterns was
The research team led by Case Western Reserve University School of Medicine
discovered that a novel genetic factor, Kruppel-like Factor 15 (KLF15), links
the body's natural circadian rhythm to, and regulates the heart's electrical
activity. A lack or excess of KLF15, causes a loss or disruption in the heart's
electrical cycle and greatly increases susceptibility to arrhythmias. A lack of
KLF15 is seen in patients with heart failure, while its excess causes
electrocardiography (ECG) changes such as those seen in patients with Brugada
syndrome, a genetic heart rhythm disorder.
"Our study identifies a hitherto unknown mechanism for electrical instability in
the heart. It provides insights into day and night variation in arrhythmia
susceptibility that has been known for many years," Darwin Jeyaraj, MD, MRCP,
assistant professor of medicine at Case Western Reserve University School of
Medicine, cardiologist at Harrington Heart & Vascular Institute at University
Hospitals Case Medical Center, and lead author of this work, was quoted as
With this information, scientists can propose new patient therapies with the
goal of reducing occurrences of sudden cardiac death. For example, knowing that
KLF15 levels are reduced in heart failure patients, medications that increase
KLF15 levels, particularly at certain times of the day when sudden death is more
common, could reduce the incidence of this fatal disorder.
This significant finding proves that circadian rhythms are an important factor
in sudden cardiac death. In addition, it raises the possibility that additional
factors may affect the occurrence of sudden cardiac death. Further studies are
needed to examine how additional components of the biological clock can affect
electrical stability in the heart.
"This it is the first time a definitive link between circadian rhythms and
sudden cardiac death has been established," Mukesh K. Jain, MD, FAHA, professor
of medicine, Ellery Sedgwick Jr. Chair, and director, Case Cardiovascular
Research Institute at Case Western Reserve University School of Medicine and the
chief research officer, Harrington Heart & Vascular Institute at University
Hospitals Case Medical Center, was quoted as saying.
"We are just scratching the surface. It might be that, with further study,
assessment of circadian disruption in patients with cardiovascular disease might
lead us to innovative approaches to diagnosis, prognosis, and treatment. In
particular, such therapies could be beneficial for patients with heart failure
or hereditary mutations where nocturnal death is common."
SOURCE: Nature, February 22, 2012