Gene Linked to Sudden Cardiac Death

Findings may benefit heart failure patients

THURSDAY, Dec. 13, 2001 (HealthDayNews) -- In a development that may lead to new treatments for heart failure patients, scientists have identified a gene in mice that seems to turn off an electronic regulator in the heart, making it easier for a disruption to cause sudden death through a massive short circuit.

The findings will not immediately help current heart failure patients, who often drop dead even if they're in the early stages of the disease. But further research may bring doctors new tools to identify those at highest risk before it's too late, say authors of a new study.

"We think we've made a big discovery in understanding the way the disease occurs," says co-author Dr. Kenneth R. Chien, director of the Institute of Molecular Medicine at the University of California (UC), San Diego.

Heart failure strikes some 550,000 Americans each year. After a heart attack, cardiovascular disease or other stresses, the heart muscle becomes weak and loses its ability to pump properly.

Ironically, heart failure is becoming more common even as life spans increase and medicine reaches new heights. Doctors attribute the rise in cases to the growing number of people who are surviving heart attacks.

A surprisingly high number of heart patients suffer from sudden death, typically when the heart short-circuits and loses its ability to pump in a coordinated way. "The heart can't contract. All it's doing is wiggling, a phenomenon known as fibrillation," says Dr. Eric J. Eichhorn, professor of medicine at the University of Texas Southwestern Medical Center.

Doctors often try to shock the heart back into a normal rhythm with a pair of electrified paddles, a procedure seen commonly on TV medical shows like "ER," but patients often die anyway.

The UC researchers suspected that a specific gene may turn defective during heart failure and contribute to sudden death. To test their theory, they used genetic engineering to breed mice that lacked the gene, called Kv Channel-Interacting Protein 2, or KChIP2.

While the mice appeared normal, a single extra heartbeat sent them into massive fibrillation to a level that would probably kill a human. Normal mice did not suffer the same problem when they had an extra heartbeat.

The findings are published in the Dec. 14 issue of the journal Cell.

A minor disruption -- such as an extra heartbeat, exercise or consumption of caffeine -- can trigger deadly irregular heartbeats in humans.

It appears that the KChIP2 gene in humans gets turned off during heart failure, a process that in turn switches off an electrical regulator, Chien says. The cause isn't known but may have something to do with chemicals released in the bodies of heart failure patients, he says.

The next step in research is to determine if there's a way to keep the gene "on," he says. "We hope to identify the pathway that leads to turning off the KChIP2 gene, then [investigate] whether directly blocking that pathway would eliminate or markedly reduce susceptibility to ventricular arrhythmia" -- deadly fibrillation.

The research into the gene may bring attention to the neglected problem of sudden death among heart failure patients who seem to be in fairly good shape, says Dr. Charles L. Schulman, assistant clinical professor of medicine at Harvard Medical School.

"You might expect a patient who was terribly sick and in the hospital and receiving drugs intravenously to be prone to sudden death, but you wouldn't expect it of someone who was on medication and doing fairly well," he says.

Doctors will be able to better use heart technology if they can predict who will be most susceptible to sudden death, he says. "It helps you to target your therapy to those who will benefit the most."

What to Do: The American Heart Association and the National Heart, Lung, and Blood Institute offer information on keeping your heart healthy.

SOURCES: Interviews with Kenneth R. Chien, M.D., Ph.D., director, Institute of Molecular Medicine, UC, San Diego; Eric J. Eichhorn, M.D., professor of medicine, University of Texas Southwestern Medical Center, Dallas; Charles L. Schulman, M.D., senior physician, Beth Israel Deaconess Medical Center, Boston, and assistant clinical professor of medicine, Harvard Medical School, Boston; Dec. 14, 2001, Cell
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