Off tempo  pg. 2

Photo by Dean Dixon
Investigators around the world are turning to genetics to identify patients without “conventional markers” who are at risk for sudden cardiac death. Their efforts are grounded in three large epidemiological studies, the latest of which comes from a group headed by Arthur Wilde, M.D., Ph.D. at the Academic Medical Center in Amsterdam.

Wilde and colleagues performed a case-control study in patients with a defined type of myocardial infarction (ST-elevation MI) who underwent percutaneous coronary intervention (angioplasty or stent placement). The case patients were those who survived ventricular fibrillation that occurred within the first 12 hours of the myocardial infarction. Control patients were matched for age, gender and infarct size, but did not experience ventricular fibrillation.

“The most intriguing finding of this case-control study… is that sudden cardiac death among parents and siblings is such a strong predictor of primary ventricular fibrillation,” Wilde and colleagues wrote in their 2006 Circulation report. The previous epidemiological studies had also suggested that a family history of sudden cardiac death increases a person’s risk for sudden death.

“What a ‘family history’ means to me,” Roden says, “is that there’s a relatively common genetic variant, or set of variants, in people who have sudden death that is different from people who don’t have sudden death. And that risk shows up when a coronary artery is occluded.”

Roden and Jean-Jacques Schott, Ph.D., of the French INSERM (National Institute of Health and Medical Research Center) in Nantes, France, are co-coordinators of a five-year, $6 million initiative funded by the Paris-based Leducq Foundation to search for the genetic variations that increase risk for sudden cardiac death. The network of sites in Europe and the United States aims to generate a genetic risk profile that will make it possible to calculate a patient’s risk for sudden cardiac death based on a genetic test.

“For these kinds of genetic screens, you need large, well-characterized patient and control populations, and the resources to do complicated genetic and statistical analyses,” Roden says. The network, whose core members include Amsterdam’s Wilde, Eduardo Marban, M.D., Ph.D., and Peter Spooner, Ph.D., both of Johns Hopkins University, and Robert Myerburg, M.D., of the University of Miami, plans to carry out its first screen for genetic variations associated with sudden cardiac death within the next six months.

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