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Targeted drug therapy prevents exercise-induced arrhythmias

A 12-year-old Dutch boy bedridden for three years because of an inherited cardiac arrhythmia syndrome can now join his friends on the soccer field thanks to a discovery made by Vanderbilt University Medical Center researchers.

The investigators, led by Bjrn Knollmann, M.D., Ph.D., report this week in Nature Medicine that the clinically available drug flecainide prevents potentially lethal arrhythmias in patients with a specific type of exercise or stress-induced arrhythmia disorder called CPVT.

"It's potentially a breakthrough in the treatment of this rare syndrome," said Knollmann, associate professor of Medicine and Pharmacology.

Patients with CPVT experience abnormally rapid heart rates (tachycardia), usually during exercise or stress, and are at risk for fainting and cardiac arrest. The syndrome kills up to 50 percent of untreated patients, and it may account for some unexplained sudden cardiac deaths in young athletes.

Current treatment has been limited to two medications beta blockers, often used at very high doses, and calcium channel blockers to control the arrhythmias.

Implantable cardioverter defibrillators (ICDs) are placed in patients at high risk for sudden death, but ongoing arrhythmias can result in frequent stressful shocks.

The Dutch patient, for example, experienced ventricular tachycardia and ICD shocks whenever he got out of bed, Knollmann said.

Defibrillator therapy also can be problematic for pediatric patients (CPVT is usually diagnosed in children), who require multiple surgical revisions of their systems.

"For this particular disease, the ICD is a suboptimal treatment," he said. "It's extremely desirable to have a drug treatment that reduces or prevents the ventricular tachycardias, and therefore prevents the ICD shocks."

Knollmann and his team have been studying the molecular defects that trigger arrhythmias. They knew that mutations in two genes that enco

Contact: Craig Boerner
Vanderbilt University Medical Center

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