Project Grant R01HL177564

The National Heart, Lung, and Blood Institute awarded Vanderbilt University Medical Center $856,721 on August 5, 2026, under the Cardiovascular Diseases Research program (CFDA 93.837) to develop flecainide analogs that selectively inhibit the cardiac ryanodine receptor (RYR2) for arrhythmia prevention.

The project addresses a critical gap in antiarrhythmic therapy. Sudden cardiac death from ventricular arrhythmias accounts for 10–20 percent of adult deaths in the United States, and implantable defibrillators remain the only effective treatment for high-risk patients because traditional ion-channel-targeting antiarrhythmic drugs have proven ineffective or harmful. Flecainide, an established antiarrhythmic, suppresses both sodium channels and RYR2, and prevents arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), but its sodium-channel-blocking effects create safety risks, particularly in ischemic heart disease. Recent evidence suggests flecainide's antiarrhythmic efficacy in CPVT derives primarily from RYR2 inhibition rather than sodium-channel suppression. The research team has identified flecainide analogs that efficiently inhibit RYR2 while minimizing sodium-channel activity, offering potential for safer antiarrhythmic therapy with fewer side effects.

Work is performed at Vanderbilt University Medical Center in Nashville, Tennessee. The period of performance runs through May 31, 2030. This is a Project Grant, a standard NIH research award type.