Pathobiology of cardiac dyssynchrony and resynchronization

Cardiac resynchronization therapy (CRT) represents the major new advance for treatment of heart failure since the start of the new millennium. With this therapy, failing hearts with discoordinate contraction due to conduction delay are subjected to biventricular stimulation to "resynchronize" contraction and improve chamber function. Remarkably, CRT was mostly developed and tested in patients first, and the speed at which the concept was translated to an approved clinical therapy was unusually quick. To date, CRT is the only heart failure treatment that can both acutely and chronically improve the systolic pump performance of the failing human heart yet also enhance long-term survival. This situation underscores the importance of understanding how CRT works at the molecular and cellular levels, as these insights might shed light on new approaches to treating heart failure more generally. Over the past 7 years, my laboratory and others at Johns Hopkins have developed novel animal models for addressing this question, and new results are revealing intriguing insights into the mechanisms of CRT. This review, presented on the occasion of the Fourth Annual Douglas P. Zipes Lecture at the 2009 Scientific Sessions of the Heart Rhythm Society, highlights these advances and new directions in CRT research.