Predictors of Response to Biventricular Pacing in Heart Failure

Heart Failure (HF) is a disease of epidemic proportion in the U.S. affecting over 5 million individuals. It is estimated that in the next year nearly 400,000 new cases will be diagnosed, 1 million individuals will be hospitalized and 300,000 deaths will occur because of HF. Approximately half of the deaths will be attributed to worsening pump function while the remainder will be attributable to sudden cardiac death. Biventricular (BIV) pacing has recently emerged as an exciting new treatment of advanced HF with dramatic benefits to some patients. Current candidates include those with ventricular conduction abnormalities and reduced ejection fraction who continue to suffer from severe HF symptoms despite optimal pharmacological therapy. Recent clinical trials have demonstrated that BIV pacing improves myocardial function, functional capacity, quality of life, as well as reduces the incidence of hospitalization and even prolongs life. Despite all this, about one third of patients with HF do not benefit from BIV pacing, the so-called 'non-responders'. Our group and others have shown that there are direct genetic effects of BiV pacing in an animal model, however, there are gaps in existing knowledge about the effects of left ventricular (LV) pacing site or genetic influences on the degree of response to this novel therapy. This proposal aims at identifying predictors of benefit from Biventricular (BIV) pacing with the goal of optimizing the degree of benefit and increasing the proportion of patients who respond to this therapy. Patients who fulfill current indications for BIV pacing will undergo and echocardiography (echo) with regional tissue Doppler analysis and cardiac imaging consisting of a myocardial perfusion imaging(EGC rest gated Spect scan using Sestamibi) prior to implantation of a BIV pacing device. They will then be randomly assigned to empiric versus echo and Spect scan-guided LV lead positioning. In this latter group, optimal LV pacing site will be defined as the site of latest peak tissue velocity by tissue Doppler echo and Spect scan testing. In the empiric group, the LV lead position will be chosen by the masked operator based on the coronary sinus venous anatomy, on electrocardiographic (ECG) criteria, or other as per standard of care. Blood would be collected from all patients at the time of the procedure for analysis of genetic polymorphisms.