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.

The present proposal aims at 1) testing the hypothesis that tissue Doppler echocardiography can identify the optimal site of LV lead placement and improve the response to BIV pacing in HF, and 2) testing the hypothesis that genetic polymorphisms influence the incidence and degree of response to BIV pacing in HF. Our group has extensive experience in implanting BIV pacing devices, in quantifying ventricular dyssynchrony using unique echocardiographic (echo) imaging, and in testing genetic polymorphisms in a HF population. We plan to randomize 300 patients with clinical indication for BIV pacing to empiric versus echo-guided LV lead placement. Blood will also be collected at the time of the procedure for analysis of genetic polymorphisms. The ultimate goal of this study is to identify the mechanical and genetic predictors of response to BIV pacing for the purpose of optimizing the degree of benefit and increasing the proportion of patients who respond to this therapy. This project will also help identify patient at low risk of response to BIV pacing, in whom this expensive and invasive therapy should be avoided.

Inclusion Criteria:

• age greater than 18 years Heart Failure Ejection fraction<35% QRS complex>120 ms

Exclusion Criteria:

• pregnant unable to consent