Heart Failure (HF) is a disease of epidemic proportion in the US affecting over 5 million individuals. Cardiac resynchronization therapy (CRT) is an established therapy for many patients with advanced HF. CRT can be delivered through a pacemaker (CRT-P) or a defibrillator (CRT-D). CRT-P devices are smaller and cost a fraction of the price of CRT-D devices. Compared to optimal pharmacological treatment, both CRT-P and CRT- D are proven to reduce mortality and improve quality of life (QOL). When compared to each other in one study however, CRT-D exhibited a non-significant trend towards lower all-cause mortality compared to CRT-P when patients of all ages were included. As people in the United States and Europe get older, the proportion of older patients (?80 years) is growing. Although not excluded from the large CRT randomized trials, these patients have been largely underrepresented in these trials but still receive up to 20% of all CRT-D?s implanted in the U.S. As they get older, patients have a higher risk of death from competing morbidities and lower odds of receiving defibrillator shocks as demonstrated in large patient registries. Based on these data, it is very likely that in older patients, CRT-P is non-inferior to CRT-D for the endpoints of all-cause mortality and QOL but still offers important gains over CRT-D given its smaller size and lower cost. Published guidelines do not distinguish between the clinical indications for CRT-P and CRT-D. Also, wide gaps in knowledge exist regarding the impact of CRT-P versus CRT-D on the outcomes of mortality and QOL in older patients. To answer these important questions, a large, non-inferiority trial randomizing older patients to CRT-P vs. CRT-D is needed. Such a trial is likely to show that CRT-P is non-inferior to CRT-D for the endpoints of mortality and QOL, and this would lead to modifications in published guideline recommendations for CRT, changes in clinical practice, and reductions to the cost of HF management. The goal of this R34 application is to pilot test a randomized, controlled, non-inferiority trial comparing the survival and QOL of older patients receiving CRT-P versus CRT-D therapy. This pilot will enroll 50 HF patients (age ? 80 years) undergoing CRT device implantation at the hospitals of the University of Pittsburgh Medical Center, Duke University, Ohio State University, and the VA Pittsburgh Healthcare System. Patients will be randomized to CRT-P versus CRT-D and followed until study end. Rates of patient screening, enrollment, randomization, and retention as well as cost of care will be examined. The results of this pilot study will inform the design of a large pivotal non-inferiority trial and will be necessary for its success. Patients who refuse participation in the randomized pilot trial will be enrolled and followed as part of a prospective observational cohort. Characteristics of patients who choose CRT-P vs. CRT-D will be compared and patients? level of satisfaction with their device decision will be measured.
The proposed R34 pilot study will provide essential and sufficient information about the acceptance of older heart failure patients with depressed cardiac muscle function to enroll in a randomized, non-inferiority clinical trial examining the effect of cardiac resynchronization therapy (CRT) using a pacemaker (CRT-P) versus a defibrillator (CRT-D). This pilot will establish the rates of enrollment, randomization, and retention of older patients to guide the design of a pivotal trial. If the pivotal trial supports our hypothesis that CRT-P is non-inferior to CRT-D, this finding would lead to changes in current CRT guidelines and clinical practice, ultimately leading to improved patient outcomes and significant reduction to the cost of heart failure management.
