Strategic Management to Optimize Response to Cardiac Resynchronization Therapy

WIRB will be the Main IRB and Penn will be the relying IRB. NYHA Class I-II patients are now eligible for CRT following the MADIT CRT study, and there are no prior data for these patients using the SmartDelay feature. Furthermore, in the intervening seven years since the SMART AV trial results were first published, there have been changes in technology. Quadripolar leads are available and in use today rather than the unipolar/bipolar leads previously available. Potential changes in implant technique (optimizing lead position for position rather than electrical performance) as well as potential changes in the practice of medicine when treating heart failure patients. Accordingly, a randomized controlled trial was chosen. This study design helps assure that two comparable patient populations are obtained while mitigating bias such that any observed changes are due to the use of SmartDelay alone. The parameters for the study design were taken from the predicate SMART AV study. The SMART AV study was designed to detect a decrease in LVESV of at least 15mL. The SMART CRT study is designed to detect a decrease in LVESV of at least 15%. The modification in the response definition for SMART CRT was made to represent a more appropriate clinical definition of CRT response. Increasing values of RV-LV were associated with an increased effect size. The cutoff value of 70 ms was chosen because it maximized the potential yield of screened patients while still preserving a clinically important effect size. New studies based on previous retrospective analyses may not precisely duplicate the magnitude of effect originally reported. Accordingly, this study was designed to detect at least 75% of the effect size to conserve a clinically meaningful proportion of the effect observed in SMART AV.