Pacing in Patients With Heart Failure and a QRS Complex >120 Milliseconds"We thank Drs Van Gelder and Bracke for their interest in our study 1 and for raising thoughtful points of discussion.Indeed, Evaluation of Resynchronization Therapy for Heart Failure (GREATER-EARTH)'s randomized and blinded crossover design provided a unique opportunity to assess whether those who did not respond to one strategy did benefit from the alternative strategy.To our knowledge, ours is the first study to report that some who did not respond to biventricular pacing respond favorably when crossed over to left ventricular pacing.This provocative observation currently is being explored to elucidate pathophysiological mechanisms and associated clinical features.Interestingly, Gage et al 2 since have reported consistent findings and likewise have suggested that left ventricular-only pacing may be considered in patients who do not respond to conventional biventricular cardiac resynchronization therapy.In the absence of clear evidence-based recommendations or a widely accepted general consensus, optimal programming for cardiac resynchronization therapy remains controversial and the subject of ongoing research.Within this context, Drs Van Gelder and Bracke hypothesize that a different programming algorithm that includes a longer atrioventricular delay adjusted during exercise and, perhaps most contentiously, ventriculo-ventricular optimization, may have yielded different results.Our data cannot confirm or refute this speculation.The important studies cited by Drs Van Gelder and Bracke, published well after the initiation of GREATER-EARTH, generate hypotheses by demonstrating associations between atrioventricular delays and surrogate outcomes (ie, echocardiographic and hemodynamic parameters).The relevance of these findings with respect to clinical outcomes remains to be demonstrated.The comments by Drs Van Gelder and Bracke underscore the importance of rigorously testing hypotheses, including specific programming schemes, in well-designed clinical trials.Nevertheless, it is worth noting that 2 recent meta-analyses that included studies with a variety of nonuniform programming methods consistently concluded that, on the whole, left ventricular-only pacing is not superior to biventricular pacing. 3,