Heart Failure Study of Multipoint Pacing Effects on Ventriculoarterial Coupling: Rationale and Design of the HUMVEE Trial

Cardiac resynchronization therapy (CRT) is an established therapy for symptomatic heart failure (HF). Unfortunately, many recipients remain nonresponders. Studies have revealed the potential role of multipoint pacing (MPP) in improving response and outcomes. The aim of this study is to compare the effects of MPP against those of standard biventricular pacing (BVP) on (i) ventriculoarterial coupling (VAC) and energy efficiency of the failing heart, (ii) diastolic function, (iii) quality of life, and (iv) NT-proBNP levels and glomerular filtration rate (GFR) during a follow-up of 13 months. HUMVEE is a single-center, prospective, observational, crossover cohort study. Seventy-six patients with BVP indication will be implanted with a system able to deliver both pacing modes. BVP will be activated at implantation and optimized 1 month after. At 6 months postoptimization MPP will be activated and optimized. Optimization will be performed based on stroke volume maximization, as assessed by ultrasound. Laboratory measurements (GFR and NT-proBNP) and echocardiographic studies (VAC calculation, strain rate, diastolic function) will be performed at implantation, 6 months post-BVP optimization and at the end of 13 months of follow-up (6 months post-MPP optimization). Potential reduction in arrhythmogenesis by MPP will also be assessed. MPP is a pacing modality with the potential to improve HF patients' outcomes. The HUMVEE trial will attempt to associate any potential added beneficial effects of MPP over standard BVP with alterations in VAC and energy efficiency of the heart, thus uncovering a novel mechanistic link between MPP and improved outcomes in HF.