The restoration of chronotropic competence in heart failure patients with normal ejection fraction (RESET) study: rationale and design

Abstract

Background: Heart failure with preserved ejection fraction (HFpEF) is the predominant form of heart failure among the elderly and in women. However, there are few if any evidence-based therapeutic options for HFpEF. The chief complaint of HFpEF is reduced tolerance to physical exertion. Recent data revealed that 1 potential mechanism of exertional intolerance in HFpEF patients is inadequate chronotropic response. Although there is considerable evidence demonstrating the benefits of rate-adaptive pacing (RAP) provided from implantable cardiac devices in patients with an impaired chronotropic response, the effect of RAP in HFpEF is unknown.

Methods and results: The Restoration of Chronotropic CompEtence in Heart Failure PatientS with Normal Ejection FracTion (RESET) study is a prospective, multicenter, double-blind, randomized with stratification, study assessing the effect of RAP on peak oxygen consumption and quality of life. RAP therapy will be evaluated in a crossover paired fashion for each patient within each study stratum. Study strata are based on patient beta-blocker usage at time of enrollment. The study is powered to assess the impact of pacing independently in both strata.

Conclusions: The RESET study seeks to evaluate the potential benefit of RAP in patients with symptomatic mild to moderate HFpEF and chronotropic impairment. Study enrollment began in July 2008.

Figure

RESET Study schema. Patients satisfying the inclusion and exclusion criteria are stratified according to beta-blocker usage then progress to the screening visit for implant eligibility testing. Pacing therapy will be evaluated within each stratum in all implanted patients during the one month visits A and B in a randomized fashion. Upon completion of the one month visits, pacing therapy will be active in all patients in each stratum for the duration of the study. βB + or −, with or without beta-blocker; CPX, cardiopulmonary exercise test; CI, chronotropic incompetence; EF, left ventricular ejection fraction; QoL, quality of life; R, within strata randomized cross-over; mo. = 1, 6, 12 month patient follow-up visits respectively; RAP, rate-adaptive pacing; EoS, end of study.