Endovascular Ablation of the Right Greater Splanchnic Nerve in Heart Failure with Preserved Ejection Fraction: Rationale, Design, and Lead-in Phase Results of the REBALANCE-HF Trial

INTRODUCTION:Splanchnic vasoconstriction augments transfer of blood volume from the abdomen into the thorax, which may increase filling pressures and hemodynamic congestion in patients with noncompliant hearts. Therapeutic interruption of splanchnic nerve activity holds promise to reduce hemodynamic congestion in patients with heart failure with preserved ejection fraction (HFpEF). Here we describe (1) the rationale and design of the first sham-controlled randomized clinical trial (RCT) of splanchnic nerve ablation for HFpEF; and (2) the 12-month results of the lead-in (open-label) trial participants. METHODS:REBALANCE-HF is a prospective, multicenter, randomized, double-blinded, sham-controlled clinical trial of endovascular, transcatheter right-sided greater splanchnic nerve ablation for volume management (SAVM) in patients with HFpEF. The primary objectives are to evaluate the safety and efficacy of SAVM and identify responder characteristics to inform future studies. The trial consists of an open-label lead-in phase followed by the randomized, sham-controlled phase. The primary efficacy endpoint is the reduction in pulmonary capillary wedge pressure (PCWP) at 1-month follow-up compared to baseline during passive leg raise and 20W exercise. Secondary and exploratory endpoints include health status (Kansas City Cardiomyopathy Questionnaire), 6-minute walk test distance, New York Heart Association, and NTproBNP at 3, 6, and 12 months. The primary safety endpoint is device- or procedure-related serious adverse events at 1-month follow-up. RESULTS:The lead-in phase of the study, which enrolled 26 HFpEF patients who underwent SAVM, demonstrated favorable safety outcomes and reduction in exercise PCWP at 1-month post-procedure; and improvements in all secondary endpoints at 6 and 12 months of follow-up. The randomized phase of the trial (n=44 SAVM, n=46 sham) has completed enrollment, and follow-up is ongoing. CONCLUSION:REBALANCE-HF is the first sham-controlled RCT of greater splanchnic nerve ablation in HFpEF. Initial 12-month open-label results are promising, and the results of the randomized portion of the trial will inform the design of a future pivotal clinical trial. SAVM may offer a promising therapeutic option for patients with HFpEF. TRIAL REGISTRATION:NCT04592445.