Endovascular Ablation of the Greater Splanchnic Nerve in Heart Failure With Preserved Ejection Fraction: The REBALANCE-HF Randomized Clinical Trial

IMPORTANCE: Greater splanchnic nerve ablation may improve hemodynamics in patients with heart failure and preserved ejection fraction (HFpEF). OBJECTIVE: To explore the feasibility and safety of endovascular right-sided splanchnic nerve ablation for volume management (SAVM). DESIGN, SETTING, AND PARTICIPANTS: This was a phase 2, double-blind, 1:1, sham-controlled, multicenter, randomized clinical trial conducted at 14 centers in the US and 1 center in the Republic of Georgia. Patients with HFpEF, left ventricular ejection fraction of 40% or greater, and invasively measured peak exercise pulmonary capillary wedge pressure (PCWP) of 25 mm Hg or greater were included. Study data were analyzed from May 2023 to June 2024. INTERVENTION: SAVM vs sham control procedure. MAIN OUTCOMES AND MEASURES: The primary efficacy end point was a reduction in legs-up and exercise PCWP at 1 month. The primary safety end point was serious device- or procedure-related adverse events at 1 month. Secondary efficacy end points included HF hospitalizations, changes in exercise function and health status through 12 months, and baseline to 1-month change in resting, legs-up, and 20-W exercise PCWP. RESULTS: A total of 90 patients (median [range] age, 71 [47-90] years; 58 female [64.4%]) were randomized at 15 centers (44 SAVM vs 46 sham). There were no differences in adverse events between groups. The primary efficacy end point did not differ between SAVM or sham (mean between-group difference in PCWP, −0.03 mm Hg; 95% CI, −2.5 to 2.5 mm Hg; P = .95). There were also no differences in the secondary efficacy end points. There was no difference in the primary safety end point between the treatment (6.8% [3 of 44]) and sham (2.2% [1 of 46]) groups (difference, 4.6%; 95% CI, −6.1% to 15.4%; P = .36). There was no difference in the incidence of orthostatic hypotension between the treatment (11.4% [5 of 44]) and sham (6.5% [3 of 46]) groups (difference, 4.9%; 95% CI, −9.2% to 18.8%; P = .48). CONCLUSIONS AND RELEVANCE: Results show that SAVM was safe and technically feasible, but it did not reduce exercise PCWP at 1 month or improve clinical outcomes at 12 months in a broad population of patients with HFpEF. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04592445