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Clinical Trial
. 2024 Dec 1;9(12):1143-1153.
doi: 10.1001/jamacardio.2024.2612.

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

Marat Fudim  1   2   3 , Barry A Borlaug  4 , Rajeev C Mohan  5 , Matthew J Price  5 , Peter Fail  6 , Parag Goyal  7 , Scott L Hummel  8 , Teona Zirakashvili  9   10 , Tamaz Shaburishvili  9 , Ravi B Patel  11 , Vivek Y Reddy  12 , Christopher D Nielsen  13 , Stanley J Chetcuti  8 , Devraj Sukul  8 , Rajiv Gulati  4 , Luke Kim  7 , Keith Benzuly  11 , Sumeet S Mitter  14 , Liviu Klein  15 , Nir Uriel  16 , Ralph S Augostini  17 , John E Blair  18 , Krishna Rocha-Singh  19 , Daniel Burkhoff  20 , Manesh R Patel  1   2 , Sami I Somo  21 , Sheldon E Litwin  13 , Sanjiv J Shah  11
Affiliations
Clinical Trial

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

Marat Fudim et al. JAMA Cardiol. .

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Fudim reported receiving research funding from Bodyport and Sardocor and consulting fees or having ownership interest in Abbott, Ajax, Alio Health, Alleviant, Artha, Audicor, AxonTherapies, Bayer, Bodyguide, Bodyport, Boston Scientific, Broadview, Cadence, Cardioflow, Coridea, CVRx, Daxor, Deerfield Catalyst, Edwards LifeSciences, and Echosens outside the submitted work. Dr Borlaug reported receiving research grant funding from AstraZeneca, Axon, GlaxoSmithKline, Medtronic, Mesoblast, Novo Nordisk, and Tenax Therapeutics; serving as a consultant for Actelion, Amgen, Aria, BD, Boehringer Ingelheim, Cytokinetics, Edwards Lifesciences, Eli Lilly, Janssen, Merck, and Novo Nordisk; being an inventor (US Patent no. 10,307,179) for the tools and approach for a minimally invasive pericardial modification procedure to treat heart failure; and receiving funding from EKO, Feldschuh Foundation, Fire1, FutureCardia, Galvani, Gradient, Hatteras, HemodynamiQ, Impulse Dynamics, Intershunt, Medtronic, Merck, NIMedical, NovoNordisk, NucleusRx, NXT Biomedical, Orchestra, Pharmacosmos, PreHealth, Presidio, Procyreon, ReCor, Rockley, SCPharma, Shifamed, Splendo, Summacor, SyMap, Verily, Vironix, Viscardia, and Zoll outside the submitted work. Dr Mohan reported receiving consulting and/or research fees to institution from Corvia, Alleviant Medical, Pfizer, Bristol Myers Squibb, and AstraZeneca; research funds paid to the institution from Axon Therapies, Corvia, Alleviant Medical and V-Wave; and having equity interest in HemodynamiQ. Dr Price reported receiving consulting fees from Abbott, Boston Scientific, Medtronic, Shockwave, Alleviant Medical, WL Gore, InnovHeart, and Philips Medical and having equity interest in InterShunt. Dr Fail reported receiving nonfinancial support from Corvia and Allvient Medical outside the submitted work. Dr Goyal reported receiving consulting fees from Akros Pharma, Agepha Pharma, Axon Therapies, and Sensorum Health outside the submitted work. Dr Hummel reported serving as site principal investigator for Corvia Medical, Alleviant Medical, and Novo Nordisk and receiving grants from Veterans Health Administration, National Institutes of Health, Agency for Healthcare Research and Quality, and University of Michigan outside the submitted work. Dr Reddy reported serving as a consultant for and receiving stock options from Axon Therapies during the conduct of the study and serving as a consultant for and having equity in Ablacon, Acutus Medical, Affera-Medtronic, Apama Medical-Boston Scientific, Anumana, APN Health, Aquaheart, Atacor, Autonomix, Backbeat, BioSig, CardiaCare, CardioNXT / AFTx, Circa Scientific, CoRISMA, Corvia Medical, Dinova-Hangzhou DiNovA EP Technology, East End Medical, EPD-Philips, EP Frontiers, Epix Therapeutics-Medtronic, EpiEP, Eximo, Farapulse-Boston Scientific, Field Medical, Focused Therapeutics, HRT, Intershunt, Javelin, Kardium, Keystone Heart, Laminar Medical, LuxMed, Medlumics, Middlepeak, Neutrace, Nuvera-Biosense Webster, Oracle Health, Restore Medical, Sirona Medical, SoundCath, Valcare; unrelated to this work, has served as a consultant for Abbott, Adagio Medical, AtriAN, Biosense-Webster, BioTel Heart, Biotronik, Boston Scientific, Cairdac, Cardiofocus, Cardionomic, CoreMap, Fire1, Gore & Associates, Impulse Dynamics, Medtronic, Novartis, Philips, Pulse Biosciences; and has equity in DRS Vascular, Manual Surgical Sciences, Newpace, Nyra Medical, Surecor, and Vizaramed outside the submitted work. Dr Chetcuti reported receiving consultant fees from MDT, Edwards Life Sciences, and BSCI. Dr Kim reported receiving consultant fees from Axon Therapies and grant support from Abbott and Medtronic during the conduct of the study. Dr Mitter reported receiving advisory board fees from Alnyalm, Pfizer, Bridge Bio, and AstraZeneca outside the submitted work. Dr Klein reported receiving grants from University of California at San Francisco during the conduct of the study. Dr Uriel reported receiving grants from Abbott and Abiomed and advisory board fees from Livemetric, Leviticus, and Revamp Medical outside the submitted work. Dr Burkhoff reported receiving consultant fees and grant support from Axon Medical to Cardiovascular Research Foundation. Dr M. Patel reported receiving grants from Bayer, Janssen, Novartis, and the National Heart, Lung, and Blood Institute and personal fees from Bayer during the conduct of the study. Dr Somo reported being employed by Axon Therapies. Dr Litwin reported receiving research support or consulting fees from Axon, Corvia, Eli Lilly, AstraZeneca, Alleviant, V-Wave, and Novo Nordisk outside the submitted work. Dr Shah reported receiving consulting fees from Abbott, Alleviant, Amgen, Aria CV, AstraZeneca, Axon Therapies, Bayer, Boehringer Ingelheim, Boston Scientific, BridgeBio, Bristol Myers Squibb, Corvia, Cytokinetics, Edwards Lifesciences, Eidos, Imara, Impulse Dynamics, Intellia, Ionis, Lilly, Merck, NGM Biopharmaceuticals, Novartis, Novo Nordisk, Pfizer, Prothena, Regeneron, Rivus, Sardocor, Shifamed, Tenax, Tenaya, and Ultromics outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Participant Flow Diagram
The flow diagram describes the disposition of all patients screened in the Endovascular Ablation of the Right Greater Splanchnic Nerve in Subjects Having Heart Failure With Preserved Ejection Fraction: Feasibility Study (REBALANCE-HF) study. Ninety patients were randomized with 44 and 46 in the active treatment (splanchnic nerve ablation) and sham control groups, respectively. The modified intention-to-treat (mITT) group included 89 patients (1 patient in the active treatment group was excluded due to treatment failure).
Figure 2.
Figure 2.. Primary Efficacy End Point in the Modified Intention-to-Treat (mITT) Analysis
Baseline and 1-month exercise pulmonary capillary wedge pressure (PCWP) for the mITT study cohort. A, Splanchnic ablation for volume management (SAVM) group. B, Sham group. The primary efficacy end point was a reduction in PCWP at legs-up and 20-W exercise. The values represent mean, and the error bars indicate SD. There was no difference between treatment and sham for legs-up and 20-W exercise PCWP. LS indicates least squares.
See this image and copyright information in PMC

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