TY - JOUR
T1 - Endovascular ablation of the right greater splanchnic nerve in heart failure with preserved ejection fraction
T2 - early results of the REBALANCE-HF trial roll-in cohort
AU - Fudim, Marat
AU - Fail, Peter S.
AU - Litwin, Sheldon E.
AU - Shaburishvili, Tamaz
AU - Goyal, Parag
AU - Hummel, Scott L.
AU - Borlaug, Barry A.
AU - Mohan, Rajeev C.
AU - Patel, Ravi B.
AU - Mitter, Sumeet S.
AU - Klein, Liviu
AU - Rocha-Singh, Krishna
AU - Patel, Manesh R.
AU - Reddy, Vivek Y.
AU - Burkhoff, Daniel
AU - Shah, Sanjiv J.
N1 - Funding Information:
Axon Therapies, Inc. Conflict of interest: M.F. was supported by the National Heart, Lung, and Blood Institute (NHLBI) (K23HL151744), the American Heart Association (20IPA35310955), Mario Family Award, Duke Chair's Award, Translating Duke Health Award, Bayer, Bodyport and BTG Specialty Pharmaceuticals. He reports consulting fees from Abbott, Audicor, AxonTherapies, Bodyguide, Bodyport, Boston Scientific, CVRx, Daxor, Edwards LifeSciences, Feldschuh Foundation, Fire1, Gradient, Intershunt, NXT Biomedical, Pharmacosmos, PreHealth, Splendo, Vironix, Viscardia, Zoll. B.A.B. has received research support from R01 HL128526 and U01 HL160226, from the National Institutes of Health (NIH), and W81XWH2210245, from the United States Department of Defense, as well as research grants from AstraZeneca, Axon, GlaxoSmithKline, Medtronic, Mesoblast, Novo Nordisk, and Tenax Therapeutics; has received consulting fees from Actelion, Amgen, Aria, Axon Therapies, BD, Boehringer Ingelheim, Cytokinetics, Edwards Lifesciences, Eli Lilly, Imbria, Janssen, Merck, Novo Nordisk, NGM, NXT, and VADovations; is named inventor on an issued patent (US Patent no. 10307179) for the tools and approach for a minimally invasive pericardial modification procedure to treat heart failure. V.Y.R. reports serving as a consultant to, and holding stock options in, Axon Therapies. In addition, he has other disclosures not related to this manuscript: Consultant – Abbott, Biosense-Webster, BioTel Heart, Biotronik, Boston Scientific, Cardiofocus, Cardionomic, CoreMap, EBR, Fire1, Gore & Associates, Impulse Dynamics, Medtronic, Philips, and Pulse Biosciences; Consultant, Equity – Ablacon, Acutus Medical, Affera, Apama Medical, APN Health, Aquaheart, Atacor, Autonomix, Backbeat, BioSig, Cardiac Implants, CardiaCare, CardioNXT/AFTx, Circa Scientific, Corvia Medical, Dinova-Hangzhou DiNovA EP Technology, East End Medical, EPD, Epix Therapeutics, EpiEP, Eximo, Farapulse, HRT, Intershunt, Javelin Lld, Kardium, Keystone Heart, LuxMed, Medlumics, Middlepeak, Nuvera, Philips, Pulse Biosciences, Restore Medical, Sirona Medical, and Valcare; Equity – Manual Surgical Sciences, Newpace, Surecor, and Vizaramed. D.B. reports consulting fees from Axon Therapies. S.J.S. has received research grants from the National Institutes of Health (U54 HL160273, R01 HL107577, R01 HL127028, R01 HL140731, R01 HL149423), Actelion, AstraZeneca, Corvia, Novartis, and Pfizer; and has received consulting fees from Abbott, Actelion, AstraZeneca, Amgen, Aria CV, Axon Therapies, Bayer, Boehringer-Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardiora, Coridea, CVRx, Cyclerion, Cytokinetics, Edwards Lifesciences, Eidos, Eisai, Imara, Impulse Dynamics, Intellia, Ionis, Ironwood, Lilly, Merck, MyoKardia, Novartis, Novo Nordisk, Pfizer, Prothena, Regeneron, Rivus, Sanofi, Shifamed, Tenax, Tenaya, and United Therapeutics. All other authors have nothing to disclose.
Funding Information:
M.F. was supported by the National Heart, Lung, and Blood Institute (NHLBI) (K23HL151744), the American Heart Association (20IPA35310955), Mario Family Award, Duke Chair's Award, Translating Duke Health Award, Bayer, Bodyport and BTG Specialty Pharmaceuticals. He reports consulting fees from Abbott, Audicor, AxonTherapies, Bodyguide, Bodyport, Boston Scientific, CVRx, Daxor, Edwards LifeSciences, Feldschuh Foundation, Fire1, Gradient, Intershunt, NXT Biomedical, Pharmacosmos, PreHealth, Splendo, Vironix, Viscardia, Zoll. B.A.B. has received research support from R01 HL128526 and U01 HL160226, from the National Institutes of Health (NIH), and W81XWH2210245, from the United States Department of Defense, as well as research grants from AstraZeneca, Axon, GlaxoSmithKline, Medtronic, Mesoblast, Novo Nordisk, and Tenax Therapeutics; has received consulting fees from Actelion, Amgen, Aria, Axon Therapies, BD, Boehringer Ingelheim, Cytokinetics, Edwards Lifesciences, Eli Lilly, Imbria, Janssen, Merck, Novo Nordisk, NGM, NXT, and VADovations; is named inventor on an issued patent (US Patent no. 10307179) for the tools and approach for a minimally invasive pericardial modification procedure to treat heart failure. V.Y.R. reports serving as a consultant to, and holding stock options in, Axon Therapies. In addition, he has other disclosures not related to this manuscript: Consultant – Abbott, Biosense‐Webster, BioTel Heart, Biotronik, Boston Scientific, Cardiofocus, Cardionomic, CoreMap, EBR, Fire1, Gore & Associates, Impulse Dynamics, Medtronic, Philips, and Pulse Biosciences; Consultant, Equity – Ablacon, Acutus Medical, Affera, Apama Medical, APN Health, Aquaheart, Atacor, Autonomix, Backbeat, BioSig, Cardiac Implants, CardiaCare, CardioNXT/AFTx, Circa Scientific, Corvia Medical, Dinova‐Hangzhou DiNovA EP Technology, East End Medical, EPD, Epix Therapeutics, EpiEP, Eximo, Farapulse, HRT, Intershunt, Javelin Lld, Kardium, Keystone Heart, LuxMed, Medlumics, Middlepeak, Nuvera, Philips, Pulse Biosciences, Restore Medical, Sirona Medical, and Valcare; Equity – Manual Surgical Sciences, Newpace, Surecor, and Vizaramed. D.B. reports consulting fees from Axon Therapies. S.J.S. has received research grants from the National Institutes of Health (U54 HL160273, R01 HL107577, R01 HL127028, R01 HL140731, R01 HL149423), Actelion, AstraZeneca, Corvia, Novartis, and Pfizer; and has received consulting fees from Abbott, Actelion, AstraZeneca, Amgen, Aria CV, Axon Therapies, Bayer, Boehringer‐Ingelheim, Boston Scientific, Bristol‐Myers Squibb, Cardiora, Coridea, CVRx, Cyclerion, Cytokinetics, Edwards Lifesciences, Eidos, Eisai, Imara, Impulse Dynamics, Intellia, Ionis, Ironwood, Lilly, Merck, MyoKardia, Novartis, Novo Nordisk, Pfizer, Prothena, Regeneron, Rivus, Sanofi, Shifamed, Tenax, Tenaya, and United Therapeutics. All other authors have nothing to disclose. Conflict of interest:
Publisher Copyright:
© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
PY - 2022/8
Y1 - 2022/8
N2 - Aims: In heart failure (HF) with preserved ejection fraction (HFpEF), excessive redistribution of blood volume into the central circulation leads to elevations of intracardiac pressures with exercise limitations. Splanchnic ablation for volume management (SAVM) has been proposed as a therapeutic intervention. Here we present preliminary safety and efficacy data from the initial roll-in cohort of the REBALANCE-HF trial. Methods and results: The open-label (roll-in) arm of REBALANCE-HF will enrol up to 30 patients, followed by the randomized, sham-controlled portion of the trial (up to 80 additional patients). Patients with HF, left ventricular ejection fraction (LVEF) ≥50%, and invasive peak exercise pulmonary capillary wedge pressure (PCWP) ≥25 mmHg underwent SAVM. Baseline and follow-up assessments included resting and exercise PCWP, New York Heart Association (NYHA) class, Kansas City Cardiomyopathy Questionnaire (KCCQ), 6-min walk test, and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Efficacy and safety were assessed at 1 and 3 months. Here we report on the first 18 patients with HFpEF that have been enrolled into the roll-in, open-label arm of the study across nine centres; 14 (78%) female; 16 (89%) in NYHA class III; and median (interquartile range) age 75.2 (68.4–81) years, LVEF 61.0 (56.0–63.2)%, and average (standard deviation) 20 W exercise PCWP 36.4 (±8.6) mmHg. All 18 patients were successfully treated. Three non-serious moderate device/procedure-related adverse events were reported. At 1-month, the mean PCWP at 20 W exercise decreased from 36.4 (±8.6) to 28.9 (±7.8) mmHg (p < 0.01), NYHA class improved by at least one class in 33% of patients (p = 0.02) and KCCQ score improved by 22.1 points (95% confidence interval 9.4–34.2) (p < 0.01). Conclusion: The preliminary open-label results from the multicentre REBALANCE-HF roll-in cohort support the safety and efficacy of SAVM in HFpEF. The findings require confirmation in the ongoing randomized, sham-controlled portion of the trial.
AB - Aims: In heart failure (HF) with preserved ejection fraction (HFpEF), excessive redistribution of blood volume into the central circulation leads to elevations of intracardiac pressures with exercise limitations. Splanchnic ablation for volume management (SAVM) has been proposed as a therapeutic intervention. Here we present preliminary safety and efficacy data from the initial roll-in cohort of the REBALANCE-HF trial. Methods and results: The open-label (roll-in) arm of REBALANCE-HF will enrol up to 30 patients, followed by the randomized, sham-controlled portion of the trial (up to 80 additional patients). Patients with HF, left ventricular ejection fraction (LVEF) ≥50%, and invasive peak exercise pulmonary capillary wedge pressure (PCWP) ≥25 mmHg underwent SAVM. Baseline and follow-up assessments included resting and exercise PCWP, New York Heart Association (NYHA) class, Kansas City Cardiomyopathy Questionnaire (KCCQ), 6-min walk test, and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Efficacy and safety were assessed at 1 and 3 months. Here we report on the first 18 patients with HFpEF that have been enrolled into the roll-in, open-label arm of the study across nine centres; 14 (78%) female; 16 (89%) in NYHA class III; and median (interquartile range) age 75.2 (68.4–81) years, LVEF 61.0 (56.0–63.2)%, and average (standard deviation) 20 W exercise PCWP 36.4 (±8.6) mmHg. All 18 patients were successfully treated. Three non-serious moderate device/procedure-related adverse events were reported. At 1-month, the mean PCWP at 20 W exercise decreased from 36.4 (±8.6) to 28.9 (±7.8) mmHg (p < 0.01), NYHA class improved by at least one class in 33% of patients (p = 0.02) and KCCQ score improved by 22.1 points (95% confidence interval 9.4–34.2) (p < 0.01). Conclusion: The preliminary open-label results from the multicentre REBALANCE-HF roll-in cohort support the safety and efficacy of SAVM in HFpEF. The findings require confirmation in the ongoing randomized, sham-controlled portion of the trial.
KW - Clinical trial
KW - Heart failure with preserved ejection fraction
KW - Splanchnic nerve ablation
KW - Therapeutics
UR - http://www.scopus.com/inward/record.url?scp=85130889229&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85130889229&partnerID=8YFLogxK
U2 - 10.1002/ejhf.2559
DO - 10.1002/ejhf.2559
M3 - Article
C2 - 35598154
AN - SCOPUS:85130889229
SN - 1388-9842
VL - 24
SP - 1410
EP - 1414
JO - European Journal of Heart Failure
JF - European Journal of Heart Failure
IS - 8
ER -