Mechanistic Basis for Differential Effects of Interatrial Shunt Treatment in HFrEF vs HFpEF: The RELIEVE-HF Trial
- PMID: 40892630
- DOI: 10.1016/j.jcmg.2025.08.005
Mechanistic Basis for Differential Effects of Interatrial Shunt Treatment in HFrEF vs HFpEF: The RELIEVE-HF Trial
Abstract
Background: The RELIEVE-HF (REducing Lung congestion symptoms using the v-wavE shunt in adVancEd Heart Failure) trial randomized 508 patients with heart failure (HF) to interatrial shunt treatment vs placebo procedure. Randomization was stratified into 2 patient groups: heart failure with reduced ejection fraction (HFrEF) (left ventricular ejection fraction [LVEF] ≤40%); and heart failure with preserved ejection fraction (HFpEF) (LVEF >40%). HF event rates (all-cause death, transplantation or left ventricular (LV) assist device, HF hospitalization or outpatient worsening) after shunt treatment during 2-year follow-up were directionally opposite: decreased by 51% in HFrEF, increased by 69% in HFpEF.
Objectives: This study aims to examine differences in cardiac structure and function before and after interatrial shunt placement in patients with HFrEF vs HFpEF that could underlie these discordant clinical outcomes.
Methods: Serial changes from baseline to 12 months in 17 transthoracic echocardiographic parameters in shunt-treated vs control patients in HFrEF vs HFpEF were assessed and compared by ANCOVA (analysis of covariance).
Results: In shunt-treated vs control patients with HFrEF, there were reductions in median LV end-diastolic volumes (-11.9 mL/m2 [Q1-Q3: -21.3 to -2.5 mL/m2]; P = 0.01) and LV end-systolic volumes (-8.9 mL/m2 [Q1-Q3: -17.2 to -20.7 mL/m2]; P = 0.01) indicative of reverse LV remodeling. There were no significant changes in right ventricular (RV), right atrial, or inferior vena cava sizes or pulmonary artery systolic pressure (PASP). In contrast, shunt-treated vs control patients with HFpEF did not have LV remodeling, but they had increased RV, right atrial, and inferior vena cava dimensions, and PASP also increased (4.7 mm Hg [Q1-Q3: 0.9-8.5 mm Hg]; P = 0.02). LV and RV diastolic compliance were decreased in HFpEF vs HFrEF at baseline and decreased further after shunt treatment in HFpEF.
Conclusions: Differential changes in left-sided and right-sided heart remodeling and PASP following interatrial shunt placement in patients with HFrEF vs HFpEF provide a mechanistic basis for the variable effects on clinical outcomes observed in RELIEVE-HF. (REducing Lung congestion symptoms using the v-wavE shunt in adVancEd Heart Failure [RELIEVE-HF]; NCT03499236).
Keywords: echocardiography; heart failure; interatrial shunt.
Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Funding Support and Author Disclosures This work received funding from V-Wave. Dr Zile has received consulting contracts for advisory committees with Abbott, Adona Medical, Alleviant, Aria CV, Avery Therapeutics, Bayer, CVRx, Diasol, EBR, Edwards Lifesciences, Lilly, GenKardia, Innoventrics, Medtronic, Novartis, Pulnovo, Salubris Biotherapeutics, Sonata, sRNAlytics; V-Wave, Vectorious, and WhiteSwell; and his employer, Medical University of South Carolina, has received funding for enrollment in trials for V-Wave and Corvia. Dr Abraham has received honoraria from Impulse Dynamics, Edwards Lifesciences, and Abbott; has received consulting fees from Zoll Respicardia; is an employee of V-Wave, a subsidiary of Johnson and Johnson Medtech; has held a patent for Mobile Ultrawideband Radar for Monitoring Thoracic Fluid Levels and Cardio-Respiratory Function (publication number: 20210290074); has participated on advisory boards or data safety and monitoring boards for Sensible Medical, WhiteSwell, AquaPass, Cordio Medical, and Boehringer Ingelheim; and his institution has received a grant from the National Institutes of Health (1 UG3/UH3 HL140144-01, August 1, 2018 to July 31, 2024, LOFT-HF). Dr Lindenfeld has received consulting fees from Abbott, Alleviant, Axon, AstraZeneca, Boston Scientific, CVRx, Merck Sharp and Dohme, Medtronic, Edwards Lifesciences, V-Wave, WhiteSwell, Vascular Dynamics, and Bayer. Dr Anker has served as a consultant to Abbott Vascular, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Brahms, Cardiac Dimensions, Cardior, Cordia, CVRx, Cytokinetics, Edwards Lifesciences, Faraday Pharmaceuticals, GlaxoSmithKline, HeartKinetics, Impulse Dynamics (USA), Novartis, Occlutech, Pfizer, Regeneron, Repairon, Sensible Medical Innovations, Servier, V-Wave, Vectorious, and Vifor; has held 2 patent applications regarding MR-proANP through Brahms; and his employer, Charité University Medicine Berlin, has received grants from Vifor (International). Dr Rodés-Cabau has received grants from V-Wave, Edwards Lifesciences, Medtronic, and Boston Scientific; has received consulting fees from V-Wave, Edwards Lifesciences, and Medtronic; has received payment for presentations from Edwards Lifesciences and Medtronic; and his employer has received funding for enrollment in clinical trials for V-Wave. Dr Pfeiffer has received honoraria from Abbott Cardiovascular and Ancora Heart; and his employer, The Penn State University and The Milton S. Hershey Medical Center, has received funding from V-Wave for serving as the echocardiographic core laboratory. Dr Boehmer has received honoraria from Boston Scientific, Impulse Dynamics, Medtronic, Cordio Medical, Kestra Medical Technologies, and BiVACOR; and his employer, The Penn State University and The Milton S. Hershey Medical Center, has received funding from V-Wave for serving as the echocardiographic core laboratory. Dr Litwin has received consulting fees from Corvia Medical, Axon, Alleviant, Lilly, and Novo Nordisk. Dr Núñez has received personal fees from or has served on advisory boards for Alleviant, AstraZeneca, Boehringer Ingelheim, Bayer, Novartis, Novo Nordisk, Pfizer, Rovi, and Vifor Pharma. Dr Lee has served as a consultant for Alleviant Medical. Dr Holcomb has received support for preparation of this manuscript and consulting fees from V-Wave; and has received support for meeting attendance. Dr Eigler is an employee of and has patents issued and planned pending for V-Wave, a subsidiary of Johnson and Johnson Medtech. Dr O’Keefe is an employee of Pentara. Dr Stone has received speaker honoraria from Medtronic, Amgen, Boehringer Ingelheim; has served as a consultant to Robocath, Daiichi-Sankyo, Vectorious, Miracor, Apollo Therapeutics, Cardiac Success, Occlutech, Millennia Biopharma, Ablative Solutions, Oxitope, Elixir, Impulse Dynamics, Asceneuron, Myochron, Remote Cardiac Enablement, Valfix, Zoll, HeartFlow, Shockwave, Adona Medical, Abbott, HighLife, Elucid Bio, Aria, Alleviant, FBR Medical, Colibri, Bioventrix, and MedHub; has equity in or options from Cardiac Success, Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Valfix, and Xenter; and his employer, Mount Sinai Hospital, has received research grants from Shockwave, Biosense Webster, Bioventrix, Abbott, Abiomed, Cardiovascular Systems, Philips, Vascular Dynamics, Pulnovo, V-wave, and the Patient-Centered Outcomes Research Institute (through Weill Cornell Medical Center). Dr Baicu has reported that he has no relationships relevant to the contents of this paper to disclose.
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