e-Article
Atrial Shunt Device Effects on Cardiac Structure and Function in Heart Failure With Preserved Ejection Fraction: The REDUCE LAP-HF II Randomized Clinical Trial.
Document Type
Academic Journal
Author
Patel RB; Bluhm Cardiovascular Institute, Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.; Silvestry FE; Division of Cardiovascular Medicine, University of Pennsylvania, Philadelphia.; Komtebedde J; Corvia Medical Inc, Tewksbury, Massachusetts.; Solomon SD; Division of Cardiology, Brigham and Women's Hospital, Boston, Massachusetts.; Hasenfuß G; Heart Centre, Georg-August Universitat, Gottigen, Germany.; Litwin SE; Medical University of South Carolina and Ralph H. Johnson Veterans Affairs Medical Center, Charleston.; Borlaug BA; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota.; Price MJ; Division of Cardiology, Scripps Clinic, La Jolla, California.; Kawash R; Division of Cardiology, Ohio State Wexner Medical Center, Columbus.; Hummel SL; Division of Cardiovascular Medicine, University of Michigan, Ann Arbor.; VA Ann Arbor, Ann Arbor, Michigan.; Cutlip DE; Division of Cardiology, Beth Israel Medical Center, Boston, Massachusetts.; Leon MB; Cardiovascular Research Foundation, New York, New York.; van Veldhuisen DJ; Department of Cardiology, University Medical Center, University of Groningen, Groningen, the Netherlands.; Rieth AJ; Department of Cardiology, Kerckhoff-Klinik, Bad Nauheim, Germany.; German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt am Main, Germany.; McKenzie S; The Prince Charles Hospital, School of Medicine, University of Queensland, Brisbane, Queensland, Australia.; Bugger H; Division of Cardiology, Medical University of Graz, Graz, Austria.; Mazurek JA; Division of Cardiology, Hospital of the University of Pennsylvania, Philadelphia.; Kapadia SR; Division of Cardiology, Cleveland Clinic, Cleveland, Ohio.; Vanderheyden M; Cardiovascular Center Aalst, OLV Hospital, Aalst, Belgium.; Ky B; Division of Cardiovascular Medicine, University of Pennsylvania, Philadelphia.; Shah SJ; Bluhm Cardiovascular Institute, Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Source
Publisher: American Medical Association Country of Publication: United States NLM ID: 101676033 Publication Model: Print Cited Medium: Internet ISSN: 2380-6591 (Electronic) NLM ISO Abbreviation: JAMA Cardiol Subsets: MEDLINE
Subject
Language
English
Abstract
Importance: Although the results of A Study to Evaluate the Corvia Medical Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients with Heart Failure (REDUCE LAP-HF II) trial were neutral overall, atrial shunt therapy demonstrated potential efficacy in responders (no latent pulmonary vascular disease and no cardiac rhythm management device). Post hoc analyses were conducted to evaluate the effect of shunt vs sham stratified by responder status.
Objective: To evaluate the effect of atrial shunt vs sham control on cardiac structure/function in the overall study and stratified by responder status.
Design, Setting, and Participants: This was a sham-controlled randomized clinical trial of an atrial shunt device in heart failure with preserved ejection fraction (HFpEF)/HF with mildly reduced EF (HFmrEF). Trial participants with evaluable echocardiography scans were recruited from 89 international medical centers. Data were analyzed from April 2023 to January 2024.
Interventions: Atrial shunt device or sham control.
Main Outcome Measures: Changes in echocardiographic measures from baseline to 1, 6, 12, and 24 months after index procedure.
Results: The modified intention-to-treat analysis of the REDUCE LAP-HF II trial included 621 randomized patients (median [IQR] age, 72.0 [66.0-77.0] years; 382 female [61.5%]; shunt arm, 309 [49.8%]; sham control arm, 312 [50.2%]). Through 24 months, 212 of 217 patients (98%) in the shunt arm with evaluable echocardiograms had patent shunts. In the overall trial population, the shunt reduced left ventricular (LV) end-diastolic volume (mean difference, -5.65 mL; P <.001), left atrial (LA) minimal volume (mean difference, -2.8 mL; P =.01), and improved LV systolic tissue Doppler velocity (mean difference, 0.69 cm/s; P <.001) and LA emptying fraction (mean difference, 1.88 percentage units; P =.02) compared with sham. Shunt treatment also increased right ventricular (RV; mean difference, 9.58 mL; P <.001) and right atrial (RA; mean difference, 9.71 mL; P <.001) volumes but had no effect on RV systolic function, pulmonary artery pressure, or RA pressure compared with sham. In the shunt arm, responders had smaller increases in RV end-diastolic volume (mean difference, 5.71 mL vs 15.18 mL; interaction P =.01), RV end-systolic volume (mean difference, 1.58 mL vs 7.89 mL; interaction P =.002), and RV/LV ratio (mean difference, 0.07 vs 0.20; interaction P <.001) and larger increases in transmitral A wave velocity (mean difference, 5.08 cm/s vs -1.97 cm/s; interaction P =.02) compared with nonresponders randomized to the shunt, suggesting greater ability to accommodate shunted blood through the pulmonary circulation enabling LA unloading.
Conclusions and Relevance: In this post hoc analysis of the REDUCE LAP-HF II trial, over 2 years of follow-up, atrial shunting led to reverse remodeling of left-sided chambers and increases in volume of right-sided chambers consistent with the shunt flow but no change in RV systolic function compared with sham. Changes in cardiac structure/function were more favorable in responders compared with nonresponders treated with the shunt, supporting the previously identified responder group hypothesis and mechanism, although further evaluation with longer follow-up is needed.
Trial Registration: ClinicalTrials.gov Identifier: NCT03088033.
Objective: To evaluate the effect of atrial shunt vs sham control on cardiac structure/function in the overall study and stratified by responder status.
Design, Setting, and Participants: This was a sham-controlled randomized clinical trial of an atrial shunt device in heart failure with preserved ejection fraction (HFpEF)/HF with mildly reduced EF (HFmrEF). Trial participants with evaluable echocardiography scans were recruited from 89 international medical centers. Data were analyzed from April 2023 to January 2024.
Interventions: Atrial shunt device or sham control.
Main Outcome Measures: Changes in echocardiographic measures from baseline to 1, 6, 12, and 24 months after index procedure.
Results: The modified intention-to-treat analysis of the REDUCE LAP-HF II trial included 621 randomized patients (median [IQR] age, 72.0 [66.0-77.0] years; 382 female [61.5%]; shunt arm, 309 [49.8%]; sham control arm, 312 [50.2%]). Through 24 months, 212 of 217 patients (98%) in the shunt arm with evaluable echocardiograms had patent shunts. In the overall trial population, the shunt reduced left ventricular (LV) end-diastolic volume (mean difference, -5.65 mL; P <.001), left atrial (LA) minimal volume (mean difference, -2.8 mL; P =.01), and improved LV systolic tissue Doppler velocity (mean difference, 0.69 cm/s; P <.001) and LA emptying fraction (mean difference, 1.88 percentage units; P =.02) compared with sham. Shunt treatment also increased right ventricular (RV; mean difference, 9.58 mL; P <.001) and right atrial (RA; mean difference, 9.71 mL; P <.001) volumes but had no effect on RV systolic function, pulmonary artery pressure, or RA pressure compared with sham. In the shunt arm, responders had smaller increases in RV end-diastolic volume (mean difference, 5.71 mL vs 15.18 mL; interaction P =.01), RV end-systolic volume (mean difference, 1.58 mL vs 7.89 mL; interaction P =.002), and RV/LV ratio (mean difference, 0.07 vs 0.20; interaction P <.001) and larger increases in transmitral A wave velocity (mean difference, 5.08 cm/s vs -1.97 cm/s; interaction P =.02) compared with nonresponders randomized to the shunt, suggesting greater ability to accommodate shunted blood through the pulmonary circulation enabling LA unloading.
Conclusions and Relevance: In this post hoc analysis of the REDUCE LAP-HF II trial, over 2 years of follow-up, atrial shunting led to reverse remodeling of left-sided chambers and increases in volume of right-sided chambers consistent with the shunt flow but no change in RV systolic function compared with sham. Changes in cardiac structure/function were more favorable in responders compared with nonresponders treated with the shunt, supporting the previously identified responder group hypothesis and mechanism, although further evaluation with longer follow-up is needed.
Trial Registration: ClinicalTrials.gov Identifier: NCT03088033.