One-Year Safety and Clinical Outcomes of a Transcatheter Interatrial Shunt Device for the Treatment of Heart Failure With Preserved Ejection Fraction in the Reduce Elevated Left Atrial Pressure in Patients With Heart Failure (REDUCE LAP-HF I) Trial: A Randomized Clinical Trial

Abstract

Importance: In patients with heart failure (HF) and left ventricular ejection fraction (LVEF) equal to or greater than 40%, a transcatheter interatrial shunt device (IASD; Corvia Medical) reduces exercise pulmonary capillary wedge pressure (PCWP) and is safe compared with sham control treatment at 1 month of follow-up. The longer-term safety and patency of the IASD has not yet been demonstrated in the setting of a randomized clinical trial (RCT).

Objective: To evaluate the 1-year safety and clinical outcomes of the IASD compared with a sham control treatment.

Design, setting, and participants: This phase 2, double-blind, 1-to-1 sham-controlled multicenter RCT of IASD implantation vs a sham procedure (femoral venous access and imaging of the interatrial septum without IASD) was conducted in 22 centers in the United States, Europe, and Australia on patients with New York Heart Association (NYHA) class III or ambulatory class IV HF, LVEF equal to or greater than 40%, exercise PCWP equal to or greater than 25 mm Hg, and PCWP-right atrial pressure gradient equal to or greater than 5 mm Hg.

Main outcomes and measures: Safety was assessed by major adverse cardiac, cerebrovascular, or renal events (MACCRE). Exploratory outcomes evaluated at 1 year were hospitalizations for HF, NYHA class, quality of life, a 6-minute walk test, and device patency.

Results: After 1 year, shunts were patent in all IASD-treated patients; MACCRE did not differ significantly in the IASD arm (2 of 21 [9.5%]) vs the control arm (5 of 22 [22.7%]; P = .41), and no strokes occurred. The yearly rate of hospitalizations for HF was 0.22 in the IASD arm and 0.63 in the control arm (P = .06). Median improvement in NYHA class was 1 class in the IASD arm (IQR, -1 to 0) vs 0 in the control arm (IQR, -1 to 0; P = .08). Quality of life and 6-minute walk test distance were similar in both groups. At 6 months, there was an increase in right ventricular size in the IASD arm (mean [SD], 7.9 [8.0] mL/m2) vs the control arm (-1.8 [9.6] mL/m2; P = .002), consistent with left-to-right shunting through the device; no further increase occurred in the IASD arm at 12 months.

Conclusions and relevance: The REDUCE LAP-HF I phase 2, sham-controlled RCT confirms the longer-term patency of the IASD. Through 1 year of follow-up, IASD treatment appears safe, with no significant differences in MACCRE in patients receiving IASD compared with those who received sham control treatment.

Trial registration: ClinicalTrials.gov identifier: NCT02600234.

Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Burkhoff reports receiving personal fees from Corvia Medical Inc, outside of the submitted work. Dr Chetcuti reports personal fees and grants from Medtronic, personal fees from Boston Scientific and JENA, and grants from Edwards and Biotrace. Dr Cleland reports nonfinancial support from Corvia Medical Inc during the conduct of the study and grants and personal fees from Novartis outside the submitted work. Dr Feldman reports grants from Corvia Medical Inc during the conduct of the study and grants and personal fees from Abbott, BSC, Edwards, and Gore outside the submitted work. Dr Herrmann reports grants from Corvia Medical Inc during the conduct of the study. Dr Hummel reports serving as a trial site principal investigator for Corvia Medical Inc during the conduct of the study, as well as for Pfizer, Novartis, and AstraZeneca; he also reports receiving grants from PurFoods, LLC. Dr Massaro reports that he is a paid statistical consultant for Corvia Medical Inc and has been paid for some analyses presented in this article. Dr Mauri reports that she is advisory board member, a clinical trial design committee member, and executive committee chairperson for Corvia Medical Inc during the conduct of this study; she has also received grants and personal fees from Amgen, Boehringer Ingleheim, and Recor and grants from Biotronik, Boston Scientific, and Svelte outside the submitted work. Dr Shah reports receiving funding from the National Institutes of Health (grants R01 HL127028 and R01 HL 107577), Actelion, AstraZeneca, Corvia Medical Inc, and Novartis and receiving consulting fees from Actelion, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Cardiora, Eisai, Ironwood, Merck, Novartis, Pfizer, Sanofi, and United Therapeutics. Dr Walton reports receiving grants and personal fees from Medtronic and Abbott. No other disclosures were reported.

Figures

Figure 1.. Study Participant Disposition Flowchart at 12 Months

Figure 2.. Cumulative 12-Month Incidence of Major Adverse Cardiac, Cerebrovascular, and Renal Events and Heart Failure Events Requiring Intravenous Diuretic Treatment, Stratified by Treatment Group

MACCRE indicates major adverse cardiac, cerebrovascular, and renal events.

Figure 3.. Change in New York Heart Association Functional Class, Stratified by Study Arm