Interatrial Shunt Treatment for Heart Failure: The Randomized RELIEVE-HF Trial
Authors: Stone Gregg W. , Lindenfeld JoAnn , Rodés-Cabau Josep , Anker Stefan D. , Zile Michael R. , Kar Saibal , Holcomb Richard , Pfeiffer Michael P. , Bayes-Genis Antoni , Bax Jeroen J. , Bank Alan J. , Costanzo Maria Rosa , Verheye Stefan , Roguin Ariel , Filippatos Gerasimos , Núñez Julio , Lee Elizabeth C. , Laufer-Perl Michal , Moravsky Gil , Litwin Sheldon E. , Prihadi Edgard , Gada Hemal , Chung Eugene S. , Price Matthew J. , Thohan Vinay , Schewel Dimitry , Kumar Sachin , Kische Stephan , Shah Kevin S. , Donovan Daniel J. , Zhang Yiran , Eigler Neal L. , Abraham William T. , Gorcsan John , Kukin Marrick , Bhatt Kunjan , Shavelle David , Klein Liviu , Romero Alicia , Haas Garrie , Swarup Vijay , Volz Elizabeth , Collado Fareed , Badiye Amit , Grazette Luanda , Hamilton Michelle , McRae Tom , Lamba Sumant , Krueger Steven , Byrne Timothy , Miller Leslie , Al-Saghir Youssef , Chand Robin , Shavelle David , Khoury Saeb , Dauber Ira , Mazimba Sula , Mittal Suneet , Driver Steven , Weiner Stanislav , Kapadia Samir , Gosain Priyanka , Singh Rajeev , Krejcer Zvonimir , Punnoose Lynn , Russell Stuart , Karas Maria , Kumar Gautam , Nair Ajith , Widmer Robert , Kundur Ramesh , Dib Nabil , Egolum Ugochukwu , Villela Miguel Alvarez , Boehmer John , Petrossian George , Teuteberg Jeffrey , Bittenbender Peter , Santos Ignacio Amat , Garcia Ana , del Trigo Maria , Mirabet Sònia Pérez , Nombela Luis , Figal Domingo Pascual , Gotsman Israel , Kinany Wadi , Goland Sorel , Freimark Dov , Hasin Tal , Caspi Oren , Lev Eli , Alnsasra Hilmi , Sievers Burkhard , Sherif Mohammad , Fengler Karl , Wachter Rolf , Hüseyin Ince , Hausleiter Jörg , Von Bardeleben Ralf Stephan , Hüseyin Ince , Ibrahim Reda , Horlick Eric , Krakowiak Bartosz , Witkowski Adam , Wojakowski Wojciech , Van Der Heyden Jan , Van Mieghem Nicholas , Post Martijn , DePasquale Carmine , Ruschitzka Frank , Troughton Richard 
Published: September 2024

BACKGROUND:

An interatrial shunt may provide an autoregulatory mechanism to decrease left atrial pressure and improve heart failure (HF) symptoms and prognosis.

METHODS:

Patients with symptomatic HF with any left ventricular ejection fraction (LVEF) were randomized 1:1 to transcatheter shunt implantation versus a placebo procedure, stratified by reduced (≤40%) versus preserved (>40%) LVEF. The primary safety outcome was a composite of device-related or procedure-related major adverse cardiovascular or neurological events at 30 days compared with a prespecified performance goal of 11%. The primary effectiveness outcome was the hierarchical composite ranking of all-cause death, cardiac transplantation or left ventricular assist device implantation, HF hospitalization, outpatient worsening HF events, and change in quality of life from baseline measured by the Kansas City Cardiomyopathy Questionnaire overall summary score through maximum 2-year follow-up, assessed when the last enrolled patient reached 1-year follow-up, expressed as the win ratio. Prespecified hypothesis-generating analyses were performed in patients with reduced and preserved LVEF.

RESULTS:

Between October 24, 2018, and October 19, 2022, 508 patients were randomized at 94 sites in 11 countries to interatrial shunt treatment (n=250) or a placebo procedure (n=258). Median (25th and 75th percentiles) age was 73.0 years (66.0, 79.0), and 189 patients (37.2%) were women. Median LVEF was reduced (≤40%) in 206 patients (40.6%) and preserved (>40%) in 302 patients (59.4%). No primary safety events occurred after shunt implantation (upper 97.5% confidence limit, 1.5%;
P
<0.0001). There was no difference in the 2-year primary effectiveness outcome between the shunt and placebo procedure groups (win ratio, 0.86 [95% CI, 0.61–1.22];
P
=0.20). However, patients with reduced LVEF had fewer adverse cardiovascular events with shunt treatment versus placebo (annualized rate 49.0% versus 88.6%; relative risk, 0.55 [95% CI, 0.42–0.73];
P
<0.0001), whereas patients with preserved LVEF had more cardiovascular events with shunt treatment (annualized rate 60.2% versus 35.9%; relative risk, 1.68 [95% CI, 1.29–2.19];
P
=0.0001;
P
interaction
<0.0001). There were no between-group differences in change in Kansas City Cardiomyopathy Questionnaire overall summary score during follow-up in all patients or in those with reduced or preserved LVEF.

CONCLUSIONS:

Transcatheter interatrial shunt implantation was safe but did not improve outcomes in patients with HF. However, the results from a prespecified exploratory analysis in stratified randomized groups suggest that shunt implantation is beneficial in patients with reduced LVEF and harmful in patients with preserved LVEF.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03499236.