RELIEVE-HF Trial: Interatrial Shunt Safe but Ineffective for Heart Failure, Yields Mixed Results by Ejection Fraction

While the study, published in the journal Circulation, found that the procedure was safe, it did not result in improved overall outcomes for patients with heart failure. However, a closer look at a prespecified exploratory analysis indicates that the treatment may provide benefits for specific patient groups.

"Findings from a prespecified exploratory analysis of stratified randomized groups indicate that shunt implantation may be advantageous for patients with reduced left ventricular ejection fraction (LVEF), while it appears harmful for those with preserved LVEF," the researchers wrote.

An interatrial shunt could offer an autoregulatory mechanism to lower left atrial pressure, potentially enhancing symptoms and outcomes in HF. Considering this, Gregg W. Stone, The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY, and colleagues included patients with symptomatic HF with any LVEF.

Participants were randomized in a 1:1 ratio to receive either transcatheter shunt implantation or a placebo procedure, with stratification based on left ventricular ejection fraction (LVEF): reduced (≤40%) versus preserved (>40%). The primary safety outcome was a composite of major adverse cardiovascular or neurological events related to the device or procedure within 30 days, compared against a prespecified performance goal of 11%.

The primary effectiveness outcome was assessed using a hierarchical composite ranking that included all-cause mortality, cardiac transplantation or left ventricular assist device implantation, heart failure hospitalization, outpatient worsening heart failure events, and changes in quality of life as measured by the Kansas City Cardiomyopathy Questionnaire overall summary score over a maximum follow-up of 2 years. This assessment was conducted when the last enrolled patient completed their 1-year follow-up, and results were expressed as a win ratio. Prespecified hypothesis-generating analyses were also conducted for patients with reduced and preserved LVEF.

The following were the main findings of the study:

• Between 2018, and 2022, 508 patients were randomized at 94 sites in 11 countries to interatrial shunt treatment (n=250) or a placebo procedure (n=258).
• The median (25th and 75th percentiles) age was 73.0 years (66.0, 79.0), and 37.2% were women.
• Median LVEF was reduced (≤40%) in 40.6% of the patients and preserved (>40%) in 59.4%.
• No primary safety events occurred after shunt implantation.
• There was no difference in the 2-year primary effectiveness outcome between the shunt and placebo procedure groups (win ratio, 0.86).
• 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), whereas patients with preserved LVEF had more cardiovascular events with shunt treatment (annualized rate 60.2% versus 35.9%; relative risk, 1.68).
• There were no between-group differences in change in the Kansas City Cardiomyopathy Questionnaire overall summary score during follow-up in all patients or those with reduced or preserved LVEF.

Based on the findings, the researchers concluded that transcatheter interatrial shunt implantation was safe; however, it did not improve outcomes for heart failure patients. However, they added that a closer look at a prespecified exploratory analysis indicates that the treatment may benefit specific patient groups.

Reference:

Stone GW, Lindenfeld J, Rodés-Cabau J, Anker SD, Zile MR, Kar S, Holcomb R, Pfeiffer MP, Bayes-Genis A, Bax JJ, Bank AJ, Costanzo MR, Verheye S, Roguin A, Filippatos G, Núñez J, Lee EC, Laufer-Perl M, Moravsky G, Litwin SE, Prihadi E, Gada H, Chung ES, Price MJ, Thohan V, Schewel D, Kumar S, Kische S, Shah KS, Donovan DJ, Zhang Y, Eigler NL, Abraham WT; RELIEVE-HF Investigators. Interatrial Shunt Treatment for Heart Failure: The Randomized RELIEVE-HF Trial. Circulation. 2024 Sep 23. doi: 10.1161/CIRCULATIONAHA.124.070870. Epub ahead of print. PMID: 39308371.