Interatrial shunt for HF: neutral primary endpoint but potential benefit in HFrEF

In its composite primary efficacy outcome, the RELIEVE-HF trial did not observe a benefit for an interatrial shunt device in the overall cohort of patients with heart failure (HF). However, further stratified analysis showed a potential benefit in patients with reduced left ventricular ejection fraction (HFrEF) and potential harm for those with preserved EF (HFpEF).

Increased left atrial pressure can be difficult to control with medication [1]. Hence, the rationale for the multicentre, double-blind, sham-controlled RELIEVE-HF trial (NCT03499236) was to explore whether the implantation of an interatrial shunt would be effective for patients with either HFrEF or HFpEF [1]. The 508 participants were randomised to receive a V-Wave® Ventura® shunt or a placebo procedure. To enable differentiation of results according to the type of HF, randomisation was stratified according to reduced EF (≤40%) and preserved EF (>40%).

The effectiveness up to 2 years was assessed by a hierarchical composite of all-cause death, heart transplant or left ventricular assist device (LVAD), recurrent HF hospitalisations, out-patient worsening HF events, and change in Kansas City Cardiomyopathy Questionnaire Overall Summary Scores (KCCQ-OSS). The results on each level were reported in wins and losses for the trial arms.

RELIEVE-HF did not meet this primary efficacy endpoint as no significant difference was found for the win ratio between groups (P=0.20). Similar results were found for the risk of all cardiovascular (CV) events and KCCQ-OSS. “Where the results became particularly informative, is when we looked at the stratified randomisations according to EF,” Prof. Gregg Stone (Icahn School of Medicine at Mount Sinai, NY, USA) highlighted.

Participants with HFrEF randomised to the shunt arm had a CV event rate of 49% per year compared with 88.6% in the placebo group (relative rate ratio 0.55; 95% CI 0.42–0.73; P<0.0001). “In patients with HFpEF the exact opposite pattern was seen,” revealed Prof. Stone. Their control-arm event rate was 35.9%, while this was 60.2% in the shunt group (relative rate ratio 1.68; 95% CI 1.29–2.19; P=0.0001). The risk of all CV events showed directionally consistent trends for benefit and harm at stratification. Of note, the change in quality-of-life did not differ between the strata, pointing to a relevant placebo effect in KCCQ-OSS outcomes.

Safety in terms of any device-related or procedure-related major adverse cardiac or neurologic events was not observed in any of the 250 participants with a shunt at 30 days and through 2 years.

1. Stone G, et al. A Double-blind, Randomized Placebo Procedure-controlled Trial of an Interatrial Shunt in Patients with HFrEF and HFpEF: Principal Results from the RELIEVE-HF Trial. LB1, Session 402, ACC 2024 Scientific Session, 6–8 April, Atlanta, USA.

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Posted on 16 May 202413 June 2024