RELIEVE-HF Evaluates V-Wave’s Ventura Interatrial Shunt by Heart Failure Type

April 6, 2024—RELIEVE-HF is a randomized, placebo-procedure–controlled trial that evaluated interatrial shunting. The study included patients with both major types of heart failure: heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF).

The evaluated device was the Ventura interatrial shunt from V-Wave Medical, which sponsored RELIEVE-HF. Ventura is designed to form a small connection or passage between the left and right atria to allow blood to leave the left atrium—especially as left atrial pressure rises—thus reducing the pressure in the left atrium and the lungs.

Findings from RELIEVE-HF were presented by Gregg Stone, MD, at ACC.24, the American College of Cardiology’s Annual Scientific Session held April 6-8 in Atlanta, Georgia.

According to ACC, the investigators reported that patients with heart failure who received the shunt inserted between the heart’s left and right atria did not see any significant benefits overall compared with those patients who received a placebo procedure after a median of 22 months of follow-up.

The investigators noted that although the trial did not meet its primary endpoint, it moves the field forward by offering signals that the benefits and risks of interatrial shunts may vary by heart failure type.

“When you examine the outcomes in patients with heart failure across a broad range of left ventricular ejection fraction, the Ventura interatrial shunt was extremely safe but did not improve outcomes compared with no treatment,” commented Dr. Stone in the ACC press release. “However, in a prespecified analysis, data suggest that the shunt may be beneficial in patients with HFrEF and worsen outcomes in patients with HFpEF. We believe further studies are warranted to confirm the benefits we observed in patients with reduced ejection fraction.”

As summarized in the ACC press release, the trial randomized 508 patients at 94 sites in North America, Europe, Israel, Australia, and New Zealand. All patients in the study had symptomatic heart failure despite taking medications at maximally tolerated doses. Approximately 40% of participants had HFrEF and 60% had HFpEF.

The patients were randomly assigned to undergo a procedure to insert the Ventura shunt or a placebo procedure in which a script was followed with all the same protocols to mask patients as to whether the shunt was inserted. Operators were aware of which procedure each patient received but patients, the patients’ families, and the rest of the medical teams taking care of the patient after the procedure were not aware.

The RELIEVE-HF investigators tracked outcomes in each patient for at least 1 year and up to 2 years.

ACC press release advised that the results showed no significant difference between groups in terms of the trial’s primary endpoint.

The primary endpoint was a hierarchical composite ranking of death from any cause; heart transplant or left ventricular assist device; heart failure hospitalizations; worsening of outpatient heart failure events; and change in quality of life, as measured using the Kansas City Cardiomyopathy Questionnaire (KCCQ). This hierarchical composite approach for assessing efficacy allows diverse types of outcomes to be incorporated in ranked fashion into an overall “win ratio” reflecting the overall outcome of a drug or device, noted ACC.

In a preplanned analysis focused on heart failure type, patients with HFrEF who received the shunt were found to have improvements across all outcomes assessed (especially fewer hospitalizations for heart failure). Patients with HFpEF who received the shunt were found to have increased rates of death and heart failure hospitalizations.

The press release noted that Dr. Stone said that this difference could be attributed to the greater compliance or flexibility of the heart muscle with HFrEF, potentially allowing it to more easily accommodate the extra blood flowing into the right atrium.

There were no device-related or procedure-related major adverse cardiovascular or neurologic events in either group during the duration of the trial.

Notably, the study showed a marked improvement in quality of life as measured with KCCQ that was observed across all groups, including those who received a placebo procedure, both with HFrEF and HFpEF. This suggests that the metric may not be a reliable indicator for quality-of-life outcomes in this context, stated Stone.

Dr. Stone added, “There was a tremendous placebo effect. These observations, especially the fact that quality of life improved in HFpEF patients who were more likely to be hospitalized for heart failure and had reduced survival after shunt treatment, raise questions about the interpretation of this quality-of-life measure in these kinds of trials.”

Although the observed differences in outcomes among people with different types of heart failure may inform future research and development for interatrial devices, the investigators said that the trial was not powered to show differences in the two types of heart failure. As such, these results should be considered exploratory. They also said that the results may not be applicable to other interatrial shunts beyond the Ventura shunt, advised the ACC press release.