ATLANTA – An interatrial shunt was safe but did not reduce heart failure (HF) symptoms compared to a placebo procedure through 2 years in patients with HF, regardless of their ejection fraction level, new randomized trial results show. Gregg W. Stone, MD, of Mount Sinai Hospital, New York, presented these findings Saturday during a Late-Breaking Clinical Trials session at the American College of Cardiology Scientific Sessions 2024. An interatrial shunt may provide an autoregulatory way to lower left atrial pressure and improve HF symptoms and prognosis. Pilot studies demonstrated the ability of the Ventura interatrial shunt (V-Wave Ltd.) to reduce filling pressures, improve cardiac structure and function, relieve symptoms and improve function in patients with heart failure with reduced rejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Therefore, the RELIEVE-HF trial evaluated the safety and effectiveness of the Ventura device in patients with symptomatic HF and any left ventricular ejection fraction (LVEF). Randomization was stratified to HFrEF (LVEF ≤40%) and HFpEF (LVEF ≥40%). The study was funded by V-Wave Medical. The device is delivered over the wire via a retrievable 14-French system. It consists of a nitinol frame with full expanded polytetrafluoroethylene encapsulation and an hourglass shape with a 5.1 mm orifice. Patients implanted with the device undergo dual antiplatelet therapy for 6 months. The primary effectiveness endpoint was the hierarchical composite ranking of all-cause mortality, cardiac transplantation left ventricular assist device (LVAD) implantation, all HF hospitalizations, all outpatient worsening HF events, and change in Kansas City Cardiomyopathy Questionnaire – Overall Score (KCCQ-OS) from baseline to 12 months (with a 5-point minimum difference prespecified). The endpoint was analyzed the Finkelstein-Schoenfeld method, when the last enrolled patient reaches 12 months with the longest follow-up to 24 months, expressed as a win ratio. The primary safety endpoint was device- or procedure-related major adverse events, defined as the composite of all-cause mortality, stroke, systemic embolism or the need for open cardiac surgery or major endovascular surgical repair, at 30 days in the shunt group compared to a prespecified rate of 11%. The trial randomized 508 patients at 94 sites globally between October 2018 and October 2019, 250 to receive the shunt and 258 to a placebo procedure. Median follow-up was 22 months (interquartile range: 13.3-23.9) At baseline, the patients’ mean age was approximately 73 years, and most (about 62%) were male. Median procedure time was 80 minutes in the shunt group and 43 minutes in the placebo group, fluoroscopy time was 14 minutes in the shunt group and 4 minutes in the placebo group, and neither group received contrast. The primary safety endpoint occurred in no patients at 30 days. The upper one-sided 97.5% confidence interval (CI) was 1.5%, which was significantly below the prespecified 11% performance goal (p<0.0001), and no endpoint events had occurred in any shunt patients through 2-year follow-up. The primary effectiveness endpoint, however, did not achieve statistical significance, as the unweighted win ratio was 0.89 (95% CI: 0.72-1.09) and the interim analysis phase-weighted win ratio was 0.86 (95% CI: 0.61-1.22; p=0.20). There was also no significant difference between groups in change in KCCQ-OS (shunt: 9.4 ± 21.6 vs. placebo: 10.2 ± 21.3, p=0.74). This improvement in KCCQ-OS score surprised investigators. “There was a tremendous placebo effect,” Stone said in a news release. “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.” However, the shunt did show a lower risk for HF events in patients with HFrEF (49% vs. 88.6%; relative rate ratio: 0.55; 95% CI: 0.42-0.73, p<0.0001), and showed a higher risk for HF events in patients with HFpEF (60.2% vs. 35.9%; relative rate ratio: 1.68; 95% CI: 1.29-2.19; p=0.0001), with a significant interaction between LVEF group levels (p-interaction < 0.0001). Despite this difference in the stratified LVEF groups’ results, one limitation the study investigators listed is that the study is not powered for effectiveness in these groups. Stone concluded that the study suggests the interatrial shunt implantation is beneficial in HFrEF patients and harmful in HFpEF patients. Photo Credit: Jason Wermers/CRTonline.org Photo Caption: Gregg W. Stone, MD, presents results of the RELIEVE-HF trial Saturday at ACC.24 in Atlanta.