The RAISE Trial: A Novel Device and First-in-Man Trial

Abstract

Background: Currently, standard medical therapies have limited effects on heart failure with preserved ejection fraction (HFpEF), which impacts on the life quality and survival of patients. This study aimed to evaluate the safety and efficacy of the percutaneous radiofrequency ablation–based interatrial shunting for HFpEF with a novel atrial septostomy device. Methods: A preclinical study in 11 normal domestic pigs and the first-in-man study in 10 patients with HFpEF were performed. The major safety events and interatrial shunt performance were evaluated at baseline, 1 month, 3 months, and 6 months post-procedure in both animals and human patients. The clinical functional status was also assessed in the first-in-man study. Results: Percutaneous radiofrequency ablation–based interatrial shunting therapy was performed successfully both in animals and patients. In the animal study, a left-to-right interatrial shunt was created with a mean defect size of 5.5±2.2 mm without procedure-related safety events. Seven pigs showed the continuous shunting with a mean defect size of 4.1±1.5 mm at 6 months. In the first-in-man study, a median interatrial defect diameter of 5.0 (4.0–6.0) mm was measured immediately. No major safety events including death and thromboembolism were observed. The continuous shunting with the defect size of 4.0 (3.0–4.0) mm could still be observed in 7 patients at 6 months. The clinical status was significantly improved with NT-proBNP (N-terminal pro-B-type natriuretic peptide) reduced by 2149 pg/mL ([95% CI, 204–3301] P =0.028), with 6-minute walk distance increased by 88 m ([95% CI, 50–249] P =0.008) and with New York Heart Association class improved in 8 patients at 6 months. Conclusions: The present results showed that percutaneous radiofrequency ablation–based interatrial shunting was a safe and potentially effective therapy for HFpEF, providing a nonpharmacological and nonimplanted option for HFpEF management. Registration: URL: https://www.chictr.org.cn ; Unique identifier: ChiCTR1900027664.