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.

Transcatheter interventions for heart failure

“…In the experimental proof of concept, the intervention appeared safe with sustained patency and no thromboembolic or other complications. The first-in-human experience, limited to 10 patients, demonstrated early feasibility and favourable changes in surrogate efficacy parameters; however, shunt narrowing over time was reported in the majority of patients 27 . An additional clinical programme is under development to evaluate the efficacy and safety of this approach in a larger patient population.…”

Device-based percutaneous treatments to decompress the left atrium in heart failure with preserved ejection fraction

“…PCWP was reduced at 100 days (− 9 mmHg;) with diminished LA-to-RA gradients (− 10 mmHg) 2 deaths (20%) during follow-up (one at 221 days and the other at 450 days). No HFH (median follow-up 261 days) Radiofrequency ablation–based interatrial shunt Sun et al, Circulation: Heart Failure (2022) [ 67 ] First-in-man trial n = 10 (90%) HFpEF or HFmrEF with NYHA functional classes II–IV and at least one HFH during the last years though OMT, NT-proBNP > 200 pg/mL (or > 600 if AF) and LAP > 15 mmHg Primary endpoints: SADE and interatrial shunt performance. Secondary endpoints: HFH and the change in clinical functions at 6 months No SADE during the whole study (100%) Shunt could still be observed in 7 patients at 6 months (2 patients showed the closure and 1 patient missed follow-up).…”

“…After ablation, the device was removed from the body, leaving nothing but an artificial ASD [ 59 ]. This novel approach was evaluated first in 11 domestic pigs and then in 9 HFpEF patients and 1 with HFmrEF with NYHA functional classes II–IV [ 67 ]. RAIAS therapy was successfully administered to all patients, and an evidence interatrial left-to-right shunt flow was detected with a mean Qp:Qs of 1.3 ± 0.3.…”

“…Patients showed improvements of NYHA functional class ( p = 0.003) at 6 months, a reduction of median NT-proBNP from 3533 to 1347 pg/mL ( p = 0.028), and an improvement in 6MWD from 349 to 440 m ( p = 0.008). In addition, echocardiographic parameters showed a mean decrease of 3.1 ± 3.9 mm in the LA diameter at 6 months compared with baseline ( p = 0.042), reflecting the reduced overloading of the LA after RAIAS [ 67 ].…”

Update on Atrial Shunt Therapy for Treatment of Heart Failure

“… 28 2019 3 mo HFrEF/HFpEF, NYHA Class −1.4/−1.1; KCCQ ↑16/↑ 20; 6MW ↑ 30/↑ 26 m; PCWP ↓2/↓5 mm Hg; Qp:Qs 1.3/1.1 Occlutech AFR PROLONGER study, AFteR registry Currently enrolling NoYa Pilot Single arm (EF >35%) 10 Lotan 2019 1-3 mo Shunt diameter 3-4 mm; 6MW ↑ 56 m; BNP ↓ 1878 pg/mL NoYa RAISE trial Single arm 10 Sun et al. 29 2022 3/10 shunts closed by 6 mo in pigs; 3/10 shunts closed at 6 mo in humans Alleviant HF-1, HF-2, HFrEF Single arm, 28 HFpEF, 5 HFrEF 33 total Preliminary data presented at THT, TVT and SCAI meetings 2022 7 mm shunt; no implant; 100% patency 6 mo; ↓ ex PCWP; ↑6MW; Ongoing f/u. Edwards Life Sciences ALt FLOW Single arm 15 Recruiting Pivotal trials Corvia REDUCE LAP-HF II Double-blind RCT (EF >40%) 626 Shah et al.…”