Endovascular Ablation of the Right Greater Splanchnic Nerve in Heart Failure With Preserved Ejection Fraction: Rationale, Design and Lead-in Phase Results of the REBALANCE-HF Trial.

OBJECTIVE: Splanchnic vasoconstriction augments transfer of blood volume from the abdomen into the thorax, which may increase filling pressures and hemodynamic congestion in patients with noncompliant hearts. Therapeutic interruption of splanchnic nerve activity holds promise to reduce hemodynamic congestion in patients with heart failure with preserved ejection fraction (HFpEF). Here we describe (1) the rationale and design of the first sham-controlled, randomized clinical trial of splanchnic nerve ablation for HFpEF and (2) the 12-month results of the lead-in (open-label) trial's participants. METHODS: REBALANCE-HF is a prospective, multicenter, randomized, double-blinded, sham-controlled clinical trial of endovascular, transcatheter, right-sided greater splanchnic nerve ablation for volume management (SAVM) in patients with HFpEF. The primary objectives are to evaluate the safety and efficacy of SAVM and identify responder characteristics to inform future studies. The trial consists of an open-label lead-in phase followed by the randomized, sham-controlled phase. The primary efficacy endpoint is the reduction in pulmonary capillary wedge pressure (PCWP) at 1-month follow-up compared to baseline during passive leg raise and 20W exercise. Secondary and exploratory endpoints include health status (Kansas City Cardiomyopathy Questionnaire), 6-minute walk test distance, New York Heart Association class, and NTproBNP levels at 3, 6 and 12 months. The primary safety endpoint is device- or procedure-related serious adverse events at the 1-month follow-up. RESULTS: The lead-in phase of the study, which enrolled 26 patients with HFpEF who underwent SAVM, demonstrated favorable safety outcomes and reduction in exercise PCWP at 1 month post-procedure and improvements in all secondary endpoints at 6 and 12 months of follow-up. The randomized phase of the trial (n = 44 SAVM; n = 46 sham) has completed enrollment, and follow-up is ongoing. CONCLUSION: REBALANCE-HF is the first sham-controlled randomized clinical trial of greater splanchnic nerve ablation in HFpEF. Initial 12-month open-label results are promising, and the results of the randomized portion of the trial will inform the design of a future pivotal clinical trial. SAVM may offer a promising therapeutic option for patients with HFpEF. TRIAL REGISTRATION: NCT04592445.

Endovascular Ablation of the Greater Splanchnic Nerve in Heart Failure With Preserved Ejection Fraction: The REBALANCE-HF Randomized Clinical Trial.

Importance: Greater splanchnic nerve ablation may improve hemodynamics in patients with heart failure and preserved ejection fraction (HFpEF). Objective: To explore the feasibility and safety of endovascular right-sided splanchnic nerve ablation for volume management (SAVM). Design, Setting, and Participants: This was a phase 2, double-blind, 1:1, sham-controlled, multicenter, randomized clinical trial conducted at 14 centers in the US and 1 center in the Republic of Georgia. Patients with HFpEF, left ventricular ejection fraction of 40% or greater, and invasively measured peak exercise pulmonary capillary wedge pressure (PCWP) of 25 mm Hg or greater were included. Study data were analyzed from May 2023 to June 2024. Intervention: SAVM vs sham control procedure. Main Outcomes and Measures: The primary efficacy end point was a reduction in legs-up and exercise PCWP at 1 month. The primary safety end point was serious device- or procedure-related adverse events at 1 month. Secondary efficacy end points included HF hospitalizations, changes in exercise function and health status through 12 months, and baseline to 1-month change in resting, legs-up, and 20-W exercise PCWP. Results: A total of 90 patients (median [range] age, 71 [47-90] years; 58 female [64.4%]) were randomized at 15 centers (44 SAVM vs 46 sham). There were no differences in adverse events between groups. The primary efficacy end point did not differ between SAVM or sham (mean between-group difference in PCWP, -0.03 mm Hg; 95% CI, -2.5 to 2.5 mm Hg; P = .95). There were also no differences in the secondary efficacy end points. There was no difference in the primary safety end point between the treatment (6.8% [3 of 44]) and sham (2.2% [1 of 46]) groups (difference, 4.6%; 95% CI, -6.1% to 15.4%; P = .36). There was no difference in the incidence of orthostatic hypotension between the treatment (11.4% [5 of 44]) and sham (6.5% [3 of 46]) groups (difference, 4.9%; 95% CI, -9.2% to 18.8%; P = .48). Conclusions and Relevance: Results show that SAVM was safe and technically feasible, but it did not reduce exercise PCWP at 1 month or improve clinical outcomes at 12 months in a broad population of patients with HFpEF. Trial Registration: ClinicalTrials.gov Identifier: NCT04592445.

Early safety and feasibility of a first-in-class biomimetic transcatheter aortic valve - DurAVR.

BACKGROUND: TAVI is a widely accepted treatment for patients with severe aortic stenosis (AS). Despite the adoption of diverse therapies, opportunities remain to develop technologies tailored to provide optimal acute and potential long-term benefits, particularly around haemodynamics, flow and durability. AIMS: We aimed to evaluate the safety and feasibility of the DurAVR transcatheter heart valve (THV), a first-in-class biomimetic valve, in the treatment of patients with symptomatic severe AS. METHODS: This was a first-in-human (FIH), prospective, non-randomised, single-arm, single-centre study. Patients with severe, symptomatic AS of any surgical risk and who were eligible for the DurAVR THV prosthesis were recruited; they were assessed at baseline, 30 days, 6 months, and 1 year post-procedure for implant success, haemodynamic performance, and safety. RESULTS: Thirteen patients (73.9±6.4 years old, 77% female) were enrolled. The DurAVR THV was successfully implanted in 100% of cases with no device-related complications. One access site complication, one permanent pacemaker implantation, and one case of moderate aortic regurgitation occurred. Otherwise, no deaths, stroke, bleeding, reinterventions, or myocardial infarction were reported during any of the follow-up visits. Despite a mean annulus size of 22.95±1.09 mm, favourable haemodynamic results were observed at 30 days (effective orifice area [EOA] 2.00±0.17 cm2, and mean pressure gradient [MPG] 9.02±2.68 mmHg) and were sustained at 1 year (EOA 1.96±0.11 cm2, MPG 8.82±1.38 mmHg), resulting in zero patients with any degree of prosthesis-patient mismatch. Additionally, new valve performance measures derived from cardiovascular magnetic resonance displayed restoration of laminar flow, consistent with a predisease state, in conjunction with a mean coaptation length of 8.3±1.7 mm. CONCLUSIONS: Preliminary results from the FIH study with DurAVR THV demonstrate a good safety profile with promising haemodynamic performance sustained at 1 year and restoration of near-normal flow dynamics. Further clinical investigation is warranted to evaluate how DurAVR THV may play a role in addressing the challenge of lifetime management in AS patients.

Transvenous Right Greater Splanchnic Nerve Ablation in Heart Failure and Preserved Ejection Fraction: First-in-Human Study.

BACKGROUND: Ablation of the right-sided greater splanchnic nerve (GSN) can reduce excessive splanchnic vasoconstriction, potentially improving the handling of volume shifts in patients with heart failure with preserved ejection fraction (HFpEF). OBJECTIVES: The purpose of this study was to assess a novel catheter procedure of right-sided GSN ablation to treat HFpEF: splanchnic ablation for volume management. METHODS: This trial included 11 HFpEF patients (8 women, age 70 ± 8 years) with New York Heart Association functional class II or III symptoms, ejection fraction ≥50%, and elevated pulmonary capillary wedge pressure at rest or with exercise. After splanchnic ablation for volume management, follow-up at 1, 3, 6, and 12 months included 6-minute walk test, Kansas City Cardiomyopathy Questionnaire (KCCQ), and echocardiography. RESULTS: There were no device-related adverse cardiac events or clinical sequelae following right GSN ablation through 12 months. Patients experienced clinical improvements by 1 month that were sustained through 12 months. KCCQ score improved from baseline median 48 (IQR: 35-52) to 65 (IQR: 58-77) at 1 month and 80 (IQR: 77-88) at 12 months (P < 0.05). The 6-minute walk test distance increased from baseline 292 ± 82 m to 341 ± 88 m at 1 month and 359 ± 75 m at 12 months (P < 0.05). The NT-proBNP decreased from a baseline mean of 1,292 ± 1,186 pg/mL to 1,202 ± 797 pg/mL (P = 0.585) at 1 month, to 472 ± 226 pg/mL (P = 0.028) at 6 months, and to 379 ± 165 pg/mL (P = 0.039) at 12 months. CONCLUSIONS: In this open-label, single-arm feasibility study, right-sided GSN ablation was safe and improved mostly subjective clinical metrics in patients with HFpEF over 12 months. (Endovascular GSN Ablation in Subjects With HFpEF; NCT04287946).