Endovascular Ablation of the Right Greater Splanchnic Nerve for the Treatment of Heart Failure with Preserved Ejection Fraction - First-in-human Clinical Trial

Abstract

Background In HFpEF, increased sympathetic outflow to the splanchnic venous system causes chronic redistribution of blood volume into the central circulation, which leads to exercise limitations, hemodynamic deterioration, and worsening outcomes. We have previously shown that surgical right greater splanchnic nerve (GSN) ablation in HFpEF leads to a reduction of PCWP, improved quality of life and exercise capacity. Objective Demonstrate feasibility of a novel transvenous approach to right-sided GSN ablation for the treatment of HFpEF. Methods In a non-randomized, open-label trial, 11 HFpEF patients (3 male, 8 female, 70±8 years) with NYHA class II/III, LVEF ≥ 50% and high baseline PCWP at rest or with exercise, underwent right GSN ablation with the Axon Transvenous GSN Ablation System. Follow-up assessments (1 and 3 months) include the 6MWT, KCCQ, blood labs, and echocardiography. Change from baseline ablation to each follow-up were compared using paired Wilcoxon rank-sum tests. Data shown as mean ± standard deviation, unless otherwise noted. Results Two procedure related events were reported in 2 patients prior to the 1-month timepoint: bradycardia due to anesthesia and acute decrease in eGFR of >20 ml/min/1.73 m2, both of which returned to baseline without sequelae. Expected AEs related to the catheterization procedure were observed and resolved without sequalae, including access site hematoma (1), access site pain (1), right intercostal pain (1). There were no device related adverse cardiac events and no unanticipated adverse device effects. Efficacy results (Table) demonstrate marked improvements and/or favorable trends in quality of life (NYHA and KCCQ), exercise capacity (6MWT), diastolic function (E/e’ ratio) and HF severity (NTproBNP). Although the study was underpowered to show a statistically significant improvement in 6MWT from baseline, there was a clinically relevant improvement in distance compared to baseline of at least 30 m in all patients at 1 and 3 months, and at least a 45 m in 5/11 patients at 1 month and 8/11 patients at 3 months. Conclusion These results demonstrate, for the first time ever, the feasibility of treating HFpEF with endovascular right-sided GSN ablation. The encouraging safety and efficacy results provide rationale for a phase 2 randomized controlled trial.