Pulmonary Artery Denervation for Pulmonary Arterial Hypertension: A Sham-Controlled Randomized PADN-CFDA Trial

Abstract

Background: World Health Organization (WHO) group 1 pulmonary arterial hypertension (PAH) is a progressive, debilitating disease. Previous observational studies have demonstrated that pulmonary artery denervation (PADN) reduces pulmonary artery pressures in PAH. However, the safety and effectiveness of PADN have not been established in a randomized trial.

Objectives: The aim of this study was to determine the treatment effects of PADN in patients with group 1 PAH.

Methods: Patients with WHO group 1 PAH not taking PAH-specific drugs for at least 30 days were enrolled in a multicenter, sham-controlled, single-blind, randomized trial. Patients were assigned to receive PADN plus a phosphodiesterase-5 inhibitor or a sham procedure plus a phosphodiesterase-5 inhibitor. The primary endpoint was the between-group difference in the change in 6-minute walk distance from baseline to 6 months.

Results: Among 128 randomized patients, those treated with PADN compared with sham had a greater improvement in 6-minute walk distance from baseline to 6 months (mean adjusted between-group difference 33.8 m; 95% CI: 16.7-50.9 m; P < 0.001). From baseline to 6 months, pulmonary vascular resistance was reduced by -3.0 ± 0.3 WU after PADN and -1.9 ± 0.3 WU after sham (adjusted difference -1.4; 95% CI: -2.6 to -0.2). PADN also improved right ventricular function, reduced tricuspid regurgitation, and decreased N-terminal pro-brain natriuretic peptide. Clinical worsening was less (1.6% vs 13.8%; OR: 0.11; 95% CI: 0.01-0.87), and a satisfactory clinical response was greater (57.1% vs 32.3%; OR: 2.79; 95% CI: 1.37-5.82) with PADN treatment during 6-month follow-up.

Conclusions: In patients with WHO group 1 PAH, PADN improved exercise capacity, hemodynamic status, and clinical outcomes during 6-month follow-up. (Safety and Efficacy of Pulmonary Artery Denervation in Patients With Pulmonary Arterial Hypertension [PADN-CFDA]; NCT03282266).

Keywords: 6-minute walk distance; pulmonary arterial hypertension; pulmonary artery denervation; pulmonary artery pressure; pulmonary vascular resistance.

Conflict of interest statement

Funding Support and Author Disclosures This trial was supported by the National Scientific Foundation of China (grants NSFC 91639303, and NSFC 81770441, and NSFC 82121001). Nanjing First Hospital funded this trial, and Pulnovo Medical provided all PADN catheters through the study period. Dr Stone has received speaker honoraria from Medtronic, Pulnovo Medical, and Infraredx; has served as a consultant to Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Abiomed, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Vascular Dynamics, Shockwave, V-Wave, Cardiomech, Gore, and Amgen; and has equity or options in Ancora, Cagent, Applied Therapeutics, the Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter. Dr Stone’s daughter is an employee at Medtronic. Dr Stone’s employer, Mount Sinai Hospital, has received research support from Abbott, Abiomed, Bioventrix, Cardiovascular Systems, Phillips, Biosense Webster, Shockwave, Vascular Dynamics, and V-Wave. Dr S.-L. Chen is the inventor of PADN but not the owner of the PADN patent; has received speaker honoraria from Microport, Pulnovo Medical, Boston Scientific, Medtronic, Sanofi, and BioMed; is a fellow at the Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University; and has received grants from the National Scientific Foundation of China. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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