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

Objectives: We aimed to determine the treatment effects of PADN in Group I PAH patients.

Methods: WHO Group I PAH patients 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 (PDE-5i) or a sham procedure plus a PDE-5i. The primary endpoint was the between-group difference in the change in 6-minute walk distance (6MWD) from baseline to 6 months.

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

Conclusions: In patients with WHO Group I PAH, PADN improved exercise capacity, hemodynamics and clinical outcomes during 6-month follow-up. (ClinicalTrials.gov number: NCT03282266).