Pulmonary artery denervation shows promise for group I PAH patients, JACC study.

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.

In this regard, the results of a randomised sham-controlled published recently in JACC CI, have shown that in patients with WHO Group I PAH, PADN improved exercise capacity, hemodynamics and clinical outcomes during 6-month follow-up.

While advances in medical therapies have improved symptom control and clinical outcomes, patients with PAH have a poor long-term prognosis. A hyperactive sympathetic nervous system has been implicated in PAH.

In an early human study PADN reduced pulmonary arterial pressures and improved exercise capacity during 3-month follow-up. A subsequent study demonstrated improved hemodynamics, exercise performance, and cardiac function 1-year after PADN. Authors Zhang et al therefore performed a multicenter, randomized, single-blind trial to evaluate the safety and effectiveness of PADN in PAH.

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.

1. Among 128 randomized patients, those treated with PADN compared with sham had a greater improvement in 6MWD from baseline to 6.

2. 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. PADN also improved right ventricular function, reduced tricuspid regurgitation and decreased NT-proBNP.

3. Clinical worsening was less and a satisfactory clinical response was with PADN treatment during 6-month follow-up.

No major complications occurred from the PADN procedure, similar to previous studies. The incremental improvement in 6MWD with PADN (median 33.8 m) in patients on the background PDE-5i treatment was at least as good as in prior trials in which a second PAH-specific drug was added to monotherapy, or a third drug was added to combination therapy.

Since follow-up for only 6 months is available at present, hence longer-term assessments (planned for 3 years) are essential to examine the durability of the present outcomes.

To summarize, in the present sham-controlled, single-blind randomized trial of stable patients with PAH, treatment with PADN plus a PDE-5i was safe and resulted in improved exercise capacity at 6 months compared with background therapy of PDE-5itreatment alone.

Source: JACC CI: DOI: 10.1016/j.jcin.2022.09.013