Pulmonary artery denervation (PADN) improved exercise capacity, hemodynamics and clinical outcomes in patients with Group I pulmonary arterial hypertension (PAH) as classified by the World Health Organization (WHO), 6-month trial data report.

Findings from the sham-controlled trial led by Hang Zhang, MD, from Nanjing First Hospital of Nanjing Medical University, China, were reported Sunday at Transcatheter Cardiovascular Therapeutics (TCT) 2022 in Boston and published simultaneously online in JACC: Cardiovascular Interventions.

The team noted that while advances in medical therapies have improved symptom control and clinical outcomes, patients with PAH have a poor long-term prognosis. However, previous studies have shown that PADN can reverse experimental balloon-induced pulmonary hypertension and improve pulmonary arterial remodeling and right ventricular function.

In an early human study, PADN reduced pulmonary arterial pressures and improved exercise capacity during 3-month follow-up, the team noted, adding that subsequent research showed improved hemodynamics, exercise performance and cardiac function 1 year after PADN.

“This study clearly demonstrates that treatment with PADN plus a PDE-5i [phosphodiesterase 5 inhibitor] was safe and resulted in improved exercise capacity at six months compared with PDE-5i treatment alone,” said Shao-Liang Chen, MD, PhD, also of Nanjing First Hospital, speaking at TCT 2022. Chen is the senior and corresponding author of the simultaneous publication.

“In addition, we found significant improvements in hemodynamics as well as a reduction in clinical worsening with PADN. Larger randomized trials are needed to demonstrate the incremental benefits of PADN in patients on combination pharmacotherapy.”

Study setup

The trial randomly assigned 128 patients with WHO Group I PAH not taking PAH-specific drugs for at least 30 days to be treated with PADN plus post-procedure titrated medical therapy – PDE-5i – or a sham procedure plus PDE-5i.

Chen noted that between January 2018 and June 2021, 186 PAH patients were screened at 11 centers in China, from which 128 were randomly assigned to the PADN group (n=63) or the sham procedure (n=65). The primary endpoint was the between-group difference in the change in 6-minute walk distance (6MWD) from baseline to 6 months.

Baseline characteristics of the randomized patients revealed a mean age of 40.8 years, while 82.8% were women. PAH etiology was idiopathic in 54.7% of cases, said the researchers.

Furthermore, baseline average 6MWD was 401 m, while mean pulmonary arterial pressure (mPAP) measured by right heart catheterization was 53.9 mmHg, mean pulmonary vascular resistance (PVR) was 10.9 Wood units (WU), and mean N-terminal-pro brain natriuretic peptide (NT-proBNP) level was 2,345 pg/mL.

Key findings

The research team reported that PADN incrementally improved 6MWD, cardiac hemodynamics and function, and provided a satisfactory clinical response from baseline to 6 months in WHO Group I patients treated with background PDE-5i therapy.

Chest pain was reported more commonly in the PADN group, but the pain was mild and did not require analgesia, they said, noting that no major procedural complications occurred in either group.

A PDE-5i was administered to 92% of patients in both groups at 6 months, with comparable use of sildenafil and tadalafil, they added, noting that combination drug therapy was required in three (4.8%) patients in the PADN group and in seven (10.8%) patients in the sham group at 6 months (difference -6.0, 95% CI -17.3 to 5.1).

PADN resulted in a greater improvement in 6MWD from baseline to 6 months (mean adjusted between-group difference 33.8 m, 95% confidence interval [CI], 16.7 to 50.9, p<0.001), said Chen, noting a median change in 6MWD from baseline to 6 months was 61.0 m (interquartile range [IQR]: 12.0 to 92.0) in the PADN group and 18.0 m (IQR: -9.0 to 66.0) in the sham group (p=0.004). These results were similar after post hoc adjustment for age, sex, and body mass index and in a sensitivity analysis using multiple imputations.

Clinical worsening during 6-month follow-up was also reduced (1.6% vs. 13.8%; odds ratio [OR] 0.11; 95% CI 0.01 to 0.87) and a satisfactory clinical response at 6 months was more frequently achieved (57.1% vs. 32.3%; OR 2.79; 95% CI 1.37 to 5.82) by PADN treatment, the team reported. PVR was also reduced from baseline to 6 months by -3.0 WU after PADN and -1.9 WU after sham (adjusted difference -1.4, 95% CI -2.6 to -0.2), while PADN also improved right ventricular function, reduced tricuspid regurgitation and decreased NT-proBNP, they said.

Furthermore, diuretic use was less and was at a lower daily dose after PADN at both 1 and 6 months. Other medications were used with similar frequency in both groups during follow-up.

“In the present multicenter, 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-5i treatment alone,” said the authors of the study. “In addition, treatment with PADN reduced PVR and PAP, improved right ventricular function, reduced tricuspid regurgitation and NT-proBNP levels, and improved clinical outcomes during 6-month follow-up.”

They added that the results should now be replicated in larger studies, and especially in patients with a suboptimal response to combination pharmacotherapy, before widespread application.

Source:

Zhang H, Wei Y, Zhang C, et al. Outcomes After Transcatheter Edge-to-Edge Mitral Valve Repair According to Mitral Regurgitation Etiology and Cardiac Remodeling. JACC Cardiovasc Interv 2022 Sep 18 (Article in press)

Image Credit: Jason Wermers/CRTonline.org