Multicenter Sham-Controlled Randomized Trial of Pulmonary Artery Denervation Shows Promise for Pulmonary Arterial Hypertension
Results Presented at TCT and Published Simultaneously in JACC: Cardiovascular Interventions
BOSTON – September 18, 2022 – A new sham-controlled clinical evaluation of pulmonary artery denervation (PADN) for patients with pulmonary arterial hypertension (PAH) found that in addition to increasing exercise capacity, PADN improved hemodynamics and clinical outcomes during six-month follow-up.
Findings were reported today at TCT 2022, the 34th annual scientific symposium of the Cardiovascular Research Foundation (CRF). TCT is the world’s premier educational meeting specializing in interventional cardiovascular medicine.
PAH is a progressive, debilitating disease characterized by obliterative pulmonary vascular remodeling with elevated pulmonary vascular resistance. Despite advances in medical treatment, PAH is associated with a poor long-term prognosis. Previous observational studies have demonstrated that PADN improves hemodynamic and exercise capacity in patients with PAH but has not yet been studied in a randomized trial.
Between January 2018 and June 2021, 128 PAH patients were randomized to PADN (n=63) or a sham procedure (n=65) at 11 centers in China. Patients not taking PAH-specific drugs for at least 30 days were enrolled. Both PADN and sham procedure patients received a phosphodiesterase-5 inhibitor (PDE-5i). For the sham procedure, the PADN catheter was positioned at the target site but ablation was not performed. Measurement of N-terminal-pro brain natriuretic peptide (NT-proBNP), a six-minute walk test (6MWD), and transthoracic echocardiography were performed at baseline and at days 7, 30, and 180 using standardized procedures.
The primary endpoint was the between-group difference in the change in 6MWD from baseline to six months. The 6MWD improved in both groups during follow-up, with the between-group difference becoming significant by 30 days. The median change from baseline to six months was 61.0 m (12.0 to 92.0) in the PADN group and 18.0 m (-9.0 to 66.0) in the sham group (p=0.004). The adjusted between-group mean difference in the change of 6MWD from baseline to six months was 33.8 m (95% CI, 16.7 to 50.9; p<0.001).
At six 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 also 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.
“This study clearly demonstrates that treatment with PADN plus a PDE-5i was safe and resulted in improved exercise capacity at six months compared with PDE-5i treatment alone,” said Shao-Liang Chen, MD, PhD, Director of Cardiology and Cath Lab, Nanjing First Hospital. Dr. Chen is also Vice President of Nanjing First Hospital, Nanjing Medical University and Professor of Internal Medicine and Cardiology, Nanjing Medical University. “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.”
The study was granted by the National Scientific Foundation of China (grant number NSFC 91639303, NSFC 81770441 and NSFC 82121001). Nanjing First Hospital funded the trial and Pulnovo provided all PADN catheters through the study period.
Dr. Chen reported being the inventor of PADN but not the owner of the PADN patent; speaker honoraria from Microport, Pulnovo, Boston International Scientific, Medtronic, Sinofi, and BioMed; and grants from the National Scientific Foundation of China.
About CRF and TCT
The Cardiovascular Research Foundation (CRF) is one of the world’s leading nonprofit organizations specializing in interventional cardiology innovation, research, and education. CRF is dedicated to helping doctors improve survival and quality of life for people suffering from heart and vascular disease. For over 30 years, CRF has helped accelerate medical breakthroughs and educated doctors on the latest treatments for heart disease. CRF’s centers of excellence include the CRF Skirball Center for Innovation, CRF Clinical Trials Center, CRF Center for Education, CRF Digital, TCTMD, and Structural Heart: The Journal of the Heart Team.
Transcatheter Cardiovascular Therapeutics (TCT) is the annual scientific symposium of CRF and the premier educational meeting specializing in interventional cardiovascular medicine. Now in its 34th year, TCT features major medical research breakthroughs and gathers leading researchers and clinicians from around the world to present and discuss the latest evidence-based research in the field.