Clinical and Hemodynamic Effects of Pulmonary Artery Denervation in Pulmonary Hypertension Despite Optimized Pharmacotherapy: An Updated Systematic Review and Meta-Analysis

Background: Pulmonary hypertension (PH) remains a progressive and life-threatening condition despite advances in targeted pharmacotherapy. Pulmonary artery denervation (PADN) has emerged as a novel interventional strategy aimed at modulating sympathetic overactivity and improving pulmonary vascular hemodynamics. Methods: A comprehensive search of PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Library was conducted through December 2024. Randomized clinical trials and prospective observational studies assessing PADN in PH were included. Primary endpoints were changes in outcomes from six-minute walk distance (6MWD), mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), cardiac output (CO), and right ventricular function parameters. Secondary outcomes included clinical worsening, rehospitalization, transplantation, and all-cause mortality. Random-effects models were used to calculate pooled mean differences (MDs) and odds ratios (ORs) with 95% confidence intervals (CIs). Subgroup analyses were performed according to pulmonary hypertension phenotype and study design, and sensitivity analyses were conducted to assess robustness of pooled estimates. Results: Nine studies involving 454 patients were included. PADN significantly improved functional capacity (6MWD: MD = 92.03 m; 95% CI 46.37–137.68; p < 0.001) and reduced mPAP (MD = −11.84 mmHg; p < 0.001) and PVR (MD = −4.88; p < 0.001). Cardiac output increased significantly (MD = 0.55 L/min; p < 0.001), with improvements observed in right ventricular functional indices. PADN was associated with a lower risk of clinical worsening (OR = 0.30; p = 0.001) and rehospitalization (OR = 0.07; p < 0.001), whereas no significant difference was observed in all-cause mortality (OR = 0.53; p = 0.12). Considerable heterogeneity was observed across functional and hemodynamic outcomes, reflecting variability in study design, patient populations, and PADN techniques. Conclusions: PADN significantly improves exercise capacity and pulmonary hemodynamics in patients with PH, particularly in those with persistent symptoms despite medical therapy. Although PADN reduces clinical deterioration and rehospitalization, its impact on long-term survival remains uncertain. Further large-scale, multicenter randomized trials are needed to better define optimal patient selection and determine long-term clinical benefit.