Pulmonary Artery Denervation for the Treatment of Patients With Pulmonary Hypertension Secondary to Left-Sided Heart Failure: Rationale and Design of the Randomized Controlled PADN-HF-PH Trial

Abstract It remains uncertain whether combined pulmonary artery denervation (PADN) and guideline-directed medical therapy (GDMT) can effectively reduce clinical worsening in patients with heart failure (HF) and pulmonary hypertension (PH) associated with left heart disease. The PADN-HF-PH is a prospective, multicenter, randomized, controlled trial designed to assess the superiority of PADN for the treatment of patients with PH secondary to left-sided HF despite GDMT. A total of 264 subjects with PH secondary to left-sided HF who meet the inclusion criteria and none of the exclusion criteria will be dynamically randomized (at a 1:1 ratio) to the PADN plus GDMT group or the GDMT alone group, stratified by PH secondary to left-sided HF phenotypes and participating sites. The GDMT strategy is based on the 2023 European Society of Cardiology Guidelines for HF. The primary endpoint is the composite of all-cause death, rehospitalization due to HF, requirement for intravenous medication (inotropes, diuretics, or vasodilators) due to worsening of HF, referral for heart/lung transplantation, or 6-minute walk distance decreased by >10% or >30 m compared with baseline when the last enrolled subject has at least 6 months of follow-up. The safety endpoint is the incidence of adverse events of special interest, defined as complications occurring within 30 d after the PADN procedure. The PADN-HF-PH trial is specifically designed to evaluate the effectiveness and safety of adding PADN to GDMT in patients with PH associated with left heart disease who are experiencing HF. The primary objective of this study is to generate new evidence regarding the potential benefits of combining PADN with GDMT in reducing clinical worsening events among these patients (NCT05824923).