Prolonged pulmonary venous congestion culminates in pulmonary hypertension, defined as a mean pulmonary arterial pressure > 20 mmHg and pulmonary artery wedge pressure >15 mmHg at rest, as determined by right heart catheterization. Pulmonary hypertension secondary to heart failure (PH-HF) is further stratified into isolated post-capillary pulmonary hypertension (Ipc-PH, pulmonary vascular resistance (PVR) is ≤2 Woods Unit) and combined pre- and post-capillary pulmonary hypertension (Cpc-PH, PVR > 2 Woods Unit), the later reflecting additional pulmonary vascular constriction or remodeling in addition to passive PH. While medications tailored for World Health Organization defined Group I pulmonary arterial hypertension are not endorsed for PH-HF according to current guidelines, the coexistence of pulmonary hypertension exacerbates the severity of heart failure. Given the presence of pulmonary arterial vasoconstrictor and heightened sympathetic nervous activity in patients with heart failure, the PADN-5 study has demonstrated the safety and efficacy of pulmonary artery denervation (PADN) for patients with CpcPH, characterized by the improvements in left ventricular ejection fraction, cardiac output, clinical outcome, and reductions in left atrial pressure, pulmonary arterial pressure, and PVR. Our objective is to assess the feasibility, safety, and efficacy of PADN for patients with heart failure independent of left ventricular ejection fraction (HFrEF or HFpEF) without pulmonary hypertension (N=30, 15 with HFrEF and another 15 with HFpEF).

We conducted a safety and proof-of-principle cohort study at a single centre in China. Eligible patients, aged 18 years or greater, had a documented history of chronic (≥6 months) ischaemic or non-ischaemic cardiomyopathy. They also met the American College of Cardiology/American Heart Association (ACC/AHA) stage C heart failure criteria, with New York Heart Association (NYHA) class III or ambulatory class IV symptoms. Additionally, participants were required to have been receiving guideline-directed medical therapy for at least three months, as tolerated per ACC/AHA guidelines.

Further inclusion criteria encompassed a pulmonary artery wedge pressure exceeding 15 mm Hg, a mean pulmonary arterial pressure less than or equal to 20 mm Hg, and pulmonary vascular resistance (PVR) less than or equal to 2 Woods Unit. Patients were ineligible if they lacked patent femoral venous or inferior vena cava/right jugular vein access, or exhibited a plasma N-terminal prohormone B-type natriuretic peptide (NT-proBNP) level below 300 pg/ml, had experienced a stroke or thromboembolic event within the preceding 12 months, had patent foramen ovale or atrial septal defect, or presented with severe (grade 4) mitral regurgitation. Patients with coagulation disorders or contraindications for oral anticoagulation, as well as those harboring pulmonary artery, right atrial, or right ventricular thrombus, were also excluded.

Inclusion Criteria:

• aged 18 years or greater, had a documented history of chronic (≥6 months) ischaemic or non-ischaemic cardiomyopathy; ACC/AHA stage C heart failure criteria, NYHA class III or ambulatory class IV symptoms; on GDMT for heart failure at least three months; PAWP exceeding 15 mm Hg, mean PAP less than or equal to 20 mm Hg, and PVR less than or equal to 2 Woods Unit

Exclusion Criteria:

Patients lacked patent femoral venous or inferior vena cava/right jugular vein access; had experienced a stroke or thromboembolic event within the preceding 12 months, had patent foramen ovale or atrial septal defect, or presented with severe (grade 4) mitral regurgitation; had coagulation disorders or contraindications for oral anticoagulation; had harboring pulmonary artery, right atrial or right ventricular thrombus; had undergone pacemaker implantation within 1 month.

Patients with heart failure