Pulnovo trial halves heart failure worsening risk

Pulnovo Medical announced that a new clinical trial cut the risk of clinical worsening in heart failure patients by 51%, according to data presented at the European Society of Cardiology Congress 2026 and published in The New England Journal of Medicine.

Reducing Risks in Heart Failure

The PADN-HF-PH trial involved 264 patients with pulmonary hypertension associated with left heart disease. Researchers evaluated the safety and efficacy of adding a therapy called Pulmonary Artery Denervation to standard Guideline-Directed Medical Therapy. The primary endpoint focused on clinical worsening, which includes death, heart or lung transplantation, hospitalization for heart failure, outpatient worsening requiring intravenous diuresis, or a significant decline in the 6-minute walk distance.

Over a median follow-up of 338 days, the group receiving PADN plus GDMT showed a 2-year incidence of clinical worsening at 25.7%. This figure stood in stark contrast to the 51.5% rate observed in the group treated with GDMT alone. The hazard ratio was 0.49, with a 95% confidence interval of 0.30 to 0.82, indicating a statistically significant reduction in the primary outcome.

The treatment also lowered the annualized rate of recurrent events. Patients in the PADN group experienced 36.3 events per 100 patient-years, compared to 56.3 events per 100 patient-years in the control group. This represents a 35.5% decrease in recurrent events overall.

The study was conducted as a multicenter, randomized, controlled investigation, bringing together investigators from leading cardiovascular centers. Leadership included Academician Yaling Han and co‑corresponding authors Professor Shao‑Liang Chen and Professor Gregg W. Stone, whose involvement showed the trial’s scientific rigor. By randomizing participants to either the combined approach or standard therapy alone, the design ensured that observed differences could be attributed to the intervention rather than external variables.

Because pulmonary hypertension and left‑sided heart disease intensify each other, patients often experience a heavier symptom burden and poorer outcomes. Existing therapeutic options primarily target the left‑heart component, leaving a therapeutic gap for the pulmonary vascular component. The addition of PADN directly addresses that gap by targeting overactive sympathetic signaling that drives vascular remodeling, thereby offering a mechanistic complement to conventional heart‑failure drugs.

Functional and Quality of Life Improvements

Beyond the primary safety and efficacy endpoints, the data showed improvements in functional capacity and biomarkers. At 12 months, patients in the PADN group walked an average of 24.8 meters further than those on standard therapy alone. The risk of a 10% or greater decline in the 6-minute walk distance was reduced by 63%.

Patients also reported better quality of life. The Kansas City Cardiomyopathy Questionnaire overall summary score improved in the PADN group, and levels of natriuretic peptide (NT‑proBNP) decreased more significantly compared to the control group.

Safety data from the trial were favorable. Access‑site hematomas occurred in only two patients receiving PADN and one patient on GDMT. No other procedural complications were reported. The therapy, which modulates overactivated sympathetic nerve activity, has already been included in several international clinical guidelines as an investigational intervention.

Quality‑of‑life gains were reflected not only in questionnaire scores but also in patients’ reported ability to perform everyday activities with less fatigue. The improvement in walking distance translated into greater independence for many participants, who could engage in routine tasks that had previously been limited by breathlessness or leg discomfort.

Biomarker trends further supported the clinical observations. The more pronounced fall in NT‑proBNP after the procedure indicated a reduction in cardiac wall stress, aligning with the observed functional benefits and suggesting a favorable impact on ventricular remodeling.

From a regulatory perspective, Pulmonary Artery Denervation has secured approvals across a dozen countries and regions, and clinicians have already performed roughly one and a half thousand procedures in patients with pulmonary arterial hypertension belonging to WHO Group 1. The current trial extends that experience into WHO Group 2, the classification that captures pulmonary hypertension secondary to left‑heart disease, thereby addressing a substantial unmet need.

Guideline bodies have taken note of the emerging evidence. The therapy is listed as an investigational interventional option in the 2022 ESC/ERS recommendations for pulmonary hypertension and has been cited in a total of seven major clinical guidelines to date. Such recognition signals a growing consensus that PADN may become an integral component of full heart‑failure management once further data confirm its long‑term benefits.

Ongoing investigations are broadening the scope of PADN to other subtypes of pulmonary hypertension, with additional trials slated to explore its role in diverse patient populations. By delivering a therapy that directly attenuates sympathetic overdrive, Pulnovo aims to shift the treatment paradigm from solely managing symptoms to modifying the underlying pathophysiology that drives disease progression.