Pulnovo Medical has reported randomized clinical evidence showing that catheter-based pulmonary artery denervation significantly reduced clinical worsening in patients with pulmonary hypertension caused by left heart disease and heart failure. In the 264-patient PADN-HF-PH trial, the estimated two-year incidence of clinical worsening was 25.7% among patients receiving pulmonary artery denervation plus guideline-directed medical therapy compared with 51.5% among those receiving medical therapy alone. The hazard ratio was 0.49, corresponding to a 51% reduction in relative risk, with a 95% confidence interval of 0.30 to 0.82 and a p-value of 0.006. The findings were presented at ESC Congress 2026 and simultaneously published in The New England Journal of Medicine.
The result represents a substantially stronger evidentiary milestone than Pulnovo’s recent announcement that the first U.S. patients had undergone procedures in the separate PULSE-LHD investigational study, which PDN has already covered. The new story is the outcome of a completed randomized trial involving 134 patients assigned to PADN plus medical therapy and 130 assigned to medical therapy alone, with a median follow-up of 338 days. It provides the clinical rationale for the much larger U.S. development program, but it does not mean the Enhancor/PADN system is FDA approved. The registered U.S. PULSE-LHD study describes the device as unapproved or uncleared and plans a 750-patient placebo-procedure-controlled evaluation.
What counted as clinical worsening in the PADN-HF-PH trial?
The trial used a composite endpoint intended to capture several ways in which pulmonary hypertension and heart failure can deteriorate. A qualifying event included death, heart or lung transplantation, hospitalization for heart failure, outpatient worsening requiring intravenous diuretic therapy, or a clinically significant decline in six-minute walking distance. Using a composite allowed investigators to assess more than survival alone because patients with chronic heart failure can experience repeated hospitalizations and progressive loss of exercise capacity long before death.
The two-year Kaplan-Meier estimate of 25.7% clinical worsening with PADN versus 51.5% with medical therapy therefore represents a difference across this broader spectrum of deterioration. The absolute difference was 25.8 percentage points, while the relative hazard was roughly halved. Because median follow-up was 338 days, the two-year percentage is a time-to-event estimate rather than a statement that every participant had already been observed for two complete years, an important distinction when interpreting Kaplan-Meier results.
Did pulmonary artery denervation also reduce repeated heart-failure events?
Yes. Pulnovo reported that the annualized rate of first and recurrent clinical-worsening events was 36.3 per 100 patient-years in the PADN group compared with 56.3 per 100 patient-years with medical therapy alone. The corresponding hazard ratio was 0.59, with a 95% confidence interval of 0.39 to 0.89, representing a 35.5% reduction in the recurrent-event rate.
Recurrent-event analysis is relevant in heart failure because one patient may be hospitalized several times, and counting only the first event can conceal a substantial proportion of the disease burden. A therapy that merely delays the first hospitalization by a short period would be less clinically valuable than one that reduces repeated deteriorations over time. The recurrent-event signal therefore gives the PADN result more depth, although the larger U.S. trial will be important for confirming how reproducible this effect is in a geographically different and rigorously controlled population.
How does pulmonary artery denervation actually work?
Pulmonary artery denervation is designed to modify sympathetic nerve activity around the pulmonary arteries. Excessive sympathetic signaling has been implicated in pulmonary vascular constriction, remodeling and adverse interactions between the pulmonary circulation and right side of the heart. Pulnovo’s catheter delivers radiofrequency energy at selected locations within the pulmonary arterial circulation with the aim of disrupting this overactive nerve signaling.
The concept has some similarity to renal denervation in systemic hypertension, where energy is delivered to nerves surrounding renal arteries, but the disease target and anatomy are different. In PH-LHD, the underlying problem originates from left-sided heart disease, which raises pressures backward through the pulmonary circulation and can eventually produce pulmonary vascular remodeling and increased resistance. PADN does not repair the failing left ventricle or valve disease responsible for the original pressure burden; rather, it attempts to modify an additional neurovascular mechanism contributing to pulmonary hypertension.
Why is PH-LHD such a difficult treatment problem?
Pulmonary hypertension associated with left heart disease is often referred to as WHO Group 2 pulmonary hypertension. It can occur in patients with heart failure with reduced or preserved ejection fraction and in people with valvular or other structural heart disease. Treatment has traditionally focused on optimizing the underlying left-heart condition because drugs developed for pulmonary arterial hypertension have generally not translated straightforwardly into effective therapies for Group 2 disease.
That creates a significant therapeutic gap for patients whose left-heart treatment is optimized yet pulmonary pressures, vascular resistance and symptoms remain substantial. These patients can develop worsening shortness of breath, declining exercise tolerance, right-ventricular dysfunction and repeated heart-failure hospitalizations. PADN is therefore attempting to intervene directly in the pulmonary vascular component of a disease for which there is currently no broadly approved intervention targeting this mechanism.
What happened to walking capacity, quality of life and biomarkers?
Pulnovo reported a net 24.8-meter improvement in six-minute walk distance at 12 months relative to control. The risk of experiencing a decline of at least 10% in six-minute walk distance was reduced by 63%, corresponding to a hazard ratio of 0.37. Patients receiving PADN also showed better Kansas City Cardiomyopathy Questionnaire overall summary scores and a greater reduction in NT-proBNP at six months, providing directional consistency across functional status, patient-reported health and a biomarker associated with cardiac stress.
These secondary findings are useful because an intervention producing fewer clinical events but no improvement in symptoms or functional capacity might be more difficult to understand biologically. Here, several measurements moved in the same favorable direction. Nevertheless, individual secondary endpoints have different statistical hierarchies and should not all be treated as equivalent to the prespecified primary outcome.
What did the randomized trial show about procedural safety?
Access-site hematomas occurred in two patients receiving PADN and one patient assigned to medical therapy, and investigators reported no other procedural complications. Adverse events during follow-up occurred with similar frequency between groups. The NEJM abstract therefore presents a relatively reassuring initial safety profile for the procedure in this 264-patient population.
That does not eliminate procedural risk. Pulmonary artery intervention requires catheter access and manipulation within the cardiopulmonary circulation, and larger populations are needed to quantify uncommon complications reliably. Commercial adoption would also require consistent procedural performance across operators and centers rather than only experienced investigators participating in development trials.
Why is the 750-patient U.S. PULSE-LHD trial still necessary after a positive NEJM study?
Regulatory evidence needs to establish that benefit is reproducible under conditions relevant to the market in which authorization is being sought. ClinicalTrials.gov describes PULSE-LHD as a randomized placebo-procedure-controlled study evaluating the Enhancor PADN system in patients with combined pre- and post-capillary pulmonary hypertension associated with left heart disease. Estimated enrollment is 750 participants, and the study uses a sham procedure control, a particularly important feature for an intervention whose subjective endpoints can be influenced by knowing that a procedure was performed.
The U.S. registry explicitly identifies the system as an FDA-regulated device that is unapproved or uncleared. CMS has granted the study Category B investigational-device status, which relates to Medicare coverage of certain study-related device costs and is not an FDA marketing authorization.
The larger trial therefore has several jobs. It needs to confirm safety across many more procedures, demonstrate benefit under a placebo-procedure-controlled design, show that outcomes are reproducible outside the original Chinese trial, and generate the regulatory evidence necessary for a potential U.S. submission.
How should the 51% risk reduction be interpreted?
A relative reduction of 51% is large for a cardiovascular intervention, which is precisely why replication matters. The estimated absolute separation in two-year clinical worsening was also substantial, but the study included only 264 patients and was conducted in China. Treatment practice, patient selection, procedural experience and background heart-failure care can differ between regions, so the result should be viewed as strong randomized evidence rather than the final word on efficacy.
The study was funded by Pulnovo Medical and other organizations, and Pulnovo supplied the denervation catheters, disclosures that are clearly reported with the NEJM publication. Industry funding does not invalidate a randomized trial, but independent replication and regulatory review remain important when results are unusually favorable.
What does the new evidence mean for Pulnovo’s U.S. program?
The NEJM publication materially strengthens the scientific rationale underlying PULSE-LHD. When Pulnovo announced its first U.S. procedures, no efficacy results from the American study existed, and those procedures alone could not indicate whether the system worked. The 264-patient randomized dataset now gives physicians and regulators a clearer reason to believe that the mechanism deserves definitive testing.
The next decisive milestone will nevertheless come from the larger sham-controlled program. If PULSE-LHD reproduces a substantial reduction in heart-failure deterioration while maintaining acceptable safety, pulmonary artery denervation could become an entirely new interventional category within Group 2 pulmonary hypertension. If the effect shrinks markedly under sham control or a more diverse population, the field will have to understand why. The current study has answered whether PADN can produce a compelling randomized signal; the U.S. program must now determine whether that signal is robust enough for routine clinical practice.
