What happened
Pulmonary-artery denervation cuts 2-year clinical worsening ~51% versus medical therapy alone.
“Despite major advances in pharmacologic and device-based therapies, pulmonary hypertension remains one of the strongest predictors of hospitalization, right ventricular failure, and death in patients with left heart disease and heart failure. … Additional long-term follow-up will be important to determine whether the observed mid-term improvements translate into sustained reductions in mortality and hospitalization for HF.”
Dr. Hang Zhang
“Most pulmonary hypertension is from heart failure and that combination carries a poor prognosis. A randomized trial tested denervation of the pulmonary artery (PADN) compared with guideline directed medical therapy (GDMT) showing benefit (but no significant reduction of all-cause”
Topol notes that most pulmonary hypertension stems from heart failure and that the combination carries a poor prognosis. He says the randomized trial of PADN versus GDMT showed benefit but no significant all-cause reduction.
Adding denervation to guideline-directed therapy markedly reduced clinical worsening at 2 years.
Suliman flags PADN-HF-PH as an important ESC 2026 result. He reports that pulmonary-artery denervation added to guideline-directed therapy markedly reduced clinical worsening in pulmonary hypertension due to left-heart disease and HF, with estimated clinical worsening of about 26% at 2 years.
“PADN-HF-PH #ESCCongress #PH #PulmonaryHypertension 264 patients with PH due to left heart disease/HF → pulmonary artery denervation + GDMT GDMT alone At 2 yrs: Clinical worsening ~ with denervation: 26% vs ~52% Provocative new device-based approach for Group 2 PH,”
X ↗Mohammed Al-Qadami
“PADN-PH-LHD: Pulmonary artery denervation reduced clinical worsening in Group 2 pulmonary hypertension: 25.7% vs 51.5%, HR 0.49. International sham-controlled trials with hard endpoints are still needed.”
X ↗Open questions from this trial that would benefit from expert input.
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Why the trial, tables, limitations, PICO, abstract, media & sources
Pulmonary hypertension due to left heart disease is common, worsens prognosis, and has no approved targeted therapy — pulmonary vasodilators have failed or caused harm. PADN-PH-LHD asked whether pulmonary artery denervation can safely improve outcomes in this group.
Does pulmonary-artery denervation added to guideline-directed medical therapy reduce clinical worsening in patients with pulmonary hypertension associated with left heart disease and heart failure?
| Outcome | PADN + GDMT | GDMT alone |
|---|---|---|
| Clinical worsening: death, transplant, HF hospitalisation, outpatient HF worsening, or 6MWD decline 2-year Kaplan-Meier estimates · HR 0.49 (95% CI 0.30-0.82; P=0.006); components not reported | PADN + GDMT 25.7% | GDMT alone 51.5% |
Does pulmonary-artery denervation added to guideline-directed medical therapy reduce clinical worsening in patients with pulmonary hypertension associated with left heart disease and heart failure?
Pulmonary-artery denervation significantly reduced the risk of clinical worsening compared to medical therapy alone in patients with pulmonary hypertension associated with left heart disease and heart failure.
Experts read pulmonary-artery denervation as a promising but unproven add-on for pulmonary hypertension caused by left heart disease, and say confirmation is needed before it changes practice.
Clinicians agree the procedure cut clinical worsening by a wide margin when added to standard heart failure therapy. The caution centers on what the benefit is made of: hard outcomes did not clearly improve, and the trial had no sham procedure. The open question is whether the effect holds up in larger, international, sham-controlled trials.
3 takes classified by contention axis so far — the map appears as more land.
Experts note there was no significant all-cause reduction. They also say international sham-controlled trials with hard endpoints are still needed to rule out a placebo effect from the invasive procedure.
Pulmonary-artery denervation halves clinical worsening in PH-LHD; extends interventional options beyond medical therapy in this population.
BackgroundPulmonary hypertension that is caused by left heart disease and is associated with heart failure may be driven by sympathetic overactivation leading to increased pulmonary vascular resistance, right ventricular dysfunction, and poor outcomes. Pulmonary-artery denervation may reduce sympathetic activity, although its clinical effects on left heart disease–associated pulmonary hypertension are unknown. MethodsWe conducted a multicenter, randomized trial in China involving patients with pulmonary hypertension associated with left heart disease and heart failure. Patients were randomly assigned in a 1:1 ratio to receive pulmonary-artery denervation plus guideline-directed medical therapy or to receive medical therapy alone. The primary outcome was clinical worsening — a composite of death, heart or lung transplantation, hospitalization for heart failure, outpatient worsening of heart failure, or a decline in the 6-minute walk distance — through the latest follow-up. ResultsA total of 264 patients underwent randomization: 134 to receive pulmonary-artery denervation plus medical therapy and 130 to receive medical therapy alone. During a median follow-up of 338 days, the Kaplan–Meier estimated 2-year incidence of clinical worsening was 25.7% in the pulmonary-artery denervation group and 51.5% in the medical-therapy group (hazard ratio, 0.49; 95% confidence interval, 0.30 to 0.82; P=0.006). Access-site hematomas occurred in two patients in the pulmonary-artery denervation group and in one patient in the medical-therapy group; there were no other procedural complications. Adverse events during follow-up occurred with similar frequency in the two groups. ConclusionsAmong patients with pulmonary hypertension associated with left heart disease and heart failure receiving guideline-directed medical therapy, pulmonary-artery denervation resulted in fewer events of clinical worsening than medical therapy. (Funded by Pulnovo Medical and others; PADN-HF-PH ClinicalTrials.gov number, NCT05824923.)
NEJM · ESC 2026 · RCT. PH from left heart disease: denervation halves 2-year clinical worsening PADN-PH-LHD: Pulmonary Denervation for Heart Failure–Related Pulmonary Hypertension 264 patients: PH from left heart disease and heart failure. Added to guideline-directed therapy: Denervation + GDMT vs GDMT alone. 2-year clinical worsening: death, transplant, HF events: PADN + GDMT 25.7% vs GDMT alone 51.5%. 0.49 hazard ratio. HR 0.49 (95% CI 0.30–0.82), P=0.006. Clinical worsening roughly halved. Safety: hematomas in 2 vs 1 patients: Access-site hematomas, No other complications, Similar adverse events. Bottom line: Denervation halves clinical worsening in PH-LHD, beyond medical therapy alone.
Journal, society, and media accounts. Useful signal, not independent expert judgment.
Zhang et al. (2026) conducted an RCT in Pulmonary hypertension associated with left heart disease and heart failure (n=264). Pulmonary-artery denervation vs. Guideline-directed medical therapy alone was evaluated on Clinical worsening (composite of death, heart or lung transplantation, hospitalization for heart failure, outpatient worsening of heart failure, or a decline in the 6-minute walk distance) (HR 0.49, 95% CI 0.30-0.82, p=0.006). Pulmonary-artery denervation reduced clinical worsening compared to medical therapy alone (25.7% vs 51.5%; HR 0.49; 95% CI 0.30-0.82; P=0.006).
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