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Key result
Pulmonary-artery denervation cuts 2-year clinical worsening ~51% versus medical therapy alone.
- HR 0.49
- 95% CI 0.30-0.82
- P=0.006
- n=264
Why the trial?
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?
Key Points
- To assess the clinical efficacy and safety of pulmonary-artery denervation added to guideline-directed medical therapy in patients with pulmonary hypertension associated with left heart disease and heart failure.
- Multicenter randomized trial in China enrolling 264 patients with pulmonary hypertension associated with left heart disease and heart failure (NCT05824923).
- Patients were randomly assigned 1:1 to receive pulmonary-artery denervation plus guideline-directed medical therapy (n=134) or guideline-directed medical therapy alone (n=130), followed for a median of 338 days.
- The Kaplan–Meier estimated 2-year incidence of clinical worsening was 25.7% in the denervation group versus 51.5% in the medical-therapy group (hazard ratio, 0.49; 95% CI, 0.30 to 0.82; P=0.006).
- Access-site hematomas occurred in 2 patients in the denervation group and 1 patient in the medical-therapy group, with no other procedural complications and similar overall adverse event rates between groups.
Evidence details
What drove the result?
| Outcome | PADN + GDMT | GDMT alone |
|---|---|---|
| Clinical worsening: death, transplant, HF hospitalisation, outpatient HF worsening, or 6MWD decline | 25.7% | 51.5% |
| 2-year Kaplan-Meier estimates · HR 0.49 (95% CI 0.30-0.82; P=0.006); components not reported | ||
Limitations & tradeoffs
Patient burden
access-site hematoma in 2 vs 1 patients; no other procedural complications reported.
Design limitations
no sham control, the composite includes outpatient worsening and 6-minute-walk decline, which are open to bias in an unblinded comparison, and the trial was funded by the device manufacturer (Pulnovo Medical) and others.
Statistical certainty
median follow-up was only 338 days while the primary result is a 2-year Kaplan-Meier estimate.
Representation
conducted entirely in China, which may limit generalizability.
Structured PICO
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?
P
Population
264 patients with pulmonary hypertension associated with left heart disease and heart failure, followed for a median of 338 days.
I
Intervention
Pulmonary-artery denervation added to guideline-directed medical therapy
C
Comparator
Guideline-directed medical therapy alone
O
Outcome
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-upcomposite
Main Result
Hazard Ratio: 0.49 (95% CI 0.3–0.82)
Absolute Event Rate: 25.7% vs 51.5%
p-value: p=0.006
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.
Discussion
Key questions
No takes yet. Share an insight, caveat, or question.
Where experts stand
Experts see pulmonary-artery denervation as a provocative new device-based approach for heart-failure-related pulmonary hypertension, but caution that the lack of a sham control and the absence of significant individual endpoints temper enthusiasm.
Clinicians broadly acknowledge this as a positive signal for a condition with few treatment options, but several flag that no individual component of the primary endpoint reached significance on its own and the trial lacked a sham-control arm. The live question is whether these results can hold up in a larger, sham-controlled trial with hard clinical endpoints before the approach enters practice.
Agreement
Multiple clinicians recognize pulmonary-artery denervation as a promising new intervention for Group 2 pulmonary hypertension, an area of significant unmet need, while noting the trial met its composite primary endpoint.
3 clinicians say this directly
3 takes classified by contention axis so far — the map appears as more land.
Still unclear
Whether individual clinical endpoints such as all-cause mortality can be significantly reduced remains unresolved. Experts note the absence of a sham-control arm, leaving open whether an invasive placebo effect contributed to the composite result. A larger sham-controlled trial with hard endpoints is widely seen as the necessary next step.
Key expert perspectives
MAMohammed 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.”
Denervation showed benefit on the composite but no significant reduction in all-cause mortality
Topol highlights that while the trial showed benefit for pulmonary-artery denervation compared with guideline-directed medical therapy, there was no significant reduction in all-cause mortality. He frames pulmonary hypertension from heart failure as carrying a poor prognosis, making the incomplete endpoint story notable.
Distilled from their postX post
Pulmonary artery denervation in left heart failure related pulmonary hypertension is striking
Watson reacted with surprise to the results, expressing that the finding of pulmonary artery denervation working in left heart failure related pulmonary hypertension was noteworthy.
Distilled from their postX post
Implication
Pulmonary-artery denervation halves clinical worsening in PH-LHD; extends interventional options beyond medical therapy in this population.
Abstract
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.
Coverage & sources
Journal, society, and media accounts. Useful signal, not independent expert judgment.
Cite This Study
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).