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PADN-PH-LHDPulmonary HypertensionNew England Journal of Medicine
Pulmonary-Artery Denervation for Left Heart Disease-Associated Pulmonary Hypertension
Pulmonary Denervation for Heart Failure–Related Pulmonary Hypertension
View Full PaperWhy 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?
Population
264 patients with PH due to left heart disease + heart failure (134 vs 130), China
Comparison
Pulmonary-artery denervation + GDMT vs GDMT alone
Design
Multicenter randomized trial (1:1); no sham procedure in the control arm
Follow-up
Median 338 days
Key result
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).
Authors
Discussion
Member takes
Where experts stand
Experts see pulmonary-artery denervation as a promising new device approach for Group 2 pulmonary hypertension, but flag the lack of a sham control and the absence of significant individual endpoint components as important caveats before practice change.
Cardiologists are broadly impressed by the size of the treatment effect on clinical worsening, calling it a provocative new option for a condition with few therapies. However, enthusiasm is tempered by the open-label design without a sham procedure, the fact that no individual component of the composite reached significance, and the lack of a mortality benefit. The live question is whether sham-controlled trials with hard endpoints can confirm these findings and move the approach toward guideline adoption.
Agreement
Multiple experts note that while pulmonary-artery denervation reduced the composite of clinical worsening, no significant reduction in all-cause mortality was observed and no individual clinical component reached significance on its own.
2 clinicians say this directly
3 takes classified by contention axis so far — the map appears as more land.
Still unclear
Whether the benefit holds up in a sham-controlled trial, as the invasive placebo effect in device studies can be substantial. It also remains unclear why no individual component of the composite endpoint reached significance and whether all-cause mortality can be improved with longer follow-up or larger trials.
Key expert perspectives
Reacts with surprise to denervation results in left heart failure-related PH
Watson expresses strong surprise at the pulmonary artery denervation findings in left heart failure-related pulmonary hypertension.
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MGMartha GulatiCardiologistPractice takeAug 31
Provocative device approach for Group 2 PH, with clinical worsening roughly halved at 2 years
Gulati summarizes the trial as showing clinical worsening of about 26% versus 52% at two years with denervation plus GDMT compared to GDMT alone. She calls it a provocative new device-based approach for Group 2 PH.
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Denervation showed benefit but no significant reduction in all-cause mortality
Topol highlights that most pulmonary hypertension stems from heart failure and carries a poor prognosis. He notes the randomized trial showed benefit for denervation over guideline-directed medical therapy but flags that there was no significant reduction in all-cause mortality.
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Overview
Pulmonary-artery denervation halves clinical worsening in PH-LHD; extends interventional options beyond medical therapy in this population.
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
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.
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
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).