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Pulmonary Denervation for Heart Failure–Related Pulmonary Hypertension
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?
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
Authors
Discussion
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 flag the lack of a sham control and the absence of significant individual endpoint components as reasons for caution before practice adoption.
Clinicians broadly acknowledge that pulmonary artery denervation reduced clinical worsening in a population with few treatment options, and several call the result exciting. However, enthusiasm is tempered by the open-label design without a sham control and by the observation that no individual component of the composite endpoint reached significance on its own. The central question is whether a sham-controlled trial with hard endpoints will confirm the benefit or reveal a large placebo effect.
Agreement
Multiple clinicians agree that pulmonary artery denervation reduced clinical worsening compared with guideline-directed medical therapy in this population, representing a notable signal for a condition with significant unmet need.
4 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 with hard endpoints, as several voices note the invasive placebo effect can be powerful. It also remains unclear whether the result applies equally to HFrEF and HFpEF subgroups, and why no individual component of the composite reached significance on its own.
Key expert perspectives
Denervation showed benefit but no significant reduction of all-cause mortality
Topol highlights that while the randomized trial showed benefit for the composite, there was no significant reduction of all-cause mortality. He frames the combination of pulmonary hypertension and heart failure as carrying a poor prognosis, underscoring the clinical stakes.
Distilled from their postX post
MGMartha GulatiCardiologistPractice takeAug 31
A provocative new device-based approach for Group 2 PH
Gulati calls pulmonary artery denervation a provocative new device-based approach for Group 2 PH, noting clinical worsening dropped from roughly 52% to 26% at 2 years with denervation added to GDMT.
Distilled from their postX post
Gregg W. StoneInterventional / Structural Cardiology · Icahn School of Medicine at Mount Sinai / Mount Sinai Health SystemLive reportingAug 30Trial co-author reports a positive result across 25 centers in 264 patients
Stone, a trial investigator, reports the PADN-HF-PH trial randomized 264 patients with left-heart failure and pulmonary hypertension (mPAP >20 mmHg and PCWP >15 mmHg) at 25 centers to PADN plus GDMT versus GDMT alone, with simultaneous NEJM publication.
Distilled from their postX post
Implication
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
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.
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).