Pulnovo says two U.S. participants have undergone PULSE-LHD procedures at Henry Ford. The registry estimates total enrolment at 750, including operator roll-ins. After any required roll-ins, the trial randomises eligible participants 1:1 to PADN or a sham procedure; both groups receive guideline-directed medical therapy. No efficacy or safety results are posted.
Pulnovo reported late on 23 August 2026 ET that two participants underwent procedures at Henry Ford Hospital in Detroit. The company called them PULSE-LHD’s first U.S. patients.
The public record for NCT07214376 permits operator roll-in cases before a site starts randomising. Pulnovo did not say whether the two Henry Ford participants were roll-ins or members of the randomised cohort.
Pulnovo’s release contains no efficacy or safety data.
01What happened at Henry Ford
Henry Ford is one of six sites coded as recruiting in the registry snapshot dated 21 August 2026. The procedures were performed by Waleed Al-Darzi, Vikas Aggarwal and Brian O’Neill, according to Pulnovo. Al-Darzi is the Henry Ford site investigator; the registry names Gregg Stone of Mount Sinai as overall principal investigator.
The registry still labels 30 July 2026 as an estimated start date, while the release gives neither consent nor procedure dates.
02PULSE-LHD design, masking and follow-up
ClinicalTrials.gov classifies PULSE-LHD as an interventional device study, with phase listed as not applicable. After any operator roll-ins, eligible participants are randomised 1:1 to the Enhancor radiofrequency PADN procedure plus guideline-directed medical therapy, or to a sham procedure plus the same medical therapy.
Randomisation is stratified by site and core-lab left-ventricular ejection fraction: 40% or below versus above 40%. The participant and outcome assessor are masked. The operator is not.
The registry estimates primary completion on 31 December 2029 and study completion on 31 December 2031. Visits are listed at 1, 6, 12, 24 and 36 months. It shows an independent data monitoring committee and no plan to share individual participant data.
03PULSE-LHD shifts the primary endpoint from function to clinical events
The primary efficacy measure is time to first major heart-failure event. Six-minute walk distance, NT-proBNP and Kansas City Cardiomyopathy Questionnaire score sit among the secondary outcomes.
PADN-5, the main prior randomised study in this population, enrolled 98 participants and measured change in six-minute walk distance at six months. PULSE-LHD instead measures time to the first major heart-failure event.
The registered primary safety analysis compares treatment-arm device- or procedure-related major adverse events with a performance goal. It does not compare the randomised arms, and the numeric performance goal is not public.
04What PADN-5 showed and what remained uncertain
PADN-5 randomised 98 people with combined pre- and post-capillary pulmonary hypertension at four centres. Participants assigned to PADN improved their six-minute walk distance by 83 metres at six months, compared with 15 metres in the sildenafil-plus-sham group. Pulmonary vascular resistance was 4.2 versus 6.1 Wood units.
Clinical worsening at six months was a post hoc outcome: 16.7% with PADN and 40.0% with sildenafil plus sham. At three years, a follow-up report from the same 98-person cohort recorded clinical worsening in 37.5% of the PADN group and 62.0% of the control group. Cardiopulmonary mortality was 18.8% versus 32.0%; that difference was not statistically significant.
PADN-5’s main safety endpoint was pulmonary embolism. By the end of the six-month study, seven all-cause deaths and two pulmonary emboli had occurred; the published abstract does not assign causality.
PADN-5 was a 98-participant, single-blind study at four centres in China, and the active control received sildenafil. Current guidance does not recommend PAH-approved drugs broadly in PH-LHD because trials have shown no benefit and possible harm. PADN-5 therefore does not show how PADN compares with guideline-directed medical therapy alone.
The paper lists Nanjing First Hospital as funder and states that Pulnovo supplied the PADN catheters. Shao-Liang Chen disclosed that he invented PADN-related patents but did not own them.
PULSE-LHD gives both randomised groups the same guideline-directed medical therapy, scripts the sham procedure, and uses a clinical-event composite as the primary efficacy endpoint. Its estimated total enrolment is 750, including an undisclosed number of roll-ins.
05How the Enhancor procedure is meant to work
PADN applies radiofrequency energy near sympathetic nerves around the pulmonary artery. The proposed effect is reduced sympathetic signalling, pulmonary vasoconstriction and vascular remodelling, which could lower right-ventricular afterload.
The registered procedure begins with pulmonary angiography. The catheter is positioned at the left pulmonary-artery ostium and the distal main pulmonary-artery bifurcation. Radiofrequency applications target 50°C, within a 45–55°C range, for 120 seconds each. The record says approximately three ablations at both regions but does not make the exact total unambiguous.
The disease being targeted is combined pre- and post-capillary pulmonary hypertension associated with left-heart disease. These patients have elevated pressure transmitted from the left side of the heart plus pulmonary vascular disease. The public eligibility list says diagnosis must be confirmed by right-heart catheterisation, but it does not disclose the exact mean pulmonary-artery pressure, wedge-pressure or pulmonary vascular-resistance cut-offs used by the protocol.
06PH-LHD has no approved disease-specific therapy
A 2026 JACC state-of-the-art review describes PH-LHD as the most prevalent form of pulmonary hypertension, accounting for an estimated 65–80% of cases. No drug or intervention is approved specifically for PH-LHD; treatment still targets the underlying heart failure, valve disease and volume status.
The review says earlier PAH-drug trials produced no benefit and may be harmful in PH-LHD. It lists PADN, sotatercept, relaxin analogues, levosimendan, transcatheter atrial shunts and pericardiotomy as investigational. It identifies recruitment, phenotype heterogeneity, and non-standardised functional and haemodynamic outcomes as barriers to PH-LHD trials.
The 164-participant CADENCE phase 2 trial reported a 24-week treatment effect on pulmonary vascular resistance with sotatercept in severe CpcPH and heart failure with preserved ejection fraction. Pulmonary vascular resistance was the primary endpoint; the study was not powered for mortality or heart-failure hospitalisation. Sotatercept is not approved for PH-LHD.
Eligibility requires symptomatic chronic heart failure despite maximally tolerated guideline-directed therapy, NYHA class II–IVa, a six-minute walk distance of 100–450 metres, and NT-proBNP of at least 600 pg/mL when LVEF is 40% or below and at least 200 pg/mL when LVEF is above 40%. The trial excludes predominant WHO Group 1, 3, 4 or 5 pulmonary hypertension.
The 21 August registry version listed six recruiting U.S. sites for an estimated 750 participants. Feasibility will depend on adding sites and recruiting eligible, catheter-confirmed participants at each site.
07IDE and CMS coverage do not approve the device
The Enhancor system is investigational in the United States. An investigational device exemption permits a device to be studied so safety and effectiveness data can be collected. It is not FDA clearance, approval or endorsement.
CMS lists PULSE-LHD as IDE G250159, Category B, approved for coverage on 24 March 2026. Medicare may cover the Category B device and qualifying routine trial services, subject to applicable coverage requirements. It is not general commercial reimbursement.
Pulnovo announced a $100 million financing round led by Medtronic in April 2026. The round eases near-term financing risk but leaves PULSE-LHD’s evidentiary requirements unchanged.
Gradient Denervation Technologies’ PreVail-PH2 is a separate U.S. early-feasibility PADN study using ultrasound. Gradient reported its first U.S. participant enrolled in March 2024. PreVail-PH2 therefore predates PULSE-LHD in the United States. Pulnovo’s announcement covers its own first U.S. participants.
08Witfire Evidence Risk Score
Competition 4.5 × 25% = 1.125
Capital 2.0 × 20% = 0.40
Evidence 6.0 × 15% = 0.90
Execution 4.0 × 10% = 0.40
The score is an editorial programme-risk model, not an estimated failure probability. The $100 million financing round lowers the capital component; the device’s investigational U.S. status keeps regulatory exposure high.
09What to watch in PULSE-LHD
- Roll-in versus randomised status. The next public update should say when the first 1:1 assignment occurred and separate operator training from efficacy enrolment.1:1
- Recruiting-site expansion. The registry version dated 21 August listed six recruiting sites. Track additions to the network and recruitment per site against estimated total enrolment of 750.6 → ?
- Public protocol or analysis plan. Exact right-heart catheter thresholds, sample-size assumptions, the safety performance goal and the primary timing rule remain undisclosed.4 gaps
- Thirty-day device and procedure safety. Pulmonary-artery injury, bleeding, vascular complications and nerve injury are among the listed events. The first 30-day report will show whether any occurred.30 days
- China PADN-HF-PH results. Pulnovo says results from the separate NCT05824923 study are planned for ESC 2026. Until presented, they are not evidence in this analysis.ESC 2026
- PULSE-LHD primary completion. The current estimate is 31 December 2029, with full study completion two years later.2029 / 2031
10Verdict on the first two PULSE-LHD procedures
Henry Ford has now performed two PULSE-LHD procedures. Pulnovo’s report contains no outcome data.
Compared with PADN-5, PULSE-LHD holds medical therapy constant, uses a scripted sham procedure, masks participants and outcome assessors, and measures major heart-failure events.
The trial must recruit an estimated 750 total participants with catheter-confirmed CpcPH, preserve masking in a procedure study, meet its 30-day safety performance goal, and show an effect on clinical events.
PULSE-LHD has started; the registry estimates primary completion in December 2029.
11FAQ
What is the PULSE-LHD trial?
PULSE-LHD, NCT07214376, is an estimated 750-participant U.S. device study in combined pre- and post-capillary pulmonary hypertension associated with left-heart disease. It includes operator roll-ins, then randomises eligible participants 1:1 to PADN plus guideline-directed medical therapy or a sham procedure plus the same therapy.
Were the first two PULSE-LHD patients randomised?
Pulnovo did not say. The registry permits operator roll-in procedures before randomisation, so the first two Henry Ford participants should not be described as randomised unless the sponsor or registry confirms it.
Is pulmonary artery denervation FDA approved?
No. The Enhancor system is investigational in the United States. The IDE permits it to be studied; it does not clear or approve the device for sale or establish safety and effectiveness.
What does PULSE-LHD measure?
The primary efficacy endpoint is time to first major heart-failure event: cardiovascular death, heart transplant or durable LVAD, heart-failure hospitalisation, or outpatient worsening heart failure. The primary safety endpoint is a 30-day treatment-arm composite of device- or procedure-related major adverse events against a performance goal.
How does PULSE-LHD differ from PADN-5?
PADN-5 randomised 98 participants and used six-minute walk distance at six months as its primary endpoint, with sildenafil plus sham as control. PULSE-LHD is larger, gives both randomised groups the same guideline-directed medical therapy and uses a clinical heart-failure composite as primary efficacy endpoint.
Are PULSE-LHD results available?
No results were posted on ClinicalTrials.gov as of 24 August 2026. The registry estimates primary completion on 31 December 2029 and study completion on 31 December 2031.
What does CMS Category B coverage mean?
For a qualifying Category B IDE study, Medicare may cover the investigational device and routine, related trial services. It does not mean the device has FDA marketing approval or that Medicare covers routine commercial use.
Computed in this brief: PULSE-LHD’s 750 estimated total enrolment is 7.65 times the 98-person PADN-5 randomised sample, but the comparison is not like-for-like because the PULSE total includes an undisclosed number of roll-ins. PADN-5’s three-year clinical-worsening rates differ by 24.5 percentage points (62.0% minus 37.5%). The Witfire score is 4.925 before rounding.
Known public-record gaps: exact right-heart catheter haemodynamic thresholds, the numeric 30-day safety performance goal, sample-size assumptions, statistical analysis plan, randomisation-concealment method, roll-in/randomised split and an internally consistent primary-efficacy timing definition. No PULSE-LHD results were posted when checked on 24 August 2026.
Disclosure: Editorial analysis, not investment or medical advice. The Witfire Evidence Risk Score weights Regulatory Exposure 30%, Competitive Displacement 25%, Capital Position 20%, Evidence Integrity 15% and Execution & Credibility 10%.
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