Pulnovo Medical has enrolled and treated the first two US patients in PULSE-LHD, a large randomized Investigational Device Exemption study testing whether radiofrequency pulmonary artery denervation can improve outcomes in patients with combined pre- and post-capillary pulmonary hypertension caused by left heart disease. The first procedures were performed at Henry Ford Hospital in Detroit, moving Pulnovo’s Enhancor system into a US development programme expected to enroll approximately 750 participants and follow patients for as long as three years. The trial is placebo-procedure controlled rather than open label and uses major heart-failure events as its primary efficacy endpoint, making it a substantially more demanding test than asking whether pulmonary pressures or walking distance improve shortly after the procedure.
PULSE-LHD is particularly important because WHO Group 2 pulmonary hypertension associated with left heart disease represents a much broader population than the Group 1 pulmonary arterial hypertension cohorts in which pulmonary artery denervation has generated much of its previous evidence. Pulnovo cites estimates that PH-LHD accounts for roughly 65% to 80% of pulmonary hypertension cases, yet the company notes that there is no therapy specifically approved to treat PH-LHD itself. The Enhancor system remains investigational in the United States and has not been cleared or approved for this indication.
What exactly is pulmonary artery denervation trying to change?
Pulnovo’s procedure is designed around the hypothesis that excessive sympathetic nerve activity surrounding the pulmonary arteries contributes to pulmonary vascular remodeling and disease progression. The Enhancor catheter is inserted through the vasculature and delivers radiofrequency energy at defined points around the pulmonary artery, attempting to disrupt selected sympathetic nerve pathways without surgically opening the chest.
In PULSE-LHD, the protocol calls for pulmonary artery angiography to define anatomy before the ablation catheter is positioned around the left pulmonary artery ostium and distal main pulmonary artery bifurcation. Approximately three ablations are planned at each location at a target temperature around 50 degrees Celsius for 120 seconds, while all participants continue guideline-directed medical therapy for their underlying heart failure. The control group undergoes a simulated procedure plus the same medical-management framework, an important design choice because invasive interventions can generate substantial placebo effects on symptoms and functional measures.
The biological objective differs from opening a blocked vessel or mechanically supporting the heart. PADN is attempting to modify neural regulation of the pulmonary circulation, potentially reducing vasoconstriction and remodeling over time. That makes the intervention closer conceptually to renal denervation for systemic hypertension than to conventional pulmonary vasodilator therapy.
Why is Group 2 pulmonary hypertension such a difficult therapeutic target?
PH-LHD develops because elevated pressures originating on the left side of the heart are transmitted backward into the pulmonary circulation. In some patients, chronic pressure exposure is followed by additional remodeling of pulmonary vessels, producing combined post-capillary and pre-capillary disease. These patients can remain symptomatic despite optimized heart-failure therapy and may have particularly poor exercise capacity and prognosis.
The challenge is that pulmonary vasodilators developed for Group 1 pulmonary arterial hypertension cannot simply be assumed to work in Group 2 disease. Altering pulmonary vascular tone in someone with elevated left-sided filling pressures can produce different hemodynamic consequences, and multiple pharmacological strategies have struggled to establish convincing benefit across PH-LHD populations.
PULSE-LHD therefore requires participants to have chronic heart failure despite maximally tolerated guideline-directed therapy and combined pre- and post-capillary pulmonary hypertension confirmed through right-heart catheterization. The study accommodates patients across reduced, mildly reduced and preserved ejection-fraction phenotypes rather than limiting the programme to one narrow type of heart failure.
Why is the primary endpoint more consequential than a walking-distance study?
PULSE-LHD’s primary efficacy endpoint is a time-to-first-event composite of cardiovascular death, heart transplantation or durable left-ventricular-assist-device implantation, heart-failure hospitalization and outpatient worsening heart-failure events. The principal safety endpoint examines device- or procedure-related major adverse events at 30 days.
That outcome design raises the evidentiary bar considerably. An intervention can improve pulmonary pressure or six-minute walk distance without necessarily reducing hospitalizations or preventing clinical deterioration. A major-heart-failure-event endpoint asks whether denervation changes the disease pathway enough to matter to the patient and health system rather than simply creating a favorable hemodynamic measurement.
The study’s estimated primary completion extends to the end of 2029, with overall completion expected later, so this is not a near-term readout. Control patients experiencing a primary efficacy event can potentially cross over at 24 months if they remain eligible, while randomized follow-up is scheduled at multiple points through 36 months.
What evidence already exists for PADN?
The strongest randomized published evidence has largely come from Group 1 pulmonary arterial hypertension rather than PH-LHD. In the sham-controlled PADN-CFDA study involving 128 patients with PAH, pulmonary artery denervation produced an adjusted 33.8-meter greater improvement in six-minute walk distance at six months than sham treatment. Pulmonary vascular resistance also fell more in the PADN group, and clinical worsening occurred in 1.6% of PADN-treated patients compared with 13.8% of controls during six-month follow-up.
Those results establish that catheter-based denervation can create measurable physiological and functional effects under randomized conditions, but they cannot be imported directly into Group 2 disease. Pulnovo itself explicitly warns that findings from previous studies, mainly in WHO Group 1 PH, have not been established in PH-LHD and are not predictive of PULSE-LHD outcomes.
The company has also generated early PH-LHD data outside the pivotal US programme, including the PADN-Columbus pilot presented in 2026, and plans additional data from a Chinese registration trial. Those programmes can strengthen the biological rationale, but PULSE-LHD is the trial positioned to answer the commercially decisive US question.
Why does CMS coverage matter before the device is approved?
CMS granted the study Category B IDE coverage in March 2026. Category B generally applies to investigational devices considered nonexperimental or investigational in the sense that certain underlying technologies or device types are sufficiently established for Medicare coverage of qualifying trial-related use, subject to applicable requirements. CMS approval does not mean the agency has concluded that PADN is clinically effective or guaranteed future reimbursement after commercialization.
It does, however, help the economics of running a 750-person randomized device study across US centers. Large invasive trials can be difficult to execute when hospitals must absorb substantial procedural and follow-up costs, so appropriate trial coverage can facilitate enrollment and participation.
The first two Henry Ford procedures therefore begin more than another catheter study. Pulnovo is testing whether a therapy initially developed around pulmonary vascular nerve modulation can produce hard heart-failure benefits in the dominant pulmonary-hypertension subtype. A positive result could expand PADN into a dramatically larger population; a neutral result would demonstrate why physiological improvements observed in Group 1 disease cannot automatically be translated into heart-failure-associated pulmonary hypertension.
