To assess the impact of PADN combined with guideline-directed medical therapy (GDMT) versus a sham procedure with GDMT on clinical outcomes in heart failure (HF) patients with preserved left ventricular ejection fraction (LVEF\>40%). Outcomes include cardiovascular death, HF-related rehospitalization, requirement for heart transplantation or need of valvular treatment or LVAD or pacemaker implantation, and worsening in outpatients (defined as requirement for intravenous therapy or diuretic intensification, including increasing the types or dose of diuretics).
A randomized, multicenter, blinded, sham-controlled trial in Subjects with chronic HFpEF (LVEF \>40%) meeting inclusion criteria and no exclusion criterion will be enrolled from 25 + centers in China within 24 months. Patients will be randomized 1:1 to: * Experimental Group: PADN + GDMT * Control Group: Sham procedure + GDMT GDMT regimen: Sodium-glucose co-transporter 2 inhibitor (SGLT2i) + Spironolactone. SGLT2i can be dapagliflozin or empagliflozin. * Dapagliflozin: Target maintenance dose 10 mg/day. Contraindicated if eGFR persistently \<25 mL/min/1.73 m². * Empagliflozin: Target maintenance dose 10 mg/day. Contraindicated if eGFR persistently \<20 mL/min/1.73 m². * Spironolactone: Starting dose 10-20 mg/day, maximum dose 40 mg/day. Suspend if serum potassium is \>5.5 mmol/L; restart at half dose after correction. Permanently discontinue if serum potassium is \>6.0 mmol/L. Suspend and evaluate if eGFR persistently declines \>30% or \<30 mL/min/1.73 m². Other medications are left at the physician's discretion. The proportion of patients with persistent atrial fibrillation is not to exceed 35%.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
310
Advancing the pulmonary artery denervation catheter with a diameter to vessel of 1.1\~1.2:1 through the long sheath to the left pulmonary artery ostium. Connecting the catheter to the RF generator. Rotate the catheter under imaging so the premounted electrodes tightly contact the target ablation positions. Recommended temperature-controlled mode, set temperature to 50°C, ablation time to 150 seconds (with effective ablation time of 120 seconds, defined as the tissue temperature reaches 45°C-55°C. Ablation is performed at a total of 3 sites with 120 seconds for each.
The ablation catheter under imaging guidance will be advanced to the target ablation points, but DO NOT connect the ablation catheter to the RF generator; DO NOT deliver RF energy. The operator issues commands to "start" and "stop" RF ablation, simulating the sound of the PADN RF generator for at least 2 minutes (using a pre-recorded MP4).
GDMT regimen including sodium-glucose co-transporter 2 inhibitor (SGLT2i) + spironolactone. SGLT2i can be dapagliflozin or empagliflozin. * Dapagliflozin: Target maintenance dose 10 mg/day. Contraindicated if eGFR persistently \<25 mL/min/1.73 m². * Empagliflozin: Target maintenance dose 10 mg/day. Contraindicated if eGFR persistently \<20 mL/min/1.73 m². * Spironolactone: Starting dose 10-20 mg/day, maximum dose 40 mg/day. Suspend if serum potassium is \>5.5 mmol/L; restart at half dose after correction. Permanently discontinue if serum potassium is \>6.0 mmol/L. Suspend and evaluate if eGFR persistently declines \>30% or \<30 mL/min/1.73 m². Other medications are left at the physician's discretion.
Nanjing First Hospital, Nanjing Medical University
Nanjing, Jiangsu, China
Clinical worsening
A composite of clinical worsening at 12 months, including cardiovascular death, HF-related rehospitalization, requirement for heart transplantation, need of valvular treatment or LVAD or pacemaker implantation, and worsening in outpatients (defined as requirement for intravenous therapy or diuretic intensification, including increasing the types or dose of diuretics).
Time frame: From randomization to 12 months
Clinical worsening
A composite of clinical worsening at 24 months, including cardiovascular death, HF-related rehospitalization, requirement for heart transplantation, need of valvular treatment or LVAD or pacemaker implantation, and worsening in outpatients (defined as requirement for intravenous therapy or diuretic intensification, including increasing the types or dose of diuretics).
Time frame: From baseline to 24 months
Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS)
The Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) is a percentage-based health index ranging from 0 to 100, where higher scores indicate better heart failure-related health status.
Time frame: From baseline to 12 months
N-terminal pro-B-type natriuretic peptide (NT-proBNP)
Change in NT-proBNP levels at 1 month, 6 months, and 12 months.
Time frame: From baseline to 1 month, 6 months, and 12 months
6-minute walk distance (6MWD)
The 6-minute walk test in patients with chronic heart failure is clinically graded as follows: A distance of less than 150 meters indicates severe heart failure with poor prognosis; 150 to 300 meters corresponds to moderate heart failure; 300 to 450 meters reflects mild heart failure; and a distance greater than 450 meters suggests near-normal cardiac function and a relatively better clinical status.
Time frame: From baseline to 1 month, 6 months, and 12 months
KCCQ-CSS increase ≥6 points
The Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) is a percentage-based health index ranging from 0 to 100, where higher scores indicate better heart failure-related health status.
Time frame: From baseline to 12 months
NT-proBNP reduction ≥20%
Proportion of patients with NT-proBNP reduction ≥20% at 6, 12 months
Time frame: From baseline to 6 months and 12 months
KCCQ-CSS increase ≥6 points and NT-proBNP reduction ≥20%
KCCQ-CSS and NT-proBNP will be combined to report heart failure-related health status.
Time frame: From baseline to 6 months and 12 months
Echocardiographic parameters (chamber size, systolic and diastolic function)
Echocardiographic parameters, such as left ventricular ejection fraction (LVEF), ventricular volumes, and diastolic function indices (e.g., E/e' ratio), serve as key quantitative endpoints to evaluate cardiac remodeling and therapeutic response.
Time frame: From baseline to 6 months
Rate of worsening in outpatients
requiring intravenous injection of medicines, or needing diuretic intensification (including increase in types or doses of diuretics).
Time frame: Within 12 months
Rate of heart or lung transplantation
For patients with progressive heart failure
Time frame: within 12 months
Rate of left ventricular assist device implantation
Incidence of left ventricular assist device (LVAD) implantation, defined as the proportion of patients undergoing LVAD surgery during the study follow-up period.
Time frame: Within 12 months
Requirement of pacemaker / physiologic pacing / CRT / ICD/valvular treatment
Indications for pacemaker: Symptomatic sinus node dysfunction, High-grade AV block (Mobitz II or complete heart block), and Post-TAVI or post-MI advanced conduction disease when persistent. Indications for CRT: LVEF ≤35%, Sinus rhythm, LBBB morphology, QRS ≥150 ms, NYHA II-III or ambulatory IV, or others (determined by EP team). Indications for valvular treatment: Aortic Stenosis (AS), Aortic Regurgitation (AR) with Symptoms or Asymptomatic but LVEF ≤55% and/or progressive LV dilation, Primary (degenerative) Mitral Regurgitation (MR) Symptoms or LV dysfunction developing (LVEF ≤60%, Tricuspid Regurgitation (TR), Mitral Stenosis (MS), or others.
Time frame: Within 12 months
All events within 24 months
All patients will be followed-up until 24 months
Time frame: Within 24 months
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