REFINE-HCM: Intramyocardial Septal Radiofrequency Ablation for Obstructive Hypertrophic Cardiomyopathy

A Prospective, Multicenter, Randomized, Parallel-Controlled Superiority Study Evaluating the Efficacy and Safety of a Transcatheter Intramyocardial Septal Radiofrequency Ablation System in Patients With Obstructive Hypertrophic Cardiomyopathy

This is a prospective, multicenter, randomized, parallel-controlled, superiority clinical trial designed to evaluate the efficacy and safety of a transcatheter intramyocardial septal radiofrequency ablation system for the treatment of patients with obstructive hypertrophic cardiomyopathy (oHCM). Eligible participants will be randomized in a 2:1 ratio to receive either active ablation under intracardiac echocardiographic guidance or a sham procedure. All participants will continue to receive standard-of-care medical therapy during the study period. The primary endpoint is the treatment effectiveness rate at 6 months, defined as a ≥50% reduction in LVOT gradient from baseline or a resting LVOT gradient <30 mmHg.

Inclusion Criteria:

• Age 18 to 80 years, regardless of sex
• Diagnosed with obstructive hypertrophic cardiomyopathy (oHCM)
• Presence of significant symptoms (e.g., dyspnea, chest pain, fatigue, palpitations, syncope)
• NYHA class II or higher with LVOTG ≥50 mmHg at rest or provoked (assessed by echocardiography)
• Septal thickness ≥15 mm
• Unsuitable for surgical myectomy or refusal of surgery
• Provided informed consent and agree to complete follow-up

Exclusion Criteria:

• Asymptomatic or non-obstructive HCM
• Septal thickness ≥30 mm
• Mitral valve anatomy not suitable for ablation as judged by investigator
• High risk of sudden cardiac death (SCD) requiring ICD implantation
• Complete right bundle branch block at screening
• Infective endocarditis, myocarditis, atrial myxoma, or intracardiac thrombus
• Contraindication to transseptal access (e.g., septal patch)
• Mechanical valves or history of aortic valve replacement
• Severe heart failure with persistent symptoms and LVEF <40%
• Major cardiac events within 6 months (e.g., cardiac arrest, MI, heart failure hospitalization)
• Significant structural heart disease requiring surgery
• Prior septal reduction therapy or pacemaker implantation
• Constrictive pericarditis or significant congenital heart disease
• Bleeding disorders or contraindication to antithrombotic therapy
• Liver dysfunction (ALT/AST >3× ULN)
• Renal insufficiency (creatinine >2.0 mg/dL or on dialysis)
• Pregnant, breastfeeding, or planning pregnancy within 6 months post-op
• Life expectancy <12 months
• Participation in other investigational studies within 30 days or 5 half-lives
• Investigator determines poor compliance or unsuitability
• Contraindications to cardiac MRI (e.g., ICD, allergy to contrast, claustrophobia)