Alcohol septal ablation for hypertrophic obstructive cardiomyopathy overview

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Nehal Eid, M.D.[2]

Overview

Definition

Alcohol septal ablation (ASA) is a percutaneous septal reduction therapy for selected adults with symptomatic obstructive hypertrophic cardiomyopathy (HCM). Targeted infusion of ethanol into an appropriate septal perforator branch produces a controlled, localized infarction of the basal interventricular septum. Subsequent septal akinesia, thinning, and remodeling widen the left ventricular outflow tract (LVOT), reduce systolic anterior motion of the mitral valve, and relieve dynamic LVOT obstruction.

Dynamic obstruction in HCM usually reflects interaction among basal septal hypertrophy, systolic anterior motion of the mitral valve, and secondary mitral regurgitation. Clinically important obstruction may cause exertional dyspnea, chest pain, presyncope, or syncope and can substantially impair functional capacity despite medical therapy.

Clinical eligibility framework

Candidates for septal reduction therapy generally fulfill all of the following domains:

• Clinical: Severe dyspnea or chest pain, usually NYHA functional class III–IV, or exertional syncope or near-syncope attributable to LVOT obstruction and interfering with daily activity despite guideline-directed medical therapy.
• Hemodynamic: Dynamic LVOT gradient ≥50 mm Hg at rest or with physiologic provocation, associated with septal hypertrophy and systolic anterior motion.
• Anatomic: Targeted anterior septal thickness sufficient to perform the procedure safely and effectively, without concomitant structural disease that is better corrected surgically.

Evaluation should be performed by a multidisciplinary HCM team and should confirm that symptoms are attributable to LVOT obstruction, medical therapy has been optimized, and the coronary and structural anatomy is suitable for ASA.

The literature demonstrates a volume–outcome relationship for both myectomy and ASA. Referral to comprehensive or primary HCM centers with demonstrated excellence in clinical outcomes is encouraged when septal reduction therapy is unavailable locally.

Guideline positioning

The 2024 AHA/ACC multisociety guideline places ASA within the following treatment framework:

• Initial therapy for symptomatic obstructive HCM consists of a nonvasodilating beta blocker or a nondihydropyridine calcium channel blocker.
• For symptoms persisting despite initial therapy, adding a cardiac myosin inhibitor in adults, disopyramide, or septal reduction therapy at an experienced HCM center represents a Class 1 escalation strategy.
• Septal reduction therapy with surgical myectomy or ASA is recommended for eligible patients with obstructive HCM whose symptoms persist despite medical therapy (Class 1, level of evidence B-NR).
• ASA is specifically recommended for severely symptomatic adults in whom surgery is contraindicated or carries unacceptable risk because of serious comorbidities or advanced age (Class 1, level of evidence C-LD).
• Septal reduction therapy may be considered as an alternative to further medical escalation after shared decision-making in selected patients (Class 2b, level of evidence C-LD).
• For patients with HCM who are asymptomatic and have normal exercise capacity, septal reduction therapy is not recommended (Class 3: Harm, level of evidence C-LD).
• For symptomatic patients with obstructive HCM in whom septal reduction therapy is an option, mitral valve replacement should not be performed solely to relieve LVOT obstruction (Class 3: Harm, level of evidence B-NR).

Surgical myectomy is generally preferred when concomitant surgery is required for intrinsic mitral valve disease, anomalous papillary muscles, multivessel coronary artery disease, or other surgically correctable structural abnormalities. It is also generally favored in children, younger patients, and patients with complex anatomy or extreme septal hypertrophy.

The guideline permits consideration of earlier myectomy in selected patients with NYHA functional class II symptoms and additional clinical factors, including progressive pulmonary hypertension attributable to LVOT obstruction or mitral regurgitation, left atrial enlargement with symptomatic atrial fibrillation, objectively poor functional capacity, or very high resting gradients in children and young adults (Class 2b). This is a myectomy-specific pathway and does not expand the indication for ASA.

Role relative to cardiac myosin inhibitors

Cardiac myosin inhibitors provide a noninvasive option that can reduce LVOT gradients and symptom burden and may defer or avoid septal reduction therapy in some patients. In VALOR-HCM, mavacamten reduced continued guideline eligibility for septal reduction from 77% with placebo to 18% among patients already referred for an invasive procedure.

Aficamten, a next-generation cardiac myosin inhibitor approved by the U.S. Food and Drug Administration in December 2025, improved peak oxygen uptake, LVOT gradients, and NYHA functional class in SEQUOIA-HCM.

Myosin-inhibitor therapy is an alternative escalation strategy rather than an obligatory prerequisite to ASA. Sequencing should incorporate anatomy, comorbidities, medication access and tolerance, patient preference, and local expertise.

Expected effects and principal limitations

In appropriately selected patients treated at experienced centers, ASA produces substantial and generally durable reductions in LVOT gradient and symptom burden. Unlike myectomy, the full effect is not immediate and continues to develop as the ablated septum remodels over subsequent months.

Important limitations include:

• Complete atrioventricular block requiring permanent pacemaker implantation, reported in approximately 10%–15% of patients.
• Residual or recurrent obstruction and a greater likelihood of repeat septal reduction than after myectomy.
• Dependence on favorable septal perforator anatomy and accurate localization of the target myocardium.
• Inability to correct concomitant mitral, papillary muscle, coronary, or other structural abnormalities requiring surgery.
• Creation of an iatrogenic septal scar; whether this independently increases long-term ventricular arrhythmic risk remains uncertain.

No randomized trial has directly compared ASA with surgical myectomy. Comparative evidence is predominantly observational and is affected by substantial selection differences because patients undergoing ASA are generally older and have more comorbidities. Consequently, treatment choice should be individualized through shared decision-making at an experienced HCM center.