Alcohol septal ablation for hypertrophic obstructive cardiomyopathy indications and contraindications

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

Indications and Contraindications

Alcohol septal ablation (ASA) is an invasive septal reduction therapy (SRT) for selected adults with symptomatic obstructive hypertrophic cardiomyopathy (HCM). Candidacy requires clinical, hemodynamic, and anatomic eligibility, followed by selection of ASA over septal myectomy according to operative risk, associated cardiac disease, coronary anatomy, conduction status, center expertise, and informed patient preference.

General eligibility for septal reduction therapy

All three eligibility domains should be present before SRT is considered.[1]

Eligibility domain Required findings
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 everyday activity or quality of life despite optimal medical therapy. Eligibility also applies when otherwise appropriate medical therapy is limited by clinically important or intolerable adverse effects.[1]
Hemodynamic Dynamic left ventricular outflow tract (LVOT) peak gradient ≥50 mmHg at rest or with physiologic provocation, such as exercise or Valsalva, associated with septal hypertrophy and systolic anterior motion of the mitral valve.[1]
Anatomic Target anterior septal thickness sufficient for safe and effective septal reduction in the judgment of the operator. For ASA, an appropriate septal perforator must supply the basal septum at the systolic anterior motion–septal contact point.[1]

A hemodynamically significant gradient without limiting obstruction-related symptoms is not an indication for SRT. SRT is not recommended in asymptomatic patients with normal exercise capacity (Class 3: Harm, LOE C-LD).[1]

Guideline recommendations for invasive treatment

Class of recommendation Level of evidence Recommendation
1 B-NR SRT at an experienced HCM center is recommended for eligible patients with persistent symptoms despite guideline-directed medical therapy (GDMT) or clinically important intolerance of medical therapy.[1]
1 B-NR Surgical myectomy is recommended when associated cardiac disease requires surgical treatment, including intrinsic mitral valve disease, anomalous papillary muscles, a markedly elongated anterior mitral leaflet, multivessel coronary artery disease requiring bypass surgery, or valvular aortic stenosis.[1]
1 C-LD ASA at an experienced HCM center is recommended for severely symptomatic adults despite GDMT when surgery is contraindicated or the operative risk is considered unacceptable because of serious comorbidities or advanced age.[1]
2b B-NR Earlier surgical myectomy may be reasonable in selected patients with NYHA class II symptoms and progressive pulmonary hypertension, left atrial enlargement with atrial fibrillation, poor functional capacity on exercise testing, or in children and young adults with very high resting gradients. This recommendation applies to myectomy rather than ASA.[1]
2b C-LD SRT may be considered as an alternative to further escalation of medical therapy after shared decision-making.[1]
3: Harm C-LD SRT is not recommended in asymptomatic patients with normal exercise capacity.[1]
3: Harm B-NR Mitral valve replacement should not be performed solely to relieve LVOT obstruction when an appropriate septal reduction procedure is available.[1]

The broader Class 1, LOE B-NR recommendation applies to SRT generally and therefore includes ASA in appropriately selected patients at experienced HCM centers. The separate ASA-specific Class 1, LOE C-LD recommendation addresses the particular scenario in which surgery is contraindicated or carries unacceptable risk; it does not imply that ASA is guideline-supported only in that setting. The Class 2b, LOE C-LD recommendation also permits SRT, including ASA when anatomically appropriate, as an alternative to further escalation of medical therapy after shared decision-making.[1]

Throughout these recommendations, inadequate medical therapy includes both persistent obstruction-related symptoms despite treatment and clinically important intolerance of otherwise appropriate GDMT.[1]

Regulatory indication

The FDA-approved indication for dehydrated alcohol injection (Ablysinol) is induction of a controlled septal infarction to improve exercise capacity in adults with symptomatic obstructive HCM who are not candidates for surgical myectomy.[2] The regulatory indication should be applied together with guideline-based clinical, hemodynamic, and anatomic assessment.

Features supporting selection of ASA

ASA should be selected only after the patient has met general SRT eligibility criteria.

Selection factor Clinical implication
Advanced age or unacceptable operative risk ASA is favored when frailty, chronic lung disease, renal dysfunction, prior sternotomy, or another serious comorbidity makes surgery contraindicated or unacceptably risky.[1][3]
Suitable obstruction pattern The obstruction should be dynamic and predominantly basal subaortic, with a septal target corresponding to the systolic anterior motion–septal contact point.[4]
Suitable septal perforator anatomy Coronary angiography and myocardial contrast echocardiography must identify a perforator that selectively supplies the intended basal septal target without clinically important nontarget perfusion.[1][4]
No associated lesion requiring surgery ASA is appropriate only when mitral, subvalvular, coronary, aortic valve, or other structural disease does not require open surgical correction.[1][3]
Informed patient preference Preference for a less invasive approach and shorter recovery may support ASA after a complete discussion of medical therapy, myectomy, ASA, comparative risks, and the possibility of residual obstruction or repeat intervention.[3][5]

Lack of local access to myectomy should not by itself determine procedure choice. When only one SRT option is available locally, the patient should be informed of alternatives and offered referral to a comprehensive HCM center.[1]

Contraindications to ASA

Anatomic or clinical contraindications

Contraindication Rationale
No suitable septal perforator ASA cannot be performed safely or effectively when no perforator selectively supplies the basal septal segment responsible for systolic anterior motion–septal contact.[1][4]
Midventricular, apical, or unsuitable multilevel obstruction These obstruction patterns are not reliably treated through a basal septal perforator territory and generally require another therapeutic approach.[3]
Concomitant cardiac disease requiring surgery Intrinsic mitral valve disease, anomalous papillary muscles requiring resection, a markedly elongated anterior mitral leaflet, multivessel coronary artery disease requiring coronary artery bypass grafting, valvular aortic stenosis, or a subaortic membrane should be corrected surgically. Myectomy is the recommended SRT in this setting.[1][3]
Children and adolescents ASA should generally not be performed in pediatric patients because of limited lifetime safety data and concerns regarding permanent pacing, reintervention, and the long-term significance of an iatrogenic myocardial scar.[3]

Relative contraindications and unfavorable features

Feature Clinical significance
Pre-existing left bundle branch block ASA commonly produces right bundle branch block; pre-existing left bundle branch block therefore substantially increases the risk of complete atrioventricular block. Baseline bundle branch block and age ≥70 years have been associated with complete heart block after ASA.[6] Among reported series, permanent pacemaker implantation rates after ASA vary by age: approximately 4% in patients younger than 40 years, 9% in those aged 40–60 years, and 14% in those aged 60 years or older.[7][8]
Pre-existing right bundle branch block Right bundle branch block is not the characteristic ASA-specific conduction concern because ASA itself commonly produces right bundle branch block. It is nevertheless relevant when considering myectomy, which commonly produces left bundle branch block; pre-existing right bundle branch block may therefore increase the risk of complete block after surgery. Baseline conduction morphology should be incorporated into selection of either SRT.[9][10]
Extreme septal hypertrophy Septal thickness ≥30 mm is associated with less reliable gradient reduction and generally favors extended surgical myectomy.[1]
Very high resting LVOT gradient A resting gradient ≥100 mmHg is associated with less uniform relief after ASA and generally favors myectomy, particularly in younger patients with acceptable operative risk.[1]
Mild septal hypertrophy Results may be inconsistent when there is limited target septal tissue. The AHA/ACC guideline does not specify a universal minimum septal thickness; suitability remains dependent on the contact site, perfusion territory, and operator judgment.[1][3]
Young adulthood ASA is generally not preferred in young adults because of longer lifetime exposure to risks related to residual obstruction, reintervention, conduction disease, and iatrogenic scar. No evidence-based age cutoff is established.[1][3]

Pre-existing left bundle branch block is best treated as a relative contraindication or major risk modifier rather than a universally defined absolute contraindication. Some experts consider the predicted pacing risk sufficient to favor myectomy whenever surgical risk and anatomy are acceptable.[7]

Role of cardiac myosin inhibitors before ASA

Contemporary GDMT has expanded the treatment pathway before invasive SRT. The 2024 AHA/ACC guideline includes a cardiac myosin inhibitor among Class 1 second-line options, alongside disopyramide and SRT, for patients who remain symptomatic despite a nonvasodilating beta-blocker or a nondihydropyridine calcium channel blocker.[1]

Cardiac myosin inhibitors such as mavacamten and aficamten, when available and clinically appropriate, may reduce symptoms and LVOT gradients sufficiently to defer or avoid SRT.[11][5]

In VALOR-HCM, 18% of patients receiving mavacamten remained eligible for SRT at 16 weeks, compared with 77% receiving placebo. At 128 weeks, 15.7% had undergone SRT or remained guideline-eligible for SRT.[12]

A myosin inhibitor should therefore be considered before ASA when available and not contraindicated. However, SRT may still be selected instead of further medication escalation after shared decision-making, and intolerance of GDMT remains a valid reason to proceed to invasive treatment.[1]

Center requirements and shared decision-making

ASA should be performed at an experienced HCM center by an interventional team with established expertise in patient selection, myocardial contrast echocardiography, septal perforator intervention, and management of conduction complications.[1]

A volume-outcome relationship has been documented for ASA. Patients treated during a center's first 50 procedures had significantly lower odds of complete clinical and hemodynamic response (OR 0.49, 95% CI 0.34–0.71), and centers with more than 50 ASA procedures implanted fewer postprocedure pacemakers than less experienced centers (9% versus 15%).[13][7]

Shared decision-making should address:

  • The likelihood that symptoms are caused by LVOT obstruction
  • The suitability of coronary, septal, mitral, and subvalvular anatomy
  • The operative risk and any associated disease requiring surgery
  • Continued or escalated medical therapy, including cardiac myosin inhibition
  • The risks and limitations of ASA and myectomy
  • Baseline conduction disease and its differing implications for ASA and myectomy
  • Center and operator experience
  • The patient's preferences regarding invasiveness, recovery, and long-term risk

Insufficient evidence exists to recommend SRT solely to improve survival in an otherwise asymptomatic patient.[1]

The 2023 European Society of Cardiology Cardiomyopathies Guideline similarly supports ASA as an alternative to myectomy but specifies an interventricular septal thickness >16 mm. It rates mavacamten as Class IIa, compared with the AHA/ACC Class 1 recommendation for a cardiac myosin inhibitor as second-line therapy.[14]

Registry data indicate that ASA can achieve similar gradient reduction in selected patients with septal thickness ≤16 mm, although permanent pacemaker implantation may be more frequent. This supports individualized assessment rather than treating 16 mm as an absolute biological threshold.[15]

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 1.21 1.22 1.23 1.24 1.25 1.26 1.27 Ommen SR, Ho CY, Asif IM; et al. (2024). "2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines". J Am Coll Cardiol. 83 (23): 2324–2405. doi:10.1016/j.jacc.2024.02.014.
  2. ↑ Food and Drug Administration. Dehydrated Alcohol (Ablysinol) prescribing information. Updated January 5, 2026. DailyMed
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 Maron BJ, Desai MY, Nishimura RA; et al. (2022). "Management of Hypertrophic Cardiomyopathy: JACC State-of-the-Art Review". J Am Coll Cardiol. 79 (4): 390–414. doi:10.1016/j.jacc.2021.11.021. PMID 35086661 Check |pmid= value (help).
  4. ↑ 4.0 4.1 4.2 Bali AD, Malik A, Naidu SS (2024). "Treatment Strategies for Hypertrophic Cardiomyopathy: Alcohol Septal Ablation and Procedural Step-by-Step Technique". Am J Cardiol. 212S: S42–S52. doi:10.1016/j.amjcard.2023.10.064. PMID 38368036 Check |pmid= value (help).
  5. ↑ 5.0 5.1 Braunwald E (2025). "Hypertrophic Cardiomyopathy". N Engl J Med. 393 (10): 1004–1015. doi:10.1056/NEJMra2413445.
  6. ↑ El-Sabawi B, Nishimura RA, Barsness GW; et al. (2020). "Temporal Occurrence of Arrhythmic Complications After Alcohol Septal Ablation". Circ Cardiovasc Interv. 13 (2): e008540. doi:10.1161/CIRCINTERVENTIONS.119.008540. PMID 31973555.
  7. ↑ 7.0 7.1 7.2 Veselka J, Liebregts M, Cooper R; et al. (2022). "Outcomes of Patients With Hypertrophic Obstructive Cardiomyopathy and Pacemaker Implanted After Alcohol Septal Ablation". JACC Cardiovasc Interv. 15 (19): 1910–1917. doi:10.1016/j.jcin.2022.06.034. PMID 36202559 Check |pmid= value (help).
  8. ↑ Batzner A, Pfeiffer B, Neugebauer A; et al. (2018). "Survival After Alcohol Septal Ablation in Patients With Hypertrophic Obstructive Cardiomyopathy". J Am Coll Cardiol. 72 (24): 3087–3094. doi:10.1016/j.jacc.2018.09.064. PMID 30545446.
  9. ↑ Agarwal S, Tuzcu EM, Desai MY; et al. (2010). "Updated Meta-Analysis of Septal Alcohol Ablation Versus Myectomy for Hypertrophic Cardiomyopathy". J Am Coll Cardiol. 55 (8): 823–834. doi:10.1016/j.jacc.2009.09.047.
  10. ↑ Kusumoto FM, Schoenfeld MH, Barrett C; et al. (2019). "2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay". J Am Coll Cardiol. 74 (7): e51–e156. doi:10.1016/j.jacc.2018.10.044.
  11. ↑ Hegde SM, Claggett BL, Wang X; et al. (2024). "Impact of Aficamten on Echocardiographic Cardiac Structure and Function in Symptomatic Obstructive Hypertrophic Cardiomyopathy". J Am Coll Cardiol. 84 (19): 1789–1802. doi:10.1016/j.jacc.2024.08.002. PMID 39217556 Check |pmid= value (help).
  12. ↑ Desai MY, Wolski K, Owens A; et al. (2025). "Mavacamten in Patients With Hypertrophic Cardiomyopathy Referred for Septal Reduction: Week 128 Results From VALOR-HCM". Circulation. 151 (19): 1378–1390. doi:10.1161/CIRCULATIONAHA.124.072445. PMID 39556124 Check |pmid= value (help).
  13. ↑ Veselka J, Liebregts M, Cooper R; et al. (2025). "Impact of Centre Experience on Complete Clinical and Haemodynamic Response After Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy". Int J Cardiol: 133865. doi:10.1016/j.ijcard.2025.133865. PMID 40921283 Check |pmid= value (help).
  14. ↑ Coylewright M, Cibotti-Sun M, Moore MM (2024). "2024 Hypertrophic Cardiomyopathy Guideline-at-a-Glance". J Am Coll Cardiol. 83 (23): 2406–2410. doi:10.1016/j.jacc.2024.04.002.
  15. ↑ Veselka J, Faber L, Liebregts M; et al. (2019). "Short- and Long-Term Outcomes of Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy in Patients With Mild Left Ventricular Hypertrophy: A Propensity Score Matching Analysis". Eur Heart J. 40 (21): 1681–1687. doi:10.1093/eurheartj/ehz110.
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