Alcohol septal ablation for hypertrophic obstructive cardiomyopathy comparative therapies

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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]

Comparative therapies

Treatment options for symptomatic obstructive hypertrophic cardiomyopathy include conventional negative-inotropic therapy, cardiac myosin inhibitors, surgical septal myectomy, alcohol septal ablation (ASA), and investigational septal ablation techniques. Selection should integrate symptom burden, response to medical therapy, anatomy, age, comorbidities, procedural risk, anticipated treatment duration, access to an experienced HCM center, and patient preference.

Guideline positioning

The 2024 AHA/ACC multisociety guideline recommends a stepwise approach:

  • First-line therapy consists of a nonvasodilating beta blocker or a nondihydropyridine calcium channel blocker such as verapamil or diltiazem.
  • For persistent symptoms attributable to left ventricular outflow tract obstruction (LVOTO), parallel Class 1 options include an adult cardiac myosin inhibitor, disopyramide with an atrioventricular nodal blocking agent, or septal reduction therapy (SRT) at an experienced center.
  • Selection among these options should use shared decision-making rather than a uniform sequence for every patient.[1][2]
2024 AHA/ACC recommendations relevant to comparative therapy selection
Clinical setting Recommendation Class and level of evidence
Persistent symptoms despite guideline-directed medical therapy SRT with surgical myectomy or ASA at an experienced HCM center is recommended. Class 1, B-NR
Concomitant anomalous papillary muscle, intrinsic mitral valve disease, multivessel coronary artery disease, valvular aortic stenosis, or another cardiac disorder requiring surgery Surgical myectomy is recommended as part of the operative strategy. Class 1, B-NR
Severely symptomatic adult in whom surgery is contraindicated or carries unacceptable risk because of advanced age or serious comorbidity ASA is recommended when technically feasible. Class 1, C-LD
Appropriate SRT candidate who prefers a definitive procedure rather than further medical escalation SRT may be considered after shared decision-making. Class 2b, C-LD
NYHA class II symptoms with selected adverse clinical features Earlier surgical myectomy at a comprehensive HCM center may be considered when there is severe and progressive pulmonary hypertension attributable to LVOTO, left atrial enlargement with symptomatic atrial fibrillation, poor functional capacity on exercise testing, or a very high resting LVOT gradient (>100 mm Hg) in a child or young adult. Class 2b
Asymptomatic patient with normal exercise capacity SRT should not be performed. Class 3: Harm
Isolated treatment of LVOTO when conventional SRT is feasible Mitral valve replacement should not be performed solely to relieve LVOTO. Class 3: Harm

The 2023 European guideline assigned mavacamten a Class 2a position as add-on therapy or monotherapy when conventional first-line agents are contraindicated, whereas the 2024 AHA/ACC guideline placed an adult cardiac myosin inhibitor among the Class 1 options for persistent symptoms.[2]

Comparative treatment framework

Therapy Principal advantages Principal limitations Circumstances favoring use
Surgical myectomy Most complete and immediate gradient relief; broadest anatomic applicability; permits correction of mitral, papillary muscle, coronary, and other surgical pathology Sternotomy and cardiopulmonary bypass; longer recovery; PPM benchmark ≤5% at experienced centers but substantially higher with pre-existing right bundle branch block Younger or lower-risk surgical candidates; very marked hypertrophy or gradients; complex subvalvular anatomy; concomitant cardiac surgical indication
ASA Percutaneous, avoids sternotomy, shorter recovery, durable structural gradient reduction Dependent on suitable septal perforator anatomy; PPM benchmark ≤10%; less complete gradient relief and more reintervention than myectomy Older adults; frailty, comorbidity, or elevated surgical risk; suitable coronary anatomy; preference for a nonsurgical definitive intervention
Cardiac myosin inhibitor Noninvasive; reduces LVOT gradient and symptoms; may defer or prevent SRT Continuous therapy and echocardiographic monitoring; potential left ventricular ejection fraction suppression; drug interactions and access or cost considerations Adults preferring pharmacologic therapy; patients wishing to defer SRT; patients without an immediate surgical indication
Conventional negative-inotropic therapy Established first-line treatment; noninvasive; broadly available Variable symptom and gradient response; does not provide permanent anatomic relief Initial treatment of symptomatic obstruction and background therapy before second-line treatment
Percutaneous radiofrequency septal ablation Does not require a suitable septal perforator artery Investigational; limited comparative evidence; uncertain long-term safety and durability Clinical investigation or highly selected patients at expert centers

ASA versus surgical myectomy

No randomized trial has compared ASA with myectomy. Available comparisons are observational and subject to confounding by indication because patients selected for ASA are generally older and have more comorbidities.[1][3]

Comparative efficacy

Both procedures provide substantial symptomatic improvement, but myectomy produces more complete and immediate gradient elimination. In a propensity-matched cohort, the median predischarge resting LVOT gradient was 0 mm Hg after myectomy compared with 21 mm Hg after ASA. Clinical success after expert surgical myectomy is approximately 90%–95%.[1]

Myectomy can relieve obstruction at different ventricular levels and simultaneously correct anomalous papillary muscles, elongated mitral leaflets, intrinsic mitral valve disease, and other surgically treatable pathology. ASA cannot directly correct these abnormalities.[1][4]

Comparative safety and recovery

The 2024 guideline defines the following benchmark outcomes for experienced HCM centers:[1]

Benchmark outcome Surgical myectomy ASA
30-day mortality ≤1% ≤1%
Symptomatic improvement >90% >90%
Permanent pacemaker implantation ≤5% ≤10%

These are institutional performance benchmarks rather than uniform patient-level risks. Published PPM rates after myectomy range from approximately 2%–10%, and baseline conduction disease materially changes risk.[5] In a large myectomy series, pre-existing right bundle branch block was associated with complete heart block requiring PPM in approximately 34.8%, despite substantially lower risk in patients without baseline conduction disease.[6]

ASA avoids sternotomy and generally permits a shorter hospital stay and faster recovery. Its approximately 10% PPM benchmark should therefore be compared with the individual patient's conduction-modified surgical risk rather than with an assumed uniform myectomy risk below 5%.[1][6]

Reintervention and survival

Reintervention is substantially more frequent after ASA. A meta-analysis of 27 studies involving 15,968 patients found a reoperation hazard ratio of 9.14 (95% CI 6.55–12.75) favoring myectomy.[3]

Five-year survival appears similar, but longer-term observational data favor myectomy. A multicenter study of 3,859 patients reported 10-year all-cause mortality of 26.1% after ASA compared with 8.2% after myectomy, with an adjusted hazard ratio of 1.68 (95% CI 1.29–2.19).[7] The mortality difference was most pronounced among patients with NYHA class IV symptoms.[7]

In the meta-analysis, overall all-cause mortality did not differ significantly, but the subgroup of studies with at least 5 years of follow-up showed higher mortality after ASA (hazard ratio 1.50; 95% CI 1.04–2.15). This subgroup result is hypothesis-generating because the comparison is nonrandomized and ASA recipients were generally older and higher risk.[3]

Observational data in patients older than 65 years support favorable survival after expert septal reduction therapy, but do not eliminate treatment-selection bias.[8] A propensity-matched comparison in patients aged 75 years or older found similar long-term survival after ASA and myectomy, supporting ASA as a reasonable option when age-related surgical risk is elevated.[9]

ASA versus cardiac myosin inhibitors

No trial has directly randomized patients to ASA versus mavacamten or aficamten. Myosin-inhibitor trials demonstrate pharmacologic reduction of LVOT obstruction and SRT eligibility but do not establish comparative superiority over ASA or myectomy.

Mavacamten

In EXPLORER-HCM, mavacamten improved peak oxygen uptake and NYHA functional class compared with placebo. Resting and post-exercise LVOT gradients decreased by 37% and 42%, respectively. The 2024 guideline reports left ventricular ejection fraction below 50% attributable solely to mavacamten in approximately 5.7%, increasing to approximately 7%–10% when extenuating clinical factors are included.[10][1]

VALOR-HCM enrolled patients already referred for SRT:

  • At 16 weeks, 77% of placebo recipients remained guideline-eligible for SRT compared with 18% of mavacamten recipients.[11]
  • At 128 weeks, 15.7% met the composite SRT endpoint, corresponding to approximately 84% remaining free from that endpoint; gradient and symptom improvements were sustained among patients continuing treatment.[12]

MAVA-LTE extension data support sustained symptomatic and echocardiographic benefit with continued mavacamten during longer-term follow-up, while reinforcing the need for ongoing surveillance of left ventricular systolic function.[13]

Mavacamten generally requires continued therapy, REMS enrollment, and echocardiographic monitoring because of the risk of left ventricular systolic dysfunction. Its effect is pharmacologically reversible, unlike the permanent septal remodeling produced by ASA or myectomy.[1][10]

Aficamten

Aficamten provides another pharmacologic alternative to SRT:

  • In SEQUOIA-HCM, aficamten improved peak oxygen uptake, NYHA class, health status, LVOT gradients, and NT-proBNP compared with placebo. Transient left ventricular ejection fraction below 50% occurred in 3.5%.[14]
  • In MAPLE-HCM, aficamten monotherapy was superior to metoprolol monotherapy for peak oxygen uptake, with a between-group difference of 2.3 mL/kg/min, and also improved NYHA class, health status, Valsalva LVOT gradient, NT-proBNP, and left atrial volume index.[15]
  • A multidomain MAPLE-HCM analysis classified 78% of aficamten recipients as positive or complete responders compared with 3% of metoprolol recipients.[16]

Aficamten has a shorter half-life than mavacamten, allowing faster titration and washout and fewer drug–drug interactions.[10] Aficamten received FDA approval for symptomatic obstructive HCM in 2025.[17]

Key distinctions from ASA

  • ASA is a one-time invasive intervention intended to provide permanent structural gradient reduction; myosin inhibitors are noninvasive but generally require continuous therapy to sustain benefit.
  • ASA carries procedural risks, particularly conduction block and pacemaker implantation; myosin inhibitors carry risks of left ventricular ejection fraction suppression and require serial echocardiographic monitoring.
  • ASA requires suitable septal perforator anatomy; myosin-inhibitor efficacy is not dependent on coronary anatomy.
  • Myosin inhibitors cannot correct intrinsic mitral valve, papillary muscle, coronary, or valvular surgical pathology.
  • Myosin inhibitors entail recurring medication and monitoring requirements, whereas ASA concentrates resource use around a procedure but may incur subsequent costs from PPM implantation or reintervention.
  • Long-term comparative data between ASA and either myosin inhibitor are unavailable.[1][11][12]


ASA versus conventional medical therapy

Beta blockers and nondihydropyridine calcium channel blockers remain guideline-recommended first-line therapies. They may improve exertional symptoms by reducing heart rate and contractility but do not provide permanent anatomic relief of LVOTO.[1][18]

Disopyramide is a second-line negative-inotropic option, used with an atrioventricular nodal blocking agent. It avoids an invasive procedure but has variable efficacy and clinically important anticholinergic adverse effects.[1][18]

No randomized trial has directly compared ASA with beta blockers, calcium channel blockers, or disopyramide. The guideline generally recommends SRT for persistent symptoms despite medical therapy, while permitting SRT as an alternative to further medical escalation in an appropriate candidate after shared decision-making.[1]

Emerging percutaneous alternatives

Percutaneous intramyocardial septal radiofrequency ablation and related endocardial radiofrequency septal ablation techniques deliver thermal energy directly to the hypertrophied septum and do not require a suitable septal perforator artery.

In a comparative study of 145 patients, percutaneous endocardial septal radiofrequency ablation produced smaller improvements than ASA in NYHA class (−0.7 versus −1.4), septal thickness (−2.1 versus −4.5 mm), and LVOT gradient (−23.0 versus −51.1 mm Hg). Bundle branch block occurred less frequently with radiofrequency ablation, while reintervention and the composite of reintervention or rehospitalization were similar.[19]

Radiofrequency septal ablation remains investigational, is not included in current guideline treatment algorithms, and lacks established long-term safety and durability data.

Shared decision-making

  • Favor surgical myectomy when the patient has a concomitant cardiac surgical indication, complex mitral or papillary muscle anatomy, very marked hypertrophy or LVOT gradients, or when the priority is the most complete gradient elimination and lowest reintervention risk.[1][4]
  • Favor ASA when an adult has unacceptable surgical risk because of age or serious comorbidity, prefers a percutaneous definitive intervention, and has suitable septal coronary anatomy.[1]
  • Favor a cardiac myosin inhibitor when an adult prefers noninvasive treatment and accepts continuous therapy, medication interactions, serial imaging, and the possibility of left ventricular ejection fraction suppression.[1][12]
  • Continue conventional medical therapy when symptoms and gradients are adequately controlled or when procedural and myosin-inhibitor options are unsuitable.
  • All SRT decisions should be reviewed by a multidisciplinary HCM team at an experienced center.[1][8]

Evidence limitations

  • No randomized trial directly compares ASA with myectomy.
  • No randomized trial compares ASA or myectomy with a cardiac myosin inhibitor.
  • Observational ASA–myectomy survival comparisons remain vulnerable to confounding by indication.
  • The optimal sequencing of myosin inhibitors and SRT is unresolved.
  • Direct comparative cost-effectiveness evidence is limited.
  • Radiofrequency septal ablation lacks guideline endorsement and long-term comparative data.

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 Ommen SR, Ho CY, Asif IM; et al. (2024). "2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy". Journal of the American College of Cardiology. 83 (23): 2324–2405. doi:10.1016/j.jacc.2024.02.014.
  2. ↑ 2.0 2.1 Coylewright M, Cibotti-Sun M, Moore MM (2024). "2024 Hypertrophic Cardiomyopathy Guideline-at-a-Glance". Journal of the American College of Cardiology. 83 (23): 2406–2410. doi:10.1016/j.jacc.2024.04.002. PMID 38727648 Check |pmid= value (help).
  3. ↑ 3.0 3.1 3.2 Yokoyama Y, Shimoda T, Shimada YJ; et al. (2023). "Alcohol Septal Ablation Versus Surgical Septal Myectomy of Obstructive Hypertrophic Cardiomyopathy: Systematic Review and Meta-Analysis". European Journal of Cardio-Thoracic Surgery. 63 (3): ezad043. doi:10.1093/ejcts/ezad043. PMID 36782361 Check |pmid= value (help).
  4. ↑ 4.0 4.1 Maron BJ, Desai MY, Nishimura RA; et al. (2022). "Management of Hypertrophic Cardiomyopathy: JACC State-of-the-Art Review". Journal of the American College of Cardiology. 79 (4): 390–414. doi:10.1016/j.jacc.2021.11.021. PMID 35086661 Check |pmid= value (help).
  5. ↑ 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". Journal of the American College of Cardiology. 74 (7): e51–e156. doi:10.1016/j.jacc.2018.10.044.
  6. ↑ 6.0 6.1 Cui H, Schaff HV, Nishimura RA; et al. (2019). "Conduction Abnormalities and Long-Term Mortality Following Septal Myectomy in Patients With Obstructive Hypertrophic Cardiomyopathy". Journal of the American College of Cardiology. 74 (5): 645–655. doi:10.1016/j.jacc.2019.05.053. PMID 31370956.
  7. ↑ 7.0 7.1 Cui H, Schaff HV, Wang S; et al. (2022). "Survival Following Alcohol Septal Ablation or Septal Myectomy for Patients With Obstructive Hypertrophic Cardiomyopathy". Journal of the American College of Cardiology. 79 (17): 1647–1655. doi:10.1016/j.jacc.2022.02.032. PMID 35483751 Check |pmid= value (help).
  8. ↑ 8.0 8.1 Mentias A, Smedira NG, Krishnaswamy A; et al. (2023). "Survival After Septal Reduction in Patients Older Than 65 Years With Obstructive Hypertrophic Cardiomyopathy". Journal of the American College of Cardiology. 81 (2): 105–115. doi:10.1016/j.jacc.2022.10.027. PMID 36631204 Check |pmid= value (help).
  9. ↑ Sawma T, Schaff HV, Danesh S; et al. (2026). "Outcomes of Alcohol Septal Ablation vs Transaortic Septal Myectomy in Elderly Patients With Obstructive Hypertrophic Cardiomyopathy". JACC: Advances. 5 (1): 102488. doi:10.1016/j.jacadv.2025.102488. PMID 41609286 Check |pmid= value (help).
  10. ↑ 10.0 10.1 10.2 Braunwald E (2025). "Hypertrophic Cardiomyopathy". The New England Journal of Medicine. 393 (10): 1004–1015. doi:10.1056/NEJMra2413445.
  11. ↑ 11.0 11.1 Desai MY, Owens A, Geske JB; et al. (2022). "Myosin Inhibition in Patients With Obstructive Hypertrophic Cardiomyopathy Referred for Septal Reduction Therapy". Journal of the American College of Cardiology. 80 (2): 95–108. doi:10.1016/j.jacc.2022.04.048. PMID 35798455 Check |pmid= value (help).
  12. ↑ 12.0 12.1 12.2 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. ↑ Rader F, Oręziak A, Choudhury L; et al. (2024). "Mavacamten Treatment for Symptomatic Obstructive Hypertrophic Cardiomyopathy: Interim Results From the MAVA-LTE Study, EXPLORER-LTE Cohort". JACC: Heart Failure. 12 (1): 164–177. doi:10.1016/j.jchf.2023.09.028. PMID 38176782 Check |pmid= value (help).
  14. ↑ Maron MS, Masri A, Nassif ME; et al. (2024). "Impact of Aficamten on Disease and Symptom Burden in Obstructive Hypertrophic Cardiomyopathy: Results From SEQUOIA-HCM". Journal of the American College of Cardiology. 84 (19): 1821–1831. doi:10.1016/j.jacc.2024.09.003. PMID 39352339 Check |pmid= value (help).
  15. ↑ Garcia-Pavia P, Maron MS, Masri A; et al. (2025). "Aficamten or Metoprolol Monotherapy for Obstructive Hypertrophic Cardiomyopathy". The New England Journal of Medicine. 393 (10): 949–960. doi:10.1056/NEJMoa2504654.
  16. ↑ Wang A, Garcia-Pavia P, Masri A; et al. (2026). "Aficamten in Obstructive Hypertrophic Cardiomyopathy: A Multidomain, Patient-Level Analysis of the MAPLE-HCM Trial". Journal of the American College of Cardiology. 87 (8): 1029–1042. doi:10.1016/j.jacc.2025.10.057. PMID 41348072 Check |pmid= value (help).
  17. ↑ Food and Drug Administration. FDA Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book
  18. ↑ 18.0 18.1 Ommen SR, Semsarian C (2021). "Hypertrophic Cardiomyopathy: A Practical Approach to Guideline-Directed Management". Lancet. 398 (10316): 2102–2108. doi:10.1016/S0140-6736(21)01205-8. PMID 34600606 Check |pmid= value (help).
  19. ↑ Tian A, Qiao S, Yuan J; et al. (2025). "Comparison of Percutaneous Endocardial Septal Radiofrequency Ablation With Alcohol Septal Ablation in Treating Hypertrophic Obstructive Cardiomyopathy". The Canadian Journal of Cardiology: S0828-282X(25)00338-1. doi:10.1016/j.cjca.2025.05.005. PMID 40379240 Check |pmid= value (help).


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