Favorable Long-Term Outcomes After Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy in Japan

Hypertrophic cardiomyopathy (HCM) is a complex and relatively common genetic cardiac disease characterized by left or right ventricular hypertrophy, and left ventricular (LV) diastolic dysfunction based on cardiac hypertrophy. Approximately 30% of HCM patients have a significant LV pressure gradient (≥30 mmHg) at rest, and 60–70% of these patients are diagnosed with hypertrophic obstructive cardiomyopathy (HOCM) because an induced pressure gradient is also present. To relieve the LV outflow tract obstruction (LVOTO)-associated symptoms of HOCM patients, septal reduction therapy (SRT) is an effective option. SRT is a Class I indication for drug-refractory symptomatic HOCM with a LVOT gradient ≥50 mmHg, either at rest or after provocation.¹ SRT includes septal myectomy (SM) and alcohol septal ablation (ASA).²

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ASA was first introduced by Sigwart in 1995³ and then rapidly and widely spread because it is a less invasive procedure than SM. However, a concern was the uncertain long-term durability of ASA. To date, there has been no evidence of long-term efficacy of ASA in Japanese HOCM patients, although reports on the long-term outcomes after ASA in countries other than Japan revealed that the long-term mortality rate after ASA was comparable to the expected survival for an age- and sex- comparable general population.^4,5

In this issue of the Journal, Sawayama et al⁶ retrospectively investigate the long-term clinical outcomes after ASA for patients with HOCM at a single center in Japan. Their study revealed that the primary outcome (composite of cardiovascular death or hospitalization for heart failure) at 5 and 10 years was 16.5% and 25.6%, respectively, and all-cause death after ASA at 5 and 10 years was 15.1% and 28.9%, respectively, results that are comparable to those from previous foreign studies^4,7,8 (all-cause death at 5 and 10 years, 8–11%, 18–26%, respectively). Thus the present study is the first to elucidate the long-term efficacy of ASA for Japanese HOCM patients.⁶

Although ASA was reported to have inferior long-term clinical outcomes compared with SM,⁹ recent meta-analyses have shown comparable long-term mortality rates between ASA and SM.^10–12 Because of these now favorable outcomes and being a less invasive procedure, ASA has become the primary SRT modality in many centers in Europe.¹³ Despite the present study revealing favorable outcomes after ASA for Japanese HOCM patients, it should be noted that the incidence of both permanent pacemaker implantation and reintervention was higher after ASA than SM; 5 of 42 patients (11%) required permanent pacemaker implantation.⁶ Even though ASA showed a comparable long-term mortality rate to SM, the heart team should discuss which SRT is suitable for the individual patient (Table).¹⁴

Table.

Discussion Points for the Heart Team to Determine Which Procedure Should Be Selected

	ASA preferred	SM preferred
Age	>40 years	≥40 years
Concomitant heart disease requiring surgery	No	Yes
Abnormal papillary muscle	No	Yes
Apical aneurysm	No	Yes
Appropriate target branch	Yes	No
Surgical risk	Moderate or high	Low
Target myocardium to be ablated or resected	LVOT and/or mid ventricle	Including apical portion
Moderate-severe MR that cannot be corrected by SRT alone	No	Yes

ASA, alcohol septal ablation; LVOT, left ventricular outflow tract; MR, mitral regurgitation; SM, septal myectomy; SRT, septal reduction therapy.

Discovering the predictors of long-term adverse events after ASA and to improve the postprocedural prognosis is challenging. Sawayama et al also elucidate that moderate or severe mitral regurgitation (MR) after ASA was significantly associated with the primary outcome. According to their result of multivariate analysis, residual significant MR after ASA was associated with the primary outcome independently of the systolic anterior movement (SAM) grade after ASA. This result suggests that in these patients, the etiology of MR might not only be SAM-related. If there is significant MR before ASA, it is important to assess its etiology (i.e., SAM-related MR only or combined with degenerative MR, atrial MR, or mitral valve prolapse) and discuss if ASA would improve MR sufficiently. There are several other predictors of long-term all-cause death after ASA reported in previous studies. A large ASA registry in Europe, the Euro-ASA registry reported that age at ASA, septal thickness before ASA, NYHA class before ASA, and the LVOT gradient at the last check-up were independent predictors of all-cause death in long-term.⁷

Foreign institutes have recently reported further long-term outcomes after ASA (≤20–25 years) and they reveal favorable very long-term outcomes (≈30% of all-cause deaths at 20 years).^5,15 Longer and larger follow-up data in Japan is desired to definitively establish the efficacy of ASA.

References

• 1.   Kitaoka H, Tsutsui H, Kubo T, Ide T, Chikamori T, Fukuda K, et al. JCS/JHFS 2018 Guideline on the diagnosis and treatment of cardiomyopathies. Circ J 2021; 85: 1590–1689, doi:10.1253/circj.CJ-20-0910.
• 2.   Maekawa Y, Akita K, Takanashi S. Contemporary septal reduction therapy in drug-refractory hypertrophic obstructive cardiomyopathy. Circ J 2018; 82: 1977–1984, doi:10.1253/circj.CJ-18-0575.
• 3.   Sigwart U. Non-surgical myocardial reduction for hyoertrophic obstructive cardiomyopathy. Lancet 1995; 346: 211–214.
• 4.   Veselka J, Krejci J, Tomasov P, Zemanek D. Long-term survival after alcohol septal ablation for hypertrophic obstructive cardiomyopathy: A comparison with general population. Eur Heart J 2014; 35: 2040–2045, doi:10.1093/eurheartj/eht495.
• 5.   Karabulut U, Yilmaz Can Y, Duygu E, Karabulut D, Keskin K, Okay T. Periprocedural, short-term, and long-term outcomes of alcohol septal ablation in patients with hypertrophic obstructive cardiomyopathy: A 20-year single-center experience. Anatol J Cardiol 2022; 26: 316–324, doi:10.5152/AnatolJCardiol2022.852.
• 6.   Sawayama Y, Kubo S, Ohya M, Ono S, Tanaka H, Maruo T, et al. Long-term clinical outcome after alcohol septal ablation and its periprocedural predictive factors in Japan: A retrospective observational study. Circ J 2023, doi:10.1253/circj.CJ-23-0529.
• 7.   Veselka J, Jensen MK, Liebregts M, Januska J, Krejci J, Bartel T, et al. Long-term clinical outcome after alcohol septal ablation for obstructive hypertrophic cardiomyopathy: Results from the Euro-ASA registry. Eur Heart J 2016; 37: 1517–1523, doi:10.1093/eurheartj/ehv693.
• 8.   Cui H, Schaff HV, Wang S, Lahr BD, Rowin EJ, Rastegar H, et al. Survival following alcohol septal ablation or septal myectomy for patients with obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol 2022; 79: 1647–1655, doi:10.1016/j.jacc.2022.02.032.
• 9.   ten Cate FJ, Soliman OI, Michels M, Theuns DA, de Jong PL, Geleijnse ML, et al. Long-term outcome of alcohol septal ablation in patients with obstructive hypertrophic cardiomyopathy: A word of caution. Circ Heart Fail 2010; 3: 362–369, doi:10.1161/CIRCHEARTFAILURE.109.862359.
• 10.   Liebregts M, Vriesendorp PA, Mahmoodi BK, Schinkel AF, Michels M, ten Berg JM. A systematic review and meta-analysis of long-term outcomes after septal reduction therapy in patients with hypertrophic cardiomyopathy. JACC Heart Fail 2015; 3: 896–905, doi:10.1016/j.jchf.2015.06.011.
• 11.   Singh K, Qutub M, Carson K, Hibbert B, Glover C. A meta analysis of current status of alcohol septal ablation and surgical myectomy for obstructive hypertrophic cardiomyopathy. Catheter Cardiovasc Interv 2016; 88: 107–115, doi:10.1002/ccd.26293.
• 12.   Yokoyama Y, Shimoda T, Shimada YJ, Shimamura J, Akita K, Yasuda R, et al. Alcohol septal ablation versus surgical septal myectomy of obstructive hypertrophic cardiomyopathy: Systematic review and meta-analysis. Eur J Cardiothorac Surg 2023; 63: ezad043, doi:10.1093/ejcts/ezad043.
• 13.   Arbelo E, Protonotarios A, Gimeno JR, Arbustini E, Barriales-Villa R, Basso C, et al. 2023 ESC Guidelines for the management of cardiomyopathies. Eur Heart J 2023; 44: 3503–3626, doi:10.1093/eurheartj/ehad194.
• 14.   Imori Y, Takano H, Kitamura M, Aoyama R, Sangen H, Kenta O, et al. Percutaneous transluminal septal myocardial ablation for hypertrophic obstructive cardiomyopathy through non-left anterior descending septal perforators. Heart Vessels 2020; 35: 647–654, doi:10.1007/s00380-019-01525-8.
• 15.   Veselka J, Tesar D, Topalo R, Hansvenclova E, Adlova R. Follow-up of up to 25 years after alcohol septal ablation for obstructive hypertrophic cardiomyopathy. JACC Cardiovasc Interv 2023; 16: 1556–1557, doi:10.1016/j.jcin.2023.03.049.