Recent advances in pre–procedural imaging have improved risk assessment and procedural planning for alcohol septal ablation (ASA) in patients with symptomatic obstructive hypertrophic cardiomyopathy (HOCM). However, limited data exist regarding the current practice and outcomes of ASA in Japan. Data from 634 patients who underwent ASA at 72 hospitals between January 2019 and December 2022 were extracted from the nationwide prospective J-SHD registry. Baseline characteristics, procedural details, and in-hospital outcomes were evaluated, and multivariate logistic regression analyses were performed to identify predictors of procedural success and complications. The cohort consisted predominantly of females (76.5%). The mean procedure time was 168 ± 52 minutes, and the mean alcohol volume injected was 3.0 ± 1.8 mL. Successful alcohol injection was achieved in 99.6% of cases, resulting in a significant reduction of the left ventricular outflow tract (LVOT) gradient from 72.0 ± 44.0 to 20.9 ± 24.6 mmHg (p <0.001). In-hospital mortality was 0.16%, while ventricular arrhythmia and high-grade heart block requiring permanent pacemaker implantation occurred in 0.63% and 7.9% of patients, respectively. A higher pre–procedural LVOT gradient predicted successful gradient reduction, whereas female sex independently predicted high-grade heart block. In conclusion, this nationwide registry demonstrated that ASA is a safe and effective therapy for HOCM in Japan. Female sex may represent a potential risk factor for conduction disturbances requiring pacemaker implantation.
Alcohol septal ablation (ASA) has become an established therapeutic option for patients with hypertrophic obstructive cardiomyopathy (HOCM) who are symptomatic despite optimal medical therapy and are not optimal surgical candidates. Over the past 2 decades, ASA has demonstrated significant efficacy in reducing left ventricular outflow tract (LVOT) gradients and improving functional capacity, with outcomes comparable to surgical myectomy in selected patients. , However, concerns remain regarding 1% to 2% of in-hospital death, 0.5% to 3% of ventricular arrhythmia including ventricular fibrillation, ,, 0.5% to 1.0% of catheter-related complications including access site bleeding and coronary artery dissection, , and 10% to 15% of complete heart block needing a permanent pacemaker. ,,,
Recent advancements in pre–procedural imaging have facilitated preoperative risk evaluation and procedural planning for ASA. For example, coronary computed tomography (CT) imaging is routinely used in Japan for understanding the dominant area of the target septal branch and the angle of bifurcation of the target septal branch from the coronary artery. This could lower the complications after ASA procedure. However, there are limited nationwide reports on the current status and outcomes of ASA across Japan.
Material and Methods
Database explanation
This study analyzed data collected from the Japanese Structural Heart Disease (J-SHD) registry spanning the years 2019 to 2022. The J-SHD is a prospective, nationwide, multicenter registry administered by the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT). , It systematically includes patients undergoing various structural heart disease interventions. Participation in the registry is mandatory for interventional cardiologists and affiliated cardiovascular institutions as part of the requirements for board certification and its renewal, thereby promoting comprehensive data collection. All ASA procedures performed in Japan are registered in the J-SHD registry.
Study participants, definitions, and clinical outcomes
This study included all ASA procedures performed in 72 hospitals across Japan between 2019 and 2022 since current collection format was established. We excluded patients if important variables were missing such as clinical outcomes. The following clinical variables were retrieved from the database: patients’ demographic information (age and sex); clinical status, as assessed by the New York Heart Association (NYHA) functional classification; and comorbidities, including diabetes mellitus, hypertension, chronic obstructive pulmonary disease (COPD), dyslipidemia, smoking history, renal insufficiency, maintenance dialysis, coronary artery disease, and cerebrovascular disease. Pre–procedural antithrombotic regimens were also recorded, encompassing aspirin, P2Y12 inhibitors, cilostazol, other antiplatelet agents, warfarin, and direct oral anticoagulants (DOACs). Additionally, procedural and anatomical parameters were also documented, such as procedure time, volume of contrast medium administered (mL), the amount of ethanol injection (mL), balloon size (mm), preprocedural and postprocedural LVOT gradient at rest (mmHg), length of hospitalization (only available in 2021 and 2022), and complications including in-hospital death, acute bleeding needing transfusion, access site complications, myocardial infarction, ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation), and advanced atrio-ventricular (AV) block needing permanent pacemaker implantation. Regarding LVOT gradient, the J-SHD does not collect pressure gradient during Valsalva maneuver, or maximum value during exercise.
Procedural success was defined as successful alcohol injection to the prespecified septal branch with more than 50% reduction of LVOT gradient. We hypothesized and explored that the volume of ethanol used was not only positively correlated with higher reduction in LVOT gradient but also associated with higher rate of complications such as ventricular arrhythmia and advanced atrio-ventricular block needing a permanent pacemaker implantation.
Ethical consideration
The study adhered to the ethical principles outlined in the Declaration of Helsinki and Japanese Ethical Guidelines for Medical and Health Research involving Human Subjects. Authorization for the use of data from the J-SHD registry was granted by an independent central ethics board under the Clinical Research Promotion Network Japan. Each participating center submitted documentation confirming compliance with consent procedures; however, in most cases, the requirement for written informed consent was waived due to the study’s observational design. All data were thoroughly anonymized prior to analysis.
Statistical analysis
Continuous variables are expressed as the mean and standard deviations and were compared using the t-tests. Categorical data are expressed as the number and percentage and were compared using the chi-square test or Fisher’s exact test. A time-trend analysis for yearly changes in procedural factors, complications, and outcomes was performed using the linear regression analysis for the continuous variables, the Cochran-Armitage trend test for binary variable, and ordinal variable for the Spearman’s correlation analysis. Multivariable logistic regression analyses were performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of advanced heart block requiring permanent pacemaker implantation. Statistical analyses were performed by a statistician (M. Takahara) using R version 4.1.1 (R Development Core Team, Vienna, Austria). p values of <0.05 were considered statistically significant.
Results
Patient characteristics
We firstly included all 681 cases of ASA procedures conducted in 118 hospitals across Japan between 2019 and 2022. We excluded 44 cases with an unknown outcome and 3 cases with an unknown amount of ethanol injection. Finally, we included 634 cases from 112 hospitals from all over Japan. A patient selection flowchart is presented in Figure 1 . The baseline characteristics of the study population are shown in Table 1 . In the J-SHD registry, the ASA procedure was constantly performed around 150 cases per year in all over Japan. Female patients consisted of 76.5% (485/634) of the whole population and were significantly older than male (73 ± 10 vs 66 ± 12 years, p <0.001). Almost 90% of the patients had NYHA II or III symptoms and took aspirin or P2Y12 inhibitors before the procedure.
Patient flow.
ASA = alcohol septal ablation.
Table 1
Patient Characteristics stratified by sex
| Variable |
Overall
(n = 634) |
Men
(n = 149) |
Women
(n = 485) |
p-value |
|---|---|---|---|---|
| Years | 0.65 | |||
| 2019 | 154 (24.3%) | 42 (28%) | 112 (23%) | |
| 2020 | 170 (26.8%) | 39 (26%) | 131 (27%) | |
| 2021 | 146 (23.0%) | 32 (21%) | 114 (24%) | |
| 2022 | 164 (25.9%) | 36 (24%) | 128 (26%) | |
| Age (mean ± standard deviation) | 71 ± 11 | 66 ± 12 | 73 ± 10 | <0.001 |
| NYHA functional class | (n = 629) | (n = 148) | (n = 481) | 0.64 |
| I | 37 (5.9%) | 10 (7%) | 27 (6%) | |
| II | 330 (52.5%) | 82 (55%) | 248 (52%) | |
| III | 239 (38.0%) | 50 (34%) | 189 (39%) | |
| IV | 23 (3.7%) | 6 (4%) | 17 (4%) | |
| Comorbidities | ||||
| Smoking | 72 (11.4%) | 30 (20%) | 42 (9%) | <0.001 |
| Hypertension | 386 (60.9%) | 78 (52%) | 308 (64%) | 0.016 |
| Dyslipidemia | 269 (42.4%) | 56 (38%) | 213 (44%) | 0.19 |
| Diabetes mellitus | 77 (12.1%) | 14 (9%) | 63 (13%) | 0.31 |
| Chronic renal failure | 98 (15.5%) | 22 (15%) | 76 (16%) | 0.90 |
| Coronary artery disease | 44 (6.9%) | 12 (8%) | 32 (7%) | 0.58 |
| Cerebrovascular disease | 16 (2.5%) | 1 (1%) | 15 (3%) | 0.14 |
| COPD | 17 (2.7%) | 6 (4%) | 11 (2%) | 0.25 |
| Medications | (n = 186) | (n = 42) | (n = 144) | |
| Aspirin | 137 (73.7%) | 31(74%) | 106 (74%) | >0.99 |
| P2Y12 inhibitors | 31 (16.7%) | 6 (14%) | 25 (17%) | 0.81 |
| Cilostazol | 4 (2.2%) | 1 (2%) | 3 (2%) | >0.99 |
| Other antiplatelets | 7 (3.8%) | 3 (7%) | 4 (3%) | 0.19 |
| Warfarin | 5 (2.7%) | 1 (2%) | 4 (3%) | >0.99 |
| Direct oral anticoagulants | 34 (18.3%) | 9 (21%) | 25 (17%) | 0.65 |
Data are presented as number (%) of patients and mean with standard deviation.
NYHA = New York Heart Association; COPD = chronic obstructive pulmonary disease.
Procedure details and clinical outcomes
Table 2 shows the procedure details and outcomes of this study. There were no significant differences between the groups in terms of balloon size, volume of ethanol used, contrast volume, and procedure time. Successful alcohol injection to the prespecified septal branch was achieved in 99.6% (629/634) of the patients. Female patients had significantly higher pre–procedural LVOT gradient (75.4 ± 44.7 mmHg vs 60.7 ± 39.7 mmHg [p <0.001]). ASA had significantly reduced LVOT gradient from 72.0 ± 44.0 to 20.9 ± 24.6 mmHg (p <0.001) and there were no differences in post–procedural LVOT gradient between men and women (p = 0.36). More than three-fourths of the patients gained procedural success. Scatter plots of pre– and post–procedural LVOT gradients are shown in Figure 2 .
Table 2
Procedure details and outcomes
| Variable |
Overall
(n = 634) |
Men
(n = 149) |
Women
(n = 485) |
p-value |
|---|---|---|---|---|
| Procedure | ||||
| Balloon size used (mm) | 1.9 ± 1.4 | 1.9 ± 1.1 | 1.9 ± 1.4 | 0.57 |
| Volume of ethanol used (mL) | 3.0 ± 1.8 | 3.2 ± 1.9 | 3.0 ± 1.8 | 0.28 |
| Contrast volume (mL) | 135 ± 67 | 134 ± 74 | 135 ± 65 | 0.86 |
| Fluoroscopy time (min) |
38 ± 25
(n = 538) |
37 ± 24
(n = 127) |
39 ± 25
(n = 411) |
0.54 |
| Procedure time (min) |
168 ± 52
(n = 382) |
164 ± 48
(n = 90) |
169 ± 53
(n = 292) |
0.41 |
| Outcomes | ||||
| Successful alcohol injection to the prespecified septal branch, n (%) | 629 (99.2%) | 148 (99%) | 481 (99%) | >0.99 |
|
LVOT gradient
(preprocedure, mmHg) |
72.0 ± 44.0 | 60.7 ± 39.7 | 75.4 ± 44.7 | <0.001 |
|
LVOT gradient
(postprocedure, mmHg) |
20.9 ± 24.6 | 19.2 ± 26.1 | 21.4 ± 24.1 | 0.36 |
| Gradient reduction (mmHg) | 66.3 ± 38.7 | 65.3 ± 43.6 | 66.6 ± 37.1 | 0.73 |
| Procedural success, n (%) | 494 (77.9%) | 115 (77%) | 379 (78%) | 0.82 |
| Complications | ||||
| In-hospital death, n (%) | 1 (0.2%) | 0 (0%) | 1 (0%) | >0.99 |
|
Permanent pacemaker implantation,
n (%) |
50 (7.9%) | 5 (3%) | 45 (9%) | 0.022 |
|
Acute arrhythmic events (VT/VF),
n (%) |
4 (0.6%) | 2 (1%) | 2 (0%) | 0.24 |
| Unintentional ethanol injection into non-target vessels, n (%) | 3 (0.5%) | 1 (1%) | 2 (0%) | 0.55 |
| Major bleeding or intracranial hemorrhage requiring transfusion/hemostasis, n (%) | 2 (0.3%) | 0 (0%) | 2 (0%) | >0.99 |
|
Emergency surgical intervention,
n (%) |
0 (0.0%) | 0 (0%) | 0 (0%) | >0.99 |
| Peripheral embolism, n (%) | 0 (0.0%) | 0 (0%) | 0 (0%) | >0.99 |
| Vascular rupture, n (%) | 0 (0.0%) | 0 (0%) | 0 (0%) | >0.99 |
| Acute vessel occlusion, n (%) | 0 (0.0%) | 0 (0%) | 0 (0%) | >0.99 |
| Contrast-induced nephropathy, n (%) | 1 (0.2%) | 0 (0%) | 1 (0%) | >0.99 |
| Other minor complications, n (%) | 30 (4.7%) | 3 (2%) | 27 (6%) | 0.080 |
| Length of hospital stay | (n = 310) | (n = 68) | (n = 242) | 0.17 |
| – ≤7 days, n (%) | 48 (15.5%) | 10 (15%) | 38 (16%) | |
| – 8 to 14 days, n (%) | 182 (58.7%) | 46 (68%) | 136 (56%) | |
| – ≥15 days, n (%) | 80 (25.8%) | 12 (18%) | 68 (28%) |
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