Abstract
ABSTRACT
Background
The Japanese Hypertrophic Cardiomyopathy Registry Study was designed to provide comprehensive, real-world insights into the clinical characteristics and management of hypertrophic cardiomyopathy (HCM) in Japan.
Methods
This multicentre, prospective study enrolled consecutive patients with HCM from 24 referral hospitals across Japan starting in 2016. The baseline characteristics of 1485 patients enrolled by December 2019 are presented in this analysis.
Results
The median ages at registration and diagnosis were 69 and 60 years, respectively, with men accounting for 54% of the cohort. Familial HCM was confirmed in 18% of cases. Of the cohort, 36% had hypertrophic obstructive cardiomyopathy (HOCM), while 8% had mid-ventricular obstruction, 14% had apical HCM and 4% were in the end-stage phase. Atrial fibrillation was observed in 27% of patients, though the majority were asymptomatic or had mild symptoms at registration. Adverse outcomes included prior sustained ventricular tachycardia or fibrillation (6%), heart failure requiring hospitalisation (11%) and embolic events (5%). Defibrillator implantation was performed in 11% of patients. Differences in the defibrillator indications for primary prevention in the current three guidelines and status of defibrillator deployment at registration were clarified: the percentages of class IIa recommendation in the whole cohort and of patients with defibrillator implantation in class IIa were 22% and 19% in the Japanese guidelines, 4% and 39% in the European guidelines and 28% and 22% in the American guidelines, respectively. Beta blockers were prescribed to 90% of patients with HOCM, while 51% received cibenzoline. Septal reduction therapies were performed in 22% of patients with HOCM, with 6% undergoing surgical myectomy.
Conclusions
As the first large-scale, prospective HCM registry in Japan, this study provides valuable baseline data on the clinical characteristics and management of HCM. These findings will help address gaps between current practice and guideline recommendations, improving the care of patients with HCM.
Keywords: Cardiomyopathy, Hypertrophic; Cohort Studies
WHAT IS ALREADY KNOWN ON THIS TOPIC
There have been few prospective studies on contemporary profiles of patients with hypertrophic cardiomyopathy (HCM) in Japan.
HCM is a primary myocardial disorder with marked heterogeneity; its racial differences are poorly understood.
There are separate recommendations in current different guidelines regarding the deployment of an implantable cardioverter defibrillator (ICD) for primary prevention.
WHAT THIS STUDY ADDS
This study indicates baseline clinical data in the first large-scale, prospective registry of patients with HCM in Japan.
Compared with data from the registries conducted in Europe and America, age was older and rates of family histories of HCM and sudden cardiac death were low, while apical HCM was frequent in Japan.
Differences in the ICD indications for primary prevention in the three guidelines and status of defibrillator deployment at registration were clarified.
Regarding the management for obstructive HCM, cibenzoline was much more frequently used than disopyramide, and percutaneous transluminal septal myocardial ablation was performed more frequently than myectomy in Japan.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
The study provides real-world contemporary information on clinical features and management of HCM including potential gaps with existing recommendations.
This prospective cohort is expected to complete the follow-up period after 5 years with the hope of clarifying prognostic factors.
Introduction
Hypertrophic cardiomyopathy (HCM) is the most prevalent primary myocardial disorder with heterogeneous morphological, functional and clinical features.1 2 The HCM-related mortality rate has been improved by the establishment of therapeutic strategies including prevention of sudden cardiac death (SCD) and management for left ventricular outflow tract (LVOT) obstruction and atrial fibrillation (AF).3 However, there is still some disagreement regarding therapeutic strategies. For example, there are different recommendations in current guidelines regarding the deployment of an implantable cardioverter defibrillator (ICD) for primary prevention.4,6 One of the reasons for the disagreement is that there had been few studies on the clinical features and natural history of HCM in a prospectively assembled patient cohort.7,10 Furthermore, it is also considered that there are racial differences in the frequency and risk factors of SCD in HCM. Therefore, in 2016, we established a large-scale, prospective registration survey of patients with HCM throughout Japan, named Japanese Hypertrophic Cardiomyopathy (J-HCM) Registry Study, for the purpose of understanding contemporary clinical features and management patterns in patients with HCM in Japan. The prospective cohort was planned to be followed up for up to 5 years with the hope of clarifying prognostic factors in order to improve clinical management for patients with HCM.
Here, we present the baseline characteristics of patients with HCM and management of HCM at registration of the J-HCM Registry Study with focus on the current status of ICD implantation and treatment for LVOT obstruction.
Methods
Subjects
We established the J-HCM Registry Study consisting of 24 referral hospitals throughout Japan (online supplemental file 1). Patients with HCM who visited an outpatient clinic (first or regular visit) or were hospitalised in one of the hospitals and gave consent to enrolment in our registration study were registered from 2016. The registration of patients was completed in December 2019, and it was planned to follow the patients prospectively for 5 years. (A detailed study plan is shown in online supplemental file 1.) Finally, 1485 patients were registered. Data were collected using a web-based electronic case report form. The clinical diagnosis of HCM was based on echocardiographic demonstration of left ventricular hypertrophy (LVH) (maximum left ventricular (LV) wall thickness ≥15 mm, or ≥13 mm in family members with a known family history of HCM) in the absence of another cardiac or systemic disease that could produce hypertrophy of such magnitude (eg, arterial hypertension, aortic stenosis or storage disease).5 Patients with known phenocopies such as metabolic disease or syndromic causes of LVH were excluded from the study. Specifically, Anderson-Fabry disease and cardiac amyloidosis were excluded as much as possible using bone scintigraphy and blood examinations.
Clinical evaluation
Evaluation of patients included medical history, clinical examination, 12-lead electrocardiography (ECG), echocardiography and ambulatory 24-hour Holter ECG analysis (details of the clinical evaluation method are shown in online supplemental file 2).
Based on morphological and haemodynamic assessments by echocardiography, we divided the patients into the following five groups5: (1) hypertrophic obstructive cardiomyopathy (HOCM), (2) mid-ventricular obstruction (MVO), (3) end-stage HCM, (4) apical HCM and (5) hypertrophic non-obstructive cardiomyopathy (see online supplemental file 2 for details of the five groups definition).
In the current analysis of baseline characteristics, first, we compared the clinical features of patients with HCM with and without prior sustained ventricular tachycardia/ventricular fibrillation (VT/VF). Then, we evaluated indications of ICD and status of defibrillator deployment at registration. Indication of ICD implantation follows guidelines: 2018 Japanese Circulation Society (JCS)/Japanese Heart Failure Society (JHFS) guidelines,4 2023 European Society of Cardiology (ESC) guidelines5 and 2024 AHA/ACC/AMSSM/HRS/PACES/SCMR guidelines (as American Heart Association/American College of Cardiology (AHA/ACC) guidelines).6 In the current study, data for late gadolinium enhancement on cardiac magnetic resonance (CMR) imaging and abnormal blood pressure response during exercise could not be sufficiently collected and analysed, and they were therefore not used in the risk assessment. Finally, we focused on the clinical features of patients with HOCM and situations regarding treatment.
Data analysis
All data are expressed as mean±SD, median (IQR) or frequency (percentage). To compare differences between groups, Student’s t-test (if normally distributed) or the Mann-Whitney U test (non-normally distributed variables) for continuous variables and the χ2 test or Fisher’s exact test for categorical variables were used. There were several missing data, including echocardiographic subtype information not available for 12 patients. A probability value of <0.05 was considered significant. All statistical analyses were performed using SPSS V.21 (IBM).
Results
Baseline clinical characteristics at registration
The clinical characteristics of the 1485 patients with HCM at registration are shown in table 1. The median ages at registration and at diagnosis were 69.0 (58.0–76.0) and 60.0 (47.0–69.0) years, respectively, and 809 patients (54%) were men. The time interval between diagnosis and registration was 6.0 (2.0–12.0) years. Figure 1 shows the age distributions of the patients at registration and at diagnosis. 273 patients (18%) had familial HCM and 169 patients (11%) had a family history of SCD. Most of the patients were asymptomatic or mildly symptomatic at registration: 1393 patients (94%) were New York Heart Association (NYHA) functional class I or II. Of the 1485 patients, there were 530 (36%) in the HOCM group, 126 (8%) in the MVO group, 207 (14%) in the apical HCM group and 57 (4%) in the end-stage HCM group.
Table 1. Baseline clinical characteristics of patients with HCM at registration according to the presence or absence of prior sustained VT/VF events.
| Variable | Whole cohort n=1485 |
Presence of prior sustained VT/VF events n=85 |
Absence of prior sustained VT/VF events n=1400 |
P value |
|---|---|---|---|---|
| Age at registration, years | 69.0 (58.0–76.0) | 61.0 (45.0–73.0) | 68.0 (58.0–76.0) | <0.001 |
| Gender: male, n (%) | 809 (54) | 58 (68) | 751 (54) | 0.009 |
| Age at diagnosis (n=1332), years | 60.0 (47.0–69.0) | 49.5 (25.8–61.0) | 60.0 (48.0–69.0) | <0.001 |
| Family history of HCM, n (%) | 273 (18) | 25 (29) | 248 (18) | 0.007 |
| Family history of SCD, n (%) | 169 (11) | 11 (13) | 158 (11) | 0.641 |
| NYHA functional class (n=1477), n (%) | 0.135 | |||
| I | 795 (54) | 50 (59) | 745 (54) | |
| II | 598 (40) | 29 (34) | 569 (41) | |
| III | 81 (5) | 5 (6) | 76 (5) | |
| IV | 3 (0.2) | 1 (1) | 2 (0.1) | |
| Echocardiographic data at registration | ||||
| Subtype (n=1473), n (%) | <0.001 | |||
| HOCM | 530 (36) | 22 (26) | 508 (37) | |
| MVO | 126 (8) | 14 (16) | 112 (8) | |
| Apical HCM | 207 (14) | 6 (7) | 201 (14) | |
| End-stage HCM | 57 (4) | 15 (18) | 42 (3) | |
| HNCM | 553 (37) | 28 (33) | 525 (38) | |
| Presence of intra-LV obstruction, n (%) | 398 (27) | 18 (21) | 380 (28) | 0.220 |
| Maximum LV wall thickness, mm | 17.0 (15.0–19.0) | 17.0 (15.0–20.0) | 17.0 (15.0–19.0) | 0.698 |
| LV end-diastolic diameter, mm | 45.0 (41.0–49.0) | 46.5 (42.4–51.0) | 45.0 (41.0–49.0) | <0.001 |
| LV ejection fraction, % | 66.0 (61.0–72.0) | 61.0 (51.8–67.2) | 66.0 (61.3–72.0) | <0.001 |
| Left atrial diameter, mm | 42.0 (37.0–47.0) | 43.0 (39.1–48.8) | 42.0 (37.0–47.0) | 0.023 |
| Presence of apical aneurysm, n (%) | 77 (5) | 11 (13) | 66 (5) | 0.003 |
| HCM-related cardiovascular events | ||||
| History of sustained VT/VF, n (%) | 85 (6) | – | – | |
| History of heart failure hospitalisation, n (%) | 164 (11) | 13 (15) | 151 (11) | 0.198 |
| History of embolism, n (%) | 67 (5) | 4 (5) | 63 (5) | 0.791 |
| Documentation of NSVT, n (%) | 375 (25) | – | – | |
| Syncope, n (%) | 217 (15) | 58 (68) | 159 (11) | <0.001 |
| Documentation of AF (n=1477), n (%) | 0.036 | |||
| Paroxysmal AF | 232 (16) | 21 (25) | 211 (15) | |
| Persistent or permanent AF | 174 (12) | 12 (14) | 162 (12) | |
| Treatments | ||||
| Medications, n (%) | ||||
| No medications | 169 (11) | 1 (1) | 168 (12) | 0.002 |
| Beta blockers | 1072 (72) | 75 (88) | 997 (71) | <0.001 |
| Cibenzoline | 337 (23) | 9 (11) | 328 (23) | 0.006 |
| Disopyramide | 28 (2) | 1 (1) | 27 (2) | 1.000 |
| Amiodarone | 146 (9) | 48 (56) | 98 (7) | <0.001 |
| Diuretics | 288 (19%) | 27 (32%) | 261 (19%) | 0.003 |
| Anticoagulants | 403 (27%) | 43 (51%) | 360 (26%) | <0.001 |
| Invasive interventions, n (%) | ||||
| Defibrillator implantation | 162 (11) | 74 (87) | 88 (6) | <0.001 |
| PTSMA | 126 (8) | 4 (5) | 122 (9) | 0.198 |
| Myectomy | 38 (3) | 1 (1) | 37 (3) | 0.721 |
Data are shown as median (IQR) or number (per cent).
AF, atrial fibrillation; HCM, hypertrophic cardiomyopathy; HNCM, hypertrophic non-obstructive cardiomyopathy; HOCM, hypertrophic obstructive cardiomyopathy; LV, left ventricular; MVO, mid-ventricular obstruction; NSVT, non-sustained ventricular tachycardia; NYHA, New York Heart Association; PTSMA, percutaneous transluminal septal myocardial ablation; SCD, sudden cardiac death; VF, ventricular fibrillation; VT, ventricular tachycardia.
Figure 1. Age at registration. Number of patients (A). Age at diagnosis. Number of patients (B).
Regarding the HCM-related adverse events, prior sustained VT or VF occurred in 85 patients (6%) at registration, and 164 patients (11%) had heart failure requiring hospitalisation. At registration, 406 patients (27%) had documentation of AF, and non-sustained ventricular tachycardia (NSVT) was documented in 375 patients (25%).
Beta blockers were prescribed in 1072 patients (72%). With regard to invasive interventions, 162 patients (11%) received a defibrillator implantation: an ICD in 155 patients and a cardiac resynchronisation therapy defibrillator in seven patients. Percutaneous transluminal septal myocardial ablation (PTSMA) was performed in 126 patients (8%), and 38 patients (3%) had myectomy.
Clinical characteristics of patients with HCM with prior sustained VT/VF
Table 1 shows the clinical characteristics of patients with HCM at registration according to the presence or absence of prior sustained VT/VF events. Both at registration and diagnosis, patients with prior sustained VT/VF were younger than patients without prior sustained VT/VF. Both the percentage of men and the percentage of patients with a family history of HCM were higher in patients with prior sustained VT/VF. The percentage of patients with a family history of SCD did not differ between the two groups. There was no difference between the two groups in the NYHA functional class. Results of echocardiography showed that end-stage HCM was frequent and the number of patients with apical HCM was smaller in patients with sustained VT/VF. Although maximum LV wall thickness was not different between the two groups, significant differences were found between the two groups in LV ejection fraction, LV end-diastolic diameter, left atrial diameter and percentage of patients with apical aneurysm. The percentage of patients who had syncope was higher in the sustained VT/VF group. With regard to medications at registration, beta blockers, amiodarone, diuretics and anticoagulants were more frequently prescribed in patients with prior sustained VT/VF than in patients without VT/VF.
Indications of ICD and status of defibrillator deployment at registration
In 85 patients with prior sustained VT/VF at registration, 74 (87%) received defibrillator implantation as secondary prevention (table 1). Table 2 and figure 2 show indications of ICD for primary prevention according to the guidelines (2018 JCS/JHFS, 2023 ESC, 2024 AHA/ACC guidelines) in 1400 patients with HCM without prior sustained VT/VF at registration. Among the three HCM guidelines, different distributions of the number of classified patients were seen. In the group classified by the 2023 ESC, the percentage of class IIa was 4%. On the other hand, the percentages of class IIa in the 2018 JCS/JHFS and 2024 AHA/ACC guidelines were 22% and 28%, respectively.
Table 2. Indications of ICD for primary prevention according to the guidelines in 1400 patients with HCM without VT/VF and the status of defibrillator implantation at registration.
| 2018 JCS/JHFS | 2023 ESC | 2024 AHA/ACC | |
|---|---|---|---|
| Class IIa, n (%) | 311 (22) | 51 (4) | 386 (28) |
| Status of ICD implantation in class IIa, n (%) | 60 (19) | 20 (39) | 86 (22) |
| Class IIb, n (%) | 459 (33) | 116 (8) | 177 (13) |
| Status of ICD implantation in class IIb, n (%) | 23 (5) | 25 (22) | 1 (1) |
| Class III, n (%) | 630 (45) | 949 (68) | 837 (60) |
| Status of ICD implantation in class III, n (%) | 5 (1) | 32 (3) | 1 (0.1) |
| Patients with extreme characteristics | N/A | 243 (17%) | N/A |
| Status of ICD implantation in the above | – | 10 (4%) | – |
| Patients with deficient data | N/A | 41 (3%) | N/A |
| Status of ICD implantation in the above | – | 1 (2%) | – |
AHA/ACC, American Heart Association/American College of Cardiology; ESC, European Society of Cardiology; HCM, hypertrophic cardiomyopathy; ICD, implantable cardioverter defibrillator; JCS/JHFS, Japanese Circulation Society/Japanese Heart Failure Society; N/A, not applicable; VF, ventricular fibrillation; VT, ventricular tachycardia.
Figure 2. Indications of implantable cardioverter defibrillator (ICD) for primary prevention according to the guidelines and the status of defibrillator implantation at registration in each class. AHA/ACC, American Heart Association/American College of Cardiology; ESC, European Society of Cardiology; JCS/JHFS, Japanese Circulation Society/Japanese Heart Failure Society.
The status of defibrillator implantation at registration in each class is also shown in table 2 and figure 2. In 51 patients in class IIa judged by the 2023 ESC guidelines, 20 (39%) had defibrillator deployment. The percentages of patients with defibrillator implantation in class IIa in the 2018 JCS/JHFS and 2024 AHA/ACC guidelines were 19% and 22%, respectively.
Clinical characteristics of patients with HOCM and situations regarding treatment
The clinical characteristics at registration of patients with HOCM in comparison with the clinical characteristics of other patients are shown in table 3. The percentage of men was lower in the HOCM group. Patients with HOCM were older and included a higher percentage of symptomatic patients (NYHA≥II and syncope) and a lower percentage of patients with AF or NSVT. Echocardiographic data showed that LV end-diastolic diameter was smaller and LV ejection fraction was higher in the HOCM group. Both sustained VT/VF and embolic events occurred less frequently in patients with HOCM than in other patients, although there was no difference in prior heart failure events.
Table 3. Baseline clinical characteristics of patients with HCM at registration according to subtypes (HOCM vs others).
| HOCM n=530 |
Others n=943 |
P value | |
|---|---|---|---|
| Age at registration, years | 69.0 (59.3–76.0) | 68.0 (56.0–76.0) | 0.125 |
| Gender: male, n (%) | 197 (37) | 607 (64) | <0.001 |
| Age at diagnosis, years | 61.0 (50.0–70.0) | 59.0 (45.0–68.0) | <0.001 |
| Family history of HCM, n (%) | 85 (16) | 187 (20) | 0.072 |
| Family history of SCD, n (%) | 57 (11) | 112 (12) | 0.517 |
| NYHA functional class, n (%) | <0.001 | ||
| I | 216 (41) | 576 (61) | |
| II | 271 (51) | 326 (35) | |
| III | 43 (8) | 38 (4) | |
| IV | 0 (0) | 3 (0.3) | |
| Echocardiographic data at registration | |||
| Maximum LV wall thickness, mm | 17.0 (15.0–19.0) | 17.0 (15.0–19.0) | 0.705 |
| LV end-diastolic diameter, mm | 43.0 (39.0–46.0) | 46.2 (42.6–51.0) | <0.001 |
| LV ejection fraction, % | 68.0 (64.0–74.0) | 65.0 (60.0–71.0) | <0.001 |
| Left atrial diameter, mm | 42.0 (37.8–47.0) | 42.0 (37.0–48.0) | 0.273 |
| Presence of apical aneurysm, n (%) | 10 (2) | 67 (7) | <0.001 |
| HCM-related cardiovascular events | |||
| History of sustained VT/VF, n (%) | 22 (4) | 63 (7) | 0.046 |
| History of heart failure hospitalisation, n (%) | 57 (11) | 107 (11) | 0.729 |
| History of embolism, n (%) | 10 (2) | 57 (6) | <0.001 |
| Documentation of NSVT, n (%) | 99 (19) | 231 (24) | 0.010 |
| Syncope, n (%) | 96 (18%) | 120 (3%) | 0.005 |
| Documentation of AF, n (%) | 117 (22) | 289 (31) | <0.001 |
| Paroxysmal AF | 88 (17%) | 144 (15%) | |
| Persistent or permanent AF | 29 (5%) | 145 (15%) | |
| Treatments | |||
| Medications, n (%) | |||
| No medications | 16 (3) | 153 (16) | <0.001 |
| Beta blockers | 477 (90) | 592 (63) | <0.001 |
| Cibenzoline | 271 (51) | 63 (7) | <0.001 |
| Disopyramide | 23 (4) | 5 (1) | <0.001 |
| Amiodarone | 39 (7) | 107 (11) | 0.014 |
| Diuretics | 69 (13) | 219 (23) | <0.001 |
| Anticoagulants | 106 (20) | 297 (31) | <0.001 |
| Invasive interventions, n (%) | |||
| Defibrillator implantation | 46 (9) | 116 (12) | 0.033 |
Data are shown as median (IQR) or number (per cent).
AF, atrial fibrillation; HCM, hypertrophic cardiomyopathy; HOCM, hypertrophic obstructive cardiomyopathy; LV, left ventricular; NSVT, non-sustained ventricular tachycardia; NYHA, New York Heart Association; SCD, sudden cardiac death; VF, ventricular fibrillation; VT, ventricular tachycardia.
For treatment at registration, beta blockers, cibenzoline and disopyramide were more frequently prescribed in patients with HOCM (table 3). On the other hand, amiodarone, diuretics, anticoagulants and a defibrillator were used less in the HOCM group. In 530 patients with HOCM, 386 (73%) had oral medications only. Regarding septal reduction therapies, 114 patients (22%) received PTSMA and 33 patients (6%) received myectomy (including three patients who received both PTSMA and myectomy). Table 4 shows the status of LVOT obstruction at registration after oral medication and septal reduction therapies. In the whole HOCM population, 59% of the patients still showed a significant pressure gradient. On the other hand, 21% of the patients who received PTSMA had LVOT obstruction after PTSMA, and only 12% of the patients who received myectomy showed residual obstruction.
Table 4. Status of residual LVOT gradient ≥30 mm Hg at registration in patients with HOCM.
| Whole HOCM n=530 |
Medication only n=386 |
After PTSMA n=111 |
After myectomy n=33 |
|
|---|---|---|---|---|
| Percentage | 59 | 63 | 20 | 12 |
HOCM, hypertrophic obstructive cardiomyopathy; LVOT, left ventricular outflow tract; PTSMA, percutaneous transluminal septal myocardial ablation.
Comparison of the J-HCM Registry data with European and American prospective registry data
Table 5 shows the baseline characteristics of patients with HCM in the J-HCM Registry Study, EURObservational Research Programme (EORP) Cardiomyopathy Registry7 and the Hypertrophic Cardiomyopathy Registry (HCMR).8 In our Japanese cohort, ages at registration and at diagnosis were older, and rates of family histories of HCM and SCD were low. Although the prevalences of AF were similar (around 27%) in the J-HCM and EORP registries, severe functional disability (NYHA class III/IV) was less frequent in the Japanese cohort. Furthermore, the prevalence of prior sustained VT or VF seemed to be low in our HCM population. Regarding treatments, the percentages of patients receiving beta blockers were similar, but diuretics were used less frequently in the Japanese cohort. For device deployment, even taking into account the low frequency of a history of sustained VT/VF in Japan, the rate of defibrillator implantation seemed to be low. With regard to septal reduction therapies, myectomy was performed less in Japan. Compared with our data, patients in the HCMR appeared to have milder symptoms as judged by NYHA class and medical treatment.
Table 5. Baseline characteristics of patients with HCM in the J-HCM Registry, EORP Cardiomyopathy Registry and HCMR.
| J-HCM Registry n=1485 |
EORP Cardiomyopathy Registry n=1739 |
HCMR n=2755 |
|
|---|---|---|---|
| Age at registration, years | 69.0 | 55.0 | 49 |
| Gender: male, % | 54 | 59 | 71 |
| Age at diagnosis, years | 60.0 | 47.0 | NA |
| Family history of HCM, % | 18 | 49 | 34 |
| Family history of SCD, % | 11 | 21 | NA |
| NYHA functional class, % | |||
| I | 54 | 33 | 67 |
| II | 40 | 50 | 26 |
| III/IV | 6 | 17 | 7 |
| Documentation of AF, % | 27 | 27 | 12 |
| History of sustained VT/VF, % | 6 | 11 | NA |
| Treatments | |||
| Medications, % | |||
| Beta blockers | 72 | 74 | 57 |
| Diuretics | 19 | 31 | 12 |
| Anticoagulants | 27 | 27 | 9 |
| Invasive interventions, % | |||
| Defibrillator implantation | 11 | 20 | NA |
| PTSMA | 8 | 4 | NA |
| Myectomy | 3 | 5 | NA |
Data are shown as median or per cent.
AF, atrial fibrillation; EORP, EURObservational Research Programme; HCM, hypertrophic cardiomyopathy; HCMR, Hypertrophic Cardiomyopathy Registry; J-HCM, Japanese Hypertrophic Cardiomyopathy; NA, not available; NYHA, New York Heart Association; PTSMA, percutaneous transluminal septal myocardial ablation; SCD, sudden cardiac death; VF, ventricular fibrillation; VT, ventricular tachycardia.
Discussion
As the first large-scale, prospective HCM registry in Japan, this study provides valuable baseline data on the clinical characteristics and management of Japanese HCM. Notably, the study provided information on the implementation of guidelines for primary prevention of SCD and current situations regarding treatment for LVOT obstruction in different areas in Japan.
There have been few prospective observational studies on contemporary profiles and practical management of patients with HCM, particularly in Japan.7,10 When compared with data from the EORP registry,7 the first prospective multinational European registry on cardiomyopathies, and of the HCMR, the first prospective registry to identify novel prognostic markers using CMR imaging, we have a better understanding of the current situation of patients with HCM in Japan. The clinical differences between these three large prospective observational cohorts are likely to be due to various factors including the population of patients, ethnicities, healthcare systems and study designs. The age distribution of patients in the present study is probably due to the fact that Japan has one of the most aged populations in the world. The percentage of elderly people aged 65 years or over in Japan in 2022 was very high (29.9%), being the second-highest ratio after that in the Principality of Monaco. Another characteristic of the Japanese registry was that only 18% of the patients had proven familial HCM. One of the reasons for this low percentage may be that clinical evaluation of family members has not been conducted sufficiently, although the Japanese guidelines recommend assessing first-degree relatives as class I.4 Furthermore, as for HCM subtypes, a relatively large number of patients in our Japanese cohort had apical HCM, which is commonly seen in middle-aged and older men with little family history of HCM, as previously reported in Japan.11 12
We focused on indications of ICD for SCD prevention according to HCM guidelines. Of the 1485 patients, 85 (6%) had prior sustained VT/VF at registration and 74 (87%) received defibrillator implantation as secondary prevention. Regarding the indications of ICD for primary prevention among the three guidelines,4,6 the percentages of class IIa were 22%, 4% and 28% classified by the 2018 JCS/JHFS, 2023 ESC and 2024 AHA/ACC guidelines, respectively. Based on the distribution of ICD implantation classes, indications of ICD for primary prevention by the JCS/JHFS guidelines are located in the middle between those in Europe and the USA. Looking at the actual defibrillator implantation status for each class, the percentages of ICD deployment in class IIa were higher in the 2023 ESC guidelines. On the other hand, 3% of the patients even in class III in the 2014 ESC guidelines also had ICD implantation. In the 2024 AHA/ACC guidelines, the percentages of class IIa and class IIb were 28% and 13%, respectively, and of the 88 patients who had an ICD implanted for primary prevention, 98% had class IIa indications in our HCM population. Although the contents of these three guidelines are different, the Japanese guidelines already included the high-risk group of the ESC guidelines as class IIa indications. In clinical practice in Japan, we also refer to the contents of the AHA guidelines with a shared decision-making process. In the 5-year follow-up period in the J-HCM Registry, we plan to evaluate the indications for ICD implantation according to each of the guidelines and to identify prognostic factors and their combinations for SCD when the follow-up period ends at the end of 2024, which are expected to enable more precise risk stratification for prevention of SCD in Japanese patients with HCM. Considering the possibility of racial differences in the frequency and risk factors of SCD, it is not surprising that risk strategies differ from those overseas, and we believe that this prospective registry study in Japan will lead to valuable results.
Regarding the management for LVOT obstruction, larger percentages of patients with HOCM were symptomatic and had prescriptions for medications such as beta blockers, cibenzoline and disopyramide than patients with other types of HCM. It is characterised by the fact that cibenzoline,13,15 a drug that is expected to have effects similar to those of disopyramide and milder anticholinergic side effects, was much more frequently used than disopyramide in Japan. Another characteristic of the treatment in our cohort was that PTSMA was performed more frequently than myectomy. On the other hand, the responses to treatments including medication with beta blockers or cibenzoline and septal reduction therapies with PTSMA or myectomy seemed to be consistent with the data from Western countries.16 17 Through the 5-year follow-up period until the end of 2024, it will be interesting to know the prognosis depending on whether the pressure gradient of the LV outflow tract remains or not. Under these circumstances, we have entered an exciting era in which we can use a new therapeutic drug mavacamten, a first-in-class myosin inhibitor, to target the hypercontractile phenotype of HCM.18 19 This drug has been used in Western countries, and it is expected to be available for HOCM treatment in Japan. When verifying the mid-term to long-term effects of mavacamten in the future, we believe that our prospective registry study will be important to examine the natural history of Japanese patients with HOCM with current treatment without the use of mavacamten.
Limitations
There were several limitations in this study. First, there may still be some bias, although this study was a prospective registration study and we enrolled as many consenting consecutive patients as possible. Since many university hospitals participated in this registry, there might be selected referral patterns skewed towards high-risk patients. In addition, some hospitals have a high volume of referral patients for invasive treatments for HOCM, which might lead to higher frequency of HOCM than in the general practice in Japan. Second, data for late gadolinium enhancement of CMR imaging, which has recently come to be used as a risk factor for SCD in patients with HCM,20 21 were not used in the analysis of ICD indications for primary prevention. In the near future, we plan to analyse the data of ICD indications based on the additional CMR findings. Third, because the Japanese guidelines were published in the middle of the registration period in this study,4 it is possible that the contents of the current guidelines were not reflected in the management of HCM at the time of registration for this study. In this regard, clinical data are being collected every year to determine whether additional treatments or changes in management will occur during the 5-year follow-up period. Finally, genetic testing data were not available. Although the advantages of genetic diagnosis have been recognised in patients with HCM,10 22 23 clinical practice in Japan has not been proactive in identifying genetic variants that cause HCM. One of the main reasons for this was that genetic testing was not covered by insurance in Japan for a long time, and insurance for HCM was approved for the first time in April 2022.
Conclusions
As the first large-scale, prospective HCM registry throughout Japan, this study provides real-world contemporary information on clinical features and management of HCM. These findings will help address gaps between current practice and guideline recommendations, improving the care of patients with HCM.
Supplementary material
Footnotes
Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Provenance and peer review: Not commissioned; externally peer reviewed.
Patient consent for publication: Not applicable.
Ethics approval: This study involves human participants and was approved by the Ethics Committee on Medical Research of Kochi Medical School (reference number: ERB-104512), and informed consent was obtained from all patients or their parents in accordance with the guidelines of the Ethics Committee. Participants gave informed consent to participate in the study before taking part.
Patient and public involvement: Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.
Data availability statement
Data are available upon reasonable request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
Data are available upon reasonable request.