This study evaluated the prevalence of HCM in Japan using, for the first time, payer claims data from insurers. The DeSC and JMDC databases provided payer claims data from three insurers (AEMSS, Kokuho, and Kempo) covering approximately 14.6 million people in 2021. Based on these insurance data, the estimated number of patients with HCM in Japan in 2021 was 142,115. This is higher than the previously reported estimate of 52,000 in 2020, which was based on DPC hospital databases only [6]. It is worth noting that, in the current study, data from hospitals and clinics were included for each insurer, with almost 50% of the patients being diagnosed with HCM at clinics, which would account for the difference between the current and previously estimated number of patients with HCM.

The overall estimated prevalence of HCM in Japan slightly increased between 2018 and 2019, and this increase corresponds to the release of the Japanese guidelines for the diagnosis management of HCM [3]. The release of the guidelines could have led to an increase in awareness of correct diagnosis of HCM and, therefore, contributed to a rise in the prevalence of this disease. Additionally, the standardized annual prevalence of HCM in Japan over the study period (from 9.3 per 10,000 people in 2017 to 11.1 per 10,000 people in 2021) was comparable to those reported in Germany for the period 2011–2019 (9.75 per 10,000) and in the US in 2019 (8.00 per 10,000) but higher than the mean annual prevalence of HCM in the UK for the period 2009–2020 (4.15 per 10,000) [5, 7]. Although the studies in Germany, Japan, the UK, and the US all used diagnosis codes to estimate the prevalence of diagnosed HCM, it is possible that the lower prevalence in the UK could be due to differences in coding practices. It is also possible that differences in the age distribution or frequency of echocardiogram testing could contribute to the variation in the estimated prevalence. Both Japan and Germany have higher proportions of people over 50 years old than the UK and, although patients can receive a diagnosis of HCM at any age, the majority often receive a diagnosis in their fifties [8, 14,15,16,17].

Generally, the prevalence of HCM was higher in older patients. A similar trend was reported in the US and in Australia [18, 19]. The increase in prevalence with older age groups could be due to a greater likelihood of diagnosis, as older patients tend to be seen by doctors more frequently. It is also possible that some patients may have clinically silent HCM and that over time, environmental and genetic factors contribute to the development of symptoms at a later age [20,21,22]. Some pathogenic gene variants have also been linked to later onset of disease, such as variants in the genes encoding α-cardiac myosin heavy chain, cardiac myosin binding protein-C, and troponin I [20, 21]. Because older patients tend to have more comorbidities than younger patients, it is possible that impaired renal and hepatic function may be more common. Indeed, in this study, there was a higher prevalence of chronic kidney disease among patients in AEMSS (an older population) compared with Kokuho and Kempo. This may impact treatment strategies in this population. For example, treatments used to protect renal function, such as diuretics, are known to worsen symptoms of LVOT obstruction. Therefore, additional caution must be exercised when prescribing treatment in this patient population. The proportion of women with an HCM diagnosis also increased with age. These findings are similar to those reported in a community-based Japanese population, in which women were more likely than men to receive a diagnosis at an age of over 65 years [23]. The increase in prevalence with age in women could potential be linked to changes in estrogen levels associated with menopause [24]. Estrogen levels have been shown to affect cardiac function, with estrogen deficiency being linked to fibrosis, myocardial hypertrophy and impaired ventricular relaxation [24,25,26]. Therefore, menopause-induced reductions in estrogen levels may worsen symptoms associated with HCM, potentially leading to an increase in diagnosis. Further research into the potential impact of changes to estrogen levels on HCM disease progression and symptoms is required and may provide additional insights into sex-related differences in HCM.

The sensitivity analysis in this study suggested that the majority of younger patients with HCM (aged under 75 years) compared with patients aged at least 75 years attended medical institutions only once per year or less. This could imply that the majority of younger patients with an HCM diagnosis decided to take a ‘watch and wait’ approach, potentially because there was no specific treatment for HCM. Younger patients may also have fewer comorbidities and, therefore, may be less likely than older patients to attend medical institutions throughout the year.

According to the J-HCM registry, a large-scale registry survey of patients throughout Japan, 36% of patients with HCM had LVOT obstruction [27]. In the present study, a smaller proportion of patients had obstructive HCM diagnosed; however, most patients with HCM were categorized using a disease code that did not specify the subtype (code: 8846101). It is expected that a proportion of the patients with unspecified HCM would have obstructive HCM. The proportion of patients with obstructive HCM was similar across the three databases. There was a higher prevalence of obstructive HCM in the older age categories, and for those insured by AEMSS and Kokuho, a higher proportion of women than men had obstructive HCM. This could be due to a combination of factors: for example, it has been reported that female patients have a smaller left ventricular capacity size than male patients and they are more likely to have systolic anterior motion, both of which increase the likelihood of obstruction [23, 28, 29]. The presence of hypertrophy at the base of the interventricular septum (known as a sigmoid septum) is also more common in older people [30] and can contribute to LVOT obstruction [31, 32].

Commonly reported comorbidities in patients with HCM often include heart failure, atrial fibrillation, and arrhythmias [4, 33]. Yet, the present findings indicate that the most common comorbidities in Japanese patients with HCM were hypertension and heart failure. Indeed, the proportions of patients with heart failure and patients with hypertension in this study were higher than those reported in the general Japanese population, which were 5.3% and 20.9%, respectively [11]. Nevertheless, arrhythmia was reported in over a third of the study population, which is higher than that reported in the general Japanese population (0.76%) [34]. The proportion of patients with arrhythmia was similar across the three insurers; this is unlike other comorbidities, in which the proportion of patients tended to be highest in those insured by AEMSS (which represents an older population). Patients with an underlying genetic cause for HCM are often diagnosed at a younger age and are at risk of sudden cardiac death due to ventricular tachyarrhythmia and younger onset of symptoms [35]. Because the population covered by Kempo is younger than that covered by either of the other two insurers, it is possible that a higher proportion of patients with HCM with an underlying genetic cause to their disease are covered by this insurer than by the other two insurers. As such, this could be an explanation for why the prevalence of arrhythmias in Kempo data is similar to that found in the older AEMSS and Kokuho populations. Atrial fibrillation was reported in 18–40% of patients across the insurers, which is a similar range to that reported in patients with HCM across other studies but higher than the proportion reported in the general population (0.56%) [36, 37]. However, it is possible that paroxysmal atrial fibrillation is more likely to be diagnosed in patients with HCM compared with the general population owing to the increased monitoring of these patients, which may partly contribute to the higher prevalence. The proportion of patients with atrial fibrillation was highest in those covered by AEMSS (which insures an older population). This finding is in line with results from the Kochi RYOMA study, which reported that the prevalence of atrial fibrillation increased with age [33].

The Japanese treatment guidelines for HCM provide different treatment recommendations depending on HCM subtype [3]. Because the majority of patients in the present study had received a diagnosis of HCM with an unspecified subtype, it was not possible to assess the differences in treatment patterns between obstructive and nonobstructive HCM. Therefore, the treatment patterns reported in the study represented the treatments across multiple HCM subtypes. This is highlighted by the fact that the most common treatments received by the patients were beta-blockers, DHP calcium channel blockers, and ARBs. Indeed, the Japanese guidelines recommend the use of beta-blockers for treating obstructive, nonobstructive, and the dilated phase of HCM, and ARBs for the treatment of nonobstructive HCM and the dilated phase of HCM [3]. Overall the high use of beta-blockers for the treatment of HCM was similar to that reported in the Japan Medical Data Vision database [6]. In the US, claim database studies also reported a similar proportion of patients receiving beta blockers in patients with obstructive HCM [38, 39]. The Japanese guidelines recommend lipid-soluble β1 selective beta-blocker (e.g., bisoprolol) for the treatment of HCM, and approximately two-thirds of patients with obstructive HCM were receiving such treatment (bisoprolol) [3]. However, approximately a fifth of patients with obstructive HCM were receiving carvedilol, a beta-blocker with α-blocking action, which is not recommended for the treatment of HCM [3]. The high proportion of patients receiving carvedilol may be due to a lack of awareness of the HCM treatment guidelines and may have been prescribed for the treatment of heart failure, for rate-control of atrial fibrillation, or following a myocardial infarction [40, 41]. DHP calcium channel blockers and ARBs were also frequently prescribed for patients with obstructive HCM despite the Japanese guidelines recommending that these should be avoided [3]. Importantly, DHP calcium channel blockers, and ARBs can be used for the treatment of hypertension [42], which was the most prevalent comorbidity among patients with HCM. Therefore, it is possible that these drugs were prescribed to treat hypertension rather than HCM. The rate of sodium channel blocker use in patients with obstructive HCM was also similar to that previously reported in Japan (29.5%) [6].

Mental health disorders were present in 11–22% of patients across the three insurers in 2021. The prevalence of mental health disorders in patients with HCM in this study was higher than the 12‑month prevalences previously reported by the first and second World Mental Health Japan surveys (5.6% and 5.2%, respectively), which were community-based mental health epidemiological surveys of the general population [43, 44]. This finding is consistent with results from a Korean database study, which reported that in the first 12 months after HCM diagnosis, patients were at greater risk of developing mental health disorders such as anxiety, stress-related disorders, mood disorders, and somatoform disorders [45]. Similar findings were also reported in a small-scale study in the UK [46]. In a study using concept elicitation interviews, patients with HCM frequently reported that thinking about their disease made them feel anxious or depressed [47]. These results highlight the significant mental health burden associated with HCM. Additionally, a study in China indicated that patients with HCM and anxiety were at greater risk of sudden cardiac death and HCM-related heart failure events particularly when patients also experienced depression, compared with those without anxiety or depression [48]. This highlights a medical unmet need in these patients to reduce anxiety and depression to improve prognosis. Additional research is required to understand the impact of mental health disorders on the long-term outcomes of patients with HCM in Japan.

In 2021, only a small proportion of patients with HCM covered by AEMSS or Kokuho received medical expense subsidies for designated intractable diseases. According to the Japanese intractable disease information center, 4201 patients with HCM received medical expense subsidies, which is approximately 3.1% of the estimated HCM population and similar to the proportion of patients who received medical expense subsidies reported in our study, although the time periods analyzed were slightly different [49]. The proportion of patients receiving medical expense subsidies for nonpharmacological treatments were also low in AEMSS and Kokuho, despite being often associated with the need for hospitalization and with high medical costs. This could possibly be explained by a lack of awareness of the medical expense subsidy system, a time-consuming application procedure, or a need to fulfill certain criteria to be able to claim medical expense subsidy. Greater awareness of the subsidies through increased distribution of information is needed to decrease the financial burden on patients with high medical costs. For some patients, treatment costs for HCM are currently relatively inexpensive and therefore medical expense subsidies are not necessarily required. As new technologies and treatments become available, the requirement for subsidy might become more frequent. This was previously observed among patients with ulcerative colitis. When new drugs became available for the treatment of this orphan disease, there was an increase in the number of patients receiving medical expense subsidies [50].

There are a few limitations to this study. First, owing to the nature of administrative claims data, there is a risk of using unspecified disease codes such as cardiomyopathy or unspecified HCM, and individual records may be segmented if there was a change of insurer. Patients with undiagnosed HCM or who have been misdiagnosed would not have been captured in this analysis due to the nature of claims data. Therefore, the prevalence of HCM reported here may be underestimated. To circumvent this issue, future studies could utilize diagnostic databases and clinical data to aid in identifying these patients. Second, echocardiographic data and laboratory test results are not available from AEMSS, Kokuho, and Kempo; therefore, the accuracy of the HCM diagnosis, severity, and subtype classification cannot be verified. Future studies should aim to incorporate clinical data sources to provide in-depth clinical insights of patients with HCM. Third, data on daily clinical habits, such as cardiac rehabilitation were not captured in this study, and therefore, the impact on outcomes could not be assessed. Fourth, owing to data from other insurance groups not being available, Kempo data were applied to the missing population; however, the characteristics of the missing population may be different from those covered by Kempo. Fifth, welfare recipients (1.6% of the general population in Japan in 2021) were not included in the estimated prevalence [51]. It is, therefore, possible that patients with more severe disease are more likely to be counted in the welfare recipient population and that exclusion of this population could bias the study toward patients with less severe disease. Finally, claims data will only capture patients who interact with the healthcare system, therefore data on patients with milder disease may not be captured, potentially resulting in underestimation of disease prevalence.