Physical activity and quality of life in patients with hypertrophic cardiomyopathy in Japan: a quantitative study

ABSTRACT

Aim

To describe the burden of hypertrophic cardiomyopathy (HCM) using patient-reported outcome tools and a study-specific questionnaire.

Patients and methods

This two-phase, cross-sectional, non-interventional, observational study (qualitative [previous] and quantitative [current]) included adults with HCM and New York Heart Association functional classification 2/3 recruited from healthcare facilities across Japan. The International Physical Activity Questionnaire (IPAQ), Kansas City Cardiomyopathy Questionnaire (KCCQ), Hypertrophic Cardiomyopathy Symptom Questionnaire (HCMSQ), and Hospital Anxiety and Depression Scale (HADS) were used alongside a questionnaire developed using the qualitative findings.

Results

The analysis included 120 patients (mean age, 59.1 ± 16.3 years; 55.5% [66/120] male), 60 each with non-obstructive and obstructive HCM. Patients with (vs. without) lifestyle changes had lower median IPAQ score (495.0 [363.0–1803.5] vs. 990.0 [369.4–2295.0], p = 0.159) and KCCQ – Clinical Summary Score (81.3 [65.6–90.7] vs. 92.0 [81.4–97.9], p < 0.001), and higher HADS-Depression (5.0 [3.0–8.0] vs. 2.0 [1.0–6.0], p = 0.001) and HCMSQ-shortness of breath (5.0 [2.0–6.0] vs. 3.0 [0.0–4.5], p < 0.001) scores. Most patients (83.9%) noticed HCM symptoms, and some patients attributed symptoms to causes other than HCM. Most patients (89.0%) told others about their HCM. Primary care physicians were the main information source (99.2%).

Conclusions

In this quantitative analysis, HCM affected patients’ lifestyles and physical activity.

Clinical trial registration

NCT06181617 (ClinicalTrials.gov).

PLAIN LANGUAGE SUMMARY

What is this article about?

This article is about patients with hypertrophic cardiomyopathy (HCM). HCM symptoms harm the quality of life, mental health, and physical well-being of patients. Researchers conducted this study to learn how HCM affects everyday life. To do this, patients with HCM completed surveys about their physical activity, symptoms, and mental health. They were also asked about what support and information they needed, and whether they told others about their HCM diagnosis.

What are the results?

There were 120 patients with HCM in the study. Many of them could no longer exercise or exercised less. Patients who had lifestyle changes had worse survey scores for physical activity, symptoms, and mental health than those who had no lifestyle changes. Physical activity was lower for patients with more severe heart failure symptoms. Almost all the patients noticed their HCM symptoms in the past year. Some of them thought these symptoms were caused by something else besides HCM. Most patients told others about their HCM. Patients wanted more information about HCM and its symptoms. Nearly all the patients in the study said their primary care physician was the main source of information about their condition.

What do the results of the study mean?

The results of this study will help doctors to better understand the needs of patients with HCM. Doctors should ask patients more questions about their physical activity, lifestyle changes, and symptoms. This will help doctors better understand the condition of their patients.

1. Introduction

Hypertrophic cardiomyopathy (HCM) is a chronic, progressive, clinically heterogeneous disease in which sarcomeric dysfunction causes left ventricular (LV) hypertrophy and fibrosis [1–3]. In 2021, the reported prevalence of HCM in Japan was 11.1 per 10,000 persons [4]. The initial presentation of HCM is impaired diastolic function, which can be detected using echocardiography [5,6]. As the disease progresses, patients experience LV wall thickening (hypertrophy), LV cavity shrinkage, diastolic dysfunction, and increased ventricular pressure, and they may also have increased pulmonary pressure and congestion. Patients with HCM are at an increased risk of progressive heart failure, stroke, sudden cardiac death, and both atrial and ventricular arrhythmias. Some patients with HCM may be asymptomatic, whereas others may experience symptoms that include shortness of breath, especially with physical exertion, fainting, chest pain, fatigue, dizziness, and palpitations from arrhythmias, including atrial flutter or atrial fibrillation [7,8]. HCM symptoms can substantially reduce patient quality of life (QOL) by negatively affecting mental and physical well-being, and impairing activities of daily living and work [7,9]; alongside reduced QOL, HCM is also associated with increases in societal costs [10].

We previously conducted a qualitative study of patients with HCM in Japan based on patient interviews [11] to further investigate the findings from previous studies. These studies have shown that patients with HCM are diverse, and there are individual differences in how they experience symptoms, which are important for treatment decision-making [12,13]. Second, treatment and lifestyle choices vary among patients [12]. Third, HCM is associated with an increased risk of mental disorders, and social concerns are common among these patients [14]. Finally, cultural factors and healthcare systems vary by country and may affect patients with HCM.

The findings from our qualitative study suggested that patients may be making lifestyle adjustments to avoid experiencing symptoms, or that they may be unaware of their symptoms and attribute physical changes to causes other than HCM [11]. However, it remains unclear whether these findings are generalizable to a larger patient population.

In the present quantitative study, patient-reported outcome (PRO) tools were administered to a larger patient cohort to verify the generalizability of the problem items identified in the qualitative study [11]. We used the International Physical Activity Questionnaire (IPAQ)—an index of physical activity—to quantify lifestyle adjustments related to the suggestion that patients adjust their lifestyle to help them avoid experiencing HCM symptoms. The IPAQ has been used previously to evaluate physical activity levels in patients with HCM [15]. Other PRO tools were also used, including the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Hypertrophic Cardiomyopathy Symptom Questionnaire (HCMSQ) as symptom indicators, and the Hospital Anxiety and Depression Scale (HADS) as an indicator of psychiatric illness. To date, no studies have examined the use of these PRO tools in real-world clinical practice in Japanese patients with HCM. Furthermore, in this study we developed and administered a questionnaire to assess patients’ interpretations of their lifestyle adjustments and to evaluate the observation that patients may attribute physical changes to causes other than HCM. The questionnaire was based on the insights gained through our previous qualitative research [11].

2. Patients & methods

2.1. Study design

This was a cross-sectional, non-interventional, observational study conducted between February 2025 and May 2025 in Japan. The study was conducted in two phases: a previously published qualitative phase [11] and the present quantitative phase. Patients were invited to participate in the study by their treating cardiologist. Cardiologists that were considered potential candidates for patient referral were identified from the M3 physician panel (M3, Inc., Tokyo, Japan) or belonged to healthcare facilities selected from a medical database analysis and internal market research data. Cardiologist selection was based on how many patients with HCM they were treating, the size of the healthcare facility they were affiliated with, their experience with clinical research related to patients with HCM, and the regions in which they were based. Cardiologists were selected from various regions in Japan to ensure generalizability and avoid bias. To ensure adequate representation from both the non-obstructive and obstructive HCM populations, participating physicians were asked to recruit patients from both categories. The study was not intended to estimate the national prevalence of each HCM type, but rather to allow exploratory comparisons between the non-obstructive and obstructive HCM patient populations. After providing written informed consent, the patients were given paper questionnaires and instructed to complete them at home. All information collected through the questionnaires was self-reported by the patients. Of note, the study was conducted prior to the market launch of cardiac myosin inhibitors (CMIs) in Japan, and patients who were participating in clinical trials were excluded from the study. Thus, it is expected that no patients who were taking CMIs were included in the study population.

2.2. Patients

Patients were eligible to participate if they were aged ≥18 years, had a confirmed diagnosis of non-obstructive or obstructive HCM, had been attending outpatient visits for HCM and were referred for this study by their HCM-treating physician, and had a New York Heart Association (NYHA) functional classification of 2 or 3 at enrollment. Obstructive HCM was defined as the presence of an LV outflow tract pressure gradient ≥30 mmHg at rest or on provocation, including exercise. Non-obstructive HCM was defined as the absence of an LV outflow tract pressure gradient ≥30 mmHg at rest and on provocation, including exercise. Patients were excluded if they had a previous or current diagnosis of dilated cardiomyopathy or secondary cardiomyopathy, including cardiac amyloidosis, Fabry disease, and mitochondrial myopathy, or had previously participated in (or were currently participating in) another clinical trial (not including observational studies). The study protocol was approved by the Takahashi Clinic Ethics Committee. The study was conducted in accordance with the Declaration of Helsinki and adhered to the Ethical Guidelines for Medical and Biological Research Involving Human Subjects and Japanese laws and regulations, and was registered at ClinicalTrials.gov under the identifier number NCT06181617. All study participants provided written informed consent.

2.3. Measures

Questionnaires were used to obtain quantitative data, including the validated HADS, KCCQ, HCMSQ, and IPAQ, as well as a questionnaire assessing participant demographic and clinical characteristics and a questionnaire assessing the burden of HCM, as identified in the qualitative phase [11].

2.3.1. HADS

Anxiety and depression were assessed using the HADS. This scale consists of seven items (rated 0, 1, 2, or 3) related to anxiety (subscale A) and seven other items related to depression (subscale D) [16]. The total subscale score ranges from 0 to 21, with higher scores reflecting worse health status.

2.3.2. KCCQ

Patient-reported health status was assessed using the KCCQ – Clinical Summary Score (CSS). The KCCQ [17] is a patient-reported questionnaire that measures the impact of cardiovascular disease/treatment on seven distinct domains using a 2-week recall: symptom stability, symptom frequency, symptom burden, physical limitations, QOL, social limitation, and self-efficacy. KCCQ-CSS is derived from the total symptom score and physical limitation score, and ranges from 0 to 100, with higher scores reflecting better health status.

2.3.3. HCMSQ

Shortness of breath (SoB) was assessed using HCMSQ-SoB domain scores. Overall, the HCMSQ [18] assesses the core symptoms of HCM, producing four domain scores, which include SoB, as well as tiredness, cardiovascular symptoms, and syncope. Participants were asked to complete the HCMSQ over a 7-day recall period.

2.3.4. IPAQ

Physical activity was assessed using the short version of the IPAQ [19], with the IPAQ [20] being considered the most representative physical activity assessment questionnaire. The short version of the IPAQ consists of four items: moderate-intensity active time, vigorous-intensity active time, walking time, and sitting time. Metabolic equivalent of task (MET)-minutes/week was calculated according to the IPAQ guideline [21].

2.3.5. Demographic and clinical characteristics questionnaire

The demographic and clinical characteristics questionnaire included patient-reported information related to age, employment status, co-residing family members, mental disorders currently under medical treatment, family history of HCM, history of non-drug therapy, self-reported NYHA functional classification, need for support/caregivers due to HCM, body mass index (based on height and weight), and period from first HCM diagnosis.

2.3.6. Burden of HCM questionnaire

The findings of the qualitative phase suggested that patients with HCM adjust their lifestyles to avoid experiencing symptoms [11]. To verify this observation, we developed a burden of HCM questionnaire based on the items identified in the qualitative phase. Following the initial draft of the questionnaire, the contents were reviewed by two HCM specialists. To confirm the ease of understanding, consistency of interpretation, and answerability of each question, the questionnaire was then tested on six patients with HCM. Through these processes, the validity of the questions was evaluated, and any necessary changes were made prior to creating the final version used in this study. The questionnaire assessed changes in daily activity due to HCM, changes in free time due to HCM, symptoms of HCM that are known as symptoms due to HCM by and have been experienced by the patient, patients’ thoughts about the causes of the symptoms they have experienced, patients’ communication about HCM with the people around them, patients’ experiences and thoughts about surgical intervention, and the support and information needed by patients. Patients who responded “slightly changed” or “changed” when asked about changes in free/leisure time due to HCM were considered to have experienced changes, whereas those who responded “no change” or “not much change” were considered to have not experienced changes.

2.4. Objectives

The primary objective was to describe the clinical, physical, and humanistic burden of HCM using the HADS, KCCQ, HCMSQ, and IPAQ PRO tools, as well as the questionnaire developed based on the qualitative phase.

The secondary objectives were to investigate the relationship between each health-related (HR)-QOL score and patient demographic/clinical characteristics, as well as the relationships between each HR-QOL score. The exploratory objectives were to assess the HR-QOL score by HCM category (obstructive or non-obstructive) and by the presence or absence of lifestyle changes.

2.5. Statistical analysis

This study used descriptive statistics. As such, no statistical sample size calculation was conducted. The sample size was set at 100 patients (50 with obstructive HCM and 50 with non-obstructive HCM) based on feasibility and previous studies that evaluated the relationship between PROs associated with anxiety or KCCQ and disease perception [22–25].

Descriptive statistics were used to summarize the questionnaire scores for the total population (primary objective) and by HCM type (obstructive vs. non-obstructive) and lifestyle changes (presence vs. absence) (exploratory objectives). Categorical variables were summarized as n (%) and continuous variables as the mean ± standard deviation or median (interquartile range). Spearman’s rank correlation coefficient or Wilcoxon’s rank-sum test was used to identify associations of HADS, KCCQ, HCMSQ, and IPAQ scores with demographic/clinical characteristics and other HR-QOL scores (secondary objectives). Missing data were not imputed. Given that this was an exploratory study, the analysis did not include multiple testing correction. As such, the results should be interpreted as hypothesis-generating findings. Statistical analyses were performed using SAS, version 9.4 (SAS Institute Inc., Cary, NC, USA).

3. Results

3.1. Patient characteristics

In total, 130 patients were enrolled; 10 were excluded (did not meet the inclusion criteria, n = 9; met the exclusion criteria, n = 1), and 120 were included in the analysis (Figure 1). Of these, 60 patients (50.0%) had obstructive HCM and 60 (50.0%) had non-obstructive HCM. The mean age was 59.1 ± 16.3 years (Table 1, Supplemental Figure S1); 55.5% (66/120) were male; 90.8% (109/120) had received medication for HCM (Table 1); and 6.7% (8/120), 14.2% (17/120), 21.7% (26/120), and 4.2% (5/120) had undergone surgical myectomy, percutaneous transluminal septal myocardial ablation, implantable cardioverter-defibrillator implantation, and pacemaker implantation, respectively (Supplemental Table S1). Most patients (65.8%; 79/120) self-reported their NYHA functional classification as “slight limitation of physical activity, comfortable at rest, ordinary physical activity results in fatigue, palpitation, shortness of breath or chest pain” (Table 1). Of the 111 patients for whom data were available, 7.2% (8/111) and 5.4% (6/111) had previously or were currently receiving medical treatment for psychiatric disorders, respectively (Table 1). Of the 120 patients surveyed, 6.7% (8/120) required support and nursing care in their daily lives because of HCM (Table 1). Most questions had a response rate of >90%. Owing to patient difficulty in understanding the question, the response rate for Q17-2 about changes in the past year pointed out by others was low (approximately 30%). There were no substantial differences in the background information between the respondents and non-respondents to Q17-2 (Supplemental Table S2).

Figure 1.

Patient disposition.

Abbreviations: HCM, hypertrophic cardiomyopathy.

Table 1.

Patient background demographic and clinical characteristics.

	Total population (n = 120)
Demographic and clinical characteristics
Age, years, mean ± SD	59.1 ± 16.3
Sex, male	66 (55.5)
Body mass index, kg/m2, mean ± SD	24.2 ± 3.9
Age at diagnosis, years, mean ± SD	48.0 ± 17.8
Currently receiving pharmaceutical treatment for HCM
Yes	109 (90.8)
No	9 (7.5)
Unknown	2 (1.7)
Self-reported NYHA functional class
No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, or shortness of breath (NYHA class 1).	10 (8.3)
Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, shortness of breath or chest pain (NYHA class 2).	79 (65.8)
Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, shortness of breath or chest pain (NYHA class 3).	31 (25.8)
Symptoms of heart failure at rest. Any physical activity causes further discomfort (NYHA class 4).	0 (0.0)
Patient-reported comorbidities and symptoms
Heart failure	29 (24.2)
Atrial fibrillation	23 (19.2)
History of myocardial infarction	3 (2.5)
History of cerebral infarction	7 (5.8)
Diabetes	12 (10.0)
Hypertension	35 (29.2)
Ventricular arrhythmia	19 (15.8)
Malignant tumor	5 (4.2)
Angina pectoris	4 (3.3)
Syncope	10 (8.3)
None	30 (25.0)
Unknown	12 (10.0)
Psychiatric disorders currently receiving medical treatmenta
Currently undergoing medical treatment or taking medication	6 (5.4)
Previously received medical treatment such as outpatient visits or medication, but currently not receiving such treatment	8 (7.2)
I have never received medical treatment or medication for a psychiatric illness	97 (87.4)
Need for support and nursing care
Yes	8 (6.7)
No	111 (92.5)
Unknown	1 (0.8)

Abbreviations: HCM, hypertrophic cardiomyopathy; NYHA, New York Heart Association; SD, standard deviation.

Data are n (%) unless otherwise indicated.

^aData were missing for nine patients.

3.2. Impact of HCM on activities and HR-QOL score

3.2.1. Changes in work, housework, and other activities due to HCM

Over half of the respondents reported that their work and housework activities remained unchanged, although a large proportion reported that they could no longer exercise or had substantially reduced the amount of exercise they did at an intensity greater than walking (Figure 2(a)). Approximately 40% of the participants reported that their leisure/free time activities had changed somewhat or significantly because of HCM (Figure 2(b)). Examples of these changes were “I go shopping and to the mall less frequently now. I find it difficult to walk long distances when going out with my family, so I use a wheelchair. I spend more time lying down at home. I travel and drive less, which I enjoy.” and “I can no longer do strenuous activities like sports and running” (Supplemental Table S3, S4). The comparison of changes in how leisure/free time was spent between patients who responded that they “can no longer” exercise at an intensity greater than walking and patients who responded that they “never did it in the first place” showed that a higher proportion of patients who responded that they could no longer exercise reported changes in their leisure/free time (Supplemental Table S5).

Figure 2.

Changes in daily life (a) and leisure time (b) due to HCM.

Abbreviations: HCM, hypertrophic cardiomyopathy.

3.2.2. IPAQ and HR-QOL score

Median KCCQ-CSS, HADS-Depression, and HCMSQ SoB domain scores were significantly worse for patients who experienced changes in free/leisure time than for those who did not (KCCQ-CSS, 81.3 vs. 92.0, p < 0.001; HADS-Depression, 5.0 vs. 2.0, p = 0.001; HCMSQ SoB, 5.0 vs. 3.0, p < 0.001; Table 2, Supplemental Figure S2). Although the difference in the median IPAQ score between patients who experienced changes in free/leisure time and those who did not was not statistically significant, the score was numerically lower among those with changes in free/leisure time (495.0 vs. 990.0, respectively, p = 0.159).

Table 2.

Summary questionnaire scores (median/mean) for the total population and stratified by whether patients experienced lifestyle changes.

	IPAQ	KCCQ-CSS	HADS-Anxiety	HADS-Depression	HCMSQ SoB
All	n = 117	n = 118	n = 120	n = 120	n = 119
Median (IQR)	891.0 (371.3–1980.0)	87.8 (76.1–96.9)	4.0 (2.0–6.0)	3.0 (1.0–6.0)	4.0 (1.0–5.0)
Mean ± SD	1699.9 ± 2144.9	84.5 ± 14.2	4.2 ± 3.1	4.3 ± 3.7	3.4 ± 2.8
Experienced changes in free/leisure time due to HCMa
Median (IQR)	495.0 (363.0–1803.5)b	81.3 (65.6–90.7)c	4.0 (2.0–6.0)	5.0 (3.0–8.0)	5.0 (2.0–6.0)c
Mean ± SD	1272.1 ± 1633.4b	77.6 ± 16.1c	4.7 ± 3.6	5.6 ± 4.1	4.4 ± 2.9c
Experienced no changes in free/leisure time due to HCMd
Median (IQR)	990.0 (369.4–2295.0)c	92.0 (81.4–97.9)c	4.0 (1.0–6.0)	2.0 (1.0–6.0)	3.0 (0.0–4.5)
Mean ± SD	1922.8 ± 2374.1c	89.6 ± 10.4c	3.8 ± 2.8	3.4 ± 3.3	2.7 ± 2.5
Mann–Whitney U test, p-value	0.159	<0.001	0.272	0.001	<0.001

Abbreviations: HADS, Hospital Anxiety and Depression Scale; HCM, hypertrophic cardiomyopathy; HCMSQ SoB, Hypertrophic Cardiomyopathy Symptom Questionnaire Shortness of Breath domain score; IPAQ, International Physical Activity Questionnaire; IQR, interquartile range; KCCQ-CSS, Kansas City Cardiomyopathy Questionnaire – Clinical Summary Score; SD, standard deviation.

^aMedian (IQR) age: 62.0 (51.0–75.0) years; mean ± SD age: 61.1 ± 16.2 years.

^bData were missing for two patients.

^cData were missing for one patient.

^dMedian (IQR) age: 60.0 (48.0–69.5) years; mean ± SD age: 57.7 ± 16.6 years.

As a reference, the Japanese Ministry of Health, Labour and Welfare recommends 1,380 MET-minutes/week for adults and 900 MET-minutes/week for older individuals [26]. Among adults (aged < 65 years) and older people (aged ≥ 65 years) with HCM, only 33.8% (24/71) and 50.0% (23/46), respectively, achieved recommended MET-minute scores (Table 3).

Table 3.

IPAQ score and percentage of patients with a higher score than recommended by the Ministry of Health, Labour and Welfare.

	Total population (n = 120)a	Patients aged <65 years (n = 71)	Patients aged ≥65 years (n = 49)a
IPAQ, MET-minutes/week
Median (IQR)	891.0 (371.3–1980.0)	891.0 (417.0–1824.0)	891.0 (272.3–3460.5)
Mean ± SD	1699.9 ± 2144.9	1484.0 ± 1903.0	2033.1 ± 2457.5
Patients whose IPAQ was higher than recommendedb, % (number of patients meeting the recommendation/number of patients)	40.2 (47/117)	33.8 (24/71)	50.0 (23/46)

Abbreviations: IPAQ, International Physical Activity Questionnaire; IQR, interquartile range; MET-minutes/week, metabolic equivalent of task minutes per week; SD, standard deviation.

^aData were missing for three patients.

^bRecommendation of Japanese Ministry of Health, Labour and Welfare: adults, 1,380 MET-minutes/week; elderly, 900 MET-minutes/week [25].

When evaluating the relationship between PRO questionnaire scores and self-reported NYHA functional class, which was based on a comparison of median PRO values for patients in each NYHA functional class, a higher NYHA functional class was associated with decreased physical activity (Supplemental Table S6).

When comparing the scores between patients with obstructive HCM and those with non-obstructive HCM, the only significant difference between the subgroups was observed for the KCCQ-CCS score, with a significantly lower median score in patients with obstructive HCM (85.8 vs. 91.3, p = 0.031). For the other scores, patients with obstructive HCM had a numerically lower median IPAQ score (~310 points), a numerically higher (0.6 points) mean HADS-Depression score, a similar HADS-Anxiety score, and a numerically higher (~1 point) HCMSQ SoB score than patients with non-obstructive HCM (Supplemental Table S7). No significant differences were observed in any of the scores between patients with and without a family history of HCM (Supplemental Table S8).

Correlations of the HADS scores with HCMSQ SoB, KCCQ-CSS, and IPAQ scores are shown in Supplemental Table S9 and Supplemental Figure S3. The HADS scores had moderate or higher correlations with KCCQ-CSS and HCMSQ SoB scores.

3.3. HCM symptoms, interpretation of symptom causes, and disclosure to others

Overall, 83.9% (99/118) of the patients reported noticing symptoms of HCM within the last year, while 21.2% (25/118) reported that they were made aware of their HCM symptoms by others (Supplemental Table S10). Of the 25 patients whose symptoms were pointed out by others, 24 (96.0%) were also aware of their symptoms.

In the present quantitative phase of the study, the percentages of patients who attributed fatigue and dizziness to factors other than HCM were relatively high at 37.3% (41/110) and 39.5% (34/86), respectively (Supplemental Table S11). 23.3% (14/60) of the patients attributed chest pain, a symptom with a relatively high specificity for HCM, to factors other than HCM (Supplemental Table S11).

Most patients (89.0%, 105/118) told those around them that they had HCM. The main reasons were that “It is natural to tell people you have an illness” and “It is for emergency preparedness” (Supplemental Table S12). The percentage of patients who did not tell those around them about their HCM was 11.0% (13/118). The main reasons were that “It is not necessary” and that “There are no noticeable symptoms, and no support would be given even if I spoke up.”

3.4. Support and information needed by patients

Patients reported that they needed information about HCM and about systems related to HCM, such as the intractable disease subsidy system (Table 4). In total, 99.2% (119/120) of the patients responded that their primary care physician was a source of information about HCM.

Table 4.

Support and information required by patients with HCM.

Support needed for HCM, n (%)	1st need	2nd need
Providing information about HCM (information about hypertrophic cardiomyopathy)	44 (36.7)	21 (17.5)
Providing information about HCM (information other than about the disease itself, such as assistance programs for intractable diseases)	10 (8.3)	28 (23.3)
Opportunities for communication and community among patients	0 (0.0)	3 (2.5)
Dedicated consultation desk for counseling, mental health, etc.	2 (1.7)	5 (4.2)
Systems for consulting with medical professionals, such as physicians and nurses	14 (11.7)	17 (14.2)
Providing information on specialized facilities and specialists for HCM	9 (7.5)	14 (11.7)
Financial support such as medical expenses subsidies for incurable diseases	28 (23.3)	9 (7.5)
Others	2 (1.7)	0 (0.0)
No support needed	5 (4.2)	0 (0.0)
No answer	6 (5.0)	23 (19.2)
Sources of information about HCM, n (%)	Total population (n = 120)
Primary care physician	119 (99.2)
Other physician (second opinion)	8 (6.7)
Other healthcare professionals (nurses, pharmacists, etc.)	5 (4.2)
Leaflets distributed at the hospital	10 (8.3)
Family	8 (6.7)
Friends, acquaintances	6 (5.0)
Patient associations	0 (0.0)
TV, radio	3 (2.5)
Newspapers, magazines	8 (6.7)
Books	15 (12.5)
Search engine websites (Google, Yahoo! JAPAN, etc.)	59 (49.2)
Internet: Hospital homepage	17 (14.2)
Internet: Pharmaceutical company homepage	10 (8.3)
Internet: Personal blogs, social media	12 (10.0)
Internet: Other	15 (12.5)
Other sources of information	1 (0.8)
Not particularly referring to any source of information	4 (3.3)

Abbreviations: HCM, hypertrophic cardiomyopathy.

4. Discussion

This study used a custom-designed questionnaire, developed based on the realities of the burden experienced by Japanese patients with HCM as revealed in the qualitative phase [11] of the study, to examine perspectives not covered by existing survey instruments. Furthermore, the study provides important insights regarding physician-patient communication, including patients’ misconceptions attributing physical HCM symptoms to non-HCM causes and the specific informational needs of patients. The findings of the qualitative phase of this observational study suggested that patients with HCM may adjust their lifestyle to avoid experiencing symptoms [11], which was verified in the present quantitative phase. While this finding has been reported based on data outside of Japan [27], this is the first study to demonstrate that similar trends exist within the distinct social systems and cultural context of Japan. The scores from the PRO questionnaires also suggested that the patients live a lifestyle that avoids symptoms. For example, although patients reported experiencing shortness of breath (HCMSQ SoB scores), the IPAQ scores suggested that they adjusted their lifestyle (i.e., adjusting their physical activity) simultaneously. Such adjustments likely contributed to the relatively high KCCQ-CSS scores. Another possible contributor is the slow progression of HCM symptoms. The study findings suggest that insensitivity to HCM symptoms may be determined by a patient’s activity level prior to developing HCM symptoms. Patients with HCM experienced a decrease in exercise at an intensity greater than walking, and patients who originally engaged in such activities were more likely to experience changes in how they spent their leisure/free time. Therefore, inquiring about a patient’s previous activity level and lifestyle changes may be an effective tool for understanding their condition.

Findings from the qualitative phase suggested that patients may be unaware of their symptoms [11]. However, the present quantitative phase found that 83.9% of patients were aware of their symptoms. Only 21.2% of the patients had been made aware of their symptoms by others, and nearly all patients who had their symptoms pointed out to them by others also reported being aware of their symptoms. This finding highlights the importance of listening to the subjective symptoms of patients to comprehensively understand their condition. Discrepancies between the qualitative and quantitative findings indicate that patient responses may have been influenced by the phrasing of the questions. While the qualitative phase used open-ended questions, the quantitative phase asked about specific symptoms. Thus, asking direct questions about individual symptoms may be more effective for capturing a comprehensive picture of each patient’s condition.

In the present study, most patients (89.0%) informed the people around them about their HCM diagnosis, in contrast with the qualitative phase in which the patients tended to be hesitant in informing those around them of their HCM diagnosis [11]. However, in the quantitative phase, 11.0% of patients did not inform those around them because they did not feel it necessary, or because they did not have symptoms and expected that they would not receive support even if they mentioned their condition to others.

The findings of the quantitative phase align with the previous qualitative phase, which suggested that patients may be aware of physical changes due to HCM, but that they sometimes attributed these changes to factors other than HCM, such as age, obesity, or other factors [11]. In the present quantitative phase, patients also often attributed their physical changes to factors other than HCM. Although the number of patients was small, chest pain, which is a relatively specific symptom of HCM, was often reported as a symptom that patients attributed to factors other than HCM. These findings suggest the need for detailed symptom identification, and physicians should ask patients whether they are experiencing a variety of symptoms.

The previous qualitative phase revealed that patients wanted concise information about the disease provided by experts and hospital staff, and they wanted to learn about the experiences of other patients [11]. The present study found that patients mainly wanted information about the disease itself and designated intractable diseases. Nearly all patients (99.2%) reported that their primary care physician was a source of information about HCM, but media that can widely educate patients about HCM is needed. It is also important to raise awareness of Japan’s unique designated intractable disease system, which is a public assistance program aimed at reducing the financial burden on patients suffering from diseases classified as “designated intractable diseases.”

This is the first study to report physical activity levels and real-world data evaluating KCCQ, HCMSQ, and HADS scores among Japanese patients with HCM. Patients with HCM appeared to have low physical activity levels. For many patients, physical activity levels were lower than the Ministry of Health, Labour and Welfare’s recommended standards for both adults and elderly people [26]. Median IPAQ scores were lower than those reported for elderly Japanese adults in the Fujiwara-kyo study [28] and tended to be lower than those reported in a nationwide survey in terms of patients who met the aforementioned physical activity level standards (present study vs. nationwide survey: adults, 33.8% vs. 45.6%; elderly, 50.0% vs. 61.7%) [29]. However, the nationwide survey used an accelerometer, indicating that there may have been methodological differences.

Correlations between subjective questionnaire scores and objective accelerometer values vary across reports (e.g., the correlation between IPAQ score and accelerometer values in patients with diabetes was high [r = 0.69], but the IPAQ may overestimate physical activity compared with accelerometer values) [15,30]. Appropriate exercise guidance by physicians tailored to each patient’s condition is essential. This study confirmed that patients with HCM have low physical activity, which is thought to be because both the patients and their physicians impose restrictions on physical activity [31,32]. However, too little physical activity adversely affects health [15,27], while exercise interventions can lead to improvements in cardiorespiratory fitness, left ventricular wall thickness, and body mass index among patients with HCM [33]. QOL may also be affected by activity levels, with a recent study that used accelerometry to investigate activity levels in patients with HCM showing that even modest increases in daily step counts were associated with better QOL [27], and a meta-analysis demonstrating improved QOL physical factor following structured exercise programs [33]. Considering that 99.2% of the patients obtained information from their primary care physician, it is important that physicians understand the importance of physical activity and provide appropriate exercise guidance tailored to each patient’s situation. In addition, further research is needed to clarify appropriate exercise criteria for patients with HCM.

The KCCQ data showed that patients with HCM believed they were in good health owing to lifestyle adjustments. The mean KCCQ-CSS score was 84.5, which is within the normal range (good to excellent, 75–100) and varies according to self-reported NYHA functional class [34]. The high KCCQ score was possibly due to patients adjusting their lifestyle to avoid HCM symptoms. The KCCQ-CSS values reported in the present study were somewhat higher than those reported in HCM clinical trials [35,36]. They also tended to be higher than those in a validation study of the KCCQ in Japanese patients with chronic heart failure [34]. However, the relatively high KCCQ-CSS scores in this study may reflect differences between clinical trials and real-world clinical practice. The reproducibility of KCCQ data in real-world studies of patients with HCM must be confirmed.

The symptoms of patients in this study were mild to moderate according to their HCMSQ SoB scores. The values tended to be lower than those reported in the EXPLORER-HCM clinical trial, but they were comparable to values reported for patients who had a mild severity level on the Patient Global Impression of Severity scale [18,35]. When stratified by self-reported NYHA scores (mean HCMSQ SoB: NYHA 2, 3.0; NYHA 3, 5.6), HCMSQ SoB scores were equivalent to those reported in the EXPLORER-HCM study [35]. Furthermore, the HCMSQ SoB score was approximately 1 point higher in patients with obstructive HCM than in those with non-obstructive HCM. The clinically significant difference in HCMSQ SoB was reported to be ≥2.5 points in an anchor-based analysis, suggesting there may be a clinically significant difference between NYHA subgroups [37]. Compared with the KCCQ-CSS scores, which were within the normal range, HCMSQ SoB scores may be more useful for assessing patient status in clinical practice. While the KCCQ includes a wide range of questions, such as the ease of everyday activities, the HCMSQ SoB focuses specifically on shortness of breath, making it easier to detect abnormalities in patients.

The HADS results suggest that mental health concerns may need to be considered in more severely affected patients. HADS scores were normal based on the cutoff value of 8, as proposed in a previous study [38]. In this study, the percentage of patients with a history of psychiatric treatment was low (7.2%), as was the percentage of patients currently receiving psychiatric treatment (5.4%), reflecting the expectation that the overall scores would be low. In comparison, a previous study reported that 21% of patients with HCM had depression and 39% had anxiety disorders [38]. Increased severity, as indicated by the self-reported NYHA scores, was associated with increased HADS scores. This result suggests that patients’ mental burden may be more influenced by HR-QOL and symptoms than by physical activity. When considering HADS-Depression scores between patients with obstructive versus non-obstructive HCM, the 0.6-point score difference between the subgroups did not reach the minimal clinically important difference of 1.7 points, suggesting there may be no difference in depression level between the subgroups [39]. Although no correlation was found between the HADS and IPAQ scores in this study, correlations have been reported in previous studies in the general population [40,41]. A previous study also reported correlations between HADS and KCCQ scores [42].

This study had several strengths. It is the first real-world quantitative study in Japan targeting a wide range of patients with HCM. The survey was conducted using a simple questionnaire rather than more complex devices, such as smartwatches, making it easy to apply in clinical practice. All participants had received a definitive diagnosis of HCM from a specialist, making the data highly reliable. By verifying the generality and detailed descriptions of the newly identified items from the qualitative survey across a wide range of patients, we were able to identify new items and insights for understanding the symptoms of patients with HCM. Additionally, the findings from the study provide useful insights that can be considered in real-world care for patients with HCM. First, we found that patients commonly adjust their lifestyles to avoid experiencing symptoms or misattribute the causes of their physical symptoms. This highlights the need for physicians to conduct thorough patient interviews and maintain effective communication to ensure that symptom worsening is not overlooked during clinical care. Second, the present study found that exercise restrictions often lead to greater-than-necessary reductions in physical activity levels in patients with HCM. This underscores the importance of moving away from blanket exercise restrictions and instead providing appropriate, individualized exercise guidance and establishing clear standards. Ultimately, these insights can serve as a stepping stone toward more patient-centric treatment in HCM.

The findings of this study also need to be considered in light of its limitations. Detailed clinical information based on physician diagnosis was not obtained, except for the HCM subtype and whether the patients were symptomatic. Sampling patients with severe HCM or severe psychiatric symptoms may have been difficult, so the study findings may not be generalizable to the entire population of patients with HCM. In addition, this was a cross-sectional study and did not contain data in a temporal sequence. Considering that HCM onset is difficult to detect, comparisons of questionnaire scores before and after HCM onset were not possible. Moreover, NYHA class was self-reported by the patients, which may correlate with PROs due to common method bias. It was also not clear whether the lifestyle adjustments reported in this study were made based on a patient’s symptoms or instructions from their physician. Furthermore, as the study was conducted by specialists, there is a possibility of selection bias. Patients with psychiatric disorders who may have difficulty responding to questionnaires may have been omitted by physicians when distributing the study materials. Although the study employed a non-probability sample, a comparison of available baseline characteristics between the present study and the J-HCM and REVEAL-HCM Japanese registry studies shows that while the male-to-female ratio was comparable to that of domestic registries, the study population tended to be younger [43,44]. Given that the study was exploratory and descriptive in nature and that there was no formal sample size calculation, some non-significant results may have been influenced by a lack of statistical power. Future studies with larger populations are needed to validate the study findings. Additionally, owing to the exploratory nature of the study, the analysis did not include multiple testing correction; as such, the results should be considered hypothesis-generating. Multivariate analysis was not performed because, in addition to the lack of detailed clinical data, certain variables such as NYHA functional class may act as mediators in the association between lifestyle changes and HR-QOL. Accordingly, adjusting for them could lead to over-adjustment. It should also be considered that although 90.8% of patients were receiving pharmacological treatment, detailed information regarding that treatment was not collected. We cannot rule out the possibility that pharmacological treatment influenced patient QOL and introduced bias into the study results. However, based on the timing of the study and eligibility criteria, it is considered that patients taking CMIs were not included. Additionally, while the findings of the previous qualitative phase suggested that patients may not be able to talk to their physician about their concerns during their appointment [11], this was not further investigated in the quantitative phase. The burden of HCM questionnaire was developed based on the findings of the qualitative phase of the study and formal psychometric verification was not conducted. We note that the response rate for Q17-2 (a question regarding changes noted by others over the past year) was quite low at approximately 30%, which may indicate that the question was difficult to understand. Given the low response rate, results for this question require cautious interpretation. Finally, it is possible that patients’ understanding of their experience varies.

5. Conclusions

Aligned with the previous qualitative phase, the quantitative phase of this study suggested that patients with HCM may adjust their lifestyle to avoid experiencing HCM symptoms. Furthermore, physical symptoms of HCM that were often misunderstood by patients as being caused by factors other than HCM were identified. Most patients with HCM chose to tell others about their disease. The quantitative phase also revealed that patients want further information about both the disease itself and about its designated intractable disease status. Most patients identified their primary care physician as a source of HCM-related information. In the future, prospective and interventional studies are needed to evaluate how symptom‑driven reductions in physical activity among patients with HCM relate to objectively measured activity, longitudinal PRO changes (KCCQ/HCMSQ), exercise tolerance or frailty, and long‑term outcomes, such as heart failure events and hospitalizations.

Funding Statement

This manuscript was funded by Bristol Myers Squibb. Yuika Ikeda and Makio Torigoe, who are employees of Bristol Myers Squibb, were involved in the study design, decision to publish, and preparation of the manuscript.

Article highlights

• This manuscript reports the quantitative phase of a study investigating factors that affect health-related quality of life among patients with hypertrophic cardiomyopathy (HCM) and aimed to verify problem items identified in the qualitative phase.

• This is the first study to report physical activity levels and real-world data evaluating Kansas City Cardiomyopathy Questionnaire, Hypertrophic Cardiomyopathy Symptom Questionnaire, and Hospital Anxiety and Depression Scale scores in Japanese patients with HCM.

• The quantitative analysis suggested that patients with HCM may adjust their lifestyle to avoid experiencing HCM symptoms.

• Many patients thought that certain HCM symptoms they were experiencing had causes other than HCM; these symptoms were identified.

• Patients with HCM wanted more information about the disease and its designated intractable disease status.

• Primary care physicians were the primary source of HCM-related information for most patients.

Disclosure statement

This study was funded by Bristol Myers Squibb. Kanako Shimoura, Shintaro Suo, and Ryohei Takeda are employees of Mebix, Inc, which was outsourced by Bristol Myers Squibb to perform this study. Hiroaki Kitaoka has received fees from AstraZeneca, Alnylam Japan, Alexion Pharmaceuticals, Bayer, Pfizer, and Bristol Myers Squibb. Toru Kubo has received fees from Pfizer, Alnylam Japan, Alexion Pharmaceuticals, Sumitomo Pharma, Takeda, AstraZeneca, and Bristol Myers Squibb. Yuichiro Maekawa has received donations for scholarship funds from Abbott Medical Japan and Biotronik Japan, and lecture fees from Bristol Myers Squibb. Yuika Ikeda and Makio Torigoe are employees of Bristol Myers Squibb and own stocks in Bristol Myers Squibb.

The authors report generative AI was not used in their research or preparation of this manuscript.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Ethical declaration

The protocol was approved by the Takahashi Clinic Ethics Committee (approval no. LNW00199), and the study was conducted in accordance with the Declaration of Helsinki and adhered to the Ethical Guidelines for Medical and Biological Research Involving Human Subjects and all applicable Japanese laws and regulations. All study participants provided informed consent. This study was registered at ClinicalTrials.gov under the identifier number NCT06181617.

Data sharing statement

The data that support the findings of this study are available on reasonable request from the corresponding author.

This study was conducted in Japan.

Writing assistance

Emily Woodhouse, PhD, and Sarah Bubeck, PhD, of Edanz (www.edanz.com) provided medical writing support, which was funded by Bristol Myers Squibb in accordance with Good Publication Practice guidelines (http://www.ismpp.org/gpp-2022).

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14796678.2026.2745404