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06/01/2026 | Press release | Distributed by Public on 06/02/2026 15:15
Real-world Burden of Hypertrophic Cardiomyopathy on Healthcare Use and Health-related Quality of Life in Italy, Spain, and the United States
Background and aims
Hypertrophic cardiomyopathy (HCM) is a chronic, progressive, genetic heart disease characterized by hypercontractility and hypertrophy. As treatment options evolve, characterizing the existing healthcare needs and health-related quality of life (HRQoL) for patients with HCM is important.
Methods
Data were derived from the Adelphi Real World HCM Disease Specific Programme, a cross-sectional survey in Italy, Spain, and the United States. Physicians reported demographic and clinical characteristics; patients completed the Kansas City Cardiomyopathy Questionnaire (KCCQ-23), EQ-5D-5L and EQ-VAS, and the Work Productivity and Activity Impairment (WPAI) questionnaire. Outcomes were statistically compared by New York Heart Association (NYHA) class or KCCQ clinical summary score (KCCQ-CSS) to assess impact of disease severity.
Results
Patient mean age was 56.5 ± 14.8 years; 60.7% were male, and 78.3% had NYHA class II disease. Patients most commonly received beta blockers (88.4%) and diuretics (31.8%). HCM-related hospitalizations were reported for 25.8% of patients, increasing with higher NYHA or lower KCCQ-CSS. Mean EQ-5D-5L was 0.85, while EQ-VAS was 75.0, both decreasing with higher NYHA class or lower KCCQ-CSS. Overall work impairment and activity impairment (WPAI) were 16.1% and 26.6%, respectively, increasing with higher NYHA class or lower KCCQ-CSS.
Conclusion
Our data show a significant remaining symptom burden and healthcare resource utilization (HCRU), as well as impact on HRQoL, work productivity, and daily activities, despite treatment intervention across a commonly applied measure of disease severity in HCM. These findings underscore the need for new treatments that can reduce HCRU and improve HRQoL of patients with HCM.
GRAPHICAL ABSTRACT
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Multi-panel infographic showing survey data on health-related quality of life and hospitalization trends for patients with HCM.
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Keywords:
Hypertrophic cardiomyopathyhealthcare resource utilizationquality of lifework productivitysymptom burdeneconomic burden
JEL CLASSIFICATION CODES:
Z00I00I10
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Introduction
Hypertrophic cardiomyopathy (HCM) is a chronic, progressive heart disease initially characterized by cardiac muscle hypercontractility and left ventricle hypertrophy, but hypocontractility may occur in advanced casesCitation1. It is predominantly of genetic origin, but sporadic cases may also occurCitation2. While the overall prevalence of HCM in the United States (US) has been estimated around 20/10,000Citation3, recent estimates suggest a prevalence of 30.6/10,000 (approximately 1 in 327 individuals)Citation4. Corresponding estimates range from 3.3 to 11.7/10,000Citation4-6 for obstructive HCM (oHCM) and 1.3 to 18.8/10,000Citation4-6 for non-obstructive HCM (nHCM) in the US and Europe.
Classification of HCM is established based on level of hypertrophy into oHCM, when the left ventricular outflow tract is obstructed, or nHCM disease, when it is notCitation1. Although some patients may remain asymptomatic throughout life, HCM is frequently associated with symptoms such as dyspnea, light-headedness, palpitations, limited exercise capacity, and fatigueCitation1. Severity of HCM is often assessed using the New York Heart Association (NYHA) functional classification; higher NYHA class is associated with worse clinical outcomesCitation7 and increased all-cause mortalityCitation8 in patients with oHCM, but data on nHCM remain limitedCitation9,Citation10.
Additionally, disease severity and progression may be assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ-23), with scores being correlated with clinical outcomes and mortality rates in other cardiovascular conditionsCitation11,Citation12. The clinical summary score component of the KCCQ (KCCQ-CSS) focuses on the most clinically relevant manifestations of heart failure and includes the total symptom burden and physical limitationsCitation13-15. Lower KCCQ-CSS is strongly associated with increased risk of all-cause mortality and heart failure hospitalizations in real-world heart failure populationsCitation16,Citation17. NYHA class and KCCQ-CSS have been used as clinical endpoints in recent phase 3 clinical trials in HCMCitation18-21.
Guideline-recommended pharmacotherapies for HCM include treatments such as beta blockers, calcium channel blockers, and disopyramideCitation22. Those treatments intend to control symptoms but do not change the underlying disease courseCitation23. Despite receiving these pharmacotherapies, some patients may not achieve adequate symptomatic relief and may require surgical treatment options such as septal myectomy or alcohol septal ablationCitation24,Citation25. After undergoing invasive treatment, a subset of patients experienced disease progression, which was associated with worse clinical outcomes including atrial fibrillation, heart failure, and HCM-related mortalityCitation26. Recently, treatments targeting the hypercontractility associated with HCM pathophysiology are reaching the clinic, with the cardiac myosin inhibitor mavacamten gaining regulatory approval for oHCM in 2022 (US FDA) and 2023 (Europe EMA)Citation27, and the cardiac myosin inhibitor aficamten gaining regulatory approval for oHCM in 2025 (US FDA)Citation28.
Patients with oHCM have high healthcare resource utilization (HCRU), with robust data available from the US showing high hospitalization rates, frequent outpatient visits, and high associated healthcare costsCitation29-31. However, few data are available for European patients with oHCMCitation32-34, and recent data for nHCM are largely lacking. The symptom and HCRU burden associated with HCM may also impact patient health-related quality of life (HRQoL), as well as work and daily activities. Impaired HRQoL has been well characterized in patients with oHCM in clinical trial settingsCitation35-37. However, little real-world data exist, with one study showing that patients with more severe HCM by NYHA class have greater impairment of their HRQoLCitation38. Therefore, a continued need exists for a comprehensive assessment of HRQoL and impact on work and activities in patients with HCM to further optimize their treatment.
The objective of this study is two-fold: to characterize HCRU, HRQoL, and work and activity impairment in patients with HCM and to assess the impact of disease progression, as measured by NYHA class and KCCQ-CSS, on those outcomes.
Methods
Study design and data source
Data were derived from the Adelphi Real World HCM Disease Specific Programme (DSP; Adelphi Group, London, UK), a cross-sectional survey of cardiologists and their consulting patients, with elements of retrospective data collection. The HCM DSP was conducted in Italy, Spain, and the US between July 2022 and October 2024. The DSP methodology has previously been describedCitation39,Citation40, validatedCitation41, and demonstrated to be representative and consistent over timeCitation42.
Physicians were recruited by local fieldwork agencies using publicly available information, and, following completion of an eligibility screener survey, were requested to return data on up to ten consecutively consulting patients with HCM; six with oHCM and four with nHCM. Physicians reported data, including demographic and clinical details, as well as HCRU data, using an online patient record form (PRF). PRFs were completed following the patient's consultation and contained questions on both the patient's status at time of survey and retrospective questions on disease history. Physicians could consult the patient's medical records during completion of the PRF to support accurate data return, particularly for retrospective questions. For categorical variables, physicians were presented with a pre-defined list of options, with, where appropriate, the option to select a write-in option. For numerical variables, physicians could directly enter the required number.
Patients for whom data were returned were then requested to complete a voluntary pen-and-paper questionnaire containing several standardized patient-reported outcome measures, detailed below.
Eligibility criteria
Physicians were eligible for inclusion if they were a cardiologist responsible for the treatment and management of patients with HCM and consulted at least five patients with HCM in a month.
Patients were required to be at least 18 years of age and have a physician-confirmed diagnosis of HCM. Patients recruited in Italy and Spain were additionally required to be symptomatic (defined as NYHA class II or above) at time of survey. The only exclusion criterion for patients was participation in a clinical trial at the time of survey.
Physician-reported outcome measures
Physicians reported patients' demographic and clinical characteristics. Demographic characteristics included age, biological sex, ethnicity, employment status, and living circumstances. Clinical characteristics included NYHA class, time since diagnosis, clinical measures, symptoms, concomitant conditions, and physician-perceived risk of hospitalization and death due to HCM.
HCRU measures included healthcare professionals (HCPs) involved in care, HCM-related hospitalization rates and durations (including emergency room use) and reasons for hospitalization, number of tests required for monitoring HCM (blood tests, scans, or physical observations), and caregiver requirements.
Patient-reported outcome measures
Patients completed the KCCQ-23, the EQ-5D-5L questionnaire and Visual Analogue Scale (EQ-VAS), and the Work Productivity and Activity Impairment (WPAI) outcome measures.
The KCCQ-23 is a validated 23-item questionnaire on physical limitations, symptoms (frequency, severity, and recent change over time), social limitations, self-efficacy, and quality of life, with all items measured on a Likert scale with five to seven response optionsCitation13. Summary scores are scaled from 0 to 100, with higher scores indicating better health status. Here, clinical summary scores (CSS) and overall summary scores (OSS) are reported.
Patient HRQoL was assessed using the EQ-5D-5L and EQ-VASCitation43. EQ-5D-5L utility values were calculated using the US tariffCitation44, with a score of 1 indicating perfect health and a score of 0 being equivalent to death. EQ-VAS scores range from 0 to 100, with 100 indicating optimal HRQoL.
Work and activity impairment was assessed with the WPAI in four domains: absenteeism (work time missed), presenteeism (impairment at work), overall work impairment, and activity impairment (regular activities other than work)Citation45. Questions about work impairment were answered only by employed patients; activity impairment questions were answered by all patients. Scores range from 0 to 100 and are expressed as impairment percentages, with higher scores indicating greater impairment.
Statistical analysis
HCM patient data were stratified by NYHA class (I, II, or III/IV) and KCCQ-CSS quartiles. KCCQ-CSS quartiles were determined based on score distributions in the DSP population, and were >0 to ≤70, >70 to ≤83, >83 to ≤92, or >92 to ≤100. The correlation of continuous and ordinal outcomes with NYHA class or KCCQ-CSS was assessed with Spearman's rho; association of outcomes with these ordered groups was compared using the Mann-Whitney U test for dichotomous variables and the Kruskal-Wallis test otherwise.
Patient data were additionally stratified by HCM subtype (oHCM and nHCM) as per physician-reported diagnosis, biological sex (male or female), and country in which the patients consulted (Italy, Spain, or US). These analyses were not further stratified by disease progression measures (NYHA class or KCCQ-CSS quartiles) to preserve adequate sample size within subgroups. For these stratifications, continuous variables were compared using Student's t-tests. Ordered categorical variables were compared using Mann-Whitney U tests for two-group comparisons and Kruskal-Wallis tests for three-group comparisons, and nominal categorical variables were compared using Fisher's exact test, where possible, and chi-squared tests otherwise.
A p-value of 0.05 was considered significant throughout. No adjustment for multiple comparisons was performed due to the highly correlated nature of many outcome measures, increasing the risk of type II errors. Continuous data are shown as means with standard deviations (SDs), while categorical data are shown as counts with proportions. Missing data were not imputed, and group sizes are reported for each individual variable. All statistical analyses were performed using Stata/MP (version 18.5; StataCorp LLC, College Station, TX).
Ethical approval
Data were collected such that physicians and patients could not be identified directly; all data were aggregated and de-identified before receipt. Patients provided informed consent to take part in the survey using a check box. Data collection was conducted in accordance with relevant market research and privacy regulations (EphMRA guidelines)Citation46 and the US Health Insurance Portability and Accountability Act 1996Citation47, and performed in accordance with the principles stated in the Declaration of Helsinki 1967 and subsequent revisions. Exemption from ethical approval was granted by the Pearl Institutional Review Board (IRB number: #22-ADRW-144).
Results
Patient demographic and clinical characteristics
In total, 177 physicians (Italy: n = 60; Spain: n = 58; US: n = 59) returned data on 1,909 patients with HCM (Italy: n = 608; Spain: n = 600; US: n = 701). Of these patients, 286 completed patient surveys (Italy: n = 61; Spain: n = 107; US: n = 118).
Demographic characteristics of included patients stratified by NYHA class and KCCQ-CSS quartile are shown in Table 1, and characteristics stratified by HCM subtype, biological sex, and country are shown in Supplementary Table S1. Overall, the mean age was 56.5 ± 14.8 years, and 60.7% were male. Older patient age was significantly associated with higher NYHA class and lower KCCQ-CSS (p < 0.001). Most patients in Italy/Spain (95.4%, n = 1,153) and the US (70.0%, n = 491) were White. Patients were most commonly working full time (45.3%, n = 831) or not working due to retirement (32.8%, n = 602), though employment status differed significantly by NYHA class and KCCQ-CSS quartile.
Table 1. Physician-reported patient demographic characteristics at time of survey, stratified by NYHA class and KCCQ-CSS quartile.
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Clinical characteristics of included patients stratified by NYHA class and KCCQ-CSS quartile are shown in Table 2, and characteristics stratified by HCM subtype, biological sex, and country are shown in Supplementary Table S2. At time of survey, most patients (78.3%, n = 1,494) were NYHA II functional class, which demonstrated an inverse correlation to higher KCCQ-CSS (p < 0.001). Half of patients (50.4%) had undergone genetic testing related to their HCM, with most being positive for a known HCM-associated gene variant (47.7%) or a likely HCM-associated gene variant (17.1%), with 24.1% having no identified variant. The mean time since diagnosis was 2.8 ± 3.7 years, with increasing time since diagnosis correlating to worsening disease burden as measured by NYHA class (p < 0.001) and KCCQ-CSS quartile (p = 0.004).
Table 2. Physician-reported patient clinical characteristics at time of survey, stratified by NYHA class and KCCQ-CSS quartile.
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Half of the HCM patients (51.4%, n = 609) had a provocable obstruction, with a decreasing proportion with increasing NYHA class (p < 0.001), and varying significantly by country. Mean end-diastolic left ventricular wall thickness at time of survey was 17.6 ± 7.8 mm and mean ejection fraction was 60.7 ± 9.4%; both associated with higher NYHA class and lower KCCQ-CSS quartile.
The most common symptoms at time of survey were dyspnea when active (85.4%, n = 1,540), fatigue or weakness (35.1%, n = 634), and palpitations (28.4%, n = 513). The prevalence of all commonly reported symptoms other than dizziness varied by NYHA class, while the prevalence of fatigue, chest pain when active, dyspnea at rest, and edema varied significantly by KCCQ-CSS.
Most patients had concomitant cardiovascular conditions at time of survey. The specific cardiovascular concomitant condition, or its absence, varied significantly by NYHA class and KCCQ-CSS quartile. The most commonly recorded concomitant cardiovascular conditions in the overall cohort were hypertension (32.0%, n = 320), atrial fibrillation or flutter (19.6%, n = 375), and hyperlipidemia (14.7%, n = 280). Most patients (85.8%, n = 1,637) received treatment for their HCM, though this was significantly different (p < 0.001) between NYHA classes.
Although physicians perceived the risk of hospitalization and death due to HCM in the next 12 months to be low (38.0%, n = 725 and 35.7%, n = 682, respectively) for most patients, these perceptions varied significantly by NYHA class and KCCQ-CSS quartile (p < 0.001 for both).
HCRU
Patients' HCRU stratified by NYHA class and KCCQ-CSS quartile is shown in Table 3, with HCRU stratified by HCM subtype, biological sex, and country shown in Supplementary Table S3. The physicians most commonly involved in HCM management were general cardiologists (81.5%, n = 1,555) or invasive/interventional cardiologists (15.3%, n = 292). The most commonly prescribed treatments in the overall cohort were beta blockers (88.4%, n = 1,447), diuretics (31.8%, n = 521), and calcium channel blockers (31.1%, n = 509). Prescription rates for most treatments varied significantly by NYHA class and KCCQ-CSS quartile.
Table 3. Physician-reported treatment and HCRU, stratified by NYHA class and KCCQ-CSS quartile.
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A quarter of patients (25.8%, n = 405) had an HCM-related hospitalization since diagnosis, averaging 1.6 ± 1.2 admissions, varying by NYHA class and KCCQ-CSS quartile (p < 0.001). In the 12 months before the survey, 13.0% (n = 196) were hospitalized, with a mean of 1.2 ± 0.5 admissions; the average time since the most recent hospitalization was 7.0 ± 3.4 months. Hospitalizations were most often due to worsening HCM symptoms (46.3%, n = 88), surgery (35.8%, n = 68), or HCM complications (31.1%, n = 59), differing by NYHA class: worsening symptoms and complications predominated in NYHA III/IV, while surgery was more common in NYHA I/II.
In the 12 months prior to the survey, patients had an average of 4.2 ± 3.0 HCP visits, with lower KCCQ-CSS quartiles linked to more visits (p < 0.001). Overall, 20.3% required a caregiver, averaging 11.3 ± 27.8 h/week, varying by NYHA class and KCCQ-CSS quartile.
HRQoL and disease impact
Patient-reported HRQoL and disease impact stratified by NYHA class and KCCQ-CSS quartile are shown in Figures 1 and 2, with outcomes stratified by HCM subtype, biological sex, and country shown in Supplementary Figures S1-S3. Mean KCCQ-CSS in the overall cohort was 79.2 ± 17.4 (Figure 1a), with scores significantly decreasing with increasing NYHA (p < 0.001). Mean KCCQ-OSS was 77.6 ± 17.7 (Figure 1b). KCCQ-OSS decreased significantly with increasing NYHA class (p < 0.001) and decreasing KCCQ-CSS quartiles (p < 0.001). Patients' mean EQ-5D-5L utility value was 0.85 ± 0.16 (Figure 1c), with higher NYHA class and lower KCCQ-CSS quartile being associated with lower utility values (p < 0.001 for both). EQ-VAS values showed a similar pattern, with an overall cohort score of 75.0 ± 15.2 (Figure 1d), and significantly lower scores in higher NYHA classes and lower KCCQ-CSS quartiles (p < 0.001 for both).
Figure 1. Patient-reported HRQoL measures in the overall cohort, stratified by NYHA class and KCCQ clinical summary score quartile. (a) KCCQ clinical summary scores. (b) KCCQ overall summary scores. (c) EQ-5D-5L utility values. (d) EQ-VAS score. Data shown as means with SDs. Correlations were assessed using Spearman's rho. Abbreviations: EQ-VAS, EuroQol Visual Analogue Scale; HRQoL, health-related quality of life; KCCQ, Kansas City Cardiomyopathy Questionnaire; NYHA, New York Heart Association.
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Multi-panel bar charts summarizing KCCQ clinical and overall scores, and EQ-5D-5L utility and EQ-VAS scores by NYHA class and KCCQ clinical score quartile.
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Figure 2. Patient-reported work and activity impairment, stratified by NYHA class and KCCQ clinical summary score quartile. (a) Absenteeism. (b) Presenteeism. (c) Overall work impairment. (d) Overall activity impairment. Data shown as means with SDs. Correlations were assessed using Spearman's rho. Abbreviations: KCCQ, Kansas City Cardiomyopathy Questionnaire; NYHA, New York Heart Association; WPAI, Work Productivity and Activity Impairment.
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Four bar charts showing Work Productivity and Activity Impairment, including absenteeism, presenteeism, work impairment, and activity impairment percentages, across NYHA class and KCCQ quartile groups.
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Patients reported a low level of absenteeism in the WPAI questionnaire, at 1.6 ± 6.1% (Figure 2a). Overall presenteeism was 15.4 ± 19.6% (Figure 2b). Overall work impairment for the overall cohort was 16.1 ± 20.9% (Figure 2c). Absenteeism, presenteeism, and overall work impairment increased significantly in lower KCCQ-CSS quartiles. Overall activity impairment, including those not in employment, was 26.6 ± 23.6% (Figure 2d), increasing significantly with higher NYHA class and lower KCCQ-CSS quartile (p < 0.001 for both).
Subgroup analyses by HCM subtype (oHCM and nHCM), sex, and country are presented in the Supplementary Materials. Our data indicate a higher HCRU in patients with both oHCM and nHCM. A greater proportion of female patients experienced HCM-related hospitalizations compared with male patients. Notably, significant differences in HCRU were observed across countries (Supplementary Table S3). EQ-5D-5L scores did not differ by HCM subtype or country; however, female patients reported significantly lower EQ-5D-5L utility values than male patients. No significant differences were observed in absenteeism, presenteeism, or overall work impairment across subgroups (Supplementary Figures S2 and S3).
Discussion
To date, few studies have investigated the real-world HCRU and patient impact of HCM. Here, we use a multinational cohort to show that, despite receiving treatment, patients have a substantial remaining symptom burden and HCRU, particularly so in patients with more severe disease. Patients with more severe HCM also have a notable impact on their HRQoL and impairment in work and activities.
Most patients in the cohort received treatment. The study demonstrates that physicians adapt treatment based on disease severity, with patients with less severe disease most commonly receiving calcium channel blockers and patients with more severe disease receiving diuretics and angiotensin-converting enzyme inhibitors. Previous work in Spain also found differences in prescribing by NYHA classCitation48. Our study found between-country differences in all treatment classes despite both EuropeanCitation49 and USCitation50 treatment guidelines predominantly recommending use of beta blockers and calcium channel blockers. A third of the patients in our study, particularly in the US, received diuretics even though this treatment option is only recommended for patients with concomitant heart failure, which was rare in our cohort, or in patients with fluid overload. Further investigation into differences in treatment practices across countries and disease severity is warranted to better understand these findings.
Use of mavacamten was low in this cohort, likely to it being a recently-approved therapy in the US at time of survey, and only gaining EMA approval mid-way through the survey. While there is a discrepancy in current treatment guidelines regarding the use of mavacamten, as the US treatment guidelines predate its introduction, it is likely it will become a more commonly used second-line treatment, in line with current European guidance. As such, targeted therapies will become more widely used, the treatment patterns and future HCRU (especially those related to invasive septal therapies) may significantly shift from the current findings.
Despite receiving treatment, patients continued to have a notable symptom burden in line with previously published data in oHCM in the USCitation29. Our data suggest patients with more severe disease likely have a higher remaining disease burden. This residual symptom burden is likely to adversely impact patient HRQoL and work and activity impairment, highlighting the need for more efficacious treatment that better addresses patient disease burden.
Along with their residual symptom burden, patients also had a remaining HCRU requirement. Patients with more severe disease had a greater HCRU requirement, including a greater need for hospitalization, at a greater frequency, and HCP consultations, as well as differences in emergency care and ICU need. Previous work has shown a higher number of hospitalizations and higher healthcare costs in patients with higher NYHA classCitation33,Citation51. Our data build on this work, showing this is the case for all patients with HCM, and for a wider range of HCRU measures. Our data also show a greater HCRU need in patients with oHCM and nHCM. Although previous work has shown significant HCRU in patients with oHCMCitation29-31, here we show for the first time that patients with nHCM continue to have a notable HCRU need.
Overall, we found little difference between male and female patients, except for their HCRU usage. A greater proportion of female patients required hospitalization, either at any time in their HCM disease history or in the 12 months prior to the survey. While the reasons for this remain largely unclear, this is in line with previously reported data in both oHCMCitation52 and nHCMCitation53. Female patients in this cohort were older and had a greater proportion of oHCM, which may contribute to their greater HCRU needs.
A fifth of patients also required a caregiver, particularly so in patients with more severe disease. Little is known in the literature about caregiving burden in HCM, though the important role of informal caregivers has been recognized in other chronic cardiovascular conditions, such as heart failureCitation54. Given that caregiving is associated with significant social, economic, and emotional burden, improving patient outcomes to minimize their daily care needs should be a priority.
Beyond the direct medical impact of symptom burden and HCRU requirement, our data also showed evidence of an impact on patients' overall HRQoL. Patient HRQoL, as assessed by KCCQ, varied significantly between disease severity groups, with a score range of more than 20 points. In our cohort, although left ventricular ejection fraction remained within the conventionally preserved range (63.5% in NYHA I versus 54.6% in NYHA III/IV), its reduction in more symptomatic patients may suggest early systolic impairment, potentially reflecting progression toward burn-out phase. Such changes may partially explain the observed reduction in HRQoL, in addition to established mechanisms including obstruction and diastolic dysfunction. Given that the minimally important difference in oHCM has been estimated at 5.6 pointsCitation55, the differences observed in our study are likely to be clinically meaningful. This illustrates the profound impact of disease severity on patient HRQoL and further underscores the need for efficacious treatment and to reduce patients' disease severity.
Although EQ-5D-5L utility values in the overall cohort, reflecting general HRQoL, were largely comparable with previously reported data in HCMCitation56 and similar to age-matched population normsCitation57, our data suggest patients with more severe disease had a greater HRQoL impact, similar to previous reports from a Dutch cohortCitation56. Despite the fact that patients with oHCM had a significantly worse disease burden, there was no significant difference in reported EQ-5D-5L values between these groups, in line with previously reported dataCitation56. However, we did find a significantly lower EQ-VAS value in patients with oHCM. Female patients reported significantly lower EQ-5D-5L utility values compared to male patients, which could be due to the older age and higher prevalence of obstruction in this female cohort.
As well as HRQoL impact, our study also found an impact on patients' work and daily activities. To date, the standardized WPAI instrument has not been used to assess this in patients with HCM, making comparisons across countries or conditions difficult. Here we show that, although there was little absenteeism in this cohort, a notable level of presenteeism and overall work impairment was recorded. This is a similar pattern as observed in other chronic cardiovascular conditions, such as heart failureCitation58.
There was a notable association between KCCQ-CSS and level of absenteeism, presenteeism, and overall work impairment, with patients with a lower score, indicating more severe disease, recording higher levels of impact. Notably, this relation was not seen when analyzed by NYHA class, suggesting the patient-reported KCCQ-CSS score may be a more accurate reflection of symptom burden and impact than the physician-reported NYHA class. However, overall activity burden does increase significantly with NYHA class. The fact that we more frequently see significant association of outcome measures with the patient-reported KCCQ score than with the physician-reported NYHA class suggests the former may be a more accurate way of classifying patients than the traditional NYHA class. This has already been noted in other chronic cardiac conditions, such has heart failureCitation17,Citation59. Our data could support more widespread clinical use of patient-reported outcomes such as the KCCQ in HCM care. Optimizing patient treatment and outcomes, particularly in those patients with more severe disease, may contribute to reducing work and activity impairments, along with their associated personal and wider societal economic impacts.
Although this study has many strengths, including the use of a large, well-characterized, multinational cohort and both physician- and patient-reported data, we must acknowledge some limitations. As inclusion in the HCM DSP is at the time of consultation, patients who consult more frequently have a higher likelihood of being included, which may skew our cohort. Inclusion was based on physician judgment, rather than formalized criteria, but this does reflect real-world clinical practice. Although recall bias may have influenced responses, physicians had access to patient medical records while recording retrospective data, and patient-reported data were collected at the time of consultation, with short recall windows, thus minimizing the potential for recall bias. Due to factors such as differences in healthcare systems, the findings in this study may not be generalizable to other countries. Additionally, because no adjustments for multiple comparisons were made, p-values near 0.05 should be interpreted with caution.
In conclusion, our data show significant impact on HRQoL, work productivity, and daily activities as well as remaining symptom burden and HCRU, despite treatment across a commonly applied measure of disease severity in HCM. While patients with more severe disease by NYHA class or KCCQ-CSS score quartile experienced disproportionately greater burden, even those classified as NYHA I experience substantial disease burden and HCRU. Our data highlight the need for treatments that target the underlying pathophysiology of HCM, with the goal of reducing disease severity, lowering HCRU, and improving HRQoL, ultimately reducing the economic and humanistic burden of HCM for patients and healthcare systems.
Transparency
Declaration of financial/other relationships
PG, JB, MB, EF, and SS are employees and shareholders of Cytokinetics, Inc. JJ, LH, SB, and LL are employees of Adelphi Real World. KA has nothing to disclose. YJS has received funding from Bristol Myers Squibb and consulting from Bristol Myers Squibb and Moderna Japan.
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Author contributions
PG developed the study concept and design. PG, JJ, LH, SB, and LL conducted the statistical analyses, contributed to data interpretation and drafted the manuscript. All authors critically revised the manuscript, approved the final version for publication, and agreed to be accountable for all aspects of the work.
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