Differences in Characteristics and Outcomes Between Patients With Hypertrophic Cardiomyopathy From Asian and European Centers.

Hypertrophic cardiomyopathy (HCM) is a common form of inherited cardiomyopathy with a prevalence in the general population reported as 0.2% in different international studies. Although differences in disease expression and outcome are described among White and Black patients with HCM, it is largely unknown whether Asian patients present also a different HCM phenotype. Only 1 study included 133 Asian patients and highlighted health disparities among ethnicities relating to access to genetic testing and implantable cardioverter‐defibrillator (ICDs) use.

In our study, a total of 1661 consecutive patients (1210 European patients; 451 Asian patients including 308 Chinese, 83 Malay, and 60 South Asian patients) diagnosed with HCM according to current criteria were included from 3 centers (Leiden University Medical Center, The Netherlands; National University Hospital, Singapore; Aristoteleio University of Thessaloniki, Greece). This study aimed to evaluate the differences between patients with HCM from the European centers (n=1214, 1% Asian ethnicities) and the Asian center (n=447, 97% Asian ethnicities), to elucidate the influence of ethnicity, differences in care patterns, and sociocultural factors on patient outcome. The institutional review boards approved this retrospective analysis and waived the need for informed consent. The data that support the findings of this study are available from the corresponding author upon reasonable request.

At the time of diagnosis, patients from the Asian center were older than those from the European centers (59 [47-68] years versus 52 [41-62] years, P<0.001), with similar proportion of men (71% versus 67%, P=0.093) and lower body surface area (1.7±0.2 m2 versus 2.0±0.2 m2, P<0.001). Diabetes (22% versus 16%, P=0.004) was more frequent in European centers, whereas hypertension (23% versus 49%, P<0.001) and coronary artery disease (8% versus 28%, P<0.001) were more prevalent in the Asian center. New York Heart Association functional class (class III–IV 7% versus 10%, P=0.096) at presentation was not significantly different between patients from Asian and European centers. By echocardiography, patients from the Asian center presented with smaller septal wall thickness (16 [13-19] mm versus 18 [16-22] mm, P<0.001) but the maximum wall thickness (19 [17-22] mm versus 19 [16-22] mm, P=0.13) and left ventricular mass index (127 [105-166] g/m2 versus 127 [105-160] g/m2, P=0.77) were similar. This observation can be explained by the fact that apical hypertrophy was more frequent in patients from the Asian center (31% versus 13%, P<0.001), whereas patients from the European centers showed significantly more septal hypertrophy with significant left ventricular outflow obstruction (28% versus 17%, P<0.001) and ≥ grade 2 mitral regurgitation (17% versus 10%, P=0.002). In addition, patients from European centers showed slightly lower left ventricular ejection fraction (67 [62-74] % versus 70 [64-76] %, P=0.006), although still within normal range, and higher E/E’ ratio (12 [9-17] versus 11 [8-14], P<0.001). Interestingly, beta blockers were more frequently prescribed in European centers (61% versus 49%, P<0.001), whereas calcium‐channel blockers were more used among patients from the Asian center (25% versus 16%, P<0.001). This difference can be related to the low prevalence of patients with obstructive HCM from the Asian center but also to the reported low tolerance for beta blockers among patients of Asian ethnicities. Similarly, patients from European centers underwent septal reduction therapy more frequently than those from Asian centers (8% versus 0.4%, P<0.001). Genetic testing was overall underused during the diagnostic process and seldom performed at the Asian center (3% versus 17%, P<0.001). This observation may relate to the lack of financial reimbursement in Asia but could also be associated with the observed less frequent family history of HCM (5% versus 39%, P<0.001) and of sudden cardiac death (0.4% versus 24%, P<0.001) in patients from the Asian center. The number of ICDs was significantly lower in the Asian center (2% versus 19%, P<0.001). This may reflect some perceived barriers regarding ICD implantation reported in Asia.

From the first visit, follow‐up duration was 7 (4–14) years. The survival analyses adjusted for age, sex, hypertension, diabetes, and coronary artery disease (as the main clinical characteristics significantly different among the 2 groups) showed that the event rates for the end point overall survival (hazard ratio [HR], 2.35; 95% CI, 1.77–3.12, P<0.001), the combined end point survival and heart failure hospitalization (HR, 2.61; 95% CI, 2.02–3.37, P<0.001), and the combined end point survival and ICD shocks (HR, 1.81; 95% CI, 1.39–2.36, P<0.001) were significantly higher in patients from the Asian center (Figure).

Figure 1

Clinical outcomes in Asian patients vs European patients with hypertrophic cardiomyopathy.

Survival curves adjusted for age, sex, hypertension, diabetes, and coronary artery disease for the end points of (A) Survival, (B) Survival and heart failure hospitalization, and (C) Survival and implantable cardioverter‐defibrillator shocks, according to patients from a European center or Asian center. A–C, Graphical representations of adjusted survival curves derived from regression estimates based on the average covariate values of the study population, illustrating the impact of the increased hazard associated with patients from an Asian center for each end point. HR indicates hazard ratio.

Although limited by its retrospective design, this study shows significant differences in clinical presentation (such as age and comorbidities) and echocardiographic characteristics (obstructive versus apical hypertrophic phenotype) between patients with HCM managed in Asian and European centers. These observations may reflect differences in ethnicity but also sociocultural factors, care patterns, access to care, and/or other social determinants of health. However, owing to the close correlation between ethnicity and center, it was not possible to perform analyses to ascertain causality. Nevertheless, these aspects are important when customizing patient care, including the choice of additional diagnostics (ie, genetic analysis, cardiac magnetic resonance imaging) or of treatment specifically targeting left ventricular obstruction or sudden cardiac death prevention. Finally, the observed differences in clinical presentation and patient management (medication choice and ICD implantation rate) could explain the less favorable outcomes of patients from the Asian center, suggesting the need for improving patient access to care and the application to international guidelines. These findings are representative of patients from only 3 centers and it is hoped they will stimulate future research studies to further explore these observations.

Sources of Funding

The Department of Cardiology of the Leiden University Medical Center received research grants from Abbott Vascular, Bayer, Bioventrix, Medtronic, Biotronik, Boston Scientific, GE Healthcare, and Edwards Lifesciences. Butcher received funding from the European Society of Cardiology (ESC Research Grant App000080404). Hirasawa is financially supported by an ESC research grant (R‐2018‐18122).

Disclosures

Bax received speaker fees from Abbott Vascular. Victoria Delgado received speaker fees from Abbott Vascular, Edwards Lifesciences, GE Healthcare, MSD, and Medtronic. Nina Ajmone Marsan received speaker fee from Abbott Vascular and GE Healthcare and was on the advisory board of Philips Ultrasound. The remaining authors have no disclosures to report.