Clinical Profile and Health Disparities in a Multiethnic Cohort of Patients With Hypertrophic Cardiomyopathy

Abstract

Background: Clinical studies of hypertrophic cardiomyopathy are over-represented by individuals of European ethnicity, with less known about other ethnic groups. We investigated differences between patients in a multiethnic Australian hypertrophic cardiomyopathy population. Methods: We performed a retrospective cohort study of 836 unrelated hypertrophic cardiomyopathy probands attending a specialized clinic between 2002 and 2020. Major ethnic groups were European (n=611), East Asian (n=75), South Asian (n=58), and Middle Eastern and North African (n=68). The minor ethnicity groups were Oceanian (n=9), People of the Americas (n=7), and African (n=8). One-way ANOVA with Dunnett post hoc test and Bonferroni adjustment were performed. Results: Mean age of the major ethnic groups was 54.9±16.9 years, and 527 (65%) were male. Using the European group as the control, East Asian patients had a lower body mass index (29 versus 25 kg/m 2 , P <0.0001). South Asians had a lower prevalence of atrial fibrillation (10% versus 31%, P =0.024). East Asians were more likely to have apical hypertrophy (23% versus 6%, P <0.0001) and Middle Eastern and North African patients more likely to present with left ventricular outflow tract obstruction (46% versus 34%, P =0.0003). East Asians were less likely to undergo genetic testing (55% versus 85%, P <0.0001) or have an implantable cardioverter-defibrillator implanted (19% versus 36%, P =0.037). East Asians were more likely to have a causative variant in a gene other than MYBPC3 or MYH7 , whereas Middle Eastern and North African and South Asians had the highest rates of variants of uncertain significance (27% and 21%, P <0.0001). Conclusions: There are few clinical differences based on ethnicity, but importantly, we identify health disparities relating to access to genetic testing and implantable cardioverter-defibrillator use. Unless addressed, these gaps will likely widen as we move towards precision-medicine–based care of individuals with hypertrophic cardiomyopathy.

Alpha-protein kinase 3 (ALPK3) truncating variants are a cause of autosomal dominant hypertrophic cardiomyopathy

“…When stratifying the enrichment analysis for ethnicity in the discovery cohort, the OR for South Asians was 44.75 compared to 10.92 in whites. This observation must be confirmed in other cohorts, but it is of potential relevance as some non-white cohorts including South Asians tendentially show a larger prevalence of genotype elusive (VUS and genotype negative) patients, 26 where the discovery of novel causal genes would have a significant clinical impact.…”

Evolving Contemporary Management of Atrial Fibrillation in Hypertrophic Cardiomyopathy

“…3,4,22 Although in the general population AF is more prevalent in men, no difference with respect to sex is evident in HCM (Table 1), nor is there a difference in AF prevalence in regions of the world. 4,12,17,[23][24][25][26] However, risk for AF appears to be lower in Black versus White patients with HCM. 27,28 The overall burden of AF in the HCM population is likely underestimated because most reports include only clinically identified patients who are predominantly symptomatic.…”

The Need for Inclusive Genomic Research

“…In large part due to a lack of ancestry-matched population reference data, individuals from diverse ancestry groups are less likely to receive an informative genetic result, that is, where a pathogenic or likely pathogenic variant is identified as the cause of disease. 9–11 As such, interpretation of variants becomes fundamentally challenging, resulting in a larger burden of variants of uncertain significance. In the study by Tomar et al, 2 variants previously classified as pathogenic were identified in the SG10K cohort: MYBPC3 p.Glu334Lys was observed in 13 of 4810 (0.03%) and SCN5A p.Asp1819Asn was observed in 13 of 4810 (0.03%).…”

“…In large part due to a lack of ancestry-matched population reference data, individuals from diverse ancestry groups are less likely to receive an informative genetic result, that is, where a pathogenic or likely pathogenic variant is identified as the cause of disease. [9][10][11] As such, interpretation of variants becomes fundamentally challenging, resulting in a larger burden of variants of uncertain significance.…”