Genetics plays a role in the diagnosis and management of cardiomyopathies. A recent study published in Circulation: Genomic and Precision Medicine investigated the prevalence of pathogenic/likely pathogenic cardiomyopathy gene variants and their association with clinical outcomes in a diverse U.S. population. The findings have implications for genetic screening strategies, particularly within specific ancestry groups.
Study Design and Key Findings
The retrospective cohort study utilized data from the All of Us Research Program, including 167,435 U.S. adults aged years with sequencing data. Pathogenic/likely pathogenic variants in cardiomyopathy genes were identified using the ClinVar database. The primary outcome of interest was heart failure, while secondary outcomes included cardiomyopathy and arrhythmia, all identified from electronic health records.
The study found an overall prevalence of 0.7% for pathogenic/likely pathogenic cardiomyopathy variant carriers in the general population. This prevalence varied among different ancestry groups: 0.8% in individuals of European ancestry, 0.8% in those of African ancestry, 0.5% in East Asian ancestry, and 1.2% in South Asian ancestry individuals.
Carriers of these variants faced a significantly increased risk of adverse cardiovascular outcomes compared to non-carriers:
- Heart failure: Incidence rate of 3.05 per 1,000 person-years in carriers versus 1.37 in non-carriers (adjusted HR 2.30 [95% CI, 2.04-2.60]).
- Cardiomyopathy: Incidence rate of 2.38 per 1,000 person-years in carriers versus 0.54 in non-carriers (adjusted HR 4.31 [95% CI, 3.73-4.97]).
- Arrhythmia: Incidence rate of 3.93 per 1,000 person-years in carriers versus 2.09 in non-carriers (adjusted HR 2.12 [95% CI, 1.78-2.53]).
The authors concluded that despite the modest overall prevalence, the elevated risks associated with these variants suggest potential benefits of targeted genetic screening for early detection and management.
Implications for Black Patients
The study’s findings are particularly relevant for Black patients, as individuals of African ancestry showed a prevalence of 0.8% for pathogenic/likely pathogenic cardiomyopathy variants, aligning with that of European ancestry individuals. This highlights that a significant proportion of Black patients carry these genetic variants, putting them at an increased risk for heart failure, cardiomyopathy, and arrhythmias.
While the study did not specifically delve into the unique challenges or implications for Black patients beyond reporting prevalence rates, the data underscores the importance of considering genetic factors in their cardiovascular care. Inherited cardiomyopathies are considered underdiagnosed conditions, and with decreasing costs and increasing access to genetic sequencing, there are growing opportunities for improved prevention and treatment through genetic screening.
For Black patients, who disproportionately experience cardiovascular disease, targeted genetic screening could be a crucial tool for early identification and preemptive intervention. The study authors advocate for targeted screening, especially in individuals with existing heart failure, cardiomyopathy, or arrhythmia of unclear origin, where genetic testing may be more efficient and yield higher results. This recommendation holds for Black patients presenting with these conditions.
Furthermore, the concept of cascade screening, where family members of an identified carrier are screened, is strongly supported by the study. Given that the penetrance of cardiomyopathy variants is likely similar within a family, cascade screening could yield actionable results for many Black families affected by these conditions.
Limitations and Future Directions
The study’s limitations include its inability to capture younger individuals who may have experienced sudden cardiac death before enrolling in the All of Us program. Additionally, the reliance on ICD codes for outcome identification could lead to misclassification. The authors also noted that observed differences in variant prevalence by race might be influenced by sample size limitations and variations in the sensitivity and specificity of variant classification methods.
These limitations highlight a critical need for larger, more ethnically diverse cohorts with comprehensive genotype-phenotype data. Such studies are essential to validate ancestry-specific prevalence rates, refine variant classification methods, and gain a deeper understanding of the genetic mechanisms underlying observed differences in various populations, including Black patients.
This study gives valuable insights into the prevalence and clinical impact of pathogenic/likely pathogenic cardiomyopathy variants. For healthcare professionals managing Black patients, these findings emphasize the importance of considering genetic screening as a tool for early detection and management, potentially leading to improved cardiovascular outcomes.