Genetic Architecture of Dilated Cardiomyopathy in Individuals of African and European Ancestry.
Elizabeth Jordan et al. JAMA 2023 8 (5) 432-441
Does the rare variant genetic architecture of dilated cardiomyopathy differ between patients of African and European ancestry? In this cross-sectional study of 1198 patients with dilated cardiomyopathy, significantly fewer patients of African ancestry (8.2%) than those European ancestry (25.5%) had variants classified as pathogenic or likely pathogenic, a difference due in part to fewer predicted loss-of-function variants and less case-based evidence to support pathogenicity for variants found only in patients of African ancestry.
Transthyretin Cardiac Amyloidosis: Underrecognized in the Underrepresented.
Douglas J Leedy et al. J Am Heart Assoc 2023 7 e030802
Over the past decade, transthyretin cardiac amyloidosis (ATTR-CM) has rapidly emerged as an increasingly diagnosed cause of heart failure (HF) among older adults, predominantly those with HF with preserved ejection fraction. Although still frequently classified as a rare disease, there is mounting evidence that ATTR-CM is not as “rare” as it has been historically described. Because of the development of effective disease-modifying therapies, such as transthyretin stabilizers, early and accurate identification of ATTR-CM is essential.
Clinical Penetrance of the Transthyretin V122I Variant in Older Black Patients With Heart Failure: The SCAN-MP (Screening for Cardiac Amyloidosis With Nuclear Imaging in Minority Populations) Study.
Avni Madhani et al. J Am Heart Assoc 2023 7 e028973
Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed cause of heart failure (HF) among patients =60?years of age. Although the V122I (valine to isoleucine substitution at position 122 of the transthyretin protein) variant associated with hereditary ATTR-CM is present in 3.4% of self-identified Black individuals in the United States (or 1.5?million people), the phenotypic penetrance is not known. In this study, among older Black individuals with HF and increased left ventricular wall thickness, of those with ATTR-CM, 63% had wild-type, and of those with V122I, the phenotypic penetrance of ATTR-CM was 39% (95% CI, 17–64), suggesting that genotype alone is insufficient for diagnosis.
EMQN: Recommendations for genetic testing in inherited cardiomyopathies and arrhythmias
JB Hayesmoore et al. EJHG July 13, 2023
Inherited cardiomyopathies and arrhythmias (ICAs) are a prevalent and clinically heterogeneous group of genetic disorders that are associated with increased risk of sudden cardiac death and heart failure. Making a genetic diagnosis can inform the management of patients and their at-risk relatives and, as such, molecular genetic testing is now considered an integral component of the clinical care pathway. However, ICAs are characterised by high genetic and allelic heterogeneity, incomplete / age-related penetrance, and variable expressivity.