Gene-Echocardiography: Refining Genotype-Phenotype Correlations in Hypertrophic Cardiomyopathy

Eur Heart J Cardiovasc Imaging. 2023 Aug 10:jead200. doi: 10.1093/ehjci/jead200. Online ahead of print.


Aims: This study aims to clarify the association between hypertrophic patterns and genetic variants in hypertrophic cardiomyopathy (HCM) patients, contributing to the advancement of personalized management strategies for HCM.

Methods and results: A comprehensive evaluation of genetic mutations was conducted in 392 HCM-affected families using Whole Exome Sequencing. Concurrently, relevant echocardiographic data from these individuals were collected. Our study revealed an increased susceptibility to enhanced septal and interventricular septal thickness in HCM patients harboring gene mutations compared to those without. Mid-septal hypertrophy was found to be associated predominantly with MYBPC3 variants, while a higher septum-to-posterior wall ratio correlated with MYH7 variants. Mutations in MYH7, MYBPC3, and other sarcomeric or myofilament genes (TNNI3, TPM1, TNNT2) showed a relationship with increased hypertrophy in the anterior wall, interventricular septum, and lateral wall of the left ventricle. In contrast, ALPK3-associated hypertrophy chiefly presented in the apical region, while hypertrophy related to TTN and OBSCN mutations exhibited a uniform distribution across the myocardium. Hypertrophic patterns varied with the type and category of gene mutations, offering valuable diagnostic insights.

Conclusion: Our findings underscore a strong link between hypertrophic patterns and genetic variants in HCM, providing a foundation for more accurate genetic testing and personalized management of HCM patients. The novel concept of "gene-echocardiography" may enhance the precision and efficiency of genetic counseling and testing in HCM.

Keywords: echocardiography; genotype; hypertrophic cardiomyopathy; phenotype.