Prediction of genetic cardiomyopathy by whole exome sequencing and myocardial strain in patients with concentric left ventricle hypertrophy

Abstract

Abstract Introduction Genetic cardiomyopathies (CMP) are a group of inherited diseases that can lead to heart failure and sudden cardiac death. Left ventricular hypertrophy (LVH) is common findings in these diseases, but the diagnosis can be challenging due to their heterogeneous clinical presentations. Myocardial strain and whole exome sequencing (WES) are a powerful tool for early detection of genetic CMP. Purpose We aim to investigate the utility of the combination of myocardial strain and WES in the diagnosis of genetic CMP in patients with LVH. Methods We performed WES with buccal swab test on a total of 65 patients who had concentric LVH and decreased global average strain (GAS) by echocardiography between July 2021 and December 2022. The genetic data was analyzed to identify disease-causing genetic variants, and the clinical data and echocardiographic findings were collected and analyzed. Logistic regression analysis was performed to identify the predictive factors of genetic cardiomyopathy, and receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic accuracy of these factors. Results Of the 65 patients, we identified 10 patients with genetic cardiomyopathy by WES, including hypertrophic CMP, cardiac amyloidosis, and Fabry disease. The diagnostic yield of WES was 15.4% for genetic CMP. Logistic regression analysis showed that sex, diastolic blood pressure, interventricular septal thickness at end diastole (IVSd) and end systole (IVSs), posterior wall thickness at end diastole (PWd), and GAS were significant predictors of genetic CMP (p<0.05 for all). ROC curve analysis showed that IVSs had the highest area under the curve (AUC) value of 0.711 (p=0.037), with a sensitivity of 60.0% and a specificity of 67.3%. Conclusion Our study highlights the utility of WES and myocardial strain with echocardiographic data in diagnosing genetic CMP, especially in patients with concentric LVH. These findings support the integration of genetic testing and advanced imaging techniques in the diagnostic approach for patients with suspected genetic cardiomyopathies.