Genotypes and Longitudinal Change in the Cardiac Function in Patients with Suspected Idiopathic Cardiomyopathy

Objective　The relationship between genotypes and longitudinal changes in the comprehensive cardiac function and biomarkers in patients with idiopathic cardiomyopathy has not yet been fully elucidated.Methods　Patients with suspected idiopathic cardiomyopathy who underwent genetic testing for cardiomyopathy-related genes were included. Comprehensive echocardiographic parameters and biomarkers at the initial examinations and final follow-ups were analyzed based on the genotypes.Results　Genetic testing was conducted on 123 patients, identifying variants in the lamin A/C (LNMA) in 16 patients (13%), titin (TTN) in seven patients (6%), and other cardiomyopathy-related genes in 16 patients (13%). No genetic variants were detected in 84 patients (68%). Follow-up echocardiography was performed in 110 (89%) of 123 patients. While patients with TTN truncating variants had a significantly lower baseline left ventricular ejection fraction (LVEF), a significant improvement was observed during the follow-up (31 to 55%, p=0.008). There were no significant differences in the baseline parameters of right ventricular function among the genotypes. However, patients with LMNA variants showed a significantly larger right ventricular end-diastolic area (p=0.035), inferior vena cava diameter (p=0.047), and a higher prevalence of moderate or severe tricuspid regurgitation (p＜0.001) at follow-up than those without. Cardiovascular composite events tended to occur most frequently in patients with LMNA variants (n=6, 38%), whereas no events were observed in patients with TNN variants (p=0.161). Patients with TTN truncating variants had a low baseline LVEF and a favorable response to treatment.Conclusion　Patients with LMNA variants showed no improvement in the left heart function, with right ventricular enlargement and worsening tricuspid regurgitation, suggesting progression to right-sided heart failure.