Background It is a challenging goal to identify which family members of patients with hypertrophic cardiomyopathy (HCM) will subsequently develop HCM. Previous studies evaluating the utility of two-dimensional conventional Doppler echocardiography in HCM families with a known pathogenic variant identified on genetic testing have been unable to reliably distinguish preclinical genotype-positive, phenotype-negative (G+P−) individuals from their healthy genotype-negative, phenotype-negative (G−P−) relatives.

Purpose To determine if advanced echocardiographic modalities can discriminate preclinical HCM mutation carriers (G+P−) from non-carriers (G−P−).

Methods A total of 199 participants who had undergone genetic testing from HCM families with a known pathogenic variant were included in the study: 39 G−P−; 58 G+P− and 102 overt HCM patients (G+P+). Speckle tracking echocardiography (STE) and colour M-mode were performed on all participants and longitudinal, circumferential and radial strain, and torsion were compared.

Results Patients with overt HCM had the highest septal, posterior wall thickness, septum/posterior wall (Sep/PW) thickness ratio and left ventricular outflow tract (LVOT) gradient and lowest global longitudinal, circumferential and radial strain, and tissue Doppler-derived myocardial systolic and diastolic velocities. Comparing G−P− and G+P− individuals, there were no significant differences in LV cavity size, wall thickness, LVOT gradient, LVEF and tissue Doppler-derived myocardial systolic and diastolic velocities. However, G+P− individuals had significantly higher peak apical rotation, peak twist and colour M-mode flow propagation velocity (Vp). Multivariate linear regression identified two independent predictors (peak apical rotation and Vp), and a regression equation (using multivariate linear regression) {Mutation carrier prediction value = (0.210×peak apical rotation) − (0.002×Vp) + 0.156; r=0.655)} was derived which allowed reliable discrimination of G+P- individuals with a sensitivity of 95.2% and specificity of 94.1% at the optimal cut-off.

Conclusion In HCM family members without overt HCM, peak apical rotation and Vp provide good sensitivity and specificity for identifying mutation carriers and may be a clinically useful early marker of HCM before the onset of hypertrophy. Future longitudinal studies involving larger cohorts are required to validate these findings.

Funding Acknowledgement Type of funding sources: None.