Use of Advanced Echocardiographic Modalities to Discriminate Preclinical Hypertrophic Cardiomyopathy Mutation Carriers From Non-Carriers

BACKGROUND: It remains challenging to determine which hypertrophic cardiomyopathy (HCM) family members will subsequently develop HCM. Standard 2-dimensional and conventional Doppler echocardiography have been unable to reliably distinguish HCM genotype-positive and phenotype-negative (G+P-) from genotype-negative and phenotype-negative (G-P-) family members. We aimed to determine if advanced echocardiographic modalities can discriminate HCM G+P- from G-P- individuals. METHODS: Comprehensive echocardiography including speckle tracking evaluation of myocardial deformation and color M-mode were performed in 199 participants aged ≥16 years who had undergone genetic testing from families with a known HCM pathogenic variant: 58 G+P-, 39 G-P-, and 102 overt patients with HCM (genotype-positive and phenotype-positive). The primary analysis compared these measures in all G+P- and G-P- individuals. A secondary analysis was undertaken in younger subjects (age ≤40 years). RESULTS: <0.0001) at the optimal cutoff. Similar findings were demonstrated when the analysis was restricted to younger subjects, although in addition to color M-mode velocity propagation and apical rotation, left ventricular ejection fraction was also independently predictive. CONCLUSIONS: In HCM family members, color M-mode velocity propagation and apical rotation provide good sensitivity and specificity for identifying mutation carriers and may represent early disease markers before the onset of hypertrophy. Longitudinal studies involving larger cohorts are required to validate these findings.