Early Changes in Apical Rotation in Genotype Positive Children with Hypertrophic Cardiomyopathy Mutations without Hypertrophic Changes on Two-Dimensional Imaging

Background Hypertrophic cardiomyopathy (HCM) is the most common form of inherited cardiomyopathy. Echocardiography is the mainstay of screening and disease surveillance, and genetic testing has identified a carrier population without hypertrophy. The aim of this study was to investigate whether changes in left ventricular (LV) function are detectable before the advent of hypertrophy. Methods Fourteen children with genotype-positive, phenotype-negative HCM were identified (12 male; median age, 9.14 years; range, 1.91–15.9 years; median weight, 34.6 kg; range, 15–92.1 kg) and compared with age-matched and sex-matched healthy controls. All children underwent full echocardiographic studies using an extensive functional protocol, including two-dimensional dimensions, Doppler tissue imaging, and two-dimensional speckle-tracking echocardiography. Results There were no differences in LV wall thickness, chamber dimensions, length, and shortening fraction between the groups. Doppler tissue imaging in children with HCM demonstrated mildly reduced septal velocities, notably A′ (5.9 cm/sec [range, 4–8.9 cm/sec] vs 6.7 cm/sec [range, 5.2–9.5 cm/sec]; P  = .009). Circumferential and longitudinal strain was similar between groups. Mean apical circumferential deformation was increased in the HCM group (−24.6 ± 3.8% vs −22.2 ± 2.5%, P  = .04). There were significant increases in basal and apical rotation and LV twist in children with HCM, most marked at the apex (11.7 ± 4.4° vs 5.3 ± 2.5°, P  = .0001). On receiver operating characteristic curve analysis, apical rotation > 7° conferred 83% sensitivity and 82% specificity for predicting HCM (area under the curve, 0.919; P  = .0001). Conclusions Increased LV rotation and twist are present in children with genotype-positive, phenotype-negative HCM. Apical rotation on speckle-tracking echocardiography provides good sensitivity and specificity for the prediction of gene-positive HCM and may be a clinically useful early marker of HCM before the onset of hypertrophy.