No abstract

Background-Unexplained left ventricular hypertrophy (LVH) is considered diagnostic of hypertrophic cardiomyopathy (HCM) but fails to identify all genetically affected individuals. Altered diastolic function has been hypothesized to represent an earlier manifestation of HCM before the development of LVH; however, data regarding the clinical utility of imaging techniques that assess this parameter are limited. Methods and Results-Echocardiographic studies including Doppler tissue imaging (DTI) were performed in a genotypedHCM population with ␤-myosin heavy chain (␤-MHC) mutations. Genotype (ϩ) individuals with LVH (Gϩ/LVHϩ; nϭ18) and genotype (ϩ) individuals without LVH (Gϩ/LVHϪ; nϭ18) were compared with normal control subjects (nϭ36). Left ventricular ejection fraction (EF) was significantly higher in both genotype (ϩ) groups (75Ϯ5% and 71Ϯ6%, respectively, versus 64Ϯ5% in control subjects; PϽ0.0001). Mean early diastolic myocardial velocities (Ea) were significantly lower in both genotype (ϩ) subgroups, irrespective of LVH (PϽ0.02). However, there was substantial overlap in Ea velocities between the Gϩ/LVHϪ and control groups. An Ea velocity of Յ13.5 cm/s had 86% specificity and 75% sensitivity for identifying genotype-positive subjects. The combination of EF Ն68% and Ea velocity Ͻ15 cm/s was 100% specific and 44% sensitive in predicting affected genotype. Conclusions-Abnormalities of diastolic function assessed by Doppler tissue imaging precede the development of LVH in individuals with HCM caused by ␤-MHC mutations. Although Ea velocity alone was not sufficiently sensitive as a sole diagnostic criterion, the combination of Ea velocity and EF was highly predictive of affected genotype in individuals without overt manifestations of HCM.