Early identification of mutation carriers in familial hypertrophic cardiomyopathy by combined echocardiography and tissue Doppler imaging

Preliminary studies suggested that tissue Doppler imaging (TDI) was able to identify mutation carriers in familial hypertrophic cardiomyopathy (HCM) before the development of hypertrophy. However, data are limited. We performed a systematic analysis of echocardiography, TDI, and electrocardiogram (ECG) in familial HCM to identify parameters associated with genetic status. We analysed 120 adults spread out in three groups: HCM patients with hypertrophy (LVH+, n = 48), mutation carriers without hypertrophy (LVH-/G+, n = 24), and normal control subjects (n = 48). Several parameters were significantly different in LVH-/G+ compared with controls. Multivariate logistic regression identified only three independent echographic/TDI parameters associated with genetic status: the inter-ventricular septum/left posterior wall ratio (P = 0.006), relative wall thickness (P = 0.026), and septal E/Ea ratio (P = 0.008). An echo/TDI score determined after receiver operating characteristic analysis identified mutation carriers with 67% sensitivity and 96% specificity. In comparison, only 29% were identified by the previously proposed TDI criterion (lateral Ea velocity < 14 cm/s) and only 33% by major ECG abnormalities. Tissue Doppler imaging velocities alone were not reliable enough to identify LVH-free mutation carriers in HCM. In contrast, abnormal LV remodelling was a frequent early manifestation of HCM. We developed a new score, combining echocardiographic and TDI parameters, that identifies mutation carriers before and independently of hypertrophy with high accuracy.