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

Aims: 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.
Methods and Results: 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.
Conclusion: 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.