Subclinical echocardiographic abnormalities in phenotype-negative carriers of myosin-binding protein C3 gene mutation for hypertrophic cardiomyopathy

Background Early diastolic myocardial tissue Doppler velocities have reported to be reduced in mutation-positive patients with hypertrophic cardiomyopathy (HCM) in some studies even in the absence of left ventricular hypertrophy (LVH). Strain is a sensitive tool in detecting early systolic abnormalities in patients with HCM. Our goal is to examine novel echocardiographic characteristics of phenotype-negative carriers for a known sarcomeric gene mutation for HCM. Methods We evaluated 41 consecutive subjects with a known myosin-binding protein C3 (MYBPC3) mutation (c.3330+ 2T>G). Subjects who were mutation positive without LVH (G+/LVH-, n = 35) were compared with healthy controls (n = 30) regarding tissue Doppler and segmental longitudinal strain measures. Results The G+/LVH-group was similar to the healthy controls with respect to chamber size, left ventricular mass index, and most diastolic filling parameters, including tissue Doppler-derived early diastolic annular velocities. Global longitudinal strain was similar for both groups (20.3 +/- 2.1 vs 19.8 +/- 1.8, P = .36), although regional segment analysis showed a notable reduction in the basal septum (16.8 +/- 3.1 vs 19.0 +/- 4.0%, P = .02) and increase in the basal posterior (22.5 +/- 5.2 vs 17.9 +/- 5.2, P = .001) as well as mid posterior (21.8 +/- 4.7 vs 18.2 +/- 3.0, P = .001) walls. Conclusions In our cohort of phenotype-negative carriers of a specific MYBPC3 mutation, there were minimal differences in conventional 2-dimensional, Doppler, and speckle-tracking-derived parameters of systolic and diastolic function compared with that of healthy subjects. The presence of regional alterations in strain indicative of the presence of underlying subclinical disease requires further validation. (Am Heart J 2011;162:262-267.e3.)