Early left ventricular abnormalities in children with heterozygous familial hypercholesterolemia

Background. There are few data available on cardiac morphology and function in children with heterozygous familial hypercholesterolemia (FH). Such patients represent a unique clinical model to assess the effect of pure hypercholesterolemia on cardiac morphology and function, excluding the effect of co-morbidities. Speckle tracking echocardiography (STE), a relatively new echo modality, allows to assess myocardial deformation properties. Aim. We sought to define in FH children the preclinical effects of isolated hypercholesterolemia on the cardiovascular system by examining left ventricular (LV) function using STE. Methods. We prospectively studied 90 children (45 FH children and 45 controls, mean age 11±3 years). Results. FH children showed thicker LV walls and significantly higher LV mass indexed for height 2.7 (p=0.0008) and for body surface area (p<0.0001). LV ejection fraction was similar for both groups. Assessment of diastolic function demonstrated a longer deceleration time(p<0.0001), a reduced early diastolic mitral annular velocity (p<0.0001), and higher transmitral early\ early diastolic mitral annular velocity ratio (p=0.0003) in FH children. Longitudinal and circumferential myocardial deformation of the LV were significantly reduced (p<0.0001) whereas radial deformation was increased in FH children (p=0.04) compared to controls. Conclusions. This study demonstrates that hypercholesterolemia is associated with significant LV morphological and functional alterations during childhood. Our findings also suggest that reduction in longitudinal and circumferential deformations is compensated by an increasing radial strain in FH children with normal LV ejection fraction. This study raises the questions of the clinical importance of these findings, and the opportunity for cholesterol lowering therapy. The potential benefits and risks of such treatment at young age need to be addressed in larger and long term studies.