ACQUIRED HEART DISEASE IN CHILDREN AND YOUNG ADULTS Early Left Ventricular Abnormalities in Children with Heterozygous Familial Hypercholesterolemia Giovanni Di Salvo, MD, PhD, MMSc, FESC, Angelo Fabio D’Aiello, MD, Biagio Castaldi, MD, Bahaa Fadel, MD, Giuseppe Limongelli, MD, PhD, FESC, Antonello D’Andrea, MD, PhD, FESC, Valeria Pergola, MD, Giuseppe Pacileo, MD, Emanuele Miraglia Del Giudice, MD, Laura Perrone, MD, Raffaele Calabr o, MD, and Maria Giovanna Russo, MD, Naples, Italy; Riyadh, Saudi Arabia Background: Few data are 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 hyper- cholesterolemia on cardiac morphology and function, excluding the effect of comorbidities. Speckle-tracking echocardiography, a relatively new echocardiographic modality, allows the assessment of myocardial defor- mation properties. The aim of this study was to define in children with FH the preclinical effects of isolated hypercholesterolemia on the cardiovascular system by examining left ventricular (LV) function using speckle-tracking echocardiography. Methods: Ninety children (45 with FH and 45 controls; mean age, 11 6 3 years) were prospectively studied. Results: Children with FH showed thicker LV walls and significantly higher LV mass indexed for height 2.7 (P = .0008) and for body surface area (P < .0001). LV ejection fractions were similar in both groups. Assessment of diastolic function demonstrated longer deceleration times (P < .0001), reduced early diastolic mitral annular ve- locities (P < .0001), and higher transmitral early/early diastolic mitral annular velocity ratios (P = .0003) in children with FH. Longitudinal and circumferential myocardial deformation of the left ventricle were significantly reduced (P < .0001) whereas radial deformation was increased in children with FH (P = .04) compared with controls. Conclusions: This study demonstrates that hypercholesterolemia is associated with significant LV morpho- logic and functional alterations during childhood. The findings also suggest that reductions in longitudinal and circumferential deformation are compensated for by increasing radial strain in children with FH with nor- mal LV ejection fractions. 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 a young age need to be addressed in larger long-term studies. (J Am Soc Echocardiogr 2012;25:1075-82.) Keywords: Familial hypercholesterolemia, Ventricular function, Children, Speckle-tracking echocardiography The incidence of heterozygous familial hypercholesterolemia (FH) is 1 in 500 births. 1-5 In children with FH, increased low-density lipopro- tein (LDL) cholesterol leads to endothelial dysfunction, adverse changes in vascular morphology, and increased intima-media thick- ness in the peripheral arteries. 6,7 As a consequence, myocardial ischemia due to coronary artery stenosis has been documented in young adults with this disorder. 8,9 Unfortunately, few data are available on cardiac morphology and function in children with FH. A relatively new echocardiographic tech- nique, speckle-tracking echocardiography (STE), allows the assessment of myocardial deformation properties. 10,11 Regional calculations using STE allow the quantification of regional myocardial function in normal children and in children with congenital heart disease. 10-12 Moreover, STE can detect early subclinical myocardial abnormalities in patients with hypertension, 13 diabetes, 14 obesity, 15 and metabolic syndrome, 16 even in the presence of normal left ventricular (LV) ejection fraction. Children with FH, without other comorbidities, represent a unique clin- ical opportunity to evaluate the early effects of hypercholesterolemia, per se, on myocardial function. The detection of early subclinical man- ifestations may have clinical importance, because treatment to reverse the process is most likely to be effective earlier in the disease process. We sought to define in children with FH the preclinical effects of iso- lated hypercholesterolemia on the cardiovascular system by examining LV function using the more sensitive two-dimensionally derived STE. METHODS Patients Children with FH were prospectively enrolled in our pediatric depart- ment. Inclusion criteria were (1) the presence of one parent with From the Second University of Naples, Monaldi Hospital, Naples, Italy (G.D., A.F.D., B.C., G.L., A.D., V.P., G.P., E.M.D., L.P., R.C., M.G.R.); and King Faisal Specialist Hospital and Research Center, Heart Institute, Riyadh, Saudi Arabia (B.F.). Reprint requests: Giovanni Di Salvo, MD, PhD, MMSc, FESC, Second University of Naples, Monaldi Hospital, Via Omodeo 45, 80128 Naples, Italy (E-mail: giodisal@ yahoo.it). 0894-7317/$36.00 Copyright 2012 by the American Society of Echocardiography. http://dx.doi.org/10.1016/j.echo.2012.07.002 1075