Evaluation of Cardiac Fibrosis and Subclinical Cardiac Changes in Sickle Cell Children by Magnetic Resonance Imaging, Echocardiography and Serum Galectin-3

Abstract

Cardiovascular complications account for about one third of the premature mortality rate in patients with sickle cell disease (SCD). Underlying this cardiac risk is a progressive cardiomyopathy which is multifactorial. Recently myocardial fibrosis is assumed to be a novel mechanism for cardiac dysfunction. This study aimed to detect cardiac fibrosis and subclinical cardiac changes in sickle cell children by; cardiac magnetic resonance imaging (CMR), Tissue Doppler Echocardiography (TDE) and Galectin-3. Children with SCD were subjected to assessment of cardiac function by TDE and had estimated serum level of Gal-3. Cardiac MRI was used to assess volumes and function by cine sequence, LGE for detection of focal myocardial fibrosis, native T1 mapping and extracellular volume (ECV) for quantification of diffuse myocardial fibrosis as well as CMR T2* for myocardial iron load. Thirty-four childrenwith SCD (mean age 13.32 ± 3.24 years) were enrolled in our study, another thirty-four healthy children served as controls. Although myocardial iron load by T2* was normal, ECV was increased among all cases with mean level 35.41 ± 5.02 %. The mean of ECV was significantly associated with the frequency of VOCs (P= 0.017) and negatively correlated to hemoglobin level (P=0.005). In consistent with ECV, Galectin-3 level was significantly higher among cases when compared to controls (7.75 ± 1.86 ng/ml versus 6.04 ±1.64 ng/ml, p<0.001) with cutoff value over the ROC curve 6.5ng/ml, sensitivity; 82.5 %, specificity; 72.8%. ECV were significantly higher for cases with Tie index > 0.4 by TDI subgroup when compared to ECV of subgroup with Tie index < 0.4 (38.17 ± 4.25 versus 34.43 ± 5.02, P: 0.03*). In conclusion: ECV is a validated CMR parameter to detect and quantify diffuse interstitial myocardial fibrosis in asymptomatic children with SCD. Cardiac fibrosis in SCD children is associated with frequent attacks of ischemic re-perfusion injury and correlated to the severity of anemia rather than myocardial iron load. Tie index by TDE and serum Gal-3 are recommended screening tools.