Hematologic determinants of cardiac remodelling and cardiac index in sickle cell disease patients

Abstract

Background: In sickle cell disease (SCD), relationship between cardiac remodeling, cardiac index(CI) and hemoglobin (Hb), red blood cell count (RBC) and fetal hb (HbF) have not been well characterized. Aim(s): Our aims were to study biological determinants of cardiac involvement in SCD and to describe cardiac characteristics during SCD in a large cohort of patients Methods: We interrogated our hospital database including 1780 adult SCD patients to provide new insights on biological determinants of cardiac characteristics in SCD. Inclusion criteria were: homozygous or S-beta0Thalassemia patients having an echocardiography and steady state biological values before hydroxyurea or blood transfusion. Exclusion criteria were patients less than 18 years old and pregnancy. SCD patients were compared with 25 age-matched black healthy subjects. Echocardiography included M-mode, 2D, pulsed Doppler and Left Ventricular tissue Doppler. Result(s): 656 SCD patients were included in the analysis with a mean age of 31 years (25; 40).Compared to control, SCD had significant higher left ventricular diastolic diameter indexed to body surface area (LVEDDind), left atria diameter indexed (LADind), Cardiac Index (CI), and lower left ventricular ejection fraction (LVEF). Systolic pulmonary artery pressure (sPAP) was not different between the two last groups. In SCD, LVEF was not correlated with Hb (P=0.74) whereas CI and LVEDDind were (both R:0.25, P<0.0001). Systolic dysfunction (LVEF<50%) was observed in only 3.4%. There was poor relationship between LVEDD and CI (R=0.15, P=0.01). Patients were divided in quartiles of CI and LVEDDind. Patients in the fourth quartiles (Q4) of LVEDDind (median/range : 35 (34; 37)) and of CI (4.7 (4.5; 5.3)) versus the three others quartiles (Q1-3) had significantly lower Hb, HbF and RBC, and higher lactate dehydrogenase, bilirubin and Dense Red Blood Cells (DRBC). Determinants of Q4 LVEDDind and CI using multivariate binomial regression analysis were respectively lower Hb and HbF and lower RBC and HbF. Patients with two alpha-thalassemia gene deletions had a significant lower CI and LVEDD. Summary / Conclusion(s): In SS and S-beta0Thalassemia SCD, cardiac remodeling and elevated cardiac output are determined by hematologic variables associated with the "hyper-hemolytic phenotype".