Echocardiografic Abnormalities in Patients with Sickle Cell/β-Thalassemia Do Not Depend on the β-Thalassemia Phenotype

Introduction: Heart disease represents an important cause of mortality and morbidity in sickle cell disease and beta-thalassemia, however the impairment of cardiac function in compound heterozygotes, namely sickle cell/β-thalassemia (HbS/β-thal) remains less known. Studies with patients of Greek origin demonstrated abnormal diastolic function in both ventricules, with unchanged systolic function, and biventricular dilatation along with pulmonary hypertension (Aessopos, A., et al., Ann Hematol, 88(6), 2009, Moyssakis, I., et al., Postgrad Med J, 81(961), 2005). The aim of this study was to evaluate echocardiographic findings and clinical and laboratory parameters in a cohort of Brazilian HbS/β-thal patients to better understand the cardiac involvement in this particular ethnic background.

Methods: A retrospective chart review was performed on thirty-six HbS/β-thal patients followed from 1998 to 2016. Medical records were reviewed for laboratory and clinical data, and hospital admissions were recorded for sickle related complications: acute chest syndrome, retinopathy, avascular bone necrosis, stroke, priapism, leg ulcers and venous thromboembolism. Echocardiographic evaluation was performed in all patients in steady-state disease, with pulsed, continuous, two-dimensional and color Doppler.

Results: Among the studied population, 21 (58%) were women and 15 (42%) were men. The median age was 38 (18-70) years; 22 (61%) patients were diagnosed as Sβ⁰, and 14 (39%) as Sβ⁺. As expected, when the Sβ-thalassemia phenotype was considered, the two groups of patients differed significantly: hemoglobin levels were lower in Sβ⁰ patients, who also presented a higher proportion of HbS and HbF and higher transferrin saturation indexes. Sβ⁰ patients also demonstrated significantly lower body mass index and higher number of platelets highlighting disease severity in this subgroup of patients. Left atrial (LA) and left ventricular (LV) dilation were found in 19.5 and 11% of patients, respectively. These prevalences are considerably lower than observed in patients with SS phenotype: 78 and 35%, respectively (Damy et al, Eur Heart J, 37(14), 2016). Systolic LV disfunction (defined as LV ejection fraction <59%) was present in only one patient of our cohort, though also uncommon in SS patients (8.5% in the study of Damy et al). There were no significant differences in masses and volumes of cardiac chambers comparing Sβ⁰ with Sβ⁺ patients, and we found no relationship between these parameters and the occurrence of specific complications of the disease. However, a significant correlation was found regarding parameters of myocardial hypertrophy with serum creatinine, hepatic transaminases and bilirubin levels. Moreover, among the 36 patients studied, 3 of them (1 Sβ⁺ and 2 Sβ⁰) presented stroke; these patients were significantly older (median 53 years x 37.5 years, p = 0.048), had higher values of left ventricular posterior wall diastolic thickness [8 (6-14) x 10 (10-11), p= 0.03], greater left ventricular mass [147 (69-537) x 226 (194-260), p= 0.039] and a significantly higher left atrium / aortic ratio (1.26 (0.9-1,48) x 1.545 (1.48-1.61), p= 0.032). No differences were found in pulmonary artery systolic pressure (PASP) between Sβ⁺ and Sβ⁰ patients and there was no relationship between PASP and the occurrence of acute or chronic complications.

Discussion: In this cohort of Brazilian patients, we observed significant differences in hematological and clinical parameters between Sβ⁺ and Sβ⁰ patients, highlighting the difference in disease severity between the two groups. However, the profile of cardiac involvement analyzed by echocardiography was similar in both groups: higher prevalence of diastolic dysfunction with little systolic function impairment, which follows the patterns of the patients of greek origin. Nevertheless, parameters of myocardial hypertrophy were related to multiorgan impairment, and rendered a higher propensity for stroke in older patients. Thus, cardiac involvement in this disease seems to not depend on the thalassemia phenotype. This may also reflect the older age of subjects evaluated, demonstrating that the exposure to the disease features (anemia/hemolysis/inflammation) renders homogeneity in cardiac damage over time, and represents an alert for greater vigilance and control of associated factors, as hypertension and diabetes.