Cardiac involvement in sickle β-thalassemia

Abstract

Cardiovascular involvement is a leading cause of mortality and morbidity in patients with inherited hemoglobinopathies, but it has not been adequately assessed in sickle β-thalassemia. We evaluated 115 sickle β-thalassemia patients, aged 34±14 years, along with 50 healthy controls, by resting echocardiography. Patients with systolic left ventricular (LV) dysfunction or severe pulmonary hypertension (PHT) also underwent left and right cardiac catheterization and cardiac magnetic resonance imaging (CMR). Left and right chamber dimensions, LV mass, and cardiac index were significantly higher in patients compared to controls (p<0.001 in most cases). Three patients (2.9%) had reduced LV ejection fraction (<55%); mean LV ejection fraction was significantly lower in patients (p< 0.001). Left and right ventricular systolic tissue Doppler indices and LV diastolic tissue Doppler indices were also impaired in patients. All three patients with systolic LV dysfunction had normal coronary arteries and mild myocardial iron load (CMR T2* values, 18-25 ms). Systolic pulmonary artery pressure was significantly higher in patients compared to controls (p=0.002); PHT was present in 28 patients (27%), while severe PHT in three (2.9%). In three patients with severe PHT, only one had impaired LV ejection fraction and increased pulmonary wedge pressure. Overall, three patients (2.9%) had a history of heart failure, two with systolic LV dysfunction, and one with severe PHT. Cardiac involvement in sickle β-thalassemia concerns biventricular dilatation and dysfunction along with PHT, leading to congestive heart failure.

Pulmonary Hypertension Associated With Hemoglobinopathies

“…12 In sickle-thalassemia, a compound heterozygous state with 1 thalassemia and 1 sickle allele, PH has been observed with a rather lower frequency and a definitely lesser severity. [15][16][17] It should be stressed that with the exception of thalassemia intermedia, in which PH was confirmed by right-sided heart catheterization in 2 of the previously cited trials, 8,9 the vast majority of studies in thalassemia and sickle cell disease used echocardiography as a screening tool, and therefore, the reported prevalence may be overestimated by at least some of those trials.…”

“…23 In this context, other investigators have found a poor correlation between PH and markers of hemolysis in patients with sickle-thalassemia, in whom a lower hemolytic rate may be present. 16,17 It appears that the relative severity of hemolysis in different hemolytic conditions may determine the degree of its contribution to the development of PH. Regardless, the interaction between hemolysis and nitric oxide depletion is currently beyond doubt because it is supported by the bulk of evidence derived from both experimental and clinical studies.…”

“…6 Left-sided valvular disease has also been encountered at a higher percentage than in normal individuals of similar ages, especially in the form of mitral regurgitation and prolapse. 9,17,35 The main mechanisms involved in the pathogenesis of left-sided heart disease in hemoglobinopathies include high-output state, iron overload, myocarditis, and other immunogenic factors, as well as the aforementioned elastic tissue defect. 1,6,7,9,17,24,30,36 Chronic anemia induces a compensatory high-output state and volume overload.…”

“…9,17,35 The main mechanisms involved in the pathogenesis of left-sided heart disease in hemoglobinopathies include high-output state, iron overload, myocarditis, and other immunogenic factors, as well as the aforementioned elastic tissue defect. 1,6,7,9,17,24,30,36 Chronic anemia induces a compensatory high-output state and volume overload. This is particularly evident in hemoglobinopathies, in which high cardiac output is related to the chronic tissue hypoxia that results from low total hemoglobin levels and increased levels of hemoglobin F, compensatory bone marrow expansion, splenomegaly, and coexistent hepatic injury.…”

Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension: Pulmonary hypertension associated with hemolytic anemia

“…Iron overload not only lead to left heart dysfunction, it also causes liver disease contributing further to the development of PH due to liver cirrhosis. [6424344] In short, the pathobiology of PH in hemolytic disorders is a rainbow of many colors. Mechanisms like NO depletion, dysregulated arginine metabolism, oxidative stress and hypercoagulable state result in pulmonary vasoconstriction, endothelial proliferation and hyperplasia, and in situ thrombi.…”