Left Ventricular Dysfunction in Chronically Transused Patients with Sickle Cell Anemia and Thalassemia.
Authors: Neumayr Lynne , Fung Ellen , Harmatz Paul , Butensky Ellen , Wood John , Morris Claudia , Robertson Shanda , Milet Meredith , Vichinsky Elliott 
Published: October 2019

Abstract
BACKGROUND: Iron-induced cardiomyopathy has been extensively described in thalassemia (THAL) patients. Left ventricular (LV) dysfunction is the leading cause of death in THAL, with prevalence estimates ranging from 6% to 23%. Recent MRI techniques confirmed that T2* measurements consistent with elevated cardiac iron are associated with LV dysfunction and early mortality. Transfusion therapy is being increasingly used for the treatment and prevention of complications in sickle cell disease (SCD). By adulthood, the majority of SCD patients will have received multiple transfusions and nearly 1/3 will be iron-overloaded. However, cardiomyopathy, its prevalence, and the role of iron toxicity have not been studied in SCD. The Multicenter Study of Iron Overload, a 5-year prospective natural history study, enrolled 152 transfusion dependent THAL, 204 chronically transfused SCD (txSCD) and 64 control SCD in order to compare the effects of iron toxicity in these two diseases. We compared the prevalence of LV dysfunction and its relationship to iron-toxicity in THAL, txSCD and control SCD.
METHODS AND RESULTS: Baseline or year 1 echocardiograms (ECHOs) were available in 45% of the patients (80 THAL, 94 txSCD and 16 SCD controls) and reviewed for evidence of LV dysfunction, defined as an ejection fraction ≤ 55% or shortening fraction ≤ 28%. Pulmonary hypertension (PHT) was defined as a tricuspid regurgitant jet velocity (TRV) ≥ 2.5 m/s or pulmonary artery pressure (PAP) ≥ 35 mmHg. ECHOs reported as normal, even without TRV or PAP recorded, were assumed to be negative for PHT. At study entry, THAL and txSCD patients were severely iron over-loaded and their average ferritin and liver iron concentrations were not significantly different: 3506 g/dl and 20 mg/g dry weight. (Serum ferritin in the control SCD was 120 g/dl.) The average age of the patients was 30.3 ± 12 yrs, and did not differ across the three groups. LV dysfunction was found in 22% THAL; THAL patients with LV dysfunction had been transfused longer than those with normal ECHOs (26.5 vs. 21.1 yrs, p=. 03). A subgroup of THAL was screened with cardiac MRI: 11/21 (52%) had evidence of cardiac iron deposition, 4 of these patients (36%) had LV dysfunction. In THAL screened with MRI, all patients with LV dysfunction had cardiac iron deposition. LV dysfunction was seen in 14% of txSCD but in 0% of the control SCD. txSCD patients with LV dysfunction were older (43.7 vs. 28.5, p <. 0001) and more likely to have PHT (75% vs. 22%, p < .001). PHT was more common in txSCD than THAL (29% vs. 15%, p=. 03) and found in 13% of the control SCD group. No txSCD patients were screened with MRI.
CONCLUSIONS: LV dysfunction is common in transfusion dependent THAL and associated with duration of transfusion and iron deposition. In SCD, patients with cardiomyopathy were chronically transfused, older, and more likely to have PHT. SCD patients are developing iron overload similar to THAL; cardiac MRI studies are essential for the evaluation of iron deposition and its relationship to cardiomyopathy.