Improvement in Cardiac Morphology Demonstrated by Cardiac Magnetic Resonance Imaging and Echocardiography after Haploidentical Hematopoietic Cell Transplantation in Adults with Sickle Cell Disease.

Cardiopulmonary complications account for approximately 40% of deaths in patients with sickle cell disease (SCD). Diffuse myocardial fibrosis, elevated tricuspid regurgitant jet velocity (TRV) and iron overload are all associated with early mortality. Although HLA-matched sibling hematopoietic cell transplantation (HCT) offers a potential cure, less than 20% of patients have a suitable donor. Haploidentical HCT allows for an increased donor pool and has recently demonstrated improved safety and efficacy. Our group has reported improved cardiac morphology via echocardiography at 1 year after HCT. Here we describe the first use of cardiac magnetic resonance imaging (CMR), the gold standard for measuring volume, mass, and ventricular function, to evaluate changes in cardiac morphology post-HCT in adults with SCD. We analyzed baseline and 1-year data from 12 adults with SCD who underwent nonmyeloablative haploidentical peripheral blood HCT at the National Institutes of Health. Patients underwent noncontrast CMR at 3 T, echocardiography, and laboratory studies. At 1 year after HCT, patients showed marked improvement in cardiac chamber morphology by CMR, including left ventricular (LV) mass (70.2 to 60.1 g/m2; P = .02) and volume (114.5 to 90.6 mL/m2; P = .001). Furthermore, mean TRV normalized by 1 year, suggesting that HCT may offer a survival benefit. Fewer patients had pathologically prolonged native myocardial T1 times, an indirect marker of myocardial fibrosis at 1 year; these data showed a trend toward significance. In this small sample, CMR was very sensitive in detecting cardiac mass and volume changes after HCT and provided complementary information to echocardiography. Notably, post-HCT improvement in cardiac parameters can be attributed only in part to the resolution of anemia; further studies are needed to determine the roles of myocardial fibrosis reversal, improved blood flow, and survival impact after HCT for SCD.

Severe cardiac iron toxicity in two adults with sickle cell disease.

BACKGROUND: Use of chronic blood transfusions as a treatment modality in patients with blood disorders places them at risk for iron overload. Since patients with ß-thalassemia major (TM) are transfusion-dependent, most studies on iron overload and chelation have been conducted in this population. While available data suggest that compared to TM, patients with sickle cell disease (SCD) have a lower risk of extrahepatic iron overload, significant iron overload can develop. Further, previous studies have demonstrated a direct relationship between iron overload and morbidity and mortality rates in SCD. However, reports describing the outcome for patients with SCD and cardiac iron overload are rare. STUDY DESIGN AND METHODS: We performed a retrospective analysis and identified two SCD patients with cardiac iron overload. We provide detailed descriptions of both cases and their outcomes. RESULTS: Serum ferritin levels ranged between 17,000 and 19,000 µg/L. Both had liver iron concentrations in excess of 35 mg of iron per gram of dried tissue as well as evidence of cardiac iron deposition on magnetic resonance imaging. One patient died of an arrhythmia and had evidence of severe multiorgan iron overload via autopsy. On the other hand, after appropriate therapy, a second patient had improvement in cardiac function. CONCLUSION: Improper treatment of iron overload in SCD can lead to a fatal outcome. Alternatively, iron overload may potentially be prevented or reversed with judicious use of blood transfusions and early use of chelation therapy, respectively.