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

Abstract

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. While HLA-matched sibling hematopoietic cell transplant (HCT) offers a potential cure, fewer 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 one year after HCT. Herein, 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 received nonmyeloablative haploidentical peripheral blood HCT at the NIH. Patients underwent non-contrast CMR at 3T, echocardiography, and laboratory studies. One year after HCT, patients showed marked improvement in cardiac chamber morphology by CMR, including left ventricular (LV) mass and volume (70.2 to 60.1 g/m2, p = 0.02; 114.5 to 90.6 mL/m2, p = 0.001). 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 required to determine the role of myocardial fibrosis reversal, improved blood flow, and survival impact after HCT for SCD.