Assessment of Cardiac Abnormalities in Sickle Cell Disease Patients Using Cardiac Magnetic Resonance Imaging (CMR)
Authors: Morin Cara , Sharma Akshay , Beasley Gary , Hankins Jane S , High Stacy , Kennedy Amanda , Lovins Richard , Rai Parul , Triplett Brandon M , Johnson Jason 
Published: November 2021

Abstract
Introduction
Sickle cell disease (SCD) is characterized by chronic hemolytic anemia which predisposes patients to high output heart failure. Recently it has been recognized that repetitive microvascular ischemic insults and reperfusion injury result in diffuse myocardial fibrosis and cardiac remodeling that eventually leads to irreparable myocardial injury. Superimposed on these cardiac insults, patients with SCD often have iron overload related to chronic transfusions. Together, these insults produce a unique SCD-related cardiomyopathy characterized by restrictive physiology with LV dilation. Cardiac Magnetic Resonance Imaging (CMR) is the only non-invasive technique for assessing and quantifying diffuse myocardial fibrosis with simultaneous highly accurate assessment of heart size and systolic and diastolic function. Diffuse myocardial fibrosis is measured by a CMR technique called T1 mapping and calculated as extracellular volume (ECV), which may serve as an early marker of sickle cell related cardiomyopathy. An early marker for SCD-related cardiomyopathy would allow for efficient screening, prevention, and institution of treatment strategies. We describe utilization of CMR to evaluate cardiac pathology in a cohort of pediatric SCD patients.
Methods
Twenty-six children with SCD underwent CMR, as clinically indicated, between January 2020 and July 2021 at our institution. We analyzed cardiac chamber size (left atrium [LA], left ventricle [LV], right ventricle [RV]), systolic and diastolic function parameters, and quantitative myocardial parametric mapping values (T1 pre- and post-contrast and T2*) for these patients. ECV was calculated for all patients using T1 pre- and post-contrast values in conjunction with current hemoglobin values. Four patients underwent an allogeneic hematopoietic cell transplant (HCT) for SCD and had serial CMR performed before and 1 month after HCT.
Results
Median age of patients was 17 years; 12 (70%) were female; 22 (84%) had HbSS, 3 (12%) had HbSC and 1 (4%) had Hb S beta thalassemia. 15 (58%) patients had LA enlargement and only a few had ventricular enlargement (LV, 11 [42%]; RV, 9 [35%]). Patients rarely had had LV (4 [15%]) or RV (1 [4%]) systolic dysfunction. Twenty-five (96%) patients had increased ECV; median 30.5% (IQR 28-34%, reference normal 20.8% +/- 2.4). All patients had normal myocardial T2* values indicating no myocardial iron deposition. Additional details are provided in Table. Among those who underwent HCT, all 4 had elevated ECV at baseline, which improved in 1 patient 1-month post-HCT (27% [pre] to 21% [post]). One patient had a dilated LA at baseline with the other 3 developing LA dilation at 1-month post HCT.
Conclusion
CMR provides accurate and reproducible measurements of chamber sizes/ventricular volumes, myocardial mass, and ventricular function. Multiparametric mapping enabled quantitative evaluation of myocardial fibrosis in patients with SCD. We found that diffuse myocardial fibrosis is often present in children with SCD, even those with apparently normal cardiac function.
This indicates damage to the myocardium occurs before symptoms or measurable changes on echocardiography, calling into question our current screening procedures. T1 mapping to monitor the progression of fibrosis could help evaluate response to current therapies including SCD directed therapies, cardioprotective medications, and curative options such as HCT and gene therapy. Hence, we believe that cardiac MRI is complementary to echocardiography and provides additional clinically relevant information that will help guide treatment in patients with SCD.
Additionally, it has been shown that patients with SCD who undergo successful HCT exhibit significant improvements in cardiac size, function, and diastolic filling parameters as early as 3 months after the procedure, with improvements continuing slowly up to 1 year after HCT. Early post-HCT evaluation in our cohort did show moderate improvement in ECV in one HCT recipient. Further follow up with serial monitoring is ongoing to evaluate long term changes in these patients. Data on additional patients who have undergone serial CMR monitoring after HCT will be presented at the ASH annual meeting.
Figure 1 Figure 1.

Disclosures
Sharma: CRISPR Therapeutics: Other, Research Funding; Medexus Inc: Consultancy; Spotlight Therapeutics: Consultancy; Novartis: Other: Salary support paid to institution; Vertex Pharmaceuticals/CRISPR Therapeutics: Other: Salary support paid to institution; Vindico Medical Education: Honoraria. Hankins: UpToDate: Consultancy; Global Blood Therapeutics: Consultancy; Vindico Medical Education: Consultancy; Bluebird Bio: Consultancy. Triplett: Miltenyi: Other: Travel, meeting registration.