Reversal of a rheologic cardiomyopathy following hematopoietic stem cell transplantation for sickle cell disease

Abstract

Cardiac complications have been well-described in sickle cell disease; however, it has been rare to see improvements in cardiac abnormalities following any interventions. Previous work has shown no significant structural changes after treatment with hydroxyurea. The cardiac effects of red blood cell exchange transfusion (RBCx) and hematopoietic stem cell transplantation (HSCT) have not been well described. We studied 56 patients undergoing HSCT (41 HLA-matched, 15 haploidentical), of whom 32 had RBCx within 3 months before HSCT. Echocardiograms and laboratory parameters were obtained at baseline, and at 3, 6, and 12 months following HSCT. Although hemolytic parameters and anemia improved following RBCx, there was a small increase in left ventricular volume index. Following successful HSCT, however, there were significant improvements in cardiac size, function, and diastolic filling parameters at 3 months followed by continued smaller improvements up to 1 year. There was a significant improvement in N-terminal pro B-type natriuretic peptide levels and a trend toward improvement in 6-minute walk time 1 year after HSCT. The magnitude of cardiac improvement seen following HSCT was comparable to that observed following correction of a volume overload state as seen in pregnancy or after repair of chronic valvular regurgitation. Further studies in sickle cell disease patients will help delineate which cardiac complications and what level of severity should be considered indications for HSCT.

Graphical abstract

Figure 1.

LVEDV/BSA decreased significantly across all follow-up time points when each was independently compared with baseline (3 months, P ≤ .005; 6 months, P ≤ .005; 1 year, P ≤ .005). However, the degree of change between the 3- to 6-month and 6- to 12-month follow-up time points was not found to be significant.

Figure 2.

There was a significant negative correlation between LVEDV/BSA and hemoglobin (Spearman r = −0.55, P = .0002) from baseline to the 3 months’ follow-up.

Figure 3.

In patients with a TR velocity ≥2.5 m/s at baseline, there was a significant decrease in TR velocity at only the 1-year follow-up time point (1 year, P ≤ .005).

Figure 4.

Hemoglobin levels improved significantly in successful HSCT patients at 3 months with continued smaller improvements at 6 and 12 months. In unsuccessful HSCT patients, there were no significant changes in hemoglobin levels.