Association between diffuse myocardial fibrosis and diastolic dysfunction in sickle cell anemia.

Omar Niss, Robert Fleck, Fowe Makue, Tarek Alsaied, Payal Desai, Jeffrey A. Towbin, Punam Malik, Michael D. Taylor and Charles T. Quinn

Key points

  • Diffuse myocardial fibrosis is a common and novel mechanism of heart disease in SCA that can be detected non-invasively.

  • Diffuse myocardial fibrosis is strongly associated with diastolic dysfunction in individuals with SCA.


Sickle cell anemia (SCA)-related cardiomyopathy is characterized by diastolic dysfunction and hyperdynamic features. Diastolic dysfunction portends early mortality in SCA. Diastolic dysfunction is associated with microscopic myocardial fibrosis in SCA mice, but the cause of diastolic dysfunction in humans with SCA is unknown. We used cardiac magnetic resonance (CMR) measurements of extracellular volume fraction (ECV) to discover and quantify diffuse myocardial fibrosis in 25 individuals with SCA (mean age 23±13 years), and determine the association between diffuse myocardial fibrosis and diastolic dysfunction. ECV was calculated from pre- and post-gadolinium T1-measurements of blood and myocardium, and diastolic function was assessed by echocardiography. ECV was markedly increased in all participants compared to controls (0.44±0.08 vs. 0.26±0.02, P<0.0001) indicating the presence of diffuse myocardial fibrosis. Seventeen (71%) had diastolic abnormalities and 7 (29%) met the definition of diastolic dysfunction. Participants with diastolic dysfunction had higher ECV (0.49±0.07 vs. 0.37±0.04, P=0.01) and NT-proBNP (191±261 vs. 33±33 pg/mL, P=0.04) but lower hemoglobin (8.4±0.3 vs.10.9±1.4 g/dL, P=0.004) compared to participants with normal diastolic function. Participants with the highest ECV values (≥0.40) were more likely to have diastolic dysfunction (P=0.003) and increased left atrial volume (57±11 vs. 46±12 mL/m2, P=0.04) compared to those with ECV<0.4. ECV correlated with hemoglobin (r=-0.46, P=0.03) and NT-proBNP (r=0.62, P=0.001). In conclusion, diffuse myocardial fibrosis, determined by ECV, is a common and previously underappreciated feature of SCA that is associated with diastolic dysfunction, anemia, and high NT-proBNP. Diffuse myocardial fibrosis is a novel mechanism that appears to underlie diastolic dysfunction in SCA.

  • Submitted February 8, 2017.
  • Accepted May 11, 2017.