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

Abstract

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 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 with controls (0.44 ± 0.08 vs 0.26 ± 0.02, < .0001), indicating the presence of diffuse myocardial fibrosis. Seventeen patients (71%) had diastolic abnormalities, and 7 patients (29%) met the definition of diastolic dysfunction. Participants with diastolic dysfunction had higher ECV (0.49 ± 0.07 vs 0.37 ± 0.04, = .01) and N-terminal pro-brain natriuretic peptide (NT-proBNP; 191 ± 261 vs 33 ± 33 pg/mL, = .04) but lower hemoglobin (8.4 ± 0.3 vs 10.9 ± 1.4 g/dL, = .004) compared with participants with normal diastolic function. Participants with the highest ECV values (≥0.40) were more likely to have diastolic dysfunction ( = .003) and increased left atrial volume (57 ± 11 vs 46 ± 12 mL/m, = .04) compared with those with ECV<0.4. ECV correlated with hemoglobin ( = -0.46, = .03) and NT-proBNP ( = 0.62, = .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.

Diastolic dysfunction is associated with exercise impairment in patients with sickle cell anemia

“…The association between diffuse myocardial fibrosis and DD has been demonstrated in our previous studies . All participants in this study had abnormally elevated ECV, indicating diffuse myocardial fibrosis .…”

“…Patients with DD had numerically higher native T1 and ECV values compared to patients without DD (Table ). ECV was elevated in all patients 0.43 ± 0.08 compared to our institutional normal control values 0.26 ± 0.02, P < 0.001 . Although all participants had abnormally elevated ECV, there was no association between ECV and either %predicted VO 2 or VE/VCO 2 slope (Table ).…”

“…CMR was performed on a 1.5 T scanner (Philips Ingenia, Best, The Netherlands). ECV was measured from T1 maps acquired with a modified look‐locker inversion recovery (MOLLI) sequence in the short and long axis planes before and 10 min post contrast as previously described . All planimetric and T1 analyses were done with CMR42 (Circle Imaging, Alberta, Canada).…”

“…Tissue Doppler imaging was used to determine mitral and tricuspid valve annular velocities in early (e′) and late diastole (a′) at both the septal and lateral annulus. Continuous‐wave Doppler sampling of the peak tricuspid regurgitation velocity (TRV) was used …”

Myocardial fibrosis: the heart of diastole?

“…1 S CD is a model for chronic and diffuse vasculopathy resulting in tissue infarction and ischemia-reperfusion injury. 2,3 Much attention has been placed on diffuse endothelial disease in SCD.…”