Mechanistic insights and characterization of sickle cell disease-associated cardiomyopathy

Background-Cardiovascular disease is an important cause of morbidity and mortality in sickle cell disease (SCD). We sought to characterize sickle cell cardiomyopathy using multimodality noninvasive cardiovascular testing and identify potential causative mechanisms. Methods and Results-Stable adults with SCD (n=38) and healthy controls (n=13) prospectively underwent same day multiparametric cardiovascular magnetic resonance (cine, T2* iron, vasodilator frst pass myocardial perfusion, and late gadolinium enhancement imaging), transthoracic echocardiography, and applanation tonometry. Compared with controls, patients with SCD had severe dilation of the left ventricle (124±27 vs 79±12 mL/m²), right ventricle (127±28 vs 83±14 mL/m²), left atrium (65±16 vs 41±9 mL/m²), and right atrium (78±17 vs 56±17 mL/m ²; P<0.01 for all). Patients with SCD also had a 21% lower myocardial perfusion reserve index than control subjects (1.47±0.34 vs 1.87±0.37; P=0.034). A signifcant subset of patients with SCD (25%) had evidence of late gadolinium enhancement, whereas only 1 patient had evidence of myocardial iron overload. Diastolic dysfunction was present in 26% of patients with SCD compared with 8% in controls. Estimated flling pressures (E/e′, 9.3±2.7 vs 7.3±2.0; P=0.0288) were higher in patients with SCD. Left ventricular dilation and the presence of late gadolinium enhancement were inversely correlated to hepatic T2* times (ie, hepatic iron overload because of frequent blood transfusions; P<0.05 for both), whereas diastolic dysfunction and increased flling pressures were correlated to aortic stiffness (augmentation pressure and index, P<0.05 for all). Conclusions-Sickle cell cardiomyopathy is characterized by 4-chamber dilation and in some patients myocardial fbrosis, abnormal perfusion reserve, diastolic dysfunction, and only rarely myocardial iron overload. Left ventricular dilation and myocardial fbrosis are associated with increased blood transfusion requirements, whereas left ventricular diastolic dysfunction is predominantly correlated with increased aortic stiffness.