1. Date of download: 6/22/2016 Copyright © The American College of Cardiology. All rights reserved. From: Cardiovascular Abnormalities in Sickle Cell Disease J Am Coll Cardiol. 2012;59(13):1123-1133. doi:10.1016/j.jacc.2011.10.900 Mechanisms of Hemolytic Anemia in Reducing NO Bioavailability and Association With Vasculopathic Sub-Phenotypes of SCD Hemolysis releases cell-free plasma hemoglobin (Hb) and arginase 1 into plasma, which catabolize nitric oxide (NO) and L-arginine. Activation of vascular oxidases—such as xanthine oxidase (XO), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and uncoupled endothelial nitric oxide synthase (eNOS)—generate superoxide, which scavenges NO. Hemolytic anemia and reduced NO bioavailability are associated with vasculopathic clinical complications in sickle cell disease (SCD) patients. LDH = lactate dehydrogenase; metHb = methemoglobin; NO 3 − = nitrate; O 2 = oxygen; ONOO = peroxynitrite. Figure Legend:

2. Date of download: 6/22/2016 Copyright © The American College of Cardiology. All rights reserved. From: Cardiovascular Abnormalities in Sickle Cell Disease J Am Coll Cardiol. 2012;59(13):1123-1133. doi:10.1016/j.jacc.2011.10.900 Mechanisms of PH in SCD Patients A pulmonary vessel with severe intimal and smooth muscle proliferation is shown from a 35-year-old patient with sickle cell disease (SCD) who died suddenly with known pulmonary arterial hypertension. Mechanisms that contribute to the development of pulmonary hypertension (PH) identified in animal and human studies are summarized. ADMA = asymmetric dimethylarginine; ET = endothelin; NADPH = nicotinamide adenine dinucleotide phosphate; NOS = nitric oxide synthase; ROS = reactive oxygen species; TGF = transforming growth factor. Figure Legend:

3. Date of download: 6/22/2016 Copyright © The American College of Cardiology. All rights reserved. From: Cardiovascular Abnormalities in Sickle Cell Disease J Am Coll Cardiol. 2012;59(13):1123-1133. doi:10.1016/j.jacc.2011.10.900 Sensitivity and Specificity Analysis of Diastolic Dysfunction Measures in SCD Patients Receiver operating characteristic (ROC) curve for tissue Doppler lateral E/e' ratio to predict a pulmonary capillary wedge pressure >15 mm Hg by cardiac catheterization within 72 h in sickle cell disease patients. AUC = area under the curve. Figure Legend:

4. Date of download: 6/22/2016 Copyright © The American College of Cardiology. All rights reserved. From: Cardiovascular Abnormalities in Sickle Cell Disease J Am Coll Cardiol. 2012;59(13):1123-1133. doi:10.1016/j.jacc.2011.10.900 Echocardiographic Image From a Sickle Cell Disease Patient This echocardiographic image (apical 4-chamber view) from a sickle cell disease patient admitted with acute chest syndrome shows a dilated, dysfunctional right ventricle. Please see the Online Video for the echocardiogram of this patient. Figure Legend: