Myocardial fibrosis: a concerning finding without an etiology. (A) Despite the “simple” point mutation and hemoglobin S formation that underlies SCD, there are numerous adverse cellular and biochemical changes. Hemoglobin S polymerization leads to decreased erythrocyte deformability and eventually microvascular occlusion and intravascular hemolysis. Both microcirculatory occlusion and intravascular hemolysis act in concert to cause tissue ischemia-reperfusion injury, chronic inflammation, and decreased NO bioavailability. We do not know which abnormality, if any, leads to myocardial fibrosis. (B) ECV quantification in SCD is exceeded only by ECV quantification at the site of infarcted myocardium. CMP, cardiomyopathy; SCA, sickle cell anemia; TM, thalassemia major (+iron, indicates presence of myocardial iron overload). See Figure 2C in the article by Niss et al that begins on page 205.