How chronic intravascular hemolysis leads to precapillary pulmonary arterial hypertension (PAH) and pulmonary arteriole vaso-constriction and smooth muscle hypertrophy, and how chronic anemia leads to diastolic left heart disease (now also called HFpEF). These 2 disease manifestations are diagnosed by using Doppler echocardiography and right heart catheterization. PVR, pulmonary vascular resistance; RA, right atrium; RV, right ventricle. Reprinted from The Lancet, 387, Gladwin MT, Cardiovascular complications and risk of death in sickle cell disease, 2565-2574, 2016, with permission from Elsevier.