The Changing Landscape of Pulmonary Arterial Hypertension in the Adult with Congenital Heart Disease

Figure 1. Changing subgroup distribution of pulmonary arterial hypertension in adult congenital heart disease: patients on treatment at two congenital heart disease (CHD) designated centers in the Netherlands from 2005 to 2015. PAH: pulmonary arterial hypertension.

Figure 2. Transthoracic echocardiographic (apical four chamber view) images of the 4 clinical subgroups in pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD): (A) Eisenmenger syndrome: atrioventricular septal defect; (B) PAH associated with prevalent systemic-to-pulmonary shunt lesion: atrial septal defect with left-to-right shunt; (C) PAH associated with small or coincidental cardiac defect: secundum atrial septal defect; (D) PAH after defect closure: closed atrial septal defect. LA = left atrium; LV = left ventricle; RA = right atrium; RV = right ventricle.

Figure 3. Involvement of the endothelin, nitric oxide (NO) and prostacyclin pathways in the pathogenesis of pulmonary arterial hypertension. (Left) In the endothelin pathway the effects of endothelin (ET)-1 are mediated via the ETA and ETB receptors in the smooth muscle cells. Receptor binding leads to mobilization of Ca2+ resulting in vasoconstriction and proliferation. Selective and dual endothelin receptor antagonists (ERAs) inhibit this pathway; (Middle) The nitric oxide pathway involves the production of cyclic guanosine monophosphate (cGMP), which leads to inhibition of Ca2+ entry, resulting in vasodilation and antiproliferation. Soluble guanylate cyclase (sGC) stimulators and phosphodiesterase type 5 inhibitors (PDE-5i) activate this pathway; (Right) In the prostacyclin (PGI2) pathway, prostanoid receptors IP, EP3, and TP regulate vessel tone (other prostanoid target receptors are not functionally expressed in the pulmonary artery). Selective non-prostanoid IP receptor agonists and PGI2 analogues bind to the IP receptor, which induces adenylate cyclase activity, cyclic adenosine monophosphate (cAMP) production, resulting in decreased Ca2+ and leads to vasodilation and…