The natural course and outcomes of PAH in patients with ACHD with Eisenmenger syndrome, as contrasted to other adults with PAH, remain incompletely defined. However, it is believed that better survival and func- tional ability of untreated adults with Eisenmenger syn- drome might be explained by sharing of loading condi- tions between right- and left-sided cardiac chambers, as well as multiorgan system adaptations that develop over time. The fundamental cause of Eisenmenger syndrome is elevated pulmonary vascular resistance driving right- to-left intracardiac or great arterial shunting leading to systemic arterial desaturation. The risk of development of Eisenmenger syndrome is influenced by concomitant congenital syndromes, anatomic location of congenital defects, size of anatomic defects, genetic factors, and environmental exposures. Pathophysiological mechanisms contributing to de- velopment of Eisenmenger syndrome are not fully un- derstood. Suggested triggers and pathways include blood flow-induced shear and circumferential stress, vasoconstriction, and vascular cell proliferation associ- ated with fibrosis and thrombosis. Cyanosis, erythrocytosis, abnormalities of loading conditions, and abnormalities of systemic and pulmo- nary perfusion all contribute to functional incapacity and potential for multiorgan system dysfunction and other sequelae, including stroke, brain abscess, osteo- Recommendations for Eisenmenger Syndrome (Continued) COR LOE Recommendations CLINICAL STATEMENTS AND GUIDELINES arthropathy, iron deficiency, reduced glomerular clear- ance and susceptibility to acute renal insufficiency, ne- phrosis, pulmonary arterial thrombosis and dissection, hemoptysis, pulmonary parenchymal infections, dias- tolic and systolic cardiac dysfunction, arrhythmia, HF, and SCD. Palliative therapies that may be helpful include sup- plemental oxygen if systemic arterial oxygen saturation is empirically noted to rise in response, systemic antico- agulation, and avoidance of circumstances recognized to contribute to risk (eg, high altitude, pregnancy, ex- posure to high heat or humidity leading to vasodilation, nephrotoxin exposure, extreme exertion, large shifts in intravascular volume). However, supportive data for these strategies are limited or nonexistent. 