Patients with atrial septal defect (ASD) initially present with a left-to-right shunt, which may cause elevated pulmonary artery pressures at rest and/or during exercise. However, this persistently elevated pulmonary blood-flow also causes progressive lesions of the pulmonary vasculature, as first described by Heath and Edwards. The earlier stages present with medial hypertrophy and/or intimal proliferation and are largely reversible after closure of the defect. Later stages, however, are irriversible: the origin of pulmonary arterial hypertension (PAH). Eventually, this volume and pressure overload of the right heart may lead to heart failure and/or arrhythmias. As PVR exceeds systemic resistance, the shunt is reversed (right-to-left shunt) leading to systemic arterial desaturation (and the related consequences: polyglobulia, hyperuricemia, decreased renal function and abnormal coagulation): the Eisenmenger syndrome (ES). When occlusive fibrotic lesions have developed later in life, closure of the ASD, although still feasible, may not result in complete normalization of pulmonary artery pressures. Moreover, it has been shown that closure after the age of 40 years is associated with worse outcome. It has been suggested that an abnormal increase in pulmonary artery pressures during exercise reflects mild pulmonary vascular disease. However, pulmonary artery pressures are defined by both cardiac output and pulmonary vascular resistance. During exercise, the relationship between pulmonary artery pressures and cardiac output is slightly curvilinear because of a natural distensibility of the pulmonary arterioles. Using bicycle stress echocardiography, pulmonary vascular resistance can be estimated either as a ratio of pulmonary artery pressure and cardiac output at each stage (total PVR) or by using linear regression analysis of the pressure-flow plots (dynamic PVR).