Pulmonary vascular disease in Fontan circulation-is there a rationale for pulmonary vasodilator therapies?

The Fontan circulation is a palliative concept for patients with univentricular hearts. The central veins are connected directly to the pulmonary arteries (cavo-pulmonary connection) to separate the pulmonary and the systemic circulation. There is no sub-pulmonary ventricle that generates pressure to drive blood through the pulmonary arteries. Pulmonary blood flow is determined by central venous pressure (CVP) and pulmonary vascular resistance (PVR). The capability of the Fontan circulation to compensate for alterations in PVR is limited, as CVP can only be increased within narrow ranges without adverse clinical consequences. Consequently, systemic ventricular preload and cardiac output are dependent on a healthy lung with low PVR. Failure of the Fontan circulation is relatively common. In addition to ventricular dysfunction, maladaptive pulmonary vascular remodeling resulting in increased pulmonary resistance may play a key role. The pathophysiology of the maladaptive vascular processes remains largely unclear and diagnosis of an increased PVR is challenging in Fontan circulation as accurate measurement of pulmonary arterial blood flow is difficult. In the absence of a sub-pulmonary ventricle, pulmonary artery pressure will almost never reach the threshold conventionally used to define pulmonary arterial hypertension. There is a need for markers of pulmonary vascular disease complementary to invasive hemodynamic data in Fontan patients. In order to treat or prevent failure of the Fontan circulation, pathophysiological considerations support the use of pulmonary vasodilators to augment pulmonary blood flow and systemic ventricular preload and lower CVP. However, to date the available trial data have neither yielded enough evidence to support routine use of pulmonary vasodilators in every Fontan patient nor have they been helpful in defining subgroups of patients that might benefit from such therapies. This review discusses potential pathomechanisms of pulmonary vascular disease; it summarizes the current knowledge of the effects and efficacy of pulmonary vasodilator therapy in Fontan patients and tries to outline areas of potential future research on the diagnosis and treatment of pulmonary vascular disease and Fontan failure.