Modulation of pulmonary vascular resistance as a target for therapeutic interventions in Fontan patients: focus on phosphodiesterase inhibitors.

Despite advancements in surgical techniques over the past 20 years, Fontan patients have decreased exercise capacity as a consequence of an inherent inability to adequately increase cardiac output during exercise. They are also affected by several complications that are associated with considerable morbidity and mortality. As the systemic and pulmonary circulations are placed in series without a subpulmonary ventricle propelling blood through the pulmonary vasculature, the systemic venous pressure and the respiratory mechanics are the only forces driving pulmonary blood flow. In Fontan circulation, pulmonary vascular resistance is the single most important factor involved in the limitation of cardiac output and treatments able to decrease pulmonary vascular resistance might conversely improve cardiac output and exercise capacity. In this article we discuss the initial experience with the use of sildenafil in Fontan patients and we discuss the possible mechanisms through which sildenafil might positively act in Fontan circulation.