Targeted Therapies in Patients with Pulmonary Arterial Hypertension Due to Congenital Heart Disease

Pulmonary arterial hypertension (PAH) is a devastating cardiovascular disease leading to right heart failure and death if untreated. Medical therapies for PAH have evolved substantially over the last decades and are associated with improvements in functional class, quality of life, and survival. PAH-targeted therapies now consist of multiple inhaled, oral, subcutaneous, and intravenous therapies targeting the phosphodiesterase, guanylate cyclase, endothelin and prostacyclin pathways. Patients with congenital heart disease (CHD) are at high risk of developing PAH and growing evidence exists that PAH-targeted therapy can be beneficial in PAH-CHD. However, the PAH-CHD patient population is challenging to treat due to the heterogeneity and complexity of their cardiac lesions and associated comorbidities. Furthermore, most high-quality randomized placebo-controlled trials investigating the effects of PAH-targeted therapies only included a minority of PAH-CHD patients. Few randomized, controlled trials have investigated the effects of PAH-targeted therapy in pre-specified PAH-CHD populations. Consequently, the results of these clinical trials cannot be extrapolated broadly to the PAH-CHD population. This review summarizes the data from high-quality clinical PAH treatment trials with a specific focus on the PAH-CHD population.