Non medical treatment

Balloon atrial septostomy 
The presence of a right-left shunt, secondary to congenital cardiac malformation, or a patent foramen oval, among patients with severe PAH, seems to carry a better prognosis [270]. Atrioseptostomy is an artificial communication interauricular to decrease the right heart volume, subjected to a high after load secondary to increased pulmonary resistances [271]. The surgical creation of a right-left shunt decreases right auricular pressure and increases systemic blood flow, later on, reduction in right ventricular wall tension is expected [271]. Thus, in spite of arterial desaturation induced by the shunt, oxygen delivery is improved [271]. Atrioseptostomy has however never been studied in controlled clinical trials. However, several experienced teams reported their data and it seems that immediate mortality is high, reaching 14% during the first week, particularly in the case of severe desaturation and right heart failure [105,271-273]. Among patients who survived, clinical improvement with regression of symptoms and gain of functional capacity can be observed. Atrioseptostomy should only be carried out in centers with significant experience, both in performance of atrioseptostomy and management of PAH patients, especially post interventional. The impact of balloon atrial septostomy on long term survival has not been established in RCTs [271,274].

Lung transplantation 
Lung transplantation was historically the treatment of choice for severe PAH and remains treatment of choice if medical treatments are insufficient [197]. However, this particularly heavy surgery can be proposed only to a minority of patients suffering from PAH. Moreover, long-term benefits remain disappointing with approximately 50% survival at 5 years [275]. Early mortality is mainly related to infectious complications whereas late mortality reflects mostly chronic rejection such as obliterating bronchiolitis. Mono-pulmonary transplantation had good long-term results [276,277], but most centers currently prefer bi-pulmonary transplantation which has less post-operative complications [278]. Cardiopulmonary transplantation may be necessary for patients presenting with terminal right heart failure or complex congenital heart disease [279]. In conclusion, PAh is a rare group of diseases that shares broadly similar pathological features, pathophysiology and clincal presentation. The discovery of the central role of endothelial dysfunction leads to the development of specific PAH therapies including prostanoids, endothelin receptor antagonists and PDE-5 inhibitors. Even these therapeutic advances, no cure of the disease can be achieved and the prognosis remains unsatisfactory.