Phenotypes in pulmonary arterial hypertension: impact on outcomes

This thesis explores the outcomes of three distinct forms of pulmonary arterial hypertension (PAH). Idiopathic pulmonary arterial hypertension (IPAH) the rarest form, systemic sclerosis (SSc) associated pulmonary arterial hypertension and finally adult congenital heart disease (CHD) associated pulmonary arterial hypertension. Despite the advancements in available therapies in the last decade for PAH, the disease course continues to be devastating, with the only cure being cardiopulmonary/pulmonary transplantation. This alternative format thesis, of seven main chapters, explores potentially overlooked features which may confer a poorer prognosis in this group of PAH patients. The overall objective is to establish the importance of accurate phenotyping of the PAH patient to assist in improving overall morbidity and mortality of this group. This work corroborates the well-established poor prognostic indicators, such as male gender in IPAH and the sub-group of SSc-PAH in comparison to IPAH with previous large studies. A more novel finding, is the deleterious effect of features in keeping with left heart and lung disease in patients with IPAH and SSc-PAH. As well as the clinical presence of a left to right defect e.g., Atrial septal defect, in those with CHD-PAH. Another established predictor of poor outcome in IPAH and SSc-PAH, is a reduced diffusing capacity of the lung for carbon monoxide (DLco), work within this thesis explores this finding and suggests that the mechanistic pathway of a reduced DLco in IPAH and SSc-PAH is likely to differ. The main conclusion therefore, of this thesis, is in order to offer the best management to our group of PAH patients, the correct clinical phenotyping is essential to accurately assess risk of mortality. This allows either a change to a patient’s outcome with judicious use of pulmonary vasodilator therapies or if this is not a suitable option for a patient, it allows the clinical team to have an early open an honest discussion about their prognosis so that our PAH patient can be fully informed and prepared.