The clinical spectrum and natural history of pulmonary hypertension in the modern treatment era

Pulmonary hypertension (PH) is a heterogeneous condition with classification based on shared pathophysiological characteristics. There is a paucity of literature reflecting the spectrum of disease across the 5 diagnostic groups encountered at a specialist referral centre in the era of the widespread availability of targeted pulmonary vascular therapy.

The first part of this thesis focuses on the ASPIRE registry; a large registry of contemporary, consecutive, treatment-naïve patients identified at a specialist PH centre using a catheter-based approach. Uniquely, the ASPIRE registry compares the natural history of all forms of PH, providing new and novel insights into the natural history of rare groups such as pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension and more common but less well studied forms such as PH associated with left heart disease and lung disease where the role of targeted therapies is not clear. This registry demonstrates that outcomes and characteristics differ between and within PH diagnostic groups. In addition, the current system of diagnostic classification in PH has prognostic value even when adjusted for age and haemodynamic severity emphasizing the importance of systematic evaluation and precise classification.

The second part of this thesis focuses on patients in group 3; pulmonary hypertension associated with lung disease, concentrating particularly on chronic obstructive pulmonary disease (COPD) and emphysema, the most common type of lung disease associated with PH. The characteristics of patients with severe PH associated with COPD (PH-COPD) differed from those with mild to moderate PH-COPD despite similar degrees of emphysema on CT scan. Survival in PH-COPD was poor and this study identified independent predictors of outcome. Patients with severe PH-COPD share certain characteristics with PAH such as the degree of haemodynamic severity and right ventricular impairment. This leads to the question of whether therapies frequently prescribed in PAH should be considered for this group. In the largest cohort yet studied, a minority of patients with severe PH-COPD demonstrated objective evidence of improvement with compassionate treatment with targeted pulmonary vascular therapies and where there was evidence of clinical benefit, patients demonstrated superior survival. This data suggests that further evaluation of targeted therapies is warranted in patients with severe PH-COPD.

In conclusion, retrospective review of this cohort of patients has provided a detailed comparison of characteristics between and within PH diagnostic groups, assessed prognostic markers and provided insights into the effects of targeted pulmonary vascular treatment in severe PH-COPD. This underscores the importance of thorough assessment and accurate classification to ensure appropriate management and prudent use of costly therapies. This registry also provides detailed phenotypic information which may be helpful when defining entry criteria for clinical trials.

The characterization of this patient cohort has also lead to a number of publications from collaborative projects in the Academic Unit of Radiology.