Pulmonary hypertension: clinical phenotypes and non-invasive risk stratification

Pulmonary arterial hypertension (PAH) is a rare disease and often heterogeneous at clinical presentation. There has been significant interest in the use of clinical parameters to assess risk, and two risk stratification tools exist. I aimed to assess whether additional non-invasive investigations could improve upon current approaches. In addition, I sought to evaluate specific phenotypes in pulmonary hypertension, including patients with idiopathic PAH (IPAH) who have mild lung disease. Data were obtained from clinical databases at a large PAH referral centre.
When assessing clinical phenotypes, I identified that the presence of minor lung disease in patients with IPAH was a strongly negative prognostic marker, and these patients did not demonstrate an improvement in exercise capacity in response to PAH targeted therapy.
For risk stratification I aimed to identify thresholds for low (<5%), intermediate (5-10%) and high (>10%) risk of one-year mortality, as in other widely-used approaches. Risk could be stratified using three non-invasive assessments: cardiac MRI, incremental shuttle walking test (ISWT) and emPHasis-10 quality of life score. In contrast to current risk stratification approaches, thresholds for cardiac MRI were able to identify a large proportion of patients (63%) at low-risk of one-year mortality. In addition, cardiac MRI was able to add discriminative value to currently used risk stratification scores. EmPHasis-10 was an independent predictor of mortality, and in a risk stratification approach was able to identify patients with distinct levels of one-year mortality. For the ISWT, a 10% improvement in exercise capacity was an independent prognostic marker of survival, and thresholds derived at baseline accurately stratified risk at follow-up.
This thesis demonstrates that non-invasive assessments can be used either in isolation or in conjunction with other prognostic parameters in patients with PAH. The thresholds proposed could be considered for incorporation into widely-used risk stratification scores.