Pulmonary hypertension (PH) is a life-limiting, heterogeneous condition that affects approximately 1% of the population. Its symptomatology is characterised predominantly by progressively worsening exertional dyspnoea. Common disorders of the lung and heart are responsible for the majority of cases but the pulmonary arterial hypertension (PAH) phenotype is rare.
PH is defined according to the haemodynamic criteria of an elevated mean pulmonary arterial pressure (mPAP) >20 mmHg. PH can further be classified into five groups according to haemodynamic criteria and clinical features. Individuals with systemic sclerosis (SSc) have a higher lifetime prevalence of PAH at 6.4-9%.
Chapter 1 provides an in-depth literature review of the epidemiological, pathophysiological and clinical features of pulmonary hypertension, as well as a detailed analysis of current recommended investigations and management pathways. PH-SSc phenotypes are defined; hypotheses are generated.
Chapter 2 outlines the overall methods used in the research parts of the thesis. Data is from the single-centre Assessing the Spectrum of Pulmonary hypertension Identified at a REferral centre (ASPIRE) registry.
Chapter 3 assesses the spectrum of PH phenotypes in patients with SSc and characterised survival according to haemodynamics, lung function and multimodality imaging. Those with a chronic lung disease SSc-PH phenotype had inferior survival. Survival improved when comparing the cohorts from 2000-2012 to 2012-2020 together with pharmacological advances.
Chapter 4 examines the diagnostic utility of gas transfer parameters in patients with SSc with and without lung disease. DLco% performs as least as strongly as Kco% or FVC%/DLco% in ROC analysis and in correlation with mPAP.
In conclusion this thesis demonstrates the existence of distinct clinical phenotypes in SSc-PH and their respective differences in survival times. Spirometry and gas transfer measures show clear diagnostic utility. Further work is needed to demonstrate if patients classified as having SSc-PH following lowering of diagnostic thresholds respond to available pharmacological treatments.
