A multimodal approach to chronic thromboembolic pulmonary hypertension

Abstract

This thesis investigates several aspects of chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary hypertension (PH), focusing on treatment strategies, clinical outcomes, imaging techniques, and underexplored aspects of patient care. Long-term survival in patients with inoperable CTEPH was evaluated before and after the introduction of balloon pulmonary angioplasty (BPA). Overall 1-, 3-, and 5-year survival rates were 96%, 84%, and 74%, respectively. Although survival did not differ significantly between the two cohorts, BPA was independently associated with improved survival. These findings highlight the importance of BPA in the management of inoperable CTEPH. The potential of non-invasive imaging to assess treatment response following BPA was also investigated. Ventilation/perfusion scintigraphy demonstrated improved pulmonary perfusion after treatment, with semi-quantitative assessment showing better inter-observer agreement than visual assessment. However, perfusion scores did not correlate with clinical outcomes, suggesting that this imaging modality cannot replace clinical evaluation and invasive haemodynamic measurements. In addition, artificial intelligence-based analysis of computed tomography scans revealed a redistribution towards smaller pulmonary arteries following BPA. This finding may provide indirect evidence of microvascular remodelling, although further validation is required. The thesis further evaluates pretreatment with pulmonary hypertension-targeted medical therapy before BPA. Treatment was associated with improvements in clinical parameters, exercise capacity, and pulmonary haemodynamics. Patients receiving dual therapy demonstrated greater improvements in cardiac output and pulmonary vascular resistance than those receiving monotherapy or no pretreatment. Furthermore, dual therapy was associated with fewer thoracic complications during BPA and greater improvements in clinical and haemodynamic outcomes before and six months after treatment. These findings suggest that dual medical therapy may be beneficial before BPA, particularly in patients with more severe haemodynamic impairment. Tricuspid regurgitation (TR) following pulmonary endarterectomy (PEA) was also examined. TR decreased after surgery in nearly half of patients, alongside greater improvements in biomarkers and pulmonary haemodynamics. Conversely, patients with residual TR had higher pulmonary pressures and vascular resistance. Identifying patients at risk of persistent TR may help guide the selection of patients who could benefit from concomitant tricuspid valve repair. Finally, the thesis addresses two underexplored aspects of PH care: nutritional status and sexual health. Malnutrition was identified in 27% of patients according to the Global Leadership Initiative on Malnutrition criteria. Commonly used screening tools demonstrated insufficient sensitivity, potentially because they fail to adequately account for muscle wasting and fluid retention. Sexual dysfunction was also highly prevalent, affecting all men and 63% of women assessed. Most patients experienced disease-related symptoms during sexual activity, and nearly 70% expressed a desire to discuss sexuality with their healthcare provider. In conclusion, this thesis provides insights into the management of CTEPH, highlighting the potential benefits of dual medical pretreatment before BPA and the complementary role of imaging in understanding treatment effects. It also emphasises the importance of recognising residual TR, malnutrition, and sexual dysfunction to support a more comprehensive, patient-centred approach to pulmonary hypertension care.