Early detection of pre-capillary pulmonary hypertension

The focus in my thesis is on two forms of treatable pre-capillary pulmonary hypertension (PH): pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). In patients with pulmonary arterial hypertension (PAH), pulmonary vascular resistance (PVR) is increased due to abnormal proliferation of endothelial cells, smooth muscle cell hypertrophy and vasoconstriction. In patients with CTEPH, fibrotic intravascular material causes narrowing/occlusion of the (small) pulmonary arteries (2). In PAH and CTEPH alike, the right ventricle (RV) adapts to the increased pressures by enhancing contractility and by increasing wall thickness via hypertrophy (3). Current treatment options for pre-capillary PH decrease the PVR and thereby reduce the RV afterload. Afterload is rarely normalized, however, except perhaps after lung transplantation or pulmonary endarterectomy for CTEPH. When pulmonary hypertension is sustained or even progressive, RV adaptation will ultimately fail. The RV begins to dilate, cardiac output will decrease and in the final stage the RV fails. As the status of the RV determines prognosis, early detection of pre-capillary PH is of great value to prevent/delay RV failure. Early detection of pre-capillary PH allows early and aggressive treatment which is associated with improved outcome (4, 5). However, due to its rarity and nonspecific clinical presentation, pre-capillary PH is usually diagnosed late in the disease course when RV failure already occurs. In this thesis, we focused on the improvement of early detection of pre-capillary PH.