Geert Kleinnibbelink

General Introduction and Outline of Thesis 21 1 - Group 1: Pulmonary arterial hypertension - Group 2: Pulmonary hypertension due to left heart disease - Group 3. Pulmonary hypertension due to lung diseases and/or hypoxia - Group 4: Chronic thromboembolic pulmonary hypertension and other pulmonary artery obstructions - Group 5: Pulmonary hypertension with unclear and/or multifactorial mechanisms Pulmonary arterial hypertension (PAH) is a clinical condition characterized by the presence of pre-capillary PH and pulmonary vascular resistance > 3 Wood units, in the absence of other causes of pre-capillary PH such as PH due to lung diseases, chronic thromboembolic PH, or other rare diseases. 34 In PAH, as a consequence of an increased resistance in the pulmonary artery there is a greater drive for the RV to produce an increased pressure to circulate the same amount of blood. Facing this continuous pressure-overload, the RV will remodel. As a consequence, the RV becomes hypertrophied and dilated, whilst in a later stage dysfunction occurs which might lead to RV heart failure. 5, 36 The gold standard for diagnosis of PH is a RHC. 34 RHC is an invasive, time-consuming and expensive procedure with a relative risk of complications. Since the previous decade, vasodilators have been introduced into the treatment of PH and have improved life- expectancy. 37 Although RV function may be the most important factor with regards to prognosis, direct measures of RV function are not routinely used into the follow-up of the patients’ condition and/or risk stratification. 34 Currently, risk assessment in PH is based on clinical signs of right heart failure, progression of symptoms, functional classification, 6-minute walk test, cardiopulmonary exercise testing, NT-proBNP and invasively obtained haemodynamic characteristics. These current guidelines utilise only right atrial size and the presence of pericardial effusion into account as determined by echocardiography. 34 Due to the complex RV geometry and load dependency of RV functional parameters, traditional echocardiographic indices such as RV fractional area change (RVFAC) and tricuspid annular plane systolic excursion (TAPSE) have limited prognostic power in patients with PAH. 38