Clinical worsening in Chronic Thromboembolic Pulmonary Hypertension

Abstract

Chronic thromboembolic pulmonary hypertension (CTEPH) is defined as a raised mean pulmonary artery pressure (of at least 25 mmHg at rest) caused by persistent obstruction of pulmonary arteries after pulmonary embolism that has not resolved despite at least 3 months of therapeutic anticoagulation. Non-resolving acute pulmonary embolism is the most common cause of CTEPH, and can occur after one or multiple episodes. CTEPH might occasionally develop owing to in-situ pulmonary artery thrombosis, which could be associated with inflammation of the vessel walls. The estimated prevalence of CTEPH two years after acute pulmonary embolism is 0.1-4.0%. Pulmonary endarterectomy (PEA) is the treatment of choice, offering immediate hemodynamic benefits and providing a potential cure for many patients. However, PEA is not possible for about 50% of patients (inoperable CTEPH), due to either distal pulmonary vascular obstruction that is surgically inaccessible or significant comorbidities thought to be associated with unacceptably high risk. Furthermore, in CTEPH patients with disease amenable to surgery, approximately 10% to 15% of patients have residual pulmonary hypertenion (PH, mean pulmonary arterial pressure [mPAP] > 25 mmHg) after PEA (persistent/recurrent post-operative PH). In these situations, medical treatment might be useful. Recently, clinical worsening (CW) has been used as a composite endpoint in pulmonary arterial hypertension (PAH) trials, as described by McLaughlin. It is a combination of mortality and different morbidity parameters described after the initiation of specific PH therapy. The definition most frequently used is a combination of all-cause mortality, non-elective hospital stay for PH to initiate intravenous prostanoid or lung transplantation, and disease progression defined as a reduction from baseline in six-minutes walking distance (6-MWD) by 15%.

This thesis concerns the outcome of patients with operable and inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Chapter 2 concerns the incidence of clinical worsening in patients with inoperable CTEPH in a single center population and in chapter 3 we describe the occurrence of clinical worsening in patients with CTEPH who underwent pulmonary endarterectomy (PEA). Chapter 4 and chapter 5 provide us the important role of cardiovascular imaging modalities like echocardiography and computed tomography in the pre-operative prediction of outcome after PEA. Finally, in chapter 7 the upstream pulmonary artery resistance measured by the pulmonary artery occlusion technique is evaluated as a predictor of outcome after PEA.