Towards improved pathophysiological understanding in chronic thromboembolic pulmonary hypertension

Research output: ThesisPhd-Thesis - Research and graduation internal

Abstract

In chapter 2 the pathophysiology of acute pulmonary embolism (PE) is summarised. Central in the pathophysiology of acute PE is acute right ventricular (RV) pressure overload, leading to adaptive and ultimately maladaptive responses of the RV, with RV failure as the final common pathway. CTEPH has many similarities with acute PE. The response to an increased RV afterload, with pulmonary vascular resistance (PVR) and compliance as the main determinants of afterload, differs between CTEPH patients. In chapter 3 we analysed RV afterload and function in 21 patients with proximal CTEPH and 25 patients with distal CTEPH. While mean pulmonary artery pressure, PVR and compliance were similar, RV ejection fraction was more severely compromised and RV dilatation more pronounced in patients with proximal CTEPH. It was concluded that the site of vascular obstruction did affect RV function while lumped parameters of load were similar. Chapters 4 and 5 focused on the determinants of residual pulmonary hypertension (PH). Residual PH after pulmonary endarterectomy (PEA) is relatively frequent, but its pathophysiology is less well understood. Distal vasculopathy is assumed to be the major determinant of residual PH. In chapter 4 we analysed the role of residual (sub)segmental macrovascular lesions. In 31 patients CTPA and magnetic resonance perfusion were performed 6 months post-PEA, and compared to CTPA and MR perfusion before PEA. Although 20% of the pulmonary arteries remained abnormal after PEA, no association was found with residual PH. Residual PH was also present in patients without residual macrovascular lesions on CTPA, leading to the conclusion that remaining (sub)segmental macrovascular lesions are a contributor at most but not a major determinant of residual PH. Parenchymal perfusion as determined by MR perfusion improved after PEA, but was similar between patients with and without residual PH. In chapter 5 the role of recurrent thrombosis was analysed in 33 patients: new vascular lesions were seen on CTPA 6 months post-PEA in 27% of patients, mainly consisting of new/increased thrombus and early tapering; their presence was not associated with hemodynamic outcomes. Although new vascular lesions are frequent after PEA, their hemodynamic consequences are limited, especially when put into context with the major vascular improvements accomplished with PEA. Their origin, dynamics, and long-term consequences however, remain unknown for now. Diagnosing residual PH after PEA requires right heart catheterisation (RHC). In chapter 6 an analysis in 51 post-PEA patients was performed to evaluate the role of postoperative early hemodynamics and non-invasive diagnostic procedures in identifying patients who do not require repeat RHC because of a very low likelihood of residual PH. Early hemodynamics post-PEA should not be used to define hemodynamic success, and NT-proBNP 6 months post-PEA (cut-off 300 ng/L) had insufficient negative predictive value. Echocardiography (low PH probability) and CPET (peak VO2 ≥ 80% predicted) 6 months post-PEA could be used to exclude residual PH. Using either of these parameters would reduce the number of re-RHC to 49-65%, without missing clinically relevant cases of residual PH. While the focus of research after PEA is on residual PH, less attention has been directed towards exercise intolerance after PEA. In chapter 7 the incidence of persistent exercise intolerance after PEA and its determinants and relation with resting hemodynamics was analysed in 68 CTEPH patients. Persistent exercise intolerance, defined as peak VO2 < 80% predicted 6 months post-PEA, was present in 66% of patients, despite substantial hemodynamic improvements. Not all exercise intolerance could be explained by the presence of residual PH. Lower preoperative TLCO was a strong predictor of exercise intolerance 6 months post-PEA.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Vrije Universiteit Amsterdam
Supervisors/Advisors
  • Bogaard, Harm Jan, Supervisor
  • Meijboom, Lilian, Co-supervisor
  • Symersky, Petr, Co-supervisor
Award date14 Jun 2021
Place of Publications.l.
Publisher
Print ISBNs9789464232523
Publication statusPublished - 15 Jun 2021

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