Said, F. (Fatema) (2018) Serially measured N-terminal pro B-type natriuretic peptide, cardiac troponin T, noradrenaline and adrenaline as valuable prognostic serum biomarkers in pediatric pulmonary arterial hypertension. thesis, Medicine.
Full text available on request.Abstract
Pediatric pulmonary arterial hypertension (PAH) is a rare, fatal and progressive disease with an unpredictable course and without optimal treatment. Non-invasive serum biomarkers with prognostic value over the entire disease course are needed to aid in disease management. In the current medicinal treatment, several “PAH-specific” drugs are added throughout the disease course to tackle disease progression. However, little has been reported on the effect of the add-on therapy and the optimal timing of therapy escalation. N-terminal pro B-type natriuretic peptide (NT-proBNP), cardiac troponin T (cTnT), (nor)adrenaline and dopamine are serum biomarkers released by the right ventricle (RV) and adrenal glands in response to increased wall stress, cardiomyocyte damage, and increased sympathetic activity, respectively. In this thesis we hypothesize that these serum biomarkers may reflect changes in disease severity and therefore be of prognostic value. The aim of this thesis is to investigate the association between serial serum biomarker levels with disease severity parameters (World Health Organization functional class, 6 minute walking distance and Tricuspid Annular Plane Systolic Excursion (an echocardiographic measure of longitudinal displacement of the RV)) and outcome (death or lung/heart-lung transplantation) and to determine the effect of PAH-targeted therapy on serum biomarker values and disease severity in children with PAH. For this we used linear mixed effects modelling and time-dependent Cox regression analyses. We found serum levels of NT-proBNP, cTnT and (nor)adrenaline to be significantly associated with disease severity and outcome. The effect of PAH-targeted therapy on serum biomarker levels and disease severity was assessed using paired tests. Treatment initiation decreased disease severity parameters and serum NT-proBNP levels. Add-on therapy had no significant effect on disease severity or serum biomarker levels. In conclusion, this thesis shows that monitoring serum NT-proBNP, cTnT, noradrenaline and adrenaline, at any time in the disease course, may aid in assessing disease severity and prediction of outcome, and that treatment initiation significantly decreases disease severity and ventricular wall tension.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Supervisors: and Berger, Prof. dr. RMF and Haarman, MG MSc and Beatrix Children’s Hospital – Department of Pediatric Cardio and University Medical Center Groningen and University of Groningen |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 10:42 |
| Last Modified: | 25 Jun 2020 10:42 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/371 |
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