Anne-Marie Koop

9 313 This makes adequate pressure measurements necessary before cardiac function is affected influencing the pressure gradient across the PAB. Intermodel comparison (i.e. models of pulmonary arterial hypertension versus fixed afterload by pulmonary artery banding or clipping) of the degree of pressure load is challenging since right ventricular systolic pressure is not always measured and different derivatives have to be used in the different models (pulmonary artery acceleration time (PAAT) versus PAB-gradient respectively). This, in combination with the different disease etiology, makes that caution is advised when drawing any model-transcending conclusions. In the current thesis, we attempted to do so in chapter 3 regarding metabolic outcome parameters. Integrating the results of multiple experiments and models is most optimal when experimental methods are standardized. Publication of protocols, as we did in chapter 5 , may help to reduce affiliation related bias and hopefully stimulates joint publications by different research groups. Translating experimental findings to clinical practice The use of biomarkers in clinical practice has been rapidlyexpanded over the last years. Both biomarkers derived fromblood and several imaging techniquesmaycontribute to early diagnosis and offer guidance in the follow-up of patients with chronic disease. 77-79 These markers serve as a surrogate of pathophysiological processes. In heart failure, well-known biomarkers are NT-proBNP and troponine, representing myocardial stretch and decay respectively. 81-84 The selection of biomarkers is expanding, adding markers for processes as neuroendocrine activation, inflammation, metabolism and fibrosis. 80, 85-89 This may help to increase the recognition of cardiac remodelling in early stages of cardiac stress. Although their potential use is more and more clarified, clinical implementation remains sparse. This doesn’t hold back the research studying the additional value of these biomarkers. Combing multiple biomarkers, and hereby creating subsequent biomarker profiles, is a promising technique to develop more advanced characterizations of particular groups of patients. This has been done for heart failurewith preserved, mid-range and reduced ejection fraction (HFpEF, HFmrEF, and HFrEF respectively), deriving more insights in processes of molecular remodelling in the heterogeneous group of patients with HFmrEF. 90 In chapter 8 we performed multi-biomarker analysis in children with (a history of) abnormal loading conditions and profiled plasma-derived biomarker expression according to type and degree of loading. Although the pattern of the biomarker profiles seemed to be comparable, the expression level of the biomarkers differed between the groups representing different levels of molecular remodelling. In addition, NT-proBNP and ET-1 enable identification Characterization of the various models will be necessary to enable differentiation between common denominators as the result of RV pressure load and effects of the specific stimulus.