Anne-Marie Koop

308 In the last decades, the impact of right ventricular (RV) function on clinical status has become increasingly clear. 1-4 The RV is no longer considered as a mirrored copy of the left ventricle (LV) due to many differences in embryonic origin, anatomy and physiology. 5 Hereby, the need for further understanding of the etiology of RV failure in different forms of heart failure has been recognized. 6 Recently, in 2018, this need has been translated in a scientific statement focusing on right sided heart failure. 7 However, as outlined in the introduction, underlying biological pathways involved in the development from adaptive RV remodelling towards RV failure are not specified yet. This complicates targeted invention enabling the preservation of RV function. The aim of this thesis was to identify factors of RV remodelling due to abnormal loading conditions, with a specific focus on RV metabolism and molecular mechanisms of remodelling by the use of animal models. Additionally, we performed multi-biomarker analysis in order to identify RV disease in 125 children with congenital heart disease or pulmonary hypertension. The biomarker panel represents various activated RV adaptation processes earlier studied in this thesis. In the current chapter we discuss the main findings and potential directions for further research, which may contribute to future clinical implications. Clinical right ventricular failure is characterized by diastolic dysfunction Up till now, in clinical practice, the assessment of RV function is still predominately based on systolic function by the echocardiographic derived parameter tricuspid annular plane systolic excursion (TAPSE). 5 However, in LV disease it has become increasinglyclear that diastolic dysfunction is also an important predictor of prognosis and mortality. 8,9 Moreover, the assumption that ‘RV failure is systolic failure’ has also been challengedbyvarious experimental and clinical studies, showing a deterioration of clinical function associated with increased contractility. 10-15 In chapter 2, we have shown that clinical RV failure is associated with impaired diastolic function, whereas preserved diastolic function was observed in RV dysfunction with preserved clinical function. Hereby, we conclude that RV diastolic function may play an important role in the development of clinical RV failure. Assessment of RV diastolic function predominantly relies on invasive measurements. Also we defined diastolic function by end-diastolic elastance measured by heart catheterization (chapter 2). Due to upcoming techniques, assessing RVdiastolic functionmay becomemore accessible with new echocardiographic and cardiac magnetic resonance parameters. 16 We suggest further validation of these parameters in conditions of RV pressure overload.