Anne-Marie Koop

4 157 INTRODUCTION Right ventricular (RV) failure is a main determinant for mortality and morbidity in patients with pulmonary hypertension and in patients with congenital heart diseases. 1,2 RV failure due to progressive pressure load is characterized by diastolic dysfunction and uncoupling of the RV and pulmonary vasculature. The last decade, experimental studies have identified that RV dysfunction due to pressure load is associated with RV hypertrophy, fibrosis, and metabolic derangements. 4-6 Unfortunately, the increased knowledge of the cellular signature of RV dysfunction has not yet evolved into a RV specific therapy. 7 Also, the use of therapeutic strategies developed for left heart failure, e.g. ischemic heart diseases or hypertension, has not led to significant clinical improvements in patients with RV disease yet. 7-9 Derangements of RV metabolism associated with RV dysfunction due to pressure load is a recognized feature in various experimental studies 4,10-18 and is confirmed in several studies in patients with pulmonary arterial hypertension (PAH) 5,19,20 . The RV under pressure has been shown to be vulnerable to changes in coronary perfusion pressure 1 and several experimental studies have described a state of so-called capillary rarefaction, 4,21,22 both of which may add to the metabolic derangements. The metabolic changes described involve suppression of genes involved in fatty acid metabolism 4,10,12-15,18,23,24 , as well as deviation away from the glucose oxidation pathway 4,10,11,13,14,18,23 . More recently, studies are focusing on alterations in cardiac lipid content and it’s potential harmful effect. Up to now only lipotoxicity has been recognized in the pressure loaded RV in a model of bone morphogenetic receptor type 2 (BMPR2)-mutation. 12 However, also myocardial shortage of lipids has been suggested to have negative reflections on cardiac remodelling and function. 25 Together these observations emphasizes the relevance of a deeper understanding of RV dysfunction induced by different types of disease and the therapeutic potential of lipid modulation therapies. Hereby, it is necessary to expand our knowledge on early and temporal changes in RV metabolic derangements during disease progression and its relation with functional cardiac performance. This will help to understand whether metabolic modulation is a potential therapeutic candidate in RV pressure load as has been suggested in left heart failure. 26-30 Here, we aimed to characterize the alterations in RV lipid content during chronic pressure load and to assess its correlation with RV-function, -remodelling and – metabolism over time.