Anne-Marie Koop

314 of RV pressure load, whereas hsTnT enables identification of severe RV pressure load specifically. NT-proBNP, hsTnT, MR-proADM, GDF-15, MPO and ET-1 were associated with RVH, which may reflect activation of broad spectrum of molecular processes, includingprocesses involved in theRAAS-system, cardiomyocytedecay, inflammation, metabolism, oxidative stress and fibrosis. Based on the results, we suggested a hypothetical algorithm to recognize abnormal RV loading and remodelling, leading to potential therapeutic directions. The study in chapter 8 included predominantly children with preserved functional class, so this algorithm may contribute after validation to early detection of RV disease in this specific group of patients. Combining the use of plasma derived biomarkers with the advanced imaging technique in order to assess morphologic alternations and metabolic processes, may further enable early recognition of RV adaptation. This may initiate early interventions in order to prevent progression of RV disease. Concluding remarks and future prospects This thesis emphasizes the differences, and at the same time the interplay, between the RV and LV, where the molecular processes identified in the LV cannot be copied to the RV. This implies that all the pathological processes involved in LV adaptation also should be studied in the RV. Furthermore, this thesis demonstrates that the affected metabolic processes in the abnormally loaded RV depend on the experimental model used and the associated disease etiologies. These findings stress the dynamic character of metabolic processes, which makes standardization of experimental methods pivotal to draw robust conclusions. Increased pressure affects metabolic processes in the RV, therefore metabolic biomarkers or metabolites, such as intracardiac lipids, may serve as markers of RV adaptation. This would allow implementation of metabolic profiling, as an unbiased approach to define the state of the loaded RV in clinical practice. We showed that blood derived biomarkers reflect RV adaptation in early RV disease before the occurrence of clinical signs. These techniques will enable the possibility for early interventions in order to preserve RV function in conditions of increased pressure load. Development of biomarker based algorithms may contribute to the early detection of right ventricular disease.

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