Anne-Marie Koop

296 increased levels of NT-proBNP increased level of hsTnT severe pressure overload accompanied by RVH and cardio-myocyte cell decay Further investigation and adjustment treatment strategy. Continue normal follow-up. standardpanel additionalmarkers Figure 3 ‘no residual overload’, ‘volume overload’ or ‘combined overload’ pressure overload or combined overload associated with myocardial stretch mild-moderate plasma levels mild-moderate pressure overload high plasma levels severe pressure overload Consider more frequent controls in outpatient clinic, dependent of biomarker plasma level. IDENTIFICATIONOF TYPEOF RV OVERLOAD increased level of MPO RV remodeling including oxidative stress and inflammation increased level of GDF-15 RV remodeling including activation of metabolic and inflammatory signaling pathways increased level of MR-proADM RV remodeling including hypertrophy and neurohormonal activation IDENTIFICATIONRV REMODELING normal plasma levels of these biomarkers elevated plasma level ≥1 of these biomarkers normal levels of NT-proBNP normal plasma level More frequent controls in outpatient clinic. Suggestion: Evaluate biomarker levels of MPO, GDF-15 and MR-proADM. elevated plasma level POTENTIALFUTURE THERAPEUTICDIRECTIONS increased levels of ET-1 pressure overload associated with inotropic and mitogenic processes consider presence of PAH Figure 3. Conceptual algorithm of potential clinical use of a blood-derived multi-biomarker approach to characterize right ventricular disease in children with congenital heart disease or pulmonary hypertension and to guide medical management decisions. NT-proBNP: N-Terminal pro-B-Type natriuretic peptide; MR- proADM: midregional proadrenomedullin; GDF-15: growth differentiation factor 15; MPO: myeloperoxidase; ET-1: endothelin-1; hsTnT: high sensitive Troponin T; PAH: pulmonary arterial hypertension; RV: right ventricle; RVH: right ventricular hypertrophy. The presence of RV remodelling in the form of RVH was associated with a change in plasma level of six biomarkers in the investigatedmulti-biomarker profile, suggesting the involvement of several remodelling pathways or processes. RVH is known as adaptation mechanism to increased pressure overload and is present already in early phases of abnormal RV loading. 45,46 The data of this study suggest activation of molecular processes involved in myocardial stretch, neurohormonal activation, metabolism, inflammation and oxidative stress, leading to fibrosis and cell decay. Plasma levels of MR-proADM and MPO were not related to type and degree of RV overload, but significantly increased in the presence of RVH. Increased plasma levels of MR-proADM in adult patients with chronic LV heart failure have been associated