Anne-Marie Koop

284 and remodelling. Based on the findings in this study, the discussion presents a conceptual algorithm illustrating the potential use of a multi-biomarker approach in clinical practice, which may direct and facilitate follow-up of children with CHD. METHODS Study design and population A prospective, cross-sectional observational cohort studywas performed (registered at ClinicalTrials.gov; Unique identifier: NCT04130243). Consecutive children aged 0-18 years with (a history of) RV overload who visited the outpatient clinic of the Center for Congenital Heart Disease at the University Medical Center Groningen, the Netherlands, between December 2017 and November 2018 and in whom the patient or parents/caregivers provided written informed consent, were included. Overload of the RV was categorized as either increased pressure, volume or combined volume/pressure overload. The degree of (residual) overload was scored as mild-to-moderate or severe. A group of children with a history of RV overload, but no actual residual RV overload, was included as a reference group. Detailed information regarding categorization is described in the supplemental material. Patients aged >18 years, children with a concomitant musculoskeletal disease, children under examination for non-diagnosed disease at time of investigation, and children with significant left-sided cardiac lesions were excluded from this study. Ethical approval for this study was obtained from the Medical Ethics Review Board of the University Medical Center Groningen and written informed consent from the children (and/or their guardians) was given at enrollment (reference-number 2017/190). Echocardiography All children underwent two-dimensional transthoracic echocardiography performed on a GE Vivid E9 or E95 machine (GE Healthcare, Boston, United States of America). Echocardiography was performed as part of clinical follow-up and performed according to the pediatric guidelines of the American Society of Echocardiography and included measurement of tricuspid annular plane systolic excursion (TAPSE). 25 Systolic RV function was qualitatively assessed by eyeballing and scored as good, moderate or poor. Similarly, the presence of RV hypertrophy (RVH) and RV dilatation were assessed and scored as either present or not present. Continuous wave Doppler was used to measure maximum velocities of tricuspid (TR) and pulmonary

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