Anne-Marie Koop

294 Pressure and volume overload are distinct entities with distinct injury and remodelling patterns which could explain the differences in multi biomarker serum profiles in children with either pressure or volume overload of the RV. Pressure overload induces initial concentric hypertrophy progressing towards eccentric hypertrophy (dilatation) in more advanced disease, whereas volume overload will induce dilatation without the preceding stage of concentric hypertrophy. 30,31 Although underlying mechanisms remain to be unraveled, one may speculate that different types of overload activate various signaling cascades in various degrees, which in turn lead to load-specific RV remodelling. This study in children with CHD and/or PH suggests that pathophysiological pathways, known from LV remodelling, are more extensively activated in RV pressure overload than in volume or combined overload. It is well known that volume overload is initially better, or longer, tolerated by the RV than pressure load. Failure of the RV due to severe volume load (e.g. corrected TOF) in general takes longer than failure to severe pressure load (e.g. severe right outflow tract obstruction or PH). The fact that isolated RV volume overload in this pediatric study did not induce pronounced elevation of biomarkers may be due to the young age of the patients and relative short existence of RV overload when compared to adults with long standing volume loaded RV’s. In other words: in this pediatric study, the duration and impact of volume overload might have been too short to induce significant changes in biomarker plasma levels. Previous studies that reported increased levels of NT-proBNP in pediatric patients with repaired TOF included patients with combined RV overload instead of isolated volume overload. 32,33 In line with our results, a previous study in children with repaired TOF with isolated volume overload also failed to demonstrate an association with plasma levels of NT-proBNP. 33 Along the same line of reasoning: elevated levels of hsTnT have been shown in patients with CHD and are clinically relevant, because of its relation with increased risk for cardiovascular events, as death, heart failure and hospitalization. 34 However, in patients with RV volume load the actual relation between hsTnT plasma level and worse RV function and remodelling has been shown only in adult patients with repaired TOF. 35