afterload-reducing agents including enalapril651 and losartan652 did not improve exercise capacity in patients with TGA after the atrial switch operation or those with congenitally corrected TGA Possible causes include minimal baseline activation of the renin-angiotensin system652 and limited preload due to impairment of atrioventricular transport.650,653 The Future A comprehensive understanding of the normal functioning of the systemic circulation requires its appraisal from the structural, physiologic, and mechanical perspectives The role of systemic arterial dysfunction as a risk factor and a probable etiologic factor for cardiovascular disease has been better defined in adults in the past two decades Concurrent development of noninvasive methodologies for the assessment of systemic arterial function and structure has led to their increasing utilization in children Consequently the list of childhood conditions associated with arterial dysfunction has expanded rapidly, although the underlying mechanisms of arterial dysfunction in the young clearly require further exploration In vivo metabolic and molecular imaging of the arterial system would help to elucidate the biology of arterial dysfunction, whereas noninvasive four-dimensional flow imaging would further improve our understanding of physiologic and pathophysiologic blood flow conditions in the young Although strategies to reduce arterial stiffness and improve endothelial dysfunction have been proposed and their potential benefits demonstrated in selected high-risk cohorts of pediatric patients, their benefits in otherwise healthy children remain unknown Longitudinal studies are required to determine whether systemic arterial dysfunction tracks from childhood to adulthood Longterm outcome studies would determine whether arterial dysfunction in the young represents a genuine risk factor that would affect cardiovascular health in adulthood Such evidence-based data are eagerly awaited Advances in molecular biology have unveiled some of the genetic determinants of vascular structure and function However, translating the genomic information into clinical and personalized medicine for the management of arterial dysfunction will require a quantum leap Optimal interaction between the systemic circulation and the systemic ventricle is instrumental in ensuring the normal functioning of the cardiovascular system A better understanding of ventriculoarterial coupling in pediatric cardiac conditions, in particular congenital heart disease associated with systemic ventricular dysfunction, would shed light on the choice of the most appropriate management strategy This is of particular relevance given that heart failure has become an important issue in the expanding population of older children and adults with congenital heart disease Annonated References Dalla Pozza R, Ehringer-Schetitska D, Fritsch P, et al Intima media thickness measurement in children: a statement from the association for European paediatric cardiology (AEPC) working group on cardiovascular prevention endorsed by the association for European paediatric cardiology Atherosclerosis 2015;238:380–387 Urbina EM, Williams RV, Alpert BS, et al Noninvasive assessment of subclinical atherosclerosis in children and adolescents: recommendations for standard assessment for clinical research: a scientific statement from the American Heart Association Hypertension 2009;54:919–950 These statements review the methodologies for the noninvasive assessment of subclinical atherosclerosis in children and adolescents, provide normative data, and make recommendations for the standardization of tools for assessing intima-media thickness, arterial stiffness, and endothelial function Deanfield JE, Halcox JP, Rabelink TJ Endothelial function and dysfunction: testing and clinical relevance Circulation 2007;115:1285–1295 ... children: a statement from the association for European paediatric cardiology (AEPC) working group on cardiovascular prevention endorsed by the association for European paediatric cardiology Atherosclerosis 2015;238:380–387... functioning of the cardiovascular system A better understanding of ventriculoarterial coupling in pediatric cardiac conditions, in particular congenital heart disease associated with systemic ventricular dysfunction, would... dysfunction have been proposed and their potential benefits demonstrated in selected high-risk cohorts of pediatric patients, their benefits in otherwise healthy children remain unknown Longitudinal studies are required to determine