Abstract-Heart valve disease is an important cause of morbidity and mortality worldwide. Little is known about valve disease pathogenesis, but increasing evidence implicates a genetic basis for valve disease, suggesting a developmental origin. Although the cellular and molecular processes involved in early valvulogenesis have been well described, less is known about the regulation of valve extracellular matrix (ECM) organization and valvular interstitial cell (VIC) distribution that characterize the mature valve structure. Histochemistry, immunohistochemistry, and electron microscopy were used to examine ECM organization, VIC distribution, and cell proliferation during late valvulogenesis in chicken and mouse. In mature valves, ECM organization is conserved across species, and developmental studies demonstrate that ECM stratification begins during late embryonic cusp remodeling and continues into postnatal life. Cell proliferation decreases concomitant with ECM stratification and VIC compartmentalization. Explanted, stenotic bicuspid aortic valves (BAVs) from pediatric patients were also examined. The diseased valves exhibited disruption of the highly organized ECM and VIC distribution seen in normal valves. Cusps from diseased valves were thickened with increased and disorganized collagens and proteoglycans, decreased and fragmented elastic fibers, and cellular disarray without calcification or cell proliferation. Taken together, these studies show that normal valve development is characterized by spatiotemporal coordination of ECM organization and VIC compartmentalization and that these developmental processes are disrupted in pediatric patients with diseased BAVs. Key Words: valve disease Ⅲ extracellular matrix Ⅲ valvular interstitial cells Ⅲ cardiac development V alve replacement, usually for aortic valve disease, is the second most common cardiac operation performed in the US, and the need for reintervention is common. 1,2 Little is known about valve disease pathogenesis, but increasing evidence implicates a genetic basis for valve malformation, suggesting a developmental origin. [3][4][5][6][7] Valve development is initiated with endothelial-mesenchymal transformation of the endocardium in the outflow tract and atrioventricular (AV) canal to form endocardial cushions, and this process has been extensively studied. 8,9 Endocardial cushions subsequently elongate as a result of cell proliferation and undergo expansion and remodeling of the extracellular matrix (ECM) to form the mature semilunar valve cusps and AV valve leaflets. The morphogenetic events that characterize valvulogenesis during late embryonic and postnatal development are largely unknown. 10 The mature valve structure is composed of ECM, valvular interstitial cells (VICs), and overlying endothelial cells. The ECM is composed of 3 highly organized overlapping layers with distinct mechanical properties arranged in orientation to blood flow in the semilunar and AV valves. 11,12 The primary components of these layers are collagens, proteoglycans, a...

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Characteristics of neonates with pulmonary atresia and intact ventricular septum predict type of definitive repair. A morphologically driven institutional protocol emphasizing both 2-ventricle and Fontan pathways might mitigate the negative effect of unfavorable morphology. In the current era, 85% of neonates are likely to reach a definitive surgical end point, with 2-ventricle repair achieved in an estimated 50%.

Slide tracheoplasty with cardiopulmonary bypass can be performed with low mortality in a diverse pediatric population. This technique minimizes need for early significant airway reintervention in most cases.