Revisiting the development of the atrioventricular conduction axis

BACKGROUND: The precise steps involved in development of the atrioventricular conduction axis remain incompletely understood, despite over a century of anatomical and histological studies. Recent advances in imaging, and access to human embryonic and fetal heart specimens, offer new insights into this process. OBJECTIVE: To clarify the morphological remodeling and insulation of the atrioventricular conduction axis during late embryonic and early fetal human heart development, with emphasis on the fate of nodoventricular and fasciculo-ventricular pathways. METHODS: Serial histological sections and micro-computed tomographic datasets encompassing Carnegie stage 17 through 23, until the end of the fetal period, including a newborn (42 weeks of development), from the Human Developmental Biology Resource, and additional fetal heart archives, were analyzed. Reproducibility was assessed by blinded interobserver evaluation. RESULTS: The atrioventricular conduction axis arises, in part, from a drape of trabecular cardiomyocytes on the septal crest, which remodels into the branching and non-branching bundles. It also includes the so-called "primary ring". During fetal development, expansion of the atrioventricular junctions, producing the inferior pyramidal space, centralizes the compact atrioventricular node, and disrupts most nodoventricular pathways. Fasciculo-ventricular connections, in contrast, largely persist, with some myocardial connections remaining throughout gestation. Part of the primary ring becomes the retro-aortic node. CONCLUSION: Remodeling of the atrioventricular conduction axis is characterized by dynamic reorganization and selective insulation of specialized cardiomyocytes. Persistence of fasciculo-ventricular pathways, and loss of nodoventricular connections, has obvious implications for the understanding of the postnatal anatomy of the conduction system anatomy and its arrhythmogenic substrates.