Clinical Electrophysiology -> Ventricular Arrhythmias -> Physiology-Pharmacology D-PO06 - Poster Session VI (ID 26) Poster

D-PO06-054 - Structural Heterogeneity In The Human RVOT: An Arrhythmogenic Substrate? (ID 686)

Abstract

Background: The right ventricular outflow tract (RVOT) is implicated in sudden cardiac death due to malignant idiopathic and inherited arrhythmias, and this risk may be exacerbated by structural heart disease. The mechanisms responsible are incompletely understood.
Objective: To investigate the hypothesis that structural heterogeneity in the RVOT is a substrate for electrical reentry.
Methods: Long-axis RVOT-RV volumes from post-mortem human hearts (age 55-80, n=4) were optically cleared (CUBIC) and diffusion labeled with wheat-germ agglutinin (WGA), and Nav1.5 and Cx43 antibodies. Submicron 3D images were acquired with a custom-built high-throughput scanned line confocal microscope (up to 25x15x0.5 mm). RVOT anisotropy was quantified with multi-scale structure tensor analysis of 3D WGA images.
Results: There were distinct structural differences between outer (subepicardial) and inner (subendocardial) RVOT (wall thickness 6.5+2 mm). Myofiber orientation was ~90° relative to the RVOT-RV axis throughout the outer wall (71+5% wall thickness), then rotated rapidly (7.4±5°/cell width) through 0° into a complex inner myostructure. Myocytes in the outer RVOT were arranged in large bundles with substantial intramural penetration of epicardial fat (>2.5mm) and interstitial fibrosis in older hearts.
Conclusion: Our novel extended-volume imaging system enables detailed reconstruction of 3D myocardial architecture in multiple human RVOT. This reveals substantial gradients in structural heterogeneity across the RVOT consistent with adjacent slow and fast conduction pathways. We argue that this provides a potential substrate for intramural reentry.
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