Morphological substrates for atrial arrhythmogenesis in a heart with atrioventricular septal defect

Research output: Contribution to journalArticle

Authors

  • Jack Rowley-Nobel
  • Caroline B Jones
  • Rafael Guerrero
  • Tristan Lowe
  • Jichao Zhao
  • Henggui Zhang
  • Jonathan C Jarvis

Colleges, School and Institutes

External organisations

  • University of Cambridge
  • Department of Cardiology, Alder Hey Children's Hospital, Liverpool, United Kingdom.
  • Department of Cardiac Surgery, Alder Hey Children's Hospital, Liverpool, United Kingdom.
  • University of Manchester
  • Auckland Bioengineering Institute, Auckland University, Auckland, New Zealand.
  • Liverpool John Moores University

Abstract

Due to advances in corrective surgery, congenital heart disease has an ever growing patient population. Atrial arrhythmias are frequently observed pre- and post-surgical correction. Pharmaceutical antiarrhythmic therapy is not always effective, therefore many symptomatic patients undergo catheter ablation therapy. In patients with atrioventricular septal defects (AVSD), ablation therapy itself has mixed success; arrhythmogenic recurrences are common, and because of the anatomical displacement of the atrioventricular node, 3-degree heart block post-ablation is a real concern. In order to develop optimal and safe ablation strategies, the field of congenital cardiac electrophysiology must combine knowledge from clinical electrophysiology with a thorough understanding of the anatomical substrates for arrhythmias. Using image-based analysis and multi-cellular mathematical modeling of electrical activation, we show how the anatomical alterations characteristic of an AVSD serve as arrhythmogenic substrates. Using ex-vivo contrast enhanced micro-computed tomography we imaged post-mortem the heart of a 5 month old male with AVSD at an isometric spatial resolution of 38 μm. Morphological analysis revealed the 3D disposition of the cardiac conduction system for the first time in an intact heart with this human congenital malformation. We observed displacement of the compact atrioventricular node inferiorly to the ostium of the coronary sinus. Myocyte orientation analysis revealed that the normal arrangement of the major atrial muscle bundles was preserved but was modified in the septal region. Models of electrical activation suggest the disposition of the myocytes within the atrial muscle bundles associated with the "fast pathway," together with the displaced atrioventricular node, serve as potential substrates for re-entry and possibly atrial fibrillation. This study used archived human hearts, showing them to be a valuable resource for the mathematical modeling community, and opening new possibilities for the investigations of arrhythmogenesis and ablation strategies in the congenitally malformed heart.

Details

Original languageEnglish
Article number1071
Number of pages12
JournalFrontiers in Physiology
Volume9
Publication statusPublished - 23 Aug 2018

Keywords

  • arrhythmias cardiac, atrial fibrillation (AF), re-entry, micro-computed tomography, mathematical modeling, myocyte orientation, congenital heart disease (CHD), atrioventricular septal defect