Atrial fibrillation driven by micro-anatomic intramural re-entry revealed by simultaneous sub-epicardial and sub-endocardial optical mapping in explanted human hearts

Brian J. Hansen, Jichao Zhao, Thomas A. Csepe, Brandon T. Moore, Ning Li, Laura A. Jayne, Anuradha Kalyanasundaram, Praise Lim, Anna Bratasz, Kimerly A. Powell, Orlando P. Simonetti, Robert S.D. Higgins, Ahmet Kilic, Peter J. Mohler, Paul M.L. Janssen, Raul Weiss, John D. Hummel, Vadim V. Fedorov

Research output: Contribution to journalArticlepeer-review

Abstract

Aims The complex architecture of the human atria may create physical substrates for sustained re-entry to drive atrial fibrillation (AF). The existence of sustained, anatomically defined AF drivers in humans has been challenged partly due to the lack of simultaneous endocardial-epicardial (Endo-Epi) mapping coupled with high-resolution 3D structural imaging. Methods and results Coronary-perfused human right atria from explanted diseased hearts (n = 8, 43-72 years old) were optically mapped simultaneously by three high-resolution CMOS cameras (two aligned Endo-Epi views (330 μm2 resolution) and one panoramic view). 3D gadolinium-enhanced magnetic resonance imaging (GE-MRI, 80 μm3 resolution) revealed the atrial wall structure varied in thickness (1.0 ± 0.7-6.8 ± 2.4 mm), transmural fiber angle differences, and interstitial fibrosis causing transmural activation delay from 23 ± 11 to 43 ± 22 ms at increased pacing rates. Sustained AF (>90 min) was induced by burst pacing during pinacidil (30-100 μM) perfusion. Dual-sided sub-Endo-sub-Epi optical mapping revealed that AF was driven by spatially and temporally stable intramural re-entry with 107 ± 50 ms cycle length and transmural activation delay of 67 ± 31 ms. Intramural re-entrant drivers were captured primarily by sub-Endo mapping, while sub-Epi mapping visualized re-entry or 'breakthrough' patterns. Re-entrant drivers were anchored on 3D micro-anatomic tracks (15.4 ± 2.2 × 6.0 ± 2.3 mm2, 2.9 ± 0.9 mm depth) formed by atrial musculature characterized by increased transmural fiber angle differences and interstitial fibrosis. Targeted radiofrequency ablation of the tracks verified these re-entries as drivers of AF. Conclusions Integrated 3D structural-functional mapping of diseased human right atria ex vivo revealed that the complex atrial microstructure caused significant differences between Endo vs. Epi activation during pacing and sustained AF driven by intramural re-entry anchored to fibrosis-insulated atrial bundles.

Original languageEnglish (US)
Pages (from-to)2390-2401
Number of pages12
JournalEuropean heart journal
Volume36
Issue number35
DOIs
StatePublished - Sep 14 2015
Externally publishedYes

Keywords

  • Atrial fibrillation
  • Catheter radiofrequency ablation
  • Fibrosis
  • Gadolinium-enhanced MRI
  • Intramural re-entry
  • Optical mapping
  • Rotor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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