Three-dimensional integrated functional, structural, and computational mapping to define the structural "fingerprints" of heart-specific atrial fibrillation drivers in human heart ex vivo

Jichao Zhao, Brian J. Hansen, Yufeng Wang, Thomas A. Csepe, Lidiya V. Sul, Alan Tang, Yiming Yuan, Ning Li, Anna Bratasz, Kimerly A. Powell, Ahmet Kilic, Peter J. Mohler, Paul M.L. Janssen, Raul Weiss, Orlando P. Simonetti, John D. Hummel, Vadim V. Fedorov

Research output: Contribution to journalArticle

Abstract

Background--Structural remodeling of human atria plays a key role in sustaining atrial fibrillation (AF), but insufficient quantitative analysis of human atrial structure impedes the treatment of AF. We aimed to develop a novel 3-dimensional (3D) structural and computational simulation analysis tool that could reveal the structural contributors to human reentrant AF drivers. Methods and Results--High-resolution panoramic epicardial optical mapping of the coronary-perfused explanted intact human atria (63-year-old woman, chronic hypertension, heart weight 608 g) was conducted during sinus rhythm and sustained AF maintained by spatially stable reentrant AF drivers in the left and right atrium. The whole atria (107961985 mm3) were then imaged with contrast-enhancement MRI (9.4 T, 180×180×360-μm3 resolution). The entire 3D human atria were analyzed for wall thickness (0.4-11.7 mm), myofiber orientations, and transmural fibrosis (36.9% subendocardium; 14.2% midwall; 3.4% subepicardium). The 3D computational analysis revealed that a specific combination of wall thickness and fibrosis ranges were primarily present in the optically defined AF driver regions versus nondriver tissue. Finally, a 3D human heart-specific atrial computer model was developed by integrating 3D structural and functional mapping data to test AF induction, maintenance, and ablation strategies. This 3D model reproduced the optically defined reentrant AF drivers, which were uninducible when fibrosis and myofiber anisotropy were removed from the model. Conclusions--Our novel 3D computational high-resolution framework may be used to quantitatively analyze structural substrates, such as wall thickness, myofiber orientation, and fibrosis, underlying localized AF drivers, and aid the development of new patientspecific treatments.

Original languageEnglish (US)
Article numbere005922
JournalJournal of the American Heart Association
Volume6
Issue number8
DOIs
StatePublished - Aug 1 2017
Externally publishedYes

Keywords

  • 3D computer model
  • Atrial fibrillation
  • Atrial structure
  • Computer-based model
  • Fiber architecture
  • Fibrosis
  • Human atria
  • Reentry
  • Wall thickness

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Zhao, J., Hansen, B. J., Wang, Y., Csepe, T. A., Sul, L. V., Tang, A., Yuan, Y., Li, N., Bratasz, A., Powell, K. A., Kilic, A., Mohler, P. J., Janssen, P. M. L., Weiss, R., Simonetti, O. P., Hummel, J. D., & Fedorov, V. V. (2017). Three-dimensional integrated functional, structural, and computational mapping to define the structural "fingerprints" of heart-specific atrial fibrillation drivers in human heart ex vivo. Journal of the American Heart Association, 6(8), [e005922]. https://doi.org/10.1161/JAHA.117.005922