Fibrosis Microstructure Modulates Reentry in Non-ischemic Dilated Cardiomyopathy: Insights From Imaged Guided 2D Computational Modeling
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Author(s)
Type
Journal Article
Abstract
Aims: Patients who present with non-ischemic dilated cardiomyopathy (NIDCM) and
enhancement on late gadolinium magnetic resonance imaging (LGE-CMR), are at high
risk of sudden cardiac death (SCD). Further risk stratification of these patients based
on LGE-CMR may be improved through better understanding of fibrosis microstructure.
Our aim is to examine variations in fibrosis microstructure based on LGE imaging, and
quantify the effect on reentry inducibility and mechanism. Furthermore, we examine the
relationship between transmural activation time differences and reentry.
Methods and Results: 2D Computational models were created from a single short axis
LGE-CMR image, with 401 variations in fibrosis type (interstitial, replacement) and density,
as well as presence or absence of reduced conductivity (RC). Transmural activation
times (TAT) were measured, as well as reentry incidence and mechanism. Reentries
were inducible above specific density thresholds (0.8, 0.6 for interstitial, replacement
fibrosis). RC reduced these thresholds (0.3, 0.4 for interstitial, replacement fibrosis) and
increased reentry incidence (48 no RC vs. 133 with RC). Reentries were classified as rotor,
micro-reentry, or macro-reentry and depended on fibrosis micro-structure. Differences
in TAT at coupling intervals 210 and 500ms predicted reentry in the models (sensitivity
89%, specificity 93%). A sensitivity analysis of TAT and reentry incidence showed that
these quantities were robust to small changes in the pacing location.
Conclusion: Computational models of fibrosis micro-structure underlying areas of
LGE in NIDCM provide insight into the mechanisms and inducibility of reentry, and
their dependence upon the type and density of fibrosis. Transmural activation times,
measured at the central extent of the scar, can potentially differentiate microstructures
which support reentry.
enhancement on late gadolinium magnetic resonance imaging (LGE-CMR), are at high
risk of sudden cardiac death (SCD). Further risk stratification of these patients based
on LGE-CMR may be improved through better understanding of fibrosis microstructure.
Our aim is to examine variations in fibrosis microstructure based on LGE imaging, and
quantify the effect on reentry inducibility and mechanism. Furthermore, we examine the
relationship between transmural activation time differences and reentry.
Methods and Results: 2D Computational models were created from a single short axis
LGE-CMR image, with 401 variations in fibrosis type (interstitial, replacement) and density,
as well as presence or absence of reduced conductivity (RC). Transmural activation
times (TAT) were measured, as well as reentry incidence and mechanism. Reentries
were inducible above specific density thresholds (0.8, 0.6 for interstitial, replacement
fibrosis). RC reduced these thresholds (0.3, 0.4 for interstitial, replacement fibrosis) and
increased reentry incidence (48 no RC vs. 133 with RC). Reentries were classified as rotor,
micro-reentry, or macro-reentry and depended on fibrosis micro-structure. Differences
in TAT at coupling intervals 210 and 500ms predicted reentry in the models (sensitivity
89%, specificity 93%). A sensitivity analysis of TAT and reentry incidence showed that
these quantities were robust to small changes in the pacing location.
Conclusion: Computational models of fibrosis micro-structure underlying areas of
LGE in NIDCM provide insight into the mechanisms and inducibility of reentry, and
their dependence upon the type and density of fibrosis. Transmural activation times,
measured at the central extent of the scar, can potentially differentiate microstructures
which support reentry.
Date Issued
2018-12-19
Date Acceptance
2018-12-06
Citation
Frontiers in Physiology, 2018, 9
ISSN
1664-042X
Publisher
Frontiers Media
Journal / Book Title
Frontiers in Physiology
Volume
9
Copyright Statement
© 2018 Balaban, Halliday, Mendonca Costa, Bai, Porter, Rinaldi, Plank,
Rueckert, Prasad and Bishop. This is an open-access article distributed under the
terms of the Creative Commons Attribution License (CC BY). The use, distribution
or reproduction in other forums is permitted, provided the original author(s) and
the copyright owner(s) are credited and that the original publication in this journal
is cited, in accordance with accepted academic practice. No use, distribution or
reproduction is permitted which does not comply with these terms.
Rueckert, Prasad and Bishop. This is an open-access article distributed under the
terms of the Creative Commons Attribution License (CC BY). The use, distribution
or reproduction in other forums is permitted, provided the original author(s) and
the copyright owner(s) are credited and that the original publication in this journal
is cited, in accordance with accepted academic practice. No use, distribution or
reproduction is permitted which does not comply with these terms.
Sponsor
Medical Research Council (MRC)
British Heart Foundation
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000453893100001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
RTJ12028524-1
FS/15/29/31492
Subjects
Science & Technology
Life Sciences & Biomedicine
Physiology
non-ischemic cardiomiopathy
computational modeling
late gadolinium enhanced magnetic resonance imaging
dilated cardiaomypothy
electrophysiology
reentry
arrhythmia (any)
ventricular tachycardia (VT)
MYOCARDIAL-INFARCTION
BORDER ZONE
HEART
ARRHYTHMIA
CONDUCTION
DEATH
ACTIVATION
DYNAMICS
Publication Status
Published
Article Number
ARTN 1832