Late-Gadolinium Enhancement Interface Area and Electrophysiological Simulations Predict Arrhythmic Events in Patients With Nonischemic Dilated Cardiomyopathy

Gabriel Balaban; Brian P. Halliday; Bradley Porter; Wenjia Bai; Ståle Nygåard; Ruth Owen; Suzan Hatipoglu; Nuno Dias Ferreira; Cemil Izgi; Upasana Tayal; Ben Corden; James Ware; Dudley J. Pennell; Daniel Rueckert; Gernot Plank; Christopher A. Rinaldi; Sanjay K. Prasad; Martin J. Bishop

doi:10.1016/j.jacep.2020.08.036

Late-Gadolinium Enhancement Interface Area and Electrophysiological Simulations Predict Arrhythmic Events in Patients With Nonischemic Dilated Cardiomyopathy

Gabriel Balaban, Brian P. Halliday, Bradley Porter, Wenjia Bai, Ståle Nygåard, Ruth Owen, Suzan Hatipoglu, Nuno Dias Ferreira, Cemil Izgi, Upasana Tayal, Ben Corden, James Ware, Dudley J. Pennell, Daniel Rueckert, Gernot Plank, Christopher A. Rinaldi, Sanjay K. Prasad, Martin J. Bishop^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

Objectives

This study sought to investigate whether shape-based late gadolinium enhancement (LGE) metrics and simulations of re-entrant electrical activity are associated with arrhythmic events in patients with nonischemic dilated cardiomyopathy (NIDCM).

Background

The presence of LGE predicts life-threatening ventricular arrhythmias in NIDCM; however, risk stratification remains imprecise. LGE shape and simulations of electrical activity may be able to provide additional prognostic information.

Methods

Cardiac magnetic resonance (CMR)-LGE shape metrics were computed for a cohort of 156 patients with NIDCM and visible LGE and tested retrospectively for an association with an arrhythmic composite endpoint of sudden cardiac death and ventricular tachycardia. Computational models were created from images and used in conjunction with simulated stimulation protocols to assess the potential for re-entry induction in each patient’s scar morphology. A mechanistic analysis of the simulations was carried out to explain the associations.

Results

During a median follow-up of 1,611 (interquartile range: 881 to 2,341) days, 16 patients (10.3%) met the primary endpoint. In an inverse probability weighted Cox regression, the LGE–myocardial interface area (hazard ratio [HR]: 1.75; 95% confidence interval [CI]: 1.24 to 2.47; p = 0.001), number of simulated re-entries (HR: 1.40; 95% CI: 1.23 to 1.59; p < 0.01) and LGE volume (HR: 1.44; 95% CI: 1.07 to 1.94; p = 0.02) were associated with arrhythmic events. Computational modeling revealed repolarization heterogeneity and rate-dependent block of electrical wavefronts at the LGE–myocardial interface as putative arrhythmogenic mechanisms directly related to the LGE interface area.

Conclusions

The area of interface between scar and surviving myocardium, as well as simulated re-entrant activity, are associated with an elevated risk of major arrhythmic events in patients with NIDCM and LGE and represent novel risk predictors.

Original language	English
Journal	JACC: Clinical Electrophysiology
Early online date	29 Oct 2020
DOIs	https://doi.org/10.1016/j.jacep.2020.08.036
Publication status	E-pub ahead of print - 29 Oct 2020

Keywords

arrhythmic risk
computational modeling
dilated cardiomyopathy
fibrosis
late gadolinium enhancement

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Late-Gadolinium Enhancement Interface_BALABAN_Accepted20August2020Publishedonline29October2020_GOLD CP (CC BY)Proof, 2.64 MBLicence: CC BY

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Balaban, G., Halliday, B. P., Porter, B., Bai, W., Nygåard, S., Owen, R., Hatipoglu, S., Ferreira, N. D., Izgi, C., Tayal, U., Corden, B., Ware, J., Pennell, D. J., Rueckert, D., Plank, G., Rinaldi, C. A., Prasad, S. K., & Bishop, M. J. (2020). Late-Gadolinium Enhancement Interface Area and Electrophysiological Simulations Predict Arrhythmic Events in Patients With Nonischemic Dilated Cardiomyopathy. JACC: Clinical Electrophysiology. Advance online publication. https://doi.org/10.1016/j.jacep.2020.08.036

@article{2ed9d591b6074fa48d449b7bf34d4c5b,

title = "Late-Gadolinium Enhancement Interface Area and Electrophysiological Simulations Predict Arrhythmic Events in Patients With Nonischemic Dilated Cardiomyopathy",

abstract = "ObjectivesThis study sought to investigate whether shape-based late gadolinium enhancement (LGE) metrics and simulations of re-entrant electrical activity are associated with arrhythmic events in patients with nonischemic dilated cardiomyopathy (NIDCM).BackgroundThe presence of LGE predicts life-threatening ventricular arrhythmias in NIDCM; however, risk stratification remains imprecise. LGE shape and simulations of electrical activity may be able to provide additional prognostic information.MethodsCardiac magnetic resonance (CMR)-LGE shape metrics were computed for a cohort of 156 patients with NIDCM and visible LGE and tested retrospectively for an association with an arrhythmic composite endpoint of sudden cardiac death and ventricular tachycardia. Computational models were created from images and used in conjunction with simulated stimulation protocols to assess the potential for re-entry induction in each patient{\textquoteright}s scar morphology. A mechanistic analysis of the simulations was carried out to explain the associations.ResultsDuring a median follow-up of 1,611 (interquartile range: 881 to 2,341) days, 16 patients (10.3%) met the primary endpoint. In an inverse probability weighted Cox regression, the LGE–myocardial interface area (hazard ratio [HR]: 1.75; 95% confidence interval [CI]: 1.24 to 2.47; p = 0.001), number of simulated re-entries (HR: 1.40; 95% CI: 1.23 to 1.59; p < 0.01) and LGE volume (HR: 1.44; 95% CI: 1.07 to 1.94; p = 0.02) were associated with arrhythmic events. Computational modeling revealed repolarization heterogeneity and rate-dependent block of electrical wavefronts at the LGE–myocardial interface as putative arrhythmogenic mechanisms directly related to the LGE interface area.ConclusionsThe area of interface between scar and surviving myocardium, as well as simulated re-entrant activity, are associated with an elevated risk of major arrhythmic events in patients with NIDCM and LGE and represent novel risk predictors.",

keywords = "arrhythmic risk, computational modeling, dilated cardiomyopathy, fibrosis, late gadolinium enhancement",

author = "Gabriel Balaban and Halliday, {Brian P.} and Bradley Porter and Wenjia Bai and St{\aa}le Nyg{\aa}ard and Ruth Owen and Suzan Hatipoglu and Ferreira, {Nuno Dias} and Cemil Izgi and Upasana Tayal and Ben Corden and James Ware and Pennell, {Dudley J.} and Daniel Rueckert and Gernot Plank and Rinaldi, {Christopher A.} and Prasad, {Sanjay K.} and Bishop, {Martin J.}",

year = "2020",

month = oct,

day = "29",

doi = "10.1016/j.jacep.2020.08.036",

language = "English",

journal = "JACC: Clinical Electrophysiology",

issn = "2405-500X",

publisher = "Elsevier USA",

}

Balaban, G, Halliday, BP, Porter, B, Bai, W, Nygåard, S, Owen, R, Hatipoglu, S, Ferreira, ND, Izgi, C, Tayal, U, Corden, B, Ware, J, Pennell, DJ, Rueckert, D, Plank, G, Rinaldi, CA, Prasad, SK & Bishop, MJ 2020, 'Late-Gadolinium Enhancement Interface Area and Electrophysiological Simulations Predict Arrhythmic Events in Patients With Nonischemic Dilated Cardiomyopathy', JACC: Clinical Electrophysiology. https://doi.org/10.1016/j.jacep.2020.08.036

TY - JOUR

T1 - Late-Gadolinium Enhancement Interface Area and Electrophysiological Simulations Predict Arrhythmic Events in Patients With Nonischemic Dilated Cardiomyopathy

AU - Balaban, Gabriel

AU - Halliday, Brian P.

AU - Porter, Bradley

AU - Bai, Wenjia

AU - Nygåard, Ståle

AU - Owen, Ruth

AU - Hatipoglu, Suzan

AU - Ferreira, Nuno Dias

AU - Izgi, Cemil

AU - Tayal, Upasana

AU - Corden, Ben

AU - Ware, James

AU - Pennell, Dudley J.

AU - Rueckert, Daniel

AU - Plank, Gernot

AU - Rinaldi, Christopher A.

AU - Prasad, Sanjay K.

AU - Bishop, Martin J.

PY - 2020/10/29

Y1 - 2020/10/29

N2 - ObjectivesThis study sought to investigate whether shape-based late gadolinium enhancement (LGE) metrics and simulations of re-entrant electrical activity are associated with arrhythmic events in patients with nonischemic dilated cardiomyopathy (NIDCM).BackgroundThe presence of LGE predicts life-threatening ventricular arrhythmias in NIDCM; however, risk stratification remains imprecise. LGE shape and simulations of electrical activity may be able to provide additional prognostic information.MethodsCardiac magnetic resonance (CMR)-LGE shape metrics were computed for a cohort of 156 patients with NIDCM and visible LGE and tested retrospectively for an association with an arrhythmic composite endpoint of sudden cardiac death and ventricular tachycardia. Computational models were created from images and used in conjunction with simulated stimulation protocols to assess the potential for re-entry induction in each patient’s scar morphology. A mechanistic analysis of the simulations was carried out to explain the associations.ResultsDuring a median follow-up of 1,611 (interquartile range: 881 to 2,341) days, 16 patients (10.3%) met the primary endpoint. In an inverse probability weighted Cox regression, the LGE–myocardial interface area (hazard ratio [HR]: 1.75; 95% confidence interval [CI]: 1.24 to 2.47; p = 0.001), number of simulated re-entries (HR: 1.40; 95% CI: 1.23 to 1.59; p < 0.01) and LGE volume (HR: 1.44; 95% CI: 1.07 to 1.94; p = 0.02) were associated with arrhythmic events. Computational modeling revealed repolarization heterogeneity and rate-dependent block of electrical wavefronts at the LGE–myocardial interface as putative arrhythmogenic mechanisms directly related to the LGE interface area.ConclusionsThe area of interface between scar and surviving myocardium, as well as simulated re-entrant activity, are associated with an elevated risk of major arrhythmic events in patients with NIDCM and LGE and represent novel risk predictors.

AB - ObjectivesThis study sought to investigate whether shape-based late gadolinium enhancement (LGE) metrics and simulations of re-entrant electrical activity are associated with arrhythmic events in patients with nonischemic dilated cardiomyopathy (NIDCM).BackgroundThe presence of LGE predicts life-threatening ventricular arrhythmias in NIDCM; however, risk stratification remains imprecise. LGE shape and simulations of electrical activity may be able to provide additional prognostic information.MethodsCardiac magnetic resonance (CMR)-LGE shape metrics were computed for a cohort of 156 patients with NIDCM and visible LGE and tested retrospectively for an association with an arrhythmic composite endpoint of sudden cardiac death and ventricular tachycardia. Computational models were created from images and used in conjunction with simulated stimulation protocols to assess the potential for re-entry induction in each patient’s scar morphology. A mechanistic analysis of the simulations was carried out to explain the associations.ResultsDuring a median follow-up of 1,611 (interquartile range: 881 to 2,341) days, 16 patients (10.3%) met the primary endpoint. In an inverse probability weighted Cox regression, the LGE–myocardial interface area (hazard ratio [HR]: 1.75; 95% confidence interval [CI]: 1.24 to 2.47; p = 0.001), number of simulated re-entries (HR: 1.40; 95% CI: 1.23 to 1.59; p < 0.01) and LGE volume (HR: 1.44; 95% CI: 1.07 to 1.94; p = 0.02) were associated with arrhythmic events. Computational modeling revealed repolarization heterogeneity and rate-dependent block of electrical wavefronts at the LGE–myocardial interface as putative arrhythmogenic mechanisms directly related to the LGE interface area.ConclusionsThe area of interface between scar and surviving myocardium, as well as simulated re-entrant activity, are associated with an elevated risk of major arrhythmic events in patients with NIDCM and LGE and represent novel risk predictors.

KW - arrhythmic risk

KW - computational modeling

KW - dilated cardiomyopathy

KW - fibrosis

KW - late gadolinium enhancement

UR - http://www.scopus.com/inward/record.url?scp=85099176353&partnerID=8YFLogxK

U2 - 10.1016/j.jacep.2020.08.036

DO - 10.1016/j.jacep.2020.08.036

M3 - Article

AN - SCOPUS:85099176353

SN - 2405-500X

JO - JACC: Clinical Electrophysiology

JF - JACC: Clinical Electrophysiology

ER -

Late-Gadolinium Enhancement Interface Area and Electrophysiological Simulations Predict Arrhythmic Events in Patients With Nonischemic Dilated Cardiomyopathy

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Keywords

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