Myocardial Fibrosis as a Predictor of Sudden Death in Patients With Coronary Artery Disease

Abbasin Zegard, Osita Okafor, Joseph de Bono, Manish Kalla, Mauro Lencioni, Howard Marshall, Lucy Hudsmith, Tian Qiu, Richard Steeds, Berthold Stegemann, Francisco Leyva*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background: The “gray zone” of myocardial fibrosis (GZF) on cardiovascular magnetic resonance may be a substrate for ventricular arrhythmias (VAs). Objectives: The purpose of this study was to determine whether GZF predicts sudden cardiac death (SCD) and VAs (ventricular fibrillation or sustained ventricular tachycardia) in patients with coronary artery disease (CAD) and a wide range of left ventricular ejection fractions (LVEFs). Methods: In this retrospective study of CAD patients, the presence of myocardial fibrosis on visual assessment (MFVA) and GZF mass in patients with MFVA were assessed in relation to SCD and the composite, arrhythmic endpoint of SCD or VAs. Results: Among 979 patients (mean age [± SD]: 65.8 ± 12.3 years), 29 (2.96%) experienced SCD and 80 (8.17%) met the arrhythmic endpoint over median 5.82 years (interquartile range: 4.1 to 7.3 years). In the whole cohort, MFVA was strongly associated with SCD (hazard ratio: 10.1; 95% confidence interval [CI]: 1.42 to 1,278.9) and the arrhythmic endpoint (hazard ratio: 28.0; 95% CI: 4.07 to 3,525.4). In competing risks analyses, associations between LVEF <35% and SCD (subdistribution hazard ratio [sHR]: 2.99; 95% CI: 1.42 to 6.31) and the arrhythmic endpoint (sHR: 4.71; 95% CI: 2.97 to 7.47) were weaker. In competing risk analyses of the MFVA subcohort (n = 832), GZF using the 3SD method (GZF3SD) >5.0 g was strongly associated with SCD (sHR: 10.8; 95% CI: 3.74 to 30.9) and the arrhythmic endpoint (sHR: 7.40; 95% CI: 4.29 to 12.8). Associations between LVEF <35% and SCD (sHR: 2.62; 95% CI: 1.24 to 5.52) and the arrhythmic endpoint (sHR: 4.14; 95% CI: 2.61 to 6.57) were weaker. Conclusions: In CAD patients, MFVA plus quantified GZF3SD mass was more strongly associated with SCD and VAs than LVEF. In selecting patients for implantable cardioverter-defibrillators, assessment of MFVA followed by quantification of GZF3SD mass may be preferable to LVEF.

Original languageEnglish
Pages (from-to)29-41
Number of pages13
JournalJournal of the American College of Cardiology
Issue number1
Early online date4 Jan 2021
Publication statusPublished - 5 Jan 2021

Bibliographical note

Funding Information:
Medtronic provided support for this study in the form of an unrestricted educational grant. Medtronic provided funding for Dr. Zegard’s salary as a research fellow and had no participation in the study. Dr. Leyva has served as a consultant for and has received research funding from Medtronic Inc., Boston Scientific, Abbott, Microport, and Biotronik. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Publisher Copyright:
© 2021 American College of Cardiology Foundation

Copyright 2020 Elsevier B.V., All rights reserved.


  • cardiovascular magnetic resonance
  • gray zone mass
  • implantable cardioverter-defibrillator
  • peri-infarct mass
  • primary prevention
  • ventricular fibrillation
  • ventricular tachycardia


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