Fibrosis Entropy Is Associated With Life-Threatening Arrhythmia in Nonischemic Cardiomyopathy

Daniel J. Hammersley; Hassan A. Zaidi; Richard E. Jones; Suzan Hatipoglu; Emmanuel Androulakis; Gabriel Balaban; Lukas Mach; Amrit S. Lota; Zohya Khalique; Antonio De Marvao; Aleksandra Lopuszko; Laura Lazzari; Andrew Ravendren; Ankur Gulati; Resham Baruah; Kaushik Guha; Upasana Tayal; Francisco Leyva; A. John Baksi; James S. Ware; Pablo Lamata; Dudley J. Pennell; Brian P. Halliday; Martin J. Bishop; Sanjay K. Prasad

doi:10.1161/JAHA.124.040517

Fibrosis Entropy Is Associated With Life-Threatening Arrhythmia in Nonischemic Cardiomyopathy

Daniel J. Hammersley
, Hassan A. Zaidi
, Richard E. Jones
, Suzan Hatipoglu
, Emmanuel Androulakis
, Gabriel Balaban
, Lukas Mach
, Amrit S. Lota
, Zohya Khalique
, Antonio De Marvao
, Aleksandra Lopuszko
, Laura Lazzari
, Andrew Ravendren
, Ankur Gulati
, Resham Baruah
, Kaushik Guha
, Upasana Tayal
, Francisco Leyva
, A. John Baksi
, James S. Ware

Pablo Lamata, Dudley J. Pennell, Brian P. Halliday, Martin J. Bishop, Sanjay K. Prasad

Lewisham and Greenwich NHS Trust, London, United Kingdom
Clinical Neurophysiology, Portsmouth Hospitals NHS Trust, United Kingdom

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

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Abstract

BACKGROUND: Greater precision is required for arrhythmic risk stratification of patients with nonischemic cardiomyopathy (NICM). We sought to evaluate whether fibrosis entropy, a measure of scar texture heterogeneity derived from late gadolinium enhancement cardiovascular magnetic resonance, has incremental utility to fibrosis presence for arrhythmic risk prediction in NICM.

METHODS: In this prospective observational cohort study, fibrosis entropy was calculated for patients with NICM and fibrosis (late gadolinium enhancement positive, LGE+), including regions of core fibrosis, gray zone fibrosis and combined core and gray zone fibrosis. Patients with NICM and no fibrosis (LGE-) were included as a comparator group. Adjudicated follow-up for life-threatening arrhythmia included sudden cardiac death, aborted sudden cardiac death, or sustained ventricular tachycardia.

RESULTS: Of 291 patients with LGE+ NICM, 38 (13.1%) experienced life-threatening arrhythmia over a median follow-up of 6.3 years. Core fibrosis entropy (per-SD hazard ratio [HR], 1.77 [95% CI, 1.25-2.52]; P=0.001), gray zone fibrosis entropy (HR, 1.97 [95% CI, 1.20-2.54]; P=0.004), and combined fibrosis entropy (HR, 1.98 [95% CI, 1.30-3.02]; P=0.004) were each associated with life-threatening arrhythmia after adjustment for variables used to determine implantable cardioverter-defibrillator candidacy in clinical practice (left ventricular ejection fraction ≤35% and New York Heart Association class >1) and remained associated after accounting for core and gray zone fibrosis mass. Left ventricular ejection fraction ≤35% was not associated with life-threatening arrhythmia (HR, 1.45 [95% CI, 0.77-2.74]; P=0.250). Integration of fibrosis presence with fibrosis entropy classified patients into low-, intermediate-, and high-arrhythmic-risk groups.

CONCLUSIONS: Deeper phenotypic characterization of scar using fibrosis entropy offers incremental utility to left ventricular ejection fraction and fibrosis presence for arrhythmic risk stratification in NICM.

Original language	English
Article number	e040517
Number of pages	11
Journal	Journal of the American Heart Association
Volume	14
Issue number	18
Early online date	11 Sept 2025
DOIs	https://doi.org/10.1161/JAHA.124.040517
Publication status	Published - 16 Sept 2025

Bibliographical note

Copyright © 2025 The Author(s). Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Funding

This work was supported by: NHLF Royston Centre for Cardiomyopathy grant awarded to S.K.P., D.J.H., R.E.J., U.T., and B.P.H.; The British Heart Foundation (FS/ICRF/21/26019; RE/18/4/34215; SP/17/11/32885); EPSRC 2018/19 DTP—EP/R513064/1 grant; the National Institute for Health Research Biomedical Research Centre at Guy’s and St. Thomas’ Trust and King’s College, the Centre of Excellence in Medical Engineering funded by the Wellcome Trust and Engineering and Physical Sciences; Research Council (EPSRC; WT088641/Z/09/Z); Rosetrees Trust; Alexander Jansons Myocarditis UK Foundation; Royston Centre for Cardiomyopathy Research; Sir Jules Thorn Charitable Trust (21JTA); National Institute for Health Research Royal Brompton Cardiovascular Biomedical Research Unit; National Institute for Health Research Imperial College Biomedical Research Centre; P.L. holds a Wellcome Trust Senior Research Fellowship (209 450/Z/17/Z); H.Z. acknowledges EPSRC 2018/19 DTP-EP/R513064/1 grant; M.J.B., S.K.P., and B.P.H. acknowledge the BHF through project grant PG/22/11159.

Keywords

entropy
Female
Risk Factors
fibrosis
Fibrosis
Arrhythmias, Cardiac - etiology - diagnosis - physiopathology
nonischemic cardiomyopathy
Prospective Studies
Entropy
Male
Aged
Cardiomyopathies - complications - physiopathology - pathology - diagnostic imaging
Magnetic Resonance Imaging, Cine - methods
Myocardium - pathology
Humans
Risk Assessment
arrhythmic risk stratification
Middle Aged

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hammersley-et-al-2025-fibrosis-entropy-is-associated-with-life-threatening-arrhythmia-in-nonischemic-cardiomyopathy
Copyright © 2025 The Author(s). Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Final published version, 670 KBLicence: CC BY-NC 4.0

Cite this

Hammersley, D. J., Zaidi, H. A., Jones, R. E., Hatipoglu, S., Androulakis, E., Balaban, G., Mach, L., Lota, A. S., Khalique, Z., De Marvao, A., Lopuszko, A., Lazzari, L., Ravendren, A., Gulati, A., Baruah, R., Guha, K., Tayal, U., Leyva, F., Baksi, A. J., ... Prasad, S. K. (2025). Fibrosis Entropy Is Associated With Life-Threatening Arrhythmia in Nonischemic Cardiomyopathy. Journal of the American Heart Association, 14(18), Article e040517. https://doi.org/10.1161/JAHA.124.040517

@article{57be158e6f6a4ab2b530bf864aa1a89c,

title = "Fibrosis Entropy Is Associated With Life-Threatening Arrhythmia in Nonischemic Cardiomyopathy",

abstract = "BACKGROUND: Greater precision is required for arrhythmic risk stratification of patients with nonischemic cardiomyopathy (NICM). We sought to evaluate whether fibrosis entropy, a measure of scar texture heterogeneity derived from late gadolinium enhancement cardiovascular magnetic resonance, has incremental utility to fibrosis presence for arrhythmic risk prediction in NICM.METHODS: In this prospective observational cohort study, fibrosis entropy was calculated for patients with NICM and fibrosis (late gadolinium enhancement positive, LGE+), including regions of core fibrosis, gray zone fibrosis and combined core and gray zone fibrosis. Patients with NICM and no fibrosis (LGE-) were included as a comparator group. Adjudicated follow-up for life-threatening arrhythmia included sudden cardiac death, aborted sudden cardiac death, or sustained ventricular tachycardia.RESULTS: Of 291 patients with LGE+ NICM, 38 (13.1\%) experienced life-threatening arrhythmia over a median follow-up of 6.3 years. Core fibrosis entropy (per-SD hazard ratio [HR], 1.77 [95\% CI, 1.25-2.52]; P=0.001), gray zone fibrosis entropy (HR, 1.97 [95\% CI, 1.20-2.54]; P=0.004), and combined fibrosis entropy (HR, 1.98 [95\% CI, 1.30-3.02]; P=0.004) were each associated with life-threatening arrhythmia after adjustment for variables used to determine implantable cardioverter-defibrillator candidacy in clinical practice (left ventricular ejection fraction ≤35\% and New York Heart Association class >1) and remained associated after accounting for core and gray zone fibrosis mass. Left ventricular ejection fraction ≤35\% was not associated with life-threatening arrhythmia (HR, 1.45 [95\% CI, 0.77-2.74]; P=0.250). Integration of fibrosis presence with fibrosis entropy classified patients into low-, intermediate-, and high-arrhythmic-risk groups. CONCLUSIONS: Deeper phenotypic characterization of scar using fibrosis entropy offers incremental utility to left ventricular ejection fraction and fibrosis presence for arrhythmic risk stratification in NICM.",

keywords = "entropy, Female, Risk Factors, fibrosis, Fibrosis, Arrhythmias, Cardiac - etiology - diagnosis - physiopathology, nonischemic cardiomyopathy, Prospective Studies, Entropy, Male, Aged, Cardiomyopathies - complications - physiopathology - pathology - diagnostic imaging, Magnetic Resonance Imaging, Cine - methods, Myocardium - pathology, Humans, Risk Assessment, arrhythmic risk stratification, Middle Aged",

author = "Hammersley, \{Daniel J.\} and Zaidi, \{Hassan A.\} and Jones, \{Richard E.\} and Suzan Hatipoglu and Emmanuel Androulakis and Gabriel Balaban and Lukas Mach and Lota, \{Amrit S.\} and Zohya Khalique and \{De Marvao\}, Antonio and Aleksandra Lopuszko and Laura Lazzari and Andrew Ravendren and Ankur Gulati and Resham Baruah and Kaushik Guha and Upasana Tayal and Francisco Leyva and Baksi, \{A. John\} and Ware, \{James S.\} and Pablo Lamata and Pennell, \{Dudley J.\} and Halliday, \{Brian P.\} and Bishop, \{Martin J.\} and Prasad, \{Sanjay K.\}",

note = "Copyright {\textcopyright} 2025 The Author(s). Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.",

year = "2025",

month = sep,

day = "16",

doi = "10.1161/JAHA.124.040517",

language = "English",

volume = "14",

journal = "Journal of the American Heart Association",

issn = "2047-9980",

publisher = "Wiley-Blackwell",

number = "18",

}

Hammersley, DJ, Zaidi, HA, Jones, RE, Hatipoglu, S, Androulakis, E, Balaban, G, Mach, L, Lota, AS, Khalique, Z, De Marvao, A, Lopuszko, A, Lazzari, L, Ravendren, A, Gulati, A, Baruah, R, Guha, K, Tayal, U, Leyva, F, Baksi, AJ, Ware, JS, Lamata, P, Pennell, DJ, Halliday, BP, Bishop, MJ & Prasad, SK 2025, 'Fibrosis Entropy Is Associated With Life-Threatening Arrhythmia in Nonischemic Cardiomyopathy', Journal of the American Heart Association, vol. 14, no. 18, e040517. https://doi.org/10.1161/JAHA.124.040517

TY - JOUR

T1 - Fibrosis Entropy Is Associated With Life-Threatening Arrhythmia in Nonischemic Cardiomyopathy

AU - Hammersley, Daniel J.

AU - Zaidi, Hassan A.

AU - Jones, Richard E.

AU - Hatipoglu, Suzan

AU - Androulakis, Emmanuel

AU - Balaban, Gabriel

AU - Mach, Lukas

AU - Lota, Amrit S.

AU - Khalique, Zohya

AU - De Marvao, Antonio

AU - Lopuszko, Aleksandra

AU - Lazzari, Laura

AU - Ravendren, Andrew

AU - Gulati, Ankur

AU - Baruah, Resham

AU - Guha, Kaushik

AU - Tayal, Upasana

AU - Leyva, Francisco

AU - Baksi, A. John

AU - Ware, James S.

AU - Lamata, Pablo

AU - Pennell, Dudley J.

AU - Halliday, Brian P.

AU - Bishop, Martin J.

AU - Prasad, Sanjay K.

N1 - Copyright © 2025 The Author(s). Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

PY - 2025/9/16

Y1 - 2025/9/16

N2 - BACKGROUND: Greater precision is required for arrhythmic risk stratification of patients with nonischemic cardiomyopathy (NICM). We sought to evaluate whether fibrosis entropy, a measure of scar texture heterogeneity derived from late gadolinium enhancement cardiovascular magnetic resonance, has incremental utility to fibrosis presence for arrhythmic risk prediction in NICM.METHODS: In this prospective observational cohort study, fibrosis entropy was calculated for patients with NICM and fibrosis (late gadolinium enhancement positive, LGE+), including regions of core fibrosis, gray zone fibrosis and combined core and gray zone fibrosis. Patients with NICM and no fibrosis (LGE-) were included as a comparator group. Adjudicated follow-up for life-threatening arrhythmia included sudden cardiac death, aborted sudden cardiac death, or sustained ventricular tachycardia.RESULTS: Of 291 patients with LGE+ NICM, 38 (13.1%) experienced life-threatening arrhythmia over a median follow-up of 6.3 years. Core fibrosis entropy (per-SD hazard ratio [HR], 1.77 [95% CI, 1.25-2.52]; P=0.001), gray zone fibrosis entropy (HR, 1.97 [95% CI, 1.20-2.54]; P=0.004), and combined fibrosis entropy (HR, 1.98 [95% CI, 1.30-3.02]; P=0.004) were each associated with life-threatening arrhythmia after adjustment for variables used to determine implantable cardioverter-defibrillator candidacy in clinical practice (left ventricular ejection fraction ≤35% and New York Heart Association class >1) and remained associated after accounting for core and gray zone fibrosis mass. Left ventricular ejection fraction ≤35% was not associated with life-threatening arrhythmia (HR, 1.45 [95% CI, 0.77-2.74]; P=0.250). Integration of fibrosis presence with fibrosis entropy classified patients into low-, intermediate-, and high-arrhythmic-risk groups. CONCLUSIONS: Deeper phenotypic characterization of scar using fibrosis entropy offers incremental utility to left ventricular ejection fraction and fibrosis presence for arrhythmic risk stratification in NICM.

AB - BACKGROUND: Greater precision is required for arrhythmic risk stratification of patients with nonischemic cardiomyopathy (NICM). We sought to evaluate whether fibrosis entropy, a measure of scar texture heterogeneity derived from late gadolinium enhancement cardiovascular magnetic resonance, has incremental utility to fibrosis presence for arrhythmic risk prediction in NICM.METHODS: In this prospective observational cohort study, fibrosis entropy was calculated for patients with NICM and fibrosis (late gadolinium enhancement positive, LGE+), including regions of core fibrosis, gray zone fibrosis and combined core and gray zone fibrosis. Patients with NICM and no fibrosis (LGE-) were included as a comparator group. Adjudicated follow-up for life-threatening arrhythmia included sudden cardiac death, aborted sudden cardiac death, or sustained ventricular tachycardia.RESULTS: Of 291 patients with LGE+ NICM, 38 (13.1%) experienced life-threatening arrhythmia over a median follow-up of 6.3 years. Core fibrosis entropy (per-SD hazard ratio [HR], 1.77 [95% CI, 1.25-2.52]; P=0.001), gray zone fibrosis entropy (HR, 1.97 [95% CI, 1.20-2.54]; P=0.004), and combined fibrosis entropy (HR, 1.98 [95% CI, 1.30-3.02]; P=0.004) were each associated with life-threatening arrhythmia after adjustment for variables used to determine implantable cardioverter-defibrillator candidacy in clinical practice (left ventricular ejection fraction ≤35% and New York Heart Association class >1) and remained associated after accounting for core and gray zone fibrosis mass. Left ventricular ejection fraction ≤35% was not associated with life-threatening arrhythmia (HR, 1.45 [95% CI, 0.77-2.74]; P=0.250). Integration of fibrosis presence with fibrosis entropy classified patients into low-, intermediate-, and high-arrhythmic-risk groups. CONCLUSIONS: Deeper phenotypic characterization of scar using fibrosis entropy offers incremental utility to left ventricular ejection fraction and fibrosis presence for arrhythmic risk stratification in NICM.

KW - entropy

KW - Female

KW - Risk Factors

KW - fibrosis

KW - Fibrosis

KW - Arrhythmias, Cardiac - etiology - diagnosis - physiopathology

KW - nonischemic cardiomyopathy

KW - Prospective Studies

KW - Entropy

KW - Male

KW - Aged

KW - Cardiomyopathies - complications - physiopathology - pathology - diagnostic imaging

KW - Magnetic Resonance Imaging, Cine - methods

KW - Myocardium - pathology

KW - Humans

KW - Risk Assessment

KW - arrhythmic risk stratification

KW - Middle Aged

UR - https://www.ahajournals.org/doi/10.1161/JAHA.124.040517

UR - https://www.scopus.com/pages/publications/105016624962

U2 - 10.1161/JAHA.124.040517

DO - 10.1161/JAHA.124.040517

M3 - Article

C2 - 40932094

SN - 2047-9980

VL - 14

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

IS - 18

M1 - e040517

ER -

Fibrosis Entropy Is Associated With Life-Threatening Arrhythmia in Nonischemic Cardiomyopathy

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