Arrhythmic Risk Stratification by Cardiovascular Magnetic Resonance Imaging in Patients With Nonischemic Cardiomyopathy

Daniel J. Hammersley; Abbasin Zegard; Emmanuel Androulakis; Richard E. Jones; Osita Okafor; Suzan Hatipoglu; Lukas Mach; Amrit S. Lota; Zohya Khalique; Antonio de Marvao; Ankur Gulati; Resham Baruah; Kaushik Guha; James S. Ware; Upasana Tayal; Dudley J. Pennell; Brian P. Halliday; Tian Qiu; Sanjay K. Prasad; Francisco Leyva

doi:10.1016/j.jacc.2024.06.046

Arrhythmic Risk Stratification by Cardiovascular Magnetic Resonance Imaging in Patients With Nonischemic Cardiomyopathy

Daniel J. Hammersley, Abbasin Zegard, Emmanuel Androulakis, Richard E. Jones, Osita Okafor, Suzan Hatipoglu, Lukas Mach, Amrit S. Lota, Zohya Khalique, Antonio de Marvao, Ankur Gulati, Resham Baruah, Kaushik Guha, James S. Ware, Upasana Tayal, Dudley J. Pennell, Brian P. Halliday, Tian Qiu, Sanjay K. Prasad, Francisco Leyva^*

^*Corresponding author for this work

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

17 Citations (SciVal)

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Abstract

BACKGROUND: Myocardial fibrosis (MF) forms part of the arrhythmic substrate for ventricular arrhythmias (VAs).

OBJECTIVES: This study sought to determine whether total myocardial fibrosis (TF) and gray zone fibrosis (GZF), assessed using cardiovascular magnetic resonance, are better than left ventricular ejection fraction (LVEF) in predicting ventricular arrhythmias in patients with nonischemic cardiomyopathy (NICM).

METHODS: Patients with NICM in a derivation cohort (n = 866) and a validation cohort (n = 848) underwent quantification of TF and GZF. The primary composite endpoint was sudden cardiac death or VAs (ventricular fibrillation or ventricular tachycardia).

RESULTS: The primary endpoint was met by 52 of 866 (6.0%) patients in the derivation cohort (median follow-up: 7.5 years; Q1-Q3: 5.2-9.3 years). In competing-risks analyses, MF on visual assessment (MF VA) predicted the primary endpoint (HR: 5.83; 95% CI: 3.15-10.8). Quantified MF measures permitted categorization into 3 risk groups: a TF of >0 g and ≤10 g was associated with an intermediate risk (HR: 4.03; 95% CI: 1.99-8.16), and a TF of >10 g was associated with the highest risk (HR: 9.17; 95% CI: 4.64-18.1) compared to patients with no MF VA (lowest risk). Similar trends were observed in the validation cohort. Categorization into these 3 risk groups was achievable using TF or GZF in combination or in isolation. In contrast, LVEF of <35% was a poor predictor of the primary endpoint (validation cohort HR: 1.99; 95% CI: 0.99-4.01).

CONCLUSIONS: MF VA is a strong predictor of sudden cardiac death and VAs in NICM. TF and GZF mass added incremental value to MF VA. In contrast, LVEF was a poor discriminator of arrhythmic risk.

Original language	English
Pages (from-to)	1407-1420
Number of pages	14
Journal	Journal of the American College of Cardiology
Volume	84
Issue number	15
Early online date	30 Aug 2024
DOIs	https://doi.org/10.1016/j.jacc.2024.06.046
Publication status	Published - 8 Oct 2024

Bibliographical note

Crown Copyright © 2024. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/).

Funding

This work was supported by a National Heart and Lung Institute Foundation grant awarded to Drs Prasad, Hammersley, Jones, Tayal, and Halliday as well as a British Society for Heart Failure Research Fellowship and a British Heart Foundation Clinical Research Training Fellowship (FS/CRTF/23/24444) awarded to Dr Mach. Additionally, the study was supported by Rosetrees Trust, the Alexander Jansons Myocarditis UK Foundation, a BHF Intermediate Clinical Research Fellowship awarded to Dr Halliday (FS/ICRF/21/26019), and an MRC Fellowship awarded to Dr Tayal (MRC MR/W023830/1). This work was additionally supported by The British Heart Foundation (RE/18/4/ 34215; SP/17/11/32885), Royston Centre for Cardiomyopathy Research, Sir Jules Thorn Charitable Trust (21JTA), Medical Research Council (UK), National Institute for Health Research, Royal Brompton Cardiovascular Biomedical Research Unit, and National Institute for Health Research Imperial College Biomedical Research Centre. Medtronic Plc provided funding for the salary as a research fellow for Dr Zegard. Boston Scientific provided funding for Dr Qiu (statistician). These companies had no participation whatsoever in the study. The views expressed in this work are those of the authors and not necessarily those of the funders. Dr Hammersley has received research funding from Siemens. Dr Baruah is an employee of Astra-Zeneca. Dr Guha has received honoraria from Bayer, Pfizer, Novartis, AstraZeneca, and Servier Laboratories; has received an unrestricted educational grant from Biotronik; and has received travel assistance from Abbott Laboratories, Medtronic, Biotronik, and Boston Scientific. Dr Ware has acted as a consultant for MyoKardia, Foresite Labs, Pfizer, and Health Lumen. Dr Halliday has received honoraria from AstraZeneca. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Funders	Funder number
Royal Brompton and Harefield Cardiovascular Research Centre

Keywords

arrythmia
fibrosis
nonischemic cardiomyopathy
risk stratification
sudden cardiac death

Access to Document

10.1016/j.jacc.2024.06.046Licence: CC BY 4.0

DJ Hammersley et al_Arrhythmic Risk Stratification by Cardiovascular MRI in Patients w Nonischemic Cardiomyopathy
Crown Copyright © 2024. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/).
Final published version, 2.14 MBLicence: CC BY 4.0

Cite this

Hammersley, D. J., Zegard, A., Androulakis, E., Jones, R. E., Okafor, O., Hatipoglu, S., Mach, L., Lota, A. S., Khalique, Z., de Marvao, A., Gulati, A., Baruah, R., Guha, K., Ware, J. S., Tayal, U., Pennell, D. J., Halliday, B. P., Qiu, T., Prasad, S. K., & Leyva, F. (2024). Arrhythmic Risk Stratification by Cardiovascular Magnetic Resonance Imaging in Patients With Nonischemic Cardiomyopathy. Journal of the American College of Cardiology, 84(15), 1407-1420. https://doi.org/10.1016/j.jacc.2024.06.046

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title = "Arrhythmic Risk Stratification by Cardiovascular Magnetic Resonance Imaging in Patients With Nonischemic Cardiomyopathy",

abstract = "BACKGROUND: Myocardial fibrosis (MF) forms part of the arrhythmic substrate for ventricular arrhythmias (VAs).OBJECTIVES: This study sought to determine whether total myocardial fibrosis (TF) and gray zone fibrosis (GZF), assessed using cardiovascular magnetic resonance, are better than left ventricular ejection fraction (LVEF) in predicting ventricular arrhythmias in patients with nonischemic cardiomyopathy (NICM).METHODS: Patients with NICM in a derivation cohort (n = 866) and a validation cohort (n = 848) underwent quantification of TF and GZF. The primary composite endpoint was sudden cardiac death or VAs (ventricular fibrillation or ventricular tachycardia).RESULTS: The primary endpoint was met by 52 of 866 (6.0%) patients in the derivation cohort (median follow-up: 7.5 years; Q1-Q3: 5.2-9.3 years). In competing-risks analyses, MF on visual assessment (MF VA) predicted the primary endpoint (HR: 5.83; 95% CI: 3.15-10.8). Quantified MF measures permitted categorization into 3 risk groups: a TF of >0 g and ≤10 g was associated with an intermediate risk (HR: 4.03; 95% CI: 1.99-8.16), and a TF of >10 g was associated with the highest risk (HR: 9.17; 95% CI: 4.64-18.1) compared to patients with no MF VA (lowest risk). Similar trends were observed in the validation cohort. Categorization into these 3 risk groups was achievable using TF or GZF in combination or in isolation. In contrast, LVEF of <35% was a poor predictor of the primary endpoint (validation cohort HR: 1.99; 95% CI: 0.99-4.01). CONCLUSIONS: MF VA is a strong predictor of sudden cardiac death and VAs in NICM. TF and GZF mass added incremental value to MF VA. In contrast, LVEF was a poor discriminator of arrhythmic risk. ",

keywords = "arrythmia, fibrosis, nonischemic cardiomyopathy, risk stratification, sudden cardiac death",

author = "Hammersley, {Daniel J.} and Abbasin Zegard and Emmanuel Androulakis and Jones, {Richard E.} and Osita Okafor and Suzan Hatipoglu and Lukas Mach and Lota, {Amrit S.} and Zohya Khalique and {de Marvao}, Antonio and Ankur Gulati and Resham Baruah and Kaushik Guha and Ware, {James S.} and Upasana Tayal and Pennell, {Dudley J.} and Halliday, {Brian P.} and Tian Qiu and Prasad, {Sanjay K.} and Francisco Leyva",

note = "Crown Copyright {\textcopyright} 2024. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/).",

year = "2024",

month = oct,

day = "8",

doi = "10.1016/j.jacc.2024.06.046",

language = "English",

volume = "84",

pages = "1407--1420",

journal = "Journal of the American College of Cardiology",

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Hammersley, DJ, Zegard, A, Androulakis, E, Jones, RE, Okafor, O, Hatipoglu, S, Mach, L, Lota, AS, Khalique, Z, de Marvao, A, Gulati, A, Baruah, R, Guha, K, Ware, JS, Tayal, U, Pennell, DJ, Halliday, BP, Qiu, T, Prasad, SK & Leyva, F 2024, 'Arrhythmic Risk Stratification by Cardiovascular Magnetic Resonance Imaging in Patients With Nonischemic Cardiomyopathy', Journal of the American College of Cardiology, vol. 84, no. 15, pp. 1407-1420. https://doi.org/10.1016/j.jacc.2024.06.046

TY - JOUR

T1 - Arrhythmic Risk Stratification by Cardiovascular Magnetic Resonance Imaging in Patients With Nonischemic Cardiomyopathy

AU - Hammersley, Daniel J.

AU - Zegard, Abbasin

AU - Androulakis, Emmanuel

AU - Jones, Richard E.

AU - Okafor, Osita

AU - Hatipoglu, Suzan

AU - Mach, Lukas

AU - Lota, Amrit S.

AU - Khalique, Zohya

AU - de Marvao, Antonio

AU - Gulati, Ankur

AU - Baruah, Resham

AU - Guha, Kaushik

AU - Ware, James S.

AU - Tayal, Upasana

AU - Pennell, Dudley J.

AU - Halliday, Brian P.

AU - Qiu, Tian

AU - Prasad, Sanjay K.

AU - Leyva, Francisco

N1 - Crown Copyright © 2024. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/).

PY - 2024/10/8

Y1 - 2024/10/8

N2 - BACKGROUND: Myocardial fibrosis (MF) forms part of the arrhythmic substrate for ventricular arrhythmias (VAs).OBJECTIVES: This study sought to determine whether total myocardial fibrosis (TF) and gray zone fibrosis (GZF), assessed using cardiovascular magnetic resonance, are better than left ventricular ejection fraction (LVEF) in predicting ventricular arrhythmias in patients with nonischemic cardiomyopathy (NICM).METHODS: Patients with NICM in a derivation cohort (n = 866) and a validation cohort (n = 848) underwent quantification of TF and GZF. The primary composite endpoint was sudden cardiac death or VAs (ventricular fibrillation or ventricular tachycardia).RESULTS: The primary endpoint was met by 52 of 866 (6.0%) patients in the derivation cohort (median follow-up: 7.5 years; Q1-Q3: 5.2-9.3 years). In competing-risks analyses, MF on visual assessment (MF VA) predicted the primary endpoint (HR: 5.83; 95% CI: 3.15-10.8). Quantified MF measures permitted categorization into 3 risk groups: a TF of >0 g and ≤10 g was associated with an intermediate risk (HR: 4.03; 95% CI: 1.99-8.16), and a TF of >10 g was associated with the highest risk (HR: 9.17; 95% CI: 4.64-18.1) compared to patients with no MF VA (lowest risk). Similar trends were observed in the validation cohort. Categorization into these 3 risk groups was achievable using TF or GZF in combination or in isolation. In contrast, LVEF of <35% was a poor predictor of the primary endpoint (validation cohort HR: 1.99; 95% CI: 0.99-4.01). CONCLUSIONS: MF VA is a strong predictor of sudden cardiac death and VAs in NICM. TF and GZF mass added incremental value to MF VA. In contrast, LVEF was a poor discriminator of arrhythmic risk.

AB - BACKGROUND: Myocardial fibrosis (MF) forms part of the arrhythmic substrate for ventricular arrhythmias (VAs).OBJECTIVES: This study sought to determine whether total myocardial fibrosis (TF) and gray zone fibrosis (GZF), assessed using cardiovascular magnetic resonance, are better than left ventricular ejection fraction (LVEF) in predicting ventricular arrhythmias in patients with nonischemic cardiomyopathy (NICM).METHODS: Patients with NICM in a derivation cohort (n = 866) and a validation cohort (n = 848) underwent quantification of TF and GZF. The primary composite endpoint was sudden cardiac death or VAs (ventricular fibrillation or ventricular tachycardia).RESULTS: The primary endpoint was met by 52 of 866 (6.0%) patients in the derivation cohort (median follow-up: 7.5 years; Q1-Q3: 5.2-9.3 years). In competing-risks analyses, MF on visual assessment (MF VA) predicted the primary endpoint (HR: 5.83; 95% CI: 3.15-10.8). Quantified MF measures permitted categorization into 3 risk groups: a TF of >0 g and ≤10 g was associated with an intermediate risk (HR: 4.03; 95% CI: 1.99-8.16), and a TF of >10 g was associated with the highest risk (HR: 9.17; 95% CI: 4.64-18.1) compared to patients with no MF VA (lowest risk). Similar trends were observed in the validation cohort. Categorization into these 3 risk groups was achievable using TF or GZF in combination or in isolation. In contrast, LVEF of <35% was a poor predictor of the primary endpoint (validation cohort HR: 1.99; 95% CI: 0.99-4.01). CONCLUSIONS: MF VA is a strong predictor of sudden cardiac death and VAs in NICM. TF and GZF mass added incremental value to MF VA. In contrast, LVEF was a poor discriminator of arrhythmic risk.

KW - arrythmia

KW - fibrosis

KW - nonischemic cardiomyopathy

KW - risk stratification

KW - sudden cardiac death

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DO - 10.1016/j.jacc.2024.06.046

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