University of Oulu

Katerina Hnatkova and others, QRS micro-fragmentation as a mortality predictor, European Heart Journal, Volume 43, Issue 40, 21 October 2022, Pages 4177–4191,

QRS micro-fragmentation as a mortality predictor

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Author: Hnatkova, Katerina1; Andršová, Irena2,3; Novotný, Tomáš2,2;
Organizations: 1National Heart and Lung Institute, Imperial College, ICTEM, Hammersmith Campus, 72 Du Cane Road, Shepherd’s Bush, London W12 0NN, UK
2Department of Internal Medicine and Cardiology, University Hospital Brno, Brno, Czech Republic
3Department of Internal Medicine and Cardiology, Masaryk University, Brno, Czech Republic
4Research Department of Epidemiology and Public Health, University College London, UK
5Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium
6Department of Medical Physiology, University Medical Center Utrecht, Utrecht, The Netherlands
7Medical Research Center Oulu, University Central Hospital of Oulu and University of Oulu, Oulu, Finland
8Department of Cardiology, Inselspital, Bern University Hospital, Bern, Switzerland
9Department of Cardiology and Pneumology, University Medical Center, Göttingen, Germany
10German Center of Cardiovascular Research (DZHK), Partner Site Göttingen, Göttingen, Germany
11Department of Medical Statistics, University Medical Center Göttingen, Göttingen, Germany
12University Hospital for Internal Medicine III, Medical University Innsbruck, Innsbruck, Austria
13Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
14German Center for Cardiovascular Research Partner Site Munich Heart Alliance, Munich, Germany
15Veteran Affairs and Georgetown University Medical Centers, Washington, DC, USA
16Department of Cardiology, University Hospital of Basel, Basel, Switzerland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.7 MB)
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Language: English
Published: Oxford University Press, 2022
Publish Date: 2023-06-09


Aims: Fragmented QRS complex with visible notching on standard 12-lead electrocardiogram (ECG) is understood to represent depolarization abnormalities and to signify risk of cardiac events. Depolarization abnormalities with similar prognostic implications likely exist beyond visual recognition but no technology is presently suitable for quantification of such invisible ECG abnormalities. We present such a technology.

Methods and results: A signal processing method projects all ECG leads of the QRS complex into optimized three perpendicular dimensions, reconstructs the ECG back from this three-dimensional projection, and quantifies the difference (QRS ‘micro’-fragmentation, QRS-μf) between the original and reconstructed signals. QRS ‘micro’-fragmentation was assessed in three different populations: cardiac patients with automatic implantable cardioverter-defibrillators, cardiac patients with severe abnormalities, and general public. The predictive value of QRS-μf for mortality was investigated both univariably and in multivariable comparisons with other risk factors including visible QRS ‘macro’-fragmentation, QRS-Mf. The analysis was made in a total of 7779 subjects of whom 504 have not survived the first 5 years of follow-up. In all three populations, QRS-μf was strongly predictive of survival (P < 0.001 univariably, and P < 0.001 to P = 0.024 in multivariable regression analyses). A similar strong association with outcome was found when dichotomizing QRS-μf prospectively at 3.5%. When QRS-μf was used in multivariable analyses, QRS-Mf and QRS duration lost their predictive value.

Conclusion: In three populations with different clinical characteristics, QRS-μf was a powerful mortality risk factor independent of several previously established risk indices. Electrophysiologic abnormalities that contribute to increased QRS-μf values are likely responsible for the predictive power of visible QRS-Mf.

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Series: European heart journal
ISSN: 0195-668X
ISSN-E: 1522-9645
ISSN-L: 0195-668X
Volume: 43
Issue: 40
Pages: 4177 - 4191
DOI: 10.1093/eurheartj/ehac085
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: The EU-CERT-ICD study was funded by the European Community’s 7th Framework Programme (HEALTH-F2-2009-602299). The ECG analyses were supported in part by British Heart Foundation (NH/16/2/32499).
EU Grant Number: (602299) EU-CERT-ICD - Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators in EUrope
Copyright information: © The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.