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.

Department of Cardiology and Pneumology University Medical Center Göttingen Germany

Department of Cardiology Inselspital Bern University Hospital Bern Switzerland

Department of Cardiology University Hospital of Basel Basel Switzerland

Department of Cardiovascular Sciences University of Leuven Leuven Belgium

Department of Internal Medicine and Cardiology Masaryk University Brno Czech Republic

Department of Internal Medicine and Cardiology University Hospital Brno Brno Czech Republic

Department of Medical Physiology University Medical Center Utrecht Utrecht The Netherlands

Department of Medical Statistics University Medical Center Göttingen Göttingen Germany

German Center for Cardiovascular Research Partner Site Munich Heart Alliance Munich Germany

German Center of Cardiovascular Research Partner Site Göttingen Göttingen Germany

Klinikum rechts der Isar Technical University of Munich Munich Germany

Medical Research Center Oulu University Central Hospital of Oulu and University of Oulu Oulu Finland

National Heart and Lung Institute Imperial College ICTEM Hammersmith Campus 72 Du Cane Road Shepherd's Bush London W12 0NN UK

Research Department of Epidemiology and Public Health University College London UK

University Hospital for Internal Medicine 3 Medical University Innsbruck Innsbruck Austria

Veteran Affairs and Georgetown University Medical Centers Washington DC USA

Comment In

Eur Heart J. 2022 Oct 21;43(40):4192-4194. doi: 10.1093/eurheartj/ehac198. PubMed

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