The normal physiologic range of QRS complex duration spans between 80 and 125 ms with known differences between females and males which cannot be explained by the anatomical variations of heart sizes. To investigate the reasons for the sex differences as well as for the wide range of normal values, a technology is proposed based on the singular value decomposition and on the separation of different orthogonal components of the QRS complex. This allows classification of the proportions of different components representing the 3-dimensional representation of the electrocardiographic signal as well as classification of components that go beyond the 3-dimensional representation and that correspond to the degree of intricate convolutions of the depolarisation sequence. The technology was applied to 382,019 individual 10-s ECG samples recorded in 639 healthy subjects (311 females and 328 males) aged 33.8 ± 9.4 years. The analyses showed that QRS duration was mainly influenced by the proportions of the first two orthogonal components of the QRS complex. The first component demonstrated statistically significantly larger proportion of the total QRS power (expressed by the absolute area of the complex in all independent ECG leads) in females than in males (64.2 ± 11.6% vs 59.7 ± 11.9%, p < 0.00001-measured at resting heart rate of 60 beats per minute) while the second component demonstrated larger proportion of the QRS power in males compared to females (33.1 ± 11.9% vs 29.6 ± 11.4%, p < 0.001). The analysis also showed that the components attributable to localised depolarisation sequence abnormalities were significantly larger in males compared to females (2.85 ± 1.08% vs 2.42 ± 0.87%, p < 0.00001). In addition to the demonstration of the technology, the study concludes that the detailed convolution of the depolarisation waveform is individual, and that smoother and less intricate depolarisation propagation is the mechanism likely responsible for shorter QRS duration in females.

Department of Internal Medicine and Cardiology Faculty of Medicine University Hospital Brno Masaryk University Jihlavská 20 625 00 Brno Czech Republic

Klinikum Rechts der Isar Technische Universität München Ismaninger Straße 22 81675 Munich Germany

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

Wilhelminenspital der Stadt Wien Montleartstraße 37 1160 Vienna Austria

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Macfarlane PW, Lawrie TDV, et al. The normal electrocardiogram and vectorcardiogram. In: Macfarlane PW, et al., editors. Comprehensive Electrocardiology. London: Springer; 2010.

Rijnbeek PR, et al. Normal values of the electrocardiogram for ages 16–90 years. J. Electrocardiol. 2014;47:914–921. doi: 10.1016/j.jelectrocard.2014.07.022. PubMed DOI

Boineau JP, Spach MS. The relationship between the electrocardiogram and the electrical activity of the heart. J. Electrocardiol. 1968;1:117–124. doi: 10.1016/S0022-0736(68)80014-7. PubMed DOI

Mincholé A, Zacur E, Ariga R, Grau V, Rodriguez B. MRI-based computational torso/biventricular multiscale models to investigate the impact of anatomical variability on the ECG QRS complex. Front. Physiol. 2019;10:1103. doi: 10.3389/fphys.2019.01103. PubMed DOI PMC

Weiss DL, Keller DU, Seemann G, Dössel O. The influence of fibre orientation, extracted from different segments of the human left ventricle, on the activation and repolarization sequence: a simulation study. Europace Suppl. 2007;6:96–104. doi: 10.1093/europace/eum213. PubMed DOI

Mehdirad AA, Nelson SD, Love CJ, Schaal SF, Tchou PJ. QRS duration widening: reduced synchronization of endocardial activation or transseptal conduction time? Pacing Clin. Electrophysiol. 1998;21:1589–1594. doi: 10.1111/j.1540-8159.1998.tb00247.x. PubMed DOI

Carmeliet E. Conduction in cardiac tissue. Historical reflections. Physiol Rep. 2019;7:e13860. doi: 10.14814/phy2.13860. PubMed DOI PMC

Macfarlane PW, McLaughlin SC, Devine B, Yang TF. Effects of age, sex, and race on ECG interval measurements. J. Electrocardiol. 1994;27(Suppl):14–19. doi: 10.1016/S0022-0736(94)80039-1. PubMed DOI

Hnatkova K, Smetana P, Toman O, Schmidt G, Malik M. Sex and race differences in QRS duration. Europace. 2016;18:1842–1849. PubMed

Sia CH, et al. A population-wide study of electrocardiographic (ECG) norms and the effect of demographic and anthropometric factors on selected ECG characteristics in young, Southeast Asian males-results from the Singapore armed forces ECG (SAFE) study. Ann. Noninvasive Electrocardiol. 2019;24:e12634. doi: 10.1111/anec.12634. PubMed DOI PMC

Mohammadi S, et al. Study of the normal heart size in northwest part of Iranian population: a cadaveric study. J. Cardiovasc. Thorac. Res. 2016;8:119–125. doi: 10.15171/jcvtr.2016.25. PubMed DOI PMC

Vanhaebost J, Faouzi M, Mangin P, Michaud K. New reference tables and user-friendly Internet application for predicted heart weights. Int. J. Legal Med. 2014;128:615–620. doi: 10.1007/s00414-013-0958-9. PubMed DOI

Klabunde RE. Cardiovascular Physiology Concepts. Philadelphia: Lippincott; 2012.

Veeraraghavan R, Gourdie RG, Poelzing S. Mechanisms of cardiac conduction: a history of revisions. Am. J. Physiol. Heart Circ. Physiol. 2014;306:H619–H627. doi: 10.1152/ajpheart.00760.2013. PubMed DOI PMC

Mason JW, et al. A fundamental relationship between intraventricular conduction and heart rate. J. Electrocardiol. 2016;49:362–370. doi: 10.1016/j.jelectrocard.2016.03.008. PubMed DOI

Acar B, Köymen H. SVD-based on-line exercise ECG signal orthogonalization. IEEE Trans. Biomed. Eng. 1999;46:311–321. doi: 10.1109/10.748984. PubMed DOI

Ahmed SM, Al-Zoubi Q, Abo-Zahhad M. A hybrid ECG compression algorithm based on singular value decomposition and discrete wavelet transform. J. Med. Eng. Technol. 2007;31:54–61. doi: 10.1080/03091900500518811. PubMed DOI

Kumar R, Kumar A, Singh GK. Hybrid method based on singular value decomposition and embedded zero tree wavelet technique for ECG signal compression. Comput. Methods Programs. Biomed. 2016;129:135–148. doi: 10.1016/j.cmpb.2016.01.006. PubMed DOI

Jung WH, Lee SG. An R-peak detection method that uses an SVD filter and a search back system. Comput. Methods Programs Biomed. 2012;108:1121–1132. doi: 10.1016/j.cmpb.2012.08.002. PubMed DOI

Yana K, Shichiku H, Satoh T, Mizuta H, Ono T. An improved QT interval measurement based on singular value decomposition. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2006;2006:3990–3993. doi: 10.1109/IEMBS.2006.259959. PubMed DOI

Priori SG, et al. Evaluation of the spatial aspects of T-wave complexity in the long-QT syndrome. Circulation. 1997;96:3006–3012. doi: 10.1161/01.CIR.96.9.3006. PubMed DOI

Acar B, Yi G, Hnatkova K, Malik M. Spatial, temporal and wavefront direction characteristics of 12-lead T-wave morphology. Med. Biol. Eng. Comput. 1999;37:574–584. doi: 10.1007/BF02513351. PubMed DOI

Schlegel TT, et al. Accuracy of advanced versus strictly conventional 12-lead ECG for detection and screening of coronary artery disease, left ventricular hypertrophy and left ventricular systolic dysfunction. BMC Cardiovasc. Disord. 2010;10:28. doi: 10.1186/1471-2261-10-28. PubMed DOI PMC

Toman O, et al. Physiologic heart rate dependency of the PQ interval and its sex differences. Sci. Rep. 2020;10:2551. doi: 10.1038/s41598-020-59480-8. PubMed DOI PMC

Guideline ICH. Safety pharmacology studies for human pharmaceuticals S7A. Fed. Regist. 2001;66:36791–36792. PubMed

Guideline ICH. 1E14 Clinical evaluation of QT/QTc interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs. Guidance to industry. Fed. Regist. 2005;70:61134–61135. PubMed

Malik M, et al. Thorough QT/QTc study in patients with advanced Parkinson's disease: cardiac safety of rotigotine. Clin. Pharmacol. Therap. 2008;84:595–603. doi: 10.1038/clpt.2008.143. PubMed DOI

Malik M, et al. Proarrhythmic safety of repeat doses of mirabegron in healthy subjects: a randomized, double-blind, placebo-, and active-controlled thorough QT study. Clin. Pharm. Therap. 2012;92:696–706. doi: 10.1038/clpt.2012.181. PubMed DOI

Perez-Alday EA, et al. Importance of the heart vector origin point definition for an ECG analysis: the Atherosclerosis Risk in Communities (ARIC) study. Comput. Biol. Med. 2019;104:127–138. doi: 10.1016/j.compbiomed.2018.11.013. PubMed DOI PMC

Hnatkova K, et al. Systematic comparisons of electrocardiographic morphology increase the precision of QT interval measurement. Pacing Clin. Electrophysiol. 2009;32:119–130. doi: 10.1111/j.1540-8159.2009.02185.x. PubMed DOI

Malik M, et al. QT dispersion does not represent electrocardiographic interlead heterogeneity of ventricular repolarization. J. Cardiovasc. Electrophysiol. 2000;11:835–843. doi: 10.1111/j.1540-8167.2000.tb00061.x. PubMed DOI

Sur S, Han L, Tereshchenko LG. Comparison of sum absolute QRST integral, and temporal variability in depolarization and repolarization, measured by dynamic vectorcardiography approach, in healthy men and women. PLoS ONE. 2013;8:e57175. doi: 10.1371/journal.pone.0057175. PubMed DOI PMC

Ray D, Hazra S, Goswami DP, Macfarlane PW, Sengupta A. An evaluation of planarity of the spatial QRS loop by three dimensional vectorcardiography: its emergence and loss. J. Electrocardiol. 2017;50:652–660. doi: 10.1016/j.jelectrocard.2017.03.016. PubMed DOI

Jaros R, Martinek R, Danys L. Comparison of different electrocardiography with vectorcardiography transformations. Sensors. 2019;19:3072. doi: 10.3390/s19143072. PubMed DOI PMC

Choudhuri S, Ghosal T, Goswami DP, Sengupta A. Planarity of the spatial QRS loop of vectorcardiogram is a crucial diagnostic and prognostic parameter in acute myocardial infarction. Med Hypotheses. 2019;130:109251. doi: 10.1016/j.mehy.2019.109251. PubMed DOI

Hiraoka M, Kawano S, Sawanobori T, Kokusho S. QRS planarity studies in the vectorcardiogram. Clinical and experimental studies. Jpn. Heart J. 1982;23:39–48. doi: 10.1536/ihj.23.39. PubMed DOI

Arnaud P, Morlet D, Rubel P. Planarity of the spatial QRS loop Comparative analysis in normals, infarcts, ventricular hypertrophies, and intraventricular conduction defects. J. Electrocardiol. 1989;22:143–152. doi: 10.1016/0022-0736(89)90084-8. PubMed DOI

Linde C, et al. Sex differences in cardiac arrhythmia: a consensus document of the European Heart Rhythm Association, endorsed by the Heart Rhythm Society and Asia Pacific Heart Rhythm Society. Europace. 2018;20:1565–1565ao. doi: 10.1093/europace/euy067. PubMed DOI

Ubrich R, et al. (2017) Sex differences in long-term mortality among acute myocardial infarction patients: Results from the ISAR-RISK and ART studies. PLoS ONE. 2017;12:e0186783. doi: 10.1371/journal.pone.0186783. PubMed DOI PMC

Zaman S, Deshmukh T, Aslam A, Martin C, Kovoor P. Sex differences in electrophysiology, ventricular tachyarrhythmia, cardiac arrest and sudden cardiac death following acute myocardial infarction. Heart Lung Circ. 2020;29:1025–1031. doi: 10.1016/j.hlc.2019.07.017. PubMed DOI

Gasparini M, et al. Sex differences in implantable cardiac defibrillator therapy according to arrhythmia detection times. Heart. 2020;106:520–526. doi: 10.1136/heartjnl-2019-315650. PubMed DOI

Johannesen L, et al. Quantitative understanding of QTc prolongation and gender as risk factors for Torsade de Pointes. Clin. Pharmacol. Ther. 2018;103:304–309. doi: 10.1002/cpt.783. PubMed DOI

Andršová I, et al. Individually rate corrected QTc intervals in children and adolescents. Front Physiol. 2019;10:994. doi: 10.3389/fphys.2019.00994. PubMed DOI PMC

Uijen GJ, van Oosterom A. On the detection of the number of signals in multi-lead ECGs. Methods Inf. Med. 1992;31:247–255. doi: 10.1055/s-0038-1634883. PubMed DOI

Uijen GJ, van Oosterom A. The performance of information-theoretic criteria in detecting the number of independent signals in multi-lead ECGs. Methods Inf. Med. 1992;31:256–262. doi: 10.1055/s-0038-1634887. PubMed DOI

Das MK, et al. Fragmented QRS on a 12-lead ECG: A predictor of mortality and cardiac events in patients with coronary artery disease. Heart Rhythm. 2007;4:1385–1392. doi: 10.1016/j.hrthm.2007.06.024. PubMed DOI

Cheema A, et al. Fragmented QRS and mortality risk in patients with left ventricular dysfunction. Circ. Arrhythm Electrophysiol. 2010;3:339–344. doi: 10.1161/CIRCEP.110.940478. PubMed DOI

Pietrasik G, Zareba W. QRS fragmentation: Diagnostic and prognostic significance. Cardiol. J. 2012;19:114–121. doi: 10.5603/CJ.2012.0022. PubMed DOI

Xu S, Yang L, Hong D, Chen L, Wang X. Predictive value of fragmented QRS for ventricular tachyarrhythmias in patients with acute myocardial infarction: a meta-analysis. Eur. J. Clin. Invest. 2020;50:e13182. doi: 10.1111/eci.13182. PubMed DOI

Haukilahti MAE, et al. Gender differences in prevalence and prognostic value of fragmented QRS complex. J. Electrocardiol. 2020;61:1–9. doi: 10.1016/j.jelectrocard.2020.05.010. PubMed DOI

Reichlin T, et al. Automated electrocardiographic quantification of myocardial scar in patients undergoing primary prevention implantable cardioverter-defibrillator implantation: association with mortality and subsequent appropriate and inappropriate therapies. Heart Rhythm. 2020;17:1664–1671. doi: 10.1016/j.hrthm.2020.05.016. PubMed DOI

Zabel M, et al. Analysis of T-wave morphology from the 12-lead electrocardiogram for prediction of long-term prognosis in male US veterans. Circulation. 2002;105:1066–1070. doi: 10.1161/hc0902.104598. PubMed DOI

van Stipdonk AMW, et al. QRS area is a strong determinant of outcome in cardiac resynchronization therapy. Circ. Arrhythm. Electrophysiol. 2018;11:006767. doi: 10.1161/circep.118.006767. PubMed DOI

Emerek K, et al. Vectorcardiographic QRS area is associated with long-term outcome after cardiac resynchronization therapy. Heart Rhythm. 2019;16:213–219. doi: 10.1016/j.hrthm.2018.08.028. PubMed DOI PMC

Malik M, Johannesen L, Hnatkova K, Stockbridge N. Universal correction for QT/RR hysteresis. Drug Saf. 2016;39:577–588. doi: 10.1007/s40264-016-0406-0. PubMed DOI

Gravel H, Jacquemet V, Dahdah N, Curnier D. Clinical applications of QT/RR hysteresis assessment: a systematic review. Ann. Noninvasive Electrocardiol. 2018;23:e12514. doi: 10.1111/anec.12514. PubMed DOI PMC

Hnatkova K, et al. Heart rate correction of the J-to-Tpeak interval. Sci. Rep. 2019;9:15060. doi: 10.1038/s41598-019-51491-4. PubMed DOI PMC

Malik M, et al. Sample size, power calculations, and their implications for the cost of thorough studies of drug induced QT interval prolongation. Pacing Clin. Electrophysiol. 2004;27:1659–1669. doi: 10.1111/j.1540-8159.2004.00701.x. PubMed DOI

Malik M, et al. Importance of QT/RR hysteresis correction in studies of drug-induced QTc interval changes. J. Pharmacokinet. Pharmacodyn. 2018;45:491–503. doi: 10.1007/s10928-018-9587-8. PubMed DOI PMC

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