The electrocardiographic (ECG) assessment of the T peak-T end (Tpe) intervals has been used in many clinical studies, but several related physiological aspects have not been reported. Specifically, the sources of the Tpe differences between different ECG leads have not been systematically researched, the relationship of Tpe duration to underlying heart rate has not been firmly established, and little is known about the mutual correspondence of Tpe intervals measured in different ECG leads. This study evaluated 796,620 10-s 12-lead ECGs obtained from long-term Holters recorded in 639 healthy subjects (311 female) aged 33.8 ± 9.4 years. For each ECG, transformation to orthogonal XYZ lead was used to measure Tpe in the orthogonal vector magnitude (used as a reference for lead-to-lead comparisons) and to construct a three-dimensional T wave loop. The loop roundness was expressed by a ratio between its circumference and length. These ratios were significantly related to the standard deviation of Tpe durations in different ECG leads. At the underlying heart rate of 60 beats per minute, Tpe intervals were shorter in female than in male individuals (82.5 ± 5.6 vs 90.0 ± 6.5 ms, p < 0.0001). When studying linear slopes between Tpe intervals measured in different leads and the underlying heart rate, we found only minimal heart rate dependency, which was not systematic across the ECG leads and/or across the population. For any ECG lead, positive Tpe/RR slope was found in some subjects (e.g., 79 and 25% of subjects for V2 and V4 measurements, respectively) and a negative Tpe/RR slope in other subjects (e.g., 40 and 65% for V6 and V5, respectively). The steepest positive and negative Tpe/RR slopes were found for measurements in lead V2 and V4, respectively. In all leads, the Tpe/RR slope values were close to zero, indicating, on average, Tpe changes well below 2 ms for RR interval changes of 100 ms. On average, longest Tpe intervals were measured in lead V2, the shortest in lead III. The study concludes that the Tpe intervals measured in different leads cannot be combined. Irrespective of the measured ECG lead, the Tpe interval is not systematically heart rate dependent, and no heart rate correction should be used in clinical Tpe investigations.

Department of Internal Medicine and Cardiology University Hospital Brno Faculty of Medicine Masaryk University Brno Czechia

Klinikum rechts der Isar Technische Universität München Munich Germany

National Heart and Lung Institute Imperial College London London United Kingdom

Wilhelminenspital der Stadt Wien Vienna Austria

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Acar B., Köymen H. (1999). SVD-based on-line exercise ECG signal orthogonalization. PubMed DOI

Acar B., Yi G., Hnatkova K., Malik M. (1999). Spatial, temporal and wavefront direction characteristics of 12-lead T-wave morphology. PubMed DOI

Antzelevitch C. (2008). Drug-induced spatial dispersion of repolarization. PubMed PMC

Antzelevitch C., Di Diego J. M. (2019). Tpeak-Tend interval as a marker of arrhythmic risk. PubMed DOI PMC

Batchvarov V., Hnatkova K., Malik M. (2002). Assessment of noise in digital electrocardiograms. PubMed DOI

Böhm M., Schumacher H., Teo K. K., Lonn E. M., Mahfoud F., Ukena C., et al. (2020). Resting heart rate and cardiovascular outcomes in diabetic and non-diabetic individuals at high cardiovascular risk analysis from the ONTARGET/TRANSCEND trials. PubMed DOI

Chua K. C., Rusinaru C., Reinier K., Uy-Evanado A., Chugh H., Gunson K., et al. (2016). Tpeak-to-Tend interval corrected for heart rate: a more precise measure of increased sudden death risk? PubMed DOI PMC

Copie X., Hnatkova K., Staunton A., Fei L., Camm A. J., Malik M. (1996). Predictive power of increased heart rate versus depressed left ventricular ejection fraction and heart rate variability for risk stratification after myocardial infarction. Results of a two-year follow-up study. PubMed DOI

Damen A. A., van der Kam J. (1982). The use of the singular value decomposition in electrocardiography. PubMed DOI

Day C. P., McComb L. M., Campbell R. W. F. (1990). QT dispersion: an indication of arrhythmia risk in patients with long QT intervals. PubMed DOI PMC

Edenbrandt L., Pahlm O. (1988). Vectorcardiogram synthesized from a 12-lead ECG: superiority of the inverse Dower matrix. PubMed DOI

El-Sherif N., Myerburg R. J., Scherlag B. J., Befeler B., Aranda J. M., Castellanos A., et al. (1976). Electrocardiographic antecedents of primary ventricular fibrillation. Value of the R-on-T phenomenon in myocardial infarction. PubMed DOI PMC

Fenichel R. R., Malik M., Antzelevitch C., Sanguinetti M., Roden D. M., Priori S. G., et al. (2004). Drug-induced Torsades de Pointes and implications for drug development. PubMed PMC

Garnett C. E., Zhu H., Malik M., Fossa A. A., Zhang J., Badilini F., et al. (2012). Methodologies to characterize the QT/corrected QT interval in the presence of drug-induced heart rate changes or other autonomic effects. PubMed DOI

Gravel H., Jacquemet V., Dahdah N., Curnier D. (2018). Clinical applications of QT/RR hysteresis assessment: a systematic review. PubMed DOI PMC

Guideline I. C. H. (2001). Safety pharmacology studies for human pharmaceuticals S7A. PubMed

Guldenring D., Finlay D. D., Strauss D. G., Galeotti L., Nugent C. D., Donnelly M. P., et al. (2012). Transformation of the Mason-Likar 12-lead electrocardiogram to the Frank vectorcardiogram. PubMed

Halámek J., Jurák P., Bunch T. J., Lipoldová J., Novák M., Vondra V., et al. (2010). Use of a novel transfer function to reduce repolarization interval hysteresis. PubMed DOI

Hasan M. A., Abbott D., Baumert M. (2012). Beat-to-beat vectorcardiographic analysis of ventricular depolarization and repolarization in myocardial infarction. PubMed DOI PMC

Hnatkova K., Smetana P., Toman O., Bauer A., Schmidt G., Malik M. (2009). Systematic comparisons of electrocardiographic morphology increase the precision of QT interval measurement. PubMed DOI

Hnatkova K., Vicente J., Johannesen L., Garnett C., Strauss D. G., Stockbridge N., et al. (2019a). Detection of T wave peak for serial comparisons of JTp interval. PubMed DOI PMC

Hnatkova K., Vicente J., Johannesen L., Garnett C., Strauss D. G., Stockbridge N., et al. (2019b). Heart rate correction of the J-to-Tpeak interval. PubMed DOI PMC

Huang H. C., Lin L. Y., Yu H. Y., Ho Y. L. (2009). Risk stratification by T-wave morphology for cardiovascular mortality in patients with systolic heart failure. PubMed DOI

Johannesen L., Vicente J., Hosseini M., Strauss D. G. (2016). Automated algorithm for J-Tpeak and Tpeak-Tend assessment of drug-induced proarrhythmia risk. PubMed DOI PMC

Johannesen L., Vicente J., Mason J. W., Sanabria C., Waite-Labott K., Hong M., et al. (2014). Differentiating drug-induced multichannel block on the electrocardiogram: randomized study of dofetilide, quinidine, ranolazine, and verapamil. PubMed DOI

Kors J. A., van Herpen G. (1998). Measurement error as a source of QT dispersion: a computerised analysis. PubMed DOI PMC

Kors J. A., van Herpen G., Sittig A. C., van Bemmel J. H. (1990). Reconstruction of the Frank vectorcardiogram from standard electrocardiographic leads: diagnostic comparison of different methods. PubMed DOI

Kors J. A., van Herpen G., van Bemmel J. H. (1999). QT dispersion. PubMed

Malik M. (2004). Errors and misconceptions in ECG measurement used for the detection of drug induced QT interval prolongation. PubMed DOI

Malik M., Acar B., Gang Y., Yap Y. G., Hnatkova K., Camm A. J. (2000). QT dispersion does not represent electrocardiographic interlead heterogeneity of ventricular repolarization. PubMed DOI

Malik M., Andreas J.-O., Hnatkova K., Hoeckendorff J., Cawello W., Middle M., et al. (2008a). Thorough QT/QTc study in patients with advanced Parkinson’s disease: cardiac safety of rotigotine. PubMed DOI

Malik M., Batchvarov V. N. (2000). Measurement, interpretation, and clinical potential of QT dispersion. PubMed DOI

Malik M., Camm A. J. (1997). Mystery of QTc interval dispersion. PubMed

Malik M., Hnatkova K., Kowalski D., Keirns J. J., van Gelderen E. M. Q. T. (2013). /RR curvatures in healthy subjects: sex differences and covariates. PubMed PMC

Malik M., Hnatkova K., Novotny T., Schmidt G. (2008b). Subject-specific profiles of QT/RR hysteresis. PubMed

Malik M., Huikuri H., Lombardi F., Schmidt G., Zabel M. (2018). Conundrum of the Tpeak-Tend interval. PubMed DOI

Malik M., Johannesen L., Hnatkova K., Stockbridge N. (2016). Universal correction for QT/RR hysteresis. PubMed DOI

Malik M., van Gelderen E. M., Lee J. H., Kowalski D. L., Yen M., Goldwater R., et al. (2012). Proarrhythmic safety of repeat doses of mirabegron in healthy subjects: a randomized, double-blind, placebo-, and active-controlled thorough QT study. PubMed DOI

Mozos I., Filimon L. (2013). QT and Tpeak-Tend intervals in shift workers. PubMed DOI

Okin P. M., Devereux R. B., Howard B. V., Fabsitz R. R., Lee E. T., Welty T. K. (2000). Assessment of QT interval and QT dispersion for prediction of all-cause and cardiovascular mortality in American Indians. The Strong Heart Study. PubMed DOI

Rautaharju P. M. (1999). QT and dispersion of ventricular repolarization: the greatest fallacy in electrocardiography in the 1990s. PubMed

Rautaharju P. M. (2002). Why did QT dispersion die? PubMed

Seegers J., Hnatkova K., Friede T., Malik M., Zabel M. (2017). T-wave loop area from a pre-implant 12-lead ECG is associated with appropriate ICD shocks. PubMed DOI PMC

Shenthar J., Deora S., Rai M., Nanjappa Manjunath C. (2015). Prolonged Tpeak-end and Tpeak-end/QT ratio as predictors of malignant ventricular arrhythmias in the acute phase of ST-segment elevation myocardial infarction: a prospective case-control study. PubMed DOI

Sicouri S., Antzelevitch C. (1991). A subpopulation of cells with unique electrophysiological properties in the deep subepicardium of the canine ventricle. The M cell. PubMed DOI

Smetana P., Schmidt A., Zabel M., Hnatkova K., Franz M., Huber K., et al. (2011). Assessment of repolarization heterogeneity for prediction of mortality in cardiovascular disease: peak to the end of the T wave interval and nondipolar repolarization components. PubMed DOI

Toman O., Hnatkova K., Smetana P., Huster K. M., Šišáková M., Barthel P., et al. (2020). Physiologic heart rate dependency of the PQ interval and its sex differences. PubMed DOI PMC

Tse G., Gong M., Wong W. T., Georgopoulos S., Letsas K. P., Vassiliou V. S., et al. (2017). The Tpeak - Tend interval as an electrocardiographic risk marker of arrhythmic and mortality outcomes: a systematic review and meta-analysis. PubMed

Vicente J., Hosseini M., Johannesen L., Strauss D. G. (2017). Electrocardiographic biomarkers to confirm drug’s electrophysiological effects used for proarrhythmic risk prediction under CiPA. PubMed DOI

Xue J. Q. (2009). Robust QT interval estimation - from algorithm to validation. PubMed PMC

Yu Z., Chen Z., Wu Y., Chen R., Li M., Chen X., et al. (2018). Electrocardiographic parameters effectively predict ventricular tachycardia/fibrillation in acute phase and abnormal cardiac function in chronic phase of ST-segment elevation myocardial infarction. PubMed DOI

Zareba W. (2006). Genotype-specific ECG patterns in long QT syndrome. PubMed

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