The T-peak–T-end Interval as a Marker of Repolarization Abnormality: A Comparison with the QT Interval for Five Different Drugs

Bhuiyan, Tanveer Ahmed; Graff, Claus; Kanters, Jørgen K.; Nielsen, Jimmi; Melgaard, Jacob; Matz, Jørgen; Toft, Egon; Struijk, Johannes

doi:10.1007/s40261-015-0328-0

Cited by 14 publications

(9 citation statements)

References 32 publications

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“…A lack of positive association between repolarization duration and repolarization heterogeneity has not previously been shown for ac- (Bhuiyan et al, 2015). While these were small but precise studies focusing on the effects of specific ion channel blocking agents, the etiology of repolarization prolongation in our study is undoubtedly variable involving an unknown mixture of ion channel and ion concentration derangements.…”

Section: Discussioncontrasting

confidence: 55%

Is myocardial repolarization duration associated with repolarization heterogeneity?

Marill

Dorsey

Holmes

et al. 2017

Noninvasive Electrocardiol

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Section: Discussioncontrasting

confidence: 55%

Is myocardial repolarization duration associated with repolarization heterogeneity?

Marill

Dorsey

Holmes

et al. 2017

Noninvasive Electrocardiol

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“…Accordingly, pure hERG/iKr current blocking drugs prolong both the J-T peak and the T peak -T end intervals, while J-T peak tends to be shortened by multichannel blocking drugs [23]. However, declaring T peak as cutting point between early and late repolarization is questionable [24], and there is no generally accepted physiologic reason for choosing the T peak to subdivide the repolarization interval for assessment of pro-arrhythmic effects [25]. It has recently been challenged whether a lack of J-T peak prolongation can reliably differentiate between safe and proarrhythmic QT end prolongation [26].…”

Section: Discussionmentioning

confidence: 99%

T vector velocity: A new ECG biomarker for identifying drug effects on cardiac ventricular repolarization

Bystricky

Maier

Gintant

et al. 2018

Preprint

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16We present a new family TrX of ECG biomarkers based on the T vector velocity (TVV) for assessing 17 drug effects on ventricular repolarization. Assuming a link between the TVV and the instantaneous 18 change of the cellular action potentials, drugs accelerating repolarization by blocking inward 19 (depolarizing) ion currents cause a relative increase of the TVV, while drugs delaying repolarization by 20 blocking outward ion currents cause a relative decrease of the TVV. 21 Evaluating the published data from two FDA funded studies, the TrX effect profiles indicate 22 increasingly delayed electrical activity over the entire repolarization process for drugs solely reducing 23 outward potassium current (dofetilide, moxifloxacin). For drugs eliciting block of the inward sodium or 24 calcium currents (mexiletine, lidocaine), the TrX effect profiles were consistent with accelerated 25 electrical activity in the initial repolarization phase. For multichannel blocking drugs (ranolazine) or 26 drug combinations blocking multiple ion currents (dofetilide + mexiletine, dofetilide + lidocaine), the 27 overall TrX effect profiles indicate a superposition of the individual TrX effect profiles. 28 The parameter Tr40c allows separating pure potassium channel blocking drugs from multichannel 29 blocking drugs with an area under the ROC curve (AUC) value of 0.90, CI = [0.88 to 0.92]. This is 30 significantly larger than the performance of J-T peak c (0.81, CI = [0.78 to 0.84]) using the published data 31 from the second FDA study. Further performance improvement was achieved by combining the ten 32 parameters Tr10c to Tr100c in a logistic regression model, resulting in an AUC value of 0.94. 33 The TVV based approach substantially improves assessment of drug effects on cardiac repolarization, 34 providing a plausible and improved mechanistic link between drug effects on ionic currents and overall 35 ventricular repolarization reflected in the body surface ECG. TVV may contribute to a better 36 assessment of the proarrhythmic risk of drugs beyond QTc prolongation and JT peak c. 37 3 38

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“…However, it should be noted that one study found no significant differences between the application of Fridericia's and Johannesen's correction coefficients (Zareba et al., 2017). The duration of TpTe is closely related to that of the QTcF interval and has been shown to increase proportionately with QTcF when looking at drug‐induced abnormal repolarization (Bhuiyan et al., 2015). It has also previously been shown that TpTe itself is not necessarily predictive of mortality (Smetana et al., 2011).…”

Section: Discussionmentioning

confidence: 99%

Comparing the consistency of electrocardiogram interval measurements by resting ECG versus 12‐lead Holter

Mendzelevski¹,

Spencer

Freier

et al. 2021

Noninvasive Electrocardiol

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Twelve-lead electrocardiogram (ECG) recordings are a standard and readily available method used to assess patient cardiac health and detect cardiac abnormalities. Their use is ubiquitous in clinical practice and in most clinical trials, where a standard 10-s 12lead ECG is considered an essential component to determine the physiological effect of an investigational medicinal product (IMP) (ICH E14, 2005).To accurately assess the effect of a drug on the QT/QTc interval and determine whether an IMP causes QT prolongation, and by extension increased risk for cardiac arrhythmia and sudden death (Roden, 2004), the QT/QTc interval changes are closely monitored at predetermined predose and postdose timepoints during clinical

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The T-peak–T-end Interval as a Marker of Repolarization Abnormality: A Comparison with the QT Interval for Five Different Drugs

Abstract: The duration of the QT interval and TpTe are closely related. Drugs appear to prolong the TpTe interval as a predictable fraction of the total QT prolongation.

Cited by 14 publications

References 32 publications

Is myocardial repolarization duration associated with repolarization heterogeneity?

Is myocardial repolarization duration associated with repolarization heterogeneity?

T vector velocity: A new ECG biomarker for identifying drug effects on cardiac ventricular repolarization

Comparing the consistency of electrocardiogram interval measurements by resting ECG versus 12‐lead Holter

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