Control of rapid heart rate changes for electrocardiographic analysis: implications for thorough QT studies

Extramiana, Fabrice; Maison‐Blanche, Pierre; Haggui, Abdeddayem; Badilini, Fabio; Beaufils, Philippe; Leenhardt, Antoine

doi:10.1002/clc.20

Cited by 17 publications

(14 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In agreement with our data, Yuan et al reported that the effect of dofetilide on in situ human monophasic APD90 is not rate-dependent (Yuan, Wohlfart, Rasmussen, Olsson, & Blomstrom-Lundqvist, 1994). In contrast, other studies reported that drug-induced prolongation of ventricular repolarization with dofetilide, sotalol and moxifloxacin was more pronounced with slow pacing rates (Extramiana et al, 2006; Funck-Brentano et al, 1991; Lande et al, 1988; Okada, Ogawa, Sadanaga, & Mitamura, 1996). Therefore, drug action as a function of pacing rate in the human heart warrants further assessment.…”

Section: Discussionmentioning

confidence: 88%

Human ex-vivo action potential model for pro-arrhythmia risk assessment

Page

Ratchada

Miron

et al. 2016

Journal of Pharmacological and Toxicological Methods

View full text Add to dashboard Cite

While current S7B/E14 guidelines have succeeded in protecting patients from QT-prolonging drugs, the absence of a predictive paradigm identifying pro-arrhythmic risks has limited the development of valuable drug programs. We investigated if a human ex-vivo action potential (AP)-based model could provide a more predictive approach for assessing pro-arrhythmic risk in man. Human ventricular trabeculae from ethically consented organ donors were used to evaluate the effects of dofetilide, d,l-sotalol, quinidine, paracetamol and verapamil on AP duration (APD) and recognized pro-arrhythmia predictors (short-term variability of APD at 90% repolarization (STV(APD90)), triangulation (ADP90-APD30) and incidence of early afterdepolarizations at 1 and 2 Hz to quantitatively identify the pro-arrhythmic risk. Each drug was blinded and tested separately with 3 concentrations in triplicate trabeculae from 5 hearts, with one vehicle time control per heart. Electrophysiological stability of the model was not affected by sequential applications of vehicle (0.1% dimethyl sulfoxide). Paracetamol and verapamil did not significantly alter anyone of the AP parameters and were classified as devoid of pro-arrhythmic risk. Dofetilide, d,l-sotalol and quinidine exhibited an increase in the manifestation of pro-arrhythmia markers. The model provided quantitative and actionable activity flags and the relatively low total variability in tissue response allowed for the identification of pro-arrhythmic signals. Power analysis indicated that a total of 6 trabeculae derived from 2 hearts are sufficient to identify drug-induced pro-arrhythmia. Thus, the human ex-vivo AP-based model provides an integrative translational assay assisting in shaping clinical development plans that could be used in conjunction with the new CiPA-proposed approach.

show abstract

Section: Discussionmentioning

confidence: 88%

Human ex-vivo action potential model for pro-arrhythmia risk assessment

Page

Ratchada

Miron

et al. 2016

Journal of Pharmacological and Toxicological Methods

View full text Add to dashboard Cite

show abstract

“…The power of such investigations will be substantially increased (and thus the necessary study size decreased) if the combined individual-specific corrections for both heart rate and hysteresis are used. Correcting QT interval individually for both rate and hysteresis appears clearly preferable to preselecting ECG data in which the effect of QT/RR hysteresis is considered unimportant because of heart rate stability (8).…”

Section: Discussionmentioning

confidence: 99%

Subject-specific profiles of QT/RR hysteresis

Malik¹,

Hnatkova²,

Novotný³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

The time lag of the QT interval adaptation to heart rate changes (QT/RR hysteresis) was studied in 40 healthy subjects (18 females; mean age, 30.4 Ϯ 8.1 yr) with 3 separate daytime (Ͼ13 h) 12-lead electrocardiograms (ECG) in each subject. In each recording, 330 individual 10-s ECG segments were measured, including 100 segments preceded by 2 min of heart rate varying greater than Ϯ2 beats/min. Other segments were preceded by a stable heart rate. In segments preceded by variable rate, QT/RR hysteresis was characterized by parameters of the exponential decay models. The intrasubject SDs of values were compared with the intersubject SD of the individual means. The values were also correlated to individually optimized parameters of heart rate correction. Intrasubject SDs of were substantially smaller than the population SD of individual means (0.390 Ϯ 0.197 vs. 0.711, P Ͻ 0.0001). The values were unrelated to the QT/RR correction parameters. When compared with the corrected QT (QTc) for averaged RR intervals in 10-s ECGs and with the averaged RR intervals in 2-min history, QTc for QT/RR hysteresis led to a substantially smaller SD of QTc values (11.4 Ϯ 2.00, 6.33 Ϯ 1.31, and 4.66 Ϯ 0.85 ms, respectively, P Ͻ 0.0001). Thus the speed with which the QT interval adapts to heart rate changes is highly individual with intrasubject stability and intersubject variability. QT/RR hysteresis is independent of the static QT/RR relationship and should be considered as a separate physiological process. The combination of individual heart rate correction with individual hysteresis correction of the QT interval is likely to lead to substantial improvements of cardiac repolarization studies.QT adaptation; individual QT correction; electrocardiogram measurement; corrected QT variability HEART RATE DEPENDENCY of the electrocardiographic QT interval has been the subject of numerous studies. Electrocardiographic data sets of variable sizes, sources, and quality have been used to investigate the relationship of the QT interval to heart rate (3,12,14,26,28), most frequently with the aim of finding a universally applicable heart rate correction formula. On the contrary, the adaptation of QT interval duration to rapid rate changes, which is the lag with which QT interval duration responds to heart rate changes, has been studied much less frequently. Indeed, in numerous studies that investigated the relationship between QT interval and heart rate in short-term (such as 10 s) electrocardiograms (ECG), the QT adaptation to heart rate changes has been, as a rule, impossible since no heart rate history preceding the measured ECGs was available.The time scale of the adaptation of QT interval to heart rate changes, most frequently termed the QT/RR hysteresis, has been previously approximated in investigations with constant pacing rates. Such experiments measured both the action potential durations (11) and QT intervals in surface ECGs (17). Studies of QT/RR hysteresis in long-term ECG recordings without pacing provocation appeared only recently, ma...

show abstract

“…27 Figure 4 shows that, when applying our stability filter, the percentage of rejected beats was correlated with the HR variability parameter PNN50. For instance, a noise filter can be set to reject noisy QRS-T complexes and the minimal number of QRS-T complexes defining a template may also be selected to improve the signal-to-noise ratio.…”

Section: Qt Durationmentioning

confidence: 96%

ECG Evaluation of Ventricular Properties: The Importance of Cardiac Cycle Length

Extramiana¹,

Leenhardt²,

Maison‐Blanche³

2009

Noninvasive Electrocardiol

Self Cite

View full text Add to dashboard Cite

Ventricular repolarization properties are dependent on cardiac cycle length. The aim of this article is to emphasize the importance of taking into account heart rate influences on QT duration but also on current and future T-wave morphology parameters. The relationship between QT interval duration and RR interval is a fundamental property of the myocardium that is impaired by the presence of channelopathies such as the LQTS or SQTS, but also by the presence of a cardiomyopathy. Assessing this property is also important when the individual QT/RR relationship is used for individual QT correction in the setting of evaluation of drugs' effect on QT duration. T-wave descriptors such as the relative weight of the terminal part of the T-wave, the amplitude of T-wave apex and Principal Component Analysis parameters are also dependent on heart rate. Assessing ventricular repolarisation ECG parameters at different heart rates avoids the need for difficult rate-correction and helps to better understand and characterize ventricular repolarisation properties.

show abstract

Control of rapid heart rate changes for electrocardiographic analysis: implications for thorough QT studies

Cited by 17 publications

References 25 publications

Human ex-vivo action potential model for pro-arrhythmia risk assessment

Human ex-vivo action potential model for pro-arrhythmia risk assessment

Subject-specific profiles of QT/RR hysteresis

ECG Evaluation of Ventricular Properties: The Importance of Cardiac Cycle Length

Contact Info

Product

Resources

About