Background: Increased beat-to-beat variability in cardiac repolarization time is a tentative risk marker of drug-induced torsades de pointes. We developed a new, automatic method based on the temporal variability of the T-wave down slope to assess this variability.
Method And Results: Leads V(1) to V(6) of resting electrocardiograms were recorded in 42 healthy subjects (18-68 years, 22 men). The temporal variability at 50% of the T-wave down slope, deltaT50 (1.5 ± 0.41 milliseconds; range, 0.86-2.66 milliseconds), was measured with an accuracy of 1 millisecond on at least 9 pairs of electrocardiogram complexes with a signal-to-noise ratio more than 10 and changes in the R-R interval less than 150 milliseconds. The correlation between repeated measurements of deltaT50 was high. DeltaT50 was measured without corrections for age, sex, heart rate, T-wave amplitude, signal-to-noise ratio, R-R variability, and QTcF because none of these factors explained more than 4% of the within-subject deltaT50 variability.
Conclusion: The beat-to-beat repolarization variability was measured with high fidelity with the deltaT50 method and was a robust measure in healthy volunteers.
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http://dx.doi.org/10.1016/j.jelectrocard.2011.04.010 | DOI Listing |
Cardiovasc Endocrinol Metab
March 2025
Department of Cardiology, G B Pant Institute of Postgraduate Medical Education and Research, New Delhi, India.
The impact of obesity on heart rate variability (HRV) and ventricular repolarization, both vital indicators of cardiovascular health, is the focus of this review. Obesity, measured by BMI, waist circumference, and waist-to-hip ratio, significantly increases cardiovascular disease (CVD) risk due to structural and autonomic heart changes. Findings show that obese individuals exhibit prolonged QT and Tpeak-to-Tend (Tpe) intervals, suggesting delayed ventricular recovery and greater arrhythmia risk.
View Article and Find Full Text PDFHeart Rhythm
January 2025
Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, MD, USA. Electronic address:
Background: Spontaneously occurring life threatening reentrant arrhythmias result when a propagating premature beat encounters a region with significant dispersion of refractoriness. Although localized structural tissue heterogeneities and prescribed cell functional gradients have been incorporated into computational electrophysiological models, a quantitative framework for the evolution from normal to abnormal behavior that occurs via disease is lacking.
Objective: The purpose of this study was to develop a probabilistic modeling framework that represents the complex interplay of cell function and tissue structure in health and disease which predicts the emergence of premature beats and the initiation of reentry.
JCI Insight
January 2025
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, United States of America.
The hERG1 potassium channel conducts the cardiac repolarizing current, IKr. hERG1 has emerged as a therapeutic target for cardiac diseases marked by prolonged actional potential duration (APD). Unfortunately, many hERG1 activators display off-target and proarrhythmic effects that limit their therapeutic potential.
View Article and Find Full Text PDFBiomolecules
December 2024
Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, Splaiul Independentei 91-95, 050095 Bucharest, Romania.
Cenobamate is a novel third-generation antiepileptic drug used for the treatment of focal onset seizures and particularly for multi-drug-resistant epilepsy; it acts on multiple targets: GABA receptors (EC 42-194 µM) and persistent neuronal Na currents (IC 59 µM). Side effects include QT interval shortening with >20 ms, but not <300 ms. Our in vitro cardiac safety pharmacology study was performed via whole-cell patch-clamp on HEK293T cells with persistent/inducible expression of human cardiac ion channel isoforms hNav1.
View Article and Find Full Text PDFJ Electrocardiol
December 2024
Physiology Unit, Department of Pre-Clinical Sciences, Faculty of Medical Sciences, The University of the West Indies, St. Augustine Campus, Mount Hope Hospital, Building 35, Uriah Butler Highway, Trinidad and Tobago.
Background: The aim of this simulation was to examine the utility of a novel ECG-based index of cardiac action potential (AP) triangulation, the Tstart-to-Tpeak (TsTp) interval-to-JTstart (JTs) interval ratio, for assessment of changes in AP profile imposed through variations in the duration of the plateau phase and the phase 3 repolarization.
Methods: ECGs were simulated using a realistic rabbit model based on experimental data. The AP plateau was measured at APD30, and the phase 3 was assessed as APD90-to-APD30 difference (AP durations at 90 % and 30 % repolarization, respectively).
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