Electrophysiological Mechanisms Underlying T-Wave Alternans and Their Role in Arrhythmogenesis

Abstract

T-wave alternans (TWA) reflects every-other-beat alterations in the morphology of the electrocardiogram ST segment or T wave in the setting of a constant heart rate, hence, in the absence of heart rate variability. It is believed to be associated with the dispersion of repolarization and has been used as a non-invasive marker for predicting the risk of malignant cardiac arrhythmias and sudden cardiac death as numerous studies have shown. This review aims to provide up-to-date review on both experimental and simulation studies in elucidating possible mechanisms underlying the genesis of TWA at the cellular level, as well as the genesis of spatially concordant/discordant alternans at the tissue level, and their transition to cardiac arrhythmia. Recent progress and future perspectives in antiarrhythmic therapies associated with TWA are also discussed.

A space-fractional bidomain framework for cardiac electrophysiology: 1D alternans dynamics

“…The alternans dynamics observed in this work is essentially related to the APD restitution properties and to the changes observed in APD restitution as a function of the fractional parameters in the FBD. However, intracellular calcium handling is known to be another important factor of alternans dynamics, independent from APD restitution [3,60]. The Beeler-Reuter cellular description explicitly models intra-cellular calcium, but its dynamics is in essence zerodimensional.…”

“…An illustrative example of action potential and extra-cellular potential profile for the above-mentioned four combinations of fractional exponents is given in Figure A.8 in the Appendix and the particular pairs of conductivities selected (in order to recover the same CV in all cases) are reported in Table A. 3.…”

“…Understanding the complex dynamics underlying the multiscale features of excitable biological media is becoming of paramount importance in cardiac modelling, especially for personalised medical treatment [2,3]. The enormous effort that has been made to this day in theoretical, experimental, and clinical research in cardiac electrophysiology still has not been able to fully elucidate important issues and underlying mechanisms, such as cell-cell communication, emerging behaviors, irregular rhythms (alternans), and arrhythmias onset [4,5].…”

Sudden cardiac death in patients with myocardial infarction: 1.5 primary prevention

“…TWA has been shown to be a risk factor and treatment indicator for patients with post-MI SCD in the Alternans Before Cardioverter Defibrillator (ABCD) trial and Risk Estimation Following Infarction Noninvasive Evaluation (REFINE) trial, and is best performed 10 to 14 weeks after the onset of an MI [51]. Its substrates are associated with repolarization dispersion that is histologically manifested as spatially concordant alternans and spatially discordant alternans, which promotes unidirectional conduction block and leads to reentry [52].…”

Dynamics Study of Constant DI and Constant TR Control for Cardiac Alternans Based on a Two Dimensional Cellular Automata Model

“…Cardiac alternans is a disturbed heart rhythm in which the action potential duration (APD) of cells alternates between long and short values, and manifests on electrocardiograms (ECG) as alternantion in amplitude between two consecutive T-waves [1] . In experimental and clinical practice, cardiac alternans could be a sensitive indicator of arrhthmias leading to life-threatening sudden cardiac death (SCD), which accounts for the death of around 325,000 Americans per year.…”