Mechanism Linking T-Wave Alternans to the Genesis of Cardiac Fibrillation

Abstract

Background-Although T-wave alternans has been closely associated with vulnerability to ventricular arrhythmias, the cellular processes underlying T-wave alternans and their role, if any, in the mechanism of reentry remain unclear. Methods and Results-T-wave alternans on the surface ECG was elicited in 8 Langendorff-perfused guinea pig hearts during fixed-rate pacing while action potentials were recorded simultaneously from 128 epicardial sites with voltage-sensitive dyes. Alternans of the repolarization phase of the action potential was observed above a critical threshold heart rate (HR) (209Ϯ46 bpm) that was significantly lower (by 57Ϯ36 bpm) than the HR threshold for alternation of action potential depolarization. The magnitude (range, 2.7 to 47.0 mV) and HR threshold (range, 171 to 272 bpm) of repolarization alternans varied substantially between cells across the epicardial surface. T-wave alternans on the surface ECG was explained primarily by beat-to-beat alternation in the time course of cellular repolarization. Above a critical HR, membrane repolarization alternated with the opposite phase between neighboring cells (ie, discordant alternans), creating large spatial gradients of repolarization. In the presence of discordant alternans, a small acceleration of pacing cycle length produced a characteristic sequence of events: (1) unidirectional block of an impulse propagating against steep gradients of repolarization, (2) reentrant propagation, and (3) the initiation of ventricular fibrillation. Conclusions-Repolarization alternans at the level of the single cell accounts for T-wave alternans on the surface ECG.Discordant alternans produces spatial gradients of repolarization of sufficient magnitude to cause unidirectional block and reentrant ventricular fibrillation. These data establish a mechanism linking T-wave alternans of the ECG to the pathogenesis of sudden cardiac death. (Circulation. 1999;99:1385-1394.)

Mechanisms for Discordant Alternans

“…The number of nodes seen depended partially on tissue length. Although only single nodes have been observed experimentally, 8 this study predicts that more may be found if larger tissues are studied. Simulations also successfully replicated the experimental observation of faster pacing converting concordant to discordant alternans.…”

“…Alternatively, conduction block occurring every other beat resulting in alternating conduction patterns and alternating size of excited tissue also could produce TWA. 7 A recent optical mapping study by Pastore et al 8 elegantly demonstrated a relationship between discordant alternans associated with TWA and arrhythmia induction. Discordant alternans is the phenomenon of two spatially distinct regions exhibiting APD alternans of opposite phases.…”

“…As such, it has the potential to produce larger alternans of the ECG T wave than concordant alternans. In the study by Pastore et al, 8 several mechanisms for discordant alternans were speculated upon. The purpose of the current study is to present a mechanism for discordant alternans initiation and stabilization using ion channel models and nonlinear dynamics theory.…”

Regional increase of extracellular potassium leads to electrical instability and reentry occurrence through the spatial heterogeneity of APD restitution

“…AP alternans in amplitude and duration are frequently observed at the onset of ischemia (21,45) and during rapid pacing (15,48). It was demonstrated that elevation of [K ϩ ] o can also cause AP alternans (19,38).…”

Control of Electrical Alternans in Canine Cardiac Purkinje Fibers

“…Because heart cells are refractory to further stimulation during an action potential, alternans of APD results in an alternans of refractoriness, the magnitude of which may vary across different regions of the heart. Several studies have shown that the resulting spatial dispersion of refractoriness facilitates the development of local conduction block [2][3][4][5], which may in turn cause the normally planar wave of electrical excitation in cardiac tissue to break and form spiral waves [6]. If the spiral waves also encounter regions of disparate refractoriness, they may disintegrate into multiple wavelets, which may account for the onset of the lethal heart rhythm disorder ventricular fibrillation [7][8][9].…”