Unmasking atrial repolarization to assess alternans, spatiotemporal heterogeneity, and susceptibility to atrial fibrillation

Eleclazine, a new selective cardiac late sodium current inhibitor, confers concurrent protection against autonomically induced atrial premature beats, repolarization alternans and heterogeneity, and atrial fibrillation in an intact porcine model

“…6 Consistent with this finding is our observation in the intact animals that the PT a interval, which correlates with atrial APD (r ¼ 0.94), 11 is significantly shortened, with parallel shortening of the ventricular repolarization duration measure QT interval ( Figure 3). These findings are in agreement with those of Qi et al, 24 who demonstrated the presence of late I Na in the left and right atria as well as ventricles using whole-cell patch clamp techniques.…”

“…5 This compound binds to the cardiac sodium channels with rapid kinetics, reducing cardiac late I Na with minimal influences on other cardiac ion channels including peak I Na , I Cal , I Ks , and I Kr . 6 We used a new model 7 that incorporates the influence of both divisions of the autonomic nervous system, prompted by clinical and experimental evidence of the highly arrhythmogenic nature of coactivation of vagal and sympathetic neural inputs, [8][9][10] and makes use of a novel technique for atrial T-wave morphology monitoring 11 for the assessment of repolarization alternans [12][13][14] and heterogeneity. 14 …”

Alternans in atria: Mechanisms and clinical relevance

“…This notion is supported experimentally by the demonstration that ventricular fibrillation is always preceded by discordant AP alternans [102]. Similarly to findings in ventricle, discordant alternans was also observed in atria and has been directly linked to the development of atrial fibrillation [7,12,96]. The underlying mechanisms for the formation of spatially discordant alternans remain uncertain and most likely are determined by the combination of factors that are discussed below.…”

“…The clinical use of atrial AP repolarization alternans as a diagnostic tool, however, is hindered by the fact that the atrial repolarization signal is masked in the conventional ECG recordings by the ventricular QRS complex and therefore the clinical exploitation of the relationship between atrial alter-nans and the development of atrial arrhythmias for risk assessment has been limited. However, recently progress has been made in several experimental [12,90,96] and clinical studies [7,8,11,97,98] using monophasic AP electrodes to monitor atrial repolarization alternans in vivo. These and other studies involving computer simulations [99], animal models [12,90,96,100] and studies in humans [7,8,11,97,98] have provided convincing evidence that AP alternans in atria may lead directly to AF (Fig.…”

Atrial fibrillation: Can electrograms be interpreted without repolarization information?

“…Into this field comes the timely work of Verrier et al, 11 who set out to detect atrial repolarization from standard electrograms in order to determine AF susceptibility. Using standard clinical catheters, the authors recorded atrial repolarization (T a ) waves in anesthetized pigs and studied the impact of vagus nerve stimulation and of atrial ischemia or acetylcholine plus epinephrine on AF inducibility.…”