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Background— The genesis of the electrocardiographic T wave is incompletely understood and subject to controversy. We have correlated the ventricular repolarization sequence with simultaneously recorded T waves. Methods and Results— Nine pig hearts were Langendorff-perfused (atrial pacing, cycle length 650 ms). Local activation and repolarization times were derived from unipolar electrograms sampling the ventricular myocardium. Dispersion of repolarization time was determined along 4 anatomic axes: left ventricle (LV)–right ventricle (RV), LV:apico-basal, LV:anterior-posterior, and LV:transmural. The heart was immersed in a fluid-filled bucket containing 61 electrodes to determine T p (T peak in lead of maximum integral), T p T e (T p to T end ), and T p T e _total (first T peak in any lead to last T end in any lead). Repolarization was nonlinearly distributed in time. RT 25 (time at which 25% of sites were repolarized, 288±26 ms) concurred with T p . T p T e was 38±8 ms, and T p T e _total was 75±9 ms. T p T e _total correlated with dispersion of repolarization time in the entire heart (73±18 ms), but not with dispersion of repolarization times along individual axes (LV–RV, 66±17 ms; LV:apico-basal, 51±18 ms; LV:anterior-posterior, 51±27 ms; mean LV:transmural, 14±7 ms; all n=9). Conclusions— We provide a correlation between local repolarization and T wave in a pseudo-ECG. Repolarization differences along all anatomic axes contribute to the T wave. T p T e _total represents total dispersion of repolarization. At T p , ≈25% of ventricular sites have been repolarized.

We present results from a study in which endocardial and epicardial activation sequences, both for ventricular stimulated and for atrioventricular-conducted activation, were reconstructed from (pseudo) body surface potentials. The study consists of 2 parts. In part I, transmural activation mapping was © 2016 American Heart Association, Inc. Original Article Circ Arrhythm ElectrophysiolBackground-Noninvasive imaging of cardiac activation before ablation of the arrhythmogenic substrate can reduce electrophysiological procedure duration and help choosing between an endocardial or epicardial approach. A noninvasive imaging technique was evaluated that estimates both endocardial and epicardial activation from body surface potential maps. We performed a study in isolated and in situ pig hearts, estimating activation from body surface potential maps during sinus rhythm and localizing endocardial and epicardial stimulation sites. Methods and Results-From 3 Langendorff-perfused pig hearts, 180 intramural unipolar electrograms were recorded during sinus rhythm and ectopic activation, together with pseudo-body surface potential map ECGs in 2 of them. From 4 other anesthetized pigs, 64-lead body surface potential maps were recorded during sinus rhythm and ventricular stimulation from 27 endocardial and epicardial sites. The ventricular activation pattern was computed from the recorded QRS complexes. For both Langendorff-perfused hearts, the calculated epicardial and endocardial activation patterns showed good qualitative correspondence to the patterns obtained with needle electrodes. Absolute timing difference for sinus rhythm was 10±5 and 11±8 ms respectively, and for ectopic activation 6±5 and 7±6 ms, respectively. Calculated activation for the in situ hearts in sinus rhythm was similar to patterns recorded in Langendorff-perfused hearts. During stimulation, the distance between the stimulation site and calculated site of earliest activation was 18 (15-27) mm, and 23 of 27 stimulation sites were correctly mapped to either endocardium or epicardium. performed in Langendorff-perfused, isolated pig hearts, while recording pseudo body surface maps (BSMs) from the boundary of a fluid-filled container with integrated electrodes in which the heart was suspended. In part II, BSMs and catheter electrograms were recorded simultaneously in intact pigs. The data from part I were used to adapt our inverse method to porcine electrophysiology and to evaluate it using a simple, homogeneous volume conductor (ie, the fluid-filled container), with transmural activation mapping as a reference. However, BSMs are measured on the surface of the torso, which is irregularly shaped, and contains organs with low conductivity (eg, lungs) and blood with high conductivity. This will affect the current distribution within the thorax and, thereby, the potentials generated at the body surface. Therefore, experiments in intact adult pigs were used to show the ability of our noninvasive mapping technique to reliably determine ventricular activation and dis...

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Chronic complete atrioventricular block dogs susceptible for TdP demonstrate higher RT differences. Torsade de pointes arises from a region with maximal heterogeneity of repolarization suggesting that a minimal gradient is required in order to initiate TdP.

Background and PurposeEnhanced late sodium current (late I Na) in heart failure and long QT syndrome type 3 is proarrhythmic. This study investigated the antiarrhythmic effect and mode of action of the selective and potent late I Na inhibitor GS‐458967 (GS967) against Torsades de Pointes arrhythmias (TdP) in the chronic atrioventricular block (CAVB) dog.Experimental ApproachElectrophysiological and antiarrhythmic effects of GS967 were evaluated in isolated canine ventricular cardiomyocytes and CAVB dogs with dofetilide‐induced early afterdepolarizations (EADs) and TdP, respectively. Mapping of intramural cardiac electrical activity in vivo was conducted to study effects of GS967 on spatial dispersion of repolarization.Key ResultsGS967 (IC50~200nM) significantly shortened repolarization in canine ventricular cardiomyocytes and sinus rhythm (SR) dogs, in a concentration and dose‐dependent manner. In vitro, despite addition of 1μM GS967, dofetilide‐induced EADs remained present in 42% and 35% of cardiomyocytes from SR and CAVB dogs, respectively. Nonetheless, GS967 (787±265nM) completely abolished dofetilide‐induced TdP in CAVB dogs (10/14 after dofetilide to 0/14 dogs after GS967), while single ectopic beats (sEB) persisted in 9 animals. In vivo mapping experiments showed that GS967 significantly reduced spatial dispersion of repolarization: cubic dispersion was significantly decreased from 237±54ms after dofetilide to 123±34ms after GS967.Conclusion and ImplicationsGS967 terminated all dofetilide‐induced TdP without completely suppressing EADs and sEB in vitro and in vivo, respectively. The antiarrhythmic mode of action of GS967, through the reduction of spatial dispersion of repolarization, seems to predominantly impede the perpetuation of arrhythmic events into TdP rather than their initiating trigger.

TdP can be driven by focal activity as well as by re-entry depending on the duration of the episode. NT episodes are always maintained by re-entry, which can be identified in local unipolar electrograms by shorter interbeat intervals and smaller deflection amplitude.

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