Background—: Substrate-based mapping for ventricular tachycardia (VT) ablation is hampered by its inability to determine critical sites of the VT circuit. We hypothesized that those potentials, which delay with a decremental extrastimulus (decrement evoked potentials or DEEPs), are more likely to colocalize with the diastolic pathways of VT circuits. Methods and Results—: DEEPs were identified in intraoperative left ventricular maps from 6 patients with ischemic cardiomyopathy (total 9 VTs) and were compared with late potential (LP) and activation maps of the diastolic pathway for each VT. Mathematical modeling was also used to further validate and elucidate the mechanisms of DEEP mapping. All patients demonstrated regions of DEEPs and LPs. The mean endocardial surface area of these potentials was 18±4% and 21±6%, respectively ( P =0.13). The mean sensitivity for identifying the diastolic pathway in VT was 50±23% for DEEPs and 36±32% for LPs ( P =0.31). The mean specificity was 43±23% versus 20±8% for DEEP and LP mapping, respectively ( P =0.031). The electrograms that displayed the greatest decrement in each case had a sensitivity and specificity for the VT isthmus of 29±10% and 95±1%, respectively. Mathematical modeling studies recapitulated DEEPs at the VT isthmus and demonstrated their role in VT initiation with a critical degree of decrement. Conclusions—: In this preliminary study, DEEP mapping was more specific than LP mapping for identifying the critical targets of VT ablation. The mechanism of DEEPs relates to conduction velocity restitution magnified by zigzag conduction within scar channels.

Background—With its inherent limitations, determining local activation times has been the basis of cardiac mapping for over a century. Here, we introduce omnipolar electrograms that originate from the natural direction of a travelling wave and from which instantaneous conduction velocity amplitude and direction can be computed at any single location without first determining activation times. We sought to validate omnipole-derived conduction velocities and explore potential application for localization of sources of arrhythmias. Methods and Results—Electrograms from omnipolar mapping were derived and validated using 4 separate models and 2 independent signal acquisition methodologies. We used both electric signals and optical signals collected from monolayer cell preparations, 3-dimensional constructs built with cardiomyocytes derived from human embryonic stem cells, simultaneous optical and electric mapping of rabbit hearts, and in vivo pig electrophysiology studies. Conduction velocities calculated from omnipolar electrograms were compared with wavefront propagation from optical and electric-mapping studies with a traditional local activation time–based method. Bland–Altman analysis revealed that omnipolar measurements on optical data were in agreement with local activation time methods for wavefront direction and velocity within 25 cm/s and 30°, respectively. Similar agreement was also found on electric data. Furthermore, mathematical operations, such as curl and divergence, were applied to omnipole-derived velocity vector fields to locate rotational and focal sources, respectively. Conclusions—Electrode orientation–independent cardiac wavefront trajectory and speed at a single location for each cardiac activation can be determined accurately with omnipolar electrograms. Omnipole-derived vector fields, when combined with mathematical transforms may aid in real-time detection of cardiac activation sources.

Background: Low-voltage–guided substrate modification is an emerging strategy in atrial fibrillation (AF) ablation. A major limitation to contemporary bipolar electrogram (EGM) analysis in AF is the resultant lower peak-to-peak voltage (V _pp ) from variations in wavefront direction relative to electrode orientation and from fractionation and collision events. We aim to compare bipole V _pp with novel omnipolar peak-to-peak voltages (V _max ) in sinus rhythm (SR) and AF. Methods and Results: A high-density fixed multielectrode plaque was placed on the epicardial surface of the left atrium in dogs. Horizontal and vertical orientation bipolar EGMs, followed by omnipolar EGMs, were obtained and compared in both SR and AF. Bipole orientation has significant impact on bipolar EGM voltages obtained during SR and AF. In SR, vertical values were on average 66±119% larger than horizontal ( P =0.004). In AF, vertical values were on average 31±96% larger than horizontal ( P =0.07). Omnipole V _max values were 99.9±125% larger than both horizontal (99.9±125%; P <0.001) and vertical (41±78%; P <0.0001) in SR and larger than both horizontal (76±109%; P <0.001) and vertical (52±70%; P value <0.0001) in AF. Vector field analysis of AF wavefronts demonstrates that omnipolar EGMs can account for collision and fractionation and record EGM voltages unaffected by these events. Conclusions: Omnipolar EGMs can extract maximal voltages from AF signals which are not influenced by directional factors, collision or fractionation, compared with contemporary bipolar techniques.

Background—: Resistant ventricular fibrillation, refibrillation. and diminished myocardial contractility are important factors leading to poor survival after cardiac arrest. We hypothesized that dantrolene improves survival after ventricular fibrillation (VF) by rectifying the calcium dysregulation caused by VF. Methods and Results—: VF was induced in 26 Yorkshire pigs for 4 minutes. Cardiopulmonary resuscitation was then commenced for 3 minutes, and dantrolene or isotonic saline was infused at the onset of cardiopulmonary resuscitation. Animals were defibrillated and observed for 30 minutes. To study the effect of VF on calcium handling and its modulation by dantrolene, hearts from 14 New Zealand rabbits were Langendorff-perfused. The inducibility of VF after dantrolene administration was documented. Optical mapping was performed to evaluate diastolic spontaneous calcium elevations as a measure of cytosolic calcium leak. The sustained return of spontaneous circulation (systolic blood pressure ≥60 mm Hg) was achieved in 85% of the dantrolene group in comparison with 39% of controls ( P =0.02). return of spontaneous circulation was achieved earlier in dantrolene-treated pigs after successful defibrillation (21±6 s versus 181±57 s in controls, P =0.005). The median number of refibrillation episodes was lower in the dantrolene group (0 versus 1, P =0.04). In isolated rabbit hearts, the successful induction of VF was achieved in 83% of attempts in controls versus 41% in dantrolene-treated hearts ( P =0.007). VF caused diastolic calcium leaks in the form of spontaneous calcium elevations. Administration of 20 μmol/L dantrolene significantly decreased spontaneous calcium elevation amplitude versus controls. (0.024±0.013 versus 0.12±0.02 arbitrary unit [200-ms cycle length], P =0.001). Conclusions—: Dantrolene infusion during cardiopulmonary resuscitation facilitates successful defibrillation, improves hemodynamics postdefibrillation, decreases refibrillation, and thus improves survival after cardiac arrest. The effects are mediated through normalizing VF-induced dysfunctional calcium cycling.