Fibrillation Activation Research Articles

Usefulness of 3D Mapping in Catheter Ablation of Residual AF Driver Showing Fibrillatory Activation in Isolated SVC

Usefulness of 3D Mapping in Catheter Ablation of Residual AF Driver Showing Fibrillatory Activation in Isolated SVC

Ranolazine-Mediated Attenuation of Mechanoelectric Feedback in Atrial Myocyte Monolayers.

BackgroundMechanical stretch increases Na+ inflow into myocytes, related to mechanisms including stretch-activated channels or Na+/H+ exchanger activation, involving Ca2+ increase that leads to changes in electrophysiological properties favoring arrhythmia induction. Ranolazine is an antianginal drug with confirmed beneficial effects against cardiac arrhythmias associated with the augmentation of INaL current and Ca2+ overload.ObjectiveThis study investigates the effects of mechanical stretch on activation patterns in atrial cell monolayers and its pharmacological response to ranolazine.MethodsConfluent HL-1 cells were cultured in silicone membrane plates and were stretched to 110% of original length. The characteristics of in vitro fibrillation (dominant frequency, regularity index, density of phase singularities, rotor meandering, and rotor curvature) were analyzed using optical mapping in order to study the mechanoelectric response to stretch under control conditions and ranolazine action.ResultsHL-1 cell stretch increased fibrillatory dominant frequency (3.65 ± 0.69 vs. 4.35 ± 0.74 Hz, p < 0.01) and activation complexity (1.97 ± 0.45 vs. 2.66 ± 0.58 PS/cm2, p < 0.01) under control conditions. These effects were related to stretch-induced changes affecting the reentrant patterns, comprising a decrease in rotor meandering (0.72 ± 0.12 vs. 0.62 ± 0.12 cm/s, p < 0.001) and an increase in wavefront curvature (4.90 ± 0.42 vs. 5.68 ± 0.40 rad/cm, p < 0.001). Ranolazine reduced stretch-induced effects, attenuating the activation rate increment (12.8% vs. 19.7%, p < 0.01) and maintaining activation complexity—both parameters being lower during stretch than under control conditions. Moreover, under baseline conditions, ranolazine slowed and regularized the activation patterns (3.04 ± 0.61 vs. 3.65 ± 0.69 Hz, p < 0.01).ConclusionRanolazine attenuates the modifications of activation patterns induced by mechanical stretch in atrial myocyte monolayers.

Interpreting Activation Mapping of Atrial Fibrillation: A Hybrid Computational/Physiological Study.

Atrial fibrillation is the most common rhythm disorder of the heart associated with a rapid and irregular beating of the upper chambers. Activation mapping remains the gold standard to diagnose and interpret atrial fibrillation. However, fibrillatory activation maps are highly sensitive to far-field effects, and often disagree with other optical mapping modalities. Here we show that computational modeling can identify spurious non-local components of atrial fibrillation electrograms and improve activation mapping. We motivate our approach with a cohort of patients with potential drivers of persistent atrial fibrillation. In a computational study using a monodomain Maleckar model, we demonstrate that in organized rhythms, electrograms successfully track local activation, whereas in atrial fibrillation, electrograms are sensitive to spiral wave distance and number, spiral tip trajectories, and effects of fibrosis. In a clinical study, we analyzed n=15 patients with persistent atrial fibrillation that was terminated by limited ablation. In five cases, traditional activation maps revealed a spiral wave at sites of termination; in ten cases, electrogram timings were ambiguous and activation maps showed incomplete reentry. By adjusting electrogram timing through computational modeling, we found rotational activation, which was undetectable with conventional methods. Our results demonstrate that computational modeling can identify non-local deflections to improve activation mapping and explain how and where ablation can terminate persistent atrial fibrillation. Our hybrid computational/physiological approach has the potential to optimize map-guided ablation and improve ablation therapy in atrial fibrillation.

Noninvasive Mapping of Human Atrial Fibrillation

Invasive high-density mapping of atrial fibrillation (AF) has revealed different patterns of atrial activation ranging from single wavefronts to disorganized activation with multiple simultaneous wavefronts. Whether or not similar activation patterns can also be observed using body surface recordings is currently unknown, and was consequently evaluated in this study. Surface electrocardiographic mapping was performed in 14 patients (age 68 +/- 14 years) with persistent AF (AF duration 12 +/- 18 months). A total of 56 electrocardiographic leads were placed on the chest over the atria on the front (n = 40) and on the back (n = 16). Using 240-second recordings, wavefront propagation maps were automatically computed and visually classified as either type I (single wavefront), II (single wavefront with wave breakages and splitting), or III (multiple simultaneous wavefronts). Almost half of the patients (n = 6) presented most predominantly type III atrial activation, while six patients mostly presented type I activation. The rest of the patients (n = 2) presented mixed type I and type III activations. This classification showed to be highly reproducible over 4 minutes. Using electrocardiographic body surface mapping during AF, interindividual differences of atrial fibrillatory activation can be observed. The surface activation pattern during AF shows an excellent short-term reproducibility.

Electrophysiological Abnormalities Occur Prior to the Development of Clinical Episodes of Atrial Fibrillation: Observations from Human Epicardial Mapping

Atrial fibrillation (AF) is characterized by irregular atrial activation maintained by an arrhythmogenic substrate. We addressed the hypothesis that the substrate of human AF includes changes in atrial conduction properties. Patients in sinus rhythm (SR) and permanent AF undergoing cardiac surgery underwent right atrial epicardial mapping. AF was induced by burst pacing in patients in SR and was defined as sustained at >30 seconds. Epicardial maps were analyzed to determine conduction properties, AF activation patterns, and refractoriness. Patients in SR underwent postoperative Holter monitoring. Thirty-seven subjects were recruited. (27 in SR and 10 in permanent AF). Sustained AF was induced in 17 patients in SR. Only patients with sustained AF developed any episodes of postoperative AF (P < 0.05), indicating the preexistence of an arrhythmogenic substrate, which was characterized by prolonged unipolar electrograms (37.0 +/- 9.4 ms vs 27.5 +/- 6.4 ms, P = 0.03), particularly in the region of the crista terminalis (41.2 ms +/- 12.1 vs 26.7 ms +/- 5.8, P = 0.004) compared with the nonsustaining group. However, these differences in electrogram characteristics were not associated with changes in wavefront propagation velocity (WPV) during SR or pacing. Activation mapping of acutely induced AF was compared with permanent AF and although there were shorter mean fibrillation intervals in permanent AF (171 +/- 16 ms vs 229 +/- 51 ms, P < 0.001), there was no difference in fibrillatory activation pattern (complexity scores: 2.21 +/- 0.52 vs 2.02 +/- 0.61) or WPV (46.9 +/- 15.4 cm/s vs 53.5 +/- 17.6 cm/s, P = 0.37). Fibrillatory activation pattern was associated with both WPV (P = 0.03) and wavelength (P = 0.03) in both pacing-induced and permanent AF. Patients in SR capable of sustaining pacing-induced AF have differences in electrogram duration, which are apparent before clinical episodes of AF. Although patients with permanent AF had shortening of refractoriness, there was no evidence of further changes in fibrillatory activation pattern or macroscopic wavefront propagation velocity in permanent AF. These results imply that changes occur before the onset of AF and indicate the presence of a substrate capable of maintaining AF with only alterations in refractoriness required for the development of permanent AF.

Spontaneous Localized Persistent Atrial Fibrillation with an Exit Block Mimicking Atrial Tachycardia at the Left Posterior Wall

We describe a 37‐year‐old man with spontaneous localized atrial fibrillation (AF) with an exit block at the posterior wall of the left atrium (LA). The 12‐lead ECG exhibited an atrial tachycardia‐like pattern, with distinctive P waves and an isoelectric baseline between the P waves. The cycle length of the P waves ranged from 320 to 500 msec. While the fractionated and rapid deflections were recorded from the posterior wall of the LA, the rest of the atria and the coronary sinus exhibited discrete atrial potentials with irregular intervals. Radiofrequency energy applications to the surrounding tissue created complete isolation of the localized AF area, and the AF was terminated. Fibrillatory activation in the posterior wall of the LA can act as a driver as well as an initiator of atrial fibrillation.

Spontaneous Localized Persistent Atrial Fibrillation with an Exit Block Mimicking Atrial Tachycardia at the Left Posterior Wall

We describe a 37-year-old man with spontaneous localized atrial fibrillation (AF) with an exit block at the posterior wall of the left atrium (LA). The 12-lead ECG exhibited an atrial tachycardia-like pattern, with distinctive P waves and an isoelectric baseline between the P waves. The cycle length of the P waves ranged from 320 to 500 msec. While the fractionated and rapid deflections were recorded from the posterior wall of the LA, the rest of the atria and the coronary sinus exhibited discrete atrial potentials with irregular intervals. Radiofrequency energy applications to the surrounding tissue created complete isolation of the localized AF area, and the AF was terminated. Fibrillatory activation in the posterior wall of the LA can act as a driver as well as an initiator of atrial fibrillation.

Refractory period extension during ventricular pacing at fibrillatory pacing rates.

Refractory period extension (RPE) has been proposed as a basic mechanism for defibrillation but it remains unclear if RPE exists at the fast rates associated with ventricular fibrillation. In 7 pentobarbital anesthetized dogs, we measured refractory periods with and without 8 ms rectangular transcardiac shocks at left ventricular pacing rates of 200-600 beats/min. To achieve these high rates, an incremental rate pacing method was used to produce pacing train timing sequences requiring 4.5-27 seconds. A variably timed premature stimulus followed the last stimulus in each pacing train. To determine refractoriness, a 128 electrode array (4 x 4 cm) was used to detect the presence, or absence of an activation sequence sweeping away from the pacing site. At each rate, a control refractory period (RPc) was measured and refractory periods were also measured for 8 and 12 V/cm shocks with coupling intervals of 60% to 90% of RPc. RPc decreased as the rate increased with a minimum RPc of 94 ms at a rate of 600 beats/min (100 ms cycle length). RPE/RPc versus shock coupling interval was similar at all pacing rates. RPE/RPc increased with increased coupling interval or higher shock intensity. We conclude that during ventricular pacing at fibrillatory rates tissue is nearly always in a refractory state; that RPE exists at fibrillatory activation rates; and that RPE/RPc versus shock coupling interval does not vary strongly with pacing rate. These findings support the hypothesis that RPE contributes to defibrillation.