Cardioversion of persistent atrial fibrillation is associated with a 24-hour relapse gap: Observations from prolonged postcardioversion rhythm monitoring.

BACKGROUND: Many recurrences occur after electrical cardioversion (ECV) of atrial fibrillation (AF). Assessment of extent of remodeling and continuous prolonged rhythm monitoring might reveal actionable recurrence mechanisms. HYPOTHESIS: After ECV of AF specific patterns of arrhythmia recurrence can be distinguished. METHODS: All patients who underwent successful ECV due to persistent AF were included. Tissue velocity echocardiography during AF was performed before ECV to study atrial fibrillatory cycle length and fibrillatory velocity. After ECV, the heart rhythm of all patients was monitored 3 times daily during 4 weeks, and timing of recurrence was noted. RESULTS: In total, 50 patients (68% male) were included; mean age was 68 ± 9 years. Median duration of the current AF episode was 102 (range, 74-152) days. Twenty-one (42%) patients showed recurrence of persistent AF. No recurrences occurred during the first 24 hours. There were no differences in clinical characteristics between patients with or without recurrence of AF. However, patients with early recurrence of AF had significantly higher precardioversion wall-motion velocity compared with patients who remained in sinus rhythm (2.8 [1.6-3.6] vs 1.4 [0.9-3.3] cm/s; P = 0.017), whereas atrial fibrillatory cycle length did not differ. CONCLUSIONS: In this study on 50 patients successfully cardioverted for persistent AF, there was a relapse gap of ≥24 hours. This phenomenon has not been well appreciated before and offers an AF-free window of opportunity for electrocardiographically triggered cardiac imaging or complex electrophysiological procedures. Echocardiographic tissue velocity imaging may visualize atrial remodeling relevant to AF recurrence.

Electropathological substrate of longstanding persistent atrial fibrillation in patients with structural heart disease: epicardial breakthrough.

BACKGROUND: During persistent atrial fibrillation (AF), waves with a focal spread of activation are frequently observed. The origin of these waves and their relevance for the persistence of AF are unknown. METHODS AND RESULTS: In 24 patients with longstanding persistent AF and structural heart disease, high-density mapping of the right and left atria was performed during cardiac surgery. In a reference group of 25 patients, AF was induced by rapid pacing. For data analysis, a mapping algorithm was developed that separated the fibrillatory process into its individual wavelets and identified waves with a focal origin. During persistent AF, the incidence of focal fibrillation waves in the right atrium was almost 4-fold higher than during acute AF (median, 0.46 versus 0.12 per cycle per 1 cm² (25th to 75th percentile, 0.40 to 0.77 and 0.01 to 0.27; P<0.0001). They were widely distributed over both atria and were recorded at 46 ± 18 of all electrodes. A large majority (90.5) occurred as single events. Repetitive focal activity (>3) happened in only 0.8. The coupling interval was not more than 11 ms shorter than the average AF cycle length (P=0.04), and they were not preceded by a long interval. Unipolar electrograms at the site of origin showed small but clear R waves. These data favor epicardial breakthrough rather than a cellular focal mechanism as the underlying mechanism. Often, conduction from a site of epicardial breakthrough was blocked in 1 or more directions. This generated separate multiple wave fronts propagating in different directions over the epicardium. CONCLUSIONS: Focal fibrillation waves are due to epicardial breakthrough of waves propagating in deeper layers of the atrial wall. In patients with longstanding AF, the frequency of epicardial breakthroughs was 4 times higher than during acute AF. Because they provide a constant source of independent fibrillation waves originating over the entire epicardial surface, they offer an adequate explanation for the high persistence of AF in patients with structural heart disease.

Electropathological substrate of long-standing persistent atrial fibrillation in patients with structural heart disease: longitudinal dissociation.

BACKGROUND: The electropathological substrate of persistent atrial fibrillation (AF) in humans is largely unknown. The aim of this study was to compare the spatiotemporal characteristics of the fibrillatory process in patients with normal sinus rhythm and long-standing persistent AF. METHODS AND RESULTS: During cardiac surgery, epicardial mapping (244 electrodes) of the right atrium (RA), the left lateral wall (LA), and the posterior left atrium (PV) was performed in 24 patients with long-standing persistent AF. Twenty-five patients with normal sinus rhythm, in whom AF was induced by rapid pacing, served as a reference group. A mapping algorithm was developed that separated the complex fibrillation process into its individual elements (wave mapping). Parameters used to characterize the substrate of AF were (1) the total length of interwave conduction block, (2) the number of fibrillation waves, and (3) the ratio of block to collision of fibrillation waves (dissociation index). In 4403 maps of persistent AF, no evidence for the presence of stable foci or rotors was found. Instead, many narrow wavelets propagated simultaneously through the atrial wall. The lateral boundaries of these waves were formed by lines of interwave conduction block, predominantly oriented parallel to the atrial musculature. Lines of block were not fixed but continuously changed on a beat-to-beat basis. In patients with persistent AF, the total length of block in the RA was more than 6-fold higher than during acute AF (median, 21.1 versus 3.4 mm/cm(2); P<0.0001). The highest degree of interwave conduction block was found in the PV area (33.0 mm/cm(2)). The number of fibrillation waves during persistent AF was 4.5/cm(2) compared with 2.3 during acute AF, and the dissociation index was 7.3 versus 1.5 (P<0.0001). The interindividual variation of these parameters among patients was high. CONCLUSIONS: Electric dissociation of neighboring atrial muscle bundles is a key element in the development of the substrate of human AF. The degree of the pathological changes can be measured on an individual basis by electrophysiological parameters in the spatial domain.

Analysis of fractionated atrial fibrillation electrograms by wavelet decomposition.

This study introduces the use of wavelet decomposition of unipolar fibrillation electrograms for the automatic detection of local activation times during complex atrial fibrillation (AF). The purpose of this study was to evaluate this technique in patients with structural heart disease and longstanding persistent AF. In 46 patients undergoing cardiac surgery, unipolar fibrillation electrograms were recorded from the right atrium, using a mapping array of 244 electrodes. In 25 patients with normal sinus rhythm, AF was induced by rapid pacing, whereas 21 patients were in persistent AF. In patients with longstanding AF, the atrial electrograms showed a high degree of fractionation. In each patient, 12 s of AF were analyzed by wavelet transformation (15 scales). The finest scales (1-7) were used to reconstruct a "local" fibrillation electrogram, whereas with the coarse scales (9-15), a far-field signal was generated. With these local and far-field electrograms, the "primary" fibrillation potentials, due to wave propagation underneath the electrode, could be distinguished from double potentials and multiple components generated by remote wavefronts. Wavelet transformation resulted in AF histograms with a closely gaussian distribution and the automatically generated activation maps showed a good resemblance with fibrillation maps obtained by laborious manual editing. A special chaining algorithm was developed to detect multiple components in fractionated electrograms. The degree of fractionation showed a positive correlation with the complexity of fibrillation, thus providing an objective quantification of the degree of electrical dissociation of the atria. Wavelet transformation can be a useful technique to detect the primary potentials and quantify the degree of fractionation of fibrillation electrograms. This could enable real-time mapping of complex cases of human AF and classification of the underlying electropathological substrate.

Improving sensing and detection performance in subcutaneous monitors.

Implantable loop recorders (ILRs) are used for continuous assessment of patients at risk for syncope and arrhythmia. Device accuracy depends on appropriate sensing of the patient's electrocardiogram (ECG) signal. However, current methods for sensing cardiac electrical activity rely on simple threshold detectors that are computationally efficient but nonspecific. We test the hypothesis that better ILR implant positions will increase detection accuracy. Ten healthy subjects were studied as they assumed 12 different postures. Body surface potential map (BSM) recordings were used to estimate bipolar R-wave amplitudes for 64 potential implant sites at 360 orientations per site. Optimal sites were identified as the combination of position and orientation that consistently gave the largest signal and the lowest variability during posture changes. Results showed that posture impacts the R-wave amplitude in both BSM and derived bipolar ECGs in healthy subjects. Specific postures are associated with significant drops in R-wave signal amplitude that could cause loss of signal detection in ILRs, especially in positions likely to displace the diaphragm. R-wave changes occurred abruptly as posture was changed. Optimal implant locations cluster near the center of the chest, aligned with the cardiac axis, consistent with the steeper isoelectric gradients known to be associated with these positions.

Automatic mapping of human atrial fibrillation by template matching.

BACKGROUND: The high spatiotemporal variation in morphology of fibrillation electrograms makes mapping of atrial fibrillation (AF) a difficult and burdensome task. OBJECTIVES: The purpose of this study was to evaluate the results of automatic detection of fibrillation electrograms by a template matching technique. METHODS: During cardiac surgery in 25 patients without a history of AF, paroxysms of AF were induced by rapid atrial pacing. A mapping array of 244 unipolar electrodes (3.6-cm diameter, 2.25-mm interelectrode distance) was positioned on the free wall of the right atrium. All fibrillation electrograms were correlated with a mathematically constructed library of 128 potentials of different duration, RS ratio, and short double components. The moments of maximal correlation, coinciding with the negative deflection in the fibrillation potentials, were used to create fibrillation maps. RESULTS: In each patient, a segment of 18.6 +/- 3.8 seconds of AF was analyzed, resulting in 80 to 130 maps per patient. The output of the automatic algorithm was compared with careful manual analysis by an experienced investigator. Of the total database of 398,796 fibrillation potentials, 93.6% +/- 4.2% resulted in a good correlation with one of the templates in the library (correlation coefficient >= 0.7). At a correlation threshold of 0.6, on average template matching yielded slightly more false-positive than false-negative detections (sensitivity 96.6% +/- 2.5%, positive predictive value 94.3% +/- 5.4%). The majority of false-positive detections were due to electrotonic potentials recorded along the lateral boundaries of the fibrillation waves. This led to a slight overlap of fibrillation waves but not to false detection of nonexisting wavefronts. Undersensing was mainly due to the presence of long double and fractionated potentials (2.6%) that were not represented in the template library. Fractionated parts in the electrograms were identified by failure of template matching and can be analyzed separately. CONCLUSION: Template matching is a useful technique for characterizing unipolar fibrillation electrograms and for visualizing the complex activation patterns during AF. It allows automatic evaluation of the electropathologic substrate of AF on an individual basis.

Synergistic action of atrial dilation and sodium channel blockade on conduction in rabbit atria.

INTRODUCTION: The aim of this study was to investigate the interaction of atrial dilation and blockade of the rapid sodium channel on atrial conduction and degree of anisotropy. METHODS AND RESULTS: The right atrium was acutely dilated by increasing intra-atrial pressure from 2 to 9 cm H2O in 14 isolated rabbit hearts. A rectangular mapping array of 240 electrodes (spatial resolution 0.5 mm) was positioned on the free wall of the right atrium during pacing from four different directions at intervals of 240 and 140 msec. In nondilated atria, 0.5 and 1.0 mg/L of the use-dependent INa blocker flecainide prolonged the total conduction time under the mapping electrode by 15% to 75%. In dilated atria, flecainide depressed conduction by 24% to 89% (P < 0.05). The incidence of intra-atrial conduction block increased from 0.6%-0.8% to 3.3%-7.2% in nondilated atria and from 3.9%-4.6% to 13%-21% in dilated atria (P < 0.05). The direction of activation relative to the crista terminalis and major pectinate muscles was of major importance for occurrence of conduction block. During rapid pacing, the degree of anisotropy in conduction increased by the combination of atrial dilation and flecainide (1.0 mg/L) from 1.7 +/- 0.1 to 2.2 +/- 0.4 (P < 0.05). The effects of dilation and flecainide on conduction were clearly synergistic. The effect of flecainide on the atrial refractory period also was enhanced by atrial dilation. CONCLUSION: In dilated atria, blockade of the rapid sodium channels caused a higher degree of local conduction delay and intra-atrial conduction block than in nondilated atria.

S-wave predominance of epicardial electrograms during atrial fibrillation in humans: indirect evidence for a role of the thin subepicardial layer.

OBJECTIVES: The purpose of this study was to characterize the morphology of fibrillation electrograms in patients in order to provide insight into the underlying electropathologic substrate of atrial fibrillation (AF). BACKGROUND: Electrograms recorded during AF show a high degree of spatiotemporal variation. METHODS: AF was induced by rapid atrial pacing in 25 patients undergoing cardiac surgery. A unipolar mapping array of 244 electrodes was positioned on the free wall of the right atrium to record multiple epicardial fibrillation electrograms. Local anisotropy in conduction and epicardial wavefront curvature during AF were determined by fitting the best quadratic surface on the activation times of rectangular areas of 3 x 3 electrodes. RESULTS: During AF, unipolar epicardial electrograms revealed a clear predominance of S waves. The average RS difference during type I and II AF was -0.15 +/- 0.08 and -0.22 +/- 0.08. During type III AF, the predominance of S waves was less prominent (-0.07 +/- 0.05; P < .005). In all types of AF, the degree of anisotropy in conduction was remarkably low (anisotropy ratio: 1.24 +/- 0.09), and no clear directional effect on the relative amplitude of R and S waves was found. There was a weak relationship between local curvature of wavefronts and RS difference (r = 0.23; P < .01). Computer simulations showed that the negative RS difference could result from transmural activation in an epicardial to endocardial direction. CONCLUSIONS: The clear predominance of S waves in epicardial fibrillation electrograms is not due to anisotropy and can only be partly explained by a high curvature of fibrillation waves. Predominant epicardial to endocardial activation seems to be important in producing rS electrograms on the epicardium. This finding provides indirect evidence that the thin epicardial layer of atrial myocardium plays an important role in propagation of fibrillation waves.