(Circulation. 1997;95:1231-1241.)
© 1997 American Heart Association, Inc.
Articles |
Configuration of Unipolar Atrial Electrograms During Electrically Induced Atrial Fibrillation in Humans
the Department of Physiology, Cardiology and Cardiopulmonary Surgery, Cardiovascular Research Institute Maastricht, Maastricht University, the Netherlands.
Correspondence to Prof Dr M.A. Allessie, Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, PO Box 616, 6200 MD Maastricht, Netherlands.
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Abstract |
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Background During atrial fibrillation (AF), the atrium is activated by multiple wavelets that continuously change in size and direction. The aim of this study was to correlate the temporal variation in AF electrogram configuration with the varying spatial patterns of activation.
Methods and Results In a group of 25 Wolff-Parkinson-White patients undergoing cardiac surgery, the free wall of the right atrium was mapped (244 points) during electrically induced AF. The unipolar electrograms recorded during 4 seconds of AF were classified into four categories: (1) single deflections, (2) short-double potentials, (3) long-double potentials, and (4) fragmented potentials. The proportion of these four types of electrograms during AF was as follows: singles, 77±12%; short-doubles, 7±3%; long-doubles, 10±7%; and fragmented, 6±4%. Electrogram morphology was an indicator for rapid uniform conduction (single potentials; positive predictive value [PPV] of 0.96), collision (short-double potentials; PPV of 0.33), conduction block (long-double potentials; PPV of 0.84), and pivoting points or slow conduction (fragmented potentials; PPV of 0.87). In type I, II, and III AF, the proportion of long-double potentials was 4±2%, 12±3%, and 18±7% (P<.05); the proportion of fragmented complexes was 2±2%, 6±3%, and 10±4% (P<.05), respectively. During electrically induced and self-terminating episodes of AF, no preferential anatomic sites for double or fragmented potentials were found in the right atrium.
Conclusions The morphology of single unipolar electrograms during AF reflects the occurrence of various specific patterns of conduction. This might be used to differentiate between different types of AF and to identify regions with structural conduction disturbances involved in perpetuation of chronic AF.
Key Words: atrium • arrhythmia • fibrillation • mapping • reentry
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On the basis of recording single bipolar atrial electrograms, Wells et al1 in 1978 distinguished four different types of AF occurring within the first week of cardiac surgery. Type I was characterized by discrete complexes separated by an isoelectric baseline free of perturbations. Type II also showed discrete atrial complexes, but the baseline between the major deflections was, to varying degrees, disturbed by smaller deflections. In type III, no discrete complexes could be distinguished, and the bipolar electrograms were described as being "totally chaotic in nature." Type IV actually was a mixture of the other types in which episodes of type III were alternating with electrogram morphologies as seen during type I or II fibrillation.
Using a high-density mapping electrode with a diameter of 3.6 cm containing 244 unipolar electrodes, we have mapped the activation of the free wall of the right and left atria during electrically induced AF in 25 WPW patients undergoing cardiac surgery.2 On the basis of the degree of complexity of the activation maps, three types of AF were distinguished. In type I, the atria were activated by broad activation waves propagating uniformly with a still relatively high conduction velocity of 
60 cm/s. During type II fibrillation, arcs of functional intra-atrial conduction block were present, and the mapping area was activated by two different fibrillation waves. In type III, the atria were activated in a highly complex manner by multiple slowly conducting wavelets (38 cm/s) separated by multiple lines of functional conduction block, which continuously shifted in size and location. In this most complex type of AF, long episodes of continuous electrical activity were recorded in the free wall of the right and left atrium. Like in the study of Wells et al,1 temporal variations in the type of activation were commonly observed, but instead of classifying this as a separate type of AF, we considered this a general feature of AF.2
Numerous studies have investigated the effects of factors like slow conduction,3 4 5 6 7 8 9 tissue anisotropy,9 10 11 12 conduction block,3 6 10 12 13 14 reentry,3 9 10 12 and collision of activation waves15 on the morphology of unipolar and bipolar electrograms. However, it is still unknown to what extent these various factors contribute to the temporal and spatial variations in electrogram morphology as observed during AF. Obviously, this seriously limits the interpretation of fibrillation electrograms. Because high-density mapping can be used only in a limited and selected number of cases, it would be useful if single fibrillation electrograms recorded during catheterization could be "translated" into certain types of conduction disturbances. This not only would help to distinguish different types of atrial fibrillation but also might enable us to detect structural or functional abnormalities in the atrial walls responsible for perpetuation of AF.
The aim of the present study was to analyze the various morphologies of unipolar AF electrograms and to determine their relationship with the underlying spatial patterns of activation.
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Patient Population
The study group consisted of the same 25 patients with a WPW syndrome as described previously.2 Sixteen patients were male, and 9 were female. Ages ranged from 12 to 57 years (mean, 32±11 years). All patients underwent a preoperative electrophysiological study during which the accessory pathways were located. None of the patients had any cardiac abnormalities other than those related to the WPW syndrome (as certified by ECG, chest roentgenogram, echocardiography, and coronary angiography). In 7 patients, AF was documented previously by ECG or Holter recordings. Antiarrhythmic medication was discontinued at least 4 days before surgery. None of the patients was taking amiodarone. All patients were operated on before 1992 when radiofrequency ablation became the primary treatment of the WPW syndrome. Informed consent was obtained before surgery.
Experimental Protocol
After anesthesia with fentanyl (50 to 100 µg/kg), alfentanil (2 µg·kg-1·min-1), and propofol (2 mg·kg-1·h-1), a median sternotomy was made and the heart was exposed. A handheld spoon-shaped mapping electrode (diameter, 3.6 cm; 244 unipolar electrodes; interelectrode distance, 2.25 mm) was used to accurately localize the accessory pathway(s) intraoperatively and to map the epicardial activation of the free wall of the right atria. Before the patients were put on cardiopulmonary bypass, one or more episodes of AF were induced by rapid atrial pacing. In all patients, the epicardial excitation pattern of the free wall of the right atrium was mapped during sinus rhythm, rapid atrial pacing (interval, 180 ms), and a period of electrically induced AF.2 A silver plate (diameter, 2.5 cm) in the thoracic cavity was used as an indifferent electrode. Simultaneously with the 244 unipolar epicardial electrograms, a surface ECG (leads I, II, III, and aVR) and four bipolar reference electrograms were recorded from the right and left atria and the ventricles. After amplification (gain, 500 to 1000), the 244 unipolar atrial electrograms were filtered (bandwidth, 1 to 500 Hz), multiplexed (sampling rate, 1 kHz), converted from analog to digital (8 bits), and stored on videotape for subsequent analysis.16
Data Analysis
In each patient, one episode of AF was analyzed. From a period of stable AF, a time frame of 4 seconds was selected, and the 244 unipolar electrograms were transferred to a personal computer. The various morphologies of the unipolar atrial electrograms recorded during AF were classified into 4 categories: (1) single potentials, (2) short-double potentials, (3) long-double potentials, and (4) fragmented potentials. Fig 1
gives an example of these types of electrograms. Single potentials are characterized by a single rapid negative deflection preceded by an R wave and smoothly returning to the baseline. Double potentials were defined as two negative deflections, the amplitude of the smallest being 
25% of the amplitude of the largest. With these criteria, only double wave fronts within a distance of slightly more than about one space constant are included. Short-double potentials were defined as double potentials with a time interval between the two deflections of <10 ms. Long-double potentials were defined as electrograms showing two components separated by 10 to 50 ms. The upper limit of 50 ms was based on the assumption that the atrial refractory period during AF and the interval between two successive fibrillation waves were 50 ms. Fragmented potentials were defined as electrograms exhibiting more than two negative deflections within 50 ms. All 244 electrograms recorded during 4 seconds of AF in 25 patients were displayed individually for inspection, and each complex was classified according to the criteria given above. Electrograms that were difficult to judge because of either superimposed high-amplitude ventricular activity or poor tissue contact were discarded. The total database of all unipolar electrograms recorded during AF comprised a total of >115 000 individual complexes.
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To compare the electrogram morphology with the spatial characteristics of activation, high-density activation maps were reconstructed from the local activation times of all 244 recording sites. The software used for construction of the activation maps included an automatic detection algorithm for the most negative intrinsic deflection, generation of color-coded activation maps, and interactive editing of local activation times.16 Isochrones were drawn by hand at 10-ms intervals. Interatrial conduction block was defined as a time difference of >30 ms between two neighboring electrodes (apparent local conduction velocity <7.5 cm/s) associated with a change in direction of propagation distal to the line of block (isochrones perpendicular to the line of block).10 Slow conduction was defined as a conduction time of >30 ms associated with continuation of conduction in the same direction (isochrones parallel to the zone of slow conduction).9 17 A pivoting point was defined as the end of a line of functional block where the impulse makes a U turn. If fibrillation waves propagated toward each other, the line of collision was defined by the electrodes that were activated later than each of their neighbors.
Statistical Analysis
Results are expressed as mean±SD. Because the number of complexes varied in different patients, the proportion of the different categories of unipolar electrograms and their association with the local activation patterns are expressed as the percentage of the total number of complexes in each patient. Differences between groups were determined by Bonferroni's modification for small groups of the t test. A value of P<.05 was considered statistically significant. The relationship between electrogram configuration and spatial activation characteristics was expressed by the sensitivity, specificity, NPV, and PPV.
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Proportion of Different Types of Unipolar Atrial Electrograms
Figs 2
and 3 give the proportion of the different types of electrograms during various atrial rhythms. During sinus rhythm and rapid pacing, the majority of electrograms showed single high-amplitude rapid negative deflections (93±3% and 92±3%, respectively). During induced AF, this high proportion of single potentials decreased to 77±12% (P<.05) (Fig 2, top right). In the different subgroups of AF (Fig 2, bottom), the percentage of single potentials decreased from 88±7% in type I AF to 76±6% in type II and to 64±7% in type III (P<.05). The proportion of short-double potentials during AF was the same as during sinus rhythm or rapid pacing and averaged 7±3% (Fig 3, top right). Whereas during type I AF (10 patients) both long-double and fragmented complexes were relatively rare (4±2% and 2±2%, respectively), in type II AF (8 patients) these potentials occurred in 12±3% and 6±3%, respectively. During type III AF (7 patients), long-double potentials made up 18±7% of all complexes, whereas 10±4% of the electrograms were fragmented (Fig 3, bottom). During sinus rhythm or rapid atrial pacing, no differences in electrogram morphology were found between patients with type I, II, or III AF or between the groups of patients with (n=7) or without (n=18) spontaneous episodes of AF (Table 1).
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As Fig 4 shows, the percentage of long-double and fragmented potentials was related to the AF rate. In this figure, the relative proportion of long-double and fragmented complexes in each of the 25 patients is plotted against their median AF interval. Although there was a large interindividual variation, the percentage of long-double and fragmented potentials was higher on average at shorter fibrillation cycle lengths. The correlation coefficients of the calculated linear regression lines were .47 and .38, respectively, with P=.019 and P=.05, indicating a weak but significant correlation.
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Configuration of Unipolar Electrograms and Local Patterns of Activation
To get more insight into the mechanisms behind the different morphologies of unipolar electrograms during AF, we correlated the shape of the electrograms with the local activation maps. In Fig 5, this relationship is illustrated for some specific patterns of activation like collision (Fig 5A), conduction block (Fig 5B), pivot points (Fig 5C), and slow conduction (Fig 5D). All maps were recorded from the same area during a single episode of AF. Examples of the electrograms recorded during these events are given around the maps. In Fig 5A, four wavelets entering the mapping area from different directions (arrows) collided along the dashed line. The open squares indicate electrodes from which short-double potentials were recorded. As can be seen, almost all short-double potentials were located along either side of the line of collision. Fig 5B gives an example of functional conduction block. The wave entering the upper part of the mapping electrode at t=0 was blocked at t=20 ms as indicated by the thick line. The other wave entering the mapping area from the lower right at t=10 ms propagated rapidly from right to left along the line of block created by the first wave. The solid squares indicate electrodes from which long-double potentials were recorded. Most long-double complexes were recorded along the line of conduction block. Fig 5C shows an activation map in which three wavelets turn around the ends of arcs of functional conduction block (curved arrows). The asterisks at these pivot points indicate electrodes from which fragmented potentials were recorded. Finally, Fig 5D shows an example of slow conduction. In this example a single wave entered from the left (t=0) and propagated to the right in 130 ms. This long conduction time was caused by a zone of slow conduction in the middle of the mapping area where a crowding of seven isochrones with a total conduction delay of 60 ms can be seen. The asterisks in this band of crowded isochrones indicate the electrode sites from which long fragmented complexes were recorded.
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). B, Long-double electrograms (
) are shown to be recorded at a line of functional conduction block (thick line). Fragmented electrograms (*) were recorded both at pivot points (C) and from areas with slow conduction (D; crowding of isochrones). Isochrones were drawn at 10-ms interval. Arrows indicate the direction of activation. Numbers indicate activation times in milliseconds.
Fig 6 shows the phenomena in Fig 5
in greater detail. All unipolar electrograms (interelectrode distance, 2.25 mm) recorded in an area of 1 cm2 are displayed as signal maps, with the specific electrogram configurations highlighted. To illustrate the functional nature of the various specific electrogram configurations and to show the temporal variation in configuration caused by to beat-to-beat changes in the underlying spatial pattern of propagation, at each panel a 1-second tracing of one of the electrograms is shown. The site of recording of the specific electrogram configuration is indicated by a dot. In Fig 6A, the electrograms with short-double potentials can be accurately compared with the position of the line of collision (dashed line). The short-double potentials were recorded about one electrode distance (2.25 mm) from either side of the line of collision. Apparently, one component is caused by actual passage of one of the colliding wave fronts under the electrode, while the other component must be an electrotonic potential. Note that the theoretically expected monophasic positive waveform at the site of collision15 was not seen. Actually, the electrograms recorded from the exact site of collision showed single biphasic potentials.
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From the signal map in Fig 6B, we can see that the two components of the long-double potentials coincide with the two waves at either side of the line of functional conduction block, the interval between the two components being proportional to the time difference in activation at either side. Because in this example the lower wave propagated from right to left, the interval between the two components along the arc of block also progressively increased from right to left (compare the double potentials at the lower right and the upper left of the signal map).
Fig 6C shows the signal map from a pivot point. At the site where the impulse makes a sharp U-turn, the double component electrogram recorded at the line of block (thick line) is replaced by fragmented electrograms consisting of multiple discrete deflections. The various components of the fragmented electrograms at the pivot point coincide with the large single potentials recorded at some distance around the pivot point.
Fig 6D shows a band of fragmented electrograms recorded from an area of slow conduction (6 cm/s between isochrones 60 through 120). The fragmentation of the electrograms was completely functional in nature. Not only were perfectly normal electrograms recorded in the same area during sinus rhythm and rapid atrial pacing, but also most of the complexes recorded from this area consisted of normal single potentials during AF.
Electrogram Morphology During Different Types of AF
As described previously, the activation of the right atrium during AF shows large interindividual differences.2 Fig 7 gives examples of each of the AF types as distinguished on the basis of an increasing degree of complexity of atrial activation. From each patient, a single unipolar electrogram during 4 seconds of AF is shown, together with four activation maps at 1-second intervals. In the diagrams below the maps, the corresponding spatial distribution of the different electrogram morphologies are plotted. During type I AF, the broad fibrillation waves predominantly produced single potential electrograms (indicated by dots). Scattered throughout the atrial wall and varying from beat to beat, some short-double complexes also were recorded (open squares). When two waves collided, short-double potentials were clustered at either side of the line of collision (map 3). However, as can be seen in map 1, some short-double potentials were also found during apparently uniform conduction (see below). The occasional occurrence of short arcs of conduction block (map 2) was associated with the recording of long-double potentials (solid squares). Fragmented electrograms (asterisks) were seen only rarely during type I AF and mostly as isolated spots at various sites. During type II AF (middle), more lines of functional conduction block were present, and the proportion of long-double potentials concomitantly was higher (solid squares). More fragmented electrograms (asterisks) also were recorded because slow conduction and pivoting fibrillation waves were more common during type II AF. During type III AF (bottom), the free wall of the right atrium was activated by multiple fibrillation wavelets that continuously collided, blocked, and pivoted around the ends of lines of block. Areas of slow conduction also were frequently seen, probably because of insufficient recovery of excitability during the short local fibrillation intervals. This complex pattern of activation resulted in a high number of long-double and fragmented potentials (together, 28±6% of all complexes). Because the sites of block, pivot points, and slow conduction continuously changed, the sites where long-double and fragmented potentials were recorded changed from beat to beat. The spatial variation in activation patterns during AF thus is expressed as temporal variations in unipolar electrogram characteristics recorded from a fixed site.
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, single potentials;
Predictive Value of Electrogram Configuration
In Fig 8, the different types of unipolar electrograms recorded for all 25 patients during AF are correlated with the underlying local activation patterns. The database consisted of a total of 517 fibrillation maps comprising more than 115 000 complexes. Of these electrograms, 79±11% were recorded at sites showing uniform fast conduction, 3±2% during collision, 15±8% during conduction block, 2±2% at areas of slow conduction, and 2±1% at pivot points. During broad fast-conducting fibrillation waves, the majority of the recorded electrograms showed a single biphasic configuration (94±4%). However, even during uniform conduction, 5±2% of the electrograms exhibited double potentials (see below). During collision, conduction block, slow conduction, or pivoting, the proportion of single potentials was only 22±13%, 14±7%, 33±27%, and 17±12%, respectively. Collision of wave fronts was characterized by short-double potentials (65±5%). A lower proportion of short-double potentials (15±6%) was found at lines of conduction block when the time difference in activation at either side of the line of block was relatively small (at the ends of the line of block). At arcs of intra-atrial conduction, block long-double potentials prevailed (71±8%). Both during slow conduction and pivoting of fibrillation waves, fragmented potentials were recorded most frequently (58±21% and 80±10%, respectively). Of all recorded fragmented potentials, about half (52±11%) were involved in a pivot point.
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Table 2 gives the sensitivity, specificity, and PPV, and NPV of the electrogram morphology for the underlying pattern of activation. In the first columns, the relative proportion of the electrogram configurations associated with each pattern of activation is listed. As expected, single potentials were highly sensitive (0.95) and specific (0.84) for fast conduction, with a PPV of 0.96. Short-double potentials were most sensitive for collision (0.69). The majority (98±2%) of the long-double potentials recorded during collision of fibrillation waves (13±9%) had a time difference of <20 ms between the two components.
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Long-double potentials were highly sensitive for local conduction block (0.75) with a PPV of 0.84. Fragmented electrograms were highly specific for both slow conduction (0.98) and pivot points (0.99). The sensitivity of fragmented electrograms was higher for pivot points than for slow conduction (0.85 versus 0.61). From the high NPVs of 0.99 and 1.00, one can conclude that in the absence of a fragmented electrogram, the chance of slow conduction or turning of wave fronts is practically zero.
Table 3 summarizes the PPVs of the different fibrillation electrogram morphologies for the various patterns of activation. Whereas single potentials, long-double potentials, and fragmented potentials were clearly indicative of a certain pattern of activation (fast conduction, conduction block, or slow conduction/pivot points), the presence of short-double potentials was about equally predictive for fast conduction, collision, or conduction block (PPVs 0.36, 0.33, and 0.31 respectively). As Fig 9 shows, double potential electrograms recorded during fast conduction exhibited only a small time difference between the two components with a median value of 7 ms. The 90th and 95th percentiles of the time differences between the double potentials during uniform conduction was 11 and 16 ms, respectively. This degree of spatiotemporal dissociation in intra-atrial conduction thus is obviously a normal physiological property of human atria, and short-double potentials should not be considered a sign of abnormal atrial conduction.
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Identification of Areas With Intrinsic Conduction Disturbances
In Fig 10, we have plotted the individual spatial distribution of all multicomponent electrograms (long-double plus fragmented potentials) recorded from the right atrial free wall during 4 seconds of AF. Short-double complexes were not taken into account. At each recording site, the relative percentage of long-double plus fragmented complexes is plotted in a gray scale (white <0.25%; black >2.25%). Patients with documented episodes of AF (indicated by asterisks) did not show an apparent different distribution than the others. During type I AF, the small number of multicomponent electrograms tended to be clustered in certain parts of the mapped area. This is probably due to linking of the activation sequences18 and the relative low number of multicomponent electrograms recorded during type I fibrillation instead of pointing to the presence of areas of impaired conduction. During type II and type III AF, the double and fragmented electrograms were more or less equally distributed over the mapped area, and no preferential areas of conduction block, slow conduction, or pivot points could be detected in the free wall of the right atrium. This was in agreement with the absence in these patients of any functional or structural intra-atrial conduction disturbances during sinus rhythm or rapid atrial pacing.2 Thus, in normal atrial myocardium, the proportion of double and fragmented potentials during electrically induced AF was randomly distributed in space.
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Morphology of Unipolar Electrograms
The waveform of extracellular electrograms recorded during propagation of a depolarization wave in atrial or ventricular myocardium has been shown to depend on many factors, such as the amplitude and upstroke velocity of the action potential, the direction of the wave front relative to the fiber axis (anisotropy), discontinuities in electrical side-to-side coupling between (groups of) fibers, and asynchrony in activation of closely adjacent areas.8 11 The studies of Spach and Dolber11 showed that "complex waveform shapes with multiple deflections...can be interpreted in terms of asynchronous excitation of small groups of fibers within distances of 50 to 100 µm." AF can be considered an experiment by nature in which a constant structure (the atrial myocardium) is subjected to a continuously changing pattern of excitation by multiple wavelets propagating at short coupling intervals and in different directions. Because of the occurrence of functional rate-dependent intra-atrial conduction block, the activation of the atria frequently becomes dissociated, either by turning of wavelets around a line of block or by reentry by another wavelet traveling in a different direction (random reentry). In the present study, the changes in configuration of unipolar fibrillation electrograms caused by this continuous changing dissociation in conduction were studied.
Short-Double Potentials
During sinus rhythm and rapid atrial pacing, 7% to 8% of the unipolar electrograms recorded from the free wall of the right atrium showed double potentials. The sites where these double potentials were recorded were scattered throughout the atrial wall and were not associated with any detectable slowing of the activation wave. Recently, Schuessler et al19 have shown that during normal atrial activation of the canine right atrium, transmural differences in activation time 
24 ms occurred. Therefore the short-double potentials recorded from the epicardium during fast propagation of broad uniform activation waves may reflect the normal physiological dissociation in conduction between the transmural layers of the atrial wall. In the present study, the double potentials recorded from the free wall of the human right atrium during uniform conduction showed a median phase difference between the double components of 6 ms. In 90% and 95% of the cases, the time difference between double potentials recorded during normal conduction was <11 and 16 ms, respectively. Thus, in our opinion, short-double potentials with a dissociation of <10 to 15 ms should be considered normal potentials that express the physiological heterogeneity in the architecture of the atrial wall.
During AF, short-double potentials were also recorded at either side of the lines of collision of fibrillation waves, reflecting a small phase difference between the two waves. At the exact sites of collision, however, biphasic potentials were recorded. This was a somewhat surprising finding, because in other studies single monophasic positive potentials were found at sites of collision.15 This discrepancy may be due to the different preparations used in these studies. Monophasic positive potentials were recorded in thin in vitro preparations in which only the superficial cell layers remain intact. However, if recordings are done from the epicardium of an intact perfused atrium, as in our study and that of Schuessler et al,19 the intramural layers also participate in the generation of epicardial potentials. This may explain why in the intact heart single biphasic potentials were recorded at sites of collision, flanked by dissociated short-double potentials. If at the moment of epicardial collision a depolarization wave is still propagating in deeper layers of the atrial wall, this will generate a far-field potential, causing a negative deflection in the terminal part of the biphasic electrograms recorded from the epicardial line of collision.
Long-Double Potentials
Double potentials were first demonstrated at the central line of block of functionally determined circuits during mapping of rabbit and canine atrial reentry.20 21 Later studies showed that they can also be recorded from anatomic barriers in both the atria and the ventricles.13 14 22 Double-spike electrograms can exist during various tachyarrhythmias, sinus rhythm, or slow pacing.6 7 8 9 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 There is general agreement now that they simply reflect asynchronous activation of tissue at either side of an area of block, regardless of its nature and independent of the presence of reentry.8 9 29 30 31 32 33 34 35 36 37 Measurement of the temporospatial distribution of double potentials during AF may be of value in two different ways. First, the temporal distribution at a fixed recording site may give information about the proportion of conduction block and the degree of fragmentation of the fibrillation waves without the need for high-density mapping of the fibrillatory process. In this way, different types of fibrillation might be defined quantitatively, and the effects of various antifibrillatory drugs could be evaluated. Second, determination of the spatial distribution of double potentials might identify areas that are critical for perpetuation of AF. They may point to either anatomic abnormalities in the atrial wall (in case they occur at fixed sites) or functional electrophysiological inhomogeneities. In this way, double potentials might help to identify atrial areas that are critical for perpetuation of AF.
Fragmented Electrograms
Fractionated or fragmented electrograms have been recorded in both patients with atrial or ventricular arrhythmias and animal models of tachyarrhythmias.5 8 9 10 14 20 21 22 23 24 25 29 30 31 32 33 34 35 36 37 38 39 40 They currently are used to localize critical zones for atrial flutter and ventricular tachycardia.14 24 34 35 38 The mechanism by which fragmented potentials are generated has been studied in detail by Wit and colleagues8 9 41 and Spach and coworkers.11 15 These studies have shown that each component of a fractionated electrogram arises from action potentials in different muscle bundles that are activated out of phase. In isochrone maps, this results in crowding of isochrones.9 Local asynchronous activation can be due to various mechanisms: (1) spatial dispersion in refractory periods, (2) tissue anisotropy resulting in a zigzag course of the propagating depolarizing wave front on a microscopic level owing to a low number of electrical side-to-side connections,11 42 and (3) the presence of insulating collagenous septa between atrial muscle bundles.9 11
Clinical Implications
AF is the most common type of tachycardia with well-known hemodynamic and thromboembolic implications, and new information allowing a possible cure from this arrhythmia is of obvious importance. Mapping studies, including our own, showed the role of reentry in the genesis and perpetuation of AF. These observations led to an interest in approaches that prevent reentry mechanisms from occurring by creating anatomic barriers in the atrial wall. Examples of such approaches are the MAZE operation43 and the creation of lines in the atrium by catheter techniques.44 One of the challenges in dissecting the atrium to cure AF is to make the dissections in such a way that the contractility of the atrium is not seriously impaired. That requires the smallest possible number of dissections preferably in such a direction that synchronized atrial contraction is still possible. To do so, identification of possible critical areas for reentry during AF becomes mandatory.
Although the atria as a whole participate in the process of AF and each cell is reexcited at a high rate by the wandering wavelets, not all parts of the atria contribute equally to the perpetuation of the fibrillatory process. Instead, it seems more likely that the pathophysiological changes associated with aging or an underlying cardiac disease will affect different parts of the atria with a different time course and to a different degree. Although in our study population, patients who had experienced spontaneous episodes of AF showed no differences compared with patients in whom AF did not occur, parts of the atria showing a high proportion of multicomponent potentials in patients with chronic AF might point to structural or functional abnormalities of the myocardium which might play a role in the persistence of atrial fibrillation. As long as the structure of the atria does not show generalized pathological changes, selective ablation of the most seriously affected parts might be of value for the treatment of AF. In light of what is currently known, arcs of intra-atrial conduction block, areas of slow conduction, and pivot points of turning wavelets all seem to be important factors for perpetuation of AF. Lines of conduction block separate the different wavelets and therefore are an index of the degree of fragmentation of activation. Areas of slow conduction shorten the wavelength of the wandering wavelets, thereby increasing the number that can coexist in the atria. Pivot points are crucial because no matter how many wavelets are present, if they do not turn, they will soon die out at the boundaries of the atria and fibrillation will terminate. Our present study shows that all these abnormal conduction patterns (slow conduction, functional conduction block, and pivot points) are "translated" into long-double and fragmented potentials. This offers the possibility of using these potentials recorded during AF as a guide to identify atrial areas eligible for radiofrequency ablation. In the future, selective ablation of such areas might offer an additional approach for the treatment of AF.
Study Limitations
The observations made during induced AF in WPW patients with normal hemodynamics and normally sized atria cannot be considered characteristic of the arrhythmia mechanisms in patients with paroxysmal or chronic AF. We currently are not well informed whether preferential areas for reentry during AF exist in patients with spontaneous and/or persistent AF. If so, we do not know where they are located and whether they are anatomically or functionally determined. It is not unlikely that those areas differ in location and properties in patients with "lone" AF and in patients with AF secondary to atrial enlargement as in mitral valve disease. Also, it is not known whether paroxysmal AF has the same arrhythmogenic mechanism as chronic AF. Because we analyzed only a single episode of AF in each patient and mapping was limited to the right atrial free wall, it remains unclear to what extent temporal or spatial variation in AF and electrogram configuration exists and whether a single sample as analyzed in the present study is representative of the whole process of atrial fibrillation.
For all these reasons, one should be cautious in extrapolating the present data to clinical AF. Although it seems unlikely that the fundamental relationship between the various patterns of activation and the configuration of unipolar atrial electrograms would be basically different, it cannot be excluded that in diseased atria different patterns of activation exist during AF and that atrial electrograms will show a much higher degree of fragmentation because of either depressed action potentials or electrical uncoupling of fibers. Recently, "focal" patterns of activation have been reported in the free wall of the right atrium in some patients with chronic AF.45 Obviously, more mapping data in patients with AF of different origins and duration are needed, especially because such information may be a guide to design optimal dissecting interventions in the atria to cure AF.
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Acknowledgments |
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This study was supported by a grant from the Dutch Ministry of Economic Affairs (STIPT, MTR 89028).
Received June 3, 1996; revision received October 7, 1996; accepted October 23, 1996.
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References |
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Wells JL, Karp RB, Kouchoukos NT, Maclean WAH, James TN, Waldo AL. Characterization of atrial fibrillation in man: studies following open heart surgery. PACE: Pacing Clin Electrophysiol. 1978;1:426-438.[Medline]
[Order article via Infotrieve]
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Konings KTS, Kirchhof CJHJ, Smeets JLRM, Wellens HJJ, Penn OC, Allessie MA. High-density mapping of electrically induced atrial fibrillation in humans. Circulation. 1994;89:1665-1680.
[Abstract/Free Full Text]
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Schoels W, Restivo M, Caref MA, Gough WB, El-Sherif N. Circus movement atrial flutter in canine sterile pericarditis model: activation patterns during entrainment and termination of single-loop reentry in vivo. Circulation. 1991;83:1716-1730.
[Abstract/Free Full Text]
-
Shimizu A, Nozaki A, Rudy Y, Waldo AL. Multiplexing studies of effects of rapid atrial pacing on the area of slow conduction during atrial flutter in canine pericarditis model. Circulation. 1991;83:983-994.
[Abstract/Free Full Text]
-
Cosio FG, Arribas F, Palacios J, Tascon J, Lopez-Gil M. Fragmented electrograms and continuous electrical activity in atrial flutter. Am J Cardiol. 1986;57:1309-1314.[Medline]
[Order article via Infotrieve]
-
Cosio FG, Arribas F, Barbero JM, Kallmeyer C, Goicolea A. Validation of double-spike electrograms as markers of conduction delay or block in atrial flutter. Am J Cardiol. 1988;61:775-780.[Medline]
[Order article via Infotrieve]
-
Kay GN, Epstein AE, Plumb VJ. The region of slow conduction in sustained ventricular tachycardia: direct endocardial recordings and functional characterization in humans. J Am Coll Cardiol. 1988;11:109-117.[Abstract]
-
Gardner PI, Ursell PC, Fenoglio JJ Jr, Wit AL. Electrophysiologic and anatomic basis for fractionated electrograms recorded from healed myocardial infarcts. Circulation. 1985;72:596-611.
[Abstract/Free Full Text]
-
Dillon SM, Allessie MA, Ursell PC, Wit AL. Influences of anisotropic tissue structure on reentrant circuits in the epicardial border zone of subacute canine infarcts. Circ Res. 1988;63:182-206.
[Abstract/Free Full Text]
-
Schalij MJ, Lammers WJEP, Rensma PL, Allessie MA. Anisotropic conduction and reentry in perfused epicardium of rabbit left ventricle. Am J Physiol. 1992;32:H1466-H1478.
-
Spach MS, Dolber PC. Relating extracellular potentials and their derivatives to anisotropic propagation at a microscopic level in human cardiac muscle: evidence for electrical uncoupling of side-to-side fiber connections with increasing age. Circ Res. 1986;58:356-371.
[Abstract/Free Full Text]
-
Spach MS, Dolber PC, Heidlage JF. Interaction of inhomogeneities of repolarization with anisotropic propagation in dog atria. Circ Res. 1989;65:1612-1631.
[Abstract/Free Full Text]
-
Kadish AH, Shinnar M, Moore EN, Levine JH, Balke CW, Spear JF. Interaction of fiber orientation and direction of impulse propagation with anatomic barriers in anisotropic canine myocardium. Circulation. 1988;78:1478-1494.
[Abstract/Free Full Text]
-
Kadish A, Spear J. Identification of conduction block in cardiac muscle: in vitro observations in canine epicardium. Cardiovasc Res. 1994;28:259-269.
[Abstract/Free Full Text]
-
Spach MS, Barr RC, Serwer GA, Johnson EA, Kootsey JM. Collision of excitation waves in the dog Purkinje system: extracellular identification. Circ Res. 1971;29:499-511.
[Abstract/Free Full Text]
-
Allessie MA, Hoeks APG, Schmitz GML, Reneman RS. On-line mapping system for the visualization of the electrical activation of the heart. Int J Cardiac Imag. 1986;2:59-63.[Medline]
[Order article via Infotrieve]
-
Wit AL, Allessie MA, Bonke FIM, Lammers WJEP, Smeets JLRM, Fenoglio JJ Jr. Electrophysiologic mapping to determine the mechanism of experimental ventricular tachycardia initiated by premature impulses: experimental approach and initial results demonstrating reentrant excitation. Am J Cardiol. 1982;49:166-185.[Medline]
[Order article via Infotrieve]
-
Gerstenfeld EP, Sahakian AV, Swiryn SP. Evidence for transient linking of atrial excitation during atrial fibrillation in humans. Circulation. 1992;86:375-382.
[Abstract/Free Full Text]
-
Schuessler RB, Kawamoto T, Hand DE, Mitsuno M, Bromberg BI, Cox JL, Boineau JP. Simultaneous epicardial and endocardial activation sequence mapping in the isolated canine right atrium. Circulation. 1993;88:250-263.
[Abstract/Free Full Text]
-
Allessie MA, Bonke FIM, Schopman FJG. Circus movement in rabbit atrial muscle as a mechanism of tachycardia, III: the `leading circle' concept: a new model of circus movement in cardiac tissue without the involvement of an anatomical obstacle. Circ Res. 1977;41:9-18.
[Free Full Text]
-
Allessie MA, Lammers WJEP, Bonke FIM, Hollen SJ. Intra-atrial reentry as a mechanism for atrial flutter induced by acetylcholine and rapid pacing in the dog. Circulation. 1984;70:123-135.
[Abstract/Free Full Text]
-
Feld GK, Shahandeh-Rad F. Mechanism of double potentials recorded during sustained atrial flutter in the canine right atrial crush-injury model. Circulation. 1992;86:628-641.
[Abstract/Free Full Text]
-
Puech P, Latour H, Grolleau R. Le flutter et ses limites. Arch Mal Coeur. 1970;63:116-144.
-
Josephson ME, Horowitz LN, Spielman SR, Waxman HL, Greenspan AM. Role of catheter mapping in the preoperative evaluation of ventricular tachycardia. Am J Cardiol. 1982;49:207-220.[Medline]
[Order article via Infotrieve]
-
Fontaine G, Guiraudon GM, Frank RGJ. Double epicardial potentials in idiopathic ventricular tachycardia. Circulation. 1976;54:II-78.
-
Werner P-C, Klein H. Sind Dopplepotentiale ein Hinweis fuer Kreisende Erregung? Intraatriales Katheter Mapping bei Vorhofflattern. Z Kardiol. 1990;79:525-540.
-
Olshansky B, Okumura K, Henthorn RW, Waldo AL. Characterization of double potentials in human atrial flutter. Studies during transient entrainment. J Am Coll Cardiol. 1990;15:833-841.[Abstract]
-
Olshansky B, Moreira DAR, Waldo AL. Characterization of double potentials during ventricular tachycardia: studies during transient entrainment. Circulation. 1993;87:373-381.
[Abstract/Free Full Text]
-
Okumura K, Plumb VJ, Page PL, Waldo AL. Atrial activation sequences during atrial flutter in the canine pericarditis model and its effects on the polarity of the flutter wave in the electrocardiogram. J Am Coll Cardiol. 1991;17:509-518.[Abstract]
-
Ortiz J, Igarashi M, Gonzalez X, Johnson NJ, Waldo AL. A new, reliable atrial fibrillation model with a clinical counterpart. J Am Coll Cardiol. 1993;21:183A. Abstract.
-
Boineau JP, Schuessler RB, Mooney CR, Miller CB, Wylds AC, Hudson RD, Borremans JM, Brockus CW. Natural and evoked atrial flutter due to circus movement in dogs: role of abnormal atrial pathways, slow conduction, nonuniform refractory period distribution and premature beats. Am J Cardiol. 1980;45:1167-1181.[Medline]
[Order article via Infotrieve]
-
Durrer D, van Lier AAW, Buller J. Epicardial and intramural excitation in chronic myocardial infarction. Am Heart J. 1964;68:765-776.[Medline]
[Order article via Infotrieve]
-
Waldo AL, Kaiser GA. A study of ventricular arrhythmia associated with acute myocardial infarction in the canine heart. Circulation. 1973;47:1222-1228.
[Abstract/Free Full Text]
-
El-Sherif N, Scherlag BF, Lazzara R, Hope RR. Reentrant arrhythmias in the late myocardial infaction period, I: conduction characteristics in the infarct zone. Circulation. 1977;55:686-702.
[Abstract/Free Full Text]
-
Shimizu A, Nozaki A, Rudy Y, Waldo AL. Characterization of double potentials in a functionally determined reentrant circuit: multiplexing studies during interruption of atrial flutter in the canine pericarditis model. J Am Coll Cardiol. 1993;22:2022-2032.[Abstract]
-
Klein H, Karp RB, Kouchoukos NT, Zorn GL Jr, James TN, Waldo AL. Intraoperative electrophysiologic mapping of the ventricles during sinus rhythm in patients with a previous myocardial infarction: identification of the electrophysiologic substrate of ventricular arrhythmias. Circulation. 1982;66:847-853.
[Free Full Text]
-
Cassidy DM, Vassalle JA, Buxton AE, Doherty JV, Marchlinski FE, Josephson ME. The value of catheter mapping during sinus rhythm to localize site of origin of ventricular tachycardia. Circulation. 1984;69:1103-1110.
[Abstract/Free Full Text]
-
Saoudi N, Atallah G, Kirkorian G, Touboul P. Catheter ablation of the atrial myocardium in human type I atrial flutter. Circulation. 1990;81:762-771.
[Abstract/Free Full Text]
-
Olshansky B, Okumura K, Hess PG, Waldo AL. Demonstration of an area of slow conduction in human atrial flutter. J Am Coll Cardiol. 1990;16:1639-1648.[Abstract]
-
Fontaine G, Guiraudon FR, Tereau Y, Pavie A, Cabrol C, Chomette G, Grosgogeat Y. Surgical management of ventricular tachycardia not related to myocardial ischemia. In: Josephson ME, Wellens HJJ, eds.: Tachycardia: Mechanism, Diagnosis and Treatment. Philadelphia, Pa: Lea & Febiger; 1984:451-473.
-
Ursell PC, Gardner PI, Albala A, Fenoglio JJ Jr, Wit AL. Structural and electrophysiological changes in the epicardial border zone of canine myocardial infarcts during infarct healing. Circ Res. 1985;56:436-451.
[Abstract/Free Full Text]
-
Brugada J, Mont L, Boersma L, Kirchhof C, Allessie A. Differential effects of heptanol, potassium, and tetrodotoxin on reentrant ventricular tachycardia around a fixed obstacle in anisotropic myocardium. Circulation. 1991;84:1307-1318.
[Abstract/Free Full Text]
-
Cox JL, Schuessler RB, D'Agostino HJ, Stone CM, Chang B, Cain ME, Corr PB, Boineau JP. The surgical treatment of atrial fibrillation, III: development of a definitive surgical procedure. J Thorac Cardiavasc Surg. 1991;101:569-583.[Abstract]
-
Swartz JF, Pellersels S, Patten L, Cervantez D. A catheter-based curative approach to atrial fibrillation in humans. Circulation. 1994;90:335. Abstract.
-
Holm M, Johansson R, Olsson SB, Brandt J, Luhrs C. A new method for analysis of atrial activation during chronic atrial fibrillation in man. IEEE Trans Biomed Eng. 1996;43:198-210.[Medline]
[Order article via Infotrieve]
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