Cardiovascular Research

Cardiovascular Research 2002 54(2):217-229; doi:10.1016/S0008-6363(01)00549-1
© 2002 by European Society of Cardiology

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Copyright © 2002, European Society of Cardiology

Mechanisms of atrial flutter and atrial fibrillation: distinct entities or two sides of a coin?

Albert L. Waldo^*

Division of Cardiology, Department of Medicine, MS 5038, University Hospitals of Cleveland/Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5038, USA

^* Tel.: +1-216-844-7690; fax: +1-216-844-7196 alw2{at}po.cwru.edu

Received 17 September 2001; accepted 12 November 2001

KEYWORDS Arrhythmia (mechanisms); Conduction (block); Impulse formation; Mapping; Supraventricular arrhythmia

	1 Introduction

Top 1 Introduction 2 The mechanism of... 3 Components of the... 4 Importance of atrial... 5 Reentrant circuits and... 6 Summary and conclusions Acknowledgments References

 
There has been a long recognized clinical interrelationship between atrial flutter and atrial fibrillation. Patients who primarily manifest atrial flutter commonly also experience atrial fibrillation and vice versa [1,2]. Both are very common as a temporary atrial tachyarrhythmia shortly after open heart surgery, and often in the same patient [3]. And some antiarrhythmic agents, notably class IC drugs, IA drugs and amiodarone, used to suppress atrial fibrillation not uncommonly ‘convert’ recurrences of atrial tachyarrhythmia to atrial flutter [4–6]. Are these clinical associations mere coincidences, or do they reflect an important underlying similar pathophysiology and even similar mechanism(s)? Data derived largely from a series of unconnected studies in animal models and patients seemingly point to a clear interrelationship between the two, suggesting, if not indicating, that they are two sides of a coin.

Classical atrial flutter, now called typical and reverse typical atrial flutter [7], is well recognized to be due to a macro-reentrant mechanism, in which the reentrant wave front travels up the inter-atrial septum and down the right atrial free wall or vice versa, respectively [1,7]. Critical to the development and maintenance of this reentrant circuit are the lateral boundaries, one being fixed (anatomic), the tricuspid valve annulus, and the other almost always being functional, a line of block between the venae cavae. We shall develop the theme that one of the fundamental features that determines whether an atrial tachyarrhythmia becomes sustained atrial flutter or atrial fibrillation is the development of the line of block between the venae cavae. We shall also develop the theme that another of the fundamental features that determine whether the atrial tachyarrhythmia becomes atrial flutter or atrial fibrillation often will be the atrial flutter cycle length, i.e. the cycle length of a stable atrial reentrant circuit which develops. If it is critically short, it will create fibrillatory conduction and clinical atrial fibrillation; if it is sufficiently long, it will result in 1:1 activation of the atria by the reentrant circuit, with resulting clinical atrial flutter. Critical to the latter consideration is the increasing recognition that atrial flutter may be due to macroreentrant circuits which are different than that responsible for typical and reverse typical atrial flutter [8–11].

	2 The mechanism of classical atrial flutter—the importance of block between the venae cavae

Top 1 Introduction 2 The mechanism of... 3 Components of the... 4 Importance of atrial... 5 Reentrant circuits and... 6 Summary and conclusions Acknowledgments References

 
On the basis of studies in experimental animals and on vector analysis of electrocardiograms in humans, Lewis and colleagues [12] concluded that atrial flutter was the result of circus movement in the atria. Their experimental studies included mapping (quite limited) of induced atrial flutter in normal canine atria (Fig. 1) [12]. From these studies, Lewis and colleagues [12] concluded that atrial flutter was due to reentry around their great veins. But Lewis had great difficulty inducing atrial flutter in the model [12]. We now think that was because in the normal canine heart, the normal atrial substrate failed to develop a line of block between the superior and inferior vena cava which seems necessary for the development of stable atrial flutter [13]. The latter appears to have been recognized in 1947 by Rosenblueth and Garcia-Ramos [14], who created a crush lesion between the venae cavae in canine atria, and then were reliably able to induce atrial flutter (Fig. 2). Of note, in both the former models and most subsequent models, atrial flutter was induced by rapid atrial pacing which, very likely in some or with certainty in others, first induced atrial fibrillation.

View larger version (30K): [in this window] [in a new window] [Download PowerPoint slide]   Fig. 1 "An accurate and natural-sized outline of the auricle of dog KQ showing the readings obtained during the period of flutter. These have been reduced to a new common 0. The broken arrows represent the path pursued by the excitation wave, as ascertained from the direction of the deflection in direct leads and from the surface recordings; the former and latter evidences were entirely confirmatory of each other. An area is shaded to display the pericardial reflection more prominently." I.V.C., inferior vena cava; P.V., pulmonary veins; S.V.C., superior vena cava. S marks the point stimulated. From Lewis et al. [12].

 

View larger version (32K): [in this window] [in a new window] [Download PowerPoint slide]   Fig. 2 This figure is from the work of Kimura et al. [15], who repeated the work of Rosenblueth and Garcia-Ramos [14] by creating a lesion between the venae cavae (obliquely hatched area) with Pean's forceps. The relative sequence of atrial activation at ten sites during induced atrial flutter is indicated by the lines with arrows. I.V.C., inferior vena cava; l.App., left atrial appendage; P.V., pulmonary veins; r.App., right atrial appendage; S.V.C., superior vena cava. From Rytand [16].

 
More recently, it was shown in canine atria that, in the presence of an intercaval lesion similar to those of Rosenblueth and Garcia-Ramos plus an extension of the lesion towards the right atrial appendage, thereby creating a Y lesion, induced atrial flutter is due to circus movement around the tricuspid valve annulus (Fig. 3) [17,18]. As recognized by Frame et al. [17,18], the Y lesion they created provided boundaries that both limited the atrial reentrant circuit to the tricuspid ring and also protected the reentrant circuit from being short circuited. The latter is important for the development of any stable reentrant circuit. We shall see how block between the venae cavae seems to have a critical role in the pathogenesis of classical atrial flutter in other models and in patients, with the Y lesion being a variant of the kind of block necessary for the development of stable atrial flutter.

View larger version (29K): [in this window] [in a new window] [Download PowerPoint slide]   Fig. 3 This is a diagram of the heart viewed from the right posterior oblique projection showing the location of the Y-shaped lesion between the vena cavae and in the right atrial free wall to create the model for tricuspid ring reentrant atrial flutter. The intercaval lesion extends from the superior vena cava to the inferior vena cava and the other lesion extends from the intercaval lesion across the right atrium toward the right atrial appendage. Each number indicates the position of a bipolar pair of electrodes. In this model, induced atrial flutter produced either clockwise or counterclockwise reentrant activation around the tricuspid valve annulus. LA, left atrial appendage; RA, right atrial appendage. From Frame et al. [17].

 
The intercaval region is not the only location where a sufficiently long line of block can provide a critical substrate for reentrant atrial flutter. Thus, other canine right atrial lesion models have been developed [19–21] in which the lesion provides a line of block around which the reentrant wave front travels. Moreover, this mechanism of atrial flutter now has been documented in patients after repair of congenital heart defects that involve one or more right atrial free wall incisions [22–24], but until recently, the mechanism was not understood. However, our group [25] has now shown in the normal canine heart that a sufficiently long lesion in the right atrial free wall may develop a functional extension of the line of fixed block to one or both of the venae cavae (Fig. 4). When that occurs, the atrial flutter mechanism is that of typical or reverse typical atrial flutter, i.e. the reentrant wave front travels up the septum and down the right atrial free wall or vice versa. The latter is of particular interest and relevance in that we [26] and others [22–24] have recently shown that most cases of atrial flutter which occur chronically in patients following open heart surgical repair of congenital heart disease use the classical atrial flutter reentrant circuit. We suggest that this is a clinical counterpart of the latter canine studies. Thus, in most of these patients, rather than the reentrant wave front circulating around the line of block created during the surgical repair, the atrial flutter reentrant wave front most often travels up the atrial septum and down the right atrial free wall, or vice versa, and the reentrant circuit includes the so-called atrial flutter isthmus between the inferior vena cava, the Eustachian ridge, the coronary sinus ostium and the tricuspid annulus. This occurs because a line of block, in this case part fixed (anatomic) from the surgical incision and part functional, is present between the venae cavae.

View larger version (30K): [in this window] [in a new window] [Download PowerPoint slide]   Fig. 4 (Left panel) Activation map during induced atrial flutter (cycle length 134 ms). The thick black line indicates the line of fixed block due to creation of a lesion. The hatched areas indicate functional extension of the line of fixed block. The atrial flutter reentrant circuit travels up the right atrial free wall (arrow) and down the atrial septum (dashed arrow), with epicardial breakthrough in the peri-inferior vena caval region (white asterisk) and septal entry at Bachmann's bundle (black asterisk). IVC, inferior vena cava; LAA, left atrial appendage; PV, pulmonary veins; RAA, right atrial appendage; SVC, superior vena cava; a–d are recording sites from which electrograms are shown in the right panel. (Right panel) Electrograms a–d were recorded from sites a–d shown in the left panel. The double potentials in electrograms b and c correspond to the potentials recorded in electrograms a and d, and indicate that a line of block exists between sites a and d during atrial flutter that was not present during sinus rhythm or atrial pacing. From Tomita et al. [25].

 
We have chronologically just jumped ahead of the story to develop the theme. But it is well to continue to develop the story chronologically. Major advances in understanding the mechanism of atrial flutter occurred when improved mapping resolution became available with use of simultaneous multisite recording techniques, the latter employing ever larger numbers of electrodes. Some, but not all the studies demonstrated that atrial flutter was associated with a line of block between the venae cavae. Studies of the acetylcholine infusion model by Allessie et al. [27,28] in a Langendorff preparation of the canine heart showed that atrial flutter due to intra-atrial reentry can occur superiorly or inferiorly in either atrium, and can even occur in the absence of an anatomic obstacle (Fig. 5). In the latter studies, the atrial flutter cycle lengths were often quite short. In the example shown (Fig. 5), four of the six reentrant circuits had a cycle length of 115 ms or less. In those cases, 1:1 atrial activation to the remainder of the atria rather that fibrillatory conduction was possible only because of the presence of the acetylcholine. We shall see shortly the possible or probable relevance of these studies to atrial fibrillation. Several other models of atrial flutter in the canine heart have also shown a reentrant circuit independent of an anatomic obstacle, including a spontaneous example of atrial flutter in a single dog studied by Boineau et al. [29], a right atrial enlargement model secondary to creation of tricuspid regurgitation and pulmonary artery banding by Boyden and Hoffman [30,31], and the sterile pericarditis model of atrial flutter described by our laboratory [32] and studied by us [33–38] and others [39,40]. In each of these latter three experimental models, the reentrant circuit is confined to the right atrium. Mapping of a canine model of mitral regurgitation described by Cox et al. [41] has shown several reentrant circuits, including one resulting from reentry confined to the right atrium in which the reentrant circuit had no anatomical obstacle.

View larger version (18K): [in this window] [in a new window] [Download PowerPoint slide]   Fig. 5 Demonstration of the location and direction of circus movement in six examples of atrial flutter induced in a canine acetylcholine infusion model of atrial flutter. Atrial flutter cycle lengths from the right and left atrial appendage reentrant circuits were 100 and 115 ms, respectively. Atrial flutter cycle length from the inferior right atrial reentrant circuit was 100 ms. Atrial flutter cycle length from the postero-inferior left atrial reentrant circuit near the inferior vena cava was 65 ms. Atrial flutter cycle lengths from the left atrial free wall reentrant circuits were 130 and 145 ms in two such examples. From Allessie et al. [28].

 
A limitation of most of the above described experimental studies is that minimal or no mapping of the intraatrial septum was performed. However, Boyden's studies, which included mapping of the atrial septum, demonstrated that the septum sometimes was involved in the reentrant circuit [31,42]. The initial sequential site mapping studies of the sterile pericarditis model also suggested that the atrial septum sometimes might be involved [33]. However, the recent studies in the sterile pericarditis model by Uno et al. [43], who recorded systematically from the atrial septum, showed that the reentrant atrial flutter circuit involved the atrial septum either as part of a single loop reentrant circuit, or as part of a figure-of-eight reentry. In single loop reentry, a functional line of block is present in the region between the venae cavae (Fig. 6). In figure-of-eight reentry, the functional line of block is just more anterior and does not connect to either of the venae cavae, but is still critical to the development of stable atrial flutter (Fig. 7) [43]. Finally, a model of atrial flutter associated with reentry around a lesion produced by detaching and reanastomosing the pulmonary veins was demonstrated by Ghandi et al. in a canine model [44] and in patients [45].

View larger version (49K): [in this window] [in a new window] [Download PowerPoint slide]   Fig. 6 Representative examples of activation maps during sustained atrial flutter (AFL) in the canine sterile pericarditis model due to a single reentrant circuit. (Top panel) Activation map (atrial epicardium, left; atrial septum, right) from an episode of sustained AFL demonstrating a single reentrant circuit (black) in which the reentrant circuit travels down the atrial septum and up the right atrial free wall. (Bottom panel) Activation map (atrial epicardium, left; atrial septum, right) from an episode in a different study of sustained AFL demonstrating a single reentrant circuit (black) in which the reentrant circuit travels up the atrial septum and down the right atrial free wall. In these activation maps, arrows indicate direction of activation of various wave fronts, light gray arrows indicate daughter wave fronts generated by the reentrant circuit, isochrones are at 10-ms intervals, thick dashed line indicates line of functional block, gray asterisk indicates epicardial breakthrough of septal activation, white asterisk indicates site of reentry from epicardium to atrial septum, and T bars indicate block. Numbers indicate activation time in milliseconds. IVC, inferior vena cava; PV, pulmonary veins; SVC, superior vena cava. Letters a–h are sites from which selected bipolar atrial electrograms were exhibited in the originally published figure. See text for discussion. Modified from Uno et al. [43].

 

View larger version (50K): [in this window] [in a new window] [Download PowerPoint slide]   Fig. 7 Representative examples of activation maps during sustained atrial flutter (AFL) induced in the canine sterile pericarditis model due to figure-of-eight reentry. (Top panel) Activation map (atrial epicardium, left; atrial septum, right) from one study demonstrating figure-of-eight reentry in which the right atrial free wall reentrant circuit (dotted pattern) circulates in a counterclockwise direction, and the reentrant circuit involving the atrial septum (black) travels down the interatrial septum and up the right atrial free wall. a–m indicate recording sites of bipolar electrograms exhibited in the originally published figure. (Bottom panel) Activation map (atrial epicardium, left; atrial septum, right) from another study demonstrating figure-of-eight reentry in which the right atrial free wall reentrant circuit (dotted pattern) circulated in a clockwise direction, and the reentrant circuit involving the atrial septum (black) traveled up the interatrial septum to Bachmann's bundle and then down the right atrial free wall. See text for discussion. Modified from Uno et al. [43].

 

	3 Components of the atrial flutter reentrant circuit in patients and their locations

Top 1 Introduction 2 The mechanism of... 3 Components of the... 4 Importance of atrial... 5 Reentrant circuits and... 6 Summary and conclusions Acknowledgments References

 
Contemporary mapping studies of atrial flutter in humans have further refined our understanding of the usual reentrant circuit in atrial flutter. Thus, studies using standard catheter electrode mapping techniques, entrainment pacing techniques, intra-atrial echocardiography, and three-dimensional mapping techniques have better defined and characterized the classical atrial flutter reentrant circuit. It includes a boundary located in an isthmus between the tricuspid valve annulus on one side and the Eustachian ridge and coronary sinus ostium on the other side [46–50]. It also includes another boundary, either or both the superior vena cava and the inferior vena cava, and a line of block located between them in the region of the crista terminalis [46,48–53]. This is the same region that has been recognized as critical to the formation of stable atrial flutter in most animal models [13–19,29,31,33,34,37–39,42,43,54,55] including, retrospectively, even the studies of Lewis et al. [12]. Cosio et al. [56–58], who first emphasized block in this area during atrial flutter in patients, considered that it was functional block. Although data from Lesh's group [48,49] were interpreted as showing that this region of block is fixed (anatomic) in patients with atrial flutter, others have continued to show that block in this region is functional [59–61]. What is clear is that block in this region is very important to understanding the pathogenesis of typical and reverse typical atrial flutter [13], the most common forms of clinical atrial flutter. In this regard, we suggest that when an antiarrhythmic drug ‘converts’ atrial fibrillation to classical atrial flutter, it is because it has facilitated development of a functional line of block between the venae cavae.

It should be mentioned for completeness that, as recently summarized [13], there is a history of studies which were interpreted as showing that atrial flutter was due to a single focus firing rapidly. This mechanism as an explanation of atrial flutter has not stood the test of time. While it is possible that some unusual cases of atrial flutter may be due to a single focus firing rapidly, it certainly has not been clinically recognized with any frequency, if at all.

	4 Importance of atrial fibrillation to the pathogenesis of atrial flutter—its role in the development of functional block between the venae cavae

Top 1 Introduction 2 The mechanism of... 3 Components of the... 4 Importance of atrial... 5 Reentrant circuits and... 6 Summary and conclusions Acknowledgments References

 
As summarized recently [62], the requisites for the initiation of a reentrant rhythm have been well understood for a long time, and have been well described. There must be a tissue substrate capable of supporting the reentrant excitation; there must be an area of block around which the reentrant wave front can circulate; and the initiating excitation wave front must encounter an area of unidirectional block to generate the reentrant excitation. Furthermore, the reentrant circuit usually has one or more areas of slow conduction. The best understood and characterized reentrant rhythm has been atrioventricular (AV) reentrant tachycardia (i.e. AV reentrant excitation associated with the presence of an accessory AV connection). In this latter rhythm, a premature beat initiates the arrhythmia immediately (i.e. there is no preceding transitional rhythm). This occurs because there is a complete reentrant circuit waiting to be engaged. The initiating premature beat encounters unidirectional block at a critical location in the tissue substrate that comprises the reentry circuit. This unidirectional block occurs either in the accessory AV connection or in the specialized AV conduction system. By a similar mechanism, the premature beat that initiates AV nodal reentrant tachycardia also initiates this reentrant rhythm immediately. The same is not usually true for typical and reverse typical atrial flutter. Most often, typical and reverse typical atrial flutter do not start immediately after a premature beat. Rather, they first go through a transitional rhythm of atrial fibrillation, as demonstrated by studies of induced and spontaneous onset of atrial flutter (Fig. 8) [34,38,63–65].

View larger version (27K): [in this window] [in a new window] [Download PowerPoint slide]   Fig. 8 The two tracings in each panel are continuous, and show ECG lead II recorded simultaneously with a bipolar right atrial electrogram (AEG). In the top panel, the asterisk denotes a premature atrial beat which induced atrial fibrillation. In the middle panel, the atrial fibrillation continues until atrial flutter develops at the asterisk. In the bottom panel, the stable atrial flutter continues. Time lines represent 1-s intervals. From Waldo and Cooper [64].

 
Insights into the reason why atrial fibrillation seems most often to precede the initiation of reentrant atrial flutter are provided by studies in animal models. We have already seen that in the canine heart, a line of block is required between the superior and inferior venae cavae to achieve a stable equivalent of typical or reverse typical atrial flutter [14–19,29,31,33,34,37,39–43,54,55], but this line of block normally is not present. As mapping studies in the canine sterile pericarditis model [34] and right atrial enlargement model [42] have shown, it is during the induced transitional rhythm that the critical line of functional block first develops in the right atrial free wall, completing a necessary boundary between the venae cavae (Fig. 9). With establishment of this boundary, unidirectional block then occurs, and stable atrial flutter becomes established. Without the development of this functional component of the atrial flutter reentrant circuit, atrial fibrillation either persists or spontaneously converts back to sinus rhythm. The important point is that it is during the transitional rhythm of atrial fibrillation that the last requisites for reentrant atrial flutter develop. There is otherwise no atrial flutter reentrant substrate waiting to be engaged. We suggest that the same function is probably served by the transitional atrial fibrillation at the onset of atrial flutter in patients. One, in fact, could conclude that in most instances, without atrial fibrillation, there is no atrial flutter.

View larger version (34K): [in this window] [in a new window] [Download PowerPoint slide]   Fig. 9 Isochronous maps from the right atrial free wall during the onset of figure-of-eight atrial flutter in the canine sterile pericarditis model induced by an eight-beat drive train (S1) followed by two premature beats (S2 and S3, respectively) (300/130/80 ms) delivered from the right atrial appendage (RAA). Isochrones are displayed at 10-ms intervals. Arrows indicate the direction of the main activation wave front. (Top panel) Beats A1, A2 and A3 are isochronous maps corresponding to S1, S2 and S3, respectively. Beat A1 (S1) was the last driven beat at a cycle length of 300 ms. Beat A2 (S2) was the first premature beat. Beat A3 (S3) was the second premature beat. In beats A2 and A3, radial activation proceeded from the pacing site, and crowding of 10-ms isochronous lines developed in some areas. In beat A4, the first spontaneous (Spont) beat, the earliest activated area was close to the pacing site. (Bottom panel) Beats A5–A8 represent subsequent spontaneous beats. Beats A5 and A6 show development of the areas of slow conduction along the epicardial aspect of the region of the crista terminalis and in the pectinate muscle region. With beat A7, unidirectional block (UB) (solid thick black line) of the inferior wave front occurred at the pectinate muscle region in the area of slow conduction. Then, the non-blocked superior activation wave front traveled around a line of functional block present in the epicardial aspect of the region of the crista terminalis (dashed lines) and through an area of slow conduction close to the inferior vena cava to conduct through the area of unidirectional block from the opposite direction. The shaded area represents an area of localized block. Beat A8 was the first spontaneous atrial flutter beat (cycle length of 152 ms). AV groove, atrioventricular groove; IVC, inferior vena cava; RAA, right atrial appendage; S, site of stimulation; SVC, superior vena cava; UB, unidirectional block. Modified from Shimizu et al. [34].

 
What happens during the instances when a brief period of atrial fibrillation does not appear to precede the onset of atrial flutter? This may have more than one explanation. One may be related to physiologic variability, in that some patients may have a very high degree of block or complete block already present in the region between the venae cavae [48,49]. Another may be that when atrial flutter is initiated by atrial pacing with an eight beat drive train at a 300-ms cycle length (200 bpm) followed by one or two premature beats introduced at a short cycle length, functional block may form in the intercaval region during the period of pacing. Unfortunately, the available studies during the onset of induced atrial flutter in patients have not yet produced systematic activation maps from the intercaval area. Additional studies are needed to resolve this question fully.

Further evidence for the importance, in fact, the necessity of the line of functional block in the right atrium to permit the maintenance of stable atrial flutter comes from mapping studies during spontaneous and ATP-induced conversion of atrial flutter to atrial fibrillation in the canine sterile pericarditis model [38]. In these studies, the conversion of atrial flutter to atrial fibrillation was associated with a shortening of the length of the line of functional block from a mean of 24±4 mm to a mean of 16±3 mm. This shortened line of block continued to change while migrating over the right atrial free wall during the period of atrial fibrillation. In these studies, stable atrial flutter returned when there was reformation of a sufficiently long line of block (i.e. prior length) in the right atrial free wall that reestablished the boundary between the venae cavae necessary to permit and protect stable atrial flutter.

	5 Reentrant circuits and atrial fibrillation—the role of fibrillatory conduction

Top 1 Introduction 2 The mechanism of... 3 Components of the... 4 Importance of atrial... 5 Reentrant circuits and... 6 Summary and conclusions Acknowledgments References

 
Moe and Abildskov [66] proposed the multiple reentrant wavelet hypothesis as the mechanism of atrial fibrillation. Their subsequent computer model supported this mechanism [67], and later, sophisticated mapping studies of induced atrial fibrillation in a canine, Langendorff perfused, acetylcholine infusion model by Allessie et al. [27,68] demonstrated this mechanism. But while the multiple reentrant wavelet mechanism may be an important mechanism of atrial fibrillation, it is noteworthy that most subsequent studies in animal models and patients have not found this mechanism to be operative. Rather, they have found fibrillatory conduction (i) from a single, stable reentrant circuit of very short cycle length [69,70]; (ii) from multiple, unstable reentrant circuits of very short cycle length [71]; or (iii) from a single focus of very short cycle length [72]. Schuessler et al. [73] in an in vitro canine right atrial preparation superfused with acetylcholine demonstrated that a single figure-of-eight reentrant circuit of very, very short cycle length (45 ms) drove the rest of the preparation producing fibrillatory conduction (Fig. 10). Subsequent studies of Skanes et al. in sheep atria [69] and Matsuo et al. [70] in the sterile pericarditis model have shown that a single stable reentrant circuit, primarily in the left atrium, can drive the atria so fast that the atrial tissue cannot follow 1:1, i.e. fibrillatory conduction results (Fig. 11). In short, single reentrant circuits (if you will, a very fast atrial flutter) can cause atrial fibrillation.

View larger version (37K): [in this window] [in a new window] [Download PowerPoint slide]   Fig. 10 Atrial fibrillation induced in a canine right atrial preparation in the presence of 10–4.5 M acetylcholine. Under each map is the beginning and end time of each window. The black dots indicate selected recording sites from amongst 250 bipolar electrodes. Isochrones are at 10-ms intervals. The sixth, seventh and eighth cycles are shown. Note that a small figure-of-eight reentrant circuit of very, very short cycle length (39–48 ms) is driving the preparation with fibrillatory conduction. From Schuessler et al. [73].

 

View larger version (82K): [in this window] [in a new window] [Download PowerPoint slide]   Fig. 11 Isochrone maps and pseudo-EGs constructed from left atrial (LA) and right atrial (RA) optical recordings of an episode of atrial fibrillation. (A) Isochrone map of single rotation of stable rotor located in the left atrium. (B) Pseudo-EG of this signal, which is monomorphic. (C) Two sequential RA isochrone maps during atrial fibrillation. RA pseudo-EG is shown in (D). Despite uniform LA activation, RA activation is highly heterogeneous in both activation sequence (see isochrone maps) and electrical activity (see pseudo-EG). The bipolar EG seen in (E) is consistent with atrial fibrillation.

 
That this might happen in patients has already been suggested by the data from Waldo and Cooper in post open heart surgical patients (Fig. 12) [64]. And limited, simultaneous, multisite mapping studies during open heart surgery in patients with rapid pacing induced atrial fibrillation by Cox et al. [74] and Konings et al. [75] have demonstrated unstable reentrant circuits of very short cycle length in the right atrium (Figs. 13 and 14). This is consistent with the possibility that, as in the animal models of Skanes et al. [69] and Matsuo et al. [70], they generated fibrillatory conduction and, thereby, clinical atrial fibrillation. And the recent findings of more left atrial flutter reentrant circuits and atypical atrial flutter in the right atrium (upper loop reentry, lower loop reentry) [8–11] all suggest that stable reentry (atrial flutter) due to a number of mechanisms is possible. Indeed, it is really intuitive that a spectrum of atrial flutters based on rate is possible if not likely, and that when the rate is too fast, fibrillatory conduction and clinical atrial fibrillation result. And again, atypical, stable atrial reentrant circuits are beginning to be found in patients as mapping gets more sophisticated. It is of interest that the group from Mexico City considered that reentry could occur around one of the pulmonary veins or one of the venae cavae, but that the calculated cycle length would be too short to explain clinical trial flutter [76]. Implicit in this is that such reentrant circuits could cause atrial fibrillation via fibrillatory conduction.

View larger version (51K): [in this window] [in a new window] [Download PowerPoint slide]   Fig. 12 (Top panel) ECG lead II recorded simultaneously with bipolar atrial electrograms from the sulcus terminalis (STEG) and Bachmann's bundle (BBEG). * Indicates a premature atrial beat that induces Type II atrial flutter at a rate of 390 bpm. As is evident from the ECG lead, the very rapid rate of the Type II atrial flutter rate produces atrial fibrillation. We suggest this occurs because the atrial tissue cannot respond in a 1:1 manner to the very rapid rate of the Type II atrial flutter. In other words, the Type II atrial flutter drives the atria, fibrillatory conduction results, and the ECG demonstrates atrial fibrillation. Time lines at 1-s intervals. (Bottom panel) ECG lead II recorded simultaneously with bipolar atrial electrograms from the sulcus terminalis (STEG) and Bachmann's bundle (BBEG) continuous with the tracings in the top panel. * Indicates initiation of typical atrial flutter. Type II atrial flutter persists at the recording sites as does atrial fibrillation in the ECG, until, as denoted by the asterisk, typical atrial flutter abruptly develops. We suggest that during the period of atrial fibrillation generated by the Type II atrial flutter, the functional components of the typical atrial flutter reentrant circuit evolved. Time lines are at 1-s intervals. From Waldo and Cooper [64].

 

View larger version (35K): [in this window] [in a new window] [Download PowerPoint slide]   Fig. 13 A right atrial reentrant circuit during induced human atrial fibrillation is shown. In this example, the rotation of the reentrant wave front is clockwise. The length of the window is 400 ms, with the activation from the first 210 ms shown in the left map, and 210–400 ms shown in the right map. IVC, inferior vena cava; LAA, left atrial appendage; M, mitral valve; PV, pulmonary veins; RAA, right atrial appendage; SVC, superior vena cava; T, tricuspid valve. Modified after Cox et al. [74].

 

View larger version (36K): [in this window] [in a new window] [Download PowerPoint slide]   Fig. 14 Leading circle reentry, one of two different types of reentry described by Konings et al. [75] in their limited mapping study of induced atrial fibrillation in patients undergoing surgical ablation of an accessory atrioventricular (A-V) connection (W-P-W syndrome). The two left panels show the reentrant wave front circulating around a shifting central line of functional block. The right panel shows the unipolar atrial electrograms recorded from the sites indicated by circled numbers on the maps. Modified after Konings et al. [75].

 

	6 Summary and conclusions

Top 1 Introduction 2 The mechanism of... 3 Components of the... 4 Importance of atrial... 5 Reentrant circuits and... 6 Summary and conclusions Acknowledgments References

 
The fact that patients frequently have both atrial flutter and atrial fibrillation is well established clinically, and suggests a mechanistic interaction. The major such interaction, we suggest, is that atrial fibrillation is usually required for the development of a line of functional block between the venae cavae, which, in turn, is required for the development of classical atrial flutter. A second major interaction, we suggest, is that when a stable atrial flutter of very short cycle length develops, it will cause fibrillatory conduction and, thereby, maintain atrial fibrillation. We do not mean to suggest that the latter mechanism is the only cause of atrial fibrillation, as it certainly is not. However, we do believe it is probably an important mechanism of atrial fibrillation, and perhaps the most common form of atrial fibrillation, at least at its inception. But without a doubt, there is a clear interaction between atrial fibrillation and atrial flutter. They are at least kissing cousins, and commonly may be responsible for causing each other. In that sense, at the very least, they are certainly two sides of a coin.

Time for primary review 23 days.

	Acknowledgments

Top 1 Introduction 2 The mechanism of... 3 Components of the... 4 Importance of atrial... 5 Reentrant circuits and... 6 Summary and conclusions Acknowledgments References

 
This research was supported in part by Grant RO1 HL38408 from the United States Public Health Service, National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda, MD.

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