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Electroanatomic mapping of right atrial activation in patients with and without paroxysmal atrial fibrillation
Journal of Electrocardiology Vol. 36 No. 3 2003
Electroanatomic Mapping of Right Atrial Activation in Patients With and Without Paroxysmal Atrial Fibrillation
Jijian Luo, MD, Shiwen Yuan, MD, PhD, Eva Hertervig, MD, Ole Kongstad, MD, Erik Ljungstro¨m, MD, Magnus Holm, MSc, PhD, and S. Bertil Olsson, MD, PhD
Abstract: Inter-atrial conduction delay in patients with atrial fibrillation (AF) has been reported. However, the area of this conduction delay has not been well identified. The activation time and conduction velocity over the right atrial endocardium were evaluated during sinus rhythm using the CARTO mapping technique in 6 patients with paroxysmal AF (AF group) and 11 patients without history of AF (control group). No significant differences were observed between the 2 groups in the mean activation times and conduction velocities from the earliest activation site to the superior septum, His bundle area and coronary sinus ostium, or in the total activation times of the right atrium. There was no significant difference between the two groups in the local conduction velocity between 2 adjacent sites in the free wall, septum and bottom of the right atrium. This study suggests the previously reported conduction delay in the posteroseptal region in patients with paroxysmal AF might locate within the posterior inter-atrial septum. Key words: Atrium, activation, conduction velocity, mapping, atrial fibrillation.
Although atrial activation during sinus rhythm has been studied previously (1–3), regional conduction time and conduction velocity are still incompletely understood because of the complexity of atrial anatomical architecture and the limitations of measurement methods. A better understanding of the location and electrophysiological properties of intra- and inter-atrial activation disturbances may
have clinical implications, especially in patients with atrial fibrillation (AF). It has been reported that disturbances of atrial conduction are related to the genesis of this arrhythmia (4 –7). Some studies showed that individuals with clinical histories of atrial dysrhythmias have increased intra-atrial conduction times in response to atrial extrastimuli as compared with normal subjects (6). Platonov et al. (7) in a series of recent studies provided further evidence on the role of atrial conduction disturbance in the genesis of lone AF and suggested that the disturbance localizes between the high lateral right atrium and the proximal coronary sinus (CS). The objective of the present study was to qualitatively and quantitatively analyze the activation times and conduction velocity of the right atrial
From the Department of Cardiology, University Hospital, Lund University, Lund, Sweden; and Biosense Webster Europe, Waterloo, Belgium. Reprint requests: Shiwen Yuan, MD, PhD, Department of Cardiology, University Hospital, SE-221 85, Lund, Sweden; e-mail: [email protected]. © 2003 Elsevier Inc. All rights reserved. 0022-0736/03/3603-0008$30.00/0 doi:10.1016/S0022-0736(03)00031-1
237
238 Journal of Electrocardiology Vol. 36 No. 3 July 2003 endocardium during sinus rhythm in the patients with or without paroxysmal AF using the electroanatomic mapping technique.
in equal areas of 1 to 2 cm2, especially around the CS ostium and the inter-atrial septum. Data Analysis
Materials and Methods Patients The study was performed in 6 patients with paroxysmal AF (mean age 56 ⫾ 12 years, AF group) and 11 patients with atrio-ventricular (AV) nodal re-entrant tachycardia without previous history of AF (mean age 57 ⫾ 12 years, control group). Diagnosis was verified by evaluation of medical history, physical examination, 12-lead ECG, chest X-ray, and transthoracic echocardiography. In AF patients, the mean durations of paroxysmal AF history were 8 ⫾ 3 years (range, 3 to 11 years). All antiarrhythmic medication was terminated at least 5 half-lives before the electrophysiological study. No patient was taking amiodarone 3 months prior to the study. The anteroposterior diameter of the left atrium was measured by two-dimensional echocardiography in the parasternal long-axis view. P-wave duration was measured on the screen from lead II or V1 of the surface ECG recorded with the CARTO system (CARTO; Biosense, Waterloo, Belgium). The study was approved by the local ethical committee and in accordance with the principles outlined in the Declaration of Helsinki. Informed consent was obtained from all patients. Electroanatomic Mapping The electroanatomic mapping system has previously been described in detail (8,9). We used the system for right atrial mapping. All patients were in sinus rhythm with the base line heart rate. Twelvelead ECG was monitored continuously to detect potential changes in cycle length and P-wave morphology. Mapping started under fluoroscopy and continued under the guidance of real-time, threedimensional maps on the screen of the CARTO system. A bipolar atrial electrogram from the middle of the CS was taken as the time reference to calculate local activation time. Anatomic landmarks of the superior and inferior vena cava, the CS ostium, the His bundle area and tricuspid annulus were identified, and tagged on the maps (Fig. 1). The bottom of the right atrium was defined as the area bounded by the tricuspid annulus, the CS ostium, and the inferior vena cava. Care was taken to acquire mapping points
After visual inspection, and if necessary, manual correction of the activation time at each point and deletion of points with wrong time reference or premature beats, an activation map was obtained for data analysis. At each point, the local activation time was set at the maximum value of the first sharp deflection of the bipolar electrogram. Qualitative analysis of the activation patterns of the right atrium was performed by identifying the earliest and latest activation areas and the preferential conduction routes to the superior septum, His bundle area and CS ostium. Color coded, three-dimensional activation sequence maps were reconstructed, with the red colour identifying the earliest activation area and the purple the latest (Fig. 1). For quantitative analysis, the following regional activation times were measured with the CARTO system: 1) from the earliest activation site to the CS ostium, 2) from the earliest activation site to the superior septum, 3) from the earliest activation site to the His bundle area, 4) from the earliest activation site at the superior septum to the CS ostium, and 5) the total activation time of the right atrium. The diameters of the right atrium were measured as the maximum value along the X and Z-axes in anteroposterior and right lateral views on the CARTO maps, with the mean of these two measurements being used as the size of the right atrium for data analysis. Direct linear distance between 2 given points could be provided by the CARTO system. To measure the distance along the preferential route of wave front propagation over the endocardial surface, rather than the direct linear distance, we calculated the distances from the earliest activation site to the superior septum, His bundle area and CS ostium in 3 to 4 segments. The sum of the distances was used for calculating the regional conduction velocity (Fig. 1). Local conduction velocities between randomly selected adjacent sites in areas of the free wall, the bottom, and the septum of the right atrium were also calculated. Statistical Analysis The measurement values were presented as mean⫾standard deviation. Paired or unpaired Student’s T tests were used to compare the means. A value of P ⬍.05 was considered as statistically significant.
Right Atrial Activation in Patients With and Without Atrial Fibrillation •
Luo et al. 239
Fig. 1. Isochronal activation maps of the right atrium from a control patient (left panel), and a patient with paroxysmal atrial fibrillation (right panel), about 15 degrees rightwards (upper) and leftwards (lower) from the posteroanaterior view. Colour-coded isochronal activation sequences are shown, with red identifying the earliest and the latest activation areas in purple. The distance from the earliest activation site to the coronary sinus ostium (CS os) is calculated as the sum of 3-4 segments (see the black arrow lines) along the preferential activation routes. The values on these arrow lines indicate the distance of each segment in millimeters. Total distance ⫽ 73 mm, activation time ⫽ 58 ms, conduction velocity ⫽ 1.26 mm/ms for the control patient (left panel), and total distance ⫽ 88 mm, activation time ⫽ 71 ms and conduction velocity ⫽ 1.24 mm/ms for the patient with atrial fibrillation. His ⫽ His bundle area.
Results The Size of the Atria The size of the left atrium (Table 1) measured by echocardiography was significantly longer in patients with paroxysmal AF, as compared with that in the
control patients (P⬍.05). There was no statistically significant difference in the size of the right atrium measured on the CARTO maps. The mean distance between the superior septum and the CS ostium was not significantly different between the 2 groups. The P wave was significantly longer in patients with paroxysmal AF as compared to the control group.
240 Journal of Electrocardiology Vol. 36 No. 3 July 2003 Table 1. Sizes of the Atria and Duration of the P Wave
Left atrium (mm) Right atrium (mm) P-wave duration (ms)
AF Group (n ⫽ 6)
Control Group (n ⫽ 11)
44 ⫾ 8* 55 ⫾ 10 120 ⫾ 18†
38 ⫾ 5 52 ⫾ 7 101 ⫾ 9
both groups. The mean distances between the superior septum and the CS ostium were not significantly different in the 2 groups, neither were the conduction velocities from the superior septum to the CS ostium (Tables 1 and 2 and Fig. 1). Regional conduction velocities from the earliest activation site to the His bundle area, superior septum and CS ostium showed no statistically significant difference between the two groups (Table 2). The local conduction velocity between 2 adjacent sites in all the 17 patients was markedly slower in the bottom area than that in the septum, with the highest velocity in the free wall (Table 3). However, no statistically significant differences between the 2 groups were found in the local conduction velocity.
*P ⬍ .05 and †P ⬍ .01, as compared with the control group.
Activation Patterns of the Right Atrium Right atrial mapping was performed during sinus rhythm at 59 ⫾ 21 and 67 ⫾ 23 sites in patients with and without paroxysmal AF, respectively. In all patients the area of the earliest activation was located in the upper part of the lateral right atrium corresponding to the location of the sinus node (Fig. 1). Two wave fronts with opposite directions originated from the sinus node area, with the major one progressing along the lateral wall and the septum, while the minor one activating upwards to the superior vena cava. In the AF group, the activation ended at the low lateral right atrium in 2 patients and at the CS ostium in 4 patients, while in the control group, the latest activation was at the CS ostium in 3 patients and at the low lateral aspect in 8 patients. In all patients, the sinus impulse propagated from the superior to the inferior septum.
Discussion Disturbances of atrial conduction have repeatedly been correlated to the occurrence and/or perpetuation of AF, even if AF focal origin (4 – 6,10). In addition, most of the available data were obtained during programmed stimulation in animal models (1,3) or humans (4 –7), while little information exists during sinus rhythm. Regional activation patterns of the atrium and especially the conduction velocity have not been clearly delineated. To our knowledge, the propagation of sinus impulse under pathophysiological conditions such as in the patients with paroxysmal AF has not been described.
Activation Times and Conduction Velocities of the Right Atrium The mean activation times from the earliest site to the His bundle area, superior septum and the CS ostium are presented in Table 2. There were no statistically significant differences in these values between the two groups. Total activation time of the right atrium in the patient with paroxysmal AF was similar to that in the control group. The activation time from the earliest site to the superior septum was shorter than that to the CS ostium in
Methodology The previously reported studies on the conduction disturbances in animal models (1,3) and patients (4 –7,11) with AF were merely activation time measurements based on recordings from mul-
Table 2. Regional Activation Time and Conduction Velocity of the Right Atrium AF Group (n ⫽ 6)
Earliest to CS os Earliest to His bundle area Earliest to superior septum Superior septum to CS os Total right atrium
Control Group (n ⫽ 11)
Activation time (ms)
Velocity (mm/ms)
Activation Time (ms)
Velocity (mm/ms)
74 ⫾ 26 53 ⫾ 13 24 ⫾ 11* 51 ⫾ 15 83 ⫾ 18
1.14 ⫾ 0.27 1.40 ⫾ 0.36 1.29 ⫾ 0.71 1.18 ⫾ 0.17 —
75 ⫾ 17 59 ⫾ 17 31 ⫾ 16* 54 ⫾ 21 90 ⫾ 23
1.09 ⫾ 0.17 1.22 ⫾ 0.30 1.07 ⫾ 0.47 1.21 ⫾ 0.30 —
Earliest, the earliest activation site; CS os, the coronary sinus ostium. *P ⬍ .01 compared with that from the earliest site to the CS ostium.
Right Atrial Activation in Patients With and Without Atrial Fibrillation • Table 3. Local Conduction Velocity Between 2 Adjacent Sites in Different Areas (mm/ms)
Free wall Septum Bottom
AF Group (n ⫽ 6)
Control Group (n ⫽ 11)
All Patients (n ⫽ 17)
1.37 ⫾ 0.22*† 1.19 ⫾ 0.17* 0.57 ⫾ 0.10
1.47 ⫾ 0.20*† 1.24 ⫾ 0.26* 0.56 ⫾ 0.13
1.44 ⫾ 0.21*† 1.22 ⫾ 0.23* 0.57 ⫾ 0.12
*P ⬍ .01 compared with the bottom; †P ⬍ .05 compared with the septum.
tiple electrode catheters and used the high or low right atrial pacing and programmed stimulation. These studies were therefore limited by the interindividual variations in catheter location and size of the atrium. The introduction of the electroanatomic mapping technique CARTO provided a tool for accurate spatial localization of the endocardial recordings (8,9). A limitation of the CARTO system is that only direct linear distance between two sites is available and that this linear distance is used for calculation of the conduction velocity. The distance between 2 remote sites would then be shorter than the true distance over the endocardial surface, and thereby conduction velocity is underestimated. To minimize the influence of the algorithm of distance measurement, we measured the regional conduction velocity by summing the lengths of a series of short straight-line distances over the surface of the right atrial endocardium. In addition, the distance was calculated along the preferential route of impulse propagation, rather than the shortest distance. In this way, the regional conduction velocity obtained in this study was more accurate as compared to that measured directly between 2 remote sites. Prior research has suggested that the specifics of atrial anatomy are critically important in determining the spread of the activating wave front (12). To minimize the influence of the complexity of the right atrial anatomy on our measurement of the regional conduction velocity, we also measured the local conduction velocities between two adjacent sites in the free wall, the bottom and the septal area. The local conduction velocity in the bottom of the right atrium, especially through the so-called tricuspid-inferior vena cava “isthmus” area is known to be a slow zone (13,14). In this study, the conduction velocity of this area was mean 0.57 ⫾ 0.12 mm/ms in all the patients, markedly slower than that in the septum and free wall of the right atrium. This result may further support the validity of our measurement method for different conduction velocities, despite the negative findings in comparison of conduction velocity between our 2 groups. Note-
Luo et al. 241
worthy, the CS ostium area was activated by a downward wave front from the superior septum in all our patients and therefore the slow conduction in the bottom of the right atrium did not influence the activation times and conduction velocities measured in this study. Localization of Atrial Conduction Delay in Patients With AF As mentioned above, intra- and inter-atrial conduction delay has been correlated with spontaneous recurrence or induction of AF (4 – 6,15). However, the localization of this conduction delay has not been well identified. Platonov et al. (7) found that the activation time from the high lateral right atrium to the proximal CS was prolonged in patients with lone paroxysmal AF, as compared with that in patients with AV nodal tachycardia. However, their data did not allow a clarification whether the conduction delay is in the right atrium, in the posteroseptal region, or both. In the current study, we measured the activation times from the earliest activation site to the His bundle area, superior septum and CS ostium during sinus rhythm. Total activation time of the right atrium in our patients was similar to that previously observed in patients with relatively normal hearts (2). No statistically significant difference in these time intervals was found between patients with paroxysmal AF and those with AV nodal tachycardia in our study. In addition, there were no statistically significant differences in the conduction velocities between the above-mentioned areas and between adjacent sites in the local areas. It is worth mentioning that our comparison of the conduction velocity ruled out the influence of inter-individual variations in recording sites and the size of the right atrium, and thereby gave more reliable result of comparison. Our measurement of the atrial size using echocardiography and anatomic maps using the CARTO technique demonstrated that the size of the right atrium in patients with paroxysmal AF was not different from that in patients with AV nodal tachycardia, although the P-wave duration was longer and the left atrium was larger in the former group. This lends a further support to the negative findings in our activation time comparison between these 2 groups. Our findings are not consistent with a study which reported the conduction time between the high lateral right atrium and the proximal coronary sinus is prolonged in patients with paroxysmal AF (7), which may indirectly suggest that the previously reported conduction
242 Journal of Electrocardiology Vol. 36 No. 3 July 2003 delay in patients with paroxysmal AF was in the posteroseptal region between the right atrial endocardium and the proximal coronary sinus.
3.
Study Limitations The activation mapping has only been performed in the right atrium in the present study. A combined right and left atrial mapping could probably provide direct evidence on conduction delay in the posteroseptal region, and warrants a further study. Secondly, the CARTO system provides only direct linear distance and therefore the conduction velocity obtained in this study was only relatively accurate, although we tried to measure the distance in 3 to 4 segments and along the preferential conduction route. However, our results comparing the activation time and conduction velocity between the 2 groups are reliable, since the same algorithm and measurement method were used for both groups.
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Summary Electroanatomic mapping of the right atrium was performed during sinus rhythm in patients with paroxysmal AF and those without history of AF. Activation time and regional conduction velocity from the earliest site to the His bundle area, superior septum and CS ostium have been analysed. No significant differences in these parameters were observed between the 2 groups. The size of the right atrium as measured from the CARTO maps was not significantly different between the 2 groups. Our findings may indirectly suggest that the previously reported conduction delay between the high lateral right atrium and the proximal CS in patients with paroxysmal AF locates in the posterior inter-atrial septum.
References 1. Sun H, Velipasaoglu EO, Wu DE, Kopelen HA, et al: Simultaneous multisite mapping of the right and the left atrial septum in the canine intact beating heart. Circulation 100:312, 1999 2. De Ponti R, Ho SY, Salerno-Uriarte JA, et al: Electroanatomic analysis of sinus impulse propagation in
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normal human atria. J Cardiovasc Electrophysiol 13:1-10, 2002 Derakhchan K, Li D, Courtemanche M, et al: Method for simultaneous epicardial and endocardial mapping of in vivo canine heart: Application to atrial conduction properties and arrhythmia mechanism. J Cardiovasc Eletrophysiol 12:548, 2001 Cosio FG, Palacios J, Vidal JM, et al: Electrophysiological studies in atrial fibrillation. Slow conduction of premature impulses: A possible manifestation of the background for reentry. Am J Cardiol 51:112, 1983 Papageorgiou P, Monahan K, Boyle NG, et al: Sitedependent intra-atrial conduction delay relationship to initiation of atrial fibrillation. Circulation 94:384, 1996 Buxton AE, Waxman HL, Marchlinski FE, et al: Atrial conduction: Effects of extrastimuli with and without atrial dysrhythmias. Am J Cardiol 54:755, 1984 Platonov P, Yuan S, Hertervig E, et al: Further evidence of localized posterior interatrial conduction delay in lone paroxysmal atrial fibrillation. Europace 3:100, 2001 Gepstein L, Hayam G, Ben-Haim SA: A novel method for nonfluoroscopic catheter-based electroanatomical mapping of the heart. In vitro and in vivo accuracy results. Circulation 95:1611, 1997 Riothinger FX, Cheng J, Sippens Groenewegen A, et al: Use of electroanatomic mapping to delineate transseptal atrial conduction in humans. Circulation 100:1791, 1999 Schmitt C, Ndrepepa G, Weber S, et al: Biatrial multisite mapping of atrial premature complexes triggering onset of atrial fibrillation. Am J Cardiol 89:1381, 2002 Roithinger FX, Abou-harb M, Pachinger O, et al: The effect of the atrial pacing site on the total atrial activation time. PACE 24:316, 2001 Lesh MD, Kalman JM, Olgin JE, et al: The role of atrial anatomy in clinical atrial arrhythmias. J Electrocardiol 29:101, 1996 Schilling RJ, Peters NS, Goldberger J, et al: Characterization of the anatomy and conduction velocities of the human right atrial flutter circuit determined by noncontact mapping. J Am Coll Cardiol 38:385, 2001 Tai CT, Chen SA, Chiang CE, et al: Characterization of low right atrial isthmus as the slow conduction zone and pharmacological target in typical atrial flutter. Circulation 96:2601, 1997 Saksena A, Giorgberidze I, Mehra R, et al: Electrophysiology and endocardial mapping of induced atrial fibrllation in patients with spontaneous atrial fibrillation. Am J Cardiol 83:187, 1999
Electroanatomic Mapping of Right Atrial Activation in Patients With and Without Paroxysmal Atrial Fibrillation
Jijian Luo, MD, Shiwen Yuan, MD, PhD, Eva Hertervig, MD, Ole Kongstad, MD, Erik Ljungstro¨m, MD, Magnus Holm, MSc, PhD, and S. Bertil Olsson, MD, PhD
Abstract: Inter-atrial conduction delay in patients with atrial fibrillation (AF) has been reported. However, the area of this conduction delay has not been well identified. The activation time and conduction velocity over the right atrial endocardium were evaluated during sinus rhythm using the CARTO mapping technique in 6 patients with paroxysmal AF (AF group) and 11 patients without history of AF (control group). No significant differences were observed between the 2 groups in the mean activation times and conduction velocities from the earliest activation site to the superior septum, His bundle area and coronary sinus ostium, or in the total activation times of the right atrium. There was no significant difference between the two groups in the local conduction velocity between 2 adjacent sites in the free wall, septum and bottom of the right atrium. This study suggests the previously reported conduction delay in the posteroseptal region in patients with paroxysmal AF might locate within the posterior inter-atrial septum. Key words: Atrium, activation, conduction velocity, mapping, atrial fibrillation.
Although atrial activation during sinus rhythm has been studied previously (1–3), regional conduction time and conduction velocity are still incompletely understood because of the complexity of atrial anatomical architecture and the limitations of measurement methods. A better understanding of the location and electrophysiological properties of intra- and inter-atrial activation disturbances may
have clinical implications, especially in patients with atrial fibrillation (AF). It has been reported that disturbances of atrial conduction are related to the genesis of this arrhythmia (4 –7). Some studies showed that individuals with clinical histories of atrial dysrhythmias have increased intra-atrial conduction times in response to atrial extrastimuli as compared with normal subjects (6). Platonov et al. (7) in a series of recent studies provided further evidence on the role of atrial conduction disturbance in the genesis of lone AF and suggested that the disturbance localizes between the high lateral right atrium and the proximal coronary sinus (CS). The objective of the present study was to qualitatively and quantitatively analyze the activation times and conduction velocity of the right atrial
From the Department of Cardiology, University Hospital, Lund University, Lund, Sweden; and Biosense Webster Europe, Waterloo, Belgium. Reprint requests: Shiwen Yuan, MD, PhD, Department of Cardiology, University Hospital, SE-221 85, Lund, Sweden; e-mail: [email protected]. © 2003 Elsevier Inc. All rights reserved. 0022-0736/03/3603-0008$30.00/0 doi:10.1016/S0022-0736(03)00031-1
237
238 Journal of Electrocardiology Vol. 36 No. 3 July 2003 endocardium during sinus rhythm in the patients with or without paroxysmal AF using the electroanatomic mapping technique.
in equal areas of 1 to 2 cm2, especially around the CS ostium and the inter-atrial septum. Data Analysis
Materials and Methods Patients The study was performed in 6 patients with paroxysmal AF (mean age 56 ⫾ 12 years, AF group) and 11 patients with atrio-ventricular (AV) nodal re-entrant tachycardia without previous history of AF (mean age 57 ⫾ 12 years, control group). Diagnosis was verified by evaluation of medical history, physical examination, 12-lead ECG, chest X-ray, and transthoracic echocardiography. In AF patients, the mean durations of paroxysmal AF history were 8 ⫾ 3 years (range, 3 to 11 years). All antiarrhythmic medication was terminated at least 5 half-lives before the electrophysiological study. No patient was taking amiodarone 3 months prior to the study. The anteroposterior diameter of the left atrium was measured by two-dimensional echocardiography in the parasternal long-axis view. P-wave duration was measured on the screen from lead II or V1 of the surface ECG recorded with the CARTO system (CARTO; Biosense, Waterloo, Belgium). The study was approved by the local ethical committee and in accordance with the principles outlined in the Declaration of Helsinki. Informed consent was obtained from all patients. Electroanatomic Mapping The electroanatomic mapping system has previously been described in detail (8,9). We used the system for right atrial mapping. All patients were in sinus rhythm with the base line heart rate. Twelvelead ECG was monitored continuously to detect potential changes in cycle length and P-wave morphology. Mapping started under fluoroscopy and continued under the guidance of real-time, threedimensional maps on the screen of the CARTO system. A bipolar atrial electrogram from the middle of the CS was taken as the time reference to calculate local activation time. Anatomic landmarks of the superior and inferior vena cava, the CS ostium, the His bundle area and tricuspid annulus were identified, and tagged on the maps (Fig. 1). The bottom of the right atrium was defined as the area bounded by the tricuspid annulus, the CS ostium, and the inferior vena cava. Care was taken to acquire mapping points
After visual inspection, and if necessary, manual correction of the activation time at each point and deletion of points with wrong time reference or premature beats, an activation map was obtained for data analysis. At each point, the local activation time was set at the maximum value of the first sharp deflection of the bipolar electrogram. Qualitative analysis of the activation patterns of the right atrium was performed by identifying the earliest and latest activation areas and the preferential conduction routes to the superior septum, His bundle area and CS ostium. Color coded, three-dimensional activation sequence maps were reconstructed, with the red colour identifying the earliest activation area and the purple the latest (Fig. 1). For quantitative analysis, the following regional activation times were measured with the CARTO system: 1) from the earliest activation site to the CS ostium, 2) from the earliest activation site to the superior septum, 3) from the earliest activation site to the His bundle area, 4) from the earliest activation site at the superior septum to the CS ostium, and 5) the total activation time of the right atrium. The diameters of the right atrium were measured as the maximum value along the X and Z-axes in anteroposterior and right lateral views on the CARTO maps, with the mean of these two measurements being used as the size of the right atrium for data analysis. Direct linear distance between 2 given points could be provided by the CARTO system. To measure the distance along the preferential route of wave front propagation over the endocardial surface, rather than the direct linear distance, we calculated the distances from the earliest activation site to the superior septum, His bundle area and CS ostium in 3 to 4 segments. The sum of the distances was used for calculating the regional conduction velocity (Fig. 1). Local conduction velocities between randomly selected adjacent sites in areas of the free wall, the bottom, and the septum of the right atrium were also calculated. Statistical Analysis The measurement values were presented as mean⫾standard deviation. Paired or unpaired Student’s T tests were used to compare the means. A value of P ⬍.05 was considered as statistically significant.
Right Atrial Activation in Patients With and Without Atrial Fibrillation •
Luo et al. 239
Fig. 1. Isochronal activation maps of the right atrium from a control patient (left panel), and a patient with paroxysmal atrial fibrillation (right panel), about 15 degrees rightwards (upper) and leftwards (lower) from the posteroanaterior view. Colour-coded isochronal activation sequences are shown, with red identifying the earliest and the latest activation areas in purple. The distance from the earliest activation site to the coronary sinus ostium (CS os) is calculated as the sum of 3-4 segments (see the black arrow lines) along the preferential activation routes. The values on these arrow lines indicate the distance of each segment in millimeters. Total distance ⫽ 73 mm, activation time ⫽ 58 ms, conduction velocity ⫽ 1.26 mm/ms for the control patient (left panel), and total distance ⫽ 88 mm, activation time ⫽ 71 ms and conduction velocity ⫽ 1.24 mm/ms for the patient with atrial fibrillation. His ⫽ His bundle area.
Results The Size of the Atria The size of the left atrium (Table 1) measured by echocardiography was significantly longer in patients with paroxysmal AF, as compared with that in the
control patients (P⬍.05). There was no statistically significant difference in the size of the right atrium measured on the CARTO maps. The mean distance between the superior septum and the CS ostium was not significantly different between the 2 groups. The P wave was significantly longer in patients with paroxysmal AF as compared to the control group.
240 Journal of Electrocardiology Vol. 36 No. 3 July 2003 Table 1. Sizes of the Atria and Duration of the P Wave
Left atrium (mm) Right atrium (mm) P-wave duration (ms)
AF Group (n ⫽ 6)
Control Group (n ⫽ 11)
44 ⫾ 8* 55 ⫾ 10 120 ⫾ 18†
38 ⫾ 5 52 ⫾ 7 101 ⫾ 9
both groups. The mean distances between the superior septum and the CS ostium were not significantly different in the 2 groups, neither were the conduction velocities from the superior septum to the CS ostium (Tables 1 and 2 and Fig. 1). Regional conduction velocities from the earliest activation site to the His bundle area, superior septum and CS ostium showed no statistically significant difference between the two groups (Table 2). The local conduction velocity between 2 adjacent sites in all the 17 patients was markedly slower in the bottom area than that in the septum, with the highest velocity in the free wall (Table 3). However, no statistically significant differences between the 2 groups were found in the local conduction velocity.
*P ⬍ .05 and †P ⬍ .01, as compared with the control group.
Activation Patterns of the Right Atrium Right atrial mapping was performed during sinus rhythm at 59 ⫾ 21 and 67 ⫾ 23 sites in patients with and without paroxysmal AF, respectively. In all patients the area of the earliest activation was located in the upper part of the lateral right atrium corresponding to the location of the sinus node (Fig. 1). Two wave fronts with opposite directions originated from the sinus node area, with the major one progressing along the lateral wall and the septum, while the minor one activating upwards to the superior vena cava. In the AF group, the activation ended at the low lateral right atrium in 2 patients and at the CS ostium in 4 patients, while in the control group, the latest activation was at the CS ostium in 3 patients and at the low lateral aspect in 8 patients. In all patients, the sinus impulse propagated from the superior to the inferior septum.
Discussion Disturbances of atrial conduction have repeatedly been correlated to the occurrence and/or perpetuation of AF, even if AF focal origin (4 – 6,10). In addition, most of the available data were obtained during programmed stimulation in animal models (1,3) or humans (4 –7), while little information exists during sinus rhythm. Regional activation patterns of the atrium and especially the conduction velocity have not been clearly delineated. To our knowledge, the propagation of sinus impulse under pathophysiological conditions such as in the patients with paroxysmal AF has not been described.
Activation Times and Conduction Velocities of the Right Atrium The mean activation times from the earliest site to the His bundle area, superior septum and the CS ostium are presented in Table 2. There were no statistically significant differences in these values between the two groups. Total activation time of the right atrium in the patient with paroxysmal AF was similar to that in the control group. The activation time from the earliest site to the superior septum was shorter than that to the CS ostium in
Methodology The previously reported studies on the conduction disturbances in animal models (1,3) and patients (4 –7,11) with AF were merely activation time measurements based on recordings from mul-
Table 2. Regional Activation Time and Conduction Velocity of the Right Atrium AF Group (n ⫽ 6)
Earliest to CS os Earliest to His bundle area Earliest to superior septum Superior septum to CS os Total right atrium
Control Group (n ⫽ 11)
Activation time (ms)
Velocity (mm/ms)
Activation Time (ms)
Velocity (mm/ms)
74 ⫾ 26 53 ⫾ 13 24 ⫾ 11* 51 ⫾ 15 83 ⫾ 18
1.14 ⫾ 0.27 1.40 ⫾ 0.36 1.29 ⫾ 0.71 1.18 ⫾ 0.17 —
75 ⫾ 17 59 ⫾ 17 31 ⫾ 16* 54 ⫾ 21 90 ⫾ 23
1.09 ⫾ 0.17 1.22 ⫾ 0.30 1.07 ⫾ 0.47 1.21 ⫾ 0.30 —
Earliest, the earliest activation site; CS os, the coronary sinus ostium. *P ⬍ .01 compared with that from the earliest site to the CS ostium.
Right Atrial Activation in Patients With and Without Atrial Fibrillation • Table 3. Local Conduction Velocity Between 2 Adjacent Sites in Different Areas (mm/ms)
Free wall Septum Bottom
AF Group (n ⫽ 6)
Control Group (n ⫽ 11)
All Patients (n ⫽ 17)
1.37 ⫾ 0.22*† 1.19 ⫾ 0.17* 0.57 ⫾ 0.10
1.47 ⫾ 0.20*† 1.24 ⫾ 0.26* 0.56 ⫾ 0.13
1.44 ⫾ 0.21*† 1.22 ⫾ 0.23* 0.57 ⫾ 0.12
*P ⬍ .01 compared with the bottom; †P ⬍ .05 compared with the septum.
tiple electrode catheters and used the high or low right atrial pacing and programmed stimulation. These studies were therefore limited by the interindividual variations in catheter location and size of the atrium. The introduction of the electroanatomic mapping technique CARTO provided a tool for accurate spatial localization of the endocardial recordings (8,9). A limitation of the CARTO system is that only direct linear distance between two sites is available and that this linear distance is used for calculation of the conduction velocity. The distance between 2 remote sites would then be shorter than the true distance over the endocardial surface, and thereby conduction velocity is underestimated. To minimize the influence of the algorithm of distance measurement, we measured the regional conduction velocity by summing the lengths of a series of short straight-line distances over the surface of the right atrial endocardium. In addition, the distance was calculated along the preferential route of impulse propagation, rather than the shortest distance. In this way, the regional conduction velocity obtained in this study was more accurate as compared to that measured directly between 2 remote sites. Prior research has suggested that the specifics of atrial anatomy are critically important in determining the spread of the activating wave front (12). To minimize the influence of the complexity of the right atrial anatomy on our measurement of the regional conduction velocity, we also measured the local conduction velocities between two adjacent sites in the free wall, the bottom and the septal area. The local conduction velocity in the bottom of the right atrium, especially through the so-called tricuspid-inferior vena cava “isthmus” area is known to be a slow zone (13,14). In this study, the conduction velocity of this area was mean 0.57 ⫾ 0.12 mm/ms in all the patients, markedly slower than that in the septum and free wall of the right atrium. This result may further support the validity of our measurement method for different conduction velocities, despite the negative findings in comparison of conduction velocity between our 2 groups. Note-
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worthy, the CS ostium area was activated by a downward wave front from the superior septum in all our patients and therefore the slow conduction in the bottom of the right atrium did not influence the activation times and conduction velocities measured in this study. Localization of Atrial Conduction Delay in Patients With AF As mentioned above, intra- and inter-atrial conduction delay has been correlated with spontaneous recurrence or induction of AF (4 – 6,15). However, the localization of this conduction delay has not been well identified. Platonov et al. (7) found that the activation time from the high lateral right atrium to the proximal CS was prolonged in patients with lone paroxysmal AF, as compared with that in patients with AV nodal tachycardia. However, their data did not allow a clarification whether the conduction delay is in the right atrium, in the posteroseptal region, or both. In the current study, we measured the activation times from the earliest activation site to the His bundle area, superior septum and CS ostium during sinus rhythm. Total activation time of the right atrium in our patients was similar to that previously observed in patients with relatively normal hearts (2). No statistically significant difference in these time intervals was found between patients with paroxysmal AF and those with AV nodal tachycardia in our study. In addition, there were no statistically significant differences in the conduction velocities between the above-mentioned areas and between adjacent sites in the local areas. It is worth mentioning that our comparison of the conduction velocity ruled out the influence of inter-individual variations in recording sites and the size of the right atrium, and thereby gave more reliable result of comparison. Our measurement of the atrial size using echocardiography and anatomic maps using the CARTO technique demonstrated that the size of the right atrium in patients with paroxysmal AF was not different from that in patients with AV nodal tachycardia, although the P-wave duration was longer and the left atrium was larger in the former group. This lends a further support to the negative findings in our activation time comparison between these 2 groups. Our findings are not consistent with a study which reported the conduction time between the high lateral right atrium and the proximal coronary sinus is prolonged in patients with paroxysmal AF (7), which may indirectly suggest that the previously reported conduction
242 Journal of Electrocardiology Vol. 36 No. 3 July 2003 delay in patients with paroxysmal AF was in the posteroseptal region between the right atrial endocardium and the proximal coronary sinus.
3.
Study Limitations The activation mapping has only been performed in the right atrium in the present study. A combined right and left atrial mapping could probably provide direct evidence on conduction delay in the posteroseptal region, and warrants a further study. Secondly, the CARTO system provides only direct linear distance and therefore the conduction velocity obtained in this study was only relatively accurate, although we tried to measure the distance in 3 to 4 segments and along the preferential conduction route. However, our results comparing the activation time and conduction velocity between the 2 groups are reliable, since the same algorithm and measurement method were used for both groups.
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Summary Electroanatomic mapping of the right atrium was performed during sinus rhythm in patients with paroxysmal AF and those without history of AF. Activation time and regional conduction velocity from the earliest site to the His bundle area, superior septum and CS ostium have been analysed. No significant differences in these parameters were observed between the 2 groups. The size of the right atrium as measured from the CARTO maps was not significantly different between the 2 groups. Our findings may indirectly suggest that the previously reported conduction delay between the high lateral right atrium and the proximal CS in patients with paroxysmal AF locates in the posterior inter-atrial septum.
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