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Contact Electroanatomic Mapping Derived Voltage Criteria for Characterizing Left Atrial Scar in Patients Undergoing Ablation for Atrial Fibrillation SURAJ KAPA, M.D.,∗ BENOIT DESJARDINS, M.D., Ph.D.,† DAVID J. CALLANS, M.D.,∗ FRANCIS E. MARCHLINSKI, M.D.,∗ and SANJAY DIXIT, M.D.∗ From the ∗ Division of Cardiac Electrophysiology, Department of Medicine; and †Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
Voltage Criteria for Left Atrial Scar. Background: Criteria have not been established for identifying LA scar using electroanatomic mapping (EAM). It is also unclear if voltage criteria using EAM may assist in identifying areas of pulmonary vein (PV) reconnection in patients undergoing repeat AF ablation. Objectives: To characterize left atrial (LA) voltage in patients undergoing atrial fibrillation (AF) ablation. Methods: An LA shell was created and bipolar voltage amplitude (in mV) at each point was measured. The shell was divided into 8 regions. Bipolar voltage values lower than the amplitude of 95% of sampled points was used as the upper cutoff value. Delayed enhancement (DE) cardiac magnetic resonance imaging (CMRI) sequences were performed to validate voltage cutoffs. Results: Twenty patients participated. A mean of 141 ± 12 points constituted the LA map that was created during sinus rhythm (SR). In patients undergoing initial AF ablation, mean bipolar LA voltage was 1.44 ± 1.27 mV. In patients undergoing repeat AF ablation, scar along the posterior wall and LA–PV junction was identified using a voltage cutoff 0.2 mV, whereas for other LA locations 95% of points demonstrated signal amplitude >0.45 mV.
TABLE 1
Characteristic
Voltage Criteria for Left Atrial Scar
58 ± 6 8 (80%) 8 (80%) 2 (20%) 2 (20%) 1 (10%) 1 (10%) 2 (20%) 57 ± 12 4.4 ± 0.9 4 (40%) 6 (60%) 5 (50%) 5 (50%) 3 (30%)
63 ± 10 6 (60%) 6 (60%) 1 (10%) 0 (0%) 0 (0%) 2 (20%) 0 (0%) 61 ± 9 4.0 ± 0.5 6 (60%) 4 (40%) 10 (100%) 3 (30%) 3 (30%)
61 ± 9 14 (70%) 14 (70%) 3 (15%) 2 (10%) 5 (5%) 3 (15%) 2 (10%) 59 ± 11 4.2 ± 0.7 10 (50%) 10 (50%) 15 (75%) 8 (40%) 6 (30%)
6 (60%)
5 (50%)
11 (55%)
Results Patient Population A total of 20 patients comprised the study cohort (paroxysmal AF in 12 [60%]). Patient characteristics are detailed in Table 1. Ten subjects were undergoing their first ablation procedure and 10 subjects were undergoing repeat AF ablation. In subjects undergoing repeat ablation, the initial procedure was antral PVI alone in 8 (80%), and in 2 patients, additional MA, and LA roof lines were performed. Voltage Characterization in Patients Undergoing Initial AF Ablation A mean of 141 ± 12 points per patient constituted the LA map in this group. Approximately 63% of these points (89 ± 10) were located in the PV antrum including the posterior LA, adjoining septum, roof, and anterior ridge. The overall bipolar voltage of the LA in this group of patients was 1.44 ± 1.27 mV. The LA floor manifested the highest mean voltages (1.70 ± 1.25 mV), whereas LA–PV junction had the lowest mean voltages (1.02 ± 1.25 mV; Table 2). Table 3 summarizes the bipolar voltage cutoff value, which was below the amplitude of 95% of the points sampled in each anatomic segment. Specifically for the posterior wall and LA–PV junc-
Voltage Characterization in Patients with Prior Left Atrial Ablation Table 4 summarizes the regional voltage distribution in this group of patients. Since all patients in this group had undergone prior antral PVI, as expected, the lowest mean bipolar voltages were found in the posterior wall (0.51 ± 0.62 mV) and LA–PV junction (0.23 ± 0.32 mV) and these were significantly reduced as compared with other LA regions (P < 0.01 for both the LA–PV and posterior wall compared with other regions). Among all the LA regions, only the LA–PV junction and posterior wall showed lower mean amplitude in patients undergoing repeat AF ablation as compared to patients undergoing initial AF ablation (P < 0.01 for LA–PV junction and posterior wall, NS for other regions, Fig. 4). In the patients undergoing repeat AF ablation (n = 10), using voltage settings of 0.2–0.45 mV (established from analysis of bipolar voltage information in patients with sinus rhythm undergoing initial AF ablation), scar was clearly identified around the PVs (Fig. 5A). Furthermore, in PVs showing evidence of electrical reconnection, we were also able to demonstrate segmental areas of relatively preserved voltage around the LA–PV junction. A total of 17 segments at the LA–PV junction of reconnected veins demonstrated preserved voltages and their distribution was as follows: septal aspect of the right PVs in 6 patients, posterior roof bordering right PVs in 6 patients, anterior ridge of the left PVs in 2 patients and the posterior aspect of left PVs in 3 patients. The mean signal amplitude of these segments with preserved voltages was 0.9 ± 0.2 mV (range 0.32–1.3 mV) and none of the points in these reconnected segments demonstrated a voltage < 0.3 mV (Fig. 6). During reisolation of these veins, a mean of 9 ± 5 lesions were required to traverse these segments with preserved voltages (Fig. 5B). Of note, in all chronically isolated PVs, DE abnormality in a circumferential distribution was seen on the MRI study at the time of repeat ablation. DE-MRI-Voltage Mapping Correlation Preprocedure CMRI studies were performed in 12 of the 20 study patients (60%; 6 undergoing initial ablation and 6 undergoing repeat ablation). None of the subjects
TABLE 2 Average Voltages in Different Left Atrial Regions of Patients Undergoing Initial AF Ablation
Average voltage in sinus rhythm (mV)
Septum
Anterior
Floor
Lateral
Posterior
LA–PV Junction
Roof
Mitral Annulus
1.19 ± 0.90
1.24 ± 0.70
1.70 ± 1.25
1.43 ± 1.12
1.33 ± 1.12
1.02 ± 1.25
1.50 ± 1.00
1.12 ± 1.10
TABLE 3 95% Cutoff for Normal Bipolar Voltage in Different Left Atrial Regions of Patients Undergoing Initial AF Ablation
Bipolar voltage in sinus rhythm (mV)
Septum
Anterior
Floor
Lateral
Posterior
LA/PV Junction
Roof
Mitral Annulus
0.45
0.45
0.43
0.41
0.26
0.20
0.44
0.20
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TABLE 4 Average Bipolar Voltages by Region in Patients with Prior Left Atrial Ablation Presenting in Sinus Rhythm
Sinus rhythm average bipolar voltage (mV)
Septum
Anterior
Floor
Lateral/LAA
Posterior
LA/PV Junction
Roof
Mitral Annulus
0.98 ± 0.69
1.11 ± 0.72
1.06 ± 1.00
0.98 ± 0.87
0.51 ± 0.62
0.23 ± 0.32
1.08 ± 0.80
0.90 ± 0.82
Figure 4. Depicted are the relative differences in regional voltage distribution patients with and without prior left atrial ablations whose EAMs were acquired in sinus rhythm. Bipolar voltages were significantly reduced in the posterior LA and LA/PV junction in patients undergoing repeat AF ablation. For a high quality, full color version of this figure, please see Journal of Cardiovascular Electrophysiology’s website: www.wileyonlinelibrary.com/journal/jce
undergoing initial ablation showed scar on the CMRI. In the subjects undergoing repeat AF ablation, for points projecting in areas of LA scar on CMRI (n = 368), the mean bipolar voltage was 0.15 ± 0.15 mV. This was significantly lower than the mean bipolar voltage for control points (not projecting in areas of LA scar; n = 1,711 for subjects that had CMRI studies and were undergoing redo ablation), which was 0.96 ± 0.93 mV (P < 0.0001). It was also significantly lower than the mean bipolar voltage for patients without any LA scar on MRI (voltage = 1.34 ± 1.40 mV). Using ROC analysis of CMRI data (Fig. 7), the bipolar voltage cutoff that best separated points overlying LA scar as compared to control points was 0.27 mV (area under the curve–AUC: 0.92, sensitivity: 90%, specificity: 83%, positive predictive value: 40%, negative predictive value: 99%). This bipolar voltage cutoff value derived from CMRI data was quite similar to the bipolar voltage cutoff value of 0.2 mV that was independently determined from analysis of EAM data.
Discussion Our study provides EAM derived upper and lower bipolar voltage cutoff values that may be used to identify LA scar in patients undergoing repeat AF ablation. This to the best of our knowledge has never been previously shown.
Regional Bipolar Voltage Distribution in Left Atrium Heterogeneity in regional bipolar voltage distribution was seen in all patients in our series regardless of whether they had prior LA ablation, and the lowest values were seen in the posterior LA wall adjoining PVs. There are several explanations for this observation. Since the thickness of the myocardium is reflected in the signal amplitude, lower bipolar voltages may be recorded where the myocardial syncytium is thin. The LA posterior wall is one such area. Another possible explanation is that myocardium in locations adjoining structures with higher connective tissue content such as valves and PV ostia may manifest lower voltages. In a prior study, using a signal amplitude value recorded by 95% of all sampled points as being a cutoff for distinguishing healthy from unhealthy tissue, our group has shown that in truly normal patients (i.e., those without AF), the bipolar voltage cutoff value for healthy LA tissue is >0.50 mV.11 In the current study using an identical methodology we have identified 0.45 mV as the upper cutoff for identifying relatively healthy LA tissue in patients with AF. Although these values are close, the minor difference may be because of pre-existing fibrosis in the LA posterior wall of patients with AF compared to truly normal patients without AF.12-16 Consistent with this hypothesis, recent studies have shown DE abnormalities on CMRI along the LA posterior wall in patients with both paroxysmal and
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Figure 5. Illustrates bipolar voltage distribution in a patient who had undergone prior antral PVI. The voltage map was created in sinus rhythm using range of 0.20–0.45 mV. A: Demonstrates areas of dense scar (red) around the PVs—left veins are surrounded by scar and were chronically isolated. Preserved voltages (purple) were however seen along the septal and posterior aspects of the right veins (yellow arrows), which were sites of PV reconnection. Targeting these locations (B: red dots on septal aspect and pink dots on posterior aspect of right veins) alone was sufficient to achieve reisolation.
persistent AF.8,17 Also, a recent study that evaluated histopathology of ablation lesions in the RA of porcine hearts found that chronic radiofrequency ablation lesions typically manifested endocardial bipolar voltage amplitude of 0.3 mV.18 This closely approximates the cutoff values (0.2–0.45 mV) that we have established in the current study for identifying ablation related chronic scar in the LA of humans. However, it is possible that recognition of baseline LA fibrosis in AF patients that is unrelated to prior ablation lesions may require different bipolar voltage cut-off values than reported in our study.
terizing scar distribution may be a useful strategy to more effectively target PV reconnection. However, in this study we did not compare the efficacy of targeting PV reconnection using voltage guidance versus activation patterns of the circular mapping catheter positioned at the ostium of the reconnected veins. Also, even if PV entry block was achieved as per change of activation patterns on the circular mapping catheter during initial lesions in the PV segments demonstrating preserved voltages, additional lesions were still given to transect the entire segment (extending into the bordering scar as seen in Fig. 5B).
Correlating Bipolar Voltage Distribution and Recurrence of PV Conduction
Correlating EAM Bipolar Voltage Distribution with DE on CMRI
In our study voltage cutoff values of 0.2 to 0.45 mV on EAM acquired during sinus rhythm were reproducibly able to demonstrate scar around PVs in patients who had undergone prior AF ablation. These voltage settings were also able to reveal paucity of scar in segments around the PVs that had recovered conduction. Importantly, ablating at PV segments that demonstrated lack of scar resulted in isolation of the reconnected vein. Thus, our methodology for charac-
Using ROC analysis, a bipolar voltage cutoff value of 0.27 mV provided the best discrimination between healthy and unhealthy LA myocardium on CMRI. This value is very close to the lower cutoff value of 0.2 mV that we determined from EAM to identify scar in the LA–PV junction and LA posterior wall. However, for other LA locations on EAM, we found a voltage cutoff value of 0.45 mV more useful in discriminating relatively healthy from scarred LA myocardium.
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Figure 6. Illustrates bipolar voltage distribution in a patient who had undergone prior antral PVI (1 year earlier). The voltage map was created in sinus rhythm using range of 0.20–0.45 mV. A: Represents the LA shell in right anterior oblique projection and shows scar distribution along the septal aspect of right PVs; the area of reconnection was found near the septal carina and local voltage at this location (orange dot) measured 0.39 mV (red oval in adjoining panel; red arrow shows the local electrogram—EGM). In contrast, the voltage in the red scar region (blue dot) was 0.15 mV (yellow oval in adjoining panel; red arrow shows the local EGM). B: Shows the LA shell of the same patient in posterior projection; extensive red color is seen surrounding the left PVs (which remained chronically isolated) and the posterior aspect of right superior PV (local EGM measured 0.02 mV—yellow oval and arrow in adjoining panel); a small area of relatively preserved voltage is seen along the posterior aspect of right inferior PV that was the site of reconnection; local EGM (orange dot) at this location measured 0.32 mV (red oval and arrow in adjoining panel).
This discrepancy may be because the CMRI data used to correlate DE abnormalities with scar on EAM were exclusively from those patients who had undergone prior antral PVI. Thus, scar in these patients was expectedly in the posterior LA and around the PVs where a cutoff value of 0.2 mV is discriminatory. However, it is unclear from CMRI data if a higher cutoff value would be needed for identifying scar beyond the posterior LA. Based on the EAM data we propose using a scale with lower and upper cutoff values of 0.2 and 0.45 mV, respectively (instead of a single cutoff value at 0.2 mV), which allows better characterization of LA scar and takes into account regional heterogeneity in LA bipolar voltage distribution.
Clinical Implications Although PV entrance block (loss of vein potentials) documented by a multipolar circular mapping catheter positioned at the individual vein os, is the most common approach for validating PV isolation, correlating the activation patterns on the biploes of the circular mapping catheter with areas of reconnection along the PV antrum can be challenging. This is particularly true in the current era of wide area circumferential PV isolation during which the right and left pair of veins are often targeted en bloc. In these cases when the veins reconnect, identifying locations with preserved voltages along the antral lesion set may compliment the activation pattern of
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comment on how achieving isolation of reconnected veins by targeting areas of preserved voltages along PV antrum as described in this study compares to PV reisolation guided by electrogram recordings made with a circular mapping catheter placed at the PV ostium. Conclusion Contact electroanatomic mapping derived bipolar voltage cutoff value range of 0.2–0.45 mV, acquired during sinus rhythm may help localize sites of PV reconnection, in patients with AF undergoing repeat ablation for arrhythmia recurrences. References
Figure 7. Receiver–operator curves (ROC) analysis to determine optimal cutoff voltage values for discriminating left atrial scar from normal myocardium on CMRI. A bipolar cutoff of 0.27 appeared to offer the best sensitivity and specificity. AUC = area under the curve. For a high quality, full color version of this figure, please see Journal of Cardiovascular Electrophysiology’s website: www.wileyonlinelibrary.com/journal/jce
the circular mapping catheter for targeting more effectively the site of reconnection. Limitations Our study cohort is relatively small and comprised AF patients only. Even in the absence of prior ablation, these patients may have atrial fibrosis. Furthermore, our voltage cutoff for identifying atrial scarring was tested in patients who had undergone prior PV isolation. Thus, the voltage cutoffs established in our study may not be applicable for identifying healthy tissue in patients without AF and/or baseline fibrosis in AF patients who never had prior ablation. Since only patients who presented in SR were included in the study, we are unable to determine the effect of ongoing AF or flutter on LA voltage distribution. It also needs to be pointed out that although CMRI evidence of DE offers a surrogate assessment for LA scar, pathologic validation of the scar distribution vis-`a-vis EAM voltage cutoff criteria was not done for this study. Also, CMRI was not performed in all patients enrolled in the study. There can also be a registration error in the range of 3.0–3.5 mm when projecting EAM points on the CMRI image. In this study we exclusively used the CARTO system for EAM. Whether the voltage cutoff values for identifying LA scar derived using this system would apply to other EAM systems remains to be shown. Furthermore, we used a point-by-point technique to create the LA shell on the CARTO system. A mean of 141 ± 12 points were acquired per map with a fill threshold of 15. This approach of LA shell creation has been previously validated.19 However, we cannot comment on how our current approach for scar characterization compares to newer innovations which allow for denser point sampling using multipolar (Lasso or Pent-array) catheters. From histological sections of the LA–PV junction it has been shown that recovered PV conduction can occur over a small tissue area,13 which may not be adequately demonstrated by the mapping resolution achieved with a 3.5 mm tip catheter or for that matter, CMRI. We also cannot
1. Hutchinson MD, Gerstenfeld EP, Desjardins B, Bala R, Riley MP, Garcia FC, Dixit S, Lin D, Tzou WS, Cooper JM, Verdino RJ, Callans DJ, Marchlinski FE: Endocardial unipolar voltage mapping to detect epicardial ventricular tachycardia substrate in patients with nonischemic left ventricular cardiomyopathy. Circ Arrhythm Electrophysiol 2011;4:4955. 2. Hsia HH, Callans DJ, Marchlinski FE: Characterization of endocardial electrophysiological substrate in patients with nonischemic cardiomyopathy and monomorphic ventricular tachycardia. Circulation 2003;108:704-710. 3. Marra MP, Leoni L, Bauce B, Corbetti F, Zorzi A, Migliore F, Silvano M, Rigato I, Tona F, Tarantini G, Cacciavillani L, Basso C, Buja G, Thiene G, Iliceto S, Corrado D: Imaging study of ventricular scar in arrhythmogenic right ventricular cardiomyopathy: Comparison of 3D standard electroanatomical voltage mapping and contrast-enhanced cardiac magnetic resonance. Circ Arrhythm Electrophysiol 2012;5:91100. 4. Deneke T, Muller KM, Lemke B, Lawo T, Calcum B, Helwing M, Mugge A, Grewe PH: Human histopathology of electroanatomic mapping after cooled-tip radiofrequency ablation to treat ventricular tachycardia in remote myocardial infarction. J Cardiovasc Electrophysiol 2005;16:1246-1251. 5. Perin EC, Silva GV, Sarmento-Leite R, Sousa AL, Howell M, Muthupillai R, Lambert B, Vaughn WK, Flamm SD: Assessing myocardial viability and infarct transmurality with left ventricular electromechanical mapping in patients with stable coronary artery disease: Validation by delayed-enhancement magnetic resonance imaging. Circulation 2002;106:957-961. 6. Spragg DD, Khurram I, Zimmerman SL, Yarmohammadi H, Barcelon B, Needleman M, Edwards D, Marine JE, Calkins H, Nazarian S: Initial experience with magnetic resonance imaging of atrial scar and co-registration with electroanatomic voltage mapping during atrial fibrillation: Success and limitations. Heart Rhythm 2012;9:2003-2009. 7. Akoum N, Daccarett M, McGann C, Segerson N, Vergara G, Kuppahally S, Badger T, Burgon N, Haslam T, Kholmvoski E, Macleod R, Marrouche N: Atrial fibrosis helps select the appropriate patient and strategy in catheter ablation of atrial fibrillation: A DE-MRI guided approach. J Cardiovasc Electrophysiol 2011;22:16-22. 8. Oakes RS, Badger TJ, Kholmovski EG, Akoum N, Burgon NS, Fish EN, Blauer JJ, Rao SN, DiBella EV, Segerson NM, Daccarett M, Windfelder J, McGann CJ, Parker D, MacLeod RS, Marrouche NE: Detection and quantification of left atrial structural remodeling with delayed-enhancement magnetic resonance imaging in patients with atrial fibrillation. Circulation 2009;119:1758-1767. 9. Marchlinski FE, Callans D, Dixit S, Gerstenfeld EP, Rho R, Ren JF, Zado E: Efficacy and safety of targeted focal ablation versus PV isolation assisted by magnetic electroanatomic mapping. J Cardiovasc Electrophysiol 2003;14:358-365. 10. Pappone C, Rosanio S, Oreto G, Tocchi M, Gugliotta F, Vicedomini G, Salvati A, Dicandia C, Mazzone P, Santinelli V, Gulletta S, Chierchia S: Circumferential radiofrequency ablation of pulmonary vein ostia: A new anatomic approach for curing atrial fibrillation. Circulation 2000;102:2619-2628. 11. Saghy L, Callans DJ, Garcia F, Lin D, Marchlinski FE, Riley M, Dixit S, Tzou WS, Haqqani HM, Pap P, Kim S, Gerstenfeld EP: Is there a relationship between complex fractionated atrial electrograms recorded during atrial fibrillation and sinus rhythm fractionation? Heart Rhythm 2012;9:181-188.
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12. Bursten B, Nattel S: Atrial fibrosis: Mechanisms and clinical relevance in atrial fibrillation. J Am Coll Cardiol 2008;51:802-809. 13. Frustaci A, Chimenti C, Bellocci F, Morgante E, Russo MA, Maseri A: Histological substrate of atrial biopsies in patients with lone atrial fibrillation. Circulation 1997;96:1180-1184. 14. Everett TH, Olgin JE: Atrial fibrosis and the mechanisms of atrial fibrillation. Heart Rhythm 2007;4:S24-S27. 15. Yamazaki M, Jalife J: Pathophysiology of atrial fibrillation: From initiation to maintenance. J Arrhythmia 2012;28:129-139. 16. Zhao J, Butters TD, Zhang H, Pullan AJ, LeGrice IJ, Sands GB, Smaill BH. An image-based model of atrial muscular architecture: Effects of structural anisotropy on electrical activation. Circ Arrhythm Electrophysiol 2012;5:361-370. 17. Jadidi AS, Cochet H, Shah AJ, Kim SJ, Duncan E, Miyazaki S, Sermesant M, Lehrmann H, Lederlin M, Linton N, Forclaz A, Nault I, Rivard L, Wright M, Liu X, Scherr D, Wilton SB, Roten L, Pascale
P, Derval N, Sacher F, Knecht S, Keyl C, Hocini M, Montaudon M, Laurent F, Ha¨ıssaguerre M, Ja¨ıs P: Inverse relationship between fractionated electrograms and atrial fibrosis in persistent atrial fibrillation: Combined magnetic resonance imaging and high density mapping. J Am Coll Cardiol 2013;62:802-812. 18. Harrison JL, Jensen HK, Chiribiri A, Grøndal AK, Bloch LO, Pedersen SF, Bentzon JF, Kolbitsch C, Karim R, Williams SE, Linton NW, Rhode KS, Gill J, Cooklin M, Rinaldi CA, Wright M, Kim WY, Schaeffter T, Razavi RS, O’Neill MD: Cardiac magnetic resonance and electroanatomic mapping of acute and chronic ablation injury: A histologic validation study. Eur Heart J 2014 [Epub ahead of print]. 19. Dixit S, Marchlinski FE, Lin D, Callans DJ, Bala R, Riley MP, Garcia FC, Hutchinson MD, Ratcliffe SJ, Cooper JM, Verdino RJ, Patel VV, Zado ES, Cash NR, Killian T, Tomson TT, Gerstenfeld EP: Randomized ablation strategies for the treatment of persistent atrial fibrillation: RASTA study. Circ Arrhythm Electrophysiol 2011;5:287-294.
Contact Electroanatomic Mapping Derived Voltage Criteria for Characterizing Left Atrial Scar in Patients Undergoing Ablation for Atrial Fibrillation SURAJ KAPA, M.D.,∗ BENOIT DESJARDINS, M.D., Ph.D.,† DAVID J. CALLANS, M.D.,∗ FRANCIS E. MARCHLINSKI, M.D.,∗ and SANJAY DIXIT, M.D.∗ From the ∗ Division of Cardiac Electrophysiology, Department of Medicine; and †Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
Voltage Criteria for Left Atrial Scar. Background: Criteria have not been established for identifying LA scar using electroanatomic mapping (EAM). It is also unclear if voltage criteria using EAM may assist in identifying areas of pulmonary vein (PV) reconnection in patients undergoing repeat AF ablation. Objectives: To characterize left atrial (LA) voltage in patients undergoing atrial fibrillation (AF) ablation. Methods: An LA shell was created and bipolar voltage amplitude (in mV) at each point was measured. The shell was divided into 8 regions. Bipolar voltage values lower than the amplitude of 95% of sampled points was used as the upper cutoff value. Delayed enhancement (DE) cardiac magnetic resonance imaging (CMRI) sequences were performed to validate voltage cutoffs. Results: Twenty patients participated. A mean of 141 ± 12 points constituted the LA map that was created during sinus rhythm (SR). In patients undergoing initial AF ablation, mean bipolar LA voltage was 1.44 ± 1.27 mV. In patients undergoing repeat AF ablation, scar along the posterior wall and LA–PV junction was identified using a voltage cutoff 0.2 mV, whereas for other LA locations 95% of points demonstrated signal amplitude >0.45 mV.
TABLE 1
Characteristic
Voltage Criteria for Left Atrial Scar
58 ± 6 8 (80%) 8 (80%) 2 (20%) 2 (20%) 1 (10%) 1 (10%) 2 (20%) 57 ± 12 4.4 ± 0.9 4 (40%) 6 (60%) 5 (50%) 5 (50%) 3 (30%)
63 ± 10 6 (60%) 6 (60%) 1 (10%) 0 (0%) 0 (0%) 2 (20%) 0 (0%) 61 ± 9 4.0 ± 0.5 6 (60%) 4 (40%) 10 (100%) 3 (30%) 3 (30%)
61 ± 9 14 (70%) 14 (70%) 3 (15%) 2 (10%) 5 (5%) 3 (15%) 2 (10%) 59 ± 11 4.2 ± 0.7 10 (50%) 10 (50%) 15 (75%) 8 (40%) 6 (30%)
6 (60%)
5 (50%)
11 (55%)
Results Patient Population A total of 20 patients comprised the study cohort (paroxysmal AF in 12 [60%]). Patient characteristics are detailed in Table 1. Ten subjects were undergoing their first ablation procedure and 10 subjects were undergoing repeat AF ablation. In subjects undergoing repeat ablation, the initial procedure was antral PVI alone in 8 (80%), and in 2 patients, additional MA, and LA roof lines were performed. Voltage Characterization in Patients Undergoing Initial AF Ablation A mean of 141 ± 12 points per patient constituted the LA map in this group. Approximately 63% of these points (89 ± 10) were located in the PV antrum including the posterior LA, adjoining septum, roof, and anterior ridge. The overall bipolar voltage of the LA in this group of patients was 1.44 ± 1.27 mV. The LA floor manifested the highest mean voltages (1.70 ± 1.25 mV), whereas LA–PV junction had the lowest mean voltages (1.02 ± 1.25 mV; Table 2). Table 3 summarizes the bipolar voltage cutoff value, which was below the amplitude of 95% of the points sampled in each anatomic segment. Specifically for the posterior wall and LA–PV junc-
Voltage Characterization in Patients with Prior Left Atrial Ablation Table 4 summarizes the regional voltage distribution in this group of patients. Since all patients in this group had undergone prior antral PVI, as expected, the lowest mean bipolar voltages were found in the posterior wall (0.51 ± 0.62 mV) and LA–PV junction (0.23 ± 0.32 mV) and these were significantly reduced as compared with other LA regions (P < 0.01 for both the LA–PV and posterior wall compared with other regions). Among all the LA regions, only the LA–PV junction and posterior wall showed lower mean amplitude in patients undergoing repeat AF ablation as compared to patients undergoing initial AF ablation (P < 0.01 for LA–PV junction and posterior wall, NS for other regions, Fig. 4). In the patients undergoing repeat AF ablation (n = 10), using voltage settings of 0.2–0.45 mV (established from analysis of bipolar voltage information in patients with sinus rhythm undergoing initial AF ablation), scar was clearly identified around the PVs (Fig. 5A). Furthermore, in PVs showing evidence of electrical reconnection, we were also able to demonstrate segmental areas of relatively preserved voltage around the LA–PV junction. A total of 17 segments at the LA–PV junction of reconnected veins demonstrated preserved voltages and their distribution was as follows: septal aspect of the right PVs in 6 patients, posterior roof bordering right PVs in 6 patients, anterior ridge of the left PVs in 2 patients and the posterior aspect of left PVs in 3 patients. The mean signal amplitude of these segments with preserved voltages was 0.9 ± 0.2 mV (range 0.32–1.3 mV) and none of the points in these reconnected segments demonstrated a voltage < 0.3 mV (Fig. 6). During reisolation of these veins, a mean of 9 ± 5 lesions were required to traverse these segments with preserved voltages (Fig. 5B). Of note, in all chronically isolated PVs, DE abnormality in a circumferential distribution was seen on the MRI study at the time of repeat ablation. DE-MRI-Voltage Mapping Correlation Preprocedure CMRI studies were performed in 12 of the 20 study patients (60%; 6 undergoing initial ablation and 6 undergoing repeat ablation). None of the subjects
TABLE 2 Average Voltages in Different Left Atrial Regions of Patients Undergoing Initial AF Ablation
Average voltage in sinus rhythm (mV)
Septum
Anterior
Floor
Lateral
Posterior
LA–PV Junction
Roof
Mitral Annulus
1.19 ± 0.90
1.24 ± 0.70
1.70 ± 1.25
1.43 ± 1.12
1.33 ± 1.12
1.02 ± 1.25
1.50 ± 1.00
1.12 ± 1.10
TABLE 3 95% Cutoff for Normal Bipolar Voltage in Different Left Atrial Regions of Patients Undergoing Initial AF Ablation
Bipolar voltage in sinus rhythm (mV)
Septum
Anterior
Floor
Lateral
Posterior
LA/PV Junction
Roof
Mitral Annulus
0.45
0.45
0.43
0.41
0.26
0.20
0.44
0.20
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TABLE 4 Average Bipolar Voltages by Region in Patients with Prior Left Atrial Ablation Presenting in Sinus Rhythm
Sinus rhythm average bipolar voltage (mV)
Septum
Anterior
Floor
Lateral/LAA
Posterior
LA/PV Junction
Roof
Mitral Annulus
0.98 ± 0.69
1.11 ± 0.72
1.06 ± 1.00
0.98 ± 0.87
0.51 ± 0.62
0.23 ± 0.32
1.08 ± 0.80
0.90 ± 0.82
Figure 4. Depicted are the relative differences in regional voltage distribution patients with and without prior left atrial ablations whose EAMs were acquired in sinus rhythm. Bipolar voltages were significantly reduced in the posterior LA and LA/PV junction in patients undergoing repeat AF ablation. For a high quality, full color version of this figure, please see Journal of Cardiovascular Electrophysiology’s website: www.wileyonlinelibrary.com/journal/jce
undergoing initial ablation showed scar on the CMRI. In the subjects undergoing repeat AF ablation, for points projecting in areas of LA scar on CMRI (n = 368), the mean bipolar voltage was 0.15 ± 0.15 mV. This was significantly lower than the mean bipolar voltage for control points (not projecting in areas of LA scar; n = 1,711 for subjects that had CMRI studies and were undergoing redo ablation), which was 0.96 ± 0.93 mV (P < 0.0001). It was also significantly lower than the mean bipolar voltage for patients without any LA scar on MRI (voltage = 1.34 ± 1.40 mV). Using ROC analysis of CMRI data (Fig. 7), the bipolar voltage cutoff that best separated points overlying LA scar as compared to control points was 0.27 mV (area under the curve–AUC: 0.92, sensitivity: 90%, specificity: 83%, positive predictive value: 40%, negative predictive value: 99%). This bipolar voltage cutoff value derived from CMRI data was quite similar to the bipolar voltage cutoff value of 0.2 mV that was independently determined from analysis of EAM data.
Discussion Our study provides EAM derived upper and lower bipolar voltage cutoff values that may be used to identify LA scar in patients undergoing repeat AF ablation. This to the best of our knowledge has never been previously shown.
Regional Bipolar Voltage Distribution in Left Atrium Heterogeneity in regional bipolar voltage distribution was seen in all patients in our series regardless of whether they had prior LA ablation, and the lowest values were seen in the posterior LA wall adjoining PVs. There are several explanations for this observation. Since the thickness of the myocardium is reflected in the signal amplitude, lower bipolar voltages may be recorded where the myocardial syncytium is thin. The LA posterior wall is one such area. Another possible explanation is that myocardium in locations adjoining structures with higher connective tissue content such as valves and PV ostia may manifest lower voltages. In a prior study, using a signal amplitude value recorded by 95% of all sampled points as being a cutoff for distinguishing healthy from unhealthy tissue, our group has shown that in truly normal patients (i.e., those without AF), the bipolar voltage cutoff value for healthy LA tissue is >0.50 mV.11 In the current study using an identical methodology we have identified 0.45 mV as the upper cutoff for identifying relatively healthy LA tissue in patients with AF. Although these values are close, the minor difference may be because of pre-existing fibrosis in the LA posterior wall of patients with AF compared to truly normal patients without AF.12-16 Consistent with this hypothesis, recent studies have shown DE abnormalities on CMRI along the LA posterior wall in patients with both paroxysmal and
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Figure 5. Illustrates bipolar voltage distribution in a patient who had undergone prior antral PVI. The voltage map was created in sinus rhythm using range of 0.20–0.45 mV. A: Demonstrates areas of dense scar (red) around the PVs—left veins are surrounded by scar and were chronically isolated. Preserved voltages (purple) were however seen along the septal and posterior aspects of the right veins (yellow arrows), which were sites of PV reconnection. Targeting these locations (B: red dots on septal aspect and pink dots on posterior aspect of right veins) alone was sufficient to achieve reisolation.
persistent AF.8,17 Also, a recent study that evaluated histopathology of ablation lesions in the RA of porcine hearts found that chronic radiofrequency ablation lesions typically manifested endocardial bipolar voltage amplitude of 0.3 mV.18 This closely approximates the cutoff values (0.2–0.45 mV) that we have established in the current study for identifying ablation related chronic scar in the LA of humans. However, it is possible that recognition of baseline LA fibrosis in AF patients that is unrelated to prior ablation lesions may require different bipolar voltage cut-off values than reported in our study.
terizing scar distribution may be a useful strategy to more effectively target PV reconnection. However, in this study we did not compare the efficacy of targeting PV reconnection using voltage guidance versus activation patterns of the circular mapping catheter positioned at the ostium of the reconnected veins. Also, even if PV entry block was achieved as per change of activation patterns on the circular mapping catheter during initial lesions in the PV segments demonstrating preserved voltages, additional lesions were still given to transect the entire segment (extending into the bordering scar as seen in Fig. 5B).
Correlating Bipolar Voltage Distribution and Recurrence of PV Conduction
Correlating EAM Bipolar Voltage Distribution with DE on CMRI
In our study voltage cutoff values of 0.2 to 0.45 mV on EAM acquired during sinus rhythm were reproducibly able to demonstrate scar around PVs in patients who had undergone prior AF ablation. These voltage settings were also able to reveal paucity of scar in segments around the PVs that had recovered conduction. Importantly, ablating at PV segments that demonstrated lack of scar resulted in isolation of the reconnected vein. Thus, our methodology for charac-
Using ROC analysis, a bipolar voltage cutoff value of 0.27 mV provided the best discrimination between healthy and unhealthy LA myocardium on CMRI. This value is very close to the lower cutoff value of 0.2 mV that we determined from EAM to identify scar in the LA–PV junction and LA posterior wall. However, for other LA locations on EAM, we found a voltage cutoff value of 0.45 mV more useful in discriminating relatively healthy from scarred LA myocardium.
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Figure 6. Illustrates bipolar voltage distribution in a patient who had undergone prior antral PVI (1 year earlier). The voltage map was created in sinus rhythm using range of 0.20–0.45 mV. A: Represents the LA shell in right anterior oblique projection and shows scar distribution along the septal aspect of right PVs; the area of reconnection was found near the septal carina and local voltage at this location (orange dot) measured 0.39 mV (red oval in adjoining panel; red arrow shows the local electrogram—EGM). In contrast, the voltage in the red scar region (blue dot) was 0.15 mV (yellow oval in adjoining panel; red arrow shows the local EGM). B: Shows the LA shell of the same patient in posterior projection; extensive red color is seen surrounding the left PVs (which remained chronically isolated) and the posterior aspect of right superior PV (local EGM measured 0.02 mV—yellow oval and arrow in adjoining panel); a small area of relatively preserved voltage is seen along the posterior aspect of right inferior PV that was the site of reconnection; local EGM (orange dot) at this location measured 0.32 mV (red oval and arrow in adjoining panel).
This discrepancy may be because the CMRI data used to correlate DE abnormalities with scar on EAM were exclusively from those patients who had undergone prior antral PVI. Thus, scar in these patients was expectedly in the posterior LA and around the PVs where a cutoff value of 0.2 mV is discriminatory. However, it is unclear from CMRI data if a higher cutoff value would be needed for identifying scar beyond the posterior LA. Based on the EAM data we propose using a scale with lower and upper cutoff values of 0.2 and 0.45 mV, respectively (instead of a single cutoff value at 0.2 mV), which allows better characterization of LA scar and takes into account regional heterogeneity in LA bipolar voltage distribution.
Clinical Implications Although PV entrance block (loss of vein potentials) documented by a multipolar circular mapping catheter positioned at the individual vein os, is the most common approach for validating PV isolation, correlating the activation patterns on the biploes of the circular mapping catheter with areas of reconnection along the PV antrum can be challenging. This is particularly true in the current era of wide area circumferential PV isolation during which the right and left pair of veins are often targeted en bloc. In these cases when the veins reconnect, identifying locations with preserved voltages along the antral lesion set may compliment the activation pattern of
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comment on how achieving isolation of reconnected veins by targeting areas of preserved voltages along PV antrum as described in this study compares to PV reisolation guided by electrogram recordings made with a circular mapping catheter placed at the PV ostium. Conclusion Contact electroanatomic mapping derived bipolar voltage cutoff value range of 0.2–0.45 mV, acquired during sinus rhythm may help localize sites of PV reconnection, in patients with AF undergoing repeat ablation for arrhythmia recurrences. References
Figure 7. Receiver–operator curves (ROC) analysis to determine optimal cutoff voltage values for discriminating left atrial scar from normal myocardium on CMRI. A bipolar cutoff of 0.27 appeared to offer the best sensitivity and specificity. AUC = area under the curve. For a high quality, full color version of this figure, please see Journal of Cardiovascular Electrophysiology’s website: www.wileyonlinelibrary.com/journal/jce
the circular mapping catheter for targeting more effectively the site of reconnection. Limitations Our study cohort is relatively small and comprised AF patients only. Even in the absence of prior ablation, these patients may have atrial fibrosis. Furthermore, our voltage cutoff for identifying atrial scarring was tested in patients who had undergone prior PV isolation. Thus, the voltage cutoffs established in our study may not be applicable for identifying healthy tissue in patients without AF and/or baseline fibrosis in AF patients who never had prior ablation. Since only patients who presented in SR were included in the study, we are unable to determine the effect of ongoing AF or flutter on LA voltage distribution. It also needs to be pointed out that although CMRI evidence of DE offers a surrogate assessment for LA scar, pathologic validation of the scar distribution vis-`a-vis EAM voltage cutoff criteria was not done for this study. Also, CMRI was not performed in all patients enrolled in the study. There can also be a registration error in the range of 3.0–3.5 mm when projecting EAM points on the CMRI image. In this study we exclusively used the CARTO system for EAM. Whether the voltage cutoff values for identifying LA scar derived using this system would apply to other EAM systems remains to be shown. Furthermore, we used a point-by-point technique to create the LA shell on the CARTO system. A mean of 141 ± 12 points were acquired per map with a fill threshold of 15. This approach of LA shell creation has been previously validated.19 However, we cannot comment on how our current approach for scar characterization compares to newer innovations which allow for denser point sampling using multipolar (Lasso or Pent-array) catheters. From histological sections of the LA–PV junction it has been shown that recovered PV conduction can occur over a small tissue area,13 which may not be adequately demonstrated by the mapping resolution achieved with a 3.5 mm tip catheter or for that matter, CMRI. We also cannot
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