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Left atrial low-voltage areas predict atrial fibrillation recurrence after catheter ablation in patients with paroxysmal atrial fibrillation
International Journal of Cardiology 257 (2018) 97–101
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International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Left atrial low-voltage areas predict atrial fibrillation recurrence after catheter ablation in patients with paroxysmal atrial fibrillation Masaharu Masuda ⁎,1, Masashi Fujita 1, Osamu Iida 1, Shin Okamoto 1, Takayuki Ishihara 1, Kiyonori Nanto 1, Takashi Kanda 1, Takuya Tsujimura 1, Yasuhiro Matsuda 1, Shota Okuno 1, Takuya Ohashi 1, Aki Tsuji 1, Toshiaki Mano 1 Kansai Rosai Hospital Cardiovascular Center, 3-1-69 Inabaso, Amagasaki, Hyogo 660-0060, Japan
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Article history: Received 11 November 2017 Accepted 21 December 2017 Keywords: Low-voltage area Paroxysmal atrial fibrillation Recurrence
a b s t r a c t Background: Association between the presence of left atrial low-voltage areas and atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) has been shown mainly in persistent AF patients. We sought to compare the AF recurrence rate in paroxysmal AF patients with and without left atrial low-voltage areas. Methods: This prospective observational study included 147 consecutive patients undergoing initial ablation for paroxysmal AF. Voltage mapping was performed after PVI during sinus rhythm, and low-voltage areas were defined as regions where bipolar peak-to-peak voltage was b 0.50 mV. Results: Left atrial low-voltage areas after PVI were observed in 22 (15%) patients. Patients with low-voltage areas were significantly older (72 ± 6 vs. 66 ± 10, p b 0.0001), more likely to be female (68% vs. 32%, p = 0.002), and had higher CHA2DS2-VASc score (2.5 ± 1.5 vs. 1.8 ± 1.3, p = 0.028). During a mean follow-up of 22 (18, 26) months, AF recurrence was observed in 24 (16%) and 16 (11%) patients after the single and multiple ablation procedures, respectively. AF recurrence rate after multiple ablations was higher in patients with low-voltage areas than without (36% vs. 6%, p b 0.001). Low-voltage areas were independently associated with AF recurrence even after adjustment for the other related factors (Hazard ratio, 5.89; 95% confidence interval, 2.16 to 16.0, p = 0.001). Conclusion: The presence of left atrial low-voltage areas after PVI predicts AF recurrence in patients with paroxysmal AF as well as in patients with persistent AF. © 2017 Elsevier B.V. All rights reserved.
1. Introduction Left atrial bipolar voltage during sinus rhythm (SR) decreases in parallel with the progression of atrial fibrillation (AF) [1]. Recently, the presence of left atrial low-voltage areas after pulmonary vein isolation (PVI) has been shown to be a powerful predictor of AF recurrence, and patients with low-voltage area ablation following PVI demonstrated better long-term outcomes than historical controls receiving PVI alone [2–7]. Because a majority of these study patients had persistent AF, low-voltage ablation has become an important option for the treatment of persistent AF. Some paroxysmal AF patients also have these low-voltage areas. However, the impact of low-voltage areas on rhythm outcomes after PVI in paroxysmal AF patients has not sufficiently been studied.
⁎ Corresponding author at: Kansai Rosai Hospital Cardiovascular Center, 3-1-69 Inabaso, Amagasaki-shi, Hyogo 660-8511, Japan. E-mail address: [email protected] (M. Masuda). 1 These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
https://doi.org/10.1016/j.ijcard.2017.12.089 0167-5273/© 2017 Elsevier B.V. All rights reserved.
Here, we sought to compare the AF recurrence rates in paroxysmal AF patients with and without left atrial low-voltage areas. 2. Methods 2.1. Patients This prospective observational study enrolled 147 consecutive patients who underwent initial ablation of paroxysmal AF at Kansai Rosai Hospital from December 2014 to March 2016. Paroxysmal AF was defined as episodes of AF that terminated spontaneously in b7 days. Exclusion criteria were age b20 years, prior cardiac surgery, and prior catheter ablation. This study complied with the Declaration of Helsinki. Written informed consent for the ablation and participation in the study was obtained from all patients, and the protocol was approved by our institutional review board. 2.2. Radiofrequency catheter ablation procedure Electrophysiological studies and catheter ablation were performed by two experienced operators (MM and TK) with the patient under intravenous sedation with dexmedetomidine. A 6-Fr decapolar electrode was inserted into the coronary sinus while a second 6-Fr decapolar electrode was placed in the right atrium. Following a transseptal puncture at the fossa ovalis, two long sheaths were introduced into the left atrium. A 20-pole circular catheter was placed in a pulmonary vein via the sheath. During sinus rhythm, isoproterenol was infused at 5, 10, and 20 μg/min at 2-minute intervals and discontinued to provoke ectopies and AF. Subsequently, the operators performed mapping
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M. Masuda et al. / International Journal of Cardiology 257 (2018) 97–101
and ablation guided by an electroanatomical mapping system (Carto3®; Biosense Webster, Diamond Bar CA, USA). A dragging technique was employed to perform circumferential ablation around both ipsilateral pulmonary veins using an open-irrigated ablation catheter with a 3.5-mm tip (Thermocool SmartTouch®; Biosense Webster) via an Agilis® or SL0® sheath (St. Jude Medical, St. Paul MN, USA). Radiofrequency energy was applied for 30 s (15 s at the posterior left atrial wall near the esophagus) at each site using a maximum temperature of 42 °C and maximum power of 35 W. The irrigation rate was 17 ml/min. Operators attempted to maintain an appropriate contact force between the catheter and endocardium of between 5 and 20 g. PVI was considered complete when both entrance and exit blocks were created. If atrial flutter was observed spontaneously or induced by atrial burst stimuli, additional ablation was performed. After a N20-min waiting period following the last ablation lesion, 20 mg of adenosine was rapidly administered intravenously to provoke possible dormant conduction. Further ablation was performed until every dormant conduction provoked by repeat adenosine injection was eliminated. 2.3. Voltage mapping
PVI was achieved in all patients. The rates of other ablations for clinical and induced ectopies or tachyarrhythmias were equal between the two groups. No severe complication associated with the ablation procedures developed. 3.2. Voltage mapping After the PVI, a voltage map was created during sinus rhythm in all patients. The number of mapping points was 142 (101, 170). LVAs existed in 22 (15%) patients with an area of 16 ± 13 cm2, occupying 17% ± 13% of the left atrial surface area. LVAs were predominantly observed in the septal (14 [10%] patients), anterior (11 [7%]), roof (9 [6%]), and posterior (9 [6%]) regions, and rarely observed in the inferior (3 [2%]) and posterolateral (1 [1%]) regions.
Following the PVI, detailed voltage mapping using a bipolar 3.5-mm tip catheter (Thermocool SmartTouch®) was performed during sinus rhythm in accordance with a previous study (Fig. S1) [2]. Mapping points were acquired evenly throughout the entire left atrium to fill all color gaps on the voltage map using the electroanatomical mapping system with an interpolation threshold of 15 mm for the fill threshold and 23 mm for the color threshold. In addition, high-density mapping was performed at sites where low-voltage areas had been detected to delineate exactly the extent of each low-voltage area. We confirmed adequate endocardial contact by stable electrograms, the distance to the geometry surface, and contact force ≥5 g. The band pass filter was set at 30 to 500 Hz. Bipolar peak-to-peak voltage at each acquired point was measured. We defined low-voltage areas as sites of ≥3 adjacent low-voltage (b 0.5 mV) points which were b5 mm apart.
3.3. AF recurrence after the initial ablation
2.4. Follow-up
3.4. Repeated ablation procedures
Patients were followed up every 4–8 weeks at the dedicated arrhythmia clinic of our institution for a minimum of 1 year. Routine ECGs were obtained at each outpatient visit, and 24-h ambulatory Holter monitoring was performed 6 and 12 months post-ablation. When patients experienced symptoms suggestive of an arrhythmia, a surface ECG, ambulatory ECG, and/or cardiac event recording were also obtained. Either of the following events after the initial 3 months from the ablation (blanking period) was considered to indicate atrial tachyarrhythmia (AF and regular atrial tachycardia) recurrence: [1] atrial tachyarrhythmia recorded on a routine or symptom-triggered ECG during an outpatient visit, or [2] atrial tachyarrhythmia of at least a 30 s duration on ambulatory ECG monitoring. No antiarrhythmic drugs were prescribed after the ablation procedure unless recurrent atrial tachyarrhythmia was observed. Patients with recurrent atrial tachyarrhythmia were recommended to undergo a repeat ablation procedure including re-isolation of reconnected PVs, ablation of AF triggers from any non-PV foci, and ablation for induced atrial tachycardia. 2.5. Statistical analysis Continuous data are expressed as the mean ± standard deviation or median (interquartile range). Categorical data are presented as absolute values and percentages. Tests for significance were conducted using the unpaired t-test, or nonparametric test (Mann–Whiney U test) for continuous variables, and the chi-squared test or Fisher's exact test for categorical variables. Univariate and multivariate Cox proportional hazard models were used to determine the clinical factors that were associated with atrial-tachyarrhythmia recurrence. Variables with a p value ≤0.10 in the univariate models were included in the multivariate analysis. Atrial tachyarrhythmia-free survival rates were calculated using the Kaplan–Meier method. Comparison of survival curves between the groups was performed with a 2-sided Mantel–Haenszel (log-rank) test. All analyses were performed using commercial software (SPSS version 22.0®, SPSS, Inc., Chicago IL, USA).
3. Results 3.1. Patient characteristics Left atrial low-voltage areas after PV isolation were observed in 22 (15%) patients. Comparisons of baseline and procedural characteristics are shown in Table 1. Patients with low-voltage areas were significantly older, more likely to be female, had higher CHA2DS2-VASc score, higher DR-FLASH score [8], and higher early transmitral flow velocity/early mitral annular velocity (E/e′) than those without. In addition, there were tendencies toward higher brain natriuretic peptide levels and lower creatinine clearance in patients with low-voltage areas than in those without.
During a mean follow-up period of 22 (18, 26) months, AF recurrence developed in 24 (16%) patients after the initial ablation. AF recurrence rate after the initial ablation procedure was higher in patients with low-voltage areas than in those without (9 [41%] vs. 15[12%], p = 0.001). On the other hand, patients with low-voltage areas demonstrated a significantly higher AF recurrence rate after multiple procedures than those without (8 [36%] vs. 8 [6%], p b 0.0001). The Kaplan–Meier curves of AF recurrence-free rates are shown in Fig. 1.
Among the 24 patients with AF recurrence after the initial ablation, 16 (67%) patients underwent repeated ablations. The other eight patients did not receive a repeated ablation due to (1) retreat from Table 1 Baseline and procedural characteristics. Low-voltage area
Age, years Female, n (%) Body mass index, kg/m2 Atrial fibrillation duration, months Hypertension, n (%) Diabetes mellitus, n (%) Heart failure, n (%) Coronary artery disease, n (%) CHA2DS2-VASc score Brain natriuretic peptide, pg/ml Creatinine clearance, ml/min Echocardiography findings Left atrial diameter, mm Left ventricular ejection fraction, % E/A E/e′ Mitral regurgitation, n (%) Maintenance dialysis, n (%) DR-FLASH scorea Antiarrhythmic drug usage, n (%) Ablation procedure Pulmonary vein isolation, n (%) Cavo-tricuspid isthmus ablation, n (%) Other ablationsb, n (%) Radiofrequency time, s
p
With
Without
n = 22
n = 125
72 ± 6 15 (68) 23.1 ± 4.8 6 (3, 12) 12 (55) 3 (14) 2 (9) 2 (9) 2.5 ± 1.5 79 (38, 227) 67 ± 21
66 ± 10 40 (32) 23.5 ± 3.5 6 (4, 20) 67 (54) 14 (11) 5 (14) 5 (4) 1.8 ± 1.3 38 (18, 73) 79 ± 29
b0.0001 0.002 0.61 0.53 1.0 0.72 0.28 0.28 0.028 0.057 0.059
38 ± 7 61 ± 10 1.15 ± 0.59 13.3 ± 5.1 5 (23) 2 (9) 2.6 ± 0.9 15 (68)
36 ± 6 60 ± 11 1.02 ± 0.40 10.1 ± 3.3 18 (14) 3 (2) 1.8 ± 1.1 63 (50)
0.34 0.77 0.25 0.019 0.34 0.16 0.001 0.17
22 (100) 2 (9) 1 (5) 1574 ± 471
125 (100) 12 (10) 3 (2) 1560 ± 570
0.99 0.99 0.94
E and A indicates diastolic early and late transmitral flow velocities; e′, diastolic early mitral annular velocity. a DR-FLASH is a score to estimate the presence of low-voltage area by assigning 1 point for each quality: diabetes mellitus, renal dysfunction, persistent form of atrial fibrillation, left atrial diameter N45 mm, age N65 years, female sex, and hypertension. b Other ablation procedures included a superior vena cava isolation for atrial fibrillation trigger ectopy (2 patients) and a mitral isthmus linear ablation for an induced perimitral flutter (2 patients).
M. Masuda et al. / International Journal of Cardiology 257 (2018) 97–101
ablating refractory AF due to extremely broad low-voltage areas and/or multiple AF trigger ectopies originating from non-PV foci at the initial ablation in six patients, and (2) patient refusal to undergo repeated ablation in two patients. Electrophysiological findings and ablation details in repeated ablations are shown in Table 2. A majority of the patients without low-voltage areas were free from AF recurrence after re-isolation of reconnected PVs. However, those with low-voltage areas still suffered from residual AF even after extensive atrial ablation in addition to PVI (linear lesions, non-PV ectopies) (Fig. 1). Clinical factors associated with AF recurrence after multiple ablations are displayed in Table 3. The existence of low-voltage areas was independently associated with AF recurrence even after adjustment for left atrial size. 4. Discussion This prospective observational study included 147 consecutive paroxysmal AF patients undergoing AF ablation. Left atrial low-voltage areas existed in 22 (15%) patients. After multiple repeated ablations, patients with low-voltage areas developed recurrent AF at approximately six times the rate as those without low-voltage areas even after adjustment for the other related factors. To our knowledge, this is the largest clinical study describing the prognostic impact of low-voltage areas in paroxysmal AF patients. 4.1. Low-voltage areas in patients with paroxysmal AF Previous studies including both paroxysmal and persistent AF consistently demonstrated that low-voltage areas exist more frequently in
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patients with persistent AF [2,7–9]. There seems to be a positive association between low-voltage areas and persistent AF. Low-voltage areas most likely act as arrhythmogenic substrates, promoting more persistent AF by slowing electrical conduction and sustaining fibrillatory conduction [10]. On the other hand, the AF episode results in electrical and structural remodeling in the atria [11]. Thus, the persistent form of AF more strongly impairs atrial myocardial viability and decreases atrial voltage. Low-voltage areas were also observed in patients with paroxysmal AF, with a prevalence of 15% in this study and 10% to 34% in prior studies [2,7–9]. The pathophysiologic mechanism underlying atrial voltage decrease in paroxysmal AF is likely different from that in persistent AF in which atrial remodeling is, partially at least, caused by the AF persistence itself. The results of this study (Table 1) and other reports suggests that the generation of low-voltage areas in paroxysmal AF would likely be more dependent on other factors causing atrial remodeling, such as aging, female gender [7,8,12]. In addition, an elevated left atrial pressure, which was represented by a high E/e′ (Table 1), would also contribute to left atrial remodeling as recently reported. 4.2. Prognostic impact of low-voltage areas in paroxysmal AF This study demonstrated the association of left atrial low-voltage areas with AF recurrence following ablation. The effect was more significant after multiple ablation procedures than after the initial procedure, probably because other factors associated with AF recurrence, such as an electrical reconnection between pulmonary vein and atrium, were likely to be eliminated after multiple procedures. Notably, the rhythm outcome after PVI for paroxysmal AF in patients without low-voltage areas was excellent, with a long-term AF-free rate of N 90%. In contrast, the outcome in paroxysmal AF patients with lowvoltage areas was unsatisfactory (AF-free rate of approximately 60%). Several studies including mainly persistent AF patients have suggested that patients undergoing ablation targeting low-voltage areas had rhythm outcomes non-inferior to those without low-voltage areas [2,9]. In addition, Kottkamp et al. demonstrated the efficacy of lowvoltage-area elimination on a rhythm outcome in paroxysmal AF patients undergoing repeat AF ablation procedures. An ongoing randomized controlled trial comparing the AF recurrence rates between patients with and without a low-voltage-area ablation in paroxysmal AF patients (http://www.umin.ac.jp/ctr/index.htm, UMIN000023403) will provide some important insights into this issue. 4.3. Comparison with a prior study Recently, Vlachos et al. reported the association between the existence of low-voltage areas and AF recurrence in a relatively small
Table 2 Electrophysiological findings and ablation details in repeated ablations. Low-voltage areas
Number of repeated ablation procedure ≥2, n (%) Type of recurrent atrial tachyarrhythmias Atrial fibrillation, n (%) Regular atrial tachycardia, n (%) Pulmonary vein-left atrium reconnection, n (%) Ablation lesions in addition to PV isolation Cavo-tricuspid isthmus, n (%) Left atrial linear, n (%) Trigger from non-pulmonary-vein-focia, n (%) Recurrence after the last ablation, n (%) Fig. 1. Kaplan–Meier curves of AF recurrence-free rates. Kaplan–Meier curves of AF recurrence-free rates after the initial (A) and the last ablations (B) are shown. Patients with low-voltage areas had significantly higher recurrence rates after the initial and last ablations.
p
With
Without
n=6
n = 10
3 (50)
0 (0)
0.030
6 (100) 2 (33) 3 (50)
9 (90) 1 (10) 8 (80)
1.00 0.30 0.30
3 (50) 3 (50) 2 (33) 5 (83)
3 (30) 1 (10) 3 (30) 3 (30)
0.61 0.12 0.99 0.12
a The origins of the triggers from non-pulmonary-vein-foci were 1 superior vena cava and 1 left atrial septal region in patients with low-voltage areas, and 1 superior vena cava, 1 left atrial posterior region, and 1 right atrial septal region.
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Table 3 Factors associated with atrial fibrillation recurrencea after the last ablation. Recurrence
Age, years Female, n (%) Body mass index AF periods, months Hypertension, n (%) Diabetes mellitus, n (%) Heart failure, n (%) Coronary artery disease, n (%) CHA2DS2-VASc score Brain natriuretic peptide, pg/ml Left atrial diameter, mm E/e′ Maintenance dialysis, n (%) Low-voltage area, n (%)
Univariate
Multivariate
With n = 16
Without n = 131
HR
95% CI
p
70 ± 8 8 (50) 23.4 ± 4.4 6 (3, 12) 7 (44) 2 (13) 1 (6) 1 (6) 2.1 ± 1.4 58 (35, 326) 39 ± 6 12.2 ± 6.6 2 (13) 8 (50)
67 ± 10 47 (36) 23.5 ± 3.7 6 (4, 20) 72 (55) 15 (12) 6 (5) 13 (10) 1.9 ± 1.3 39 (18, 81) 36 ± 3 10.4 ± 3.4 3 (2) 14 (11)
1.03 1.68 0.99 0.99 0.63 1.06 1.25 0.63 1.13 1.001 1.07 1.10 5.26 6.64
0.97–1.10 0.63–4.49 0.87–1.13 0.96–1.02 0.23–1.68 0.24–4.67 0.16–9.43 0.08–4.76 0.80–1.61 1.000–1.002 0.99–1.17 0.97–1.26 1.19–23.3 2.49–17.7
0.28 0.30 0.89 0.48 0.35 0.94 0.83 0.65 0.49 0.095 0.090 0.13 0.029 0.001
HR
95% CI
p
1.000 1.04
0.998–1.002 0.96–1.13
0.94 0.32
3.46 5.89
0.47–25.8 2.16–16.0
0.23 0.001
Factors with p b 0.10 in the univariate analysis were incorporated in the multivariate analysis. HR, hazard ratio; CI, confidence interval. Abbreviations as in Table 1. a Atrial fibrillation recurrence indicates the recurrence of both atrial fibrillation and atrial tachycardia.
number of patients (n = 80) [14]. They used a criterion of the lowvoltage areas described as b0.4 mV and N 10% of the total left atrial surface. AF recurrence rate during a follow-up period of 17.8 ± 3.8 months was higher in patients with low-voltage areas (37%) than in those without (16%, p = 0.027). Notably, the study patient had a relatively diseased left atrial myocardium, which was represented by a very high incidence of left atrial low-voltage areas (54%). The advantages of the present study were as follows. Our study included a larger number of patients with a less diseased atrial myocardium (incidence of low-voltage areas, 15%), which was more consistent with those in the previous studies (10%–34%) than that in the study by Vlachos et al. [2,7–9]. Furthermore, our study presented the AF recurrence after multiple ablation procedures, which would ensure the PVI durability and emphasize the impact of low-voltage areas on the rhythm outcome.
4.4. Limitations Several limitations of this study warrant mention. First, as we conducted voltage mapping after completion of PVI, low-voltage areas near the pulmonary vein antrum could not be determined precisely due to ablation scar. Second, extremely small low-voltage areas might have been missed due to the limited resolution of the voltage maps. However, a previous report has suggested that small, isolated lowvoltage areas have less influence on arrhythmogenicity than large low-voltage areas [15]. Third, ablation procedures adjunctive to PVI in the repeat sessions were dependent on electrophysiological findings, which were not necessarily consistent. This might bias the AF recurrence rate after multiple ablations. Fourth, AF recurrences after discharge were quantitated on the basis of the patients' symptoms, giving rise to the possibility that asymptomatic episodes of AF might have been missed. Fifth, the existence of low-voltage areas was assessed during the initial ablation session. However, some low-voltage areas might be reversible and the distribution of low-voltage areas could differ during the follow-up period. Finally, the small number of AF recurrences due to the small sample size limits the statistical accuracy.
5. Conclusion The presence of left atrial low-voltage areas after PVI predicts recurrence in patients with paroxysmal AF. Supplementary data to this article can be found online at https://doi. org/10.1016/j.ijcard.2017.12.089.
Author contributions Concept, design, drafting the manuscript: M. Masuda. Data collection and revising the manuscript: M. Fujita, O. Iida, S. Okamoto, T. Ishihara, K. Nanto, T. Kanda, A. Tsujimura, Y. Matsuda, T. Ohashi, A. Tsuji. Final approval of the manuscript: T. Mano. Financial support None. Conflict of interest None. References [1] Y. Lin, B. Yang, F.C. Garcia, W. Ju, F. Zhang, H. Chen, J. Yu, M. Li, K. Gu, K. Cao, D.J. Callans, F.E. Marchlinski, M. Chen, Comparison of left atrial electrophysiologic abnormalities during sinus rhythm in patients with different type of atrial fibrillation, J. Interv. Card. Electrophysiol. 39 (2014) 57–67. [2] S. Rolf, S. Kircher, A. Arya, C. Eitel, P. Sommer, S. Richter, T. Gaspar, A. Bollmann, D. Altmann, C. Piedra, G. Hindricks, C. Piorkowski, Tailored atrial substrate modification based on low-voltage areas in catheter ablation of atrial fibrillation, Circ. Arrhythm. Electrophysiol. 7 (2014) 825–833. [3] G. Yang, B. Yang, Y. Wei, F. Zhang, W. Ju, H. Chen, M. Li, K. Gu, Y. Lin, B. Wang, K. Cao, P. Kojodjojo, M. Chen, Catheter ablation of nonparoxysmal atrial fibrillation using electrophysiologically guided substrate modification during sinus rhythm after pulmonary vein isolation, Circ. Arrhythm. Electrophysiol. 9 (2016), e003382. https://doi.org/10.1161/CIRCEP.115.003382. [4] H. Kottkamp, J. Berg, R. Bender, A. Rieger, D. Schreiber, Box isolation of fibrotic areas (BIFA): a patient-tailored substrate modification approach for ablation of atrial fibrillation, J. Cardiovasc. Electrophysiol. 27 (2016) 22–30. [5] A.S. Jadidi, H. Lehrmann, C. Keyl, J. Sorrel, V. Markstein, J. Minners, C.I. Park, A. Denis, P. Jaïs, M. Hocini, C. Potocnik, J. Allgeier, W. Hochholzer, C. Herrera-Sidloky, S. Kim, Y.E. Omri, F.J. Neumann, R. Weber, M. Haïssaguerre, T. Arentz, Ablation of persistent atrial fibrillation targeting low-voltage areas with selective activation characteristics, Circ. Arrhythm. Electrophysiol. 9 (2016)https://doi.org/10.1161/CIRCEP.115. 002962. [6] T. Yamaguchi, T. Tsuchiya, S. Nakahara, A. Fukui, Y. Nagamoto, K. Murotani, K. Eshima, N. Takahashi, Efficacy of left atrial voltage-based catheter ablation of persistent atrial fibrillation, J. Cardiovasc. Electrophysiol. 27 (2016) 1055–1063. [7] M. Masuda, M. Fujita, O. Iida, S. Okamoto, T. Ishihara, K. Nanto, T. Kanda, T. Shiraki, A. Sunaga, Y. Matsuda, M. Uematsu, Influence of underlying substrate on atrial tachyarrhythmias after pulmonary vein isolation, Heart Rhythm. 13 (2016) 870–878. [8] J. Kosiuk, B. Dinov, J. Kornej, W.J. Acou, R. Schönbauer, L. Fiedler, P. Buchta, K. Myrda, M. Gąsior, L. Poloński, S. Kircher, A. Arya, P. Sommer, A. Bollmann, G. Hindricks, S. Rolf, Prospective, multicenter validation of a clinical risk score for left atrial arrhythmogenic substrate based on voltage analysis: DR-FLASH score, Heart Rhythm. 12 (2015) 2207–2212. [9] A. Yagishita, J.R. Gimbel, S. DE Oliveira, H. Manyam, D. Sparano, I. Cakulev, J. Mackall, M. Arruda, Long-term outcome of left atrial voltage-guided substrate ablation
M. Masuda et al. / International Journal of Cardiology 257 (2018) 97–101 during atrial fibrillation: a novel adjunctive ablation strategy, J. Cardiovasc. Electrophysiol. 28 (2017) 147–155. [10] K. Miyamoto, T. Tsuchiya, S. Narita, T. Yamaguchi, Y. Nagamoto, S. Ando, K. Hayashida, Y. Tanioka, N. Takahashi, Bipolar electrogram amplitudes in the left atrium are related to local conduction velocity in patients with atrial fibrillation, Europace 11 (2009) 1597–1605. [11] M.C. Wijffels, C.J. Kirchhof, R. Dorland, M.A. Allessie, Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats, Circulation 92 (1995) 1954–1968. [12] J. Park, B. Joung, J.S. Uhm, C. Young Shim, C. Hwang, M. Hyoung Lee, H.N. Pak, High left atrial pressures are associated with advanced electroanatomical remodeling of
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left atrium and independent predictors for clinical recurrence of atrial fibrillation after catheter ablation, Heart Rhythm. 11 (2014) 953–960. [14] K. Vlachos, M. Efremidis, K.P. Letsas, G. Bazoukis, R. Martin, M. Kalafateli, et al., Lowvoltage areas detected by high-density electroanatomical mapping predict recurrence after ablation for paroxysmal atrial fibrillation, J. Cardiovasc. Electrophysiol. (2017) https://doi.org/10.1111/jce.13321. [15] A. Verma, O.M. Wazni, N.F. Marrouche, D.O. Martin, F. Kilicaslan, S. Minor, R.A. Schweikert, W. Saliba, J. Cummings, J.D. Burkhardt, M. Bhargava, W.A. Belden, A. Abdul-Karim, A. Natale, Pre-existent left atrial scarring in patients undergoing pulmonary vein antrum isolation: an independent predictor of procedural failure, J. Am. Coll. Cardiol. 45 (2005) 285–292.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Left atrial low-voltage areas predict atrial fibrillation recurrence after catheter ablation in patients with paroxysmal atrial fibrillation Masaharu Masuda ⁎,1, Masashi Fujita 1, Osamu Iida 1, Shin Okamoto 1, Takayuki Ishihara 1, Kiyonori Nanto 1, Takashi Kanda 1, Takuya Tsujimura 1, Yasuhiro Matsuda 1, Shota Okuno 1, Takuya Ohashi 1, Aki Tsuji 1, Toshiaki Mano 1 Kansai Rosai Hospital Cardiovascular Center, 3-1-69 Inabaso, Amagasaki, Hyogo 660-0060, Japan
a r t i c l e
i n f o
Article history: Received 11 November 2017 Accepted 21 December 2017 Keywords: Low-voltage area Paroxysmal atrial fibrillation Recurrence
a b s t r a c t Background: Association between the presence of left atrial low-voltage areas and atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) has been shown mainly in persistent AF patients. We sought to compare the AF recurrence rate in paroxysmal AF patients with and without left atrial low-voltage areas. Methods: This prospective observational study included 147 consecutive patients undergoing initial ablation for paroxysmal AF. Voltage mapping was performed after PVI during sinus rhythm, and low-voltage areas were defined as regions where bipolar peak-to-peak voltage was b 0.50 mV. Results: Left atrial low-voltage areas after PVI were observed in 22 (15%) patients. Patients with low-voltage areas were significantly older (72 ± 6 vs. 66 ± 10, p b 0.0001), more likely to be female (68% vs. 32%, p = 0.002), and had higher CHA2DS2-VASc score (2.5 ± 1.5 vs. 1.8 ± 1.3, p = 0.028). During a mean follow-up of 22 (18, 26) months, AF recurrence was observed in 24 (16%) and 16 (11%) patients after the single and multiple ablation procedures, respectively. AF recurrence rate after multiple ablations was higher in patients with low-voltage areas than without (36% vs. 6%, p b 0.001). Low-voltage areas were independently associated with AF recurrence even after adjustment for the other related factors (Hazard ratio, 5.89; 95% confidence interval, 2.16 to 16.0, p = 0.001). Conclusion: The presence of left atrial low-voltage areas after PVI predicts AF recurrence in patients with paroxysmal AF as well as in patients with persistent AF. © 2017 Elsevier B.V. All rights reserved.
1. Introduction Left atrial bipolar voltage during sinus rhythm (SR) decreases in parallel with the progression of atrial fibrillation (AF) [1]. Recently, the presence of left atrial low-voltage areas after pulmonary vein isolation (PVI) has been shown to be a powerful predictor of AF recurrence, and patients with low-voltage area ablation following PVI demonstrated better long-term outcomes than historical controls receiving PVI alone [2–7]. Because a majority of these study patients had persistent AF, low-voltage ablation has become an important option for the treatment of persistent AF. Some paroxysmal AF patients also have these low-voltage areas. However, the impact of low-voltage areas on rhythm outcomes after PVI in paroxysmal AF patients has not sufficiently been studied.
⁎ Corresponding author at: Kansai Rosai Hospital Cardiovascular Center, 3-1-69 Inabaso, Amagasaki-shi, Hyogo 660-8511, Japan. E-mail address: [email protected] (M. Masuda). 1 These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
https://doi.org/10.1016/j.ijcard.2017.12.089 0167-5273/© 2017 Elsevier B.V. All rights reserved.
Here, we sought to compare the AF recurrence rates in paroxysmal AF patients with and without left atrial low-voltage areas. 2. Methods 2.1. Patients This prospective observational study enrolled 147 consecutive patients who underwent initial ablation of paroxysmal AF at Kansai Rosai Hospital from December 2014 to March 2016. Paroxysmal AF was defined as episodes of AF that terminated spontaneously in b7 days. Exclusion criteria were age b20 years, prior cardiac surgery, and prior catheter ablation. This study complied with the Declaration of Helsinki. Written informed consent for the ablation and participation in the study was obtained from all patients, and the protocol was approved by our institutional review board. 2.2. Radiofrequency catheter ablation procedure Electrophysiological studies and catheter ablation were performed by two experienced operators (MM and TK) with the patient under intravenous sedation with dexmedetomidine. A 6-Fr decapolar electrode was inserted into the coronary sinus while a second 6-Fr decapolar electrode was placed in the right atrium. Following a transseptal puncture at the fossa ovalis, two long sheaths were introduced into the left atrium. A 20-pole circular catheter was placed in a pulmonary vein via the sheath. During sinus rhythm, isoproterenol was infused at 5, 10, and 20 μg/min at 2-minute intervals and discontinued to provoke ectopies and AF. Subsequently, the operators performed mapping
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and ablation guided by an electroanatomical mapping system (Carto3®; Biosense Webster, Diamond Bar CA, USA). A dragging technique was employed to perform circumferential ablation around both ipsilateral pulmonary veins using an open-irrigated ablation catheter with a 3.5-mm tip (Thermocool SmartTouch®; Biosense Webster) via an Agilis® or SL0® sheath (St. Jude Medical, St. Paul MN, USA). Radiofrequency energy was applied for 30 s (15 s at the posterior left atrial wall near the esophagus) at each site using a maximum temperature of 42 °C and maximum power of 35 W. The irrigation rate was 17 ml/min. Operators attempted to maintain an appropriate contact force between the catheter and endocardium of between 5 and 20 g. PVI was considered complete when both entrance and exit blocks were created. If atrial flutter was observed spontaneously or induced by atrial burst stimuli, additional ablation was performed. After a N20-min waiting period following the last ablation lesion, 20 mg of adenosine was rapidly administered intravenously to provoke possible dormant conduction. Further ablation was performed until every dormant conduction provoked by repeat adenosine injection was eliminated. 2.3. Voltage mapping
PVI was achieved in all patients. The rates of other ablations for clinical and induced ectopies or tachyarrhythmias were equal between the two groups. No severe complication associated with the ablation procedures developed. 3.2. Voltage mapping After the PVI, a voltage map was created during sinus rhythm in all patients. The number of mapping points was 142 (101, 170). LVAs existed in 22 (15%) patients with an area of 16 ± 13 cm2, occupying 17% ± 13% of the left atrial surface area. LVAs were predominantly observed in the septal (14 [10%] patients), anterior (11 [7%]), roof (9 [6%]), and posterior (9 [6%]) regions, and rarely observed in the inferior (3 [2%]) and posterolateral (1 [1%]) regions.
Following the PVI, detailed voltage mapping using a bipolar 3.5-mm tip catheter (Thermocool SmartTouch®) was performed during sinus rhythm in accordance with a previous study (Fig. S1) [2]. Mapping points were acquired evenly throughout the entire left atrium to fill all color gaps on the voltage map using the electroanatomical mapping system with an interpolation threshold of 15 mm for the fill threshold and 23 mm for the color threshold. In addition, high-density mapping was performed at sites where low-voltage areas had been detected to delineate exactly the extent of each low-voltage area. We confirmed adequate endocardial contact by stable electrograms, the distance to the geometry surface, and contact force ≥5 g. The band pass filter was set at 30 to 500 Hz. Bipolar peak-to-peak voltage at each acquired point was measured. We defined low-voltage areas as sites of ≥3 adjacent low-voltage (b 0.5 mV) points which were b5 mm apart.
3.3. AF recurrence after the initial ablation
2.4. Follow-up
3.4. Repeated ablation procedures
Patients were followed up every 4–8 weeks at the dedicated arrhythmia clinic of our institution for a minimum of 1 year. Routine ECGs were obtained at each outpatient visit, and 24-h ambulatory Holter monitoring was performed 6 and 12 months post-ablation. When patients experienced symptoms suggestive of an arrhythmia, a surface ECG, ambulatory ECG, and/or cardiac event recording were also obtained. Either of the following events after the initial 3 months from the ablation (blanking period) was considered to indicate atrial tachyarrhythmia (AF and regular atrial tachycardia) recurrence: [1] atrial tachyarrhythmia recorded on a routine or symptom-triggered ECG during an outpatient visit, or [2] atrial tachyarrhythmia of at least a 30 s duration on ambulatory ECG monitoring. No antiarrhythmic drugs were prescribed after the ablation procedure unless recurrent atrial tachyarrhythmia was observed. Patients with recurrent atrial tachyarrhythmia were recommended to undergo a repeat ablation procedure including re-isolation of reconnected PVs, ablation of AF triggers from any non-PV foci, and ablation for induced atrial tachycardia. 2.5. Statistical analysis Continuous data are expressed as the mean ± standard deviation or median (interquartile range). Categorical data are presented as absolute values and percentages. Tests for significance were conducted using the unpaired t-test, or nonparametric test (Mann–Whiney U test) for continuous variables, and the chi-squared test or Fisher's exact test for categorical variables. Univariate and multivariate Cox proportional hazard models were used to determine the clinical factors that were associated with atrial-tachyarrhythmia recurrence. Variables with a p value ≤0.10 in the univariate models were included in the multivariate analysis. Atrial tachyarrhythmia-free survival rates were calculated using the Kaplan–Meier method. Comparison of survival curves between the groups was performed with a 2-sided Mantel–Haenszel (log-rank) test. All analyses were performed using commercial software (SPSS version 22.0®, SPSS, Inc., Chicago IL, USA).
3. Results 3.1. Patient characteristics Left atrial low-voltage areas after PV isolation were observed in 22 (15%) patients. Comparisons of baseline and procedural characteristics are shown in Table 1. Patients with low-voltage areas were significantly older, more likely to be female, had higher CHA2DS2-VASc score, higher DR-FLASH score [8], and higher early transmitral flow velocity/early mitral annular velocity (E/e′) than those without. In addition, there were tendencies toward higher brain natriuretic peptide levels and lower creatinine clearance in patients with low-voltage areas than in those without.
During a mean follow-up period of 22 (18, 26) months, AF recurrence developed in 24 (16%) patients after the initial ablation. AF recurrence rate after the initial ablation procedure was higher in patients with low-voltage areas than in those without (9 [41%] vs. 15[12%], p = 0.001). On the other hand, patients with low-voltage areas demonstrated a significantly higher AF recurrence rate after multiple procedures than those without (8 [36%] vs. 8 [6%], p b 0.0001). The Kaplan–Meier curves of AF recurrence-free rates are shown in Fig. 1.
Among the 24 patients with AF recurrence after the initial ablation, 16 (67%) patients underwent repeated ablations. The other eight patients did not receive a repeated ablation due to (1) retreat from Table 1 Baseline and procedural characteristics. Low-voltage area
Age, years Female, n (%) Body mass index, kg/m2 Atrial fibrillation duration, months Hypertension, n (%) Diabetes mellitus, n (%) Heart failure, n (%) Coronary artery disease, n (%) CHA2DS2-VASc score Brain natriuretic peptide, pg/ml Creatinine clearance, ml/min Echocardiography findings Left atrial diameter, mm Left ventricular ejection fraction, % E/A E/e′ Mitral regurgitation, n (%) Maintenance dialysis, n (%) DR-FLASH scorea Antiarrhythmic drug usage, n (%) Ablation procedure Pulmonary vein isolation, n (%) Cavo-tricuspid isthmus ablation, n (%) Other ablationsb, n (%) Radiofrequency time, s
p
With
Without
n = 22
n = 125
72 ± 6 15 (68) 23.1 ± 4.8 6 (3, 12) 12 (55) 3 (14) 2 (9) 2 (9) 2.5 ± 1.5 79 (38, 227) 67 ± 21
66 ± 10 40 (32) 23.5 ± 3.5 6 (4, 20) 67 (54) 14 (11) 5 (14) 5 (4) 1.8 ± 1.3 38 (18, 73) 79 ± 29
b0.0001 0.002 0.61 0.53 1.0 0.72 0.28 0.28 0.028 0.057 0.059
38 ± 7 61 ± 10 1.15 ± 0.59 13.3 ± 5.1 5 (23) 2 (9) 2.6 ± 0.9 15 (68)
36 ± 6 60 ± 11 1.02 ± 0.40 10.1 ± 3.3 18 (14) 3 (2) 1.8 ± 1.1 63 (50)
0.34 0.77 0.25 0.019 0.34 0.16 0.001 0.17
22 (100) 2 (9) 1 (5) 1574 ± 471
125 (100) 12 (10) 3 (2) 1560 ± 570
0.99 0.99 0.94
E and A indicates diastolic early and late transmitral flow velocities; e′, diastolic early mitral annular velocity. a DR-FLASH is a score to estimate the presence of low-voltage area by assigning 1 point for each quality: diabetes mellitus, renal dysfunction, persistent form of atrial fibrillation, left atrial diameter N45 mm, age N65 years, female sex, and hypertension. b Other ablation procedures included a superior vena cava isolation for atrial fibrillation trigger ectopy (2 patients) and a mitral isthmus linear ablation for an induced perimitral flutter (2 patients).
M. Masuda et al. / International Journal of Cardiology 257 (2018) 97–101
ablating refractory AF due to extremely broad low-voltage areas and/or multiple AF trigger ectopies originating from non-PV foci at the initial ablation in six patients, and (2) patient refusal to undergo repeated ablation in two patients. Electrophysiological findings and ablation details in repeated ablations are shown in Table 2. A majority of the patients without low-voltage areas were free from AF recurrence after re-isolation of reconnected PVs. However, those with low-voltage areas still suffered from residual AF even after extensive atrial ablation in addition to PVI (linear lesions, non-PV ectopies) (Fig. 1). Clinical factors associated with AF recurrence after multiple ablations are displayed in Table 3. The existence of low-voltage areas was independently associated with AF recurrence even after adjustment for left atrial size. 4. Discussion This prospective observational study included 147 consecutive paroxysmal AF patients undergoing AF ablation. Left atrial low-voltage areas existed in 22 (15%) patients. After multiple repeated ablations, patients with low-voltage areas developed recurrent AF at approximately six times the rate as those without low-voltage areas even after adjustment for the other related factors. To our knowledge, this is the largest clinical study describing the prognostic impact of low-voltage areas in paroxysmal AF patients. 4.1. Low-voltage areas in patients with paroxysmal AF Previous studies including both paroxysmal and persistent AF consistently demonstrated that low-voltage areas exist more frequently in
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patients with persistent AF [2,7–9]. There seems to be a positive association between low-voltage areas and persistent AF. Low-voltage areas most likely act as arrhythmogenic substrates, promoting more persistent AF by slowing electrical conduction and sustaining fibrillatory conduction [10]. On the other hand, the AF episode results in electrical and structural remodeling in the atria [11]. Thus, the persistent form of AF more strongly impairs atrial myocardial viability and decreases atrial voltage. Low-voltage areas were also observed in patients with paroxysmal AF, with a prevalence of 15% in this study and 10% to 34% in prior studies [2,7–9]. The pathophysiologic mechanism underlying atrial voltage decrease in paroxysmal AF is likely different from that in persistent AF in which atrial remodeling is, partially at least, caused by the AF persistence itself. The results of this study (Table 1) and other reports suggests that the generation of low-voltage areas in paroxysmal AF would likely be more dependent on other factors causing atrial remodeling, such as aging, female gender [7,8,12]. In addition, an elevated left atrial pressure, which was represented by a high E/e′ (Table 1), would also contribute to left atrial remodeling as recently reported. 4.2. Prognostic impact of low-voltage areas in paroxysmal AF This study demonstrated the association of left atrial low-voltage areas with AF recurrence following ablation. The effect was more significant after multiple ablation procedures than after the initial procedure, probably because other factors associated with AF recurrence, such as an electrical reconnection between pulmonary vein and atrium, were likely to be eliminated after multiple procedures. Notably, the rhythm outcome after PVI for paroxysmal AF in patients without low-voltage areas was excellent, with a long-term AF-free rate of N 90%. In contrast, the outcome in paroxysmal AF patients with lowvoltage areas was unsatisfactory (AF-free rate of approximately 60%). Several studies including mainly persistent AF patients have suggested that patients undergoing ablation targeting low-voltage areas had rhythm outcomes non-inferior to those without low-voltage areas [2,9]. In addition, Kottkamp et al. demonstrated the efficacy of lowvoltage-area elimination on a rhythm outcome in paroxysmal AF patients undergoing repeat AF ablation procedures. An ongoing randomized controlled trial comparing the AF recurrence rates between patients with and without a low-voltage-area ablation in paroxysmal AF patients (http://www.umin.ac.jp/ctr/index.htm, UMIN000023403) will provide some important insights into this issue. 4.3. Comparison with a prior study Recently, Vlachos et al. reported the association between the existence of low-voltage areas and AF recurrence in a relatively small
Table 2 Electrophysiological findings and ablation details in repeated ablations. Low-voltage areas
Number of repeated ablation procedure ≥2, n (%) Type of recurrent atrial tachyarrhythmias Atrial fibrillation, n (%) Regular atrial tachycardia, n (%) Pulmonary vein-left atrium reconnection, n (%) Ablation lesions in addition to PV isolation Cavo-tricuspid isthmus, n (%) Left atrial linear, n (%) Trigger from non-pulmonary-vein-focia, n (%) Recurrence after the last ablation, n (%) Fig. 1. Kaplan–Meier curves of AF recurrence-free rates. Kaplan–Meier curves of AF recurrence-free rates after the initial (A) and the last ablations (B) are shown. Patients with low-voltage areas had significantly higher recurrence rates after the initial and last ablations.
p
With
Without
n=6
n = 10
3 (50)
0 (0)
0.030
6 (100) 2 (33) 3 (50)
9 (90) 1 (10) 8 (80)
1.00 0.30 0.30
3 (50) 3 (50) 2 (33) 5 (83)
3 (30) 1 (10) 3 (30) 3 (30)
0.61 0.12 0.99 0.12
a The origins of the triggers from non-pulmonary-vein-foci were 1 superior vena cava and 1 left atrial septal region in patients with low-voltage areas, and 1 superior vena cava, 1 left atrial posterior region, and 1 right atrial septal region.
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Table 3 Factors associated with atrial fibrillation recurrencea after the last ablation. Recurrence
Age, years Female, n (%) Body mass index AF periods, months Hypertension, n (%) Diabetes mellitus, n (%) Heart failure, n (%) Coronary artery disease, n (%) CHA2DS2-VASc score Brain natriuretic peptide, pg/ml Left atrial diameter, mm E/e′ Maintenance dialysis, n (%) Low-voltage area, n (%)
Univariate
Multivariate
With n = 16
Without n = 131
HR
95% CI
p
70 ± 8 8 (50) 23.4 ± 4.4 6 (3, 12) 7 (44) 2 (13) 1 (6) 1 (6) 2.1 ± 1.4 58 (35, 326) 39 ± 6 12.2 ± 6.6 2 (13) 8 (50)
67 ± 10 47 (36) 23.5 ± 3.7 6 (4, 20) 72 (55) 15 (12) 6 (5) 13 (10) 1.9 ± 1.3 39 (18, 81) 36 ± 3 10.4 ± 3.4 3 (2) 14 (11)
1.03 1.68 0.99 0.99 0.63 1.06 1.25 0.63 1.13 1.001 1.07 1.10 5.26 6.64
0.97–1.10 0.63–4.49 0.87–1.13 0.96–1.02 0.23–1.68 0.24–4.67 0.16–9.43 0.08–4.76 0.80–1.61 1.000–1.002 0.99–1.17 0.97–1.26 1.19–23.3 2.49–17.7
0.28 0.30 0.89 0.48 0.35 0.94 0.83 0.65 0.49 0.095 0.090 0.13 0.029 0.001
HR
95% CI
p
1.000 1.04
0.998–1.002 0.96–1.13
0.94 0.32
3.46 5.89
0.47–25.8 2.16–16.0
0.23 0.001
Factors with p b 0.10 in the univariate analysis were incorporated in the multivariate analysis. HR, hazard ratio; CI, confidence interval. Abbreviations as in Table 1. a Atrial fibrillation recurrence indicates the recurrence of both atrial fibrillation and atrial tachycardia.
number of patients (n = 80) [14]. They used a criterion of the lowvoltage areas described as b0.4 mV and N 10% of the total left atrial surface. AF recurrence rate during a follow-up period of 17.8 ± 3.8 months was higher in patients with low-voltage areas (37%) than in those without (16%, p = 0.027). Notably, the study patient had a relatively diseased left atrial myocardium, which was represented by a very high incidence of left atrial low-voltage areas (54%). The advantages of the present study were as follows. Our study included a larger number of patients with a less diseased atrial myocardium (incidence of low-voltage areas, 15%), which was more consistent with those in the previous studies (10%–34%) than that in the study by Vlachos et al. [2,7–9]. Furthermore, our study presented the AF recurrence after multiple ablation procedures, which would ensure the PVI durability and emphasize the impact of low-voltage areas on the rhythm outcome.
4.4. Limitations Several limitations of this study warrant mention. First, as we conducted voltage mapping after completion of PVI, low-voltage areas near the pulmonary vein antrum could not be determined precisely due to ablation scar. Second, extremely small low-voltage areas might have been missed due to the limited resolution of the voltage maps. However, a previous report has suggested that small, isolated lowvoltage areas have less influence on arrhythmogenicity than large low-voltage areas [15]. Third, ablation procedures adjunctive to PVI in the repeat sessions were dependent on electrophysiological findings, which were not necessarily consistent. This might bias the AF recurrence rate after multiple ablations. Fourth, AF recurrences after discharge were quantitated on the basis of the patients' symptoms, giving rise to the possibility that asymptomatic episodes of AF might have been missed. Fifth, the existence of low-voltage areas was assessed during the initial ablation session. However, some low-voltage areas might be reversible and the distribution of low-voltage areas could differ during the follow-up period. Finally, the small number of AF recurrences due to the small sample size limits the statistical accuracy.
5. Conclusion The presence of left atrial low-voltage areas after PVI predicts recurrence in patients with paroxysmal AF. Supplementary data to this article can be found online at https://doi. org/10.1016/j.ijcard.2017.12.089.
Author contributions Concept, design, drafting the manuscript: M. Masuda. Data collection and revising the manuscript: M. Fujita, O. Iida, S. Okamoto, T. Ishihara, K. Nanto, T. Kanda, A. Tsujimura, Y. Matsuda, T. Ohashi, A. Tsuji. Final approval of the manuscript: T. Mano. Financial support None. Conflict of interest None. References [1] Y. Lin, B. Yang, F.C. Garcia, W. Ju, F. Zhang, H. Chen, J. Yu, M. Li, K. Gu, K. Cao, D.J. Callans, F.E. Marchlinski, M. Chen, Comparison of left atrial electrophysiologic abnormalities during sinus rhythm in patients with different type of atrial fibrillation, J. Interv. Card. Electrophysiol. 39 (2014) 57–67. [2] S. Rolf, S. Kircher, A. Arya, C. Eitel, P. Sommer, S. Richter, T. Gaspar, A. Bollmann, D. Altmann, C. Piedra, G. Hindricks, C. Piorkowski, Tailored atrial substrate modification based on low-voltage areas in catheter ablation of atrial fibrillation, Circ. Arrhythm. Electrophysiol. 7 (2014) 825–833. [3] G. Yang, B. Yang, Y. Wei, F. Zhang, W. Ju, H. Chen, M. Li, K. Gu, Y. Lin, B. Wang, K. Cao, P. Kojodjojo, M. Chen, Catheter ablation of nonparoxysmal atrial fibrillation using electrophysiologically guided substrate modification during sinus rhythm after pulmonary vein isolation, Circ. Arrhythm. Electrophysiol. 9 (2016), e003382. https://doi.org/10.1161/CIRCEP.115.003382. [4] H. Kottkamp, J. Berg, R. Bender, A. Rieger, D. Schreiber, Box isolation of fibrotic areas (BIFA): a patient-tailored substrate modification approach for ablation of atrial fibrillation, J. Cardiovasc. Electrophysiol. 27 (2016) 22–30. [5] A.S. Jadidi, H. Lehrmann, C. Keyl, J. Sorrel, V. Markstein, J. Minners, C.I. Park, A. Denis, P. Jaïs, M. Hocini, C. Potocnik, J. Allgeier, W. Hochholzer, C. Herrera-Sidloky, S. Kim, Y.E. Omri, F.J. Neumann, R. Weber, M. Haïssaguerre, T. Arentz, Ablation of persistent atrial fibrillation targeting low-voltage areas with selective activation characteristics, Circ. Arrhythm. Electrophysiol. 9 (2016)https://doi.org/10.1161/CIRCEP.115. 002962. [6] T. Yamaguchi, T. Tsuchiya, S. Nakahara, A. Fukui, Y. Nagamoto, K. Murotani, K. Eshima, N. Takahashi, Efficacy of left atrial voltage-based catheter ablation of persistent atrial fibrillation, J. Cardiovasc. Electrophysiol. 27 (2016) 1055–1063. [7] M. Masuda, M. Fujita, O. Iida, S. Okamoto, T. Ishihara, K. Nanto, T. Kanda, T. Shiraki, A. Sunaga, Y. Matsuda, M. Uematsu, Influence of underlying substrate on atrial tachyarrhythmias after pulmonary vein isolation, Heart Rhythm. 13 (2016) 870–878. [8] J. Kosiuk, B. Dinov, J. Kornej, W.J. Acou, R. Schönbauer, L. Fiedler, P. Buchta, K. Myrda, M. Gąsior, L. Poloński, S. Kircher, A. Arya, P. Sommer, A. Bollmann, G. Hindricks, S. Rolf, Prospective, multicenter validation of a clinical risk score for left atrial arrhythmogenic substrate based on voltage analysis: DR-FLASH score, Heart Rhythm. 12 (2015) 2207–2212. [9] A. Yagishita, J.R. Gimbel, S. DE Oliveira, H. Manyam, D. Sparano, I. Cakulev, J. Mackall, M. Arruda, Long-term outcome of left atrial voltage-guided substrate ablation
M. Masuda et al. / International Journal of Cardiology 257 (2018) 97–101 during atrial fibrillation: a novel adjunctive ablation strategy, J. Cardiovasc. Electrophysiol. 28 (2017) 147–155. [10] K. Miyamoto, T. Tsuchiya, S. Narita, T. Yamaguchi, Y. Nagamoto, S. Ando, K. Hayashida, Y. Tanioka, N. Takahashi, Bipolar electrogram amplitudes in the left atrium are related to local conduction velocity in patients with atrial fibrillation, Europace 11 (2009) 1597–1605. [11] M.C. Wijffels, C.J. Kirchhof, R. Dorland, M.A. Allessie, Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats, Circulation 92 (1995) 1954–1968. [12] J. Park, B. Joung, J.S. Uhm, C. Young Shim, C. Hwang, M. Hyoung Lee, H.N. Pak, High left atrial pressures are associated with advanced electroanatomical remodeling of
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left atrium and independent predictors for clinical recurrence of atrial fibrillation after catheter ablation, Heart Rhythm. 11 (2014) 953–960. [14] K. Vlachos, M. Efremidis, K.P. Letsas, G. Bazoukis, R. Martin, M. Kalafateli, et al., Lowvoltage areas detected by high-density electroanatomical mapping predict recurrence after ablation for paroxysmal atrial fibrillation, J. Cardiovasc. Electrophysiol. (2017) https://doi.org/10.1111/jce.13321. [15] A. Verma, O.M. Wazni, N.F. Marrouche, D.O. Martin, F. Kilicaslan, S. Minor, R.A. Schweikert, W. Saliba, J. Cummings, J.D. Burkhardt, M. Bhargava, W.A. Belden, A. Abdul-Karim, A. Natale, Pre-existent left atrial scarring in patients undergoing pulmonary vein antrum isolation: an independent predictor of procedural failure, J. Am. Coll. Cardiol. 45 (2005) 285–292.