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Extent of Left Atrial Ablation Lesions and Atrial Fibrillation Recurrence after Catheter Ablation - A Systematic Review and Meta-Analysis

Abstract

Background:

Atrial fibrillation (AF) is known to induce atrial remodeling, which promotes fibrosis related to arrhythmogenesis. Accordingly, since scars induced by catheter ablation (CA) can reduce unablated fibrotic areas, greater extent of left atrial (LA) scarring may be associated with less AF recurrence after CA.

Objectives:

This study aims to investigate, through systematic review and meta-analysis, whether the amount of LA scarring, seen on late gadolinium enhancement magnetic resonance imaging, is associated with less AF recurrence after CA.

Methods:

The recommendations of the MOOSE guideline were followed. Database search was conducted in PubMed and Cochrane Central Register of Controlled Trials (comentário 1) until January 2019 (comentário 2). Two authors performed screening, data extraction, and quality evaluation. All studies were graded as good quality. A funnel plot was generated, showing no publication bias. Statistical significance was defined as p value < 0.05.

Results:

Eight observational studies were included in the systematic review, four of which were included in the meta-analysis. Six of the eight studies included in the systematic review showed that greater extension of LA scarring is associated with less AF recurrence after CA. Meta-analysis showed that greater extension of LA scarring is associated with less AF recurrence (SMD = 0.52; 95% CI 0.27 - 0.76; p < 0.0001).

Conclusion:

Greater extension of LA scarring is possibly associated with less AF recurrence after CA. Randomized studies that explore ablation methods based on this association are fundamental.

Keywords:
Atrial Fibrillation; Catheter Ablation; Heart Atria/injuries; Meta-Analysis as Topic; Databases,Bibliographic

Resumo

Fundamento:

A fibrilação atrial (FA) é conhecida por induzir o remodelamento atrial, que promove fibrose, provocando, por sua vez, mais arritmogênese. Dessa forma, visto que as cicatrizes induzidas pela ablação por cateter (AC) podem reduzir as áreas fibróticas, uma maior extensão de cicatrizes do átrio esquerdo (AE) pode estar associada a uma menor recorrência da FA após AC.

Objetivos:

Por meio de revisão sistemática e metanálise, o presente estudo visa investigar se a extensão total de cicatriz do AE, visualizada na ressonância magnética com realce tardio de gadolínio após a ablação, está associada a uma menor recorrência de FA após AC.

Métodos:

Foram seguidas as recomendações das diretrizes MOOSE. A busca foi realizada nas bases de dados PubMed e Cochrane Central Register of Controlled Trials até Janeiro de 2019. Dois autores realizaram triagem, extração de dados e avaliação da qualidade dos estudos. Em relação à qualidade, todos os estudos foram classificados como bons. Foi gerado um gráfico de funil, o qual não mostrou viés de publicação. Foi adotado nível de significância p < 0,05.

Resultados:

Oito estudos observacionais foram incluídos na revisão sistemática, dos quais quatro foram incluídos na metanálise. Dos oito estudos incluídos na revisão, seis mostraram que maior extensão de cicatrização do AE está associada a uma menor recorrência de FA após AC. A metanálise também demonstrou que maior extensão de cicatrização do AE está associada a uma menor recorrência de FA (SMD = 0,52; IC 95% 0,27 - 0,76; p < 0,0001).

Conclusão:

Uma maior extensão de cicatrização do AE está possivelmente associada a uma menor recorrência de FA após AC. Estudos randomizados que explorem métodos de ablação baseados nessa associação são fundamentais.

Palavras-chave:
Fibrilação Atrial; Ablação por Cateter; Átrios do Coração/lesões; Metanálise como Assunto; Base de Dados Bibliográficos

Introduction

Radiofrequency catheter ablation (RFCA) is a standard procedure for correction of atrial fibrillation (AF) in patients who have not responded to previous antiarrhythmic drug therapies.11 Wilber DJ, Pappone C, Neuzil P, De Paola A, Marchlinski F, Natale A, et al. Comparison of antiarrhythmic drug therapy and radiofrequency catheter ablation in patients with paroxysmal atrial fibrillation: a randomized controlled trial. JAMA. 2010;303(4):333-40. However, this procedure is related to high AF recurrence rates, even in the best hands.22 Weerasooriya R, Khairy P, Litalien J, Macle L, Hocini M, Sacher F, et al. Catheter ablation for atrial fibrillation: are results maintained at 5 years of follow-up? J Am Coll Cardiol. 2011;57(2):160-6. Accordingly, electrophysiologists and interventional cardiologists are seeking techniques that aim to reduce AF recurrence.

AF is known to induce atrial remodelling, increasing the amount of fibrotic tissue in the myocardium, which can promote atrial arrhythmogenesis, reinforcing the vicious cycle of AF.33 Burstein B, Nattel S. Atrial fibrosis: mechanisms and clinical relevance in atrial fibrillation. J Am Coll Cardiol. 2008;51(8):802-9.

4 Nattel S, Harada M. Atrial remodeling and atrial fibrillation: recent advances and translational perspectives. J Am Coll Cardiol. 2014;63(22):2335-45.
-55 Allessie MA, Konings K, Kirchhof CJ, Wijffels M. Electrophysiologic mechanisms of perpetuation of atrial fibrillation. Am J Cardiol. 1996;77(3):10A-23A. In this manner, since the scars induced by catheter ablation (CA) can reduce unablated fibrotic areas, the extent of the left atrial (LA) scars could be associated with less AF recurrence after CA. However, there are currently no systematic reviews or meta-analyses that have investigated this relationship, although they are the highest quality of evidence available.

Accordingly, this systematic review and meta-analysis aims to investigate if the amount of LA scarring, visualized by late gadolinium-enhanced magnetic resonance imaging (LGE-MRI), could be associated with less AF recurrence after CA, which can provide a solid background for designing new ablation strategies that improve patient outcomes.

Methods

A systematic review was performed according to the criteria established by the Meta-analysis of Observational Studies in Epidemiology (MOOSE) Group.66 Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283(15):2008-12.

Search strategies

Two investigators (ETOC and ETM) searched the PubMed and Cochrane Central Register of Controlled Trials, until January 2019. The search strategy comprised a combination of English terms and Medical Subject Headings (MeSH) descriptors, consisting of nine keywords [(left atrial OR left atrium) AND (scar OR scarring OR remodelling OR fibrosis OR enhancement) AND (ablation OR pulmonary vein isolation)]. A manual search of references was also used to identify possible studies for inclusion. Each title and abstract were independently analyzed by both investigators, who selected the articles which were relevant to the review. Subsequently, the full texts of the remaining articles were reviewed to select which would be included for qualitative or quantitative analysis. In the event of disagreement, the authors reached a decision through discussion and consensus.

Inclusion criteria for qualitative analysis

We included observational studies (with prospective or retrospective design) in humans, whose objective was to study the association between post-ablation LA scarring and AF recurrence after CA.

Studies that met the following criteria were included: 1) The study evaluated AF or total arrhythmia recurrence after CA in human subjects; 2) The publication was an original study; 3) The mean follow-up period was equal to or longer than 3 months; 4) The study included more than 20 subjects; 5) The study evaluated LA scarring by LGE-MRI after CA.

Inclusion criteria for quantitative analysis

Meta-analysis included studies that met the previous qualitative analysis criteria and reported means and 95% confidence intervals (CI) of total LA scarring in patients with and without AF recurrence after CA.

Quality assessment

Risk of bias in the studies was evaluated by the National Heart, Lung and Blood Institute Quality Assessment Tool for Case Series Studies.77 National Heart, Lung, and Blood Institute. Quality Assessment Tool for Case Series Studies [Internet]. Maryland, USA: NIH; 2019 [cited 12 out 2018]. Available from: https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools.
https://www.nhlbi.nih.gov/health-topics/...
Evaluation was independently conducted by two raters (ETOC and LMSB), and, in the event of disagreement, the raters reached a decision by consensus. The following characteristics were assessed: 1) Was the study question or objective clearly stated? 2) Was the study population clearly and fully described, including a case definition? 3) Were the cases consecutive? 4) Were the subjects comparable? 5) Was the intervention clearly described? 6) Were the outcome measures clearly defined, valid, reliable, and implemented consistently across all study participants? 7) Was the length of follow-up adequate? 8) Were the statistical methods well-described? 9) Were the results well described?

Following assessment of those characteristics, the authors assigned a quality rating (good, fair, or poor) to each of the studies. Studies were rated as ‘poor’ if they met fewer than three criteria; ‘fair’ if they met three to five criteria; and ‘good’ if they met more than five criteria. All studies selected met almost all of the criteria and received a good quality rating from both raters. Quality assessment of the included studies is reported in Table 1.

Table 1
Characteristics of the included studies and quality evaluation

Data extraction

Using a standard data extraction form, two researchers (ETOC and LMSB) performed data extraction, which was cross-verified by a third researcher (ETM). Extracted data included the following: 1) First author’s last name and publication year; 2) Characteristics of included studies: number of patients, study region, study design, ablation strategy, measurement method of LA scarring, method of AF detection, length of follow-up period, and main findings; 3) Outcome results: means and 95% CI of total LA scarring in patients with and without AF recurrence after CA.

Statistical analysis

The association between AF recurrence and total LA scarring following RFCA was measured by standardized mean difference (SMD) with 95% CI, and standard errors were determined using the corresponding 95% CI. The inverse variance method was used to weigh studies for combined statistical analysis. Statistical significance was defined as p value < 0.05. Heterogeneity between studies was assessed using Cochran’s Q test and I2 statistics and subsequently evaluated by I2 values. I2 values below 30% were defined as low heterogeneity; values between 30% and 60% were considered moderate heterogeneity; and values above 60% were considered high heterogeneity.88 Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539-58. The fixed-effects model was chosen due to the small number of studies included and the low heterogeneity. Meta-regression was not carried out due to the small number of studies included. The results are reported in a forest plot with 95% CI. Publication bias was verified using a funnel plot. All analyses were conducted using Review Manager 5.3 software.

Results

Study selection

Initially, a total of 790 studies were identified by the database search, 695 in PubMed and 95 in the Cochrane Central Register of Controlled Trials. Duplicate analysis revealed 28 duplicates, which were subsequently eliminated. After careful reading of the title and abstract, 742 of the 762 studies were excluded, because they were not related to the present review. Twenty studies were analyzed in full text, twelve of which were excluded, because they were not related to the present review. Finally, eight studies99 McGann CJ, Kholmovski EG, Oakes RS, Blauer JJ, Daccarett M, Segerson N, et al. New magnetic resonance imaging-based method for defining the extent of left atrial wall injury after the ablation of atrial fibrillation. J Am Coll Cardiol. 2008;52(15):1263-71.

10 Peters DC, Wylie JV, Hauser TH, Nezafat R, Han Y, Woo JJ, et al. Recurrence of atrial fibrillation correlates with the extent of post-procedural late gadolinium enhancement: a pilot study. JACC Cardiovasc Imaging. 2009;2(3):308-16.

11 Badger TJ, Daccarett M, Akoum NW, Adjei-Poku YA, Burgon NS, Haslam TS, et al. Evaluation of left atrial lesions after initial and repeat atrial fibrillation ablation: lessons learned from delayed-enhancement MRI in repeat ablation procedures. Circ Arrhythm Electrophysiol. 2010;3(3):249-59.

12 Akoum N, Daccarett M, McGann C, Segerson N, Vergara G, Kuppahally S, et al. 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(1):16-22.

13 McGann C, Kholmovski E, Blauer J, Vijayakumar S, Haslam T, Cates J, et al. Dark regions of no-reflow on late gadolinium enhancement magnetic resonance imaging result in scar formation after atrial fibrillation ablation. J Am Coll Cardiol. 2011;58(2):177-85.

14 Akoum N, Wilber D, Hindricks G, Jais P, Cates J, Marchlinski F, et al. MRI Assessment of ablation-induced scarring in atrial fibrillation: analysis from the DECAAF study. J Cardiovasc Electrophysiol. 2015;26(5):473-80.

15 Parmar BR, Jarrett TR, Kholmovski EG, Hu N, Parker D, MacLeod RS, et al. Poor scar formation after ablation is associated with atrial fibrillation recurrence. J Interv Card Electrophysiol. 2015;44(3):247-56.
-1616 Hunter RJ, Jones DA, Boubertakh R, Malcolme-Lawes LC, Kanagaratnam P, Juli CF, et al. Diagnostic accuracy of cardiac magnetic resonance imaging in the detection and characterization of left atrial catheter ablation lesions: a multicenter experience. J Cardiovasc Electrophysiol 2013;24(4):396-403. were included in the qualitative analysis, and four were included in the meta-analysis.99 McGann CJ, Kholmovski EG, Oakes RS, Blauer JJ, Daccarett M, Segerson N, et al. New magnetic resonance imaging-based method for defining the extent of left atrial wall injury after the ablation of atrial fibrillation. J Am Coll Cardiol. 2008;52(15):1263-71.

10 Peters DC, Wylie JV, Hauser TH, Nezafat R, Han Y, Woo JJ, et al. Recurrence of atrial fibrillation correlates with the extent of post-procedural late gadolinium enhancement: a pilot study. JACC Cardiovasc Imaging. 2009;2(3):308-16.
-1111 Badger TJ, Daccarett M, Akoum NW, Adjei-Poku YA, Burgon NS, Haslam TS, et al. Evaluation of left atrial lesions after initial and repeat atrial fibrillation ablation: lessons learned from delayed-enhancement MRI in repeat ablation procedures. Circ Arrhythm Electrophysiol. 2010;3(3):249-59.,1515 Parmar BR, Jarrett TR, Kholmovski EG, Hu N, Parker D, MacLeod RS, et al. Poor scar formation after ablation is associated with atrial fibrillation recurrence. J Interv Card Electrophysiol. 2015;44(3):247-56. The study selection flow diagram is shown in Figure 1.

Figure 1
Study selection flow diagram.

Characteristics of the included studies

Eight studies were included in this review,99 McGann CJ, Kholmovski EG, Oakes RS, Blauer JJ, Daccarett M, Segerson N, et al. New magnetic resonance imaging-based method for defining the extent of left atrial wall injury after the ablation of atrial fibrillation. J Am Coll Cardiol. 2008;52(15):1263-71.

10 Peters DC, Wylie JV, Hauser TH, Nezafat R, Han Y, Woo JJ, et al. Recurrence of atrial fibrillation correlates with the extent of post-procedural late gadolinium enhancement: a pilot study. JACC Cardiovasc Imaging. 2009;2(3):308-16.

11 Badger TJ, Daccarett M, Akoum NW, Adjei-Poku YA, Burgon NS, Haslam TS, et al. Evaluation of left atrial lesions after initial and repeat atrial fibrillation ablation: lessons learned from delayed-enhancement MRI in repeat ablation procedures. Circ Arrhythm Electrophysiol. 2010;3(3):249-59.

12 Akoum N, Daccarett M, McGann C, Segerson N, Vergara G, Kuppahally S, et al. 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(1):16-22.

13 McGann C, Kholmovski E, Blauer J, Vijayakumar S, Haslam T, Cates J, et al. Dark regions of no-reflow on late gadolinium enhancement magnetic resonance imaging result in scar formation after atrial fibrillation ablation. J Am Coll Cardiol. 2011;58(2):177-85.

14 Akoum N, Wilber D, Hindricks G, Jais P, Cates J, Marchlinski F, et al. MRI Assessment of ablation-induced scarring in atrial fibrillation: analysis from the DECAAF study. J Cardiovasc Electrophysiol. 2015;26(5):473-80.

15 Parmar BR, Jarrett TR, Kholmovski EG, Hu N, Parker D, MacLeod RS, et al. Poor scar formation after ablation is associated with atrial fibrillation recurrence. J Interv Card Electrophysiol. 2015;44(3):247-56.
-1616 Hunter RJ, Jones DA, Boubertakh R, Malcolme-Lawes LC, Kanagaratnam P, Juli CF, et al. Diagnostic accuracy of cardiac magnetic resonance imaging in the detection and characterization of left atrial catheter ablation lesions: a multicenter experience. J Cardiovasc Electrophysiol 2013;24(4):396-403. comprising six prospective single center observational studies and two prospective multicenter studies (Table 1). The systematic review included a total of 703 patients, and meta-analysis included 295. The follow-up period ranged from 3 to 12 months. All studies used LGE-MRI to identify post-CA LA scarring. Pulmonary vein isolation (PVI) was the ablation strategy in all of the studies. The studies by Akoum et al.1414 Akoum N, Wilber D, Hindricks G, Jais P, Cates J, Marchlinski F, et al. MRI Assessment of ablation-induced scarring in atrial fibrillation: analysis from the DECAAF study. J Cardiovasc Electrophysiol. 2015;26(5):473-80. and Hunter et al.1616 Hunter RJ, Jones DA, Boubertakh R, Malcolme-Lawes LC, Kanagaratnam P, Juli CF, et al. Diagnostic accuracy of cardiac magnetic resonance imaging in the detection and characterization of left atrial catheter ablation lesions: a multicenter experience. J Cardiovasc Electrophysiol 2013;24(4):396-403. used both catheter and cryoballoon ablation. Table 1 and Table 2 summarize the characteristics of all included studies.

Table 2
Characteristics of the included studies and main findings

Total LA scarring post-ablation and AF recurrence

Six of the eight included studies88 Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539-58.

9 McGann CJ, Kholmovski EG, Oakes RS, Blauer JJ, Daccarett M, Segerson N, et al. New magnetic resonance imaging-based method for defining the extent of left atrial wall injury after the ablation of atrial fibrillation. J Am Coll Cardiol. 2008;52(15):1263-71.

10 Peters DC, Wylie JV, Hauser TH, Nezafat R, Han Y, Woo JJ, et al. Recurrence of atrial fibrillation correlates with the extent of post-procedural late gadolinium enhancement: a pilot study. JACC Cardiovasc Imaging. 2009;2(3):308-16.

11 Badger TJ, Daccarett M, Akoum NW, Adjei-Poku YA, Burgon NS, Haslam TS, et al. Evaluation of left atrial lesions after initial and repeat atrial fibrillation ablation: lessons learned from delayed-enhancement MRI in repeat ablation procedures. Circ Arrhythm Electrophysiol. 2010;3(3):249-59.
-1212 Akoum N, Daccarett M, McGann C, Segerson N, Vergara G, Kuppahally S, et al. 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(1):16-22.,1414 Akoum N, Wilber D, Hindricks G, Jais P, Cates J, Marchlinski F, et al. MRI Assessment of ablation-induced scarring in atrial fibrillation: analysis from the DECAAF study. J Cardiovasc Electrophysiol. 2015;26(5):473-80. found that the extent of LA scarring was associated with less AF recurrence after CA.

In the study by Hunter et al.,1616 Hunter RJ, Jones DA, Boubertakh R, Malcolme-Lawes LC, Kanagaratnam P, Juli CF, et al. Diagnostic accuracy of cardiac magnetic resonance imaging in the detection and characterization of left atrial catheter ablation lesions: a multicenter experience. J Cardiovasc Electrophysiol 2013;24(4):396-403. there was no significant association between identification of ablation lesions and freedom from AF (53% with ablation lesions identified remained free from AF vs. 65% in those with no lesions identified, p = 0.560). The study also performed binary logistic regression, which confirmed that there was no significant association between identification of ablation lesions and freedom from AF.1616 Hunter RJ, Jones DA, Boubertakh R, Malcolme-Lawes LC, Kanagaratnam P, Juli CF, et al. Diagnostic accuracy of cardiac magnetic resonance imaging in the detection and characterization of left atrial catheter ablation lesions: a multicenter experience. J Cardiovasc Electrophysiol 2013;24(4):396-403.

The 2015 study by Akoum et al.1414 Akoum N, Wilber D, Hindricks G, Jais P, Cates J, Marchlinski F, et al. MRI Assessment of ablation-induced scarring in atrial fibrillation: analysis from the DECAAF study. J Cardiovasc Electrophysiol. 2015;26(5):473-80. found that ablation-induced scarring was not a statistically significant predictor of less AF recurrence (hazard ratio = 0.95; p = 0.097). However, according to this same study, when performing scar homogenization, inducing ablation lesions in prior fibrotic tissue leads to a lower recurrence rate, because less heterogeneous fibrotic tissue remains.1414 Akoum N, Wilber D, Hindricks G, Jais P, Cates J, Marchlinski F, et al. MRI Assessment of ablation-induced scarring in atrial fibrillation: analysis from the DECAAF study. J Cardiovasc Electrophysiol. 2015;26(5):473-80.

Meta-analysis

The present meta-analysis shows that total LA scarring post-ablation is associated with less AF recurrence after CA (SMD = 0.52, 95% CI 0.27 - 0.76, p < 0.0001), as shown in Figure 2. The heterogeneity test showed that there were no significant differences between studies (p = 0.4, I2 = 0%). A funnel plot (Figure 3) was used to verify the existence of publication bias. There was no obvious asymmetry, suggesting that there was no publication bias.

Figure 2
Forest plot showing that the extent of left atrial scarring is associated with less atrial fibrillation recurrence after catheter ablation.

CI: confidence interval; IV: inverse variance


Figure 3
Funnel plot showing no publication bias.

Discussion

The importance of CA for AF correction has grown since its introduction. A recent meta-analysis by Kheiri et al. that included seven randomized controlled trials showed that CA was associated with better outcomes in patients with AF and heart failure, in comparison with medical treatment.1717 Kheiri B, Osman M, Abdalla A, Haykal T, Ahmed S, Bachuwa G, et al. Catheter ablation of atrial fibrillation with heart failure: An updated meta-analysis of randomized trials. Int J Cardiol. 2018 Oct 15;269:170-3. Therefore, interventional cardiologists should seek ablation strategies that reduce AF recurrence and procedural risks. This systematic review and meta-analysis shows that the extent of LA scarring after ablation is possibly associated with less AF recurrence after CA, paving the way for future research on ablation methods with lower chances of post-procedural recurrence.

Substrate modification

Previous studies in animal models have established the concept that “AF begets AF” by atrial remodeling.1818 Wijffels MC, Kirchhof CJ, Dorland R, Allessie MA. Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats. Circulation. 1995;92(7):1954-68. In this manner, AF stimulates atrial fibrotic alterations that maintain and increase the AF burden, leading to a vicious cycle.1919 Li D, Fareh S, Leung TK, Nattel S. Promotion of atrial fibrillation by heart failure in dogs: atrial remodeling of a different sort. Circulation. 1999;100(1):87-95. Furthermore, in spite of some limitations, studies in humans have shown that patients with paroxysmal AF have increased LA stiffness, possibly due to an increase in LA fibrosis.2020 Yoon YE, Kim HJ, Kim SA, Kim SH, Park JH, Park KH, et al. Left atrial mechanical function and stiffness in patients with paroxysmal atrial fibrillation. J Cardiovasc Ultrasound. 2012;20(3):140-5.,2121 Ágoston G, Szilágyi J, Bencsik G, Tutuianu C, Klausz G, Sághy L, et al. Impaired adaptation to left atrial pressure increase in patients with atrial fibrillation. J Interv Card Electrophysiol. 2015;44(2):113-8.

In addition to that, animal studies have demonstrated that 80% of AF triggers are located in the posterior wall, including the pulmonary vein (PV) region.2222 Sánchez-Quintana D, López-Mínguez JR, Pizarro G, Murillo M, Cabrera JA. Triggers and anatomical substrates in the genesis and perpetuation of atrial fibrillation. Curr Cardiol Rev. 2012;8(4):310-26. A previous meta-analysis has shown that isolation of a part of the posterior LA reduces the recurrence of AF after CA.2323 He X, Zhou Y, Chen Y, Wu L, Huang Y, He J. Left atrial posterior wall isolation reduces the recurrence of atrial fibrillation: a meta-analysis. J Interv Card Electrophysiol. 2016;46(3):267-74. Therefore, an increase in the extent of LA ablation may promote greater substrate modification, decreasing the amount of viable LA tissue capable of harboring AF by overlapping PV and non-PV triggers with ablation lesions.

PV scarring

The clinical application of real-time MRI may make it possible to visualize LA scarring during the procedure, making it easier to induce scarring.2424 Eitel C, Hindricks G, Grothoff M, Gutberlet M, Sommer P. Catheter ablation guided by real-time MRI. Curr Cardiol Rep. 2014;16(8):511. However, as real-time MRI is still a new and expensive imaging method, alternatives such as driver-guided CA by electroanatomic mapping to visualize LA scars might be an option for optimizing outcomes. A recent meta-analysis by Ramirez et al.2525 Ramirez FD, Birnie DH, Nair GM, Szczotka A, Redpath CJ, Sadek MM, et al. Efficacy and safety of driver-guided catheter ablation for atrial fibrillation: a systematic review and meta-analysis. J Cardiovasc Electrophysiol. 2017;28(12):1371-8. reported an association between driver-guided CA for AF and increased freedom from AF, in comparison with conventional strategies. However, this meta-analysis included primarily nonrandomized studies of moderate quality. Future observational studies can help build evidence to prove whether electroanatomic mapping can assist in creating contiguous scar lesions around the PV.

Risks of targeting more LA scarring

Even though this meta-analysis shows that more extensive ablation reduces the risk of AF recurrence, this strategy is not risk free, given that the procedure may decrease LA compliance, LA volume, and LA systolic function, which may induce the development of the stiff left atrial syndrome (SLAS).2626 Phung TN, Moyer CB, Norton PT, Ferguson JD, Holmes JW. Effect of ablation pattern on mechanical function in the atrium. Pacing Clin Electrophysiol. 2017;40(6):648-54. SLAS, which was described in 1988 by Pilote et al.,2727 Pilote, L, Hüttner I, Marpole D, Sniderman A. Stiff left atrial syndrome. Can J Cardiol. 1988;4(6):255-7. is characterized by a decline in LA diastolic function and pulmonary hypertension.2828 Gibson DN, Di Biase L, Mohanti P, Patel JD, Bai R, Sanchez J, et al: Stiff left atrial syndrome after catheter ablation for atrial fibrillation: clinical characterization, prevalence, and predictors. Heart Rhythm. 2011;8(9):1364-71. Although this may represent a severe consequence of RFCA, in a case series study by Gibson et al., the condition was reported in only 1.4% of patients who underwent RFCA.2828 Gibson DN, Di Biase L, Mohanti P, Patel JD, Bai R, Sanchez J, et al: Stiff left atrial syndrome after catheter ablation for atrial fibrillation: clinical characterization, prevalence, and predictors. Heart Rhythm. 2011;8(9):1364-71.

Furthermore, previous studies found that LA scar volume after CA was associated with depressed LA systolic function.2626 Phung TN, Moyer CB, Norton PT, Ferguson JD, Holmes JW. Effect of ablation pattern on mechanical function in the atrium. Pacing Clin Electrophysiol. 2017;40(6):648-54.,2929 Wylie JV, Peters DC, Essebag V, Manning WJ, Josephson ME, Hauser TH. Left atrial function and scar after catheter ablation of atrial fibrillation. Heart Rhythm. 2008;5(5):656-62. Ablation scars in the posterior LA wall, however, had less effect on LA systolic function.2626 Phung TN, Moyer CB, Norton PT, Ferguson JD, Holmes JW. Effect of ablation pattern on mechanical function in the atrium. Pacing Clin Electrophysiol. 2017;40(6):648-54.

Another risk of CA that extensive ablation may increase is the possibility of esophageal injury due to the anatomical relationship between the esophagus and the posterior LA wall.2929 Wylie JV, Peters DC, Essebag V, Manning WJ, Josephson ME, Hauser TH. Left atrial function and scar after catheter ablation of atrial fibrillation. Heart Rhythm. 2008;5(5):656-62. The esophagus is separated from the posterior LA by a thin layer of fat, being prone to injury during AF ablation.3030 Sandhu A, Zipse MM, Borne RT, Aleong RG, Tompkins C, Schuller J, et al. Esophageal position, measured luminal temperatures, and risk of atrioesophageal fistula with atrial fibrillation ablation. Pacing Clin Electrophysiol. 2019;42(4):458-63. Possible esophageal injuries include perforation, atrio-esophageal fistula formation, and peri-esophageal nerve injury.3030 Sandhu A, Zipse MM, Borne RT, Aleong RG, Tompkins C, Schuller J, et al. Esophageal position, measured luminal temperatures, and risk of atrioesophageal fistula with atrial fibrillation ablation. Pacing Clin Electrophysiol. 2019;42(4):458-63. To minimize the potential risks of esophageal injuries, strategies, such as reducing power in the posterior LA wall, monitoring temperature in the esophagus, irrigating the esophagus with cold water, and pre-procedural imaging, should be adopted.3131 Aupperle H, Doll N, Walther T, Kornherr P, Ullmann C, Schoon HA, et al. Ablation of atrial fibrillation and esophageal injury: effects of energy source and ablation technique. J Thorac Cardiovasc Surg. 2005;130(6):1549-54.

32 Medeiros De Vasconcelos JT, Filho SDSG, Atié J, Maciel W, De Souza OF, Saad EB, et al. Atrial-oesophageal fistula following percutaneous radiofrequency catheter ablation of atrial fibrillation: the risk still persists. Europace. 2017;19(2):250-8.
-3333 Scanavacca M. Current atrial fibrillation ablation: an alert for the prevention and treatment of esophageal lesions. Arq Bras Cardiol. 2016;106(5):354-7.

Reproducibility

A previous study by Chubb et al.,3434 Chubb H, Karim R, Roujol S, Nuñez-Garcia M, Williams SE, Whitaker J, et al. The reproducibility of late gadolinium enhancement cardiovascular magnetic resonance imaging of post-ablation atrial scar: a cross-over study. J Cardiovasc Magn Reson. 2018;20(1):21. which investigated post-ablation atrial scar, using LGE-MRI, in 40 subjects undergoing first time ablation for AF, showed that post-ablation visualization of induced scars in the LA is reproducible. Moreover, they concluded that imaging should be performed at least 20 minutes after administration of gadolinium-based contrast for better reproducibility.3434 Chubb H, Karim R, Roujol S, Nuñez-Garcia M, Williams SE, Whitaker J, et al. The reproducibility of late gadolinium enhancement cardiovascular magnetic resonance imaging of post-ablation atrial scar: a cross-over study. J Cardiovasc Magn Reson. 2018;20(1):21. However, the study by Hunter et al. analyzed in the present review, which included 50 patients, concluded that LGE imaging of atrial scar is not yet sufficiently accurate to identify ablation lesions or determine lesion distribution reliably. A published consensus by the European Heart Rhythm Association stated that there is still neither recommendation nor expert consensus on the role of LGE-MRI to assist AF ablation procedures. The consensus, nevertheless, states that the available data are intriguing enough to warrant further research.3535 Donal E, Lip GY, Galderisi M, Goette A, Shah D, Marwan M, et al. EACVI/EHRA Expert Consensus Document on the role of multi-modality imaging for the evaluation of patients with atrial fibrillation. Eur Heart J Cardiovasc Imaging. 2016;17(4):355-83.

STAR AF II and DECAAF II

Although previous studies have demonstrated the positive impact of targeting ablation strategies beyond circumferential pulmonary vein isolation (CPVI), the STAR AF II trial showed a different scenario.2323 He X, Zhou Y, Chen Y, Wu L, Huang Y, He J. Left atrial posterior wall isolation reduces the recurrence of atrial fibrillation: a meta-analysis. J Interv Card Electrophysiol. 2016;46(3):267-74.,3636 Verma A, Jiang CY, Betts TR, Chen J, Deisenhofer I, Mantovan R, et al. Approaches to catheter ablation for persistent atrial fibrillation. N Engl J Med. 2015;372(19):1812-22. The STAR AF II was a randomized multicenter study, which, in patients with persistent AF, compared CPVI alone, CPVI plus linear ablation across the LA roof and mitral valve isthmus, and CPVI plus ablation of complex fractionated electrograms. No reduction was found in the recurrence of AF when additional strategies beyond CPVI were performed.3636 Verma A, Jiang CY, Betts TR, Chen J, Deisenhofer I, Mantovan R, et al. Approaches to catheter ablation for persistent atrial fibrillation. N Engl J Med. 2015;372(19):1812-22.

The DECAAF study showed that LA fibrosis visualized by LGE-MRI was a strong predictor of ablation outcome, and the more ablation-induced scarring overlapped fibrotic tissue, the better the outcome.3737 Marrouche NF, Wilber D, Hindricks G, Jais P, Akoum N, Marchlinski F, et al. Association of atrial tissue fibrosis identified by delayed enhancement MRI and atrial fibrillation catheter ablation: the DECAAF study. JAMA. 2014;311(5):498-506. Accordingly, the DECAAF II study will randomize patients with persistent AF to receive either conventional PVI ablation or PVI guided by LGE-MRI.3838 National Heart, Lung, and Blood Institute. ClinicalTrials.gov [Internet]. Efficacy of Delayed Enhancement MRI-Guided Ablation vs Conventional Catheter Ablation of Atrial Fibrillation (DECAAFII). Maryland, USA: NIH; 2019 [cited 17 fev 2018].Available from: https://clinicaltrials.gov/ct2/show/NCT02529319.
https://clinicaltrials.gov/ct2/show/NCT0...

Future studies

The increased use of CA for AF correction in clinical practice requires better strategies to reduce post procedural failures. It is necessary to conduct randomized controlled trials that compare driver-guided CA by electroanatomic mapping with traditional ablation methods. Moreover, it is important to standardize LGE-MRI to detect LA scars in order to guarantee its reproducibility. In addition to that, developing real-time MRI on a larger scale might reduce its costs, making it possible to use in the future.

Limitations

Although the present systematic review and meta-analysis provides a significant increase in the number of patients analyzed, the number of patients included is limited. Moreover, only four studies were included in the quantitative analysis, and all of them were observational studies. Although LGE-MRI is feasible to detect post-ablation atrial scar, its reproducibility needs to be further studied.

Conclusion

The present review shows that the extent of post-ablation LA scars is possibly associated with less AF recurrence after CA (SMD = 0.52; 95% CI 0.27 - 0.76; p < 0.0001), which paves the way for scar-guided ablation strategies. However, the reproducibility of this imaging method needs to be further studied and improved. It is necessary to conduct randomized controlled trials, such as the DECAAF II trial, that investigate ablation methods based on this association in order to provide patients with the best treatment option, with minimal risk of AF recurrence and complications.

  • Sources of Funding
    There were no external funding sources for this study.
  • Study Association
    This study is not associated with any thesis or dissertation work.
  • Ethics approval and consent to participate
    This article does not contain any studies with human participants or animals performed by any of the authors.

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    » https://clinicaltrials.gov/ct2/show/NCT02529319

Publication Dates

  • Publication in this collection
    14 Feb 2020
  • Date of issue
    Apr 2020

History

  • Received
    26 Nov 2018
  • Reviewed
    29 Apr 2019
  • Accepted
    05 June 2019
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