Abstract
Background
The anatomic ablation set that comprises pulmonary vein isolation, roof line, posterior mitral line with vein of Marshall alcohol ablation, and cavotricuspid isthmus line spares the anterior wall to preserve left atrial (LA) physiology. The outcome of patients with persistent atrial fibrillation (AF) and spontaneous LA anterior scar ablated with this strategy is not known.
Objective
This study aimed to evaluate patients presenting with spontaneous LA anterior scar and persistent AF in terms of clinical characteristics and ablation outcome using this ablation set.
Methods
Patients with persistent AF referred for AF ablation from June 2018 to June 2023 were screened. Patients presenting spontaneous LA anterior scar were compared with patients with no scar. The ablation strategy consisted of pulmonary vein isolation, vein of Marshall alcohol ablation, roof line, posterior mitral line, and cavotricuspid isthmus line.
Results
111 consecutive patients were evaluated: 35 patients in the scar group (SCAR group) and 76 patients in the control group. After propensity weighting, the population resulted in 101 patients: 34 patients in the SCAR group and 67 patients in the control group. There were significantly more female patients in the SCAR group (18 [23.4%] vs 20 [69%]; P < .001). The mean follow-up was 17 ± 11 months. The lesion set could be accomplished in all. After a first procedure, the AT-AF-free survival was significantly lower in the SCAR group (82.9% vs 65.7%; P = .005).
Conclusion
After a Marshall-plan ablation procedure, the presence of spontaneous LA anterior scar is associated with more AT/AF recurrence during the follow-up. These results suggest that additional ablation may be necessary to complement the initial ablation set during the first procedure in these patients.
Keywords: Left atrium, Anterior scar, Persistent atrial fibrillation, Catheter ablation, Marshall plan
Key Findings.
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▪
Anterior left atrial scar is associated with a specific patient phenotype.
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Spontaneous left atrial anterior scarring is associated with a significantly lower arrhythmia-free survival rate at 12 months after the first atrial fibrillation ablation procedure than patients without scar (65.7% vs 82.9%; P = .0038).
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▪
The presence of left atrial anterior scar is an independent predictor of arrhythmia recurrence, even after adjusting for confounders (hazard ratio 1.29, P = .015).
Introduction
Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting millions of individuals worldwide.1 Persistent AF (P-AF), defined as AF lasting more than 7 days or requiring intervention to terminate, is particularly challenging to treat because of the progression of atrial remodeling and fibrosis, which create a complex arrhythmogenic substrate. Among the risk factors for P-AF, atrial fibrosis is recognized as a key pathophysiological mechanism, and its presence often correlates with worse procedural outcomes after catheter ablation.2
Spontaneous atrial scarring, characterized by areas of low voltage on electroanatomic mapping, has been identified in some patients with P-AF even in the absence of structural heart disease or heart failure.3 This phenomenon is poorly understood but suggests a distinct patient phenotype with potential implications for ablation strategies. Preexisting atrial scars contribute to arrhythmogenesis by fostering reentrant circuits and creating conduction delays.
The lesion set, including pulmonary vein isolation (PVI), roof line, posterior mitral line, vein of Marshall (VOM) alcohol ablation, and cavotricuspid isthmus (CTI) line, is an anatomy-based ablation strategy.4 It intentionally spares the anterior wall of the left atrium (LA), a region critical to maintaining atrial contractile function. By preserving this area, the strategy aims to minimize disruption to LA physiology while still achieving durable arrhythmia control.5 Previous studies have demonstrated an 85% arrhythmia-free survival rate at 12 months with this approach, highlighting its efficacy in patients with P-AF.5
Given the potential impact of anterior scarring on procedural outcomes, it is critical to evaluate whether the standard ablation strategy is sufficient for this subgroup of patients. This study aimed to address this gap by comparing baseline characteristics, procedural outcomes, and arrhythmia recurrence rates in patients with and without spontaneous anterior LA scarring who underwent ablation using this standard ablation strategy.
Methods
This study conforms to the guiding principles of the Declaration of Helsinki and has been approved by our Institutional Committee on Human Research. All patients gave their written consent.
Patient selection
The electronic medical database of our institute was screened for patients referred for AF ablation from June 2018 to June 2023. Patients ablated with the complete lesion set with and without LA scar were included. An anterior scar of ≥5 cm2 was considered significant for inclusion in the study.5 AF was diagnosed on a 12-lead electrocardiography. A history of CTI ablation was accepted if not associated with LA ablation. Exclusion criteria were as follows: history of AF ablation, severe valvular disease, and hypertrophic cardiomyopathy. Clinical data included arrhythmia history, physical examination, and transthoracic echocardiography.
Mapping and ablation protocol
Procedures were performed under conscious sedation with the CARTO 3 system (Biosense Webster). The ablation set has previously been described.4 Briefly, 3 catheters were inserted via 3 right femoral vein punctures: (1) a steerable decapolar catheter (Dynamic XT, Boston Scientific) in the coronary sinus (CS), (2) a 3.5-mm irrigated tip catheter (ThermoCool SmartTouch, Biosense Webster) for ablation, and (3) a multipolar catheter (PentaRay or OctaRay, Biosense Webster) to perform the LA anatomic shell reconstruction and electrogram recording.
The following steps were performed: (1) VOM alcohol ablation: after CS cannulation (steerable sheath, left internal mammary artery catheter), contrast was injected to localize the VOM. A preloaded angioplasty balloon (Mini Trek, length 6–8 mm, nominal diameter 2–3.5 mm; Abbott) with an angioplasty guidewire (Hi-Torque Whisper MS; Abbott) was advanced into the VOM near its ostium. A total of 10 mL of 96% ethanol was infused (3 separate 1-minute injections). Ethanol infusion was considered successful if repeat angiograms between the 3 injections demonstrated complete occlusion of the vessel by the angioplasty balloon without contrast leakage back into the CS, stability of the angioplasty balloon, visualization of the distal VOM arborization, and absence or limited dissection of the VOM. (2) PVI: wide antral PVI was performed. (3) Atrial lines completion: mitral (between the mitral annulus and the left inferior pulmonary vein [PV]), with systematic ablation of the atrial aspect of the CS in front of the endocardial line (including the low voltage induced by VOM ethanol infusion [VOM-OH]), roof line, and CTI line. The LA appendage activation was studied before the completion of the mitral line to ensure anterior activation. The ablation technique was point by point using power-control mode and irrigation between 8 and 20 mL/min. For each ablation point, radiofrequency current was delivered for 10–30 seconds with a power of 20–25 W in the CS, 30–50 W posteriorly, and 40–50 W at other sites. Real-time automated display of each radiofrequency application (VisiTag) was systematic, using the following parameters: catheter stability of ≤2 mm during 4 seconds; minimum force of 8 g for 70% of the radiofrequency application. Ablation index was then monitored to adjust application duration with the aim of 400–450 at the posterior wall and 550–600 at the anterior wall. At the end of these 3 steps, if AF was still present, an electrical cardioversion was performed to restore sinus rhythm and to assess PVI and line block. To that purpose, a high-density map during left appendage pacing, in addition to overlap pacing and PV pacing to confirm PVI and conduction blocks on the lines, was conducted. In the case of residual conduction across the roof line, a floor line was performed. In the case of residual conduction across the mitral line, more ablation was performed based on the activation map (including CS free wall ablation if required) (Figure 1).
Figure 1.
Kaplan-Meier curve of AT/AF event-free survival after the first procedure (days). AF = atrial fibrillation; AT = atrial tachycardia.
Low-voltage electrograms were defined as an amplitude of <0.2 mV in sinus or paced rhythms and <0.05 mV in AF, and the noise threshold was 0.03 mV. Signals were recorded in bipolar mode at the maximum amplitude in the window. The point filtering parameter of internal points was set at 7. The minimal surface area considered for a significant scar was 5 cm2.6
Follow-up
The follow-up was scheduled at 3, 6, and 12 months and at least once a year thereafter. This evaluation included (1) a clinical examination assessing AF-related symptoms, New York Heart Association class, and other heart failure signs; (2) cardiac implantable electronic device interrogation when relevant; (3) a 12-lead electrocardiography; and (4) transthoracic echocardiography assessing left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter, aorta measurements, LA volume, and transmitral pulsed Doppler assessment. Recurrences were defined as sustained (>30 seconds) symptomatic or asymptomatic atrial tachycardia (AT) or AF. They were also classified as occurring before or after a 3-month blanking period after ablation, complying with the guidelines.
Statistical analysis
Continuous variables are presented as mean (standard error). Categorical variables are presented as proportions and percentages.
To compare the occurrence of AF and AT across time, the inverse probability of treatment weighting (IPTW) methodology was used to adjust for measured confounding between both groups (with and without cardiac scar). A binomial generalized linear model with a logit link was fitted to estimate the propensity score (ie, probability) that a patient presented with an anterior scar. The following variables were used as predictors: adjusted aorta dimensions, sex, body mass index (BMI), body surface area, hypertension, LVEF, and continuous AF duration. LA volume was positively correlated with continuous AF duration, so only the latter was used in the model. Then stabilized weights were calculated as follows: (proportion with scar) / propensity score for the scar group (SCAR group) and (proportion without scar) / (1-propensity score) propensity score for the unexposed group.
Determinants of adverse outcomes at follow-up (ie, AF and AT) were analyzed by regression analysis using the weighted Cox proportional hazard model. We started from an initial model including the following predictors: age, CHADS-VASc score, occurrence of scar, adjusted aorta dimensions, sex, BMI, body surface area, hypertension, LVEF, LA volume index, and continuous AF duration. Then we conducted a stepwise backward regression based on the Akaike information criterion. Model assumptions were checked; more precisely, Schoenfeld residuals were used to assess the proportional hazards assumption, and martingale residuals were used to assess the linearity assumption for continuous variables. If needed, continuous features were transformed into categorical features as recommended. All hazard ratios (HRs) are provided along with 95% confidence intervals.
Survival curves (ie, time to event) for AF and AT were generated using the Kaplan-Meier method.
Statistical significance was defined as P < .05. All analyses were conducted using R V4.1.
Results
Study population
A total of 111 consecutive patients referred for P-AF ablation using the standard lesion strategy between June 2018 and June 2023 were screened for inclusion. Of these, 35 patients were identified as having spontaneous LA anterior scar (SCAR group), whereas 76 patients had no evidence of anterior scarring (N-scar group). After applying IPTW to balance baseline characteristics, the final weighted cohort included 101 patients: 34 in the SCAR group and 67 in the N-scar group.
Baseline characteristics are presented in Table 1. Patients in the SCAR group were significantly more likely to be female (58.8% vs 23.4%; P < .001). The SCAR group also exhibited a trend toward older age (68.7 ± 8.3 years vs 64.5 ± 10.5 years; P = .056) and had higher CHADS-VASc scores (3.4 ± 1.7 vs 2.5 ± 1.6; P = .017). In addition, continuous AF duration was significantly longer in the SCAR group than the N-scar group (9.8 ± 19.3 months vs 3.2 ± 2.4 months; P = .006), and LA volume (mL/m2) was larger (SCAR 46 ± 13 vs N-scar 37.5 ± 16.5). Importantly, no significant differences were observed between the 2 groups in terms of LVEF, BMI, or history of hypertension (Table 1).
Table 1.
Characteristics of the patient population
| Characteristics | N-scar (n = 67) | SCAR (n = 34) | P value |
|---|---|---|---|
| Sex, female, n (%) | 15 (22.4) | 20 (58.8) | <.01 |
| Age, y (±SD) | 64.5 (±10.5) | 68.7 (±8.3) | .05 |
| Continuous AF duration, mo (±SD) | 3.2 (± 2.4) | 9.8 (±19.3) | .01 |
| Symptoms, n (%) | 54 (81.8) | 31 (91.2) | .21 |
| History of cardioversion, n (%) | 46 (68.6) | 22 (64.7) | .69 |
| BMI, kg/m2 (±SD) | 28.12 (±5.8) | 26.92 (±6) | .19 |
| CHADS-VASc score, mean (±SD) | 2.52 (±1.6) | 3.38 (±1.7) | .02 |
| Heart failure, n (%) | 38 (56.7) | 13 (38.2) | .08 |
| Hypertension, n (%) | 34 (50.7) | 18 (52.9) | .83 |
| Diabetes, n (%) | 10 (15) | 6 (17.6) | .72 |
| Stroke, n (%) | 6 (8.9) | 8 (23.5) | .06 |
| Dilated cardiomyopathy, n (%) | 7 (10.4) | 3 (8.8) | .44 |
| Ischemic heart disease, n (%) | 16 (23.8) | 10 (29.4) | .55 |
| LVEF, mean (±SD) | 59.2 (±9) | 58.5 (±11) | .67 |
| LA volume index, mL/m2 (±SD) | 37.5 (±16.5) | 46 (±13) | <.01 |
AF = atrial fibrillation; BMI = body mass index; LA = left atrial; LVEF = left ventricular ejection fraction; N-scar = control group; SCAR = scar group; SD = standard deviation.
Procedural characteristics
The analysis was performed on the whole cohort. Baseline rhythm during LA mapping was comparable between the groups (AF in 23 patients in the SCAR group [67.5%] and 35 patients in the N-scar group [52.2%]; P = .23). Conduction block was confirmed in 97.4% of the SCAR group and 86.6% of the N-scar group (P = .09). Residual gaps, when present, were located at the dome (5 vs 2 patients; P > .99), mitral isthmus (6 vs 2 patients; P > .99), or CTI line (1 vs 0 patients; P > .99), with no significant differences between groups
In the SCAR group, the mean surface area of the low-voltage anterior atrial scar was measured at 16.27 cm2 (±8.29), illustrating the extent of fibrosis in these patients. In spite of this anterior scar, the LA appendage was activated by the Bachman bundle in all cases, enabling the completion of the posterior mitral line. The mean procedural duration was comparable between groups (P = .79) (Table 2).
Table 2.
Procedural data for the first procedure
| Procedural data | N-scar (n = 67) | SCAR (n = 34) | P value |
|---|---|---|---|
| Baseline rhythm during mapping: atrial fibrillation, n (%) | 35 (52.2) | 23 (67.6) | .23 |
| Point density of the maps, mean (±SD) | 5810 (±6875) | 8840 (±7245) | .10 |
| Blocked Marshall set, n (%) | 58 (86.6) | 33 (97) | .16 |
| Anterior scar surface area, cm2 (±SD) | 0 | 16.27 (±8.3) | |
| Spontaneous anterior atrial tachycardia, n (%) | 0 | 1 (2.9) | .34 |
| Induced anterior atrial tachycardia, n (%) | 0 | 0 | |
| Mitral gap, n (%) | 0 | 0 | |
| Dome gap, n (%) | 5 (7.4) | 2 (5.8) | >.99 |
| CTI gap, n (%) | 1 (1.5) | 0 | >.99 |
| Ablation duration, min (±SD) | 42.7 (±11.2) | 42.7 (±9.3) | .79 |
| Fluoroscopy duration, min (±SD) | 27.8 (±10.3) | 31.1 (±13.9) | .40 |
| Complications, n (%) | 3 (4.5) | 1 (3) | >.99 |
CTI = cavotricuspid isthmus; N-scar = control group; SCAR = scar group; SD = standard deviation.
Clinical outcomes
During a mean follow-up of 17 ± 11 months, the SCAR group experienced significantly higher rates of atrial arrhythmia recurrence (AF or AT) than the N-scar group. Kaplan-Meier survival analysis demonstrated that freedom from AF/AT at 12 months after the first procedure was 65.7% in the SCAR group compared with 82.9% in the N-scar group (Figure 1) (P = .005).
Weighted Cox proportional hazards analysis confirmed that an anterior scar was a significant independent predictor of arrhythmia recurrence (HR 4.1; 95% confidence interval 1.3–13; P = .015) (Figure 2). Other variables, including CHADS-VASc score, age, LA volume index, and ongoing AF duration, were not independently associated with recurrence after IPTW adjustment.
Figure 2.
Weighted Cox regression analysis with stepwise backward regression showing predictors of atrial arrhythmia (atrial fibrillation/atrial tachycardia) recurrence. AIC = Akaike information criterion; N-scar = control group; SCAR = scar group.
Discussion
Main findings
This study highlights the unfavorable impact of spontaneous anterior LA scar on arrhythmia-free survival after a standard ablation set (PVI, linear ablation including roof line, posterior mitral line with VOM-OH, and CTI line).
The major findings of the study are as follows:
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1.
LA anterior scar is associated with a specific patient phenotype.
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2.
Spontaneous LA anterior scarring is associated with a significantly lower arrhythmia-free survival rate at 12 months after the first procedure than patients without scar (65.7% vs 82.9%; P = .005). The presence of LA anterior scar is an independent predictor of arrhythmia recurrence, even after adjusting for confounders (HR 4.1; P = .015).
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3.
Additional ablation may be necessary for optimal outcomes in patients with anterior scarring.
Anterior atrial scar is associated with a specific patient phenotype
The higher prevalence of female sex and longer AF duration in the SCAR group suggests that these patients may represent a distinct phenotype of P-AF. Previous studies have shown that atrial fibrosis is more common in women, potentially owing to sex-specific differences in atrial remodeling and fibrosis pathways.7 Understanding the mechanisms underlying spontaneous anterior scarring could help identify high-risk patients earlier in the disease course.
An anterior scar is associated with a higher risk of arrhythmia recurrence after PV ablation and linear lesions
The arrhythmia-free survival rate without atrial scar observed in this study (82.9%) is consistent with previous reports on this ablation strategy.5 However, previous studies primarily focused on patients without significant atrial scarring, limiting their generalizability to patients with scar. Our findings expand on this knowledge by demonstrating that anterior scarring is a significant predictor of procedural failure.
The results of this study also align with previous studies linking low-voltage regions to increased arrhythmia recurrence.8 For example, Kottkamp et al9 reported that patients with low-voltage areas had higher recurrence rates after ablation, even when using extensive lesion sets.
A different ablation set may be necessary when facing an anterior scar
The findings of this study have clinical implications for the management of patients with P-AF and spontaneous anterior scar. The presence of an anterior scar appears to represent a unique substrate for arrhythmias that is not adequately addressed by the anatomic ablation set. 1 key element of the anatomic approach is the mitral line. A mitral line has the advantage of compartmentalizing the atrium and avoiding the occurrence of perimitral flutter. 2 types of mitral lines can be performed: anterior (from mitral annulus to right superior PV/left superior PV) or posterior (from mitral annulus to left inferior PV).
Therefore, a reasonable alternative could be represented by the anterior mitral line, which theoretically has the double advantage of preventing perimitral flutter and scar-related anterior AT.
The literature does not show uniform results concerning the choice of lines. 3 large-scale retrospective studies and 1 randomized controlled trial have addressed the efficacy of the anterior mitral line compared with the posterior mitral line.10, 11, 12, 13 A meta-analysis of these 4 studies (594 patients) found that, despite longer lines and later LA appendage activation, the anterior mitral line was associated with reduced AF/AT recurrence compared with the posterior line.14 Conversely, a study by Neira et al15 showed that the posterior line was associated with a long-term reduction in recurrent atrial arrhythmias driven by a reduction in macroreentrant atrial flutters compared with the anterior line. The outcomes associated with an anterior mitral line have been inconsistent when applied empirically to an unselected population of patients with AF.14 The MiLine study showed that an anterior mitral line in addition to PVI in patients with an anterior scar was associated with improved AF-/AT-free survival compared with standard treatment alone.16 However, the residual LA contraction in this population might be worsened.
Furthermore, the anterior mitral line is difficult to block by endocardial ablation. It may seem blocked with conventional maneuvers while epicardial conduction remains.17,18
Multiple studies have demonstrated the proarrhythmic potential of the VOM19 and the significant impact of adding VOM-OH in ablation of P-AF.5,20 The decision of including VOM-OH in the ablation strategy will also strongly influence the type of mitral line in favor of the posterior one.
According to the current literature, 25% of patients have low-voltage zones.6,21 2 ablation options can be discussed in the presence of an anterior scar: either change the ablation set to include a treatment of the scar or maintain the ablation set (PVI and linear lesions) with an individualized treatment of scar areas. Further studies are needed to evaluate these options.
Limitations
First, the retrospective design introduces the potential for selection bias and residual confounding, despite the use of IPTW. Second, the small sample size of the SCAR group limits the generalizability of the findings. It is because of the fact that, despite a long inclusion period, we have selected a large anterior scar, reflected by a mean scar surface area of 16 cm2. Third, the study only included patients treated with the PVI and linear ablation; thus, the results may not be applicable to other protocols. Finally, the follow-up period may be insufficient to capture late recurrences, which are known to occur in patients with P-AF.22
Future directions
Future studies should aim to:
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1.
Investigate whether incorporating targeted ablation within scarred regions improves outcomes in patients with an anterior scar.
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2.
Explore the mechanisms underlying spontaneous atrial scarring, particularly in women and patients with prolonged AF duration.
Conclusion
This study demonstrates that spontaneous anterior LA scar is associated with significantly lower arrhythmia-free survival after ablation using the Marshall-plan strategy. These findings underscore the need for additional or alternative ablation strategies to address the arrhythmogenic substrate in this patient population. Future research should focus on optimizing ablation techniques for patients with atrial scarring to improve long-term outcomes.
Disclosures
Drs Derval, Duchateau, Sacher, Jaïs, and Pambrun received modest consulting fees and speaking honoraria from Biosense Webster. Drs Sacher and Jaïs received modest speaking honoraria from Boston Scientific, Abbott, and Medtronic. All other authors have no relationship relevant to the contents of this paper to disclose.
Acknowledgments
The authors thank the medical team, researchers, and nurses without whom this work would not have been possible.
Funding Sources
This study was supported by a grant IHU Liryc ANR-10-IAHU-04.
Authorship
All authors attest they meet the current ICMJE criteria for authorship.
Patient Consent
All patients gave their written consent.
Ethics Statement
This study conforms to the guiding principles of the Declaration of Helsinki and has been approved by our Institutional Committee on Human Research.
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