Pacing cycle length-dependent electrophysiologic changes in left atrium: Poor validity of using low-voltage area and slow conduction area under specific pacing cycle length as absolute substrates of atrial fibrillation.

BACKGROUND: Pacing cycle length (PCL)-dependent changes in left atrial (LA) electrophysiologic properties have not been fully elucidated. OBJECTIVE: We aimed to elucidate these changes using a high-resolution mapping system. METHODS: Forty-eight patients underwent atrial fibrillation ablation with RHYTHMIA HDx. Paired LA maps under a baseline PCL (600 ms) and rapid PCL (300 ms) were acquired after pulmonary vein isolation under right atrial appendage pacing. The PCL-dependent change in the low-voltage area (LVA; area with <0.5 mV bipolar voltage), LA activation time (interval from first LA activation to wavefront collision at lateral wall), regional mean voltage, regional mean wave propagation velocity, and slow conduction area (area with <0.3 m/s wave propagation velocity) were quantitatively analyzed. RESULTS: Under the rapid PCL, the total LVA was significantly increased (7.6 ± 9.5 cm2 vs 6.7 ± 7.6 cm2; P = .031), especially in patients with a 10 cm2 LVA on the baseline PCL map (21.5 ± 9.1 cm2 vs 18.1 ± 6.5 cm2; P = .013). The LA activation time was also prolonged (87.9 ± 16.2 ms vs 84.0 ± 14.0 ms; P < .0001). Although the rapid PCL did not decrease the regional mean voltage, it significantly decreased the regional mean wave propagation velocity and increased the slow conduction area in all measured regions. CONCLUSION: LVA and slow conduction area can be emphasized by rapid PCL LA mapping. There may be poor validity in using these areas as absolute atrial fibrillation substrates without considering the PCL-dependent changes.

Follicle-stimulating hormone promotes atrial fibrosis in menopausal women with atrial fibrillation.

BACKGROUND: Postmenopausal women with atrial fibrillation (AF) exhibit a higher level of atrial fibrosis and a higher recurrence rate after ablation compared with men. However, the underlying mechanism remains unclear. OBJECTIVE: The purpost of this study was to investigate the mechanism through which menopause promotes atrial fibrosis. METHODS: In a prospective cohort of women with AF, regression analyses were conducted to assess the relationship between low-voltage area (LVA) and sex hormone levels. CREM-IbΔC-X mice, a spontaneous AF model, underwent bilateral ovariectomy (OVX). Electrocardiograms, echocardiograms, and Masson staining were performed. Follicle-stimulating hormone (FSH) stimulation was applied in male mice for 3 months. OVX was also applied in an angiotensin II (Ang II)-induced pressure overload mouse model, after programmed electrical stimulation and structural analyses. Bulk RNA sequencing (RNA-seq) was performed to elucidate potential mechanisms. RESULTS: Women demonstrated a significantly higher LVA burden than men (P < .001). A positive correlation was observed between LVA burden and FSH level (P = .002). Mice in the OVX group exhibited a significantly higher incidence of AF (P = .040) and atrial fibrosis (P = .021) compared with the Sham group, which could be attenuated by adeno-associated virus encoding small interfering RNA against Fshr. In male CREM-IbΔC-X mice, FSH stimulation promoted the occurrence of AF (P = .035) and atrial fibrosis (P = .002). In Ang II-induced female mice, OVX prompted atrial fibrosis, increased AF inducibility, and shortened atrial effective refractory period, which could be attenuated with knockdown of Fshr. RNA-seq indicated mitochondrial dysfunction. CONCLUSION: Postmenopausal women exhibited a higher LVA burden than men, which was positively correlated with FSH level. FSH promoted atrial fibrosis through oxidative stress.

Low-Voltage Area Ablation in Addition to Pulmonary Vein Isolation in Patients with Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Background: Low-voltage area (LVA) ablation, in addition to pulmonary vein isolation (PVI), has been proposed as a new strategy in patients with atrial fibrillation (AF), but clinical trials have shown conflicting results. We performed a systematic review and meta-analysis to assess the impact of LVA ablation in patient undergoing AF ablation (PROSPERO-registered CRD42024537696). Methods: Randomized clinical trials investigating the role of LVA ablation in addition to PVI in patients with AF were searched on PubMed, Embase, and the Cochrane Library from inception to 22 April 2024. Primary outcome was atrial arrhythmia recurrence after the first AF ablation procedure. Secondary endpoints included procedure time, fluoroscopy time, and procedure-related complication rate. Sensitivity analysis including only patients with LVA demonstration at mapping and multiple subgroups analyses were also performed. Results: 1547 patients from 7 studies were included. LVA ablation in addition to PVI reduced atrial arrhythmia recurrence (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.52-0.81, p < 0.001) with a number needed to treat to prevent recurrence of 10. No difference in procedure time (mean difference [MD] -5.32 min, 95% CI -19.01-8.46 min, p = 0.45), fluoroscopy time (MD -1.10 min, 95% CI -2.48-0.28 min, p = 0.12) and complication rate (OR 0.81, 95% CI 0.40-1.61, p = 0.54) was observed. Consistent results were demonstrated when considering only patients with LVA during mapping and in prespecified subgroups for AF type (paroxysmal vs. persistent), multicentric vs. monocentric trial, and ablation strategy in control group. Conclusions: In patients with AF, ablation of LVAs in addition to PVI reduces atrial arrhythmia recurrence without a significant increase in procedure time, fluoroscopy time, or complication rate.

An artificial intelligence-enabled electrocardiogram algorithm for the prediction of left atrial low-voltage areas in persistent atrial fibrillation.

OBJECTIVES: We aimed to construct an artificial intelligence-enabled electrocardiogram (ECG) algorithm that can accurately predict the presence of left atrial low-voltage areas (LVAs) in patients with persistent atrial fibrillation. METHODS: The study included 587 patients with persistent atrial fibrillation who underwent catheter ablation procedures between March 2012 and December 2023 and 942 scanned images of 12-lead ECGs obtained before the ablation procedures were performed. Artificial intelligence-based algorithms were used to construct models for predicting the presence of LVAs. The DR-FLASH and APPLE clinical scores for LVA prediction were calculated. We used a receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis to evaluate model performance. RESULTS: The data obtained from the participants were split into training (n = 469), validation (n = 58), and test sets (n = 60). LVAs were detected in 53.7% of all participants. Using ECG alone, the deep learning algorithm achieved an area under the ROC curve (AUROC) of 0.752, outperforming both the DR-FLASH score (AUROC = 0.610) and the APPLE score (AUROC = 0.510). The random forest classification model, which integrated a probabilistic deep learning model and clinical features, showed a maximum AUROC of 0.759. Moreover, the ECG-based deep learning algorithm for predicting extensive LVAs achieved an AUROC of 0.775, with a sensitivity of 0.816 and a specificity of 0.896. The random forest classification model for predicting extensive LVAs achieved an AUROC of 0.897, with a sensitivity of 0.862, and a specificity of 0.935. CONCLUSION: The deep learning model based exclusively on ECG data and the machine learning model that combined a probabilistic deep learning model and clinical features both predicted the presence of LVAs with a higher degree of accuracy than the DR-FLASH and the APPLE risk scores.

Left Atrial Electrophysiological Properties after Pulmonary Vein Isolation Predict the Recurrence of Atrial Fibrillation: A Cohort Study.

Background: The aim of this work was to investigate left atrial electrophysiological properties for their ability to predict the recurrence of atrial fibrillation (AF) following pulmonary vein isolation (PVI). Methods: The study comprised 53 patients with AF [62 (interquartile range (IQR): 52-68) years old; 47.2% females]. High-density, three-dimensional electro-anatomic mapping using PentaRay was conducted during sinus rhythm in the left atrium (LA) immediately after PVI. LA conduction time, conduction velocity in predefined anterior and posterior routes, low voltage area percentage and distribution were assessed. Results: The AF recurrence group had longer LA conduction time compared to the non-recurrence group [11 (IQR: 10-12) ms vs. 9 (IQR: 8-10) ms, p = 0.001). The percent low voltage area was greater in the recurrence group than the non-recurrence group [31.2 (IRQ: 7.1-49.3)% vs. 7.7 (IQR: 4.3-15.2)%, p = 0.008]. Multivariate Cox regression revealed that LA conduction time independently predicted AF recurrence following ablation over a median follow-up of 235 days [IQR: 154-382 days; hazard ratio (HR): 2.37, 95% confidence interval (CI): 1.08-5.23, p = 0.031]. The optimal cut-off for LA conduction time was 98 ms [area under curve (AUC): 0.926, sensitivity: 0.833, specificity: 0.894, p < 0.01]. Kaplan-Meier analysis revealed that patients with a conduction time > 98 ms had a higher rate of AF recurrence following ablation (p < 0.001). Conclusions: Patients with longer LA conduction time after PVI had more frequent AF recurrence.

Left atrial low voltage areas and heart failure in patients with atrial fibrillation: Implication of the atrial myopathy.

AIMS: Atrial fibrillation (AF) and heart failure (HF) affect each other and are often co-morbid. The fact that HF development is not uncommon even after ablation suggests that we need a deeper understanding of the pathology of these conditions. Atrial myocardial degeneration is an underlying factor in AF patients and may be associated with HF development after ablation. This study aimed to investigate the impact of low-voltage areas (LVAs) on HF prognosis after AF ablation. METHODS AND RESULTS: This observational study included 1481 consecutive patients undergoing initial ablation for AF. Left atrial LVAs were defined as regions with a bipolar peak-to-peak voltage of <0.50 mV. Patients were divided into three groups: no LVA (LVA size indexed to body surface area <3 cm2/m2, n = 1129), small LVA (3-10 cm2/m2, n = 217), and extensive LVA (≥10 cm2/m2, n = 135). A composite endpoint of HF hospitalization or death occurred more frequently in patients with larger LVAs (3.3% vs. 6.5% vs. 13.3%, P < 0.0001) during the 3-year follow up period. The extent of LVAs was independently related to the risk of the composite endpoint with an adjusted hazard ratio of 1.55 (95% confidence interval, 1.16-2.10) for each additional step of LVA classification (P = 0.003). CONCLUSIONS: LVA presence and its extent were associated with frequent HF hospitalization and death. Underlying atrial myopathy appears to define a poor HF prognosis after AF ablation.

Adjunctive low-voltage area ablation for patients with atrial fibrillation: An updated meta-analysis of randomized controlled trials.

BACKGROUND: The efficacy and safety of adjunctive low-voltage area (LVA) ablation on outcomes of catheter ablation (CA) for atrial fibrillation (AF) remains uncertain. METHODS: PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) comparing CA with versus without LVA ablation for patients with AF. Risk ratios (RR) with 95% confidence intervals (CI) were pooled with a random-effects model. Our primary endpoint was recurrence of atrial tachyarrhythmia (ATA), including AF, atrial flutter, or atrial tachycardia. We used R version 4.3.1 for all statistical analyses. RESULTS: Our meta-analysis included 10 RCTs encompassing 1780 patients, of whom 890 (50%) were randomized to LVA ablation. Adjunctive LVA ablation significantly reduced recurrence of ATA (RR 0.76; 95% CI 0.67-0.88; p < .01) and reduced the number of redo ablation procedures (RR 0.54; 95% CI 0.35-0.85; p < .01), as compared with conventional ablation. Among 691 (43%) patients with documented LVAs on baseline substrate mapping, adjunctive LVA ablation substantially reduced ATA recurrences (RR 0.57; 95% CI 0.38-0.86; p < .01). There was no significant difference between groups in terms of periprocedural adverse events (RR 0.78; 95% CI 0.39-1.56; p = .49). CONCLUSIONS: Adjunctive LVA ablation is an effective and safe strategy for reducing recurrences of ATA among patients who undergo CA for AF.

Atrial Functional Substrates for the Prediction of Atrial Fibrillation Recurrence After Pulmonary Vein Isolation.

Low-voltage areas have been used as atrial structural substrates in estimating fibrotic degeneration in patients with atrial fibrillation (AF). The high-resolution maps obtained by recently developed mapping catheters allow the visualization of several functional abnormalities. We investigated the association between left atrial (LA) functional abnormal findings on a high-resolution substrate map and AF recurrence in patients who underwent pulmonary vein isolation without any additional LA substrate ablation. This observational study included 100 consecutive patients who underwent second ablation for AF (paroxysmal, 48%; persistent, 52%). Patients with extra-pulmonary-vein LA substrate ablation during the initial and second ablation were excluded. LA mapping was performed using a 64-pole mini-basket catheter on the RHYTHMIA mapping system (Boston Scientific, Marlborough [Cambridge] Massachusetts). Patients were followed for 2 years. AF recurrence developed in 39 (39%) patients. On the high-resolution substrate map, AF recurrence was associated with the presence of the following findings: low-voltage areas (<1.0 mV, >5 cm2; hazard ratio [HR] = 2.53; 95% confidence interval [CI] = 1.30 to 4.93; p <0.006), fractionated-electrogram areas (≥5 peaks, >5 cm2; HR = 2.15, 95% CI = 1.10 to 4.19; p = 0.025), LA conduction time of >130 ms (HR = 3.11, 95% CI = 1.65 to 5.88, p <0.0001), deceleration zone (≥5 isochrones/cm2; HR = 1.97, 95% CI = 1.04 to 3.37, p = 0.039), and multiple septal break-out points (HR = 3.27, 95% CI = 1.50 to 7.16, p = 0.003). Accumulation of these risk factors increased AF recurrence in a stepwise manner, with an HR = 1.90, 95% CI = 1.44 to 2.52, p <0.00001 for each additional risk factor. In conclusion, a high-resolution map revealed new LA functional substrates associated with AF recurrence. Implementation of functional substrates may improve the prediction of AF recurrence after ablation, and possibly aid the development of tailored AF ablation strategies.

Sex difference in atrial scar prevalence: What can we learn from the STABLE-SR-III trial?

BACKGROUND: Female sex has long been recognized to present a higher risk of stroke and atrial fibrillation (AF) recurrence after circumferential pulmonary vein isolation (CPVI) than in males. However, the underlying mechanisms and benefits of additional low-voltage area (LVA) modification in women remain unknown. OBJECTIVE: The purpose of this study was to investigate differences in atrial substrate and efficacy of additive LVA ablation between sex subgroups. METHODS: Patients with paroxysmal atrial fibrillation (PAF) aged 65-80 years were randomly assigned to either CPVI plus LVA modification (STABLE-SR) group or CPVI alone group. The primary outcome was freedom from atrial arrhythmias after a single ablation procedure. RESULTS: Of 414 patients included in STABLE-SR-III, 204 (49.3%) were women (mean age 70.5 ± 4.7 years). Women demonstrated significantly higher LVA prevalence (51.5% vs 32.9%; P <.001) and LVA burden (6.5% vs 2.9%; P <.001) than men. In the STABLE-SR group, additional LVA ablation was associated with a 63% reduction in recurrence for women compared with the CPVI alone group (10.8% vs 29.4%; adjusted hazard ratio 0.37; 95% confidence interval 0.18-0.75; P for interaction = .040). However, this finding was not observed in men (18.7% vs 18.5%). In the female subgroup, both group 1 (CPVI + LVA modification) and group 3 (CPVI alone in females without LVA) had similar clinical outcomes, which were much better than in Group 2 (CPVI alone in women with LVA) (90% vs 83.8% vs 63.6%; P = .003). CONCLUSION: In older patients with PAF, women demonstrated more advanced atrial substrate, including higher prevalence and burden of LVA compared with men. Women may receive greater benefit from additional LVA modification than men.

Association between left atrial low-voltage area and induction and recurrence of macroreentrant atrial tachycardia in pulmonary vein isolation for atrial fibrillation.

BACKGROUND: The relationship between induction and recurrence due to atrial tachycardia (AT) and left atrial (LA) matrix progression after atrial fibrillation (AF) ablation remains unclear. METHODS: One hundred fifty-two consecutive patients with paroxysmal and persistent AF who underwent pulmonary vein isolation (PVI) and cavo-tricuspid isthmus (CTI) ablation and achieved sinus rhythm before the procedure were classified into three groups according to the AT pattern induced after the procedure: group N (non-induced), F (focal pattern), and M (macroreentrant pattern) in 3D mapping. RESULTS: The total rate of AT induction was 19.7% (30/152) in groups F (n = 13) and M (n = 17). Patients in group M were older than those in groups N and F, with higher CHADS2/CHA2DS2-VASc values, left atrial enlargement, and low-voltage area (LVA) size of LA. The receiver operating characteristic curve determined that the cut-off LVA for macroreentrant AT induction was 8.8 cm2 (area under the curve [AUC]: 0.86, 95% confidence interval [CI]: 0.75-0.97). The recurrence of AT at 36 months in group N was 4.1% (5/122), and at the second ablation, all patients had macroreentrant AT. Patients with AT recurrence in group N had a wide LVA at the first ablation, and the cut-off LVA for AT recurrence was 6.5 cm2 (AUC 0.94, 95%CI 0.88-0.99). Adjusted multivariate analysis showed that only LVA size was associated with the recurrence of macroreentrant AT (odds ratio 1.21, 95%CI 1.04-1.51). CONCLUSIONS: It is important to develop a therapeutic strategy based on the LVA size to suppress the recurrence of AT in these patients.

Ratio of P-Wave Duration to P-Wave Amplitude and Left Atrial Remodeling: Insights from Electrophysiological Findings and Myocardial Injury After Cryoballoon Ablation.

The impact of the P-wave morphology on clinical outcomes postcatheter ablation (post-CA) and recurrent arrhythmia characteristics or electrophysiologic findings in patients with paroxysmal atrial fibrillation (PAF) remains unclear. Patients with PAF who underwent cryoballoon ablation were enrolled. In 12-lead electrocardiography recorded within 1 month before CA, the P-wave duration (Pd) and P-wave vector magnitude (Pvm) (square root of the sum of the squared P-wave amplitude in leads II, V6, and one-half of the P-wave amplitude in V2) were measured and divided into 2 groups: patients with high and low Pd/Pvm based on a statistically calculated cut-off value. We evaluated the incidence of late recurrence of atrial fibrillation (LRAF), myocardial injury (high-sensitive troponin I), and the electrophysiologic findings in repeat ablation sessions. This study included 269 patients with PAF. The median follow-up duration was 697 days. The cut-off value of the Pd/Pvm for predicting LRAF was 740.7 ms/mV (area under the curve = 0.81, sensitivity = 58.2%, and specificity = 89.6%). Multivariable Cox proportional hazards analysis showed that high Pd/Pvm (>740.7 ms/mV) was significantly associated with LRAF (p <0.001). The high-sensitive troponin I level was significantly lower, and the ratio of DR-FLASH score >3 was significantly higher in those with high than low Pd/Pvm (p = 0.044 and p = 0.002, respectively). In the repeat ablation sessions, the Pd/Pvm in patients with atrial tachycardia-induced or spontaneously occurring during the repeat CA sessions was significantly higher than in those without (p = 0.009). There was a significant difference between the Pd/Pvm and low-voltage area (p <0.001). In conclusion, the Pd/Pvm is significantly associated with LRAF after cryoballoon ablation in patients with PAF and predicts left atrial low-voltage areas and atrial tachycardia inducibility.

Clinical impact of left atrial remodeling pattern in patients with atrial fibrillation: Comparison of volumetric, electrical, and combined remodeling.

INTRODUCTION: Atrial fibrillation (AF) is accompanied by various types of remodeling, including volumetric enlargement and histological degeneration. Electrical remodeling reportedly reflects histological degeneration. PURPOSE: To clarify the differences in determinants and clinical impacts among types of remodeling. METHODS: This observational study included 1118 consecutive patients undergoing initial ablation for AF. Patients were divided into four groups: minimal remodeling (left atrial volume index [LAVI] < mean value and no low-voltage area [LVA], n = 477); volumetric remodeling (LAVI ≥ mean value and no LVA, n = 361); electrical remodeling (LAVI < mean value and LVA presence, n = 96); and combined remodeling (LAVI ≥ mean value and LVA presence, n = 184). AF recurrence and other clinical outcomes were followed up for 2 and 5 years, respectively. RESULTS: Major determinants of each remodeling pattern were high age for electrical (odds ratio = 2.32, 95% confidence interval = 1.68-3.25) and combined remodeling (2.57, 1.88-3.49); female for electrical (3.85, 2.21-6.71) and combined remodeling (4.92, 2.90-8.25); persistent AF for combined remodeling (7.09, 3.75-13.4); and heart failure for volumetric (1.71, 1.51-2.53) and combined remodeling (2.21, 1.30-3.75). Recurrence rate after initial ablation increased in the order of minimal remodeling (20.1%), volumetric (27.4%) or electrical remodeling (36.5%), and combined remodeling (50.0%, p < .0001). A composite endpoint of heart failure, stroke, and death occurred in the order of minimal (3.4%), volumetric (7.5%) or electrical (8.3%), and combined remodeling (15.2%, p < .0001). CONCLUSION: Volumetric, electrical, and combined remodeling were each associated with a unique patient background, and defined rhythm and other clinical outcomes.

Prognostic impact of atrial cardiomyopathy: Long-term follow-up of patients with and without low-voltage areas following atrial fibrillation ablation.

BACKGROUND: Atrial cardiomyopathy is known as an underlying pathophysiological factor in the majority of patients with atrial fibrillation (AF). Left atrial low-voltage areas (LVAs) are reported to coincide with fibrosis and likely represent atrial cardiomyopathy. OBJECTIVE: The purpose of this study was to delineate differences in the long-term prognosis of patients stratified by the size of LVAs. METHODS: This observational study included 1488 consecutive patients undergoing initial ablation for AF. LVAs were defined as regions with a bipolar peak-to-peak voltage <0.50 mV. The total study population was divided into 3 groups stratified by LVA size: patients with no LVAs (n = 1136); those with small (<20 cm2) LVAs (n = 250) LVAs; and those with extensive (≥20 cm2) LVAs (n = 102). Composite endpoints of death, heart failure, and stroke were followed for up to 5 years. RESULTS: Composite endpoints developed in 105 of 1488 patients (7.1%), and AF recurrence occurred in 410 (27.6%). Composite endpoints developed more frequently in the order of patients with extensive LVAs (19.1%), small LVAs (10.8%), and no LVAs (5.1%) (P for trend <.0001). Multivariable analysis revealed that LVA presence was independently associated with higher incidence of composite endpoints, irrespective of AF recurrence (modified hazard ratio 1.73; 95% confidence interval 1.13-2.64; P = .011) CONCLUSION: LVA presence and its extent both were associated with poor long-term composite endpoints of death, heart failure, and stroke, irrespective of AF recurrence or other confounders. Underlying atrial cardiomyopathy seems to define a poor prognosis after AF ablation.

Association between P-wave terminal force in lead V1 and extent of left atrial low-voltage substrate in older patients with paroxysmal atrial fibrillation.

BACKGROUND: The P-wave terminal force in lead V1 (PTFV1) is a marker of cardiomyopathy and risk of atrial fibrillation (AF). Low-voltage area (LVA) in the left atrium (LA), which indicates underlying atrial fibrosis, could predict AF recurrence. This study aimed to investigate the correlation between PTFV1 and LVA in older patients with paroxysmal AF. METHODS: From May 1, 2020, to October 31, 2021, a total of 162 patients aged 65-80 years with paroxysmal AF who underwent index ablation procedures were enrolled. PTFV1 was measured in sinus rhythm (SR) using 12-lead electrocardiograms prior to the ablation. Abnormal PTFV1 was defined as a ≥ 4 mVms depression. Additional LVA ablation beyond circumferential pulmonary vein isolation (CPVI) was performed if LVAs were found. RESULTS: Among the 162 patients, 88 had a normal PTFV1 and 74 had an abnormal PTFV1 prior to ablation. There was a significant difference in LVA in patients with and without an abnormal PTFV1 (LVA, 11.0 vs. 5.1 cm2, P < 0.001; LVA burden, 8.9% vs. 4.5%, P < 0.001). PTFV1 and PTAV1 were highest in the upper tertile with extensive LVAs (P < 0.001). Multivariate analysis revealed that abnormal PTFV1 was an independent predictor of LVAs (ß = 4.961; 95% CI, 2.135-7.788; P < 0.001). After a median follow-up of 23 months, the AF-free survival rate was similar between the normal PTFV1 group and the abnormal PTFV1 group (13/88 vs. 12/74, hazard ratio [HR], 0.933 [95% CI, 0.425-2.047]; P = 0.861). CONCLUSIONS: Abnormal PTFV1 at baseline was independently associated with the extent of LVA in older patients with paroxysmal AF.

Recurrence as isthmus-related atrial tachycardia: A cautionary point of low-voltage area homogenization of persistent atrial fibrillation.

A 66-year-old female underwent persistent atrial fibrillation ablation. After pulmonary vein isolation and homogenization of low-voltage areas (LVAs), atrial tachycardia (AT) was not induced at the first session; however, it recurred one year after the procedure. During the second session, the extensive LVAs were distributed in the same area of the left atrial anterior wall and expanded possibly due to the previous LVA homogenization. The activation map revealed a macroreentrant AT circuit with the critical isthmus between the isolated right superior pulmonary vein and homogenized LVAs. Although the Ripple map algorithm failed to visualize dynamic bars, extremely low voltage and fractionated potentials (amplitude, 0.04 mV) were observed at the isthmus. Currently, there are various procedural endpoints of LVA-guided ablation (e.g. local electrogram reduction > 50 % or <0.1 mV in amplitude). In this case, incomplete transmural lesions may have led to slow conduction, which could have become an AT substrate. In cases with extensive LVAs on the left atrial anterior wall, eliminating any potential channels may be important for preventing future iatrogenic ATs. LVA-guided ablation should be performed on an individual basis, considering the potential benefits and harms based on the extent and location of LVAs. Learning objective: Currently, the procedural endpoint of low-voltage area (LVA)-guided ablation varies across studies. Because any low-voltage potentials, except scars, can cause slow conduction, LVA-guided ablation with an endpoint of local electrogram voltage reduction can unintentionally generate an iatrogenic slow conduction isthmus. LVA-guided ablation should be individually performed, considering the potential benefits and harms based on the extent and location of LVAs.

Impact of Posterior Left Atrial Voltage on Ablation Outcomes in Persistent Atrial Fibrillation: CAPLA Substudy.

BACKGROUND: Pulmonary vein isolation (PVI) is less effective in patients with persistent atrial fibrillation (PsAF). Adjunctive ablation targeting low voltage areas (LVAs) may improve arrhythmia outcomes. OBJECTIVES: This study aims to compare the outcomes of adding posterior wall isolation (PWI) to PVI, vs PVI alone in PsAF patients with posterior wall LVAs. METHODS: The CAPLA (Effect of Catheter Ablation Using Pulmonary Vein Isolation With vs Without Posterior Left Atrial Wall Isolation on Atrial Arrhythmia Recurrence in Patients With Persistent Atrial Fibrillation) study was a multicenter, randomized trial involving PsAF patients randomized 1:1 to either PVI alone or PVI with PWI. Voltage mapping performed during pacing pre-ablation was reviewed offline, with LVA defined as bipolar voltage of <0.5 mV. The primary endpoint was freedom from any documented atrial arrhythmia of >30 seconds off antiarrhythmic medication at 12 months after a single ablation procedure in patients with posterior LVA. RESULTS: A total of 210 patients (average 64.6 ± 9.2 years,73.3% males, median atrial fibrillation duration 4.5 months [IQR: 2 to 8 months]) underwent multipolar left atrial mapping during coronary sinus pacing with posterior LVA present in 69 (32.9%). Patients with posterior LVA were more likely to have LVA in other atrial regions (91.7% vs 57.1%; P < 0.01), larger left atrial diameter (4.8 cm vs 4.4 cm; P < 0.01), and significantly increased risk of atrial arrhythmia recurrence at 12 months (LVA: 56.5% vs no LVA: 41.4%; HR: 1.51; 95% CI: 1.01-2.27; P = 0.04) compared to no posterior LVA. However, the addition of PWI to PVI did not significantly improve freedom from atrial arrhythmia recurrence over PVI alone (PVI with PWI: 44.8% vs PVI: 41.9%; HR: 0.95; 95% CI: 0.51-1.79; P = 0.95). CONCLUSIONS: In patients with PsAF undergoing catheter ablation, posterior LVA was associated with a significant increase in atrial arrhythmia recurrence. However, the addition of PWI in those with posterior LVA did not reduce atrial arrhythmia recurrence over PVI alone.

Comparing Left Atrial Low Voltage Areas in Sinus Rhythm and Atrial Fibrillation Using Novel Automated Voltage Analysis: A Pilot Study.

Background: Low voltage areas (LVAs) have been proposed as surrogate markers for left atrial (LA) scar. Correlation between voltages in sinus rhythm (SR) and atrial fibrillation (AF) have previously been measured via point-by-point analysis. We sought to compare LA voltage composition measured in SR to AF, utilizing a high-density automated voltage histogram analysis (VHA) tool in those undergoing pulmonary vein isolation (PVI) for persistent AF (PeAF). Methods: We retrospectively analyzed patients with PeAF undergoing de novo PVI. Maps required ≥ 1,000 voltage points in each rhythm and had a standardized procedure (mapped in AF then remapped in SR post-PVI). We created six anatomical segments (AS) from each map: anterior, posterior, roof, floor, septal and lateral AS. These were analyzed by VHA, categorizing atrial LVAs into 10 voltage aliquots 0 - 0.5 mV. Data were analyzed using SPSS v.26. Results: We acquired 58,342 voltage points (n = 10 patients, mean age: 67 ± 13 years, three females). LVA burdens of ≤ 0.2 mV, designated as "severe LVAs", were comparable between most AS (except on the posterior wall) with good correlation. Mapped voltages between the ranges of 0.21 and 0.5 mV were labeled as "diseased LA tissue", and these were found significantly more in AF than SR. Significant differences were seen on the roof, anterior, posterior, and lateral AS. Conclusions: Diseased LA tissue (0.21 - 0.5 mV) burden is significantly higher in AF than SR, mainly in the anterior, roof, lateral, and posterior wall. LA "severe LVA" (≤ 0.2 mV) burden is comparable in both rhythms, except with respect to the posterior wall. Our findings suggest that mapping rhythm has less effect on the LA with voltages < 0.2 mV than 0.2 - 0.5 mV across all anatomical regions, excluding the posterior wall.

Baseline left atrial low-voltage area predicts recurrence after pulmonary vein isolation: WAVE-MAP AF results.

AIMS: Electro-anatomical mapping may be critical to identify atrial fibrillation (AF) subjects who require substrate modification beyond pulmonary vein isolation (PVI). The objective was to determine correlations between pre-ablation mapping characteristics and 12-month outcomes after a single PVI-only catheter ablation of AF. METHODS AND RESULTS: This study enrolled paroxysmal AF (PAF), early persistent AF (PsAF; 7 days-3 months), and non-early PsAF (>3-12 months) subjects undergoing de novo PVI-only radiofrequency catheter ablation. Sinus rhythm (SR) and AF voltage maps were created with the Advisor HD Grid™ Mapping Catheter, Sensor Enabled™ for each subject, and the presence of low-voltage area (LVA) (low-voltage cutoffs: 0.1-1.5 mV) was investigated. Follow-up visits were at 3, 6, and 12 months, with a 24-h Holter monitor at 12 months. A Cox proportional hazards model identified associations between mapping data and 12-month recurrence after a single PVI procedure. The study enrolled 300 subjects (113 PAF, 86 early PsAF, and 101 non-early PsAF) at 18 centres. At 12 months, 75.5% of subjects were free from AF/atrial flutter (AFL)/atrial tachycardia (AT) recurrence. Univariate analysis found that arrhythmia recurrence did not correlate with AF diagnosis, but LVA was significantly correlated. Low-voltage area (<0.5 mV) >28% of the left atrium in SR [hazard ratio (HR): 4.82, 95% confidence interval (CI): 2.08-11.18; P = 0.0003] and >72% in AF (HR: 5.66, 95% CI: 2.34-13.69; P = 0.0001) was associated with a higher risk of AF/AFL/AT recurrence at 12 months. CONCLUSION: Larger extension of LVA was associated with an increased risk of arrhythmia recurrence. These subjects may benefit from substrate modification beyond PVI.