Atrial Substrate Research Articles

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

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. From May 1, 2020, to October 31, 2021, a total of 162 patients aged 65-80years 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. 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 (β = 4.961; 95% CI, 2.135-7.788; P < 0.001). After a median follow-up of 23months, 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). Abnormal PTFV1 at baseline was independently associated with the extent of LVA in older patients with paroxysmal AF.

Echocardiography and Electrocardiography in Detecting Atrial Cardiomyopathy: A Promising Path to Predicting Cardioembolic Strokes and Atrial Fibrillation

(1) Background: Atrial cardiomyopathy constitutes an intrinsically prothrombotic atrial substrate that may promote atrial fibrillation and thromboembolic events, especially stroke, independently of the arrhythmia. Atrial reservoir strain is the echocardiography marker with the most robust evidence supporting its prognostic utility. The main aim of this study is to identify atrial cardiomyopathy by investigating the association between left atrial dysfunction in echocardiography and P-wave abnormalities in the surface electrocardiogram. (2) Methods: This is a community-based, multicenter, prospective cohort study. A randomized sample of 100 patients at a high risk of developing atrial fibrillation were evaluated using diverse echocardiography imaging techniques, and a standard electrocardiogram. (3) Results: Significant left atrial dysfunction, expressed by a left atrial reservoir strain &lt; 26%, showed a relationship with the dilation of the left atrium (p &lt; 0.001), the left atrial ejection fraction &lt; 50% (p &lt; 0.001), the presence of advanced interatrial block (p = 0.032), P-wave voltage in lead I &lt; 0.1 mV (p = 0.008), and MVP ECG score (p = 0.036). (4) Conclusions: A significant relationship was observed between left atrial dysfunction and the presence of left atrial enlargement and other electrocardiography markers; all of them are non-invasive biomarkers of atrial cardiomyopathy.

Standardized 2D atrial mapping and its clinical applications

The visualization and comparison of electrophysiological information in the atrium among different patients could be facilitated by a standardized 2D atrial mapping. However, due to the complexity of the atrial anatomy, unfolding the 3D geometry into a 2D atrial mapping is challenging. In this study, we aim to develop a standardized approach to achieve a 2D atrial mapping that connects the left and right atria, while maintaining fixed positions and sizes of atrial segments across individuals. Atrial segmentation is a prerequisite for the process. Segmentation includes 19 different segments with 12 segments from the left atrium, 5 segments from the right atrium, and two segments for the atrial septum. To ensure consistent and physiologically meaningful segment connections, an automated procedure is applied to open up the atrial surfaces and project the 3D information into 2D. The corresponding 2D atrial mapping can then be utilized to visualize different electrophysiological information of a patient, such as activation time patterns or phase maps. This can in turn provide useful information for guiding catheter ablation. The proposed standardized 2D maps can also be used to compare more easily structural information like fibrosis distribution with rotor presence and location. We show several examples of visualization of different electrophysiological properties for both healthy subjects and patients affected by atrial fibrillation. These examples show that the proposed maps provide an easy way to visualize and interpret intra-subject information and perform inter-subject comparison, which may provide a reference framework for the analysis of the atrial fibrillation substrate before treatment, and during a catheter ablation procedure.

Impact of Low Voltage Threshold Adjustment on Activation Mapping Interpretation for Atrial Tachycardia in Low-Voltage Left Atrium.

The misinterpretation of activation propagation within low voltage zone (LVZ) can complicate atrial tachycardia (AT) mechanism analysis, especially in patients with remodeled atrial substrate. This study investigated the impact of low voltage threshold adjustment (LVTA) on left atrial (LA) tachycardia activation mapping interpretation. We identified 55 ATs in 42 patients undergoing catheter ablation for LA tachycardia, with a mean LA voltage of 0.5 mV. Activation mapping of LA or both atria was used to evaluate AT mechanisms before and after LVTA. Patients underwent regular clinic follow-up after the procedure. Comparing activation mapping before and after LVTA revealed four categories: (1) complete change in AT circuit and ablation design in 9 ATs; (2) an unchanged AT circuit but tailored ablation design in 16 ATs; (3) identification of bystander gaps in 3 ATs; (4) an unchanged AT circuit and ablation design in 27 ATs. Effective ablation, defined as AT termination or circuit change, was obtained in all 9 Type 1 ATs and 15 of 16 Type 2 ATs by targeting the critical area identified by activation mapping after LVTA. After a median follow-up of 16.5 months, the cumulative freedom from AT was 69.3%. In patients with low LA voltage, conduction propagation hidden within LVZ was not uncommon, but is often excluded from activation mapping. LVTA can uncover this subtle conduction propagation with reliable accuracy, improving the veracity of activation mapping, and helping guide subsequent ablation.

Cryoballoon ablation of non-PV triggers in persistent atrial fibrillation.

Cryoballoon-based catheter ablation has emerged as an efficacious and safe therapeutic intervention for patients with paroxysmal atrial fibrillation (PAF). PAF is primarily associated with the triggers in the pulmonary vein (PV). However, persistent atrial fibrillation (PeAF) is a complex condition that involves changes in the atrial substrate and the presence of non-PV triggers. Therefore, a comprehensive treatment approach is necessary for patients with PeAF. Utilizing a 3D electroanatomical map, the radiofrequency-based ablation technique adeptly identifies and targets the atrial substrate and non-PV triggers. On the other hand, the cryoballoon-based AF ablation was initially designed for PV isolation. However, its single-shot feature makes it a great choice for electrophysiologists looking to address non-PV triggers. It is possible to target the left atrial appendage (LAA), superior vena cava (SVC), left atrial roof, and posterior wall using the apparatus's unique configuration and ablation abilities. This review focuses on the increasing literature regarding cryoballoon-based methods for non-PV trigger ablation. Specifically, it delves into the technical procedures used to isolate the LAA, SVC, and ablate the left atrial roof and posterior wall.

Duration of left and right atrial activation wavefront assessed non-invasively is significantly higher in patients with atrial fibrillation than in controls

Abstract Introduction Ablation strategies in atrial fibrillation (AF) are currently a "one-size- fits- all" type of approach. Pulmonary vein isolation as the standard of care is not perfect, especially in the persistent forms, but none of the alternatives has shown better results. The dichotomic paroxysmal versus persistent AF classification in no longer acceptable. Characterization of the atrial substrate before ablation is needed. Electrocardiographic imaging (ECGI) is capable of non-invasively assess atrial activation in a single beat and in a panoramic fashion. The aim of this study was to evaluate the feasibility and accuracy of ECGI to assess the activation speed and identify possible targets for ablation. Methods We studied 18 consecutive patients, 9 referred for ablation of paroxysmal AF and 9 without AF, referred for ablation of premature ventricular contractions (PVCs), that had an ECGI performed before ablation. No patient had structural heart disease and all patients had normal electrocardiographic evaluation in sinus rhythm (SR). The ECGI was performed in SR with the AMYCARD 01 system, based on body surface electrocardiograms of a maximum of 224 electrodes and computed tomography imaging data. Total duration of atrial activation, left atrial (LA), and right atrial (RA) activation duration, and presence of lines of conduction block (LOB) defined as the presence of a jump in the local activation time of 50 ms or more between contiguous points, were assessed. The results were compared in patients with and without AF. Results The results are depicted in the Table. Patients with AF were older. Total atrial activation duration, LA, and RA activation duration were longer in patients with AF and there was a trend towards a higher prevalence of LOB in the LA in patients with AF (Figure). Discussion &amp; Conclusion Total atrial activation duration as well as LA and RA activation duration assessed with the ECGI were significantly prolonged in patients with AF. Presence of LOB in the LA showed a trend towards a higher prevalence in AF patients. These pilot study has proved that this technology is accurate in identifying a pathological substrate in AF patients. We intend to use ECGI in a subsequent study that will include patients with AF both in paroxysmal and persistent forms, in order to identify markers of disease as well as possible targets to perform a customized AF ablation.Comparison between AF and control groupsECGI showing local activation times

Left atrial fibrosis-guided ablation in patients with atrial fibrillation: a systematic review and meta-analysis of randomized trials

Abstract Background Left atrial fibrosis is related to atrial fibrillation (AF) recurrence after AF ablation. However, the benefit of patient-specific substrate modification guided by fibrosis delineated on voltage mapping or magnetic resonance imaging (MRI) is conflicting. Objective To compare the efficacy and safety of additional modification of left atrial fibrosis [identified by low-voltage area (LVA) or late gadolinium-enhancement on MRI] vs. circumferential pulmonary vein isolation (PVI) with or without stepwise ablation not targeting fibrosis in AF. Methods A systematic search of PubMed, EMBASE, and Cochrane Central Register of Controlled Trials was performed from inception to November 2022. Only randomized studies investigating the utility of fibrosis-guided substrate modification beyond conventional PVI were included. The primary outcome was a recurrence of any atrial arrhythmia. Major adverse events and procedural, fluoroscopic, and total ablation time were defined as secondary outcomes. We calculated pooled estimates of the outcomes by a random-effect model and reported them as risk ratio (RRs) and 95% confidence interval (CI). Results A total of 9 studies (8 randomized controlled clinical trials and 1 randomized design within a prospective study) and 2135 patients with AF were included. The atrial arrhythmia recurrence was lower in the additional fibrosis-guided ablation group (RR 0.82; 95% CI 0.71-0.94; p=0.006) (Figure 1A). No differences were found between fibrosis-guided substrate modification and conventional PVI group in major adverse events [RR 1.25 (0.55-2.81), p=0.598)] and mean differences of procedural time [-2.88 (-40.34 to 34.57) min], fluoroscopic time [1.82 (-1.86 to 5.49) min], and total ablation time [-14.28 (-48.70 to 20.14) min]. In the stratified analyses, there were no interactions of the lower atrial arrhythmia recurrences within the modality of fibrosis identification (LVA vs. delayed enhancement on MRI), type of AF (paroxysmal vs. persistent), the burden of LVA (no or low vs. high), and strategy of the control group (PVI only vs. PVI plus stepwise ablation) (Figure 1B). Conclusion By incorporating two modalities of left atrial substrate evaluation – voltage mapping and MRI – we conclude that the individually tailored fibrosis-guided ablation in AF is associated with a lower recurrence after catheter ablation.

Abstract 14862: Electrophysiological Predictors of Susceptible Atrial Substrate for the Onset and Recurrence of Atrial Fibrillation

Introduction: Atrial electro-anatomical substrate is essential for pathogenesis of atrial fibrillation (AF). Electrophysiological markers of AF susceptibility, however, are not well characterized. Identifying markers of atrial substrate has significant clinical implications in early detection and intervention for AF or stratifying patients at higher risk of AF recurrence following ablation. Hypothesis: We hypothesized that conduction indices on surface electrocardiogram (ECG) and intracardiac electrogram (EGM) may predict susceptibility and/or AF recurrence following ablation. Methods: We studied all consecutive patients who underwent electrophysiological study and catheter ablation for AF or atrioventricular nodal reentrant tachycardia (AVNRT) from 2013 to 2018. Atrial conduction indices were measured on ECG and EGM during the electrophysiology study. We evaluated correlations between both AF and AF recurrence with conduction indices, and associations between AF recurrence and conduction indices were evaluated with univariate logistic regression analyses and machine learning. Results: The study population included 387 patients with AF (mean age 63 years, 31% female) and compared to patients with AVNRT (n=94) who were considered as a control group. AF was associated with significant prolongation of all measured surface ECG and EGM parameters (p&lt;0.05). During a mean follow up of 5±2 years, recurrence of AF (48%) after successful ablation occurred in patient with longer P wave duration, left atrial (LA) conduction duration, proximal to distal coronary sinus (pCS-dCS) interval, and P-dCS interval (p&lt;0.05). Prolonged P wave duration, LA duration, pCS-dCS interval, and QRS duration were predictors of AF recurrence. Machine learning modeling determined that pCS-dCS interval, QRS duration, and LA duration (lead V1 and II) were the most impactful conduction indices for AF recurrence. Conclusions: Atrial conduction indices are markers of susceptible substrate for the onset and the recurrence of AF after successful ablation. LA conduction parameters can be used for risk stratification to facilitate early detection and management of AF.

Abstract 18225: Left Atrial Volume Index and Outcomes in Paroxysmal Atrial Fibrillation (pAF) in the Real-AF Registry

Introduction: Catheter ablation via pulmonary vein isolation Is one of the most commonly performed procedures for treating paroxysmal atrial fibrillation (pAF). Left atrium size affects ablation strategies and outcomes in patients with pAF. We analyzed the left atrium index (LAi) to determine associations with recurrent arrhythmias at 12 months post-ablation and the ablation strategies used. Methods: The Real-world Experience of Catheter Ablation for the Treatment of Symptomatic Paroxysmal (pAF) and Persistent (PsAF) Atrial Fibrillation registry (Real-AF) is a multicenter prospective registry that is enrolling patients undergoing AF ablation at high-volume centers. Left atrial volume was reconstructed using CARTO 3D. LAi was separated into normal range: &lt; 34 ml/m2, mildly enlarged 35 - 41 ml/m2, moderately enlarged 42 - 48 ml/m2, and severely enlarged &gt; 49 ml/m2 based on the American Society of Echocardiogram guidelines. Ablation strategies were divided into pulmonary vein isolation (PVI) alone or PVI+ ablation, including PVI and additional atrial arrhythmogenic substrates. Recurrence of arrhythmias at 12 months post-ablation and ablation strategies were compared. Results: A total of 1824 were included. In patients with pAF 12.2% developed recurrent arrhythmia at 12 months. When compared to normal LAi, patients with pAF with moderately and severely enlarged LAi were more likely to have a recurrence of arrhythmias at 12 months (Table 1). Women with pAF and moderately and severely enlarged LAi were more likely to have recurrence of arrhythmias (Table 1). A total of 1433 underwent PVI only ablations, and 391 underwent PVI+ ablations. Abnormal LAi was also associated with patients undergoing PVI+ ablations compared to PVI only ablations (Table 1). Conclusions: In patients with pAF and abnormal LA size was associated with more recurrent arrhythmias at 12 months post-ablation. Patients with enlarged LAi were more likely to have PVI+ ablations.

Abstract 13928: Targeted Atrial Inhibition of Galphaq Signaling With Inhibitory Peptides Attenuates Fibrosis and Inducibility of Atrial Fibrillation in a Canine Heart Failure Model

Introduction: Endothelial dysfunction, a hallmark of heart failure (HF), is closely associated with atrial fibrillation (AF). However, the precise role of endothelial dysfunction in creating an atrial arrhythmogenic substrate is unknown. Endothelin-1 (ET-1) and its downstream Gα q signaling are significantly upregulated in the atria of patients with HF. We therefore hypothesized that ET-1-Gα q signaling contributes to adverse structural remodeling in the atria in the setting of HF. Hypothesis: Inhibition of atrial ET-1-Gα q signaling with Gα q inhibitory peptides (Gα q -ct) will attenuate the development of atrial fibrosis and AF inducibility in a HF model. Methods: Plasmids expressing Gα q -ct were injected and electroporated in the left atria of 4 dogs. LacZ or scrambled plasmids were used in 8 control dogs. HF was induced by ventricular tachypacing (VTP) at 240 bpm for 3 weeks. At terminal EP study, left atrial conduction vectors were recorded with high-density mapping and AF inducibility assessed. Left atrial fibrosis was quantified by Masson Trichrome. Results: All animals developed clinical HF (prolonged capillary refill time, ascites, reduced activity level) and LV systolic dysfunction by echocardiogram (LVEF 17.5±8.3% in Gα q -ct, 13.7±3.1% in controls, p=0.55). Conduction inhomogeneity was reduced in Gα q -ct animals (example of posterior left atrium recordings in Fig. A). AF was less inducible in Gα q -ct than control animals (4.8% of pacing attempts Vs 17.8%, p&lt;0.001, Fig. B) and AF episodes were shorter (5.6±0.9 sec Vs 63.8±11.9 sec). Left atrial fibrosis was significantly attenuated in Gα q -ct animals Vs controls (Fig. C). Conclusions: Gα q signaling contributes to atrial fibrosis and subsequent AF susceptibility in VTP-induced HF, thereby highlighting an important role for ET-1 signaling in HF-related atrial remodeling. Future optimization of gene therapy targeting ET-1 signaling may lead to novel, mechanism-guided treatments for AF in the context of HF.

Comparison of pulsed-field ablation versus very high power short duration-ablation for pulmonary vein isolation.

The newly introduced nonthermal pulsed field ablation (PFA) is a promising technology to achieve fast pulmonary vein isolation (PVI) with high acute success rates and good safety features. However, previous studies have shown that very high power short duration ablation (VHPSD) is also highly effective and fast to achieve PVI with potentially less arrhythmia recurrence compared to conventional radiofrequency ablation. Data comparing PFA to VHPSD-PVI is lacking. This study compared procedural and outcome data for PFA-PVI to VHPSD-PVI in patients with paroxysmal or persistent atrial fibrillation (PAF/persAF). Consecutive patients undergoing de novo PVI (PFA or VHPSD) were included in this analysis. For PFA-PVI a pentaspline 20 electrode catheter was used. For VHPSD-PVI an enhanced irrigated catheter with a power setting of 70 W/7 s (70 W/5 s at posterior wall) was employed in conjunction with electro-anatomical mapping. All procedures were performed in deep analgo-sedation. A total of n = 114 patients (n = 57[50%] PFA, n = 17[30%] PAF; n = 40[70%] persAF) were included in this analysis. PVI was successful in all patients. The PFA group revealed a significantly shorter procedure duration (65 ± 17 min vs. 95 ± 23 min, p < 0.01) but longer fluoroscopy time (PFA 15 ± 5 min and VHPSD 12 ± 3 min; p < 0.001). At follow-up after median 125 days (interquartile range: 109-162) n = 46 PFA (80.7%) and n = 44 VHPSD pts (77.2%) were free from atrial arrhythmia after a single procedure (p = 0.819). Two tamponades occurred in the PFA while in VHPSD two pts suffered groin bleedings. One clinically nonsignificant PV stenosis occurred in the VHPSD group. Pulsed-field ablation and VHPSD-PVI seem to be highly effective and safe to achieve PVI in the setting of PAF and persAF with comparable arrhythmia-free survival. However, procedure duration for PFA PVI is significantly shorter and therefore may be of potential benefit. Compared to PFA VHPSD-PVI might ensure information on left atrial substrate allowing to target concomitant secondary tachycardias.

Obstructive sleep apnea in the patient with atrial fibrillation: current knowledge and remaining uncertainties.

Obstructive sleep apnea (OSA) is highly prevalent in patients with atrial fibrillation and plays a causal role for OSA in the pathogenesis of atrial fibrillation. The presence of OSA in atrial fibrillation is associated with increased symptom burden and increased risk of hospitalizations. Furthermore, untreated OSA is associated with an increased risk of atrial fibrillation recurrence post ablation or cardioversion, and observational studies suggest that continuous positive airway pressure (CPAP) therapy can attenuate this risk. This review describes our current understanding of the relationship between OSA and atrial fibrillation with an emphasis on emerging evidence. Recent studies have identified novel screening questionnaires, which may be superior to traditional questionnaires in identifying OSA in atrial fibrillation populations. Significant night-to-night variability in OSA severity has been shown in atrial fibrillation patients, which has implications for diagnostic testing. While several small, randomized control trials (RCTs) have not shown CPAP therapy to be effective in reducing atrial fibrillation burden, one RCT did show CPAP can attenuate the atrial substrate with implications for long-term outcomes. Further RCTs, appropriately powered, and focused on well defined cohorts, are required to guide management decisions regarding screening and treatment of OSA in atrial fibrillation populations.

Impact of gender on left atrial low-voltage zones in patients with persistent atrial fibrillation: results of a voltage-guided ablation.

Gender-related differences have been reported in atrial fibrotic remodeling and prognosis of atrial fibrillation (AF) patients after ablation. We assessed in persistent AF the regional distribution of left atrial (LA) bipolar voltage and the extent of low-voltage zones (LVZ) according to gender as well as the results of a voltage-guided substrate ablation. Consecutive patients who underwent a voltage-guided AF ablation were enrolled. LA endocardial voltage maps were obtained using a 3D electro-anatomical mapping system in sinus rhythm. LVZ was defined as <0.5 mV. A total of 115 patients were enrolled (74 men, 41 women). The LA bipolar voltage amplitude was twice lower in the whole LA (p < 0.01) and in each atrial region in women compared with men, whereas the LA indexed volume was similar. LVZ were found in 56.1% of women and 16.2% of men (p < 0.01). LVZ were also more extensive in women (p = 0.01), especially in the anterior LA. Atrial voltage alteration occurred earlier in women than in men. In a multivariate analysis, the female sex (OR 12.99; 95% CI, 3.23-51.63, p = 0.0001) and LA indexed volume (OR 1.09; 95% CI, 1.04-1.16, p = 0.001) were predictive of LVZ. Atrial arrhythmia-free survival was similar in men and women 36 months after a single ablation procedure. The study reports a strong relationship between the female gender and atrial substrate remodeling. The female gender was significantly associated with higher incidence, earlier occurrence, and greater extent of LVZ compared with men. Despite the female-specific characteristics in atrial remodeling, LVZ-guided ablation may improve the AF ablation outcome in women.

High-density mapping of the average complex interval helps localizing atrial fibrillation drivers and predicts catheter ablation outcomes.

Persistent Atrial Fibrillation (PersAF) electrogram-based ablation is complex, and appropriate identification of atrial substrate is critical. Little is known regarding the value of the Average Complex Interval (ACI) feature for PersAF ablation. Using the evolution of AF complexity by sequentially computing AF dominant frequency (DF) along the ablation procedure, we sought to evaluate the value of ACI for discriminating active drivers (AD) from bystander zones (BZ), for predicting AF termination during ablation, and for predicting AF recurrence during follow-up. We included PersAF patients undergoing radiofrequency catheter ablation by pulmonary vein isolation and ablation of atrial substrate identified by Spatiotemporal Dispersion or Complex Fractionated Atrial Electrograms (>70% of recording). Operators were blinded to ACI measurement which was sought for each documented atrial substrate area. AF DF was measured by Independent Component Analysis on 1-minute 12-lead ECGs at baseline and after ablation of each atrial zone. AD were differentiated from BZ either by a significant decrease in DF (>10%), or by AF termination. Arrhythmia recurrence was monitored during follow-up. We analyzed 159 atrial areas (129 treated by radiofrequency during AF) in 29 patients. ACI was shorter in AD than BZ (76.4 ± 13.6 vs. 86.6 ± 20.3 ms; p = 0.0055), and mean ACI of all substrate zones was shorter in patients for whom radiofrequency failed to terminate AF [71.3 (67.5-77.8) vs. 82.4 (74.4-98.5) ms; p = 0.0126]. ACI predicted AD [AUC 0.728 (0.629-0.826)]. An ACI < 70 ms was specific for predicting AD (Sp 0.831, Se 0.526), whereas areas with an ACI > 100 ms had almost no chances of being active in AF maintenance. AF recurrence was associated with more ACI zones with identical shortest value [3.5 (3-4) vs. 1 (0-1) zones; p = 0.021]. In multivariate analysis, ACI < 70 ms predicted AD [OR = 4.02 (1.49-10.84), p = 0.006] and mean ACI > 75 ms predicted AF termination [OR = 9.94 (1.14-86.7), p = 0.038]. ACI helps in identifying AF drivers, and is correlated with AF termination and AF recurrence during follow-up. It can help in establishing an ablation plan, by prioritizing ablation from the shortest to the longest ACI zone.

Impact of Obesity on Atrial Electrophysiological Substrate.

(1) Background. Obesity is a well-established worldwide recognised risk factor for atrial fibrillation (AF). Prior review papers reported on the associations between obesity and AF development, but not on the relation between obesity and atrial electrophysiology. We therefore conducted a systematic review to describe the current knowledge of the characteristics of the atrial electrophysiological substrate in obese individuals and how they relate to the development of AF. (2) Methods. A search was conducted in Pubmed, Embase, and the Cochrane Library for publications evaluating the impact of obesity on atrial electrophysiology, electrical substrates, and their relation to the development of AF. (3) Results. A systematic literature search retrieved 477 potential publications based on the inclusion criteria; 76 full-text articles were selected for the present systematic review. The literature demonstrated that obesity predisposes to not only a higher AF incidence but also to more extensive atrial electrophysiological abnormalities increasing susceptibility to AF development. (4) Conclusion. Obesity may predispose to an overall increase in atrial electropathology, consisting of an increase in the slowing of the conduction, conduction block, low-voltage areas, and complex fractionated electrograms. To determine the impact of obesity-induced atrial electrical abnormalities on the long-term clinical outcome, further prospective studies are mandatory.

Gender-Related Differences in Atrial Substrate in Patients with Atrial Fibrillation

Gender-related differences have been reported in patients who underwent pulmonary vein isolation (PVI). Atrial substrate plays a role in the outcomes after ablation but gender-related differences in atrial substrate have never been described in detail. We sought to analyze gender-related differences in atrial remodeling (spontaneous low-voltage zones [LVZs]) and their clinical relevance after PVI. We conducted a prospective multicenter study, including consecutive patients who underwent first PVI-only atrial fibrillation (AF) ablation. LVZs were analyzed on high-density electroanatomical maps collected with multipolar catheter, before PVI. In total, 262 patients (61 ± 11years, 31% female, 50% persistent AF) were followed for 28months. In women, LVZs were larger (10% vs 4% of left atrial surface [p<0.001]) and female gender was independently associated with fourfold higher risk of having advanced (LVZ > 15%) atrial remodeling (odds ratio 4.56, p<0.001). AF recurrence-free survival was not different between men and women (log-rank p=0.2). Although LVZs were independently associated higher AF recurrences at multivariate analysis (hazard ratio [HR] 1.2, p=0.038), female gender was not (HR 1.4, p=0.211). Specifically, the LVZ cutoff to predict outcomes was different in men and women: >5% in men (HR 3.0, p<0.001), >15% in women (HR 2.7, p=0.02). In conclusion, women have more widespread LVZ in all left atrial regions. Despite more extensive atrial remodeling, the AF recurrence rate is similar in men and women, and LVZs become prognostic in women only at high burden (>15%). LVZs seem to have a different prognostic role in men and women.

Does the spatial distribution of atrial arrhythmogenic substrate matter? Insights from the DECAAF II trial.

Does the spatial distribution of atrial arrhythmogenic substrate matter? Insights from the DECAAF II trial.

Differences in atrial substrate localization using late gadolinium enhancement-magnetic resonance imaging, electrogram voltage, and conduction velocity: a cohort study using a consistent anatomical reference frame in patients with persistent atrial fibrillation.

Electro-anatomical voltage, conduction velocity (CV) mapping, and late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) have been correlated with atrial cardiomyopathy (ACM). However, the comparability between these modalities remains unclear. This study aims to (i) compare pathological substrate extent and location between current modalities, (ii) establish spatial histograms in a cohort, (iii) develop a new estimated optimized image intensity threshold (EOIIT) for LGE-MRI identifying patients with ACM, (iv) predict rhythm outcome after pulmonary vein isolation (PVI) for persistent atrial fibrillation (AF). Thirty-six ablation-naive persistent AF patients underwent LGE-MRI and high-definition electro-anatomical mapping in sinus rhythm. Late gadolinium enhancement areas were classified using the UTAH, image intensity ratio (IIR >1.20), and new EOIIT method for comparison to low-voltage substrate (LVS) and slow conduction areas <0.2 m/s. Receiver operating characteristic analysis was used to determine LGE thresholds optimally matching LVS. Atrial cardiomyopathy was defined as LVS extent ≥5% of the left atrium (LA) surface at <0.5 mV. The degree and distribution of detected pathological substrate (percentage of individual LA surface are) varied significantly (P < 0.001) across the mapping modalities: 10% (interquartile range 0-14%) of the LA displayed LVS <0.5 mV vs. 7% (0-12%) slow conduction areas <0.2 m/s vs. 15% (8-23%) LGE with the UTAH method vs. 13% (2-23%) using IIR >1.20, with most discrepancies on the posterior LA. Optimized image intensity thresholds and each patient's mean blood pool intensity correlated linearly (R2 = 0.89, P < 0.001). Concordance between LGE-MRI-based and LVS-based ACM diagnosis improved with the novel EOIIT applied at the anterior LA [83% sensitivity, 79% specificity, area under the curve (AUC): 0.89] in comparison to the UTAH method (67% sensitivity, 75% specificity, AUC: 0.81) and IIR >1.20 (75% sensitivity, 62% specificity, AUC: 0.67). Discordances in detected pathological substrate exist between LVS, CV, and LGE-MRI in the LA, irrespective of the LGE detection method. The new EOIIT method improves concordance of LGE-MRI-based ACM diagnosis with LVS in ablation-naive AF patients but discrepancy remains particularly on the posterior wall. All methods may enable the prediction of rhythm outcomes after PVI in patients with persistent AF.

CLOSE-Guided Pulmonary Vein Isolation to Treat Persistent Atrial Fibrillation: 1-Year Outcome.

CLOSE-guided pulmonary vein isolation (PVI) is based on contiguous and optimized (Ablation Index-guided) radiofrequency lesions. The efficacy of CLOSE-guided PVI in persistent atrial fibrillation (AF) treatment has been poorly evaluated. In two centers, 50 patients eligible for persistent AF ablation underwent CLOSE-guided PVI (Ablation Index ≥ 450 at the anterior wall, ≥300 at posterior wall, intertag distance ≤ 6 mm). If PVI failed to restore sinus rhythm (SR), electrical cardioversion (ECV) was performed. Atrial substrate modification (ASM) was performed only if PVI and ECV failed to restore SR. Recurrence was defined as any recorded episode of AF, atrial tachycardia (AT) or atrial flutter (AFL) > 30 s on Holter electrocardiographs at 3, 6 and 12 months. From the 50 patients (64 ± 10 years, 14% long-standing persistent AF), SR was restored by ECV in 34 patients (68%) 56 ± 38 days prior to ablation. On the day of ablation, 42 patients (84%) were on class I-III anti-arrhythmic drug therapy (ADT) and the rhythm was AF in 23/50 patients. PVI was achieved in all patients; after PVI, ECV was required in 21 patients and ASM in 1 patient. The mean procedure time, radiofrequency time and fluoroscopy time were 141 ± 33 min, 23 ± 7 min and 7 ± 6 min, respectively. At 12 months, single-procedure freedom from AF/AT/AFL was 80%, with 19 patients (38%) receiving class I-III ADT. In a population of patients with persistent AF monitored with intermittent cardiac rhythm recordings, CLOSE-guided PVI resulted in high single-procedure arrhythmia-free survival at 1 year. Future large-scale studies involving continuous cardiac monitoring are necessary.

Left atrial conduction times and regional velocities in persistent atrial fibrillation patients with and without fibrotic atrial cardiomyopathy

Despite the progress in understanding left atrial substrate and arrhythmogenesis, only little is known about conduction characteristics in atrial fibrillation patients with various stages of fibrotic atrial cardiomyopathy (FACM). This study evaluates left atrial conduction times and conduction velocities based on high-density voltage and activation maps in sinus rhythm (CARTO®3 V7) of 53 patients with persistent atrial fibrillation (LVEF 60% (55–60 IQR), LAVI 39 ml/m2 (31–47 IQR), LApa 24 ± 6 cm2). Measurements were made in low voltage areas (LVA ≤ 0.5 mV) and normal voltage areas (NVA ≥ 1.5 mV) at the left atrial anterior and posterior walls. Maps of 28 FACM and 25 no FACM patients were analyzed (19 FACM I/II, 9 FACM III/IV, LVA 14 ± 11 cm2). Left atrial conduction time averaged to 110 ± 24 ms but was shown to be prolonged in FACM (119 ms, + 17%) when compared to no FACM patients (101 ms, p = 0.005). This finding was pronounced in high-grade FACM (III/IV) (133 ms, + 31.2%, p = 0.001). In addition, the LVA extension correlated significantly with the left atrial conduction time (r = 0.56, p = 0.002). Conduction velocities were overall slower in LVA than in NVA (0.6 ± 0.3 vs. 1.3 ± 0.5 m/s, -51%, p < 0.001). Anterior conduction appeared slower than posterior, which was significant in NVA (1 vs. 1.4 m/s, -29%, p < 0.001) but not in LVA (0.6 vs. 0.8 m/s, p = 0.096). FACM has a significant influence on left atrial conduction characteristics in patients with persistent atrial fibrillation. Left atrial conduction time prolongs with the grade of FACM and the quantitative expanse of LVA up to 31%. LVAs show a 51% conduction velocity reduction compared to NVA. Moreover, regional conduction velocity differences are present in the left atrium when comparing anterior to posterior walls. Our data may influence individualized ablation strategies.