Machine learning identifies esophageal luminal temperature patterns associated with thermal injury in catheter ablation for atrial fibrillation.

INTRODUCTION: Luminal esophageal temperature (LET) monitoring during atrial fibrillation (AF) ablation is widely used to reduce the incidence of endoscopically detected esophageal lesion (EDEL). We sought to assess whether specific patterns of LET variation are associated with EDEL. METHODS: A high-fidelity multisensor probe was used to record LET in AF patients undergoing radiofrequency ablation (RFA) or cryoballoon ablation (CBA). Explainable machine learning and SHapley Additive exPlanations (SHAP) analysis were used to predict EDEL and assess feature importance. RESULTS: A total of 94 patients (38.3% persistent AF, 71.3% male, 72 RFA, and 22 CBA) were included. EDEL was detected in 11 patients (10 RFA and one CBA). In the RFA group, the highest LET recorded was similar between patients with and without EDEL (40.6 [40.1-41]°C vs. 40.2 [39.1-40.9]°C; p = .313), however, the rate of LET rise for the highest recorded peak was higher (0.08 [0.03-0.12]°C/s vs. 0.02 [0.01-0.05]°C/s; p = .033), and the area under the curve (AUC) for the highest peak was smaller (412.5 [206.8-634.1] vs. 588.6 [380.4-861.1]; p = .047) in patients who had EDEL. In case of CBA, the patient with EDEL had a faster LET decline (0.12 vs. 0.07 [0.02-0.14]°C/s), and a smaller AUC for the lowest trough (2491.3 vs. 2629.3 [1712.6-5283.2]). SHAP analysis revealed that a rate of LET change higher than 0.05°C/s and an AUC less than 600 were more predictive of EDEL in RFA. CONCLUSION: The rate of LET change and AUC for the recorded temperature predicted EDEL, whereas absolute peak temperatures did not.

Network meta-analysis and systematic review comparing efficacy and safety between very high power short duration, high power short duration, and conventional radiofrequency ablation of atrial fibrillation.

BACKGROUND: High-power short-duration (HPSD) atrial fibrillation (AF) ablation with a power of 40-50 W was proved to be safe and effective. Very high-power short-duration (vHPSD) AF ablation is a novel method using >50 W to obtain more durable AF ablation. This study aimed to evaluate the efficacy and safety of vHPSD ablation compared with HPSD ablation and conventional power ablation. METHODS: A literature search for studies that reported AF ablation outcomes, including short-term freedom from atrial arrhythmia, first-pass isolation (FPI) rate, procedure time, and major complications, was conducted utilizing MEDLINE, EMBASE, and Cochrane databases. All relevant studies were included in this analysis. A random-effects model of network meta-analysis and surface under cumulative ranking curve (SUCRA) were used to rank the treatment for all outcomes. RESULTS: A total of 29 studies with 9721 patients were included in the analysis. According to the SUCRA analysis, HPSD ablation had the highest probability of maintaining sinus rhythm. Point estimation showed an odds ratio of 1.5 (95% confidence interval [CI]: 1.2-1.9) between HPSD ablation and conventional power ablation and an odds ratio of 1.3 (95% CI: 0.78-2.2) between vHPSD ablation and conventional power ablation. While the odds ratio of FPI between HPSD ablation and conventional power ablation was 3.6 (95% CI: 1.5-8.9), the odds ratio between vHPSD ablation and conventional power ablation was 2.2 (95% CI: 0.61-8.6). The procedure times of vHPSD and HPSD ablations were comparable and, therefore, shorter than that of conventional power ablation. Major complications were low in all techniques. CONCLUSION: vHPSD ablation did not yield higher efficacy than HPSD ablation and conventional power ablation. With the safety concern, vHPSD ablation outcomes were comparable with those of other techniques.

Elevated fibrosis burden as assessed by MRI predicts cryoballoon ablation failure.

INTRODUCTION: Late-gadolinium enhancement magnetic resonance (LGE-MRI) imaging is increasingly used in management of atrial fibrillation (AFib) patients. Here, we assess the usefulness of LGE-MRI-based fibrosis quantification to predict arrhythmia recurrence in patients undergoing cryoballoon ablation. Our secondary goal was to compare two widely used fibrosis quantification methods. METHODS: In 102 AF patients undergoing LGE-MRI and cryoballoon ablation (mean age 62 years; 64% male; 59% paroxysmal AFib), atrial fibrosis was quantified using the pixel intensity histogram (PIH) and image intensity ratio (IIR) methods. PIH segmentations were completed by a third-party provider as part of the standard of care at our hospital; Image intensity ratio (IIR) segmentations of the same scans were carried out in our lab using a commercially available software package. Fibrosis burdens and spatial distributions for the two methods were compared. Patients were followed prospectively for recurrent arrhythmia following ablation. RESULTS: Average PIH fibrosis was 15.6 ± 5.8% of the left atrial (LA) volume. Depending on threshold (IIRthr ), the average IIR fibrosis (% of LA wall surface area) ranged from 5.0 ± 7.2% (IIRthr = 1.2) to 37.4 ± 10.9% (IIRthr = 0.97). An IIRthr of 1.03 demonstrated the greatest agreement between the methods, but spatial overlap of fibrotic areas delineated by the two methods was modest (Sorenson Dice coefficient: 0.49). Fourty-two patients (41.2%) had recurrent arrhythmia. PIH fibrosis successfully predicted recurrence (HR 1.07; p = .02) over a follow-up period of 362 ± 149 days; regardless of IIRthr , IIR fibrosis did not predict recurrence. CONCLUSIONS: PIH-based volumetric assessment of atrial fibrosis was modestly predictive of arrhythmia recurrence following cryoballoon ablation in this cohort. IIR-based fibrosis was not predictive of recurrence for any of the IIRthr values tested, and the overlap in designated areas of fibrosis between the PIH and IIR methods was modest. Caution must therefore be exercised when interpreting LA fibrosis from LGE-MRI, since the values and spatial pattern are methodology-dependent.

Positional obstructive sleep apnea in patients with atrial fibrillation.

PURPOSE: Obstructive sleep apnea (OSA) is a common, potentially modifiable condition implicated in the pathogenesis of atrial fibrillation (AF). The presence and severity of OSA is largely sleep position-dependent, yet there is high variability in positional dependence among patients with OSA. We investigated the prevalence of positional OSA (POSA) and examined associated factors in patients with AF. METHODS: We recruited an equal number of patients with and without AF who underwent diagnostic polysomnography. Patients included had ≥ 120 min of total sleep time with 30 min of sleep in both supine and lateral positions. POSA was defined as an overall apnea hypopnea index (AHI) ≥ 5/h, supine AHI (sAHI) ≥ 5/h, and sAHI greater than twice the non-supine AHI. POSA prevalence was compared in patients with and without AF adjusting for age, sex, OSA severity, and heart failure. RESULTS: A total of patients (male: 56%, mean age 62 years) were included. POSA prevalence was similar between the two groups (46% vs. 39%; p = 0.33). Obesity and severe OSA (AHI ≥ 30/h) were associated with low likelihood of POSA (OR [CI] of 0.17 [0.09-0.32] and 0.28 [0.12-0.62]). In patients with AF, male sex was associated with a higher likelihood of POSA (OR [CI] of 3.16 [1.06-10.4]). CONCLUSION: POSA is common, affecting more than half of patients with AF, but the prevalence was similar in those without AF. Obesity and more severe OSA are associated with lower odds of POSA. Positional therapy should be considered in patients with mild OSA and POSA.

Catheter ablation for atrial fibrillation in the elderly >75 years old: Systematic review and meta-analysis.

INTRODUCTION: Atrial fibrillation (AF) ablation is increasingly performed worldwide. As comfort with AF ablation increases, the procedure is increasingly used in patients that are older and in those with more comorbidities. However, it is not well established whether AF ablation in the elderly, especially those >75 years old, has comparable safety and efficacy to younger populations. OBJECTIVE: To compare the efficacy and safety profiles in patients older than 75 years undergoing AF ablation with younger patients. METHODS: Databases from EMBASE, Medline, PubMed, and Cochrane, were searched from inception through September 2021. Studies that compared the success rates in AF catheter ablation and all complications rates between patients who were older vs under 75 years were included. Effect estimates from the individual studies were extracted and combined using random effect, generic inverse variance method of DerSimonian and Laird. RESULTS: Twenty-seven observational studies were included in the analysis consisting of 363,542 patients who underwent AF ablation. Comparing patients older than 75 years old to younger patients, there was no difference in the success of ablation rates between elderly and younger patients (pooled OR 0.85: 95% CI:0.69-1.05, p = .131). On the other hand, AF ablation in the elderly was associated with higher complication rates (pooled OR 1.42: 95% CI:1.21-1.68, p < .001). CONCLUSION: As AF ablation is expanded to elderly populations, our study found that AF ablation success rates were similar in both elderly and younger patients. However, older patients experience higher rates of complications that should be considered when offering the procedure and as a means to improve outcomes with future innovations.

Effect of MRI-Guided Fibrosis Ablation vs Conventional Catheter Ablation on Atrial Arrhythmia Recurrence in Patients With Persistent Atrial Fibrillation: The DECAAF II Randomized Clinical Trial.

Importance: Ablation of persistent atrial fibrillation (AF) remains a challenge. Left atrial fibrosis plays an important role in the pathophysiology of AF and has been associated with poor procedural outcomes. Objective: To investigate the efficacy and adverse events of targeting atrial fibrosis detected on magnetic resonance imaging (MRI) in reducing atrial arrhythmia recurrence in persistent AF. Design, Setting, and Participants: The Efficacy of Delayed Enhancement-MRI-Guided Fibrosis Ablation vs Conventional Catheter Ablation of Atrial Fibrillation trial was an investigator-initiated, multicenter, randomized clinical trial involving 44 academic and nonacademic centers in 10 countries. A total of 843 patients with symptomatic or asymptomatic persistent AF and undergoing AF ablation were enrolled from July 2016 to January 2020, with follow-up through February 19, 2021. Interventions: Patients with persistent AF were randomly assigned to pulmonary vein isolation (PVI) plus MRI-guided atrial fibrosis ablation (421 patients) or PVI alone (422 patients). Delayed-enhancement MRI was performed in both groups before the ablation procedure to assess baseline atrial fibrosis and at 3 months postablation to assess for ablation scar. Main Outcomes and Measures: The primary end point was time to first atrial arrhythmia recurrence after a 90-day blanking period postablation. The primary safety composite outcome was defined by the occurrence of 1 or more of the following events within 30 days postablation: stroke, PV stenosis, bleeding, heart failure, or death. Results: Among 843 patients who were randomized (mean age 62.7 years; 178 [21.1%] women), 815 (96.9%) completed the 90-day blanking period and contributed to the efficacy analyses. There was no significant difference in atrial arrhythmia recurrence between groups (fibrosis-guided ablation plus PVI patients, 175 [43.0%] vs PVI-only patients, 188 [46.1%]; hazard ratio [HR], 0.95 [95% CI, 0.77-1.17]; P = .63). Patients in the fibrosis-guided ablation plus PVI group experienced a higher rate of safety outcomes (9 [2.2%] vs 0 in PVI group; P = .001). Six patients (1.5%) in the fibrosis-guided ablation plus PVI group had an ischemic stroke compared with none in PVI-only group. Two deaths occurred in the fibrosis-guided ablation plus PVI group, and the first one was possibly related to the procedure. Conclusions and Relevance: Among patients with persistent AF, MRI-guided fibrosis ablation plus PVI, compared with PVI catheter ablation only, resulted in no significant difference in atrial arrhythmia recurrence. Findings do not support the use of MRI-guided fibrosis ablation for the treatment of persistent AF. Trial Registration: ClinicalTrials.gov Identifier: NCT02529319.

High-power short duration and low-power long duration in atrial fibrillation ablation: A meta-analysis.

BACKGROUND: Multiple strategies have advocation for power titration and catheter movement during atrial fibrillation (AF) ablation. Comparative favoring evidence regarding the efficacy, logistics, and safety of a higher-power, shorter duration (HPSD) ablation strategy compared to a lower-power, longer duration (LPLD) ablation strategy is insubstantial. We performed a meta-analysis to compare arrhythmia-free survival, procedure times, and complication rates between the two strategies. METHODS: We searched MEDLINE, EMBASE, and Cochrane Library from inception to September 2020. We included studies comparing patients who underwent HPSD and LPLD strategies for AF ablation and reporting either of the following outcomes: Freedom from atrial tachyarrhythmia (AT) including AF and atrial flutter, procedure time, or periprocedural complications. We combined data using the random-effects model to calculate the odds ratio (OR) and weight mean difference (WMD) with a 95% confidence interval (CI). RESULTS: Ten studies from 2006 to 2020 involving 2274 patients were included (1393 patients underwent HPSD strategy and 881 patients underwent LPLD strategy). HPSD strategy was not associated with increased freedom from AT at 12-month follow-up (OR = 1.54, 95% CI: 0.99 to 2.40, p = .054). In the subgroup analysis of the randomized controlled trial, the HPSD strategy was associated with increased freedom from AT compared to the LPLD strategy (OR = 3.12, 95% CI: 1.18 to 8.20, p = .02). There was a significant reduction in the HPSD group for the total procedure (WMD = 49.60, 95% CI: 29.76 to 69.44) and ablation (WMD = 17.92, 95% CI: 13.63 to 22.22) times, but not for fluoroscopy time (WMD = 1.15, 95% CI: -0.67 to 2.97). HPSD was not associated with a reduction in esophageal ulcer/atrioesophageal fistula (OR = 0.35, 95% CI: 0.12 to 1.06) or pericardial effusion/cardiac tamponade rates (OR = 1.16, 95% CI: 0.35 to 3.81). CONCLUSIONS: When compared to the LPLD strategy, the HPSD strategy does not improve recurrent AT nor reduce periprocedural complication risks. However, subgroup analysis of the randomized controlled trial showed that HPSD significantly reduces AT recurrence. An HPSD strategy can significantly reduce total procedure and ablation times.

Effect of DrOnedarone on atrial fibrosis progression and atrial fibrillation recurrence postablation: Design of the EDORA randomized clinical trial.

BACKGROUND: Atrial fibrillation (AF) recurrence after catheter ablation is associated with worse outcomes and quality of life. Left atrial (LA) structural remodeling provides the essential substrate for AF perpetuation. Baseline extent and the progression of LA fibrosis after ablation are strong predictors of postprocedural AF recurrence. Dronedarone is an antiarrhythmic drug proven to efficiently maintain sinus rhythm. OBJECTIVE: We sought to investigate the effect of the antiarrhythmic drug Dronedarone in decreasing LA fibrosis progression and AF recurrence after ablation of AF patients. METHODS: EDORA (NCT04704050) is a multicenter, prospective, randomized controlled clinical trial. Patients with persistent or paroxysmal AF undergoing AF ablation will be randomized into Dronedarone versus placebo/standard of care. The co-primary outcomes are the recurrence of atrial arrhythmias (AA) within 13 months of follow-up after ablation and the progression of left atrial fibrosis postablation. All patients will receive a late-gadolinium enhancement magnetic resonance imaging at baseline, 3- and 12-month follow-up for the quantification of LA fibrosis and ablation-related scarring. AA recurrence and burden will be assessed using a 30-day ECG patch every 3 months with daily ECG recordings in between. Quality of life improvement is assessed using the AFEQT and AFSS questionnaires. CONCLUSION: EDORA will be the first trial to assess the progression of LA structural remodeling after ablation and its association with Dronedarone treatment and ablation success in a randomized controlled fashion. The trial will provide insight into the pathophysiology of AF recurrence after ablation and may provide potential therapeutic targets to optimize procedural outcomes.

Efficacy of LGE-MRI-guided fibrosis ablation versus conventional catheter ablation of atrial fibrillation: The DECAAF II trial: Study design.

INTRODUCTION: Success rates of catheter ablation in persistent atrial fibrillation (AF) remain suboptimal. A better and more targeted ablation strategy is urgently needed to optimize outcomes of AF treatment. We sought to assess the safety and efficacy of targeting atrial fibrosis during ablation of persistent AF patients in improving procedural outcomes. METHODS: The DECAAF II trial (ClinicalTrials. gov identifier number NCT02529319) is a prospective, randomized, multicenter trial of patients with persistent AF. Patients with persistent AF undergoing a first-time ablation procedure were randomized in a 1:1 fashion to receive conventional pulmonary vein isolation (PVI) ablation (Group 1) or PVI + fibrosis-guided ablation (Group 2). Left atrial fibrosis and ablation induced scarring were defined by late gadolinium enhancement magnetic resonance imaging at baseline and at 3-12 months postablation, respectively. The primary endpoint is the recurrence of atrial arrhythmia postablation, including atrial fibrillation, atrial flutter, or atrial tachycardia after the 90-day postablation blanking period. Patients were followed for a period of 12-18 months with a smartphone ECG Device (ECG Check Device, Cardiac Designs Inc.). With an anticipated enrollment of 900 patients, this study has an 80% power to detect a 26% reduction in the hazard ratio of the primary endpoint. RESULTS AND CONCLUSION: The DECAAF II trial is the first prospective, randomized, multicenter trial of patients with persistent AF using imaging defined atrial fibrosis as a treatment target. The trial will help define an optimal approach to catheter ablation of persistent AF, further our understanding of influencers of ablation lesion formation, and refine selection criteria for ablation based on atrial myopathy burden.

Atrial fibrosis in embolic stroke of undetermined source: A multicenter study.

BACKGROUND AND PURPOSE: Left atrial (LA) cardiac disease is a suspected cause of embolic stroke of undetermined source (ESUS). We tested the hypothesis that LA fibrosis, quantified using late-gadolinium-enhancement magnetic resonance imaging (LGE-MRI), predicts recurrent stroke or atrial fibrillation (AF) in patients with ESUS. METHODS: We compared atrial fibrosis in healthy controls and patients with lacunar stroke, ESUS, and known AF with or without prior stroke. We followed patients with ESUS prospectively for the primary outcome of recurrent ischemic stroke, incident AF, or both. RESULTS: We enrolled 203 patients from three centers: 103 patients without AF (35 healthy controls, 15 with lacunar strokes, 53 with ESUS) and 100 patients with AF (50 with and 50 without prior stroke). Patients with ESUS had significantly higher atrial fibrosis (15.0 ± 6.2%) compared to healthy controls (8.1 ± 7.9%; <0.0001) and compared to lacunar stroke patients (10.8 ± 8.4; p = 0.02), but had comparable fibrosis to patients with AF with (17.9 ± 11.4%) or without prior stroke (16.6 ± 9.2%; p = NS for both). Over a mean follow-up of 19 months, nine of 53 patients (16.9%) with ESUS experienced the combined primary outcome, which included six patients (11.3%) with recurrent ischemic stroke and five patients with incident AF (9.4%). Patients with ESUS with fibrosis ≥12% had a higher proportion of the combined outcome: 25.0% vs. 4.8%; p = 0.039. CONCLUSIONS: Patients with ESUS demonstrate atrial fibrosis comparable to that seen in AF. Atrial fibrosis ≥12% was associated with recurrent stroke, incident AF or both. This subgroup of ESUS patients may benefit from anticoagulation for secondary prevention of ischemic stroke.

Dynamic voltage threshold adjusted substrate modification technique for complex atypical atrial flutters with varying circuits.

BACKGROUND: Atypical atrial flutter (AFL) is common in patients with postsurgical atrial scar, with macro- or microscopic channels in the scar acting as substrate for reentry. Heterogeneous atrial scarring can cause varying flutter circuits, which makes mapping and ablation challenging, and recurrences common. AIM: We hypothesize that dynamically adjusting voltage thresholds can identify heterogeneous atrial scarring, which can then be effectively homogenized to eliminate atypical AFLs. METHODS: We studied consecutive patients who presented to Electrophysiology laboratory for atypical AFL ablation with history of atriotomy and included the patients with multiple, varying flutter circuits during mapping in our study. We excluded patients with stable flutter circuit that was sustained and could be localized using traditional entrainment and activation mapping strategy. In the included patients, we performed detailed high-density voltage map of the atrium of interest. We adjusted voltage thresholds as needed to identify heterogeneity and channels in the scarred regions. A thorough scar homogenization was performed with irrigated smart-touch ablation catheter. Re-inducibility of tachycardia, and immediate and long-term outcomes were studied. RESULTS: Of five studied cases, one was female; age 66 ± 10 years. All five had prior surgical substrate. All the patients had multiple flutter morphologies, which varied as we mapped the AFL. After scar homogenization, tachycardia was not inducible in any patient. No recurrence of flutter was noted during a mean follow-up duration of 450 ± 27 days. CONCLUSION: High-density voltage mapping and homogenization of the scar can be an effective strategy in eliminating complex scar-mediated atypical AFL with multiple circuits.

Electrocardiographic left atrial abnormality in patients presenting with ischemic stroke.

BACKGROUND: P wave indices represent electrocardiographic marker of left atrial pathology. We hypothesized that P wave would be more abnormal in patients presenting with ischemic stroke than a comparable group without ischemic stroke. METHODS: We compared P wave terminal force in V1 (PTFV1) between patients admitted with ischemic stroke (case) and patients followed in cardiology clinic (control) at a single medical center. Using logistic regression models, we tested for an association between abnormal PTFV1 (> 4000 µV ms) and ischemic stroke. We also defined several optimal cut-off values of PTFV1 using a LOESS plot and estimated odds ratio of ischemic stroke when moving from one cut-point level to the next higher-level. RESULTS: A total of 297 patients (case 147, control 150) were included. PTFV1 was higher in patients with vs. those without ischemic stroke (median 4620 vs 3994 µV ms; p=0.006). PTFV1 was similar between cardioembolic/cryptogenic and other stroke subtypes. In multivariable analyses adjusting for sex, obesity, age, and hypertension, the association between abnormal PTFV1 and ischemic stroke ceased to be significant (OR 1.53 [0.95, 2.50], p=0.083). Increase to the next cutoff level of PTFV1 (900, 2000, 3000, 4000, 5000, and 6000 µV ms) was associated with 18% increase in odds of having ischemic stroke (vs. no ischemic stroke) (OR 1.18 [1.02, 1.36], p=0.026). CONCLUSION: Patients presenting with acute ischemic stroke are more likely to have abnormal PTFV1. These findings from a real-world clinical setting support the results of cohort studies that left atrial pathology manifested as abnormal PTFV1 is associated with ischemic stroke.

Age and sex differences in atrial fibrosis among patients with atrial fibrillation.

Aim: Age and female sex are associated with a higher risk of stroke in atrial fibrillation (AF). We sought to determine whether advancing age and female sex are associated with higher atrial fibrosis. Methods and results: We conducted an observational cohort study of patients with AF enrolled in the University of Utah AF Database and a non-AF control group who underwent late-gadolinium enhancement magnetic resonance imaging (LGE-MRI) for atrial fibrosis quantification. Participants with contra-indications for contrast MRI scanning were excluded. Nine hundred and eight consecutive men and women with AF and 15 non-AF controls were included in this study. Left atrial fibrosis increased with age in both men and women with AF. Women with AF (n = 316) were older than men (n = 592): mean age 68.7±11.6 vs. 64.9±11.7 years; P < 0.01, and had higher left atrial fibrosis compared with men 17.5 ± 10.1% vs. 15.3 ± 8.9%; P < 0.001. Women also had a higher prevalence of prior stroke compared with men (15.8% vs. 6.5%; P < 0.001). Age and sex relationships with atrial fibrosis remained significant in multivariate analysis. Compared with the non-AF control group, patients with AF had significantly higher atrial fibrosis: 16.0 ± 9.4 vs. 5.5 ± 5.8%; P < 0.001. Conclusions: Advancing age and female sex are associated with a higher burden of atrial fibrosis in patients with AF. Women with a prior history of stroke also have higher fibrosis compared with both women and men without history of stroke. Advanced fibrosis may explain the female and age association with stroke in AF.

Computational simulations of asymmetric fluxes of large molecules through gap junction channel pores.

Gap junction channels are formed out of connexin isoforms, which enable molecule and ion selective diffusion amongst neighboring cells. HeLa cells expressing distinct connexins (Cx) allow the formation of heterotypic channels, where we observed a molecular charge-independent preferential flux of large fluorescent molecules in the Cx45 to Cx43 direction. We hypothesize that the pore's shape is a significant factor along-side charge and transjunctional voltages for this asymmetric flux. To test this hypothesis, we developed a 3D computational model simulating Brownian diffusion of large molecules in a gap junction channel pore. The basic pore contour was derived from x-ray crystallographic structures of Cx43 and Cx26 and approximated using basic geometric shapes. Lucifer yellow dye molecules and cesium counter-ions were modeled as spheres using their respective Stokes radii. Our simulation results from simple diffusion and constant concentration gradient experiments showed that only charged particles yield asymmetric fluxes in heterotypic pores. While increasing the inner mouth size resulted in a near-quadratic rise in flux, the rise was asymptotic for outer mouth radii increase. Probability maps and average force per particle per pore section explain the asymmetric flux with variation in pore shape. Furthermore, the simulation results are in agreement with our in vitro experimental results with HeLa cells in Cx43-Cx45 heterotypic configurations. The presence of asymmetric fluxes can help us to understand effects of the molecular structure of the pore and predict potential differences in vivo.

Left Atrial Geometry Improves Risk Prediction of Thromboembolic Events in Patients With Atrial Fibrillation.

BACKGROUND: Left atrial (LA) sphericity (LASP) is a new remodeling parameter based on LA shape analysis, with independent predictive value for recurrence after atrial fibrillation (AF) ablation. OBJECTIVES: To evaluate the association between LASP and thromboembolic events (TE) in patients with AF. METHODS: Twenty-nine AF patients and prior TE and 29 age- and gender-matched controls were included. LASP was calculated using a 3D-LA reconstruction. The LA appendage (LAA) volume and morphology were assessed. ROC curve analysis was performed for LASP, LA volume, LAA volume, and CHAD/CHA2 D-VASc scores (Stroke2 -the grouping variable-was excluded). RESULTS: Mean age of the study population was 61 ± 11 years (79.3% males, 53.4% hypertension, 8.6% diabetes). Patients with prior TE had higher LASP than those without (82.5 ± 3.3% vs. 80.2 ± 3.1%, P = 0.008); there were no differences in CHAD or CHA2 D-VASc scores, LA volume, LAA volume, or LAA morphology. The C-statistic was higher for LASP (0.71) than for other tested variables (CHAD score = 0.58, CHA2 D-VASc score = 0.59, LA volume = 0.50, LAA volume = 0.46; P < 0.01 for all vs. LASP). The best cutoff value for LASP was 83.6% (sensitivity 0.52, specificity 0.90). Logistic regression analysis showed predictive value for LASP (OR 1.26 per each 1% increase [1.85-52.20], P = 0.013), but not for clinical risk scores. The addition of LASP to the CHAD and CHA2 D-VASc scores increased the predictive value over the risk scores alone (P = 0.004), and reclassified 45.5% of patients with CHAD = 0 (no anticoagulation indicated) to moderate-risk (anticoagulation indicated). CONCLUSION: LA sphericity is associated with prior TE in AF patients and improves the performance of the CHAD and CHA2 D-VASc scores alone.