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The relationship between atrial fibrillation (AF) and dementia has been well described; however, recent data suggest that AF confers a greater risk for the development of early-onset dementia irrespective of clinical stroke. Numerous mechanisms have been hypothesized to explain cognitive decline in the setting of AF, including silent cerebral ischemia, cerebral hypoperfusion, and cerebral microvascular disease. Despite the emergence of data supporting the increased risk of early-onset dementia in patients with AF, the underlying mechanism remains unclear. Furthermore, the mechanism may be influenced by survival bias, genetic susceptibility, or early dysfunction of brain adaptation. Investigation into why this relationship exists could change how prevention and treatment are evaluated., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Atrial fibrillation (AF) is significantly associated with morbidity and mortality and erodes the quality and quantity of life. It is standard of care to treat patients with AF and an increased risk of stroke with oral anticoagulation therapy, but the more daunting question many clinicians face is whether to pursue a "rate-only" or "rhythm" control strategy. Historical studies over the years have sought to answer this question but have found no significant difference in major clinical outcomes between the two strategies. There are opportunities based on new data to improve the natural history of the disease. The EAST AFnet trial for the first time revealed a significant morbidity and mortality advantage to rhythm control therapy when performed early in the disease process of AF and in the setting of comprehensive medical management that was maintained. The CABANA trial clearly demonstrated that catheter ablation was a more effective long-term treatment of AF in general and significantly lowers risk of AF progression compared to medical therapy. Like multiple prior trials of rhythm management strategies, when rhythm control was effective in these trials, independent of therapy assignment, there was a significantly lower risk of adverse outcomes and death. These contemporary data provide optimism that the pervasive mortality risk in patients with AF observed over the past 50 years may be improved by the timing, use, and efficacy of use of therapeutic interventions., (© 2023 Wiley Periodicals LLC.)

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., (© 2023 Wiley Periodicals LLC.)

Introduction: Atrial Fibrillation (AF) is a common arrhythmia often comorbid with systolic or diastolic heart failure (HF). Catheter ablation is a more effective treatment for AF with concurrent left ventricular dysfunction, however, the optimal timing of use in these patients is unknown., Methods: All patients that received a catheter ablation for AF(n = 9979) with 1 year of follow-up within the Intermountain Healthcare system were included. Patients with were identified by the presence of structural disease by ejection fraction (EF): EF ≤ 35% (n = 1024) and EF > 35% (n = 8955). Recursive partitioning categories were used to separate patients into clinically meaningful strata based upon time from initial AF diagnosis until ablation: 30-180(n = 2689), 2:181-545(n = 1747), 3:546-1825(n = 2941), and 4:>1825(n = 2602) days., Results: The mean days from AF diagnosis to first ablation was 3.5 ± 3.8 years (EF > 35%: 3.5 ± 3.8 years, EF ≤ 35%: 3.4 ± 3.8 years, p = .66). In the EF > 35% group, delays in treatment (181-545 vs. 30-180, 546-1825 vs. 30-180, >1825 vs. 30-180 days) increased the risk of death with a hazard ratio (HR) of 2.02(p < .0001), 2.62(p < .0001), and 4.39(p < .0001) respectively with significant risks for HF hospitalization (HR:1.44-3.69), stroke (HR:1.11-2.14), and AF recurrence (HR:1.42-1.81). In patients with an EF ≤ 35%, treatment delays also significantly increased risk of death (HR 2.07-3.77) with similar trends in HF hospitalization (HR:1.63-1.09) and AF recurrence (HR:0.79-1.24)., Conclusion: Delays in catheter ablation for AF resulted in increased all-cause mortality in all patients with differential impact observed on HF hospitalization, stroke, and AF recurrence risks by baseline EF. These data favor earlier use of ablation for AF in patients with and without structural heart disease., (© 2023 Wiley Periodicals LLC.)

Background: Oral sotalol is a class III antiarrhythmic commonly used for the maintenance of sinus rhythm in patients with atrial fibrillation (AF). Recently, the Food and Drug Administration (FDA) approved the use of IV sotalol loading, based primarily on modeling data for the infusion. We aimed to describe a protocol and experience with IV sotalol loading for elective treatment of adult patients with AF and atrial flutter (AFL)., Methods: We present our institutional protocol and retrospective review of initial patients treated with IV sotalol for AF/AFL at the University of Utah Hospital between September 2020 and April 2021., Results: Eleven patients received IV sotalol for initial loading or dose escalation. All patients were male, aged 56-88 years (median 69). Mean QT interval (QTc) intervals increased from baseline (mean 384 ms) immediately after infusion of IV sotalol (mean change 42ms), but no patient required discontinuation of the medication. Six patients were discharged after 1 night; 4 patients were discharged after 2 nights; and 1 patient was discharged after 4 nights. Nine patients underwent electrical cardioversion prior to discharge (2 prior to load; 7 post-load on the day of discharge). There were no adverse events during the infusion or within 6 months of discharge. Persistence of therapy was 73% (8 of 11) at mean 9.9 weeks to follow up, with no discontinuations for adverse effects., Conclusions: We employed a streamlined protocol that was successfully implemented to facilitate the use of IV sotalol loading for atrial arrhythmias. Our initial experience suggests feasibility, safety, and tolerability while reducing hospitalization duration. Additional data are needed to augment this experience as IV sotalol use is broadened across different patient populations., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Computational models have made it possible to study the effect of fibrosis and scar on atrial fibrillation (AF) and plan future personalized treatments. Here, we study the effect of area available for fibrillatory waves to sustain AF. Then we use it to plan for AF ablation to improve procedural outcomes. CARPentry was used to create patient-specific models to determine the association between the size of residual contiguous areas available for AF wavefronts to propagate and sustain AF [fibrillatory area (FA)] after ablation with procedural outcomes. The FA was quantified in a novel manner accounting for gaps in ablation lines. We selected 30 persistent AF patients with known ablation outcomes. We divided the atrial surface into five areas based on ablation scar pattern and anatomical landmarks and calculated the FAs. We validated the models based on clinical outcomes and suggested future ablation lines that minimize the FAs and terminate rotor activities in simulations. We also simulated the effects of three common antiarrhythmic drugs. In the patient-specific models, the predicted arrhythmias matched the clinical outcomes in 25 of 30 patients (accuracy 83.33%). The average largest FA (FA max ) in the recurrence group was 8517 ± 1444 vs. 6772 ± 1531 mm 2 in the no recurrence group (p < 0.004). The final FAs after adding the suggested ablation lines in the AF recurrence group reduced the average FA max from 8517 ± 1444 to 6168 ± 1358 mm 2 (p < 0.001) and stopped the sustained rotor activity. Simulations also correctly anticipated the effect of antiarrhythmic drugs in 5 out of 6 patients who used drug therapy post unsuccessful ablation (accuracy 83.33%). Sizes of FAs available for AF wavefronts to propagate are important determinants for ablation outcomes. FA size in combination with computational simulations can be used to direct ablation in persistent AF to minimize the critical mass required to sustain recurrent AF., (© 2022. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Background: The role of fiber orientation on a global chamber level in sustaining atrial fibrillation (AF) is unknown. The goal of this study was to correlate the fiber direction derived from Diffusion Tensor Imaging (DTI) with AF inducibility., Methods: Transgenic goats with cardiac-specific overexpression of constitutively active TGF-β1 (n = 14) underwent AF inducibility testing by rapid pacing in the left atrium. We chose a minimum of 10 minutes of sustained AF as a cut-off for AF inducibility. Explanted hearts underwent DTI to determine the fiber direction. Using tractography data, we clustered, visualized, and quantified the fiber helix angles in 8 different regions of the left atrial wall using two reference vectors defined based on anatomical landmarks., Results: Sustained AF was induced in 7 out of 14 goats. The mean helix fiber angles in 7 out of 8 selected regions were statistically different (P-Value < 0.05) in the AF inducible group. The average fractional anisotropy (FA) and the mean diffusivity (MD) were similar in the two groups with FA of 0.32±0.08 and MD of 8.54±1.72 mm2/s in the non-inducible group and FA of 0.31±0.05 (P-value = 0.90) and MD of 8.68±1.60 mm2/s (P-value = 0.88) in the inducible group., Conclusions: DTI based fiber direction shows significant variability across subjects with a significant difference between animals that are AF inducible versus animals that are not inducible. Fiber direction might be contributing to the initiation and sustaining of AF, and its role needs to be investigated further., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kamali et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: We aimed to measure patient-reported outcomes (PROs) and costs associated with same-day discharge (SDD) for atrial fibrillation (AF) ablation and vascular closure device implantation in clinical practice., Methods: PROs were prospectively measured in 50 AF ablation patients, comparing complete vascular device closure (n = 25) versus manual compression hemostasis (n = 25). Health-system costs for SDD patients receiving vascular device closure were compared to matched controls with one-night stays who did not receive any closure device., Results: Prospectively enrolled patients receiving vascular device closure for AF ablation had a mean age of 65 years, 17% were female, with a mean CHA 2 DS 2 -VASc score of 3. The mean number of venous sheaths was higher among patients receiving vascular device closure (3.8 vs. 3.1, p < 0.001), and there was one case of rebleeding in a patient receiving a vascular closure device (no other complications). Same-day discharge rates (76% vs. 8.3%, p < 0.001), patient satisfaction with bedrest time (8.5 vs. 6, p = 0.004) and with pain (8 vs. 5.1, p = 0.009) were significantly better among patients receiving vascular closure. In matched analyses of health-system costs, patients with vascular closure had mean age 66, 32% were female, and the mean CHA 2 DS 2 -VASc score was 2 (p = NS vs. controls). SDD with vascular closure was associated with the significantly lower facility, pharmacy, and disposable costs, but higher implant costs. Overall costs for ablation were not significantly different (mean difference 1.10%, 95% confidence interval [CI] -3.03 to 5.42)., Conclusions: Vascular closure for AF ablation improves patient experience in routine care. The use of vascular closure and SDD after AF ablation reduces several components of healthcare system costs, without an overall increase., (© 2022 Wiley Periodicals LLC.)

Introduction: Esophageal injury is rare but potentially a devastating complication of atrial fibrillation (AF) ablation. The goal here was to provide insight into the short-term natural history of esophageal thermal injury (ETI) after radiofrequency catheter ablation (RFCA) for AFby esophagogastroduodenoscopy (EGD)., Methods: We screened patients who underwent RFCA for AF and EGD based on esophageal late gadolinium enhancement (LGE) in postablation magnetic resonance imaging. Patients with ETI diagnosed with EGD were included. We defined severity of ETI according to Kansas City classification: type 1: erythema; type 2: ulcers (2a: superficial; 2b deep); type 3 perforation (3a: perforation; 3b: perforation with atrioesophageal fistula [AEF]). Repeated EGD was performed within 1-14 days after the last EGD if recommended and possible until any certain healing signs (visible reduction in size without deepening of ETI or complete resolution) were observed., Results: ETI was observed in 62 of 378 patients who underwent EGD after RFCA. Out of these 62 patients with ETI, 21% (13) were type 1, 50% (31) were type 2a and 29% (18) were type 2b at the initial EGD. All esophageal lesions, but one type 2b lesion that developed into an AEF, showed signs of healing in repeated EGD studies within 14 days after the procedure. The one type 2b lesion developing into an AEF showed an increase in size and ulcer deepening in repeat EGD 8 days after the procedure., Conclusion: We found that all ETI which did not progress to AEF presented healing signs within 14 days after the procedure and that worsening ETI might be an early signal for developing esophageal perforation., (© 2022 Wiley Periodicals LLC.)

Background: Esophageal thermal injury (ETI) is a known and potentially serious complication of catheter ablation for atrial fibrillation. We intended to evaluate the distance between the esophagus and the left atrium posterior wall (LAPW) and its association with esophageal thermal injury., Methods: A retrospective analysis of 73 patients who underwent esophagogastroduodenoscopy (EGD) after LA radiofrequency catheter ablation for symptomatic atrial fibrillation and pre-ablation magnetic resonance imaging (MRI) was used to identify the minimum distance between the inner lumen of the esophagus and the ablated atrial endocardium (pre-ablation atrial esophageal distance; pre-AED) and occurrence of ETI. Parameters of ablation index (AI, Visitag Surpoint) were collected in 30 patients from the CARTO3 system and compared with assess if ablation strategies and AI further impacted risk of ETI., Results: Pre-AED was significantly larger in patients without ETI than those with ETI (5.23 ± 0.96 mm vs. 4.31 ± 0.75 mm, p < .001). Pre-AED showed high accuracy for predicting ETI with the best cutoff value of 4.37 mm. AI was statistically comparable between Visitag lesion markers with and without associated esophageal late gadolinium enhancement (LGE) detected by postablation MRI in the low-power long-duration ablation group (LPLD, 25-40 W for 10-30 s, 393.16 [308.62-408.86] vs. 406.58 [364.38-451.22], p = .16) and high-power short-duration group (HPSD, 50 W for 5-10 s, 336.14 [299.66-380.11] vs. 330.54 [286.21-384.71], p = .53), respectively., Conclusion: Measuring the distance between the LA and the esophagus in pre-ablation LGE-MRI could be helpful in predicting ETI after LAPW ablation., (© 2022 Wiley Periodicals LLC.)

Purpose: Exfoliation syndrome, a systemic disorder with ocular manifestations, is associated with lysyl oxidase-like gene variants. Along with transforming growth factor beta-1, lysyl oxidase-like 1 is a key enzyme in stabilizing extracellular matrix and remodelling collagen/elastin. Given the role that transforming growth factor beta-1, lysyl oxidase-like gene variants and fibrosis play in atrial fibrillation, an association with exfoliation syndrome was investigated., Methods: An exfoliation syndrome cohort of 2803 patients and an atrial fibrillation cohort of 43 694 patients aged 60-90 years at disease onset were identified using the Utah Population Database (1996-2015). Conditional logistic regression was used to estimate risk of atrial fibrillation in exfoliation syndrome patients and risk of exfoliation syndrome in atrial fibrillation patients compared with respective 5:1 sex- and age-matched control cohorts. Kaplan-Meier curves were examined to assess survival in atrial fibrillation patients by exfoliation syndrome status., Results: Exfoliation syndrome patients had a 21% greater risk (95% CI 1.06-1.37; p < 0.0001) of atrial fibrillation. This was more pronounced in exfoliation syndrome patients with no hypertension history, who exhibited a 52% increased atrial fibrillation risk (95% CI 1.27-1.82; p < 0.0001). Atrial fibrillation patients exhibited a 20% increased risk of exfoliation syndrome (95% CI 1.07-1.35; p = 0.003), while atrial fibrillation patients with no hypertension had a 72% higher exfoliation risk (95% CI 1.45-2.03; p < 0.0001). Atrial fibrillation patients with exfoliation syndrome had a higher estimated probability of survival (alive at study end or at last follow-up) compared with patients with no exfoliation history (p < 0.0001, log-rank test)., Conclusions: Exfoliation syndrome patients were at a statistically significant increased risk of atrial fibrillation. Similarly, atrial fibrillation patients were at a statistically significant higher risk of exfoliation, particularly when hypertension history was absent., (© 2021 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Class 1C antiarrhythmic drugs (AAD) have been associated with harm in patients treated for ventricular arrhythmias with a prior myocardial infarction. Consensus guidelines have advocated that these drugs not be used in patients with stable coronary artery disease (CAD). However, long-term data are lacking to know if unique risks exist when these drugs are used for atrial fibrillation (AF) in patients with CAD without a prior myocardial infarction., Methods: In 24,315 patients treated with the initiation of AADs, two populations were evaluated: (1) propensity-matched AF patients with CAD were created based upon AAD class (flecainide, n = 1,114, vs class-3 AAD, n = 1,114) and (2) AF patients who had undergone a percutaneous coronary intervention or coronary artery bypass graft (flecainide, n = 150, and class-3 AAD, n = 1,453). Outcomes at 3 years for mortality, heart failure (HF) hospitalization, ventricular tachycardia (VT), and MACE were compared between the groups., Results: At 3 years, mortality (9.1% vs 19.3%, P < .0001), HF hospitalization (12.5% vs 18.3%, P < .0001), MACE (22.9% vs 36.6%, P < .0001), and VT (5.8% vs 8.5%, P = .02) rates were significantly lower in the flecainide group for population 1. In population 2, adverse event rates were also lower, although not significantly, in the flecainide compared to the class-3 AAD group for mortality (20.9% vs 25.8%, P = .26), HF hospitalization (24.5% vs 26.1%, P = .73), VT (10.9% vs 14.7%, P = .28) and MACE (44.5% vs 49.5%, P = .32)., Conclusions: Flecainide in select patients with stable CAD for AF has a favorable safety profile compared to class-3 AADs. These data suggest the need for prospective trials of flecainide in AF patients with CAD to determine if the current guideline-recommended exclusion is warranted., Competing Interests: Declaration of Competing Interest Benjamin Steinberg receives support from the National Heart, Lung, And Blood Institute of the National Institutes of Health (#K23HL143156), and reports research support from Abbott, Boston Scientific, and Janssen; and consulting to Janssen, AltaThera, Merit Medical, and Bayer; and speaking for NACCME (funded by Sanofi). Ravi Ranjan is supported by NIH R01 HL142913. Ravi Fanjan also has or has had recent research grants from Biosense Webster and Abbott and is a consultant to Abbott and Biosense Webster. John Day has consulted with Abbott Medical and Boston Scientific. T. Jared Bunch MD has received research grants: Boehringer Ingelheim, Boston Scientific, Altathera. All others report no conflicts of interest relevant to this study., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: postoperative atrial fibrillation (POAF) is a common cardiac surgery complication that is associated with increased complications and negative outcomes, but the association between presurgical atrial conduction abnormalities and POAF has not been investigated clinically during premature atrial S1S2 stimulation. This clinical study sought to examine whether intraoperative premature atrial stimulation reveals increased areas of slowed and/or blocked conduction in patients that develop POAF., Methods: High-density intraoperative epicardial left atrial mapping was conducted in 20 cardiac surgery patients with no prior history of atrial fibrillation (AF). In 20 patients, 6 (30%) developed POAF. A flexible-array of 240-electrodes was placed on the posterior left atrial wall in between the pulmonary veins. Activation maps were generated for sinus and premature atrial S1S2 stimulated beats. The area of conduction block (CB), conduction delay (CD) and the combination of both (CDCB) for conduction velocity < 0.1, 0.1 ≤ x < 0.2 and < 0.2 m/s, respectively were quantified., Results: For a premature atrial S2 beat with shortest cycle length captured, conduction velocity maps revealed a significantly higher area for CD (13.19 ± 6.59 versus 6.06 ± 4.22 mm 2 , p = 0.028) and CDCB (17.36 ± 8.75 versus 7.41 ± 6.39 mm 2 , p = 0.034), and a trend toward a larger area for CB (4.17 ± 3.66 versus 1.34 ± 2.86 mm 2 , p = 0.063) in patients who developed POAF in comparison to those that remained in the sinus. Sinus and S1 paced beats did not show substantial differences in abnormal conduction areas between patients with and without POAF., Conclusion: In comparison to sinus and S1 beats, premature atrial S2 beats accentuate conduction abnormalities in the posterior left atrial wall of cardiac surgery patients that developed POAF., Competing Interests: Declaration of Competing Interest RR is a consultant for Abbott, Medtronic, and Biosense Webster. All other authors have no relevant financial or non-financial interests to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Slow conduction areas and conduction block in the atria are considered pro-arrhythmic conditions. Studies examining the size and distribution of slow conduction regions in the context of persistent atrial fibrillation (AF) may help to develop improved therapeutic strategies for patients with AF. In this work, we studied the differences of size and number in slow conduction areas between control and persistent AF goats and the influence of propagation direction on the development of these pathological conduction areas. Epicardial atrial electrical activations from the left atrial roof were optically mapped with physiological pacing cycle lengths and for the shortest captured cycle lengths. The recordings were converted to local activation times and conduction velocity measures. Regions with slow conduction velocity (less than [Formula: see text]) were identified. The size of the connected regions and the number of non-connected regions were counted for propagation from different orthogonal directions. We found that regions of slow conduction significantly increases in our 15 persistent AF goat recordings in response to premature stimulation (24.4±4.3% increase to 36.6±4.4%, p < 0.001). This increase is driven by an increase of size from (3.70±0.89[mm2] to 6.36±0.91[mm2], p = 0.014) for already existing regions and not by generation of new slow conduction regions (11.6±1.8 vs. 13±1.9, p = 0.242). In 12 control goat recordings, no increase from baseline pacing to premature pacing was found. Similarly, size of the slow conduction areas and the count did not change significantly in control animals., Competing Interests: The authors have declared that no competing interests exist.

Objectives: This study sought to evaluate atrial fibrillation (AF) ablation outcomes based on scar patterns and contiguous area available for AF wavefronts to propagate., Background: The relevance of ablation scar pattern acting as a barrier for electrical propagation in recurrence after catheter ablation for persistent AF is unknown., Methods: Three-month post-ablation atrial cardiac magnetic resonance was used to determine post-ablation scar. The left atrium (LA) was divided into 5 areas based on anatomical landmarks and scar patterns. The length of gaps in scar on the area boundaries was used to calculate fibrillatory areas (FAs) by adding the weighted contribution of adjacent areas. Cylindrical as well as patient-specific computational models were used to further confirm findings., Results: A total of 75 patients that underwent an initial ablation for AF with 2 years of follow-up were included. The average maximum FA was 7,896 ± 1,988 mm 2 in patients with recurrence (n = 40) and 6,559 ± 1,784 mm 2 in patients without recurrence (n = 35) (p < 0.008). After redo ablation in 19 patients with recurrence, average maximum FA was 7,807 ± 1,392 mm 2 in 9 patients with recurrence and 5,030 ± 1,765 mm 2 in 10 without recurrence (p < 0.007). LA volume and total scar were not significant predictors of recurrence after the first ablation. In the cylindrical model, AF self-terminated after reducing the FAs. In the patient-specific models, simulation matched the clinical outcomes with larger FAs associated with post-ablation arrhythmia recurrences., Conclusions: This data provides mechanistic insights into AF recurrence, suggesting that post-ablation scar pattern dividing the atria into smaller regions is an important and better predictor than LA volume and total scar, with improved long-term outcomes in persistent AF., Competing Interests: Funding Support and Author Disclosures Dr. Ranjan is currently supported by NIH grant R01HL142913; is a consultant to Medtronic, Biosense Webster and Abbott; has recently received research grants from Medtronic, St. Jude, and Biosense Webster; and has served as the principal investigator for research grants from Biosense Webster and Abbott to the University of Utah. Dr. Bunch has received research grant support from Boehringer Ingelheim, Boston Scientific, and Altathera. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Atrial fibrillation (AF) significantly reduces health-related quality of life (HRQoL), previously measured in clinical trials using patient-reported outcomes (PROs). We examined AF PROs in clinical practice and their association with subsequent clinical management., Methods: The Utah My Evaluation (mEVAL) program collects the Toronto AF Symptom Severity Scale (AFSS) in AF outpatients at the University of Utah. Baseline factors associated with worse AF symptom score (range 0-35, higher is worse) were identified in univariate and multivariable analyses. Secondary outcomes included AF burden and AF healthcare utilization. We also compared subsequent clinical management at 6 months between patients with better versus worse AF HRQoL., Results: Overall, 1338 patients completed the AFSS symptom score, which varied by sex (mean 7.26 for males vs. 10.27 for females; p < .001), age (<65, 9.73; 65-74, 7.66; ≥75, 7.58; p < .001), heart failure (9.39 with HF vs. 7.67 without; p < .001), and prior ablation (7.28 with prior ablation vs. 8.84; p < .001). In multivariable analysis, younger age (mean difference 2.92 for <65 vs. ≥75; p < .001), female sex (mean difference 2.57; p < .001), pulmonary disease (mean difference 1.88; p < .001), and depression (mean difference 2.46; p < .001) were associated with higher scores. At 6-months, worse baseline symptom score was associated with the use of rhythm control (37.1% vs. 24.5%; p < .001). Similar cofactors and results were associated with increased AF burden and health care utilization scores., Conclusions: AF PROs in clinical practice identify highly-symptomatic patients, corroborating findings in more controlled, clinical trials. Increased AFSS score correlates with more aggressive clinical management, supporting the utility of disease-specific PROs guiding clinical practice., (© 2020 Wiley Periodicals LLC.)

Introduction: Late gadolinium enhancement (LGE) cardiac magnetic resonance imaging (MRI) can be used to detect postablation atrial scar (PAAS) but its reproducibility and reliability in clinical scans across different magnetic flux densities and scar detection methods are unknown., Methods: Patients (n = 45) having undergone two consecutive MRIs (3 months apart) on 3T and 1.5T scanners were studied. We compared PAAS detection reproducibility using four methods of thresholding: simple thresholding, Otsu thresholding, 3.3 standard deviations (SD) above blood pool (BP) mean intensity, and image intensity ratio (IIR). We performed a texture study by dividing the left atrial wall intensity histogram into deciles and evaluated the correlation of the same decile of the two scans as well as to a randomized distribution of intensities, quantified using Dice Similarity Coefficient (DSC)., Results: The choice of scanner did not significantly affect the reproducibility. The scar detection performed by Otsu thresholding (DSC of 71.26 ± 8.34) resulted in a better correlation of the two scans compared with the methods of 3.3 SD above BP mean intensity (DSC of 57.78 ± 21.2, p < .001) and IIR above 1.61 (DSC of 45.76 ± 29.55, p <.001). Texture analysis showed that correlation only for voxels with intensities in deciles above the 70th percentile of wall intensity histogram was better than random distribution (p < .001)., Conclusions: Our results demonstrate that clinical LGE-MRI can be reliably used for visualizing PAAS across different magnetic flux densities if the threshold is greater than 70th percentile of the wall intensity distribution. Also, atrial wall-based thresholding is better than BP-based thresholding for reproducible PAAS detection., (© 2020 Wiley Periodicals LLC.)

Postoperative atrial fibrillation (POAF) after cardiac surgery remains a highly prevalent and costly condition that negatively impacts patient quality of life and survival. Numerous retrospective studies, meta-analysis, and review papers have been reported identifying POAF risk based on patients' risk factors and clinical biomarkers. In this narrative review, the authors report significant variations among selected pre- and perioperative biomarkers used to predict POAF incidence in patients without a history of atrial fibrillation (AF). POAF prediction based on B-type natriuretic peptide, N-terminal pro B-type natriuretic peptide, C-reactive protein, interleukin-6, creatinine, and plasminogen activator inhibitor-1 differs significantly among different studies, thereby limiting their clinical utility to predict POAF risk with high accuracy. Conversely, soluble vascular endothelial cells adhesion molecule-1, soluble CD40 ligand, Galectin-3, and aldosterone show promise for better POAF prediction. However, the current datasets for these selected biomarkers are not of sufficient size to validate the broad clinical application specifically for patients with no prior history of AF., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aims: Incorporating patient-reported outcomes (PROs) into routine care of atrial fibrillation (AF) enables direct integration of symptoms, function, and health-related quality of life (HRQoL) into practice. We report our initial experience with a system-wide PRO initiative among AF patients., Methods and Results: All patients with AF in our practice undergo PRO assessment with the Toronto AF Severity Scale (AFSS), and generic PROs, prior to electrophysiology clinic visits. We describe the implementation, feasibility, and results of clinic-based, electronic AF PRO collection, and compare AF-specific and generic HRQoL assessments. From October 2016 to February 2019, 1586 unique AF patients initiated 2379 PRO assessments, 2145 of which had all PRO measures completed (90%). The median completion time for all PRO measures per visit was 7.3 min (1st, 3rd quartiles: 6, 10). Overall, 38% of patients were female (n = 589), mean age was 68 (SD 12) years, and mean CHA2DS2-VASc score was 3.8 (SD 2.0). The mean AFSS symptom score was 8.6 (SD 6.6, 1st, 3rd quartiles: 3, 13), and the full range of values was observed (0, 35). Generic PROs of physical function, general health, and depression were impacted at the most severe quartiles of AF symptom score (P < 0.0001 for each vs. AFSS quartile)., Conclusion: Routine clinic-based, PRO collection for AF is feasible in clinical practice and patient time investment was acceptable. Disease-specific AF PROs add value to generic HRQoL instruments. Further research into the relationship between PROs, heart rhythm, and AF burden, as well as PRO-guided management, is necessary to optimize PRO utilization., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Objectives: The goal of this study was to find effective parameters that can be used in real-time that result in chronic scar verified by left atrial (LA) late gadolinium enhancement cardiac magnetic resonance (LGE-CMR)., Background: Automated annotation can be a useful tool while ablating in tagging areas that will result in scar, but the effective settings that best predict chronic scar are still unknown., Methods: Patients underwent pulmonary vein isolation using a CARTO3 mapping system with a VISITAG Module and 3-month post-ablation LGE-CMR. The electroanatomical map (EAM) was used to retrospectively tag ablated areas with 5 different parameters: catheter stability; stability duration; force over time; minimum contact force; and impedance drop. The ablation tags in EAM were projected to the 3-month post-ablation LGE-CMR. Tags were divided into 2 groups depending on if they correlated with CMR-based scar tags (STAGs) or nonscar tags (NTAGs); the effective parameters were estimated for the 2 groups at different power levels., Results: This study assessed 70 consecutive patients and 28,939 ablation tags. Ablation time and force time integral (FTI) were significantly larger in the STAG group. Mean contact force, change of catheter tip temperature, and impedance were not significantly different between STAGs and NTAGs. The minimum ablation time and FTI to make durable scar lesions were 17.6, 13.6, and 11.0 s and 226.1, 187.4, and 161.4 g at 25, 35, and 50 W, respectively., Conclusions: Minimum ablation time and FTI values are critical parameters that determine durable atrial scar creation and their minimum values vary with the ablation power setting., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Recent guidelines recommend a 3-month blanking period after atrial fibrillation (AF) ablations, which are based on clinical observation. Our goal was to quantify the timeline of the radiofrequency ablation lesion maturation using serial late gadolinium enhancement-magnetic resonance imaging (LGE-MRI) and to develop a blanking period estimate based on visible lesion maturation., Methods: Inclusion criteria targeted patients who underwent AF ablation and at least four MRI scans: at baseline before ablation, within 24 hours after (acute), between 24 hours and 90 days after (subacute), and more than 90 days after ablation (chronic). Central nonenhanced (NE) and surrounding hyperenhanced (HE) area volumes were measured and normalized to chronic lesion volume., Results: This study assessed 75 patients with 309 MRIs. The acute lesion was heterogeneous with a HE region surrounding a central NE region in LGE-MRI; the acute volume of the total (HE + NE) lesion was 2.62 ± 0.46 times larger than that of the chronic lesion. Acute T2-weighted imaging also showed a relatively large area of edema. Both NE and HE areas gradually receded over time and NE was not observed after 30 days. Larger initial NE volume was associated with a significantly greater chronic scar volume and this total lesion volume receded to equal the chronic lesion size at approximately 72.5 days (95% prediction interval: 57.4-92.2)., Conclusion: On the basis of serial MRI, atrial ablation lesions are often fully mature before the typical 90-day blanking period, which could support more timely clinical decision making for arrhythmia recurrence., (© 2020 Wiley Periodicals, Inc.)

Background: Preclinical and clinical studies have utilized periprocedural parameters to optimize cryoballoon ablation dosing, including acute time-to-isolation (TTI) of the pulmonary vein, balloon rate of freezing, balloon nadir temperature, and balloon-thawing time. This study sought to predict the Arctic Front Advance (AFA) vs Arctic Front Advance Pro (AFA Pro) ablation durations required for transmural pulmonary vein isolation at varied tissue depths., Methods: A cardiac-specific, three-dimensional computational model that incorporates structural characteristics, temperature-dependent cellular responses, and thermal-conductive properties was designed to predict the propagation of cold isotherms through tissue. The model assumed complete cryoballoon-to-pulmonary vein (PV) circumferential contact. Using known temperature thresholds of cardiac cellular electrical dormancy (at 23°C) and cellular nonviability (at -20°C), transmural time-to-isolation electrical dormancy (TTI ED ) and cellular nonviability (TTI NV ) were simulated., Results: For cardiac thickness of 0.5, 1.25, 2.0, 3.0, 4.0, and 5.0 mm, the 23°C isotherm passed transmurally in 33, 38, 46, 62, 80, and 95 seconds during cryoablation utilizing AFA and 33, 38, 46, 63, 80, and 95 seconds with AFA Pro. Using the same cardiac thicknesses, the -20°C isotherm passed transmurally in 40, 55, 78, 161, 354, and 696 seconds during cryoablation with AFA and 40, 54, 78, 160, 352, and 722 seconds with AFA Pro., Conclusion: This model predicted a minimum duration of cryoballoon ablation (TTI NV ) to obtain a transmural lesion when acute TTI of the PV was observed (TTI ED ). Consequently, the model is a useful tool for characterizing CBA dosing, which may guide future cryoablation dosing strategies., (© 2019 The Authors. Journal of Cardiovascular Electrophysiology Published by Wiley Periodicals, Inc.)

Background: Atrial fibrillation (AF) is related to numerous electrophysiological changes; however, the extent of structural and electrophysiological remodeling with long-term AF is not well characterized., Methods: Dogs (n = 6) were implanted with a neurostimulator in the right atrium (AF group). No implantation was done in the Control group (n = 3). Electroanatomical mapping was done prior to and following more than 6 months of AF. Magnetic resonance imaging was also done to assess structural remodeling. Animals were euthanized and tissue samples were acquired for histological analysis., Results: A significant increase was seen in the left atrial (LA) volume among all AF animals (22.25 ± 12.60 cm 3 vs 34.00 ± 12.23 cm 3 , P = .01). Also, mean bipolar amplitude in the LA significantly decreased from 5.96 ± 2.17 mV at baseline to 3.23 ± 1.51 mV (P < .01) after chronic AF. Those significant changes occurred in each anterior, lateral, posterior, septal, and roof regions as well. Additionally, the dominant frequency (DF) in the LA increased from 7.02 ± 0.37 Hz to 10.12 ± 0.28 Hz at chronic AF (P < .01). Moreover, the percentage of fibrosis in chronic AF animals was significantly larger than that of control animals in each location (P < .01)., Conclusions: Canine chronic AF is accompanied by a significant decrease in intracardiac bipolar amplitudes. These decreased electrogram amplitude values are still higher than traditional cut-off values used for diseased myocardial tissue. Despite these "normal" bipolar amplitudes, there is a significant increase in DF and tissue fibrosis., (© 2019 Wiley Periodicals, Inc.)

Atrial fibrillation (AF) is the most common cardiac rhythm disorder and is associated with heart failure (HF). Cardiac imaging modalities play an important role in risk assessment and managing AF. This article reviews the use of cardiac imaging for risk assessment and to optimize treatment strategy in patients with AF and HF. First, the clinical role of echocardiography, computed tomography, and cardiac magnetic resonance for risk stratification is provided. Second, the value of imaging in catheter ablation is reviewed, including preoperative assessment, optimizing patient selection for ablation, use during the ablation procedure, and postoperative scar assessment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Postoperative atrial fibrillation (POAF) is a common arrhythmia following cardiac surgery and is associated with increased health-care costs, complications, and mortality. The etiology of POAF is incompletely understood and its prediction remains suboptimal. Using data from published studies, we performed a systemic review and meta-analysis to identify preoperative clinical risk factors associated with patients at increased risk of POAF., Methods: A systematic search of PubMed, MEDLINE, and EMBASE databases was performed., Results: Twenty-four studies that reported univariate analysis results regarding POAF risk factors, published from 2001 to May 2017, were included in this meta-analysis with a total number of 36,834 subjects. Eighteen studies were performed in the United States and Europe and 16 studies were prospective cohort studies. The standardized mean difference (SMD) between POAF and non-POAF groups was significantly different (reported as [SMD: 95% confidence interval, CI]) for age (0.55: 0.47-0.63), left atrial diameter (0.45: 0.15-0.75), and left ventricular ejection fraction (0.30: 0.14-0.47). The pooled odds ratios (ORs) (reported as [OR: 95% CI]) demonstrated that heart failure (1.56: 1.31-1.96), chronic obstructive pulmonary disease (1.36: 1.13-1.64), hypertension (1.29: 1.12-1.48), and myocardial infarction (1.18: 1.05-1.34) were significant predictors of POAF incidence, while diabetes was marginally significant (1.06: 1.00-1.13)., Conclusion: The present analysis suggested that older age and history of heart failure were significant risk factors for POAF consistently whether the included studies were prospective or retrospective datasets., Competing Interests: Dr. Ravi Ranjan is partially supported by the National Heart, Lung, and Blood Institute (NHLBI) grants K23HL115084 and R56HL128674.Partial support for Dr. Nan Hu was provided by the University of Utah Study Design and Biostatistics Center (SDBC), with funding in part from the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant 5UL1TR001067–02 (formerly 8UL1TR000105 and UL1RR025764).Research reported in this publication was supported by the NHLBI to Dr. Derek J. Dosdall under award number R01HL128752.None of the listed grant support represents a conflict of interest. None of the authors have a financial interest related to the work presented in this manuscript., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Differentiating between atrial fibrillation (AF) and atrial tachycardia (AT) or atrial flutter (AFL) on surface ECG can be challenging. The same problem arises in animal models of AF, in which atrial arrhythmias are induced by pacing or pharmacological intervention with the goal of making mechanistic determinations. Some of these induced arrhythmias can be AFL or AT, even though it might appear as AF on the body-surface ECG based on irregular R-R intervals. We hypothesize that a dominant frequency (DF) analysis of the ECG can differentiate between the two distinct arrhythmias, even when it is not evident by the presence of flutter waves or beat-to-beat regularity when looking at brief recordings., Methods: Canine model (n = 15, 10 controls and 5 Persistent AF animals with >6 months of AF) was used to test the hypothesis. Atrial arrhythmia was induced by rapid atrial pacing. Five blinded observers evaluated the 3‑lead surface ECGs recorded during atrial arrhythmia and classified the rhythm as AFL/AT or AF. The 64-electrode Constellation (Boston Scientific) catheter was used to acquire left (entire group) and right (7 of 10 controls) atrial intracardiac electrograms. For the surface ECG and the intracardiac electrograms, Welch method with a hamming window and 50% overlap was used to calculate DF of two-minute segments. Mean of standard deviations of the DF values were calculated for both ECGs and intracardiac EGMs. Ground truth came from activations maps and DF analysis derived from the intracardiac electrograms recorded in the two chambers., Results: Rapid pacing induced atrial arrhythmias in all the control animals. The ECG in 8 of the 10 control cases was read as AF by at least 80% percent of observers even though the EGMs from the Constellation showed organized activation and consistent DF (STD of DF < 0.001) in all the electrodes confirming the arrhythmia as AFL in 10/10 cases. In the persistent AF group, the DF from the three lead ECGs were significantly different (Mean of STDs = 2.65 ± 0.99) whereas the DF in the control animals with AFL was consistent across all ECG channels (Mean of STDs < 0.001), and the DF in the control animals ECGs was in agreement with the DF of the intracardiac electrograms., Conclusion: Surface ECG recordings can mimic AF even when the underlying atrial arrhythmia is AFL in control canine models. DF variation of the signals from multiple surface ECG leads can help differentiate between the AF and AFL., (Copyright © 2018. Published by Elsevier Inc.)

Purpose: MRI or CT imaging can be used to identify the esophageal location prior to left atrial ablation, but the esophagus may move making the location unreliable when ablating to minimize esophageal injury. The aim of this study was to evaluate esophageal position and movement based on serial MRI imaging with the goal of identifying imaging and clinical characteristics that can predict the esophageal movement., Methods: Fifty patients undergoing 190 MRI scans were analyzed. The relative position of the esophagus in each MRI along with clinical and imaging characteristics was quantified, including the gap between the left atrium (LA) and the vertebral body (GAP), an anatomic space in which the esophagus can move., Results: A mean of 3.8 MRIs was analyzed per patient. Sixteen patients (32.0%) experienced significant lateral esophageal movement of more than 10 mm. In the significant movement group, body mass index (BMI) was higher (33.0 ± 6.5 vs 28.8 ± 5.3, p = 0.02) and the GAP was significantly larger (7.1 ± 2.5 vs 4.8 ± 5.1 mm, p = 0.04). Multivariate logistic regression analysis revealed that the GAP ≤ 4.5 mm was the only independent predictor of the esophagus not moving (odds ratio = 9.25, 95% confidence interval = 1.72 to 49.67, p = 0.0095)., Conclusions: A GAP of less than 4.5 mm between the LA and the vertebral body is associated with lack of esophageal movement (< 10 mm). This suggests that the measurement of GAP < 4.5 mm may be used to predict the esophageal location in patients undergoing atrial ablation.

Introduction: Large animal models of progressive atrial fibrosis would provide an attractive platform to study relationship between structural and electrical remodeling in atrial fibrillation (AF). Here we established a new transgenic goat model of AF with cardiac specific overexpression of TGF-β1 and investigated the changes in the cardiac structure and function leading to AF., Methods and Results: Transgenic goats with cardiac specific overexpression of constitutively active TGF-β1 were generated by somatic cell nuclear transfer. We examined myocardial tissue, ECGs, echocardiographic data, and AF susceptibility in transgenic and wild-type control goats. Transgenic goats exhibited significant increase in fibrosis and myocyte diameters in the atria compared to controls, but not in the ventricles. P-wave duration was significantly greater in transgenic animals starting at 12 months of age, but no significant chamber enlargement was detected, suggesting conduction slowing in the atria. Furthermore, this transgenic goat model exhibited a significant increase in AF vulnerability. Six of 8 transgenic goats (75%) were susceptible to AF induction and exhibited sustained AF (>2 minutes), whereas none of 6 controls displayed sustained AF (P < 0.01). Length of induced AF episodes was also significantly greater in the transgenic group compared to controls (687 ± 212.02 seconds vs. 2.50 ± 0.88 seconds, P < 0.0001), but no persistent or permanent AF was observed., Conclusion: A novel transgenic goat model with a substrate for AF was generated. In this model, cardiac overexpression of TGF-β1 led to an increase in fibrosis and myocyte size in the atria, and to progressive P-wave prolongation. We suggest that these factors underlie increased AF susceptibility., (© 2016 Wiley Periodicals, Inc.)

Purpose: Patients routinely undergo ablation for atrial fibrillation (AF) but the recurrence rate remains high. We explored in this study whether poor scar formation as seen on late-gadolinium enhancement magnetic resonance imaging (LGE-MRI) correlates with AF recurrence following ablation., Methods: We retrospectively identified 94 consecutive patients who underwent their initial ablation for AF at our institution and had pre-procedural magnetic resonance angiography (MRA) merged with left atrial (LA) anatomy in an electroanatomic mapping (EAM) system, ablated areas marked intraprocedurally in EAM, 3-month post-ablation LGE-MRI for assessment of scar, and minimum of 3-months of clinical follow-up. Ablated area was quantified retrospectively in EAM and scarred area was quantified in the 3-month post-ablation LGE-MRI., Results: With the mean follow-up of 336 days, 26 out of 94 patients had AF recurrence. Age, hypertension, and heart failure were not associated with AF recurrence, but LA size and difference between EAM ablated area and LGE-MRI scar area was associated with higher AF recurrence. For each percent higher difference between EAM ablated area and LGE-MRI scar area, there was a 7-9% higher AF recurrence (p values 0.001-0.003) depending on the multivariate analysis., Conclusions: In AF ablation, poor scar formation as seen on LGE-MRI was associated with AF recurrence. Improved mapping and ablation techniques are necessary to achieve the desired LA scar and reduce AF recurrence.

Introduction: Patients with paroxysmal atrial fibrillation (AF) often transition between sinus rhythm and AF. For AF to initiate there must be both a trigger and a substrate that facilitates reentrant activity. This trigger is often caused by a premature atrial contraction or focal activations within the atrium. We hypothesize that specific architectures of fibrosis alter local conduction to enable AF., Methods and Results: Control goats (n = 13) and goats in chronic AF (for an average of 6 months, n = 6) had a high-density electrode plaque placed on the LA appendage. Conduction patterns following a premature atrial contraction, caused by an electrical stimulation, were quantified to determine regions of conduction slowing. These regions were compared to architecture, either diffuse fibrosis or regions of obstructive fibrosis, and overall fibrosis levels as determined by histology from the mapped region. The chronic AF goats had more obstructive fibrosis than the controls (17.5 ± 8.0 fibers/mm(2) vs. 8.6 ± 3.0 fibers/mm(2)). Conduction velocity of the AF goats was significantly slowed compared to the control goats in the transverse direction (0.40 ± 0.04 m/s vs. 0.53 ± 0.15 m/s) but not in the longitudinal direction (0.70 ± 0.27 m/s vs. 0.76 ± 0.18 m/s)., Conclusions: AF-induced atrial remodeling leads to increased obstructive fibrosis and conduction velocity slowing transverse to fiber orientation following premature stimuli. The decrease in conduction velocity causes a decrease in the cardiac wavelength, and increases the likelihood of reentry and AF onset., (© 2015 Wiley Periodicals, Inc.)

Introduction: Chronic kidney disease (CKD) and atrial fibrillation (AF) often coexist. We studied the association of CKD with atrial fibrosis and the effect of AF ablation on kidney function., Methods: AF patients who had a pre- and postablation serum creatinine and who completed a late gadolinium enhancement cardiac magnetic resonance imaging (MRI; LGE-MRI) prior to ablation were included. Estimated glomerular filtration rate (eGFR) was calculated and CKD was staged using the National Kidney Foundation guidelines. Patients with eGFR <30 mL/min/1.73 m(2) were excluded. LGE-MRI was used to quantify atrial fibrosis. Patients were followed for recurrence and change in eGFR., Results: A total of 392 patients were included in the study. A total of 118 (30.2%) had CKD stage 1, 198 (50.4%) CKD stage 2, 56 (14.3%) CKD stage 3A, and 20 (5.1%) CKD stage 3B. Patients with advanced CKD were more likely to be male and to have cardiovascular disease. Atrial fibrosis was not significant different between included CKD stages: 15.8 ± 8.8%, 16.6 ± 12.1%, 17.1 ± 10.4%, and 16.5 ± 8.4% for CKD stage 1, 2, 3A, and 3B, respectively (P = 0.476). At a median of 115 days following ablation, eGFR increased significantly in CKD stage 2 (74 ± 9 to 80 ± 23; P = 0.04), 3A (53 ± 5 to 69 ± 24; P < 0.001), and 3B (40 ± 4 to 71 ± 28; P < 0.01) and decreased in CKD stage 1 (109 ± 18 to 82 ± 28; P < 0.001). Arrhythmia recurrence was associated with atrial fibrosis (hazard ratio [HR] = 1.04, P < 0.01) and persistent AF (HR = 1.5; P = 0.04) but not with CKD stage (HR = 0.98; P = 0.89)., Conclusions: Restoring sinus rhythm with ablation leads to significant improvement of renal function in patients with chronic kidney disease., (© 2014 Wiley Periodicals, Inc.)

Left atrial (LA) perfusion during disease states has been a topic of much interest, because the clinical implications and detrimental effects of lack of blood flow to the atria are numerous. In the chronic setting, changes in perfusion may lead to LA ischaemia and structural remodelling, a factor implicated in the self-perpetuation of chronic atrial fibrillation (AF). The association between AF and altered LA perfusion has been studied, but a direct causal association between perfusion changes and AF has not been established. A comprehensive literature search of Medline, Embase and Google Scholar databases was conducted from 1960 to February 2014. We systematically analysed reference lists of physiological articles and reviews for other possibly relevant studies. The aim of this review is to provide a comprehensive discussion of the AF-mediated changes in LA perfusion and the potential mechanisms underlying the alterations in coronary flow to the LA in this setting. In addition, we discuss the clinical contexts in which changes in LA perfusion may be relevant. Finally, this article highlights the need for longitudinal studies of AF that would elucidate the changes in LA perfusion resulting from chronic AF and lead to advancements in effective treatments to prevent progression of this disease., (© 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.)

Background: Three-dimensional electroanatomic mapping (EAM) is routinely used to mark ablated areas during radiofrequency ablation. We hypothesized that, in atrial fibrillation (AF) ablation, EAM overestimates scar formation in the left atrium (LA) when compared to the scar seen on late-gadolinium enhancement magnetic resonance imaging (LGE-MRI)., Methods and Results: Of the 235 patients who underwent initial ablation for AF at our institution between August 2011 and December 2012, we retrospectively identified 70 patients who had preprocedural magnetic resonance angiography merged with LA anatomy in EAM software and had a 3-month postablation LGE-MRI for assessment of scar. Ablated area was marked intraprocedurally using EAM software and quantified retrospectively. Scarred area was quantified in 3-month postablation LGE-MRI. The mean ablated area in EAM was 30.5 ± 7.5% of the LA endocardial surface and the mean scarred area in LGE-MRI was 13.9 ± 5.9% (P < 0.001). This significant difference in the ablated area marked in the EAM and scar area in the LGE-MRI was present for each of the 3 independent operators. Complete pulmonary vein (PV) encirclement representing electrical isolation was observed in 87.8% of the PVs in EAM as compared to only 37.4% in LGE-MRI (P < 0.001)., Conclusions: In AF ablation, EAM significantly overestimates the resultant scar as assessed with a follow-up LGE-MRI., (© 2014 Wiley Periodicals, Inc.)

Background: Although catheter ablation therapy for atrial fibrillation (AF) is becoming more common, results vary widely, and patient selection criteria remain poorly defined. We hypothesized that late gadolinium enhancement MRI (LGE-MRI) can identify left atrial (LA) wall structural remodeling (SRM) and stratify patients who are likely or not to benefit from ablation therapy., Methods and Results: LGE-MRI was performed on 426 consecutive patients with AF without contraindications to MRI before undergoing their first ablation procedure and on 21 non-AF control subjects. Patients were categorized by SRM stage (I-IV) based on the percentage of LA wall enhancement for correlation with procedure outcomes. Histological validation of SRM was performed comparing LGE-MRI with surgical biopsy. A total of 386 patients (91%) with adequate LGE-MRI scans were included in the study. After ablation, 123 patients (31.9%) experienced recurrent atrial arrhythmias during the 1-year follow-up. Recurrent arrhythmias (failed ablations) occurred at higher SRM stages with 28 of 133 (21.0%) in stage I, 40 of 140 (29.3%) in stage II, 24 of 71 (33.8%) in stage III, and 30 of 42 (71.4%) in stage IV. In multivariate analysis, ablation outcome was best predicted by advanced SRM stage (hazard ratio, 4.89; P<0.0001) and diabetes mellitus (hazard ratio, 1.64; P=0.036), whereas increased LA volume and persistent AF were not significant predictors. LA wall enhancement was significantly greater in patients with AF versus non-AF controls (16.6±11.2% versus 3.1±1.9%; P<0.0001). Histological evidence of remodeling from surgical biopsy specimens correlated with SRM on LGE-MRI., Conclusions: Atrial SRM is identified on LGE-MRI, and extensive LGE (≥30% LA wall enhancement) predicts poor response to catheter ablation therapy for AF.

Structural remodeling in chronic atrial fibrillation (AF) occurs over weeks to months. To study the electrophysiological, structural, and functional changes that occur in chronic AF, the selection of the best animal model is critical. AF was induced by rapid atrial pacing (50-Hz stimulation every other second) in pigs (n = 4), dogs (n = 8), and goats (n = 9). Animals underwent MRIs at baseline and 6 mo to evaluate left ventricular (LV) ejection fraction (EF). Dogs were given metoprolol (50-100 mg po bid) and digoxin (0.0625-0.125 mg po bid) to limit the ventricular response rate to <180 beats/min and to mitigate the effects of heart failure. The pacing leads in pigs became entirely encapsulated and lost the ability to excite the heart, often before the onset of sustained AF. LV EF in dogs dropped from 54 ± 11% at baseline to 33 ± 7% at 6 mo (P < 0.05), whereas LV EF in goats did not drop significantly (69 ± 8% at baseline vs. 60 ± 9% at 6 mo, P = not significant). After 6 mo of AF, fibrosis levels in dog atria and ventricles increased, whereas only atrial fibrosis levels increased in goats compared with control animals. In our experience, the pig model is not appropriate for chronic rapid atrial pacing-induced AF studies. Rate-controlled chronic AF in the dog model developed HF and LV fibrosis, whereas the goat model developed only atrial fibrosis without ventricular dysfunction and fibrosis. Both the dog and goat models are representative of segments of the patient population with chronic AF.

Background: Magnetic resonance imaging (MRI) can visualize locations of both the ablation scar on the left atrium (LA) after atrial fibrillation (AF) ablation and epicardial fat pads (FPs) containing ganglionated plexi (GP)., Methods: We investigated 60 patients who underwent pulmonary vein antrum (PVA) isolation along with LA posterior wall and septal debulking for AF. FPs around the LA surface in well-known GP areas (which were considered as the substitution of GP areas around the LA) were segmented from the dark-blood MRI. Then the FP and the ablation scar image visualized by late gadolinium enhancement (LGE)-MRI on the LA were merged together. Overlapping areas of FP and the ablation scar image were considered as the ablated FP areas containing GP. Patients underwent 24-hour Holter monitoring after ablation for the analysis of heart rate variability., Results: Ablated FP area was significantly wider in patients without AF recurrence than those in patients with recurrence (5.6 ± 3.1 cm(2) vs 4.2 ± 2.7 cm(2) , P = 0.03). The mean values of both percentage of differences greater than 50 ms in the RR intervals (pRR > 50) and standard deviation of RR intervals over the entire analyzed period (SDNN), which were obtained from 24-hour Holter monitoring 1-day post-AF ablation, were significantly lower in patients without recurrence than those in patients with recurrence (5.8 ± 6.0% vs 14.0 ± 10.1%; P = 0.0005, 78.7 ± 32.4 ms vs 109.2 ± 43.5 ms; P = 0.005). There was a significant negative correlation between SDNN and the percentage of ablated FP area (Y = -1.3168X + 118.96, R(2) = 0.1576, P = 0.003)., Conclusion: Extensively ablating LA covering GP areas along with PVA isolation enhanced the denervation of autonomic nerve system and seemed to improve procedural outcome in patients with AF., (©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.)

Introduction: Sinus node dysfunction (SND) commonly manifests with atrial arrhythmias alternating with sinus pauses and sinus bradycardia. The underlying process is thought to be because of atrial fibrosis. We assessed the value of atrial fibrosis, quantified using late gadolinium enhanced-MRI (LGE-MRI), in predicting significant SND requiring pacemaker implant., Methods: Three hundred forty-four patients with atrial fibrillation (AF) presenting for catheter ablation underwent LGE-MRI. Left atrial (LA) fibrosis was quantified in all patients and right atrial (RA) fibrosis in 134 patients. All patients underwent catheter ablation with pulmonary vein isolation with posterior wall and septal debulking. Patients were followed prospectively for 329 ± 245 days. Ambulatory monitoring was instituted every 3 months. Symptomatic pauses and bradycardia were treated with pacemaker implantation per published guidelines., Results: The average patient age was 65 ± 12 years. The average wall fibrosis was 16.7 ± 11.1% in the LA, and 5.3 ± 6.4% in the RA. RA fibrosis was correlated with LA fibrosis (R(2) = 0.26; P < 0.01). Patients were divided into 4 stages of LA fibrosis (Utah I: <5%, Utah II: 5-20%, Utah III: 20-35%, Utah IV: >35%). Twenty-two patients (mean atrial fibrosis, 23.9%) required pacemaker implantation during follow-up. Univariate and multivariate analysis identified LA fibrosis stage (OR, 2.2) as a significant predictor for pacemaker implantation with an area under the curve of 0.704., Conclusions: In patients with AF presenting for catheter ablation, LGE-MRI quantification of atrial fibrosis demonstrates preferential LA involvement. Significant atrial fibrosis is associated with clinically significant SND requiring pacemaker implantation., (© 2011 Wiley Periodicals, Inc.)

Background: Ablation has become an important tool in treating atrial fibrillation and ventricular tachycardia, yet the recurrence rates remain high. It is well established that ablation lines can be discontinuous and that conduction through the gaps in ablation lines can be affected by tissue heating. In this study, we looked at the effect of tissue conductivity and propagation of electric wave fronts across ablation lines with gaps, using both simulations and an animal model., Methods and Results: For the simulations, we implemented a 2-dimensional bidomain model of the cardiac syncytium, simulating ablation lines with gaps of varying lengths, conductivity, and orientation. For the animal model, transmural ablation lines with a gap were created in 7 mongrel dogs. The gap length was progressively decreased until there was conduction block. The ablation line with a gap was then imaged using MRI and was correlated with histology. With normal conductivity in the gap and the ablation line oriented parallel to the fiber direction, the simulation predicted that the maximum gap length that exhibited conduction block was 1.4 mm. As the conductivity was decreased, the maximum gap length with conduction block increased substantially, that is, with a conductivity of 67% of normal, the maximum gap length with conduction block increased to 4 mm. In the canine studies, the maximum gap length that displayed conduction block acutely as measured by gross pathology correlated well (R(2) of 0.81) with that measured by MRI., Conclusions: Conduction block can occur across discontinuous ablation lines. Moreover, with recovery of conductivity over time, ablation lines with large gaps exhibiting acute conduction block may recover propagation in the gap over time, allowing recurrences of arrhythmias. The ability to see gaps acutely using MRI will allow for targeting these sites for ablation.

Both post-contrast myocardial T1 and extracellular volume (ECV) measurements have been associated with diffuse interstitial fibrosis. The cardiovascular magnetic resonance (CMR) field is migrating towards ECV, because it is largely insensitive to confounders that affect post-contrast myocardial T1 . Despite the theoretical advantages of myocardial ECV over post-contrast myocardial T1 , systematic experimental studies comparing the two measurements are largely lacking. We sought to measure the temporal changes in post-contrast myocardial T1 and ECV in an established canine model with chronic atrial fibrillation. Seventeen mongrel dogs, implanted with a pacemaker to induce chronic atrial fibrillation via rapid atrial pacing, were scanned multiple times for a total of 46 CMR scans at 3T. These dogs with different disease durations (0-22 months) were part of a separate longitudinal study aimed at studying the relationship between AF and pathophysiology. In each animal, we measured native and post-contrast T1 values and hematocrit. Temporal changes in post-contrast myocardial T1 and ECV, as well as other CMR parameters, were modeled with linear mixed effect models to account for repeated measurements over disease duration. In 17 animals, post-contrast myocardial T1 decreased significantly from 872 to 698 ms (p < 0.001), which corresponds to a 24.9% relative reduction. In contrast, ECV increased from 21.0 to 22.0% (p = 0.38), which corresponds to only a 4.5% relative increase. To partially investigate this discrepancy, we quantified collagen volume fraction (CVF) in post-mortem heart tissues of six canines sacrificed at different disease durations (0-22 months). CVF quantified by histology increased from 0.9 to 1.9% (p = 0.56), which agrees better with ECV than with post-contrast myocardial T1 . This study shows that post-contrast myocardial T1 and ECV may disagree in a longitudinal canine study. A more comprehensive study, including histologic, cardiac, and renal functional analyses, is warranted to test rigorously which CMR parameter (ECV or post-contrast myocardial T1 ) agrees better with CVF.

Aims: Incorporating patient-reported outcomes (PROs) into routine care of atrial fibrillation (AF) enables direct integration of symptoms, function, and health-related quality of life (HRQoL) into practice. We report our initial experience with a system-wide PRO initiative among AF patients.Methods and Results: All patients with AF in our practice undergo PRO assessment with the Toronto AF Severity Scale (AFSS), and generic PROs, prior to electrophysiology clinic visits. We describe the implementation, feasibility, and results of clinic-based, electronic AF PRO collection, and compare AF-specific and generic HRQoL assessments. From October 2016 to February 2019, 1586 unique AF patients initiated 2379 PRO assessments, 2145 of which had all PRO measures completed (90%). The median completion time for all PRO measures per visit was 7.3 min (1st, 3rd quartiles: 6, 10). Overall, 38% of patients were female (n = 589), mean age was 68 (SD 12) years, and mean CHA2DS2-VASc score was 3.8 (SD 2.0). The mean AFSS symptom score was 8.6 (SD 6.6, 1st, 3rd quartiles: 3, 13), and the full range of values was observed (0, 35). Generic PROs of physical function, general health, and depression were impacted at the most severe quartiles of AF symptom score (P < 0.0001 for each vs. AFSS quartile).Conclusion: Routine clinic-based, PRO collection for AF is feasible in clinical practice and patient time investment was acceptable. Disease-specific AF PROs add value to generic HRQoL instruments. Further research into the relationship between PROs, heart rhythm, and AF burden, as well as PRO-guided management, is necessary to optimize PRO utilization. [ABSTRACT FROM AUTHOR]

Both post-contrast myocardial T1 and extracellular volume (ECV) measurements have been associated with diffuse interstitial fibrosis. The cardiovascular magnetic resonance (CMR) field is migrating towards ECV, because it is largely insensitive to confounders that affect post-contrast myocardial T1. Despite the theoretical advantages of myocardial ECV over post-contrast myocardial T1, systematic experimental studies comparing the two measurements are largely lacking. We sought to measure the temporal changes in post-contrast myocardial T1 and ECV in an established canine model with chronic atrial fibrillation. Seventeen mongrel dogs, implanted with a pacemaker to induce chronic atrial fibrillation via rapid atrial pacing, were scanned multiple times for a total of 46 CMR scans at 3T. These dogs with different disease durations (0-22 months) were part of a separate longitudinal study aimed at studying the relationship between AF and pathophysiology. In each animal, we measured native and post-contrast T1 values and hematocrit. Temporal changes in post-contrast myocardial T1 and ECV, as well as other CMR parameters, were modeled with linear mixed effect models to account for repeated measurements over disease duration. In 17 animals, post-contrast myocardial T1 decreased significantly from 872 to 698 ms ( p < 0.001), which corresponds to a 24.9% relative reduction. In contrast, ECV increased from 21.0 to 22.0% ( p = 0.38), which corresponds to only a 4.5% relative increase. To partially investigate this discrepancy, we quantified collagen volume fraction (CVF) in post-mortem heart tissues of six canines sacrificed at different disease durations (0-22 months). CVF quantified by histology increased from 0.9 to 1.9% ( p = 0.56), which agrees better with ECV than with post-contrast myocardial T1. This study shows that post-contrast myocardial T1 and ECV may disagree in a longitudinal canine study. A more comprehensive study, including histologic, cardiac, and renal functional analyses, is warranted to test rigorously which CMR parameter (ECV or post-contrast myocardial T1) agrees better with CVF. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]