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Arrhythmogenic Fibrotic Atrial Cardiomyopathy (FAM) and Atrial Fibrillation: Pathophysiology, Diagnosis, Treatment and Consequences for Prevention of Ischemic Stroke

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Cardiology".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 19300

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Dr. Amir Jadidi

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Arrhythmia Division, Cardiology Clinics, University Heart-Center Freiburg-Bad Krozingen, University of Freiburg, Freiburg, Germany
Interests: left atrial arrhythmogenic fibrotic cardiomyopathy (FAM); voltage mapping; mapping of atrial fibrillation sources; gadolinium enhanced MRI; 12-lead-ECG; p-wave markers of LA arrhythmogenic cardiomyopathy; risk prediction for future AF, ischemic stroke, heart failure and sudden cardiac death; atrial fibrillation; ischemic stroke; sudden cardiac death

Special Issue Information

Dear Colleagues,

Recently, important insights have been gained that emphasize the importance of fibrotic atrial myopathy (FAM) in atrial fibrillation (AF), left atrial thrombogenesis, and ischemic stroke.
Focal and re-entrant arrhythmia sources that trigger and maintain AF preferentially develop at atrial sites with increased fibrosis and altered myocardial structure with slow electrical conduction. While in the majority of patients with paroxysmal AF the arrhythmogenic fibrotic sites are limited to the pulmonary veins and their antra, in a substantial portion of patients with persistent AF the arrhythmogenic substrate extends to the atrial body. Not surprisingly, recurrence rates following catheter ablation of AF are relatively high in these patients when pulmonary vein isolation is performed without additional ablation of the atrial arrhythmogenic fibrotic substrate and AF triggers.
Moreover, recent data suggest that FAM plays an important role in identification of patients at risk for future AF, left atrial thrombogenesis, or stroke; FAM is associated with loss of atrial contractile function, leading to increased risk for left-atrial thrombogenesis and ischemic stroke. FAM can be diagnosed by detailed analysis of the P-wave in high-resolution digital 12-lead-ECG, three-dimensional (3D)-Gadolinium-enhanced MRI, atrial flow velocity MRI, analysis of inter-/intra-atrial contraction delay by echocardiography or MRI, and analysis of atrial mechanical function by strain analysis in transthoracic and transesophageal echocardiography or MRI.

This Special Issue of the Journal of Clinical Medicine will focus on the pathophysiology, diagnosis, and treatment of FAM in the context of AF and stroke. Potential topics include, but are not limited to:

the pathophysiological factors that are associated with development of FAM and AF;
current non-invasive (ECG, echocardiography, MRI, PET, biomarkers, clinical risk-scores, etc.) and invasive diagnostic tools (endocardial mapping of atrial low-voltage areas and slow conduction areas) to identify FAM;
treatment options that may allow for “reverse atrial remodeling” and a reduction of FAM;
novel AF mapping and ablation strategies for persistent AF that address the patient-specific arrhythmogenic atrial substrate/trigger sites in FAM (beyond pulmonary vein isolation) to improve outcomes; and
the role of FAM as a risk factor for left atrial thrombogenesis, ischemic stroke, and cardiovascular mortality in patients with or without known atrial fibrillation.

Dr. Amir Jadidi
Guest Editor

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Keywords

left atrial fibrosis
left atrial arrhythmogenic fibrotic cardiomyopathy (FAM)
low-voltage mapping
arrhythmogenic substrate
mapping of atrial fibrillation
gadolinium-enhanced MRI
atrial flow and strain analysis (echocardiography, MRI)
12-lead-ECG
P-wave markers of LA arrhythmogenic cardiomyopathy
risk prediction
atrial fibrillation
ischemic stroke
cardiovascular mortality.

Published Papers (8 papers)

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Research

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11 pages, 1459 KiB

Open AccessArticle

Echocardiographic and Electrocardiographic Determinants of Atrial Cardiomyopathy Identify Patients with Atrial Fibrillation at Risk for Left Atrial Thrombogenesis

by Taiyuan Huang, Schurr Patrick, Louisa Katharina Mayer, Björn Müller-Edenborn, Martin Eichenlaub, Martin Allgeier, Jürgen Allgeier, Heiko Lehrmann, Christoph Ahlgrim, Marius Bohnen, Simon Schoechlin, Dietmar Trenk, Nikolaus Jander, Franz Josef Neumann, Thomas Arentz and Amir Jadidi

J. Clin. Med. 2022, 11(5), 1332; https://doi.org/10.3390/jcm11051332 - 28 Feb 2022

Cited by 4 | Viewed by 1855

Abstract

Objective: Atrial cardiomyopathy (ACM) is associated with development of AF, left atrial (LA) thrombogenesis, and stroke. Diagnosis of ACM is feasible using both echocardiographic LA strain imaging and measurement of the amplified p-wave duration (APWD) in digital 12-lead-ECG. We sought to determine the thresholds of LA global longitudinal strain (LA-GLS) and APWD that identify patients with AF at risk for LA appendage (LAA) thrombogenesis. Methods: One hundred and twenty-eight patients with a history of AF were included. Left atrial appendage maximal flow velocity (LAA-Vel, in TEE), LA-GLS (TTE), and APWD (digital 12-lead-ECG) were measured in all patients. ROC analysis was performed for each method to determine the thresholds for LA-GLS and the APWD, enabling diagnosis of patients with LAA-thrombus. Results: Significant differences in LA-GLS were found during both rhythms (SR and AF) between the thrombus group and control group: LA-GLS in SR: 14.3 ± 7.4% vs. 24.6 ± 9.0%, p < 0.001 and in AF: 11.4 ± 4.2% vs. 16.1 ± 5.0%, p = 0.045. ROC analysis revealed a threshold of 17.45% for the entire cohort (AUC 0.82, sensitivity: 84.6%, specificity: 63.6%, Negative Predictive Value (NPV): 94.3%) with additional rhythm-specific thresholds: 19.1% in SR and 13.9% in AF, and a threshold of 165 ms for APWD (AUC 0.90, sensitivity: 88.5%, specificity: 75.5%, NPV: 96.2%) as optimal discriminators of LAA-thrombus. Moreover, both LA-GLS and APWD correlated well with the established contractile LA-parameter LAA-Vel in TEE (r = 0.39, p < 0.001 and r = −0.39, p < 0.001, respectively). Conclusion: LA-GLS and APWD are valuable diagnostic predictors of left atrial thrombogenesis in patients with AF. Full article

(This article belongs to the Special Issue Arrhythmogenic Fibrotic Atrial Cardiomyopathy (FAM) and Atrial Fibrillation: Pathophysiology, Diagnosis, Treatment and Consequences for Prevention of Ischemic Stroke)

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14 pages, 2231 KiB

Open AccessArticle

Ablation of Left Atrial Tachycardia following Catheter Ablation of Atrial Fibrillation: 12-Month Success Rates

by Armin Luik, Kerstin Schmidt, Annika Haas, Laura Unger, Panagiotis Tzamalis and Bernd Brüggenjürgen

J. Clin. Med. 2022, 11(4), 1047; https://doi.org/10.3390/jcm11041047 - 17 Feb 2022

Cited by 4 | Viewed by 1732

Abstract

The treatment of atrial tachycardia following catheter ablation of atrial fibrillation is often challenging. Electrophysiological studies using high-resolution 3D mapping systems have contributed significantly to their understanding, and new ablation approaches have shown high rates of acute terminations with low recurrences for the clinical AT. However, patient populations are very heterogeneous, and long-term data of the freedom from any atrial tachycardia or any arrhythmia are still sparse. To evaluate long-term success, a unified patient population and predefined ablation strategies are preferred. In this study, we present 12-month success and mean 30 month follow-up data of catheter ablation of left atrial tachycardia. All 35 patients had a history of pulmonary vein isolation (PVI), 71% of which had a previous substrate modification. A total of 54 ATs, with a mean cycle length 297 ± 86 ms, 31 macro-reentries, and 4 localized reentries, were targeted. The ablation strategy to be used was given by the study protocol, depending on the type of reentry and the number of critical isthmuses. All available ablation strategies were included: standard (anatomical) lines, individual lines, critical isthmuses, and focal ablation. All ATs were terminated by ablation. A total of 91% terminated upon the first ablation strategy. Freedom from any AT after 12 months was 82%, and from any arrhythmia, it was 77%. The multi-procedure success after 30 months was 65% for any AT and 55% for any arrhythmia. In conclusion, individual ablation strategies based on the reentry mechanism and the number of critical isthmuses seems promising and demonstrates a high long-term clinical success. Tachycardia comprising a single critical isthmus can be ablated by critical isthmus ablation only. These patients present with the highest 12-month and long-term success rates. Full article

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10 pages, 1564 KiB

Open AccessArticle

Left Atrium Assessment by Speckle Tracking Echocardiography in Cryptogenic Stroke: Seeking Silent Atrial Fibrillation

by Mireia Ble, Begoña Benito, Elisa Cuadrado-Godia, Sílvia Pérez-Fernández, Miquel Gómez, Aleksandra Mas-Stachurska, Helena Tizón-Marcos, Lluis Molina, Julio Martí-Almor and Mercè Cladellas

J. Clin. Med. 2021, 10(16), 3501; https://doi.org/10.3390/jcm10163501 - 09 Aug 2021

Cited by 11 | Viewed by 2267

Abstract

Silent atrial fibrillation (AF) may be the cause of some cryptogenic strokes (CrS). The aim of the study was to analyse atrial size and function by speckle tracking echocardiography in CrS patients to detect atrial disease. Patients admitted to the hospital due to CrS were included prospectively. Echocardiogram analysis included left atrial ejection fraction (LAEF) and atrial strain. Insertable cardiac monitor was implanted, and AF was defined as an episode of ≥1 min in the first year after stroke. Left atrial enlargement was defined as indexed volume > 34 mL/m². Seventy-five consecutive patients were included, aged 76 ± 9 years (arterial hypertension 75%). AF was diagnosed in 49% of cases. The AF group had higher atrial volume and worse atrial function: peak atrial longitudinal strain (PALs) 19.6 ± 5.7% vs. 29.5 ± 7.2%, peak atrial contraction strain (PACs) 8.9 ± 3.9% vs. 16.5 ± 6%, LAEF 46.8 ± 11.5% vs. 60.6 ± 5.2%; p < 0.001. AF was diagnosed in 20 of 53 patients with non-enlarged atrium, and in 18 of them, atrial dysfunction was present. The multivariate logistic regression analysis demonstrated an independent association between detection of AF and atrial volume, LAEF, and strain. Cut-off values were obtained: LAEF < 55%, PALs < 21.4%, and PACs < 12.9%. In conclusion, speckle tracking echocardiography in CrS patients improves silent atrial disease diagnosis, with or without atrial enlargement. Full article

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10 pages, 859 KiB

Open AccessArticle

Role of Different Antithrombotic Regimens after Percutaneous Left Atrial Appendage Occlusion: A Large Single Center Experience

by Patrizio Mazzone, Alessandra Laricchia, Giuseppe D’Angelo, Giulio Falasconi, Luigi Pannone, Luca Rosario Limite, David Zweiker, Damiano Regazzoli, Andrea Radinovic, Alessandra Marzi, Eustachio Agricola, Luigia Brugliera, Antonio Colombo, Paolo Della Bella and Matteo Montorfano

J. Clin. Med. 2021, 10(9), 1959; https://doi.org/10.3390/jcm10091959 - 02 May 2021

Cited by 9 | Viewed by 1840

Abstract

Background: Optimal antithrombotic therapy after left atrial appendage (LAA) occlusion is still not clear. The aim of this study was to investigate the role of different antithrombotic regimens after the procedure. Methods and Results: We retrospectively analyzed data of 260 patients who underwent LAA occlusion and divided them into four groups according to therapy at discharge: dual antiplatelet therapy (group A, 71.5%); oral anticoagulants (group B, 19%); “minimal” antithrombotic therapy (single antiplatelet agent or without any antithrombotic therapy; group C, 4.5%) and other therapeutic regimens (such as a combination of antiplatelets and anticoagulants; group D, 4.5%). We analyzed baseline characteristics, procedural data, and clinical and transesophageal follow-up for each group. The incidence of adverse events was low in the whole population and had a similar distribution among groups. The majority of bleeding events was registered during the first 3 months after the procedure (34 out of 46, 70%). Ischemic events (2%), as well as silent left atrial thrombosis, were rare and not significantly higher in the population discharged with “minimal” antithrombotic therapy. Conclusion: Our experience seems to suggest that LAA occlusion was associated with a low incidence of adverse events, regardless of antithrombotic therapy. A “minimal” drug regimen may be feasible without losing efficacy on embolic prevention for patients with high bleeding risk. Full article

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18 pages, 4686 KiB

Open AccessArticle

Non-Invasive and Quantitative Estimation of Left Atrial Fibrosis Based on P Waves of the 12-Lead ECG—A Large-Scale Computational Study Covering Anatomical Variability

by Claudia Nagel, Giorgio Luongo, Luca Azzolin, Steffen Schuler, Olaf Dössel and Axel Loewe

J. Clin. Med. 2021, 10(8), 1797; https://doi.org/10.3390/jcm10081797 - 20 Apr 2021

Cited by 21 | Viewed by 3705

Abstract

The arrhythmogenesis of atrial fibrillation is associated with the presence of fibrotic atrial tissue. Not only fibrosis but also physiological anatomical variability of the atria and the thorax reflect in altered morphology of the P wave in the 12-lead electrocardiogram (ECG). Distinguishing between the effects on the P wave induced by local atrial substrate changes and those caused by healthy anatomical variations is important to gauge the potential of the 12-lead ECG as a non-invasive and cost-effective tool for the early detection of fibrotic atrial cardiomyopathy to stratify atrial fibrillation propensity. In this work, we realized 54,000 combinations of different atria and thorax geometries from statistical shape models capturing anatomical variability in the general population. For each atrial model, 10 different volume fractions (0–45%) were defined as fibrotic. Electrophysiological simulations in sinus rhythm were conducted for each model combination and the respective 12-lead ECGs were computed. P wave features (duration, amplitude, dispersion, terminal force in V1) were extracted and compared between the healthy and the diseased model cohorts. All investigated feature values systematically in- or decreased with the left atrial volume fraction covered by fibrotic tissue, however value ranges overlapped between the healthy and the diseased cohort. Using all extracted P wave features as input values, the amount of the fibrotic left atrial volume fraction was estimated by a neural network with an absolute root mean square error of 8.78%. Our simulation results suggest that although all investigated P wave features highly vary for different anatomical properties, the combination of these features can contribute to non-invasively estimate the volume fraction of atrial fibrosis using ECG-based machine learning approaches. Full article

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14 pages, 1030 KiB

Open AccessArticle

High-Sensitivity C-Reactive Protein is a Predictor of Subsequent Atrial High-Rate Episodes in Patients with Pacemakers and Preserved Ejection Fraction

by Min-Tsun Liao, Chun-Kai Chen, Ting-Tse Lin, Li-Ying Cheng, Hung-Wen Ting and Yen-Bin Liu

J. Clin. Med. 2020, 9(11), 3677; https://doi.org/10.3390/jcm9113677 - 16 Nov 2020

Cited by 2 | Viewed by 1617

Abstract

Atrial fibrillation (AF) is associated with morbidity and mortality. Modern pacemakers can detect atrial high-rate episodes (AHREs) as a surrogate for AF. It remains controversial whether inflammation is a cause or a consequence of AF. This study investigated whether the inflammatory biomarker high-sensitivity C-reactive protein (hs-CRP) can predict subsequent AHREs. This study gathered prospective data from patients with pacemakers and a left ventricle EF ≥ 50% between 2015 and 2019. The hs-CRP and other cardiac biomarkers at baseline and device-detected AHREs, defined as atrial rate ≥ 180 bpm and duration ≥ 6 min, were determined. Cox regression analysis was used to estimate the independent predictors for AHREs. A total of 171 consecutive patients were included. During the median follow-up of 614 days, 66 patients (39%) developed subsequent AHREs. In the univariate Cox regression analysis, sick sinus syndrome (p = 0.005), prior AF (p < 0.001), mitral A velocity (p = 0.008), and hs-CRP (p = 0.013) showed significant association with the increased risk of AHREs. In the multivariate Cox regression model, hs-CRP (HR = 1.121, 95% confidence interval = 1.015–1.238, p = 0.024) retained its significance. Our results suggest that elevated hs-CRP could predict subsequent AHREs and that inflammation could play a role in AF pathogenesis in patients with preserved EF. Full article

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13 pages, 1328 KiB

Open AccessArticle

Sinus Rhythm Conduction Properties across Bachmann’s Bundle: Impact of Underlying Heart Disease and Atrial Fibrillation

by Christophe P. Teuwen, Lisette J.M.E. van der Does, Charles Kik, Elisabeth M.J.P. Mouws, Eva A.H. Lanters, Paul Knops, Yannick J.H.J. Taverne, Ad J.J.C. Bogers and Natasja M.S. de Groot

J. Clin. Med. 2020, 9(6), 1875; https://doi.org/10.3390/jcm9061875 - 16 Jun 2020

Cited by 2 | Viewed by 2017

Abstract

Valvular heart disease (VHD) is a common risk factor for atrial fibrillation (AF). Conduction abnormalities (CA) during sinus rhythm (SR) across Bachmann’s bundle (BB) are associated with AF development. The study goal is to compare electrophysiological characteristics across BB during SR between patients with ischemic (IHD) and/or VHD either with or without ischemic heart disease ((I)VHD), with/without AF history using high-resolution intraoperative epicardial mapping. In total, 304 patients (IHD: n = 193, (I)VHD: n = 111) were mapped; 40 patients (13%) had a history of AF. In 116 patients (38%) there was a mid-entry site with a trend towards more mid-entry sites in patients with (I)VHD vs. IHD (p = 0.061), whereas patients with AF had significant more mid-entry sites than without AF (p = 0.007). CA were present in 251 (95%) patients without AF compared to 39 (98%) with AF. The amount of CA was comparable in patients with IHD and (I)VHD (p > 0.05); AF history was positively associated with the amount of CA (p < 0.05). Receiver operating characteristic (ROC) curve showed 85.0% sensitivity and 86.4% specificity for cut-off values of CA lines of respectively ≤ 6 mm and ≥ 26 mm. Patients without a mid-entry site or long CA lines (≥ 12 mm) were unlikely to have AF (sensitivity 90%, p = 0.002). There are no significant differences in entry-sites of wavefronts and long lines of CA between patients with IHD compared to (I)VHD. However, patients with AF have more wavefronts entering in the middle of BB and a higher incidence of long CA lines compared to patients without a history of AF. Moreover, in case of absence of a mid-entry site or long line of CA, patients most likely have no history of AF. Full article

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Review

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14 pages, 2772 KiB

Open AccessReview

Imaging Techniques for the Study of Fibrosis in Atrial Fibrillation Ablation: From Molecular Mechanisms to Therapeutical Perspectives

by Francesco De Sensi, Diego Penela, David Soto-Iglesias, Antonio Berruezo and Ugo Limbruno

J. Clin. Med. 2021, 10(11), 2277; https://doi.org/10.3390/jcm10112277 - 24 May 2021

Cited by 9 | Viewed by 2988

Abstract

Atrial fibrillation (AF) is the most prevalent form of cardiac arrhythmia. It is often related to diverse pathological conditions affecting the atria and leading to remodeling processes including collagen accumulation, fatty infiltration, and amyloid deposition. All these events generate atrial fibrosis, which contribute to beget AF. In this scenario, cardiac imaging appears as a promising noninvasive tool for monitoring the presence and degree of LA fibrosis and remodeling. The aim of this review is to comprehensively examine the bench mechanisms of atrial fibrosis moving, then to describe the principal imaging techniques that characterize it, such as cardiac magnetic resonance (CMR) and multidetector cardiac computed tomography (MDCT), in order to tailor atrial fibrillation ablation to each individual. Full article

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Arrhythmogenic Fibrotic Atrial Cardiomyopathy (FAM) and Atrial Fibrillation: Pathophysiology, Diagnosis, Treatment and Consequences for Prevention of Ischemic Stroke

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