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Life
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Mechanisms of Atrial Fibrillation
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Mechanisms of Atrial Fibrillation

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Cell Biology and Tissue Engineering".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 11462

Special Issue Editor

Prof. Dr. Patrick Lugenbiel

E-Mail Website
Guest Editor
Medizinische Klinik, Heidelberg University, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
Interests: electrophysiology; VT-Ablation; cardiac stereotactic body radiation therapie; atrial fibrillation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Atrial fibrillation is still the most common arrhythmia and affects millions of patients worldwide. Ectopic activity of pulmonary veins is the best studied cause of induction of atrial fibrillation. Electrical disturbances due to structural or electrical remodeling leads to an easier induction and supports the maintenance of the arrhythmia. Transcriptional changes of atrial ion channels or impaired calcium homeostasis play a key role in the chronification process and the development of persistent atrial fibrillation.

This Research Topic welcomes basic, translational, clinical, and applied research that improves our understanding of atrial fibrillation. Potential areas of interest may include, but are not limited to:

  • Ion channel remodeling and calcium homeostasis
  • Translational research
  • Atrial fibrosis and the effect on electric conduction velocity
  • Intracellular signaling and regulation of gene transcription

We welcome the submission of different article types to this collection, especially reviews and original research papers. For a complete list of article types that can be considered in this Special Issue.

Dr. Patrick Lugenbiel
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Life is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • atrial fibrillation
  • ion channel
  • electrical remodeling
  • structural remodeling
  • arrhythmia

Published Papers (6 papers)

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Research

Jump to: Review

14 pages, 2876 KiB  
Article
Neurohumoral Markers of Cardiac Autonomic Denervation after Surgical Ablation of Long-Standing Persistent Atrial Fibrillation
by Alexey Evtushenko, Vladimir Evtushenko, Anna Gusakova, Tatiana Suslova, Yulia Varlamova, Konstantin Zavadovskiy, Denis Lebedev, Anton Kutikhin, Elena Pavlyukova and Sergey Mamchur
Life 2023, 13(6), 1340; https://doi.org/10.3390/life13061340 - 07 Jun 2023
Viewed by 984
Abstract
Although the autonomic nervous system has an evident impact on cardiac electrophysiology and radiofrequency ablation (RFA) is the conventional technique for treating persistent atrial fibrillation, the specific effects of RFA have been insufficiently studied to date. Here, we investigated whether RFA affects neurohumoral [...] Read more.
Although the autonomic nervous system has an evident impact on cardiac electrophysiology and radiofrequency ablation (RFA) is the conventional technique for treating persistent atrial fibrillation, the specific effects of RFA have been insufficiently studied to date. Here, we investigated whether RFA affects neurohumoral transmitter levels and myocardial 123I-metaiodobenzylguanidine (123I-MIBG) uptake. To perform this task, we compared two groups of patients with acquired valvular heart disease: patients who had undergone surgical AF ablation and patients with sinus rhythm. The decrease in norepinephrine (NE) level in the coronary sinus had a direct association with the heart-to-mediastinum ratio (p = 0.02) and a negative correlation with 123I-MIBG uptake defects (p = 0.01). The NE level decreased significantly after the main surgery, both in patients with AF (p = 0.0098) and sinus rhythm (p = 0.0039). Furthermore, the intraoperative difference between the norepinephrine levels in the ascending aorta and coronary sinus (ΔNE) of –400 pg/mL was determined as a cut-off value to evaluate RFA efficacy, as denervation failed in all patients with ΔNE < –400 pg/mL. Hence, ΔNE can be utilized to predict the efficacy of the “MAZE-IV” procedure and to assess the risk of AF recurrence after RFA. Full article
(This article belongs to the Special Issue Mechanisms of Atrial Fibrillation)
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10 pages, 1175 KiB  
Communication
Female “Paradox” in Atrial Fibrillation—Role of Left Truncation Due to Competing Risks
by Tomoki Nakamizo, Munechika Misumi, Tetsuya Takahashi, Satoshi Kurisu, Masayasu Matsumoto and Akira Tsujino
Life 2023, 13(5), 1132; https://doi.org/10.3390/life13051132 - 05 May 2023
Viewed by 1002
Abstract
Female sex in patients with atrial fibrillation (AF) is a controversial and paradoxical risk factor for stroke—controversial because it increases the risk of stroke only among older women of some ethnicities and paradoxical because it appears to contradict male predominance in cardiovascular diseases. [...] Read more.
Female sex in patients with atrial fibrillation (AF) is a controversial and paradoxical risk factor for stroke—controversial because it increases the risk of stroke only among older women of some ethnicities and paradoxical because it appears to contradict male predominance in cardiovascular diseases. However, the underlying mechanism remains unclear. We conducted simulations to examine the hypothesis that this sex difference is generated non-causally through left truncation due to competing risks (CR) such as coronary artery diseases, which occur more frequently among men than among women and share common unobserved causes with stroke. We modeled the hazards of stroke and CR with correlated heterogeneous risk. We assumed that some people died of CR before AF diagnosis and calculated the hazard ratio of female sex in the left-truncated AF population. In this situation, female sex became a risk factor for stroke in the absence of causal roles. The hazard ratio was attenuated in young populations without left truncation and in populations with low CR and high stroke incidence, which is consistent with real-world observations. This study demonstrated that spurious risk factors can be identified through left truncation due to correlated CR. Female sex in patients with AF may be a paradoxical risk factor for stroke. Full article
(This article belongs to the Special Issue Mechanisms of Atrial Fibrillation)
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11 pages, 395 KiB  
Article
Extensive Posterior Wall Isolation on Top of Pulmonary Vein Isolation Guided by Ablation Index in Persistent Atrial Fibrillation Ablation
by Francesco Sabatino, Domenico Oriente, Fabrizio Fortunato, Antonio Cascino, Giuliano Ferrara, Giuseppe Sgarito and Sergio Conti
Life 2023, 13(3), 761; https://doi.org/10.3390/life13030761 - 11 Mar 2023
Cited by 1 | Viewed by 1574
Abstract
Background: Durable pulmonary vein isolation (PVI) is recommended for symptomatic paroxysmal atrial fibrillation (AF) treatment, but it has been demonstrated that it may not be enough to treat persistent AF (Pe-AF). Therefore, posterior wall isolation (PWI) is among the strategies adopted on top [...] Read more.
Background: Durable pulmonary vein isolation (PVI) is recommended for symptomatic paroxysmal atrial fibrillation (AF) treatment, but it has been demonstrated that it may not be enough to treat persistent AF (Pe-AF). Therefore, posterior wall isolation (PWI) is among the strategies adopted on top of PVI to treat Pe-AF patients. However, PWI using contiguous and optimized radiofrequency lesions remains challenging, and few studies have evaluated the impact of the Ablation Index (AI) on the efficacy of PWI. Moreover, previous papers did not evaluate arrhythmia recurrences using continuous monitoring. Methods: This is a prospective, observational, single-center study on patients affected by Pe-AF undergoing treated PVI plus AI-guided PWI. Procedures were performed using the CARTO mapping system, SmartTouch SF ablation catheter, and PentaRay multipolar mapping catheter. The AI settings were 500–550 for the anterior PV aspect and roofline, while the settings were 450–500 for the posterior PV aspect, bottom line, and/or PW lesions. All patients received an implantable loop recorder (ILR). All patients underwent clinical evaluation in the outpatient clinic at 1, 3, 6, 12, 18, and 24 months. A standard 12-lead ECG was performed at each visit, and device data from the ILR were reviewed to assess for arrhythmia recurrence. Results: Between January 2021 and December 2021, forty-one consecutive patients underwent PVI plus PWI guided by AI at our center and were prospectively enrolled in the study. PVI was achieved in all patients, first-pass roofline block was obtained in 82.9% of the patients, and first-pass block of the bottom line was achieved in 36.5% of the patients. In 39% of the patients, PWI was not performed with a “box-only” lesion set, but with scattered lesions across the PW to achieve PWI. AI on the anterior aspect of the left PVs was 528 ± 22, while on the posterior aspect of the left PVs, it was 474 ± 18; on the anterior aspect of the right PVs, it was 532 ± 27, while on the posterior aspect of the right PVs, it was 477 ± 16; on the PW, AI was 468 ± 19. No acute complications occurred at the end of the procedure. After the blanking period, 70.7% of the patients reported no arrhythmia recurrence during the 12-month follow-up period. Conclusions: In patients with Pe-AF undergoing catheter ablation, PWI guided by AI seems to be an effective and feasible strategy in addition to standard PVI. Full article
(This article belongs to the Special Issue Mechanisms of Atrial Fibrillation)
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Review

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12 pages, 1629 KiB  
Review
Reviewing Atrial Fibrillation Pathophysiology from a Network Medicine Perspective: The Relevance of Structural Remodeling, Inflammation, and the Immune System
by Ivis Levy Fernandes Martins, Flávia Valéria dos Santos Almeida, Karyne Pollo de Souza, Fernanda Carla Ferreira de Brito, Gabriel Dias Rodrigues and Christianne Bretas Vieira Scaramello
Life 2023, 13(6), 1364; https://doi.org/10.3390/life13061364 - 10 Jun 2023
Cited by 1 | Viewed by 1451
Abstract
Atrial fibrillation (AF) is the most common type of sustained arrhythmia. The numerous gaps concerning the knowledge of its mechanism make improving clinical management difficult. As omics technologies allow more comprehensive insight into biology and disease at a molecular level, bioinformatics encompasses valuable [...] Read more.
Atrial fibrillation (AF) is the most common type of sustained arrhythmia. The numerous gaps concerning the knowledge of its mechanism make improving clinical management difficult. As omics technologies allow more comprehensive insight into biology and disease at a molecular level, bioinformatics encompasses valuable tools for studying systems biology, as well as combining and modeling multi-omics data and networks. Network medicine is a subarea of network biology where disease traits are considered perturbations within the interactome. With this approach, potential disease drivers can be revealed, and the effect of drugs, novel or repurposed, used alone or in combination, may be studied. Thus, this work aims to review AF pathology from a network medicine perspective, helping researchers to comprehend the disease more deeply. Essential concepts involved in network medicine are highlighted, and specific research applying network medicine to study AF is discussed. Additionally, data integration through literature mining and bioinformatics tools, with network building, is exemplified. Together, all of the data show the substantial role of structural remodeling, the immune system, and inflammation in this disease etiology. Despite this, there are still gaps to be filled about AF. Full article
(This article belongs to the Special Issue Mechanisms of Atrial Fibrillation)
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18 pages, 2321 KiB  
Review
Mechanisms of Atrial Fibrillation: How Our Knowledge Affects Clinical Practice
by Georgios Leventopoulos, Rafail Koros, Christoforos Travlos, Angelos Perperis, Panagiotis Chronopoulos, Evropi Tsoni, Eleni-Evangelia Koufou, Athanasios Papageorgiou, Anastasios Apostolos, Panagiotis Kaouris, Periklis Davlouros and Grigorios Tsigkas
Life 2023, 13(6), 1260; https://doi.org/10.3390/life13061260 - 25 May 2023
Cited by 5 | Viewed by 2990
Abstract
Atrial fibrillation (AF) is a very common arrhythmia that mainly affects older individuals. The mechanism of atrial fibrillation is complex and is related to the pathogenesis of trigger activation and the perpetuation of arrhythmia. The pulmonary veins in the left atrium arei confirm [...] Read more.
Atrial fibrillation (AF) is a very common arrhythmia that mainly affects older individuals. The mechanism of atrial fibrillation is complex and is related to the pathogenesis of trigger activation and the perpetuation of arrhythmia. The pulmonary veins in the left atrium arei confirm that onfirm the most common triggers due to their distinct anatomical and electrophysiological properties. As a result, their electrical isolation by ablation is the cornerstone of invasive AF treatment. Multiple factors and comorbidities affect the atrial tissue and lead to myocardial stretch. Several neurohormonal and structural changes occur, leading to inflammation and oxidative stress and, consequently, a fibrotic substrate created by myofibroblasts, which encourages AF perpetuation. Several mechanisms are implemented into daily clinical practice in both interventions in and the medical treatment of atrial fibrillation. Full article
(This article belongs to the Special Issue Mechanisms of Atrial Fibrillation)
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11 pages, 976 KiB  
Review
The Autonomic Coumel Triangle: A New Way to Define the Fascinating Relationship between Atrial Fibrillation and the Autonomic Nervous System
by Marco Rebecchi, Francesca Fanisio, Fabio Rizzi, Alessandro Politano, Ermenegildo De Ruvo, Cinzia Crescenzi, Germana Panattoni, Marianna Squeglia, Annamaria Martino, Stefano Sasso, Paolo Golia, Giulia Pugliese, Sofia Del Gigante, Domenico Giamundo, Pietro Desimone, Domenico Grieco, Lucia De Luca, Ignazio Giordano, Francesco Barillà, Marco Alfonso Perrone, Leonardo Calò and Ferdinando Iellamoadd Show full author list remove Hide full author list
Life 2023, 13(5), 1139; https://doi.org/10.3390/life13051139 - 08 May 2023
Cited by 4 | Viewed by 2645
Abstract
Arrhythmogenic substrate, modulating factors, and triggering factors (the so-called Coumel’s triangle concept) play a primary role in atrial fibrillation (AF) pathophysiology. Several years have elapsed since Coumel and co-workers advanced the concept of the relevance of autonomic nervous system (ANS) influences on atrial [...] Read more.
Arrhythmogenic substrate, modulating factors, and triggering factors (the so-called Coumel’s triangle concept) play a primary role in atrial fibrillation (AF) pathophysiology. Several years have elapsed since Coumel and co-workers advanced the concept of the relevance of autonomic nervous system (ANS) influences on atrial cells’ electrophysiological characteristics. The ANS is not only associated with cardiac rhythm regulation but also exerts an important role in the triggering and maintenance of atrial fibrillation. This review aims to describe in detail the autonomic mechanisms involved in the pathophysiology of atrial fibrillation (AF), starting from the hypothesis of an “Autonomic Coumel Triangle” that stems from the condition of the fundamental role played by the ANS in all phases of the pathophysiology of AF. In this article, we provide updated information on the biomolecular mechanisms of the ANS role in Coumel’s triangle, with the molecular pathways of cardiac autonomic neurotransmission, both adrenergic and cholinergic, and the interplay between the ANS and cardiomyocytes’ action potential. The heterogeneity of the clinical spectrum of the ANS and AF, with the ANS playing a relevant role in situations that may promote the initiation and maintenance of AF, is highlighted. We also report on drug, biological, and gene therapy as well as interventional therapy. On the basis of the evidence reviewed, we propose that one should speak of an “Autonomic Coumel’s Triangle” instead of simply “Coumel’s Triangle”. Full article
(This article belongs to the Special Issue Mechanisms of Atrial Fibrillation)
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