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  • Review Article
  • Published:

Structural remodeling in atrial fibrillation

Nature Clinical Practice Cardiovascular Medicine volume 5, pages 782–796 (2008)Cite this article

Abstract

Atrial fibrillation occurs and maintains itself in the context of a morphologically and functionally altered atrial substrate that can be induced by stressors such as underlying diseases (cardiac or noncardiac) or aging. The resultant structural remodeling is a slow process that progressively affects myocytes and the myocardial interstitium, and takes place from as early as the first days of atrial tachyarrhythmia. The left atrium, and particularly its posterior wall, is the location where remodeling is concentrated to the greatest extent. The mechanisms that underlie the remodeling process in atrial fibrillation have not yet been completely elucidated, although experimental and clinical investigations have indicated a number of signaling systems, inflammation, oxidative stress, atrial stretching and ischemia as factors involved in the cascade of events that leads to atrial fibrillation. The aim of this Review is to provide a comprehensive overview of the morphological changes that characterize the fibrillating atrial myocardium at histological and ultrastructural levels, and the established and hypothetical pathogenetic mechanisms involved in structural remodeling. This article also highlights the emerging therapies being developed to prevent progression of atrial fibrillation.

Key Points

  • Atrial fibrillation (AF) develops and persists in the context of an altered atrial myocardial environment; these alterations are termed 'structural remodeling' and embrace myocyte and interstitial changes

  • Early myocyte changes most likely represent adaptive responses to external stressors, whereas interstitial and late myocyte changes lead to irreversible damage that favors AF maintenance

  • A number of factors, such as the tachyarrhythmia itself, aging, signaling systems, inflammation, oxidative stress, atrial stretching and ischemia, have been indicated as key elements of a self-perpetuating positive feedback mechanism in AF

  • Traditional pharmacological treatments for AF are often ineffective in controlling atrial rhythm, probably because of progressively worsening structural remodeling

  • A challenging potential therapeutic approach to AF could involve the use of drugs that block the vicious cycle of initiation and persistence of AF and thus impede the progression of structural remodeling

  • Catheter ablation is a nonpharmacological treatment for AF that aims to isolate the atrial areas that are most subject to structural remodeling; destruction of myocardial tissue in these areas interrupts the re-entrant circuits that cause AF

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Figure 1: Myocardial histopathology of the left atrial posterior wall in a patient affected by atrial fibrillation and mitral valve disease.
Figure 2: Myocardial ultrastructure of the left atrial posterior wall in a patient affected by atrial fibrillation and mitral valve disease.
Figure 3: The main pathogenetic mechanisms involved in atrial structural remodeling.

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Acknowledgements

The authors are indebted to Professor Emilio Macchi, University of Parma, Parma, Italy, for his valuable suggestions. We would also like to express our gratitude to Ms Emilia Corradini for her competent technical assistance.

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Authors and Affiliations

  1. D Corradi is a Cardiovascular Pathologist and R Maestri is a Biologist in the Department of Pathology and Laboratory Medicine, Pathology Section, University of Parma, Parma.,

    Domenico Corradi & Roberta Maestri

  2. S Callegari is a Cardiologist in the Division of Cardiology, Fidenza Hospital, Fidenza, Parma.,

    Sergio Callegari

  3. S Benussi is a Cardiac Surgeon and O Alfieri is Professor of Cardiac Surgery and Head of the Cardiac Surgery Unit in the Department of Cardiology at San Raffaele University Hospital, Milan, Italy.,

    Stefano Benussi & Ottavio Alfieri

Authors
  1. Domenico Corradi
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  2. Sergio Callegari
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  3. Roberta Maestri
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  4. Stefano Benussi
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  5. Ottavio Alfieri
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Corresponding author

Correspondence to Domenico Corradi.

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Competing interests

Stefano Benussi is consultant for Estech Inc. and for Atricure Inc. and has received lecture fees from St Jude Medical Inc., Medtronic Inc., Cryocath Inc., Edwards-Lifesciences Inc.

The other authors declared no competing interests.

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Corradi, D., Callegari, S., Maestri, R. et al. Structural remodeling in atrial fibrillation. Nat Rev Cardiol 5, 782–796 (2008). https://doi.org/10.1038/ncpcardio1370

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