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FOCUS ISSUE: ATRIAL FIBRILLATION: STATE-OF-THE-ART PAPER

Atrial Fibrosis: Mechanisms and Clinical Relevance in Atrial Fibrillation

Research Center and Department of Medicine, Montreal Heart Institute and Université de Montréal, and Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.

Manuscript received June 21, 2007; revised manuscript received August 16, 2007, accepted September 7, 2007.

^_* Reprint requests and correspondence: Dr. Stanley Nattel, 5000 Belanger Street East, Montreal H1T 1C8, Quebec, Canada. (Email: stanley.nattel{at}icm-mhi.org).

Atrial fibrillation (AF) is the most common arrhythmia in the clinical setting, and traditional pharmacological approaches have proved to have important weaknesses. Structural remodeling has been observed in both clinical and experimental AF paradigms, and is an important feature of the AF substrate, producing fibrosis that alters atrial tissue composition and function. The precise mechanisms underlying atrial fibrosis are not fully elucidated, but recent experimental studies and clinical investigations have provided valuable insights. A variety of signaling systems, particularly involving angiotensin II and related mediators, seem to be centrally involved in the promotion of fibrosis. This paper reviews the current understanding of how atrial fibrosis creates a substrate for AF, summarizes what is known about the mechanisms underlying fibrosis and its progression, and highlights emerging therapeutic approaches aimed at attenuating structural remodeling to prevent AF.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   AF = atrial fibrillation   AngII = angiotensin II   AT1 = angiotensin II type 1   CHF = congestive heart failure   ECM = extracellular matrix   PDGF = platelet-derived growth factor   TGF = transforming growth factor   VTP = ventricular tachypacing

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