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Atrial fibrillation: effects beyond the atrium?

ABSTRACT: Atrial fibrillation (AF) is the most common sustained clinical arrhythmia and is associated with significant morbidity, mostly secondary to heart failure and stroke, and an estimated two-fold increase in premature death. Efforts to increase our understanding of AF and its complications have focused on unravelling the mechanisms of electrical and structural remodelling of the atrial myocardium. Yet, it is increasingly recognized that AF is more than an atrial disease, being associated with systemic inflammation, endothelial dysfunction, and adverse effects on the structure and function of the left ventricular myocardium that may be prognostically important. Here, we review the molecular and in vivo evidence that underpins current knowledge regarding the effects of human or experimental AF on the ventricular myocardium. Potential mechanisms are explored including diffuse ventricular fibrosis, focal myocardial scarring, and impaired myocardial perfusion and perfusion reserve. The complex relationship between AF, systemic inflammation, as well as endothelial/microvascular dysfunction and the effects of AF on ventricular calcium handling and oxidative stress are also addressed. Finally, consideration is given to the clinical implications of these observations and concepts, with particular reference to rate vs. rhythm control.

SUBMITTER: Wijesurendra RS

PROVIDER: S-EPMC4339707 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Atrial fibrillation: effects beyond the atrium?

Wijesurendra Rohan S RS Casadei Barbara B

Cardiovascular research 20150112 3

Atrial fibrillation (AF) is the most common sustained clinical arrhythmia and is associated with significant morbidity, mostly secondary to heart failure and stroke, and an estimated two-fold increase in premature death. Efforts to increase our understanding of AF and its complications have focused on unravelling the mechanisms of electrical and structural remodelling of the atrial myocardium. Yet, it is increasingly recognized that AF is more than an atrial disease, being associated with system ...[more]

PMID: 25587048

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Project description:Pulmonary vein isolation (PVI) with radiofrequency ablation (RFA) is the cornerstone of atrial fibrillation (AF) therapy, but few strategies exist for when it fails. To guide RFA, phase singularity (PS) mapping locates reentrant electrical waves (rotors) that perpetuate AF. The goal of this study was to test existing and develop new RFA strategies for terminating rotors identified with PS mapping. It is unsafe to test experimental RFA strategies in patients, so they were evaluated in silico using a bilayer computer model of the human atria with persistent AF (pAF) electrical (ionic) and structural (fibrosis) remodeling. pAF was initiated by rapidly pacing the right (RSPV) and left (LSPV) superior pulmonary veins during sinus rhythm, and rotor dynamics quantified by PS analysis. Three RFA strategies were studied: (i) PVI, roof, and mitral lines; (ii) circles, perforated circles, lines, and crosses 0.5-1.5 cm in diameter/length administered near rotor locations/pathways identified by PS mapping; and (iii) 4-8 lines streamlining the sequence of electrical activation during sinus rhythm. As in pAF patients, 2 ± 1 rotors with cycle length 185 ± 4 ms and short PS duration 452 ± 401 ms perpetuated simulated pAF. Spatially, PS density had weak to moderate positive correlations with fibrosis density (RSPV: r = 0.38, p = 0.35, LSPV: r = 0.77, p = 0.02). RFA PVI, mitral, and roof lines failed to terminate pAF, but RFA perforated circles and lines 1.5 cm in diameter/length terminated meandering rotors from RSPV pacing when placed at locations with high PS density. Similarly, RFA circles, perforated circles, and crosses 1.5 cm in diameter/length terminated stationary rotors from LSPV pacing. The most effective strategy for terminating pAF was to streamline the sequence of activation during sinus rhythm with >4 RFA lines. These results demonstrate that co-localizing 1.5 cm RFA lesions with locations of high PS density is a promising strategy for terminating pAF rotors. For patients immune to PVI, roof, mitral, and PS guided RFA strategies, streamlining patient-specific activation sequences during sinus rhythm is a robust but challenging alternative.

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Atrial fibrillation: effects beyond the atrium?

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Atrial fibrillation: effects beyond the atrium?

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