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Atrial fibrillation ablation: A death-defying endeavour? Jason G. Andrade MD, Marc W. Deyell MD, Laurent Macle MD

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S1547-5271(14)00550-5 http://dx.doi.org/10.1016/j.hrthm.2014.05.019 HRTHM5782

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Heart Rhythm

Cite this article as: Jason G. Andrade MD, Marc W. Deyell MD, Laurent Macle MD, Atrial fibrillation ablation: A death-defying endeavour?, Heart Rhythm, http://dx.doi.org/ 10.1016/j.hrthm.2014.05.019 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Atrial fibrillation ablation: A death-defying endeavour? Jason G. Andrade MD1,2; Marc W. Deyell MD2; Laurent Macle MD1 From 1the Electrophysiology Service at the Montreal Heart Institute and the Department of Medicine, Université de Montréal, Montreal, Canada; and 2The Department of Medicine, The University of British Columbia, British Columbia, Canada

Short Title: Please address all correspondence to: Dr. Jason Andrade Electrophysiology Service Vancouver General Hospital Ph: Fax: E-mail: [email protected] Word Count: Journal Subject Codes: [5] Arrhythmias, clinical electrophysiology, drugs [22] Ablation/ICD/surgery [106] Electrophysiology

Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice.1 In addition to reductions in both functional status and quality of life, AF is associated with a significant risk of stroke, a risk that is increased 5-fold compared to the general population.2 Moreover, patients with AF are at a potentially increased risk of mortality due to a combination of altered hemodynamics, AV dysynchrony, progressive atrial and ventricular mechanical dysfunction. Independent of other known risk factors, the presence of AF is associated with a doubling in the risk of death when compared to non-AF controls.3-5 This has been noted in the general population, in the heart failure population, as well as in patients with stable coronary artery disease.3-5 Unfortunately, despite advances in treatment strategies AFrelated mortality has remained relatively static. To date only anticoagulation has been shown to improve survival.6 However, if AF is associated with an increased mortality then restoration of sinus rhythm must be beneficial? In the past decade, several large randomized, controlled trials have compared the relative risks and benefits of ventricular rate control vs. strategies of pharmacologic restoration and maintenance of sinus rhythm. Collectively these large prospective randomized trials have demonstrated a strategy of rate control to be at least equivalent to a strategy of sinus rhythm restoration in terms of all-cause mortality (OR=0.87; 95%CI 0.74-1.02; p=0.09) and risk of stroke (OR=0.5; 95%CI 0.14-1.83; p=0.30).7 Yet our tools to maintain sinus rhythm are imperfect and so the question regarding possible mortality benefit for patients successfully maintained on efficacious sinus rhythm restoration therapy has persisted, largely driven by post-hoc analyses of the AFFIRM, DIAMOND, CHFSTAT, and ATHENA trials.8-11 In the former a time-dependent “on-treatment” analyses demonstrated that the presence of sinus rhythm was associated with a lower risk of death (HR 0.53; 95%CI 0.42-0.70; p

Atrial fibrillation ablation: a death-defying endeavor?

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