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Circ Res. 2018 Mar 2;122(5):752-773. doi: 10.1161/CIRCRESAHA.117.311081.

Translational Challenges in Atrial Fibrillation.

Author information

1
From the Department of Cardiology, Cardiovascular Research Institute Maastricht, Faculty of Health, Medicine, and Life Sciences, Maastricht University, The Netherlands (J.H.); Department of Medicine, Montreal Heart Institute and Université de Montréal, Canada (J.-B.G., S.N.); University Hospital of Saint-Étienne, University Jean Monnet, Saint-Étienne, France (J.-B.G.); Institute of Pharmacology, West German Heart and Vascular Center, Faculty of Medicine, University Duisburg-Essen (D.D., S.N.); and Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada (S.N.).
2
From the Department of Cardiology, Cardiovascular Research Institute Maastricht, Faculty of Health, Medicine, and Life Sciences, Maastricht University, The Netherlands (J.H.); Department of Medicine, Montreal Heart Institute and Université de Montréal, Canada (J.-B.G., S.N.); University Hospital of Saint-Étienne, University Jean Monnet, Saint-Étienne, France (J.-B.G.); Institute of Pharmacology, West German Heart and Vascular Center, Faculty of Medicine, University Duisburg-Essen (D.D., S.N.); and Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada (S.N.). stanley.nattel@icm-mhi.org.

Abstract

Atrial fibrillation (AF) is the most common sustained heart rhythm disorder and is associated with substantial morbidity and mortality. Current treatment options for AF have significant limitations. Basic research has provided information on mechanisms relevant to the management of AF and promises to contribute significantly to future advances, yet many important translational challenges remain. Here, we analyze the therapeutic limitations for which improvement is needed, consider the translational opportunities presented by recent scientific and technological developments, and attempt to look into the future of where these may lead. We first review the limitations of current AF management, with a focus on rhythm control therapy. These include arrhythmia complications, progression to advanced treatment-resistant forms, insufficient effectiveness of available therapeutic options, adverse consequences of therapy, and difficulties in new therapeutic development. The translational challenges in addressing these shortcomings are then addressed, including (1) defining actionable patient-specific arrhythmia mechanisms to enable personalized therapy; (2) identifying and treating key dynamic modulators controlling AF initiation and progression; (3) achieving atrial-restricted targeting of specific molecular arrhythmia mechanisms; and (4) clarifying the response of the substrate to interventions. For each of these, we describe the translational goal and the opportunities created by recent advances in cardiac imaging, computational modeling, rhythm monitoring, ablation technology, and preclinical studies in human samples and animal models. Finally, we consider the prospects for future solutions that might appreciably improve our ability to understand and manage the arrhythmia over the years to come.

KEYWORDS:

anti-arrhythmia agents; atrial fibrillation; catheter ablation; precision medicine; translational medical research

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