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      Anti-arrhythmic strategies for atrial fibrillation : The role of computational modeling in discovery, development, and optimization

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          Abstract

          Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with increased risk of cerebrovascular stroke, and with several other pathologies, including heart failure. Current therapies for AF are targeted at reducing risk of stroke (anticoagulation) and tachycardia-induced cardiomyopathy (rate or rhythm control). Rate control, typically achieved by atrioventricular nodal blocking drugs, is often insufficient to alleviate symptoms. Rhythm control approaches include antiarrhythmic drugs, electrical cardioversion, and ablation strategies. Here, we offer several examples of how computational modeling can provide a quantitative framework for integrating multi scale data to: (a) gain insight into multi-scale mechanisms of AF; (b) identify and test pharmacological and electrical therapy and interventions; and (c) support clinical decisions. We review how modeling approaches have evolved and contributed to the research pipeline and preclinical development and discuss future directions and challenges in the field.

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          Author and article information

          Journal
          7905840
          6445
          Pharmacol Ther
          Pharmacol. Ther.
          Pharmacology & therapeutics
          0163-7258
          1879-016X
          21 September 2016
          06 September 2016
          December 2016
          01 December 2017
          : 168
          : 126-142
          Affiliations
          [1 ] Department of Pharmacology, University of California Davis, Davis, USA
          [2 ] Simula Research Laboratory, Oslo, Norway
          Author notes
          [@ ]Correspondence: 451 Health Sciences Drive, GBSF rm 3502, Davis, CA 95616 USA, Phone: (530) 752-4334, Fax: (530) 752-7710, ele.grandi@ 123456gmail.com
          Article
          PMC5140742 PMC5140742 5140742 nihpa817291
          10.1016/j.pharmthera.2016.09.012
          5140742
          27612549
          33299e50-b8f4-47d9-90f7-fa32b4bf18fa
          History
          Categories
          Article

          cardioversion,simulation,systems pharmacology,ablation,atrial selectivity,Antiarrhythmic drugs

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