title: Calcium Handling Abnormalities as a Target for Atrial Fibrillation Therapeutics: How Close to Clinical Implementation?
abstract: Atrial fibrillation (AF) is the most common cardiac arrhythmia with a substantial impact on morbidity and mortality. Antiarrhythmic drugs play a major role in rhythm-control therapy of AF. However, currently available agents exhibit limited efficacy and pronounced adverse effects, notably drug-induced proarrhythmia. Recent experimental studies have identified that Ca handling abnormalities are critical elements in AF pathophysiology with central roles in atrial ectopic activity, reentry, and atrial remodeling suggesting that Ca handling abnormalities could be promising targets for novel AF therapeutics. Here, we summarize key aspects of AF-related Ca-handling abnormalities, describe currently available compounds targeting atrial Ca handling, and highlight potential novel targets and experimental drugs currently under investigation. Finally, we assess how close AF therapeutics based on Ca-handling abnormalities are to clinical implementation.
authors.affiliation: Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany.
authors.forename: Jordi
authors.initials: J
authors.lastname: Heijman
authors.forename: Niels
authors.initials: N
authors.lastname: Voigt
authors.forename: Shokoufeh
authors.initials: S
authors.lastname: Ghezelbash
authors.forename: Ilona
authors.initials: I
authors.lastname: Schirmer
authors.forename: Dobromir
authors.initials: D
authors.lastname: Dobrev
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000008:administration & dosage; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D016503:Drug Delivery Systems / Q000639:trends; D006801:Humans
chemical_list: D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002118:Calcium