Emerging Antiarrhythmic Drugs for Atrial Fibrillation

Arnela Saljic, Jordi Heijman, Dobromir Dobrev*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftReviewForskningpeer review

24 Citationer (Scopus)
15 Downloads (Pure)

Abstract

Atrial fibrillation (AF), the most common cardiac arrhythmia worldwide, is driven by complex mechanisms that differ between subgroups of patients. This complexity is apparent from the different forms in which AF presents itself (post-operative, paroxysmal and persistent), each with heterogeneous patterns and variable progression. Our current understanding of the mechanisms responsible for initiation, maintenance and progression of the different forms of AF has increased significantly in recent years. Nevertheless, antiarrhythmic drugs for the management of AF have not been developed based on the underlying arrhythmia mechanisms and none of the currently used drugs were specifically developed to target AF. With the increased knowledge on the mechanisms underlying different forms of AF, new opportunities for developing more effective and safer AF therapies are emerging. In this review, we provide an overview of potential novel antiarrhythmic approaches based on the underlying mechanisms of AF, focusing both on the development of novel antiarrhythmic agents and on the possibility of repurposing already marketed drugs. In addition, we discuss the opportunity of targeting some of the key players involved in the underlying AF mechanisms, such as ryanodine receptor type-2 (RyR2) channels and atrial-selective K+-currents (IK2P and ISK) for antiarrhythmic therapy. In addition, we highlight the opportunities for targeting components of inflammatory signaling (e.g., the NLRP3-inflammasome) and upstream mechanisms targeting fibroblast function to prevent structural remodeling and progression of AF. Finally, we critically appraise emerging antiarrhythmic drug principles and future directions for antiarrhythmic drug development, as well as their potential for improving AF management.

OriginalsprogEngelsk
Artikelnummer4096
TidsskriftInternational Journal of Molecular Sciences
Vol/bind23
Udgave nummer8
Sider (fra-til)1-32
ISSN1661-6596
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
Funding: This work for supported by funding from the Independent Research Fund Denmark (102900011B to A.S.), the Netherlands Organization for Scientific Research (NWO/ZonMW Vidi 09150171910029 to J.H.), the National Institutes of Health (R01HL136389, R01HL131517 and R01HL089598 to D.D.), the German Research Foundation (DFG, Do 769/4-1 to D.D.), and the European Union (large-scale integrative project MEASTRIA, No. 965286 to D.D.).

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

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