title: Feasibility of selection of antiarrhythmic drug treatment on the basis of arrhythmogenic mechanism - Relevance of electrical restitution, wavebreak and rotors.
abstract: Antiarrhythmic drug therapy has seen significant challenges over the past 3 decades with unexpected results from clinical trials such as CAST, SWORD and more recently PALLAS showing harm in patients whom antiarrhythmic drugs were given based on their intended antiarrhythmic actions and previously demonstrated efficacy. These results question whether the precise mechanism of action of the drugs was understood and highlight the complexity of the situation where there is the combination of multiple actions of the antiarrhythmic drugs on various molecular systems, some of which may be unknown with associated adverse outcome, and their interaction with pre-existing abnormality in disease states in patients treated. In addition, there is no effective drug strategy for complex arrhythmias such as atrial and ventricular fibrillation. Their complex dynamics are not adequately described by the classical mechanisms of automaticity, triggered activity and re-entry. Experimental data showing that flattening of the electrical restitution curve can convert ventricular fibrillation into stable tachycardia and prevent its initiation via wavebreak, and the advancement of computation biology in the describing the behaviour of wavetip and rotors in driving fibrillation have ignited the quest for more detailed understanding of the mechanisms underlying these complex arrhythmias. Their precise ionic basis which could be targeted for drug therapy remains to be fully characterised and tested in appropriate disease models and preparations. This review summarises some of these developments in the context of antiarrhythmic drug therapy consideration.
authors.affiliation: Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, LE3 9QP, UK; National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, UK; University Hospitals of Leicester NHS Trust, Glenfield Hospital, Leicester, UK. Electronic address: gan1@le.ac.uk.
authors.forename: G André
authors.initials: GA
authors.lastname: Ng
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000145:classification / Q000494:pharmacology / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans
chemical_list: D000889:Anti-Arrhythmia Agents
keywords: Anti-arrhythmic drug; Fibrillation; Restitution; Rotor