title: Diagnosis and Therapy of Atrial Fibrillation: The Past, The Present and The Future.
abstract: Atrial fibrillation (AF) is the most common age-related cardiac arrhythmia. It is a progressive disease, which makes treatment difficult. The progression of AF is caused by the accumulation of damage in cardiomyocytes which makes the atria more vulnerable for AF. Especially structural remodeling and electrical remodeling, together called electropathology are sustainable in the atria and impair functional recovery to sinus rhythm after cardioversion. The exact electropathological mechanisms underlying persistence of AF are at present unknown. High resolution wavemapping studies in patients with different types of AF showed that longitudinal dissociation in conduction and epicardial breakthrough were the key elements of the substrate of longstanding persistent AF. A double layer of electrically dissociated waves propagating transmurally can explain persistence of AF (Double Layer Hypothesis) but the molecular mechanism is unknown. Derailment of proteasis -defined as the homeostasis in protein synthesis, folding, assembly, trafficking, guided by chaperones, and clearance by protein degradation systems - may play an important role in remodeling of the cardiomyocyte. As current therapies are not effective in attenuating AF progression, step-by-step analysis of this process, in order to identify potential targets for drug therapy, is essential. In addition, novel mapping approaches enabling assessment of the degree of electropathology in the individual patient are mandatory to develop patient-tailored therapies. The aims of this review are to 1) summarize current knowledge of the electrical and molecular mechanisms underlying AF 2) discuss the shortcomings of present diagnostic instruments and therapeutic options and 3) to present potential novel diagnostic tools and therapeutic targets.
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University Institute for Drug Exploration (GUIDE), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Denise M S
authors.initials: DM
authors.lastname: van Marion
authors.affiliation: Department of Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Eva A H
authors.initials: EA
authors.lastname: Lanters
authors.affiliation: Department of Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Marit
authors.initials: M
authors.lastname: Wiersma
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University Institute for Drug Exploration (GUIDE), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Maurits A
authors.initials: MA
authors.lastname: Allessie
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University Institute for Drug Exploration (GUIDE), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; Department of Clinical Pharmacy and Pharmacology, University Institute for Drug Exploration (GUIDE), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Bianca B J J M
authors.initials: BB
authors.lastname: Brundel
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University Institute for Drug Exploration (GUIDE), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Natasja M S
authors.initials: NM
authors.lastname: de Groot
keywords: Atrial Fibrillation; Diagnosis; Heat Shock Protein; Therapy