Atrial fibrillation (AF) is the most common age-related cardiac arrhythmia. It is a progressive disease, which hampers successful treatment. 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.

Atrial Fibrillation, Diagnosis, Heat Shock Protein, Therapy
hdl.handle.net/1765/88067
Journal of Atrial Fibrillation
Erasmus MC: University Medical Center Rotterdam

van Marion, D.M.S, Lanters, E.A.H, Wiersma, M, Allessie, M.A, Brundel, B.J.J.M, & de Groot, N.M.S. (2015). Diagnosis and therapy of atrial fibrillation: The past, the present and the future. Journal of Atrial Fibrillation (Vol. 8, pp. 51–60). Retrieved from http://hdl.handle.net/1765/88067