Atrial fibrillation (AF), the most common cardiac arrhythmia, leads to cardiovascular morbidity and mortality. Atrial fibrosis is a major contributor to the therapeutic resistance of the disease. However, the relationship between atrial fibrosis and the progression of AF remains unclear. This research project aims to investigate atrial fibrosis as AF develops and show its reflection in echocardiography. Using a horse model of chronic AF, we will translate the concept of atrial fibrosis to a clinical setting, where diagnostic tools to reliably detect atrial fibrosis are needed for timely and effective prevention and therapy of AF.
Detection of atrial fibrosis by echocardiography, 3D mapping and 3D light sheet imaging – A longitudinal study in an equine atrial fibrillation model
Atrial fibrillation (AF), the most common cardiac arrhythmia, is a major contributor to cardiovascular morbidity and mortality. Treatment is often inadequate, with high recurrence rates of up to 50%. Atrial fibrosis is a major contributor to therapeutic resistance and plays a major role in the progressive nature of AF. Nevertheless, the quantitative relationship between atrial fibrosis and the course of AF is complex, nonlinear and still undetermined. The horse model of AF provides us with a unique opportunity to yield a detailed and up until now unavailable functional and cellular characterization of fibrotic remodeling in AF.
Our research aims to prospectively investigate atrial fibrosis in an equine AF model and show its reflection in echocardiography. This will help us answer the following scientific question: "How does atrial fibrosis impact AF progression and can its severity be identified and quantified by echocardiography and 3D mapping?
This interdisciplinary project will use a well-established horse model to follow changes over a 4-month period in advanced echocardiographic indices (speckle tracking echocardiography) during development of persistent AF in 24 retired racehorses. These findings will be related to morphological alterations (i.e. the extent of myocardial fibrosis) in endomyocardial atrial biopsies detected by use of 3D light sheet imaging technology and other more conventional histopathologic/molecular analyses. Comparison of equine data with that of a large human cohort will enable result interpretation in a human medical context.
Professor Rikke Buhl, University of Copenhagen, Department of Veterinary Clinical Sciences, Section of Large Animal Medicine and Surgery
Professor Colin Schwarzwald, University of Zurich & Clinic Director Equine Hospital
Professor Tor Biering-Sørensen, University of Copenhagen, Department of Biomedical Sciences
Urmas Roostalu, Gubra, principal scientist and project coordinator for cardiovascular diseases