Non-clinical cardiology Laboratory

A major research focus of the Cardiovascular Research group is Atrial fibrillation (AF). AF is the most common sustained cardiac rhythm disturbance to affect humans. It is strongly associated with adverse cardiovascular outcomes, predominantly related to ischaemic stroke. Its frequency rises rapidly after the sixth decade with a prevalence of approximately of 10% in subjects over 75 years of age. The major morbidity and mortality that is derived from atrial fibrillation comes from ischaemic cerebrovascular events. The rate of strokes in patients not on anti-thrombotic therapy is increased almost 5-fold in the absence of structural heart disease and may be as high as 17.5 fold in some substrates. In addition, evidence suggests that patients with AF frequently also have silent strokes. While this stroke risk is significantly reduced by oral anticoagulation this anti-thrombotic therapy (warfarin) is not without its own risks, particularly in the elderly. Our research in this area is at the interaction between basic and clinical science. We aim  to identify novel therapeutic targets for the treatment of cardiac rhythm disturbances.

Ischaemic strokes are thought to be largely embolic in nature, derived from thrombus in the left atrium and usually from the left atrial appendage. This is based on operative and more recent trans-oesophageal echocardiographic evidence. The main pathogenesis behind thrombus formation in the left atrium has to date been felt to relate predominantly to blood stasis and atrial mechanical dysfunction. However, the exact mechanisms by which mechanical dysfunction lead to thrombosis remains unknown. While alternative postulates have been presented to account for the heightened risk of thrombosis, a paucity of evidence exists. Endothelial and platelet dysfunction have been strongly associated with vascular disease and associated risk factors, however little is known to date on the impact these have in atrial fibrillation and associated thromboembolic complications.

It is hypothesized that altered endothelial and platelet function are the mediators for the formation of atrial thrombus. In particular, that atrial disease states, in the absence of atrial arrhythmias, may also be associated with the heightened risk of stroke by alteration of endothelial and platelet function.