Investigating relationships between thromboembolic risk and left atrial structure, function, and flow characteristics as assessed with advanced magnetic resonance techniques

Atrial fibrillation (AF) is associated with alterations in left atrial (LA) blood flow characteristics which, in turn, increase the risk of LA thrombus formation and, consequently, of cardioembolic stroke. Anticoagulation is highly effective in preventing ischaemic stroke in patients with AF and stroke risk factors. More recently, it has been suggested that a cardioembolic aetiology may also underlie a proportion of ischaemic strokes that occur in sinus rhythm (SR) in the context of an atrial myopathic process caused by increased exposure to clinical risk factors, before the onset of AF. To date, it is still unclear whether LA myopathy is linked to increased embolic stroke risk and whether this association is causally determined.
I used advanced cardiovascular magnetic resonance (CMR) methods to investigate the relationship between LA characteristics and ischaemic stroke risk beyond AF, as well as the relative effect of AF and clinical stroke risk factors on LA function and flow characteristics.
First, I developed an application for measuring left atrial (LA) four-dimensional (4D; i.e. on the x, y, z axes over time) involving a MATLAB-based software and post-processing protocols. Reproducibility of LA flow characteristics derived by using this novel application was then assessed in volunteers and in patients with stroke risk factors. LA 4D Flow parameters have an overall good reproducibility and acceptable temporal variability with same-day scan-rescan coefficients of variation (CVs) of 6% for peak velocity, 5% for mean velocity, 7% for vorticity, 9% for vortex volume, and 10% for stasis. From this work, LA peak velocity and vorticity emerged as the parameters with the best technical and inter/intra-observer reproducibility and the least temporal variability.
Next, LA flow characteristics were assessed in 37 patients with persistent AF before and after cardioversion and compared to those of patients in SR with a similar (moderate) stroke risk (N=35) and those obtained in low-risk controls in SR (N=23). Restoration of SR after cardioversion led to improvement in LV systolic function and in all LA 4D flow parameters. In the presence of SR, there were no differences in LA flow characteristics between groups with similar stroke risk, regardless of the history of AF; both, however, were similarly impaired when compared to low-risk controls. From this work, I demonstrated for the first time that patients at moderate stroke risk in SR display altered LA flow characteristics in association with an LA dysfunction and reduced LV diastolic function, regardless of a history of AF.
Finally, in 134 patients with median (Q1-Q3) CHA2DS2VASc of 3 (2-4), LA vorticity was significantly and independently associated with prevalent embolic brain infarcts defined as large non-cortical or cortical brain infarcts. LA vorticity, a measure of the rotational tendency of LA flow, is linked to shear stress, the reduction of which leads to biomechanical platelet activation. By contrast, the presence of embolic brain infarct was not associated with other LA parameters, such as LA volume, function, and flow velocities. After adjusting for age, rhythm during CMR, history of AF, and CHA2DS2VASc, a SD reduction in LA vorticity remained associated with a 2-fold higher risk of embolic brain infarcts. These results remained statistically significant in the subgroup of patients in SR without a diagnosis of AF (N=66, P<0.05) and after adjusting for LV/LA structural and functional parameters. Notably, neither LA vorticity nor any other LA flow parameter was associated with lacunar (non-embolic) brain infarcts.
Taken together, these findings indicate that LA flow parameters have a potential for refining stroke risk stratification, and thus the selection of patients who would benefit from anticoagulation. Further studies in large prospective cohorts are now needed to assess whether LA 4D flow parameters predict incident cardioembolic events, and whether prescription of anti-thrombotic therapy based on a risk scores including these parameters would lead to a cost-effective improvement in patient management.

Advisor: Casadei, B
Wijesurendra, R
Ferreira, V