Left atrial wall shear stress distribution correlates with atrial endocardial electrogram voltage and fibrosis in patients with atrial fibrillation

Left atrial (LA) wall fibrosis plays an important role in the perpetuation of atrial fibrillation (AF) since the abnormal electrophysiological properties of the fibrotic areas sustains the arrhythmia by favoring both re-entry circuits as well as abnormal impulse generation. Despite its crucial contribution, the mechanisms by which LA fibrosis develops are not well understood.

The LA wall is constantly exposed to the hydraulic forces exerted by the blood flow arriving from the pulmonary veins. The purpose of the present study was to examine the association between regional wall shear stress and areas with fibrosis in the LA of patients with AF.

15 patients (13 males, mean age 61±11 years) with AF, no significant mitral regurgitation and clinical indication for a primary catheter ablation were prospectively recruited for the study. All participants underwent a baseline three-dimensional electro-anatomical mapping of the LA during the ablation procedure and a pre-interventional cardiovascular magnetic resonance (CMR) imaging with phase contrast for mitral flow estimation and Gadolinium injection for LA fibrosis detection. Fibrotic areas were detected either by low bipolar voltage (BV≤0.5mV) and/or by areas with enhanced late Gadolinium uptake as assessed by the image intensity ratio (IIR≥1.2). For all subjects, a detailed 3D anatomical model of the LA was extracted from the invasive electro-anatomical maps and was used to calculate regional time-averaged wall shear stress (TAWSS) and blood age (BA), an index of blood stagnation, by performing patient-specific computational fluid dynamic simulations.

Globally, areas around the pulmonary veins and the LA roof exhibited the highest values of TAWSS. In all cases, high TAWSS was strongly correlated with low voltage (n=15, r from -0.002 to -0.449, p<0.01) and enhanced late Gadolinium uptake (n=12, r from 0.071 to 0.475, p<0.001). Fibrotic areas as detected by both low BV and high IIR were more prevalent in areas exposed to high TAWSS (21.6% vs 8.1% and 26.2% vs 13.2% respectively, p<0.001). Inversely, in all but one case, areas with low TAWSS presented more intense blood stagnation as assessed by the highest BA (r from -0.268 to - 0.688, p<0.001).

In patients with AF, regional high TAWSS is associated with corresponding CMR biomarkers of left atrial wall fibrosis and electrical scaring. Inversely, areas with low TAWSS are associated with blood stagnation and could favor thrombus formation. This may provide insights of a novel pathophysiological mechanism explaining the characteristic atrial electrical remodeling and thrombus formation seen in patients with AF.