Early Atherosclerotic Changes in Coronary Arteries are Associated with Endothelium Shear Stress Contraction/Expansion Variability

Abstract

Although unphysiological wall shear stress (WSS) has become the consensus hemodynamic mechanism for coronary atherosclerosis, the complex biomechanical stimulus affecting atherosclerosis evolution is still undetermined. This has motivated the interest on the contraction/expansion action exerted by WSS on the endothelium, obtained through the WSS topological skeleton analysis. This study tests the ability of this WSS feature, alone or combined with WSS magnitude, to predict coronary wall thickness (WT) longitudinal changes. Nine coronary arteries of hypercholesterolemic minipigs underwent imaging with local WT measurement at three time points: baseline (T1), after 5.6 ± 0.9 (T2), and 7.6 ± 2.5 (T3) months. Individualized computational hemodynamic simulations were performed at T1 and T2. The variability of the WSS contraction/expansion action along the cardiac cycle was quantified using the WSS topological shear variation index (TSVI). Alone or combined, high TSVI and low WSS significantly co-localized with high WT at the same time points and were significant predictors of thickening at later time points. TSVI and WSS magnitude values in a physiological range appeared to play an atheroprotective role. Both the variability of the WSS contraction/expansion action and WSS magnitude, accounting for different hemodynamic effects on the endothelium, (1) are linked to WT changes and (2) concur to identify WSS features leading to coronary atherosclerosis.

Risk of myocardial infarction based on endothelial shear stress analysis using coronary angiography

“…3, Supplemental Figs. [10][11][12]. The single strongest predictor of MI at the lesion level was TSVI (adjusted HR 6.21, 95%CI 3.13-12.3, p < 0.001; Supplemental Table 8).…”

“…The quantitative characterization of endothelial shear forces included the following WSS-based descriptors (Supplemental Table 1): time-averaged wall shear stress (TAWSS), obtained by averaging the local values of WSS magnitude along the cardiac cycle (Supplemental Fig. 1) [12]; oscillatory shear index (OSI) [13]; transverse WSS (transWSS) [14]; TAWSS axial component (TAWSS ax ) and secondary component (TAWSS sc ) [15]; relative residence time (RRT) [16]; and topological shear variation index (TSVI) [8][9][10]. The next paragraph further expands on TSVI.…”

“…Among WSS topological skeleton features, TSVI was initially associated with development of long-term re-stenosis after carotid endarterectomy in humans [8]. Recently, TSVI has been linked with early atherosclerotic changes in coronary arteries in preclinical swine models [10]. Of note, high TSVI not only co-localized with higher wall thickness, but also predicted wall thickening longitudinally [10].…”

“…In addition, WSS has been associated with vulnerable transformation of atherosclerotic lesions: low WSS has been linked to atherosclerosis progression, whereas high WSS has been associated with platelet activation and plaque rupture [6,7]. More recently, WSS-based descriptors able to characterize the contraction/expansion action of endothelial shear forces along the cardiac cycle were associated with vascular pathophysiological processes in coronary and extra-coronary territories [8][9][10]. In particular, a recent longitudinal study on swine models showed that early atherosclerotic changes in coronary arteries are associated with the endothelium shear stress contraction/expansion variability along the cardiac cycle, captured by the WSS-based quantity topological shear variation index (TSVI) [10].…”

Comparison of Swine and Human Computational Hemodynamics Models for the Study of Coronary Atherosclerosis

“…For this reason, several large animal models based on the use of rabbits, pigs, or non-human primates, have been adopted to e.g. : 1) study coronary atherosclerosis natural history (Getz and Reardon, 2012;Daugherty et al, 2017); 2) evaluate the efficacy of clinical treatment procedures (Shin et al, 2021); 3) identify predictive tools for the evolution of the disease, which most of the time is asymptomatic (De Nisco et al, 2020;Hoogendoorn et al, 2020;Mazzi et al, 2021). Most of the animal model-based studies on atherosclerosis onset and progression imply that their findings reliably inform human studies, sometimes suggesting a direct translation to humans.…”