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Aims: Atherosclerotic plaque development has been associated with wall shear stress (WSS). However, the multidirectionality of blood flow, and thus of WSS, is rarely taken into account. The purpose of this study was to comprehensively compare five metrics that describe (multidirectional) WSS behaviour and assess how WSS multidirectionality affects coronary plaque initiation and progression., Methods and Results: Adult familial hypercholesterolaemic pigs (n = 10) that were fed a high-fat diet, underwent imaging of the three main coronary arteries at three-time points [3 (T1), 9 (T2), and 10-12 (T3) months]. Three-dimensional geometry of the arterial lumen, in combination with local flow velocity measurements, was used to calculate WSS at T1 and T2. For analysis, arteries were divided into 3 mm/45° sectors (n = 3648). Changes in wall thickness and final plaque composition were assessed with near-infrared spectroscopy-intravascular ultrasound, optical coherence tomography imaging, and histology. Both in pigs with advanced and mild disease, the highest plaque progression rate was exclusively found at low time-averaged WSS (TAWSS) or high multidirectional WSS regions at both T1 and T2. However, the eventually largest plaque growth was located in regions with initial low TAWSS or high multidirectional WSS that, over time, became exposed to high TAWSS or low multidirectional WSS at T2. Besides plaque size, also the presence of vulnerable plaque components at the last time point was related to low and multidirectional WSS. Almost all WSS metrics had good predictive values for the development of plaque (47-50%) and advanced fibrous cap atheroma (FCA) development (59-61%)., Conclusion: This study demonstrates that low and multidirectional WSS promote both initiation and progression of coronary atherosclerotic plaques. The high-predictive values of the multidirectional WSS metrics for FCA development indicate their potential as an additional clinical marker for the vulnerable disease., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

OBJECTIVE. Coronary CT angiography (CCTA)-based methods allow noninvasive estimation of fractional flow reserve (cFFR), recently through use of a machine learning (ML) algorithm (cFFR ML ). However, attenuation values vary according to the tube voltage used, and it has not been shown whether this significantly affects the diagnostic performance of cFFR and cFFR ML . Therefore, the purpose of this study is to retrospectively evaluate the effect of tube voltage on the diagnostic performance of cFFR ML . MATERIALS AND METHODS. A total of 525 coronary vessels in 351 patients identified in the MACHINE consortium registry were evaluated in terms of invasively measured FFR and cFFR ML . CCTA examinations were performed with a tube voltage of 80, 100, or 120 kVp. For each tube voltage value, correlation (assessed by Spearman rank correlation coefficient), agreement (evaluated by intraclass correlation coefficient and Bland-Altman plot analysis), and diagnostic performance (based on ROC AUC value, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy) of the cFFR ML in terms of detection of significant stenosis were calculated. RESULTS. For tube voltages of 80, 100, and 120 kVp, the Spearman correlation coefficient for cFFR ML in relation to the invasively measured FFR value was ρ = 0.684, ρ = 0.622, and ρ = 0.669, respectively ( p < 0.001 for all). The corresponding intraclass correlation coefficient was 0.78, 0.76, and 0.77, respectively ( p < 0.001 for all). Sensitivity was 100.0%, 73.5%, and 85.0%, and specificity was 76.2%, 79.0%, and 72.8% for tube voltages of 80, 100, and 120 kVp, respectively. The ROC AUC value was 0.90, 0.82, and 0.80 for 80, 100, and 120 kVp, respectively ( p < 0.001 for all). CONCLUSION. CCTA-derived cFFR ML is a robust method, and its performance does not vary significantly between examinations performed using tube voltages of 100 kVp and 120 kVp. However, because of rapid advancements in CT and postprocessing technology, further research is needed.