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.

Background-Aortic valve stenosis (AS) can cause angina despite unobstructed coronary arteries, which may be related to increased compression of the intramural microcirculation, especially at the subendocardium. We assessed coronary wave intensity and phasic flow velocity patterns to unravel changes in cardiac-coronary interaction because of transcatheter aortic valve implantation (TAVI). Methods and Results-Intracoronary pressure and flow velocity were measured at rest and maximal hyperemia in undiseased vessels in 15 patients with AS before and after TAVI and in 12 control patients. Coronary flow reserve, systolic and diastolic velocity time integrals, and the energies of forward (aorta-originating) and backward (microcirculatoryoriginating) coronary waves were determined. Coronary flow reserve was 2.8±0.2 (mean±SEM) in control and 1.8±0.1 in AS (P<0.005) and was not restored by TAVI. Compared with control, the resting backward expansion wave was 45% higher in AS. The peak of the systolic forward compression wave was delayed in AS, consistent with a delayed peak aortic pressure, which was partially restored after TAVI. The energy of forward waves doubled after TAVI, whereas the backward expansion wave increased by >30%. The increase in forward compression wave with TAVI was related to an increase in systolic velocity time integral. AS or TAVI did not alter diastolic velocity time integral. Conclusions-Reduced coronary forward wave energy and systolic velocity time integral imply a compromised systolic flow velocity with AS that is restored after TAVI, suggesting an acute relief of excess compression in systole that likely benefits subendocardial perfusion. Vasodilation is observed to be a major determinant of backward waves. (Circ Cardiovasc Interv. 2016;9:e002356.

Baseline assessment of functional stenosis severity has been proposed as a practical alternative to hyperemic indices. However, intact autoregulation mechanisms may affect intracoronary hemodynamics. The aim of this study was to investigate the effect of changes in aortic pressure (Pa) and heart rate (HR) on baseline coronary hemodynamics and functional stenosis assessment. In 15 patients (55 ± 3% diameter stenosis) Pa, intracoronary pressure (Pd) and flow velocity were obtained at control, and during atrial pacing at 120 bpm, increased Pa (+30 mmHg) with intravenous phenylephrine (PE), and elevated Pa while pacing at sinus heart rate (PE + sHR). We derived rate pressure product (RPP = systolic Pa × HR), baseline microvascular resistance (BMR = Pd/velocity), and stenosis resistance [BSR = (Pa − Pd)/velocity] as well as whole-cycle Pd/Pa. Tachycardia (120 ± 1 bpm) raised RPP by 74% vs. control. Accordingly, BMR decreased by 27% (p < 0.01) and velocity increased by 36% (p < 0.05), while Pd/Pa decreased by 0.05 ± 0.02 (p < 0.05) and BSR remained similar to control. Raising Pa to 121 ± 3 mmHg (PE) with concomitant reflex bradycardia increased BMR by 26% (p < 0.001) at essentially unchanged RPP and velocity. Consequently, BSR and Pd/Pa were only marginally affected. During PE + sHR, velocity increased by 21% (p < 0.01) attributable to a 46% higher RPP (p < 0.001). However, BMR, BSR, and Pd/Pa remained statistically unaffected. Nonetheless, the interventions tended to increase functional stenosis severity, causing Pd/Pa and BSR of borderline lesions to cross the diagnostic threshold. In conclusion, coronary microvascular adaptation to physiological conditions affecting metabolic demand at rest influences intracoronary hemodynamics, which may lead to altered basal stenosis indices used for clinical decision-making.