Focal In-Stent Restenosis Near Step-Up
Roles of Low and Oscillating Shear Stress?
A 64-year-old man with exercise-induced chest pain underwent coronary angioplasty of his stenosed left anterior descending coronary artery (segments 6 and 7). We recanalized the artery and placed a 3.0×18-mm stent distally and a 3.0×28-mm stent proximally. The residual diameter stenosis at the proximal edge was 26% on quantitative coronary angiography (QCA). Intravascular ultrasound (IVUS) showed an in-stent lumen area of 7.5 mm2, which exceeded that immediate proximal of the stent (5.6±0.8 mm2) and caused a so-called “step-up” phenomenon (Figure 1A and 1B, open arrow). Although the stent was well apposed and deployed as indicated by IVUS, the patient presented with worsening anginal symptoms 4 months later; both the angiogram and IVUS showed focal in-stent restenosis at the proximal edge of the proximal stent (78% on QCA) and mild diffuse neointimal hyperplasia (NIH) through the entire length of the stent.
The mechanism of in-stent restenosis has not been fully elucidated, despite numerous animal and human investigations. Stent placement may cause changes in 3D geometry, coronary flow velocity profile, and, as a consequence, in shear stress (SS). It is known that low oscillating SS gives rise to the expression of several growth factors. No clinical evidence has been provided for the potential importance of oscillating SS and its localizing role in in-stent restenosis. Because this patient had been included in a prospective 6-month follow-up study to investigate the association between (oscillating) SS and NIH, angiography and IVUS (ANGUS) had been performed to 3-dimensionally reconstruct the lumen of the stented coronary artery (Figure 1B). Doppler flow (Figure 2B) and blood viscosity measurements were used as input conditions for application of computational fluid dynamics in this 3D reconstruction. The result of these calculations was the SS at the wall as a function of time over the cardiac cycle. The ANGUS procedure was repeated when the patient presented at 4 months, and NIH was determined from this 3D reconstruction (Figure 1F). As found previously, NIH was highest near the locations where average SS was low (Figure 1E, 1F, and 1G). Subsequently, the temporal SS pattern in the region of the step-up (Figure 1C) was evaluated. This analysis showed that the SS vectors were either permanently or temporarily retrogradely directed near the “corner” of the step-up. This indicates the existence of a region of flow separation (Figure 1D). In Figure 2C, locations showing retrograde axial velocities are presented in black at 5 time points as indicated in the Doppler recordings (Figure 2B). At locations that temporarily experience retrograde velocities, SS alters direction periodically. Interestingly, those locations of oscillating SS were nearest to the area of highest NIH (Figure 2A). Our findings warrant further studies to clarify the benefits of the step-up phenomenon.
The editor of Images in Cardiovascular Medicine is Hugh A. McAllister, Jr, MD, Chief, Department of Pathology, St Luke’s Episcopal Hospital and Texas Heart Institute, and Clinical Professor of Pathology, University of Texas Medical School and Baylor College of Medicine.
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