Elsevier

Cardiology Clinics

Volume 15, Issue 1, 1 February 1997, Pages 17-29
Cardiology Clinics

INTRAVASCULAR ULTRASOUND INSIGHTS INTO MECHANISMS OF STENOSIS FORMATION AND RESTENOSIS

https://doi.org/10.1016/S0733-8651(05)70315-5Get rights and content

Intravascular ultrasound (IVUS) allows transmural, tomographic imaging of coronary arteries in humans in vivo, providing unique insights into the pathology of coronary artery disease by defining vessel wall geometry and the major components of the atherosclerotic plaque. Initially, sequential (preintervention and postintervention) IVUS studies were used to study mechanisms of angioplasty devices, including balloon angioplasty, directional coronary atherectomy, high-speed rotational atherectomy, and excimer laser coronary angioplasty.25, 30, 34, 37 More recently, serial (postintervention and follow-up) IVUS studies have been used to study the mechanisms of restenosis; using serial IVUS analysis, the true natural history of disease processes can be studied in humans in vivo. In particular, stenosis formation and restenosis (or late lumen loss) can be subdivided into two distinct underlying components: tissue accumulation and proliferation and arterial remodeling.

Histologic validation of cross-sectional measurements by IVUS have shown that the external elastic membrane cross-sectional area (which represents the area within the border between the hypoechoic media and the echoreflective adventitia) is a reproducible measure of total arterial cross-sectional area.14, 16, 40, 42, 48, 55 Because IVUS cannot measure media thickness accurately,29 plaque plus media cross-sectional area (calculated as external elastic membrane cross-sectional area minus lumen cross-sectional area) is used as a measure of plaque mass. Lastly, the ratio of plaque plus media to external elastic membrane cross-sectional area is a measure of the percent of the arterial cross-sectional area occupied by plaque; this has been called the cross-sectional narrowing, plaque burden, or percent plaque area by different investigators.

Section snippets

GENERAL LIMITATIONS TO ANIMAL MODELS

Diet-induced atherosclerosis in animals and early atherosclerosis in humans is typically lipid-rich; conversely, high-grade chronic coronary artery obstructions in humans usually contain large amounts of both collagen and calcium and relatively little lipid. Collagen and calcium are deposited into and removed from plaques much slower than lipid. No one animal model completely simulates the vascular healing processes following catheter-induced trauma. Most animal models of restenosis occur in

Adaptive Arterial Remodeling in De Novo Lesions

Arterial remodeling is defined as a change in total arterial or external elastic membrane cross-sectional area over time. Arterial remodeling can be bidirectional. Adaptive arterial remodeling (an increase in arterial cross-sectional area) may represent a compensatory response of blood vessels to hemodynamic stress, arterial injury, and cellular proliferation. Adaptive arterial remodeling early in the coronary artery atherosclerotic disease process, as originally described by Glagov and

RESTENOSIS

Restenosis occurs within the first 6 months after 30% to 50% of transcatheter procedures; it remains the major limitation to percutaneous coronary revascularization.6, 18 Catheter-induced vascular injury causes immediate, progressive release of thrombogenic, vasoactive, and mitogenic factors leading to platelet aggregation, thrombus formation, and inflammatory changes, with activation of macrophages and smooth muscle cells. These events induce the production and release of growth factors and

STENTS

Most recently, the authors have studied the mechanism of in-stent restenosis.17 Stents have been shown to reduce restenosis in two randomized clinical trials.8, 52

CONCLUSIONS

IVUS studies indicate that cellular proliferation and plaque accumulation cannot account for the all of the lumen compromise in de novo lesion formation or even for the majority of late lumen loss following nonstent catheter-based interventions. Instead the direction and magnitude of the change in external elastic membrane cross-sectional area (the directional and magnitude of arterial remodeling) appear to be responsible for some of the lumen compromise in de novo lesions and most of late

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    Address reprint requests to Gary S. Mintz, MD, 110 Irving Street NW (4B-1), Washington, DC 20010

    This study was supported in part by the Cardiology Research Foundation and the Medlantic Research Institute, Washington, DC

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    Copyright © 1997 W. B. Saunders Company. Published by Elsevier Inc. All rights reserved.