Intravascular Ultrasound to Discern Device-Specific Effects and Mechanisms of Restenosis*

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Abstract

Restenosis continues to be the “Achilles' heel” of transcatheter interventions. While attempts to reduce restenosis by inhibiting cellular proliferation through pharmacologic or mechanical means have been unsuccessful, stents, which inhibit acute recoil and chronic remodeling, have been shown convincingly to reduce restenosis in 2 randomized clinical trials. Intravascular ultrasound (IVUS) allows transmural, tomographic imaging of coronary arteries in humans in vivo to subdivide restenosis into the two basic underlying components: tissue proliferation and arterial remodeling. In studies performed at the Washington Hospital Center, in nonstented lesions 73% of late lumen loss was due to arterial remodeling (a decrease in arterial, or external elastic membrane cross-sectional area) and 27% was due to tissue growth (an increase in plaque plus media cross-sectional area). These findings were confirmed by 2 other studies: the Optimal Atherectomy Restenosis Study (OARS) and the Serial Ultrasound analysis of REstenosis (SURE) Trial. IVUS was also used to study the mechanisms by which stents reduce restenosis. Stents created a larger final lumen cross-sectional area and, for all practical purposes, abolished arterial remodeling to offset a stent-related increase in neointimal tissue accumulation. Neointimal hyperplasia is solely responsible for in-stent restenosis and therefore appears to be a pure model for studying strategies to limit tissue proliferation. (Am J Cardiol 1996;78(suppl 3A):18–22)

Section snippets

IVUS STUDIES OF ARTERIAL REMODELING AND RESTENOSIS IN NONSTENTED LESIONS

We have performed serial IVUS studies in 336 lesions in 306 patients; 212 native coronary target lesions in 209 patients involved nonstent interventional procedures including balloon angioplasty (n = 29), directional coronary atherectomy (n = 114), high-speed rotational atherectomy (n = 45), and excimer laser angioplasty (n = 24). Adjunct balloon angioplasty was used in 138 lesions (65%) and adjunct directional coronary atherectomy (after excimer laser angioplasty or rotational atherectomy) in

IMPACT OF ENDOVASCULAR STENTS

What happens when stents are used to treat coronary artery disease? We have performed serial IVUS analysis in 115 Palmaz-Schatz stents (Johnson & Johnson Interventional Systems, Warren, NJ). The quantitative analysis differs slightly from that in nonstented lesions, since the external elastic membrane is often not visible when a stent is in place. Arterial remodeling is defined as the change in stent (rather than external elastic membrane) cross-sectional area, while tissue growth is defined as

ADJUNCT PHARMACOLOGY

Pharmacologic approaches to reduce restenosis have focused on reducing cellular proliferation. The fact that drug therapy has been unsuccessful in nonstented lesions may be attributed to selection of the wrong target,[11]since serial IVUS studies have shown that restenosis in nonstented lesions is primarily due to arterial remodeling, not cellular proliferation. On the other hand, we now have a clinically important model of restenosis that represents pure neointimal tissue proliferation—i.e.,

VALUE OF IVUS ANALYSIS

Thus, IVUS can be of value in separating late lumen loss into 2 components: arterial remodeling and tissue growth. It can also be used to detect device-specific mechanisms of restenosis—i.e., exaggerated arterial remodeling following directional coronary atherectomy and exaggerated neointimal tissue proliferation following stent implantation.

Serial IVUS can be used to study the time course of remodeling. For example, the SURE trial shows that remodeling is biphasic, with early adaptive

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

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