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Slide 1

As initially reported by Ambrose et al.¹ and Little et al.², the risk of coronary occlusion is not proportional to the prior severity of coronary stenoses. In fact, coronary occlusion and myocardial infarction most frequently evolve from plaques that are only mildly to moderately obstructive³. The culprit lesions turned out to be in 70% of the cases consequence of disruption of a less than 50% stenotic lesion. Therefore, angiography does not allow the identification of patients at high-risk for acute coronary events.

Slide 2

Glagov observed⁴ that in the early stages of atherosclerosis - as consequence of compensatory outward enlargement (positive remodeling) - plaques might progress without compromising the lumen. Using serial MR imaging we have shown features of arterial remodeling in several animal model of atherosclerosis (such as Watanabe Heritable Hyperlipidemic rabbits)⁵. Additionally, significant atherosclerosis despite normal or ectatic coronary arteries have been recently documented in vivo using noninvasive black-blood MR imaging⁶.
The figure indicates: In vivo MR cross-sectional images of coronary arteries demonstrating a plaque presumably with deposition of fat (arrow, A) and a concentric fibrotic lesion (B) in the left anterior descending artery as well as an ecstatic, but atherosclerotic, right coronary artery (C). RV indicates right ventricle, LV indicates left ventricle.

Slide 3

Imaging of the aortic atherothrombotic disease.
Aortic in vivo MR image from a patient with a 4.5-mm thick plaque in descending thoracic aorta (A) and corresponding TEE image (B). MR image shows an example of a plaque with a dark area in the center (arrow) identified on the T2W image as a lipid-rich core (A). Lipid-rich core is separated from lumen by a fibrous cap.

Slide 4+5


We have used MR to measure the effects of lipid-lowering therapy (statins) in asymptomatic untreated hypercholesterolemic patients with carotid and aortic atherosclerosis ⁷. Atherosclerotic plaques were assessed with MR at different time points after initiation of lipid-lowering therapy. Significant regression of atherosclerotic lesions was observed. Importantly, despite the early and expected hypolipidemic effect of the statins, a minimum of 12 months was needed to observe changes in the vessel wall. No changes were detected at 6 months. There was a decrease in the vessel wall area in both carotid and aortic plaques, but no change in the lumen area at 12 months, in agreement with previous experimental studies ^5,8. The significant reduction in lesion size without affecting the lumen seems to be mediated by reduction in the plaques, lipid content and thus indicative of structural changes favoring their stabilization.

Slide 6

Gallo et al demonstrated that in the porcine coronary arteries inhibition of intimal thickening after balloon angioplasty was achieved by treatment with rapamycin (targeting at the regulators of the cell cycle). The figure displays Representative histological sections corresponding to control (right) and rapamycin-treated (left) animals.

References

1. Ambrose JA, Tannenbaum MA, Alexopoulos D, et al. Angiographic progression of coronary artery disease and the development of myocardial infarction. J Am Coll Cardiol. 1988;12:56-62.
2. Little WC, Constantinescu M, Applegate RJ, et al. Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease? Circulation. 1988;78:1157-1166.
3. Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation. 1995;92:657-671.
4. Glagov S, Weisenberg E, Zarins CK, et al. Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med. 1987;316:1371-1375.
5. Worthley SG, Helft G, Fuster V, et al. Serial in vivo MRI documents arterial remodeling in experimental atherosclerosis. Circulation. 2000;101:586-589.
6. Fayad ZA, Fuster V, Fallon JT, et al. Noninvasive in vivo human coronary artery lumen and wall imaging using black-blood magnetic resonance imaging. Circulation. 2000;102:506-510.
7. Corti R, Fayad ZA, Fuster V, et al. Effects of lipid-lowering by simvastatin on human atherosclerotic lesions: a longitudinal study by high-resolution, noninvasive magnetic resonance imaging. Circulation. 2001;104:249-252.
8. Worthley SG, Helft G, Osende JI, et al. Serial Evaluation of Atherosclerosis with in Vivo MRI: Study of Atorvastatin and Avasimibe in WHHL Rabbits. Circulation. 2000;102:II-809.