Vulnerable Plaques

Coronary heart disease, acute coronary syndrome and angina pectoris are the leading cause of mortality in the United States. Annually, 451000 people die from these diseases, 800000 suffer acute MI and 156000 died from an MI, and many more are hospitalized due to an acute manifestation of ischemic heart disease. The personal, social and economic consequences are enormous, for 2008 they are estimated at 156.4 billion annually in the United States alone [31]. 

In vivo identification of plaque eomposition with suffieient resolution should enable the detection of vulnerable plaque before rupture enabling some local treatment. Being able to image vulnerable plaques may lead to the detection of the eharacteristics of a vulnerable plaque that could allow the development of predietive models to assess the risk that a vulnerable plaque poses to the patient [33]. Current state-of-the-art IVUS systems, sueh as those that use VH from Volcano Corporation, do not measure the thin fibrous cap explicitly as the axial resolution is too poor to detect the thin caps. Rather, when a necrotic core is with in 125 microns of the lumen, it is assumed to be covered by a thin fibrous cap and is deemed vulnerable [29,51]. 

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Flacke S, Fischer S, Scott MJ, Fuhrhop RJ, Allen JS, McLean M, Winter P, Sicard GA, Gaffney PJ, Wickline SA, Lanza GM (2001) Novel MRI contrast agent for molecular imaging of fibrin implications for detecting vulnerable plaques. Circulation 104 1280-1285... 

T. Khan, B. Soller, M. Naghavi, and W. Casscells, Tissue pH determination for the detection of metabol-ically active, inflamed vulnerable plaques using near-infrared spectroscopy an in-vitro feasibility study. Cardiol. 103, 10-16 (2005). 

Kolodgie ED, Petrov A, Virmani R, Narula N, Verjans JW, Weber DK et al. Targeting of apoptotic macrophages and experimental atheroma with radiolabeled annexin V a technique with potential for noninvasive imaging of vulnerable plaque. Circulation 2003 108 3134-3139... 

Atherosclerosis The imaging of atherosclerosis with [ F]FDG PET was advanced and recent studies in rabbits showed that the tracer accumulated in macrophage-rich atherosclerotic plaques. It was assumed that the vascular macrophage activity can be quantified by p FlFDO PET [189]. Further studies in rabbits demonstrated that this imaging modality is useful for the clinical evaluation of therapeutic effects of drugs as well as for the development of new drugs that can reduce and inhibit inflammation of vulnerable plaques [190]. 

R. Virmani, A.P. Burke, F.D. Kolodgie, A. Farb, Pathology of the thin-cap fibroather-oma A type of vulnerable plaque, J. Interv. Cardiol. 16 (2003) 267-272. 

Yeung, A. (2004) Vulnerable Plaque Pathophysiology, Detection and Therapeutic Intervention, Cardiovascular Research Foundation 16th Annual Scientific Meeting of Transcatheter Cardiovascular Therapeutics (TCT), Washington, DC. 

ACS represents a prothrombotic state not just confined to the culprit lesion, with evidence of a pan coronary process and generalized platelet activation. Multiple vulnerable plaques in nonculprit vessels have been identified by angioscopy or intravascular ultrasound in ACS. Protracted treatment with clopidogrel induces antiplatelet activity that provides early benefits, and may limit thrombotic events within the following months. In the CURE study, the curves of major vascular events continue to diverge and showed an additional benefit from one-month follow-up to one year. 

Naghavi M, Libby P Falk E, et al. From vulnerable plaque to vulnerable patient a call for new definitions and risk assessment strategies Part I, Circulation 20037 108(14) 1664-1672. 

Virmani R, Burke AP Farb A, Kolodgie FD. Pathology of the vulnerable plaque, J Am Coll Cardiol 2006 47(suppl 8) Cl 3-0 8. 

The impact of early vulnerable plaque detection and therapy would be a major breakthrough in the management of patients with coronary, periperhal and neurovascular disease ... 

In the upper panel, a vulnerable plaque is demonstrated with thin fibrous cap, large lipidcore, and increased density of microphages. In the lower panel, a plaque rupture with accompanying thrombi is shown. 

The growing clinical interest of detection and treatment of the vulnerable plaques or patients opens a new area of investigation, The promise of using l7(3-estradiol on a DES platform as a prohealing strategy could potentially improve the clinical outcome in such high-risk populations. Because of the beneficial effects of l7(3-estradiol on vascular cells, this approach could offer patients a safer method of plaque stabilization. 

Antrin Motexafin lutetium Coronary PI Vulnerable plaque ... 

Vascular Mono-L-aspartyl vulnerable plaque Japan as... 

PhotoPoint (AX/ravanf) MV0633 Vulnerable plaque and coronary restenosis ... 

These authors felt that myloperoxidase was good for the prediction of ACS, because it is released by leukocytes, and is elevated and active in vulnerable plaques. It has also been mechanistically associated with factors that effect plaque development and stability. Myloperoxidase was independent... 

Characterization of Vulnerable Plaques by Near-Infrared Spectroscopy in the Atherosclerotic Rabbit, Amer. College Cardiol. 48th Annual Sci. Session, New Orleans, March, 1999. 

Figure 6.1 Different examples of (A) stable plaque, (B) vulnerable plaque, (C) eroded plaque with small thrombus and (D) ruptured plaque with occlusive thrombus. This figure can be seen in colour, Plate 5.

A hypothesis for vulnerable plaque rupture due to stress-induced debonding around cellular microcalcifications in thin fibrous caps. Proc Natl Acad Sci U S A 103 14678-14683... 

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