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IVUS sees lumen wall's interior in atherosclerosis. (Thinking Systemic).

CHICAGO -- Intravascular ultrasound is prompting interventional cardiologists to rethink their models of atherosclerosis as well as the value of the angiographic tools that have been the mainstay of diagnosis and evaluation for this disorder.

"Atherosclerosis is a systemic disease. If one site in the coronary tree is angry, you can bet that multiple sites are as well," said Dr. E. Murat Tuzcu, director of intravascular ultrasound (IVUS), Cleveland Clinic Foundation.

Unfortunately, angiography is a site-specific diagnostic method that detects only those coronary artery segments in which there is significant lumen narrowing. Angiograms are really "lumenograms, Dr. Tuzcu said. They show what is happening on the vessel walls, but they reveal little about what is going on within the vessel walls, where the disease process occurs.

Speaking at the annual meeting of the American Association of Clinical Endocrinologists, he stressed that "nonobstructive disease is not necessarily mild, and a normal angiogram is not necessarily normal." IVUS allows for imaging of the vessel-wall intima, and often reveals bulky atheromas, calcification, and fibrous or lipotic depositions in angiographically normal vessel segments.

He and his colleagues are studying IVUS in the evaluation of treatment response to aggressive versus moderate-intensity lipid-lowering drug therapy. The ongoing study involves 600 patients randomized to a variety of different regimens. "We have no doubt that atherosclerosis can regress," Dr. Tuzcu said, noting that in one case, he observed a plaque of 10 [mm.sup.2] regress to 3 [mm.sup.2], though angiography showed no differences.

"The serial nature of IVUS is probably the most valuable aspect. You can evaluate the same vessel in total over time, and see the areas of change. IVUS findings correlate very well with actual histologic features," he said.

Dr. Tuzcu and his colleagues at the Cleveland Clinic have been working with bioengineers to develop a clinically practical system for intravascular "sonohistology."

"You can get real-time histology as you move the probe through the arteries. Hopefully, this will improve the detection of angiographically invisible lesions."

To understand the gap between angiography and IVUS, one needs to understand that there are two general patterns of vascular remodeling. In "positive" or expansive remodeling, the vessel wall accommodates the atheroma by expanding outwardly, away from the lumen, thus maintaining lumenal diameter. In negative or constrictive remodeling, the vessel wall grows into the lumen, producing areas of stenosis.

The ratio between the diameter of a so-called culprit lesion and a reference-segment is termed the remodeling index. If the ratio of culprit to reference is greater than 1, the site is showing positive remodeling; if the ratio is less than 1, the pattern is negative.

Histologically and clinically, positive and negative remodeling are quite distinct. Positive remodeling is the more common pattern in patients with unstable angina and coronary artery syndrome, and these lesions tend to show a lot of staining with matrix metalloproteinase-3 (MMP-3). Negative remodeling is typically associated with stable angina, and these lesions do not stain with MMP-3.

Angiographically, the positive remodeling pattern is often undetectable because the lumen diameter is preserved. This is particularly true if the atheroma is eccentric. An angiogram best detects segments in which negative remodeling and vessel stenosis has occurred. But the absence of stenosis does not mean the absence of risk for plaque rupture and thrombosis.

Dr. Tuzcu pointed out that angiographic assessment of atherosclerotic lesions is based on an inherent assumption that the external elastic membrane area in the so-called reference segment is representative of the original vessel size at the lesion site. IVUS is challenging that assumption.

"All comparative studies of atherosclerotic coronary arteries have demonstrated that angiographic reference segments are invariably diseased when studied with intracoronary ultrasound," he said.

This is particularly true among diabetics, in whom 80% of all mortality is related to cardiovascular disease. Dr. Tuzcu and his colleagues have used IVUS in the evaluation of hundreds of diabetic patients. "They have very, very diffuse disease. With angiography we look at 'normal' versus adjacent reference sites. But when you look inside, the pipes are anything but normal. The atherosclerosis is so widespread, there really is no normal [nonatherosclerotic] reference site," he said.

Vessels in diabetics are less able to accommodate atheromas by positive remodeling. Rather, they show negative remodeling, followed by vessel wall shrinkage around the lesion sites, ultimately resulting in stenosis.

Diabetics also show less vascular compliance, even if there is no atherosclerosis.

In a recent physiologic experiment, nonatherosclerotic vessel segments obtained from nondiabetics showed smooth and progressive expansion with increasing infusion pressure. Similar vessel samples obtained from diabetics of the same age showed markedly less expandability in response to pressure increases.

IVUS is also confirming that atherosclerosis begins in childhood. Dr. Tuzcu reported data from a study of 262 individuals requiring heart transplants primarily for congenital anomalies. The cohort induded a large number of children and adolescents.

Preoperative IVUS assessment of the coronary arteries revealed that 17% of teenagers and 37% of those aged 20-29 have IVUS-detectable atheromas (Circulation 103[22]:2705-10, 2001). Not all young people with atheromas will develop CAD later in life, "but you can bet that all of the people who have CAD in their 50s, 60s, and 70s will come from this cohort," Dr. Tuzcu said.
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Title Annotation:intravascular ultrasound
Author:Goldman, Erik L.
Publication:Internal Medicine News
Article Type:Brief Article
Date:Jul 1, 2002
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