Angiograms Miss Most Atheromas.
Massive atheromas lurking within the vascular wall--outside the view of angiography--are the lesions that account for the two-thirds of mocardial infarctions that occur at sites with "hemodynamically insignificant stenosis."
"This is a painful lesson for my colleagues in interventional cardiology. They don't like [to be told] they're looking at the wrong end point" when they give patients with a normal angiogram a clean bill of health, said Dr. Nissen, head of clinical cardiology at the Cleveland Clinic.
To demonstrate his point, Dr. Nissen showed on one screen an "absolutely normal" angiogram of a left anterior descending coronary artery. Turning to a second screen, he displayed a miniature intravascular ultrasound (IVUS) image of the same artery The "perfectly shaped, normal-sized" lumen was surrounded by adventitia containing huge, crescent-shaped atheromas.
"I can tell you today, after a decade of looking at these arteries [with IVUS], [the angiographic] model of coronary artery disease is dead wrong," he said. "Coronary artery disease is not an intraluminal disease. It is an extraluminal disease."
Dr. Nissen's assertions would explain why interventional cardiology procedures relieve angina but do not reduce the risk of mortality from future myocardial infarctions. They also explain why lipid-lowering drugs reduce cardiovascular event rates, even though they do not dramatically improve coronary angiography findings.
And they challenge the 40 years of conventional wisdom that heart disease is primarily a plumbing problem, Dr. Nissen said. Atherosclerosis "was thought to produce all of its morbidity and mortality by virtue of luminal narrowing. In fact, we now know that's not true. The plaque, the atheroma in the wall of the artery is the critical factor that determines the natural history and pathophysiology in coronary disease."
IVUS findings appear to verify the theories of Dr. Seymour Glagov of the University of Chicago, who proposed nearly 15 years ago that plaque-filled adventitia remodels outward, causing no distortion in the size or shape of the lumen until the disease is quite advanced.
Dr. Nissen's presentation demonstrated that phenomenon in patients young and old, all of whom were in sound cardiac health based on conventional testing. "Not only was Glagov right, but I'm going to show you that 95%-99% of all coronary disease looks like [this]," he said.
IVUS, developed about 10 years ago and now available in major medical centers, provides real-time, cross-sectional images of the entire arterial wall. A catheter less than 1 mm in diameter is passed through a single artery Rotating at 1,800 rpm, the IVUS catheter sends and receives ultrasound at a frequency of 30 MHz. The images provide a view once seen only at autopsy of the intima, the endothelium, the media, and the external elastic membrane where the adventitia begins. Most atherosclerosis forms in the external layers of the artery wall.
"If you look for the disease with a stress test, if you look for it with an angiogram, you do not see the disease here, here, or here," he said, pointing to ominous atheromas filling the external elastic membrane of an otherwise healthy 32-year-old patient whose heart was transplanted after her death in a car accident. "The Titanic got to see 16% of the iceberg that destroyed it. As cardiologists with angiography, we only get to see 1% of the disease ... that kills half the population and 80% of all diabetics."
In autopsy evaluations of 262 heart transplant donors studied by Dr. Nissen and his associates, atherosclerosis was found by IVUS in 17% of donors younger than 20 years old, in 37% of those in their 20s, in 60% of those in their 30s, in 71% of those in their 40s, and in 85% of those in their 50s.
These cases included a 33-year-old accident victim who had 4 mm of extraluminal atherosclerotic plaque in his left anterior descending artery and a 17-year-old gunshot victim with significant plaque in his left anterior descending artery Both had dear angiograms.
In a study of patients undergoing interventional cardiology procedures, Dr. Nissen asked the patients' interventional cardiologists to select an arterial location that represented "the most normal site he could find." Atherosderotic plaque occupied 40% of the external elastic membrane area.
Body mass index and smoking were the most predictive factors of extraluminal plaques in autopsy cases. "When you see patients at middle age with type 2 diabetes, they very likely have extensive atherosclerotic disease, regardless of what ancillary testing might show," he said.
Dr. Nissen said metabolic therapy addresses the types of plaque visualized by IVUS. In a "natural history experiment," he and his colleagues at the Cleveland Clinic showed that extraluminal plaques regressed by as much as 2 [mm.sup.2] when atherosderotic donor hearts were transplanted into recipients without atherosderotic disease.
The same dynamic is at work when drugs change the "atherosderotic milieu," he said. "Stabilization of unstable atheromas is an attainable goal."
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|Publication:||Family Practice News|
|Article Type:||Brief Article|
|Date:||Jul 15, 2001|
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