CT Puts a Positive Spin on Coronary Remodeling

But without symptoms, and without a proven screening technique, hundreds of thousands of unsuspecting victims won’t be diagnosed.
Kim Phelan


May 23, 2006
Photo courtesy of Toshiba America Medical Systems Positive remodeling is the most frequent cause of

In the microscopic world of arterial plaque, the only positive thing about positive remodeling is that physicians can visualize it — now noninvasively with multislice detector computed tomography (MDCT) — and treat it before it strikes with deadly force. But early detection of positively remodeled plaque, or the atherosclerotic thickening of vessel walls with outward expansion, is the ongoing challenge cardiologists face, even as 1.2 million Americans suffer a new or recurrent coronary attack each year.

What differentiates the dangerous condition of positive remodeling from negative remodeling (atherosclerotic thickening with inward constriction and stenosis), is its figurative silence. Positive remodeling produces no symptoms, no angina to signal a forthcoming cardiac event, which creates something of a blindfold for physicians in their determination of which patients to evaluate.

“With positive remodeling, there are usually no premonitory signs. This is why people have myocardial infarctions out of the blue without any warning,” said Edward Shapiro, M.D., professor of Medicine at John Hopkins University School of Medicine and director of noninvasive cardiac imaging, Johns Hopkins Bayview Medical Center. “This explains why you can have a negative stress test and then have a heart attack the next day. It’s because with a plaque that is positively remodeled you don’t have any problems with limitations to blood flow. What precipitates the event is a sudden rupture of the plaque. Once it ruptures and causes clots to form, only then does it obstruct blood flow.”

The association of vulnerable plaque with positive remodeling raises the stakes another notch for unsuspecting patients — unstable or vulnerable fibrofatty plaque is covered by a thin fibrous rim; internal hemorrhage in the plaque can result in acute expansion and sudden development of critical lumen stenosis associated with a coronary artery thrombosis, according to Dennis Foley, M.D., chief of Digital Imaging and professor of Radiology at the Medical College of Wisconsin in Milwaukee.

“This explains why 30 percent of patients who suffer from a myocardial infarct (MI) have no preceding symptoms,” said Dr. Foley.

Doctors Shapiro and Foley are among a growing number of physicians who are encouraged by the promise of CT in detecting the occurrence of and link between positive remodeling and vulnerable plaque.

A Viable Alternative?

Literature that supports the use of CT in detecting arterial remodeling is beginning to accrue. In clinical research titled “Assessment of coronary remodeling in stenotic and nonstenotic coronary atherosclerotic lesions by multidetector spiral computed tomography,” led by Stephan Achenbach, M.D., and published in JACC 2004, 43: 842-847, investigators noted that while available data is limited and further study will be required to determine the clinical applicability of MDCT (as well as magnetic resonance), the noninvasive nature of this imaging method makes it “an attractive candidate for further development, especially when the cost and risk of IVUS, the current standard, are considered.”

As the Achenbach article notes, intravascular ultrasound (IVUS) is currently the gold standard method for detecting positive remodeling and visualizing vulnerable plaque. But IVUS is extremely invasive, more so even than catheterization, which is why a noninvasive alterative is so appealing.

“Cardiac CT will have an enormous impact on those patients with undiagnosed coronary artery disease,” said Bruce Lachterman, M.D., medical director for the Cardiac Catheterization Laboratories at Houston Northwest Medical Center and St. Luke’s Community Medical Center, The Woodlands. In a printed Q&A discussion produced by Toshiba Medical Systems (see sidebar, p. 32), Dr. Lachterman said CT enables disease detection beyond coronary artery stenosis.

“Cardiac CT is a breakthrough technology, and I believe it will become the gold standard for cardiac disease detection,” he said.

Adding to that discourse, Steven Gunberg, D.O., clinical assistant professor at University of Colorado Health Sciences Center, reports that CT takes visualization of the vessel wall and plaque characterization to a new plane.

“The 64-slice detector cardiac CT enables us to visualize evolving plaque, or plaque considered vulnerable, far more easily than conventional coronary angiography,” said Dr. Gunberg. “We’re also able to see changes in the coronary vessels during the procedure and follow those changes more accurately than before.”

Vulnerable Connection

Researchers at the University of California, Irvine, School of Medicine, led by Jagat Narula, M.D., highlight the importance of multislice CT (MSCT) in allowing characterization of the composition of plaques, and, perhaps most significant, detection of the large necrotic core, which the team says “is becoming the sine qua non of plaque vulnerability.”

In an article titled, “Picking Plaques That Pop,” the group asserted that progressive enlargement of the necrotic core is associated with [a plaque’s] vulnerability to rupture. It concluded that MSCT should be able to identify large necrotic cores and outward [or positive] remodeling.

“Arterial remodeling of the vessel wall is the most important marker that can set the MSCT apart from angiography since the vessel wall can be easily observed,” the article states.

The connection between positive remodeling and vulnerable plaque is an accepted relationship — where positive coronary remodeling is found, vulnerable, soft plaque is likely to be present, and this is predominantly true in patients who have risk factors for cardiac disease but who have not yet developed clinical manifestations, according to Dr. Shapiro at John Hopkins.

“If you look at the microscopic content of the plaque that is positively remodeled, they contain more inflammatory cells and more lipids,” he said. “Those are known to be markers of plaque instability. The remodeling plaques have features that make them unstable.”

Dr. Shapiro also states that positive remodeling is more prevalent than negative remodeling, and the more common cause of MIs.

Too Soon for Certainty

Despite the promise of CT as a tool to identify positively remodeling vessels, sources are quick to add an important disclaimer to their endorsements. And that, fundamentally, is the absence of clinical evidence — via multicenter randomized trials — to verify the efficacy of cardiac CT in identifying positive remodeling and vulnerable plaque.

“So far, the ability and accuracy of MDCT to determine the extent of coronary remodeling have not been evaluated,” states a portion of the Achenbach discussion.

Many institutions are currently involved in trials to achieve this end, including Johns Hopkins, said Dr. Shapiro. But until results from these studies are available, he says it would be premature to assume that CT can replace IVUS in plaque detection and characterization.

“There are no scientific data yet proving that CT detection is worthwhile, just because it is new,” said Dr. Shapiro. “That is going to require plenty of study. And screening asymptomatic patients will be problematic until CT delivers less of a radiation dose. You shouldn’t subject populations to radiation without proof of efficacy, so screening of asymptomatic people is not yet recommended.”


Stopping a Silent Killer: How Doctors Treat Positive Remodeling
In the fortunate case in which positive remodeling is detected prior to its only outward symptom — sudden death by MI — physicians can impede the outward expansion of the vessel wall through aggressive medical therapy, which may include statin therapy, rather than revascularization.
“The expectation,” according to Dr. Dennis Foley, “is that vulnerable plaque will become progressively more fibrotic over time, gradually calcify and not be subject to sudden internal hemorrhage.”
Dr. Edward Shapiro adds that using IVUS to measure the positive remodeling, physicians should initiate aggressive lipid management to prevent the progression of positive remodeling, and in some cases, this treatment path is efficacious in promoting regression.

How Effective is Cardiac CT?
Physicians Speak Out
(Excerpts from a roundtable Q&A by Toshiba Medical Systems)
Introduction: We asked physicians for their views on 64-[slice] detector cardiac CT technology in routine practice and how cardiac imaging might be advanced in the future.

Recent statistics indicate that more than 300,000 Americans annually suffer from heart disease, with their first symptom being a heart attack or even sudden death. How do you think cardiac CT will impact these patients?
Dr. Bruce Lachterman: (continuing his response quoted on p. 31) With the ability to detect diseases beyond coronary artery stenosis, which is what other modalities detect, we now have the opportunity to detect cardiac disease at an early state to treat and prevent a broader spectrum of cardiovascular events. CT is a breakthrough technology, and I believe it will become the gold standard for cardiac disease detection.
Gerald Burma, M.D., Ph.D., cardiologist, Cardiovascular Clinic (Parma, OH): Calcium scoring will play a significant role in identifying patients with high-risk coronary artery disease. While screening will not identify disease in all patients, it may prove effective in 75 percent of the at-risk population. A certain percentage will seek medical intervention, but at least those patients will be made aware of their disease and its symptoms.
Steven Gunberg, D.O., clinical assistant professor at University of Colorado Health Sciences Center (Denver, CO): Certainly the impact of cardiac CT cannot be underemphasized. With this new technology, we can rapidly conduct cardiac procedures and triage patients more quickly to assess low probability or indeterminate probability for a cardiac event.
Ron Peshock, M.D., Ph.D., professor of Radiology and Internal Medicine and assistant dean for Informatics, University of Texas Southwestern Medical Center at Dallas: Identifying at-risk patients and preventing problems in those who don’t present symptoms prior to death or their first attack is obviously vital. It’s important to point out the potential role that cardiac CT could play here. There are a number of clinical studies on the horizon that may clarify the role of cardiac CT in addressing these types of patients.

How important is the ability to accurately visualize the vessel wall and characterize plaque?
Peter Fail, M.D., director of Cardiac Catheterization Lab and Interventional Research, Cardiovascular Institute of the South (Houma, LA): This is an important clinical benefit because if we can image arteries before they reach 50 percent blockage, we can be fairly comfortable that the vessel wall will not rupture and be less concerned about patients with thin, fibrous plaque or what looks to be a vulnerable lesion. Cardiac CTs may help us image noninvasively, with a high degree of accuracy, for 50 to 60 percent blockage of vulnerable plaque that has a chance of rupturing — which may not be angiographically impressive, but is histologically impressive. We may be able to intervene early with a drug-eluting stent much more aggressively to prevent the plaque from rupturing and endangering the life of the patient.
Dr. Burma: It’s very important to identify calcified plaque as well as soft plaque. Higher soft plaque burden, as opposed to calcified plaque burden, correlates to a higher risk and adverse event rate. In the near future, we might see the development of a cardiac CT with algorithms able to assess the amount of soft plaque that is visible through CT angiography.