Meta-analysis Supports CTA’s Predictive Value

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The presence and extent of coronary artery disease (CAD) on cardiac computed tomographic angiography (CTA) strongly predicts the likelihood of cardiovascular events in symptomatic patients, according to a meta-analysis that appears in the June 14, 2011, issue of the Journal of the American College of Cardiology.

Fabian Bamberg, MD, MPH, of Ludwig-Maximilians University (Munich, Germany), and colleagues searched PubMed, EMBASE, and the Cochrane Library through January 2010. Out of approximately 650 potentially relevant articles, they identified 11 studies (n = 7,335) using CTA that each followed at least 100 subjects with suspected or known CAD for at least 1 year and assessed cardiovascular events. Most studies were single-center (82%) and conducted in Europe or the United States. Median follow-up duration was 20.4 months.

Strong Findings Despite Mixed Bag of Studies

Substantial heterogeneity existed for the CT findings reported, outcomes measured, and type of CT technology used: 7 studies employed 64-slice CT, 2 used 16-slice CT, and 2 used electron-beam CT.

In all, 9 studies analyzed a combined cardiovascular endpoint—including all-cause mortality, cardiovascular mortality, nonfatal MI, unstable angina requiring hospitalization, and revascularization—and also estimated risk for that endpoint based on the presence of significant CAD. Revascularization represented 62% of all 252 outcome events documented by the meta-analysis. The remaining 2 studies contained no data on revascularization.

Patients found to have at least 1 significant coronary stenosis experienced an elevated risk of cardiovascular events. The risk was higher when studies included revascularization (table 1). Notably, adjustment for coronary calcification did not diminish the prognostic significance of CTA (P = 0.79).

Table 1. Cardiovascular Event Risk in Patients with ≥ 1 Significant Coronary Stenosis


Annualized Event Rate

HR (95% CI)

With Revascularization


10.74 (6.37-18.11)

Without Revascularization


6.15 (3.22-11.74)

Several other CT findings also were shown to predict the risk of cardiovascular events (table 2).

Table 2. Cardiovascular Event Risk in Patients with Secondary Predictors



95% CI

Left Main Stenosis



Three-Vessel Disease



Presence of Any Plaque



Each Segment Containing Any Plaque



Each Segment Containing Noncalcified Plaque




In light of the extreme heterogeneity they found among CTA studies, Dr. Bamberg and colleagues urge that future research should include standard reporting of the following endpoints:

  • Presence of at least 1 coronary artery stenosis (≥ 50%) per patient
  • Number of coronary segments containing at least 1 coronary artery stenosis (≥ 50%)
  •  Left main CAD
  • Presence of any detectable atherosclerotic plaque (regardless of severity) per patient
  • Number of segments containing any nonobstructive plaque (calcified, noncalcified, and mixed plaque)

More than a Way to Rule Out CAD

Dr. Bamberg told TCTMD in an e-mail communication that CTA is known to be highly accurate in detecting CAD and thought to improve management of distinct patient populations, such as those presenting with acute chest pain.

“Our analysis summarizes available smaller studies and reveals that cardiac CTA findings also have very strong prognostic value for the occurrence of events in the long run,” he noted. “Thus, cardiac CTA has diagnostic and prognostic implications for patient management, a fact that has not been so evident to date and certainly not been considered in ongoing discussions about the value of the technique.”

Speaking with TCTMD in a telephone interview, Michael Poon, MD, of Stony Brook University Medical Center (Stony Brook, NY), agreed. “Right now, people only think of the ability of CTA to rule out coronary artery disease,” he said. “This study adds to [what we know about] positive CTA findings. [The test is] important because it predicts adverse coronary events. The more coronary involvement, the more at risk you are.”

In short, Dr. Poon commented, the meta-analysis should not lead clinicians to use CTA more often but instead will change how they apply the results. CTA can be thought of “not only as a test for excluding coronary artery disease but also, if it’s positive, you should be very careful and take more precautions, [meaning] more lifestyle modifications and medications,” he explained.

Because there has not yet been research comparing the prognostic value of CTA with validated and widely used tests, such as myocardial perfusion imaging or serum biomarkers, said Dr. Bamberg, “at this point our analysis will rather change how clinicians apply cardiac CTA results in practice by providing prognostic information beyond the diagnostic findings at no extra cost. Notably, I also think that our data demonstrate that cardiac CTA has become one of the potential key players in the field of cardiovascular risk assessment.”

Robert S. Schwartz, MD, of the Minneapolis Heart Institute (Minneapolis, MN), also commented to TCTMD in a telephone interview that the paper “ties together the little studies to make the big picture strong.”

But he also took away another message: the importance of vulnerable plaque and calcium. “That’s why this meta-analysis is important, because it says that people who have . . . bad things happening in their arteries [are likely to] have bad events and those have an effect on prognosis,” Dr. Schwartz concluded.

Much of the emphasis in today’s clinical practice is on measuring cholesterol levels, Dr. Schwartz noted, but CTA may provide different and more useful prognostic information. “Half of all heart attacks occur in patients with normal cholesterol,” he reported.

Another hot area of research is noninvasive fractional flow reserve, which is derived from CT measurements. “That’s going to be a big story if that pans out well,” predicted Dr. Schwartz, who is leading the core lab of HeartFlow (Redwood City, CA), the company developing the technology. “But we have to wait for the data, of course.”

Going Beyond Calcium Scoring

Dr. Poon highlighted a point made in the paper’s discussion: that the approximately 10-fold increased risk imparted by significant coronary stenosis mirrors, perhaps coincidentally, the estimated risk associated with an Agatston score of at least 400 found by a previous meta-analysis (Pletcher MJ. Arch Intern Med. 2004;164:1285-1292). The similarity would seem to indicate that calcium scoring and CTA hold similar prognostic value.

However, Dr. Bamberg pointed out, “there is much more level of detail to the extent of coronary artery disease on CTA, which appears to be independent of the calcium score.”

CTA has the ability to identify vulnerable, noncalcified plaque, “whereas calcium scores only show you the calcified plaque,” Dr. Poon explained. “If you have a calcium score of 400 or more, the reason why you’re so high risk is because you [also] have a lot vulnerable plaque. Even if you don’t see it, it’s there [and could be visualized with CTA]. This study affirms that.”


Bamberg F, Sommer WH, Hoffman V, et al. Meta-analysis and systematic review of the long-term predictive value of assessment of coronary atherosclerosis by contrast-enhanced coronary computed tomography angiography. J Am Coll Cardiol. 2011;57:2426-2436.



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Caitlin E. Cox is News Editor of TCTMD and Associate Director, Editorial Content at the Cardiovascular Research Foundation. She produces the…

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  • Dr. Bamberg reports having received grant support from Siemens.
  • Dr. Poon reports serving on the speakers’ bureau for Toshiba.
  • Dr. Schwartz reports no relevant conflicts of interest.