Coronary CTA Findings Predict Mortality Risk, or Lack Thereof

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Coronary CT angiography (CTA) may be useful in patients without known coronary artery disease (CAD) to stratify mortality risk as well as identify those in whom further additional testing and/or therapy is not warranted, according to a large international registry published in the August 16, 2011, issue of the Journal of the American College of Cardiology.

For the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry) study, researchers led by James K. Min, MD, of Cedars-Sinai Medical Center (Los Angeles, CA), evaluated 24,775 consecutive patients without known CAD who underwent coronary CTA for suspected coronary disease at 12 centers between 2005 and 2009.

In the per-patient analysis, obstructive and nonobstructive CAD (50% stenosis threshold) conferred increased risk of mortality compared with patients without evident CAD. In a per-vessel analysis, incident mortality showed a dose-response relationship to the number of coronary vessels exhibiting obstructive CAD, with increasing risk observed for nonobstructive, obstructive 1-vessel, 2-vessel, or 3-vessel or left main disease (table 1).

Table 1. Per-Patient and Per-Vessel Analysis: CAD vs. Normal Arteries

Similarly, per-segment analysis found higher rates of mortality were associated with greater numbers of segments with plaque, stenosis-adjusted segments with plaque, any severe proximal stenosis, and any plaque within the left main.

Absence of CAD detection on coronary CTA was associated with a low annualized rate of incident death (0.28%).

Although risk of all-cause death rose for patients aged 65 years and older with extent and severity of CAD, younger patients (< 65 years of age), in comparison, had a marked increase in risk of death associated with 2- and 3-vessel or left main CAD compared with those who had no signs of CAD (table 2).

Table 2. All-Cause Death: CAD vs. Normal Arteries

Compared with men, women had higher estimated pre-test probability of CAD, yet lower rates of both obstructive and nonobstructive CAD on coronary CTA. However, they experienced higher hazard ratios for mortality for 3-vessel or left main obstructive CAD and had similar rates of death for nonobstructive, 1-vessel, and 2-vessel disease.

Results Can Inform Guidelines, Appropriate Use Criteria

According to the study authors, CONFIRM had sufficient sample size and was adequately powered to allow differential risk stratification by age group and sex. Therefore, the data extend prior studies and are “widely generalizable,” they say, especially since the international cohort encompassed patients and clinical sites within North America, Europe, and Asia.

“That [coronary CTA] can effectively risk stratify individuals without known CAD should be invaluable for guiding the development of clinical practice guidelines and appropriate use criteria,” Dr. Min and colleagues write.

As to the differences between women and men undergoing coronary CTA, the investigators note that the generally lower prevalence of disease in women has been historically associated with lower rates of invasive coronary angiographic evaluation and often leads to exclusion of cardiac causes of symptoms in women, despite being more likely to be hospitalized for angina than men.

“It remains possible in this open-label study that the identification of nonobstructive noncardiac diagnoses for symptoms, and lack of aggressive treatment for these CAD findings resulted in heightened risk of incident death,” they write. “Future studies should carefully evaluate this potential explanation and should determine the effect of primary prevention with aggressive medical therapy in this cohort.”

The age differences may be related to younger patients with greater extent and severity of CAD having more aggressive forms of atherosclerosis than their older counterparts, thus resulting in a higher mortality risk than older patients with more insidious atherosclerosis, the study authors add.

Importantly, they point out that the low death rate in patients without CAD on coronary CTA “validates the favorable prognosis that has been uniformly observed in prior smaller registries and emphasizes a clinical value of [coronary CTA] for identification of individuals in whom no further additional testing and/or therapy is necessary or indicated.”

Importance of Linking Anatomy to Outcomes

In an editorial accompanying the study, Bernard De Bruyne, MD, PhD, and Carlos Van Mieghem, MD, PhD, of the Cardiovascular Center Aalst (Aalst, Belgium), report that the sample size of CONFIRM is almost 1 order of magnitude larger than all previous studies on coronary CTA-related outcomes and focuses on “the hardest possible endpoint.” Further strengthening the results, they conclude, is that selection bias is unlikely since more than 90% of patients had low or intermediate pre-test likelihood of CAD.

But Drs. DeBruyne and Van Mieghem caution that while the likelihood of finding some degree of atherosclerosis on coronary CTA is high, it has long been recognized that how the arterial lumen appears on angiography does not necessarily indicate function or effect on myocardial blood flow. In other words, anatomy is only one of many factors that define symptoms and prognosis.

“Nevertheless, the visual impression of the luminogram and the sacred threshold of 50% diameter stenosis remain pivotal to the very definition of the presence of coronary artery disease; for the description of its extent in 1-, 2-, or 3-vessel disease; and constitute the basis for the vast majority of individual clinical decisions regarding revascularization,” they write.

The challenge for clinicians, according to the editorialists, is to properly integrate anatomy and function in the same setting to aid in diagnosis and treatment. Another area that holds promise for doing just that is the use of noninvasive fractional flow reserve (FFR), which involves calculating FFR from patient-specific coronary CTA data using computational fluid dynamics during rest and simulated maximal coronary hyperemic conditions.

“If cardiac imaging is to affect the individual clinical decision-making process, it must reconnect us with a basic foundation of cardiology that is, in fact, physiology,” they write.

Study Details

The study cohort was primarily male (54%) and middle-aged (57 ± 13 years), with a high prevalence of cardiovascular risk factors and symptoms. The majority presented with typical or atypical angina and intermediate or high pre-test likelihood of obstructive CAD.

 

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Sources:
1. Min JK, Dunning A, Lin FY, et al. Age- and sex-related differences in all-cause mortality risk based on coronary computed tomography angiography findings. Results from the international multicenter CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry) of 23,854 patients without known coronary artery disease. J Am Coll Cardiol. 2011;58:849-860.

2. De Bruyne B, Van Mieghem C. Coronary computed tomography angiography: CONFIRMations and perspectives. J Am Coll Cardiol. 2011;58:861-862.

 

 

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