In this study, we demonstrate that coronary CTA in patients with acute chest pain substantially changes probability of ACS both for a negative and a positive test result (based on the presence of a 50% stenosis or inconclusive CT exams) in men <55 years of age and women <65 years of age. Moreover, applying these results to a risk classification scheme, demonstrates that coronary CTA leads to a restratification from low risk to high (for a positive CTA) or very low risk (for a negative CTA). Thus, coronary CTA might have the greatest clinical utility in women <65 years of age and men <55 years of age.
Several recent studies have demonstrated that coronary CTA may be helpful to guide management of patients presenting with acute chest pain in the ED, especially in the early triage of patients with low to intermediate likelihood for ACS where CT may facilitate early discharge. However, these studies report a wide range of ACS rates (0-34%) 1,2,4
, which suggests heterogeneity of the populations studied. In the analysis presented here, we demonstrate that the clinical utility of coronary CTA in the setting of acute chest pain appears to vary with age and gender even within a population of patients overwhelmingly classified as low risk according to the TIMI risk score (95%). This observation is based on differences in the prevalence of ACS, the prevalence of a significant stenosis in coronary CTA and the accuracy of this finding for identifying patients with ACS in age and gender specific strata.
Age and gender are well known strong predictors of CAD, myocardial infarction, and ACS9-11
. Consequently, we observed a significant increase of prevalence of ACS and significant CAD from 0 to 21% and 0 to 35% in women and 5% to 25% and 6% to 64% in men across age strata; respectively. Diagnostic accuracy of CTA for ACS was related to the prevalence of CAD (sensitivity range: 100 to 66.7% and 100 to 62.5% for women and men; respectively). Importantly, the observed difference of 10 years between women and men mirror exactly the gender difference which has been described previously with respect to intima media thickness or coronary artery calcification.13,14
Thus, our findings are consistent with the high accuracy for the detection of stenosis in populations with a low prevalence of CAD and the close association of CAD and ACS.15
While the ultimate assessment of clinical efficiency of a diagnostic test is performed within the framework of a cost-effectiveness analysis, changes in pretest probability within clinically accepted risk categories based on basic clinical and demographic variables are often used. Examples are the TIMI risk score in patients with unstable angina and non-ST elevation MI acute chest pain and suspicion for ACS16
, the Diamond and Forrester classification in patients with suspected CAD17,18
, and the Framingham Risk Score for asymptomatic patients.19
Definition of high, low or intermediate risk is usually arbitrary but reflects the severity and consequences of an event. For example, low risk is considered as <4% ACS in patients with acute chest pain12
, <30% significant CAD (>50%) in patients with suspected CAD20
, and <10% (Death or myocardial infarction) over 10 years (1% annually) in asymptomatic patients.21
In contrast to Meijboom et al. 20
, who based the pretest probability for CAD on the Duke score, we based pretest probability for ACS on the observed prevalence of ACS in each subgroup. This was necessary because 95% of our patient population was at low TIMI risk score and thus further stratification was not feasible. However, our results are consistent with those of Meiboom in that coronary CTA was not useful in patients with a high pretest probability.20
Instead, in women <65 years of age and men <55 years of age both a positive and negative test resulted in a change of the risk estimate either to very low (<1%) or high risk (≥16%) indicating the highest clinical utility. Most remarkable is that a finding of a significant stenosis in men <45 years of age carries an absolute increase of 70% in probability for ACS. Cost-effectiveness of coronary CTA, at least cost saving in younger patients, has been suggested by recent cost-effectivness analyses22,23
and a small randomized CT trial in patients with acute chest pain ($1,586 vs. $1,872, p<0.001).1
Overall, this is consistent with the notion that the clinical value of coronary CT is mostly derived from its ability to safely exclude significant coronary artery disease.24
Although our results indicate that a large portion of women <65 and men <55 years of age with a negative CT may be safely discharged without further testing, it remains to be determined whether re-stratification into very low risk or high-risk will consistently result in immediate and significant management decisions such as discharge (as suggested by Goldman et al.) or referral for invasive angiography, respectively. Such determination is typically done within registries or randomized trials.
In contrast, clinical utility in women older than 65 years and men older than 55 years of age cardiac CT may be low as the observed prevalence of significant stenosis by CT (>30%), ACS (>20%), and inconclusive coronary segments (>9%) is already high and coronary CT only results in restratification to intermediate/high risk. One explanation for this finding is that CAC, a known reason for low PPV of coronary CTA, becomes highly prevalent in this age group,.25
Thus, alternative testing modalities may be superior in triaging these patients.26
Our finding that women <45 years of age did not have any stenosis detectable in CT and did not develop any event deserves further comment. Primarily, this finding can be attributed to our limited sample size as it is known that in these subjects ACS occur. Moreover, these women were all admitted to the hospital as a standard of care and 28% underwent myocardial perfusion imaging (data not shown). Thus, cardiac CTA may prove beneficial in these subjects. However, associated radiation exposure with an increased risk in younger women warrants further research on the feasibility of low dose-CT protocols (<5 mSv) and subsequent risk-benefit analysis of CT imaging in these younger females.
The major limitation is the low number of events within subgroups, resulting in wide confidence intervals. However, ROMICAT currently is the largest observational cohort study in patients with low to intermediate likelihood undergoing coronary CTA in the ED. More importantly, at this point it may be impossible to repeat a study in which caregivers remain blinded to the results of coronary CTA, given the proven high negative predictive value of coronary CTA and the fact that randomized trials are already underway. Also, optimally our probability revision would have included a clinical risk stratification algorithm such as the TIMI score, to demonstrate the incremental value. However, 95% of patients in this population were at low TIMI risk score and stratification was not possible. This may emphasize the limitations of the TIMI score in the large population of low risk patients. This is a single center trial and the population, due to IRB recommendations (i.e. conservative creatinine threshold <1.3 mmol/ml) may have resulted in a slightly healthier population than the chest pain population in that CT would be used in clinical practice. However, the observed event rate of 8% is consistent with a low to intermediate risk of ACS.27