Troponin-Guided Coronary Computed Tomographic Angiography After Exclusion of Myocardial Infarction

Background Patients with suspected acute coronary syndrome in whom myocardial infarction has been excluded are at risk of future adverse cardiac events. Objectives This study evaluated the usefulness of high-sensitivity cardiac troponin I (hs-cTnI) to select patients for further investigation after myocardial infarction has been excluded. Methods This is a prospective cohort study of patients presenting to the emergency department with suspected acute coronary syndrome and hs-cTnI concentrations below the sex-specific 99th percentile. Patients were recruited in a 2:1 fashion, stratified by peak hs-cTnI concentration above and below the risk stratification threshold of 5 ng/L. All patients underwent coronary computed tomography angiography (CCTA) after hospital discharge. Results Overall, 250 patients were recruited (61.4 ± 12.2 years 31% women) in whom 62.4% (156 of 250 patients) had coronary artery disease (CAD). Patients with intermediate hs-cTnI concentrations (between 5 ng/L and the sex-specific 99th percentile) were more likely to have CAD than those with hs-cTnI concentrations <5 ng/L (71.9% [120 of 167 patients] vs 43.4% [36 of 83 patients]; odds ratio: 3.33; 95% CI: 1.92-5.78). Conversely, there was no association between anginal symptoms and CAD (63.2% [67 of 106 patients] vs 61.8% [89 of 144 patients]; odds ratio: 0.92; 95% CI: 0.48-1.76). Most patients with CAD did not have a previous diagnosis (53.2%; 83 of 156 patients) and were not on antiplatelet and statin therapies (63.5%; 99 of 156 patients) before they underwent CCTA. Conclusions In patients who had myocardial infarction excluded, CAD was 3× more likely in those with intermediate hs-cTnI concentrations compared with low hs-cTnI concentrations. In such patients, CCTA could help to identify those with occult CAD and to target preventative treatments, thereby improving clinical outcomes.

after acute myocardial infarction has been ruled out, a significant proportion of patients may still have underlying CAD and are at risk of future adverse cardiac events. The optimal approach to select such patients for further investigation remains uncertain.
It is now increasingly recognized that high-sensitivity cardiac troponin (hs-cTn) concentrations within the normal reference range can aid in the triage of patients with suspected acute coronary syndrome. We previously identified and validated a rule-out threshold of 5 ng/L that maximizes the number of patients with suspected acute coronary syndrome who are identified as low risk at presentation with a negative predictive value of >99.5% for myocardial infarction or cardiac death at 30 days (4,5). This threshold has been incorporated into early rule-out pathways to expediate the evaluation of patients with suspected acute coronary syndrome (6). In contrast, those with intermediate troponin concentrations between 5 ng/L to 99th percentile diagnostic threshold are often triaged to further clinical observation and have substantially higher medium-and long-term risk of adverse cardiac events (4,5). We currently have limited understanding of the pathophysiological mechanisms for this observed increase in risk in those with intermediate troponin concentrations, and it is unclear whether this reflects unrecognized CAD. Insights here may help us develop evidence-based strategies to identify patients who are more likely to benefit from additional testing (7).
In patients with suspected acute coronary syndrome in whom myocardial infarction has been ruled out, we aim to determine whether those with intermediate troponin concentrations have a higher prevalence of CAD and whether troponin could be used to guide the selection of patients for coronary computed tomography angiography (CCTA).

METHODS STUDY DESIGN AND POPULATION. PRECISE-CTCA (Troponin to Risk Stratify Patients with Acute Chest
Pain for Computed Tomography Coronary Angiography) was a prospective cohort study (NCT04549805).
Between December 4, 2018 and October 6, 2020, we prospectively enrolled 250 patients older than 30 years of age who presented to the emergency department at the Royal Infirmary of Edinburgh, United Kingdom, with suspected acute coronary syndrome in whom acute myocardial infarction had been ruled out and peak hs-cTn concentrations were within the normal reference range. Patients were recruited in a 2:1 fashion stratified by peak hs-cTnI (ARCHITECT STAT troponin I assay; Abbott Laboratories) concentration above and below the risk stratification threshold of 5 ng/L (4,5).
Exclusion criteria were an inability to undergo CCTA due to severe renal failure (estimated glomer-  were subsequently classified according to the most significant stenosis identified on the CCTA, regardless of whether the vessel has been stented. Coronary stenoses that were bypassed by a vascular graft were not considered in the classification. Atherosclerotic plaque burden was quantified using the segment involvement, segment stenosis, and computed tomography (CT)Àadapted Leaman scores. The segment involvement score was calculated as the total number of segments with any plaque and ranged from 0 to 16 (12). The segment stenosis score also incorporated the severity of stenosis and ranged from 0 to 48. The CT-Leaman score incorporates weighting factors for the location of the plaque, the type of plaque (noncalcified, calcified, or mixed plaques) and the degree of stenosis, and ranges from 0 to 34.5 (13   Values are n (%), mean AE SD, or median (interquartile range).
Abbreviations as in Table 1.    There is now increasing evidence to support the use of CCTA over functional ischemia testing in patients with stable chest pain (32,33). Recent trials demonstrated that CCTA clarified the diagnosis of CAD and led to major improvements in patient outcomes by increasing the use of evidence-based preventative therapies (34). Furthermore, CCTA was cost-effective and led to less use of further downstream testing compared with functional testing (35,36). Secondary analyses of multiple randomized controlled trial data also showed that anatomical information provided by CCTA was an excellent predictor of prognosis (37)(38)(39)(40). In contrast, the extent of ischemia on functional testing was a poor discriminator of future risk (41). These data suggest that CCTA is likely to provide better diagnostic and prognostic information than that of functional testing to guide patient care once myocardial infarction has been ruled out.