Note to myself and my readers: This is an outstanding review article worth reviewing more than once (often).
Today, I review, link to, and excerpt from The Journal Of Cardiovascular Development And Disease’s “Coronary CT Angiography in the Emergency Department: State of the Art and Future Perspectives” [PubMed Abstract] [Full-Text HTML] [Full-Text PDF]. J Cardiovasc Dev Dis. 2025 Jan 27;12(2):48. doi: 10.3390/jcdd12020048.
All that follows is from the above resource.
Abstract
About 5% of annual access to emergency departments (EDs) and up to 25–30% of hospital admissions involve patients with symptoms suggestive of acute coronary syndrome (ACS). The process of evaluating and treating these patients is highly challenging for clinicians because failing to correctly identify an ACS can result in fatal or life-threatening consequences. However, about 50–60% of these patients who are admitted to the hospital because of chest pain are found to have no ACS. Coronary computed tomographic angiography (CCTA) has emerged as a proposed new frontline test for managing acute chest pain in the ED, particularly for patients with low-to-intermediate risk. This narrative review explores the potential of adopting an early CCTA-based approach in the ED, its significance in the era of high-sensitivity troponins, its application to high-risk patients and its prognostic value concerning atherosclerotic burden and high-risk plaque features. Additionally, we address clinical and technical issues related to CCTA use for triaging acute chest pain in the ED, as well as the role of functional testing. Finally, we aim to provide insight into future perspectives for the clinical application of CCTA in the ED.
Keywords: coronary computed tomographic angiography, emergency department, acute chest pain, acute coronary syndrome, coronary artery disease 1. Introduction
About 5% of annual access to the emergency department (ED) and up to 25–30% of hospital admissions involve patients with symptoms suggestive of acute coronary syndrome (ACS) [1]. The process of evaluating and treating these patients is highly challenging for clinicians because failing to correctly identify an ACS can result in fatal or life-threatening consequences [2]. However, about 50–60% of patients presenting with acute chest pain are found to have no ACS [3,4]. This over-triage carries considerable economic consequences, with related costs of around USD 14 billion for the United States healthcare system [5]. Furthermore, this overcrowding in the ED has been associated with worse clinical outcomes for acute chest pain patients, making rapid triage essential for both health and economic reasons [6,7]. From this perspective, coronary computed tomography angiography (CCTA) has been proposed to enhance decision-making in the ED for patients with no known previous coronary artery disease (CAD). Considering the high accuracy of CCTA in ruling out CAD, it allows a rapid evaluation of the degree of coronary atherosclerosis, drastically reducing the time-to-discharge of patients without significant CAD and ensuring more appropriate referral for invasive coronary angiography (ICA) and myocardial revascularization [8,9,10,11].
In this review, we explore the potential of an early CCTA-based strategy for patients with chest pain in the ED setting, its significance in the era of high-sensitivity troponins and its application for high-risk patients. Additionally, we discuss the prognostic value of the atherosclerotic burden, the high-risk plaque features and the role of functional testing in the acute setting.
2. Coronary CT Angiography-Based Approach in the Emergency Department
Extensive recent evidence and current guidelines support CCTA as a first-line imaging strategy for the rapid triage of low-to-intermediate risk patients presenting with acute chest pain to the ED (Table 1). The main advantages of an anatomical CCTA-based approach in the ED setting include its ability to (1) quickly rule out significant CAD in low-to-intermediate-risk patients thanks to its high sensitivity and negative predictive value; (2) shorten the time-to-diagnosis; (3) decrease the ED length-of-stay; (4) reduce the overall cost of care.
Firstly, data from the ROMICAT trial showed that, among patients presenting to the ED with acute chest pain and in whom the initial assessment was inconclusive, CCTA accurately excluded ACS in 71% of cases, demonstrating the absence of significant CAD (with a negative predictive value of 100%) [9]. Other studies suggest that a CCTA-based strategy for low-to-intermediate-risk patients presenting with suspected ACS allows for the safe and rapid discharge of about 50% of these patients, who would otherwise be admitted [8,9,10,11].
Secondly, both in the ROMICAT II trial and in the CT-STAT trial, the CCTA implementation in patients presenting with typical chest pain led to a 44% and 55% reduction in time-to-diagnosis, respectively, compared with rest/stress myocardial perfusion imaging (MPI) [12,13].
Thirdly, the ROMICAT II trial demonstrated that using CCTA significantly reduced ED length-of-stay by approximately 7 h and led to a higher rate of direct discharge from the ED, enhancing efficiency without compromising patient outcomes [13]. Similarly, in the CT-COMPARE trial, the implementation of CCTA was associated with a reduction in ED length-of-stay by approximately 6 h [14]. In all these studies, CCTA was used as a complement to clinical assessments, including troponins and risk scores. These parameters were crucial for stratifying patient risk and interpreting CCTA findings. Combining CCTA with traditional markers, rather than using CCTA alone, may enhance early triage and discharge decisions, providing a comprehensive patient evaluation and improving diagnostic accuracy. Furthermore, it is important to note that the study population primarily consisted of individuals with a low-to-intermediate risk profile and with a mean age under 60 years, which may influence the accuracy metrics. Across these studies, the sensitivity and specificity data are influenced by the prevalence of CAD, patient age and associated calcification levels. Older populations, with a higher burden of calcification, are more likely to experience higher false-positive rates. This context should be considered when interpreting the diagnostic accuracy metrics reported for CCTA in these trials and applying the result to older populations.
Lastly, in the CT-COMPARE trial, a CCTA-based strategy in patients presenting to the ED with acute chest pain led to a 20% reduction in hospital costs compared with the ECG exercise stress test [14]. This cost reduction encompassed all inpatient and outpatient costs associated with the index admission, including labor, diagnostics, pathology, pharmaceuticals, bed days and consumables, while excluding societal and opportunity costs. These findings were confirmed by the CT-STAT trial which demonstrated a 38% reduction in overall healthcare costs for patients assigned to the CCTA group compared to those in the MPI group [12]. Economic evaluations of CCTA often rely on key assumptions regarding the cost of the procedure, including reimbursement rates, operational efficiency and resource allocation within healthcare systems. These analyses also account for downstream cost savings from avoiding unnecessary hospital admissions, invasive procedures or additional testing. However, variations in local pricing, scanner availability and staffing requirements can significantly influence the economic outcomes.
Furthermore, CCTA offers several advantages compared to other diagnostic techniques available for managing patients with suspected ACS. In particular, it can detect the presence of other causes of chest pain (i.e., coronary artery abnormalities, aortic dissection and extra-cardiac causes), thus allowing clinicians to promptly initiate appropriate treatments [15,16].
2.1. Coronary CT Angiography in the Era of High-Sensitivity Troponins
Over the years, conventional cardiac troponin (cTn) tests have been largely replaced by high-sensitivity cardiac troponin (hs-cTn) assays in most centers. These hs-cTn assays have a higher negative predictive value (NPV), so normal levels can effectively exclude the presence of an ACS in ED patients presenting with acute chest pain [17,18]. However, the trade-off of this increased sensitivity is reduced specificity, meaning that hs-cTn assays can yield positive results not only in cases of myocardial infarction but also in various critical conditions associated with myocardial injury [19,20]. In these cases, the addition of CCTA beyond high-sensitivity troponin assays may be necessary to determine the underlying cause of chest pain and guide appropriate management.
In a study conducted in 500 patients, the use of CCTA was associated with less outpatient testing and lower direct medical costs compared to standard optimal care encompassing hs-cTn assays [21]. However, the BEACON study showed that CCTA did not improve the identification of patients, with significant CAD requiring coronary revascularization, nor did it reduce hospital stay or increase the rate of direct discharge from the ED [21].
Other studies provided promising evidence for the potential benefits of integrating CCTA into the ED setting, particularly for patients with intermediate levels of hs-cTn or without a significant “rise and fall” pattern [22,23].
The PRECISE-CTCA study showed that in patients presenting to the ED because of acute chest pain, in whom intermediate hs-cTn concentrations were found (between 5 ng/L and the sex-specific 99th percentile), there is a higher probability of CAD compared to those with low hs-cTn concentrations (<5 ng/L). In this specific subgroup of patients, CCTA may help identify those with occult CAD or with high-risk plaques, thereby improving clinical outcomes [24].
In a study by Ferencik et al., early advanced CCTA assessment (involving not only the degree of stenosis but also the plaque features) combined with hs-cTn evaluation may improve risk stratification and diagnostic accuracy in patients with suspected ACS and intermediate hs-cTn levels [25]. In these patients, the absence of coronary stenosis ≥ 50% and high-risk plaque ruled out ACS (ACS rate 0%), whereas patients with both stenosis ≥ 50% and high-risk plaque were at high risk for ACS (ACS rate 69.2%).
Finally, the COURSE trial is an ongoing study that aims to determine whether an early CCTA may be more efficient than standard care in patients with inconclusive high-sensitivity troponin results. Preliminary goals include reducing unnecessary hospital admissions and ICA [26].
2.2. Coronary CT Angiography for the Subgroup of High-Risk Patients
Although CCTA finds its greatest application in ED patients at low-to-intermediate risk, it might also be useful in high-risk patients presenting with acute chest pain.
Several studies have investigated the role of CCTA in patients presenting to the ED with a clinical picture of non-ST-segment elevation acute myocardial infarction (NSTEMI), demonstrating that CCTA may significantly reduce the need for ICA in a large number of cases [22,27]. It is especially advantageous for patients at greater risk of complications from invasive procedures, such as older individuals or those with a high risk of bleeding [27].
In the VERDICT trial, CCTA maintains high accuracy to rule out clinically significant CAD (defined as stenosis ≥ 50%) in patients with documented NSTEMI with a per-patient NPV of 91% [28]. Furthermore, it was observed that approximately one-third of patients with NSTEMI had no clinically significant CAD, indicating the potential role of coronary CTA to safely defer ICA in nearly one-third of these high-risk cases, with no increase in major adverse cardiovascular events (MACE) after a median follow-up of 4 years [28].
Other studies confirmed these results, showing that an early CCTA may reduce the need for ICA in NSTEMI patients by approximately 30 to 40%, compared with routine clinical care [29].
2.3. The Prognostic Value of Atherosclerosis Burden and High-Risk Plaques
Over the last few years, CCTA has gained additional prognostic value beyond merely assessing the severity of coronary stenosis. Indeed, CCTA performed in the ED setting also enables the evaluation of atherosclerotic burden and the presence of high-risk plaque features, both of which are associated with unfavorable outcomes (Figure 1).
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What follows between these lines are definitions and links to the “High-risk plaques and functional assessment” in the chart above.
FFR-CT: Google AI Overview
CT-FFR (Computed Tomography-derived Fractional Flow Reserve) is a powerful, non-invasive imaging technique that uses a standard coronary CT scan and advanced computational fluid dynamics to create a 3D model of your heart arteries, revealing the functional impact of blockages (stenosis) on blood flow, helping doctors accurately diagnose Coronary Artery Disease (CAD) and decide if invasive procedures like angiography or stents are truly needed, often avoiding unnecessary interventions. It works by analyzing blood flow physics within the arteries from the CT data, assigning color-coded values (red for severe, blue for normal) to show blockage severity, and guiding treatment decisions with high accuracy, especially for intermediate lesions.
Coronary CT Perfusion: Google AI Overview
Coronary CT Perfusion (CTP) is an advanced cardiac imaging technique using rapid CT scans and contrast dye to assess blood flow (perfusion) to the heart muscle (myocardium) at rest and during stress, helping diagnose ischemic heart disease by identifying areas with poor blood supply, combining functional (perfusion) and anatomical (CT Angiography) information for better accuracy than CTA alone, especially in complex cases, with evolving software improving artifact reduction and quantitative analysis.
Cardiac Perivascular Fat Inflammation Index: Google AI Overview
The Cardiac Perivascular Fat Inflammation Index (FAI) is a powerful imaging biomarker from CT scans that measures inflammation in the fat surrounding coronary arteries, revealing vulnerable plaques and predicting cardiac events, helping to refine cardiovascular risk assessments beyond traditional methods like calcium scores, though automated tools are needed for widespread clinical use. It works by detecting changes (increased attenuation) in the perivascular adipose tissue (PVAT) that signal underlying inflammation, offering early insight into coronary artery disease (CAD) progression and potential plaque instability.
Coronary Positive Remodeling: Google AI Overview
Positive remodeling (PR) in a coronary artery is when the artery outwardly expands to compensate for growing plaque, keeping the inner channel (lumen) open, but creating a “silent”, vulnerable lesion that can rupture and cause a heart attack without prior symptoms. It’s a high-risk feature where the artery wall grows bigger to maintain flow, making it hard to detect on standard tests, but modern imaging like CT scans (CCTA) can identify it, signaling a greater risk for future cardiac events.
Napkin Ring Sign, Coronary CTA: Google AI Overview
The “napkin-ring sign” on a coronary computed tomography angiography (CTA) is a specific imaging feature of a high-risk, vulnerable atherosclerotic plaque that is strongly associated with an increased risk of future acute coronary syndrome (ACS) events, such as a heart attack.
Low Attenuation On Coronary CT Angiogram: Google AI Overview
Low attenuation on a Coronary CT Angiogram (CCTA) signifies a type of “soft” plaque, rich in lipids, making it a crucial marker for vulnerable plaques that are prone to rupture, causing heart attacks (myocardial infarction), even more so than just the degree of artery narrowing (stenosis). This plaque appears dark (low Hounsfield Units, <30 HU) and indicates a high-risk lesion with a large necrotic core, a strong predictor of future cardiovascular events, especially in stable chest pain patients.
Spotty Calcification On Coronary CT Angiogram: Google AI Overview
Spotty calcification on a Coronary CT Angiogram (CCTA) signifies vulnerable, high-risk plaque, often linked to inflammation and a greater chance of plaque rupture and acute events like heart attacks, unlike heavier calcification which indicates stable plaque burden. These small, dense calcium deposits (<3mm) within softer, low-attenuation plaque suggest early, active disease, requiring careful assessment for plaque instability, positive remodeling, and other risk factors, even if the artery isn’t severely narrowed yet.
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The most compelling evidence linking atherosclerotic burden to unfavorable outcomes derives from the CONFIRM registry [30,31]. In another study by Bittencourt et al., the burden of coronary atherosclerosis, as documented by CCTA, has proven to be an independent prognostic factor in addition to the degree of stenosis: the segment involvement score (SIS) well correlates with survival (irrespective of stenosis severity), so an extensive plaque burden (SIS > 4) with non-obstructive plaque has the same risk for MACE as a lower plaque burden (SIS < 4) with obstructive plaque [32].
CCTA performed in the ED setting may be helpful to also identify high-risk plaque features, i.e., positive remodeling (>10% increase in vessel outer diameter), low attenuation plaque (plaque measuring < 30 HU), napkin-ring sign (plaque with a central area of low CT attenuation and peripheral ring of high CT attenuation) and spotty calcification (calcification ≤ 3 mm in any direction) [33].
Other features, such as increased plaque volume and fibro-fatty necrotic core, have been also associated with incident ACS: in the ICONIC trial both high-risk plaque features and quantitative assessment of fibrofatty necrotic core plaque volume were associated with incident ACS [34].
The perivascular fat inflammation index (FAI) has also been proposed as a potential marker for identifying high-risk plaque. The CRISP-CT study shows that higher pericoronary FAI values, indicating a higher inflammatory burden, are associated with a higher risk of adverse cardiac events [35]. Indeed, data from ROMICAT II showed that patients with high-risk plaque features on CCTA had an increased risk of ACS, independently of stenosis severity and clinical risk assessment [36].
Similar characteristics have been shown to indicate vulnerable plaque in histological studies (e.g., necrotic lipid-rich core, thin cap fibroatheroma, positive remodeling, spotty calcium) [37,38].
Although CCTA may help identify high-risk plaque with additional prognostic value, how plaque morphology influences decision-making in the ED setting remains unclear [39]. Further studies are needed to determine the optimal management strategies based on CCTA findings, particularly in patients presenting with acute chest pain.
2.4. Beyond the Anatomy: Functional Testing with Coronary CT Angiography
In recent years, CCTA has evolved, not only providing anatomical information about the degree of stenosis and high-risk plaque features but also offering functional insights about the physiology of lesion-specific ischemia and the hemodynamic impact of coronary stenosis using CT-derived fractional flow reserve (FFR-CT) and stress myocardial CT perfusion (CTP). This becomes particularly relevant in cases of intermediate coronary stenosis, where the presence or absence of myocardial ischemia may significantly influence the choice of therapeutic strategy [40,41].
FFR-CT has revolutionized the field of non-invasive cardiac imaging. Integrating data from CCTA with computational fluid dynamics algorithms, it estimates the functional significance of coronary artery lesions. This makes FFR-CT highly comparable to ICA in terms of both sensitivity and specificity [42]. In the ED setting, FFR-CT can provide valuable clinical insights in patients with suspected ACS. In a post hoc analysis of the ROMICAT II trial, in more than 50% of cases, stenoses assessed to be anatomically severe on CCTA were downgraded using the FFR-CT algorithm. Conversely, up to one-third of patients with mild stenosis (25–50%) were found to have hemodynamically significant flow limitation (FFR-CT < 0.80) [43].
Stress myocardial CTP is based on the distribution of iodinated contrast material during its first pass through the myocardium. It is possible to identify myocardial perfusion defects as hypo-attenuating areas since the amount of contrast material is reduced [44]. In patients presenting to the ED with acute chest pain, a combined stress CTP/CCTA strategy can result in fewer referrals for ICA compared to CCTA alone [45] and significantly reduced hospital costs and length-of-stay when compared to SPECT myocardial perfusion [46].
2.5. Patient Selection and Clinical Issues
Before performing CCTA in patients presenting to the ED with acute chest pain, it is crucial to stratify patients into different risk categories for ACS. There are different scores, such as the HEART pathway, EDACS score and ADAPT score, which can help to optimize the use of CCTA and ensure appropriate patient management [19,47].
The HEART pathway incorporates five key components: history, ECG, age, risk factors and troponin assessment. Patients are categorized into three risk levels: low risk (score < 3), intermediate risk (score 4–6) and high risk (score 7–10), based on the cumulative result of each item [48]. The EDACS score includes patient age, sex, cardiovascular risk factors and troponin serum levels [49]. The ADAPT score also incorporates the TIMI score, troponin measurement and ECG findings [50].
Numerous studies have suggested that CCTA in the ED setting is most effective in patients with chest pain and a low-to-intermediate risk for ACS [9,10,11,12], especially those with intermediate values of hs-cTn concentration (below the sex-specific 99th percentile), non-ischemic ECG changes or mildly abnormal functional testing [21,22,23,24]. In these groups, only a small percentage of patients have obstructive CAD, while most have normal or non-obstructive coronary arteries. Consequently, CCTA can be used effectively to rule out ACS and support the safe discharge of these patients.
However, CCTA may also be considered in patients with a high pre-test probability of CAD but without definite evidence of ACS by ECG and troponins, to confidently exclude CAD [25,26,27], especially in specific scenarios, such as patients at high bleeding risk or with vascular access issues. In patients with known CAD and prior PCI or prior CABG with normal ECG and normal hs-cTn, CCTA may be considered if certain criteria are met (e.g., stent in a proximal coronary segment and >3 mm in diameter) [47].
Based on the results of recent research, the 2023 ESC Guidelines for the management of ACS support the use of CCTA in ED patients with acute chest pain and non-elevated (or uncertain) hs-cTn levels, no ischemic ECG changes and no recurrence of symptoms (Table 1) [51].
2.6. Technical Issues
The integration of CCTA into the ED workflow requires careful consideration of several key aspects to ensure its safe and effective implementation. This includes a clear definition of indications, contraindications, patient preparation and optimization of the CT image acquisition [47,52].
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