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The Role of Coronary CT Angiography in Acute Coronary Syndromes

Azeem S Sheikh1, Nadeem S Sheikh2, Samira Yahya3

1 Consultant Interventional Cardiologist, Sandwell & West Birmingham Hospitals NHS Trust, Birmingham, UK;
2 Former Chairman and Dean Department of Pathology, Bolan University of Medical and Health Sciences, Quetta, Balochistan, Pakistan;
3 Former Senior Education Fellow, East Lancashire Hospitals NHS Trust, Blackburn, UK.

Conflict-of-interest statement: The author(s) declare(s) that there is no conflict of interest regarding the publication of this paper.

Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http: //creativecommons.org/licenses/by-nc/4.0/

Correspondence to: Azeem S Sheikh, Consultant Interventional Cardiologist, Sandwell & West Birmingham Hospitals NHS Trust, Dudley Road, Birmingham, B18 7QH, United Kingdom.
Email: drazeemsheikh@hotmail.com
Telephone: +44 121 507 4282

Received: November 16, 2021
Revised: December 1, 2021
Accepted: December 6 2021
Published online: December 15, 2021

ABSTRACT

Coronary CT angiography has become an important tool in evaluating patients presenting to the emergency department with acute chest pain. In patients with intermediate or low-risk of acute coronary syndrome, the current consensus recommends Coronary CT angiography for assessment of coronary artery disease. An understanding of the CT features of ACS can facilitate in making a prompt and precise diagnosis which would lead to better clinical outcomes in this cohort. We review the current evidence and the features of high-risk plaque on coronary CT angiography in this article.

Key words: Coronary CT angiography; CCTA; Acute coronary syndrome; Acute chest pain; Vulnerable plaques; High-risk plaques

© 2021 The Authors. Published by ACT Publishing Group Ltd. All rights reserved.

Sheikh AS, Sheikh NS, Yahya S. The Role of Coronary CT Angiography in Acute Coronary Syndromes. Journal of Cardiology and Therapy 2021; 8(1): 981-986 Available from: URL: http://www.ghrnet.org/index.php/jct/article/view/3239

INTRODUCTION

Acute chest pain is one of the commonest presenting complaints in patients presenting to the emergency department (ED). It accounts for approximately 700 000 presentations to the ED per year in England and Wales and for 25% of emergency medical admissions[1]. A prompt diagnosis and exclusion of acute coronary syndrome is crucially important as missed diagnosis is linked to poor clinical outcomes.

Patients presenting with non-ST elevation acute coronary syndrome (NSTACS) are categorized into high-risk and intermediate or low-risk for their tendency to progress to myocardial infarction or death based on their presentation, evolving ECG changes, cardiac biomarkers and haemodynamic instability[2].

In high-risk acute coronary syndrome (ACS) cohort, an immediate coronary angiography with a view to intervene, if needed, should be performed as soon as possible, to try and salvage the viable myocardium. In patients with intermediate or low-risk of ACS, the current consensus recommends Coronary CT angiography for assessment of coronary artery disease[3,4]. Table 1 shows the current guidelines on the use of Coronary CT angiography in patients with non-ST elevation Acute Coronary Syndrome.

Table 1 Use of Coronary CT angiography in patients with non-ST elevation Acute Coronary Syndrome
GuidelineRecommendationEvidence
2020 ESC guidelines[3]CCTA is recommended as an alternative to invasive angiography to exclude ACS when there is a low-to-intermediate likelihood of CAD and when cardiac troponin and/or ECG are normal or inconclusiveClass I (Level of evidence A)
2014 AHA/ACC guidelines[4]In patients with possible ACS and a normal ECG, normal cardiac troponins, and no history of CAD, it is reasonable to initially perform coronary CT angiography to assess coronary artery anatomyClass IIa (Level of evidence A)

The role of coronary CT angiography (CTA) in patients presenting with ACS gained significant importance during the course of COVID-19 pandemic[5-7]. The diagnostic accuracy of 64 – slice coronary CTA has been scrutinized substantially in patients with stable coronary artery disease. Coronary CTA has distinctive sensitivity (>95%) and negative predictive value (>95%) with an outstanding specificity for the detection of coronary artery disease and helps in making a prompt diagnosis when compared with conventional functional testing[8].

The recent trials have demonstrated that coronary CTA is a safe and an efficient way of discharging low-risk chest pain patients from the emergency department[9-11]. The CT-STAT (Coronary Computed Tomographic Angiography for Systematic Triage of Acute Chest Pain Patients to Treatment) trial revealed a 54% reduction in time to diagnosis and a 38% reduction in costs of care between coronary CTA and myocardial perfusion imaging with no difference in major adverse cardiac events (MACE) at 60 days[9].

In the CT Angiography for Safe Discharge of Patients with Possible Acute Coronary Syndromes (ACRIN-PA) trial[10], 50% increase in discharge was demonstrated without any increase in MACE at 30 days in a cohort with a normal coronary CTA when it was compared to the standard of care.

The ROMICAT II (Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography II) trial evaluated a strategy incorporating coronary CTA with standard care in assessing patients presenting to the emergency department with acute chest pain. The trial demonstrated that the patients in coronary CTA group had significantly shorter length of stay (8 versus 26 hours) and higher rates of direct discharge from the emergency department, and no significant difference in the rate of major adverse cardiac events at 28 days[11]. Nonetheless, the cumulative costs at 28 days were noted to be higher in the coronary CTA group, as more patients in this cohort underwent further investigations after initial discharge.

The CATCH (Cardiac cT in the treatment of acute Chest pain) trial compared coronary CTA with standard care among 600 low-to-intermediate risk patients presenting to the emergency department with acute chest pain and the long-term clinical impact of coronary CT angiography-guided strategy was evaluated. The study demonstrated that the coronary CTA group had better clinical outcomes (composite of cardiac mortality, myocardial infarction, hospitalization for unstable angina, late-symptom-driven-revascularization, and readmission for chest pain) at a median follow-up of 18.7 months[12].

At present, Coronary CTA may be more appropriate to the patients in the low-risk NSTEACS. Without elevated cardiac biomarkers and in the absence of recurrent chest pain, it is recommended that this cohort should undergo a stress test to look for evidence of inducible ischaemia. Coronary CTA is recommended in this cohort only if the stress test demonstrated significant ischaemia. Coronary CTA may replace the stress test as the first investigation in this cohort, if the stress testing is inconclusive. Table 2 shows the Coronary CTA protocol. Table 3 shows the pre-medications for Coronary CTA. Table 4 shows the contra-indications to Coronary CTA.

Table 2 Coronary CT Angiography protocol.
Administration of β - blockers - if the heart rate > 65 BPM
Administration of nitroglycerine
Prospective ECG - gating (or retrospectively gated helical mode).
Calcium score reported in the form of Agatston score
Post-processing: axial image review, multi-planar reformation and maximum intensity projection.
Optional image review: curved multi-planar reformation and volume rendered reconstruction.

Table 3 Pre-medications for Coronary CT angiography
Check heart rate and blood pressure before administration of any medications
Administration of nitrates (400-800 µg of sublingual nitroglycerin e.g. 1-2 sprays)
Administration of ß-blocker (to target pulse of ≤ 65 bpm)
metoprolol 50-100 mg one hour before the exam
or metoprolol 5mg iv followed of monitoring for 5 min repeatedly up to 15-20 mg

Table 4 Contra-indications to Coronary CTA.
Absolute contraindicationsRelative contraindications
Severe or anaphylactic reaction to contrastInability to control heart rate
Haemodynamic instabilityPregnancy
Severe renal impairmentSevere aortic stenosis
Acute myocardial infarctionAsthma
Decompensated heart failureMorbid obesity
Contraindications to ß-blockers
2nd or 3rd-degree atrioventricular block
Systolic blood pressure ≤ 90 mmHg
Asthma
Contraindications to nitrates
Severe aortic stenosis
Systolic blood pressure ≤ 90 mmHg

ROLE OF CORONARY CTA IN PREDICTING OUTCOMES

The published evidence suggests that a normal coronary CTA is associated with low major adverse cardiac events in the following years[13]. The most notable characteristic of coronary CTA is in predicting magnificent outcomes in patients with normal results. The long-term data beyond 5 years demonstrates excellent prognosis for patients with normal coronary CTA with a negative likelihood ratio of 0.008 for MACE, with the risk for MACE increasingly exponentially as the plaque burden increases[14-17].

Coronary abnormalities on Coronary CT angiography

There is a strong evidence to suggest that acute myocardial infarction transpires not only from significantly stenotic lesions but from ‘vulnerable’ plaque irrespective of the degree of stenosis.

Plaques that are vulnerable to rupture are labelled as thin-cap fibro-atheroma which share identical histopathological features as ruptured plaques with the exception that the fibrous caps are nonetheless intact.

Thin-cap fibro-atheroma (TCFA) is widely recognised as a precursor for plaque rupture, which, in turn, is linked to the majority of cases of acute coronary syndrome. Histologically, TCFA is characterised as a large necrotic core with an overlying thin intact fibrous cap (< 65 μm), macrophage infiltration and usually increased number of intra-plaque vasa vasorum[18]. Figure 1 is a diagrammatic illustration of stable and unstable or vulnerable plaques. It has been shown that TCFA is a substantial predictor for expeditious development of angiographic stenosis (2) and a strong predictor of future cardiac events[19,20]. The term “vulnerable plaque” has therefore been used to describe rupture prone plaques prior to the occurrence of an event[20].

Figure 1 Features of stable and unstable/vulnerable plaque with thin-cap fibro-atheroma; gratefully acknowledged and reproduced from reference 29.

‘High-risk plaque’ on coronary CTA

The recent published work is more focussed on identifying plaque features that may determine it ‘high risk’ for rupture. Acute myocardial infarction is triggered by vulnerable plaque rupture ensuing in obstructive coronary artery stenosis or a complete occlusion. A culprit lesion is described as a 70% stenosis with non-calcified or a mixed calcified and non-calcified plaque accompanied by low attenuation plaque, positive remodelling, spotty calcification and the napkin-ring sign on coronary CTA. The high-risk plaque features on coronary CTA are shown in Table 5 and Figure 2(A - D).

When a patient present with acute coronary syndrome, two predominant variations occur within a precursor lesion vulnerable features[21]. The first of these is tearing of the thin cap with resultant expulsion of the lipid core of the plaque into the bloodstream. The second variation is the formation of a thrombus at the site of the ruptured plaque.

In patients with ACS, Chun et al[21] found no difference in the prevalence of features of low attenuation plaque and the napkin-ring sign among precursor and culprit lesions on coronary CTA. On the other hand, complete occlusion suggesting thrombus formation and myocardial hypo-attenuation seem to suggest that myocardial necrosis is more frequent in a culprit lesion as opposed to a precursor lesion on coronary CTA[21].

Table 5 High-risk plaque features on Coronary CTA.
FeatureDefinition
Positive remodellingOuter vessel diameter at the plaque ≥1.1 times that of adjacent uninvolved vessel
Low attenuation plaqueNon-calcified plaque measuring <30 HU, indicating a lipid core
Napkin-ring signPeripheral higher attenuation of the non-calcified portion of the plaque
Spotty calcium Small calcified plaque (density ≥ 130 HU separately visualised from the lumen, diameter <3 mm in any direction, but also length <1.5 times vessel diameter and width <2/3 times vessel diameter)

Figure 2 Illustrations showing high-risk plaque features on coronary CT angiography; gratefully acknowledged and reproduced from reference 29. A: Positive re-modelling: Positive remodelling of a non-calcified plaque in the mid right coronary artery. B: Low – attenuation plaque: Lesions associated with plaque rupture have a large lipid rich core, which appears as low attenuation. C: Napkin – ring sign: Central low attenuation area adjacent to the coronary lumen and a higher “ring–like” attenuation tissue surrounding this central area. D: Spotty calcification: Spotty calcifications are defined as calcifications <3 mm[25].

Coronary CTA features in Unstable Angina

The physiognomy of unstable angina on Coronary CTA mimics that of acute myocardial infarction; the only difference being the lack of wall motion abnormality and myocardial hypo-attenuation due to the absence of myocardial necrosis[22].

Meijboom et al[23] demonstrated that the sensitivity of detecting significant coronary stenoses on a patient-by-patient analysis was 100%, specificity 75%, and positive and negative predictive values were 96% and 100%, respectively. In segments where it was difficult to interpret due to heavy calcification, there was a tendency for observers to score these as positive for significant stenosis in order to reduce the chance of missing an important lesion. They suggested that this ‘‘defensive scoring’’ approach is also likely to be used in clinical practice when evaluating symptomatic patients. The high negative predictive value of the coronary CTA irrespective of significant coronary calcification and the high prevalence of coronary artery disease demonstrate that significant coronary disease can be ruled out with confidence in this cohort.

In view of the impressive negative predictive value[23], a negative coronary CTA would cater for patients to be discharged confidently. The cohort with non-obstructive coronary artery disease on coronary CTA would continue to be managed conservatively, in conjunction with secondary prevention, and necessitating any future tests based on the symptomology.

Vulnerable plaque and risk of future cardiac event

Not all vulnerable plaques on coronary CTA result in ACS. Motoyama et al[24] described that the manifestation of plaque progression on serial coronary CTA was linked to a heightened risk of cardiac event in future. The plaque progression is defined as an increasing size of lipid core or increasing amount of coronary stenosis of follow-up CT. This demonstrates that in order to predict a future cardiac event progression of vulnerable plaque morphology is pivotal than just a vulnerable plaque morphology seen on coronary CTA at a given time.

Motoyama et al[25] matched coronary CTA features of 38 patients with acute coronary syndrome with 33 patients who had stable angina. The coronary morphological characteristics showed that the plaques in ACS group had higher frequency of non-calcified plaques < 30 Hounsfield Units (HU) (79% vs. 9%, p < 0.0001), spotty calcification (63% vs. 21%, p = 0.0005) and positive remodelling (87% vs. 12%, p < 0.0001). The presence of all three features exhibited a high positive predictive value, and their absence demonstrated a high negative predictive value for future cardiac events.

Motoyama et al[26], in a large prospective study with a cohort of 1,059 patients, described that coronary CTA features of low-attenuation plaque and positive remodelling were linked with the subsequent occurrence of acute coronary events. ACS occurred in 10/45 (22%) who had these two features on coronary CTA compared with 4/820 (0.5%) who did not have these features. It was important to note that none of the 167 patients who had normal coronary CTA sustained acute cardiac events (p < 0.001).

Kashiwagi et al[27] suggested that presence of a ring-like attenuation on coronary CTA may be a surrogate marker of TCFAs after contemplating OCT and coronary CTA findings. They studied 105 patients with coronary artery disease and divided the cohort into TCFA and non-TCFA group according to the OCT findings. Coronary CTA-verified positive remodelling was detected more often in the TCFA (75%) than in the non-TCFA group (30%, p < 0.001). The TCFA group also exhibited LAP more frequently; CT attenuation value in the TCFA group (35 ± 32 HU) was significantly lower than the non-TCFA group (62 ± 34 HU, p < 0.001). Exceptionally a ring-like attenuation in the TCFA group was found to be 11-fold more frequent than in the non-TCFA group (44% vs. 4%, p < 0.001). The sensitivity, specificity, positive predictive value and negative predictive value of ring-like enhancement for detecting TCFA are 44%, 96%, 79%, and 85%, respectively[28].

Conclusions

Coronary CTA is a reliable diagnostic tool of excluding ACS in low-to-intermediate risk cohort in view of its high negative predictive value. An understanding of the CT features of ACS can facilitate in making a prompt and precise diagnosis which would lead to better clinical outcomes in this cohort.

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