Coronary CT angiography for improved assessment of patients with acute chest pain and low-range positive high-sensitivity troponins: study protocol for a prospective, observational, multicentre study (COURSE trial).

INTRODUCTION: Current evaluation of patients suspected of a non-ST-elevation acute coronary syndrome (NSTE-ACS) involves the use of algorithms that incorporate clinical information, electrocardiogram (ECG) and high-sensitivity cardiac troponins (hs-troponins). While primarily designed to rule out NSTE-ACS safely, these algorithms can also be used for rule in of NSTE-ACS in some patients. Still, in a substantial number of patients, these algorithms do not provide a conclusive work-up. These patients often present with an atypical clinical profile and low-range positive hs-troponin values without a characteristic rise or fall pattern. They represent a heterogeneous group of patients with various underlying conditions; only a fraction (30%-40%) will eventually be diagnosed with a myocardial infarction. Uncertainty exists about the optimal diagnostic strategy and their management depends on the clinical perspective of the treating physician ranging from direct discharge to admission for invasive coronary angiography. Coronary CT angiography (CCTA) is a non-invasive test that has been shown to be safe, fast and reliable in the evaluation of coronary artery disease. In this study, we will determine the usefulness of CCTA in patients with acute chest pain and low-range positive hs-troponin values. METHODS AND ANALYSIS: A prospective, double-blind, observational, multicentre study conducted in the Netherlands. Patients aged 30-80 years presenting to the emergency department with acute chest pain and a suspicion of NSTE-ACS, a normal or non-diagnostic ECG and low-range positive hs-troponins will be scheduled to undergo CCTA. The primary outcome is the diagnostic accuracy of CCTA for the diagnosis of NSTE-ACS at discharge, in terms of sensitivity and negative predictive value. ETHICS AND DISSEMINATION: This study was approved by the Medical Research Ethics Committee of Erasmus Medical Center in Rotterdam, the Netherlands (registration number MEC-2017-506). Written informed consent to participate will be obtained from all participants. This study's findings will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT03129659).

Prognostic implications of non-culprit plaques in acute coronary syndrome: non-invasive assessment with coronary CT angiography.

AIMS: Non-culprit plaques are responsible for a substantial number of future events in patients with acute coronary syndrome (ACS). In this study, we evaluated the prognostic implications of non-culprit plaques seen on coronary computed tomography angiography (CTA) in patients with ACS. METHODS AND RESULTS: Coronary CTA was performed in 169 patients (mean 59 ± 11 years, 129 males) admitted with ACS. Data sets were assessed for the presence of obstructive non-culprit plaques (>50% luminal narrowing), segment involvement score, and quantitative measures of plaque burden, after censoring initial culprit plaques. Follow-up was performed for the occurrence of major adverse cardiovascular events (MACEs) unrelated to the initial culprit plaque; cardiac death, second ACS, or coronary revascularization after 90 days. After a median follow-up of 4.8 (IQR 2.6-6.6) years, MACE occurred in 36 (24%) patients: 6 cardiac deaths, 16 second ACS, and 14 coronary revascularizations. Dyslipidaemia (hazard ratio [HR] 3.1 [95% confidence interval 1.5-6.6]) and diabetes mellitus (HR 4.8 [2.3-10.3]) were univariable clinical predictors of MACE. Patients with remaining obstructive non-culprit plaques (HR 3.66 [1.52-8.80]) and higher plaque burden index (HR 1.22 [1.01-1.48]) had a more risk of MACE. In multivariate analysis, with diabetes, dyslipidaemia, and plaque burden index, obstructive non-culprit plaques (HR 3.76 [1.28-11.09]) remained an independent predictor of MACE. CONCLUSION: Almost a quarter of the study population experienced a new event arising from a non-culprit plaque during a follow-up of almost 5 years. ACS patients with remaining obstructive non-culprit plaques or high plaque burden have an increased risk of future MACE.

Restriction of the referral of patients with stable angina for CT coronary angiography by clinical evaluation and calcium score: impact on clinical decision making.

OBJECTIVE: To investigate the value of the calcium score (CaSc) plus clinical evaluation to restrict referral for CT coronary angiography (CTCA) by reducing the number of patients with an intermediate probability of coronary artery disease (CAD). METHODS: We retrospectively included 1,975 symptomatic stable patients who underwent clinical evaluation and CaSc calculation and CTCA or invasive coronary coronary angiography (ICA). The outcome was obstructive CAD (≥50 % diameter narrowing) assessed by ICA or CTCA in the absence of ICA. We investigated two models: (1) clinical evaluation consisting of chest pain typicality, gender, age, risk factors and ECG and (2) clinical evaluation with CaSc. Discrimination of the two models was compared. The stepwise reclassification of patients with an intermediate probability of CAD (10-90 %) after clinical evaluation followed by clinical evaluation with CaSc was assessed by clinical net reclassification improvement (NRI). RESULTS: Discrimination of CAD was significantly improved by adding CaSc to the clinical evaluation (AUC: 0.80 vs. 0.89, P < 0.001). CaSc and CTCA could be avoided in 9 % using model 1 and an additional 29 % of CTCAs could be avoided using model 2. Clinical NRI was 57 %. CONCLUSION: CaSc plus clinical evaluation may be useful in restricting further referral for CTCA by 38 % in symptomatic stable patients with suspected CAD. KEY POINTS: • CT calcium scores (CaSc) could proiritise referrals for CT coronary angiography (CTCA) • CaSc provides an incremental discriminatory value of CAD compared with clinical evaluation • Risk stratification is better when clinical evaluation is combined with CaSc • Appropriate use of clinical evaluation and CaSc helps avoid unnecessary CTCA referrals.

Coronary computed tomography versus exercise testing in patients with stable chest pain: comparative effectiveness and costs.

BACKGROUND: To determine the comparative effectiveness and costs of a CT-strategy and a stress-electrocardiography-based strategy (standard-of-care; SOC-strategy) for diagnosing coronary artery disease (CAD). METHODS: A decision analysis was performed based on a well-documented prospective cohort of 471 outpatients with stable chest pain with follow-up combined with best-available evidence from the literature. Outcomes were correct classification of patients as CAD- (no obstructive CAD), CAD+ (obstructive CAD without revascularization) and indication for Revascularization (using a combination reference standard), diagnostic costs, lifetime health care costs, and quality-adjusted life years (QALY). Parameter uncertainty was analyzed using probabilistic sensitivity analysis. RESULTS: For men (and women), diagnostic cost savings were €245 (€252) for the CT-strategy as compared to the SOC-strategy. The CT-strategy classified 82% (88%) of simulated men (women) in the appropriate disease category, whereas 83% (85%) were correctly classified by the SOC-strategy. The long-term cost-effectiveness analysis showed that the SOC-strategy was dominated by the CT-strategy, which was less expensive (-€229 in men, -€444 in women) and more effective (+0.002 QALY in men, +0.005 in women). The CT-strategy was cost-saving (-€231) but also less effective compared to SOC (-0.003 QALY) in men with a pre-test probability of ≥ 70%. The CT-strategy was cost-effective in 100% of simulations, except for men with a pre-test probability ≥ 70% in which case it was 59%. CONCLUSIONS: The results suggest that a CT-based strategy is less expensive and equally effective compared to SOC in all women and in men with a pre-test probability <70%.