High‐sensitivity cardiac troponin T as a predictor of acute Total occlusion in patients with non‐ST‐segment elevation acute coronary syndrome

Background A large percentage of patients with non‐ST‐segment acute coronary syndrome (NSTE‐ACS) present with acute total occlusion (TO) of some major epicardial vessel that does not generate electrocardiographic changes. Ongoing research into the methods of accurately predicting acute TO have not yielded great success. Hypothesis High‐sensitivity cardiac troponin T (hs‐cTnT) has a good predictive value for the presence of acute TO of the culprit artery in patients with NSTE‐ACS. Methods A single‐center retrospective study of 1011 patients diagnosed with NSTE‐ACS who underwent coronary angiography and hs‐cTnT measured on admission. The predictive value of hs‐cTnT in the presence of acute TO was assessed by the area under the ROC curve. Results The mean age of the population was 67.12 ± 13.18 and 74.1% were male. 7.3% of the patients presented with acute TO. The AUC for hs‐cTnT to predict acute TO was 0.95. A hs‐cTnT value of 1006 ng/L (71.8 fold of the URL) best predicted the presence of acute TO, with a sensitivity of 86% and specificity of 95% positive predictive value (PPV): 86% and negative predictive value (NPV): 94%. Conclusions Hs‐cTnT was a good predictor of acute TO in patients with NSTE‐ACS. Hs‐cTnT values greater than 1006 ng/L were highly predictive of acute TO of a major coronary vessel.

Despite advances in medical and interventional treatments, the morbidity and mortality of NSTEMI patients remains high. 5 Early invasive strategy with PCI has shown better clinical and angiographic outcomes in high risk patients with NSTEMI than conservative management or late PCI. 6 In this respect, there is a large percentage of patients with total occlusion (TO) of the culprit artery, diagnosed angiographically, presenting with NSTEMI. 7,8 Recent findings suggest that NSTEMI patients with TO of the culprit artery are at an increased risk of all-cause mortality and major adverse cardiac events. 9,10 It is difficult to predict TO of the culprit artery in NSTEMI patients due to the lack of classic electrocardiograms (ECG) findings. Attempts have been made to find a marker that reliably predicts the presence of TO in patients with non-ST-segment acute coronary syndrome (NSTE-ACS)-though without success. In this study, we evaluate the capacity of high-sensitivity cardiac troponin T (hs-cTnT) to predict acute TO of a coronary artery in patients presenting with NSTE-ACS.

| Study outcomes
The primary outcome was to assess the diagnostic accuracy of hs-cTnT to predict acute TO in patients with NSTE-ACS.

| Diagnostic adjudication
The final diagnosis was adjudicated for all patients by independent cardiologists, with discrepancies resolved until a consensus was

| Data collection and follow-up
The baseline demographics, type of presentation, and hospital outcomes were recorded. All available clinic charts, (ECG, holter monitors, and cardiac imaging were reviewed. All the patients included in this study were followed-up during hospitalization and evaluated for the presence of myocardial infarction, recurrent angina, stroke, and allcause mortality.

| Blood sampling and laboratory methods
Venous blood samples were drawn upon arrival to the emergency department via a peripheral venous line and immediately processed.
The Elecsys Troponin T-high sensitive assay (Roche Diagnostics, Risch-Rotkreuz, Switzerland) was used to measure hs-cTnT concentrations with a limit of blank and limit of detection at 3 and 5 ng/L respectively, an imprecision corresponding to 10% coefficient of variation at 13 ng/L, and the 99th percentile upper reference limit from healthy individuals defined at 14 ng/L. 11

| Determination of coronary occlusion
The type of coronary artery lesion was determined according to the American College of Cardiology/American Heart Association (ACC/AHA) classification. 12 The culprit vessel was identified based on the findings of coronary angiography, 12-lead ECG, 2-dimensional echocardiogram, and noninvasive stress test, as appropriate. All patients underwent PCI within 3 days of admission. Coronary flow pre and post-PCI was classified according to the Thrombolysis in Myocardial Infarction (TIMI) risk score. Patients were divided into two groups (TO and Non-TO group) based on the presence of pre-TIMI flow; pre-TIMI flow 0 (TO group), and pre-TIMI flow ≥1 (non-TO group). The differentiation between acute and chronic TO was based on the following factors: morphology of the occlusion (presence of a fresh thrombus, bridge, and ipsi-or-contralateral collaterals), the ECG recording, echocardiographic findings, and prior documented acute coronary events in the same territory. Univariate and multivariate logistic regressions were used to assess the predictive accuracy of hs-cTnT to predict acute TO. A two-sided P-value of less than 0.05 was considered statistically significant.

| RESULTS
A total of 1011 patients were identified who met the inclusion/exclusion criteria. The mean age was 67.12 SD 13.18 years, 74.1% were male, 26.7% had a history of coronary artery disease, and 8.9% had undergone coronary artery bypass graft surgery ( Table 1). The adjudicated diagnosis was NSTEMI in 608 (60.1%) patients and unstable angina in 403 (39.8%) patients. The median Global Registry of Acute Coronary Events score (GRACE) risk score of the population was 118 (IQR: 105-131) and the median TIMI risk score was 3 (range: 2-4). The median GRACE risk score was significantly higher in the TO group of patients (131 vs 117; P = 0.032) ( Table 2). The median hospital stay was 4 (IQR: 3-5.3) days.
Angiographic parameters are summarized in Table 4  The prevalence of acute coronary occlusions in NSTEMI patients varies from 19% to 30%. 13 In our study, the prevalence of acute occlusions was 7.3%, which could be due to the fact that our population was at a lower risk and included unstable angina patients than the other published series. In Khan et al's meta-analysis to estimate the difference in outcomes between TO and non-TO patients with NSTEMI, 9 the right coronary artery was occluded in most cases (40%) followed by the circumflex artery (33%). In our study, the circumflex artery was the most commonly involved vessel.