High-sensitivity Troponin T as a predictor of coronary anatomic complexity due
to SYNTAX score in patients with acute coronary syndrome without ST elevation
ÁLVARO ETCHEPARE, SANTIAGO ORDOÑEZ, FLORENCIA MANDÓ,
JOAQUÍN J. JARMA, IVÁN E. CHILLIK, VICTORIA GALIZIA BRITO, JUAN P. COSTABEL
Instituto Cardiovascular de Buenos Aires (ICBA), Argentina.
Buenos Aires, Argentina. E-mail
Recibido 18-OCT-2018 – ACEPTADO después de revisión el 19-NOV-20118.
There are no conflicts of interest to disclose.
High-sensitivity troponin T (HsTnT) and SYNTAX score (SS) are significant prognostic tools in patients with coronary heart disease. Knowing the coronary anatomy has an implication in patient management regarding antithrombotic strategy and revascularization. Objective: The aim of the study is to find an association between HsTnT and the severity and complexity of coronary anatomy measured by SS in patients with acute coronary syndrome without ST elevation (NSTEACS). METHODS: We conducted an observational, descriptive, retrospective analysis in 1011 patients with diagnosis of NSTEACS between December 2013 and December 2016. Inclusion criteria required patients to have an available coronary angiography report. HsTnT was measured at hospital admission and repeated three hours later; the peak value was taken into account. RESULTS: Of the studied population, the mean SS was 13.3. 86 patients (8.5%) had SS >32. Mean hsTnT at admission in the group with SS <32 was 15 (11-40) y hsTnT at 3 h was 17 (11-89), while in the group with SS >32 was 435 (258-756) and 657 (358-1026), respectively. In 104 patients, we observed left main coronary disease (10.3%) and in 168 multiple vessels disease (16.4%). The AUC of hsTnT as a predictor of complex coronary anatomy was 0.93. An hsTnT value of 280 ng / L was selected as the cut-off point for the prediction of high-risk STX, yielding 85% sensitivity and 86% specificity. In the multivariate analysis, hypertension OR 3.17 (CI 95%, 1.23 – 8.18; P = 0.017), ejection fraction OR 0.95 (CI 95%, 0.92 – 0.97; P = 0.001) and hsTnT OR 1.05 (CI 95%, 1.004 – 1.007; P = 0.001) show association. CONCLUSION: In patients with NSTEMI, hsTnT demonstrated a satisfactory performance for predicting complexity of the coronary anatomy evaluated by STX.
Troponin. Syntax score. Acute coronary syndrome without ST elevation.
The syntax score (SS) is an angiographic tool used to quantify the extension, severity and complexity of coronary anatomy . It is an independent predictor of morbidity and mortality in the short and long term in patients that present both with chronic stable angina (CSA) and with acute coronary syndrome [2-4]. Its use is recommended by clinical practice guidelines to decide between angioplasty (PTCA) with drug-eluting stent or myocardial revascularization surgery (MRS) .
High-sensitivity cardiac troponin T (hs-cTnT) is the preferred biomarker for the diagnosis of acute myocardial infarction (AMI). The peak of hs-cTnT has been associated to an increase in mortality, all-cause mortality, and adverse cardiovascular events in the short and long term in patients with acute coronary syndrome [6,7]. In patients with unstable angina (UA), the highest peak of troponin correlates to three-vessel disease and lesions with major degree of stenosis .
The aim of this study is to determine the ability of hs-cTnT to predict complex coronary anatomy measured by SS.
MATERIALS AND METHODS
A retrospective study was conducted. It was a single-center study carried out in the Service of Cardiology of the Instituto Cardiovascular de Buenos Aires (ICBA). Patients older than 18 years, admitted with diagnosis of non-ST segment elevation acute coronary syndrome (NSTEACS), were included, in whom their coronary anatomy was studied by coronary angiography. Patients were excluded when presenting tachyarrhythmias at the time of presentation, cardiorespiratory arrest upon admission, creatinine clearance estimated by MDRD <30 ml/min and ST-segment elevation acute coronary syndrome.
All patients signed an informed consent to participate on the study. The study followed the principles of the Helsinki declaration and was approved by the Committee of Education and Investigation and Ethics of our institution.
The clinical characteristics of patients were recorded, including cardiovascular risk factors, cardiovascular background, and physical examination data, as well as the clinical form of presentation and in-hospital evolution.
hs-cTnT was measured by the Roche company method, with the Elecsys analyzer, upon admission and 3 h later, and the maximum value was considered. A positive value was defined as hs-cTnT >14 ng/l.
The severity of the coronary lesions was assessed in at least three projections in all patients. All angiographic variables belonging to the Syntax score were reviewed by at least two experienced cardiologists that were blind for this study. SS was estimated by the software supplied by the Syntax Score Working Group in the web page www.syntaxscore.com The patients were divided according to the SS into a low-intermediate complexity (SS <32) and high complexity (SS >32).
Acute myocardial infarction (AMI): increase or decrease of hs-cTnT values with at least one value above the normal reference limit for 99% of the population in two samples, associated to precordial pain, new alteration in cardiac motility in imaging tests, alterations in ECG compatible with ischemia (new ST-segment or T-wave shift, new Q wave or new left bundle branch block) or intracoronary thrombus image in coronary angiography .
Diagnosis of complete left bundle branch block (CLBBB): QRS >120 ms, dominant S wave in V1, wide and monophasic R wave in DI, aVL, V5-V6, absence of Q wave in D1. V5-V6 and R-wave peak time in V5-V6 >60 ms.
Ischemic changes: in ECG, in absence of CLBBB:
New ST segment rise: >0.1 mv in2 or more contiguous leads, except V2-V3, where the following cutoff points are applied: >0.2 mv if male patient is older than 40 years; >0.25 mv if male patient is younger than 40 years; and >0.15 in female patients.
New drop: in plane or with descending slope in ST segment >0.05 mv in 2 or more contiguous leads.
T-wave inversion: >0.1 mv in two or more contiguous leads .
Unstable angina: ischemic symptoms (precordial pain or equivalent symptoms, such as dyspnea or syncope), with or without ECG changes and no hs-cTnT elevation. At least one of the following criteria should be present: a) angina in rest of more than 20 minutes of duration; b) angina having started less than 3 months before; c) recent increase in functional class of the Canadian Cardiovascular Society (CCS) classification at least until III, associated to the presence of stenotic lesions >70% in a coronary artery.
The categorical variables were presented as percentages and continuous variables as mean or median, with the corresponding standard deviation or interquartile interval as it corresponded. For their comparison, the Chi-square test or Mann-Whitney test were used respectively. For the analysis of normality, the Kolmogorov-Smirnov test was applied. To verify the relationship between hs-cTnT and high risk SS, the Pearson correlation coefficient was used. The analysis of multiple linear regression was applied to identify the independent relationship of hs-cTnT with SS. By the analysis of the receptor operating characteristic (ROC) curve, sensitivity and specificity were verified for hs-cTnT to predict SS >32. All statistically significant parameters in the bivariate analysis were included in the multivariate analysis.
All hypotheses were tested by two-tails and a p<0.05 was considered significant. Data analysis was conducted by SPSS for Windows 20.0 (SPSS Inc., Chicago, Ill).
RESULTS There were 1011 patients included consecutively; 608 presented as NSTEMI (60.1%) and 403 as unstable angina (UA) (39.9%). The average age of patients was 67.12±13.18 years and 74.1% were men. The average value of SS was 18±10 points.
From the total of patients, 87 (8.6%) presented SS greater than 32. In relation to the angiographic findings, 104 patients presented left main coronary artery lesion (10.3%) and 168 lesions of multiple vessels (16.4%).
The average age of patients with high SS was significantly higher in comparison to those presenting intermediate/low SS (p=0.001). The prevalence of hypertension and dyslipidemia was also higher in patients with high SS (p=0.001 and p=0.027, respectively). Additionally, left ventricular ejection fraction (LVEF) was significantly lower in patients with high SS (p=0.001). The patients that presented with a high SS, presented more frequently with NSTEMI; while patients with intermediate/low SS presented more frequently with UA. Table 1.
Table 1. Basal characteristics of the population
Age – years
Male gender - n
Hypertension - n
Dyslipidemia - n
Smoker - n
Former smoker - n
Diabetes - n
Peripheral vascular disease - n
Previous CAD - n
Previous coronary surgery - n
Left ventricular ejection fraction - % *
Grace Score - value *
hs-cTnT upon admission– ng/l *
Maximum value of hs-cTnT– ng/l *
Delta- ng/l *
hs-cTnT: high-sensitivity cardiac Troponin T. *Values expressed as median and interquartile range.
The median of hs-cTnT in the general population in admission was 17 ng/l (11-78.25); that of hs-cTnT at 3 h was 20 ng/l (11-172), with a delta hs-cTnT of 8 ng/l (1-59.25). The median of hs-cTnT upon admission in the group with SS <32 was 15 ng/l (11-40) and hs-cTnT at 3 h was 17 ng/l (11-89); while in the SS group >32 was 435 ng/l (258-756) and 657.5 ng/l (358-1026) respectively (p= <0.0001). hs-cTnT presented a suitable linear correlation with the SS value. (Figure 1)
Figure 1. Linear correlation between hs-cTnT upon admission and Syntax score value.
The area under the ROC curve of hs-cTnT upon admission to predict Syntax >32 was 0.93; of the peak value of hs-cTnT 0.92; and the delta hs-cTnT 0.86 (p<0.05) respectively (Figure 2). The best cutoff point to predict SYNTAX >32 was a value of hs-cTnT upon admission of 280 ng/l, with a sensitivity of 85% and specificity of 86%.
Figure 2. Area under the ROC curve of hs-cTnT upon admission, maximum value and delta
to predict SYNTAX score in patients with non-ST elevation acute coronary syndrome.
In the multivariate analysis, the following showed an independent association with the degree of complexity of coronary anatomy: hypertension OR 3.17 (CI 95%, 1.23-8.18, p=0.017); ejection fraction OR 0.95 (CI 95%, 0.92-0.97, p=0.001) and hs-cTnT upon admission OR 1.05 (CI 95%, 1.004-1.007 p=0.001). Table 2.
Table 2. Predictors of SYNTAX score>32 in multivariate analysis
Confidence interval 95 %
Hs-cTnT upon admission
This study showed that hs-cTnT is a good predictor of anatomical complexity for coronary lesions according to the SS in patients with NSTEACS, presenting a particular ability to detect those with a high anatomical complexity.
Knowing the complexity of the coronary anatomy has significant diagnostic and therapeutic implications, mainly at the time of defining the revascularization access. SS is one of the most widely used tools to quantify the extension, severity and complexity of CAD. Clinical practice guidelines recommend using it to define the best revascularization strategy, taking into account that while the SS value increases, revascularization by angioplasty has worse results, being inferior to surgical revascularization [1,4,11]. To stratify the risk of presenting complex coronary anatomy early, it would also be useful to decide on what antithrombotic therapy to use before coronary angiography, as in the case of patients with multivessel disease requiring surgery, using P2Y12 inhibitors delays the revascularization times and increases the risk of post-surgical bleeding [12-16].
In this experience, the value of hs-cTnT upon admission presented association with severe anatomical complexity in patients suffering acute coronary syndrome.
Ndrepepa et al, found a similar relationship in a group of patients with stable CAD . In their study, the association between the increase in hs-cTnT levels and the presence of CAD and its extension was independent from the traditional cardiovascular risk factors of NT-proBNP and C-reactive protein.
Yamazaki et al, in a similar population, showed that the value of hs-cTnT correlated independently to the severity of the CAD estimated by SS . In another study by Bhatt et al, they found a gradual increase until the peak of troponin by increase of SS . This difference was significant in multivariate analysis and was independent from angioplasty or stent placement during coronary angiography. These findings suggest that patients with greater anatomical complexity present a higher risk of myocardial ischemia, expressed in more troponin release.
The number of lesions is not the only factor involved in anatomical complexity. The SYNTAX study showed that the evolution of patients with multivessel CAD depended on the extension in number, the location of the culprit lesion, the presence of lesions in bifurcations, the presence of total occlusion and coronary artery calcification; all points taken into account in the SS [11,20,21]. All these factors are individually associated to troponin release, so the association of the marker to the total score should not be surprising. On the other hand, higher values of hs-cTnT in patients with NSTEACS and more complex coronary anatomy could be due to the presence of large atheromatous plaques, greater myocardial territory with compromised flow, as well as more inflammatory state in comparison to those presenting less complex anatomy.
The value of hs-cTnT turned out to be a good predictor of complex coronary anatomy, defined as SS of high complexity. Within the measurements of hs-cTnT, the results obtained upon admission presented the best prognostic value.
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