Prognostic Value of Preoperative Cardiac Troponin I in Patients Undergoing Emergency Coronary Artery Bypass Surgery With Non–ST-Elevation or ST-Elevation Acute Coronary Syndromes
Background— Cardiac troponin I (cTnI) is a highly sensitive and specific biomarker which has been shown to predict patient outcome pre- and postoperatively following elective coronary artery bypass surgery (CABG). Whether preoperatively elevated cTnI levels similarly predict the outcome in patients undergoing emergency CABG with acute myocardial infarction (AMI) is currently unknown.
Methods and Results— A possible correlation between preoperative cTnI and in-hospital mortality and major adverse cardiac events (MACE) was investigated in 57 patients with ST-elevation AMI (STEMI) in group 1 and 197 with Non-ST-elevation AMI (NSTEMI) in group 2, who were operated within 24 hours after onset of symptoms. Primary study end point was all-cause in-hospital mortality. Secondary end points were low cardiac output syndrome (LCOS) and hospital course. CTnI levels on admission were higher in group 1 compared with group 2 (7.1±1.8 versus 1.4±1.8 ng/mL; P<0.001). Overall in-hospital mortality was higher in group 1 compared with group 2 (14.3 versus 4.1%; odds ratio [OR], 3.9, 95% confidence interval [CI], 1.3 to 12.3; P<0.01). LCOS occurred in 16/57 (28.1%), and 18/197 (9.1%) patients, respectively (OR, 3.9, 95% CI, 1.7 to 8.8; P<0.001). Postoperative ventilation time, intensive care, and hospital stay were significantly longer in group 1 versus group 2. Multivariate logistic regression analyses revealed preoperative cTnI as the strongest independent predictor for in-hospital mortality (P<0.001) and MACE (P<0.001) in all AMI patients, regardless whether ST-elevation was included as an additional risk factor or not.
Conclusions— Preoperative cTnI measurement before emergency CABG appears as a powerful and independent determinant of in-hospital mortality and MACE in acute STEMI and NSTEMI.
Cardiac troponins (I and T) have not only fundamentally improved the detection criteria for acute myocardial infarction (AMI),1,2 but also enabled risk stratification in the non-surgical,3,4 as well as in various surgical settings.5–7 Several clinical studies revealed cardiac troponins as reliable and valuable biomarkers for the prediction of short- and long-term prognosis and the probability of death in patients with acute coronary syndromes3,8–10 and in the setting of percutaneous coronary intervention (PCI).9,11–13 In the setting of coronary artery bypass grafting (CABG), the relationship between the postoperative release of cardiac troponins and patient outcome has been well associated in several previous studies.5,14–16 Whether the preoperative extent of acute myocardial injury ranging from microinfarctions due to preexisting microembolizing unstable plaques up to non-ST-elevation AMI (NSTEMI) and ST-elevation AMI (STEMI), as measured by cTnI, similarly predict the surgical risk of patients undergoing CABG is currently unknown.
The present study therefore focused on the clinical significance of a single preoperative cTnI serum level before CABG and its predictive value for major adverse cardiac events (MACE) and in-hospital mortality in patients with acute STEMI or NSTEMI.
This study was a prospective single-center study including 254 consecutive patients, who underwent first-time isolated emergency CABG due to acute STEMI (group 1) or NSTEMI (group 2) at the West-German Heart Center Essen between January 2000 and September 2005. We evaluated the association between the extent of preoperative cardiac troponin I (cTnI) serum levels before emergency CABG and the postoperative in-hospital patient outcome.
Study End Points and Definitions
Primary end points of the study were in-hospital mortality, defined as death from any cause within 30 days after CABG surgery or during the same time period of hospitalization, as well as postoperative MACE during the period of hospitalization including low cardiac output syndrome (LCOS), which was supposed with a postoperative cardiac index below 2.0 L/min/m2 or with a systolic arterial pressure below 90mmHg despite high-dose inotropic support (IV dopamine ≥8 μg/kg/min or dobutamine ≥6 μg/kg/min or epinephrine >0.1 μg/kg/min or norepinephrine >0.1 μg/kg/min), cardiopulmonary resuscitation (CPR), and new-onset ventricular arrhythmia.
Patients were enrolled into the present study, if they underwent an isolated emergency CABG procedure and a preoperative cTnI serum level had been obtained within 12 hours before surgery. Patients were classified into STEMI or NSTEMI, depending on whether they had ST-elevations on admission ECG or not. An acute STEMI was supposed to be present on admission with (1) ST-segment elevations in two contiguous leads (≥0.1 mV in lead I, II, III, aVF, aVL, V4–V6 or ≥0.2 mV in leads V1–V3) (2) with a positive cTnI level and (3) new onset of chest pain or accelerating chest pain within the previous 24 hours occurring at rest or with minimal exertion. An acute NSTEMI was supposed to be present on admission with (1) no ST-segment elevations on the ECG, (2) a positive cTnI level, and(3) new onset of chest pain or accelerating chest pain within the previous 24 hours. Patients were excluded from the study, if any of the following preoperative criteria were present: (1) new onset left bundle-branch block, (2) reoperations, (3) any concomitant heart surgery besides CABG, (4) any concomitant AMI complications. The study was approved by the Institutional Review Board and all patients gave their informed consent.
Standard cardiopulmonary bypass (CPB) technique was used with ascending aortic and two-stage venous cannulation. During CPB, moderate hemodilution (hematocrit 20% to 25%) with mild systemic hypothermia (>32°C) was maintained. Myocardial protection was achieved using antegrade and optional retrograde crystalloid cardioplegic arrest and additional topical cooling. Patients were postoperatively monitored with respect to arterial pressure, pulmonary pressure, and central venous pressure.
Troponin I Measurement
Venous blood samples were drawn from each patient preoperatively before surgery. CTnI was measured using a specific two-side immunoassay (Dimension Flex, Dade Behring GmbH, Marburg, Germany). The detection range for cTnI was 0.04 to 40 ng/mL, requiring further dilutions if necessary. The assays reference interval was 0.00 to 0.05 ng/mL. A cTnI value above 0.1 ng/mL was considered as abnormal.
Continuous variables are reported as mean± SD or as medians and interquartile range. Categorical variables are reported as number and percentages. An exact Pearson’s χ2 test was used in the univariate analysis of categorical data and a Mann-Whitney U test in univariate analysis of continuous data. Univariate and multivariate logistic regression analyses were performed to identify preoperative independent predictors for in-hospital mortality and MACE. All preoperative predictor variables that were identified as significant at a two-tailed nominal probability value of less than 0.10 in univariate regression analyses were then entered into a multivariate logistic regression analysis model. The interaction between ST-elevation and preoperative cTnI value was included into this multivariate model, if its probability value was less than 0.10. Receiver operating characteristic (ROC) curve analyses were applied to determine optimal cut-off values of cTnI for in-hospital mortality and to evaluate the predictive power of cTnI in comparison to the logistic EuroSCORE. A probability value less than 0.05 was considered to indicate statistical significance. All statistical analyses were performed using the SPSS software (SPSS Inc., Chicago, IL, USA) and logistic regression analyses were performed using the SAS System®, version 8 (SAS Institute Inc., Cary, USA).
Statement of Responsibility
The authors had full access to the data and take full responsibility for its integrity. All authors have read and agree to the manuscript as written.
From January 2000 to September 2005, 254 patients with either acute STEMI or NSTEMI underwent emergency first-time isolated CABG surgery within 24 hours between symptom onset and revascularization at our institution. Preoperative characteristics and demographics of the patients were comparable between the groups (Table 1). Patients were significantly different according to their cardiac history and preoperative status, with different preoperative cTnI levels, angina class, previous MI and CPR, previous PCI and failed PCI, left main-stem disease, 3-vessel disease, LVEF, and a different Killip class between the groups as shown in Table 1. Preoperative risk stratification using the logistic EuroSCORE revealed significantly higher values in group 1 compared with group 2 (Table 1). The preoperative and intraoperative intra-aortic balloon pump was applied more frequently in STEMI compared with NSTEMI patients (P<0.001). The operative results were significantly different between STEMI and NSTEMI patients in regards to their CPB time, the frequency of combined use of ante- and retroplegia, and the reperfusion time (Table 2).
Postoperative in-hospital outcome, like postoperative ventilation time, as well as ICU- and hospital stay were significantly longer in STEMI compared with NSTEMI patients (Table 2). According to the primary study end points, STEMI patients had significantly higher all-cause in-hospital mortality, and MACE occurred more often compared with NSTEMI patients (Figure 1). Comparing the preoperative cTnI levels with postoperative survival status, a significant difference within the STEMI as well as within the NSTEMI patients could be observed between survivors and non-survivors (Figure 2).
To evaluate preoperative predictors of in-hospital death for the entire AMI study population (STEMI and NSTEMI), a logistic regression analysis model was constructed. Several univariate factors like age, female sex, renal disease, failed PCI, LVEF, unstable angina, preoperative Killip class, ST-segment elevation, CK, as well as preoperative cTnI levels were significantly associated with in-hospital death. After adjustment using a multivariate logistic regression analysis model, only LVEF and the preoperative cTnI level were significantly predictive for in-hospital death. Analyzing the predictors for MACE, univariate factors were age, COPD, unstable angina, preoperative Killip class, as well as the preoperative cTnI level. Independent multivariate factors predicting in-hospital MACE were then unstable angina, as well as the preoperative cTnI level (Table 3).
After separation of the entire AMI study population into those with STEMI and NSTEMI, again, multivariate logistic regression analyses revealed preoperative cTnI as the strongest independent predictor for in-hospital death (OR, 1.22, 95% CI, 1.03 to 1.41; P<0.02) and MACE (OR, 1.29, 95% CI, 1.09 to 1.58; P=0.002) in STEMI, as well as the strongest independent predictor for in-hospital death (OR, 1.08, 95% CI 1.02 to 1.09, P<0.001) and MACE (OR, 1.11, 95% CI, 1.03 to 1.12; P<0.001) in NSTEMI patients.
The discriminative power of the preoperative cTnI levels for in-hospital mortality using the ROC curve analyses yielded an area under curve (AUC) of 0.77±0.07 for the entire AMI study population (STEMI+NSTEMI), 0.79±0.02 for STEMI, and 0.72±0.08 for NSTEMI. In contrast, ROC analyses of the EuroSCORE in the same patient cohort revealed a significantly lower predictive power with an AUC of 0.70±0.06 for all STEMI+NSTEMI patients (P=0.03), 0.74±0.02 for STEMI (P=0.04), and 0.69±0.08 for NSTEMI (P=0.01; Table 4).
The present study demonstrates that in a surgical population of AMI patients undergoing emergency CABG, the existence of preoperative acute STEMI or NSTEMI is associated with significantly higher in-hospital mortality within 30 days and a higher incidence of MACE, such as LCOS or the need for CPR, depending on the degree of preoperative cTnI serum elevation. A preoperatively elevated cTnI serum level was clearly identified as an independent predictor of risk even after adjustment for other confounding risk factors in a multivariate logistic regression model. Moreover, the present study is the first clearly demonstrating in a surgical acute STEMI/NSTEMI patient cohort, that a single pre-CABG cTnI level is the strongest predictor for death and MACE and therefore, can easily be used as an additional incremental and independent prognostic variable before emergency CABG surgery to initiate appropriate operative and perioperative treatment modalities either in STEMI, as well as in NSTEMI patients. By using ROC analysis, cTnI was also shown to be more powerful in predicting in-hospital death compared with the logistic EuroSCORE,17 in which the extent of acute myocardial necrosis has not been considered adequately so far. Therefore, the present study not only confirmed the observations of prior non-surgical and surgical studies in selected patients,18,19 but also extends them in some important ways: (1) not only the risk for in-hospital mortality, but also for postoperative MACE like LCOS, CPR, and severe ventricular arrhythmia was shown to be significantly increased with preoperatively elevated cTnI serum levels; (2) a preoperative cTnI threshold level for increased risk was identified; and (3) these observations were made in AMI patients undergoing emergency first-time CABG surgery differentiating between either acute STEMI and NSTEMI patients.
Elevated markers of myocardial cell necrosis, most notably cardiac troponins (T and I), have been shown to be associated with adverse outcome and increased mortality rates in patients with acute STEMI,11,12 but also minor elevations of cardiac troponins among patients with NSTEMI were demonstrated to go along with a higher risk of death and reinfarction.3,18 More pronounced by elevated serum levels of cardiac troponins on admission, indicating a more extensive myocardial injury, have been unequivocally demonstrated to predict a worse clinical outcome and a more complicated course following primary PCI for acute STEMI.11,12 Patients with acute coronary syndromes and elevated cTnI levels on admission were found to have a lower reperfusion rate, a lower success rate for primary PCI, but a higher risk for in-hospital death and congestive heart failure, and a higher incidence of long-term cardiac mortality and overall cardiac events.9,12 In the setting of cardiac surgery, both, preoperative cTnI was described as predictive for patient outcome in elective CABG patients,19 and postoperative cTnI was reported to be highly predictive in cardiac surgical and/or CABG patients5,14 to 16. Whether postoperative cTnI is likewise capable to predict outcome in AMI patients undergoing emergency CABG has not been answered so far and should be evaluated in the future.
The addition of a highly sensitive biomarker, such as cardiac troponins, indicating myocardial cellular necrosis at the time of determination may well enrich the battery of preoperative risk stratification models for patients undergoing CABG surgery. As shown by the results of the present study, the extent of preoperative cTnI elevation indicates the degree of myocardial cellular injury and thus, the patient surgical risk before emergency CABG.
Our study encompasses the experience at a single tertiary care medical center; therefore, the generalizability of our findings may not extend to all of the clinical centers performing CABG surgery. CTnI serum levels depend on many variables, including first of all the type of cTnI immunoassay test kit and additionally several differences in the preoperative management and treatment of AMI patients may result in different preoperative cTnI serum levels. Furthermore, the prognostic ability of our multivariate regression risk model has not been tested in a validation cohort. Finally, only the in-hospital (short-term) outcome is reported in the present study, whether a pre-CABG cTnI level also predicts mortality and MACE in the long-term is as yet uncertain.
The present study is the first suggesting that preoperative cTnI measurement can serve as an incremental variable of risk for in-hospital mortality and MACE in AMI patients with STEMI or NSTEMI. With rising preoperative serum levels of cardiac troponin I, the risk of mortality and MACE increases. Therefore, preoperative cTnI measurement – as the most sensitive and specific biomarker for myocardial injury – may provide important prognostic information and thus, should be taken into consideration for preoperative risk stratification to decide about the appropriate timing of surgical intervention in those patients.
Whether, after elevated preoperative cTnI level has been shown, certain preoperative management strategies (eg, IABP, timing to surgery, preoperative anticoagulation regime, etc.) may have a beneficial impact on patient outcome remains uncertain and has to be elucidated in further studies.
Presented at the American Heart Association Scientific Sessions, Dallas, Tex, November 13–16, 2005.
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