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Ann Thorac Surg 2000;69:435-440
© 2000 The Society of Thoracic Surgeons

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Original Articles

Troponin levels in patients with myocardial infarction after coronary artery bypass grafting

^a Department of Surgery, Montreal Heart Institute, Montreal, Quebec, Canada
^b Department of Laboratory Medicine, Montreal Heart Institute, Montreal, Quebec, Canada

Address reprint requests to Dr Carrier, Montreal Heart Institute, 5000 Belanger St E, Montreal, PQ H1T 1C8, Canada
e-mail: carrier{at}icm.umontreal.ca

	Abstract

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Background. The objective of this study was to evaluate serum cardiac troponin T and I levels in patients in whom electrocardiogram, myocardial scan, and serum CK-MB levels of the MB isoenzyme of creatine kinase indicated perioperative myocardial infarction (MI) after coronary artery bypass grafting (CABG).

Methods. We studied 590 patients who underwent CABG at the Montreal Heart Institute between 1992 and 1996. Postoperative cardiac troponin T levels (493 patients), troponin I levels (97 patients), and activity of the MB isoenzyme of creatine kinase, electrocardiograms, clinical data, and clinical events were recorded prospectively. The diagnosis of perioperative PMI was defined by a new Q wave on the electrocardiogram, by serum levels of the MB isoenzyme of creatine kinase higher than 100 IU/L within 48 hours after operation, or both.

Results. After CABG, 22 patients in whom troponin T levels (22/493, 4.5%) and 6 patients in whom troponin I levels (6/97, 6.2%) were measured had sustained a perioperative MI according to current diagnostic criteria. In these patients, troponin T levels higher than 3.4 µg/L 48 hours after CABG best detected the presence of perioperative MI, with an area under the receiver operating characteristic curve of 0.95, a sensitivity of 90%, a specificity of 94%, a positive predictive value of 41%, a negative predictive value of 99%, and a likelihood ratio of 15. Serum troponin I levels higher than 3.9 µg/L 24 hours after CABG confirmed the perioperative MI with an area under the receiver operating curve of 0.86, a sensitivity of 80%, a specificity of 85%, a positive predictive value of 24%, a negative predictive value of 99%, and a likelihood ratio of 5.

Conclusions. Serum troponin T levels higher than 3.4 µg/L 48 hours after CABG correlated best with the diagnosis of perioperative MI. Serum troponin T levels greater than 3.9 µg/L 24 hours after CABG also correlated with the diagnosis of perioperative MI, although a larger experience is needed to confirm the validity of the chosen cutoff value.

	Introduction

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Perioperative myocardial infarction (MI) after coronary artery bypass grafting (CABG) remains a serious complication with a high risk of early and late mortality [1]. Despite attempts to improve the detection of perioperative myocardial necrosis, new Q waves on the electrocardiogram (ECG) and elevated blood levels of the MB isoenzyme of creatine kinase (CK-MB) are still used to establish the diagnosis. Although new Q waves on the ECG suggest transmural infarction, minimal necrosis, and damage are not recognized with this approach. We suggest that current criteria used to diagnose perioperative MI underestimate the prevalence of this serious complication after CABG.

Newer markers, such as cardiac isoforms of troponins, could be more specific and sensitive indicators of myocardial necrosis, particularly in the postoperative period after cardiopulmonary bypass (CPB), mechanical manipulation of the heart, and skeletal muscle trauma from dissection of internal mammary arteries. Several studies [1–3] have suggested that cardiac troponin T and troponin I levels could be sensitive and specific markers of myocardial necrosis after CABG.

The objectives of the present study were twofold: to compare serum cardiac troponin T and troponin I levels with serial ECG and serum CK-MB activity in the diagnosis of perioperative MI and to establish threshold values for troponin T and troponin I that strongly suggest substantial myocardial damage and necrosis 24 to 48 hours after CABG.

	Material and methods

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From 1992 to 1996, 590 patients who underwent elective CABG at the Montreal Heart Institute were prospectively studied to evaluate myocardial protection with intermittent warm or cold blood cardioplegia [4] or with antegrade versus retrograde administration of blood cardioplegia [5]. All patients gave informed consent, and the study protocols were approved by the institutional review board. Patients with any of the following criteria were excluded: operation within 7 days of an acute MI; emergency operation for acute coronary occlusion at angioplasty; emergency surgical procedures performed outside normal working hours; coronary bypass operations associated with any other cardiac surgical procedures; patients older than 75 years; and patients with preoperative renal dysfunction serum creatinine level greater than 200 µmol/L.

Surgical technique
Internal mammary artery and saphenous vein grafts were used in all patients. Proximal graft anastomoses to the aorta were performed with partial occlusion of the ascending aorta. During CPB, moderate hemodilution with hematocrit level maintained between 20% and 25% and mild systemic hypothermia with a core temperature of 33°C were used.

Myocardial protection
The cardioplegic solution was infused through a 14-F double-lumen needle (Medtronic Inc, Grand Rapids, MI) in the ascending aorta or through a 14F retrograde coronary sinus catheter with a self-inflating balloon (Research Medical Inc, Midvale, UT). The cardioplegia infusion set (CardioMed Supplies Inc, Gormley, ON, Canada) consisted of two inflow lines for mixing the crystalloid solution with blood from the arterial circuit at a ratio of 4:1. The crystalloid cardioplegic solution consisted of 1 L of Ringer’s lactate containing either 80 mmol (high K) or 32 mmol (low K) of potassium, 20 g of mannitol, 80 mg of lidocaine hydrochloride, and 1.9 mL of 8.4% sodium bicarbonate solution to obtain a pH of 7.4.

After the cross-clamping of the ascending aorta, cardioplegic arrest was achieved in all patients by antegrade coronary infusion of 300 mL of high-potassium solution over a period of 3 to 5 minutes at a perfusion pressure not exceeding 250 mm Hg in the infusion line and at the same temperature as the CPB perfusate (33°C, warm cardioplegia). Diastolic arrest was usually obtained before termination of the initial infusion. Thereafter and for the remainder of the procedure, intermittent bolus infusions of 200 to 300 mL of low-potassium solution were administered antegrade in the ascending aorta or retrograde through the coronary sinus after each distal anastomosis.

Markers of myocardial ischemia and diagnosis of perioperative MI
Blood samples for determination of the serum levels of total creatine kinase, catalytic activity of CK-MB, and troponin T levels were collected before the beginning of the operation and 1 hour, 3 hours, 6, 12, 24, and 48 hours after chest closure in 493 patients. Troponin I levels were measured 1 hour, 12 hours, 24, and 48 hours after chest closure in 97 patients. Electrocardiographic tracings were obtained the day before operation, on arrival in the intensive care unit, and on postoperative days 1, 2, and 3. The diagnosis of perioperative MI was based on the presence of two of the following criteria: new Q wave or disappearance of R wave on the postoperative ECG tracing; serum CK-MB activity greater than 100 IU/L 12 to 48 hours after operation; and a positive pyrophosphate myocardial scan. The last was performed only in the presence of an abnormal CK-MB increase without changes on the ECG tracings.

The serum creatine kinase level (normal range, 24 to 195 IU/L) and the CK-MB catalytic activity (normal range, 0 to 30 IU/L), after inhibition of the MM isoenzyme with monoclonal antibody, were measured by standard methods using a Hitachi 717 analyzer and reagents from Boehringer-Mannheim (Mannheim, Germany). The serum cardiac troponin T concentration (normal range, 0 to 0.02 µg/L) was analyzed by an enzyme immunoassay using first-generation reagents containing polyclonal antibodies and an ES300 analyzer from Boehringer-Mannheim. The serum concentration of cardiac troponin I was determined by immunoassay method with the Baxter Stratus analyzer (Miami, FL), which uses two monoclonal antibodies specific for cardiac troponin I (normal range < 0.5 µg/L).

Statistical analysis
Data were analyzed using Student’s t test for continuous variables and the ² test for discontinuous variables. Receiver operating characteristic curves were used to compare the performance of the biochemical diagnostic methods of perioperative MI and to help determine the appropriate cutoff value of the marker for MI. Sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio were calculated to analyze the diagnostic value of each marker. Using a logistic regression analysis, we studied the relation between MI, serum troponin T levels, and patient characteristics. A forward selection of variables with a p value of less than 0.15 was used for the multivariate analysis. Data are expressed as the mean ± the standard deviation. The analyses were performed using the NCSS 6.0 statistical system (NCSS Statistical Software, Kaysville, UT).

	Results

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Patient population
Four hundred ninety-three patients who underwent CABG were monitored with serum levels of troponin T after operation. Twenty-two patients (4.5%) showed evidence of perioperative MI according to ECG and CK-MB criteria. These patients had longer cross-clamp and CPB time, a longer hospital stay, and a higher rate of hospital mortality than the 471 patients without a perioperative MI (Table 1).

View larger version (12K): [in this window] [in a new window]   Fig 1. Serum levels of troponin T after coronary artery bypass grafting (CABG). Levels in patients with perioperative myocardial infarction (PMI) were higher 12, 24, and 48 hours after operation than in patients without PMI (p = 0.0001).

View larger version (11K): [in this window] [in a new window]   Fig 2. Serum levels of troponin I after coronary artery bypass grafting (CABG). Levels in patients with perioperative myocardial infarction (PMI) were higher 12 and 24 hours after operation than in patients without PMI (p = 0.0001).

View larger version (11K): [in this window] [in a new window]   Fig 3. Serum levels of MB isoenzyme of creatine kinase (CK-MB) after coronary artery bypass grafting (CABG). Levels in patients with perioperative myocardial infarction (PMI) were higher than in patients without PMI (p = 0.0001).

View larger version (21K): [in this window] [in a new window]   Fig 4. Receiver operating characteristic curves suggesting that serum troponin T levels 24 (trop 24) and 48 (trop 48) hours after coronary artery bypass grafting give the most accurate prediction of perioperative myocardial infarction. (trop 12 = level 12 hours postoperatively.)

View larger version (22K): [in this window] [in a new window]   Fig 5. Receiver operating characteristic curves suggesting that serum troponin I levels 24 hours (trop 24) after coronary artery bypass grafting give the most accurate prediction of perioperative myocardial infarction. (trop 24 and trop 48 = levels 24 and 48 hours postoperatively, respectively.)

	Comment

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Perioperative MI is a serious complication of CABG. Most authors have stressed the negative effect of perioperative MI on early and late survival after CABG. In this study, 3 patients (3 of 28, 11%) with a perioperative MI died during the hospital stay. Although Hodakowski and associates [6] suggested that perioperative Q wave MI does not affect 3-year survival after CABG, Force and colleagues [1] showed that patients with perioperative MI were more likely to have a cardiac event within 30 months after operation. Chaitman and coauthors [7] found that the 3-year survival averaged 85% of patients with perioperative Q wave MI compared with 95% of patients without such a cardiac event at operation. Thus, patients with perioperative MI after CABG carry a worse prognosis.

The various studies of the importance of perioperative MI used different diagnostic techniques to identify the event. In our study, a combination of perioperative Q waves on the ECG, elevation of perioperative CK-MB levels, and pyrophosphate myocardial scans were used because previous studies showed that a combination of methods improved the diagnostic accuracy and was predictive of a negative effect on late survival [8]. In an autopsy study, Van Lente and associates [9] suggested that CK-MB levels higher than 133 U/L 15 hours after operation established the diagnosis of perioperative MI with a sensitivity of 0.6 and a specificity of 1. Although the positive predictive value was 1 with a prevalence of perioperative MI of 10%, the suggested cutoff value of CK-MB alone was unable to identify 40% of patients with an autopsy-proved MI. Thus, the diagnosis of perioperative MI remains difficult, and the prevalence of this complication varies according to the method used to monitor the perioperative period. We suspect that the current diagnostic approaches for determining perioperative MI underestimate the true incidence of this serious complication.

Cardiac troponins I and T are new and more specific markers of myocardial injury. They have been shown to predict the risk of mortality and of cardiac events in patients with unstable angina [10–12], to estimate infarct size after reperfusion [13], and to mark cardiac injury, MI and perioperative myocardial ischemia with a high sensitivity [2, 3, 14–17]. Moreover, these markers are highly specific to the cardiac muscle, a characteristic that should improve the diagnosis of perioperative MI in cardiac surgery. Moderate elevations of troponins T and I also reflect minimal reversible myocardial damage occurring in most patients undergoing CABG.

In the present study, serum troponin T levels higher than 3.4 µg/L 48 hours after CABG were the most reliable indicators of perioperative MI; the area under the receiver operating characteristic curve was greater than the area at 12 and 24 hours, and the sensitivity, specificity, and negative predictive value were greater than or equal to 90%. A positive predictive value of 41% with serum troponin T monitoring suggests that ECG and CK-MB criteria underestimate myocardial damage during CABG. The likelihood ratio of 15 suggests that a patient with a troponin T value higher than 3.4 µg/L at 48 hours increases by a factor of 15 the chance of having sustained a perioperative MI compared with a patient in whom troponin T levels remain normal, highly relevant clinical information [18]. The multivariate analysis suggests that an increase of 1 µg/L in the serum troponin T level 48 hours after CABG increases the likelihood of perioperative MI with an odds ratio of 2.1. Moreover, patients with serum troponin T values greater than 3.4 µg/L at 48 hours after operation had a higher rate of hospital mortality (4% versus 0.7%), a greater number of postoperative complications, and a longer stay in the hospital. Because these best cutoff points were internally generated with the current data, we acknowledge the inherent bias of the approach and will have to test these cutoff points prospectively in a larger cohort of patients.

Although the number of patients was much smaller in the troponin I group, serum levels of troponin I higher than 3.9 µg/L 24 hours after CABG also correlated with a perioperative MI. Adams and associates [19] established the upper limit of serum troponin I values at 3.1 µg/L in a study of the diagnosis of perioperative MI after noncardiac surgical procedures, and Mair and colleagues [20] reported that all patients with perioperative MI after CABG had a peak serum concentration of troponin I that was higher than 4.5 µg/L. Clearly, measuring serum troponin I levels 24 hours after CABG could be of great interest, although we need a larger experience to better define the cutoff value.

In conclusion, the measurement of serum troponin T levels 48 hours after CABG gives the best definition of perioperative MI, correlates with a high rate of hospital mortality, and assesses a greater risk of postoperative morbid events. The ECG, myocardial scan, and CK-MB criteria underestimate myocardial damage after CABG.

	Addendum

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Currently we measure cardiac troponin T with third-generation reagents containing two monoclonal antibodies (Boehringer-Mannheim) and using human recombinant troponin T as a calibrator. The test is performed with an ELECSYS 1010 chemiluminescent instrument (Boehringer-Mannheim). According to our preliminary studies under these conditions, 36 to 48 hours after CABG, a blood level of troponin T lower than 0.65 µg/L indicates the absence of major perioperative myocardial damage, and a level higher than 1 µg/L correlates with perioperative MI.

	References

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