Asian Cardiovasc Thorac Ann 2000;8:19-23
© 2000 Asia Publishing EXchange Pte Ltd
Troponin T as a Marker of Infarction During Coronary Bypass Surgery
Tarek A Abdel Aziz, MD,
Mohamed A Ali, MD,
Donald G Roberts, MD, PhD,
Najib Al Khaja, MD, PhD
Department of Cardiothoracic Surgery
Dubai Hospital
Dubai, UAE
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For reprint information contact: Najib Al Khaja, MD, PhD Tel: 971 4 271 4444 Fax: 971 4 271 9340 Department of Cardiothoracic Surgery, Dubai Hospital, P.O. Box 7272, Dubai, UAE.
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Abstract
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To evaluate serum troponin T as a marker of perioperative myocardial infarction, 50 patients undergoing coronary artery bypass grafting were divided into 2 groups. Group A (14 patients) had serum creatine kinase MB-isoenzyme levels above 100 U•L–1 and electrocardiographic changes indicative of infarction. Group B (36 patients) had creatine kinase MB levels below 100 U•L–1 and no electrocardiographic changes. Blood samples were obtained preoperatively, 6 hours after aortic declamping, and on postoperative day 1, 2, and 3. Following surgery, all patients had increased levels of troponin T and creatine kinase MB. Troponin T was significantly higher in group A compared to group B at 6 hours, day 1, and day 2 postoperatively. Creatine kinase MB levels were significantly higher in group A compared to group B at 6 hours and day 1 postoperatively. The increased levels of troponin T in patients without myocardial infarction suggest that some operative myocardial damage occurred. Patients with perioperative myocardial infarction had significantly higher levels of troponin T up to postoperative day 2, whereas creatine kinase MB levels were almost normal by day 2. This suggests that troponin T may be used up to 2 days postoperatively for detection of myocardial infarction.
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Introduction
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In spite of procedures such as hypothermia and cardio-plegia, perioperative myocardial infarction (MI) still occurs frequently during cardiopulmonary bypass and may be difficult to diagnose in less severe cases.1 It represents an unsolved problem in the clinical considera-tion of prognostic implications.2 For diagnosis of perioperative myocardial infarction, changes in serum concentrations of creatine kinase and its myocardial-brain isoenzyme (CK-MB) are generally measured along with analysis of the electrocardiogram (ECG) or myocardial scintigraphy.3–5 Diagnosis of perioperative MI on the basis of serum CK-MB alone is not always accurate; surgical traumatization of muscle fibers can lead to false-positive results.6 The ECG pattern is sometimes difficult to interpret because of bundle branch block or rotation of the heart after the operation, so the presence of a small infarction may not be detected. It is also quite difficult to establish the presence of new infarction in patients who have experienced previous MI. Although the ECG lacks sensitivity to small infarctions, it is still useful when changes are noticed that arouse suspicion of altered myocardial status and to monitor progress of an established infarct and treatment of symptomatic arrhythmias.7
Recently, with the development of a new one-step enzyme immunoassay for cardiac troponin T (TnT) by Katus and colleagues,8 a more cardiac-specific and sensitive method for the detection of perioperative myocardial ischemic injury has become available.9 Cardiac TnT is one of the tropomyosin-binding proteins of the regulatory complex located on the thin myofilaments (actin, tropomyosin, and troponin). It differs from skeletal TnT by 6 to 11 amino acid residues and its detection in serum is highly specific as a marker for destruction of cardiac myo-cytes.10,11 This prospective study was designed to assess serum TnT as a marker of perioperative myocardial infarction in comparison to CK-MB and ECG.
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Patients and Methods
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Fifty patients undergoing coronary artery bypass grafting were studied. The Medical Research Committee of the hospital approved the study and informed consent was obtained from each patient. The mean age was 50.9 ± 1 years; there were 47 males and 3 females. Standard 12-lead ECG recordings were obtained preoperatively, on the day of surgery, and during the first 3 postoperative days. Each ECG was analyzed carefully by 2 independent cardiologists for: dysrhythmias; conduction disturbances; and new ischemic changes according to the Minnesota code, in the form of new Q waves, reduction of R-wave progression without clockwise rotation on chest leads, persistent ST-segment elevation above 2 mm, or T-wave inversion.12 Blood samples were collected preoperatively, on the day of surgery, 6 hours after declamping the aorta, and on postoperative day 1, 2, and 3. All samples were immediately centrifuged and the serum was kept at –80°C until analysis. The determination of CK-MB was carried out by the indirect immunological method of Chapelle13 using a test kit (Boehringer, Mannheim, Germany) and a Hitachi 707 analyzer (Hitachi Corp., Tokyo, Japan). The enzyme-linked immunosorbent manual method described by Katus and colleagues8 was used for determination of cardiac TnT in serum, using test kit reagents (ELISA; Boehringer, Mannheim, Germany).
Standard anesthesia and operative procedures were used in all patients. The patients were ventilated with oxygen after intubation. The chest was entered through a median sternotomy. The left internal mammary was harvested in all cases, as well as saphenous vein from the right leg. The aorta and the right atrium were cannulated; a single double-stage venous cannula was used to cannulate the right atrium. After adequate heparinization, cardio-pulmonary bypass was established using a membrane oxygenator (Cobe CMS 30HVRF; Cobe Cardiovascular, Inc., Arvada, CO, USA) and systemic hypothermia of 28°C to 30°C (rectal). The aorta was clamped and St. Thomas' Hospital no. 1 cardioplegic solution at 4°C was infused antegradely through the aortic root. The pericardium was irrigated with topical cold saline slush. All distal anastomoses were performed first during a single period of aortic crossclamping; the proximal anastomoses were performed after declamping, using a partial occluding clamp. After rewarming and deairing of the grafts, the patient was weaned from cardiopulmonary bypass. Decannulation was performed when complete hemodynamic stability was achieved and heparin was neutralized with protamine sulfate. Adequate hemostasis was ensured, chest tubes were inserted, the chest was closed, and the patient was transferred to the intensive care unit.
The patients were divided into 2 groups according to ECG changes and CK-MB levels after surgery. Group A (14 patients) had ECG patterns of ischemic myocardial injury and serum CK-MB levels above 100 U•L–1 (indicating extensive myocardial damage). Group B (36 patients) had no ECG changes and CK-MB levels below 100 U•L–1 (minimal myocardial damage).
Quantitative data were analyzed using the paired Student t test and qualitative data were analyzed using the standard error of difference between percentages (U test). A p value 0.05 was regarded as significant. Data were expressed as mean values ± standard error of the mean. The Spearman correlation coefficient (Z) was used to detect correlation between different values. A p value 0.05 indicates significant correlation. The statistical analysis and graphics were carried out with Stat-View SE + Graphics (Abacus Concepts, Inc., Berkley, CA, USA) software for Macintosh computers.
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Results
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The preoperative patient profile, risk factors, and angio-graphic findings where comparable in both groups (Table 1
). Operative parameters were recorded, including aortic crossclamp time, cardiopulmonary bypass time, and number of grafts; there was no statistically significant difference between the 2 groups (Table 2). At the end of cardiopulmonary bypass, the behavior of the myocardium was noted. The ability of the heart to take over from the machine was recorded as being difficult or easy with respect to spontaneous resumption of sinus rhythm or the use of direct current shock, inotropic support, or myocardial pacing (Table 2). The need for inotropic support (with dopamine in doses above 5 µg•kg–1•min–1) and direct current shock was higher in group A. Immediate postoperative complications were recorded in the intensive care unit. In group A, 2 patients required prolonged ventilation (> 24 hours), while in group B, 1 patient was explored for early postoperative bleeding. There was no mortality in either group.
Analysis of serum CK-MB levels (Figure 1) showed that preoperative samples were normal in both groups (normal range of CK-MB is 0 to 24 U•L–1). In the postoperative samples, the levels rose in both groups to reach peak values on postoperative day 1 (Group A: mean, 107.7 ± 2.1 U•L–1; range, 100 to 125 U•L–1. Group B: mean, 72.5 ± 1.8 U•L–1; range, 48 to 98 U•L–1). The CK-MB levels were significantly higher in group A at 6 hours after aortic declamping and on postoperative day 1 (p < 0.0012 and p < 0.0001, respectively). The CK-MB levels were normal in both groups on postoperative day 2 and 3.
Analysis of serum TnT levels (Figure 2) showed that preoperative samples were normal in both groups (normal range of TnT is 0 to 10 µg•L–1). In postoperative samples, the levels rose in both groups to reach peak values on postoperative day 1 (Group A: mean, 47 ± 6 µg•L–1; range, 29 to 100 µg•L–1. Group B: mean, 32 ± 3 µg•L–1; range, 12 to 100 µg•L–1). The TnT levels were significantly higher in group A at 6 hours after declamping and on postoperative day 1 and 2 (p < 0.02, p < 0.01, and p < 0.01, respectively). The correlation between serum CK-MB and TnT at the same sampling points is shown in Table 3. There was a strong correlation between CK-MB and TnT levels at 6 hours after declamping and in the day-1 samples.
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Discussion
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Perioperative MI is a complicating event that has a marked influence on outcome after open heart surgery. The great variation in the incidence of this complication reported in the literature may reflect differences in methods and criteria used for its detection. The lack of standard criteria for the diagnosis of perioperative MI, as well as the limitations of methods used for investigating the effectiveness of various cardioprotective measures, warrants the evaluation of potential new markers of myocardial injury in open heart surgery.
In this study, the large but transient increase in the circulating levels of both CK-MB and TnT in the first postoperative day reflects both reversible and irreversible myocardial damage, while the increased levels of TnT at day 2 and day 3 are most likely due to continued release of TnT from damaged myocardial cells. This type of cell injury is biphasic, there is an immediate disruption of homeostasis in the cell membrane with leakage of CK-MB and TnT (early phase), thereafter, elevation of TnT probably results from damaged myofibrils (late phase).7 This might explain why TnT levels on day 2 were high and still had good diagnostic value for perioperative MI.
The increased levels of CK-MB correlated well with the increase in TnT levels on the first postoperative day. This suggests that at this time, the two parameters might reflect the same pathophysiologic event. However, on post-operative day 2 and day 3, the levels of TnT remained elevated and appeared to be of diagnostic value on day 2, whereas the levels of CK-MB had almost normalized at that time. As shown in Table 3
, there was a strong correlation between CK-MB and TnT levels at 6 hours after declamping and on day 1, indicating that TnT leaked from the myocardial cells as early as CK-MB, which reflects cytoplasmic membrane damage. On the other hand, TnT levels were still high on day 2 and day 3 but there was no correlation with CK-MB levels at these times. This might indicate structural myocardial damage or cell death. Since TnT has a half-life of 2 hours, any sustained increase would suggest ongoing structural damage, and in the late phase, it probably indicates irreversible damage.14
The finding that patients with perioperative MI had higher levels of TnT agrees well with the results of many investigators. Katus and colleagues15 reported that patients with perioperative MI had a peak level of TnT on postoperative day 4. The groups of Eikvar16 and Triggiani17 reported that peak TnT levels occurred on day 1 in patients with and without perioperative MI. The reason for this discrepancy is not clear. The results of our study are in agreement with the 2 latter studies showing a peak level of TnT on day 1 in both groups. Although the values of TnT were highest on day 1, they were still high on day 2, which indicates more specificity regarding the diagnosis of irreversible myocardial damage.
Variables such as the extent of the surgical procedure, aortic crossclamp time, and the duration of cardio-pulmonary bypass have been reported to be higher in patients who suffered perioperative MI.18 Other factors known to be associated with myocardial damage during surgery are inadequate myocardial protection, poor coronary runoff, and technical problems. Disturbance of the coronary microcirculation by microemboli, reperfusion injury, or asymptomatic postoperative graft occlusion might cause myocardial damage as a consequence of global ischemia and surgical trauma.7 It would be of interest to quantify the amount of such myocardial damage.
ECG criteria were used in combination with CK-MB levels to identify patients with extensive myocardial damage. However, ECG criteria after open heart surgery as indicators of perioperative MI have been ques-tioned.7,16,18 The ECG sometimes lacks sensitivity for a small infarction. Rotation of the heart, implantation of a pacemaker, or an old MI can hide the typical pattern of a fresh perioperative MI. This should be considered when evaluating the ability of TnT to detect perioperative MI as defined by ECG criteria. The disadvantage of CK-MB is that it is not purely specific for the heart.4 The serum level of CK-MB is also affected by the duration of ischemic time and the washout effect after reperfusion.19–21 Frequent blood sampling in the first 24 hours is required to find the peak CK-MB level to estimate maximum myocardial damage.7 Cardiac TnT levels somewhat follow those of CK-MB as TnT is incorporated in the cytoplasm similarly to CK-MB. Thus, TnT levels are also affected by the washout effect after reperfusion. Therefore, Katus and colleagues14,22 recommend using the ratio of day 1 and day 4 levels to cancel out the washout effect.
One of the disadvantages of the antibody method of measuring TnT levels might be cross-reaction with TnT of skeletal muscle origin. Although the amino acid sequences of cardiac TnT are highly cardiac specific, the method used today allows cross-reactivity with skeletal muscle TnT. The cross-reactivity of the cardiac TnT assay with skeletal TnT is reported to be approximately 2%.14,22 However, in the presence of skeletal muscle damage, serum TnT may be falsely high as an indicator of cardiac damage.7
It was concluded from this study that troponin T is a very good diagnostic marker of myocardial structural damage. While CK-MB levels are helpful only in the first 24 hours, the prolonged presence of TnT in serum until postoperative day 2 could help in the retrospective diagnosis of perioperative MI. The findings of high levels of TnT at day 2 in patients without ECG evidence of perioperative MI might indicate false-positive cases. It would be of interest to evaluate these patients regarding cardiac functional status and long-term outcome and to assess other specific markers such as troponin I or myosin light chain I.
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References
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Abstract
Introduction
