|Year : 2020 | Volume
| Issue : 4 | Page : 94-99
Relevance of Cardiac Troponin in Predicting Postoperative Myocardial Infarction
Manish Pangi, Satish Govindaiah, Vivekananda Siddaiah, Jedidaiah Samraaj
Department of Cardiac Surgery, Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bengaluru, Karnataka, India
|Date of Submission||31-Aug-2020|
|Date of Decision||07-Dec-2020|
|Date of Acceptance||13-Dec-2020|
|Date of Web Publication||24-Dec-2020|
Dr. Manish Pangi
Department of Cardiac Surgery, Sri Jayadeva Institute of Cardiovascular Sciences and Research, Jayanagar 9th Block, Bannerughatta Road, Bengaluru - 560 098, Karnataka
Source of Support: None, Conflict of Interest: None
Introduction: The aim of this study was to assess the validity of using early cardiac troponin (cTn) levels for the identification of postoperative myocardial infarction (MI) in patients undergoing off-pump coronary artery bypass (OPCAB) graft surgery, identify influencing factors, and determine optimal cut-off values for early identification. Materials and Methods: Patients undergoing OPCAB by a single surgical unit from January 2018 to January 2020 were included in this prospective study. Their preoperative and intraoperative characteristics were noted. The cTn was collected at 12 h and the in-hospital outcome was studied. Results: A total of 370 patients were included in the study. Eleven patients had MI determined by other criteria (2.9%), but 220 patients (60%) were identified using cTn consensus cut-off value, as per the universal definition of MI. This indicated significant mislabelling of coronary artery bypass graft-related MI and need for the recalculation to have a realistic cut-off value. The optimal cut-off levels at for identifying postoperative MI was found to be 1.8 ng/ml at 12 h, with a higher negative predictive value to exclude mislabeling. Using a cTn range, rather than a single cut-off value, would be more helpful. The factors causing significant mislabeled elevation of postoperative cTn were found to be preoperative high levels and intraoperative findings of iatrogenic hematoma secondary to suction stabilizer, surgical maneuvers for intramyocardial target vessels. Conclusion: The cTn levels were affected by the various patient and operative factors and measurements using higher cut-offs were needed to rule out MI. Certain factors peculiar to OPCAB were found to be significantly responsible. It will help identify patients needing earlier invasive re-intervention or focused intensive care.
Keywords: Cardiac troponin T, hematoma, high sensitivity test, intra-myocardial, myocardial infarction, off-pump coronary artery bypass grafting
|How to cite this article:|
Pangi M, Govindaiah S, Siddaiah V, Samraaj J. Relevance of Cardiac Troponin in Predicting Postoperative Myocardial Infarction. Res Cardiovasc Med 2020;9:94-9
|How to cite this URL:|
Pangi M, Govindaiah S, Siddaiah V, Samraaj J. Relevance of Cardiac Troponin in Predicting Postoperative Myocardial Infarction. Res Cardiovasc Med [serial online] 2020 [cited 2021 Jan 25];9:94-9. Available from: https://www.rcvmonline.com/text.asp?2020/9/4/94/304786
| Introduction|| |
Perioperative myocardial infarction (MI) is a significant cause of poor outcomes among patients undergoing coronary artery bypass surgery. It results in prolonged intensive stay, higher inotrope usage, re-interventional procedures and may even result in the death of the patient. Numerous criteria have been studied for the diagnosis of postoperative MI, including electrocardiographic, echocardiographic, angiographic, and biochemical markers. Using biochemical methods has the advantage of being widely available, cheap, and easy to use. The usage of specific cardiac biomarkers may result in early detection of perioperative MI. Serum cardiac troponin T (cTnT) has been proven to identify such patients. It may rise secondary to myocardial handling, inadequate myocardial protection, defibrillation also along with postoperative graft occlusion. It has been therefore proposed as part of universal consensus definition of MI, with type 5 denoting postoperative MI defined as elevation more than ten times the 99th percentile upper reference limit (URL) in patients with normal baseline values. Patients with elevated preprocedural cTn values, in whom the preprocedural cTn level are stable (≤20% variation) or falling, must meet the criteria for a >5 or >10 fold increase and manifest a change from the baseline value of >20%. In addition with at least one of the following, (i) Development of new pathological Q waves; (ii) Imaging evidence of loss of viable myocardium that is presumed to be new and in a pattern consistent with an ischemic etiology; (iii) Angiographic findings consistent with a procedural flow-limiting complication such as coronary dissection, occlusion of a major epicardial artery or graft, side-branch occlusion-thrombus, disruption of collateral flow or distal embolization. However, the causes for elevation are multifactorial and need for further research exists. In patients undergoing off-pump coronary artery bypass (OPCAB) grafting, avoidance of cardiopulmonary bypass (CPB), and the peculiar procedural handling may also affect the myocardial injury and interpretation of cTn. In addition, interpretation may also be confounded by preexisting elevated cTn levels, before the surgery. Patients with elevated cTn levels denoting ongoing myocardial injury/infarction tend to have a more adverse outcome. Intraoperative factors which could have the most important influence on outcome need to be studied for their actual impact on any analysis. The timing of cTn assay is also important, with tests done early have low sensitivity but those done later have a little practical benefit. Hence, the 12 h assay was chosen to have more clinical applicability.
| Material and Methods|| |
From January 2018 to January 2020, consecutive patients who underwent OPCAB surgery were included in the study. Exclusion criteria included concomitant procedures and emergency surgeries. All the cases were done by a single surgical unit in a specialized cardiac care institute. Patients had their preoperative and intraoperative findings recorded. Blood samples were taken at 12 h postprocedure. Routine electrocardiography and echocardiography were done, and angiography was done in selected patients. The criteria for establishing new-onset MI, other than biochemical markers, were as per the fourth universal definition of MI.
Troponin T (hs) was conducted on a Roche manufactured Cobas 8000® using electro chemiluminescence immuno assay. According to the manufacturer, it has a detection limit of 0.003–10 ng/ml. The cut-off criteria for defining MI were defined to be in excess of 14 ng/L.
All the data were analyzed, and statistics were performed using SPSS 23.0 Statistical Software (SPSS software incorporated Delaware USA). The data of 370 patients were analyzed in different parameters such as age, gender, body mass index, hypertension, diabetes mellitus, peripheral vascular disease, smoking history, renal dysfunction, etc., preoperative cTnT levels and operative factors. These parameters were compared and analyzed using Student's t-test (for Gaussian distributed data [normal distribution data]) and Chi-square test (Fisher's exact test). Receiver operating characteristic (ROC) curves were obtained for MI. P < 0.05 was considered significant.
| Results|| |
A total of 381 patients were enrolled in the study. Eleven patients had to be subsequently excluded as the timing of postprocedure blood sampling did not adhere to the protocol. The remaining 370 patients were available for the final study. There were 280 male patients (75%) and 90 female patients (25%). The patient characteristics were recorded, as shown in [Table 1].
Nearly 60% of cases (220 patients) had serum cTnT levels higher than the cut-off criteria (>14 ng/L), but only 11 patients had MI as documented by other criteria. Angiographic confirmation was available in only one patient, the remaining 10 patients were identified by electrocardiographic (new-onset q waves) and echocardiographic findings (new-onset regional wall motion abnormalities). Of these, 6 patients died during the postoperative period and the remaining 5 were discharged in stable condition, although with new regional wall motion abnormality and reduced cardiac function. The preoperative and intraoperative factors are shown in [Table 2] and [Table 3]. Preoperative high cTnT levels, intramyocardial target vessel requiring surgical scoring (using knife/cautery, traction sutures to remove overlying tissue) of myocardium for anastomosis and iatrogenic hematoma were found to be significant factors for elevated cTnT levels while not fulfilling other criteria of MI.
Among patients with new-onset MI, the area under the ROC curve was computed, as shown in [Figure 1]. The maximum likelihood estimation of a binormal ROC curve from continuously distributed test yield the sensitivity 89%, specificity 86, fitted ROC Area 94.5%, positive predictive value of 0.28 and negative predictive value of 0.98. The optimal cut-off point was found to be 1.8 ng/ml. This was 129 times the reference value. This value had a significant negative predictive value, which would be of practical use to exclude patients having a mislabeled MI.
| Discussion|| |
Perioperative MI has been said to be an important cause of adverse outcomes after coronary artery bypass graft (CABG).,, Early identification of which can help identify patients in need of re-intervention or more intensive monitoring. Accordingly, perioperative MI was defined in 2018 fourth universal definition of MI to include type 5 as post-CABG-related MI as the elevation of cTn by more than ten times the 99th percentile URL in patients with normal baseline values. Patients with elevated preprocedural cTn values, in whom the preprocedural cTn level are stable (less than or equal to 20% variation) or falling, must meet the criteria for a >5 or >10-fold increase and manifest a change from the baseline value of >20%. In addition with at least one of the following, (i) development of new pathological Q waves; (ii) Imaging evidence of loss of viable myocardium that is presumed to be new and in a pattern consistent with an ischemic etiology; (iii) angiographic findings consistent with a procedural flow-limiting complication such as coronary dissection, occlusion of a major epicardial artery or graft, side-branch occlusion-thrombus, disruption of collateral flow or distal embolization. Biochemical methods have an advantage in being cheaper, easier to interpret, and less utilization of scarce resources. Elevation of serum cTn, especially using hs assay, was found to have higher sensitivity compared to conventional cTnT measurements.,, Elevation of cTn can happen after routine CABG and could result from surgical handling, embolism, regional or/and global ischemia, and inadequate myocardial protection.,, Early elevation in cTn after is an independent predictor of hospital mortality, regardless of the mechanism of elevation or the additional diagnosis of MI. Certain other conditions not related to acute cardiac syndromes can also cause cTn elevation. Therefore, there is a need to differentiate routine elevation of serum troponin t levels from that resulting from perioperative MI. The choice of surgical technique can also influence cTn level, with the higher elevation of cTn during on-pump CABG., This could be secondary to using CPB, which can cause delayed clearance of cTn, especially in patients with reduced renal function. The effect of using OPCAB has not been studied. Since it obliviates the impact of CPB related delayed cTn clearance, it should avoid this confounding factor. However, the technique of OPCAB requires using stabilization usage, positioning, more varied surgical maneuvers, more chance of hemodynamic instability, surgeon's comfortability with the technique, all of which could influence cTn levels and hence their interpretation for diagnosing CABG-related MI. Our surgical unit has been preferentially using OPCAB, accounts for >90% of our CABG, which has similar long-term mortality, but better morbidity and shorter ICU and hospital stay.,, The level of rise with on-pump CABG has been studied extensively.,, There is a need to have similar predictors for OPCAB also. In our study with OPCAB patients, 60% had elevated cTnT (>14 ng/L) in the postoperative period at 12 h postsurgery.
The timing of cTn sampling has been studied, with peak concentrations of cTnT are seen at 24–48 h with levels at 48 h having the highest prognostic power. However, the ability to influence management decisions will be suspect, as the therapeutic window for postoperative MI lasts a few hours after the event. Post-MI, detectable levels of cTnT may be seen as early as 4 h; with higher sensitivity assay, it may be early as within an hour of injury. Jorgensen et al. in a study conducted on 99 patients undergoing on-pump CABG and serial cTnT levels, concluded that levels at 12 and 24 h would make the most clinical impact. Hence, our study protocol included sampling at 12 h to validate the applicability of cTnT hs measurements.
Regarding patient factors responsible for cTnT elevation, after on-pump CABG, old age and renal dysfunction were the most common factors. It was attributed to age-related renal dysfunction causing accumulation of cTnT.,, However, in our study, we did not find any association. We feel it could be because of our exclusive OPCAB patient group which by omitting cardio-pulmonary bypass, results in lesser renal impairment, thereby allowing for clearance of cTnT from the systemic circulation.,,,,
Our study group included 25% of patients who were cTnT positive at the time of surgery (cTnT > 14 ng/L). This elevation, secondary ongoing myocardial necrosis, was found to be associated with postoperative cTnT elevation. But other criteria as per the fourth universal definition of MI were not fulfilled. With the increasing use of CABG in acute or ongoing MI, more patients may have elevated preoperative cTnT, a factor to be considered while analyzing the postoperative cTnT levels. Mohammed et al. found prior MI, IABP, number of anastomoses and defibrillation use to be associated with cTnT elevation.
Our study, due to its prospective design, allowed us to accurately note intra-operative factors, which could influence the cTn level. We found a significant association between hematoma secondary to OCTOPUS suction use with postoperative cTn elevation. Avoidance of this iatrogenic injury may reduce the incidence of routine post CABG elevation. Intra myocardial target vessels, in which the target vessels are covered by muscle tissue, needs surgical technique modification to reach proper site and length for anastomosis. The maneuvers to remove overlying tissue include scoring on the cardiac surface using knife, low strength diathermy, gradual incising of surrounding tissue and placing tacking sutures to reach the target vessel. Both the factors were found to have a significant association in causing postoperative false elevation of troponin levels and would have resulted in mislabeling as postoperative MI. These factors, not previously studied, should be noted by the operating team to avoid unnecessary investigations triggered by cTn elevation with their attendant cost and complications.
In a study by Jorgensen et al., 99 post-CABG had their cTn I measured at serial intervals. They found 12 h and 24-h sample levels to have better utility for specific identification while utilizing the therapeutic window for any re-intervention if needed. They concluded that the current cut-off levels were inadequate and used ROC curves to suggest that optimal cut-off levels should be revised to 7970 ng/L at 12-h (266 times the URL) and 9950 ng/L for 24-h sample (331 times the URL). Ge et al. in their retrospective study of OPCAB patients with a normal postoperative course, also stressed need for revision of cTnT levels and found maximal levels at 24-h samples. They suggested that the multifactorial causes for the rise of troponin levels without causing MI, needed higher cut-off levels. Other studies had also proposed revision of optimal postoperative levels. Mohammed et al., in their study proposed 1.6 ng/ml to be the optimal cut-off level. They had a MI rate of 2% and suggested that trying to use cTnT levels to diagnose MI would be challenging. Using the consensus cut-off levels, would result in higher sensitivity but very low specificity, thereby resulting in little clinical utility. They postulated the utility of cTnT would be maximized if used as a negative predictive value to exclude impending major postoperative complications.
In this study, the MI rate was 2.9%, with a mortality rate of 1.63%. However, preoperative cTnT positive (>14 ng/L) cases formed a significant portion of our study group (25%), mirroring the likely clinical scenario that future cardiac surgical teams are likely to encounter. In addition, by including only OPCAB cases, we were able to get values specific for cases without the usage of CPB, which could also alter the interpretation of troponin values. This study is the first one to assess the influence of intra operative findings, which in turn could have significant effects on the elevation of postoperative troponin levels and their interpretation. By using ROC curves, we were able to get an optimal cut-off value of 1.8 ng/ml, which could let us identify patients requiring intensive monitoring or re-intervention. This could account for only 28% of cases with confirmed MI, suggesting low positive predictive value. However, using this cut-off level with a high negative predictive value will allow us to rule out cases at low risk for postoperative MI. Therefore, instead of using the consensus cut-off levels to diagnose post-CABG MI, using our revised cut-off level will help exclude it. It would be more practical to use a value range, with caveats for operative factors. This would reduce the high miscalculation rate and can be used for earlier clinical re-intervention if needed. It would result in better utilization of monitoring resources, especially invasive options (angiograms) and help in concentrating critical monitoring personnel and equipment to patients in need. As was seen in our study group, routine post-CABG angiogram is not a practically viable option. It is invasive with its own complications, result in the diversion of personnel and resources, increase cost of surgical care. Being a developing country with scarce resources, it is of paramount importance to avoid resource wastage. This more practical cut-off level would be helpful to avoid labeling of routine elevation of post CABG troponin levels (60% in our study) as type 5 MI (early adverse outcome) after CABG. Mislabeling as post CABG MI in the era of increasing accountability with regular surgical audit is of paramount importance in reducing the stress of already stressed operating surgeons. With the increasing comparative trials comparing per cutaneous coronary intervention versus CABG, there is an urgent need to avoid false interpretation of postoperative troponin elevation as an adverse outcome after routine surgery. It would be better for comparing different revascularization methods to have a more accurate picture which could be utilized for building real-time consensus recommendations so that patients and clinicians have a better understanding of likely outcomes.
While our study was designed to mirror the likely clinical scenario faced by present-day cardiac surgeons, it does have certain limitations. Our cut-off level of 1.8 ng/ml will have to be validated by a larger trial. The lower number of adverse outcomes in our study (2.9% postoperative MI and 1.63% mortality rate) and its likely further drop as the quality of care improves would necessitate increasing the cohort size to derive better analysis. More larger population-based multicentric trials would be ideal to assess the ideal cut-off value, however there appears to be valid argument for a more realistic consensus cut-off value range, especially with higher specificity to help exclude patients with low chance of post-CABG MI. This would help us to identify patients who may need earlier invasive interventions.
| Conclusion|| |
The cTn levels were affected by the various patient and operative factors and measurements using higher cut-offs were needed to rule out MI. Certain factors peculiar to OPCAB were found to be significantly responsible. It will help identify patients needing earlier invasive re-intervention or focused intensive care.
Obtained, 4 January 2018.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]