Editorial comment: ‘no time to die’—myocardial injury, troponins and long-term prognosis

Coronary artery bypass grafting (CABG) is inherently associated with some degree of myocardial injury due to myocardial ischaemia and reperfusion injury with cardioplegic myocardial arrest (in ‘on-pump’ CABG) and due to cardiac surgery and myocardial manipulation itself (in both, ‘on-pump’ and ‘off-pump’ CABG). In addition, myocardial injury may be associated with perioperative complications, reflected by an additional perioperative increase in cardiac biomarkers and, in particular, cardiac troponins. Thereby, a clear and strong correlation exists between the severity of myocardial injury on the one hand and the level of perioperatively released cardiac biomarkers in the patient serum on the other hand, and this is particularly evident for the highly sensitive and specific cardiac troponins. The clinically highly relevant question of the prognostic significance of such perioperative myocardial injury and, as a consequence, whether cardiac troponins are of prognostic significance in the follow-up period has been the subject of numerous studies in the past.

In fact, it is really only since the mid-2000s that the cardiac surgery community has been concerned with the biomarker performance and postoperative release dynamics of cardiac troponins following cardiac surgery and the potential associated postoperative outcome. The general tenor of the initial findings at that time was that an association existed between high troponin release and increased immediate postoperative mortality and morbidity [1]. Several large recent publications appear to confirm these findings for cardiac surgery [2] and more specifically for CABG surgery [3, 4]. However, a large proportion of these studies have historically examined heterogeneous patient populations and included different types of surgery and methods. Nevertheless, it is now known that different types and techniques of cardiac surgery are associated with quite different levels of troponin release and progression, which in turn makes it more difficult to compare outcomes or to designate universally applicable clinical, diagnostic and prognostic cut-off values for mortality and morbidity in the short term but even more in the long term [5, 6]. Furthermore, the rather diagnostic and definitional focus of many studies and the establishment of precise cut-off values, the clinical application of which was often impractical, prevented a consistent statement on the prognostic significance of postoperative cardiac biomarkers [7].

The subject of off-pump surgery in relation with perioperative cardiac troponin progression and its prognostic significance has received rather little attention in recent years. Kim et al. now focused intensively on this topic. The present paper published documented the postoperative cTnI-release in a cohort of 846 consecutive patients following off-pump CABG and another 150 patients following on-pump CABG and compared their postoperative short- and long-term outcomes of 2 groups of patients divided according to the 80th percentile of their postoperative troponin peak. The focus was on survival as well as major adverse cardiac and cerebrovascular event-free survival (MACCE). Documentation of cardiac biomarker measurement and surgery-related characteristics were performed separately for each type of cardiac surgery. Patients operated on using off-pump technique had a lower number of distal anastomoses and had a lower average postoperative troponin than patients operated on using the conventional technique. The latter was attributed to the different mechanisms of myocardial injury during surgery. Overall, there was no difference between the groups in terms of all-cause mortality [8].

With regard to the significance of postoperative cardiac troponins and, in particular, here in this work of troponin I for short-term mortality, the statement by Kim et al. in this this regard should be viewed critically in the context of the current literature. Many studies have reported a clear association between high perioperative troponin release and immediate postoperative mortality and morbidity [9, 10]. The findings of the present study however are most likely due to the low number of affected patients.

The clear association between lower long-term mortality and morbidity in patients with increased postoperative cardiac troponin I following off-pump CABG and its evidence in a large, homogeneous patient collective over an impressive period supports the prevailing opinion in the literature and strengthens the role of cardiac troponin as a postoperative prognostic factor in everyday clinical practice. The cut-off value, in this case the 80th percentile [4152 ng/ml (92 × URL) for all patients, 3342 ng/ml off-pump CABG, 8936 ng/ml on-pump CABG], is well above the limit of the fourth universal definition of myocardial infarction and is within the range of comparable studies [11].

The use of a cut-off based on peak-by-peak calculation is critical. On the one hand, there are difficulties in clinical application (retrospective view, different cTnI assays, laboratory-specific cut-off values); on the other hand, numerous studies have shown that not only the height but also the timing of the troponin rise and, above all, the total area under the perioperative troponin curve are more distinctly and more significantly related to patient prognosis [12, 13].

Like the results on the prognostic value for short-term mortality, the results on the prognostic significance of cTnI after on-pump CABG with cardioplegic myocardial arrest have to be considered in a more differentiated way. This study did not describe a significant association between elevated cTnI and death or MACCE in the long term [8]. Due to the very small patient cohort and the presumably low number of related complications, the results have to be critically evaluated. In this regard, however, the opinion of the well-established literature is inconsistent according to the current status [14].

In summary, the present study by Kim and co-workers shows a very clear significant association between strong postoperative troponin release following off-pump CABG and worse long-term prognosis. Besides that, the present study also shows that a higher troponin elevation based on the surgical technique (on-pump versus off-pump), aortic clamping and/or the number of distal bypass anastomoses does not necessarily mean a poorer prognosis. However, an excessive increase above the level of surgery-related injury has prognostic significance.

The present study also demonstrates and confirms the urgent need to revise the currently applicable cut-off values of the fourth universal definition of PMI [15]. The calculated cut-off values of this and other studies are far above the stated cut-offs and are exceeded postoperatively by most patients without the presence of perioperative myocardial infarction. A revised or even definition of perioperative myocardial injury and myocardial infarction in the context of cardiac surgery, integrating all its various types and surgical techniques, would be desirable to allow for more targeted and specific diagnosis and treatment in the future.

All in all, the present study confirms the prevailing opinion on the prognostic significance of cardiac biomarkers following cardiac surgery and their importance in the clinical setting. However, further studies, including new and more sensitive cardiac biomarkers, are needed to consolidate these findings so that new definitions and criteria can be established to further improve patient outcome and prognosis following cardiac surgery.

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