Cardiac troponins are among the most intensely investigated molecules in cardiology in the past several decades and are used as the primary biomarkers for the diagnosis of myocardial infarction (MI) since the year 2000.1 Numerous studies have documented that cardiac troponin assays are highly specific for myocardial rather than skeletal troponin I and T; cardiac troponin assays are highly sensitive to serum troponin elevations with modern assays increasingly sensitive to even minor serum troponin elevation (high-sensitivity and ultrasensitive assays), and of primary importance to clinical medicine, serum cardiac troponin elevations have strong prognostic implications in most patient subgroups encountered. In every clinical scenario and every subset of patients it has been examined, even minor serum cardiac troponin elevations strongly predicted both early and long-term complications and mortality, and higher troponins elevations predicted worse prognosis. Similar implications are accepted in high-risk patients undergoing major surgery.2–5 This was one of the major findings reported by van Waes et al.6 in this issue of the journal. They collected serum troponin I concentrations in 3224 patients in the first 3 days after major noncardiac surgery and found that the highest postoperative serum troponin I concentrations predicted 1-year mortality in a dose-dependent manner. However, this was not the only intriguing finding in their study. No less important was their observation that the vast majority (97%) of 715 patients with postoperative troponin I elevations were asymptomatic. A 12-lead electrocardiogram (ECG) was performed in only 59% of the patients with troponin elevations, but only 23% of those (13%) had changes suggestive of new ischemia, 3 (0.7%) with ST-elevations and 52 (12%) with new ST-segment depressions (≥1 mm). An attempt to implement a postoperative intervention protocol with a cardiology consultation in patients with troponin elevations resulted in a consultation in only 41%, and an intervention was deemed necessary in only 16% of patients with troponin elevations (38% of the patients who had cardiac consultation). The contradiction between the strong predictive value of even low-level troponin elevation and the very rare symptomatology and the limited chance to intervene and affect prognosis represents the enigma clinicians face in current practice.
It is first important to understand that cardiologists’ approach to a troponin elevation is different from ours as anesthesiologists. Cardiologists are trained to treat patients by signs and symptoms. Patients with no clinical signs or symptoms with certain notable exceptions (e.g., diabetes mellitus) are generally not felt to require treatment. Moreover, MI is defined by an increase and decrease in serum troponin in the setting of myocardial ischemia, that is either typical chest pain or new ECG changes suggestive of acute ischemia.1 Hence, troponin elevation without clear signs or symptoms of ischemia is not considered MI. Thus, there is an inherent problem with postoperative troponin elevation (PTE). These are usually clinically silent because patients are often sedated and treated with analgesics or they are mechanically ventilated due to sepsis or hemodynamic instability. Moreover, routine postoperative ECG monitoring with 3, or even 5 leads, is not sensitive enough to record and detect all ischemic ECG changes, let alone a randomly acquired, single 12-lead ECG once daily as is often reported in studies. We previously reported that symptoms attributable to MI occurred in a minority (18%) of patients undergoing vascular surgery with minor PTE. Ischemia longer than 15 minutes was detected in less than one-third of these patients on continuous, online 12-lead ECG monitoring, although the incidence of symptoms and ischemia on 12-lead ECG monitoring was more frequent in patients with higher levels of troponin.2 Similar results were obtained by others.5,7 Because serum troponin elevations in the first 3 days after surgery predict both early (30-day) and late mortality, regardless of symptomatology, researchers have tried to seize on this biomarker as an opportunity to treat and improve patients’ outcomes. However, the report by van Waes et al. highlights some open questions regarding PTE.
WHAT IS THE MECHANISM OF PTE?
In the report by van Waes et al.,6 <0.7% of the patients with PTEs had ST-elevation myocardial infarction (STEMI) on ECG. This conforms to prior studies using continuous perioperative 12-lead ECG monitoring in patients undergoing major vascular surgery, which showed the very rare occurrence of ST-elevation–type ischemia as opposed to the common postoperative ST-depression–type ischemia associated with troponin elevations.2,8 ST-segment elevation is the hallmark of acute coronary occlusion, mostly because of acute plaque rupture and coronary thrombosis. It is remarkable that many patients with significant coronary artery disease, and vulnerable coronary plaques, undergo major surgery accompanied by physiologic and emotional stresses and yet very few develop STEMI. STEMI is usually a clinically symptomatic event, especially after surgery, and requires immediate coronary intervention by either thrombolysis or percutaneous coronary intervention. In contrast, postoperative non–ST-elevation–type ischemia and subsequent troponin elevation are common and often asymptomatic. This led us to postulate in 2003 that prolonged, stress-induced ST-depression–type ischemia in patients with significant yet stable coronary artery disease is the main mechanism of postoperative MI (PMI).9 In 2007, the Universal Definition of MI10 was published categorizing, for the first time, the existence of 2 types of MI: type I is “spontaneous MI related to ischemia due to a primary coronary event such as plaque erosion, rupture, fissuring, or dissection,” whereas type II is “MI secondary to ischemia due to imbalance between myocardial oxygen supply and demand.” PMI is driven mainly by increased heart rates as a predominant mechanism.11 Anemia, hypoxemia, increased myocardial oxygen demand, ventricular over-/underload, systolic/diastolic dysfunction, and neuroendocrine responses to stresses of surgery all may contribute to the decreased ischemic threshold early after surgery. Pegg et al.12 reported (albeit in patients undergoing coronary artery bypass graft surgery) that postoperative serum troponin concentrations strongly correlated with the mass of new myocyte necrosis as assessed by delayed enhancement on cardiac magnetic resonance imaging. Hence, if we accept the notion that PMI is mostly type II MI, then asymptomatic PTE without clear evidence of ischemia is a subclinical type II MI or simply myocardial injury attributable to a prolonged imbalance between myocardial oxygen supply and demand.
WHAT IS THE ROLE OF ROUTINE SURVEILLANCE AND INTERVENTION FOR PTE?
The strong prognostic value of PTE has led various authors to advocate routine postoperative troponin measurements in high-risk patients undergoing major surgery, first for the purpose of postoperative risk stratification and also to minimize associated risks by an intervention.3,4,13 The potential cost-effectiveness of routine postoperative troponin surveillance and intervention using postoperative aspirin and statins14 or tight postoperative heart rate control with β-blockers15 has been investigated. Nevertheless, the question remains whether this added risk identified by PTE is modifiable. The answer to this question is still unclear. Data from one retrospective study in patients undergoing major vascular surgery suggest that patients with PTE in whom medical therapy (antiplatelet agent, β-blocker, angiotensin-converting enzyme inhibitor, or statin) was intensified postoperatively had better 1-year event-free survival compared with those without medical therapy intensification.16 One trial is currently still recruiting patients with PTE in an attempt to test whether the new oral anticoagulant dabigatran (in combination with omeprazole) reduces postoperative mortality.17 What van Waes and her colleagues discovered in their prospective study was that although surveillance for PTE is easy, an intervention in patients with significant PTE is difficult, let alone detecting the benefit from such an intervention, particularly in the absence of specific clinical guidelines. Cardiac consultation was obtained in only 41% of 715 patients with PTE, and only 111 (16%) had subsequent intervention that included any, even minor, change in cardiac, antihypertensive, or antiplatelet medications. In 23 (3.2%) patients with PTE, PMI was suspected in real time, 17 patients (2.3%) were transferred to the coronary care unit, 15 (2.1%) underwent coronary angiography, and 10 (1.4%) patients underwent subsequent percutaneous coronary intervention or coronary artery bypass graft surgery. What makes the intervention to improve risk in patients with PTE so difficult? First, the vast majority of patients with PTE are asymptomatic. Second, myocardial injury often is the result of concurrent serious noncardiac complication (massive bleeding, hypotension, and sepsis), and treatment must first be directed to prevent or treat the noncardiac complication.18,19 Third, myocardial injury may have happened long (hours or days) before the clinician was called to intervene, when the horses had already left the barn and myocardial damage had possibly occurred. In addition, PTE is possibly a marker of severe yet stable coronary artery disease that heralds later cardiac complications, and cardiologists are generally reluctant to intervene in patients with stable coronary artery disease during the unstable phase of the postoperative period. van Waes et al.’s study is yet another important effort in the long trail of attempts to solve the puzzle of PTE.
Dr. Martin J. London is the Section Editor for Perioperative Echocardiography and Cardiovascular Education for Anesthesia & Analgesia. This manuscript was handled by Dr. Steven L. Shafer, Editor-in-Chief, and Dr. London was not involved in any way with the editorial process or decision.
Name: Giora Landesberg, MD, DSc.
Contribution: This author helped write the manuscript.
Attestation: Giora Landesberg approved the final version of the manuscript.
Name: Martin J. London, MD.
Contribution: This author helped write the manuscript.
Attestation: Martin J. London approved the final version of the manuscript.
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