Because cardiac troponin is a sensitive and specific measure of myocardial necrosis, it is the preferred biomarker for use in the diagnosis of acute MI. Although an elevated troponin indicates myocardial necrosis, it does not always indicate MI. Thus, in the ICU setting, where elevated troponin is frequently observed, additional evidence of myocardial ischemia can be obtained by using a 12-lead ECG. In this single centre prospective cohort study of predominantly medical ICU patients, 47% of critically ill patients had at least one elevated troponin measurement but only 26% met diagnostic criteria for MI based on a typical rise or fall in elevated troponin measurements and ischemic changes on a 12-lead ECG, with ECGs performed as clinically indicated. Patients with MI had significantly higher troponin levels than did those without MI. Patients who were diagnosed with MI had twofold increased rates of ICU and hospital mortality. The presence of an elevated troponin measurement alone was not associated with adverse outcomes, but the presence of MI was independently predictive of hospital mortality.
The incidence and prevalence rates of elevated levels of troponin cited in the literature vary widely, ranging from 15% to 70% of patients [17
]. Recent studies have examined the frequency of elevated troponin levels excluding those patients with underlying coronary heart disease [3
]; a 55% prevalence of elevated levels of troponin was reported, of which 72% of patients with an elevated troponin did not have flow-limiting coronary artery disease based on stress echocardiography or autopsy. The variability in frequency rates observed in our study and other studies is likely due to the heterogeneous nature of ICU populations and the threshold at which a troponin measurement is considered positive. The current troponin threshold recommended by the ESC/ACC has been defined for noncritically ill populations, and whether this threshold differs in the ICU setting is unknown. Furthermore, the various troponin assays are not standardized and, although it is recommended that levels exceeding the 99th percentile be considered positive, this level varies according to manufacturer [20
It is important to recognize that although a considerable number of ICU patients have elevated troponin measurements, and elevated troponin measurements are specific for myocardial necrosis, troponin itself does not distinguish between ischemic and nonischemic etiologies of myocardial injury. Interpretation of elevated troponin levels in the ICU must be considered in the context of the patient's symptoms (frequently limited in the ICU) or correlated with ECG findings or other imaging modalities. Most studies have examined elevated troponin levels in the critically ill in isolation, and it is unclear what proportion of patients have actually suffered an MI. One study evaluated troponin with ECGs in 34 consecutive critically ill patients who were mechanically ventilated and underwent thoracic or vascular surgery [21
]. It found that 11 patients (32%) had elevated troponin levels, and ECGs were available in 10 patients. Four patients (12%) had ST-segment elevation or depression, meeting criteria for MI; three patients had nonspecific changes and three had no ECG changes. Another study used continuous 12-lead telemetry monitoring in 76 patients admitted with noncardiac conditions [6
]. An elevated troponin level was found in 12 patients (15.8%), and six of these patients had transient ischemic events (mainly ST-segment depression) on telemetry.
The importance of a diagnosis that does not alter a patient's prognosis is questionable. Therefore, potentially the most important reason to identify critically ill patients with elevated troponin as having an MI or not having an MI is that the prognosis of these patients may be different. In the noncritically ill population, elevated troponin levels are an independent prognostic marker for short-term and long-term outcomes in patients with acute coronary syndromes. In the ICU several studies have reported that elevated troponin levels are associated with adverse outcomes. Elevated troponin I is a predictor of mortality in medical-surgical ICU patients [17
], including those without acute coronary syndromes [3
], and in ICU patients with early sepsis [22
], acute exacerbations of chronic obstructive pulmonary disease [14
], pulmonary embolism [23
] and following cardiac surgery [24
]. In surgical ICU patients, troponin is a predictor of mortality and longer length of ICU and hospital stay [13
]. However, most studies have examined troponin alone and did not examine prognosis in relation to those patients who had associated ECG changes (i.e. patients with MI).
One retrospective study examined the degree of troponin elevation in relation to prognosis [13
], and among the patients with recognized MI mortality was 13.6% in those with moderate elevations of troponin I (2.0–10.0 μg/l) and 32.4% in patients with troponin I above 10.0 μg/l. Like our study, this was limited in that there was no screening; it had a retrospective design, and it was unclear how the diagnosis of MI was made. Although we found that MI was predictive of hospital mortality, it was not predictive of other morbidity outcomes, including the duration of mechanical ventilation and ICU and hospital stays. This may be attributable to the relatively small number of patients included in our study or it may be an artefact of the distribution of some early deaths in this cohort. Similarly, predictors of ICU and hospital mortality, including need for life-saving therapies (hemodialysis, mechanical ventilation), were not significant in the multivariable analysis, which may relate to the distribution of risk factors (hemodialysis being infrequent and mechanical ventilation being common) in a study of this size.
Identification of those critically ill patients with MI has several treatment implications. In noncritically ill patients, patients with elevated troponin levels and acute MI benefit from antithrombotic therapy [27
]. Critically ill patients who also have elevated troponin and acute MI would also be expected to benefit from these therapies, but those patients who have elevated troponin without MI may not benefit and in fact may be harmed. Furthermore, critically ill patients with ST-segment elevation MI should be distinguished from those with non-ST-segment elevation MI because the former warrants urgent revascularization (or thrombolysis, although this is not always an option for ICU patients). We did not detect differences in outcome in patients diagnosed with ST-segment elevation or non-ST-segment elevation MI, although our analysis was underpowered to detect such differences.
Not only has recognition of MI been poorly studied but also the impact of antithrombotic and anti-ischemic agents has not been well documented in these patients. In one study, surgical ICU patients with moderate elevations in troponin I (2.0–10.0 μg/l, and not necessarily diagnosed with MI) who were treated with β-blockers and aspirin were reported to have lower mortality than patients with the same range of troponin elevation who did not receive these therapies [13
]. However, findings from this retrospective study should be cautiously interpreted because selection bias might have resulted in patients who were less critically ill receiving β-blockers and aspirin (e.g. patients without a coagulopathy and not requiring β-agonist infusions).
The strengths of our study include use of a priori
definitions for MI, and duplicate assessment by two independent investigators to classify events. Determination not only of patients with elevated troponin levels but also of those with MI provides relevant information not previously reported. However, there are several important limitations to the study. First, although ECG has been reported to be more sensitive for detecting myocardial ischemia than conventional ICU monitoring [30
], the ECG itself has limitations. The conventional ECG is not very sensitive for detecting infarction in certain locations (posterior) [32
], and not all patients who have myocardial necrosis exhibit ECG changes [2
]. In addition, uninterpretable ECGs occur among patients who are pacemaker dependent or have left bundle branch blocks, in whom acute changes cannot be detected using a standard 12-lead ECG. A second limitation is that systematic screening of all patients with troponin and ECG recordings was not performed in this study, and hence we cannot determine the true prevalence and incidence of elevated troponin and MI. Finally, there is currently no consensus on the appropriate diagnosis of MI in critically ill patients, whose ability to communicate may be severely limited and in whom diagnostic tests have not been vigorously evaluated. Our results may have differed if we required two or more elevated troponin measurements to meet the biomarker criterion, or if we required two or more ECGs demonstrating evolving changes [5
The utility of screening for MI in the ICU population has not been studied. In view of the prognostic and possible therapeutic implications of establishing a diagnosis of MI in the critically ill, use of noninvasive tests – including troponin and ECG – may be a reasonable approach. In contrast to the noncritically ill population, limitations in the ability of patients to communicate ischemic symptoms and the use of vasopressors and mechanical ventilation are unique to the ICU and may require the use of alternate methods of diagnosis. However, we cannot recommend for or against systematic troponin screening based on our study. The appropriate use of these tests and other diagnostic methods, including echocardiography in a screening mode, must be properly evaluated in well designed prospective studies.