Introduction
Annually, over 200 million people undergo major non-cardiac surgery worldwide [
1]. Despite technical improvements and increased patient monitoring, these procedures currently remain associated with high mortality and morbidity. Overall 30-day mortality exceeds 2 %, and reaches 6 % in high-risk populations (e.g. certain vascular populations) [
2‐
6]. Over half of these deaths are attributable to adverse cardiovascular events [
3,
7].
Recognition of an adverse cardiovascular event in the perioperative phase is difficult. Typical anginal symptoms are often masked due of the use of strong analgesics (e.g. opioids), and changes on the electrocardiogram are predominantly subtle or transient [
3,
6,
8]. Moreover, the diagnostic value of cardiac biomarkers such as cardiac troponin and creatine kinase muscle and brain isotype (CK-MB) remains controversial in the perioperative period, since factors such as skeletal muscle damage, inflammation and renal insufficiency interfere with serum levels [
9]. An adequate and timely diagnosis is therefore frequently delayed, and subsequent therapy may not be initiated at all.
In order to improve early recognition of perioperative myocardial injury (PMI), thorough knowledge of its pathophysiological mechanisms is required. In this article we will elaborate these mechanisms, and review the available evidence concerning perioperative myocardial infarction (MI).
Discussion
The incidence of type I MI in patients who suffer a fatal perioperative MI ranges from 45 to 55 % (Table
3). This is not significantly different from the non-surgical patients with fatal MI or sudden cardiac death, in which type I MI represents 50–80 % [
23,
46,
47]. In patients with a clinical suspicion of acute coronary syndrome after non-cardiac surgery, type I MI is observed in 45–57 % (Table
3). This percentage is much higher in patients with a high likelihood of MI, such as patients presenting with ST-elevation ACS [
28]. Of note, the validity and generalisability of these results are retained due a number of limitations (Table
2).
First, the study populations and designs of the aforementioned studies are not interchangeable (Table
1). Dawood studied 42 patients with MI <30 days of elective or emergency surgery using a case–control design, whilst Cohen studied 26 patients with MI <72 h after elective surgery using a cohort design. Of note, the study populations and designs of the angiographic studies were even less interchangeable: Gualandro performed a prospective aetiological study that assessed the incidence of type I MI in patients suspected of ACS, whilst Berger performed a retrospective therapeutic study to assess the best immediate invasive strategy in patients with an (almost certain) perioperative MI (Table
1).
Second, the methods to define MI (Table
1) are heterogenic; Dawood and Cohen used a histopathological analysis (i.e. the gold standard), whilst the in-vivo studies used conventional coronary angiography (CAG). A CAG has high diagnostic accuracy for MI, yet a number of limitations have to be recognised [
48,
49]. For instance, its interpretation is primarily based on the assessment of significant coronary lesions. Yet, a significant stenosis is not a necessity for a type I MI, since normal angiographic findings have been reported in 4–31 % of non-surgical patients with acute MI [
48,
49]. In those cases, outward remodelling of an unstable atherosclerotic plaque may have only caused a slight, or even a non-existent coronary lumen reduction [
50]. The share of type I MI may thus be underestimated.
Third, the incidence of clinical signs and symptoms suggestive of MI varies between studies (Table
3); Cohen and Gualandro reported incidences of 42.5 % and 41 %, respectively. Berger reported anginal symptoms in 100 %, and Dawood did not provide any numbers. The high incidence reported by Berger reflects its methodological shortcomings to answer our clinical question. Moreover, it underlines the fact that its population does not fully correspond to the average population with a perioperative MI. The incidences reported by Gualandro appear to be consistent with a large prospective study that reported an incidence of ischaemic symptoms in patients with perioperative non-fatal MI of 38.1 % [
4]. However, Gualandro did not perform routine assessments of cardiac biomarkers and/or continuous ECG monitoring. PMI could therefore have been missed in patients using strong analgesics. As a result, a clinically moderate group was studied, and the incidence of type I may have been overestimated. This suggestion is supported by high numbers of multi- or three-vessel disease (Table
3). Of note, the overestimation may have been somewhat tempered by missing data from critically ill patients who died before the angiography was performed [
25].
Fourth, the incidence of coronary thrombus differs between the angiographic studies; Gualandro reported 7 % compared to 63 % reported by Berger (Table
3). The low incidence found by Gualandro may have been related to the long interval between the MI and the angiography (average delay of 5.5 days versus 0.5 days in Gualandro versus Berger, respectively), the use of statins, antiplatelet and anticoagulant agents, and a lower likelihood of a type I MI than Berger. All of these factors may have contributed to (spontaneous) thrombolysis. The diagnostic delay can be explained by the undesirability of coronary angiography in the (very) early postoperative period, which is a result of its invasive nature, and the necessity of administration of antiplatelet agents and heparin.
Furthermore, the share of non-ischaemic and extracardiac pathology may not be overlooked as a cause of PMI. Especially cardiac dysrhythmias and pulmonary embolisms are common after noncardiac surgery, yet—as with perioperative MI—frequently remain asymptomatic. Current studies tend to be biased toward symptomatic cases that represent a population with a worse prognosis. In case of pulmonary embolisms, this is underlined by a high incidence of impaired right ventricular function, which correlates with a higher risk of death within 3 months (hazard ratio 2.2 (95 % CI 1.4–3.4)) [
17]. Increased accessibility of computed tomography angiography (CTA) will lead to an increased recognition of (asymptomatic) PE [
51]. Yet, the clinical relevance of small asymptomatic perfusion defects detected by CTA is currently unknown and should be evaluated in the near future [
44].
Clinical signs and ECGs cannot guarantee early recognition of PMI, and the implementation of standard continuous ECG monitoring is difficult. Additional screening therefore appears to be indispensable. This creates a window of opportunity for routine postoperative assessment of biomarkers such as cardiac troponin (cTn), which has recently shown to be a strong and independent predictor of short- and intermediate-term mortality [
3,
19,
22]. Its diagnostic interpretation, however, can be troublesome due to the interference of renal dysfunction, cerebral pathology and inflammation [
9]. cTn can therefore not be used as hard evidence of myocardial injury. Yet, it can be used to stratify patients who could benefit from additional anticoagulant therapy or a percutaneous coronary intervention (PE/MI or MI, respectively). Non and minimally invasive modalities (i.e. CTA, MRA and echocardiography) should be accessibly used in the early postoperative phase to avoid the use of superfluous anticoagulant and antiplatelet agents that are a necessity during CAG. The most valuable diagnostic modality should be individually determined based on the patient’s type of surgery, medical history, clinical presentation and comorbidities (Table
6).
Table 6
Useful diagnostic modalities to determine the pathophysiology of PMI
CAG | Pro | Best diagnostic accuracy for in-vivo assessment of myocardial infarction. Gold standard. Option of immediate assessment of clinical significance of coronary stenoses with FFR. Also, immediate PCI is possible |
Con | Invasive, risk of iatrogenic coronary dissection. Not attractive in the early postoperative phase. Use of contrast fluid. Radiation exposure. Expensive |
IVUS | Pro | Assessment of both coronary lumen, and plaque morphology (e.g. atheroma). Assessment of unstable/vulnerable plaques; plaque rupture, erosion, and intracoronary thrombus. Especially useful in situations in which angiographic imaging is considered unreliable, such overlapping vessels that cannot be adequately assessed with CAG, and in case of outward plaque remodelling |
Con | Expensive, invasive, time-consuming. Only performed by specialised angiographers. Use of contrast fluid. Radiation exposure. Measurement difficulties in case of bifurcations |
OCT | Pro | Approximately 10 times higher resolution than IVUS. Well suited for plaque morphologies within 500 μm. Furthermore, similar to IVUS |
Con | Vessel occlusion by means of gentle balloon inflation, and vessel flushing with saline during imaging acquisition is required. Therefore, assessment of the left main coronary artery might not be desirable. Shallow penetration depth in comparison to IVUS. Not appropriate for evaluation of arterial remodelling. Furthermore, similar to IVUS |
Echocardiogram | Pro | Assessment of myocardial segmental wall kinetics, right ventricular kinetics, and valvular apparatus. No radiation exposure |
Con | Coronary and pulmonary arteries no visualised, variable image quality |
CCTA | Pro | Number and degree of coronary artery stenoses, coronary calcifications, aspect of coronary plaque. Possibility of obtaining coronary artery calcium score |
Con | Artefacts due to calcifications. Pulmonary arteries not or only partially visualised. Overestimation of stenosis degree in calcified plaques (blooming). Use of contrast fluid. Radiation exposure |
CTPA | Pro | Assessment of pulmonary arteries. Highly sensitive for PE |
Con | Diagnosis of small perfusion defects with unknown prognostic value. Coronaries and heart are not accurately visualised. Use of contrast fluid. Radiation exposure |
Cardiac MRI | Pro | Highly sensitive for MI. Assessment of myocardial contraction, and segmental wall kinetics. No radiation exposure |
Con | Coronaries and pulmonary arteries not or only partially visualised. Expensive, time-consuming. Use of gadolinium |
Cardiac adenosine stress MRI | Pro | Highly sensitive for MI. Assessment of clinical significance of coronary stenoses by generating chemically-induced myocardial ischaemia. |
Con | Coronaries and pulmonary arteries not or only partially visualised. Expensive, time-consuming. Use of gadolinium. Use of adenosine. Limited availability |
Furthermore, the additive value of preoperative cardiac imaging needs to be evaluated, since current clinical prediction models convey prognostic value, yet frequently fail to adequately predict PMI [
52,
53]. Addition of modalities such as a (coronary) CTA may improve prognostic values, and could lead to a better stratification of patients who benefit from additional preoperative or perioperative interventions [
54]. The relevance of such a selection is underlined by the fact that a reduction in cardiac events can be counterbalanced by an increased risk of cerebrovascular pathology or bleeding (e.g. in case of antiplatelet agents) [
4,
55].
Conclusion
Recognition of perioperative myocardial injury after non-cardiac surgery is difficult due to the masking of angina, and the subtlety or transiency of ECG abnormalities. Thorough knowledge of the pathophysiologic mechanisms is therefore essential. These mechanisms can be subdivided into four groups: type I MI, type II MI, non-ischaemic cardiac pathology, and non-cardiac pathology.
In patients suspected of a perioperative acute coronary syndrome. The incidence of type I MI is 45-57 %; this percentage is higher in those with a high likelihood of MI such as patients with ST-elevation ACS. Of note, the generalisability of this statement is limited due to significant study limitations.
Non-ischaemic cardiac pathology and non-cardiac pathology should not be overlooked as a cause of PMI. Especially pulmonary embolisms and dysrhythmias are a common phenomenon, and may convey important prognostic value. Implementation of routine postoperative troponin assessment and accessible use of minimally invasive imaging should be considered to provide adequate individualised therapy. Also, the addition of preoperative imaging may also improve stratification of high-risk patients that will benefit from pre- or perioperative interventions.