Conundrums in Perioperative Myocardial Injury

More than 300 million non-cardiac surgeries are performed annually worldwide, and the mortality related to these surgeries is still higher than expected.^1,2 Since cardiovascular complications are important contributors to this mortality and, circa one third of patients with a perioperative myocardial infarction suffer from in-hospital death or hospital readmission in the first 30 days after discharge, the development of strategies to improve diagnosis and treatment is essential.³ Additionally, most of perioperative myocardial infarctions are asymptomatic. Therefore, without a systematic screening program with serial measurements of cardiac Troponin (cTn), these events are missed. Several studies have shown that the occurrence of acute myocardial injury, diagnosed by elevated cTn concentrations without fulfilling the criteria of the 4^th Universal Definition of Myocardial Infarction, is related to substantial increase in short and long term mortality after non-cardiac surgery.^4,5,6 Although the systematic screening with perioperative cTn for patients at risk of postoperative complications has been recommended by some Guidelines,^6-8 there has been resistance in broadly applying this strategy due to the lack of guidance regarding which patients should be screened, which criteria to use for the diagnosis of perioperative myocardial injury and how to manage these patients. In this elegant scientific statement by Ruetzler et al⁹ , the authors provided guidance to these important questions. In order to improve current perioperative patient care, it is important to understand how to apply and incorporate these new concepts in the clinical daily life of physicians.

First of all, it is essential to make the diagnosis of MINS (myocardial injury after noncardiac surgery) correctly, to avoid mistreating the patients. Not every cardiac troponin elevation after non-cardiac surgery fulfills the criteria of MINS. By definition, MINS is due to an ischemic etiology (in line with the etiology of a myocardial infarction type 1 or type 2). When assessing a patient with elevated postoperative cardiac troponin levels, it is essential to determine its etiology. The cause of elevated troponin concentrations can be classified in extra-cardiac (due to pulmonary embolism, sepsis or direct cardiac trauma during surgery) or cardiac (MINS, including myocardial infarction type 1 and type 2, arrhythmias or acute heart failure). It was shown that 13% of the elevated cardiac troponin concentrations are due to extra-cardiac causes, and circa 78% due to MINS.¹⁰ Below a series of examples are shown to better clarify which patients should not be classified as having MINS:

1. Case 1: 80-year old female patient presents with an elevated hs-cTn concentration of 65ng/l in the first day after a hip-replacement operation. In the computed tomography a pulmonary embolism was found. This case cannot be classified as MINS, once the cause of the troponin elevation was the pulmonary embolism, which should be treated accordingly.
2. Case 2: 52-year old man, who had been submitted to a colectomy due to a colorectal cancer, which caused a perforation with consequent septic shock, presents with a hs-cTnT of 70ng/l in the first postoperative day. This patient also does not have MINS, because the mechanisms of cardiac troponin release in patients with sepsis are not necessarily related to the presence of coronary artery disease and the treatment should focus in the main disease.
3. Case 3: 60-year old female patient in chronic hemodialysis program was submitted to an elective cholecystectomy. In the first post-operative day the hs-cTn concentration is 77ng/l. The preoperative hs-cTnT concentration was 76ng/l. This patient also could not be classified as having MINS, because there is no evidence of an acute rise and fall pattern, suggesting that this patient has a chronic myocardial injury.
4. Case 4: 65-year old man presents to the emergency department due to typical angina, the electrocardiogram showed ST-depression in the anterior wall and the initial hs-cTnT was 112ng/l. In the clinical history, he reports that he had been submitted to a femoropopliteal bypass 20 days before. This patient has clearly a type 1 myocardial infarction and should be treated accordingly. 99.4% of MINS occurs in the first three days after surgery, which is the period that the systematic screening using cardiac troponin is performed.

Second, as stated by the authors, there is still no consensus about the diagnostic thresholds of several cardiac troponin I assays currently available because the initial trials were performed using cardiac troponin T. In a recent study, we diagnosed perioperative myocardial injury and MINS using the high sensitivity cardiac Troponin I assay from Abbott in 2,455 patients undergoing non-cardiac surgery, applying the same criteria as in the VISION and PMI studies.^4,5 Acute perioperative myocardial injury and MINS were independently related to mortality and major cardiovascular events within 30 days and one year. These data reinforce the assumption that the results of the initial studies with hs-cTnT could be extrapolated to other cardiac troponin assays.¹¹

Third, after the diagnosis of MINS it is important to improve patient treatment, in order to avoid the short and long-term high rates of cardiovascular complications and mortality related to MINS. Although there is a lack of evidence regarding the management of patients with elevated cardiac troponin concentrations after noncardiac surgery, it is a consensus that the treatment should be tailored to the etiology. As MINS have by definition an ischemic etiology, additional cardiac testing to diagnose and determine severity of the coronary artery disease seems reasonable. The echocardiogram is widely available and could be useful to determine the presence of structural heart disease. The timing of a cardiac stress testing is still a matter of discussion. However, as the mortality of patients with MINS is already increased in the first month after surgery, it seems plausible to perform these tests as soon as possible. In patients with evidence of a type 1 myocardial infarction, treatment according current guidelines for acute coronary syndromes is reasonable. For all patients, statins and aspirin may be beneficial, as well as optimal management of cardiovascular risk factors. In the randomized MANAGE trial, the use of Dabigatran reduced a composite endpoint of major vascular events (vascular mortality, myocardial infarction, stroke, arterial thrombosis, amputation and venous thromboembolism) in patients with MINS.

In summary, the AHA statement by Ruetzler et al⁹, which standardized and clarifies the definition of MINS, also providing suggestions of how to manage these patients is definitely a major step in the field of perioperative myocardial injury and hopefully the first step to promote the broad use of troponin screening in patients at risk of cardiovascular complications, so that we could improve patient care, reducing cardiac complications and mortality of patients undergoing noncardiac surgery.