Perioperative Myocardial Infarction in Non-Cardiac Surgery – Why Measuring Troponin is Important?

Every year, more than 200 million adults undergo major noncardiac surgery.¹ 

Advances in noncardiac surgery have improved disease management and enhanced the quality of life for patients. Unfortunately, in the perioperative time frame several patients experience complications such as hemodynamic compromise, hypercoagulability, inflammation, sympathetic stimulation, and bleeding, which predisposes them to ischemic injuries. These disastrous consequences call for interventions and tools that may lower the risk of major perioperative cardiovascular events.² 

Interpreting troponin elevations after noncardiac surgery can help assess the risk of mortality and major vascular events.^1,3

This article focuses on the prognostic relevance of troponin elevation after noncardiac surgery with regards to myocardial injury after noncardiac surgery (MINS) and myocardial infarction in the perioperative setting.

Prognostic relevance of troponin elevation after non-cardiac surgery

Taking a look at the VISION study

The very first Vascular Events In Noncardiac Surgery Patients Cohort Evaluation (VISION) Study was a large, prospective, cohort study conducted to evaluate the relationship between perioperative troponin measurements and 30-day mortality in patients. The study included 40 000 patients (≥ 45 years) from North and South America, Africa, Asia, Australia, and Europe who underwent in-patient noncardiac surgery.¹

The study was representative of the patients who had surgery at the study centres. The patients may have received a general or regional anaesthetic, and underwent elective, urgent, or emergency surgery during the day or at night on a weekday or weekend. ¹

Patients had blood collected to measure cardiac TnT assay 6 to 12 hours postoperatively and on the first, second, and third days after surgery. An iterative Cox proportional hazards model was used to explore if there were TnT thresholds that independently altered the risk of 30-day mortality.¹ 

Rather than evaluating predetermined values (for example, the 99^th percentile), the authors statistically identified prognostically relevant TnT thresholds. The authors allowed the data to inform in the perioperative setting to determine if there were TnT thresholds that independently altered 30-day mortality.¹  

The results, which were published in JAMA in 2012, found that based on the identified peak TnT values, there were marked increases in the absolute risk of 30-day mortality: ¹ 

The study concluded that monitoring postoperative TnT measurements can enhance risk stratification after noncardiac surgery – the higher the peak TnT value, the shorter the median time to death. ¹

MINS and MINS Diagnostics Criteria – What aspects do we need to know?

MINS was first defined in a study published in 2014. The study published in Anesthesiology evaluated the diagnostic criteria, characteristics, predictors, and 30-day outcomes of MINS. The study used data from the VISION study and excluded patients who had evidence of a nonischemic troponin elevation, that is rapid atrial fibrillation, sepsis, pulmonary embolism, chronically elevated troponin.⁴ 

The study assessed patients for ischemic features (i.e., ischemic symptoms and electrocardiography findings) only if they met the threshold considered abnormal (i.e., TnT ≥0.04 ng/ml), which was the threshold being used by labs and which mandated ECG and clinical symptom evaluation. ⁴

The study found: ⁴

Elevated TnT + clinical features of ischemia = patients 5 X probability of 30 day mortality

Elevated TnT + No clinical features of ischemia = patients 3 X probability of 30 day mortality

Based on this, the authors defined MINS as not only including the universal definition of myocardial infarction but also isolated ischemic troponin elevations within 30 days after surgery.

In 2017, the second prospective cohort study (VISION study) of 21,842 patients by the same investigators using the hs-TnT assay, was carried out. The study found that after noncardiac surgery, the probability of death increases with an increase in peak high sensitivity troponin T value. Based on the results of this study, they defined MINS as postoperative concentration 20 to less than 65 ng/l with an absolute change of at least 5 ng/l or a postoperative concentration of at least 65 ng/l. ³

MINS is prognostically relevant myocardial injury due to ischemia that occurs during or within 30 days after non-cardiac surgery and is diagnosed by elevated troponins but does not require the presence of symptoms.³ 

COMPASS Trial vs MANAGE Trial – What do these trials add to prognostic relevance?

The COMPASS trial was a randomized controlled trial of patients with known coronary artery disease or peripheral artery disease, a group that requires aggressive medical management. The study compared aspirin alone (with rivaroxaban placebo) to the combination of rivaroxaban 2.5 mg twice daily and aspirin, or rivaroxaban 5 mg twice daily (with aspirin placebo).⁵

The MANAGE trial was a randomized controlled trial including 1754 patients who had MINS. The patients were randomized to receive dabigatran 110 mg orally twice daily or a placebo.⁶  

Looking at the baseline characteristics, one would predict that COMPASS patients had a worse prognosis at the start of these trials, as they also had a longer follow-up of 23 months compared to MANAGE which had 16 months. However, the actual story was different – The study outcomes (outlined below) highlight that patient in MANAGE with MINS had a worse prognosis than those in COMPASS.^5,6

Importance of Troponin Measurements after Noncardiac Surgery

In VISION, 93% of MINS occurred without ischemic symptoms and likely would have gone In VISION, 93% of MINS occurred without ischemic symptoms and likely would have gone unrecognized without troponin monitoring. This elevated postoperative hs-TnT without ischemic features were associated with an increased risk of 30-day mortality.³ 

In another study called POISE, which was a large perioperative beta-blocker trial that included 415 patients who had a myocardial infarction, two-thirds of patients were asymptomatic. In this study, cardiac markers were measured only at day 3 after surgery, hence, additional asymptomatic myocardial infarctions may have been missed. Thus, routine monitoring of troponin levels in at-risk patients is needed after surgery to detect most myocardial infarctions, which have an equally poor prognosis regardless of whether they are symptomatic or asymptomatic.⁷

Are all perioperative patients suitable for cardiac troponin measurements?

Bearing in mind the cost and practicality of implementation, one should target high risk individuals for cardiac troponin measurement.^8,9 

The VISION study economic analysis measured troponin daily for 3 days after surgery in patients ≥ 65 years or with a known history of atherosclerotic disease. The study found that the cost of screening for MINS is 10-fold lesser than the cost of screening for breast cancer or cervical cancer. ^8,9

It is recommended to measure troponin before surgery and the first two days after surgery to capture over 95% of the MINS cases. ⁹

So how should patients with MINS be managed?

In patients with MINS, physicians should consider initiating dabigatran 110 mg BID and ASA 81 and statin therapy.⁹

As evident from the MANAGE trial, among patients who had MINS, dabigatran 110 mg twice daily lowered the risk of major vascular complications, with no significant increase in major bleeding.⁶

Evidence from non-operative setting and observational data from a large international perioperative trial suggest that ASA and statin use is associated with a decreased 30-day mortality in patients who have experienced a perioperative myocardial injury. ⁹

Perioperative Troponin Elevation in Non-Cardiac Surgery – What do guidelines say?

The 2015 ESC/ESA guidelines on non-cardiac surgery recommends determination of serum biomarkers (NT-proBNP/BNP (brain natriuretic peptide), cardiac troponins) in high-risk patients. In such patients, determination of cardiac troponins at 48-72 hours after major surgery may be considered.¹⁰

The 2014 AHA guidelines on noncardiac surgery, recommends measuring troponin levels in the setting of signs or symptoms suggestive of myocardial ischemia or MI (Class I, Level of Evidence: A). ¹¹ 

Concluding remarks

Perioperative myocardial infarction is a major challenge requiring a comprehensive diagnostic Perioperative myocardial infarction is a major challenge requiring a comprehensive diagnostic and management approach. Including postoperative cardiac TnT measurements into the process of risk stratification after noncardiac surgery offers an important opportunity to decrease perioperative morbidity and mortality.³