Troponin elevation after noncardiac surgery: Significance and management
ABSTRACTHow to interpret and manage troponin elevations after noncardiac surgery is a common clinical question for cardiologists and internists. An estimated 5% to 25% of patients who undergo noncardiac surgery have an elevated postoperative troponin level. Patients with troponin elevation are at higher short-term and long-term risk of morbidity and mortality. Current guidelines provide few recommendations on how to manage these patients. The authors review the evidence and guidelines and propose treatment strategies.
KEY POINTS
- Cardiovascular events are a major cause of morbidity and mortality in patients undergoing noncardiac surgery and occur frequently, especially in high-risk patients.
- Myocardial injury or infarction after noncardiac surgery heightens the short- and long-term risk of mortality and major adverse cardiac events.
- The dominant mechanism of myocardial injury after noncardiac surgery remains uncertain.
- In the absence of therapies proven to affect the outcome, the benefit of screening to identify these patients remains uncertain.
- Clinical trials are under way to help clinicians provide optimal care to this at-risk population.
POSTOPERATIVE TROPONIN ELEVATION CARRIES A WORSE PROGNOSIS
Patients who suffer a myocardial infarction after noncardiac surgery have worse short- and long-term outcomes than their counterparts.4,5,7, 8,10,33 In the POISE trial,10 the 30-day mortality rate was 11.6% in those who had had a perioperative myocardial infarction, compared with 2.2% in those who did not (P < .001). The patients who had had a myocardial infarction were also more likely to have nonfatal cardiac arrest, coronary revascularization, and congestive heart failure.
Myocardial injury not fulfilling the criteria for myocardial infarction after noncardiac surgery is also associated with worse short-term and long-term outcomes.3,6,10,11,37,38 POISE patients with isolated elevations in cardiac biomarkers had a higher 30-day risk of coronary revascularization and nonfatal arrest.10 In the VISION trial, an elevation in troponin was the strongest predictor of death within 30 days after noncardiac surgery. This analysis also showed that the higher the peak troponin value, the greater the risk of death and the shorter the median time until death.11
A meta-analysis of 14 studies in 3,139 patients found that elevated troponin after noncardiac surgery was an independent predictor of death within 1 year (odds ratio [OR] 6.7, 95% confidence interval [CI] 4.1–10.9) and beyond 1 year (OR 1.8, 95% CI 1.4–2.3).37
SHOULD SCREENING BE ROUTINE AFTER NONCARDIAC SURGERY?
Since patients suffering myocardial infarction or injury after noncardiac surgery have a worse prognosis, many experts advocate routinely screening all high-risk patients and those undergoing moderate- to high-risk surgery. Many tools exist to determine which patients undergoing noncardiac surgery are at high risk of cardiac complications.
The revised Goldman Cardiac Risk Index is commonly used and well validated. Variables in this index that predict major cardiac complications are:
- High-risk surgery (vascular surgery, orthopedic surgery, and intraperitoneal or intrathoracic surgery)
- History of ischemic heart disease
- History of congestive heart failure
- History of cerebrovascular disease
- Diabetes requiring insulin therapy
- Chronic kidney disease with a creatinine > 2.0 mg/dL.
The more of these variables that are present, the higher the risk of perioperative cardiac events2,4:
- No risk factors: 0.4% risk (95% CI 0.1–0.8)
- One risk factor: 1.0% risk (95% CI 0.5–1.4)
- Two risk factors: 2.4% risk (95% CI 1.3–3.5)
- Three or more risk factors: 5.4% risk (95% CI 2.7–7.9).
Current guidelines from the American College of Cardiology and the American Heart Association give a class I recommendation (the highest) for measuring troponin levels after noncardiac surgery in patients who have symptoms or signs suggesting myocardial ischemia. They give a class IIb recommendation (usefulness is less well established) for screening those at high risk but without symptoms or signs of ischemia, despite the previously cited evidence that patients with troponin elevation are at increased risk. The IIb recommendation is due to a lack of validated treatment strategies to modify and attenuate the recognized risk with troponin elevation in this setting.39
LITTLE EVIDENCE TO GUIDE TREATMENT
In current practice, internists and cardiologists are often asked to consult on patients with troponin elevations noted after noncardiac surgery. Although published and ongoing studies examine strategies to prevent cardiovascular events during noncardiac surgery, we lack data on managing the cases of myocardial infarction and injury that actually occur after noncardiac surgery.
When managing a patient who has a troponin elevation after surgery, many clinical factors must be weighed, including hemodynamic and clinical stability and risk of bleeding. Confronted with ST-segment elevation myocardial infarction or high-risk non–ST-segment elevation myocardial infarction, most clinicians would favor an early invasive reperfusion strategy in accordance with guidelines on managing acute coronary syndrome. Fibrinolytic drugs for ST-segment elevation myocardial infarction are likely to be contraindicated in the postoperative period because they pose an unacceptable risk of bleeding.
Guideline-directed medical therapies for those suffering perioperative myocardial infarction may lower the risk of future cardiovascular events, as suggested by a retrospective study of 66 patients diagnosed with perioperative myocardial infarction after vascular surgery.40 Those in whom medical therapy for coronary artery disease was not intensified—defined as adding or increasing the dose of antiplatelet agent, statin, beta-blocker, or angiotensin-converting enzyme inhibitor—had higher rates of cardiovascular events at 12 months (hazard ratio [HR] 2.80, 95% CI 1.05–24.2).40
In those with asymptomatic myocardial infarction or isolated elevation in cardiac biomarkers, no treatment strategies have been assessed prospectively or in randomized trials. However, statins and aspirin have been suggested as providing some benefit. In a substudy of the POISE trial, the use of aspirin was associated with a 46% reduction in the 30-day mortality rate in those suffering a perioperative myocardial infarction, and statins were associated with a 76% reduction.10 In a single-center retrospective analysis of 337 patients undergoing moderate- to high-risk vascular surgery, statin therapy was associated with a lower 1-year mortality rate (OR 0.63, 95% CI 0.40–0.98).38
We propose a treatment algorithm for patients identified as having cardiovascular events after noncardiac surgery (Figure 2), based on current evidence and guidelines. Ultimately, treatment decisions should be tailored to the individual patient. Discussion of the risks and benefits of therapeutic options should include the patient and surgeon.
Ongoing and future trials
Ongoing and future trials are aimed at addressing definitive treatment strategies in this patient population.
The MANAGE trial (Management of Myocardial Injury After Non-cardiac Surgery Trial) is randomizing patients suffering myocardial injury after noncardiac surgery to receive either dabigatran and omeprazole or placebo to assess the efficacy of these agents in preventing major adverse cardiac events and the safety of anticoagulation (ClinicalTrials.gov Identifier: NCT01661101).
The INTREPID trial (Study of Ticagrelor Versus Aspirin Treatment in Patients With Myocardial Injury Post Major Non-Cardiac Surgery) will assess the efficacy and safety of ticagrelor treatment compared with aspirin in a similar population (ClinicalTrial.gov Identifier: NCT02291419). The trial will enroll approximately 1,000 patients identified as having a postoperative troponin elevation more than two times the upper limit of normal of the assay during the index hospitalization (Figure 3). Enrollment was to have begun in mid-2015.
