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In Response

Sessler, Daniel I. MD; Devereaux, P. J. MD, PhD

doi: 10.1213/ANE.0000000000001820
Letters to the Editor: Letter to the Editor
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Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio, DS@OR.org

Population Health Research Institute and Departments of Clinical Epidemiology and Biostatistics and Medicine, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada

Funding: Supported by internal funds only. The authors have no personal financial interest related to this work.

A point we made in our article is that perioperative myocardial injury differs substantially from nonoperative myocardial infarctions.1 The distinction is critical. For example, Pal and Butterworth cite the 2012 American College of Cardiology guidelines that specify that acute coronary syndrome is unlikely in low-risk patients who have elevated troponin concentrations. However, the guidelines specifically refer to nonoperative patients.

We know from Vascular events In noncardiac Surgery patIents cOhort evaluation (VISION; n = 15,065) that postoperative myocardial infarctions are not restricted to high-risk patients.2 The only enrollment criterion for this international prospective cohort was inpatient surgery in patients who were at least 45 years old. Furthermore, participating hospitals deliberately enrolled a cross-section of patients making the results highly generalizable. In the VISION cohort, 10% of patients had elevated troponin concentrations after surgery, and 8% had centrally adjudicated myocardial infarctions based on clinical symptoms and/or consistent electrocardiographic or echocardiographic changes. It is thus obvious that risk is broadly distributed and that many postoperative infarctions will be missed if screening is restricted to patients with cardiovascular risk factors. In the VISION cohort, 8% of patients had elevated troponin concentrations after surgery of whom 42% fulfilled the universal definition of myocardial infarction based on an elevated troponin in the setting of clinical symptoms or electrocardiography or echocardiography ischemic changes.

Without troponin screening, 65% of the myocardial infarctions and 84% of the myocardial injuries after noncardiac surgery (MINS) go unrecognized.2 Approximately 80% of troponin increases are completely asymptomatic, which is in marked contrast to nonoperative myocardial infarctions that overwhelmingly present with chest pain and/or shortness of breath. Importantly, mortality is virtually identical in patients with symptomatic and asymptomatic troponin elevations. Asymptomatic postoperative troponin elevation is thus not just “troponitis”; instead, it indicates substantive myocardial injury that increases 30-day mortality by at least a factor of 10.3 The association between peak postoperative troponin and death is concentration-dependent with higher values predicting more deaths. For example, 30-day mortality is increased by an order of magnitude when troponin concentrations are between 0.03 and 0.29 ng/mL and 17-fold at even higher troponin concentrations.

Pal and Butterworth state “troponin is for diagnosis, not screening”; however, they subsequently suggest to screen perioperative troponin measurements in patients “with risk-factors for coronary disease undergoing operations that associate with increased risk of major adverse cardiac events.” The high frequency of myocardial injury supports our recommendation for postoperative troponin screening in most patients undergoing in-hospital noncardiac surgery who are ≥45 years of age.

The just published Canadian Cardiovascular Society (CCS) guidelines4 on perioperative cardiac risk assessment and management of patients having noncardiac surgery is slightly more conservative and gave a strong recommendation, based on moderate-quality evidence, for obtaining daily troponin measurements for 48 to 72 hours after noncardiac surgery in patients with a baseline risk >5% for cardiovascular death or nonfatal myocardial infarction at 30 days after surgery. That would include patients (1) with elevated NT-proBNP/BNP measurement before surgery; (2) a Revised Cardiac Risk Index score ≥1; (3) age 45 to 64 years with significant cardiovascular disease; or (4) age ≥65 years.

The CCS guidelines also address Pal and Butterworth’s question of whether a preoperative biomarker (they suggest troponin) might improve risk estimation and outcomes. Because the data are substantially stronger for NT-proBNP/BNP compared with that of troponin, the CCS guidelines give a strong recommendation, based on moderate-quality evidence, for obtaining a preoperative NT-proBNP/BNP measurement in patients with a baseline clinical risk estimate >5%.5

Pal and Butterworth state, “we find their recommendations for a medical or cardiology consultation equally unacceptable from those who regard themselves as perioperative physicians.” Patients who suffer MINS are at substantial increased risk for a recurrent major cardiac event, and observational data suggest that these patients benefit from basic secondary prophylactic measures including aspirin, statins, and angiotensin-converting enzyme inhibitors.6 Evidence also demonstrates that most documented postoperative myocardial injury patients are not even started on these basic medications.7

Patients suffering MINS need a physician who is comfortable initiating secondary prophylactic measures and is able to follow these patients in the outpatient setting. If anesthesiologists are able and willing to take on this role, we support their involvement, but if they are not, they should involve physicians who can provide patients with the care they need. Finally, an event with a 10% 30-day mortality certainly constitutes a “teachable moment” for lifestyle improvements, including smoking cessation, exercise, and a healthful diet. Such interventions seem most likely to prove effective when accompanied by a degree of follow-up that few anesthesiologists can offer.

Pal and Butterworth question whether the cost of troponin screening is justified. Fortunately, the test is inexpensive and available worldwide. Compared with so many low-value perioperative tests, troponin has a number needed to test of just 15 for a condition with a 10% 30-day mortality. That the cost is justified thus seems obvious, a conclusion supported by formal analysis.8 In contrast, many common preoperative risk assessment tests such as stress echocardiograms are expensive and provide little prognostic value.9

In summary, postoperative myocardial injury is rarely accompanied by symptoms, meaning that approximately 80% of cases will be missed without troponin screening (the number needed to test is only approximately 15 patients). Mortality is 10% at 30 days, making myocardial injury a leading cause of short-term postoperative death, and mortality is nearly identical with and without symptoms. Asymptomatic troponin elevate is thus highly prognostic and screening is cost-effective. Fourth-generation troponin T concentrations ≥0.03 ng/mL should prompt a cardiology consult and interventions that might include aspirin, angiotensin-converting enzyme inhibitors, and statins; blood pressure and heart rate control; and lifestyle enhancements including smoking cessation, exercise, and a healthful diet.

Daniel I. Sessler, MDDepartment of Outcomes ResearchAnesthesiology InstituteCleveland ClinicCleveland, OhioDS@OR.org

P. J. Devereaux, MD, PhDPopulation Health Research Institute and Departments ofClinical Epidemiology and Biostatistics and MedicineHamilton Health Sciences and McMaster UniversityHamilton, Ontario, Canada

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REFERENCES

1. Sessler DI, Devereaux PJ. Perioperative troponin screening. Anesth Analg. 2016;123:359–360.
2. The Vascular events In noncardiac Surgery patIents cOhort evaluatioN (VISION) Investigators: myocardial injury after noncardiac surgery—a large, international, prospective cohort study establishing diagnostic criteria, characteristics, predictors, and 30-day outcomes. Anesthesiology. 2014;120:564–578.
3. The Vascular Events In Noncardiac Surgery Patients Cohort Evaluation (VISION) Study Investigators. Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery. JAMA. 2012;307:2295–2304.
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7. Foucrier A, Rodseth R, Aissaoui M, et al. The long-term impact of early cardiovascular therapy intensification for postoperative troponin elevation after major vascular surgery. Anesth Analg. 2014;119:1053–1063.
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9. Devereaux PJ, Sessler DI. Cardiac complications in patients undergoing major noncardiac surgery. N Engl J Med. 2015;373:2258–2269.
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