P.J. Devereaux, MD, PhD; Denis Xavier, MD, MSc; Janice Pogue, MSc; Gordon Guyatt, MD, MSc; Alben Sigamani, MD; Ignacio Garutti, MD, PhD; Kate Leslie, MD, MEpi; Purnima Rao-Melacini, MSc; Sue Chrolavicius, RN; Homer Yang, MD; Colin MacDonald, MD; Alvaro Avezum, MD, PhD; Luc Lanthier, MD, MSc; Weijiang Hu, MD; Salim Yusuf, MBBS, DPhil; on behalf of the POISE (PeriOperative ISchemic Evaluation) Investigators
Grant Support: By the Canadian Institutes of Health Research, the Commonwealth Government of Australia's National Health and Medical Research Council, the Instituto de Salud Carlos III (PI071071, Ministerio de Sanidad y Consumo) in Spain, the British Heart Foundation, and AstraZeneca.
Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M10-2129.
Reproducible Research Statement:Study protocol: Available from Dr. Devereaux (e-mail, firstname.lastname@example.org). Statistical code and data set: Not available.
Requests for Single Reprints: P.J. Devereaux, MD, PhD, Population Health Research Institute, David Braley Cardiac, Vascular, and Stroke Research Institute, Room C1-116, Perioperative Medicine and Surgical Research Unit, Hamilton General Hospital, 237 Barton Street East, Hamilton, Ontario L8L 2X2, Canada; e-mail, email@example.com.
Current Author Addresses: Drs. Devereaux and Yusuf, Ms. Pogue, Ms. Rao-Melacini, and Ms. Chrolavicius: Population Health Research Institute, David Braley Cardiac, Vascular, and Stroke Research Institute, Room C1-116, Perioperative Medicine and Surgical Research Unit, Hamilton General Hospital, 237 Barton Street East, Hamilton, Ontario L8L 2X2, Canada.
Drs. Xavier and Sigamani: Division of Clinical Trials, St. John's Research Institute, Bangalore, Karnataka 560034, India.
Dr. Guyatt: 2C12, Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
Dr. Garutti: Department of Anesthesiology, Hospital General Gregorio Marañon, St/Doctor Esquerdo 46, Madrid 28009, Spain.
Dr. Leslie: Royal Melbourne Hospital, Department of Anaesthesia and Pain Management, Grattan Street, Parkville, Victoria 3050, Australia.
Dr. Yang: Department of Anesthesiology, The Ottawa Hospital, University of Ottawa, B309, 1053 Carling Avenue, Ottawa, Ontario K1Y 4E9, Canada.
Dr. MacDonald: 304 6203 28 Avenue, Edmonton, Alberta T6L 6K3, Canada.
Dr. Avezum: Dante Pazzanese Institute of Cardiology, São Paulo, 500 Av. Dante Pazzanese, São Paulo, Brazil 04012-909.
Dr. Lanthier: Centre Hospitalier Universitaire de Sherbrooke, 3001, 12e Avenue Nord, Sherbrooke, J1H 5N4 Québec, Canada.
Dr. Hu: Anshan Iron and Steel Mining Company Hospital Gongchangling, Anshan Liaoning, China 114021.
Author Contributions: Conception and design: J. Pogue, H. Yang.
Analysis and interpretation of the data: D. Xavier, J. Pogue, S. Chrolavicius, H. Yang, A. Avezum.
Drafting of the article: J. Pogue, A. Sigamani, H. Yang, A. Avezum.
Critical revision of the article for important intellectual content: D. Xavier, A. Sigamani, I. Garutti, K. Leslie, P. Rao-Melacini, H. Yang, A. Avezum, L. Lanthier.
Final approval of the article: P.J. Devereaux, D. Xavier, J. Pogue, G. Guyatt, I. Garutti, K. Leslie, S. Chrolavicius, H. Yang, C. MacDonald, A. Avezum, L. Lanthier.
Provision of study materials or patients: D. Xavier, I. Garutti, H. Yang, C. MacDonald, W. Hu.
Statistical expertise: J. Pogue, P. Rao-Melacini.
Obtaining of funding: K. Leslie, H. Yang.
Administrative, technical, or logistic support: D. Xavier, H. Yang.
Collection and assembly of data: D. Xavier, J. Pogue, A. Sigamani, I. Garutti, K. Leslie, S. Chrolavicius, H. Yang, L. Lanthier.
Devereaux P., Xavier D., Pogue J., Guyatt G., Sigamani A., Garutti I., Leslie K., Rao-Melacini P., Chrolavicius S., Yang H., MacDonald C., Avezum A., Lanthier L., Hu W., Yusuf S., ; Characteristics and Short-Term Prognosis of Perioperative Myocardial Infarction in Patients Undergoing Noncardiac Surgery: A Cohort Study. Ann Intern Med. 2011;154:523-528. doi: 10.7326/0003-4819-154-8-201104190-00003
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Published: Ann Intern Med. 2011;154(8):523-528.
Each year, millions of patients worldwide have a perioperative myocardial infarction (MI) after noncardiac surgery.
To examine the characteristics and short-term outcome of perioperative MI.
Cohort study. (ClinicalTrials.gov registration number: NCT00182039)
190 centers in 23 countries.
8351 patients included in the POISE (PeriOperative ISchemic Evaluation) trial.
Four cardiac biomarker or enzyme assays were measured within 3 days of surgery. The definition of perioperative MI included either autopsy findings of acute MI or an elevated level of a cardiac biomarker or enzyme and at least 1 of the following defining features: ischemic symptoms, development of pathologic Q waves, ischemic changes on electrocardiography, coronary artery intervention, or cardiac imaging evidence of MI.
Within 30 days of random assignment, 415 patients (5.0%) had a perioperative MI. Most MIs (74.1%) occurred within 48 hours of surgery; 65.3% of patients did not experience ischemic symptoms. The 30-day mortality rate was 11.6% (48 of 415 patients) among patients who had a perioperative MI and 2.2% (178 of 7936 patients) among those who did not (P < 0.001). Among patients with a perioperative MI, mortality rates were elevated and similar between those with (9.7%; adjusted odds ratio, 4.76 [95% CI, 2.68 to 8.43]) and without (12.5%; adjusted odds ratio, 4.00 [CI, 2.65 to 6.06]) ischemic symptoms.
Cardiac markers were measured only until day 3 after surgery, and additional asymptomatic MIs may have been missed.
Most patients with a perioperative MI will not experience ischemic symptoms. Data suggest that routine monitoring of troponin levels in at-risk patients is needed after surgery to detect most MIs, which have an equally poor prognosis regardless of whether they are symptomatic or asymptomatic.
Canadian Institutes of Health Research.
Darryl K Potyk
University of Washington School of Medicine
April 25, 2011
I read the recent article by Devereaux et al regarding perioperative myocardial infarctions (MI's) with interest. (1) Though the cohort data presented derives from a large prospective RCT, their findings are consistent with and confirm prior studies regarding perioperative myocardial ischemia and infarction. Namely that perioperative MI's are common, are often clinically silent and are associated with significant mortality.(2,3) A notable finding is that increased preoperative/baseline heart rate was an independent risk factor for perioperative MI. While the authors acknowledge this as a potentially modifiable risk factor, they refrain from commenting on their own prior findings that perioperative beta-blockade reduced cardiovascular deaths. The authors also refrain from commenting on the ensuing controversy regarding perioperative beta- blockade prescribed in a goal-directed fashion as opposed to the fixed- doses used in POISE trial. (3)
The authors' call for randomized controlled trials to investigate effective treatments for perioperative MI is appropriate. In the absence of such trials, however, their statement that "routine monitoring of cardiac biomarkers after surgery is essential" is premature and contrary to published ACC/AHA Perioperative Guidelines (4). The finding from the present study demonstrating that isolated biomarker elevation is more common than perioperative MI's should instead support the ACC/AHA guideline. Specifically, these findings confirm the reasoning behind the guideline: "On the basis of the available literature, routine measurement of cardiac specific troponin after surgery is more likely to identify patients without acute MI than with MI." (4)
Cardiac biomarker surveillance detects acute myocardial cell injury after it happens. Our efforts to decrease perioperative cardiac complications should be moved forward in time to facilitate intervention before cell injury/death results in a clinical event. Postoperative ST- segment depression has been shown to be a silent predecessor to clinical cardiac events.(2,3) Since ST-segment depression is present for 30 minutes prior to clinical events, early intervention based on ST-segment deviations hold greater potential to reduce perioperative cardiac morbidity and mortality than interventions instituted once damage has occurred. For these reasons, future RCT's directed at interventions based on ST-segment deviations should therefore be given higher priority than those utilizing cardiac biomarker surveillance.
Darryl Potyk, MD, FACP Clinical Professor of Medicine, University of Washington School of Medicine Internal Medicine Residency Spokane firstname.lastname@example.org
1) Devereaux PJ, Xavier D, Pogue J, et al. Characteristics and Short-Term Prognosis of Periperative Myocardial Infarction in Patients Undergoing Noncardiac Surgery. A Cohort Study. Annals of Internal Medicine. 2011;154:523-8.
2) Landesberg G, Luria MH, Cotev S, et al. Importance of long-duration postoperative ST-segment depression in cardiac morbidity after vascular surgery. Lancet 1993;341:715-9.
3) Mangano DT. Perioperative cardiac morbidity. Anesthesiology. 1990;72:153-184.
4) Devereaux PJ, Yang H, Yusuf S, et al. POISE Study Group. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE Trial): A randomized controlled trial. Lancet. 20058;371:1839-47.
5) Fleisher LA, Beckman JA, Brown KA, Calkins H, Chaikof E, Fleischmann KE, Freeman WK, Froehlich JB, Kasper EK, Kersten JR, Riegel B, Robb JF. ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery). J Am Coll Cardiol 2007;50:e159 -241.
July 14, 2011
Author's response. Need to Monitor Troponin Measurements after Noncardiac Surgery
Dr. Potyk states that we did not comment on the effects of perioperative beta-blockade. Based on all the beta-blocker trials in patients undergoing noncardiac surgery, there is strong evidence that beta -blockade prevents perioperative myocardial infarction. Contrary to Dr. Potyk's statement, perioperative beta-blockade likely increases the risk of death and almost certainly increases the risk of stroke.(1, 2) Our interpretation of these data is that in the perioperative setting there is a benefit to controlling the sympathetic system, but we need to find a way to do so safely and practically.
Dr. Potyk believes it is not necessary to monitor perioperative troponins in at-risk patients. We disagree for the following reasons: 1. our data suggests that 5.0% of at-risk patients will have a myocardial infarction and that 65.3% of these myocardial infarctions would have gone undetected without troponin monitoring; 2. patients suffering a perioperative myocardial infarction without ischemic symptoms have a poor prognosis (e.g., a 12.5% mortality rate at 30-days); 3. although 8.3% of patients had an isolated troponin elevation, these isolated troponin elevations represent myocardial injury and carry a poor prognosis (e.g., the highest quartile of these elevations was associated with a substantial increase [adjusted odds ratio, 2.54; 95% CI, 1.65-3.90] in 30-day mortality); 4. we have also recently demonstrated that troponin elevations after surgery independently impact (adjusted odds ratio 6.7; 95% CI, 4.1- 10.9) mortality until at least 12 months after surgery;(3)and 5. our data show that many patients with elevated troponin and perioperative myocardial infarction leave the hospital without medications that decrease the risk of major cardiovascular events (e.g. acetyl-salicylic acid, statins). Thus, awareness of elevated troponin and perioperative myocardial infarction is necessary for optimal informed decision-making in the post-operative period.
We agree that it is preferable to prevent a perioperative event than to treat an event. Continued efforts at evaluating a wide range of strategies are needed.
1. Devereaux PJ, Yang H, Yusuf S, Guyatt G, Leslie K, Villar JC, et al. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. Lancet. 2008;371(9627):1839-47.
2. Bangalore S, Wetterslev J, Pranesh S, Sawhney S, Gluud C, Messerli FH. Perioperative beta blockers in patients having non-cardiac surgery: a meta-analysis. Lancet. 2008;372(9654):1962-76.
3. Levy M, Heels-Ansdell D, Hiralal R, Bhandari M, Guyatt G, Yusuf S, et al. Prognostic value of troponin and creatine kinase muscle and brain isoenzyme measurement after noncardiac surgery: a systematic review and meta-analysis. Anesthesiology. 2011;114(4):796-806.
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