Correspondence Article Type Response to Letter Regarding Article, “Myocardial Injury After Noncardiac Surgery and Its Association With Short-Term Mortality” We thank Dr Xue and colleagues for their careful reading of our study1 on the association between postoperative myocardial injury and short-term mortality. In this study, we showed that postoperative myocardial injury, identified by routine troponin measurement monitoring, predicts short-term mortality after noncardiac surgery. By adjusting this association for preoperative variables known to predict mortality, we showed that myocardial injury was an independent predictor of mortality. In response to the important comments raised by Dr Xue et al, we point out the following. First, Dr Xue and colleagues state that the association reported may be confounded by other preoperative and intraoperative factors that were not adjusted for. We wish to underline that we aimed to determine the prognostic value of postoperative myocardial injury on the occurrence of short-term death to answer the question of whether patients at higher risk of death can be identified early after surgery by routine troponin measurements. Because a prognostic association by definition is not subject to confounding, the finding that myocardial injury predicts short-term death is valid without adjustment for other factors. Unfortunately, the question of whether postoperative myocardial injury also is causally related to death cannot be answered yet. To be able to investigate such a causal relationship, this association indeed must be adjusted for all possible confounding factors, including the factors suggested by Dr Xue and colleagues. Second, it is stated that initiating troponin measurements on the first postoperative day is not accurate to determine a cutoff value for the detection of myocardial injury because troponin elevations occur mostly during the first hours after myocardial ischemia. We agree that troponin elevations during the first hours after surgery may have been missed and that myocardial injury may have been found in even more patients if troponin had also been measured on the day of surgery. However, our aim was not to determine the ideal cutoff point of troponin to detect myocardial injury but to determine whether the association between myocardial injury and death was dependent on the level of troponin. Furthermore, the results from our study more closely reflect clinical practice because we used data from a clinical care protocol. Finally, we agree that including the causes of death and evaluating whether death could have been prevented would have added valuable information to our article. Unfortunately, because data on the cause of death were available for only a small proportion of patients (ie, the patients who died in the hospital), we considered these data not accurate enough to report. To solve the clinical problem of postoperative myocardial injury after noncardiac surgery, we believe that current research should focus on resolving its underlying pathophysiology and subsequently on evaluating whether treating patients with postoperative myocardial injury may improve their prognosis. If the pathophysiology is better understood and interventions are proven to be beneficial, then the timing of troponin measurement monitoring may be optimized to be able to treat patients as soon as required after surgery.

Acknowledgments This response is on behalf of the Cardiac Health After Surgery (CHASE) Investigators: University Medical Center Utrecht, the Netherlands, Department of Anesthesiology: Wolfgang F. Buhre, Jurgen C. de Graaff, Cor J. Kalkman, Wilton A. van Klei, Judith A.R. van Waes, Leo van Wolfswinkel; Department of Cardiology: Pieter A. Doevendans, Hendrik M. Nathoe, Remco B. Grobben; Department of Epidemiology: Diederik E. Grobbee, Linda M. Peelen; Department of Clinical Chemistry and Haematology: Hans Kemperman, Wouter W. van Solinge; Department of Radiology: Tim Leiner; Department of Surgery: Gert Jan de Borst, Loek P.H. Leenen, Frans L. Moll.

Disclosures None. Judith A.R. van Waes, MD Department of Anesthesiology University Medical Center Utrecht Utrecht, The Netherlands Hendrik M. Nathoe, MD, PhD Department of Cardiology University Medical Center Utrecht Utrecht, The Netherlands Jurgen C. de Graaff, MD, PhD Department of Anesthesiology University Medical Center Utrecht Utrecht, The Netherlands Hans Kemperman, PhD Department of Clinical Chemistry and Haematology University Medical Center Utrecht Utrecht, The Netherlands Gert Jan de Borst, MD, PhD Department of Surgery University Medical Center Utrecht Utrecht, The Netherlands Linda M. Peelen, PhD Department of Epidemiology University Medical Center Utrecht Utrecht, The Netherlands Wilton A. van Klei, MD, PhD Department of Anesthesiology University Medical Center Utrecht Utrecht, The Netherlands

References 1. van Waes JA, Nathoe HM, de Graaff JC, Kemperman H, de Borst GJ, Peelen LM, van Klei WA; Cardiac Health After Surgery (CHASE) Investigators. Myocardial injury after noncardiac surgery and its association with short-term mortality. Circulation. 2013;127:2264–2271.

(Circulation. 2014;129:e324.) © 2014 American Heart Association, Inc. Circulation is available at http://circ.ahajournals.org

DOI: 10.1161/CIRCULATIONAHA.113.007269

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Response to Letter Regarding Article, ''Myocardial Injury After Noncardiac Surgery and Its Association With Short-Term Mortality'' Judith A.R. van Waes, Hendrik M. Nathoe, Jurgen C. de Graaff, Hans Kemperman, Gert Jan de Borst, Linda M. Peelen and Wilton A. van Klei Circulation. 2014;129:e324 doi: 10.1161/CIRCULATIONAHA.113.007269 Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2014 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7322. Online ISSN: 1524-4539

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