Peripheral arterial occlusive disease and perioperative risk

This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use i not permitted. It is not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, log or other proprietary information of the Publisher. © COPYRIGHT 2018 EDIZIONI MINERVA MEDICA © 2018 eDIZIoNI MINerVa MeDICa online version at http://www.minervamedica.it International angiology 2018 april;37(2):93-9 DoI: 10.23736/S0392-9590.18.03897-X REVIEW Peripheral arterial occlusive disease and perioperative risk Peter PoreDoS 1 *, Pavel PoreDoS 2 1Department of anesthesiology and Perioperative Intensive Care, University Medical Center ljubljana, ljubljana, Slovenia; 2Department of Vascular Disease, University Medical Center ljubljana, ljubljana, Slovenia *Corresponding author: Peter Poredos, Department of anesthesiology and Perioperative Intensive Care, University Medical Center ljubljana, Zaloska 7, SI-1000 ljubljana, Slovenia. e-mail: peter.poredos@kclj.si aBStraCt Surgical procedures represent a risk for different complications which may appear during the perioperative period. Cardiac ischemic events and vascular complications are the most important causes of increased morbidity and mortality and they are much more frequent in patients with manifest cardiovascular disease. this is particularly seen in patients with peripheral arterial occlusive disease (PaD), which represents advanced atherosclerosis frequently accompanied by the presence of coronary artery disease. therefore, patients with PaD need careful preoperative examination, including estimation of functional capacity and the presence of other co-existing atherosclerotic diseases. the perioperative risk of cardiac complications should be calculated by apgar score. In patients with unstable coronary syndrome myocardial revascularization should be performed before vascular procedures, whereas in other coronary patients pharmacotherapy should be intensified. The latter includes beta-adrenergic receptor blockers, statin therapy, which significantly improves postoperative outcome and antiplatelet drugs, which do not significantly increase major bleeding complications but significantly reduce cardiovascular thromboembolic events. Postoperative strategy for prevention of complications should be focused particularly on identification of myocardial infarction which is frequently asymptomatic. Therefore, serial postoperative measurements of troponin levels allow close monitoring of postoperative myocardial damage and help to implement strategic choices for the treatment of postoperative adverse cardiac events. (Cite this article as: Poredos P, Poredos P. Peripheral arterial occlusive disease and perioperative risk. Int angiol 2018;37:93-9. DoI: 10.23736/ S0392-9590.18.03897-X) Key words: Myocardial ischemia - Preoperative care - Intraoperative complications - risk management - Postoperative care. S urgical procedures represent a stress to a body and may also produce different complications: hemorrhage — either during surgery or in the postoperative period, dehydration, pneumonia, deep venous thrombosis, post-operative wound infection, pulmonary embolism and sepsis. However, the most frequent complications are cardiovascular events particularly myocardial infarction and arrhythmias. the incidence of cardiovascular events is higher in patients with simultaneous clinical manifestations of atherosclerotic disease in different vascular beds.1 Peripheral arterial atherosclerotic disease of lower limbs (PaD) represents one of the most frequent manifestations of atherosclerosis and is associated with the highest risk of concomitant atherosclerotic lesions in other Vol. 37 - No. 2 vascular territories.2 therefore, subjects with PaD are likely to have simultaneous preclinical or clinical atherosclerotic lesions of coronary and/or cerebrovascular vascular bed, which increases the risk of perioperative morbidity and mortality.3 the risk of perioperative complications depends not only on the presence of comorbidities but also on the condition of a patient prior to surgery and the magnitude and duration of a surgical procedure.4 Cardiac complications, which represent a leading cause of perioperative morbidity and mortality, can appear in patients with ischemic heart disease, left-ventricular dysfunction and valvular heart disease; besides this they are more common in patients who undergo procedures that are associated with prolonged hemodynamic and cardiac INterNatIoNal aNgIology 93 This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use i not permitted. It is not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, log or other proprietary information of the Publisher. © COPYRIGHT 2018 EDIZIONI MINERVA MEDICA PoreDoS PaoD aND PerIoPeratIVe rISK stress. Different guidelines dealing with perioperative risk of cardiovascular complications during cardiac and non-cardiac surgery exist,5, 6 but these documents are general and not specifically dedicated to patients with PAD. This review summarizes the latest findings on perioperative cardiovascular risk in patients with PaD and current practice for reduction of risk related to surgical procedure. PAD as an indicator of a high risk for perioperative complications Different studies have shown that PaD is frequently accompanied by the presence of CHD in up to 42% of patients and that these patients have an impaired cardiac function.2 Bolognesi et al. demonstrated that in PaD patients assigned to surgical revascularization there is a high percentage of smokers, subjects with metabolic disorders, renal failure, atrial arrhythmias and previous myocardial infarction as well as left ventricular dysfunction.7 therefore, in PaD patients, perioperative mortality and morbidity predominantly depends on the presence of coronary heart disease (CHD) which is responsible for at least 40% of deaths.8 Not only the presence of cardiac disease, but also the involvement of other vascular territories by atherosclerosis influences perioperative complications and mortality in PaD patients. It has been shown that in patients with two or more atherosclerotic diseases the perioperative risk is 2-3 times higher than in patients with only one atherosclerotic disease.9 Besides the spread of atherosclerotic process, perioperative complications depend also on the management of risk factors of atherosclerosis. It has been shown that in comparison to CHD patients, risk factors of atherosclerosis in PaD patients are undertreated. only 36% of PaD patients are treated with antiplatelets, 30% with statins and 25% with angiotensin converting enzyme inhibitors.10, 11 Determination of perioperative risk every surgical procedure provokes a stress response. this response is initiated by tissue injury and mediated by neuroendocrine factors that may induce tachycardia and hypertension increasing myocardial oxygen demand. Surgery also causes alteration in the balance 94 between prothrombotic and fibrinolytic factors, resulting in hypercoagulability and possible coronary thrombosis. all these factors may cause cardiac ischemia and heart failure. With regards to cardiac risk, surgical procedures can be divided into: low-risk, intermediate risk and highrisk groups with estimated 30-day cardiac event rates of 1, 1-5, and >5%, respectively (table I).12 Risk stratification provides a useful tool to identify the need for preoperative cardiac evaluation, drug treatment and assessment of risk for cardiac events. the need for and value of preoperative cardiac evaluation will also depend on the urgency of surgery. In case of emergency such as ruptured abdominal aortic aneurysm, cardiac evaluation will not change the course and results of the surgical procedure.5 However, in less urgent surgical conditions, such as by-pass surgery in patients with acute limb ischemia, cardiological evaluation may influence the surgical procedure with the choice of less invasive interventions. In some cases, cardiac evaluation can reliably predict perioperative cardiac complications and influence the decision whether to perform a procedure or not (e.g. small abdominal aortic aneurysm or asymptomatic carotid stenosis).13 In vascular surgical procedures, specific preoperative investigations are essential because of the highest risk of cardiac complications. open aortic and infra-inguinal procedures are both to be considered as such procedures.12 The choice of specific diagnostic procedures depends on the grade of risk which is estimated from the history and clinical examination. a very important indicator of perioperative risk is the functional status of the patient. Table I.—Surgical risk of myocardial infarction and cardiac death within 30 days.12 low risk (<1%) – – – – – – – Breast Dental endocrine eye gynecology reconstructive orthopedic-minor (knee surgery) – Urologic-minor INterNatIoNal aNgIology Intermediate risk (1-5%) – abdominal – Carotid – Peripheral arterial angioplasty – endovascular aneurysm repair – Head and neck surgery – Neurological/ orthopedic-major (hip and spine surgery) – Pulmonary renal – Urologic-major High risk (>5%) – aortic surgery – Major peripheral vascular surgery april 2018 This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use i not permitted. It is not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, log or other proprietary information of the Publisher. © COPYRIGHT 2018 EDIZIONI MINERVA MEDICA PaoD aND PerIoPeratIVe rISK PoreDoS In patients with reduced functional capacity determined by metabolic equivalents (<4 Mets) additional diagnostic work-up is necessary.5 exercise testing provides an objective assessment of functional capacity. the inability to climb two flights of stairs or run a short distance (<4 Mets) also indicates low functional capacity and is associated with an increased incidence of postoperative cardiac events. When functional capacity is high, the prognosis is excellent, even in the presence of stable ischemic heart disease.14 Different scoring systems exist for the estimation of the risk of perioperative cardiac complications. one of the most frequently used scoring systems is the revised Cardiac risk Index (rCrI), which includes ischemic heart disease, heart failure, cerebrovascular disease, creatinine levels (>2 mg/dL or >170 μmol/L) and diabetes mellitus. Based on the presence of the mentioned risk factors patients are categorized in four classes (I-IV). Using this score the risk of perioperative complications is estimated at 0.4% in patients without any risk factors and it increases up to 11.0% in patients with three or more risk factors. Patients in categories III-IV need further preoperative investigations of the cardiovascular system.15, 16 Some validation studies have suggested that this index is probably sub-optimal for identifying patients with multiple risk factors and its weakness is also that the type of surgery is only classified into 2 subtypes.12 There are also other classifications, such as the Erasmus model. In this model an exact description of the type of surgery and age are included which increase the prognostic value of the model for perioperative cardiac events.12 In addition to the above-mentioned scoring systems, biomarkers are indicators of pathologic processes during and after surgery. Some of them are focusing on myocardial ischemia (cardiac troponin t1), others on inflammation (C-reactive protein). In recent years interest has focused on the potential role of other cardiac biomarkers in the perioperative cardiac risk assessment. especially, B-type natriuretic peptide (BNP) and N-terminal pro-BNP have deserved attention in this respect. recent data suggest that preoperative levels of these biomarkers may also have prognostic value for mortality and cardiac events after non-cardiac surgery.17 However, the data on the prognostic value of biomarkers is sparse.18 Vol. 37 - No. 2 Table II.—Recommendations on stress testing prior to surgery.30 recommendations Class level Stress testing is recommended in high-risk surgery patients I with ≥2 clinical factors Stress testing may be considered in high-risk surgery IIb patients with ≤2 clinical factors Stress testing may be considered in intermediate-risk surgery IIb Stress testing is not recommended in low-risk surgery III C B C C In patients with a moderate or a high risk for perioperative cardiovascular complications the following investigations are recommended: 12-channel eCg and echocardiography, indicated in symptomatic patients or in patients with cardiac murmurs. For myocardial ischemia detection, exercise eCg and non-invasive imaging techniques represent basic investigations. High-risk surgical patients should undergo dobutamine and stress echocardiography or nuclear stress testing. the prognostic value of the extent of ischemic myocardium, using semi-quantitative dipyridamole myocardial perfusion imaging, has been investigated in meta-analysis of studies in vascular surgery patients.5 It was shown that reversible ischemia involving <20% of the left ventricular myocardium did not change the rate of perioperative cardiac events. However, patients with more extensive irreversible defects were at increased risk. recommendations on stress-testing prior to surgery and levels of evidence are presented in table II. Intraoperative risk stratification Until recently there was a lack of possibilities to routinely and reliably assess the patient’s condition at the end of the operation. gawande et al. introduced the apgar score for surgery, a 10-point score, which is based on the patient’s estimated amount of blood loss, lowest heart rate and lowest mean arterial pressure, factors which are significantly associated with major complications or death within 30 days after surgery.19 there have been suggestions that the apgar score for surgery should be used to objectively guide postoperative care and may make a difference in postoperative care.20 However, further studies are needed. Detection of perioperative myocardial ischemia Myocardial injury after non-cardiac surgery is associated with an increase in both short-term and long-term INterNatIoNal aNgIology 95 This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use i not permitted. It is not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, log or other proprietary information of the Publisher. © COPYRIGHT 2018 EDIZIONI MINERVA MEDICA PoreDoS PaoD aND PerIoPeratIVe rISK mortality and is one of the main complications in patients with PaD, particularly in the postoperative period.21 the clinical picture of postoperative myocardial infarction (PMI) seems to be quite variable. In about 8% of PMI cases no chest-pain or any other typical symptoms are present. also, electrocardiographic changes are present only in about 35% of patients with PMI. Nevertheless, mortality of patients with PMI is substantial and accounts between 9.8% and 12.6%. the most sensitive marker of myocardial injury is a cardiac-selective troponin.22 therefore, the current american Heart association / american College of Cardiology guidelines for the perioperative cardiovascular evaluation and care of the cardiac patient of non-cardiac surgery recommend postoperative troponin surveillance in patients with eCg changes or typical ischemic pain and a weak recommendation for troponin surveillance is given for clinically stable patients who undergo vascular or intermediate-risk surgery.23 recent studies also suggest that perioperative cardiac troponin release is common and strongly associated with mortality.24 Perioperative pain, inflammatory reaction and increased sympathetic tone increase myocardial oxygen demand and decrease myocardial oxygen supply, which particularly appears in patients with significant as well as in non-significant coronary stenosis.25 therefore, not only symptomatic, but also asymptomatic troponin leak in the perioperative period is diagnostically and clinically important. How to reduce perioperative mortality in patients who undergo non-cardiac vascular surgery? Because the presence of coronary artery disease and insufficient pharmacotherapy represent the most important factors associated with increased perioperative mortality of PaD patients, in each patient, particularly those at high risk, the need for coronary revascularization should be assessed and pharmacotherapy should be optimized. In patients with unstable coronary syndrome, coronary revascularization should be performed before peripheral vascular procedures. In patients with stable angina pectoris, coronary revascularization does not affect outcome, including mortality,5 apart from the patients with left main stem coronary artery disease. the latter experience improvement in survival with preoperative coronary revascularization.26 Appropriate pharmacotherapy significantly improves 96 perioperative outcome. Continuation or introduction of the drugs listed below, particularly β1-adrenergic receptor blockers, reduces perioperative morbidity and mortality. Beta-blockers have the ability to modulate the perioperative stress response and despite the lack of unequivocal evidence,27 previous guidelines have supported preoperative initiation of these drugs to minimize the risk of perioperative complications. recently, these recommendations have been challenged although evidence is growing that the protective effect of perioperative β-blocking therapy may prevent the deleterious effects of intraoperative stress and anemia on postoperative outcome.28 Conversely, trials including low-risk patients suggest that perioperative β-blockers do not decrease the risk of cardiac complication in patients without clinical risk factors.29 Beta-blockers should not be withdrawn in patients on continuous treatment with these drugs, including patients with stable heart failure. In decompensated heart failure, β-blockers therapy may need to be reduced or temporarily omitted.30 recent studies also show that cardio-protective β-blockers are associated with reduced mortality in patients with chronic obstructive pulmonary disease undergoing vascular surgery.31 The dosage of β-blockers should be titrated to achieve a heart rate between 60-70 beats/min. β1 selective blockers without intrinsic sympathomimetic activities are favored. alpha-2 antagonists have the potential to modulate perioperative sympathetic stimulation and outcome.5 However, recent results of the Perioperative Ischemic Evaluation (POISE) 2 study indicated that α2antagonists had no effect on the incidence of PMI and mortality, but were associated with higher incidence of intraoperative hypotension and non-fatal cardiac arrest.32 lipid lowering has been proven to be highly effective in the secondary prevention of atherosclerosis. there is also increasing evidence that perioperative statin therapy improves postoperative outcome. Meta-analyses evaluating the effect of preoperative statin therapy on postoperative outcome have shown that it reduces the mortality after vascular surgery by 59% 33 and statin withdrawal for more than 4 days in the perioperative period is associated with a 3-fold increased risk of postoperative myocardial ischemia.34 Statins have not only lipid-lowering effect but also INterNatIoNal aNgIology april 2018 This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use i not permitted. It is not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, log or other proprietary information of the Publisher. © COPYRIGHT 2018 EDIZIONI MINERVA MEDICA PaoD aND PerIoPeratIVe rISK PoreDoS induce coronary plaque stabilization by decreasing lipid oxidation and inflammation. These effects may prevent plaque rupture and subsequent myocardial infarction in the perioperative period.35 therefore, for patients undergoing vascular surgery with or without clinical risk factors, statin use is advisable. Statins should be introduced at least one week before the operation. Because of lack of an intravenous formulation, statins with long half-life or extended release such as rosuvastatin, atorvastatin and fluvastatin are recommended to bridge the period immediately after surgery when oral intake is not feasible. Perioperative statin therapy is related to higher risk of statin-induced myopathy and rhabdomyolysis, which could be induced by anesthesia, impairment of renal function and the type of surgery.36 However, benefit of preoperative statin treatment is much higher than the risk of their harmful side-effects. angiotensin-converting enzyme (aCe) inhibitors besides having blood pressure lowering effect to preserve organ function they also improve endothelial function and have an anti-inflammatory effect.37 therefore, treatment with ACE inhibitors may have beneficial effects on postoperative outcome. In the QUo VaDIS study, it was shown that quinapril reduces cardiovascular events in patients undergoing cardiac surgery.38 However, review of trials with ACE inhibitors provided conflicting data concerning efficacy of these drugs after cardiac surgery. Perioperative use of aCe inhibitors caries a risk of severe hypotension under anesthesia.39 treatment with antiplatelet drugs may prevent major cardiovascular complications in the perioperative period.40 on the other hand, the overview of the literature shows that in most surgical procedures including peripheral arterial vascular procedures low dose aspirin may result in increased frequency of procedural bleeding, but not in an increase in severity of bleeding complications or perioperative mortality.41 the Perioperative Ischemic evaluation 2 (PoISe-2) trial suggests that aspirin administration during the perioperative period does not change the risk of a cardiovascular event and may result in increased bleeding.42 thus, when used for primary prevention, antiplatelets may be safely discontinued perioperatively. However, in patients with PaD receiving aspirin for secondary prevention undergoing general surgery, orthopedic surgery, ophthalmological surgery, cardiovascular surgery, major vascular surgery, or a urological procedure, continuation of aspirin Vol. 37 - No. 2 is probably useful, but further study is required. therefore, decisions regarding the perioperative continuation of aspirin should be made on a case-by-case risk-benefit analysis. Postoperative strategies for prevention of perioperative complications In 2012, Pearse, et al. reported the results of a large prospective analysis of in-hospital mortality of surgical patients enrolled from 28 european countries.43 the most important finding of this study was an overall mortality of 4% with a huge variability from 1.2 for Iceland to 21.5 for latvia. the authors concluded that this huge difference in mortality was related to a failure of the system to recognize and promptly treat adverse events in early postoperative period, such as: hypotension, anemia and hypoxia, which often remain undetected.44 Most postoperative complications (PMIs) occur within the first 48-hours after non-cardiac surgery. As these patients usually receive analgesics, most them do not experience pain as the most recognizable symptom of myocardial ischemia. therefore, it is obvious that postoperative monitoring of troponin levels can have a key role in diagnosis of perioperative myocardial ischemic events and may provide a better prediction of cardiac outcomes than preoperative risk-assessment.45 It seems that postoperative troponin level is perhaps not only a marker of perioperative myocardial damage, but more generally a marker of perioperative hazard.46 therefore, it seems that close monitoring of this biomarker may have a role in the risk stratification for postoperative adverse events and help in identifying patients who need careful monitoring and specific preventive measures. Postoperative eCg changes may be associated with postoperative mortality, they should occur concomitantly with the troponin leak and only then certain specific ECG changes are potentially independently predictive of mortality. Further, in patients who are troponin positive, eCg changes are more common in those with greater troponin leak.47 as it was shown in the VISIoN (Vascular events in Non-Cardiac Surgery Patients Cohort evaluation) study the following postoperative eCg changes were independently associated with 30-day mortality in the presence of troponin elevation: St-elevation, left bundle branch block and anterior wall ischemic eCg changes.48 INterNatIoNal aNgIology 97 This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use i not permitted. It is not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, log or other proprietary information of the Publisher. © COPYRIGHT 2018 EDIZIONI MINERVA MEDICA PoreDoS PaoD aND PerIoPeratIVe rISK The question is, whether intensification of therapy in patients with elevated biomarkers indeed improves the outcome. Some data indicate that the use of antiplatelet drugs, β-blockers, statins and ACE-inhibitors in patients who develop elevated postoperative troponin levels are associated with an improvement in outcome.49 However, this is not generally accepted. 8. Conclusions PaD patients are at highest risk of cardiovascular complications including perioperative morbidity and mortality. High perioperative morbidity is a consequence of advanced atherosclerosis in PaD patients and undertreatment of risk factors for atherosclerosis. Preoperatively PaD patients should be carefully examined and investigated for the presence and extent of atherosclerotic diseases and pharmacotherapy should be optimized. Patients should also be carefully followed postoperatively. Because of frequent appearance of cardiac ischemia monitoring of troponin levels is indicated. 9. 10. 11. 12. 13. References 1. 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Vasc Health risk Manag 2010;6:287-96. De Hert S, Moerman a, De Baerdemaeker l. Postoperative complications in cardiac patients undergoing noncardiac surgery. Curr opin Crit Care 2016;22:357-64. INterNatIoNal aNgIology april 2018 This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use i not permitted. It is not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, log or other proprietary information of the Publisher. © COPYRIGHT 2018 EDIZIONI MINERVA MEDICA PaoD aND PerIoPeratIVe rISK PoreDoS 23. 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Myocardial injury after noncardiac surgery: a large, international, prospective cohort study establishing diagnostic criteria, characteristics, predictors, and 30-day outcomes. anesthesiology 2014;120:564-78. 49. Foucrier a, rodseth r, aissaoui M, Ibanes C, goarin JP, landais P, et al. The long-term impact of early cardiovascular therapy intensification for postoperative troponin elevation after major vascular surgery. anesth analg 2014;119:1053-63. Conflicts of interest.—The authors certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript. Article first published online: January 11, 2018. - Manuscript accepted: January 3, 2018. - Manuscript revised: December 20, 2017. - Manuscript received: July 30, 2017. Vol. 37 - No. 2 INterNatIoNal aNgIology 99