Myocardial Injury After Noncardiac Surgery

Myocardial injury after non-cardiac surgery (MINS) increases the risk of cardiovascular events and deaths, which anticoagulation therapy could prevent. Dabigatran prevents perioperative venous thromboembolism, but whether this drug can prevent a broader range of vascular complications in patients with MINS is unknown. The MANAGE trial assessed the potential of dabigatran to prevent major vascular complications among such patients. In this international, randomised, placebo-controlled trial, we recruited patients from 84 hospitals in 19 countries. Eligible patients were aged at least 45 years, had undergone non-cardiac surgery, and were within 35 days of MINS. Patients were randomly assigned (1:1) to receive dabigatran 110 mg orally twice daily or matched placebo for a maximum of 2 years or until termination of the trial and, using a partial 2-by-2 factorial design, patients not taking a proton-pump inhibitor were also randomly assigned (1:1) to omeprazole 20 mg once daily, for which results will be reported elsewhere, or matched placebo to measure its effect on major upper gastrointestinal complications. Research personnel randomised patients through a central 24 h computerised randomisation system using block randomisation, stratified by centre. Patients, health-care providers, data collectors, and outcome adjudicators were masked to treatment allocation. The primary efficacy outcome was the occurrence of a major vascular complication, a composite of vascular mortality and non-fatal myocardial infarction, non-haemorrhagic stroke, peripheral arterial thrombosis, amputation, and symptomatic venous thromboembolism. The primary safety outcome was a composite of life-threatening, major, and critical organ bleeding. Analyses were done according to the intention-to-treat principle. This trial is registered with ClinicalTrials.gov, number NCT01661101. Between Jan 10, 2013, and July 17, 2017, we randomly assigned 1754 patients to receive dabigatran (n=877) or placebo (n=877); 556 patients were also randomised in the omeprazole partial factorial component. Study drug was permanently discontinued in 401 (46%) of 877 patients allocated to dabigatran and 380 (43%) of 877 patients allocated to placebo. The composite primary efficacy outcome occurred in fewer patients randomised to dabigatran than placebo (97 [11%] of 877 patients assigned to dabigatran vs 133 [15%] of 877 patients assigned to placebo; hazard ratio [HR] 0·72, 95% CI 0·55-0·93; p=0·0115). The primary safety composite outcome occurred in 29 patients (3%) randomised to dabigatran and 31 patients (4%) randomised to placebo (HR 0·92, 95% CI 0·55-1·53; p=0·76). Among patients who had MINS, dabigatran 110 mg twice daily lowered the risk of major vascular complications, with no significant increase in major bleeding. Patients with MINS have a poor prognosis; dabigatran 110 mg twice daily has the potential to help many of the 8 million adults globally who have MINS to reduce their risk of a major vascular complication [corrected]. Boehringer Ingelheim and Canadian Institutes of Health Research.

Little is known about the relationship between perioperative high-sensitivity troponin T (hsTnT) measurements and 30-day mortality and myocardial injury after noncardiac surgery (MINS). To determine the association between perioperative hsTnT measurements and 30-day mortality and potential diagnostic criteria for MINS (ie, myocardial injury due to ischemia associated with 30-day mortality). Prospective cohort study of patients aged 45 years or older who underwent inpatient noncardiac surgery and had a postoperative hsTnT measurement. Starting in October 2008, participants were recruited at 23 centers in 13 countries; follow-up finished in December 2013. Patients had hsTnT measurements 6 to 12 hours after surgery and daily for 3 days; 40.4% had a preoperative hsTnT measurement. A modified Mazumdar approach (an iterative process) was used to determine if there were hsTnT thresholds associated with risk of death and had an adjusted hazard ratio (HR) of 3.0 or higher and a risk of 30-day mortality of 3% or higher. To determine potential diagnostic criteria for MINS, regression analyses ascertained if postoperative hsTnT elevations required an ischemic feature (eg, ischemic symptom or electrocardiography finding) to be associated with 30-day mortality. Among 21&#x202f;842 participants, the mean age was 63.1 (SD, 10.7) years and 49.1% were female. Death within 30 days after surgery occurred in 266 patients (1.2%; 95% CI, 1.1%-1.4%). Multivariable analysis demonstrated that compared with the reference group (peak hsTnT <5 ng/L), peak postoperative hsTnT levels of 20 to less than 65 ng/L, 65 to less than 1000 ng/L, and 1000 ng/L or higher had 30-day mortality rates of 3.0% (123/4049; 95% CI, 2.6%-3.6%), 9.1% (102/1118; 95% CI, 7.6%-11.0%), and 29.6% (16/54; 95% CI, 19.1%-42.8%), with corresponding adjusted HRs of 23.63 (95% CI, 10.32-54.09), 70.34 (95% CI, 30.60-161.71), and 227.01 (95% CI, 87.35-589.92), respectively. An absolute hsTnT change of 5 ng/L or higher was associated with an increased risk of 30-day mortality (adjusted HR, 4.69; 95% CI, 3.52-6.25). An elevated postoperative hsTnT (ie, 20 to <65 ng/L with an absolute change &#x2265;5 ng/L or hsTnT &#x2265;65 ng/L) without an ischemic feature was associated with 30-day mortality (adjusted HR, 3.20; 95% CI, 2.37-4.32). Among the 3904 patients (17.9%; 95% CI, 17.4%-18.4%) with MINS, 3633 (93.1%; 95% CI, 92.2%-93.8%) did not experience an ischemic symptom. Among patients undergoing noncardiac surgery, peak postoperative hsTnT during the first 3 days after surgery was significantly associated with 30-day mortality. Elevated postoperative hsTnT without an ischemic feature was also associated with 30-day mortality.

The association between intraoperative cardiovascular changes and perioperative myocardial injury has chiefly focused on hypotension during noncardiac surgery. However, the relative influence of blood pressure and heart rate (HR) remains unclear. We investigated both individual and codependent relationships among intraoperative HR, systolic blood pressure (SBP), and myocardial injury after noncardiac surgery (MINS). Secondary analysis of the Vascular Events in Noncardiac Surgery Cohort Evaluation (VISION) study, a prospective international cohort study of noncardiac surgical patients. Multivariable logistic regression analysis tested for associations between intraoperative HR and/or SBP and MINS, defined by an elevated serum troponin T adjudicated as due to an ischemic etiology, within 30 days after surgery. Predefined thresholds for intraoperative HR and SBP were: maximum HR >100 beats or minimum HR <55 beats per minute (bpm); maximum SBP >160 mm Hg or minimum SBP <100 mm Hg. Secondary outcomes were myocardial infarction and mortality within 30 days after surgery. After excluding missing data, 1197 of 15,109 patients (7.9%) sustained MINS, 454 of 16,031 (2.8%) sustained myocardial infarction, and 315 of 16,061 patients (2.0%) died within 30 days after surgery. Maximum intraoperative HR >100 bpm was associated with MINS (odds ratio [OR], 1.27 [1.07-1.50]; P < .01), myocardial infarction (OR, 1.34 [1.05-1.70]; P = .02), and mortality (OR, 2.65 [2.06-3.41]; P < .01). Minimum SBP <100 mm Hg was associated with MINS (OR, 1.21 [1.05-1.39]; P = .01) and mortality (OR, 1.81 [1.39-2.37]; P < .01), but not myocardial infarction (OR, 1.21 [0.98-1.49]; P = .07). Maximum SBP >160 mm Hg was associated with MINS (OR, 1.16 [1.01-1.34]; P = .04) and myocardial infarction (OR, 1.34 [1.09-1.64]; P = .01) but, paradoxically, reduced mortality (OR, 0.76 [0.58-0.99]; P = .04). Minimum HR <55 bpm was associated with reduced MINS (OR, 0.70 [0.59-0.82]; P < .01), myocardial infarction (OR, 0.75 [0.58-0.97]; P = .03), and mortality (OR, 0.58 [0.41-0.81]; P < .01). Minimum SBP <100 mm Hg with maximum HR >100 bpm was more strongly associated with MINS (OR, 1.42 [1.15-1.76]; P < .01) compared with minimum SBP <100 mm Hg alone (OR, 1.20 [1.03-1.40]; P = .02). Intraoperative tachycardia and hypotension are associated with MINS. Further interventional research targeting HR/blood pressure is needed to define the optimum strategy to reduce MINS.

Myocardial injury is a frequent complication of surgical patients after having non-cardiac surgery that is strongly associated with perioperative mortality. While intraoperative anesthesia-related deaths are exceedingly rare, about 1% of patients undergoing non-cardiac surgery die within the first 30 postoperative days. Given the number of surgeries performed annually, death following surgery is the second leading cause of death in the United States. Myocardial injury after non-cardiac surgery (MINS) is defined as an elevation in troponin concentrations within 30&#xa0;days postoperatively. Although typically asymptomatic, patients with MINS suffer myocardial damage and have a 10% risk of death within 30&#xa0;days after surgery and excess risks of mortality that persist during the first postoperative year. Many factors for the development of MINS are non-modifiable, such as preexistent coronary artery disease. Preventive measures, systematic approaches to surveillance and treatment standards are still lacking, however many factors are modifiable and should be considered in clinical practice: the importance of hemodynamic control, adequate oxygen supply, metabolic homeostasis, the use of perioperative medications such as statins, anti-thrombotic agents, beta-blockers, or anti-inflammatory agents, as well as some evidence regarding the choice of sedative and analgesic for anesthesia are discussed. Also, as age and complexity in comorbidities of the surgical patient population increase, there is an urgent need to identify patients at risk for MINS and develop prevention and treatment strategies. In this review, we provide an overview of current screening standards and promising preventive options in the perioperative setting and address knowledge gaps requiring further investigation.

Myocardial injury after noncardiac surgery (MINS) is common and associated with short- and long-term major cardiovascular events. Diagnostic criteria for MINS using Abbott high-sensitivity cardiac troponin I (hs-cTnI) are unknown. We performed a prospective cohort study of adults who had in-patient noncardiac surgery and measured hs-cTnI (Abbott Laboratories) on postoperative serum samples collected up to postoperative day 3. The objective was to determine prognostically important hs-cTnI thresholds associated with major cardiac events and death at 30 days after noncardiac surgery. Using Cox proportional iterative analyses, we determined peak postoperative hs-cTnI thresholds associated with the occurrence of the 30-day composite of major cardiac events (ie, nonfatal myocardial infarction after 3 postoperative days, cardiac arrest, and congestive heart failure) and death. Of 3953 included patients, 66 (1.7%) experienced the primary outcome at 30 days. Peak hs-cTnI values and associated incidence of major cardiac events and death were as follows: < 60 ng/L: 1.0% (95% CI 0.7-1.3); 60 to < 700 ng/L: 8.6% (5.6-13.0); and &#x2265; 700 ng/L: 27.3% (16.4-41.9). Compared with peak hs-cTnI < 60 ng/L, adjusted hazard ratios were 7.54 (95% CI% 4.27-13.32) for hs-cTnI values of 60 to < 700 ng/L and 26.87 (13.27-54.41) for values &#x2265; 700 ng/L. Hs-cTnI elevation within the first 3 days after noncardiac surgery independently predicts major cardiac events and death at 30 days. A postoperative hs-cTnI &#x2265; 60 ng/L was associated with a > 7-fold increase in the risk of subsequent major cardiac events and mortality at 30 days.

Myocardial injury after non-cardiac surgery (MINS), based on measurement of troponin T, is associated with perioperative major adverse cardiovascular events (MACE). We therefore determined the high-sensitivity troponin I (hsTnI) thresholds associated with 30 day MACE after non-cardiac surgery. We performed a nested biobank cohort study of 4553 patients from the Vascular Events in Non-Cardiac Surgery Patients Cohort Evaluation (VISION) Study. We measured hsTnI (ADVIA Centaur&#xae; hsTnI assay) on postoperative days 1 to 3 in patients &#x2265;45 years undergoing non-cardiac surgery. An iterative Cox proportional hazard model determined peak postoperative hsTnI thresholds independently associated with MACE (i.e., death, myocardial infarction occurring on postoperative day 4 or after, non-fatal cardiac arrest, or congestive heart failure) within 30 days after surgery. MACE occurred in 89/4545 (2.0%) patients. Peak hsTnI values of <75 ng/L, 75 ng/L to <1000 ng/L, and &#x2265;1000 ng/L were associated with 1.2% (95% CI, 0.9-1.6), 7.1% (95% CI, 4.8-10.5), and 25.9% (95% CI, 16.3-38.4) MACE, respectively. Compared to peak hsTnI <75 ng/L, values 75 ng/L to <1000 ng/L and &#x2265;1000 ng/L were associated with adjusted hazard ratios (aHR) of 4.53 (95% CI, 2.75-7.48) and 16.17 (95% CI, 8.70-30.07), respectively. MACE was observed in 9% of patients with peak hsTnI &#x2265;75 ng/L vs 1% in patients with peak hsTnI <75 ng/L (aHR 5.76; 95% CI, 3.64-9.11). A peak hsTnI &#x2265;75 ng/L was associated with MACE in the presence (aHR 9.35; 95% CI, 5.28-16.55) or absence (aHR 3.99; 95% CI, 2.19-7.25) of ischemic features of myocardial injury. A peak postoperative hsTnI &#x2265;75 ng/L was associated with >5-fold increase in the risk of 30 days MACE compared to levels <75 ng/L. This threshold could be used for MINS diagnosis when the ADVIA Centaur hsTnI assay is used.Clinicaltrials.gov Registration Number: NCT00512109.