Glycocalyx Degradation and Inflammation in Cardiac Surgery.

OBJECTIVE: Experimental inflammation induces degradation of glycocalyx. The authors hypothesized that inflammation is an important determinant of glycocalyx degradation in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). DESIGN: A prospective observational study. SETTING: Operation theater and intensive care unit of a university hospital. PARTICIPANTS: Two separate prospective patient cohorts. INTERVENTIONS: Blood samples were collected at 5 perioperative time points in the trial cohort (30 patients) and only preoperatively in the preoperative cohort (35 patients). Plasma syndecan-1 (biomarker of glycocalyx degradation), interleukin-6 (IL-6), IL-8, and IL-10 were measured. MEASUREMENTS AND MAIN RESULTS: In the trial cohort, preoperative ranges were as follows: 0.8-198 ng/mL for syndecan-1; 0-902 pg/mL for IL-6; 0-314.9 pg/mL for IL-8, and 0-2,909 pg/mL for IL-10. Seven out of 30 patients were outliers in terms of plasma concentrations of syndecan-1 and all cytokines preoperatively. The increase of syndecan-1 was 2.7-fold, and those of IL-6 and IL-8 were both 2.5-fold. The increase of IL-10 was modest. Plasma syndecan-1 correlated with all cytokines preoperatively (IL-6: R = 0.66, p < 0.001; IL-8: R = 0.67, p = 0.001; IL-10: R = 0.73, p < 0.001) as well as at 6 hours postoperatively (IL-6: R = 0.49, p = 0.006; IL-8: R = 0.43, p = 0.02; IL-10: R = 0.41, p = 0.03) and on the postoperative morning (IL-6: R = 0.57, p = 0.001; IL-8: R = 0.37, p = 0.06; IL-10: R = 0.51, p = 0.005) but not intraoperatively. The preoperative findings of the trial cohort could be confirmed in the preoperative cohort. CONCLUSIONS: In patients undergoing cardiac surgery with CPB, inflammation in terms of proinflammatory cytokines IL-6 and IL-8 and anti-inflammatory cytokine IL-10 is associated with glycocalyx degradation measured as plasma syndecan-1 concentrations.

Postoperative Cardiac Ischemia Detection by Continuous 12-Lead Electrocardiographic Monitoring in Vascular Surgery Patients: A Prospective, Observational Study.

OBJECTIVES: Elderly patients undergoing vascular surgery are at major risk for perioperative cardiac complications. The authors investigated continuous electrocardiographic Holter monitoring in a postoperative setting to determine the degree of postoperative ischemic load and its possible associations with perioperative myocardial infarction. DESIGN: A prospective, observational study. SETTING: One university hospital. PARTICIPANTS: The study comprised 51 patients aged 65 years or older undergoing peripheral arterial surgery. INTERVENTIONS: Continuous electrocardiographic monitoring with a Holter device was started postoperatively and continued for 72 hours or until discharge. Postural changes were recorded using a 3-axis accelerometer. Standard 12-lead electrocardiography, high-sensitive troponin T measurements, and an inquiry of ischemic symptoms were performed 4 times perioperatively. MEASUREMENTS AND MAIN RESULTS: The primary outcomes were ischemic load (area under the function of ischemic ST-segment deviation and ischemic time) and perioperative myocardial infarction. During 3,262.7 patient-hours of monitoring, 17 patients (33.3%) experienced 608 transient ischemic events, all denoted by ST-segment depression. Of these 17 patients, 5 experienced perioperative myocardial infarction. The mean ischemic load in all patients was 913.2±2,797.3 µV×minute. Ischemic load predicted perioperative myocardial infarction, with an area under receiver operating characteristics curve (95% confidence interval) of 0.87 (0.75-0.99). Ischemic changes occurred most frequently during hours 24 to 60 of monitoring. Ischemia was asymptomatic in 14 of 17 patients (82.4%). CONCLUSION: Postoperative myocardial ischemia was common in peripheral vascular surgery patients and may progress to perioperative myocardial infarction. Ischemic load was a good predictor of perioperative myocardial infarction. Ambulatory electrocardiographic monitoring solutions for continuous postoperative ischemia detection are warranted in the surgical ward.

Acute Kidney Injury After Cardiac Surgery by Complete KDIGO Criteria Predicts Increased Mortality.

OBJECTIVES: Acute kidney injury (AKI) occurs frequently after cardiac surgery and is associated with increased mortality. The Kidney Disease: Improving Global Outcomes (KDIGO) criteria for diagnosing AKI include creatinine and urine output values. However, the value of the latter is debated. The authors aimed to evaluate the incidence of AKI after cardiac surgery and the independent association of KDIGO criteria, especially the urine output criterion, and 2.5-year mortality. DESIGN: Prospective, observational, cohort study. SETTING: Single-center study in a university hospital. PARTICIPANTS: The study comprised 638 cardiac surgical patients from September 1, 2011, to June 20, 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Hourly urine output, daily plasma creatinine, risk factors for AKI, and variables for EuroSCORE II were recorded. AKI occurred in 183 (28.7%) patients. Patients with AKI diagnosed using only urine output had higher 2.5-year mortality than did patients without AKI (9/53 [17.0%] v 23/455 [5.1%], p = 0.001). AKI was associated with mortality (hazard ratios [95% confidence intervals]: 3.3 [1.8-6.1] for KDIGO 1; 5.8 [2.7-12.1] for KDIGO 2; and 7.9 [3.5-17.6]) for KDIGO 3. KDIGO stages and AKI diagnosed using urine output were associated with mortality even after adjusting for mortality risk assessed using EuroSCORE II and risk factors for AKI. CONCLUSIONS: AKI diagnosed using only the urine output criterion without fulfilling the creatinine criterion and all stages of AKI were associated with long-term mortality. Preoperatively assessed mortality risk using EuroSCORE II did not predict this AKI-associated mortality.

Renal effects of levosimendan: a consensus report.

Renal dysfunction is common in clinical settings in which cardiac function is compromised such as heart failure, cardiac surgery or sepsis, and is associated with high morbidity and mortality. Levosimendan is a calcium sensitizer and potassium channel opener used in the treatment of acute heart failure. This review describes the effects of the inodilator levosimendan on renal function. A panel of 25 scientists and clinicians from 15 European countries (Austria, Finland, France, Hungary, Germany, Greece, Italy, Portugal, the Netherlands, Slovenia, Spain, Sweden, Turkey, the United Kingdom, and Ukraine) convened and reached a consensus on the current interpretation of the renal effects of levosimendan described both in non-clinical research and in clinical study reports. Most reports on the effect of levosimendan indicate an improvement of renal function in heart failure, sepsis and cardiac surgery settings. However, caution should be applied as study designs differed from randomized, controlled studies to uncontrolled ones. Importantly, in the largest HF study (REVIVE I and II) no significant changes in the renal function were detected. As it regards the mechanism of action, the opening of mitochondrial KATP channels by levosimendan is involved through a preconditioning effect. There is a strong rationale for randomized controlled trials seeking beneficial renal effects of levosimendan. As an example, a study is shortly to commence to assess the role of levosimendan for the prevention of acute organ dysfunction in sepsis (LeoPARDS).

[Perioperative cardiac infarction - an underdiagnosed problem]. / Perioperatiivinen sydäninfarkti - alidiagnosoitu ongelma.

Perioperative cardiac infarction (PMI) associated with surgery and the postoperative period significantly restricts the outcome of operative treatment. PMI is encountered in 0.5 to 1% of surgical patients, but among high-risk patients the incidence exceeds 10%. The disorder is associated with a mortality of 10 to 25%, corresponding to at least 1 000 patient deaths annually, as adjusted to the numbers of operative treatment in Finland, and its care requires at least 20000 extra days of hospitalization.

Effects of levosimendan on renal function in patients undergoing coronary artery surgery.

OBJECTIVES: To evaluate the effect of levosimendan on postoperative renal function in patients with compromised heart function undergoing on-pump coronary artery bypass graft surgery. DESIGN: A prospective, randomized, placebo-controlled, double-blind substudy. SETTING: Cardiothoracic surgery, anesthesiology, and intensive care units at 2 university hospitals. PARTICIPANTS: Sixty patients with left ventricular ejection fraction ≤50% were randomized into 2 parallel treatment groups. INTERVENTIONS: Levosimendan or placebo was started after the induction of anesthesia with a 12-µg/kg bolus in 10 minutes followed by the infusion of 0.2 µg/kg/min for the next 23 hours and 50 minutes. MEASUREMENTS AND RESULTS: Serum cystatin C and plasma creatinine were measured at baseline; at 6 and 24 hours after declamping the aorta; and on the 1st, 2nd, and 5th postoperative days. Urine N-acetyl-ß-glucosaminidase (U-NAG) was measured at baseline and at 6 and 24 hours after declamping of the aorta. Renal function was estimated with calculated glomerular filtration rate (eGFR). The changes in plasma creatinine, serum cystatin C, and urine NAG were not significant among the placebo and the levosimendan groups at any of the measuring points. CONCLUSIONS: After coronary artery surgery, levosimendan did not have a significant influence on the kidney function measured with these specific kidney markers.

[Neurologic complications in cardiac surgery patients]. / Sydänleikkauspotilaiden neurologiset komplikaatiot.

Cerebral infarction and hypoxic-ischemic brain damage (HIE) may impair the recovery of a patient from otherwise successful cardiac operation. Severe neurologic complications occur in approximately 2 to 5% of cardiac surgery patients. The major risk factors can be recognized. The most common cause of cerebral infarction is a calcific embolus released during manipulation of atheromatotic aorta. HIE results from cerebral circulatory deficiency and subsequent hypoxia in the cerebral tissue. The development of complications can be prevented by restricting aortic manipulation and by optimizing the perfusion technique and other treatment during the operation.

Renal effects of dexmedetomidine during coronary artery bypass surgery: a randomized placebo-controlled study.

BACKGROUND: Dexmedetomidine, an alpha2-adrenoceptor agonist, has been evaluated as an adjunct to anesthesia and for the delivery of sedation and perioperative hemodynamic stability. It provokes dose-dependent and centrally-mediated sympatholysis. Coronary artery bypass grafting (CABG) with extracorporeal circulation is a stressful procedure increasing sympathetic nervous system activity which could attenuate renal function due the interrelation of sympathetic nervous system, hemodynamics and renal function. We tested the hypothesis that dexmetomidine would improve kidney function in patients undergoing elective CABG during the first two postoperative days. METHODS: This was a double-blind, randomized, parallel-group study. Patients with normal renal function and scheduled for elective CABG were randomized to placebo or to infusion of dexmedetomidine to achieve a pseudo steady-state plasma concentration of 0.60 ng/ml. The infusion was started after anesthesia induction and continued until 4 h after surgery. The primary endpoint was creatinine clearance. Other variables included urinary creatinine and output, fractional sodium and potassium excretion, urinary potassium, sodium and glucose, serum and urinary osmolality and plasma catecholamine concentrations. The data were analyzed with repeated-measures ANOVA or Cochran-Mantel-Haenszel test. RESULTS: Sixty-six of 87 randomized patients were evaluable for analysis. No significant between-group differences were recorded for any indices of renal function except for a mean 74% increase in urinary output with dexmedetomidine in the first 4 h after insertion of a urinary catheter (p < 0.001). Confidence interval examination revealed that the sample size was large enough for the no-difference statement for creatinine clearance. CONCLUSIONS: Use of intravenous dexmedetomidine did not alter renal function in this cohort of relatively low-risk elective CABG patients but was associated with an increase in urinary output.This study was carried out in 1994-1997 and was thus not registered.

An evaluation of the epidural catheter position by epidural nerve stimulation in conjunction with continuous epidural analgesia in adult surgical patients.

BACKGROUND: The epidural stimulation test to confirm epidural catheter position has been described as being simple, fast, and reliable. We evaluated the feasibility of the epidural stimulation test and its potential in contributing to effective postoperative continuous epidural analgesia. METHODS: Thirty adult patients (ASA I-III) undergoing major abdominal surgery or thoracotomy were to receive continuous epidural analgesia at a thoracic level postoperatively. The epidural stimulation test was performed after catheter placement, after local anesthetic boluses, and during epidural analgesia, up to six times in each patient. Catheter positions were verified by epidurography (before start of epidural analgesia and again on the second postoperative day). RESULTS: Several technical issues (e.g., need to flush catheter with saline in order to maintain adequate stimulation during >25% of all measurements) and interpretation problems (e.g., interference of respiratory activity [n = 6]) made the implementation of the epidural stimulation test rather time consuming, both at the time of catheter placement and during epidural analgesia. Immediately after catheter placement (before test dose) the epidural stimulation test did not identify four of four catheters positioned outside the spinal canal. In addition, the initial epidural stimulation test indicated a possible intrathecal or paravertebral placement in 3 of 25 catheters correctly positioned in the epidural space. During 107 of 122 (88%) measurements with the catheter tip situated epidurally and with preceding or simultaneous administration of epidural local anesthetic, the epidural stimulation test elicited a motor response. Continuous epidural analgesia provided adequate pain relief in all 25 patients having positive epidurography. CONCLUSIONS: The epidural stimulation test was often associated with technical difficulties and interpretation problems. The role of the repeated use of the epidural stimulation test for quality assurance in patients undergoing postoperative continuous epidural analgesia remains undetermined.

Levosimendan in perioperative and critical care patients.

PURPOSE OF REVIEW: To present recent experiences and studies on the pharmacologic profile of levosimendan in the context of surgery, anesthesia and critical care. Special emphasis is on the studies that could support the use of or create novel indications for levosimendan in these patients. RECENT FINDINGS: Several controlled studies now suggest that levosimendan is efficacious in improving hemodynamics in patients after cardiac surgery. Its use as an adjunct to catecholamines instead of phosphodiesterase inhibitors can be recommended in patients with postcardiotomy heart failure and cardiogenic shock. Prophylactic administration before cardiopulmonary bypass in patients with compromised ventricular function may also be rational because levosimendan facilitates weaning from cardiopulmonary bypass without inotropes with higher myocardial oxygen cost of inotropy. This mode of administration also seems to attenuate troponin release and spares treatment resources such as duration of postoperative ventilation and ICU stay. The reported experience in patients with noncardiac surgery is meager but previous results obtained from nonsurgical patients should be largely applicable. The use of levosimendan in treating septic myocardial depression or sepsis syndrome is a promising option but remains investigational for today. SUMMARY: New practice advisories and proposals for indications to treat and prevent low-output syndrome in patients at risk are warranted for patients undergoing cardiac surgery with cardiopulmonary bypass. Levosimendan should also be considered as an adjunct drug for the treatment of cardiogenic shock. Further experience and controlled studies are needed to support the use of levosimendan for other perturbations in critical care and perioperative medicine.

The effect of N-acetylcysteine on blood coagulation and platelet function in patients undergoing open repair of abdominal aortic aneurysm.

N-acetylcysteine (NAC) may offer renal and hepatic protection during surgery, but in experimental studies it has been shown to impair coagulation. Since very little is known about the effects of NAC on blood coagulation in surgical patients, we studied its effects during abdominal aortic reconstruction. NAC (a bolus of 150 mg/kg followed by a continuous 24-h infusion of 150 mg/kg) or the same volume of placebo was given intravenously, in a randomized double-blinded fashion, to 20 patients undergoing abdominal aortic aneurysm repair. The haematocrit, platelet count, prothrombin time, thromboelastometry, and platelet aggregation were studied during and after surgery. Total blood loss was also measured. The median (25th-75th percentiles) decrease of the prothrombin time value was 33.0% (30-37%) after NAC treatment and 6.5% (4-8%) after placebo (P<0.001). Postoperative prothrombin time values remained lower in the patients receiving NAC. In thromboelastometry tracings the coagulation time was more prolonged after the bolus of NAC (P=0.02). Platelet aggregation induced with adenosine diphosphate decreased after NAC but not after placebo. Low prothrombin time values before and after bolus infusions were associated with increased blood loss (P=0.008 and P=0.015, respectively). NAC has anticoagulant and platelet-inhibiting properties in patients undergoing major vascular surgery. This abnormal haemostatic activity should be considered when NAC is administered to patients with increased bleeding risk.

N-acetylcysteine for the prevention of kidney injury in abdominal aortic surgery: a randomized, double-blind, placebo-controlled trial.

In this prospective, randomized, placebo-controlled, double-blind trial we studied the effects of IV N-acetylcysteine for prevention of renal injury in patients undergoing abdominal aortic surgery. Seventy patients without previously documented renal dysfunction were randomly allocated to receive either N-acetylcysteine (150 mg/kg mixed in 250 mL of 5% dextrose infused in 20 min, followed by an infusion of 150 mg/kg in 250 mL of 5% dextrose over 24 h) or placebo. The infusion was started after the induction of anesthesia. The primary outcome measure was renal injury as measured by the increases in urinary N-acetyl-beta-d-glucosaminidase (NAG)/creatinine ratio (indicator of renal tubular injury) and urinary albumin/creatinine ratio (indicator of glomerular injury). Renal function was assessed by measuring plasma creatinine and serum cystatin C concentrations. The urinary NAG/creatinine ratio increased significantly from baseline to before crossclamp and remained increased on day 5 in both groups. The urinary albumin/creatinine ratio increased significantly from baseline to 6 h after declamping in the N-acetylcysteine group. However, the changes in the NAG/creatinine ratio and the albumin/creatinine ratio were not significantly different between the two groups. Plasma creatinine and serum cystatin C values remained unchanged during the study period in both groups. In conclusion, N-acetylcysteine did not offer any significant protection from renal injury during elective aortic operation in patients with normal preoperative renal function, and some degree of tubular injury seems to occur before aortic crossclamp.

Predictive value of high-sensitivity troponin T in addition to EuroSCORE II in cardiac surgery.

OBJECTIVES: Plasma troponins, measured by fourth-generation assays, are associated with increased mortality and morbidity after cardiac surgery. They also offer predictive information in addition to EuroSCORE, a widely used risk model after cardiac surgery. However, preoperatively measured troponin has provided no additional information to postoperative values. Whether these facts hold true also for the high-sensitivity fifth-generation troponin assay and the better calibrated risk model, EuroSCORE II, is unknown. We hypothesized that preoperative and/or postoperative high-sensitivity troponin T (hs-TnT) would increase the predictive value of EuroSCORE II. METHODS: Consecutive coronary artery bypass grafting (CABG) and other cardiac surgical patients were prospectively enrolled in a university hospital. Plasma samples and EuroSCORE II variables were collected. The primary and secondary end-points were 180-day mortality and any major adverse event within 30 days, and 961-day mortality. The data were analysed by Kaplan-Meier survival curves, regression analyses, receiver operator characteristic curves and decision curve analysis. RESULTS: Mortality rates in 180 days were 3.5% (15/428) in CABG and 6.4% (14/220) in other cardiac surgical patients. Survival curves differed only in patients with not only high postoperative hs-TnT value (>500 ng/l), but also high preoperative hs-TnT value (>14 ng/l), compared with patients with both hs-TnT values low. Adding hs-TnT to EuroSCORE II improved the prediction of 180-day mortality in other cardiac surgical patients (maximum net benefit of 1.5%), but not in CABG patients. Regarding major adverse events, adding hs-TnT to EuroSCORE II improved the prediction in both CABG patients and other cardiac surgical patients (maximum net benefits of 3 and 7%). CONCLUSIONS: Elevated postoperative hs-TnT was predictive of mortality only when combined with elevated preoperative hs-TnT. Hs-TnT measurements added information to the EuroSCORE II regarding major adverse events in all cardiac surgical patients and regarding 180-day mortality in non-CABG patients.

Levosimendan: molecular mechanisms and clinical implications: consensus of experts on the mechanisms of action of levosimendan.

The molecular background of the Ca(2+)-sensitizing effect of levosimendan relates to its specific interaction with the Ca(2+)-sensor troponin C molecule in the cardiac myofilaments. Over the years, significant preclinical and clinical evidence has accumulated and revealed a variety of beneficial pleiotropic effects of levosimendan and of its long-lived metabolite, OR-1896. First of all, activation of ATP-sensitive sarcolemmal K(+) channels of smooth muscle cells appears as a powerful vasodilator mechanism. Additionally, activation of ATP-sensitive K(+) channels in the mitochondria potentially extends the range of cellular actions towards the modulation of mitochondrial ATP production and implicates a pharmacological mechanism for cardioprotection. Finally, it has become evident, that levosimendan possesses an isoform-selective phosphodiesterase-inhibitory effect. Interpretation of the complex mechanism of levosimendan action requires that all potential pharmacological interactions are analyzed carefully in the framework of the currently available evidence. These data indicate that the cardiovascular effects of levosimendan are exerted via more than an isolated drug-receptor interaction, and involve favorable energetic and neurohormonal changes that are unique in comparison to other types of inodilators.

The effect of levosimendan on bupivacaine-induced severe myocardial depression in anesthetized pigs.

BACKGROUND AND OBJECTIVES: Levosimendan, an inodilator without proarrhythmogenic properties, has been shown to reverse ropivacaine-induced negative inotropy in isolated heart preparations. In this randomized and blinded study, we investigated whether levosimendan is able to reverse rapidly bupivacaine-induced myocardial depression in pigs. METHODS: Twenty invasively monitored pigs anesthetized with isoflurane 1% received bupivacaine 2 mg/kg per minute into a central vein until mean arterial pressure decreased to 55% of baseline. Thereafter, levosimendan 80 microg/kg for 10 mins, followed by 0.7 microg/kg per minute during the next 50 mins (L-SIM) or corresponding amounts of placebo were administered intravenously. Simultaneously, Ringer's acetate was infused intravenously, 20 mL/kg for 10 mins, followed by 20 mL/kg for 50 mins. RESULTS: Two pigs in each group developed cardiac arrest immediately after bupivacaine and could not be resuscitated. Bupivacaine induced widening of the QRS complex in the electrocardiogram and bradycardia.In the remaining 16 pigs, 3 (2 in L-SIM group and 1 in placebo group) needed short-lasting manual cardiac compression and 1 dose of epinephrine. Cardiac output, ejection fraction, and stroke power/end-diastolic volume recovered initially very rapidly in the L-SIM group.However, there was no time x group effect difference in the overall recovery in the various parameters between the 2 groups, except in heart rate which was higher (P G 0.05) when levosimendan was administered.During the 50-min levosimendan infusion, mean arterial pressure and systemic vascular resistance stayed slightly lower in comparison with placebo infusion, but the difference was not statistically significant. CONCLUSIONS: Levosimendan together with the infusion of Ringer's solution rapidly reversed the cardiac depression, but there was no difference in overall cardiovascular recovery in comparison to treatment with Ringer's solution alone. Levosimendan-induced increase in heart rate possibly facilitated the recovery from bupivacaine intoxication.

Serum cystatin C in elderly cardiac surgery patients.

BACKGROUND: Elderly cardiac surgery patients are more prone to develop postoperative acute kidney injury (AKI). The common clinical glomerular filtration marker, plasma creatinine, is considered to be inadequate to discover AKI in its early stage. The aim of this study was to determine if serum cystatin C can detect mild renal failure earlier than plasma creatinine. METHODS: From 110 cardiac surgery patients aged 70 or greater years, serum cystatin C and plasma creatinine samples were collected preoperatively and on postoperative days 1 to 5. Their urine output, creatinine, and estimated glomerular filtration rate were calculated and AKI was determined by the risk-injury-failure-loss-end-stage kidney disease criteria (RIFLE). The correlation of plasma creatinine and serum cystatin C to AKI was calculated. RESULTS: After cardiac surgery, 62 of the 110 patients (56.4%) developed AKI according to the RIFLE classification. In this group, both serum cystatin C and plasma creatinine peaked on postoperative day 3. Cystatin C and creatinine correlated equally with AKI at different time points calculated with receiver operating characteristic curves. On postoperative day 1 the area under the curve (AUC) for creatinine was 0.66 (0.55 to 0.76) and for cystatin C 0.71 (0.61 to 0.81); Delta AUC 0.05 (0.01 to 0.12), p = 0.11. On postoperative day 2 the AUC for creatinine was 0.74 (0.64 to 0.83) and for cystatin was C 0.77 (0.68 to 0.86); Delta AUC -0.03 (-0.09 to 0.03), p = 0.32. CONCLUSIONS: Elderly cardiac surgery patients have a high incidence of AKI, as defined by the RIFLE criteria. After cardiac surgery serum cystatin C and plasma creatinine detected AKI similarly.

Biochemical injury markers and mortality after coronary artery bypass grafting: a systematic review.

The strength of the association between cardiac biomarker release and prognosis is uncertain. We performed a systematic literature search to find articles regarding these markers and death after coronary surgical interventions, and evaluated the results with meta-analytic methods. We found 23 articles concerning 29,483 patients that reported the MB fraction of creatine kinase (CK-MB) and troponin T and I. Heterogeneity of existing studies prevented the pooling of the results of troponin studies. The pooled data of the CK-MB studies suggest that after coronary artery bypass grafting, CK-MB release of more than five to eight times the upper limit of the reference range is associated with an increased risk of death during the next 40 months.