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Risk stratification of chest pain patients by point-of-care cardiac troponin T and myoglobin measured in the emergency department.

A prospective multicenter study including 1410 chest pain patients with suspected acute coronary syndromes was carried out to examine the predictive value of biological cardiac markers for adverse events measured by a point-of-care system. Admission cardiac troponin T (cTnT) and myoglobin were measured in parallel on a point-of-care system in the emergency department and -- together with CK-MB mass -- on lab analyzers. In a one-year follow-up, cardiac and non-cardiac death, acute myocardial infarction, unstable angina pectoris and need for revascularization were registered. Median time between onset of symptoms and admission was 285 min; 172 patients (12.2%) had no event during follow-up. If the cTnT, measured either by the point-of-care system or a conventional lab analyzer, was >0.05 microg/L, then the chance of a cardiac event during the follow-up period was doubled (18% vs. 9%). Serial cTnT measurement did not add any further value to the predictive power of the admission cTnT. Myoglobin and CK-MB mass identified increasing risk with increasing concentration quartiles; cardiac event rates were 2.8- to 4.4-fold higher between the quartiles with the lowest and those with the highest analyte concentration, respectively. There was no difference in non-cardiac death rates between any concentration quartiles. In conclusion, the prediction of clinical events by cardiac troponin T and myoglobin measured with a point-of-care analyzer in the emergency department was as good as that of the same cardiac markers and CK-MB mass measured on lab analyzers.

Aged↗

Pediatric brain natriuretic peptide and N-terminal pro-brain natriuretic peptide reference intervals.

BACKGROUND: Brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) have been shown to be useful biomarkers for the diagnosis of heart failure. Pediatric reference intervals for these analytes have been reported in part. Previous studies lack large numbers in each group, have not covered all age ranges and have not compared results for BNP with NT-proBNP in simultaneously drawn samples. METHODS: We measured BNP in whole blood using the Biosite Triage point-of-care method and plasma NT-proBNP using the Dade RxL Dimension. We assessed between and within-day precision of both methods and after removing outliers employed the Hoffmann approach to calculate pediatric reference intervals over the age range of 0-21 y. We also compared the 2 methods on simultaneously drawn samples. RESULTS: Reference intervals revealed approximately 20-fold higher 97.5th percentiles for neonates than for children >3 y of age. 97.5th percentiles decreased significantly over the first 3 years of life. As shown by others, the CVs for the automated Dade RxL platform were somewhat lower than those for the POCT method. BNP and NT-proBNP correlated well in simultaneously drawn samples (r=0.947). DISCUSSION: Reference intervals for BNP and NT-proBNP are far higher in neonates and infants than in children older than three years of age. The reasons for this are unknown but resemble the elevated CK-MBs and troponins also found in neonates, although the 97.5th percentiles for these latter 2 cardiac markers decrease more rapidly to values found in older children by 6 months of age.

Adolescent↗

Unusually high concentrations of cTnI and cTnT in a patient with catastrophic antiphospholipid antibody syndrome.

BACKGROUND: We present a case of a patient with catastrophic antiphospholipid antibody syndrome with unusually high concentrations of cardiac Troponin I (cTnI) and cardiac Troponin T (cTnT). Troponins are sensitive and specific markers of myocardial injury. The degree of their elevation, in the context of the chronic autoimmune condition of the patient, elicited a thorough investigation for the presence of interfering antibodies. METHODS: Cardiac markers, including total CK, CK-MB, cTnI, and cTnT, were measured in this patient over a period of 14 days after the onset of symptoms. In order to rule out a possible interference, serum samples were subjected to serial dilutions and were incubated with a blocking reagent (HBR) prior to analysis. RESULTS: The time release of the cardiac markers into the systemic circulation of this patient followed the typical pattern after a myocardial infraction. Serial dilutions of the samples, and incubation with the blocking reagent revealed no indication of the presence of interfering antibodies. CONCLUSIONS: The results strongly suggest that the extremely high concentrations of cTnT and cTnI in this patient were real and indicative of a massive myocardial infarction (MI). These may be the highest concentrations of cTnI and cTnT reported in the systemic circulation of a single patient.

Adult↗

Heart fatty acid binding protein in the rapid evaluation of myocardial damage following valve replacement surgery.

BACKGROUND: Myocardial damage occurs following valve replacement surgery. We estimated the value of heart fatty acid binding protein (H-FABP) in these patients. METHODS: Sixty elected patients were enrolled and distributed into single (group A) and double (group B) valve replacement groups. The clinical data were outlined and blood samples were collected perioperatively for determination of plasma levels of H-FABP, cardiac troponin-I (cTn-I), and CK-MB in both groups. RESULTS: 56 patients completed the study and no significant difference of clinical data was observed except CPB time and ACC time between groups. H-FABP level elevated quickly after reperfusion and peaked significantly earlier than cTn-I and CK-MB, it also declined rapidly but did not return to baseline at 24 h after reperfusion. Three markers' levels were all higher in group B than in group A after reperfusion with significant differences at their peaks and thereafter. Patients with postoperative complications had significantly higher H-FABP levels than usual. H-FABP peak level associated well with the length of CPB and ACC as well as with other 2 markers' peak levels in both groups. CONCLUSION: Compared with cTn-I and CK-MB, H-FABP is an earlier and potentially useful marker in the rapid evaluation of myocardial damage following valve replacement surgery with CPB.

Adult↗

Use of biomarkers in the emergency department and chest pain unit.

The use of biomarkers of cardiac injury in the emergency department (ED) and observation unit settings has several nuances that are different and, therefore, worthy of its own set of use guidelines. The markers that are used, however, are the same. The primary marker of choice continues to be cardiac troponin (Tn). Other markers that have been used because of the need in the ED for rapid triage have been myoglobin and fatty acid binding protein. In addition, some centers still prefer less sensitive and less specific markers such as creatine kinase myocardial band (CK-MB). More recently, a push has occurred to develop markers of ischemia, such as ischemia modified albumin (IMA),to determine which patients have ischemia, even in the absence of cardiac injury. As troponin assays become more sensitive and method for use becomes better understood, the use of these other markers are being relegated to lesser and lesser roles. Markers of ischemia are useful, but at present, despite some enthusiasm, are not ready for routine use. Before describing the recommendations for clinical use of biomarkers in the ED, a basic understanding of some of the science and measurement issues related to these analytes is helpful.

Acute Disease↗

Diagnostic utility of new immunoassays for the cardiac markers cTnI, myoglobin and CK-MB mass.

OBJECTIVES: We investigated the diagnostic value of a new system, the Innotrac Aio! immunoassays for troponin, myoglobin and CK-MB, in 270 samples from patients with ACS, after bypass surgery (CABG) or with stable heart failure in comparison to the respective Roche assays. RESULTS: The values of the cardiac markers assessed by the respective assays correlated (cTnT/cTnI Rho = 0.94, myoglobin Rho = 0.87, CK-MB Rho = 0.84). If values were dichotomised, we found a high concordance of test positive and negative classified patients by troponins with the respective assays. CONCLUSION: There is strong evidence that the Innotrac Aio! system for cTnI measurement can be used reliably.

Acute Disease↗

Acute pancreatitis mimicking myocardial infarction: evaluation with myocardial contrast echocardiography.

Acute pancreatitis has frequently been reported to be associated with transient electrocardiography changes mimicking myocardial infarction despite normal epicardial coronary arteries. Although these reports generally have not included simultaneous assessment of myocardial function, 1 previous report has documented suggestive electrocardiography changes associated with a transient regional wall-motion abnormality but normal epicardial coronary arteries. Although the origin of these findings is poorly understood, suggested mechanisms have included electrolyte abnormalities, a vagally mediated reflex, coronary vasospasm, and myonecrosis as a result of the release of pancreatic proteolytic enzymes. We report a case of acute pancreatitis with electrocardiography changes and a regional wall-motion abnormality despite normal epicardial coronary arteries. Myocardial contrast echocardiography performed in this patient to evaluate the coronary microcirculation allows further insight into the mechanism of these findings.

Adult↗

Creatine kinase-MB elevation after percutaneous coronary intervention predicts adverse outcomes in patients with acute coronary syndromes.

AIM: To study the relationship between outcomes and peak creatine kinase (CK)-MB levels after percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS). METHODS AND RESULTS: Peak CK-MB ratios (peak CK-MB level/upper limit of normal [ULN]) after PCI were analysed in 6164 patients with NSTE ACS from four randomized trials who underwent in-hospital PCI. We excluded 696 patients with elevated CK or CK-MB levels <24h before PCI; the primary analysis included 2384 of the remaining 5468 patients (43.6%) with CK-MB levels measured <==24h after PCI. The incidence of in-hospital heart failure (0.1%, 0.8%, 3.4%, 4.1%, and 6.1%; P<0.001), arrhythmias (0.8%, 1.9%, 6.9%, 4.1%, and 7.9%; P<0.001), cardiogenic shock (0.1%, 1.3%, 2.0%, 2.3%, and 2.6%; P=0.004), and mortality through 6 months (2.1%, 2.4%, 4.9%, 4.1%, and 5.7%, P=0.005) was increased with peak CK-MB ratios of 0-1, 1-3, 3-5, 5-10, and >10xULN, respectively. The continuous peak CK-MB ratio after PCI significantly predicted adjusted 6-month mortality (risk ratio, 1.06 per unit increase above ULN; 95% confidence interval, 1.01-1.11; P=0.017). CONCLUSIONS: Greater CK-MB elevation after PCI is independently associated with adverse outcomes in NSTE ACS. These results underscore the adverse implications of elevated CK-MB levels after PCI in this high-risk population.

Acute Disease↗

Troponin is more useful than creatine kinase in predicting one-year mortality among acute coronary syndrome patients.

AIMS: To compare the long-term prognostic value of troponins (Tn) vs. conventional cardiac biomarker creatine kinase (CK) and CK-MB across the spectrum of acute coronary syndromes (ACS). METHODS AND RESULTS: In the prospective, observational Canadian ACS Registry, 4627 patients with ACS were enrolled from 51 centres. The CK, CK-MB, Tn samples were analysed in each hospital clinical laboratory and the results related to the reference levels of the individual laboratories. The study cohort comprised 3138 (67.8%) patients who had both CK (or CK-MB) and Tn measurements during the first 24 h of hospitalisation. Vital status at one-year was determined by standardized telephone interview. 61.2% and 59.0% of patients had abnormal Tn and CK (or CK-MB) levels, respectively. Vital status at one-year was ascertained for 2950 patients (6% lost to follow-up). Among patients with normal CK (or CK-MB) levels, elevated Tn was associated with increased one-year mortality (odds ratio [OR] 2.06; 95% CI 1.37-3.11; P=0.001). Similarly, among patients with abnormal CK (or CK-MB) levels, abnormal Tn predicted higher one-year mortality (OR 1.83; 95% CI 1.14-2.93; P=0.01). In contrast, abnormal CK (or CK-MB) was not predictive of mortality after stratification by Tn status. In multivariable analysis controlling for other known prognosticators including creatinine, abnormal Tn (adjusted OR 1.78; 95% CI 1.30-2.44; P<0.001) but not CK/CK-MB was independently associated with increased one-year mortality. CONCLUSIONS: Elevated Tn was independently associated with worse outcome at one-year, while CK or CK-MB status did not provide incremental prognostic information. Our findings support the use of Tn in the risk stratification of unselected ACS patients.

Aged↗

Clinical significance of a new Q wave after cardiac surgery.

OBJECTIVE: The appearance of new Q waves on the electrocardiogram (ECG) after cardiac surgery has been traditionally considered a sign of major myocardial tissue damage. The aim of this study was to investigate the clinical significance of new Q waves appearing following cardiac surgery and to correlate them with the release of myocardial cell damage biomarkers. METHODS: 206 consecutive patients undergoing cardiac surgery were prospectively evaluated. A 12 lead ECG was recorded and cardiac troponin I and creatinekinase subfraction MB assayed the day before surgery, on arrival at the intensive care Unit. 4 and 18 h postoperatively and every morning until the fifth postoperative day. RESULTS: The incidence of new Q waves was 7.3%. Patients with isolated ECG findings had an uneventful postoperative course; on the contrary, when ECG changes were coupled with the release of myocardial necrosis biomarkers, patients had a complicated postoperative course. CONCLUSIONS: The association of a new Q wave and high levels of myocardial necrosis biomarkers is strongly associated with postoperative cardiac events. On the contrary, the isolated appearance of a new Q wave has no impact on the postoperative cardiac outcome.

Aged↗

On-pump versus off-pump coronary artery bypass grafting: more heat-shock protein 70 is released after on-pump surgery.

OBJECTIVES: The use of cardiopulmonary bypass in coronary artery bypass grafting (CABG) may contribute to the postoperative inflammatory response. The molecular chaperone heat-shock protein (HSP) 70 may be induced by ischemia, and has been detected both in the myocardium and in the circulation after CABG. In vitro, extracellular HSP70 may activate both innate and adaptive immunity. Hypothesizing that use of cardiopulmonary bypass (CPB) leads to more circulating HSP70, we explored the release of it in 10 patients undergoing CABG with the use of CPB, and in 10 patients undergoing off-pump surgery CABG (OPCAB). METHODS: Blood samples were taken preoperatively, twice peroperatively, 2 and 6 h postoperatively and the next day. Serum analyses were performed by means of immunoassays. RESULTS: We detected a significant difference in postoperative circulating HSP70 between on-pump and off-pump patients (median peaks of 2849 and 756 pg/ml, respectively, P < 0.01 2 h postoperatively). Interleukin-6 and -8 increased in all patients, without significant differences between the groups. Serum interleukin-10 increased at the end of the operation in 7 of 10 patients operated with cardiopulmonary bypass (median 51.7 pg/ml), but in none of the off-pump patients. Furthermore, in the first group, interleukin-10 correlated with the HSP70 concentration at the end of the operation, r = 0.75, P < 0.05. Serum markers of myocardial damage were higher in conventional than off-pump patients on day 1 postoperatively: median cardiac Troponin T was 0.358 and 0.126 microg/l, respectively, P < 0.01. Correspondingly, median creatine kinase-MB was 23.6 and 7.8 microg/l in on-pump and off-pump patients, respectively, P < 0.001. Peak HSP70 correlated with both Troponin T and creatine kinase-MB measured on day 1. CONCLUSIONS: Significantly more HSP70 was released into the circulation following conventional than following off-pump CABG. Circulating HSP70 may indicate cellular stress or damage. Furthermore, HSPs are suggested as immunoregulatory agents, and may be important in the host defence postoperatively.

Aged↗

The association of elevated creatine kinase-myocardial band on mortality after coronary artery bypass grafting surgery is time and magnitude limited.

OBJECTIVE: The joint European Society of Cardiology and American College of Cardiology consensus statement on myocardial necrosis after revascularization stated that any amount of myocardial necrosis as detected by cardiac enzymes should be labeled a myocardial infarct. However, it also stated that more data collection is necessary to better interpret the elevation of cardiac enzymes after coronary artery bypass grafting. We sought to determine if a single postoperative value of creatine kinase-myocardial band could be used as a risk factor to help predict mortality after coronary artery bypass surgery. METHODS: A retrospective analysis of prospectively collected data on 1161 patients undergoing first-time, isolated coronary artery bypass surgery utilizing normothermic cardiopulmonary bypass was conducted. Creatine kinase-myocardial band was measured the morning after surgery. Binary logistic regression, Cox proportional hazard models, and overlapping quintiles were used to illuminate the association between creatine kinase-myocardial band elevation and mortality after coronary artery bypass surgery. RESULTS: We found a threshold value of creatine kinase-myocardial band, 40 ng/mL, above which elevations were associated with increased death rates. This association held after adjustment for other factors known to contribute to postoperative mortality. However, after 1 year, there was no longer a statistically significant higher mortality associated with elevated creatinine kinase-myocardial band > 40 ng/mL. CONCLUSION: Elevation of creatine kinase-myocardial band the morning after surgery above a threshold 40 ng/mL is associated with an increased risk of mortality.

Aged↗

On-pump beating heart versus off-pump coronary artery bypass surgery-evidence of pump-induced myocardial injury.

OBJECTIVE: By maintaining native coronary blood flow in on-pump beating heart surgery (OnP-BH) and comparing with OPCAB strategy pump-related effects on myocardial injury and cardiac dysfunction could be specifically differentiated from ischemia/reperfusion-related consequences of surgical coronary revascularization. METHODS: In a randomized-prospective design, 40 elective patients with normal EF and three vessels coronary artery disease (left main disease excluded) were assigned to OPCAB or OnP-BH surgery. Before coronary occlusion and 1, 30, 60, and 90 min after reperfusion with the LIMA graft, coronary sinus (CS) blood was sampled to determine intraoperative myocardial ischemia (pH, lactate, pO2) and oxidative stress (malondialdehyde, MDA). Additionally to CS blood arterial blood was analyzed 4, 12, and 24 h postoperatively to determine myocardial necrosis (CK-MB, cardiac troponin I), myocardial dysfunction (NT-proBNP) and inflammation (C-reactive protein). RESULTS: Groups were identical with regards to age and gender (OPCAB 63.0+/-6.0 versus OnP-BH 65.3+/-3.9 y, 20% female patients). Number of grafts were 3.0+/-0.5 in OPCAB versus 2.9+/-0.3 in OnP-BH (n.s.) with 44 versus 34% bilateral IMAs and 56 versus 50% complete arterial revascularization. Regarding ischemia, intraoperatively only lactate values increased significantly in the OnP-BH group. Significantly higher CK-MB and troponin I levels were found from LIMA-LAD flow release onwards to 4 h postoperatively in the OnP-BH group. NT-proBNP levels were significantly higher in the OnP-BH group during the entire study period. CRP levels were higher in the OnP-BH group 12 and 24 h postoperatively. CONCLUSIONS: In this randomized study on routine coronary patients with normal ventricular function, OPCAB revealed less myocardial injury than OnP-BH. These findings implicate that CPB slightly affects the myocardium.

Aged↗

Intracoronary shunt reduces postoperative troponin leaks: a prospective randomized study.

OBJECTIVE: The purpose of this study was to evaluate whether intracoronary shunt usage reduced the myocardial damage on the basis of the cardiac markers when compared with the shuntless anastomosis in off-pump coronary artery bypass grafting (OPCABG) surgery of isolated left anterior descending artery lesions. METHODS: Forty patients who had stable angina with isolated left anterior descending (LAD) coronary artery lesion undergoing OPCABG surgery were randomized into two groups. Shunt group consisted of 20 patients who had OPCABG using intracoronary shunt, whereas the shuntless group consisted of 20 patients who underwent OPCABG without using intracoronary shunt. Cardiac troponin I, CK, and CK-MB before and 24h after the surgery were assessed in the groups. RESULTS: There were no deaths in the study. The two groups were similar with respect to sex and age. Duration of LIMA-LAD anastomosis was significantly higher in the shunt group (p=0.01). There was no significant difference between the groups concerning the preoperative and postoperative CK and CK-MB levels. The preoperative troponin I levels of the groups were not different (p=0.238; NS), whereas postoperative levels of this marker was significantly higher in the shuntless group (p=0.003). CONCLUSION: Intracoronary shunt reduced the postoperative troponin I levels significantly, so it may be indicated in the patients who are thought to be susceptible to transient ischemia.

Aged↗

The UW solution has greater potential for longer preservation periods than the Celsior solution: comparative study for ventricular and coronary endothelial function after 24-h heart preservation.

OBJECTIVE: Improvement of long-term heart preservation methods would potentially increase the donor pool and improve survival. We compared the efficacies of the University of Wisconsin (UW) and Celsior solutions on ventricular and endothelial functions after 24-h preservation. METHODS: We used an isolated heart preparation perfused with blood. The heart was excised from a rabbit, stored for 24 h in the UW or Celsior solution, and then perfused with blood from a support-rabbit. We evaluated cardiac output and coronary endothelial function. RESULTS: The Frank-Starling curve showed a significant left and upward shift in the UW group compared with that in the Celsior group (p<0.01). There were no significant differences between the groups for the coronary blood flow in response to sodium nitroprusside or acetylcholine. The serum creatine kinase MB level after reperfusion was significantly lower in the UW group than in the Celsior group (10.7+/-1.4 ng/mL vs 30.4+/-5.4 ng/mL, p<0.01), whereas lipid peroxide levels did not differ significantly between the two groups. CONCLUSIONS: The UW group showed better left ventricular function than the Celsior group, indicating that the UW solution has greater potential for long-term preservation than Celsior solution.

Adenosine↗

Impact of avoiding cardiopulmonary bypass for coronary surgery on perioperative cardiac enzyme release and survival.

OBJECTIVE: This study examines the association between avoiding the use of cardiopulmonary bypass (CPB) for coronary surgery and postoperative cardiac enzyme (CE) release, and its subsequent impact on survival. METHODS: Between January 1999 and September 2002, 3734 consecutive patients underwent either off-pump or on-pump coronary surgery. Patient characteristics and postoperative cardiac enzyme release were collected prospectively. Logistic regression was used to assess the effect of off-pump coronary surgery on cardiac enzyme release. All analyses were adjusted for preoperative characteristics and number of grafts. All patients were followed up at 1 year to assess survival. RESULTS: Nine hundred and sixty (25.7%) patients had off-pump coronary surgery. Seven hundred and twenty-six (19.4%) patients had cardiac enzyme release three to six times the upper limit of the reference range, while 266 (7.1%) patients had cardiac enzyme release more than six times the upper limit of the reference range. After adjusting for patient characteristics, off-pump surgery was associated with less release (cardiac enzyme release three to six times, adjusted odds ratio 0.43, p<0.001; cardiac enzyme release more than six times, adjusted odds ratio 0.59, p=0.005). Risk adjusted survival at 1 year was 97.5% for the on-pump group and 97.0% for the off-pump group (p=0.33). CONCLUSIONS: Avoiding cardiopulmonary bypass significantly reduces early cardiac enzyme release following coronary artery bypass grafting (CABG). However, it does not result in improved survival compared to coronary surgery using cardiopulmonary bypass. This absence of survival benefit may be due to higher mortality rates experienced by the fewer patients with high (>6 times the upper limit of range) cardiac enzyme release following coronary artery bypass surgery without cardiopulmonary bypass.

Aged↗

Evaluation of myocardial metabolism with microdialysis during bypass surgery with cold blood- or Calafiore cardioplegia.

BACKGROUND: For the first time, microdialysis was used to investigate in vivo and online the myocardial metabolism during and after cardiac surgery in patients treated with two different methods of myocardial protection. METHODS: Thirty patients underwent standard CABG with one of two different methods of myocardial protection. The patients were randomised to receive either cold blood (COLD group) or warm modified Calafiore cardioplegia (WARM group). Microdialysis probes were implanted into the myocardium of left ventricular apical region of the heart. Cardioplegia was given antegrade only. Microdialysis measurements were performed at time intervals before, during and 24 h after cardiopulmonary bypass and analysed for glucose, lactate, pyruvate and glycerol. RESULTS: Myocardial lactate concentrations were significantly higher in the WARM group compared with that of the COLD group, while serum lactate was comparable. Glycerol was significantly higher at the end of the clamping time in the WARM group. At the same time the glucose-lactate ratio as a marker of nutritional disorder had significantly lower levels in the WARM group. The cumulative CK-MB release over 24 h was significantly higher in those hearts protected with warm blood. CONCLUSIONS: The oxidative stress measured was significantly higher in patients undergoing CABG using modified Calafiore cardioplegia, whereas the cold cardioplegia minimised the effects of aortic clamping. The results indicate that cold cardioplegia offers superior protection of the heart, in terms of more rapid normalisation of myocardial metabolism. In elective myocardial revascularisation, intermittent antegrade warm blood cardioplegia is a comparable safe method of myocardial protection. However, in patients referring to a long clamping time, advantages of cold cardioplegia for myocardial revascularisation may be magnified.

Aged↗