Circadian rhythm of cardiac troponin I and its clinical impact on the diagnostic accuracy for acute myocardial infarction.

BACKGROUND: High-sensitivity cardiac troponin T (hs-cTnT) blood concentrations were shown to exhibit a diurnal rhythm, characterized by gradually decreasing concentrations throughout daytime, rising concentrations during nighttime and peak concentrations in the morning. We aimed to investigate whether this also applies to (h)s-cTnI assays and whether it would affect diagnostic accuracy for acute myocardial infarction (AMI). METHODS: Blood concentrations of cTnI were measured at presentation and after 1 h using four different cTnI assays: three commonly used sensitive (s-cTnI Architect, Ultra and Accu) and one experimental high-sensitivity assay (hs-cTnI Accu) in a prospective multicenter diagnostic study of patients presenting to the emergency department with suspected AMI. These concentrations and their diagnostic accuracy for AMI (quantified by the area under the curve (AUC)) were compared between morning (11 p.m. to 2 p.m.) and evening (2 p.m. to 11 p.m.) presenters. RESULTS: Among 2601 patients, AMI was the final diagnosis in 17.6% of patients. Concentrations of (h)s-cTnI as measured using all four assays were comparable in patients presenting in the morning versus patients presenting in the evening. Diagnostic accuracy for AMI of all four (h)s-cTnI assays were high and comparable between patients presenting in the morning versus presenting in the evening (AUC at presentation: 0.90 vs 0.93 for s-cTnI Architect; 0.91 vs 0.94 for s-cTnI Ultra; 0.89 vs 0.94 for s-cTnI Accu; 0.91 vs 0.94 for hs-cTnI Accu). CONCLUSIONS: Cardiac TnI does not seem to express a diurnal rhythm. Diagnostic accuracy for AMI is very high and does not differ with time of presentation. CLINICAL TRIAL REGISTRATION: NCT00470587, http://clinicaltrials.gov/show/NCT00470587.

Validation of NICE diagnostic guidance for rule out of myocardial infarction using high-sensitivity troponin tests.

OBJECTIVE: To validate the National Institute for Health and Care Excellence (NICE) recommended algorithms for high-sensitivity troponin (hsTn) assays in adults presenting with chest pain. METHODS: International post hoc analysis of three prospective, observational studies from tertiary hospital emergency departments. The primary endpoint was cardiac death or acute myocardial infarction (AMI) within 24 hours of presentation, and the secondary endpoint was major adverse cardiac events (MACE) at 30 days. RESULTS: 15% of patients were diagnosed with non-ST elevation myocardial infarction (MI) on admission. The hsTnI algorithm classified 2506/3128 (80.1%) of patients as 'ruled out' with 50 (2.0%) missed MI. 943/3128 (30.1%) of patients had a troponin I level below the limit of detection on admission with 2 (0.2%) missed MI. For the hsTnT algorithm, 1794/3374 (53.1%) of patients were 'ruled out' with 7 (0.4%) missed MI. 490/3374 (14.5%) of patients had a troponin T below the limit of blank on admission with no MI. MACE at 30 days occurred in 10.7% and 8.5% of patients 'ruled out' defined by the hsTnI and hsTnT algorithms, respectively. CONCLUSIONS: The NICE algorithms could identify patients with low probability of AMI within 2 hours; however, neither strategy performed as predicted by the NICE diagnostic guidance model. Additionally, the rate of MACE at 30 days was sufficiently high that the algorithms should only be used as one component of a more extensive model of risk stratification. TRIAL REGISTRATION NUMBER: ACTRN12611001069943, NCT00470587; post-results.

Use of copeptin and high-sensitive cardiac troponin T for diagnosis and prognosis in patients with diabetes mellitus and suspected acute myocardial infarction.

BACKGROUND: Diabetes is a major risk factor for acute myocardial infarction (AMI). Assessment of diabetic patients is challenging due to an often atypical presentation of symptoms. We aimed to evaluate the two novel biomarkers copeptin and high-sensitive cardiac troponin (hs-TnT) for the improvement of early diagnosis and risk-stratification in patients with diabetes and suspected AMI. METHODS: In this prospective international multicenter study we evaluated 379 patients with diabetes in a cohort of 1991 patients presenting with symptoms suggestive of AMI. The measurement of biomarkers was performed at presentation. RESULTS: Among the 379 diabetic patients, 32.7% had AMI, and in the 1621 patients without diabetes, 18.8% had AMI. The additional use of copeptin improved the diagnostic accuracy provided by conventional troponin alone (AUC 0.86 vs. 0.79, p=0.004). During a median follow-up of 814 days, 49 (13.1%) diabetic patients died. Cumulative 2-year survival rate for patients with copeptin levels below 9 pmol/l was 96.6% compared to 82.8% in patients above that level (p<0.001). The same was observed for hs-TnT with a cutoff level of 14 ng/l (97.7% vs. 82.0%, p<0.001) respective of cTnT with a cutoff level of 10 ng/l (93.5% vs. 75.6%, p<0.001). In multivariate Cox analysis, copeptin, hs-TnT and cTnT were strong and independent predictors of 24-month-mortality. Using the dual marker strategy (copeptin and troponin) identified two groups of high-risk patients where 22.5% of the group with hs-cTnT and copeptin above the cutoff and 28.6% with cTnT and copeptin above the cutoff died. CONCLUSION: In diabetic patients, copeptin only slightly improves the early diagnosis of AMI provided by hs-cTnT. However, both markers (copeptin and troponin) predict long-term mortality accurately and independently of each other.

Diagnostic and prognostic value of circulating microRNAs in patients with acute chest pain.

OBJECTIVES: To address the diagnostic value of circulating microRNAs (miRNAs) in patients presenting with acute chest pain. DESIGN: In a prospective, international, multicentre study, six miRNAs (miR-133a, miR-208b, miR-223, miR-320a, miR-451 and miR-499) were simultaneously measured in a blinded fashion in 1155 unselected patients presenting with acute chest pain to the emergency department. The final diagnosis was adjudicated by two independent cardiologists. The clinical follow-up period was 2 years. RESULTS: Acute myocardial infarction (AMI) was the adjudicated final diagnosis in 224 patients (19%). Levels of miR-208b, miR-499 and miR-320a were significantly higher in patients with AMI compared to those with other final diagnoses. MiR-208b provided the highest diagnostic accuracy for AMI (area under the receiver operating characteristic curve 0.76, 95% confidence interval 0.72-0.80). This diagnostic value was lower than that of the fourth-generation cardiac troponin T (cTnT; 0.84) or the high-sensitivity cTnT (hs-cTnT; 0.94; both P < 0.001 for comparison). None of the six miRNAs provided added diagnostic value when combined with cTnT or hs-cTnT (ns for the comparison of combinations vs. cTnT or hs-cTnT alone). During follow-up, 102 (9%) patients died. Levels of MiR-208b were higher in patients who died within 30 days, but the prognostic accuracy was low to moderate. None of the miRNAs predicted long-term mortality. CONCLUSION: The miRNAs investigated in this study do not seem to provide incremental diagnostic or prognostic value in patients presenting with suspected AMI.

Factors associated with positive blood cultures in outpatients with suspected bacteremia.

Blood cultures are routinely taken in outpatients with fever and suspected bacterial infections. However, in the majority of cases, they are not informative and of limited value for clinical decision making. The aim of this study was therefore to investigate factors associated with positive blood cultures in outpatients presenting to an outpatient clinic and emergency room. This was a case-control study of all outpatients with positive blood cultures from January 1, 2006 to October 31, 2007 and matched control patients with negative blood cultures in the same time period. Microbiology results and medical charts were reviewed to determine factors associated with positive blood cultures. The presence of a systemic inflammation response syndrome (SIRS) (OR 2.7, 95% Cl 1.0-7.2) and increased C-reactive protein (CRP) (OR 1.1 per 10 mg/l, 95% Cl 1.0-1.2) were the most powerful predictive values for the development of positive blood cultures. In positive cases serum albumin was lower (35 mg/l versus 39 mg/l) than in controls. SIRS, increasing CRP and low albumin were associated with positive blood cultures in outpatients. With simple clinical assessment and few laboratory tests indicative of infection, it is possible to define a group at higher risk for bacteremia in outpatients.