cTnI Measurements Research Articles

New insights in the pathophysiology of acute myocardial infarction detectable by a contemporary troponin assay

ObjectivesST-elevation and non-ST-elevation myocardial infarction (STEMI, NSTEMI) are considered two distinct pathophysiologic entities. We evaluated cardiac troponin I (cTnI) release in STEMI and NSTEMI using a “contemporary” (CV>10 to 20% at the 99th percentile concentration) cTnI assay for patients undergoing early percutaneous coronary intervention (PCI). Design and methods856 patients with suspected acute coronary syndrome consecutively admitted to the Emergency Department of the Maggiore Hospital of Novara (225 STEMI and 135 NSTEMI) were selected according to: 1) early (≤4h from admission) and successful PCI; and 2) cTnI measurements at ED presentation and within 24h. The influence of the MI type on cTnI concentrations at baseline and after PCI as well as the velocity of cTnI [cTnI V=absolute increase (after log conversion of cTnI measurements)/delay between the two measurements] was studied by multiple regression analysis, adjusting for patient parameters. ResultsA statistically significant interaction between MI type and time from symptoms was reported on cTnI concentrations (p<0.0001): STEMI and NSTEMI differed for cTnI releases at admission and after revascularization. Higher cTnI V in STEMI was detectable in patients admitted within 6h from symptoms. Baseline cTnI concentrations were lower in patients with a history of coronary artery disease (CAD) and increased with aging (p<0.0001). In the elderly (>75years), the cTnI V was significantly increased. ConclusionSTEMI and NSTEMI patients have different patterns and dynamics of cTnI release influenced by the interaction with time from symptoms, by aging and history of CAD.

Randomised Assessment of Treatment using Panel Assay of Cardiac markers – Contemporary Biomarker Evaluation (RATPAC CBE)

To test the diagnostic accuracy for detecting an acute myocardial infarction (AMI) using highly sensitive troponin assays and a range of new cardiac biomarkers of plaque destabilisation, myocardial ischaemia and necrosis; to test the prognostic accuracy for detecting adverse cardiac events using highly sensitive troponin assays and this range of new cardiac biomarkers; and to estimate the cost-effectiveness of using highly sensitive troponin assays or this range of new cardiac biomarkers instead of an admission and 10- to 12-hour troponin measurement. Substudy of the point-of-care arm of the RATPAC (Randomised Assessment of Treatment using Panel Assay of Cardiac markers) trial. The emergency departments of six hospitals. Prospective admissions with chest pain and a non-diagnostic electrocardiogram randomised to point-of-care assessment or conventional management. Blood samples taken on admission and 90 minutes from admission for measurement of cardiac markers [cardiac troponin I (cTnI), myoglobin and creatine kinase MB isoenzyme (CK-MB)] by point-of-care testing. An additional blood sample was taken at admission and 90 minutes from admission for analysis of high-sensitivity cTnI (two methods) and cardiac troponin T (cTnT), myoglobin, heart-type fatty acid-binding protein (H-FABP), copeptin and B-type natriuretic peptide (NTproBNP). 1. Diagnostic accuracy compared with the universal definition of myocardial infarction utilising laboratory measurements of cardiac troponin performed at the participating sites together with measurements performed in a core laboratory. 2. Ability of biomarker measurements to predict major adverse cardiac events (death, non-fatal AMI, emergency revascularisation or hospitalisation for myocardial ischaemia) at 3 months' follow-up. 3. Comparison of incremental cost per quality-adjusted life-year (QALY) of different biomarker measurement strategies for the diagnosis of myocardial infarction. Samples were available from 850 out of 1132 patients enrolled in the study. Measurement of admission myoglobin [area under the curve (AUC) 0.76] and CK-MB (AUC 0.84) was diagnostically inferior and did not add to the diagnostic efficiency of cTnI (AUC 0.90-0.94) or cTnT (AUC 0.92) measurement on admission. Simultaneous measurement of H-FABP and cTnT or cTnI did improve admission diagnostic sensitivity to 0.78-0.92, but only to the same level as that achieved with troponin measured on admission and at 90 minutes from admission (0.78-0.95). Copeptin (AUC 0.62) and NTproBNP (AUC 0.85) measured on admission were not useful as diagnostic markers. As a prognostic marker, troponin measured on admission using a high-sensitivity assay (AUC 0.73-0.83) was equivalent to NTproBNP measurement (AUC 0.77) on admission, but superior to copeptin measurement (AUC 0.58). From modelling, 10-hour troponin measurement is likely to be cost-effective compared with rapid rule-out strategies only if a £30,000 per QALY threshold is used and patients can be discharged as soon as a negative result is available. The measurement of high-sensitivity cardiac troponin is the best single marker in patients presenting with chest pain. Additional measurements of myoglobin or CK-MB are not clinically effective or cost-effective. The optimal timing for measurement of cardiac troponin remains to be defined. Copeptin measurement is not recommended. H-FABP requires further investigation before it can be recommended for simultaneous measurement with high-sensitivity troponin in patients with acute chest pain. ISRCTN37823923. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 15. See the HTA programme website for further project information.

VALUE OF CARDIAC TROPONIN I FOR PREDICTING IN-HOSPITAL OCCURRENCE OF HYPOTENSION IN STABLE PATIENTS WITH ACUTE PULMONARY EMBOLISM

Although cardiac troponin I (cTnI) elevations during acute pulmonary embolism (PE) are predictive of in-hospital death, it is not clear whether cTnI measurements at emergency department (ED) admission are predictive of the occurrence of hypotension. The study subjects included all consecutive patients with acute PE (diagnosed by chest computed tomography angiography) in the ED between January 2006 and December 2011. All underwent cTnI tests at ED admission and were divided into two groups based on the occurrence of hypotension within 24 h. Of 457 stable patients with acute PE who were admitted to the ED during the study period, 301 patients were included. Within 24 h of hospitalization, 27 (9.0%) developed hypotension. The patients who developed hypotension had a significantly higher mean cTnI concentration than did the remaining patients (1.01 vs. 0.14 ng/mL, P < 0.00). They were also more likely to be treated with thrombolytic therapy and had higher 28-day and 6-month mortality rates. Cardiac TnI elevation (>0.05 ng/mL) at ED admission was a strong predictor of the development of hypotension within 24 h (odds ratio, 8.2; 95% confidence interval, 2.6-26.1; P = 0.00). The sensitivity, specificity, positive predictive value, and negative predictive value of elevated cTnI were 85%, 66%, 20%, and 98%, respectively. This study suggests that a normal cTnI nearly rules out subsequent development of hypotension within 24 h. This may help to select those patients who would benefit most from intensive clinical surveillance and escalated treatment.

Longitudinal Studies of Cardiac Troponin I in a Large Cohort of Healthy Children

There is little information available on cardiac troponin concentrations in healthy young children. Using a precommercial high-sensitivity assay from Abbott Diagnostics, we measured cardiac troponin I (cTnI) in longitudinal blood samples collected at ages 8, 10, and 12 years from a cohort of healthy, community-dwelling children. The 99th percentile values were calculated and estimates of the long-term biological variation were made. cTnI concentrations were above the limit of detection in 87%, 90%, and 98% of the children at ages 8, 10, and 12 years. The 99th percentiles were lower compared to a healthy adult population in both male and female children at all ages studied. At the 3 periods of study assessment, different children had cTnI concentrations above the 99th percentile. The calculated 99th percentile varied markedly depending upon whether the lowest or highest cTnI measurement for an individual child was included in the calculation. Biological variation varied markedly between 0% and 136%, the index of individuality was low at 0.36, and the reference change value was an increase of 147% or a decrease of 59%. In this longitudinal study of cTnI concentrations in healthy children as determined by a high-sensitivity assay, different children had concentrations of cTnI above the 99th percentile at the 3 episodes of assessment. These results suggest that in children the 99th percentile may not be a reliable index of silent cardiac disease, but rather may be indicating low-grade intercurrent illness.

Abstract 9507: Noise vs. Signal: The Clinical Implications of A High Sensitivity Troponin Assay in the Evaluation of Possible Acute Coronary Syndrome

Objectives: To evaluate the real-world impact of a switch from conventional troponin I (cTnI) measurement to a high-sensitivity (hsTnI) assay in patients with acute coronary syndromes (ACS). Methods: This was a retrospective analysis of ACS cases from a single hospital system in the 3 months before and after a troponin assay switch. Outcomes included admitting diagnosis, initial treatment and diagnostic testing, need for coronary artery intervention (i.e., stent placement), in-hospital events, and final discharge diagnosis. Descriptive statistics and univariate comparisons by assay group were performed. Results: 783 ACS cases (mean age 60.9 yrs; 52.9% male; 77.7% black) were identified, 330 (42.1%) before and 453 (57.9%) after the assay change with no difference in demographics by assay period. An admitting diagnosis of NSTEMI was more common after the assay change (43.0% vs. 70.4%; p &lt; 0.001) as was the proportion with a positive troponin (32.1% vs. 71.3%; p &lt; 0.001). While aspirin (92.4% vs. 91.4%; p = 0.79), beta-blocker (76.1% vs. 80.8%; p = 0.09) and clopidogrel (50.9% vs. 46.6%; p = 0.25) use was similar, anticoagulants were used more often after the assay change (45.8% vs. 56.3%; p = 0.004). Echocardiography was also more common (39.7% vs. 47.0%; p = 0.05), but cardiac catheterization was less frequent (53.6% vs. 41.7%; p = 0.003) with no difference in the proportion who underwent stent placement (52.4% vs. 50.0%; p = 0.72). In-hospital event rates (Table) were equivalent. At discharge, diagnosis of NSTEMI was more likely post-assay change (27.9% vs. 36.6%; p = 0.011). Conclusions: After the switch to a hsTnI assay, more ACS patients had a positive test result and a greater proportion were diagnosed with NSTEMI at admission. Despite this, cardiac catheterization was used less frequently and coronary artery intervention as well as in-hospital event rates were flat, highlighting the uncertainty that surrounds a positive troponin in an era of high-sensitivity assays.

Dynamics of equine infectious anemia virus (EIAV) infection in naturally infected mules

African horse sickness (AHS) is a severe, non-contagious, insect-borne disease that causes high mortality in horses. Little information is available on the effects of AHS on clinical parameters. The objective of this study was to evaluate the cardiac system to aid on treatment and prognosis of AHS. Horses hospitalized at the Onderstepoort Veterinary Academic Hospital with confirmed AHS were included in the study after owner’s consent. Physical examination, base-apex ECG, echocardiography and serum cardiac troponin I (cTnI) were evaluated at different times until horses were either discharged or euthanized. A total of 11 horses were included, 6 survived and 5 were euthanized. Mean (range) heart rate at arrival was 59 (42-76) beats per minute. Tachycardia was present in 81% of the horses at arrival, 5/6 horses at discharge and in 4/5 horses at the time of euthanasia. cTnI was elevated at arrival in 2/6 survivors and 4/5 of the euthanized horses; however it increased above normal values (>0.03 ng/ml) in 10/11 horses as the disease progressed. Electrocardiography and echocardiography were normal in all horses at all times. This is the first report of cardiac evaluation in horses with AHS. Tachycardia and myocardial damage were common findings even at discharge. Serial cTnI measurements may be useful to evaluate disease progression and prognosis. cTnI needs to be evaluated before return to exercise is considered. Drugs that may affect the cardiac system function should be avoided. Abnormalities were not detected by ECG or echocardiography even when performed frequently.

Rapid and sensitive cardiac troponin I immunoassay based on fluorescent europium(III)-chelate-dyed nanoparticles

BackgroundCardiac troponins are the preferred and recommended biomarkers of myocardial infarction. Unfortunately, most of the current commercial assays do not meet the guideline recommendations for sensitivity and low-end precision. Therefore, improvements in their analytical performance are still needed. MethodsCardiac troponin I (cTnI) immunoassay was developed. The assay utilized a monoclonal antibody and a F(ab')2 antibody fragment immobilized onto the microtiter wells for capturing, and a monoclonal antibody covalently conjugated to fluorescent europium(III)-chelate-dyed nanoparticles for detecting. Following a 15-min incubation of the sample and nanoparticle-bioconjugates in the capture wells, cTnI was quantified directly from the washed well surface by time-resolved fluorometry. ResultsThe limits of detection and quantification were 0.0020μg/l and 0.012μg/l, respectively. The response was linear in the measured range of 0.003–9.6μg/l. The within-run imprecisions were 9.8, 5.1, 7.7 and 5.4%, and the total imprecisions were 13.1, 10.4, 9.0 and 8.7% at cTnI levels of 0.007, 0.051, 0.52 and 2.62μg/l, respectively. Plasma recoveries of added cTnI were 72–119%. Regression analysis with Innotrac Aio! 2nd generation cTnI assay yielded a slope (95% confidence intervals) of 1.197 (1.141 to 1.253) and y-intercept of 0.216 (−0.128 to 0.561)μg/l (Syx=2.176μg/l, n=212, r=0.945). ConclusionsThe developed immunoassay based on europium(III)-chelate-dyed nanoparticle label allows rapid and sensitive measurement of cTnI.

Usefulness of cardiac biomarkers in the prediction of right ventricular dysfunction before echocardiography in acute pulmonary embolism

BackgroundThe aim of this study was to investigate a useful cardiac biomarker for predicting echocardiographic right ventricular (RV) dysfunction in patients with acute pulmonary embolism (APE). MethodsA total of 84 patients with APE were divided into two groups: patients with RV dysfunction (group I, n=51, 61.8±15.1 years) versus without RV dysfunction (group II, n=33, 66.8±13.6 years). Cardiac biomarkers were compared between the groups. ResultsThe level of N-terminal pro-brain-type natriuretic peptide (NT-proBNP), cardiac specific troponin T (cTnt), and I (cTni) was significantly elevated in group I compared to group II, but the level of creatine kinase and high-sensitivity C-reactive protein was not different. By receiver operating characteristic curve analysis, the area under the curve to predict RV dysfunction was 0.912 for NT-proBNP, 0.797 for cTnt, and 0.766 for cTni. The optimal cut-off value to predict RV dysfunction was 620.0pg/mL for NT-proBNP (sensitivity: 90.2%, specificity: 75.8%), 0.016ng/mL for cTnt (sensitivity: 82.4%, specificity: 78.8%), and 0.055ng/mL for cTni (sensitivity: 86.3%, specificity: 66.7%). NT-proBNP>620pg/mL and cTnt>0.016ng/mL were independent predictors of RV dysfunction on multivariate analysis after adjustment for the baseline characteristics. ConclusionsNT-proBNP, cTnt, and cTni were significant serologic predictors of RV dysfunction in APE. Measurements of NT-proBNP, cTnt, and cTni are simple and useful in the risk stratification or treatment of APE.

Cardiac Troponin I elevation after epileptic seizure

BackgroundCardiac troponin-I (cTNI) is highly specific biomarker to prove myocardial damage, e.g. in acute coronary syndrome (ACS). However, it occurs in other conditions as well. We therefore analysed cTNI increase in patients after generalized convulsive seizure.MethodsConsecutive patients admitted with acute generalized convulsive seizure were included in case of cTNI measurement on admission. Among 898 selected cases, 53 patients were referred secondary to our department; in 845 cases cTNI measurements on admission were available. In case of multiple admissions (81 cases), only the first admission entered our analysis. In 17 patients elevated cTNI was determined due to ACS; in one patient a myocarditis was found. 5 patients suffered of relevant renal insufficiency. Finally 741 patients were included in the analysis. A cTNI cut-off level of ≥ 0.1 ng/ml was considered. Factors associated with a cTNI increase were analysed subsequently.ResultsThe mean age of the study population (n = 741) was 47.8 years (SD ± 18.6), 40.9% were female. In 50 patients (6.7%) a cTNI elevation of unknown origin was found; no obvious cardiac involvement could be detected in these patients who all remained asymptomatic. A vascular risk profile (including at least hypertension, hypercholesterolemia or diabetes) (OR = 3.62; CI: 1.59 to 8.21; p = 0.001) and elevated creatine kinase on admission (OR = 2.36; CI: 1.26 to 4.39; p = 0.002) were independent factors associated with cTNI release.ConclusioncTNI release occurs in patients with generalized convulsive seizure with predominance in patients with vascular risk profile.

Troponin Elevation Predicts Atrial Fibrillation in Patients with Stroke or Transient Ischemic Attack

Atrial fibrillation (AF) is a major cause of ischemic stroke. Cardiac troponin (cTnI) is a marker of myocardial damage and may predict arrhythmia. We sought to determine if increased cTnI levels were a predictor of new-onset AF in ischemic stroke or patients with transient ischemic attack (TIA). Consecutive patients who presented to Charles-Lemoyne Hospital between October 2006 and November 2010 with a diagnosis of acute ischemic stroke or TIA, without a history of AF, with a baseline measurement of cTnI were included in the study. The primary outcome was new-onset AF on 24-hour Holter measurement within 1 week of admission in patients without AF on the baseline electrocardiogram (ECG). Secondary outcomes included AF on Holter measurement, death, myocardial infarction (MI), and stroke within 3 months. A total of 408 patients were included. Forty-six patients (11.3%) had elevated cTnI levels. These patients were older and had a higher prevalence of coronary artery disease and diabetes. AF on baseline ECG or 24-hour Holter measurement was present in 51 patients (12.5%) and was more frequent among patients with increased cTnI levels compared to patients with normal cTnI levels (34.7% vs 9.7%; P = .004 multivariate analysis). Elevated cTnI levels also predicted the composite outcome of stroke, MI, and death at 3 months (50.0% vs 16.1%; P = .0001). cTnI elevation predicts new-onset AF on 24-hour Holter measurement in patients with acute ischemic stroke or TIA and may indicate a poorer prognosis and a higher risk of stroke, MI, and death at 3 months.

Comparison of heart-type fatty acid binding protein and cardiac troponin I for early detection of myocardial infarction after coronary bypass surgery

Objectives: Heart-type fatty acid binding protein (hFABP) is as a novel marker to detect myocardial injury shortly after onset of ischemia. We therefore compared cardiac troponin I (cTnI), which is most sensitive and specific for myocardial infarction, with hFABP in respect of fast and reliable response following coronary artery bypass grafting (CABG). Methods: One-hundred-eight consecutive patients undergoing isolated CABG with cardiopulmonary bypass were enrolled in this prospective, observational study. Serial blood samples were taken preoperatively, at 1, 6, 12, and 24h after surgery; electrocardiograms, clinical data and adverse events were recorded. hFABP and cTnI were analyzed using a combined quantitative bedside assay (CardioDetect® combi, Rennessens GmbH, Berlin, Germany). Postoperative myocardial infarction (PMI) was defined as a cTnI-elevation (>10ng/ml) within the first 24h after surgery. Results: Fourteen out of 108 patients (group1) were identified with PMI following the PMI criteria mentioned above, whereas 94 patients had no PMI and thus, were used as controls (group2). As a result, both hFABP and cTnI were significantly increased in group 1 compared to group 2 (P<0.001; ANOVA), hFABP however separated much earlier within 1h after CABG between group 1 and 2, whereas cTnI differed not until 12h after surgery between groups. A hFABP level of 20µg/mL at 1h after CABG best detected the presence of PMI with an area under the receiver operating characteristic (ROC) curve of 78.3% (sensitivity:93%, specificity:68%). Conclusion: hFABP is a highly sensitive biomarker, which detects PMI reliably as soon as 1h after CABG surgery and thus much earlier than standard cTnI measurement.

Cardiac troponin I and creatine kinase MB isoenzyme in patients with chronic renal failure.

The aim of our study was to evaluate cut-off values for acute coronary syndrome (ACS) diagnosis in patients with chronic renal failure (CRF) for the cardiac biomarkers cardiac troponin I (cTnI) and creatine kinase MB isoenzyme (CK-MB) as compared to the cut-off values proposed by the manufacturers and those frequently used in the laboratory. We performed a prospective study in patients with CRF with a glomerular filtration rate estimated by the MDRD-4 equation <60 mL/min and admitted with suspected acute coronary syndrome due to clinical history, physical examination, and electrocardiography. cTnI and CK-MB measurements were assessed upon hospitalisation and six months later using two different analytical methods (for cTnI: Access® and Vidas® analysers, and for CK-MB: Access® and Vitros® analysers). During the study period, 484 patients with CRF and suspected ACS were assessed. ACS was diagnosed in 12% of patients (58/484), while we found other cardiac pathologies (OCP) in 29% of patients (140/484) and other non-cardiac pathologies (ONCP) in 59% of patients (286/484). For cTnI assessed using the Access® analyser with the usual cut-off value (≥ 0.5 ng/mL), sensitivity was 43% and specificity was 94%, while for the proposed cut-off value (≥ 0.11 ng/mL), the values were 68% and 83%, respectively. For cTnI assessed using the Vidas® analyser with the usual cut-off value (≥ 0.11 ng/mL), sensitivity was 64% and specificity was 87%, while for the proposed cut-off value (≥ 0.06 ng/mL), the values were 75% and 79%, respectively. The sensitivity and specificity for both CK-MB were lower compared with cTnI. The cut-off values proposed in this study for both cTnI in patients with CRF (stage 3 to 5) to diagnose ACS are significantly different from that of the general population.

Circulating Troponin As Measured by a Sensitive Assay for Cardiovascular Risk Assessment in Primary Prevention

Measuring circulating cardiac troponin using novel sensitive assays has revealed that even minute elevations are associated with increased mortality in patients with coronary artery disease or even in the general population. Less well defined, however, is the incremental value of measuring circulating cardiac troponin I (cTnI) by a sensitive assay for risk assessment in primary prevention. We measured circulating concentrations of cTnI, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hsCRP) in 5388 individuals free of known cardiovascular disease recruited into the DETECT study, a prospective longitudinal population-based cohort study. We determined the prognostic implications for incident major adverse cardiovascular events (MACE) during 5 years of follow-up. Circulating cTnI was detectable in 19% of the subjects. Increased cTnI concentrations were associated with established risk factors for atherosclerosis and demonstrated a graded relationship with all-cause mortality and incident MACE during 5-year follow-up. A single measurement of cTnI significantly improved risk prediction over established risk factors, and also added prognostic information, when adjusted for serum concentrations of NT-proBNP and hsCRP. Minute increases in cTnI are associated with increased mortality and incident MACE in a large primary prevention cohort and, thus, identify contributors to cardiovascular risk not fully captured by traditional risk factor assessment.

NT-pro-BNP and troponin I as predictors of mortality in dogs with heart failure

The purpose of this study was to develop prognostic models for heart failure in dogs with dilated cardiomyopathy (DCM). The prospective study included 26 dogs with DCM and 58 healthy dogs. The ervation time median was 250 days (1-600 days). All the dogs were clinically examined, had echocardiography, electrocardiography, and morphological and biochemical blood sampling. Twenty four deaths were found in the group of dogs with DCM and 1 demise in the healthy dog's group. There was a significant increase in the level of NT-pro-BNP and cTnI (p < 0.0005) in the group of dogs with DCM and a significant higher level of NT-pro-BNP and cTnI (p < 0.0005) in the dead dogs from group with DCM that died or were euthanized up to the 60th day of observation, compared to the animals that outlasted over 60 days of observation. The median level of NT-pro-BNP in the dogs which had short survival period (no more than 60 days) was 4865 pmol/L and the median level of cTnI in the same group of dogs was 0.63 ng/ml. The median level of NT-pro-BNP in the group of dogs with DCM, which lived longer than 60 days of observation was 978 pmol/l and the median level of cTnI in this group was 0.1 ng/ml. The level of NT-pro-BNP (r = 0.79) and cTnI (r = 0.4) correlated with the dogs' death. NT-pro-BNP and cTnI measurements could be useful to evaluate the survival the dogs with DCM. Increased level of NT-pro-BNP and cTnI is a bad prognosis. In the performed analysis of the Cox hazard regression it was found that cTnI level has a significant impact of the survival of the dogs (HR = 8.54; Cl 1.1-46.6; p = 0.02).

Very early diagnosis of chest pain by point-of-care testing: comparison of the diagnostic efficiency of a panel of cardiac biomarkers compared with troponin measurement alone in the RATPAC trial

ObjectiveTo assess the impact of triple marker testing on patient management and the diagnostic efficiencies of different biomarker strategies examined.DesignA prospective randomised trial of triple marker testing by point-of-care testing...

Cost implications of the use of troponin I (cTnI) measurement to diagnose heart conditions

Abstract Focal points

Diagnostic accuracy of heart-type fatty acid–binding protein for the early diagnosis of acute myocardial infarction

ObjectiveThe aim of this study was to evaluate the diagnostic efficacy of multiple tests—heart-type fatty acid–binding protein (H-FABP), cardiac troponin I (cTnI), creatine kinase-MB, and myoglobin—for the early detection of acute myocardial infarction among patients who present to the emergency department with chest pain. MethodsA total of 1128 patients provided a total of 2924 venous blood samples. Patients with chest pain were nonselected and treated according to hospital guidelines. Additional cardiac biomarkers were assayed simultaneously at serial time points using the Cardiac Array (Randox Laboratories Ltd, Crumlin, United Kingdom). ResultsHeart-type fatty acid–binding protein had the greatest sensitivity at 0 to 3 hours (64.3%) and 3 to 6 hours (85.3%) after chest pain onset. The combination of cTnI measurement with H-FABP increased sensitivity to 71.4% at 3 to 6 hours and 88.2% at 3 to 6 hours. Receiver operating characteristic curves demonstrated that H-FABP had the greatest diagnostic ability with area under the curve at 0 to 3 hours of 0.841 and 3 to 6 hours of 0.894. The specificity was also high for the combination of H-FABP with cTnI at these time points. Heart-type fatty acid–binding protein had the highest negative predictive values of all the individual markers: 0 to 3 hours (93%) and 3 to 6 hours (97%). Again, the combined measurement of cTnI with H-FABP increased the negative predictive values to 94% at 0 to 3 hours, 98% at 3 to 6 hours, and 99% at 6 to 12 hours. ConclusionTesting both H-FABP and cTnI using the Cardiac Array proved to be both a reliable diagnostic tool for the early diagnosis of myocardial infarction/acute coronary syndrome and also a valuable rule-out test for patients presenting at 3 to 6 hours after chest pain onset.

Cardiac Troponins T and I: Reproducible Discrepancies in the Clinical Setting

To the Editor: The universal definition of myocardial infarction includes the increase and/or decrease in cardiac biomarkers, with at least 1 value greater than the 99th-percentile upper reference limit, concurrently with evidence of myocardial ischemia and corresponding clinical symptoms, electrocardiographic changes, or imaging evidence (1). Among cardiac biomarkers, cardiac troponins, including cardiac troponin I (cTnI)1 and cardiac troponin T (cTnT), have become the gold standard. Several noncardiac etiologies for increases in cardiac troponins have been described, however (2), and discordant values for cTnT and cTnI have been encountered in the clinical setting. The aim of our study was to systematically compare a cTnT assay and a cTnI assay with regard to discrepant values. This study was conducted in accord with the World Medical Association Declaration of Helsinki (3). We used the Architect cTnI STAT Troponin-I assay (Abbott Diagnostics) and the new high sensitive troponin T (hsTnT) assay (Troponin T hs) on the Modular Analytics system (Roche Diagnostics) to make 9004 simultaneous cTnI and cTnT measurements on 3995 patients and then analyzed the data. Because we were concerned about major discrepancies, we used 0.032 μg/L as the cutoff value for both the cTnI and hsTnT measurements. After applying this cutoff to our …

Early myocardial injury is an integral component of experimental acute liver failure - a study in two porcine models.

IntroductionThere is accumulating clinical evidence that acute liver failure may be regularly associated with myocardial injury. To test this hypothesis in a standardized experimental setting, we used two porcine models of ALF.Material and methodsIn 14 domestic pigs ALF was induced by either a) surgical devascularization of the liver (DV group, n = 7), or b) partial (70-75%) hepatectomy and ischaemia/reperfusion of the liver remnant for 150 min (I/R group, n = 7). Four additional animals constituted the sham operation group. All animals were monitored for a 12-h period, at the end of which their hearts were harvested. Plasma troponin I (cTnI) and malondialdehyde (MDA) were measured before the operation (baseline) and at 6 h and 12 h postoperatively. The harvested hearts were histologically analysed, appointing a score from 0 (no injury) to 3 (maximum injury) to selected injury indicators.ResultsIn the sham group, all cTnI measurements and total myocardial injury score were zero in all animals. In both ALF groups, plasma cTnI levels increased by the 6th and remained elevated up to the 12th postoperative hour (p < 0.01 vs. sham animals). Total myocardial injury score and total histological score revealed some extent of myocardial injury. The rise of MDA levels suggests an underlying oxidative mechanism.ConclusionsOur study provides direct evidence of early myocardial injury in the setting of acute liver failure in pigs. The mechanism of injury remains to be elucidated.

Combined Measurements of Cardiac Troponin I and Brain Natriuretic Peptide Are Useful for Predicting Adverse Outcomes in Hypertrophic Cardiomyopathy

Although serum cardiac troponin I (cTnI) and plasma brain natriuretic peptide (BNP) have become clinically important tools as diagnostic and prognostic markers for ischemic heart disease and heart failure, the usefulness of these biomarkers for risk stratification of hypertrophic cardiomyopathy (HCM) is not clear. We studied 167 patients with HCM, and cTnI and BNP were measured. During follow-up (38.5 months), 20 patients suffered from cardiovascular events: HCM-related deaths in 6, hospitalization for heart failure in 8, embolic stroke in 5 and 1 patient with spontaneous sustained ventricular tachycardia. Patients with high cTnI values (≥0.04 ng/ml) had more frequent cardiovascular events than did those with low cTnI values (P=0.008). Similarly, there were more frequent adverse events in the high BNP group (≥200 pg/ml) than in the low BNP group (P=0.002). When groups were allocated according to both cTnI and BNP measurements, serum cTnI used in conjunction with BNP further improved the prognostic value; patients with both high cTnI and BNP values had an 11.7-fold increased risk of cardiovascular events compared with those with both low cTnI and BNP values. CTnI and BNP are useful parameters for identifying patients at risk for clinical deteriorations, and combined measurements of these biomarkers further improves the prognostic value of increased cardiovascular events in HCM.