Clinical evaluation of the first medical whole blood, point-of-care testing device for detection of myocardial infarction

BACKGROUND: Validation of whole blood, point-of-care testing devices for monitoring cardiac markers to aid clinicians in ruling in and ruling out myocardial infarction (MI) is necessary for both laboratory and clinical acceptance. METHODS: This study evaluated the clinical diagnostic sensitivity and specificity of the First Medical Cardiac Test device operated by nursing and laboratory personnel that simultaneously measures cardiac troponin I (cTnI), creatine kinase (CK) MB, myoglobin, and total CK on the Alpha Dx analyzer in whole blood for detection of MI. Over a 6-month period, 369 patients initially presenting to the emergency department with chest pain were evaluated for MI using modified WHO criteria. Eighty-nine patients (24%) were diagnosed with MI. RESULTS: In whole blood samples collected at admission and at 3- to 6-h intervals over 24 h, ROC curve-determined MI decision limits were as follows: cTnI, 0.4 microgram/L; CKMB, 7.0 microgram/L; myoglobin, 180 microgram/L; total CK, 190 microgram/L. Based on peak concentrations within 24 h after presentation, the following sensitivities (+/- 95% confidence intervals) were found: cTnI, 93% +/- 5.5%; myoglobin, 81% +/- 9.7%; CKMB, 90% +/- 6.3%; total CK, 86% +/- 7.5%. Sensitivities were maximal at >90% for both cTnI and CKMB at >12 h in MI patients, without differences between ST-segment elevation and non-ST-segment elevation MI patients. CONCLUSIONS: The First Medical point-of-care device provides cardiac marker assays that can be used by laboratories and clinicians in a variety of hospital settings for ruling in and ruling out MI.     

Assessing the requirement for the 6-hour interval between specimens in the American Heart Association Classification of Myocardial Infarction in Epidemiology and Clinical Research Studies

BACKGROUND: The American Heart Association (AHA) case definition for acute myocardial infarction (AMI) requires an "adequate set" of biomarkers: 2 measurements of the same marker at least 6 h apart. A sensitive troponin assay might detect significant changes in concentration earlier. We determined AMI prevalence, using protocols with shorter intervals between measurements, with and without incorporating the time from onset of symptoms. METHODS: The AHA case definition was used to retrospectively assign a diagnosis in 258 patients presenting to the emergency department with symptoms of cardiac ischemia. AMI was diagnosed if either specimen in an adequate set had a cardiac troponin I (cTnI) above the 99th percentile (AccuTnI >0.04 microg/L; Beckman Coulter) with a > or =20% change in concentration between specimens. We assessed positivity for AMI after progressively decreasing the time interval between specimens in specimen sets. In addition, for each patient, 2 additional specimen pairs were selected: pairs collected at least 1 h apart with 1 specimen being either > or =3 h after onset or > or =6 h after onset. RESULTS: When we used the AHA definition, the AMI prevalence was 35.7%. Prevalence was not significantly diminished when the interval between specimens was > or =5, > or =4, or > or= 3 h (36.4%, 34.5%, and 33.7%, respectively) compared with the AHA > or =6 h interval. When the time from onset of symptoms was included in the specimen selection algorithm, a 1-h interval was sufficient provided that at least one specimen was collected > or =6 h after onset (prevalence, 34.1%; P = 0.48 vs AHA definition). CONCLUSION: A sensitive cTnI assay in specimen sets with time intervals > or =3 h, or having one specimen > or =6 h after onset, gave an AMI prevalence equivalent to the AHA definition.     

Clinical and experimental results on cardiac troponin expression in Duchenne muscular dystrophy

BACKGROUND: Because of controversial earlier studies, the purpose of this study was to provide novel experimental and additional clinical data regarding the possible reexpression of cardiac troponin T (cTnT) in regenerating skeletal muscle in Duchenne muscular dystrophy (DMD). METHODS: Plasma from 14 patients (mean age, 7.5 years; range, 5.7-19.4 years) with DMD was investigated for creatine kinase (CK), the CK MB isoenzyme (CKMB), cTnT and cardiac troponin I (cTnI), and myoglobin. cTnT concentrations were measured by an ELISA (second-generation assay; Roche) using the ES 300 Analyzer. cTnI, myoglobin, and CKMB were measured by an ELISA using the ACCESS System (Beckman Diagnostics). Troponin isoform expression was studied by Western blot analysis in remnants of skeletal muscle biopsies of three patients with DMD and in an animal model of DMD (mdx mice; n = 6). RESULTS: There was no relation of cTnT and cTnI to clinical evidence for cardiac failure. cTnI concentrations remained below the upper reference limit in all patients. cTnT was increased (median, 0.11 microg/L; range, 0.06-0.16 microg/L) in 50% of patients. The only significant correlation was found for CK (median, 3938 U/L; range, 2763-5030 U/L) with age (median, 7.5 years; range, 6.8-10.9 years; r = -0.762; P = 0.042). Western blot analysis of human or mouse homogenized muscle specimens showed no evidence for cardiac TnT and cTnI expression, despite strong signals for skeletal muscle troponin isoforms. CONCLUSIONS: We found no evidence for cTnT reexpression in human early-stage DMD and in mdx mouse skeletal muscle biopsies. Discrepancies of cTnT and cTnI in plasma samples of DMD patients were found, but neither cTnT nor cTnI plasma concentrations were related with other clinical evidence for cardiac involvement.     

Improved early risk stratification and diagnosis of myocardial infarction, using a novel troponin I assay concept

BACKGROUND: We evaluated the clinical performance of a novel cardiac troponin I (cTnI) assay specifically designed to improve the very early risk stratification in acute coronary syndromes. SUBJECTS AND METHODS: Serum and plasma samples (taken 0, 6-12 h and 24 h after admission) from 531 patients with suspected acute coronary syndrome were studied using a novel investigational cTnI assay, reference cTnI assay and myoglobin. The lowest cTnI concentration giving a total assay imprecision of 10% was used as the positive myocardial infarction (MI) cut-off value. RESULTS: At the time of admission, the investigational assay was positive in 27.9% of the patients, the reference cTnI assay was positive in only 17.5% (P < 0.001) and myoglobin in 24.1% (P = 0.067). Receiver operating characteristic (ROC) curve analysis for the detection of myocardial injury on admission gave area-under-curve (AUC) values of 0.937, 0.775 and 0.762, respectively (P < 0.001). Of those MI patients who presented within 3 h of symptom onset, 50.0% were identified by the investigational assay at the time of presentation, compared with 44.2% by myoglobin (P = 0.791) but only 11.5% by the reference assay (P < 0.001). CONCLUSIONS: The novel cTnI assay considerably improves the performance of cTnI as an early rule-in biomarker for MI.     

心肌标志物作用的系统分析

目的：获取心肌生化标记物的最佳应用证据。方法：查循、浏览对心肌肌酸激酶同工酶MB（CK－MB）、肌红蛋白、心肌肌钙蛋白T（cTnT）和心肌肌钙蛋白I（cTnI）用于诊断心肌梗塞（MI）和对急性冠状动脉综合症分级的系统评价和Meta－分析的文献资料。结果：在症状发生后的12－48小时采样分析CK－MB质量对于诊断MI的临床灵敏度和牧场划性分别是98．8％和89．6％。肌红蛋白有高的阴性预示值,在症状发生后的2－6小时采样分析有高的临床灵敏度。在症状发生后的12采样cTnI,诊断MI的临床灵敏度和特异性分别是98．2％和68．8％,其临床特异性降低与检测到微小心肌受损有关。结论：cTnT和cTnI比CK－MB对诊断心肌梗死和预测急性冠状动脉综合症危险性更有价值。     

Diagnosis and risk stratification of patients with anginal pain and non-diagnostic electrocardiograms

Patients with acute chest pain suggestive of myocardial ischaemia, and normal or non-diagnostic electrocardiograms, form a difficult subgroup for diagnosis and early risk stratification. We prospectively evaluated the role of troponin T (cTnT), troponin I (cTnI), CKMB mass and myoglobin, in the diagnosis and risk stratification of 214 patients with acute chest pain of < or = 24 h and non-diagnostic or normal ECGs admitted directly to the Cardiac Unit of the Royal Victoria Hospital Belfast from the Mobile Coronary Care Unit or the Accident/Emergency Department. This was a single-centre prospective study, and follow-up (3 months) was complete for all patients. Blood was assessed for quantitative cTnT, cTnI, CKMB mass and myoglobin, and qualitative cTnT on admission and at 12 h. Diagnosis of index event and incidence of new cardiac events (death, non-fatal myocardial infarction, revascularization, or readmission for unstable angina) over 3 months were assessed. Based on standard criteria, myocardial infarction occurred in 37/214 (17%), and unstable angina in 72/214 (34%). At 12 h from admission, cardiac troponins had higher sensitivity for the diagnosis of acute coronary syndromes (myocardial infarction and unstable angina) than conventional markers (cTnI 48%, cTnT 38%, CKMB mass 30% or myoglobin 27%). At 3 months, a new cardiac event had occurred in 42/214 (20%). Significantly higher event rates occurred when any of the biochemical markers was elevated, but the statistical significance was highest for patients with elevated cTnI (p < 0.0001). Whilst gender, history of ischaemic heart disease (IHD), stress test response, cTnT, cTnI, CKMB mass and myoglobin were univariate predictors, cTnI at 12 h and stress test response were the only two independent significant predictors for a subsequent cardiac event at 3 months. Raised cTnI at 12 h after admission had the highest sensitivity for the diagnosis of acute coronary syndromes, and was independently associated with a 2-3 times increased risk of future cardiac events within 3 months among patients with acute chest pain suggestive of myocardial ischaemia but with normal or non-diagnostic ECGs.     

A sensitive method to quantify human cell-free circulating DNA in blood: relevance to myocardial infarction screening

Objectives

Human cell-free circulating DNA (cf-DNA) derived mainly from cell apoptosis and necrosis can be measured by a variety of laboratory techniques, but almost all of these methods require sample preparation. We have developed a branched DNA (bDNA)-based Alu assay for quantifying cf-DNA in myocardial infarction (MI) patients.

Design and methods

A total of 82 individuals were included in the study; 22 MI and 60 normal controls. cf-DNA was quantified using a bDNA-based Alu assay.

Results

cf-DNA was higher in serum compared to plasma and there was a difference between genders. cf-DNA was significantly higher in MI patients compared to the controls. There was no correlation between cf-DNA and creatine kinase-MB (CK-MB), troponin I (cTnI) or myoglobin (MYO). In serial specimens, cf-DNA was sensitive and peaked earlier than cTnI.

Conclusions

The bDNA-based Alu assay is a novel method for quantifying human cf-DNA. Increased cf-DNA in MI patients might complement cTnI, CK-MB and MYO in a multiple marker format.     

Plasma 99th percentile reference limits for cardiac troponin and creatine kinase MB mass for use with European Society of Cardiology/American College of Cardiology consensus recommendations

BACKGROUND: The European Society of Cardiology/American College of Cardiology (ESC/ACC) consensus document for definition of myocardial infarction (MI) is predicated on increased cardiac troponin or creatine kinase (CK) MB mass above the 99th percentile reference limit. The purpose of this study was to determine the plasma (heparin) 99th percentile reference limits for the leading in vitro diagnostic cardiac troponin and CKMB mass assays. METHODS: Blood (heparin plasma) was obtained from healthy adults (n = 696; age range, 18-84 years) stratified by gender and ethnicity. Cardiac troponin I (cTnI) and T (cTnT) and CKMB mass concentrations were measured by eight assays. Reference limits were determined by nonparametric statistical analysis. RESULTS: Two cTnI assays demonstrated at least a 1.2- to 2.5-fold higher 99th percentile for males vs females, with the mean concentrations significantly higher for males (P <0.05). Two cTnI assays also demonstrated a 1.1- to 2.8-fold higher 99th percentile for blacks vs Caucasians, with the mean concentrations significantly higher for blacks (P = 0.05). There was a 13-fold variance between the lowest measured 99th percentile (0.06 microg/L) and the highest (0.8 microg/L). All CKMB assays demonstrated a 1.2- to 2.6-fold higher 99th percentile for males vs females, with mean concentrations significantly higher for males (P <0.0001). Four CKMB assays also showed significantly higher (1.2- to 2.7-fold) mean concentrations for blacks (P <0.02) vs Caucasians. CONCLUSIONS: The heparin-plasma 99th percentile reference limits for cardiac troponin and CKMB mass provide an evidence base in support of the ESC, ACC, and American Heart Association guidelines for detection of myocardial injury. Selective gender and ethnic differences were demonstrated. These data allow clinicians, trialists, and epidemiologists a common point for operational use.     

Health outcomes categorized by current and previous definitions of acute myocardial infarction in an unselected cohort of troponin-naïve emergency department patients

BACKGROUND: In a population originally classified for acute myocardial infarction (AMI) by the World Health Organization (WHO) definition, we compared the health outcomes after retrospectively reclassifying with the European Society of Cardiology and the American College of Cardiology (ESC/ACC) AMI definition, using the peak cardiac troponin I (cTnI) concentrations. The health outcomes were based on the WHO definition and occurred in an era that preceded the use of cardiac troponin biomarkers. METHODS: For 448 patients who presented to the emergency department with symptoms suggestive of cardiac ischemia in 1996, we obtained data for all-cause mortality and recurrent AMI for up to 1 year after the initial presentation. We performed retrospective analysis of the patients' frozen plasma samples to measure cTnI (AccuTnI, Beckman Coulter). RESULTS: At 30, 120, and 360 days, the risk for AMI/death in patients positive for AMI by only the ESC/ACC criteria was significantly lower than the risk in patients positive by both ESC/ACC and WHO criteria, and significantly higher than in patients negative according to both criteria. In a separate analysis, patients with a peak cTnI>0.10 microg/L were at greater risk for AMI/death than patients with cTnI concentrations of 0.04-0.10 microg/L. Patients negative by both definitions or with peak cTnI concentrations<0.04 microg/L had the highest event-free survival rates (92% and 94%, respectively) at 1 year. CONCLUSION: In a troponin-na?ve population, patients classified as positive for AMI by only the ESC/ACC criteria have a prognosis that appears to be intermediate between those classified positive by both the WHO and ESC/ACC definitions and those who meet neither criteria.     

Myoglobin,creatine kinase MB isoforms and creatine kinase MB mass in early diagnosis of myocardial infarction in patients with acute chest pain

OBJECTIVES: Measurements of myoglobin and creatine kinase (CK)-MB isoforms have been suggested to be sensitive tests for the early diagnosis of myocardial infarction (MI). We have investigated the utility of myoglobin, creatine kinase (CK)-MB isoforms and creatine kinase MB mass (CK-MBm) in early diagnosis of MI using cardiac troponin T (cTnT) positivity as a reference. DESIGN AND METHODS: The study population comprised 440 patients who had had chest pain for less than 12 h. Patients were divided into cTnT negative (cTnT-) or cTnT positive (cTnT+) patients (concentration of cTnT >0.1 microg/L at two different time points during 72 h). RESULTS: At the time of admission to the emergency department receiver operating characteristics (ROC) curves of CK-MB isoforms and CK-MBm were not better than that of myoglobin. Six hours after admission CK-MB isoforms and CK-MBm provided statistically significantly larger areas under the curve (AUC) than myoglobin (p < 0.01). When ROC curves were related to the onset of chest pain (< 3 h, 3-6 h, and > 6 h) there were no significant differences between the cardiac markers studied. CONCLUSIONS: According to the present findings, CK-MB isoforms or myoglobin offer no advantage over CK-MBm as early markers of myocardial infarction.     

The sensitivity of cardiac markers stratified by symptom duration

We compared the sensitivity of three commonly used cardiac markers between two subpopulations, those who came to the Emergency Department (ED) late (6–24 h) after their symptoms began, and those who arrived earlier (<6 h), in a prospective comparative trial. Among all adult patients who presented to our ED with symptoms suggestive of acute myocardial infarction (MI), we drew serum for myoglobin, CK-MB, and troponin I upon arrival (time 0) and 2 h later. Outcomes, including acute MI, were determined. Sensitivities for all three markers between the subpopulations who arrived fewer than 6 h from symptom onset were compared to those who arrived later (6–24 h). We enrolled 346 eligible subjects, 36% of whom described cardiac symptoms as beginning 6 or more hours earlier; 14% suffered acute MIs. For time 0, the sensitivity of all three markers for acute MI was significantly higher among those subjects with symptoms of 6 or more hours’ duration as compared to those with less. For troponin I, the increase in sensitivity between these two subpopulations approached 300%. At the time of the 2-h sample, the differences in sensitivities were much less and were not statistically significant. We conclude that cardiac marker values obtained at time 0 among Emergency Department patients who arrive 6 or more hours after cardiac symptom onset provide significantly higher sensitivities as compared to those obtained in patients who arrive earlier. For troponin I, the increase in sensitivity approaches threefold.     

Rapid risk stratification in suspected acute coronary syndrome using serial multiple cardiac biomarkers: A pilot study

Objective: To determine the feasibility of using a biomarker panel of myoglobin, creatinine kinase MB (CK‐MB) and cardiac troponin I (cTnI) to identify patients with suspected acute coronary syndrome (ACS) who are suitable for discharge within 2 h. Methods: We took blood at presentation and at 2 h from patients with suspected ACS and non‐diagnostic electrocardiogram who were admitted to the ED short stay ward for serial electrocardiogram and troponin testing. We used a point‐of‐care device that gives rapid estimation of myoglobin, CK‐MB and cTnI (Triage cardiac panel). These results were compared with the results of our standard hospital cardiac troponin T assay. Patients were followed up by telephone at 30 days. Results: The study group comprised 100 patients (61 men) with mean age of 58 years. Six had a troponin‐positive ACS during their ED stay. One additional patient died of a myocardial infarction within the follow‐up period. The Triage panel at 2 h after presentation predicted 12‐h cardiac troponin T elevation (sensitivity 100%, negative predictive value 99%) and 30‐day events (sensitivity 86%, negative predictive value 97%). The majority of patients were ultimately suitable for discharge. Conclusion: Serial myoglobin, CK‐MB and cTnI have the potential to identify patients who are suitable for early discharge and outpatient work‐up. A large multicentre study is required.     

Diagnostic and prognostic performance of a novel high-sensitivity cardiac troponin T assay compared to a contemporary sensitive cardiac troponin I assay in patients with acute coronary syndrome

Objective

The study sought to compare the clinical performance of two more sensitive cardiac troponin (cTn) assays, a novel high-sensitivity (hs) troponin T assay and a contemporary cTnI assay.

Methods

We measured hs-cTnT (Roche TnThs) and cTnI (Siemens Centaur Ultra) on presentation in 1,384 patients with suspected acute coronary syndrome (ACS) who underwent early invasive strategy within 24?h after presentation. Kaplan–Meier, Cox proportional hazards, and receiver-operating characteristic (ROC) analysis was used to compare their prognostic performance for the prediction of all-cause death and death/MI (myocardial infarction) after a median of 271?days. We also compared the diagnostic performance of these assays on presentation for early diagnosis of non-STEMI.

Results

Both hs-cTnT and cTnI were independently predictive of long-term death (OR 3.51 vs. 2.19) and the composite of death/MI (OR 9.24 vs. 3.61), across the spectrum of ACS and in patients without ACS. When used as a continuous variable, ROC analysis demonstrated significantly higher areas under the curve (AUC) for hs-cTnT as compared to cTnI for the prediction of death/MI (0.721 vs. 0.672, P?=?0.024), a trend to better prediction of all-cause death (0.721 vs. 0.672, P?=?0.093) and significantly higher AUC for early diagnosis of non-STEMI (0.965 vs. 0.901, P?Conclusion Using the 99th percentile cutoff for hs-cTnT and cTnI, both assays enable prediction of adverse long-term outcomes and earlier diagnosis of non-STEMI. Used as a continuous variable, the hs-cTnT assay showed superior performance compared to the cTnI assay, especially in regard to prognosis.     

Validation of NACB and IFCC guidelines for the use of cardiac markers for early diagnosis and risk assessment in patients with acute coronary syndromes

BACKGROUND: International guidelines have been established for the use of cardiac markers in the early diagnosis and risk assessment of patients with acute coronary syndromes. METHODS: A single center, prospective observational study was conducted in a tertiary care university hospital on 200 consecutive patients with suspected acute myocardial infarction (AMI). Blood was drawn on admission and after 2, 4, 8, 12 and 24 h for the measurement of CK-MB/CK activity, myoglobin, CK-MB mass and troponin I. A 6-week follow-up was undertaken for the combined end point of acute coronary syndrome and death. RESULTS: Myoglobin showed an early diagnostic sensitivity of 0.65 on admission, 0.90 after 2 h and 0.92 after 4 h compared with 0.46, 0.74 and 0.88 for CK-MB/CK activity. The combination of myoglobin and cTnI increased the diagnostic value compared with myoglobin alone on admission, 2 and 4 h later. In multivariate analysis, cTnI and CK-MB/CK mass, but not myoglobin and CK-MB/CK activity, were shown to be independent predictors on the 6-week follow-up. CONCLUSIONS: Repetitive myoglobin measurements within 4 h of admission, combined with at least one early troponin test, was shown to be the strategy of choice in early AMI diagnosis and prognosis assessment.     

Serial use of bedside CKMB/myoglobin device to detect acute myocardial infarction in emergency department chest pain patients.

A qualitative bedside device (Spectral Diagnostics, Toronto, Canada) for CKMB and myoglobin (MYOG) detection was evaluated in emergency department (ED) patients with chest pain to determine performance characteristics. At presentation (0 h) and at three hours (3 h), serum was analyzed in the ED with results considered positive if either 0-h or 3-h CKMB or MYOG bands were visible. The results were compared with the diagnosis of myocardial infarction (MI) per hospital discharge diagnosis (n = 132, 87%) or telephone follow-up (n = 19; 1 patient lost to follow-up). Of 151 study patients, 30 (20%) were diagnosed with MI; all were admitted to hospital. On electrocardiogram (EKG), 17 (57%) MI patients had ST-segment elevation. At 0-h, 26 of 30 (87%) MI patients were positive for CKMB/MYOG. By 3 h, 21 of 23 (91%) MI patients were positive for CKMB/MYOG; 7 MI patients were already admitted to hospital. Combining 0-h and 3-h results, the device sensitivity for MI was 93% (28/30) with specificity of 54%. Combining device results plus diagnostic EKG, sensitivity was found to be 100% (30/30). If the device result was positive, then the odds ratio for having an ischemic complication was 6.5. We conclude that the CKMB/MYOG device identified most MI patients at ED presentation and 3 h later. Combining device results with EKG detected all MI patients in the ED.     

Cardiac troponin and beta-type myosin heavy chain concentrations in patients with polymyositis or dermatomyositis

Cardiac troponin T (cTnT), cardiac troponin I (cTnI), myosin heavy chains (MHC), myoglobin, creatine kinase (CK), and creatine kinase isoenzyme MB (CKMB), were measured in blood samples from 39 polymyositis (PM) or dermatomyositis (DM) patients without clinical evidence for cardiac involvement to evaluate their clinical usefulness in this patient population. MHC, myoglobin, and CKMB were frequently elevated and correlated with each other and with disease severity. Undetectable cTnI in all but one patient indicated that MHC was released from skeletal muscle, thereby providing the first laboratory evidence of frequent slow-twitch muscle fibre-necrosis in patients with PM or DM. CKMB was elevated in 51%, cTnT in 41%, and cTnI in only 2.5% of patients. cTnI did not correlate with other markers or with disease severity scores. The close correlations found between cTnT and skeletal muscle damage markers and the relationship between cTnT with disease severity without clinical evidence for myocardial damage suggest a release of cTnT from skeletal muscle. The relationship of cTnT with disease severity indicates a possible role of the marker for risk stratification. However, the prognostic values of cardiac troponins and other muscle damage markers in PM/DM patients remain to be compared in prospective outcome trials.     

Use of the Centaur TnI-Ultra assay for detection of myocardial infarction and adverse events in patients presenting with symptoms suggestive of acute coronary syndrome

BACKGROUND: We determined the diagnostic accuracy of the Advia Centaur TnI-Ultra assay for detecting myocardial infarction (MI) and assessing risk of adverse events in patients presenting with ischemic symptoms suggestive of acute coronary syndrome. METHODS: We measured cardiac troponin I (cTnI) on admission and 6-24 h after admission (follow-up) in plasma specimens from 371 consecutive patients. The end point was the first of cardiac event or death within 60 days. We estimated survival curves using the Kaplan-Meier method and compared groups with the log rank statistic. RESULTS: MI was established in 49 patients (13%). Clinical sensitivities and specificities for MI based on the 99th percentile (0.04 microg/L) were 74% and 84%, respectively, on admission and 94% and 81% at follow-up. ROC curves showed significantly higher accuracy for MI in the follow-up specimen compared with admission (P = 0.001). Overall there were 2 cardiac deaths, 1 noncardiac death, 49 MIs, 7 coronary artery bypass grafts, and 36 percutaneous coronary interventions in 59 patients during follow-up. The event rate in those with cTnI <0.006 microg/L was significantly lower than in groups with cTnI 0.006-0.04 microg/L, >0.04-0.10 microg/L, or >0.10 microg/L (2.8% vs 11.1%, 24.1%, 55.1%, respectively; P <0.0001). Relative risks for the increasing cTnI cutoff groups were 3.9 (95% CI 1.2-13), 8.9 (2.4-34), and 25 (7.3-82) after adjustment for age, diabetes, history of hypertension, previous MI, and estimated glomerular filtration rate. CONCLUSIONS: The TnI-Ultra assay is a sensitive, early diagnostic biomarker for MI and an independent predictor of adverse events at any measurable cTnI in patients with symptoms of acute coronary syndrome.     

Improved assay of cardiac troponin I is more sensitive than other assays of necrosis markers

OBJECTIVE: Highly sensitive and specific assays of cardiac troponins I and T are the preferred biomarkers in diagnosing myocardial infarction (MI). Assays of cardiac troponin I (cTnI) have been improved with the addition of antibodies against the cTnI molecule and may have increased sensitivity. We hypothesized that a cTnI assay with modern antibody configuration will exhibit equal or better sensitivity in the setting of acute MI compared to cTnT and other markers of myocardial necrosis. MATERIAL AND METHODS: We investigated release kinetics of cTnI (Abbott ADV, Abbott Diagnostics), cTnT (Roche Diagnostics), CKMBmass, myoglobin and heart fatty acid binding protein (H-FABP) in 23 patients admitted with acute ST-segment elevation MI undergoing primary percutaneous coronary intervention. Calibrators for the Abbott ADV cTnI assay are traceable to the United States National Institute of Standards and Technology (NIST) reference material for cTnI. Eleven blood samples were drawn from each patient in the period from admission to 24 h. Biomarkers of necrosis showed marked increases in relative concentrations, especially within the first 2 h after admission. RESULTS: From 30 min after admission onwards, cTnI exhibited significantly higher relative concentrations compared to cTnT, CKMBmass, Myoglobin and H-FABP (p<0.05). CONCLUSIONS: The NIST standardized Abbott TnI ADV assay appears to be more sensitive than cTnT and other biomarkers in the early phase of MI.     

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

Objectives

ST-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 methods

856 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 (≤ 4 h from admission) and successful PCI; and 2) cTnI measurements at ED presentation and within 24 h. 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.

Results

A 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 6 h 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 (> 75 years), the cTnI V was significantly increased.

Conclusion

STEMI 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.     

Early diagnosis of acute myocardial infarction. A comparison between chemical predictors

Consecutive patients (n = 155) admitted to coronary care units at three different hospitals were investigated. The overall prevalence of acute myocardial infarction (AMI) was 0.45. The predictive potential with respect to AMI was tested for S-myoglobin, total S-creatine kinase (Tot-CK), and its MB isoenzyme as well as combinations of the different components. S-Myoglobin was determined by latex agglutination (MYO1) and radio-immunoassay (MYO2). The isoenzymes were determined as mass (CKMB1) and catalytic (CKMB2) concentrations. Biochemical tests were performed at arrival and at about 3h, 6h and 12h after the onset of symptoms (chest pain). Diagnostic performance of MYO1 was similar to MYO2 and CKMB2 similar to that of CKMB1. Single components did not show acceptable performance. In the period 6-12 h, combinations of total CK with CK-MB or myoglobin performed equally, with sensitivities of 0.96-0.98 and predictive values of a negative test (PV-) of 0.96-0.98. In view of increasing diagnostic performance for total CK and CKMB following 12 h after the onset of symptoms contrary to a decreasing performance for myoglobin combinations, total CK and CKMB should be used for the early diagnosis of AMI.