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Biomedical subjects

F S Apple

Publications and source records attributed to F S Apple.

At least 19 recordsLinked to original sources
PubMed1999

Implementation of serum cardiac troponin I as marker for detection of acute myocardial infarction.

BACKGROUND: The goal of this prospective study was to assess whether cardiac troponin I (cTnI) could replace creatine kinase (CK)-MB mass as the serum biochemical marker for detection of acute myocardial infarction (AMI). METHODS AND RESULTS: Over a 3-month period, 327 nonselected, consecutive patients were evaluated for AMI with the use of modified World Health Organization criteria including serial electrocardiographs and CK-MB mass determinations at admission and 6, 12, and 24 hours after admission. cTnI measurements were also made at all time points. Sixty-two (19%) patients were diagnosed with AMI. Diagnostic sensitivity and specificity for peak concentrations were equivalent or better for cTnI (100%; 96.3%) compared with CK-MB (88. 2%; 93.2%) and total CK (73.5%; 84.6%), respectively. cTnI demonstrated 100% negative predictive accuracy for ruling out AMI. Further, cTnI maintained a high diagnostic sensitivity (>94%) up to 96 hours after onset of chest pain compared with CK-MB and total CK (both 50% sensitive) in patients with AMI. However, patients with documented Q-wave infarctions had a significantly longer clearance compared with non-Q-wave infarctions (dagger(1/2) 24.2 vs 7.3 hours, respectively; P <.01). There was a significant (P <.02) positive correlation (r = 0.89) between increasing CK-MB mass and increasing cTnI for AMI specimens. CONCLUSIONS: These findings have strongly supported our clinical implementation of cTnI, replacing CK-MB mass as the preferred marker for detection of AMI.

Biomarkers↗
PubMed1999

Simultaneous rapid measurement of whole blood myoglobin, creatine kinase MB, and cardiac troponin I by the triage cardiac panel for detection of myocardial infarction.

This multicenter study evaluated the Biosite Triage(R) Cardiac Panel as a quantitative, multimarker, whole blood system for the detection of acute myocardial infarction (MI). Optimum cutoffs for the discrimination of acute MI (n = 192 patients, 59 with MI) as determined by ROC curve analyses were as follows: 0.4 microgram/L for cardiac troponin I (cTnI); 4.3 microgram/L for the creatine kinase MB isoenzyme (CK-MB); and 107 microgram/L for myoglobin. The Triage Panel showed the following concordances for detection or rule-out of MI compared with established devices: cTnI >89%; CK-MB >81%; myoglobin >69%. No significant differences were present between methods for the same marker. Diagnostic efficiencies demonstrated comparable sensitivities and specificities for the diagnosis of MI in patients presenting with symptoms compared with the Dade, Beckman, and Behring CK-MB, cTnI, and myoglobin assays; the ratio of sensitivity to specificity for each marker was as follows: cTnI, 98%:100%; CK-MB, 95%:91%; myoglobin, 81%:92%. The areas under the ROC curves for the Biosite myoglobin, CK-MB, and cTnI were 0.818, 0.905, and 0.970, respectively; the areas were significantly different, P <0.05. In patients with skeletal muscle injury and renal disease, the Triage cTnI showed 94% and 100% specificity, respectively. The Triage panel offers clinicians a whole blood, point-of-care analysis of multiple cardiac markers that provides excellent clinical sensitivity and specificity for the detection of acute MI.

Creatine Kinase↗
PubMed1999

Multicenter clinical and analytical evaluation of the AxSYM troponin-I immunoassay to assist in the diagnosis of myocardial infarction.

We evaluated the AxSYM troponin I (cTnI) immunoassay for assisting in the detection of acute myocardial infarction (AMI). At four sites, the total imprecision (CV) over 20 days was 6.3-10.2%. The minimum detectable concentration was 0.14 +/- 0.05 microgram/L. Comparison of cTnI measurements between the AxSYM and Stratus (n = 406) over the dynamic range of the AxSYM assay demonstrated good correlation, r = 0.881, with a proportional bias: AxSYM cTnI = 3.50(Stratus cTnI) - 1. 10. The confidence intervals (95%) for the slope and intercept were 3.39-3.64 and -1.32 to -0.95, respectively. The expected cTnI concentration in healthy individuals was </=0.5 microgram/L, whereas the ROC curve-determined cutoff for AMI was 2.0 microgram/L. This gave a diagnostic sensitivity of 91.8% and specificity of 92.4% when tested in serial samples collected within 24 h of admission in 633 patients presenting with chest pain, of which 122 had an AMI. The concordances of the AxSYM cTnI with the Stratus cTnI, OPUS cTnI, and Access cTnI were 95.3%, 95.1%, and 94.3%, respectively, from patients with suspected AMI. The AxSYM cTnI demonstrated excellent clinical specificity, >/=96%, in skeletal muscle injury, chronic renal disease, and same-day noncardiac surgery patients.

Evaluation Studies as Topic↗
PubMed1998

Assessment of left ventricular function using serum cardiac troponin I measurements following myocardial infarction.

The prognosis and extent of injury to the myocardium have previously been assessed by increased serum creatine kinase (CK) MB levels. We report findings from 39 consecutive, acute myocardial infarction (AMI) patients presenting 4.5 h (range, 0.7-12.1 h) after the onset of chest pain. We compared CK MB mass (upper reference limit, 5.0 ng/ml) and cardiac troponin I (cTnI; upper reference limit, 0.8 ng/ml) (Stratus II, Dade International) in serial serum specimens obtained over 36 h after chest pain from AMI patients; within 6 h after onset of chest pain. While the appearance of the kinetics of CK MB and cTnI were similar during the initial 24 h following the onset of chest pain, cTnI was increased significantly (p < 0.05) over CK MB after 9 to 12 h. Half-life determinations (mean+/-S.D.) in 22 of the 39 AMI patients demonstrated a significantly (p < 0.01) shorter half-life in non-Q-wave infarcts [t1/2 6.8 h (+/-5.6)] vs. Q-wave infarcts [t1/2 20.4 h (+/-10.7)]. Further serial time versus marker (mean+/-S.D.) results were significantly correlated (p < 0.001, r = 0.66). Sixteen of twenty patients assessed by echocardiography had an abnormal left ventricular ejection fraction (LVEF); mean 37.6 (S.D. 15.2)%, ranging from 15.4 to 67.6%. LVEF was significantly and inversely correlated to peak CK MB (r = .50, p = 0.03), as well as to peak cTnI (r = 0.46, p = 0.04). Based on these findings, cTnI shows excellent promise as a useful marker of infarct size, for the assessment of left ventricular function, and may potentially replace CK MB as the cardiac-specific marker for AMI detection.

Biomarkers↗
PubMed1998

The use of biochemical markers in ischaemic heart disease: summary of the roundtable and extrapolations.

Acceptable biochemical markers of ischaemic heart disease are now considered to include myoglobin, CK-MB isoforms, CK-MB, and cardiac troponins T and I. AST (SGOT), total LD and LD isoenzymes, and total CK activity measurements are regarded as obsolete for this purpose. All acceptable biochemical markers must be available, if required, with a turnaround time of < 20 min. Such a service can either be provided by quantitative assays in a well-equipped laboratory or by qualitative point-of-care (bedside) devices (except for the CK-MB isoform assay) which can also be used in patients' homes and ambulances. There is, however, a pressing need for the careful side-by-side assessment of the relative merits of each of these biochemical markers to permit definitive conclusions about their future usage. A particular problem is the lack of primary standards for CK-MB and troponin I assays. The sensitivity of the initial ECG is about 50% for detecting myocardial damage; thus the use of biochemical markers may contribute to the early diagnosis and monitoring of thrombolytic therapy and these possible applications are examined. In addition, biochemical markers are presently the gold standard for the diagnosis of minor myocardial damage. There is now good evidence that biochemical markers, particularly the cardiac troponins, have a prognostic function in ischaemic heart disease although such findings pose unanswered clinical management questions. At the same time, it is recognized that there is often no need at all for the use of any biochemical marker when the clinical diagnosis is unequivocal, other than for prognosis, monitoring thrombolytic therapy, or diagnosing reinfarction.

Biomarkers↗
PubMed1998

Cardiac troponin I and T alterations in dog hearts with myocardial infarction: correlation with infarct size.

We studied the distribution of cardiac troponins I (cTnI) and T (cTnT) in ischemic left ventricular (LV) tissue in 7 infarct zones, 7 remote nonischemic LV areas, and 7 nonischemic areas each from the right ventricle and circumflex in an acute coronary artery occlusion dog model to correlate myocardial loss of troponins with infarct size 3 weeks after the infarction and to determine whether the decrease of troponins in ischemic myocardium can be used to assess the infarct size in dogs after coronary occlusion. The serum profiles for time vs mean cTnI and cTnT concentrations in 6 dogs after occlusion showed peak concentrations at 1 day and 5 days, respectively. The concentrations of troponins were similar in all nonischemic zones. However, cTnI and cTnT decreased significantly in the LV ischemic tissues. Loss of cTnT, but not cTnI, in ischemic LV tissues correlated significantly with infarct size 3 weeks after the infarction. Biochemical alterations suggest that the increases in serum troponins after the infarction parallel the decreases in tissue concentrations of troponins.

Animals↗
PubMed1998

Cardiac troponin I measurement with the ACCESS immunoassay system: analytical and clinical performance characteristics.

We evaluated the ACCESS cardiac troponin I (cTnI) immunoassay as a marker for myocardial infarction (MI). Total imprecision was 6.0% to 13.5%, the minimum detectable concentration was 0.007 microg/L, and the limit of quantitation was 0.046 microg/L. Comparison of cTnI measurement between the ACCESS and Stratus systems (n = 114) showed a proportional difference: ACCESS cTnI = 0.0996 Stratus cTnI + 0.049 microg/L (r = 0.811). Fifty-nine of 61 ambulatory patients without cardiac symptoms had no detectable cTnI (95% range, 0.00 to 0.025 microg/L). The optimum cutoff for discriminating MI (n = 289, 45 with MI) was 0.15 microg/L by receiver operator characteristic curve analysis; at this cutoff, the ACCESS cTnI assay showed a sensitivity of 88.9% (95% CI, 79.7-98.1%) and specificity of 91.8% (95% CI, 88.4-95.2%). The ACCESS cTnI assay results showed 89.4% and 93.0% concordance with the MB isoenzyme of creatine kinase (CK-MB) mass and Stratus cTnI results, respectively, for classification of patients with suspected MI. The ACCESS cTnI assay appears to show sensitivity and specificity comparable with those of both CK-MB mass and Stratus cTnI assays for the diagnosis of MI in patients presenting within 12 h of onset of symptoms.

Adult↗
PubMed1998

Characterization of cardiac troponin subunit release into serum after acute myocardial infarction and comparison of assays for troponin T and I. American Association for Clinical Chemistry Subcommittee on cTnI Standardization.

We examined the release of cardiac troponin T (cTnT) and I (cTnI) into the blood of patients after acute myocardial infarction (AMI). Three postAMI serum samples were applied in separate analytical runs onto a calibrated gel filtration column (Sephacryl S-200), and the proteins were separated by molecular weight. Using commercial cTnT and cTnI assays measured on collected fractions, we found that troponin was released into blood as a ternary complex of cTnT-I-C, a binary complex of cTnI-C, and free cTnT, with no free cTnI within the limits of the analytical methodologies. The serum samples were also examined after incubation with EDTA and heparin. EDTA broke up troponin complexes into individual subunits, whereas heparin had no effect on the assays tested. We added free cTnC subunits to 24 AMI serum samples and found no marked increase in the total cTnI concentrations, using an immunoassay that gave higher values for the cTnI-C complex than free cTnI. To characterize the cross-reactivity of cTnT and cTnI assays, purified troponin standards in nine different forms were prepared, added to serum and plasma pools, and tested in nine quantitative commercial and pre-market assays for cTnI and one approved assay for cTnT. All nine cTnI assays recognized each of the troponin I forms (complexed and free). In five of these assays, the relative responses for cTnI were nearly equimolar. For the remainder, the response was substantially greater for complexed cTnI than for free cTnI. Moreover, there was a substantial difference in the absolute concentration of results between cTnI assays. The commercial cTnT assay recognized binary and ternary complexes of troponin on a near equimolar basis. We conclude that all assays are useful for detection of cardiac injury. However, there are differences in absolute cTnI results due to a lack of mass standardization and heterogeneity in the cross-reactivities of antibodies to various troponin I forms.

Biomarkers↗
PubMed1998

Cardiac troponin T isoforms expressed in renal diseased skeletal muscle will not cause false-positive results by the second generation cardiac troponin T assay by Boehringer Mannheim.

The purpose of this study was to determine whether the two monoclonal anti-cardiac troponin T (cTnT) antibodies (MAbs) used in the second generation cTnT assay by Boehringer Mannheim (BM, capture Ab, M11.7; detection Ab, M7) would detect cTnT isoforms expressed in human skeletal muscle in response to chronic renal disease (CRD). cTnT expression was examined in skeletal muscle biopsies obtained from 45 CRD patients, as well as nondiseased human heart (n = 3) and skeletal muscle (n = 3). cTnT proteins were resolved by modified 7.5% sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to nitrocellulose, and probed with the following anti-cTnT MAbs: M11.7; M7; JS-2, Lakeland Biomedical; and 13-11, Duke University. All four antibodies detected the cTnT isoforms (Ta, Te) expressed in human myocardium. In 20 of 45 skeletal muscle biopsies, MAb M11.7 recognized its epitope in one to three proteins, molecular mass 34-36 kDa, designated Te, Td, and Tc; the strongest signal was that of Te. The same proteins were recognized by MAbs JS-2 and 13-11. The BM M7 antibody did not detect the cTnT isoforms in the molecular mass range of 34-36 kDa. However, MAb M7 did detect a cTnT isoform, molecular mass 39 kDa, in 2 of 45 biopsies. This isoform had an electrophoretic mobility similar to the predominant heart cTnT isoform, Ta. We conclude that cTnT isoforms are expressed in the skeletal muscle of CRD patients. However, given the epitopes recognized by the BM MAbs M7 and M11.7 and the variable presence of these cTnT isoforms in skeletal muscle, the second generation BM cTnT assay will not detect these isoforms if they are released from skeletal muscle into the circulation.

Adult↗
PubMed1998

Expression of cardiac troponin T isoforms in skeletal muscle of renal disease patients will not cause false-positive serum results by the second generation cardiac troponin T assay.

The purpose of this study was to determine whether the two monoclonal anti-cardiac troponin T (cTnT) antibodies used in the second generation cTnT assay (capture Ab, M11.7; detection Ab, M7) would detect expression of cTnT isoforms in skeletal muscle from chronic renal disease patients. Skeletal muscle biopsies obtained from 45 chronic renal disease patients (as well as human heart muscles and normal human skeletal muscles) were prepared for Western blot analysis and blotted with the following anti-cTnT antibodies: M 11.7; M7; JS-2, Lakeland Biomedical; 13-11, Duke University) and anti-cTnI antibody JS-1. Using the M11.7 Ab, 20 of 45 renal skeletal muscles demonstrated one to three cTnT isoforms, MW34 39 kDa. These findings were confirmed by both the Lakeland and Duke antibodies. However the BM M7 antibody detected, in two of 45 muscles, only a protein with a MW of approximately 39 kDa. All four antibodies demonstrated equivalence in detection the 39 kDa cTnT isoform expressed in heart muscle. None detected any isoforms in normal skeletal muscle. A single cTnI isoform, MW 25 kDa, was detected by JS-1 only in normal adult myocardium. Based on the antibody configuration of the second generation cTnT assay, we conclude that while cTnT isoforms are expressed in human skeletal muscle obtained from chronic renal disease patients, if released into the circulation, they would not be detected.

Adult↗
PubMed1997

Prognostic value of serum cardiac troponin I and T in chronic dialysis patients: a 1-year outcomes analysis.

To determine the incidence and prognostic value of increased serum cardiac troponin I and T concentrations over 12 months in chronic hemodialysis patients, we performed a retrospective chart review in 16 patients undergoing chronic renal hemodialysis randomly selected from the Regional Kidney Disease Program without prior knowledge of their cardiac status. Serum markers of myocardial injury (cardiac troponin I [cTnI], cardiac troponin T [cTnT], and creatine kinase MB [CK-MB]) were measured and clinical outcomes were assessed. At the beginning of the study, 12 of 16 (75%) patients had increased serum enzyme-linked immunosorbent assay (ELISA) cTnT concentrations greater than 0.20 micrograms/L, eight (50%) had increased serum CK-MB greater than 5.0 micrograms/L, and three (19%) had an increased cTnI greater than 0.8 micrograms/L. Over the 1-year study period, the cardiac event rate (n = 4 with fatal myocardial infarction) was correlated to the patients who displayed the higher elevations of cTnT, CK-MB, and cTnI. In the remaining 12 patients studied at the end of 1 year, seven (58%) had increased ELISA cTnT levels and five (42%) had increased CK-MB levels; no patients had elevated cTnI levels. Reanalysis of ELISA cTnT values with a newly formulated Enzymun cTnT assay showed no significant differences. Our data suggest that whereas substantial increases in cardiac markers tended to have a poor prognostic outcome, there was a high incidence of increased cTnT and CK-MB concentrations without evidence of myocardial injury in chronic hemodialysis patients. The lack of absolute cardiospecificity of cTnT and CK-MB may prove cTnI to be the desired serum marker for the detection of myocardial injury in patients with chronic renal disease.

Adult↗
PubMed1997

Early diagnostic efficiency of cardiac troponin I and Troponin T for acute myocardial infarction.

OBJECTIVE: To compare the early diagnostic efficiency of the cardiac troponin I (cTn-I) level with that of the cardiac troponin T (cTn-T) level, as well as the creatine kinase (CK), CK-MB, and myoglobin levels, for acute myocardial infarction (AMI) in patients without an initially diagnostic ECG presenting to the ED within 24 hours of the onset of their symptoms. METHODS: A prospective, observational, cohort study was performed involving chest pain patients admitted to a large urban community hospital. Participants were consecutive consenting ED chest pain patients > or = 30 years of age. Exclusions included duration of symptoms > 24 hours, inability to complete data collection, receipt of CPR, and ST-segment elevation on the initial ECG. Measurements included levels of cTn-I, cTn-T, CK, CK-MB, and myoglobin at the time of presentation and 1, 2, 6, and 12-24 hours after presentation as well as presenting ECG and clinical follow-up. Confirmation of the diagnosis of AMI was based on World Health Organization criteria. RESULTS: Of the 177 patients included in the study, 27 (15%) were diagnosed as having AMIs. The sensitivities of all 5 biochemical markers for AMI were poor at the time of ED presentation (3.7-33.3%) but rose significantly over the study period. The sensitivity of cTn-T was significantly better than that of cTn-I over the initial 2 hours, but both markers' sensitivities were low (< 60%) during this time frame. The cTn-I was significantly more specific for AMI than was the cTn-T, but not significantly better than CK-MB or myoglobin. Likelihood ratio analysis showed that the biochemical markers with the highest positive likelihood ratios for AMI during the first 2 hours following ED presentation were myoglobin and CK-MB. From 6 through 24 hours, the positive likelihood ratios for cTn-I, CK-MB, and myoglobin were superior to those of CK and cTn-T. CONCLUSIONS: cTn-I, CK-MB, and myoglobin are significantly more specific for AMI than are CK and cTn-T. Myoglobin is the biochemical marker having the highest combination of sensitivity, specificity, and negative predictive value for AMI within 2 hours of ED presentation. Neither cTn-I nor cTn-T offers significant advantages over myoglobin and CK-MB in the early (< or = 2 hours) initial screening for AMI. The cardiac troponins are of benefit in identifying AMI > or = 6 hours after presentation.

Biomarkers↗
PubMed1997

Cardiac troponin T composition in normal and regenerating human skeletal muscle.

Cardiac troponin T (cTnT), measurement of which has been recommended for diagnosing myocardial infarction, was initially believed to be specific for the heart. However, recent publications have reported cTnT in sera of patients without cardiac disease; therefore, we investigated whether cTnT could be found in human skeletal muscle tissues. Using immunohistochemistry, Western blot, and quantitative cTnT ELISA, we assayed human heart (n = 3), normal human skeletal muscle (n = 6), and diseased skeletal muscle samples from patients with polymyositis (PM, n = 13) and Duchenne muscular dystrophy (DMD, n = 6). All heart specimens contained cTnT, but the expression of cTnT in normal skeletal muscle samples varied widely, ranging from no expression (quadriceps femoris) to expression by up to 20% of the muscle fibers (diaphragm). Immunohistochemistry detected cTnT in skeletal muscle of 8 of the PM patients and all of the DMD patients. Mean myofibrillar cTnT concentrations (mg/g myofibrillar protein) were: cardiac = 10.0, normal skeletal = 0.8, PM skeletal = 0.7, and DMD skeletal = 4.37, confirming the results of immunohistochemistry. Western blot analysis also confirmed the expression of cTnT in muscle from DMD patients. These findings provide evidence that cTnT is not 100% cardiac-specific but also is expressed in regenerating (PM and DMD) as well as in normal (nonregenerating) skeletal muscle.

Antibody Specificity↗