Assay performance improved, but which "scorecard" designation for Vitros Troponin I?

BACKGROUND: Since cardiac troponins assay technology should comply with the recommendations of scientific societies (i.e. imprecision (10%) at the 99th percentile value observed in healthy subjects being the analytical qualifying aspect), the aim of the present study was to evaluate whether an improved troponin assay (Vitros Troponin I ES) provides data that meet the "guideline acceptable"criteria recently defined in a proposed scorecard. METHODS: Vitros Troponin I ES, an enhanced chemiluminescence immunoassay, was evaluated in a multicenter study considering: limit of blank (LOB, 60 replicates of 0 calibrators), limit of detection (LOD, 12 measurements for each of 5 serum pools), precision, linearity using control materials and serum plasma pool; matrix samples study matching serum and lithium-heparin plasma (n=107 hospitalized patients); the 99th percentile limit in serum samples from 500 healthy Caucasian donors. RESULTS: LOB and LOD, 0.0029 µg/L and 0.0030 µg/L respectively; coefficients of variation (total CV%), obtained by running 3 levels of control materials and 10 serum pools, from 15.2% (x(-)=0.014 µg/L) to 2.0% (x(-)=5.324 µg/L); method, linear up to 70 µg/L. No significant differences were found between serum and lithium-heparin matched sample (p=0.48) values; 99th percentile limit of cTnI distribution in healthy donors, 0.021 µg/L. CONCLUSION: Since its analytical reliability meets the proposed performance and scorecard requirements, the Vitros TropI method can be considered "contemporary" and "guideline acceptable".

Continuous retrograde warm blood reperfusion reduces cardiac troponin I release after heart transplantation: a prospective randomized study.

During heart surgery, cardiac troponin I (cTn-I) measurement provides a tool to evaluate different cardioprotective techniques. To investigate myocardial protection during heart transplantation (HTx), cTn-I and creatine kinase (CK)-MB release was measured in 42 patients randomized to receving either continuous retrograde warm blood reperfusion or no reperfusion after cold cardioplegia. A significant linear correlation was found between donor heart ischemic time and peaks and the area under the curve of cTn-I and CK-MB release. In patients with an ischemic time longer than 90 min, cTn-I release was significantly lower in those receiving continuous retrograde warm cardioplegia than in controls. No significant difference was observed for CK-MB, tCK, and myoglobin. Our data suggest that the measurement of postoperative cTn-I release may provide a method to evaluate ischemic cardiac damage after HTx. When the ischemic time is longer than 90 min, warm retrograde blood cardioplegia provides better myocardial protection than no reperfusion.

Multicenter evaluation of five assays for myoglobin determination.

BACKGROUND: Lacking assay standardization, different myoglobin methods may produce results that differ significantly. METHODS: A multicenter study was carried out to compare the analytical performance of five commercially available assays for myoglobin measurement. Linearity, imprecision, interferences, and method comparison were studied according to NCCLS guidelines, whereas reference values were determined following IFCC recommendations. RESULTS: The BNA and Opus showed relatively high imprecision (all but one total CV >7.4%). Other assays showed lower CVs, but they varied among laboratories, particularly at a normal myoglobin concentration (Access, 6.0-11%; Hitachi, 3.8-5.8%; Stratus, 3.4-6.5%). Results were lower in anticoagulated samples on the Access, in heparin and citrate samples on the Stratus, and in citrate samples on the BNA and Opus, and increased in heparin and EDTA samples on the Hitachi. Use of separator gel produced results significantly lower (P <0.001) on the Hitachi and higher (P = 0.016) on the Opus. Bilirubin, turbidity, and hemoglobin had no effect on evaluated methods, but rheumatoid factor affected the Access. In method comparisons, high correlation coefficients (>/=0.98) were obtained. The Stratus gave higher results; however, the Access and BNA gave the lowest. The following upper reference limits (microgram/L) for men and women, respectively, were obtained: Access, 70 and 52; BNA, 51 and 49; Hitachi, 67 and 58; Opus, 80 and 50; and Stratus, 86 and 63. CONCLUSION: The possibility of high imprecision and marked disagreement among commercial myoglobin assays should be carefully considered in clinical practice.

Soluble E-selectin is not a marker of unstable coronary plaque in serum of patients with ischemic heart disease.

Increased level of soluble cell adhesion molecules may be a marker for atherosclerosis and/or reflect complication of the atherosclerotic plaque. To test whether expression of cell adhesion molecules is more pronounced in unstable versus stable coronary plaques, we measured the serum level of soluble E-selectin (sE-selectin) in 99 consecutive patients admitted to the hospital for acute coronary syndromes (ACS) and in 61 patients with chronic coronary artery disease (CAD) using a commercially available ELISA kit. We also measured the sE-selectin concentration in 20 sex- and age-matched subjects without clinical evidence of atherosclerosis, who served as controls. The mean sE-selectin level was higher in both groups of patients compared with controls (ACS, 35.0 +/- 23.4 ng/mL; chronic CAD, 32.9 +/- 21.0 ng/mL; controls, 14.5 +/- 6.6 ng/mL; one-way ANOVA, P = 0.001), but there was no difference between patients with ACS and chronic CAD. Furthermore, there was a trend (P = 0.08) toward a decrease in sE-selectin with an increase in the extent and severity of CAD. In patients with ACS, the in-hospital cardiac event rate was 8%. Although mean sE-selectin concentration tended to be higher in patients with (49.2 +/- 42.1 ng/mL) than in those without (33.8 +/- 21.3 ng/mL) in-hospital cardiac events, the difference was not significant. In 53 patients with ACS, C-reactive protein was measured and showed no correlation with the sE-selectin concentration. These findings show that although sE-selectin concentration is elevated in the presence of clinically relevant atherosclerosis, it does not further increase during the unstable phase of the disease, indicating that sE-selectin is not a reliable indicator of a complicated atherosclerotic plaque.

Troponin I as a specific marker for heart damage after heart transplantation in a patient with becker type muscular dystrophy.

In a patient with Becker type muscular dystrophy, the development of cardiomyopathy may require heart transplantation, and during both the perioperative period and later it is useful to determine whether myocardial cell damage is occurring; however, the measurement of serum levels of creatine kinase (CK), MB isoenzyme, is not useful because that isoenzyme is released by the dystrophic skeletal muscle, as well as damaged myocardium. Because cardiac troponin I (cTn I) seems to be quite specific for myocardial cells, we reasoned that measurement of serum levels of this protein could distinguish between myocardial damage and skeletal muscle disease in this patient during and after transplantation. During the immediate postoperative period, the time course of the release of total CK (tCK), CK MB mass, myoglobin, and cTn I were different, yielding a peak within 4 hours for CK MB, 24 hours for myoglobin and 36 hours for tCK and cTn I. During the first postoperative year, the patient displayed a release of tCK, CK MB, and myoglobin; cTn I was constantly lower than the reference value for cardiac myocyte necrosis, suggesting the presence of a continuous muscular damage without any myocardial involvement and an accurate specificity of cTn I to differentiate between myocardial and muscular cell damage in patients with neuromuscular disorders.

[Cardiac troponin I and T in unstable angina: incidence, correlation, kinetics of release and prognostic value]. / Troponina i cardiaca e troponina T cardiaca nell'angina instabile: incidenza, correlazione, cinetica di rilasciamento e valore prognostico.

BACKGROUND: The aim of this study was to ascertain the incidence of altered serum cardiac Troponin-T (cTnT) and cardiac Troponin I (cTnI) in patients with unstable angina, the concordance between findings for the two proteins, their release kinetics and their utility in predicting coronary events. METHODS: We studied 32 consecutive patients (pts) admitted to the Coronary Unit with a diagnosis of unstable angina; following Braunwald classification criteria, 5 pts were in class I, 4 class II, 23 class III. A blood sample was taken on admission to hospital and subsequently every 8 hours for two days, a total of 7 samples being obtained per pt. Cardiac-TnT values ranging from 0-0.17 mugr/L (Boehringer Mannheim) were considered normal, as were cTnI values ranging from 0 to 0.7 mugr/L (Stratus-Dade). RESULTS: Among 218 samples, altered cTnT values (0.18-0.68 mugr/L) were found in 19 (3 pts), and 13 of these samples were positive for cTnI (0.8-5.5 mugr/L), while the remaining 6 showed borderline values for cTnI (0.5-0.7 mugr/L). No cTnT negative samples were found to be positive for cTnI. The release kinetics of cTnT and cTnI were comparable in all three cases, with a "plateau" pattern, unlike the kinetics in the course of acute myocardial infarction (AMI). The mean follow-up was 13 months on average (range 1-19). In two pts with altered cTnT and cTnI values, symptoms were controlled with medical therapy, while the remaining patient failed to respond to medical therapy and therefore underwent PTCA. Fifteen months later, they are alive and have not had myocardial infarction. Of the 29 pts with normal cTnT and cTnI values, three developed AMI, which in two cases was fatal. Seven pts were submitted PTCA, seven to aorto-coronary bypass surgery, two were subsequently rehospitalized for a recurrent angina symptoms. In 13 pts complete control of symptoms was achieved with medical therapy. CONCLUSIONS: Our findings demonstrate that the incidence of altered cTnT and cTnI values in pts with unstable angina is low; there is close agreement between findings for the two proteins; in cases of angina, the cTnT and cTnI release kinetics are different from those in AMI. The finding of altered cTnT and cTnI values in the serum of our pts with unstable angina does not appear to be of prognostic value for future coronary events.

[Cardiac troponin I in unstable angina]. / La troponina I cardiaca nell'angina instabile.

BACKGROUND: Unstable angina implies high risk of myocardial infarction and sudden death. Increased levels of cytoplasmatic enzymes and proteins (creatine phosphokinase, MB creatine phosphokinase troponin T, etc.) were described in unstable angina, providing information about incoming major coronary events. Cardiac troponin I (cTn-I) is a structural protein inhibiting the actinomyosine ATPase; it is only found in myocardial cells. Serum titration of cTn-I has been recently introduced into clinical practice as a sensitive and specific marker of myocardial cellular necrosis. OBJECTIVES: The aim of our prospective study was to assess the presence of cTn-I in blood samples of patients with unstable angina and no signs of myocardial necrosis. Furthermore we intended to test the possible use of cTn-I in unstable angina as a prognostic marker of major coronary events on short and middle term. METHODS: We studied 33 consecutive patients admitted to our CCU for unstable angina. According to unstable angina Braunwald's classification, 6 patients were included in the first class, 4 patients in the second class and 23 patients in the third class. We excluded patients with acute or recent myocardial infarction. Blood samples of all patients were obtained at the time of CCU admission and every eight hours in the first and second day. Serum cTn-I titration was performed with the sandwich immunoenzymometric method, recently introduced by Diagnostic Pasteur. Two months follow-up was carried out in order to survey major coronary events and revascularization procedures, either angioplasty or coronary artery bypass surgery. RESULTS: No patients with unstable angina exhibited cTn-I in their blood samples; accordingly, cTn-I was not found in the first blood sample of a patient who underwent myocardial infarction during hospitalization. During the follow-up 2 patients died of myocardial infarction, 9 patients had surgical revascularization and 5 patients angioplasty. CONCLUSIONS: CTn-I is a sensitive and specific marker of myocardial necrosis. It is not found in patients with unstable angina; therefore it has no role as a prognostic marker of major coronary events.

Transient hyperphosphatasemia of infancy and childhood. A study of serum alkaline phosphatase by electrofocusing techniques.

OBJECTIVE: To evaluate serum alkaline phosphatase (ALP) isoenzymes, using a sensitive electrofocusing technique, in transient hyperphosphatasemia of infancy and childhood. DESIGN: Randomized study of infants and children who provided serum samples when an unusual magnitude of total ALP activity was noted. SETTING: Reference enzyme laboratories in Gorizia and Bergamo (Italy) and in Charleston, SC (USA). PATIENTS: A total of 135 infants and children noted to have markedly increased total ALP activity. MAIN OUTCOME MEASURES: Recognition of the disease pathogenesis with appropriate treatment instituted. RESULTS: Three groups of patients were identified: (1) previously healthy patients who showed additional laboratory evidence of viral and protozoal infection, in whom the ALP isoenzyme pattern reflected the primary target organ(s) of the infection; (2) patients with clinical evidence of failure to thrive due to preexisting disease, along with a superimposed infection (the ALP isoenzyme pattern reflected the specific infection and fractions associated with the primary disease); and (3) patients exhibiting failure to thrive (nonorganic or caloric deficit) who did not show evidence of infection. The total ALP in the third group was lower than in the other groups, was of hepatic and bone origin, and decreased when a positive caloric balance was established. CONCLUSION: We examined several mechanisms to explain the hyperphosphatasemia. A perplexing question remains: Will a small group of infants and children respond to infection with this magnitude of ALP activity? Conversely, do all children respond, but a small number fortuitously undergo laboratory measurements that include ALP levels?

Interferon alfa-2a therapy in cryoglobulinemia associated with hepatitis C virus.

BACKGROUND: Essential mixed cryoglobulinemia is frequently associated with hepatitis C virus (HCV) infection. A beneficial effect of interferon alfa therapy has been reported, but we do not know whether the antiviral activity of the drug affects the clinical and biochemical manifestations of disease. METHODS: In a prospective randomized, controlled trial, we studied 53 patients with HCV-associated type II cryoglobulinemia. A group of 27 patients received recombinant interferon alfa-2a thrice weekly at a dose of 1.5 million units for a week and then 3 million units thrice weekly for the following 23 weeks. The 26 control patients did not receive anything apart from previously prescribed treatments. All patients were then followed for an additional 24 to 48 weeks. RESULTS: Interferon was usually well tolerated, but it was permanently discontinued in two patients because of atrial fibrillation and depression. Two of the 26 patients in the control group were lost to follow-up. After the treatment period, serum HCV RNA was undetectable in 15 of the remaining 25 patients who received interferon alfa-2a, but in none of the controls. In comparison with the control group, the 15 patients with undetectable levels of HCV RNA in serum had significant improvement in cutaneous vasculitis (P = 0.04) and significant decreases in serum levels of anti-HCV-antibody activity (P = 0.007), cryoglobulins (P = 0.002), IgM (P = 0.002), rheumatoid factor (P = 0.001), and creatinine (P = 0.006). After treatment with interferon alfa-2a was discontinued, viremia and cryoglobulinemia recurred in all 15 HCV RNA-negative patients. On resumption of treatment, three of four patients had a virologic, clinical, and biochemical response. CONCLUSIONS: The therapeutic efficacy of interferon alfa-2a in HCV-associated cryoglobulinemia is closely related to its antiviral activity, thus supporting the idea that HCV infection may be a cause of this disease.