Search

Background: Several studies have investigated changes in circulating hormones and markers of cardiac status after heart transplantation in humans. As a result, plasma levels of various hormones and autocoids have been associated with cardiac allograft rejection status. However, no clear associations can be defined given the highly contradictory nature of the available literature., Methods: In this study of 69 consecutive heart transplant patients followed for >2 years we examine the relationship between neurohumors potentially related to allograft rejection and endomyocardial biopsy grade of rejection (according to the ISHLT) and hemodynamic status. Markers assessed include brain natriuretic peptide (BNP), amino-terminal pro-BNP (N-BNP), atrial natriuretic factor (ANF), adrenomedullin, interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, troponin C and C-reactive protein., Results: The highest plasma levels for most neurohumors were found shortly after surgery and showed a trend towards normalization with time. BNP and N-BNP were the only significantly elevated plasma analytes for patients with Grade 3 rejection as compared with other ISHLT grades. ANF plasma levels correlated with BNP and N-BNP in Grades 0 to 2, but not in Grade 3, suggesting that in this rejection grade the usual coordinated changes observed in BNP and ANF secretion no longer exist. Cardiac filling pressures were correlated with plasma BNP, N-BNP and ANF levels only for Grades 0 and 1., Conclusions: The timing of blood sampling after transplantation influences the level of the neurohumors measured, which may help explain the conflicting literature reports on the association between neurohumor levels and rejection grade. The significant increase in circulating levels of BNP and N-BNP observed in most cases of Grade 3 rejection occurred with no apparent relationship to post-transplantation time, which suggests a specific influence of acute rejection on BNP gene expression.

Many assays 1(st), 2(nd) even 3(rd) generation are at present available to determine the concentration of cardiac troponin I and T. With the redefinition of upper reference value in the acute coronary syndromes, the aim of this study was to evaluate the clinical and analytical performance of 2 troponins assays: Troponin Ic 2(nd) generation (AccuTnI) on Access 2 of Beckman Coulter and Troponin Tc 3(rd)generation (Troponin T STAT) on Elecsys 2010 of Roche Diagnostics. The analytical performance observed with these 2 assays are accurate (analytical and functional sensitivity, repetability and reproductibility). Comparing each method with Dade Behring assay (Flex Troponine-I Cardiaque, TROP) on Dimension RxL, the correlation observed with AccuTnI kit on Access 2 can be put into the equation: AccuTnI = 1.08 (TnIc TROP) - 0.34, r = 0.99. On the contrary, it's more difficult to compare cTnI and cTnT. The study of decisonnal values indicated by Beckman Coulter for cTnI (0.04 microg/L at the 99 degrees percentil, 0.06 microg/L for a CV < or =10%) show a better specificity (76%) and predictive positive value (89%) with a sensitivity at 100% at 0.1 microg/L, fixed and used in the laboratory for its better agreement between sensibility / specificity and its imprecision below 10 %. For the cTnT values published by Roche Diagnostics (0.01 microg/L), at the 99 degrees percentil and 0.03 microg/L for a CV < or = 10%, the specificity is lower, so the decisionnal value 0.1 microg/L seems to be more suitable. During this study, few false positive and negative cTnT values have been observed, in patients with complex pathologies; this eventuality must be taken in consideration if clinical findings are not in good accordance with laboratory results.

Background: Elevated concentrations of cardiac biomarkers, such as troponins and natriuretic peptides, have been shown to be predictive of poorer long-term cardiovascular outcomes in stable patients with end-stage renal disease (ESRD). However, little is known about the relationship between elevated concentrations of these cardiac markers and underlying coronary artery pathology in these patients. The aim of the present study was to investigate associations between coronary artery calcification (CAC) and the concentrations of cardiac biomarkers in ESRD patients., Methods: We conducted a cross-sectional study of 38 asymptomatic patients (median age, 54 years; 26 males, 12 females; diabetic, 39%) who were undergoing chronic haemodialysis. In these patients, pre-dialysis circulating concentrations of cardiac troponin T (cTnT), cardiac troponin I (cTnI), creatine kinase-MB (CK-MB) and B-type natriuretic peptide (BNP) were measured. We quantified the level of CAC by multirow spiral computed tomography to obtain a CAC score. CAC scores > or = 400 were defined as being indicative of severe CAC., Results: Severe CAC was detected in 17 patients (45%). The degree of CAC severity was positively associated (P < 0.05) with cTnT concentrations. Thus, 15% of patients had severe CAC in the lowest tertile of cTnT, 50% had severe CAC in the middle third, and 69% in the highest third. Similarly, the degree of severity of CAC was positively associated (P < 0.01) with cTnI concentrations across concentration categories. In contrast, there was no association between the degree of CAC severity and the concentrations of either BNP or CK-MB. A logistic regression analysis revealed that elevated concentrations of cTnT (> or = median vs or = 0.1 ng/ml vs

Purpose of the Review: Elevated levels of cardiac troponins, indicative of the presence of cardiac injury, have been reported in critically ill patients. In this review, the incidence, significance, and clinical relevance of elevated troponin levels among this group of patients will be discussed., Recent Findings: It has been shown that elevated cardiac troponin levels can be present among critically ill septic patients without evidence of myocardial ischemia. Recent studies show that elevated troponin levels are also present in a diverse group of critically ill patients without sepsis or septic shock. In addition, several but not all studies show that the mortality rate of troponin-positive patients is significantly higher compared with troponin-negative patients., Summary: Elevated troponin levels are not only present in patients suffering from acute coronary syndromes but can also be present in critically ill patients. Even minor elevations are specific for myocardial injury. However, every elevated troponin level in the critically ill patient should not be rigorously diagnosed or treated as a myocardial infarction., (Copyright 2004 Lippincott Williams & Wilkins)

Objectives: We recently reported on the occurrence of a common interfering factor (IF) that negatively affects determinations of cardiac troponin I (cTnI). The aim of the present investigation was to extend our initial finding by a detailed epitope-based determination of the location of IF and to reveal the approximate size and characteristics of IF., Design and Methods: Two-site immunoassays using combinations of 16 monoclonal and 2 polyclonal cTnI antibodies and 1 monoclonal troponin C (TnC) antibody were used to measure the analytical recovery of cTnI or cTnI-TnC in serum samples. Gel filtration of serum samples containing IF was performed and the analytical recovery of cTnI in the fractions was determined. EDTA-plasma samples to which cTnI had been added and serum samples containing endogenous cTnI were also separated by gel filtration., Results: The mean analytical recoveries of cTnI were 28.3% (range 7.5-55.1%) and of cTnI-TnC were 23.5% (range 8.7-51.8%) in samples containing IF when antibodies against midfragment epitopes of cTnI were used. The mean recovery of cTnI was 65.1% and 73.3% for antibodies with N- and C-terminal epitopes. Gel filtration of samples with low recovery of cTnI showed that the approximate molecular mass of IF was 50-200 kDa and that the cTnI elution profiles of samples containing IF were shifted towards higher molecular mass compared with samples with less IF., Conclusions: Antibodies against midfragment epitopes of cTnI are affected by IF to a considerable but variable extent, and the presence of IF can be demonstrated by gel filtration.

Background: Cardiac troponins are modified during ischemic injury and are found as a heterogeneous mixture in blood of patients with cardiovascular diseases. We present a strategy to isolate cardiac troponins from human biological material, by use of affinity chromatography, and to provide samples ready for direct analysis by mass spectrometry., Methods: Cardiac troponins were isolated from human left ventricular tissue by affinity chromatography. Isolated troponins were either eluted and analyzed by Western blot or enzymatically digested while bound to affinity beads. The resulting peptide mixture was subjected to mass spectrometry for protein identification and characterization. The same method was used to analyze serum from patients with acute myocardial infarction (AMI)., Results: Affinity chromatography with antibodies specific for one cardiac troponin subunit facilitated the isolation of the entire cardiac troponin complex from myocardial tissue. The three different proteases used for enzymatic digestion increased the total protein amino acid sequence coverage by mass spectrometry for the three cardiac troponin subunits. Combined amino acid sequence coverage for cardiac troponin I, T, and C (cTnI, cTnT, cTnC) was 54%, 48%, and 40%, respectively. To simulate matrix effects on the affinity chromatography-mass spectrometry approach, we diluted tissue homogenate in cardiac troponin-free serum. Sequence coverage in this case was 44%, 41%, and 19%, respectively. Finally, affinity chromatography-mass spectrometry analysis of AMI serum revealed the presence of cardiac troponins in a wide variety of its free and/or complexed subunits, including the binary cTnI-cTnC and cTnI-cTnC-cTnT complexes., Conclusions: Affinity chromatography-mass spectrometry allows the extraction and analysis of cardiac troponins from biological samples in their natural forms. We were, for the first time, able to directly confirm the presence of cardiac troponin complexes in human serum after AMI. This approach could assist in more personalized risk stratification as well as the search for reference materials for cardiac troponin diagnostics.

In patients with acute coronary syndromes cardiac troponins are sensitive markers of myocardial damage. The troponin complex comprises subunits C, T and I and is a major component in the process of myocyte contraction and relaxation. The T and I subunits have cardiac isoforms with distinct specific immunologic properties which distinguish them from similar subunits of non-cardiac muscle tissue. The high sensitivity and specificity of cardiac troponins make them the preferred biochemical markers for diagnosing acute myocardial infarction and for the triage of patients admitted with chest pain without ST segment elevation on the E.K.G. There is a correlation between cardiac troponin levels and prognosis in patients with acute coronary syndromes. In addition to their prognostic role, cardiac troponins play a role in selecting patients for contemporary treatments. Thus, their level can identify the patients most likely to benefit from treatments such as low molecular-weight heparin, IIb/IIIa receptor blockers and early angiography and coronary intervention. Recently, the American heart Association, the European Heart Society and the Israel Cardiology Society have published guidelines for the use of cardiac troponins. This review summarizes the current data regarding the use of cardiac troponins in the acute coronary syndromes.

Background: Current literature suggests that myocarditis is a common event during influenza infection, occurring with a prevalence rate of up to 10%, but these studies have relied on relatively nonspecific techniques of varying sensitivities for the detection of myocyte injury. Using measurement of cardiac troponins I and T, this study sought to determine the prevalence of myocarditis in a large unselected cohort of patients with serologically confirmed acute influenza infection., Methods: A total of 152 subjects were recruited from 60 primary care and university health centers. Serial creatine kinase (CK), CK-MB, and cardiac troponin I and T measurements were taken on days 1, 6, and 21 following presentation., Results: Creatine kinase levels were elevated (mean +/- SD levels, 830 +/- 1531 U/L; range, 181-7280 U/L) during the collection period in 18 patients (12%). Twelve (67%) of these had elevated CK levels on day 1 of presentation. Overall CK-MB levels were higher than 25 U/L in 3 patients with elevated CK readings but in no patient was the CK-MB fraction greater than 6%. Cardiac troponin I and T levels were not raised in any of the patients., Conclusions: Using more sensitive and specific markers of myocardial injury, we demonstrate that the prevalence of myocarditis during acute influenza infection is substantially lower than previously thought, whereas skeletal muscle injury is relatively common. Although we were unable to conclude that no myocardial inflammation was present, it seems likely that this complication is rare.

Implications: The rapid administration of desflurane results in transient hypertension and tachycardia, especially in the presence of sympathetic imbalance. We report a case in which rapid administration of desflurane precipitated an accelerated idioventricular rhythm in a patient. This may have been related to a period of inadequate anesthesia.

Background: Cardiac troponin I (cTnI) is a powerful tool to aid in the diagnosis of myocardial infarction and cardiac muscle damage. We describe an assay that overcomes problems of early assays that were often affected by cTnI degradation, assay interference, poor sensitivity, and imprecision., Methods: The analytical performance of the Access AccuTnI assay (Beckman Coulter) was evaluated at five institutions. Controls, zero calibrator, and diluted patient samples were used to determine precision, detection limit, functional sensitivity, and linearity. The 97.5 and 99 percentiles of a reference population were determined. Common interferents and heterophilic patient samples were tested. Equimolarity was determined by assaying samples with various ratios of free and complexed cTnI. Matched samples drawn into serum, EDTA, lithium heparin, and sodium heparin sample tubes were compared., Results: Total imprecision (CVs) was 4.0-8.8% between 0.40 and 31 microg/L cTnI. The detection limit was <0.01 microg/L. The 97.5 percentile upper reference limit (URL) was 0.03 microg/L (CV = 20%), and the 99 percentile URL was 0.04 microg/L (CV = 14%). Total CVs of 10% and 20% were seen at and above 0.06 and 0.03 microg/L, respectively. The assay was linear to >60 microg/L and not affected by common assay interferents. An equimolar response was observed with free, complexed, phosphorylated, and dephosphorylated forms of cTnI. Results were 4% lower in serum and 14% lower in EDTA plasma than in lithium heparin plasma (P <0.01), independent of cTnI concentration., Conclusion: AccuTnI is a sensitive and precise assay for the measurement of cTnI.

Currently available serum markers of cardiac injury in patients with renal insufficiency suffer from impaired sensitivity and specificity. Cardiac troponins (cTnI, cTnT) are relatively new diagnostic markers of myocardial injury and have gained widespread application in the non-renal-failure population to diagnose myocardial infarction. Over the past few years the specificity and sensitivity of cardiac troponins for diagnosing acute myocardial infarction in patients with renal dysfunction have been examined. Most data indicate that cardiac troponin I has an excellent specificity, but until more studies are available this marker should be considered a useful but imperfect serum marker of an acute coronary syndrome in patients with underlying renal dysfunction.

Purpose of the Study: Heart contusion is a severe injury for the diagnosis of which there still doesn't exist a uniform procedure. The aim of the work was to compare individual methods and provide opinion on the justification of their use., Material: In the period of 1998-2000 at the authors' departments 103 patient were hospitalised with a severe contusion of the chest. These patients were admitted at the department within 24 hours after the injury., Methods: The diagnosis was based on the examination of the ratio of CKMB/CK serum levels, cTnl serum level, ECG examination and echocardiography., Results: Heart contusion was diagnosed in 18 patients of the group of 103. The most precise diagnostic method proved to be the determination of the serum level of troponin I (success rate 86%) and echocardiographic examination (succes rate 67%)., Conclusions: Examination of cTnl serum level and echocardiography are the best methods for the determination of the diagnosis of heart contusion. Simultaneous application of these two methods is the most reliable diagnostic procedure. Examination of CK and CKMB serum levels produces often falsely positive results and it is not a contribution to the determination of the diagnosis of heat contusion.

Due to myocyte damage and an associated inflammatory response, it is possible that cardiac troponin T and C-reactive protein (CRP) concentrations may correlate with the histologic grade of rejection in endomyocardial biopsy samples obtained from patients who have received a heart transplant. In this study, 704 blood samples were obtained from 145 different heart transplant recipients just prior to endomyocardial biopsy. Plasma specimens were assayed for troponin T and CRP concentration and the results compared with the assigned International Society of Heart and Lung Transplantation (ISHLT) histologic grade. Rejection was defined as an ISHLT grade of 3A or higher. The negative predictive values were near 80% in all cases, and a statistically significant increase in median troponin T concentration was observed across ISHLT grades. After the first month posttransplantation, the specificity of the troponin T test (cutoff 0.1 ng/ml) was 95% and increased to 98% when false positives seen in renal disease patients were excluded. Both tests demonstrated poor sensitivity and positive predictive value for rejection. Neither CRP nor troponin T had sufficient sensitivity to serve as an alternative to endomyocardial biopsy in the diagnosis of acute cardiac allograft rejection. However, the troponin T test had a high specificity, especially when patients with renal insufficiency were excluded, and could serve as an adjunct test in this setting. When combined with a normal serum creatinine, a troponin T > or =0.1 ng/ml prior to endomyocardial biopsy correlated with graft rejection in almost all cases, making biopsy unnecessary.

Biochemical markers of myocardial damage are together with the clinical history, the physical examination and the 12-lead ECG key elements in the clinical evaluation of patients presenting with symptoms suggestive of an acute coronary syndrome (ACS). In this situation the detection of myocardial damage, even very minor, is of importance, not only for diagnosis, but also for risk assessment and selection of treatment. The new markers of myocardial damage. troponin T and I, have been shown to offer some advantages over the conventional markers in ACS and there is also an increasing interest for troponins in other clinical situations, e.g. after surgery and percutaneous coronary intervention. This paper will discuss the role of troponins in these different clinical situations.

Fourteen monoclonal antibodies (mAbs) against human cardiac troponin I (cTnI) were generated by commonly used experimental techniques. All these antibodies, as well as antibody 414 (HyTest), were specific for human cTnI. Fifteen antibodies thus obtained were tested in a sandwich cTnI immunofluorescence assay (altogether 196 combinations). Ten pairs giving the highest sensitivity were selected for further investigation. The effect of TnI-TnC complex formation on antibody interaction with antigen was analyzed. The formation of TnI-TnC complex results in a significant decrease of the interaction of mAbs with TnI for seven of 10 analyzed pairs of antibodies. Using two pairs of cTnI-specific mAbs, one that recognized only free cTnI but not cTnI complexed with cTnC, and another that could be used for measurement of total cTnI (free cTnI and cTnI in complex with cTnC), we demonstrated that the main part of cTnI in serum collected from acute myocardial infarction patients is presented in the complex from. We concluded that effective and reliable immunological detection of TnI is possible only when antibodies used for assay development recognize both free TnI and TnI complexed with other troponin components.