scholarly journals Cardiac Troponins are Among Targets of Doxorubicin-Induced Cardiotoxicity in hiPCS-CMs

2019 ◽  
Vol 20 (11) ◽  
pp. 2638 ◽  
Author(s):  
Michaela Adamcova ◽  
Veronika Skarkova ◽  
Jitka Seifertova ◽  
Emil Rudolf
Keyword(s):  
Cardiac Troponin ◽  
Troponin I ◽  
Troponin T ◽  
Early Recognition ◽  
Morphological Changes ◽  
Cancer Therapeutics ◽  
Diagnostic Strategies ◽  
Human Cardiomyocytes ◽  
Induced Pluripotent ◽  
Cardiac Troponins

Modern diagnostic strategies for early recognition of cancer therapeutics-related cardiac dysfunction involve cardiac troponins measurement. Still, the role of other markers of cardiotoxicity is still unclear. The present study was designed to investigate dynamics of response of human cardiomyocytes derived from induced pluripotent stem cells (hiPCS-CMs) to doxorubicin with the special emphasis on their morphological changes in relation to expression and organization of troponins. The hiPCS-CMs were treated with doxorubicin concentrations (1 and 0.3 µM) for 48 h and followed for next up to 6 days. Exposure of hiPCS-CMs to 1 µM doxorubicininduced suppression of both cardiac troponin T (cTnT) and cardiac troponin I (cTnI) gene expression. Conversely, lower 0.3 µM doxorubicin concentration produced no significant changes in the expression of aforementioned genes. However, the intracellular topography, arrangement, and abundance of cardiac troponin proteins markedly changed after both doxorubicin concentrations. In particular, at 48 h of treatment, both cTnT and cTnI bundles started to reorganize, with some of them forming compacted shapes extending outwards and protruding outside the cells. At later intervals (72 h and onwards), the whole troponin network collapsed and became highly disorganized following, to some degree, overall changes in the cellular shape. Moreover, membrane permeability of cardiomyocytes was increased, and intracellular mitochondrial network rearranged and hypofunctional. Together, our results demonstrate complex effects of clinically relevant doxorubicin concentrations on hiPCS-CM cells including changes in cTnT and cTnI, but also in other cellular compartments contributing to the overall cytotoxicity of this class of cytostatics.

Cardiac troponins and mortality in type 1 and 2 myocardial infarction

2017 ◽  
Vol 55 (2) ◽  
Author(s):  
Giuseppe Lippi ◽  
Fabian Sanchis-Gomar ◽  
Gianfranco Cervellin
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Troponin T ◽  
Post Discharge ◽  
Assay Sensitivity ◽  
Percentage Difference ◽  
Cardiac Troponins

AbstractBackground:The pathogenesis of different types of myocardial infarction (MI) differs widely, so that accurate and timely differential diagnosis is essential for tailoring treatments according to the underlying causal mechanisms. As the measurement of cardiac troponins is a mainstay for diagnosis and management of MI, we performed a systematic literature analysis of published works which concomitantly measured cardiac troponins in type 1 and 2 MI.Methods:The electronic search was conducted in Medline, Scopus and Web of Science using the keywords “myocardial infarction” AND “type(-)2” OR “type II” AND “troponin” in “Title/Abstract/Keywords”, with no language restriction and date limited from 2007 to the present.Results:Overall, 103 documents were identified, but 95 were excluded as precise comparison of troponin values in patients with type 1 and 2 MI was unavailable. Therefore, eight studies were finally selected for our analysis. Two studies used high-sensitivity (HS) immunoassays for measuring cardiac troponin T (HS-TnT), one used a HS immunoassay for measuring cardiac troponin I (HS-TnI), whereas the remaining used conventional methods for measuring TnI. In all studies, regardless of type and assay sensitivity, troponin values were higher in type 1 than in type 2 MI. The weighted percentage difference between type 1 and 2 MI was 32% for TnT and 91% for TnI, respectively. Post-discharge mortality obtained from pooling individual data was instead three times higher in type 2 than in type 1 MI.Conclusions:The results of our analysis suggest that the value of cardiac troponins is consistently higher in type 1 than in type 2 MI.

Elevated Cardiac Troponin in the Setting of Periodic Symptomatology: A Case Report

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S89-S90
Author(s):  
J M Rohr ◽  
S Pirruccello ◽  
A Sofronescu
Keyword(s):  
Chest Pain ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Troponin T ◽  
Clinical Chemistry ◽  
Package Insert ◽  
Clinical Diagnostics ◽  
Heterophile Antibody ◽  
Tertiary Center ◽  
Cardiac Troponins

Abstract Introduction/Objective Serial cardiac troponin measurement is a sensitive method to identify recent cardiac injury and is a necessary function of the clinical chemistry laboratory. We present a case of out-of-range cardiac troponin I (cTnI) elevation which remained spuriously elevated for at least 30 days. Methods Cardiac troponins were measured on a DxI (Beckman Coulter), Vitros 5600 (Ortho Clinical Diagnostics), iSTAT (Abbott), and Cobas e602 (Roche) according to the manufacturers’ instructions with appropriate controls. Heterophile antibody blocking (Scantibodies Laboratories) was performed according to the package insert. Results A 58-year-old male with a medical history significant for chronic non-ischemic cardiomyopathy with open valvular repair (ejection fraction 15-20%), chronic atrial fibrillation, and Hodgkin’s lymphoma in remission presented to a rural clinic with chest pain and a cTnI of 0.8 ng/mL (reference <0.04 ng/mL). He was transferred to our tertiary center for open revision. The patient’s cTnI (measured on a Beckman Coulter DxI) was above linearity threshold (>71.00 ng/mL) starting day 1 after surgery. The patient self-discharged against medical advice on day 16. On day 21 he experienced new chest pain and dyspnea and was readmitted with a cardiac troponin T (cTnT) of >35 ng/mL (iSTAT; reference <0.08 ng/mL) and cTnI again above threshold. This value remained elevated for the next five days despite abated symptoms. To address the discordant laboratory and physical findings, dilutional cTnI measurements on serum from day 30 demonstrated linearity. Heterophile antibody testing was negative. cTnI on the DxI machine remained >71.00 ng/mL but was separately measured as 3.4 ng/mL (Vitros 5600, reference <0.08 ng/mL). cTnT was found to be 1.05 ng/mL (Cobas e602; reference 0.00 ng/mL). Comparative examination of all methodologies was unrevealing. Conclusion This case demonstrates a spurious elevation of cardiac troponins which remarkably demonstrated linearity on serial dilution. Multiple testing methodologies were necessary to prove fallacy. The cause of the result remains unclear. The clinical pathologist should be aware of possible false positives and investigate unlikely continuous cardiac troponin elevations.

scholarly journals Inconsistent Findings of Cardiac Troponin T and I in Clinical Routine Diagnostics: Factors of Influence

2021 ◽  
Vol 10 (14) ◽  
pp. 3148
Author(s):  
Abass Eidizadeh ◽  
Laura Fraune ◽  
Andreas Leha ◽  
Rolf Wachter ◽  
Abdul R. Asif ◽  
...  
Keyword(s):  
Sensitivity And Specificity ◽  
Cardiac Troponin ◽  
Roc Analysis ◽  
Troponin I ◽  
Troponin T ◽  
Clinical Routine ◽  
Routine Diagnostics ◽  
Negative Results ◽  
Factors Of Influence ◽  
Cardiac Troponins

Cardiac troponins are crucial for the diagnosis of acute myocardial infarction. Despite known differences in their diagnostic implication, there are no recommendations for only one of the two troponins, cardiac troponin I (cTnI) and troponin T (cTnT) so far. In an everyday routine diagnostic, cTnT (Roche) as well as cTnI (Abbott) were measured in 5667 samples from 3264 patient cases. We investigated the number of identical or discrepant troponin findings. Regarding cTnI, we considered both, sex-dependent and unisex cutoffs. In particular, the number of cTnT positive and cTnI negative results was strikingly high in 14.0% of cTnT positive samples and increases to 23.8% by using sex-specific cTnI cutoffs. This group was considerably greater than the group of cTnI positive and cTnT negative results, also after elimination of patients with an eGFR < 60 mL/min/1.73 m2. Comparing the troponin cases with a dynamic increase or decrease between two measurements, we saw a balanced number of discrepant cases (between cTnT+/cTnI− and cTnT−/cTnI+), which was, however, still present. Using ROC analysis, sex-dependent cutoffs improved sensitivity and specificity of cTnI. This study shows in a large cohort that comparing the two cardiac troponins does not amount to identical analytical results. Consideration of sex-dependent cutoffs may improve sensitivity and specificity.

scholarly journals Cardiac Troponins in Patients with Renal Dysfunction

1998 ◽  
Vol 35 (3) ◽  
pp. 380-386 ◽  
Author(s):  
P O Collinson ◽  
L Hadcocks ◽  
Y Foo ◽  
S B Rosalki ◽  
P J Stubbs ◽  
...  
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Detection Limit ◽  
Renal Dysfunction ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Troponin T ◽  
Multiple Organ ◽  
Chronic Renal Impairment ◽  
Cardiac Troponins

Cardiac troponin T (cTnT) and cardiac troponin I (cTnI) were measured in 198 patients with renal dysfunction [132 men: median (range) age 66·1 (8·2-90·3) years]. cTnT was measured by two methods: ELISA and Enzymun (Boehringer Mannheim UK, Lewes, UK), both with a detection limit of 0·05 μg/L in 179 and 78 patients, respectively. cTnI was measured in 80 patients by the OPUS plus and OPUS Magnum systems (Dade-Behring, Milton Keynes, UK) with a detection limit of 0·5 μg/L. Patients were classified as having chronic renal impairment (CRI), chronic renal failure (CRF), acute renal failure including those with multiple organ failure on renal replacement therapy (ARF), and patients with chronic renal failure treated with haemodialysis (HD). Cardiac troponins were detectable in the serum of patients with renal dysfunction. cTnT was detectable in 113/179 (63·1%) and 33/78 (42·3%) by the ELISA and Enzymun methods respectively. cTnI was detectable in 17/80 (21·3%). cTnT (ELISA and Enzymun methods) and cTnI were detectable with increased frequency in the CRF, HD and ARF patient groups compared with the CRI group. Cardiac troponin concentrations did not correlate with serum creatine kinase (CK) activity, CK-MB, or urea or creatinine levels. Serial cardiac troponin measurements may be required to confirm or exclude a diagnosis of acute coronary syndromes in patients with renal dysfunction.

scholarly journals Cardiac Troponins and Renal Function in Nondialysis Patients with Chronic Kidney Disease

2005 ◽  
Vol 51 (11) ◽  
pp. 2059-2066 ◽  
Author(s):  
Nasir A Abbas ◽  
R Ian John ◽  
Michelle C Webb ◽  
Michelle E Kempson ◽  
Aisling N Potter ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Troponin T ◽  
Left Ventricular ◽  
Reference Limit ◽  
Coronary Syndrome ◽  
Stage 4 ◽  
Cardiac Troponins

Abstract Background: Serum cardiac troponin concentrations are commonly increased in end-stage renal disease (ESRD) in the absence of an acute coronary syndrome (ACS). The data on cardiac troponin I (cTnI) are more variable than those for cardiac troponin T (cTnT). There is little information on cardiac troponin concentrations in patients with chronic kidney disease (CKD) who have not commenced dialysis. Methods: We studied 222 patients: 56 had stage 3 (moderate CKD); 70 stage 4 (severe CKD); and 96 stage 5 (kidney failure). Patients underwent echocardiography and were followed prospectively for a median of 19 months; all-cause mortality was recorded. Results: Overall, serum cTnT was increased above the 99th percentile reference limit in 43% of all CKD patients studied, compared with 18% for cTnI. Serum cTnT and cTnI concentrations were more commonly increased in the presence of more severe CKD (11 and 6 patients in stage 3, 27 and 8 in stage 4, and 57 and 24 in stage 5 (P &lt;0.0001 and &lt;0.02, respectively). Among 38 patients with detectable cTnI, 32 had detectable cTnT (rs = 0.67; P&lt;0.0001). There was evidence that decreasing estimated glomerular filtration rate increased the odds of having detectable cTnT (P &lt;0.001) but not cTnI (P = 0.128). There was no evidence to support an adjusted association of detectable cardiac troponins with increasing left ventricular mass index. Increased cTnT (P = 0.0097), but not cTnI, was associated with decreased survival. Conclusions: Increased cTnT and cTnI concentrations are relatively common in predialysis CKD patients, in the absence of an ACS, including among those with stage 3 disease. The presence of left ventricular hypertrophy alone does not explain these data. Detectable cTnT was a marker of decreased survival.

scholarly journals Neuregulin-1 attenuated doxorubicin-induced decrease in cardiac troponins

2009 ◽  
Vol 297 (6) ◽  
pp. H1974-H1983 ◽  
Author(s):  
Yun Bian ◽  
Maoyun Sun ◽  
Marcy Silver ◽  
Kalon K. L. Ho ◽  
Mark A. Marchionni ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Troponin T ◽  
Neonatal Rat ◽  
Caspase Activation ◽  
Neuregulin 1 ◽  
Proteasome Degradation ◽  
Phosphorylated Akt ◽  
Cardiac Troponins

Neuregulin-1 (NRG1) is a potential therapeutic agent for the treatment of doxorubicin (Dox)-induced heart failure. NRG1, however, activates the erbB2 receptor, which is frequently overexpressed in breast cancers. It is, therefore, important to understand how NRG1, via erbB2, protects the heart against Dox cardiotoxicity. Here, we studied NRG1-erbB2 signaling in Dox-treated mice hearts and in isolated neonatal rat ventricular myocytes (NRVM). Male C57BL/6 mice were treated with recombinant NRG1 before and daily after a single dose of Dox. Cardiac function was determined by catheterization. Two-week survival was analyzed by the Kaplan-Meier method. Cardiac troponins [cardiac troponin I (cTnI) and cardiac troponin T (cTnT)] and phosphorylated Akt protein levels were determined in mice hearts and in NRVM by Western blot analysis. Activation of caspases and ubiquitinylation of troponins were determined in NRVM by caspase assay and immunoprecipitation. NRG1 significantly improved survival and cardiac function in Dox-treated mice. NRG1 reduced the decrease in cTnI, cTnT, and cardiac troponin C (cTnC) and maintained Akt phosphorylation in Dox-treated mice hearts. NRG1 reduced the decrease in cTnI and cTnT mRNA and proteins in Dox-treated NRVM. Inhibition of erbB2, phosphoinositide 3-kinase (PI3K), Akt, and mTOR blocked the protective effects of NRG1 on cTnI and cTnT in NRVM. NRG1 significantly reduced Dox-induced caspase activation, which degraded troponins, in NRVM. NRG1 reduced Dox-induced proteasome degradation of cTnI. NRG1 attenuates Dox-induced decrease in cardiac troponins by increasing transcription and translation and by inhibiting caspase activation and proteasome degradation of troponin proteins. NRG1 maintains cardiac troponins by the erbB2-PI3K pathway, which may lessen Dox-induced cardiac dysfunction.

scholarly journals Measurement of Cardiac Troponins

2001 ◽  
Vol 38 (5) ◽  
pp. 423-449 ◽  
Author(s):  
Paul O Collinson ◽  
Frances G Boa ◽  
David C Gaze
Keyword(s):  
Gold Standard ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Regulatory Mechanism ◽  
Troponin T ◽  
Myocardial Damage ◽  
Myocardial Cell ◽  
Cell Necrosis ◽  
Form Part ◽  
Cardiac Troponins

The cardiac troponins form part of the regulatory mechanism for muscle contraction. Specific cardiac isoforms of cardiac troponin T and cardiac troponin I exist and commercially available immunoassay systems have been developed for their measurement. A large number of clinical and analytical studies have been performed and the measurement of cardiac troponins is now considered the ‘gold standard’ biochemical test for diagnosis of myocardial damage. There have been advances in understanding the development and structure of troponins and their degradation following myocardial cell necrosis. This has contributed to the understanding of the problems with current assays. Greater clinical use has also highlighted areas of analytical and clinical confusion. The assays are reviewed based on manufacturers' information, current published material as well as the authors' in-house experience.

scholarly journals Clinical relevance of biological variation of cardiac troponins

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Aldo Clerico ◽  
Andrea Padoan ◽  
Martina Zaninotto ◽  
Claudio Passino ◽  
Mario Plebani
Keyword(s):  
Cardiovascular Risk ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Troponin T ◽  
High Sensitivity ◽  
Systemic Hypertension ◽  
Diagnostic Process ◽  
Chronic Obstructive ◽  
Screening Programs ◽  
Cardiac Troponins

AbstractThe high-sensitivity immunoassays for cardiac troponin I (hs-cTnI) and cardiac troponin T (hs-cTnT) are recommended by all the most recent international guidelines as gold standard laboratory methods for the detection of myocardial injury and diagnosis of acute myocardial infarction (AMI). In this review article, the Authors aimed at discussing the relevant biochemical, physiological, and clinical issues related to biological variability of cTnI and cTnT. Cardiac troponins, measured with hs-cTn methods, show a better clinical profile than the other cardio-specific biomarkers (such as the natriuretic peptides, BNP and NT-proBNP). In particular, the hs-cTn methods are characterized by a low intra-individual index of variation (<0.6) and reduced analytical imprecision (about 5% CV) at the clinical cut-off value (i.e., the 99th percentile URL value). Moreover, recent studies have reported that differences between two hs-cTn measured values (RCV) >30% can be considered statistically significant. These favourable biological characteristics and analytical performance of hs-cTn methods significantly improved the accuracy in the diagnostic process of acute coronary syndromes (ACS) in patients admitted to emergence department. In addition, several studies have demonstrated the clinical usefulness of cardiovascular risk evaluation with hs-cTn methods in some groups of patients with clinical conditions at high cardiovascular risk (such as systemic hypertension, severe obesity, diabetes mellitus, renal insufficiency, and chronic obstructive pulmonary disease). However, screening programs in the general population with hs-cTn methods for cardiovascular risk stratification require further investigation to define the optimal target populations, timing of measurement, and preventive interventions.

1461-P: Cardiac Troponin T and Troponin I and Incident Diabetes in the General Population: Generation Scotland Scottish Family Health Study

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1461-P
Author(s):  
PAUL WELSH ◽  
DAVID PREISS ◽  
ARCHIE CAMPBELL ◽  
DAVID J. PORTEOUS ◽  
NICHOLAS L. MILLS ◽  
...  
Keyword(s):  
General Population ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Troponin T ◽  
Family Health ◽  
Incident Diabetes ◽  
Health Study ◽  
Cardiac Troponin T ◽  
Generation Scotland

Postmortem Specificity of Troponin for Acute Miocard Infarction Diagnosis throug Qualitative Dosing from Pericardial Fluid

2018 ◽  
Vol 69 (9) ◽  
pp. 2482-2486
Author(s):  
Iuliana Hunea ◽  
Simona Irina Damian ◽  
Carmen Corina Radu ◽  
Sorin Moldoveanu ◽  
Tatiana Iov
Keyword(s):  
Sudden Cardiac Death ◽  
Cardiac Disease ◽  
Cardiac Death ◽  
Troponin I ◽  
Troponin T ◽  
Morphological Changes ◽  
Pericardial Fluid ◽  
Histological Changes ◽  
Lethal Arrhythmia ◽  
Myocardial Lesions

Cardiac disease is the leading cause of death, and sudden cardiac death occupies the first place in sudden deaths of natural causes. Sudden cardiac death due to lethal arrhythmia may be the first manifestation of a cardiac disease, such cases becoming suspect dead, thus forensic cases. The autopsy performed in such cases may reveal important cardiovascular disease but not obvious macroscopic or histological changes of acute myocardial infarction (IMA), except for cases of survival for several hours after the onset of the symptomatology. Biochemical markers were used to test for myocardial lesions in the absence of morphological changes. Methods for determining myoglobin, CK-MB, troponin T (cTn T), troponin I (cTn I) were introduced to the clinic to diagnose the condition of patients with chest pain as early as the 1990s. The lack of pathognomonic elements in corps investigations, where part of the analysis cannot be carried out, requires verification of the value of the investigations that can be carried out, with reference to the biochemical in the present case, in establishing the diagnosis with certainty.

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