P2612Elevated cardiac troponin T but not troponin I in patients with skeletal muscle disease

Abstract Background: The expression of multiple cardiac troponin T (cTnT) isoforms has been demonstrated in diseased human skeletal muscle. However, cardiac troponin I (cTnI) expression has been described only in heart muscle. The goal of this study was to determine whether mRNA for cTnT, slow skeletal troponin T (sTnT), or cTnI was expressed in skeletal muscle biopsies obtained from patients with end-stage renal disease (ESRD) and Duchenne muscular dystrophy (DMD). Methods: Total mRNA was extracted from healthy human heart (n = 4), healthy human skeletal muscle (n = 5), and skeletal muscle from patients with ESRD (n = 7) and DMD (n = 5). Total RNA (1 μg) was reverse-transcribed using Moloney murine leukemia virus reverse transcriptase. The reverse-transcribed cDNAs were amplified by PCR using oligonucleotide primers specific for cTnT, sTnT, and cTnI sequences (GenBank accession numbers X74819, m19308, and X54163, respectively). Results: In all heart specimens, a 150-bp cTnT amplicon was detected. Skeletal muscle from four of seven patients with ESRD and two of five patients with DMD showed expression of a 150-bp amplicon. Using DNA sequencing and a comparison program, the 150-bp amplicons found in heart and diseased skeletal muscle specimens were 100% identical and specific to the cTnT mRNA sequence. No cTnT mRNA expression was found in healthy skeletal muscle. No evidence of sTnT mRNA was found in heart muscle. A 200-bp sTnT amplicon specific to a human sTnT sequence was detected in all skeletal muscle specimens. A 250-bp cTnI amplicon specific to the cTnI sequence was detected in all heart specimens. However, no cTnI mRNA expression was found in healthy or diseased skeletal muscle specimens. cTnT mRNA expression in both heart and diseased skeletal muscles corresponded with cTnT isoform expression, respectively, as determined by Western blot analysis. Conclusion: Our findings demonstrate cTnT mRNA expression, but no cTnI mRNA expression, by reverse transcription-PCR in diseased human skeletal muscle that expresses cTnT isoforms.

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

Diabetes ◽

10.2337/db19-1461-p ◽

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

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Cardiac troponin I, cardiac troponin T, and creatine kinase MB in dialysis patients without ischemic heart disease: evidence of cardiac troponin T expression in skeletal muscle

Clinical Chemistry ◽

10.1093/clinchem/43.6.976 ◽

1997 ◽

Vol 43 (6) ◽

pp. 976-982 ◽

Cited By ~ 133

Author(s):

Mary D McLaurin ◽

Fred S Apple ◽

Ellen M Voss ◽

Charles A Herzog ◽

Scott W Sharkey

Keyword(s):

Skeletal Muscle ◽

Heart Disease ◽

Ischemic Heart Disease ◽

Cardiac Troponin ◽

First Generation ◽

Troponin T ◽

Ischemic Heart ◽

Cardiac Troponin T ◽

Dialysis Patients ◽

Acute Ischemic Heart Disease

Abstract Serum cardiac troponin T (cTnT) concentrations are frequently increased in chronic dialysis patients as measured by the first-generation ELISA immunoassay, as is creatine kinase (CK) MB mass in the absence of acute ischemic heart disease. We designed this study to compare four serum markers of myocardial injury [CK-MB mass, first-generation ELISA cTnT, second-generation Enzymun cTnT, and cardiac troponin I (cTnI)] in dialysis patients without acute ischemic heart disease. We also evaluated skeletal muscle from dialysis patients as a potential source of serum cTnT. No patients in the clinical evaluation group (n = 24) studied by history and by physical examination, electrocardiography, and two-dimensional echocardiography had evidence of ischemic heart disease. Biochemical markers were measured in serial predialysis blood samples with specific monoclonal antibody-based immunoassays. For several patients at least one sample measured above the upper reference limit: CK-MB, 7 of 24 (30%); ELISA cTnT, 17 of 24 (71%); Enzymun cTnT, 3 of 18 (17%); and cTnI, 1 of 24 (4%). In a separate group of dialysis patients (n = 5), expression of cTnT, but not cTnI, was demonstrated by Western blot analysis in 4 of 5 skeletal muscle biopsies. Chronic dialysis patients without acute ischemic heart disease frequently had increased serum CK-MB and cTnT. The specificity of the second-generation cTnT (Enzymun) assay was improved over that of the first-generation (ELISA) assay; cTnI was the most specific of the currently available biochemical markers. cTnT, but not cTnI, was expressed in the skeletal muscle of dialysis patients.

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P4420Is exercise-induced cardiac troponin release caused by skeletal muscle injury?

European Heart Journal ◽

10.1093/eurheartj/ehz745.0822 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

T Paana ◽

S Jaakkola ◽

E Tuunainen ◽

S Wittfooth ◽

K Bamberg ◽

...

Keyword(s):

Skeletal Muscle ◽

Cardiac Troponin ◽

Muscle Injury ◽

Troponin I ◽

Troponin T ◽

Skeletal Muscle Injury ◽

Coronary Syndrome ◽

Marathon Race ◽

Recreational Runners ◽

Exercise Induced

Abstract Background Cardiac troponins (cTn) are highly sensitive and specific markers for cardiac injury and a key element in the diagnosis of acute coronary syndrome. Strenuous exercise is known to induce increases in cTn, but the causative factors remain ambiguous. It is also equivocal whether exercise induced skeletal muscle injury is associated with cTn elevation. Purpose The aim of this study was to identify independent predictors for the rise in cardiac troponin T (cTnT) and I (cTnI) concentration and to focus on the relationship between skeletal muscle injury measured by skeletal troponin I (skTnI) and cTn elevations after a marathon race in a large group of male recreational runners. Methods A total of 40 recreational runners participating in the marathon in our city were recruited. The study included baseline visit (prerace) and immediate post-race sampling. Results The post-marathon cTnT concentration rose above the reference limit in 38 (95%) participants and the detection limit for cTnI was exceeded in 34 (85%) participants. Similarly, a 10-fold increase in skTnI concentration was observed and elevated post-race values were seen in all participants. There was no significant correlation between the post-race cTnT or cTnT change and post-race skTnI (Spearman's rho = 0.249, p=0.122, rho = 0.285, p=0.074). However, post-race cTnI and change in cTnI were associated with post-race skTnI (rho = 0.404, p=0.01, rho = 0.460, p=0.003) and creatine kinase (r=0.368, p=0.019) concentration. Subjective exertion or self-reported muscle symptoms did not correlate with post-race cTnT, cTnI or skTnI levels. Post-Race cTnT <40 Post-Race cTnT ≥40 p-value n=18 n=22 Age, years 53.3±12.2 44.0±11.9 0.002 Active training, years 12.0 (9.3) 17.0 (15.8) 0.190 Muscle symptoms 7 (38.9) 11 (52.4) 0.523 Creatinine kinase, ug/l 406 (137) 399 (319) 0.163 N-terminal proBNP ng/l 137±168 158±277 0.783 Skeletal Troponin I, ng/ml 28.6 (41) 56.7 (143) 0.199 Figure 1 Conclusions Cardiac troponin became abnormal in almost all runners after marathon race. The exercise-induced rise in cardiac troponin I is related to simultaneous release of skeletal troponin I. The mechanism of this association remains uncertain, but clinicians should be cautious when interpreting post-exercise troponin levels without clinical symptoms and signs of myocardial ischemia.

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Cardiac Troponin Complex: Cardiac Troponin C (TNNC1), Cardiac Troponin I (TNNI3), and Cardiac Troponin T (TNNT2)

Encyclopedia of Signaling Molecules ◽

10.1007/978-1-4614-6438-9_101901-1 ◽

2016 ◽

pp. 1-10

Author(s):

Zabed Mahmud ◽

Peter M. Hwang

Keyword(s):

Cardiac Troponin ◽

Troponin I ◽

Troponin T ◽

Troponin C ◽

Cardiac Troponin I ◽

Cardiac Troponin T ◽

Cardiac Troponin C ◽

Troponin Complex

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Multicenter evaluation of a second-generation assay for cardiac troponin T

Clinical Chemistry ◽

10.1093/clinchem/43.10.1877 ◽

1997 ◽

Vol 43 (10) ◽

pp. 1877-1884 ◽

Cited By ~ 62

Author(s):

Hannsjörg Baum ◽

Siegmund Braun ◽

Willie Gerhardt ◽

Georges Gilson ◽

Gerd Hafner ◽

...

Keyword(s):

Skeletal Muscle ◽

Cardiac Troponin ◽

First Generation ◽

Second Generation ◽

Troponin T ◽

Myocardial Damage ◽

Cross Reactivity ◽

Cardiac Troponin T ◽

Marathon Runners ◽

Assay Time

Abstract We report on the evaluation of the second-generation assay for cardiac troponin T (cTnT) on the Enzymun®system. This new assay is completely specific for the cardiac isoform of TnT, utilizing two cardiospecific monoclonal antibodies. The assay time is reduced to 45 min. The interassay precision shows a median CV of 5.5%; 20% interassay CV was found between 0.05 and 0.1 μg/L. The cardiosensitivity of the second-generation cTnT assay in patients with ischemic myocardial injury appears equivalent when compared with the first-generation assay. We found no falsely positive results in patients with skeletal muscle damage including multitraumas, surgery patients, and marathon runners who showed highly increased values with the unspecific first-generation assay. In Duchenne disease cTnT was still increased, but to a much lower extent. cTnT remains increased in renal failure, but to a lesser degree than with the first-generation assay. The cause of this increase remains unclear. Although a cross-reactivity of skeletal muscle TnT in the second-generation assay could be excluded by our findings, minor myocardial damage or expression of the cardiac isoform of TnT in regenerating muscles cannot be ruled out in those cases with apparently falsely increased cTnT values. The second-generation cTnT assay is a step forward in the combination of cardiosensitivity and cardiospecificity in biochemical markers for diagnosis of heart disease.

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Biological variation of cardiac troponins in chronic kidney disease

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/0004563220906431 ◽

2020 ◽

Vol 57 (2) ◽

pp. 162-169

Author(s):

RA Jones ◽

J Barratt ◽

EA Brettell ◽

P Cockwell ◽

RN Dalton ◽

...

Keyword(s):

Myocardial Infarction ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Cardiac Troponin ◽

Troponin I ◽

Troponin T ◽

Biological Variation ◽

Cardiac Troponin I ◽

Cardiac Troponin T ◽

Reference Change Value

Background Patients with chronic kidney disease often have increased plasma cardiac troponin concentration in the absence of myocardial infarction. Incidence of myocardial infarction is high in this population, and diagnosis, particularly of non ST-segment elevation myocardial infarction (NSTEMI), is challenging. Knowledge of biological variation aids understanding of serial cardiac troponin measurements and could improve interpretation in clinical practice. The National Academy of Clinical Biochemistry (NACB) recommended the use of a 20% reference change value in patients with kidney failure. The aim of this study was to calculate the biological variation of cardiac troponin I and cardiac troponin T in patients with moderate chronic kidney disease (glomerular filtration rate [GFR] 30–59 mL/min/1.73 m2). Methods and results Plasma samples were obtained from 20 patients (median GFR 43.0 mL/min/1.73 m2) once a week for four consecutive weeks. Cardiac troponin I (Abbott ARCHITECT® i2000SR, median 4.3 ng/L, upper 99th percentile of reference population 26.2 ng/L) and cardiac troponin T (Roche Cobas® e601, median 11.8 ng/L, upper 99th percentile of reference population 14 ng/L) were measured in duplicate using high-sensitivity assays. After outlier removal and log transformation, 18 patients’ data were subject to ANOVA, and within-subject (CVI), between-subject (CVG) and analytical (CVA) variation calculated. Variation for cardiac troponin I was 15.0%, 105.6%, 8.3%, respectively, and for cardiac troponin T 7.4%, 78.4%, 3.1%, respectively. Reference change values for increasing and decreasing troponin concentrations were +60%/–38% for cardiac troponin I and +25%/–20% for cardiac troponin T. Conclusions The observed reference change value for cardiac troponin T is broadly compatible with the NACB recommendation, but for cardiac troponin I, larger changes are required to define significant change. The incorporation of separate RCVs for cardiac troponin I and cardiac troponin T, and separate RCVs for rising and falling concentrations of cardiac troponin, should be considered when developing guidance for interpretation of sequential cardiac troponin measurements.

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