Variation of pre- and post-race cardiac troponin concentrations in Thoroughbred and Arabian racehorses

From Creatine Kinase-MB to Troponin

The aim of this study was to assess the role of serum cardiac troponin I (cTnI), troponin T (cTnT), lactate dehydrogenase (LDH) and MB isoenzyme of CK (CK-MB) concentrations in the detection of cardiac injury in dogs with chronic mitral valve disease (CMVD). Fiftyfive dogs with echocardiographic diagnosis of CMVD defined as cardiac thrill (Ct) and non-cardiac thrill (nCt) by auscultation-palpation, and ten control dogs were studied. Serum was extracted from a blood sample from each dog. Analysis of serum cTnI, cTnT, LDH and CK-MB concentrations were performed. Mean ± SD serum cTnI concentration was 1.9 ± 0.38 ng/mL in group-Ct and 1.75 ± 0.27 ng/mL in group-nCt, and cTnI concentrations in both the subgroups were significantly higher than in the control dogs (P<0.01). cTnT and CK-MB concentrations were 0.031 ± 0.02 ng/mL and 83.5 ± 88.4 IU/L in group-Ct and 0.024 ± 0.01 ng/mL and 51.6 ± 47.4 IU/L in group-nCt, respectively. Mean cTnT and CK-MB concentrations in group-Ct were significantly higher than in control dogs (P<0.01, P<0.05). LDH concentration was 918 ± 136.4 IU/L in group-Ct and 351 ± 140.7 IU/L in group-nCt. A significant difference in serum LDH concentrations was observed between the 3 studied groups (P<0.05). In this study, compared with clinically healthy dogs, significant increases in serum cTnI, cTnT, LDH and CK-MB concentrations were detected in dogs with CMVD. The findings of this study indicate that the biochemical markers activity elevated with severity of the disease in dogs with CMVD. Measurement of cardiac troponins, as the newer markers than LDH and CK-MB concentrations, may be useful in the detection of cardiac injury and prognosis in dogs with CMVD.

Remote Ischemic Preconditioning Reduces Cardiac Troponin I Release in Cardiac Surgery: A Meta-Analysis

We present two cases with clearly discrepant results of clinical examination and cardiac troponin I (cTnI) and cardiac troponin T (cTnT) concentrations. In similar cases with discrepant results, the possibility of interference should be considered. Due to the suspicion of the presence of macrotroponin I in both of the presented cases, the patients were invited to our laboratory and both cTnI (Architect i1000, Abbott) and cTnT (Cobas 8000, Roche) concentrations were analysed. The samples were treated by preincubation in a heterophilic antibodies blocking tube (HBT) and analysed. Precipitation with polyethylene glycol solution (PEG) and molecular weight separation by gel filtration on Sephadex G100 was performed and concentrations of cTnI were analysed. In the same blood sample, the cTnT and cTnI concentrations were 7 and 1782 ng/L, respectively, in Case 1, and 6 and 96 ng/L, respectively, in Case 2. Incubation of samples in HBT had no significant effect. CTnI concentrations after precipitation with PEG - presented as the percentage of initial concentrations - were 7.4% in Case 1 (and 26.8% in the control sample) and 1.4% in Case 2 (and 56.0% in the control sample). These results indicate a significant decrease in both cases, supporting presence of macrotroponin I. Finally, analyses of cTnI concentrations after gel filtration also supported the presence of macrotroponin I. The present cases show that the presence of macrotroponin can lead to unnecessary investigation of the patient. When the possibility of interference is suspected, cooperation with laboratory staff to help with interpretation or to perform more detailed analysis is crucial.

Background Clinical practice and guidelines assume that cardiac troponin I (cTnI) and cTnT are interchangeable, reflecting identical pathophysiological processes. However, it is unknown if cTnI and cTnT really are equivalent measures in different pathophysiological settings. Purpose To highlight potential differences in the release of cTnI and cTnT. Methods Large pooled cohort analysis including extensively characterized individuals, stratified into three groups: no cardiac disease (normal aging), chronic cardiac disease, and acute cardiac disease. Circulating cTnI and cTnT concentrations were measured blinded to clinical data using high-sensitivity assays (hs-cTnI-Architect, hs-cTnT-Elecsys) and their ratio calculated. Findings were validated using a second hs-cTnI assay (hs-cTnI-Clarity). Results Among 8719 individuals, 29% female, 10% had no known cardiac disease, 71% chronic cardiac disease, and 20% acute cardiac disease. Baseline characteristics including renal function were comparable between individuals with chronic and acute cardiac disease. Normal aging (without cardiac disease) was associated with a disproportional increase in cTnT versus cTnI (low cTnI/cTnT ratio, median 0.50, IQR 0.38–0.68). Although older, patients with chronic cardiac disease had a slightly higher cTnI/cTnT ratio (median 0.53, IQR 0.37–0.79, p&amp;lt;0.05). In contrast, in patients with acute cardiac disease, cTnI concentrations were disproportionally elevated compared to cTnT concentrations, resulting in a cTnI/cTnT ratio of 1.96 (IQR 0.93–4.73, p&amp;lt;0.001). Internal validation using a second hs-cTnI assay confirmed these findings. Conclusion These findings suggest relevant differences in the release of cTnI and cTnT with a greater release of cTnT versus cTnI in normal aging and a disproportional increase in cTnI versus cTnT in acute cardiac disease. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Swiss National Science Foundation

This study evaluated the effects of exercise on cardiac troponin I (cTnI) concentrations in healthy, adult horses.Fifteen fit, healthy horses determined to have a normal cardiovascular system completed a standardized exercise test on a high-speed treadmill. Heparinized blood was collected for plasma cTnI concentrations before maximal exercise, and 1, 3, 6, 9, 12 and 24 h post-exercise. The cTnI concentrations were measured with a commercial system (Stratus CS, Dade Behring, Inc.). Results were analysed by a multivariate ANOVA, where indicatedpost hocanalysis was done by Tukey–Kramer HSD and significance was placed atp &lt; 0.05.All horses had elevations in cTnI concentrations after maximal exercise. Values for cTnI trended higher at 3 h (0.066 ± 0.011 ng ml− 1) and 6 h (0.062 ± 0.011 ng ml− 1) post-exercise compared with pre-exercise (0.039 ± 0.007 ng ml− 1), although this did not reach statistical significance. Mean cTnI concentrations were within our normal reference range at all time points, although four individuals were above our normal range after exercise.These data show that short-term, high-intensity exercise induces a small rise in plasma cTnI in normal horses. This should be kept in mind when evaluating cTnI concentrations in horses that have recently completed intense exercise. In addition, these data suggest that 3–6 h after intense exercise may be the optimal time for measurement of cTnI concentrations in horses with suspected exercise-induced myocardial damage.

Unusually high concentrations of cTnI and cTnT in a patient with catastrophic antiphospholipid antibody syndrome

Effect of racing on cardiac troponin I concentration and associations with cardiac rhythm disturbances in Standardbred racehorses

To evaluate and compare the clinical usefulness of plasma atrial natriuretic peptide (ANP) and cardiac troponin-I (cTnI) concentrations for assessment of disease severity in dogs with naturally occurring mitral valve disease (MVD). 316 dogs with MVD and 40 healthy control dogs. Each dog underwent a physical examination and echocardiographic and thoracic radiographic assessments. Blood samples were obtained and processed for measurement of plasma ANP and cTnI concentrations. Dogs with MVD were categorized into 3 groups (stages B1 [no clinical signs or evidence of cardiac enlargement], B2 [no clinical signs with evidence of cardiac enlargement], and C [history of congestive heart failure and pulmonary edema]) on the basis of American College of Veterinary Internal Medicine guidelines. Receiver operating characteristic curve analysis was used to evaluate the accuracy of plasma ANP and cTnI concentrations for assessment of MVD severity. Plasma ANP and cTnI concentrations increased as disease severity increased. Median plasma ANP concentrations for all 3 MVD groups and median plasma cTnI concentrations for the stage B2 and C groups were significantly greater than the corresponding concentrations for the control group. Plasma ANP concentration, but not cTnI concentration, appeared to be useful for detection of dogs with subclinical (stages B1 and B2) MVD, whereas both concentrations appeared useful for detection of dogs with stage C MVD. Results indicated that plasma ANP and cTnI concentrations should not be used independently to diagnose MVD but can be used to assess MVD severity and supplement echocardiographic findings.

There is a paucity of information regarding cardiac troponin (cTn) concentrations in peripheral blood of nonhuman primates (NHP). Even less is known regarding cTn concentrations in monkeys that are restrained for oral or intravenous (iv) dosing. The objectives of these studies were to (1) determine cardiac troponin I (cTnI) concentration in resting Cynomolgus monkeys and investigate biologic variability in cTnI concentration over time, (2) determine cTnI changes in restrained monkeys given sham oral dosing, and (3) determine cTnI changes in restrained NHP given a sham intravenous dosing. The Research Use Only Erenna cTnI ultrasensitive immunoassay based on single molecule counting technology was used to determine serum cTnI concentration in longitudinal studies of male Cynomolgus monkeys at rest, and after sham oral and intravenous dosing. Animals were catheterized prestudy, and blood samples were collected by an automated sampling device to limit disturbance of the animals during studies. In resting monkeys cTnI concentrations were relatively low and constant and ranged from 0.2 to 9.6 pg/mL (mean = 2.5 pg/mL), with minimal variability during a 24-hour period. Animals given sham oral dosing also had low cTnI concentration with little variability similar to the resting values. Several animals restrained for intravenous dosing had a small transient increase in cTnI concentration (~5-25 pg/mL) that resolved quickly within one to 3 hours postinjection. Results of this longitudinal study provide information that may be important in differentiating effects of animal handling from those associated with compound-related effects in preclinical toxicology studies of drugs in development.

Concentrations of cardiac troponin I (cTnI) and T (cTnT) are associated with clinical cardiac outcomes, but do not correlate closely in subjects recruited from the general population. Accordingly, we hypothesized that cTnI and cTnT concentrations would be influenced by different cardiovascular (CV) and non-CV risk factors and reflect different CV phenotypes. We measured cTnI and cTnT with last generation assays in 1236 women and 1157 men with no known CV disease participating in the prospective observational Akershus Cardiac Examination 1950 Study. All study participants underwent extensive CV phenotyping at baseline, including detailed echocardiography. Concentrations of cTnI were measurable in 60.3% and cTnT in 72.5% of study participants (P < 0.001), and correlated moderately (r = 0.53; P < 0.001). cTnI was more strongly associated with male sex (P = 0.018), higher education (P < 0.001), history of hypertension (P < 0.001), and age (P < 0.001), whereas cTnT was more strongly associated with eGFR (P = 0.015). Both cTnI and cTnT were inversely associated with global longitudinal strain and positively associated with LV mass index (LVMI) in analyses adjusted for CV risk factors. The association between cTnI and LVMI was stronger than the association between cTnT and LVMI (P = 0.035). Concentrations of cTnI improved diagnostic accuracy for LV hypertrophy when added to established CV risk factors, but concentrations of cTnT did not improve these models further. In a large community-based cohort examined with extensive echocardiography, concentrations of cTnI and cTnT are associated with subclinical LV hypertrophy and dysfunction. Concentrations of cTnI appear superior to cTnT in predicting subclinical LV hypertrophy.

BackgroundCongenital heart disease is a leading cause of death in newborns and infants. The feasibility of fetal cardiac surgery is linked to extracorporeal circulation (ECC); therefore, cardioplegic solutions need to be effective and long-lasting.MethodsEighteen pregnant sheep were divided into an ECC-only group, St. Thomas’ Hospital cardioplegic solution (STH1) group (STH group), and HTK preservation solution (Custodiol®) group (HTK group). Markers of myocardial injury including troponin I (cTnI), troponin T (cTnT) and creatine kinase myocardial band (CKMB) were measured at specific time points (T1: pre-ECC, T2: 30 min of ECC, T3: 60 min of ECC, T4: 60 min post-ECC, T5: 120 min post-ECC). Myocardial tissue was removed from the fetal sheep at T5, and apoptosis was detected by TUNEL staining.ResultsChanges in the serum cTnI, cTnT and CKMB concentrations were not significantly different among the three groups before and during the ECC(T1,T2,T3). At 60 min after ECC shutdown(T4), cTnI and cTnT concentrations were significantly higher in the STH group than before the start of ECC. The concentration of cTnI was higher in the STH group than in the HTK and ECC-only groups. The concentration of cTnT was higher in the STH group than in the ECC-only group. At 120 min after ECC shutdown(T5), cTnI and cTnT concentrations were significantly higher in the ECC and HTK groups than before the start of ECC, and CKMB concentration was significantly higher in STH and HTK groups. The concentrations of cTnT, cTnI and CKMB was higher in the STH group than in the HTK and ECC-only groups. The number of TUNEL-positive cells in the HTK and STH groups was higher than in the ECC-only group. The number of TUNEL-positive cells in the STH group was higher than in the HTK group. There was no statistically significant difference among the groups in the heart rate and mean arterial pressure after ECC.ConclusionThe HTK preservation solution was significantly better than STH1 in reducing the release of cardiomyocyte injury markers and the number of apoptotic cells in fetal sheep ECC. Fetal sheep receiving ECC-only had an advantage in all indicators, which suggests ECC-only fetal heart surgery is feasible.

Cardiac troponin I and the occurrence of cardiac arrhythmias in horses with experimentally induced endotoxaemia

PURPOSE: Cardiac troponins I and T (cTnI, cTnT) and brain natriuretic peptid (BNP) are the accepted standards to serologically identify myocardial necrosis and elevated wall stress. In addition, they allow risk stratification in cardiovascular patients. However, the clinical significance of increases after strenuous endurance-exercise in obviously healthy athletes is unclear. We therefore examined the reproducibility and clinical significance of exercise-induced increases in cTnT, cTnI and NT-proBNP after two standardized endurance exercise-bouts in healthy endurance-athletes with prior competition-induced elevations of cardiac troponins (cTnI: 0.08–1.93ug/L; cTnT: 0.01–0.56ug/L). METHODS: 20 male athletes (36±7 years; VO2max: 60±5 ml/min/kg) completed a 1h and a 3h exercise-study (1HET; 3HET; exercise-intensities: 100%; 75% of the individual anaerobic threshold) on two different days in randomized order to determine cardiac markers before, 30min and 3h after exercise. In addition to pre- and post-exercise echo car diography including Tissue-Doppler-Imaging (TDI), delayed-enhancement magnetic-resonance-imaging (DE-MRI) was performed after 3HET to detect myocardial necrosis. RESULTS: A minimal increase in cTnI was documented after both exercise-trials (0.02 to 0.03 ug/L; p < 0.001). cTnT remained without significant changes. NT-proBNP increased by 15ng/L and 30ng/L after 1HET and 3HET, respectively (p < 0.001). In contrast to cardiac troponins, increases in NT-proBNP after competition correlated with those after 1HET (R=0.88) and 3HET (R=0.82). No pathologies were demonstrated by echocardiography or DE-MRI. CONCLUSIONS: Due to the missing reproducibilty and evidence of myocardial damage, exercise-induced increases in cardiac troponins may represent a physiologic reaction under special conditions and seem to be without pathological significance in healthy athletes. The reproducible increases in NT-proBNP may modulate myocardial hypertrophy in endurance-exercise.

Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Grieg Foundation and Western Norway Regional Health Authority. Background There is a growing evidence that patients with angiographic signs of coronary artery disease should receive preventive therapy to reduce the risk of future adverse cardiac events. Purpose Evaluate whether cardiac troponin T and I (cTnT and cTnI) concentrations within the range from the limit of detection of the assay to the 99th percentile or GDF-15 may help identify patients with angiographic evidence of coronary artery disease (CAD). Methods A subgroup of 550 patients from the WESTCOR study with both cTnT and cTnI concentrations ≤99th percentile was evaluated with coronary computed tomography angiography (CCTA). CAD was defined as ≥10% narrowing of lumen of any coronary artery on CT angiogram or too high calcium score for anatomy to be evaluated. Overall diagnostic accuracy of cTnT, cTnI and GDF-15 and their combination were evaluated calculating the area under the receiver-operating characteristics curve (ROC-AUC). cTn analysis were performed using high-sensitivity assays from Roche Diagnostics (cTnT, limit of detection of 5 ng/L and gender-neutral 99th percentile of 14 ng/L) and Abbott Diagnostics (cTnI, limit of detection 1.6 ng/L and 99th percentile 16 ng/L for women and 34 ng/L for men). GDF-15 analyses were performed using the GDF-15 assay on Cobas e801 (Roche Diagnostics). Results A total of 53.5 percent (294 of 550 patients) had angiographic coronary disease. The risk of having CAD was significantly higher in patients with cTnT between 5 ng/ml and the gender-neutral 99th percentile compared to very low levels of cTnT &amp;lt;5 ng/ml, 65.7% (95% CI: 60-71%) vs 38.1% (95% CI: 32-44%, p-value for difference &amp;lt;0.001). Similar numbers for cTnI between 2 ng/ml and the gender-specific 99th percentile compared to very low levels &amp;lt;2 ng/ml was 62.9% (95% CI: 57-69%) vs 43.2% (95% CI: 37-49%, p-value for difference &amp;lt;0.001). The odds ratio for CAD if cTnT was ≥5 ng/ml or cTnI ≥2 compared to very low levels was 3.1 (2.1-4.4) for cTnT and 2.2 (1.6-3.1) for cTnI. For GDF-15, the risk of having CAD was lower in patients with low values &amp;lt;1200 ng/L (49.7%, 95% CI: 45-54%) compared to patients with higher concentrations &amp;gt;1200 ng/L (75.9%, 95% CI: 66-86%, p-value for difference &amp;lt;0.001). The accuracy of cTnT was significantly higher than for cTnI for identifying CAD (AUC 0.67, 95% CI 0.63-0.71 vs. 0.61, 95% CI 0.58-0.66, p-value for difference &amp;lt;0.01), and borderline higher than for GDF-15 (AUC 0.62, p-value for difference 0.067). Adding GDF-15 to cTn did not increase diagnostic performance of cTnT (AUC 0.67 vs. 0.68, p-value for difference 0.56) or cTnI (AUC 0.61 vs. 0.63, p-value for difference 0.23). Conclusion Overall diagnostic performance of cTnT is superior to cTnI in identifying patients without angiographic evidence of CAD. Adding GDF-15 does not increase overall diagnostic performance. Legend: Figure 1. Receiver-operating characteristics curve of cTnT, cTnI and GDF-15 for the identification of CAD (≥10% lumen reduction).