A comparison of modelled serum cTnT and cTnI kinetics after 60 min swimming.

Post-exercise elevations of cardiac troponin T (cTnT) and I (cTnI) are often used in isolation but interpreted interchangeably. Research suggests, however, that post-exercise cTn kinetic might differ with each isoform. In this cross-sectional observational study, we collected blood samples before, immediately after (5 minutes), and at 1-, 3-, 6-, 12-, and 24-hour post-exercise in a mixed cohort of 56 participants after a distance-trial of 60 min continuous swimming (age range from 14 to 22, 57.1% female). Cardiac troponin kinetics were modelled using Bayesian mixed-effects models to estimate time to peak (TTP) and peak concentration (PC) for each isoform, while controlling for participants sex, tanner stage and average relative heart rate during the test. Exercise induced an elevation of cTnT and cTnI in 93% and 75% of the participants, respectively. Cardiac troponin T peaked earlier, at 2.9 h (CI: 2.6 - 3.2 h) post-exercise, whereas cTnI peaked later, at 4.5 h (CI: 4.2 - 4.9 h). Peak concentrations for cTnT and cTnI were 2.5 ng/L, CI: 0 - 11.2 ng/L and 2.16 ng/L, CI: 0 - 22.7 ng/L, respectively. Additionally, we did not observe a systematic effect of sex and maturational status mediating cTn responses.

Frequency histograms of three high-sensitivity cardiac troponin assays in a reference population.

BACKGROUND: Cardiac troponin (cTn) values above the 99th percentile upper reference limit (URL) indicate myocardial injury. We established 99th percentile URLs for three high-sensitivity cTn (hs-cTn) assays (Beckman Coulter Access hs-cTnI, Abbott STAT hs-cTnI, and Roche Elecsys hs-cTnT) using a healthy population in Korea. METHODS: Each cTn value was measured by three assays and analyzed by dividing by gender and age. RESULTS: The frequency histograms of log-transformed cTn values for Beckman and Abbott assays exhibited a bell-shaped distribution. The 99th percentile URLs were 9.8, 17.4, and 17.3 ng/L in the total population; 10.9/9.0, 18.9/17.0, and 18.9/17.7 ng/L in the male/female population (p < 0.001 for all three assays); and 11.2/7.2, 19.9/14.5, and 22.7/9.3 ng/L in the older/younger population (p < 0.001 for all three assays) for Beckman, Abbott, and Roche assays, respectively. CONCLUSION: Among the three assays, bell-shaped distributions were observed in a frequency histogram of log-transformed cTn values for healthy population in Beckman and Abbott assays. Also, our findings show that the 99th percentile URLs for cTn levels vary not only by gender but age.

The cardiovascular disorders and prognostic cardiac biomarkers in COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to the outbreak of coronavirus disease 2019 (COVID-19), a worldwide epidemic disease affecting increasing number of patients. Although the virus primarily targets respiratory system, cardiovascular involvement has been reported in accumulating studies. In this review, we first describe the cardiac disorders in human with various types of CoV infection, and in animals infected with coronavirus. Particularly, we will focus on the association of cardiovascular disorders upon SARS-CoV-2 infection, and prognostic cardiac biomarkers in COVID-19. Besides, we will discuss the possible mechanisms underlying cardiac injury resulted from SARS-CoV-2 infection including direct myocardial injury caused by viral infection, reduced level of ACE2, and inflammatory response during infection. Improved understandings of cardiac disorders associated with COVID-19 might predict clinical outcome and provide insights into more rational treatment responses in clinical practice.

Cardiac Troponin I association with critical illness and death risk in 726 seriously ill COVID-19 patients: A retrospective cohort study.

Background: For coronavirus disease 2019 (COVID-19), early identification of patients with serious symptoms at risk of critical illness and death is important for personalized treatment and balancing medical resources. Methods: Demographics, clinical characteristics, and laboratory tests data from 726 patients with serious COVID-19 at Tongji Hospital (Wuhan, China) were analyzed. Patients were classified into critical group (n = 174) and severe group (n= 552), the critical group was sub-divided into survivors (n = 47) and non-survivors (n = 127). Results: Multivariable analyses revealed the risk factors associated with critical illness in serious patients were: Advanced age, high respiratory rate (RR), high lactate dehydrogenase (LDH) level, high hypersensitive cardiac troponin I (hs-cTnI) level, and thrombocytopenia on admission. High hs-cTnI level was the independent risk factor of mortality among critically ill patients in the unadjusted and adjusted models. ROC curves demonstrated that hs-cTnI and LDH were predictive factors for critical illness in patients with serious COVID-19 whereas procalcitonin and D-Dimer with hs-cTnI and LDH were predictive parameters in mortality risk. Conclusions: Advanced age, high RR, LDH, hs-cTnI, and thrombocytopenia, constitute risk factors for critical illness among patients with serious COVID-19, and the hs-cTnI level helps predict fatal outcomes in critically ill patients.

Cardiac Biomarker Abnormalities Are Closely Related to Prognosis in Patients with COVID-19.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is erupting and spreading globally. Cardiovascular complications secondary to the infection have caught notice. This study aims to delineate the relationship of cardiac biomarkers and outcomes in severe cases of corona virus disease 2019 (COVID-19). One hundred forty-eight critically ill adult patients with COVID-19 were enrolled. From these patients, the demographic data, symptoms, cardiac biomarkers, treatments, and clinical outcomes were collected. Data were compared between survivors and non-survivors. Four patients in the non-survivor group were selected, and their cardiac biomarkers were collected and analyzed. Among the 148 patients, the incidence of cardiovascular complications was 19 (12.8%). Five of them were survivors (5.2%), and 14 of them were non-survivors (26.9%). Compared with the survivors, the non-survivors had higher levels of high-sensitivity cardiac troponin I, creatine kinase isoenzyme-MB, myoglobin, and N-terminal pro-brain natriuretic peptide (P < 0.05). The occurrence of cardiovascular events began at 11-15 days after the onset of the disease and reached a peak at 14-20 days. COVID-19 not only is a respiratory disease but also causes damage to the cardiovascular system. Cardiac biomarkers have the potential for early warning and prognostic evaluation in patients with COVID-19. It is recommended that cardiac biomarker monitoring in patients with COVID-19 should be initiated at least from the 11th day of the disease course.

Significant association between admission serum monocyte chemoattractant protein-1 and early changes in myocardial function in patients with first ST-segment elevation myocardial infarction after primary percutaneous coronary intervention.

BACKGROUND: Recent studies have indicated that monocyte chemoattractant protein-1 (MCP-1) plays an important role in the initiation and progression of ischaemic heart disease. However, no previous research has investigated the correlation between serum MCP-1 levels and early changes in myocardial function in patients with ST-segmental elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PCI). METHODS: A total of 87 STEMI patients who had undergone a successful primary PCI were consecutively recruited. All the patients included in this study were grouped into two subgroups according to the median value of MCP-1 upon admission. An early change in left ventricular ejection fraction (LVEF) was defined as (LVEF at 3 months post-STEMI)-(LVEF at 2 days post-STEMI). RESULTS: Serum MCP-1 levels increased gradually over time during the first 72 h after the onset of STEMI. The concentration of hypersensitive cardiac troponin I (hs-cTnI) upon admission as well as at 24 h and 72 h after primary PCI, especially the peak hs-cTnI concentration, declined significantly in the low admission MCP-1 group. As continuous variable, admission MCP-1 also correlated positively with admission hs-cTnI, hs-cTnI at 24 h after primary PCI, and peak hs-cTnI. Additionally, the absolute early change in LVEF improved markedly in the low admission MCP-1 group (3.77% ± 6.05% vs - 0.18% ± 7.69%, p = 0.009) compared to that in the high admission MCP-1 group. Most importantly, the global LVEF in the low admission MCP-1 group also improved significantly at 3 months compared to baseline LVEF (55.79% ± 7.05% vs 59.60% ± 6.51%, p = 0.011), while an improvement in global LVEF was not observed in the high admission MCP-1 group. Furthermore, as a continuous variable, the MCP-1 level up admission also correlated negatively with early changes in LVEF (r = - 0.391, p = 0.001). After assessment by multiple linear regression analysis, the MCP-1 level upon admission remained correlated with early changes in LVEF [beta = - 0.089, 95% CI (- 0.163 to - 0.015), p = 0.020]. CONCLUSION: MCP-1 upon admission not only correlated positively with hs-cTnI at different time points and peak hs-cTnI, but also associated inversely with early improvements in myocardial function in patients with first STEMI. So we speculated that suppression the expression of MCP-1 via various ways may be a promising therapeutic target in myocardial I/R injury in the future.

Serum myeloperoxidase, paraoxonase, and plasma asprosin concentrations in patients with acute myocardial infarction.

Introduction: The objective of this study was to evaluate the usefulness of the serum biomarkers myeloperoxidase (MPO), paraoxonase (PON), and plasma asprosin in acute myocardial infarction (AMI) diagnosis and assess their compatibility with routinely screened cardiac biomarkers. Methods: This study was conducted using a prospective cross-sectional design and included 90 patients, consisting of 60 patients diagnosed with AMI (30 with ST-segment elevation and 30 with non-ST-segment elevation on ECG) and 30 controls (without a diagnosis of AMI). Changes in the levels of cardiac biomarkers (Hs-cTnI, CK, CK-MB), lipid profile (TC, TG, LDL, HDL), MPO, PON, asprosin, and routine biochemical parameters of patients were evaluated. Furthermore, receiver operating characteristic curve analysis revealed the diagnostic value of Hs-cTnI, MPO, PON, and asprosin in predicting AMI. Binary logistic regression analysis of cardiac marker concentrations was used to predict the presence of AMI. In contrast, multinomial logistic regression analysis was conducted to predict the type of AMI and the control group. Results: The median levels of MPO and plasma asprosin were found to be higher in the patient group (3.22 [interquartile range {IQR}: 2.4-4.4] ng/ml and 10.84 [IQR: 8.8-17.8] ng/ml, respectively) than in the control group (2.49 [IQR: 1.9-2.9] ng/ml and 4.82 [IQR: 4.6-8.0] ng/ml, respectively) (p = 0.001 and p < 0.001, respectively). The median levels of PON were 8.94 (IQR: 7.6-10.4) ng/ml in the patient group and 10.44 (IQR: 9.1-20.0) ng/ml in the control group (p < 0.001). In the binary logistic regression model, compared with the control group, a 1 ng/ml increase in MPO level increased the odds of having AMI by 3.61 (p = 0.041, 95% CI: 1.055-12.397), whereas a 1 ng/ml increase in asprosin level increased the odds of having AMI by 2.33 (p < 0.001, 95% CI: 1.479-3.683). In the multinominal logistic regression model, compared with the control group, a 1 ng/ml increase in the MPO level increased the odds of having NSTEMI by 4.14 (p = 0.025, 95% CI: 1.195-14.350), whereas a 1 ng/ml increase in asprosin concentrations increased the odds of having NSTEMI by 2.35 (p < 0.001, 95% CI: 1.494-3.721). Conclusion: Herein, MPO and asprosin concentrations increased with Hs-cTnI, and a decrease in PON concentration indicated that oxidant-antioxidant parameters and adipokines were related to AMI pathogenesis.

Specific reference interval for high-sensitivity cardiac troponin I among healthy children in Wuhan, China.

Background: Troponin (Tn) is of an important biomarker for the diagnosis and prognosis of myocardial injury and for evaluating the severity of cardiac involvement due to other systemic diseases in children. Unfortunately, high-sensitivity cardiac troponin I (hs-cTnI) specific reference intervals (RIs) are extremely limited. This study aimed to establish a preliminary pediatric hs-cTnI RI for newborns, children, and adolescents in Wuhan, China. Methods: A total of 1,355 healthy participants (1 day to 19 years) were recruited from a cross-sectional study implemented in Wuhan Children's Hospital from September 2022 to August 2023. Serum hs-cTnI levels were detected via the Mindray automated chemiluminescence immunoassay analyzer (CL-6000i). Specific serum hs-cTnI RIs were established according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. The RIs were defined by the nonparametric median (P50), and 2.5th, 97.5th [P50 (P2.5-P97.5)] intervals. Results: Of the 1,355 pediatric participants, serum hs-cTnI concentrations of 1,332 children were measured. The serum overall P50 and 95% interval range (P2.5-P97.5) of serum hs-cTnI was 0.41 (0.00, 44.31) ng/L. This was higher in males of 0.47 (0.00, 44.90) ng/L than in females of 0.36 (0.00, 44.17) ng/L (P<0.01). Age- and sex-specific differences in hs-cTnI levels were observed. The levels were highly variable in children under 1 year of age (especially in newborns), deriving a P50 (P2.5-P97.5) of 22.06 (1.04, 154.22) ng/L, and gradually narrowed and decreased with increasing age, with a markedly lower established P50 (P2.5-P97.5) of 0.36 (0.00, 2.16) ng/L. However, the levels began to increase slightly at the age of 9-12 years and reached a small peak at the age range of 15 to 18 years in males with 0.71 (0.03, 3.29) ng/L, while females were less affected by puberty. Sex- and age-specific RIs for hs-cTnI were established: 5 age-specific RIs in males, 1 day-1 month: 30.16 (8.67, 171.81) ng/L; >1-12 months: 13.20 (0.63, 61.91) ng/L; >1-15 years: 0.36 (0.00, 1.86) ng/L; >15-18 years: 0.71 (0.03, 3.29) ng/L; >18-19 years: 0.52 (0.00, 1.92) ng/L; and 4 age-specific RIs in females, 1 day-1 month: 43.93 (18.82, 146.38) ng/L; >1-12 months: 5.22 (0.92, 42.54) ng/L; >1-6 years: 0.54 (0.00, 2.74) ng/L; >6-19 years: 0.23 (0.00, 1.56) ng/L. Conclusions: This study preliminarily established age- and sex-specific serum hs-cTnI RIs using the Mindray CL-6000i system in healthy children in Wuhan, China.

The association of preoperative high-sensitivity cardiac troponin i and long-term outcomes in colorectal cancer patients received tumor resection surgery.

BACKGROUND: This study aimed to evaluate the association between preoperative hs-cTnI and long-term mortality and major adverse cardiovascular events (MACE) in colorectal cancer patients. METHODS: This single-center retrospective cohort study included 1105 consecutive colorectal cancer patients who received tumor resection surgery between January 2018 and June 2020. Inclusion criteria were an age ≥ 18 years and had been tested for hs-cTnI on admission within 7 days prior to tumor resection surgery. Exclusion criteria were emergent surgery, failure to received tumor resection surgery, hospital death, there was clinical evidence of unstable coronary artery disease or pulmonary embolism occurred before operation according to medical record. The primary endpoint was all-cause death. Secondary endpoint was major adverse cardiovascular events (MACE). RESULTS: A total of 1105 patients were enrolled: 1032 with normal hs-cTnI and 73 with elevated hs-cTnI. The mean follow-up was 24.4 ± 10.8 months, 176 patients died and 39 patients met MACE. In the elevated troponin group, 50%, 32.1% and 17.9% died from cancer, cardiovascular and other causes, while those in the normal troponin group were 75.7%, 2% and 22.3%, there was statistical difference between 2 groups (P < 0.001). Patients with elevated preoperative hs-cTnI had significantly higher mortality (P < 0.001) and more MACE (P < 0.001) compared with those with normal hs-cTnI. A propensity-matching analysis were performed, resulting in 151 patients with normal hs-cTnI and 60 patients with elevated hs-cTnI. The matched population had the similar results for all-cause death (P = 0.009) and MACE (P = 0.001). The results were consistent after further excluding 147 patients who had received chemoradiotherapy prior to surgery in subgroup analysis. The results of multivariate Cox regression analysis shown that hs-cTnI was one of the best predictors for all-cause death (hazard ratio [HR] 2.278; 95% confidence interval [CI] 1.19-4.361) and MACE (HR, 3.523; 95%CI, 1.477-8.403) in total populations, similar results were found in subgroup analysis. CONCLUSIONS: Colorectal cancer patients without myocardial ischemia manifestation but with elevated hs-cTnI prior to tumor resection surgery were at increased risk for long-term all-cause death and MACE, irrespective of whether they have received chemoradiotherapy prior to surgery.

Biomarker-based prediction of fatal and non-fatal cardiovascular outcomes in individuals with diabetes mellitus.

AIMS: The role of biomarkers in predicting cardiovascular outcomes in high-risk individuals is not well established. We aimed to investigate benefits of adding biomarkers to cardiovascular risk assessment in individuals with and without diabetes. METHODS AND RESULTS: We used individual-level data of 95 292 individuals of the European population harmonized in the Biomarker for Cardiovascular Risk Assessment across Europe consortium and investigated the prognostic ability of high-sensitivity cardiac troponin I (hs-cTnI), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hs-CRP). Cox-regression models were used to determine adjusted hazard ratios of diabetes and log-transformed biomarkers for fatal and non-fatal cardiovascular events. Models were compared using the likelihood ratio test. Stratification by specific biomarker cut-offs was performed for crude time-to-event analysis using Kaplan-Meier plots. Overall, 6090 (6.4%) individuals had diabetes at baseline, median follow-up was 9.9 years. Adjusting for classical risk factors and biomarkers, diabetes [HR 2.11 (95% CI 1.92, 2.32)], and all biomarkers (HR per interquartile range hs-cTnI 1.08 [95% CI 1.04, 1.12]; NT-proBNP 1.44 [95% CI 1.37, 1.53]; hs-CRP 1.27 [95% CI 1.21, 1.33]) were independently associated with cardiovascular events. Specific cut-offs for each biomarker identified a high-risk group of individuals with diabetes losing a median of 15.5 years of life compared to diabetics without elevated biomarkers. Addition of biomarkers to the Cox-model significantly improved the prediction of outcomes (likelihood ratio test for nested models P < 0.001), accompanied by an increase in the c-index (increase to 0.81). CONCLUSION: Biomarkers improve cardiovascular risk prediction in individuals with and without diabetes and facilitate the identification of individuals with diabetes at highest risk for cardiovascular events.

In this work, the role of cardiac biomarkers measured from blood to predict cardiovascular events and death is tested in individuals of the general population and particularly in those with known diabetes. The work is based on a cooperation of different population studies across Europe and includes more than 90 000 individuals, with more than 6000 having diabetes. We could demonstrate that the determination of three cardiac biomarkers helps to identify individuals at highest risk for cardiovascular events (e.g. myocardial infarction or stroke) and death, despite accounting for known cardiovascular risk factors in these individuals. Therefore, these biomarkers should be considered for routine risk assessment for cardiovascular diseases and could improve the early identification of high-risk individuals, consequently leading to an earlier initiation of preventive therapies.

Cardiac troponin I in healthy Norwegian Forest Cat, Birman and domestic shorthair cats, and in cats with hypertrophic cardiomyopathy.

OBJECTIVES: The aims of this study were to assess the potential associations between the serum cardiac troponin I (cTnI) concentration in healthy cats and feline characteristics, systolic blood pressure, heart rate (HR), echocardiographic measurements and storage time; and to compare cTnI concentrations in healthy cats with concentrations in cats with hypertrophic cardiomyopathy (HCM), with or without left atrial enlargement (LAE) and in cats with HCM, to assess potential associations between cTnI concentration and echocardiographic variables. METHODS: Cardiac TnI was analysed using an Abbott ARCHITECT ci16200 analyser in serum from prospectively included healthy Norwegian Forest Cat (NF; n = 33), Birman (n = 33) and domestic shorthair (DSH; n = 30) cats, and from 39 cats with HCM, with or without LAE. RESULTS: In healthy cats, higher cTnI concentrations were found in Birman cats than in NF cats (P = 0.014) and in neutered male cats than in intact females (P = 0.032). Cardiac TnI was positively associated with HR (P <0.0001). In cats with HCM, cTnI concentration was positively associated with left ventricular wall thickness and with left atrial-to-aortic root ratio (all P ⩽0.010). Cats with HCM had higher cTnI concentrations than healthy cats, and cTnI concentrations were higher in cats with HCM and LAE than in those with HCM without LAE (all P = 0.0003). CONCLUSIONS AND RELEVANCE: Breed and sex may affect serum cTnI concentrations in healthy cats. The cTnI concentration increased with increasing severity of HCM.

Effect of diet change in healthy dogs with subclinical cardiac biomarker or echocardiographic abnormalities.

BACKGROUND: A recent study showed higher high-sensitivity cardiac troponin I (hs-cTnI) concentrations in healthy dogs eating grain-free (GF) compared to those eating grain-inclusive (GI) diets. HYPOTHESIS/OBJECTIVES: Healthy dogs with subclinical cardiac abnormalities eating GF diets at baseline will show improvements in cardiac biomarkers and echocardiographic variables after diet change, whereas healthy dogs eating GI diets at baseline will not improve. ANIMALS: Twenty healthy dogs with subclinical cardiac abnormalities (12 Golden Retrievers, 5 Doberman Pinschers, 3 Miniature Schnauzers). METHODS: This prospective study included dogs with increased hs-cTnI or N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations, or echocardiographic abnormalities. Mixed modeling was used to evaluate echocardiographic, hs-cTnI, and NT-proBNP differences between groups (GF or GI diet at baseline) over time (1 y after diet change). RESULTS: Ten GF and 10 GI dogs were evaluated. There were statistically significant time: group interactions for hs-cTnI (P = .02) and normalized left ventricular internal systolic diameter (LVIDsN; P = .02), with GF dogs showing larger decreases in these variables than GI dogs. Median (range) hs-cTnI (ng/mL) for GF dogs was 0.141 (0.012-0.224) at baseline and 0.092 (0.044-0.137) at 1 y, and for GI dogs was 0.051 (0.016-0.195) at baseline and 0.060 (0.022-0.280) at 1 y. Median LVIDsN for GF dogs was 1.01 (0.70-1.30) at baseline and 0.87 (0.79-1.24) at 1 y, and for GI dogs was 1.05 (0.84-1.21) at baseline and 1.10 (0.85-1.28) at 1 y. CONCLUSIONS AND CLINICAL IMPORTANCE: Decreased hs-cTnI and LVIDsN in GF dogs after diet change supports reversibility of these subclinical myocardial abnormalities.

Consistency analysis of high-sensitivity cardiac troponin I in peripheral blood and venous blood by quantum dot immunofluorescence assay and clinical application in acute myocardial infarction.

Background: Troponin is an important marker for the diagnosis of acute myocardial infarction (AMI). The detection of troponin in peripheral blood is simpler and more convenient than that in venous blood, which has attracted more and more clinical attention. The purpose of this study is to establish a novel method for the rapid detection of high-sensitivity troponin I (hs-cTnI) in peripheral blood by quantum dot fluorescence immunoassay and evaluated the clinical accuracy of the method. Methods: A total of 90 patients with chest pain admitted to Wuxi Second People's Hospital of Nanjing Medical University had peripheral blood and venous blood samples collected for detection of hs-cTnI by rapid quantum dot fluorescence immunoassay. The differences between the two methods were evaluated, as well as the analytical performance and clinical diagnostic efficacy of hs-cTnI detection by quantum dot fluorescence immunoassay. The final diagnosis was determined by two independent cardiologists. Results: This study verified the precision, linear range and sensitivity of the novel detection method. There was good correlation between the results of hs-cTnI quantum dot fluorescence immunoassay for peripheral blood and the results for venous blood (regression equation Y=1.026x+0.521, R2=0.9337); 94.4% (85/90) of the data were within the conformance limit. In addition, in the analysis of 52 patients with confirmed AMI, the clinical specificity of the quantum dot fluorescence immunoassay in peripheral blood was the same as that in venous blood samples (89.5%:89.5%). Finally, the area under the receiver operating characteristic (ROC) curve of the peripheral blood quantum dot fluorescence immunoassay was 0.9352, the 95% confidence interval (CI) was 0.8829 to 0.9876, the cut-off value was 1.598, and the sensitivity was 82.69%, which was not significantly different from the venous blood method (P value =0.089). Conclusions: Rapid detection of hs-cTnI by quantum dot fluorescence immunoassay in peripheral blood is feasible. It has a high correlation and consistency with the venous blood method, as well as a high clinical diagnostic value for AMI and is more convenient and easier to detect.

Improvement of outcome prediction of hospitalized patients with COVID-19 by a dual marker strategy using high-sensitive cardiac troponin I and copeptin.

BACKGROUND: COVID-19 has been associated with a high prevalence of myocardial injury and increased cardiovascular morbidity. Copeptin, a marker of vasopressin release, has been previously established as a risk marker in both infectious and cardiovascular disease. METHODS: This prospective, observational study of patients with laboratory-confirmed COVID-19 infection was conducted from June 6th to November 26th, 2020 in a tertiary care hospital. Copeptin and high-sensitive cardiac troponin I (hs-cTnI) levels on admission were collected and tested for their association with the primary composite endpoint of ICU admission or 28-day mortality. RESULTS: A total of 213 eligible patients with COVID-19 were included of whom 55 (25.8%) reached the primary endpoint. Median levels of copeptin and hs-cTnI at admission were significantly higher in patients with an adverse outcome (Copeptin 29.6 pmol/L, [IQR, 16.2-77.8] vs 17.2 pmol/L [IQR, 7.4-41.0] and hs-cTnI 22.8 ng/L [IQR, 11.5-97.5] vs 10.2 ng/L [5.5-23.1], P < 0.001 respectively). ROC analysis demonstrated an optimal cut-off of 19.3 pmol/L for copeptin and 16.8 ng/L for hs-cTnI and an increase of either biomarker was significantly associated with the primary endpoint. The combination of raised hs-cTnI and copeptin yielded a superior prognostic value to individual measurement of biomarkers and was a strong prognostic marker upon multivariable logistic regression analysis (OR 4.274 [95% CI, 1.995-9.154], P < 0.001). Addition of copeptin and hs-cTnI to established risk models improved C-statistics and net reclassification indices. CONCLUSION: The combination of raised copeptin and hs-cTnI upon admission is an independent predictor of ICU admission or 28-day mortality in hospitalized patients with COVID-19.

Comparison of ADVIA Centaur ultra-sensitive and high-sensitive assays for troponin I in serum.

Cardiac troponin I (cTnI) is a standard biomarker for the diagnosis of acute myocardial infarction (AMI). While older, ultra-sensitive cTnI (us-cTnI) assays use the 99th percentile as the reference threshold, newer high-sensitive cTnI (hs-cTnI) assays use the limit of detection or functional sensitivity instead. However, little has been done to systematically compare these two methods. The present study also served as a validation of hs-cTnI in our laboratory. Here, we compared the results obtained from the blood serum obtained from 8810 patients using the us-cTnI and the hs-cTnI assays run in tandem on the ADVIA Centaur XP analyser. We found that in 2279 samples the concentration of cTnI measured with the ultra-sensitive method was below the detection limit, while with the high-sensitive method, only 540 were below the detection limit. We also compared results from these assays with the ultimate diagnosis of a subset of individuals. The analysis of the results below cut-off with the ultra-sensitive method showed that this method would not detect 96 cases related to heart disorder. Overall, the main finding of our research is that hs-cTnI is the preferable option and is able to be deployed effectively in the laboratory setting.

[Current characteristics of methods for determining cardiac troponins and their diagnostic value: a mini-review] / Característica actual de los métodos para la determinación de troponinas cardíacas y su valor diagnóstico: minirrevisión.

The expansion and discovery of new diagnostic possibilities for the use of many biomarkers of cardiovascular diseases (CVDs), including cardiospecific troponin isoforms (cTnI, cTnT), is due to improved laboratory methods for their determination. Throughout a long history of the creation and improvement of immunochemical methods for the determination of cTnI and cTnT, significant changes were observed in the concept of biology and its diagnostic value as CVD biomarkers. The obsolete methods of detection of cTnI, cTnT, named low sensitivity and moderate, were distinguished by a relatively low sensitivity, which led to the confirmation late in the diagnosis of acute myocardial infarction (AMI) and, therefore, such methods were gradually replaced by new methods of high and moderate sensitivity, such as definitions of methods, ultra-sensitive (hs-cTnI, hs-cTnT). With the introduction of hs-cTnI and hs-cTnT in clinical practice, the possibility of early diagnosis and exclusion of AMI through the evaluation of the kinetics of the concentration of hs-cTnI and hs-cTnT in the first hours (0-1 hour, 0-2 hours, 0-3 hours) from the moment the patient enters the emergency room. In addition, some of our ideas about the biology of cardiac troponins have changed, and promising new opportunities for their use in medicine have emerged. This manuscript analyzes the key analytical characteristics of hs-cTnI and hs-cTnT detection methods compared to moderately sensitive methods, and reports on new biological data and some new diagnostic possibilities for the use of hs-cTnI and hs-cTnT in modern clinical practice.

La expansión y el descubrimiento de nuevas posibilidades de diagnóstico para el uso de muchos biomarcadores de enfermedades cardiovasculares (ECV), incluidas las isoformas de troponina cardioespecíficas (cTnI, cTnT), se debe a la mejora de los métodos de laboratorio para su determinación. A lo largo de una prolongada historia de la creación y mejora de métodos inmunoquímicos para la determinación de cTnI y cTnT, se observaron cambios significativos en el concepto de biología y su valor diagnóstico como biomarcadores de ECV. Los métodos obsoletos de detección de cTnI, cTnT, llamados de sensibilidad baja y moderada, se distinguieron por una sensibilidad relativamente baja, lo que llevó a la confirmación tardía del diagnóstico de infarto agudo de miocardio (IAM) y, por lo tanto, dichos métodos fueron reemplazados gradualmente por nuevos métodos de alta y moderada sensibilidad, como definiciones de métodos ultrasensibles (hs-cTnI, hs-cTnT). Con la introducción de hs-cTnI y hs-cTnT en la práctica clínica, la posibilidad de diagnóstico precoz y exclusión del IAM mediante la evaluación de la cinética de la concentración de hs-cTnI y hs-cTnT en las primeras horas (0-1 hora, 0-2 horas, 0-3 horas) desde el momento en que el paciente ingresa a urgencias. Además, algunas de nuestras ideas sobre la biología de las troponinas cardíacas han cambiado, y han surgido nuevas oportunidades prometedoras para su uso en medicina. En este artículo se discuten las características analíticas clave de los métodos de detección de hs-cTnI y hs-cTnT en comparación con métodos moderadamente sensibles, e informa sobre nuevos datos biológicos y algunas nuevas posibilidades de diagnóstico para el uso de hs-cTnI y hs-cTnT en la práctica clínica moderna.

Cardiac Troponins: Contemporary Biological Data and New Methods of Determination.

Laboratory diagnosis plays one of the key roles in the diagnosis of many diseases, including cardiovascular diseases (CVD). The methods underlying the in vitro study of many CVD biomarkers, including cardiac troponins (cTnI and cTnT), are imperfect and are continually being improved to enhance their analytical performance, with sensitivity and specificity being the most important. Recently developed improved cTnI and cTnT detection methods, referred to as highly sensitive methods (hs-cTnI, hs-cTnT), have changed many of our ideas about the biology of cardiac troponins and opened up a number of additional diagnostic capabilities for practical healthcare. This article systematizes some relevant data on the biology of cardiac troponins as well as on methods for determining cTnI and cTnT with an analysis of the diagnostic value of their analytical characteristics (limit of blank, limit of detection, 99th percentile, coefficient of variation, and others). Data on extracardiac expression of cTnI and cTnT, mechanisms of formation and potential clinical significance of gender, age, and circadian characteristics of hs-cTnI and hs-cTnT content in serum are discussed. Considerable attention is paid to the discussion of new diagnostic capabilities of hs-cTnI, hs-cTnT, including consideration of promising possibilities for their study in biological fluids that can be obtained by non-invasive methods. Also, some possibilities of using hs-cTnI and hs-cTnT as prognostic laboratory biomarkers in healthy people (for example, to assess the risk of developing CVD) and in patients suffering from a number of pathological conditions that cause damage to cardiomyocytes are examined, and the potential mechanisms underlying the increase in hs-cTnI and hs-cTnT are discussed.

SARS-CoV-2 Viral Load and Myocardial Injury: Independent and Incremental Predictors of Adverse Outcome.

To evaluate the association of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) initial viral load (iVL) and the incidence of myocardial injury (MCI) in hospitalized patients with SARS-CoV-2 infection, we conducted a retrospective longitudinal study of hospitalized patients who had a nasopharyngeal swab sample on admission that returned a positive result for SARS-CoV-2 by polymerase chain reaction between April 4 and June 5, 2020. The cycle threshold (Ct) value was used as a surrogate for the iVL level, with a Ct level of 36 or less for elevated iVL and greater than 36 for low iVL. Myocardial injury was defined as an elevated high-sensitivity cardiac troponin I level that was higher than the 99th percentile upper reference limit. A total of 270 patients were included. Of these, 171 (63.3%) had an elevated iVL and 88 (32.6%) had MCI. There was no significant difference in the incidence of MCI in patients with low iVL compared to those with elevated iVL (28 of 99 [28.3%] vs 60 of 171 [35.1%]; P=.25). In a multivariable model, MCI (odds ratio, 3.86; 95% CI, 1.80 to 8.34; P<.001) and elevated iVL (odds ratio, 4.21; 95% CI, 2.06 to 8.61; P<.001) were independent and incremental predictors of in-hospital mortality. The SARS-CoV-2 iVL level is not associated with increased incidence of MCI, although both parameters are strong independent and incremental predictors of mortality. Understanding the MCI mechanisms allows for early focused interventions to improve survival, especially in patients with SARS-CoV-2 infection and high iVL.

Evaluation of the new Beckman Coulter Access hsTnI: 99th percentile upper reference limits according to age and sex in the Korean population.

BACKGROUND: Defining the 99th percentile upper reference limits (URL) of cardiac troponin I (cTnI) is critical because it is clinically important in determining myocardial injury, and is variable among reagents, age, sex, or races. The analytical performance of the new, high- sensitivity reagent Beckman Coulter Access hsTnI was evaluated, and its 99th percentile URL was determined in the Korean population. METHODS: Analytical performances of Access hsTnI assay were evaluated including imprecision and limit of measurements. To define the reference limits, 600 healthy subjects were included with similar proportions of sex and age groups. RESULTS: Beckman Coulter Access hsTnI assay presented a limit of blank, detection, and quantitation at 10% CV of 0.32 ng/L, 0.63 ng/L, and 6.1 ng/L, respectively, and 98.3% of the healthy population showed cTnI above the limit of detection. The 99th percentile URLs were 9.5 ng/L (90% CI 7.4-14.9), 7.8 ng/L (90% CI 5.5-19.2 ng/L), and 11.3 ng/L (90% CI 8.0-15.7 ng/L) in 600 healthy participants, 300 women and 300 men, respectively with imprecision less than 10% CV. The median values and 99th percentile URLs of hsTnI were higher in men and the age group ≥50 years than in women and the age group <50 years, respectively. CONCLUSIONS: Access hsTnI assay met the performance criteria of the IFCC for high-sensitivity cTnI assays. Their 99th percentile URLs in the Korean population were lower than the manufacturer's claims. cTnI values were significantly different among different sex and age groups.