99th Percentile Upper Reference Limit Research Articles

Analytical validation of the Mindray CL1200i analyzer high sensitivity cardiac troponin I assay: MERITnI study.

This study performed an analytical validation study of the Mindray high-sensitivity cardiac troponin I (hs-cTnI) assay addressing limit of blank (LoB), limit of detection (LoD), precision, linearity, analytical specificity and sex-specific 99th percentile upper reference limits. LoB, LoD, precision, linearity and analytical specificity were studied according to Clinical and Laboratory Standards Institute. We used one reagent lot and one CL1200i analyzer. Skeletal troponin I and T, cardiac troponin T, troponin C, actin, tropomyosin, myosin light chain, myoglobin and creatine kinase (CK-MB) were studied for cross-reactivity. Interference with biotin was examined. Lithium heparin samples (one freeze thaw cycle) from healthy males and females were measured to determine the 99th percentiles by using the non-parametric method. Analyses were performed before and after excluding subjects with clinical conditions and/or increased surrogate biomarkers. The Mindray hs-cTnI assay met criteria to be considered as a hs-cTn assay. LoB and LoD was <0.1 ng/L and 0.1 ng/L, respectively. Repeatability had a coefficient of variation 1.2-3.8 %, and within-laboratory imprecision 1.7-5.0 %. The measuring interval ranged from 1.1 to 28,180 ng/L. The analytical specificity was clinically acceptable for the interferents studied. After exclusions, the 99th percentile URLs obtained were 10 ng/L overall, 5 ng/L for females and 12 ng/L for males. Analytical observations of the Mindray hs-cTnI assay demonstrated excellent LoB, LoD, precision, linearity and analytical specificity, that were in alignment with the manufacturer's claims and regulatory guidelines for hs-cTnI. The assay is suitable for clinical investigation for patient-oriented studies.

DANSPOT: A Multicenter Stepped-Wedge Cluster-Randomized Trial of the Reclassification of Acute Myocardial Infarction: Rationale and Study Design.

Cardiac troponins are the preferred biomarkers for the diagnosis of acute myocardial infarction. Although sex-specific 99th percentile thresholds of troponins are recommended in international guidelines, the clinical effect of their use is poorly investigated. The DANSPOT Study (The Danish Study of Sex- and Population-Specific 99th percentile upper reference limits of Troponin) aims to evaluate the clinical effect of a prospective implementation of population- and sex-specific diagnostic thresholds of troponins into clinical practice. This study is a nationwide, multicenter, stepped-wedge cluster-randomized trial of the implementation of population- and sex-specific thresholds of troponins in 22 of 23 clinical centers in Denmark. We established sex-specific thresholds for 5 different troponin assays based on troponin levels in a healthy Danish reference population. Centers will sequentially cross over from current uniform manufacturer-derived thresholds to the new population- and sex-specific thresholds. The primary cohort is defined as patients with symptoms suggestive of acute coronary syndrome having at least 1 troponin measurement performed within 24 hours of arrival with a peak troponin value between the current uniform threshold and the new sex-specific female and male thresholds. The study will compare the occurrence of the primary outcome, defined as a composite of nonfatal myocardial infarction, unplanned revascularization, and all-cause mortality within 1 year, separately for men and women before and after the implementation of the new sex-specific thresholds. The DANSPOT Study is expected to show the clinical effects on diagnostics, treatment, and clinical outcomes in patients with myocardial infarction of implementing sex-specific diagnostic thresholds for troponin based on a national Danish reference population. URL: https://www.clinicaltrials.gov; Unique identifier: NCT05336435.

Age- and sex-specific 99th percentile upper reference limits for high-sensitivity cardiac troponin T in Chinese older people: Real-world data mining

BackgroundThis study aims to investigate the impact of age and sex on high-sensitivity cardiac troponin T (hs-cTnT) and establish 99th percentile upper reference limits (URLs) in older individuals utilizing large-scale real-world data. Methods40,530 outpatient hs-cTnT results were obtained from the laboratory database from January 1, 2018, to December 31, 2023. Our study included 4,199 elderly outpatients (aged ≥ 60) without cardiovascular disease or other heart-related chronic conditions. Nested analysis of variance was used to explore the necessity of partitioning reference intervals (RIs) by sex and age groups. RIs were established by the refineR algorithm and assessed based on ≤ 10% test results of validation data set outside the new RIs. ResultsRIs for hs-cTnT in the older population needed to be partitioned by sex and age groups ([standard deviation ratio] SDRage = 0.75; SDRsex = 0.49). URLs in older Chinese adults were 21.8 ng/L for males, 16.5 ng/L for females, and 20.7 ng/L for the overall participant group. URLs for males aged 60–69, 70–79, and ≥ 80 were 13.7, 19.4, and 31.0 ng/L, respectively. Female values were 10.1, 17.2, and 22.0 ng/L. Importantly, manufacturer-reported RIs do not suffice for Chinese individuals aged ≥ 70. Validation data showed that 2.7–5.2% of test results fell outside the new RIs, confirming the validity of the results. ConclusionThis study establishes age- and sex-specific 99th percentile URLs for hs-cTnT in Chinese older individuals, thereby enhancing the accuracy of clinical assessments.

Exercise-induced cardiac troponin elevations and cardiac ventricular dysfunction assessed by tissue Doppler echocardiography and speckle tracking among non-elite runners in Beijing marathon

ObjectivesWe aimed to identify the major determinants of cardiac troponin changes response to exercise among non-elite runners participating in the Beijing 2022 marathon, with a particular focus on the associations with the cardiac function assessed by tissue Doppler echocardiography and speckle tracking. DesignA prospective study. MethodsA total of 33 non-elite participants in the 2022 Beijing Marathon were included in the study. Echocardiographic assessment and blood sample collection were conducted before, immediately after, and two weeks after the marathon. Blood samples were analyzed using the same Abbot high-sensitivity cTnI STAT assay. Echocardiography included tissue Doppler and speckle tracking echocardiography. ResultsFollowing the marathon, significant increases were observed in cardiac biomarkers, with hs-cTnI elevating from 3.1 [2.3–6.7] to 49.6 [32.5–76.9] ng/L (P < 0.0001). Over 72 % of participants had post-race hs-TnI levels surpassing the 99th percentile upper reference limit. There was a notable correlation between pre-marathon hs-cTnI levels (β coefficient, 0.56 [0.05, 1.07]; P = 0.042), weekly average training (β coefficient, −1.15 [−1.95, −0.35]; P = 0.009), and hs-cTnI rise post-marathon. Echocardiography revealed significant post-race cardiac function changes, including decreased E/A ratio (P < 0.0001), GWI (P < 0.0001), and GCW (P < 0.0001), with LVEF (β coefficients, 0.112 [0.01, 0.21]; P = 0.042) and RV GLS (β coefficients, 0.124 [0.01, 0.23]; P = 0.035) changes significantly associated with hs-TnI alterations. All echocardiographic and laboratory indicators reverted to baseline levels within two weeks. ConclusionsBaseline hs-cTnI levels and weekly average training influence exercise-induced hs-cTnI elevation in non-elite runners. Echocardiography revealed post-race changes in cardiac function, with LVEF and RV GLS significantly associated with hs-TnI alterations. These findings contribute to understanding the cardiac response to exercise and could guide training and recovery strategies.

Myocardial injury after orbital atherectomy and its association with coronary lesion length

BackgroundLimited data are available regarding myocardial injury and its risk factors in percutaneous coronary interventions (PCI) of severe calcified lesions using orbital atherectomy (OA). MethodsPatients who underwent OA at our institution were retrospectively enrolled into the present registry. High-sensitive Troponin I (hsTroponin I), EKG and echocardiography were used to assess myocardial injury after the procedure. ResultsA total of 27 patients between who underwent OA between January 2022 and June 2023 were included. Myocardial injury (elevation of hsTroponin I above the 99th percentile upper reference limit) occurred in all patients. Median hsTroponin I on the first day after the procedure was 1093 (557–4037) ng/l with a minimum of 86 ng/l and a maximum of 25,756 ng/l. Myocardial infarction occurred in two patients (7 %), who had severe coronary dissection after OA. Lesions were longer (47 [38–52] mm vs. 20 [14–47] mm; p = 0.009) in patients with hsTroponin I levels above the median compared to those with levels below. Furthermore, a moderate correlation between hsTroponin I and lesion length was detected (r = 0.54; p = 0.004). ConclusionsIn the present study myocardial injury occurred in all patients after OA without loss of viable myocardium in the majority of patients. Lesions length was found to be a significant factor associated with markedly increased hsTroponin I after the OA procedure.

High-Sensitivity Cardiac Troponin T and Frailty Predict Short-Term Mortality in Patients ≥75 Years Undergoing Emergency Abdominal Surgery: A Prospective Observational Study.

An elevated cardiac troponin concentration is a prognostic factor for perioperative cardiac morbidity and mortality. In elderly patients undergoing emergency abdominal surgery, frailty is a recognized risk factor, but little is known about the prognostic value of cardiac troponin in these vulnerable patients. Therefore, we investigated the prognostic significance of elevated high-sensitivity cardiac troponin T (hs-cTnT) concentration and frailty in a cohort of elderly patients undergoing emergency abdominal surgery. We included consecutive patients ≥75 years of age who presented for emergency abdominal surgery, defined as abdominal pathology requiring surgery within 72 hours, in a university hospital in Norway. Patients who underwent vascular procedures or palliative surgery for inoperable malignancies were excluded. Preoperatively, frailty was assessed using the Clinical Frailty Scale (CFS), and blood samples were measured for hs-cTnT. We evaluated the predictive power of CFS and hs-cTnT concentrations using receiver operating characteristic (ROC) curves and Cox proportional hazard regression with 30-day mortality as the primary outcome. Secondary outcomes included (1) a composite of 30-day all-cause mortality and major adverse cardiac event (MACE), defined as myocardial infarction, nonfatal cardiac arrest, or coronary revascularization; and (2) 90-day mortality. Of the 210 screened and 156 eligible patients, blood samples were available in 146, who were included. Troponin concentration exceeded the 99th percentile upper reference limit (URL) in 83% and 89% of the patients pre- and postoperatively. Of the participants, 53% were classified as vulnerable or frail (CFS ≥4). The 30-day mortality rate was 12% (18 of 146). Preoperatively, a threshold of hs-cTnT ≥34 ng/L independently predicted 30-day mortality (hazard ratio [HR] 3.14, 95% confidence interval [CI], 1.13-9.45), and the composite outcome of 30-day mortality and MACE (HR 2.58, 95% CI, 1.07-6.49). In this model, frailty (continuous CFS score) also independently predicted 30-day mortality (HR 1.42, 95% CI, 1.01-2.00) and 30-day mortality or MACE (HR 1.37, 95% CI, 1.02-1.84). The combination of troponin and frailty, 0.14 × hs-cTnT +4.0 × CFS, yielded apparent superior predictive power (area under the receiver operating characteristics curve [AUC] 0.79, 95% CI, 0.68-0.88), compared to troponin concentration (AUC 0.69, 95% CI, 0.55-0.83) or frailty (AUC 0.69, 95% CI, 0.57-0.82) alone. After emergency abdominal surgery in elderly patients, increased preoperative troponin concentration and frailty were independent predictors of 30-day mortality. The combination of increased troponin concentration and frailty seemed to provide better prognostic information than troponin or frailty alone. These results must be validated in an independent sample.

A study of clinical and serological correlation of early myocardial injury in elderly patients infected with the Omicron variant.

Myocardial injury in elderly Omicron variant patients is a leading cause of severe disease and death. This study focuses on elucidating the clinical characteristics and potential risk factors associated with myocardial injury in elderly patients infected with the Omicron variant. Myocardial injury was defined based on elevated cardiac troponin concentrations exceeding the 99th percentile upper reference limit. Among 772 elderly Omicron-infected patients, categorized into myocardial injury (n = 263) and non-myocardial injury (n = 509) groups. The stratified log-rank statistic was used to compare the probability of patients developing intensive care. Receiver operating characteristic curves were used to determine the best cut-off values of clinical and laboratory data for predicting myocardial injury. Univariate and multivariate logistic regression was adopted to analyze the risk factors for myocardial injury. The occurrence of myocardial injury in Omicron variant-infected geriatric patients was up to 34.07% and these patients may have a higher rate of requiring intensive care (P < 0.05). By comparing myocardial injury patients with non-myocardial injury patients, notable differences were observed in age, pre-existing medical conditions (e.g., hypertension, coronary heart disease, cerebrovascular disease, arrhythmia, chronic kidney disease, and heart failure), and various laboratory biomarkers, including cycle threshold-ORF1ab gene (Ct-ORF1ab), cycle threshold-N gene (Ct-N), white blood cell count, neutrophil (NEUT) count, NEUT%, lymphocyte (LYM) count, LYM%, and D-dimer, interleukin-6, procalcitonin, C-reactive protein, serum amyloid A, total protein, lactate dehydrogenase, aspartate aminotransferase, glomerular filtration rate, blood urea nitrogen, and serum creatinine (sCr) levels (P < 0.05). Furthermore, in the multivariable logistic regression, we identified potential risk factors for myocardial injury in Omicron variant-infected elderly patients, including advanced age, pre-existing coronary artery disease, interleukin-6 > 22.69 pg/ml, procalcitonin > 0.0435 ng/ml, D-dimer > 0.615 mg/L, and sCr > 81.30 μmol/L. This study revealed the clinical characteristics and potential risk factors associated with myocardial injury that enable early diagnosis of myocardial injury in Omicron variant-infected elderly patients, providing important reference indicators for early diagnosis and timely clinical intervention.

Imprecision of high-sensitivity cardiac troponin assays at the female 99th-percentile

BackgroundAn analytical benchmark for high-sensitivity cardiac troponin (hs-cTn) assays is to achieve a coefficient of variation (CV) of ≤ 10.0 % at the 99th percentile upper reference limit (URL) used for the diagnosis of myocardial infarction. Few prospective multicenter studies have evaluated assay imprecision and none have determined precision at the female URL which is lower than the male URL for all cardiac troponin assays. MethodsHuman serum and plasma matrix samples were constructed to yield hs-cTn concentrations near the female URLs for the Abbott, Beckman, Roche, and Siemens hs-cTn assays. These materials were sent (on dry ice) to 35 Canadian hospital laboratories (n = 64 instruments evaluated) participating in a larger clinical trial, with instructions for storage, handling, and monthly testing over one year. The mean concentration, standard deviation, and CV for each instrument type and an overall pooled CV for each manufacturer were calculated. ResultsThe CVs for all individual instruments and overall were ≤ 10.0 % for two manufacturers (Abbott CVpooled = 6.3 % and Beckman CVpooled = 7.0 %). One of four Siemens Atellica instruments yielded a CV > 10.0 % (CVpooled = 7.7 %), whereas 15 of 41 Roche instruments yielded CVs > 10.0 % at the female URL of 9 ng/L used worldwide (6 cobas e411, 1 cobas e601, 4 cobas e602, and 4 cobas e801) (CVpooled = 11.7 %). Four Roche instruments also yielded CVs > 10.0 % near the female URL of 14 ng/L used in the United States (CVpooled = 8.5 %). ConclusionsThe number of instruments achieving a CV ≤ 10.0 % at the female 99th-percentile URL varies by manufacturer and by instrument. Monitoring assay precision at the female URL is necessary for some assays to ensure optimal use of this threshold in clinical practice.

Impact of the ESC Cardio-Oncology Guidelines Biomarker Criteria on Incidence of Cancer Therapy–Related Cardiac Dysfunction

BackgroundThe impact of recent consensus definitions of cancer therapy–related cardiac dysfunction (CTRCD) from the European Society of Cardiology cardio-oncology guidelines on the reported incidence of CTRCD has not yet been assessed. ObjectivesThe aim of this study was to assess the: 1) cumulative incidence; 2) point prevalence during and after adjuvant therapy; and 3) prognostic value of CTRCD as defined by different asymptomatic CTRCD guideline criteria. MethodsThe cumulative incidence and point prevalence of CTRCD were retrospectively assessed in 118 patients participating in the PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) trial. Asymptomatic CTRCD was assessed using alternative cardiac troponin (cTn) 99th percentile upper reference limits (URLs) to define cTnT and cTnI elevation. ResultsThe cumulative incidence of moderate or severe CTRCD was low (1.7%), whereas the cumulative incidence of mild asymptomatic CTRCD was higher and differed markedly according to the biomarker criteria applied, ranging from 49.2% of patients when cTnT greater than the sex-specific 99th percentile URL was used to define cTn elevation to 9.3% when sex-neutral cTnI was used. The point prevalence of CTRCD was highest at the end of anthracycline therapy (47.8%) and was driven primarily by asymptomatic cTn elevation. CTRCD during adjuvant therapy was not prognostic for CTRCD at extended follow-up of 24 months (Q1-Q3: 21-29 months) after randomization. ConclusionsMild asymptomatic CTRCD during adjuvant breast cancer therapy was frequent and driven mainly by cTn elevation and was not prognostic of subsequent CTRCD. The incidence of mild, asymptomatic CTRCD differed markedly depending on the cTn assay and whether sex-neutral or sex-dependent URLs were applied. (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy [PRADA]; NCT01434134)

Analytical evaluation of the novel Mindray high sensitivity cardiac troponin I immunoassay on CL-1200i.

The current study was designed to evaluate the analytical performance of the new Mindray highly sensitive cardiac troponin I (hs-cTnI) chemiluminescent immunoassay on Mindray CL-1200i, as a thorough validation of novel hs-cTnI methods is required before introduction into clinical practice. The evaluation of the analytical performance of this hs-cTnI immunoassay encompassed the calculation of the limit of blank (LOB), limit of detection (LOD), functional sensitivity, imprecision, linearity, 99th percentile upper reference limit (URL) and concordance with another previously validated hs-cTnI chemiluminescent immunoassay. The LOB and LOD were 0.32 and 0.35 ng/L, whilst the functional sensitivity (expressed as cTnI value with <10 % imprecision), was 0.35 ng/L. The linearity was excellent throughout a wide range of clinically measurable values (r=1.00 between 0.8 and 9,726.9 ng/mL). The intra-assay, inter-assay and total imprecision were 1.1-1.3 %, 5.5-8.1 % and 5.6-8.2 %, respectively. The 99th percentile URL calculated using residual plasma from 246 ostensibly healthy blood donors was 9.2 ng/L (4.3 ng/L in women vs. 12.3 ng/L in men). The Spearman's correlation between Mindray hs-cTnI and Access hs-TnI was 0.97, with mean bias of 7.2 % (95 % CI, 2.6-11.9 %). Although we failed to confirm the very optimistic analytical characteristics previously reported for this method, our evaluation of the novel Mindray hs-cTnI immunoassay on CL-1200i demonstrated that the overall performance is comparable to that of other commercially available hs-cTnI techniques, making it a viable alternative to other methods.

High-Sensitivity Cardiac Troponin and the Management of Congenital Heart Disease in Newborns and Infants.

Early cardiac interventions in newborns and infants suspected for congenital heart disease (CHD) decrease morbidity and mortality. After updating current evidence on the use of cardiac troponins (cTn) in the context of CHD for risk stratification at early ages, we discuss relevant issues, starting from the evidence that only the measurement of the cTnT form is useful in this population. In newborns/infants with CHD, the cTnT concentration increase is correlated with: (a) cardiac stress and hemodynamic parameters, but not with the type of CHD; (b) volume overload/right ventricular pressure overload; (c) postoperative hypoperfusion injury and mortality; and (d) effects of cardioprotective strategies. For infants with CHD, high-sensitivity cTnT (hs-cTnT) concentrations >25 ng/L are an independent predictor of poor outcomes. Transitioning from cTnT to hs-cTnT in newborns/infants improves the identification of: (a) physiopathological mechanisms and factors that increased hs-cTnT early after birth; (b) myocardial injury, even when subclinical; (c) identification of patients requiring immediate therapeutic interventions; and (d) 99th percentile upper reference limits (URLs). However, no reliable URLs are currently available to allow the detection of myocardial injury associated with CHD in newborns/infants. Additional data evaluating the clinical value of hs-cTnT in the risk stratification of newborns/infants with CHD who may suffer myocardial injury is needed. Validating the measurement, possibly in amniotic fluid samples, and improving the interpretation of hs-cTnT concentrations in the prenatal period, at birth and within 1 year of age are crucial to change CHD mortality/morbidity trends in the pediatric population.

Evaluation of analytical and clinical performance of the AFIAS Tn-I plus assay - a new point-of-care

Background The objective of this evaluation was to determine the analytical and clinical performance of the AFIAS point-of-care (POC) Tn-I Plus assay (Boditech Med Inc). Design and methods Limit of detection (LOD), limit of quantification (LOQ), repeatability, reproducibility, inter- and intra-individual CV were evaluated using the CLSI guidelines. The study was also designed to estimate the 99th percentile upper reference limit (URL) and to assess the diagnostic sensitivity and specificity. Results The precision repeatability CVs were 6.7–8.5% and reproducibility was 7.5–7.6%. The LOD and LOQ were consistent with the manufacturer’s specified values of 0.010 ng/mL and 0.030 ng/mL, respectively. The 99th percentile URLs for males (aged 18–75 years) and females (aged 17–65 years) in serum were 0.0300 ng/mL (7.8% CV) and 0.0239 ng/mL (9.4% CV) respectively. Overall 99th percentile URL was 0.0296 ng/mL (8.2% CV). For the overall apparently healthy population, the percentage of measurable cardiac troponin I (cTn-I) values below the 99th percentile (i.e. 0.0296 ng/mL) and above the assay’s LOD (= 0.010 ng/mL) was 47,68% (391/820 samples). The diagnostic sensitivity and specificity were 100% with 95% CI (97% − 100%) and 95.2% with 95% CI (93.6% − 96.5%), respectively. No significant differences were observed for the diagnosis of acute myocardial infarction (AMI) between AFIAS Tn-I plus and Abbott ARCHITECT High Sensitive Troponin-I. Conclusion The clinical performance of AFIAS Tn-I Plus assay for AMI is comparable to the established Abbott ALINITY STAT High Sensitive Troponin-I. This assay is suitable for routine use in clinical laboratories.

CytogeneticsComparability of Beckman Coulter Access Cardiac Troponin I Assays

Abstract Cardiac troponins (cTn) are the most sensitive and specific biomarkers of myocardial injury. The rise and/or fall of cardiac troponins above the 99th percentile of the upper reference limit (URL) is required in the assessment of acute myocardial infarction. In our institution, high sensitivity troponin I (hsTnI) is performed on four Access 2 Immunoassay Systems and three DXI 800 Access Immunoassay Systems. As a regional medical center, we accept patients from outside hospitals where contemporary cardiac troponin I (cTnI) were performed. The results from different assays and platforms may disagree and lead to incorrect explanation of the results as false rise and/or fall of cTn. To harmonize results among these assays, we analyzed the variation between the two assays of cTnI and hsTnI, and the concordance of same assay hsTnI on different instruments using patient specimens. To investigate the between-method variance, 424 patient specimens with troponin levels ranging from 0-23370 ng/L were used to measure both cTnI and hsTnI on DXI 800 instruments. To investigate the within-method agreement, 43 patient specimens with troponin levels ranging from 2-114394 ng/L were used to measure hsTnI on Access 2 and DXI instruments. The between-method comparison of cTnI and hsTnI on DXI showed a slope of 1.003 with intercept of -43.31 and correlation coefficient (CC) of 0.9590. The mean bias was -5.1%, which was within the analytical imprecision range determined in our laboratory (2.2%-10.7%). However, comparison of cTnI and hsTnI in patients with troponin &amp;lt;20ng/L (n=103), the 99th percentile of the URL for males, showed the slope was 1.325 with intercept of -0.97 and CC of 0.7462. The mean bias was 1.91 (21.53%), which was much larger than the analytical imprecision. This is consistent with the fact that cTnI results are not reliable at the lower level due to the imprecision problem. Comparison of cTnI and hsTnI in patients with troponin &amp;gt;20ng/L (n=321) showed the slope was 1.006 with intercept of –60.09 and CC of 0.9576. The mean bias was -54.30 (-5.23%), which was within the analytical imprecision range. The within-method comparison of hsTnI on Access 2 and DXI 800 showed the slope was 1.138 with intercept of -633.0 and CC of 0.9888. The mean bias was 2126.4 (10.6%), within the analytical imprecision range. These data indicate that cTnI results above the 99th percentile URL are comparable with hsTnI results if both are tested on DXI 800, and hsTnI results tested on Access 2 and DXI 800 are comparable. Thus, to use the cardiac troponins assay properly, we suggest the laboratory report cardiac troponins with the assay and instrument names to reduce confusion during results comparison.

Performance evaluation of a novel high-sensitivity cardiac troponin T assay: analytical and clinical perspectives.

To evaluate the analytical characteristics of anovel high-sensitivity cardiac troponin T (hs-cTnT) test onthe automatic light-initiated chemiluminescent assay (LiCA®) system, and validated its diagnostic performance for non-ST-segment elevation myocardial infarction (NSTEMI). Studies included an extensive analytical evaluation and established the 99th percentile upper reference limit (URL) from apparently healthy individuals, followed by a diagnostic performance validation for NSTEMI. Sex-specific 99th percentile URLs were 16.0 ng/L (1.7 % CV: coefficient of variation) for men (21-92 years) and 13.4 ng/L (2.0 % CV) for women (23-87 years) in serum, and 30.6 ng/L (0.9 % CV) for men (18-87 years) and 20.2 ng/L (1.4 %CV) for women (18-88 years) in heparin plasma. Detection rates in healthy individuals ranged from 98.9 to 100 %. An excellent agreement was identified between LiCA® and Elecsys® assays with a correlation coefficient of 0.993 and mean bias of-0.7 % (-1.8-0.4 %) across the full measuring range, while the correlation coefficient and overall bias were 0.967 and-1.1 % (-2.5-0.3 %) for the lower levels of cTnT (10-100 ng/L), respectively. At the specific medical decision levels (14.0 and 52.0 ng/L), assay difference was estimated to be <5.0 %. No significant difference was found between these two assays in terms of area under curve (AUC), sensitivity and specificity, negative predictive value (NPV) and positive predictive value (PPV) for the diagnosis of NSTEMI. LiCA® hs-cTnT is a reliable 3rd-generation (level4) high-sensitivity assay for detecting cardiac troponin T. The assay is acceptable for practical use in the diagnosis of NSTEMI.

New insights on the mechanisms of myocardial injury in hypertensive patients with COVID-19

Abstract Introduction Cardiac comorbidities, particularly hypertension, are highly prevalent in patients hospitalized with COVID-19 and are related directly to the risk of clinical disease progression. Cardiac injury is the most frequently reported cardiac abnormality in these patients. Diverse forms and mechanisms of myocardial injury, including acute myocardial ischemia due to plaque rupture, oxygen supply/demand imbalance, non-ischemic injuries such as myocarditis, direct virus-mediated injury, and immune system dysregulation, have been described in patients with COVID-19. Purpose The mechanism of the association among hypertension, COVID-19 and cardiac injury and the reasons for worse clinical progression in these patients have not been elucidated clearly. Considering that myocardial injury due to direct SARS-CoV-2 infection is rare and that the immune system is often dysregulated in patients with COVID-19, and also that cytokine storm and lymphopenia are important immune markers of progression to severe disease, the present study aimed to investigate the immune profile of hypertensive patients with COVID-19 and myocardial injury to obtain a better understanding of the immune dysregulation and to provide new insights on the mechanism of myocardial injury in hypertensive patients with this disease. Methods All patients were selected prospectively from a multicenter registry of adults hospitalized with confirmed COVID-19. Cases had hypertension and myocardial injury, defined by troponin levels above the 99th percentile upper reference limit, and controls were hypertensive patients with no myocardial injury. Biomarkers and immune cell subsets were quantified and compared between the two groups. A multiple logistic regression model was used to analyze the associations of clinical and immune variables with myocardial injury. Results The sample comprised 193 patients divided into two groups: 47 cases and 146 controls. Relative to controls, cases had lower total lymphocyte count, percentage of T lymphocytes, CD8+CD38+ mean fluorescence intensity (MFI), and percentage of CD8+ human leukocyte antigen DR isotope (HLA-DR)+ CD38–cells and higher percentage of natural killer lymphocytes, natural killer group 2A (NKG2A)+ MFI, percentage of CD8+CD38+cells, CD8+HLA-DR+MFI, CD8+NKG2A+MFI, and percentage of CD8+HLA-DR–CD38+cells. On multivariate regression, the CD8+HLA-DR+MFI, CD8+CD38+MFI, and total lymphocyte count were associated significantly with myocardial injury. Conclusion Our findings suggest that lymphopenia, CD8+CD38+MFI, and CD8+HLA-DR+MFI are immune biomarkers of myocardial injury in hypertensive patients with COVID-19. The immune signature described here may aid in understanding the mechanisms underlying myocardial injury in these patients. The study data might open a new window for improvement in the treatment of hypertensive patients with COVID-19 and myocardial injury.

High-sensitivity cardiac troponin-T concentrations and their prognostic implications in paroxysmal supraventricular tachycardia: A nationwide study

Abstract Introduction Paroxysmal supraventricular tachycardia (PSVT) may mimic symptoms and electrocardiographic findings compatible with acute coronary syndromes. As a result, cardiac troponin concentrations are frequently measured upon presentation. Although PSVT may increase troponin concentrations, the expected magnitude and prognostic clinical value of high-sensitivity troponin (hs-TnT) concentrations remain uncertain. Purpose The purpose of this study was to examine whether elevated hs-TnT concentrations in PSVT patients were associated with a higher risk of death from any cause. Methods We used Danish nationwide registry data from January 2013 through December 2019. PSVT was defined as all supraventricular tachycardias except atrial fibrillation and atrial flutter. The inclusion criteria were de novo PSVT and at least one measured hs-TnT level during hospitalization. Exclusion criteria were a history of cardiovascular disease (coronary artery disease, atrial fibrillation or flutter, or heart failure) or absence of hemoglobin or creatinine measurement within one day of the hs-TnT measurement. Elevated hs-TnT was defined as a value of ≥14 ng/l (the conventional 99th percentile upper reference limit). The primary outcome was death from any cause evaluated at 0-30 and 31-365 days, using multivariable Cox regression with average treatment effect, rendering standardized absolute and relative risks. Results A total of 1029 patients were included. Median age was 58 years (25th to 75th percentile: 45-71), and 45% were male. Elevated hs-TnT level was observed in 674 (65.5%) patients, who also had a higher prevalence of cardiovascular comorbidities. The median hs-TnT level was 16 ng/l (25th to 75th percentile: 10-35). The standardized mortality risk at 30 days was significantly higher in patients with elevated hs-TnT compared with patients with normal hs-TnT concentrations (2.38% [95% confidence interval (CI): 1.38 to 3.37] versus &amp;lt;0.01% [95% CI: &amp;lt;0.01 to &amp;lt;0.01]) (Figure 1). The relative risk was 58722906 (95% CI: 23126570 to 94319242), p = 0.001. At 31-365 days, the standardized risk of death was 1.51% (95% CI: 0 to 3.28) in individuals with a normal hs-TnT and 4.23% (95% CI: 2.81 to 5.66) in those with an elevated hs-TnT (Figure 2), resulting in a relative risk of 2.81 (95% CI: 0 to 6.32), p = 0.31. Conclusion In patients without prior cardiovascular disease, an elevated hs-TnT concentration during the first episode of PSVT was only associated with an increased early mortality risk. Long-term mortality was not affected by elevated hs-TnT.Figure 1Figure 2

Prognostic significance of chronic myocardial injury diagnosed by three different cardiac troponin assays in patients admitted with suspected acute coronary syndrome.

Chronic myocardial injury (CMI) is defined as stable concentrations of cardiac troponin T or I (cTnT or cTnI) above the assay-specific 99th percentile upper reference limit (URL) and signals poor outcome. The clinical implications of diagnosing CMI are unclear. We aimed to assess prevalence and association of CMI with long-term prognosis using three different high-sensitivity cTn (hs-cTn) assays. A total of 1,292 hospitalized patients without acute myocardial injury had cTn concentrations quantified by hs-cTn assays by Roche Diagnostics, Abbott Diagnostics and Siemens Healthineers. The median follow-up time was 4.1 years. The prevalence of CMI and hazard ratios for mortality and cardiovascular (CV) events were calculated based on the URL provided by the manufacturers and compared to the prognostic accuracy when lower percentiles of cTn (97.5, 95 or 90), limit of detection or the estimated bioequivalent concentrations between assays were used as cutoff values. There was no major difference in prognostic accuracy between cTnT and cTnI analyzed as continuous variables. The correlation between cTnT and cTnI was high (r=0.724-0.785), but the cTnT assay diagnosed 3.9-4.5 times more patients with having CMI based on the sex-specific URLs (TnT, n=207; TnI Abbott, n=46, TnI Siemens, n=53) and had higher clinical sensitivity and AUC at the URL. The prevalence of CMI is highly assay-dependent. cTnT and cTnI have similar prognostic accuracy for mortality or CV events when measured as continuous variables. However, a CMI diagnosis according to cTnT has higher prognostic accuracy compared to a CMI diagnosis according to cTnI.

Assessment of Pulmonary Arteries Hemodynamics and Its Relationship With Cardiac Remodeling and Myocardial Fibrosis in Athletes With Four-Dimensional Flow MRI.

Exercise-induced cardiac remodeling (CR) and myocardial fibrosis (MF) can increase cardiovascular risk in athletes. Early detection of pulmonary arterial hemodynamics parameters among athletes may be beneficial in optimizing the frequency of clinical follow-ups. To analyze the hemodynamics of pulmonary arteries and its relationship with CR and MF in athletes using four-dimensional (4D) flow MRI. Prospective. One hundred twenty-one athletes (median age, 24 years; mean exercise per week 10 hours, for mean of 5 years) and twenty-onesedentary healthy controls (median age, 25 years; exercise per week <3 hours, irregular pattern). True fast imaging with steady state free precession, time-resolved 3D Cartesian phase-contrast, and phase sensitive inversion recovery late gadolinium enhancement sequences at 3.0 T. CR was defined as any cardiac parameters exceeding the 99th percentile upper reference limits, encompassing ventricular function, bi-atrium and bi-ventricle diameters, and ventricular wall thickness. MF was visually evaluated by three independent radiologists. 4D flow parameters were assessed in the main, right, and left pulmonary arteries (MPA, RPA, and LPA, respectively) and compared between different groups. Four machine learning (ML) models were developed to differentiate between athletes with and without CR and/or MF. Univariate analysis was used to compare groups. Area under the receiver operating characteristic curve (AUC) was used to assess the performance of the ML models. Athletes had significantly higher WSSmax in the MPA, RPA, and LPA than controls. Athletes with CR and/or MF (N = 30) had significantly lower RPmax from MPA to RPA than those without (N = 91). Among the ML models, the gradient boosting machine model had the highest performance, with an AUC of 0.90. The pulmonary arterial hemodynamics parameters could differentiate CR and/or MF in athletes, which may be potential to assist in optimizing frequency of follow-up. 1 TECHNICAL EFFICACY: Stage 2.

A-011 High Sensitive Troponin Assays for Differentiating the Patients with Unstable Angina from Stable Angina

Abstract Background There have been no cardiac biomarkers used in the diagnosis of unstable angina. In this study, we examined high sensitive troponin T and I as a marker to differentiate the patients with unstable angina from the patients with stable angina. Methods A total of 816 patients (59 AMI, 94 unstable angina, 99 stable angina, 623 healthy individuals) were included. All patients had glomerular filtration rate of ≥60 mL/min/1.73 m2. Leftover serum samples were obtained from the patients who visited The Catholic University of Korea, St Vincent’s Hospital from April to November, 2019. Cardiac troponin was measured using Beckman Coulter Access high sensitivity cTnI assay, Abbott Architect high sensitive TnI assay, and Roche Elecsys Troponin T-high sensitive assay. Results The 99th percentile URLs (Upper Reference Limits) of Beckman Coulter cTnI, Abbott cTnI, and Roche cTnT are 9.8 ng/L, 17.9 ng/L, and 16.4 ng/L, respectively. In the 99 patients with stable angina, 9.1% (9/99), 5.1% (5/99), and 6.1% (6/99) of the patients showed higher values than each the 99th percentile URL with Beckman Coulter cTnI, Abbott cTnI, and Roche cTnT, respectively. In the 94 patients with unstable angina, 24.5% (23/94), 24.5% (23/94), and 25.5% (24/94) showed higher values than each the 99th percentile URL with Beckman Coulter cTnI, Abbott cTnI, and Roche cTnT, respectively. There are significant differences between the frequencies of the patients with stable angina and unstable angina showing higher values of cardiac troponins than each the 99th percentile URL. Conclusion High sensitive troponins could be a useful marker for the differentiation of the patients with unstable angina from stable angina.

A-009 Analytical Concordance of High-Sensitivity Cardiac Troponin I and T Assays in Patients From the CONTRAST Trial Presenting to an Emergency Department

Abstract Background There are limited data on the analytical concordance of high-sensitivity cardiac troponin (hs-cTn) T and hs-cTnI assays. The goal of this study was to evaluate the concordance of one hs-cTnT and one hs-cTnI assay relative to each assay’s limit of quantitation (LoQ) and 99th percentile upper reference limit (URL). Methods The Comparison of Troponin I and T Assays Trial (CONTRAST) NCT03214029 is an observational study that evaluated the concordance of two FDA-cleared hs-cTn assay concentrations measured at presentation (0 h) and 2 h by the Abbott ARCHITETCT i2000 hs-cTnI (clinically used assay) and Roche cobas 601 Gen 5 hs-cTnT (measured for investigational purposes) from consecutively enrolled patients presenting to an urban US medical center with symptoms suggestive of ischemia. Concordance at presentation (0 h) was assessed relative to each assay’s FDA-cleared reporting concentration (LoQ), and FDA-cleared sex-specific 99th percentile URLs. The incidence of myocardial injury, defined as at least one concentration above the 99th percentile URL over serial sampling, was also evaluated. Results At presentation hs-cTn concentrations &amp;lt;LoQs (Abbott 3.5 ng/L, Roche 6 ng/L) were 834/2270 (37%) and 530/2270 (23%), respectively. The concordance of results &amp;lt;LoQ was 81%. The Abbott assay showed a higher percent of concentrations below both female and male URLs than did the Roche assay. For females, concentrations below the sex-specific 99th percentile URLs were 707/945 (75%) for Abbott hs-cTnI (16 ng/L) and 545/945 (58%) for Roche hs-cTnT (14 ng/L, P &amp;lt; 0.03). For males, concentrations below the sex-specific 99th percentile URLs were 1100/1325 (83%) for Abbott hs-cTnI (34 ng/L) and 900/1325 (68%) for Roche hs-cTnT (22 ng/L). The concordance of results below the sex-specific 99th percentile URLs for both assays was 80%. Among males with presentation concentrations &amp;lt;URL, the incidence of myocardial injury (hs-cTn &amp;gt;URL at 2 h) was approximately two-fold greater for the Roche hs-cTnT (59/900, 6.2%) than Abbott hs-cTnI (31/1110, 2.8%). Females with presentation concentrations &amp;lt;URL showed similar rates of myocardial injury at 2 h for the Roche (24/545 [4.4%]) and Abbott assays (36/707 [5.1%]). Conclusion We report a 20% discordance between Abbott hs-cTnI and Roche hs-cTnT assays in detecting myocardial injury at respective 99th percentile URLs and at each assays’ FDA allowed LoQ reporting limit.