99th Percentile Upper Reference Limit Research Articles

Prognostic importance of persistent elevations in high-sensitivity troponin T in the early convalescent phase (two weeks) following high-risk myocardial infarction: insights from the PARADISE-MI trial

Abstract Introduction Myocardial infarction (MI) is defined by a rise and fall in cardiac troponin (cTn) with clinical evidence of acute myocardial ischemia. How often cTn remains elevated in high-risk patients stabilized following MI and the relation between convalescent cTn levels and subsequent clinical outcomes in these patients is unknown. Aims To evaluate the prognostic importance of high-sensitivity cTn T (hs-cTnT) in the early convalescent phase of a MI for a range of cardiovascular (CV) outcomes in patients enrolled in the Prospective ARNI vs ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI). Methods Patients ≥18 years without prior heart failure (HF) (n=5661) were randomized to sacubitril/valsartan or ramipril within 0.5 to 7 days of MI complicated by transient pulmonary congestion, LVEF ≤40%, or both. Hs-cTnT was measured using the Roche Elecsys Troponin T-high-sensitive assay in 1093 patients two weeks after randomization (median 2.6 weeks after the index MI). Associations between log (2)-transformed hs-cTnT and clinical outcomes were investigated in landmark analyses using Cox regression models adjusted for clinical covariates of known prognostic importance and NT-proBNP (Figure). Results Median week 2 hs-cTnT concentration was 34 ng/L [IQR 17-94 ng/L] and exceeded the 99th percentile upper reference limit in 69% of patients. Patients with persistently elevated hs-cTnT concentrations (n=753) were older, more likely men, more commonly had atrial fibrillation and lower estimated glomerular filtration rate and less likely had a prior MI. They more commonly had presented with ST-segment elevation MI and pulmonary congestion and had higher concentrations of NT-proBNP. Rates of primary reperfusion were similar. Log(2)-transformed hs-cTnT was only weakly correlated with LVEF (rho = -0.15, p<0.001), irrespective of the type of MI. hs-cTnT was independently and linearly associated with the primary composite outcome of CV death or incident HF (adj HR 1.17 per doubling; 95% CI, 1.03 – 1.34), all-cause death (adj HR 1.20; 95% CI, 1.01 – 1.44) and CV death (adj HR 1.25; 95% CI, 1.02 – 1.52) but not with non-CV death (adj HR 1.04; 95% CI, 0.70-1.54). hs-cTnT was not significantly associated with recurrent fatal or non-fatal MI (adj HR 1.00; 95% CI, 0.85-1.18) (Figure). Concentrations of week 2 hs-cTnT were not altered by sacubitril/valsartan relative to ramipril (+4%; 95% CI, -8% to 18%). Conclusions Persistent elevations in hs-cTnT during the early convalescent phase following high-risk MI are common and are associated with heightened risk of all-cause death, CV death and incident HF but not of recurrent MI or non-CV death. hs-cTnT measured ~2.5 weeks after high-risk MI provides incremental prognostic information beyond traditional risk factors and NT-proBNP.

Rapid Ventricular Pacing for Clipping of Intracranial Aneurysms: A Single-centre Retrospective Case Series.

Multiple strategies exist to facilitate microdissection and obliteration of intracranial aneurysms during microsurgical clipping. Rapid ventricular pacing (RVP) can be used to induce controlled transient hypotension to facilitate aneurysm manipulation. We report the indications and outcomes of intraoperative RVP for clipping of ruptured and unruptured complex aneurysms. We completed a retrospective review of adult patients who underwent RVP-facilitated elective and emergent microsurgical aneurysm clipping by a single senior neurosurgeon between 2016 and 2023. Intraoperative RVP was performed at a rate of 150 to 200 beats per minute through a transvenous pacing wire and repeated as needed based on surgical requirements. Intraoperative procedural and pacing data and perioperative cardiac and neurosurgical variables were collected. Forty patients were included in this study. The median (interquartile range) number of pacing episodes per patient was 8 (5 to 14), resulting in a median mean arterial pressure of 37 (30 to 40) mm Hg during RVP. One patient developed wide complex tachycardia intraoperatively, which resolved after cardioversion. Fifteen out of 36 (42%) patients who had postoperative troponin measurements had at least one troponin value above the 99th percentile upper reference limit. One patient had markedly elevated troponin with anterolateral ischemia in the context of massive postoperative intracranial hemorrhage. There were no other documented intraoperative or postoperative cardiac events. This retrospective case series suggests that RVP could be an effective adjunct for clipping of complex ruptured and unruptured aneurysms, associated with transient troponin rise but rare postoperative cardiac complications.

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.

Incidence, Predisposing Factors, and Outcomes of Periprocedural Myocardial Infarction in Elective Patients Undergoing Coronary Intervention

Objectives: This study aims to investigate the incidence, clinical characteristics, and outcomes associated with periprocedural myocardial infarction (PMI) following elective percutaneous coronary intervention (PCI). Methodology: A retrospective analysis was conducted on 120 patients who underwent elective PCI between January 2023 and December 2023. Data encompassed patient demographics, procedural specifics, and post-procedural outcomes, including PMI occurrence defined by elevated cardiac troponin levels exceeding the 99th percentile upper reference limit. Statistical analyses included logistic regression to evaluate the association of various predictors with PMI incidence. Results: The PMI incidence in our cohort stood at 2.5%. Significant predictors of PMI encompassed older age, male gender, higher lesion complexity, and the utilization of bare-metal stents. Patients experiencing PMI exhibited a substantially higher rate of subsequent major adverse cardiovascular events (MACE) within six months post-procedure (33% vs. 4.27%, p = 0.045). Conclusion: PMI persists as a notable complication of elective PCI, intricately linked to adverse long-term cardiovascular outcomes. These findings underscore the imperative for meticulous patient and procedural selection to mitigate PMI risk. Given PMI's substantial implications for patient prognosis, future research should concentrate on refining risk assessment tools and crafting targeted interventions to reduce PMI incidence and enhance overall patient outcomes.

Cardiac troponin concentrations following exercise and the association with cardiovascular disease and outcomes: rationale and design of the prospective TREAT cohort study

Exercise can produce transient elevations of cardiac troponin (cTn) concentrations, which may resemble the cTn release profile of myocardial infarction. Consequently, clinical interpretation of postexercise cTn elevations (ie, values above...

Plasma levels of bactericidal/permeability-increasing protein correlate with systemic inflammation in acute coronary syndrome

BackgroundNeutrophils play important roles in atherosclerosis and atherothrombosis. Bactericidal/permeability-increasing protein (BPI) is mainly expressed in the granules of human neutrophils in response to inflammatory stress. This observational, cross-sectional study investigated the plasma level of BPI in patients with acute coronary syndrome (ACS) and its correlation with blood neutrophil counts and circulating inflammatory biomarkers. MethodsA total of 367 patients who had acute chest pain and who were admitted to our hospital for coronary angiography (CAG) and/or percutaneous coronary intervention (PCI) from May 1, 2020 to August 31, 2020 were recruited. Among them, 256 had a cardiac troponin value above the 99th percentile upper reference limit and were diagnosed with ACS. The remaining patients (n = 111) were classified as non-ACS. The TIMI and GRACE scores were calculated at admission. The Gensini score based on CAG was used to determine atherosclerotic burden. Plasma levels of interleukin (IL)-1β, myeloperoxidase-DNA (MPO-DNA), high sensitivity C-reactive protein (hs-CRP), S100A8/A9, and BPI were measured using enzyme-linked immunosorbent assays. Correlations of plasma BPI levels with examination scores and levels of circulating inflammatory biomarkers were explored. Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic efficacy of BPI for ACS and myocardial infarction. ResultsPatients in the ACS group showed significantly higher plasma BPI levels compared to the non-ACS group (46.42 ± 16.61 vs. 16.23 ± 6.19 ng/mL, p < 0.05). Plasma levels of IL-1β, MPO-DNA, hs-CRP, and S100A8/A9 in the ACS group were also significantly higher than those in the non-ACS group (all p < 0.05). In addition, plasma BPI levels were positively correlated with the TIMI, GRACE, and Gensini scores (r = 0.176, p = 0.003; r = 0.320, p < 0.001; r = 0.263, p < 0.001, respectively) in patients with ACS. Plasma BPI levels were also positively correlated with blood neutrophil counts (r = 0.266, p < 0.001) and levels of circulating inflammatory biomarkers (IL-1β, r = 0.512; MPO-DNA, r = 0.452; hs-CRP, r = 0.554; S100A8/A9, r = 0.434; all p < 0.001) in patients with ACS. ROC curve analysis revealed that the diagnostic efficacy of BPI for ACS was not inferior to that of IL-1β, MPO-DNA, hs-CRP, S100A8/A9, or blood neutrophil counts. ROC analysis also showed that the diagnostic efficacy of BPI for myocardial infarction was not inferior to that of creatine kinase (CK)-MB or cardiac troponin I. ConclusionBPI is associated with systemic inflammation in ACS and may be involved in the process of atherosclerosis and atherothrombosis. The potential of BPI as a prognostic and diagnostic biomarker for ACS should be investigated in clinical settings.

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.

Elevated Cardiac Troponin I as a Mortality Predictor in Hospitalised COVID-19 Patients.

Background and Objectives: SARS-CoV-2 affects multiple organ systems, including the cardiovascular system, leading to immediate and long-term cardiovascular complications. Acute myocardial injury is one of the earliest and most common cardiac issues in the acute phase of COVID-19. This study aimed to evaluate the prognostic value of cardiac troponin I (cTnI) levels in predicting in-hospital mortality among hospitalised COVID-19 patients. Materials and Methods: A retrospective observational cohort study included 2019 adult patients hospitalised with a confirmed COVID-19 infection stratified by cTnI levels on admission into three groups: <19 ng/L (1416 patients), 19-100 ng/L (431 patients), and >100 ng/L (172 patients). Myocardial injury was defined as blood serum cTnI levels increased above the 99th percentile upper reference limit. Depersonalised datasets were extracted from digital health records. Statistical analysis included multivariable binary logistic and Cox proportional hazards regressions. Results: Overall, 29.87% of patients experienced acute myocardial injury, which development was associated with age, male sex, chronic heart failure, arterial hypertension, obesity, and chronic kidney disease. Among patients with cTnI levels of 19-100 ng/L, the odds ratio for requiring invasive mechanical ventilation was 3.18 (95% CI 2.11-4.79) and, for those with cTnI > 100 ng/L, 5.38 (95% CI 3.26-8.88). The hazard ratio for in-hospital mortality for patients with cTnI levels of 19-100 ng/L was 2.58 (95% CI 1.83-3.62) and, for those with cTnI > 100 ng/L, 2.97 (95% CI 2.01-4.39) compared to patients with normal cTnI levels. Conclusions: Increased cardiac troponin I, indicating myocardial injury, on admission is associated with a more adverse clinical disease course, including a higher likelihood of requiring invasive mechanical ventilation and increased risk of in-hospital mortality. This indicates cardiac troponin I to be a beneficial biomarker for clinicians trying to identify high-risk COVID-19 patients, choosing the optimal monitoring and treatment strategy for these patients.

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.

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.

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.

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.

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.

Determination of sex and age specific 99th percentile upper reference limit of high sensitivity cardiac Troponin I in a sample of apparently healthy Iraqi adults

Determination of sex and age specific 99th percentile upper reference limit of high sensitivity cardiac Troponin I in a sample of apparently healthy Iraqi adults

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.