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Background: There are limited data regarding the utility of follow-up cardiac troponin (cTn) measurements after admission for acute chest pain and how long-term stability of myocardial injury and prognostic value differ when using cardiac troponin T (cTnT) or I (cTnI)., Methods: We measured high-sensitivity (hs)-cTnT (Roche Diagnostics) and hs-cTnI (Siemens Healthineers) during hospitalization for acute chest pain and after 3 months. Acute myocardial injury was defined as concentrations > sex-specific upper reference limit (URL) during hospitalization and ≤URL at 3-months. Chronic myocardial injury (CMI) was defined as concentrations > URL at both time points. Patients were followed from the 3-month sampling point for a median of 1586 (IQR 1161-1786) days for a primary composite endpoint of all-cause mortality, myocardial infarction (MI), revascularization, and heart failure, and a secondary endpoint of all-cause mortality., Results: Among 754 patients, 33.8% (hs-cTnT) and 19.2% (hs-cTnI) had myocardial injury during hospitalization. The rate of CMI was 5 times higher by hs-cTnT (20%) assay than hs-cTnI (4%), while acute myocardial injury was equally common; 14% (hs-cTnT) and 15% (hs-cTnI), respectively (6% and 5% when excluding index non-ST-elevation MI (NSTEMI). For hs-cTnT, peak index concentration, 3-month concentration and classification of CMI predicted the primary endpoint; hazard ratios (HRs) 1.38 (95% CI 1.20-1.58), 2.34 (1.70-3.20), and 2.31 (1.30-4.12), respectively. For hs-cTnI, peak index concentration predicted the primary endpoint; HR 1.14 (1.03-1.25). This association was nonsignificant after excluding index NSTEMI., Conclusions: Acute myocardial injury is equally frequent, whereas CMI is more prevalent using hs-cTnT assay than hs-cTnI. Measuring hs-cTnT 3 months after an acute chest pain episode could assist in further long-term risk assessment. ClinicalTrials.gov Registration Number: NCT02620202., (© Association for Diagnostics & Laboratory Medicine 2024.)

Background: 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., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2024 International Anesthesia Research Society.)

Background: Measurement of cardiac troponin (cTn) by a high sensitivity method is now the recommended strategy for the detection of myocardial injury. An international survey was undertaken to assess how this has been implemented., Methods: A questionnaire based around 14 domains on cardiac biomarkers was distributed electronically with the aid of professional societies accessed by a web link within the invitation. Results were returned electronically then extracted into a relational database for analysis., Results: Responses were obtained from 663 laboratories across 76 countries ranging from 1 to 69 largest country. The majority of responses (79.6%) came from the European area. Responses were grouped into broad geographic areas for analysis. Most responses came from hospitals providing a local and regional service of which the majority provided angioplasty. cTn measurement was the dominant biomarker. The majority of laboratories include creatine kinase (CK) in their cardiac profile and approximately 50% also offer the MB isoenzyme of CK. The majority of laboratories (91.9%) measure cTn by a high sensitivity method. Sex specific reference ranges were typically implemented for cardiac troponin I but not for cardiac troponin T. The preferred unit of measurement was nanograms/L. A structured decision-making pathway utilising high sensitivity cTn measurement was used by 83.3% of laboratories who responded. Single sample rule out is common but the majority used serial sampling strategy based on measurement on admission and three hours., Conclusions: Measurement of cTn by a high sensitivity method is now well established internationally, the use of rapid diagnostic protocols lags behind., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [POC: Honoria Siemens Healthineers, Abbott Laboratories; Advisory Boards Radiometer, Psyros diagnostics, LumiraRx, Siemens Healthineers; Consultant to IFCC Committee on Clinical Applications of Cardiac Bio-Markers (C-CB). AHL: Honoraria Siemens Healthineers, Abbott Laboratories; Research support from Abbott Laboratories, Beckman Coulter and Siemens Healthineers. KA: Research Grants Siemens Healthineers, Roche Diagnostics; Consultancy CardiNor; Honoraria Siemens Healthineers, SNIBE; Advisory Boards Roche Diagnostics, Siemens Healthineers, SpinChip; Associate Editor Clinical Biochemistry, Chair International Federation of Clinical Chemistry Committee on Clinical Application of Cardiac Bio-Markers. DG: None. JS: None. KP: None. SS: Honoria Roche Diagnostics, Abbott Laboratories, SNIBE; President Serbian Society for Clinical Laboratory and Science (SCLM). HB: Grants Roche Diagnostics, Beckman Coulter. MTHL Clinical Research Training Fellowships (MR/W000598/1) from the Medical Research Council. NLM Chair Award (CH/F/21/90010), Programme Grant (RG/20/10/34966) and a Research Excellence Award (RE/18/5/34216) from the British Heart Foundation; Honoraria Abbott Laboratories, Siemens Healthineers, Roche Diagnostics; Advisory Boards Psyros Diagnostics, Roche Diagnostics, LumiraDx; Research Support Siemens Healthineers. PL. Chair Science Committee LabQuality Days.]., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The relationship between exercise-induced troponin elevation and non-obstructive coronary artery disease (CAD) is unclear. This observational study assessed non-obstructive CAD's impact on exercise-induced cardiac Troponin I (cTnI) elevation in middle-aged recreational athletes. cTnI levels of 40 well-trained recreational athletes (73% males, 50 ± 9 years old) were assessed by a high-sensitive cTnI assay 24 h before, and at 3 and 24 h following two high-intensity exercises of different durations; a cardiopulmonary exercise test (CPET), and a 91-km mountain bike race. Workload was measured with power meters. Coronary computed tomography angiography was used to determine the presence or absence of non-obstructive (<50% obstruction) CAD. A total of 15 individuals had non-obstructive CAD (Atherosclerotic group), whereas 25 had no atherosclerosis (normal). There were higher post-exercise cTnI levels following the race compared with CPET, both at 3 h (77.0 (35.3-112.4) ng/L vs. 11.6 (6.4-22.5) ng/L, p < 0.001) and at 24 h (14.7 (6.7-16.3) vs. 5.0 (2.6-8.9) ng/L, p < 0.001). Absolute cTnI values did not differ among groups. Still, the association of cTnI response to power output was significantly stronger in the CAD versus Normal group both at 3 h post-exercise (Rho = 0.80, p < 0.001 vs. Rho = -0.20, p = 0.33) and 24-h post-exercise (Rho = 0.87, p < 0.001 vs. Rho = -0.13, p = 0.55). Exercise-induced cTnI elevation was strongly correlated with exercise workload in middle-aged athletes with non-obstructive CAD but not in individuals without CAD. This finding suggests that CAD influences the relationship between exercise workload and the cTnI response even without coronary artery obstruction., (© 2024 The Author(s). Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.)

Objectives: Secretoneurin (SN) is a novel cardiac biomarker that associates with the risk of mortality and dysfunctional cardiomyocyte Ca 2+ handling in heart failure patients. Reference intervals for SN are unknown., Methods: SN was measured with a CE-marked ELISA in healthy community dwellers from the fourth wave of the Trøndelag Health Study (HUNT4) conducted in 2017-2019. The common, sex and age specific 90th, 95th, 97.5th and 99th percentiles were calculated using the non-parametric method and outlier exclusion according to the Reed test. The applicability of sex and age specific reference intervals were investigated using Harris and Boyd test. We also estimated the percentiles in a subset with normal findings on echocardiographic screening., Results: The total cohort included 887 persons (56.4 % women). After echocardiographic screening 122 persons were excluded, leaving a total of 765 persons (57.8 % women). The 97.5th percentile (95 % CI in brackets) of SN was 59.7 (57.5-62.1) pmol/L in the total population and 58.6 (57.1-62.1) pmol/L after echocardiography screening. In general, slightly higher percentiles were found in women and elderly participants, but less than 4 % in these subgroups had concentrations deviating from the common 97.5th percentile. Low BMI or eGFR was also associated with higher concentrations of SN., Conclusions: Upper reference limits for SN were similar amongst healthy adult community dwellers regardless of prescreening including cardiac echocardiography or not. Women and elderly showed higher concentrations of SN, but the differences were not sufficiently large to justify age and sex stratified upper reference limits., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Objective: Growth differentiation factor-15 (GDF-15) is a predictor of death and cardiovascular events when measured during index hospitalisation in patients with acute chest pain. This study investigated the prognostic utility of measuring GDF-15 3 months after an admission with suspected non-ST-elevation acute coronary syndrome (NSTE-ACS)., Methods: GDF-15 was measured at baseline and 3 months after admission in 758 patients admitted with suspected NSTE-ACS. Patients were followed for a median of 1540 (IQR: 1087-1776) days after the 3-month visit. The primary endpoint was all-cause mortality, while the secondary composite endpoint included all-cause mortality, incident myocardial infarction and heart failure hospitalisation during follow-up., Results: In patients with GDF-15 ≥1200 pg/mL (n=248), 18% died and 25% met the composite endpoint. In patients with GDF-15 <1200 pg/mL (n=510), 1.7% died and 4% met the composite endpoint. The GDF-15 concentration (log2 transformed) at 3 months was significantly associated with all-cause mortality (adjusted HR: 2.2, 95% CI: 1.4 to 3.3, p<0.001) and the composite endpoint (adjusted HR: 1.9, 95% CI: 1.4 to 2.7, p<0.001), independently of traditional risk factors and baseline troponin T. A 10% change in GDF-15 concentration from baseline to the 3-month visit was associated with increased risk of all-cause mortality (HR: 1.06, 95% CI: 1.01 to 1.13, p=0.031), adjusting for baseline GDF-15 concentrations., Conclusions: High GDF-15 concentrations 3 months after admission for suspected NSTE-ACS are associated with long-term mortality and cardiovascular events, independent of traditional risk factors and troponin T. A change in GDF-15 concentration can provide prognostic information., Competing Interests: Competing interests: KMA has served on advisory board for Roche Diagnostics and SpinChip, consultant honoraria from CardiNor, lecturing honorarium from Siemens Healthineers and Snibe Diagnostics, and research grants from Siemens Healthineers and Roche Diagnostics. She is the Associate Editor of Clinical Biochemistry and Chair of the IFCC Committee of Clinical Application of Cardiac Bio-markers. TO has received speaker and/or consultancy honoraria from Abbott Diagnostics, Bayer, CardiNor, Roche Diagnostics and Siemens Healthineers, and has received research support from Abbott Diagnostics, Novartis, Roche Diagnostics, via Akershus University Hospital. ØS has received lecture fees from Abbott Diagnostics. GMSM, O-TS, HLT, JL, ROB, VVSB, ØRM and KV have no disclosures., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cardiac troponin measurements are indispensable for the diagnosis of myocardial infarction and provide useful information for long-term risk prediction of cardiovascular disease. Accelerated diagnostic pathways prevent unnecessary hospital admission, but require reporting cardiac troponin concentrations at low concentrations that are sometimes below the limit of quantification. Whether analytical imprecision at these concentrations contributes to misclassification of patients is debated., Content: The International Federation of Clinical Chemistry Committee on Clinical Application of Cardiac Bio-Markers (IFCC C-CB) provides evidence-based educational statements on analytical and clinical aspects of cardiac biomarkers. This mini-review discusses how the reporting of low concentrations of cardiac troponins impacts on whether or not assays are classified as high-sensitivity and how analytical performance at low concentrations influences the utility of troponins in accelerated diagnostic pathways. Practical suggestions are made for laboratories regarding analytical quality assessment of cardiac troponin results at low cutoffs, with a particular focus on accelerated diagnostic pathways. The review also discusses how future use of cardiac troponins for long-term prediction or management of cardiovascular disease may require improvements in analytical quality., Summary: Clinical guidelines recommend using cardiac troponin concentrations as low as the limit of detection of the assay to guide patient care. Laboratories, manufacturers, researchers, and external quality assessment providers should extend analytical performance monitoring of cardiac troponin assays to include the concentration ranges applicable in these pathways., (© Association for Diagnostics & Laboratory Medicine 2023.)

Background: An 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., Methods: Human 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., Results: The CVs for all individual instruments and overall were ≤ 10.0 % for two manufacturers (Abbott CV pooled  = 6.3 % and Beckman CV pooled  = 7.0 %). One of four Siemens Atellica instruments yielded a CV > 10.0 % (CV pooled  = 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) (CV pooled  = 11.7 %). Four Roche instruments also yielded CVs > 10.0 % near the female URL of 14 ng/L used in the United States (CV pooled  = 8.5 %)., Conclusions: The 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no other/known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Severe obesity is associated with increased risk of non-alcoholic fatty liver disease and cardiovascular disease. We hypothesized that liver fibrosis as quantified by the Enhanced Liver Fibrosis (ELF) test would be predictive of myocardial injury and fibrosis, expressed by higher concentrations of cardiac troponin T and I measured by high-sensitivity assays (hs-cTnT and hs-cTnI, respectively)., Material and Methods: We performed cross-sectional analyses of baseline data from 136 patients (mean age 45 years, 38 % male) with severe obesity participating in the non-randomized clinical trial Prevention of Coronary Heart Disease in Morbidly Obese Patients (ClinicalTrials.gov NCT00626964). Associations between ELF scores, hs-cTnT, and hs-cTnI concentrations were assessed using linear regression analysis., Results: ELF scores were associated with hs-cTnT in the unadjusted model (B 0.381, 95 % Confidence Interval [CI] 0.247, 0.514), but the association was attenuated upon adjustment for potential confounders (B -0.031, 95 % CI -0.155, 0.093). Similarly, for hs-cTnI, an observed association with ELF scores in the unadjusted model was attenuated upon adjustment for potential confounders ((B 0.432, 95 % CI 0.179, 0.685) and (B 0.069, 95 % CI -0.230, 0.367), respectively). Age, sex, hypertension, and estimated glomerular filtration rate were amongst the shared predictors of ELF score, hs-cTnT, and hs-cTnI that provided the univariable models with the highest R-squared and lowest Akaike Information Criterion values., Conclusions: Contrary to our hypothesis, ELF score did not predict myocardial injury and fibrosis, but we rather demonstrated an association between liver fibrosis and myocardial injury and fibrosis may be explained by shared risk factors of cardiovascular disease., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: T.O. has received honoraria from Roche Diagnostics, Abbott Laboratories, Bayer and CardiNor not related to the current work, and nonfinancial support from Novartis, ChromaDexSomaLogic, Abbott Diagnostics, and Roche Diagnostics via institution. K.M.A. is an Associate Editor of Clinical Biochemistry and Chair of the International Federation of Clinical Chemistry Committee on Clinical Application of Cardiac Bio-Markers, she has served on advisory boards for Roche Diagnostics, Siemens Healthineers and SpinChip, and has received honorarium for consultancy from CardiNor, honorarium for lecturing from Siemens Healthineers and Snibe Diagnostics, and research grants from Siemens Healthineers and Roche Diagnostics. The remaining authors have no conflicts of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Patients presenting with symptoms suggestive of acute coronary syndrome (ACS) contribute to a high workload and overcrowding in the Emergency Department (ED). Accelerated diagnostic protocols for non-ST-elevation myocardial infarction have proved challenging to implement. One obstacle is the turnaround time for analyzing high-sensitivity cardiac troponin (hs-cTn). In the WESTCOR-POC study (Clinical Trials number NCT05354804) we aim to evaluate safety and efficiency of a 0/1 h hs-cTn algorithm utilizing a hs-cTnI point of care (POC) instrument in comparison to central laboratory hs-cTnT measurements., Design: This is a prospective single-center randomized clinical trial aiming to include 1500 patients admitted to the ED with symptoms suggestive of ACS. Patients will receive standard investigations following the European Society of Cardiology 0/1h protocols for centralized hs-cTnT measurements or the intervention using a 0/1h POC hs-cTnI algorithm. Primary end-points are 1) Safety; death, myocardial infarction or acute revascularization within 30 days 2) Efficiency; length of stay in the ED, 3) Cost- effectiveness; total episode cost, 4) Patient satisfaction, 5) Patient symptom burden and 6) Patients quality of life. Secondary outcomes are 12-months death, myocardial infarction or acute revascularization, percentage discharged after 3 and 6 h, total length of hospital stay and all costs related to hospital contact within 12 months., Conclusion: Results from this study may facilitate implementation of POC hs-cTn testing assays and accelerated diagnostic protocols in EDs, and may serve as a valuable resource for guiding future investigations for the use of POC high sensitivity troponin assays in outpatient clinics and prehospital settings.

Objectives . Perioperative myocardial injury (PMI) is increasingly recognised as an important complication of non-cardiac surgery, with often clinically silent presentation, but detrimental prognosis. Active screening for PMI, involving the detection of dynamic and elevated levels of cardiac troponin, has recently been advocated by an increasing number of guidelines; however, active PMI screening has not been reflected in clinical practice. Design . As consensus on a common screening and management pathway is lacking, we synthesise the current evidence to provide suggestions on the selection of patients for screening, organisation of a screening program, and a potential management pathway, building upon a recently published perioperative screening algorithm. Results . Screening should be performed using high-sensitivity assays both preoperatively and postoperatively (postoperative Days 1 and 2) in patients at high-risk of experiencing perioperative complications. Conclusion . This expert opinion piece by an interdisciplinary group of predominantly Norwegian clinicians aims to assist healthcare professionals planning to implement guideline-recommended PMI screening at a local level in order to improve patient outcomes following non-cardiac surgery.

Objectives: 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., Methods: 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., Results: 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., Conclusions: 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., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

The term "single-sample rule-out" refers to the ability of very low concentrations of high-sensitivity cardiac troponin (hs-cTn) on presentation to exclude acute myocardial infarction with high clinical sensitivity and negative predictive value. Observational and randomized studies have confirmed this ability. Some guidelines endorse use of a concentration of hs-cTn at the assay's limit of detection, while other studies have validated the use of higher concentrations, allowing this approach to identify a greater proportion of patients at low risk. In most studies, at least 30% of patients can be triaged with this approach. The concentration of hs-cTn varies according to the assay used and sometimes how regulations permit reporting. It is clear that patients need to be at least 2 hours from the onset of symptoms being evaluated. Caution is warranted, particularly with older patients, women, and patients with underlying cardiac comorbidities., Competing Interests: Funding Support and Author Disclosures Dr Mills is supported by the British Heart Foundation through a Chair Award (CH/F/21/90010), a Programme Grant (RG/20/10/34966), and a Research Excellent Award (RE/18/5/34216). Dr Jaffe has consulted for Abbott, Beckman Coulter, Siemens, Roche, Ortho Diagnostics, ET Healthcare, SphingoTec, Radiometer, SpinChip, LumiraDX, Astellas, Amgen, Novartis, and RCE Technologies; and holds patent 20210401347 along with others. Dr Body has received consulting fees from Roche, Aptamer Group, Abbott, Psyros Diagnostics, Siemens Healthineers, Beckman Coulter, and Radiometer; and has participated on advisory boards for the FORCE Trial (funded by the National Institute for Health and Care Research), the REWIRE trial (Queen Mary University), the PRONTO trial (funded by the National Institute for Health and Care Research), and LumiraDx. Dr Mills has received research grants from Abbott Diagnostics and Siemens Healthineers; and has received personal fees for participation on advisory boards or speaking from Abbott Diagnostics, Roche Diagnostics, Siemens Healthineers, LumiraDx, and Psyros Diagnostics. Dr Aakre is an associate editor of Clinical Biochemistry; is chair of the International Federation of Clinical Chemistry and Laboratory Medicine Committee on Clinical Applications of Cardiac Bio-Markers; has served on advisory boards for Roche Diagnostics and SpinChip; has received consulting honoraria from CardiNor; has received lecture honorarium from Siemens Healthineers and Snibe Diagnostics; and has received research grants from Siemens Healthineers and Roche Diagnostics. Dr Collinson is an associate editor of the Journal of Applied Laboratory Medicine; is an advisory board member for Psyros Diagnostics; and has previously advised LumiraDX, Radiometer, and Siemens. Dr Saenger has received consulting fees from Radiometer. Dr Hammarsten has stock options with Aligned Bio. Dr Omland has received consulting fees from Roche, Bayer, and CardiNor; has received honoraria from Roche; has a patent pending with Roche; has participated on advisory boards for Bayer and Roche; has a fiduciary role with CardiNor; holds stock in CardiNor; and has received equipment and material from Novartis and Abbott. Dr Sandoval has been on advisory boards and has served as a speaker for Abbott Diagnostics and Roche Diagnostics; and holds patent 20210401347 along with others. Dr Ordonez-Llanos has received consulting fees from AWE Medical and Hemcheck. Dr Apple has received consulting fees from HyTest and AWE Medical; has received advisory fees from Werfen, Siemens Healthineers, and Qorvo Biotechnology; has received nonsalaried grant support through the Hennepin Healthcare Research Institute from Abbott Diagnostics, Abbott POC, Roche Diagnostics, Siemens Healthineers, Quidel/Ortho, Becton Dickinson, and Beckman Coulter; and has received fees for serving as associate editor for Clinical Chemistry. Dr Wereski has reported that he has no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Acute chest pain is associated with an increased risk of death and cardiovascular events even when acute myocardial infarction (AMI) has been excluded. Growth differentiation factor-15 (GDF-15) is a strong prognostic marker in patients with acute chest pain and AMI, but the prognostic value in patients without AMI is uncertain. This study sought to investigate the ability of GDF-15 to predict long-term prognosis in patients presenting with acute chest pain without AMI., Methods: In total, 1320 patients admitted with acute chest pain without AMI were followed for a median of 1523 days (range: 4 to 2208 days). The primary end point was all-cause mortality. Secondary end points included cardiovascular (CV) death, future AMI, heart failure hospitalization, and new-onset atrial fibrillation (AF)., Results: Higher concentrations of GDF-15 were associated with increased risk of death from all causes (median concentration in non-survivors vs survivors: 2124 pg/mL vs 852 pg/mL, P < 0.001), and all secondary end points. By multivariable Cox regression, GDF-15 concentration ≥4th quartile (compared to <4th quartile) remained an independent predictor of all-cause death (adjusted hazard ratio (HR): 2.75; 95% CI, 1.69-4.45, P < 0.001), CV death (adjusted HR: 3.74; 95% CI, 1.31-10.63, P = 0.013), and heart failure hospitalization (adjusted HR: 2.60; 95% CI, 1.11-6.06, P = 0.027). Adding GDF-15 to a model consisting of established risk factors and high-sensitivity cardiac troponin T (hs-cTnT) led to a significant increase in C-statistics for prediction of all-cause mortality., Conclusions: Higher concentrations of GDF-15 were associated with increased risk of mortality from all causes and risk of future CV events., (© American Association for Clinical Chemistry 2023.)

The International Federation of Clinical Chemistry Committee on Clinical Applications of Cardiac Biomarkers (IFCC C-CB) provides educational documents to facilitate the interpretation and use of cardiac biomarkers in clinical laboratories and practice. Our aim is to improve the understanding of certain key analytical and clinical aspects of cardiac biomarkers and how these may interplay. Measurements of cardiac troponin (cTn) have a prominent place in the clinical work-up of patients with suspected acute coronary syndrome. It is therefore important that clinical laboratories know how to recognize and assess analytical issues. Two emerging analytical issues resulting in falsely high cTn concentrations, often several fold higher than the upper reference limit (URL), are antibody-mediated assay interference due to long-lived cTn-antibody complexes, called macrotroponin, and crosslinking antibodies that are frequently referred to as heterophilic antibodies. We provide an overview of antibody-mediated cTn assay interference and provide recommendations on how to confirm the interference and interpret the results., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

The International Federation of Clinical Chemistry and Laboarator Medicine (IFCC) Committee on Clinical Applications of Cardiac Bio-Markers (C-CB) has provided evidence-based educational resources to aid and improve the understanding of important analytical and clinical aspects of cardiac biomarkers. The present IFCC C-CB educational report focuses on recommendations for appropriate use, analytical performance, and gaps in clinical studies related to the use of cardiac troponin (cTn) by point of care (POC) measurement, often referred to as a point of care testing (POCT). The use of high-sensitivity (hs)-cTn POC devices in accelerated diagnostic protocols used in emergency departments or outpatient clinics investigating acute coronary syndrome has the potential for improved efficacy, reduction of length of stay and reduced costs in the health care system. POCT workflow integration includes location of the instrument, assignment of collection and testing responsibility to (non-lab) staff, instrument maintenance, in-service and recurrent training, quality control, proficiency assessments, discrepant result trapping, and troubleshooting and inventory management., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Biological variation (BV) data may be used to develop analytical performance specifications (APS), reference change values (RCV), and support the applicability of population reference intervals. This study estimates within-subject BV (CVI) for several endocrine biomarkers using 3 different methodological approaches., Methods: For the direct method, 30 healthy volunteers were sampled weekly for 10 consecutive weeks. Samples were analyzed in duplicate for 17-hydroxyprogesterone (17-OHP), androstenedione, cortisol, cortisone, estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), and testosterone. A CV-ANOVA with outlier removal and a Bayesian model were applied to derive the CVI. For estradiol, FSH and LH, only the male subgroup was included. In the indirect method, using the same analytes and groups, pairs of sequential results were extracted from the laboratory information system. The total result variation for individual pairs was determined by identifying a central gaussian distribution in the ratios of the result pairs. The CVI was then estimated by removing the effect of analytical variation., Results: The estimated CVI from the Bayesian model (μCVP(i)) in the total cohort was: 17-OHP, 23%; androstenedione, 20%; cortisol, 18%; cortisone, 11%; SHBG, 7.4%; testosterone, 16%; and for the sex hormones in men: estradiol, 14%; FSH, 8%; and LH, 26%. CVI-heterogeneity was present for most endocrine markers. Similar CVI data were estimated using the CV-ANOVA and the indirect method., Conclusions: Similar CVI data were obtained using 2 different direct and one indirect method. The indirect approach is a low-cost alternative ensuring implementation of CVI data applicable for local conditions., (© American Association for Clinical Chemistry 2022.)

The International Federation of Clinical Chemistry Committee on Clinical Application of Cardiac Bio-Markers provides evidence-based educational documents to facilitate uniform interpretation and utilization of cardiac biomarkers in clinical laboratories and practice. The committee's goals are to improve the understanding of certain key analytical and clinical aspects of cardiac biomarkers and how these may interplay in clinical practice. Measurement of high-sensitivity cardiac troponin (hs-cTn) assays is a cornerstone in the clinical evaluation of patients with symptoms and/or signs of acute cardiac ischemia. To define myocardial infarction, the Universal Definition of Myocardial Infarction requires patients who manifest with features suggestive of acute myocardial ischemia to have at least one cTn concentration above the sex-specific 99th percentile upper reference limit (URL) for hs-cTn assays and a dynamic pattern of cTn concentrations to fulfill the diagnostic criteria for MI. This special report provides an overview of how hs-cTn 99th percentile URLs should be established, including recommendations about prescreening and the number of individuals required in the reference cohort, how statistical analysis should be conducted, optimal preanalytical and analytical protocols, and analytical/biological interferences or confounds that can affect accurate determination of the 99th percentile URLs. This document also provides guidance and solutions to many of the issues posed., (American Association for Clinical Chemistry 2022.)

Objective: To describe the magnitude and predictors of symptom burden (SB) and quality of life (QoL) 3 months after hospital admission for acute chest pain., Design: Prospective observational study., Setting: Single centre, outpatient follow-up., Participants: 1506 patients., Outcomes: Scores reported for general health (RAND-12), angina-related health (Seattle Angina Questionnaire 7 (SAQ-7)) and dyspnoea (Rose Dyspnea Scale) 3 months after hospital admission for chest pain., Methods: A total of 1506 patients received questionnaires assessing general health (RAND-12), angina-related health (SAQ-7) and dyspnoea (Rose Dyspnea Scale) 3 months after discharge. Univariable and multivariable regression models identified predictors of SB and QoL scores. A mediator analysis identified factors mediating the effect of an unstable angina pectoris (UAP) diagnosis., Results: 774 (52%) responded. Discharge diagnoses were non-ST elevation myocardial infarction (NSTEMI) (14.2%), UAP (17.1%), non-coronary cardiac disease (6.6%), non-cardiac disease (6.3%) and non-cardiac chest pain (NCCP) (55.6%). NSTEMI had the most favourable, and UAP patients the least favourable SAQ-7 scores (median SAQ7-summary; 88 vs 75, p<0.001). NCCP patients reported persisting chest pain in 50% and dyspnoea in 33% of cases. After adjusting for confounders, revascularisation predicted better QoL scores, while UAP, current smoking and hypertension predicted worse outcome. NSTEMI and UAP patients who were revascularised reported higher scores (p<0.05) in SAQ-7-QL, SAQ7-PL, SAQ7-summary (NSTEMI) and all SAQ-7 domains (UAP). Revascularisation altered the unstandardised beta value (>±10%) of an UAP diagnosis for all SAQ-7 and RAND-12 outcomes., Conclusions: Patients with NSTEMI reported the most favourable outcome 3 months after hospitalisation for chest pain. Patients with other diseases, in particular UAP patients, reported lower scores. Revascularised NSTEMI and UAP patients reported higher QoL scores compared with patients receiving conservative treatment. Revascularisation mediated all outcomes in UAP patients., Trial Registration Number: NCT02620202., Competing Interests: Competing interests: KMA has served on one advisory board for Roche Diagnostics and received lecturing fees from Siemens Healthineers. TO has served on advisory boards for Abbott Diagnostics, Roche Diagnostics and Bayer and has received research support from Abbott Diagnostics, Novartis, Roche Diagnostics, Singulex and SomaLogic via Akershus University Hospital, and speaker’s or consulting honoraria from Roche Diagnostics, Siemens Healthineers and CardiNor. NS, TMN, O-TS, HLT, JL, ROB, ØS, VVSB, ØRM and KV have nothing to declare., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Evaluate the association between symptoms and risk of non-ST segment elevation myocardial infarction (NSTEMI) in patients admitted to an emergency department with suspected acute coronary syndrome based on sex and age., Design: Post hoc analysis of a prospective observational study conducted between September 2015 and May 2019., Setting: University hospital in Norway., Participants: 1506 participants >18 years of age (39.6% women and 31.0% 70 years of age or older)., Findings: The OR for NSTEMI was 9.4 if pain radiated to both arms, 3.0 if exertional chest pain was present during the last week and 2.9 if pain occurred during activity. Men had significantly lower OR compared with women if pain was dependent of position, respiration or palpation (OR 0.17 vs 0.53, p value for interaction 0.047). Patients <70 years had higher predictive value than older patients if they reported exertional chest pain the last week (OR 4.08 vs 1.81, 95%, p value for interaction 0.025) and lower if pain radiated to the left arm (OR 0.73 vs 1.67, p value for interaction 0.045)., Conclusions: Chest pain with radiation to both arms, exertional chest pain during the last week and pain during activity had the strongest predictive value for NSTEMI. The differences in symptom presentation and risk of NSTEMI between sex and age groups were small., Trial Registration Number: WESTCOR study ClinicalTrials.gov (NCT02620202)., Competing Interests: Competing interests: KMA has served on one advisory board for Roche Diagnostics and received lecturing fees from Siemens Healthineers. TO has received nonfinancial support to institution from Novartis, Abbott Diagnostics, Roche Diagnostics and Somalogic, received consulting fees from Roche Diagnostics, Abbott Diagnostics and CardiNor, received speaker’s honoraria from Siemens Healthineers, Roche Diagnostics and Abbott Diagnostics, is a member of IFCC Committee on Cardiovascular Biomarkers and has stocks in CardiNor. ØS has received lecture fees from Abbott Diagnostics., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: This study tested the hypothesis that combining stress-induced biomarkers (copeptin or glucose) with high-sensitivity cardiac troponin (hs-cTn) increases diagnostic accuracy for non-ST-elevation myocardial infarction (NSTEMI) in patients presenting to the emergency department., Methods and Results: The ability to rule-out NSTEMI for combinations of baseline hs-cTnT or hs-cTnI with copeptin or glucose was compared with the European Society of Cardiology (ESC) hs-cTnT/I-only rule-out algorithms in two independent (one Norwegian and one international multicentre) diagnostic studies. Among 959 patients (median age 64 years, 60.5% male) with suspected NSTEMI in the Norwegian cohort, 13% had NSTEMI. Adding copeptin or glucose to hs-cTnT/I as a continuous variable did not improve discrimination as quantified by the area under the curve {e.g. hs-cTnT/copeptin 0.91 [95% confidence interval (CI) 0.89-0.93] vs. hs-cTnT alone 0.91 (95% CI 0.89-0.93); hs-cTnI/copeptin 0.85 (95% CI 0.82-0.87) vs. hs-cTnI alone 0.93 (95% CI 0.91-0.95)}, nor did adding copeptin <9 mmol/L or glucose <5.6 mmol/L increase the sensitivity of the rule-out provided by hs-cTnT <5 ng/L or hs-cTnI <4 ng/L in patients presenting more than 3 h after chest pain onset (target population in the ESC-0 h-algorithm). The combination decreased rule-out efficacy significantly (both P < 0.01). These findings were confirmed among 1272 patients (median age 62 years, 69.3% male) with suspected NSTEMI in the international validation cohort, of which 20.7% had NSTEMI. A trend towards increased sensitivity for the hs-cTnT/I/copeptin combinations (97-100% vs. 91-97% for the ESC-0 h-rule-out cut-offs) was observed in the Norwegian cohort., Conclusion: Adding copeptin or glucose to hs-cTnT/I did not increase diagnostic performance when compared with current ESC guideline hs-cTnT/I-only 0 h-algorithms., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The European Society of Cardiology (ESC) rule-out algorithms use cutoffs optimized for exclusion of non-ST elevation myocardial infarction (NSTEMI). We investigated these and several novel algorithms for the rule-out of non-ST elevation acute coronary syndrome (NSTE-ACS) including less urgent coronary ischemia., Method: A total of 1504 unselected patients with suspected NSTE-ACS were included and divided into a derivation cohort (n = 988) and validation cohort (n = 516). The primary endpoint was the diagnostic performance to rule-out NSTEMI and unstable angina pectoris during index hospitalization. The secondary endpoint was combined MI, all-cause mortality (within 30 days) and urgent (24 h) revascularization. The ESC algorithms for high-sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI) were compared to different novel low-baseline (limit of detection), low-delta (based on the assay analytical and biological variation), and 0-1-h and 0-3-h algorithms., Results: The prevalence of NSTE-ACS was 24.8%, 60.0% had noncardiac chest pain, and 15.2% other diseases. The 0-1/0-3-h algorithms had superior clinical sensitivity for the primary endpoint compared to the ESC algorithm (validation cohort); hs-cTnT: 95% vs 63%, and hs-cTnI: 87% vs 64%, respectively. Regarding the secondary endpoint, the algorithms had similar clinical sensitivity (100% vs 94%-96%) but lower clinical specificity (41%-19%) compared to the ESC algorithms (77%-74%). The rule-out rates decreased by a factor of 2-4., Conclusion: Low concentration/low-delta troponin algorithms improve the clinical sensitivity for a combined endpoint of NSTEMI and unstable angina pectoris, with the cost of a substantial reduction in total rule-out rate. There was no clear benefit compared to ESC for diagnosing high-risk events., (© American Association for Clinical Chemistry 2021.)

Background: Secretoneurin is a novel prognostic biomarker that may predict mortality in heart failure and the occurrence of ventricular arrhythmias. This study reports the within subject variation (CV I ), between subject variation (CV G ), reference change values (RCV) and index of individuality (II) of secretoneurin., Methods: Thirty healthy volunteers were included. Non-fasting samples were obtained between 8 and 10 am once a week for ten weeks. Secretoneurin was analyzed in duplicate using ELISA. No outliers were present according to Burnett and Reeds' criteria. Simple linear regression did not identify significant trends. Variance homogeneity in the analytical variance and CV I were tested using Cochrane's and Bartlett's tests and four participants were excluded. Calculation of CV I , CV G and RCV were done on ln transformed data as described by Fokkema, the II was calculated using retransformed data., Results: The median age of the participants was 36 years and 53% were female. Non-fasting glucose, eGFR (CKD-EPI) , cTnT and NT-proBNP concentrations were within the normal range. Median secretoneurin concentrations were 38 pmol/L (women) and 33 pmol/L (men), p-value < 0.001. CV I and CV G were 9.8% (CI 8.7% to 11.0%) and 20.0 (CI 15.4% to 28.0%), respectively. RCV were 38.7% (CI 35.5% to 42.7%) and -27.9 (CI -29.9 to -26.2) and the II were 0.60 (CI 0.42-0.78). No gender differences were present., Conclusion: Secretoneurin has a fairly low CV I , CV G , RCV and II, indicating that it could be suitable as a diagnostic or prognostic biomarker and that delta values in serial samplings may be preferable for identifying clinical changes., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background Postexercise cardiac troponin levels show considerable interindividual variations. This study aimed to identify the major determinants of this postexercise variation in cardiac troponin I (cTnI) following 3 episodes of prolonged high-intensity endurance exercise. Methods and Results Study subjects were recruited among prior participants in a study of recreational cyclists completing a 91-km mountain bike race in either 2013 or 2014 (first race). In 2018, study participants completed a cardiopulmonary exercise test 2 to 3 weeks before renewed participation in the same race (second race). Blood was sampled before and at 3 and 24 hours following all exercises. Blood samples were analyzed using the same Abbot high-sensitivity cTnI STAT assay. Fifty-nine individuals (aged 50±9 years, 13 women) without cardiovascular disease were included. Troponin values were lowest before, highest at 3 hours, and declining at 24 hours. The largest cTnI difference was at 3 hours following exercise between the most (first race) (cTnI: 200 [87-300] ng/L) and the least strenuous exercise (cardiopulmonary exercise test) (cTnI: 12 [7-23] ng/L; P <0.001). The strongest correlation between troponin values at corresponding times was before exercise ( r =0.92, P <0.0001). The strongest correlations at 3 hours were between the 2 races ( r =0.72, P <0.001) and at 24 hours between the cardiopulmonary exercise test and the second race ( r =0.83, P <0.001). Participants with the highest or lowest cTnI levels showed no differences in race performance or baseline echocardiographic parameters. Conclusions The variation in exercise-induced cTnI elevation is largely determined by a unique individual cTnI response that is dependent on the duration of high-intensity exercise and the timing of cTnI sampling. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02166216.

Background: The CARdiac MARker Guideline Uptake in Europe (CAMARGUE) program is a multi-country audit of the use of cardiac biomarkers in routine clinical practice., Methods: An email link to a web-based questionnaire of 30 multiple-choice questions was distributed via the professional societies in Europe., Results: 374 questionnaires were returned from 39 countries, the majority of which were in northern Europe with a response rate of 8.2%-42.0%. The majority of the respondents were from hospitals with proportionately more responses from central hospitals than district hospitals. Cardiac troponin was the preferred cardiac biomarker, evenly split between cardiac troponin T (cTnT) and cardiac troponin I (cTnI). Aspartate transaminase and lactate dehydrogenase are no longer offered as cardiac biomarkers. Creatine kinase, creatine kinase MB isoenzyme, and myoglobin continue to be offered as part of the cardiac biomarker profile in approximately on 50% of respondents. There is widespread utilization of high sensitivity (hs) troponin assays. The majority of cTnT users measure hs-cTnT. 29.5% of laboratories measure cTnI by a non-hs method but there has been substantial conversion to hs-cTnI. The majority of respondents used ng/L and use the 99th percentile as the upper reference limit (71.9% of respondents). A range of diagnostic protocols are in use., Conclusions: There is widespread utilization of hs troponin methods. A significant minority do not use the 99th percentile as recommended and there is, as yet, little uptake of very rapid diagnostic strategies. Education of laboratory professionals and clinicians remains a priority., (© American Association for Clinical Chemistry 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Dietary supplement use among recreational athletes is common, with the intention of reducing inflammation and improving recovery. We aimed to describe the relationship between omega-3 fatty acid supplement use and inflammation induced by strenuous exercise., Methods: C-reactive protein (CRP) concentrations were measured in 1002 healthy recreational athletes before and 24 h after a 91-km bicycle race. The use of omega-3 fatty acid supplements was reported in 856 out of 1002 recreational athletes, and the association between supplement use and the exercise-induced CRP response was assessed., Results: Two hundred seventy-four subjects reported regular use of omega-3 fatty acid supplements. One hundred seventy-three of these used cod liver oil (CLO). Regular users of omega-3 fatty acid supplements had significantly lower basal and exercise-induced CRP levels as compared to non-users (n = 348, p < 0.001). Compared to non-users, regular users had a 27% (95% confidence interval (CI): 14-40) reduction in Ln CRP response (unadjusted model, p < 0.001) and 16% (95% CI: 5-28, p = 0.006) reduction after adjusting for age, sex, race duration, body mass index, delta creatine kinase, MET hours per week, resting heart rate and higher education. CLO was the primary driver of this response with a 34% (95% CI: 19-49) reduction (unadjusted model, p < 0.001) compared to non-users. Corresponding numbers in the adjusted model were 24% (95% CI: 11-38, p < 0.001)., Conclusion: Basal CRP levels were reduced, and the exercise-induced CRP response was attenuated in healthy recreational cyclists who used omega-3 fatty acid supplements regularly. This effect was only present in regular users of CLO., Trial Registration: NCT02166216 , registered June 18, 2014 - Retrospectively registered.

Objectives: Cardiac myosin-binding protein C (cMyC) is a novel biomarker of myocardial injury, with a promising role in the triage and risk stratification of patients presenting with acute cardiac disease. In this study, we assess the weekly biological variation of cMyC, to examine its potential in monitoring chronic myocardial injury, and to suggest analytical quality specification for routine use of the test in clinical practice., Methods: Thirty healthy volunteers were included. Non-fasting samples were obtained once a week for ten consecutive weeks. Samples were tested in duplicate on the Erenna ® platform by EMD Millipore Corporation. Outlying measurements and subjects were identified and excluded systematically, and homogeneity of analytical and within-subject variances was achieved before calculating the biological variability (CV I and CV G ), reference change values (RCV) and index of individuality (II)., Results: Mean age was 38 (range, 21-64) years, and 16 participants were women (53%). The biological variation, RCV and II with 95% confidence interval (CI) were: CV A (%) 19.5 (17.8-21.6), CV I (%) 17.8 (14.8-21.0), CV G (%) 66.9 (50.4-109.9), RCV (%) 106.7 (96.6-120.1)/-51.6 (-54.6 to -49.1) and II 0.42 (0.29-0.56). There was a trend for women to have lower CV G. The calculated RCVs were comparable between genders., Conclusions: cMyC exhibits acceptable RCV and low II suggesting that it could be suitable for disease monitoring, risk stratification and prognostication if measured serially. Analytical quality specifications based on biological variation are similar to those for cardiac troponin and should be achievable at clinically relevant concentrations., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Aims: Troponin-based algorithms are made to identify myocardial infarctions (MIs) but adding either standard acute coronary syndrome (ACS) risk criteria or a clinical risk score may identify more patients eligible for early discharge and patients in need of urgent revascularization., Methods and Results: Post-hoc analysis of the WESTCOR study including 932 patients (mean 63 years, 61% male) with suspected NSTE-ACS. Serum samples were collected at 0, 3, and 8-12 h and high-sensitivity cTnT (Roche Diagnostics) and cTnI (Abbott Diagnostics) were analysed. The primary endpoint was MI, all-cause mortality, and unplanned revascularizations within 30 days. Secondary endpoint was non-ST-elevation myocardial infarction (NSTEMI) during index hospitalization. Two combinations were compared: troponin-based algorithms (ESC 0/3 h and the High-STEACS algorithm) and either ACS risk criteria recommended in the ESC guidelines, or one of eleven clinical risk scores, HEART, mHEART, CARE, GRACE, T-MACS, sT-MACS, TIMI, EDACS, sEDACS, Goldman, and Geleijnse-Sanchis. The prevalence of primary events was 21%. Patients ruled out for NSTEMI and regarded low risk of ACS according to ESC guidelines had 3.8-4.9% risk of an event, primarily unplanned revascularizations. Using HEART score instead of ACS risk criteria reduced the number of events to 2.2-2.7%, with maintained efficacy. The secondary endpoint was met by 13%. The troponin-based algorithms without evaluation of ACS risk missed three-index NSTEMIs with a negative predictive value (NPV) of 99.5% and 99.6%., Conclusion: Combining ESC 0/3 h or the High-STEACS algorithm with standardized clinical risk scores instead of ACS risk criteria halved the prevalence of rule-out patients in need of revascularization, with maintained efficacy., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Morbid obesity is a risk factor for cardiovascular disease. The relative effects of Roux-en-Y gastric bypass surgery (GBS) and intensive lifestyle intervention (ILI) on subclinical myocardial injury, the activity of the cardiac natriuretic system, and systemic inflammation remain unclear., Methods: In a 59-week non-randomized clinical trial that included 131 patients with morbid obesity, we compared the effects ofGBS and ILI on concentrations of cardiac troponin T (cTnT) and I (cTnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and C-reactive protein (CRP)., Results: In the GBS and ILI group, median body mass index (BMI) was reduced by 14.4 kg/m 2 versus 3.9 kg/m 2 , respectively (p value < 0.001). Cardiac troponins decreased after GBS, p = 0.014 (cTnT) and p = 0.065 (cTnI) and increased significantly in those treated with ILI (p values ≤ 0.021) (between-group differences for deltas: p ≤ 0.003). NT-proBNP increased in both groups, but significantly more in the GBS than in the ILI group (between-group differences for deltas: p = 0.008). CRP decreased significantly within the GBS and the ILI group, with this change significantly greater in the GBS group (between-group differences for deltas p < 0.001). The dominating mediator of the biomarker changes was weight loss. Prior coronary artery disease and diabetes were predictive of the magnitude of the changes in cTnI and NT-proBNP, respectively., Conclusion: Compared to ILI, GBS was associated with reduced subclinical myocardial injury and systemic inflammation, and enhancement of the cardiac natriuretic peptide system. The biomarker changes were predominantly mediated by weight loss., (Copyright © 2020. Published by Elsevier Inc.)

Background: The European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) initiated the CArdiac MARker Guidelines Uptake in Europe (CAMARGUE) Study to survey if current biomarker testing for heart failure (HF) in Europe is in accordance with up-dated guidelines., Methods: A web-based questionnaire was distributed to clinical laboratories via European biochemical societies in 2019. Questions covered the type of natriuretic peptide (NP) assays performed, decision limits for HF, and opinion concerning requirement of different thresholds in patients with renal failure or obesity., Results: There were 347 participating laboratories mostly from European countries with 266 offering NP testing. NP testing was increased from 67% to 77% between 2013 and 2019. NT-proBNP remained the preferred biomarker. Recommended decision limits were implemented for BNP (85%) and better focused for NT-proBNP (40%) than in the previous survey. The survey revealed that laboratorians are willing to support the translation of adjusted cut-off values for age, gender and for patients with conditions like renal insufficiency., Conclusion: Guidelines stimulate clinical laboratories to offer NP testing with high value for the diagnosis and management of HF, and to present adjusted medical decision limits. Future guidelines should encourage the use of personalized cut-offs for some confounding factors., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background Cardiac troponin (cTn) permits early rule-out/rule-in of patients admitted with possible non-ST-segment-elevation myocardial infarction. In this study, we developed an admission and a 0/1 hour rule-out/rule-in algorithm for a troponin assay with measurable results in >99% of healthy individuals. We then compared its diagnostic and long-term prognostic properties with other protocols. Methods and Results Blood samples were collected at 0, 1, 3, and 8 to 12 hours from patients admitted with possible non-ST-segment-elevation myocardial infarction. cTnT (Roche Diagnostics), cTnI (Abbott) (Abbott Diagnostics), and cTnI (sgx) (Singulex Clarity System) were measured in 971 admission and 465 1-hour samples. An admission and a 0/1 hour rule-out/rule-in algorithm were developed for the cTnI (sgx) assay and its diagnostic properties were compared with cTnT ESC (European Society of Cardiology), cTnI (Abbott)ESC , and 2 earlier cTnI (sgx) algorithms. The prognostic composite end point was all-cause mortality and future nonfatal myocardial infarction during a median follow-up of 723 days. non-ST-segment-elevation myocardial infarction prevalence was 13%. The novel cTnI (sgx) algorithms showed similar performance regardless of time from symptom onset, and area under the curve was significantly better than comparators. The cTnI (sgx)0/1 hour algorithm classified 92% of patients to rule-in or rule-out compared with ≤78% of comparators. Patients allocated to rule-out by the prior published 0/1 hour algorithms had significantly fewer long-term events compared with the rule-in and observation groups. The novel cTnI (sgx)0/1 hour algorithm used a higher troponin baseline concentration for rule-out and did not allow for prognostication. Conclusions Increasingly sensitive troponin assays may improve identification of non-ST-segment-elevation myocardial infarction but could rule-out patients with subclinical chronic myocardial injury. Separate protocols for diagnosis and risk prediction seem appropriate.

Objectives: There are many mobile health applications (apps) now available and some that use in some way laboratory medicine data. Among them, patient-oriented are of the lowest content quality. The aim of this study was to compare the opinions of non-laboratory medicine professionals (NLMP) with those of laboratory medicine specialists (LMS) and define the benchmarks for quality assessment of laboratory medicine apps., Methods: Twenty-five volunteers from six European countries evaluated 16 selected patient-oriented apps. Participants were 20-60 years old, 44% were females, with different educational degrees, and no professional involvement in laboratory medicine. Each participant completed a questionnaire based on the Mobile Application Rating Scale (MARS) and the System Usability Scale, as previously used for rating the app quality by LMS. The responses from the two groups were compared using the Mann-Whitney U test and Spearman correlation., Results: The median total score of NLMP app evaluation was 2.73 out of 5 (IQR 0.95) compared to 3.78 (IQR 1.05) by the LMS. All scores were statistically significantly lower in the NLMP group (p<0.05), except for the item Information quality (p=0.1631). The suggested benchmarks for a useful appear: increasing awareness of the importance and delivering an understanding of persons' own laboratory test results; understandable terminology; easy to use; appropriate graphic design, and trustworthy information., Conclusions: NLMP' evaluation confirmed the low utility of currently available laboratory medicine apps. A reliable app should contain trustworthy and understandable information. The appearance of an app should be fit for purpose and easy to use., (© 2020 Walter de Gruyter GmbH, Berlin/Boston.)

Background Use of snus, a smokeless tobacco product, is increasing in Scandinavia. Strenuous physical activity is associated with an acute increase in high-sensitivity cardiac troponin (swhs-cTn) concentrations. Current smoking is associated with lower hs-cTn, but whether this also holds true for smokeless tobacco and whether tobacco affects the hs-cTn response to exercise remain unknown. Methods and Results We measured hs-cTnI and hs-cTnT concentrations in 914 recreational athletes before and 3 and 24 hours after a 91-km bicycle race. Self-reported snus tobacco habits were reported as noncurrent (n=796) and current (n=118). The association between snus use and change in log-transformed hs-cTnI and hs-cTnT concentrations (ie, the differences between concentrations at baseline and 3 hours and 24 hours ) were assessed by multivariable linear regression analysis. Concentrations of hs-cTn at baseline were lower in current than in noncurrent snus users (hs-cTnI median, 1.7 ng/L; Q1 to Q3: 1.6-2.3 versus 2.0 ng/L; Q1 to Q3: 1.6-3.2 [ P =0.020]; and hs-cTnT: median, 2.9 ng/L, Q1 to Q3: 2.9-3.5 versus 2.9 ng/L, Q1 to Q3: 2.9-4.3 [ P =0.021]). In fully adjusted multivariable models, use of snus was associated with lower change in hs-cTn concentrations from baseline to 3 hours (hs-cTnI: -29% [ P =0.002], hs-cTnT: -18% [ P =0.010]) and 24 hours (hscTnI: -30% [ P =0.010], hs-cTnT -19%, [ P =0.013]). Conclusions Resting hs-cTn concentrations are lower and the exercise-induced cardiac troponin response is attenuated in current users of smokeless tobacco compared with nonusers. Further insight into the pathophysiological processes underlying the attenuated cardiac troponin response to exercise in tobacco users is needed. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT02166216.

Concurrent with the introduction of cardiac troponin measurements into the diagnostic definition of myocardial infarction (MI), clinicians and laboratory professionals signaled a clear clinical need for improved analytical quality. This was an important precipitant for developing high-sensitivity cardiac troponin (hs-cTn) assays, currently used in rapid algorithms guiding investigations of patients presenting to the emergency department with possible MI. The hs-cTn assays were also important for the detection and monitoring of low-grade chronic myocardial injury, a condition that has been linked to increased long-term risk of cardiovascular morbidity and mortality. This review summarizes the general recommendations for defining analytical performance specifications while providing relevant clinical situations related to analytical performance. Importantly, outcome studies suggest analytical quality performance for hs-cTn is sufficient for early discharge of patients investigated for possible MI. However, bias due to change in calibrators or reagents may significantly affect the percentage of patients discharged. Biological variation data is suitable for defining performance specifications when hs-cTn measurements are used for diagnosing and monitoring chronic myocardial injury. Further improvement in analytical performance for hs-cTn testing may result in even faster decision making in the emergency setting; while also identifying those with chronic injury at risk for an adverse cardiac event., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The CArdiac MARker Guidelines Uptake in Europe Study (CAMARGUE) initiated by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) aims to survey the current use of evidence-based guidelines for dyslipidemia testing in Europe., Methods: In 2019 a web-based questionnaire was distributed via EFLM National Societies to clinical laboratories in Europe. Questions covered pre-analytics, analytical methods, measurement units, flagging of decision thresholds, and use of decision-enhancing comments., Results: Returns were obtained from 452 laboratories from 28 countries. Most laboratories always use nonfasting blood samples for lipid assays (66%). Lipid profiles are reported in mmol/L by 59% of the laboratories, mainly from 14 countries promoting the use of SI units. Important differences in flagging of decision thresholds were observed, with less than half of the laboratories applying the guideline-recommended LDL cholesterol threshold. Only 17% of the laboratories add an alert comment when familial hypercholesterolemia is suspected and 23% when risk of pancreatitis from hypertriglyceridemia is high., Conclusions: There are marked differences among laboratories in Europe in terms of pre-analytical, analytical, and post-analytical lipid management that could have an important clinical impact. This relates to different availability of assays or different laboratory practices on reporting and flagging of lipid profiles., Competing Interests: Declaration of Competing Interest The authors have no other competing interests or conflicts of interest to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Higher concentrations of cardiac troponin T are associated with coronary artery disease (CAD) and adverse cardiovascular prognosis. The relation with incident atrial fibrillation (AF) is less explored. We studied this association among 3,568 patients evaluated with coronary angiography for stable angina pectoris without previous history of AF. The prospective association between high-sensitivity cardiac troponin T (hs-cTnT) categories (≤3 ng/L; n = 1,694, 4-9; n = 1,085, 10 to 19; n = 614 and 20 to 30; n = 175) and incident AF and interactions with the extent of CAD were studied by Kaplan-Meier plots and Cox regression. Risk prediction improvements were assessed by receiver operating characteristic area under the curve (ROC-AUC) analyses. During median (25 to 75 percentile) 7.3 (6.3 to 8.6) years of follow-up 412 (11.5%) were diagnosed with AF. In a Cox model adjusted for age, gender, body mass index, hypertension, diabetes mellitus, smoking, estimated glomerular filtration rate, and left ventricular ejection fraction, hazard ratios (HRs) (95% confidence intervals [CIs]) were 1.53 (1.16 to 2.03), 2.03 (1.49 to 2.78), and 2.15 (1.40 to 3.31) when comparing the second, third, and fourth to the first hs-cTnT group, respectively (P for trend <0.000001). The strongest association between hs-cTnT levels and incident AF was found among patients without obstructive CAD (P int  = 0.024) and adding hs-cTnT to established AF risk factors improved risk classification slightly (ΔROC 0.006, p = 0.044). In conclusion, in patients with suspected stable angina higher levels of hs-cTnT predicted increased risk of incident AF. This was most pronounced in patients without obstructive CAD suggesting an association not mediated by coronary disease., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Sudden cardiac death among middle-aged recreational athletes is predominantly due to myocardial ischaemia. This study examined whether measuring cardiac troponin I and T (cTnI and cTnT) after strenuous exercise could identify occult obstructive coronary artery disease., Design: Prospective observational study., Methods: Subjects were recruited from 1002 asymptomatic recreational cyclists completing a 91-km mountain bike race (North Sea Race Endurance Exercise Study). No subject had known cardiovascular disease or took cardiovascular medication. Blood samples were collected within 24 h before and 3 h and 24 h after the race. Coronary computed tomography angiography was performed in 80 participants with the highest post-exercise cTnI and in 40 reference subjects with moderately elevated cTnI values., Results: Study subjects ( N  = 120) were 45 (36-52) years old and 74% were male. There were similar demographics in the High-cTnI group and the Reference group. The cTn concentrations were highest at 3 h post-race: cTnI, 224 (125-304) ng/L; cTnT, 89 (55-124) ng/L. Nine subjects had obstructive coronary artery disease on coronary computed tomography angiography, eight of whom were High-cTnI responders. Two subjects had myocardial bridging, both High-cTnI responders. Troponin concentrations at 24 h post-race were higher in subjects with obstructive coronary artery disease than in the rest of the cohort ( n  = 109): cTnI, 151 (72-233) ng/L vs . 24 (19-82) ng/L, p  = 0.005; cTnT, 39 (25-55) ng/L vs . 20 (14-31) ng/L, p  = 0.002. The areas under the receiver operating characteristic curves for predicting obstructive coronary artery disease were 0.79, p  = 0.005 (cTnI) and 0.82, p  = 0.002 (cTnT)., Conclusion: In subjects with occult obstructive coronary artery disease there was a prolonged elevation of cTn following strenuous exercise.