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

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.

Prognostic value of growth differentiation factor-15 3 months after an acute chest pain admission.

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.

Aiming toWards Evidence baSed inTerpretation of Cardiac biOmarkers in patients pResenting with chest pain using Point of Care Testing (WESTCOR-POC): study design.

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.

Implementing screening for myocardial injury in non-cardiac surgery: perspectives of an ad-hoc interdisciplinary expert group.

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.

Sex Hormones and Adrenal Steroids: Biological Variation Estimated Using Direct and Indirect Methods.

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.

Erratum to 'The association between serum high-sensitivity cardiac troponin T and acute myocardial infarction in patients with suspected chronic coronary syndrome is modified by body mass index*,***' International Journal of Cardiology Cardiovascular Risk and Prevention. Volume 11, December 2021, 200,109.

[This corrects the article DOI: 10.1016/j.ijcrp.2021.200109.].

Predictors of long-term symptom burden and quality of life in patients hospitalised with chest pain: a prospective observational study.

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.

Association between symptoms and risk of non-ST segment elevation myocardial infarction according to age and sex in patients admitted to the emergency department with suspected acute coronary syndrome: a single-centre retrospective cohort study.

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).

Quality benchmarking of smartphone laboratory medicine applications: comparison of laboratory medicine specialists' and non-laboratory medicine professionals' evaluation.

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.

High-Sensitivity Cardiac Troponin I and T Response Following Strenuous Activity is Attenuated by Smokeless Tobacco: NEEDED (North Sea Race Endurance Exercise Study) 2014.

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.

Systemic Cardiac Troponin T Associated With Incident Atrial Fibrillation Among Patients With Suspected Stable Angina Pectoris.

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 (Pint = 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.

Duration of Elevated Heart Rate Is an Important Predictor of Exercise-Induced Troponin Elevation.

Background The precise mechanisms causing cardiac troponin (cTn) increase after exercise remain to be determined. The aim of this study was to investigate the impact of heart rate (HR) on exercise-induced cTn increase by using sports watch data from a large bicycle competition. Methods and Results Participants were recruited from NEEDED (North Sea Race Endurance Exercise Study). All completed a 91-km recreational mountain bike race (North Sea Race). Clinical status, ECG, blood pressure, and blood samples were obtained 24 hours before and 3 and 24 hours after the race. Participants (n=177) were, on average, 44 years old; 31 (18%) were women. Both cTnI and cTnT increased in all individuals, reaching the highest level (of the 3 time points assessed) at 3 hours after the race (P<0.001). In multiple regression models, the duration of exercise with an HR >150 beats per minute was a significant predictor of both cTnI and cTnT, at both 3 and 24 hours after exercise. Neither mean HR nor mean HR in percentage of maximum HR was a significant predictor of the cTn response at 3 and 24 hours after exercise. Conclusions The duration of elevated HR is an important predictor of physiological exercise-induced cTn elevation. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02166216.

Handling of hemolyzed serum samples in clinical chemistry laboratories: the Nordic hemolysis project.

Background Some clinical chemistry measurement methods are vulnerable to interference if hemolyzed serum samples are used. The aims of this study were: (1) to obtain updated information about how hemolysis affects clinical chemistry test results on different instrument platforms used in Nordic laboratories, and (2) to obtain data on how test results from hemolyzed samples are reported in Nordic laboratories. Methods Four identical samples containing different degrees of hemolysis were prepared and distributed to 145 laboratories in the Nordic countries. The laboratories were asked to measure the concentration of cell-free hemoglobin (Hb), together with 15 clinical chemistry analytes. In addition, the laboratories completed a questionnaire about how hemolyzed samples are handled and reported. Results Automated detection of hemolysis in all routine patient samples was used by 63% of laboratories, and 88% had written procedures on how to handle hemolyzed samples. The different instrument platforms measured comparable mean Hb concentrations in the four samples. For most analytes, hemolysis caused a homogenous degree of interference regardless of the instrument platform used, except for alkaline phosphatase (ALP), bilirubin (total) and creatine kinase (CK). The recommended cut-off points for rejection of a result varied substantially between the manufacturers. The laboratories differed in how they reported test results, even when they used the same type of instrument. Conclusions Most of the analytes were homogeneously affected by hemolysis, regardless of the instrument used. There is large variation, however, between the laboratories on how they report test results from hemolyzed samples, even when they use the same type of instrument.

Impact of different preanalytical conditions on results of lupus anticoagulant tests.

INTRODUCTION: The currently recommended preanalytical conditions for lupus anticoagulant (LA) analysis require analyzing samples in fresh or freshly frozen platelet-poor plasma. The aim of this study was to evaluate whether alternative and less cumbersome preanalytical procedures for LA testing give significantly different results compared to recommended conditions. MATERIALS AND METHODS: Citrated blood samples were drawn from 29 study participants, 15 with negative and 14 with positive LA results. The samples were processed according to the ISTH guideline for LA testing and compared to several alternative preanalytical conditions. Measurements were performed using the dilute Russell's viper venom time (DRVVT) and silica clotting time (SCT), both screen and confirm, on a STA-R Evolution analyzer. Stability criteria were based upon biological variation. RESULTS: All DRVVT tests (normalized screen, confirm, and screen/confirm ratio) met the stability criteria for all the preanalytical conditions. The SCT tests (normalized screen, confirm, and screen/confirm ratio) met the stability criteria only when treated according to the ISTH guideline, except for SCT normalized screen/confirm ratio which also met the stability criteria for double-centrifuged aliquoted plasma stored in room temperature for 24 hours and then analyzed "fresh" or after being frozen. One warfarin-treated patient was reclassified from positive to negative for DRVVT after the preanalytical modifications, while 2 of 29 participants became falsely positive for 2 of 8 conditions for SCT. CONCLUSIONS: The DRVVT assays met the criteria for stability for all preanalytical conditions tested, while the SCT assays should be interpreted with caution if the preanalytical guidelines from ISTH are not followed.