Clinical laboratory practice recommendations for high-sensitivity cardiac troponin testing

The role of cardiac troponins (cTn) have become increasingly important in diagnosing myocardial infarction (MI), especially in patients without electrocardiogram abnormalities (1)

Metformin and high-sensitivity cardiac troponin I and T trajectories in type 2 diabetes patients: a post-hoc analysis of a randomized controlled trial

Background: Metformin has favorable effects on cardiovascular outcomes in both newly onset and advanced type 2 diabetes, as previously reported findings from the UK Prospective Diabetes Study and the HOME trial have demonstrated. Patients with type 2 diabetes present with chronically elevated circulating cardiac troponin levels, an established predictor of cardiovascular endpoints and prognostic marker of subclinical myocardial injury. It is unknown whether metformin affects cardiac troponin levels. The study aimed to evaluate cardiac troponin I and T trajectories in patients with diabetes treated either with metformin or placebo. Methods: This study is a post-hoc analysis of a randomized controlled trial (HOME trial) that included 390 patients with advanced type 2 diabetes randomized to 850 mg metformin or placebo up to three times daily concomitant to continued insulin treatment. Cardiac troponin I and T concentrations were measured at baseline and after 4, 17, 30, 43 and 52 months. We evaluated cardiac troponin trajectories by linear mixed-effects modeling, correcting for age, sex, smoking status and history of cardiovascular disease. Results: This study enrolled 390 subjects, of which 196 received metformin and 194 received placebo. In the treatment and placebo groups, mean age was 64 and 59 years; with 50% and 58% of subjects of the female sex, respectively. Despite the previously reported reduction of macrovascular disease risk in this cohort by metformin, linear mixed-effects regression modelling did not reveal evidence for an effect on cardiac troponin I and cardiac troponin T levels [− 8.4% (− 18.6, 3.2), p = 0.150, and − 4.6% (− 12, 3.2), p = 0.242, respectively]. A statistically significant time-treatment interaction was found for troponin T [− 1.6% (− 2.9, − 0.2), p = 0.021] but not troponin I concentrations [− 1.5% (− 4.2, 1.2), p = 0.263]. Conclusions: In this post-hoc analysis of a 4.3-year randomized controlled trial, metformin did not exert a clinically relevant effect on cardiac troponin I and cardiac troponin T levels when compared to placebo. Cardioprotective effects of the drug observed in clinical studies are not reflected by a reduction in these biomarkers of subclinical myocardial injury. Trial registration ClinicalTrials.gov identifier NCT00375388

Prognostic value of basal high-sensitive cardiac troponin levels on mortality in the general population

Interest in the use of cardiac troponin T (cTnT) and cardiac troponin I (cTnI) has expanded from diagnosis of acute myocardial infarction to risk assessment for morbidity and mortality. Although cTnT and cTnI were shown to have equivalent diagnostic performance in the setting of suspected acute myocardial infarction, potential prognostic differences are largely unexplored. The aim of this study is to quantify and compare the relationship between cTnT and cTnI, and cardiovascular and all-cause mortality in the general population. Medline, Embase, and the Cochrane Library (from inception through October 2016) were searched for prospective observational cohort studies reporting on the prognostic value of basal high-sensitive cTnT and/or cTnI levels on cardiovascular and all-cause mortality in the general population. Data on study characteristics, participants' characteristics, outcome parameters, and quality [according to the Effective Public Health Practice Project (EPHPP) "Quality Assessment Tool For Quantitative Studies] were retrieved. Hazard ratios per standard deviation increase in basal cardiac troponin level (HR per 1-SD; retrieved from the included articles or estimated) were pooled using a random-effects model. On a total of 2585 reviewed citations, 11 studies, with data on 65,019 participants, were included in the meta-analysis. Random effects pooling showed significant associations between basal cardiac troponin levels and HR for cardiovascular and all-cause mortality [HR per 1-SD 1.29 (95% confidence interval, 95% CI, 1.20-1.38) and HR per 1-SD 1.18 (95% CI, 1.11-1.26), respectively]. Stratified analyses showed higher HRs for cTnT than cTnI [cardiovascular mortality: cTnT HR per 1-SD 1.37 (95% CI, 1.23-1.52); and cTnI HR per 1-SD 1.21 (95% CI, 1.16-1.26); all-cause mortality: cTnT HR per 1-SD 1.31 (955 CI, 1.13-1.53); and cTnI HR per 1-SD 1.14 (95% CI, 1.06-1.22)]. These differences were significant (P < 0.01) in meta-regression analyses for cardiovascular mortality but did not reach statistical significance for all-cause mortality. Elevated, basal cTnT, and cTnI show robust associations with an increased risk of cardiovascular and all-cause mortality during follow-up in the general population

Increased circulating desmosine and age-dependent elastinolysis in idiopathic pulmonary fibrosis

Abstract Although chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) seem to be opposite entities from a clinical perspective, common initial pathogenic steps have been suggested in both lung diseases. Emphysema is caused by an elastase/anti-elastase imbalance leading to accelerated elastin degradation. Elastinolysis is however, also accelerated in the IPF patients’ lungs. The amino acids desmosine and isodesmosine (DES) are unique to elastin. During the degradation process, elastases liberate DES from elastin fibers. Blood DES levels consequently reflect the rate of systemic elastinolysis and are increased in COPD. This is the first report describing elevated DES levels in IPF patients. We also demonstrated that the age-related increment of DES concentrations is enhanced in IPF. Our current study suggests that elastinolysis is a shared pathogenic step in both COPD and IPF. Further investigation is required to establish the relevance of accelerated elastin degradation in IPF and to determine whether decelerating this process leads to slower progression of lung fibrosis and better survival for patients with IPF.https://deepblue.lib.umich.edu/bitstream/2027.42/142803/1/12931_2018_Article_747.pd

The effect of exercise training on the course of cardiac troponin T and i levels: Three independent training studies

With the introduction of high-sensitive assays, cardiac troponins became potential biomarkers for risk stratification and prognostic medicine. Observational studies have reported an inverse association between physical activity and basal cardiac troponin levels. However, causality has never been demonstrated. This study investigated whether basal cardiac troponin concentrations are receptive to lifestyle interventions such as exercise training. Basal high-sensitive cardiac troponin T ( cTnT ) and I ( cTnI ) were monitored in two resistance-type exercise training programs ( 12-week ( study 1 ) and 24-week ( study 2 ) ) in older adults ( ≥65 years ). In addition, a retrospective analysis for high sensitive troponin I in a 24-week exercise controlled trial in ( pre )frail older adults was performed ( study 3 ). In total, 91 subjects were included in the final data analyses. There were no significant changes in cardiac troponin levels over time in study 1 and 2 ( study 1: cTnT −0.13 ( −0.33–+0.08 ) ng/L/12-weeks, cTnI −0.10 ( −0.33–+0.12 ) ng/L/12-weeks; study 2: cTnT −1.99 ( −4.79–+0.81 ) ng/L/24-weeks, cTnI −1.59 ( −5.70–+2.51 ) ng/L/24-weeks ). Neither was there a significant interaction between training and the course of cardiac troponin in study 3 ( p = 0.27 ). In conclusion, this study provides no evidence that prolonged resistance-type exercise training can modulate basal cardiac troponin levels

Combining high sensitivity cardiac troponin I and cardiac troponin T in the early diagnosis of acute myocardial infarction

-Combining two signals of cardiomyocyte injury, cardiac troponin I (cTnI) and T (cTnT), might overcome some individual pathophysiological and analytical limitations and thereby increase diagnostic accuracy for acute myocardial infarction (AMI) with a single blood draw. We aimed to evaluate the diagnostic performance of combinations of high sensitivity (hs) cTnI and hs-cTnT for the early diagnosis of AMI. -The diagnostic performance of combining hs-cTnI (Architect, Abbott) and hs-cTnT (Elecsys, Roche) concentrations (sum, product, ratio and a combination algorithm) obtained at the time of presentation was evaluated in a large multicenter diagnostic study of patients with suspected AMI. The optimal rule out and rule in thresholds were externally validated in a second large multicenter diagnostic study. The proportion of patients eligible for early rule out was compared with the ESC 0/1 and 0/3 hour algorithms. -Combining hs-cTnI and hs-cTnT concentrations did not consistently increase overall diagnostic accuracy as compared with the individual isoforms. However, the combination improved the proportion of patients meeting criteria for very early rule-out. With the ESC 2015 guideline recommended algorithms and cut-offs, the proportion meeting rule out criteria after the baseline blood sampling was limited (6-24%) and assay dependent. Application of optimized cut-off values using the sum (9 ng/L) and product (18 ng2/L2) of hs-cTnI and hs-cTnT concentrations led to an increase in the proportion ruled-out after a single blood draw to 34-41% in the original (sum: negative predictive value (NPV) 100% (95%CI: 99.5-100%); product: NPV 100% (95%CI: 99.5-100%) and in the validation cohort (sum: NPV 99.6% (95%CI: 99.0-99.9%); product: NPV 99.4% (95%CI: 98.8-99.8%). The use of a combination algorithm (hs-cTn

Determination of Faecal Fat by Near-Infrared Spectroscopy

Peer Reviewe

Contemporary oxygenator design relative to hemolysis

Hemolysis is a well-known phenomenon during cardiovascular surgery and generally attributed to cardiopulmonary bypass, particularly when using high-resistant oxygenators. This study aimed at investigating whether transoxygenator pressure drop can be considered an independent factor of hemolysis. Additionally, intraoxygenator blood distribution and shear stress were assessed. A low-resistant (LR, n = 3), a moderate-resistant (MR, n = 3), and a high-resistant (HR, n = 3) clinically used membrane oxygenator were tested in vitro using a roller pump and freshly drawn heparinized porcine blood. Flow rates were set to 2 and 4 L/min and maximum flow compliant to the oxygenator type for 1 hour each. As a control, the oxygenator was excluded from the system. Blood samples were taken every 30 minutes for plasma-free hemoglobin assay and transoxygenator pressure was measured inline. Intraoxygenator blood distribution was assessed using an ultrasound dilution technique. Despite the relatively broad spectrum of pressure drop and resultant transoxygenator pressure drops (LR: 14-41 mmHg, MR: 29-115 mmHg, HR: 77-284 mmHg, respectively), no significant association (R2 = .074, p = .22) was found with the normalized index of hemolysis. The shear stress of each oxygenator at maximum flow rate amounted to 3.0 N/m2 (LR), 5.7 N/m2 (MR), and 8.4 N/m2 (HR), respectively. Analysis of blood flow distribution curves (kurtosis and skewness) revealed intraoxygenator blood flow distribution to become more homogeneous when blood flow rates increased. Contemporary oxygenators were shown not to be a predominant factor for red blood cell damage