hs-cTnT Concentrations Research Articles

Exercise-induced cardiac troponins in long-distance walkers: a preliminary observation.

Abstract Background Elevated concentrations of cardiac troponin (cTnT and cTnI), the preferred biomarker to diagnose myocardial infarction, can be detected in other (cardiac) conditions and even post-exercise. Whether these exercise-induced elevations reflect a (patho)physiological process, as well as their clinical implications, is unknown. In this preliminary study, pre- and post-exercise high-sensitivity cTn (hs-cTnT and hs-cTnI) concentrations were investigated in long-distance walkers. Purpose Gain insight of elevated cTnT and cTnI concentrations post-exercise in long-distance walkers. Methods From 478 participants, walking 30-50 km on the first day of the 4Daagse 2023, blood-samples were collected pre- and <6h post-exercise. In addition, health and exercise questionnaires were conducted. Hs-cTnT (Roche) and hs-cTnI (Abbott) concentrations were determined and the unisex, female and male Upper Reference Limit (URL) were according to package inserts (Roche: 14 ng/L, 9 ng/L, 16 ng/L, Abbott: 26 ng/L, 16 ng/L, 34 ng/L). Results Participants (51% female) were 57±7.6 years (mean±SD). At baseline, median [IQR] hs-cTnT and hs-cTnI were 5.9 [4.5-8.0] and 1.7 [1.1-2.9] ng/L, which increased significantly post-exercise to 8.7 [6.4-12.4] ng/L (P<0.001) and 5.2 [3.1-9.5] ng/L (P<0.001). Pre-exercise, the unisex-URL for hs-cTnT was exceeded by 4.4% walkers and for sex-specific URLs, this resulted in 6.6% females and 3.8% males. For hs-cTnI, the unisex-URL was exceeded by 0.6%, as for sex-specific URLs, 0.8% females and 1.3 % males surpassed. Post-exercise, hs-cTnT URLs were exceeded by 18.2%, 35.1%, 16.5% and as for hs-cTnI post-exercise, 7.3%, 11.6%, 3.8% for unisex, female and male. Alternatively, the absolute median delta difference was 2.4 [0.9-4.6] ng/L for hs-cTnT and 3.0 [1.6-5.7] ng/L hs-cTnI. Conclusion Post-exercise long-distance walkers had significantly increased hs-cTnT and hs-cTnI concentrations, in particular in women when using sex-specific cutoffs. In order to understand clinical implications of these findings, status of cardiac vascular diseases, risk-factors and exercise characteristics will be analyzed in the future.

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

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

Diagnosis of acute myocardial infarction in patients with renal failure using high-sensitivity cardiac troponin T

Abstract Background Diagnosing myocardial infarction (MI) in patients with chronic kidney disease (CKD) is difficult as these patients often have elevated baseline high-sensitivity cardiac troponin T (hs-cTnT) concentrations. Methods Observational U.S. cohort study of emergency department (ED) patients undergoing hs-cTnT measurement. Cases with >1 hs-cTnT increase >99th percentile were adjudicated following the Fourth Universal Definition of MI. Diagnostic performance of baseline and serial 2- and 6-hour hs-cTnT thresholds for ruling-in acute MI was compared between those without and with CKD (eGFR <60 ml/min/1.73m2). Results The study cohort included 1992 patients, amongst whom 501 (25%) had CKD. There were 701 (82%) patients with myocardial injury, 64 (7.5%) with type 1, and 91 (11%) with type 2 MI. In CKD patients with baseline hs-cTnT thresholds of >52, >100, >200 or >300 ng/L, PPVs for acute MI were 37% [95% CI 28-46], 53% (95% CI 39-67), 73% (95% CI 50-89) and 80% (95% CI 44-98), and in those without CKD, 64% (95% CI 50-77), 69% (95% CI 49-85), 59% (95% CI 33-82) and 54% (95% CI 25-81). In CKD patients with a 2-hour hs-cTnT delta of >10, >20 or >30 ng/L, the corresponding PPVs were 65% (95% CI 50-78), 86% (95% CI 68-96) and 88% (95% CI 68-97), and in those without CKD, 65% (95% CI 51-78), 73% (95% CI 57-86) and 75% (95% CI 58-88) (Figure). Conclusion Diagnostic performance of standard baseline and serial 2-hour hs-cTnT thresholds to rule-in MI is suboptimal in patients with CKD. It significantly improves when using higher baseline thresholds and delta values.

Acute kidney injury in relation to high-sensitivity cardiac troponin T levels in the emergency department

Abstract Background The clinical implications of high-sensitivity cardiac troponin T (hs-cTnT) measurements in all-comers with AKI in the emergency department (ED) is largely unknown. Purpose To investigate the prevalence of myocardial injury, associations between serum-creatinine concentrations (SCC) and hs-cTnT kinetics, and the accuracy of established hs-cTnT-based myocardial infarction (MI) risk stratification algorithm criteria in patients with AKI. Methods This observational cohort study was based on patient visits to 7 EDs in Sweden from December 9, 2010 to August 31, 2017. All visits by patients ≥18 years fulfilling criteria for AKI with ≥1 hs-cTnT measurement and the exposure was dynamic change in SCC (ΔSCC) during the visits. Linear mixed models were used to estimate linear predictors of kinetic change in hs-cTnT (Δhs-cTnT). Logistic regression models were applied to calculate odds ratios (ORs) for Δhs-cTnT indicative of acute myocardial injury (Δhs-cTnT >20% and elevated hs-cTnT) in relation to ΔSCC among patients without MI, and to assess the diagnostic performance of hs-cTnT for MI in a subgroup of patients presenting with chest pain. Results A total of 15,211 visits by patients with AKI were included, of whom 1174 (8%) had an MI. Four of five (81%) patients without MI had myocardial injury (hs-cTnT >14 ng/l), and almost one of three (31%) had acute myocardial injury. These entities were common in both cardiac and non-cardiac conditions. The Δhs-cTnT in non-MI patients was 1.8-fold (β: 1.78, 95% CI: 1.62-1.96) in the highest quartile of ΔSCC and was paralleled by a 2-fold risk of acute myocardial injury (OR: 2.32, 95% CI: 2.08-2.59), compared with the lowest ΔSCC quartile. Using a 0 h hs-cTnT cut-off ≥52 ng/l assigned 627 (26%) patients to a high-risk group in whom the specificity and positive predictive value (PPV) for MI was low (78.5% (95% CI: 76.7-80.2) and 27.6% (95% CI: 24.1-31.3), respectively). Conclusions Hs-cTnT concentrations indicative of acute myocardial injury are frequently observed among all-comers with AKI in the ED and are associated with dynamic changes in SCC. These observations are accompanied by poor performance of recommended hs-cTnT-based algorithms for MI risk stratification in patients with chest pain.

False-positive cardiac troponin I values in healthy athletes post COVID-19 Infection: concerning insights from a prospective cohort study

Abstract Background Cardiac troponin I and T (cTnI, cTnT) are cardiac-specific biomarkers that detect and quantify cardiomyocyte injury. In patients with symptoms possibly indicating acute myocardial infarction (AMI), detection of elevated cTnT or cTnI concentrations usually mandates invasive coronary angiography. Accordingly, false-positive cTnT or cTnI concentrations could have detrimental consequences. Unfortunately, little is known about the prevalence and triggers of false-positive cTnI concentrations. Based on two index cases seen by one of us, we hypothesized that false-positive cTnI values may be common after COVID-19 infection and that macrotroponin, a complex formed between endogenous cTn autoantibodies and circulating cTn, may be the underlying cause. Purpose We aimed to test these hypotheses in a prospective cohort study. Methods We prospectively investigated professional athletes coming to the mandatory return to sports investigation at least 10 days after COVID-19 infection between 2022 and 2023 in an observational study. The presence of false-positive cTnI was centrally adjudicated in individuals that had elevated cTnI concentrations with one (or two) high-sensitivity cTnI assays, but normal high-sensitivity cardiac troponin T concentrations and normal electrocardiography (ECG), normal echocardiography, and normal cardiac magnetic resonance imaging (CMR). Divergences in hs-cTn concentrations were investigated using sex-specific upper limits of normal (ULN) of 4 different assays (hs-cTnI: Alinity/Abbott Diagnostic, hs-cTnI: Atellica/Siemens Healthineers, hs-cTnI: Access Beckman Coulter; hs-cTnT: Cobas/Roche Diagnostics). Athletes were instructed to cease training 48 hours before blood testing. Athletes with divergent hs-cTn assay results underwent further analysis for macrotroponin using sucrose gradient ultracentrifugation. Results Among 35 enrolled athletes (median age 24 years, 19 women and 16 men), 18 athletes had normal hs-cTn concentrations with all four hs-cTnT/I assays. In 17 athletes (48.6%), hs-cTn concentration was increased in at least one assay above the ULN, mostly one hs-cTnI method (hs-cTnI, Alinity) with normal concentrations of the other assays and normal cardiac imaging results. In contrast, two athletes had elevations in all hs-cTnI/T assays. Sucrose gradient ultracentrifugation provided evidence of macrotroponin in 15 of the 17 athletes (88%). Conclusions False-positive cTnI values are common after COVID-19 infection and should be considered in the differential diagnosis. Assay interference by macrotroponin seems to be the underlying mechanisms in most individuals. Documentation of normal hs-cTnT concentrations helps in the early detection of false-positive cTnI values.

A-023 Early Concentrations of Long Cardiac Troponin T Forms in Myocardial Infarction Patients

Abstract Background Long forms of cardiac troponin T (cTnT) represent a new promising biomarker for more specific diagnostics of myocardial infarction (MI). We studied for the first time the concentrations of long cTnT forms in a panel including very early samples of type 1 MI patients. Methods Heparin plasma samples were drawn from 94 type 1 MI patients 0.4-24 h after the symptom onset and analyzed with Roche hs-cTnT assay and with our novel highly sensitive upconversion luminescence-based long cTnT immunoassay. The long cTnT assay detects all cTnT forms not cleaved at the major C-terminal cleavage site at cTnT amino acid residues 189-220 while the Roche hs-cTnT assay detects all short and long cTnT forms containing the stable central part of cTnT. Troponin ratio, reflecting the fraction of the long cTnT forms, was calculated by dividing the long cTnT result by the Roche hs-cTnT result. Results The long cTnT and Roche hs-cTnT concentrations varied highly (median 107 [25th-75th percentile 20-1195] ng/L and 277 [62-1422] ng/L, respectively) and correlated significantly with each other (r=0.881, p<0.001). Neither had a significant correlation with time from symptom onset. Troponin ratio was highly variable especially at the first hours, but there was a clear decreasing trend in variability later (Figure). Troponin ratio showed significant negative correlation with time (r=-0.284, p=0.005) and the correlation became stronger with longer delays between symptom onset and sampling (6-24 h, r=-0.422, p<0.001). Conclusions A significant portion of circulating cTnT is in long forms in type 1 acute MI patients at early stage. The fraction of long cTnT forms is highly variable in the very early hours after MI, but shows a clear decreasing trend after 6 hours from the pain onset.

Luteinizing hormone is independently associated with high-sensitive cardiac troponin T elevation in postmenopausal T2DM patients: A cross-sectional study.

It is known that the risk of ischemic heart disease increases in patients with type 2 diabetes mellitus (T2DM). For female patients, the incidence of heart disease can be even greater after menopause, accompanied by dramatic changes in sex hormones. We investigated the correlations between sex hormones and markers of ischemic heart diseases in postmenopausal females with T2DM patients. This cross-sectional study collected data from 324 hospitalized postmenopausal females with T2DM. Multiple linear regression analyses were conducted to determine the correlations between sex hormones and cardiac markers including high-sensitive cardiac troponin T (hs-cTnT) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels. Multiple linear regression analyses revealed that luteinizing hormone (LH) was positively and independently associated with hs-cTnT concentrations in postmenopausal females with T2DM (β = 0.189, p = 0.002). Postmenopausal females with T2DM and subclinical myocardial injury had higher LH levels than those without subclinical myocardial injury (29.67 vs. 25.08 mIU/mL, p < 0.001). A multivariate logistic regression analysis confirmed an independent and significant association between elevated LH and subclinical myocardial injury in postmenopausal females with T2DM (adjusted odds ratio [OR] = 1.077, 95% confidence interval [CI], 1.033-1.124; p < 0.001). As another gonadotropin, the follicle-stimulating hormone did not show independent correlations with hs-cTnT or NT-proBNP (p > 0.05). Neither estrogen nor testosterone was correlated with cardiac markers. Elevated LH levels were positively and independently associated with increased hs-cTnT levels in postmenopausal women with T2DM. Our findings suggest that LH could serve as a potential marker for assessing the risk of subclinical myocardial injury in postmenopausal females with T2DM.

NT-proBNP and Cardiac Troponin I, but Not Cardiac Troponin T, Are Associated With 7-Year Changes in Cardiac Structure and Function in Older Adults: The ARIC Study.

Higher circulating concentrations of NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI) are associated with left ventricular remodeling and with incident heart failure. The associations of these cardiac biomarkers with changes in cardiac structure and function over time are uncharacterized. Among 2006 participants in the ARIC prospective cohort study (Atherosclerosis Risk in Communities) who were free of overt cardiovascular disease and underwent echocardiography at study visits 5 (2011- 2013) and 7 (2018-2019), we assessed the associations of NT-proBNP, hs-cTnT, and hs-cTnI concentrations at visit 5 with changes in left ventricular structure and function between visits 5 and 7 (≈7-year change) using multivariable linear regression with the biomarkers modeled as restricted cubic splines. Models were adjusted for age, sex, race, body mass index, smoking, diabetes, hypertension, and renal function at visit 5; blood pressure and heart rate at both visits; and the baseline value of the echocardiographic parameter of interest. Mean±SD age was 74±4 years at visit 5; 61% were women; and 23% were Black adults. Median (25th-75th percentile) concentrations at visit 5 of NT-proBNP, hs-cTnT, and hs-cTnI were 87 ng/L (50-157 ng/L), 9 ng/L (6-12 ng/L), and 2.6 ng/L (1.9-3.9 ng/L). In adjusted models, elevated baseline concentrations of NT-proBNP and hs-cTnI were significantly associated with 7-year decline in left ventricular systolic function (ejection fraction, longitudinal and circumferential strain) and worsening diastolic indices. In contrast, elevated baseline concentrations of hs-cTnT were not significantly associated with 7-year changes in cardiac structure, systolic function, or diastolic function (all P>0.05). Higher concentrations of NT-proBNP and hs-cTnI, but not hs-cTnT, were associated with greater declines in left ventricular function over ≈7 years in late life independently of traditional cardiovascular risk factors.AQ.

Monitoring of myocardial injury by serial measurements of QRS area and T area: The MaastrICCht cohort.

Manually derived electrocardiographic (ECG) parameters were not associated with mortality in mechanically ventilated COVID-19 patients in earlier studies, while increased high-sensitivity cardiac troponin-T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were. To provide evidence for vectorcardiography (VCG) measures as potential cardiac monitoring tool, we investigated VCG trajectories during critical illness. All mechanically ventilated COVID-19 patients were included in the Maastricht Intensive Care Covid Cohort between March 2020 and October 2021. Serum hs-cTnT and NT-proBNP concentrations were measured daily. Conversion of daily 12-lead ECGs to VCGs by a MATLAB-based script provided QRS area, T area, maximal QRS amplitude, and QRS duration. Linear mixed-effect models investigated trajectories in serum and VCG markers over time between non-survivors and survivors, adjusted for confounders. In 322 patients, 5461 hs-cTnT, 5435 NT-proBNP concentrations and 3280 ECGs and VCGs were analyzed. Non-survivors had higher hs-cTnT concentrations at intubation and both hs-cTnT and NT-proBNP significantly increased compared with survivors. In non-survivors, the following VCG parameters decreased more when compared to survivors: QRS area (-0.27 (95% CI) (-0.37 to -0.16, p < .01) μVs per day), T area (-0.39 (-0.62 to -0.16, p < .01) μVs per day), and maximal QRS amplitude (-0.01 (-0.01 to -0.01, p < .01) mV per day). QRS duration did not differ. VCG-derived QRS area and T area decreased in non-survivors compared with survivors, suggesting that an increase in myocardial damage and tissue loss play a role in the course of critical illness and may drive mortality. These VCG markers may be used to monitor critically ill patients.

Kidney function-specific cut-off values of high-sensitivity cardiac troponin T for the diagnosis of acute myocardial infarction.

The diagnosis of acute myocardial infarction (AMI) using high-sensitivity cardiac troponin T (hs-cTnT) remains challenging in patients with kidney dysfunction. In this large, multicenter cohort study, a total of 20912 adults who underwent coronary angiography were included. Kidney function-specific cut-off values of hs-cTnT were determined to improve the specificity without sacrificing sensitivity, as compared with that using traditional cut-off value (14ng/L) in the normal kidney function group. The diagnostic accuracy of the novel cut-off values was validated in an independent validation cohort. In the derivation cohort (n=12900), 3247 patients had an estimated glomerular filtration rate (eGFR) <60mL/min/1.73 m2. Even in the absence of AMI, 50.2% of participants with eGFR <60mL/min/1.73 m2 had a hs-cTnT concentration ≥14ng/L. Using 14ng/L as the threshold of hs-cTnT for diagnosing AMI led to a significantly reduced specificity and positive predictive value in patients with kidney dysfunction, as compared with that in patients with normal kidney function. The kidney function-specific cut-off values were determined as 14, 18 and 48ng/L for patients with eGFR >60, 60-30 and <30mL/min/1.73 m2, respectively. Using the novel cut-off values, the specificities for diagnosing AMI in participants with different levels of kidney dysfunction were remarkably improved (from 9.1%-52.7% to 52.8-63.0%), without compromising sensitivity (96.6%-97.9%). Similar improvement of diagnostic accuracy was observed in the validation cohort (n=8012). The kidney function-specific cut-off values of hs-cTnT may help clinicians to accurately diagnose AMI in patients with kidney dysfunction and avoid the potential overtreatment in practice.

Cardioprotective Efficacy of Sevoflurane in Patients With Rheumatic Heart Disease Undergoing Heart Valve Surgery Under Cardiopulmonary Bypass.

In this study, we investigated whether cardioprotective properties of sevoflurane were expressed in patients with rheumatic heart disease undergoing heart valve surgery under cardiopulmonary bypass (CPB). Fifty patients with rheumatic heart disease undergoing heart valve surgery under CPB were randomly assigned to receive total anesthesia with sevoflurane or propofol during surgery. Except for this, anesthetic and surgical management was the same in all patients. The primary outcomes were postoperative high-sensitive cardiac troponin T (hs-cTnT) and creatine kinase-myocardial band (CK-MB) release. The secondary outcomes were hemodynamic events and short-term clinical outcomes (within 30 days after surgery). The plasma concentrations of hs-cTnT at 24-hour and CK-MB from 6-hour to 48-hour in the sevoflurane group were lower than those in the control group (the propofol group). After aortic unclamping, heartbeat recovery was faster and the rate of sinus rhythm was higher in the sevoflurane group than in the control group. Moreover, a lower proportion of pacemaker use and the need for intraoperative and postoperative inotropes were also found in the sevoflurane group. Nevertheless, there were no differences between the two groups regarding short-term clinical outcomes (durations of mechanical ventilation, intensive care unit stay, hospital stay, morbidity, and mortality rates). Sevoflurane administered during the entire anesthetic procedure had a myocardial protective effect with less evidence of myocardial damage in the first 48-hour postoperatively but short-term clinical outcomes were not significantly different when compared with the control group in patients with rheumatic heart disease undergoing heart valve surgery under CPB.

Acute Kidney Injury and High-Sensitivity Cardiac Troponin T Levels in the Emergency Department

The clinical implications of high-sensitivity cardiac troponin T (hs-cTnT) measurements in patients with acute kidney injury (AKI) in the emergency department (ED) are largely unknown. To investigate associations between serum creatinine (SCr) concentrations and hs-cTnT kinetics, as well as the clinical accuracy of hs-cTnT for myocardial infarction (MI) in patients with AKI. This retrospective cohort study included 15 111 patient visits to 7 EDs in Sweden from December 9, 2010, to August 31, 2017, by patients 18 years or older fulfilling AKI criteria with 2 or more SCr measurements and 1 or more hs-cTnT measurement. Statistical analysis was performed from October 2, 2022, to September 28, 2023. Dynamic change in SCr during the ED visits. Linear mixed-effects models were used to estimate the log-linear regression of kinetic change in hs-cTnT. Logistic regression models were applied to calculate odds ratios (ORs) for change in hs-cTnT indicating acute myocardial injury (Δhs-cTnT >20% and elevated hs-cTnT >14 ng/L) in association with change in SCr, and to assess the diagnostic performance of hs-cTnT for MI in patients with chest pain. There was a total of 15 211 visits by 13 638 patients (median age, 74 years [IQR, 64-83 years]; 8709 men [57%]), of whom 1174 (8%) had an MI. Overall, 11 353 of patients at 14 037 visits without an MI diagnosis (81%) had myocardial injury, and 4396 patients at 14 037 visits (31%) had acute myocardial injury. The change in hs-cTnT among patients without MI was 1.8-fold higher in the highest vs the lowest change in SCr quartile (64.7% [95% CI, 58.4%-71.5%] vs 36.3% [95% CI, 32.4%-40.7%]; exponentiated β coefficient, 1.78 [95% CI, 1.62-1.96]). Patients in the former group were twice as likely to have acute myocardial injury (39% [1378 of 3516 visits] vs 23% [817 of 3507 visits]; adjusted OR, 2.32 [95% CI, 2.08-2.59]). Using a 0 hours hs-cTnT cutoff value of 52 ng/L or higher assigned 627 of 2388 patients (26%) with chest pain to a high-risk group in whom the specificity and positive predictive value for MI was low (78.5% [95% CI, 76.7%-80.2&] and 27.6% [95% CI, 24.1%-31.3%], respectively). This cohort study of patients in the ED suggests that dynamic change in SCr among patients with AKI was associated with hs-cTnT concentrations indicative of acute myocardial injury. These observations were accompanied by poor performance of recommended hs-cTnT-based algorithms for MI risk stratification.

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

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

Interpretation of elevated baseline concentrations and serial changes of high-sensitivity cardiac troponin T in confirmed muscular dystrophies.

Concentrations of high-sensitivity cardiac troponin T (hs-cTnT) are frequently elevated in stable patients with confirmed muscle dystrophies. However, sparse information is available on the interpretation of serial concentration changes. Hs-cTnT was collected in 35 stable outpatients with confirmed skeletal muscle dystrophies at 0 and 1h and after 6-12months during scheduled outpatient visits. We simulated the effectiveness of the European Society of Cardiology (ESC) 0/1h algorithm and assessed biological variation at 6-12months using two established methods: reference change value (RCV) and minimal important difference (MID). Median baseline hs-cTnT concentrations were 34.4ng/L [inter-quartile range (IQR): 17.5-46.2], and values > 99th percentile upper limit of normal were present in 34 of 35 patients. All patients were stable without cardiovascular adverse events during a follow-up of 6.6months (IQR: 6-7). Median concentration change was 1.9ng/L (IQR: 0.7-3.2) and 0.8ng/L (IQR: 0-7.0) at 60min and 6-9months, respectively. Applying the criteria of the ESC 0/1h algorithm for triage of suspected acute coronary syndrome (ACS) showed poor overall effectiveness of baseline hs-cTnT values. No patient would qualify for rule-out based on hs-cTnT less than the limit of detection, whereas five cases would qualify for rule-in based on hs-cTnT≥52ng/L. Biological variabilities at 6-12months per MID and RCV were 1.2ng/L [95% confidence interval (CI): 0.7-2.1] and 28.6% (95% CI: 27.9-29.6), respectively. A total of 8 (22.9%) and 25 (71.4%) cases exceeded the biological variation range, suggesting some additional myocardial damage. The high prevalence of elevated hs-cTnT could negatively impact the effectiveness of rule-out and rule-in strategies based on a single hs-cTnT value. Knowledge of the physiological and biological variation of hs-cTnT after 6-12months is helpful to detect the progression of cardiac involvement or to search for cardiac complications including but not limited to arrhythmias that may trigger acute or chronic myocardial damage.

High-sensitive troponin T, suPAR and Beta-2-microglobulin changes in concentration during hemodialysis

Hemodialysis (HD) patients are at high risk of cardiovascular disease and death. Reliable biomarkers for risk stratification and detection of acute myocardial infarction (AMI) are therefore pivotal. Cardiac troponins (cTn) are the preferred biomarkers for AMI. It remains unclear, if cTn concentrations changes as a consequence of HD treatment itself during dialysis. In this study, cTn was compared with soluble urokinase plasminogen activator receptor (suPAR) and Beta-2-microglobulin (B2M). We performed a prospective study including 17 HD patients measuring high-sensitive cardiac troponin t (hs-cTnT), suPAR and B2M before and after a dialysis session and verified the results in a random subgroup of eight patients from the group by repeating their measurements before and after a dialysis session 15 weeks later. Biomarker concentrations after dialysis were adjusted according to hemodilution or concentration according to the hemoglobin concentration. The average hs-cTnT concentration decreased significantly by −9.9% after dialysis (95% CI: −13.6% to −6.2%). The average (paired) difference were − 6.7 ng/L (p = 0.0104) after dialysis comparing 25 HD treatment occasions. SuPAR was not significantly influenced by dialysis. B2M decreased by −58% after HD as an expected result from the molecular size of the biomarker. The hs-cTnT in average decreased by −9.9% after dialysis. This is a diagnostic challenge since the current guidelines suggest a 20% change in hs-cTnT in patients with acute myocardial infarction. Larger prospective studies investigating the different factors influencing hs-cTnT after HD are warranted. Adjusting biomarker concentrations according to hemodilution or concentration using the hemoglobin concentration, should be considered in future studies to determine more exact changes in concentrations of cTnT and other relevant biomarkers.

Diagnosis of acute myocardial infarction in patients with renal failure using high-sensitivity cardiac troponin T.

Diagnosing myocardial infarction (MI) in patients with chronic kidney disease (CKD) is difficult as they often have increased high-sensitivity cardiac troponin T (hs-cTnT) concentrations. Observational US cohort study of emergency department patients undergoing hs-cTnT measurement. Cases with ≥1 hs-cTnT increase > 99th percentile were adjudicated following the Fourth Universal Definition of MI. Diagnostic performance of baseline and serial 2 h hs-cTnT thresholds for ruling-in acute MI was compared between those without and with CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m2). The study cohort included 1992 patients, amongst whom 501 (25%) had CKD. There were 75 (15%) and 350 (70%) patients with CKD and 80 (5%) and 351 (24%) without CKD who had acute MI and myocardial injury. In CKD patients with baseline hs-cTnT thresholds of ≥52, >100, >200, or >300 ng/L, positive predictive values (PPVs) for MI were 36% (95% CI 28-45), 53% (95% CI 39-67), 73% (95% CI 50-89), and 80% (95% CI 44-98), and in those without CKD, 61% (95% CI 47-73), 69% (95% CI 49-85), 59% (95% CI 33-82), and 54% (95% CI 25-81). In CKD patients with a 2 h hs-cTnT delta of ≥10, >20, or >30 ng/L, PPVs were 66% (95% CI 51-79), 86% (95% CI 68-96), and 88% (95% CI 68-97), and in those without CKD, 64% (95% CI 50-76), 73% (95% CI 57-86), and 75% (95% CI 58-88). Diagnostic performance of standard baseline and serial 2 h hs-cTnT thresholds to rule-in MI is suboptimal in CKD patients. It significantly improves when using higher baseline thresholds and delta values.

The role of functional vitamin D deficiency and low vitamin D reservoirs in relation to cardiovascular health and mortality.

The role of vitamin D deficiency in cardiovascular disease (CVD) is controversial. Inherent biological and analytical limitations compromise the specificity of widely used 25-hydroxyvitamin D [25(OH)D] cut-offs. Simultaneous determination of 25(OH)D and 24,25-dihydroxyvitamin D [24,25(OH)2D] permits a functional assessment of vitamin D metabolism. The present study compared the associations of functional vitamin D deficiency and low vitamin D reservoirs with CVD mortality and CVD burden. 25(OH)D, 24,25(OH)2D, the degree of coronary obstruction on angiography, high-sensitive cardiac troponin T (hs-cTnT), N-terminal brain natriuretic peptide (NT-proBNP), and 10-year CVD mortality were obtained from 2,456 participants of the LURIC (Ludwigshafen Risk and Cardiovascular Health) study. Neither low 25(OH)D concentrations nor functional vitamin D deficiency were associated with the number of atherosclerotic coronary arteries or the degree of coronary obstruction. Over a median follow-up of 9.9 years, 454 participants died (23.6 %) due to CVD. CVD mortality was doubled in individuals with 25(OH)D concentrations below the widely used cut-off for deficiency of <50 nmol/L [20 ng/mL] (21.6 vs. 11.5 %). In individuals with and without functional vitamin D deficiency, CVD mortality was 25.0 and 16.7 %, respectively. NT-proBNP and heart failure prevalence were also higher in vitamin D deficient individuals. Vitamin D deficient individuals have markedly higher CVD mortality, but only marginally higher hs-cTnT concentrations. A higher prevalence of heart failure and higher NT-proBNP concentrations suggest a link between vitamin D deficiency and cardiac function. The traditional and metabolic assessment of vitamin D status showed comparable associations for the different parameters of cardiac health.

Long-term prognosis of low high-sensitivity cardiac troponin T in the emergency department compared with the general population

BackgroundLong-term prognosis associated with low–high-sensitivity cardiac troponin T (hs-cTnT) concentrations in patients with chest pain is unknown. We investigated these prognostic implications compared with the general population.MethodsAll first visits to...

Cardiovascular medications, high-sensitivity cardiac troponin T concentrations, and long-term outcome in non-ST segment elevation acute coronary syndrome.

Cardiac troponin plays an essential role in the management of non-ST segment elevation acute coronary syndrome (NSTE-ACS). However, it is not clear whether troponin concentrations provide guidance regarding the initiation of prognostically beneficial cardiovascular medications [i.e. betablockers, renin-angiotensin-aldosterone system (RAAS) inhibitors, and statins] in NSTE-ACS. Registry-based study investigating three NSTE-ACS cohorts (n = 43 075, 40 162, and 46 698) with elevated high-sensitivity cardiac troponin concentrations >14 ng/L. Cox proportional regression models with the addition of interaction terms were used to analyse the interrelations of high-sensitivity cardiac troponin T (hs-cTnT) concentrations, new initiated medications with the respective three drug classes, and long-term risk of all-cause mortality and major adverse events (MAE). Betablockers were associated with risk reductions of 8 and 5% regarding all-cause mortality and MAE, respectively. There was no evidence of an interaction with hs-cTnT concentrations. RAAS inhibitors were associated with 13 and 8% risk reductions, respectively, with a weak interaction between hs-cTnT and MAE (Pinteraction = 0.016). However, no increasing prognostic benefit was noted at hs-cTnT concentrations >100 ng/L. Statins were associated with 38 and 32% risk reductions, respectively, with prognostic benefit across the entire range of hs-cTnT concentrations, and with a weak interaction regarding MAE (Pinteraction = 0.011). Cardiovascular medications provide different prognostic benefit in patients with NSTE-ACS with elevated hs-cTnT, and there was some evidence of greater treatment effects regarding MAE along with higher hs-cTnT concentrations. However, hs-cTnT appears only to have limited value overall for customizing such treatments.

Differences in Cardiac Troponin T Composition in Myocardial Infarction and End-Stage Renal Disease Patients: A Blood Tube Effect?

Cardiac troponin T (cTnT) is key in diagnosing myocardial infarction (MI) but is also elevated in end-stage renal disease (ESRD) patients. Specific larger cTnT proteoforms were identified for the acute phase of MI, while in serum of ESRD patients solely small cTnT fragments were found. However, others allocated this to a pre-analytic effect due to abundant thrombin generation in serum. Therefore, we investigated the effect of various anticoagulation methods on cTnT composition and concentration and compared the cTnT composition of MI and ESRD patients. The agreement of cTnT concentrations between simultaneously collected serum, lithium-heparin (LH) plasma, and ethylenediaminetetraacetic acid (EDTA) plasma was studied using the high-sensitivity (hs-)cTnT immunoassay. cTnT proteoform composition was investigated in a standardized time-dependent manner through spike experiments and in simultaneously collected blood matrixes of MI and ESRD patients. Excellent hs-cTnT concentration agreements were observed across all blood matrixes (slopes > 0.98; 95% CI, 0.96-1.04). Time-dependent degradation (40 kDa intact:29 kDa fragment:15 to 18 kDa fragments) was found in LH plasma and EDTA plasma, and serum in ratios (%) of 90:10:0, 0:5:95, and 0:0:100, respectively (48 h after blood collection). Moreover, gel filtration chromatography (GFC) profiles illustrated mainly larger cTnT proteoforms in MI patients, while in ESRD patients mainly 15 to 18 kDa fragments were found for all matrices. The extent of cTnT degradation in vitro is dependent on the (anti)coagulation method, without impacting hs-cTnT concentrations. Furthermore, mainly larger cTnT proteoforms were present in MI patients, while in ESRD patients mainly small 15 to 18 kDa cTnT fragments were found. These insights are essential when developing a novel hs-cTnT assay targeting larger cTnT proteoforms.