Measurement Of Cardiac Troponin Research Articles

Prognostic Value of Cardiovascular Biomarkers in the Population

Identification of individuals at high risk for atherosclerotic cardiovascular disease within the population is important to inform primary prevention strategies. To evaluate the prognostic value of routinely available cardiovascular biomarkers when added to established risk factors. Individual-level analysis including data on cardiovascular biomarkers from 28 general population-based cohorts from 12 countries and 4 continents with assessments by participant age. The median follow-up was 11.8 years. Measurement of high-sensitivity cardiac troponin I, high-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide, B-type natriuretic peptide, or high-sensitivity C-reactive protein. The primary outcome was incident atherosclerotic cardiovascular disease, which included all fatal and nonfatal events. The secondary outcomes were all-cause mortality, heart failure, ischemic stroke, and myocardial infarction. Subdistribution hazard ratios (HRs) for the association of biomarkers and outcomes were calculated after adjustment for established risk factors. The additional predictive value of the biomarkers was assessed using the C statistic and reclassification analyses. The analyses included 164 054 individuals (median age, 53.1 years [IQR, 42.7-62.9 years] and 52.4% were women). There were 17 211 incident atherosclerotic cardiovascular disease events. All biomarkers were significantly associated with incident atherosclerotic cardiovascular disease (subdistribution HR per 1-SD change, 1.13 [95% CI, 1.11-1.16] for high-sensitivity cardiac troponin I; 1.18 [95% CI, 1.12-1.23] for high-sensitivity cardiac troponin T; 1.21 [95% CI, 1.18-1.24] for N-terminal pro-B-type natriuretic peptide; 1.14 [95% CI, 1.08-1.22] for B-type natriuretic peptide; and 1.14 [95% CI, 1.12-1.16] for high-sensitivity C-reactive protein) and all secondary outcomes. The addition of each single biomarker to a model that included established risk factors improved the C statistic. For 10-year incident atherosclerotic cardiovascular disease in younger people (aged <65 years), the combination of high-sensitivity cardiac troponin I, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein resulted in a C statistic improvement from 0.812 (95% CI, 0.8021-0.8208) to 0.8194 (95% CI, 0.8089-0.8277). The combination of these biomarkers also improved reclassification compared with the conventional model. Improvements in risk prediction were most pronounced for the secondary outcomes of heart failure and all-cause mortality. The incremental value of biomarkers was greater in people aged 65 years or older vs younger people. Cardiovascular biomarkers were strongly associated with fatal and nonfatal cardiovascular events and mortality. The addition of biomarkers to established risk factors led to only a small improvement in risk prediction metrics for atherosclerotic cardiovascular disease, but was more favorable for heart failure and mortality.

Low rates of myocardial fibrosis and ventricular arrhythmias in recreational athletes after SARS-CoV-2 infection.

High rates of cardiac involvement were reported in the beginning of the coronavirus disease 2019 (COVID-19) pandemic. This led to anxiety in the athletic population. The current study was set up to assess the prevalence of myocardial fibrosis and ventricular arrhythmias in recreational athletes with the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Consecutive adult recreational athletes (≥18 years old, ≥4 h of mixed type or endurance sports/week) underwent systematic cardiac evaluation after a prior confirmed COVID-19 infection. Evaluation included clinical history, electrocardiogram (ECG), 5-day Holter monitoring, and cardiac magnetic resonance (CMR) imaging with simultaneous measurement of high-sensitive cardiac Troponin I. Data from asymptomatic or mildly symptomatic athletes (Group 1) were compared with those with moderate to severe symptoms (Groups 2-3). Furthermore, a comparison with a historical control group of athletes without COVID-19 (Master@Heart) was made. In total, 35 athletes (18 Group 1, 10 female, 36.9 ± 2.2 years, mean 143 ± 20 days following diagnosis) were evaluated. The baseline characteristics for the Group 1 and Groups 2-3 athletes were similar. None of the athletes showed overt myocarditis on CMR based on the updated Lake Louise criteria for diagnosis of myocarditis. The prevalence of non-ischemic late gadolinium enhancement [1 (6%) Group 1 vs. 2 (12%) Groups 2-3; p = 0.603] or ventricular arrhythmias [1 Group 1 athlete showed non-sustained ventricular tachycardia (vs. 0 in Groups 2-3: p = 1.000)] were not statistically different between the groups. When the male athletes were compared with the Master@Heart athletes, again no differences regarding these criteria were found. In our series of recreational athletes with prior confirmed COVID-19, we found no evidence of ongoing myocarditis, and no more detection of fibrosis or ventricular arrhythmias than in a comparable athletic pre-COVID cohort. This points to a much lower cardiac involvement of COVID-19 in athletes than originally suggested.

Myocardial extracellular volume derived from contrast-enhanced chest computed tomography in longitudinal evaluation of cardiac toxicity in patients treated with immune checkpoint inhibitors.

The immune-related adverse effects after immune checkpoint inhibitors (ICIs) treatment have always been a hot topic. Although the incidence of myocarditis is not high among the related adverse effects, the mortality rate is extremely high once it occurs. In the past, the risk of cancer therapy-related cardiac dysfunction (CTRCD) after drug treatment was evaluated based on imaging examinations, but this evaluation still had certain limitations. Currently, the extracellular volume (ECV) score measurement calculated using cardiac magnetic resonance T1 mapping has become a reliable method for evaluating myocardial toxicity and computed tomography (CT) examination may become an alternative. This study aimed to longitudinally evaluate the cardiac toxicity of patients treated with ICIs using myocardial ECV derived from contrast-enhanced chest CT. A total of 500 patients with III-IV lung cancer and esophageal cancer treated with ICIs were evaluated. Participants underwent baseline examination and at least 1 follow-up examination after treatment. Contrast-enhanced chest CT-ECV, left ventricular ejection fraction (LVEF), and measurement of cardiac troponin T (cTnT) were conducted before the first treatment, 3-6 months after the first treatment, and about 12 months after the first treatment, respectively. The ECV value of the middle part of the left ventricular septum was evaluated on CT venography and plain scan, the LVEF value was evaluated by color Doppler ultrasound, and the quantity of cTnT was detected by chemiluminescence. Cancer therapy-related cardiac dysfunction was recorded. The mean baseline LVEF value was 68.51%±4.81% (N0=500), and those of LVEF1, LVEF2, and LVEF3 were 68.77%±4.30%, 68.16%±3.59%, and 66.23%±4.20%, respectively (N1=500, N2=467, and N3=361, respectively). There was no significant difference between LVEF1, LVEF2, and LVEF0 (P1=0.095, P2=0.062), whereas LVEF3 was significantly lower than LVEF0 (P<0.001). The average baseline cTnT0 value was 7.42±3.95 (N0=500). The values of cTnT1, cTnT2, and cTnT3 were 10.05±11.40, 12.24±13.59, and 14.54±14.49, respectively (N1=500, N2=467, N3=361). The values of cTnT1, cTnT2, and cTnT3 were significantly higher than cTnT0 (P1<0.001, P2<0.001, P3<0.001). The average ECV0 was 47.14%±7.48% (N0=500). ECV1, ECV2, and ECV3 were 50.85%±6.79%, 53.44%±6.96% and 52.64%±7.58% respectively (N1=500, N2=467 and N3=361). ECV1, ECV2, and ECV3 were significantly higher than ECV0 (P1<0.001, P2<0.001, P3<0.001). CTRCD occurred in 49 patients. There were significant differences between the CTRCD (+) group and the CTRCD (-) group in cTnT1, cTnT2, and cTnT3 (P1<0.001, P2<0.001, and P3<0.001, respectively) and in ECV1, ECV2, and ECV3 (P1=0.039, P2=0.041, and P3=0.013, respectively). CT-ECV began to increase at the early stage after the treatment of ICIs. CT-ECV is a potential biomarker for dynamically monitoring the cardiac toxicity of tumor patients after receiving ICIs. ECV may be used to speculate the CTRCD caused by the treatment of ICIs.

The CRP troponin test (CTT) stratifies mortality risk in patients with non-ST elevation myocardial infarction (NSTEMI).

The C-reactive protein (CRP)-troponin-test (CTT) comprises simultaneous serial measurements of CRP and cardiac troponin and might reflect the systemic inflammatory response in patients with acute coronary syndrome. We sought to test its ability to stratify the short- and long-term mortality risk in patients with non-ST elevation myocardial infarction (NSTEMI). We examined 1,675 patients diagnosed with NSTEMI on discharge who had at least two successive measurements of combined CRP and cardiac troponin within 48 h of admission. A tree classifier model determined which measurements and cutoffs could be used to best predict mortality during a median follow-up of 3 years [IQR 1.8-4.3]. Patients with high CRP levels ( > 90th percentile, >54 mg/L) had a higher 30-day mortality rate regardless of their troponin test findings (16.7% vs. 2.9%, p < 0.01). However, among patients with "normal" CRP levels ( < 54 mg/L), those who had high troponin levels ( > 80th percentile, 4,918 ng/L) had a higher 30-day mortality rate than patients with normal CRP and troponin concentrations (7% vs. 2%, p < 0.01). The CTT test result was an independent predictor for overall mortality even after adjusting for age, sex, and comorbidities (HR = 2.28 [95% CI 1.56-3.37], p < 0.01 for patients with high troponin and high CRP levels). Early serial CTT results may stratify mortality risk in patients with NSTEMI, especially those with "normal" CRP levels. The CTT could potentially assess the impact of inflammation during myocardial necrosis on the outcomes of patients with NSTEMI and identify patients who could benefit from novel anti-inflammatory therapies.

Uniform or Sex-Specific Cardiac Troponin Thresholds to Rule Out Myocardial Infarction at Presentation

BackgroundMyocardial infarction can be ruled out in patients with a single cardiac troponin measurement. Whether use of a uniform rule-out threshold has resulted in sex differences in care remains unclear. ObjectivesThe purpose of this study was to evaluate implementation of a uniform rule-out threshold in females and males with possible myocardial infarction, and to derive and validate sex-specific thresholds. MethodsThe implementation of a uniform rule-out threshold (<5 ng/L) with a high-sensitivity cardiac troponin I assay was evaluated in consecutive patients presenting with possible myocardial infarction. The proportion of low-risk patients discharged from the emergency department and incidence of myocardial infarction or cardiac death at 30 days were determined. Sex-specific thresholds were derived and validated, and proportion of female and male patients were stratified as low-risk compared with uniform threshold. ResultsIn 16,792 patients (age 58 ± 17 years; 46% female) care was guided using a uniform threshold. This identified more female than male patients as low risk (73% vs 62%), but a similar proportion of low-risk patients were discharged from the emergency department (81% for both) with fewer than 5 (<0.1%) patients having a subsequent myocardial infarction or cardiac death at 30 days. Compared with a uniform threshold of <5 ng/L, use of sex-specific thresholds would increase the proportion of female (61.8% vs 65.9%) and reduce the proportion of male (54.8% vs 47.8%) patients identified as low risk. ConclusionsImplementation of a uniform rule-out threshold for myocardial infarction was safe and effective in both sexes. Sex-specific rule-out thresholds should be considered, but their impact on effectiveness and safety may be limited.

High-Sensitivity Cardiac Troponins in Patients With Chest Pain and Treatment With Oral Antineoplastic Agents Associated With Cardiovascular Toxicity

BackgroundKnowledge is limited on the clinical implications of high-sensitivity cardiac troponin (hs-cTn) measurements in patients treated with oral antineoplastic agents associated with cardiovascular side effects. This study investigated the diagnostic performance of hs-cTnT for myocardial infarction. MethodsAmong all visits to 7 different emergency departments (EDs) from December 9, 2010 to August 31, 2017, we included visits by patients presenting with chest pain who had ≥1 hs-cTnT measured. Patients treated with oral antineoplastic agents associated with cardiovascular toxicity were identified. Logistic regression models were used to estimate the performance of hs-cTnT for diagnosing myocardial infarction. ResultsWe identified 214,165 visits, of which 2695 (1.3%) occurred in patients with oral antineoplastic treatment associated with cardiovascular toxicity. Treatment was associated with a higher myocardial infarction incidence (8.2% vs 5.7%), but the overall diagnostic accuracy for a myocardial infarction was lower in patients with versus without treatment, paralleled by a lower specificity and PPV with the 0 h hs-cTnT rule-in cut-off of 52 ng/L (92.6% [95% CI: 91.6-93.6] vs 96.8% [95% CI: 96.8-96.9], and 42.8 [95% CI: 37.4-48.2] vs 49.5 [95% CI: 48.6-50.4], respectively). The majority (72%) of patients with treatment were assigned to an intermediate risk group, in whom the risk of myocardial infarction was reduced by 29% (OR 0.71, 95% CI: 0.57-0.89). ConclusionsDiagnostic accuracy of hs-cTnT for myocardial infarction is reduced among patients on treatment with oral antineoplastic agents associated with cardiovascular toxicity. Most patients would be assigned to an intermediate risk group, in whom only 4% will have a final myocardial infarction diagnosis.

Machine Learning for Myocardial Infarction Compared With Guideline-Recommended Diagnostic Pathways.

Collaboration for the Diagnosis and Evaluation of Acute Coronary Syndrome (CoDE-ACS) is a validated clinical decision support tool that uses machine learning with or without serial cardiac troponin measurements at a flexible time point to calculate the probability of myocardial infarction (MI). How CoDE-ACS performs at different time points for serial measurement and compares with guideline-recommended diagnostic pathways that rely on fixed thresholds and time points is uncertain. Patients with possible MI without ST-segment-elevation were enrolled at 12 sites in 5 countries and underwent serial high-sensitivity cardiac troponin I concentration measurement at 0, 1, and 2 hours. Diagnostic performance of the CoDE-ACS model at each time point was determined for index type 1 MI and the effectiveness of previously validated low- and high-probability scores compared with guideline-recommended European Society of Cardiology (ESC) 0/1-hour, ESC 0/2-hour, and High-STEACS (High-Sensitivity Troponin in the Evaluation of Patients With Suspected Acute Coronary Syndrome) pathways. In total, 4105 patients (mean age, 61 years [interquartile range, 50-74]; 32% women) were included, among whom 575 (14%) had type 1 MI. At presentation, CoDE-ACS identified 56% of patients as low probability, with a negative predictive value and sensitivity of 99.7% (95% CI, 99.5%-99.9%) and 99.0% (98.6%-99.2%), ruling out more patients than the ESC 0-hour and High-STEACS (25% and 35%) pathways. Incorporating a second cardiac troponin measurement, CoDE-ACS identified 65% or 68% of patients as low probability at 1 or 2 hours, for an identical negative predictive value of 99.7% (99.5%-99.9%); 19% or 18% as high probability, with a positive predictive value of 64.9% (63.5%-66.4%) and 68.8% (67.3%-70.1%); and 16% or 14% as intermediate probability. In comparison, after serial measurements, the ESC 0/1-hour, ESC 0/2-hour, and High-STEACS pathways identified 49%, 53%, and 71% of patients as low risk, with a negative predictive value of 100% (99.9%-100%), 100% (99.9%-100%), and 99.7% (99.5%-99.8%); and 20%, 19%, or 29% as high risk, with a positive predictive value of 61.5% (60.0%-63.0%), 65.8% (64.3%-67.2%), and 48.3% (46.8%-49.8%), resulting in 31%, 28%, or 0%, who require further observation in the emergency department, respectively. CoDE-ACS performs consistently irrespective of the timing of serial cardiac troponin measurement, identifying more patients as low probability with comparable performance to guideline-recommended pathways for MI. Whether care guided by probabilities can improve the early diagnosis of MI requires prospective evaluation. URL: https://www.clinicaltrials.gov; Unique identifier: NCT00470587.

Cardiac Biomarkers Aid in Differentiation of Kawasaki Disease from Multisystem Inflammatory Syndrome in Children Associated with COVID-19.

Kawasaki disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 show clinical overlap and both lack definitive diagnostic testing, making differentiation challenging. We sought to determine how cardiac biomarkers might differentiate KD from MIS-C. The International Kawasaki Disease Registry enrolled contemporaneous KD and MIS-C pediatric patients from 42 sites from January 2020 through June 2022. The study population included 118 KD patients who met American Heart Association KD criteria and compared them to 946 MIS-C patients who met 2020 Centers for Disease Control and Prevention case definition. All included patients had at least one measurement of amino-terminal prohormone brain natriuretic peptide (NTproBNP) or cardiac troponin I (TnI), and echocardiography. Regression analyses were used to determine associations between cardiac biomarker levels, diagnosis, and cardiac involvement. Higher NTproBNP (≥ 1500ng/L) and TnI (≥ 20ng/L) at presentation were associated with MIS-C versus KD with specificity of 77 and 89%, respectively. Higher biomarker levels were associated with shock and intensive care unit admission; higher NTproBNP was associated with longer hospital length of stay. Lower left ventricular ejection fraction, more pronounced for MIS-C, was also associated with higher biomarker levels. Coronary artery involvement was not associated with either biomarker. Higher NTproBNP and TnI levels are suggestive of MIS-C versus KD and may be clinically useful in their differentiation. Consideration might be given to their inclusion in the routine evaluation of both conditions.

Circulating Biomarkers for Monitoring Chemotherapy-Induced Cardiotoxicity in Children.

Most commonly diagnosed cancer pathologies in the pediatric population comprise leukemias and cancers of the nervous system. The percentage of cancer survivors increased from approximatively 50% to 80% thanks to improvements in medical treatments and the introduction of new chemotherapies. However, as a consequence, heart disease has become the main cause of death in the children due to the cardiotoxicity induced by chemotherapy treatments. The use of different cardiovascular biomarkers, complementing data obtained from electrocardiogram, echocardiography cardiac imaging, and evaluation of clinical symptoms, is considered a routine in clinical diagnosis, prognosis, risk stratification, and differential diagnosis. Cardiac troponin and natriuretic peptides are the best-validated biomarkers broadly accepted in clinical practice for the diagnosis of acute coronary syndrome and heart failure, although many other biomarkers are used and several potential markers are currently under study and possibly will play a more prominent role in the future. Several studies have shown how the measurement of cardiac troponin (cTn) can be used for the early detection of heart damage in oncological patients treated with potentially cardiotoxic chemotherapeutic drugs. The advent of high sensitive methods (hs-cTnI or hs-cTnT) further improved the effectiveness of risk stratification and monitoring during treatment cycles.

The CRP Troponin Test (CTT) stratifies mortality risk in patients with Non-ST Elevation Myocardial Infarction (NSTEMI)

Abstract Introduction The CRP-Troponin test (CTT) comprises serial measurements of both CRP and cardiac troponin and might reflect the systemic inflammatory response in patients with acute coronary syndrome. Here, we sought to test the ability of the CTT to stratify the short and long-term mortality risk in patients with non-ST elevation myocardial infarction (NSTEMI). Materials and Methods We examined 1,675 patients who were diagnosed with NSTEMI on discharge and had at least two successive measurements of combined CRP and cardiac troponin (up to 6 h apart), all within the first 48 hours of admission. We used a tree classifier model to determine which measurements and cutoffs could be used to best predict mortality during a median follow-up period of 3 years [IQR 1.8–4.3] (Figure 1A). Results Patients with high CRP levels (above 90th percentile, &amp;gt;54 mg/L) had a higher 30-day mortality rate regardless of their troponin test status (Figure 1B). However, among patients with "normal" CRP levels (&amp;lt;54 mg/L), those who had high troponin levels (above the 80th percentile, 4,918 ng/L) had a higher 30-day mortality rate compared with patients with normal CRP and troponin concentrations; 7% vs. 2%, p&amp;lt;0.01 (Figure 1B). A multivariate cox regression analysis showed that the CTT test result was an independent predictor for overall mortality even after adjusting for age, sex, and existing co-morbidities (Figure 1C). Conclusion Early serial CTT results may stratify mortality risk in patients with NSTEMI, especially in those presenting with "normal" CRP levels. The CTT is a simple diagnostic tool that could potentially assess the impact of inflammation during myocardial necrosis on the outcomes of patients with NSTEMI. The CTT might be used to identify patients who could benefit from novel anti-inflammatory therapies following myocardial infarction.Figure 1

Abstract 14314: Streamlining Cardiovascular Assessment Through Expert Intervention: Reduction in Superfluous Troponin I Testing Requests

Introduction: Cardiac troponin (cTn) measurements play a pivotal role in diagnosing and managing myocardial infarction (MI). Nonetheless, to prevent unnecessary expenditure, it is essential to optimize the usage of cTn testing. The AHA guidelines underscore the importance of minimizing low-value care, considering the widespread prevalence and substantial expenses related to cardiovascular disease. Hence, our study hypothesis is that expert-recommended cTn testing could effectively decrease unnecessary testing requests. Aims: This study aims to contrast the frequency of normal and of serial cTn I test results within a General University Hospital (GUH) setting and a specialized Cardiology University Hospital (CUH). Methods: Our cross-sectional study encompassed all cTn I tests performed at both GUH and CUH between November 2022 and March 2023. We excluded patients receiving postoperative care following invasive cardiac procedures and those engaged in research protocols. We categorized the study population by sex and age (&lt;60 or ≥60 years), as well as by whether the cTn I test was serially conducted (≥2 times within 24 hours). A serial cTn I test, as recommended by the 4th Universal definition of MI to detect any rise and/or fall, was considered a correct request. We utilized the chi-square test for categorical variables and the Mann-Whitney test for continuous data, setting a 5% significance level. Normal reference levels were &lt;16 and &lt;34 ng/L for women and men, respectively. Results: The study incorporated a total of 5,360 tests performed in GUH, with 46.2% on women and 60.9% on individuals aged ≥60 years. In CUH, 8,487 tests were conducted, with 42.0% on women and 53.8% on individuals aged ≥60 years. GUH displayed a higher proportion of normal cTn I test results compared to CUH (70% versus 45%, p &lt; 0.0001) and a lower percentage of serial cTn I tests (40.3% versus 53.4%, p &lt; 0.0001). Moreover, GUH demonstrated a lower median troponin value of 8 (2.5-33.8) versus 37 (7-455) in CUH, p &lt; 0.0001. Conclusions: The increased prevalence of normal cTn I results and the lower frequency of serial cTn I tests in GUH indicate potential economic inefficiencies related to excessive cTn I testing requests. Expert intervention could help in avoiding unnecessary cTnI test requests.

Investigation into the effect of hyperbaric hyperoxia on serum cardiac Troponin T levels as a biomarker of cardiac injury.

There is clinical equipoise as to whether hyperoxia is injurious to the myocardium, both in the setting of acute ischaemic insults and on the stable myocardium. This study examined the effect of extreme hyperoxia - in the form of hyperbaric oxygen treatment - on the myocardium through measurement of high-sensitivity cardiac troponin. Forty-eight individuals were enrolled to undergo a series of 30 exposures to hyperbaric oxygen for treatment of non-cardiac pathologies. High-sensitivity troponin T was measured before and after each session. There was no clinically significant difference in troponin measurements following acute or recurrent sequential exposures to extreme hyperoxia, despite the studied patient population having a high rate of previous ischaemic heart disease or cardiovascular risk factors. This study demonstrates that profound hyperoxaemia does not induce any measurable cardiac injury at a biochemical level. Neither is there a reduction in cardiac troponin to suggest a cardioprotective effect of hyperbaric hyperoxia. This provides some reassurance as to the cardiac safety of the routine use of hyperbaric oxygen treatment in management of non-cardiac pathology.

Late Mortality After Myocardial Injury in Critical Care Non-Cardiac Surgery Patients Using Machine Learning Analysis

Myocardial injury after noncardiac surgery (MINS) increases mortality within 30days. We aimed to evaluate the long-term impact of myocardial injury in a large cohort of patients admitted to intensive care after noncardiac surgery. All patients who stayed, at least, overnight with measurement of high-sensitive cardiac troponin were included. Clinical characteristics and occurrence of MINS were assessed between patients who died and survivors using chi-square test and Student ttest. Variables with p<0.01 in the univariate model were included in the Cox regression model to identify predictor variables. Survival decision tree (SDT), a machine learning model, was also used to find the predictors and their correlations. We included 2,230 patients with mean age of 63.8±16.3years, with most (55.6%) being women. The prevalence of MINS was 9.4% (209 patients) and there were 556 deaths (24.9%) in a median follow-up of 6.7years. Univariate analysis showed variables associated with late mortality, namely: MINS, arterial hypertension, previous myocardial infarction, atrial fibrillation, dementia, urgent surgery, peripheral artery disease (PAD), chronic health status, and age. These variables were included in the Cox regression model and SDT. The predictor variables of all-cause death were MINS (hazard ratio [HR] 2.21; 95% confidence interval [CI] 1.77 to 2.76), previous myocardial infarction (HR 1.47; 95% CI 1.14 to 1.89); urgent surgery (HR 1.24; 95% CI 1.01 to 1.52), PAD (HR 1.83; 95% CI 1.23 to 2.73), dementia (HR 2.54; 95% CI 1.86 to 3.46) and age (HR 1.05; 95% CI 1.04 to 1.06). SDT had the same predictors, except PAD. In conclusion, increased high-sensitive troponin levels in patients who underwent noncardiac surgery raised the risk of short and late mortality.

Troponin in early presenters to rule out myocardial infarction.

Whether a single cardiac troponin measurement can safely rule out myocardial infarction in patients presenting within a few hours of symptom onset is uncertain. The study aim was to assess the performance of troponin in early presenters. In patients with possible myocardial infarction, the diagnostic performance of a single measurement of high-sensitivity cardiac troponin I at presentation was evaluated and externally validated in those tested ≤3, 4-12, and >12 h from symptom onset. The limit-of-detection (2 ng/L), rule-out (5 ng/L), and sex-specific 99th centile (16 ng/L in women; 34 ng/L in men) thresholds were compared. In 41 103 consecutive patients [60 (17) years, 46% women], 12 595 (31%) presented within 3 h, and 3728 (9%) had myocardial infarction. In those presenting ≤3 h, a threshold of 2 ng/L had greater sensitivity and negative predictive value [99.4% (95% confidence interval 99.2%-99.5%) and 99.7% (99.6%-99.8%)] compared with 5 ng/L [96.5% (96.2%-96.8%) and 99.3% (99.1%-99.4%)]. In those presenting ≥3 h, the sensitivity and negative predictive value were similar for both thresholds. The sensitivity of the 99th centile was low in early and late presenters at 71.4% (70.6%-72.2%) and 92.5% (92.0%-93.0%), respectively. Findings were consistent in an external validation cohort of 7088 patients. In early presenters, a single measurement of high-sensitivity cardiac troponin I below the limit of detection may facilitate the safe rule out of myocardial infarction. The 99th centile should not be used to rule out myocardial infarction at presentation even in those presenting later following symptom onset.

Label-Free Detection of Cardiac Biomarkers: A Review on Microfluidic Electrochemical Biosensors.

Biosensors are valuable tools for the detection of biological species, including cells, pathogens, proteins, and other biological molecules. Biosensing devices integrated with microfluidics not only allow for easier sample preparation, portability, and reduced detection time and cost but also offer unique features such as label-free detection and improved sensitivity. Cardiovascular diseases (CVDs), particularly acute myocardial infarction, which is considered one of the main causes of death, are currently diagnosed by electrocardiography (ECG), which has been proven to be inadequate. To overcome the limitations of ECG, the efficient detection of cardiac biomarkers and specifically the measurement of cardiac troponins (cTnT and cTnI) are suggested. This review aims to expound on microfluidics, the most recent materials to develop these devices, and their application in medical diagnosis, particularly in CVD detection. Moreover, we will explore some of the prevalent and last readout methods to investigate in-depth electrochemical label-free detection methods for CVDs, primarily based on voltammetry and electrochemical impedance spectroscopy, with the main focus on structural details.

Diagnostic Accuracy of Clinical Pathways for Suspected Acute Myocardial Infarction in the Out-of-Hospital Environment

Chest pain is one of the most common reasons for emergency ambulance calls. Patients are routinely transported to the hospital to prevent acute myocardial infarction (AMI). We evaluated the diagnostic accuracy of clinical pathways in the out-of-hospital environment. The Troponin-only Manchester Acute Coronary Syndromes decision aid and History, ECG, Age, Risk Factors, Troponin score require cardiac troponin (cTn) measurement, whereas the History and ECG-only Manchester Acute Coronary Syndromes decision aid and History, ECG, Age, Risk Factors score do not. We conducted a prospective diagnostic accuracy study at 4 ambulance services and 12 emergency departments between February 2019 and March 2020. We included patients who received an emergency ambulance response in whom paramedics suspected AMI. Paramedics recorded the data required to calculate each decision aid and took venous blood samples in the out-of-hospital environment. Samples were tested using a point-of-care cTn assay (Roche cobas h232) within 4 hours. The target condition was a diagnosis of type 1 AMI, adjudicated by 2 investigators. Of 817 included participants, 104 (12.8%) had AMI. Setting the cutoff at the lowest risk group, Troponin-only Manchester Acute Coronary Syndromes had 98.3% sensitivity (95% confidence interval 91.1% to 100%) and 25.5% specificity (21.4% to 29.8%) for type 1 AMI. History, ECG, Age, Risk Factors, Troponin had 86.4% sensitivity (75.0% to 98.4%) and 42.2% specificity (37.5% to 47.0%); History and ECG-only Manchester Acute Coronary Syndromes had 100% sensitivity (96.4% to 100%) and 3.1% specificity (1.9% to 4.7%), whereas History, ECG, Age, Risk Factors had 95.1% sensitivity (88.9% to 98.4%) and 12.1% specificity (9.8% to 14.8%). With point-of-care cTn testing, decision aids can identify patients at a low risk of type 1 AMI in the out-of-hospital environment. When used alongside clinical judgment, and with appropriate training, such tools may usefully enhance out-of-hospital risk stratification.

Breakthrough in acute coronary syndrome diagnostics – transdermal troponin assessment

Introduction and purpose:&#x0D; The measurement of cardiac troponins, besides ECG and basic patient examination, is a vital component of the diagnosis and management of patients with acute coronary syndrome (ACS), including unstable angina (UA), non-ST and ST elevation myocardial infarction (NSTEMI, STEMI). Traditionally cardiac troponins have been measured through blood samples, but a new method of transdermal wrist measurement has emerged as a promising alternative. The potential benefits of transdermal troponin measurement are numerous. First and foremost, the non-invasive nature of the method means that patients can be diagnosed “on the spot” and monitored in real time without the need for repeated blood draws, vastly reducing the time for diagnosis and patient qualification for invasive treatment, percutaneous coronary intervention - PCI, if needed. The coronary syndrome is the number 1 cause of death in developed countries which includes morbidity and mortality. With the invention of transdermal troponin assessment device, we can increase the life expectancy and the quality of life in the group of patients with acute coronary syndrome and most importantly, decrease the total turnaround time of diagnosis and significantly reduce the workload in the emergency department.

Antibody-mediated interferences affecting cardiac troponin assays: recommendations from the IFCC Committee on Clinical Applications of Cardiac Biomarkers.

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.

Fragmentation of human cardiac troponin T after acute myocardial infarction

BackgroundBlood measurement of cardiac troponin T (cTnT) is one of the most widespread methods of acute myocardial infarction (MI) diagnosis. cTnT degradation may have a significant influence on the precision of cTnT immunodetection; however, there are no consistent data describing the level and sites of cTnT proteolysis in the blood of MI patients. In this study, we bordered major cTnT fragments and quantified their relative abundance in the blood at different times after MI. MethodsSerial heparin plasma samples were collected from 37 MI patients 2–37 h following the onset of MI. cTnT and its fragments were studied by western blotting and immunofluorescence analysis using monoclonal antibodies specific to various cTnT epitopes. ResultscTnT was present in the blood of MI patients as 23 proteolytic fragments with an apparent molecular mass of ∼ 8–37 kDa. Two major sites of cTnT degradation were identified: between amino acid residues (aar) 68 and 69 and between aar 189 and 223.Analysis of the abundance of cTnT fragments showed an increase in the fraction of free central fragments in the first few hours after MI, while the fraction of the C-terminal fragments of cTnT remained almost unchanged. ConclusioncTnT progressively degrades after MI and appears in the blood as a mixture of 23 proteolytic fragments. The cTnT region approximately bordered by aar 69–158 is a promising target for antibodies used for measurement of total cTnT.

Diagnostic performance of a device for acoustic heart sound analysis in patients with suspected myocardial infarction

BackgroundAs only a small proportion of patients with chest pain suffers from myocardial infarction (MI), safe rule-out of MI is of immense importance. Recently an ultrasensitive microphone performing diastolic heart...