Non-Classical Secretion: A Possible Mechanism to Explain Cardiac Troponin Elevations in the Absence of Acute Myocardial Infarction.
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SUBMITTER: Gonzalez-Rayas JM
PROVIDER: S-EPMC9006998 | biostudies-literature | 2022 Apr
REPOSITORIES: biostudies-literature
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Non-Classical Secretion: A Possible Mechanism to Explain Cardiac Troponin Elevations in the Absence of Acute Myocardial Infarction.
Gonzalez-Rayas Jose Manuel JM Hernandez-Hernandez Jose Ascencion JA Lopez-Sanchez Rosa Del Carmen RDC Rayas-Gomez Ana Lilia AL Gonzalez-Yanez Jose Manuel JM
Arquivos brasileiros de cardiologia 20220401 4
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Project description:BackgroundAlthough the 99th percentile is the recommended diagnostic threshold for myocardial infarction, some guidelines also advocate the use of higher troponin thresholds to rule in myocardial infarction at presentation. It is unclear whether the magnitude or change in troponin concentration can differentiate causes of myocardial injury and infarction in practice.MethodsIn a secondary analysis of a multicenter randomized controlled trial, we identified 46 092 consecutive patients presenting with suspected acute coronary syndrome without ST-segment-elevation myocardial infarction. High-sensitivity cardiac troponin I concentrations at presentation and on serial testing were compared between patients with myocardial injury and infarction. The positive predictive value and specificity were determined at the sex-specific 99th percentile upper reference limit and rule-in thresholds of 64 ng/L and 5-fold of the upper reference limit for a diagnosis of type 1 myocardial infarction.ResultsTroponin was above the 99th percentile in 8188 patients (18%). The diagnosis was type 1 or type 2 myocardial infarction in 50% and 14% and acute or chronic myocardial injury in 20% and 16%, respectively. Troponin concentrations were similar at presentation in type 1 (median [25th-75th percentile] 91 [30-493] ng/L) and type 2 (50 [22-147] ng/L) myocardial infarction and in acute (50 [26-134] ng/L) and chronic (51 [31-130] ng/L) myocardial injury. The 99th percentile and rule-in thresholds of 64 ng/L and 5-fold upper reference limit gave a positive predictive value of 57% (95% CI, 56%-58%), 59% (58%-61%), and 62% (60%-64%) and a specificity of 96% (96%-96%), 96% (96%-96%), and 98% (97%-98%), respectively. The absolute, relative, and rate of change in troponin concentration were highest in patients with type 1 myocardial infarction (P<0.001 for all). Discrimination improved when troponin concentration and change in troponin were combined compared with troponin concentration at presentation alone (area under the curve, 0.661 [0.642-0.680] versus 0.613 [0.594-0.633]).ConclusionsAlthough we observed important differences in the kinetics, cardiac troponin concentrations at presentation are insufficient to distinguish type 1 myocardial infarction from other causes of myocardial injury or infarction in practice and should not guide management decisions in isolation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01852123.
| S-EPMC8360674 | biostudies-literature
Project description:Although guidelines recommend fixed cardiac troponin thresholds for the diagnosis of myocardial infarction, troponin concentrations are influenced by age, sex, comorbidities and time from symptom onset. To improve diagnosis, we developed machine learning models that integrate cardiac troponin concentrations at presentation or on serial testing with clinical features and compute the Collaboration for the Diagnosis and Evaluation of Acute Coronary Syndrome (CoDE-ACS) score (0-100) that corresponds to an individual's probability of myocardial infarction. The models were trained on data from 10,038 patients (48% women), and their performance was externally validated using data from 10,286 patients (35% women) from seven cohorts. CoDE-ACS had excellent discrimination for myocardial infarction (area under curve, 0.953; 95% confidence interval, 0.947-0.958), performed well across subgroups and identified more patients at presentation as low probability of having myocardial infarction than fixed cardiac troponin thresholds (61 versus 27%) with a similar negative predictive value and fewer as high probability of having myocardial infarction (10 versus 16%) with a greater positive predictive value. Patients identified as having a low probability of myocardial infarction had a lower rate of cardiac death than those with intermediate or high probability 30 days (0.1 versus 0.5 and 1.8%) and 1 year (0.3 versus 2.8 and 4.2%; P < 0.001 for both) from patient presentation. CoDE-ACS used as a clinical decision support system has the potential to reduce hospital admissions and have major benefits for patients and health care providers.
| S-EPMC10202804 | biostudies-literature
Project description: Not available
| S-EPMC9951014 | biostudies-literature
Project description:ObjectivesElevations of cardiac troponin T (cTnT) levels are common after strenuous exercise. We assessed whether the composition of cTnT release after marathon race differs from that of acute myocardial infarction (MI).MethodsTroponin composition was analysed in plasma samples taken from 45 runners after marathon race and from 84 patients with type 1 MI. The concentration of long cTnT (intact and mildly fragmented cTnT) was measured with a novel upconversion luminescence immunoassay, total cTnT with a commercial high-sensitivity cTnT assay, and the ratio of long to total cTnT (troponin ratio) was determined as a measure of troponin fragmentation.ResultsTotal cTnT exceeded the upper reference limit (>14 ng/L) in 37 (82%) runners. Troponin ratio was lower in runners ((IQR) 0.17 (0.11-0.24) vs 0.62 (0.29-0.96), p<0.001). With increasing troponin release the troponin ratio decreased (r=-0.497, p<0.001) in marathon runners and the concentration of long cTnT remained in all runners below 8.4 ng/L. In contrast to marathon runners, troponin ratio increased (r=0.565, p<0.001) with the increase of cTnT release in patients with MI. The median total and long cTnT concentrations were lower in marathon runners than in patients with MI (25 ng/L vs 835 ng/L and 4.1 vs 385 ng/L, p<0.001 for both).ConclusionIn contrast to type 1 MI, only a small fraction of circulating cTnT exists as intact cTnT or long molecular forms after strenuous exercise and the difference in troponin composition is more pronounced in runners with higher troponin release.Trial registration numberNCT06000930.
| S-EPMC11574483 | biostudies-literature
Project description:BackgroundRuling out acute myocardial infarction (AMI) in the emergency department (ED) is challenging. Studies have shown that a high-sensitivity cardiac troponin T (hs-cTnT) <5 ng/L or <6 ng/L at presentation (0 h) can be used to rule out AMI. The objective of this study was to identify whether an even higher hs-cTnT threshold can be used for a safe rule out of AMI in the ED.MethodsThe derivation cohort consisted of 24,973 ED patients with a primary complaint of chest pain. In this cohort, we identified the highest concentration of 0 h hs-cTnT that corresponded to a negative predictive value (NPV) of ≥99.5% for the primary endpoint of AMI/all-cause death within 30 days and the secondary endpoint of all-cause death within one year. The results were validated in two cohorts consisting of 132,021 and 1167 ED chest pain patients.ResultsThe 0 h hs-cTnT threshold corresponding to a NPV of ≥99.5% for the primary endpoint was <9 ng/L (NPV: 99.6% and 95% CI: 99.5-99.7). This cutoff provided a sensitivity of 96.2% (95% CI: 95.2-97.1) and identified 59.7% of the patients as low risk compared to 35.8% and 43.9% with a 0 h hs-cTnT <5 ng/L and <6 ng/L, respectively. The results were similar in the validation cohorts and seemed to perform even better in patients where the 0 h hs-cTnT was measured >3 h after symptom onset and in those with a nonischemic ECG and nonhigh risk history.ConclusionsA 0 h hs-cTnT cutoff of <9 ng/L safely rules out AMI/death within 30 days in a majority of chest pain patients and is a more effective strategy than the currently recommended <5 ng/L and <6 ng/L cutoffs. This trial is registered with NCT03421873.
| S-EPMC10985641 | biostudies-literature
Project description:Acute myocardial infarction (AMI) is a severe cardiovascular disease characterized by heart muscle damage due to inadequate blood supply, leading to a life-threatening risk of heart attack. Herein, we report on the design of polyaminophenol-based thin film functional polymers and their thorough optimization by electrochemical, spectroscopic, and microscopic techniques to develop a high-performance point-of-care voltammetric monitoring system. Molecularly imprinted polymer-based cTnI-responsive nanocomposite materials were prepared on an electrode surface by imprinting a specific cTnI epitope, integrating polyaminophenol electrodeposition, along with gold nanoparticles (AuNPs) and graphene quantum dots (GQDs). The characterization techniques, including cyclic and square wave voltammetries, electrochemical impedance spectroscopy, atomic force microscopy, fluorescence microscopy, attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), and contact angle measurements proved the efficient fabrication of the voltammetric monitoring system relying on cTnI-responsive functional thin films. The sensing platform prepared with the optimized nanocomposite composition of AuNPs, GQDs, and molecularly imprinted polymers exhibited very high sensitivity, reproducibility, specificity, and affinity toward cTnI. The sensor showed a storage stability of 30 days, demonstrating great potential for use in early and point-of-care diagnosis of AMI with its 18 min detection time.
| S-EPMC11256321 | biostudies-literature
Project description:Serological assessment of cardiac troponins (cTn) is the gold standard to assess myocardial injury in clinical practice. A greater magnitude of acutely or chronically elevated cTn concentrations is associated with lower event-free survival in patients and the general population. Exercise training is known to improve cardiovascular function and promote longevity, but exercise can produce an acute rise in cTn concentrations, which may exceed the upper reference limit in a substantial number of individuals. Whether exercise-induced cTn elevations are attributable to a physiological or pathological response and if they are clinically relevant has been debated for decades. Thus far, exercise-induced cTn elevations have been viewed as the only benign form of cTn elevations. However, recent studies report intriguing findings that shed new light on the underlying mechanisms and clinical relevance of exercise-induced cTn elevations. We will review the biochemical characteristics of cTn assays, key factors determining the magnitude of postexercise cTn concentrations, the release kinetics, underlying mechanisms causing and contributing to exercise-induced cTn release, and the clinical relevance of exercise-induced cTn elevations. We will also explain the association with cardiac function, correlates with (subclinical) cardiovascular diseases and exercise-induced cTn elevations predictive value for future cardiovascular events. Last, we will provide recommendations for interpretation of these findings and provide direction for future research in this field.
| S-EPMC8663527 | biostudies-literature
Project description:ObjectiveTo examine changes in concentration, time-to-peak and the ensuing half-life of cardiac biomarkers in patients with myocardial infarction.MethodsBlood sampling was performed every third hour within 24 h after percutaneous coronary intervention (PCI) on a cohort of patients with ST elevation myocardial infarction. Cardiac troponin (cTn) was measured by the Dimension Vista, Vitros, Atellica, and Alinity high-sensitivity (hs) cTnI assays, and the Elecsys hs-cTnT assay. Further, creatine kinase (CK), myoglobin, creatine kinase MB (CKMB) and other biomarkers were analyzed.ResultsA total of 36 patients completed blood sampling (median age 60 years, IQR 56.4-66.5 years; seven women, 19.4%). Hs-cTnI measured by the Vitros assay was the first hs-cTn to peak at 9.1 h (95%-CI 6.2-10.1) after PCI and 11.7 h (95%-CI 10.4-14.8) after symptoms onset. There were no notable differences between hs-cTn assays in regard to time-to-peak. Also, Vitros hs-cTnI reached the highest median ratio of concentration to upper reference level of nearly 2,000. The median half-life from peak concentration ranged from 7.6 h for myoglobin (CI 6.8-8.6) to 17.8 h for CK (CI 6.8-8.6). For hs-cTn assays the median T½ ranged from 12.4 h for the Vista hs-cTnI assay (95%-CI 11.0-14.1 h) to 17.3 h for the Elecsys hs-cTnT (95%-CI 14.9-20.8 h).ConclusionsThis study updates knowledge on the kinetics of cardiac biomarkers in current clinical use. There was no notable difference in trajectories, time-to-peak or half-life between hs-cTn assays.
| S-EPMC10432699 | biostudies-literature
Project description:ObjectivesWe aimed to assess the diversity and practices of existing studies on several assays and algorithms for serial measurements of high-sensitivity cardiac troponin (hs-cTn) for risk stratification and the diagnosis of myocardial infarction (MI) and 30-day outcomes in patients suspected of having non-ST-segment elevation MI (NSTEMI).MethodsWe searched multiple databases including MEDLINE, EMBASE, Science Citation Index, the Cochrane Database of Systematic Reviews and the CENTRAL databases for studies published between January 2006 and November 2021. Studies that assessed the diagnostic accuracy of serial hs-cTn testing in patients suspected of having NSTEMI in the emergency department (ED) were eligible. Data were analysed using the scoping review method.ResultsWe included 86 publications, mainly from research centres in Europe, North America and Australasia. Two hs-cTn assays, manufactured by Abbott (43/86) and Roche (53/86), dominated the evaluations. The studies most commonly measured the concentrations of hs-cTn at two time points, at presentation and a few hours thereafter, to assess the two-strata or three-strata algorithm for diagnosing or ruling out MI. Although data from 83 studies (97%) were prospectively collected, 0%-90% of the eligible patients were excluded from the analysis due to missing blood samples or the lack of a final diagnosis in 53 studies (62%) that reported relevant data. Only 19 studies (22%) reported on head-to-head comparisons of alternative assays.ConclusionEvidence on the accuracy of serial hs-cTn testing was largely derived from selected research institutions and relied on two specific assays. The proportions of the eligible patients excluded from the study raise concerns about directly applying the study findings to clinical practice in frontline EDs.Prospero registration numberCRD42018106379.
| S-EPMC9685223 | biostudies-literature
Project description:Glucose is a universally available inexpensive biomarker, which is increased as part of the physiological stress response to acute myocardial infarction (AMI) and may therefore help in its early diagnosis. To test this hypothesis, glucose, high-sensitivity cardiac troponin (hs-cTn) T, and hs-cTnI were measured in consecutive patients presenting with acute chest discomfort to the emergency department (ED) and enrolled in a large international diagnostic study (NCT00470587). Two independent cardiologists centrally adjudicated the final diagnosis using all clinical data, including serial hs-cTnT measurements, cardiac imaging and clinical follow-up. The primary diagnostic endpoint was index non-ST-segment elevation MI (NSTEMI). Prognostic endpoints were all-cause death, and cardiovascular (CV) death or future AMI, all within 730-days. Among 5639 eligible patients, NSTEMI was the adjudicated final diagnosis in 1051 (18.6%) patients. Diagnostic accuracy quantified using the area under the receiver-operating characteristics curve (AUC) for the combination of glucose with hs-cTnT and glucose with hs-cTnI was very high, but not higher versus that of hs-cTn alone (glucose/hs-cTnT 0.930 [95% CI 0.922-0.937] versus hs-cTnT 0.929 [95% CI 0.922-0.937]; glucose/hs-cTnI 0.944 [95% CI 0.937-0.951] versus hs-cTnI 0.944 [95% CI 0.937-0.951]). In early-presenters, a dual-marker strategy (glucose < 7 mmol/L and hs-cTnT < 5/hs-cTnI < 4 ng/L) provided very high and comparable sensitivity to slightly lower hs-cTn concentrations (cTnT/I < 4/3 ng/L) alone, and possibly even higher efficacy. Glucose was an independent predictor of 730-days endpoints. Our results showed that a dual marker strategy of glucose and hs-cTn did not increase the diagnostic accuracy when used continuously. However, a cutoff approach combining glucose and hs-cTn may provide diagnostic utility for patients presenting ≤ 3 h after onset of symptoms, also providing important prognostic information.
| S-EPMC10480296 | biostudies-literature