Troponin Research Articles

A-315 Cardiac Troponin Concentrations in Pediatric Patients Infected with Respiratory Syncytial Virus

Abstract Background Respiratory syncytial virus (RSV) is associated with considerable morbidity and mortality in pediatric patients. Cardiac troponin I (TnI) has been shown to increase in patients with acute respiratory illness, including COVID-19. The impact of RSV infection on circulating TnI has been formally demonstrated in the literature. The goal of this study was to assess the relationship between TnI and respiratory syncytial virus (RSV) in pediatric patients. Methods A prospective study was conducted at St. Louis Children’s Hospital from October 2023 to February 2024. Patients older than 6 months who presented to the ED and had a CBC ordered within 6 hours of testing positive for RSV on the Biofire® FilmArray® Respiratory Panel were enrolled. Patients with Rhinovirus, Enterovirus, Streptococcus pneumoniae, or Adenovirus infections were included as controls. Remnant EDTA specimens were tested on an Abbott ARCHITECT i2000 for high sensitivity TnI (hs-TnI) with a limit of detection of 1.4 ng/L and a limit of quantitation of 3.5 ng/L. 99% upper reference limits from the CALIPER database on the Abbott of <7 ng/L were used as a threshold for positive results. The electronic medical record (EPIC) was assessed for demographic information and outcomes including length of stay (LOS), intensive care unit (ICU) length of stay, requirement of supplemental oxygen, white blood cell count (WBC), and creatinine. Results A total of 103 patients had RSV and 35 had other respiratory infections (ORI). The average age for the RSV positive group was 2.3 and for the ORI group was 2.4. Males made up 61% of the RSV+ group and 51% of the ORIs. 93 patients in the RSV group were admitted. The median TnI for RSV patients was 1.4 (IQR, 1.2-2.9) and for ORIs was 1.4 (IQR, 1.4-6.8). TnI was measurable in 58% of those with RSV and 54% in ORIs. We next assessed the correlation between hospital LOS and TnI in RSV+ patients, with a Pearson r of 0.42 (95% CI= 0.23-0.58). There was no correlation between WBC and LOS (r=-0.04, 95% CI=-0.25-0.17). There was also no correlation between TnI and WBCs or creatinine. Of admitted patients, 44 (47%) in the RSV group were in the ICU compared to 18 (51.4%) in those with ORIs. RSV+ patients that required ICU treatment had comparable TnI (1.4, IQR, 0.9-3.5) to those that didn’t require ICU stay (1.4, IQR, 0.75-1.5). There was no correlation between ICU LOS and TnI in RSV+ patients (r=-0.08, 95% CI=-0.39-0.24). There was a significant difference in mean TnI concentrations in RSV+ patients that required supplemental oxygen (8.7, 95% CI: 0-19) versus those that did not (1.7, 95% CI: 1.1-2.4). Conclusions There was no difference in TnI in patients hospitalized for RSV relative to ORIs. While TnI concentration was associated with LOS, there were minimally other associations between TnI and outcomes in patients hospitalized with RSV. While TnI elevations are associated with acute respiratory infections in adults, the impact on pediatric patients is not as clear. Future investigation is needed to understand how severe respiratory infections impact pediatric cardiac function.

A-016 Can You Believe Your Troponin? Using Laboratory Automation and Programmed Rules to Reduce Non-Repeatable False Positive Troponin Results

Abstract Background Cardiac troponin is currently the standard biomarker for evaluating patients with suspected acute coronary syndrome. Like all immunoassays, troponin testing is susceptible to non-repeatable positive results. Because this can cause a clinical challenge, we assessed our false positive rate by manipulating the timing and conditions of repeat troponin testing. Methods A prospective observational study established the repeatability failure (RF) rate in three scenarios, where a suspicious initial result prompts a repeat test. Protocol 1: We programed our middleware (Remisol, Beckman Coulter) to route the specimen to online storage after initial testing. After a 120-minute delay, the specimen was automatically retrieved from storage and tested again. Protocol 2: We programmed DxI 800 systems (Beckman Coulter) to aspirate a specimen reserve volume sufficient for two test replicates simultaneously. Protocol 3: We restricted repeat testing to 18-50 ng/L where the majority of RF occurred. To analyze RF in 4 and 18 ng/L interval (limit of reporting and URL, respectively), an absolute 3.5 ng/L bias was considered an RF. For specimens >18 ng/L, a difference of ±4.0 SD difference between replicates with a CV of 7% was a RF, equating to a relative difference of 28% (Method 1). Method 2 used a relative difference of 35% for RF. Method 3 defined RF as a critical difference of z×√2×SDanalytical where z=3.5 and SD=1.8 for results <19 ng/L and SD for results ≥19 ng/L were calculated from a fixed 7% CV for each result. A z-value of 3.5 represents a probability of 0.0005 (5 in 10,000). Results Using Protocol 1, RF rate was significantly higher in delayed repeat testing (1.6%, CI 1.5-1.8, n=23,525) compared to immediate repeat testing (0.4%, CI 0.4-0.5, n=14,880, p<0.0001) in two-tailed analysis. Because the first result was more commonly larger than the second (77.7% v. 52.2%, respectively), one-tailed analysis was used and found RF in delayed repeat testing was 0.9% (CI 0.8-1.0) v. immediate repeat testing (0.4%, CI 0.3-0.4, p<0.0001). A similar percentage of results were found in the 18-50 ng/L range in delayed testing (88.6%) v. immediate repeat (86.8%). Protocol 2 (with one-tailed analysis) yielded similar RF rates: 0.8%, CI 0.8-1.0 v. 0.3%, CI 0.3-0.4, delayed and immediate repeat testing, respectively. Protocol 3 yielded RF rate of 0.6%, CI 0.5-0.7 v. 0.2%, CI 0.2-0.3, delayed and immediate repeat testing, respectively, with all p-values <0.0001. Conclusions By programming auto-repeating hsTnI testing only in the 18-50 ng/L range, we found >80% of specimens with potential RF results could be retested using either the delayed- or immediate-repeat protocols. This suggests automated protocols could repeat testing with potential RFs without staff intervention or increasing container movement on the automation line. Reagent usage because of repeat testing could be conserved by limiting repeat testing to specimens most likely to create provider confusion. Rules to automate selected retesting of hsTnI in testing systems and/or middleware can enhance quality of results without human intervention and subsequent burden on staff, reduce reagent waste and enhance provider decision making in a critical population.

A-005 Comparison of Performance of High Sensitive Troponin I (cTNIH) by “Point of care” (POC) and Automated cTNIH Immunoassays in Patients at Low Risk of Heart Attack in a Chilean Emergency Unit; Impact on E.R Department Efficiency

Abstract Background Most cases of death from Acute Myocardial Infarction (AMI) occur in the first hours after the manifestation of clinical symptoms, constituting 40 to 65% in the first hour and approximately 80% in the first 24 hours. For the safe, effective, and rapid diagnosis of a patient with suspected AMI, international guidelines recommend that it be done based on clinical symptoms, together with electrocardiogram and analysis of biomarkers in the context of suspected of non-ST-elevation myocardial infarction (NSTEMI). Troponins are the biomarkers of choice with level A level evidence and the ability to perform screening in patients complaining of chest pain and refer it to the correct clinical approach based on the 0h/1h algorithm. To date, the successful clinical implementation of these rapid algorithms is restricted to hospitals working with well-defined workflows and a robust central laboratory structure. The Atellica® vTLi analyzer is based on the chemiluminescence methodology for the quantification of hs-cTnI levels with low sample volume, low complexity, and may enable the rapid management of patients with chest pain and application of 0h/1h algorithm. Objectives The aim of the study is to evaluate clinical performance in effectiveness and efficiency of the hs-cTnI Atellica® vTLi point of care test to rule out acute myocardial infarction in subjects with low-risk chest pain established with a validated predictive rule, in an adult-Chilean emergency unit, compared to clinical evaluation and the commonly used ADVIA Centaur® troponin test. Methods Descriptive, observational, longitudinal study. Patients over 18 years of age, consulting with acute chest pain of at least one hour from symptom onset and a HEART SCORE less than or equal to 3 points were recruited. A venous blood sample was requested for hs-cTnI analysis by Atellica® vTLi Siemens Healthineers and ADVIA Centaur® Siemens Healthineers. The time difference between sample collection and start of sample analysis; the time difference between sample collection and release of sample results was recorded and the concordance between the two results was determined. Results 50 subjects were included in the study. The difference between blood sampling and start of sample analysis was 5 minutes with Atellica® vTLi POC and 68 minutes with ADVIA Centaur®. The concordance of hs-cTnI Atellica® vTLi POC and ADVIA Centaur® was 94% for predicting medical discharge and confirmed acute myocardial infarction. Conclusions The study findings support the safety and efficiency of the hs-cTnI POC test by providing faster results than central laboratory tests with the same analytical quality, with direct impact on reducing care times in patients consulting for low-risk chest pain.

Management of myocardial infarction with non-obstructive coronary arteries (MINOCA) in Germany: a single-center study on hospital resources and healthcare economics.

Patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) present as a main feature ≤50% stenosis upon angiography despite clinical symptoms and biomarker elevation related to acute coronary syndrome. Due to broad availability of high sensitivity troponin testing as well as invasive and non-invasive imaging, this clinical entity receives increasing clinical awareness. We aimed to investigate the in-hospital work flow and economic impact of MINOCA vs. MICAD (myocardial infarction with obstructive coronary artery disease) patients and related clinical outcomes in a single-center patient collective of a large university heart center in Germany. We retrospectively screened and analyzed all patients who were admitted to our hospital under the suspicion of an acute coronary syndrome within a 12-month period (2017-2018) for further diagnostics and treatment. All included patients showed a pathological troponin elevation and received invasive coronary angiography for acute coronary syndrome. Associated in-hospital costs, procedural and various clinical parameters as well as timelines and parameters of work-flow were obtained. After screening of 3,021 patients, we included 660 patients with acute coronary syndrome. Of those, 118 patients were attributed to the MINOCA-group. 542 patients presented with a "classical" myocardial infarction (MICAD group). MINOCA patients were less frail, more likely female, but showed no relevant difference in age or other selected comorbidities except for fewer cases of diabetes. In-hospital mortality (11% vs. 0%; p < 0.001) and 30-day mortality (17.3% vs. 4.2%; p < 0.001) after the index event were significantly higher in the "classical" myocardial infarction group (MICAD)- Despite a shorter overall length of hospital stay (9.5 ± 8.7 days vs. 12.3 ± 10.5 days, p < 0.01) with a significantly shorter duration of high care monitoring (intensive/intermediate care or chest pain units) (2.4 ± 2.1 days vs. 4.7 ± 3.3 days, p < 0.01) MINOCA patients consumed a relevant contingent of hospital resources. Thus, in a 12-months period a total sum of almost 300 days was attributed to high care monitoring for MINOCA patients with a mean difference of approximately 50% compared to patients with classical myocardial infarction. With average and median costs of 50% less per index, MINOCA treatment costs were lower compared to the MICAD group in the hospital reimbursement system of Germany. Consequently, MINOCA treatment was not associated with a relevant profit for these expanses and a relevant share of nearly 40% of the total costs was generated due to high care monitoring. In light of lower mortality than MICAD and growing scarcity of staff, financial and capacity resources the clinical symptom complex of MINOCA should be put under particular consideration for refining care concepts and resource allocation.

The Association Between Elevated Myocardial Injury-Related Biomarker (TnI) and Increased Mortality in Patients With Severe Fever With Thrombocytopenia Syndrome.

The objective of this study was to investigate the dynamic profiles of myocardial injury biomarkers and their association with mortality in patients with severe fever with thrombocytopenia syndrome (SFTS). A retrospective cohort study. Union Hospital in Wuhan, China. A total of 580 patients with SFTS, observed between May 2014 and December 2021, were included in the final analysis. None. In total, 580 patients with SFTS were enrolled in the study, comprised of 469 survivors and 111 nonsurvivors, with a 21-day fatality rate of 19.1%. The elevation of troponin I (TnI) was observed in 61.6% patients (357/580) with SFTS upon admission, and 68.4% patients (397/580) developed an abnormal TnI level during hospitalization. Multivariate logistic regression identified age, viral load, platelet count, creatinine level, and TnI level as potential risk factors for mortality in patients with SFTS. The results of restricted cubic splines revealed that when the TnI level (baseline TnI: 1.55 [lg (ng/L+1)], peak value: TnI 1.90 [lg (ng/L+1)]) exceeded a certain threshold, the predicted mortality of patients with SFTS increased alongside the rise in TnI levels. Mortality rate surpassed 40% among patients with SFTS with TnI greater than or equal to 10 times the upper limit of normal at admission (43.8%) or during hospitalization (41.7%). Older age, a history of cardiovascular disease, and higher d -dimer levels were potential risk factors for elevated TnI levels in patients with SFTS. Elevated TnI levels were prevalent among patients with SFTS and were strongly associated with an increased risk of mortality.

Predicting troponin biomarker elevation from electrocardiograms using a deep neural network.

Elevated troponin levels are a sensitive biomarker for cardiac injury. The quick and reliable prediction of troponin elevation for patients with chest pain from readily available ECGs may pose a valuable time-saving diagnostic tool during decision-making concerning this patient population. The data used included 15 856 ECGs from patients presenting to the emergency rooms with chest pain or dyspnoea at two centres in Sweden from 2015 to June 2023. All patients had high-sensitivity troponin test results within 6 hours after 12-lead ECG. Both troponin I (TnI) and TnT were used, with biomarker-specific cut-offs and sex-specific cut-offs for TnI. On this dataset, a residual convolutional neural network (ResNet) was trained 10 times, each on a unique split of the data. The final model achieved an average area under the curve for the receiver operating characteristic curve of 0.7717 (95% CI±0.0052), calibration curve analysis revealed a mean slope of 1.243 (95% CI±0.075) and intercept of -0.073 (95% CI±0.034), indicating a good correlation between prediction and ground truth. Post-classification, tuned for F1 score, accuracy was 71.43% (95% CI±1.28), with an F1 score of 0.5642 (95% CI±0.0052) and a negative predictive value of 0.8660 (95% CI±0.0048), respectively. The ResNet displayed comparable or surpassing metrics to prior presented models. The model exhibited clinically meaningful performance, notably its high negative predictive accuracy. Therefore, clinical use of comparable neural networks in first-line, quick-response triage of patients with chest pain or dyspnoea appears as a valuable option in future medical practice.

Use of cardiac biomarkers to improve initiation of cardioprotective therapy in patients with breast cancer receiving cardiotoxic chemotherapy in a multidisciplinary cancer center.

344 Background: Treatment for breast cancer commonly includes anthracyclines and anti-Her2 directed therapy, both of which carry a known cardiovascular risk. In high-risk patients, ESMO guidelines recommend consideration of cardiac biomarker (hs-cardiac troponin) testing for patients undergoing potentially cardiotoxic chemotherapy. Prophylactic use of cardioprotective medications such as angiotensin converting enzyme (ACE) inhibitors, angiotensin renin blockers (ARBs) or beta-blockers (BBs) can be considered to reduce development of cardiotoxicity. We aimed to identify the rates of cardiac biomarker testing performed and rates of abnormalities in patients considered to be high risk for cardiovascular disease undergoing breast cancer treatment with potentially cardiotoxic medication in hope of improving prevention efforts. Methods: We performed a retrospective chart review of patients with breast cancer treated with either anthracycline or anti-Her2 based therapy at our ambulatory cancer center from 2020 to 2023. Pre-treatment cardiovascular risk score was determined based on initial cardiac assessment at time of consultation with cardio-oncology. Completion of troponin biomarker testing and initiation of cardioprotective medication therapy was assessed. Patients who were not established with cardio-oncology or not on active cardiotoxic chemotherapy were excluded. Results: A total of 172 patients (66 on anthracycline based therapy and 106 on anti-HER2 therapy) were assessed. The average age of all patients was 57 years. 47 patients were assessed as high risk for cardiovascular disease. Of these high-risk patients, troponin was checked in 42 of 47 (89.4%) and found to be elevated in 23 of 42 (55%). Rate of troponin elevation was statistically significant for high risk patients compared to all other patients (p&lt;0.05). Cardioprotective medications were utilized in 28 of the 47 patients considered to be high risk (59.6%). Conclusions: In patients with breast cancer who require treatment with a potentially cardiotoxic medication, a clinical risk assessment with cardiology can be utilized to select those who may benefit from additional cardiac biomarker monitoring and potential earlier initiation of cardioprotective therapy. This single center study reveals that the use of clinical assessment of high vs low/medium risk allows us to predict patients with increased risk of cardiotoxicity. Our population had cardiac biomarkers checked in nearly all high-risk patients and troponin was elevated 55% of the time. Further study is needed to investigate if biomarker directed initiation of cardio-protective therapy could reduce cardio-toxicity.

Rapid Acute Coronary Syndrome Evaluation Over One Hour With High-Sensitivity Cardiac Troponin I: A United States-Based Stepped-Wedge, Randomized Trial

The real-world effectiveness and safety of a 0/1-hour accelerated protocol using high-sensitivity cardiac troponin (hs-cTn) to exclude myocardial infarction (MI) compared to routine care in the United States is uncertain. The objective was to compare a 0/1-hour accelerated protocol for evaluation of MI to a 0/3-hour standard care protocol. The RACE-IT trial was a stepped-wedge, randomized trial across 9 emergency departments (EDs) that enrolled 32,609 patientsevaluated for possible MI from July 2020 through April 2021. Patients undergoing high-sensitivity cardiac troponin I testing with concentrations less than or equal to 99th percentile were included. Patients who had MI excluded by the 0/1-hour protocol could be discharged from the ED. Patients in the standard care protocol had 0- and 3-hour troponin testing and application of a modified HEART score to be eligible for discharge. The primary endpoint was the proportion of patients discharged from the ED without 30-day death or MI. There were 13,505 and 19,104 patients evaluated in the standard care and accelerated protocol groups, respectively, of whom 19,152 (58.7%) were discharged directly from the ED. There was no significant difference in safe discharges between standard care and the accelerated protocol (59.5% vs 57.8%; adjusted odds ratio (aOR)=1.05, 95% confidence interval [CI] 0.95 to 1.16). At 30 days, there were 90 deaths or MIs with 38 (0.4%) in the standard care group and 52 (0.4%) in the accelerated protocol group (aOR=0.84, 95% CI 0.43 to 1.68). A 0/1-hour accelerated protocol using high-sensitivity cardiac troponin I did not lead to more safe ED discharges compared with standard care.

The therapeutic potential of red beetroot (Beta vulgaris L.) intake on muscle atrophy in immobilized mouse skeletal muscles

AbstractSkeletal muscle atrophy is the reduction in muscle mass and function caused by an imbalance in protein synthesis and degradation. Inflammation has been shown to accelerate protein degradation during periods of muscle inactivity. We investigated the potential therapeutic effects of beetroot extract (BRE) in reducing inflammation and oxidative stress to prevent muscular atrophy after a short period of immobilization. We divided 36 male BALB/c mice into three groups: control, muscular atrophy mice, and muscular atrophy mice treated with BRE (n = 12). Each group was further divided into two subgroups: (1) 7‐day immobilization and (2) 10‐day recovery. BRE was administered orally at a dose of 300 mg/kg for 17 days. We assessed the anti‐inflammatory and antioxidative effects of BRE using ELISA and RT‐PCR assays. Hematoxylin–eosin staining was used to measure the cross‐sectional area (CSA) of muscle fibers, and grip strength tests were performed to assess muscle strength. BRE administration increased muscle weight, CSA, and grip strength in mice with immobilization‐induced muscle atrophy. It also suppressed inflammation and oxidative stress biomarkers in atrophic muscle fibers. Higher nitrate levels and lower Troponin I (TnI) concentrations were observed in the BRE‐treated group, indicating improved muscle function and structure. These findings suggest that BRE may have therapeutic benefits in improving muscle mass and function and warrant further studies in humans, particularly in individuals with low physical activity levels.

Associations of Hypertension and Orthostatic Hypotension With Subclinical Cardiovascular Disease.

Orthostatic hypotension is associated with cardiovascular disease. It remains unclear if low standing blood pressure or high seated blood pressure is responsible for this association. We compared associations of orthostatic hypotension and hypertension with high-sensitivity cardiac troponin I and N-terminal pro-B-type natriuretic peptide. We performed a secondary analysis of the Study to Understand Fall Reduction and Vitamin D in You, a randomized controlled trial funded by the National Institute on Aging, between July 2015 and May 2019. Participants were community-dwelling adults, 70 years or older. Blood tests for high-sensitivity cardiac troponin I and N-terminal pro-B-type natriuretic peptide were drawn at visits concurrent with blood pressure measurements. Secondary analysis occurred in 2023. We determined associations between blood pressure phenotypes and cardiac biomarkers. Of 674 participants (mean age 76.5 ± 5.4 years, 43% female, 17.2% Black race), 29.1% had prior cardiovascular disease. Participants with seated hypertension had 10.1% greater high-sensitivity cardiac troponin I (95% confidence interval = 3.8-16.9) and 11.0% greater N-terminal pro-B-type natriuretic peptide (4.0-18.6) than those without seated hypertension. Participants with standing hypertension had 8.6% (2.7-14.9) greater high-sensitivity cardiac troponin I and 11.8% greater N-terminal pro-B-type natriuretic peptide (5.1-18.9) than those without standing hypertension. Hypotensive phenotypes were not associated with either biomarker. Both seated and standing hypertension were associated with greater high-sensitivity cardiac troponin I and N-terminal pro-B-type natriuretic peptide, but hypotensive phenotypes were not. Hypoperfusion may not be the principal mechanism behind subclinical cardiac injury among older adults with orthostatic hypotension.

Relevance of surveillance manual for the early detection of immune checkpoint inhibitor-induced myocarditis: A case series

ObjectiveThe European Cardio-Oncology Guidelines recommend regular electrocardiography and troponin testing during immune checkpoint inhibitors (ICIs) treatment, but their efficacy for monitoring ICI treatment remains unclear. This study aimed to evaluate the effectiveness of a surveillance protocol for early detection of ICI-induced myocarditis. MethodsBetween May 2014 and May 2024, patients who began treatment with ICIs at our hospital and developed ICI-induced myocarditis were included in this study. We created a straightforward management flowchart for myocarditis. The protocol was based on monitoring troponin T levels. We confirmed the efficacy of our surveillance protocol using a case series of ICI-induced myocarditis. ResultsDuring the observation period, 3481 patients were newly started on ICIs at our hospital. Five patients were previously diagnosed with myocarditis, and five patients were diagnosed with myocarditis after the implementation of the surveillance protocol. The manual enabled the early detection of myocarditis, and the mortality rate for myocarditis at our hospital improved from 60% to 0%. The incidence of conduction system disorders significantly reduced from 100% to 0% (P ​< ​0.01). After the surveillance protocol was initiated, there were no cases of myocarditis requiring immunosuppressive drugs beyond steroids. ConclusionsThis study confirmed the relevance of a troponin-based surveillance protocol for the early detection of ICI-induced myocarditis. The implementation of the surveillance protocol reduced mortality from myocarditis and significantly reduced serious complications of conduction system disorders. Although this study is a small case series of patients who developed myocarditis, we confirm the effectiveness of surveillance for myocarditis.

Implementation of a High-sensitivity Troponin Assay for Adult Patients Who Present to the Emergency Department: The Role of Clinical Decision Support

BackgroundThe objective of this study was to assess the health outcomes for patients who present to the emergency department (ED) with cardiac chest pain after the implementation of an accelerated diagnostic protocol using a high-sensitivity troponin assay (hs-TnI). MethodsThis prospective before-after cohort study used population-based linked health administrative data for adult patients who presented to a Canadian urban ED with chest pain of suspected cardiac origin over a 2-year study period. The primary outcome was ED length of stay (LOS). Secondary outcomes included operational and clinical outcomes within 30 days of the index ED visit. ResultsDuring the study period, 4339 patients were included, with 2031 in the conventional troponin group and 2308 in the hs-TnI group. Overall, the median age was 56 years and 52% were male. The median ED LOS was reduced from 430 minutes to 400 minutes after protocol implementation (median difference, -30.0; 95% confidence interval, -47.8 to -12.3). For discharged patients who underwent serial troponin tests, the LOS was 89 minutes shorter (95% confidence interval, -110.8 to -67.2). The proportion of patients discharged increased from 73% to 78% after implementation (P = 0.0001). At 30 days, there were no differences in hospital readmission or major adverse event outcomes. ConclusionsUsing clinical decision support, the implementation of a new hs-TnI and accelerated diagnostic protocol was associated with shorter ED LOS and fewer hospitalizations for adult patients with chest pain who were assessed in the ED. These results suggest that the protocol is effective and safe in real-world clinical settings.

ST-Segment Alterations in the Electrocardiogram of Acute Pulmonary Thromboembolism: A Rabbit Model

In this study, we investigated the mechanism underlying electrocardiogram (ECG) alterations in a rabbit model of acute pulmonary thromboembolism (PTE). Twelve healthy adult New Zealand white rabbits were used, with eight in the experimental group (PTE group) and four in the control group. After developing the rabbit model of acute PTE, ECG and coronary angiography were performed. HE staining was conducted on the right and left ventricular tissues, and polymerase chain reaction (PCR) was used to determine brain natriuretic peptide (BNP), tumor necrosis factor-alpha (TNF-α), and Troponin I (TNI) mRNA expression in the myocardium. There were considerable changes in the ST segment of the ECG in the PTE group. Coronary angiography revealed the absence of spasm, stenosis, and occlusion. In the plasma of the PTE group, the levels of D-dimer, BNP, TNF-α, and TNI were significantly elevated, and these changes were statistically significant (P&lt;0.05). PCR analysis of ventricular myocardial tissue indicated significantly higher levels of BNP, TNF-α, and TNI mRNA in the PTE group than in the control group. These differences were statistically significant (P&lt;0.05). The ST-T variations on the ECG of rabbits with acute PTE correlate strongly with the temporary changes in right heart volume caused by acute PTE.

Influence of Anticoagulants on the Dissociation of Cardiac Troponin Complex in Blood Samples.

Immunodetection of cardiac isoforms of troponin I (cTnI) and troponin T (cTnT) in blood samples is widely used for the diagnosis of acute myocardial infarction. The cardiac troponin complex (ITC-complex), comprising cTnI, cTnT, and troponin C (TnC), makes up a large portion of troponins released into the bloodstream after the necrosis of cardiomyocytes. However, the stability of the ITC-complex has not been fully investigated. This study aimed to investigate the stability of the ITC-complex in blood samples. A native ITC-complex was incubated in buffer solutions, serum, and citrate, heparin, or EDTA plasma at various temperatures. Western blotting and gel filtration were performed, and troponins were detected using specific monoclonal antibodies. The ITC-complex dissociated at 37 °C in buffers with or without anticoagulants, in citrate, heparin, and EDTA plasmas, and in serum, into a binary cTnI-TnC complex (IC-complex) and free cTnT. In plasma containing heparin and EDTA, the IC-complex further dissociated into free TnC and cTnI. No dissociation was found at 4 °C or at room temperature (RT) in all matrices within 24 h except for EDTA plasma. After incubation at 37 °C in EDTA plasma and serum, dissociation was accompanied by proteolytic degradation of both cTnI and cTnT. The presence of anti-troponin autoantibodies in the sample impeded dissociation of the ITC-complex. The ITC-complex dissociates in vitro to form the IC-complex and free cTnT at 37 °C but is mostly stable at 4 °C or RT. Further dissociation of the IC-complex occurs at 37 °C in plasmas containing heparin and EDTA.

Utility of rest magnetocardiography in patients presenting to the emergency department with chest pain: A case series on the CardioFlux MCG

BackgroundMagnetocardiography (MCG) may provide a rapid diagnostic option for patients presenting with chest pain in the emergency department (ED). Case summariesThis case series presents two instances from a multicenter study, where MCG could have served as a rapid, non-invasive diagnostic tool for chest pain patients. In both cases, multiple high-sensitivity troponin (hsTn) tests yielded incorrect evidence of ischemia. In the first case, multiple positive hsTn tests led to the patient requiring 23 h of observation care, while MCG rapidly ruled out acute coronary syndrome (ACS). In the second case, MCG revealed findings indicative of cardiac ischemia where serial ECGs did not indicate ischemia and serial hsTns were normal. Subsequent cardiac catheterization confirmed 99 % stenosis in the patient's left main and left anterior descending arteries, necessitating coronary artery bypass grafting (CABG). ConclusionMCG offers a rapid, painless, non-invasive, radiation free assessment for patients presenting with acute chest pain. Integrating MCG into ED workflows has the potential to improve throughput, reduce the need for subsequent patient observation or inpatient admission, and minimize or eliminate the need for other more expensive non-invasive cardiac testing. MCG avoids some of the problems associated with other methods for diagnosing ischemia. MCG does not involve radiation or the use of pharmacologic agents which have a risk for allergic reactions and anaphylaxis, or the need for an intravenous line. Stress tests are frequently contraindicated or unable to be performed in patients on various medications, may require patient cooperation and in the case of exercise stress tests, the patient's capability to exercise. MCG requires no special patient preparation.

Identification of human metabolites of fast skeletal troponin activators Tirasemtiv and Reldesemtiv for doping control purposes.

The fast skeletal troponin activators (FSTAs) Reldesemtiv and Tirasemtiv were developed for patients suffering from neuro-degenerative diseases of the motor nervous system, e.g. amyotrophic lateral sclerosis (ALS). The drug candidates can increase the sensitivity of troponin C to calcium by selectively activating the troponin complex resulting in increased skeletal muscle contraction. Although the development of the drug candidates is currently discontinued because of missed end points in phase III clinical studies with patients with ALS, phase I clinical trials showed an increase in muscle contraction force in healthy humans. This effect could be abused by athletes to enhance performance in sports. As the substances are listed on the 2024 edition of the World Anti-Doping Agency's Prohibited List, the aim of this study was to identify and characterize metabolites of Reldesemtiv and Tirasemtiv to ensure their reliable identification in doping control analyses. The biotransformation of the drug candidates was studied in vitro using pooled human liver microsomes and 3D cultivated human hepatic cells of the cell line HepaRG, yielding a total of 11 metabolites of Reldesemtiv and eight of Tirasemtiv. In addition, a human elimination study was conducted to investigate the metabolism and elimination profile of Tirasemtiv and Reldesemtiv in vivo, suggesting the N-glucuronide of Tirasemtiv and hydroxylated 3-fluoro-2-(3-fluoro-1-methylcyclobutyl)pyridine as well as its glucuronide as suitable target analytes for routine doping controls. Applying a validating HPLC-MS/MS method, optimized to detect Reldesemtiv and Tirasemtiv in human urine, microdosing (50 μg) of each substance was traceable for 24-72 h.

Abstract Or103: Troponin I Serine 150 Phosphorylation as a Novel Cardiac Inotrope Without Detrimental Effects

Heart failure with systolic dysfunction is characterized by insufficient contractility. Standards of care for heart failure treat symptoms, however there are currently no approved therapies to increase contractility to directly improve the ability of the heart to pump blood. Previously tested positive inotropes increased heart function through mechanisms that increased intracellular calcium. Unfortunately, these early inotropes were associated with detrimental effects and worsened outcomes and therefore are not approved for long-term use. There remains a need for an alternative mechanism to increase contractility without increasing intracellular calcium. We previously demonstrated that phosphorylation of the inhibitory subunit of the troponin complex, troponin I (TnI) at serine residue 150 (S150) increases force development in ex vivo muscle by increasing calcium sensitivity. Increasing the sensitivity of the myofilament to calcium is an alternative mechanism to increase contractility without increasing intracellular calcium. We therefore hypothesize that increasing TnI-S150 phosphorylation in vivo would improve systolic function without harmful effects. To determine the effects of TnI-S150 phosphorylation in vivo , we generated a phosphorylation-mimetic mouse with TnI-S150 mutated to aspartic acid (TnI-pS150). Structural and functional measurements derived from echocardiography and hemodynamics demonstrate that TnI-pS150 mice have increased cardiac systolic function and contractility in vivo . We confirm that the mechanism for increasing in vivo function is through increased myofilament calcium sensitivity. Detrimental effects commonly observed with the use of inotropes (e.g. hypertrophy, hypertension, severe diastolic dysfunction, increased arrythmia susceptibility, increased mortality) were not observed in TnI-pS150 mice. Additionally, we did not observe any adverse long-term detrimental effects on cardiac structure and function in aged TnI-pS150 mice. These results support the phosphorylation of TnI-S150 as a novel signaling mechanism to increase systolic function without detrimental effects and is therefore a novel target for systolic heart failure therapies.

Abstract Mo028: Persistence of Fetal Cardiac Troponin T Modulates Disease Severity in Anthracycline-Induced Cardiomyopathy

Anthracyclines are a key component in the management of pediatric cancers long recognized to carry significant risk of dose-dependent cardiotoxicity. Despite advancements in clinical management, considerable variation in the incidence of cardiotoxicity persists across dosing regimens suggesting modifiers exist. Recently, changes in the splicing of TNNT2, the gene encoding cardiac troponin T (cTnT), were postulated to contribute to anthracycline cardiotoxicity, potentially providing a direct link to the myofilament. Previous studies in our lab have demonstrated that the fetal isoform, cTnT1, is a potent modifier of cardiac function contributing to disease heterogeneity in animal models of cardiomyopathies. Thus, we hypothesize that the persistent expression of cTnT1 predisposes a subset of the population to anthracycline cardiomyopathy. Using molecular dynamics simulations (MD) and isothermal titration calorimetry (ITC), we assessed a range of anthracyclines for their potential to bind the cardiac thin filament (CTF). MD calculated Glide scores showed direct binding to the troponin complex. ITC indicated that this binding occurs at an order of magnitude higher affinity in complexes containing cTnT1. Stopped-flow kinetics of cTnT1 CTFs exposed to Doxorubicin showed an additive reduction in calcium dissociation rates, reinforcing our observations of direct binding to the CTF. Longitudinal 2D echocardiography of Doxorubicin treated mice (3mg/kg/week) indicated that both male and female cTnT1 mice exhibit an additive, dose-dependent reduction in cardiac systolic function compared to non-transgenic (NT) littermates. Consistent with clinical data, female mice exhibited an earlier reduction in % fractional shortening than males as well as delayed recovery after treatment cessation. Transcriptional profiling of mice treated with Doxorubicin revealed a 2- to 7-fold additive increase in type I and type II interferon signaling in cTnT1 mice above that observed in treated NT littermates. These data suggest that cTnT1 may increase binding of anthracyclines at the myofilament, eliciting accelerated cardiac dysfunction, and represent a unique, targetable genetic risk factor involved in anthracycline cardiotoxicity.

Utility of serial troponin testing for emergency department patients with syncope.

For emergency department (ED) patients with syncope, cardiac troponin can identify acute coronary syndrome (ACS) and prognosticate for 30-day serious adverse events. However, it is unclear if serial testing improves diagnostic yield and prognostication. This was a secondary analysis of data from two prospective studies conducted to develop the Canadian Syncope Risk Score. Adults (age ≥ 16 years) with syncope were enrolled, and patient characteristics, vital signs, physician diagnostic impression, electrocardiogram and troponin results, and adjudicated 30-day serious adverse event were collected. The primary outcome was the detection of a serious adverse event within 30 days of ED disposition. The secondary outcome was comparison of ED length of stay among patients with single versus serial troponin measurements. 4996 patients [mean age 64.5 (SD 18.8) years, 52.2% male] were included: 4397 (89.8%) with single troponin [232 (5.3%) with serious adverse event in the ED and 203 (4.6%) after ED disposition]; 499 (10.2%) patients with > 1 troponin measurement [39 (7.8%) with serious adverse event in ED and 60 (12.0%) after ED disposition]. Among those with serial measurements, 10 patients (2.0%) had a rise from below to above the 99th percentile threshold, of whom 4 patients (0.8%) suffered serious adverse event: two with arrhythmias diagnosed on electrocardiogram, one with ACS and one suffered respiratory failure. Nine patients (1.8%) had Canadian Syncope Risk Score risk reclassification based on serial measurement, and none suffered 30-day serious adverse event. Median ED length of stay was significantly longer for patients with serial testing (5.6 vs. 3.8 h, p < 0.001). The initial troponin measurement was sufficient for serious adverse event detection and in-ED risk stratification. Serial troponin testing does not improve the diagnostic yield or prognostication and should be reserved for patients with ongoing symptoms or electrocardiogram findings suggestive of cardiac ischemia.

A multiple criteria decision analysis to establish the use cases and candidate point of care tests to enter into a platform trial of multiple in vitro diagnostic point of care tests in the prehospital environment.

There are increasing demands on Emergency Medical Services. More efficient treatment pathways are required to support conveyance decision making and patient referral in prehospital care. Point of Care testing is increasingly available and utilised across the NHS to support optimal ways of working. We aimed to design and conduct a Multiple Criteria Decision Analysis to prioritise in vitro point of care tests and use cases for inclusion in a platform trial of in vitro point of care testing in UK Emergency Medical Services. We designed a Multiple Criteria Decision Analysis that included systematic scoping reviews stakeholder recruitment, two stakeholder surveys and two stakeholder workshops to scope the use cases, explore criteria and map use cases, evaluate the criteria and measure the use cases against the criteria. We recruited 32 stakeholders. We developed a scoring matrix with 4 criteria for scoring the use cases and 8 criteria for scoring the point of care tests and applied weighting determined from survey results. Use cases were scored by the stakeholders against 4 criteria. The 3 highest scoring use cases were point of care troponin testing in: possible Acute Myocardial Infarction, lactate testing in suspected sepsis and in trauma. We developed the process for scoring the point of care tests to be completed close to a proposed trial to allow for a changes in technology. We successfully designed a Multiple Criteria Decision Analysis to identify use cases and candidate tests for inclusion in a future platform trial of in vitro point of care testing in UK Emergency Medical Services. We identified 3 use cases for evaluation in a platform trial of in vitro point of care testing: troponin testing in possible acute myocardial infarction, lactate testing in suspected sepsis and lactate testing to identify occult haemorrhage in trauma.