Detectable troponin below the 99th percentile predicts survival in patients undergoing coronary angiography.

Background: Cardiac troponin I (cTnI) above the 99th percentile is associated with an increased risk of major adverse events. Patients with detectable cTnI below the 99th percentile are a heterogeneous group with a less well-defined risk profile. The purpose of this study is to investigate the prognostic relevance of detectable cTnI below the 99th percentile in patients undergoing coronary angiography. Methods: The study included 14,776 consecutive patients (mean age of 65.4 ± 12.7 years, 71.3 % male) from the Essen Coronary Artery Disease (ECAD) registry. Patients with cTnI levels above the 99th percentile and patients with ST-segment elevation acute myocardial infarction were excluded. All-cause mortality was defined as the primary endpoint. Results: Detectable cTnI below the 99th percentile was present in 2811 (19.0 %) patients, while 11,965 (81.0 %) patients were below detection limit of the employed assay. The mean follow-up was 4.25 ± 3.76 years. All-cause mortality was 20.8 % for patients with detectable cTnI below the 99th percentile and 15.0 % for those without detectable cTnI. In a multivariable Cox regression analysis, detectable cTnI was independently associated with all-cause mortality with a hazard ratio of 1.60 (95 % CI 1.45-1.76; p < 0.001). There was a stepwise relationship with increasing all-cause mortality and tertiles of detectable cTnI levels with hazard ratios of 1.63 (95 % CI 1.39-1.90) for the first tertile to 2.02 (95 % CI 1.74-2.35) for the third tertile. Conclusions: Detectable cTnI below the 99th percentile is an independent predictor of mortality in patients undergoing coronary angiography with the risk of death growing progressively with increasing troponin levels.

Noninvasive cardiac-specific biomarkers for the diagnosis and prevention of vascular stenosis in cardiovascular disorder.

Background: The most frequent lesion in the blood vessels feeding the myocardium is vascular stenosis, a condition that develops slowly but can prove to be deadly in a long run. Non-invasive biomarkers could play a significant role in timely diagnosis, detection and management for vascular stenosis events associated with cardiovascular disorders. Aims: The study aimed to investigate high sensitivity troponin I (hs-TnI), cardiac troponin I (c-TnI) and high sensitivity C-reactive protein (hs-CRP) that may be used solely or in combination in detecting the extent of vascular stenosis in CVD patients. Methodology: 274 patients with dyspnea/orthopnea complaints visiting the cardiologists were enrolled in this study. Angiographic study was conducted on the enrolled patients to examine the extent of stenosis in the five prominent vessels (LDA, LCX, PDA/PLV, RCA, and OM) connected to the myocardium. Samples from all the cases suspected to be having coronary artery stenosis were collected, and subjected to biochemical evaluation of certain cardiac inflammatory biomarkers (c-TnI, hsTn-I and hs-CRP) to check their sensitivity with the level of vascular stenosis. The extent of mild and culprit stenosis was detected during angiographic examination and the same was reported in the form significant (≥50% stenosis in the vessels) and non-significant (<50% stenosis in the vessels) Carotid Stenosis. Ethical Clearance for the study was provided by Dr. Ram Manohar Lohia Institute of Medical Sciences Institutional Ethical Committee. Informed consent was obtained from all the participants enrolled in the study. Results: We observed that 85% of the total population enrolled in this study was suffering from hypertension followed by 62.40% detected with sporadic episodes of chest pain. Most of the subjects (42% of the total population) had stenosis in their LAD followed by 38% who had stenosis in their RCA. Almost 23% patients were reported to have stenosis in their LCX followed by OM (18% patients), PDA/PLV (13%) and only 10% patients had blockage problem in their diagonal. 24% of the subjects were found to have stenosis in a single vessel and hence were categorized in the Single Vessel Disease (SVD) group while 76% were having stenosis in two or more than two arteries (Multiple Vessel Disease). hs-TnI level was found to be correlated with the levels of stenosis and was higher in the MVD group as compared to the SVD group. Conclusion: hs-TnI could be used as a novel marker as it shows prominence in detecting the level of stenosis quite earlier as compared to c-TnI which gets detected only after a long duration in the CVD patients admitted for angiography. hs- CRP gets readily detected as inflammation marker in these patients and hence could be used in combination with hs-TnI to detect the risk of developing coronary artery disease.

A Case of Reverse Takotsubo Cardiomyopathy After Administering a Local Anesthetic Containing Epinephrine.

Takotsubo cardiomyopathy (TCM) is a rare syndrome characterized by acute and transient distinctive wall motion abnormalities accompanied by other defined objective findings. There are many variants of TCM, including the reverse (or basal) subtype. While the pathogenesis is not fully understood, both endogenous and exogenous catecholamines have been implicated. This case report describes a 30-year-old active-duty military female who developed reverse TCM immediately following local anesthetic with epinephrine administration in preparation for an elective septorhinoplasty. She developed electrocardiogram (ECG) changes, temporary hemodynamic instability, and cardiac troponin elevation. Transthoracic echocardiogram (TTE) demonstrated significantly reduced systolic and diastolic function, with akinesis of the basal segments and normal wall motion of the apical segments, consistent with a reverse Takotsubo pattern. Coronary computed tomography (CT) angiography showed normal coronary arteries. Repeat TTE was performed two days after the initial event and showed near-complete resolution of the wall motion abnormalities. Fourteen days later, TTE showed normalization of cardiac function. While there is a favorable prognosis for most patients with this diagnosis, there does remain the potential for significant adverse outcomes, risk of recurrence, and a non-negligible mortality rate. It is widely known that physical and emotional triggers can precipitate TCM through the release of catecholamines. This case, in addition to numerous other case reports, provides further documentation and support that exogenous epinephrine administration is also associated with the development of TCM. Clinicians should consider the diagnosis of Takotsubo cardiomyopathy if hemodynamic or ECG changes arise following epinephrine administration.

Exercise-induced cardiac troponin elevations and cardiac ventricular dysfunction assessed by tissue Doppler echocardiography and speckle tracking among non-elite runners in Beijing marathon.

OBJECTIVES: We aimed to identify the major determinants of cardiac troponin changes response to exercise among non-elite runners participating in the Beijing 2022 marathon, with a particular focus on the associations with the cardiac function assessed by tissue Doppler echocardiography and speckle tracking. DESIGN: A prospective study. METHODS: A total of 33 non-elite participants in the 2022 Beijing Marathon were included in the study. Echocardiographic assessment and blood sample collection were conducted before, immediately after, and two weeks after the marathon. Blood samples were analyzed using the same Abbot high-sensitivity cTnI STAT assay. Echocardiography included tissue Doppler and speckle tracking echocardiography. RESULTS: Following the marathon, significant increases were observed in cardiac biomarkers, with hs-cTnI elevating from 3.1 [2.3-6.7] to 49.6 [32.5-76.9] ng/L (P < 0.0001). Over 72 % of participants had post-race hs-TnI levels surpassing the 99th percentile upper reference limit. There was a notable correlation between pre-marathon hs-cTnI levels (ß coefficient, 0.56 [0.05, 1.07]; P = 0.042), weekly average training (ß coefficient, -1.15 [-1.95, -0.35]; P = 0.009), and hs-cTnI rise post-marathon. Echocardiography revealed significant post-race cardiac function changes, including decreased E/A ratio (P < 0.0001), GWI (P < 0.0001), and GCW (P < 0.0001), with LVEF (ß coefficients, 0.112 [0.01, 0.21]; P = 0.042) and RV GLS (ß coefficients, 0.124 [0.01, 0.23]; P = 0.035) changes significantly associated with hs-TnI alterations. All echocardiographic and laboratory indicators reverted to baseline levels within two weeks. CONCLUSIONS: Baseline hs-cTnI levels and weekly average training influence exercise-induced hs-cTnI elevation in non-elite runners. Echocardiography revealed post-race changes in cardiac function, with LVEF and RV GLS significantly associated with hs-TnI alterations. These findings contribute to understanding the cardiac response to exercise and could guide training and recovery strategies.

Clinical Implications of High-Sensitivity Troponin Elevation Levels in Non-ST-Segment Elevation Myocardial Infarction Patients: Beyond Diagnostics.

Standard troponin has long been pivotal in diagnosing coronary syndrome, especially Non-ST-Segment Elevation Myocardial Infarction (NSTEMI). The recent introduction of high-sensitivity troponin (hs-cTnI) has elevated it to the gold standard. Yet, its nuanced role in predicting angiographic lesions and clinical outcomes, notably in specific populations like obesity, remains underexplored. Aim: To evaluate the association between hs-cTnI magnitude in NSTEMI patients and angiographic findings, progression to acute heart failure, and its performance in obesity. Methods: Retrospective study of 208 NSTEMI patients at a large university center (2020-2023). Hs-cTnI values were assessed for angiographic severity, acute heart failure, and characteristics in the obese population. Data collected and diagnostic performance were evaluated using manufacturer-specified cutoffs. Results: 97.12% of patients had a single culprit vessel. Hs-cTnI elevation correlated with angiographic stenosis severity. Performance for detecting severe coronary disease was low, with no improvement using a higher cutoff. No association was found between hs-cTnI and the culprit vessel location. Hs-cTnI did not predict acute heart failure progression. In the obese population, hs-cTnI levels were higher, but acute heart failure occurred less frequently than in non-obese counterparts. Conclusions: In NSTEMI, hs-cTnI elevation is associated with significant stenosis, but not with location or acute heart failure. Obesity correlates with higher hs-cTnI levels but a reduced risk of acute heart failure during NSTEMI.

Markedly elevated high-sensitivity troponin and in-hospital mortality after cardiac surgery.

BACKGROUND: High-sensitivity troponin (hsTnI) is correlated with cardiac mortality; however, studies on the relationship of markedly elevated hsTnI with in-hospital mortality after cardiac surgery are sparse. Therefore, we aimed to define this relationship in order to help guide in-hospital, acute management of post-surgical patients. METHODS: We retrospectively analyzed all cardiac surgeries completed at our institution between January 2020 and June 2022 in which a peak hsTnI was noted to be >35× upper limit of normal (ULN = 34 ng/L). The primary outcome was in-hospital death. Subgroup analysis was performed to assess differences between coronary artery bypass grafting (CABG) and other cardiac surgeries. RESULTS: A total of 1382 cases met inclusion criteria. The patients' mean age was 64.8 years and 68.2 % were male. Median peak hsTnI after surgery was 4202 ng/L (interquartile ratio: 2427-7654). Univariate analysis of troponin level with mortality found that for every 1000 ng/L increase in hsTnI, odds of in-hospital death increased by 3.8 % (odds ratio [OR]: 1.038; 95 % confidence interval [CI] 1.027-1.050; p < 0.0001). In a multivariate model, troponin (OR 1.02; 95 % CI 1.01-1.04; p = 0.004) maintained a significant association with in-hospital death. CABG was associated with a lower risk of in-hospital death for any given hsTnI level up to 60,000 ng/L compared to other cardiac surgeries. CONCLUSION: Increasing hsTnI level is associated with increasing probability of in-hospital mortality and, therefore, serves as an additional, objective measure of risk to help guide in-hospital clinical management.

SARS-CoV-2 Infection-Dependent Modulation in Vital Components of the Serum Profile of Severely SARS-CoV-2 Infected Patients.

Background: COVID-19 modulates many serological biomarkers during the progress of disease severity. The study aimed to determine COVID-19 severity-associated perturbance in the serum profile. Methods: A retrospective study including COVID-19-positive individuals (n = 405) was accomplished. The serum profile of COVID-19 participants was mined from laboratory records. Severity-associated alteration in the serum profile was evaluated using Pearson correlation, regression, VCramer, Bayesian posterior VCramer, and bias factor using R-base-RStudio-version-3.3.0 with a significant cut-off of p < 0.05. Results: Significantly different mean ± standard deviation (SD) (highly versus moderately severe) of C-reactive protein (CRP), ferritin, neutrophil-lymphocyte ratio (NLR), D-dimer, platelets, prothrombin time (PT), partial prothrombin time (PTT), troponin 1, lactate dehydrogenase (LDH), aspartate-aminotransferase (AST), alanine aminotransferase (ALT), and AST/ALT ratio was observed (p < 0.001). Highly severe COVID-19 associated with CRP, ferritin, NLR, in D-dimer, PT, PTT, troponin 1, AST/ALT ratio, AST and ALT (adjusted odds ratio (AOR): 1.346, 1.05, 1.46, 1.33, 1.42, 1.23, 4.07, 3.9, 1.24, 1.45, p < 0.001). CRP with ferritin (r = 0.743), NLR (r = 0.77), white blood cells (WBC) (r = 0.8), troponin1 with LDH (r = 0.757), and D-dimer with platelets (r = -0.81) were highly correlated. X2pearson (p < 0.001), VCramer (0.71), Bayesian-VCramer (0.7), and bias-factor (-125) for troponin 1 indicate the strong association of troponin 1 level and with COVID-19 severity. X2pearson (p < 0.001), VCramer (1), Bayesian-VCramer (0.98), and bias-factor (-266.3) for NLR exhibited a very strong association of pathologic conditions with the high severity of the disease. Conclusion: These biomarkers of inflammation (CRP, Ferritin, NLR), coagulation disorders (D-dimer, PT, and PTT) cardiac abnormality (troponin 1), and liver injury (AST/ALT) could be crucial in low-medical resource settings as potential prognosticator/predictors of the COVID-19 severity and clinical outcomes. Moreover, the outcome of this study could be leveraged for the early prediction of disease severity during SARS-CoV or Middle East Respiratory Coronavirus (MERS-CoV) infection.

A universal strategy for constructing high-performance silica-based AIE materials for biomedical application.

As an emerging fluorophore, aggregation-induced emission luminogens (AIEgens) have received widespread attention in recent years, but the inherent drawbacks of AIEgens, such as the poor water-solubility and insufficient fluorescence stability in complex environments, restrict their performance in practical applications. Herein, we report a universal strategy based on hydrophobic dendritic mesoporous silica (HMSN) that can integrate different AIE molecules to construct multi-color fluorescent AIE materials. Specifically, HMSN with central radial pores was used as a powerful carrier for direct loading AIE molecules and restricting their intramolecular motions. Due to the pore-domain restriction effect and hydrophobic interaction, the obtained silica-based AIE materials have bright fluorescence with a maximum quantum yield of 68.38%, high colloidal/fluorescence stability, and excellent biosafety. Further, these silica-based AIE materials can be conjugated with functional antibodies to obtain probes with different targetability. After integration with immunomagnetic beads, the prepared detection probes achieved the quantitative detection of cardiac troponin I with the limit of detection (LOD) of 0.508 ng/mL. Overall, the targeting probes stemming from silica-based AIE materials can not only achieve cell-specific imaging, but quantify the number of Jurkat cells (LOD = 270 cells/mL) to further determine the specific etiology of the disease.

Prognostic Value and Determinants of High-Sensitivity Cardiac Troponin T in Patients With a Systemic Right Ventricle: Insights From the SERVE Trial.

BACKGROUND: The determinants and prognostic value of high-sensitivity cardiac troponin T (hs-cTnT) among patients with a systemic right ventricle are largely unknown. METHODS AND RESULTS: Ninety-eight patients from the randomized controlled SERVE (Effect of Phosphodiesterase-5 Inhibition With Tadalafil on Systemic Right Ventricular Size and Function) trial were included. The correlation between baseline hs-cTnT concentrations and biventricular volumes and function quantified by cardiac magnetic resonance or cardiac multirow detector computed tomography was assessed by adjusted linear regression models. The prognostic value of hs-cTnT was assessed by adjusted Cox proportional hazards models, survival analysis, and concordance statistics. The primary outcome was time to the composite of clinically relevant arrhythmia, hospitalization for heart failure, or all-cause death. Median age was 39 (interquartile range, 32-48) years, and 32% were women. Median hs-cTnT concentration was 7 (interquartile range, 4-11) ng/L. Coefficients of determination for the relationship between hs-cTnT concentrations and right ventricular end-systolic volume index and right ventricular ejection fraction (RVEF) were +0.368 (P=0.046) and -0.381 (P=0.018), respectively. The sex- and age-adjusted hazard ratio for the primary outcome of hs-cTnT at 2 and 4 times the reference level (5 ng/L) were 2.89 (95% CI, 1.14-7.29) and 4.42 (95% CI, 1.21-16.15), respectively. The prognostic performance quantified by the concordance statistics for age- and sex-adjusted models based on hs-cTnT, right ventricular ejection fraction, and peak oxygen uptake predicted were comparable: 0.71% (95% CI, 0.61-0.82), 0.72% (95% CI, 0.59-0.84), and 0.71% (95% CI, 0.59-0.83), respectively. CONCLUSIONS: Hs-cTnT concentration was significantly correlated with right ventricular ejection fraction and right ventricular end-systolic volume index in patients with a systemic right ventricle. The prognostic accuracy of hs-cTnT was comparable to that of right ventricular ejection fraction and peak oxygen uptake predicted. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03049540.

Modeling the Impact of Biomarker-Guided Versus ASCVD Risk-Guided Drug Treatment in US Adults With Stage 1 Hypertension: The National Health and Nutrition Examination Survey, 1999 to 2004.

BACKGROUND: Guidelines recommend antihypertensive medication for adults with both stage 1 hypertension (systolic blood pressure, 130-139 mm Hg or diastolic blood pressure, 80-89 mm Hg) and 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥10%. Cardiac biomarkers could facilitate a more targeted approach to the treatment of stage 1 hypertension. METHODS: We studied 1999 to 2004 National Health and Nutrition Examination Survey participants aged ≥20 years with untreated stage 1 hypertension without heart failure or ASCVD. hs-cTnI (high-sensitivity cardiac troponin I) and hs-cTnT (high-sensitivity cardiac troponin T) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) were measured in stored serum. We used the Pooled Cohort Equations to predict 10-year ASCVD risk. All participants had linked mortality follow-up through December 31, 2019. RESULTS: Overall, 17.5% of US adults (32.2 million) had untreated stage 1 hypertension. Among these 32.2 million persons, 15.7% had ASCVD risk ≥10%, 5.6% had elevated hs-cTnI, 4.7% had elevated hs-cTnT, and 9.5% had elevated NT-proBNP. Among adults aged 65 to 79 years with untreated stage 1 hypertension, 80.5% had ASCVD risk ≥10%, 13.0% had elevated hs-cTnI, 15.2% had elevated hs-cTnT, and 29.4% had elevated NT-proBNP. Less than half of the adults aged ≥80 years with untreated stage 1 hypertension had elevated biomarkers. The cardiovascular disease mortality rates among all adults with untreated stage 1 hypertension and with either ASCVD risk ≥10%, elevated hs-cTnI, elevated hs-cTnT, or elevated NT-proBNP were 7.51, 7.74, 8.75, and 5.87 per 1000 person-years, respectively. CONCLUSIONS: Cardiac biomarkers may be more selective for informing risk-based treatment decisions in stage 1 hypertension, particularly among adults aged ≥65 years.

Macrotroponin in the COVID-19 Era: An Under-Recognised Cause of Persistent Troponin Elevation.

Troponin is an important diagnostic tool, however, as the assay sensitivity and frequency of testing has increased in the COVID-19 era, a new cohort of patients with persistently elevated troponin has emerged. Interfering antibodies should be considered in patients with persistent and stable troponin elevation, where there is no ongoing cause.

Validation of Becton Dickinson Barricor™ tubes for use with Abbott Alinity™ and Siemens Atellica® highly sensitive cardiac troponin I measuring systems.

BACKGROUND: BD Barricor™ tubes have been proposed to decrease laboratory turnaround time (TAT). We analytically validated and then clinically verified these tubes for use with Abbott Alinity™ and Siemens Atellica® highly sensitive cardiac troponin I (hs-cTnI) assays. METHODS: hs-cTnI measurements were undertaken in paired Barricor™ and in-use PSTII™ tubes on both systems. 359 matched samples with hs-cTnI levels between 3 and 15,000 ng/L (Atellica® values) were used to assess the hemolysis rate and make method comparisons. 599 paired patient samples were collected on emergency department (ED) admission to compare the performance of the rapid acute myocardial infarction (AMI) rule-out strategy based on hs-cTnI concentrations lower than recommended thresholds (<4 ng/L Alinity™; <5 ng/L Atellica®) when different tubes and systems were employed. RESULTS: No between-tube differences in hemolysis rate were seen when free hemoglobin concentrations in plasma samples were ≥0.25 g/L, even if PSTII™ showed a significant increase of hemolysis rate vs. Barricor™ (31% vs. 22%, p=0.007) when a lower cut-off for hemolysis (≥0.11 g/L) was employed on the Atellica® detection system. The alternate use of these tubes did not influence the hs-cTnI results obtained from either of the two assays, which remained markedly biased (~40%) irrespective of the tube used. The expected optimal ability of very low hs-cTnI values on ED admission for ruling out AMI was confirmed by using both systems regardless of the tube type. CONCLUSIONS: Barricor™ and PSTII™ tubes can provide analytically equivalent hs-cTnI results when used on either Alinity™ or Atellica® hs-cTnI assays.

Beyond the fractures: A comprehensive Comparative analysis of Affordable and Accessible laboratory parameters and their coefficients for prediction and Swift confirmation of pulmonary embolism in high-risk orthopedic patients.

Background: Pulmonary embolism (PE) poses a significant challenge in diagnosis and treatment, particularly in high-risk patient populations such as those hospitalized for orthopedic reasons. This study explores the predictive and diagnostic potential of laboratory parameters in identifying PE among orthopedic patients. Objectives: The purpose of this study was to determine whether selected (inexpensive and readily available) laboratory parameters and their coefficients can be used to diagnose pulmonary embolism and whether they are applicable in predicting its occurrence. Material and methods: Selected laboratory parameters were determined twice in 276 hospitalized orthopedic patients with suspected PE: PLT, MPV, NEU, LYM, D-dimer, troponin I, age-adjusted D-dimer and their coefficients. Depending on the angio-CT results, patients were divided into groups. Selected popular laboratory coefficients were calculated and statistically analyzed. Optimal cutoff points were determined for the above laboratory tests and ROC curves were plotted. Results: D-dimer/troponin I [p = 0.008], D-dimer [p = 0.001], age-adjusted D-dimer [p = 0.007], NLR/D-dimer [p = 0.005] and PLR [p = 0.021] are statistically significant predictors of PE. D-dimer/troponin I [p < 0.001], troponin I [p = 0.005] and age-adjusted D-dimer [p = 0.001] correlated with the diagnosis of PE after the onset of clinical symptoms. Conclusions: In the context of orthopedic patients, cost-effective laboratory parameters, particularly the D-dimer/troponin I ratio and age-adjusted D-dimer, exhibit considerable potential in predicting and diagnosing PE. These findings suggest that combining readily available laboratory tests with clinical observation can offer a viable and cost-effective diagnostic alternative, especially in resource-constrained settings. Further studies with larger and diverse patient populations are recommended to validate these results.

Pericardial fluid troponin in cardiac surgery.

BACKGROUND AND OBJECTIVE: Pericardial Fluid (PF) is a rich reservoir of biologically active factors. Due to its proximity to the heart, the biochemical structure of PF may reflect the pathological changes in the cardiac interstitial environment. This manuscript aimed to determine whether the PF level of cardiac troponins changes in patients undergoing cardiac surgery. METHODS: This scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Medline, EMBASE, Cochrane, ClinicalTrials.gov, and Google Scholar databases were electronically searched for primary studies using the keywords "pericardial fluid," "troponin," and "cardiac surgery." The primary outcome of interest was changes in troponin levels within the PF preoperatively and postoperatively. Secondary outcomes of interest included comparisons between troponin level changes in the PF compared to plasma. RESULTS: A total of 2901 manuscripts were screened through a title and abstract stage by two independent blinded reviewers. Of those, 2894 studies were excluded, and the remaining seven studies underwent a full-text review. Studies were excluded if they did not provide data or failed to meet inclusion criteria. Ultimately, six articles were included that discussed cardiac troponin levels within the PF in patients who had undergone cardiac surgery. Pericardial troponin concentration increased over time after surgery, and levels were significantly higher in PF compared to serum. All studies found that the type of operation did not affect these overall observations. CONCLUSION: Our review of the literature suggest that the PF level of cardiac troponins increases in patients undergoing cardiac surgery, irrespective of the procedure type. However, these changes' exact pattern and clinical significance remain undefined.

Interaction of heparin with human cardiac troponin complex and its influence on the immunodetection of troponins in human blood samples.

OBJECTIVES: Heparin is a highly charged polysaccharide used as an anticoagulant to prevent blood coagulation in patients with presumed myocardial infarction and to prepare heparin plasma samples for laboratory tests. There are conflicting data regarding the effects of heparin on the measurement of cardiac isoforms of troponin I (cTnI) and troponin T (cTnT), which are used for the immunodiagnosis of acute myocardial infarction. In this study, we investigated the influence of heparin on the immunodetection of human cardiac troponins. METHODS: Gel filtration (GF) techniques and sandwich fluoroimmunoassay were performed. The regions of сTnI and cTnT that are affected by heparin were investigated with a panel of anti-cTnI and anti-cTnT monoclonal antibodies, specific to different epitopes. RESULTS: Heparin was shown to bind to the human cardiac full-size ternary troponin complex (ITC-complex) and free cTnT, which increased their apparent molecular weights in GF studies. Heparin did not bind to the low molecular weight ITC-complex and to binary cTnI-troponin С complex. We did not detect any sites on cTnI in the ITC-complex that were specifically affected by heparin. In contrast, cTnT regions limited to approximately 69-99, 119-138 and 145-164 amino acid residues (aar) in the ITC-complex and a region that lies approximately between 236 and 255 aar of free cTnT were prone to heparin influence. CONCLUSIONS: Heparin binds to the ITC-complex via cTnT, interacting with several sites on the N-terminal and/or central parts of the cTnT molecule, which might influence the immunodetection of analytes in human blood.

Low Level of First Morning Urine Cardiac Troponin I: A Specific Hallmark of Aortic Stenosis Severity.

Background: It has recently been shown that cardiac-specific troponin I concentrations in first morning urine samples can be measured with commercially available tests. Due to their accumulation in the first morning urine, scientific papers indicate a potential predictive value for cardiovascular diseases. Therefore, the aim of this study was to compare the concentration of cardiac troponin I in the first morning urine in patients with severe aortic stenosis and the healthy population. Patients and Methods: Blood and first morning urine samples were collected from 34 healthy individuals (17 female) at University Hospital Merkur and 25 patients with severe aortic stenosis (14 female) before surgical treatment at University Hospital Dubrava. Cardiac troponin I and T values were determined using high-sensitivity assays using commercially available Abbott and Roche tests. Results: Patients with severe aortic stenosis had significantly lower troponin I concentrations in the first morning urine samples (0.3 ng/L (0.1-0.6)) as compared to the healthy population (15.2 ng/L (8.4-19.9)) (p < 0.001). There was no statistically significant difference in troponin T concentrations between healthy individuals and patients with severe aortic stenosis. In parallel, both I and T plasma troponin concentrations were significantly higher in patients with severe aortic stenosis. Conclusions: In patients with severe aortic stenosis, cardiac troponin I values in the first morning urine are significantly lower than in healthy subjects.

Early Cardiac Evaluation, Abnormal Test Results, and Associations with Outcomes in Patients with Acute Brain Injury Admitted to a Neurocritical Care Unit.

Background: to examine factors associated with cardiac evaluation and associations between cardiac test abnormalities and clinical outcomes in patients with acute brain injury (ABI) due to acute ischemic stroke (AIS), spontaneous subarachnoid hemorrhage (SAH), spontaneous intracerebral hemorrhage (sICH), and traumatic brain injury (TBI) requiring neurocritical care. Methods: In a cohort of patients ≥18 years, we examined the utilization of electrocardiography (ECG), beta-natriuretic peptide (BNP), cardiac troponin (cTnI), and transthoracic echocardiography (TTE). We investigated the association between cTnI, BNP, sex-adjusted prolonged QTc interval, low ejection fraction (EF < 40%), all-cause mortality, death by neurologic criteria (DNC), transition to comfort measures only (CMO), and hospital discharge to home using univariable and multivariable analysis (adjusted for age, sex, race/ethnicity, insurance carrier, pre-admission cardiac disorder, ABI type, admission Glasgow Coma Scale Score, mechanical ventilation, and intracranial pressure [ICP] monitoring). Results: The final sample comprised 11,822 patients: AIS (46.7%), sICH (18.5%), SAH (14.8%), and TBI (20.0%). A total of 63% (n = 7472) received cardiac workup, which increased over nine years (p < 0.001). A cardiac investigation was associated with increased age, male sex (aOR 1.16 [1.07, 1.27]), non-white ethnicity (aOR), non-commercial insurance (aOR 1.21 [1.09, 1.33]), pre-admission cardiac disorder (aOR 1.21 [1.09, 1.34]), mechanical ventilation (aOR1.78 [1.57, 2.02]) and ICP monitoring (aOR1.68 [1.49, 1.89]). Compared to AIS, sICH (aOR 0.25 [0.22, 0.29]), SAH (aOR 0.36 [0.30, 0.43]), and TBI (aOR 0.19 [0.17, 0.24]) patients were less likely to receive cardiac investigation. Patients with troponin 25th-50th quartile (aOR 1.65 [1.10-2.47]), troponin 50th-75th quartile (aOR 1.79 [1.22-2.63]), troponin >75th quartile (aOR 2.18 [1.49-3.17]), BNP 50th-75th quartile (aOR 2.86 [1.28-6.40]), BNP >75th quartile (aOR 4.54 [2.09-9.85]), prolonged QTc (aOR 3.41 [2.28; 5.30]), and EF < 40% (aOR 2.47 [1.07; 5.14]) were more likely to be DNC. Patients with troponin 50th-75th quartile (aOR 1.77 [1.14-2.73]), troponin >75th quartile (aOR 1.81 [1.18-2.78]), and prolonged QTc (aOR 1.71 [1.39; 2.12]) were more likely to be associated with a transition to CMO. Patients with prolonged QTc (aOR 0.66 [0.58; 0.76]) were less likely to be discharged home. Conclusions: This large, single-center study demonstrates low rates of cardiac evaluations in TBI, SAH, and sICH compared to AIS. However, there are strong associations between electrocardiography, biomarkers of cardiac injury and heart failure, and echocardiography findings on clinical outcomes in patients with ABI. Findings need validation in a multicenter cohort.

Elevated Troponins after COVID-19 Hospitalization and Long-Term COVID-19 Symptoms: Incidence, Prognosis, and Clinical Outcomes-Results from a Multi-Center International Prospective Registry (HOPE-2).

Background: Acute cardiac injury (ACI) after COVID-19 has been linked with unfavorable clinical outcomes, but data on the clinical impact of elevated cardiac troponin on discharge during follow-up are scarce. Our objective is to elucidate the clinical outcome of patients with elevated troponin on discharge after surviving a COVID-19 hospitalization. Methods: We conducted an analysis in the prospective registry HOPE-2 (NCT04778020). Only patients discharged alive were selected for analysis, and all-cause death on follow-up was considered as the primary endpoint. As a secondary endpoint, we established any long-term COVID-19 symptoms. HOPE-2 stopped enrolling patients on 31 December 2021, with 9299 patients hospitalized with COVID-19, of which 1805 were deceased during the acute phase. Finally, 2382 patients alive on discharge underwent propensity score matching by relevant baseline variables in a 1:3 fashion, from 56 centers in 8 countries. Results: Patients with elevated troponin experienced significantly higher all-cause death during follow-up (log-rank = 27.23, p < 0.001), and had a higher chance of experiencing long-term COVID-19 cardiovascular symptoms. Specifically, fatigue and dyspnea (57.7% and 62.8%, with p-values of 0.009 and <0.001, respectively) are among the most common. Conclusions: After surviving the acute phase, patients with elevated troponin on discharge present increased mortality and long-term COVID-19 symptoms over time, which is clinically relevant in follow-up visits.

DANSPOT: A Multicenter Stepped-Wedge Cluster-Randomized Trial of the Reclassification of Acute Myocardial Infarction: Rationale and Study Design.

BACKGROUND: Cardiac troponins are the preferred biomarkers for the diagnosis of acute myocardial infarction. Although sex-specific 99th percentile thresholds of troponins are recommended in international guidelines, the clinical effect of their use is poorly investigated. The DANSPOT Study (The Danish Study of Sex- and Population-Specific 99th percentile upper reference limits of Troponin) aims to evaluate the clinical effect of a prospective implementation of population- and sex-specific diagnostic thresholds of troponins into clinical practice. METHODS: This study is a nationwide, multicenter, stepped-wedge cluster-randomized trial of the implementation of population- and sex-specific thresholds of troponins in 22 of 23 clinical centers in Denmark. We established sex-specific thresholds for 5 different troponin assays based on troponin levels in a healthy Danish reference population. Centers will sequentially cross over from current uniform manufacturer-derived thresholds to the new population- and sex-specific thresholds. The primary cohort is defined as patients with symptoms suggestive of acute coronary syndrome having at least 1 troponin measurement performed within 24 hours of arrival with a peak troponin value between the current uniform threshold and the new sex-specific female and male thresholds. The study will compare the occurrence of the primary outcome, defined as a composite of nonfatal myocardial infarction, unplanned revascularization, and all-cause mortality within 1 year, separately for men and women before and after the implementation of the new sex-specific thresholds. CONCLUSIONS: The DANSPOT Study is expected to show the clinical effects on diagnostics, treatment, and clinical outcomes in patients with myocardial infarction of implementing sex-specific diagnostic thresholds for troponin based on a national Danish reference population. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05336435.