hsTnT Levels Research Articles

Higher Troponin Levels on Admission are associated With Persistent Cardiac Magnetic Resonance Lesions in Children Developing Myocarditis After mRNA-Based COVID-19 Vaccination.

Acute pericarditis/myocarditis is a rare complication of the mRNA-based vaccines and although mostly self-limiting, long-term sequelae remain unclear. We enrolled all patients admitted to the emergency department between September 2021 and February 2022 meeting the CDC work case definition, with symptoms onset after mRNA-based COVID-19 vaccine. Alternative virologic causes were excluded. Clinical data, laboratory values, cardiologic evaluation, electrocardiogram (ECG), and echocardiogram (ECHO) were collected on admission, at discharge, and during follow-up in all patients. Cardiac Magnetic Resonance (CMR) was performed only in those with signs consistent with myocarditis. We observed 13 patients (11M and 2F), median age 15 years, affected by acute pericarditis/myocarditis after COVID-19 mRNA vaccination (11 after Comirnaty® and 2 after Spikevax®). Symptoms'onset occurred at a median of 5 days (range, 1 to 41 days) after receiving mRNA vaccine (13 Prizer 2 Moderna): 4 patients (31%) after the 1st dose, 6 (46%) after the 2nd, and 3 (23%) after 3rd dose. Increased levels of high-sensitive troponin T (hsTnT) (median 519,5 ng/mL) and N-terminal-pro hormone BNP (NT-proBNP) (median 268 pg/mL) and pathognomonic ECG and ECHO abnormalities were detected. On admission, 7 of 13 (54%) presented with myopericarditis, 3 (23%) with myocarditis, and 3 (23%) with pericarditis; CMR was performed in 5 patients upon pediatric cardiologist prescription and findings were consistent with myocarditis. At 12 weeks of follow-up, all but one patient (92%), still presenting mild pericardial effusion at ECHO, were asymptomatic with normal hsTnT and NT-proBNP levels and ECG. On CMR 6 of 9 patients showed persistent, although decreased, myocardial injury. Higher hsTnT levels on admission significantly correlated with persistent CMR lesions. Evidence of persistent CMR lesions highlights the need for a close and standardized follow-up for those patients who present high hsTnT levels on admission.

Use of serial changes in biomarkers vs. baseline levels to predict left ventricular remodelling after STEMI.

Cellular communication network factor 1 (CCN1) is an independent predictor of MACE after ACS and elevated levels correlated with infarct size after STEMI. We compared the prognostic accuracy of baseline levels of CCN1, NT-proBNP, hsTnT, and ST2 and changes in levels over time to predict the development of structural and functional alterations typical of LV remodelling. Serial 3-T cMRI scans were performed to determine LVEF, LVEDV, LVESV, infarct size, and relative infarct size, which were correlated with serial measurements of the four biomarkers. The prognostic significance of these biomarkers was assessed by multiple logistic regression analysis by examining their performance in predicting dichotomized cardiac MRI values 12months after STEMI based on their median. For each biomarker three models were created using baseline (BL), the Δ value (BL to 6months), and the two values together as predictors. All models were adjusted for age and renal function. Receiver operator curves were plotted with area under the curve (AUC) to discriminate the prognostic accuracy of individual biomarkers for MRI-based structural or functional changes. A total of 44 predominantly male patients (88.6%) from the ETiCS (Etiology, Titre-Course, and Survival) study were identified at a mean age of 55.5±11.5 (SD) years treated by successful percutaneous coronary intervention (97.7%) at a rate of 95.5% stent implantation within a median pain-to-balloon time of 260min (IQR 124-591). Biomarkers hsTnT and ST2 were identified as strong predictors (AUC>0.7) of LVEDV and LVEF. BL measurement to predict LVEF [hsTnT: AUC 0.870 (95% CI: 0.756-0.983), ST2: AUC 0.763 (95% CI: 0.615-0.911)] and the Δ value BL-6M [hsTnT: AUC 0.870 (95% CI: 0.756-0.983), ST2: AUC 0.809 (95% CI: 0.679-0.939)] showed a high prognostic value without a significant difference for the comparison of the BL model vs. the Δ-value model (BL-6M) for hsTnT (P=1) and ST2 (P=0.304). The combined model that included baseline and Δ value as predictors was not able to improve the ability to predict LVEF [hsTnT: AUC 0.891 (0.791-0.992), P=0.444; ST2: AUC 0.778 (0.638-0.918), P=0.799]. Baseline levels of CCN1 were closely associated with LVEDV at 12months [AUC 0.708 (95% CI: 0.551-0.865)] and infarct size [AUC 0.703 (95% CI: 0.534-0.872)]. Baseline biomarker levels of hsTnT and ST2 were the strongest predictors of LVEF and LVEDV at 12months after STEMI. The association of CCN1 with LVEDV and infarct size warrants further study into the underlying pathophysiology of this novel biomarker.

Association of Serial High-Sensitivity Cardiac Troponin T With Subsequent Cardiovascular Events in Patients Stabilized After Acute Coronary Syndrome

Studies have demonstrated an association between single measures of high-sensitivity troponin (hsTn) and future cardiovascular events in patients with chronic coronary syndromes. However, limited data exist regarding the association between changes in serial values of hsTn and subsequent cardiovascular events in this patient population. To evaluate the association between changes in high-sensitivity troponin T (hsTnT) and subsequent cardiovascular events in patients stabilized after acute coronary syndrome (ACS). This is a secondary analysis from the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT), a randomized clinical trial of ezetimibe vs placebo on a background of simvastatin in 18 144 patients hospitalized for an ACS across 1147 sites in 39 countries. The current biomarker substudy includes the 6035 participants consenting to the biomarker substudy with available hsTnT at months 1 and 4. Data were collected from October 26, 2005, through July 8, 2010, with the database locked October 21, 2014. Data were analyzed from February 28, 2021, through August 14, 2022. The outcomes of interest were cardiovascular death, myocardial infarction (MI), stroke, or hospitalization for heart failure (HHF). Associations of absolute and relative changes in hsTnT between month 1 and month 4 as a function of the starting month 1 hsTnT and the composite outcome were examined using landmark analyses. Of 6035 patients in this analysis (median [IQR] age, 64 [57-71]), 1486 (24.6%) were female; 361 (6.0%) were Asian; 121 were (2.0%) Black; 252 (4.2%) were Spanish descent; 4959 were (82.2%) White; and 342 (5.7%) reported another race (consolidated owing to small numbers), declined to respond, or were not asked to report race owing to regulatory prohibitions. Most patients (4114 [68.2%]) had stable hsTnT values (change <3 ng/L), with 1158 (19.2%) and 763 (12.6%) having changes of 3 to less than 7 ng/L and 7 ng/L or more, respectively. After adjustment for clinical risk factors and stratification by the starting month 1 hsTnT level, an absolute increase in hsTnT of 7 ng/L or more was associated with a more than 3-fold greater risk of the composite outcome (adjusted hazard ratio [aHR], 3.33; 95% CI, 1.99-5.57; P < .001), whereas decreases of 7 ng/L or more were associated with similar to lower risk (aHR, 0.51; 95% CI, 0.26-1.03; P = .06) compared with stable values. There was a stepwise association moving from larger absolute decreases (aHR, 0.51; 95% CI, 0.26-1.03) to larger absolute increases (aHR, 3.33; 95% CI, 1.99-5.57) in hsTnT with future risk of the composite outcome (P trend <.001). A similar association was observed when analyzed on the basis of relative percent and continuous change. Among stable patients post-ACS, changes in hsTnT were associated with a gradient of risk of subsequent cardiovascular events across the range of starting hsTnT values. Serial assessment of hsTnT may refine risk stratification with the potential to guide therapy decisions in this patient population. ClinicalTrials.gov Identifier: NCT00202878.

Markers of Infection-Mediated Cardiac Damage in Influenza and COVID-19.

Introduction: Influenza and the coronavirus disease 2019 (COVID-19) are two potentially severe viral infections causing significant morbidity and mortality. The causative viruses, influenza A/B and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) can cause both pulmonary and extra-pulmonary disease, including cardiovascular involvement. The objective of this study was to determine the levels of cardiac biomarkers in hospitalized patients infected with influenza or COVID-19 and their correlation with secondary outcomes. Methods: We performed a retrospective comparative analysis of cardiac biomarkers in patients hospitalized at our department with influenza or COVID-19 by measuring high-sensitivity troponin-T (hs-TnT) and creatinine kinase (CK) in plasma. Secondary outcomes were intensive care unit (ICU) admission and all-cause in-hospital mortality. Results: We analyzed the data of 250 influenza patients and 366 COVID-19 patients. 58.6% of patients with influenza and 46.2% of patients with COVID-19 presented with increased hs-TnT levels. Patients of both groups with increased hs-TnT levels were significantly more likely to require ICU treatment or to die during their hospital stay. Compared with COVID-19, cardiac biomarkers were significantly higher in patients affected by influenza of all age groups, regardless of pre-existing cardiovascular disease. In patients aged under 65 years, no significant difference in ICU admission and mortality was detected between influenza and COVID-19, whereas significantly more COVID-19 patients 65 years or older died or required intensive care treatment. Conclusions: Our study shows that increased cardiac biomarkers are associated with higher mortality and ICU admission in both, influenza and SARS-CoV-2-infected patients. Cardiac biomarkers are higher in the influenza cohort; however, this does not translate into worse outcomes when compared with the COVID-19 cohort.

NT-proBNP is superior to novel plasma biomarkers for predicting adverse outcome in arrhythmogenic right ventricular cardiomyopathy

Abstract Background/Introduction Arrhythmogenic right ventricular cardiomyopathy is a heritable heart muscle disease characterized by progressive substitution of the myocardium with fibrous and fatty tissue, which is the substrate for ventricular arrhythmia, systolic dysfunction and heart failure. Determining the optimal time for heart transplantation is challenging and, therefore, finding risk factors for disease progression is needed. Purpose The purpose of the study was to evaluate the role of markers of myocardial fibrosis sST2, Gal-3, MMP-2 and MMP-9, as well as NT-proBNP and hsTnT, in predicting major adverse outcomes in ARVC. Moreover, we aimed to identify other risk factors for developing end-stage heart failure. Methods We included 91 patients with the definite diagnosis of ARVC according to the 2010 Task Force Criteria (59 males, mean age of 47±16 years). Patients were interviewed for their medical history, electrocardiography and echocardiography were performed and plasma levels of selected biomarkers were measured. Thereafter, subjects were followed for the occurrence of the composite endpoint of death or heart transplantation (HTx) and major arrhythmic events defined as ventricular fibrillation, sustained ventricular tachycardia or appropriate implantable cardioverter-defibrillator intervention. Results During the median follow-up of 36,4 months [29,8–41,2], 13 subjects (14%) reached the composite endpoint of death or HTx and 27 subjects (30%) experienced major arrhythmic event. Among the studied biomarkers, significantly higher levels of sST2, MMP-2, NT-proBNP and hsTnT were found in patients who achieved the composite endpoint. The remaining prognostic factors are shown in Table 1. In the multivariate analysis, three factors turned out to be significant: higher NT-proBNP levels (the cut-off point ≥890.3 pg/m), greater right ventricular end-diastolic area (the cut-off point ≥39.0 cm2) and history of atrial tachycardia. Kaplan-Meyer survival analysis depending on the number of predictors is presented in Figure 1. None of the biomarkers predicted major arrhythmic events. Conclusions NT-proBNP ≥890.3 pg/ml, RV area ≥39.0 cm2 and history of atrial tachycardia are independent risk factors for death or HTx in ARVC. Among the studied biomarkers, higher levels of sST2, MMP-2, NT-proBNP and hsTnT were observed in patients who reached the composite endpoint. Biomarkers had no value in predicting ventricular arrhythmias. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): National Institute of Cardiology, Warsaw, Poland

Prognostic importance of NT-proBNP following high-risk myocardial infarction in the PARADISE-MI Trial

Abstract Background/Introduction N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a marker of ventricular wall stress and a potent predictor of death and heart failure (HF) across multiple populations (from healthy insurance applicants to various disease entities). Purpose To evaluate the prognostic importance of NT-proBNP in patients with acute myocardial infarction (AMI) complicated by left ventricular systolic dysfunction, pulmonary congestion, or both and ≥1 of 8 predefined risk-augmenting factors (age ≥70 years, diabetes, previous MI, eGFR &amp;lt;60 ml/min/1.73 m2, atrial fibrillation, LVEF &amp;lt;30%, Killip class III/IV, or ST elevation MI without reperfusion) enrolled in PARADISE-MI. Methods Patients were randomized to sacubitril/valsartan 200mg or ramipril 5mg twice daily within 0.5 to 7 days of presenting with an AMI. Patients with prior HF were excluded. NT-proBNP and high-sensitivity troponin T (hsTnT) were collected at randomization in a prespecified sub-study of 1129 patients. The primary endpoint of PARADISE-MI was a time-to-first composite of cardiovascular (CV) death or incident HF (hospitalization or outpatient symptomatic HF); secondary endpoints included all-cause death and the composite of fatal or non-fatal MI or stroke. Results Median NT-proBNP was 1757 pg/ml [interquartile range, 896–3462 pg/ml] at randomization (4.0±1.8 days after presentation with the index MI). Patients with higher NT-proBNP levels at baseline were older, more commonly women and more frequently had hypertension, atrial fibrillation, renal dysfunction, and pulmonary congestion at randomization (all p&amp;lt;0.001). NT-proBNP concentrations were only weakly correlated with levels of hsTnT at randomization (r=0.38, p&amp;lt;0.001). NT-proBNP at baseline was strongly associated with the primary composite endpoint (adjusted HR 1.45 per doubling NT-proBNP; 95% CI, 1.23–1.70), independent of clinical variables as well as hsTnT (Figure). NT-proBNP was also independently associated with all-cause death (aHR 1.74; 95% CI, 1.38–2.21) and fatal or non-fatal MI or stroke (aHR 1.24; 95% CI, 1.05–1.45). The relative effect of sacubitril/valsartan versus ramipril on the primary composite endpoint was not statistically different across the spectrum of NT-proBNP (p-interaction = 0.46). Conclusions When assessed within the first week of a high risk AMI NT-proBNP is not only associated with incident HF and death but also with atherosclerotic events and provides prognostic information that is independent of hsTnT in this post AMI population. Funding Acknowledgement Type of funding sources: None.

Quality matters: low-density lipoprotein electronegativity but not quantity determines mortality risk in acute coronary syndromes

Abstract Background Changes in the protein composition of low-density lipoprotein (LDL) particles induce a shift in their electronegativity, a phenomenon implicated in both pro-inflammatory and pro-atherogenic signalling (1). While high levels of LDL foster the build-up of atherosclerotic plaques, and as such the susceptibility for the development of acute coronary syndromes (ACS), LDL levels assessed at the time of presentation fail to associate with fatal events following the index event (2). Experimental data suggest that altered LDL electronegativity exerts functional effects on both the myocardium and vasculature (1,3). Purpose We aimed to study the association between LDL electronegativity, assessed at the time of acute presentation, and all-cause mortality following the index ACS. Methods We designed a case-cohort study in 2'619 ACS patients prospectively recruited in the investigator-driven, multicentre SPUM-ACS study (ClinicalTrials.gov Identifier: NCT01000701). Plasma LDL levels were quantified at baseline and LDL was chromatographically resolved into 5 subfractions (L1-L5), with the L1/L5 ratio serving as a proxy for overall LDL electronegativity. By employing least-squares ordinary regression models determinants of plasma L1, L5, and the L1/5 ratio were studied, and the association with mortality of both LDL levels and its electronegativity were estimated using weighted Cox regression models. Results Cases and controls showed similar lipid profiles, but distinct LDL electronegativity, demonstrated by an increase in the L1/L5 ratio in cases vs. controls (P&amp;lt;0.05; Fig. 1). The highest-ranked determinants of the L1/L5 ratio were total cholesterol, LDL, high-density lipoprotein, age and triglycerides. Higher L1/L5 ratios were associated with increased risk all-cause and cardiovascular death at both 30-day (adjusted [adj.] hazard ratio [HR], 2.35, 95% confidence interval [CI], 1.81–3.03, and 2.37, 95% CI, 1.83–3.07, per standard-deviation [SD] increase) and 1-year intervals (adj. HR, 1.88, 95% CI 1.43–2.46, and 1.81, 95% CI 1.36–2.42 per SD increase). In contrast, LDL levels were not associated with these outcomes, neither at 30-day (adj. HR, 1.20, 95% CI, 0.64–2.24, and 1.20, 95% CI, 0.64–2.56 per SD increase) nor 1-year intervals (adj. HR, 1.35, 95% CI, 0.69–2.63, and 1.25, 95% CI 0.56–2.78 per SD increase). These associations were independent of age, sex, cardiometabolic risk factors and baseline risk, as assessed by the updated GRACE score. When compared with established risk factors (hsTnT levels, BMI, Killip class, eGFR, LDL levels), the L1/L5 ratio superseded several risk factors as an independent predictor for fatal events following ACS (Fig. 2). Conclusions In contemporary patients with ACS, LDL electronegativity independently predicts fatal events after the acute event, while LDL levels do not. Our results suggest that LDL quality rather than quantity provides predictive utility for premature death within 1 year after the index ACS. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swiss National Science FoundationSwiss Heart FoundationTheodor-Ida Herzog StiftungFoundation for Cardiovascular Research – Zurich Heart House

Predictors of Stress-Delta High-Sensitivity Troponin T in Emergency Department Patients Undergoing Stress Testing.

Background and objective Elevations in high-sensitivity troponin T (hs-TnT) are frequently observed following extreme physical exercise. In light of this, we sought to determine whether specific clinical characteristics are associated with this phenomenon in patients undergoing cardiac exercise tolerance testing (ETT). Methods We conducted a retrospective analysis of a prospectively collected biospecimen repository of 257 patients undergoing a stress echocardiogram forpossible acute coronary syndrome (ACS). Ischemic electrocardiogram (ECG) changes during ETT and the presence or absence of ischemia on imaging were determined by a board-licensed cardiologist. N-terminalpro-brain natriuretic peptide (NT-proBNP) and hs-TnT assays were obtained immediately before and two hours following ETT. We developed linear regression models including several clinical characteristics to predict two-hour stress-delta hs-TnT. Variable selection was performed using theleast absolute shrinkage and selection operator (LASSO). Results The mean age of the patients was 52 years [standard deviation (SD): 11.4]; 125 (48.6%) of them were men, and 88 (34.2%) were African-American. Twenty-two patients (8.6%) had ischemia evident on echocardiography, and 31 (12.1%) had ischemic ECG changes during exercise. The mean baseline hs-TnT was 5.6 ng/L (SD: 6.4) and the mean two-hour hs-TnT was 7.1 ng/L (SD: 10.2). Age and ischemic ECG changes were associated with two-hour stress-delta hs-TnT values. Conclusions Based on our findings, ischemic changes in stress ECG and age were associated with an increase in hs-TnT levels following exercise during a stress echo.

Insulin-like growth factor binding protein 7 (IGFBP7), a link between heart failure and senescence.

Insulin like growth factor binding protein 7 (IGFBP7) is a marker of senescence secretome and a novel biomarker in patients with heart failure (HF). We evaluated the prognostic value of IGFBP7 in patients with heart failure and examined associations to uncover potential new pathophysiological pathways related to increased plasma IGFBP7 concentrations. We have measured plasma IGFBP7 concentrations in 2250 subjects with new-onset or worsening heart failure (BIOSTAT-CHF cohort). Higher IGFBP7 plasma concentrations were found in older subjects, those with worse kidney function, history of atrial fibrillation, and diabetes mellitus type 2, and in subjects with higher number of HF hospitalizations. Higher IGFBP7 levels also correlate with the levels of several circulating biomarkers, including higher NT-proBNP, hsTnT, and urea levels. Cox regression analyses showed that higher plasma IGFBP7 concentrations were strongly associated with increased risk of all three main endpoints (hospitalization, all-cause mortality, and combined hospitalization and mortality) (HR 1.75, 95% CI 1.25-2.46; HR 1.71, 95% CI 1.39-2.11; and HR 1.44, 95% CI 1.23-1.70, respectively). IGFBP7 remained a significant predictor of these endpoints in patients with both reduced and preserved ejection fraction. Likelihood ratio test showed significant improvement of all three risk prediction models, after adding IGFBP7 (P<0.001). A biomarker network analysis showed that IGFBP7 levels activate different pathways involved in the regulation of the immune system. Results were externally validated in BIOSTAT-CHF validation cohort. IGFPB7 presents as an independent and robust prognostic biomarker in patients with HF, with both reduced and preserved ejection fraction. We validate the previously published data showing IGFBP7 has correlations with a number of echocardiographic markers. Lastly, IGFBP7 pathways are involved in different stages of immune system regulation, linking heart failure to senescence pathways.

To Study the 99th Percentile Upper Reference Limit of High Sensitive Troponin T in adult population of Multan

Aim: To determine 99th percentile upper reference limit of high sensitive Troponin T in adult population of Multan Methodology: A cross sectional study conducted in the department of chemical pathology, CMH, Multan from September 2021 to March 2022. Approval by the institutional review board was taken. Sample size was 265 cases. Results: Mean age was 46.2 + 12.7 years. 131(49.6%) were females and 134 (50%) were males. In 265 cases, there were 210 (79.24%) cases who had hs-TnT level of &gt;2.99 ng/L and 55 (20.75%) have values of hs-TnT &lt;3.0 ng/L. Cases having a level of &lt;3.0 were assigned a value of 2.9 ng/L for statistical analysis. Kruskal-Wallis test was used to analyze significance in troponin level regarding age and gender. hs-cTnT values were found statistically significant between genders while non significant difference between age groups. Conclusion: hs-cTnT value was 18.20 ng/L in the study cases while these values were 30.46ng/L for males and 16.77ng/L for females. It is concluded that overall 99th percentile values of hs-cTnT are significantly higher among men as compared to women. Key words: High sensitive Troponin T, Adults, percentile

High-sensitivity troponin T in preterm infants with a hemodynamically significant patent ductus arteriosus

Background: The incidence of patent ductus arteriosus (PDA) is inversely related to gestational age. Cardiac troponin T (cTnT) is a specific marker for myocardial ischemic injury. The aim of this work was to investigate if a hemodynamically significant patent ductus arteriosus leads to elevated high- sensitivity troponin T (hsTnT) levels in serum. Methods: This prospective observational research included 60 preterm infants &lt;34 weeks’ gestation, weighing &lt;1500 g with PDA. Patients were classified into two groups according to the ECHO findings: Group A: preterm infants who had hs.PDA (PDA &gt;1.5 mm and LA: Ao &gt;1.2 and group B: preterm infants without hs.PDA. All cases were subjected to clinical examination, echocardiogram and hsTnT assay. Results: Serum hsTnT levels was significantly elevated in patients with hs PDA compared to patients without hs PDA. High sensitive T-troponin can significantly detect hsPDA with AUC of 0.986, P value &lt;0.001. At cut off &gt;100 pg/ml, it’s a significant detector with sensitivity of 93.33%, specificity of 90%, PPV of 90.3, NPV of 93.1 and diagnostic accuracy of 91.5%. PDA had a significant positive correlation with hsTnT (r=0.803, P&lt;0.001). Conclusions: HsTnT can significantly detect hemodynamically significant PDA in preterm infants with high sensitivity and specificity.

Association of Chest Pain Protocol–Discordant Discharge With Outcomes Among Emergency Department Patients With Modest Elevations of High-Sensitivity Troponin

Accelerated diagnostic protocols (ADPs) for chest pain using high-sensitivity troponin (hsTn) levels have excellent sensitivity and negative predictive value for rapid risk stratification of patients with chest pain. However, little is known about the outcomes of patients who are discharged despite abnormal ADP results, ie, after "ruling-in" with a modest elevation of hsTn. To determine outcomes of patients discharged following ADP, including those who were ruled in with modestly elevated levels of hsTnT but discharged nonetheless. This retrospective cohort study included patients with chest pain who presented to the emergency departments (EDs) of a large multisite health system ED between January 2017 to September 2019. Patients were assessed using an ADP, had a peak hsTnT level measured between the limit of quantitation and 52 ng/L, were discharged, and had follow-up in the electronic medical record. Data analysis was conducted from January 2017 to September 2019. Application of an hsTnT ADP. Thirty-day major adverse cardiac events (MACE), including myocardial infarction, urgent coronary revascularization, and all-cause death, comparing patients who were discharged following ADP-concordant vs ADP-discordant results. Of 10 342 patients with chest pain (mean [SD] age 51 [17] years; 5902 [57%] women) discharged following ADP, 29 (0.28%) had MACE. Patients with MACE were older (median [IQR] age, 66 [53-75] years vs 50 [38-62] years; P < .001) and more likely to have prior CAD (12 [41.4%] vs 1805 [17.5%]; P = .002) and hyperlipidemia (13 [44.8%] vs 2248 [21.8%]; P = .006). Additionally, patients with MACE were 5-fold more likely to have been discharged despite ADP discordance (16 [55.2%] vs 1145 [11.1%]; P < .001). A multivariable logistic regression analysis revealed only ADP discordance was independently associated with MACE (odds ratio, 6.42 [95% CI, 2.94-14.0]; P < .001). When stratified by peak hsTnT level, there were no differences in MACE between ADP-concordant and -discordant discharges provided the peak hsTnT measured was less than 12 ng/L. In contrast, patients with peak hsTnT level between 12 and 51 ng/L were significantly more likely to have MACE if they were discharged after ADP-discordant vs -concordant hsTnT series (14 of 609 [2.30%] vs 5 of 1047 [0.48%]; P < .002). Notably, a HEART (history, electrocardiogram, age, risk factors, troponin) score of 4 or greater retrospectively identified the most ADP-discordant discharges (13 of 16 [81.3%]) who had MACE. In this cohort study, an hsTnT ADP identified patients who could be discharged from the ED with low 30-day risk of MACE, provided the discharge was based on ADP-concordant "rule-out." Conversely, the rate of MACE was significantly higher among patients discharged despite ADP discordance. Most patients with ADP-discordant discharges who experienced MACE had a HEART score of 4 or greater, suggesting that application of this score may augment discharge decisions of patients despite ADP-discordant troponin series.

Myocardial injury in stress echocardiography: Comparison of dobutamine, dipyridamole and dynamic stressors-single center study.

In stress echocardiography (SE), dipyridamole (DIP) and dynamic stress (ExSE) are reported as being safer than dobutamine stress echocardiography (DSE). We investigated whether these commonly used stressors cause myocardial injury, measured by high sensitivity troponin T (hsTnT). One hundred and thirty five patients (DSE n = 46, ExsE n = 46, DIP n = 43) with negative result of SE were studied. The exclusion criteria were known ischaemic heart disease (IHD), baseline wall motion abnormalities, left ventricle systolic dysfunction/regional wall motion abnormalities, septum/posterior wall ≥13 mm, diabetes/pre-diabetes, baseline hsTnT level ≥14 ng/L, baseline blood pressure ≥160/100 mmHg, peak pulmonary pressure ≥45mmHg, eGFR <1ml/s/1.73m2 , more than mild to moderate valvular disease and dobutamine side effects. HsTnT was measured before and 180 minutes after the test. All patients had low pre-test probabilities of having obstructive IHD. HsTnT increased in DSE, less so in ExSE, and was unchanged in the DIP group (∆hsTnT 9.4 [1.5-58.6], 1.1 [-0.9-15.7], -0.1 [-1.4-2.1] ng/L, respectively, p<0.001). In DSE, the ∆hsTnT was associated with peak dobutamine dose (r = 0.30, p = 0.045), test length (r = 0.43, p = 0.003) and atropine use (p<0.001). In ExSE, the hsTnT increase was more likely in females (p = 0.012) and the elderly (>65 years) (r = 0.32, p = 0.03); no association was found between atropine use (p = 0.786) or test length and ∆hsTnT (r = 0.10, p = 0.530). DSE is associated with myocardial injury in patients with negative SE, no injury was observed in DIP and only mild case in ExSE. Whether myocardial injury is causative of the higher reported adverse event rates in DSE remains to be determined.

Role of High-Sensitivity Troponin-T And N-Terminal Pro B-Type Natriuretic Peptide as an Early Predictor of Myocardial Dysfunction in Aneurysmal Subarachnoid Hemorrhage: A Prospective Observational Study.

Acute cardiac complications are commonly seen in aneurysmal subarachnoid hemorrhage (aSAH) patients and may vary from subclinical electrocardiographic abnormalities, or reduced ejection fraction on echocardiography, elevated levels of cardiac markers (cardiac troponin and Brain natriuretic peptide) to heart failure. This study was done to evaluate the role of cardiac markers (high-sensitive Troponin-T and N-terminal pro-B-type natriuretic peptide) in early identification of cardiac complications and hence dysfunction. All consecutive patients with aSAH without any previous cardiac history were included. At admission, neurological evaluation using Hunt and Hess grading (H and H grade), with electrocardiography to look for any changes, echocardiography for ejection fraction, and any wall motion abnormalities was also done. The serial serum levels of high-sensitive Troponin-T (hsTnT) and N-terminal pro B-type natriuretic peptide (NT pro-BNP) for 7 consecutive days was measured with hsTnT >0.14 ng/ml and NT pro-BNP >150 pg/mL considered elevated. A total of 69 patients were included. The elevated peak level of hsTnT and NT pro-BNP was seen in 55.1% and 69.6% of patients. A positive correlation was seen between hsTnT (P = 0.033) and NT pro-BNP (P = 0.011) and poor SAH grade (H and H grade 3-5), similarly, abnormal ECG also significantly correlated with elevated peak hsTnT (P = 0.002) and NT proBNP (P = 0.000). Also, significant difference in peak hsTnT (P = 0.000) and NT-proBNP (P = 0.000) in patients with or without reduced ejection fraction (EF). The elevated peak levels of hsTnT and NTproBNP along with ECG and echocardiography abnormalities may help in early identification of myocardial injury, hence cardiac dysfunction.

Growth Differentiation Factor-15, High-Sensitivity Cardiac Troponin T, and N-Terminal pro-B-type Natriuretic Peptide for Predicting Risk of Venous Thromboembolism in Ambulatory Cancer Patients Receiving Chemotherapy.

Growth differentiation factor-15 (GDF-15), high-sensitivity cardiac troponin T (hs-TnT), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are associated with increased risk of venous thromboembolism (VTE) in noncancer patients. However, the performance of these biomarkers in cancer patients is unknown. Our objective was to assess performance of these biomarkers in predicting VTE in cancer patients at intermediate to high risk for VTE (Khorana Score ≥ 2). We used 1-month plasma samples from AVERT trial patients to determine if GDF-15, NT-proBNP, and hs-TnT levels are associated with VTE incidence between 1 and 7 months from the start of chemotherapy. The minimal Euclidean distance of the receiver operating characteristic curve was used to derive optimal cut-offs for GDF-15 and NT-proBNP given there was no evidence of a commonly used cut-off. Logistic and Fine and Gray competing risk regression analyses were used to calculate odds ratios (ORs) and subdistribution hazard ratios, respectively, while adjusting for age, sex, anticoagulation, and antiplatelet therapy. We tested in two groups: all patients (n = 476, Model 1) and all patients with nonprimary brain cancers (n = 454, Model 2). In models 1 and 2, GDF-15 ≥2,290.9 pg/mL had adjusted ORs for VTE of 1.65 (95% confidence interval [CI]: 0.89-3.08), and 2.28 (95% CI: 1.28-4.09), respectively. hs-TnT ≥14.0 pg/mL was associated with higher odds of VTE in models 1 and 2 (adjusted ORs: 2.26 [95% CI: 1.40-3.65] and 2.03 [95% CI: 1.07-3.84], respectively). For NT-proBNP, levels ≥183.5 pg/mL were not associated with VTE. Similar results were observed in the Fine and Gray analysis. Our results indicate that increased GDF-15 and hs-TnT levels predicted increased VTE risk.

Cardiac Biomarkers and Risk of Atherosclerotic Cardiovascular Disease in Patients with CKD.

Several cardiac biomarkers of cardiac stress, inflammation, and fibrosis (N-terminal pro brain-type natriuretic peptide [NT-proBNP], high-sensitivity troponin T [hsTnT], growth differentiation factor 15 [GDF-15], and soluble ST2 [sST2]) have been associated with atherosclerotic disease in the general population. We hypothesized that these cardiac biomarkers may also be associated with the atherosclerotic cardiovascular disease in patients with CKD. We analyzed levels of NT-proBNP, hsTnT, GDF-15, and sST2 in a cohort of 2732 participants with mild to moderate CKD from the Chronic Renal Insufficiency Cohort (CRIC) study. Outcomes included incident atherosclerotic disease, defined as the first instance of myocardial infarction, stroke, or peripheral vascular disease. We used Cox proportional hazard models to the test the association of each cardiac biomarker with risk of incident atherosclerotic disease, adjusting for multiple possible confounders. When modeled continuously (per SD increase in the log-transformed biomarker), NT-proBNP, hsTnT, GDF-15, and sST2 were significantly associated with incident atherosclerotic disease after adjustment for multiple potential confounders: (NT-proBNP HR, 1.51; 95% CI, 1.27 to 1.81; hsTnT HR, 1.61; 95% CI, 1.38 to 1.89; GDF-15 HR, 1.44; 95% CI, 1.19 to 1.73; and sST2 HR, 1.19; 95% CI, 1.04 to 1.36). NT-proBNP, hsTnT, GDF-15, and sST2 were significantly associated with incident atherosclerotic cardiovascular disease in patients with CKD. These associations may highlight important mechanisms for the development of atherosclerotic disease in CKD.

Embolic versus non- embolic acute coronary syndrome. Prognosis differences

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Coronary embolism (CE) is a rare cause of acute coronary syndrome with current evidence from small case series. In our previous work (n=36), atrial fibrillation was the main risk factor and STEMI the most frequent presentation. Objetives In this analysis we compare severity characteristics, management and in-hospital prognosis between an embolic cohort versus a non-embolic one among patients with left anterior descending artery as culprit vessel. Methods Observational, retrospective descriptive study of patients admitted in our unit from July 2011 to march 2021 for ACS. The diagnosis of CE was established according to the National Cerebral Cardiovascular Center Criteria. Data were obtained from the ARIAM Andalucia Registry. Results 646 Patients were analysed (19 embolic vs 627 non-embolic). There were no differences in ejection fraction (EF) (43±9% vs 44±10%, p&amp;gt;0.05) or Killip-Kimbal (KK) stage at admission moment (stage I more frequent in both groups) or use of inotropes or vasoactive drugs. Embolic cohort had more in-hospital complications: worse KK stage (p=0.001; KKII 23.5% vs 15.3%; KKIII 23.5% vs 5.9%), more thrombocytopenia (5.3% vs 0.8%, p=0.046) and higher hsTnT levels (p=0.000). There was more use of non-invasive mechanical ventilation in embolic group (21.1% vs 4.9%, p=0.002). Without differences in incidence of cardiac arrest, mechanical complications, bradycardia, hemorrhage or in-hospital dead. Conservative management was more frequent in the embolic group. Percutaneous coronary intervention was the most frequent strategy in both cohorts (14.3% vs 3%; 85.6% vs 92.3%; p&amp;lt;0.05). At discharge, there were not significant differences in antithrombotic or anticoagulant therapy. Conclusions In our series the embolic group had worse KK stage and more need of non-invasive mechanical ventilation. They had no significant differences in EF, other mayor complications nor in-hospital mortality.

C-Reactive Protein and High-Sensitive Cardiac Troponins Correlate with Oxidative Stress in Valvular Heart Disease Patients.

Background Valvular heart disease (VHD) is a major contributor to loss of physical function and longevity. Oxidative stress is one of the key causative factors involved in heart disease including VHD. Here, we aimed to illuminate the role and relation of oxidative stress to the VHD risk markers in the human population. Materials and Methods 150 VHD patients and 103 healthy individuals as control were selected for the study and were divided into three groups: the aortic valve, mitral valve, and combined disease based on valvular calcification. Results Our results demonstrated enhanced oxidative stress in the VHD condition, as we found elevated levels of reactive oxygen species (ROS) at the serum, supported by an increased level of thiobarbituric acid reactive substances (TBARs) in the cardiac valvular tissues of the VHD patients. In contrast, we experienced declined antioxidants including Super Oxide Dismutase (SOD), catalase (CAT), and peroxidase (POD) activities. Concurrently, increasing levels of C-reactive protein (CRP), high-sensitivity cardiac troponin I (hs-cTnI), and high-sensitivity cardiac troponin T (hs-cTnT) were detected in the aortic, mitral, and combined disease condition, suggesting a key association of oxidative stress to VHD conditions. Furthermore, regression analysis validated a key association between the impairment of the redox system (ROS and antioxidant enzyme activities) and VHD condition. Conclusion Taken together, dysregulated oxidative stress contributes to the progression of VHD via positively correlating with CRP, hs-TnI, and hs-TnT level.

Correlation Analysis of Plasma Myeloperoxidase Level With Global Registry of Acute Coronary Events Score and Prognosis in Patients With Acute Non-ST-Segment Elevation Myocardial Infarction.

BackgroundMyeloperoxidase (MPO) and global registry of acute coronary events (GRACE) risk scores were independently used to predict adverse outcomes in patients with acute coronary syndrome (ACS). However, the relationship between MPO level and GRACE score, and whether the combination of MPO and GRACE can better predict major adverse cardiovascular events (MACEs) in patients with acute non-ST-segment elevation myocardial infarction (NSTEMI), have not been previously investigated.MethodsA prospective cohort of 271 consecutive patients with NSTEMI were enrolled in this study. Plasma MPO levels were measured by ELISA. Baseline demographic and clinical information was collected, and GRACE scores were calculated at admission. The correlation between MPO and MACEs was evaluated with the GRACE score during a 1-year follow-up.ResultsThe results showed that plasma MPO level was correlated with inflammatory indices (including high-sensitivity C-reactive protein (hs-CRP), leukocyte count, neutrophil count, and fibrinogen), N-terminal pro-B type natriuretic peptide (NT-proBNP), and hypersensitive troponin T (hsTNT) levels (All p-values < 0.05), and there was a statistically significant correlation between plasma MPO level and GRACE score (r = 0.22, p < 0.001). The Kaplan-Meier curves showed that patients with higher MPO levels had lower event-free survival (Log-rank P < 0.001). The multivariate Cox model showed MPO was an independent risk factor for 1-year MACEs in patients with NSTEMI (HR: 3.85, 95% CI: 1.4–10.6, p = 0.009). Subgroup analysis showed that MPO was a strong prognostic biomarker, and its prognostic value was more significant in patients with age >65 years and N-terminal pro-B type natriuretic peptide (NT-proBNP) level >1,000 pg/ml. For high-risk patients with GRACE scores, a higher level of MPO has a higher prognostic value.ConclusionElevated plasma MPO levels are associated with high inflammatory status and GRACE scores in patients with NSTEMI. For high-risk patients with GRACE scores, higher MPO levels were more predictive of future MACEs.

Age-Dependent Reference Values for hs-Troponin T and NT-proBNP and Determining Factors in a Cohort of Healthy Children (The LIFE Child Study)

This study aimed to provide reliable pediatric reference values for N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitive Troponin T (hsTnT) obtained from a population of well children and investigate for associations with sex, pubertal status, body mass index (BMI), and serum lipid levels. We analyzed hsTnT and NT-proBNP values obtained from 4826 samples provided by 2522 children aged 0.25–18 years participating in a prospective longitudinal population-based cohort study, “LIFE child” in Leipzig, Germany (Poulain et al., Eur J Epidemiol 32:145–158, 2017). NT-proBNP values decreased throughout childhood from values over 400 ng/L at 3 months to 138 ng/L in females and 65 ng/L in males by 18 years of age. Values dropped rapidly with advancing pubertal stage. We found a strong association between lower NT-proBNP values and higher BMI or elevated serum lipids, the latter effect being more pronounced in males. For hsTnT levels, approximately half of the measurements were below the detection limit. However, 76% of those aged 3 months and 21% of those aged 6 months had values exceeding the adult cut-off limit. Females had slightly higher levels in the first 2 years of life but this was reversed during puberty. In males, there was an upward trend from pubertal stage 2 onward. We identified a positive association between hsTnT and BMI but a negative association with low-density lipoprotein (LDL) cholesterol and triglyceride levels in boys but not in girls. Based on a large number of healthy children, we have established reliable reference values for NT-proBNP and hsTnT for use in everyday clinical practice. We have also identified important associations between certain metabolic and cardiac markers.Clinical Trial Registration ClinicalTrial.gov (NCT02550236).