Cardiac troponin-T Levels Research Articles

High-Sensitivity Troponin-T and heart failure risk in individuals with suspected acute coronary syndrome

Abstract Background In individuals with suspected acute coronary syndrome (ACS), serial assessments of high-sensitivity cardiac troponin-T (hsTnT) levels demonstrate associations with both short- and long-term mortality and recurrent ischemic events. Nonetheless, the relationship with subsequent heart failure remains inadequately characterized. Purpose We investigated the association between single and serial hsTnT levels and subsequent hospitalization or outpatient medical encounters related to heart failure in individuals presenting with suspected ACS. Methods Utilizing Danish national registries from 2012 to 2019, we identified individuals without known heart failure who underwent dual hsTnT assessments ( 99th percentile upper reference limit: 13.5 ng/l), spaced 1-7 hours apart during hospitalization for myocardial infarction (MI), unstable angina, observation for suspected MI, or chest pain. Participants were categorized based on their hsTnT concentration patterns from the first to the second measurement (primary groups: normal, rising, persistently elevated, or falling) and the extent of hsTnT concentration alterations (secondary groups: <20%, >20 to 50%, or >50% in either direction). Additionally, they were grouped into quartiles based on the initial hsTnT measurement (<=9 ng/l, 10-15 ng/l, 16-66 ng/l, >=67 ng/l) to assess whether heightened hsTnT concentrations correlated with an increased risk of heart failure. Standardized risks of hospitalization or outpatient contacts for heart failure were computed using multivariable logistic regression with average treatment effect modeling. Results The study encompassed 26,835 individuals, of whom 38.9% received discharge diagnoses of MI, 5.1% were diagnosed with unstable angina, and 56.1% with observation for suspected MI or chest pain. Median age was 64.2 years, with 59.5% males. Prevalence of known cardiovascular disease included coronary disease in 18.1% of cases, prior revascularization in 7.2%, atrial fibrillation or flutter in 7.9%, and a history of stroke in 6.3%. Within the initial 30 days, 628 persons received a heart failure diagnosis, with an additional 960 diagnosed between days 31-365. Subjects displaying two normal hsTnT values exhibited the lowest standardized absolute risk (0.39% in days 0-30; 0.58% in days 31-365), while those with persistently elevated concentrations demonstrated the highest risk (6.45% in days 0-30; 7.05% in days 31-365) (Figure). Notably, the magnitude of hsTnT within each primary group did not affect heart failure risk. Conversely, heart failure risk exhibited a positive association with hsTnT concentrations measured in the initial sample. Conclusions In individuals presenting with suspected ACS, subjects with a sustained elevation in hsTnT levels showed the highest risk of subsequent heart failure events. Moreover, a dose-response association was observed between hsTnT concentrations and heart failure risk.Figure

Body temperature, systemic inflammation and risk of adverse events in patients with acute coronary syndromes.

Inflammatory processes can trigger acute coronary syndromes (ACS) which may increase core body temperature (BT), a widely available low-cost marker of systemic inflammation. Herein, we aimed to delineate baseline characteristics of ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation ACS (NSTE-ACS) patients stratified by initial BT and to assess its predictive utility towards major adverse cardiovascular events (MACE) after the index ACS. From 2012 until 2017, a total of 1044 ACS patients, 517 with STEMI and 527 with NSTE-ACS, were prospectively recruited at the University Hospital Zurich. BT was measured by digital tympanic thermometer along with high-sensitivity C-reactive protein (hs-CRP) and cardiac troponin-T (hs-cTnT) levels prior to coronary angiography. Patients were stratified according to initial BT and uni- and multivariable regression models were fit to assess associations of BT with future MACE risk. Among patients with STEMI, BT was not predictive of 1-year MACE, but a U-shaped relationship between BT and MACE risk was noted in those with NSTE-ACS (p = .029), translating into a 2.4-fold (HR, 2.44, 95% CI, 1.16-5.16) increased 1-year MACE risk in those with BT >36.8°C (reference: 36.6-36.8°C). Results remained robust in multivariable-adjusted analyses accounting for sex, age, diabetes, renal function and hs-cTnT. However, when introducing hs-CRP, the BT-MACE association did not prevail. In prospectively recruited patients with ACS, initial BT shows a U-shaped relationship with 1-year MACE risk among those with NSTE-ACS, but not in those with STEMI. BT is a broadly available low-cost marker to identify ACS patients with high inflammatory burden, at high risk for recurrent ischaemic events, and thus potentially suitable for an anti-inflammatory intervention. ClinicalTrials.gov Identifier: NCT01000701.

4-phenylbutyric acid improves sepsis-induced cardiac dysfunction by modulating amino acid metabolism and lipid metabolism via Comt/Ptgs2/Ppara

IntroductionCardiac dysfunction after sepsis the most common and severe sepsis-related organ failure. The severity of cardiac damage in sepsis patients was positively associated to mortality. It is important to look for drugs targeting sepsis-induced cardiac damage. Our previous studies found that 4-phenylbutyric acid (PBA) was beneficial to septic shock by improving cardiovascular function and survival, while the specific mechanism is unclear.ObjectivesWe aimed to explore the specific mechanism and PBA for protecting cardiac function in sepsis.MethodsThe cecal ligation and puncture-induced septic shock models were used to observe the therapeutic effects of PBA on myocardial contractility and the serum levels of cardiac troponin-T. The mechanisms of PBA against sepsis were explored by metabolomics and network pharmacology.ResultsThe results showed that PBA alleviated the sepsis-induced cardiac damage. The metabolomics results showed that there were 28 metabolites involving in the therapeutic effects of PBA against sepsis. According to network pharmacology, 11 hub genes were found that were involved in lipid metabolism and amino acid transport following PBA treatment. The further integrated analysis focused on 7 key targets, including Comt, Slc6a4, Maoa, Ppara, Pparg, Ptgs2 and Trpv1, as well as their core metabolites and pathways. In an in vitro assay, PBA effectively inhibited sepsis-induced reductions in Comt, Ptgs2 and Ppara after sepsis.ConclusionsPBA protects sepsis-induced cardiac injury by targeting Comt/Ptgs2/Ppara, which regulates amino acid metabolism and lipid metabolism. The study reveals the complicated mechanisms of PBA against sepsis.

P.62 Increased skeletal muscle extracellular volume fraction in patients with Becker muscular dystrophy assessed by quantitative magnetic resonance imaging

Quantitative magnetic resonance imaging (MRI) is increasingly proposed in clinical trials related to dystrophinopathies, including Becker muscular dystrophy (BMD). Extracellular volume fraction (ECV) is a candidate variable to characterize muscle tissues microstructure. Previous studies have demonstrated that the myocardium of BMD patients presented increased ECV. Given that cardiac muscle shares important structural features with skeletal muscles, we hypothesize that ECV could also be a sensitive biomarker to monitor pathological alterations of the skeletal muscle structure in BMD patients. We established the sensitivity of ECV quantification using magnetic resonance fingerprinting with water and fat separation (MRF T1-FF) as an imaging biomarker of skeletal muscle tissue alterations in BMD, by comparison with fat fraction (FF) and water relaxation time quantification. Data from the thighs of 28 BMD patients and 8 healthy volunteers were acquired. The MRI exam comprised FF mapping, water T2 mapping and water T1 mapping before and after an intravenous injection of a gadolinium-based contrast agent using MRF T1-FF from which ECV was calculated. Mann-Whitney tests, Kruskal-Wallis tests, ROC curves analysis and Spearman-rank correlation tests were performed. ECV was higher in dystrophic patients than in controls (0.20 [0.16 – 0.28] vs 0.07 [0.06 – 0.07], p<.001). In muscles of BMD patients with normal FF, ECV was also higher than in muscles of healthy controls (0.11 [0.10 – 0.13] vs 0.07 [0.06 – 0.09], p<.001). ECV classified dystrophic muscles with high sensitivity and specificity (AUC, 0.98; 95%CI: 0.96-0.99, p <.001), and correlated significantly with FF (ρ = .62, p < .001), water T2 (ρ = .56, p = .002), Walton score (ρ = .58, p = .001) and serum cardiac troponin-T level (ρ = .63, p < .001). In conclusion, muscle ECV measured with MRF represents a promising imaging biomarker for the early detection of skeletal muscle involvement in patients with Becker muscular dystrophy.

Effect of thymoquinone on sepsis-induced cardiac damage via anti-inflammatory and anti-apoptotic mechanisms.

ObjectiveSepsis is a systemic and deleterious host reaction to severe infection. Cardiac dysfunction is an established serious outcome of multiorgan failure associated with this condition. Therefore, it is important to develop drugs targeting sepsis-induced cardiac damage and inflammation. Thymoquinone (TQ) has anti-inflammatory, anti-oxidant, anti-fibrotic, anti-tumor, and anti-apoptotic effects. This study examined the effects of thymoquinone on sepsis-induced cardiac damage.MethodsMale BALB/c mice were randomly segregated into four groups: control, TQ, cecal ligation and puncture (CLP), and CLP + TQ groups. CLP was performed after gavaging the mice with TQ for 2 weeks. After 48 hours, we estimated the histopathological changes in the cardiac tissue and the serum levels of cardiac troponin-T. We evaluated the expression of factors associated with inflammation, apoptosis, oxidative stress, and the PI3K/AKT pathway.ResultsTQ significantly reduced intestinal histological alterations and inhibited the upregulation of interleukin-6, tumor necrosis factor-α, Bax, NOX4, p-PI3K, and p-AKT. TQ also increased Bcl-2, HO-1, and NRF2 expression.ConclusionThese results suggest that TQ effectively modulates pro-inflammatory, apoptotic, oxidative stress, and PI3K/AKT pathways, making it indispensable in the treatment of sepsis-induced cardiac damage.

Levels of cardiac troponin-T and LDL-C to HDL-C ratio of hospitalized COVID-19 patients: A case-control study

Background: People with coronavirus disease 2019 (COVID-19) are frequently at higher risk of developing cardiovascular and metabolic disorders, which are strongly related to the development of long-term illness and higher mortality. These effects may be caused by several interrelated processes, including the IL-6 driven cytokine storm or uncontrolled angiotensin II stimulation. In addition, the direct viral infection of cardiac myocytes is thought to cause cardiac injury because it increases metabolic demand, activates the immune system, and causes vasculature disruption. The objective of this study was to determine whether there is a relationship between cardiac troponin-T (cTnT) and low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol (HDL-C) ratio values with COVID-19. Methods: During the data collection stage, 90 participants were included, 45 healthy controls and 45 hospitalized patients diagnosed with COVID-19 using reverse transcription-quantitative PCR (RT-qPCR). Each participant provided 5 ml venous blood to begin analyzing cTnT and LDL-C:HDL-C ratio levels in their blood to see whether there is an association between the level of any of these markers and COVID-19 infection using SPSS version 23. Results: This research reported a significant rise in the measured values of cTnT and LDL-C:HDL-C ratio in patients' blood compared to controls, with P-values of 0.025 and 0.000, respectively, in which alpha values &lt; 0.05, These biomarkers hold the promise in predicting COVID-19 severity, and early treatment may help reduce complications. Conclusions: Due to the fact that cTn is a diagnostic marker of disease activity and a strong independent predictor of negative events, its usage in emergency rooms may well be advantageous. If cTn is elevated, hospitalization may be indicated. A difference in the blood LDL-C:HDL-C ratio of COVID-19 patients demonstrated an association with the illness. Because lipid studies are inexpensive and reliable to do, they may aid clinicians in identifying the severity of COVID-19.

Compatibility and function of human induced pluripotent stem cell derived cardiomyocytes on an electrospun nanofibrous scaffold, generated from an ionomeric polyurethane composite.

Synthetic scaffolds are needed for generating organized neo-myocardium constructs to promote functional tissue repair. This study investigated the biocompatibility of an elastomeric electrospun degradable polar/hydrophobic/ionic polyurethane (D-PHI) composite scaffold with human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The composite material was electrospun to generate scaffolds, with nanofibres oriented in aligned or random directions. These features enabled the authors to evaluate the effect of characteristic elements which mimic that of the native extracellular matrix (alignment, chemical heterogeneity, and fiber topography) on hiPSC-CMs activity. The functional nature of the hiPSC-CM cultured on gelatin and Matrigel-coated scaffolds were assessed, investigating the influence of protein interactions with the synthetic substrate on subsequent cell phenotype. After 7 days of culture, high hiPSC-CM viability was observed on the scaffolds. The cells on the aligned scaffold were elongated and demonstrated aligned sarcomeres that oriented parallel to the direction of the fibers, while the cells on random scaffolds and a tissue culture polystyrene (TCPS) control did not exhibit such an organized morphology. The hiPSC-CMs cultured on the scaffolds and TCPS expressed similar levels of cardiac troponin-T, but there was a higher expression of ventricular myosin light chain-2 on the D-PHI composite scaffolds versus TCPS, indicating a higher proportion of hiPSC-CM exhibiting a ventricular cardiomyocyte like phenotype. Within 7 days, the hiPSC-CMs on aligned scaffolds and TCPS beat synchronously and had similar conductive velocities. These preliminary results show that aligned D-PHI elastomeric scaffolds allow hiPSC-CMs to demonstrate important cardiomyocytes characteristics, critical to enabling their future potential use for cardiac tissue regeneration.

Role of cardiac biomarkers in patients of chronic obstructive pulmonary disease with acute exacerbation

Background: Patients with chronic obstructive pulmonary disease (COPD) often have cardiovascular comorbidities. Patients of COPD with cardiovascular complications tend to have more symptoms and a higher mortality than do patients with COPD alone. There are several cardiac biomarkers such as Troponin-T, creatine phosphokinase-MB (CPK-MB), and N-terminal pro-brain natriuretic peptide (NT-proBNP) which can be used to detect cardiac dysfunction in patients of COPD. Retrospective studies suggest that plasma levels of NT-proBNP and cardiac Troponin-T are often elevated in patients with acute exacerbations of COPD and are associated with increased mortality. Aims and objectives: In this study, we assessed the presence of cardiac dysfunction in patients presenting with acute exacerbation of COPD (AECOPD) by using cardiac biomarkers proBNP, Troponin-T, and CPK-MB. Patients were followed up for 30 days to know the relationship between cardiac dysfunction and outcome in terms of repeated admissions, intensive care units (ICU) admissions, and/or mortality. Methodology: Ninety patients of AECOPD were enrolled in our study. A detailed history was taken and physical examination performed in these patients. All patients in the study were subjected to hematological and biochemical investigations. ProBNP, Troponin-T, and CPK-MB were measured within 48 h of admission as measure of cardiac dysfunction; and outcome was assessed in terms of mortality, ICU admission, and repeated admissions within 30 days of admission. Results: Among the study population, 77.77% had at least one deranged cardiac biomarker, and 18.88% of populations had all the three biomarkers of cardiac dysfunction deranged. 24 out of the 90 participants required ventilatory support in the form of noninvasive or invasive ventilation. 7.14% of the study population had repeated admissions, 24.28% had ICU admissions and 11.43% had mortality. All of them had deranged cardiac biomarkers. There was a significant association between deranged proBNP and ICU admission and mortality (P = 0.0151 and 0.0217, respectively). COPD was more prevalent in the age group of 50–70 years and in males. ProBNP levels were significantly elevated in patients who required ventilatory support (P = 0.003). Conclusions: Cardiac dysfunction is common during exacerbations of COPD and portends a poor prognosis. Cardiac dysfunction was more prevalent in the elderly. Patients with deranged cardiac biomarkers had a greater number of ICU admissions, repeated hospital admissions, and a higher mortality. In the follow-up, elevated proBNP was found to be a strong marker for predicting ICU admission, mortality, and repeated admissions.

Electrocardiographic and histopathological characterizations of diabetic cardiomyopathy in rats.

Diabetes is a clinical condition that is associated with insulin deficiency and hyperglycemia. Cardiomyopathy, retinopathy, neuropathy, and nephropathy are well known complications of the elevated blood glucose. Diabetic cardiomyopathy is a clinical disorder that is associated with systolic and diastolic dysfunction along with cardiac fibrosis, inflammation, and elevated oxidative stress. In this study, diabetes was induced by intraperitoneal injection of streptozotocin (STZ) 50mg/kg. We determined the plasma levels of cardiac troponin-T (cTnT) and creatinine kinase MB (CK-MB) by ELISA. Diabetic rats showed abnormal cardiac architecture and increased collagen production. Significant elevation in ST-segment, prolonged QRS, and QT-intervals and increased ventricular rate were detected. Additionally, diabetic rats showed a prolongation in P wave duration and atrial tachyarrhythmia was observed. Plasma levels of cTnT and CK-MB were elevated. In conclusion, these electrocardiographic changes (elevated ST-segment, prolonged QT interval, and QRS complex, and increased heart rate) along with histopathological changes and increased collagen formation could be markers for the development of diabetic cardiomyopathy in rats.

Abstract 11994: Proteomic Evaluation And Biomarker Identification In Tricuspid Regurgitation

Introduction: Not only are mechanisms involved in tricuspid regurgitation (TR) incompletely understood, there is no established means of risk stratification for patients undergoing tricuspid valve interventions. A better understanding of underlying biological mechanisms allows for identification of therapeutic targets as well as biomarkers for disease staging, monitoring, and prediction following intervention. Methods: Preoperatively, 276 patients undergoing tricuspid annuloplasty, divided into training and validation cohorts, were assessed and followed-up for adverse events defined as death or heart failure requiring hospitalisation. Preoperative plasma samples were analysed for levels of cardiac troponin-T, NTproBNP, as well as 91 other markers (Olink multiplex assay). Correlated network analysis was used for clustering plasma markers. The relations of clusters to echocardiographic parameters and adverse outcomes were assessed by linear and Cox regression respectively. Pathway overrepresentation analysis was conducted to ascertain biological mechanisms overrepresented in relevant clusters by enrichment with reference to existing knowledge. Results: Over a median follow-up period of 3.7 years, 83 adverse events occurred. Two clusters of biomarkers in the training cohort significantly correlate with right chamber and tricuspid annular dilatation, regurgitant jet area, effective regurgitant orifice area and/or adverse outcomes following tricuspid annuloplasty (P&lt;0.05). The two clusters are represented by hub proteins TNF Receptor Superfamily Member 10A and TRAIL receptor 2. Overrepresented biological pathways in the two clusters include immunological responses, cytokine production regulation, and responses to lipids. Both clusters are conserved in the validation cohort. Conclusion: Immunoinflammatory pathways may be implicated in tricuspid regurgitation, and markers related to such pathways show prognostic significance.

Molecular ratio of mature B-type natriuretic peptide in acute heart failure: an indicator for ventricular contractile recovery.

AimsThe methodology to distinguish between the heart failure (HF) with recovered ejection fraction (HFrecEF) and those with continuously reduced ejection fraction (EF) (HFcrEF) on admission has not been established. We recently demonstrated that the ratio of plasma levels of pro‐B‐type natriuretic peptide (proBNP) to total BNP (proBNP plus mature BNP) is decreased on admission in patients with mild acute HF, but not in severe acute HF as a compensatory mechanism for activating cyclic GMP via increases of bioactive mature BNP. We aimed to test the hypothesis that the ratio of bioactive mature BNP to total BNP is associated with reverse remodelling capacity in patients with HF with reduced EF.Methods and resultsPlasma proBNP and total BNP were measured in patients with acute decompensated HF by using specific and sensitive enzyme immunochemiluminescent assay. Estimated percent mature BNP (%emBNP) was calculated as ([total BNP − proBNP]/total BNP) × 100. We retrospectively identified the patients with reduced EF (≤40%, on admission) who had echocardiographic data after discharge (n = 93). We defined patients with increased EF by >10% during the follow‐up term (median, 545 days) after the admission as HFrecEF group. We compared patient characteristics, %emBNP, and other biomarkers between HFrecEF and HFcrEF. Of the enrolled patients with HFrecEF (n = 32) and HFcrEF (n = 61), on admission, %emBNP was significantly higher in HFrecEF than in HFcrEF (44.1% vs. 36.9%; P < 0.05). There were no significant differences in left ventricular EF on admission between the two groups. The univariate analysis revealed that %emBNP on admission was associated with HFrecEF occurrence rate (P < 0.05), in contrast both total BNP and high‐sensitive cardiac troponin‐T levels were not associated with HFrecEF occurrence rate.ConclusionsThe ratio of mature BNP to total BNP in plasma at the time of hospital admission may be predictive of left ventricular contractile recovery. Preservation of the capacity to convert proBNP to mature BNP, but not myocardial injury itself, is associated with future ventricular contractile recovery.

Original Research: Long-Term Prognosis After ST-Elevation Myocardial Infarction in Patients with a Prior Cancer Diagnosis.

IntroductionIt is unknown how long-term prognosis after ST-elevation myocardial infarction (STEMI) in patients with a prior cancer diagnosis is impacted by cancer-related factors as diagnosis, stage, and treatment. We aimed to assess long-term survival trends after STEMI in this population to evaluate both cardiovascular and cancer-related drivers of prognosis over a follow-up period of 5 years.MethodsIn this retrospective single-center cohort study, patients with a prior cancer diagnosis admitted with STEMI between 2004 and 2014 and treated with primary percutaneous coronary intervention (PCI) were recruited from the STEMI clinical registry of our institution.ResultsIn the 211 included patients, the cumulative incidence of all-cause death after 5 years of follow-up was 38.1% (N = 60). The cause of death was predominantly malignancy-related (N = 29, 48.3% of deaths) and nine patients (15.0%) died of a cardiovascular cause. After correcting for age and sex, a recent cancer diagnosis (< 1 year relative to > 10 years, HRadj 2.98 [95% CI: 1.39–6.41], p = 0.005) and distant metastasis at presentation (HRadj 4.02 [1.70–9.53], p = 0.002) were significant predictors of long-term mortality. While maximum levels of cardiac troponin-T and creatinine kinase showed significant association with mortality (resp. HRadj 1.34 [1.08–1.66], p = 0.008; HRadj 1.36 [1.05–1.76], p = 0.019), other known determinants of prognosis after STEMI, e.g., hypertension and renal insufficiency, were not significantly associated with survival.ConclusionsPatients with a prior cancer diagnosis admitted with STEMI have a poor survival rate. However, when the STEMI is optimally treated with primary PCI and medication, cardiac mortality is low, and prognosis is mainly determined by factors related to cancer stage.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40119-021-00244-4.

Perfluorooctane sulfonate induces heart toxicity involving cardiac apoptosis and inflammation in rats.

Perfluorooctane sulfonate (PFOS) is a persistent pollutant that exerts toxicity and induces cardiogenesis in humans and animals. Yet, the effect of PFOS exposure on cardiac toxicity in adult rats has, to our knowledge, not been reported and the mechanism still remains unknown. The present study aimed to investigate the toxicity of PFOS on rat hearts and any associated mechanisms. Rats were exposed to 0 (control), 1 and 10 mg/kg PFOS every other day for 14 days. Body weight and heart weight were recorded. The serum levels of lactic dehydrogenase (LDH), creatine kinase (CK), creatine kinase-isoenzyme-MB (CK-MB) and cardiac troponin-T (cTn-T) in heart tissues were measured using biochemical assays. TUNEL staining and western blotting were applied to analyze levels of apoptosis in rat hearts. Pathological assessment and immunohistochemistry analysis of heart tissues were used to evaluate the levels of PFOS-induced cardiotoxicity and inflammatory infiltration. PFOS exposure at the dosage of 10 mg/kg significantly increased the percentage of heart to body weight; however, it did not alter the body weight. At 10 mg/kg, PFOS significantly increased expression levels of myocardial injury markers, such as cTn-T, LDH, CK and CK-MB, while 1 mg/kg PFOS upregulated the expression level of cTn-T in rats. Notably, cardiac fibrosis and myocardiac hypertrophy appeared in the 10 mg/kg PFOS group. In addition, TUNEL-positive cells were significantly increased by exposure to 10 mg/kg PFOS in rat heart tissues. The protein expressions profiles of p53 and Bax were also significantly upregulated in the 10 mg/kg PFOS group. Inflammatory infiltration, detected by anaylzing expression levels of IL-1β and TNF-α, was significantly raised by 10 mg/kg PFOS exposure. In conclusion, these results demonstrated that 10 mg/kg PFOS-induced cardiac toxicity in rats, which was associated with an increase in apoptosis and the expression of proinflammatory cytokines.

Masywna zatorowość płucna u 33-letniego mężczyzny ze słabymi czynnikami ryzyka do żylnej choroby zakrzepowo-zatorowej – postępowanie według wytycznych ESC

We present a case of a 33-year-old obese patient with pulmonary embolism (PE), admitted to the hospital with gradually worsening of dyspnea, general malaysia, right lower limb redness and oedema. During examination tachycardia (124/min) and hypoxemia (90% SpO2) were recorded. Laboratory findings revealed elevated levels of D-dimer, cardiac troponin-T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP). Electrocardiography showed clear signs of pulmonary embolism – SIQIIITIII and T-waves inversion in V1-V5. Diagnosis prediction was strengthened by transthoracic echocardiography, which uncovered signs of right ventricle overload and 60/60 sign. Despite little risk factors of venous thromboembolism (VTE), patient was assessed to high clinical probability of PE according to revised Geneva clinical prediction rule. Predisposing condition to VTE could be past COVID-19 infection. Patient was categorized into a group of intermediate-high risk of early mortality, received parenteral anticoagulation with unfractionated heparin and underwent computed tomography pulmonary angiography (CTPA) (class IB), which confirmed the diagnosis in this almost certain case. CTPA can cause many side-effects, including: contrast-induced nephropathy or anaphylaxis, which in such unequivocal situation may be questioned and other, safer methods of PE confirmation could prove their usefulness.

High-Sensitivity Troponin for Suspected Acute Coronary Syndrome in Patients With Chronic Kidney Disease Versus Patients Without Chronic Kidney Disease.

BackgroundHeart disease is the leading cause of death in the United States. Patients with acute coronary syndrome (ACS) who have chronic kidney disease (CKD) have a twofold increase in mortality compared to patients with normal kidney function. Patients with CKD tend to have elevated baseline high-sensitivity cardiac troponin-T (hs-cTnT) levels. We studied patients with or without CKD to find out if a higher baseline hs-cTnT influenced the change in hs-cTnT (delta) when ruling in or ruling out ACS.MethodsEighty-nine patients were included in this study (29 with CKD; 60 without CKD). Delta hs-cTnT was dichotomized based on those who had delta of ≥ 5, or < 5. We calculated the positive predictive values, negative predictive values, sensitivities and specificities. Shapiro-Wilk test and independent t-test were used for the continuous variables. Mann-Whitney U test was used to examine the variables between the two groups. Chi-square test was used to compare the categorical variables between the two groups.ResultsThe mean ages of patients with CKD and without CKD were 61.2 and 58.9 years, respectively (P = 0.508). We found that although there were differences in the sensitivities, specificities, positive predictive values and negative predictive values of delta hs-cTnT > 5 for ACS between the patients with CKD and without CKD, the differences were not statistically significant. Subgroup analysis showed that in patients with CKD, the positive predictive values and sensitivities of delta hs-cTnT > 5 for CAD requiring percutaneous coronary intervention (PCI) and stent were significantly higher compared to the patients without CKD (82.4% vs. 27.3%, and 82.4% vs. 40.0%, respectively) (P < 0.05).ConclusionsIn calculating delta hs-cTnT to rule in or rule out ACS, the presence of CKD does not influence the delta. Patients with CKD and a delta hs-cTnT > 5 have significantly higher risk of undergoing PCI.

Corrected QT interval prolongation: A new predictor of cardiovascular risk in patients with non-St-elevation acute coronary syndrome. Algerian cohort

Recently we reported that prolongation of the corrected QT (CTc) interval is an independent risk factor in patients with unstable angina and acute ischemic changes. The aim of this study was to determine the prognostic value of the corrected QT (CTc) interval in patients with non-ST-segment elevation acute coronary syndrome who do not exhibit acute ischemic changes on admission ECG. The study included 195 patients with this syndrome. On admission, a standard 12-lead ECG was recorded, the cardiac troponin-T was measured and aTIMI (Thrombolysis in Myocardial Infarction) risk score was calculated. The primary endpoint was the combination of nonfatal acute myocardial infarction, percutaneous or surgical revascularization, and cardiac death up to 30 days after discharge. Two independent investigators measured the QT interval manually and the corrected value was derived using Bazett's formula. In the statistical analysis, the following cut-off points were used: the median TIMI risk score, a cardiac troponin-T level of 0.04 ng/mL, and a QTc of 0.458 s. Of the 74 patients (38%) who reached the primary endpoint, 59 (80%) had QTc prolongation. Binary logistic regression analysis showed that QTc prolongation was an independent predictor of the combined endpoint. This study shows that QTc prolongation is an independent predictor of cardiovascular risk in patients with non-ST-segment elevation acute coronary syndrome but without acute ischemic changes on admission ECG.

Physiological and Metabolic Responses of Amateur Spinal Cord Injured Wheelchair Racers Participating in a Marathon: A Pilot Observational Study.

ABSTRACTObjectives:We analyzed exercise-related changes in cardiac troponins and other physiological and metabolic parameters in amateur wheelchair racers with spinal cord injury (SCI) participating in a marathon event.Methods:This pilot, prospective, observational study was conducted at a community marathon event. Fifteen community-living individuals with SCI who had registered to participate in the marathon were recruited for the study. Participants with SCI used manually propelled wheelchairs (n=5) or tricycles (n=10). The outcome measures were high-sensitivity cardiac troponin-T levels (hs-cTnT), heart rate, and metabolic parameters, including body temperature, serum electrolytes, and urine osmolality. These parameters were compared with 15 age- and race-distance-matched non-SCI runners who participated in the same marathon.Results:Participants with SCI had a higher median (inter-quartile range) baseline hs-cTnT level [13.7 ng/L (10.3–25)] than did runners [4.2 ng/L (3.2–8.7; P <0.001)]. Post-race values of hs-cTnT were elevated in participants with SCI [28.0 ng/L (19.0–48.2)] and in runners [41.5 ng/L (18.4–87.1, P= 0.7)]; however, there was no significant difference between the two groups. Other parameters were not significantly different between SCI participants and runners.Conclusion:Post-race hs-cTnT levels of amateur SCI participants were elevated but were not significantly different from those of runners. Other race-induced physiological and metabolic changes in SCI participants were comparable to those of runners. The high baseline hs-cTnT levels in participants with SCI observed in this study warrant further research.

Abstract 14182: Genome Wide Association Study for High Sensitive Cardiac Troponin T Levels Identifies a Novel Gene in Europeans With Type 1 Diabetes

Introduction: Adults with diabetes have a two to four folds increased risk of dying with heart disease compared to those without diabetes. Higher cardiac troponins, especially Troponin T (TnT) is a specific biomarker for cardiac injury also guiding management of chest pain and associated with increased risk of heart failure. Hypothesis: There is limited knowledge on genes regulating cardiac TnT levels. We conducted a genome wide association study (GWAS) for circulating cardiac TnT levels among individuals with type 1 diabetes (T1D). Methods: The study included 849 T1D individuals recruited from the outpatient clinic at Steno Diabetes Center Copenhagen, Denmark. Serum high sensitive TnT (hsTnT) levels were measured and log transformed for normalization after check for outliers (mean ± 4 SD). Genotyping on 538,448 single nucleotide variants (SNVs) was done using Illumina Human Core Exome Chip. After quality control filters: hardy weinberg equilibrium (p &gt;10 -6 ), European ancestry, genotype call rates &gt;95%, common variants were examined in 740 individuals with hs TnT data. We ran linear regression based additive genetic models adjusting for age, sex, diabetes duration and population sub structure using Plink and R statistical programs. P &lt;5 x 10 -8 was genome wide significant (GWS) while 5 x 10 -8 &lt; p &lt; 1 x 10 -6 was considered suggestive. Results: Participants had a mean (SD) age of 43.7 (11.1) years, 57.4% were men, with diabetes duration of 28.0 (9.5) years, HbA1c 8.9 (1.3) % and 50.5% with diabetic nephropathy. Median (IQR) hsTnT levels were 64.7 (29.2-175.6) pg/ml. We identified a GWS missense common variant in the CISD3 gene locus on chromosome 17 (p=1.7 x 10 -8 ) for cardiac hsTnT levels. This gene codes CDGSH Iron Sulfur Domain 3 protein also called Mitochondrial Inner NEET Protein. Two suggestive loci were PTPRD (Protein Tyrosine Phosphatase Receptor Type D; p=4.9 x 10 -7 ) and DCC (DCC Netrin 1 Receptor; 6.6 x 10 -7 ) on chromosomes 9 and 18. PTPRD is a known GWS locus for hsTnT that we reconfirm among T1D individuals. Conclusions: We identify a novel gene locus for circulating cardiac hsTnT levels among T1D individuals of European ancestry. CISD3 is expressed in heart tissue regulating mitochondrial functions. Further validation is suggested.

Abstract 13919: Race and Gender Specific High Sensitivity Troponin-t Cutoff Values Improve Detection in Patients’ With Ischemic Heart Disease

Introduction: Death rates from acute coronary syndrome events (ASCE) are 30% higher in African Americans than in Caucasians. A potential reason for this disparity is the underdiagnosis of ACSE due to race-specific differences in blood levels of cardiac troponin-T (cTnT), the biomarker of choice for the exclusion of myocardial injury. Hypothesis: Race- and gender-specific high-sensitivity cTnT (hs-cTnT) cutoff values will improve the detection of myocardial injury. Methods: Emergency Department encounters at the University of Chicago from June 2018 through April 2019 with at least 1 hs-cTnT value were included. Race- and gender-specific 99 th percentiles for hs-cTnT were determined for patients without a history of hypertension, heart failure, coronary artery disease, diabetes, or chronic kidney disease, and used as the threshold for a positive result. These threshold values were compared against manufacturer’s recommended gender-only values (male ≥ 22 ng/dL, female ≥ 14 ng/dL). Confusion matrices were used to calculate test characteristics. The presence of ischemic heart disease was determined by the corresponding International Statistical Classification of Diseases. Results: Among 10,934 included encounters, 89.9% were African American. The 99 th percentile values for African American were lower than for matched white counterparts. Race and gender specific cutoffs had higher specificity (83.1% vs 75.2%), greater positive predictive value (91.9% vs 90.7%), and lower false negative rates (16.9% vs. 24.8%) compared with traditional gender-only cutoff values. During the 10 months of data collection, race- and gender-specific cutoffs would have correctly identified 215 additional encounters as having ischemic heart disease, all of them African Americans. The net reclassification rate was +7.91%. Conclusions: Using race-specific, in addition to traditional gender-specific, hs-cTnT cutoff values resulted in higher specificity, greater positive predictive value, and lower false negative rates. Nearly 8% of patients with eventual diagnosis of ischemic heart disease would have been correctly reclassified using race- and gender-specific cutoffs. These findings suggest that race- and gender-specific cutoffs should be further explored.

Serum high-density lipoprotein cholesterol serves as a prognostic marker for light-chain cardiac amyloidosis

BackgroundOxidative stress and inflammation are central in the pathophysiology of light-chain amyloid cardiomyopathy (AL-CM). High-density lipoprotein cholesterol (HDLC) is an antioxidant and acts as an anti-inflammatory regulator. In this study, the prognostic value of serum HDL-C was explored in AL-CM. MethodIn this prospective single-center study, two hundred consecutive patients with biopsy-confirmed light-chain amyloidosis (AL) and cardiac involvement were enrolled. Patients were classified into low or normal serum HDL-C groups (HDL-C < 40 mg/dL and HDL-C ≥ 40 mg/dL, respectively). Univariate and multivariate Cox models were used to identify predictors of survival. Kaplan-Meier analysis was performed to compare survival between patients with low or normal serum HDL-C. ResultsPatients with low serum HDL-C were more likely to present with higher levels of cardiac troponin-T (123.4 ng/L vs. 79.1 ng/L, p = 0.026) and higher levels of N-terminal pro-B-type natriuretic peptide (9146 pg/mL vs. 4945 pg/mL, p = 0.011). Patients were followed for a median follow-up period of 19 months, in which 118 (59%) patients died. The median overall survival times for patients with low or normal serum HDL-C were 7 and 16 months, respectively (p = 0.002). Multivariate analysis demonstrated that serum HDL-C (HR 0.984, 95% CI 0.973–0.994, p = 0.003) was independently associated with prognosis, after adjusting for nephrotic syndrome, hepatic involvement, nutritional state, renal function, SBP, DBP, serum uric acid, total cholesterol, Mayo AL 2004 stage, and treatment with chemotherapy. ConclusionsHDL-C is a novel serum biomarker for disease severity and prognosis in light-chain cardiac amyloidosis.