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Introduction: Risk stratification scores such as the European Systematic COronary Risk Evaluation (SCORE) are used to guide individuals on cardiovascular disease (CVD) prevention. Adding high-sensitivity troponin I (hsTnI) to such risk scores has the potential to improve accuracy of CVD prediction. We investigated how applying hsTnI in addition to SCORE may impact management, outcome, and cost-effectiveness. Methods: Characteristics of 72,190 apparently healthy individuals from the Biomarker for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project were included into a discrete-event simulation comparing two strategies for assessing CVD risk. The standard strategy reflecting current practice employed SCORE (SCORE); the alternative strategy involved adding hsTnI information for further stratifying SCORE risk categories (S-SCORE). Individuals were followed over ten years from baseline examination to CVD event, death or end of follow-up. The model tracked the occurrence of events and calculated direct costs of screening, prevention, and treatment from a European health system perspective. Cost-effectiveness was expressed as incremental cost-effectiveness ratio (ICER) in € per quality-adjusted life year (QALYs) gained during 10 years of follow-up. Outputs were validated against observed rates, and results were tested in deterministic and probabilistic sensitivity analyses. Results: S-SCORE yielded a change in management for 10.0% of individuals, and a reduction in CVD events (4.85% vs. 5.38%, p<0.001) and mortality (6.80% vs. 7.04%, p<0.001). S-SCORE led to 23 (95%CI: 20–26) additional event-free years and 7 (95%CI: 5–9) additional QALYs per 1,000 subjects screened, and resulted in a relative risk reduction for CVD of 9.9% (95%CI: 7.3–13.5%) with a number needed to screen to prevent one event of 183 (95%CI: 172 to 203). S-SCORE increased costs per subject by 187€ (95%CI: 177 € to 196 €), leading to an ICER of 27,440€/QALY gained. Sensitivity analysis was performed with eligibility for treatment being the most sensitive. Conclusion: Adding a person's hsTnI value to SCORE can impact clinical decision making and eventually improves QALYs and is cost-effective compared to CVD prevention strategies using SCORE alone. Stratifying SCORE risk classes for hsTnI would likely offer cost-effective alternatives, particularly when targeting higher risk groups. [ABSTRACT FROM AUTHOR]

Background: Lipoproteins in cell membranes are related to membrane stability and play a role against microorganisms. Patients with COVID-19 often experience myocyte membrane damage. Objective: This study aimed to search the relationship of atherogenic indices with myocardial damage and mortality in COVID-19. Methods: This was an observational, single-center, retrospective study. The study population was grouped according to in-hospital mortality. C-reactive protein (CRP), CRP to albumin ratio (CAR), monocyte to high density lipoprotein cholesterol ratio (MHR), levels of total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol (HDLc), and low-density lipoprotein cholesterol (LDLc) and cardiac troponin I (cTnI) were recorded. Atherogenic indices (plasma atherogenic index [AIP], atherogenic coefficient [AC], Castelli's risk indices I and II [CRI I and II], triglyceride to HDLc ratio (THR) were calculated. Results: A total of 783 patients were included. The mortality rate was 15.45% (n = 121). The median age of non-survivor group (NSG) was higher than survivor group (SG) [66.0 years (Q1 –Q3: 55.0–77.5) vs 54.0 years (Q1 –Q3: 43.0–63.0)] (p < 0.001). Study parameters which were measured significantly higher in the NSG were CRP, cTnI, triglyceride, CRI-I, CRI-II, AC, AIP, ferritin, CAR, MHR and THR. LDLc, HDLc, TC and albumin were significantly lower in NSG (p<0.001). Conclusion: THR is positively correlated with myocardial damage and strongly predicts in-hospital mortality in COVID-19. [ABSTRACT FROM AUTHOR]

Cardiac troponin I (cTnI) is a cardiac biomarker for diagnosing ischemic heart disease and acute myocardial infarction. Current biochemical assays use antibodies (Abs) due to their high specificity and sensitivity. However, there are some limitations, such as the high-cost production of Abs due to complex instruments, reagents, and steps; the variability of Abs quality from batch to batch; the low stability at high temperatures; and the difficulty of chemical modification. Aptamer overcomes the limitations of antibodies, such as relatively lower cost, high reproducibility, high stability, and ease of being chemically modified. Aptamers are three-dimensional architectures of single-stranded RNA or DNA that bind to targets such as proteins. Six aptamers (Tro1-Tro6) with higher binding affinity than an antibody have been identified, but the molecular interaction has not been studied. In this study, six DNA aptamers were modeled and docked to cTnI protein. Molecular docking revealed that the interaction between all aptamer and cTnI happened in the similar cTnI region. The interaction between aptamer and cTnI involved hydrophobic interaction, hydrogen bonds, π-cation interactions, π-stack interactions, and salt-bridge formation. The calculated binding energy of all complexes was negative, which means that the complex formation was thermodynamically favorable. The electrostatic energy term was the main driving force of the interaction between all aptamer and cTnI. This study could be used to predict the behavior of further modified aptamer to improve aptamer performance. [ABSTRACT FROM AUTHOR]

The early unfractionated heparin (UFH) treatment in patients with ST-elevation myocardial infarction (STEMI) is a single-center, open-label, randomized controlled trial. The study population are patients with STEMI that undergo primary percutaneous coronary intervention (PPCI). The trial was designed to investigate whether early administration of unfractionated heparin immediately after diagnosis of STEMI is beneficial in terms of patency of infarct-related coronary artery (IRA) when compared to established UFH administration at the time of coronary intervention. The patients will be randomized in 1:1 fashion in one of the two groups. The primary efficacy endpoint of the study is Thrombolysis in myocardial infarction (TIMI) flow grades 2 and 3 on diagnostic coronary angiography. Secondary outcome measures are: TIMI flow after PPCI, progression to cardiogenic shock, 30-day mortality, ST-segment resolution, highest Troponin I and Troponin I values at 24 hours. The safety outcome is bleeding complications. The study of early heparin administration in patients with STEMI will address whether pretreatment with UFH can increase the rate of spontaneous reperfusion of infarct-related coronary artery. [ABSTRACT FROM AUTHOR]

Objective: Interleukin 34 (IL-34) is a molecule whose expression is increased in conditions such as autoimmune disorders, inflammation, and infections. Our study aims to determine the role of IL-34 in the diagnosis, follow-up, and prognosis of Coronavirus Disease-19 (COVID-19). Method: A total of 80 cases were included in the study as 40 COVID-19 positive patient groups and 40 COVID-19 negative control groups. The COVID-19-positive group consisted of 20 intensive-care unit (ICU) patients and 20 outpatients. Serum IL-34, c-reactive protein (CRP), ferritin, D-dimer, troponin I, hemogram, and biochemical parameters of the cases were studied and compared between groups. Results: IL-34 levels were significantly higher in the COVID-19-positive group than in the negative group. IL-34 levels increased in correlation with CRP in predicting the diagnosis of COVID-19. IL-34 levels higher than 31.75 pg/m predicted a diagnosis of COVID-19. IL-34 levels did not differ between the outpatient and ICU groups in COVID-19-positive patients. IL-34 levels were also not different between those with and without lung involvement. Conclusion: While IL-34 levels increased in COVID-19-positive patients and were successful in predicting the diagnosis of COVID-19, it was not found to be significant in determining lung involvement, risk of intensive care hospitalization, and prognosis. The role of IL-34 in COVID-19 deserves further evaluation. [ABSTRACT FROM AUTHOR]

Background: The cardiac stress for veteran football players during match is considerable. In this specific elderly population, the kinetics of exercise-induced cardiac troponin I (cTnI) and B-Type natriuretic peptide (BNP) could potentially be related to cardiovascular risk factors (CVRF) and cardiovascular disease and are therefore be investigated for their usefulness as an complement to established screening measures. Methods: cTnI and BNP was measured in 112 veteran football players (age: 51 ± 10 years) within 30 minutes pre- and post-match. Players with elevated cTnI (cTnI-positive) and a control group (out of the 112 veteran players) with normal cTnI (cTnI-negative) underwent cardiac follow-up 4.2 ± 3.5 months post-match, comprising history, resting and stress ECG (including 30 minutes pre- and post cTnI and BNP), and echocardiography. Results: In 33 players (29%) cTnI and in 6 players BNP (5%) exceeded the upper range limit for increased risk of myocardial damage (cTnI ≥ 5 ng/l) and myocardial wall stress (BNP ≥ 100 pg/ml) post-match, respectively. No correlation was observed between Δ cTnI (pre- vs. post-match) and the number of CVRF (r = -0.06, p = 0.50). Follow-up was conducted in 62 players (31 cTnI-positive and 31 cTnI-negative players) of which 6 (10%, 3 cTnI positive and 3 cTnI negative players) had cardiac abnormalities (hypertrophic cardiomyopathy n = 2, coronary artery disease n = 2, coronary artery anomaly n = 1, hypertensive heart disease n = 1). Conclusion: Veterans' football matches elicit increases in BNP and particularly cTnI in a considerable number of players. However, these biochemical alterations do not indicate acute cardiac damage as evidenced by follow-up. Routine determination of cardiac biomarkers is unlikely to improve cardiovascular screening in veteran football players. [ABSTRACT FROM AUTHOR]

Background: Treatment of cardiovascular diseases (CVD) is a substantial burden to healthcare systems worldwide. New tools are needed to improve precision of treatment by optimizing the balance between efficacy, safety, and cost. We developed a high-throughput multi-marker decision support instrument which simultaneously quantifies proteins associated with CVD. Methods and findings: Candidate proteins independently associated with different clinical outcomes were selected from clinical studies by the screening of 368 circulating biomarkers. We then custom-designed a quantitative PEA-panel with 21 proteins (CVD-21) by including recombinant antigens as calibrator samples for normalization and absolute quantification of the proteins. The utility of the CVD-21 tool was evaluated in plasma samples from a case-control cohort of 4224 patients with chronic coronary syndrome (CCS) using multivariable Cox regression analyses and machine learning techniques. The assays in the CVD-21 tool gave good precision and high sensitivity with lower level of determination (LOD) between 0.03–0.7 pg/ml for five of the biomarkers. The dynamic range for the assays was sufficient to accurately quantify the biomarkers in the validation study except for troponin I, which in the modeling was replaced by high-sensitive cardiac troponin T (hs-TnT). We created seven different multimarker models, including a reference model with NT-proBNP, hs-TnT, GDF-15, IL-6, and cystatin C and one model with only clinical variables, for the comparison of the discriminative value of the CVD-21 tool. All models with biomarkers including hs-TnT provided similar discrimination for all outcomes, e.g. c-index between 0.68–0.86 and outperformed models using only clinical variables. Most important prognostic biomarkers were MMP-12, U-PAR, REN, VEGF-D, FGF-23, TFF3, ADM, and SCF. Conclusions: The CVD-21 tool is the very first instrument which with PEA simultaneously quantifies 21 proteins with associations to different CVD. Novel pathophysiologic and prognostic information beyond that of established biomarkers were identified by a number of proteins. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 infection had spread worldwide causing many deaths. Mortality rates and patients' characteristics varied within and between countries, making it important to understand the peculiarities of different populations. The aim of this study was to identify the main predictors associated with in-hospital mortality due to COVID-19 in Vilnius, Lithuania. Materials and methods: This was a retrospective observational cohort study conducted at Vilnius University Hospital Santaros Clinics, Lithuania. The study included SARS-CoV-2 positive patients aged over 18 years and hospitalized between March 2020 and May 2021. Depersonalized data were retrieved from electronic medical records. The predictive values of laboratory parameters were evaluated using ROC analysis. Multivariable binary logistic regression was performed to reveal predictors of in-hospital mortality due to COVID-19. Results: Among 2794 patients, 54.4% were male, the age median was 59 years (IQR 48–70), 47.4% had at least one comorbidity. The most common comorbidities were arterial hypertension (36.9%) and diabetes mellitus (13.7%). Overall, 12.7% of patients died. Multivariable regression revealed that age (OR 1.04, 95%CI 1.02–1.06), congestive heart failure (OR 3.06, 95%CI 1.96–4.77), obesity (OR 3.90, 95%CI 2.12–7.16), COPD (OR 2.92, 95%CI 1.12–7.60), previous stroke (OR 5.80, 95%CI 2.07–16.21), urea >7.01 mmol/l (OR 2.32, 95%CI 1.47–3.67), AST/ALT >1.49 (OR 1.54, 95%CI 1.08–2.21), LDH >452.5 U/l (OR 2.60, 95%CI 1.74–3.88), CRP >92.68 mg/l (OR 1.58, 95%CI 1.06–2.35), IL-6 >69.55 ng/l (OR 1.62, 95%CI 1.10–2.40), and troponin I >18.95 ng/l (OR 2.04, 95%CI 1.38–3.02), were associated with increased risk for in-hospital mortality in COVID-19 patients. Conclusions: Age, congestive heart failure, obesity, COPD, prior stroke, and increased concentration of urea, LDH, CRP, IL-6, troponin I, ALT to AST ratio were identified to be the predictors for in-hospital mortality of COVID-19 patients. [ABSTRACT FROM AUTHOR]

Cardiac troponin I (cTnI) is considered the gold standard biomarker for myocardial injury and shows a high degree of homology between humans and dogs. The ADVIA Centaur XP High-Sensitivity Troponin I (AC-cTnI-HS) assay has been validated for use in humans but not dogs. The study objectives were to analytically validate the AC-cTnI-HS assay in dogs, to assess correlation between the AC-cTnI-HS and a previous ADVIA Centaur TnI-Ultra (AC-cTnI-U) assay, to assess cTnI sample storage stability, and to clinically evaluate the AC-cTnI-HS assay in healthy dogs and dogs with cardiac disease. Canine serum samples were used for analytical validation. Intra- and inter-assay variability, dilutional parallelism, and spiking recovery were assessed. Samples from 196 client-owned dogs were evaluated (healthy dogs (n = 39) or dogs with congenital heart disease (n = 54), myxomatous mitral valve disease (n = 68), dilated cardiomyopathy (n = 15), or myocarditis (n = 20)). Inter- and intra-assay coefficient of variation (%CV) was between 2.8–41.4% and 3.8–30.2%, respectively, with pools with concentrations >20 pg/mL all having %CVs <10%. The observed to expected ratios for dilutional parallelism and spiking recovery experiments ranged between 92.3 and 266.7.0% and 84.3 and 108%, respectively. A strong correlation between the AC-cTnI-HS and AC-cTnI-U assays was observed (Spearman's ρ = 0.927), though a proportional bias existed, with AC-cTnI-HS assay concentrations being proportionally lower than AC-cTnI-U assay concentrations. Serum samples stored at -80°C had stable cTnI measurements for up to 2.7 years and after a single freeze-thaw cycle. Healthy dogs and dogs with congenital heart disease had significantly lower cTnI concentrations than dogs in the other three groups. The AC-cTnI-HS assay precisely, reproducibly, and accurately measures cTnI concentrations in dog serum with cTnI concentrations >20 pg/mL. [ABSTRACT FROM AUTHOR]

Introduction: The wearable cardioverter defibrillator (WCD) is used to protect patients at risk for sudden cardiac arrest. We examined defibrillation efficacy and safety of a biphasic truncated exponential waveform designed for use in a contemporary WCD in three animal studies and a human study. Methods: Animal (swine) studies: #1: Efficacy comparison of a 170J BTE waveform (SHOCK A) to a 150J BTE waveform (SHOCK B) that approximates another commercially available waveform. Primary endpoint first shock success rate. #2: Efficacy comparison of the two waveforms at attenuated charge voltages in swine at three prespecified impedances. Primary endpoint first shock success rate. #3: Safety comparison of SHOCK A and SHOCK B in swine. Primary endpoint cardiac biomarker level changes baseline to 6 and 24 hours post-shock. Human Study: Efficacy comparison of SHOCK A to prespecified goal and safety evaluation. Primary endpoint cumulative first and second shock success rate. Safety endpoint adverse events. Results: Animal Studies #1: 120 VF episodes in six swine. First shock success rates for SHOCK A and SHOCK B were 100%; SHOCK A non-inferior to SHOCK B (entire 95% CI of rate difference above -10% margin, p <.001). #2: 2,160 VF episodes in thirty-six swine. Attenuated SHOCK A was non-inferior to attenuated SHOCK B at each impedance (entire 95% CI of rate difference above -10% margin, p <.001). #3: Ten swine, five shocked five times each with SHOCK A, five shocked five times each with SHOCK B. No significant difference in troponin I (p = 0.658) or creatine phosphokinase (p = 0.855) changes from baseline between SHOCK A and SHOCK B. Human Study: Thirteen patients, 100% VF conversion rate. Mild skin irritation from adhesive defibrillation pads in three patients. Conclusions: The BTE waveform effectively and safely terminated induced VF in swine and a small sample in humans. Trial registration: Human study clinical trial registration: URL: https://clinicaltrials.gov; Unique identifier: NCT04132466. [ABSTRACT FROM AUTHOR]

While the adult human heart is primarily composed of cardiomyocytes, fibroblasts, endothelial and smooth muscle cells, the cellular composition during early development remains largely unknown. Reliable identification of fetal cardiac cell types using protein markers is critical to understand cardiac development and delineate the cellular composition of the developing human heart. This is the first study to use immunohistochemistry (IHC), flow cytometry and RT-PCR analyses to investigate the expression and specificity of commonly used cardiac cell markers in the early human fetal heart (8–12 post-conception weeks). The expression of previously reported protein markers for the detection of cardiomyocytes (Myosin Heavy Chain (MHC) and cardiac troponin I (cTnI), fibroblasts (DDR2, THY1, Vimentin), endothelial cells (CD31) and smooth muscle cells (α-SMA) were assessed. Two distinct populations of cTnI positive cells were identified through flow cytometry, with MHC positive cardiomyocytes showing high cTnI expression (cTnIHigh) while MHC negative non-myocytes showed lower cTnI expression (cTnILow). cTnI expression in non-myocytes was further confirmed by IHC and RT-PCR analyses, suggesting troponins are not cardiomyocyte-specific and may play distinct roles in non-muscle cells during early development. Vimentin (VIM) was expressed in cultured ventricular fibroblast populations and flow cytometry revealed VIMHigh and VIMLow cell populations in the fetal heart. MHC positive cardiomyocytes were VIMLow whilst CD31 positive endothelial cells were VIMHigh. Using markers investigated within this study, we characterised fetal human cardiac populations and estimate that 75–80% of fetal cardiac cells are cardiomyocytes and are MHC+/cTnIHigh/VIMLow, whilst non-myocytes comprise 20–25% of total cells and are MHC-/cTnILow/VIMHigh, with CD31+ endothelial cells comprising ~9% of this population. These findings show distinct differences from those reported for adult heart. [ABSTRACT FROM AUTHOR]

An increasing number of patients with cancer are being treated with immune checkpoint inhibitors. Consequently, the incidence of immune checkpoint inhibitor-related myocarditis has been increasing. Nonetheless, the diagnostic criteria for the immune checkpoint inhibitor-related myocarditis have not been sufficiently established. Therefore, the real-world incidence or prevalence of immune checkpoint inhibitor-related myocardial damage remains unknown. This was a single-center cohort study that included 100 patients admitted for immune checkpoint inhibitor therapy for any type of cancer. The patients underwent monthly measurement of cardiac troponin I and N-terminal pro-brain natriuretic peptide levels with electrocardiography. Additionally, echocardiography was performed every 3 months. Our protocol was continued until 6 months after the initiation of immune checkpoint inhibitors. We defined immune checkpoint inhibitor-related myocardial damage as an increase in cardiac troponin I levels by >0.026 ng/mL and/or a decrease in the left ventricular ejection fraction by >10% to <53% on echocardiography. The mean patient age was 64 years; 71% were men. The most commonly used immune checkpoint inhibitor was nivolumab (47%), followed by pembrolizumab (29%). Overall, 5% of patients received combination therapy. Among 100 patients, 10 (10%) were diagnosed with immune checkpoint inhibitor-related myocardial damage. Among them, five patients underwent endomyocardial biopsy. Of these patients, four were histopathologically observed to have lymphocyte infiltration in their myocardium. In conclusion, serial cardiac troponin I measurement during immune checkpoint inhibitor treatment could help detect early-phase myocardial damage. The prevalence of myocardial damage was much higher than previously expected. [ABSTRACT FROM AUTHOR]

Background: Elevations of high-sensitivity cardiac troponin (hs-cTn) concentrations not related to type 1 myocardial infarction are common in chest pain patients presenting to emergency departments. The discrimination of these patients from those with type 1 myocardial infarction (MI) is challenging and resource-consuming. We aimed to investigate whether the hs-cTn I/T ratio might provide diagnostic and prognostic increment in this context. Methods: We calculated the hs-cTn I/T ratio in 888 chest pain patients having hs-cTnI (Abbott Laboratories) or hs-cTnT (Roche Diagnostics) concentrations above the respective 99th percentile at 2 hours from presentation. All patients were followed for one year regarding mortality. Results: The median hs-cTn I/T ratio was 3.45 (25th, 75th percentiles 1.80–6.59) in type 1 MI patients (n = 408 ☯46.0%]), 1.18 (0.81–1.90) in type 2 MI patients (n = 56 ☯6.3%]) and 0.67 (0.39–1.12) in patients without MI. The hs-cTn I/T ratio provided good discrimination of type 1 MI from no type 1 MI (area under the receiver-operator characteristic curve 0.89 ☯95% confidence interval 0.86–0.91]), of type 1 MI from type 2 MI (area under the curve 0.81 ☯95% confidence interval 0.74–0.87]), and was associated with type 1 MI in adjusted analyses. The hs-cTn I/T ratio provided no consistent prognostic value. Conclusions: The hs-cTn I/T ratio appears to be useful for early diagnosis of type 1 MI and its discrimination from type 2 MI in chest pain patients presenting with elevated hs-cTn. Differences in hs-cTn I/T ratio values may reflect variations in hs-cTn release mechanisms in response to different types of myocardial injury. [ABSTRACT FROM AUTHOR]

Background: Echocardiographic measures are known predictors of cardiovascular disease (CVD) in the general population. This study compared the predictive value of such measures to that of circulating cardiac biomarkers for a composite cardiovascular disease outcome in an aging population. Methods: In this prospective population-based cohort study, echocardiography was performed at baseline together with assessments of traditional CVD risk factors and circulating cardiac biomarkers, NT-proBNP and troponin I, in 1016 individuals all aged 70 years. Assessments were repeated at ages 75 and 80. A composite CVD outcome (myocardial infarction, heart failure or ischemic stroke) was charted over 15 years. All echocardiography variables, except for the E/A ratio, were analyzed on a continuous scale. Results: Over 10 years, left atrial (LA) diameter, left ventricular mass index (LVMI) and high E/A ratio (>1.5) increased, while left ventricular ejection fraction (LVEF) remained unchanged. Using Cox proportional hazard analyses with time-updated variables for echocardiographic measures and traditional risk factors, an enlarged LA diameter and a low LVEF were independently related to incident CVD in 222 participants. The addition of LA diameter and LVEF to traditional risk factors increased the C-statistic by 1.5% (p = 0.008). However, the addition of troponin I and NT-proBNP to traditional risk factors increased the C-statistic by 3.0% (p<0.001). Conclusion: An enlarged LA diameter and a low LVEF improved the prediction of incident CVD compared to traditional risk factors. However, given that troponin I and NT-proBNP improved prediction to a similar extent, the use of simple blood tests to improve clinical cardiovascular disease risk prediction is only further supported by this study. [ABSTRACT FROM AUTHOR]

Background: We recently reported that multilineage-differentiating stress enduring (Muse) cells intravenously administered after acute myocardial infarction (AMI), selectively engrafted to the infarct area, spontaneously differentiated into cardiomyocytes and vessels, reduced the infarct size, improved the left ventricular (LV) function and remodeling in rabbits. We aimed to clarify the efficiency of Muse cells in a larger animal AMI model of mini-pigs using a semi-clinical grade human Muse cell product. Method and result: Mini-pigs underwent 30 min of coronary artery occlusion followed by 2 weeks of reperfusion. Semi-clinical grade human Muse cell product (1x107, Muse group, n = 5) or saline (Vehicle group, n = 7) were intravenously administered at 24 h after reperfusion. The infarct size, LV function and remodeling were evaluated by echocardiography. Arrhythmias were evaluated by an implantable loop recorder. The infarct size was significantly smaller in the Muse group (10.5±3.3%) than in the Vehicle group (21.0±2.0%). Both the LV ejection fraction and fractional shortening were significantly greater in the Muse group than in the Vehicle group. The LV end-systolic and end-diastolic dimensions were significantly smaller in the Muse group than in the Vehicle group. Human Muse cells homed into the infarct border area and expressed cardiac troponin I and vascular endothelial CD31. No arrhythmias and no blood test abnormality were observed. Conclusion: Muse cell product might be promising for AMI therapy based on the efficiency and safety in a mini-pig AMI. [ABSTRACT FROM AUTHOR]

Background: The identification of high-risk heart failure (HF) patients makes it possible to intensify their treatment. Our aim was to determine the prognostic value of a newly developed, high-sensitivity troponin I assay (Atellica®, Siemens Healthcare Diagnostics) for patients with HF with reduced ejection fraction (HFrEF; LVEF < 40%) and HF with mid-range EF (HFmrEF) (LVEF 40%–49%). Methods and results: A total of 520 patients with HFrEF and HFmrEF were enrolled in this study. Two-year all-cause mortality, heart transplantation, and/or left ventricular assist device implantation were defined as the primary endpoints (EP). A logistic regression analysis was used for the identification of predictors and development of multivariable models. The EP occurred in 14% of the patients, and these patients had higher NT-proBNP (1,950 vs. 518 ng/l; p < 0.001) and hs-cTnI (34 vs. 17 ng/l, p < 0.001) levels. C-statistics demonstrated that the optimal cut-off value for the hs-cTnI level was 17 ng/l (AUC 0.658, p < 0.001). Described by the AUC, the discriminatory power of the multivariable model (NYHA > II, NT-proBNP, hs-cTnI and urea) was 0.823 (p < 0.001). Including heart failure hospitalization as the component of the combined secondary endpoint leads to a diminished predictive power of increased hs-cTnI. Conclusion: hs-cTnI levels ≥ 17 ng/l represent an independent increased risk of an adverse prognosis for patients with HFrEF and HFmrEF. Determining a patient's hs-cTnI level adds prognostic value to NT-proBNP and clinical parameters. [ABSTRACT FROM AUTHOR]

Background: COVID-19 has been reported in over 40million people globally with variable clinical outcomes. In this systematic review and meta-analysis, we assessed demographic, laboratory and clinical indicators as predictors for severe courses of COVID-19. Methods: This systematic review was registered at PROSPERO under CRD42020177154. We systematically searched multiple databases (PubMed, Web of Science Core Collection, MedRvix and bioRvix) for publications from December 2019 to May 31st 2020. Random-effects meta-analyses were used to calculate pooled odds ratios and differences of medians between (1) patients admitted to ICU versus non-ICU patients and (2) patients who died versus those who survived. We adapted an existing Cochrane risk-of-bias assessment tool for outcome studies. Results: Of 6,702 unique citations, we included 88 articles with 69,762 patients. There was concern for bias across all articles included. Age was strongly associated with mortality with a difference of medians (DoM) of 13.15 years (95% confidence interval (CI) 11.37 to 14.94) between those who died and those who survived. We found a clinically relevant difference between non-survivors and survivors for C-reactive protein (CRP; DoM 69.10 mg/L, CI 50.43 to 87.77), lactate dehydrogenase (LDH; DoM 189.49 U/L, CI 155.00 to 223.98), cardiac troponin I (cTnI; DoM 21.88 pg/mL, CI 9.78 to 33.99) and D-Dimer (DoM 1.29mg/L, CI 0.9 to 1.69). Furthermore, cerebrovascular disease was the co-morbidity most strongly associated with mortality (Odds Ratio 3.45, CI 2.42 to 4.91) and ICU admission (Odds Ratio 5.88, CI 2.35 to 14.73). Discussion: This comprehensive meta-analysis found age, cerebrovascular disease, CRP, LDH and cTnI to be the most important risk-factors that predict severe COVID-19 outcomes and will inform clinical scores to support early decision-making. [ABSTRACT FROM AUTHOR]

Background: The risk of myocardial infarction (MI) increases during pregnancy, particularly in women with pre-eclampsia. MI is diagnosed by measuring high blood levels of cardiac-specific troponin (cTn), although this may be elevated in women with pre-eclampsia without MI, which increases diagnostic uncertainty. It is unclear how much cTn is elevated in uncomplicated and complicated pregnancy, which may affect whether the existing reference intervals can be used in pregnant women. Previous reviews have not investigated high-sensitivity troponin in pregnancy, compared to older, less sensitive methods. Methods: Electronic searches using the terms "troponin I" or "troponin T", and "pregnancy", "pregnancy complications" or "obstetrics". cTn levels were extracted from studies of women with uncomplicated pregnancies or pre-eclampsia. Results: The search identified ten studies with 1581 women. Eight studies used contemporary methods that may be too insensitive to use reliably in this clinical setting. Two studies used high-sensitivity assays, with one reporting an elevation in troponin I (TnI) in pre-eclampsia compared to uncomplicated pregnancy, and the other only examining women with pre-eclampsia. Seven studies compared cTn between women with pre-eclampsia or uncomplicated pregnancy using any assay. Seven studies showed elevated TnI in pre-eclampsia compared to uncomplicated pregnancy or non-pregnant women. One study measured troponin T (TnT) in pregnancy but did not examine pre-eclampsia. Conclusion: TnI appears to be elevated in pre-eclampsia, irrespective of methodology, which may reflect the role of cardiac stress in this condition. TnI may be similar in healthy pregnant and non-pregnant women, but we found no literature reporting pregnancy-specific reference intervals using high-sensitivity tests. This limits broader application of cTn in pregnancy. There is a need to define reference intervals for cTn in pregnant women, which should involve serial sampling throughout pregnancy, with careful consideration for gestational age and body mass index, which cause dynamic changes in normal maternal physiology. [ABSTRACT FROM AUTHOR]

Background: The rapid spread of coronavirus disease 2019 (COVID-19) revealed significant constraints in critical care capacity. In anticipation of subsequent waves, reliable prediction of disease severity is essential for critical care capacity management and may enable earlier targeted interventions to improve patient outcomes. The purpose of this study is to develop and externally validate a prognostic model/clinical tool for predicting COVID-19 critical disease at presentation to medical care. Methods: This is a retrospective study of a prognostic model for the prediction of COVID-19 critical disease where critical disease was defined as ICU admission, ventilation, and/or death. The derivation cohort was used to develop a multivariable logistic regression model. Covariates included patient comorbidities, presenting vital signs, and laboratory values. Model performance was assessed on the validation cohort by concordance statistics. The model was developed with consecutive patients with COVID-19 who presented to University of California Irvine Medical Center in Orange County, California. External validation was performed with a random sample of patients with COVID-19 at Emory Healthcare in Atlanta, Georgia. Results: Of a total 3208 patients tested in the derivation cohort, 9% (299/3028) were positive for COVID-19. Clinical data including past medical history and presenting laboratory values were available for 29% (87/299) of patients (median age, 48 years [range, 21–88 years]; 64% [36/55] male). The most common comorbidities included obesity (37%, 31/87), hypertension (37%, 32/87), and diabetes (24%, 24/87). Critical disease was present in 24% (21/87). After backward stepwise selection, the following factors were associated with greatest increased risk of critical disease: number of comorbidities, body mass index, respiratory rate, white blood cell count, % lymphocytes, serum creatinine, lactate dehydrogenase, high sensitivity troponin I, ferritin, procalcitonin, and C-reactive protein. Of a total of 40 patients in the validation cohort (median age, 60 years [range, 27–88 years]; 55% [22/40] male), critical disease was present in 65% (26/40). Model discrimination in the validation cohort was high (concordance statistic: 0.94, 95% confidence interval 0.87–1.01). A web-based tool was developed to enable clinicians to input patient data and view likelihood of critical disease. Conclusions and relevance: We present a model which accurately predicted COVID-19 critical disease risk using comorbidities and presenting vital signs and laboratory values, on derivation and validation cohorts from two different institutions. If further validated on additional cohorts of patients, this model/clinical tool may provide useful prognostication of critical care needs. [ABSTRACT FROM AUTHOR]

Background: To date, several clinical laboratory parameters associated with Coronavirus disease 2019 (COVID-19) severity have been reported. However, these parameters have not been observed consistently across studies. The aim of this review was to assess clinical laboratory parameters which may serve as markers or predictors of severe or critical COVID-19. Methods and findings: We conducted a systematic search of MEDLINE, Embase, Web of Science, CINAHL and Google Scholar databases from 2019 through April 18, 2020, and reviewed bibliographies of eligible studies, relevant systematic reviews, and the medRxiv pre-print server. We included hospital-based observational studies reporting clinical laboratory parameters of confirmed cases of COVID-19 and excluded studies having large proportions (>10%) of children and pregnant women. Two authors independently carried out screening of articles, data extraction and quality assessment. Meta-analyses were done using random effects model. Meta-median difference (MMD) and 95% confidence interval (CI) was calculated for each laboratory parameter. Forty-five studies in 6 countries were included. Compared to non-severe COVID-19 cases, severe or critical COVID-19 was characterised by higher neutrophil count (MMD: 1.23 [95% CI: 0.58 to 1.88] ×109 cells/L), and lower lymphocyte, CD4 and CD8 T cell counts with MMD (95% CI) of -0.39 (-0.47, -0.31) ×109 cells/L, -204.9 (-302.6, -107.1) cells/μl and -123.6 (-170.6, -76.6) cells/μl, respectively. Other notable results were observed for C-reactive protein (MMD: 36.97 [95% CI: 27.58, 46.35] mg/L), interleukin-6 (MMD: 17.37 [95% CI: 4.74, 30.00] pg/ml), Troponin I (MMD: 0.01 [0.00, 0.02] ng/ml), and D-dimer (MMD: 0.65 [0.45, 0.85] mg/ml). Conclusions: Relative to non-severe COVID-19, severe or critical COVID-19 is characterised by increased markers of innate immune response, decreased markers of adaptive immune response, and increased markers of tissue damage and major organ failure. These markers could be used to recognise severe or critical disease and to monitor clinical course of COVID-19. [ABSTRACT FROM AUTHOR]

A multi-site, steady-state Förster resonance energy transfer (FRET) approach was used to quantify Ca(2+)-induced changes in proximity between donor loci on human cardiac troponin I (cTnI), and acceptor loci on human cardiac tropomyosin (cTm) and F-actin within functional thin filaments. A fluorescent donor probe was introduced to unique and key cysteine residues on the C- and N-termini of cTnI. A FRET acceptor probe was introduced to one of three sites located on the inner or outer domain of F-actin, namely Cys-374 and the phalloidin-binding site on F-actin, and Cys-190 of cTm. Unlike earlier FRET analyses of protein dynamics within the thin filament, this study considered the effects of non-random distribution of dipoles for the donor and acceptor probes. The major conclusion drawn from this study is that Ca(2+) and myosin S1-binding to the thin filament results in movement of the C-terminal domain of cTnI from the outer domain of F-actin towards the inner domain, which is associated with the myosin-binding. A hinge-linkage model is used to best-describe the finding of a Ca(2+)-induced movement of the C-terminus of cTnI with a stationary N-terminus. This dynamic model of the activation of the thin filament is discussed in the context of other structural and biochemical studies on normal and mutant cTnI found in hypertrophic cardiomyopathies.

Recent discoveries of at least two heart fields and dynamic nature of cardiac development as well as controversies regarding the participation of heart fields in development of different heart structures led us to investigate the dynamics of incorporation of the first and second heart fields and prospective fate of the straight heart tube by labeling chicken embryos in vivo with the fluorescent lipophilic dye DiI. The cephalic and caudal limits of the anterior and posterior segments of the straight heart tube were labeled in two groups of embryos. Labels were tracked along the "C," "S," and "U" loops up to the tetracavitary or mature heart (n = 30 embryos/group; torsion and looping stage). To determine whether the atria and atrioventricular canal are derived from the first heart field the straight heart tube was cultured in vitro and immunodetection of Sox-9 and troponin I was performed to identify the mesenchymal and myocardial lineages respectively. Proliferating cell nuclear antigen (PCNA) immunodetection was used to determine the involvement of cell proliferation in heart tube development during torsion and looping. Embryological constitution of the straight heart tube and heart looping (C, S, and U) were not consistent with current descriptions. In fact, right ventricle precursors were absent in the straight heart tube derived from the first heart field. During torsion and looping, the cephalic segment of the straight heart tube gradually shifted into the heart tube until it was located at the myocardial interventricular septum in the tetracavitary heart. In contrast, the caudal segment of the straight heart tube was elongated and remodeled to become the first heart field derived left ventricle and the proximal part of the ventricular inlets. The ventricular outflows, right ventricle, distal part of the ventricular inlets, and atria developed from the second heart field. [ABSTRACT FROM AUTHOR]

Background: Approximately 30,000 patients with blunt cardiac trauma are recorded each year in the United States. Blunt cardiac injuries after trauma are associated with a longer hospital stay and a poor overall outcome. Organ damage after trauma is linked to increased systemic release of pro-inflammatory cytokines and damage-associated molecular patterns. However, the interplay between polytrauma and local cardiac injury is unclear. Additionally, the impact of surgical intervention on this process is currently unknown. This study aimed to determine local cardiac immunological and structural alterations after multiple trauma. Furthermore, the impact of the chosen fracture stabilization strategy (reamed versus non-reamed femoral nailing) on cardiac alterations was studied. Experimental approach: 15 male pigs were either exposed to multiple trauma (blunt chest trauma, laparotomy, liver laceration, femur fracture and haemorrhagic shock) or sham conditions. Blood samples as well as cardiac tissue were analysed 4 h and 6 h after trauma. Additionally, murine HL-1 cells were exposed to a defined polytrauma-cocktail, mimicking the pro-inflammatory conditions after multiple trauma in vitro. Results: After multiple trauma, cardiac structural changes were observed in the left ventricle. More specifically, alterations in the alpha-actinin and desmin protein expression were found. Cardiac structural alterations were accompanied by enhanced local nitrosative stress, increased local inflammation and elevated systemic levels of the high-mobility group box 1 protein. Furthermore, cardiac alterations were observed predominantly in pigs that were treated by non-reamed intramedullary reaming. The polytrauma-cocktail impaired the viability of HL-1 cells in vitro, which was accompanied by a release of troponin I and HFABP. Discussion: Multiple trauma induced cardiac structural alterations in vivo, which might contribute to the development of early myocardial damage (EMD). This study also revealed that reamed femoral nailing (reamed) is associated with more prominent immunological cardiac alterations compared to nailing without reaming (non-reamed). This suggests that the choice of the initial fracture treatment strategy might be crucial for the overall outcome as well as for any post-traumatic cardiac consequences. [ABSTRACT FROM AUTHOR]

The outbreak of Coronavirus Disease (COVID-19) in Wuhan have affected more than 250 countries and regions worldwide. However, most of the clinical studies have been focused on Wuhan, and little is known about the disease outside of Wuhan in China. In this retrospective cohort study, we report the early clinical features of 80 patients with COVID-19 admitted to the hospital in Beijing. The results show that 27 (33.8%) patients had severe illness. Six (7.5%) patients were admitted to the ICU, and 3 (3.8%) patients died. Forty-eight percent (39/80) of the patients had a history of living/traveling in Wuhan. Patients with severe- illness were significantly older (average age, 71 years old vs 44 years old) and had a high incidence of expectoration (59.3% vs 34.0%), shortness of breath (92.6% vs 9.4%), anorexia (51.9% vs 18.9%) and confusion(18.5% vs 0%) compared with nonsevere patients. The systolic blood pressure (median, 130 mmHg vs 120 mmHg) was higher and the oxygen saturation (median, 98.3% vs 92.0%) was significantly lower in severe patients than nonsevere patients. In addition, myoglobin (median, 56.0 ng/mL vs 35.0 ng/mL), troponin I (median, 0.02 pg/mL vs 0.01 pg/mL), C-reactive protein (median, 69.7 mg/L vs 12.9 mg/L) and neutrophils (median, 3.3×109/L vs 2.2×109/L) were significantly increased, while lymphocytes (median, 0.8×109/L vs 1.2×109/L), albumin (mean, 32.8 g/L vs 36.8 g/L) and the creatinine clearance rate (median, 91.2 vs 108.2 ml/min/1.73m2) were significantly decreased among severe patients. Our study revealed that older patients with high levels of C-reactive protein, myoglobin, troponin I, and neutrophil and high systolic blood pressure as well as low levels of lymphocytes, and albumin and a low creatinine clearance rate and oxygen saturation were more likely to have severe disease. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate efficacy of antithrombotic agents in critically ill patients with elevated troponin I level during intensive care unit (ICU) admission. Methods and results: It was a retrospective observational study which was conducted in a tertiary teaching hospital in Taipei, Taiwan. All patients hospitalized in ICU for >3 days and with available serum troponin I data from December 2015 to July 2017 were included. Patients with definite diagnosis of acute myocardial infarction (AMI) were excluded. We divided patients with troponin I elevation into three groups; no prescription, chronic prescription and new prescription of antithrombotic agents during ICU admission. We defined new prescription when patients were on antithrombotic agents, including antiplatelet agents, direct oral anticoagulants, and warfarin after troponin I was found to be elevated at ICU admission and chronic prescription, if antithrombotic agents were on medication list more than 30 days before ICU admission. Primary outcomes were 30-day and one-year all-cause mortality. Of 597 subjects who met inclusion criteria, 407 (68%) patients had elevated troponin I (>0.1 ng/mL) on ICU admission. These patients had increased 30-day [hazard ratio (HR), 1.679; 95% confidence interval (CI), 1.132–2.491; p = 0.009] and one-year (HR, 1.568; 95% CI, 1.180–2.083; p = 0.002) all-cause mortality compared with those without elevated troponin I. In patients with elevated troponin I, there was no significant difference of 30-day all-cause mortality among three groups (p = 0.051) whereas patients on chronic prescription showed significant survival benefit in one-year all-cause mortality when compared to those without or with new prescription (p = 0.008). Conclusions: In critically ill patients, elevated troponin I in the absence of AMI was associated with poor prognosis. Newly prescribed antithrombotic agents in ICU didn't reveal the difference in short and long-term prognosis while chronic antithrombotic agent use was associated with better one-year survival rate, suggesting that these drugs play a protective role in this high-risk population. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) have attracted increasing attention because of their potential roles in various biological processes and medical applications. However, isolation of EVs is technically challenging mainly due to their small and heterogeneous size and contaminants that are often co-isolated. We have thus designed a two-step magnetic bead-based (2MBB) method for isolation a subset of EVs as well as their microRNAs from samples of a limited amount. The process involves utilizing magnetic beads coated with capture molecules that recognize EV surface markers, such as CD63. Captured EVs could be eluted from beads or lyzed directly for subsequent analysis. In this study, we used a second set of magnetic beads coated with complementary oligonucleotides to isolate EV-associated microRNAs (EV-miRNAs). The efficiencies of 2MBB processes were assessed by reverse transcription-polymerase chain reaction (RT-PCR) with spiked-in exogenous cel-miR-238 molecules. Experimental results demonstrated the high efficiency in EV enrichment (74 ± 7%, n = 4) and miRNA extraction (91 ± 4%, n = 4). Transmission electron micrographs (TEM) and nanoparticle tracking analysis (NTA) show that captured EVs enriched by 2MBB method could be released and achieved a higher purity than the differential ultracentrifugation (DUC) method (p < 0.001, n = 3). As a pilot study, EV-miR126-3p and total circulating cell-free miR126-3p (cf-miR126-3p) in eight clinical plasma samples were measured and compared with the level of protein markers. Compared to cf-miR126-3p, a significant increase in correlations between EV-miR126-3p and cardiac troponin I (cTnI) and N-terminal propeptide of B-type natriuretic peptide (NT-proBNP) was detected. Furthermore, EV-miR126-3p levels in plasma samples from healthy volunteers (n = 18) and high-risk cardiovascular disease (CVD) patients (n = 10) were significantly different (p = 0.006), suggesting EV-miR126 may be a potential biomarker for cardiovascular diseases. 2MBB technique is easy, versatile, and provides an efficient means for enriching EVs and EV-associated nucleic acid molecules. [ABSTRACT FROM AUTHOR]

Objectives: Dexmedetomidine (DEX) is a selective α2-adrenoceptor agonist that has anti-inflammatory and cardioprotective effects in myocardial ischemia/reperfusion (I/R) injury. The present study aimed to investigate the underlying mechanism by which DEX protects against myocardial I/R. Methods: Sprague Dawley rats were subjected to either sham operation or myocardial I/R, which was induced by ligating the left anterior descending coronary artery for 30 min followed by reperfusion for 120 min. Rats were treated with either DEX or saline prior to surgery. We measured heart infarct size, serum cardiac Troponin I (cTnI), cardiac High mobility group box-1 (HMGB1) expression, myocardial apoptosis and cytokine production of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Besides, we evaluated the heart function at 4 weeks post-reperfusion by echocardiography. Unilateral vagotomy or inhibition of the α7 nicotinic acetylcholine receptor (α7nAChR) with methyllycaconitine (MLA) was applied to investigate whether DEX-induced cardioprotection is mediated via the cholinergic anti-inflammatory pathway. Cardiac-selective overexpression of HMGB1 was administered to further confirm if HMGB1 is a key anti-inflammatory target during DEX-induced cardioprotection. Results: DEX pretreatment significantly attenuated I/R-induced cardiac damage, as evidenced by decreases in short-term injury indicators including myocardial infarct size, cTnI release, myocardial apoptosis, cardiac HMGB1 expression, IL-6 and TNF-α production, as well as improvement on long-term cardiac function at 4 weeks post-reperfusion. These effects were partially reversed by either unilateral vagotomy or methyllycaconitine treatment. Besides, cardiac HMGB1-overexpression nearly abolished DEX-induced cardioprotection. Conclusions: DEX pretreatment protects against myocardial I/R by inhibiting cardiac HMGB1 production and activating the cholinergic anti-inflammatory pathway. [ABSTRACT FROM AUTHOR]

Background: Whether high-sensitivity cardiac troponin elevation during the perioperative period is associated with poor clinical outcome in revascularized coronary patients who undergo noncardiac surgery remains unclear. We investigated the effects of perioperative troponin elevation on the long-term clinical outcomes of patients with a history of coronary revascularization. Methods: We analyzed patients whose pre- or postoperative high-sensitivity cardiac troponin I (hs-cTnI) assay results were available. Patients were divided into two groups according to hs-cTnI levels. The patient groups were analyzed separately according to whether hs-cTnI was assessed preoperatively or postoperatively. The primary outcome was all-cause death during the follow-up period. Results: Median follow-up duration was 25 months (interquartile range 11–50). In the propensity-matched analysis, the risk of all-cause death during follow-up was higher in the group with elevated hs-cTnI group than in the normal group (12.7% vs 6.3%; hazard ratio [HR], 2.67; 95% confidential interval [CI], 1.04–6.82; p = 0.04). In the propensity-matched analysis of preoperative hs-cTnI levels, we found no significant difference between the groups in the rate of all-cause death (12.9% vs. 11.9%; HR, 1.06; 95% CI, 0.45–2.50; p = 0.89). In the postoperative propensity-matched analysis, all-cause death was higher in patients with elevated hs-cTnI than in those with normal levels (14.9% vs. 5.9%; HR, 2.80; 95% CI, 1.01–7.77; p = 0.048). Conclusion: In revascularized coronary patients who underwent noncardiac surgery, postoperative (but not preoperative) hs-cTnI elevation was associated with all-cause death during follow-up. Larger datasets are needed to support this finding. [ABSTRACT FROM AUTHOR]

Pediatric myocarditis symptoms can be mild or as extreme as sudden cardiac arrest. Early identification of the severity of illness and timely provision of critical care is helpful; however, the risk factors associated with mortality remain unclear and controversial. We undertook a retrospective review of the medical records of pediatric patients with myocarditis in a tertiary care referral hospital for over 12 years to identify the predictive factors of mortality. Demographics, presentation, laboratory test results, echocardiography findings, and treatment outcomes were obtained. Regression analyses revealed the clinical parameters for predicting mortality. During the 12-year period, 94 patients with myocarditis were included. Of these, 16 (17%) patients died, with 12 succumbing in the first 72 hours after admission. Fatal cases more commonly presented with arrhythmia, hypotension, acidosis, gastrointestinal symptoms, decreased left ventricular ejection fraction, and elevated isoenzyme of creatine kinase and troponin I levels than nonfatal cases. In multivariate analysis, troponin I > 45 ng/mL and left ventricular ejection fraction < 42% were significantly associated with mortality. Pediatric myocarditis had a high mortality rate, much of which was concentrated in the first 72 hours after hospitalization. Children with very high troponin levels or reduced ejection fraction in the first 24 hours were at higher risk of mortality, and targeting these individuals for more intensive therapies may be warranted. [ABSTRACT FROM AUTHOR]

Background: We aimed to investigate the values and the changes of brain natriuretic peptide (BNP) and cardiac troponin in pregnant women. Methods and results: We prospectively collected the data of 405 pregnant women who were treated at Japanese general hospital between 2012 and 2013. We analyzed their laboratory data and echocardiographic findings during the third trimester (28–30 weeks’ gestation) and within 4 days of delivery. In addition, we evaluated the factors associated with elevation of BNP and cardiac troponin I (cTnI) levels. The pregnant women were 33.8 ± 5.0 years old and the prevalence of pregnancy induced hypertension (PIH) and placental abnormality was 4.2% and 2.5%, respectively. BNP levels increased after delivery (13.2 pg/mL vs. 23.5 pg/mL; P <0.001), correlated with increased left ventricular diastolic dimension (P = 0.035), left atrial dimension (P <0.001), and decreased hemoglobin (P <0.001). Moreover, cTnI levels increased to over 0.015 ng/mL after delivery in 4.0% of pregnant women. In multivariate analysis, PIH (OR: 18.71, P = 0.003), placental abnormality (OR: 26.78, P = 0.007), and decreased hemoglobin after delivery (OR: 2.59, P <0.001) were the factors associated with elevated cTnI. Conclusions: BNP levels increased in association with cardiac chamber enlargement and decreased hemoglobin after delivery. Additionally, the factors affecting elevated cTnI levels were related to labor and delivery. [ABSTRACT FROM AUTHOR]

Introduction: Despite relevant evidence that supplemental oxygen therapy can be harmful to patients with myocardial injury, the association between hyperoxia and the clinical outcome of such patients has not been evaluated. We assessed whether early hyperoxia negatively affects outcomes in hospitalized patients with myocardial injury. Methods: This was a retrospective study conducted at a tertiary referral teaching hospital. Between January 2010 and December 2016, 2,376 consecutive emergency department patients with myocardial injury, defined as a peak troponin-I level ≥ 0.2 ng/mL, within the first 24 hours of presentation were included. The metrics used to define hyperoxia were the maximum average partial pressure of oxygen (PaO2MAX), average partial pressure of oxygen (PaO2AVG), and area under the curve during the first 24 hours (AUC24). The association between early hyperoxia within 24 hours after presentation and clinical outcomes was evaluated using multiple imputation and logistic regression analysis. The primary outcome was 28-day in-hospital mortality. The secondary outcomes were new-onset cardiovascular, coagulation, hepatic, renal, and respiratory dysfunctions (sequential organ failure sub-score ≥ 2). Results: Compared with normoxic patients, the adjusted odds ratios (ORs) for PaO2MAX, PaO2AVG, and AUC24 were 1.55 (95% confidence interval (CI) 1.05–2.27; p = 0.026), 2.13 (95% CI 1.45–3.12; p = 0.001), and 1.73 (95% CI 1.15–2.61; p = 0.008), respectively, in patients with mild hyperoxia and 6.01 (95% CI 3.98–9.07; p < 0.001), 8.92 (95% CI 3.33–23.88; p < 0.001), and 7.32 (95% CI 2.72–19.70; p = 0.001), respectively, in patients with severe hyperoxia. The incidence of coagulation and hepatic dysfunction (sequential organ failure sub-score ≥ 2) was significantly higher in the mild and severe hyperoxia group. Conclusions: Hyperoxia during the first 24 hours of presentation is associated with an increased 28-day in-hospital mortality rate and risks of coagulation and hepatic dysfunction in patients with myocardial injury. [ABSTRACT FROM AUTHOR]

Exercise intolerance is the first symptom of heart disease. Yet an objective and standardised method in canine cardiology to assess exercise capacity in a clinical setting is lacking. In contrast, exercise testing is a powerful diagnostic tool in humans, providing valuable information on prognosis and impact of therapeutic intervention. To investigate whether an exercise test reveals differences between dogs with early stage mitral regurgitation (MR) and dogs without cardiac disease, 12 healthy beagles (healthy group, HG) and 12 dogs with presymptomatic MR (CHIEF B1 / B2, patient group, PG) underwent a six-stage submaximal exercise test (ET) on a motorised treadmill. They trotted in their individual comfort speed for three minutes per stage, first without incline, afterwards increasing it by 4% for every subsequent stage. Blood samples were taken at rest and during two 3-minute breaks in the course of the test. Further samples were taken after the completion of the exercise test and again after a 3-hour recovery period. Measured parameters included heart rate, lactate and the cardiac biomarkers N-terminal pro-B-Type natriuretic peptide and cardiac Troponin I. The test was performed again under the same conditions in the same dogs three weeks after the first trial to evaluate individual repeatability. Cardiac biomarkers increased significantly in both HG and PG in the course of the test. The increase was more pronounced in CHIEF B1 / B2 dogs than in the HG. N-terminal pro-B-Type natriuretic peptide increased from 435 ± 195 to 523 ± 239 pmol/L (HG) and from 690 to 815 pmol/L (PG). cTnI increased from 0.020 to 0.024 ng/mL (HG) and from 0.06 to 0.08 ng/ml (PG). The present study provides a method to assess exercise-induced changes in cardiac biomarkers under clinical conditions. The increase of NT-proBNP and cTnI is more pronounced in dogs with early-stage MR than in healthy dogs. Results indicate that measuring the parameters before and after exercise is adequate and taking blood samples between the different stages of the ET does not provide additional information. Also, stress echocardiography was inconclusive. It can be concluded that exercise testing, especially in combination with measuring cardiac biomarkers, could be a helpful diagnostic tool in canine cardiology. [ABSTRACT FROM AUTHOR]

Objective: There is a clinical need for early and accurate diagnosis of acute myocardial infarction (AMI). Current European Society of Cardiology (ESC) guidelines recommend diagnosis of non-ST-elevation AMI based on serial troponin measurements. We aimed to challenge the ESC guidelines using 1) a high-sensitivity troponin I (hs-TnI) baseline cutoff, 2) an absolute hs-TnI change after 1 hour and 3) additional application of an ischemic ECG. Methods: 1,516 patients with suspected AMI presenting to the emergency department were included. Hs-TnI was measured directly at admission, after 1 and 3 hours. We investigated baseline concentrations, absolute changes of hs-TnI and additional application of an ischemic ECG to diagnose AMI. A positive predictive value (PPV) of more than 85% was targeted. Results: The median age of the study population was 65 years; 291 patients were diagnosed with AMI. The PPV of the 3-hours ESC algorithm was 85.5% (CI 79.7, 90.1) and 65.8% (CI 60.5,70.8) for the 1-hour algorithm. Using a high baseline hs-TnI concentration of 150 ng/L resulted in a PPV of 87.8% (CI 80.9,92.9). Alternatively, a hs-TnI change of 20 ng/L after 1 hour, resulted in a PPV of 86.5% (80.9,91.0), respectively for the diagnosis of AMI. Additional use of an ischemic ECG increased the PPV to 90.5% (CI 83.2,95.3), while reducing the efficacy. Conclusion: The diagnosis of AMI based on hs-TnI is challenging. The application of absolute hs-TnI changes after 1 hour may facilitate rapid rule-in of patients. Trial registration: (). [ABSTRACT FROM AUTHOR]

Objective: High sensitivity plasma cardiac troponin-I (cTnI) is emerging as a strong predictor of cardiac events in a variety of settings. We have explored its utility in patients with myotonic dystrophy type 1 (DM1). Methods: 117 patients with DM1 were recruited from routine outpatient clinics across three health boards. A single measurement of cTnI was made using the ARCHITECT STAT Troponin I assay. Demographic, ECG, echocardiographic and other clinical data were obtained from electronic medical records. Follow up was for a mean of 23 months. Results: Fifty five females and 62 males (mean age 47.7 years) were included. Complete data were available for ECG in 107, echocardiography in 53. Muscle Impairment Rating Scale score was recorded for all patients. A highly significant excess (p = 0.0007) of DM1 patients presented with cTnI levels greater than the 99th centile of the range usually observed in the general population (9 patients; 7.6%). Three patients with elevated troponin were found to have left ventricular systolic dysfunction (LVSD), compared with four of those with normal range cTnI (33.3% versus 3.7%; p = 0.001). Sixty two patients had a cTnI level < 5ng/L, of whom only one had documented evidence of LVSD. Elevated cTnI was not predictive of severe conduction abnormalities on ECG, or presence of a cardiac device, nor did cTnI level correlate with muscle strength expressed by Muscle Impairment Rating Scale score. Conclusions: Plasma cTnI is highly elevated in some ambulatory patients with DM1 and shows promise as a tool to aid cardiac risk stratification, possibly by detecting myocardial involvement. Further studies with larger patient numbers are warranted to assess its utility in this setting. [ABSTRACT FROM AUTHOR]

Objectives: Assessment of the clinical severity of Fabry disease (FD), an X-linked, rare, progressive disorder based on a genetic defect in alpha-galactosidase is challenging, especially regarding cardiac involvement. The aim of the study was to evaluate the diagnostic value of cardiac troponin I (cTnI) in discriminating FD patients with cardiac involvement in a large FD patient cohort. Methods: cTnI levels were measured with a contemporary sensitive assay in plasma samples taken routinely from FD patients. The assay was calibrated to measure cTnI levels ≥0.01 ng/ml. Elevated cTnI values (cut-off ≥0.04 ng/ml) were correlated with clinical data. Results: cTnI was assessed in 62 FD patients (median age: 47 years, males: 36%). Elevated cTnI levels were detected in 23 (37%) patients. Patients with a cTnI elevation were older (median 55 years versus 36 years, p<0.001). Elevated cTnI levels were associated with the presence of a LVH (16/23 versus 1/39; OR 65.81, CI: 6.747–641.859; p<0.001). In almost all patients with a left ventricular hypertrophy (LVH) elevated cTnI levels were detected (16/17, 94%). Absolute cTnI levels in patients with LVH were higher than in those without (median 0.23 ng/ml versus 0.02 ng/ml; p<0.001). A cTnI level <0.04ng/ml had a high negative predictive value regarding the presence of a LVH (38/39, 97%). In a control group of non-FD patients (n = 17) with LVH (due to hypertension) none showed cTnI levels ≥0.01 ng/ml. Conclusions: Elevated cTnI levels are common in FD patients, reflecting cardiac involvement. FD patients might benefit from a continuous cTnI monitoring. [ABSTRACT FROM AUTHOR]

Background: Common ECG criteria such as ST-segment changes are of limited value in patients with suspected acute myocardial infarction (AMI) and bundle branch block or wide QRS complex. A large proportion of these patients do not suffer from an AMI, whereas those with ST-elevation myocardial infarction (STEMI) equivalent AMI benefit from an aggressive treatment. Aim of the present study was to evaluate the diagnostic information of cardiac troponin I (cTnI) in hemodynamically stable patients with wide QRS complex and suspected AMI. Methods: In 417 out of 1818 patients presenting consecutively between 01/2007 and 12/2008 in a prospective multicenter observational study with suspected AMI a prolonged QRS duration was observed. Of these, n = 117 showed significant obstructive coronary artery disease (CAD) used as diagnostic outcome variable. cTnI was determined at admission. Results: Patients with significant CAD had higher cTnI levels compared to individuals without (median 250ng/L vs. 11ng/L; p<0.01). To identify patients needing a coronary intervention, cTnI yielded an area under the receiver operator characteristics curve of 0.849. Optimized cut-offs with respect to a sensitivity driven rule-out and specificity driven rule-in strategy were established (40ng/L/96ng/L). Application of the specificity optimized cut-off value led to a positive predictive value of 71% compared to 59% if using the 99th percentile cut-off. The sensitivity optimized cut-off value was associated with a negative predictive value of 93% compared to 89% provided by application of the 99th percentile threshold. Conclusion: cTnI determined in hemodynamically stable patients with suspected AMI and wide QRS complex using optimized diagnostic thresholds improves rule-in and rule-out with respect to presence of a significant obstructive CAD. [ABSTRACT FROM AUTHOR]

Background: Both high-sensitivity cardiac troponin T and B-type natriuretic peptide are useful in detecting myocardial fibrosis, as determined by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR), in patients with non-obstructive hypertrophic cardiomyopathy. However, their values to predict myocardial fibrosis in hypertrophic obstructive cardiomyopathy (HOCM) remain unclear. We investigated the role of N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) and cardiac troponin I (cTnI) to identify LGE-CMR in patients with HOCM. Methods: Peripheral concentrations of NT-proBNP and cTnI were determined in patients with HOCM (n = 163; age = 47.2 ± 10.8 years; 38.7% females). Contrast-enhanced CMR was performed to identify and quantify myocardial fibrosis. Results: LGE was detected in 120 of 163 patients (73.6%). Patients with LGE had significantly higher levels of NT-proBNP and cTnI than those without LGE (1386.2 [904.6–2340.8] vs. 866.6 [707.2–1875.2] pmol/L, P = 0.003; 0.024 [0.010–0.049] vs. 0.010 [0.005–0.021] ng/ml, P <0.001, respectively). The extent of LGE was positively correlated with log cTnI (r = 0.371, P <0.001) and log NT-proBNP (r = 0.211, P = 0.007). On multivariable analysis, both log cTnI and maximum wall thickness (MWT) were independent predictors of the presence of LGE (OR = 3.193, P = 0.033; OR = 1.410, P < 0.001, respectively), whereas log NT-proBNP was not. According to the ROC curve analysis, combined measurements of MWT ≥21 mm and/or cTnI ≥0.025ng/ml indicated good diagnostic performance for the presence of LGE, with specificity of 95% or sensitivity of 88%. Conclusions: Serum cTnI is an independent predictor useful for identifying myocardial fibrosis, while plasma NT-proBNP is only associated with myocardial fibrosis on univariate analysis. Combined measurements of serum cTnI with MWT further improve its value in detecting myocardial fibrosis in patients with HOCM. [ABSTRACT FROM AUTHOR]

Cysteinyl cathepsin K (CatK) is one of the most potent mammalian collagenases involved in cardiovascular disease. Here, we investigated the clinical predictive value of serum CatK levels in patients with chronic heart failure (CHF). We examined 134 patients with CHF, measuring their serum CatK, troponin I, high-sensitive C-reactive protein, and pre-operative N-terminal pro-brain natriuretic peptide levels. The patients were divided into two groups: the 44 patients who showed a left ventricular (LV) ejection fraction (LVEF) < 40% (the “lowLVEF” group) and the 90 patients showing LVEF values ≥ 40% (the “highLVEF” group). The lowLVEF patients had significantly higher serum CatK levels compared to the highLVEF patients (58.4 ± 12.2 vs. 44.7 ± 16.4, P < 0.001). Overall, a linear regression analysis showed that CatK levels correlated negatively with LVEF (r = −0.4, P < 0.001) and positively with LV end-diastolic dimensions (r = 0.2, P < 0.01), LV end-systolic dimensions (r = 0.3, P < 0.001), and left atrial diameters (r = 0.3, P < 0.01). A multiple logistic regression analysis showed that CatK levels were independent predictors of CHF (odds ratio, 0.90; 95% confidence interval, 0.84–0.95; P < 0.01). These data indicate that elevated levels of CatK are closely associated with the presence of CHF and that the measurement of circulating CatK provides a noninvasive method of documenting and monitoring the extent of cardiac remodeling and dysfunction in patients with CHF. [ABSTRACT FROM AUTHOR]

Cyclophilins are a group of highly conserved cytosolic enzymes that have a peptidylprolyl cis/trans isomerase activity. Cyclophilin A (CyPA) can be secreted in the extracellular space by inflammatory cells and upon cell death. The presence of CyPA in patients with non-ischemic cardiomyopathy is associated with poor clinical prognosis. Here, we investigated the inhibition of extracellular CyPA in a mouse model of troponin I-induced autoimmune myocarditis using the strictly extracellular CyPA-inhibitor MM284. Since A/J mice develop severe inflammation and fibrosis after immunization with murine cardiac troponin I (mcTn I), we used this model to analyze the effects of an extracellular CyPA inhibition. As extracellular CyPA-inhibitor we used the recently described CsA-derivate MM284. In vitro studies confirmed that MM284 inhibits CyPA-induced monocytic migration and adhesion. A/J mice immunized with mcTnI were treated with MM284 or vehicle every second day. After 28 days, we found a considerable reduction of myocardial injury and fibrosis. Further analysis revealed a reduced myocardial presence of T-cells and macrophages compared to control treated animals. Whereas MMP-9 expression was reduced significantly by MM284, we observed no significant reduction of inflammatory cytokines such as IL-6 or TNFα. Extracellular CyPA plays an important role in autoimmune myocarditis for myocardial damage and fibrosis. Our data suggest a new pharmacological approach for the treatment of myocardial inflammation and reduction of cardiac fibrosis by inhibition of extracellular CyPA. [ABSTRACT FROM AUTHOR]

Forty-eight Duroc x Landrace x Large White gilts were used to determine the relationship between proteome changes of longissimus muscle and intramuscular fat (IMF) content in arginine-supplemented pigs. Beginning at 60 kg BW, pigs were fed a corn- and soybean meal-based diet supplemented or not with 1% L-arginine until they reached a BW of 100 kg. Supplementation with 1% L-arginine did not affect the growth performance or carcass traits, while it increased IMF content by 32% (P < 0.01), it also decreased the drip loss at 48 h post-mortem and the b* meat color value at 24 h post-mortem; supplementation with 1% dietary L-arginine did not change the proportion of SFA and MUFA in muscle lipids. The proteome changes in longissimus muscle between the control and supplemented pigs showed that L-arginine significantly influenced the abundance of proteins related to energy metabolism, fiber type and structure. The increase in IMF content was positively correlated with the increased abundance of slow twitch troponin I (TNNI1) protein and negatively correlated with myosin heavy chain IIb (MyHC IIb) protein content. It is suggested that the proteome changes in longissimus muscle contributed to the greater IMF content in L-arginine supplemented pigs. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) are small ribonucleotides regulating gene expression. MicroRNAs are present in the blood in a remarkably stable form and have emerged as potential diagnostic markers in patients with cardiovascular disease. Our study aimed to assess circulating miR-133a levels in MHD patients and the relation of miR-133a to cardiac hypertrophy. Methods: We profiled miRNAs using RNA isolated from the plasma of participants. The results were validated in 64 MHD patients and 18 healthy controls. Results: Levels of plasma miR-133a decreased in MHD patients with LVH compared with those in healthy controls. Plasma miR-133a concentrations were negatively correlated with LVMI and IVS. After single hemodialytic treatment, plasma miR-133a levels remained unchanged. Cardiac Troponin I and T were not associated with LVMI and IVS. Conclusions: Our observations supplied the possibility that circulating miR-133a could be a surrogate biomarker of cardiac hypertrophy in MHD patients. [ABSTRACT FROM AUTHOR]

Background: Fabry disease (FD) is a rare lysosomal storage disorder also affecting the heart. The aims of this study were to determine the frequency of cardiac troponin I (cTNI) elevation, a sensitive parameter reflecting myocardial damage, in a smaller cohort of FD-patients, and to analyze whether persistent cTNI can be a suitable biomarker to assess cardiac dysfunction in FD. Methods: cTNI values were determined at least twice per year in 14 FD-patients (6 males and 8 females) regularly followed-up in our centre. The data were related to other parameters of heart function including cardiac magnetic resonance imaging (cMRI). Results: Three patients (21%) without specific vascular risk factors other than FD had persistent cTNI-elevations (range 0.05–0.71 ng/ml, normal: <0.01). cMRI disclosed late gadolinium enhancement (LGE) in all three individuals with cTNI values ≥0.01, while none of the 11 patients with cTNI <0.01 showed a pathological enhancement (p<0.01). Two subjects with increased cTNI-values underwent coronary angiography, excluding relevant stenoses. A myocardial biopsy performed in one during this procedure demonstrated substantial accumulation of globotriaosylceramide (Gb3) in cardiomyocytes. Conclusion: Continuous cTNI elevation seems to occur in a substantial proportion of patients with FD. The high accordance with LGE, reflecting cardiac dysfunction, suggests that cTNI-elevation can be a useful laboratory parameter for assessing myocardial damage in FD. [ABSTRACT FROM AUTHOR]