Determinants and prognostic implications of Cardiac Troponin T measured by a sensitive assay in Type 2 Diabetes Mellitus

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Hallén Jonas

2010-09-01

Full Text Available Abstract Background The cardiac troponins are biomarkers used for diagnosis of myocardial injury. They are also powerful prognostic markers in many diseases and settings. Recently introduced high-sensitivity assays indicate that chronic cardiac troponin elevations are common in response to cardiovascular (CV morbidity. Type 2 diabetes mellitus (T2DM confers a high risk of CV disease, but little is known about chronic cardiac troponin elevations in diabetic subjects. Accordingly, we aimed to understand the prevalence, determinants, and prognostic implications of cardiac troponin T (cTnT elevations measured with a high-sensitivity assay in patients with T2DM. Methods cTnT was measured in stored, frozen serum samples from 124 subjects enrolled in the Asker and Bærum Cardiovascular Diabetes trial at baseline and at 2-year follow-up, if availabe (96 samples available. Results were analyzed in relation to baseline variables, hospitalizations, and group assignment (multifactorial intensive versus conventional diabetes care for lowering CV risk. Results One-hundred thirteen (90 % had detectable cTnT at baseline and of those, 22 (18 % of the total population subjects had values above the 99th percentile for healthy controls (13.5 ng/L. Levels at baseline were associated with conventional CV risk factors (age, renal function, gender. There was a strong correlation between cTnT levels at the two time-points (r = 0.92, p > 0.001. Risk for hospitalizations during follow-up increased step-wise by quartiles of hscTnT measured at baseline (p = 0.058. Conclusions Elevations of cTnT above the 99th percentile measured by a highly sensitive assay were encountered frequently in a population of T2DM patients. cTnT levels appeared to be stable over time and associated with conventional CV risk factors. Although a clear trend was present, no statistically robust associations with adverse outcomes could be found.

Cardiaal troponine

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Mingels, A.M.; Gorgels, T.P.; van Dieijen-Visser, M.P.

2012-01-01

Measurement of cardiac troponins (cTnT and cTnI), the only cardiac specific biomarkers available, is the gold standard in diagnosing acute coronary syndrome. Due to the recent introduction of more sensitive methods i.e. the high-sensitivity troponin assays, the diagnostic cut-off concentrations have

Diagnostic and prognostic value of high-sensitivity cardiac troponin T in patients with syncope.

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Christ, Michael; Geier, Felicitas; Popp, Steffen; Singler, Katrin; Smolarsky, Alexander; Bertsch, Thomas; Müller, Christian; Greve, Yvonne

2015-02-01

We examined the diagnostic and predictive value of high-sensitivity cardiac troponin T (cTnThs) in patients with syncope. We performed an analysis of consecutive patients with syncope presenting to the emergency department. The primary end point was the accuracy to diagnose a cardiac syncope. In addition, the study explored the prognostic relevance of cTnThs in patients with cardiac and noncardiac syncope. A total of 360 patients were enrolled (median age, 70.5 years; male, 55.8%; 23.9% aged >80 years). Cardiac syncope was present in 22% of patients, reflex syncope was present in 40% of patients, syncope due to orthostatic hypotension was present in 20% of patients, and unexplained syncope was present in 17.5% of patients. A total of 148 patients (41%) had cTnThs levels above the 99% confidence interval (CI) (cutoff point). The diagnostic accuracy for cTnThs levels to determine the diagnosis of cardiac syncope was quantified by the area under the curve (0.77; CI, 0.72-0.83; P value of cTnThs levels within 30 days: Patients with increased cTnThs levels had a 52% likelihood for adverse events, patients with cTnThs levels below the cutoff point had a low risk (negative predictive value, 83.5%). Increased cTnThs levels indicate adverse prognosis in patients with noncardiac causes of syncope, but not in patients with cardiac syncope being a risk factor for adverse outcome by itself. Patients with syncope presenting to the emergency department have a high proportion of life-threatening conditions. cTnThs levels show a limited diagnostic and predictive accuracy for the identification of patients with syncope at high risk. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparison of cardiac troponins I and T measured with high-sensitivity methods for evaluation of prognosis in atrial fibrillation: an ARISTOTLE substudy.

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Hijazi, Ziad; Siegbahn, Agneta; Andersson, Ulrika; Lindahl, Bertil; Granger, Christopher B; Alexander, John H; Atar, Dan; Gersh, Bernard J; Hanna, Michael; Harjola, Veli-Pekka; Horowitz, John; Husted, Steen; Hylek, Elaine M; Lopes, Renato D; McMurray, John J V; Wallentin, Lars

2015-02-01

Although cardiac troponin is associated with outcomes in atrial fibrillation (AF), the complementary prognostic information provided by cardiac troponin I (cTnI) and cTnT is unknown. This study investigated the distribution, determinants, and prognostic value of cTnI and cTnT concentrations in patients with AF. Samples were collected. At the time of randomization, we analyzed cTnI and cTnT concentrations of 14806 AF patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial using high-sensitivity assays. Correlations (Spearman), determinants (multivariable linear regression), and outcomes (adjusted Cox models and c-statistics) were investigated. Concentrations of cTnI and cTnT were correlated (r = 0.70) and measurable in most participants [cTnI 98.5% (median 5.4 ng/L, ≥99th percentile in 9.2%) and cTnT 93.5% (median 10.9 ng/L, ≥99th percentile in 34.4%)]. Renal impairment was the most important factor affecting the concentrations of both troponins. cTnI increase was more associated with heart failure, vascular disease, and persistent/permanent AF, and cTnT with age, male sex, and diabetes. Over a median 1.9 years of follow-up, patients with both troponins above the median had significantly higher risk for stroke/systemic embolism [hazard ratio (HR) 1.72 (95% CI 1.31-2.27)], cardiac death [3.14 (2.35-4.20)], and myocardial infarction [2.99 (1.78-5.03)] than those with both troponins below median (all P Chemistry.

High-sensitivity cardiac troponin I assay to screen for acute rejection in patients with heart transplant.

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Patel, Parag C; Hill, Douglas A; Ayers, Colby R; Lavingia, Bhavna; Kaiser, Patricia; Dyer, Adrian K; Barnes, Aliessa P; Thibodeau, Jennifer T; Mishkin, Joseph D; Mammen, Pradeep P A; Markham, David W; Stastny, Peter; Ring, W Steves; de Lemos, James A; Drazner, Mark H

2014-05-01

A noninvasive biomarker that could accurately diagnose acute rejection (AR) in heart transplant recipients could obviate the need for surveillance endomyocardial biopsies. We assessed the performance metrics of a novel high-sensitivity cardiac troponin I (cTnI) assay for this purpose. Stored serum samples were retrospectively matched to endomyocardial biopsies in 98 cardiac transplant recipients, who survived ≥3 months after transplant. AR was defined as International Society for Heart and Lung Transplantation grade 2R or higher cellular rejection, acellular rejection, or allograft dysfunction of uncertain pathogenesis, leading to treatment for presumed rejection. cTnI was measured with a high-sensitivity assay (Abbott Diagnostics, Abbott Park, IL). Cross-sectional analyses determined the association of cTnI concentrations with rejection and International Society for Heart and Lung Transplantation grade and the performance metrics of cTnI for the detection of AR. Among 98 subjects, 37% had ≥1 rejection episode. cTnI was measured in 418 serum samples, including 35 paired to a rejection episode. cTnI concentrations were significantly higher in rejection versus nonrejection samples (median, 57.1 versus 10.2 ng/L; P<0.0001) and increased in a graded manner with higher biopsy scores (P(trend)<0.0001). The c-statistic to discriminate AR was 0.82 (95% confidence interval, 0.76-0.88). Using a cut point of 15 ng/L, sensitivity was 94%, specificity 60%, positive predictive value 18%, and negative predictive value 99%. A high-sensitivity cTnI assay seems useful to rule out AR in cardiac transplant recipients. If validated in prospective studies, a strategy of serial monitoring with a high-sensitivity cTnI assay may offer a low-cost noninvasive strategy for rejection surveillance. © 2014 American Heart Association, Inc.

Serial measurements of high sensitive cardiac troponin I in patients with acutely decompensated heart failure treated with carperitide or nitrates.

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Sato, Yukihito; Nishi, Kiyoto; Saijo, Sayaka; Tanada, Yohei; Goto, Taisuke; Takahashi, Naoki; Yamamoto, Erika; Fukuhara, Rei; Miyamoto, Tadashi; Taniguchi, Ryoji; Fujiwara, Hisayoshi; Takatsu, Yoshiki

2010-07-01

In patients with acutely decompensated heart failure (ADHF), elevated serum concentration of cardiac troponin is an independent predictor of adverse cardiac events. In ADHF with a preserved systolic blood pressure, treatment with intravenous vasodilator is recommended. However, the effect of vasodilators on troponin concentrations has not been elucidated well. Serial high sensitive cardiac troponin I (hs-TnI) was measured in 36 patients presenting with ADHF and preserved systolic blood pressure, of whom 20 were treated with atrial natriuretic peptide (ANP) and 16 with nitrates. The concentrations of hs-TnI ranged from 0.069+/-0.114ng/ml at baseline to 0.076+/-0.121ng/ml at 5h, 0.062+/-0.106ng/ml at 1 day, and 0.056+/-0.089ng/ml at day 7 (n=36,ns). The relative change in hs-TnI between baseline and at 5h, day 1 and day 7 were 1.13+/-0.43, 0.95+/-0.44 and 0.93+/-0.64 in patients treated with ANP, and 1.02+/-0.19, 0.95+/-0.31 and 1.19+/-1.38 in patients treated with nitrates (ns; ANP versus nitrates). On day 7, a hs-TnI change, >20% decrease from baseline, was observed in 55% patients with ANP versus 56% patients with nitrates (ns). The cardiac event rates were similar in both groups. In ADHF patients with preserved systolic blood pressure, the administration of intravenous vasodilators did not decrease hs-TnI over the first 7 days. Treatments with ANP and nitrates were associated with similar short-term decreases in hs-TnI and long-term adverse cardiac events. Copyright 2010 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Serum cardiac troponin I and cardiac troponin T concentrations in dogs with gastric dilatation-volvulus.

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Schober, Karsten E; Cornand, Corinna; Kirbach, Babett; Aupperle, Heike; Oechtering, Gerhard

2002-08-01

To determine whether serum concentrations of cardiac troponin I (cTnI) and cardiac troponin T (cTnT) are increased in dogs with gastric dilatationvolvulus (GDV) and whether concentrations correlate with severity of ECG abnormalities or outcome. Prospective case series. 85 dogs with GDV. Serum cTnl and cTnT concentrations were measured 12 to 24, 48, 72, and 96 hours after surgery. Dogs were grouped on the basis of severity of ECG abnormalities and outcome. cTnl and cTnT were detected in serum from 74 (87%) and 43 (51%) dogs, respectively. Concentrations were significantly different among groups when dogs were grouped on the basis of severity of ECG abnormalities (none or mild vs moderate vs severe). Dogs that died (n = 16) had significantly higher serum cTnI (24.9 ng/ml) and cTnT (0.18 ng/ml) concentrations than did dogs that survived (2.05 and dogs with high serum cardiac troponin concentrations. Results indicate that concentrations of cTnI and cTnT suggestive of myocardial cell injury can commonly be found in serum from dogs with GDV and that serum cardiac troponin concentrations are associated with severity of ECG abnormalities and outcome.

Elevated Cardiac Troponin T in Patients With Skeletal Myopathies.

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Schmid, Johannes; Liesinger, Laura; Birner-Gruenberger, Ruth; Stojakovic, Tatjana; Scharnagl, Hubert; Dieplinger, Benjamin; Asslaber, Martin; Radl, Roman; Beer, Meinrad; Polacin, Malgorzata; Mair, Johannes; Szolar, Dieter; Berghold, Andrea; Quasthoff, Stefan; Binder, Josepha S; Rainer, Peter P

2018-04-10

Cardiac troponins are often elevated in patients with skeletal muscle disease who have no evidence of cardiac disease. The goal of this study was to characterize cardiac troponin concentrations in patients with myopathies and derive insights regarding the source of elevated troponin T measurements. Cardiac troponin T (cTnT) and cardiac troponin I (cTnI) concentrations were determined by using high sensitivity assays in 74 patients with hereditary and acquired skeletal myopathies. Patients underwent comprehensive cardiac evaluation, including 12-lead electrocardiogram, 24-h electrocardiogram, cardiac magnetic resonance imaging, and coronary artery computed tomography. cTnT and cTnI protein expression was determined in skeletal muscle samples of 9 patients and in control tissues derived from autopsy using antibodies that are used in commercial assays. Relevant Western blot bands were subjected to liquid chromatography tandem mass spectrometry for protein identification. Levels of cTnT (median: 24 ng/l; interquartile range: 11 to 54 ng/l) were elevated (>14 ng/l) in 68.9% of patients; cTnI was elevated (>26 ng/l) in 4.1% of patients. Serum cTnT levels significantly correlated with creatine kinase and myoglobin (r = 0.679 and 0.786, respectively; both p < 0.001). Based on cTnT serial testing, 30.1% would have fulfilled current rule-in criteria for myocardial infarction. Noncoronary cardiac disease was present in 23%. Using cTnT antibodies, positive bands were found in both diseased and healthy skeletal muscle at molecular weights approximately 5 kDa below cTnT. Liquid chromatography tandem mass spectrometry identified the presence of skeletal troponin T isoforms in these bands. Measured cTnT concentrations were chronically elevated in the majority of patients with skeletal myopathies, whereas cTnI elevation was rare. Our data indicate that cross-reaction of the cTnT immunoassay with skeletal muscle troponin isoforms was the likely cause. Copyright © 2018 The

The clinical utility of lipid profile and positive troponin in predicting future cardiac events

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Arun Kumar

2012-02-01

Full Text Available Objective: To study the usefulness of traditional lipid profile levels in screening subjects who had developed chest pain due to cardiac event as indicated by a positive troponin I (TnI test. Methods: In this retrospective study data of the 740 patients presented to the emergency department with symptoms of cardiac ischemia that underwent both troponin and lipid profiles tests were compared with the lipid profiles of 411 normal healthy subjects (controls. The troponin was detected qualitatively when a specimen contains TnI above the 99th percentile (TnI >0.5 ng/ mL. The total cholesterol (TC, high density lipoproteins (HDL, very low density lipoproteins (VLDL, and triacyl glycerol (TG levels were also analyzed and low density lipoprotein level (LDL was calculated using Friedewald ’s formula. Results: Patients with chest pain and positive troponin test (with confirmed cardiac event were found to have significantly elevated levels of TC, TG, LDL and significantly reduced HDL levels when compared to the patients who experienced only chest pain (negative troponin and healthy controls. Conclusions: Traditional lipid profile levels still can be used in screening populations to identify the subjects with high risk of developing cardiac event which is identified by highly sensitive and specific positive troponin test.

Influence of population selection on the 99th percentile reference value for cardiac troponin assays.

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Collinson, Paul O; Heung, Yen Ming; Gaze, David; Boa, Frances; Senior, Roxy; Christenson, Robert; Apple, Fred S

2012-01-01

We sought to determine the effect of patient selection on the 99th reference percentile of 2 sensitive and 1 high-sensitivity (hs) cardiac troponin assays in a well-defined reference population. Individuals>45 years old were randomly selected from 7 representative local community practices. Detailed information regarding the participants was collected via questionnaires. The healthy reference population was defined as individuals who had no history of vascular disease, hypertension, or heavy alcohol intake; were not receiving cardiac medication; and had blood pressure60 mL·min(-1)·(1.73 m2)(-1), and normal cardiac function according to results of echocardiography. Samples were stored at -70 °C until analysis for cardiac troponin I (cTnI) and cardiac troponin T (cTnT) and N-terminal pro-B-type natriuretic peptide. Application of progressively more stringent population selection strategies to the initial baseline population of 545 participants until the only individuals who remained were completely healthy according to the study criteria reduced the number of outliers seen and led to a progressive decrease in the 99th-percentile value obtained for the Roche hs-cTnT assay and the sensitive Beckman cTnI assay but not for the sensitive Siemens Ultra cTnI assay. Furthermore, a sex difference found in the baseline population for the hs-cTnT (P=0.0018) and Beckman cTnI assays (Pstrategy significantly influenced the 99th percentile reference values determined for troponin assays and the observed sex differences in troponin concentrations.

Evaluation of analytical performance of a new high-sensitivity immunoassay for cardiac troponin I.

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Masotti, Silvia; Prontera, Concetta; Musetti, Veronica; Storti, Simona; Ndreu, Rudina; Zucchelli, Gian Carlo; Passino, Claudio; Clerico, Aldo

2018-02-23

The study aim was to evaluate and compare the analytical performance of the new chemiluminescent immunoassay for cardiac troponin I (cTnI), called Access hs-TnI using DxI platform, with those of Access AccuTnI+3 method, and high-sensitivity (hs) cTnI method for ARCHITECT platform. The limits of blank (LoB), detection (LoD) and quantitation (LoQ) at 10% and 20% CV were evaluated according to international standardized protocols. For the evaluation of analytical performance and comparison of cTnI results, both heparinized plasma samples, collected from healthy subjects and patients with cardiac diseases, and quality control samples distributed in external quality assessment programs were used. LoB, LoD and LoQ at 20% and 10% CV values of the Access hs-cTnI method were 0.6, 1.3, 2.1 and 5.3 ng/L, respectively. Access hs-cTnI method showed analytical performance significantly better than that of Access AccuTnI+3 method and similar results to those of hs ARCHITECT cTnI method. Moreover, the cTnI concentrations measured with Access hs-cTnI method showed close linear regressions with both Access AccuTnI+3 and ARCHITECT hs-cTnI methods, although there were systematic differences between these methods. There was no difference between cTnI values measured by Access hs-cTnI in heparinized plasma and serum samples, whereas there was a significant difference between cTnI values, respectively measured in EDTA and heparin plasma samples. Access hs-cTnI has analytical sensitivity parameters significantly improved compared to Access AccuTnI+3 method and is similar to those of the high-sensitivity method using ARCHITECT platform.

FET-biosensor for cardiac troponin biomarker

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Md Arshad Mohd Khairuddin

2017-01-01

Full Text Available Acute myocardial infarction or myocardial infarction (MI is a major health problem, due to diminished flow of blood to the heart, leads to higher rates of mortality and morbidity. The most specific markers for cardiac injury are cardiac troponin I (cTnI and cardiac troponin T (cTnT which have been considered as ‘gold standard’. Due to higher specificity, determination of the level of cardiac troponins became a predominant indicator for MI. Currently, field-effect transistor (FET-based biosensors have been main interest to be implemented in portable sensors with the ultimate application in point-of-care testing (POCT. In this paper, we review on the FET-based biosensor based on its principle of operation, integration with nanomaterial, surface functionalization as well as immobilization, and the introduction of additional gate (for ambipolar conduction on the device architecture for the detection of cardiac troponin I (cTnI biomarker.

Prognostic implications of high-sensitivity cardiac troponin T assay in a real-world population with non-ST-elevation acute coronary syndrome.

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Magnoni, Marco; Gallone, Guglielmo; Ceriotti, Ferruccio; Vergani, Vittoria; Giorgio, Daniela; Angeloni, Giulia; Maseri, Attilio; Cianflone, Domenico

2018-09-01

High-sensitivity cardiac troponin T (hsTnT) was recently approved for clinical use by the Food and Drug Administration. The transition from contemporary to hsTnT assays requires a thorough understanding of the clinical differences between these assays. HsTnT may provide a more accurate prognostic stratification than contemporary cardiac troponin I (cTnI) in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). HsTnT and cTnI were measured in 644 patients with CK-MB negative NSTE-ACS who were enrolled in the prospective multicenter SPAI (Stratificazione Prognostica dell'Angina Instabile) study. Patients were stratified at the 99th percentile reference limit for each assay. The primary endpoint was cardiovascular death (CVD) or non-fatal myocardial infarction (MI); the secondary endpoint was the occurrence of unstable angina (UA). Follow-up lasted 180 days. Patients with hsTnT ≥99th percentile were at higher risk of CVD/MI (30-day: 5.9% vs 0.8%, p  = 0.001; 180-day: 11.1% vs 4.7%, p  = 0.004), also after adjusting for TIMI Risk Score. No significant difference in CVD/MI at 180-day was found between hsTnT-positive/cTnI-negative and hsTnT-negative/cTnI-negative patients (adjHR 1.61, 95% CI 0.74-3.49, p  = 0.232). Occurrence of UA was not differently distributed between hsTnT groups dichotomized at the 99th percentile (12.4% vs 12.5% p  = 0.54). Our investigation on a real-world NSTE-ACS population showed good prognostic performance of hsTnT in the risk stratification of the hard endpoint, but did not demonstrate the improved prognostic ability of hsTnT over contemporary cTn. Neither troponin assay predicted the recurrence of UA, suggesting the acute rise of cardiac troponin as a marker of severity, but not the occurrence of future coronary instability.

Progression in sensing cardiac troponin biomarker charge transductions on semiconducting nanomaterials

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Fathil, M.F.M., E-mail: faris.fathil@gmail.com [Institute of Nano Electronic Engineering (INEE), Universiti Malaysia Perlis, 01000, Kangar, Perlis (Malaysia); Md Arshad, M.K., E-mail: mohd.khairuddin@unimap.edu.my [Institute of Nano Electronic Engineering (INEE), Universiti Malaysia Perlis, 01000, Kangar, Perlis (Malaysia); School of Microelectronic Engineering, Universiti Malaysia Perlis, 01000, Kangar, Perlis (Malaysia); Ruslinda, A.R., E-mail: ruslinda@unimap.edu.my [Institute of Nano Electronic Engineering (INEE), Universiti Malaysia Perlis, 01000, Kangar, Perlis (Malaysia); Nuzaihan, M.N.M., E-mail: m.nuzaihan@unimap.edu.my [Institute of Nano Electronic Engineering (INEE), Universiti Malaysia Perlis, 01000, Kangar, Perlis (Malaysia); Gopinath, Subash C.B., E-mail: subash@unimap.edu.my [Institute of Nano Electronic Engineering (INEE), Universiti Malaysia Perlis, 01000, Kangar, Perlis (Malaysia); School of Bioprocess Engineering, Universiti Malaysia Perlis, 02600, Arau, Perlis (Malaysia); Adzhri, R., E-mail: adzhri@gmail.com [Institute of Nano Electronic Engineering (INEE), Universiti Malaysia Perlis, 01000, Kangar, Perlis (Malaysia); Hashim, U., E-mail: uda@unimap.edu.my [Institute of Nano Electronic Engineering (INEE), Universiti Malaysia Perlis, 01000, Kangar, Perlis (Malaysia); School of Microelectronic Engineering, Universiti Malaysia Perlis, 01000, Kangar, Perlis (Malaysia)

2016-09-07

A real-time ability to interpret the interaction between targeted biomolecules and the surface of semiconductors (metal transducers) into readable electrical signals, without biomolecular modification involving fluorescence dyes, redox enzymes, and radioactive labels, created by label-free biosensors has been extensively researched. Field-effect transistor (FET)- and capacitor-based biosensors are among the diverse electrical charge biosensing architectures that have drawn much attention for having charge transduction; thus, enabling the early and rapid diagnosis of the appropriate cardiac biomarkers at lower concentrations. These semiconducting material-based transducers are very suitable to be integrated with portable electronic devices for future online collection, transmission, reception, analysis, and reporting. This overview elucidates and clarifies two major electrical label-free systems (FET- and capacitor-based biosensors) with cardiac troponin (cTn) biomarker-mediated charge transduction for acute myocardial infarction (AMI) diagnosis. Advances in these systems are highlighted by their progression in bridging the laboratory and industry; the foremost technologies have made the transition from benchtop to bedside and beyond. - Highlights: • The progression of cardiac troponin detection from past to future are presented. • Electrical label-free biosensors for cardiac troponin are discussed. • The discussion focused on field-effect transistor-and capacitor-based devices. • Surface functionalization, sensitivity, and innovation of devices are highlighted. • They presented high sensitivity and specificity of real-time AMI determination.

Selectivity verification of cardiac troponin monoclonal antibodies for cardiac troponin detection by using conventional ELISA

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Fathil, M. F. M.; Arshad, M. K. Md; Gopinath, Subash C. B.; Adzhri, R.; Ruslinda, A. R.; Hashim, U.

2017-03-01

This paper presents preparation and characterization of conventional enzyme-linked immunosorbent assay (ELISA) for cardiac troponin detection to determine the selectivity of the cardiac troponin monoclonal antibodies. Monoclonal antibodies, used to capture and bind the targets in this experiment, are cTnI monoclonal antibody (MAb-cTnI) and cTnT monoclonal antibody (MAb-cTnT), while both cardiac troponin I (cTnI) and T (cTnT) are used as targets. ELISA is performed inside two microtiter plates for MAb-cTnI and MAb-cTnT. For each plate, monoclonal antibodies are tested by various concentrations of cTnI and cTnT ranging from 0-6400 µg/l. The binding selectivity and level of detection between monoclonal antibodies and antigen are determined through visual observation based on the color change inside each well on the plate. ELISA reader is further used to quantitatively measured the optical density of the color changes, thus produced more accurate reading. The results from this experiment are utilized to justify the use of these monoclonal antibodies as bio-receptors for cardiac troponin detection by using field-effect transistor (FET)-based biosensors coupled with substrate-gate in the future.

European multicenter analytical evaluation of the Abbott ARCHITECT STAT high sensitive troponin I immunoassay.

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Krintus, Magdalena; Kozinski, Marek; Boudry, Pascal; Capell, Nuria Estañ; Köller, Ursula; Lackner, Karl; Lefèvre, Guillaume; Lennartz, Lieselotte; Lotz, Johannes; Herranz, Antonio Mora; Nybo, Mads; Plebani, Mario; Sandberg, Maria B; Schratzberger, Wolfgang; Shih, Jessie; Skadberg, Øyvind; Chargui, Ahmed Taoufik; Zaninotto, Martina; Sypniewska, Grazyna

2014-11-01

International recommendations highlight the superior value of cardiac troponins (cTns) for early diagnosis of myocardial infarction along with analytical requirements of improved precision and detectability. In this multicenter study, we investigated the analytical performance of a new high sensitive cardiac troponin I (hs-cTnI) assay and its 99th percentile upper reference limit (URL). Laboratories from nine European countries evaluated the ARCHITECT STAT high sensitive troponin I (hs-TnI) immunoassay on the ARCHITECT i2000SR/i1000SR immunoanalyzers. Imprecision, limit of blank (LoB), limit of detection (LoD), limit of quantitation (LoQ) linearity of dilution, interferences, sample type, method comparisons, and 99th percentile URLs were evaluated in this study. Total imprecision of 3.3%-8.9%, 2.0%-3.5% and 1.5%-5.2% was determined for the low, medium and high controls, respectively. The lowest cTnI concentration corresponding to a total CV of 10% was 5.6 ng/L. Common interferences, sample dilution and carryover did not affect the hs-cTnI results. Slight, but statistically significant, differences with sample type were found. Concordance between the investigated hs-cTnI assay and contemporary cTnI assay at 99th percentile cut-off was found to be 95%. TnI was detectable in 75% and 57% of the apparently healthy population using the lower (1.1 ng/L) and upper (1.9 ng/L) limit of the LoD range provided by the ARCHITECT STAT hs-TnI package insert, respectively. The 99th percentile values were gender dependent. The new ARCHITECT STAT hs-TnI assay with improved analytical features meets the criteria of high sensitive Tn test and will be a valuable diagnostic tool.

Cross-sectional study of high-sensitivity cardiac troponins T and I in a hospital and community outpatient setting.

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Potter, Julia M; Simpson, Aaron J; Kerrigan, Jennifer; Southcott, Emma; Salib, Marie M; Koerbin, Gus; Hickman, Peter E

2017-02-01

Cardiac troponins are specific for the heart, but not for the acute coronary syndrome. We wanted to assess how common elevated cardiac troponin concentrations were, in a population with significant non-cardiac disease. We measured both hs-cTnT and hs-cTnI on all samples submitted to the laboratory during one 24h period, and assessed the magnitude of the cTn concentration with the location and severity of disease of the patient. Community patients and patients from the maternity ward had the lowest cTn concentrations with results above the 99th percentile being only 0-2% of the total. As expected, the highest proportion of results >99th percentile came from Coronary Care and Intensive Care. However, substantial numbers of persons on Medical and Surgical wards, without a primary diagnosis of cardiac disease, also had cTn >99th percentile. Particularly for cTnT, there was a highly significant odds ratio predicting mortality when results above and below the 99th percentile were compared. Significant illnesses apart from the acute coronary syndrome are important causes of a rise in cTn to above the 99th percentile, and appear to reflect the total body burden of disease. Even when the high hs-cTn concentration is not due to the acute coronary syndrome, there is a significant association with all-cause mortality. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Validation of the (Troponin-only) Manchester ACS decision aid with a contemporary cardiac troponin I assay.

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Va Den Berg, Patricia; Burrows, Gillian; Lewis, Philip; Carley, Simon; Body, Richard

2018-04-01

The Manchester Acute Coronary Syndromes (MACS) decision aid can 'rules in' and 'rule out' acute coronary syndromes (ACS) by combining a patient's symptoms with the results of a single blood test taken at the time of arrival in the Emergency Department (ED). The original model (MACS) included two biomarkers: high sensitivity cardiac troponin T (hs-cTnT) and heart-type fatty acid binding protein (h-FABP). A refined model without h-FABP was found to have comparable sensitivity but greater specificity. We sought to validate MACS and T-MACS using the contemporary Siemens Advia Centaur cardiac troponin I assay to increase usability in practice. This is a secondary analysis from prospective diagnostic cohort study at Stepping Hill Hospital, United Kingdom. Patients presenting with chest pain of suspected cardiac nature warranting rule out for ACS were included. All patients underwent hs-cTnT testing at least 12h after peak symptoms. The primary outcome was a diagnosis of ACS, defined as either prevalent acute myocardial infarction (AMI) or incident major adverse cardiac events (death, AMI or coronary revascularization) within 30days. Of 405 included patients, 76 (18.8%) had ACS. MACS and T-MACS had similar C-statistics (0.94 for each, p=0.36) and sensitivity (difference 1.3%, 95% CI -1.3 to 3.9%, p=1.00) but T-MACS had significantly greater specificity (difference 16.7%, 95% CI 14.6-18.9%, p<0.0001). T-MACS and MACS would have allowed 36.3% and 22.5% patients to be immediately discharged respectively. Of patients classified as 'very low risk', none had ACS when MACS was used compared to one (0.7%) with T-MACS. Both MACS and T-MACS effectively ruled out ACS even with a contemporary troponin I assay and could be used to reduce unnecessary hospital admissions. Copyright © 2017. Published by Elsevier Inc.

Effect of antioxidant supplementation on exercise-induced cardiac troponin release in cyclists: a randomized trial.

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Klinkenberg, Lieke J J; Res, Peter T; Haenen, Guido R; Bast, Aalt; van Loon, Luc J C; van Dieijen-Visser, Marja P; Meex, Steven J R

2013-01-01

Cardiac troponin is the biochemical gold standard to diagnose acute myocardial infarction. Interestingly however, elevated cardiac troponin concentrations are also frequently observed during and after endurance-type exercise. Oxidative stress associated with prolonged exercise has been proposed to contribute to cardiac troponin release. Therefore, the aim of this study was to assess the effect of 4 week astaxanthin supplementation (a potent cartenoid antioxidant) on antioxidant capacity and exercise-induced cardiac troponin release in cyclists. Thirty-two well-trained male cyclists (age 25±5, weight 73±7 kg, maximum O2 uptake 60±5 mL·kg(-1)·min(-1), Wmax 5.4±0.5 W·kg(-1); mean ± SD) were repeatedly subjected to a laboratory based standardized exercise protocol before and after 4 weeks of astaxanthin (20 mg/day), or placebo supplementation in a double-blind randomized manner. Blood samples were obtained at baseline, at 60 min of cycling and immediately post-exercise (≈ 120 min). The pre-supplementation cycling trial induced a significant rise of median cardiac troponin T concentrations from 3.2 (IQR 3.0-4.2) to 4.7 ng/L (IQR 3.7-6.7), immediately post-exercise (pexercise-induced cardiac troponin T release (p = 0.24), as measured by the incremental area under the curve. Furthermore, the elevation in basal plasma astaxanthin concentrations was not reflected in changes in antioxidant capacity markers (trolox equivalent antioxidant capacity, uric acid, and malondialdehyde). Markers of inflammation (high-sensitivity C-reactive protein) and exercise-induced skeletal muscle damage (creatine kinase) were equally unaffected by astaxanthin supplementation. Despite substantial increases in plasma astaxanthin concentrations, astaxanthin supplementation did not improve antioxidant capacity in well-trained cyclists. Accordingly, exercise-induced cardiac troponin T concentrations were not affected by astaxanthin supplementation. ClinicalTrials.gov NCT01241877.

Dynamic Equilibrium of Cardiac Troponin C's Hydrophobic Cleft and Its Modulation by Ca2+ Sensitizers and a Ca2+ Sensitivity Blunting Phosphomimic, cTnT(T204E).

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Schlecht, William; Dong, Wen-Ji

2017-10-18

Several studies have suggested that conformational dynamics are important in the regulation of thin filament activation in cardiac troponin C (cTnC); however, little direct evidence has been offered to support these claims. In this study, a dye homodimerization approach is developed and implemented that allows the determination of the dynamic equilibrium between open and closed conformations in cTnC's hydrophobic cleft. Modulation of this equilibrium by Ca 2+ , cardiac troponin I (cTnI), cardiac troponin T (cTnT), Ca 2+ -sensitizers, and a Ca 2+ -desensitizing phosphomimic of cTnT (cTnT(T204E) is characterized. Isolated cTnC contained a small open conformation population in the absence of Ca 2+ that increased significantly upon the addition of saturating levels of Ca 2+ . This suggests that the Ca 2+ -induced activation of thin filament arises from an increase in the probability of hydrophobic cleft opening. The inclusion of cTnI increased the population of open cTnC, and the inclusion of cTnT had the opposite effect. Samples containing Ca 2+ -desensitizing cTnT(T204E) showed a slight but insignificant decrease in open conformation probability compared to samples with cardiac troponin T, wild type [cTnT(wt)], while Ca 2+ sensitizer treated samples generally increased open conformation probability. These findings show that an equilibrium between the open and closed conformations of cTnC's hydrophobic cleft play a significant role in tuning the Ca 2+ sensitivity of the heart.

Preprocedural High-Sensitivity Cardiac Troponin T and Clinical Outcomes in Patients With Stable Coronary Artery Disease Undergoing Elective Percutaneous Coronary Intervention.

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Zanchin, Thomas; Räber, Lorenz; Koskinas, Konstantinos C; Piccolo, Raffaele; Jüni, Peter; Pilgrim, Thomas; Stortecky, Stefan; Khattab, Ahmed A; Wenaweser, Peter; Bloechlinger, Stefan; Moschovitis, Aris; Frenk, Andre; Moro, Christina; Meier, Bernhard; Fiedler, Georg M; Heg, Dik; Windecker, Stephan

2016-06-01

Cardiac troponin detected by new-generation, highly sensitive assays predicts clinical outcomes among patients with stable coronary artery disease (SCAD) treated medically. The prognostic value of baseline high-sensitivity cardiac troponin T (hs-cTnT) elevation in SCAD patients undergoing elective percutaneous coronary interventions is not well established. This study assessed the association of preprocedural levels of hs-cTnT with 1-year clinical outcomes among SCAD patients undergoing percutaneous coronary intervention. Between 2010 and 2014, 6974 consecutive patients were prospectively enrolled in the Bern Percutaneous Coronary Interventions Registry. Among patients with SCAD (n=2029), 527 (26%) had elevated preprocedural hs-cTnT above the upper reference limit of 14 ng/L. The primary end point, mortality within 1 year, occurred in 20 patients (1.4%) with normal hs-cTnT versus 39 patients (7.7%) with elevated baseline hs-cTnT (P<0.001). Patients with elevated hs-cTnT had increased risks of all-cause (hazard ratio 5.73; 95% confidence intervals 3.34-9.83; P<0.001) and cardiac mortality (hazard ratio 4.68; 95% confidence interval 2.12-10.31; P<0.001). Preprocedural hs-TnT elevation remained an independent predictor of 1-year mortality after adjustment for relevant risk factors, including age, sex, and renal failure (adjusted hazard ratio 2.08; 95% confidence interval 1.10-3.92; P=0.024). A graded mortality risk was observed across higher tertiles of elevated preprocedural hs-cTnT, but not among patients with hs-cTnT below the upper reference limit. Preprocedural elevation of hs-cTnT is observed in one fourth of SCAD patients undergoing elective percutaneous coronary intervention. Increased levels of preprocedural hs-cTnT are proportionally related to the risk of death and emerged as independent predictors of all-cause mortality within 1 year. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02241291. © 2016 American Heart Association, Inc.

Clinical Use of Ultrasensitive Cardiac Troponin I Assay in Intermediate- and High-Risk Surgery Patients

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Flávia Kessler Borges

2013-01-01

Full Text Available Background. Cardiac troponin levels have been reported to add value in the detection of cardiovascular complications in noncardiac surgery. A sensitive cardiac troponin I (cTnI assay could provide more accurate prognostic information. Methods. This study prospectively enrolled 142 patients with at least one Revised Cardiac Risk Index risk factor who underwent noncardiac surgery. cTnI levels were measured postoperatively. Short-term cardiac outcome predictors were evaluated. Results. cTnI elevation was observed in 47 patients, among whom 14 were diagnosed as having myocardial infarction (MI. After 30 days, 16 patients had major adverse cardiac events (MACE. Excluding patients with a final diagnosis of MI, predictors of cTnI elevation included dialysis, history of heart failure, transoperative major bleeding, and elevated levels of pre- and postoperative N-terminal pro-B-type natriuretic peptide (NT-proBNP. Maximal cTnI values showed the highest sensitivity (94%, specificity (75%, and overall accuracy (AUC 0.89; 95% CI 0.80–0.98 for postoperative MACE. Postoperative cTnI peak level (OR 9.4; 95% CI 2.3–39.2 and a preoperative NT-proBNP level ≥917 pg/mL (OR 3.47; 95% CI 1.05–11.6 were independent risk factors for MACE. Conclusions. cTnI was shown to be an independent prognostic factor for cardiac outcomes and should be considered as a component of perioperative risk assessment.

DIAGNOSTIC EFFICACY OF CARDIAC TROPONIN-T IN ACUTE MYOCARDIAL INFARCTION PATIENTS ADMITTED IN INTENSIVE CARDIAC CARE UNIT

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Tapan

2016-03-01

Full Text Available INTRODUCTION Myocardial infarction is a common and severe manifestation of ischaemic heart disease (IHD. Acute myocardial infarction (AMI is the result of death of heart muscle cells following either from a prolonged or severe ischaemia. The World Health Organisation emphasises IHD as our "Modern Epidemic" and AMI as common cause of sudden death. AIM The present study has been undertaken with the aim to assess the role of cardiac Troponin-T in early diagnosis of AMI and to evaluate its positive roles over CK-MB and LDH enzyme assays. The study also aims to find out the role of cardiac Troponin-T test, where ECG changes are nondiagnostic and inconclusive for AMI. MATERIAL & METHOD One hundred cases of provisionally diagnosed AMI, who were admitted during June 2012 to July 2015 in ICC Unit of TMC & Dr. BRAM Teaching Hospital, formed the subjects for the study. Those patients reported 2 to 10 hours after onset of chest pain were included in this study. Patients reported beyond 10 hours after onset of chest pain of AMI cases and patients having chest pain of non-AMI causes are excluded from the study. The provisional diagnosis of AMI was done on the basis of the history, chest pain, clinical findings and ECG changes. Trop-T test (Troponin-T sensitive rapid test by Muller Bardoff, et al, 1991 as well as CK-MB (creatine kinase-MB isoenzymeassays were performed immediately for each and every patient. Trop-T test was repeated in some selective cases where the early changes were insignificant and the results were compared with those of CK-MB, at different period of the disease onset. RESULTS The rapid cardiac Troponin-T test (CTn-T has 100% specificity for AMI whereas CK-MB and LDH have specificities of 80% and 60% respectively. The CTn-T has diagnostic efficiency of 92% for AMI but ECG has only 69% sensitivity and 80% specificity. The overall diagnostic efficacy of cardiac Troponin-T is higher than that of CK-MB, LDH and ECG (94% versus 92%, 91 % and 72

Effect of antioxidant supplementation on exercise-induced cardiac troponin release in cyclists: a randomized trial.

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Lieke J J Klinkenberg

Full Text Available Cardiac troponin is the biochemical gold standard to diagnose acute myocardial infarction. Interestingly however, elevated cardiac troponin concentrations are also frequently observed during and after endurance-type exercise. Oxidative stress associated with prolonged exercise has been proposed to contribute to cardiac troponin release. Therefore, the aim of this study was to assess the effect of 4 week astaxanthin supplementation (a potent cartenoid antioxidant on antioxidant capacity and exercise-induced cardiac troponin release in cyclists.Thirty-two well-trained male cyclists (age 25±5, weight 73±7 kg, maximum O2 uptake 60±5 mL·kg(-1·min(-1, Wmax 5.4±0.5 W·kg(-1; mean ± SD were repeatedly subjected to a laboratory based standardized exercise protocol before and after 4 weeks of astaxanthin (20 mg/day, or placebo supplementation in a double-blind randomized manner. Blood samples were obtained at baseline, at 60 min of cycling and immediately post-exercise (≈ 120 min.The pre-supplementation cycling trial induced a significant rise of median cardiac troponin T concentrations from 3.2 (IQR 3.0-4.2 to 4.7 ng/L (IQR 3.7-6.7, immediately post-exercise (p<0.001. Four weeks of astaxanthin supplementation significantly increased mean basal plasma astaxanthin concentrations from non-detectable values to 175±86 µg·kg(-1. However, daily astaxanthin supplementation had no effect on exercise-induced cardiac troponin T release (p = 0.24, as measured by the incremental area under the curve. Furthermore, the elevation in basal plasma astaxanthin concentrations was not reflected in changes in antioxidant capacity markers (trolox equivalent antioxidant capacity, uric acid, and malondialdehyde. Markers of inflammation (high-sensitivity C-reactive protein and exercise-induced skeletal muscle damage (creatine kinase were equally unaffected by astaxanthin supplementation.Despite substantial increases in plasma astaxanthin concentrations

Early diagnosis of myocardial infarction using absolute and relative changes in cardiac troponin concentrations.

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Irfan, Affan; Reichlin, Tobias; Twerenbold, Raphael; Meister, Marc; Moehring, Berit; Wildi, Karin; Bassetti, Stefano; Zellweger, Christa; Gimenez, Maria Rubini; Hoeller, Rebeca; Murray, Karsten; Sou, Seoung Mann; Mueller, Mira; Mosimann, Tamina; Reiter, Miriam; Haaf, Philip; Ziller, Ronny; Freidank, Heike; Osswald, Stefan; Mueller, Christian

2013-09-01

Absolute changes in high-sensitivity cardiac troponin T (hs-cTnT) seem to have higher diagnostic accuracy in the early diagnosis of acute myocardial infarction compared with relative changes. It is unknown whether the same applies to high-sensitivity cardiac troponin I (hs-cTnI) assays and whether the combination of absolute and relative change might further increase accuracy. In a prospective, international multicenter study, high-sensitivity cardiac troponin (hs-cTn) was measured with 3 novel assays (hs-cTnT, Roche Diagnostics Corp, Indianapolis, Ind; hs-cTnI, Beckman Coulter Inc, Brea, Calif; hs-cTnI, Siemens, Munich, Germany) in a blinded fashion at presentation and after 1 and 2 hours in a blinded fashion in 830 unselected patients with suspected acute myocardial infarction. The final diagnosis was adjudicated by 2 independent cardiologists. The area under the receiver operating characteristic curve for diagnosing acute myocardial infarction was significantly higher for 1- and 2-hour absolute versus relative hs-cTn changes for all 3 assays (P Siemens, 0.96 [95% CI, 0.93-0.99]) were high and provided some benefit compared with the use of absolute change alone for hs-cTnT, but not for the hs-cTnI assays. Reclassification analysis confirmed the superiority of absolute changes versus relative changes. Absolute changes seem to be the preferred metrics for both hs-cTnT and hs-cTnI in the early diagnosis of acute myocardial infarction. The combination of absolute and relative changes provides a small added value for hs-cTnT, but not for hs-cTnI. Copyright © 2013 Elsevier Inc. All rights reserved.

Self-reported cocaine use is not associated with elevations in high-sensitivity troponin I.

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Jordan, Candice D; Korley, Frederick K; Stolbach, Andrew I

2017-06-01

High-sensitivity troponin (hsTn) assays detect 10 times lower concentrations of cardiac troponin than conventional assays. We examined the effects of self-reported cocaine use to determine whether those with acute cocaine use being evaluated for ACS are more likely to have elevated hsTnI than those nonusers being evaluated for ACS. We conducted a sub-analysis of a prospective cohort of ED patients evaluated for acute coronary syndrome. Recent cocaine use was determined by structured patient interviews. High-sensitivity troponin (Abbott) and conventional troponin I (Abbott, cTnI) were measured on samples drawn at presentation. Urine toxicology screen for cocaine metabolite was obtained at the discretion of treating clinicians. Of 1862 patients enrolled, 444 reported prior cocaine use and 99 reported cocaine use within the preceding month. Median hsTn in patients with last cocaine use within 24 h, 2-7 days, 1 week-1 month, >1 month, and no prior cocaine use were: 9 (IQR: 3-17) ng/L, 6 (IQR: 3-24.3) ng/L, 6 (IQR: 3-89.5) ng/L, 3 (IQR: 3-18.5) ng/L and 3 (IQR: 3-17) ng/L, respectively. Urine toxicology assays (UTox) for cocaine were performed in 640 (34.4%) patients. The median hsTn for those who were UTox+, UTox - and those without a UTox were: 9 ng/L (IQR: 3-48.5), 9 ng/L (IQR: 3-40) and 3 ng/L (IQR: 3-12), respectively. There were no differences in the prevalence of new troponin elevations (hsTn >99th percentile but cTnI cocaine use compared to those without recent cocaine use. In this first investigation of hsTn in patients with self-reported recent cocaine use, we have determined that hsTn does not lead to an increase in the prevalence of troponin elevation in cocaine users.

Plasma Levels of High Sensitivity Cardiac Troponin T in Adults with Repaired Tetralogy of Fallot

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Lai, Clare T. M.; Wong, Sophia J.; Ip, Janice J. K.; Wong, Wai-keung; Tsang, Kwong-cheong; Lam, Wendy W. M.; Cheung, Yiu-fai

2015-01-01

Detectable low circulating level of cardiac troponin T (cTnT) may reflect subclinical myocardial injury. We tested the hypothesis that circulating levels of hs-cTnT are altered in adults with repaired tetralogy of Fallot (TOF) and associated with ventricular volume load and function. Eighty-eight TOF patients and 48 controls were studied. Plasma hs-cTnT levels were determined using a highly sensitive assay (hs-cTnT). The right (RV) and left ventricular (LV) volumes and ejection fraction (EF) were measured using 3D echocardiography and, in 52 patients, cardiac magnetic resonance (CMR). The median (interquartile range) for male and female patients were 4.87 (3.83–6.62) ng/L and 3.11 (1.00–3.87) ng/L, respectively. Thirty percent of female but none of the male patients had increased hs-cTnT levels. Female patients with elevated hs-cTnT levels, compared to those without, had greater RV end-diastolic and end-systolic volumes and LV systolic dyssynchrony index (all p < 0.05). For patient cohort only, hs-cTnT levels correlated positively with CMR-derived RV end-diastolic volume and negatively with echocardiography-derived LV and RV EF (all p < 0.05). Multiple linear regression identified sex and RV EF as significant correlates of log-transformed hs-cTnT levels. Increased hs-cTnT levels occur in 30% of female patients after TOF repair, and are associated with greater RV volumes and worse RV EF. PMID:26360613

Time to shift from contemporary to high-sensitivity cardiac troponin in diagnosis of acute coronary syndromes

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Jamshed J. Dalal

2016-11-01

Training and displaying the clinical algorithm depicting the role of hs-TnI assay in acute cardiac care units and in EDs are an efficient way to deliver the new standard of care to patients. Compared with contemporary troponin assays, the hs-cTn assay accelerates the diagnostic pathway to 0–1 h, thus reducing the time for diagnosis of NSTEMI and hence, its management.

Prognostic prediction of troponins in cardiac myxoma: case study with literature review

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Shi-Min Yuan

2015-04-01

Full Text Available AbstractObjective:It was supposed that troponins in cardiac myxoma patients might be in a same fashion as in the conditions without myocardial injury. In order to verify this hypothesis, troponins in cardiac myxoma patients were discussed by presenting a comprehensive retrieval of the literature with incorporating the information of a recent patient.Methods:Postoperative detections of troponin I, creatine kinase isoenzyme MB (CK-MB and N-terminal pro-B-type natriuretic peptide revealed elevated troponin I and CK-MB and normal N-terminal pro-B-type natriuretic peptide. Postoperative troponin I and CK-MB shared a same trend, reaching a peak value at postoperative hour 2, gradually decreased on postoperative day 1, and reached a plateau on postoperative days 7 and 13. A significant correlation could be noted between the postoperative values of the two indicators (Y=0.0714X + 0.6425, r2=0.9111, r=0.9545, P=0.0116. No significant linear correlation between troponin I and N-terminal pro-B-type natriuretic peptide were found. Literature review of troponins in cardiac myxoma patients revealed the uncomplicated patients had a normal or only slightly elevated troponin before open heart surgery. However, the complicated patients (with cerebral or cardiac events showed a normal preoperative troponin in 3 (23.1% and an elevated troponin in 10 (76.9% patients (χ2=7.54, P=0.0169, Fisher's exact test. The overall quantitative result of troponin I was 2.45±2.53 µg/L, and that of troponin T was 3.10±4.29 mg/L, respectively.Conclusion:Troponins are not necessarily elevated in patients with a cardiac myxoma without coronary syndrome. By contrast, patients with a cardiac myxoma with an elevated troponin may herald the presence of an associated coronary event. An old cerebral infarct does not necessarily cause an elevation of troponin or B-type natriuretic peptide, or new neurological events, but might lead to a delayed awakening.

Relationship between Cardiac Troponin and Thrombo-Inflammatory Molecules in Prediction of Outcome after Acute Ischemic Stroke

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Csecsei, Peter; Pusch, Gabriella; Ezer, Erzsebet

2018-01-01

BACKGROUND: In patients with acute ischemic stroke (AIS) without cardiovascular complications, we investigated the association of serum concentration of cardiac troponin (high-sensitivity cardiac troponin T [hs-cTnT]) with thrombo-inflammatory markers. METHODS: Thirty-five patients with first......-ever AIS were prospectively examined. Serum hs-cTnT was measured 6 and 24 hours after stroke, whereas S100B, high-sensitivity C-reactive protein (hsCRP), soluble CD40 ligand, tissue plasminogen activator (tPA), monocyte chemoattractant protein-1 (MCP-1), and P-selectin were measured 6 and 72 hours after...... stroke. Severity of stroke was assessed by the National Institutes of Health Stroke Scale (NIHSS) on admission, 24 hours later, and at discharge. RESULTS: Concentration of MCP-1 at 6 hours was higher in the serum of patients with worsened NIHSS by 24 hours (P = .009). Concentration of hs-cTnT at both 6...

Increase in Cardiac Troponin I in a Lamb with Tetralogy of Fallot

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NEUWALD, Elisa Barp; SOARES, Frederico Aécio Carvalho; DREYER, Cristina Terres; CARNESELLA, Samuel; WOUTERS, Angelica Terezinha Barth; GONZÁLEZ, Félix Hilario Diaz; DRIEMEIER, David

2013-01-01

ABSTRACT This study describes a case of tetralogy of Fallot in a lamb showing failure to thrive and signs of respiratory distress. Physical examination, electrocardiography, thoracic radiographies, echocardiography and cardiac troponin I evaluation were performed. The value of cardiac troponin I was compared with the values of 10 healthy lambs of the same age and breed, and the affected animal demonstrated an increase in cardiac troponin I. Due to the poor prognosis, euthanasia was indicated, and necropsy confirmed the diagnosis. This is the first report of an increase in cardiac troponin I in a lamb with tetralogy of Fallot. PMID:23685750

Upconverting nanophosphors as reporters in a highly sensitive heterogeneous immunoassay for cardiac troponin I

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Sirkka, Nina, E-mail: nkelon@utu.fi; Lyytikäinen, Annika; Savukoski, Tanja; Soukka, Tero

2016-06-21

Photon upconverting nanophosphors (UCNPs) have a unique capability to produce anti-Stokes emission at visible wavelengths via sequential multiphoton absorption upon infrared excitation. Since the anti-Stokes emission can be easily spectrally resolved from the Stokes' shifted autofluorescence, the upconversion luminescence (UCL) is a highly attractive reporter technology for optical biosensors and biomolecular binding assays – potentially enabling unprecedented sensitivity in separation-based solid-phase immunoassays. UCL technology has not previously been applied in sensitive detection of cardiac troponin I (cTnI), which requires highly sensitive detection to enable accurate and timely diagnosis of myocardial infarction. We have developed an UCL-based immunoassay for cTnI using NaYF{sub 4}: Yb{sup 3+}, Er{sup 3+} UCNPs as reporters. Biotinylated anti-cTnI monoclonal antibody (Mab) and Fab fragment immobilized to streptavidin-coated wells were used to capture cTnI. Captured cTnI was detected from dry well surface after a 15 min incubation with poly(acrylic acid) coated UCNPs conjugated to second anti-cTnI Mab. UCL was measured with a dedicated UCL microplate reader. The UCL-based immunoassay allowed sensitive detection of cTnI. The limit of detection was 3.14 ng L{sup −1}. The calibration curve was linear up to cTnI concentration 50,000 ng L{sup −1}. Plasma recoveries of added cTnI were 92–117%. Obtained cTnI concentrations from five normal plasma samples were 4.13–10.7 ng L{sup −1} (median 5.06 ng L{sup −1}). There is yet significant potential for even further improved limit of detection by reducing non-specifically bound fraction of the Mab-conjugated UCNPs. The assay background with zero calibrator was over 40-fold compared to the background obtained from wells where the reporter conjugate had been excluded. - Highlights: • Detection of attomole analyte quantity in microwell using upconversion luminescence. • Upconverting

Prospective study of cardiac troponin I release in patients with upper gastrointestinal bleeding.

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Iser, David M; Thompson, Alexander J V; Sia, Koon Ket; Yeomans, Neville D; Chen, Robert Y M

2008-06-01

The rate of cardiac injury in upper gastrointestinal hemorrhage is unclear. The aims of this study were to determine prospectively the risk of cardiac troponin I release and associated adverse cardiac events in patients with acute upper gastrointestinal hemorrhage. From January to September 2003, we prospectively studied patients with documented hematemesis and melena referred to the gastroenterology unit in a tertiary teaching hospital in Melbourne, Australia. Serial assays for cardiac troponin I were performed at 0, 12 and 24 h. Serial creatine kinase levels and electrocardiographs were also performed. Clinical and biochemical data were collected. The primary endpoint was a troponin level >0.5 microg/L within 24 h of recruitment. Various clinical variables were then compared between the groups of patients with or without troponin rise. A total of 156 patients were included in the study. The mean age was 67 years (range 19-96). There were 104 (67%) male patients. A troponin level of greater than 0.5 microg/L was found in 30/156 (19%); 126 (81%) patients had normal troponin levels. Age greater than 65 years, signs of hemodynamic instability at presentation, a recent history of cardiac disease, cardiovascular compromise following endoscopy, and re-bleeding were associated with troponin release. Upper gastrointestinal bleeding is associated with a risk of cardiac injury of up to 19%. Troponin assay could be used to screen for cardiac damage, especially in elderly patients who present with hemodynamic instability.

Validation of an accelerated high-sensitivity troponin T assay protocol in an Australian cohort with chest pain.

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Parsonage, William A; Greenslade, Jaimi H; Hammett, Christopher J; Lamanna, Arvin; Tate, Jillian R; Ungerer, Jacobus P; Chu, Kevin; Than, Martin; Brown, Anthony F T; Cullen, Louise

2014-02-17

To validate an accelerated biomarker strategy using a high-sensitivity cardiac troponin T (hs-cTnT) assay for diagnosing acute myocardial infarction (AMI) in patients presenting to the emergency department with chest pain; and to validate this strategy in combination with the National Heart Foundation of Australia/Cardiac Society of Australia and New Zealand risk stratification model. Single-centre, prospective, observational cohort study of 764 adults presenting to a tertiary hospital with symptoms of possible acute coronary syndrome between November 2008 and February 2011. AMI or cardiac death within 24 hours of presentation (primary), and major adverse cardiac events within 30 days (secondary). An elevated hs-cTnT assay result above the 99th percentile at either the 0 h or 2 h time points had sensitivity of 96.4% (95% CI, 87.9%-99.0%), specificity of 82.6% (95% CI, 79.7%-85.2%), negative predictive value of 99.7% (95% CI, 98.8%-99.9%) and positive predictive value of 30.5% (95% CI, 24.2%-37.6%) for diagnosing AMI. Compared with a traditional 6 h cardiac troponin testing strategy, the accelerated strategy led to reclassification of risk in only two patients with adverse cardiac outcomes, with no net effect on appropriate management. In patients presenting with chest pain, an accelerated biomarker strategy using the hs-cTnT assay performed well in the initial diagnosis of AMI. The accelerated strategy was also effective when incorporated into a comprehensive strategy of risk stratification that included clinical and demographic factors. The time saved by this approach could have a major impact on health service delivery. Australian New Zealand Clinical Trials Registry ACTRN12610000053022.

Diagnostic value of exercise-induced changes in circulating high sensitive troponin T in stable chest pain patients

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Mouridsen, Mette Rauhe; Nielsen, Olav Wendelboe; Pedersen, Ole Dyg

2013-01-01

We investigated the diagnostic value of exercise-induced increase in cardiac Troponin T (cTnT) in stable chest pain subjects.......We investigated the diagnostic value of exercise-induced increase in cardiac Troponin T (cTnT) in stable chest pain subjects....

High sensitivity troponin and valvular heart disease.

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McCarthy, Cian P; Donnellan, Eoin; Phelan, Dermot; Griffin, Brian P; Enriquez-Sarano, Maurice; McEvoy, John W

2017-07-01

Blood-based biomarkers have been extensively studied in a range of cardiovascular diseases and have established utility in routine clinical care, most notably in the diagnosis of acute coronary syndrome (e.g., troponin) and the management of heart failure (e.g., brain-natriuretic peptide). The role of biomarkers is less well established in the management of valvular heart disease (VHD), in which the optimal timing of surgical intervention is often challenging. One promising biomarker that has been the subject of a number of recent VHD research studies is high sensitivity troponin (hs-cTn). Novel high-sensitivity assays can detect subclinical myocardial damage in asymptomatic individuals. Thus, hs-cTn may have utility in the assessment of asymptomatic patients with severe VHD who do not have a clear traditional indication for surgical intervention. In this state-of-the-art review, we examine the current evidence for hs-cTn as a potential biomarker in the most commonly encountered VHD conditions, aortic stenosis and mitral regurgitation. This review provides a synopsis of early evidence indicating that hs-cTn has promise as a biomarker in VHD. However, the impact of its measurement on clinical practice and VHD outcomes needs to be further assessed in prospective studies before routine clinical use becomes a reality. Copyright © 2017 Elsevier Inc. All rights reserved.

Combined determination of highly sensitive troponin T and copeptin for early exclusion of acute myocardial infarction: first experience in an emergency department of a general hospital

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Lotze U

2011-08-01

Full Text Available Ulrich Lotze1, Holger Lemm2, Anke Heyer2, Karin Müller31Department of Internal Medicine, German Red Cross Hospital Sondershausen, Sondershausen, 2Department of Internal Medicine, 3Department of Laboratory Medicine, Saale-Unstrut Hospital Naumburg, Naumburg, GermanyBackground: The purpose of this observational study was to test the diagnostic performance of the Elecsys® troponin T high-sensitive system combined with copeptin measurement for early exclusion of acute myocardial infarction (MI in clinical practice.Methods: Troponin T high-sensitive (diagnostic cutoff: <14 pg/mL and copeptin (diagnostic cutoff: <14 pmol/L levels were determined at admission in addition to other routine laboratory parameters in patients with suspected acute MI presenting to the emergency department of a general hospital over a period of five months.Results: Data from 142 consecutive patients (mean age 71.2 ± 13.5 years, 76 men were analyzed. Final diagnoses were acute MI in 13 patients (nine ST elevation MI, four non-ST elevation MI, 9.2% unstable angina pectoris in three (2.1%, cardiac symptoms not primarily associated with myocardial ischemia in 79 (55.6%, and noncardiac disease in 47 patients (33.1%. The patients with acute MI were younger and had higher troponin T high-sensitive and copeptin values than patients without acute MI. Seventeen patients had very high copeptin values (>150 pmol/L, one of whom had a level of >700 pmol/L and died of pulmonary embolism. A troponin T high-sensitive level of <14 pg/mL in combination with copeptin <14 pmol/L at initial presentation ruled out acute MI in 45 of the 142 patients (31.7%, each with a sensitivity and negative predictive value of 100%.Conclusion: According to this early experience, a single determination of troponin T high-sensitive and copeptin may enable early and accurate exclusion of acute MI in one third of patients, even in an emergency department of a general hospital.Keywords: highly sensitive troponin T

Cardiac troponin I (CTnI level among children with epileptic seizures

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Ahmed Anwer Attia Khattab

2014-09-01

Conclusion: Cardiac troponin I is a perfect tool for early detection of cases with myocardial dysfunction in epileptic patients – cardiac troponin I is significantly increased in children with epilepsy especially the complicated epilepsy. Cardiac injury in epileptic children is more common in patients with early onset epilepsy, positive prenatal problem, idiopathic epilepsy, abnormal imaging and EEG – elevated TnI levels may be of value in assessing the severity and eventual outcome and mortality risk of the disease in children with epilepsy.

Combining High Sensitivity Cardiac Troponin I and Cardiac Troponin T in the Early Diagnosis of Acute Myocardial Infarction.

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van der Linden, Noreen; Wildi, Karin; Twerenbold, Raphael; Pickering, John W; Than, Martin; Cullen, Louise; Greenslade, Jaimi; Parsonage, William; Nestelberger, Thomas; Boeddinghaus, Jasper; Badertscher, Patrick; Rubini Giménez, Maria; Klinkenberg, Lieke J J; Bekers, Otto; Schöni, Aline; Keller, Dagmar I; Sabti, Zaid; Puelacher, Christian; Cupa, Janosch; Schumacher, Lukas; Kozhuharov, Nikola; Grimm, Karin; Shrestha, Samyut; Flores, Dayana; Freese, Michael; Stelzig, Claudia; Strebel, Ivo; Miró, Òscar; Rentsch, Katharina; Morawiec, Beata; Kawecki, Damian; Kloos, Wanda; Lohrmann, Jens; Richards, A Mark; Troughton, Richard; Pemberton, Christopher; Osswald, Stefan; van Dieijen-Visser, Marja P; Mingels, Alma M; Reichlin, Tobias; Meex, Steven J R; Mueller, Christian

2018-04-24

Background -Combining two signals of cardiomyocyte injury, cardiac troponin I (cTnI) and T (cTnT), might overcome some individual pathophysiological and analytical limitations and thereby increase diagnostic accuracy for acute myocardial infarction (AMI) with a single blood draw. We aimed to evaluate the diagnostic performance of combinations of high sensitivity (hs) cTnI and hs-cTnT for the early diagnosis of AMI. Methods -The diagnostic performance of combining hs-cTnI (Architect, Abbott) and hs-cTnT (Elecsys, Roche) concentrations (sum, product, ratio and a combination algorithm) obtained at the time of presentation was evaluated in a large multicenter diagnostic study of patients with suspected AMI. The optimal rule out and rule in thresholds were externally validated in a second large multicenter diagnostic study. The proportion of patients eligible for early rule out was compared with the ESC 0/1 and 0/3 hour algorithms. Results -Combining hs-cTnI and hs-cTnT concentrations did not consistently increase overall diagnostic accuracy as compared with the individual isoforms. However, the combination improved the proportion of patients meeting criteria for very early rule-out. With the ESC 2015 guideline recommended algorithms and cut-offs, the proportion meeting rule out criteria after the baseline blood sampling was limited (6-24%) and assay dependent. Application of optimized cut-off values using the sum (9 ng/L) and product (18 ng2/L2) of hs-cTnI and hs-cTnT concentrations led to an increase in the proportion ruled-out after a single blood draw to 34-41% in the original (sum: negative predictive value (NPV) 100% (95%CI: 99.5-100%); product: NPV 100% (95%CI: 99.5-100%) and in the validation cohort (sum: NPV 99.6% (95%CI: 99.0-99.9%); product: NPV 99.4% (95%CI: 98.8-99.8%). The use of a combination algorithm (hs-cTnI <4 ng/L and hs-cTnT <9 ng/L) showed comparable results for rule out (40-43% ruled out; NPV original cohort 99.9% (95%CI: 99.2-100%); NPV

Pim-1 Kinase Phosphorylates Cardiac Troponin I and Regulates Cardiac Myofilament Function

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Ni Zhu

2018-03-01

Full Text Available Background/Aims: Pim-1 is a serine/threonine kinase that is highly expressed in the heart, and exerts potent cardiac protective effects through enhancing survival, proliferation, and regeneration of cardiomyocytes. Its myocardial specific substrates, however, remain unknown. In the present study, we aim to investigate whether Pim-1 modulates myofilament activity through phosphorylation of cardiac troponin I (cTnI, a key component in regulating myofilament function in the heart. Methods: Coimmunoprecipitation and immunofluorescent assays were employed to investigate the interaction of Pim-1 with cTnI in cardiomyocytes. Biochemical, site directed mutagenesis, and mass spectrometric analyses were utilized to identify the phosphorylation sites of Pim1 in cTnI. Myofilament functional assay using skinned cardiac fiber was used to assess the effect of Pim1-mediated phosphorylation on cardiac myofilament activity. Lastly, the functional significance of Pim1-mediated cTnI in heart disease was determined in diabetic mice. Results: We found that Pim-1 specifically interacts with cTnI in cardiomyocytes and this interaction leads to Pim1-mediated cTnI phosphorylation, predominantly at Ser23/24 and Ser150. Furthermore, our functional assay demonstrated that Pim-1 induces a robust phosphorylation of cTnI within the troponin complex, thus leading to a decreased Ca2+ sensitivity. Insulin-like growth factor 1 (IGF-1, a peptide growth factor that has been shown to stimulate myocardial contractility, markedly induces cTnI phosphorylation at Ser23/24 and Ser150 through increasing Pim-1 expression in cardiomyocytes. In a high-fat diabetic mice model, the expression of Pim1 in the heart is significantly decreased, which is accompanied by a decreased phosphorylation of cTnI at Ser23/24 and Ser150, further implicating the pathological significance of the Pim1/cTnI axis in the development of diabetic cardiomyopathy. Conclusion: Our results demonstrate that Pim-1 is a

Predictive value of routine point-of-care cardiac troponin T measurement for prehospital diagnosis and risk-stratification in patients with suspected acute myocardial infarction

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Rasmussen, Martin B; Stengaard, Carsten; Sørensen, Jacob T

2017-01-01

-of-care cardiac troponin T measurements (11.0%) had a value ≥50 ng/l, including 966 with acute myocardial infarction (sensitivity: 44.2%, specificity: 92.8%). Patients presenting with a prehospital point-of-care cardiac troponin T value ≥50 ng/l had a one-year mortality of 24% compared with 4.8% in those...... with values analysis: point-of-care cardiac troponin T≥50 ng/l (hazard ratio 2.10, 95% confidence interval: 1.90-2.33), congestive heart failure (hazard ratio 1.93, 95% confidence interval: 1......OBJECTIVE: The purpose of this study was to determine the predictive value of routine prehospital point-of-care cardiac troponin T measurement for diagnosis and risk stratification of patients with suspected acute myocardial infarction. METHODS AND RESULTS: All prehospital emergency medical service...

Establishment of colloid gold immunity chromatography assay for cardiac troponin I (cTnI)

International Nuclear Information System (INIS)

Wang Dezhi; Chen Jiying; Qin Lili; Zhao Baojian; Zhang Chunming

2006-01-01

Objective: To establish the colloid gold Immunity chromatography assay for cardiac troponin I. Methods: To purify cTnI from human cardiac muscle and immunize rabbit with it. cTnI antibody of rabbit anti-human cardiac muscle has been prepared and colloid gold immunity chromatography assay was established by using immunity chromatography technology. Results: Anti-serum titles of cTnI were 1:100000, Ka=2.38 x 10 9 L/mol; Methodological index: Sensitivity: 5 ng/ml; Specificity: cTnI is no cross-reaction with cTnT, cTnC and CK-MB. conclusion: The assay is highly specific, quick and simple. It can be widely used for the early diagnosis of AMI and scientific research. (authors)

Immediate rule-out of acute myocardial infarction using electrocardiogram and baseline high-sensitivity troponin I

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Neumann, Johannes Tobias; Sörensen, Nils Arne; Ojeda, Francisco

2017-01-01

AIMS: Serial measurements of high-sensitivity troponin are used to rule out acute myocardial infarction (AMI) with an assay specific cutoff at the 99th percentile. Here, we evaluated the performance of a single admission troponin with a lower cutoff combined with a low risk electrocardiogram (ECG...

Continuous cardiac troponin I release in Fabry disease.

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Feustel, Andreas; Hahn, Andreas; Schneider, Christian; Sieweke, Nicole; Franzen, Wolfgang; Gündüz, Dursun; Rolfs, Arndt; Tanislav, Christian

2014-01-01

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. 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). Three patients (21%) without specific vascular risk factors other than FD had persistent cTNI-elevations (range 0.05-0.71 ng/ml, normal: 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. 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.

Cardiospecific troponins in non-ischemic cardiological pathologies

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Giuseppe Lippi

2006-10-01

Full Text Available Cardiospecific troponin T (TnT and I (TnI are low-molecularweight proteins that form part of the troponin complex and are integral components of the myofibrillar contractile apparatus of the heart. Loss of integrity of cardiac myocyte membranes causes release of cardiac troponins into the circulation, which can be detected by highly sensitive assays for cTnT and cTnI developed to the stat diagnosis of acute coronary syndrome. Regardless of preanalytical and analytical sources (incorrect collection or handling of the specimen, malfunctioning of the analyzer, heterophilic antibodies, a diagnostic troponin value is expression of myocardial damage, though it does not provide definitive clue on the nature of such an increment. In fact, increases in serum cardiac troponins also occur in the absence of cardiac ischemia and may sometimes led to an inappropriate or unjustified clinical decision making. Abnormal troponin values in plasma are frequently observed in various clinical contexts independent from the acute coronary disease, like myocarditis, pulmonary embolism, acute heart failure, septic shock, and as a result of cardiotoxic drugs as well as after therapeutic procedures like coronary angioplasty, electrophysiological ablations, or electrical cardioversion. Awareness of this issue is essential to either prevent unjustified alarmism or underestimation of clinical situations that may finally compromise the patient’s health.

Head-to-head comparison of cardiac troponin T and troponin I in patients without acute coronary syndrome

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Árnadóttir, Ásthildur; Falk Klein, Christine; Iversen, Kasper

2017-01-01

BACKGROUND: Cardiac-specific troponin T (cTnT) and troponin I (cTnI) are considered diagnostically equal in patients with acute coronary syndrome (ACS). The aim of this systematic review was to compare the prevalence and prognostic strength of elevations of cTnT and cTnI in patients with other...

Serial Sampling of High-Sensitivity Cardiac Troponin T May Not Be Required for Prediction of Acute Myocardial Infarction Diagnosis in Chest Pain Patients with Highly Abnormal Concentrations at Presentation.

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Mueller-Hennessen, Matthias; Mueller, Christian; Giannitsis, Evangelos; Biener, Moritz; Vafaie, Mehrshad; deFilippi, Christopher R; Christ, Michael; Ordóñez-Llanos, Jorge; Panteghini, Mauro; Plebani, Mario; Verschuren, Franck; Melki, Dina; French, John K; Christenson, Robert H; Body, Richard; McCord, James; Dinkel, Carina; Katus, Hugo A; Lindahl, Bertil

2017-02-01

Guidelines for diagnosing acute myocardial infarction (AMI) recommend adding kinetic changes to the initial cardiac troponin (cTn) blood concentration to improve AMI diagnosis. We hypothesized that kinetic changes may not be required in patients presenting with highly abnormal cTn. Patients presenting with suspected AMI to the emergency department were enrolled in a prospective diagnostic study. We assessed the positive predictive value (PPV) of initial high-sensitivity cardiac troponin T (hs-cTnT) blood concentrations alone and in combination with kinetic changes for AMI. Predefined relative changes (δ change of ≥20%) and absolute changes (Δ change ≥9.2 ng/L) within different time intervals (1 h, 2 h, and 4-14 h after presentation) were assessed. The final diagnosis was adjudicated by 2 independent cardiologists. Among 1282 patients, 213 (16.6%) patients had a final diagnosis of AMI. For AMI prediction, PPVs increased from 48.8% for an initial hs-cTnT >14 ng/L to 87.2% for >60 ng/L, whereas PPVs remained unchanged for higher hs-cTnT concentrations at baseline (87.1% for both >80 ng/L and >100 ng/L). With addition of 20% relative Δ change, PPVs were not further improved in patients with baseline hs-cTnT >80 ng/L using the 1-h (84.0%) and 2-h (88.9%) intervals, and only minimally when extending the interval to 4-14 h (91.2% for >80 ng/L and 90.4% for >100 ng/L, respectively). Similar findings were observed when applying absolute changes. In chest pain patients with highly abnormal hs-cTnT concentrations at presentation, subsequent blood draws may not be required, as they do not provide incremental diagnostic value for prediction of AMI diagnosis. © 2016 American Association for Clinical Chemistry.

High-sensitivity troponin assays for the early rule-out or diagnosis of acute myocardial infarction in people eith acute chest pain: a systematic review and cost-effectiveness analysis

NARCIS (Netherlands)

M. Westwood (Marie); T. van Asselt (Thea); B. Ramaekers (Bram); P. Whiting (Penny); P. Tokala (Praveen); M.A. Joore (Manuela); N. Armstrong (Nigel); J. Ross (Janine); J.L. Severens (Hans); J. Kleijnen (Jos)

2015-01-01

textabstractBackground: Early diagnosis of acute myocardial infarction (AMI) can ensure quick and effective treatment but only 20% of adults with emergency admissions for chest pain have an AMI. High-sensitivity cardiac troponin (hs-cTn) assays may allow rapid rule-out of AMI and avoidance of

High-sensitivity troponin assays for the early rule-out or diagnosis of acute myocardial infarction in people with acute chest pain : a systematic review and cost-effectiveness analysis

NARCIS (Netherlands)

Westwood, Marie; van Asselt, Thea; Ramaekers, Bram; Whiting, Penny; Thokala, Praveen; Joore, Manuela; Armstrong, Nigel; Ross, Janine; Severens, Johan; Kleijnen, Jos

BACKGROUND: Early diagnosis of acute myocardial infarction (AMI) can ensure quick and effective treatment but only 20% of adults with emergency admissions for chest pain have an AMI. High-sensitivity cardiac troponin (hs-cTn) assays may allow rapid rule-out of AMI and avoidance of unnecessary

A carbon nanotube screen-printed electrode for label-free detection of the human cardiac troponin T.

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Silva, Bárbara V M; Cavalcanti, Igor T; Silva, Mízia M S; Dutra, Rosa F

2013-12-15

Label-free immunosensor based on amine-functionalized carbon nanotubes screen-printed electrode is described for detection of the cardiac troponin T, an important marker of acute myocardial infarction. The disposable sensor was fabricated by tightly squeezing an adhesive carbon ink containing carbon nanotubes onto a polyethylene terephthalate substrate forming a thin film. The use of carbon nanotubes increased the reproducibility and stability of the sensor, and the amine groups permitted nonrandom immobilization of antibodies against cardiac troponin T. Amperometric responses were obtained by differential pulse voltammetry in presence of a ferrocyanide/ferricyanide redox probe after troponin T incubation. The calibration curve indicated a linear response of troponin T between 0.0025 ng mL(-1) and 0.5 ng mL(-1), with a good correlation coefficient (r=0.995; p<0.0001, n=7). The limit of detection (0.0035 ng mL(-1) cardiac troponin T) was lower than any previously described by immunosensors and was comparable with conventional analytical methods. The high reproducibility and clinical range obtained using this immunosensor support its utility as a potential tool for point-of-care acute myocardial infarction diagnostic testing. © 2013 Elsevier B.V. All rights reserved.

Cardiac Troponin I, Creatine Phosphokinase and Myoglobine Levels in Preeclampsia

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Ahmet Kale

2005-01-01

Full Text Available To evaluate minor myocardial injury in preeclamptic pregnancies by serum markers of cardiac troponin-I, creatine phosphokinase and myoglobine. Group I consisted of 45 preeclamptic pregnancies, Group 2 consisted of uncomplicated pregnancies. The groups were compared for maternal age, parity, mean troponin–I, creatine phosphokinase and myoglobine values. Student-t test were used in statistical analyses. Significance was accepted as p<0.05. Cardiac troponin-I levels were statistically significantly higher in preeclamptic pregnancies (0,97 ± 0,11ng/ml than control groups (0,12 ± 0.09 ng/ml (p<0.001. No statistically significant difference was found with mean levels of creatine phosphokinase and myoglobin levels between two groups. Higher values of troponin-I’in preeclamptic patients is thought to be a result of myocardial injury and associated with pregnancy-induced hypertension.

Continuous cardiac troponin I release in Fabry disease.

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Andreas Feustel

Full Text Available 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.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.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.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.

Effectiveness of 2-hour Troponin in High-risk Patients With Suspected Acute Coronary Syndrome.

Science.gov (United States)

Bove, Joseph; Hochman, Steven; Miller, Jacob; Artim, Stephen

2017-06-01

Research has shown the safety and effectiveness of drawing a standard troponin level at presentation and again at 2 hours in only low-risk patients. Because high-sensitivity troponins are not currently approved in the United States, we studied the utility of a standard troponin that is presently in use. Our goal was to determine if 2-hour standard troponin would be safe and effective in the evaluation of a high-risk cohort of patients never studied previously. We conducted a single-center prospective observational study of adult patients presenting to the emergency department with signs and symptoms suggestive of acute coronary syndrome. Patients were defined as high risk if the attending physician planned to admit or transfer the patient to the observation unit. History, Electrocardiography, Age, Risk factors, Troponin scores were calculated on all patients to provide verification that the individuals were high risk. The primary outcome was a composite of 30-day myocardial infarction, death, cardiac arrest with return of spontaneous circulation, or dysrhythmia. The secondary outcome was 30-day revascularization. We included a total of 122 patients with an average follow-up of 112 days (minimum 30 days). A total of 86% of cases had History, Electrocardiography, Age, Risk factors, Troponin scores ≥4. The primary outcome was met in 22 (18%) patients, and the secondary outcome occurred in 7 (5.7%) patients. The negative predictive value of negative 2-hour troponins along with no significant delta troponin rise was 98.7%. Discharging patients thought to be high risk who have negative troponins at 0 and 2 hours and no delta troponin rise appears safe. No deaths occurred in follow-up. Larger studies are warranted.

Absolute and relative kinetic changes of high-sensitivity cardiac troponin T in acute coronary syndrome and in patients with increased troponin in the absence of acute coronary syndrome.

Science.gov (United States)

Mueller, Matthias; Biener, Moritz; Vafaie, Mehrshad; Doerr, Susanne; Keller, Till; Blankenberg, Stefan; Katus, Hugo A; Giannitsis, Evangelos

2012-01-01

We evaluated kinetic changes of high-sensitivity cardiac troponin T (hs-cTnT) in patients with acute coronary syndrome (ACS) and patients with hs-cTnT increases not due to ACS to rule in or rule out non-ST-segment elevation myocardial infarction (STEMI). hs-cTnT was measured serially in consecutive patients presenting to the emergency department. Patients with ACS who had at least 2 hs-cTnT measurements within 6 h and non-ACS patients with hs-cTnT concentrations above the 99th percentile value (14 ng/L) were enrolled to compare absolute and relative kinetic changes of hs-cTnT. For discrimination of non-STEMI (n=165) in the entire study population (n=784), the absolute δ change with the ROC-optimized value of 9.2 ng/L yielded an area under the curve of 0.898 and was superior to all relative δ changes (Prise or fall of at least 9.2 ng/L in the entire study population and 6.9 ng/L in selected ACS patients seems adequate to rule-out non-STEMI. However, δ-values are useful to rule-in non-STEMI only in a specific ACS population.

The ZnO-FET Biosensor for Cardiac Troponin I

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Fathil, M. F. M.; Arshad, M. K. Md; Nuzaihan, M. N. M.; Gopinath, Subash C. B.; Ruslinda, A. R.; Hashim, U.

2018-03-01

This paper investigates the influence of substrate-gate coupling on the ZnO-FET biosensor’s sensitivity for detection of cardiac troponin I (cTnI), a ‘gold standard’ biomarker for acute myocardial infarction (AMI). The FET-based device with introduction of substrate-gate coupling on p-type silicon-on-insulator (SOI) substrate is fabricated using conventional lithography processes. An n-type zinc oxide (ZnO) thin film deposited via electron-beam evaporator is used as transducer for bridging the source and drain regions. Surface modifications via functionalization with 3-aminopropyltriethoxysilane (APTES) and glutaraldehyde (GA) as chemical linkers, followed by immobilization of cTnI monoclonal antibody (MAb-cTnI) as bio-receptor on the ZnO thin film allow different concentration of cTnI detection with high selectivity. The device’s sensitivity increases up to 9 %·(g/ml)-1 with the increase of the substrate-gate voltage (VSG) up to -10 V at very low limit of detection (LOD) down to 1.6 fg/ml.

Drug-Induced Rhabdomyolysis with Elevated Cardiac Troponin T

DEFF Research Database (Denmark)

Egholm, Gro; Pareek, Manan

2015-01-01

for myocardial injury. This case report describes a 48-year-old woman, who, two years after cardiac transplantation, presented with rhabdomyolysis. During the course of the disease, her troponin T level was elevated on repeated occasions, but other definitive evidence of myocardial injury was not found...

European multicenter analytical evaluation of the Abbott ARCHITECT STAT high sensitive troponin I immunoassay

DEFF Research Database (Denmark)

Krintus, Magdalena; Kozinski, Marek; Boudry, Pascal

2014-01-01

BACKGROUND: International recommendations highlight the superior value of cardiac troponins (cTns) for early diagnosis of myocardial infarction along with analytical requirements of improved precision and detectability. In this multicenter study, we investigated the analytical performance of a ne...

Epicardial fat thickness in stable coronary artery disease: its relationship with high-sensitive cardiac troponin T and N-terminal pro-brain natriuretic peptide.

Science.gov (United States)

Börekçi, Abdurrezzak; Gür, Mustafa; Özaltun, Betül; Baykan, Ahmet Oytun; Harbalioğlu, Hazar; Seker, Taner; Sen, Ömer; Acele, Armağan; Gözükara, Mehmet Yavuz; Kuloğlu, Osman; Koç, Mevlüt; Çayli, Murat

2014-12-01

Epicardial adipose tissue is related to coronary atherosclerosis, left ventricle hypertrophy, myocardial dysfunction, cardiomyopathy, and inflammation, which produces a variety of cytokines that influence key pathogenic mechanisms of atherogenesis. The main goal of this study is to examine the relationship between epicardial fat thickness (EFT) and cardiovascular risk markers as well as the complexity of coronary artery disease (CAD) in patients with stable CAD. We prospectively included 439 stable CAD patients undergoing coronary angiography in the present study (mean age: 62.2±10.7 years). Patients were divided into two groups (EFTlow and EFThigh groups) according to their median EFT values. EFT was evaluated by two-dimensional echocardiography before angiography. The SYNTAX score was calculated in all patients. N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitive C-reactive protein (hs-CRP), high-sensitive cardiac troponin T (hs-cTnT), uric acid, and other biochemical markers were also measured. Age, SYNTAX score, frequencies of diabetes, hyperlipidemia, and hypertension, NT-proBNP, hs-CRP, hs-cTnT, and uric acid levels were higher in EFThigh group compared with the EFTlow group (P<0.05 for all). EFT was associated independently with age (β=-0.102, P=0.001), diabetes (β=-0.083, P=0.011), SYNTAX score (β=0.352, P<0.001), hs-CRP level (β=0.217, P<0.001), hs-cTnT level (β=0.197, P<0.001), and NT-proBNP level (β=0.300, P<0.001) in multivariate analysis. EFT obtained by echocardiograpy may not only be an easy tool but also an important tool for early detection of increased cardiac risk as well as the extent and complexity of CAD in patients with stable CAD.

Peptide Functionalized Gold Nanorods for the Sensitive Detection of a Cardiac Biomarker Using Plasmonic Paper Devices (Postprint)

Science.gov (United States)

2015-11-10

Albumin to saturate the non-specific binding sites on the paper substrate prior to troponin exposure. For testing the biosensor, troponin of various...AFRL-RX-WP-JA-2016-0191 PEPTIDE FUNCTIONALIZED GOLD NANORODS FOR THE SENSITIVE DETECTION OF A CARDIAC BIOMARKER USING PLASMONIC PAPER ...SENSITIVE DETECTION OF A CARDIAC BIOMARKER USING PLASMONIC PAPER DEVICES (POSTPRINT) 5a. CONTRACT NUMBER FA8650-15-D-5405-0001 5b. GRANT NUMBER 5c

Diagnosis of unstable angina pectoris has declined markedly with the advent of more sensitive troponin assays.

Science.gov (United States)

D'Souza, Maria; Sarkisian, Laura; Saaby, Lotte; Poulsen, Tina S; Gerke, Oke; Larsen, Torben B; Diederichsen, Axel C P; Jangaard, Nikolaj; Diederichsen, Søren Z; Hosbond, Susanne; Hove, Jens; Thygesen, Kristian; Mickley, Hans

2015-08-01

Since the arrival of the universal definition of myocardial infarction more sensitive troponin assays have been developed. How these occurrences have influenced the proportions and clinical features of the components of acute coronary syndrome have not been studied prospectively in unselected hospital patients. During 2010 we evaluated all patients in whom cardiac troponin I had been measured at a single university hospital. The diagnosis of acute myocardial infarction (ST-elevation myocardial infarction [STEMI] or non-ST-elevation myocardial infarction [NSTEMI]) was established in cases of a rise and/or fall of cardiac troponin I together with cardiac ischemic features. Patients with unstable chest discomfort and cardiac troponin I values below the decision limit of myocardial infarction were diagnosed as having unstable angina pectoris. The definition of acute coronary syndrome included unstable angina pectoris, NSTEMI, and STEMI. Mortality data were obtained from the Danish Civil Personal Registration System. Of 3762 consecutive patients, 516 had acute coronary syndrome. Unstable angina pectoris was present in 7%, NSTEMI in 67%, and STEMI in 26%. The NSTEMI patients were older, more frequently women, and had more comorbidities than patients with unstable angina pectoris and STEMI. At median follow-up of 3.2 years 195 patients had died: 14% of unstable angina pectoris, 45% of NSTEMI, and 25% of STEMI patients. Age-adjusted log-rank statistics revealed differences in mortality: NSTEMI vs unstable angina pectoris (P = .0091) and NSTEMI vs STEMI (P = .0045). The application of the universal definition together with the use of a contemporary troponin assay seems to have reduced the proportion of patients with unstable angina pectoris to the benefit of patients with NSTEMI. Despite this, NSTEMI patients have a sustained higher mortality than patients with STEMI. Copyright © 2015 Elsevier Inc. All rights reserved.

Multiple Species Comparison of Cardiac Troponin T and Dystrophin: Unravelling the DNA behind Dilated Cardiomyopathy.

Science.gov (United States)

England, Jennifer; Loughna, Siobhan; Rutland, Catrin Sian

2017-07-07

Animals have frequently been used as models for human disorders and mutations. Following advances in genetic testing and treatment options, and the decreasing cost of these technologies in the clinic, mutations in both companion and commercial animals are now being investigated. A recent review highlighted the genes associated with both human and non-human dilated cardiomyopathy. Cardiac troponin T and dystrophin were observed to be associated with both human and turkey (troponin T) and canine (dystrophin) dilated cardiomyopathies. This review gives an overview of the work carried out in cardiac troponin T and dystrophin to date in both human and animal dilated cardiomyopathy.

A practical approach for the validation and clinical implementation of a high-sensitivity cardiac troponin I assay across a North American city

Directory of Open Access Journals (Sweden)

Peter A. Kavsak

2015-04-01

Full Text Available Objectives: Despite several publications on the analytical performance of high-sensitivity cardiac troponin (hs-cTn assays, there has been little information on how laboratories should validate and implement these assays into clinical service. Our study provides a practical approach for the validation and implementation of a hs-cTn assay across a large North American City. Design and methods: Validation for the Abbott ARCHITECT hs-cTnI assay (across 5 analyzers consisted of verification of limit of blank (LoB, precision (i.e., coefficient of variation; CV testing at the reported limit of detection (LoD and within and outside the 99th percentile, linearity testing, cTnI versus hs-cTnI patient comparison within and between analyzers (Passing and Bablok and non-parametric analyses. Education, clinical communications, and memorandums were issued in advance to inform all staff across the city as well as a selected reminder the day before live-date to important users. All hospitals switched to the hs-cTnI assay concurrently (the contemporary cTnI assay removed with laboratory staff instructed to repeat samples previously measured with the contemporary cTnI assay with the hs-cTnI assay only by physician request. Results: Across the 5 analyzers and 6 reagent packs the overall LoB was 0.6 ng/L (n=60 with a CV of 33% at an overall mean of 1.2 ng/L (n=60; reported LoD=1.0 ng/L, with linearity demonstrated from 45,005 ng/L to 1.1 ng/L. Precision testing with a normal patient-pool QC material (mean range across 5 analyzers was 3.9–4.4 ng/L yielded a range of CVs from 7% to 10% (within-run and CVs from 7% to 18% (between-run with the high patient-pool QC material (mean range across 5 analyzers was 29.6–36.3 ng/L yielding a range of CVs from 2% to 5% (within-run and CVs from 4% to 8% (between-run. There was agreement between hs-cTnI versus cTnI with the patient samples (slope ranges: 0.89–1.03; intercept ranges: 1.9–3

Clinical features and prognosis of patients with acute non-specific chest pain in emergency and cardiology departments after the introduction of high-sensitivity troponins

DEFF Research Database (Denmark)

Ilangkovan, Nivethitha; Mickley, Hans; Diederichsen, Axel

2017-01-01

OBJECTIVES: To determine the incidence of clinical, cardiac-related endpoints and mortality among patients presenting to an emergency or cardiology department with non-specific chest pain (NSCP), and who receive testing with a high-sensitivity troponin. A second objective was to identify risk...... factors for the above-noted endpoints during 12 months of follow-up. DESIGN: A prospective multicentre study. SETTING: Emergency and cardiology departments in Southern Denmark. SUBJECTS: The study enrolled 1027 patients who were assessed for acute chest pain in an emergency or cardiology department...

Temporal seizure focus and status epilepticus are associated with high-sensitive troponin I elevation after epileptic seizures.

Science.gov (United States)

Chatzikonstantinou, Anastasios; Ebert, Anne D; Hennerici, Michael G

2015-09-01

Postictal elevation of high-sensitive troponin I (TNI), a highly specific biomarker for myocardial ischemia, has been reported. We aimed at evaluating its association of high-sensitive troponin I (TNI) with seizure type and focus, as well as vascular risk factors. TNI was measured in 247 patients admitted to our clinic via the emergency room with an acute epileptic seizure. TNI control measurements were performed in 61.5% of cases. All patients underwent electroencephalography and cerebral imaging. Seizure focus - when possible - was determined using results from these examinations as well as clinical data. Of 247 patients, 133 (53.8%) were men, the mean age was 59 ± 18 years. 70 (28.3%) patients had focal and 177 (71.7%) generalized seizures. Status epilepticus was present in 38 cases (15.4%). Mean TNI was 0.05 ± 0.17. TNI was elevated in 27 patients (10.9%). Higher age, status epilepticus and temporal seizure focus were significantly associated with TNI elevation in multivariate analysis. In 21 (13.8%) of the patients with TNI control measurement, TNI was continuously elevated. Higher age and temporal seizure focus were significantly associated with continuously high TNI. Coronary heart disease and vascular risk factors were significantly associated with high TNI only in univariate analysis. No patient had a symptomatic myocardial ischemia. Postictal TNI elevation is relatively common in older patients with status epilepticus or temporal seizure focus. These data support the concept of relevant and possibly dangerous ictal effects on cardiac function especially in temporal lobe seizures. Although the risk of manifest postictal myocardial infarction seems to be very low, selected patients could profit from closer monitoring. Copyright © 2015 Elsevier B.V. All rights reserved.

Multiple Species Comparison of Cardiac Troponin T and Dystrophin: Unravelling the DNA behind Dilated Cardiomyopathy

Directory of Open Access Journals (Sweden)

Jennifer England

2017-07-01

Full Text Available Animals have frequently been used as models for human disorders and mutations. Following advances in genetic testing and treatment options, and the decreasing cost of these technologies in the clinic, mutations in both companion and commercial animals are now being investigated. A recent review highlighted the genes associated with both human and non-human dilated cardiomyopathy. Cardiac troponin T and dystrophin were observed to be associated with both human and turkey (troponin T and canine (dystrophin dilated cardiomyopathies. This review gives an overview of the work carried out in cardiac troponin T and dystrophin to date in both human and animal dilated cardiomyopathy.

Diagnostic Utility of High Sensitivity Troponins for Echocardiographic Markers of Structural Heart Disease.

Science.gov (United States)

Wang, Tom Kai Ming; Dugo, Clementina; Gillian, Yvonne; Yvonne, Wynne; Heather, Semple; Kevin, Smith; Peter, Cleave; Jonathan, Christiansen; Andrew, To; Nezar, Amir; Scott, Tony; Ross, Boswell; Patrick, Gladding

2018-02-15

The conventional use of high-sensitivity troponins (hs-troponins) is for diagnosing myocardial infarction however they also have a role in chronic disease management. This pilot study assessed the relationship of hs-troponins with echocardiographic markers of left ventricular hypertrophy (LVH) and structural heart disease (SHD). Patients undergoing computer gomography (CT) coronary angiogram for low-intermediate risk chest pain and healthy volunteers were recruited. Hs-troponins Singulex I, Abbott I and Roche T and N-terminal pro-brain natriuretic peptide (NT-proBNP) were evaluated in relation to SHD parameters including left ventricular hypertrophy (LVH Echo ) and left atrial enlargement (LAE Echo ) on echocardiography. 78 subjects who underwent echocardiography were included in this study. C-statistics (95% confidence interval) of the four biomarkers for predicting LVH Echo were 0.84 (0.72-0.92), 0.84 (0.73-0.92), 0.75 (0.63-0.85) and 0.62 (0.49-0.74); for LAE Echo 0.74 (0.6-0.85), 0.78 (0.66-0.88), 0.55 (0.42-0.67) and 0.68 (0.62-0.85); and composite SHD 0.79 (0.66-0.88), 0.87 (0.75-0.94), 0.62 (0.49-0.73) and 0.74 (0.62-0.84) respectively. Optimal cut points for SHD were >1.2 ng/L, >1.6 ng/L, >8 ng/L and >18 pmol/L respectively. These results advocate the potential role of hs-troponins as screening tools for structural heart disease with theranostic implications.

Association between high-sensitive troponin I and coronary artery calcification in a Danish general population

DEFF Research Database (Denmark)

Olson, Fredrik; Engborg, Jonathan; Grønhøj, Mette H.

2016-01-01

BACKGROUND: High-sensitive troponin I (hs-TnI) is an individual predictor of future cardiovascular disease (CVD). However, the relationship between hs-TnI and coronary artery calcification (CAC) as determined by computed tomography (CT) has not previously been investigated in a general population...

Molecular and immunohistochemical analyses of cardiac troponin T during cardiac development in the Mexican axolotl, Ambystoma mexicanum.

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Zhang, C; Pietras, K M; Sferrazza, G F; Jia, P; Athauda, G; Rueda-de-Leon, E; Rveda-de-Leon, E; Maier, J A; Dube, D K; Lemanski, S L; Lemanski, L F

2007-01-01

The Mexican axolotl, Ambystoma mexicanum, is an excellent animal model for studying heart development because it carries a naturally occurring recessive genetic mutation, designated gene c, for cardiac nonfunction. The double recessive mutants (c/c) fail to form organized myofibrils in the cardiac myoblasts resulting in hearts that fail to beat. Tropomyosin expression patterns have been studied in detail and show dramatically decreased expression in the hearts of homozygous mutant embryos. Because of the direct interaction between tropomyosin and troponin T (TnT), and the crucial functions of TnT in the regulation of striated muscle contraction, we have expanded our studies on this animal model to characterize the expression of the TnT gene in cardiac muscle throughout normal axolotl development as well as in mutant axolotls. In addition, we have succeeded in cloning the full-length cardiac troponin T (cTnT) cDNA from axolotl hearts. Confocal microscopy has shown a substantial, but reduced, expression of TnT protein in the mutant hearts when compared to normal during embryonic development. 2006 Wiley-Liss, Inc.

Pragmatic approach to chest pain patients discharged with undetectable high-sensitivity troponin T and normal electrocardiogram: the STABS + CT protocol.

Science.gov (United States)

Bishop, Warrick; Girao, Gary

2017-06-01

A strategy that discharges chest pain patients with negative high-sensitivity troponin and non-ischaemic electrocardiography changes may still result in 0.44% of patients experiencing myocardial infarction within 30 days. We observed that a pragmatic approach that systematically discharged 25 patients on cardio-protective medications of aspirin, metoprolol and atorvastatin followed with prompt (<10 days) coronary computed tomography angiography resulted in no major adverse cardiac event and adverse drug reaction 30 days post-presentation. The strategy resulted in three patients (12%) ultimately diagnosed with likely unstable angina, which required planned coronary intervention in two patients and medical management in one patient. No unplanned readmissions for chest pains were noted from initial presentation through to 6-month follow up. © 2017 Royal Australasian College of Physicians.

Impact of statin use on exercise-induced cardiac troponin elevations.

NARCIS (Netherlands)

Eijsvogels, T.M.H.; Januzzi, J.L., Jr.; Taylor, B.A.; Isaacs, S.K.; D'Hemecourt, P.; Zaleski, A.; Dyer, S.; Troyanos, C.; Weiner, R.B.; Thompson, P.D.; Baggish, A.L.

2014-01-01

Marathon running commonly causes a transient elevation of creatine kinase and cardiac troponin I (cTnI). The use of statins before marathon running exacerbates the release of creatine kinase from skeletal muscle, but the effect of statin use on exercise-induced cTnI release is unknown. We therefore

Falsely elevated troponin: rare occurrence or future problem

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James Nguyen

2016-12-01

Full Text Available Introduction: Troponins are known to be released in response to cardiac damage and therefore are the biomarkers of choice for the early diagnosis of acute myocardial infarction (AMI, improving outcome in patients presenting with chest pain. However, false results can occur due to interference from other substances in the blood. Case: A 52-year-old male with a past medical history of alcohol abuse, hypertension, and coronary artery bypass graft at age 34 with normal stress test 2 years before presented to the emergency department (ED complaining of 1 day of non-exertional chest pain with radiation to the neck and left arm. His troponin was elevated to 5 ng/mL in two samples drawn 12 h apart, with normal CK-MB. Renal function was normal. Electrocardiogram (ECG showed normal sinus rhythm with no ST elevations or depressions. He underwent cardiac catheterization which showed no obstructive lesions. Five years later, he returned to the ED with abdominal pain and shortness of breath. Troponin was elevated and showed no signs of downtrend on repeat every 6 h. ECG was unchanged from 5 years before. He was discharged with a follow-up cardiac computed tomography (CT. Troponin was measured on the day of his scan and remained elevated; he was asymptomatic. Cardiac CT showed unremarkable coronaries and bypass grafts. Given persistently positive troponin in the setting of minimal to no symptoms, he was thought to have falsely elevated troponins. Centrifugation and 2:1 dilution of the sample resulted in the same general value, respectively. Rheumatoid factor and heterophile antibodies were negative. When his blood sample was sent to a different hospital utilizing a three-site immunoassay method, the value was found zero. Discussion: Cardiac troponins (cTn are structural proteins unique to the heart, not expressed outside of cardiac tissue and have high sensitivity and specificity for myocardial damage. Therefore, it is the test of choice for the diagnosis of

High?Sensitivity Troponin: A Clinical Blood Biomarker for Staging Cardiomyopathy in Fabry Disease

OpenAIRE

2016-01-01

Background High?sensitivity troponin (hs?TNT), a biomarker of myocardial damage, might be useful for assessing fibrosis in Fabry cardiomyopathy. We performed a prospective analysis of hs?TNT as a biomarker for myocardial changes in Fabry patients and a retrospective longitudinal follow?up study to assess longitudinal hs?TNT changes relative to fibrosis and cardiomyopathy progression. Methods and Results For the prospective analysis, hs?TNT from 75 consecutive patients with genetically confirm...

Changes in the dynamics of the cardiac troponin C molecule explain the effects of Ca2+-sensitizing mutations.

Science.gov (United States)

Stevens, Charles M; Rayani, Kaveh; Singh, Gurpreet; Lotfalisalmasi, Bairam; Tieleman, D Peter; Tibbits, Glen F

2017-07-14

Cardiac troponin C (cTnC) is the regulatory protein that initiates cardiac contraction in response to Ca 2+ TnC binding Ca 2+ initiates a cascade of protein-protein interactions that begins with the opening of the N-terminal domain of cTnC, followed by cTnC binding the troponin I switch peptide (TnI SW ). We have evaluated, through isothermal titration calorimetry and molecular-dynamics simulation, the effect of several clinically relevant mutations (A8V, L29Q, A31S, L48Q, Q50R, and C84Y) on the Ca 2+ affinity, structural dynamics, and calculated interaction strengths between cTnC and each of Ca 2+ and TnI SW Surprisingly the Ca 2+ affinity measured by isothermal titration calorimetry was only significantly affected by half of these mutations including L48Q, which had a 10-fold higher affinity than WT, and the Q50R and C84Y mutants, each of which had affinities 3-fold higher than wild type. This suggests that Ca 2+ affinity of the N-terminal domain of cTnC in isolation is insufficient to explain the pathogenicity of these mutations. Molecular-dynamics simulation was used to evaluate the effects of these mutations on Ca 2+ binding, structural dynamics, and TnI interaction independently. Many of the mutations had a pronounced effect on the balance between the open and closed conformations of the TnC molecule, which provides an indirect mechanism for their pathogenic properties. Our data demonstrate that the structural dynamics of the cTnC molecule are key in determining myofilament Ca 2+ sensitivity. Our data further suggest that modulation of the structural dynamics is the underlying molecular mechanism for many disease mutations that are far from the regulatory Ca 2+ -binding site of cTnC. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Point-of-care heart-type fatty acid binding protein versus high-sensitivity troponin T testing in emergency patients at high risk for acute coronary syndrome.

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Kellens, Sebastiaan; Verbrugge, Frederik H; Vanmechelen, Maxime; Grieten, Lars; Van Lierde, Johan; Dens, Joseph; Vrolix, Mathias; Vandervoort, Pieter

2016-04-01

High-sensitivity cardiac troponin testing is used to detect myocardial damage in patients with acute chest pain. Heart-type fatty acid binding protein (H-FABP) may be an alternative, available as point-of-care test. Patients (n=203) referred by general practitioners for suspected acute coronary syndrome or presenting with typical chest pain and one major cardiovascular risk factor at the emergency department were prospectively included in a single-centre cohort study. High-sensitivity cardiac troponin T (hs-TnT) and point-of-care H-FABP testing were concomitantly performed at admission and after 6h. Maximal hs-TnT levels above the 99th percentile were observed in 152 patients (75%) with 127 (63%) fulfilling criteria for myocardial infarction. Upon admission, hs-TnT and H-FABP were associated with an area under the curve (95% CI) of 0.83 (0.77-0.89) and 0.79 (0.73-0.85), respectively, to predict myocardial infarction, which increased to 0.93 (0.90-0.97) and 0.88 (0.84-0.93), respectively, after 6h. The diagnostic accuracy for non-ST-segment elevation myocardial infarction was somewhat lower with an area under the curve (95% CI) of 0.80 (0.72-0.87), 0.90 (0.84-0.96), 0.73 (0.64-0.81) and 0.77 (0.67-0.86), respectively. When assessment was performed within 3h of chest pain onset, diagnostic accuracy of H-FABP versus hs-TnT was similar. Each standard deviation increase in admission H-FABP was associated with a 68% relative risk increase of all-cause mortality (p-value=0.027) during 666 ± 155 days of follow-up. Point-of-care H-FABP testing has lower diagnostic accuracy compared with hs-TnT assessment in patients with high pre-test acute coronary syndrome probability, but might be of interest when assessment is possible early after chest pain onset. © The European Society of Cardiology 2015.

Prediction of outcome by highly sensitive troponin T in outpatients with chronic systolic left ventricular heart failure

DEFF Research Database (Denmark)

Egstrup, Michael; Schou, Morten; Tuxen, Christian D

2012-01-01

Our aim was to assess the prognostic impact of a high-sensitivity cardiac troponin T (hs-cTnT) assay in an outpatient population with chronic systolic left ventricular heart failure (HF). Four hundred sixteen patients with chronic HF and left ventricular ejection fraction ≤ 45% were enrolled...... in a prospective cohort study. In addition to hs-cTnT, plasma amino-terminal pro-B-type natriuretic peptide was measured at baseline. Mean age was 71 years, 29% were women, 62% had coronary artery disease (CAD), mean left ventricular ejection fraction was 31%, and 57% had abnormal level of hs-cTnT. During 4.......4 years of follow-up, 211 (51%) patients died. In multivariate Cox regression models, hs-cTnT was categorized as quartiles or dichotomized by the 99th percentile of a healthy population. Adjusted hazard ratios for all-cause mortality for quartiles 2 to 4, with quartile 1 as reference, were 1.4 (95...

Troponin and anti-troponin autoantibody levels in patients with ventricular noncompaction.

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Hatice Betül Erer

Full Text Available Ventricular hypertrabeculation/noncompaction is a morphologic and functional anomaly of myocardium characterized by prominent trabeculae accompanied by deep recessus. Dilated cardiomyopathy with left ventricular failure is observed in these patients, while the cause or pathophysiologic nature of this complication is not known. Anti-troponin antibodies are formed against circulating cardiac troponins after an acute coronary event or conditions associated with chronic myocyte necrosis, such as dilated cardiomyopathy. In present study, we aimed to investigate cardiac troponins and anti troponin autoantibodies in ventricular noncompaction/hypertrabeculation patients with/without reduced ejection fraction. A total of 50 patients with ventricular noncompaction and 23 healthy volunteers were included in this study. Noncompaction/hypertrabeculation was diagnosed with two-dimensional echocardiography using appropriate criteria. Depending on ejection fraction, patients were grouped into noncompaction with preserved EF (LVEF >50%, n = 24 and noncompaction with reduced EF (LVEF <35%, n = 26 groups. Troponin I, troponin T, anti-troponin I IgM and anti-troponin T IgM were measured with sandwich immunoassay method using a commercially available kit. Patients with noncompaction had significantly higher troponin I (28.98±9.21 ng/ml in NCNE group and 28.11±10.42 ng/ml in NCLE group, troponin T (22.17±6.97 pg/ml in NCNE group and 22.78±7.76 pg/ml in NCLE group and antitroponin I IgM (1.92±0.43 µg/ml in NCNE group and 1.79±0.36 µg/ml in NCLE group levels compared to control group, while antitroponin T IgM and IgG were only elevated in patients with noncompaction and reduced EF (15.81±6.52 µg/ml for IgM and 16.46±6.25 µg/ml for IgG. Elevated cardiac troponins and anti-troponin I autoantibodies were observed in patients with noncompaction preceding the decline in systolic function and could indicate ongoing myocardial damage in these patients.

Troponin and Anti-Troponin Autoantibody Levels in Patients with Ventricular Noncompaction

Science.gov (United States)

Erer, Hatice Betül; Güvenç, Tolga Sinan; Kemik, Ahu Sarbay; Yılmaz, Hale Yaka; Kul, Şeref; Altay, Servet; Sayar, Nurten; Kaya, Yüksel; Eren, Mehmet

2013-01-01

Ventricular hypertrabeculation/noncompaction is a morphologic and functional anomaly of myocardium characterized by prominent trabeculae accompanied by deep recessus. Dilated cardiomyopathy with left ventricular failure is observed in these patients, while the cause or pathophysiologic nature of this complication is not known. Anti-troponin antibodies are formed against circulating cardiac troponins after an acute coronary event or conditions associated with chronic myocyte necrosis, such as dilated cardiomyopathy. In present study, we aimed to investigate cardiac troponins and anti troponin autoantibodies in ventricular noncompaction/hypertrabeculation patients with/without reduced ejection fraction. A total of 50 patients with ventricular noncompaction and 23 healthy volunteers were included in this study. Noncompaction/hypertrabeculation was diagnosed with two-dimensional echocardiography using appropriate criteria. Depending on ejection fraction, patients were grouped into noncompaction with preserved EF (LVEF >50%, n = 24) and noncompaction with reduced EF (LVEF <35%, n = 26) groups. Troponin I, troponin T, anti-troponin I IgM and anti-troponin T IgM were measured with sandwich immunoassay method using a commercially available kit. Patients with noncompaction had significantly higher troponin I (28.98±9.21 ng/ml in NCNE group and 28.11±10.42 ng/ml in NCLE group), troponin T (22.17±6.97 pg/ml in NCNE group and 22.78±7.76 pg/ml in NCLE group) and antitroponin I IgM (1.92±0.43 µg/ml in NCNE group and 1.79±0.36 µg/ml in NCLE group) levels compared to control group, while antitroponin T IgM and IgG were only elevated in patients with noncompaction and reduced EF (15.81±6.52 µg/ml for IgM and 16.46±6.25 µg/ml for IgG). Elevated cardiac troponins and anti-troponin I autoantibodies were observed in patients with noncompaction preceding the decline in systolic function and could indicate ongoing myocardial damage in these patients. PMID:23469039

Performance characteristics of loci method for measuring cardiac troponin I on the dimension EXL

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José L. Martín Calderón

2015-04-01

Full Text Available Objective: To define the performance characteristics of the LOCI® method for cardiac troponin I on the Dimension EXL system. Designs and methods: Three different levels of commercial control (mean concentrations 0.426, 1.42, and 18.64 µg/L were used for the imprecision study, quantifying separately within-run and between-run over 20 days. The limit of blank (LoB and limit of detection (LoD were assessed with 20 replicates of a sample without troponin I. Linearity was assessed by regression analysis. In addition, we studied inaccuracy, carry-over and limit of quantitation and conducted a method comparison with the Stratus CS (n=69. The reference interval was determined in 146 healthy blood donors using non-parametric method. Results: The within-run imprecision (coefficient of variation [CV], % obtained at each level was 2.4, 1.4% and 2.2%, while the between-run imprecision (CV,% was 3.3%, 2.9% and 2.5%. Total imprecision was 4.06%, 3.3% and 3.4% for each control level. The limit of quantitation which corresponds to the troponin I concentration at which CV=10% was 0.05 µg/L. Method comparison with the Stratus CS assay produced the equation: Dimension EXL=−0.002698+1.0233⁎(Stratus CS with a confidence interval from −0.01562 to 0.00626 for the intercept and (0.979 to 1.0875 for the slope. The 99th percentile obtained for the reference population was 0.047 µg/L. Conclusions: The LOCI method for cardiac troponin I on the Dimension EXL meets all guidelines recommended criteria referring to limit of quantitation, imprecision and shows excellent transferability with the Stratus CS method. Keywords: Cardiac troponin, LOCI, Dimension EXL

Cardiac magnetic resonance imaging in patients with chest pain, high troponin levels and absence of coronary artery obstruction

International Nuclear Information System (INIS)

Avegliano, G.P.; Costabel, J.P.; Kuschnir, P.; Thierer, J.; Alves de Lima, A.; Sanchez, G.; Ronderos, J.; Huguet, M.; Petit, M.; Frangi, A.A.

2011-01-01

The prevalence of myocardial infarction with angiographically normal coronary arteries is approximately 7-10%. The etiological diagnosis is sometimes difficult and is important in terms of clinical practice and prognosis. The goal of our study was to show a series of consecutive patients with an initial diagnosis of acute coronary syndrome with high troponin levels and absence of coronary artery obstruction in which cardiac magnetic resonance imaging (CMRI) gave a description of the myocardial lesion, orientating towards the etiological diagnosis. From January 2005 to December 2009, 720 consecutive patients with an initial diagnosis of acute coronary syndrome and elevated troponins were included; 64 of these patients did not present angiographically significant coronary artery stenosis. Within 72 ± 24 h after coronary angiography, these patients underwent CMRI using b-SSFP sequences for cine imaging in short-axis, 2-, 3- and 4- chamber views for the evaluation of segmental wall motion, with T2-weighted and delayed enhancement (DE) images of the myocardium with an 'inversion-recovery' sequence. The following diagnoses were made: myocarditis (39 patients); myocardial infarction (12 patients); Tako-Tsubo syndrome (8 patients); apical hypertrophic cardiomyopathy (2 patients); 3 patients remained without diagnosis. These findings demonstrate the usefulness of CMRI in the clinical scenario of patients with chest pain, inconclusive ECG findings and high troponin levels with angiographically normal coronary arteries. The presence and distribution pattern of DE make it possible to define the etiological diagnosis and interpret the physiopathological process. (authors) [es

Serum cardiac troponin I in canine syncope and seizures.

Science.gov (United States)

Dutton, E; Dukes-McEwan, J; Cripps, P J

2017-02-01

To determine if serum cardiac troponin I (cTnI) concentration distinguishes between cardiogenic syncope and collapsing dogs presenting with either generalized epileptic seizures (both with and without cardiac disease) or vasovagal syncope. Seventy-nine prospectively recruited dogs, grouped according to aetiology of collapse: generalized epileptic seizures (group E), cardiogenic syncope (group C), dogs with both epileptic seizures and cardiac disease (group B), vasovagal syncope (group V) or unclassified (group U). Most patients had ECG (n = 78), echocardiography (n = 78) and BP measurement (n = 74) performed. Dogs with a history of intoxications, trauma, evidence of metabolic disorders or renal insufficiency (based on serum creatinine concentrations >150 μmol/L and urine specific gravity disease) or vasovagal syncope. Copyright © 2016 Elsevier B.V. All rights reserved.

N-terminal Pro-brain Natriuretic Peptide, High-sensitivity Troponin and Pulmonary Artery Clot Score as Predictors of Right Ventricular Dysfunction in Echocardiography.

Science.gov (United States)

Granér, Marit; Harjola, Veli-Pekka; Selander, Tuomas; Laiho, Mia K; Piilonen, Anneli; Raade, Merja; Mustonen, Pirjo

2016-06-01

We investigated the ability of cardiac biomarkers and total pulmonary artery (PA) clot score to predict right ventricular dysfunction (RVD) on admission and at seven-month follow-up in subjects with acute pulmonary embolism (APE). Sixty-three normotensive patients with APE were divided into two groups: patients with (n= 32, age 58±19 years) and without (n=31, age 55±16 years) echocardiographic RVD. Transthoracic echocardiography (TTE), N-terminal pro-brain natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hsTnT) were assessed upon arrival and repeated at seven months. Total PA clot score was determined on admission. The age- and sex dependent NT-proBNP on admission, on day 5, and at seven months exhibited the best sensitivity (admission 94%, day 5 100%, seven months 100%) and negative predictive value (NPV) (89%, 100%, 100%) for detecting RVD. Six patients (10%) had persistent RVD at seven months. Total PA clot score showed only low to moderate sensitivity (77%) and PPV (7%) for detection of RVD at seven months. Normal age- and sex dependent NT-proBNP on admission or measured five days later seems to be useful in exclusion of RVD at follow up. Total PA clot score shows only to be of modest benefit for predicting persistent RVD. Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Association of cardiac troponin I with disease severity and outcomes in patients with pulmonary hypertension.

Science.gov (United States)

Vélez-Martínez, Mariella; Ayers, Colby; Mishkin, Joseph D; Bartolome, Sonja B; García, Christine K; Torres, Fernando; Drazner, Mark H; de Lemos, James A; Turer, Aslan T; Chin, Kelly M

2013-06-15

Previous studies have identified cardiac troponin I (cTnI) as an important marker in pulmonary hypertension (PH) prognosis. However, traditional assays are limited by poor sensitivity, even among patients at high risk. cTnI was measured in 255 PH patients using a new highly sensitive (hs) assay. Other measures included demographics, creatinine, 6-minute walk distance, hemodynamics, cardiac magnetic resonance imaging, and B-type natriuretic peptide level. The association between cTnI and survival was assessed using Kaplan-Meier analysis and Cox regression. cTnI was detectable with the hs assay in 95% of the patients with a median level of 6.9 pg/ml (IQR 2.7-12.6 pg/ml). Higher cTnI levels associated with higher levels of B-type natriuretic peptide, shorter 6-minute walk distance, and more severe hemodynamic and cardiac magnetic resonance imaging abnormalities. During a median follow-up of 3.5 years, 60 individuals died. Unadjusted event rates increased across higher cTnI quartiles (3, 5, 13, 17 events/100 person-years, respectively, p trend = 0.002). cTnI in the fourth (vs first) quartile remained associated with death in a final stepwise multivariable model that included clinical variables and hemodynamics (adjusted hazard ratio 5.3, 95% confidence interval 1.8-15.6). In conclusion, cTnI levels, detectable with a novel hs assay, identify patients with PH who have more severe hemodynamic and cardiac structural abnormalities and provide novel and independent prognostic information. This hs assay has the potential to detect more at-risk patients and improve current risk-stratification algorithms. Copyright © 2013 Elsevier Inc. All rights reserved.

Sex differences of troponin test performance in chest pain patients.

Science.gov (United States)

Slagman, Anna; Searle, Julia; Vollert, Jörn O; Storchmann, Harald; Büschenfelde, Dirk Meyer Zum; von Recum, Johannes; Vlasny, Daniela; Ale-Abaei, Angela; Koch, Matthias; Müller, Christian; Müller, Reinhold; Somasundaram, Rajan; Möckel, Martin

2015-01-01

Current guidelines recommend troponin as the preferred biomarker to diagnose acute myocardial infarction (AMI) irrespective of the patient's sex. Recent reports have shown that sex-specific cut-offs should be considered but studies investigating sex-differences in the diagnostic accuracy of cardiac troponins are sparse. To evaluate whether the diagnostic performance of cardiac troponin at admission (cTn) under routine conditions is influenced by patient's sex. Between 15th of February 2009 and 15th of February 2010, women (n=1648) and men (n=2305) who presented to the emergency department with chest pain (n=3954) were enrolled. The diagnostic performance of the routine, contemporary sensitive cTn assays (TnI; Stratus® CS, Siemens and TnT; Roche Diagnostics) at baseline for the diagnosis of non-ST-elevation myocardial infarction (NSTEMI) was analyzed. NSTEMI was diagnosed in 7.3% (n=287) of all patients. Men were more likely to be diagnosed with NSTEMI (8.8%; n=202) as compared to women (5.2%; n=85; psex, with a lower sensitivity and NPV in women. The definition and implementation of sex-specific cut-off values for cTn into clinical routine seems to be highly recommendable. Copyright © 2015. Published by Elsevier Ireland Ltd.

NT-proBNP and troponin T levels differ after haemodialysis with a low versus high flux membrane

OpenAIRE

Laveborn, Emilie; Lindmark, Krister; Skagerlind, Malin; Stegmayr, Bernd

2015-01-01

BACKGROUND: Brain natriuretic peptide (BNP), N-terminal-proBNP (NT-proBNP), and high sensitive cardiac troponin T (TnT) are markers that are elevated in chronic kidney disease and correlate with increased risk of mortality. Data are conflicting on the effect of biomarker levels by hemodialysis (HD).Our aim was to clarify to what extent HD with low-flux (LF) versus high-flux (HF) membranes affects the plasma levels of BNP, NT-proBNP, and TnT. METHODS AND MATERIALS: 31 HD patients were included...

Motor neurone disease presenting with raised serum Troponin T.

Science.gov (United States)

Mamo, Jonathan P

2015-05-01

Myocardial damage indicated by a rise in cardiac Troponin may not necessarily be due to a cardiac event. Many diseases such as sepsis, pulmonary embolism, heart and renal failure can also be associated with an elevated cardiac Troponin level. This brief report discusses the rare event of a patient with motor neurone disease, where the possible diagnosis of acute myocardial infarction arose due to an elevated cardiac Troponin. A 69-year-old gentleman presented with a history of a central chest ache of mild intensity, lasting a total of 2 h prior to complete resolution. Multiple cardiac Troponin assays were elevated, and echocardiography did not show any acute changes of myocardial damage. His electrocardiogram was also normal. This patient's raised cardiac Troponin was therefore explained on the basis of his active motor neurone disease. This rare case outlines the importance of considering motor neurone disease as a cause of elevated cardiac Troponin in the absence of clinical evidence of an acute coronary event. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Troponin and exercise.

Science.gov (United States)

Gresslien, T; Agewall, S

2016-10-15

Cardiac troponins are the preferred biomarkers in diagnostic of myocardial infarction, but these markers also can rise in response to exercise. Multiple studies have assessed troponins post-exercise, but the results have varied and there have been disagreements about the mechanism of troponin release. The aim of this paper was to review the literature, and to consider factors and mechanisms regarding exercise-induced increase of troponin. 145 studies were found after a search in pubmed and inclusion of additional articles found in the reference list of the first articles. Results showed that troponin rises in 0-100% of subjects after prolonged heavy exercise like marathon, but also after short-term and intermittent exercise like 30min of running and basketball. The variation can be due to factors like intensity, age, training experience, variation in sample size, blood sample timing and troponin assay. The pattern of troponin level post-exercise corresponds to release from the cytosolic compartment of cardiomyocytes. Increased membrane permeability might be caused by production of reactive oxygen species or alterations in calcium, pH, glucose/fat metabolism or in communication between integrins. Other suggested mechanisms are increased cardiovascular stress, inflammation, vasculitis, release of troponin degradation products in "blebs", dehydration, impaired renal clearance and expression of cardiac troponin in skeletal muscle. It can be concluded that both heavy and light exercise may cause elevated troponin, which have to be considered when patient are suspected to have a myocardial infarction. Several factors probably influence post-exercise levels of troponin, but the mechanism of release is most likely physiologic. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Performance of highly sensitive cardiac troponin T assay to detect ischaemia at PET-CT in low-risk patients with acute coronary syndrome: a prospective observational study.

Science.gov (United States)

Morawiec, Beata; Fournier, Stephane; Tapponnier, Maxime; Prior, John O; Monney, Pierre; Dunet, Vincent; Lauriers, Nathalie; Recordon, Frederique; Trana, Catalina; Iglesias, Juan-Fernando; Kawecki, Damian; Boulat, Olivier; Bardy, Daniel; Lamsidri, Sabine; Eeckhout, Eric; Hugli, Olivier; Muller, Olivier

2017-07-10

Highly sensitive troponin T (hs-TnT) assay has improved clinical decision-making for patients admitted with chest pain. However, this assay's performance in detecting myocardial ischaemia in a lowrisk population has been poorly documented. To assess hs-TnT assay's performance to detect myocardial ischaemia at positron emission tomography/CT (PET-CT) in low-risk patients admitted with chest pain. Patients admitted for chest pain with a nonconclusive ECG and negative standard cardiac troponin T results at admission and after 6 hours were prospectively enrolled. Their hs-TnT samples were at T0, T2 and T6. Physicians were blinded to hs-TnT results. All patients underwent a PET-CT at rest and during adenosine-induced stress. All patients with a positive PET-CT result underwent a coronary angiography. Forty-eight patients were included. Six had ischaemia at PET-CT. All of them had ≥1 significant stenosis at coronary angiography. Areas under the curve (95% CI) for predicting significant ischaemia at PET-CT using hs-TnT were 0.764 (0.515 to 1.000) at T0, 0.812(0.616 to 1.000) at T2 and 0.813(0.638 to 0.989) at T6. The receiver operating characteristicbased optimal cut-off value for hs-TnT at T0, T2 and T6 needed to exclude significant ischaemia at PET-CT was <4 ng/L. Using this value, sensitivity, specificity, positive and negative predictive values of hs-TnT to predict significant ischaemia were 83%/38%/16%/94% at T0, 100%/40%/19%/100% at T2 and 100%/43%/20%/100% at T6, respectively. Our findings suggest that in low-risk patients, using the hs-TnT assay with a cut-off value of 4 ng/L demonstrates excellent negative predictive value to exclude myocardial ischaemia detection at PET-CT, at the expense of weak specificity and positive predictive value. ClinicalTrials.gov Identifier: NCT01374607. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly

Baseline cardiac troponin t levels are elevated in subjects with untreated diabetes mellitus

DEFF Research Database (Denmark)

Pareek, M; Nielsen, M L; Leósdóttir, M

2015-01-01

Objective: Cardiac troponins are biomarkers of myocardial injury and serve both diagnostic and prognostic purposes. Even mild elevations represent subclinical myocardial damage in the general population. The objective of this study was to investigate the relationship between glucometabolic status...

Serum cardiac troponin I in acute stroke is related to serum cortisol and TNF-alpha

DEFF Research Database (Denmark)

Christensen, Hanne Krarup; Johannesen, Helle Hjorth; Christensen, Anders Fogh

2004-01-01

Serum cardiac troponin I (cTnI) is a specific marker of myocardial injury related to in-patient fatality and cardiac injury in acute stroke. We investigated whether cTnI in acute stroke is related to serum cortisol, acute inflammatory response, and insular damage. We also investigated whether c...

Multiple species comparison of cardiac troponin T and dystrophin: unravelling the DNA behind dilated cardiomyopathy

OpenAIRE

England, Jennifer; Loughna, Siobhan; Rutland, Catrin S.

2017-01-01

Animals have frequently been used as models for human disorders and mutations. Following advances in genetic testing and treatment options, and the decreasing cost of these technologies in the clinic, mutations in both companion and commercial animals are now being investigated. A recent review highlighted the genes associated with both human and non-human dilated cardiomyopathy. Cardiac troponin T and dystrophin were observed to be associated with both human and turkey (troponin T) and canin...

N-terminal pro-brain natriuretic peptide and high-sensitivity troponin T exhibit additive prognostic value for the outcome of critically ill patients.

Science.gov (United States)

Lenz, Max; Krychtiuk, Konstantin A; Goliasch, Georg; Distelmaier, Klaus; Wojta, Johann; Heinz, Gottfried; Speidl, Walter S

2018-04-01

Patients treated at medical intensive care units suffer from various pathologies and often present with elevated troponin T (TnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Both markers may reflect different forms of cardiac involvement in critical illness. Therefore, the aim of our study was to examine the synergistic prognostic potential of NT-proBNP and high-sensitivity TnT (hs)TnT in unselected critically ill patients. We included all consecutive patients admitted to our intensive care unit within one year, excluding those suffering from acute myocardial infarction or undergoing cardiac surgery and measured NT-proBNP and TnT plasma levels on the day of admission and 72 hours thereafter. Of the included 148 patients, 52% were male, mean age was of 64.2 ± 16.8 years and 30-day mortality was 33.2%. Non-survivors showed significantly higher NT-proBNP and TnT plasma levels as compared with survivors ( pvalue. This might be attributed to a difference in underlying pathomechanisms and an assessment of synergistic risk factors.

Assessment of the 2016 National Institute for Health and Care Excellence high-sensitivity troponin rule-out strategy

Science.gov (United States)

Greenslade, Jaimi; Cullen, Louise; Than, Martin; Kendall, Jason; Body, Richard; Parsonage, William A; Khattab, Ahmed

2018-01-01

Objective We aimed to evaluate the limit of detection of high-sensitivity troponin (hs-cTn) and Thrombolysis In Myocardial Infarction (TIMI) score combination rule-out strategy suggested within the 2016 National Institute for Health and Care Excellence (NICE) Chest Pain of Recent Onset guidelines and establish the optimal TIMI score threshold for clinical use. Methods A pooled analysis of adult patients presenting to the emergency department with chest pain and a non-ischaemic ECG, recruited into six prospective studies, from Australia, New Zealand and the UK. We evaluated the sensitivity of TIMI score thresholds from 0 to 2 alongside hs-cTnT or hs-cTnI for the primary outcome of major adverse cardiac events within 30 days. Results Data were available for 3159 patients for hs-cTnT and 4532 for hs-cTnI, of these 376 (11.9%) and 445 (9.8%) had major adverse cardiac events, respectively. Using a TIMI score of 0, the sensitivity for the primary outcome was 99.5% (95% CI 98.1% to 99.9%) alongside hs-cTnT and 98.9% (97.4% to 99.6%)%) alongside hs-cTnI, identifying 17.9% and 21.0% of patients as low risk, respectively. For a TIMI score ≤1 sensitivity was 98.9% (97.3% to 99.7%)%) alongside hs-cTnT and 98.4% (96.8% to 99.4%)%) alongside hs-cTnI, identifying 28.1% and 35.7% as low risk, respectively. For TIMI≤2, meta-sensitivity was <98% with either assay. Conclusions Our findings support the rule-out strategy suggested by NICE. The TIMI score threshold suggested for clinical use is 0. The proportion of patients identified as low risk (18%–21%) and suitable for early discharge using this threshold may be sufficient to encourage change of practice. Trial registration numbers ADAPT observational study/IMPACT intervention trial ACTRN12611001069943. ADAPT-ADP randomised controlled trial ACTRN12610000766011. EDACS-ADP randomised controlled trial ACTRN12613000745741. TRUST observational study ISRCTN no. 21109279. PMID:28864718

Single histidine button in cardiac troponin I sustains heart performance in response to severe hypercapnic respiratory acidosis in vivo.

Science.gov (United States)

Palpant, Nathan J; D'Alecy, Louis G; Metzger, Joseph M

2009-05-01

Intracellular acidosis is a profound negative regulator of myocardial performance. We hypothesized that titrating myofilament calcium sensitivity by a single histidine substituted cardiac troponin I (A164H) would protect the whole animal physiological response to acidosis in vivo. To experimentally induce severe hypercapnic acidosis, mice were exposed to a 40% CO(2) challenge. By echocardiography, it was found that systolic function and ventricular geometry were maintained in cTnI A164H transgenic (Tg) mice. By contrast, non-Tg (Ntg) littermates experienced rapid and marked cardiac decompensation during this same challenge. For detailed hemodymanic assessment, Millar pressure-conductance catheterization was performed while animals were treated with a beta-blocker, esmolol, during a severe hypercapnic acidosis challenge. Survival and load-independent measures of contractility were significantly greater in Tg vs. Ntg mice. This assay showed that Ntg mice had 100% mortality within 5 min of acidosis. By contrast, systolic and diastolic function were protected in Tg mice during acidosis, and they had 100% survival. This study shows that, independent of any beta-adrenergic compensation, myofilament-based molecular manipulation of inotropy by histidine-modified troponin I maintains cardiac inotropic and lusitropic performance and markedly improves survival during severe acidosis in vivo.

Risk stratification in stable coronary artery disease is possible at cardiac troponin levels below conventional detection and is improved by use of N-terminal pro-B-type natriuretic peptide

DEFF Research Database (Denmark)

Lyngbæk, Stig; Winkel, Per; Gøtze, Jens P

2014-01-01

AIMS: Low prevalence of detectable cardiac troponin in healthy people and low-risk patients previously curtailed its use. With a new high-sensitive cardiac troponin assay (hs-cTnT), concentrations below conventional detection may have prognostic value, notably in combination with N-terminal pro......-B-type natriuretic peptide (NT-pro-BNP). METHODS AND RESULTS: Biomarker concentrations were determined from serum obtained at enrolment in the CLARICOR trial involving 4197 patients with stable coronary artery disease (CAD) followed for 2.6 years. Serum hs-cTnT was detectable (above 3 ng/l) in 78% and above...... the conventional 99th percentile (13.5 ng/l) in 23%. Across all levels of hs-cTnT there was a graded increase in the risk of cardiovascular death after adjustment for known prognostic indicators: hazard ratio (HR) per unit increase in the natural logarithm of the hs-cTnT level, 1.49; 95% confidence interval (CI...

Impact of high-sensitivity cardiac troponin I assays on patients presenting to an emergency department with suspected acute coronary syndrome.

Science.gov (United States)

Yip, Thomas P Y; Pascoe, Heather M; Lane, Stephen E

2014-08-04

To determine whether introduction of high-sensitivity cardiac troponin I (hscTn-I) assays affected management of patients presenting with suspected acute coronary syndrome (ACS) to the emergency department (ED) of a tertiary referral hospital. A retrospective analysis of all patients presenting to the Geelong Hospital ED with suspected ACS from 23 April 2010 to 22 April 2013 -2 years before and 1 year after the changeover to hscTn-I assays on 23 April 2012. Hospital admission rates, time spent in the ED, rates of coronary angiography, rates of percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABGS), rates of discharge with a diagnosis of ACS, and rates of inhospital mortality. 12 360 consecutive patients presented with suspected ACS during the study period; 1897 were admitted to Geelong Hospital in the 2 years before and 944 in the 1 year after the changeover to hscTn-I assays. Comparing the two patient groups, there was no statistically significant difference in all-hospital admission rates (95% CI for the difference, - 3.1% to 0.3%; P = 0.10) or proportion of patients subsequently discharged with a diagnosis of ACS (95% CI for the difference, - 2.3% to 5.4%; P = 0.43). After the changeover, the median time patients spent in the ED was 11.5% shorter (3.85 h v 4.35 h; 95% CI for the difference, - 0.59 to - 0.43; P rise in the proportion of patients who had invasive treatment (PCI and/or CABGS) (95% CI for the difference, - 0.4% to 6.3%; P = 0.08). Inhospital mortality rates from ACS did not change significantly (95% CI for the difference, - 1.5% to 0.8%; P = 0.43). The introduction of hscTn-I assays appeared to be associated with more rapid diagnosis, resulting in less time spent in the ED, without a change in hospital admission rates. A higher proportion of patients had coronary angiographies after the changeover, but there was no significant change in rates of invasive treatment or inhospital mortality.

Analytical evaluation of a new point of care system for measuring cardiac Troponin I

NARCIS (Netherlands)

Kemper, D.W.; Semjonow, V.; de Theije, F.; Keizer, D.; van Lippen, L.; Mair, J.; Wille, B.; Christ, M.; Geijer, F.; Hausfater, P.; Pariente, D.; Scharnhorst, V.; Curvers, J.; Nieuwenhuis, J.

2017-01-01

OBJECTIVES: Point-of-care cardiac troponin testing with adequate analytical performances has the potential to improve chest pain patients flow in the emergency department. We present the analytical evaluation of the newly developed Philips Minicare cTnI point-of-care immunoassay. DESIGN & METHODS:

Restricted N-terminal truncation of cardiac troponin T: a novel mechanism for functional adaptation to energetic crisis.

Science.gov (United States)

Feng, Han-Zhong; Biesiadecki, Brandon J; Yu, Zhi-Bin; Hossain, M Moazzem; Jin, J-P

2008-07-15

The N-terminal variable region of cardiac troponin T (TnT) is a regulatory structure that can be selectively removed during myocardial ischaemia reperfusion by mu-calpain proteolysis. Here we investigated the pathophysiological significance of this post-translational modification that removes amino acids 1-71 of cardiac TnT. Working heart preparations were employed to study rat acute myocardial infarction and transgenic mouse hearts over-expressing the N-terminal truncated cardiac TnT (cTnT-ND). Ex vivo myocardial infarction by ligation of the left anterior descending coronary artery induced heart failure and produced cTnT-ND not only in the infarct but also in remote zones, including the right ventricular free wall, indicating a whole organ response in the absence of systemic neurohumoral mechanisms. Left ventricular pressure overload in mouse working hearts produced increased cTnT-ND in both ventricles, suggesting a role of haemodynamic stress in triggering an acute whole organ proteolytic regulation. Transgenic mouse hearts in which the endogenous intact cardiac TnT was partially replaced by cTnT-ND showed lowered contractile velocity. When afterload increased from 55 mmHg to 90 mmHg, stroke volume decreased in the wild type but not in the transgenic mouse hearts. Correspondingly, the left ventricular rapid-ejection time of the transgenic mouse hearts was significantly longer than that of wild type hearts, especially at high afterload. The restricted deletion of the N-terminal variable region of cardiac troponin T demonstrates a novel mechanism by which the thin filament regulation adapts to sustain cardiac function under stress conditions.

Cardiac complications in diphtheria and predictors of outcomes.

Science.gov (United States)

Samdani, Sunil; Jain, Avani; Meena, Vinod; Meena, C B

2018-01-01

To study the cardiac complications in diphtheria patients and to study the predictors of outcomes. Single centre prospective analysis of cardiac complications in diphtheria patients. In this study, there were 60 patients diagnosed with diphtheria with ECG changes. The ECG changes seen were sinus tachycardia (68.3%), T wave inversion (20%), ST segment depression (13.3%), right bundle branch block (5%), multiple atrial ectopics (3.3%). The case fatality rate in our study was 25% (15 patients). High CPK-MB, myoglobulin and cardiac troponin levels were associated with cardiac mortality. In our study, cardiac troponin T had the highest sensitivity (80%) and CK-MB had the highest specificity (95.56%). Cardiac involvement is a common complication of infection with C. diphtheria and is associated with high mortality. As diphtheria can be prevented by adequate vaccination, efforts should be maximized for high vaccine coverage with booster doses. Copyright © 2017. Published by Elsevier B.V.

Clinical Characteristics and Outcomes of Patients with Myocardial Infarction, Myocardial Injury, and Nonelevated Troponins

DEFF Research Database (Denmark)

Sarkisian, Laura; Saaby, Lotte; Poulsen, Tina S

2016-01-01

BACKGROUND: Cardiac troponins have emerged as the preferred biomarkers for detecting myocardial necrosis and diagnosing myocardial infarction. However, current cardiac troponin assays do not discriminate between ischemic and nonischemic causes of myocardial cell death. Thus, when an increased...... troponin value is encountered in the absence of obvious myocardial ischemia, a careful search for other clinical conditions is crucial. METHODS: In 2010 to 2011, we prospectively studied hospitalized patients who had cardiac troponin I measured on clinical indication. An acute myocardial infarction...... was diagnosed in cases of a cardiac troponin I increase or decrease pattern with at least 1 value >30 ng/L (99th percentile) together with myocardial ischemia. Myocardial injury was defined as cardiac troponin I values >30 ng/L, but without signs or symptoms indicating overt cardiac ischemia. Patients with peak...

Elevated Plasma Cardiac Troponin T Levels Caused by Skeletal Muscle Damage in Pompe Disease.

Science.gov (United States)

Wens, Stephan C A; Schaaf, Gerben J; Michels, Michelle; Kruijshaar, Michelle E; van Gestel, Tom J M; In 't Groen, Stijn; Pijnenburg, Joon; Dekkers, Dick H W; Demmers, Jeroen A A; Verdijk, Lex B; Brusse, Esther; van Schaik, Ron H N; van der Ploeg, Ans T; van Doorn, Pieter A; Pijnappel, W W M Pim

2016-02-01

Elevated plasma cardiac troponin T (cTnT) levels in patients with neuromuscular disorders may erroneously lead to the diagnosis of acute myocardial infarction or myocardial injury. In 122 patients with Pompe disease, the relationship between cTnT, cardiac troponin I, creatine kinase (CK), CK-myocardial band levels, and skeletal muscle damage was assessed. ECG and echocardiography were used to evaluate possible cardiac disease. Patients were divided into classic infantile, childhood-onset, and adult-onset patients. cTnT levels were elevated in 82% of patients (median 27 ng/L, normal values normal in all patients, whereas CK-myocardial band levels were increased in 59% of patients. cTnT levels correlated with CK levels in all 3 subgroups (Pmass index measured with echocardiography was normal in all the 3 subgroups. cTnT mRNA expression in skeletal muscle was not detectable in controls but was strongly induced in patients with Pompe disease. cTnT protein was identified by mass spectrometry in patient-derived skeletal muscle tissue. Elevated plasma cTnT levels in patients with Pompe disease are associated with skeletal muscle damage, rather than acute myocardial injury. Increased cTnT levels in Pompe disease and likely other neuromuscular disorders should be interpreted with caution to avoid unnecessary cardiac interventions. © 2016 American Heart Association, Inc.

Cardiac troponin T: A sensitive and specific indicator of myocardial injury in patients with cerebrovascular stroke

Directory of Open Access Journals (Sweden)

Mohammed Amin

2012-09-01

Conclusions: Myocardial injury is not uncommon in patients with CVS. Silent ST-T wave changes and new resting SWMA are possible complications. We demonstrated highly significant correlation between positive troponin T and myocardial injury in these patients.

Troponin T or troponin I or CK-MB (or none?).

Science.gov (United States)

Collinson, P O

1998-11-01

patients, thrombolysis is the treatment of choice. Patients presenting with ST segment elevation represents the minority of patients with probable ACS 9.6% of all patients presenting to our hospital. The majority require risk stratification into high- and low-risk groups. It is here that cardiac troponins have a major role. The measurement of cTnT has been shown in a large number of studies to enable risk stratification of patients with unstable angina. The combination of cTnT, admission ECG and stress ECG can be used for a comprehensive risk stratification of patients with unstable angina. The combination of cTnT, admission ECG and stress ECG can be used for a comprehensive risk stratification which can be completed by 24 h from admission, as well as allowing a safe discharge policy from the ED. Measurements of cardiac troponins can also be used to predict prognosis in patients with other diagnostic categories. Patients with cardiac failure can be risk stratified according to cTnT status. cTnT status on admission allows subdivision into high- and low-risk groups in patients presenting with ST segment elevation. Certainly, cTnT measurement can be incorporated into a clinical decision-making strategy to assign patients to investigation and management pathways. There is evidence that cTnT may be useful to guide therapeutic options. The major issue is one of cost. In the U.K. model of managed care with undemanding diagnostic standards, the role of cTnT will be to enhance clinical decision-making strategies, to provide accurate diagnosis and to reduce lengths of stay. This can be shown to have potential for major improvements in cost efficiency. Improvements in diagnostic accuracy can reduce inappropriate long-term drug therapy. In systems with a more aggressive laboratory investigation strategy, rationalization of test numbers will provide an immediate cost reduction while improving quality. Finally, use of point-of-care testing (POCT) means that biochemical testing can be pe

Risk prediction in stable cardiovascular disease using a high-sensitivity cardiac troponin T single biomarker strategy compared to the ESC-SCORE.

Science.gov (United States)

Biener, Moritz; Giannitsis, Evangelos; Kuhner, Manuel; Zelniker, Thomas; Mueller-Hennessen, Matthias; Vafaie, Mehrshad; Stoyanov, Kiril M; Neumann, Franz-Josef; Katus, Hugo A; Hochholzer, Willibald; Valina, Christian Marc

2018-01-01

To evaluate the prognostic performance of high-sensitivity cardiac troponin T (hs-cTnT) compared with the ESC-SCORE. We included low-risk outpatients with stable cardiovascular (CV) disease categorised into need for non-secondary and secondary prevention. The prognostication of hs-cTnT at index visit was compared with the European Society of Cardiology-Systematic COronary Risk Evaluation (ESC-SCORE) with respect to all-cause mortality (ACM) and two composite endpoints (ACM, acute myocardial infarction (AMI) and stroke and ACM, AMI, stroke and rehospitalisation for acute coronary syndrome (ACS) and decompensated heart failure (DHF)). Within a median follow-up of 796 days, a total of 16 deaths, 32 composite endpoints of ACM, AMI and stroke and 83 composite endpoints of ACM, AMI, stroke, rehospitalisation for ACS and DHF were observed among 693 stable low-risk outpatients. Using C-statistics, measurement of hs-cTnT alone outperformed the ESC-SCORE for the prediction of ACM in the entire study population (Δarea under the curve (AUC) 0.221, p=0.0039) and both prevention groups (non-secondary: ΔAUC 0.164, p=0.0208; secondary: ΔAUC 0.264, p=0.0134). For the prediction of all other secondary endpoints, hs-cTnT was at least as effective as the ESC-SCORE, both in secondary and non-secondary prevention. Using continuous and categorical net reclassification improvement and integrated discrimination improvement, hs-cTnT significantly improved reclassification regarding all endpoints in the entire population and in the secondary prevention cohort. In non-secondary prevention, hs-cTnT improved reclassification only for ACM. The results were confirmed in an independent external cohort on 2046 patients. Hs-cTnT is superior to the multivariable ESC-SCORE for the prediction of ACM and a composite endpoint in stable outpatients with and without relevant CV disease. NCT01954303; Pre-results.

Diagnosis of Unstable Angina Pectoris Has Declined Markedly with the Advent of More Sensitive Troponin Assays

DEFF Research Database (Denmark)

D'Souza, Maria; Sarkisian, Laura; Saaby, Lotte

2015-01-01

]) was established in cases of a rise and/or fall of cardiac troponin I together with cardiac ischemic features. Patients with unstable chest discomfort and cardiac troponin I values below the decision limit of myocardial infarction were diagnosed as having unstable angina pectoris. The definition of acute coronary...... syndrome included unstable angina pectoris, NSTEMI, and STEMI. Mortality data were obtained from the Danish Civil Personal Registration System. RESULTS: Of 3762 consecutive patients, 516 had acute coronary syndrome. Unstable angina pectoris was present in 7%, NSTEMI in 67%, and STEMI in 26%. The NSTEMI...... patients were older, more frequently women, and had more comorbidities than patients with unstable angina pectoris and STEMI. At median follow-up of 3.2 years 195 patients had died: 14% of unstable angina pectoris, 45% of NSTEMI, and 25% of STEMI patients. Age-adjusted log-rank statistics revealed...

Incidence of major vascular events after cardiac surgery: impact of preoperative monitoring with troponin and electrocardiogram

International Nuclear Information System (INIS)

Sandra M Quiroga; Juan C Villar; Luz X, Martinez

2009-01-01

Recent demographic changes have led to an increased risk of major vascular events among patients undergoing non-cardiac surgery. Troponin and electrocardiogram monitoring would further identify these major vascular events. Methods: we prospectively collected data on eligible patients (non-selected individuals aged 45 or older undergoing non-cardiac surgery under general or regional anesthesia in two hospitals in Bucaramanga, with expected length of stay longer than 24 hours) during a time-interrupted series,before and after postoperative diagnostic monitoring (blinded assessment of troponin T and electrocardiograms ignoring clinical data). For the period before the intervention (usual clinical care),two independent reviewers extracted clinical information from clinical histories (of all eligible patients from 3 randomly-selected months of 2005). For the period after diagnostic monitoring, we followed 100 consecutive eligible patients. Primary outcome was a composite of major vascular events within hospital, including myocardial infarction (defined as any troponin elevation associated with electrocardiographic changes suggesting ischemia, regardless of symptoms). Results: we included 534 clinical charts and 100 prospective surgical patients (mean age 62.2, SD 12.9 years; 56% women). The more frequent surgical procedures were orthopedics (26.8%) followed by abdominal (20.2%).The incidence of major vascular events recorded in clinical charts was 2.8%, compared with 7% among monitored patients (p=0,071). All four myocardial infarctions identified among the later group were silent. Conclusion: postoperative monitoring with troponin and electrocardiography identified a higher proportion of major vascular events, mainly silent myocardial infarctions.

High-NaCl Diet Aggravates Cardiac Injury in Rats with Adenine-Induced Chronic Renal Failure and Increases Serum Troponin T Levels

DEFF Research Database (Denmark)

Kashioulis, Pavlos; Hammarsten, Ola; Marcussen, Niels

2016-01-01

AIMS: To examine the effects of 2 weeks of high-NaCl diet on left ventricular (LV) morphology and serum levels of cardiac troponin T (cTnT) in rats with adenine-induced chronic renal failure (ACRF). METHODS: Male Sprague-Dawley rats either received chow containing adenine or were pair......-fed an identical diet without adenine [controls (C)]. Approximately 10 weeks after the beginning of the study, the rats were randomized to either remain on a normal NaCl diet (NNa; 0.6%) or to be switched to high-NaCl chow (HNa; 4%) for 2 weeks, after which acute experiments were performed. RESULTS: Rats with ACRF...... showed statistically significant increases (p rats (p

The relationship of plasma creatinine (as eGFR) and high-sensitivity cardiac troponin and NT-proBNP concentrations in a hospital and community outpatient population.

Science.gov (United States)

Potter, Julia M; Simpson, Aaron J; Kerrigan, Jennifer; Southcott, Emma; Salib, Marie M; Koerbin, Gus; Hickman, Peter E

2017-10-01

While persons with overt renal failure have a well-described rise in troponin and NT-proBNP, it is less well described what the relationship is between cardiac markers and persons with impaired renal function, not requiring dialysis. We have collected ALL samples referred to our pathology practice over a 24h period and measured hs-cTnI, hs-cTnT, NT-proBNP, calculated the eGFR, and related our measurements to clinical outcomes. For both men and women, for all of hs-cTnI, hs-cTnT and NT-proBNP, there was a graded response, as renal function worsened, the concentration of the cardiac marker increased. There is a graded inverse relationship between eGFR and the concentrations of hs-cTnI, hs-cTnT and NT-proBNP. For women only there appeared to be an increase in mortality at lowest eGFR. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Detected troponin elevation is associated with high early mortality after lung resection for cancer

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Van Tornout Fillip

2006-10-01

Full Text Available Abstract Background Myocardial infarction can be difficult to diagnose after lung surgery. As recent diagnostic criteria emphasize serum cardiac markers (in particular serum troponin we set out to evaluate its clinical utility and to establish the long term prognostic impact of detected abnormal postoperative troponin levels after lung resection. Methods We studied a historic cohort of patients with primary lung cancer who underwent intended surgical resection. Patients were grouped according to known postoperative troponin status and survival calculated by Kaplan Meier method and compared using log rank. Parametric survival analysis was used to ascertain independent predictors of mortality. Results From 2001 to 2004, a total of 207 patients underwent lung resection for primary lung cancer of which 14 (7% were identified with elevated serum troponin levels within 30 days of surgery, with 9 (64% having classical features of myocardial infarction. The median time to follow up (interquartile range was 22 (1 to 52 months, and the one and five year survival probabilities (95% CI for patients without and with postoperative troponin elevation were 92% (85 to 96 versus 60% (31 to 80 and 61% (51 to 71 versus 18% (3 to 43 respectively (p T stage and postoperative troponin elevation remained independent predictors of mortality in the final multivariable model. The acceleration factor for death of elevated serum troponin after adjusting for tumour stage was 9.19 (95% CI 3.75 to 22.54. Conclusion Patients with detected serum troponin elevation are at high risk of early mortality with or without symptoms of myocardial infarction after lung resection.

Fluorescent Protein-Based Ca2+ Sensor Reveals Global, Divalent Cation-Dependent Conformational Changes in Cardiac Troponin C.

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Myriam A Badr

Full Text Available Cardiac troponin C (cTnC is a key effector in cardiac muscle excitation-contraction coupling as the Ca2+ sensing subunit responsible for controlling contraction. In this study, we generated several FRET sensors for divalent cations based on cTnC flanked by a donor fluorescent protein (CFP and an acceptor fluorescent protein (YFP. The sensors report Ca2+ and Mg2+ binding, and relay global structural information about the structural relationship between cTnC's N- and C-domains. The sensors were first characterized using end point titrations to decipher the response to Ca2+ binding in the presence or absence of Mg2+. The sensor that exhibited the largest responses in end point titrations, CTV-TnC, (Cerulean, TnC, and Venus was characterized more extensively. Most of the divalent cation-dependent FRET signal originates from the high affinity C-terminal EF hands. CTV-TnC reconstitutes into skinned fiber preparations indicating proper assembly of troponin complex, with only ~0.2 pCa unit rightward shift of Ca2+-sensitive force development compared to WT-cTnC. Affinity of CTV-TnC for divalent cations is in agreement with known values for WT-cTnC. Analytical ultracentrifugation indicates that CTV-TnC undergoes compaction as divalent cations bind. C-terminal sites induce ion-specific (Ca2+ versus Mg2+ conformational changes in cTnC. Our data also provide support for the presence of additional, non-EF-hand sites on cTnC for Mg2+ binding. In conclusion, we successfully generated a novel FRET-Ca2+ sensor based on full length cTnC with a variety of cellular applications. Our sensor reveals global structural information about cTnC upon divalent cation binding.

Cardiac biomarkers in neonatology: BNP/NTproBNP, troponin I/T, CK-MB and myoglobin – a systematic review

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Rita P. Teixeira

2017-06-01

Full Text Available Cardiac biomarkers play a central role in myocardial injury and heart failure in adult patients, but their clinical relevance in neonatology has not been clearly stablished. The aim of this systematic review was to evaluate the recent literature on B-type natriuretic peptide (BNP/N-terminal-pro-BNP (NTproBNP, troponin I/T, Creatine Kinase-MB (CK-MB and myoglobin and their relationship with different pathologies of the newborn. A total of 67 articles were included to undergo data extraction, after a first text and abstract analysis and a second full-text analysis, using the PubMed database.Evidence shows that cardiac biomarkers are a useful and fast diagnostic tool with great potential for becoming as important as clinical and echocardiographic findings in pathologies of the heart. BNP/NTproBNP and troponin I/T demonstrated to be the ones with greater value. BNP/NTproBNP is of particular significance in the diagnosis and management of patent ductus arteriosus, as it has a good correlation with diagnosis, treatment and prognosis. Troponin T may be a beneficial additional marker for this disease, correlating with ductal significance and treatment response. Moreover, BNP/NTproBNP can be used, with other clinical and laboratory findings, in the diagnosis and as a guide for treatment in pulmonary hypertension and in the diagnosis and management of cardiac sequela in bronchopulmonary dysplasia. Troponin I/T finds its clinical importance in perinatal asphyxia as a marker of myocardial injury and a reliable indicator of severity and mortality. Further studies with larger cohort populations are needed for stablishing the cutoff values specific for each neonatal pathology allowing its early and proper management.

24-Hour Kinetics of Cardiac Troponin-T Using a "High-Sensitivity" Assay in Thoroughbred Chuckwagon Racing Geldings after Race and Associated Clinical Sampling Guidelines.

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Shields, E; Seiden-Long, I; Massie, S; Leguillette, R

2018-01-01

A "high-sensitivity" cardiac troponin-T (hscTnT) assay recently has been validated for use in horses and is a specific biomarker of myocardial damage. Postexercise release kinetics of cTnT utilizing the hscTnT assay have yet to be established in horses. To determine: (1) cTnT release kinetics in racing Thoroughbreds after a high-intensity 5/8th mile Chuckwagon race; (2) the effects of age on pre- and postrace cTnT concentrations; and (3) sampling guidelines for clinicians evaluating horses presenting after exercise. Samples were obtained from 38 Thoroughbred geldings aged 5-16 years before racing and immediately, 2, 3, 4, 6, 12, and 24 hour postrace. Prospective, observational study with convenience sampling. A fifth-generation hscTnT assay was used for plasma sample analysis, and concentrations were compared at all time-points. Correlations were determined between cTnT concentrations and age. Biochemistry analysis was performed to assess rhabdomyolysis, renal failure, and exercise-induced dehydration. All horses with measureable cTnT concentrations had significant postexercise increases in cTnT with a median peak (8.0 ng/L) at 3-hour postrace. All horses had peak postexercise cTnT concentrations 2- to 6-hour postrace ≤ the 99th percentile upper reference limit of 23.2 ng/L, after which all cTnT concentrations decreased until returning to baseline by 12-24 hours. There was no correlation over time between cTnT concentrations and age. In racing Thoroughbreds completing short-duration, high-intensity Chuckwagon races, cTnT concentrations are expected to be increased 2- to 6-hour postrace and to decrease by 12-24 hours while remaining ≤23.2 ng/L throughout. This study contributes to establishing guidelines for clinical use of the hscTnT assay in exercising horses. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Subclinical Atherosclerosis, Cardiac and Kidney Function, Heart Failure, and Dementia in the Very Elderly.

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Kuller, Lewis H; Lopez, Oscar L; Gottdiener, John S; Kitzman, Dalane W; Becker, James T; Chang, Yuefang; Newman, Anne B

2017-07-22

Heart failure (HF) and dementia are major causes of disability and death among older individuals. Risk factors and biomarkers of HF may be determinants of dementia in the elderly. We evaluated the relationship between biomarkers of cardiovascular disease and HF and risk of dementia and death. Three hypotheses were tested: (1) higher levels of high-sensitivity cardiac troponin T, N-terminal of prohormone brain natriuretic peptide, and cystatin C predict risk of death, cardiovascular disease, HF, and dementia; (2) higher levels of cardiovascular disease biomarkers are associated with increased risk of HF and then secondary increased risk of dementia; and (3) risk of dementia is lower among participants with a combination of lower coronary artery calcium, atherosclerosis, and lower high-sensitivity cardiac troponin T (myocardial injury). The Cardiovascular Health Study Cognition Study was a continuation of the Cardiovascular Health Study limited to the Pittsburgh, PA, center from 1998-1999 to 2014. In 1992-1994, 924 participants underwent magnetic resonance imaging of the brain. There were 199 deaths and 116 developed dementia before 1998-1999. Of the 609 participants eligible for the Pittsburgh Cardiovascular Health Study Cognition Study, 87.5% (n=532) were included in the study. There were 120 incident HF cases and 72% had dementia. In 80 of 87, dementia preceded HF. A combination of low coronary artery calcium score and low high-sensitivity cardiac troponin T was significantly associated with reduced risk of dementia and HF. Most participants with HF had dementia but with onset before HF. Lower high-sensitivity cardiac troponin T and coronary artery calcium was associated with low risk of dementia based on a small number of events. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00005133. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Molecular basis of calcium-sensitizing and desensitizing mutations of the human cardiac troponin C regulatory domain: a multi-scale simulation study.

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Peter Michael Kekenes-Huskey

Full Text Available Troponin C (TnC is implicated in the initiation of myocyte contraction via binding of cytosolic Ca²⁺ and subsequent recognition of the Troponin I switch peptide. Mutations of the cardiac TnC N-terminal regulatory domain have been shown to alter both calcium binding and myofilament force generation. We have performed molecular dynamics simulations of engineered TnC variants that increase or decrease Ca²⁺ sensitivity, in order to understand the structural basis of their impact on TnC function. We will use the distinction for mutants that are associated with increased Ca²⁺ affinity and for those mutants with reduced affinity. Our studies demonstrate that for GOF mutants V44Q and L48Q, the structure of the physiologically-active site II Ca²⁺ binding site in the Ca²⁺-free (apo state closely resembled the Ca²⁺-bound (holo state. In contrast, site II is very labile for LOF mutants E40A and V79Q in the apo form and bears little resemblance with the holo conformation. We hypothesize that these phenomena contribute to the increased association rate, k(on, for the GOF mutants relative to LOF. Furthermore, we observe significant positive and negative positional correlations between helices in the GOF holo mutants that are not found in the LOF mutants. We anticipate these correlations may contribute either directly to Ca²⁺ affinity or indirectly through TnI association. Our observations based on the structure and dynamics of mutant TnC provide rationale for binding trends observed in GOF and LOF mutants and will guide the development of inotropic drugs that target TnC.

TNNI3K is a novel mediator of myofilament function and phosphorylates cardiac troponin I

International Nuclear Information System (INIS)

Wang, Hui; Wang, Lin; Song, Li; Zhang, Yan-Wan; Ye, Jue; Xu, Rui-Xia; Shi, Na; Meng, Xian-Min

2013-01-01

The phosphorylation of cardiac troponin I (cTnI) plays an important role in the contractile dysfunction associated with heart failure. Human cardiac troponin I-interacting kinase (TNNI3K) is a novel cardiac-specific functional kinase that can bind to cTnI in a yeast two-hybrid screen. The purpose of this study was to investigate whether TNNI3K can phosphorylate cTnI at specific sites and to examine whether the phosphorylation of cTnI caused by TNNI3K can regulate cardiac myofilament contractile function. Co-immunoprecipitation was performed to confirm that TNNI3K could interact with cTnI. Kinase assays further indicated that TNNI3K did not phosphorylate cTnI at Ser23/24 and Ser44, but directly phosphorylated Ser43 and Thr143 in vitro. The results obtained for adult rat cardiomyocytes also indicated that enhanced phosphorylation of cTnI at Ser43 and Thr143 correlated with rTNNI3K (rat TNNI3K) overexpression, and phosphorylation was reduced when rTNNI3K was knocked down. To determine the contractile function modulated by TNNI3K-mediated phosphorylation of cTnI, cardiomyocyte contraction was studied in adult rat ventricular myocytes. The contraction of cardiomyocytes increased with rTNNI3K overexpression and decreased with rTNNI3K knockdown. We conclude that TNNI3K may be a novel mediator of cTnI phosphorylation and contribute to the regulation of cardiac myofilament contraction function

Impact of high-intensity interval training and moderate-intensity continuous training on resting and postexercise cardiac troponin T concentration.

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Nie, Jinlei; Zhang, Haifeng; Kong, Zhaowei; George, Keith; Little, Jonathan P; Tong, Tomas K; Li, Feifei; Shi, Qingde

2018-03-01

What is the central question of this study? Does exercise training impact resting and postexercise cardiac troponin T (cTnT) concentration? What is the main finding and its importance? This randomized controlled intervention study demonstrated that 12 weeks of either high-intensity interval training or moderate-intensity continuous training largely abolished the exercise-induced elevation in cTnT when exercise was performed at the same absolute intensity. There was no impact of training on resting cTnT or postexercise appearance of cTnT when exercise was performed at the same relative intensity. These findings provide new information that might help clinicians with decision-making in relationship to basal and postexercise values of cTnT in individuals with different training status. We evaluated the influence of 12 weeks of high-intensity interval training [HIIT; repeated 4 min cycling at 90% of maximal oxygen uptake (V̇O2max) interspersed with 3 min rest, 200-300 kJ per session, 3 or 4 days each week] and work-equivalent moderate-intensity continuous training (MICT; continuous cycling at 60% V̇O2max) on resting cardiac troponin T (cTnT) and the appearance of exercise-induced cTnT. Forty-eight sedentary obese young women were randomly assigned to HIIT, MICT or a control group. The V̇O2max and body composition were measured before and after training. At baseline, cTnT was assessed using a high-sensitivity assay at rest and immediately, 2 and 4 h after 45 min cycling at 60% V̇O2max. After a 12 week training period, cTnT was assessed before and after 45 min cycling at the same relative and absolute intensities as before training. Training led to higher V̇O2max and lower fat mass in both HIIT and MICT groups (all P training, cTnT was significantly elevated in all three groups (by 35-118%, all P training, both resting and postexercise cTnT concentrations (same relative intensity) were similar to pretraining values. In contrast, postexercise cTnT (same

The impact of intermittent exercise in a hypoxic environment on redox status and cardiac troponin release in the serum of well-trained marathon runners.

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Li, Feifei; Nie, Jinlei; Lu, Yifan; Tong, Tom Kwok Keung; Yi, Longyan; Yan, Huiping; Fu, Frank Hoo Kin; Ma, Shengxia

2016-10-01

To investigate the effects of hypoxic training on redox status and cardiac troponin (cTn) release after intermittent exercise. Nine well-trained male marathon runners (age, 21.7 ± 2.3 year; body mass, 64.7 ± 4.8 kg; height, 177.9 ± 3.8 cm; and VO2max, 64.3 ± 6.7 ml kg(-1) min(-1)) completed intermittent exercise under normoxic [trial N; fraction of inspiration oxygen (FIO2), 21.0 %] and hypoxic (trial H; FIO2, 14.4 %) conditions in random order. Each bout of intermittent exercise included hard run (16.2 ± 0.8 km h(-1)) at 90 % VO2max for 2 min followed by easy run (9.0 ± 0.4 km h(-1)) at 50 % VO2max for 2 min and 23 bouts in 92 min totally. Malondialdehyde, reduced glutathione (GSH), superoxide dismutase, an estimate of total antioxidant capacity (T-AOC), high-sensitivity cardiac troponin T (hs-cTnT), and cardiac troponin I (cTnI) were measured before, immediately after (0 h), and 2, 4, and 24 h after the completion of trials N and H. GSH was increased immediately after trial N. T-AOC was lower 4 h after trial H than trial N. Hs-cTnT was elevated from 0 to 4 h and returned to baseline 24 h after both trials. CTnI was increased after trial H; peaked at 2-4 h and returned to below the detection by 24 h. The overall redox status was balanced under normoxic conditions, and exercise-induced cTn release did not deviate. However, the protective effects of antioxidant were weaker in the hypoxic state than normoxic, and the stress on the myocardium induced by intermittent exercise was transiently aggravated.

Ca2+-induced PRE-NMR changes in the troponin complex reveal the possessive nature of the cardiac isoform for its regulatory switch.

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Nicole M Cordina

Full Text Available The interaction between myosin and actin in cardiac muscle, modulated by the calcium (Ca2+ sensor Troponin complex (Tn, is a complex process which is yet to be fully resolved at the molecular level. Our understanding of how the binding of Ca2+ triggers conformational changes within Tn that are subsequently propagated through the contractile apparatus to initiate muscle activation is hampered by a lack of an atomic structure for the Ca2+-free state of the cardiac isoform. We have used paramagnetic relaxation enhancement (PRE-NMR to obtain a description of the Ca2+-free state of cardiac Tn by describing the movement of key regions of the troponin I (cTnI subunit upon the release of Ca2+ from Troponin C (cTnC. Site-directed spin-labeling was used to position paramagnetic spin labels in cTnI and the changes in the interaction between cTnI and cTnC subunits were then mapped by PRE-NMR. The functionally important regions of cTnI targeted in this study included the cTnC-binding N-region (cTnI57, the inhibitory region (cTnI143, and two sites on the regulatory switch region (cTnI151 and cTnI159. Comparison of 1H-15N-TROSY spectra of Ca2+-bound and free states for the spin labeled cTnC-cTnI binary constructs demonstrated the release and modest movement of the cTnI switch region (∼10 Å away from the hydrophobic N-lobe of troponin C (cTnC upon the removal of Ca2+. Our data supports a model where the non-bound regulatory switch region of cTnI is highly flexible in the absence of Ca2+ but remains in close vicinity to cTnC. We speculate that the close proximity of TnI to TnC in the cardiac complex is favourable for increasing the frequency of collisions between the N-lobe of cTnC and the regulatory switch region, counterbalancing the reduction in collision probability that results from the incomplete opening of the N-lobe of TnC that is unique to the cardiac isoform.

Can we monitor heart attack in the troponin era: evidence from a population-based cohort study

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Rankin Jamie M

2011-06-01

Full Text Available Abstract Background Troponins (highly sensitive biomarkers of myocardial damage increase counts of myocardial infarction (MI in clinical practice, but their impact on trends in admission rates for MI in National statistics is uncertain. Methods Cases coded as MI or other cardiac diagnoses in the Hospital Morbidity Data Collection (MI-HMDC in Western Australia in 1998 and 2003 were classified using revised criteria for MI developed by an International panel convened by the American Heart Association (AHA criteria using information on symptoms, ECGs and cardiac biomarkers abstracted from samples of medical notes. Age-sex standardized rates of MI-HMDC were compared with rates of MI based on AHA criteria including troponins (MI-AHA or traditional biomarkers only (MI-AHAck. Results Between 1998 and 2003, rates of MI-HMDC decreased by 3.5% whereas rates of MI-AHA increased by 17%, a difference largely due to increased false-negative cases in the HMDC associated with marked increased use of troponin tests in cardiac admissions generally, and progressively lower test thresholds. In contrast, rates of MI-AHAck declined by 18%. Conclusions Increasing misclassification of MI-AHA by the HMDC may be due to reluctance by clinicians to diagnose MI based on relatively small increases in troponin levels. These influences are likely to continue. Monitoring MI using AHA criteria will require calibration of commercially available troponin tests and agreement on lower diagnostic thresholds for epidemiological studies. Declining rates of MI-AHAck are consistent with long-standing trends in MI in Western Australia, suggesting that neither MI-HMDC nor MI-AHA reflect the true underlying population trends in MI.

MIPs-graphene nanoplatelets-MWCNTs modified glassy carbon electrode for the determination of cardiac troponin I.

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Ma, Ya; Shen, Xiao-Lei; Wang, Hai-Shui; Tao, Jia; Huang, Jian-Zhi; Zeng, Qiang; Wang, Li-Shi

2017-03-01

An electrochemical sensor with high selectivity in addition to sensitivity was developed for the determination of cardiac troponin I (cTnI), based on the modification of cTnI imprinted polymer film on a glassy carbon electrode (GCE). The sensor was fabricated by layer-by-layer assembled graphene nanoplatelets (GS), multiwalled carbon nanotubes (MWCNTs), chitosan (CS), glutaraldehyde (GA) composites, which can increase the electronic transfer rate and the active surface area to capture a larger number of antigenic proteins. MWCNTs/GS based imprinted polymers (MIPs/MWCNTs/GS) were synthesized by means of methacrylic acid (MAA) as the monomer, ethylene glycol dimethacrylate (EGDMA) as the cross linker α,α'-azobisisobutyronitrile (AIBN) as the initiator and cTnI as the template. In comparison with conventional methods, the proposed electrochemical sensor is highly sensitive for cTnI, providing a better linear response range from 0.005 to 60 ng cm -3 and a lower limit of detection (LOD) of 0.0008 ng cm -3 under optimal experimental conditions. In addition, the electrochemical sensor exhibited good specificity, acceptable reproducibility and stability. Moreover, satisfactory results were obtained in real human serum samples, indicating that the developed method has the potential to find application in clinical detection of cTnI as an alternative approach. Copyright © 2016 Elsevier Inc. All rights reserved.

Cardiac biomarkers in neonatal hypoxic ischaemia.

LENUS (Irish Health Repository)

Sweetman, D

2012-04-01

Following a perinatal hypoxic-ischaemic insult, term infants commonly develop cardiovascular dysfunction. Troponin-T, troponin-I and brain natriuretic peptide are sensitive indicators of myocardial compromise. The long-term effects of cardiovascular dysfunction on neurodevelopmental outcome following perinatal hypoxic ischaemia remain controversial. Follow-up studies are warranted to ensure optimal cardiac function in adulthood. CONCLUSION: Cardiac biomarkers may improve the diagnosis of myocardial injury, help guide management, estimate mortality risk and may also aid in longterm neurodevelopmental outcome prediction following neonatal hypoxic-ischaemia.

External validation of heart-type fatty acid binding protein, high-sensitivity cardiac troponin, and electrocardiography as rule-out for acute myocardial infarction.

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Van Hise, Christopher B; Greenslade, Jaimi H; Parsonage, William; Than, Martin; Young, Joanna; Cullen, Louise

2018-02-01

To externally validate a clinical decision rule incorporating heart fatty acid binding protein (h-FABP), high-sensitivity troponin (hs-cTn) and electrocardiogram (ECG) for the detection of acute myocardial infarction (AMI) on presentation to the Emergency Department. We also investigated whether this clinical decision rule improved identification of AMI over algorithms incorporating hs-cTn and ECG only. This study included data from 789 patients from the Brisbane ADAPT cohort and 441 patients from the Christchurch TIMI RCT cohort. The primary outcome was index AMI. Sensitivity, specificity, positive predictive value and negative predictive value were used to assess the diagnostic accuracy of the algorithms. 1230 patients were recruited, including 112 (9.1%) with AMI. The algorithm including h-FABP and hs-cTnT had 100% sensitivity and 32.4% specificity. The algorithm utilising h-FABP and hs-cTnI had similar sensitivity (99.1%) and higher specificity (43.4%). The hs-cTnI and hs-cTnT algorithms without h-FABP both had a sensitivity of 98.2%; a result that was not significantly different from either algorithm incorporating h-FABP. Specificity was higher for the hs-cTnI algorithm (68.1%) compared to the hs-cTnT algorithm (33.0%). The specificity of the algorithm incorporating hs-cTnI alone was also significantly higher than both of the algorithms incorporating h-FABP (p<0.01). For patients presenting to the Emergency Department with chest pain, an algorithm incorporating h-FABP, hs-cTn and ECG has high accuracy and can rule out up to 40% of patients. An algorithm incorporating only hs-cTn and ECG has similar sensitivity and may rule out a higher proportion of patients. Each of the algorithms can be used to safely identify patients as low risk for AMI on presentation to the Emergency Department. Copyright © 2017 The Canadian Society of Clinical Chemists. All rights reserved.

Diagnosis of type 1 and type 2 myocardial infarction using a high-sensitivity cardiac troponin I assay with sex-specific 99th percentiles based on the third universal definition of myocardial infarction classification system.

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Sandoval, Yader; Smith, Stephen W; Schulz, Karen M; Murakami, MaryAnn M; Love, Sara A; Nicholson, Jennifer; Apple, Fred S

2015-04-01

The frequency and characteristics of myocardial infarction (MI) subtypes per the Third Universal Definition of MI (TUDMI) classification system using high-sensitivity (hs) cardiac troponin assays with sex-specific cutoffs is not well known. We sought to describe the diagnostic characteristics of type 1 (T1MI) and type 2 (T2MI) MI using an hs-cardiac troponin I (hs-cTnI) assay with sex-specific cutoffs. A total of 310 consecutive patients with serial cTnI measurements obtained on clinical indication were studied with contemporary and hs-cTnI assays. Ninety-ninth percentile sex-specific upper reference limits (URLs) for the hs-cTnI assay were 16 ng/L for females and 34 ng/L for males. The TUDMI consensus recommendations were used to define and adjudicate MI based on each URL. A total of 127 (41%) patients had at least 1 hs-cTnI exceeding the sex-specific 99th percentiles, whereas 183 (59%) had hs-cTnI within the reference interval. Females had more myocardial injury related to supply/demand ischemia than males (39% vs 18%, P = 0.01), whereas males had more multifactorial or indeterminate injury (52% vs 33%, P = 0.05). By hs-cTnI, there were 32 (10%) acute MIs, among which 10 (3%) were T1MI and 22 (7%) were T2MI. T2MI represented 69% (22 out of 32) of all acute MIs, whereas T1MI represented 31% (10 out of 32). Ninety-five patients (31%) had an increased hs-cTnI above the 99th percentile but did not meet criteria for acute MI. The most common triggers for T2MI were tachyarrhythmias, hypotension/shock, and hypertension. By contemporary cTnI, more MIs (14 T1MI and 29 T2MI) were diagnosed. By contemporary cTnI, there were 43 MIs, 14 T1MI, and 29 T2MI. Fewer MI diagnoses were found with the hs-cTnI assay, contrary to the commonly accepted idea that hs-cTnI will lead to excessive false-positive diagnoses. © 2015 American Association for Clinical Chemistry.

Cardiac involvement in canine babesiosis : review article

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R.G. Lobetti

2005-06-01

Full Text Available Cardiac dysfunction in canine babesiosis has traditionally been regarded as a rare complication, with the majority of lesions reported as incidental findings at post-mortem examination. Recent studies have, however, demonstrated cardiac lesions in canine babesiosis. Cardiac troponins, especially troponin I, are sensitive markers of myocardial injury in canine babesiosis, and the magnitude of elevation of plasma troponin I concentrations appears to be proportional to the severity of the disease. ECG changes in babesiosis are similar to the pattern described for myocarditis and myocardial ischaemia and together with histopathological findings indicate that the heart suffers from the same pathological processes described in other organs in canine babesiosis, namely inflammation and hypoxia. The clinical application of the ECG appears to be limited and thus cardiovascular assessment should be based on functional monitoring rather than an ECG tracing. On cardiac histopathology from dogs that succumbed to babesiosis, haemorrhage, necrosis, inflammation and fibrin microthrombi in the myocardium were documented, all of which would have resulted in ECG changes and elevations in cardiac troponin. Myocardial damage causes left ventricular failure, which will result in hypotension and an expansion of the plasma volume due to homeostatic mechanisms.

Characterization and validation of new tools for measuring site-specific cardiac troponin I phosphorylation.

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Thoemmes, Stephen F; Stutzke, Crystal A; Du, Yanmei; Browning, Michael D; Buttrick, Peter M; Walker, Lori A

2014-01-31

Phosphorylation of cardiac troponin I is a well established mechanism by which cardiac contractility is modulated. However, there are a number of phosphorylation sites on TnI which contribute singly or in combination to influence cardiac function. Accordingly, methods for accurately measuring site-specific TnI phosphorylation are needed. Currently, two strategies are employed: mass spectrometry, which is costly, difficult and has a low throughput; and Western blotting using phospho-specific antibodies, which is limited by the availability of reagents. In this report, we describe a cohort of new site-specific TnI phosphoantibodies, generated against physiologically relevant phosphorylation sites, that are superior to the current commercially available antibodies: to phospho-serine 22/23 which shows a >5-fold phospho-specificity for phosphorylated TnI; to phospho-serine 43, which has >3-fold phospho-specificity for phosphorylated TnI; and phospho-serine 150 which has >2-fold phospho-specificity for phosphorylated TnI. These new antibodies demonstrated greater sensitivity and specificity for the phosphorylated TnI than the most widely used commercially available reagents. For example, at a protein load of 20 μg of total cardiac extract, a commercially available antibody recognized both phosphorylated and dephosphorylated TnI to the same degree. At the same protein load our phospho-serine 22/23 antibody exhibited no cross-reactivity with dephosphorylated TnI. These new tools should allow a more accurate assessment and a better understanding of the role of TnI phosphorylation in the response of the heart to pathologic stress. Copyright © 2013 Elsevier B.V. All rights reserved.

Detection of high-sensitivity troponin in outpatients with stable pulmonary hypertension identifies a subgroup at higher risk of adverse outcomes.

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Roy, Andrew K; McCullagh, Brian N; Segurado, Ricardo; McGorrian, Catherine; Keane, Elizabeth; Keaney, John; Fitzgibbon, Maria N; Mahon, Niall G; Murray, Patrick T; Gaine, Sean P

2014-01-01

The detection of elevations in cardiorenal biomarkers, such as troponins, B-type natriuretic peptides (BNPs), and neutrophil gelatinase-associated lipocalins, are associated with poor outcomes in patients hospitalized with acute heart failure. Less is known about the association of these markers with adverse events in chronic right ventricular dysfunction due to pulmonary hypertension, or whether their measurement may improve risk assessment in the outpatient setting. We performed a cohort study of 108 patients attending the National Pulmonary Hypertension Unit in Dublin, Ireland, from 2007 to 2009. Cox proportional hazards analysis and receiver operating characteristic curves were used to determine predictors of mortality and hospitalization. Death or hospitalization occurred in 50 patients (46.3%) during the median study period of 4.1 years. Independent predictors of mortality were: 1) decreasing 6-minute walk test (6MWT; hazard ratio [HR] 12.8; P < .001); 2) BNP (HR 6.68; P < .001); and 3) highly sensitive troponin (hsTnT; HR 5.48; P < .001). Adjusted hazard analyses remained significant when hsTnT was added to a model with BNP and 6MWT (HR 9.26, 95% CI 3.61-23.79), as did the predictive ability of the model for death and rehospitalization (area under the receiver operating characteristic curve 0.81, 95% CI 0.73-0.90). Detection of troponin using a highly sensitive assay identifies a pulmonary hypertension subgroup with a poorer prognosis. hsTnT may also be used in a risk prediction model to identify patients at higher risk who may require escalation of targeted pulmonary vasodilator therapies and closer clinical surveillance. Copyright © 2014 Elsevier Inc. All rights reserved.

The Correlation between Troponin and Ferritin Serum Levels in the Patients with Major Beta-Thalassemia

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Iraj Shahramian

2013-06-01

Full Text Available Background: Thalassemia is a hereditary hemoglobinopathy whose most common complication is cardiac involvement which ends up in these patients’ death. Since troponin is a sensitive and specific marker for the detection of microinfarct, we studied the relationship between troponin and ferritin serum levels for early diagnosis of cardiac involvement in these patients. Materials and Methods: This case-control study was performed on 80 patients, including 40 patients with major thalassemia and normal echocardiography and 40 healthy volunteers ranging from 6 months to 16 years old. All the children were examined and the eligible children who were not infected with known heart disease, iron deficiency anemia, kidney disease, diabetes, fever, and systemic diseases were enrolled into the study after obtaining written informed consents from their parents. At 8:00 A.M. before breakfast, 5cc blood was drawn from these children. After collecting the samples, ferritin and troponin serum levels were evaluated using ELISA and electro- kymonolonsense methods, respectively. The gathered data were analyzed through the SPSS statistical software (v. 20 and T-test. Besides, P value<0.05 was considered as statistically significant. Results: The study results revealed a significant difference between the two groups regarding the mean of the serum levels of troponin (P=0.045 and ferritin (P=0.001. In this study, no significant correlation was observed between serum troponin and ferritin levels and age and BMI in the two groups. Also, no significant relationship was found between serum troponin level and sex (P=0.264. Conclusions: In microinfarct, troponin increases independent of ferritin; therefore, it can be used for early detection of cardiac involvement in thalassemia patients to determine the sub-clinical effects.

Effect of Xenon Anesthesia Compared to Sevoflurane and Total Intravenous Anesthesia for Coronary Artery Bypass Graft Surgery on Postoperative Cardiac Troponin Release: An International, Multicenter, Phase 3, Single-blinded, Randomized Noninferiority Trial.

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Hofland, Jan; Ouattara, Alexandre; Fellahi, Jean-Luc; Gruenewald, Matthias; Hazebroucq, Jean; Ecoffey, Claude; Joseph, Pierre; Heringlake, Matthias; Steib, Annick; Coburn, Mark; Amour, Julien; Rozec, Bertrand; Liefde, Inge de; Meybohm, Patrick; Preckel, Benedikt; Hanouz, Jean-Luc; Tritapepe, Luigi; Tonner, Peter; Benhaoua, Hamina; Roesner, Jan Patrick; Bein, Berthold; Hanouz, Luc; Tenbrinck, Rob; Bogers, Ad J J C; Mik, Bert G; Coiffic, Alain; Renner, Jochen; Steinfath, Markus; Francksen, Helga; Broch, Ole; Haneya, Assad; Schaller, Manuella; Guinet, Patrick; Daviet, Lauren; Brianchon, Corinne; Rosier, Sebastien; Lehot, Jean-Jacques; Paarmann, Hauke; Schön, Julika; Hanke, Thorsten; Ettel, Joachym; Olsson, Silke; Klotz, Stefan; Samet, Amir; Laurinenas, Giedrius; Thibaud, Adrien; Cristinar, Mircea; Collanges, Olivier; Levy, François; Rossaint, Rolf; Stevanovic, Ana; Schaelte, Gereon; Stoppe, Christian; Hamou, Nora Ait; Hariri, Sarah; Quessard, Astrid; Carillion, Aude; Morin, Hélène; Silleran, Jacqueline; Robert, David; Crouzet, Anne-Sophie; Zacharowski, Kai; Reyher, Christian; Iken, Sonja; Weber, Nina C; Hollmann, Marcus; Eberl, Susanne; Carriero, Giovanni; Collacchi, Daria; Di Persio, Alessandra; Fourcade, Olivier; Bergt, Stefan; Alms, Angela

2017-12-01

Ischemic myocardial damage accompanying coronary artery bypass graft surgery remains a clinical challenge. We investigated whether xenon anesthesia could limit myocardial damage in coronary artery bypass graft surgery patients, as has been reported for animal ischemia models. In 17 university hospitals in France, Germany, Italy, and The Netherlands, low-risk elective, on-pump coronary artery bypass graft surgery patients were randomized to receive xenon, sevoflurane, or propofol-based total intravenous anesthesia for anesthesia maintenance. The primary outcome was the cardiac troponin I concentration in the blood 24 h postsurgery. The noninferiority margin for the mean difference in cardiac troponin I release between the xenon and sevoflurane groups was less than 0.15 ng/ml. Secondary outcomes were the safety and feasibility of xenon anesthesia. The first patient included at each center received xenon anesthesia for practical reasons. For all other patients, anesthesia maintenance was randomized (intention-to-treat: n = 492; per-protocol/without major protocol deviation: n = 446). Median 24-h postoperative cardiac troponin I concentrations (ng/ml [interquartile range]) were 1.14 [0.76 to 2.10] with xenon, 1.30 [0.78 to 2.67] with sevoflurane, and 1.48 [0.94 to 2.78] with total intravenous anesthesia [per-protocol]). The mean difference in cardiac troponin I release between xenon and sevoflurane was -0.09 ng/ml (95% CI, -0.30 to 0.11; per-protocol: P = 0.02). Postoperative cardiac troponin I release was significantly less with xenon than with total intravenous anesthesia (intention-to-treat: P = 0.05; per-protocol: P = 0.02). Perioperative variables and postoperative outcomes were comparable across all groups, with no safety concerns. In postoperative cardiac troponin I release, xenon was noninferior to sevoflurane in low-risk, on-pump coronary artery bypass graft surgery patients. Only with xenon was cardiac troponin I release less than with total intravenous

Association of Elevated High Sensitivity Cardiac Troponin T(hs-cTnT) Levels with Hemorrhagic Transformation and 3-Month Mortality in Acute Ischemic Stroke Patients with Rheumatic Heart Disease in China.

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Liu, Junfeng; Wang, Deren; Xiong, Yao; Liu, Bian; Hao, Zilong; Tao, Wendan; Liu, Ming

2016-01-01

Elevated levels of high sensitivity cardiac troponin T (hs-cTnT) occur in a substantial proportion of patients with acute ischemic stroke (AIS) and can predict poor outcome and mortality after stroke. Whether elevated hs-cTnT levels can also predict hemorrhagic transformation (HT) or prognosis in AIS patients with rheumatic heart disease (RHD) remains unclear. Data from the Chengdu Stroke Registry on consecutive AIS patients with RHD admitted to West China Hospital within 1 month of stroke onset from October 2011 to February 2014 were examined. Clinico-demographic characteristics, HT, functional outcomes and stroke recurrence were compared between patients with elevated hs-cTnT levels (≥14 ng/L) and patients with normal hs-cTnT levels (mortality and 3-month disability/mortality (all P≤0.029). After controlling for age, sex, hypertension, renal impairment and National Institutes of Health Stroke Scale score on admission, the risk of HT and 3-month mortality was, respectively, 4.0- and 5.5-fold higher in patients with elevated hs-cTnT levels than in patients with normal hs-cTnT levels. Elevated hs-cTnT levels are independently associated with HT and 3-month mortality in AIS patients with RHD. These results with a small cohort should be verified and extended in large studies.

[Early detection of the cardiotoxicity induced by chemotherapy drug through two-dimensional speckle tracking echocardiography combined with high-sensitive cardiac troponin T].

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Wang, W; Kang, Y; Shu, X H; Shen, X D; He, B

2017-11-23

Objective: To investigate the clinical value of two-dimensional speckle tracking echocardiography(2D-STE) combined with high-sensitive cardiac troponin T (hs-cTnT) in early detection of the cardiotoxicity induced by chemotherapy drug. Methods: Seventy-five non-Hodgkin's lymphoma patients who received the CHOP regimen were recruited in this study. Conventional echocardiography and 2D-STE were performed on these patients before chemotherapy, the second day after the third course of chemotherapy (during chemotherapy) and the second day after the last course of chemotherapy (after chemotherapy). The parameters included left ventricular ejection fraction (LVEF), global longitudinal strain (LS), global circumferential strain (CS) and global radial strain (RS). The serum hs-cTNT levels were tested simultaneously. Results: Three cycles of CHOP were completed in 30 patients and 6-8 cycles of CHOP were completed in 45 patients. The LVEF of 75 patients before, during and after chemotherapy was (63.8±2.6)%, (63.8±2.8)% and (64.0±3.3)%, respectively, without significant difference ( P =0.91). However, the LS of 75 patients before, during and after chemotherapy was (-18.5±1.7)%, (-16.5±1.9)% and (-16.0±1.6)%, respectively. The CS was (-20.9±2.9)%, (-19.3±3.5)% and (-19.2±3.2)%, respectively. The RS was (39.2±6.4)%, (35.3±5.2)% and (35.0±6.2)%, respectively. The hs-cTnT was (0.001 0±0.002 0)ng/ml, (0.006 3±0.008 9)ng/ml and (0.007 3±0.003 8)ng/ml, respectively. The LS, CS and RS were significantly decreased while hs-cTnT was significantly increased during chemotherapy when compared to those before chemotherapy (all of P chemotherapy were marginally different from those during chemotherapy (all of P >0.05). Moreover, T(LS-SD), T(CS-SD) and T(RS-SD) showed no significant difference before, during and after chemotherapy (all of P >0.05). The reduction of LS was positively associated with the enhancement of hs-cTnT after chemotherapy ( r =0.60, P effectively and

Consequences of implementing a cardiac troponin assay with improved sensitivity at Swedish coronary care units: an analysis from the SWEDEHEART registry.

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Eggers, Kai M; Lindahl, Bertil; Melki, Dina; Jernberg, Tomas

2016-08-07

Cardiac troponin (cTn) assays with improved sensitivity are increasingly utilized for the assessment of patients admitted because of suspected acute coronary syndrome (ACS). However, data on the clinical consequences of the implementation of such assays are limited. In a retrospective register-based study (37 710 coronary care unit admissions; SWEDEHEART registry), we compared the case mix, the use of diagnostic procedures, treatments, and 1-year all-cause mortality 1 year before the implementation of a cTn assay with improved sensitivity (study period 1) and 1 year thereafter (study period 2). During study period 2, more at-risk patients were admitted and more patients had cTn levels above the myocardial infarction cut-off (ACS patients +13.1%; non-ACS patients +160.1%). cTn levels above this cut-off exhibited stronger associations with mortality risk in study period 2 (adjusted HR 4.45 [95% confidence interval, CI, 3.36-5.89]) compared with period 1 (adjusted HR 2.43 [95% CI 2.11-2.80]), similar as for the cTn ratio relative to the respective 99th percentile. While there was no multivariable-adjusted increase in the use of diagnostic procedures, significant trends towards more differentiated treatment depending on the cause of cTn elevation, i.e. ACS or non-ACS, were noted. The implementation of a cTn assay with improved sensitivity was associated with an increase in the number of patients who due to their cTn-status were identified as suitable for beneficial therapies. There was no inappropriate increase in hospital resource utilization. As such, cTn assays with improved sensitivity provide an opportunity to improve the clinical management of patients with suspected ACS. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Selection of specific inhibitor peptides in enzyme-linked immunosorbent assay (ELISA) of cardiac troponin I using immuno-dominant epitopes as competitor.

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Rezaee, Majid Asiabanha; Rasaee, Mohammad Javad; Mohammadnejad, Javad

2017-01-01

Human cardiac troponin I (cTni) is the gold marker for early diagnosis of myocardial infarction. In this regard, four immune-dominant epitopes of cTni were predicted and their 3D structures were determined. Thereafter, the competitive performance of the peptides was monitored with the developed polyclonal antibody-based indirect competitive ELISA; a half-maximal inhibitory concentration (IC50) of 0.49 (µg/mL) and detection limit of 0.037 (µg/mL) were achieved for recombinant cTni. The competitive ELISA determined sensitivity levels of 0.306, 0.141, 0.960, and 0.155 (µg/mL), respectively, for each peptide as competitor. We indicated that two of the selected epitopes have significant sensitivity scales and inhibition ability.

Validation, optimisation, and application data in support of the development of a targeted selected ion monitoring assay for degraded cardiac troponin T

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Alexander S. Streng

2016-06-01

Full Text Available Cardiac troponin T (cTnT fragmentation in human serum was investigated using a newly developed targeted selected ion monitoring assay, as described in the accompanying article: “Development of a targeted selected ion monitoring assay for the elucidation of protease induced structural changes in cardiac troponin T” [1]. This article presents data describing aspects of the validation and optimisation of this assay. The data consists of several figures, an excel file containing the results of a sequence identity search, and a description of the raw mass spectrometry (MS data files, deposited in the ProteomeXchange repository with id PRIDE: http://www.ebi.ac.uk/pride/archive/projects/PXD003187.

Cardiac troponin T and CK-MB mass release after visually successful percutaneous transluminal coronary angioplasty in stable angina pectoris

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Ravkilde, J; Nissen, H; Mickley, H

1994-01-01

The incidence of cardiac troponin T (Tn-T) and creatine kinase (CK) isoenzyme MB mass release was studied in 23 patients with stable angina pectoris undergoing visually successful percutaneous transluminal coronary angioplasty (PTCA). Serial blood samples were drawn for measurement of serum Tn...

A novel diagnostic protocol to identify patients suitable for discharge after a single high-sensitivity troponin

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Carlton, Edward W; Cullen, Louise; Than, Martin; Gamble, James; Khattab, Ahmed; Greaves, Kim

2015-01-01

Objective To establish whether a novel accelerated diagnostic protocol (ADP) for suspected acute coronary syndrome (ACS) could successfully identify low-risk patients suitable for discharge after a single high-sensitivity troponin T (hs-cTnT) taken at presentation to the emergency department. We also compared the diagnostic accuracy of this ADP with strategies using initial undetectable hs-cTnT. Methods This prospective observational study evaluated the ability of the Triage Rule-out Using high-Sensitivity Troponin (TRUST) ADP to identify low-risk patients with suspected ACS. The ADP incorporated a single presentation hs-cTnT of <14 ng/L, a non-ischaemic ECG and a modified Goldman risk score. Diagnostic performance of the ADP was compared with the detection limit cut-offs of hs-cTnT (<5 ng/L and <3 ng/L). The primary end point was fatal/non-fatal acute myocardial infarction (AMI) within 30 days. Results 960 participants were recruited, mean age 58.0 years, 80 (8.3%) had an AMI. The TRUST ADP classified 382 (39.8%) as low-risk with a sensitivity for identifying AMI of 98.8% (95% CI 92.5% to 99.9%). hs-cTnT detection limits (<5 ng/L and <3 ng/L) had a sensitivity of 100% (94.3 to 100) and 100% (94.4 to 100), respectively. The TRUST ADP identified more patients suitable for early discharge at 39.8% vs 29.3% (<5 ng/L) and 7.9% (<3 ng/L) (p<0.001) with a lower false-positive rate for AMI detection; specificity 43.3% (95% CI 42.7% to 43.4%) vs 32.0% (95% CI 31.5% to 32.0%) and 8.6% (95% CI 8.1% to 8.6%), respectively. Conclusions The TRUST ADP, which incorporates structured risk-assessment and a single presentation hs-cTnT blood draw, has potential to allow early discharge in 40% of patients with suspected ACS and has greater clinical utility than undetectable hs-cTnT strategies. Trial registration number ISRCTN No. 21109279. PMID:25691511

Sensitive Troponin I Assay in Patients with Chest Pain - Association with Significant Coronary Lesions with or Without Renal Failure.

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Soeiro, Alexandre de Matos; Gualandro, Danielle Menosi; Bossa, Aline Siqueira; Zullino, Cindel Nogueira; Biselli, Bruno; Soeiro, Maria Carolina Feres de Almeida; Leal, Tatiana de Carvalho Andreucci Torres; Serrano, Carlos Vicente; Oliveira Junior, Mucio Tavares de

2018-01-01

Despite having higher sensitivity as compared to conventional troponins, sensitive troponins have lower specificity, mainly in patients with renal failure. Study aimed at assessing the sensitive troponin I levels in patients with chest pain, and relating them to the existence of significant coronary lesions. Retrospective, single-center, observational. This study included 991 patients divided into two groups: with (N = 681) and without (N = 310) significant coronary lesion. For posterior analysis, the patients were divided into two other groups: with (N = 184) and without (N = 807) chronic renal failure. The commercial ADVIA Centaur® TnI-Ultra assay (Siemens Healthcare Diagnostics) was used. The ROC curve analysis was performed to identify the sensitivity and specificity of the best cutoff point of troponin as a discriminator of the probability of significant coronary lesion. The associations were considered significant when p renal failure, the areas under the ROC curve were 0.703 (95% CI: 0.66 - 0.74) and 0.608 (95% CI: 0.52 - 0.70), respectively. The best cutoff points to discriminate the presence of significant coronary lesion were: in the general population, 0.605 ng/dL (sensitivity, 63.4%; specificity, 67%); in patients without renal failure, 0.605 ng/dL (sensitivity, 62.7%; specificity, 71%); and in patients with chronic renal failure, 0.515 ng/dL (sensitivity, 80.6%; specificity, 42%). In patients with chest pain, sensitive troponin I showed a good correlation with significant coronary lesions when its level was greater than 0.605 ng/dL. In patients with chronic renal failure, a significant decrease in specificity was observed in the correlation of troponin levels and severe coronary lesions.

Factors independently associated with cardiac troponin I levels in young and healthy adults from the general population.

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Bossard, Matthias; Thériault, Sébastien; Aeschbacher, Stefanie; Schoen, Tobias; Kunz, Seraina; von Rotz, Mirco; Estis, Joel; Todd, John; Risch, Martin; Mueller, Christian; Risch, Lorenz; Paré, Guillaume; Conen, David

2017-02-01

Determinants of cardiomyocyte injury as quantified by high-sensitivity cardiac troponin I (cTnI) in young and healthy individuals, and sex-specific 99th percentiles are largely unknown. Our study included 2077 adults from the general population aged 25-41 years without cardiovascular disease. cTnI was measured using a high-sensitivity assay. We performed stepwise backward linear regression analyses to identify variables independently associated with hs-cTnI levels, and calculated narrow-sense heritability from 1638-genotyped participants. Median age was 37 years. cTnI was quantifiable in all but 11 participants (99.5 %). Median (interquartile range) cTnI was significantly higher in men than in women [0.99 (0.71; 1.65) versus 0.47 (0.33; 0.71) ng/L, p age, systolic blood pressure, heart rate, left ventricular mass, N-terminal pro B-type natriuretic peptide, and creatine kinase (all p age, and systolic blood pressure belong to the strongest determinants of hs-cTnI in healthy adults. The 99th percentile was three times higher in men compared to women. Hence, sex-specific cut-off values may be preferable when applying hs-cTnI for screening purposes. Our results may also improve the interpretation of cTn levels in daily clinical practice.

Is general anesthesia a risk for myocardium? Effect of anesthesia on myocardial function as assessed by cardiac troponin-i in two different groups (isofluran+N2O inhalation and propofol+fentanyl iv anesthesia

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Demet Dogan Erol

2007-11-01

Full Text Available Demet Dogan Erol1, Ibrahim Ozen21Department of Anaesthesiology and Reanimation, School of Medicine, Kocatepe University, Afyonkarahisar, Turkey; 2Department of Anaesthesiology and Reanimation, Karadeniz Technical University Faculty of Medicine, Trabzon, TurkeyBackground and objectives: Peroperative myocardial infarction (MI is the most common cause of morbidity and mortality. What is the role of general anesthesia in this process? Is general anesthesia a risk for myocardial infarction? The present study was designed to determine whether the measurement of serum levels of cardiac troponin I (cTnI, a highly sensitive and specific marker for cardiac injury, would help establish the diagnosis of myocardial infarction in two different types of anesthesia.Method: Elective abdominal hysterectomy was planned with the permission of the ethic committee in 40 patients who were 20–45 years range, in ASA-I group, and have a Goldman Cardiac Risk Index-0. The patients were divided into two groups. Isoflurane + N2O was administrated to first group, and Propofol + Fentanyl to second group. cTnI levels were determined before anesthesia, after induction before surgery and 9 hours after the second period respectively.Results: There was no significant difference between the groups by the means of demographic properties, hemodynamic parameters and cTnI levels, and the cTnI levels were determined under the basal levels in all samples.Conclusion: General anesthesia is not a risk for myocardial infarction to state eliminating risk factors and protection hemodynamia cardiac.Keywords: cardiac troponin-I, myocardial infarction, isofluran + N2O inhalation anesthesia, propofol + fentanyl intravenous anesthesia.

Cardiac troponin T and fast skeletal muscle denervation in ageing.

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Xu, Zherong; Feng, Xin; Dong, Juan; Wang, Zhong-Min; Lee, Jingyun; Furdui, Cristina; Files, Daniel Clark; Beavers, Kristen M; Kritchevsky, Stephen; Milligan, Carolanne; Jin, Jian-Ping; Delbono, Osvaldo; Zhang, Tan

2017-10-01

Ageing skeletal muscle undergoes chronic denervation, and the neuromuscular junction (NMJ), the key structure that connects motor neuron nerves with muscle cells, shows increased defects with ageing. Previous studies in various species have shown that with ageing, type II fast-twitch skeletal muscle fibres show more atrophy and NMJ deterioration than type I slow-twitch fibres. However, how this process is regulated is largely unknown. A better understanding of the mechanisms regulating skeletal muscle fibre-type specific denervation at the NMJ could be critical to identifying novel treatments for sarcopenia. Cardiac troponin T (cTnT), the heart muscle-specific isoform of TnT, is a key component of the mechanisms of muscle contraction. It is expressed in skeletal muscle during early development, after acute sciatic nerve denervation, in various neuromuscular diseases and possibly in ageing muscle. Yet the subcellular localization and function of cTnT in skeletal muscle is largely unknown. Studies were carried out on isolated skeletal muscles from mice, vervet monkeys, and humans. Immunoblotting, immunoprecipitation, and mass spectrometry were used to analyse protein expression, real-time reverse transcription polymerase chain reaction was used to measure gene expression, immunofluorescence staining was performed for subcellular distribution assay of proteins, and electromyographic recording was used to analyse neurotransmission at the NMJ. Levels of cTnT expression in skeletal muscle increased with ageing in mice. In addition, cTnT was highly enriched at the NMJ region-but mainly in the fast-twitch, not the slow-twitch, muscle of old mice. We further found that the protein kinase A (PKA) RIα subunit was largely removed from, while PKA RIIα and RIIβ are enriched at, the NMJ-again, preferentially in fast-twitch but not slow-twitch muscle in old mice. Knocking down cTnT in fast skeletal muscle of old mice: (i) increased PKA RIα and reduced PKA RIIα at the NMJ; (ii

Cardiac Magnetic Resonance Imaging in Myocarditis Reveals Persistent Disease Activity Despite Normalization of Cardiac Enzymes and Inflammatory Parameters at 3-Month Follow-Up.

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Berg, Jan; Kottwitz, Jan; Baltensperger, Nora; Kissel, Christine K; Lovrinovic, Marina; Mehra, Tarun; Scherff, Frank; Schmied, Christian; Templin, Christian; Lüscher, Thomas F; Heidecker, Bettina; Manka, Robert

2017-11-01

There is a major unmet need to identify high-risk patients in myocarditis. Although decreasing cardiac and inflammatory markers are commonly interpreted as resolving myocarditis, this assumption has not been confirmed as of today. We sought to evaluate whether routine laboratory parameters at diagnosis predict dynamic of late gadolinium enhancement (LGE) as persistent LGE has been shown to be a risk marker in myocarditis. Myocarditis was diagnosed based on clinical presentation, high-sensitivity troponin T, and cardiac magnetic resonance imaging, after exclusion of obstructive coronary artery disease by angiography. Cardiac magnetic resonance imaging was repeated at 3 months. LGE extent was analyzed with the software GT Volume. Change in LGE >20% was considered significant. Investigated cardiac and inflammatory markers included high-sensitivity troponin T, creatine kinase, myoglobin, N-terminal B-type natriuretic peptide, C-reactive protein, and leukocyte count. Twenty-four patients were enrolled. Absolute levels of cardiac enzymes and inflammatory markers at baseline did not predict change in LGE at 3 months. Cardiac and inflammatory markers had normalized in 21 patients (88%). LGE significantly improved in 16 patients (67%); however, it persisted to a lesser degree in 17 of them (71%) and increased in a small percentage (21%) despite normalization of cardiac enzymes. This is the first study reporting that cardiac enzymes and inflammatory parameters do not sufficiently reflect LGE in myocarditis. Although a majority of patients with normalizing laboratory markers experienced improved LGE, in a small percentage LGE worsened. These data suggest that cardiac magnetic resonance imaging might add value to currently existing diagnostic tools for risk assessment in myocarditis. © 2017 American Heart Association, Inc.

Economic evaluation of the one-hour rule-out and rule-in algorithm for acute myocardial infarction using the high-sensitivity cardiac troponin T assay in the emergency department.

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Apoorva Ambavane

Full Text Available The 1-hour (h algorithm triages patients presenting with suspected acute myocardial infarction (AMI to the emergency department (ED towards "rule-out," "rule-in," or "observation," depending on baseline and 1-h levels of high-sensitivity cardiac troponin (hs-cTn. The economic consequences of applying the accelerated 1-h algorithm are unknown.We performed a post-hoc economic analysis in a large, diagnostic, multicenter study of hs-cTnT using central adjudication of the final diagnosis by two independent cardiologists. Length of stay (LoS, resource utilization (RU, and predicted diagnostic accuracy of the 1-h algorithm compared to standard of care (SoC in the ED were estimated. The ED LoS, RU, and accuracy of the 1-h algorithm was compared to that achieved by the SoC at ED discharge. Expert opinion was sought to characterize clinical implementation of the 1-h algorithm, which required blood draws at ED presentation and 1h, after which "rule-in" patients were transferred for coronary angiography, "rule-out" patients underwent outpatient stress testing, and "observation" patients received SoC. Unit costs were for the United Kingdom, Switzerland, and Germany. The sensitivity and specificity for the 1-h algorithm were 87% and 96%, respectively, compared to 69% and 98% for SoC. The mean ED LoS for the 1-h algorithm was 4.3h-it was 6.5h for SoC, which is a reduction of 33%. The 1-h algorithm was associated with reductions in RU, driven largely by the shorter LoS in the ED for patients with a diagnosis other than AMI. The estimated total costs per patient were £2,480 for the 1-h algorithm compared to £4,561 for SoC, a reduction of up to 46%.The analysis shows that the use of 1-h algorithm is associated with reduction in overall AMI diagnostic costs, provided it is carefully implemented in clinical practice. These results need to be prospectively validated in the future.

Molecular Defects in Cardiac Myofilament Ca2+-Regulation Due to Cardiomyopathy-Linked Mutations Can Be Reversed by Small Molecules Binding to Troponin

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Alice Sheehan

2018-03-01

Full Text Available The inherited cardiomyopathies, hypertrophic cardiomyopathy (HCM and dilated cardiomyopathy (DCM are relatively common, potentially life-threatening and currently untreatable. Mutations are often in the contractile proteins of cardiac muscle and cause abnormal Ca2+ regulation via troponin. HCM is usually linked to higher myofilament Ca2+-sensitivity whilst in both HCM and DCM mutant tissue there is often an uncoupling of the relationship between troponin I (TnI phosphorylation by PKA and modulation of myofilament Ca2+-sensitivity, essential for normal responses to adrenaline. The adrenergic response is blunted, and this may predispose the heart to failure under stress. At present there are no compounds or interventions that can prevent or treat sarcomere cardiomyopathies. There is a need for novel therapies that act at a more fundamental level to affect the disease process. We demonstrated that epigallocatechin-3 gallate (EGCG was found to be capable of restoring the coupled relationship between Ca2+-sensitivity and TnI phosphorylation in mutant thin filaments to normal in vitro, independent of the mutation (15 mutations tested. We have labeled this property “re-coupling.” The action of EGCG in vitro to reverse the abnormality caused by myopathic mutations would appear to be an ideal pharmaceutical profile for treatment of inherited HCM and DCM but EGCG is known to be promiscuous in vivo and is thus unsuitable as a therapeutic drug. We therefore investigated whether other structurally related compounds can re-couple myofilaments without these off-target effects. We used the quantitative in vitro motility assay to screen 40 compounds, related to C-terminal Hsp90 inhibitors, and found 23 that can re-couple mutant myofilaments. There is no correlation between re-couplers and Hsp90 inhibitors. The Ca2+-sensitivity shift due to TnI phosphorylation was restored to 2.2 ± 0.01-fold (n = 19 compared to 2.0 ± 0.24-fold (n = 7 in wild-type thin

Molecular Defects in Cardiac Myofilament Ca2+-Regulation Due to Cardiomyopathy-Linked Mutations Can Be Reversed by Small Molecules Binding to Troponin.

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Sheehan, Alice; Messer, Andrew E; Papadaki, Maria; Choudhry, Afnan; Kren, Vladimír; Biedermann, David; Blagg, Brian; Khandelwal, Anuj; Marston, Steven B

2018-01-01

The inherited cardiomyopathies, hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are relatively common, potentially life-threatening and currently untreatable. Mutations are often in the contractile proteins of cardiac muscle and cause abnormal Ca 2+ regulation via troponin. HCM is usually linked to higher myofilament Ca 2+ -sensitivity whilst in both HCM and DCM mutant tissue there is often an uncoupling of the relationship between troponin I (TnI) phosphorylation by PKA and modulation of myofilament Ca 2+ -sensitivity, essential for normal responses to adrenaline. The adrenergic response is blunted, and this may predispose the heart to failure under stress. At present there are no compounds or interventions that can prevent or treat sarcomere cardiomyopathies. There is a need for novel therapies that act at a more fundamental level to affect the disease process. We demonstrated that epigallocatechin-3 gallate (EGCG) was found to be capable of restoring the coupled relationship between Ca 2+ -sensitivity and TnI phosphorylation in mutant thin filaments to normal in vitro , independent of the mutation (15 mutations tested). We have labeled this property "re-coupling." The action of EGCG in vitro to reverse the abnormality caused by myopathic mutations would appear to be an ideal pharmaceutical profile for treatment of inherited HCM and DCM but EGCG is known to be promiscuous in vivo and is thus unsuitable as a therapeutic drug. We therefore investigated whether other structurally related compounds can re-couple myofilaments without these off-target effects. We used the quantitative in vitro motility assay to screen 40 compounds, related to C-terminal Hsp90 inhibitors, and found 23 that can re-couple mutant myofilaments. There is no correlation between re-couplers and Hsp90 inhibitors. The Ca 2+ -sensitivity shift due to TnI phosphorylation was restored to 2.2 ± 0.01-fold ( n = 19) compared to 2.0 ± 0.24-fold ( n = 7) in wild-type thin filaments

Multi-centre evaluation of recent troponin assays for the diagnosis of NSTEMI

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Camille Chenevier-Gobeaux

2018-07-01

Full Text Available Objectives: We aimed to compare the use of nine different cardiac troponin (cTn assays (2 cTnT and 7 cTnI for the diagnosis of NSTEMI in a single multi-centre population. Design and methods: One hundred and fifty-eight patients were included (mean age 60 years, SD 17 years, including 23 patients (14% with NSTEMI. Results: The analytical comparison highlighted a large heterogeneity of cTn assays, as reflected by percentages of patients with detectable cTn, correlation coefficients, Passing-Bablok comparisons and concordance coefficients. Correlations within cTnI assays were good and correlation within cTnT assays was excellent. Diagnostic performances demonstrated that each cTn assay has specific threshold values. Furthermore, some assays (HS-cTnI and T, cTnI-Pathfast and cTnI-Centaur indicated high sensitivity and negative predictive value using the limit of detection (LoD diagnostic strategy. For the latter assays, a significant increase in specificity was found when using the 99th percentile or the H0-H3 strategies, in comparison to the LoD strategy. When applying the European Society of Cardiology H0-H3 algorithm, comparable diagnostic performances were obtained. Conclusion: All 9 cTn assays indicated overall good diagnostic performances for the diagnosis of NSTEMI in emergency departments when the recommended algorithm based on the variation of cTn value between two measurements at admission and 3 h later was used. Keywords: Cardiac troponin, High-sensitivity assay, Chest pain, Emergency department, NSTEMI, Analytical evaluation

Cardiac troponin I levels in canine pyometra

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Hagman Ragnvi

2007-02-01

Full Text Available Abstract Background Myocardial injury may contribute to unexpected deaths due to pyometra. To detect myocardial damage, measurement of cardiac troponin I (cTnI is currently the most sensitive and specific method. The aims of the present study were to evaluate presence of myocardial damage in canine pyometra by analysis of cTnI, to explore whether myocardial injury was associated with systemic inflammatory response syndrome (SIRS and to evaluate whether other clinical or laboratory parameters were associated with cTnI increase. Methods Preoperative plasma levels of cTnI were investigated in 58 female dogs with pyometra and 9 controls. The value of physical examination findings, haematological, serum biochemical and pro-inflammatory (CRP and TNF-α parameters as possible predictors of increased cTnI levels was also evaluated. Results Seven dogs with pyometra (12% and one control dog (11% had increased levels of cTnI. In the pyometra group, the levels ranged between 0.3–0.9 μg l-1 and in the control dog the level was 0.3 μg l-1. The cTnI levels did not differ significantly between the two groups. No cardiac abnormalities were evident on preoperative physical examinations. Four of the pyometra patients died within two weeks of surgery, of which two were examined post mortem. In one of these cases (later diagnosed with myocarditis and disseminated bacterial infection the cTnI levels increased from 0.9 μg l-1 preoperatively to 180 μg l-1 the following day when also heart arrhythmia was also detected. The other patient had cTnI levels of 0.7 μg l-1 with no detectable heart pathology post mortem. CTnI increase was not associated with presence of SIRS. There was a trend for the association of cTnI increase with increased mortality. No preoperative physical examination findings and few but unspecific laboratory parameters were associated with increased cTnI levels. Conclusion Increased cTnI levels were observed in 12% of the dogs with pyometra. The

Prognostic importance of troponin T and creatine kinase after elective angioplasty

NARCIS (Netherlands)

Nienhuis, Mark B.; Ottervanger, Jan Paul; Dikkeschei, Bert; Suryapranata, Harry; de Boer, Menko-Jan; Dambrink, Jan-Henk E.; Hoorntje, Jan C. A.; van't Hof, Arnoud W. J.; Gosselink, Marcel; Zijlstra, Felix

2007-01-01

Background: The prognostic importance of elevated cardiac enzymes after elective percutaneous coronary intervention has been debated. Therefore, we performed a prospective observational study to evaluate the prognostic value of postprocedural rise of troponin T and creatine kinase. Methods: Troponin

High-sensitivity troponin assays for the early rule-out or diagnosis of acute myocardial infarction in people with acute chest pain: A systematic review and cost-effectiveness analysis

NARCIS (Netherlands)

M. Westwood (Marie); T. van Asselt (Thea); B.L.T. Ramaekers (Bram); P. Whiting (Penny); P. Thokala (Praveen); M.A. Joore (Manuela); N. Armstrong (Nigel); J. Ross (Janine); J.L. Severens (Hans); J. Kleijnen (Jos)

2015-01-01

textabstractBackground The primary indication for this assessment is the early rule-out of acute myocardial infarction (AMI) in people presenting with acute chest pain and suspected, but not confirmed, non-ST segment elevation myocardial infarction (NSTEMI). Cardiac troponins (cTns) I and T are used

Chimeric recombinant antibody fragments in cardiac troponin I immunoassay.

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Hyytiä, Heidi; Heikkilä, Taina; Brockmann, Eeva-Christine; Kekki, Henna; Hedberg, Pirjo; Puolakanaho, Tarja; Lövgren, Timo; Pettersson, Kim

2015-03-01

To introduce a novel nanoparticle-based immunoassay for cardiac troponin I (cTnI) utilizing chimeric antibody fragments and to demonstrate that removal of antibody Fc-part and antibody chimerization decrease matrix related interferences. A sandwich-type immunoassay for cTnI based on recombinant chimeric (mouse variable/human constant) antigen binding (cFab) antibodies and intrinsically fluorescent nanoparticles was developed. To test whether using chimeric antibody fragments helps to avoid matrix related interferences, samples (n=39) with known amounts of triglycerides, bilirubin, rheumatoid factor (RF) or human anti-mouse antibodies (HAMAs) were measured with the novel assay, along with a previously published nanoparticle-based research assay with the same antibody epitopes. The limit of detection (LoD) was 3.30ng/L. Within-laboratory precision for 29ng/L and 2819ng/L cTnI were 13.7% and 15.9%, respectively. Regression analysis with Siemens ADVIA Centaur® yielded a slope (95% confidence intervals) of 0.18 (0.17-1.19) and a y-intercept of 1.94 (-1.28-3.91) ng/L. When compared to a previously published nanoparticle-based assay, the novel assay showed substantially reduced interference in the tested interference prone samples, 15.4 vs. 51.3%. A rheumatoid factor containing sample was decreased from 241ng/L to sensitive (LoD=3.3ng/L) immunoassay for the detection of cTnI and decreased matrix related interferences, thus resulting in a lower number of falsely elevated cTnI-values. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Rapid detection of cardiac troponin I using antibody-immobilized gate-pulsed AlGaN/GaN high electron mobility transistor structures

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Yang, Jiancheng; Carey, Patrick; Ren, Fan; Wang, Yu-Lin; Good, Michael L.; Jang, Soohwan; Mastro, Michael A.; Pearton, S. J.

2017-11-01

We report a comparison of two different approaches to detecting cardiac troponin I (cTnI) using antibody-functionalized AlGaN/GaN High Electron Mobility Transistors (HEMTs). If the solution containing the biomarker has high ionic strength, there can be difficulty in detection due to charge-screening effects. To overcome this, in the first approach, we used a recently developed method involving pulsed biases applied between a separate functionalized electrode and the gate of the HEMT. The resulting electrical double layer produces charge changes which are correlated with the concentration of the cTnI biomarker. The second approach fabricates the sensing area on a glass slide, and the pulsed gate signal is externally connected to the nitride HEMT. This produces a larger integrated change in charge and can be used over a broader range of concentrations without suffering from charge-screening effects. Both approaches can detect cTnI at levels down to 0.01 ng/ml. The glass slide approach is attractive for inexpensive cartridge-type sensors.

Origin of noise in liquid-gated Si nanowire troponin biosensors

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Kutovyi, Y.; Zadorozhnyi, I.; Hlukhova, H.; Handziuk, V.; Petrychuk, M.; Ivanchuk, Andriy; Vitusevich, S.

2018-04-01

Liquid-gated Si nanowire field-effect transistor (FET) biosensors are fabricated using a complementary metal-oxide-semiconductor-compatible top-down approach. The transport and noise properties of the devices reflect the high performance of the FET structures, which allows label-free detection of cardiac troponin I (cTnI) molecules. Moreover, after removing the troponin antigens the structures demonstrate the same characteristics as before cTnI detection, indicating the reusable operation of biosensors. Our results show that the additional noise is related to the troponin molecules and has characteristics which considerably differ from those usually recorded for conventional FETs without target molecules. We describe the origin of the noise and suggest that noise spectroscopy represents a powerful tool for understanding molecular dynamic processes in nanoscale FET-based biosensors.

Mechanism of troponin elevations in patients with acute ischemic stroke

DEFF Research Database (Denmark)

Jensen, Jesper K.; Atar, Dan; Mickley, Hans

2007-01-01

the introduction of troponin in the diagnosis of acute myocardial infarction, this marker has been measured in a number of other conditions as well. One of these conditions is acute ischemic stroke, causing diagnostic dilemmas for clinicians. Because various electrocardiographic alterations have also been reported...... in these patients, it has been suggested that elevated troponin levels are somehow neurologically mediated, thus not caused by direct cardiac release. In conclusion, this review examines the available studies that systematically measured troponin in patients with acute ischemic stroke to properly interpret troponin...... elevations in these patients Udgivelsesdato: 2007-Mar-15...

The Role of Biomarkers in Decreasing Risk of Cardiac Toxicity after Cancer Therapy

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Christine Henri

2016-01-01

Full Text Available With the improvement of cancer therapy, survival related to malignancy has improved, but the prevalence of long-term cardiotoxicity has also increased. Cancer therapies with known cardiac toxicity include anthracyclines, biologic agents (trastuzumab, and multikinase inhibitors (sunitinib. The most frequent presentation of cardiac toxicity is dilated cardiomyopathy associated with poorest prognosis. Monitoring of cardiac toxicity is commonly performed by assessment of left ventricular (LV ejection fraction, which requires a significant amount of myocardial damage to allow detection of cardiac toxicity. Accordingly, this creates the impetus to search for more sensitive and reproducible biomarkers of cardiac toxicity after cancer therapy. Different biomarkers have been proposed to that end, the most studied ones included troponin release resulting from cardiomyocyte damage and natriuretic peptides reflecting elevation in LV filling pressure and wall stress. Increase in the levels of troponin and natriuretic peptides have been correlated with cumulative dose of anthracycline and the degree of LV dysfunction. Troponin is recognized as a highly efficient predictor of early and chronic cardiac toxicity, but there remains some debate regarding the clinical usefulness of the measurement of natriuretic peptides because of divergent results. Preliminary data are available for other biomarkers targeting inflammation, endothelial dysfunction, myocardial ischemia, and neuregulin-1. The purpose of this article is to review the available data to determine the role of biomarkers in decreasing the risk of cardiac toxicity after cancer therapy.

Role of cardiac biomarkers (troponin I and CK-MB as predictors of quality of life and long-term outcome after cardiac surgery

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Bignami Elena

2009-01-01

Full Text Available Perioperative and postoperative morbidity and mortality associated with cardiac surgery affect both the outcome and quality of life. Markers such as troponin effectively predict short-term outcome. In a prospective cohort study in a University Hospital we assessed the role of cardiac biomarkers, also as predictors of long-term outcome and life quality after cardiac surgery with a three-year follow-up after conventional heart surgery. Patients were interviewed via phone calls with a structured questionnaire examining general health, functional status, activities of daily living, perception of life quality and need for hospital readmission. Descriptive statistics and multivariate analysis were performed. Out of 252 consecutive patients, 8 (3.2% died at the three years follow up: 7 for cardiac complications and 1 for cancer. Thirty-six patients (13.5% had hospital readmission for cardiac causes (mostly for atrial fibrillation or other arrhythmias (9.3%, but none needed cardiac surgical reintervention; 21 patients (7.9% were hospitalised for non-cardiac causes. No limitation in function activities of daily living was reported by most patients (94%, 92% perceived their general health as excellent, very good or good and none considered it insufficient; 80% were NYHA I, 17% NYHA II, 3% NYHA III and none NYHA IV. Multivariate analysis indicated preoperative treatment with digitalis or nitrates, and postoperative cardiac biomarkers release was independently associated to death. Elevated cardiac biomarker release and length of hospital stay were the only postoperative independent predictors of death in this study.

Troponin elevation in subarachnoid hemorrhage

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Ioannis N. Mavridis

2015-03-01

Full Text Available Troponin (tr elevation in aneurysmal subarachnoid hemorrhage (SAH patients is often difficult to be appropriately assessed by clinicians, causing even disagreements regarding its management between neurosurgeons and cardiologists. The purpose of this article was to review the literature regarding the clinical interpretation of tr elevation in SAH. We searched for articles in PubMed using the key words: “troponin elevation” and “subarachnoid hemorrhage”. All of them, as well as relative neurosurgical books, were used for this review. Some type of cardiovascular abnormality develops in most SAH patients. Neurogenic stunned myocardium is a frequent SAH complication, due to catecholamine surge which induces cardiac injury, as evidenced by increased serum tr levels, electrocardiographic (ECG changes and cardiac wall motion abnormalities. Tr elevation, usually modest, is an early and specific marker for cardiac involvement after SAH and its levels peak about two days after SAH. Cardiac tr elevation predictors include poor clinical grade, intraventricular hemorrhage, loss of consciousness at ictus, global cerebral edema, female sex, large body surface area, lower systolic blood pressure, higher heart rate and prolonged Q-Tc interval. Elevated tr levels are associated with disability and death (especially tr >1 μg/L, worse neurological grade, systolic and diastolic cardiac dysfunction, pulmonary congestion, longer intensive care unit stay and incidence of vasospasm. Tr elevation is a common finding in SAH patients and constitutes a rightful cause of worry about the patients' cardiac function and prognosis. It should be therefore early detected, carefully monitored and appropriately managed by clinicians.

A High-Performance Fluorescence Immunoassay Based on the Relaxation of Quenching, Exemplified by Detection of Cardiac Troponin I

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Seung-Wan Kim

2016-05-01

Full Text Available The intramolecular fluorescence self-quenching phenomenon is a major drawback in developing high-performance fluorometric biosensors which use common fluorophores as signal generators. We propose two strategies involving liberation of the fluorescent molecules by means of enzymatic fragmentation of protein or dehybridization of double-stranded DNA. In the former, bovine serum albumin (BSA was coupled with the fluorescent BODIPY dye (Red BSA, and then immobilized on a solid surface. When the insolubilized Red BSA was treated with proteinase K (10 units/mL for 30 min, the fluorescent signal was significantly increased (3.5-fold compared to the untreated control. In the second case, fluorophore-tagged DNA probes were linked to gold nanoparticles by hybridization with capture DNA strands densely immobilized on the surface. The quenched fluorescence signal was recovered (3.7-fold by thermal dehybridization, which was induced with light of a specific wavelength (e.g., 530 nm for less than 1 min. We next applied the Red BSA self-quenching relaxation technique employing enzymatic fragmentation to a high-performance immunoassay of cardiac troponin I (cTnI in a microtiter plate format. The detection limit was 0.19 ng/mL cTnI, and the fluorescent signal was enhanced approximately 4.1-fold compared with the conventional method of direct measurement of the fluorescent signal from a non-fragmented fluorophore-labeled antibody.

Prevalence and significance of troponin elevations in patients without acute coronary disease

DEFF Research Database (Denmark)

Vestergaard, Kirstine Roll; Jespersen, Camilla Bang; Arnadottir, Asthildur

2016-01-01

BACKGROUND: Cardiac troponin T and I are important diagnostic and prognostic markers in patients with acute coronary syndrome (ACS). Troponin elevations in various non-ACS scenarios have been documented, but few studies have been conducted on the general hospitalized population, none compared...

Effects of the whole-body cryotherapy on NTproBNP, hsCRP and troponin I in athletes.

Science.gov (United States)

Banfi, Giuseppe; Melegati, Gianluca; Barassi, Alessandra; d'Eril, Gianlodovico Melzi

2009-11-01

Whole-body cryotherapy refers to brief exposure to very cold air for treating symptoms of various illnesses. In sports medicine, whole-body cryotherapy is administered to improve recovery from muscular trauma. As specific studies are lacking, we measured cardiac markers in 10 top-level rugby players of the Italian National team before and after a 1-week course of daily sessions of whole-body cryotherapy. All subjects continued with the same training workload as that of the previous weeks. N-terminal pro B-type natriuretic peptide (NTproBNP) levels increased but remained within the normal range, whilst troponin I (TnI) and high sensitivity C-reactive protein (hsCRP) were unchanged. Whole-body cryotherapy did not impair cardiac function in this sample of elite athletes.

Clinical performance of a new point-of-care cardiac troponin I test.

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Christ, Michael; Geier, Felicitas; Blaschke, Sabine; Giannitsis, Evangelos; Khellaf, Mehdi; Mair, Johannes; Pariente, David; Scharnhorst, Volkher; Semjonow, Veronique; Hausfater, Pierre

2018-04-09

We evaluated the clinical performance of the Minicare cardiac troponin-I (cTnI), a new point-of-care (POC) cTnI test for the diagnosis of acute myocardial infarction (AMI) in a prospective, multicentre study (ISRCTN77371338). Of 474 patients (≥18 years) admitted to an emergency department (ED) or chest pain unit (CPU) with symptoms suggestive of acute coronary syndrome (ACS; ≤12 h from symptom onset), 465 were eligible. Minicare cTnI was tested immediately, 3 h and 6 h after presentation. AMI diagnoses were adjudicated independently based on current guidelines. The diagnostic performance of the Minicare cTnI test at 3 h was similar for whole blood and in plasma: sensitivity 0.92 vs. 0.90; specificity 0.91 vs. 0.90; positive predictive value (PPV) 0.68 vs. 0.66; negative predictive value (NPV) 0.98 vs. 0.98; positive likelihood ratio (LR+) 10.18 vs. 9.41; negative likelihood ratio (LR-) 0.09 vs. 0.11. The optimal diagnostic performance was obtained at 3 h using cut-offs cTnI >43 ng/L plus cTnI change from admission ≥18.5 ng/L: sensitivity 0.90, specificity 0.96, PPV 0.81, NPV 0.98, and LR+ 21.54. The area under the receiver operating characteristics (ROC) curve for cTnI whole blood baseline value and absolute change after 3 h curve was 0.93. These data support the clinical usefulness of Minicare cTnI within a 0 h/3 h-blood sampling protocol supported by current guidelines for the evaluation of suspected ACS.

High-Sensitivity Troponin: A Clinical Blood Biomarker for Staging Cardiomyopathy in Fabry Disease.

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Seydelmann, Nora; Liu, Dan; Krämer, Johannes; Drechsler, Christiane; Hu, Kai; Nordbeck, Peter; Schneider, Andreas; Störk, Stefan; Bijnens, Bart; Ertl, Georg; Wanner, Christoph; Weidemann, Frank

2016-05-31

High-sensitivity troponin (hs-TNT), a biomarker of myocardial damage, might be useful for assessing fibrosis in Fabry cardiomyopathy. We performed a prospective analysis of hs-TNT as a biomarker for myocardial changes in Fabry patients and a retrospective longitudinal follow-up study to assess longitudinal hs-TNT changes relative to fibrosis and cardiomyopathy progression. For the prospective analysis, hs-TNT from 75 consecutive patients with genetically confirmed Fabry disease was analyzed relative to typical Fabry-associated echocardiographic findings and total myocardial fibrosis as measured by late gadolinium enhancement (LE) on magnetic resonance imaging. Longitudinal data (3.9±2.0 years), including hs-TNT, LE, and echocardiographic findings from 58 Fabry patients, were retrospectively collected. Hs-TNT level positively correlated with LE (linear correlation coefficient, 0.72; odds ratio, 32.81 [95% CI, 3.56-302.59]; P=0.002); patients with elevated baseline hs-TNT (>14 ng/L) showed significantly increased LE (median: baseline, 1.9 [1.1-3.3] %; follow-up, 3.2 [2.3-4.9] %; PFabry disease and a qualified predictor of cardiomyopathy progression. Thus, hs-TNT could be helpful for staging and follow-up of Fabry patients. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Elevated Troponin Serum Levels in Adult Onset Still’s Disease

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Carlo Umberto Manzini

2015-01-01

Full Text Available Adult onset Still’s disease (AOSD is a rare inflammatory systemic disease that occasionally may affect myocardium. Diagnosis is based on typical AOSD symptoms after the exclusion of well-known infectious, neoplastic, or autoimmune/autoinflammatory disorders. In the case of abrupt, recent onset AOSD, it could be particularly difficult to make the differential diagnosis and in particular to early detect the possible heart involvement. This latter event is suggested by the clinical history of the four patients described here, incidentally observed at our emergency room. All cases were referred because of acute illness (high fever, malaise, polyarthralgias, skin rash, and sore throat, successively classified as AOSD, and they presented abnormally high levels of serum troponin without overt symptoms of cardiac involvement. The timely treatment with steroids (3 cases or ibuprofen (1 case leads to the remission of clinicoserological manifestations within few weeks. These observations suggest that early myocardial injury might be underestimated or entirely overlooked in patients with AOSD; routine cardiac assessment including troponin evaluation should be mandatory in all patients with suspected AOSD.

Blood troponin levels in acute cardiac events depends on space weather activity components (a correlative study).

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Stoupel, Eliiyahu; Radishauskas, Richardas; Bernotiene, Gailute; Tamoshiunas, Abdonas; Virvichiute, Daiva

2018-02-05

Many biological processes are influenced by space weather activity components such as solar activity (SA), geomagnetic activity (GMA) and cosmic ray activity (CRA). Examples are total mortality, acute myocardial infarction (AMI), stroke (cerebrovascular accident), sudden cardiac death, some congenital maladies (congenital heart disease and Down syndrome), many events in neonatology, ophtalmology, blood pressure regulation, blood coagulation, inflammation, etc. The aim of this study was to check if the level of blood troponins (Tns) - markers of myocardial damage and recognized components of modern description of AMI - is connected with the mentioned space weather parameters. Patients admitted to a 3000-bed tertiary university hospital in Kaunas, Lithuania, with suspected AMI were the object of the study. Data for the time between 2008 and 2013 - 72 consecutive months - were studied. Of the patients, 1896 (1398 male, 498 female) had elevated troponin I (Tn I) or troponin T (Tn T, sensitive Tn) levels. Normal values were 0.00-0.03 ng/mL for Tn I and 0.00-14.00 ng/mL for Tn T. Monthly means and standard deviation of Tn I and Tn T were compared with monthly markers of SA, GMA and CRA. Pearson correlation coefficients and their probabilities were established (in addition to the consecutive graphs of both comparing physical and biological data). The cosmophysical data came from space service institutions in the United States, Russia and Finland. AMI was diagnosed in 1188 patients (62.66%), and intermediate coronary syndrome in 698 patients (36.81%). There were significant links of the Tn blood levels with four SA indices and CRA (neutron activity in imp/min); there was no significant correlation with GMA indices Ap and Cp (p=0.27 and p=0.235). Tn T levels significantly correlated with the GMA indices and not with the SA and CRA levels (Ap: r=0.77, p=0.0021; Cp: r=0.729, p=0.0047). First, the monthly level of blood Tn I in ACS is significantly correlated with the indices

Quantitative troponin and death, cardiogenic shock, cardiac arrest and new heart failure in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS): insights from the Global Registry of Acute Coronary Events.

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Jolly, Sanjit S; Shenkman, Heather; Brieger, David; Fox, Keith A; Yan, Andrew T; Eagle, Kim A; Steg, P Gabriel; Lim, Ki-Dong; Quill, Ann; Goodman, Shaun G

2011-02-01

The objective of this study was to determine if the extent of quantitative troponin elevation predicted mortality as well as in-hospital complications of cardiac arrest, new heart failure and cardiogenic shock. 16,318 patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS) from the Global Registry of Acute Coronary Events (GRACE) were included. The maximum 24 h troponin value as a multiple of the local laboratory upper limit of normal was used. The population was divided into five groups based on the degree of troponin elevation, and outcomes were compared. An adjusted analysis was performed using quantitative troponin as a continuous variable with adjustment for known prognostic variables. For each approximate 10-fold increase in the troponin ratio, there was an associated increase in cardiac arrest, sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) (1.0, 2.4, 3.4, 5.9 and 13.4%; p<0.001 for linear trend), cardiogenic shock (0.5, 1.4, 2.0, 4.4 and 12.7%; p<0.001), new heart failure (2.5, 5.1, 7.4, 11.6 and 15.8%; p<0.001) and mortality (0.8, 2.2, 3.0, 5.3 and 14.0%; p<0.001). These findings were replicated using the troponin ratio as a continuous variable and adjusting for covariates (cardiac arrest, sustained VT or VF, OR 1.56, 95% CI 1.39 to 1.74; cardiogenic shock, OR 1.87, 95% CI 1.61 to 2.18; and new heart failure, OR 1.57, 95% CI 1.45 to 1.71). The degree of troponin elevation was predictive of early mortality (HR 1.61, 95% CI 1.44 to 1.81; p<0.001 for days 0-14) and longer term mortality (HR 1.18, 95% CI 1.07 to 1.30, p=0.001 for days 15-180). The extent of troponin elevation is an independent predictor of morbidity and mortality.

Molecular Defects in Cardiac Myofilament Ca2+-Regulation Due to Cardiomyopathy-Linked Mutations Can Be Reversed by Small Molecules Binding to Troponin

Czech Academy of Sciences Publication Activity Database

Sheehan, A.; Messer, A.E.; Papadaki, M.; Choudhry, A.; Křen, Vladimír; Biedermann, David; Blagg, B.; Khandelwal, A.; Marston, S.B.

2018-01-01

Roč. 9, MAR 27 2018 (2018), č. článku 243. ISSN 1664-042X R&D Projects: GA MZd(CZ) NV16-27317A Institutional support: RVO:61388971 Keywords : cardiomyopathy * sarcomeric protein mutations * troponin I phosphorylation OBOR OECD: Cardiac and Cardiovascular systems Impact factor: 4.134, year: 2016

Coronary atherosclerosis and adverse outcomes in patients with recent-onset atrial fibrillation and troponin rise.

Science.gov (United States)

Conti, Alberto; Angeli, Elena; Scorpiniti, Margherita; Alesi, Andrea; Trausi, Federica; Lazzeretti, Delia; Padeletti, Luigi; Gensini, Gian Franco

2015-10-01

The relationship between troponin and atrial fibrillation (AF) without acute coronary syndrome is still unclear. We sought to investigate the presence of coronary atherosclerosis and adverse outcomes in patients with AF. Consecutive patients with recent-onset AF and without severe comorbidities were enrolled between 2004 and 2013. Patients with a troponin rise or with adverse outcomes were considered for coronary angiography and revascularization when "critical" stenosis (≥70%) was recognized. Propensity score matching was performed to adjust for baseline characteristics; after matching, no differences existed between the groups of patients with or without troponin rise. The primary end point was the composite of acute coronary syndrome, revascularization, and cardiac death at 1- and 12-month follow-ups. Of 3627 patients enrolled, 3541 completed the study; 202 (6%) showed troponin rise; and 91 (3%), an adverse outcome. In the entire cohort, on multivariate analysis, the odds ratio for the occurrence of the primary end point of troponin rise was 14 (95% confidence interval [CI], 10-23; Prise was 10 (CI, 4-22; Prise achieved the primary end point in 38 (19%) and 43 (1%) patients, respectively (Prise showed higher prevalence of coronary atherosclerosis and adverse cardiac events. Stroke per se did not succeed in justifying the high morbidity. Thus, beyond stroke, coronary atherosclerosis might have a pivotal role in poor outcomes. Copyright © 2015 Elsevier Inc. All rights reserved.

Association of Elevated High Sensitivity Cardiac Troponin T(hs-cTnT Levels with Hemorrhagic Transformation and 3-Month Mortality in Acute Ischemic Stroke Patients with Rheumatic Heart Disease in China.

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Junfeng Liu

Full Text Available Elevated levels of high sensitivity cardiac troponin T (hs-cTnT occur in a substantial proportion of patients with acute ischemic stroke (AIS and can predict poor outcome and mortality after stroke. Whether elevated hs-cTnT levels can also predict hemorrhagic transformation (HT or prognosis in AIS patients with rheumatic heart disease (RHD remains unclear.Data from the Chengdu Stroke Registry on consecutive AIS patients with RHD admitted to West China Hospital within 1 month of stroke onset from October 2011 to February 2014 were examined. Clinico-demographic characteristics, HT, functional outcomes and stroke recurrence were compared between patients with elevated hs-cTnT levels (≥14 ng/L and patients with normal hs-cTnT levels (<14 ng/L.The final analysis involved 84 patients (31 males; mean age, 61.6±12.2 years, of whom serum hs-cTnT levels were elevated in 58.3%. Renal impairment was independently associated with elevated hs-cTnT levels (OR 4.184, 95%CI 1.17 to 15.01, P = 0.028, and patients with elevated hs-cTnT levels were at significantly higher risk of HT, 3-month mortality and 3-month disability/mortality (all P≤0.029. After controlling for age, sex, hypertension, renal impairment and National Institutes of Health Stroke Scale score on admission, the risk of HT and 3-month mortality was, respectively, 4.0- and 5.5-fold higher in patients with elevated hs-cTnT levels than in patients with normal hs-cTnT levels.Elevated hs-cTnT levels are independently associated with HT and 3-month mortality in AIS patients with RHD. These results with a small cohort should be verified and extended in large studies.

Troponin C Mutations Partially Stabilize the Active State of Regulated Actin and Fully Stabilize the Active State When Paired with Δ14 TnT.

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Baxley, Tamatha; Johnson, Dylan; Pinto, Jose R; Chalovich, Joseph M

2017-06-13

Striated muscle contraction is regulated by the actin-associated proteins tropomyosin and troponin. The extent of activation of myosin ATPase activity is lowest in the absence of both Ca 2+ and activating cross-bridges (i.e., S1-ADP or rigor S1). Binding of activating species of myosin to actin at a saturating Ca 2+ concentration stabilizes the most active state (M state) of the actin-tropomyosin-troponin complex (regulated actin). Ca 2+ binding alone produces partial stabilization of the active state. The extent of stabilization at a saturating Ca 2+ concentration depends on the isoform of the troponin subunits, the phosphorylation state of troponin, and, in the case of cardiac muscle, the presence of hypertrophic cardiomyopathy-producing mutants of troponin T and troponin I. Cardiac dysfunction is also associated with mutations of troponin C (TnC). Troponin C mutants A8V, C84Y, and D145E increase the Ca 2+ sensitivity of ATPase activity. We show that these mutants change the distribution of regulated actin states. The A8V and C84Y TnC mutants decreased the inactive B state distribution slightly at low Ca 2+ concentrations, but the D145E mutants had no effect on that state. All TnC mutants increased the level of the active M state compared to that of the wild type, at a saturating Ca 2+ concentration. Troponin complexes that contained two mutations that stabilize the active M state, A8V TnC and Δ14 TnT, appeared to be completely in the active state in the presence of only Ca 2+ . Because Ca 2+ gives full activation, in this situation, troponin must be capable of positioning tropomyosin in the active M state without the need for rigor myosin binding.

The diagnostic value of troponin in critically ill.

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Voga, Gorazd

2010-01-01

Troponin T and I are sensitive and specific markers of myocardial necrosis. They are used for the routine diagnosis of acute coronary syndrome. In critically ill patients they are basic diagnostic tool for diagnosis of myocardial necrosis due to myocardial ischemia. Moreover, the increase of troponin I and T is related with adverse outcome in many subgroups of critically ill patients. The new, high sensitivity tests which have been developed recently allow earlier and more accurate diagnosis of acute coronary syndrome. The use of the new tests has not been studied in critically ill patients, but they will probably replace the old tests and will be used on the routine basis.

5A.01: CORONARY ATHEROSCLEROSIS AND ADVERSE OUTCOME IN HYPERTENSIVE PATIENTS WITH RECENT-ONSET ATRIAL FIBRILLATION AND TROPONIN RISE.

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Conti, A; Angeli, E; Trausi, F; Grifoni, C; Lazzeretti, D; Bianchi, S; Catarzi, S; Covelli, A; Perrotta, M E; Lencioni, A M; Pisani, N; Bertolini, L

2015-06-01

Atrial fibrillation (AF), the most common cardiac-arrhythmia in critical-care, has reached a high prevalence in hypertensive patients. Prevention of systemic-embolism is mandatory; unfortunately, evidence to support the treatment of comorbidities as coronary artery disease (CAD) that contribute to excess mortality is lacking, and the mechanism underlying the troponin-rise during AF without acute coronary syndrome (ACS) is unclear. This study investigates the relationship between CAD, stroke and outcomes in patients with troponin-rise and AF. Patients with a recent-onset AF and without severe comorbidities were enrolled. Baseline characteristics in those with troponin-rise versus those without were adjusted with propensity-score-matching for possible confounders. SPSS-software allowed estimation of the propensity-score using logistic-regression and specifying nearest-neighbor matching in prior-stroke, heart-rate, hypertension, TIMI-risk-score, GRACE-score, CHA2DS2Vasc-score. Patients with a troponin-rise or cardiovascular event (CVE) were considered for angiography. The primary endpoint was the composite of ACS, revascularization (with critical CAD>/ = 70%) and cardiac-death at the follow-up; the secondary endpoint was stroke. Out of 6203 AF patients without severe comorbidities, 3541 with recent-onset AF completed the study; 202(6%) showed a troponin-rise, 91(3%) a CVE. After matching no difference existed in baseline characteristics. On multivariate analysis, in the entire cohort, troponin-rise, know-CAD and hypertension were predictors of the endpoint, whereas only troponin-rise (Odd Ratio, OR: 10, Confidence Interval 95%, CI: 4-22, p  2 (OR 4, CI 2-9, p rise achieved the endpoint in 38(19%) and 43(1%), respectively (p  0.50 ng/L with 55% and 75%, respectively. Patients with a recent-onset AF and troponin-rise showed a high prevalence of CVE but not stroke, thus CAD might have a role in poor outcomes.

Commutability of possible external quality assessment materials for cardiac troponin measurement.

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Shunli Zhang

Full Text Available The measurement of cardiac troponin is crucial in the diagnosis of myocardial infarction. The performance of troponin measurement is most conveniently monitored by external quality assessment (EQA programs. The commutability of EQA samples is often unknown and the effectiveness of EQA programs is limited.Commutability of possible EQA materials was evaluated. Commercial control materials used in an EQA program, human serum pools prepared from patient samples, purified analyte preparations, swine sera from model animals and a set of patient samples were measured for cTnI with 4 assays including Abbott Architect, Beckman Access, Ortho Vitros and Siemens Centaur. The measurement results were logarithm-transformed, and the transformed data for patient samples were pairwise analyzed with Deming regression and 95% prediction intervals were calculated for each pair of assays. The commutability of the materials was evaluated by comparing the logarithmic results of the materials with the limits of the intervals. Matrix-related biases were estimated for noncommutable materials. The impact of matrix-related bias on EQA was analyzed and a possible correction for the bias was proposed.Human serum pools were commutable for all assays; purified analyte preparations were commutable for 2 of the 6 assay pairs; commercial control materials and swine sera were all noncommutable; swine sera showed no reactivity to Vitros assay. The matrix-related biases for noncommutable materials ranged from -83% to 944%. Matrix-related biases of the EQA materials caused major abnormal between-assay variations in the EQA program and correction of the biases normalized the variations.Commutability of materials has major impact on the effectiveness of EQA programs for cTnI measurement. Human serum pools prepared from patient samples are commutable and other materials are mostly noncommutable. EQA programs should include at least one human serum pool to allow proper interpretation of

Diabetes Mellitus, Microalbuminuria, and Subclinical Cardiac Disease: Identification and Monitoring of Individuals at Risk of Heart Failure.

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Swoboda, Peter P; McDiarmid, Adam K; Erhayiem, Bara; Ripley, David P; Dobson, Laura E; Garg, Pankaj; Musa, Tarique A; Witte, Klaus K; Kearney, Mark T; Barth, Julian H; Ajjan, Ramzi; Greenwood, John P; Plein, Sven

2017-07-17

Patients with type 2 diabetes mellitus and elevated urinary albumin:creatinine ratio (ACR) have increased risk of heart failure. We hypothesized this was because of cardiac tissue changes rather than silent coronary artery disease. In a case-controlled observational study 130 subjects including 50 ACR+ve diabetes mellitus patients with persistent microalbuminuria (ACR >2.5 mg/mol in males and >3.5 mg/mol in females, ≥2 measurements, no previous renin-angiotensin-aldosterone therapy, 50 ACR-ve diabetes mellitus patients and 30 controls underwent cardiovascular magnetic resonance for investigation of myocardial fibrosis, ischemia and infarction, and echocardiography. Thirty ACR+ve patients underwent further testing after 1-year treatment with renin-angiotensin-aldosterone blockade. Cardiac extracellular volume fraction, a measure of diffuse fibrosis, was higher in diabetes mellitus patients than controls (26.1±3.4% and 23.3±3.0% P =0.0002) and in ACR+ve than ACR-ve diabetes mellitus patients (27.2±4.1% versus 25.1±2.9%, P =0.004). ACR+ve patients also had lower E' measured by echocardiography (8.2±1.9 cm/s versus 8.9±1.9 cm/s, P =0.04) and elevated high-sensitivity cardiac troponin T 18% versus 4% ≥14 ng/L ( P =0.05). Rate of silent myocardial ischemia or infarction were not influenced by ACR status. Renin-angiotensin-aldosterone blockade was associated with increased left ventricular ejection fraction (59.3±7.8 to 61.5±8.7%, P =0.03) and decreased extracellular volume fraction (26.5±3.6 to 25.2±3.1, P =0.01) but no changes in diastolic function or high-sensitivity cardiac troponin T levels. Asymptomatic diabetes mellitus patients with persistent microalbuminuria have markers of diffuse cardiac fibrosis including elevated extracellular volume fraction, high-sensitivity cardiac troponin T, and diastolic dysfunction, which may in part be reversible by renin-angiotensin-aldosterone blockade. Increased risk in these patients may be mediated by

Cardiac Stress and Inflammatory Markers as Predictors of Heart Failure in Patients With Type 2 Diabetes : The ADVANCE Trial

NARCIS (Netherlands)

Ohkuma, Toshiaki; Jun, Min; Woodward, Mark; Zoungas, Sophia; Cooper, Mark E; Grobbee, Diederick E; Hamet, Pavel; Mancia, Giuseppe; Williams, Bryan; Welsh, Paul; Sattar, Naveed; Shaw, Jonathan E.; Rahimi, Kazem; Chalmers, John

OBJECTIVE: This study examined the individual and combined effect of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), interleukin-6 (IL-6), and hs-CRP on the prediction of heart failure incidence or progression in patients with type 2 diabetes.

Serial High-Sensitivity Troponin T in Post-Primary Angioplasty Exercise Test

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Humberto Andres Vaz

2016-04-01

Full Text Available Abstract Background: The kinetics of high-sensitivity troponin T (hscTnT release should be studied in different situations, including functional tests with transient ischemic abnormalities. Objective: To evaluate the release of hscTnT by serial measurements after exercise testing (ET, and to correlate hscTnT elevations with abnormalities suggestive of ischemia. Methods: Patients with acute ST-segment elevation myocardial infarction (STEMI undergoing primary angioplasty were referred for ET 3 months after infarction. Blood samples were collected to measure basal hscTnT immediately before (TnT0h, 2 (TnT2h, 5 (TnT5h, and 8 hours (TnT8h after ET. The outcomes were peak hscTnT, TnT5h/TnT0h ratio, and the area under the blood concentration-time curve (AUC for hscTnT levels. Log-transformation was performed on hscTnT values, and comparisons were assessed with the geometric mean ratio, along with their 95% confidence intervals. Statistical significance was assessed by analysis of covariance with no adjustment, and then, adjusted for TnT0h, age and sex, followed by additional variables (metabolic equivalents, maximum heart rate achieved, anterior wall STEMI, and creatinine clearance. Results: This study included 95 patients. The highest geometric means were observed at 5 hours (TnT5h. After adjustments, peak hscTnT, TnT5h/TnT0h and AUC were 59% (p = 0.002, 59% (p = 0.003 and 45% (p = 0.003 higher, respectively, in patients with an abnormal ET as compared to those with normal tests. Conclusion: Higher elevations of hscTnT may occur after an abnormal ET as compared to a normal ET in patients with STEMI.

Serial High-Sensitivity Troponin T in Post-Primary Angioplasty Exercise Test

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Vaz, Humberto Andres, E-mail: humbertovaz@cardiol.br; Vanz, Ana Paula; Castro, Iran [Instituto de Cardiologia - Fundação Universitária de Cardiologia, Porto Alegre, RS (Brazil)

2016-04-15

The kinetics of high-sensitivity troponin T (hscTnT) release should be studied in different situations, including functional tests with transient ischemic abnormalities. To evaluate the release of hscTnT by serial measurements after exercise testing (ET), and to correlate hscTnT elevations with abnormalities suggestive of ischemia. Patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary angioplasty were referred for ET 3 months after infarction. Blood samples were collected to measure basal hscTnT immediately before (TnT{sub 0h}), 2 (TnT{sub 2h}), 5 (TnT{sub 5h}), and 8 hours (TnT{sub 8h}) after ET. The outcomes were peak hscTnT, TnT{sub 5h}/TnT{sub 0h} ratio, and the area under the blood concentration-time curve (AUC) for hscTnT levels. Log-transformation was performed on hscTnT values, and comparisons were assessed with the geometric mean ratio, along with their 95% confidence intervals. Statistical significance was assessed by analysis of covariance with no adjustment, and then, adjusted for TnT{sub 0h}, age and sex, followed by additional variables (metabolic equivalents, maximum heart rate achieved, anterior wall STEMI, and creatinine clearance). This study included 95 patients. The highest geometric means were observed at 5 hours (TnT{sub 5h}). After adjustments, peak hscTnT, TnT{sub 5h}/TnT{sub 0h} and AUC were 59% (p = 0.002), 59% (p = 0.003) and 45% (p = 0.003) higher, respectively, in patients with an abnormal ET as compared to those with normal tests. Higher elevations of hscTnT may occur after an abnormal ET as compared to a normal ET in patients with STEMI.

Nanocomposites of gold nanoparticles and graphene oxide towards an stable label-free electrochemical immunosensor for detection of cardiac marker troponin-I.

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Liu, Guozhen; Qi, Meng; Zhang, Yin; Cao, Chaomin; Goldys, Ewa M

2016-02-25

A stable label-free amperometric immunosensor is presented based on gold nanoparticles and graphene oxide nanocomposites for detection of cardiac troponin-I in the early diagnosis of myocardial infarction. For designing of the sensing platform, firstly the nanocomposites based on GO and AuNPs were prepared and anchored on electrode surfaces. The formed nanocomposites provided a platform with big surface area for loading anti-cTnI capture antibody, and worked as a bridge for fast electron transfer subsequently increased the sensitivity. Moreover, the linkages between AuNP, GO, and electrodes were based on covalent bonding by aryldiazonium salt coupling chemistry, which favors the stability of the sensing interface. Finally, the anti-cTnI detection antibody was immobilized on GO tailored with ferrocene molecules, functioning as the signal reporter for the detection of cTnI. The modification process was monitored using electrochemistry, SEM, XPS. The herein immunosensor demonstrates a good selectivity and high sensitivity against human-cTnI, and is capable of detecting cTnI at concentrations as low as 0.05 ng mL(-1), which is 100 times lower than that possible by conventional methods. It is potential to design the portable sensing platform based on AuNPs and GO nanocomposites for future point-of-care diagnostics. Copyright © 2015 Elsevier B.V. All rights reserved.

Functional effects of the DCM mutant Gly159Asp troponin C in skinned muscle fibres

DEFF Research Database (Denmark)

Preston, Laura C; Lipscomb, Simon; Robinson, Paul

2006-01-01

We recently reported a dilated cardiomyopathy (DCM) causing mutation in a novel disease gene, TNNC1, which encodes cardiac troponin C (TnC). We have determined how this mutation, Gly159Asp, affects contractile regulation when incorporated into muscle fibres. Endogenous troponin in rabbit skinned...

Association between Angiotensin-Converting Enzyme Inhibitors and Troponin in Acute Coronary Syndrome

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Luiz Minuzzo

2014-12-01

Full Text Available Background: Cardiovascular disease is the leading cause of mortality in the western world and its treatment should be optimized to decrease severe adverse events. Objective: To determine the effect of previous use of angiotensin-converting enzyme inhibitors on cardiac troponin I measurement in patients with acute coronary syndrome without ST-segment elevation and evaluate clinical outcomes at 180 days. Methods: Prospective, observational study, carried out in a tertiary center, in patients with acute coronary syndrome without ST-segment elevation. Clinical, electrocardiographic and laboratory variables were analyzed, with emphasis on previous use of angiotensin-converting enzyme inhibitors and cardiac troponin I. The Pearson chi-square tests (Pereira or Fisher's exact test (Armitage were used, as well as the non-parametric Mann-Whitney's test. Variables with significance levels of 0.5 ng / mL were high blood glucose at admission (p = 0.0034 and ST-segment depression ≥ 0.5 mm in one or more leads (p = 0.0016. The use of angiotensin-converting inhibitors prior to hospitalization was associated with troponin ≤ 0.5 ng / mL (p = 0.0482. The C-statistics for this model was 0.77. Conclusion: This study showed a correlation between prior use of angiotensin-converting enzyme inhibitors and reduction in the myocardial necrosis marker troponin I in patients admitted for acute coronary syndrome without ST-segment elevation. However, there are no data available yet to state that this reduction could lead to fewer severe clinical events such as death and re-infarction at 180 days.

Age-adjusted high-sensitivity troponin T cut-off value for risk stratification of pulmonary embolism.

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Kaeberich, Anja; Seeber, Valerie; Jiménez, David; Kostrubiec, Maciej; Dellas, Claudia; Hasenfuß, Gerd; Giannitsis, Evangelos; Pruszczyk, Piotr; Konstantinides, Stavros; Lankeit, Mareike

2015-05-01

High-sensitivity troponin T (hsTnT) helps in identifying pulmonary embolism patients at low risk of an adverse outcome. In 682 normotensive pulmonary embolism patients we investigate whether an optimised hsTnT cut-off value and adjustment for age improve the identification of patients at elevated risk. Overall, 25 (3.7%) patients had an adverse 30-day outcome. The established hsTnT cut-off value of 14 pg·mL(-1) retained its high prognostic value (OR (95% CI) 16.64 (2.24-123.74); p=0.006) compared with the cut-off value of 33 pg·mL(-1) calculated by receiver operating characteristic analysis (7.14 (2.64-19.26); pvalue of 45 pg·mL(-1) but not the established cut-off value of 14 pg·mL(-1) predicted an adverse outcome. An age-adjusted hsTnT cut-off value (≥14 pg·mL(-1) for patients aged risk (12.4% adverse outcome). Risk assessment of normotensive pulmonary embolism patients was improved by the introduction of an age-adjusted hsTnT cut-off value. A three-step approach helped identify patients at higher risk of an adverse outcome who might benefit from advanced therapy. Copyright ©ERS 2015.

Time-dependent responses of rat troponin I and cardiac injury following isoproterenol administration

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Sabaheta Hasić

2011-02-01

Full Text Available Aim To develop a rat model of myocardial infarction induced by isoproterenol (ISO. We investigated a type of histological myocardial changes and cardiac troponin I (TnI kinetic. Methods The study has used adult, male, Wistar strain rats. Rats were distributed in ISO and control groups. Rats treated with ISO were divided into groups according to the time of cTnI and myocardial lesion analyses: ISO I (30’, ISO II (60’, ISO III (120’ and ISO IV (240’. We determined cTnI (Life Diagnostics Inc. West Chester PA, USA in the serum by ELISA method. We performed histological analysis on the specimens of left ventricular wall stained by hematoxillin-eosin (HE method. Results The irst statistically signiicant rise of cTnI was noted 30 minutes after the ISO administration. There was no statistically signiicant difference between cTnI mean values among the ISO groups. Observed myocardial histological changes were time dependent. Conclusions This model can be suitable for cardioprotective and cardiotoxicity supstance investigations followed by cTnI measurement in blood. The similarity between induced myocardial lesion on animal model in our study and human myocardial lesion in ischemia give us suficient impulse for further preclinical researches of new cardiac markers.

Encapsulation-Stabilized, Europium Containing Nanoparticle as a Probe for Time-Resolved luminescence Detection of Cardiac Troponin I

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Ka Ram Kim

2017-10-01

Full Text Available The use of a robust optical signaling probe with a high signal-to-noise ratio is important in the development of immunoassays. Lanthanide chelates are a promising material for this purpose, which provide time-resolved luminescence (TRL due to their large Stokes shift and long luminescence lifetime. From this, they have attracted considerable interest in the in vitro diagnostics field. However, the direct use of lanthanide chelates is limited because their luminescent signal can be easily affected by various quenchers. To overcome this drawback, strategies that rely on the entrapment of lanthanide chelates inside nanoparticles, thereby enabling the protection of the lanthanide chelate from water, have been reported. However, the poor stability of the lanthanide-entrapped nanoparticles results in a significant fluctuation in TRL signal intensity, and this still remains a challenging issue. To address this, we have developed a Lanthanide chelate-Encapsulated Silica Nano Particle (LESNP as a new immunosensing probe. In this approach, the lanthanide chelate is covalently crosslinked within the silane monomer during the silica nanoparticle formation. The resulting LESNP is physically stable and retains TRL properties of the parent lanthanide chelate. Using the probe, a highly sensitive, sandwich-based TRL immunoassay for the cardiac troponin I was conducted, exhibiting a limit of detection of 48 pg/mL. On the basis of the features of the LESNP such as TRL signaling capability, stability, and the ease of biofunctionalization, we expect that the LESNP can be widely applied in the development of TRL-based immunosensing.

Halogenated anaesthetics and cardiac protection in cardiac and non-cardiac anaesthesia

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Landoni Giovanni

2009-01-01

Full Text Available Volatile anaesthetic agents have direct protective properties against ischemic myocardial damage. The implementation of these properties during clinical anaesthesia can provide an additional tool in the treatment or prevention, or both, of ischemic cardiac dysfunction in the perioperative period. A recent meta-analysis showed that desflurane and sevoflurane reduce postoperative mortality and incidence of myocardial infarction following cardiac surgery, with significant advantages in terms of postoperative cardiac troponin release, need for inotrope support, time on mechanical ventilation, intensive care unit and overall hospital stay. Multicentre, randomised clinical trials had previously demonstrated that the use of desflurane can reduce the postoperative release of cardiac troponin I, the need for inotropic support, and the number of patients requiring prolonged hospitalisation following coronary artery bypass graft surgery either with and without cardiopulmonary bypass. The American College of Cardiology/American Heart Association Guidelines recommend volatile anaesthetic agents during non-cardiac surgery for the maintenance of general anaesthesia in patients at risk for myocardial infarction. Nonetheless, e vidence in non-coronary surgical settings is contradictory and will be reviewed in this paper together with the mechanisms of cardiac protection by volatile agents.

IN SEARCH OF THE MISSING LINK: SERUM LIPID PROFILE, TROPONIN T AND ACUTE CORONARY SYNDROME.

OpenAIRE

Basabdatta Samanta; Bharti Kawatra; Sandip

2014-01-01

Acute coronary syndrome is one of the leading causes of morbidity and mortality worldwide , hyperlipidemias being a major predisposing factor. Cardiac Troponin T (cTnT) is one of the most sensitive and specific biomarkers of myocardial injury. The aim of the study was to evaluate the relationship among TnT levels and lipid profiles of different age groups of patients with ACS , and to determine if any the association of age with lipid profile and TnT levels. The ...

Lack of concordance between a rapid bedside and conventional laboratory method of cardiac troponin testing: impact on risk stratification of patients suspected of acute coronary syndrome.

NARCIS (Netherlands)

Cramer, G.E.; Kievit, P.C.; Brouwer, M.A.; Keijzer, M.H. de; Luijten, H.E.; Verheugt, F.W.A.

2007-01-01

OBJECTIVES: This study was designed to test the usefulness of a bedside assay as compared to a laboratory method of troponin testing to predict adverse cardiac outcome of chest pain patients. METHODS: We studied 358 ER visits of patients suspected of a non ST-elevation acute coronary syndrome. cTnI

Perinatal Changes of Cardiac Troponin-I in Normal and Intrauterine Growth-Restricted Pregnancies

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Nicoletta Iacovidou

2007-01-01

Full Text Available Intrauterine growth restriction (IUGR implies fetal hypoxia, resulting in blood flow redistribution and sparing of vital organs (brain, heart. Serum cardiac Troponin-I (cTnI, a well-established marker of myocardial ischaemia, was measured in 40 mothers prior to delivery, the doubly clamped umbilical cords (representing fetal state, and their 20 IUGR and 20 appropriate-for-gestational-age (AGA neonates on day 1 and 4 postpartum. At all time points, no differences in cTnI levels were observed between the AGA and IUGR groups. Strong positive correlations were documented between maternal and fetal/neonatal values (r≥.498, P≤.025 in all cases in the AGA and r≥.615, P≤.009 in all cases in the IUGR group. These results may indicate (a normal heart function, due to heart sparing, in the IUGR group (b potential crossing of the placental barrier by cTnI in both groups

Comprehensive Characterization of Swine Cardiac Troponin T Proteoforms by Top-Down Mass Spectrometry

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Lin, Ziqing; Guo, Fang; Gregorich, Zachery R.; Sun, Ruixiang; Zhang, Han; Hu, Yang; Shanmuganayagam, Dhanansayan; Ge, Ying

2018-04-01

Cardiac troponin T (cTnT) regulates the Ca2+-mediated interaction between myosin thick filaments and actin thin filaments during cardiac contraction and relaxation. cTnT is released into the blood following injury, and increased serum levels of the protein are used clinically as a biomarker for myocardial infarction. Moreover, mutations in cTnT are causative in a number of familial cardiomyopathies. With the increasing use of large animal (swine) model to recapitulate human diseases, it is essential to characterize species-dependent protein sequence variants, alternative RNA splicing, and post-translational modifications (PTMs), but challenges remain due to the incomplete database and lack of validation of the predicted splicing isoforms. Herein, we integrated top-down mass spectrometry (MS) with online liquid chromatography (LC) and immunoaffinity purification to comprehensively characterize miniature swine cTnT proteoforms, including those arising from alternative RNA splicing and PTMs. A total of seven alternative splicing isoforms of cTnT were identified by LC/MS from swine left ventricular tissue, with each isoform containing un-phosphorylated and mono-phosphorylated proteoforms. The phosphorylation site was localized to Ser1 for the mono-phosphorylated proteoforms of cTnT1, 3, 4, and 6 by online MS/MS combining collisionally activated dissociation (CAD) and electron transfer dissociation (ETD). Offline MS/MS on Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometer with CAD and electron capture dissociation (ECD) was then utilized to achieve deep sequencing of mono-phosphorylated cTnT1 (35.2 kDa) with a high sequence coverage of 87%. Taken together, this study demonstrated the unique advantage of top-down MS in the comprehensive characterization of protein alternative splicing isoforms together with PTMs. [Figure not available: see fulltext.

Tetrodotoxin Sensitivity of the Vertebrate Cardiac Na+ Current

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Jaakko Haverinen

2011-11-01

Full Text Available Evolutionary origin and physiological significance of the tetrodotoxin (TTX resistance of the vertebrate cardiac Na+ current (INa is still unresolved. To this end, TTX sensitivity of the cardiac INa was examined in cardiac myocytes of a cyclostome (lamprey, three teleost fishes (crucian carp, burbot and rainbow trout, a clawed frog, a snake (viper and a bird (quail. In lamprey, teleost fishes, frog and bird the cardiac INa was highly TTX-sensitive with EC50-values between 1.4 and 6.6 nmol·L−1. In the snake heart, about 80% of the INa was TTX-resistant with EC50 value of 0.65 μmol·L−1, the rest being TTX-sensitive (EC50 = 0.5 nmol·L−1. Although TTX-resistance of the cardiac INa appears to be limited to mammals and reptiles, the presence of TTX-resistant isoform of Na+ channel in the lamprey heart suggest an early evolutionary origin of the TTX-resistance, perhaps in the common ancestor of all vertebrates.

Effect of radiation-induced heart injury on content of cardiac troponin I and endothelin-1 in SD rats

International Nuclear Information System (INIS)

Xu Jiuhong; Gao Yaoming; Zhang Junning; Li Xinli

2011-01-01

Objective: To investigate the effect of radiation-induced heart injury (RIHD) on cardiac endothelin-1 (ET-1) and cardiac troponin I (cTnI) in SD rats, and the possibility regarding ET-1 and cTnI as biomarker of RIHD was also explored. Methods: Healthy female SD rats were randomly divided into two groups: the control group (C) and irradiation group (R). The rats in R group were irradiated with linear accelerator at a single dose of 25 Gy. Five milliliters blood was collected from the inferior vena cava on the 5th, 15th, 30th, 60th day after radiation. Blood was centrifuged and serum was collected. Content of ET-1 and cTnI in blood serum were detected by ELISA kits. Results: The content of ET-1 in the R group was always higher than that in the C group (P<0.01) during the whole process, and the difference between two groups had statistical significance only on the 5th day (P<0.01) and 15th day (P<0.05) after radiation. However, the content of cTnI in R group was higher than that in the C group within 30 days after radiation, then decreased, and only on the 15th day (P<0.05) and the 30th day (P<0.01) after radiation, there was statistical difference between two groups. Conclusion: The content of ET-1 and cTnI in blood serum increase obviously after receiving RIHD, so these two indicators can be used as markers to diagnose early RIHD sensitively and specifically. (authors)

Evaluation of plasma sphingosine 1-phosphate, hepcidin and cardiovascular damage biomarkers (cardiac troponin I and homocysteine) in rats infected with brucellosis and vaccinated (Rev-1, RB-51).

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Azimzadeh, Kaveh; Nasrollahi Nargesabad, Reza; Vousooghi, Nasim

2017-08-01

Brucellosis is known as one of important zoonosis. Studying the histological and biochemical effects of the disease could help to increase our knowledge about it. The aim of the present study was to evaluate changes of plasma parameters after intraperitoneal injection of two species of Brucella (Brucella melitensis and Brucella abortus) and two vaccines (Rev-1, RB-51) in the rat. Forty male rats were divided into five groups (n = 8 in each group). Two groups received suspensions of Brucella abortus and Brucella melitensis and two other groups were injected intraperitoneally with two mentioned vaccines and the last group received only distilled water. The results showed a significant increase in sphingosine 1-phosphate, Malondialdehyde, hepcidin, homocysteine, cardiac troponin I and copper levels and a considerable decrease in the levels of iron and zinc (P ≤ 0.01) in infected groups compared to the control animals. In vaccinated groups, hepcidin was increased but other parameters were not changed in comparison to the control group. It can be concluded that increase of homocysteine and cardiac troponin I in brucellosis could be a warning for cardiac adverse effects. Besides, increase of sphingosine 1-phosphate probably indicates its stimulant and modulatory effects in anti- Brucellosis biochemical pathways of the host. Copyright © 2017 Elsevier Ltd. All rights reserved.

Multiplexed detection of cardiac biomarkers in serum with nanowire arrays using readout ASIC.

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Zhang, Guo-Jun; Chai, Kevin Tshun Chuan; Luo, Henry Zhan Hong; Huang, Joon Min; Tay, Ignatius Guang Kai; Lim, Andy Eu-Jin; Je, Minkyu

2012-05-15

Early detection of cardiac biomarkers for diagnosis of heart attack is the key to saving lives. Conventional method of detection like the enzyme-linked immunosorbent assay (ELISA) is time consuming and low in sensitivity. Here, we present a label-free detection system consisting of an array of silicon nanowire sensors and an interface readout application specific integrated circuit (ASIC). This system provides a rapid solution that is highly sensitive and is able to perform direct simultaneous-multiplexed detection of cardiac biomarkers in serum. Nanowire sensor arrays were demonstrated to have the required selectivity and sensitivity to perform multiplexed detection of 100 fg/ml troponin T, creatine kinase MM, and creatine kinase MB in serum. A good correlation between measurements from a probe station and the readout ASIC was obtained. Our detection system is expected to address the existing limitations in cardiac health management that are currently imposed by the conventional testing platform, and opens up possibilities in the development of a miniaturized device for point-of-care diagnostic applications. Copyright © 2012 Elsevier B.V. All rights reserved.

Combined measurement of copeptin, high-sensitivity troponin T, and N-terminal proBNP improves the identification of patients at risk of cardiovascular death

DEFF Research Database (Denmark)

Alehagen, Urban; Dahlström, Ulf; Carstensen, John

2012-01-01

and all mortality was registered. Cardiovascular mortality was evaluated using Kaplan–Meier plots and multivariate Cox proportional hazard regression analyses. Results: Copeptin, HS-TnT, and NT-proBNP measurements provided independent prognostic information in a multivariate setting over 5 years (hazard......Objectives: A multimarker strategy for the handling of patients with heart failure has been suggested in the literature. Therefore, the potential prognostic relevance of combined copeptin, high-sensitivity troponin T (HS-TnT), and N-terminal proBNP (NT-proBNP) measurement in plasma from elderly...... patients with symptoms of heart failure was evaluated. Methods: This study included 470 elderly patients (mean age 73 years) from a rural municipality with symptoms of heart failure. Clinical examination, echocardiography, and biomarker measurements were performed. All patients were followed for 13 years...

Importância da troponina-I cardíaca nos portadores de obstrução no tronco da artéria coronária esquerda sem evento cardíaco prévio Importance of cardiac troponin-I in the preoperative period of patients without prior cardiac events but suffering from left coronary branch obstruction

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Domingo M. Braile

2004-12-01

suffering from left coronary branch obstruction but without prior cardiac events. METHOD: The cardiac troponin-I serum levels of 115 patients with obstructive coronary disease were analyzed. The ages of the patients varied between 32 and 81 years old with a mean age and standard deviation of 59.7 ± 10.5 years. The patients were divided into two groups: Group A, 41 patients suffering from left coronary branch obstruction with the degree of obstruction varying between 20% to subtotal occlusion (about 60% and Group B, 74 patients without left coronary branch obstruction. All the patients were submitted to catheterism and no evidence of previous acute myocardial infarction (AMI was identified. Chemoluminescence was utilized to measure the cardiac troponin-I level using the Sanofi-Pasteur Access apparatus, with values of less than 0.l nanograms per milliliter (ng/ml considered normal. RESULTS: No association was evidenced between the degree of left coronary branch obstruction and troponin-Ic serum levels (P= 0.4617, however the average serum levels of troponin-I, in Groups A and B were 0.3841 ng/mL and 0.1711 ng/mL respectively (P=0.0324 Mann-Whitney test; OR = 4.44 95% CI 1.60 - 12.31. CONCLUSIONS: The patients of Group A have 3.44 times higher chance of presenting with myocardial injury as identified by increased cardiac troponin-I levels than Group B, independent of the degree of left coronary branch obstruction. The sensitivity of clinical suspicion of myonecrosis was relatively low (31.7%, but the specificity was high (90.5%. However the clinical importance of the documentation of myonecrosis in a determined percentage of patients with branch injury without electrocardiographic evidence is stressed. Thus, patients with left coronary branch obstruction should be quickly submitted to operative procedures, in order to avoid worsening of the myonecrosis.

Cardiac troponin T predicts occult coronary artery stenosis in patients with chronic kidney disease at the start of renal replacement therapy.

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Hayashi, Terumasa; Obi, Yoshitsugu; Kimura, Tomonori; Iio, Ken-Ichiro; Sumitsuji, Satoru; Takeda, Yoshihiro; Nagai, Yoshiyuki; Imai, Enyu

2008-09-01

The high prevalence of asymptomatic coronary artery stenosis (CAS) in chronic kidney disease (CKD) has emerged as an important predictor of outcome. However, diagnostic tools that can identify asymptomatic CAS have not yet been established. We investigated whether asymptomatic patients at the initiation of renal replacement therapy (RRT) could be screened using cardiac troponin T (cTnT) and atherosclerotic surrogate markers such as ankle-brachial blood pressure index (ABPI) and intima-media thickness (IMT). Among 142 patients who were about to start RRT, 60 who were asymptomatic underwent coronary evaluation by multi-slice computed tomography (MSCT) and/or coronary angiography (CAG). CAG diagnosed 35 patients (43.8%) as CAS positive and 27 of them had multi-vessel disease. Factors associated with CAS were smoking, elevated cTnT, low ABPI and high IMT. Moreover, the severity of CAS was associated with smoking, cTnT and ABPI. Stepwise logistic regression analyses revealed that cTnT was a powerful predictor of asymptomatic multi-vessel CAS. Receiver operating characteristic analysis documented the usefulness of cTnT as a screening tool with a cut-off point 0.05 ng/ml. The optimal screening tool for multi-vessel CAS was cTnT (sensitivity, 92.6%; 95% CI, 82.7-99.9; specificity, 63.6%; 95% CI, 47.2-80.0). We concluded that cTnT should be measured as part of a strategy for detecting asymptomatic CAS, especially multi-vessel disease in patients with CKD at the start of RRT.

Cardiac Troponin and Creatine Kinase Response to the Three Modes of Training (Running, Pedaling and Swimming in Young Girls

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Abbas Saremi

2016-04-01

Full Text Available Abstract Background: Cardiac troponin T and creatine kinase are used as biological markers for cardiomyocytes and its levels in serum are used as indicators of myocardial cell injury. The purpose of this study was to compare the effects of 3 different training protocols (runing, swimming, and pedaling training on myocardial cell injury biomarkers in young girls. Materials and Methods: In this semi-experimental study with pretest–posttest design, ten healthy young girls (aged 23.0±1.6 y were selected in a convenience sampling way. The subjects performed three types of exercise in 7 days interval. Blood sample was assessed before and after the exercise sessions. Data were analyzed using t-test and analysis of variance. Results: Our results indicated that creatin kinase increased significantly after three types of exercise (p0.05. Conclusion: Our data suggest that intensive exercise is associated with cardiac damage in less trained girls and the type of exercise is determinants of the magnitude of myocardial injury biomarkers release.

Cardiodynamicsgram: a novel tool for monitoring cardiac function in exercise training.

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Wen, Xu; Guo, Bokai; Gong, Yinglan; Xia, Ling; Yu, Jie

2018-04-27

This study evaluated the feasibility of cardiodynamicsgram (CDG) for monitoring the cardiac functions of athletes and exercisers. CDG could provide an effective, simple, and economical tool for exercise training. Seventeen middle-distance race athletes aged 14-28 years old were recruited. CDG tests and blood test including creatine kinase (CK), CK-MB isoenzyme, and high-sensitivity troponin I (hsTnI) were performed before a high-intensity prolonged training, as well as 2 and 14 h after training, respectively. The CDG test result was unsatisfactory when the CK test result was used as standard. However, the accuracy of CDG test was about 80% when CK-MB and hsTnI were used as standards. Thus, CDG offers a noninvasive, simple, and economical approach for monitoring the cardiac function of athletes and exercisers during exercise training. Nonetheless, the applicability of CDG needs further investigation.

Myocardial infarction false alarm: initial electrocardiogram and cardiac enzymes.

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Gupta, Esha Das; Sakthiswary, Rajalingham

2014-05-01

The objectives of this study were to determine the incidence of a myocardial infarction "false alarm" and evaluate the efficacy of the initial electrocardiogram and cardiac enzymes in diagnosing myocardial infarction in Malaysia. We recruited patients who were admitted with suspected myocardial infarction from June to August 2008. The medical records of these patients were reviewed for the initial electrocardiogram, initial cardiac enzyme levels (creatinine kinase-MB and troponin T), and the final diagnosis upon discharge. The subjects were stratified into 2 groups: true myocardial infarction, and false alarm. 125 patients were enrolled in this study. Following admission and further evaluation, the diagnosis was revised from myocardial infarction to other medical conditions in 48 (38.4%) patients. The sensitivity and specificity of the initial ischemic electrocardiographic changes were 54.5% and 70.8%, respectively. Raised cardiac enzymes had a sensitivity of 44.3% and specificity of 95.8%. A significant proportion of patients in Malaysia are admitted with a false-alarm myocardial infarction. The efficacy of the electrocardiogram in diagnosing myocardial infarction in Malaysia was comparable to the findings of Western studies, but the cardiac enzymes had a much lower sensitivity.

Troponin elevation in patients with various tachycardias and normal epicardial coronaries

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Yousuf Kanjwal

2008-08-01

Full Text Available Troponin elevation is usually synonymous with acute coronary syndrome (ACS. Although sensitive for ACS, the elevation of serum troponin, in the absence of clinical evidence of ischemia, should prompt a search for other etiologies of myocardial necrosis. In fact, elevated values of troponin are correlated with myocardial necrosis even though it does not discriminate the mechanism involved. We report a series of seven patients (age range 18-67 years, who presented with complaints of chest discomfort and were found to have regular supraventricular tachycardia (5 patients and one patient each with atrial fibrillation and ventricular tachycardia. All these patients had elevated troponin I and underwent coronary angiography that revealed normal epicardial coronary arteries. This is first case series in which all patients underwent coronary angiography and none of the patients was hemodynamically unstable at the time of presentation. Patients with elevated troponin due to conditions other than ACS can receive inappropriate and delayed definitive diagnosis and treatment.

Evidence of direct cardiac damage following high-intensity exercise in chronic energy restriction: A case report and literature review.

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Baird, Marianne F; Grace, Fergal; Sculthorpe, Nicholas; Graham, Scott M; Fleming, Audrey; Baker, Julien S

2017-07-01

Following prolonged endurance events such as marathons, elevated levels of cardiospecific biomarkers are commonly reported. Although transiently raised levels are generally not considered to indicate clinical myocardial damage, comprehension of this phenomenon remains incomplete. The popularity of high-intensity interval training highlights a paucity of research measuring cardiac biomarker response to this type of exercise. This a posteriori case report discusses the elevation of cardiac troponins (cTn) associated with short interval, high-intensity exercise. In this case report, an apparently healthy 29-year-old recreationally active female presented clinically raised cardiac troponin I (cTnI) levels (>0.04 ng/mL), after performing high-intensity cycle ergometer sprints. As creatine kinase (CK) is expressed by multiple organs (e.g., skeletal muscle, brain, and myocardium), cTnI assays were performed to determine any changes in total serum CK levels not originating from skeletal muscle damage. A posteriori the individual's daily energy expenditure indicated chronically low-energy availability. Psychometric testing suggested that the individual scored positive for disordered eating, highly for fatigue levels, and low in mental health components. The current case report provides novel evidence of elevated cTnI occurring as a result of performing short duration, high intensity, cycle ergometer exercise in an individual with self-reported chronically depleted energy balance. A schematic to identify potentially "at risk" individuals is presented. Considering this as a case report, results cannot be generalized; however, the main findings suggest that individuals who habitually restrict their calorie intake below their bodies' daily energy requirements, may have elevated biomarkers of exercise induced myocardial stress from performing high-intensity exercise.

Troponin elevations after non-cardiac, non-vascular surgery are predictive of major adverse cardiac events and mortality

DEFF Research Database (Denmark)

Ekeloef, S; Alamili, M; Devereaux, P J

2016-01-01

-analysis was conducted in January 2016 according to the Meta-analysis Of Observational Studies in Epidemiology guidelines. Both interventional and observational studies measuring troponin within the first 4 days after surgery were eligible. A systematic search was performed in PubMed, EMBASE, Scopus, and the Cochrane...

The naked mole-rat exhibits an unusual cardiac myofilament protein profile providing new insights into heart function of this naturally subterranean rodent.

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Grimes, Kelly M; Barefield, David Y; Kumar, Mohit; McNamara, James W; Weintraub, Susan T; de Tombe, Pieter P; Sadayappan, Sakthivel; Buffenstein, Rochelle

2017-12-01

The long-lived, hypoxic-tolerant naked mole-rat well-maintains cardiac function over its three-decade-long lifespan and exhibits many cardiac features atypical of similar-sized laboratory rodents. For example, they exhibit low heart rates and resting cardiac contractility, yet have a large cardiac reserve. These traits are considered ecophysiological adaptations to their dank subterranean atmosphere of low oxygen and high carbon dioxide levels and may also contribute to negligible declines in cardiac function during aging. We asked if naked mole-rats had a different myofilament protein signature to that of similar-sized mice that commonly show both high heart rates and high basal cardiac contractility. Adult mouse ventricles predominantly expressed α-myosin heavy chain (97.9 ± 0.4%). In contrast, and more in keeping with humans, β myosin heavy chain was the dominant isoform (79.0 ± 2.0%) in naked mole-rat ventricles. Naked mole-rat ventricles diverged from those of both humans and mice, as they expressed both cardiac and slow skeletal isoforms of troponin I. This myofilament protein profile is more commonly observed in mice in utero and during cardiomyopathies. There were no species differences in phosphorylation of cardiac myosin binding protein-C or troponin I. Phosphorylation of both ventricular myosin light chain 2 and cardiac troponin T in naked mole-rats was approximately half that observed in mice. Myofilament function was also compared between the two species using permeabilized cardiomyocytes. Together, these data suggest a cardiac myofilament protein signature that may contribute to the naked mole-rat's suite of adaptations to its natural subterranean habitat.

Using adrenaline during neonatal resuscitation may have an impact on serum cardiac troponin-T levels.

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Helmer, Caroline; Skranes, Janne H; Liestøl, Knut; Fugelseth, Drude

2015-09-01

It has been suggested that serum cardiac troponin-T (cTnT) can predict the severity of neonatal hypoxic-ischaemic encephalopathy. We evaluated whether cTnT was better correlated with adrenaline during cardiopulmonary resuscitation (CPR) than with the severity of the insult itself, based on the Apgar scores. Serum cTnT was analysed in 47 asphyxiated newborn infants treated with hypothermia. Blood samples and resuscitation data were collected from medical records, and multiple linear regressions were used to evaluate the effect of the treatment and the Apgar scores on cTnT levels. The infants were divided into three groups: the no CPR group (n = 29) just received stimulation and ventilation, the CPR minus adrenaline group (n = 9) received cardiac compression and ventilation and the CPR plus adrenaline group (n = 9) received complete CPR, including adrenaline. In the univariate analysis, the five and ten-minute Apgar scores were significantly lower in the CPR plus adrenaline group and the cTnT was significantly higher. Multiple regression analysis showed significantly higher cTnT values in the CPR plus adrenaline group, but no significant relationship between cTnT and the Apgar scores. Although cTnT correlated with the severity of the insult in neonatal hypoxic-ischaemic encephalopathy, the levels may have been affected by adrenaline administered during CPR. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Safety and efficacy of high-dose melphalan and auto-SCT in patients with AL amyloidosis and cardiac involvement.

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Girnius, S; Seldin, D C; Meier-Ewert, H K; Sloan, J M; Quillen, K; Ruberg, F L; Berk, J L; Doros, G; Sanchorawala, V

2014-03-01

In Ig light chain (AL) amyloidosis, cardiac involvement is associated with worse prognosis and increased treatment-related complications. In this retrospective cohort study, we assessed survival, hematologic and cardiac responses to high-dose melphalan and auto-SCT (HDM/SCT) in patients with AL amyloidosis and cardiac involvement, stratified by cardiac biomarkers brain natriuretic peptide and Troponin I, analogous to the Mayo cardiac staging. Forty-seven patients underwent HDM/SCT based upon functional measures; six patients had modified cardiac stage I disease, seventeen had modified cardiac stage II disease and twenty-four had modified cardiac stage III disease. Treatment-related mortality was 4% for all patients and 8% for patients with stage III disease. Three-year survival was 88% and EFS was 47%; these did not differ by stage. By intention-to-treat analysis, 27% of patients achieved a hematologic complete response and 32% a very good partial response, of whom 70 and 45%, respectively, have not required additional therapy at 36 months. Cardiac response was achieved in 53% of patients. We conclude that with appropriate patient selection and a risk-adapted treatment approach, HDM/SCT is safe and effective in patients with AL amyloidosis and cardiac involvement.

The value of determination of blood cardiac troponin T, IL-8 and TNF-α contents for the diagnosis and prognosis assessment in patients with viral myocarditis

International Nuclear Information System (INIS)

Tao Qian; Zhou Xuanyan; Li Enjie

2006-01-01

Objective: To investigate the value of determination of blood cardiac troponin T (cTnT), IL-8 and TNF-α contents for the diagnosis and prognosis assessment in patients with viral myocarditis (VMC). Methods: Plasma cTnT (with immuno-infiltration method) and serum IL - 8, TNF ( with ELISA) contents were measured in 86 patients with VMC at different stages ( 1 months, 6 months), and 30 controls. Results: The positive rates of blood cTnT, IL-8 and TNF-α in acute VMC patients were significantly higher than those in patients with history less than 6 months as well as with history more than 6 months and the controls group (P 0.05). The cure rate in patients with positive cTnT was significantly lower than that in patients with negative cTnT both at 1 months and 6 months (P<0.005). Conclusion: Blood cTnT, IL-8 and TNF-α are sensitive and specific predictors for diagnosis and prognosis assessment in patients with VMC. (authors)

Chronic defensiveness and neuroendocrine dysfunction reflect a novel cardiac troponin T cut point: The SABPA study.

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Malan, Leoné; Hamer, Mark; von Känel, Roland; Lambert, Gavin W; Delport, Rhena; Steyn, Hendrik S; Malan, Nicolaas T

2017-11-01

Sympatho-adrenal responses are activated as an innate defense coping (DefS) mechanism during emotional stress. Whether these sympatho-adrenal responses drive cardiac troponin T (cTnT) increases are unknown. Therefore, associations between cTnT and sympatho-adrenal responses were assessed. A prospective bi-ethnic cohort, excluding atrial fibrillation, myocardial infarction and stroke cases, was followed for 3 years (N=342; 45.6±9.0years). We obtained serum high-sensitive cTnT and exposure measures [Coping-Strategy-Indicator, depression/Patient-Health-Questionnarie-9, 24h BP, 24h heart-rate-variability (HRV) and 24h urinary catecholamines]. Blacks showed moderate depression (45% vs. 16%) and 24h hypertension (67% vs. 42%) prevalence compared to Whites. A receiver-operating-characteristics cTnT cut-point 4.2ng/L predicting hypertension in Blacks was used as binary outcome measure in relation to exposure measures [AUC 0.68 (95% CI 0.60-0.76); sensitivity/specificity 63/70%; P≤0.001]. Bi-ethnic cTnT-incidence was similar (Blacks=27%, Whites=25%) with cTnT-recovery better in Blacks (9%) compared to Whites (5%), P=0.001. In cross-sectional analyses, elevated cTnT was related to DefS [OR 1.08 (95% CI 0.99-1.16); P=0.06]; 24h BP [OR 1.03-1.04 (95% CI 1.01-1.08); P≤0.02] and depressed HRV [OR 2.19 (95% CI 1.09-4.41); P=0.03] in Blacks, but not in Whites. At 3year follow-up, elevated cTnT was related to attenuated urine norepinephrine:creatinine ratio in Blacks [OR 1.46 (95% CI 1.01-2.10); P=0.04]. In Whites, a cut point of 5.6ng/L cTnT predicting hypertension was not associated with exposure measures. Central neural control systems exemplified a brain-heart stress pathway. Desensitization of sympatho-adrenal responses occurred with initial neural- (HRV) followed by neuroendocrine dysfunction (norepinephrine:creatinine) in relation to elevated cTnT. Chronic defensiveness may thus drive the desensitization or physiological depression, reflecting ischemic heart disease

Troponin rise in hospitalized patients with nonacute coronary syndrome: retrospective assessment of outcomes and predictors.

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Dhesi, Sumandeep; Shanks, Miriam; Tymchak, Wayne J

2015-03-01

Cardiac troponin is elevated in several clinical settings apart from thrombotic acute coronary syndrome (ACS) and is associated with increased adverse events. It is not clear whether troponin elevation in type II myocardial infarction (MI) is associated with increased cardiovascular events. Our objectives were to identify the cause of mortality in type II MI and to attempt to establish the threshold range of cardiac troponin-I (cTnI) elevation as well as clinical factors associated with adverse outcomes in type II MI. This retrospective cohort study included 245 patients presenting with a noncardiac primary diagnosis associated with cTnI elevation at a single centre from January 2003 to December 2011. Primary outcome was a composite of cardiovascular and noncardiovascular mortality. Secondary outcomes included subsequent stroke, ACS, and heart failure (HF). At 1 year, ACS occurred in 13 patients (5.3%), stroke was seen in 10 (4.1%) patients, and HF occurred in 19 (7.8%) patients. Overall 1-year mortality included 102 events (41.6%), with 10 cardiovascular deaths (9.8%), 65 noncardiovascular deaths (63.7%), and 27 (26.5%) deaths from unknown causes. In multivariable analysis, factors independently associated with increased overall 1-year mortality included cTnI elevation ≥ 4.63 μg/L (odds ratio [OR], 3.37; 95% confidence interval [CI], 1.55-7.34; P = 0.002), age ≥ 70 years (OR, 2.44; 95% CI, 1.40-4.29; P = 0.002), and estimated glomerular filtration rate high after type II MI, the majority of mortality is caused by noncardiovascular events. Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Investigating the role of uncoupling of Troponin I phosphorylation from changes in myofibrillar Ca2+-sensitivity in the pathogenesis of Cardiomyopathy

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Andrew Easton Messer

2014-08-01

Full Text Available Contraction in the mammalian heart is controlled by the intracellular Ca2+ concentration as it is in all striated muscle, but the heart has an additional signalling system that comes into play to increase heart rate and cardiac output during exercise or stress. β-adrenergic stimulation of heart muscle cells leads to release of cyclic-AMP and the activation of protein kinase A which phosphorylates key proteins in the sarcolemma, sarcoplasmic reticulum and contractile apparatus. Troponin I (TnI and Myosin Binding Protein C (MyBP-C are the prime targets in the myofilaments. TnI phosphorylation lowers myofibrillar Ca2+-sensitivity and increases the speed of Ca2+-dissociation and relaxation (lusitropic effect.Recent studies have shown that this relationship between Ca2+-sensitivity and TnI phosphorylation may be unstable. In familial cardiomyopathies, both dilated and hypertrophic (DCM and HCM, a mutation in one of the proteins of the thin filament often results in the loss of the relationship (uncoupling and blunting of the lusitropic response. For familial dilated cardiomyopathy in thin filament proteins it has been proposed that this uncoupling is causative of the phenotype. Uncoupling has also been found in human heart tissue from patients with hypertrophic obstructive cardiomyopathy as a secondary effect. Recently, it has been found that Ca2+-sensitizing drugs can promote uncoupling, whilst one Ca2+-desensitising drug Epigallocatechin 3-Gallate (EGCG can reverse uncoupling.We will discuss recent findings about the role of uncoupling in the development of cardiomyopathies and the molecular mechanism of the process.

St. Dominic Savio Nursing Home, Cahilly, Liscannor, Clare.

LENUS (Irish Health Repository)

Lee, Graham R

2016-04-01

High sensitivity cardiac troponin T and I (hs-cTnT and hs-cTnI) assays show analytical, diagnostic and prognostic improvement over contemporary sensitive cTn assays. However, given the importance of troponin in the diagnosis of myocardial infarction, implementing this test requires rigorous analytical and clinical verification across the total testing pathway. This was the aim of this study.

Cardiac troponin and tropomyosin: structural and cellular perspectives to unveil the Hypertrophic Cardiomyopathy phenotype

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Mayra de A. Marques

2016-09-01

Full Text Available Inherited myopathies affect both skeletal and cardiac muscle and are commonly associated with genetic dysfunctions, leading to the production of anomalous proteins. In cardiomyopathies, mutations frequently occur in sarcomeric genes, but the cause-effect scenario between genetic alterations and pathological processes remains elusive. Hypertrophic cardiomyopathy (HCM was the first cardiac disease associated with a genetic background. Since the discovery of the first mutation in the β-myosin heavy chain, more than 1,400 new mutations in 11 sarcomeric genes have been reported, awarding HCM the title of the disease of the sarcomere. The most common macroscopic phenotypes are left ventricle and interventricular septal thickening, but because the clinical profile of this disease is quite heterogeneous, these phenotypes are not suitable for an accurate diagnosis. The development of genomic approaches for clinical investigation allows for diagnostic progress and understanding at the molecular level. Meanwhile, the lack of accurate in vivo models to better comprehend the cellular events triggered by this pathology has become a challenge. Notwithstanding, the imbalance of Ca2+ concentrations, altered signaling pathways, induction of apoptotic factors, and heart remodeling leading to abnormal anatomy have already been reported. Of note, a misbalance of signaling biomolecules, such as kinases and tumor suppressors (e.g., Akt and p53, seems to participate in apoptotic and fibrotic events. In HCM, structural and cellular information about defective sarcomeric proteins and their altered interactome is emerging but still represents a bottleneck for developing new concepts in basic research and for future therapeutic interventions. This review focuses on the structural and cellular alterations triggered by HCM-causing mutations in troponin and tropomyosin proteins and how structural biology can aid in the discovery of new platforms for therapeutics. We

Cardiac troponin I degradation in serum of patients with hypertrophic obstructive cardiomyopathy undergoing percutaneous septal ablation

DEFF Research Database (Denmark)

Madsen, Lene H; Lund, Terje; Grieg, Zanina

2009-01-01

prior to initiation of PTSMA and up to 50 h following the procedure. Western blot analysis was performed with subsequent analysis of relative intensities of the bands as compared to the degradation of cTnI in STEMI patients from the ASSENT-2 troponin substudy. RESULTS: We demonstrate intact cTnI and 9...... degradation products [molecular weight (MW) 12.0-23.5 kDa]. The bands were comparable in MW to degradation fragments in STEMI. Their early rise in intensity, occurring within few minutes after the alcohol injection, emphasizes how susceptible troponin bands are to chemical/ischemic insults. Moreover, two...... additional bands were visible in the PTSMA population. CONCLUSION: This work describes the degradation products of troponin I in HOCM patients undergoing PTSMA. The detected bands appear fast and are similar to degradations following STEMI. This model contributes to our knowledge of the degradation patterns...

The structure of the muscle protein complex 4Ca2+ ·troponin C · troponin

International Nuclear Information System (INIS)

Olah, G.A.; Trewhella, J.

1994-01-01

Analysis of scattering data based on a Monte Carlo integration method was used to 2+ obtain a low resolution model of the 4Ca 2+ circ troponin C circ troponin I complex. This modeling method allows rapid testing of plausible structures where the best fit model can be ascertained by a comparison between model structure scattering profiles and measured scattering data. In the best fit model, troponin I appears as a spiral structure 2+ that wraps around 4Ca 2+ circ troponin C which adopts an extended dumbbell conformation similar to that observed in the crystal structures of troponin C. The Monte Carlo modeling method can be applied to other biological systems in which detailed structural information is lacking

Electrocardiographic Findings and Serum Troponin I in Carbon Monoxide Poisoned Patients

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Scott Reza Jafarian Kerman

2012-03-01

Full Text Available Carbon monoxide (CO poisoning, though with different sources, is one of the most deadly emergencies in all countries. CO can threaten men's life by several paths especially cardiac complications, which can mimic other cardiac problems such as myocardial infarction. The objective of this study was to determine ECG findings and serum troponin I levels in CO poisoned patients. In this analytical cross-sectional study, 63 CO poisoning patients were consecutively included from hospital's emergency departments. CO content was measured by a CO-oximeter and an electrocardiography was taken first thing on admission. Arterial blood gas (ABG, troponin I and other data was collected afterwards. Data were divided by age groups (adults and children and gender. CO content was significantly higher only in subjects with normal T wave compared to patients with inverted T wave in their initial ECG (P=0.016. No other significant difference was noticed. None of the ABG findings correlated significantly with CO content. Also no significant correlation was found with CO content after stratification by gender and age groups, but pH in children (r=-0.484, P=0.026. CO content was significantly higher in adults (P=0.023, but other ABG data were not significantly different. Only 3 patients had elevated troponin I. Receiver operating characteristic (ROC analysis showed no significant cutoff points in CO content for ECG changes. No significant specific change in electrocardiograms (ECG could contribute carboxyhemoglobin content in carbon monoxide poisoned patients. In addition, no specific difference was found between adults and pediatric subjects' ECGs. All other findings seemed to be accidental.

Serial Measurement of High-Sensitivity Troponin I and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus in the EXAMINE Trial (Examination of Cardiovascular Outcomes With Alogliptin Versus Standard of Care).

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Cavender, Matthew A; White, William B; Jarolim, Petr; Bakris, George L; Cushman, William C; Kupfer, Stuart; Gao, Qi; Mehta, Cyrus R; Zannad, Faiez; Cannon, Christopher P; Morrow, David A

2017-05-16

We aimed to describe the relationship between changes in high-sensitivity cardiac troponin I (hsTnI) and cardiovascular outcomes. The EXAMINE trial (Examination of Cardiovascular Outcomes With Alogliptin Versus Standard of Care) was a phase IIIb clinical outcomes trial designed to evaluate the cardiovascular safety of alogliptin, a nonselective dipeptidyl peptidase 4 inhibitor. Patients with type 2 diabetes mellitus, glycohemoglobin between 6.5% and 11% (or between 7% and 11% if they were on insulin), and a recent acute coronary syndrome (between 15 and 90 days before randomization) were eligible for the trial. hsTnI was measured using the Abbott ARCHITECT assay at baseline and 6 months in patients randomized in the EXAMINE trial. This analysis was restricted to patients randomized ≥30 days after qualifying acute coronary syndrome to mitigate the potential for persistent hsTnI elevation after acute coronary syndrome (n=3808). The primary end point of the trial was cardiovascular death, myocardial infarction, or stroke. Cardiovascular death or heart failure was a prespecified, adjudicated secondary end point. At baseline, hsTnI was detectable (≥1.9 ng/L) in 93% of patients and >99 th percentile upper reference limit in 16%. There was a strong relationship between increasing hsTnI, both at baseline and 6 months, and the incidence of cardiovascular events through 24 months ( P diabetes mellitus without clinically recognized events had dynamic or persistently elevated values and were at high risk of recurrent events. hsTnI may have a role in personalizing preventive strategies in patients with diabetes mellitus based on risk. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00968708. © 2017 American Heart Association, Inc.

Influence of the cardiac glycoside digoxin on cardiac troponin I, acid-base and electrolyte balance, and haematobiochemical profiles in healthy donkeys (Equus asinus).

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Tharwat, Mohamed; Al-Sobayil, Fahd

2014-03-12

The effect of digoxin administration on the serum concentration of the cardiac troponin I (cTnI) has not been reported to date in equidae. This study was therefore designed to evaluate the effect of digoxin on cardiac cell damage in donkeys (Equus asinus) as assessed by cTnI, acid-base and electrolyte balance and haematobiochemical profiles. Ten clinically healthy donkeys were given an IV infusion of digoxin at a dose of 14 μg/kg. Blood samples were collected from the donkeys up through 72 h post-injection. Three of the donkeys exhibited increased heart and respiratory rates post-injection. In the other seven animals, the heart and respiratory rates were lower 4 h post-injection. The serum digoxin concentration increased significantly at many time points after injection. The serum concentration of cTnI did not differ significantly between pre- and post-injection. An increase in blood pH was noted at 3 h after digoxin injection. There were also increases in PO2 and in oxygen saturation. Decreases in PCO2 at 2 to 48 h post-injection as well as a decrease in blood lactate at 4 h post-injection were observed. The serum concentration of glucose remained significantly elevated at all-time points after digoxin injection. It is concluded that administration of digoxin to healthy donkeys (14 μg/kg) did not result in elevations of serum cTnI concentration, signs of digoxin intoxication, ECG abnormalities and did not increase serum concentrations of blood urea nitrogen and creatinine.

Nanocomposites of gold nanoparticles and graphene oxide towards an stable label-free electrochemical immunosensor for detection of cardiac marker troponin-I

International Nuclear Information System (INIS)

Liu, Guozhen; Qi, Meng; Zhang, Yin; Cao, Chaomin; Goldys, Ewa M.

2016-01-01

A stable label-free amperometric immunosensor is presented based on gold nanoparticles and graphene oxide nanocomposites for detection of cardiac troponin-I in the early diagnosis of myocardial infarction. For designing of the sensing platform, firstly the nanocomposites based on GO and AuNPs were prepared and anchored on electrode surfaces. The formed nanocomposites provided a platform with big surface area for loading anti-cTnI capture antibody, and worked as a bridge for fast electron transfer subsequently increased the sensitivity. Moreover, the linkages between AuNP, GO, and electrodes were based on covalent bonding by aryldiazonium salt coupling chemistry, which favors the stability of the sensing interface. Finally, the anti-cTnI detection antibody was immobilized on GO tailored with ferrocene molecules, functioning as the signal reporter for the detection of cTnI. The modification process was monitored using electrochemistry, SEM, XPS. The herein immunosensor demonstrates a good selectivity and high sensitivity against human-cTnI, and is capable of detecting cTnI at concentrations as low as 0.05 ng mL −1 , which is 100 times lower than that possible by conventional methods. It is potential to design the portable sensing platform based on AuNPs and GO nanocomposites for future point-of-care diagnostics. - Highlights: • Nanocomposites based on GO and AuNPs were prepared and anchored on the electrode surfaces covalently to form a stable sensing interface. • The anti-cTnI detection antibody was immobilized on GO tailored with ferrocene molecules, functioning as the signal reporter for the detection of cTnI. • The detectable concentration of cTnI is 0.05 ng mL -1 in buffer with the assay time of less than 5 min. • The herein simple and novel approach for fabrication of AuNP and graphene based platform is promising for future fabrication of point-of-care devices.

Cardiac biomarkers in Neonatology

OpenAIRE

Vijlbrief, D.C.

2015-01-01

In this thesis, the role for cardiac biomarkers in neonatology was investigated. Several clinically relevant results were reported. In term and preterm infants, hypoxia and subsequent adaptation play an important role in cardiac biomarker elevation. The elevated natriuretic peptides are indicative of abnormal function; elevated troponins are suggestive for cardiomyocyte damage. This methodology makes these biomarkers of additional value in the treatment of newborn infants, separate or as a co...

Troponin T and NT ProBNP Levels in Gestational, Type 1 and Type 2 Diabetic Mothers and Macrosomic Infants.

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Mert, Mustafa Kurthan; Satar, Mehmet; Özbarlas, Nazan; Yaman, Akgün; Özgünen, Fatma Tuncay; Asker, Hüseyin Selim; Çekinmez, Eren Kale; Tetiker, Tamer

2016-01-01

This study compares NT proBNP and troponin T levels in umbilical cord arterial blood and postnatal echocardiographic findings for infants of gestational and pregestational diabetic mothers and macrosomic infants. Twenty-seven infants of pregestational diabetic mothers, 61 infants of gestational diabetic mothers and 37 macrosomic infants of nondiabetic mothers were prospectively enrolled in this study along with a control group of 58 healthy infants of mothers without any pregestational or gestational disorders as the control group. All enrollees were born after 34 weeks of gestation. For this study, umbilical cord blood was drawn during delivery to determine NT proBNP and troponin T levels. Echocardiography was performed 24-72 h after the delivery. Umbilical cord troponin T and NT proBNP levels were found to be higher in the diabetic and macrosomic groups than in the control group (all of them p gestational infants of diabetic mothers groups (r = 0.564 and r = 0.560, respectively, p gestational diabetic mothers were divided into two groups according to HbA1c levels in the third trimester as good (6.1 %) metabolic control. In the good and suboptimal metabolic control diabetic groups, NT proBNP levels were also positively correlated with interventricular septum thickness (r = 0.536 and r = 0.576, respectively, p mothers and the control group, the myocardial performance index of macrosomic infants was lower than that of the control group (p = 0.017). Cardiac biomarkers (NT proBNP and troponin T) were elevated in infants of diabetic mothers and macrosomic infants. While there was a positive correlation between NT proBNP levels and cardiac structure in infants of pregestational and gestational diabetic mothers, there was no relationship between NT proBNP levels and cardiac function.

Cardiac troponin-I on diagnosis predicts early death and refractoriness in acquired thrombotic thrombocytopenic purpura. Experience of the French Thrombotic Microangiopathies Reference Center.

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Benhamou, Y; Boelle, P-Y; Baudin, B; Ederhy, S; Gras, J; Galicier, L; Azoulay, E; Provôt, F; Maury, E; Pène, F; Mira, J-P; Wynckel, A; Presne, C; Poullin, P; Halimi, J-M; Delmas, Y; Kanouni, T; Seguin, A; Mousson, C; Servais, A; Bordessoule, D; Perez, P; Hamidou, M; Cohen, A; Veyradier, A; Coppo, P

2015-02-01

Cardiac involvement is a major cause of mortality in patients with thrombotic thrombocytopenic purpura (TTP). However, diagnosis remains underestimated and delayed, owing to subclinical injuries. Cardiac troponin-I measurement (cTnI) on admission could improve the early diagnosis of cardiac involvement and have prognostic value. To assess the predictive value of cTnI in patients with TTP for death or refractoriness. The study involved a prospective cohort of adult TTP patients with acquired severe ADAMTS-13 deficiency ( 0.1 μg L(-1) ) was present in 78 patients (59%), of whom 46 (59%) had no clinical cardiac involvement. The main outcomes were death (25%) and refractoriness (17%). Age (P = 0.02) and cTnI level (P = 0.002) showed the greatest impact on survival. A cTnI level of > 0.25 μg L(-1) was the only independent factor in predicting death (odds ratio [OR] 2.87; 95% confidence interval [CI] 1.13-7.22; P = 0.024) and/or refractoriness (OR 3.03; 95% CI 1.27-7.3; P = 0.01). A CTnI level of > 0.25 μg L(-1) at presentation in patients with TTP appears to be an independent factor associated with a three-fold increase in the risk of death or refractoriness. Therefore, cTnI level should be considered as a prognostic indicator in patients diagnosed with TTP. © 2014 International Society on Thrombosis and Haemostasis.

Incremental value of a combination of cardiac troponin T, N-terminal pro-brain natriuretic peptide and C-reactive protein for prediction of mortality in end-stage renal disease

DEFF Research Database (Denmark)

Hallén, Jonas; Madsen, Lene Helleskov; Ladefoged, Søren

2011-01-01

Abstract Objective. To determine the relative prognostic merits of C-reactive protein (CRP), cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) for prediction of all-cause death in patients with end-stage renal disease (ESRD) receiving haemodialysis. Material...... and methods. This prospective, controlled cohort study included 109 patients. Biomarkers were sampled at inclusion and considered as categorical and continuous variables in Cox proportional hazard models. Results. Mean follow-up ± SD was 926 ± 385 days, during which 52 patients (48%) died. All three markers...

Association of elevated serum cardiac troponin-I level and complications in acute heart failurecases

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Farjana Akhter

2013-07-01

Full Text Available Acute heart failure is one of the major causes of morbidity and mortality all over the world. Available published data has suggested that patients of acute heart failure with elevated level of serum cardiac troponin-I (cTn-I have more adverse outcomes than that of acute heart failure with normal cTn-I level. Elevated level of serum cTn-I is a potential risk factor for acute heart failure. This study was carried out in the department of Biochemistry, Dhaka Medical College and National Institute of Cardiovascular Disease (NICVD during the period from January 2010 to December 2010. In this study, 100 patients with acute heart failure were enrolled. Out of 100 cases, 50 had elevated serum cTn-I (cTn-I ³ 1.0 ng/ml and 50 had normal serum cTn-I (cTn-I < 1.0 ng/ml. The adverse outcome of the two groups were recorded and compared. Patients with high and normal serum cTn-I had mean age of 52.40 ± 8.10 years and 54.64 ± 7.26 years respectively while male and female cases were equally distributed. Left ventricular systolic dysfunction (lower ejection fraction was significantly (p<0.05 higher among cases with elevated cTn-I level compared to those with normal level. The rate of renal failure (raised serum creatinine, impaired liver functions (raised ALT and AST and abnormal serum electrolytes were significantly higher among the patients with elevated cTn-I compared to those with normal level. The study showed that elevated serum cTn-I level was a good biomarker to indicate adverse complications in acute heart failure cases. Ibrahim Med. Coll. J. 2013; 7(2: 32-34

Role of Admission Troponin-T and Serial Troponin-T Testing in Predicting Outcomes in Severe Sepsis and Septic Shock.

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Vallabhajosyula, Saraschandra; Sakhuja, Ankit; Geske, Jeffrey B; Kumar, Mukesh; Poterucha, Joseph T; Kashyap, Rahul; Kashani, Kianoush; Jaffe, Allan S; Jentzer, Jacob C

2017-09-09

Troponin-T elevation is seen commonly in sepsis and septic shock patients admitted to the intensive care unit. We sought to evaluate the role of admission and serial troponin-T testing in the prognostication of these patients. This was a retrospective cohort study from 2007 to 2014 on patients admitted to the intensive care units at the Mayo Clinic with severe sepsis and septic shock. Elevated admission troponin-T and significant delta troponin-T were defined as ≥0.01 ng/mL and ≥0.03 ng/mL in 3 hours, respectively. The primary outcome was in-hospital mortality. Secondary outcomes included 1-year mortality and lengths of stay. During this 8-year period, 944 patients met the inclusion criteria with 845 (90%) having an admission troponin-T ≥0.01 ng/mL. Serial troponin-T values were available in 732 (78%) patients. Elevated admission troponin-T was associated with older age, higher baseline comorbidity, and severity of illness, whereas significant delta troponin-T was associated with higher severity of illness. Admission log 10 troponin-T was associated with unadjusted in-hospital (odds ratio 1.6; P =0.003) and 1-year mortality (odds ratio 1.3; P =0.04), but did not correlate with length of stay. Elevated delta troponin-T and log 10 delta troponin-T were not significantly associated with any of the primary or secondary outcomes. Admission log 10 troponin-T remained an independent predictor of in-hospital mortality (odds ratio 1.4; P =0.04) and 1-year survival (hazard ratio 1.3; P =0.008). In patients with sepsis and septic shock, elevated admission troponin-T was associated with higher short- and long-term mortality. Routine serial troponin-T testing did not add incremental prognostic value in these patients. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Myofilament Calcium Sensitivity: Mechanistic Insight into TnI Ser-23/24 and Ser-150 Phosphorylation Integration

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Hussam E Salhi

2016-12-01

Full Text Available Troponin I (TnI is a major regulator of cardiac muscle contraction and relaxation. During physiological and pathological stress, TnI is differentially phosphorylated at multiple residues through different signaling pathways to match cardiac function to demand. The combination of these TnI phosphorylations can exhibit an expected or unexpected functional integration, whereby the function of two phosphorylations are different than that predicted from the combined function of each individual phosphorylation alone. We have shown that TnI Ser-23/24 and Ser-150 phosphorylation exhibit functional integration and are simultaneously increased in response to cardiac stress. In the current study, we investigated the functional integration of TnI Ser-23/24 and Ser-150 to alter cardiac contraction. We hypothesized that Ser-23/24 and Ser-150 phosphorylation each utilize distinct molecular mechanisms to alter the TnI binding affinity within the thin filament. Mathematical modeling predicts that Ser-23/24 and Ser-150 phosphorylation affect different TnI affinities within the thin filament to distinctly alter the Ca2+-binding properties of troponin. Protein binding experiments validate this assertion by demonstrating pseudo-phosphorylated Ser-150 decreases the affinity of isolated TnI for actin, whereas Ser-23/24 pseudo-phosphorylation is not different from unphosphorylated. Thus, our data supports that TnI Ser-23/24 affects TnI-TnC binding, while Ser-150 phosphorylation alters TnI-actin binding. By measuring force development in troponin-exchanged skinned myocytes, we demonstrate that the Ca2+ sensitivity of force is directly related to the amount of phosphate present on TnI. Furthermore, we demonstrate that Ser-150 pseudo-phosphorylation blunts Ser-23/24-mediated decreased Ca2+-sensitive force development whether on the same or different TnI molecule. Therefore, TnI phosphorylations can integrate across troponins along the myofilament. These data demonstrate

Measurement of cardiac troponin I utilizing a point of care analyzer in healthy alpacas.

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Blass, Keith A; Kraus, Marc S; Rishniw, Mark; Mann, Sabine; Mitchell, Lisa M; Divers, Thomas J

2011-12-01

Myocardial disease in camelids is poorly characterized. Nutritional (selenium deficiency) and toxic (ionophore toxicity) myocardial disease have been reported in camelids. Diagnosis and management of these and other myocardial diseases might be enhanced by evaluating cardiac troponin I (cTnI) concentrations. No information about cTnI reference intervals in camelids is currently available. (A) To determine cTnI concentrations obtained using a point of care i-STAT(®)1 analyzer (Heska Corporation) in healthy alpacas; (B) to compare alpaca cTnI concentrations between heparinized whole blood and plasma samples and between 2 different storage conditions (4 °C for 24 h or -80 °C for 30 days); (C) to examine assay reproducibility using the i-STAT(®)1. 23 healthy alpacas were evaluated. Blood and plasma samples were analyzed by the i-STAT(®)1 within 1 h of collection. Aliquots of plasma were stored at either 4 °C for 24 h or -80 °C for 30 days, and then analyzed. Assay reproducibility was determined by comparing 2 plasma or whole blood cTnI concentrations measured on the same sample over a 10 min period. Analyzer-specific plasma cTnI concentrations in clinically normal alpacas had a median of blood concentrations showed good agreement. Storage did not affect cTnI concentrations (p > 0.75). Plasma cTnI concentrations had coefficient of repeatability of 0.02 ng/mL. The i-STAT(®)1 can measure cTnI in alpacas on both plasma and whole blood and provides similar values for both samples. Storage at 4 °C for 24 h or -80 °C for 30 days does not affect estimates of plasma cTnI. Evaluation of cTnI might be of value in assessing cardiac disease in this species. Copyright © 2011 Elsevier B.V. All rights reserved.

The R21C Mutation in Cardiac Troponin I Imposes Differences in Contractile Force Generation between the Left and Right Ventricles of Knock-In Mice

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Jingsheng Liang

2015-01-01

Full Text Available We investigated the effect of the hypertrophic cardiomyopathy-linked R21C (arginine to cysteine mutation in human cardiac troponin I (cTnI on the contractile properties and myofilament protein phosphorylation in papillary muscle preparations from left (LV and right (RV ventricles of homozygous R21C+/+ knock-in mice. The maximal steady-state force was significantly reduced in skinned papillary muscle strips from the LV compared to RV, with the latter displaying the level of force observed in LV or RV from wild-type (WT mice. There were no differences in the Ca2+ sensitivity between the RV and LV of R21C+/+ mice; however, the Ca2+ sensitivity of force was higher in RV-R21C+/+ compared with RV-WT and lower in LV- R21C+/+ compared with LV-WT. We also observed partial loss of Ca2+ regulation at low [Ca2+]. In addition, R21C+/+-KI hearts showed no Ser23/24-cTnI phosphorylation compared to LV or RV of WT mice. However, phosphorylation of the myosin regulatory light chain (RLC was significantly higher in the RV versus LV of R21C+/+ mice and versus LV and RV of WT mice. The difference in RLC phosphorylation between the ventricles of R21C+/+ mice likely contributes to observed differences in contractile force and the lower tension monitored in the LV of HCM mice.

Evaluation of microRNAs − 208 and 133a/b as differential biomarkers of acute cardiac and skeletal muscle toxicity in rats

Energy Technology Data Exchange (ETDEWEB)

Calvano, Jacqueline, E-mail: Jacqueline.Calvano@bms.com [Drug Safety Evaluation, Bristol-Myers Squibb, 1 Squibb Drive, New Brunswick, NJ 08903 (United States); Achanzar, William; Murphy, Bethanne [Drug Safety Evaluation, Bristol-Myers Squibb, 1 Squibb Drive, New Brunswick, NJ 08903 (United States); DiPiero, Janet [Discovery Toxicology, Bristol-Myers Squibb, Route 206 and Province Line Road, Lawrenceville, NJ 08540 (United States); Hixson, Clifford; Parrula, Cecilia; Burr, Holly; Mangipudy, Raja; Tirmenstein, Mark [Drug Safety Evaluation, Bristol-Myers Squibb, 1 Squibb Drive, New Brunswick, NJ 08903 (United States)

2016-12-01

Conventional circulating biomarkers of cardiac and skeletal muscle (SKM) toxicity lack specificity and/or have a short half-life. MicroRNAs (miRNAs) are currently being assessed as biomarkers of tissue injury based on their long half-life in blood and selective expression in certain tissues. To assess the utility of miRNAs as biomarkers of cardiac and SKM injury, male Sprague–Dawley rats received a single dose of isoproterenol (ISO); metaproterenol (MET); allylamine (AAM); mitoxantrone (MIT); acetaminophen (APAP) or vehicle. Blood and tissues were collected from rats in each group at 4, 24 and 48 h. ISO, MET, and AAM induced cardiac and SKM lesions and APAP induced liver specific lesions. There was no evidence of tissue injury with MIT by histopathology. Serum levels of candidate miRNAs were compared to conventional serum biomarkers of SKM/cardiac toxicity. Increases in heart specific miR-208 only occurred in rats with cardiac lesions alone and were increased for a longer duration than cardiac troponin and FABP3 (cardiac biomarkers). ISO, MET and AAM induced increases in MyL3 and skeletal muscle troponin (sTnl) (SKM biomarkers). MIT induced large increases in sTnl indicative of SKM toxicity, but sTnl levels were also increased in APAP-treated rats that lacked SKM toxicity. Serum levels of miR-133a/b (enriched in cardiac and SKM) increased following ISO, MET, AAM and MIT treatments but were absent in APAP-treated rats. Our results suggest that miR-133a/b are sensitive and specific markers of SKM and cardiac toxicity and that miR-208 used in combination with miR-133a/b can be used to differentiate cardiac from SKM toxicity. - Highlights: • MiR-208 is specifically expressed in rat hearts. • MiR-133a/b are enriched in rat cardiac/skeletal muscle. • MiR-133a/b are sensitive and specific markers of muscle/cardiac toxicity. • MiR-208 can be used to differentiate cardiac toxicity from skeletal muscle toxicity.

COMPARISON OF CARDIAC BIOMARKERS AND ECHOCARDIOGRAPHY IN DIAGNOSING MYOCARDITIS

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Nimi Bharathan

2017-03-01

Full Text Available BACKGROUND Conventional methods used to diagnose or rule out myocarditis is not useful in detecting cardiac myocyte injury in clinically suspected cases. Endomyocardial biopsy and histopathological examination is not feasible in most government hospitals in India. Sensitive parameters have yet to be found out. The study was conducted to find out whether diagnosis of myocarditis in clinically suspected cases can be done by measurement of serum levels of cardiac troponinI (cTnI and MB isoform of creatine kinase (CK-MB. MATERIALS AND METHODS 19 patients with clinically suspected myocarditis were screened for CK-MB activity and cTnI. Echocardiography, ECG and IgM for leptospirosis were also checked in these patients. RESULTS cTnI was elevated in 10 out of 19 patients with clinically suspected myocarditis. CK-MB was elevated in 7 patients. CONCLUSION Elevation of cTnI level in blood can be taken as an indicator of cardiac muscle cell injury in suspected cases of myocarditis.

[Cardiac safety of electroconvulsive therapy in an elderly patient--a case report].

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Karakuła-Juchnowicz, Hanna; Próchnicki, Michał; Kiciński, Paweł; Olajossy, Marcin; Pelczarska-Jamroga, Agnieszka; Dzikowski, Michał; Jaroszyński, Andrzej

2015-10-01

Since electroconvulsive therapy (ECT) was introduced as treatment for psychiatric disorders in 1938, it has remained one of the most effective therapeutic methods. ECT is often used as a "treatment of last resort" when other methods fail, and a life-saving procedure in acute clinical states when a rapid therapeutic effect is needed. Mortality associated with ECT is lower, compared to the treatment with tricyclic antidepressants, and comparable to that observed in so-called minor surgery. In the literature, cases of effective and safe electroconvulsive therapy have been described in patients of advanced age, with a burden of many somatic disorders. However, cases of acute cardiac episodes have also been reported during ECT. The qualification of patients for ECT and the selection of a group of patients at the highest risk of cardiovascular complications remains a serious clinical problem. An assessment of the predictive value of parameters of standard electrocardiogram (ECG), which is a simple, cheap and easily available procedure, deserves special attention. This paper reports a case of a 74-year-old male patient treated with ECT for a severe depressive episode, in the context of cardiologic safety. Both every single ECT session and the full course were assessed to examine their impact on levels of troponin T, which is a basic marker of cardiac damage, and selected ECG parameters (QTc, QRS). In the presented case ECT demonstrated its high general and cardiac safety with no negative effect on cardiac troponin (TnT) levels, corrected QT interval (QTc) duration, or other measured ECG parameters despite initially increased troponin levels, the patient's advanced age, the burden of a severe somatic disease and its treatment (anticancer therapy). © 2015 MEDPRESS.

Unusual towering elevation of troponin I after ST-elevation myocardial infarction and intensive monitoring with echocardiography post-percutaneous coronary intervention: a case report

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Suryadevara Ramya

2010-05-01

Full Text Available Abstract Introduction The elevation of troponin levels directly corresponds to the extent of myocardial injury. Here we present a case of a robust rise in cardiac biomarkers that correspond to extensive damage to the myocardium but did not spell doom for our patient. It is important to note that, to the best of our knowledge, this is the highest level of troponin I ever reported in the literature after a myocardial injury in an acute setting. Case presentation A 53-year-old African American man with an unknown medical history presented to the emergency room of our hospital with chest pain associated with diaphoresis and altered mental status. He required emergency intubation due to acute respiratory failure and circulatory collapse within 10 minutes of his arrival. He was started on heparin and eptifibatide (Integrilin drips but he was taken immediately for cardiac catheterization, which showed a total occlusion of his proximal left anterior descending, diffuse left circumflex disease and severe left ventricular dysfunction with segmental wall motion abnormality. He remained hypotensive throughout the procedure and an intra-aortic balloon pump was inserted for circulatory support. His urinary toxicology examination result was positive for cocaine metabolites. Serial echocardiograms showed an akinetic apex, a severely hypokinetic septum, and severe systolic dysfunction of his left ventricle. Our patient stayed at the Coronary Care Unit for a total of 15 days before he was finally discharged. Conclusion Studies demonstrate that an increase of 1 ng/ml in the cardiac troponin I level is associated with a significant increase in the risk ratio for death. The elevation of troponin I to 515 ng/ml in our patient is an unusual robust presentation which may reflect a composite of myocyte necrosis and reperfusion but without short-term mortality. Nevertheless, prolonged close monitoring is required for better outcome. We also emphasize the need for the

Cardiac Troponin T and Hydration Status as Prognostic Markers in Hemodialysis Patients.

Science.gov (United States)

Hoppe, Krzysztof; Schwermer, Krzysztof; Klysz, Patrycja; Radziszewska, Dorota; Sawatiuk, Peter; Baum, Ewa; Kaczmarek, Jolanta; Roszak, Magdalena; Kaluzna, Malgorzata; Lindholm, Bengt; Pawlaczyk, Krzysztof; Oko, Andrzej

2015-01-01

This study aimed to assess cardiac troponin T (cTnT) and hydration state as cardiovascular (CV) risk markers in hemodialysis (HD) patients. Two hundred and forty one patients were divided according to HD vintage into two groups: SV (HD ≤24 months) and LV. Water balance was assessed with overhydration (OH%; bioimpedance analysis) and daily diuresis (DD); CV dysfunction with cTnT and heart ultrasound; nutrition with subjective global assessment (SGA), cholesterol (TC) and albumin. SV had lower OH% (2.8 vs. 3.5, p < 0.05) and higher DD (1,161 vs. 637 ml, p < 0.001), while LV had higher cTnT (0.1 ± 0.04 vs. 0.1 ± 0.07 ng/ml, p < 0.05) and lower interventricular septum thickness (IVS; 13.4 vs. 14.5 mm, p < 0.05). Nutritional state as reflected by lower TC was worse in LV (184.7 vs. 169.5 mg/dl, p < 0.05). Mortality was higher in patients in the LV group (15 vs. 27 deaths, p < 0.05). OH% correlated inversely with albumin (r = -0.36, p < 0.001), TC (r = -0.31, p < 0.001) and cTnT (r = -0.4, p < 0.001). cTnT correlated positively with IVS (r = 0.39, p < 0.001), SGA (r = 0.23, p = 0.001) and mortality rate (r = 0.21, p < 0.01), and negatively with DD (r = -0.34, p < 0.001) and albumin (r = -0.25, p < 0.001). Longer dialysis vintage associates with CV dysfunction, overhydration and increased mortality, which may be predicted with OH% and cTnT. Video Journal Club ‘Cappuccino with Claudio Ronco' at http://www.karger.com/?doi=376603.

Influence of nitrous oxide anesthesia, B-vitamins, and MTHFR gene polymorphisms on perioperative cardiac events: the vitamins in nitrous oxide (VINO) randomized trial.

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Nagele, Peter; Brown, Frank; Francis, Amber; Scott, Mitchell G; Gage, Brian F; Miller, J Philip

2013-07-01

Nitrous oxide causes an acute increase in plasma homocysteine that is more pronounced in patients with the methylenetetrahydrofolate reductase (MTHFR) C677T or A1298C gene variant. In this randomized controlled trial, the authors sought to determine whether patients carrying the MTHFR C677T or A1298C variant had a higher risk for perioperative cardiac events after nitrous oxide anesthesia and whether this risk could be mitigated by B-vitamins. The authors randomized adult patients with cardiac risk factors undergoing noncardiac surgery, to receive nitrous oxide plus intravenous B-vitamins before and after surgery, or to nitrous oxide and placebo. Serial cardiac biomarkers and 12-lead electrocardiograms were obtained. The primary study endpoint was the incidence of myocardial injury, as defined by cardiac troponin I increase within the first 72 h after surgery. A total of 500 patients completed the trial. Patients who were homozygous for either MTHFR C677T, or A1298C gene variant (n=98; 19.6%) had no increased rate of postoperative cardiac troponin I increase compared with wild-type and heterozygous patients (11.2 vs. 14.0%; relative risk 0.96; 95% CI, 0.85-1.07; P=0.48). B-vitamins blunted the rise in homocysteine, but had no effect on cardiac troponin I increase compared with patients receiving placebo (13.2 vs. 13.6%; relative risk 1.02; 95% CI 0.78 to 1.32; P=0.91). Neither MTHFR C677T and A1298C gene variant, nor acute homocysteine increase are associated with perioperative cardiac troponin increase after nitrous oxide anesthesia. B-vitamins blunt nitrous oxide-induced homocysteine increase but have no effect on cardiac troponin I increase.

Influence of Nitrous Oxide Anesthesia, B-Vitamins, and MTHFR gene polymorphisms on Perioperative Cardiac Events: The Vitamins in Nitrous Oxide (VINO) Randomized Trial

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Nagele, Peter; Brown, Frank; Francis, Amber; Scott, Mitchell G.; Gage, Brian F.; Miller, J. Philip

2013-01-01

Background Nitrous oxide causes an acute increase in plasma homocysteine that is more pronounced in patients with the MTHFR C677T or A1298C gene variant. In this randomized controlled trial we sought to determine if patients carrying the MTHFR C677T or A1298C variant had a higher risk for perioperative cardiac events after nitrous oxide anesthesia and if this risk could be mitigated by B-vitamins. Methods We randomized adult patients with cardiac risk factors undergoing noncardiac surgery to receive nitrous oxide plus intravenous B-vitamins before and after surgery or to nitrous oxide and placebo. Serial cardiac biomarkers and 12-lead electrocardiograms were obtained. The primary study endpoint was the incidence of myocardial injury, as defined by cardiac troponin I elevation within the first 72 hours after surgery. Results A total of 500 patients completed the trial. Patients who were homozygous for either MTHFR C677T or A1298C gene variant (n= 98; 19.6%) had no increased rate of postoperative cardiac troponin I elevation compared to wild-type and heterozygous patients (11.2% vs. 14.0%; relative risk 0.96, 95% CI 0.85 to 1.07, p=0.48). B-vitamins blunted the rise in homocysteine, but had no effect on cardiac troponin I elevation compared to patients receiving placebo (13.2% vs. 13.6%; relative risk 1.02, 95% CI 0.78 to 1.32, p=0.91). Conclusions Neither MTHFR C677T and A1298C gene variant nor acute homocysteine increase are associated with perioperative cardiac troponin elevation after nitrousoxide anesthesia. B-vitamins blunt nitrous oxide-induced homocysteine increase but have no effect on cardiac troponin elevation. PMID:23856660

Operating characteristics of a qualitative troponin assay for the diagnosis of acute coronary syndrome.

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Farsi, Davood; Pishbin, Elham; Abbasi, Saeed; Hafezimoghadam, Peyman; Fathi, Marzieh; Zare, Mohammad Amin

2013-04-01

The troponin I serum level is widely used in acute coronary syndrome patients for their classification. The qualitative assay is faster and more available than the quantitative assay. The objective was to determine the operating characteristics of a qualitative troponin I assay compared with a quantitative method. This is a prospective observational study and patients suspected to have acute coronary syndrome were enrolled. A rapid troponin I test and a quantitative assay were carried out for each patient on arrival and 6 h after admission. A total of 262 patients were enrolled. The degree of agreement between the second rapid qualitative and quantitative troponin I was excellent (κ=0.946; 95% confidence interval, 0.903-0.989). The sensitivity, specificity, negative predictive value, and positive predictive value of the rapid qualitative troponin I test were 92.6, 100, 96.8, and 100%, respectively. In conclusion, this study reveals an excellent agreement between quantitative and qualitative bedside assays 6 h after admission in a sample of Iranian patients in the emergency department.

The impact of hepatitis B carrier on cardiac troponin I in 100-km ultramarathon runners.

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Li, Li-Hua; How, Chorng-Kuang; Kao, Wei-Fong; Chiu, Yu-Hui; Meng, Chen; Hsu, Cheng-Chin; Tsay, Yeou-Guang

2017-06-01

Prolonged endurance exercise is known to cause elevation of cardiac troponin I (cTnI). Previous studies have reported the correlation of several factors with exercise-induced cTnI release. However, the investigation of the predictors for elevated cTnI and postrace kinetics of cTnI after ultramarathon running is lacking, especially in an Oriental population. Twenty-six participants, including eight hepatitis B virus carrier (HBVc) runners, who finished a 100-km ultramarathon in Taiwan were enrolled. For each participant, blood samples were collected 1 week before the race, as well as immediately and 24 hours after the finish. The results showed that 19 runners (73.1%) had postrace elevated cTnI levels and eight (30.8%) had elevated cTnI values lasting more than 24 hours after the run. A multiple linear regression analysis demonstrated that the HBV status was a factor related to the high level of cTnI after 24 hours of running (β=0.03, p=0.08). The recovery of plasma cTnI levels was delayed in ultramarathon runners with latent HBV infection. Among HBVc runners, multiple linear regression analyses showed age (β=-0.01), previous running experience (β=-0.06), training distance (β=0.37), and 4 hours of running distance (β=-0.04) as significant predictors of higher postrace cTnI levels. For most athletes, cTnI values significantly increased immediately following the race in the absence of adverse clinical sequelae, and HBVc runners had higher and prolonged cTnI levels. While several factors are identified for such HBV effects, the specific causes need further elucidation. Copyright © 2017. Published by Elsevier Taiwan LLC.

The structure of the muscle protein complex 4Ca{sup 2+} {center_dot}troponin C {center_dot} troponin

Energy Technology Data Exchange (ETDEWEB)

Olah, G.A.; Trewhella, J. [Los Alamos National Laboratory, NM (United States)

1994-12-31

Analysis of scattering data based on a Monte Carlo integration method was used to 2+ obtain a low resolution model of the 4Ca{sup 2+}{circ} troponin C{circ}troponin I complex. This modeling method allows rapid testing of plausible structures where the best fit model can be ascertained by a comparison between model structure scattering profiles and measured scattering data. In the best fit model, troponin I appears as a spiral structure 2+ that wraps around 4Ca{sup 2+}{circ}troponin C which adopts an extended dumbbell conformation similar to that observed in the crystal structures of troponin C. The Monte Carlo modeling method can be applied to other biological systems in which detailed structural information is lacking.

A direct comparison of decision rules for early discharge of suspected acute coronary syndromes in the era of high sensitivity troponin.

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Chew, Pei Gee; Frost, Fredrick; Mullen, Liam; Fisher, Michael; Zadeh, Heidar; Grainger, Ruth; Albouaini, Khaled; Dodd, James; Patel, Bilal; Velavan, Periaswamy; Kunadian, Babu; Rawat, Anju; Obafemi, Toba; Tong, Sarah; Jones, Julia; Khand, Aleem

2018-02-01

We tested the hypothesis that a single high sensitivity troponin at limits of detection (LOD HSTnT) (Acute Coronary Events (GRACE) (acute coronary syndrome. In a prospective cohort study, risk scores were computed in consecutive patients with suspected acute coronary syndrome presenting to the Emergency Room of a large English hospital. Adjudication of myocardial infarction, as per third universal definition, involved a two-physician, blinded, independent review of all biomarker positive chest pain re-presentations to any national hospital. The primary and secondary outcome was a composite of type 1 myocardial infarction, unplanned coronary revascularisation and all cause death (MACE) at six weeks and one year. Of 3054 consecutive presentations with chest pain 1642 had suspected acute coronary syndrome (52% male, median age 59 years, 14% diabetic, 20% previous myocardial infarction). Median time from chest pain to presentation was 9.7 h. Re-presentations occurred in eight hospitals with 100% follow-up achieved. Two hundred and eleven (12.9%) and 279 (17%) were adjudicated to suffer MACE at six weeks and one year respectively. Only HEART ≤3 (negative predictive value MACE 99.4%, sensitivity 97.6%, %discharge 53.4) and LOD HSTnT strategy (negative predictive value MACE 99.8%, sensitivity 99.5%, %discharge 36.9) achieved pre-specified negative predictive value of >99% for MACE at six weeks. For type 1 myocardial infarction alone the negative predictive values at six weeks and one year were identical, for both HEART ≤3 and LOD HSTnT at 99.8% and 99.5% respectively. HEART ≤3 or LOD HSTnT strategy rules out short and medium term myocardial infarction with ≥99.5% certainty, and short-term MACE with >99% certainty, allowing for early discharge of 53.4% and 36.9% respectively of suspected acute coronary syndrome. Adoption of either strategy has the potential to greatly reduce Emergency Room pressures and minimise follow-up investigations. Very early presenters (<3 h

Molecular evaluation of five cardiac genes in Doberman Pinschers with dilated cardiomyopathy.

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Meurs, Kathryn M; Hendrix, Kristina P; Norgard, Michelle M

2008-08-01

To sequence the exonic and splice site regions of 5 cardiac genes associated with the human form of familial dilated cardiomyopathy (DCM) in Doberman Pinschers with DCM and to identify a causative mutation. 5 unrelated Doberman Pinschers with DCM and 2 unaffected Labrador Retrievers (control dogs). Exonic and splice site regions of the 5 genes encoding the cardiac proteins troponin C, lamin A/C, cysteine- and glycine-rich protein 3, cardiac troponin T, and the beta-myosin heavy chain were sequenced. Sequences were compared for nucleotide changes between affected dogs and the published canine sequences and 2 control dogs. Base pair changes were considered to be causative for DCM if they were present in an affected dog but not in the control dogs or published sequences and if they involved a conserved amino acid and changed that amino acid to a different polarity, acid-base status, or structure. A causative mutation for DCM in Doberman Pinschers was not identified, although single nucleotide polymorphisms were detected in some dogs in the cysteine- and glycine-rich protein 3, beta-myosin heavy chain, and troponin T genes. Mutations in 5 of the cardiac genes associated with the development of DCM in humans did not appear to be causative for DCM in Doberman Pinschers. Continued evaluation of additional candidate genes or a focused approach with an association analysis is warranted to elucidate the molecular cause of this important cardiac disease in Doberman Pinschers.

A universal system for highly efficient cardiac differentiation of human induced pluripotent stem cells that eliminates interline variability.

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Paul W Burridge

2011-04-01

Full Text Available The production of cardiomyocytes from human induced pluripotent stem cells (hiPSC holds great promise for patient-specific cardiotoxicity drug testing, disease modeling, and cardiac regeneration. However, existing protocols for the differentiation of hiPSC to the cardiac lineage are inefficient and highly variable. We describe a highly efficient system for differentiation of human embryonic stem cells (hESC and hiPSC to the cardiac lineage. This system eliminated the variability in cardiac differentiation capacity of a variety of human pluripotent stem cells (hPSC, including hiPSC generated from CD34(+ cord blood using non-viral, non-integrating methods.We systematically and rigorously optimized >45 experimental variables to develop a universal cardiac differentiation system that produced contracting human embryoid bodies (hEB with an improved efficiency of 94.7±2.4% in an accelerated nine days from four hESC and seven hiPSC lines tested, including hiPSC derived from neonatal CD34(+ cord blood and adult fibroblasts using non-integrating episomal plasmids. This cost-effective differentiation method employed forced aggregation hEB formation in a chemically defined medium, along with staged exposure to physiological (5% oxygen, and optimized concentrations of mesodermal morphogens BMP4 and FGF2, polyvinyl alcohol, serum, and insulin. The contracting hEB derived using these methods were composed of high percentages (64-89% of cardiac troponin I(+ cells that displayed ultrastructural properties of functional cardiomyocytes and uniform electrophysiological profiles responsive to cardioactive drugs.This efficient and cost-effective universal system for cardiac differentiation of hiPSC allows a potentially unlimited production of functional cardiomyocytes suitable for application to hPSC-based drug development, cardiac disease modeling, and the future generation of clinically-safe nonviral human cardiac cells for regenerative medicine.

Cardiac damage associated with stress hyperglycaemia and acute coronary syndrome changes according to level of presenting blood glucose.

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Al Jumaily, Talib; Rose'Meyer, Roselyn B; Sweeny, Amy; Jayasinghe, Rohan

2015-10-01

To determine the prevalence of stress hyperglycaemia in people presenting with acute coronary syndrome (ACS), and the relationships between admission glucose and cardiac damage, cardiovascular mortality and morbidity. In a prospective observational study people presenting with ACS at the Gold Coast Hospital had their admission glucose (AG) level tested to determine stress hyperglycaemia. A range of measurements supplemented this data including troponin levels, category of ACS and major adverse coronary events (MACEs) were obtained through hospital records and patient follow-up post-discharge. One hundred eighty-eight participants were recruited. The prevalence of stress hyperglycaemia in ACS was 44% with 31% having a previous diagnosis of type 2 diabetes and 7.7% had undiagnosed diabetes. The stress hyperglycaemic group had a significantly higher median troponin levels compared to participants with normal blood glucose levels on admission (pglucose group (>15 mmol/L) had troponin levels similar to people presenting with normal blood glucose levels and ACS (p>0.05). Cardiac necrosis as measured by troponin levels is significantly increased in people with ACS and stress hyperglycaemia. This study found that one in four participants presenting with ACS and an admission glucose of >7.0 had no previous diagnosis for diabetes. Consistently ordering HbA1C testing on patients with high AG can enable earlier diagnosis and treatment of diabetes. Copyright © 2015. Published by Elsevier Ireland Ltd.

Troponin T elevation after permanent pacemaker implantation.

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Chen, Xueying; Yu, Ziqing; Bai, Jin; Hu, Shulan; Wang, Wei; Qin, Shengmei; Wang, Jingfeng; Sun, Zhe; Su, Yangang; Ge, Junbo

2017-08-01

The objective of the study is to study the incidence, significance, and factors associated with cardiac troponin T (CTNT) elevation after pacemaker implantation. Three hundred seventy-four patients (104 single-chamber pacemakers or ICD, 243 dual-chamber pacemakers, and 27 cardiac resynchronization therapy/cardiac resynchronization therapy defibrillator) who had normal levels of CTNT at baseline and underwent implantation of a permanent pacemaker system were included in this study. Serum levels of CTNT were measured at baseline, 6 and 24 h after the implantation procedure. The median of CTNT levels increased from 0.012 ng/mL at baseline to 0.032 and 0.019 ng/mL at 6 and 24 h after the procedure, respectively (all p 0.09 ng/mL). After 1-year follow-up, the incidence of complications including dislodgement of the lead, pocket infection, pneumothorax, hemothorax, and vein thrombus and cardiac outcomes including hospitalization of heart failure, coronary artery disease, arrhythmia, and cardiovascular mortality was not significantly different between the normal and elevated CTNT groups at 6 h after the procedure. By logistic regression analysis, gender, N-terminal pro-B type natriuretic peptide (NT-pro-BNP) at baseline, left ventricular ejection fractions (LVEF), estimated glomerular filtration rate (eGFR), and fluoroscopy time were independently associated with CTNT elevation after adjusted for age, pacemaker types, right ventricle lead location (RVA or RVOT), heart function, and left ventricular end systolic dimension. Pacemaker implantation was found to be accompanied with CTNT elevation in 55.6% of the patients at 6 h after the procedure, and its kinetics were fast, which might not be related to the complications and adverse cardiac outcomes within 1 year of follow-up. Moreover, gender, NT-pro-BNP at baseline, LVEF, eGFR, and fluoroscopy time were found to be independent predictors of CTNT elevation.

Cardiac effects of positive pressure ventilation in ARDS assessed by NT-proBNP, Troponin T and Troponin I

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Yasser Sadek Nassar

2013-01-01

Although the increase in cardiac markers are insignificant, yet they point to the potentially harmful role played by high PEEP, low PH and low PaO2/FiO2 ratio on the heart. Currently, no clinically relevant conclusion can be drawn apart from the recommendation to attempt to lower PEEP and shorten the duration of positive pressure ventilation, even in patients with structurally normal hearts.

3-OST-7 regulates BMP-dependent cardiac contraction.

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Shiela C Samson

2013-12-01

Full Text Available The 3-O-sulfotransferase (3-OST family catalyzes rare modifications of glycosaminoglycan chains on heparan sulfate proteoglycans, yet their biological functions are largely unknown. Knockdown of 3-OST-7 in zebrafish uncouples cardiac ventricular contraction from normal calcium cycling and electrophysiology by reducing tropomyosin4 (tpm4 expression. Normal 3-OST-7 activity prevents the expansion of BMP signaling into ventricular myocytes, and ectopic activation of BMP mimics the ventricular noncontraction phenotype seen in 3-OST-7 depleted embryos. In 3-OST-7 morphants, ventricular contraction can be rescued by overexpression of tropomyosin tpm4 but not by troponin tnnt2, indicating that tpm4 serves as a lynchpin for ventricular sarcomere organization downstream of 3-OST-7. Contraction can be rescued by expression of 3-OST-7 in endocardium, or by genetic loss of bmp4. Strikingly, BMP misregulation seen in 3-OST-7 morphants also occurs in multiple cardiac noncontraction models, including potassium voltage-gated channel gene, kcnh2, affected in Romano-Ward syndrome and long-QT syndrome, and cardiac troponin T gene, tnnt2, affected in human cardiomyopathies. Together these results reveal 3-OST-7 as a key component of a novel pathway that constrains BMP signaling from ventricular myocytes, coordinates sarcomere assembly, and promotes cardiac contractile function.

Milrinone and esmolol decrease cardiac damage after resuscitation from prolonged cardiac arrest.

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Zoerner, F; Lennmyr, F; Wiklund, L; Martijn, C; Semenas, E

2015-04-01

Long-term survival after cardiac arrest (CA) due to shock-refractory ventricular fibrillation (VF) is low. Clearly, there is a need for new pharmacological interventions in the setting of cardiopulmonary resuscitation (CPR) to improve outcome. Here, hemodynamic parameters and cardiac damage are compared between the treatment group (milrinone, esmolol and vasopressin) and controls (vasopressin only) during resuscitation from prolonged CA in piglets. A total of 26 immature male piglets were subjected to 12-min VF followed by 8-min CPR. The treatment group (n=13) received i.v. (intravenous) boluses vasopressin 0.4 U/kg, esmolol 250 μg/kg and milrinone 25 μg/kg after 13 min, followed by i.v. boluses esmolol 375 μg/kg and milrinone 25 μg/kg after 18 min and continuous esmolol 15 μg/kg/h infusion during 180 min reperfusion, whereas controls (n=13) received equal amounts of vasopressin and saline. A 200 J monophasic counter-shock was delivered to achieve resumption of spontaneous circulation (ROSC) after 8 min CPR. If ROSC was not achieved, another 200 J defibrillation and bolus vasopressin 0.4 U/kg would be administered in both groups. Direct current shocks at 360 J were applied as one shot per minute over maximally 5 min. Hemodynamic variables and troponin I as a marker of cardiac injury were recorded. Troponin I levels after 180 min reperfusion were lower in the treatment group than in controls (Pmilrinone, esmolol and vasopressin decreased cardiac injury compared with vasopressin alone. © 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Cardiovascular biomarkers and sex: the case for women.

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Daniels, Lori B; Maisel, Alan S

2015-10-01

Measurement of biomarkers is a critical component of cardiovascular care. Women and men differ in their cardiac physiology and manifestations of cardiovascular disease. Although most cardiovascular biomarkers are used by clinicians without taking sex into account, sex-specific differences in biomarkers clearly exist. Baseline concentrations of many biomarkers (including cardiac troponin, natriuretic peptides, galectin-3, and soluble ST2) differ in men versus women, but these sex-specific differences do not generally translate into a need for differential sex-based cut-off points. Furthermore, most biomarkers are similarly diagnostic and prognostic, regardless of sex. Two potential exceptions are cardiac troponins measured by high-sensitivity assay, and proneurotensin. Troponin levels are lower in women than in men and, with the use of high-sensitivity assays, sex-specific cut-off points might improve the diagnosis of myocardial infarction. Proneurotensin is a novel biomarker that was found to be predictive of incident cardiovascular disease in women, but not men, and was also predictive of incident breast cancer. If confirmed, proneurotensin might be a unique biomarker of disease risk in women. With any biomarker, an understanding of sex-specific differences might improve its use and might also lead to an enhanced understanding of the physiological differences between the hearts of men and women.

Evaluation of C-reactive protein, Haptoglobin and cardiac troponin 1 levels in brachycephalic dogs with upper airway obstructive syndrome

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Planellas Marta

2012-08-01

Full Text Available Abstract Background Brachycephalic dogs have unique upper respiratory anatomy with abnormal breathing patterns similar to those in humans with obstructive sleep apnea syndrome (OSAS. The objective of this study was to evaluate the correlation between anatomical components, clinical signs and several biomarkers, used to determine systemic inflammation and myocardial damage (C-reactive protein, CRP; Haptoglobin, Hp; cardiac troponin I, cTnI, in dogs with brachycephalic upper airway obstructive syndrome (BAOS. Results Fifty brachycephalic dogs were included in the study and the following information was studied: signalment, clinical signs, thoracic radiographs, blood work, ECG, components of BAOS, and CRP, Hp and cTnI levels. A high proportion of dogs with BAOS (88% had gastrointestinal signs. The prevalence of anatomic components of BAOS was: elongated soft palate (100%, stenotic nares (96%, everted laryngeal saccules (32% and tracheal hypoplasia (29.1%. Increased serum levels of biomarkers were found in a variable proportion of dogs: 14% (7/50 had values of CRP > 20 mg/L, 22.9% (11/48 had values of Hp > 3 g/L and 47.8% (22/46 had levels of cTnI > 0.05 ng/dl. Dogs with everted laryngeal saccules had more severe respiratory signs (p Conclusions According to the low percentage of patients with elevated levels of CRP and Hp, BAOS does not seem to cause an evident systemic inflammatory status. Some degree of myocardial damage may occur in dogs with BAOS that can be detected by cTnI concentration.

Obstructive sleep apnea: no independent association to troponins.

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Hall, Trygve Sørdahl; Herrscher, Tobias; Jarolim, Petr; Fagerland, Morten W; Jensen, Torstein; Hallén, Jonas; Agewall, Stefan; Atar, Dan

2014-05-01

Cardiac troponins (cTn) are to date the most sensitive and specific biochemical markers of myocardial injury. Abnormal breathing patterns in patients with obstructive sleep apnea (OSA) may cause myocardial cell stress detectable by novel cTn assays. The objectives of this study were to investigate whether a new single-molecule cTnI (S-cTnI) assay and a commercially available high-sensitivity cTnT (hs-cTnT) assay would detect myocyte injury in individuals evaluated for possible OSA, and to explore their relation to variables of disordered breathing during sleep. Consecutive individuals referred to Lovisenberg Diakonale Hospital's sleep laboratory between 1 October 2009 and 1 March 2010 were included. We measured cTn in specimens collected the morning after sleep and studied these in relation to variables recorded during polygraphy or polysomnography. All 222 (100 %) individuals had measurable cTn levels using either assay. Stratified into categories according to the apnea-hypopnea index (AHI), patients with OSA (AHI ≥5) had a different distribution of S-cTnI (P = 0.036) and hs-cTnT (P = 0.002) compared to those without (AHI <5). The median (quartiles 1-3) were 3.0 (1.9-6.0) versus 2.3 (1.6-3.8) ng/l for S-cTnI, and 7.0 (5.5-8.7) versus 6.2 (4.9-7.2) ng/l for hs-cTnT. However, in multiple median regression analyses adjusted for conventional predictors, neither S-cTnI (P = 0.57) nor hs-cTnT (P = 0.80) were significantly associated with AHI. This study reveals no association independent of conventional predictors between OSA and myocardial cell injury measured by S-cTnI and hs-cTnT assays. Our findings support a search for novel biomarkers for prognostication of OSA.

Troponin T is a strong marker of mortality in hospitalized patients

DEFF Research Database (Denmark)

Iversen, Kasper; Køber, Lars; Gøtze, Jens Peter

2013-01-01

hospitalized population are unknown. METHODS: Consecutive patients aged >40years admitted to a district hospital between 1 April 1998 and 31 March 1999 were included. A comprehensive medical interview and clinical examination were performed including echocardiography and measurement of natriuretic peptides...... and troponin T with a high-sensitivity assay (hs-TnT). RESULTS: Serum for analyses of hs-TnT was available from 1176 patients. Patients were 73.7years old on average (interquartile range, 64.5-80.0years), 59.2% were women and median follow-up was 11.4years. The prevalence of elevated hs-TnT (> 99th percentile...

Prognostic value of predischarge dobutamine stress echocardiography in chest pain patients with a negative cardiac troponin T

NARCIS (Netherlands)

Bholasingh, Radha; Cornel, Jan Hein; Kamp, Otto; van Straalen, Jan P.; Sanders, Gerard T.; Tijssen, Jan G. P.; Umans, Victor A. W. M.; Visser, Cees A.; de Winter, Robbert J.

2003-01-01

OBJECTIVES We prospectively studied the prognostic value of predischarge dobutamine stress echocardiography (I)SE) in low-risk chest pain patients with a normal or nondiagnostic electrocardiogram (ECG) and a negative serial troponin T. BACKGROUND Noninvasive stress testing is recommended before

Hypertrophic cardiomyopathy-linked mutation in troponin T causes myofibrillar disarray and pro-arrhythmic action potential changes in human iPSC cardiomyocytes.

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Wang, Lili; Kim, Kyungsoo; Parikh, Shan; Cadar, Adrian Gabriel; Bersell, Kevin R; He, Huan; Pinto, Jose R; Kryshtal, Dmytro O; Knollmann, Bjorn C

2018-01-01

Mutations in cardiac troponin T (TnT) are linked to increased risk of ventricular arrhythmia and sudden death despite causing little to no cardiac hypertrophy. Studies in mice suggest that the hypertrophic cardiomyopathy (HCM)-associated TnT-I79N mutation increases myofilament Ca sensitivity and is arrhythmogenic, but whether findings from mice translate to human cardiomyocyte electrophysiology is not known. To study the effects of the TnT-I79N mutation in human cardiomyocytes. Using CRISPR/Cas9, the TnT-I79N mutation was introduced into human induced pluripotent stem cells (hiPSCs). We then used the matrigel mattress method to generate single rod-shaped cardiomyocytes (CMs) and studied contractility, Ca handling and electrophysiology. Compared to isogenic control hiPSC-CMs, TnT-I79N hiPSC-CMs exhibited sarcomere disorganization, increased systolic function and impaired relaxation. The Ca-dependence of contractility was leftward shifted in mutation containing cardiomyocytes, demonstrating increased myofilament Ca sensitivity. In voltage-clamped hiPSC-CMs, TnT-I79N reduced intracellular Ca transients by enhancing cytosolic Ca buffering. These changes in Ca handling resulted in beat-to-beat instability and triangulation of the cardiac action potential, which are predictors of arrhythmia risk. The myofilament Ca sensitizer EMD57033 produced similar action potential triangulation in control hiPSC-CMs. The TnT-I79N hiPSC-CM model not only reproduces key cellular features of TnT-linked HCM such as myofilament disarray, hypercontractility and diastolic dysfunction, but also suggests that this TnT mutation causes pro-arrhythmic changes of the human ventricular action potential. Copyright © 2017 Elsevier Ltd. All rights reserved.

Interoception across modalities: on the relationship between cardiac awareness and the sensitivity for gastric functions.

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Beate M Herbert

Full Text Available The individual sensitivity for ones internal bodily signals ("interoceptive awareness" has been shown to be of relevance for a broad range of cognitive and affective functions. Interoceptive awareness has been primarily assessed via measuring the sensitivity for ones cardiac signals ("cardiac awareness" which can be non-invasively measured by heartbeat perception tasks. It is an open question whether cardiac awareness is related to the sensitivity for other bodily, visceral functions. This study investigated the relationship between cardiac awareness and the sensitivity for gastric functions in healthy female persons by using non-invasive methods. Heartbeat perception as a measure for cardiac awareness was assessed by a heartbeat tracking task and gastric sensitivity was assessed by a water load test. Gastric myoelectrical activity was measured by electrogastrography (EGG and subjective feelings of fullness, valence, arousal and nausea were assessed. The results show that cardiac awareness was inversely correlated with ingested water volume and with normogastric activity after water load. However, persons with good and poor cardiac awareness did not differ in their subjective ratings of fullness, nausea and affective feelings after drinking. This suggests that good heartbeat perceivers ingested less water because they subjectively felt more intense signals of fullness during this lower amount of water intake compared to poor heartbeat perceivers who ingested more water until feeling the same signs of fullness. These findings demonstrate that cardiac awareness is related to greater sensitivity for gastric functions, suggesting that there is a general sensitivity for interoceptive processes across the gastric and cardiac modality.

Troponin T3 expression in skeletal and smooth muscle is required for growth and postnatal survival: characterization of Tnnt3(tm2a(KOMP)Wtsi) mice.

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Ju, Yawen; Li, Jie; Xie, Chao; Ritchlin, Christopher T; Xing, Lianping; Hilton, Matthew J; Schwarz, Edward M

2013-09-01

The troponin complex, which consists of three regulatory proteins (troponin C, troponin I, and troponin T), is known to regulate muscle contraction in skeletal and cardiac muscle, but its role in smooth muscle remains controversial. Troponin T3 (TnnT3) is a fast skeletal muscle troponin believed to be expressed only in skeletal muscle cells. To determine the in vivo function and tissue-specific expression of Tnnt3, we obtained the heterozygous Tnnt3+/flox/lacZ mice from Knockout Mouse Project (KOMP) Repository. Tnnt3(lacZ/+) mice are smaller than their WT littermates throughout development but do not display any gross phenotypes. Tnnt3(lacZ/lacZ) embryos are smaller than heterozygotes and die shortly after birth. Histology revealed hemorrhagic tissue in Tnnt3(lacZ/lacZ) liver and kidney, which was not present in Tnnt3(lacZ/+) or WT, but no other gross tissue abnormalities. X-gal staining for Tnnt3 promoter-driven lacZ transgene expression revealed positive staining in skeletal muscle and diaphragm and smooth muscle cells located in the aorta, bladder, and bronchus. Collectively, these findings suggest that troponins are expressed in smooth muscle and are required for normal growth and breathing for postnatal survival. Moreover, future studies with this mouse model can explore TnnT3 function in adult muscle function using the conditional-inducible gene deletion approach Copyright © 2013 Wiley Periodicals, Inc.

Genotype‐specific pathogenic effects in human dilated cardiomyopathy

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Schuldt, Maike; Harakalova, Magdalena; Vink, Aryan; Asselbergs, Folkert W.; Pinto, Jose R.; Krüger, Martina; Kuster, Diederik W. D.; van der Velden, Jolanda

2017-01-01

Key points Mutations in genes encoding cardiac troponin I (TNNI3) and cardiac troponin T (TNNT2) caused altered troponin protein stoichiometry in patients with dilated cardiomyopathy. TNNI3p.98trunc resulted in haploinsufficiency, increased Ca2+‐sensitivity and reduced length‐dependent activation. TNNT2p.K217del caused increased passive tension.A mutation in the gene encoding Lamin A/C (LMNA p.R331Q) led to reduced maximal force development through secondary disease remodelling in patients suffering from dilated cardiomyopathy.Our study shows that different gene mutations induce dilated cardiomyopathy via diverse cellular pathways. Abstract Dilated cardiomyopathy (DCM) can be caused by mutations in sarcomeric and non‐sarcomeric genes. In this study we defined the pathogenic effects of three DCM‐causing mutations: the sarcomeric mutations in genes encoding cardiac troponin I (TNNI3p.98truncation) and cardiac troponin T (TNNT2p.K217deletion; also known as the p.K210del) and the non‐sarcomeric gene mutation encoding lamin A/C (LMNAp.R331Q). We assessed sarcomeric protein expression and phosphorylation and contractile behaviour in single membrane‐permeabilized cardiomyocytes in human left ventricular heart tissue. Exchange with recombinant troponin complex was used to establish the direct pathogenic effects of the mutations in TNNI3 and TNNT2. The TNNI3p.98trunc and TNNT2p.K217del mutation showed reduced expression of troponin I to 39% and 51%, troponin T to 64% and 53%, and troponin C to 73% and 97% of controls, respectively, and altered stoichiometry between the three cardiac troponin subunits. The TNNI3p.98trunc showed pure haploinsufficiency, increased Ca2+‐sensitivity and impaired length‐dependent activation. The TNNT2p.K217del mutation showed a significant increase in passive tension that was not due to changes in titin isoform composition or phosphorylation. Exchange with wild‐type troponin complex corrected troponin protein levels to 83% of

Salt-Sensitive Hypertension and Cardiac Hypertrophy in Transgenic Mice Expressing a Corin Variant Identified in African Americans

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Wang, Wei; Cui, Yujie; Shen, Jianzhong; Jiang, Jingjing; Chen, Shenghan; Peng, Jianhao; Wu, Qingyu

2012-01-01

African Americans represent a high risk population for salt-sensitive hypertension and heart disease but the underlying mechanism remains unclear. Corin is a cardiac protease that regulates blood pressure by activating natriuretic peptides. A corin gene variant (T555I/Q568P) was identified in African Americans with hypertension and cardiac hypertrophy. In this study, we test the hypothesis that the corin variant contributes to the hypertensive and cardiac hypertrophic phenotype in vivo. Transgenic mice were generated to express wild-type or T555I/Q568P variant corin in the heart under the control of α-myosin heavy chain promoter. The mice were crossed into a corin knockout background to create KO/TgWT and KO/TgV mice that expressed WT or variant corin, respectively, in the heart. Functional studies showed that KO/TgV mice had significantly higher levels of pro-atrial natriuretic peptide in the heart compared with that in control KO/TgWT mice, indicating that the corin variant was defective in processing natriuretic peptides in vivo. By radiotelemetry, corin KO/TgV mice were found to have hypertension that was sensitive to dietary salt loading. The mice also developed cardiac hypertrophy at 12–14 months of age when fed a normal salt diet or at a younger age when fed a high salt diet. The phenotype of salt-sensitive hypertension and cardiac hypertrophy in KO/TgV mice closely resembles the pathological findings in African Americans who carry the corin variant. The results indicate that corin defects may represent an important mechanism in salt-sensitive hypertension and cardiac hypertrophy in African Americans. PMID:22987923

Coronary collateral circulation in patients with chronic coronary total occlusion; its relationship with cardiac risk markers and SYNTAX score.

Science.gov (United States)

Börekçi, A; Gür, M; Şeker, T; Baykan, A O; Özaltun, B; Karakoyun, S; Karakurt, A; Türkoğlu, C; Makça, I; Çaylı, M

2015-09-01

Compared to patients without a collateral supply, long-term cardiac mortality is reduced in patients with well-developed coronary collateral circulation (CCC). Cardiovascular risk markers, such as N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitive C-reactive protein (hs-CRP) and high-sensitive cardiac troponin T (hs-cTnT) are independent predictors for cardiovascular mortality. The main goal of this study was to examine the relationship between CCC and cardiovascular risk markers. We prospectively enrolled 427 stable coronary artery disease patients with chronic total occlusion (mean age: 57.5±11.1 years). The patients were divided into two groups, according to their Rentrop scores: (a) poorly developed CCC group (Rentrop 0 and 1) and (b) well-developed CCC group (Rentrop 2 and 3). NT-proBNP, hs-CRP, hs-cTnT, uric acid and other biochemical markers were also measured. The SYNTAX score was calculated for all patients. The patients in the poorly developed CCC group had higher frequencies of diabetes and hypertension (prisk markers, such as NT-proBNP, hs-cTnT and hs-CRP are independently associated with CCC in stable coronary artery disease with chronic total occlusion. © The Author(s) 2014.

Troponins Test

Science.gov (United States)

... lab's website in order to provide you with background information about the test(s) you had performed. You will need to return ... C, Banfi G, Guidi GC. Influence of a half-marathon run on NT-proBNP and troponin ... MedlinePlus Medical Encyclopedia [On-line information]. Available online ...

S-glutathionylation of troponin I (fast) increases contractile apparatus Ca2+ sensitivity in fast-twitch muscle fibres of rats and humans.

Science.gov (United States)

Mollica, J P; Dutka, T L; Merry, T L; Lamboley, C R; McConell, G K; McKenna, M J; Murphy, R M; Lamb, G D

2012-03-15

Oxidation can decrease or increase the Ca2+ sensitivity of the contractile apparatus in rodent fast-twitch (type II) skeletal muscle fibres, but the reactions and molecular targets involved are unknown. This study examined whether increased Ca2+ sensitivity is due to S-glutathionylation of particular cysteine residues. Skinned muscle fibres were directly activated in heavily buffered Ca2+ solutions to assess contractile apparatus Ca2+ sensitivity. Rat type II fibres were subjected to S-glutathionylation by successive treatments with 2,2′-dithiodipyridine (DTDP) and glutathione (GSH), and displayed a maximal increase in pCa50 (−log10 [Ca2+] at half-maximal force) of ∼0.24 pCa units, with little or no effect on maximum force or Hill coefficient. Partial similar effect was produced by exposure to oxidized gluthathione (GSSG, 10 mM) for 10 min at pH 7.1, and near-maximal effect by GSSG treatment at pH 8.5. None of these treatments significantly altered Ca2+ sensitivity in rat type I fibres. Western blotting showed that both the DTDP–GSH and GSSG–pH 8.5 treatments caused marked S-glutathionylation of the fast troponin I isoform (TnI(f)) present in type II fibres, but not of troponin C (TnC) or myosin light chain 2. Both the increased Ca2+ sensitivity and glutathionylation of TnI(f) were blocked by N-ethylmaleimide (NEM). S-nitrosoglutathione (GSNO) also increased Ca2+ sensitivity, but only in conditions where it caused S-glutathionylation of TnI(f). In human type II fibres from vastus lateralis muscle, DTDP–GSH treatment also caused similar increased Ca2+ sensitivity and S-glutathionylation of TnI(f). When the slow isoform of TnI in type I fibres of rat was partially substituted (∼30%) with TnI(f), DTDP–GSH treatment caused a significant increase in Ca2+ sensitivity (∼0.08 pCa units). TnIf in type II fibres from toad and chicken muscle lack Cys133 present in mammalian TnIf, and such fibres showed no change in Ca2+ sensitivity with DTDP–GSH nor any S

Circulating Histones Are Major Mediators of Cardiac Injury in Patients With Sepsis.

Science.gov (United States)

Alhamdi, Yasir; Abrams, Simon T; Cheng, Zhenxing; Jing, Shengjie; Su, Dunhao; Liu, Zhiyong; Lane, Steven; Welters, Ingeborg; Wang, Guozheng; Toh, Cheng-Hock

2015-10-01

To investigate the impact of circulating histones on cardiac injury and dysfunction in a murine model and patients with sepsis. Prospective, observational clinical study with in vivo and ex vivo translational laboratory investigations. General ICU and university research laboratory. Sixty-five septic patients and 27 healthy volunteers. Twelve-week-old male C57BL/6N mice. Serial blood samples from 65 patients with sepsis were analyzed, and left ventricular function was assessed by echocardiography. Patients' sera were incubated with cultured cardiomyocytes in the presence or absence of antihistone antibody, and cellular viability was assessed. Murine sepsis was initiated by intraperitoneal Escherichia coli injection (10(8) colony-forming unit/mouse) in 12-week-old male C57BL/6N mice, and the effect of antihistone antibody (10 mg/kg) was studied. Murine blood samples were collected serially, and left ventricular function was assessed by intraventricular catheters and electrocardiography. Circulating histones and cardiac troponins in human and murine plasma were quantified. In 65 patients with sepsis, circulating histones were significantly elevated compared with healthy controls (n = 27) and linearly correlated with cardiac troponin T levels (rs = 0.650; p histone levels were significantly associated with new-onset left ventricular dysfunction (p = 0.001) and arrhythmias (p = 0.01). Left ventricular dysfunction only predicted adverse outcomes when combined with elevated histones or cardiac troponin levels. Furthermore, patients' sera directly induced histone-specific cardiomyocyte death ex vivo, which was abrogated by antihistone antibodies. In vivo studies on septic mice confirmed the cause-effect relationship between circulating histones and the development of cardiac injury, arrhythmias, and left ventricular dysfunction. Circulating histones are novel and important mediators of septic cardiomyopathy, which can potentially be utilized for prognostic and therapeutic

High fat diet-fed obese rats are highly sensitive to doxorubicin-induced cardiotoxicity

International Nuclear Information System (INIS)

Mitra, Mayurranjan S.; Donthamsetty, Shashikiran; White, Brent; Mehendale, Harihara M.

2008-01-01

Often, chemotherapy by doxorubicin (Adriamycin) is limited due to life threatening cardiotoxicity in patients during and posttherapy. Recently, we have shown that moderate diet restriction remarkably protects against doxorubicin-induced cardiotoxicity. This cardioprotection is accompanied by decreased cardiac oxidative stress and triglycerides and increased cardiac fatty-acid oxidation, ATP synthesis, and upregulated JAK/STAT3 pathway. In the current study, we investigated whether a physiological intervention by feeding 40% high fat diet (HFD), which induces obesity in male Sprague-Dawley rats (250-275 g), sensitizes to doxorubicin-induced cardiotoxicity. A LD 10 dose (8 mg doxorubicin/kg, ip) administered on day 43 of the HFD feeding regimen led to higher cardiotoxicity, cardiac dysfunction, lipid peroxidation, and 80% mortality in the obese (OB) rats in the absence of any significant renal or hepatic toxicity. Doxorubicin toxicokinetics studies revealed no change in accumulation of doxorubicin and doxorubicinol (toxic metabolite) in the normal diet-fed (ND) and OB hearts. Mechanistic studies revealed that OB rats are sensitized due to: (1) higher oxyradical stress leading to upregulation of uncoupling proteins 2 and 3, (2) downregulation of cardiac peroxisome proliferators activated receptor-α, (3) decreased plasma adiponectin levels, (4) decreased cardiac fatty-acid oxidation (666.9 ± 14.0 nmol/min/g heart in ND versus 400.2 ± 11.8 nmol/min/g heart in OB), (5) decreased mitochondrial AMP-α2 protein kinase, and (6) 86% drop in cardiac ATP levels accompanied by decreased ATP/ADP ratio after doxorubicin administration. Decreased cardiac erythropoietin and increased SOCS3 further downregulated the cardioprotective JAK/STAT3 pathway. In conclusion, HFD-induced obese rats are highly sensitized to doxorubicin-induced cardiotoxicity by substantially downregulating cardiac mitochondrial ATP generation, increasing oxidative stress and downregulating the JAK/STAT3

Therapy with mesenchymal stromal cells or conditioned medium reverse cardiac alterations in a high-fat diet-induced obesity model.

Science.gov (United States)

Daltro, P S; Barreto, B C; Silva, P G; Neto, P Chenaud; Sousa Filho, P H F; Santana Neta, D; Carvalho, G B; Silva, D N; Paredes, B D; de Alcantara, A C; Freitas, L A R; Couto, R D; Santos, R R; Souza, B S F; Soares, M B P; Macambira, S G

2017-10-01

Obesity is associated with numerous cardiac complications, including arrhythmias, cardiac fibrosis, remodeling and heart failure. Here we evaluated the therapeutic potential of mesenchymal stromal cells (MSCs) and their conditioned medium (CM) to treat cardiac complications in a mouse model of high-fat diet (HFD)-induced obesity. After obesity induction and HFD withdrawal, obese mice were treated with MSCs, CM or vehicle. Cardiac function was assessed using electrocardiography, echocardiography and treadmill test. Body weight and biochemical parameters were evaluated. Cardiac tissue was used for real time (RT)-polymerase chain reaction (PCR) and histopathologic analysis. Characterization of CM by protein array showed the presence of different cytokines and growth factors, including chemokines, osteopontin, cystatin C, Serpin E1 and Gas 6. HFD-fed mice presented cardiac arrhythmias, altered cardiac gene expression and fibrosis reflected in physical exercise incapacity associated with obesity and diabetes. Administration of MSCs or CM improved arrhythmias and exercise capacity. This functional improvement correlated with normalization of GATA4 gene expression in the hearts of MSC- or CM-treated mice. The gene expression of connexin 43, troponin I, adiponectin, transforming growth factor (TGF) β, peroxisome proliferator activated receptor gamma (PPARγ), insulin-like growth factor 1 (IGF-1), matrix metalloproteinase-9 (MMP9) and tissue inhibitor of metalloproteinases 1 (TIMP1) were significantly reduced in MSCs, but not in CM-treated mice. Moreover, MSC or CM administration reduced the intensity of cardiac fibrosis. Our results suggest that MSCs and CM have a recovery effect on cardiac disturbances due to obesity and corroborate to the paracrine action of MSCs in heart disease models. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

A Metabolite-Sensitive, Thermodynamically Constrained Model of Cardiac Cross-Bridge Cycling: Implications for Force Development during Ischemia

KAUST Repository

Tran, Kenneth; Smith, Nicolas P.; Loiselle, Denis S.; Crampin, Edmund J.

2010-01-01

We present a metabolically regulated model of cardiac active force generation with which we investigate the effects of ischemia on maximum force production. Our model, based on a model of cross-bridge kinetics that was developed by others, reproduces many of the observed effects of MgATP, MgADP, Pi, and H(+) on force development while retaining the force/length/Ca(2+) properties of the original model. We introduce three new parameters to account for the competitive binding of H(+) to the Ca(2+) binding site on troponin C and the binding of MgADP within the cross-bridge cycle. These parameters, along with the Pi and H(+) regulatory steps within the cross-bridge cycle, were constrained using data from the literature and validated using a range of metabolic and sinusoidal length perturbation protocols. The placement of the MgADP binding step between two strongly-bound and force-generating states leads to the emergence of an unexpected effect on the force-MgADP curve, where the trend of the relationship (positive or negative) depends on the concentrations of the other metabolites and [H(+)]. The model is used to investigate the sensitivity of maximum force production to changes in metabolite concentrations during the development of ischemia.

Impact of copeptin on diagnosis of acute coronary syndrome

African Journals Online (AJOL)

Zeinab H. El Sayed

2014-03-17

Mar 17, 2014 ... the levels of copeptin, high-sensitivity cardiac troponin high ... The Egyptian Journal of Medical Human Genetics ... negative predictive value, which aids in early and safe ruling out of ... a standardized protocol in the National Heart Institute, Health ... Local ethics committee approved the study proto- col and ...

Anti-troponin I antibodies in renal transplant patients.

Science.gov (United States)

Nunes, José Pedro L; Sampaio, Susana; Cerqueira, Ana; Kaya, Ziya; Oliveira, Nuno Pardal

2015-02-01

To characterize the prevalence and clinical correlates of anti-troponin I antibodies in renal transplant patients. A group of 48 consecutive renal transplant patients under immunosuppressive therapy were studied. Anti-troponin I antibodies were measured and clinical data were retrieved. An anti-troponin I antibody titer renal transplant patients, and are not associated with the presence of clinical heart disease, but are associated with lack of statin therapy. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Cardiac Troponin Elevation Predicts Mortality in Patients Undergoing Orthotopic Liver Transplantation

Directory of Open Access Journals (Sweden)

David Snipelisky

2013-01-01

Full Text Available Introduction. While patients undergoing orthotopic liver transplantation (OLT have high cardiovascular event rates, preoperative risk stratification may not necessarily predict those susceptible patients. Troponin T (TnT may help predict patients at risk for cardiovascular complications. Methods. Consecutive patients undergoing OLT at Mayo Clinic in Florida between 1998 and 2010 who had TnT obtained within 10 days following surgery were included. Three groups were compared based on TnT level: (1 normal (TnT ≤0.01 ng/mL, (2 intermediate (TnT 0.02–0.11 ng/mL, and (3 elevated (TnT >0.11 ng/mL. Overall and cardiovascular mortality was assessed. Results. Of the 78 patients included, there was no difference in age, gender, severity of liver disease, and echocardiographic findings. Patients in the normal and intermediate TnT groups had a lower overall mortality rate (14.3% and 0%, resp. when compared with those with elevated TnT (50%; P=0.001. Patients in the elevated TnT group had a cardiovascular mortality rate of 37.5% compared with 1.4% in the other groups combined (P<0.01. The elevated TnT group had a much higher mortality rate when compared with those in the intermediate group (P<0.0001. Conclusion. TnT may accurately help risk stratify patients in the early postoperative setting to better predict cardiovascular complications.

Biomarkers of Cardiac Stress and Injury in Athletes: What Do They Mean?

Science.gov (United States)

Donnellan, Eoin; Phelan, Dermot

2018-04-01

Markers of myocardial stress, including troponin, creatine kinase, and brain natriuretic peptide are frequently elevated after endurance athletic pursuits. Here, we summarize the current literature pertaining to the potential mechanism of cardiac enzyme release in athletes and seek to determine the clinical implications of these findings. Recent studies have highlighted the potential adverse cardiac effects of long-term extreme endurance exercise. While troponin release occurs in a pattern distinct from ischemic damage, BNP release has been correlated with right ventricular dysfunction and is likely related to wall stress from prolonged increases in cardiac output. Higher intensity pre-race training regimes are associated with lower race-day enzyme release. While the holistic benefits of regular moderate exercise are indisputable, recent studies have raised concerns about the potential risks of extreme endurance exercise. Release of serum biomarkers suggesting myocardial damage was first described in the 1970s, yet our understanding of the implications of these findings remains incomplete. The mechanisms of release are complex but appear to be primarily physiological phenomena rather than pathologic.

Genotype-specific pathogenic effects in human dilated cardiomyopathy.

Science.gov (United States)

Bollen, Ilse A E; Schuldt, Maike; Harakalova, Magdalena; Vink, Aryan; Asselbergs, Folkert W; Pinto, Jose R; Krüger, Martina; Kuster, Diederik W D; van der Velden, Jolanda

2017-07-15

Mutations in genes encoding cardiac troponin I (TNNI3) and cardiac troponin T (TNNT2) caused altered troponin protein stoichiometry in patients with dilated cardiomyopathy. TNNI3 p.98trunc resulted in haploinsufficiency, increased Ca 2+ -sensitivity and reduced length-dependent activation. TNNT2 p.K217del caused increased passive tension. A mutation in the gene encoding Lamin A/C (LMNA p.R331Q ) led to reduced maximal force development through secondary disease remodelling in patients suffering from dilated cardiomyopathy. Our study shows that different gene mutations induce dilated cardiomyopathy via diverse cellular pathways. Dilated cardiomyopathy (DCM) can be caused by mutations in sarcomeric and non-sarcomeric genes. In this study we defined the pathogenic effects of three DCM-causing mutations: the sarcomeric mutations in genes encoding cardiac troponin I (TNNI3 p.98truncation ) and cardiac troponin T (TNNT2 p.K217deletion ; also known as the p.K210del) and the non-sarcomeric gene mutation encoding lamin A/C (LMNA p.R331Q ). We assessed sarcomeric protein expression and phosphorylation and contractile behaviour in single membrane-permeabilized cardiomyocytes in human left ventricular heart tissue. Exchange with recombinant troponin complex was used to establish the direct pathogenic effects of the mutations in TNNI3 and TNNT2. The TNNI3 p.98trunc and TNNT2 p.K217del mutation showed reduced expression of troponin I to 39% and 51%, troponin T to 64% and 53%, and troponin C to 73% and 97% of controls, respectively, and altered stoichiometry between the three cardiac troponin subunits. The TNNI3 p.98trunc showed pure haploinsufficiency, increased Ca 2+ -sensitivity and impaired length-dependent activation. The TNNT2 p.K217del mutation showed a significant increase in passive tension that was not due to changes in titin isoform composition or phosphorylation. Exchange with wild-type troponin complex corrected troponin protein levels to 83% of controls in the TNNI3

Cardioprotective Effects of Tualang Honey: Amelioration of Cholesterol and Cardiac Enzymes Levels

OpenAIRE

Khalil, Md. Ibrahim; Tanvir, E. M.; Afroz, Rizwana; Sulaiman, Siti Amrah; Gan, Siew Hua

2015-01-01

The present study was designed to investigate the cardioprotective effects of Malaysian Tualang honey against isoproterenol- (ISO-) induced myocardial infarction (MI) in rats by investigating changes in the levels of cardiac marker enzymes, cardiac troponin I (cTnI), triglycerides (TG), total cholesterol (TC), lipid peroxidation (LPO) products, and antioxidant defense system combined with histopathological examination. Male albino Wistar rats (n = 40) were pretreated orally with Tualang honey...

Frequency of exercise-induced ST-T-segment deviations and cardiac arrhythmias in recreational endurance athletes during a marathon race: results of the prospective observational Berlin Beat of Running study.

Science.gov (United States)

Herm, Juliane; Töpper, Agnieszka; Wutzler, Alexander; Kunze, Claudia; Krüll, Matthias; Brechtel, Lars; Lock, Jürgen; Fiebach, Jochen B; Heuschmann, Peter U; Haverkamp, Wilhelm; Endres, Matthias; Jungehulsing, Gerhard Jan; Haeusler, Karl Georg

2017-08-03

While regular physical exercise has many health benefits, strenuous physical exercise may have a negative impact on cardiac function. The 'Berlin Beat of Running' study focused on feasibility and diagnostic value of continuous ECG monitoring in recreational endurance athletes during a marathon race. We hypothesised that cardiac arrhythmias and especially atrial fibrillation are frequently found in a cohort of recreational endurance athletes. The main secondary hypothesis was that pathological laboratory findings in these athletes are (in part) associated with cardiac arrhythmias. Prospective observational cohort study including healthy volunteers. One hundred and nine experienced marathon runners wore a portable ECG recorder during a marathon race in Berlin, Germany. Athletes underwent blood tests 2-3 days prior, directly after and 1-2 days after the race. Overall, 108 athletes (median 48 years (IQR 45-53), 24% women) completed the marathon in 249±43 min. Blinded ECG analysis revealed abnormal findings during the marathon in 18 (16.8%) athletes. Ten (9.3%) athletes had at least one episode of non-sustained ventricular tachycardia, one of whom had atrial fibrillation; eight (7.5%) individuals showed transient ST-T-segment deviations. Abnormal ECG findings were associated with advanced age (OR 1.11 per year, 95% CI 1.01 to 1.23), while sex and cardiovascular risk profile had no impact. Directly after the race, high-sensitive troponin T was elevated in 18 (16.7%) athletes and associated with ST-T-segment deviation (OR 9.9, 95% CI 1.9 to 51.5), while age, sex and cardiovascular risk profile had no impact. ECG monitoring during a marathon is feasible. Abnormal ECG findings were present in every sixth athlete. Exercise-induced transient ST-T-segment deviations were associated with elevated high-sensitive troponin T (hsTnT) values. ClinicalTrials.gov NCT01428778; Results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article

Study of High Sensitive-CRP and Cardiac Marker Enzymes in Acute Coronary Syndrome

Directory of Open Access Journals (Sweden)

Srikrishna R,

2015-04-01

Full Text Available Background: Inflammation has been proposed as a contributor to different stages in the pathogenesis of Coronary Heart Disease (CHD. High sensitive C-Reactive Protein (hs-CRP, an acute-phase plasma protein synthesized by the liver, is the most extensively studied systemic marker of inflammation. Elevated hsCRP concentrations early in Acute Coronary Syndrome (ACS, prior to the tissue necrosis, may be a surrogate marker for cardiovascular co-morbidities. The cardiac marker enzymes Creatine Kinase myocardial bound (CK-MB, Aspartate Aminotransferase (AST and lactate dehydrogenase (LDH have been known to be increased in coronary artery diseases. Objective: The aim of the study was to measure hs-CRP levels and other cardiac marker enzymes in ACS patients and to compare the levels of hs-CRP with other cardiac marker enzymes between ST Elevation Myocardial Infarction (STEMI and Non-ST Elevation Myocardial Infarction (NSTEMI patients. Material and Methods: The study group consisted of 207 consecutive patients admitted to Sri Siddhartha Medical College Hospital within the first 6 hours from the onset of chest pain. Patients were diagnosed as Unstable Angina (UA, (n=84; STEMI (n=63 and NSTEMI (n=60. ACS patients were compared with 211 healthy age and sex matched controls. Hs-CRP, CK-MB, AST and LDH levels were measured by standard methods in both groups at baseline and forcases at 36-48 hours i.e. Peak levels. Results: ACS patients had significantly (p<0.05 higher levels of hs-CRP, CKMB, AST and LDH in comparison to controls at baseline. Hs-CRP, CK-MB, AST and LDH levels were significantly higher in STEMI patients compared to NSTEMI patients (p<0.05 at baseline. There was a significant difference regarding peak hs-CRP levels between the two groups, as STEMI patients had significantly higher peak hs-CRP levels compared to NSTEMI patients (p<0.05. Conclusion: STEMI patients have significantly higher peak hsCRP levels compared to NSTEMI patients. These data

Effect of a low glycemic index diet versus a high-cereal fibre diet on markers of subclinical cardiac injury in healthy individuals with type 2 diabetes mellitus: An exploratory analysis of a randomized dietary trial.

Science.gov (United States)

Ha, Vanessa; Viguiliouk, Effie; Kendall, Cyril W C; Balachandran, Bashyam; Jenkins, David J A; Kavsak, Peter A; Sievenpiper, John L

2017-12-01

Markers of subclinical cardiac injury are elevated in individuals with type 2 diabetes mellitus (T2DM) compared to healthy individuals. Low glycemic index (LGI) diets may improve both diabetes and cardiovascular risk but their effects on cardiac injury and fibrosis have not been previously studied. To test the effect of a LGI diet on markers of subclinical cardiac injury and fibrosis, we assessed the effect of a LGI compared with a high-cereal fibre diet on high-sensitivity cardiac troponin I (hs-cTnI) and galectin-3 in otherwise healthy individuals with T2DM in an exploratory analysis of a completed randomized trial. A total of 201 participants completed the trial and had measurements of hs-cTnI and galectin-3 at baseline and at trial completion. Participants were randomized to follow a LGI or a high-cereal fibre diet over a 6-month period. Treatment differences were tested using Analysis of Covariance (ANCOVA) with sex, baseline values, and diet x sex interaction included as covariates. In a completer's analysis, no significant differences were observed for change in hs-cTnI (-0.16ng/L vs. -0.22ng/L, p=0.713) and galectin-3 levels (0.64μg/L vs. 0.14μg/L, p=0.166) when a LGI diet was compared to a high-cereal fibre diet. The effect of a LGI diet was similar to a high-cereal fibre diet on hs-cTnI and galectin-3 levels in otherwise healthy individuals with T2DM over a 6-month period. Nevertheless, in the absence of any adverse effects, LGI diets remain an option for diabetes and cardiovascular disease risk management. ClinicalTrials.gov identifier: NCT00438698. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Use of Cardiac Injury Markers in the Postmortem Diagnosis of Sudden Cardiac Death.

Science.gov (United States)

Carvajal-Zarrabal, Octavio; Hayward-Jones, Patricia M; Nolasco-Hipolito, Cirilo; Barradas-Dermitz, Dulce Ma; Calderón-Garcidueñas, Ana Laura; López-Amador, Noé

2017-09-01

In the daily practice of forensic pathology, sudden cardiac death (SCD) is a diagnostic challenge. Our aim was to determine the usefulness of blood biomarkers [creatine kinase CK-MB, myoglobin, troponins I and T (cTn-I and T), and lactate dehydrogenase] measured by immunoassay technique, in the postmortem diagnosis of SCD. Two groups were compared, 20 corpses with SCD and 8 controls. Statistical significance was determined by variance analysis procedures, with a post hoc Tukey multiple range test for comparison of means (p < 0.05). SCD cases showed significantly higher levels (p < 0.05) of cTn-T and cTn-I compared to the control group. Although only cases within the first 8 h of postmortem interval were included, and the control group consisted mainly of violent death cases, our results suggest that blood troponin levels may be useful to support a diagnosis of SCD. © 2017 American Academy of Forensic Sciences.

How does pressure overload cause cardiac hypertrophy and dysfunction? High-ouabain affinity cardiac Na+ pumps are crucial.

Science.gov (United States)

Blaustein, Mordecai P

2017-11-01

Left ventricular hypertrophy is frequently observed in hypertensive patients and is believed to be due to the pressure overload and cardiomyocyte stretch. Three recent reports on mice with genetically engineered Na + pumps, however, have demonstrated that cardiac ouabain-sensitive α 2 -Na + pumps play a key role in the pathogenesis of transaortic constriction-induced hypertrophy. Hypertrophy was delayed/attenuated in mice with mutant, ouabain-resistant α 2 -Na + pumps and in mice with cardiac-selective knockout or transgenic overexpression of α 2 -Na + pumps. The latter, seemingly paradoxical, findings can be explained by comparing the numbers of available (ouabain-free) high-affinity (α 2 ) ouabain-binding sites in wild-type, knockout, and transgenic hearts. Conversely, hypertrophy was accelerated in α 2 -ouabain-resistant (R) mice in which the normally ouabain-resistant α 1 -Na + pumps were mutated to an ouabain-sensitive (S) form (α 1 S/S α 2 R/R or "SWAP" vs. wild-type or α 1 R/R α 2 S/S mice). Furthermore, transaortic constriction-induced hypertrophy in SWAP mice was prevented/reversed by immunoneutralizing circulating endogenous ouabain (EO). These findings show that EO and its receptor, ouabain-sensitive α 2 , are critical factors in pressure overload-induced cardiac hypertrophy. This complements reports linking elevated plasma EO to hypertension, cardiac hypertrophy, and failure in humans and elucidates the underappreciated role of the EO-Na + pump pathway in cardiovascular disease. Copyright © 2017 the American Physiological Society.

Cardiac Dysfunction in a Porcine Model of Pediatric Malnutrition

DEFF Research Database (Denmark)

Fabiansen, Christian; Lykke, Mikkel; Hother, Anne-Louise

2015-01-01

BACKGROUND: Half a million children die annually of severe acute malnutrition and cardiac dysfunction may contribute to the mortality. However, cardiac function remains poorly examined in cases of severe acute malnutrition. OBJECTIVE: To determine malnutrition-induced echocardiographic disturbances...... and longitudinal changes in plasma pro-atrial natriuretic peptide and cardiac troponin-T in a pediatric porcine model. METHODS AND RESULTS: Five-week old piglets (Duroc-x-Danish Landrace-x-Yorkshire) were fed a nutritionally inadequate maize-flour diet to induce malnutrition (MAIZE, n = 12) or a reference diet...... groups. The myocardial performance index was 86% higher in MAIZE vs AGE-REF (pMalnutrition associates with cardiac dysfunction in a pediatric porcine model by increased myocardial performance index and pro-atrial natriuretic peptide...

Sensitivity and Specificity of Cardiac Tissue Discrimination Using Fiber-Optics Confocal Microscopy.

Science.gov (United States)

Huang, Chao; Sachse, Frank B; Hitchcock, Robert W; Kaza, Aditya K

2016-01-01

Disturbances of the cardiac conduction system constitute a major risk after surgical repair of complex cases of congenital heart disease. Intraoperative identification of the conduction system may reduce the incidence of these disturbances. We previously developed an approach to identify cardiac tissue types using fiber-optics confocal microscopy and extracellular fluorophores. Here, we applied this approach to investigate sensitivity and specificity of human and automated classification in discriminating images of atrial working myocardium and specialized tissue of the conduction system. Two-dimensional image sequences from atrial working myocardium and nodal tissue of isolated perfused rodent hearts were acquired using a fiber-optics confocal microscope (Leica FCM1000). We compared two methods for local application of extracellular fluorophores: topical via pipette and with a dye carrier. Eight blinded examiners evaluated 162 randomly selected images of atrial working myocardium (n = 81) and nodal tissue (n = 81). In addition, we evaluated the images using automated classification. Blinded examiners achieved a sensitivity and specificity of 99.2 ± 0.3% and 98.0 ± 0.7%, respectively, with the dye carrier method of dye application. Sensitivity and specificity was similar for dye application via a pipette (99.2 ± 0.3% and 94.0 ± 2.4%, respectively). Sensitivity and specificity for automated methods of tissue discrimination were similarly high. Human and automated classification achieved high sensitivity and specificity in discriminating atrial working myocardium and nodal tissue. We suggest that our findings facilitate clinical translation of fiber-optics confocal microscopy as an intraoperative imaging modality to reduce the incidence of conduction disturbances during surgical correction of congenital heart disease.

Indirect imaging of cardiac-specific transgene expression using a bidirectional two-step transcriptional amplification strategy

DEFF Research Database (Denmark)

Chen, I Y; Gheysens, O; Ray, S

2010-01-01

in a cardiac cell line and the myocardium, while minimizing expression in non-cardiac cell lines and the liver. In vitro, the TSTA system significantly enhanced cTnT-mediated reporter gene expression with moderate preservation of cardiac specificity. After intramyocardial and hydrodynamic tail vein delivery...... genes, firefly luciferase (fluc) and Renilla luciferase (hrluc), driven by the cardiac troponin T (cTnT) promoter. The vector was characterized in vitro and in living mice using luminometry and bioluminescence imaging to assess its ability to mediate strong, correlated reporter gene expression...

Troponin T and N-terminal pro B-Type natriuretic peptide and presence of coronary artery disease

DEFF Research Database (Denmark)

Mouridsen, Mette R; Sajadieh, Ahmad; Carlsen, Christian M

2015-01-01

BACKGROUND: We tested the effects of exercise intensity, sampling intervals, degree of coronary artery stenosis, and demographic factors on circulating N-terminal pro B-Type natriuretic peptide (NT-pro-BNP) and cardiac Troponin T (cTnT) in subjects suspected of coronary artery disease (CAD). MATE...... = 0.4067 p = 0.046). CONCLUSIONS: Baseline cTnT and ΔcTnT were found to be independently associated with CAD and also with exercise intensity in stable chest pain subjects. These properties were not identified for NT-pro-BNP....

Correlation between Serum High Sensitivity CRP Level and Inhospital Cardiac Events in the Patients with Unstable Angina

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H. Kazerani

2007-10-01

Full Text Available Introduction & Objective: Several studies have been performed to evaluate correlation of serum high sensitivity CRP (hs-CRP level with the prognosis of the patients with diagnosis of unstable angina, and by now different results were reported. The aim of this study was to assess correlation between serum hs-CRP level and inhospital prognosis and cardiac events in the patients with unstable angina. Materials & Methods: This descriptive analytic study was performed from Sep 2004 till Feb 2006 in Shahid Beheshti hospital. Kermanshah, Iran. Sera were collected from 250 patients for hs-CRP measurement. Exclusion criteria were: acute ST elevation MI, non ST elevation MI, patients with history of recent infection, patients with recent trauma and patients with serum high sensitive CRP level more than 10 mg/lit. Patients were divided into two groups, first group whose serum hs-CRP level was less than 3 mg/lit and second group whose serum hs-CRP level was between 3 and 10 mg/lit. They were followed for recurrent chest pain, arrhythmias, pulmonary edema, acute myocardial infarction and in hospital death. Results were analyzed using x² and t-test. Results: Mean age were 57±7.8 and 58±11.5 years in first group and second group respectively. There was statistically significant difference in some cardiac complications such as dyspnea, duration of hospitalization, recurrent chest pain, CCU admission (p<0.001 and in hospital myocardial infarction (p=0.03, between two groups. Some complications did not have significant difference such as pulmonary edema, cardiogenic shock, arrhythmia, S3, S4 and pulmonary rates .There was no mortality in both groups. Conclusion: According to the results, we can use serum hs-CRP level for risk stratification in the patients with diagnosis of unstable angina. Obviously the patients with high serum hs-CRP level need more attention whether early invasive management help these patients, may be the matter of later studies.

Major depressive disorder, anxiety disorders, and cardiac biomarkers in subjects at high risk of obstructive sleep apnea.

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Einvik, Gunnar; Hrubos-Strøm, Harald; Randby, Anna; Nordhus, Inger Hilde; Somers, Virend K; Omland, Torbjørn; Dammen, Toril

2011-06-01

Cardiac biomarkers may be valuable when exploring potential mechanisms for the association between cardiovascular disease and psychiatric disorders. In subjects at increased risk for obstructive sleep apnea, we examined whether major depressive disorder (MDD), anxiety disorders, or the combination of these was associated with circulating C-reactive protein (CRP), cardiac troponin T (cTnT), or heart rate variability (HRV). From the Akershus Sleep Apnea Project, 290 participants were assessed for MDD or any anxiety disorder by a physician using the Structured Clinical Interview for DSM-IV. Fasting blood samples were analyzed with high-sensitivity assays for CRP, cTnT, and HRV calculated from a Holter recording. Age, sex, hypertension, diabetes, hyperlipidemia, obesity, smoking, apnea-hypopnea index, and previous cardiovascular disease were adjusted for. The CRP levels (median [interquartile range], mg/L) were higher in depressive (2.7 [1.1-5.8]) versus nondepressive (1.3 [0.7-3.1], p = .02) and in anxious (2.8 [0.9-5.2]) versus nonanxious (1.3 [0.7-3.1], p = .01). MDD was independently associated with CRP (unstandardized β = 0.387, p = .04), but anxiety was not (unstandardized β = 0.298, p = .09). The CRP level was highest in subjects with comorbid MDD and anxiety (3.4 [1.1-7.8]). The unadjusted and adjusted odds ratios (95% confidence interval) for having measurable cTnT (> 3 ng/L) were 0.49 (0.24-1.07) and 0.92 (0.31-2.67) for MDD versus nondepressive and 0.38 (0.18-0.80) and 0.61 (0.30-2.05) for anxiety versus nonanxiety, respectively. HRV did not vary between groups. Although CRP was increased both in MDD and anxiety disorders, patients with comorbid MDD and anxiety may be particularly prone to increased systemic inflammation. Neither MDD nor anxiety disorders were associated with low-level myocardial damage or HRV.

Proposal for the use in emergency departments of cardiac troponins measured with the latest generation methods in patients with suspected acute coronary syndrome without persistent ST-segment elevation

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Ivo Casagranda

2013-10-01

Full Text Available The purpose of this document is to develop recommendations on the use of the latest generation of cardiac troponins in emergency room settings for the diagnosis of myocardial infarction in patients with suspected acute coronary syndrome without persistent ST-segment elevation (NSTE-ACS. The main points which have been addressed reaching a consensus are: i suitability and appropriateness of the terminology; ii appropriateness of the request; iii confirmation of the diagnosis of myocardial infarction (rule-in; iv exclusion of the diagnosis of myocardial infarction (rule-out. Each point has been analyzed by taking into account the evidence presented in medical publications. Recommendations were developed using the criteria adopted by the European Society of Cardiology and the American Heart Association/American College of Cardiology. Each point of the recommendation was submitted for validation to an external audit by a Group of Experts (named above.

Troponin release following endurance exercise: is inflammation the cause? a cardiovascular magnetic resonance study

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O'Hanlon Rory

2010-07-01

Full Text Available Abstract Background The aetiology and clinical significance of troponin release following endurance exercise is unclear but may be due to transient myocardial inflammation. Cardiovascular magnetic resonance (CMR affords us the opportunity to evaluate the presence of myocardial inflammation and focal fibrosis and is the ideal imaging modality to study this hypothesis. We sought to correlate the relationship between acute bouts of ultra endurance exercise leading to cardiac biomarkers elevation and the presence of myocardial inflammation and fibrosis using CMR. Methods 17 recreation athletes (33.5 +/- 6.5 years were studied before and after a marathon run with troponin, NTproBNP, and CMR. Specific imaging parameters to look for inflammation included T2 weighted images, and T1 weighted spin-echo images before and after an intravenous gadolinium-DTPA to detect myocardial hyperemia secondary to inflammation. Late gadolinium imaging was performed (LGE to detect any focal regions of replacement fibrosis. Results Eleven of the 17 participant had elevations of TnI above levels of cut off for myocardial infarction 6 hrs after the marathon (0.075 +/- 0.02, p = 0.007. Left ventricular volumes were reduced post marathon and a small increase in ejection fraction was noted (64+/- 1% pre, 67+/- 1.2% post, P = 0.014. Right ventricular volumes, stroke volume, and ejection fraction were unchanged post marathon. No athlete fulfilled criteria for myocardial inflammation based on current criteria. No regions of focal fibrosis were seen in any of the participants. Conclusion Exercise induced cardiac biomarker release is not associated with any functional changes by CMR or any detectable myocardial inflammation or fibrosis.

Ascending-ramp biphasic waveform has a lower defibrillation threshold and releases less troponin I than a truncated exponential biphasic waveform.

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Huang, Jian; Walcott, Gregory P; Ruse, Richard B; Bohanan, Scott J; Killingsworth, Cheryl R; Ideker, Raymond E

2012-09-11

We tested the hypothesis that the shape of the shock waveform affects not only the defibrillation threshold but also the amount of cardiac damage. Defibrillation thresholds were determined for 11 waveforms-3 ascending-ramp waveforms, 3 descending-ramp waveforms, 3 rectilinear first-phase biphasic waveforms, a Gurvich waveform, and a truncated exponential biphasic waveform-in 6 pigs with electrodes in the right ventricular apex and superior vena cava. The ascending, descending, and rectilinear waveforms had 4-, 8-, and 16-millisecond first phases and a 3.5-millisecond rectilinear second phase that was half the voltage of the first phase. The exponential biphasic waveform had a 60% first-phase and a 50% second-phase tilt. In a second study, we attempted to defibrillate after 10 seconds of ventricular fibrillation with a single ≈30-J shock (6 pigs successfully defibrillated with 8-millisecond ascending, 8-millisecond rectilinear, and truncated exponential biphasic waveforms). Troponin I blood levels were determined before and 2 to 10 hours after the shock. The lowest-energy defibrillation threshold was for the 8-milliseconds ascending ramp (14.6±7.3 J [mean±SD]), which was significantly less than for the truncated exponential (19.6±6.3 J). Six hours after shock, troponin I was significantly less for the ascending-ramp waveform (0.80±0.54 ng/mL) than for the truncated exponential (1.92±0.47 ng/mL) or the rectilinear waveform (1.17±0.45 ng/mL). The ascending ramp has a significantly lower defibrillation threshold and at ≈30 J causes 58% less troponin I release than the truncated exponential biphasic shock. Therefore, the shock waveform affects both the defibrillation threshold and the amount of cardiac damage.

Midregional-proAtrial Natriuretic Peptide and High Sensitive Troponin T Strongly Predict Adverse Outcome in Patients Undergoing Percutaneous Repair of Mitral Valve Regurgitation.

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Jochen Wöhrle

Full Text Available It is not known whether biomarkers of hemodynamic stress, myocardial necrosis, and renal function might predict adverse outcome in patients undergoing percutaneous repair of severe mitral valve insufficiency. Thus, we aimed to assess the predictive value of various established and emerging biomarkers for major adverse cardiovascular events (MACE in these patients.Thirty-four patients with symptomatic severe mitral valve insufficiency with a mean STS-Score for mortality of 12.6% and a mean logistic EuroSCORE of 19.7% undergoing MitraClip therapy were prospectively included in this study. Plasma concentrations of mid regional-proatrial natriuretic peptide (MR-proANP, Cystatin C, high-sensitive C-reactive protein (hsCRP, high-sensitive troponin T (hsTnT, N-terminal B-type natriuretic peptide (NT-proBNP, galectin-3, and soluble ST-2 (interleukin 1 receptor-like 1 were measured directly before procedure. MACE was defined as cardiovascular death and hospitalization for heart failure (HF.During a median follow-up of 211 days (interquartile range 133 to 333 days, 9 patients (26.5% experienced MACE (death: 7 patients, rehospitalization for HF: 2 patients. Thirty day MACE-rate was 5.9% (death: 2 patients, no rehospitalization for HF. Baseline concentrations of hsTnT (Median 92.6 vs 25.2 ng/L, NT-proBNP (Median 11251 vs 1974 pg/mL and MR-proANP (Median 755.6 vs 318.3 pmol/L, all p<0.001 were clearly higher in those experiencing an event vs event-free patients, while other clinical variables including STS-Score and logistic EuroSCORE did not differ significantly. In Kaplan-Meier analyses, NT-proBNP and in particular hsTnT and MR-proANP above the median discriminated between those experiencing an event vs event-free patients. This was further corroborated by C-statistics where areas under the ROC curve for prediction of MACE using the respective median values were 0.960 for MR-proANP, 0.907 for NT-proBNP, and 0.822 for hsTnT.MR-proANP and hsTnT strongly

Factors contributing to troponin exchange in myofibrils and in solution.

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She, M; Trimble, D; Yu, L C; Chalovich, J M

2000-01-01

The troponin complex in a muscle fiber can be replaced with exogenous troponin by using a gentle exchange procedure in which the actin-tropomyosin complex is never devoid of a full complement of troponin (Brenner et al. (1999) Biophys J 77: 2677-2691). The mechanism of this exchange process and the factors that influence this exchange are poorly understood. In this study, the exchange process has now been examined in myofibrils and in solution. In myofibrils under rigor conditions, troponin exchange occurred preferentially in the region of overlap between actin and myosin when the free Ca2+ concentration was low. At higher concentrations of Ca2+, the exchange occurred uniformly along the actin. Ca2+ also accelerated troponin exchange in solution but the effect of S1 could not be confirmed in solution experiments. The rate of exchange in solution was insensitive to moderate changes in pH or ionic strength. Increasing the temperature resulted in a two-fold increase in rate with each 10 degrees C increase in temperature. A sequential two step model of troponin binding to actin-tropomyosin could simulate the observed association and dissociation transients. In the absence of Ca2+ or rigor S1, the following rate constants could describe the binding process: k1 = 7.12 microM(-1) s(-1), k(-1) = 0.65 s(-1), k2 = 0.07 s(-1), k(-2) = 0.0014 s(-1). The slow rate of detachment of troponin from actin (k(-2)) limits the rate of exchange in solution and most likely contributes to the slow rate of exchange in fibers.

Perioperative Rosuvastatin in Cardiac Surgery.

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Zheng, Zhe; Jayaram, Raja; Jiang, Lixin; Emberson, Jonathan; Zhao, Yan; Li, Qi; Du, Juan; Guarguagli, Silvia; Hill, Michael; Chen, Zhengming; Collins, Rory; Casadei, Barbara

2016-05-05

Complications after cardiac surgery are common and lead to substantial increases in morbidity and mortality. Meta-analyses of small randomized trials have suggested that perioperative statin therapy can prevent some of these complications. We randomly assigned 1922 patients in sinus rhythm who were scheduled for elective cardiac surgery to receive perioperative rosuvastatin (at a dose of 20 mg daily) or placebo. The primary outcomes were postoperative atrial fibrillation within 5 days after surgery, as assessed by Holter electrocardiographic monitoring, and myocardial injury within 120 hours after surgery, as assessed by serial measurements of the cardiac troponin I concentration. Secondary outcomes included major in-hospital adverse events, duration of stay in the hospital and intensive care unit, left ventricular and renal function, and blood biomarkers. The concentrations of low-density lipoprotein cholesterol and C-reactive protein after surgery were lower in patients assigned to rosuvastatin than in those assigned to placebo (PSTICS ClinicalTrials.gov number, NCT01573143.).

Unexpected Cardiac Computed Tomography Findings in Patients With Postoperative Myocardial Injury.

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Grobben, Remco B; van Waes, Judith A R; Leiner, Tim; Peelen, Linda M; de Borst, Gert Jan; Vogely, Henri C; Grobbee, Diederick E; Doevendans, Pieter A; van Klei, Wilton A; Nathoe, Hendrik M

2018-05-01

Postoperative myocardial injury (PMI) is a strong predictor of mortality after noncardiac surgery. PMI is believed to be attributable to coronary artery disease (CAD), yet its etiology is largely unclear. We aimed to quantify the prevalence of significant CAD in patients with and without PMI using coronary computed tomography angiography (CCTA). This prospective cohort study included patients of 60 years or older without a history of cardiac disease and with and without PMI after intermediate- to high-risk noncardiac surgery. PMI was defined as any serum troponin I level ≥60 ng/L on the first 3 postoperative days. Main exclusion criteria were known cardiac disease and postoperative ischemic symptoms or electrocardiography abnormalities. Noninvasive imaging consisted of a postoperative CCTA. Main outcome was CAD defined as >50% coronary stenosis on CCTA. The analysis included 66 patients. Median peak troponin levels in the PMI (n = 46) and control group (n = 20) were 150 (interquartile range, 120-298) vs 15 (interquartile range, 10-31) ng/L (P PMI (50%) vs 3 without PMI (15%; relative risk, 3.3; 95% confidence interval, 1.1-9.8). Remarkably, pulmonary embolism was present in 15 patients with PMI (33%) versus in 4 without PMI (20%; relative risk, 1.6; 95% confidence interval, 0.6-4.3). None of the patients died within 30 days. In patients without a history of cardiac disease, PMI after noncardiac surgery was associated with CAD. In addition, a clinically silent pulmonary embolism was found in one-third of patients with PMI. This urges further research to improve clinical workup using imaging and may have important clinical implications.

High prevalence of Arginine to Glutamine Substitution at 98, 141 and 162 positions in Troponin I (TNNI3 associated with hypertrophic cardiomyopathy among Indians

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Rani Deepa

2012-08-01

Full Text Available Abstract Background Troponin I (TNNI3 is the inhibitory subunit of the thin filament regulatory complex Troponin, which confers calcium-sensitivity to striated muscle actomyosin ATPase activity. Mutations (2-7% in this gene had been reported in hypertrophic cardiomyopathy patients (HCM. However, the frequencies of mutations and associated clinical presentation have not been established in cardiomyopathy patients of Indian origin, hence we have undertaken this study. Methods We have sequenced all the exons, including the exon-intron boundaries of TNNI3 gene in 101 hypertrophic cardiomyopathy patients (HCM, along with 160 healthy controls, inhabited in the same geographical region of southern India. Results Our study revealed a total of 16 mutations. Interestingly, we have observed Arginine to Glutamine (R to Q mutation at 3 positions 98, 141 and 162, exclusively in HCM patients with family history of sudden cardiac death. The novel R98Q was observed in a severe hypertrophic obstructive cardiomyopathy patient (HOCM. The R141Q mutation was observed in two familial cases of severe asymmetric septal hypertrophy (ASH++. The R162Q mutation was observed in a ASH++ patient with mean septal thickness of 29 mm, and have also consists of allelic heterogeneity by means of having one more synonymous (E179E mutation at g.4797: G → A: in the same exon 7, which replaces a very frequent codon (GAG: 85% with a rare codon (GAA: 14%. Screening for R162Q mutation in all the available family members revealed its presence in 9 individuals, including 7 with allelic heterogeneity (R162Q and E179E of which 4 were severely affected. We also found 2 novel SNPs, (g.2653; G → A and g.4003 C → T exclusively in HCM, and in silico analysis of these SNPs have predicted to cause defect in recognition/binding sites for proteins responsible for proper splicing. Conclusion Our study has provided valuable information regarding the prevalence of TNNI3 mutations in

Novel Risk Stratification Assays for Acute Coronary Syndrome.

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Ahmed, Haitham M; Hazen, Stanley L

2017-08-01

Since identification of aspartate aminotransferase as the first cardiac biomarker in the 1950s, there have been a number of new markers used for myocardial damage detection over the decades. There have also been several generations of troponin assays, each with progressively increasing sensitivity for troponin detection. Accordingly, the "standard of care" for myocardial damage detection continues to change. The purpose of this paper is to review the clinical utility, biological mechanisms, and predictive value of these various biomarkers in contemporary clinical studies. As of this writing, a fifth "next" generation troponin assay has now been cleared by the US Food and Drug Administration for clinical use in the USA for subjects presenting with suspected acute coronary syndromes. Use of these high-sensitivity assays has allowed for earlier detection of myocardial damage as well as greater negative predictive value for infarction after only one or two serial measurements. Recent algorithms utilizing these assays have allowed for more rapid rule-out of myocardial infarction in emergency department settings. In this review, we discuss novel assays available for the risk assessment of subjects presenting with chest pain, including both the "next generation" cardiac troponin assays as well as other novel biomarkers. We review the biological mechanisms for these markers, and explore the positive and negative predictive value of the assays in clinical studies, where reported. We also discuss the potential use of these new markers within the context of future clinical care in the modern era of higher sensitivity troponin testing. Finally, we discuss advances in new platforms (e.g., mass spectrometry) that historically have not been considered for rapid in vitro diagnostic capabilities, but that are taking a larger role in clinical diagnostics, and whose prognostic value and power promise to usher in new markers with potential for future clinical utility in acute coronary

Novel Toll-like receptor-4 deficiency attenuates trastuzumab (Herceptin induced cardiac injury in mice

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Yousif Nasser

2011-10-01

Full Text Available Abstract Background Cardiac inflammation and generation of oxidative stress are known to contribute to trastuzumab (herceptin induced cardiac toxicity. Toll-like receptors (TLRs are a part of the innate immune system and are involved in cardiac stress reactions. Since TLR4 might play a relevant role in cardiac inflammatory signaling, we investigated whether or not TLR4 is involved in trastuzumab induced cardiotoxicity. Methods Seven days after a single injection of herceptin (2 mg/kg; i.p., left ventricular pressure volume loops were measured in HeN compotent (TLR4+/+ and HeJ mutant (TLR4-/- treated with trastuzumab and control mice. Immunofluorescent staining for monocyte infiltration and analyses of plasma by (ELISAs for different chemokines including: MCP-1and tumor necrosis factor-α (TNF-α, Western immunoblotting assay for ICAM-1, and used troponin I for cardiac injury marker. Results Trastuzumab injection resulted in an impairment of left ventricular function in TLR-4 competent (HeN, in contrast TLR4-/- trastuzumab mice showed improved left ventricular function EF%, CO; p -/-; p -/-, marked reduction of myocardial troponin-I levels in TLR4-deficient mice. Data are presented as means ± SE; n = 8 in each group p Conclusions Treatment with trastuzumab induces an inflammatory response that contributes to myocardial tissue TLR4 mediates chemokine expression (TNF-α, MCP-1and ICAM-1, so in experimental animals TLR4 deficiency improves left ventricular function and attenuates pathophysiological key mechanisms in trastuzumab induced cardiomyopathy.

Pharmacodynamic modeling of cardiac biomarkers in breast cancer patients treated with anthracycline and trastuzumab regimens

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de Vries Schultink, Aurelia H M; Boekhout, Annelies H; Gietema, Jourik A; Burylo, Artur M; Dorlo, Thomas P C; van Hasselt, J G Coen; Schellens, Jan H M; Huitema, Alwin D R

Trastuzumab is associated with cardiotoxicity, manifesting as a decrease of the left-ventricular ejection fraction (LVEF). Administration of anthracyclines prior to trastuzumab increases risk of cardiotoxicity. High-sensitive troponin T and N-terminal-pro-brain natriuretic peptide (NT-proBNP) are

The use of cell cycle arrest biomarkers in the early detection of acute kidney injury. Is this the new renal troponin?

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Ortega, Luis M; Heung, Michael

2018-04-05

Acute kidney injury (AKI) has a high prevalence in critical care patients. Early detection might prevent patients from developing chronic kidney disease and requirement for renal replacement therapy. If we compare AKI with acute coronary syndrome, in which an increase in cardiac troponin may trigger early diagnosis and therapeutic intervention, we could extrapolate a similar technique in patients with early AKI without changes in urinary frequency or serum creatinine. The objective is to identify biomarker-positive, creatinine-negative patients that would allow therapeutic interventions to be initiated before finding changes in serum creatinine, preventing kidney damage. Tissue inhibitor of metalloproteinase 2 and insulin-like growth factor binding protein 7 are cell cycle arrest biomarkers that have demonstrated, in recent clinical trials, to have good sensitivity and specificity for early detection of AKI. Other recent studies have shown that the joint use of these biomarkers with serum creatinine and urine production could improve the prognosis of AKI in critical patients. The application of these biomarkers in clinical practice would enable the early identification of patients at risk of AKI, establishing interventions that would improve the survival of renal function. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Three-dimensional Speckle Tracking Echocardiography in Light Chain Cardiac Amyloidosis: Examination of Left and Right Ventricular Myocardial Mechanics Parameters.

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Urbano-Moral, Jose Angel; Gangadharamurthy, Dakshin; Comenzo, Raymond L; Pandian, Natesa G; Patel, Ayan R

2015-08-01

The study of myocardial mechanics has a potential role in the detection of cardiac involvement in patients with amyloidosis. This study aimed to characterize 3-dimensional-speckle tracking echocardiography-derived left and right ventricular myocardial mechanics in light chain amyloidosis and examine their relationship with brain natriuretic peptide. In patients with light chain amyloidosis, left ventricular longitudinal and circumferential strain (n=40), and right ventricular longitudinal strain and radial displacement (n=26) were obtained by 3-dimensional-speckle tracking echocardiography. Brain natriuretic peptide levels were determined. All myocardial mechanics measurements showed differences when compared by brain natriuretic peptide level tertiles. Left and right ventricular longitudinal strain were highly correlated (r=0.95, P<.001). Left ventricular longitudinal and circumferential strain were reduced in patients with cardiac involvement (-9±4 vs -16±2; P<.001, and -24±6 vs -29±4; P=.01, respectively), with the most prominent impairment at the basal segments. Right ventricular longitudinal strain and radial displacement were diminished in patients with cardiac involvement (-9±3 vs -17±3; P<.001, and 2.7±0.8 vs 3.8±0.3; P=.002). On multivariate analysis, left ventricular longitudinal strain was associated with the presence of cardiac involvement (odds ratio = 1.6; 95% confidence interval, 1.04 to 2.37; P=.03) independent of the presence of brain natriuretic peptide and troponin I criteria for cardiac amyloidosis. Three-dimensional-speckle tracking echocardiography-derived left and right ventricular myocardial mechanics are increasingly altered as brain natriuretic peptide increases in light chain amyloidosis. There appears to be a strong association between left ventricular longitudinal strain and cardiac involvement, beyond biomarkers such as brain natriuretic peptide and troponin I. Copyright © 2015 Sociedad Española de Cardiología. Published by

Overexpression of Cardiac-Specific Kinase TNNI3K Promotes Mouse Embryonic Stem Cells Differentiation into Cardiomyocytes.

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Wang, Yin; Wang, Shi-Qiang; Wang, Li-Peng; Yao, Yu-Hong; Ma, Chun-Yan; Ding, Jin-Feng; Ye, Jue; Meng, Xian-Min; Li, Jian-Jun; Xu, Rui-Xia

2017-01-01

Backgroud/Aims: The biological function of cardiac troponin I-interacting kinase (TNNI3K), a cardiac-specific functional kinase, is largely unknown. We investigated the effect of human TNNI3K (hTNNI3K) on the differentiation of mouse embryonic stem cells (mESCs) into cardiomyocytes. First, the time-space expression of endogenous Tnni3k was detected by real-time polymerase chain reaction (PCR) and western blotting at 16 different time-points over a period of 28 days. Further, action potentials and calcium current with/without 5 µM nifedipine were measured by patch clamp for mESC-derived cardiomyocytes. HTNNI3K and mouse-derived siRNA were transfected into mESC using lentivirus vector to induce hTNNI3K overexpression and knock-down, respectively. The number of troponin-T (cTnT) positive cells was greater in the group with TNNI3K overexpression as compared to that in control group, while less such cells were detected in the mTnni3k knock-down group as evaluated on flow cytometry (FCM) and ImageXpress Micro system. After upregulation of connexin43, cardiac troponin-I (Ctni), Ctni, Gata4 were detected in mESCs with TNNI3K overexpression; however, overexpression of α-Actinin and Mlc2v was not detected. Interestingly, Ctnt, connexin40 and connexin45, the markers of ventricular, atrial, and pacemaker cells, respectively, were detected in by real-time PCR in TNNI3K overexpression group. our study indicated that TNNI3K overexpression promoted mESC differentiating into beating cardiomyocytes and induced up-regulating expression of cTnT by PKCε signal pathway, which suggested a modulation of TNNI3K activity as a potential therapeutic approach for ischemic cardiac disease. © 2017 The Author(s) Published by S. Karger AG, Basel.

Diagnostic value of mean platelet volume (MPV) to troponin T inpatients with acute coronary syndrome

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Aryanto, D.; Isnanta, R.; Safri, Z.; Hasan, R.

2018-03-01

Acute Coronary Syndrome (ACS) is used to describe the spectrum of coronary artery disease (CAD). Troponin T is the determinant of the most sensitive marker of ACS, but there aren’t all hospitals have this because of expensiveness. Mean Platelet Volume (MPV) is one of the components of a complete blood routine examination and relatively cheap as a marker in ACS. Determining the sensitivity and specificity of MPV in detecting cases of the acute coronary syndrome, 325 subjects’ medical records were from the period of July 2013 to June 2014; 228 ACS patients met the inclusion criteria. 228 subjects showed a risk factor for age ≥45years of more 195 (85.5%). 122 subjects with hypertension (53.5%) and subjects who smoked 118 (51.8%) that suffered most ACS. Subjects with risk factors for diabetes mellitus, obesity, menopause and dyslipidemia in this study was lower than non-diabetic 161 (70.6%), obese189 (82.9%), nonmenopause 196 (86%) and normal lipid 210 (92.1%). But there was norelation between risk factor with MPV and troponin T statistically. The results of diagnostic tests MPV for the evaluation of patients with ACS, sensitivity 92%, specificity 71%, positive predictive value 95% and negative predictive value 58%.

Knock-in mice harboring a Ca(2+) desensitizing mutation in cardiac troponin C develop early onset dilated cardiomyopathy.

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McConnell, Bradley K; Singh, Sonal; Fan, Qiying; Hernandez, Adriana; Portillo, Jesus P; Reiser, Peter J; Tikunova, Svetlana B

2015-01-01

The physiological consequences of aberrant Ca(2+) binding and exchange with cardiac myofilaments are not clearly understood. In order to examine the effect of decreasing Ca(2+) sensitivity of cTnC on cardiac function, we generated knock-in mice carrying a D73N mutation (not known to be associated with heart disease in human patients) in cTnC. The D73N mutation was engineered into the regulatory N-domain of cTnC in order to reduce Ca(2+) sensitivity of reconstituted thin filaments by increasing the rate of Ca(2+) dissociation. In addition, the D73N mutation drastically blunted the extent of Ca(2+) desensitization of reconstituted thin filaments induced by cTnI pseudo-phosphorylation. Compared to wild-type mice, heterozygous knock-in mice carrying the D73N mutation exhibited a substantially decreased Ca(2+) sensitivity of force development in skinned ventricular trabeculae. Kaplan-Meier survival analysis revealed that median survival time for knock-in mice was 12 weeks. Echocardiographic analysis revealed that knock-in mice exhibited increased left ventricular dimensions with thinner walls. Echocardiographic analysis also revealed that measures of systolic function, such as ejection fraction (EF) and fractional shortening (FS), were dramatically reduced in knock-in mice. In addition, knock-in mice displayed electrophysiological abnormalities, namely prolonged QRS and QT intervals. Furthermore, ventricular myocytes isolated from knock-in mice did not respond to β-adrenergic stimulation. Thus, knock-in mice developed pathological features similar to those observed in human patients with dilated cardiomyopathy (DCM). In conclusion, our results suggest that decreasing Ca(2+) sensitivity of the regulatory N-domain of cTnC is sufficient to trigger the development of DCM.

Beyond triage: the diagnostic accuracy of emergency department nursing staff risk assessment in patients with suspected acute coronary syndromes.

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Carlton, Edward Watts; Khattab, Ahmed; Greaves, Kim

2016-02-01

To establish the accuracy of emergency department (ED) nursing staff risk assessment using an established chest pain risk score alone and when incorporated with presentation high-sensitivity troponin testing as part of an accelerated diagnostic protocol (ADP). Prospective observational study comparing nursing and physician risk assessment using the modified Goldman (m-Goldman) score and a predefined ADP, incorporating presentation high-sensitivity troponin. A UK District ED. Consecutive patients, aged ≥18, with suspected cardiac chest pain and non-ischaemic ECG, for whom the treating physician determined serial troponin testing was required. 30-day major adverse cardiac events (MACE). 960 participants were recruited. 912/960 (95.0%) had m-Goldman scores recorded by physicians and 745/960 (77.6%) by nursing staff. The area under the curve of the m-Goldman score in predicting 30-day MACE was 0.647 (95% CI 0.594 to 0.700) for physicians and 0.572 (95% CI 0.510 to 0.634) for nursing staff (p=0.09). When incorporated into an ADP, sensitivity for the rule-out of MACE was 99.2% (95% CI 94.8% to 100%) and 96.7% (90.3% to 99.2%) for physicians and nurses, respectively. One patient in the physician group (0.3%) and three patients (1.1%) in the nursing group were classified as low risk yet had MACE. There was fair agreement in the identification of low-risk patients (kappa 0.31, 95% CI 0.24 to 0.38). The diagnostic accuracy of ED nursing staff risk assessment is similar to that of ED physicians and interobserver reliability between assessor groups is fair. When incorporating high-sensitivity troponin testing, a nurse-led ADP has a miss rate of 1.1% for MACE at 30 days. Controlled Trials Database (ISRCTN no. 21109279). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Electrospun biocomposite nanofibrous patch for cardiac tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Prabhakaran, Molamma P; Ramakrishna, Seeram [Health Care and Energy Materials Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore); Kai, Dan [NUS Graduate School of Integrative Sciences and Engineering, National University of Singapore (Singapore); Ghasemi-Mobarakeh, Laleh, E-mail: nnimpp@nus.edu.s [Islamic Azad University, Najafabad Branch, Isfahan (Iran, Islamic Republic of)

2011-10-15

A bioengineered construct that matches the chemical, mechanical, biological properties and extracellular matrix morphology of native tissue could be suitable as a cardiac patch for supporting the heart after myocardial infarction. The potential of utilizing a composite nanofibrous scaffold of poly(dl-lactide-co-glycolide)/gelatin (PLGA/Gel) as a biomimetic cardiac patch is studied by culturing a population of cardiomyocyte containing cells on the electrospun scaffolds. The chemical characterization and mechanical properties of the electrospun PLGA and PLGA/Gel nanofibers were studied by Fourier transform infrared spectroscopy, scanning electron microscopy and tensile measurements. The biocompatibility of the scaffolds was also studied and the cardiomyocytes seeded on PLGA/Gel nanofibers were found to express the typical functional cardiac proteins such as alpha-actinin and troponin I, showing the easy integration of cardiomyocytes on PLGA/Gel scaffolds. Our studies strengthen the application of electrospun PLGA/Gel nanofibers as a bio-mechanical support for injured myocardium and as a potential substrate for induction of endogenous cardiomyocyte proliferation, ultimately reducing the cardiac dysfunction and improving cardiac remodeling.

Are There Deleterious Cardiac Effects of Acute and Chronic Endurance Exercise?

Science.gov (United States)

Eijsvogels, Thijs M. H.; Fernandez, Antonio B.; Thompson, Paul D.

2015-01-01

Multiple epidemiological studies document that habitual physical activity reduces the risk of atherosclerotic cardiovascular disease (ASCVD), and most demonstrate progressively lower rates of ASCVD with progressively more physical activity. Few studies have included individuals performing high-intensity, lifelong endurance exercise, however, and recent reports suggest that prodigious amounts of exercise may increase markers for, and even the incidence of, cardiovascular disease. This review examines the evidence that extremes of endurance exercise may increase cardiovascular disease risk by reviewing the causes and incidence of exercise-related cardiac events, and the acute effects of exercise on cardiovascular function, the effect of exercise on cardiac biomarkers, including “myocardial” creatine kinase, cardiac troponins, and cardiac natriuretic peptides. This review also examines the effect of exercise on coronary atherosclerosis and calcification, the frequency of atrial fibrillation in aging athletes, and the possibility that exercise may be deleterious in individuals genetically predisposed to such cardiac abnormalities as long QT syndrome, right ventricular cardiomyopathy, and hypertrophic cardiomyopathy. This review is to our knowledge unique because it addresses all known potentially adverse cardiovascular effects of endurance exercise. The best evidence remains that physical activity and exercise training benefit the population, but it is possible that prolonged exercise and exercise training can adversely affect cardiac function in some individuals. This hypothesis warrants further examination. PMID:26607287

Analysis of troponin I gene polymorphisms and meat quality in ...

African Journals Online (AJOL)

Troponin I is one of myofibrillar proteins required for the calcium regulation of skeletal muscle contraction. The expression of both genes, TNNI1 and TNNI2, in troponin is muscle fibre specific and may affect meat quality traits. In this study, the PCR-RFLP method was applied to genotype 120 Mongcai pigs at three ...

[Cardiac involvement in Churg-Strauss syndrome].

Science.gov (United States)

Brucato, Antonio; Maestroni, Silvia; Masciocco, Gabriella; Ammirati, Enrico; Bonacina, Edgardo; Pedrotti, Patrizia

2015-09-01

Churg-Strauss syndrome, recently renamed eosinophilic granulomatosis with polyangiitis (EGPA), is a rare form of systemic vasculitis, characterized by disseminated necrotizing vasculitis with extravascular granulomas occurring among patients with asthma and tissue eosinophilia. EGPA is classified as a small and medium-sized vessel vasculitis associated with antineutrophil cytoplasmic antibodies (ANCA) and the hypereosinophilic syndrome. Typical clinical features include asthma, sinusitis, transient pulmonary infiltrates and neuropathy. Blood eosinophils are often >1500/µl or more than 10% on the differential leukocyte count. Blood eosinophils should always be tested in unexplained cardiac disorders, and may normalize even after low doses of corticosteroids. ANCA are positive in 40-60% of cases, mainly anti-myeloperoxidase. Heart involvement occurs in approximately 15-60% of EGPA patients, especially those who are ANCA negative. Any cardiac structure can be involved, and patients present with myocarditis, heart failure, pericarditis, arrhythmia, coronary arteritis, valvulopathy, intracavitary cardiac thrombosis. Although cardiovascular involvement is usually an early manifestation, it can also occur later in the course of the disease. A significant proportion of patients with cardiac involvement is asymptomatic. In the absence of symptoms and major ECG abnormalities, cardiac involvement may be detected in nearly 40% of the patients. All patients with EGPA should be studied not only with a detailed history of cardiac symptoms and ECG, but also with echocardiography; if abnormalities are detected, a cardiac magnetic resonance study should be performed. Coronary angiography and endomyocardial biopsy should be reserved to selected cases. Heart involvement carries a poor prognosis and causes 50% of the deaths of these patients. It is often insidious and underestimated. Optimal therapy is therefore important and based on high-dose corticosteroids plus immunosuppressive

N-terminal pro-brain natriuretic peptide for additional risk stratification in patients with non-ST-elevation acute coronary syndrome and an elevated troponin T: an Invasive versus Conservative Treatment in Unstable coronary Syndromes (ICTUS) substudy

NARCIS (Netherlands)

Windhausen, Fons; Hirsch, Alexander; Sanders, Gerard T.; Cornel, Jan Hein; Fischer, Johan; van Straalen, Jan P.; Tijssen, Jan G. P.; Verheugt, Freek W. A.; de Winter, Robbert J.

2007-01-01

BACKGROUND: New evidence has emerged that the assessment of multiple biomarkers such as cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with non-ST-elevation acute coronary syndrome (nSTE-ACS) provides unique prognostic information. The purpose of this

Polymer microfiber meshes facilitate cardiac differentiation of c-kit{sup +} human cardiac stem cells

Energy Technology Data Exchange (ETDEWEB)

Kan, Lijuan [Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA (United States); Thayer, Patrick [Department of Chemical Engineering, School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, VA (United States); Fan, Huimin [Research Institute of Heart Failure, Shanghai East Hospital of Tongji University, Shanghai (China); Ledford, Benjamin; Chen, Miao [Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA (United States); Goldstein, Aaron [Department of Chemical Engineering, School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, VA (United States); Cao, Guohua [School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, VA (United States); He, Jia-Qiang, E-mail: jiahe@vt.edu [Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA (United States)

2016-09-10

Electrospun microfiber meshes have been shown to support the proliferation and differentiation of many types of stem cells, but the phenotypic fate of c-kit{sup +} human cardiac stem cells (hCSCs) have not been explored. To this end, we utilized thin (~5 µm) elastomeric meshes consisting of aligned 1.7 µm diameter poly (ester-urethane urea) microfibers as substrates to examine their effect on hCSC viability, morphology, proliferation, and differentiation relative to cells cultured on tissue culture polystyrene (TCPS). The results showed that cells on microfiber meshes displayed an elongated morphology aligned in the direction of fiber orientation, lower proliferation rates, but increased expressions of genes and proteins majorly associated with cardiomyocyte phenotype. The early (NK2 homeobox 5, Nkx2.5) and late (cardiac troponin I, cTnI) cardiomyocyte genes were significantly increased on meshes (Nkx=2.5 56.2±13.0, cTnl=2.9±0.56,) over TCPS (Nkx2.5=4.2±0.9, cTnl=1.6±0.5, n=9, p<0.05 for both groups) after differentiation. In contrast, expressions of smooth muscle markers, Gata6 and myosin heavy chain (SM-MHC), were decreased on meshes. Immunocytochemical analysis with cardiac antibody exhibited the similar pattern of above cardiac differentiation. We conclude that aligned microfiber meshes are suitable for guiding cardiac differentiation of hCSCs and may facilitate stem cell-based therapies for treatment of cardiac diseases. - Highlights: • First study to characterize c-kit{sup +} human cardiac stem cells on microfiber meshes. • Microfiber meshes seem reducing cell proliferation, but no effect on cell viability. • Microfiber meshes facilitate the elongation of human cardiac stem cells in culture. • Cardiac but not smooth muscle differentiation were enhanced on microfiber meshes. • Microfiber meshes may be used as cardiac patches in cell-based cardiac therapy.

Limited proteolysis combined with isotope labeling and quantitative LC-MALDI MS for monitoring protein conformational changes: a study on calcium-binding sites of cardiac Troponin C

International Nuclear Information System (INIS)

McDonald, Chris; Li Liang

2005-01-01

Studies of protein-protein and protein-ligand interactions are important for understanding biological functions of proteins. A new technique based on the partial proteolysis of proteins combined with quantitative mass spectrometry is developed as a means of tracking structural changes after the formation of a protein-ligand complex. In this technique, a protein of interest with and without the binding of a ligand is digested with an enzyme to generate a set of peptides, followed by separation of the peptides by liquid chromatography. Matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS) is used to identify chromatographically separated peptides, and locate their sequence alignments in the parent protein. Using an isotopically labeled protein as a sample against an unlabeled protein standard, quantitative information can be gathered. This overcomes the inherent lack of quantitative capability of MALDI MS. The utility of the technique to investigate protein-ligand interactions is demonstrated in a model system involving calcium binding to cardiac Troponin C (cTnC). Using this technique, the general location of the three calcium-binding sites of cTnC can be determined by using several different enzymes to generate overlapping peptide maps of cTnC

Innovations in management of cardiac disease: drugs, treatment strategies and technology.

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Foëx, P

2017-12-01

Within the last generation, the management of patients with heart disease has been transformed by advances in drug treatments, interventions and diagnostic technologies. The management of arterial hypertension saw beta-blockers demoted from first- to third-line treatment. Recent studies suggest that the goal of treatment may have to change to lower systolic blood pressures to prevent long-term organ damage. Today less than 15% of coronary revascularizations are surgical and more than 85% are done by interventional cardiologists inserting coronary stents. Thus, managing patients on dual antiplatelet therapy has become an important issue. With new generations of coronary stents, recommendations are changing fast. In the past, decisions concerning non-cardiac surgery after acute myocardial infarction were based on the delay between infarction and non-cardiac surgery. Today, the main concern is the patient's status in respect of dual antiplatelet therapy after primary percutaneous intervention. There have been advances in the management of heart failure but new drugs (ivabradine, sacubitril/valsartan) and cardiac resynchronization are recommended only in patients with an ejection fraction below 35% on optimal medication. Heart failure remains a major perioperative risk factor. Prospective studies have shown that troponin elevations represent myocardial injury (not necessarily myocardial infarction), are mostly silent and are associated with increased 30-day mortality. Monitoring (troponin assays) for myocardial injury in non-cardiac surgery (MINS) seems increasingly justified. The treatment of MINS needs further research. Technological advances, such as intelligent, portable monitors benefit not only patients with cardiac disease but all patients who have undergone major surgery and are on the wards postoperatively. © The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please

Variable effects of high-dose adrenaline relative to standard-dose adrenaline on resuscitation outcomes according to cardiac arrest duration.

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Jeung, Kyung Woon; Ryu, Hyun Ho; Song, Kyung Hwan; Lee, Byung Kook; Lee, Hyoung Youn; Heo, Tag; Min, Yong Il

2011-07-01

Adjustment of adrenaline (epinephrine) dosage according to cardiac arrest (CA) duration, rather than administering the same dose, may theoretically improve resuscitation outcomes. We evaluated variable effects of high-dose adrenaline (HDA) relative to standard-dose adrenaline (SDA) on resuscitation outcomes according to CA duration. Twenty-eight male domestic pigs were randomised to the following 4 groups according to the dosage of adrenaline (SDA 0.02 mg/kg vs. HDA 0.2mg/kg) and duration of CA before beginning cardiopulmonary resuscitation (CPR): 6 min SDA, 6 min HDA, 13 min SDA, or 13 min HDA. After the predetermined duration of untreated ventricular fibrillation, CPR was provided. All animals in the 6 min SDA, 6 min HDA, and 13 min HDA groups were successfully resuscitated, while only 4 of 7 pigs in the 13 min SDA group were successfully resuscitated (p=0.043). HDA groups showed higher right atrial pressure, more frequent ventricular ectopic beats, higher blood glucose, higher troponin-I, and more severe metabolic acidosis than SDA groups. Animals of 13 min groups showed more severe metabolic acidosis and higher troponin-I than animals of 6 min groups. All successfully resuscitated animals, except two animals in the 13 min HDA group, survived for 7 days (p=0.121). Neurologic deficit score was not affected by the dose of adrenaline. HDA showed benefit in achieving restoration of spontaneous circulation in 13 min CA, when compared with 6 min CA. However, this benefit did not translate into improved long-term survival or neurologic outcome. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Exercise tolerance in asymptomatic patients with moderate-severe valvular heart disease and preserved ejection fraction.

Science.gov (United States)

Olaf, Schulz; Debora, Brala; Ricarda, Bensch; Gunnar, Berghöfer; Jochen, Krämer; Schimke, Ingolf; Halle, Martin; Jaffe, Allan

2012-12-20

For asymptomatic patients with moderate-severe valvular heart disease, in whom symptoms may be obscured, objective exercise tolerance measures are warranted for decisions concerning physical activities and surgical treatment. We compared 61 patients (39 with aortic stenosis, 22 with aortic or mitral regurgitation) to 23 controls without valvular heart disease but with indications for stress testing. All participants underwent cardiopulmonary function testing and dobutamine stress echocardiography. Blood was drawn before as well as after bicycle stress to assess high-sensitivity cardiac troponin T (hscTnT). Patients who underwent surgery were re-evaluated 1.5 ±0.9 years after the operation. Conventional bicycle test following guideline criteria revealed a pathologic result in 26% of the patients, whereas spiroergometry showed an objectively reduced exercise tolerance in 59%, reaching a prognostically relevant feature in 39%. Stress echocardiography detected a reduced systolic reserve in 33% and elevated filling pressures in 62%. These abnormalities were significantly less present in the control group (4, 17, 9, 9, 4% respectively, p valvular heart disease beyond stress-test criteria recommended in recent guidelines. High-sensitivity cardiac troponin I may be of additional value. Results of these tests presage post-operative function.

UCP3 Ablation Exacerbates High-Salt Induced Cardiac Hypertrophy and Cardiac Dysfunction

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Hongmei Lang

2018-04-01

Full Text Available Background/Aims: Excessive salt intake and left ventricular hypertrophy (LVH are both critical for the development of hypertension and heart failure. The uncoupling protein 3 (UCP3 plays a cardio-protective role in early heart failure development. However, the potential role for UCP3 in salt intake and LVH is unclear. Methods: UCP3-/- and C57BL/6 mice were placed on either a normal-salt (NS, 0.5% or a high-salt (HS, 8% diet for 24 weeks. The cardiac function, endurance capacity, energy expenditure, and mitochondrial functional capacity were measured in each group. Results: Elevated blood pressure was only observed in HS-fed UCP3-/- mice. High salt induced cardiac hypertrophy and dysfunction were observed in both C57BL/6 and UCP3-/- mice. However, the cardiac lesions were more profound in HS-fed UCP3-/- mice. Furthermore, HS-fed UCP3-/-mice experienced more severe mitochondrial respiratory dysfunction compared with HS-fed C57BL/6 mice, represented by the decreased volume of oxygen consumption and heat production at the whole-body level. Conclusion: UCP3 protein was involved in the incidence of high-salt induced hypertension and the progression of cardiac dysfunction in the early stages of heart failure. UCP3 ablation exacerbated high-salt-induced cardiac hypertrophy and cardiac dysfunction.

Troponin-positive chest pain with unobstructed coronary arteries: incremental diagnostic value of cardiovascular magnetic resonance imaging.

Science.gov (United States)

Pathik, Bhupesh; Raman, Betty; Mohd Amin, Nor Hanim; Mahadavan, Devan; Rajendran, Sharmalar; McGavigan, Andrew D; Grover, Suchi; Smith, Emma; Mazhar, Jawad; Bridgman, Cameron; Ganesan, Anand N; Selvanayagam, Joseph B

2016-10-01

Troponin-positive chest pain patients with unobstructed coronaries represent a clinical dilemma. Cardiovascular magnetic resonance (CMR) imaging has an increasingly prominent role in the assessment of these patients; however, its utility in addition to expert clinical judgement is unclear. We sought to determine the incremental diagnostic value of CMR and the heterogeneity in diagnoses by experienced cardiologists when presented with blinded clinical and investigative data in this population. A total of 125 consecutive patients presenting to a tertiary centre between 2010 and 2014 with cardiac chest pain, elevated troponin (>29 ng/L), and unobstructed coronaries were enrolled and underwent CMR. A panel of three experienced cardiologists unaware of the CMR diagnosis and blinded to each other's assessment provided a diagnosis based on clinical and investigative findings. A consensus panel diagnosis was defined as two or more cardiologists sharing the same clinical diagnosis. Findings were classified into acute myocarditis, Takotsubo cardiomyopathy, acute myocardial infarction (AMI), or indeterminate. CMR provided a diagnosis in 87% of patients. Consensus panel diagnosis and CMR were concordant in 65/125 (52%) patients. There was an only moderate level of agreement between the three cardiologists (k = 0.47, P < 0.05) and a poor level of agreement between the consensus panel and CMR (k = 0.38, P < 0.05) with the most disagreement seen in patients with AMI diagnosed on CMR. The clinical diagnosis of patients with non-obstructive coronaries and positive troponin remains a challenge. The concordance between CMR and clinical diagnosis is poor. CMR provides a diagnosis in majority of these patients. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

[The role of biochemical markers of myocardial damage in clinical practice: the diagnosis of infarct and risk stratification. The Intersociety Interdisciplinary Study Group of the ANMCO-SIBioC-SIMeL, Markers of Muocardial Lesions. L'Associazione Nazionale Medici Cardiologi Ospedalieri-Società Italiana di Biochimica Clinica-Società Italiana di Medicina di Laboratorio].

Science.gov (United States)

Ottani, F; Galvani, M; Panteghini, M; Dolci, A; Plebani, M; Tubaro, M; Zaninotto, M

2000-01-01

For many years creatine kinase (CK) and CK-MB isoenzymes were used together with the ECG to confirm the presence of myocardial infarction. During the last decade newer cardiac markers have been introduced and immunological test systems developed for their quantification. Among these new markers, a prominent role has emerged for cardiac troponins (T or I). These technological advanced assays have shown greater sensitivity compared to "conventional cardiac enzymes;, thereby identifying patients with small--at times, microscopic--infarcts who would not have met defining criteria for myocardial infarction in an earlier era. Another major advantage shown by both cardiac troponins with respect to "conventional cardiac enzymes" is their ability to predict clinical outcome over a short- or long-term follow-up in patients with acute coronary syndromes, and this appears to be particularly relevant in patients with micronecrosis, who constitute a high-risk subgroup of unstable angina patients. Recently, myoglobin has also been widely applied as a marker. Although lacking in myocardial specificity, it is the earliest marker to show an increase after coronary occlusion. Thus, the combined use of myoglobin and a cardiospecific structural protein such as troponin T or I may prove an attractive strategy for biochemical testing in chest pain patients. With the routine use of these novel cardiac markers, fascinating opportunities are now open in the field of diagnostic classification (making the World Health Organization definition of myocardial infarction obsolete) and risk stratification in chest pain patients; opportunities that were unforeseen in the era of cardiac enzymes. However, the use of these markers has also posed some important questions on: a) the best and most cost-effective diagnostic strategy in chest pain patients; b) the remaining role of cardiac enzymes; c) the therapeutic consequences of a positive test result.

Replacement of Cetyltrimethylammoniumbromide Bilayer on Gold Nanorod by Alkanethiol Crosslinker for Enhanced Plasmon Resonance Sensitivity

Science.gov (United States)

Casas, Justin; Venkataramasubramani, Meenakshi; Wang, Yanyan; Tang, Liang

2013-01-01

Surface modification of gold nanorods (GNRs) is often problematic due to tightly packed cetyltrimethylammoniumbromide (CTAB) bilayer. Herein, we performed a double phase transfer ligand exchange to achieve displacement of CTAB on nanorods. During the removal, 11-mercaptoundecanoic acid (MUDA) crosslinker is simultaneously assembled on nanorod surfaces to prevent aggregation. The resulting MUDA-GNRs retain the shape and position of plasmon peaks similar to CTAB-capped GNRs. The introduction of carboxyl groups allows covalent conjugation of biological receptors in a facile fashion to construct a robust, label-free biosensor based on localized surface plasmon resonance (LSPR) transduction of biomolecular interaction. More importantly, smaller MUDA layer on the GNRs reduces the distance of target binding to the plasmonic nanostructure interface, leading to a significant enhancement in LSPR assay sensitivity and specificity. Compared to modification using conventional electropolymer adsorption, MUDA-coated gold nanosensor exhibits five times lower detection limit for cardiac troponin I assay with a high selectivity. PMID:23816849

Reversible Stress Cardiomyopathy Presenting as Acute Coronary Syndrome with Elevated Troponin in the Absence of Regional Wall Motion Abnormalities: A Forme Fruste of Stress Cardiomyopathy?

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Mahesh Anantha Narayanan

2014-01-01

Full Text Available We present a case of reversible stress cardiomyopathy in a surgical patient, described here as a forme fruste due to its atypical features. It is important to recognize such unusual presentation of stress cardiomyopathy that mimics acute coronary syndrome. Stress cardiomyopathy commonly presents as acute coronary syndrome and is characterized by typical or atypical variants of regional wall motion abnormalities. We report a 60-year-old Caucasian male with reversible stress cardiomyopathy following a sternal fracture fixation. Although the patient had several typical features of stress cardiomyopathy including physical stress, ST-segment elevation, elevated cardiac biomarkers and normal epicardial coronaries, there were few features that were atypical, including unusual age, gender, absence of regional wall motion abnormalities, high lateral ST elevation, and high troponin-ejection fraction product. In conclusion, this could represent a forme fruste of stress cardiomyopathy.

High-sensitivity cardiac troponin T is associated with cognitive decline in older adults at high cardiovascular risk

DEFF Research Database (Denmark)

Wijsman, Liselotte W; de Craen, Anton JM; Trompet, Stella

2016-01-01

(mean baseline score (standard error (SE)) lowest vs highest third 65.91 (1.16) vs 69.40 (1.10) seconds, p vs 22.40 (0.31) digits coded, p Picture-Word Learning test (9.45 (0.09) vs 9.31 (0.08) pictures remembered, p = 0.......002) and delayed Picture-Word Learning test (10.33 (0.12) vs 10.10 (0.12) pictures remembered, p = 0.013). Furthermore, participants with higher hs-cTnT had steeper decline on Stroop test (mean annual change (SE) lowest vs highest third 0.34 (0.12) vs 1.06 (0.12) seconds, p = 0.013), Letter-Digit Coding test (-0.......29 (0.03) vs -0.46 (0.03) digits coded, p Picture-Word Learning test (0.01 (0.01) vs -0.06 (0.01) pictures remembered, p Picture-Word Learning test (-0.03 (0.01) vs -0.12 (0.02) pictures remembered, p = 0.001). Associations were independent of cardiovascular...

Sensitivity of scintigraphy with 111In-lymphocytes for detection of cardiac allograft rejection

International Nuclear Information System (INIS)

Eisenberg, S.B.; Eisen, H.J.; Sobel, B.E.; Bergmann, S.R.; Bolman, R.M. III

1988-01-01

We recently demonstrated the feasibility of noninvasive detection of cardiac allograft rejection after administration of indium-111-labeled lymphocytes. To determine the sensitivity and specificity of the technique, as well as its value for delineating the severity of rejection, we studied 16 dogs with heterotopic thoracic cardiac allografts. Five animals were evaluated while exposed to immunosuppressive agents. Animals were scanned sequentially after administration of 100-400 microCi of indium-111-labeled autologous lymphocytes. Myocardial lymphocyte infiltration was expressed as the indium excess (IE), defined as the ratio of indium activity of the transplant or native heart compared with that in blood. Scintigraphic results were compared with characteristics of simultaneously obtained endomyocardial biopsies. Among 17 biopsy documented episodes of rejection, 16 were detected scintigraphically. Among 18 biopsies with no evidence of rejection, scintigraphy was uniformly negative. Thus, the sensitivity and specificity of scintigraphy were 94 and 100%, respectively. Biopsies graded as showing no rejection were associated with an IE of 0.3 +/- 0.5 (+/- SD); those graded as mild, 2.8 +/- 1.7; those as moderate, 10.7 +/- 7.2; and those graded as indicative of severe rejection, 14.2 +/- 4.5. Thus, scintigraphy with indium-111-labeled lymphocytes sensitively and specifically detects cardiac allograft rejection and delineates the intensity of the rejection process. It should be useful clinically for assessing potential allograft rejection noninvasively

Association between cardiac biomarkers and the development of ESRD in patients with type 2 diabetes mellitus, anemia, and CKD

DEFF Research Database (Denmark)

Desai, Akshay S; Toto, Robert; Jarolim, Petr

2011-01-01

In patients with chronic kidney disease (CKD), as in other populations, elevations in cardiac biomarker levels predict increased risk of cardiovascular events. We examined the value of troponin T (TnT) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in assessing the risk of developing e...

Routine Troponin Measurements Are Unnecessary to Exclude Asymptomatic Coronary Events in Acute Ischemic Stroke Patients.

Science.gov (United States)

Ali, Farwa; Young, Jimmy; Rabinstein, Alejandro A; Flemming, Kelly D; Fugate, Jennifer E

2016-05-01

Obtaining serum troponin levels in every patient with acute stroke is recommended in recent stroke guidelines, but there is no evidence that these contribute positively to clinical care. We sought to determine the clinical significance of measuring troponin levels in acute ischemic stroke patients. We reviewed 398 consecutive patients with acute ischemic stroke at a large academic institution from 2010 to 2012. Troponin levels were measured as a result of protocol in place during part of the study period. The mean age was 70 years (standard deviation ±16 years) and 197 (49.5%) were men. Chronic kidney disease was present in 78 (19.6%), coronary artery disease in 107 (26.9%), and atrial fibrillation in 107 (26.9%). Serum troponin T was measured in 246 of 398 patients (61.8%). Troponin was elevated (>.01 ng/mL) at any point in 38 of 246 patients (15.5%) and was elevated in 28 patients at all 3 measurements (11.3% of those with troponin measured). Only 4 of 246 patients (1.6%) had a significant uptrend. Two were iatrogenic in the setting of hemodynamic augmentation using vasopressors to maintain cerebral perfusion. One case was attributed to stroke and chronic kidney disease and another case to heart failure from inflammatory fibrocalcific mitral valvular heart disease. Serum troponin elevation in patients with ischemic stroke is not usually caused by clinically significant acute myocardial ischemia unless iatrogenic in the setting of vasopressor administration. Serum troponin levels should be measured judicially, based on clinical context, rather than routinely in all stroke patients. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

The profound effects of microcystin on cardiac antioxidant enzymes, mitochondrial function and cardiac toxicity in rat

International Nuclear Information System (INIS)

Qiu Tong; Xie Ping; Liu Ying; Li Guangyu; Xiong Qian; Hao Le; Li Huiying

2009-01-01

Deaths from microcystin toxication have widely been attributed to hypovolemic shock due to hepatic interstitial hemorrhage, while some recent studies suggest that cardiogenic complication is also involved. So far, information on cardiotoxic effects of MC has been rare and the underlying mechanism is still puzzling. The present study examined toxic effects of microcystins on heart muscle of rats intravenously injected with extracted MC at two doses, 0.16LD 50 (14 μg MC-LReq kg -1 body weight) and 1LD 50 (87 μg MC-LReq kg -1 body weight). In the dead rats, both TTC staining and maximum elevations of troponin I levels confirmed myocardial infarction after MC exposure, besides a serious interstitial hemorrhage in liver. In the 1LD 50 dose group, the coincident falls in heart rate and blood pressure were related to mitochondria dysfunction in heart, while increases in creatine kinase and troponin I levels indicated cardiac cell injury. The corresponding pathological alterations were mainly characterized as loss of adherence between cardiac myocytes and swollen or ruptured mitochondria at the ultrastructural level. MC administration at a dose of 1LD 50 not only enhanced activities and up-regulated mRNA transcription levels of antioxidant enzymes, but also increased GSH content. At both doses, level of lipid peroxides increased obviously, suggesting serious oxidative stress in mitochondria. Simultaneously, complex I and III were significantly inhibited, indicating blocks in electron flow along the mitochondrial respiratory chain in heart. In conclusion, the findings of this study implicate a role for MC-induced cardiotoxicity as a potential factor that should be considered when evaluating the mechanisms of death associated with microcystin intoxication in Brazil

The diagnosis of anthracycline-induced cardiac damage and heart failure

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Jarosław Dudka

2009-05-01

Full Text Available Routine examinations during chemotherapy containing anthracyclines evaluate heart function before treatment and monitor cardiotoxic effects during and after therapy. A number of methods are useful in cardiac assessment, including electrocardiography, radiology techniques (RTG, CT, MRI, PET-CT, PET-MRI, echocardiography, radioisotope imaging techniques (scyntygraphy, MUGA, PET, and ultra-structure evaluation in biopsy samples. Nevertheless, there is a continuous need for new methods to predict future damage at the initial stages of cardiac changes. In recent years the therapeutic usefulness of biochemical blood parameters in anthracycline-treated patients has been assessed. The levels of cardiac troponines (cTnI, cTnT, natriuretic peptides (ANP, BNP, and endothelin 1 have been included in the studies. Heart-type fatty acid binding protein (H-FABP is another promising factor showing cardiomyocytic impairment. However, the clinical use of biochemical parameters in diagnosing anthracycline-related cardiotoxicity is still a controversial issue.

Mild troponin I elevation does not predict ischemia on myocardial perfusion imaging

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Le Dung Ha

2017-08-01

Full Text Available IntroductionData are limited on the degree of mild troponin I elevation and clinical risk factors in predicting myocardial ischemia.MethodsHospitalized adult patients who underwent myocardial perfusion imaging (MPI from 2015 to 2016 at Rochester General Hospital and had mild troponin I elevation (>0.1 and <1.5 ng/mL were included. Predictors of outcomes were determined using logistic regression model.ResultsOne hundred and sixty-six patients with mild troponin I elevation who underwent MPI were followed. Mean age was 69.6 ± 12.5 years and 53.0% of the patients were female. Fourteen patients (8.4% presented with typical chest pain (CP, 60 patients (36.1% had atypical CP and 92 patients (55.4% had no CP on presentation. MPI was positive for ischemia in 45 patients (27.1%. There was no difference in peak troponin I level with ischemia versus no ischemia on MPI (0.34 ng/dL [0.13-0.69] vs. 0.23 ng/dL [0.14-0.50], p value 0.254. Atypical CP did not predict the presence of ischemia on MPI (odds ratio [OR] 1.97, 95% confidence interval [CI] 0.91-4.26. Coronary artery disease (CAD history (age and sex adjusted p value 0.013, diabetes (adjusted p value 0.036, creatinine ≥2 mg/dL (adjusted p value 0.019 and dialysis (adjusted p value 0.006 were statistically significant predictors of ischemia on MPI.ConclusionsIn patients presenting with mild troponin I elevation, peak troponin I level did not predict ischemia on MPI. The presence of CAD history, diabetes, elevated creatinine and dialysis were predictors of ischemia on MPI.

Combinatorial therapy of exercise-preconditioning and nanocurcumin formulation supplementation improves cardiac adaptation under hypobaric hypoxia.

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Nehra, Sarita; Bhardwaj, Varun; Bansal, Anju; Saraswat, Deepika

2017-09-26

Chronic hypobaric hypoxia (cHH) mediated cardiac insufficiencies are associated with pathological damage. Sustained redox stress and work load are major causative agents of cardiac insufficiencies under cHH. Despite the advancements made in pharmacological (anti-oxidants, vasodilators) and non-pharmacological therapeutics (acclimatization strategies and schedules), only partial success has been achieved in improving cardiac acclimatization to cHH. This necessitates the need for potent combinatorial therapies to improve cardiac acclimatization at high altitudes. We hypothesize that a combinatorial therapy comprising preconditioning to mild aerobic treadmill exercise and supplementation with nanocurcumin formulation (NCF) consisting of nanocurcumin (NC) and pyrroloquinoline quinone (PQQ) might improve cardiac adaptation at high altitudes. Adult Sprague-Dawley rats pre-conditioned to treadmill exercise and supplemented with NCF were exposed to cHH (7620 m altitude corresponding to pO2~8% at 28±2°C, relative humidity 55%±1%) for 3 weeks. The rat hearts were analyzed for changes in markers of oxidative stress (free radical leakage, lipid peroxidation, manganese-superoxide dismutase [MnSOD] activity), cardiac injury (circulating cardiac troponin I [TnI] and T [cTnT], myocardial creatine kinase [CK-MB]), metabolic damage (lactate dehydrogenase [LDH] and acetyl-coenzyme A levels, lactate and pyruvate levels) and bio-energetic insufficiency (ATP, p-AMPKα). Significant modulations (p≤0.05) in cardiac redox status, metabolic damage, cardiac injury and bio-energetics were observed in rats receiving both NCF supplementation and treadmill exercise-preconditioning compared with rats receiving only one of the treatments. The combinatorial therapeutic strategy showed a tremendous improvement in cardiac acclimatization to cHH compared to either exercise-preconditioning or NCF supplementation alone which was evident from the effective modulation in redox, metabolic, contractile

5 A study analysing the diagnostic performance of ECG interpretation for 30-day major cardiac events in the emergency department.

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Morris, Niall; Body, Rick

2017-12-01

This study evaluates the diagnostic accuracy of an Emergency Medicine (EM) clinician at identifying ischaemia on an ECG using 30-day major adverse cardiac events (MACE) as the primary outcome. This is a secondary analysis of a prospective, multi-centre, observational cohort at 14 centres: the Bedside Evaluation of Sensitive Troponin study. All fourteen Emergency Departments were based in the United Kingdom. Emergency physicians' assessments of the ECG were collected using a standardised form. Clinicians were asked to judge whether the ECG demonstrated ischaemia, the presence of ST depression (STD) and if there was abnormal T wave inversion (ATWI). Patients provided written informed consent and underwent serial high sensitivity troponin testing. 30 day follow-up was performed by research nurses using a standardised form via telephone. The primary outcome was 30-day major adverse cardiac events, defined as acute myocardial infarction, any cause of death and coronary revascularisation. In total, 756 patients were included in the analysis. Clinicians' ECG diagnosis of ischaemia for 30-day MACE: ECG ischaemia produces a sensitivity (Sn) of 19.54% (95% CI:11.81% to 29.43%), specificity (Sp) of 93.27% (95% CI:91.10% to 95.05%), positive predictive value (PPV) of 27.42% (95% CI:18.47% to 38.65%) and negative predictive value (NPV) of 89.91% (95%CI 88.92% to 90.83%). ECG ST depression produces Sn of 16.09% (9.09% to 25.52%), Sp of 89.69% (87.13% to 91.89%), PPV 16.87 (10.68% to 25.62%), and NPV 89.15% (88.19% to 90.04%). ECG ATWI produces Sn of 4.60% (1.27% to 11.36%), Sp of 91.63% (89.27% to 93.62%), PPV of 6.67% (2.59% to 16.12%) and NPV of 88.07% (87.52% to 88.6). This is the first prospective, multi-centre cohort study, that assess the diagnostic performance of EM clinician's ECG interpretation, with 30-day MACE as the primary outcome. The findings are highly relevant to EM as they represent the ECG terms used by popular acute coronary syndrome clinical decision rules

Duration of Untreated Cardiac Arrest and Clinical Relevance of Animal Experiments: The Relationship Between the "No-Flow" Duration and the Severity of Post-Cardiac Arrest Syndrome in a Porcine Model.

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Babini, Giovanni; Grassi, Luigi; Russo, Ilaria; Novelli, Deborah; Boccardo, Antonio; Luciani, Anita; Fumagalli, Francesca; Staszewsky, Lidia; Fiordaliso, Fabio; De Maglie, Marcella; Salio, Monica; Zani, Davide D; Letizia, Teresa; Masson, Serge; Luini, Mario V; Pravettoni, Davide; Scanziani, Eugenio; Latini, Roberto; Ristagno, Giuseppe

2018-02-01

The study investigated the effect of untreated cardiac arrest (CA), that is, "no-flow" time, on postresuscitation myocardial and neurological injury, and survival in a pig model to identify an optimal duration that adequately reflects the most frequent clinical scenario. An established model of myocardial infarction followed by CA and cardiopulmonary resuscitation was used. Twenty-two pigs were subjected to three no-flow durations: short (8-10 min), intermediate (12-13 min), and long (14-15 min). Left ventricular ejection fraction (LVEF) was assessed together with thermodilution cardiac output (CO) and high sensitivity cardiac troponin T (hs-cTnT). Neurological impairment was evaluated by neurological scores, serum neuron specific enolase (NSE), and histopathology. More than 60% of animals survived when the duration of CA was ≤13 min, compared to only 20% for a duration ≥14 min. Neuronal degeneration and neurological scores showed a trend toward a worse recovery for longer no-flow durations. No animals achieved a good neurological recovery for a no-flow ≥14 min, in comparison to a 56% for a duration ≤13 min (P = 0.043). Serum NSE levels significantly correlated with the no-flow duration (r = 0.892). Longer durations of CA were characterized by lower LVEF and CO compared to shorter durations (P flow time, the higher was the number of defibrillations delivered (P = 0.043). The defibrillations delivered significantly correlated with LVEF and plasma hs-cTnT. Longer no-flow durations caused greater postresuscitation myocardial and neurological dysfunction and reduced survival. An untreated CA of 12-13 min may be an optimal choice for a clinically relevant model.

Evaluation of acute cardiac and chest wall damage after shocks with a subcutaneous implantable cardioverter-defibrillator in swine

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KILLINGSWORTH, CHERYL R.; MELNICK, SHARON B.; LITOVSKY, SILVIO H.; IDEKER, RAYMOND E.; WALCOTT, GREGORY P.

2013-01-01

Background A subcutaneous implantable cardioverter defibrillator (S-ICD) could ease placement and reduce complications of transvenous ICDs, but requires more energy than transvenous ICDs. Therefore we assessed cardiac and chest wall damage caused by the maximum energy shocks delivered by both types of clinical devices. Methods During sinus rhythm, anesthetized pigs (38±6 kg) received an S-ICD (n = 4) and five 80-Joule (J) shocks, or a transvenous ICD (control, n = 4) and five 35-J shocks. An inactive S-ICD electrode was implanted into the same control pigs to study implant trauma. All animals survived 24-hours. Troponin I and creatine kinase muscle isoenzyme (CK-MM) were measured as indicators of myocardial and skeletal muscle injury. Histopathological injury of heart, lungs, and chest wall was assessed using semi-quantitative scoring. Results Troponin I was significantly elevated at 4- and 24-hours (22.6±16.3 and 3.1±1.3 ng/ml; baseline 0.07±0.09 ng/ml) in control pigs but not in S-ICD pigs (0.12±0.11 and 0.13±0.13 ng/ml; baseline 0.06±0.03 ng/ml). CK-MM was significantly elevated in S-ICD pigs after shocks (6544±1496 and 9705±6240 U/L; baseline 704±398 U/L) but not in controls. ECG changes occurred post-shock in controls but not in S-ICD pigs. The myocardium and lungs were histologically normal in both groups. Subcutaneous injury was greater in S-ICD compared to controls. Conclusion Although CK-MM suggested more skeletal muscle injury in S-ICD pigs, significant cardiac, lung, and chest wall histopathological changes were not detected in either group. Troponin I data indicate significantly less cardiac injury from 80-J S-ICD shocks than 35-J transvenous shocks. PMID:23713608

Point of Care Cardiac Troponin Assay Analytical Performances for their Use in Clinical Routine.

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Dupuy, Anne M; Baillet, Solenne; Dumont, Richard; Giraud, Isabelle; Badiou, Stephanie; Bargnoux, Anne S; Kuster, Nils; Roubille, Francois; Cristol, Jean Paul

2017-04-01

We report the analytical and clinical performances of the Alere Triage Cardiac3© Panel on the Triage MeterPro© instrument, comparing concordance with hs-cTnT results from central laboratory above the respective 99th percentiles and determining the clinical sensitivity within the framework of AMI. The concordance was obtained with these two methods among unselected patients admitted to both the emergency and cardiology departments. The LoD of the assay is 0.010 µg/L. At 99th percentile (0.02 µg/L) the CV was found to be 18%, below the clinically acceptable cutoff of 20%. In the overall population, ROC AUC was not significantly different between the central laboratory assay and POC assay, with 0.952 (95% CI, 0.918 - 0.952) for hs-cTnT concentrations at presentation and 0.953 (95% CI, 0.912 - 0.953) for cTnI. Sensitivity and specificity of hs-cTnT vs. cTnI for AMI (n = 32) were 97% and 78% vs. 91% and 86%, respectively. Our results indicated 90.4% concordance between the two methods using the 99th percentile specific for each assay. The Kappa coefficient was higher than 0.75, and the strength of agreement could be considered to be good. The results of cTnI Alere assays provide similar clinical classification of patients, particularly for the AMI group as compared to the central laboratory hs-cTnT assay and could be suitable for clinical in accordance with the recommendations of Global Task Force guidelines.

Cardiac effects of granisetron in a prospective crossover randomized dose comparison trial.

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Cakir, F B; Yapar, O; Canpolat, C; Akalin, F; Berrak, S G

2012-10-01

Cardiac side effects of granisetron have been studied mostly in adult patients that are using cardiotoxic chemotherapeutics. There is limited evidence in pediatric age group and no information in pediatric oncology patients with non-cardiotoxic chemotherapeutics. In this prospective, crossover randomized study, the cardiac side effects of granisetron are compared in pediatric oncology patients who had carboplatin based chemotherapy. They were randomized to receive either 10 or 40 μg kg(-1) dose(-1) of granisetron before each cycle of chemotherapy. We drew blood for creatine phosphokinase (CPK), CPK-muscle band (MB) and Troponin-T before and 24 h after administering granisetron. Electrocardiography (ECG) tracings were taken at 0, 1, 2, 3, 6 and 24 h of granisetron. Twenty-four hours Holter ECG monitorisation was performed after each granisetron infusion. A total of 16 patients (median 8.7 years of age) were treated with weekly consecutive courses of carboplatin. There was bradycardia (p = 0.000) in patients that had granisetron at 40 μg/kg and PR interval was shortened in patients that had granisetron at 10 μg/kg dose (p = 0.021). At both doses of granisetron, QTc interval and dispersion were found to be similar. CPK, CK-MB and Troponin-T values were found to be normal before and 24 h after granisetron infusion. As the first study that has studied cardiac side effects of granisetron in patients that are not using cardiotoxic chemotherapeutics, we conclude that granisetron at 40 μg kg(-1) dose(-1) causes bradycardia only. We have also demonstrated that granisetron does not cause any clinically cardiac side effects either at 10 or 40 μg kg(-1) dose(-1). However, our results should be supported by prospective randomized studies with larger samples of patient groups.

Incidencia de eventos vasculares mayores después de cirugía no cardiaca: impacto del monitoreo perioperatorio con troponina y electrocardiograma Incidence of major vascular events after cardiac surgery: impact of preoperative monitoring with troponin and electrocardiogram

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Sandra M Quiroga

2009-06-01

led to an increased risk of major vascular events among patients undergoing non-cardiac surgery. Troponin and electrocardiogram monitoring would further identify these major vascular events. Methods: we prospectively collected data on elegible patients (non-selected individuals aged 45 or older undergoing non-cardiac surgery under general or regional anesthesia in two hospitals in Bucaramanga, with expected length of stay longer than 24 hours during a time-interrupted series, before and after postoperative diagnostic monitoring (blinded assessment of troponin T and electrocardiograms ignoring clinical data. For the period before the intervention (usual clinical care, two independent reviewers extracted clinical information from clinical histories (of all eligible patients from 3 randomly-selected months of 2005. For the period after diagnostic monitoring, we followed 100 consecutive eligible patients. Primary outcome was a composite of major vascular events within hospital, including myocardial infarction (defined as any troponin elevation associated with electrocardiographic changes suggesting ischemia, regardless of symptoms. Results: we included 534 clinical charts and 100 prospective surgical patients (mean age 62.2, SD 12.9 years; 56% women. The more frequent surgical procedures were orthopedics (26.8% followed by abdominal (20.2%. The incidence of major vascular events recorded in clinical charts was 2.8%, compared with 7% among monitored patients (p=0,071. All four myocardial infarctions identified among the later group were silent. Conclusion: postoperative monitoring with troponin and electrocardiography identified a higher proportion of major vascular events, mainly silent myocardial infarctions.

Correlation of cardiac Troponin I levels (10 folds upper limit of normal) and extent of coronary artery disease in Non-ST elevation myocardial infarction

International Nuclear Information System (INIS)

Qadir, F.; Khan, M.; Hanif, B.; Lakhani, S.L.; Farooq, S.

2010-01-01

Objective: To determine the correlation of cardiac troponin I (cTnI) 10 folds upper limit of normal (ULN) and extent of coronary artery disease (CAD) in Non-ST-elevation myocardial infarction (NSTEMI). Methods: A cross-sectional study was conducted on 230 consecutive NSTEMI patients admitted in Tabba Heart Institute, Karachi between April to December 2008. cTnI was measured using MEIA method. All patients underwent coronary angiography in the index hospitalization. Stenosis > 70% in any of the three major epicardial vessels was considered significant CAD. Extent of CAD was defined as significant single, two or three vessel CAD. Chi-square test was applied to test the association between cTnI levels and CAD extent. Results: Out of 230 patients, in 111 patients with cTnI levels 10 folds ULN, 23(19.3%) had single vessel, 37(31.1 %) had two vessel and 55(46.2%) had three vessel significant CAD. The results suggest that there was an insignificant association between the cTnI levels and single vessel, two vessel and the overall CAD extent (p= 0.35, p= 0.21 and p= 0.13 respectively), however there was a statistically significant association between the cTnI levels and three vessel CAD (p < 0.04). Conclusion: Higher cTnI levels are associated with an increased proportion of severe three vessel CAD involvement. Prompt identification and referral of this patient subset to early revascularization strategies would improve clinical outcomes. (author)

Calcium-binding properties of troponin C in detergent-skinned heart muscle fibers

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Pan, B.S.; Solaro, R.J.

1987-01-01

In order to obtain information with regard to behavior of the Ca 2+ receptor, troponin C (TnC), in intact myofilament lattice of cardiac muscle, we investigated Ca 2+ -binding properties of canine ventricular muscle fibers skinned with Triton X-100. Analysis of equilibrium Ca 2+ -binding data of the skinned fibers in ATP-free solutions suggested that there were two distinct classes of binding sites which were saturated over the physiological range of negative logarithm of free calcium concentration (pCa): class I (KCa = 7.4 X 10(7) M-1, KMg = 0.9 X 10(3) M-1) and class II (KCa = 1.2 X 10(6) M-1, KMg = 1.1 X 10(2) M-1). The class I and II were considered equivalent, respectively, to the Ca 2+ -Mg 2+ and Ca 2+ -specific sites of TnC. The assignments were supported by TnC content of the skinned fibers determined by electrophoresis and 45 Ca autoradiograph of electroblotted fiber proteins. Dissociation of rigor complexes by ATP caused a downward shift of the binding curve between pCa 7 and 5, an effect which could be largely accounted for by lowering of KCa of the class II sites. When Ca 2+ binding and isometric force were measured simultaneously, it was found that the threshold pCa for activation corresponds to the range of pCa where class II sites started to bind Ca 2+ significantly. We concluded that the low affinity site of cardiac TnC plays a key role in Ca 2+ regulation of contraction under physiological conditions, just as it does in the regulation of actomyosin ATPase. Study of kinetics of 45 Ca washout from skinned fibers and myofibrils revealed that cardiac TnC in myofibrils contains Ca 2+ -binding sites whose off-rate constant for Ca 2+ is significantly lower than the Ca 2+ off-rate constant hitherto documented for the divalent ion-binding sites of either cardiac/slow muscle TnC or fast skeletal TnC

The Veracity of Troponin Test Requests for Patients Presenting to the Emergency Department with Chest Pain; A Clinical Audit

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Anita Sabzghabaei

2017-10-01

Full Text Available Introduction: Troponin test is one of the methods for diagnosing acute coronary syndrome, but the overuse and misuse of this test has increased the costs imposed on the health system and the patients. Objective: The present study was conducted to investigate the veracity of troponin test requests for patients presenting to an emergency department with chest pain and examine the effectiveness of training emergency medicine assistants in reducing unnecessary and inappropriate requests in emergency departments. Methods: This clinical audit was conducted in the emergency department of Imam Hossein Hospital, Tehran, Iran, in 2014. Sampling was carried out using the census method and all the cases presenting to the emergency department for whom a troponin test was requested by the emergency medical assistants were included in the research. First, the veracity of the current troponin test requests was assessed; then, training was given to the personnel, and the veracity of the troponin test requests was once again verified after the training was completed. The rate of veracious troponin requests for the patients was measured based on two factors, including the interval between the patients’ admission and the troponin test request, and the interval between the onset of pain and the troponin test request. The veracity of the troponin test request was compared before and after training using the Phi test and Cramer’s V test in IBM SPSS-21. Results: This study examined a total of 500 patients (250 before training and 250 after, who had a mean age of 57.65±18.15 years, including 51.6% men. Significant differences were observed between the mean time of the patients’ admission and the overall and post-training troponin test results (P=0.000, and also between the mean time of the onset of pain and the overall and post-training troponin test results (P=0.000. The number of positive troponin test results did not differ significantly between the patients

Cardiac-specific activation of Cre expression at late fetal development

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Opherk, Jan P.; Yampolsky, Peter; Hardt, Stefan E.; Schoels, Wolfgang; Katus, Hugo A.; Koenen, Michael; Zehelein, Joerg

2007-01-01

In a first step towards dissecting molecular mechanisms that contribute to the development of cardiac diseases, we have generated transgenic mice that express a Cre-GFP fusion protein under the transcriptional control of a 4.3 kb murine cardiac Troponin I gene (cTnI) promoter. Cre-GFP expression, similar in three transgenic lines, is described in one line. In mouse embryos, transgenic for the Cre-GFP and ROSA lacZ reporter allele, first Cre-mediated recombination appeared at 16.5 dpc selectively at the heart. Like the endogenous cTnI gene, transgenic Cre expression showed a slow rise through fetal development that increased neonatally. Bitransgenic hearts, stained at 30 days of age, showed intense signals in ventricular and atrial myocytes while no recombination occurred in other tissues. The delayed onset of Cre activity in cTnI-Cre mice could provide a useful genetic tool to evaluate the function of loxP targeted cardiac genes without interference of recombination during early heart development

Evaluation of Some Inflammatory and Biochemical Markers in Acute Coronary Syndrome

International Nuclear Information System (INIS)

Abdel-Messeih, PH.L.; Nossier, N.M.; Mansour, H.H.

2012-01-01

The term acute coronary syndrome (ACS) encompasses a range of thrombotic coronary artery diseases, including unstable angina (UA) and both ST-segment elevation (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI). Bio markers play an important role in the diagnosis of non-ST-elevation ACS (NSTE-ACS) including unstable angina and non-STEMI. Among these, cardiac troponin and creatine phosphokinase myocardial band appeared to be the most sensitive and specific markers of myocardial injury. The important role of inflammatory processes in the development and progression of atherosclerosis has been clearly established. Different circulating inflammatory bio markers indicating the instability of atherosclerotic plaque have been identified and serve as diagnostic tools for the identification of patients with unstable angina or acute myocardial infarction and to identify risk patients. The present study was carried out on twenty patients with (NSTE-ACS). The level of serum troponin I (cTnI), creatine phosphokinase-total (CPK-T), myocardial band of creatine phosphokinase (CPK-MB), pregnancy associated plasma protein-A (PAPP-A) and highly sensitive C-reactive protein (hsCRP) were determined. The results showed increase in the level of cardiac bio markers (cTnI, CPK-MB, CPK-T) and inflammatory markers (PAPP-A, hsCRP). It could be concluded that the increase in inflammatory markers correlate especially PAPP-A in NSTE-ACS with the increase of cardiac bio markers

Genetic engineering and therapy for inherited and acquired cardiomyopathies.

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Day, Sharlene; Davis, Jennifer; Westfall, Margaret; Metzger, Joseph

2006-10-01

The cardiac myofilaments consist of a highly ordered assembly of proteins that collectively generate force in a calcium-dependent manner. Defects in myofilament function and its regulation have been implicated in various forms of acquired and inherited human heart disease. For example, during cardiac ischemia, cardiac myocyte contractile performance is dramatically downregulated due in part to a reduced sensitivity of the myofilaments to calcium under acidic pH conditions. Over the last several years, the thin filament regulatory protein, troponin I, has been identified as an important mediator of this response. Mutations in troponin I and other sarcomere genes are also linked to several distinct inherited cardiomyopathic phenotypes, including hypertrophic, dilated, and restrictive cardiomyopathies. With the cardiac sarcomere emerging as a central player for such a diverse array of human heart diseases, genetic-based strategies that target the myofilament will likely have broad therapeutic potential. The development of safe vector systems for efficient gene delivery will be a critical hurdle to overcome before these types of therapies can be successfully applied. Nonetheless, studies focusing on the principles of acute genetic engineering of the sarcomere hold value as they lay the essential foundation on which to build potential gene-based therapies for heart disease.

Bayesian Sensitivity Analysis of a Cardiac Cell Model Using a Gaussian Process Emulator

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Chang, Eugene T Y; Strong, Mark; Clayton, Richard H

2015-01-01

Models of electrical activity in cardiac cells have become important research tools as they can provide a quantitative description of detailed and integrative physiology. However, cardiac cell models have many parameters, and how uncertainties in these parameters affect the model output is difficult to assess without undertaking large numbers of model runs. In this study we show that a surrogate statistical model of a cardiac cell model (the Luo-Rudy 1991 model) can be built using Gaussian process (GP) emulators. Using this approach we examined how eight outputs describing the action potential shape and action potential duration restitution depend on six inputs, which we selected to be the maximum conductances in the Luo-Rudy 1991 model. We found that the GP emulators could be fitted to a small number of model runs, and behaved as would be expected based on the underlying physiology that the model represents. We have shown that an emulator approach is a powerful tool for uncertainty and sensitivity analysis in cardiac cell models. PMID:26114610

Quantification of a cardiac biomarker in human serum using extraordinary optical transmission (EOT.

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Tao Ding

Full Text Available Nanoimprinting lithography (NIL is a manufacturing process that can produce macroscale surface areas with nanoscale features. In this paper, this technique is used to solve three fundamental issues for the application of localized surface plasmonic resonance (LSPR in practical clinical measurements: assay sensitivity, chip-to-chip variance, and the ability to perform assays in human serum. Using NIL, arrays of 140 nm square features were fabricated on a sensing area of 1.5 mm x 1.5 mm with low cost. The high reproducibility of NIL allowed for the use of a one-chip, one-measurement approach with 12 individually manufactured surfaces with minimal chip-to-chip variations. To better approximate a real world setting, all chips were modified with a biocompatible, multi-component monolayer and inter-chip variability was assessed by measuring a bioanalyte standard (2.5-75 ng/ml in the presence of a complex biofluid, human serum. In this setting, nanoimprinted LSPR chips were able to provide sufficient characteristics for a 'low-tech' approach to laboratory-based bioanalyte measurement, including: 1 sufficient size to interface with a common laboratory light source and detector without the need for a microscope, 2 high sensitivity in serum with a cardiac troponin limit of detection of 0.55 ng/ml, and 3 very low variability in chip manufacturing to produce a figure of merit (FOM of 10.5. These findings drive LSPR closer to technical comparability with ELISA-based assays while preserving the unique particularities of a LSPR based sensor, suitability for multiplexing and miniaturization, and point-of-care detections.

44. Copeptin as early marker of acute non-ST elevation myocardial infarction in patients suspected with acute coronary syndrome

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S. Rafla

2016-07-01

Full Text Available Rapid diagnosis and management of AMI have great impact on morbidity and mortality. Diagnosis which is based on elevation of cardiac biomarkers has its limitations. Copeptin is the C-terminal part of the vasopressin prohormone. The pathophysiology mode of release should theoretically add diagnostic information of cardiac cell necrosis. One of the major limitations of cardiac biomarkers is the delayed release in circulation. So looking for a new marker with a short diagnostic time window is needed. Aim is to determine the role of copeptin as an early marker for acute non-ST elevation MI (NSTEMI. This study included 88 patients with chest pain. They were divided into 2 groups. Group (1; included 30 patients with diagnosis of NSTEMI. Diagnosis of AMI was established according to the universal definition of MI. Group (2; included 58 patients with diagnosis of unstable angina (UA. Full medical history, physical examination, 12 lead ECG, random blood glucose level, renal function, total cholesterol, triglyceride, cardiac troponin I and Copeptin were obtained on admission. Follow up cardiac troponin I was done. Inclusion criteria: Defined as chest pain of ⩽6 h duration since onset, suggestive of myocardial ischemia, and lasting >20 min. at rest. Exclusion criteria: Patients with positive First cardiac troponin were rolled out, patients with ST segment elevation were rolled out. Other exclusion criteria: Patients presenting after a cardiac arrest, Trauma or major surgery within the last 4 week; pregnancy; IV drug abuse; age less than 18 years; shock and sepsis. Patients who were included had second troponin I re- done and copeptin analysis done. In group 1 (NSTEMI 28 patients had ECG changes and only 2 had NSTEMI without ECG changes. In group 2 (UA 23 patients had ECG changes and 35 patients had normal ECG. Males and females were 49 and 39. Age in G1 and G2 was 60 ± 4 and 53 ± 5. Copeptin analysis was done 6 h after Infarction or chest pain

Frequency and significance of troponin T elevation in acute ischemic stroke

DEFF Research Database (Denmark)

Jensen, Jesper K.; Kristensen, Søren R.; Bak, Søren

2007-01-01

Elevated levels of troponin have been reported in patients with acute ischemic stroke. In this prospective study, the prevalence and characteristics of troponin elevation were examined in 244 patients with acute ischemic stroke but without overt ischemic heart disease. Troponin T (TnT) and creatine...... for a mean of 19 +/- 7 months, with all-cause mortality as the clinical end point. Elevated levels of TnT (>0.03 micro g/L) and creatine kinase-MB (> or =10 micro g/L) were observed in 10% and 9% of patients, respectively. Patients with elevated TnT had higher frequencies of heart and/or renal failure....... Perfusion abnormalities on myocardial perfusion scintigraphy at rest were not more frequent or pronounced in patients with TnT levels of > or =0.10 micro g/L than in the control group. Only 7 patients (3%) had elevations of TnT or creatine kinase-MB and electrocardiographic changes suggesting acute...

Sensitivity Analysis of Vagus Nerve Stimulation Parameters on Acute Cardiac Autonomic Responses: Chronotropic, Inotropic and Dromotropic Effects.

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David Ojeda

Full Text Available Although the therapeutic effects of Vagus Nerve Stimulation (VNS have been recognized in pre-clinical and pilot clinical studies, the effect of different stimulation configurations on the cardiovascular response is still an open question, especially in the case of VNS delivered synchronously with cardiac activity. In this paper, we propose a formal mathematical methodology to analyze the acute cardiac response to different VNS configurations, jointly considering the chronotropic, dromotropic and inotropic cardiac effects. A latin hypercube sampling method was chosen to design a uniform experimental plan, composed of 75 different VNS configurations, with different values for the main parameters (current amplitude, number of delivered pulses, pulse width, interpulse period and the delay between the detected cardiac event and VNS onset. These VNS configurations were applied to 6 healthy, anesthetized sheep, while acquiring the associated cardiovascular response. Unobserved VNS configurations were estimated using a Gaussian process regression (GPR model. In order to quantitatively analyze the effect of each parameter and their combinations on the cardiac response, the Sobol sensitivity method was applied to the obtained GPR model and inter-individual sensitivity markers were estimated using a bootstrap approach. Results highlight the dominant effect of pulse current, pulse width and number of pulses, which explain respectively 49.4%, 19.7% and 6.0% of the mean global cardiovascular variability provoked by VNS. More interestingly, results also quantify the effect of the interactions between VNS parameters. In particular, the interactions between current and pulse width provoke higher cardiac effects than the changes on the number of pulses alone (between 6 and 25% of the variability. Although the sensitivity of individual VNS parameters seems similar for chronotropic, dromotropic and inotropic responses, the interacting effects of VNS parameters

Comparison of usefulness of N-terminal pro-brain natriuretic peptide as an independent predictor of cardiac function among admission cardiac serum biomarkers in patients with anterior wall versus nonanterior wall ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

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Haeck, Joost D E; Verouden, Niels J W; Kuijt, Wichert J; Koch, Karel T; Van Straalen, Jan P; Fischer, Johan; Groenink, Maarten; Bilodeau, Luc; Tijssen, Jan G P; Krucoff, Mitchell W; De Winter, Robbert J

2010-04-15

The purpose of the present study was to determine the prognostic value of N-terminal pro-brain natriuretic peptide (NT-pro-BNP), among other serum biomarkers, on cardiac magnetic resonance (CMR) imaging parameters of cardiac function and infarct size in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. We measured NT-pro-BNP, cardiac troponin T, creatinine kinase-MB fraction, high-sensitivity C-reactive protein, and creatinine on the patients' arrival at the catheterization laboratory in 206 patients with ST-segment elevation myocardial infarction. The NT-pro-BNP levels were divided into quartiles and correlated with left ventricular function and infarct size measured by CMR imaging at 4 to 6 months. Compared to the lower quartiles, patients with nonanterior wall myocardial infarction in the highest quartile of NT-pro-BNP (> or = 260 pg/ml) more often had a greater left ventricular end-systolic volume (68 vs 39 ml/m(2), p pro-BNP level of > or = 260 pg/ml was the strongest independent predictor of left ventricular ejection fraction in patients with nonanterior wall myocardial infarction compared to the other serum biomarkers (beta = -5.8; p = 0.019). In conclusion, in patients with nonanterior wall myocardial infarction undergoing primary percutaneous coronary intervention, an admission NT-pro-BNP level of > or = 260 pg/ml was a strong, independent predictor of left ventricular function assessed by CMR imaging at follow-up. Our findings suggest that NT-pro-BNP, a widely available biomarker, might be helpful in the early risk stratification of patients with nonanterior wall myocardial infarction. Copyright 2010 Elsevier Inc. All rights reserved.

N-terminal pro-brain natriuretic peptide and cardiac troponin I for the prognostic utility in elderly patients with severe sepsis or septic shock in intensive care unit: A retrospective study.

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Cheng, Hui; Fan, Wei-Ze; Wang, Sheng-Chi; Liu, Zhao-Hui; Zang, Hui-Ling; Wang, Li-Zhong; Liu, Hong-Juan; Shen, Xiao-Hui; Liang, Shao-Qing

2015-06-01

Using biomarkers to predict mortality in patient with severe sepsis or septic shock is of importance, as these patients frequently have high mortality and unsatisfied outcome. N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) play extremely important roles in prognostic value in the mortality of severe sepsis and septic shock. The present study was retrospectively designed to evaluate the predicting mortality of NT-proBNP and cTnI in elderly patients with severe sepsis or septic shock administered in the intensive care unit (ICU) and also to evaluate whether the predicting ability of Acute Physiology and Chronic Health Evaluation II (APACHE-II) score or C-reactive protein (CRP) was increased in combination with the biomarkers. A cohort of 430 patients (aged ≥65 years) with severe sepsis or septic shock admitted to our ICU between October 2011 and December 2013 was included in the study. Patient data including clinical, laboratory, and survival and mortality were collected. All patients were examined with NT-proBNP, cTnI, CRP, and APACHE-II score and were categorized as the survived and deceased groups according to the outcome 30 days after ICU treatment. The levels of NT-proBNP and cTnI (P pro-brain natriuretic peptide and cTnI were superior to CRP in predicting mortality. The predicting ability of APACHE-II score was improved only when combined with NT-proBNP and cTnI. Copyright © 2014 Elsevier Inc. All rights reserved.

The Role of Levosimendan in Patients with Decreased Left Ventricular Function Undergoing Cardiac Surgery

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Marija Bozhinovska

2016-06-01

Full Text Available The postoperative low cardiac output is one of the most important complications following cardiac surgery and is associated with increased morbidity and mortality. The condition requires inotropic support to achieve adequate hemodynamic status and tissue perfusion. While catecholamines are utilised as a standard therapy in cardiac surgery, their use is limited due to increased oxygen consumption. Levosimendan is calcium sensitising inodilatator expressing positive inotropic effect by binding with cardiac troponin C without increasing oxygen demand. Furthermore, the drug opens potassium ATP (KATP channels in cardiac mitochondria and in the vascular muscle cells, showing cardioprotective and vasodilator properties, respectively. In the past decade, levosimendan demonstrated promising results in treating patients with reduced left ventricular function when administered in peri- or post- operative settings. In addition, pre-operative use of levosimendan in patients with severely reduced left ventricular ejection fraction may reduce the requirements for postoperative inotropic support, mechanical support, duration of intensive care unit stay as well as hospital stay and a decrease in post-operative mortality. However, larger studies are needed to clarify clinical advantages of levosimendan versus conventional inotropes.

A randomized cross-over study of the acute effects of running 5 km on glucose, insulin, metabolic rate, cortisol and Troponin T.

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Keselman, Boris; Vergara, Marta; Nyberg, Sofia; Nystrom, Fredrik H

2017-01-01

We aimed to study the impact by running 5 km, at maximal speed, on the normal variations of metabolic variables related to glucose, insulin, insulin sensitivity, cortisol, glucagon, Troponin T and metabolic rate. Five women and 12 men 25.7±5.2 years of age with a body-mass-index of 22.5±2.3 kg/m2 where recruited to run 5 km at individual maximal speed in the morning, and to a corresponding day of rest, followed by standardized breakfast and lunch meals. Blood sampling and measurement of indirect calorimetry were done before and after meals. The participants were randomized regarding the order of the two trial-days in this cross-over study. Insulin and cortisol levels were higher, and insulin sensitivity was lower, on the race-day compared with the day of rest (linear mixed model: pdays (p = 0.29 and p = 0.53, respectively). When analyzing specific time-points we found that glucose increased from 5.01±0.37 mmol/l to 6.36 ± 1.3 mmol/l, pindex of serum sensitivity, 1/(log10insulin+log10glucose), was lowered post-race, p<0.0001. Serum cortisol levels increased from 408±137 nmol/l to 644±171 nmol/l, p<0.0001, post-race while serum glucagon levels were unaffected. Troponin T was detectable in serum post-race in 12 out of the 17 participants and reached or surpassed the clinical reference level of 15 ng/l in three subjects. Post-race electrocardiograms displayed no pathologies. Relatively short running-races can apparently induce a reduction in insulin sensitivity that is not fully compensated by concomitantly increased insulin secretion intended to ensure euglycemia. Since also Troponin T was detected in plasma in a majority of the participants, our data suggest that it is possible to induce considerable metabolic stress by running merely 5 km, when striving for maximal speed.

Trauma-induced secondary cardiac injury is associated with hyperacute elevations in inflammatory cytokines.

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De'Ath, Henry D; Manson, Joanna; Davenport, Ross; Glasgow, Simon; Renfrew, Ian; Davies, L Ceri; Uppal, Rakesh; Brohi, Karim

2013-05-01

Clinical evidence supports the existence of a trauma-induced secondary cardiac injury. Experimental research suggests inflammation as a possible mechanism. The study aimed to determine if there was an early association between inflammation and secondary cardiac injury in trauma patients. A cohort study of critically injured patients between January 2008 and January 2010 was undertaken. Levels of the cardiac biomarkers troponin I and heart-specific fatty acid-binding protein and the cytokines tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-1β, and IL-8 were measured on admission to hospital, and again at 24 and 72 h. Participants were reviewed for adverse cardiac events (ACEs) and in-hospital mortality. Of 135 patients recruited, 18 (13%) had an ACE. Patients with ACEs had higher admission plasma levels of TNF-α (5.4 vs. 3.8 pg/mL; P = 0.03), IL-6 (140 vs. 58.9 pg/mL, P = 0.009), and IL-8 (19.3 vs. 9.1 pg/mL, P = 0.03) compared with those without events. Hour 24 cytokines were not associated with events, but IL-8 (14.5 vs. 5.8 pg/mL; P = 0.01) and IL-1β (0.55 vs. 0.19 pg/mL; P = 0.04) were higher in patients with ACEs at 72 hours. Admission IL-6 was independently associated with heart-specific fatty acid-binding protein increase (P < 0.05). Patients who presented with an elevated troponin I combined with either an elevated TNF-α (relative risk [RR], 11.0; 95% confidence interval [CI], 1.8-66.9; P = 0.015), elevated IL-6 (RR, 17.3; 95% CI, 2.9-101.4; P = 0.001), or elevated IL-8 (RR, 15.0; 95% CI, 3.1-72.9; P = 0.008) were at the highest risk of in-hospital death when compared with individuals with normal biomarker and cytokine values. There is an association between hyperacute elevations in inflammatory cytokines with cardiac injury and ACEs in critically injured patients. Biomarker evidence of cardiac injury and inflammation on admission is associated with a higher risk of in-hospital death.

OptoDyCE: Automated system for high-throughput all-optical dynamic cardiac electrophysiology

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Klimas, Aleksandra; Yu, Jinzhu; Ambrosi, Christina M.; Williams, John C.; Bien, Harold; Entcheva, Emilia

2016-02-01

In the last two decades, market were due to cardiac toxicity, where unintended interactions with ion channels disrupt the heart's normal electrical function. Consequently, all new drugs must undergo preclinical testing for cardiac liability, adding to an already expensive and lengthy process. Recognition that proarrhythmic effects often result from drug action on multiple ion channels demonstrates a need for integrative and comprehensive measurements. Additionally, patient-specific therapies relying on emerging technologies employing stem-cell derived cardiomyocytes (e.g. induced pluripotent stem-cell-derived cardiomyocytes, iPSC-CMs) require better screening methods to become practical. However, a high-throughput, cost-effective approach for cellular cardiac electrophysiology has not been feasible. Optical techniques for manipulation and recording provide a contactless means of dynamic, high-throughput testing of cells and tissues. Here, we consider the requirements for all-optical electrophysiology for drug testing, and we implement and validate OptoDyCE, a fully automated system for all-optical cardiac electrophysiology. We demonstrate the high-throughput capabilities using multicellular samples in 96-well format by combining optogenetic actuation with simultaneous fast high-resolution optical sensing of voltage or intracellular calcium. The system can also be implemented using iPSC-CMs and other cell-types by delivery of optogenetic drivers, or through the modular use of dedicated light-sensitive somatic cells in conjunction with non-modified cells. OptoDyCE provides a truly modular and dynamic screening system, capable of fully-automated acquisition of high-content information integral for improved discovery and development of new drugs and biologics, as well as providing a means of better understanding of electrical disturbances in the heart.

Dioxin-induced acute cardiac mitochondrial oxidative damage and increased activity of ATP-sensitive potassium channels in Wistar rats

International Nuclear Information System (INIS)

Pereira, Susana P.; Pereira, Gonçalo C.; Pereira, Cláudia V.; Carvalho, Filipa S.; Cordeiro, Marília H.; Mota, Paula C.; Ramalho-Santos, João; Moreno, António J.; Oliveira, Paulo J.

2013-01-01

The environmental dioxin 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is classified as a Group 1 human carcinogen and teratogenic agent. We hypothesize that TCDD-induced oxidative stress may also interfere with mitochondrial ATP-sensitive potassium channels (mitoKATP), which are known to regulate and to be regulated by mitochondrial redox state. We investigated the effects of an acute treatment of male Wistar rats with TCDD (50 μg/kg i.p.) and measured the regulation of cardiac mitoKATP. While the function of cardiac mitochondria was slightly depressed, mitoKATP activity was 52% higher in animals treated with TCDD. The same effects were not observed in liver mitochondria isolated from the same animals. Our data also shows that regulation of mitochondrial ROS production by mitoKATP activity is different in both groups. To our knowledge, this is the first report to show that TCDD increases mitoKATP activity in the heart, which may counteract the increased oxidative stress caused by the dioxin during acute exposure. -- Highlights: •Acute TCDD treatment of Wistar rats causes cardiac oxidative stress. •Acute TCDD treatment causes cardiac mitochondrial alterations. •Mitochondrial liver vs. heart alterations are distinct. •TCDD treatment resulted in altered activity of cardiac mitochondrial K-ATP channels. -- Dioxin alters the regulation of cardiac mitochondrial ATP-sensitive potassium channels and disturbs mitochondrial physiology

Comparison of low-energy versus high-energy biphasic defibrillation shocks following prolonged ventricular fibrillation.

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Walcott, Gregory P; Melnick, Sharon B; Killingsworth, Cheryl R; Ideker, Raymond E

2010-01-01

Since the initial development of the defibrillator, there has been concern that, while delivery of a large electric shock would stop fibrillation, it would also cause damage to the heart. This concern has been raised again with the development of the biphasic defibrillator. To compare defibrillation efficacy, postshock cardiac function, and troponin I levels following 150-J and 360-J shocks. Nineteen swine were anesthetized with isoflurane and instrumented with pressure catheters in the left ventricle, aorta, and right atrium. The animals were fibrillated for 6 minutes, followed by defibrillation with either low-energy (n = 8) or high-energy (n = 11) shocks. After defibrillation, chest compressions were initiated and continued until return of spontaneous circulation (ROSC). Epinephrine, 0.01 mg/kg every 3 minutes, was given for arterial blood pressure < 50 mmHg. Hemodynamic parameters were recorded for four hours. Transthoracic echocardiography was performed and troponin I levels were measured at baseline and four hours following ventricular fibrillation (VF). Survival rates at four hours were not different between the two groups (low-energy, 5 of 8; high-energy, 7 of 11). Results for arterial blood pressure, positive dP/dt (first derivative of pressure measured over time, a measure of left ventricular contractility), and negative dP/dt at the time of lowest arterial blood pressure (ABP) following ROSC were not different between the two groups (p = not significant [NS]), but were lower than at baseline. All hemodynamic measures returned to baseline by four hours. Ejection fractions, stroke volumes, and cardiac outputs were not different between the two groups at four hours. Troponin I levels at four hours were not different between the two groups (12 +/- 11 ng/mL versus 21 +/- 26 ng/mL, p = NS) but were higher at four hours than at baseline (19 +/- 19 ng/mL versus 0.8 +/- 0.5 ng/mL, p < 0.05, groups combined). Biphasic 360-J shocks do not cause more cardiac damage

Prospective surveillance for cardiac adverse events in healthy adults receiving modified vaccinia Ankara vaccines: a systematic review.

Science.gov (United States)

Elizaga, Marnie L; Vasan, Sandhya; Marovich, Mary A; Sato, Alicia H; Lawrence, Dale N; Chaitman, Bernard R; Frey, Sharon E; Keefer, Michael C

2013-01-01

Vaccinia-associated myo/pericarditis was observed during the US smallpox vaccination (DryVax) campaign initiated in 2002. A highly-attenuated vaccinia strain, modified vaccinia Ankara (MVA) has been evaluated in clinical trials as a safer alternative to DryVax and as a vector for recombinant vaccines. Due to the lack of prospectively collected cardiac safety data, the US Food and Drug Administration required cardiac screening and surveillance in all clinical trials of MVA since 2004. Here, we report cardiac safety surveillance from 6 phase I trials of MVA vaccines. Four clinical research organizations contributed cardiac safety data using common surveillance methods in trials administering MVA or recombinant MVA vaccines to healthy participants. 'Routine cardiac investigations' (ECGs and cardiac enzymes obtained 2 weeks after injections of MVA or MVA-HIV recombinants, or placebo-controls), and 'Symptom-driven cardiac investigations' are reported. The outcome measure is the number of participants who met the CDC-case definition for vaccinia-related myo/pericarditis or who experienced cardiac adverse events from an MVA vaccine. Four hundred twenty-five study participants had post-vaccination safety data analyzed, 382 received at least one MVA-containing vaccine and 43 received placebo; 717 routine ECGs and 930 cardiac troponin assays were performed. Forty-five MVA recipients (12%) had additional cardiac testing performed; 22 for cardiac symptoms, 19 for ECG/laboratory changes, and 4 for cardiac symptoms with an ECG/laboratory change. No participant had evidence of symptomatic or asymptomatic myo/pericarditis meeting the CDC-case definition and judged to be related to an MVA vaccine. Prospective surveillance of MVA recipients for myo/pericarditis did not detect cardiac adverse reactions in 382 study participants. ClinicalTrials.gov NCT00082446 NCT003766090 NCT00252148 NCT00083603 NCT00301184 NCT00428337.

Prospective surveillance for cardiac adverse events in healthy adults receiving modified vaccinia Ankara vaccines: a systematic review.

Directory of Open Access Journals (Sweden)

Marnie L Elizaga

Full Text Available Vaccinia-associated myo/pericarditis was observed during the US smallpox vaccination (DryVax campaign initiated in 2002. A highly-attenuated vaccinia strain, modified vaccinia Ankara (MVA has been evaluated in clinical trials as a safer alternative to DryVax and as a vector for recombinant vaccines. Due to the lack of prospectively collected cardiac safety data, the US Food and Drug Administration required cardiac screening and surveillance in all clinical trials of MVA since 2004. Here, we report cardiac safety surveillance from 6 phase I trials of MVA vaccines.Four clinical research organizations contributed cardiac safety data using common surveillance methods in trials administering MVA or recombinant MVA vaccines to healthy participants. 'Routine cardiac investigations' (ECGs and cardiac enzymes obtained 2 weeks after injections of MVA or MVA-HIV recombinants, or placebo-controls, and 'Symptom-driven cardiac investigations' are reported. The outcome measure is the number of participants who met the CDC-case definition for vaccinia-related myo/pericarditis or who experienced cardiac adverse events from an MVA vaccine.Four hundred twenty-five study participants had post-vaccination safety data analyzed, 382 received at least one MVA-containing vaccine and 43 received placebo; 717 routine ECGs and 930 cardiac troponin assays were performed. Forty-five MVA recipients (12% had additional cardiac testing performed; 22 for cardiac symptoms, 19 for ECG/laboratory changes, and 4 for cardiac symptoms with an ECG/laboratory change. No participant had evidence of symptomatic or asymptomatic myo/pericarditis meeting the CDC-case definition and judged to be related to an MVA vaccine.Prospective surveillance of MVA recipients for myo/pericarditis did not detect cardiac adverse reactions in 382 study participants.ClinicalTrials.gov NCT00082446 NCT003766090 NCT00252148 NCT00083603 NCT00301184 NCT00428337.

Raised cardiac enzymes in sepsis with renal failure: An encompassing umbrella or a masquerader?

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Dilip Gude

2014-01-01

Full Text Available Elevation of cardiac enzymes and troponins particularly in settings of sepsis and renal failure may cloud the diagnostic picture of acute coronary syndrome in many cases. Interpretation of such elevated enzymes thus warrants caution. It necessitates adequate awareness amongst clinicians, of conditions with such elevation in the absence of myocardial ischemia/infarction as well as those that harbinger false positives. We discuss one such case that posed a diagnostic dilemma and review the pertinent literature.

Evaluation of acute cardiac and chest wall damage after shocks with a subcutaneous implantable cardioverter defibrillator in Swine.

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Killingsworth, Cheryl R; Melnick, Sharon B; Litovsky, Silvio H; Ideker, Raymond E; Walcott, Gregory P

2013-10-01

A subcutaneous implantable cardioverter defibrillator (S-ICD) could ease placement and reduce complications of transvenous ICDs, but requires more energy than transvenous ICDs. Therefore we assessed cardiac and chest wall damage caused by the maximum energy shocks delivered by both types of clinical devices. During sinus rhythm, anesthetized pigs (38 ± 6 kg) received an S-ICD (n = 4) and five 80-Joule (J) shocks, or a transvenous ICD (control, n = 4) and five 35-J shocks. An inactive S-ICD electrode was implanted into the same control pigs to study implant trauma. All animals survived 24 hours. Troponin I and creatine kinase muscle isoenzyme (CK-MM) were measured as indicators of myocardial and skeletal muscle injury. Histopathological injury of heart, lungs, and chest wall was assessed using semiquantitative scoring. Troponin I was significantly elevated at 4 hours and 24 hours (22.6 ± 16.3 ng/mL and 3.1 ± 1.3 ng/mL; baseline 0.07 ± 0.09 ng/mL) in control pigs but not in S-ICD pigs (0.12 ± 0.11 ng/mL and 0.13 ± 0.13 ng/mL; baseline 0.06 ± 0.03 ng/mL). CK-MM was significantly elevated in S-ICD pigs after shocks (6,544 ± 1,496 U/L and 9,705 ± 6,240 U/L; baseline 704 ± 398 U/L) but not in controls. Electrocardiogram changes occurred postshock in controls but not in S-ICD pigs. The myocardium and lungs were histologically normal in both groups. Subcutaneous injury was greater in S-ICD compared to controls. Although CK-MM suggested more skeletal muscle injury in S-ICD pigs, significant cardiac, lung, and chest wall histopathological changes were not detected in either group. Troponin I data indicate significantly less cardiac injury from 80-J S-ICD shocks than 35-J transvenous shocks. ©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.

Up-regulation of alpha-smooth muscle actin in cardiomyocytes from non-hypertrophic and non-failing transgenic mouse hearts expressing N-terminal truncated cardiac troponin I

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Stephanie Kern

2014-01-01

Full Text Available We previously reported that a restrictive N-terminal truncation of cardiac troponin I (cTnI-ND is up-regulated in the heart in adaptation to hemodynamic stresses. Over-expression of cTnI-ND in the hearts of transgenic mice revealed functional benefits such as increased relaxation and myocardial compliance. In the present study, we investigated the subsequent effect on myocardial remodeling. The alpha-smooth muscle actin (α-SMA isoform is normally expressed in differentiating cardiomyocytes and is a marker for myocardial hypertrophy in adult hearts. Our results show that in cTnI-ND transgenic mice of between 2 and 3 months of age (young adults, a significant level of α-SMA is expressed in the heart as compared with wild-type animals. Although blood vessel density was increased in the cTnI-ND heart, the mass of smooth muscle tissue did not correlate with the increased level of α-SMA. Instead, immunocytochemical staining and Western blotting of protein extracts from isolated cardiomyocytes identified cardiomyocytes as the source of increased α-SMA in cTnI-ND hearts. We further found that while a portion of the up-regulated α-SMA protein was incorporated into the sarcomeric thin filaments, the majority of SMA protein was found outside of myofibrils. This distribution pattern suggests dual functions for the up-regulated α-SMA as both a contractile component to affect contractility and as possible effector of early remodeling in non-hypertrophic, non-failing cTnI-ND hearts.

Non-invasive quick diagnosis of cardiovascular problems from visible and invisible abnormal changes with increased cardiac troponin I appearing on cardiovascular representation areas of the eyebrows, left upper lip, etc. of the face & hands: beneficial manual stimulation of hands for acute anginal chest pain, and important factors in safe, effective treatment.

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Omura, Yoshiaki; Jones, Marilyn K; Duvvi, Harsha; Shimotsuura, Yasuhiro; Ohki, Motomu; Rodriques, Aaron

2014-01-01

Our previous study indicated that there are at least 7 cardiovascular representation areas on the face, including the "Eyebrows", both sides of the "Nose", "Lelt Upper Lip" and the "Outside of the corner of both sides of the mouth," in addition to 2 areas in each hand. When there are cardiovascular problems, some of the heart representation areas of these areas often show the following changes: 1) Most distinctive visible changes such as the initial whitening with or without long white hair, then hair loss and complete disappearance of the hairs of the heart representation area of "Eyebrows" 2) Invisible biochemical changes that happen in heart representation areas at the "Left Upper Lips", 3) "Nose" below eye level as well as 4) "3rd segment of Middle Finger of Hands." Most distinctive visible & invisible changes are found in heart representation areas on the "Eyebrow", located nearest to the midline of face, where the color of the hairs becomes white compared with the rest of the Eyebrow. Then the cardiovascular problem advances, and hair starts disappearing. When there are no hairs at the heart representation areas of the Eyebrow, usually Cardiac Troponin I is increased to a very serious, abnormal high value. Most of the cardiovascular representation areas of the face show, regardless of presence or absence of visible change. When there is a cardiovascular problem, not only simple Bi-Digital O-Ring Test can detect without using any instrument in several minutes but also, corresponding biochemical changes of abnormally increased Cardiac Troponin I level can often be detected non-invasively from these Organ Representation Areas of Face & Hands, although changes in Eyebrows, L-Upper Lip & 3rd segment of middle fingers are clinically the most reliable changes & easy to identify the locations. Manual Stimulation of Hand's heart representation areas often eliminated acute anginal chest pain before medical help became available. Important factors for safe, effective

Metabolic and cardiac changes in high cholesterol-fructose-fed rats

DEFF Research Database (Denmark)

Axelsen, Lene N; Pedersen, Henrik D; Petersen, Jørgen S

2010-01-01

Introduction: High cholesterol-fructose (HCF) fed rats have previously been described as an animal model of impaired cardiac insulin signaling and decreased contractile performance. In this study, we evaluated the metabolic and cardiac effects of a HCF diet in rats. Methods: Male Sprague-Dawley r......Introduction: High cholesterol-fructose (HCF) fed rats have previously been described as an animal model of impaired cardiac insulin signaling and decreased contractile performance. In this study, we evaluated the metabolic and cardiac effects of a HCF diet in rats. Methods: Male Sprague...

Solid-Phase Immunoassay of Polystyrene-Encapsulated Semiconductor Coreshells for Cardiac Marker Detection

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Sanghee Kim

2012-01-01

Full Text Available A solid-phase immunoassay of polystyrene-encapsulated semiconductor nanoparticles was demonstrated for cardiac troponin I (cTnI detection. CdSe/ZnS coreshells were encapsulated with a carboxyl-functionalized polystyrene nanoparticle to capture the target antibody through a covalent bonding and to eliminate the photoblinking and toxicity of semiconductor luminescent immunosensor. The polystyrene-encapsulated CdSe/ZnS fluorophores on surface-modified glass chip identified cTnI antigens at the level of ~ng/mL. It was an initial demonstration of diagnostic chip for monitoring a cardiovascular disease.

Predictors of major postoperative cardiac complications in a surgical ICU.

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Maia, Paula C; Abelha, Fernando J

2008-03-01

Cardiovascular complications are associated with increased mortality and morbidity during the postoperative period, resulting in longer hospital stay and higher treatment costs. The aim of this study was to identify predictors of major postoperative cardiac complications. 187 patients undergoing noncardiac surgery, admitted to a surgical intensive care unit (ICU) between November 2004 and April 2005. Variables recorded were age, gender, American Society of Anesthesiologists (ASA) physical status, type and magnitude of surgery, mortality, ICU and hospital length of stay (LOS), Simplified Acute Physiology Score II (SAPS II), cardiac troponin I (cTnI) at postoperative day 0, 1, 2 and 3, history of hypertension, hyperlipidemia, Revised Cardiac Risk Index (RCRI) score, major cardiac events (MCE): acute myocardial infarction (AMI), pulmonary edema (PE), ventricular fibrillation (VF) or primary cardiac arrest (PCA). Correlations between variables and MCE were made by univariate analysis by simple logistic regression with odds ratio (OR) and 95% confidence interval (95% CI). Total of 14 MCE: 9 AMI, 1 VF, 4 PE. Significant risk factors for MCE were high-risk surgery (OR 8.26, 95% CI 1.76-38.85, p = 0.008), RCRI > or = 2 (OR 4.0, 95% CI 1.22-13.16, p = 0.022), admission cTnI (OR 1.46, 95% CI 1.07-1.99, p = 0.018); day 1 cTnI (OR 1.75, 95% CI 1.27-2.41, p = 0.001); day 2 cTnI (OR 2.23, 95% CI 1.24-3.98, p = 0.007), SAPS II (OR 1.08, 95% CI 1.04-1.12, p or = 2, cTnI levels and SAPS II were predictors of postoperative MCE. Patients with MCE had longer ICU stay and higher mortality rate.

Usefulness of the troponin-ejection fraction product to differentiate stress cardiomyopathy from ST-segment elevation myocardial infarction.

Science.gov (United States)

Nascimento, Francisco O; Yang, Solomon; Larrauri-Reyes, Maiteder; Pineda, Andres M; Cornielle, Vertilio; Santana, Orlando; Heimowitz, Todd B; Stone, Gregg W; Beohar, Nirat

2014-02-01

The presentation of stress cardiomyopathy (SC) with nonobstructive coronary artery disease mimics that of ST-segment elevation myocardial infarction (STEMI) due to coronary occlusion. No single parameter has been successful in differentiating the 2 entities. We thus sought to develop a noninvasive clinical tool to discriminate between these 2 conditions. We retrospectively reviewed 59 consecutive cases of SC at our institution from July 2005 through June 2011 and compared those with 60 consecutives cases of angiographically confirmed STEMI treated with primary percutaneous coronary intervention in the same period. All patients underwent acute echocardiography, and the peak troponin I level was determined. The troponin-ejection fraction product (TEFP) was derived by multiplying the peak troponin I level and the echocardiographically derived left ventricular ejection fraction. Comparing the SC and STEMI groups, the mean left ventricular ejection fraction at the time of presentation was 30 ± 9% versus 44 ± 11%, respectively (p statistic 0.91 ± 0.02, p <0.001). In conclusion, for patients not undergoing emergent angiography, the TEFP may be used with high accuracy to differentiate SC with nonobstructive coronary artery disease from true STEMI due to coronary occlusion. Copyright © 2014 Elsevier Inc. All rights reserved.

Predictors of Sudden Cardiac Death in Doberman Pinschers with Dilated Cardiomyopathy.

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Klüser, L; Holler, P J; Simak, J; Tater, G; Smets, P; Rügamer, D; Küchenhoff, H; Wess, G

2016-05-01

Doberman Pinschers with dilated cardiomyopathy (DCM) are at high risk of sudden cardiac death (SCD). Risk factors for SCD are poorly defined. To assess cardiac biomarkers, Holter-ECG, echocardiographic variables and canine characteristics in a group of Doberman Pinschers with DCM dying of SCD and in a DCM control group to identify factors predicting SCD. A longitudinal prospective study was performed in 95 Doberman Pinschers with DCM. Forty-one dogs died within 3 months after the last cardiac examination (SCD-group) and were compared to 54 Doberman Pinschers with DCM surviving 1 year after inclusion. Holter-ECG, echocardiography, measurement of N-terminal prohormone of brain-natriuretic peptide (NT-proBNP), and cardiac Troponin I (cTnI) concentrations were recorded for all dogs. Volume overload of the left ventricle (left ventricular end-diastolic volume (LVEDV/BSA) > 91.3 mL/m²) was the single best variable to predict SCD. The probability of SCD increases 8.5-fold (CI0.95  = 0.8-35.3) for every 50 mL/m²-unit increment in LVEDV/BSA. Ejection fraction (EF), left ventricular end-systolic volume (LVESV/BSA) and NT-proBNP were highly correlated with LVEDV/BSA (r = -0.63, 0.96, 0.86, respectively). Generated conditional inference trees (CTREEs) revealed that the presence of ventricular tachycardia (VT), increased concentration of cTnI, and the fastest rate (FR) of ventricular premature complexes (VPC) ≥260 beats per minute (bpm) are additional important variables to predict SCD. Conditional inference trees provided in this study might be useful for risk assessment of SCD in Doberman Pinschers with DCM. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Quality specification and status of internal quality control of cardiac biomarkers in China from 2011 to 2016.

Science.gov (United States)

Li, Tingting; Wang, Wei; Zhao, Haijian; He, Falin; Zhong, Kun; Yuan, Shuai; Wang, Zhiguo

2017-09-07

This study aimed to investigate the status of internal quality control (IQC) for cardiac biomarkers from 2011 to 2016 so that we can have overall knowledge of the precision level of measurements in China and set appropriate precision specifications. Internal quality control data of cardiac biomarkers, including creatinine kinase MB (CK-MB) (μg/L), CK-MB(U/L), myoglobin (Mb), cardiac troponin I (cTnI), cardiac troponin T (cTnT), and homocysteines (HCY), were collected by a web-based external quality assessment (EQA) system. Percentages of laboratories meeting five precision quality specifications for current coefficient of variations (CVs) were calculated. Then, appropriate precision specifications were chosen for these six analytes. Finally, the CVs and IQC practice were further analyzed with different grouping methods. The current CVs remained nearly constant for 6 years. cTnT had the highest pass rates every year against five specifications, whereas HCY had the lowest pass rates. Overall, most analytes had a satisfactory performance (pass rates >80%), except for HCY, if one-third TEa or the minimum specification were employed. When the optimal specification was applied, the performance of most analytes was frustrating (pass rates < 60%) except for cTnT. The appropriate precision specifications of Mb, cTnI, cTnT and HCY were set as current CVs less than 9.20%, 9.90%, 7.50%, 10.54%, 7.63%, and 6.67%, respectively. The data of IQC practices indicated wide variation and substantial progress. The precision performance of cTnT was already satisfying, while the other five analytes, especially HCY, were still frustrating; thus, ongoing investigation and continuous improvement for IQC are still needed. © 2017 Wiley Periodicals, Inc.

Anesthetic-Induced Myocardial Preconditioning and Some Biochemical Markers for Cardiac and Coronary Failures after Aortocoronary Bypass Surgery

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V. V. Moroz

2013-01-01

Full Text Available Objective: to provide a rationale for the efficiency of sevoflurane-induced cardiac preconditioning (CPC, by assessing the pattern of recovery of heart rate and by estimating troponin I levels and changes in NT-proBNP concentrations in patients undergoing aortocoronary bypass surgery (ACBS under extracorporeal circulation (EC. Subjects and methods. Sixty patients aged 60.6±8 years (M±& were examined after elective ACBS using EC and divided into two groups of 30 patients each: 1 inhalation induction and maintenance of anesthesia (IIMA with sevoflurane and fentanyl, with CPC being simulated; 2 total intravenous anesthesia (TIA with propofol and fentanyl. Inhalation induction of sevoflurane anesthesia was performed in the IIMA group. Ten minutes before aortic ligation, the dose of the anesthetic was increased up to 2 MAC for CPC. Inhaled anesthetics were not used in the TIA group. The authors assessed the pattern of cardiac performance recovery and estimated the level of NT-proBNP 24 and 48 hours after tracheal intubation and that of troponin I following 24 hours of the intubation. Results. Defibrillation was required in one patient from the TIA group who developed ventricular fibrillation. The baseline levels of NT-proBNP were comparable in both groups. Following 24 hours, its level was more than thrice higher in the TIA group than that in the IIMA one (p<0.05. By the end of 2 days, the concentration of NT-proBNP continued to rise (up to 480% of the baseline level in the TIA group and returned to the preoperative values in the IIMA group (p=0.05. Twenty-four hours after tracheal intubation the level of troponin I was insignificantly higher in the TIA group than that in the IIMA group (p=0.1. Conclusion. Sevoflurane has cardioprotective properties in preventing and/or reducing the degree of heart failure after ACBS using EC. There is a need to continue the study in increased cohort to provide evidence that sevoflurane-induced CPC can lower

Role of Myofibril-Inducing RNA in cardiac TnT expression in developing Mexican axolotl

Science.gov (United States)

Sferrazza, Gian-Franco; Zhang, Chi; Jia, Pingping; Lemanski, Sharon L.; Athauda, Gagani; Stassi, Alyssa; Halager, Kristine; Maier, Jennifer A.; Rueda-de-Leon, Elena; Gupta, Amit; Dube, Syamalima; Huang, Xupei; Prentice, Howard M.; Dube, Dipak K.; Lemanski, Larry F.

2007-01-01

The Mexican axolotl, Ambystoma mexicanum, has been a useful animal model to study heart development and cardiac myofibrillogenesis. A naturally-occurring recessive mutant, gene “c”, for cardiac non-function in the Mexican axolotl causes a failure of myofibrillogenesis due to a lack of tropomyosin expression in homozygous mutant (c/c) embryonic hearts.. Myofibril-Inducing RNA (MIR) rescues mutant hearts in vitro by promoting tropomyosin expression and myofibril formation thereafter. We have studied the effect of MIR on the expression of various isoforms of cardiac Troponin-T (cTnT), a component of the thin filament that binds with tropomyosin. Four alternatively spliced cTnT isoforms have been characterized from developing axolotl heart. The expression of various cTnT isoforms in normal, mutant, and mutant hearts corrected with MIR, is evaluated by real-time RT-PCR using isoform specific primer pairs; MIR affects the total transcription as well as the splicing of the cTnT in axolotl heart PMID:17408593

Myocardial Injury in Patients With Sepsis and Its Association With Long-Term Outcome.

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Frencken, Jos F; Donker, Dirk W; Spitoni, Cristian; Koster-Brouwer, Marlies E; Soliman, Ivo W; Ong, David S Y; Horn, Janneke; van der Poll, Tom; van Klei, Wilton A; Bonten, Marc J M; Cremer, Olaf L

2018-02-01

Sepsis is frequently complicated by the release of cardiac troponin, but the clinical significance of this myocardial injury remains unclear. We studied the associations between troponin release during sepsis and 1-year outcomes. We enrolled consecutive patients with sepsis in 2 Dutch intensive care units between 2011 and 2013. Subjects with a clinically apparent cause of troponin release were excluded. High-sensitivity cardiac troponin I (hs-cTnI) concentration in plasma was measured daily during the first 4 intensive care unit days, and multivariable Cox regression analysis was used to model its association with 1-year mortality while adjusting for confounding. In addition, we studied cardiovascular morbidity occurring during the first year after hospital discharge. Among 1258 patients presenting with sepsis, 1124 (89%) were eligible for study inclusion. Hs-cTnI concentrations were elevated in 673 (60%) subjects on day 1, and 755 (67%) ever had elevated levels in the first 4 days. Cox regression analysis revealed that high hs-cTnI concentrations were associated with increased death rates during the first 14 days (adjusted hazard ratio, 1.72; 95% confidence interval, 1.14-2.59 and hazard ratio, 1.70; 95% confidence interval, 1.10-2.62 for hs-cTnI concentrations of 100-500 and >500 ng/L, respectively) but not thereafter. Furthermore, elevated hs-cTnI levels were associated with the development of cardiovascular disease among 200 hospital survivors who were analyzed for this end point (adjusted subdistribution hazard ratio, 1.25; 95% confidence interval, 1.04-1.50). Myocardial injury occurs in the majority of patients with sepsis and is independently associated with early-but not late-mortality, as well as postdischarge cardiovascular morbidity. © 2018 American Heart Association, Inc.

Resting spontaneous baroreflex sensitivity and cardiac autonomic control in anabolic androgenic steroid users

OpenAIRE

Santos, Marcelo R. dos; Sayegh, Ana L.C.; Armani, Rafael; Costa-Hong, Valéria; Souza, Francis R. de; Toschi-Dias, Edgar; Bortolotto, Luiz A.; Yonamine, Mauricio; Negrão, Carlos E.; Alves, Maria-Janieire N.N.

2018-01-01

OBJECTIVES: Misuse of anabolic androgenic steroids in athletes is a strategy used to enhance strength and skeletal muscle hypertrophy. However, its abuse leads to an imbalance in muscle sympathetic nerve activity, increased vascular resistance, and increased blood pressure. However, the mechanisms underlying these alterations are still unknown. Therefore, we tested whether anabolic androgenic steroids could impair resting baroreflex sensitivity and cardiac sympathovagal control. In addition, ...

Triptolide Upregulates Myocardial Forkhead Helix Transcription Factor p3 Expression and Attenuates Cardiac Hypertrophy

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Ding, Yuan-Yuan; Li, Jing-Mei; Guo, Feng-Jie; Liu, Ya; Tong, Yang-Fei; Pan, Xi-Chun; Lu, Xiao-Lan; Ye, Wen; Chen, Xiao-Hong; Zhang, Hai-Gang

2016-01-01

The forkhead/winged helix transcription factor (Fox) p3 can regulate the expression of various genes, and it has been reported that the transfer of Foxp3-positive T cells could ameliorate cardiac hypertrophy and fibrosis. Triptolide (TP) can elevate the expression of Foxp3, but its effects on cardiac hypertrophy remain unclear. In the present study, neonatal rat ventricular myocytes (NRVM) were isolated and stimulated with angiotensin II (1 μmol/L) to induce hypertrophic response. The expression of Foxp3 in NRVM was observed by using immunofluorescence assay. Fifty mice were randomly divided into five groups and received vehicle (control), isoproterenol (Iso, 5 mg/kg, s.c.), one of three doses of TP (10, 30, or 90 μg/kg, i.p.) for 14 days, respectively. The pathological morphology changes were observed after Hematoxylin and eosin, lectin and Masson’s trichrome staining. The levels of serum brain natriuretic peptide (BNP) and troponin I were determined by enzyme-linked immunosorbent assay and chemiluminescence, respectively. The mRNA and protein expressions of α- myosin heavy chain (MHC), β-MHC and Foxp3 were determined using real-time PCR and immunohistochemistry, respectively. It was shown that TP (1, 3, 10 μg/L) treatment significantly decreased cell size, mRNA and protein expression of β-MHC, and upregulated Foxp3 expression in NRVM. TP also decreased heart weight index, left ventricular weight index and, improved myocardial injury and fibrosis; and decreased the cross-scetional area of the myocardium, serum cardiac troponin and BNP. Additionally, TP markedly reduced the mRNA and protein expression of myocardial β-MHC and elevated the mRNA and protein expression of α-MHC and Foxp3 in a dose-dependent manner. In conclusion, TP can effectively ameliorate myocardial damage and inhibit cardiac hypertrophy, which is at least partly related to the elevation of Foxp3 expression in cardiomyocytes. PMID:27965581

Assessment of acute myocarditis by cardiac magnetic resonance imaging: Comparison of qualitative and quantitative analysis methods.

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Imbriaco, Massimo; Nappi, Carmela; Puglia, Marta; De Giorgi, Marco; Dell'Aversana, Serena; Cuocolo, Renato; Ponsiglione, Andrea; De Giorgi, Igino; Polito, Maria Vincenza; Klain, Michele; Piscione, Federico; Pace, Leonardo; Cuocolo, Alberto

2017-10-26

To compare cardiac magnetic resonance (CMR) qualitative and quantitative analysis methods for the noninvasive assessment of myocardial inflammation in patients with suspected acute myocarditis (AM). A total of 61 patients with suspected AM underwent coronary angiography and CMR. Qualitative analysis was performed applying Lake-Louise Criteria (LLC), followed by quantitative analysis based on the evaluation of edema ratio (ER) and global relative enhancement (RE). Diagnostic performance was assessed for each method by measuring the area under the curves (AUC) of the receiver operating characteristic analyses. The final diagnosis of AM was based on symptoms and signs suggestive of cardiac disease, evidence of myocardial injury as defined by electrocardiogram changes, elevated troponin I, exclusion of coronary artery disease by coronary angiography, and clinical and echocardiographic follow-up at 3 months after admission to the chest pain unit. In all patients, coronary angiography did not show significant coronary artery stenosis. Troponin I levels and creatine kinase were higher in patients with AM compared to those without (both P quantitative (ER 0.89 and global RE 0.80) analyses were also similar. Qualitative and quantitative CMR analysis methods show similar diagnostic accuracy for the diagnosis of AM. These findings suggest that a simplified approach using a shortened CMR protocol including only T2-weighted STIR sequences might be useful to rule out AM in patients with acute coronary syndrome and normal coronary angiography.

Impacto da troponina I cardíaca sérica na evolução tardia de pacientes submetidos a ressincronização com estimulação biventricular: seguimento de até 59 meses Impact of serum troponin I in the long-term evolution of patients submitted to resynchronization with biventricular stimulation: follow-up of up to 59 months

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João Carlos F. Leal

2005-09-01

, no deaths occurred and of the 8 patients with high levels, six died (p-value = 0.0003. The actuarial survival curve showed a survival rate of 47.1 ± 13.3% at the end of 59 months. CONCLUSION: VR in patients with CHF improves the QV and echocardiographic parameters (ejection fraction and LVDD. It is a good alternative for functional class III and IV patients. The serum levels of cardiac troponin I are predictors of risk to life.

Disease: H01730 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available emand of heart. Cardiovascular disease ... Old age Tobacco smoking High blood pressure High levels of LDL High cholesterol and fat Diab...etes Obesity Chronic kidney disease Alcohol Cocaine Amphetamines ... Cardiac troponin

Role of infarct location and pre-existing depression on cardiac baroreceptor sensitivity in subacute ischemic stroke

NARCIS (Netherlands)

De Vos, Aurelie; De Keyser, Jacques; De Raedt, Sylvie

Reduced cardiac baroreceptor sensitivity (BRS) after acute stroke is associated with worse outcome. The underlying mechanisms of reduced BRS are unclear. We evaluated cross correlation BRS (xBRS) in 184 patients with suspected acute ischemic stroke within 72 h of symptom onset. Among these patients,

Statin Intake Is Associated With Decreased Insulin Sensitivity During Cardiac Surgery

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Sato, Hiroaki; Carvalho, George; Sato, Tamaki; Hatzakorzian, Roupen; Lattermann, Ralph; Codere-Maruyama, Takumi; Matsukawa, Takashi; Schricker, Thomas

2012-01-01

OBJECTIVE Surgical trauma impairs intraoperative insulin sensitivity and is associated with postoperative adverse events. Recently, preprocedural statin therapy is recommended for patients with coronary artery disease. However, statin therapy is reported to increase insulin resistance and the risk of new-onset diabetes. Thus, we investigated the association between preoperative statin therapy and intraoperative insulin sensitivity in nondiabetic, dyslipidemic patients undergoing coronary artery bypass grafting. RESEARCH DESIGN AND METHODS In this prospective, nonrandomized trial, patients taking lipophilic statins were assigned to the statin group and hypercholesterolemic patients not receiving any statins were allocated to the control group. Insulin sensitivity was assessed by the hyperinsulinemic-normoglycemic clamp technique during surgery. The mean, SD of blood glucose, and the coefficient of variation (CV) after surgery were calculated for each patient. The association between statin use and intraoperative insulin sensitivity was tested by multiple regression analysis. RESULTS We studied 120 patients. In both groups, insulin sensitivity gradually decreased during surgery with values being on average ∼20% lower in the statin than in the control group. In the statin group, the mean blood glucose in the intensive care unit was higher than in the control group (153 ± 20 vs. 140 ± 20 mg/dL; P statin group (SD, P statin use was independently associated with intraoperative insulin sensitivity (β = −0.16; P = 0.03). CONCLUSIONS Preoperative use of lipophilic statins is associated with increased insulin resistance during cardiac surgery in nondiabetic, dyslipidemic patients. PMID:22829524

High-sensitivity C-reactive protein predicts target organ damage in Chinese patients with metabolic syndrome

DEFF Research Database (Denmark)

Zhao, Zhigang; Nie, Hai; He, Hongbo

2007-01-01

with metabolic syndrome. A total of 1082 consecutive patients of Chinese origin were screened for the presence of metabolic syndrome according to the National Cholesterol Education Program's Adult Treatment Panel III. High-sensitivity C-reactive protein and target organ damage, including cardiac hypertrophy......Observational studies established high-sensitivity C-reactive protein as a risk factor for cardiovascular events in the general population. The goal of this study was to determine the relationship between target organ damage and high-sensitivity C-reactive protein in a cohort of Chinese patients......, carotid intima-media thickness, and renal impairment, were investigated. The median (25th and 75th percentiles) of high-sensitivity C-reactive protein in 619 patients with metabolic syndrome was 2.42 mg/L (0.75 and 3.66 mg/L) compared with 1.13 mg/L (0.51 and 2.46 mg/L) among 463 control subjects (P

Nonexercise cardiac stress testing

International Nuclear Information System (INIS)

Vacek, J.L.; Baldwin, T.

1989-01-01

Many patients who require evaluation for coronary artery disease are unable to undergo exercise stress testing because of physiologic or psychological limitations. Drs Vacek and Baldwin describe three alternative methods for assessment of cardiac function in these patients, all of which have high levels of diagnostic sensitivity and specificity. 23 references

15. Sensitivity in visualizing vegetations in cardiac lead-induced endocarditis: A comparative study between transesophageal vs. transthoracic echocardiography

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A. AlFagih

2016-07-01

Full Text Available Despite advancement in sterile cardiac device implantation techniques, wound infections and/or bacteremia remain a significant problem. The presence of a vegetation in lead-induced endocarditis (LIE is a critical factor that determines the management. Transthoracic (TTE and Transesophageal (TEE Echocardiography are two different cardiac modalities that are used for the detection of lead vegetation. However, it is not yet clear which of the two has the highest diagnostic accuracy. We aim to identify which of the two has the highest sensitivity. In addition, we aim to correlate the existence of a vegetation with blood and wound culture results. We conducted a chart review in 113 patients whom underwent lead extraction at Prince Sultan Cardiac Center in Saudi Arabia during the period of Jan, 2002 to Jul, 2015. Six patients underwent lead extraction twice, increasing the number to be a total of 119 cases. Out of the study cohort, we include 38 patients who had both TTE and TEE done prior to lead extraction. Data regarding TTE, TEE, as well as blood and wound cultures were collected from echocardiography and microbiology lab reports using a well-structured case report form.Of the study population, 21 patients (55.3% had lead vegetations visualized either by TTE or TEE. Nineteen patients had vegetations detected by TEE, compared to 6 patients only when TTE was used. The sensitivity of TEE and TTE were 90.5% (CI: 69.6–98.8% and 28.5% (95% CI: 11.3–52.1%, respectively. Blood and wound culture results showed that in the presence of a vegetation, blood cultures were positive in 55% of the cases (P = 0.036 while only 44.4% of those with vegetations had a positive wound culture (P = 0.347. TEE has higher sensitivity in detecting vegetations compared to TTE in LIE. The presence of a vegetation is more likely to be associated with a positive blood culture than a positive wound culture. Further studies ought to measure the accuracy of different

E-1020, a water soluble imidazopyridine, has direct effects on Ca(2+)-dependent force and ATP hydrolysis of canine and bovine cardiac myofilaments.

Science.gov (United States)

Powers, F M; Palmiter, K A; Solaro, R J

1996-01-01

E-1020 is a cardiotonic agent that acts as a cyclic-AMP phosphodiesterase inhibitor but also may have actions which alter myofilament response to Ca2+. To identify direct actions of E-1020 on cardiac contractile proteins, effects of E-1020 on myofibrillar Ca2+ dependent MgATPase and force generation in chemically skinned fiber bundles were measured. In bovine cardiac myofibrils, E-1020 (100 microM) significantly increased myofilament Ca2+ sensitivity and Ca(2+)-dependent ATPase activity at submaximal pCa values. At pCa 6.75, E-1020 significantly increased ATPase activity in bovine (10-100 microM) and canine (1-100 microM) cardiac myofibrils but had no effect on rat cardiac myofibrils. Moreover, in one population of canine ventricular fiber bundles, E-1020 (0.01-10 microM) significantly increased isometric tension at pCa 6.5 and 6.0, whereas in another population of bundles E-1020 had no effect on tension. In no case was resting (pCa 8.0) or maximal tension (pCa 4.5) increased by E-1020. Measurements of Ca2+ binding to canine ventricular skinned fiber preparations demonstrated that E-1020 does not alter the affinity of myofilament troponin C for Ca2+. We conclude that part of the mechanism by which E-1020 acts as an inotropic agent may involve alterations in the responsiveness of contractile proteins to Ca2+. The lack of effect of E-1020 on some preparations may be dependent on isoform populations of myofilament proteins.

Imaging in cardiac mass lesions

International Nuclear Information System (INIS)

Mundinger, A.; Gruber, H.P.; Dinkel, E.; Geibel, A.; Beck, A.; Wimmer, B.; Schlosser, V.

1992-01-01

In 26 patients with cardiac mass lesions confirmed by surgery, diagnostic imaging was performed preoperatively by means of two-dimensional echocardiography (26 patients), angiography (12 patients), correlative computed tomography (CT, 8 patients), and magnetic resonance imaging (MRI, 3 patients). Two-dimensional echocardiography correctly identified the cardiac masses in all patients. Angiography missed two of 12 cardiac masses; CT missed one of eight. MRI identified three of three cardiac masses. Although the sensitivity of two-dimensional echocardiography was high (100%), all methods lacked specificity. None of the methods allowed differentiation between myxoma (n=13) and thrombus (n=7). Malignancy of the lesions was successfully predicted by noninvasive imaging methods in all six patients. However, CT and MRI provided additional information concerning cardiac mural infiltration, pericardial involvement, and extracardiac tumor extension, and should be integrated within a preoperative imaging strategy. Thus two-dimensional echocardiography is the method of choice for primary assessment of patients with suspected cardiac masses. Further preoperative imaging by CT or MRI can be limited to patients with malignancies suspected on the grounds of pericardial effusion or other clinical results. (author)

The Manchester Acute Coronary Syndromes (MACS) decision rule: validation with a new automated assay for heart-type fatty acid binding protein.

Science.gov (United States)

Body, Richard; Burrows, Gillian; Carley, Simon; Lewis, Philip S

2015-10-01

The Manchester Acute Coronary Syndromes (MACS) decision rule may enable acute coronary syndromes to be immediately 'ruled in' or 'ruled out' in the emergency department. The rule incorporates heart-type fatty acid binding protein (h-FABP) and high sensitivity troponin T levels. The rule was previously validated using a semiautomated h-FABP assay that was not practical for clinical implementation. We aimed to validate the rule with an automated h-FABP assay that could be used clinically. In this prospective diagnostic cohort study we included patients presenting to the emergency department with suspected cardiac chest pain. Serum drawn on arrival was tested for h-FABP using an automated immunoturbidimetric assay (Randox) and high sensitivity troponin T (Roche). The primary outcome, a diagnosis of acute myocardial infarction (AMI), was adjudicated based on 12 h troponin testing. A secondary outcome, major adverse cardiac events (MACE; death, AMI, revascularisation or new coronary stenosis), was determined at 30 days. Of the 456 patients included, 78 (17.1%) had AMI and 97 (21.3%) developed MACE. Using the automated h-FABP assay, the MACS rule had the same C-statistic for MACE as the original rule (0.91; 95% CI 0.88 to 0.92). 18.9% of patients were identified as 'very low risk' and thus eligible for immediate discharge with no missed AMIs and a 2.3% incidence of MACE (n=2, both coronary stenoses). 11.1% of patients were classed as 'high-risk' and had a 92.0% incidence of MACE. Our findings validate the performance of a refined MACS rule incorporating an automated h-FABP assay, facilitating use in clinical settings. The effectiveness of this refined rule should be verified in an interventional trial prior to implementation. UK CRN 8376. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Small-angle x-ray scattering investigation of the solution structure of troponin C

International Nuclear Information System (INIS)

Hubbard, S.R.; Hodgson, K.O.; Doniach, S.

1988-01-01

X-ray crystallographic studies of troponin C have revealed a novel protein structure consisting of two globular domains, each containing two Ca 2+ -binding sites, connected via a nine-turn alpha-helix, three turns of which are fully exposed to solvent. Since the crystals were grown at pH approximately 5, it is of interest to determine whether this structure is applicable to the protein in solution under physiological conditions. We have used small-angle x-ray scattering to examine the solution structure of troponin C at pH 6.8 and the effect of Ca 2+ on the structure. The scattering data are consistent with an elongated structure in solution with a radius of gyration of approximately 23.0 A, which is quite comparable to that computed for the crystal structure. The experimental scattering profile and the scattering profile computed from the crystal structure coordinates do, however, exhibit differences at the 40-A level. A weak Ca 2+ -facilitated dimerization of troponin C was observed. The data rule out large Ca 2+ -induced structural changes, indicating rather that the molecule with Ca 2+ bound is only slightly more compact than the Ca 2+ -free molecule

Circulating and Urinary miR-210 and miR-16 Increase during Cardiac Surgery Using Cardiopulmonary Bypass - A Pilot Study.

Science.gov (United States)

Mazzone, Annette L; Baker, Robert A; McNicholas, Kym; Woodman, Richard J; Michael, Michael Z; Gleadle, Jonathan M

2018-03-01

A pilot study to measure and compare blood and urine microRNAs miR-210 and miR-16 in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) and off-pump coronary artery bypass grafting surgery. Frequent serial blood and urine samples were taken from patients undergoing cardiac surgery with CPB (n = 10) and undergoing off-pump cardiac surgery (n = 5) before, during, and after surgery. Circulating miR-210 and miR-16 levels were determined by relative quantification real-time polymerase chain reaction. Levels of plasma-free haemoglobin (fHb), troponin-T, creatine kinase, and creatinine were measured. Perioperative serum miR-210 and miR-16 were elevated significantly compared to preoperative levels in patients undergoing cardiac surgery with CPB (CPB vs. Pre Op and Rewarm vs. Pre Op; p Octopus on vs. Pre Op); however, the release was less marked when compared to cardiac surgery with CPB. A significant association was observed between both miR-16 and miR-210 and plasma fHb when CPB was used ( r = -.549, p red cell, and renal injury during cardiac surgery.

Myofilament calcium sensitivity: Role in regulation of in vivo cardiac contraction and relaxation

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Jae-Hoon Chung

2016-12-01

Full Text Available Myofilament calcium sensitivity is an often-used indicator of cardiac muscle function, often assessed in disease states such as hypertrophic cardiomyopathy (HCM and dilated cardiomyopathy (DCM. While calcium sensitivity measurement provides important insights into the mechanical force-generating capability of a muscle at steady-state, the dynamic behavior of the muscle cannot be sufficiently assessed with a force-pCa curve alone. The dissociation constant (Kd of the force-pCa curve depends on the ratio of the apparent on-rate (kon and apparent off-rate (koff of calcium on TnC and as a stand-alone parameter cannot provide an accurate depiction of the dynamic contraction and relaxation behavior without the additional quantification of kon or koff, or actually measuring dynamic twitch kinetics in an intact muscle. In this review, we examine the effect of length, frequency, and beta-adrenergic stimulation on myofilament calcium sensitivity and dynamic contraction, the effect of membrane permeabilization on calcium sensitivity, and the dynamic consequences of various myofilament protein mutations with potential implications in contractile and relaxation behavior.

Dynamic adaptation of cardiac baroreflex sensitivity to prolonged exposure to microgravity: data from a 16-day spaceflight

NARCIS (Netherlands)

Di Rienzo, Marco; Castiglioni, Paolo; Iellamo, Ferdinando; Volterrani, Maurizio; Pagani, Massimo; Mancia, Giuseppe; Karemaker, John M.; Parati, Gianfranco

2008-01-01

Di Rienzo M, Castiglioni P, Iellamo F, Volterrani M, Pagani M, Mancia G, Karemaker JM, Parati G. Dynamic adaptation of cardiac baroreflex sensitivity to prolonged exposure to microgravity: data from a 16-day spaceflight. J Appl Physiol 105: 1569-1575, 2008. First published August 28, 2008;

Coronary Artery-Bypass-Graft Surgery Increases the Plasma Concentration of Exosomes Carrying a Cargo of Cardiac MicroRNAs: An Example of Exosome Trafficking Out of the Human Heart with Potential for Cardiac Biomarker Discovery.

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Costanza Emanueli

Full Text Available Exosome nanoparticles carry a composite cargo, including microRNAs (miRs. Cultured cardiovascular cells release miR-containing exosomes. The exosomal trafficking of miRNAs from the heart is largely unexplored. Working on clinical samples from coronary-artery by-pass graft (CABG surgery, we investigated if: 1 exosomes containing cardiac miRs and hence putatively released by cardiac cells increase in the circulation after surgery; 2 circulating exosomes and exosomal cardiac miRs correlate with cardiac troponin (cTn, the current "gold standard" surrogate biomarker of myocardial damage.The concentration of exosome-sized nanoparticles was determined in serial plasma samples. Cardiac-expressed (miR-1, miR-24, miR-133a/b, miR-208a/b, miR-210, non-cardiovascular (miR-122 and quality control miRs were measured in whole plasma and in plasma exosomes. Linear regression analyses were employed to establish the extent to which the circulating individual miRs, exosomes and exosomal cardiac miR correlated with cTn-I. Cardiac-expressed miRs and the nanoparticle number increased in the plasma on completion of surgery for up to 48 hours. The exosomal concentration of cardiac miRs also increased after CABG. Cardiac miRs in the whole plasma did not correlate significantly with cTn-I. By contrast cTn-I was positively correlated with the plasma exosome level and the exosomal cardiac miRs.The plasma concentrations of exosomes and their cargo of cardiac miRs increased in patients undergoing CABG and were positively correlated with hs-cTnI. These data provide evidence that CABG induces the trafficking of exosomes from the heart to the peripheral circulation. Future studies are necessary to investigate the potential of circulating exosomes as clinical biomarkers in cardiac patients.

Frequency of cardiac arrhythmias in high and low- yielding dairy cows

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Afshin Jafari Dehkordi

2014-06-01

Full Text Available Electrocardiography (ECG may be used to recognize cardiac disorders. Levels of milk production may change the serum electrolytes which its imbalance has a role in cardiac arrhythmia. Fifty high yielding and fifty low yielding Holstein dairy cows were used in this study. Electrocardiography was recorded by base-apex lead and blood samples were collected from jugular vein for measurement of serum elements such as sodium, potassium, calcium, phosphorous, iron and magnesium. Cardiac dysrhythmias were detected more frequent in low yielding Holstein cows (62.00% compared to high yielding Holstein cows (46.00%. The cardiac dysrhythmias that were observed in low yielding Holstein cows included sinus arrhythmia (34.70%, wandering pacemaker (22.45 %, bradycardia (18.37%, tachycardia (10.20%, atrial premature beat (2.04%, sinoatrial block (2.04%, atrial fibrillation (8.16% and atrial tachycardia (2.04%. The cardiac dysrhythmias were observed in high yielding Holstein cows including, sinus arrhythmia (86.95% and wandering pacemaker (13.05%. Also, notched P wave was observed to be 30% and 14% in high- and low- yielding Holstein cows respectively. The serum calcium concentration of low yielding Holstein cows was significantly lower than that of high yielding Holstein cows. There was not any detectable significant difference in other serum elements between high- and low- yielding Holstein cows. Based on the result of present study, could be concluded that low serum concentration of calcium results to more frequent dysrhythmias in low yielding Holstein cows.

The effect of space microgravity on the physiological activity of mammalian resident cardiac stem cells

Science.gov (United States)

Belostotskaya, Galina; Zakharov, Eugeny

Prolonged exposure to weightlessness during space flights is known to cause depression of heart function in mammals. The decrease in heart weight and its remodeling under the influence of prolonged weightlessness (or space microgravity) is assumed to be due to both morphological changes of working cardiomyocytes and their progressive loss, as well as to possible depletion of resident cardiac stem cells (CSCs) population, or their inability to self-renewal and regeneration of muscle tissue under conditions of weightlessness. We have previously shown that the presence of different maturity clones formed by resident CSCs not only in culture but also in the mammalian myocardium can be used as an indicator of the regenerative activity of myocardial cells [Belostotskaya, et al., 2013: 2014]. In this study, we were interested to investigate whether the 30-day near-Earth space flight on the spacecraft BION-M1 affects the regenerative potential of resident CSCs. Immediately after landing of the spacecraft, we had examined the presence of resident c-kit+, Sca-1+ and Isl1+ CSCs and their development in suspension of freshly isolated myocardial cells of C57BL mice in comparison to controls. Cardiac cell suspension was obtained by enzymatic digestion of the heart [Belostotskaya and Golovanova, 2014]. Immunocytochemically stained preparations of fixed cells were analyzed with confocal microscope Leica TCS SP5 (Germany) in the Resource Center of St-Petersburg State University. CSCs were labeled with appropriate antibodies. CSCs differentiation into mature cardiomyocytes was verified using antibodies to Sarcomeric α-Actinin and Cardiac Troponin T. Antibodies to Connexin43 were used to detect cell-cell contacts. All antibodies were conjugated with Alexa fluorochromes (488, 532, 546, 568, 594 and/or 647 nm), according to Zenon-technology (Invitrogen). It has been shown that, under identical conditions of cell isolation, more complete digestion of heart muscle was observed in

An algorithm for rule-in and rule-out of acute myocardial infarction using a novel troponin I assay.

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Lindahl, Bertil; Jernberg, Tomas; Badertscher, Patrick; Boeddinghaus, Jasper; Eggers, Kai M; Frick, Mats; Rubini Gimenez, Maria; Linder, Rickard; Ljung, Lina; Martinsson, Arne; Melki, Dina; Nestelberger, Thomas; Rentsch, Katharina; Reichlin, Tobias; Sabti, Zaid; Schubera, Marie; Svensson, Per; Twerenbold, Raphael; Wildi, Karin; Mueller, Christian

2017-01-15

To derive and validate a hybrid algorithm for rule-out and rule-in of acute myocardial infarction based on measurements at presentation and after 2 hours with a novel cardiac troponin I (cTnI) assay. The algorithm was derived and validated in two cohorts (605 and 592 patients) from multicentre studies enrolling chest pain patients presenting to the emergency department (ED) with onset of last episode within 12 hours. The index diagnosis and cardiovascular events up to 30 days were adjudicated by independent reviewers. In the validation cohort, 32.6% of the patients were ruled out on ED presentation, 6.1% were ruled in and 61.3% remained undetermined. A further 22% could be ruled out and 9.8% ruled in, after 2 hours. In total, 54.6% of the patients were ruled out with a negative predictive value (NPV) of 99.4% (95% CI 97.8% to 99.9%) and a sensitivity of 97.7% (95% CI 91.9% to 99.7%); 15.8% were ruled in with a positive predictive value (PPV) of 74.5% (95% CI 64.8% to 82.2%) and a specificity of 95.2% (95% CI 93.0% to 96.9%); and 29.6% remained undetermined after 2 hours. No patient in the rule-out group died during the 30-day follow-up in the two cohorts. This novel two-step algorithm based on cTnI measurements enabled just over a third of the patients with acute chest pain to be ruled in or ruled out already at presentation and an additional third after 2 hours. This strategy maximises the speed of rule-out and rule-in while maintaining a high NPV and PPV, respectively. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

A randomized controlled trial of levosimendan to reduce mortality in high-risk cardiac surgery patients (CHEETAH): Rationale and design.

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Zangrillo, Alberto; Alvaro, Gabriele; Pisano, Antonio; Guarracino, Fabio; Lobreglio, Rosetta; Bradic, Nikola; Lembo, Rosalba; Gianni, Stefano; Calabrò, Maria Grazia; Likhvantsev, Valery; Grigoryev, Evgeny; Buscaglia, Giuseppe; Pala, Giovanni; Auci, Elisabetta; Amantea, Bruno; Monaco, Fabrizio; De Vuono, Giovanni; Corcione, Antonio; Galdieri, Nicola; Cariello, Claudia; Bove, Tiziana; Fominskiy, Evgeny; Auriemma, Stefano; Baiocchi, Massimo; Bianchi, Alessandro; Frontini, Mario; Paternoster, Gianluca; Sangalli, Fabio; Wang, Chew-Yin; Zucchetti, Maria Chiara; Biondi-Zoccai, Giuseppe; Gemma, Marco; Lipinski, Michael J; Lomivorotov, Vladimir V; Landoni, Giovanni

2016-07-01

Patients undergoing cardiac surgery are at risk of perioperative low cardiac output syndrome due to postoperative myocardial dysfunction. Myocardial dysfunction in patients undergoing cardiac surgery is a potential indication for the use of levosimendan, a calcium sensitizer with 3 beneficial cardiovascular effects (inotropic, vasodilatory, and anti-inflammatory), which appears effective in improving clinically relevant outcomes. Double-blind, placebo-controlled, multicenter randomized trial. Tertiary care hospitals. Cardiac surgery patients (n = 1,000) with postoperative myocardial dysfunction (defined as patients with intraaortic balloon pump and/or high-dose standard inotropic support) will be randomized to receive a continuous infusion of either levosimendan (0.05-0.2 μg/[kg min]) or placebo for 24-48 hours. The primary end point will be 30-day mortality. Secondary end points will be mortality at 1 year, time on mechanical ventilation, acute kidney injury, decision to stop the study drug due to adverse events or to start open-label levosimendan, and length of intensive care unit and hospital stay. We will test the hypothesis that levosimendan reduces 30-day mortality in cardiac surgery patients with postoperative myocardial dysfunction. This trial is planned to determine whether levosimendan could improve survival in patients with postoperative low cardiac output syndrome. The results of this double-blind, placebo-controlled randomized trial may provide important insights into the management of low cardiac output in cardiac surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

Predictive role of stress echocardiography before carotid endarterectomy in patients with coronary artery disease.

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Galyfos, George; Tsioufis, Constantinos; Theodorou, Dimitris; Katsaragakis, Stilianos; Zografos, Georgios; Filis, Konstantinos

2015-07-01

Our aim was to examine the predictive value of preoperative stress echocardiography regarding early myocardial ischemia and late cardiac events after carotid endarterectomy (CEA). Patients with coronary artery disease undergoing CEA were prospectively included in this study. All patients (n = 162) were classified into low, medium, and high cardiac risk group, according to preoperative stress echocardiography. Classification was based on the criteria of the American Society of Echocardiography. For all patients, cTnI was measured before surgery and on postoperative days 1, 3, and 7. Postoperative cTnI values ranging from 0.05 to 0.5 ng/mL were classified as myocardial ischemia; values >0.5 ng/mL were classified as myocardial infarction. Cardiac damage was defined as either myocardial ischemia or infarction. No deaths, strokes, or symptomatic coronary events were observed during the early postoperative period. There were 112 low cardiac risk patients, 42 medium-risk patients, and 8 high-risk patients, according to stress echocardiography findings. Overall, there were 22 patients (14%) that increased their cTnI values postoperatively (12 of low cardiac risk and 10 of medium cardiac risk), and all of them were asymptomatic. None of the high-risk patients showed any troponin increase. Late cardiac events were associated with cTnI increase, although no high-risk patients showed any late event. Preoperative stress echocardiography does not seem to independently recognize patients in high risk for asymptomatic cardiac damage after CEA. Postoperative troponin elevation seems to be more predictive for late adverse cardiac events than preoperative stress echocardiography. © 2014, Wiley Periodicals, Inc.

New cardiac cameras: single-photon emission CT and PET.

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Slomka, Piotr J; Berman, Daniel S; Germano, Guido

2014-07-01

Nuclear cardiology instrumentation has evolved significantly in the recent years. Concerns about radiation dose and long acquisition times have propelled developments of dedicated high-efficiency cardiac SPECT scanners. Novel collimator designs, such as multipinhole or locally focusing collimators arranged in geometries that are optimized for cardiac imaging, have been implemented to enhance photon-detection sensitivity. Some of these new SPECT scanners use solid-state photon detectors instead of photomultipliers to improve image quality and to reduce the scanner footprint. These new SPECT devices allow dramatic up to 7-fold reduction in acquisition times or similar reduction in radiation dose. In addition, new hardware for photon attenuation correction allowing ultralow radiation doses has been offered by some vendors. To mitigate photon attenuation artifacts for the new SPECT scanners not equipped with attenuation correction hardware, 2-position (upright-supine or prone-supine) imaging has been proposed. PET hardware developments have been primarily driven by the requirements of oncologic imaging, but cardiac imaging can benefit from improved PET image quality and improved sensitivity of 3D systems. The time-of-flight reconstruction combined with resolution recovery techniques is now implemented by all major PET vendors. These new methods improve image contrast and image resolution and reduce image noise. High-sensitivity 3D PET without interplane septa allows reduced radiation dose for cardiac perfusion imaging. Simultaneous PET/MR hybrid system has been developed. Solid-state PET detectors with avalanche photodiodes or digital silicon photomultipliers have been introduced, and they offer improved imaging characteristics and reduced sensitivity to electromagnetic MR fields. Higher maximum count rate of the new PET detectors allows routine first-pass Rb-82 imaging, with 3D PET acquisition enabling clinical utilization of dynamic imaging with myocardial flow

Clinical and Prognostic Profiles of Cardiomyopathies Caused by Mutations in the Troponin T Gene.

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Ripoll-Vera, Tomás; Gámez, José María; Govea, Nancy; Gómez, Yolanda; Núñez, Juana; Socías, Lorenzo; Escandell, Ángela; Rosell, Jorge

2016-02-01

Mutations in the troponin T gene (TTNT2) have been associated in small studies with the development of hypertrophic cardiomyopathy characterized by a high risk of sudden death and mild hypertrophy. We describe the clinical course of patients carrying mutations in this gene. We analyzed the clinical characteristics and prognosis of patients with mutations in the TNNT2 gene who were seen in an inherited cardiac disease unit. Of 180 families with genetically studied cardiomyopathies, 21 families (11.7%) were identified as having mutations in TNNT2: 10 families had Arg92Gln, 5 had Arg286His, 3 had Arg278Cys, 1 had Arg92Trp, 1 had Arg94His, and 1 had Ile221Thr. Thirty-three additional genetic carriers were identified through family assessment. The study included 54 genetic carriers: 56% were male, and the mean average age was 41 ± 17 years. There were 33 cases of hypertrophic cardiomyopathy, 9 of dilated cardiomyopathy, and 1 of noncompaction cardiomyopathy, and maximal myocardial thickness was 18.5 ± 6mm. Ventricular dysfunction was present in 30% of individuals and a history of sudden death in 62%. During follow-up, 4 patients died and 14 (33%) received a defibrillator (8 probands, 6 relatives). Mean survival was 54 years. Carriers of Arg92Gln had early disease development, high penetrance, a high risk of sudden death, a high rate of defibrillator implantation, and a high frequency of mixed phenotype. Mutations in the TNNT2 gene were more common in this series than in previous studies. The clinical and prognostic profiles depended on the mutation present. Carriers of the Arg92Gln mutation developed hypertrophic or dilated cardiomyopathy and had a significantly worse prognosis than those with other mutations in TNNT2 or other sarcomeric genes. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Pre-Clinical Tests of an Integrated CMOS Biomolecular Sensor for Cardiac Diseases Diagnosis.

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Lee, Jen-Kuang; Wang, I-Shun; Huang, Chi-Hsien; Chen, Yih-Fan; Huang, Nien-Tsu; Lin, Chih-Ting

2017-11-26

Coronary artery disease and its related complications pose great threats to human health. In this work, we aim to clinically evaluate a CMOS field-effect biomolecular sensor for cardiac biomarkers, cardiac-specific troponin-I (cTnI), N -terminal prohormone brain natriuretic peptide (NT-proBNP), and interleukin-6 (IL-6). The CMOS biosensor is implemented via a standard commercialized 0.35 μm CMOS process. To validate the sensing characteristics, in buffer conditions, the developed CMOS biosensor has identified the detection limits of IL-6, cTnI, and NT-proBNP as being 45 pM, 32 pM, and 32 pM, respectively. In clinical serum conditions, furthermore, the developed CMOS biosensor performs a good correlation with an enzyme-linked immuno-sorbent assay (ELISA) obtained from a hospital central laboratory. Based on this work, the CMOS field-effect biosensor poses good potential for accomplishing the needs of a point-of-care testing (POCT) system for heart disease diagnosis.

Incidence of myocardial injury after noncardiac surgery: Experience at Groote Schuur Hospital Cape Town South Africa

Directory of Open Access Journals (Sweden)

R Dyer

2018-04-01

Full Text Available Background. Myocardial injury after non-cardiac surgery (MINS is a newly recognised entity identified as an independent risk factor associated with increased 30-day all-cause mortality. MINS increases the risk of death in the perioperative period by ~10-fold. More than 80% of patients with MINS are asymptomatic, so the majority of diagnoses are missed. Awareness of MINS is therefore important for perioperative physicians.Objectives. To investigate the incidence of MINS after elective elevated-risk non-cardiac surgery at Groote Schuur Hospital, Cape Town, South Africa (SA.Methods. Patients aged ≥45 years undergoing elective elevated-risk non-cardiac surgery were enrolled via convenience sampling. The new fifth-generation high-sensitivity cardiac troponin T blood test was used postoperatively to identify MINS. Preoperative troponin levels were not measured.Results. Among 244 patients included in the study, the incidence of MINS was 4.9% (95% confidence interval (CI 2.8 - 8.5, which was not significantly different from that in a major international prospective observational study (VISION (8.0% (95% CI 7.5 - 8.4; p=0.080.Conclusions. Our SA cohort had a lower cardiovascular risk profile but a similar incidence of MINS to that described in international literature. The impact of MINS on morbidity and mortality is therefore likely to be proportionally higher in SA than in published international studies. The limited sample size and lower event rate weaken our conclusions. Larger studies are required to establish patient and surgical risk factors for MINS, allowing for revision of cardiovascular risk prediction models in SA. 

Estimated Aortic Stiffness is Independently Associated with Cardiac Baroreflex Sensitivity in Humans: Role of Aging and Habitual Endurance Exercise

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Pierce, Gary L.; Harris, Stephen A.; Seals, Douglas R.; Casey, Darren P.; Barlow, Patrick B.; Stauss, Harald M.

2016-01-01

We hypothesized that differences in cardiac baroreflex sensitivity (BRS) would be independently associated with aortic stiffness and augmentation index (AI), clinical biomarkers of cardiovascular disease (CVD) risk, among young sedentary and middle-aged/older sedentary and endurance-trained adults. A total of 36 healthy middle-aged/older (age 55-76 years, n=22 sedentary; n=14 endurance-trained) and 5 young sedentary (age 18-31 years) adults were included in a cross-sectional study. A subset of the middle-aged/older sedentary adults (n=12) completed an 8-week aerobic exercise intervention. Invasive brachial artery blood pressure waveforms were used to compute spontaneous cardiac BRS (via sequence technique) and estimated aortic pulse wave velocity (PWV) and AI (AI, via brachial-aortic transfer function and wave separation analysis). In the cross-sectional study, cardiac BRS was 71% lower in older compared with young sedentary adults (Pendurance exercise (P=0.03). In a regression model that included age, sex, resting heart rate, mean arterial pressure (MAP), body mass index and maximal exercise oxygen uptake, estimated aortic PWV (β±SE = −5.76 ± 2.01, P=0.01) was the strongest predictor of BRS (Model R2=0.59, Pendurance exercise-related differences in cardiac BRS are independently associated with corresponding alterations in aortic PWV among healthy adults, consistent with a mechanistic link between variations in the sensitivity of the baroreflex and aortic stiffness with age and exercise. PMID:26911535

Estimated aortic stiffness is independently associated with cardiac baroreflex sensitivity in humans: role of ageing and habitual endurance exercise.

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Pierce, G L; Harris, S A; Seals, D R; Casey, D P; Barlow, P B; Stauss, H M

2016-09-01

We hypothesised that differences in cardiac baroreflex sensitivity (BRS) would be independently associated with aortic stiffness and augmentation index (AI), clinical biomarkers of cardiovascular disease risk, among young sedentary and middle-aged/older sedentary and endurance-trained adults. A total of 36 healthy middle-aged/older (age 55-76 years, n=22 sedentary and n=14 endurance-trained) and 5 young sedentary (age 18-31 years) adults were included in a cross-sectional study. A subset of the middle-aged/older sedentary adults (n=12) completed an 8-week-aerobic exercise intervention. Invasive brachial artery blood pressure waveforms were used to compute spontaneous cardiac BRS (via sequence technique), estimated aortic pulse wave velocity (PWV) and AI (AI, via brachial-aortic transfer function and wave separation analysis). In the cross-sectional study, cardiac BRS was 71% lower in older compared with young sedentary adults (Pendurance exercise (P=0.03). In a regression model that included age, sex, resting heart rate, mean arterial pressure (MAP), body mass index and maximal exercise oxygen uptake, estimated aortic PWV (β±s.e.=-5.76±2.01, P=0.01) was the strongest predictor of BRS (model R(2)=0.59, Pendurance-exercise-related differences in cardiac BRS are independently associated with corresponding alterations in aortic PWV among healthy adults, consistent with a mechanistic link between variations in the sensitivity of the baroreflex and aortic stiffness with age and exercise.

Assessment and treatment of post patent ductus arteriosus ligation syndrome.

LENUS (Irish Health Repository)

El-Khuffash, Afif F

2014-07-01

To compare differences in tissue Doppler imaging, global longitudinal strain (GLS), and cardiac troponin T (cTnT) between infants with low (<200 mL\\/kg\\/min) and high (>200 mL\\/kg\\/min) left ventricular (LV) output 1 hour after duct ligation and assess the impact of milrinone treatment on cardiac output and myocardial performance.

Depressed Frank-Starling mechanism in the left ventricular muscle of the knock-in mouse model of dilated cardiomyopathy with troponin T deletion mutation ΔK210.

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Inoue, Takahiro; Kobirumaki-Shimozawa, Fuyu; Kagemoto, Tatsuya; Fujii, Teruyuki; Terui, Takako; Kusakari, Yoichiro; Hongo, Kenichi; Morimoto, Sachio; Ohtsuki, Iwao; Hashimoto, Kazuhiro; Fukuda, Norio

2013-10-01

It has been reported that the Frank-Starling mechanism is coordinately regulated in cardiac muscle via thin filament "on-off" equilibrium and titin-based lattice spacing changes. In the present study, we tested the hypothesis that the deletion mutation ΔK210 in the cardiac troponin T gene shifts the equilibrium toward the "off" state and accordingly attenuate the sarcomere length (SL) dependence of active force production, via reduced cross-bridge formation. Confocal imaging in isolated hearts revealed that the cardiomyocytes were enlarged, especially in the longitudinal direction, in ΔK210 hearts, with striation patterns similar to those in wild type (WT) hearts, suggesting that the number of sarcomeres is increased in cardiomyocytes but the sarcomere length remains unaltered. For analysis of the SL dependence of active force, skinned muscle preparations were obtained from the left ventricle of WT and knock-in (ΔK210) mice. An increase in SL from 1.90 to 2.20μm shifted the mid-point (pCa50) of the force-pCa curve leftward by ~0.21pCa units in WT preparations. In ΔK210 muscles, Ca(2+) sensitivity was lower by ~0.37pCa units, and the SL-dependent shift of pCa50, i.e., ΔpCa50, was less pronounced (~0.11pCa units), with and without protein kinase A treatment. The rate of active force redevelopment was lower in ΔK210 preparations than in WT preparations, showing blunted thin filament cooperative activation. An increase in thin filament cooperative activation upon an increase in the fraction of strongly bound cross-bridges by MgADP increased ΔpCa50 to ~0.21pCa units. The depressed Frank-Starling mechanism in ΔK210 hearts is the result of a reduction in thin filament cooperative activation. © 2013.

Risk stratification in non-ST elevation acute coronary syndromes: Risk scores, biomarkers and clinical judgment

Directory of Open Access Journals (Sweden)

David Corcoran

2015-09-01

Clinical guidelines recommend an early invasive strategy in higher risk NSTE-ACS. The Global Registry of Acute Coronary Events (GRACE risk score is a validated risk stratification tool which has incremental prognostic value for risk stratification compared with clinical assessment or troponin testing alone. In emergency medicine, there has been a limited adoption of the GRACE score in some countries (e.g. United Kingdom, in part related to a delay in obtaining timely blood biochemistry results. Age makes an exponential contribution to the GRACE score, and on an individual patient basis, the risk of younger patients with a flow-limiting culprit coronary artery lesion may be underestimated. The future incorporation of novel cardiac biomarkers into this diagnostic pathway may allow for earlier treatment stratification. The cost-effectiveness of the new diagnostic pathways based on high-sensitivity troponin and copeptin must also be established. Finally, diagnostic tests and risk scores may optimize patient care but they cannot replace patient-focused good clinical judgment.

Changes in cardiac and muscle biomarkers following an uphill-only marathon.

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Da Ponte, Alessandro; Giovanelli, Nicola; Antonutto, Guglielmo; Nigris, Daniele; Curcio, Francesco; Cortese, Pietro; Lazzer, Stefano

2018-01-01

The aim of the study was to evaluate changes in cardiac troponin I levels (cTnI) and the main biomarkers of skeletal muscle damage after an uphill-only marathon, along with its relationship with athletes' physiological parameters. Twenty-two runners participated in the "Supermaratona dell'Etna" (43 km, 0-2850 m AMSL). Before and immediately after the race, body mass and hydration status were measured together with blood sampling. At the end of the race, mean cTnI increased significantly in all athletes (mean +900%), and in 52% of them the cTnI values were over the normal range. Mean creatinine and cortisol increased significantly (by 30.5% and 291.4%), while C-reactive protein levels did not change significantly. Then, an uphill-only marathon showed a significant increase in cardiac and skeletal muscle blood biomarkers of injury, and cTnI levels were not significantly correlated with age, body mass index, V̇O 2 max, training status, ultra-endurance training experience, race time and blood parameters.

Mast cells regulate myofilament calcium sensitization and heart function after myocardial infarction.

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Ngkelo, Anta; Richart, Adèle; Kirk, Jonathan A; Bonnin, Philippe; Vilar, Jose; Lemitre, Mathilde; Marck, Pauline; Branchereau, Maxime; Le Gall, Sylvain; Renault, Nisa; Guerin, Coralie; Ranek, Mark J; Kervadec, Anaïs; Danelli, Luca; Gautier, Gregory; Blank, Ulrich; Launay, Pierre; Camerer, Eric; Bruneval, Patrick; Menasche, Philippe; Heymes, Christophe; Luche, Elodie; Casteilla, Louis; Cousin, Béatrice; Rodewald, Hans-Reimer; Kass, David A; Silvestre, Jean-Sébastien

2016-06-27

Acute myocardial infarction (MI) is a severe ischemic disease responsible for heart failure and sudden death. Inflammatory cells orchestrate postischemic cardiac remodeling after MI. Studies using mice with defective mast/stem cell growth factor receptor c-Kit have suggested key roles for mast cells (MCs) in postischemic cardiac remodeling. Because c-Kit mutations affect multiple cell types of both immune and nonimmune origin, we addressed the impact of MCs on cardiac function after MI, using the c-Kit-independent MC-deficient (Cpa3(Cre/+)) mice. In response to MI, MC progenitors originated primarily from white adipose tissue, infiltrated the heart, and differentiated into mature MCs. MC deficiency led to reduced postischemic cardiac function and depressed cardiomyocyte contractility caused by myofilament Ca(2+) desensitization. This effect correlated with increased protein kinase A (PKA) activity and hyperphosphorylation of its targets, troponin I and myosin-binding protein C. MC-specific tryptase was identified to regulate PKA activity in cardiomyocytes via protease-activated receptor 2 proteolysis. This work reveals a novel function for cardiac MCs modulating cardiomyocyte contractility via alteration of PKA-regulated force-Ca(2+) interactions in response to MI. Identification of this MC-cardiomyocyte cross-talk provides new insights on the cellular and molecular mechanisms regulating the cardiac contractile machinery and a novel platform for therapeutically addressable regulators. ©2016 Ngkelo et al.

Myocardial scaffold-based cardiac tissue engineering: application of coordinated mechanical and electrical stimulations.

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Wang, Bo; Wang, Guangjun; To, Filip; Butler, J Ryan; Claude, Andrew; McLaughlin, Ronald M; Williams, Lakiesha N; de Jongh Curry, Amy L; Liao, Jun

2013-09-03

Recently, we developed an optimal decellularization protocol to generate 3D porcine myocardial scaffolds, which preserve the natural extracellular matrix structure, mechanical anisotropy, and vasculature templates and also show good cell recellularization and differentiation potential. In this study, a multistimulation bioreactor was built to provide coordinated mechanical and electrical stimulation for facilitating stem cell differentiation and cardiac construct development. The acellular myocardial scaffolds were seeded with mesenchymal stem cells (10(6) cells/mL) by needle injection and subjected to 5-azacytidine treatment (3 μmol/L, 24 h) and various bioreactor conditioning protocols. We found that after 2 days of culturing with mechanical (20% strain) and electrical stimulation (5 V, 1 Hz), high cell density and good cell viability were observed in the reseeded scaffold. Immunofluorescence staining demonstrated that the differentiated cells showed a cardiomyocyte-like phenotype by expressing sarcomeric α-actinin, myosin heavy chain, cardiac troponin T, connexin-43, and N-cadherin. Biaxial mechanical testing demonstrated that positive tissue remodeling took place after 2 days of bioreactor conditioning (20% strain + 5 V, 1 Hz); passive mechanical properties of the 2 day and 4 day tissue constructs were comparable to those of the tissue constructs produced by stirring reseeding followed by 2 weeks of static culturing, implying the effectiveness and efficiency of the coordinated simulations in promoting tissue remodeling. In short, the synergistic stimulations might be beneficial not only for the quality of cardiac construct development but also for patients by reducing the waiting time in future clinical scenarios.

Myocarditis with ST elevation and elevated cardiac enzymes misdiagnosed as an ST-elevation myocardial infarction.

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Sheldon, Seth H; Crandall, Mark A; Jaffe, Allan S

2012-12-01

Acute myocarditis can mimic ST-elevation myocardial infarction (STEMI). Quickly determining the correct diagnosis is critical given the "time is muscle" implication with a STEMI and the potential adverse effects associated with use of fibrinolytic therapy. A 46-year-old man presented to a rural emergency department with chest pain, and an electrocardiogram (ECG) read as showing 0.1 mV of ST-segment elevation in leads III and aVF. His initial cardiac troponin T was 0.44 ng/mL. He received fibrinolytic therapy for presumed STEMI. Cardiac magnetic resonance imaging was later performed and showed epicardial delayed enhancement consistent with myocarditis. Upon further questioning, he acknowledged 3 days of stuttering chest discomfort and a recent upper respiratory infection, as well as similar chest pain in his wife. A systematic evaluation is essential for acute chest pain, including a focused history, identification of cardiac risk factors, and ECG interpretation. A history of recent viral illness, absence of cardiac risk factors, or ECG findings inconsistent with a single anatomic lesion would suggest a potential alternate diagnosis to STEMI. This case emphasizes the importance of a focused history in the initial evaluation of chest pain. Copyright © 2012 Elsevier Inc. All rights reserved.

Changes in the level of cardiac troponine and disorders in pulmonary gas exchange as predictors of short- and long-term outcomes of patients with aneurysm subarachnoid haemorrhage.

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Burzyńska, Małgorzata; Uryga, Agnieszka; Kasprowicz, Magdalena; Kędziora, Jarosław; Szewczyk, Ewa; Woźniak, Jowita; Jarmundowicz, Włodzimierz; Kübler, Andrzej

2017-12-01

Cardiopulmonary abnormalities are common after aneurysmal subarachnoid haemorrhage (aSAH). However, the relationship between short- and long-term outcome is poorly understood. In this paper, we present how cardiac troponine elevations (cTnI) and pulmonary disorders are associated with short- and long-term outcomes assessed by the Glasgow Outcome Scale (GOS) and Extended Glasgow Outcome Scale (GOSE). A total of 104 patients diagnosed with aSAH were analysed in the study. The non-parametric U Mann-Whitney test was used to evaluate the difference between good (GOS IV-V, GOSE V-VIII) and poor (GOS I-III, GOSE I-IV) outcomes in relation to cTnI elevation and pulmonary disorders. Outcome was assessed at discharge from the hospital, and then followed up 6 and 12 months later. Pulmonary disorders were determined by the PaO 2 /FiO 2 ratio and radiography. The areas under the ROC curves (AUCs) were used to determine the predictive power of these factors. In the group with good short-term outcomes cTnI elevation on the second day after aSAH was significantly lower (p = .00007) than in patients with poor short-term outcomes. The same trend was observed after 6 months, although there were different results 12 months from the onset (p = .024 and n.s., respectively). A higher peak of cTnI was observed in the group with a pathological X-ray (p = .008) and pathological PaO 2 /FiO 2 ratio (p ≪ .001). cTnI was an accurate predictor of short-term outcomes (AUC = 0.741, p ≪ .001) and the outcome after 6 months (AUC = 0.688, p = .015). The results showed that cardiopulmonary abnormalities perform well as predictive factors for short- and long-term outcomes after aSAH.

High-intensity interval training has beneficial effects on cardiac remodeling through local renin-angiotensin system modulation in mice fed high-fat or high-fructose diets.

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de Oliveira Sá, Guilherme; Dos Santos Neves, Vívian; de Oliveira Fraga, Shyrlei R; Souza-Mello, Vanessa; Barbosa-da-Silva, Sandra

2017-11-15

HIIT (high-intensity interval training) has the potential to reduce cardiometabolic risk factors, but the effects on cardiac remodeling and local RAS (renin-angiotensin system) in mice fed high-fat or high-fructose diets still need to be fully addressed. Sixty male C57BL/6 mice (12weeks old) were randomly divided into three groups, control (C), High-fat (HF), or High-fructose diet (HRU) and were monitored for eight weeks before being submitted to the HIIT. Each group was randomly assigned to 2 subgroups, one subgroup was started on a 12-week HIIT protocol (T=trained group), while the other subgroup remained non-exercised (NT=not-trained group). HIIT reduced BM and systolic blood pressure in high-fat groups, while enhanced insulin sensitivity after high-fat or high-fructose intake. Moreover, HIIT reduced left ventricular hypertrophy in HF-T and HFRU-T. Notably, HIIT modulated key factors in the local left ventricular renin-angiotensin-system (RAS): reduced protein expression of renin, ACE (Angiotensin-converting enzyme), and (Angiotensin type 2 receptor) AT2R in HF-T and HFRU-T groups but reduced (Angiotensin type 1 receptor) AT1R protein expression only in the high-fat trained group. HIIT modulated ACE2/Ang (1-7)/Mas receptor axis. ACE2 mRNA gene expression was enhanced in HF-T and HFRU-T groups, complying with elevated Mas (Mas proto-oncogene, G protein-coupled receptor) receptor mRNA gene expression after HIIT. This study shows the effectiveness of HIIT sessions in producing improvements in insulin sensitivity and mitigating LV hypertrophy, though hypertension was controlled only in the high-fat-fed submitted to HIIT protocol. Local RAS system in the heart mediates these findings and receptor MAS seems to play a pivotal role when it comes to the amelioration of cardiac structural and functional remodeling due to HIIT. Copyright © 2017 Elsevier Inc. All rights reserved.

Cardioprotective Effects of Tualang Honey: Amelioration of Cholesterol and Cardiac Enzymes Levels.

Science.gov (United States)

Khalil, Md Ibrahim; Tanvir, E M; Afroz, Rizwana; Sulaiman, Siti Amrah; Gan, Siew Hua

2015-01-01

The present study was designed to investigate the cardioprotective effects of Malaysian Tualang honey against isoproterenol- (ISO-) induced myocardial infarction (MI) in rats by investigating changes in the levels of cardiac marker enzymes, cardiac troponin I (cTnI), triglycerides (TG), total cholesterol (TC), lipid peroxidation (LPO) products, and antioxidant defense system combined with histopathological examination. Male albino Wistar rats (n = 40) were pretreated orally with Tualang honey (3 g/kg/day) for 45 days. Subcutaneous injection of ISO (85 mg/kg in saline) for two consecutive days caused a significant increase in serum cardiac marker enzymes (creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and aspartate transaminase (AST)), cTnI, serum TC, and TG levels. In addition, ISO-induced myocardial injury was confirmed by a significant increase in heart lipid peroxidation (LPO) products (TBARS) and a significant decrease in antioxidant enzymes (SOD, GPx, GRx, and GST). Pretreatment of ischemic rats with Tualang honey conferred significant protective effects on all of the investigated biochemical parameters. The biochemical findings were further confirmed by histopathological examination in both Tualang-honey-pretreated and ISO-treated hearts. The present study demonstrates that Tualang honey confers cardioprotective effects on ISO-induced oxidative stress by contributing to endogenous antioxidant enzyme activity via inhibition of lipid peroxidation.

Elevated serum osteoprotegerin levels predict in-hospital major adverse cardiac events in patients with ST elevation myocardial infarction.

Science.gov (United States)

Çanga, Aytun; Durakoğlugil, Murtaza Emre; Erdoğan, Turan; Kirbaş, Aynur; Yilmaz, Adnan; Çiçek, Yüksel; Ergül, Elif; Çetin, Mustafa; Kocaman, Sinan Altan

2012-11-01

The aim of our study was to investigate whether osteoprotegerin (OPG) is related to in-hospital major adverse cardiac events (MACE) and reperfusion parameters in patients with ST elevation myocardial infarction (STEMI). The OPG/receptor activator of nuclear factor-κB (RANK)/RANK ligand pathway has recently been associated with atherosclerosis. OPG is a predictor of cardiovascular events in patients with acute coronary syndrome. This study included 96 consecutive patients with STEMI undergoing primary percutaneous coronary intervention (PCI). Two groups with equal number of patients were formed according to median OPG level. The association of OPG levels on admission with post-procedural reperfusion parameters, and in-hospital MACE were investigated. Patients with higher OPG levels displayed higher neutrophil/lymphocyte ratio, admission troponin, admission glucose, and high-sensitive C-reactive protein. Higher OPG levels were associated with increased thrombolysis in myocardial infarction (TIMI) risk score, TIMI risk index, pain to balloon time, need for inotropic support, shock, and MACE, mainly driven by death. Reperfusion parameters were not different between the two groups. TIMI risk score, TIMI risk index, myocardial blush grade, estimated glomerular filtration rate (eGFR), number of obstructed vessels, and OPG significantly predicted adverse cardiac events. Multiple logistic regression analysis revealed OPG as an independent predictor of MACE as well as eGFR, number of obstructed vessels, and corrected TIMI frame count. OPG, a bidirectional molecule displaying both atheroprotective and pro-atherosclerotic properties, is currently known as a marker of inflammation and a predictor of cardiovascular mortality. The present study, for the first time, demonstrated that an increased OPG level is related to in-hospital adverse cardiovascular events after primary PCI in patients with STEMI. Copyright © 2012 Japanese College of Cardiology. Published by Elsevier Ltd

A randomized cross-over study of the acute effects of running 5 km on glucose, insulin, metabolic rate, cortisol and Troponin T

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