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Health Technology Assessment... 2013Current practice for suspected acute coronary syndrome (ACS) involves troponin testing 10-12 hours after symptom onset to diagnose myocardial infarction (MI). Patients... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Current practice for suspected acute coronary syndrome (ACS) involves troponin testing 10-12 hours after symptom onset to diagnose myocardial infarction (MI). Patients with a negative troponin can be investigated further with computed tomographic coronary angiography (CTCA) or exercise electrocardiography (ECG).
OBJECTIVES
We aimed to estimate the diagnostic accuracy of early biomarkers for MI, the prognostic accuracy of biomarkers for major adverse cardiac adverse events (MACEs) in troponin-negative patients, the diagnostic accuracy of CTCA and exercise ECG for coronary artery disease (CAD) and the prognostic accuracy of CTCA and exercise ECG for MACEs in patients with suspected ACS. We then aimed to estimate the cost-effectiveness of using alternative biomarker strategies to diagnose MI, and using biomarkers, CTCA and exercise ECG to risk-stratify troponin-negative patients.
DATA SOURCES
We searched MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations; Cumulative Index of Nursing and Allied Health Literature (CINAHL), EMBASE, Web of Science, Cochrane Central Database of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews (CDSR), NHS Database of Abstracts of Reviews of Effects (DARE) and the Health Technology Assessment database from 1985 (CTCA review) or 1995 (biomarkers review) to November 2010, reviewed citation lists and contacted experts to identify relevant studies.
REVIEW METHODS
Diagnostic studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool and prognostic studies using a framework adapted for the project. Meta-analysis was conducted using bayesian Markov chain Monte Carlo simulation. We developed a decision-analysis model to evaluate the cost-effectiveness of alternative biomarker strategies to diagnose MI, and the cost-effectiveness of biomarkers, CTCA or exercise ECG to risk-stratify patients with a negative troponin. Strategies were applied to a theoretical cohort of patients with suspected ACS. Cost-effectiveness was estimated as the incremental cost per quality-adjusted life-year (QALY) of each strategy compared with the next most effective, taking a health-service perspective and a lifetime horizon.
RESULTS
Sensitivity and specificity (95% predictive interval) were 77% (29-96%) and 93% (46-100%) for troponin I, 80% (33-97%) and 91% (53-99%) for troponin T (99th percentile threshold), 81% (50-95%) and 80% (26-98%) for quantitative heart-type fatty acid-binding protein (H-FABP), 68% (11-97%) and 92% (20-100%) for qualitative H-FABP, 77% (19-98%) and 39% (2-95%) for ischaemia-modified albumin and 62% (35-83%) and 83% (35-98%) for myoglobin. CTCA had 94% (61-99%) sensitivity and 87% (16-100%) specificity for CAD. Positive CTCA and positive-exercise ECG had relative risks of 5.8 (0.6-24.5) and 8.0 (2.3-22.7) for MACEs. In most scenarios in the economic analysis presentation, high-sensitivity troponin measurement was the most effective strategy with an incremental cost-effectiveness ratio (ICER) of less than the £20,000-30,000/QALY threshold (ICER £7487-17,191/QALY). CTCA appeared to be the most cost-effective strategy for patients with a negative troponin, with an ICER of £11,041/QALY. However, when a lower MACE rate was assumed, CTCA had a high ICER (£262,061/QALY) and the no-testing strategy was optimal.
LIMITATIONS
There was substantial variation between the primary studies and heterogeneity in their results. Findings of the economic model were dependent on assumptions regarding the value of detecting and treating positive cases.
CONCLUSIONS
Although presentation troponin has suboptimal sensitivity, measurement of a 10-hour troponin level is unlikely to be cost-effective in most scenarios compared with a high-sensitivity presentation troponin. CTCA may be a cost-effective strategy for troponin-negative patients, but further research is required to estimate the effect of CTCA on event rates and health-care costs.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Acute Coronary Syndrome; Bayes Theorem; Biomarkers; Cost-Benefit Analysis; Decision Support Techniques; Electrocardiography; Exercise Test; Fatty Acid Binding Protein 3; Fatty Acid-Binding Proteins; Humans; Models, Econometric; Myocardial Infarction; Myoglobin; Prognosis; Quality-Adjusted Life Years; Sensitivity and Specificity; Serum Albumin; Serum Albumin, Human; Troponin T
PubMed: 23331845
DOI: 10.3310/hta17010 -
Biomedical Journal Apr 2021The association between acute infections and cardiac injury, including myocarditis and acute myocardial infarction, is now well established. We have performed a...
The association between acute infections and cardiac injury, including myocarditis and acute myocardial infarction, is now well established. We have performed a systematic literature review for analyzing the results of epidemiological studies that measured cardiac troponins (cTn) in patients with Influenza virus infections. Overall, 14 articles were finally identified and analyzed. Taken together, the results of the scientific literature suggest that cTn elevation is a relatively rare phenomenon in patients with Influenza virus infection, with frequency generally comprised between 0 and 33%, more likely in elderly patients with significant comorbidities. In patients with modest cTn elevations, this phenomenon is apparently self-limited, transient and reversible, and especially involves patients with Influenza A (especially H1N1). In the minority of patients exhibiting an abrupt appearance of cardiovascular symptoms and concomitant elevation of cTn values, the relative increase of this biomarker reflects the presence of an underlying cardiac injury, that can be either myocarditis or an acute ischemic episode. Enhanced cTn values can also be more frequently observed in Influenza patients with complicated disease, in those developing acute respiratory distress syndrome and cardiac dysfunction, as well as in those at higher risk of death. cTn measurement shall be considered a valuable option in all patients developing acute cardiovascular symptoms during Influenza virus infections, as well as in those bearing cardiac or extra-cardiac comorbidities who bear a higher risk of complications.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Female; Humans; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H7N9 Subtype; Influenza, Human; Male; Middle Aged; Myocardial Infarction; Troponin; Young Adult
PubMed: 33097442
DOI: 10.1016/j.bj.2020.06.001 -
European Journal of Sport Science May 2021Genetic variation is responsible for a large amount of the inter-individual performance disparities seen in sport. As such, in the last ten years genetic association...
Genetic variation is responsible for a large amount of the inter-individual performance disparities seen in sport. As such, in the last ten years genetic association studies have become more common; with one of the most frequently researched sports being football. However, the progress and methodological rigour of genetic association research in football is yet to be evaluated. Therefore, the aim of this paper was to identify and evaluate all genetic association studies involving football players and outline where and how future research should be directed. Firstly, a systematic search was conducted in the Pubmed and SPORTDiscus databases, which identified 80 eligible studies. Progression analysis revealed that 103 distinct genes have been investigated across multiple disciplines; however, research has predominately focused on the association of the or gene. Furthermore, 55% of the total studies have been published within the last four years; showcasing that genetic association research in football is increasing at a substantial rate. However, there are several methodological inconsistencies which hinder research implications, such as; inadequate description or omission of ethnicity and on-field positions. Furthermore, there is a limited amount of research on several key areas crucial to footballing performance, in particular; psychological related traits. Moving forward, improved research designs, larger sample sizes, and the utilisation of genome-wide and polygenic profiling approaches are recommended. Finally, we introduce the Football Gene Project, which aims to address several of these limitations and ultimately facilitate greater individualised athlete development within football.
Topics: Actinin; Adolescent; Adult; Athletic Performance; Cell Cycle Proteins; Child; Epigenesis, Genetic; Female; Genetic Association Studies; Genetic Variation; Genome-Wide Association Study; Humans; Male; Oncogene Proteins; Peptidyl-Dipeptidase A; Soccer; Sports; Young Adult
PubMed: 32466725
DOI: 10.1080/17461391.2020.1776401 -
International Journal of Molecular... Mar 2020Cardiac complications after a stroke are the second leading cause of death worldwide, affecting the treatment and outcomes of stroke patients. Cardiac biomarkers such as... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cardiac complications after a stroke are the second leading cause of death worldwide, affecting the treatment and outcomes of stroke patients. Cardiac biomarkers such as cardiac troponin (cTn), brain natriuretic peptide (BNP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) have been frequently reported in patients undergoing a stroke. The aim of the present study is to meta-analyze the relationship between changes in such cardiac biomarkers and stroke and to present a systematic review of the previous literature, so as to explore the brain-heart axis.
METHODS
We searched four online databases pertinent to the literature, including PubMed, Embase, the Cochrane Library, and the Web of Science. Then, we performed a meta-analysis to investigate changes in cTn, BNP, and NT-proBNP associated with different types of stroke.
RESULTS AND CONCLUSIONS
A significant increase in cTnI concentration was found in patients exhibiting a brain hemorrhage. BNP increased in cases of brain infarction, while the NT-proBNP concentration was significantly elevated in patients suffering an acute ischemic stroke and brain hemorrhage, indicating cardiac damage and dysfunction after a stroke. Our analysis suggests that several potential mechanisms may be involved in the brain-heart axis. Finally, clinicians should pay careful attention to monitoring cardiac function in the treatment of cerebrovascular diseases in order to provide a timely and more accurate treatment.
Topics: Biomarkers; Heart Diseases; Humans; Intracranial Hemorrhages; Natriuretic Peptide, Brain; Peptide Fragments; Stroke; Troponin I
PubMed: 32231119
DOI: 10.3390/ijms21072347 -
PloS One 2019Increased postoperative cardiac troponin (cTn) independently predicts short-term mortality. Previous studies suggest that preoperative cTn also predicts major adverse... (Meta-Analysis)
Meta-Analysis
Prognostic performance of preoperative cardiac troponin and perioperative changes in cardiac troponin for the prediction of major adverse cardiac events and mortality in noncardiac surgery: A systematic review and meta-analysis.
BACKGROUND
Increased postoperative cardiac troponin (cTn) independently predicts short-term mortality. Previous studies suggest that preoperative cTn also predicts major adverse cardiovascular events (MACE) and mortality after noncardiac surgery. The value of preoperative and perioperative changes in cTn as a prognostic tool for adverse outcomes has been sparsely investigated.
METHODS AND FINDINGS
A systematic review and meta-analysis of the prognostic value of cTns for adverse outcome was conducted. Adverse outcome was defined as short-term (in-hospital or <30 days) and long-term (>30 days) MACE and/or all-cause mortality, in adult patients undergoing noncardiac surgery. The study protocol (CRD42018094773) was registered with an international prospective register of systematic reviews (PROSPERO). Preoperative cTn was a predictor of short- (OR 4.3, 95% CI 2.9-6.5, p<0.001, adjusted OR 5.87, 95% CI 3.24-10.65, p<0.001) and long-term adverse outcome (OR 4.2, 95% CI 1.0-17.3, p = 0.05, adjusted HR 2.0, 95% CI 1.4-3.0, p<0.001). Perioperative change in cTn was a predictor of short-term adverse outcome (OR 10.1, 95% CI 3.2-32.3, p<0.001). It was not possible to conduct pooled analyses for adjusted estimates of perioperative change in cTn as predictor of short- (a single study identified) and long-term (no studies identified) adverse outcome. Further, it was not possible to conduct pooled analyses for unadjusted estimates of perioperative change in cTn as predictor of long-term adverse outcome, since only one study was identified. Bivariate analysis of sensitivities and specificities were performed, and overall prognostic performance was summarized using summary receiver operating characteristic (SROC) curves. The pooled sensitivity and specificity for preoperative cTn and short-term adverse outcome was 0.43 and 0.86 respectively (area under the SROC curve of 0.68). There were insufficient studies to construct SROCs for perioperative changes in cTn and for long-term adverse outcome.
CONCLUSION
Our study indicates that although preoperative cTn and perioperative change in cTn might be valuable predictors of MACE and/or all-cause mortality in adult noncardiac surgical patients, its overall prognostic performance remains uncertain. Future large, representative, high-quality studies are needed to establish the potential role of cTns in perioperative cardiac risk stratification.
Topics: Biomarkers; Humans; Musculoskeletal Diseases; Nervous System Diseases; Perioperative Care; Preoperative Care; Prognosis; Risk Assessment; Survival Rate; Troponin I; Urologic Diseases
PubMed: 31009468
DOI: 10.1371/journal.pone.0215094 -
Cardiology 2015Coronary artery bypass grafting (CABG) is a key and effective surgical treatment modality for coronary artery disease. Unfortunately, ischemia-reperfusion injury during... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Coronary artery bypass grafting (CABG) is a key and effective surgical treatment modality for coronary artery disease. Unfortunately, ischemia-reperfusion injury during and after CABG can lead to reversible and irreversible myocardial damage. Trimetazidine [1-(2,3,4-trimethoxybenzyl)piperazine dihydrochloride] is a metabolic anti-ischemic agent with demonstrated cardioprotective effects; however, its effects with respect to myocardial preservation in CABG patients remain unclear.
METHODS
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to investigate the effectiveness of myocardial preservation of preoperative trimetazidine therapy in CABG patients by assessing the postoperative levels of several blood-based biochemical markers of myocardial injury, including creatine kinase (CK), creatine kinase-muscle and brain (CK-MB), creatine phosphokinase (CPK), troponin T (TnT) and troponin I (TnI). The RCTs were classified into two subgroup analyses by the timing of sample collection (either ≤12 or >12 h after CABG).
RESULTS
Six RCTs were finally included in the meta-analysis. The pooled effect sizes showed significantly lower postoperative levels of CK, CK-MB, TnT and TnI in the trimetazidine-treated CABG patients relative to control CABG patients. However, there were no significant differences in the postoperative CPK levels between trimetazidine-treated CABG patients relative to control CABG patients. In both the ≤12 and >12 h post-CABG subgroup analyses, significant differences in CK, CK-MB, TnT and TnI were detected between the trimetazidine-treated CABG patients relative to control CABG patients.
CONCLUSIONS
Preoperative trimetazidine therapy appears to have a positive effect on myocardial preservation in CABG patients.
Topics: Biomarkers; Cardiotonic Agents; Coronary Artery Bypass; Creatine Kinase, MB Form; Humans; Myocardial Reperfusion Injury; Postoperative Complications; Preoperative Care; Randomized Controlled Trials as Topic; Trimetazidine; Troponin; Vasodilator Agents
PubMed: 25871315
DOI: 10.1159/000375289 -
Journal of Cardiology Sep 2021Elevation of high-sensitivity troponin-T (hs-TnT) is linked to cardiovascular morbidity and mortality. However, its prognostic value for survival and cardiovascular... (Review)
Review
BACKGROUND
Elevation of high-sensitivity troponin-T (hs-TnT) is linked to cardiovascular morbidity and mortality. However, its prognostic value for survival and cardiovascular events and its relation to clinical characteristics and cardiac function parameters in clinically asymptomatic adults with congenital heart disease (ACHD) needs further exploration.
METHODS
A systematic literature search was performed in PubMed and Cochrane from 2010 to May 2020 for hs-TnT as a prognostic marker in ACHD. Three independent reviewers evaluated the articles according to the Study Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies of the National Heart, Lung, and Blood Institute. Overall, eight studies with a total of 2162 ACHD patients (18-63 years) were included.
RESULTS
Hs-TnT level was elevated in 8-26% of asymptomatic ACHD. The follow-up for all-cause mortality and cardiovascular events ranged from 3.0 to 5.6 years and in 8-38% of the participants cardiac endpoints were reached. Throughout the included studies, elevated hs-TnT was found to be an independent predictor for survival and heart failure in stable ACHD. Serial hs-TnT measurement was found to be beneficial over single measurement. Hs-TnT levels were correlated with male sex, higher age, and higher New York Heart Association class and associated with several cardiac dysfunction parameters.
CONCLUSION
More scientific research investigating the prognostic value of hs-TnT in stable ACHD is needed and the clinical relevance to guide aftercare has still to be determined.
Topics: Adult; Biomarkers; Cross-Sectional Studies; Heart Defects, Congenital; Humans; Male; Prognosis; Troponin T
PubMed: 33678488
DOI: 10.1016/j.jjcc.2021.02.008 -
Journal of the American Heart... Mar 2019Background The recent introduction of high-sensitivity cardiac troponin (hs-cTn) assays has allowed clinicians to measure hs-cTn before and after cardiac stress testing,... (Meta-Analysis)
Meta-Analysis
Background The recent introduction of high-sensitivity cardiac troponin (hs-cTn) assays has allowed clinicians to measure hs-cTn before and after cardiac stress testing, but the hs-cTn release pattern and potential utility in identifying inducible myocardial ischemia are unclear. We thus conducted a systematic review and meta-analysis to improve our understanding of hs-cTn release associated with exercise and pharmacological stress testing. Methods and Results Studies published between January 2008 and July 2016 that reported hs-cTn change values (high-sensitivity cardiac troponin T [hs-cTnT] or high-sensitivity cardiac troponin I [hs-cTnI]) in relation to cardiac stress testing were searched and reviewed by 2 independent screeners. Primary outcomes were pooled estimates of absolute and relative hs-cTn changes after cardiac stress test, stratified by the presence of inducible myocardial ischemia. This meta-analysis included 11 studies (n=2432 patients). After exercise stress testing, hs-cTnT increased by 0.5 ng/L or 11% (6 studies, n=406) and hs-cTnI by 2.4 ng/L or 41% (4 studies, n=365) in patients with inducible myocardial ischemia versus hs-cTnT by 1.1 ng/L or 18% (8 studies, n=629; P=0.29) and hs-cTnI by 1.8 ng/L or 72% (4 studies, n=831; P=0.61) in patients who did not develop inducible myocardial ischemia. After pharmacological stress test, hs-cTnT changed by -0.1 ng/L or -0.4% (6 studies, n=251) and hs-cTnI by 2.4 ng/L or 32% (2 studies, n=108) in patients with inducible myocardial ischemia versus hs-cTnT by 0.7 ng/L or 11% (5 studies, n=443, P=0.44) and hs-cTnI by 1.7 ng/L or 38% (2 studies, n=116; P=0.62) in patients who did not develop inducible myocardial ischemia. Conclusions hs-cTn rising patterns after exercise and pharmacological stress testing appear inconsistent and comparably small, and do not appear to be correlated with inducible myocardial ischemia.
Topics: Biomarkers; Electrocardiography; Exercise Test; Humans; Myocardial Ischemia; Reproducibility of Results; Troponin
PubMed: 30871395
DOI: 10.1161/JAHA.118.008626 -
Medical Sciences (Basel, Switzerland) May 2021The optimal timing of aortic valve replacement (AVR) remains controversial. Several biomarkers reflect the underlying pathophysiological processes in aortic stenosis... (Meta-Analysis)
Meta-Analysis
The optimal timing of aortic valve replacement (AVR) remains controversial. Several biomarkers reflect the underlying pathophysiological processes in aortic stenosis (AS) and may be of use as mortality predictors. The aim of this systematic review and meta-analysis is to evaluate the blood biomarkers utilised in AS and assess whether they associate with mortality. PubMed and Embase were searched for studies reporting baseline biomarker level and mortality outcomes in patients with AS. A total of 83 studies met the inclusion criteria and were systematically reviewed. Of these, 21 reporting brain natriuretic peptide (BNP), N-terminal pro B-type natriuretic peptide (NT-proBNP), Troponin and Galectin-3 were meta-analysed. Pooled analysis demonstrated that all-cause mortality was significantly associated with elevated baseline levels of BNP (HR 2.59; 95% CI 1.95-3.44; < 0.00001), NT-proBNP (HR 1.73; 95% CI 1.45-2.06; = 0.00001), Troponin (HR 1.65; 95% CI 1.31-2.07; < 0.0001) and Galectin-3 (HR 1.82; 95% CI 1.27-2.61; < 0.001) compared to lower baseline biomarker levels. Elevated levels of baseline BNP, NT-proBNP, Troponin and Galectin-3 were associated with increased all-cause mortality in a population of patients with AS. Therefore, a change in biomarker level could be considered to refine optimal timing of intervention. The results of this meta-analysis highlight the importance of biomarkers in risk stratification of AS, regardless of symptom status.
Topics: Aortic Valve; Aortic Valve Stenosis; Biomarkers; Galectin 3; Humans; Natriuretic Peptide, Brain; Troponin
PubMed: 34067808
DOI: 10.3390/medsci9020029 -
Respiratory Medicine Oct 2019To evaluate whether elevated levels of cardiac troponin increases the risk of mortality in patients with acute PE. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To evaluate whether elevated levels of cardiac troponin increases the risk of mortality in patients with acute PE.
METHODS
We conducted a systematic review and meta-analysis with rigorous statistical evaluation using publications (2000-2018) from Cochrane Library, MEDLINE, PubMed, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), WHO International Clinical Trials Registry Platform, and Google Scholar databases. We searched for retrospective, prospective, and randomized controlled trials (RCT) or quasi-RCT studies that assessed the effect of elevated troponin versus normal levels on the outcomes of PE. The main outcome of interest was all-cause mortality. Extracted data included authors, the origin of studies, source population, study settings and duration, inclusion/exclusion criteria, data sources and measurement, sample size, and mortality. Data heterogeneity was assessed using the Cochrane Q homogeneity test with a significance set at p < 0.10. If the studies were statistically homogeneous, a fixed effect model was selected.
RESULTS
Out of 1825 references, 46 analytical studies were included with a total of 10842 patients with PE. The effect of elevated troponin on mortality had a pooled odd ratio (OR) of 4.33 for all studies, 3.7for HsTnT, 14.81 for HsTnI, 7.85 for cTnT, 2.81 for cTnI, 9.02 for low-risk PE and 4.80 for 90-day mortality. The pooled negative likelihood ratios for all-cause mortality using HsTnI, cTnI and cTnT assay were 0.21, 0.33 and 0.65, respectively.
CONCLUSION
Regardless of the troponin assay, pooled analysis indicates that elevated troponin is significantly associated with higher mortality in patients with PE.
Topics: Acute Disease; Female; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Predictive Value of Tests; Prognosis; Prospective Studies; Pulmonary Embolism; Randomized Controlled Trials as Topic; Retrospective Studies; Risk; Sensitivity and Specificity; Troponin; Troponin I; Troponin T
PubMed: 31476570
DOI: 10.1016/j.rmed.2019.08.011