Publications by authors named "Alma Mingels"

39 Publications

Meta-Analysis Evaluating High-Sensitivity Cardiac Troponin T Kinetics after Coronary Artery Bypass Grafting in Relation to the Current Definitions of Myocardial Infarction.

Am J Cardiol 2021 Nov 8. Epub 2021 Nov 8.

Department of Central Diagnostic Laboratory; Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands.

Various definitions of myocardial infarction type 5 after coronary artery bypass grafting (CABG) have been proposed (myocardial infarction [MI-5], also known as peri-procedural MI), using different biomarkers and different and arbitrary cut-off values. This meta-analysis aims to determine the expected release of high-sensitivity cardiac troponin T (hs-cTnT) after CABG in general and after uncomplicated surgery and off-pump CABG in particular. A systematic search was applied to 3 databases. Studies on CABG as a single intervention and reporting on postoperative hs-cTnT concentrations on at least 2 different time points were included. All data on hs-cTnT concentrations were extracted, and mean concentrations at various points in time were stratified. Eventually, 15 studies were included, encompassing 2,646 patients. Preoperative hs-cTnT was 17 ng/L (95% confidence interval [CI] 13 to 20 ng/L). Hs-cTnT peaked at 6 to 8 hours postoperatively (628 ng/L, 95% CI 400 to 856 ng/L; 45x upper reference limit [URL]) and was still increased after 48 hours. In addition, peak hs-cTnT concentration was 614 ng/L (95% CI 282 to 947 ng/L) in patients with a definite uncomplicated postoperative course (i.e., without MI). For patients after off-pump CABG compared to on-pump CABG, the mean peak hs-cTnT concentration was 186 ng/L (95% CI 172 to 200 ng/L, 13 × URL) versus 629 ng/L (95% CI 529 to 726 ng/L, 45 × URL), respectively. In conclusion, postoperative hs-cTnT concentrations surpass most of the currently defined cut-off values for MI-5, even in perceived uncomplicated surgery, suggesting thorough reassessment. Hs-cTnT release differences following on-pump CABG versus off-pump CABG were observed, implying the need for different cut-off values for different surgical strategies.
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http://dx.doi.org/10.1016/j.amjcard.2021.09.049DOI Listing
November 2021

Towards an improved definition of periprocedural myocardial infarction: The role of high-sensitivity cardiac troponins.

J Card Surg 2022 Jan 24;37(1):162-164. Epub 2021 Oct 24.

Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherland.

In the past few years, many have disputed the optimal biomarker for confirming or ruling out a diagnosis of periprocedural myocardial infarction (PMI) and the optimal cut-off concentrations to apply. In this issue of the Journal of Cardiac Surgery, Niclauss et al. performed a retrospective analysis of CK-MB and high-sensitivity cardiac troponin T (hs-cTnT) dynamics and peak concentrations following different cardiac surgical interventions in 400 patients during a 2-year period in a single center. The authors found that CK-MB and hs-cTnT predict PMI with a comparable diagnostic accuracy and discriminatory power >95%. They also attempted to propose an improved, more sensitive threshold of hs-cTnT for PMI. Their findings could have implications for clinical practice, but more research is warranted to identify more appropriate cut-offs. This could include hs-cTnT release pattern, slope steepness, and changes. Ultimately, this could results in patient-specific model, able to predict expected and abnormal ranges of hs-cTnT release, enabling an improved and timely diagnosis of PMI.
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http://dx.doi.org/10.1111/jocs.16107DOI Listing
January 2022

Cardiac Troponin T: The Impact of Posttranslational Modifications on Analytical Immunoreactivity in Blood up to the Excretion in Urine.

Adv Exp Med Biol 2021 ;1306:41-59

Unit of Clinical Chemistry, Central Diagnostic Laboratory, Maastricht University Medical Center, Maastricht, The Netherlands.

Cardiac troponin T (cTnT) is a sensitive and specific biomarker for detecting cardiac muscle injury. Its concentration in blood can be significantly elevated outside the normal reference range under several pathophysiological conditions. The classical analytical method in routine clinical analysis to detect cTnT in serum or plasma is a single commercial immunoassay, which is designed to quantify the intact cTnT molecule. The targeted epitopes are located in the central region of the cTnT molecule. However, in blood cTnT exists in different biomolecular complexes and proteoforms: bound (to cardiac troponin subunits or to immunoglobulins) or unbound (as intact protein or as proteolytic proteoforms). While proteolysis is a principal posttranslational modification (PTM), other confirmed PTMs of the proteoforms include N-terminal initiator methionine removal, N-acetylation, O-phosphorylation, O-(N-acetyl)-glucosaminylation, N(ɛ)-(carboxymethyl)lysine modification and citrullination. The immunoassay probably detects several of those cTnT biomolecular complexes and proteoforms, as long as they have the centrally targeted epitopes in common. While analytical cTnT immunoreactivity has been studied predominantly in blood, it can also be detected in urine, although it is unclear in which proteoform cTnT immunoreactivity is present in urine. This review presents an overview of the current knowledge on the pathophysiological lifecycle of cTnT. It provides insight into the impact of PTMs, not only on the analytical immunoreactivity, but also on the excretion of cTnT in urine as one of the waste routes in that lifecycle. Accordingly, and after isolating the proteoforms from urine of patients suffering from proteinuria and acute myocardial infarction, the structures of some possible cTnT proteoforms are reconstructed using mass spectrometry and presented.
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http://dx.doi.org/10.1007/978-3-030-63908-2_4DOI Listing
May 2021

Cardiovascular magnetic resonance accurately detects obstructive coronary artery disease in suspected non-ST elevation myocardial infarction: a sub-analysis of the CARMENTA Trial.

J Cardiovasc Magn Reson 2021 03 22;23(1):40. Epub 2021 Mar 22.

Department of Cardiology, Maastricht UMC+, Maastricht, The Netherlands.

Background: Invasive coronary angiography (ICA) is still the reference test in suspected non-ST elevation myocardial infarction (NSTEMI), although a substantial number of patients do not have obstructive coronary artery disease (CAD). Early cardiovascular magnetic resonance (CMR) may be a useful gatekeeper for ICA in this setting. The main objective was to investigate the accuracy of CMR to detect obstructive CAD in NSTEMI.

Methods: This study is a sub-analysis of a randomized controlled trial investigating whether a non-invasive imaging-first strategy safely reduced the number of ICA compared to routine clinical care in suspected NSTEMI (acute chest pain, non-diagnostic electrocardiogram, high sensitivity troponin T > 14 ng/L), and included 51 patients who underwent CMR prior to ICA. A stepwise approach was used to assess the diagnostic accuracy of CMR to detect (1) obstructive CAD (diameter stenosis ≥ 70% by ICA) and (2) an adjudicated final diagnosis of acute coronary syndrome (ACS). First, in all patients the combination of cine, T2-weighted and late gadolinium enhancement (LGE) imaging was evaluated for the presence of abnormalities consistent with a coronary etiology in any sequence. Hereafter and only when the scan was normal or equivocal, adenosine stress-perfusion CMR was added.

Results: Of 51 patients included (63 ± 10 years, 51% male), 34 (67%) had obstructive CAD by ICA. The sensitivity, specificity and overall accuracy of the first step to diagnose obstructive CAD were 79%, 71% and 77%, respectively. Additional vasodilator stress-perfusion CMR was performed in 19 patients and combined with step one resulted in an overall sensitivity of 97%, specificity of 65% and accuracy of 86%. Of the remaining 17 patients with non-obstructive CAD, 4 (24%) had evidence for a myocardial infarction on LGE, explaining the modest specificity. The sensitivity, specificity and overall accuracy to diagnose ACS (n = 43) were 88%, 88% and 88%, respectively.

Conclusion: CMR accurately detects obstructive CAD and ACS in suspected NSTEMI. Non-obstructive CAD is common with CMR still identifying an infarction in almost one-quarter of patients. CMR should be considered as an early diagnostic approach in suspected NSTEMI.

Trial Registration: The CARMENTA trial has been registered at ClinicalTrials.gov with identifier NCT01559467.
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http://dx.doi.org/10.1186/s12968-021-00723-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983380PMC
March 2021

Mass Spectrometry Spatial-Omics on a Single Conductive Slide.

Anal Chem 2021 02 7;93(4):2527-2533. Epub 2021 Jan 7.

Maastricht MultiModal Molecular Imaging (M4I) Institute, Division of Imaging Mass Spectrometry, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands.

Mass spectrometry imaging (MSI) can analyze the spatial distribution of hundreds of different molecules directly from tissue sections usually placed on conductive glass slides to provide conductivity on the sample surface. Additional experiments are often required for molecular identification using consecutive sections on membrane slides compatible with laser capture microdissection (LMD). In this work, we demonstrate for the first time the use of a single conductive slide for both matrix-assisted laser desorption ionization (MALDI)-MSI and direct proteomics. In this workflow, regions of interest can be directly ablated with LMD while preserving protein integrity. These results offer an alternative for MSI-based multimodal spatial-omics.
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http://dx.doi.org/10.1021/acs.analchem.0c04572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859928PMC
February 2021

Serial measurements in COVID-19-induced acute respiratory disease to unravel heterogeneity of the disease course: design of the Maastricht Intensive Care COVID cohort (MaastrICCht).

BMJ Open 2020 09 29;10(9):e040175. Epub 2020 Sep 29.

Department of Intensive Care, Maastricht University Medical Center+, Maastricht, The Netherlands.

Introduction: The course of the disease in SARS-CoV-2 infection in mechanically ventilated patients is unknown. To unravel the clinical heterogeneity of the SARS-CoV-2 infection in these patients, we designed the prospective observational Maastricht Intensive Care COVID cohort (MaastrICCht). We incorporated serial measurements that harbour aetiological, diagnostic and predictive information. The study aims to investigate the heterogeneity of the natural course of critically ill patients with a SARS-CoV-2 infection.

Methods And Analysis: Mechanically ventilated patients admitted to the intensive care with a SARS-CoV-2 infection will be included. We will collect clinical variables, vital parameters, laboratory variables, mechanical ventilator settings, chest electrical impedance tomography, ECGs, echocardiography as well as other imaging modalities to assess heterogeneity of the course of a SARS-CoV-2 infection in critically ill patients. The MaastrICCht is also designed to foster various other studies and registries and intends to create an open-source database for investigators. Therefore, a major part of the data collection is aligned with an existing national intensive care data registry and two international COVID-19 data collection initiatives. Additionally, we create a flexible design, so that additional measures can be added during the ongoing study based on new knowledge obtained from the rapidly growing body of evidence. The spread of the COVID-19 pandemic requires the swift implementation of observational research to unravel heterogeneity of the natural course of the disease of SARS-CoV-2 infection in mechanically ventilated patients. Our study design is expected to enhance aetiological, diagnostic and prognostic understanding of the disease. This paper describes the design of the MaastrICCht.

Ethics And Dissemination: Ethical approval has been obtained from the medical ethics committee (Medisch Ethische Toetsingscommissie 2020-1565/3 00 523) of the Maastricht University Medical Centre+ (Maastricht UMC+), which will be performed based on the Declaration of Helsinki. During the pandemic, the board of directors of Maastricht UMC+ adopted a policy to inform patients and ask their consent to use the collected data and to store serum samples for COVID-19 research purposes. All study documentation will be stored securely for fifteen years after recruitment of the last patient. The results will be published in peer-reviewed academic journals, with a preference for open access journals, while particularly considering deposition of the manuscripts on a preprint server early.

Trial Registration Number: The Netherlands Trial Register (NL8613).
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http://dx.doi.org/10.1136/bmjopen-2020-040175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526030PMC
September 2020

Short-term discontinuation of vagal nerve stimulation alters F-FDG blood pool activity: an exploratory interventional study in epilepsy patients.

EJNMMI Res 2019 Nov 27;9(1):101. Epub 2019 Nov 27.

Department of Radiology and Nuclear Medicine, Maastricht University Medical Center (MUMC+), P. Debyelaan 25, 6229 HX, Maastricht, The Netherlands.

Background: Vagus nerve activation impacts inflammation. Therefore, we hypothesized that vagal nerve stimulation (VNS) influenced arterial wall inflammation as measured by F-FDG uptake.

Results: Ten patients with left-sided VNS for refractory epilepsy were studied during stimulation (VNS-on) and in the hours after stimulation was switched off (VNS-off). In nine patients, F-FDG uptake was measured in the right carotid artery, aorta, bone marrow, spleen, and adipose tissue. Target-to-background ratios (TBRs) were calculated to normalize the respective standardized uptake values (SUVs) for venous blood pool activity. Median values are shown with interquartile range and compared using the Wilcoxon signed-rank test. Arterial SUVs tended to be higher during VNS-off than VNS-on [SUV all vessels 1.8 (1.5-2.2) vs. 1.7 (1.2-2.0), p = 0.051]. However, a larger difference was found for the venous blood pool at this time point, reaching statistical significance in the vena cava superior [SUV 1.3 (1.1-1.4) vs. 1.0 (0.8-1.1); p = 0.011], resulting in non-significant lower arterial TBRs during VNS-off than VNS-on. Differences in the remaining tissues were not significant. Insulin levels increased after VNS was switched off [55.0 pmol/L (45.9-96.8) vs. 48.1 pmol/L (36.9-61.8); p = 0.047]. The concurrent increase in glucose levels was not statistically significant [4.8 mmol/L (4.7-5.3) vs. 4.6 mmol/L (4.5-5.2); p = 0.075].

Conclusions: Short-term discontinuation of VNS did not show a consistent change in arterial wall F-FDG-uptake. However, VNS did alter insulin and F-FDG blood levels, possibly as a result of sympathetic activation.
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http://dx.doi.org/10.1186/s13550-019-0567-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879675PMC
November 2019

Initial Imaging-Guided Strategy Versus Routine Care in Patients With Non-ST-Segment Elevation Myocardial Infarction.

J Am Coll Cardiol 2019 11;74(20):2466-2477

Department of Cardiology, Maastricht University Medical Center, Maastricht, the Netherlands; Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands; Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, the Netherlands. Electronic address:

Background: Patients with non-ST-segment elevation myocardial infarction and elevated high-sensitivity cardiac troponin levels often routinely undergo invasive coronary angiography (ICA), but many do not have obstructive coronary artery disease.

Objectives: This study investigated whether cardiovascular magnetic resonance imaging (CMR) or computed tomographic angiography (CTA) may serve as a safe gatekeeper for ICA.

Methods: This randomized controlled trial (NCT01559467) in 207 patients (age 64 years; 62% male patients) with acute chest pain, elevated high-sensitivity cardiac troponin T levels (>14 ng/l), and inconclusive electrocardiogram compared a CMR- or CTA-first strategy with a control strategy of routine clinical care. Follow-up ICA was recommended when initial CMR or CTA suggested myocardial ischemia, infarction, or obstructive coronary artery disease (≥70% stenosis). Primary efficacy and secondary safety endpoints were referral to ICA during hospitalization and 1-year outcomes (major adverse cardiac events and complications), respectively.

Results: The CMR- and CTA-first strategies reduced ICA compared with routine clinical care (87% [p = 0.001], 66% [p < 0.001], and 100%, respectively), with similar outcome (hazard ratio: CMR vs. routine, 0.78 [95% confidence interval: 0.37 to 1.61]; CTA vs. routine, 0.66 [95% confidence interval: 0.31 to 1.42]; and CMR vs. CTA, 1.19 [95% confidence interval: 0.53 to 2.66]). Obstructive coronary artery disease after ICA was found in 61% of patients in the routine clinical care arm, in 69% in the CMR-first arm (p = 0.308 vs. routine), and in 85% in the CTA-first arm (p = 0.006 vs. routine). In the non-CMR and non-CTA arms, follow-up CMR and CTA were performed in 67% and 13% of patients and led to a new diagnosis in 33% and 3%, respectively (p < 0.001).

Conclusions: A novel strategy of implementing CMR or CTA first in the diagnostic process in non-ST-segment elevation myocardial infarction is a safe gatekeeper for ICA.
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http://dx.doi.org/10.1016/j.jacc.2019.09.027DOI Listing
November 2019

Cardiac Troponin T: Only Small Molecules in Recreational Runners After Marathon Completion.

J Appl Lab Med 2019 03 6;3(5):909-911. Epub 2018 Sep 6.

Central Diagnostic Laboratory Maastricht University Medical Center Maastricht, the Netherlands

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http://dx.doi.org/10.1373/jalm.2018.027144DOI Listing
March 2019

High-sensitivity cardiac troponin testing during and after ACS: Complexed or not?

Clin Biochem 2019 Nov 27;73:32-34. Epub 2019 Jul 27.

Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.clinbiochem.2019.07.012DOI Listing
November 2019

Multi-Site Coronary Vein Sampling Study on Cardiac Troponin T Degradation in Non-ST-Segment-Elevation Myocardial Infarction: Toward a More Specific Cardiac Troponin T Assay.

J Am Heart Assoc 2019 07 4;8(14):e012602. Epub 2019 Jul 4.

2 Central Diagnostic Laboratory Maastricht University Medical Center Maastricht The Netherlands.

Background Cardiac troponin T ( cTnT ) is seen in many other conditions besides myocardial infarction, and recent studies demonstrated distinct forms of cTnT . At present, the in vivo formation of these different cTnT forms is incompletely understood. We therefore performed a study on the composition of cTnT during the course of myocardial infarction, including coronary venous system sampling, close to its site of release. Methods and Results Baseline samples were obtained from multiple coronary venous system locations, and a peripheral artery and vein in 71 non- ST -segment-elevation myocardial infarction patients. Additionally, peripheral blood was drawn at 6- and 12-hours postcatheterization. cTnT concentrations were measured using the high-sensitivity- cTnT immunoassay. The cTnT composition was determined via gel filtration chromatography and Western blotting in an early and late presenting patient. High-sensitivity - cTnT concentrations were 28% higher in the coronary venous system than peripherally (n=71, P<0.001). Coronary venous system samples demonstrated cT n T-I-C complex, free intact cTnT , and 29 kD a and 15 to 18 kD a cTnT fragments, all in higher concentrations than in simultaneously obtained peripheral samples. While cT n T-I-C complex proportionally decreased, and disappeared over time, 15 to 18 kD a cTnT fragments increased. Moreover, cT n T-I-C complex was more prominent in the early than in the late presenting patient. Conclusions This explorative study in non- ST -segment-elevation myocardial infarction shows that cTnT is released from cardiomyocytes as a combination of cT n T-I-C complex, free intact cTnT , and multiple cTnT fragments indicating intracellular cTnT degradation. Over time, the cT n T-I-C complex disappeared because of in vivo degradation. These insights might serve as a stepping stone toward a high-sensitivity- cTnT immunoassay more specific for myocardial infarction.
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http://dx.doi.org/10.1161/JAHA.119.012602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6662151PMC
July 2019

Trends in mass spectrometry imaging for cardiovascular diseases.

Anal Bioanal Chem 2019 Jul 12;411(17):3709-3720. Epub 2019 Apr 12.

Maastricht MultiModal Molecular Imaging (M4I) Institute, Division of Imaging Mass Spectrometry, Maastricht University, Universiteitssingel 50, 6229 ER, Maastricht, The Netherlands.

Mass spectrometry imaging (MSI) is a widely established technology; however, in the cardiovascular research field, its use is still emerging. The technique has the advantage of analyzing multiple molecules without prior knowledge while maintaining the relation with tissue morphology. Particularly, MALDI-based approaches have been applied to obtain in-depth knowledge of cardiac (dys)function. Here, we discuss the different aspects of the MSI protocols, from sample handling to instrumentation used in cardiovascular research, and critically evaluate these methods. The trend towards structural lipid analysis, identification, and "top-down" protein MSI shows the potential for implementation in (pre)clinical research and complementing the diagnostic tests. Moreover, new insights into disease progression are expected and thereby contribute to the understanding of underlying mechanisms related to cardiovascular diseases.
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http://dx.doi.org/10.1007/s00216-019-01780-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594994PMC
July 2019

TSH suppression aggravates arterial inflammation - an F-FDG PET study in thyroid carcinoma patients.

Eur J Nucl Med Mol Imaging 2019 Jul 11;46(7):1428-1438. Epub 2019 Mar 11.

Department of Radiology and Nuclear Medicine, Maastricht University Medical Centre (MUMC+), P. Debyelaan 25, 6229 HX, Maastricht, The Netherlands.

Purpose: We aimed to investigate the influence of both hypothyroidism and thyroid-stimulating hormone (TSH) suppression on vascular inflammation, as assessed with F-fluorodeoxyglucose (F-FDG) positron emission tomography (PET)/computed tomography (CT).

Methods: Ten thyroid carcinoma patients underwent an F-FDG PET/CT during post-thyroidectomy hypothyroidism and during thyrotropin (TSH) suppression after I (radioiodine) ablation therapy. We analysed the F-FDG uptake in the carotids, aortic arch, ascending, descending, and abdominal aorta to investigate the effects of thyroid hormone status on arterial inflammation. Target-to-background ratios (TBRs) corrected for blood pool activity were established for all arterial territories. Results were further compared to euthyroid historic control subjects.

Results: In general, there was a trend towards higher vascular TBRs during TSH suppression than during hypothyroidism (TBR all vessels = 1.6 and 1.8, respectively, p = 0.058), suggesting a higher degree of arterial inflammation. In concurrence with this, we found increased C-reactive protein (CRP) levels after levothyroxine treatment (CRP = 2.9 mg/l and 4.8 mg/l, p = 0.005). An exploratory comparison with euthyroid controls showed significant higher TBRs during TSH suppression for the carotids, aortic arch, thoracic descending aorta, and when all vascular territories were combined (TBRp = 0.013, p = 0.016, p = 0.030 and p = 0.018 respectively).

Conclusions: Arterial inflammation is increased during TSH suppression. This finding sheds new light on the underlying mechanism of the suspected increased risk of cardiovascular disease in patients with TSH suppression.
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http://dx.doi.org/10.1007/s00259-019-04292-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533218PMC
July 2019

[Risk stratification and role for additional diagnostic testing in patients with acute chest pain and normal high-sensitivity cardiac troponin levels].

Ned Tijdschr Geneeskd 2018 12 5;162. Epub 2018 Dec 5.

Maastricht UMC+, afd. Cardiologie.

Background: Normal high sensitivity cardiac troponin (hs-cTn) assays rule out acute myocardial infarction (AMI) with great accuracy, but additional non-invasive testing is frequently ordered. This observational study evaluates whether clinical characteristics can contribute to risk stratification and could guide referral for additional testing.

Methods: This observational study included 918 patients with acute chest pain and normal hs-cTnT values. Major adverse cardiac events (MACE) and non-invasive test results were assessed during one-year follow-up. Patients were classified as low and high risk based on clinical characteristics.

Results: In total, 6,4% of patients experienced MACE during follow-up and mainly comprised revascularisations (86%). Absence of both recent abnormal stress test and suspicious history identified 86% of patients. These patients were at very low risk for MACE (0,4% in 30-days). Despite this, the majority (287/345=83%) of additional tests were performed in low risk patients, with 8% abnormal test findings (positive predictive value for MACE was 17%). The diagnostic yield was significantly higher in the remaining higher risk patients, 40% abnormal test findings and a positive predictive value of 70% for MACE.

Conclusion: Clinical characteristics can be used to identify low risk patients with acute chest pain and normal hs-cTnT levels. Current strategies in the emergency department result in numerous additional tests, which are mostly ordered in patients at very low risk and have a low diagnostic yield.
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December 2018

Risk stratification and role for additional diagnostic testing in patients with acute chest pain and normal high-sensitivity cardiac troponin levels.

PLoS One 2018 7;13(9):e0203506. Epub 2018 Sep 7.

Department of Cardiology, Maastricht University Medical Center, Maastricht, The Netherlands.

Background: Normal high sensitivity cardiac troponin (hs-cTn) assays rule out acute myocardial infarction (AMI) with great accuracy, but additional non-invasive testing is frequently ordered. This observational study evaluates whether clinical characteristics can contribute to risk stratification and could guide referral for additional testing.

Methods: 918 serial patients with acute chest pain and normal hs-cTnT levels were prospectively included. Major adverse cardiac events (MACE) and non-invasive test results were assessed during one-year follow-up. Patients were classified as low and high risk based on clinical characteristics.

Results: MACE occurred in 6.1% of patients and mainly comprised revascularizations (86%). A recent abnormal stress test, suspicious history, a positive family history and higher baseline hs-cTnT levels were independent predictors of MACE with odds ratios of 16.00 (95%CI:6.25-40.96), 16.43 (6.36-42.45), 2.33 (1.22-4.42) and 1.10 (1.01-1.21), respectively. Absence of both recent abnormal stress test and suspicious history identified 86% of patients. These patients were at very low risk for MACE (0.4% in 30-days and 2.3% in one-year). Despite this, the majority (287/345 = 83%) of additional tests were performed in low risk patients, with <10% abnormal test findings. The diagnostic yield was significantly higher in the remaining higher risk patients, 40% abnormal test findings and a positive predictive value of 70% for MACE. Similar results were observed in patients without known coronary artery disease.

Conclusions: Clinical characteristics can be used to identify low risk patients with acute chest pain and normal hs-cTnT levels. Current strategies in the emergency department result in numerous additional tests, which are mostly ordered in patients at very low risk and have a low diagnostic yield.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203506PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128560PMC
February 2019

Sex-Related Aspects of Biomarkers in Cardiac Disease.

Adv Exp Med Biol 2018;1065:545-564

Department of Clinical Chemistry, Central Diagnostic Laboratory, Maastricht University Medical Center, Maastricht, The Netherlands.

Biomarkers play an important role in the clinical management of cardiac care. In particular, cardiac troponins (cTn) and natriuretic peptides are the cornerstones for the diagnosis of acute myocardial infarction (AMI) and for the diagnosis of heart failure (HF), respectively. Current guidelines do not make a distinction between women and men. However, the commonly used "one size fits all" algorithms are topic of debate to improve assessment of prognosis, particularly in women. Due to the high-sensitivity assays (hs-cTn), lower cTn levels (and 99th percentile upper reference limits) were observed in women as compared with men. Sex-specific diagnostic thresholds may improve the diagnosis of AMI in women, though clinical relevance remains controversial and more trials are needed. Also other diagnostic aspects are under investigation, like combined biomarkers approach and rapid measurement strategies. For the natriuretic peptides, previous studies observed higher concentrations in women than in men, especially in premenopausal women who might benefit from the cardioprotective actions. Contrary to hs-cTn, natriuretic peptides are particularly incorporated in the ruling-out algorithms for the diagnosis of HF and not ruling-in. Clinical relevance of sex differences here seems marginal, as clinical research has shown that negative predictive values for ruling-out HF were hardly effected when applying a universal diagnostic threshold that is independent from sex or other risk factors. Apart from the diagnostic issues of AMI in women, we believe that in the future most sex-specific benefits of cardiac biomarkers can be obtained in patient follow-up (guiding therapy) and prognostic applications, fitting modern ideas on preventive and personalized medicine.
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http://dx.doi.org/10.1007/978-3-319-77932-4_33DOI Listing
March 2019

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

Circulation 2018 09;138(10):989-999

2nd Department of Cardiology and School of Medicine with the Division of Dentistry, Zabrze, Medical University of Katowice, Katowice, Poland (B.M., D.K.).

Background: Combining 2 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 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 acute myocardial infarction.

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 acute myocardial infarction. 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 European Society of Cardiology 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 European Society of Cardiology 2015 guideline recommended algorithms and cut-offs, the proportion meeting rule-out criteria after the baseline blood sampling was limited (6% to 24%) and assay dependent. Application of optimized cut-off values using the sum (9 ng/L) and product (18 ng/L) of hs-cTnI and hs-cTnT concentrations led to an increase in the proportion ruled-out after a single blood draw to 34% to 41% in the original (sum: negative predictive value [NPV] 100% [95% confidence interval (CI), 99.5% to 100%]; product: NPV 100% [95% CI, 99.5% to 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% to 43% ruled out; NPV original cohort 99.9% [95% CI, 99.2-100%]; NPV validation cohort 99.5% [95% CI, 98.9-99.8%]) and rule-in (positive predictive value [PPV] original cohort 74.4% [95% Cl, 69.6-78.8%]; PPV validation cohort 84.0% [95% Cl, 79.7-87.6%]).

Conclusions: New strategies combining hs-cTnI and hs-cTnT concentrations may significantly increase the number of patients eligible for very early and safe rule-out, but do not seem helpful for the rule-in of acute myocardial infarction.

Clinical Trial Registration: URL (APACE): https://www.clinicaltrial.gov . Unique identifier: NCT00470587. URL (ADAPT): www.anzctr.org.au . Unique identifier: ACTRN12611001069943.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.117.032003DOI Listing
September 2018

Cardiac Troponin T: Smaller Molecules in Patients with End-Stage Renal Disease than after Onset of Acute Myocardial Infarction.

Clin Chem 2017 03 10;63(3):683-690. Epub 2017 Jan 10.

Department of Clinical Chemistry, Central Diagnostic Laboratory, Maastricht University Medical Center.

Background: We have found previously that in acute myocardial infarction (AMI), cardiac troponin T (cTnT) is degraded in a time-dependent pattern. We investigated whether cTnT forms differed in patients with chronic cTnT increases, as seen with renal dysfunction, from those in the acute phase of myocardial infarction.

Methods: We separated cTnT forms by gel filtration chromatography (GFC) in end-stage renal disease (ESRD) patients: prehemodialysis (pre-HD) and post-HD (n = 10) and 2 months follow-up (n = 6). Purified (cTnT) standards, quality control materials of the clinical cTnT immunoassay (Roche), and AMI patients' sera also were analyzed. Immunoprecipitation and Western blotting were performed with the original cTnT antibodies from the clinical assay and antibodies against the N- and C-terminal end of cTnT.

Results: GFC analysis revealed the retention of purified cTnT at 27.5 mL, identical to that for cTnT in quality controls. For all ESRD patients, one cTnT peak was found at 45 mL, pre- and post-HD, and stable over time. Western blotting illustrated that this peak corresponded to cTnT fragments <18 kDa missing the N- and C-terminal ends. AMI patients' sera revealed cTnT peaks at 27.5 and 45 mL, respectively, corresponding to N-terminal truncated cTnT of 29 kDa and N- and C-terminal truncated fragments of <18 kDa, respectively.

Conclusions: We found that cTnT forms in ESRD patients are small (<18 kDa) and different from forms seen in AMI patients. These insights may prove useful for development of a more specific cTnT immunoassay, especially for the acute and diagnostic phase of myocardial infarction.
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http://dx.doi.org/10.1373/clinchem.2016.261644DOI Listing
March 2017

Acute chest pain in the high-sensitivity cardiac troponin era: A changing role for noninvasive imaging?

Am Heart J 2016 07 30;177:102-11. Epub 2016 Apr 30.

Department of Cardiology, Maastricht University Medical Center, Maastricht, the Netherlands; Cardiovascular Research Institute Maastricht (CARIM), School for Cardiovascular Diseases, Maastricht University Medical Center, Maastricht, the Netherlands. Electronic address:

Management of patients with acute chest pain remains challenging. Cardiac biomarker testing reduces the likelihood of erroneously discharging patients with acute myocardial infarction (AMI). Despite normal contemporary troponins, physicians have still been reluctant to discharge patients without additional testing. Nowadays, the extremely high negative predictive value of current high-sensitivity cardiac troponin (hs-cTn) assays challenges this need. However, the decreased specificity of hs-cTn assays to diagnose AMI poses a new problem as noncoronary diseases (eg, pulmonary embolism, myocarditis, cardiomyopathies, hypertension, renal failure, etc) may also cause elevated hs-cTn levels. Subjecting patients with noncoronary diseases to unnecessary pharmacological therapy or invasive procedures must be prevented. Attempts to improve the positive predictive value to diagnose AMI by defining higher initial cutoff values or dynamic changes over time inherently lower the sensitivity of troponin assays. In this review, we anticipate a potential changing role of noninvasive imaging from ruling out myocardial disease when troponin values are normal toward characterizing myocardial disease when hs-cTn values are (mildly) abnormal.
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http://dx.doi.org/10.1016/j.ahj.2016.03.025DOI Listing
July 2016

Cardiac Troponin T and I Release After a 30-km Run.

Am J Cardiol 2016 Jul 4;118(2):281-7. Epub 2016 May 4.

Department of Clinical Chemistry, Maastricht University Medical Center, Maastricht, the Netherlands; Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, the Netherlands. Electronic address:

Prolonged endurance-type exercise is associated with elevated cardiac troponin (cTn) levels in asymptomatic recreational athletes. It is unclear whether exercise-induced cTn release mirrors a physiological or pathological underlying process. The aim of this study was to provide a direct comparison of the release kinetics of high-sensitivity cTnI (hs-cTnI) and T (hs-cTnT) after endurance-type exercise. In addition, the effect of remote ischemic preconditioning (RIPC), a cardioprotective strategy that limits ischemia-reperfusion injury, was investigated in a randomized controlled crossover manner. Twenty-five healthy volunteers completed an outdoor 30-km running trial preceded by RIPC (4 × 5 min 220 mm Hg unilateral occlusion) or control intervention. hs-cTnT, hs-cTnI, and sensitive cTnI (s-cTnI) concentrations were examined before, immediately after, 2 and 5 hours after the trial. The completion of a 30-km run resulted in a significant increase in circulating cTn (time: all p <0.001), with maximum hs-cTnT, hs-cTnI, and s-cTnI levels of 47 ± 27, 69 ± 62, and 82 ± 64 ng/L (mean ± SD), respectively. Maximum hs-cTnT concentrations were measured in 60% of the participants at 2 hours after exercise, compared with maximum hs-cTnI and s-cTnI concentrations at 5 hours in 84% and 80% of the participants. Application of an RIPC stimulus did not reduce exercise-induced cTn release (time × trial: all p >0.5). In conclusion, in contrast to acute myocardial infarction, maximum hs-cTnT levels after exercise precede maximum hs-cTnI levels. Distinct release kinetics of hs-cTnT and hs-cTnI and the absence of an effect of RIPC favors the concept that exercise-induced cTn release may be mechanistically distinct from cTn release in acute myocardial infarction.
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http://dx.doi.org/10.1016/j.amjcard.2016.04.030DOI Listing
July 2016

High-Sensitivity Cardiac Troponin Concentrations in Patients with Chest Discomfort: Is It the Heart or the Kidneys As Well?

PLoS One 2016 20;11(4):e0153300. Epub 2016 Apr 20.

Central Diagnostic Laboratory, Department of Clinical Chemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center (MUMC+), Maastricht, the Netherlands.

Background: High-sensitivity cardiac troponins (hs-cTn) are the preferred biomarkers to detect myocardial injury, making them promising risk-stratifying tools for patients with symptoms of chest pain. However, circulating hs-cTn are also elevated in other conditions like renal dysfunction, complicating appropriate interpretation of low-level hs-cTn concentrations.

Methods: A cross-sectional analysis was performed in 1864 patients with symptoms of chest discomfort from the cardiology outpatient department who underwent cardiac computed tomographic angiography (CCTA). Serum samples were analyzed using hs-cTnT and hs-cTnI assays. Renal function was measured by the estimated glomerular filtration rate (eGFR), established from serum creatinine and cystatin C. On follow-up, the incidence of adverse events was assessed.

Results: Median hs-cTnT and hs-cTnI concentrations were 7.2(5.8-9.2) ng/L and 2.6(1.8-4.1) ng/L, respectively. Multivariable regression analysis revealed that both assay results were more strongly associated with eGFR (hs-cTnT:stβ:-0.290;hs-cTnI:stβ:-0.222) than with cardiac imaging parameters, such as coronary calcium score, CCTA plaque severity score and left ventricular mass (all p<0.01). Furthermore, survival analysis indicated lower relative risks in patients with normal compared to reduced renal function for hs-cTnT [HR(95%CI), 1.02(1.00-1.03) compared to 1.07(1.05-1.09)] and hs-cTnI [1.01(1.00-1.01) compared to 1.02(1.01-1.02)] (all p<0.001).

Conclusion: In patients with chest discomfort, we identified an independent influence of renal function on hs-cTn concentrations besides CAD, that affected the association of hs-cTn concentrations with adverse events. Estimating renal function is therefore warranted when interpreting baseline hs-cTn concentrations.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0153300PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4838230PMC
August 2016

Unstable coronary plaque characteristics are associated with high-sensitivity cardiac troponin T and N-terminal Pro-Brain Natriuretic Peptide.

J Cardiovasc Comput Tomogr 2016 Jan-Feb;10(1):82-8. Epub 2015 Oct 10.

Department of Cardiology, Maastricht University Medical Center (MUMC+), P. Debyelaan 25, PO Box 5800, 6202 AZ, Maastricht, The Netherlands; Cardiovascular Research Institute, School for Cardiovascular Diseases, P. Debyelaan 25, PO Box 5800, 6202 AZ, Maastricht, The Netherlands; Department of Radiology, MUMC+, P. Debyelaan 25, PO Box 5800, 6202 AZ, Maastricht, The Netherlands. Electronic address:

Background: Unstable plaque characteristics on coronary CT angiography (CTA), serum high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) concentrations are associated with cardiovascular events.

Objective: To investigate the association between coronary CTA defined quantifiable plaque characteristics, hs-cTnT and NT-proBNP.

Methods: 81 consecutive stable chest pain patients with an intermediate-to-high risk were analyzed. Coronary CTA was performed using a 64-slice multidetector-row CT-scanner. Total coronary plaque volume, calcified volume, non-calcified volume, plaque burden, remodeling index (RI) and number of plaques were measured using dedicated software. A total plaque score ("Sum plaque score") incorporating total plaque volume, RI, plaque burden and number of plaques was defined. Hs-cTnT and NT-proBNP concentrations were measured in serum samples before coronary CTA.

Results: Univariate regression analysis demonstrated significant associations of hs-cTnT and NT-proBNP with total plaque volume (r hs-cTnT = .256; r NT-proBNP = .270), calcified volume (r hs-cTnT = .344; r NT-proBNP = .344), RI (r hs-cTnT = .335; r NT-proBNP = .342) and number of plaques (r hs-cTnT = .355; r NT-proBNP = .301) (all P values ≤ .021). Non-calcified plaque volume showed no association with hs-cTnT and NT-proBNP (r hs-cTnT = .050; r NT-proBNP = .087; P value = .660 and P value = .442). The "Sum plaque score" showed the highest correlation compared to other plaque parameters (r hs-cTnT = .362; r NT-proBNP = .409; P value = .001 and P value ≤ .001).

Conclusion: Our data suggest that coronary plaque morphology parameters, derived by dedicated software, are associated with serum hs-cTnT and NT-proBNP concentrations.
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http://dx.doi.org/10.1016/j.jcct.2015.10.001DOI Listing
October 2016

Clinical Interpretation of Elevated Concentrations of Cardiac Troponin T, but Not Troponin I, in Nursing Home Residents.

J Am Med Dir Assoc 2015 Oct 6;16(10):884-91. Epub 2015 Aug 6.

Department of Clinical Chemistry, Central Diagnostic Laboratory and Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands. Electronic address:

Objective: Cardiac troponins T (cTnT) and I (cTnI) are the preferred biomarkers to detect myocardial damage. The present study explores the value of measuring cardiac troponins (cTn) in nursing home residents, by investigating its relation to heart failure and 1-year mortality using 1 cTnT and 2 cTnI assays that are widely used in clinical practice.

Design: All participants underwent extensive clinical examinations and echocardiographic assessment for the diagnosis of heart failure. cTn was measured using high-sensitive (hs)- cTnT (Roche), hs-cTnI (Abbott), and sensitive cTnI (Beckman) assays. The glomerular filtration rate was estimated (eGFR) using serum creatinine and cystatin C concentrations. Data on all-cause mortality were collected at 1-year follow-up.

Participants And Setting: Participants were 495 long-term nursing home residents, older than 65 years, of 5 Dutch nursing home organizations.

Results: Median (IQR) concentrations were 20.6 (17.8-30.6), 6.8 (4.1-12.5), and 4.0 (2.0-8.0) ng/L for hs-cTnT, hs-cTnI, and cTnI, respectively. In total, 79% had elevated hs-cTnT concentrations, whereas only 9% and 5% of hs-cTnI and cTnI concentrations were elevated. Most important and independent determinants for higher hs-cTnT and hs-cTnI concentrations were heart failure and renal dysfunction. Whereas both heart failure (odds ratio [OR] 3.4) and eGFR lower than 60 mL/min/1.73 m(2) (OR 3.6) were equal contributors to higher hs-cTnT concentrations (all P < .001), hs-cTnI and cTnI were less associated with renal dysfunction (OR of, respectively, 1.9 and 2.1; P < .01) in comparison with heart failure (OR 4.3 and 4.7, respectively, P < .001). Furthermore, residents with higher hs-cTnT or hs-cTnI concentrations (fourth quartile) had respectively 4 versus 2 times more risk of 1-year mortality compared with lower concentrations.

Conclusion: Regardless of their cardiac health, hs-cTnT but not hs-cTnI concentrations were elevated in almost all aged nursing home residents, questioning the use of the current diagnostic cutoff in elderly with high comorbidity. Nonetheless, measuring cardiac troponins, especially hs-cTnT, had a promising role in assessing future risk of mortality.
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http://dx.doi.org/10.1016/j.jamda.2015.06.026DOI Listing
October 2015

Influence of contrast media viscosity and temperature on injection pressure in computed tomographic angiography: a phantom study.

Invest Radiol 2014 Apr;49(4):217-23

From the *Department of Radiology, †CARIM School for Cardiovascular Diseases, Departments of ‡Clinical Chemistry, and §Cardiology, Maastricht University Medical Center, Maastricht, The Netherlands; Departments of ∥Neuroradiology, and ¶Nuclear Medicine, University Hospital RWTH Aachen, Aachen, Germany.

Purpose: Iodinated contrast media (CM) in computed tomographic angiography is characterized by its concentration and, consecutively, by its viscosity. Viscosity itself is directly influenced by temperature, which will furthermore affect injection pressure. Therefore, the purposes of this study were to systematically evaluate the viscosity of different CM at different temperatures and to assess their impact on injection pressure in a circulation phantom.

Materials And Methods: Initially, viscosity of different contrast media concentrations (240, 300, 370, and 400 mgI/mL) was measured at different temperatures (20°C-40°C) with a commercially available viscosimeter. In the next step, a circulation phantom with physical conditions was used. Contrast media were prepared at different temperatures (20°C, 30°C, 37°C) and injected through a standard 18-gauge needle. All other relevant parameters were kept constant (iodine delivery rate, 1.9 g I/s; total amount of iodine, 15 g I). Peak flow rate (in milliliter per second) and injection pressure (psi) were monitored. Differences in significance were tested using the Kruskal-Wallis test (Statistical Package for the Social Sciences).

Results: Viscosities for iodinated CM of 240, 300, 370, and 400 mg I/mL at 20°C were 5.1, 9.1, 21.2, and 28.8 mPa.s, respectively, whereas, at 40°C, these were substantially lower (2.8, 4.4, 8.7, and 11.2 mPa.s). In the circulation phantom, mean (SD) peak pressures for CM of 240 mg I/mL at 20°C, 30°C, and 37°C were 107 (1.5), 95 (0.6), and 92 (2.1) psi; for CM of 300 mg I/mL, 119 (1.5), 104 (0.6), and 100 (3.6) psi; for CM of 370 mg I/mL, 150 (0.6), 133 (4.4), and 120 (3.5) psi; and for CM of 400 mg I/mL, 169 (1.0), 140 (2.1), and 135 (2.9) psi, respectively, with all P values less than 0.05.

Conclusions: Low concentration, low viscosity, and high temperatures of CM are beneficial in terms of injection pressure. This should also be considered for individually tailored contrast protocols in daily routine scanning.
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http://dx.doi.org/10.1097/RLI.0000000000000019DOI Listing
April 2014

The role of cardiovascular magnetic resonance imaging and computed tomography angiography in suspected non-ST-elevation myocardial infarction patients: design and rationale of the CARdiovascular Magnetic rEsoNance imaging and computed Tomography Angiography (CARMENTA) trial.

Am Heart J 2013 Dec 23;166(6):968-75. Epub 2013 Oct 23.

Department of Cardiology, Maastricht University Medical Center, Maastricht, The Netherlands; Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands.

Background: Although high-sensitivity cardiac troponin (hs-cTn) substantially improves the early detection of myocardial injury, it lacks specificity for acute myocardial infarction (MI). In suspected non-ST-elevation MI, invasive coronary angiography (ICA) remains necessary to distinguish between acute MI and noncoronary myocardial disease (eg, myocarditis), unnecessarily subjecting the latter to ICA and associated complications. This trial investigates whether implementing cardiovascular magnetic resonance (CMR) or computed tomography angiography (CTA) early in the diagnostic process may help to differentiate between coronary and noncoronary myocardial disease, thereby preventing unnecessary ICA.

Study Design: In this prospective, single-center, randomized controlled clinical trial, 321 consecutive patients with acute chest pain, elevated hs-cTnT, and nondiagnostic electrocardiogram are randomized to 1 of 3 strategies: (1) CMR, or (2) CTA early in the diagnostic process, or (3) routine clinical management. In the 2 investigational arms of the study, results of CMR or CTA will guide further clinical management. It is expected that noncoronary myocardial disease is detected more frequently after early noninvasive imaging as compared with routine clinical management, and unnecessary ICA will be prevented. The primary end point is the total number of patients undergoing ICA during initial admission. Secondary end points are 30-day and 1-year clinical outcome (major adverse cardiac events and major procedure-related complications), time to final diagnosis, quality of life, and cost-effectiveness.

Conclusion: The CARMENTA trial investigates whether implementing CTA or CMR early in the diagnostic process in suspected non-ST-elevation MI based on elevated hs-cTnT can prevent unnecessary ICA as compared with routine clinical management, with no detrimental effect on clinical outcome.
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http://dx.doi.org/10.1016/j.ahj.2013.09.012DOI Listing
December 2013

Time-dependent degradation pattern of cardiac troponin T following myocardial infarction.

Clin Chem 2013 Jul 27;59(7):1083-90. Epub 2013 Mar 27.

Department of Clinical Chemistry, Maastricht University Medical Center, the Netherlands.

Background: Cardiac troponin T (cTnT) is widely used for the diagnosis of acute myocardial infarction (AMI). However, it is still unclear whether degraded cTnT forms circulate in the patient's blood. We therefore aimed to elucidate which cTnT forms are detected by the clinical assay.

Methods: Separation of cTnT forms by gel filtration chromatography (GFC) was performed in sera from 13 AMI patients to examine cTnT degradation. The GFC eluates were subjected to Western blot analysis with the original antibodies from the Roche immunoassay used to mimic the clinical cTnT assay. To investigate the degradation pattern with time, standardized serum samples of 18 AMI patients collected 0-72 h after admission were analyzed by Western blot analysis.

Results: GFC analysis of AMI patients' sera revealed 2 cTnT peaks with retention volumes of 5 and 21 mL. Western blot analysis identified these peaks as cTnT fragments of 29 and 14-18 kDa, respectively. Furthermore, the performance of direct Western blots on standardized serum samples demonstrated a time-dependent degradation pattern of cTnT, with fragments ranging between 14 and 40 kDa. Intact cTnT (40 kDa) was present in only 3 patients within the first 8 h after hospital admission.

Conclusions: These results demonstrate that the Roche cTnT immunoassay detects intact as well as degraded cTnT forms in AMI patients' sera during the period of diagnostic testing. Moreover, following AMI, cTnT is degraded in a time-dependent pattern.
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http://dx.doi.org/10.1373/clinchem.2012.200543DOI Listing
July 2013

[Cardiac troponin].

Ned Tijdschr Geneeskd 2012 ;156(42):A5044

Afd. Klinische chemie, Maastricht Universitair Medisch Centrum, Maastricht, the Netherlands.

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 very recently been established. We describe two male patients who presented at the emergency department with acute chest pain, but in whom clear evidence for a myocardial infarction in the ST segment of the EKG was lacking. Case 1 illustrates that such assays enable the earlier diagnosis of acute myocardial infarction. Case 2 shows that the diagnosis of acute myocardial infarction should be accompanied by a typical rise or fall of troponin concentrations. The latest insights into high-sensitivity cardiac troponin assays are discussed in this article. We focus specifically on sensitivity and specificity, reference values obtained from a healthy control group, and the reference change value required to detect acute myocardial infarction.
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December 2012
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