Identification of macrotroponin T: findings from a case report and non-reproducible troponin T results

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Leo Lam ◽  
Leah Ha ◽  
Campbell Heron ◽  
Weldon Chiu ◽  
Campbell Kyle
Keyword(s):  
Troponin T ◽  
Protein A ◽  
Cardiac Injury ◽  
High Sensitivity ◽  
High Molecular Weight Complex ◽  
High Incidence ◽  
Laboratory Results ◽  
Clinical Consequences ◽  
Very High ◽  
Biochemical Features

Abstract Objectives Macrotroponin is due to cardiac troponin (cTn) binding to endogenous cTn autoantibodies. While previous studies showed a high incidence of macrotroponin affecting cTnI assays, reports of macrotroponin T, particularly without cTnI reactivity, have been rare. Although the clinical significance of macrotroponin is not fully understood, macroenzymes and complexes are recognised to cause confusion in interpretation of laboratory results. The potential for adverse clinical consequences due to misinterpretation of affected results is very high. Methods We describe four cases of macrotroponin T with persistently low high sensitivity cTnT (hs-cTnT) by the 9 min compared to the 18 min variant of the assay. Three cases were serendipitously identified due to the use of a lot number of Roche hs-cTnT affected by non-reproducible results, necessitating measurement of cTnT in duplicate. We identified and characterised these macrotroponin specimens by immunoglobulin depletion (Protein A and PEG precipitation), mixing studies with EDTA and recombinant cTnT. Results In cases of macro-cTnT, a lower result occurred on the hs-cTnT using the 9 min compared to 18 min variant assay (ratio of 9–18 min hs-cTnT <0.80). Mixing studies with recombinant cTnT or EDTA demonstrated a difference in recovery vs. controls. One of these patients demonstrated a high molecular weight complex for cTnI and cTnT demonstrating a macrocomplex involving both cTn. This patient demonstrated a rise and fall in cTn when measured by several commercial assays consistent with genuine acute cardiac injury. Conclusions We identified several cases of macro-cTnT and described associated clinical and biochemical features.

High incidence of macrotroponin I with a high-sensitivity troponin I assay

2016 ◽  
Vol 54 (11) ◽  
Author(s):  
Janet V. Warner ◽  
George A. Marshall
Keyword(s):  
Myocardial Injury ◽  
Troponin I ◽  
Protein A ◽  
Gel Filtration ◽  
High Sensitivity ◽  
Systematic Investigation ◽  
Clinical Samples ◽  
High Molecular Weight Complex ◽  
High Sensitivity Troponin ◽  
High Sensitive Troponin

AbstractBackground:Cardiac troponin is the preferred biomarker of myocardial injury. High-sensitivity troponin assays allow measurement of very low levels of troponin with excellent precision. After the introduction of a high-sensitivity troponin I assay the laboratory began to receive enquiries from clinicians about clinically discordant elevated troponin I results. This led to a systematic investigation and characterisation of the cause.Methods:Routine clinical samples were measured by the Architect High Sensitive Troponin-I (hsTnI) and the VITROS Troponin I ES assays (VitrosTnI). Results that were elevated according to the Architect but not the VITROS assay (Group 1) or results elevated by both assays but disproportionately higher on the Architect (Group 2) were re-analysed for hsTnI after re-centrifugation, multiple dilutions, incubation with heterophilic blocking reagents, polyethylene glycol (PEG) precipitation, and Protein A/G/L treatment. Sephacryl S-300 HR gel filtration chromatography (GFC) was performed on selected specimens.Results:A high molecular weight complex containing immunoreactive troponin I and immunoglobulin (macrotroponin I) was identified in 5% of patients with elevated hsTnI. Patients with both macrotroponin and myocardial injury had higher and longer elevation of hsTnI compared with VitrosTnI with peaks of both macrotroponin and free troponin I-C complex on GFC.Conclusions:Circulating macrotroponin I (macroTnI) causes elevated hsTnI results with the Architect High Sensitive Troponin-I assay with the potential to be clinically misleading. The assay involved in this investigation may not be the only assay affected by macrotroponin. It is important for laboratories and clinicians to be aware of and develop processes to identify and manage specimens with elevated results due to macrotroponin.

scholarly journals Diagnostic and Prognostic Information Provided by a High Sensitivity Assay for Cardiac Troponin T

2010 ◽  
Vol 29 (4) ◽  
pp. 274-281 ◽  
Author(s):  
Jochen Jarausch
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Troponin ◽  
Troponin T ◽  
Cardiac Injury ◽  
High Sensitivity ◽  
Recent Experience ◽  
Cardiac Troponin T ◽  
Prognostic Information ◽  
Coronary Syndrome ◽  
Number Of Patients

Diagnostic and Prognostic Information Provided by a High Sensitivity Assay for Cardiac Troponin TCardiac troponins (cTns) are the preferred biomarkers for the diagnosis of acute myocardial infarction, assessment of risk and prognosis, and for determination of antithrombotic and revascularization strategy in patients with acute coronary syndromes. The implementation of high sensitivity cTn assays into the clinical routine has increased the number of patients diagnosed with myocardial infarction. In addition, the number of patients with elevated cTn levels that cannot be explained by acute ischemic injury was increased, which is observed in patients with chronic heart disease and other nonischemic cardiac injury or in patients with impaired renal function. The new definition of myocardial infarction provides support for the interpretation of elevated cTn measured with high sensitivity cTn assays in patients with suspected acute coronary syndrome. This review will summarize clinical studies with the recently introduced high sensitivity cTnT assay (TnT hs) with reference to recent experience with high sensitivity cTn assays in general.

scholarly journals The relationship between cardiac injury, inflammation and coagulation in predicting COVID-19 outcome

2020 ◽  
Author(s):  
Alessandro Mengozzi ◽  
Georgios Georgiopoulos ◽  
Marco Falcone ◽  
Giusy Tiseo ◽  
Nicola Riccardo Pugliese ◽  
...  
Keyword(s):  
Troponin T ◽  
Strong Predictor ◽  
Cardiac Injury ◽  
High Sensitivity ◽  
Strong Relationship ◽  
High Sensitivity Troponin T ◽  
The Relationship ◽  
D Dimer ◽  
Related Mortality

Abstract Introduction: High sensitivity troponin T (hsTnT) is a strong predictor of adverse outcome during SARS-CoV-2 infection. However, its determinants remain partially unknown. We aimed to assess the relationship between severity of inflammatory response/coagulation abnormalities and hsTnT in Coronavirus Disease 2019 (COVID-19). We then explored the relevance of these pathways in defining mortality and complications risk and the potential effects of the treatments to attenuate such risk.Methods: In this single-center, prospective, observational study we enrolled 266 consecutive patients hospitalized for SARS-CoV-2 pneumonia. Primary endpoint was in-hospital COVID-19 mortality. Results: hsTnT, even after adjustment for confounders, was associated with mortality. D-dimer and CRP presented stronger associations with hsTnT than PaO2. Changes of hsTnT, D-dimer and CRP were related but only D-dimer was associated with mortality. Moreover, low molecular weight heparin showed attenuation of the mortality in the whole population, particularly in subjects with higher hsTnT.Conclusions: D-dimer possessed a strong relationship with hsTnT and mortality. Anticoagulation treatment showed greater benefits with regard to mortality. These findings suggest a major role of SARS-CoV-2 coagulopathy in hsTnT elevation and its related mortality in COVID-19. A better understanding of the mechanisms related to COVID-19 might pave the way to therapy tailoring in these high-risk individuals.

scholarly journals Severe Acute Respiratory Syndrome Coronavirus 2: The Importance of Prompt Detection of Cardiovascular Involvement

2020 ◽  
Vol 14 (1) ◽  
pp. 38-41
Author(s):  
Osmar A. Centurión ◽  
Luís M. Miño ◽  
Karina E. Scavenius
Keyword(s):  
Troponin T ◽  
Cardiac Injury ◽  
High Sensitivity ◽  
Protein Levels ◽  
Reactive Protein ◽  
Appropriate Treatment ◽  
Cardiovascular Involvement ◽  
Positive Linear Correlation ◽  
Clinical Surveillance ◽  
Myocardial Involvement

Increased morbidity and mortality are associated with coronavirus disease 2019 (COVID-19) when there is cardiovascular (CV) involvement. Due to the absence of prospective, well-designed, controlled studies, the exact mechanism responsible for cardiac injury among patients with COVID-19 remains uncertain. However, possible mechanisms described in observational studies can be considered. Non-ischemic events and ischemic myocardial involvement are the two main pathophysiological mechanisms of acute cardiac injury in COVID-19 patients. Non-ischemic myocardial injury is probably predominant and is secondary to multiple pathological mechanisms. Cardiac involvement is relatively common among hospitalized patients with COVID-19 and is associated with a greater risk of in-hospital mortality and ventricular arrhythmias. There was also a high and significantly positive linear correlation between troponin T and plasma high-sensitivity C-reactive protein levels. It is important to promptly detect CV involvement to avoid increased mortality in these patients. These findings highlight the importance of clinical surveillance and laboratory testing of serum troponin levels to ensure appropriate early identification and proceed with appropriate treatment. This should apply to patients with/without prior CV involvement. There are several possible mechanisms of myocardial tissue damage and the exact mechanisms involved need to be explored in well-designed studies.

scholarly journals Overcoming Heparin-Associated RT-qPCR Inhibition and Normalization Issues for microRNA Quantification in Patients with Acute Myocardial Infarction

2018 ◽  
Vol 118 (07) ◽  
pp. 1257-1269 ◽  
Author(s):  
Jose Coelho-Lima ◽  
Ashfaq Mohammed ◽  
Suzanne Cormack ◽  
Samuel Jones ◽  
Rajiv Das ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Troponin T ◽  
Cardiac Injury ◽  
High Sensitivity ◽  
Sample Treatment ◽  
Heparin Administration ◽  
Screening Platform ◽  
Qpcr Normalization

Background Cardiac-enriched micro ribonucleic acids (miRNAs) are released into the circulation following ST-elevation myocardial infarction (STEMI). Lack of standardized approaches for reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) data normalization and presence of RT-qPCR inhibitors (e.g. heparin) in patient blood samples have prevented reproducible miRNA quantification in this cohort and subsequent translation of these biomarkers to clinical practice. Materials and Methods Using a RT-qPCR miRNA screening platform, we identified and validated an endogenous circulating miRNA as a normalization control. In addition, we assessed the effects of in vivo and in vitro anticoagulant drugs administration (heparin and bivalirudin) on three RT-qPCR normalization strategies (global miRNA mean, exogenous spike-in control [cel-miR-39] and endogenous miRNA control). Finally, we evaluated the effect of heparin and its in vitro inhibition with heparinase on the quantification of cardiac-enriched miRNAs in STEMI patients. Results miR-425–5p was validated as an endogenous miRNA control. Heparin administration in vitro and in vivo inhibited all RT-qPCR normalization strategies. In contrast, bivalirudin had no effects on cel-miR-39 or miR-425–5p quantification. In vitro RNA sample treatment with 0.3 U of heparinase overcame heparin-induced over-estimation of cardiac-enriched miRNA levels and improved their correlation with high-sensitivity troponin T. Conclusion miRNA quantification in STEMI patients receiving heparin is jeopardized by its effect on all RT-qPCR normalization approaches. Use of samples from bivalirudin-treated patients or in vitro treatment of heparin-contaminated samples with heparinase are suitable alternatives for miRNA quantification in this cohort. Finally, we reinforce the evidence that cardiac-enriched miRNAs early after myocardial reperfusion reflect the severity of cardiac injury.

248Real-world Outcome of the ESC 0/1-hour Algorithm when Routinely Applied in Early Presenters

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
R Twerenbold ◽  
J P Costabel ◽  
R Campos ◽  
R Arbucci ◽  
T Nestelberger ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Real World ◽  
Cardiac Troponin ◽  
Troponin T ◽  
Clinical Care ◽  
High Sensitivity ◽  
Outpatient Management ◽  
Late Presenters ◽  
Very High ◽  
Rule Out

Abstract Background The European Society of Cardiology (ESC) recommends the use of a 0/1h-algorithm for rapid triage of patients with suspected non-ST-elevation myocardial infarction (NSTEMI) using high-sensitivity cardiac troponin (hs-cTn). Concerns were articulated about its efficacy and particularly safety when applied in patients presenting early (≤3 hours) after chest pain onset, as hs-cTn concentrations might still be very low or even undetectable in these high-risk patients. Purpose We aimed to assess the real-world effectiveness, efficacy, and ultimately safety of the ESC 0/1h-algorithm when routinely applied in early presenters. Methods In a prospective international multicenter study enrolling unselected patients presenting with suspected NSTEMI to the ED, patients were assessed according to the ESC 0/1h-algorithm using high-sensitivity cardiac troponin T embedded in routine clinical care. Patients with ST-segment elevation myocardial infarctions were excluded. Safety was quantified by the 30-day incidence of major adverse cardiac events (MACE, defined as the composite of cardiovascular death and myocardial infarction including the index event) in the rule-out group and in outpatients. Results Among 2296 patients, 819 (36%) were early presenters. NSTEMI prevalence in early presenters was 11%. Effectiveness was very high as 97% of patients triaged towards rule-out by the ESC 0/1h-algorithm did not require additional cardiac investigations including hs-cTnT measurements at later time points (e.g. 3–12h) or coronary CT-angiography in the ED. Median time to discharge or transfer from the ED was 150 minutes [q1130, q3215]. Efficacy of the ESC 0/1h-algorithm was very high: 67% of patients were triaged towards rule-out and 14% towards rule-in of NSTEMI. Overall, 75% of early presenters underwent outpatient management. Safety of rule-out and outpatient management were excellent in early presenters with a 30-day MACE incidence of both 0% and comparable with 0.3% and 0.1% in late presenters, respectively (p=ns). Conclusions These real-world data document for the first time the excellent effectiveness, efficacy and particularly safety of the ESC 0/1h-algorithm when routinely applied in early presenters. No differences in safety could be observed when compared with late presenters.

scholarly journals Relationship Between Myocardial Injury During Index Hospitalization for SARS‐CoV‐2 Infection and Longer‐Term Outcomes

2021 ◽  
Author(s):  
Brittany Weber ◽  
Hasan Siddiqi ◽  
Guohai Zhou ◽  
Jefferson Vieira ◽  
Andy Kim ◽  
...  
Keyword(s):  
Cardiac Troponin ◽  
Myocardial Injury ◽  
Troponin T ◽  
Cardiac Injury ◽  
High Sensitivity ◽  
Cardiac Biomarkers ◽  
Study Cohort ◽  
Cardiac Troponin T ◽  
Index Hospitalization ◽  
The Relationship

Background Myocardial injury in patients with COVID‐19 is associated with increased mortality during index hospitalization; however, the relationship to long‐term sequelae of SARS‐CoV‐2 is unknown. This study assessed the relationship between myocardial injury (high‐sensitivity cardiac troponin T level) during index hospitalization for COVID‐19 and longer‐term outcomes. Methods and Results This is a prospective cohort of patients who were hospitalized at a single center between March and May 2020 with SARS‐CoV‐2. Cardiac biomarkers were systematically collected. Outcomes were adjudicated and stratified on the basis of myocardial injury. The study cohort includes 483 patients who had high‐sensitivity cardiac troponin T data during their index hospitalization. During index hospitalization, 91 (18.8%) died, 70 (14.4%) had thrombotic complications, and 126 (25.6%) had cardiovascular complications. By 12 months, 107 (22.2%) died. During index hospitalization, 301 (62.3%) had cardiac injury (high‐sensitivity cardiac troponin T≧14 ng/L); these patients had 28.6%, 32.2%, and 33.2% mortality during index hospitalization, at 6 months, and at 12 months, respectively, compared with 4.1%, 4.9%, and 4.9% mortality for those with low‐level positive troponin and 0%, 0%, and 0% for those with undetectable troponin. Of 392 (81.2%) patients who survived the index hospitalization, 94 (24%) had at least 1 readmission within 12 months, of whom 61 (65%) had myocardial injury during the index hospitalization. Of 377 (96%) patients who were alive and had follow‐up after the index hospitalization, 211 (56%) patients had a documented, detailed clinical assessment at 6 months. A total of 78 of 211 (37.0%) had ongoing COVID‐19–related symptoms; 34 of 211 (16.1%) had neurocognitive decline, 8 of 211 (3.8%) had increased supplemental oxygen requirements, and 42 of 211 (19.9%) had worsening functional status. Conclusions Myocardial injury during index hospitalization for COVID‐19 was associated with increased mortality and may predict who are more likely to have postacute sequelae of COVID‐19. Among patients who survived their index hospitalization, the incremental mortality through 12 months was low, even among troponin‐positive patients.

scholarly journals Optimizing Early Rule-Out Strategies for Acute Myocardial Infarction: Utility of 1-Hour Copeptin

2015 ◽  
Vol 61 (12) ◽  
pp. 1466-1474 ◽  
Author(s):  
Petra Hillinger ◽  
Raphael Twerenbold ◽  
Cedric Jaeger ◽  
Karin Wildi ◽  
Tobias Reichlin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Cardiac Troponin ◽  
Troponin T ◽  
High Sensitivity ◽  
Final Diagnosis ◽  
Intermediate Risk ◽  
Incremental Value ◽  
Very High ◽  
Rule Out

Abstract BACKGROUND Combined testing of high-sensitivity cardiac troponin T (hs-cTnT) and copeptin at presentation provides a very high—although still imperfect—negative predictive value (NPV) for the early rule-out of acute myocardial infarction (AMI). We hypothesized that a second copeptin measurement at 1 h might further increase the NPV. METHODS In a prospective diagnostic multicenter study, we measured hs-cTnT and copeptin concentrations at presentation and at 1 h in 1439 unselected patients presenting to the emergency department with suspected AMI. The final diagnosis was adjudicated by 2 independent cardiologists blinded to copeptin concentrations. We investigated the incremental value of 1-h copeptin in the rule-out setting (0-h hs-cTnT negative and 0-h copeptin negative) and the intermediate-risk setting (0-h hs-cTnT negative and 0-h copeptin positive). RESULTS The adjudicated diagnosis was AMI in 267 patients (18.6%). For measurements obtained at presentation, the NPV in the rule-out setting was 98.6% (95% CI, 97.4%–99.3%). Whereas 1-h copeptin did not increase the NPV significantly, 1-h hs-cTnT did, to 99.6% (95% CI, 98.7%–99.9%, P = 0.008). Similarly, in the intermediate-risk setting (NPV 92.8%, 95% CI, 88.7%–95.8%), 1-h copeptin did not significantly increase the NPV (P = 0.751), but 1-h hs-cTnT did, to 98.6 (95% CI, 96%–99.7%, P &lt; 0.001). CONCLUSIONS One-hour copeptin increased neither the safety of the rule-out process nor the NPV in the intermediate-risk setting. In contrast, the incremental value of 1-h hs-cTnT was substantial in both settings. ClinicalTrials.gov/NCT00470587

Diagnosis of acute myocardial infarction in patients with renal insufficiency using high-sensitivity troponin T

2015 ◽  
Vol 53 (5) ◽  
Author(s):  
Hualan Huang ◽  
Shuai Zhu ◽  
Weiqing Wang ◽  
Hong Yi ◽  
Xiangyang Du ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Renal Insufficiency ◽  
Troponin T ◽  
High Sensitivity ◽  
Final Diagnosis ◽  
St Segment Elevation ◽  
St Segment ◽  
High Incidence ◽  
High Sensitivity Troponin T

AbstractThe objective of this study was to examine the diagnostic accuracy of high-sensitivity cardiac troponin T (hs-cTnT) for acute myocardial infarction (AMI) in patients with renal insufficiency, since this population has a high incidence of non-AMI elevations of hs-cTnT.In this prospective study, we enrolled 2249 consecutive patients presenting with chest pain in the emergency department (ED), of whom 19.5% had an estimated glomerular filtration rate (eGFR)Of the patients, 1108 (49.3%) were diagnosed as having AMI [321 with non-ST segment elevation myocardial infarction (NSTEMI)]. In patients whose final diagnosis was not AMI, there was a low but significant correlation between hs-cTnT and renal function [eGFRUsing a higher hs-cTnT cut-off value based on eGFR level is necessary for accurate diagnosis of AMI or NSTEMI in patients with renal insufficiency.

Sign in / Sign up

Export Citation Format

Share Document