scholarly journals Spiegelmer-Based Sandwich Assay for Cardiac Troponin I Detection

2020 ◽  
Vol 21 (14) ◽  
pp. 4963 ◽  
Author(s):  
Zoltán János Tolnai ◽  
Judit András ◽  
Zsuzsanna Szeitner ◽  
Krisztina Percze ◽  
László Ferenc Simon ◽  
...  

Two subunits of the ternary troponin complex, I and C, have cardiac muscle specific isoforms, and hence could be applied as highly-selective markers of acute coronary syndrome. We aimed at paving the way for the development of a robust cardiac troponin I-detecting sandwich assay by replacing antibodies with nuclease resistant aptamer analogues, so-called spiegelmers. To complement the previously generated spiegelmers that were specific for the N-terminus of cTnI, spiegelmers were selected for an amino acid stretch in the proximity of the C-terminal part of the protein by using a D-amino acid composed peptide. Following the selection, the oligonucleotides were screened by filter binding assay, and surface plasmon resonance analysis of the most auspicious candidates demonstrated that this approach could provide spiegelmers with subnanomolar dissociation constant. To demonstrate if the selected spiegelmers are functional and suitable for cTnI detection in a sandwich type arrangement, AlphaLisa technology was leveraged and the obtained results demonstrated that spiegelmers with different epitope selectivity are suitable for specific detection of cTnI protein even in human plasma containing samples. These results suggest that spiegelmers could be considered in the development of the next generation cTnI monitoring assays.

2009 ◽  
Vol 55 (1) ◽  
pp. 85-92 ◽  
Author(s):  
Kai M Eggers ◽  
Allan S Jaffe ◽  
Lars Lind ◽  
Per Venge ◽  
Bertil Lindahl

Abstract Background: The aim of this study was to evaluate factors influencing the 99th percentile for cardiac troponin I (cTnI) when this cutoff value is established on a highly sensitive assay, and to compare the value of this cutoff to that of lower cutoffs in the prognostic assessment of patients with coronary artery disease. Methods: We used the recently refined Access AccuTnI assay (Beckman-Coulter) to assess the distribution of cTnI results in a community population of elderly individuals [PIVUS (Prospective Study of the Vasculature in Uppsala Seniors) study; n = 1005]. The utility of predefined cTnI cutoffs for risk stratification was then evaluated in 952 patients from the FRISC II (FRagmin and Fast Revascularization during InStability in Coronary artery disease) study at 6 months after these patients had suffered acute coronary syndrome. Results: Selection of assay results from a subcohort of PIVUS participants without cardiovascular disease resulted in a decrease of the 99th percentile from 0.044 μg/L to 0.028 μg/L. Men had higher rates of cTnI elevation with respect to the tested thresholds. Whereas the 99th percentile cutoff was not found to be a useful prognostic indicator for 5-year mortality, both the 90th percentile (hazard ratio 3.1; 95% CI 1.9–5.1) and the 75th percentile (hazard ratio 2.8; 95% CI 1.7–4.7) provided useful prognostic information. Sex-specific cutoffs did not improve risk prediction. Conclusions: The 99th percentile of cTnI depends highly on the characteristics of the reference population from which it is determined. This dependence on the reference population may affect the appropriateness of clinical conclusions based on this threshold. However, cTnI cutoffs below the 99th percentile seem to provide better prognostic discrimination in stabilized acute coronary syndrome patients and therefore may be preferable for risk stratification.


QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Sherif Farouk Ibrahim ◽  
Ashraf Elsayed Elagmy ◽  
Abdelrhman Gamal Abdelsabour

Abstract Background Sepsis is heterogenous with regard to factors such as causal microorganism, patient predisposition, co-morbidity and response to therapy, a key element and unifying feature is the manifestation of cardiovascular dysfunction. Elevated concentrations of cardiac troponin I (cTnI) are frequently observed in patients with severe sepsis and septic shock even in the absence of an acute coronary syndrome (ACS). Objective To evaluate the prognostic value of (cTnI) with echocardiography assessment in septic patients. Patients and Methods This study was conducted at the intensive care units of Ain Shams university hospitals. 20 patients of both sexes with age ranging from 18 to 70 years diagnosed with sepsis admitted to Intensive care unit were included in prospective observational study. Results Baseline cTnI had a significant positive correlation with follow up troponine (p = 0.0016). Baseline EF had a significant negative correlation with follow up troponine (p = 0.036). Using ROC-curve analysis, troponin level at a cutoff point (>1.9) predicted patients with mortality, with good (87%) accuracy, sensitivity= 90% and specificity= 90% (p < 0.01). Conclusion Elevated concentrations of cardiac troponin I (cTnI) are frequently observed in patients with sepsis and septic shock even in the absence of an acute coronary syndrome.


2019 ◽  
Vol 12 (1) ◽  
pp. 24-29
Author(s):  
Mohammad Jakir Hossain ◽  
Khondoker Asaduzzaman ◽  
Solaiman Hossain ◽  
Muhammad Badrul Alam ◽  
Nur Hossain

Background: In the diagnosis of acute coronary syndrome, cardiac troponin I is highly reliable and widely available biomarker. Serum level of cardiac troponin I is related to amount of myocardial damage and also closely relates to infarct size. Our aim of the study is to find out the relationship between cardiac troponin I and left ventricular systolic function after acute coronary syndrome. Methods: Total of 132 acute coronary syndrome patients were included in this study after admission in coronary care unit of Sir Salimullah Medical College, Mitford Hospital. Troponin I level was measured at admission and left ventricular ejection fraction (LVEF) was measured by echocardiography between 12-48 hours of onset of chest pain. Results: There was negative correlation between Troponin I at 12 to 48 hours of chest pain with LVEF in these study patients. With a cutoff value of troponin I e”6.8 ng/ml in STEMI patients there is a significant negative relation between 12 to 48 hrs troponin I and LVEF (p<0.001). Sensitivity of troponin I e” 6.8 ng/ml between 12 to 48 hours of chest pain in predicting LVEF <50% in STEMI was 93.75% and specificity was 77.78%. In NSTEMI sensitivity of troponin I e” 4.5 ng/ml between 12 to 48 hours of chest pain in predicting LVEF <50% was 65% and specificity was 54.05%. Conclusion: Serum troponin I level had a strong negative correlation with left ventricular ejection fraction after acute coronary syndrome and hence can be used to predict the LVEF in this setting. Cardiovasc. j. 2019; 12(1): 24-29


2014 ◽  
Vol 60 (1) ◽  
pp. 158-164 ◽  
Author(s):  
Erin A Bohula May ◽  
Marc P Bonaca ◽  
Petr Jarolim ◽  
Elliott M Antman ◽  
Eugene Braunwald ◽  
...  

Abstract BACKGROUND High-sensitivity assays for cardiac troponin enable more precise measurement of very low concentrations and improved diagnostic accuracy. However, the prognostic value of these measurements, particularly at low concentrations, is less well defined. METHODS We evaluated the prognostic performance of a new high-sensitivity cardiac troponin I (hs-cTnI) assay (Abbott ARCHITECT) compared with the commercial fourth generation cTnT assay in 4695 patients with non–ST-segment elevation acute coronary syndromes (NSTE-ACS) from the EARLY-ACS (Early Glycoprotein IIb/IIIa Inhibition in NSTE-ACS) and SEPIA-ACS1-TIMI 42 (Otamixaban for the Treatment of Patients with NSTE-ACS) trials. The primary endpoint was cardiovascular death or new myocardial infarction (MI) at 30 days. Baseline cardiac troponin was categorized at the 99th percentile reference limit (26 ng/L for hs-cTnI; 10 ng/L for cTnT) and at sex-specific 99th percentiles for hs-cTnI. RESULTS All patients at baseline had detectable hs-cTnI compared with 94.5% with detectable cTnT. With adjustment for all other elements of the TIMI risk score, patients with hs-cTnI ≥99th percentile had a 3.7-fold higher adjusted risk of cardiovascular death or MI at 30 days relative to patients with hs-cTnI &lt;99th percentile (9.7% vs 3.0%; odds ratio, 3.7; 95% CI, 2.3–5.7; P &lt; 0.001). Similarly, when stratified by categories of hs-cTnI, very low concentrations demonstrated a graded association with cardiovascular death or MI (P-trend &lt; 0.001). Use of sex-specific cutpoints did not improve prognostic performance. Patients with negative fourth generation cTnT (&lt;10 ng/L) but hs-cTnI ≥26 ng/L were at increased risk of cardiovascular death/MI compared to those with hs-cTnI &lt;26 ng/L (9.2% vs 2.9%, P = 0.002). CONCLUSIONS Application of this hs-cTnI assay identified a clinically relevant higher risk of recurrent events among patients with NSTE-ACS, even at very low troponin concentrations.


Author(s):  
Pascale Beyne ◽  
Erik Bouvier ◽  
Patrick Werner ◽  
Pierre Bourgoin ◽  
Damien Logeart ◽  
...  

AbstractThe aim of this study was to define the use of a new cardiac troponin I (cTnI) assay for emergency patients with chest pain and no specific electrocardiographic changes consistent with the presence of ischemia. Patients (n=106) admitted in Emergency/Cardiology Departments for chest pain and suspicion of acute coronary syndrome (ACS) were randomized into two diagnosis groups (ACS or non-ACS) by two independent cardiologists. cTnI measurements were performed at admission, and 6 hours and 12 hours later with a new generation assay (Access AccuTnI, Beckman Coulter). Using an upper reference limit of 0.04 μg/l, 27 patients had a cTnI elevation not related to the final diagnosis of ischemia; the positive predictive value (PPV) was 67% with specificity 48%. The decisional value was re-defined and set at 0.16 μg/l, a concentration corresponding to the 99th percentile of the non-ACS patient group. Precision (coefficient of variation) was 8% at this level, PPV 97% and specificity 98%. This new decisional value is now used in our institution and could be included in standard care guidelines to improve the management of patients presenting chest pain in emergency departments.


2017 ◽  
Vol 38 (suppl_1) ◽  
Author(s):  
V.J. Van Den Berg ◽  
V.A.W.M. Umans ◽  
K.M. Akkerhuis ◽  
R.M. Oemrawsingh ◽  
F.W. Asselbergs ◽  
...  

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