Estimation of Values below the Limit of Detection of a Contemporary Sensitive Troponin I Assay Improves Diagnosis of Acute Myocardial Infarction

Abstract BACKGROUND The limit of detection (LoD) is the minimal amount of a substance that can be consistently detected. In the diagnosis of acute myocardial infarction (AMI) many patients present with troponin concentrations below the LoD of contemporary sensitive cardiac troponin I (cs-cTnI) assays. These censored values below the LoD influence the diagnostic performance of these assays compared to highly sensitive cTnI (hs-cTnI) assays. Therefore we assessed the impact of a new approach for interpolation of the left-censored data of a cs-cTnI assay in the evaluation of patients with suspected AMI. METHODS Our posthoc analysis used a real world cohort of 1818 patients with suspected MI. Data on cs-cTnI was available in 1786 patients. As a comparator the hs-cTnI version of the assay was used. To reconstruct quantities below the LoD of the cs-cTnI assay, a gamma regression approach incorporating the GRACE (Global Registry of Acute Coronary Events) score variables was used. RESULTS Censoring of cs-cTnI data below the LoD yielded weaker diagnostic information [area under the curve (AUC), 0.781; 95% CI, 0.731–0.831] regarding AMI compared to the hs-cTnI assay (AUC, 0.949; CI, 0.936–0.961). Use of our model to estimate cs-cTnI values below the LoD showed an AUC improvement to 0.921 (CI, 0.902–0.940). The cs-cTnI LoD concentration had a negative predictive value (NPV) of 0.950. An estimated concentration that was to be undercut by 25% of patients presenting with suspected AMI was associated with an improvement of the NPV to 0.979. CONCLUSIONS Estimation of values below the LoD of a cs-cTnI assay with this new approach improves the diagnostic performance in evaluation of patients with suspected AMI.

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Circulating MiR-19b-3p, MiR-134-5p and MiR-186-5p are Promising Novel Biomarkers for Early Diagnosis of Acute Myocardial Infarction

Cellular Physiology and Biochemistry ◽

10.1159/000443053 ◽

2016 ◽

Vol 38 (3) ◽

pp. 1015-1029 ◽

Cited By ~ 68

Author(s):

Ke-Jing Wang ◽

Xin Zhao ◽

Yu-Zhou Liu ◽

Qiu-Tang Zeng ◽

Xiao-Bo Mao ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Troponin I ◽

Early Stage ◽

Diagnostic Efficiency ◽

Plasma Samples ◽

Circulating Mirnas ◽

Peak Expression ◽

And Gender ◽

The Impact

Background/Aims: Recent studies have shown that circulating microRNAs (miRNAs) are emerging as promising biomarkers for cardiovascular diseases. This study aimed to determine whether miR-19b-3p, miR-134-5p and miR-186-5p can be used as novel indicators for acute myocardial infarction (AMI). Methods: To investigate the kinetic expression of the three selected miRNAs, we enrolled 18 patients with AMI and 20 matched controls. Plasma samples were collected from each participant, and total RNA was extracted. Quantitative real-time PCR and ELISA assays were used to investigate the expression of circulating miRNAs and cardiac troponin I (cTnI), respectively. Plasma samples from another age- and gender-matched cohort were collected to investigate the impact of medications for AMI on the expression of the selected miRNAs. Results: Levels of plasma miR-19b-3p, miR-134-5p and miR-186-5p were significantly increased in early stage of AMI. Plasma miR-19b-3p and miR-134-5p levels reached peak expression immediately after admission (T0), whereas miR-186-5p achieved peak expression at 4 h after T0. All of these times were earlier than the peak for cTnI (8 h after T0). In addition, all three miRNAs were positively correlated with cTnI. Receiver Operating Characteristic (ROC) analysis indicated that each single miRNA showed considerable diagnostic efficiency for predicting AMI. Furthermore, combining all three miRNAs in a panel increased the efficiency of distinguishing between patients with AMI and controls. Moreover, we found that heparin and medications for AMI did not impact the expression of these circulating miRNAs. Conclusion: Circulating miR-19b-3p, miR-134-5p and miR-186-5p could be considered promising novel diagnostic biomarkers for the early phase of AMI.

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3304High sensitive cardiac troponin i at admission and 30 minutes later to rule-in or rule-out acute myocardial infarction - Preliminary results from the RACING-MI trial

European Heart Journal ◽

10.1093/eurheartj/ehz745.0068 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Cited By ~ 1

Author(s):

C Bang ◽

C Hansen ◽

K Glerup Lauridsen ◽

C Alcaraz Frederiksen ◽

M Schmidt ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Predictive Value ◽

Cardiac Troponin ◽

Diagnostic Performance ◽

Troponin I ◽

Final Diagnosis ◽

Cardiac Troponin I ◽

Emergency Department Patients ◽

Rule Out

Abstract Introduction Current ESC guidelines have introduced a 0h/1h algorithm for accelerated rule-in or rule-out of acute myocardial infarction (MI) when using assay specific high-sensitive cardiac troponin I (hs-cTnI). Several studies have investigated the diagnostic performance and safety of this approach using different hs-cTnI assays. However, little is known of the diagnostic performance of a 0h/30min algorithm. Purpose To evaluate the diagnostic accuracy of early rule-in or rule-out of MI after 30 minutes by applying assay specific hs-cTnI cut-off values from a recently validated 0h/1h algorithm. Methods We prospectively enrolled chest pain patients suggestive of MI admitted to the Emergency Department. Patients underwent serial hs-cTnI measurements at admission (0 hour) and after 3 hours according to clinical practice. In addition, hs-cTnI measurements were performed after 30 minutes. The assay specific cut-off values from the 0h/1h algorithm were applied to the 30 minute cohort (figure 1). Final diagnosis was adjudicated independently by two physicians. Results In total, 943 patients were included. MI was the final diagnosis in 67 (7.1%) patients. Overall, absolute hs-cTnI values after 30 minutes were significantly higher in the MI group than in the non-MI group (19.2 (Q1:Q3) 2.7–75.3) ng/L versus 0.1 (0.2–0.7) ng/L, p<0.001). When applying the assay-specific hs-cTnI cut-off valuesfor the 0h/1h algorithmto the 30 minute patient cohort, 52.4% of patients were classified as rule-out with a negative predictive value of 100% (95% CI: 99.2–100). In total, 8.5% were classified as rule-in with a positive predictive value of 83.8% (95% CI: 74.2–90.3). Sensitivity was 100% (95% CI: 94.6–100) and specificity was 97.4% (95% CI: 95.7–98.6). Overall, 39.1% were assigned to the observational zone with a 3.5% prevalence of MI. Conclusions The use of assay specific hs-cTnI measurement at admission (0h) and 30 min later can be used to safely rule-out MI. This indicates that it might be safe to develop a 0h/30min algorithm and hereby reduce time to diagnosis even further. NCT03634384. Acknowledgement/Funding Randers Regional Hospital, A.P Møller Foundation, Boserup Foundation, Korning Foundation, Højmosegård Grant, Siemens Healthcare (TNIH assays), etc.

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3720 The impact of the new definition of acute myocardial infarction on patients discharged with unstable angina pectoris. Six month outcomes: the Global Registry of Acute Coronary Events (GRACE)

European Heart Journal ◽

10.1016/s0195-668x(03)96272-5 ◽

2003 ◽

Vol 24 (5) ◽

pp. 723

Author(s):

M JELINEK

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Angina Pectoris ◽

Unstable Angina ◽

Unstable Angina Pectoris ◽

Coronary Events ◽

Definition Of ◽

The Impact ◽

Global Registry

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Diagnostic Performance of High Sensitivity Compared with Contemporary Cardiac Troponin I for the Diagnosis of Acute Myocardial Infarction

Clinical Chemistry ◽

10.1373/clinchem.2017.272930 ◽

2017 ◽

Vol 63 (10) ◽

pp. 1594-1604 ◽

Cited By ~ 23

Author(s):

Yader Sandoval ◽

Stephen W Smith ◽

Sarah E Thordsen ◽

Charles A Bruen ◽

Michelle D Carlson ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Cardiac Troponin ◽

Diagnostic Performance ◽

Troponin I ◽

High Sensitivity ◽

Cardiac Troponin I ◽

Serial Testing ◽

Safety Outcomes ◽

Acute Mi

Abstract BACKGROUND We examined the diagnostic performance of high-sensitivity cardiac troponin I (hs-cTnI) vs contemporary cTnI with use of the 99th percentile alone and with a normal electrocardiogram (ECG) to rule out acute myocardial infarction (MI) and serial changes (deltas) to rule in MI. METHODS We included consecutive patients presenting to a US emergency department with serial cTnI onclinical indication. Diagnostic performance for acute MI, including MI subtypes, and 30-day outcomes were examined. RESULTS Among 1631 patients, MI was diagnosed in 12.9% using the contemporary cTnI assay and in 10.4% using the hs-cTnI assay. For ruling out MI, contemporary cTnI ≤99th percentile at 0, 3, and 6 h and a normal ECG had a negative predictive value (NPV) of 99.5% (95% CI, 98.6–100) and a sensitivity of 99.1% (95% CI, 97.4–100) for diagnostic and safety outcomes. Serial hs-cTnI measurements ≤99th percentile at 0 and 3 h and a normal ECG had an NPV and sensitivity of 100% (95% CI, 100–100) for diagnostic and safety outcomes. For ruling in MI, contemporary cTnI measurements had specificities of 84.4% (95% CI, 82.5–86.3) at presentation and 78.7% (95% CI, 75.4–82.0) with serial testing at 0, 3, and 6 h, improving to 89.2% (95% CI, 87.1–91.3) by using serial cTnI changes (delta, 0 and 6 h) >150%. hs-cTnI had specificities of 86.9% (95% CI, 85.1–88.6) at presentation and 85.7% (95% CI, 83.5–87.9) with serial testing at 0 and 3 h, improving to 89.3% (95% CI, 87.3–91.2) using a delta hs-cTnI (0 and 3 h) >5 ng/L. CONCLUSIONS hs-cTnI and contemporary cTnI assays are excellent in ruling out MI following recommendations predicated on serial testing and the 99th percentile with a normal ECG. For ruling in MI, deltas improve the specificity. ClinicalTrials.gov Identifier: NCT02060760

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Clinical Evaluation of a New High-Sensitivity Cardiac Troponin I Assay for Diagnosis and Risk Assessment of Patients with Suspected Acute Myocardial Infarction

Cardiology ◽

10.1159/000512185 ◽

2021 ◽

pp. 1-7

Author(s):

Masayuki Shiozaki ◽

Kenji Inoue ◽

Satoru Suwa ◽

Chien-Chang Lee ◽

Shuo-Ju Chiang ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Diagnostic Accuracy ◽

Cardiac Troponin ◽

Troponin I ◽

Area Under The Curve ◽

High Sensitivity ◽

Major Adverse Cardiovascular Events ◽

Primary Analysis ◽

Rule Out

Introduction: Current assays based on the 0-hour/1-hour (0-/1-h) algorithm using high-sensitivity cardiac troponin (hs-cTn) are limited to only Abbott Architect hs-cTnI, Siemens Vista hs-cTnI, and Roche Elecsys hs-cTnT. Objective: This study aimed to evaluate this new hs-cTnI assay, LumipulsePresto hs Troponin I, for diagnosis of acute myocardial infarction (AMI) on admission and on 0-/1-h algorithm to stratify AMI patients precisely. Methods: This prospective cohort study included 442 patients with suspected non-ST-elevation myocardial infarction in three hospitals in Japan and Taiwan from June 2016 to January 2019. We enrolled patients presenting to the emergency department with symptoms suggestive of AMI and collected blood samples on admission and 1 hour later. Two independent cardiologists centrally adjudicated final diagnoses; all clinical information was reviewed twice: first, using serial hs-cTnT (Roche-Elecsys, primary analysis) and Lumipulse Presto Lumipulse Presto, second, using the Lumipulse Presto hs-cTnI measurements. At first, we compared diagnostic accuracy quantified using receiver operating characteristic (ROC) curves for AMI. Then, we evaluated major adverse cardiovascular events (cardiac death, AMI) in the rule-out group according to a 0-hour/1-hour algorithm at the 30-day follow-up. Results: Diagnostic accuracy at presentation by the ROC curve for AMI was very high and similar for the LumipulsePresto hs-cTnI and hs-cTnT,(area under the curve [AUC]: LumipulsePresto hs-cTnI, 0.89, 95% confidence interval [CI] 0.86–0.93; hs-cTnT, 0.89, 95% CI 0.85–0.93; p = 0.82). In early presenters, the LumipulsePresto hs-cTnI appeared to maintain the diagnostic performance of hs-cTn for patients with <3 h (AUC: LumipulsePresto hs-cTnI, 0.87, 95% CI 0.81–0.92; hs-cTnT, 0.86, 95% CI 0.80–0.92; p = 0.81). The algorithm using the LumipulsePresto hs-cTnI ruled out AMI in 200 patients with negative predictive value and sensitivity of 100% (95% CI 97.3%–100%) and 100% (95% CI 92.7%–100%), respectively, in the rule-out group. Conclusion: Diagnostic accuracy and clinical utility of the novel LumipulsePresto hs-cTnI assay are high and comparable with the established hs-cTn assays.

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