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

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 2 /L 2 ) 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.

Download Full-text

Two-Hour Algorithm for Rapid Triage of Suspected Acute Myocardial Infarction Using a High-Sensitivity Cardiac Troponin I Assay

Clinical Chemistry ◽

10.1373/clinchem.2019.305193 ◽

2019 ◽

Vol 65 (11) ◽

pp. 1437-1447 ◽

Cited By ~ 9

Author(s):

Thomas Nestelberger ◽

Jasper Boeddinghaus ◽

Jaimi Greenslade ◽

William A Parsonage ◽

Martin Than ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Predictive Value ◽

Cardiac Troponin ◽

Troponin I ◽

Validation Cohort ◽

High Sensitivity ◽

Final Diagnosis ◽

Derivation Cohort ◽

Rule Out

Abstract BACKGROUND We aimed to derive and externally validate a 0/2-h algorithm using the high-sensitivity cardiac troponin I (hs-cTnI)-Access assay. METHODS We enrolled patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction (AMI) in 2 prospective diagnostic studies using central adjudication. Two independent cardiologists adjudicated the final diagnosis, including all available medical information including cardiac imaging. hs-cTnI-Access concentrations were measured at presentation and after 2 h in a blinded fashion. RESULTS AMI was the adjudicated final diagnosis in 164 of 1131 (14.5%) patients in the derivation cohort. Rule-out by the hs-cTnI-Access 0/2-h algorithm was defined as 0-h hs-cTnI-Access concentration <4 ng/L in patients with an onset of chest pain >3 h (direct rule-out) or a 0-h hs-cTnI-Access concentration <5 ng/L and an absolute change within 2 h <5 ng/L in all other patients. Derived thresholds for rule-in were a 0-h hs-cTnI-Access concentration ≥50 ng/L (direct rule-in) or an absolute change within 2 h ≥20 ng/L. In the derivation cohort, these cutoffs ruled out 55% of patients with a negative predictive value (NPV) of 99.8% (95% CI, 99.3–100) and sensitivity of 99.4% (95% CI, 96.5–99.9), and ruled in 30% of patients with a positive predictive value (PPV) of 73% (95% CI, 66.1–79). In the validation cohort, AMI was the adjudicated final diagnosis in 88 of 1280 (6.9%) patients. These cutoffs ruled out 77.9% of patients with an NPV of 99.8% (95% CI, 99.3–100) and sensitivity of 97.7% (95% CI, 92.0–99.7), and ruled in 5.8% of patients with a PPV of 77% (95% CI, 65.8–86) in the validation cohort. CONCLUSIONS Safety and efficacy of the l hs-cTnI-Access 0/2-h algorithm for triage toward rule-out or rule-in of AMI are very high. TRIAL REGISTRATION APACE, NCT00470587; ADAPT, ACTRN1261100106994; IMPACT, ACTRN12611000206921.

Download Full-text

Two-Hour Algorithm for Triage toward Rule-Out and Rule-In of Acute Myocardial Infarction by Use of High-Sensitivity Cardiac Troponin I

Clinical Chemistry ◽

10.1373/clinchem.2015.249508 ◽

2016 ◽

Vol 62 (3) ◽

pp. 494-504 ◽

Cited By ~ 63

Author(s):

Jasper Boeddinghaus ◽

Tobias Reichlin ◽

Louise Cullen ◽

Jaimi H Greenslade ◽

William A Parsonage ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Cardiac Troponin ◽

Troponin I ◽

Validation Cohort ◽

External Validation ◽

High Sensitivity ◽

Final Diagnosis ◽

Derivation Cohort ◽

Rule Out

Abstract BACKGROUND The early triage of patients toward rule-out and rule-in of acute myocardial infarction (AMI) is challenging. Therefore, we aimed to develop a 2-h algorithm that uses high-sensitivity cardiac troponin I (hs-cTnI). METHODS We prospectively enrolled 1435 (derivation cohort) and 1194 (external validation cohort) patients presenting with suspected AMI to the emergency department. The final diagnosis was adjudicated by 2 independent cardiologists. hs-cTnI was measured at presentation and after 2 h in a blinded fashion. We derived and validated a diagnostic algorithm incorporating hs-cTnI values at presentation and absolute changes within the first 2 h. RESULTS AMI was the final diagnosis in 17% of patients in the derivation and 13% in the validation cohort. The 2-h algorithm developed in the derivation cohort classified 56% of patients as rule-out, 17% as rule-in, and 27% as observation. Resulting diagnostic sensitivity and negative predictive value (NPV) were 99.2% and 99.8% for rule-out; specificity and positive predictive value (PPV) were 95.2% and 75.8% for rule-in. Applying the 2-h algorithm in the external validation cohort, 60% of patients were classified as rule-out, 13% as rule-in, and 27% as observation. Diagnostic sensitivity and NPV were 98.7% and 99.7% for rule-out; specificity and PPV were 97.4% and 82.2% for rule-in. Thirty-day survival was 100% for rule-out patients in both cohorts. CONCLUSIONS A simple algorithm incorporating hs-cTnI baseline values and absolute 2-h changes allowed a triage toward safe rule-out or accurate rule-in of AMI in the majority of patients.

Download Full-text

Faculty Opinions recommendation of One-hour rule-in and rule-out of acute myocardial infarction using high-sensitivity cardiac troponin I.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725420089.793507697 ◽

2015 ◽

Author(s):

Patrick Ray

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Cardiac Troponin ◽

Troponin I ◽

High Sensitivity ◽

Cardiac Troponin I ◽

Rule Out

Download Full-text

Acceptable Analytical Variation May Exceed High-Sensitivity Cardiac Troponin I Cutoffs in Early Rule-Out and Rule-In Acute Myocardial Infarction Algorithms

Clinical Chemistry ◽

10.1373/clinchem.2016.255448 ◽

2016 ◽

Vol 62 (6) ◽

pp. 887-889 ◽

Cited By ~ 36

Author(s):

Peter A Kavsak ◽

Andrew C Don-Wauchope ◽

Stephen A Hill ◽

Andrew Worster

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Cardiac Troponin ◽

Troponin I ◽

High Sensitivity ◽

Cardiac Troponin I ◽

Analytical Variation ◽

Rule Out

Download Full-text

Direct Comparison of 4 Very Early Rule-Out Strategies for Acute Myocardial Infarction Using High-Sensitivity Cardiac Troponin I

Circulation ◽

10.1161/circulationaha.116.025661 ◽

2017 ◽

Vol 135 (17) ◽

pp. 1597-1611 ◽

Cited By ~ 80

Author(s):

Jasper Boeddinghaus ◽

Thomas Nestelberger ◽

Raphael Twerenbold ◽

Karin Wildi ◽

Patrick Badertscher ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Cardiac Troponin ◽

Troponin I ◽

High Sensitivity ◽

Cardiac Troponin I ◽

Rule Out

Download Full-text

One-hour algorithm for early rule-out and rule-in of acute myocardial infarction using sensitive cardiac troponin i

European Heart Journal ◽

10.1093/eurheartj/eht308.p1300 ◽

2013 ◽

Vol 34 (suppl 1) ◽

pp. P1300-P1300

Author(s):

M. Rubini Gimenez ◽

R. Twerenbold ◽

T. Reichlin ◽

B. Meller ◽

B. Moehring ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Cardiac Troponin ◽

Troponin I ◽

Cardiac Troponin I ◽

Rule Out

Download Full-text

44 Rapid Rule-Out of Type 1 Acute Myocardial Infarction Using a Contemporary Cardiac Troponin I Assay with Initial Undetectable Concentrations or Serial Concentrations Below the 99th Percentile

Annals of Emergency Medicine ◽

10.1016/j.annemergmed.2016.08.054 ◽

2016 ◽

Vol 68 (4) ◽

pp. S19

Author(s):

S.W. Smith ◽

Y. Sandoval ◽

J. Cao ◽

S.A. Love ◽

K. Schulz ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Cardiac Troponin ◽

Troponin I ◽

Cardiac Troponin I ◽

Rule Out

Download Full-text

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.

Download Full-text