Usefulness of Early Rule-In and Rule-Out Biomarker Protocols to Estimate Ischemia-Induced Myocardial Injury in Early Chest Pain Presenters

doi:10.1016/j.amjcard.2015.03.012

The American Journal of Cardiology

Volume 115, Issue 12, 15 June 2015, Pages 1667-1671

https://doi.org/10.1016/j.amjcard.2015.03.012 Get rights and content

Protocols to minimize the time between 2 measurements of troponin or a combination with copeptin have been developed to rapidly rule-in or rule-out myocardial injury (MI) in patients with chest pain. These fast track protocols to rule-in and rule-out MI are not sufficiently validated for early chest pain presenters. The “early presenter” model was tested in 107 stable patients after a short period of myocardial ischemia, induced by stenting of a significant coronary artery stenosis. High-sensitivity troponin T (hsTnT), high-sensitivity troponin I (hsTnI), and copeptin were measured at the start and 90, 180, and 360 minutes after stent implantation. MI was defined as a troponin level more than the upper limit of normal (ULN) and an absolute increase of >50% ULN on the 360-minute sample. A single combined measurement of troponin and copeptin 90 minutes after the onset of ischemia has a low diagnostic value. This increases when serial measurements with 90-minute intervals are included. For ruling in MI, the highest positive predictive value (with a 95% confidence interval [CI]) can be obtained when focusing only on the increase in troponin level, with a positive predictive value of 86% (70, 93) and 80% (67, 90) for hsTnT and hsTnI, respectively. For ruling out MI, a combined absence of any troponin more than the ULN and any significant increase in troponin level perform best with a negative predictive value of 75% (55, 89) and 75% (55, 89) for hsTnT and hsTnI, respectively. In conclusion, in early presenters, rapid biomarker protocols underestimate MI. A standard biomarker assessment after 3 hours is required to adequately rule-in or rule-out myonecrosis.

Section snippets

Methods

The “early presenter” model was tested in 107 consecutive stable patients in whom a short period of myocardial ischemia was induced during a percutaneous coronary intervention (PCI) of a significant coronary artery stenosis. The time between the onset of pain/ischemia and the first biomarker evaluation was fixed at 90 minutes, and a subsequent biomarker measurement was taken 90 minutes after this first biomarker assessment. Exclusion criteria included a recent myocardial infarction (<1 week), a

Results

A total of 107 patients with a planned PCI were enrolled. Table 1 describes the patient characteristics and procedure-related details. Most patients had a TIMI 3 flow before the percutaneous procedure; there was a TIMI 2 flow in 1 patient and a TIMI 1 flow in 8 patients. The PCI was complicated by 5 dissections of the coronary artery and 1 perforation, which were adequately covered by stents. In 1 patient, there was temporarily no reflow phenomenon during the procedure, and 1 patient showed

Discussion

The present study evaluated the usefulness of early rule-in and rule-out biomarker protocols to estimate ischemia-induced MI in an early presenter model and confirmed our hypothesis that these protocols would underestimate myonecrosis in these patients.

Myonecrosis after PCI was present in 56% to 62% of the patients of our population. The release of cardiac enzyme post-PCI is because of prolonged ischemia after epicardial coronary complications (e.g., side-branch occlusion of coronary

Acknowledgment

The authors wish to thank M.I. Schoorl from the Laboratorium voor KCHI, Medisch Centrum Alkmaar, The Netherlands, for the measurement of copeptin. They are also indebted to Abbott Diagnostics, B.R.A.H.M.S./Thermofisher Scientific, and Roche Diagnostics, for providing the reagents for the measurement of hsTnI, copeptin, and hsTnT, respectively. Finally, we thank Mrs. Domine Torfs for the measurements of biomarkers done in our laboratory.

References (15)

L. Cullen et al.
Validation of high-sensitivity troponin I in a 2-hour diagnostic strategy to assess 30-day outcomes in emergency department patients with possible acute coronary syndrome
J Am Coll Cardiol
(2013)
A. Maisel et al.
Copeptin helps in the early detection of patients with acute myocardial infarction: primary results of the CHOPIN trial (Copeptin Helps in the Early Detection of Patients with Acute Myocardial Infarction)
J Am Coll Cardiol
(2013)
M. Than et al.
2-Hour accelerated diagnostic protocol to assess patients with chest pain symptoms using contemporary troponins as the only biomarker: the ADAPT trial
J Am Coll Cardiol
(2012)
C.W. Hamm et al.
ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: the Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC)
Eur Heart J
(2011)
T. Reichlin et al.
One-hour rule-out and rule-in of acute myocardial infarction using high-sensitivity cardiac troponin T
Arch Intern Med
(2012)
M. Rubini Gimenez et al.
Direct comparison of high-sensitivity-cardiac troponin I vs. T for the early diagnosis of acute myocardial infarction
Eur Heart J
(2014)
K. Thygesen et al.
How to use high-sensitivity cardiac troponins in acute cardiac care
Eur Heart J
(2012)

There are more references available in the full text version of this article.

Cited by (7)

Implementing the European Society of Cardiology 0-h/1-h algorithm in patients presenting very early after chest pain
2020, International Journal of Cardiology
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There are few reports about the kinetics of hs-cTnT in patients with NSTEMI. Vorlat et al. measured hs-cTnT levels in patients with stable coronary artery stenosis after implantation of a stent immediately and 90 min later and showed that the increasing troponin level at 90 min could aid the clinician make a diagnosis of AMI with a PPV of 86% [21], indicating that hs-cTnT concentrations in patients with AMI dramatically increase over time. Therefore, Reichlin et al. emphasized the importance of absolute rather than relative changes in troponin, as well as the use of thresholds below the 99th percentile for the rule-out group [14], and a delta value (<3 ng/L or >52 ng/L) is a number as crucial as the 99th percentile to rule out AMI.
The European Society of Cardiology (ESC) recommends a 0-h/1-h (0/1-h) algorithm to classify patients with suspected non-ST-segment elevation myocardial infarction (NSTEMI). However, reliable evidence about patients who present early after the onset of symptoms is limited, likely because high-sensitivity cardiac troponin (hs-cTn) values cannot increase sufficiently within that time. This study aimed to evaluate the outcomes in real-world situations that utilized the 0/1-h algorithm.
In a prospective, international, multicenter cohort study that enrolled 1638 patients presenting with acute chest pain to the emergency department, we assessed the performance of the 0/1-h algorithm using hs-cTnT and the associated 30-day rates of major adverse cardiac events: death and acute myocardial infarction (AMI).
Among 1074 patients, the prevalence of AMI was 16.0%. An approximately 60.1% (n = 645) of patients visited the hospital within 3 h after onset of chest pain (less than 1 h; 18.2% [n = 196], less than 2 h; 27.5% [n = 295], and less than 3 h; 14.3% [n = 154]). Moreover, the prevalence rates of AMI were similar at all times (1 h, 16.8%; 1–2 h, 20.7%; 2–3 h, 18.2%; p = .5). According to the ESC 0/1-h algorithm, the distribution patterns of rule-out, observe, and rule-in groups were similar; however, none of the patients was diagnosed with AMI or cardiac death in the rule-out group.
This study revealed the applicability of the 0/1-h algorithm for the management of early presenters.
Diagnostic Accuracy of High-Sensitivity Cardiac Troponin T at Presentation Combined With History and ECG for Ruling Out Major Adverse Cardiac Events
2016, Annals of Emergency Medicine
Citation Excerpt :
Even though the combined strategy using hs-cTnT level less than 5 ng/L performed well also in these patients, acute myocardial infarction patients who had an hs-cTnT measurement within 2 hours from symptom onset were few. Because of the possible risk of false-negative results for these patients,30 we recommend serial hs-cTnT testing for very early presenters. Most patients identified for rule-out were younger than 65 years.
We evaluate the diagnostic accuracy of a high-sensitivity cardiac troponin T (hs-cTnT) level less than 5 ng/L or less than or equal to 14 ng/L at emergency department (ED) presentation, combined with the emergency physician’s assessment of history and ECG, for ruling out major adverse cardiac events within 30 days.
This prospective observational study enrolled consecutive ED chest pain patients. Emergency physicians’ assessments of patient history and ECG were collected. The primary outcome was 30-day major adverse cardiac events, defined as acute myocardial infarction, unstable angina, cardiogenic shock, ventricular arrhythmia, atrioventricular block, cardiac arrest, or death of cardiac or unknown cause.
A total of 1,138 patients were included in the final analysis. The combination of hs-cTnT less than 5 ng/L, a nonischemic ECG result, and a nonhigh risk history was present for 29.2% of all patients and had a sensitivity of 99.2% (95% confidence interval [CI] 95.6% to 100%), negative predictive value (NPV) of 99.7% (95% CI 98.3% to 100%), and a negative likelihood ratio of 0.02 (95% CI 0 to 0.17) for 30-day major adverse cardiac events. The same combination with hs-cTnT less than or equal to 14 ng/L was present in 66.7% of the patients and had a sensitivity of 92% (95% CI 85.8% to 96.1%), NPV of 98.7% (95% CI 97.6% to 99.4%), and negative likelihood ratio of 0.11 (95% CI 0.06 to 0.20).
A single hs-cTnT result of less than 5 ng/L at ED presentation when combined with a nonischemic ECG result and a nonhigh risk history identified 29% of chest pain patients at a very low risk of 30-day major adverse cardiac events. A similar strategy with hs-cTnT less than or equal to 14 ng/L was associated with a higher miss rate.
TRAPID or Trapped?
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Biomarkers and Donor Selection in Heart Transplantation
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For the remaining 41 patients, measurement of high-sensitivity troponin T was performed using a modular immunoassay instrument (Cobas 6000, Roche Diagnostics, Inc, Vilvoorde, Belgium) with Roche reagents. To achieve a uniform troponin assay, a conversion factor was applied to calculate high-sensitivity troponin T from troponin I, based on previous work [9]. ST2 was determined with the Aspect-PLUS ST2 Rapid Test (Critical Diagnostics Inc, Dublin, Ireland).
Previously, we showed that B-type natriuretic peptide (BNP) measured in the donor was related to cardiac performance after cardiac transplantation. The present study assesses the value of 3 biomarkers in the selection of donor hearts in a larger cohort.
Blood samples were prospectively obtained in 105 brain-dead patients scheduled for heart donation. BNP, soluble suppressor of tumorigenicity 2 (ST2), and troponin of heart donors were correlated with hemodynamic parameters early after transplantation as well as with the mortality of the recipients.
A significant inverse relationship was found between donor BNP measured at the time of donation and recipient cardiac index and cardiac output at day 13 post-transplantation (r = −0.31, P = .005, and r = −0.34, P = .0016, respectively). Logistic regression analysis—including BNP, ST2, and troponin—showed that donor BNP was a predictor of a poor cardiac index (< 2.2 L/min/m²) in the recipient (P = .04). A donor BNP > 132 pg/mL has a sensitivity of 56% (95% confidence interval 21–86) and a specificity of 86% (95% confidence interval 77–93) to predict poor cardiac performance in the recipient. When the donor BNP is ≤ 132 pg/mL, the risk of a poor cardiac function in the recipient is very low (negative predictive value 94%). Mortality at 30 days was also correlated to donor BNP (r = 0.29, P = .0029). Long-term survival of the recipient was not correlated to the biomarkers measured in the donor.
Donor BNP, but not donor ST2 or high-sensitivity troponin, provides information on the donor heart and early post-transplant performance, including 1-month mortality.
Incremental value of copeptin in suspected acute myocardial infarction very early after symptom onset
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Coronary Artery DiseaseUsefulness of Early Rule-In and Rule-Out Biomarker Protocols to Estimate Ischemia-Induced Myocardial Injury in Early Chest Pain Presenters

Section snippets

Methods

Results

Discussion

Acknowledgment

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Eur Heart J

One-hour rule-out and rule-in of acute myocardial infarction using high-sensitivity cardiac troponin T

Arch Intern Med

Direct comparison of high-sensitivity-cardiac troponin I vs. T for the early diagnosis of acute myocardial infarction

Eur Heart J

How to use high-sensitivity cardiac troponins in acute cardiac care

Eur Heart J

Coronary Artery Disease
Usefulness of Early Rule-In and Rule-Out Biomarker Protocols to Estimate Ischemia-Induced Myocardial Injury in Early Chest Pain Presenters