Biomarkers in acute coronary syndromes

Author(s):  
Jasper Boeddinghaus ◽  
Thomas Nestelberger ◽  
Raphael Twerenbold ◽  
Christian Mueller

Biomarkers, particularly high-sensitivity cardiac troponin T/I (hs-cTnT/I), play a major role in the early diagnosis and risk stratification of patients presenting with symptoms suggestive of an acute coronary syndrome such as acute chest pain. As heart specific markers of cardiomyocyte injury, hs-cTnT/I complement clinical assessment and the 12-lead electrocardiogram in the diagnosis of myocardial infarction, the risk stratification for life-threatening arrhythmias and death, and the triage towards early revascularization. Hs-cTnT/I allow the reliable measurement of cTnT/I concentrations around the 99th-percentile and in the normal range and increased the diagnostic accuracy for myocardial infarction at presentation. Absolute short-term changes in hs-cTnT/I within 1h or 2h further increase the diagnostic accuracy for myocardial infarction. The ESC hs-cTnT/I 0/1h-algorithms are assay-specific early triage algorithms optimized for the early rule-out and/or rule-in of myocardial infarction. They triage patients towards rule-out (about 60%), observe (about 25%), and rule-in (about 15%). Triage towards rule-out provides very high sensitivity (99%) and negative predictive value (>99%) for the safe rule-out of myocardial infarction, while triage towards rule-in provides high specificity (about 96%) and positive predictive value (about 75%) for myocardial infarction. Other biomarkers quantifying cardiomyocyte injury (e.g. CK-MB, CK, LDH, myosin-binding protein C) or other pathophysiological processes involved in acute coronary syndromes (e.g. copeptin, BNP, NT-proBNP) provide no or only very little incremental diagnostic value for myocardial infarction on top of the ESC hs-cTnT/I 0/1h-algorithms. However, the later provide incremental prognostic value for death and heart failure. Therefore, the use of BNP or NT-proBNP, as quantitative markers of hemodynamic stress and heart failure, should be considered.

2019 ◽  
Vol 37 (1) ◽  
pp. 8-13 ◽  
Author(s):  
Richard Body ◽  
Niall Morris ◽  
Charles Reynard ◽  
Paul O Collinson

ObjectivesTo directly compare the diagnostic accuracy of four decision aids (Troponin-only Manchester Acute Coronary Syndromes (T-MACS), History, ECG, Age, Risk factors and Troponin (HEART), Thrombolysis in Myocardial Infarction (TIMI) and Emergency Department Assessment of Chest Pain (EDACS)) used to expedite the early diagnosis of acute coronary syndromes (ACS) in the ED.MethodsWe prospectively included patients who presented to 14 EDs in England (February 2015 to June 2017) with suspected ACS within 12 hours of symptom onset. Data to enable evaluation of the T-MACS, HEART, TIMI and EDACS decision aids (without recalibration) were prospectively collected, blinded to patient outcome. We tested admission blood samples for high-sensitivity cardiac troponin I (hs-cTnI; Siemens ADVIA Centaur). Patients also underwent serial cardiac troponin testing over 3–12 hours. The target condition was an adjudicated diagnosis of acute myocardial infarction (AMI). We also evaluated the incidence of major adverse cardiac events (including death, AMI or coronary revascularisation) at 30 days. Diagnostic accuracy of each decision aid and hs-cTnI alone (using the limit of quantification cut-off, 3 ng/L) was evaluated by calculating sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV).ResultsOf 999 included patients, 132 (13.2%) had AMI. C-statistics were 0.96 for T-MACS, 0.78 for HEART and 0.69 for TIMI. The sensitivities of T-MACS, HEART, TIMI, EDACS and hs-cTnI <3 ng/L for AMI were 99.2% (95% CI 95.7% to 100.0%), 91.8% (85.0% to 96.2%), 97.5% (92.9% to 99.5%), 96.2% (92.2% to 99.4%) and 99.2% (95.9% to 100.0%), respectively. The respective strategies would have ruled out 46.5%, 34.9%, 19.4%, 48.3% and 28.8% patients. PPVs for the decision aids that identify ‘high-risk’ patients were 80.4% (T-MACS), 51.9% (TIMI) and 37.2% (HEART).ConclusionsIn this study, T-MACS could rule out AMI in 46.5% patients with 99.2% sensitivity. EDACS could rule out AMI in 48.3% patients with lower sensitivity, although the difference was not statistically significant. The HEART and TIMI scores had lower diagnostic accuracy.


ESC CardioMed ◽  
2018 ◽  
pp. 1232-1241
Author(s):  
Christian Mueller

Detailed clinical assessment including vital signs; physical examination; a thorough patient history including chest pain characteristics, the 12-lead electrocardiogram, high-sensitivity cardiac troponin, and cardiac imaging are the four pillars in the early diagnosis and risk stratification of patients presenting with a suspected myocardial infarction. High-sensitivity cardiac troponin assays allow the precise quantification of cardiomyocyte injury around the 99th percentile and thereby substantially increase the accuracy of myocardial infarction detection from blood obtained at presentation to the emergency department. Higher accuracy at emergency department presentation enabled the development and extensive validation of early high-sensitivity cardiac troponin-based diagnostic algorithms, which substantially reduced the time required for the safe rule-out or rule-in of myocardial infarction. More rapid rule-out and rule-in of myocardial infarction provides substantial medical value to patients, physicians, and institutions.


ESC CardioMed ◽  
2018 ◽  
pp. 1232-1241
Author(s):  
Christian Mueller

Detailed clinical assessment including vital signs; physical examination; a thorough patient history including chest pain characteristics, the electrocardiogram, and high-sensitivity cardiac troponin; and cardiac imaging are the four pillars in the early diagnosis and risk stratification of patients presenting with a suspected myocardial infarction. High-sensitivity cardiac troponin assays for the first time allowed the precise quantification of cardiomyocyte injury around the 99th percentile and thereby substantially increased the accuracy of myocardial infarction detection from blood obtained at presentation to the emergency department. Higher accuracy at emergency department presentation enabled the development and extensive validation of early high-sensitivity cardiac troponin-based diagnostic algorithms, which substantially reduced the time required for the safe rule-out or rule-in of myocardial infarction. More rapid rule-out and rule-in of myocardial infarction provides substantial medical value to patients, physicians, and institutions.


BMJ Open ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. e032834 ◽  
Author(s):  
Abdulrhman Alghamdi ◽  
Eloïse Cook ◽  
Edward Carlton ◽  
Aloysius Siriwardena ◽  
Mark Hann ◽  
...  

IntroductionWithin the UK, chest pain is one of the most common reasons for emergency (999) ambulance calls and the most common reason for emergency hospital admission. Diagnosing acute coronary syndromes (ACS) in a patient with chest pain in the prehospital setting by a paramedic is challenging. The Troponin-only Manchester Acute Coronary Syndromes (T-MACS) decision rule is a validated tool used in the emergency department (ED) to stratify patients with suspected ACS following a single blood test.We are seeking to evaluate the diagnostic accuracy of the T-MACS decision aid algorithm to ‘rule out’ ACS when used in the prehospital environment with point-of-care troponin assays. If successful, this could allow paramedics to immediately rule out ACS for patients in the ‘very low risk’ group and avoid the need for transport to the ED, while also risk stratifying other patients using a single blood sample taken in the prehospital setting.Methods and analysisWe will recruit patients who call emergency (999) ambulance services where the responding paramedic suspects cardiac chest pain. The data required to apply T-MACS will be prospectively recorded by paramedics who are responding to each patient. Paramedics will be required to draw a venous blood sample at the time of arrival to the patient. Blood samples will later be tested in batches for cardiac troponin, using commercially available troponin assays. The primary outcome will be a diagnosis of acute myocardial infarction, established at the time of initial hospital admission. The secondary outcomes will include any major adverse cardiac events within 30 days of enrolment.Ethics and disseminationThe study obtained approval from the National Research Ethics Service (reference: 18/ES/0101) and the Health Research Authority. We will publish our findings in a high impact general medical journal.Trial registration numberRegistration number: ClinicalTrials.gov, study ID: NCT03561051


2017 ◽  
Vol 7 (6) ◽  
pp. 570-576 ◽  
Author(s):  
Christian Mueller ◽  
Martin Möckel ◽  
Evangelos Giannitsis ◽  
Kurt Huber ◽  
Johannes Mair ◽  
...  

Copeptin is currently understood as a quantitative marker of endogenous stress. It rises rapidly in multiple acute disorders including acute myocardial infarction. As a single variable, it has only modest diagnostic accuracy for acute myocardial infarction. However, the use of copeptin within a dual-marker strategy together with conventional cardiac troponin increases the diagnostic accuracy and particularly the negative predictive value of cardiac troponin alone for acute myocardial infarction. The rapid rule-out of acute myocardial infarction is the only application in acute cardiac care mature enough to merit consideration for routine clinical care. However, the dual-marker approach seems to provide only very small incremental value when used in combination with sensitive or high-sensitivity cardiac troponin assays. This review aims to update and educate regarding the potential and the procedural details, as well as the caveats and challenges of using copeptin in clinical practice.


2015 ◽  
Vol 65 (10) ◽  
pp. A773
Author(s):  
Giulia Magnani ◽  
Michelle O’Donoghue ◽  
Eugene Braunwald ◽  
Dylan Steen ◽  
Petr Jarolim ◽  
...  

ESC CardioMed ◽  
2018 ◽  
pp. 1255-1276
Author(s):  
Borja Ibanez ◽  
Sigrun Halvorsen

Over the last 50 years, the treatment of acute ST-segment elevation myocardial infarction (STEMI) has been considerably improved. The widespread implementation of reperfusion (initially pharmacological and later mechanical) resulted in a magnificent reduction in the rates of in-hospital mortality from about 25% in the 1970s to 5% in the late 2010s. Mortality in real life, however, is higher than these figures shown in clinical trials. There is compelling evidence showing the association between duration of ischaemia and mortality. This is the basis for the timely reperfusion in STEMI. All actions should be made to reduce all components of the ischaemic time. Despite these advances, STEMI survivors are still at high risk for developing repetitive events, including reinfarctions, heart failure, and sudden death. Evolving therapies beyond timely reperfusion are contributing to further reduce the morbidity associated with STEMI.


Author(s):  
Evangelos Giannitsis ◽  
Hugo A Katus

Biomarker testing in the evaluation of a patient with acute chest pain is best established for cardiac troponins that allow the diagnosis of myocardial infarction, risk estimation of short- and long-term risk of death and myocardial infarction, and guidance of pharmacological therapy, as well as the need and timing of invasive strategy. Newer, more sensitive troponin assays have become commercially available and have the capability to detect myocardial infarction earlier and more sensitively than standard assays, but they are hampered by a lack of clinical specificity, i.e. the ability to discriminate myocardial ischaemia from myocardial necrosis not related to ischaemia such as myocarditis, pulmonary embolism, or decompensated heart failure. Strategies to improve clinical specificity (including strict adherence to the universal myocardial infarction definition and the need for serial troponin measurements to detect an acute rise and/or fall of cardiac troponin) will improve the interpretation of the increasing number of positive results. Other biomarkers of inflammation, activated coagulation/fibrinolysis, and increased ventricular stress mirror different aspects of the underlying disease activity and may help to improve our understanding of the pathophysiological mechanisms of acute coronary syndromes. Among the flood of new biomarkers, there are several novel promising biomarkers, such as copeptin that allows an earlier rule-out of myocardial infarction in combination with cardiac troponin, whereas MR-proANP and MR-proADM appear to allow a refinement of cardiovascular risk. GDF-15 might help to identify candidates for an early invasive vs conservative strategy. A multi-marker approach to biomarkers becomes more and more attractive, as increasing evidence suggests that a combination of several biomarkers may help to predict individual risk and treatment benefits, particularly among normal-troponin subjects. Future goals include the acceleration of rule-in and rule-out of patients with suspected acute coronary syndrome, in order to shorten lengths of stay in the emergency department, and to optimize patient management and the use of health care resources. New algorithms using high-sensitivity cardiac troponin assays at low cut-offs alone, or in combination with additional biomarkers, allow to establish accelerated rule-out algorithms within 1 or 2 hours.


Author(s):  
Eric Durand ◽  
Aurès Chaib ◽  
Etienne Puymirat ◽  
Nicolas Danchin

Patients presenting at the emergency department with acute chest pain and suspected to represent an acute coronary syndrome were classically admitted as routine to the cardiology department, resulting in expensive and time-consuming evaluations. However, 2-5% of patients with acute coronary syndromes were discharged home inappropriately, resulting in increased mortality. To address the inability to exclude the diagnosis of acute coronary syndrome, chest pain units were developed, particularly in the United States. These provide an environment where serial electrocardiograms, cardiac biomarkers, and provocative testing can be performed to confirm or rule out an acute coronary syndrome. Eligible candidates include the majority of patients with non-diagnostic electrocardiograms. The results have been impressive; chest pain units have markedly reduced adverse events, while simultaneously increasing the rate of safe discharge by 36%. Despite evidence to suggest that care in chest pain units is more effective for such patients, the percentage of emergency or cardiology departments setting up chest pain units remains low in Europe.


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