SEQC Spanish Society of Laboratory Medicine

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• The concentration of cardiac troponin increases early in blood when there is myocardial damage from any cause

• Increases in cardiac troponin, together with clinical signs and symptoms, make it possible to diagnose acute myocardial infarction with certainty and precocity

• The absence of an increase in cardiac troponin rules out the existence of significant myocardial damage; this allows shorter observation times to rule out acute myocardial infarction in patients who do not have it

The possibility of measuring cardiac troponin (Tnc) has been for many years a major step forward in the diagnosis of acute myocardial infarction (AMI) and other cardiac and extra-cardiac pathologies affecting the heart. Currently, in clinical practice, there are coexisting methods that allow for the measurement of normal, low, or very low Tnc concentrations with the recommended analytical quality. Measuring very low concentrations of Tnc (high sensitivity Tnc, Tnc-hs) allows for the identification of myocardial damage that is not detectable with methods that do not measure such low concentrations (Tnc-contemporaneous) with the recommended quality. Given this varying ability of analytical methods to recognize myocardial damage, the use of Tnc in cardiac diagnosis can generate confusion in certain circumstances. For this reason, the Spanish Society of Laboratory Medicine (SEQC^ML), Urgent and Emergency Medicine (SEMES), and Cardiology (SEC) have developed a consensus document on the use of Tnc in the differential diagnosis of AMI, whatever the measurement method used. This document has been published in the journal Emergencias, an organ of the SEMES, and can be accessed through the SEMES website and in the member-restricted area of the SEQC^ML website.

"Tnc is very commonly used in emergency services because it is very simple to determine and the information it provides is very valuable. It allows for rapid differentiation between a potentially serious patient with high Tnc and a potentially less severe patient with a non-elevated Tnc; this differentiation is an excellent help for Emergency Department doctors", explains Dr. Juan Sanchís, head of the Interventional Cardiology Unit of the Hospital Clínic Universitari de Valencia. Dr. Sanchís points out that a high concentration of Tnc may be indicative of diseases other than AMI, so it is necessary to interpret this biomarker well. "One of the drawbacks of the measurement of Tnc, especially if it is measured with high sensitivity methods, is to cause over-diagnosis of AMI, because it tends to prioritize this diagnosis over other alternatives that a patient with elevated Tnc may present", adds the specialist.

"Despite all the valuable contributions of Tnc, some doubts have been generated in the interpretation of its results, which this consensus document aims to clarify," says Dr. Sanchís. These questions are summarized in three questions to which the document gives an answer: "How are the various immunoassay methods for measuring Tnc different?"; "Does a normal troponin result rule out an AMI and can it guarantee a rapid and safe discharge of the patient from the emergency department? "; and finally, "When does an elevated Tnc indicate an AMI and when does it signal other causes of myocardial damage?".

Dr. Aitor Alquézar, associate of the Emergency Service in the Santa Creu i Sant Pau Hospital in Barcelona and co-author of the consensus, agrees on the reasons that made this document necessary. "In the first place, there is a great diversity of immunoassay methods to measure Tnc, with different decision values ​​and different diagnostic performance. This situation can generate errors in the interpretation of Tnc values ​​if the doctor evaluating the patient does not know the characteristics of the method available in his centre," he explains, before adding that it is necessary to reach an agreement on what Tnc concentrations are significant from the clinical point of view. "For the Emergency Physician, the main objective is to avoid inappropriate discharges (avoid false negatives), while for the cardiologist it is important to admit patients with a high probability of AMI (avoid false positives)", concludes Dr. Alquézar.

High sensitivity methods

Given that the absence of elevated Tnc allows one to rule out the existence of myocardial damage, the current challenge for the clinical use of the biomarker is to shorten the observation times to rule out AMI in those patients who do not present it. This shortening of observation times is achieved by measuring the Tnc with so-called high sensitivity methods (Tnc-hs). "The measurement of cardiac troponin (Tnc) is available in practically all healthcare centres involved in the diagnosis or exclusion of myocardial infarction. Another thing is what happens with the measurement of high sensitivity troponin (Tnc-hs), which is widely implemented in tertiary hospitals, but not so much in other levels of care," explains Dr. Jordi Ordóñez, member of the Spanish Society of Laboratory Medicine and senior consultant in Clinical Biochemistry at the Hospital de la Santa Creu i Sant Pau.

"In this sense," he explains, "given the greater sensitivity of the Tnc-hs to detect myocardial damage, this measure should be used systematically in these evaluations. However, not all centres have the necessary equipment to measure Tnc-hs. For this reason, this consensus deals with the advantages and disadvantages of using both the Tnc measurement with high sensitivity methods and with the pre-existing methods, which are still in use ".

"Currently, methods are being developed with even greater sensitivity than those of high sensitivity, which could identify with almost 100% security if a patient does not have an AMI at the time or two hours after the onset of symptoms," concludes the specialist.

What does the measurement of cardiac troponin contribute to the clinic?

Tnc is a biomarker that increases in blood when the heart muscle (myocardium) suffers damage. The precision and analytical sensitivity of the methods to measure Tnc have improved from the first generation of reagents (developed 25 years ago) to the most recent ones, called high sensitivity, which allow for the detection of even minimal myocardial damage.

When Tnc is measured with a high sensitivity method, a normal result of it in serial samples (e.g. at admission and at 1-2 hours), allows us to rule out an AMI with very high probability in a patient with chest pain (thoracic pain). The security of being able to discharge a patient who has suffered an episode of chest pain and shows a normal Tnc result is the main contribution of Tnc to the clinic. Given that the majority of patients who consult in the Emergency Room for chest pain do not have an AMI, their early, safe discharge improves the functioning of saturated emergency services.

The elevation of Tnc in successive blood samples indicates an AMI if the patient's symptoms and/or electrocardiogram are compatible with this diagnosis. However, Tnc also rises in numerous heart diseases, other than AMI, and extra-cardiac issues, which cause damage to the heart by mechanisms other than infarction. This may cause some diagnostic uncertainty for AMI with unclear clinical signs, but the value of Tnc is always of clinical importance because its increases, whatever their cause, are associated with a high risk of complications and require careful evaluation of patients. 

About the Spanish Society of Laboratory Medicine (SEQC^ML)

The Spanish Society of Laboratory Medicine (SEQC^ML) -founded in 1976- now includes more than 2,500 professionals and has as its main objective to bring together all scientists interested in the field of Laboratory Medicine, promote the dissemination of scientific and technical publications, organize meetings, courses and congresses of national and international character, cooperate with other Scientific Societies, and defend and promote the specialties in the field of Laboratory Medicine as well as its associates. Likewise, the Society aims to contribute to the study and recommendation of methods and guidelines, and to establish guidelines and recommendations for training in the field of Laboratory Medicine. For more information: www.seqc.es

About the Spanish Society of Cardiology (SEC)

The Spanish Society of Cardiology (SEC) is a scientific and professional non-profit organization dedicated to increasing the state of knowledge about the heart and circulatory system, to advance in the prevention and treatment of their diseases, and to improve survival and quality of life of cardiac patients.

The SEC has among its main objectives to reduce the adverse impact of cardiovascular diseases and promote better cardiovascular health among the public. To this end, it works to contribute to an improvement in quality of care, promote cardiovascular education and research, promote cardiovascular health and prevention, as well as create national and international links with homologous societies, and represent all professionals interested in the area of cardiology.

About the Spanish Society of Urgent and Emergency Medicine (SEMES)

The Spanish Society of Urgent and Emergency Medicine (SEMES) aims to promote the existence of assistance systems for urgent care and health emergencies that provide coverage to the entire population, provide ongoing training of health and non-health personnel, ensure the quality and dissemination of knowledge to health, non-health, and general population personnel, promote research in urgent care and emergency assistance, and to promote excellence, quality and safety in Emergency Services and Urgent Care in Spain. SEMES, has more than 11,000 members among doctors, nurses and health technicians spread throughout Spain and Latin America. More information at www.semes.org.