3 Clinical need and practice

The problem addressed

3.1 Cardiac troponin I and cardiac troponin T are biological markers of cardiac muscle death (cardiomyocyte necrosis). They are released into the circulation when damage to cardiac muscle has occurred. Troponins C, I and T form the troponin‑tropomyosin complex which is responsible for regulating cardiac muscle contraction. Troponins I and T are the recommended biomarkers for diagnosing myocardial infarction (MI) in Chest pain of recent onset (NICE clinical guideline 95), when a rise and fall in troponin levels can signify that myocardial damage has occurred. The optimum sensitivity of non‑high‑sensitivity troponin assays (hereafter referred to as standard troponin assays) for acute MI occurs 10–12 hours after the onset of symptoms. For many people, this results in the need for hospital admission and observation while serial troponin testing is carried out. To overcome this, high‑sensitivity troponin assays have been developed. These are able to detect lower levels of troponin in the blood earlier than older standard assays, leading to improved early detection of acute MI.

3.2 Using these high-sensitivity assays enables earlier detection of changes in troponin levels. This allows non-ST-segment elevation myocardial infarction (NSTEMI) to be ruled out within 4 hours, if test results are available within 3 hours of presentation to the emergency department. The increased sensitivity of these assays could mean a shorter inpatient hospital stay for people without raised levels of troponin and earlier intervention for those with a confirmed NSTEMI. As with older standard troponin assays, the high-sensitivity assays are intended to be used with clinical history taking and the electrocardiogram to diagnose NSTEMI because, despite being highly specific for cardiomyocyte necrosis, troponin may also be raised in people who do not have underlying evidence of ischaemic heart disease. Conditions other than acute MI that may cause troponin levels to be raised include myocarditis, congestive heart failure, severe infections, musculoskeletal conditions and renal disease.

3.3 The purpose of this assessment is to evaluate the clinical and cost effectiveness of the Elecsys Troponin T high‑sensitive, ARCHITECT STAT High Sensitive Troponin‑I and the AccuTnI+3 assays for early rule out or diagnosis of acute MI (without ST‑segment elevation). In this assessment, the timing of testing is within 4 hours of people presenting to an emergency department with acute chest pain.

The condition

3.4 Acute MI is part of a group of conditions collectively known as acute coronary syndrome, which includes ST‑segment‑elevation myocardial infarction (STEMI), NSTEMI, and unstable angina. These conditions are associated with common symptoms but have different underlying pathologies. STEMI is usually associated with a relatively large amount of damage to the myocardium (heart muscle) caused by a major blockage in the coronary artery, and can be detected from ST‑elevation on an electrocardiogram (ECG) trace. By comparison, NSTEMI is often associated with relatively less damage to the myocardium, caused by either partial blockage of the coronary artery or blockage of a smaller artery, and does not produce ST‑elevation on ECG. Angina occurs because of narrowing of the coronary arteries, and a consequent reduction in blood flow to the heart. Angina may be considered unstable when chest pain is not relieved by rest or medications used for stable angina.

3.5 Acute coronary syndromes arise when blood flow is restricted in the coronary arteries, usually caused by atherosclerosis, a build‑up of plaque. When blood flow to the heart is reduced or blocked for a significant length of time (around 30–60 minutes), damage to cardiomyocytes (heart muscle cells) occurs resulting in the release of cardiac troponin. This is a pathological change and the consequent rise and/or fall in troponin levels can distinguish an acute MI from unstable angina.

3.6 People with acute coronary syndrome generally present with chest pain, a symptom that is responsible for around 700,000 emergency department attendances per year in England and Wales, and 253,765 emergency admissions per year. During 2011/12, the Myocardial Ischaemia National Audit Project reported 79,433 admissions with acute MI recorded in England and Wales, 32,439 (41%) of which were categorised as STEMI and 46,994 (59%) of which were categorised as NSTEMI. The incidence of acute MI increases with age, with the average age of first STEMI being 65 years, and of first NSTEMI 70 years. The incidence of acute MI is also reported to be greater among men than women.

The diagnostic and care pathways

3.7 People with acute coronary syndrome often present with acute chest pain and other symptoms such as nausea, vomiting, dyspnoea, sweating and indigestion. These symptoms, including acute chest pain, are common to many other conditions such as anxiety, gastro‑oesophageal reflux disease and muscle strain. If clinical assessment suggests a significant probability of acute coronary syndrome then investigations are carried out as described in NICE clinical guideline 95. Initial assessment comprises:

  • taking a resting 12‑lead ECG along with a clinical history, a physical examination and biochemical marker analysis

  • managing people in whom regional ST‑segment elevation or presumed new left branch bundle block is observed on ECG according to Myocardial infarction with ST-segment elevation (NICE clinical guideline 167).

3.8 People without persistent ST‑elevation changes on ECG are given a working diagnosis of a suspected non‑ST‑segment‑elevation acute coronary syndrome, and need further testing with biochemical marker analysis to distinguish NSTEMI from unstable angina, conditions that need different treatment. NICE clinical guideline 95 makes the following recommendations on the use of biochemical markers and refers to the use of troponin tests during a 10–12 hour period:

  • Take a blood sample for troponin I or troponin T on initial assessment in hospital. These are the preferred biochemical markers to diagnose acute MI.

  • Take a second blood sample for troponin I or T measurement 10–12 hours after the onset of symptoms.

  • Do not use biochemical markers such as natriuretic peptides and high sensitivity C‑reactive protein to diagnose acute coronary syndrome.

  • Do not use biochemical markers of myocardial ischaemia (such as ischaemia modified albumin) as opposed to markers of necrosis when assessing people with acute chest pain.

  • Take into account the clinical presentation, the time from onset of symptoms and the resting 12‑lead ECG findings, when interpreting troponin measurements.

3.9 Guidelines from the European Society of Cardiology on the management of people with a suspected non-ST-segment elevation acute coronary syndrome acknowledge the use of high‑sensitivity troponin assays and make recommendations on the use of a fast‑track rule‑out protocol. The guidelines state that high‑sensitivity troponin assays have a negative predictive value of greater than 95% for acute MI on admission; including a second test at 3 hours can increase this to 100%.

3.10 It is recommended that a diagnosis of NSTEMI should be made using the universal definition of MI. The third universal definition of myocardial infarction defines acute MI as "the detection of a rise and/or fall of cardiac biomarker values (preferably cardiac troponin) with at least one value above the 99th percentile upper reference limit and with at least 1 of the following: symptoms of ischaemia; new or presumed new significant ST‑segment‑T wave changes or new left branch bundle block; development of pathological Q waves in the ECG; imaging evidence of new loss of viable myocardium or new regional wall motion abnormality; or identification of an intracoronary thrombus by angiography or autopsy."

3.11 The management of people with a suspected NSTEMI or unstable angina is described in Unstable angina and NSTEMI (NICE clinical guideline 94). Initial treatment includes a combination of antiplatelet (aspirin, clopidogrel and glycoprotein IIb/IIIa inhibitors) and antithrombin therapy, taking into account contraindications, risk factors and the likelihood of percutaneous coronary intervention.

3.12 People with a suspected non‑ST‑segment elevation acute coronary syndrome are often transferred out of the emergency department to a range of clinical areas depending on the likelihood of complications and adverse outcomes. Established risk scores, such as the GRACE score or the TIMI risk score, that predict 6‑month mortality can be used in combination with ECG findings and initial cardiac biomarker analysis to stratify people with a suspected non‑ST‑segment elevation acute coronary syndrome. The care settings available vary between hospitals, but are likely to include coronary care, acute medical, chest pain and clinical decision units. People in whom a raised troponin level is not observed may be discharged for further follow up according to clinical judgement and, in some cases, the results of ischaemia testing.

3.13 It is recommended that people who have a diagnosis of NSTEMI, and who are assessed as being at low risk of future complications, have conservative treatment with aspirin and/or clopidogrel, or aspirin plus ticagrelor. Ischaemia testing is also recommended to identify people who may need further intervention. In addition, people at a higher risk of future complications may also have coronary angiography (within 96 hours of admission) with subsequent coronary revascularisation by percutaneous coronary intervention or coronary artery bypass grafting when indicated (NICE clinical guideline 94).

3.14 Longer‑term follow up of people who have had an acute MI (including both STEMI and NSTEMI) is described in full in Myocardial infarction: secondary prevention (NICE clinical guideline 172). This includes recommendations on lifestyle changes, cardiac rehabilitation programmes, drug therapy (including a combination of angiotensin converting enzyme inhibitors, aspirin, beta‑blockers and statins), and further cardiological assessment to determine whether coronary revascularisation is needed.

  • National Institute for Health and Care Excellence (NICE)