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H-FABP Immunoturbimetric Assay with troponin testing for the assessment of heart-related chest pain

Source agency:

NIHR-HSC

Date of Submission:

01/08/2012

Date of Printing:

20/05/2013

Disclaimer:

This report is work in progress and should not be used for external distribution without permission from the originating agency. Users should be aware that reports are based on information available at the time of research and often on a limited literature search.

Technology, Company & Licensing

Technology name:

H-FABP Immunoturbimetric (IT) Assay

Technology - description:

Randox Laboratories Ltd’s H-FABP IT Assay is a diagnostic test intended to be used for patients who have suspected ACS. The test is intended to be performed in a hospital laboratory on a sample of blood taken from the patient when they first enter the hospital emergency department and in combination with a troponin test. Tests for H-FABP that used a different format (Randox Biochip, ELISA and point of care) have been available previously, but according to an expert have not been widely adopted. The H-FABP IT Assay is the first test for fully quantifying the amount of H-FABP in the blood that can be run on a range of standard equipment that may already be available in a hospital laboratory. In practice there may be a number of different ways the test could be used and interpreted.

H-FABP is a protein found in heart cells and its presence in blood may be an indicator that someone has damage to their heart. The H-FABP molecule is smaller than troponin and unbound within the cell, meaning it may be released into the bloodstream earlier following restriction of oxygen to the heart. In combination with a troponin test, the H-FABP IT Assay may help to rule out ACS at an earlier stage and may also be of use in identifying people with ACS who are at high risk of having a heart attack or dying from cardiovascular causes over the next few months.

The H-FABP IT Assay can be performed on blood serum or blood plasma which has been separated from whole blood. The assay uses latex particles coated with antibodies against H-FABP (mouse monoclonal anti-H-FABP antibodies) which bind to any H-FABP present in the sample. This generates cloudiness (turbidity) in the sample the degree of which can then be measured by the amount of light the sample absorbs. The concentration of H-FABP in the sample can then be determined from this measurement.

Company or developer:

Randox Laboratories Ltd.

Reason for database entry:

The H-FABP IT Assay is the first test for fully quantifying the amount of H-FABP in the blood that can be run on a range of standard equipment that may already be available in a hospital laboratory.

Technology - stage in early warning process:

Assessment complete

Technology - stage of development:

Other

Licensing, reimbursement and other approval:

The H-FABP IT Assay was CE marked in June 2011 and was made commercially available in the UK in October 2011. The company state that a service delivery validation is taking place in six hospital trusts across the UK.

Technology - type(s):

Diagnostics

Technology - use(s):

Diagnostic

Patient Indication & Setting

Patient indications:

People who have suspected acute coronary syndrome (ACS).

Disease description and associated mortality and morbidity:

Acute coronary syndrome (ACS) is the name given to a group of heart conditions caused by insufficient blood supply to the heart. ACS includes heart attack (myocardial infarction); when blood flow to part of the heart is blocked for long enough that part of the heart muscle is damaged or dies, and unstable angina; where the blood supply to the heart is restricted and symptoms develop rapidly (1,2,3).

Symptoms of ACS include pain in the chest and/or other areas, for example the arms, back or jaw, lasting longer than 15 minutes and nausea, vomiting, sweating, breathlessness or a combination of these. Not all people with an ACS have central chest pain as the main feature(4). ACS is usually caused by the build up of plaque, made up of cholesterol and other material, on the inner walls of blood vessels which supply the heart with blood (the coronary arteries). In a large proportion of cases an ACS episode is caused by the rupture or erosion of a plaque leading to the formation of a blood clot which in turn leads to insufficient blood supply to the heart(4,5).

Number of Patients:

Between 20% and 40% of people will experience chest pain or discomfort at some point, resulting in around 1% of primary care consultations, 5% of emergency department attendance, and 40% of emergency hospital admissions(6). Between April 2010 and April 2011 there were just over 92,000 heart attacks in England. Most heart attacks occur in people over 45 years of age and men are two to three times more likely to have a heart attack than women(7).

Technology - specialities(s):

Emergency care, Cardiovascular disease & vascular surgery

Technology - setting(s):

General hospital and ambulatory care, Specialist hospital

Setting - further information:

Hospital Emergency Department

Impact

Alternative and/or complementary technology:

Additive or complementary technology

Current Technology:

Conditions causing chest pain or discomfort, such as ACS or angina, may lead to death or disability. This emphasises the importance of quick and accurate diagnosis, particularly as treatments are available to improve symptoms and prolong life. If a heart attack is suspected a person should be admitted to hospital immediately(7). The British Cardiovascular Society recommends that patients presenting with acute heart conditions should be managed by a specialist, multi-disciplinary cardiac team(8).
Current strategies to diagnose when someone has had a heart attack include taking the clinical history, physical examination, conducting an electrocardiogram (ECG) - to look for changes in the electrical activity of the heart - and blood tests to look for substances (biomarkers) released when there has been damage to the heart muscle. Testing for a protein called cardiac troponin (cTn) is preferred over testing for other biomarkers(9). One expert suggests that troponin testing is particularly useful when there are no obvious changes on an ECG.

Two different parts of the troponin protein can be measured, troponin I (cTnI) and troponin T (cTnT). The choice of which is measured depends on the laboratory equipment available.

The current National Institute for Health and Clinical Excellence (NICE) guideline recommends that people with suspected ACS have an ECG and a blood test for troponin I or T levels on arrival in hospital. It also recommends a second blood test for troponin I or T levels is performed 10-12 hours after the onset of symptoms and that the physical signs or symptoms, time from onset of symptoms and the ECG findings should be taken into account when interpreting troponin tests(4). The initial troponin test allows subsequent changes in troponin levels to be assessed.

Recently high-sensitivity or ultrasensitive troponin assays (hsTnI and hsTnT) have become available and are widely used. With older troponin tests, there may have been a delay of up to 12 hours before the test was optimal for diagnosing ACS. Thus, there may have been a delay before a diagnosis could be made meaning someone had to be admitted to hospital and possibly delaying treatment. However, newer high-sensitivity troponin tests can detect lower levels of troponin and therefore, heart attack can now be detected more frequently and earlier in patients with chest pain. European guidelines suggest high-sensitivity troponin tests can be performed on presentation and then again three hours later as part of a strategy to rule out ACS(6,10,11). High-sensitivity troponin tests may have improved the ability to identify people with ACS at an early stage (increased sensitivity), but this may be at the expense of producing more false positives (loss of specificity)(6).

Health Impact:

Cardiovascular diseases are currently the leading cause of death in industrialised countries and despite modern treatment, the rates of death, heart attack, and re-admission of patients with ACS remain high(10). If untreated ACS has a poor outlook and high death rate particularly in people who have had damage to their heart muscle. Accurate diagnosis allows the appropriate use of drugs or surgical treatment and is important for the prevention of future cardiovascular events including heart attack, stroke, repeat surgery or death(22).

Adding the H-FABP IT Assay to current tests may improve the ability to rule out ACS at an earlier stage. The test may also be useful in assessing someone’s risk of having serious heart-related events in the future.

Diffusion:

 

Cost, infrastructure and economic consequences:

The cost of each test is approximately £5 (depending on how many tests are performed).

Ethical, social, legal, political and cultural impact:

 

Evidence & Policy

Clinical evidence and safety:

The role of H-FABP tests in the assessment of heart-related chest pain in an emergency department has been investigated in a number of studies. Two recent systematic reviews including H-FABP studies, published in the past year, are summarised below. There are currently no published studies which examine the benefits of using the H-FABP IT Assay in UK emergency departments.

One systematic review and meta-analysis aimed to estimate the accuracy of H-FABP testing in diagnosing heart attack(11). The review’s authors included four studies which reported the accuracy of the combination of a troponin and an H-FABP test in the diagnosis of heart attack(12,13,14,15). The tests were performed at presentation and the combination was considered positive if either test was positive. The authors of the review state the addition of H-FABP to troponin increased the sensitivity from 42-75% to 76-97% but decreased specificity from 94-100% to 65-93%. They note that further studies are required to assess whether a negative troponin combined with negative H-FABP assay (when combined with ECG) on admission would allow early discharge of patients. The review’s authors limited their analysis to studies that looked at the diagnosis of heart attack, but state there is some evidence that H-FABP predicts adverse outcome in troponin negative patients with suspected ACS. They concluded further research is needed to address how adding H-FABP tests to newer high sensitivity troponin tests impacts on the ability to diagnose heart attack at an early stage.

Another systematic review examined the evidence of effectiveness of novel biomarkers in diagnosing ACS in patients presenting to emergency departments or chest pain clinics with chest pain or symptoms suggesting reduced blood supply to the heart(16). The review included two studies which showed improved sensitivity when an H-FABP test was used in combination with a troponin test(13,14). The review’s authors state the combination with TnI improved sensitivity from 71% (95% CI 57-83%) to 97% (95% CI 86-99%) and the combination with TnT from 91% (95% CI 83-95%) to 98% (95% CI 91-99). They do not report the effect on specificity.

Two relevant narrative reviews have also been published in the past year. One examining the role of H-FABP in ACS(17) and the other of biomarkers in acute myocardial injury(18).

In 2011 NHS Evidence produced an Evidence Update on Chest Pain which mentions H-FABP testing(6).

Randomised controlled trials where patient management is guided with or without H-FABP tests would provide the strongest evidence as to whether adding H-FABP tests to hsTn brings clinical benefits. Such trials are awaited.

Economic evaluation:

A review into the cost-effectiveness of diagnostic strategies for suspected ACS by the NIHR Health Technology Assessment Programme is currently in progress and is due to be published in December 2012 (19).

Ongoing research:

Two studies examined the combination of H-FABP, hsTn and ECG in diagnosing heart attack in patients with chest pain at two English emergency departments. Preliminary data from these studies has been reported in conference abstracts(20,21). An economic evaluation is included in which, the authors state, when combined with hsTn troponin and ECG, H-FABP “has potential to reduce unnecessary admissions and healthcare costs” without an increase in major adverse cardiac events.

Ongoing or planned HTA:

 

Web link:

http://www.nhsc-healthhorizons.org.uk/topics/h-fabp-immunoturbimetric-assay-with-troponin-testi/

References and sources:

1. PubMed Health. A.D.A.M Medical Encyclopedia. Heart attack. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001246/ Accessed 24 May 2012.

2. NHS Choices. Angina. http://www.nhs.uk/conditions/Angina/Pages/Introduction.aspx Accessed 24 May 2012.

3. Patient UK. Acute coronary syndrome. http://www.patient.co.uk/health/Acute-Coronary-Syndrome.htm Accessed 24 May 2012.

4. National Institute for Health and Clinical Excellence. Chest pain of recent onset: assessment and diagnosis of recent onset chest pain or discomfort of suspected cardiac origin. Clinical guideline CG95. London: NICE; March 2010.

5. MedlinePlus. Coronary artery disease. http://vsearch.nlm.nih.gov/vivisimo/cgi-bin/query-meta?v%3Aproject=medlineplus&query=coronary+atherosclerosis&x=12&y=13 Accessed 17 May 2012.

6. NHS Evidence. Chest Pain – 2011 Evidence Update. https://www.evidence.nhs.uk/

7. NHS Choices. Heart attack. http://www.nhs.uk/conditions/heart-attack/pages/introduction.aspx Accessed 8 June 2012.

8. British Cardiovascular Society. From coronary care unit to acute cardiac care unit – the evolving role of specialist cardiac care. Recommendations of the British Cardiovascular Society Working Group on Acute Cardiac Care. October 2011.

9. University of Oxford. Department of Primary Health Diagnostic Horizon Scanning Centre. MaDOx. Horizon Scan Report 0013. Point-of-care test for cardiac troponin. February 2011.

10. European Society of Cardiology Guidelines. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. European Heart Journal 2011; 32: 2999–3054.

11. Carroll C, Khalaf M, Stevens J et al. Heart-type fatty acid binding protein as an early marker for myocardial infarction: Systematic review and meta-analysis. EMJ Online First. Published online first: 16th May 2012.

12. Body R, McDowell G, Carley S et al. A FABP-ulous ‘rule out’ strategy? Heart fatty acid binding protein and troponin for rapid exclusion of acute myocardial infarction. Resuscitation 2011; 82: 1041-6.

13. Haltern G, Peiniger S, Bufe A et al. Comparison of usefulness of heart-type fatty acid binding protein versus cardiac troponin T for diagnosis of acute myocardial infarction. The American Journal of Cardiology 2010; 105: 1-9.

14. McCann C, Glover Ben, Menown I et al. Novel biomarkers in early diagnosis of acute myocardial infarction compared with cardiac troponin T. European Heart Journal 2008; 29: 2843–50.

15. Mion M, Novello E, Altinier S et al. Analytical and clinical performance of a fully automated cardiac multi-markers strategy based on protein biochip microarray technology. Clinical Biochemistry 2007; 40: 1245–51.

16. Lin S, Yokoyama H, Rac V and Brooks S. Novel biomarkers in diagnosing cardiac ischemia in the emergency department: A systematic review. Resuscitation 2012; 83: 684-91.

17. Viswanathan K, Hall A and Barth J. An evidence-based approach to the assessment of heart-type fatty acid binding protein in acute coronary syndrome. The Clinical Biochemist Reviews 2012; 33: 3-11.

18. Kehl D, Iqbal N, Fard A et al. Biomarkers in acute myocardial injury. Translational Research 2012; 159: 252–64.

19. NIHR Health Technology Assessment Programme. Cost-effectiveness of diagnostic strategies for suspected acute coronary syndrome (ACS). http://www.hta.ac.uk/2269 Accessed 11 June 2012.

20. Body R, Carley S, Burrows G et al. Combining heart fatty acid binding protein and high sensitivity troponin in the emergency department. Abstract 84 presented at 14th International Conference on Emergency Medicine. Academic Emergency Medicine 2012; 19: 748-49.

21. Body R, Dixon D, Burrows G et al. Economic evaluation of a heart-type fatty acid binding protein based protocol for rapid chest pain assessment. Abstract 79 presented at 14th International Conference on Emergency Medicine. Academic Emergency Medicine 2012; 19: 746-7.

22. National Institute for Health and Clinical Excellence. Unstable angina and NSTEMI. The early management of unstable angina and non-ST-segment-elevation myocardial infarction. Clinical guideline CG94. London: NICE; March 2010.

Notes: