The Evolution of Cardiac Biomarkers: What’s on the Horizon?

March 24, 2010

ecgRushi Parikh

Faculty peer reviewed

Cardiac biomarkers have historically been a mainstay of the diagnostic criteria of acute coronary syndrome (ACS). Previously utilized cardiac biomarkers include aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and myoglobin; now more often troponin and to a lesser extent creatine kinase-MB are the principal biomarkers used to diagnose ACS.1

Myocardial necrosis and the subsequent loss of cardiomyocyte membrane integrity lead to the release of cardiac biomarkers into the peripheral circulation. Biomarkers, however, do not indicate the cause of myocardial necrosis, and therefore the diagnosis of ACS requires positive biomarkers in the context of ischemic symptoms and/or dynamic EKG changes. Effective biomarkers are specific to myocardial tissue; are released into the circulation within an appropriate diagnostic window and in proportion to the degree of myocardial injury; and are quantifiable via a fast, inexpensive, and reproducible assay.1

Serially-drawn troponin currently is the most useful cardiac biomarker for identifying ACS, given its sensitivity and specificity with respect to time course. However, a significant limitation of troponin is its poor sensitivity within the first 6 hours after symptom onset and a possible 12-hour delay in detection.1 Clearly, a more sensitive cardiac biomarker is needed during the immediate period following symptom onset in order to improve early diagnosis of ACS.

A potential solution under recent investigation is heart-type fatty acid binding protein (H-FABP), a small cytoplasmic protein that serves as the chief transporter of long-chain fatty acids in cardiomyocytes. H-FABP is abundantly found in cardiomyocytes, but it is also less commonly seen in skeletal muscle, the distal tubules of the kidney, and the brain. Following myocardial necrosis, H-FABP is quickly released into the circulation and can be detected within an hour. It usually peaks within 4 hours and is generally undetectable after 24-36 hours. Notably, this release and kinetics pattern is similar to that of myoglobin, but H-FABP’s specificity for cardiac muscle is significantly higher than that of myoglobin, making it the more specific cardiac biomarker.2

Several clinical studies suggest that H-FABP is superior to troponin in the early detection of myocardial necrosis. A 2003 study of 371 consecutive ER patients presenting with chest pain, in which 37 of 68 patients arriving within 2 hours of symptom onset had a diagnosis of myocardial infarction (MI), showed that H-FABP sensitivity/specificity was 89%/52% (H-FABP cutoff of 7 ng/ml) in comparison to troponin-T (Tn-T) sensitivity/specificity of 22%/94% (Tn-T cutoff not reported). Both H-FABP’s higher sensitivity and Tn-T’s higher specificity were statistically significant.2 A similarly designed 2008 multicenter study of 419 ER patients with suspected ACS presenting within 3 hours of symptom onset demonstrated that of the 148 patients diagnosed with MI, H-FABP sensitivity/specificity was 60%/88% (H-FABP cutoff of 6.2 ng/ml) whereas Tn-T sensitivity/specificity was 19%/99% (Tn-T cutoff not reported). H-FABP’s higher sensitivity was again statistically significant, but Tn-T’s higher specificity was not.3 Other similar studies in the literature corroborate these findings.

H-FABP appears to be a more effective cardiac biomarker than troponin in early detection of ACS. Notwithstanding these encouraging preliminary data, further multicenter studies must be conducted using standardized H-FABP and troponin assays before H-FABP can be seriously considered as a clinical tool for the early diagnosis of ACS.

Rushi Parikh is a 4th year medical student at NYU School of Medicine.

Peer reviewed by Adam Skolnick MD

References
1. Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2007;50:e1-e157. (http://www.acc.org/qualityandscience/clinical/topic.htm)
2. Seino, Y, Ogata K, Takano T, et al. Use of a whole blood rapid panel test for heart-type fatty acid-binding protein in patients with acute chest pain: comparison with rapid troponin T and myoglobin tests. Am J Med. 2003;115(3):185-190.
3. Valle H, Riesgo LG, Bel MS, Gonzalo PE, Sanchez MS, Oliva LI. Clinical assessment of heart-type fatty acid binding protein in early diagnosis of acute coronary syndrome. Eur J Emerg Med. 2008;15(3):140-144.

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