Transcript

Welcome to AACC’s Expert Access Live Online program

Multimarker Strategies For Myocardial Ischemia: The Next And Smarter Generation Of Test Panels

This month's expert is Alan H.B. Wu, PhD. View the presentation and direct your questions to our online expert. AACC would like to thank Bayer HealthCare Diagnostics for making this program possible.

Could you please elaborate on some of the clinical endpoints that should be part of the studies looking at markers/panels for cardiac iscemia?
Miami, FL

Alan H.B. Wu, PhD: In the absence of acute myocardial infarction, i.e., during the presentation, the typical endpoints are short-term (30-day) death, myocardial infarction, need for urgent revascularization or rehospitalization for acute coronary syndrome. In the presence of AMI during the presentation, the objective is to determine if blood testing for ischemia at presentation (and before release of a necrosis cardiac marker) is reliably positive for a patient that eventually becomes positive.

Excellent presentation, Dr. Wu. Do you have an opinion on how results of ischemia panel should be communicated to doctors: as a single "scored" value or as discrete values for each analyte?
Tokyo

Alan H.B. Wu, PhD: This is a question for debate in the future. We may eventually learn from the stroke panel if and when this becomes FDA cleared. My sense is that the laboratory will need to QA/QC individual markers, but if each test alone offers no diagnostic or prognostic value, i.e., the ED physician will only be interested in the aggregate result, i.e., either the patient is ischemic or not. This is the easiest to implement; physicians are not confused by the individual results that have no meaning to them.

Do you have any insight as to how the NHLBI Clinical Proteomics Working Group was put together?
Washington, DC

Alan H.B. Wu, PhD: Sorry, I am not a member of the working group. I presume it was a collaboration between basic scientists interested in proteomics, the pharmaceutics industry, and in vitro diagnostics industry, with interest by the Food and Drug Adminsitration. You are encouraged to read Granger CB. National Heart, Lung, and Blood Institute Clinical Proteomics Working Group Report. Circulation 2004;109(14):1697-1703.

Are any of these ischemia such as IMA and uFFa FDA-cleared as a diagnostic for or aid to diagnosis for myocardial ischemia? Are any of the multimarker panels?
Oklahoma City, OK

Alan H.B. Wu, PhD: The IMA test by itself is FDA-cleared as a test for the rule out of myocardial ischemia, with a negative result. The FDA has asked the manufacturer to determine what a positive result means and clinical trials are underway to answer this question. uFFA is not cleared, and there is no multimarker panel that is cleared for ischemia, although Biosite Diagnostics is working on same.

Alan H.B. Wu, PhD: The IMA test by itself is FDA-cleared as a test for the rule out of myocardial ischemia, with a negative result. The FDA has asked the manufacturer to determine what a positive result means and clinical trials are underway to answer this question. uFFA is not cleared, and there is no multimarker panel that is cleared for ischemia, although Biosite Diagnostics is working on same.

Would any of these markers change my treatment options in cases where there is already clinical indication of ischemia?
Barrington, VT

Alan H.B. Wu, PhD: As with any laboratory test, those for myocardial ischemia are aids to the other information available to the clinician, including clinical presentation, electrocardiogram, echocardiogram where available, stress testing, etc. One might be more agressive if there is biochemical evidence of myocardial ischemia with or without clinical evidence, if the test or panel of tests proves to be useful. We can only hope that an ischemia panel will have the clinical impact that cardiac troponin has had in risk stratification of patients who have minor myocardial necrosis.

Can I use IMA instead of 8-iso prostaglandin F2-A (iP)as a marker of ischemia in patients who develop ST segement elevation during PCI?
Boston, Mass.

Alan H.B. Wu, PhD: There has been one recent study that has addressed this very question. The information is given below. Sinha MK. Gaze DC. Tippins JR. Collinson PO. Kaski JC. Coronary Artery Disease Research Unit, St George's Hospital, London, UK. Ischemia modified albumin is a sensitive marker of myocardial ischemia after percutaneous coronary intervention. Circulation 107(19):2403-5, 2003 May 20. Abstract BACKGROUND: Ischemia modified albumin (IMA; Ischemia Technologies, Inc) blood levels rise in patients who develop ischemia during percutaneous coronary intervention (PCI). It is not known whether IMA elevations correlate with increases in other markers of oxidative stress, ie, 8-iso prostaglandin F2-A (iP). METHODS AND RESULTS: We compared IMA versus iP plasma levels in 19 patients (mean age 62.8+/-11.9 years) undergoing PCI and 11 patients (mean age 64+/-13.6 years) undergoing diagnostic angiography (controls). In the PCI patients, blood samples for IMA and iP were taken from the guide catheter before PCI and after balloon inflations, and from the femoral sheath 30 minutes after PCI. IMA was measured by the albumin cobalt binding (ACB) test and plasma iP by enzyme immunoassay. During PCI, all 19 patients had chest pain and 18 had transient ischemic ST segment changes. IMA was elevated from baseline in 18 of the 19 patients after PCI. Median IMA levels were higher after PCI (101.4 U/mL, 95%CI 82 to 116) compared with baseline (72.8 U/mL, CI 55 to 93; P<0.0001). Levels remained elevated at 30 minutes (87.9 U/mL, CI 78 to 99; P<0.0001) and returned to baseline at 12 hours (70.3 U/mL, CI 65 to 87; P=0.65). iP levels were raised after PCI in 9 of the 19 patients. However, median iP levels were not significantly different immediately (P=0.6) or 30 minutes after PCI (P=0.1). In the control group, IMA and iP levels remained unchanged before and after angiography (P=0.2 and 0.16, respectively). CONCLUSIONS: IMA is a more consistent marker of ischemia than iP in patients who develop chest pain and ST segment changes during PCI.