Investigators at Scripps Translational Science Institute, La Jolla, think they have moved one step closer to a test to predict an impending myocardial infarction. Topol and colleagues published their results in Science Translational Medicine.¹ Their approach might give up to 2 weeks’ notice that an individual is at serious risk for suffering an MI.

The technique involves tracking circulating endothelial cells (CECs) using an automated and clinically feasible CEC three-channel fluorescence microscopy assay. Normally, CECs coat the inside of heart arteries, but a chain reaction can begin with CECs flaking off the interior wall of an artery and gradually creating a crack that attracts a blood clot. According to Eric Topol, MD, chief academic officer at Scripps Health, “When (CECs) start to slough off, become numerous [and] misshapen, and have multiple nuclei, it is [a] sign that a heart attack is imminent.”

The Scripps team evaluated this biomarker in 50 consecutive patients with ST-segment elevation MI and 44 consecutive healthy controls. CEC counts were significantly elevated in MI cases versus controls, with median numbers of 19 and 4 cells/mL, respectively. A receiver-operating characteristic (ROC) curve analysis demonstrated an area under the ROC curve of 0.95, suggesting near-dichotomization of MI cases versus controls.

They observed no correlation between CECs and typical markers of myocardial necrosis (creatine kinase, troponin). Morphological analysis of the microscopy images of CECs revealed a 2.5-fold increase (p <0.0001) in cellular area and a 2-fold increase (p <0.0001) in nuclear area of MI CECs versus healthy controls, age-matched CECs, as  well as CECs obtained from patients with pre-existing peripheral vascular disease.

The distribution of CEC images that contained from 2 to 10 nuclei demonstrates that MI patients were the only subject group to contain more than 3 nuclei per image, indicating that multicellular and multinuclear clusters are specific for acute MI.

Test Desperately Needed

The tests could potentially address "the greatest unmet need" facing cardiologists, according to Dr. Topol. In an interview with the Los Angeles Times, he called the phenomenon the "Tim Russert syndrome," referring to the host of NBC’s “Meet the Press” who died of a heart attack in 2008, weeks after undergoing a stress test with apparently normal results.

"When someone is having the real deal, we know that," Dr. Topol said. "The real question is, is something percolating in their artery? We'd like to prevent the heart attack from happening," or at least mitigate its effects with drugs. Acute MI remains highly unpredictable despite recent advances in the diagnosis and treatment of coronary artery disease. Accordingly, a clinical measurement that can predict an impending MI is desperately needed.

The new study indicates that CEC counts may serve as a promising clinical measure for the prediction of atherosclerotic plaque rupture events.

Reference

1. Damani S, Bacconi A, Libiger O, et al. Characterization of circulating endothelial cells in acute myocardial infarction. Sci Transl Med 2012;4:126ra33.

 

Keywords: Coronary Artery Disease, Myocardial Infarction, Plaque, Atherosclerotic, Creatine Kinase, Translational Medical Research, Peripheral Vascular Diseases, Biomarkers, Thrombosis, Cardiovascular Diseases, ROC Curve, Microscopy, Fluorescence, Endothelial Cells, Troponin, Exercise Test

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