A new “fluid biopsy” technique that could identify patients at high risk of a heart attack by identifying specific cells as markers in the bloodstream has been developed by a group of researchers at The Scripps Research Institute (TSRI).
The technique, which is described in the latest edition of IOP Publishing’s journal Physical Biology, works by identifying circulating endothelial cells (CECs) and has been successful in distinguishing patients undergoing treatment for a recent heart attack with a healthy control group.
The researchers believe the technique can now be tested on patients who exhibit symptoms but are yet to experience a heart attack. Currently, there is no predictive test for a heart attack—at least not of satisfying accuracy.
“The goal of this paper was to establish evidence that these circulating endothelial cells can be detected reliably in patients following a heart attack and do not exist in healthy controls—which we have achieved,” said TSRI Associate Professor Peter Kuhn, who led the study. “Our results were so significant relative to the healthy controls that the obvious next step is to assess the usefulness of the test in identifying patients during the early stages of a heart attack.”
Endothelial cells, which line the walls of the arteries, have been strongly linked to ongoing heart attacks when circulating in the bloodstream; they are thought to arrive there when diseased plaque builds up, ruptures and ulcerates, causing inflammation in the arteries. This damage can cause blood clots to form that prevent blood from flowing through the arteries and ultimately results in a heart attack.
As such, the researchers developed a procedure called the High-Definition Circulating Endothelial Cell (HD-CEC) assay to detect and characterise CECs in the blood samples of 79 patients who had experienced a heart attack at the time of sampling.
For comparison, they also used the assay on two control groups, which consisted of 25 healthy patients and seven patients undergoing treatment for vascular disease.
The assay was able to identify CECs by their morphological features and their reactions with specific antibodies. The cells were shown to be significantly elevated in the heart attack patients compared to the healthy controls and were detected with high sensitivity and high specificity.
The researchers also compared their results with a commercially available test, called CellSearch®, which has previously been approved by the U.S. Food and Drug Administration (FDA) to enumerate circulating tumour cells in cancer patients.
The HD-CEC test showed a higher specificity for CECs compared to CellSearch® because it used a direct analysis method and was free of bias from an enrichment stage. “Our assay effectively analyzes millions of cells, which is more work but guarantees that you are analysing all of the potential cells,” said Kuhn.
The first authors of the paper, “Fluid phase biopsy for detection and characterization of circulating endothelial cells in myocardial infarction,” are Kelly Bethel of Scripps Clinic and Madelyn S Luttgen of TSRI. In addition to Kuhn, Bethel and Luttgen, authors include Samir Damani and Sarah Topol of TSRI and Scripps Translational Science Institute; Anand Kolatkar, Rachelle Lamy and Mohsen Sabouri-Ghomi of TSRI; and Eric J Topol of Scripps Clinic, TSRI and Scripps Translational Science Institute. After January 10, this paper can be downloaded fromhttp://iopscience.iop.org/1478-3975/11/1/016002/article.
The work in this paper was supported by Award Number 3UL1RR025774-02S1 from the National Center for Research Resources and Award Number U54CA143906 from the National Cancer Institute.
Adapted from a news release issued by Scripps Research Institute
Re http://iopscience.iop.org/1478-3975/11/1/016002/article
Few points to enlighten those interested on the subject :
A- Circulating Endothelial cells originates from any location (any vessel) rather than heart(coronary) vessels , any body with atherosclerotic disease of vessels any part of his/her body will likely release”shower” these endothelial cells to the circulation after the ıschemıc event at that locatıon , since you can NOT differentiate the “origin” of these endothelial cells the test has `NO SPECIFICITY` . Endothelial cell can come from any vessel from any ıschemic part of the the body(tissue) rather than heart vessels ..
B- Since the research is done among people who had already major ischemic coronary event with anticoagulation and partial and/or complete revascularization and `RELEASE OF ENDOTHELIAL CELLS` from the ischemic vessel walls to the circulation ; in other words after the fact (ischemic damage) of cardiac event the test will have NO PREDICTIVE VALUE whatsoever to detect the significant amount of circulating free endothelial cells PRIOR TO ISCHEMIC EVENT , since the amount of circulating endothelial cells strictly correlates with the `ischemic event ` and without ischemia there would not be significant enough circulating endothelial cells to detect .
C- The `plaque rupture` event is a `sudden event` followed with immediate thrombosis `within minutes` followed with ischemia , and in fact the release of endothelial cells are after the fact with reasonable revascularization of ischemic area vessels ..Though atherosclerotic stenosis of the vessels frequently give predictive `clinical symptoms` prior to event of ultimate `occlusion` of the vessel ‘ it is highly questionable that the so called` unstable angina` will also release significant amount of `CEC` circulating endothelial cells that can be detected with the test and MORE reasonable clinical application and differentiation `predictive` value for the coronary event .. This needs to be tested clinically in the future of course on the large group of “unstable angina patients “ with good controls .
So the bottom line is the value of the test strictly depends on the `predictive value ` of the test if it does really exists ? among `unstable angina` patients . And predicting in any event beforehand is NOT that easy , like familiar good old Stock Market ; simply you can not predict the specific timing of the event with reasonable accuracy . Unless you are a `inside trader` it means cheating . Similar analogy unless we have `insider` looking at the `Coronary vessels and endothelial lining of vessels ` at ALL TIMES , simply we can NOT accurately predict the coronary event yet clinically … BUT again it may have potential differential diagnostic and/or predictive value –hopefully- ( unstable angina or unusual clinical presentations of ischemic cardiac or other ischemic events ) rather than after the fact testing which is done here .
Thank you
Metin Gunduz,M.D. ABEM