A national team of researchers, led by a cardiovascular nuclear medicine specialist at the University of Maryland Medical Center, has demonstrated for the first time that an experimental radioactive compound can show images of heart damage up to 30 hours after a brief interruption of blood flow and oxygen. The discovery may help physicians in emergency rooms and in their offices determine whether a patient's chest pain, which may have subsided hours earlier, is related to heart disease or something else, such as indigestion. The results of the study appear today in Circulation Online and will appear in the print version of Circulation on October 4, 2005.
"We are excited about this agent because it extends the time window for identifying myocardial ischemia, a common cause of chest pain, long after the pain stops and blood flow to the heart returns to normal," says lead investigator Vasken Dilsizian, M.D., professor of medicine and diagnostic radiology and nuclear medicine at the University of Maryland School of Medicine and director of Cardiovascular Nuclear Medicine at the University of Maryland Medical Center. "This probe provides a direct connection to the cause of the chest pain without requiring a treadmill stress test or use of a drug that produces stress to assess heart function," says Dr. Dilsizian.
Nuclear medicine combines computers, detectors and radioactive substances called radioisotopes to produce images of blood flow and biochemical functions in the heart and other organs. The radioactive tracer evaluated for this study, known by the brand name Zemiva, links a fatty acid to a radioisotope which is injected in the patient. The researchers used a technique called SPECT (Single Photon Emission Computed Tomography) to evaluate the tracer in this study.
The heart normally uses fatty acid as its primary fuel source for energy. Decreased blood flow to the heart, caused either by narrowed or clogged arteries or increased demand on the heart during strenuous exercise, sets off a metabolic disturbance that slows down or halts the way fatty acid is normally utilized. The condition is called myocardial ischemia. The disturbance causes the heart to switch from fatty acid as its primary fuel to glucose. The new tracer test keys in on this metabolic disturbance and seemingly remembers the imprint of an episode of reduced blood flow long after the episode, a process that is called "ischemic memory." According to Dr. Dilsizian, "When you image the heart, you see lack of or reduced fatty acid metabolism."
Thirty-two patients from four centers were enrolled in the study. To determine the accuracy of images acquired by Zemiva, the researchers first identified patients who had evidence of myocardial ischemia on a treadmill using a standard tracer called thalium to produce SPECT images. Later, SPECT images of the same patients were taken with the new tracer (Zemiva) injected at rest (without repeating the treadmill exercise), but no more that 30 hours after the exercise thalium test. The exercise-induced thalium-based images were compared with the rest-injected Zimeva images. The comparison showed the two tracers pointed to the same abnormality in the heart in over 90 percent of the cases. This suggests that disturbances in fatty acid metabolism can persist up to 30 hours after an ischemic episode, which can be imaged with the new tracer Zemiva.
Additional testing will be required before this new agent can be approved by the U.S. Food and Drug Administration.
The research team also included Timothy M. Bateman, M.D., Cardiovascular Consultants, Kansas City, MO; Steven R. Bergmann, M.D., Ph.D., College of Physicans and Surgeons of Columbia University; Roger Des Prez, M.D., Oklahoma Heart Institute; Martin Y. Magram, M.D., University of Maryland Medical Center and the University of Maryland School of Medicine; Anne E. Goodbody, Ph.D., and John W. Babich, Ph.D., Molecular Insight Pharmaceuticals, and James E. Udelson, M.D., Tufts-New England Medical Center and Tufts Univeristy School of Medicine. The study was funded by Molecular Insight Pharmaceuticals, maker of Zemiva.
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