Experimental Compound Reveals Metabolic Disturbances In The Heart

"We are excited about this agent because it extends the time windowfor identifying myocardial ischemia, a common cause of chest pain, longafter the pain stops and blood flow to the heart returns to normal,"says lead investigator Vasken Dilsizian, M.D., professor of medicineand diagnostic radiology and nuclear medicine at the University ofMaryland School of Medicine and director of Cardiovascular NuclearMedicine at the University of Maryland Medical Center. "This probeprovides a direct connection to the cause of the chest pain withoutrequiring a treadmill stress test or use of a drug that produces stressto assess heart function," says Dr. Dilsizian.

Nuclear medicine combines computers, detectors and radioactivesubstances called radioisotopes to produce images of blood flow andbiochemical functions in the heart and other organs. The radioactivetracer evaluated for this study, known by the brand name Zemiva, linksa fatty acid to a radioisotope which is injected in the patient. Theresearchers used a technique called SPECT (Single Photon EmissionComputed Tomography) to evaluate the tracer in this study.

The heart normally uses fatty acid as its primary fuel sourcefor energy. Decreased blood flow to the heart, caused either bynarrowed or clogged arteries or increased demand on the heart duringstrenuous exercise, sets off a metabolic disturbance that slows down orhalts the way fatty acid is normally utilized. The condition is calledmyocardial ischemia. The disturbance causes the heart to switch fromfatty acid as its primary fuel to glucose. The new tracer test keys inon this metabolic disturbance and seemingly remembers the imprint of anepisode of reduced blood flow long after the episode, a process that iscalled "ischemic memory." According to Dr. Dilsizian, "When you imagethe heart, you see lack of or reduced fatty acid metabolism."

Thirty-two patients from four centers were enrolled in thestudy. To determine the accuracy of images acquired by Zemiva, theresearchers first identified patients who had evidence of myocardialischemia on a treadmill using a standard tracer called thalium toproduce SPECT images. Later, SPECT images of the same patients weretaken with the new tracer (Zemiva) injected at rest (without repeatingthe treadmill exercise), but no more that 30 hours after the exercisethalium test. The exercise-induced thalium-based images were comparedwith the rest-injected Zimeva images. The comparison showed the twotracers pointed to the same abnormality in the heart in over 90 percentof the cases. This suggests that disturbances in fatty acid metabolismcan persist up to 30 hours after an ischemic episode, which can beimaged 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; RogerDes Prez, M.D., Oklahoma Heart Institute; Martin Y. Magram, M.D.,University of Maryland Medical Center and the University of MarylandSchool 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 ofMedicine. The study was funded by Molecular Insight Pharmaceuticals,maker of Zemiva.