NEW YORK — New agents and imaging methods will change the way that hearts are scanned in coming years, researchers said at the annual meeting of the American Society of Nuclear Cardiology.
Myocardial Hyperemia Drugs
Adenosine and dipyridamole are the current mainstays of pharmacologic stress during nuclear imaging, but both agents cause many adverse events, including atrioventricular block in up to 8% of patients and bronchospasm in a small but significant fraction. Bothersome adverse effects such as flushing, chest pain, and dyspnea occur in 50%‐80% of patients, said Robert C. Hendel, M.D., Rush University Medical Center in Chicago.
These features sparked an interest in developing more specific agonists for the A2A receptor that is responsible for coronary vasodilation. These agents have a reduced affinity for the A1, A2B, and A3 receptors that are the source of the adverse effects caused by adenosine and dipyridamole. Two new drugs are now in phase III trials: binodenoson, developed by King Pharmaceuticals Inc., and regadenoson, developed by CV Therapeutics Inc. A third agent, BMS068645, developed by Bristol‐Myers Squibb Co., is in phase II clinical studies.
Results from a phase II study with binodenoson that involved 203 patients showed that the new drug had “very good concordance with adenosine” for myocardial perfusion but with a “clear decrease in the overall adverse event profile,” Dr. Hendel said. In this study, adenosine triggered a 92% rate of adverse effects, compared with a 33%‐80% rate among patients treated with binodenoson, depending on the dosage. At a dosage of 1.5 mcg/kg, the dosage being used in phase III studies, binodenoson produced no atrioventricular block and a “minimal” incidence of tachycardia in this small study, he said.
Regadenoson was tested in a crossover study with 36 patients, where it showed about an 85% concordance with the effect of adenosine on myocardial ischemia. A dosage of 400 mcg produced a 61% rate of adverse effects, compared with an 83% rate when adenosine was used.
It's too early to say anything about the relative safety and efficacy of these new drugs, compared with each other, Dr. Hendel added.
A radionuclide that's just entering clinical testing in the United States has the potential to open a new avenue of cardiac imaging by tagging regions of the myocardium that were ischemic hours earlier. Known as BMIPP, this radioiodine tracer is a fatty acid analogue that takes advantage of the disturbed fatty acid metabolism that persists in tissues for a relatively prolonged period following ischemia, said James E. Udelson, M.D., director of the nuclear cardiology laboratory at Tufts‐New England Medical Center in Boston. BMIPP has been used for several years in Japan.
The results from initial clinical studies in the United States have confirmed that BMIPP can selectively tag myocardium that has had ischemic stress more than 24 hours previously. “This agent may extend the time window for imaging ischemia beyond what we can do with a perfusion image,” he said.
One especially attractive prospect is to use BMIPP simultaneously with a standard radionuclide marker of myocardial perfusion such as thallium‐201 or technetium‐99m sestamibi. This would allow physicians to get information on both metabolic ischemia and resting perfusion “in one spin of the camera,” Dr. Udelson said.
Imaging the heart using a nuclear‐tagged norepinephrine analogue, metaiodobenzylguanidine (MIBG), allows researchers to assess myocardial innervation and the abnormal denervation that's associated with pathology (see above). Pilot studies show that MIBG imaging can give new insights into both primary and secondary cardioneuropathies, said Mark I. Travin, M.D., a cardiologist at Montefiore Medical Center in New York. Cardiac imaging with MIBG can identify dysautonomias and may allow early detection and definitive diagnosis of Parkinson's disease. MIBG abnormalities also occur in patients with idiopathic ventricular tachycardia and fibrillation. MIBG imaging may be a way to identify patients who are at high risk for sudden cardiac death and are the best candidates for receiving an implantable cardioverter defibrillator. MIBG imaging can also follow the progress of cardiac transplants.
The most important potential use for MIBG may be to assess coronary artery disease and heart failure. Neuronal imaging may detect the early stages of coronary disease before it becomes clinically apparent, Dr. Travin said. Patients with congestive heart failure usually have MIBG‐uptake abnormalities. This imaging may help guide therapy and provide a new way to assess efficacy.
The bottom images show vertical long‐axis views of a patient's heart labeled with 99mTc‐sestamibi, at rest, showing that coronary perfusion and viability were preserved in this region. The top images are from the same view of the heart, taken simultaneously with 123I‐MIBG. The low uptake of 123I‐MIBG on the inferior wall, in a region with good perfusion and viability, indicates sympathetic denervation. Courtesy Dr. Mark Travin