April 2, 2009 (Orlando, Florida) — Myocardial scintigraphy, a simple nuclear imaging test that evaluates the integrity of the sympathetic nerves supplying the heart, can identify which heart-failure patients are more likely to have a worse prognosis, according to the results of the ADMIRE-HF trial.
Presenting the trial at the American College of Cardiology (ACC) 2009 Scientific Sessions, Dr Arnold Jacobson (GE Healthcare) said, "It's been known for a long time that the sympathetic nerves are damaged in heart failure, and this test allows better discrimination of the level of risk, identifying in particular those at very high risk, where additional protective therapy might be best used. It also identifies well those at much lower risk who will do very well."
The test, which has the brand name AdreView, uses the radioactive tracer 123I meta-iodobenzylguanidine (123I mIBG), which is a physiologic analog of norepinephrine and is taken up into sympathetic nerves. Jacobson explained that the sympathetic nervous system is less active in heart failure, and studies in Japan and Europe have suggested that lower uptake of 123I mIBG is associated with poorer outcomes. But these studies have generally been single center, with no standardization of uptake analysis methodology and diagnostic criteria, and end points were not always prospectively established. ADMIRE-HF was therefore conducted to be a more definitive trial.
In the trial, 964 patients with class 2 and 3 heart failure were given 123I mIBG by IV injection and underwent nuclear imaging. Quantification of cardiac uptake of the tracer was expressed as the ratio of counts between the heart and the upper mediastinum--the H/M ratio. Jacobson noted that normal healthy individuals would have an H/M ratio of around 2 and that in the sickest heart failure this would be reduced to about 1. For the purposes of this study, a cutoff value of 1.6 was used, with values higher than this denoting high uptake and values below this denoting low uptake.
Patients were followed for a maximum of two years. Results showed that the composite end point, the first occurrence of NYHA heart-failure class progression, potentially life-threatening arrhythmic event, or cardiac death, as determined by an independent adjudication panel, occurred significantly more frequently in patients who had low uptake of the tracer.
ADMIRE–HF Primary End Point
|End point||Low uptake (%)||Higher uptake (%)||p|
|CHF progression, life-threatening arrhythmia, or cardiac death||37||15||0.0001|
Jacobson also reported that there were 51 cardiac deaths in the low-uptake group and just two in the higher-uptake group, and the negative predictive value of a high uptake for cardiac death over two years was 98.8%.
He added that the test was particularly effective in identifying those with the worst prognosis, with the group who were in the lowest 10% for uptake having a death rate 10 times those in the highest 20%.
Incidence of Death in Lowest 10% vs Highest 20% Uptake Groups
|Lowest 10% for uptake (%)||Highest 20% for uptake (%)|
He also showed data suggesting that this test had independent prognostic capability complementary to other commonly used markers such as LVEF and B-type natriuretic peptide (BNP) and that it might be able to discriminate between patients who were likely to die from heart-failure progression and those who would have an arrhythmic event. "Those with the lowest uptakes (H/M ratio <1.2) tended to die more from heart-failure progression, whereas arrhythmic events tended to occur in patients with H/M ratios in the 1.2-to-1.6 range," he said.
Jacobson concluded: "The use of the imaging test is consistent with the current trend toward gaining better and earlier understanding of heart disease at a molecular level in order to institute more effective prevention and management strategies. We’ve known about this testing method for years, but ADMIRE-HF is the first large-scale multicenter prospective validation of its prognostic power and provides data that clinicians may be able to use to improve current practice."
Could It Be Used to Guide Defibrillator Use?
Chair of an ACC press conference at which this study was highlighted, Dr Aaron Kugelmass (Heart and Vascular Center, Springfield, MA), asked whether this sort of test might be able to help build up a picture of which heart-failure patients would benefit most from a defibrillator. "We would like to figure this out in a more finely tuned way than we do at the moment," he commented. Jacobson suggested that that might be a possibility, pointing out that in the 20% of patients with more normal cardiac uptake the cardiac death rate was very low--less than 1% per year.
The study was funded by GE Healthcare, where Jacobson is an employee.
Heartwire from Medscape © 2009 Medscape, LLC
Cite this: ACC 2009: ADMIRE-HF: New Imaging Test Helps Better Define Risk in Heart Failure - Medscape - Apr 02, 2009.