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.

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%.

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. Weˇ¦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.