Another biomarker in the natriuretic peptide family may be in the
offing for helping with the emergency-department diagnosis of acute
heart failure. A prospective study has concluded that, in that
setting, an assay for the mid-regional fragment of atrial
natriuretic peptide (ANP) prohormone (MR-proANP) is noninferior to
the well-established test for B-type natriuretic peptide (BNP) [1].

Moreover, the newer test appears to add independent information to
what is available from the currently used assays for BNP and the
comparable N-terminal BNP prohormone (NT-proBNP) in some patient
subgroups, for whom the latter tests are less conclusive, concluded
researchers at the European Society of Cardiology Congress 2008.

"The story's not closed on BNP and NT-proBNP as the only two
diagnostic markers that should be used for heart failure," Dr Alan S
Maisel (University of California, San Diego) told heartwire.

The instability of ANP itself makes it unsuitable as a diagnostic
marker, he said. "We've all known for years that ANP goes up in the
blood in heart failure, but you just couldn't measure it. The cool
thing about this prohormone fragment is that it has a correlation
with ANP activity in vivo and ex vivo and is very stable. . . . This
marker works just as well as the other peptides and may be
complementary because in some cases the others don't work as well."

One of the findings from the Biomarkers in Acute Heart Failure
(BACH) trial, which Maisel reported here, is that MR-proANP may add
to the diagnostic power of BNP and NT-proBNP in patients with mid-
range levels of those two peptides, which, he said, can be difficult
to interpret. Such "gray-area" patients, he said, can make up more
than a third of the dyspnea patients evaluated in the emergency
department. The addition of MR-proANP testing to the evaluation
would cut the size of that that group by about 30%, Maisel said.

A similar added benefit was seen in other types of dyspneic patients
who are hard to pin down with BNP and NT-proBNP, he said. These
included the very elderly, the obese, and those with renal
dysfunction.

All that suggests that a test for multiple peptides would be more
accurate than any single-marker test, according to Maisel. "We
haven't done this, but it's possible that some [group] could put
together [a test] for a couple of these neurohormones; then we could
really tease out the gray-area patients for whom BNP doesn't work
well," he said.

"I think this study is very much in vogue with the multimarker
approach that's emerging for the diagnosis of heart failure and
acute coronary syndromes, and I think it leaves us with some
questions to answer going on from here," said discussant Dr Theresa
A McDonagh (Royal Brompton & Harefield NHS Trust, London, UK) after
Maisel presented the BACH trial.

"What we do know about natriuretic peptides in the emergency-room
setting from three randomized, controlled studies is that they seem
to reduce costs in terms of length of stay, lower readmission rates,
and reduced time to discharge," she said. Now that MR-proANP has
been shown to be "equivalent" to BNP and NT-proBNP, "What would be
the extra cost of adding MR-proANP to BNP in the emergency-room
setting, and would that additional cost justify these modest gains
in diagnostic benefit?" Also, she asked, "Will it predict prognosis
as well as BNP in acute heart failure?"

Maisel said to heartwire that another BACH analysis, to be presented
at a future meeting, is comparing the prognostic capabilities of MR-
proANP and BNP in the trial.

BACH entered 1636 patients evaluated in the emergency department for
dyspnea without an obvious cause at 15 centers in the US, Europe,
and New Zealand, of whom 567 received a final diagnosis of heart
failure.

Results for the two tests were highly correlated (r=0.919, p<0.001);
positive test results were defined as >120 pmol/L for MR-proANP and
>100 pg/mL for BNP. Using those cut points, the two tests were
comparable--well within the 10% difference that was the prespecified
limit for noninferiority, Maisel noted--with respect to sensitivity,
specificity, and diagnostic accuracy for acute heart failure.

In a secondary analysis, both markers were independently predictive
of heart failure. "When you control for MR-proANP, BNP does add
complementary information. And vice versa--if you control for BNP,
you can still get a lot of diagnostic information from MR-proANP,"
Maisel said in his presentation.

MR-proANP was significantly more diagnostic than BNP and NT-proBNP
in patients with the mid-range readings for the latter peptides and
a few patient subgroups. For example, it was more diagnostic than
BNP in obese patients (p=0.019) and in those with BNP readings >100
to <500 pmol/mL (p=0.002). And it was more diagnostic than NT-proBNP
in patients with readings for that peptide of >30 to <900 (p=0.005)
and in those with elevated creatinine (p<0.001), the obese
(p=0.001), and those 70 years or older (p=0.001) or with edema
(p=0.002).

The investigational MR-proANP diagnostic test is made by Brahms
Diagnostics; the test for BNP is available from Biosite; and tests
for NT-proBNP are available from Roche Diagnostics and bioMérieux.

Maisel disclosed that he has received research support from Brahms
Diagnostics, Roche Diagnostics, Abbott Healthcare, Biosite, and
Siemens.

Maisel AS. Results from the BACH (Biomarkers in Acute Heart Failure)
Trial. European Society of Cardiology Congress 2008; September 2,
2008; Munich, Germany. Clinical trials update 2.