Bullish Forecast for Natriuretic Peptide Testing

July 18, 2012

July 18, 2012 (San Diego, California) — Faith in the natriuretic peptide assay is nearly universal in the setting of acute heart failure, in that measurements of B-type natriuretic peptide (BNP) or N-terminal pro-BNP (NTproBNP) levels are an accepted part of the differential diagnosis. Yet there is abundant evidence supporting a range of other uses for assays that clinical practice will accept more slowly over the coming years.

So observes a state-of-the-art article [1] highlighting the use of natriuretic peptide assays in the decade since publication of the seminal Breathing Not Properly (BNP) trial, which ushered in their flagship application in the emergency department.

"In just 10 years, BNP has gone from being an unknown biomarker to one of the most useful in cardiology and beyond," write Drs Alan S Maisel and Lori B Daniels (University of California, San Diego) in their report, which kicks off a special Journal of the American College of Cardiology focus issue on biomarkers.

A central component of the article--a graphic that compares the current confidence of clinicians in natriuretic peptide assays vs their projected level of acceptance over the next five years--shows the authors' take on how their use may grow in the near future.

The graphic suggests that for several uses other than acute heart failure diagnosis, current acceptance is low although projected acceptance is high. They tend to be applications for which there is currently burgeoning evidence that has yet to be assimilated into practice, coauthor Daniels explained to heartwire . Those uses include following patients' status while hospitalized, risk prediction from in-hospital assay results, guiding treatment decisions in heart failure outpatients, screening for subclinical LV dysfunction (probably in selected populations), and as a contributor to the diagnosis of heart failure with preserved ejection fraction (HFPEF).

Some early studies of natriuretic-peptide guidance of outpatient therapy showed the strategy improved outcomes, others did not, Daniels observed. When it works, it can help fine-tune the dosing of diuretics and other drugs in individual patients. "Recently, there have been more and more studies showing that it can improve outcomes, so that's a growing area for sure."

The potential application shown in the graphic with arguably the greatest disparity between "current and future acceptance" of natriuretic peptide assays is in the diagnosis of HFPEF. The evidence base favoring such a use of the assays is fairly strong, but it's a hard sell for many clinicians.

"When there is HFPEF without [measuring] natriuretic peptides, you're relying on a completely clinical diagnosis that you have confidence in," Daniels said. "Then you do the ultrasound and you see essentially a normal looking heart, with normal systolic function," and the diagnosis becomes less certain while concern that the clinical signs are caused by something besides heart failure goes up.

"That's why it's an area in which we believe natriuretic peptides are quite important," she said. Without them, "it's an area in which one truly can make a misdiagnosis."

According to the article, another likely growth area for natriuretic peptides is as a component of multimarker panels. For this particular use--"a very hot research area," Daniels said--"the hope is that [the multimarker panels] can help in diagnosis and prognosis, and actually maybe get at the etiology of some of these disease processes" that can cause heart failure.

Candidate biomarkers besides natriuretic peptides are under exploration, "but we don't yet know what to do with the information," she said. Most biomarkers that are likely to end up in multimarker panels will probably have specific targets, but "it's pretty phenomenal how broadly useful natriuretic peptides are, showing utility across a wide range of pathologies."

The report was partly supported by a grant to Daniels from the American Heart Association; Daniels further discloses receiving research grants from Alere and Roche Diagnostics, and consulting for Alere. Maisel discloses receiving research grants from Abbott Diagnostics, Brahms USA, Alere, and Roche Diagnostics, and consulting for Alere and Critical Diagnostics. All mentioned companies have or are developing assays for natriuretic peptides or other biomarkers.

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