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Angelika Hammerer-Lercher, et al. Are Heart Failure Management Recommendations and Guidelines Followed in Laboratory Medicine in Europe and North America? The Cardiac Marker Guideline Uptake in Europe (CARMAGUE) Study. J Appl Lab Med 2017;1:460-461.
Dr. Angelika Hammerer-Lercher is Deputy Director of Institute for Laboratory Medicine at the Kantonsspital Aarau, Switzerland.
Hello, and welcome to this edition of “JALM Talk” from The Journal of Applied Laboratory Medicine, a publication of the American Association for Clinical Chemistry. I’m your host, Randye Kaye.
Heart failure is a significant cause of decreased quality of life, morbidity, and mortality. Now currently, the most utilized biomarkers of heart failure are the natriuretic peptides, BNP and NT-proBNP. In 2012, the European Society of Cardiology, or ESC, released new guidelines regarding the appropriate cut-off concentrations of these biomarkers in ruling out acute and chronic heart failure. An article called, “Are Heart Failure Management Recommendations and Guidelines Followed in Laboratory Medicine in Europe and North America? The CARdiac MArker Guideline Uptake in Europe (CARMAGUE)” published in the March 2017 issue of JALM, commissioned a survey of laboratories in Europe and North America in order to investigate if labs were using the new ESC cut-off recommendations for BNP and NT-proBNP. Further, this survey sought to elucidate the reasons why labs measure one versus the other biomarker and whether the labs were accredited.
The first author of this article is Dr. Angelika Hammerer, Deputy Director of Institute for Laboratory Medicine at the Kantonsspital Aarau, Switzerland. She was a member of the recently concluded working group “Cardiac Markers” of the European Federation of Clinical Chemistry and Laboratory Medicine and she’s our guest for today’s podcast. Welcome, Dr. Hammerer.
First question, why is the natriuretic peptide testing so important?
Patients with acute heart failure show up with acute breathlessness and non-specific symptoms, so that the differential diagnosis is not always easy. Biomarkers like natriuretic peptides help to triage these patients.
Heart failure is a disease with a poor medium-term
prognosis and decreased quality of life. In patients with
acute heart failure the cumulative all-cause 1-year mortality
is as high as 17%. The American Heart Association
forecasted a 3-fold increase in costs within the next decade,
attributed to an aging population. On the other hand, good
therapies are available and medications have been
developed to improve the outcome. One of these is the
promising angiotensin receptor-neprilysin inhibitor,
How well-established is the measurement of natriuretic
peptides for the differential diagnosis of breathlessness like
in heart failure?
Our survey showed that laboratories offering natriuretic
peptide testing did not increase between 2009 and 2013 and
stayed merely the same at around 6% to 7%. In North
American Laboratories only around 58% offer these assays.
We did not expect these rather low numbers particularly
after the incorporation of natriuretic peptide testing into the
guidelines over several years. However, most of the
laboratories provided the 24-hour laboratory service.
What do the guidelines say concerning cut-off values for
natriuretic peptides and are they used in the laboratories?
At the time of our survey, which was closed in August 2013,
the 2012 European Society of Cardiology guidelines as well
as the ESC recommendations had just been published and
the American College of Cardiology Foundation/American
Heart Association came out in 2013. The guidelines placed a
high value on echocardiography besides natriuretic peptide
testing. However, in the ACCF/AHA guidelines no explicit
natriuretic peptide cut-off values were stated in 2013.
The ESC guidelines of 2012 showed a different algorithm
than the ESC recommendations of the same year. Thus, in
the ESC guidelines, single cut-off values for ruling out acute
or chronic heart failure were recommended, which were
confirmed in the most recent ESC guidelines of last year
with a class I-A recommendation. What we have seen from
our survey is, that only around 5% of participant
laboratories measuring NT-proBNP followed the guidelines,
whereas for BNP this was better, with around half of
labororatories using the recommended 100 ng/L cut-off for
acute heart failure.
There were several (around 20%) laboratories using the
age-dependent rule-in cut-off values for NT-proBNP which
were part of the recommendations. It seems that the
publication of two different algorithm by the ESC in 2012
caused some confusion around which cut-off limits should be applied, particularly for NT-proBNP. We found a substantial
variability in decision limits used. Interestingly, there were a
few laboratories who did not know the cut-off values. We
hope that this situation improves within the near future.
I hope so too. How could this situation be improved?>/p>
Yeah, for a successful dissemination of guidelines,
practitioners should have the four A’s: awareness,
agreement, adoption, and adherence. To address awareness
and agreement, our working group for cardiac markers
sought cooperation with cardiology societies and held joint
sessions during symposia with clinical societies to educate
professionals, for example at EUROMEDLAB in Milano in
2013 or last year at the EFLM Congress in Warsaw.
Adaptation and adherence can be addressed in many ways,
including monitoring metrics established at individual
medical institutions. This will be part of these scientific
sessions and is also aided by our publications documenting
that evidence is not widely implemented, such as presented
here. And at best, written guidelines for heart failure workup
should be established jointly by laboratorians and
Okay, very interesting. Are there any confounding variables
to be considered when measuring natriuretic peptides?
Many heart failure patients show comorbidities, such as
impaired renal function, that cause high natriuretic peptide
values, because natriuretic peptides also regulate the saltwater
balance in the body. Therefore, cut-off values should
be higher in these patients. In contrast to the patients with
impaired renal function, in obese patients natriuretic peptide
values decline according to the increasing body mass index,
which means that cut-off values should be lower in these
However, the shifts in natriuretic peptides cut-off values for
renal failure and obesity have not yet been defined in the
new ESC guidelines. In addition, in patients treated with the
new neprilysin inhibiting drug Entresto, higher BNP and
lower NT-proBNP levels were reported several weeks after
treatment initiation. However, the proBNP system, with its
many circulating forms, is very complex and requires further
investigation to find the optimal type of natriuretic peptide
measurement for patient monitoring and maybe should
As around half of the survey participants offered natriuretic
peptide assays for serial in- or out-patient monitoring,
medication with neprilysin inhibitors will certainly be a
challenge for laboratorians and clinicians in measuring and understanding natriuretic peptide values post-therapy with
Very interesting. Thank you so much for joining us today.
That was Dr. Angelika Hammerer from the Institute for
Laboratory Medicine in Aarau, Switzerland talking about the
JALM article, “Are Heart Failure Management
Recommendations and Guidelines Followed in Laboratory
Medicine in Europe and North America? The CARdiac MArker
Guideline Uptake in Europe (CARMAGUE)” for this podcast.
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