Download Cardiac Biomarkers, Cardiotoxicity, and Active Collaboration

Journal of the American College of Cardiology
Ó 2014 by the American College of Cardiology Foundation
Published by Elsevier Inc.
EDITORIAL COMMENT
Cardiac Biomarkers,
Cardiotoxicity, and
Active Collaboration
Is This the Final Frontier or
the Wave We Should Catch?*
Daniel J. Lenihan, MD
Nashville, Tennessee
The development of new “targeted” cancer therapy or investigation of new strategies for delivering previously established treatments for specific cancers is a major concern in
oncology. It is clear that minimizing the potential for
cardiac-related toxicity during cancer therapy is of significant interest, and establishing cardiac safety during chemotherapy is critical for the development of new therapeutics.
In addition, the concept of cardiac disease exacerbated by
or resulting from cancer therapy in survivors of cancer is
a major issue faced by patients and providers alike (1). Cardiac
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toxicity occurs more frequently than anticipated, largely
because of the success of cancer therapy, which allows
patients to live much longer; subsequently, this treatment
can result in chronic cardiac conditions (2,3). It is notable
that cardiotoxicity and cardiac disease in patients with cancer
are not exactly the same, so an improved understanding of
the semantics of this area of cardiology is necessary to
provide optimal patient care and ensure cardiac safety in the
most productive manner (4).
In this issue of the Journal, Ky et al. (5) present a careful
analysis of a host of plasma biomarkers obtained in a serial
fashion in patients who were undergoing chemotherapy for
breast cancer with several chemotherapeutics. Overall, cardiotoxicity (specifically new-onset left ventricular dysfunction) was predicted by a significant rise in high-sensitivity
troponin I (TnI) and myeloperoxidase (MPO) values
compared with baseline. Each marker was modestly
predictive by itself, but the combination allowed for a more
confident association with subsequent left ventricular
*Editorials published in the Journal of the American College of Cardiology reflect the
views of the authors and do not necessarily represent the views of JACC or the
American College of Cardiology.
From the Division of Cardiovascular Medicine, Vanderbilt University, Nashville,
Tennessee. Dr. Lenihan has served as a consultant for Roche, Onyx, and AstraZeneca;
and has received research support from Acorda Therapeutics.
Vol. 63, No. 8, 2014
ISSN 0735-1097/$36.00
http://dx.doi.org/10.1016/j.jacc.2013.10.060
dysfunction. Five other biomarkers were similarly measured,
including N-terminal pro–B-type natriuretic peptide, and
there were not clear patterns associated with the detection of
left ventricular dysfunction. These data are quite important
in the respect that a plasma biomarker can provide early
insight into those at risk for cardiac dysfunction and could
help define a more aggressive strategy for cardioprotection
while a patient undergoes life-saving chemotherapy.
There are also important limitations of this report, many
of which are acknowledged by the authors in their discussion. Obviously, a larger patient population would be helpful
and provide potentially stronger associations with biomarker
elevations and subsequent left ventricular dysfunction, but
a careful initial analysis has to be performed to commit
to future studies. There have been some initial data on highsensitivity TnI as a marker of cardiotoxicity, with a threshold
that is clinically measurable (6), but the timing of the
biomarker measurement and the absolute threshold for abnormality are not established and have not been studied well
enough to make a strong recommendation for the detection
of cardiotoxicity at this time. The data presented in this
report do not inform a practicing cardiologist or oncologist
when or how to measure TnI or MPO in a clinical manner
or what to do with a result that is considered abnormal. In
terms of biomarkers, this is absolutely a charge that the
cardiology world should strive to meet, because there is
a tsunami of biomarker studies to consider (7).
Possibly the most important concept that these data
suggest is that a highly sophisticated cardiology-based evaluation during chemotherapy can be critical to the early
detection and ultimately the prevention of heart failure in
a patient population at high risk for the development of heart
failure. Cardiology needs to be involved in these patients with
cancer to interpret subtle imaging findings but also to help
place the biomarker measurements in a proper clinical
context, help educate about cardiac risk factors, and optimally
modify those risk factors when appropriate. Only then will
we actually be able to truly prevent heart failure in a manner
that was recently shown in a multicenter trial using biomarkers as a guide (8,9). There is some evidence that use of
cardioprotective therapy (carvedilol or enalapril) in patients at
very high risk is beneficial (10); however, it would seem that
using biomarker elevations to indicate those at highest risk
for cardiotoxicity and guide therapy based on those values is
the most useful, cost-effective, and sophisticated approach.
The use of highly sophisticated and expensive imaging that is
subject to local availability and expertise is not a widely
applicable strategy to detect cardiotoxicity in the broadest
clinical manner.
It is quite apparent that the participation of cardiology
in the care of patients with cancer is absolutely needed (11)
and is certainly consistent with having the patient as the
focal point of the team provider approach that is believed to
be the future of medicine. The impact of cardiac disease
on patients with cancer is profound and could be mitigated
or prevented with careful cardiology input. Furthermore,
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JACC Vol. 63, No. 8, 2014
March 4, 2014:817–8
Lenihan
Biomarkers, Cardiotoxicity, and Collaboration
confirming cardiac safety during drug development, especially with the investigation of more potent and ubiquitous
molecular targets in anticancer therapy, by using cardiacrelated biomarkers in an understandable and reliable manner would be a major advance in the field. Additionally,
the opportunity for cardiologists to work closely with our
oncology colleagues in a collegial manner (12) allows us to
learn from and teach each other for the betterment of our
patients. It is this wave of collaboration that we should all
experience and from which we should benefit.
Reprint requests and correspondence: Dr. Daniel J. Lenihan,
Division of Cardiovascular Medicine, Vanderbilt University, 1215
21st Avenue South, Suite 5209, Nashville, Tennessee 37232.
E-mail: [email protected].
REFERENCES
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Incidence of heart failure or cardiomyopathy after adjuvant trastuzumab
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Key Words: cardio-oncology
trastuzumab cardiotoxicity.
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chemotherapy cardiotoxicity
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