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Chapter 8: Cardiac Biomarkers  73


              ramipril  therapy  in  asymptomatic  cats  with  HCM.  In   nostic  evaluation  (physical  examination,  echocardio-
              this study, ramipril did not change left ventricular mass   gram, etc.).
              or improve diastolic function (and similarly no signifi-  Clearance  of  natriuretic  peptides  in  mammals  is
              cant change was noted in NT-proBNP levels) (MacDonald   thought to occur renally. In cats with systemic hyperten-
              et al. 2006). A large-scale, single-institution, prospective   sion, since many have concurrent renal disease, interpre-
              study evaluating NT-proBNP levels in 425 cats covering   tation of NT-proBNP may be problematic. In a study
              the  full  clinical  spectrum  (normal  to  end-stage  heart   that  evaluated  natriuretic  peptides  in  cats  with  renal
              failure) has demonstrated serum NT-proBNP level cor-  disease,  only  NT-proANP  correlated  with  creatinine   Diagnostic Testing
              relates  with  stage  of  cardiovascular  disease  severity  as   concentrations, with NT-proBNP performing better as
              well as survival. This study also demonstrated that sex,   a diagnostic test. However, although azotemia was not a
              body weight, and blood pressure are not associated with   confounding  factor  in  the  evaluation  of  NT-proBNP,
              significant  differences  in  circulating  levels  of  NT-  systemic hypertension, as mentioned above, was associ-
              proBNP  (Ettinger  2010).  According  to  these  findings,   ated with an increase in NT-proBNP (Lalor et al. 2009).
              feline NT-proBNP levels below 100 pmol/l indicate that   Systemic hypertension likely stimulates increased pro-
              significant cardiovascular disease is unlikely, whereas a   duction of BNP secondary to elevated cardiac afterload.
              level greater than 270 pmol/l indicates clinically signifi-  Therefore, it is possible that elevated NT-proBNP levels
              cant disease is highly likely. NT-proBNP levels between   caused  by  systemic  hypertension  could  be  misinter-
              100–270 pmol/l  suggest  an  intermediate  result  where   preted as indicative of primary cardiomyopathy if blood
              cardiac  disease  can  neither  be  ruled  in  nor  ruled  out   pressure is not measured.
              (Ettinger 2010).                                     Several  human  studies  suggest  multiple  biomarker
                 At this time there is one assay for NT-proBNP on the   strategies are of greater value than using a single marker
              market  for  veterinary  use  in  the  United  States  (Idexx   alone.  It  is  likely  the  same  will  be  true  in  veterinary
              Cardiopet™ proBNP test) and the blood sample must   medicine.  The  search  for  new  biomarkers  for  human
              be  shipped  to  the  Idexx  laboratory  for  analysis.  Two   patients  is  ongoing,  and  studies  using  the  currently
              studies  focusing  on  clinical  relevancy  of  the  test  have   available ones will be essential to better define clinical
              shown that NT-proBNP can distinguish between con-  utility  for  these  tests.  The  rapid  development  of  this
              gestive  heart  failure  and  noncardiac  causes  of  acute   field seen to date will probably continue for the foresee-
              dyspnea in cats (Connolly et al. 2009; Fox et al. 2009).   able future. The possibility exists that these assays will
              See Table 8.1 for their suggested cutoff values. It is often   be  useful  for  prognosticating  and  optimizing  medical
              difficult to distinguish the underlying cause of dyspnea   management of individual feline cases. Until results are
              in  cats,  particularly  when  the  cat’s  severe  respiratory   rapidly available, they are unlikely to alter emergent care
              distress  limits  diagnostic  evaluation.  These  results   in  veterinary  medicine  and  there  is  currently  no  evi-
              suggest  NT-proBNP  levels  will  be  a  useful  adjunctive   dence they will be useful to screen asymptomatic cats
              diagnostic in these critically ill cats, especially when a   for underlying cardiomyopathy.
              rapid, cage-side test is available. However, the test was
              not useful for screening earlier stages of heart disease:   REFERENCES
              asymptomatic Maine coon or Maine coon crossbred cats
              with mild or moderate HCM did not have elevated NT   Boldface font indicates key references.
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                                                                   and cardiac troponin I. Clin Chem 1994;40:1291–1295.
              The test does not replace a traditional, complete diag-  Adin DB, Milner RJ, Berger KD, et al. Cardiac troponin I concnetra-
                                                                   tions in normal dogs and cats using a beside analyzer. J Vet Cardiol
                                                                   2005;7:27–32.
              Table 8.1.  Proposed	feline	circulating	plasma	NT-proBNP	cutoff	  Adin DB, Oyama MA, Sleeper MM, Milner RJ. Comparison of canine
              concentrations	for	discriminating	cats	with	dyspnea	caused	by	  cardiac troponin I concentrations as determined by 3 analyzers. J
                                                                   Vet Intern Med 2006;20:1136–1142.
              heart	disease	vs	respiratory	disease
                                                                 Apple FS. Clinical and analytical standardization issues confronting
                                                                   cardiac troponin I. Clin Chem 1999;45:18–20.
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                                                                 Bodor  GS,  Porterfield  D,  Voss  EM,  Smith  S,  Apple  FS.  Cardiac
                             proBNP	(pmol/l)  (%)    (%)
                                                                   troponin-I is not expressed in fetal and healthy or diseased adult
                                                                   human skeletal muscle tissue. Clin Chem 1995;41:1710–1715.
               Fox	et	al.	2009   265          90.2     87.9      Boswood A. Biomarkers in cardiovascular disease: Beyond natri-
               Connolly	et	al.	  220          93.9     87.8        uretic peptides. J of Vet Cardiol 2009;11:S23–S32.
               2009                                              Braunwald  E.  Biomarkers  in  heart  failure.  N  Engl  J  Med
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