Page 41 - Small Animal Internal Medicine, 6th Edition

CHAPTER 2
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Diagnostic Tests for the

Cardiovascular System

CARDIAC BIOCHEMICAL MARKERS can detect milder cTnI elevation in early to moderate cardiac
disease (such as with canine chronic mitral valve disease),
Certain cardiac biomarkers have potential diagnostic and although clinical utility remains to be defined.
prognostic utility in dogs and cats, especially the cardiac The natriuretic peptides (or their precursors) can be
troponins and natriuretic peptides. Cardiac troponins are useful biomarkers for identifying the presence and possibly
regulatory proteins attached to the cardiac actin (thin) con- prognosis of heart disease and CHF. Increased circulating
tractile filaments. Circulating concentrations of cardiac tro- concentrations occur with vascular volume expansion,
ponin proteins normally are very low; however, myocyte decreased renal clearance, and when their production is
injury allows their leakage into the cytoplasm and extracel- stimulated (as with atrial stretch, ventricular strain and
lular fluid. Cardiac troponin I (cTnI) is the protein usually hypertrophy, hypoxia, tachyarrhythmias, and occasionally
measured clinically. It is more sensitive for detecting myo- from ectopic noncardiac production). The natriuretic pep-
cardial injury than other biochemical markers of muscle tides (atrial [ANP] and brain [BNP]) help regulate blood
damage (such as cardiac-specific creatine kinase), although volume and pressure and antagonize the renin-angiotensin-
it usually does not differentiate the underlying cause. Serum aldosterone axis, among other effects. They are synthesized
cTnI increases relatively rapidly with severe injury. Because as preprohormones, then cleaved to a prohormone, and
the half-life of this biomarker is short, it can decrease rapidly; finally to their inactive amino terminal (NT-pro-) and active
the half-life in dogs has been estimated at about 6 hours. carboxyterminal (C-) fragments. The N-terminal fragments
Persistently increased cTnI indicates ongoing myocardial remain in circulation longer and reach higher plasma con-
damage. Moderate elevations in cTnI can occur in chronic centrations than the active hormone molecules.
heart disease, although levels often are normal with mild NT-proBNP is measured most often, and the degree of its
disease. This is thought to reflect myocardial remodeling. elevation generally correlates with cardiac disease severity.
Myocardial inflammation, trauma, various acquired and In animals with dyspnea, NT-proBNP measurement can
congenital cardiac diseases, and congestive heart failure help the clinician decide whether it is more likely due to CHF
(CHF) are associated with increased cTnI concentrations, or a noncardiac cause. Similar to cTnI, natriuretic peptides
although there can be overlap with clinically normal animals. are better used as functional markers of cardiac disease
Strenuous exercise and some noncardiac disease, such as rather than of specific pathology. However, circulating
gastric dilatation/volvulus, can be associated with minimal (NT-pro)BNP concentrations also can rise with certain
cTnI increases. Renal dysfunction can falsely elevate cTnI, noncardiac abnormalities, including renal dysfunction,
and older animals may have mildly elevated cTnI. Normal pulmonary hypertension, and hyperthyroidism (in cats).
Greyhounds appear to have slightly higher cTnI concentra- Species-specific assays are required. Canine and feline NT-
tion than other breeds. Human assays for cTnI can be used proBNP measurement is commercially available (Cardiopet
in dogs and cats. Standard (older) cTnI tests have a lower proBNP, Canine and Feline; IDEXX). Plasma concentrations
limit of detection of about 0.02 ng/mL with an upper detec- of less than (800-) 900 pmol/L (dogs) and less than
tion limit of about 40 ng/mL. Some labs consider a cTnI 100 pmol/L (cats) are associated with a low risk of clinically
concentration of 0.09 ng/mL as the upper limit of normal. significant heart disease. However, some Doberman Pin-
Others indicate that cTnI concentrations <0.2 ng/mL are to schers with occult cardiomyopathy have had NT-proBNP
be considered normal (Troponin I Canine/Feline, IDEXX). concentrations below this cut-off. Dogs with respiratory
A high-sensitivity cTnI test (with a detection range of signs, especially with a murmur, and a plasma NT-proBNP
0.006-50 ng/mL) has been validated in dogs and cats; this concentration >(1400-)1800 pmol/L are more likely to have

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