Page 76 - Feline Cardiology

72 Section B: Diagnostic Testing

with mild HCM may have normal cTnI levels, several a cost-effective way (Maisel et al. 2006). Mature ANP
studies have shown that cats with moderate to severe and BNP have short half-lives, so most clinical assays
HCM have significantly higher levels of circulating cTnI target prohormones (NT-proANP and NT-proBNP),
than normal cats (Herndon et al. 2002; Connolly et al. which are more stable. Depending on the assay being
2003), and a weak correlation exists between cTnI con- used, heparinized or EDTA plasma or serum is submit-
Diagnostic Testing several studies have shown that plasma cTnI levels may centrifuged and separated after collection. If analysis is
centrations and ventricular wall thickness. More recently,
ted to the appropriate laboratory. Samples should be
be clinically useful for differentiating cardiac from non-
delayed more than a day, samples should be frozen. The
natriuretic peptides are cleared by the kidneys.
cardiac causes of dyspnea (Herndon et al. 2008; Connolly
et al. 2009; Wells [in press]). Now that several cage-side,
Hypervolemia and hypertension (characteristic of renal
point-of-care tests are available, cTnI testing should
prove useful for rapid triage of cats presenting with failure) enhance its secretion and elevate the levels of
BNP (because of increased ventricular pressure), espe-
severe dyspnea. cially NT-pro-BNP. In humans, there is also a moderate
Elevated cTnI levels have also been recognized in increase in the level of circulating BNP with increasing
groups of cats without hypertrophic cardiomyopathy. age. One must consider these possible confounding
Approximately 50% of hyperthyroid cats (without factors when interpreting the natriuretic peptide levels
underlying heart disease) in one study were found to in an individual patient.
have elevated baseline cTnI levels, which generally Several studies have evaluated the use of these bio-
returned to normal within 2 months of radioactive markers in feline heart disease patients. Plasma NT-
iodine therapy (Connolly et al. 2005). Although not proANP immunoreactivity was compared between two
reaching statistical significance, the cats with cTnI eleva- groups of cats with and without hypertrophic cardiomy-
tions also tended to have higher T 4 levels. The mecha- opathy, and no significant difference was found between
nism of troponin release was not determined although the two groups (MacLean et al. 2006). In this study, the
it was speculated to result from myocardial cell damage disease group was asymptomatic. In another study using
associated with intramural coronary ischemia or from an assay for C-terminal ANP, another group showed
the physiological effects of excess thyroid hormone. C-ANP levels increased from baseline in a model of
As of the writing of this chapter, two cTnI assays are feline volume overload, and C-ANP concentration was
available as cage-side tests (Heska i-STAT® and Biosite also significantly higher in cats with various forms of
Triage Meter®). Both assays have reasonable lower limits cardiomyopathy compared to normal cats. Moreover,
of detection (i-STAT®: 0.00 ng/ml, according to the man- cats with CHF had significantly higher C-ANP levels
ufacturer; Triage Meter®: 0.05 ng/ml), and published ref- than did heart disease cats without CHF (Hori et al.
erence ranges for cats are available for both (see Box 8.1). 2008). Another study evaluated NT-proANP and NT-
proBNP in 28 healthy controls and 50 cats with heart
disease. The affected group had various forms of heart
NATRIURETIC PEPTIDES (ATRIAL AND B-TYPE
NATRIURETIC PEPTIDE; ANP AND BNP) disease and was farther broken down into those with
and without congestive heart failure. Both natriuretic
ANP and BNP are produced by myocardial tissue in peptides were significantly different between the three
response to increased pressure and wall stress and there- groups, with cats in heart failure having the highest
fore are markers for cardiac dysfunction and heart levels. Although there was overlap of NT-proANP levels
failure. Pre-proBNP is processed intracellularly to between the three groups, there was no overlap of the
proBNP, which is secreted by the cell. ProBNP then NT-proBNP levels suggesting this marker is likely supe-
undergoes further processing to yield the active hormone rior (Connolly et al. 2008), although in all of these
(BNP) and an inactive fragment, NT-proBNP. The studies its elevation mirrored the presence and severity
pattern for ANP production is similar. The primary of congestive heart failure (which could be diagnosed
stimulus for ANP and BNP production is increased radiographically with shorter turnaround time). The
transmural pressure or sudden wall stretch of an atrium 7–10-day variability of circulating NT-proBNP in
[ANP] or ventricle [BNP]. However, sustained eleva- normal and cardiomyopathic cats was demonstrated to
tions are facilitated by increased protein synthesis, which be low and unlikely to confound its interpretation
switches from the atria to the ventricles. BNP is princi- (Reynolds et al. 2010). However, 23% of the affected cats
pally regulated by ventricular wall stress and pressure (3/13) had normal NT-proBNP values, which could
load (Connolly et al. 2008). BNP was the first biomarker have confounded interpretation of the assay. These three
to prove its value in diagnosis, prognostication, and cats were asymptomatic (Reynolds et al. 2010). NT-
screening of human congestive heart failure patients in proBNP has also been used in a clinical trial assessing