Page 75 - Feline Cardiology

Chapter 8: Cardiac Biomarkers 71

blood levels. This is followed by the slower release of
structurally bound troponin that results in a sustained Box 8.1. cTnI Reference Ranges for Normal Cats
elevation (Katus et al. 1991; Adams et al. 1994; Jaffe et
al. 1996). The half–life of cTnI and its complex in the Biosite Triage Meter® <0.05 ng/ml (95th percentile)
circulation is about two hours. The exact mechanism for Heska i-STAT® 0–0.17 ng/ml (median of 0.02 ng/ml)
elimination of cTnI is unknown but it is thought to
involve clearance by the reticuloendothelial system
(Freda cardiac TnI 2002). There is also some evidence Diagnostic Testing
that it may be broken down into small fragments that
could be excreted renally (Diris cardiac TnI 2004). Therefore, patients with mild elevations of cTnI could be
Elevated cardiac troponin levels indicate myocardial missed if using these assays. The higher sensitivity cardiac
damage but do not provide any information regarding troponin assays hold promise for addressing this problem
its cause. Cardiac troponins have emerged as sensitive (Reichlin 2009).
and specific markers of cardiomyocyte injury postmyo- Because of the many assays available for cTnI, there
cardial infarction, and elevations have been reported in has been some confusion regarding interpretation of
numerous canine studies secondary to myocarditis, results. Tests are not standardized, so manufacturers
blunt chest trauma, congestive heart failure, etc. Several may design them using proprietary antibodies that
feline studies have also shown the test may help identify target varying amino acid sequences on the cTnI mol-
patients affected with hypertrophic cardiomyopathy or ecule. In the bloodstream, cTnI can be modified or com-
hyperthyroidism (Herndon et al. 2002; Herndon et al. plexed to other proteins, such as cTnC, and the antibodies
2008; Connolly et al. 2003; Connolly et al. 2005). used in the assays may have differing specificity for each
However, results from three veterinary studies suggest circulating form of cTnI (Apple 1999; Katrukha et al.
there may be potential for prognostication or evaluation 1998). There exists no gold standard assay for cTnI at
of therapy response with cardiac troponin I (cTnI) this time. Comparison studies using a number of analyz-
(Oyama and Solter 2004; Côté 2007; Connolly et al. ers have concluded with the recommendation that, until
2005). assays are standardized, reference ranges should be
established for each individual assay. Therefore, absolute
Cardiac troponin assays values obtained from different assays cannot be com-
The currently available tests determine troponin levels by pared (Apple 1999; Panteghini et al. 2004; Adin et al.
using enzyme–linked immunosorbent assays (ELISA). 2006). Serum, heparinized plasma, or whole blood may
The difference in amino acid sequences from skeletal be sampled depending on which cTnI assay is used.
muscle and cardiac troponins (specifically TnI and T) has Studies in dogs have shown that cTnI levels do not sig-
allowed production of antibodies specific for cardiac nificantly change in serum stored at room temperature
troponins in these assays (Larue et al. 1992; Muller- over a 5-day period nor in serum that has undergone up
Bardorff et al. 1997). The first assays for detection of cTn to five freeze-thaw cycles (Schober et al. 2002; Oyama
were developed in the late 1980s. The tests have evolved and Solter 2004).
dramatically since their introduction, with greater sensi- Only one manufacturer produces an assay for cTnT,
tivity and improved precision. The turnaround time for which eliminates interassay comparison issues for cTnT.
results has also decreased from several hours to a few The first-generation cTnT assays used an antibody that
minutes. Point-of-care assays now exist that may be run cross-reacted with skeletal muscle troponin T, thereby
bedside or in the field, and reference ranges for cats have decreasing its specificity for cardiac injury (Katus et al.
been developed for at least two bedside analyzers (Adin 1992). Subsequent generations of cTnT assays have
et al. 2005; Wells [in press]). The first published cTnI refer- replaced this antibody with one that is more specific for
ence range for the feline species used the Dade Behring cTnT and thereby eliminated the false positives related
Stratus® with a range of <0.03–0.16 ng/ml (Sleeper et al. to skeletal muscle leakage (Muller-Bardorff et al. 1997).
2001). Currently there are at least two cTnI bedside ana- However, no published studies to date have evaluated
lyzers that have been validated in the feline species, the cTnT values in the feline species.
Biosite Triage Meter® and the Heska I-stat® handheld Hypertrophic cardiomyopathy (HCM), the most
analyzer with available cardiac troponin I cartridges. See common form of heart disease in cats, can cause intra-
Box 8.1 for normal feline values using these tests. When mural coronary artery disease, leading to microscopic
choosing an assay, it is important to consider the limit of areas of ischemia, and myocardial hypertrophy with cel-
detection. For some assays, the limit is 0.2 ng/ml, which lular necrosis and cTn release into the circulation
is actually outside the feline (and canine) normal range. (Maron et al. 1986; Krams et al. 1998). Although cats