CHAPTER 47 Biochemical Tests for Cardiac Injury
Biomarkers for cardiac injury have become important diagnostic and prognostic tools in human medicine for several ischemic, toxic, and traumatic conditions of the heart. Historically, potential biochemical markers of cardiac muscle injury have included lactate dehydrogenase, the myocardial isoform of creatine kinase (CKMB), and cardiac troponins I (cTnI), T (cTnT), and C. Determination of the usefulness of assays for these markers in veterinary medicine is in its infancy, but a few case reports have been published in which cTnI was evaluated as a potential marker of acute cardiac injury in horses with spontaneous cardiac disease. Furthermore, two prospective studies have established reference guidelines for cTnI concentrations in racing Thoroughbreds in training and in lay-up at pasture, and another study established reference values for cTnI, cTnT, and CKMB in healthy neonatal foals. The myocardial band isoform of CK has been used clinically in a limited fashion in adult horses with acute myocardial injury, such as that seen with ionophore toxicosis, but I am aware of no peer-reviewed publications validating the utility of this test or the specificity and sensitivity of human CKMB assays for use in the horse. Lactate dehydrogenase can be dismissed as a marker of cardiac injury in horses because of lack of specificity.
Of central relevance to the accuracy and therefore diagnostic value of cardiac biomarkers is the issue of test availability and precision. No assays are available at present that specifically measure equine troponins or the equine myocardial band isoform of creatine kinase. Studies published at present relied on use of human assays, and as a consequence readers must be cautious in comparing values among studies or even among clinical cases and the published literature. Clinicians measuring cardiac troponins, for example, should ensure that comparisons are made with reference ranges established by data obtained with the same methods used by their laboratory before making a judgment on whether concentrations are high. Fortunately, the three published prospective studies that established reference ranges for cTnI concentrations in healthy Thoroughbreds and foals were performed with similar chemiluminescent immunoassays that were developed to detect human cTnI using mouse monoclonal antibodies directed against human subunit proteins.
The recent cloning∗ and sequencing of equine cTnI enabled one of these assays to be confirmed as a sensitive test for the equine protein. Several of the individual case reports cited in the literature used different assays and methods, and direct comparison of values among these studies is inappropriate. Equipment used for point-of-care or bedside measurement of troponins in humans has not been validated in horses.
Serum concentrations of cTnI in blood samples from healthy horses have been evaluated in three studies. The study by Phillips and colleagues used the Dimension Heterogenous Immunoassay∗ on serum samples and established a reference range of 0 to 0.35 ng/mL in pastured and training Thoroughbreds. In the study from Australia conducted by Begg and colleagues, the ADVIA Centaur Assay† was used to analyze serum and plasma samples from Thoroughbreds in training; in that study, there were no samples in which cTnI concentration was above the lower limit of detection (0.15 ng/mL) of the assay. In serum from healthy neonatal foals, reference ranges were 0.01 to 0.51 ng/mL, 0.009 to 0.20 ng/mL, and 0.40 to 9.3 g/mL for cTnI, cTnT, and CKMB concentrations, respectively. In that study, the ACCESS Immunoassay‡ was used to measure cTnI, and the Elecsys 2010 Immunoassay§ was used to determine mass measurements for cTnT and CKMB.