Evaluation of a sensitive cardiac troponin I assay as a screening test for the diagnosis of hypertrophic cardiomyopathy in cats.

Hertzsch S, Roos A, Wess G. Evaluation of a sensitive cardiac troponin I assay as a screening test for the diagnosis of hypertrophic cardiomyopathy in cats. J Vet Intern Med. 2019 Apr 16;. doi: 10.1111/jvim.15498.

Hypertrophic Cardiomyopathy (HCM) is the most common cause of cardiac disease in cats. It is caused by underlying genetic mutations and presents as a gradual thickening of the heart muscle associated with a decrease in the ability of the heart to fill with blood. The end stages of the disease may involve congestive heart failure (CHF), blood clots, or sudden death. A high percentage of cats with HCM have no clinical or physical exam findings until the onset of heart failure. The gold-standard test for HCM is the echocardiogram, which is a specialized procedure that may be costly and involve referral to a cardiologist, and as such is not often performed for screening asymptomatic cats. A blood test called nt-pro-BNP may be used to differentiate cats with respiratory distress due to heart disease from other causes, but has debatable utility as a screening test. Cardiac troponin I (cTnI) is commonly used to assess inflammation in the heart (ie heart attack, myocarditis), however recent data has suggested it may have utility as a screening test for HCM, especially in moderate to severe cases. The purpose of this study was to investigate a sensitive  cTnI assay as a screening test for HCM and determine the appropriate cut-off, and to determine if specific echocardiographic variables are associated with elevated cTnI.

The study was designed as a prospective observational study on client-owned cats presenting to a German veterinary hospital. Cats received a physical examination, basic bloodwork, blood pressure evaluation,  and echocardiography. They were excluded if they had a history of diseases known to cause left ventricular hypertrophy (ie hyperthyroidism, hypertension, renal disease, etc). HCM was diagnosed and classified into mild, moderate, or severe based on previously accepted criteria.

166 cats were included in the analysis (97 male, 69 female). 87 cats were classified as healthy, and 60 had HCM of some description (16 mild, 10 moderate, 34 severe). 14 cats were equivocal for HCM, and 4 presented with arterial thromboembolism.

Healthy cats were statistically significantly younger than cats with cardiac disease. Female cats were more likely to be healthy or have ATE, while male cats were more likely to have all other forms of cardiac disease.

The median cTnI concentration was significantly different between patient groups, with healthy and equivocal cats having significantly lower concentrations than other groups.  Cats with severe HCM had significantly higher concentrations than those with severe HCM, and cats with ATE had higher levels than mild or moderate. Healthy cats had a median cTnI of 0.013ng/mL, while those with ATE had a median of 6.413ng/mL.  Age, sex, and body weight did not have significant effects on cTnI concentrations.

Cats with HCM were further stratified into compensated, compensated under treatment, and decompensated groups, and it was found that those with compensated HCM had lower cTnI than decompensated or compensated under treatment.

Receiver Operating Characteristic (ROC) analysis was used to determine the ideal cut-off values for cTnI. A cut-off of 0.06ng/mL differentiated healthy cats from those with HCM with a sensitivity of 91.7% and specificity of 95.4%. This cut-off value also differentiated healthy cats from those with asymptomatic HCM with a sensitivity of 87.8% and specificity of 95.4%, and from those with severe HCM with a sensitivity of 100% and specificity of 95.4%. AUCROC values were 0.95, 0.93, and 0.99, respectively. Assuming a prevalence of 14.7% in the general population (from previous studies), the positive and negative predictive values differentiate healthy cats from cats with HCM were 77.4% and 98.5%, respectively, and for asymptomatic cats with HCM, 76.7% and 97.8%, respectively.

The authors conclude that a cut-off of 0.06ng/mL with a sensitive cTnI assay may be useful as a screening test for HCM in cats.

One limitation to this  study was the exclusion of cats with confounding issues. While understandable from the perspective of the study, many cats being screened for HCM may suffer from renal disease or other conditions, and the ability of the test to determine cardiac status in this population is important to determine. This study also used a highly sensitive cTnI assay, which may be able to detect more significant differences than the tests used in some laboratories.  It is also important to realize that elevated cTnI is not specific for HCM and may be found with myocarditis, cardiac ischemia, and likely other conditions as well.

Further work with larger populations, trending of values, and evaluation of effects of co-morbidities is important, however cTnI shows potential as a tool to screen cats for HCM.

See Also

Hori Y, Iguchi M, Heishima Y, et al. Diagnostic utility of cardiac troponin I in cats with hypertrophic cardiomyopathy. J Vet Intern Med. 2018;32:922-929.

Ferasin L, Sturgess CP, Cannon MJ, Caney SMA, Gruffydd-Jones TJ, Wotton PR. Feline idiopathic cardiomyopathy: a retrospective study of 106 cats (1994-2001). J Feline Med Surg. 2003;5:151-159.

Riesen SC, Kovacevic A, Lombard CW, Amberger C. Prevalence of heart disease in symptomatic cats: an overview from 1998 to 2005. Schweizer Archiv Tierheilkunde. 2007;149:65-71.