The Combined Prognostic Potential of Serum High‐Sensitivity Cardiac Troponin I and N‐Terminal pro‐B‐Type Natriuretic Peptide Concentrations in Dogs with Degenerative Mitral Valve Disease

Abstract

Background: Identification of factors associated with decreased survival in dogs with degenerative mitral valve disease (DMVD) will allow more accurate prognosis. N-terminal pro-B-type natriuretic peptide (NT-proBNP) is negatively associated with survival in dogs with DMVD. In human patients, multimarker strategies provide superior risk stratification compared with single markers.Hypothesis: High-sensitivity cardiac troponin I (hscTnI) and other clinical variables will be associated with survival time in dogs with DMVD. Measuring hscTnI and NT-proBNP in combination will be prognostically superior to measurement of either marker alone. The rate of change of these markers will vary according to cause of death.Animals: Client-owned dogs (n = 202) with DMVD of varying severity and age-matched healthy control dogs (n = 30) recruited from first opinion private practice.Methods: Prospective cohort study relating clinical variables at enrollment in dogs with DMVD to survival time (allcause, cardiac, and noncardiac mortality). Multivariable Cox regression analysis was used to identify factors associated with survival. Measurements were obtained approximately every 6 months. Repeated measures models were constructed to assess changes over time.Results: hscTnI, LVEDDN, heart rate, and age were independently associated with decreased survival time (all-cause mortality). Survival times were shortest in dogs in which both serum hscTnI and NT-proBNP were increased. hscTnI and NT-proBNP increased more rapidly in dogs that died of cardiac disease.Conclusions and Clinical Importance: Serum hscTnI has prognostic value in dogs with DMVD. Measurement of NTproBNP and hscTnI is prognostically superior to measuring either alone. Serial measurement strategies provide additional prognostic information.

Degenerative mitral valve disease: Survival of dogs attending primary-care practice in England

“…In agreement with a previous study (Hezzell et al, 2012), there was strong evidence for an 312 association between age and all-cause mortality in dogs with DMVD, with hazard of death 313 increasing 3.85 fold (95% CI: 2.61 -5.69) for each 5 year increase in age at diagnosis. In 314 addition to being an independent predictor of outcome, age at diagnosis confounded the 315 associations between breed and hazard of death, highlighting the importance of multivariable 316 analyses when interpreting the effect of explanatory variables in epidemiological studies.…”

Analytical validation of a second-generation immunoassay for the quantification of N-terminal pro–B-type natriuretic peptide in canine blood

“…1,10 In addition, studies have shown that the presence of elevated levels of NT-proBNP may be an indicator to assist in predicting the first onset of congestive heart failure in dogs with mitral valve disease as well as prognostic information on survival. 8,9,11,12,17 A first-generation immunoassay for the quantitative measurement of NT-proBNP in canine plasma a provided reproducible results from ethylenediamine tetra-acetic acid (EDTA) plasma samples in a range of 50-3000 pmol/l with coefficients of variation (CVs) for intra-and interassay precision of <15% across the full range of the assay. 1,14 The enzyme-linked immunosorbent assay (ELISA) utilized 2 affinity-purified sheep anti-canine NT-proBNP polyclonal antibodies, one on the solid phase capture and another in the liquid detection reagent.…”

Breed Differences in Natriuretic Peptides in Healthy Dogs

“…Increased plasma NP concentrations have been identified in dogs with dilated cardiomyopathy (DCM) 2, 3, 4, 5, 6, 7. Furthermore, NP concentrations have been shown to increase with increasing disease severity in dogs with myxomatous mitral valve disease (MMVD),3, 8, 9, 10, 11 and NT‐proBNP has been suggested to be predictive of outcome in dogs with MMVD 9, 12, 13, 14, 15, 16. Natriuretic peptides also have been found useful to distinguish CHF from respiratory disease 12, 17, 18, 19, 20.…”