Evaluation of new and old biomarkers in dogs with degenerative mitral valve disease

Abstract

Background Dogs with degenerative mitral valve disease are commonly presented to small animal clinicians. Diagnosis, clinical staging, and therapeutic design are based on a combination of clinical examination, radiography, and echocardiography. To support diagnosis and clinical monitoring, a multi-marker-based approach would be conceivable. The aim of this study was to investigate the suitability of Galectin-3 and interleukin-1 receptor-like 1 protein (ST2) in dogs with degenerative mitral valve disease in accordance with N-terminal-prohormone-B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI). For this purpose, serum concentrations of Galectin-3 and ST2 of 64 dogs with different stages of mitral valve disease and 21 dogs without cardiac disease were analyzed at the first examination and six months later. Echocardiography, blood cell count and clinical chemistry were performed and established biomarkers NT-proBNP and cTnI were measured additionally. Differences in the biomarker concentrations between all groups at both timepoints and the change in biomarker concentrations from first to second evaluation was investigated. Furthermore, correlations of each biomarker, between biomarkers and echocardiographic measurements, were calculated. Finally, the receiver-operating characteristic curve and the area under the curve analysis were performed to differentiate between disease stages and controls. Results Serum concentrations of Galectin-3 and ST2 were not statistically different between canine patients in the respective stages of mitral valve disease or in comparison to dogs in the control group at any timepoint. A significant increase in ST2 concentrations from the baseline to the follow-up examination was observed in dogs classified as stage B1 and the control group. The concentrations of NT-proBNP and cTnI in stage C dogs were significantly increased in comparison to the other groups. Conclusions In this study, no relation between Galectin-3 and ST2 levels to the presence or stage of mitral valve disease could be detected. Nevertheless, considering the increase in ST2 concentrations from the first to second measurement, its value on monitoring disease progress could be feasible. In agreement with previous studies, NT-proBNP and cTnI have once more proven their utility in assessing disease severity. The approach of examining new cardiac biomarkers in dogs is still worth pursuing.

Serum Proteomic Profiles Reflect the Stages of Myxomatous Mitral Valve Disease in Dogs

“…Although ST2 proved to be an unspecific marker, recent studies on myxomatous degeneration suggest that the cytokine interleukin-33/ST2 pathway may be amplifying extracellular matrix remodeling in mitral valves [ 27 ]. Unfortunately, studies investigating circulating ST2 concentrations in canine MMVD [ 17 , 28 ], including our study, have, up to now, not been successful in showing significant differences between healthy and diseased states. Further research is needed before definitive conclusions.…”

“…The cTnI and NT-ProBNP were implemented for detection of myocardial injury and ventricular wall stress in dogs. A study by Kuleš et al showed higher serum concentrations of these two markers in dogs diagnosed with MMVD stage C compared to healthy dogs [ 9 ] and other MMVD stages [ 17 ]. Since echocardiography and radiography (the gold diagnostic standards for canine MMVD) and veterinary cardiologists are primarily situated in larger clinics, this, as well as increased costs of examination, limit the access for some dog owners.…”

The role of visual diagnostics in establishing the stages of development of mitral valve insufficiency in dogs

“…The choice of diagnostic test for heart disease in dogs is an important stage in the examination of the animal [4][5][6][7]. One of the most accessible and informative methods is echocardiography, which allows one to evaluate the structures of the heart, such as the valve apparatus, heart chambers and great vessels [7][8][9][10][11]. In this regard, the purpose of the study is to evaluate the role of visual diagnostics in establishing the stages of development of mitral valve insufficiency in dogs.…”

Proteomic analysis of the serum in dogs with pulmonary hypertension secondary to myxomatous mitral valve disease: the preliminary study

“…Biomarker measurement is of interest as a possible alternative method for early detection of various diseases ( 12 ). N-terminal pro B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) have become significant in the veterinary cardiovascular field ( 13 ). However, these proteins are mainly used as additional diagnostic tools for MMVD ( 14 ) and are insufficient as biomarkers to detect PH in dogs ( 15–17 ).…”