Significance
Cardiomyopathies affect both cats and humans, and they can cause serious consequence such as congestive heart failure (CHF). To date, the pathophysiological mechanism of CHF is not fully understood. In this study, for the first time, we used a proteomic approach combined with bioinformatic analysis to evaluate serum protein change in cats with CHF. Results indicate systemic inflammation, coagulation protein changes, innate immunity and extracellular matrix remodeling are involved in feline CHF, which are largely comparable with findings in previous human studies. Our study provides new insights into CHF and cardiomyopathy in cats, and the identified novel biomarkers and pathophysiological pathways provide valuable information for future studies.