Untargeted metabolomic profiling of dogs with myxomatous mitral valve disease and congestive heart failure shows metabolic differences associated with the presence of cardiac cachexia

Objective: To determine the effects of cardiac cachexia on the metabolomic profile in dogs with myxomatous mitral valve disease (MMVD).

Animals: 3 groups of dogs with MMVD enrolled between November 30, 2018, and April 7, 2022: (1) Dogs with congestive heart failure (CHF) and cachexia (CHF-cachexia group; n = 10); (2) dogs with CHF that had no cachexia (CHF-no cachexia group; n = 10); and (3) dogs with asymptomatic disease (American College of Veterinary Internal Medicine [ACVIM] Stage B2) with no cachexia (B2 group; n = 10).

Methods: Metabolomic profiles were analyzed from serum samples using ultra-high-performance liquid chromatography-tandem mass spectroscopy. Dogs in the 3 groups were compared, with statistical significance defined as P < .05 with a low false discovery rate (q < .10) and nominal statistical significance defined as P < .05 but q > .10.

Results: Numerous metabolites were significantly (n = 201) or nominally significantly (n = 345) different between groups. For example, when comparing the CHF-cachexia vs CHF-no cachexia groups, lipids were the predominant metabolite differences, including many medium- and long-chain dicarboxylates and dicarboxylate acylcarnitines. For comparisons of the CHF-cachexia vs B2 groups and the CHF-no cachexia vs B2 groups, amino acids, nucleotides, and cofactors/vitamins were the predominant metabolite differences.

Clinical relevance: Some significant metabolite differences were identified between dogs with and without cardiac cachexia.