Phenotypic patterns in feline heart failure: a natural model for understanding variable disease severity in humans

Yet features distinguishing clinical outcomes such as heart failure and arterial thromboembolism remain poorly characterized. Using artificial intelligence-based digital pathology and Oxford Nanopore sequencing, we analyzed myocardial tissue from 37 cats grouped by outcome: arterial thromboembolism, congestive heart failure, or no documented cardiac disease.

Myocardial fibrosis was significantly higher in cats with arterial thromboembolism, indicating a distinct fibrotic phenotype. Cats with heart failure showed nuclear hypertrophy, while cats with arterial thromboembolism had increased numbers of small, hematoxylin-dense non-myocyte nuclei. Higher fibrosis was associated with downregulation of mitochondrial and cardiac conduction genes, and nuclear size correlated with proteostasis and stress-response pathways.