Phenotypic patterns in feline heart failure: A natural model for understanding variable disease severity in humans
Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine
Summary Cats frequently develop myocardial remodeling, for example, hypertrophic cardiomyopathy, affecting 14.7% of domestic cats compared to 0.2% of humans, with shared genetic features making them relevant to human disease. 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. This multimodal framework reveals distinct histological and molecular profiles by outcome, with relevance for translational hypertrophic cardiomyopathy research. abs0010 Graphical abstract http://www.w3.org/1999/xlink float portrait ga1.jpg undfig1 anchor portrait graphical abs0015 Highlights • AI-based digital pathology quantifies myocardial remodeling in feline cardiac disease u0010 • Cats with arterial thromboembolism show increased myocardial
Abstract
Summary Cats frequently develop myocardial remodeling, for example, hypertrophic cardiomyopathy, affecting 14.7% of domestic cats compared to 0.2% of humans, with shared genetic features making them relevant to human disease. 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. This multimodal framework reveals distinct histological and molecular profiles by outcome, with relevance for translational hypertrophic cardiomyopathy research. abs0010 Graphical abstract http://www.w3.org/1999/xlink float portrait ga1.jpg undfig1 anchor portrait graphical abs0015 Highlights • AI-based digital pathology quantifies myocardial remodeling in feline cardiac disease u0010 • Cats with arterial thromboembolism show increased myocardial fibrosis and vascular changes u0015 • Distinct nuclear profiles characterize heart failure and thromboembolism outcomes u0020 • Nanopore RNA sequencing identifies gene pathways linked to myocardial tissue phenotypes u0025 simple ulist0010 author-highlights abs0020 Cardiovascular medicine; Veterinary medicine; Feline cardiology teaser abs0025