Reframing Heart Failure as a Multiorgan Network Disorder: Translational and Regenerative Perspectives in Veterinary Cardiology

Abstract

Heart failure (HF) has traditionally been regarded as a primary myocardial disorder in veterinary medicine. However, accumulating evidence suggests that HF represents a systemic syndrome characterized by dynamic multiorgan interactions. In human cardiovascular research, cardiorenal and cardiointestinal paradigms have reshaped disease conceptualization, yet comparable integrative frameworks remain underdeveloped in veterinary cardiology. Naturally occurring canine HF—particularly myxomatous mitral valve disease and dilated cardiomyopathy—offers a clinically relevant translational platform in which systemic remodeling unfolds within an intact physiological lifespan. This review proposes a systems-based perspective that integrates spontaneous canine HF with controlled in vivo experimental models. We outline four main pathways of interaction: (1) the heart–gut axis, wherein reduced perfusion can influence inflammation and disruption of the intestinal barrier; (2) the heart–bone axis, wherein endocrine factors like osteoprotegerin and osteocrin can impact remodeling of the cardiovascular system; (3) the heart–vascular endothelium axis, wherein inflammatory signaling and dysfunction of the vascular endothelium are hallmarks; and (4) the neurocardiac axis, which reflects an imbalance in the autonomic nervous system. Emerging regenerative and organelle-based strategies—including mesenchymal stem cell therapy and mitochondrial transplantation—are discussed within this multiorgan framework. Rather than focusing solely on cardiac contractility, these approaches may function as systemic inflammatory modulators, and endothelial, metabolic, and autonomic pathways. Canine HF can be better understood as a multiorgan network condition; reframing it in this way can help researchers in the field of translational cardiology create more comprehensive diagnostic and treatment plans.