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

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  Figure 1. Integrated network model of multiorgan crosstalk in chronic heart failure. Schematic representation of the failing heart as a central node within a dynamic multiorgan interaction network. Bidirectional signaling occurs between the myocardium and peripheral organ systems, including the gastrointestinal tract (heart–gut axis), skeletal system (heart–bone axis), vascular endothelium (heart–vascular axis), and central/autonomic nervous system (neurocardiac axis). Reduced cardiac output and venous congestion contribute to intestinal barrier dysfunction and microbial translocation, amplifying systemic inflammation. Bone-derived mediators such as osteoprotegerin and osteocrin participate in endocrine and vascular signaling. Endothelial activation and vasoactive mediators modulate organ perfusion and inflammatory amplification. Autonomic imbalance, characterized by sympathetic overactivation and vagal withdrawal, links cardiac dysfunction to arrhythmogenesis and neuroimmune modulation.

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  Figure 2. Bidirectional translational framework integrating spontaneous canine heart failure and experimental in vivo models. Naturally occurring canine heart failure, including myxomatous mitral valve disease and dilated cardiomyopathy, provides clinically relevant and heterogeneous disease phenotypes characterized by longitudinal remodeling, neurohormonal activation, and systemic involvement. These spontaneous models allow comprehensive phenotyping through echocardiography, circulating biomarkers, and clinical outcome assessment. Complementary experimental in vivo models, including anthracycline-induced cardiomyopathy and cardiopulmonary bypass systems, enable temporal control of myocardial injury and mechanistic interrogation of endothelial activation, inflammatory signaling, and multiorgan interactions. The integration of clinical observation and experimental validation establishes a bidirectional translational platform. Clinical findings generate mechanistic hypotheses, while controlled models refine causal inference and therapeutic targeting. This iterative framework positions veterinary cardiology as a contributor to comparative cardiovascular science and supports the development of…