Kuznetsova Anna¹, Okada Ren², Haque Samira³, Mendes Bruno⁴, Vogel Leon⁵, Rousseau Claire⁶
ABSTRACT:
Background: Chronic heart failure (CHF) is increasingly recognized as a systemic syndrome involving bidirectional interactions between the cardiovascular and central nervous systems. The brain-heart axis plays a critical role in regulating cardiac function through complex neurohumoral, autonomic, and inflammatory signaling pathways. Dysregulation of this axis contributes to disease progression, symptom burden, and adverse outcomes. Neurohormonal overactivation—especially of the sympathetic nervous system and hypothalamic-pituitary-adrenal (HPA) axis—leads to persistent vasoconstriction, fluid retention, and cardiomyocyte injury. In parallel, systemic inflammation and altered brain-derived cytokine profiles exacerbate myocardial remodeling and impair central autonomic control. Methods and Results: This review synthesizes mechanistic and clinical evidence on the role of the brain-heart axis in CHF, with a focus on neurohumoral mediators such as norepinephrine, cortisol, vasopressin, and natriuretic peptides, as well as proinflammatory cytokines including IL-1β, IL-6, and TNF-α. Functional neuroimaging and biomarker studies reveal structural and metabolic alterations in brain regions governing autonomic and emotional regulation, including the insula, anterior cingulate cortex, and hypothalamus. These changes correlate with elevated sympathetic outflow, heart rate variability reduction, and increased mortality. Emerging therapeutic strategies—such as vagus nerve stimulation, anti-inflammatory agents, and centrally acting modulators—demonstrate potential to restore neurocardiac homeostasis and improve clinical outcomes. Conclusion: The brain-heart axis constitutes a central pathophysiological mechanism in chronic heart failure, bridging autonomic imbalance, neuroendocrine dysregulation, and systemic inflammation. Integrating neural and cardiac biomarkers may refine phenotyping and enable personalized therapeutic interventions targeting both cardiac and central dysfunction. A deeper understanding of brain-heart crosstalk offers new avenues for disease modification in CHF management.