Autonomic Imbalance in Cardiomyopathy and Heart Failure: From Neurobiology to Precision Neuromodulation

We synthesize emerging insights into the molecular, inflammatory, and psychological mechanisms contributing to autonomic dysregulation in HF, and examine the clinical implications of impaired reflex arcs and persistent neurohormonal activation. Recent advances in neuromodulation, including vagus nerve stimulation, baroreflex activation therapy, spinal cord stimulation, cardiac sympathetic denervation and cortical neuromodulation demonstrate the potential to restore autonomic balance and improve HF outcomes. Autonomic imbalance, characterized by sympathetic overactivation and parasympathetic withdrawal, is a hallmark of HF and CMY, contributing to disease progression and adverse outcomes. While traditional pharmacotherapies target downstream neurohormonal pathways, neuromodulation offers the opportunity to intervene upstream, directly at pathophysiological nexus points. Ultimately, a shift toward personalized, circuit-specific neuromodulation strategies may offer new opportunities for treating autonomic dysregulation in HF and CMY.