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

PURPOSE OF THE REVIEW: This review provides a framework for understanding autonomic neural regulation of cardiac function and dysfunction, highlighting the anatomical and functional organization of the autonomic nervous system, from intrinsic cardiac neurons to central cortical control centers. We review pathways leading to autonomic dysregulation in heart failure (HF) and cardiomyopathy (CMY), and we discuss the potential for precision neuromodulation informed by biomarkers and neuroimaging. RECENT FINDINGS: 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.