Central neuromodulation as a therapeutic tool for cardiac dysfunction

Cardiac dysfunction—spanning heart failure, malignant arrhythmias, and autonomic imbalance—remains a leading cause of morbidity andmortality despite advances in pharmacological and device-based therapies. Over the past three decades, the concept of a distributed brain–heart axis, mediated by the central autonomic network (CAN), has reframed cardiovascular disease as a disorder of integrated neurocardiacregulation rather than a purely peripheral organ failure. Central neuromodulation—via deep brain stimulation (DBS), vagus nerve stimulation(VNS), transcranial magnetic stimulation (TMS), and transcranial direct current stimulation (tDCS)—has emerged as a strategy to restoreautonomic balance, dampen neuroinflammation, and modulate neuroendocrine and electrophysiological pathways that drive cardiacdysfunction. This review synthesizes current knowledge on the physiology of the brain–heart axis, mechanistic underpinnings of centralneuromodulation, and evidence from preclinical and clinical studies targeting cardiac outcomes. We summarize key trials of VNS in heartfailure, early data on neuromodulation for arrhythmias and hypertension, and the emerging role of non-invasive cortical stimulation inautonomic modulation. Limitations of existing studies—including heterogeneous stimulation parameters, small sample sizes, and incompletemechanistic mapping—are critically examined. Finally, we outline future directions, including closed-loop neuromodulation, AI-guidedparameter optimization, and integration with neuroimaging and wearable cardiac monitoring. Central neuromodulation is unlikely to replaceconventional therapies, but it may become a powerful adjunct in selected patients with high autonomic burden and refractory cardiac disease