TARGETING THE NEURO-CARDIAC AXIS IN HYPERTENSIVE HEART DISEASE: CARDIAC SYMPATHETIC DENERVATION AS A MECHANISTICALLY AND CLINICALLY DIRECTED STRATEGY TO PREVENT OR REVERSE CARDIAC REMODELING

Objectives: Hypertensive heart disease (HHD) represents one of the most prevalent and devastating consequences of uncontrolled hypertension, characterized by progressive left ventricular hypertrophy (LVH), interstitial fibrosis, and diastolic dysfunction leading to heart failure with preserved ejection fraction (HFpEF). Sympathetic nervous system (SNS) overactivity has been identified as a central pathogenic mechanism linking sustained pressure overload to myocardial remodeling and impaired ventricular relaxation. This article proposes cardiac sympathetic denervation (CSD) as a mechanistically directed strategy to interrupt the maladaptive neuro-cardiac feedback loop in HHD and prevent or reverse cardiac remodeling.
Design: Conceptual hypothesis and narrative synthesis of translational and clinical evidence, integrating mechanistic pathways, preclinical data, and existing neuromodulation therapies to construct a mechanistic model and proposed experimental framework.
Setting: Not applicable; conceptual work based on published preclinical and clinical literature.
Participants: Not applicable; no human or animal subjects were directly enrolled. Proposed study populations are outlined for future experimental and clinical trials.
Interventions: Cardiac sympathetic denervation (surgical or catheter-based interruption of sympathetic efferent fibers from the stellate ganglia and upper thoracic chain), considered alongside other autonomic neuromodulatory interventions such as renal denervation (RDN), baroreflex activation therapy (BAT), and vagal nerve stimulation (VNS).
Primary and secondary outcome measures: This hypothesis paper outlines potential primary outcomes—including regression of left ventricular mass index and improvement in diastolic function—and secondary outcomes such as changes in autonomic indices, neurohormonal biomarkers, and fibrosis imaging parameters, to be evaluated in future translational and clinical trials.
Results: No empirical trial data are presented. Drawing on translational evidence from ventricular arrhythmia management, RDN, BAT, and VNS, this work synthesizes support for the concept that selective interruption of cardiac sympathetic outflow can mitigate myocardial stress, suppress neurohormonal activation, and promote regression of pathological remodeling. A multiphase experimental and clinical framework is described to test this hypothesis.
Conclusions: Targeted CSD may serve as a mechanistically guided, disease-modifying strategy for patients with early or advanced HHD by restoring autonomic balance and reducing neurohormonal overload. Validation of this hypothesis through structured preclinical and clinical programs could establish CSD—potentially in combination with complementary autonomic interventions such as nocturnal lower-limb elevation—as a next-generation therapy to alter the natural trajectory toward HFpEF.