Renal Denervation in Cardiovascular Diseases: Mechanisms, Evidence, and Expanding Applications

Renal denervation (RDN) is a minimally invasive technique that disrupts renal sympathetic nerve activity, reducing sympathetic overdrive implicated in hypertension and other cardiovascular disorders. After early enthusiasm waned following SYMPLICITY HTN-3, subsequent rigorously designed trials re-established its efficacy. This review summarizes mechanistic insights, clinical evidence, and emerging applications of RDN. Data from randomized trials, meta-analyses, registries, and translational studies were evaluated to assess their safety, efficacy, and broader therapeutic potential. Recent trials (SPYRAL HTN-OFF MED, RADIANCE HTN-TRIO, RADIANCE II) show consistent and durable systolic blood pressure reductions of approximately 5-10 mmHg with excellent safety. Beyond resistant hypertension, preliminary studies suggest benefits in heart failure (HFrEF and HFpEF), atrial fibrillation when combined with pulmonary vein isolation, chronic kidney disease, and metabolic syndrome. Mechanistic data reveal improved autonomic balance, regression of left ventricular hypertrophy, and possible renal protection. Limitations include procedural variability, incomplete nerve ablation, and the lack of large outcome-based cardiovascular trials. Nevertheless, cost-effectiveness analyses and recent ESC (2024) and AHA/ACC (2025) guidelines endorse RDN as a reasonable adjunct for resistant or uncontrolled hypertension. RDN offers sustained blood pressure control with a strong safety profile. Its expanding role across cardiovascular conditions positions it as a promising adjunctive therapy. Future outcome-driven studies and standardized procedural approaches are needed to refine its place in clinical practice.