Modulation of renal sympathetic innervation: recent insights beyond blood pressure control

Renal afferent and efferent sympathetic nerves are involved in the regulation of blood pressure and have a pathophysiological role in hypertension. Additionally, several conditions that frequently coexist with hypertension, such as heart failure, obstructive sleep apnea, atrial fibrillation, renal dysfunction, and metabolic syndrome, demonstrate enhanced sympathetic activity. Renal denervation (RDN) is an approach to reduce renal and whole body sympathetic activation. Experimental models indicate that RDN has the potential to lower blood pressure and prevent cardio-renal remodeling in chronic diseases associated with enhanced sympathetic activation. Studies have shown that RDN can reduce blood pressure in drug-naïve hypertensive patients and in hypertensive patients under drug treatment. Beyond its effects on blood pressure, sympathetic modulation by RDN has been shown to have profound effects on cardiac electrophysiology and cardiac arrhythmogenesis. RDN can display anti-arrhythmic effects in a variety of animal models for atrial fibrillation and ventricular arrhythmias. The first non-randomized studies demonstrate that RDN may promote the maintenance of sinus rhythm following catheter ablation in patients with atrial fibrillation. Registry data point towards a beneficial effect of RDN to prevent ventricular arrhythmias in patients with heart failure and electrical storm. Further large randomized placebo-controlled trials are needed to confirm the antihypertensive and anti-arrhythmic effects of RDN. Here, we will review the current literature on anti-arrhythmic effects of RDN with the focus on atrial fibrillation and ventricular arrhythmias. We will discuss new insights from preclinical and clinical mechanistic studies and possible clinical implications of RDN.