Revival of Renal Denervation Therapy for Hypertension: Real Hope or just a Dream?

The sympathetic nervous system (SNS) has long been recognized as important to the initiation and maintenance of hypertension. From groundbreaking experimental physiology in the 1850s to single nerve fiber studies more than one 100 years later, the growing body of preclinical evidence supports this framework and has informed attempts at therapeutic clinical intervention. Prior to the availability of long-term oral antihypertensive therapy in the mid-1950s, operative approaches to SNS interruption were of variable efficacy and sometimes limiting side effects. Surgery was then abandoned as a panoply of drugs were introduced and shown to be effective in reducing blood pressure and, more importantly, decreasing major cardiovascular events. Despite the availability of dozens of agents, a small but significant percentage of patients do not achieve target pressures on multiple medications and are characterized as resistant or refractory. Nonsurgical, catheter-delivered radiofrequency ablation (RFA) to achieve renal SNS denervation has emerged as an option in these patients. Early clinical studies suggested marked reductions in office-based blood pressures. Results of the pivotal, sham-controlled SYMPLICITY HTN-3 study, however, were disappointing and did not show a significant difference in blood pressure reduction between treated and control groups. Post hoc analyses suggest that incomplete denervation was an important contributor to the much smaller blood pressure effect compared with earlier trials. Additional clinical anatomic and preclinical studies have greatly elucidated the distribution of sympathetic nerves in the renal periarterial space and provided insight into broad principles that might successfully move the field forward. A number of newer treatment platforms that include multielectrode RFA, focused high-energy ultrasound, and local periarterial delivery of neurolytics seem to justify the cautious enthusiasm that renal denervation (RDN) will eventually fulfill its promise in the treatment of resistant hypertension and perhaps other syndromes characterized by sympathetic overactivity.