Catheter-based renal sympathetic denervation: a targeted approach to resistant hypertension.

Abstract

Hypertension is a growing public health concern for which successful treatment often remains elusive. In the United States, an estimated one in three adults has hypertension and the global prevalence continues to climb, particularly in developing countries [1, 2]. Despite access to pharmacological therapies and resources to help patients achieve necessary lifestyle modifications, approximately half of patients fail to achieve recommended target blood pressure values [1]. This can perhaps be attributed to patient non-adherence as a result of physician inertia, polypharmacy, adverse drug events and patient resistance to a lifelong regimen for a largely asymptomatic disease. More than 50 years of drug development has worked to the benefit of many hypertensive patients. But such development has slowed and the time has come to consider non-drug therapies for this rampant disease. New therapeutic approaches that will overcome these obstacles are essential [3, 4]. A small, but significant, percentage of patients [5] with uncontrolled hypertension fail to meet therapeutic targets despite taking multiple drug therapies at the highest tolerated doses, a phenomenon called ‘resistant hypertension’. This may suggest underlying pathophysiology resistant to current pharmacological approaches [4]. Innovative therapeutic approaches are particularly relevant for these patients, as their condition puts them at high risk of major cardiovascular events [6]. Renal afferent and sympathetic efferent nerves have been implicated in the pathophysiology of systemic hypertension [7–10]. As a result, a succession of therapeutic approaches have targeted the sympathetic nervous system to modulate hypertension, with varying success. Many of these early approaches involved radical sympathetic denervation, failing to target specific organs thought to be directly involved with the pathophysiology of the disease. While successful in reducing blood pressure, the broad nature of these approaches led to many perioperative and long-term complications, including bowel, bladder and erectile dysfunction, as well as the dreaded side-effect of postural hypotension [11–13]. But a more targeted approach of renal sympathetic denervation remains a potential therapeutic option and is emerging as a subject of active research. Recent studies have aimed to assess the safety and efficacy of a percutaneous, catheter-based approach designed to specifically ablate renal sympathetic nerves using a radiofrequency generator via the lumen of the main renal artery. In a safety and proof-of-principle study, and a separate randomized controlled trial, both published in the Lancet, in 2009 and 2010 respectively, this approach was shown to successfully reduce blood-pressure, without serious adverse events in patients with resistant hypertension [3, 4]. This article will review the recent literature regarding catheter-based renal ablation in the context of current knowledge of the pathophysiology of resistant hypertension, and will explore future directions for research regarding this new approach.