Scope of the Expert Consensus Statement
Resistant hypertension is a common and growing yet neglected clinical problem. General practitioners and specialist physicians are frequently faced with the challenging task of managing these patients. A novel interventional treatment approach based on transluminal radiofrequency (RF) ablation of renal nerves has recently been introduced into clinical medicine in Australia, Europe, and other countries and has sparked substantial interest from affected patients, treating and referring practitioners and physicians, interventionalists, and health care providers. In view of the limited clinical trial data available, it appeared timely and important to summarize the views of an international panel to provide some guidance with regard to the indications, methods, and safety of transluminal renal nerve ablation. The recommendations in this statement are based on the interpretation of clinical trial data available to date and are intended to facilitate a better understanding of the safety, effectiveness, and limitations of this technology, with a particular focus on appropriate patient selection.
There is a lack of data on the exact prevalence of resistant hypertension, which is commonly defined as blood pressure (BP) higher than target levels despite the use of 3 antihypertensive agents in adequate doses from different classes, including a diuretic agent. Evidence from the National Health and Nutrition Examination Survey and from large randomized clinical trials indicates that 20% to 30% of patients with hypertension require 3 or more antihypertensive agents to achieve BP targets. Recent data from the National Health and Nutrition Examination Survey indicate that 12.8% of the antihypertensive drug–treated population fulfilled the criteria of resistant hypertension. Data from a large Spanish registry suggested that resistant hypertension is present in 12% of the treated hypertensive population, but among them, more than one-third have normal ambulatory BP. Data from 205,750 patients with incident hypertension revealed that 1.9% developed resistant hypertension within a median of 1.5 years from initial treatment (0.7 cases per 100 person-years of follow-up). Failure to reach target BP levels despite therapeutic intervention leaves patients at high risk for major cardiovascular events.
Sympathetic Nervous System and BP Control
The sympathetic nervous system plays an important role in circulatory and metabolic control and is a major contributor to the development of hypertension, mediated via sodium and water retention, increased renin release, and alterations of renal blood flow. Accordingly, direct targeting of the sympathetic nervous system is a logical therapeutic approach for the treatment of hypertension.
Specific Role of Renal Nerves for Hypertension and Cardiovascular Outcomes
The kidneys have a dense afferent sensory and efferent sympathetic innervation. Renal sensory afferent nerve activity directly influences sympathetic outflow to the kidneys and other highly innervated organs involved in cardiovascular control (Fig. 1). Afferent and efferent sympathetic nerves can interact to modulate sympathetic activity. Abrogation of renal sensory afferent nerves reduces both BP and organ-specific damage caused by chronic sympathetic overactivity in various experimental models. Although afferent activity cannot be quantified in humans, there is strong evidence that it modulates the level of central sympathetic outflow. Assessment of regional overflow of norepinephrine (NE) from the kidneys to plasma has demonstrated that renal NE spillover rates can be markedly elevated in patients with essential hypertension and are associated with hypertensive end-organ damage such as left ventricular hypertrophy.
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Figure 1.
Effects of Afferent Renal Nerve Signaling
Various triggers, such as renal injury and ischemia, can stimulate afferent signaling from the kidney to central integrative nuclei, with the consequence of exaggerated efferent sympathetic outflow to target organs, including the heart, the vasculature, the kidneys, and other organs involved in both cardiovascular and metabolic control, as illustrated. Renal denervation, by targeting both efferent and afferent nerves as can be achieved by catheter-based application of radiofrequency energy, may be useful to effectively interrupt this vicious cycle. OSA = obstructive sleep apnea; pCO2 = partial pressure of carbon dioxide; RAAS = renin-angiotensin-aldosterone system.