This review aims to describe the role and the results of catheter-based renal nerve ablation for the treatment of resistant hypertension. Despite the availability of multiple classes of orally active antihypertensive treatments, resistant hypertension remains an important public health issue in 2012 due to its prevalence and association with target-organ damage and poor prognosis. The failure of purely pharmacological approaches to treat resistant hypertension has stimulated interest in invasive device-based treatments based on old concepts. In the absence of orally active antihypertensive agents, patients with severe and complicated hypertension were widely treated by surgical denervation of the kidney until the 1960s, but this approach was associated with a high incidence of severe adverse events and a high mortality rate. A new catheter system using radiofrequency energy has been developed, allowing an endovascular approach to renal denervation and providing patients with resistant hypertension with a new therapeutic option that is less invasive than surgery and can be performed rapidly under local anaesthesia. To date, this technique has been evaluated only in open-label trials including small numbers of highly selected resistant hypertensive patients with suitable renal artery anatomy. The available evidence suggests a favourable blood pressure-lowering effect in the short term (6 months) and a low incidence of immediate local and endovascular complications. This follow-up period is, however, too short for the detection of rare or late-onset adverse events. For the time being, the benefit/risk ratio of this technique remains to be evaluated, precluding its uncontrolled and widespread use in routine practice.

Abstract The heart and kidney interact in terms of hemodynamics and neurohumoral regulatory mechanisms, and this helps to maintain circulatory homeostasis under normal conditions. However, the normal regulatory mechanisms become inappropriate in the setting of congestive heart failure (CHF), and significant renal dysfunction often develops in CHF patients. Activation of renal sympathetic efferent nerves causes renin release, sodium and water retention, and reduced renal blood flow, all hallmarks of the renal manifestations of CHF. An increase in plasma levels of angiotensin II that is mediated in part by renal sympathetic activation has an effect on the central nervous system to further increase global sympathetic tone. Renal sympathetic activity can be assessed clinically by renal norepinephrine spillover, and an increase in renal norepinephrine spillover in CHF predicts reduced survival. In addition to efferent sympathetic activation, activation of renal sensory nerves in CHF may cause a reflex increase in sympathetic tone that contributes to elevated peripheral vascular resistance and vascular remodeling as well as left ventricular remodeling and dysfunction. In animal models of heart failure, surgical renal denervation has been shown to improve both renal and ventricular function. Although surgical renal denervation has long been known to lower blood pressure and improve survival in patients with hypertension, the invasive nature of this approach and its associated complications has limited its appeal. However, a novel catheter-based device has recently been introduced that specifically interrupts both efferent and afferent renal nerves, and there is significant interest in the use of this device to treat both hypertension and CHF. Several ongoing clinical trials are investigating the safety and efficacy of renal denervation in patients with CHF.

Abstract Intrarenal injection of phenol in rats causes a persistent elevation in blood pressure (BP) and in norepinephrine (NE) secretion from the posterior hypothalamus (PH), and downregulation of neuronal nitric oxide synthase (nNOS) and interleukin-1β (IL-1β) in the PH. These studies suggest that afferent impulses from the kidney to the brain may be responsible for hypertension associated with renal injury. Downregulation of nNOS and IL-1β, two modulators of sympathetic nervous system (SNS) activity may mediate this activation. In this study we measured the effects of intrarenal phenol injection on peripheral SNS activity by direct renal nerve recording, plasma NE, nNOS, and IL - 1β abundance in the brain. We also determined whether renal denervation or administration of clonidine prevented these effects of phenol. Acutely, the phenol injection increased both afferent and efferent renal sympathetic nerve activity, decreased urinary sodium excretion, and increased plasma NE. Three weeks after the phenol injection, BP and plasma NE remained elevated. Renal denervation and pretreatment with clonidine prevented the increase in BP and plasma NE caused by phenol. Chronic renal injury caused by phenol was associated with decreased abundance of IL-1β and nNOS in the PH. These studies have shown that a renal injury caused by phenol injection increases BP and central as well as peripheral SNS activity, which persist long after the injury. Renal denervation and antiadrenergic drugs abolish the effects of phenol on BP and plasma NE. Because NO and IL-1β modulate SNS activity, the stimulatory action of phenol on the SNS could be mediated by downregulation of nNOS and IL-1β in the brain.

The purpose of the present study was to investigate the effects of long-term renal denervation (RD) on heart failure due to myocardial infarction (MI). Wistar rats were anesthetized and the bilateral renal nerves were surgically denervated 2 days before MI was induced by coronary artery ligation. Four weeks later, left ventricular (LV) function and sodium excretion were determined. In MI rats, RD improved the reduced sodium excretion. MI + RD rats revealed lower LV end-diastolic pressure and greater maximum d P /d t as compared with those of MI+ innervation (INN) rats. LV end-diastolic and end-systolic dimensions were significantly smaller and LV fractional shortening was greater in MI + RD rats than in MI + INN rats (20.9% ± 3.2% vs 14.9% ± 3.0%). In rats without MI, RD did not affect either sodium excretion or LV function and dimensions. The present results suggest that the long-term RD reduces LV filling pressure and improves LV function after MI, probably due to a restoration of impaired natriuresis. Increased renal sympathetic nerve activity might contribute to the progression of heart failure after MI.

Invasive device-based therapies for drug-resistant hypertension are undergoing active clinical investigation. The two approaches are 1) permanent implantation of a carotid baroreceptor pacemaker and 2) radiofrequency catheter ablation of the renal nerves. Both are designed to reduce the sympathetic nervous system component of drug-resistant hypertension. Several excellent comprehensive articles have reviewed each of these devices separately. In contrast, this brief article aims to provide a conceptual framework for evaluating the premise, promise, and potential limitations of both invasive antihypertensive therapies.

Background   Renal sympathetic hyperactivity is associated with hypertension, a leading cause of mortality worldwide. Renal sympathetic denervation via the Symplicity Catheter System has been shown to decrease blood pressure by 33/11 mmHg by 6 months, with no radiofrequency (RF)-related adverse sequelae visible by CT/MR angiography or renal duplex ultrasound 6 months after the procedure. Here, we present preclinical work predating those clinical results. We performed therapeutic renal sympathetic denervation in a swine animal model to characterize the vascular safety and healing response 6 months after renal denervation therapy.

Résumé L’hypertension artérielle (HTA) est un problème de santé publique majeur qui affecte entre 30 et 40 % de la population adulte des pays industrialisés. En dépit des nombreux traitements pharmacologiques disponibles, l’HTA demeure trop souvent incontrôlée. Un pourcentage non négligeable de patients souffrant d’HTA reste réfractaire aux polythérapies médicamenteuses, ce qui les expose à un risque accru de survenue d’événements cardiovasculaires. La dénervation rénale par voie endocavitaire utilisant un cathéter porteur d’une sonde de radiofréquence à basse énergie permet en diminuant les afférences nerveuses de réduire la pression artérielle chez ces patients résistants. Les patients qui peuvent bénéficier de cette technique doivent avoir une HTA essentielle non équilibrée malgré un traitement comprenant au moins la prise d’une trithérapie anti-hypertensive dont un diurétique, et doivent avoir une filtration glomérulaire supérieure ou égale à 45 mL/min. Une première étude sous forme de registre a d’abord montré que la dénervation rénale par ablation était une intervention simple, sûre, et permettait une réduction significative et durable de la pression artérielle. Puis, une étude randomisée contre témoin (l’essai Symplicity HTN-2), a montré que les chiffres tensionnels du groupe bénéficiant de l’intervention ont baissé en moyenne de 32/12 mmHg, alors qu’aucune variation n’a été constatée dans le groupe témoin. Cette baisse de la pression artérielle persistait à 24 mois de suivi. Aucune complication associée à la procédure, aucune sténose de l’artère rénale ou dilatation anévrismale n’ont été mises en évidence au cours du suivi. Il n’a pas été non plus observé d’altération ou d’aggravation de la fonction rénale. Cette technique semble donc représenter un véritable espoir pour ces patients graves. Nous rapportons le cas de deux patients traités par cette technique dans notre centre et qui concrétise le réel apport de cette technique. Abstract Arterial hypertension is a major healthcare issue affecting between 30 and 40% of the adult population in industrialized countries. Despite the availability of numerous pharmaceutical treatments, arterial hypertension often remains uncontrolled. A non-negligible percentage of patients are refractory to multiple-drug therapy, which exposes them to an increased risk of cardiovascular events. Percutaneous, renal denervation using a catheter connected to a low energy radiofrequency generator has proven effective in decreasing arterial pressure in patients resistant to medical therapy, by reducing afferent nerve activity. In order to be eligible for this therapeutic approach, patients must have uncontrolled essential hypertension despite treatment with a combination of three anti-hypertensive drugs including a diuretic agent, and ≥ 45 mL/min glomerular filtration rate. The initial registry study demonstrated that catheter-based sympathetic renal denervation was a simple and safe procedure resulting in a significant and durable reduction in arterial pressure. Subsequently, a randomized controlled trial (the Symplicity HTN-2 trial) showed a mean 32/12 mmHg decrease in blood pressure measurements in the group of patients who underwent renal denervation whereas no difference was observed in the control group. The reduction in blood pressure was still present at 24-month follow-up. No procedure-related complications were reported and no instances of renal artery stenosis or aneurysmal dilatation were evidenced during the follow-up period. No cases of renal function impairment or deterioration were recorded. This technique seems to be a promising strategy in patients suffering from this serious condition. In order to demonstrate the actual benefit of this technique, we report the case of two patients who underwent renal denervation in our institution.