R esistant hypertension is defined as a blood pressure (BP) of ≥140/90 mm Hg despite the intake of ≥3 antihypertensive drugs, including a diuretic at maximally tolerated doses. 1 Its prevalence has been reported to be 12.8% in a US population.2 Sympathetic overactivity contributes to the development and perpetuation in a subset of patients with resistant hypertension.3 Its negative effects include sodium and water retention, increased renin release, and alterations of renal blood flow. 3Afferent and efferent sympathetic nerves that travel in the renal artery walls mediate pathological interactions between the central nervous system and the kidneys. Recently, catheterbased disruption of these renal sympathetic nerve fibers using radiofrequency energy has been introduced as a new treatment against resistant hypertension. Initial nonrandomized and randomized, nonblinded trials demonstrated a dramatic reduction in systolic and diastolic BP after renal sympathetic denervation (RSD). 4,5 In contrast, in the recent sham-controlled Simplicity HTN-3 trial of patients with severe treatment-resistant hypertension, RSD led to no significant improvement in BP when compared with the sham group.6 Some think that the results of this trial with the so far most rigorous design commenced the beginning of the end of RSD for resistant hypertension. Proponents of RSD argue that the negative outcome is a consequence of inefficient denervation procedures and suboptimal selection of patients. One aspect that deserves further consideration is that patients recruited into the Simplicity HTN-3 study might represent a population at the most advanced spectrum of the disease with marked and in many cases long-standing hypertension. One could argue that in such patients, RSD might be less effective because of irreversible alterations of the anatomic structures and physiological processes supporting chronic BP elevations. The present trial was conducted to test the hypothesis that RSD is superior to a sham intervention in patients with only mild resistant arterial hypertension. Methods Design OverviewThe trial's main objective was to study a possible blood-pressure lowering effect of RSD in patients with resistant hypertension and mildly elevated BP. Eligible patients between 18 and 75 years of age were randomized to RSD or a sham procedure. Resistant hypertension with mildly elevated BP was defined as (1) a stable antihypertensive drug Abstract-Few data are available with regard to the effectiveness of renal sympathetic denervation in patients with resistant hypertension yet only mildly elevated blood pressure (BP). Patients with resistant hypertension and slightly elevated BP (day-time systolic pressure, 135-149 and diastolic pressure, 90-94 mm Hg on 24-hour ambulatory measurement) were randomized in a 1:1 ratio to renal sympathetic denervation with the Symplicity Flex Catheter (Medtronic) or an invasive sham procedure. The primary efficacy end point was the change in 24-hour systolic BP at 6 months between groups in the intention to treat po...

Patients with lower pulse wave velocity showed a significantly better response to denervation. These findings emphasise that pulse wave velocity might be used as a selection criterion for renal denervation.

Exercise systolic BP values in patients with mild therapy-resistant hypertension are reduced after RSD as compared to a sham-procedure.

Many forms of human hypertension are associated with an increased systemic sympathetic activity. Especially the renal sympathetic nervous system has been found to play a prominent role in this context. Therefore, catheter-interventional renal sympathetic denervation (RDN) has been established as a treatment for patients suffering from therapy resistant hypertension in the past decade. The initial enthusiasm for this treatment was markedly dampened by the results of the Symplicity-HTN-3 trial, although the transferability of the results into clinical practice to date appears to be questionable. In contrast to the extensive use of RDN in treating hypertensive patients within or without clinical trial settings over the past years, its effects on the complex pathophysiological mechanisms underlying therapy resistant hypertension are only partly understood and are part of ongoing research. Effects of RDN have been described on many levels in human trials: From altered systemic sympathetic activity across cardiac and metabolic alterations down to changes in renal function. Most of these changes could sustainably change long-term morbidity and mortality of the treated patients, even if blood pressure remains unchanged. Furthermore, a number of promising predictors for a successful treatment with RDN have been identified recently and further trials are ongoing. This will certainly help to improve the preselection of potential candidates for RDN and thereby optimize treatment outcomes. This review summarizes important pathophysiologic effects of renal denervation and illustrates the currently known predictors for therapy success.

Ultrasound RSD appears to be safe and an effective therapeutic approach in patients not responding to previous RSD with radiofrequency technology.

Ultrasound-based RDN seems to be well tolerated and effective for the treatment of patients with therapy-resistant hypertension.

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