Ultrasound-based renal sympathetic denervation for the treatment of therapy-resistant hypertension: a single-center experience.

INTRODUCTION: The effectiveness of renal sympathetic denervation (RDN) as a treatment for therapy-resistant hypertension has been doubted as the Simplicity-HTN-3 trial was unable to show any treatment benefit over sham procedure. This might partly be explained by a high procedural variability in treatment with radiofrequency-based catheters. Recently, newer systems for RDN, like ultrasound-based devices, have been introduced into practice. To date however, data on their effectiveness for the treatment of resistant hypertension are scarce. We sought to evaluate the safety and effectiveness of an ultrasound-based, balloon-irrigated RDN catheter in a larger single-center cohort. METHODS: Patients with therapy-resistant hypertension [average blood pressure (BP) >135 mmHg SBP or >90 mmHg DBP in ambulatory BP measurement despite at least three antihypertensive drugs, including at least one diuretic] underwent ultrasound-based RDN. Treatment effect was assessed by comparing BP values at baseline and 3 months after the procedure. Patients underwent renal artery duplex sonography or MRI before and after RDN to exclude renal artery stenosis. RESULTS: Fifty consecutive patients underwent ultrasound-based RDN, of which 25 had undergone an unsuccessful radiofrequency RDN before. Mean SBP change at 3 months was -9.7 ±â€Š12.6/-10.6 ±â€Š13.7/-8.2 ±â€Š15.2 mmHg (ambulatory 24-h mean/daytime/night, P < 0.001 for all) and DBP changed by -5.1 ±â€Š7.4/-5.8 ±â€Š7.8/-3.9 ±â€Š10.3 mmHg (P ≤ 0.001/<0.001/0.01). No new renal artery stenosis could be detected after RDN. CONCLUSION: Ultrasound-based RDN seems to be well tolerated and effective for the treatment of patients with therapy-resistant hypertension.

Renal sympathetic denervation in therapy resistant hypertension - pathophysiological aspects and predictors for treatment success.

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.

Invasive aortic pulse wave velocity as a marker for arterial stiffness predicts outcome of renal sympathetic denervation.

AIMS: A recurrent finding of trials on renal sympathetic denervation is a certain percentage of non-responders. The aim of this study was to examine the influence of arterial stiffness to predict response. METHODS AND RESULTS: Eighty-eight patients were included in the study. Arterial stiffness was measured by invasive pulse wave velocity. Antihypertensive medication had to be unchanged during follow-up. Ambulatory blood pressure measurement (ABPM) was used to record blood pressure before and six months after denervation. Fifty-eight patients without changes in medication were included in the final analysis. Responders (n=37; blood pressure reduction -12.8±6.4 mmHg) had a significantly lower pulse wave velocity (14.4±4.4 m/s versus 17.7±4.5 m/s; p=0.009) compared to non-responders (n=21; blood pressure reduction +3.0±4.5 mmHg; p<0.001 for comparison with responders). In multivariate analysis, invasive pulse wave velocity was the only significant predictor of blood pressure reduction after denervation (odds ratio 1.15, 95% confidence interval [CI] 1.014-1.327; p=0.03). Patients with increased stiffness were older (p=0.001), had a higher prevalence of diabetes (p=0.008), more often had isolated systolic hypertension (p=0.007), and had a higher invasive pulse pressure (p<0.001). CONCLUSIONS: 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.

Endovascular ultrasound for renal sympathetic denervation in patients with therapy-resistant hypertension not responding to radiofrequency renal sympathetic denervation.

AIMS: Recent studies have reported a considerable number of non-responders after renal sympathetic de-nervation (RSD) with radiofrequency technology. Here we report our results of repeat RSD using ultrasound in these patients. METHODS AND RESULTS: A cohort study was performed in patients who underwent ultrasound RSD after non-response to RSD with radiofrequency. Non-response was defined as mean daytime systolic blood pressure ≥140 mmHg and/or a reduction of ≤10 mmHg in ambulatory blood pressure measurement (ABPM) ≥6 months after radiofrequency denervation. ABPM was recorded at baseline, post radiofrequency RSD as well as at three and six months post ultrasound RSD. A total of 24 non-responders underwent retreatment with the ultrasound device at a mean 15.3±8.2 months after radiofrequency RSD. Ultrasound RSD was performed successfully in all patients without severe adverse events. Mean daytime systolic blood pressure changed from 161.7±14.6 mmHg at baseline to 158.5±9.5 mmHg post radiofrequency RSD and to 150.5±10.4 mmHg and 151.6±11.0 mmHg at three and six months, respectively, post ultrasound RSD (p<0.01 with repeated measures analysis of variance). The main results of post hoc testing were as follows: baseline versus post radiofrequency RSD, p=0.83; baseline versus three months post ultrasound RSD, p=0.01; and baseline versus six months post ultrasound RSD, p=0.04. CONCLUSIONS: Ultrasound RSD appears to be safe and an effective therapeutic approach in patients not responding to previous RSD with radiofrequency technology.

Renal denervation improves exercise blood pressure: insights from a randomized, sham-controlled trial.

INTRODUCTION: Despite the ongoing debate on the role of renal sympathetic denervation (RSD) in the management of therapy-resistant hypertension, little is known about its possible effects on exercise blood pressure (BP), a known predictor for future cardiovascular events. We sought to evaluate the effect of RSD on exercise BP in a randomized, sham-controlled trial in patients with mild hypertension. METHODS AND RESULTS: Patients with therapy-resistant mild hypertension (defined by mean daytime systolic BP between 135 and 149 mmHg or mean daytime diastolic BP between 90 and 94 mmHg on 24-h ambulatory BP measurement) were randomized to either radiofrequency-based RSD or a sham procedure. Patients underwent cardiopulmonary exercise testing at baseline and after 6 months. Of the 71 patients randomized, data from cardiopulmonary exercise testing were available for 48 patients (22 in the RSD group, 26 in the sham group). After 6 months, patients undergoing RSD had a significantly lower systolic BP at maximum exercise workload compared to baseline (-14.2 ± 26.1 mmHg, p = 0.009). In contrast, no change was observed in the sham group (0.6 ± 22.9 mmHg, p = 0.45, p = 0.04 for between-group comparison). When analyzing patients with exaggerated baseline exercise BP only, the effect was even more pronounced (RSD vs. sham -29.5 ± 23.4 vs. 0.1 ± 25.3 mmHg, p = 0.008). CONCLUSION: Exercise systolic BP values in patients with mild therapy-resistant hypertension are reduced after RSD as compared to a sham-procedure.

Renal sympathetic denervation in uncontrolled arterial hypertension after successful repair for aortic coarctation.

BACKGROUND: Uncontrolled arterial hypertension is a frequent problem after successful repair of CoA and has been attributed to increased central sympathetic drive as well as a blunted baroreceptor reflex. RSD is a promising therapy to reduce central sympathetic drive and improve baroreflex sensitivity. METHODS: 8 patients (age: 27±6 years) with previous surgical and/or percutaneous repair of CoA, absence of any relevant restenosis (invasive gradient across the site of previous treatment 3±4 mmHg) and resistant arterial hypertension (daytime SBP≥140 mmHg on 24 hour ambulatory blood pressure measurements [ABPM] in spite of the concurrent use of 3 antihypertensive agents of different classes or intolerance to BP medications) were included. Bilateral RSD was performed using the Symplicity Flex™ catheter (Medtronic, MN, USA). RESULTS: RSD was successful in all patients with no procedural complications and no evidence for renal artery stenosis 6 months post procedure. From baseline to 6 month follow-up, RSD was followed by a significant reduction in average daytime systolic BP (150.4±7.8 to 143.1±8.0 mmHg; p=0.0117) as well as systolic BP throughout 24 h (146.8±7.3 vs. 140.5±7.8, p=0.04). CONCLUSION: The BP reductions observed in these patients justify engaging in a larger clinical trial on the efficacy of RSD in this specific type of secondary hypertension and bares the hope that RSD might extend the currently very limited armory against arterial hypertension in young adults with previous repair of CoA.

Randomized sham-controlled trial of renal sympathetic denervation in mild resistant hypertension.

UNLABELLED: 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 population. A total of 71 patients underwent randomization. Baseline day-time systolic BP was 144.4±4.8 mm Hg in patients assigned to denervation and 143.0±4.7 mm Hg in patients randomized to the sham procedure. The mean change in 24-hour systolic BP in the intention to treat cohort at 6 months was -7.0 mm Hg (95% confidence interval, -10.8 to -3.2) for patients undergoing denervation and -3.5 mm Hg (95% confidence interval, -6.7 to -0.2) in the sham group (P=0.15). In the per protocol population, the change in 24-hour systolic BP at 6 months was -8.3 mm Hg (95% confidence interval, -11.7 to -5.0) for patients undergoing denervation and -3.5 mm Hg (95% confidence interval, -6.8 to -0.2) in the sham group (P=0.042). In patients with mild resistant hypertension, renal sympathetic denervation failed to show a significant reduction in the primary end point of 24-hour systolic BP at 6 months between groups in the intention to treat analysis. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01656096.