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.

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.

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.