Renal Denervation for Treating Hypertension: Current Scientific and Clinical Evidence.

Initial studies of catheter-based renal denervation (RDN) for uncontrolled HTN using radiofrequency ablation in the main renal arteries showed that RDN was effective in lowering office blood pressure (BP). However, the first randomized sham-controlled trial, SYMPLICITY-HTN-3, did not show significantly lower office or 24-h ambulatory systolic BP compared with sham treatment. Subsequent studies in both animals and humans demonstrated the potential importance of more distal and branch renal artery radiofrequency ablation, and a second-generation multielectrode system became available. Two recent randomized sham-controlled trials in patients not taking antihypertensive drugs (SPYRAL HTN-OFF MED) or continuing to take drugs (SPYRAL HTN-ON MED) performed RDN with the second-generation radiofrequency ablation system using an ablation protocol that included treatment of the distal renal artery as well as the branch renal arteries. These studies showed that RDN significantly reduced office and 24-h ambulatory BP compared with sham treatment. Another recent randomized sham-controlled trial in patients not receiving medications showed that RDN with catheter-based ultrasound (RADIANCE-HTN SOLO) applied in just the main renal arteries significantly lowered daytime ambulatory and office BP compared with sham treatment. These trials have renewed clinical and scientific interest in defining the appropriate role of RDN in hypertension treatment. In addition, other important issues will need to be addressed in the future such as the development of tests to determine the extent of RDN at the time of the procedure and the potential of renal nerve fibers to regain their patency at some later stage following the ablation procedure.

Weber MA ，Mahfoud F ，Schmieder RE ，Kandzari DE ，Tsioufis KP ，Townsend RR ，Kario K ，Böhm M ，Sharp ASP ，Davies JE ，Osborn JW ，Fink GD ，Euler DE ，Cohen DL ，Schlaich MP ，Esler MD ... -  《-》

A Three-Arm Randomized Trial of Different Renal Denervation Devices and Techniques in Patients With Resistant Hypertension (RADIOSOUND-HTN).

Fengler K ，Rommel KP ，Blazek S ，Besler C ，Hartung P ，von Roeder M ，Petzold M ，Winkler S ，Höllriegel R ，Desch S ，Thiele H ，Lurz P ... -  《-》

Renal Denervation in the treatment of Resistant Hypertension.

Yap LB ，Balachandran K 《-》

Renal Sympathetic Denervation: A Viable Option for Treating Resistant Hypertension.

Accumulating evidence from mainly uncontrolled clinical studies with various types of ablation catheters have shown that renal denervation (RDN) can be applied safely and is effective in lowering blood pressure (BP) in patients with treatment-resistant hypertension. Sustained BP lowering has been documented up to 3 years. Furthermore, RDN has been associated with regression of target organ damage, such as left ventricular hypertrophy, arterial stiffness, and others. Several studies indicate potential benefit in other common clinical conditions associated with increased sympathetic tone including chronic kidney disease and heart failure. However, the recently published Symplicity HTN-3 study, the largest and most rigorously designed sham-controlled clinical trial, while confirming the safety of the procedure, failed to demonstrate a BP lowering effect beyond that of a sham procedure in patients with resistant hypertension. Efforts to unravel the reasons for the discrepant results from Symplicity HTN-3 have focused on a range of potential confounders including anatomical and procedural aspects. Indeed, data from post-hoc analyses indicate that sufficient RDN may not have been achieved in the majority of patients in Symplicity HTN-3. Furthermore, recent evidence from human postmortem and functional animal studies revealed new insights into the anatomical distribution of renal nerves and their accessibility by intravascular approaches. Initial results from recent clinical trials integrating these important findings indeed seem to confirm that RDN remains a viable option for the treatment of hypertension. Thorough further investigations will be key to determine the true potential of RDN in clinical conditions characterized by increased sympathetic drive.

Schlaich MP 《-》

Ambulatory heart rate reduction after catheter-based renal denervation in hypertensive patients not receiving anti-hypertensive medications: data from SPYRAL HTN-OFF MED, a randomized, sham-controlled, proof-of-concept trial.

The randomized sham-controlled SPYRAL HTN-OFF MED trial demonstrated that renal denervation (RDN) using a multi-electrode catheter lowers ambulatory blood pressure (BP) in non-medicated hypertensive patients. The current report describes the effects of RDN on heart rate (HR) in this population. Patients were enrolled with an office systolic BP (SBP) of ≥150 mmHg and <180 mmHg, office diastolic BP (DBP) of ≥90 mmHg, and a mean ambulatory SBP of ≥140 mmHg and <170 mmHg. Patients were drug naïve or removed from their anti-hypertensive medications. Eighty patients were randomized 1:1 to RDN or sham procedure. This post hoc analysis examines the effect at 3 months of RDN on HR and of high baseline 24-h HR on BP and HR changes. There was a significant reduction in 24-h HR at 3 months for the RDN group (-2.5 b.p.m.) compared with sham (-0.2 b.p.m.), P = 0.003 (analysis of covariance). Mean baseline-adjusted treatment differences were significantly different between groups at 3 months for average morning HR (-4.4 b.p.m., P = 0.046) and minimum morning HR (-3.0 b.p.m., P = 0.026). RDN patients with baseline 24-h HR above the median (73.5 b.p.m.) had significant reductions in average ambulatory SBP (-10.7 mmHg difference, P = 0.001) and DBP (-7.5 mmHg, P < 0.001), whereas BP changes in RDN patients with below-median HRs were not significant. Average and minimum morning HR were significantly reduced at 3 months for RDN compared with sham patients. A baseline 24-h HR above the median predicted greater BP reductions and may allow physicians to select patients likely to respond to the procedure.

Böhm M ，Mahfoud F ，Townsend RR ，Kandzari DE ，Pocock S ，Ukena C ，Weber MA ，Hoshide S ，Patel M ，Tyson CC ，Weil J ，Agdirlioglu T ，Fahy M ，Kario K ... -  《-》