Interventional procedure overview of percutaneous transluminal renal sympathetic denervation for resistant hypertension

Of the 9 papers, 5 papers focused on radiofrequency RDN (Pisano 2021; Townsend 2020; Mahfoud 2019; Zweiker 2016; Sharp 2016), 2 papers emphasised ultrasound RDN (Kario 2022; Azizi 2021), and 2 papers included both energy sources (Fengler 2019, 2021).

Studies were conducted in various countries and some data were collected in the UK including a UK registry.

Most studies had 3- or 6-month follow ups. The longest follow up was 84 months (I study included in Pisano 2021), followed by 4 years (Fengler 2021) and 3 years (Mahfoud 2019). The shortest follow-up duration was 2 months (Azizi 2021).

Of the 7 primary studies, there were 3 adequately powered, randomised trials. Two RCTs compared RDN using ultrasound with sham procedure (Kario 2022; Azizi 2021), and 1 randomised trial was a 3-arm trial comparing different techniques (USM-RDN, RFM-RDN and RFB-RDN; Fengler 2019). In terms of population, 2 randomised trials recruited patients from the US and Europe (Azizi 2021; Fengler 2019), and 1 trial included patients from Japan and South Korea (Kario 2022). For the 2 RCTs, between-group differences in office and 24-hour ambulatory systolic BP were found to be statistically significant in Azizi (2021) but not in Kario (2022). This was because of the unexpected, large BP reduction in the sham group in Kario (2022), highlighting study design issues (possibly caused by a significant number of unstable patients with uncontrolled hypertension and poor drug adherence enrolled in the study).

Outcomes might be affected by many factors, such as patient-specific characteristics, effects of comedication and adherence, surgeon's experience, and the technical aspects of the procedure.

RDN has evolved over the years and different renal denervation systems have been used. For radiofrequency RDN, the systems used include Symplicity Flex (single-electrode system), Symplicity Spyral (multi-electrode system), EnligHTN (multi-electrode basket), Vessix (balloon with bipolar radiofrequency electrodes), OneShot (balloon with spiral radiofrequency electrode). For ultrasound RDN, the system used is the Paradise system (ultrasound created heat/water-cooled balloon).

For radiofrequency RDN using different systems, Pisano (2021) found a greater decrease in office and 24-hour ambulatory BP in patients who had RDN using the multi-electrode catheter denervation system, having 4 ablations simultaneously delivered at the mid/distal segment of the renal artery, compared with the first-generation procedures (radiofrequency ablation via single-electrode catheter), with analysis factoring in the device type also reducing the heterogeneity among studies.

There was a lack of objective measure of medication adherence using blood or urine in most studies.

There might be a placebo effect on BP lowering after sham procedures or antihypertensive medications. The placebo effect might be greater with sham treatment than with medications.

Although Townsend (2020) included patients with uncontrolled hypertension, this meta-analysis of 50 trials explicitly reported renal artery damage after RDN. In this study, in addition to the 50 trials in the meta-analysis, authors also reviewed 11 individual cases of renal artery stenosis reported in 11 case reports. Combining case reports and clinical studies, renal artery damage after denervation with the Symplicity Flex catheter was reported in 37 patients, including 34 patients having stent implantation. Most events occurred within 1 year after the procedure. No cases of stenosis or dissection were reported involving the second-generation multi-electrode Symplicity Spyral system.

Studies that measure BP control and end-organ damage, with longer follow ups (possibly 5 to 10 years) and larger sample sizes, are needed.