1. Background
Catheter-based renal artery sympathetic denervation has emerged as a novel therapy for treatment of patients with drug-resistant hypertension. Initial studies were performed using a single electrode radiofrequency catheter, but recent advances in catheter design have allowed the development of multi-electrode systems that can deliver lesions with a pre-determined pattern. This study was designed to evaluate the safety and efficacy of the EnligHTN, a multi-electrode system.
2. Methods and results
We conducted the first-in-human, prospective, multicentre, non-randomized study in 46 patients (67% male, mean age 60 years, and mean baseline office blood pressure 176/96 mmHg) with drug-resistant hypertension. The primary efficacy objective was change in office blood pressure from baseline to 6 months. Safety measures included all adverse events with a focus on the renal artery and other vascular complications and changes in renal function. Renal artery denervation, using the EnligHTN system significantly reduced the office blood pressure from baseline to 1, 3, and 6 months by 28/10, 27/10 and 26/10 mmHg, respectively (P-0.0001). No acute renal artery injury or other serious vascular complications occurred. Small, non-clinically relevant, changes in average estimated glomerular filtration rate were reported from baseline (87 + 19 mL/min/1.73 m2) to 6 months post-procedure (82 + 20 mL/min/1.73 m2).
3. Conclusion
Renal sympathetic denervation, using the EnligHTN multi-electrode catheter results in a rapid and significant office blood pressure reduction that was sustained through 6 months. The EnligHTN system delivers a promising therapy for the treatment of drug-resistant hypertension.
4. Perspective
Use of renal sympathectomy for control of resistant hypertension dates back to the early 1930's. However, unselective sympathectomy was associated with significant morbidity and was discarded with the advent of newer generations of anti-hypertensive drugs. Interest in selective renal sympathectomy again picked up in the 1980s when preclinical research showed its value in various laboratory models of hypertension. This culminated in the first published trial of renal denervation therapy using single electrode catheter system in 2005.
Subsequent trials have demonstrated the noteworthy effects of renal denervation in resistant hypertension to be sustained over 6 months and more. Given the relative ease of the procedure and few procedural side effects, this therapy may have the potential to become the next milestone in the field of hypertension research and therapeutics.
The present trial introduces the use of a multi-electrode renal denervation catheter with an in-human prospective non-randomized study. This catheter has four geometrically arranged electrodes for simultaneous ablation at different sites. The putative advantages of a multi-electrode catheter may be: 1) reduced manipulation of the catheter in the renal arteries and 2) achieving more comprehensive renal denervation. This may help simplify the procedure further.
In this study, 46 patients of resistant hypertension (on ≥3 drugs) were taken up for the procedure. Renal arteries were selectively cannulated and the EnligHTN catheter (8 Fr compatible) placed proximal to the bifurcation of the renal arteries. Two sets of ablations (a total of 4–8 ablations/each ablation for 90 s) were administered. The second ablation was administered by pulling back the catheter by at least 1 cm and rotating by 45°. The energy generator had in-built power shut-off in case of excess energy deliverance. The catheter and sheath were removed sequentially and local site hemostasis achieved. Therefore the procedure was relatively straightforward with no great deviations from normal interventional protocols.
The trial was able to demonstrate an impressive 28/10 mm reduction in B.P as early as the first month. Given that the mean B.P at entry was 176/96 mm Hg, this was all the more striking. This B.P reduction appears to have sustained till 6 months of follow-up. However, only 13% (6) patients had a reduction in anti-hypertensive medications. Whether the investigators plan to follow up for a longer period before decreasing medications in the other patients remains to be seen. Non compliance to drugs or dietary indiscretion may have contributed to blunting of treatment effect. The SYMPLICITY 2 trial showed a 20% decrease in anti-hypertensive medications. Therefore, the potency of this therapy as a stand alone therapy remains unknown. Four patients had an increase in anti-hypertensive medications. A larger sample size may be able to clarify the significance of such outcomes.
Just like previous reports, this trial showed a reassuring absence of side effects related to the procedure. In particular, no renal artery damage was reported (dissections, aneurysms, flow limiting vasospasms). This is of special importance for interventionists starting out with this procedure.
In our opinion, renal nerve denervation using the EnligHTN multi-electrode renal denervation catheter appears to be a relatively safe and technically simple procedure. The effect on B.P reduction with this procedure appears to be significant, however, large randomized controlled trials are needed to assess efficacy with respect to cardiovascular outcomes, applicability to larger populations and evidence of re-innervation after this procedure. Use of this modality in less severe hypertensive populations will possibly be the next step in research which would ensure total freedom from all anti-hypertensive drugs.