First-in-Man Experience with a Novel Catheter-Based Renal Denervation System of Ultrasonic Ablation in Patients with Resistant Hypertension
Hypertension that is resistant to medical management (including at least three antihypertensive medications, including an anti-diuretic) is termed resistant hypertension. Sympathetic control of blood pressure is noted to have significant effect on blood pressure, and since the attempts of sympathectomy many decades ago, it has been posited that denervating this system may be an effective treatment for the severe hypertension these patients suffer with. There was considerable promise for percutaneous renal artery denervation with radiofrequency (RF) energy in initial non-US trials approximately 10 years ago, however the final US randomized trial failed to show benefit of the procedure compared to sham interventions (Simplicity HTN-3). Since that time, there has been a reappearance of efforts to evaluate renal nerve denervation (RDN) with new modalities.
The authors of manuscript describe their experience with RDN using use a 6-French TIVUS (Cardiosonic Ltd, Tel Aviv, Israel) catheter, which is an ultrasound-based catheter that can be placed in the renal artery without use of balloon occlusion. This first in man technique study is a prospective, multicenter, non-randomized, open-label clinical study consisting of three cohorts: Severe Resistant Hypertension (>160mmHg systolic in non-diabetic, >150mmHg in diabetic), Moderate Resistant Hypertension (>140mmHg systolic in non-diabetic, >130 in diabetic), and Failed RF Therapy (>150mmHg systolic in diabetic, >140mmHg in diabetic). Selection of patients was based on Office based blood pressures at 2 visits and 2-week home pressure monitoring, followed by 24-hour ambulatory blood pressure monitoring. If these were consistent with resistant hypertension, patients underwent screening renal angiography to ensure anatomical suitability, and then ultimately had RDN with either Unidirectional or Multidirectional catheters. Patients were followed for 6 months in clinic, which was the endpoint based on the commercial sponsor limitations. A total of 39 patients were enrolled, 20 of which had isolated systolic hypertension, and the remainder with combined systolic and diastolic hypertension. Two patients had prior RF denervation, now with recurrence of resistant hypertension. The authors found a mean reduction (-30mmHg systolic and -14mmHg diastolic) in blood pressure over the course of 6-month follow-up. The subsets of patients with the highest BP reduction included diabetics, those with combined systolic and diastolic hypertension and the patients who underwent multidirectional catheter denervation. There were no major adverse events and 6-month ultrasounds were normal in all patients.
Options for patients with primary resistant hypertension are limited, and although prior denervation-based treatments were derailed by the anticipated 2009 Simplicity-HTN3 trial’s failure to show benefit, the resurgence of multi-modality denervation studies are promising. This study demonstrated significant improvement in cohorts of patients, which can help future studies in patient selection. The limitation of only 6 months of study related follow-up was discussed by the authors, which needs more prolonged follow-up to ensure durability of the results. Additionally, although treatment benefit was shown in patients with recurrent disease despite prior denervation may be considered a source of bias, the finding that they responded could be considered a potential benefit that should be explored. Lack of this being a randomized, blinded study blinded is a limitation however this study alludes to safety and efficacy of this reiteration of RDN, providing a positive outlook for future trial development.
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Chernin G, Szwarcfiter I, Scheinert D, Blessing E, Diehm N, Dens J, Walton A, Verheye S, Shetty S, Jonas M. First-in-Man Experience with a Novel Catheter-Based Renal Denervation System of Ultrasonic Ablation in Patients with Resistant Hypertension. J Vasc Interv Radiol 2018; 29:1158-1166.
Kumar Madassery, MD
Assistant Professor, Vascular & Interventional Radiology
Director, Advanced Vascular & Interventional Radiology Fellowship
Rush University Medical Center, Chicago IL
Rush Oak Park Hospital, Oak Park IL
Twitter: @kmadass, @vir_rush