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Hypertension continues to be a prominent, avoidable factor contributing to major vascular issues on a global scale. Even with lifestyle adjustments and more aggressive medical treatments, maintaining optimal blood pressure levels remains challenging. This challenge has driven the emergence of device-oriented approaches to address hypertension. To assess the safety and efficacy of the Recor Paradise Ultrasound Renal Denervation System, the Circulatory System Devices Panel was convened by the US Food and Drug Administration (FDA). This manuscript provides a condensed overview of the information put forth by the sponsor and the FDA, along with an account of the considerations and conversations that took place during the meeting., (© 2024 Wiley Periodicals LLC.)

Background: Renal denervation with radiofrequency ablation has become an accepted treatment for drug-resistant hypertension. However, there is a continuing need to develop new catheters for high-accuracy, targeted ablation. We therefore developed a radiofrequency bipolar electrode for controlled, targeted ablation through Joule heating induction between 60 and 100 °C. The bipolar design can easily be assembled into a basket catheter for deployment inside the renal artery., Methods: Finite element modeling was used to determine the optimum catheter design to deliver a minimum ablation zone of 4 mm (W) × 10 mm (L) × 4 mm (H) within 60 s with a 500 kHz, 60 Vp-p signal, and 3 W maximum. The in silico model was validated with in vitro experiments using a thermochromic phantom tissue prepared with polyacrylamide gel and a thermochromic ink additive that permanently changes from pink to magenta when heated over 60 °C., Results: The in vitro ablation zone closely matched the size and shape of the simulated area. The new electrode design directs the current density towards the artery walls and tissue, reducing unwanted blood temperature increases by focusing energy on the ablation zone. In contrast, the basket catheter design does not block renal flow during renal denervation., Conclusions: This computational model of radiofrequency ablation can be used to estimate renal artery ablation zones for highly targeted renal denervation in patients with resistant hypertension. Furthermore, this innovative catheter has short ablation times and is one of the lowest power requirements of existing designs to perform the ablation., (© 2021. The Author(s).)

Background: Arterial hypertension is a common and life-threatening condition and poses a large global health burden. Device-based treatments have been developed as adjunctive or alternative therapy, to be used with or without antihypertensive medication for treating uncontrolled hypertension. The safety and feasibility of chemical renal denervation (RDN) using the Peregrine Catheter and alcohol were demonstrated in a first-in-man and open-label clinical trials, prompting the initiation of the ongoing TARGET BP OFF-MED and TARGET BP I trials., Design: The TARGET BP trials are randomized, blinded, sham-controlled trials designed to assess the safety and efficacy of alcohol-mediated RDN for the treatment of uncontrolled hypertension in the absence of antihypertensive medications (TARGET BP OFF-MED) or in addition to prescribed antihypertensive medications (TARGET BP I). Subjects with confirmed uncontrolled hypertension and suitable renal artery anatomy are randomized (1:1) to receive either RDN using the Peregrine Kit with alcohol (0.6 mL per renal artery) infused through the Peregrine Catheter or diagnostic renal angiography only (sham procedure). TARGET BP OFF-MED completed enrollment and randomized 96 subjects. TARGET BP I will randomize approximately 300 subjects and will transition to an open-label safety cohort of approximately 300 subjects receiving RDN once the primary efficacy endpoint of the Randomized Controlled Trial (RCT) cohort has been met. Primary endpoints are change in mean 24-hour ambulatory systolic blood pressure from baseline to 8 weeks (TARGET BP OFF-MED) and 3 months (TARGET BP I) post-procedure., Conclusion: The TARGET BP trials are the first large-scale, international, randomized trials aimed to investigate the safety and BP lowering efficacy of a novel RDN method, with perivascular alcohol delivery using the Peregrine Kit., (Copyright © 2021. Published by Elsevier Inc.)

Arterial hypertension is the most prevalent modifiable risk factor associated with cardiovascular morbidity and mortality. Although antihypertensive drugs are widely available, in many patients blood pressure control to guideline-recommended target values is not achieved. Several device-based approaches have been introduced to lower blood pressure; most of these strategies aim to modulate autonomic nervous system activity. Clinical trials have moved from including patients with resistant hypertension receiving intensive pharmacological treatment to including patients with mild-to-moderate hypertension in the presence or absence of antihypertensive medications. Renal sympathetic denervation is the most extensively investigated device-based therapy for hypertension, and randomized, sham-controlled trials have provided proof-of-principle data for its blood pressure-lowering efficacy. Unilateral electrical baroreflex activation, endovascular baroreflex amplification and pacemaker-mediated cardiac neuromodulation therapy have yielded promising results in observational trials, which need to be confirmed in larger, adequately powered, sham-controlled trials. Until further evidence becomes available, device-based therapy for hypertension should not be considered for routine treatment. However, when considering a device-based treatment for hypertension, the underlying pathophysiology in each patient has to be taken into consideration, and the procedural risks weighed against the cardiovascular risk attributable to the elevated blood pressure. This Review summarizes the pathophysiological rationale and the latest clinical evidence for device-based therapies for hypertension.

Objectives: The aim of this multicenter, open-label trial was to evaluate the safety and efficacy of alcohol-mediated renal denervation using a novel catheter system (the Peregrine System Infusion Catheter) for the infusion of dehydrated alcohol as a neurolytic agent into the renal periarterial space., Background: The number of hypertensive patients with uncontrolled blood pressure (BP) remains unacceptably low. The renal sympathetic nervous system has been identified as an attractive therapeutic target., Methods: Forty-five patients with uncontrolled hypertension on ≥3 antihypertensive medications underwent bilateral renal denervation using the Peregrine Catheter with 0.6 ml alcohol infused per renal artery., Results: All patients were treated as intended. Mean 24-h ambulatory BP reduction at 6 months versus baseline was -11 mm Hg (95% confidence interval [CI]: -15 to -7 mm Hg) for systolic BP and -7 mm Hg (95% CI: -9 to -4 mm Hg) for diastolic BP (p < 0.001 for both). Office systolic BP was reduced by -18/-10 mm Hg (95% CI: -25 to -12/-13 to -6 mm Hg) at 6 months. Antihypertensive medications were reduced in 23% and increased in 5% of patients at 6 months. Adherence to the antihypertensive regimen remained stable over time. The primary safety endpoint, defined as the absence of periprocedural major vascular complications, major bleeding, acute kidney injury, or death within 1 month, was met in 96% of patients (95% CI: 85% to 99%). Two patients had major adverse events of periprocedural access-site pseudoaneurysms, with major bleeding in one. There were no deaths or instances of myocardial infarction, stroke, transient ischemic attack, or renal artery stenosis. Transient microleaks were noted in 42% and 49% of the left and right main renal arteries, respectively. There were 2 cases of minor vessel dissection that resolved without treatment., Conclusions: Primary results from this trial suggest that alcohol-mediated renal denervation using the Peregrine Catheter safely reduces blood pressure and as such may represent a novel approach for the treatment of hypertension., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to investigate bipolar radiofrequency renal denervation in patients with hypertension not receiving medications at baseline., Background: A blood pressure-reducing effect of renal denervation has been difficult to isolate in clinical investigations., Methods: REDUCE HTN: REINFORCE (Renal Denervation Using the Vessix Renal Denervation System for the Treatment of Hypertension) was a randomized, sham-controlled multicenter trial. Patients with office systolic blood pressure (SBP) of 150 to 180 mm Hg and average 24-h ambulatory SBP of 135 to 170 mm Hg after medication washout underwent bipolar radiofrequency renal denervation or a sham procedure. The planned outcome was 8-week change in 24-h ambulatory SBP. Enrollment was terminated for apparent futility before a sufficient sample for powered efficacy comparisons was enrolled. Safety assessments included all-cause death, renal failure, severe hypotension or syncope, hypertensive crisis, and renal artery stenosis., Results: Baseline 24-h blood pressure was 148.3 ± 10.9/85.7 ± 9.1 mm Hg for the denervation group (n = 34, mean age 58.5 ± 10.1 years, 47% women) and 149.1 ± 7.2/86.4 ± 9.8 mm Hg for the control group (n = 17, mean age 58.2 ± 9.8 years, 24% women). At 8 weeks, mean 24-h SBP reductions for the renal denervation and control groups were -5.3 mm Hg (95% confidence interval [CI]: -8.8 to -1.8 mm Hg) and -8.5 mm Hg (95% CI: -13.3 to -3.8 mm Hg), respectively (difference 3.3 mm Hg; 95% CI: -2.8 to 9.3 mm Hg; p = 0.30). Antihypertensive medications could then be added. By 6 months, decreases in SBP were greater for the denervation group, yielding between-group differences of -7.2 mm Hg (95% CI: -15.2 to 0.8 mm Hg; p = 0.08), -9.7 mm Hg (95% CI: -17.7 to -1.7 mm Hg; p = 0.02), and -11.4 mm Hg (95% CI: -19.2 to -3.7 mm Hg; p < 0.01) for 24-h, daytime ambulatory, and office measurements, respectively. Through 12 months, 1 patient (renal denervation group) had a hypertensive urgency requiring immediate management, and 1 experienced progression of renal artery stenosis., Conclusions: Future studies of radiofrequency renal denervation must anticipate delayed treatment effects. (Renal Denervation Using the Vessix Renal Denervation System for the Treatment of Hypertension [REDUCE HTN: REINFORCE]; NCT02392351)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Competing Interests: T. Chang is a site co-investigator for controlling and lowering blood pressure with the MobiusHD (CALM-2), a trial which is sponsored by Vascular Dynamics, Inc.

Purpose: Although percutaneous catheter-based ablation of renal sympathetic nerve fibers has been used in the treatment of patients with resistant hypertension, a recent phase III study did not confirm its efficacy. In this study, we developed a novel laparoscopic renal denervation system and evaluated its safety and initial feasibility using an animal model., Materials and Methods: A novel surgical instrument that uses a smart algorithm with temperature-monitoring feedback was developed. We used 4 male pigs (6 weeks old, weighing approximately 45 kg each) to evaluate the safety and efficacy of the laparoscopic renal denervation system. We performed immunohistochemical staining analysis after renal denervation using various tip temperatures and over various durations through an open approach., Results: When the temperature of the outer wall of the renal artery was maintained at 90℃ for 180 seconds, the artery was completely denervated without damaging its inner layer, as evaluated using Masson's trichrome staining. When the temperature ranged from 70℃ to 90℃ and the duration ranged from 90 to 420 seconds, partial or complete denervation without significant vessel injury was confirmed with anti- growth-associated protein 43 and anti-S100 staining., Conclusions: This animal study confirmed the safety and feasibility of the novel laparoscopic renal denervation system. A safe and effective protocol was developed with ablation at a constant tissue temperature of 70℃ to 90℃ within 180 seconds. However, further developments are necessary before its clinical use., Competing Interests: CONFLICTS OF INTEREST: This novel laparoscopic renal denervation system was invented by Chang Wook Jeong and Sung-Min Park., (© The Korean Urological Association, 2020.)

Arterial hypertension is associated with increased cardiovascular morbidity and mortality. Although blood pressure-lowering therapies significantly reduce the risk of major cardiovascular events, blood pressure control remains unsatisfactorily low. Several device-based antihypertensive therapies have been investigated in patients with treatment-resistant hypertension and in patients unable or unwilling to adhere to antihypertensive medication. As the field of device-based therapies is subject to constant change, this review aims at providing an up-to-date overview of different device-based approaches for the treatment of hypertension. These approaches target the sympathetic nervous system (renal denervation, baroreflex amplification therapy, baroreflex activation therapy, and carotid body ablation) or alter mechanical arterial properties by creating an iliac arteriovenous fistula. Notably, the use of all of these treatment options is not recommended for the routine treatment of hypertension by current guidelines but should be investigated in the context of controlled clinical studies., (© American Journal of Hypertension, Ltd 2019. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Aims: Pulmonary arterial hypertension is a devastating disease characterised by pulmonary vascular remodelling and right heart failure. Radio-frequency pulmonary artery denervation (PDN) has improved pulmonary haemodynamics in preclinical and early clinical studies; however, denervation depth is limited. High-frequency non-focused ultrasound can deliver energy to the vessel adventitia, sparing the intima and media. We therefore aimed to investigate the feasibility, safety and efficacy of ultrasound PDN., Methods and Results: Histological examination demonstrated that innervation of human pulmonary arteries is predominantly sympathetic (71%), with >40% of nerves at a depth of >4 mm. Finite element analysis of ultrasound energy distribution and ex vivo studies demonstrated generation of temperatures >47ºC to a depth of 10 mm. In domestic swine, PDN reduced mean pulmonary artery pressure induced by thromboxane A2 in comparison to sham. No adverse events were observed up to 95 days. Histological examination identified structural and immunohistological changes of nerves in PDN-treated animals, with sparing of the intima and media and reduced tyrosine hydroxylase staining 95 days post procedure, indicating persistent alteration of the structure of sympathetic nerves., Conclusions: Ultrasound PDN is safe and effective in the preclinical setting, with energy delivery to a depth that would permit targeting sympathetic nerves in humans.

Patients with isolated systolic hypertension (ISH) are thought to show a diminished blood pressure (BP)-lowering effect after renal sympathetic denervation (RDN). This conclusion is mostly derived from unipolar radiofrequency catheter ablation studies. Limited data for newer RDN technologies exist. We used data from the RADIOSOUND-HTN (Three-Arm Randomized Trial of Different Renal Denervation Devices and Techniques in Patients With Resistant Hypertension) comparing 3 different RDN approaches to investigate a possible interaction between ISH and RDN response. One hundred twenty patients were stratified by having ISH or combined systolic-diastolic hypertension (CH). Of these, 39 underwent radiofrequency ablation of the renal main arteries, 39 combined radiofrequency ablation of the main and branch arteries, and 42 were treated with ultrasound-based ablation of the main renal artery. Patients with ISH (n=61) were older and had lower systolic and diastolic BP on ambulatory measurement (ambulatory BP measurement) at baseline in comparison to CH (n=59). At 3 months, patients with ISH showed a less pronounced BP-lowering effect of RDN as compared to patients with CH (daytime average -5.9±11.8 versus -13.3±11.7 mm Hg, P=0.001). This difference was significant for radiofrequency ablation of the renal main arteries and ultrasound-based ablation of the main renal artery treatment but did not reach significance in the radiofrequency ablation of the main and branch arteries group. After adjustment for baseline BP values and age, there was no significant difference in BP reduction between ISH and CH. Using unadjusted BP values, RDN seems to be more effective in CH than in ISH. However, adjusting for baseline BP values revealed similar BP reduction in ISH and CH patients, irrespective of the RDN treatment used. The value of ISH as predictor for successful RDN might have been overestimated in the past. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT02920034.

Background:  Primary palmar hyperhidrosis (PPH) is featured by aberrantly perspiration of the hands, which may bring a lot of inconvenience to patient's daily life and work. The purpose of this study is to summarize the clinical effect of needlescopic video-assisted thoracic bilateral T4 sympathicotomy for the treatment of PPH., Patients and Methods:  Between January 2009 and March 2014, 200 patients received needlescopic video-assisted thoracic bilateral T4 sympathicotomy. We, respectively, took two 5-mm incisions in the third intercostal space on the anterior axillary line and in the fifth intercostal space on the middle axillary line. After collapsing left lung, needlescopic exploration was the first step to determine the targeted sympathetic chain through the third intercostal space. Electric coagulation hook was inserted from another port to cut T4 sympathetic chain and the bypassing nerve fibers for 2 to 3 cm along the surface of the fourth rib. Right thoracic cavity was also administered the same procedure. The palmar temperature was recorded before and after sympathicotomy. The symptom improvement, operative complications, patients' recovery, and satisfaction were evaluated., Finding:  One hundred and ninety-seven patients uneventfully received two 5-mm port bilateral sympathicotomy, and another 3 patients with extensive pleural adhesions completed the surgery through enlarging the third intercostal incision to 2 cm without conversion to open surgery. All operative procedures were completed in 15 to 35 minutes. The hospital stay was 2 to 4 days. The palmar temperature increased by 2.0 ± 0.5°C, and hyperhidrosis immediately disappeared in both hands after surgery. The efficacy rate was 100%. The postoperative complications such as hemorrhage, hemopneumothorax, bradycardia, or Horner's syndrome had no occurrence. During 6 to 60 months follow-up, mild compensatory sweating of buttock, back, and thigh occurred in 30 patients (15%) at 2 to 5 days after surgery and gradually disappeared at postoperative 15 to 30 days or longer time. All patients were greatly satisfied with the effect with better confidence and quality of life. Until now, no recurrent palmar hyperhidrosis happened., Conclusion:  Needlescopic video-assisted thoracic bilateral T4 sympathicotomy could reach an excellent and immediate result of treating PPH. It is a safe, convenient, and minimally invasive method appropriate for wide clinical use., Competing Interests: The authors report no conflict of interest., (Georg Thieme Verlag KG Stuttgart · New York.)

Despite availability of effective drugs for hypertension therapy, significant numbers of hypertensive patients fail to achieve recommended blood pressure levels on ≥3 antihypertensive drugs of different classes. These individuals have a high prevalence of adverse cardiovascular events and are defined as having resistant hypertension (RHT) although nonadherence to prescribed antihypertensive medications is common in patients with apparent RHT. Furthermore, apparent and true RHT often display increased sympathetic activity. Based on these findings, technology was developed to treat RHT by suppressing sympathetic activity with electrical stimulation of the carotid baroreflex and catheter-based renal denervation (RDN). Over the last 15 years, experimental and clinical studies have provided better understanding of the physiological mechanisms that account for blood pressure lowering with baroreflex activation and RDN and, in so doing, have provided insight into which patients in this heterogeneous hypertensive population are most likely to respond favorably to these device-based therapies. Experimental studies have also played a role in modifying device technology after early clinical trials failed to meet key endpoints for safety and efficacy. At the same time, these studies have exposed potential differences between baroreflex activation and RDN and common challenges that will likely impact antihypertensive treatment and clinical outcomes in patients with RHT. In this review, we emphasize physiological studies that provide mechanistic insights into blood pressure lowering with baroreflex activation and RDN in the context of progression of clinical studies, which are now at a critical point in determining their fate in RHT management.

Background: Resistant hypertension and renal sympathetic hyperactivity are closely linked, and catheter-based renal denervation (RDN) is regarded as a new treatment strategy. However, the acute changes in vascular morphology and relaxation function have yet to be evaluated, and these may be important for the efficacy and safety of the procedure. In this study, we explored these questions by conventional temperature-controlled cardiac radiofrequency catheter-based RDN in a pig model., Methods: Six mini-pigs were randomly divided into the renal denervation (RDN) group (n = 3) and the Sham-RDN group (n = 3). Animals in the RDN group underwent unilateral radiofrequency ablation, and those in the Sham-RDN group underwent the same procedure except for the ablation. The pigs were examined by angiography pre- and post-RDN and were euthanized immediately thereafter. Renal arteries were processed for histological and molecular biology analyses as well as for in vitro vascular tension testing., Results: Compared with the Sham-RDN group, the RDN caused vascular intima and media injury, renal nerve vacuolization, mild collagen fiber hyperplasia and elastic fiber cleavage (all p < 0.05). The RDN group also significantly exhibited nitric oxide synthase pathway inhibition and decreased endothelium-independent vascular relaxation function Compared to the Sham-RDN group (all p < 0.05)., Conclusions: In this porcine model, renal artery denervation led to vascular wall injury and endothelial dysfunction in the acute phase, which negatively affected vascular relaxation function. Thus, this process may be detrimental to the prognosis and progress of hypertension patients.

Objectives: To assess the clinical efficacy of renal artery denervation (RAD) in our center and to compare the efficacy of two different radiofrequency (RF) systems., Background: Several systems are available for RF renal denervation. Whether there is a difference in clinical efficacy among various systems remains unknown., Methods: Renal artery denervation was performed on 43 patients with resistant hypertension using either the single electrode Symplicity Flex (n = 20) or the multi-electrode EnligHTN system (n = 23). Median post-procedural follow-up was 32.93 months. The primary outcome was post-procedural change in office blood pressure (BP) within 1 year (short-term follow-up). Secondary outcomes were change in office BP between 1 and 4 years (long-term follow-up) and the difference in office BP reduction between the two systems at each follow-up period., Results: For the total cohort, mean baseline office BP (systolic/diastolic) was 174/94 mmHg. At follow-up, mean changes in office BP from baseline were -19.70/-11.86 mmHg (P < 0.001) and -21.90/-13.94 mmHg (P < 0.001) for short-term and long-term follow-up, respectively. The differences in office BP reduction between Symplicity and EnligHTN groups were 8.96/1.23 mmHg (P = 0.42 for systolic BP, P = 0.83 for diastolic BP) and 9.56/7.68 mmHg (P = 0.14 for systolic BP, P = 0.07 for diastolic BP) for short-term and long-term follow-up, respectively., Conclusions: In our cohort, there was a clinically significant office BP reduction after RAD, which persisted up to 4 years. No significant difference in office BP reduction between the two systems was found., (© 2018 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals, Inc.)

Background: Both radiofrequency and ultrasound endovascular renal sympathetic denervation (RDN) have proven clinical efficacy for the treatment of hypertension. We performed a head-to-head comparison of these technologies., Methods: Patients with resistant hypertension were randomly assigned in a 1:1:1 manner to receive either treatment with (1) radiofrequency RDN of the main renal arteries; (2) radiofrequency RDN of the main renal arteries, side branches, and accessories; or (3) an endovascular ultrasound-based RDN of the main renal artery. The primary end point was change in systolic daytime ambulatory blood pressure at 3 months., Results: Between June 2015 and June 2018, 120 patients were enrolled (mean age, 64±9 years±SD; mean daytime blood pressure, 153/86±12/13 mm Hg). Of these, 39 were randomly assigned to radiofrequency main renal artery ablation, 39 to combined radiofrequency ablation of the main artery and branches, and 42 to ultrasound-based treatment. Baseline daytime blood pressure, clinical characteristics, and treatment were well balanced between the groups. At 3 months, systolic daytime ambulatory blood pressure decreased by 9.5±12.3 mm Hg ( P<0.001) in the whole cohort. Although blood pressure was significantly more reduced in the ultrasound ablation group than in the radiofrequency ablation group of the main renal artery (-13.2±13.7 versus -6.5±10.3 mm Hg; mean difference, -6.7 mm Hg; global P=0.038 by ANOVA, adjusted P=0.043), no significant difference was found between the radiofrequency ablation groups (-8.3±11.7 mm Hg for additional side branch ablation; mean difference, -1.8 mm Hg; adjusted P>0.99). Similarly, the blood pressure reduction was not found to be significantly different between the ultrasound and the side branch ablation groups. Frequencies of blood pressure response ≥5 mm Hg were not significantly different (global P=0.77)., Conclusions: In patients with resistant hypertension, endovascular ultrasound-based RDN was found to be superior to radiofrequency ablation of the main renal arteries only, whereas a combined approach of radiofrequency ablation of the main arteries, accessories, and side branches was not., Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02920034.

Backgroud: Primary focal hyperhidrosis affects between 1 to 4% of the general population, with a higher prevalence in teenagers and young adults. The condition is characterized by excessive sweating in 1 or more body part, most often the palms, face, armpits and soles. This condition causes a significant negative impact on patient's quality of life. The pathophysiology of focal hyperhidrosis is believed to be due to excessive sympathetic stimulation, and videothoracoscopic sympathectomy is a recognized form of treatment. The aim of this study is to evaluate the post-operative quality of life of patients who underwent thoracoscopic sympathectomy., Materials and Methods: This is a retrospective study of fifty-four patients with primary focal hyperhidrosis submitted to bilateral thoracoscopic thoracic sympathectomy at the Center of Cardiothoracic Surgery of Casa de Saúde da Boavista, between January 2011 and December 2014. The Quality of Life questionnaire and the Hyperhidrosis Severity Scale questionnaire were used to evaluate the quality of life in the pre-operative period and 3 months after surgery. Further to this, data was collected regarding medium-term follow-up by telephone. All patients underwent general anesthesia and had bilateral video-assisted thoracoscopic resection of the sympathetic chain., Results: The majority of patients are females 59.3% (32). The mean age is 30.8 ± 7.70 (between 16 and 49 years). Prior to surgery, 85% of the patients had severe hyperhidrosis. 79.6% of respondents stated that general discomfort was promoted by the condition, with the Funcional-Social domain being the most affected aspect of their life (61.1%). The rates of peri-operative complications and major post-operative complications were null, and minor complications were 5.5%. After 3 months, improvement in patient's quality of life and satisfaction level were of 100% and 96.3% respectively, however compensatory hyperhidrosis was observed in 53.7% of patients. 57.3% of the patients reported significant improvements in the Funcional-Social domain. Medium-term follow-up (mean=6 years) allowed for the evaluation of 31 patients (57.4% of the population), of whom 77.4% maintained compensatory hyperhidrosis. 93.5% reported to be highly satisfied with the surgical results and claimed to have improved their quality of life by 93.5%. 94% and 94.4% respectively of the patients evaluated in the medium term follow-up and after 3 months and in the medium term follow-up, recommend the surgery., Conclusion: Sympathectomy by video-assisted thoracoscopic surgery (VATS) is an effective and viable therapeutic option for primary focal hyperhidrosis patients. Despite compensatory hyperhidrosis being observed at time, this procedure produces very satisfactory results particularly in regard to the patient's post-operative quality of life.

This study evaluated the subacute morphologic alterations in renal artery wall and renal nerves in response to catheter-based renal denervation (RDN) in sheep and also compared the efficiency of single-point and multiple-point ablation catheters. Effect of each ablation catheter approved for the clinical use (Symplicity Flex(TM), Medtronic, Inc., or EnligHTN(TM), St. Jude Medical, INC.) was compared to intact contralateral renal artery in 12 sheep by histopathology and immunohistochemistry evaluation after a 10-day period post-RDN procedure. The safety was verified by extensive evaluation of kidney morphology. Vascular wall lesions and nerve injuries were more pronounced in those animals treated with multi-point EnligHTN catheter when compared with animals treated with single-point Symplicity Flex catheter. However, neither RDN procedure led to complete renal nerve ablation. Both systems, tested in the present study, provided only incomplete renal nerve ablation in sheep. Moreover, no appreciable progression of the nerve disintegration in subacute phase post-RDN procedure was observed. This study further supports the notion that the effectiveness remains fully dependent on anatomical inter-individual variability of the sympathetic nerve plexus accompanying the renal artery. Therefore, new systems providing deeper penetrance to targeted perivascular structure would be more efficient.

Renal sympathetic hyperactivity is critically involved in hypertension pathophysiology; renal denervation (RDN) presents a novel strategy for treatment of resistant hypertension cases. This study assessed effects of two RDN systems to detect acute intravascular, vascular and peri-vascular changes in the renal artery, and renal nerve alterations, in the sheep. The procedures using a single-point or multi-point ablation catheters, Symplicity Flex(TM), Medtronic versus EnligHTN(TM), St. Jude Medical were compared; the intact contralateral kidneys served as controls. Histopathological and immunohistochemical assessments were performed 48 h after RDN procedures; the kidney and suprarenal gland morphology was also evaluated. Special staining methods were applied for histologic analysis, to adequately score the injury of renal artery and adjacent renal nerves. These were more pronounced in the animals treated with the multi-point compared with the single-point catheter. However, neither RDN procedure led to complete renal nerve ablation. Forty-eight hours after the procedure no significant changes in plasma and renal tissue catecholamines were detected. The morphologic changes elicited by application of both RDN systems appeared to be dependent on individual anatomical variability of renal nerves in the sheep. Similar variability in humans may limit the therapeutic effectiveness of RDN procedures used in patients with resistant hypertension.

Background: Single-electrode ablation of the main renal artery for renal sympathetic denervation showed mixed blood pressure (BP)-lowering effects. Further improvement of the technique seems crucial to optimize effectiveness of the procedure. Because sympathetic nerve fibers are closer to the lumen in the distal part of the renal artery, treatment of the distal main artery and its branches has been shown to reduce variability in treatment effects in preclinical studies and a recent randomized trial. Whether this optimized technique improves clinical outcomes remains uncertain. We report a 2-center experience of main renal artery and combined main renal artery plus branches renal denervation in patients with resistant hypertension using a multielectrode catheter., Methods and Results: Twenty-five patients with therapy-resistant hypertension underwent renal sympathetic denervation with combined main renal artery and renal branch ablation and were compared to matched controls undergoing an ablation of the main renal artery only. BP change was assessed by ambulatory measurement at baseline and after 3 months. At baseline, BP was balanced between the groups. After 3 months, BP changed significantly in the combined ablation group (systolic/diastolic 24-hour mean and daytime mean BP -8.5±9.8/-7.0±10.7 and -9.4±9.8/-7.1±13.5 mm Hg, P <0.001/0.003 and <0.001/0.016, respectively), but not in patients with main artery treatment (-3.5±11.1/-2.0±7.6 and -2.8±10.9/-1.8±7.7 mm Hg, P =0.19/0.20 and 0.19/0.24, respectively). Systolic daytime BP was significantly more reduced in patients with combined ablation than in patients with main artery ablation ( P =0.033)., Conclusions: Combined ablation of the main renal artery and branches appears to improve BP-lowering efficacy and should be further investigated., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background and Aims: Catheter-based renal denervation for the treatment of drug-resistant hypertension has been intensively investigated in recent years. To date, only limited data have been published using multi-electrode radiofrequency ablation systems that can deliver lesions with a pre-determined pattern. This study was designed to evaluate the safety and performance of the second generation EnligHTN™ Renal Denervation System., Methods: This first-in-human, prospective, multi-center, non-randomized study included 39 patients (62% male, mean age 63 years, and mean baseline office blood pressure 174/93 mmHg) with drug-resistant hypertension. The primary safety and performance objectives were to characterize, from baseline to 6 months post procedure, the rate of serious procedural and device related adverse events, as adjudicated by an independent Clinical Events Committee, and the reduction of office systolic blood pressure., Results: Renal artery denervation, using the second generation EnligHTN multi-electrode system significantly reduced office blood pressure from baseline to 1, 3, 6, 12, 18 and 24 months by 19/7, 26/9, 25/7, 23/7, 25/8 and 27/9 mmHg, respectively (p ≤ 0.0005). No serious device or procedure related adverse events affecting the renal arteries or renal function occurred through 24 months of follow-up., Conclusions: Renal sympathetic denervation using the second generation EnligHTN Renal Denervation System resulted in safe, rapid, and significant mean office blood pressure reduction that was sustained through 24 months. Future studies will need to address the utility of this system against an appropriate sham based comparator., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

We describe a new technique of performing sympathectomy with a new device. A single skin incision 3 mm long was made in the armpit. The device enables complete resection of the sympathetic segment through a single skin incision, whereas sympathectomy is limited by the use of the conventional needle technique. Even if sympathetic nerves and blood vessels were overlapping, separation of the two organs was performed safely. This device increases the possibility of planning surgical procedures for patients with difficult anatomies., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Aims: Trials of transcatheter renal artery denervation (RDN) have failed to show consistent antihypertensive efficacy. Procedural factors and limitations of radiofrequency ablation can lead to incomplete denervation. The aim of the study was to show that non-contact microwave catheter ablation could produce deep circumferential perivascular heating while avoiding injury to the renal artery intima and media., Methods and Results: A novel microwave catheter was designed and tested in a renal artery model consisting of layers of phantom materials embedded with a thermochromic liquid crystal sheet, colour range 50-78°C. Ablations were performed at 140 W for 180 sec and 120 W for 210 sec, delivering 25,200 J with renal arterial flow at 0.5 L/min and 0.1 L/min. Transcatheter microwave ablations 100-160 W for 180 sec were then performed in the renal arteries of five sheep. In vitro, ablations at 140 W and 0.5 L/min flow produced circumferential lesions 5.9±0.2 mm deep and 19.2±1.5 mm long with subendothelial sparing depth of 1.0±0.1 mm. In vivo, transcatheter microwave ablation was feasible with no collateral visceral thermal injury. There was histological evidence of preferential outer media and adventitial ablation., Conclusions: Transcatheter microwave ablation for RDN appears feasible and provides a heating pattern that may enable more complete denervation while sparing the renal arterial intima and media.

Aims: The blood pressure-lowering effect of percutaneous renal denervation (RDN) is controversial. The success of RDN may be device-dependent. We sought to compare the efficacy of RDN by chemical neurolysis using alcohol (Peregrine System Infusion Catheter; Ablative Solutions, Inc., Menlo Park, CA, USA) to RDN by radiofrequency (RF) ablation with the single-electrode RF catheter (Symplicity Flex; Medtronic, Minneapolis, MN, USA) in a porcine model., Methods and Results: This was a prospective, randomised, blinded study. Pigs were assigned to undergo bilateral RF ablation or chemical neurolysis. Primary endpoints were ablation depth and renal tissue norepinephrine (NE) concentrations at three-month follow-up. Twelve pigs underwent RF ablation (n=4) or chemical neurolysis by infusion of 0.3 mL (n=4) or 0.6 mL (n=4) alcohol. Ninety days after RF ablation and chemical neurolysis with 0.3 mL and 0.6 mL of alcohol, mean maximal tissue injury depth was 3.9±1.2 mm, 6.6±1.7 mm and 8.2±2.2 mm, respectively (p<0.001 for either dose of alcohol vs. RF ablation). Compared with historical controls, median renal tissue NE concentration reductions were 66%, 78% and 83% after RF ablation and chemical neurolysis using 0.3 mL and 0.6 mL alcohol, respectively (p=0.107 for chemical neurolysis vs. RF ablation). Mean total ablation area was significantly greater in both (0.3 mL and 0.6 mL) alcohol groups (p=0.0001 for both) than the RF ablation group (30.8±13.7 mm2, 41.6±12.4 mm2 and 11.0±7.5 mm2, respectively)., Conclusions: RDN is more effective using chemical neurolysis than single-electrode RF ablation. Our findings suggest that the efficacy of RDN may be device-dependent.

Background: There are many ways to treat focal hyperhidrosis, including surgeries for palmar and axillary hyperhidrosis. However, doctors and patients tend to be reluctant to perform surgery for plantar hyperhidrosis due to misconceptions and prejudices about surgical treatment. In addition, few studies have reported the outcome of surgeries for plantar hyperhidrosis. Therefore, the objective of this study was to determine the outcome (early and late postoperative satisfaction, complication, compensatory hyperhidrosis, recurrence rate, and efficiency) of surgical treatment for plantar hyperhidrosis., Materials and Methods: From August 2014 to October 2015, lumbar sympathetic block (LSB) was performed in 82 patients with plantar hyperhidrosis using clipping method. Limited video-assisted LSB was performed using 5 mm ligamax-clip or 3 mm horizontal-clip after identifying L3-4 sympathetic ganglion through finger-touch and endoscopic vision., Results: Of the 82 patients, 45 were male and 37 were female. Their mean age was 26.38 years (range, 14-51 years). Mean follow-up time was 6.60 ± 3.56 months. Mean early postoperative satisfaction score was 9.6 on the 10th day postoperative evaluation. At more than 1 month later, the mean late postoperative satisfaction score was 9.2. There was no significant difference in early postoperative satisfaction score between clipping level L3 and L4/5. However, late postoperative satisfaction score was significantly better in the L3 group than that in the L4/5 group. Patient's age and body mass index did not affect the satisfaction score. However, male patients and patients who had history of hyperhidrosis operation showed higher satisfaction score than others., Conclusion: Limited video-assisted LSB using clip provided good results with minimal complications and low compensatory hidrosis, contrary to the prejudice toward it. Therefore, surgical treatment is recommended for plantar hyperhidrosis.

Endoscopic thoracic sympathectomy (ETS) is an effective treatment of primary hyperhidrosis of the face, upper extremities, and axillae. The major limitation is the side effect of compensatory sweating severe enough that patients request reversal in up to 10% of cases. When ETS is performed by cutting the sympathetic chain, reversal requires nerve grafting. However, for ETS done with clips, reversal is a simple thoracoscopic outpatient procedure of removing the clips. Subsequent reversal of the sympathectomy, ie, nerve regeneration, is successful in many cases. However, follow-up is short. Factors contributing to success rates require further study., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Left ventricular (LV) hypertrophy and diastolic dysfunction predict long-term cardiovascular events. We evaluated whether multielectrode renal denervation (RDN) can provide beneficial cardiac adaptations in patients with resistant hypertension and LV hypertrophy long term at 24 months. Seventeen patients with true drug-resistant hypertension (age: 57±9 years, 11 men, body mass index: 33.79±5.49 kg m - 2 , office blood pressure (BP): 183±20/97±18 mm Hg and ambulatory BP: 152±16/86±15 mm Hg receiving 4.5 anti-hypertensive drugs per day) and LV hypertrophy underwent multielectrode RDN (EnligHTNTM, St Jude Medical). At baseline, LV mass index averaged 141.1±16.8 g m - 2 (58.4±7.8 g m -2.7 ) and mitral lateral E/E' 14.7±6.2. At 6, 12 and 24 months after RDN, the LV mass/body surface area (LV mass per height 2.7 ) reduced significantly by 9.1% (8.8%), 11.3% (10.5%) and 15.5% (14.1%), respectively; and the mitral lateral E/E' reduced significantly by 14.0%, 15.3% and 29.7%, respectively. At 24 months after RDN, majority (70.6%) of the patients showed regression of LV hypertrophy of at least one level; the proportion of patients with concentric LV hypertrophy had dropped by 47.1% from baseline; and the proportion of patients with office systolic BP level of ⩾160 mm Hg had dropped by 76.5% from baseline. No statistically significant association was observed between the changes in office BP and the changes in LV mass index or diastolic function. In patients with drug-resistant hypertension and LV hypertrophy, multielectrode RDN can contribute to significant and sustained improvements of diastolic dysfunction and attenuation of LV mass indices long term at 24 months.

Background: Traditional endoscopic thoracic sympathicotomy is usually performed through an axillary incision with 5-mm thoracoscope under general anesthesia with endotrachea intubation. Nonintubated transareolar single-port thoracic sympathicotomy with a needle scope has rarely been attempted. The objective of this study is to evaluate the feasibility and safety of this minimally invasive technique in managing primary palmar hyperhidrosis (PPH)., Methods: From May 2012 to May 2014, a total of 85 male patients with severe PPH underwent transareolar single-port thoracic sympathicotomy by use of a 2-mm needle scope under total intravenous anesthesia without endotrachea intubation., Results: All procedures were successfully performed with a mean operating time of 13.5 min. The palms of all patients became dry and warm as soon as the sympathetic chain was cut off. There were no sore throat, and all the patients regained consciousness rapidly after surgery. Eighty-two patients (96.5 %) were discharged from the hospital on the first postoperative day. The postoperative complications were minor, and no patients developed Horner's syndrome. At 6 months postoperatively, there is no obvious surgical scar on the chest wall, and none of the patients complained about postoperative pain. Compensatory sweating appeared in 31 patients. No recurrent symptoms were observed in our study. One-year follow-up revealed an excellent cosmetic result and degree of satisfaction., Conclusions: Nonintubated transareolar single-port needlescopic thoracic sympathicotomy is a safe, effective and minimally invasive therapeutic procedure, which can be performed in routine clinical practice for male PPH patients.

Renal denervation (RDN) has emerged as a potential device-based treatment for resistant hypertension. The authors present their experience of the use of catheter-based RDN as part of routine clinical care in two specialist hypertension clinics. Thirty-four patients with uncontrolled hypertension underwent RDN. All patients had ambulatory blood pressure (BP) monitoring and directly observed medication administration prior to the procedure to exclude white-coat hypertension and nonadherence, respectively. Overall, there was a significant change in clinic systolic BP of -15.1 mm Hg (95% confidence interval, -23.4 to -6.8; P=.001) and clinic diastolic BP of -6.2 mm Hg (95% confidence interval, -11.5 to -0.9; P=.02) 6 months postprocedure, and a nonsignificant change in daytime ambulatory BP of -5.4/-2.9 mm Hg. Eighteen patients (51.4%) showed a significant reduction in their clinic systolic BP (≥10 mm Hg) and 16 (47%) had a significant reduction in their daytime ambulatory systolic BP (≥5 mm Hg) at 6 months., (© 2015 Wiley Periodicals, Inc.)

Objectives: This study evaluated the first clinical use of a new endovascular approach to renal denervation, using chemical neurolysis, via periadventitial infusion of dehydrated alcohol (ethanol) to perform "perivascular" renal artery sympathetic denervation., Background: Renal denervation remains a promising technology for the treatment of hypertension and other disorders., Methods: A novel 3-needle delivery device (Peregrine System Infusion Catheter, Ablative Solutions, Inc., Kalamazoo, Michigan) was introduced into the renal arteries of 18 subjects with refractory hypertension. Microdoses of alcohol were infused bilaterally via the 3 needles into to the adventitial space (0.30 ml/artery, 37 arteries). Renal artery angiography was performed at the time of the procedure and at 6 months (n = 16). The primary safety endpoints were complications associated with the catheter insertion and delivery of the neurolytic agent or any major vascular access complications. The secondary performance endpoint was a reduction in office-based systolic blood pressure at 6 months compared with baseline., Results: Procedural success was achieved in 100% of subjects (N = 18) and arteries (N = 37). There were no study-related adverse clinical events at follow-up. One death of a subject was recorded but determined by the investigator and an independent medical monitor to be non-study related. There were no angiographic observations of renal artery stenosis, aneurysms, or other renal artery abnormalities at 6 months (32 renal arteries). Sixteen of the 18 subjects had a 6-month follow-up. The mean office systolic blood pressure decreased from 175 ± 17 mm Hg to 151 ± 26 mm Hg (-24 mm Hg). There was an average reduction of antihypertensive medications from 3.4 (baseline) to 2.0 per subject at 6 months., Conclusions: Chemical renal denervation using the infusion of very low doses of alcohol directly into the adventitial space appears to be feasible and safe. This approach may be a promising alternative approach to perform catheter-based renal denervation. These results need to be confirmed in larger scale clinical studies., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Efficacy of radiofrequency ablation (RFA) of prevertebral sympathetic nodes, concern- ing the arterial pressure lowering in 36 patients, suffering hypertonic disease and coex- istent heart diseases, was analyzed. In 12 mo after RFA a systolic arterial pressure lowering at average throughout the group by (3.24 ± 1.15) kPa, or (24.3 ± 8.6) mm Hg, diastolic arterial pressure--by (1.51 ± 0.45) kPa, or (11.3 ± 3.4) mm Hg was noted. RFA of prevertebral sympathetic nodes have had promoted a stable lowering of arterial pressure in patients, suffering chronic hypersympathicotony.

Objective: Natural orifice transluminal endoscopic surgery (NOTES) has recently become a hot spot in the field of minimally invasive surgery. But, most of the procedures are still in the early stages of development and limited to animal experiments. Transareolar endoscopic surgery could work as a viable intermediate step before thoracic NOTES. Under intravenous anesthesia without endotracheal intubation, transareolar endoscopic thoracic sympathectomy (ETS) with a flexible endoscope has rarely been attempted. The objective of this study is to evaluate the feasibility and safety of this novel minimally invasive technique in managing primary palmar hyperhidrosis (PPH)., Methods: From June 2012 to July 2014, a total of 58 male patients with severe PPH underwent transareolar ETS by use of a flexible endoscope. Under intravenous anesthesia without endotracheal intubation, a flexible endoscope was introduced through the incision on the edge of the areola into the thoracic cavity. The thoracic sympathetic chain was ablated at the level of the fourth rib., Results: All procedures were successfully performed with a mean operating time of 33.6 ± 8.3 min. All patients regained consciousness rapidly and none of them complained about sore throat after surgery. There were no operative mortality and conversion to open procedure. The symptoms of all patients disappeared as soon as the sympathetic chain was cut off. Fifty six patients (96.6%) were discharged from the hospital on the first postoperative day. The postoperative complications were minor, and no patients developed Horner's syndrome. At 3 months postoperatively, there was no obvious surgical scar on the chest wall, and none of the patients complained about postoperative pain. Compensatory hyperhidrosis (CH) appeared in 19 patients. No recurrent symptoms were observed in our study. One year follow-up revealed an excellent cosmetic result and degree of satisfaction., Conclusion: Nonintubated transareolar ETS with a flexible endoscope is a safe, effective and minimally invasive therapeutic procedure, which has the possible advantages of thoracic NOTES and can be performed in routine clinical practice for male PPH patients.

Purpose: Endoscopic thoracic sympathectomy/sympathotomy for the treatment of palmar hyperhidrosis is generally performed by either cutting or clamping the sympathetic chain. However, it remains unclear as to which of these methods is more effective and has fewer side effects. This study was conducted to compare the effects of sympathotomy by cutting or clamping at T3 on two outcomes--postoperative palmar sweating and compensatory sweating; it also evaluated postoperative patient satisfaction., Methods: The participants were among 289 patients who underwent bilateral sympathotomy at T3 for palmar hyperhidrosis. These patients were sent questionnaires by mail to assess their self-reported degree of postoperative palmar sweating and compensatory sweating, as well as their level of satisfaction. Of the 92 patients who responded to the questionnaire, 54 had undergone sympathotomy by cutting (cutting group) and 38 by clamping (clamping group)., Results: The degree of postoperative palmar sweating was significantly lower in the cutting group than in the clamping group. However, compensatory sweating was significantly more severe in the cutting group than in the clamping group. No significant difference was observed in the degree of patient satisfaction between the groups., Conclusions: Sympathotomy by clamping at T3 was less effective in reducing the primary symptom of postoperative palmar sweating, but induced less compensatory sweating than did sympathotomy by cutting at T3. However, both methods were similar with regard to patient satisfaction. The degree of postoperative palmar sweating and the severity of compensatory sweating were inversely correlated with the degree of patient satisfaction.

Clinical application efficacy of a navigation systems with a three-dimension reconstruction of aorta and renal arteries, while performance of their catheteric radiofrequency sympathetic denervation, was studied. Application of intraoperative navigation in the patients, operated on for refractory arterial hypertension, improves postoperatively the arterial pressure contol significantly. Positive clinical effect secures during 18 mo as minimum. The complications absence witnesses the method safety and expediency of its wide introduction into the practice.

Aims: Circumferential ablation of renal sympathetic nerves using catheter-based ultrasound energy was studied in a preclinical in vivo model. The aim was to investigate the benefit of cooling the arterial wall and the extent of renal nerve injury based on histopathology, and to correlate the injury with kidney norepinephrine levels., Methods and Results: Computer simulations of the ultrasound transducer within the cooling balloon demonstrated a circumferentially uniform heating profile. In vivo characterisation was performed in 10 normotensive pigs. Nine were treated bilaterally with ultrasound and survived for seven days (n=8) or were sacrificed acutely (n=1). Acutely, TTC staining of the renal arteries treated with ultrasound energy in the presence of cooling demonstrated viable tissue consistent with preservation of the arterial medial layer. Histological studies demonstrated no endothelial injury and minimal to no injury to the media of the renal arterial wall at seven days. Overall, circumferential nerve damage with up to 76% of nerve bundles affected within 7.5 mm of the arterial lumen was observed. Kidney norepinephrine (NEPI) levels were significantly reduced in all animals compared to a non-treated control animal (n=1) and correlated with the degree of nerve damage. A greater reduction in NEPI and a greater percentage of affected nerves was observed in arteries treated with two or three bilateral ultrasound emissions., Conclusions: Catheter-based ultrasound delivered within a cooling balloon is effective at targeting the majority of the renal nerves circumferentially, resulting in significantly decreased kidney NEPI levels without damaging the arterial wall in a porcine model.

Objectives: The aims of this study were to examine human renal arteries and to accurately characterize their sympathetic innervation and location using CD-56 immunohistochemistry stains to highlight Neural Cell Adhesion Molecules (N-CAM)., Background: Porcine models have often formed the basis for design of denervation technology, with only a limited number of human studies available to detail the complex microarray of renal sympathetic nerves., Methods: Post-mortem renal arteries (N = 14) were harvested and prepared into three sections (proximal, mid, and distal), and then stained using Hematoxylin and Eosin, followed by immunohistochemistry to characterize the expression of CD-56 renal neural tissue. Digital micro calipers were then used to measure the nerve distances and locations within the vessels., Results: (i) Approximately 77% of nerves are located between 0.5 and 2.5 mm from the tunica intima layer, with 22.5% occurring in the 2.5-5.0 mm range, (ii) nerve bundles occur in 3-dimensional arborized arrays, (iii) the nerve bundles are evenly distributed throughout the proximal and distal vessel in this human study. Thickness of vessel wall correlated with proximity of the nerve bundles (r = 0.74, P < 0.01), and nerve bundle thickness (r = 0.62, P = 0.04). The larger the internal and external diameters and areas of the vessel were, the further the distance to the nearest nerve bundles were (r = 0.752, P =<0.01)., Conclusions: In human renal arteries with larger diameters and thicker vessel parenchyma, the innervation is found further from the lumen, and the nerves increase in thickness. This has implications for catheter and system design, as well as depth and duration of energy required for effective ablations. Effective percutaneous transluminal denervation procedures in this population would need to be circumferential rather than interrupted, and to mediate tissue damage to depths beyond 2.5 mm from the tunica intima., (© 2015 Wiley Periodicals, Inc.)

Background/purpose: We update the pre-clinical and early clinical results using a novel endovascular approach, to perform chemical renal denervation, via peri-adventitial injection of micro-doses of dehydrated alcohol (ethanol-EtOH)., Methods/materials: A novel, three-needle delivery device (Peregrine™) was used to denervate the renal arteries of adult swine (n = 17) and in a first-in-man feasibility study (n = 18). In the pre-clinical testing EtOH was infused bilaterally with one infusion per renal artery into to the perivascular space, using EtOH doses of 0.3 ml/artery (n = 8), and 0.6 ml/artery (n = 9), and with saline sham control (0.4 ml/artery n = 3). Renal parenchymal norepinephrine (NE) concentration (performed blindly), and safety were the primary endpoints. Data from the first-in-man study (n = 18) to evaluate device performance, safety and peri-procedural pain are reported., Results: In the pre-clinical testing renal function was unchanged at 3-month follow-up. Angiography at 90 days (n = 34 arteries) demonstrated normal appearing renal arteries, unchanged from baseline, and without stenosis or other abnormalities. The reductions in mean renal parenchymal NE reductions at 3 months were 68% and 88% at doses of 0.3 and 0.6 ml, respectively (p < 0.001 vs. controls). In the first-in-man study, there was 100% device success, no complications, a mean treatment time of 4.3 ± 3 minutes/artery, and minimal or no patient discomfort during treatment. Angiography at 6-months showed no evidence of renal artery stenosis, and evidence of a reduction of blood pressure from baseline., Conclusion: Perivascular RDN using micro-doses of alcohol is a promising alternative to energy-based systems to achieve dose-dependent, predictable, safe and essentially painless renal denervation. Further clinical evaluation is warranted., Summary: (For annotated table of contents) This paper describes the preclinical results, in a porcine model, and the early first-in-man results, using the Peregrine™ chemical renal denervation catheter to perform renal sympathetic denervation using micro-doses of alcohol., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Sympathetic nervous system hyperactivity plays a role in development and progression of hypertension. While renal denervation employing radiofrequency devices has been used therapeutically in treating severe hypertension with alternate results in adults, few data are available regarding children. We treated a 6-year-old girl affected by Turner syndrome presenting severe hypertension and an episode of stroke, in spite of treatment with four antihypertensive drugs, with sympathetic ablation. The Simplicity device (Medtronic, Minneapolis, USA) was adapted to the smaller vessels, allowing a tailored approach. After 3 and 6 months of treatment, and β-blocker discontinuation, blood pressure values were set between the 90th and 95th centiles for sex and age, and normalised at 12 months. We confirm that renal denervation can be used to treat severe hypertension in children; miniaturisation of catheter and tailoring the procedure for small vessels allowed a safe approach. Progressive improvement of blood pressure had a satisfactory clinical impact., (2015 BMJ Publishing Group Ltd.)

Background: Sympathetic interruption offers excellent control of hyperhidrosis and facial blushing (FB), but some patients have side effects prompting a wish to reverse the procedure. Reversal when the chain has been cut is challenging, whereas reversal when the chain has been clipped is straightforward. The peripheral nerves regenerate; however, little is known about the regeneration of the sympathetic chain after clip removal. We reviewed our results with reversal of sympathetic interruption through removal of clips., Methods: An institutional review board-approved retrospective review of patients treated for hyperhidrosis and FB from November 2004 to March 2014 was performed. We analyzed those patients undergoing sympathetic interruption with clips (N = 82)., Results: Eight patients (10%) requested and underwent reversal of the procedure between 12 days and 5.8 years (median = 73.5 days) after the initial procedure. Compensatory sweating was the most frequent complaint (n = 6), and excessive palmar dryness was second (n = 3), the latter occurring in patients without primary palmar hyperhidrosis. The interval between clip removal and follow-up ranged from 2 days to 4.5 years (median = 141 days). Five of 8 patients thus far have had their symptoms reversed through removal of clips (Table 1)., Conclusions: The percentage of patients requesting reversal of sympathectomy is significant and appears to most commonly result from compensatory sweating (CS); however, excessive palmar dryness also occurs in those without primary palmar hyperhidrosis. It appears that the best results with reversal are obtained when the clips are removed early after placement. We counsel our patients that ideally clips should be removed within 2 weeks for reversal., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Aims: Renal denervation is a potential new treatment therapy for resistant hypertension. However, anatomic vascular variations might complicate the procedure and increase complications. A radial approach offers easier renal artery access and is associated with a decreased risk of vascular access complications., Methods and Results: We describe the first-in-man use of a radial access ultrasound-based renal denervation device (Radiance™; ReCor, Palo Alto, CA, USA) in two patients with therapy-resistant hypertension. Both procedures were uneventful and resulted in significant blood pressure reductions at three-month follow-up (mean office blood pressure drop [-40/-29 mmHg]; mean ambulatory blood pressure drop [-11/-8 mmHg])., Conclusions: Radial access renal artery denervation using the Radiance catheter appears to be safe and effective and should be considered an alternative option in patients referred for renal denervation.

Aims: The Paradise Ultrasound Renal Denervation System is a next-generation catheter-based device which was used to investigate whether the target ablation area can be controlled by changing ultrasound energy and duration to optimise nerve injury while preventing damage to the arterial wall., Methods and Results: Five ultrasound doses were tested in a thermal gel model. Catheter-based ultrasound denervation was performed in 15 swine (29 renal arteries) to evaluate five different doses in vivo, and animals were euthanised at seven days for histopathologic assessment. In the gel model, the peak temperature was highest in the low power-long duration (LP-LD) dose, followed by the mid-low power-mid duration (MLP-MD) dose and the mid-high power-short duration (MHP-SD) dose, and lowest in the mid power-short duration (MP-SD) dose and the high power-ultra short duration (HP-USD) dose. In the animal study, total ablation area was significantly greater in the LP-LD group, followed by the MLP-MD group, and it was least in the HP-USD, MP-SD and MHP-SD groups (p=0.02). Maximum distance was significantly greater in the LP-LD group, followed by the MLP-MD group, the MHP-SD group, and the HP-USD group, and shortest in the MP-SD group (p=0.007). The short spare distance was not different among the five groups (p=0.38). Renal artery damage was minimal, while preserving significant nerve damage in all groups., Conclusions: The Paradise Ultrasound Renal Denervation System is a controllable system where total ablation area and depth of ablation can be optimised by changing ultrasound power and duration while sparing renal arterial tissue damage but allowing sufficient peri-arterial nerve damage.

Aims: Renal denervation has emerged as a treatment option for patients with drug-resistant hypertension. This study was designed to assess the safety and effectiveness of the OneShotª Renal Denervation System., Methods and Results: RAPID is a prospective, multicentre, single-arm study which enrolled 50 patients at 11 clinical sites in Europe and New Zealand. Eligible patients had an office systolic blood pressure (SBP) ≥160 mmHg and were on a stable regimen of ≥3 antihypertensive medications including a diuretic. The primary safety endpoints were acute procedural safety at discharge and chronic procedural safety at six months. The primary effectiveness endpoint was the rate of office SBP reduction ≥10 mmHg at six months compared to baseline. While not a predefined endpoint, change in 24-hour ambulatory BP was evaluated. The mean baseline office SBP and diastolic BP measurements were 181.6±20.8 and 95.5±15.5 mmHg, respectively. Patients were on a mean of 5.1 antihypertensive medications at baseline. The mean office BP decreased by -20/-8 mmHg (p<0.0001/p=0.0002), and -22/-8 mmHg (p<0.0001/p=0.0014), from baseline to six and 12 months, respectively. The 24-hour ABPM was also significantly reduced by -11/-6 mmHg at six months compared to baseline (p=0.0085/p=0.037). There were no serious adverse events (SAE) at discharge related to groin and vascular access complication or renal artery injury or SAE/adverse device effects at six months., Conclusions: The results of the RAPID study demonstrate safe delivery of RF energy by the OneShot Renal Denervation System for renal sympathetic denervation and sustained efficacy, as evidenced by a significant reduction in office and 24-hour ABPM for six months, which was sustained up to 12 months. ClinicalTrials.gov Identifier: NCT01520506.

Aims: A bipolar multi-electrode 7 Fr-compatible balloon-catheter radiofrequency (RF) renal denervation system (Vessix™ Renal Denervation System; Boston Scientific, Marlborough, MA, USA) was evaluated for safety in domestic swine., Methods and Results: Renal arteries of 27 swine received overlapping treatments proximally/single treatments distally to mimic balloon overlap clinically. Each histopathology cohort (30, 90, 180 days) had four RF-treated and three sham-treated (no RF energy delivered) animals, with the response of artery/surrounding nerves to bilateral treatment examined (42 arteries). Scanning electron microscopy of the renal artery flow surface for endothelialisation was performed in six additional pigs (three at each of 30 and 90 days: 12 arteries) following unilateral whole artery treatment with proximal overlap: RF one side, sham the other side. Power was ~1 watt, treatment duration 30 seconds, target temperature 68°C. Renal histology and assessment for off-target injury was performed in all 27 swine. Renal artery thermal injury was transmural and segmental involving <10% to >90% of the circumference (typically 30-60%) with segmental neointimal hyperplasia exceeding shams but haemodynamically trivial (maximum stenosis 17.7%). Healing of necrotic arterial media was by replacement fibrosis. Overlying nerves also became fibrotic. Endothelialisation was focally incomplete at 30 days but confluent at 90 days. No off-target injury occurred outside the renal arteries., Conclusions: Safety was demonstrated.

Background: Transluminal renal sympathetic denervation (RDN) has been shown to reduce blood pressure (BP) in patients with treatment-resistant hypertension., Methods: We assessed the effect of multi-electrode RDN on short-term BP variability indexes in resistant hypertensives. Thirty-one patients with drug-resistant uncontrolled hypertension, participants in the EnligHTN I study, underwent ambulatory BP measurements at baseline and 6months after RDN using the EnligHTN ablation catheter (St. Jude Medical). Twelve resistant hypertensives matched for office BP served as control group., Results: At 6months post-RDN, office BP and 24-hour BP were reduced by 25.6/10.3mmHg and by 10.2/6mmHg (p<0.001 for all cases), respectively. No significant changes were observed 6months post-RDN in standard short-term BP variability indexes including 24-hour systolic and diastolic average real variability. The rates of systolic and diastolic 24-hour BP variation were decreased 6months after RDN, (from 0.40/0.30 to 0.34/0.24, p=0.030/0.006, respectively), especially in the responders group (n=23, 74.2%). No significant differences in BP and BP variability parameters in the control group were detected. ROC analysis revealed an area under the curve for prediction of response to RDN by systolic time rate of 66.8% (95% CI: 46.7% to 87%; p=0.16) and by diastolic time rate of 76.1% (95% CI: 58.2% to 93.9%; p=0.030)., Conclusions: Although standard BP variability indexes remained unchanged, the rate of systolic and diastolic BP variation was significantly decreased 6months after RDN in patients with drug-resistant hypertension. These novel indexes might also be useful as predictors of response., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)