Technical advance in silico and in vitro development of a new bipolar radiofrequency ablation device for renal denervation.

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.

Renal denervation in a patient with a highly tortuous renal artery using a guide extension catheter: a case report.

BACKGROUND: Catheter-based renal denervation (RDN) has been introduced to treat resistant hypertension. Although the technology of RDN has been largely improved, denervation of tortuous renal arteries remains challenging. CASE PRESENTATION: This is a case report of a 49-year-old man with drug resistant hypertension. The patient was selected for RDN after ruling out possible causes of secondary hypertension. Computed tomography angiography showed a highly tortuous left renal artery. An Iberis multielectrode ablation catheter failed to reach the target vessel with a regular guiding catheter. A 5-French extension catheter was introduced into the proximal segment of the main left renal artery to provide extra support force, which enabled successful ablation of the highly tortuous left renal artery. His ambulatory blood pressure was significantly decreased at 1 month follow-up. CONCLUSIONS: It is feasible and effective to use a guide extension catheter for denervation of highly tortuous renal arteries. The present study provides a useful method to ablate tortuous and angled renal arteries and branches.

Catheter-based alcohol-mediated renal denervation for the treatment of uncontrolled hypertension: design of two sham-controlled, randomized, blinded trials in the absence (TARGET BP OFF-MED) and presence (TARGET BP I) of antihypertensive medications.

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.

VATS sympathectomy for hyperhidrosis.

Excessive sweating in the hands, feet, and armpits is a difficult problem for people who suffer from it and is an increasingly frequent reason for consulting a thoracic surgeon. The existing medical treatments are only palliative, so primary hyperhidrosis is a definite indication for thoracic sympathectomy. This video tutorial shows in detail the 2-port videothoracoscopic surgical technique performed by our surgical team.

Device-based therapies for arterial hypertension.

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.

The REDUCE HTN: REINFORCE: Randomized, Sham-Controlled Trial of Bipolar Radiofrequency Renal Denervation for the Treatment of Hypertension.

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).

Alcohol-Mediated Renal Denervation Using the Peregrine System Infusion Catheter for Treatment of 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.

Animal model evaluation of a novel renal denervation system for future laparoscopic treatment of resistant hypertension.

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.

The Current Status of Devices for the Treatment of Resistant Hypertension.

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.

Minilaparoscopic lumbar sympathectomy with 3 mm instruments for plantar hyperhidrosis / Simpatectomia lombar endoscópica com microinstrumental de 3 mm para hiperidrose plantar

Abstract Severe palmoplantar hyperhidrosis affects about 1.5-2.8% of the general population. Plantar hyperhidrosis (PHH) is related to foot odor, cold feet, skin lesions and infections, and even instability when walking. Endoscopic Lumbar Sympathectomy (ELS) is the treatment of choice for this condition. However, few surgeons have used this technique over the past 20 years because of its technical difficulty. Two and 3 mm instruments, rather than the standard 5 mm instruments, have been used to improve the results of several standard laparoscopic procedures. Use of these minilaparoscopic instruments to perform ELS so far has not yet been published. We describe a technique for ELS using minilaparocopic instruments, which we have used for our last 70 cases and has become our standard technique. The aim of this study is to demonstrate the feasibility of this technique and its advantages compared to the conventional technique.

Resumo A hiperidrose palmoplantar grave afeta cerca de 1,5-2,8% da população geral. A hiperidrose plantar está relacionada a odor dos pés, pés frios, lesões cutâneas, infecções, e até instabilidade da marcha. A simpatectomia lombar endoscópica (endoscopic lumbar sympathectomy, ELS) é o tratamento de escolha para essa condição; entretanto, tem sido utilizada por poucos cirurgiões nos últimos 20 anos, devido à sua dificuldade técnica. Instrumentos de 2 e 3 mm em vez de 5 mm vêm sendo utilizados para melhorar os resultados de vários procedimentos laparoscópicos padrão. O uso desses instrumentos para realizar ELS ainda não foi descrito. Descrevemos a técnica para ELS usando microinstrumentos, a qual vem sendo usada para os nossos últimos 70 casos, pois passou a ser nosso procedimento padrão. O objetivo deste estudo é apresentar a experiência com essa modificação técnica, assinalando as vantagens em relação à técnica tradicional.

Renal Denervation in Isolated Systolic Hypertension Using Different Catheter Techniques and Technologies.

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.

[A retrospective study on the quality of life of patients with primary focal hyperhidrosis that underwent a video-assisted thoracoscopic sympathectomy]. / Avaliação do Impacto na Qualidade de Vida de Pacientes Diagnosticados com Hiperdrose Primária Submetidos a Simpaticectomia Torácica por Vídeo-Toracoscopia.

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.

Introdução: A Hiperidose Focal Primária afeta entre 1 a 4% da população, principalmente adolescentes e jovens- -adultos. É um distúrbio secundário a um excesso de estimulação simpática caracterizado por sudorese excessiva que pode envolver as mãos, a face, as axilas e os pés, representando um importante impacto negativo na qualidade de vida dos pacientes. A simpaticectomia vídeotoracoscópica é uma forma reconhecida de tratamento desta patologia. Este estudo tem como principal objetivo avaliar a qualidade de vida pós-cirúrgica dos pacientes submetidos a simpaticectomia por cirurgia toracoscópica videoassistida. Material e Métodos: Estudo retrospetivo de cinquenta e quatro pacientes com hiperidrose focal primária submetidos a simpaticectomia torácica por videotoracoscopia bilateral, na Clínica de Cirurgia Cardiotorácica da Casa de Saúde da Boavista, entre Janeiro de 2011 e Dezembro de 2014. Foram utilizados o questionário Quality of Life e a Hiperhidrosis Severity Scale na avaliação da qualidade de vida no pré-operatório e nos 3 meses após a cirurgia, bem como, a recolha de dados via telefónica num follow up a médio prazo. Todos os pacientes foram submetidos a anestesia geral e a técnica cirúrgica usada foi a secção da cadeia simpática bilateralmente por cirurgia vídeo-toracoscópica. Resultados: A maioria dos pacientes é do sexo feminino 59,2% (32). A idade média de idades é de 30,8 ± 7,70 (entre 16 e 49 anos). Antes da cirurgia, 85% dos pacientes apresentavam hiperidrose severa. O grau de desconforto geral promovido pela hiperidrose é de 79,6% sendo o domínio mais afetado o Funcional-Social (61,1%). Não houve complicações perioperatórias e pós-operatórias major. A taxa de complicações minor foi de 5,5%. Após 3 meses, obteve- -se um índice geral de 100% de melhoria na qualidade de vida dos pacientes e um grau de satisfação positivo de 96,3% apesar do aparecimento de hiperhidrose compensatória em 57,3% dos pacientes. O Domínio que apresentou melhorias significativas foi o Funcional-Social, em 55,5% dos pacientes. O follow up a médio prazo (média de 6 anos) permitiu avaliar 31 pacientes (57,4% da população) dos quais 77,4% mantém hiperhidrose compensatória. 93,5% Refere satisfação elevada com o resultado cirúrgico tendo melhorado a sua qualidade de vida em 93,5%. Dos pacientes avaliados no follow up a 3 meses e a médio prazo, 94,4% e 94,0% recomendam a cirurgia, respetivamente. Conclusão: A simpaticectomia por cirurgia toracoscópica videoassistida é uma opção terapêutica eficaz e viável da hiperidrose focal primária. Apesar da incidência de hiperidrose compensatória, é um procedimento bastante satisfatório no que respeita à qualidade de vida da grande maioria dos pacientes submetidos a este tipo de cirurgia.

Pulmonary artery denervation using catheter-based ultrasonic energy.

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.

Device-Based Neuromodulation for Resistant Hypertension Therapy.

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.

Acute changes in morphology and renal vascular relaxation function after renal denervation using temperature-controlled radiofrequency catheter.

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.

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

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.

Needlescopic Video-Assisted Thoracic Bilateral T4 Sympathicotomy for the Treatment of Primary Palmar Hyperhidrosis: An Analysis of 200 Cases.

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.

Comparison of two different radiofrequency ablation systems for renal artery denervation: Evaluation of short-term and long-term follow up.

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.

Evaluation of later morphologic alterations in renal artery wall and renal nerves in response to catheter-based renal denervation in sheep: comparison of the single-point and multiple-point ablation catheters.

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.