Renal Denervation (RDN) has emerged over the last decade as a third pillar in the treatment of arterial hypertension, alongside pharmacotherapy and lifestyle modifications. Mechanistically, it reduces central sympathetic overactivation, a process also relevant to heart failure. In this mini-review, we summarize the development of RDN for heart failure, discuss the current evidence supporting its effects, and provide an outlook on future developments.

The field of renal denervation remains challenged by the inability to confirm successful ablation of the targeted renal sympathetic nerves. The availability of technology to measure regional blood flow in real-time makes sympathetic control of the renal vasculature a logical end point to assess effective renal denervation, but autoregulatory mechanisms mask effects on mean renal blood flow. We hypothesized that renal sympathetic vasomotion, a novel marker of rhythmic sympathetic control, reflects successive rounds of catheter-based radiofrequency renal denervation.

To test this, 10 pigs underwent unilateral surgical renal denervation, recovered for at least 7 days, and then underwent 4 successive rounds of catheter-based radiofrequency denervation of the contralateral kidney. Bilateral renal blood flow velocity and abdominal aortic pressure were measured before and after ablations to calculate renal vasomotion.

Before catheter-based denervation, the renal vasomotion profiles of the innervated and surgically denervated kidneys differed significantly (P<0.005). Ablation of the largest renal branch artery reduced renal sympathetic vasomotion by 52%. Ablation of the remaining renal branch arteries reduced sympathetic vasomotion by 95% from baseline and eliminated the statistical differences between surgically and catheter-denervated kidneys. Two additional rounds of catheter denervation of the main renal artery did not consistently decrease the renal sympathetic vasomotion magnitude any further.

These results indicate that renal sympathetic vasomotion could provide intraprocedural feedback for interventionalists performing catheter-based renal denervation and thereby improve the efficacy, safety, and consistency of this antihypertensive intervention.

Endovascular renal denervation (RDN) is a catheter-based, procedural therapy for the treatment of hypertension that was approved by the US Food and Drug Administration (FDA) in November 2023. Early studies suggest that endovascular RDN reduces blood pressure (BP) in patients with hypertension. However, BP response to RDN is highly variable, optimal patient selection remains uncertain, and the procedure's high cost remains a significant challenge. The purpose of this review is to comprehensively examine the literature regarding the mechanism by which endovascular RDN reduces BP and the safety and effectiveness of RDN, and to discuss key considerations for selecting appropriate patients for endovascular RDN. Relevant studies in the field were identified from PubMed using search terms including 'renal denervation' and 'renal denervation for hypertension.' In conclusion, clinical trials have demonstrated a statistically significant BP-lowering effect of endovascular RDN, which based on multiple trials with long-term follow-up, appears to persist over several years with low complication rates. More research is needed to understand which patients benefit most from endovascular RDN and to evaluate the long-term outcomes, including the impact of endovascular RDN on cardiovascular events.

Catheter-based total renal denervation (TRDN) has recently gained FDA approval to lower blood pressure in patients with treatment-resistant hypertension. Current TRDN technologies indiscriminately destroy efferent (sympathetic) and afferent (sensory) renal nerves. However, preclinical studies suggest that the beneficial effects of TRDN may be due to ablation of afferent, rather than efferent, renal nerves. We developed a novel method for chemical ablation of afferent renal nerves by periaxonal application of capsaicin which has been employed in mouse and rat models of hypertension. In certain rodent models afferent-specific renal denervation (ARDN) has been shown to lower arterial pressure to the same degree as TRDN. The objective of the present study was to develop a catheter-based method for ARDN in a large animal model with the long-term goal of translating this treatment to humans. We tested the feasibility of using the Peregrine™ catheter infusion system, currently used to perform TRDN in humans by injection of ethanol, to perform catheter-based afferent renal denervation in sheep by periaxonal application of capsaicin.

Castrated, adult, male, Friesen sheep underwent Sham RDN (saline, n = 2), TRDN (ethanol, n = 4), or ARDN (capsaicin, n = 4) with the Peregrine™ catheter before termination > 2 weeks after the procedure. Denervation of renal efferents was verified by measurement of renal cortical norepinephrine (NE) content and anti-tyrosine hydroxylase (TH) staining; denervation of renal afferents was verified with anti-calcitonin gene-related peptide (CGRP) staining.

There was a significant decrease in TH + and CGRP + fibers in TRDN kidneys and in CGRP + but not TH + fibers in ARDN kidneys. TRDN significantly reduced renal cortical norepinephrine (NE) content by 89% while ARDN had similar NE content to Sham RDN kidneys.

This study establishes the feasibility of performing catheter-based afferent renal denervation in a large animal model. Furthermore, this study provides a translational model to evaluate catheter-based ARDN as a potential treatment for hypertension.

Studies have shown that renal denervation (RDN) can lower blood pressure (BP) in patients with refractory hypertension, but issues such as renal sympathetic nerve reinnervation and suboptimal BP reduction remain unresolved. In this study, we identified the aorticorenal ganglion (ARG) in canines by observing ambulatory BP responses following electrical stimulation of the ARG. We injected cholera toxin subunit B combined with Alexa Fluor™ 555, a nerve tracer, into the identified ARG and confirmed its innervation of the renal artery and kidney by observing fluorescence in adjacent tissues. Twelve experimental canines were divided equally into an intervention group, which received ARG ablation using 95% ethanol, and a sham control group, which received normal saline. Our results demonstrated that ARG ablation significantly reduced systolic, diastolic, and mean arterial pressures, with minimal impact on heart rate. Additionally, ARG ablation lowered plasma and renal cortex norepinephrine levels, and reduced tyrosine hydroxylase expression in the renal cortex. No adverse events were observed during the 3-month follow-up period. These findings suggest that the ARG may serve as a novel target for RDN and could offer a therapeutic alternative for patients who do not respond to or experience elevated BP after RDN.

The objective of this study was to evaluate the effects of renal denervation (RDN) on cardiac remodeling, cardiac function, and cardiovascular (CV) neurohormones in heart failure patients with reduced ejection fraction (HFrEF).

We searched PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI), identifying 6 randomized controlled trials (RCTs) and 9 single-arm studies, totaling 352 participants. Meta-analyses for RCTs and single-arm studies were conducted using STATA 17 software and the metafor package in R, respectively.

In RCTs, RDN significantly reduced left ventricular end-diastolic diameter (LVEDD) (weighted mean difference [WMD] = -3.55 mm, 95% CI [-5.51, -1.59], p < 0.01), left ventricular end-systolic diameter (LVESD) (WMD = -4.13 mm, 95% CI [-6.08, -2.18], p < 0.01), and significantly increased left ventricular ejection fraction (LVEF) (WMD = 6.30%, 95% CI [4.64, 7.96], p < 0.01) and 6-min walk test (6MWT) distance (WMD = 51.25 m, 95% CI [8.30, 94.20], p < 0.05). Brain natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were significantly reduced (standardized mean difference = -1.24, 95% CI [-1.57, -0.90], p < 0.01). In single-arm studies, RDN significantly reduced LVEDD (MC = -2.41 mm, 95% CI [-3.74, -1.09], p < 0.01), LVESD (MC = -1.72 mm, 95% CI [-2.77, -0.67], p < 0.01), left atrial diameter (MC = -1.62 mm, 95% CI [-3.16, -0.08], p < 0.01), and interventricular septal thickness (IVST) (MC = -0.76 mm, 95% CI [-1.05, -0.47], p < 0.01). RDN significantly increased LVEF (MC = 29.52%, 95% CI [12.74, 46.31], p < 0.01) and 6MWT distance (MC = 100.49 m, 95% CI [49.12, 151.86], p < 0.05). RDN significantly reduced BNP or NT-proBNP levels (SMC = -0.57, 95% CI [-0.83, -0.31], p < 0.01). Our study also found that RDN had varying degrees of reduction on renin, angiotensin II, aldosterone, and norepinephrine in HFrEF patients. Additionally, we found that RDN had no significant effect on SBP/DBP in HFrEF patients but reduced heart rate (WMD = -7.22 bpm, 95% CI [-9.84, -4.60], p < 0.01).

Our meta-analysis demonstrates that RDN can improve cardiac remodeling, enhance cardiac function, reduce CV neurohormones and has no significant effect on blood pressure in patients with HFrEF.

The field of renal denervation remains challenged by the inability to confirm successful ablation of the targeted renal sympathetic nerves. The availability of technology to measure regional blood flow in real time makes sympathetic control of the renal vasculature a logical endpoint to assess effective renal denervation, but autoregulatory mechanisms mask effects on mean renal blood flow. We hypothesized that renal sympathetic vasomotion, a novel marker of rhythmic sympathetic control, reflects successive rounds of catheter-based radiofrequency renal denervation. To test this, ten pigs underwent unilateral surgical renal denervation, recovered for at least seven days, and then underwent four successive rounds of catheter-based radiofrequency denervation of the contralateral kidney. Bilateral renal blood flow velocity and abdominal aortic pressure were measured before and after ablations to assess renal vasomotion. Prior to catheter-based denervation, the renal vasomotion profiles of the innervated and surgically denervated kidneys differed significantly (P < 0.005). Ablation of the largest renal branch artery reduced renal sympathetic vasomotion by 52%. Ablation of the remaining renal branch arteries reduced sympathetic vasomotion 95% from baseline and eliminated the statistical differences between surgically and catheter denervated kidneys. Two additional rounds of catheter denervation of the main renal artery did not consistently decrease renal sympathetic vasomotion magnitude any further. These results indicate that renal sympathetic vasomotion could provide intraprocedural feedback for interventionalists performing catheter-based renal denervation and thereby improve the efficacy, safety, and consistency of this antihypertensive intervention.

To evaluate the effect of para-aortic lymphadenectomy on blood pressure changes in endometrial cancer patients.

This retrospective study included patients with endometrial cancer treated surgically between 2017 and 2023. Patients undergoing para-aortic lymphadenectomy, up to the renal artery, in a non-nerve-sparing fashion, were compared with those undergoing pelvic lymphadenectomy or sentinel lymph node mapping. Data collected included age, body mass index, comorbidities including hypertension, diabetes mellitus, coronary artery disease, operative time, number of lymph nodes removed, tumor size, and postoperative complications. Preoperative blood pressure was recorded during outpatient visits, and postoperative measurements were collected daily during hospitalization and at follow-up visits. Statistical analyses assessed differences in systolic and diastolic blood pressure changes, operative outcomes, and complications.

A total of 264 patients were analyzed. Patients in the para-aortic group had significantly longer operative times. Tumor size was larger in the paraaortic group than in another group. Systolic blood pressure decreased significantly in the para-aortic group compared to the control group (para-aortic: -17 mmHg vs. non-para-aortic: -1.10 mmHg, p<0.05), with a similar trend for diastolic pressure (-8.00 mmHg vs. -0.80 mmHg, p<0.05). Chylous ascites (15.6% vs. 5.6%) and ileus (0% vs. 12%) were more common in the para-aortic group, along with the administration of radiotherapy and chemotherapy. Both systolic and diastolic blood pressures were significantly lower in paraaortic group, in both early and late postoperative follow-up measures (p<0.005).

Aortic lymphadenectomy is associated with decreased blood pressure and may have therapeutic potential for hypertensive patients, highlighting the need for prospective randomized studies to explore this effect further.

Activation of the sympathetic nervous system has been attributed to the development of hypertension. Two established approaches for treating hypertension are pharmacotherapy and lifestyle changes. With an improved understanding of renal nerve anatomy and physiology, renal denervation has been proposed as an alternative treatment for hypertension. Specifically, it has been shown that the interruption of sympathetic nerves connecting the kidney and the sympathetic nervous system can reduce blood pressure. Here, we present a review on how renal denervation can help hypertension patients, specifically focusing on our novel understanding of renal nerve anatomy, denervation technique, and subsequent clinical trials, and how it may be used to treat other cardiovascular diseases like heart failure.

The intricate role of the autonomic nervous system (ANS) in regulating cardiac physiology has long been recognized. Aberrant function of the ANS is central to the pathophysiology of cardiovascular diseases. It stands to reason, therefore, that neuroscience-based cardiovascular therapeutics hold great promise in the treatment of cardiovascular diseases in humans. A decade after the inaugural edition, this White Paper reviews the current state of understanding of human cardiac neuroanatomy, neurophysiology and pathophysiology in specific disease conditions, autonomic testing, risk stratification, and neuromodulatory strategies to mitigate the progression of cardiovascular diseases.

The Food and Drug Administration (FDA) recently approved renal denervation to treat resistant hypertension. This procedure is a minimally invasive procedure that starts by placing a catheter in the renal artery. This catheter is used to send either radiofrequency heat or ultrasound waves to burn the superficial nerves surrounding the renal arteries while making certain no damage happens to the renal arteries themselves. This procedure is done after a renal angiogram to ensure patency of the renal artery. Each radiofrequency ablation will take 1-2 minutes, depending on the device used. The radiofrequency balloon generator requires one single application of the radiofrequency pulse. The radiofrequency generator that uses a catheter tube will need more than one pulse. The second approved option uses ultrasound to generate an electrical signal that is converted into ultrasound vibration, that occurs at the distal end of the catheter. This vibration heats the system around the nerves, disrupting the superficial nerves that communicate with the central nervous system. This will result in lowering the blood pressure. We will review the studies that led to FDA approval, and the current guidelines for use. The FDA now approves both devices.

Renal denervation as an option for difficult to treat hypertension has been a concept for several decades, with recent U.S. FDA approval of new, minimally invasive devices. However, while renal denervation has the potential to improve hypertension management, several challenges require consideration prior to widespread adoption. The effect relative to sham control is modest, and generally similar to addition of a single blood pressure lowering medication. It is possible that with additional technique refinement greater effects may be possible. Key factors to consider beyond the direction, strengths, and limitations of the renal denervation technologies themselves, are an understanding of patient groups that derive greatest benefit and phenotypes or biomarkers that predict greater response. This review provides an update on these challenges in addition to the current state and future of renal denervation within the context of hypertension management and treatment.

Innovative therapies for hypertension are desperately needed given the rising prevalence and falling rates of control of hypertension despite an abundance of available medical therapies. Procedural interventions lower blood pressure without depending on adherence to medications, and endovascular renal denervation (RDN) is the interventional procedure with the best evidence base for the treatment of hypertension. After nearly two decades of study, with major refinements to devices, technique and trial design, two different systems for RDN received approval from the FDA in late 2023 for the treatment of hypertension. These decisions were based on a portfolio of sham-controlled clinical trials demonstrating efficacy and safety of both radiofrequency and ultrasound RDN in treating patients across the spectrum of hypertension, including patients with mild disease taking no or one medication as well as those with moderate and truly resistant hypertension. In this Review, we begin by summarizing the background and scope of the global problem of hypertension control and explore the evolution and mechanism of RDN. We then detail early studies and randomized clinical trials demonstrating the efficacy and safety of RDN procedures, review international statements, and provide practical guidance on patient selection and implementation of RDN, including the crucial aspects of building a hypertension team and of involving patients in shared decision-making.

People living with resistant hypertension (RH) are at high risk of adverse cardiovascular events. The British and Irish Hypertension Society has identified suspected RH as a condition for which specialist guidance may improve rates of blood pressure control and help clinicians identify those individuals who may benefit from specialist review. In this position statement we provide a practical approach for the investigation and management of adults with RH. We highlight gaps in the current evidence and identify important future research questions. Our aim is to support the delivery of high-quality and consistent care to people living with RH across the UK and Ireland.

Renal denervation lowers blood pressure (BP) in patients with uncontrolled hypertension. We conducted an unbiased genomic screen to identify genetic variants that may associate with BP response to renal denervation (RDN).

Patients (n=268) with uncontrolled resistant hypertension (baseline BP, 166±21/90±15 mm Hg) who underwent endovascular RDN using the Symplicity catheter (Medtronic, Inc, Santa Rosa, CA) were included. Reduction in 24-hour ambulatory systolic BP was assessed at 6 months and divided into 2 groups: above and below the median response of 6.0 mm Hg, taking preintervention 24-hour ambulatory BP and regression to the mean into account. Whole exome sequencing assessing 249 669 variants, was conducted using Illumina NovaSeq technology read on a NovaSeq S4 Flow Cell device.

We did not identify individual gene variants associated with BP response following RDN. These findings were confirmed after adjustment for sex and in a sensitivity analysis looking at tertiles of BP response. We also explored specific variants in AGT, ADD1, ADRB1, ADRB2, and SCNN1A that have been proposed as potential candidate genes for response and found no association (all P>0.13). Gene ontology analysis of variants across the 2 responder groups highlighted differences in biologic processes such as cell adhesion and molecular function such as protein tyrosine kinase activity.

The response to RDN, in terms of 24-hour BP reduction, was not associated with the genetic profile of patients with resistant hypertension. These data do not support the use of a genetic score to identify potential responders to RDN.

Renal artery denervation has re-emerged as a potential therapeutic option for patients with hypertension, especially those resistant to conventional pharmacotherapy. This comprehensive review explores the importance of careful patient selection, procedural techniques, clinical efficacy, safety considerations, and future directions of renal artery denervation in hypertension management. Drawing upon a wide range of available evidence, this review aims to provide a thorough understanding of the procedure and its role in contemporary hypertension treatment paradigms.

This study aimed to systematically evaluate the effectiveness and safety of renal denervation (RDN) in managing heart failure with reduced ejection fraction (HFrEF).

A comprehensive search was done in multiple databases: Cochrane Library, PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data, and VIP Database for Chinese Technical Periodicals. All clinical trials investigating RDN treatment for HFrEF through 15 March 2024 were gathered. The quality of the included studies was evaluated utilizing the Cochrane risk assessment tool. The pertinent data were gathered, and a meta-analysis was done using Review Manager 5.3, accompanied by sensitivity and publication bias analyses.

After applying the inclusion and exclusion criteria, eight randomized controlled trials (RCTs) were selected for analysis, encompassing 314 patients; 154 patients underwent RDN treatment during hospitalization, while 150 were randomized to the control group to receive medication therapy. The meta-analysis demonstrated that compared to medication therapy, RDN contributed to a 9.59% increase in left ventricular ejection fraction (LVEF) (95% CI: 7.92-11.27, Z = 11.20, p < 0.01); a decrease in brain natriuretic peptide (BNP) (95% CI: -364.19--191.75, Z = 6.32, p < 0.01); a decrease in N-terminal pro B-type natriuretic peptide (NT-proBNP) (95% CI: -1300.15--280.95, Z = 3.04, p < 0.01); a decrease in the New York Heart Association (NYHA) classification (95% CI: -1.58--0.34, Z = 3.05, p < 0.01); a 90.00-m increase in 6-min walk test (6MWT) (95% CI: 68.24-111.76, Z = 8.11, p < 0.01); a reduction of 4.05 mm in left ventricular end-diastolic diameter (LVEDD) (95% CI: -5.65--2.48, Z = 5.05, p < 0.01); a decrease of 4.60 heart beats·min-1 (95% CI: -8.83--0.38, Z = 2.14, p < 0.05); and a 4.67-mm reduction in left atrial diameter (LAD) (95% CI: -6.40--2.93, Z = 5.27, p < 0.01). Left ventricular end-systolic diameter (LVESD) and systolic/diastolic blood pressure (OSBP/ODBP) were similar between groups (p > 0.01). As the safety indicator, estimated glomerular filtration rate (eGFR) improved by 7.11 in the RDN group [ml/(min·1.73 m2)] (95% CI: 1.10-13.12, Z = 2.32, p < 0.05). LVEF, BNP, 6MWT, LVEDD, LAD and eGFR were meta-analyzed using a fixed-effects model, the other indicators a random-effects model.

RDN significantly ameliorated cardiac function in HFrEF patients while exhibiting commendable safety.

To evaluate the long-term efficacy and safety of transfemoral access (TFA) versus upper extremity access (UEA) for renal denervation (RDN) based on vascular morphology. This study retrospectively enrolled patients with resistant hypertension who underwent RDN treatment via TFA and UEA (brachial, radial, and ulnar artery) at the Fuwai Hospital between February 2012 and November 2019. Follow-up was conducted at 6 months, 1 year, and 3 years after RDN, and the last visit was June 2023. A total of 85 patients were enrolled, 58 (68.2%) of them were treated via TFA, and 27 patients (31.8%) via UEA. The fluoroscopy time was less in the TFA group (12.2 ± 5.7 min vs. 15.2 ± 7.2 min; p = 0.038). The procedure time (TFA group: 40.8 ± 14.9 min vs. UEA group: 38.6 ± 11.6 min; p = 0.506), contrast volume (TFA group: 78.2 ± 25.9 mL vs. UEA group: 91.9 ± 39.7 mL; p = 0.061) were similar between two groups, without procedure-related complications. Fifty-eight participants completed the last visit with a 3-12 year of follow-up (9.5 ± 1.3 years). Compared with baseline, there were no significant differences in the change of office systolic blood pressure (-12.6 ± 21.6 mmHg vs. -13.1 ± 22.8 mmHg; p = 0.933), 24-h mean systolic blood pressure (-11.9 ± 14.2 mmHg vs. -11.3 ± 15.3 mmHg; p = 0.899), the number of antihypertensive drugs, and renal function between two groups. There were three adverse events in the TFA group (3 of 58 patients, 5.2%) versus one (1 of 27 patients, 3.7%) in the UEA group, without a significant difference between the two groups. The study showed RDN via UEA was feasible using a special-designed catheter, particularly in patients with illegal vascular morphology via TFA.

Heart failure (HF) and renal dysfunction often coexist and interact in many complex and bidirectional pathways, leading to detrimental effects on patient outcomes. The treatment of HF patients with renal dysfunction presents a significant clinical challenge. Interestingly, sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), may have beneficial effects on cardiac and renal outcomes in patients with HF with reduced ejection fraction, particularly by slowing the rate of decrease in the estimated glomerular filtration rate compared to a single angiotensin-converting enzyme inhibitor. Recently, more reports have emphasized the renal protection of sacubitril/valsartan in patients with HF. In HF patients with renal dysfunction, however, there is no strong evidence supporting the use of sacubitril/valsartan to reduce the absolute risk of hyperkalemia and worsening renal function; therefore, the administration of ARNI requires a careful balance between the benefits and risks. Furthermore, the lack of evidence-based management highlights the importance of an individualized approach based on published experience and multidisciplinary collaborations, as well as underlines the need for in-depth studies investigating the underlying mechanisms in cardiorenal interactions with a focus on treatments.

This is the first consensus statement of the Joint Committee on Renal Denervation of the Japanese Society of Hypertension (JSH)/Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT)/Japanese Circulation Society (JCS). The consensus is that the indication for renal denervation (RDN) is resistant hypertension or "conditioned" uncontrolled hypertension, with high office and out-of-office blood pressure (BP) readings despite appropriate lifestyle modification and antihypertensive drug therapy. "Conditioned" uncontrolled hypertension is defined as having one of the following: 1) inability to up-titrate antihypertensive medication due to side effects, the presence of complications, or reduced quality of life. This includes patients who are intolerant of antihypertensive drugs; or 2) comorbidity at high cardiovascular risk due to increased sympathetic nerve activity, such as orthostatic hypertension, morning hypertension, nocturnal hypertension, or sleep apnea (unable to use continuous positive airway pressure), atrial fibrillation, ventricular arrythmia, or heart failure. RDN should be performed by the multidisciplinary Hypertension Renal Denervation Treatment (HRT) team, led by specialists in hypertension, cardiovascular intervention and cardiology, in specialized centers validated by JSH, CVIT, and JCS. The HRT team reviews lifestyle modifications and medication, and the patient profile, then determines the presence of an indication of RDN based on shared decision making with each patient. Once approval for real-world clinical use in Japan, however, the joint RDN committee will update the indication and treatment implementation guidance as appropriate (annually if necessary) based on future real-world evidence.

Renal nerves play a critical role in cardiorenal interactions. Renal denervation (RDN) improved survival in some experimental heart failure (HF) models. It is not known whether these favorable effects are indirect, explainable by a decrease in vascular afterload, or diminished neurohumoral response in the kidneys, or whether RDN procedure per se has direct myocardial effects in the failing heart. To elucidate mechanisms how RDN affects failing heart, we studied load-independent indexes of ventricular function, gene markers of myocardial remodeling, and cardiac sympathetic signaling in HF, induced by chronic volume overload (aorto-caval fistula, ACF) of Ren2 transgenic rats. Volume overload by ACF led to left ventricular (LV) hypertrophy and dysfunction, myocardial remodeling (upregulated Nppa, MYH 7/6 genes), increased renal and circulating norepinephrine (NE), reduced myocardial NE content, increased monoaminoxidase A (MAO-A), ROS production and decreased tyrosine hydroxylase (+) nerve staining. RDN in HF animals decreased congestion in the lungs and the liver, improved load-independent cardiac function (Ees, PRSW, Ees/Ea ratio), without affecting arterial elastance or LV pressure, reduced adverse myocardial remodeling (Myh 7/6, collagen I/III ratio), decreased myocardial MAO-A and inhibited renal neprilysin activity. RDN increased myocardial expression of acetylcholinesterase (Ache) and muscarinic receptors (Chrm2), decreased circulating and renal NE, but increased myocardial NE content, restoring so autonomic control of the heart. These changes likely explain improvements in survival after RDN in this model. The results suggest that RDN has remote, load-independent and favorable intrinsic myocardial effects in the failing heart. RDN therefore could be a useful therapeutic strategy in HF.

This is the first consensus statement of the Joint Committee on Renal Denervation of the Japanese Society of Hypertension (JSH)/Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT)/Japanese Circulation Society (JCS). The consensus is that the indication for renal denervation (RDN) is resistant hypertension or "conditioned" uncontrolled hypertension, with high office and out-of-office blood pressure (BP) readings despite appropriate lifestyle modification and antihypertensive drug therapy. "Conditioned" uncontrolled hypertension is defined as having one of the following: (1) inability to up-titrate antihypertensive medication due to side effects, the presence of complications, or reduced quality of life. This includes patients who are intolerant of antihypertensive drugs; or (2) comorbidity at high cardiovascular risk due to increased sympathetic nerve activity, such as orthostatic hypertension, morning hypertension, nocturnal hypertension, or sleep apnea (unable to use continuous positive airway pressure), atrial fibrillation, ventricular arrythmia, or heart failure. RDN should be performed by the multidisciplinary Hypertension Renal Denervation Treatment (HRT) team, led by specialists in hypertension, cardiovascular intervention and cardiology, in specialized centers validated by JSH, CVIT, and JCS. The HRT team reviews lifestyle modifications and medication, and the patient profile, then determines the presence of an indication of RDN based on shared decision making with each patient. Once approval for real-world clinical use in Japan, however, the joint RDN committee will update the indication and treatment implementation guidance as appropriate (annually if necessary) based on future real-world evidence.

This review explores the various pathophysiological factors influencing antihypertensive effects, involving the regulation of vascular resistance, plasma volume, cardiac function, and the autonomic nervous system, emphasizing the interconnected processes regulating blood pressure (BP). The kidney's pivotal role in BP control and its potential contribution to hypertension is complicated but important to understand the effective mechanisms of renal denervation (RDN), which may be a promising treatment for resistant hypertension. Excessive stimulation of the sympathetic nervous system or the renin-angiotensin-aldosterone system (RAAS) can elevate BP through various physiological changes, contributing to chronic hypertension. Renal sympathetic efferent nerve activation leads to elevated norepinephrine levels and subsequent cascading effects on vasoconstriction, renin release, and sodium reabsorption. RDN reduces BP in resistant hypertension by potentially disrupting sensory afferent nerves, decreasing feedback activation to the central nervous system, and reducing efferent sympathetic nerve activity in the heart and other structures. RDN may also modulate central sympathetic outflow and inhibit renal renin-angiotensin system overactivation. While evidence for RDN efficacy in hypertension is increasing, accurate patient selection becomes crucial, considering complex interactions that vary among patients. This review also discusses methods to evaluate autonomic nerve activity from the golden standard to new potential examination for finding out optimization in stimulation parameters or rigorous patient selection based on appropriate biomarkers.

The efficacy of renal denervation (RDN) has been controversial, but recent randomized sham-controlled trials demonstrated significant blood pressure reductions after RDN in patients with hypertension. We conducted a systematic review and updated meta-analysis to evaluate the effects of RDN on ambulatory and office blood pressures in patients with hypertension. Databases were searched up to 15 November 2023 to identify randomized, sham-controlled trials of RDN. The primary endpoint was change in 24 h ambulatory systolic blood pressure (SBP) with RDN versus sham control. The secondary endpoints were changes in 24 h ambulatory diastolic blood pressure, daytime and nighttime blood pressure (BP), office BP, and home BP. A sub-analysis determined outcomes by medication, procedure, and device. From twelve trials, 2222 patients with hypertension were randomized to undergo RDN (n = 1295) or a sham procedure (n = 927). At 2-6 months after treatment, RDN significantly reduced 24 h ambulatory SBP by 2.81 mmHg (95% confidence interval: -4.09, -1.53; p < 0.001) compared with the sham procedure. RDN also reduced daytime SBP by 3.17 mmHg (- 4.75, - 1.58; p < 0.001), nighttime SBP by 3.41 mmHg (- 4.69, - 2.13; p < 0.001), office SBP by 4.95 mmHg (- 6.37, - 3.54; p < 0.001), and home SBP by 4.64 mmHg (- 7.44, - 1.84; p = 0.001) versus the sham control group. There were no significant differences in the magnitude of BP reduction between first- and second-generation trials, between devices, or between with or without medication. These data from randomized sham-controlled trials showed that RDN significantly reduced all blood pressure metrics in medicated or unmedicated patients with hypertension, including resistant/uncontrolled hypertension.

Renal denervation (RDN) is a minimally invasive, endovascular catheter-based procedure using radiofrequency, ultrasound, or alcohol-mediated ablation to treat resistant hypertension. RDN gained popularity in 2009 when it was shown to have an antihypertensive effect. However, concerns about the efficacy of RDN were raised in the HTN-3 trial published in 2014, and the development of several RDN devices was then discontinued. In the process, new randomized controlled trials were conducted after the development of some of the RDN devices, the quality assurance of the procedure, changes in ablation points, and improvements in study design. In November 2023, the U.S. Food and Drug Administration approved a radiofrequency RDN device and an ultrasound RDN device. The results of a randomized controlled trial of an alcohol-mediated RDN device have been published, and future trends are being watched closely. In this mini-review, we summarize the differences in the antihypertensive effect and safety of the different RDN devices and the endpoints of the procedure in order to contribute to the further development of RDN devices Currently available renal denervation device. A multielectrode radiofrequency ablation (Spyral), (B) ultrasound denervation (Paraise), and (C) alcohol-mediated perivascular denervation (Peregrine). ASBP ambulatory systolic blood pressure, ADBP ambulatory diastolic blood pressure, OSBP office systolic blood pressure, ODBP office diastolic blood pressure. Analysis according to types of renal denervation device (radiofrequency, ultrasound, or alcohol-mediated device). P values for interaction were 0.578 (ambulatory SBP), 0.499 (ambulatory diastolic BP), 0.853 (office SBP), and 0.870 (office diastolic BP).

The study aims to compare the outcomes of different renal denervation (RDN) procedures in the treatment of uncontrolled hypertension. We searched Scopus, PubMed, Web of Science, and Cochrane for RCTs evaluating different procedures of RDN for hypertension. The outcomes of this study were systolic blood pressure (SBP) daytime, diastolic blood pressure (DBP) daytime, SBP nighttime, DBP nighttime, SBP 24-hour, DBP 24-hour, SBP home, DBP home, SBP office, and DBP office. We did a frequentist network meta-analysis of 38 published RCTs evaluating the efficacy of different renal artery denervation procedures for uncontrolled hypertension compared to sham procedures or standardized stepped-care antihypertensive treatment (SSAHT). Radiofrequency (RF) alone showed a statistically significant reduction in DBP (24 hours), DBP (daytime), and DBP (nighttime): standardized mean difference (SMD): -2.01 (95% CI: (-3.34; -0.68)), SMD: -4.36 (95% CI: (-8.28; -0.44)), and SMD: -3.50 (95% CI: (-6.23; -0.76)), respectively, and showed a statistically significant reduction in SBP (24 hours), SBP (daytime), and SBP (nighttime): SMD: -3.93 (95% CI: (-6.01; -1.84)), SMD: -5.88 (95% CI: (-9.91; -1.85)), and SMD: -5.79 (95% CI: (-10.0; -1.58)), respectively. RF added to SSAHT has statistical significance in the reduction of DBP (nighttime), SBP (daytime), SBP (home), and SBP (nighttime) with a SMD of -7.63 (95% CI: (-14.21; -1.06)), SMD of -10.56 (95% CI: (-21.03; -0.08)), SMD of -23.20 (95% CI: (-36.72; -9.26)), and SMD of -14.03 (95% CI: (-25.43; -2.63)), respectively. We found that renal denervation, especially by RF, when added to SSAHT may be a promising therapeutic option for patients with treatment-resistant hypertension, particularly in cases where medication alone fails to achieve adequate blood pressure control.

Hypertension is a significant risk factor for cardiovascular and chronic kidney diseases. Its management in young people remains limited. Device-based therapies, such as low-level tragus stimulation (LL-TS), a noninvasive method that reduces sympathetic activity, have recently been explored for resistant hypertension.

This trial involved patients with Grade 1 hypertension with no other medical history. LL-TS (20 Hz, 1 mA, 1 h/day) was applied for 3 months on the tragus (Intervention group [IG]) or earlobe (Control group [CG]). Blood pressure and outcomes were assessed at the first, second, and third months. Among 40 patients, 21 were in IG and 19 in CG. Baseline systolic blood pressure was similar between IG (142.62±8.18 mm Hg) and CG (143.00±8.61 mm Hg), P=0.89. Post-LL-TS, systolic blood pressure showed significant reductions in IG compared with CG at the first (IG: 134.47±5.95 mm Hg, CG: 141.28±6.78 mm Hg, P=0.002), second (IG: 132.50±7.51 mm Hg, CG: 140.62±7.15 mm Hg, P=0.001), and third months (IG: 128.81±7.13 mm Hg, CG: 136.51±7.96 mm Hg, P=0.003). diastolic blood pressure also differed significantly: first month (IG: 85.34±5.81 mm Hg, CG: 89.74±6.32 mm Hg, P=0.03), second month (IG: 82.12±5.22 mm Hg, CG: 88.57±7.11 mm Hg, P=0.002), and third month (IG: 80.71±5.96 mm Hg, CG: 87.55±5.26 mm Hg, P=0.001). Heart rate was unchanged (P>0.05). Only 0.01% of IG subjects reported site irritation, with no serious adverse events.

LL-TS led to significant blood pressure reductions in young patients with essential hypertension. Further larger trials are needed to confirm the safety and efficacy of LL-TS.

URL: https://www.chictr.org.cn/; Unique identifier: ChiCTR2000038448.

This is the first consensus statement of the Joint Committee on Renal Denervation of the Japanese Society of Hypertension (JSH)/Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT)/Japanese Circulation Society (JCS). The consensus is that the indication for renal denervation (RDN) is resistant hypertension or "conditioned" uncontrolled hypertension, with high office and out-of-office blood pressure (BP) readings despite appropriate lifestyle modification and antihypertensive drug therapy. "Conditioned" uncontrolled hypertension is defined as having one of the following: 1) inability to up-titrate antihypertensive medication due to side effects, the presence of complications, or reduced quality of life. This includes patients who are intolerant of antihypertensive drugs; or 2) comorbidity at high cardiovascular risk due to increased sympathetic nerve activity, such as orthostatic hypertension, morning hypertension, nocturnal hypertension, or sleep apnea (unable to use continuous positive airway pressure), atrial fibrillation, ventricular arrythmia, or heart failure. RDN should be performed by the multidisciplinary Hypertension Renal Denervation Treatment (HRT) team, led by specialists in hypertension, cardiovascular intervention and cardiology, in specialized centers validated by JSH, CVIT, and JCS. The HRT team reviews lifestyle modifications and medication, and the patient profile, then determines the presence of an indication of RDN based on shared decision making with each patient. Once approval for real-world clinical use in Japan, however, the joint RDN committee will update the indication and treatment implementation guidance as appropriate (annually if necessary) based on future real-world evidence.

Renal Denervation (RDN) is a novel non-pharmacological technique to treat hypertension. This technique lowers blood pressure by blocking the sympathetic nerve fibers around the renal artery, then causing a decrease in system sympathetic nerve excitability. This study aimed to visualize and analyze research hotspots and development trends in the field of RDN for hypertension through bibliometric analysis.

In total, 1479 studies were retrieved on the Web of Science Core Collection (WoSCC) database from 2004 to 2023. Using CiteSpace (6.2.R4) and VOSviewer (1.6.18), visualization maps were generated by relevant literature in the field of RDN for hypertension to demonstrate the research status and frontiers.

The number of publications was found to be generally increasing. Europe and the United States were the first countries to carry out research on different techniques and related RDN clinical trials. The efficacy and safety of RDN have been repeatedly verified and gained increasing attention. The study involves multiple disciplines, including the cardiovascular system, peripheral vascular disease, and physiological pathology, among others. Research hotspots focus on elucidating the mechanism of RDN in the treatment of hypertension and the advantages of RDN in appliance therapy. Additionally, the research frontiers include improvement of RDN instruments and techniques, as well as exploration of the therapeutic effects of RDN in diseases with increased sympathetic nerve activity.

The research hotspots and frontiers reflect the status and development trend of RDN in hypertension. In the future, it is necessary to strengthen international collaboration and cooperation, conduct long-term clinical studies with a large sample size, and continuously improve RDN technology and devices. These measures will provide new options for more patients with hypertension, thereby improving their quality of life.

Renal sympathetic denervation (RDN) is an interventional supplement to medical treatment in patients with arterial hypertension. While the first sham-controlled trial, SYMPLICITY HTN‑3 was neutral, with improved procedural details, patient selection and follow-up, recent randomized sham-controlled trials of second-generation devices show a consistent blood pressure lowering effect of RDN, as compared to sham controls. These new data and the recent U.S. Food and Drug Administration (FDA) premarket approval of two RDN devices are the basis for the present recommendations update.This joint position paper from the Austrian Society of Hypertension, together with the Austrian Society of Nephrology and the Working Group of Interventional Cardiology from the Austrian Society of Cardiology includes an overview about the available evidence on RDN and gives specific recommendations for the work-up, patient selection, pretreatment, procedural management and follow-up in patients undergoing RDN in Austria. Specifically, RDN may be used in clinical routine care, together with lifestyle measures and antihypertensive drugs, in patients with resistant hypertension (i.e. uncontrolled blood pressure on 3 antihypertensive drugs) and in those with uncontrolled hypertension, after adequate work-up, if institutional, patient-related and procedural conditions are fulfilled.

Despite optimal medical therapy, a significant proportion of patients' blood pressure remains uncontrolled. Catheter-based renal denervation (RDN) has been proposed as a potential intervention for uncontrolled hypertension. We conducted an updated meta-analysis to assess the efficacy and safety of RDN in patients with uncontrolled hypertension, with emphasis on the differential effect of RDN in patients on and off antihypertensive medications.

Online databases were searched to identify randomized clinical trials comparing efficacy and safety of RDN versus control in patients with uncontrolled hypertension. Subgroup analyses were conducted for sham-controlled trials and studies that used RDN devices that have gained or are currently seeking US Food and Drug Administration approval. Fifteen trials with 2581 patients (RDN, 1723; sham, 858) were included. In patients off antihypertensive medications undergoing RDN, a significant reduction in 24-hour ambulatory (-3.70 [95% CI, -5.41 to -2.00] mm Hg), office (-4.76 [95% CI, -7.57 to -1.94] mm Hg), and home (-3.28 [95% CI, -5.96 to -0.61] mm Hg) systolic blood pressures was noted. In patients on antihypertensive medications, a significant reduction was observed in 24-hour ambulatory (-2.23 [95% CI, -3.56 to -0.90] mm Hg), office (-6.39 [95% CI, -11.49 to -1.30]), home (-6.08 [95% CI, -11.54 to -0.61] mm Hg), daytime (-2.62 [95% CI, -4.14 to -1.11]), and nighttime (-2.70 [95% CI, -5.13 to -0.27]) systolic blood pressures, as well as 24-hour ambulatory (-1.16 [95% CI, -1.96 to -0.35]), office (-3.17 [95% CI, -5.54 to -0.80]), and daytime (-1.47 [95% CI, -2.50 to -0.27]) diastolic blood pressures.

RDN significantly lowers blood pressure in patients with uncontrolled hypertension, in patients off and on antihypertensive medications, with a favorable safety profile. The efficacy of RDN was consistent in sham-controlled trials and contemporary trials using US Food and Drug Administration-approved devices.

Obesity is widely recognized for its role in predisposing individuals to a spectrum of chronic health conditions. Emerging preliminary evidence points to the potential benefits of low-frequency transcutaneous electrical nerve stimulation (Lo-TENS) in enhancing various health outcomes among those with obesity and associated disorders.

This systematic review was designed to assess the effectiveness of Lo-TENS for managing obesity and its related chronic diseases.

For this systematic review, we included randomized controlled trials that evaluated the impact of Lo-TENS on individuals with obesity and its associated chronic diseases.

Eight trials encompassing 671 participants and spanning three unique populations: essential hypertension (EH), type 2 diabetes mellitus (T2DM), and obesity were deemed eligible for inclusion in this review. Compared to baseline measurements, Lo-TENS demonstrated a tendency to positively affect blood pressure in individuals with EH and metabolic parameters in those with T2DM. Nonetheless, the efficacy of Lo-TENS in treating obesity is not yet clear when contrasted with a no-intervention control group. When compared with other intervention modalities, three of the trials reported less favorable results.

Although Lo-TENS did not consistently surpass other treatments or yield substantial improvements, it generally provided greater benefits than the majority of placebo controls. This suggests that Lo-TENS could potentially serve as a beneficial adjunctive therapy in the management of obesity and its associated conditions. However, given the limited number of trials assessed, the elevated risk of bias within these studies, and the scarce evidence currently available, it is too early to reach definitive conclusions. Caution should be exercised when interpreting the current findings. There is an imperative for further high-quality research to thoroughly investigate and substantiate the efficacy of Lo-TENS in relation to obesity and its related disorders.

Cardiovascular disease is the most common cause of death worldwide, resulting in millions of deaths annually. Currently, there are still some deficiencies in the treatment of cardiovascular diseases. Innovative surgical treatments are currently being developed and tested in response to this situation. Large animal models, which are similar to humans in terms of anatomy, physiology, and genetics, play a crucial role in connecting basic research and clinical applications. This article reviews recent preclinical studies and the latest clinical advancements in cardiovascular disease based on large animal models, with a focus on targeted delivery, neural regulation, cardiac remodeling, and hemodynamic regulation. It provides new perspectives and ideas for clinical translation and offers new methods for clinical treatment.

The objective of this study was to characterize hemodynamic changes during trans-vascular stimulation of the renal nerve and their dependence on stimulation parameters. We employed a stimulation catheter inserted in the right renal artery under fluoroscopic guidance, in pigs. Systolic, diastolic and pulse blood pressure and heart rate were recorded during stimulations delivered at different intravascular sites along the renal artery or while varying stimulation parameters (amplitude, frequency, and pulse width). Blood pressure changes during stimulation displayed a pattern more complex than previously described in literature, with a series of negative and positive peaks over the first two minutes, followed by a steady state elevation during the remainder of the stimulation. Pulse pressure and heart rate only showed transient responses, then they returned to baseline values despite constant stimulation. The amplitude of the evoked hemodynamic response was roughly linearly correlated with stimulation amplitude, frequency, and pulse width.

Resistant hypertension is defined as blood pressure that remains above the therapeutic goal despite concurrent use of at least three antihypertensive agents of different classes, including a diuretic, with all agents administered at maximum or maximally tolerated doses. Resistant hypertension is also diagnosed if blood pressure control requires four or more antihypertensive drugs. Assessment requires the exclusion of apparent treatment resistant hypertension, which is most often the result of non-adherence to treatment. Resistant hypertension is associated with major cardiovascular events in the short and long term, including heart failure, ischemic heart disease, stroke, and renal failure. Guidelines from several professional organizations recommend lifestyle modification and antihypertensive drugs. Medications typically include an angiotensin converting enzyme inhibitor or angiotensin receptor blocker, a calcium channel blocker, and a long acting thiazide-type/like diuretic; if a fourth drug is needed, evidence supports addition of a mineralocorticoid receptor antagonist. After a long pause since 2007 when the last antihypertensive class was approved, several novel agents are now under active development. Some of these may provide potent blood pressure lowering in broad groups of patients, such as aldosterone synthase inhibitors and dual endothelin receptor antagonists, whereas others may provide benefit by allowing treatment of resistant hypertension in special populations, such as non-steroidal mineralocorticoid receptor antagonists in patients with chronic kidney disease. Several device based approaches have been tested, with renal denervation being the best supported and only approved interventional device treatment for resistant hypertension.

Resistant hypertension is diagnosed in patients whose blood pressure target is unmet despite the use of three or more antihypertensive medications. Systemic sympathetic hyperactivation is associated with the development of resistant hypertension. As the kidney is largely pervasive of the sympathetic nervous system renal denervation procedure was developed to control blood pressure by attenuating the renal and systemic sympathetic hyperactivity. Renal denervation is a minimally invasive procedure that uses radiofrequency or ultrasound energy waves to reduce the activity of the renal artery nerves. Previous clinical trials have shown conflicting results regarding the efficacy of the procedure. Symplicity HTN-1 and -2 trials showed effective blood pressure lowering results in the renal denervation group with a good safety profile. However, the Symplicity HTN-3 trial showed no difference in blood pressure lowering effect between the renal denervation and control Sham procedure groups. Notwithstanding, some recent clinical trials with Sham control and meta-analysis showed clinical benefits of renal denervation. Other clinical benefits of renal denervation include glucose control, cardiovascular protective effect, reduction of obstructive sleep apnea, and neuralgia control. A subset of patients with satisfactory blood pressure control response to the procedure may experience improved glucose control due to the overall reduced sympathetic activity and insulin resistance. Sympathetic activity control after renal denervation has cardioprotective effects, especially for those with arrhythmia and left ventricular hypertrophy. Also, renal denervation could be helpful in renalorigin pain control. Renal denervation is an effective, safe, non-invasive procedure with many clinical benefits beyond blood pressure control. Further development in the procedure technique and selection of target patients are needed for wider clinical use of renal denervation in resistant hypertension.

The importance of the sympathetic nervous system in essential hypertension has been recognized in 2 eras. The first was in early decades of the 20th century, through to the 1960s. Here, the sympathetic nervous system was identified as a target for the treatment of hypertension, and an extensive range of antiadrenergic therapies were developed. Then, after a period of lapsed interest, in a second era from 1985 on, the development of precise measures of human sympathetic nerve firing and transmitter release allowed demonstration of the importance of neural mechanisms in the initiation and maintenance of the arterial blood pressure elevation in hypertension. This led to the development of a device treatment of hypertension, catheter-based renal denervation, which we will discuss.

Hypertension is associated with cardiovascular dysfunction, dysregulation of the antioxidant system and alteration of the level of some enzymes in the metabolic pathway. The possible modulatory effect of acute renal denervation (ARD) on cardiovascular function and the antioxidant system is still a subject of intense debate. This study sought to ascertain the ameliorative effects of ARD on cardiovascular parameters, antioxidant system, creatine kinase and lactate dehydrogenase levels.

Thirty-six Sprague-Dawley rats (5-6 weeks old) were divided into 6 groups of 6 animals each consisting of Normal Salt, High Salt, Normal Salt + Sham Denervation, High Salt + Sham Denervation, Normal Salt + Renal Denervation and High Salt + Renal Denervation. Induction of hypertension with 8 % salt in the diet lasted for 8 weeks. Renal or Sham denervation was thereafter done on selected groups. At the end of the experimental period, cardiovascular parameters, plasma antioxidant status, plasma creatine kinase (CK) and lactate dehydrogenase (LDH) levels were assessed. Significance level was set at p < 0.05.

Salt-loading significantly increased systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MABP), rate pressure product (RPP) while reducing superoxide dismutase (SOD), reduced glutathione (GSH) and catalase (CAT). Acute renal denervation significantly (p < 0.0001) reduced SBP, DBP, MABP, RPP, LDH and norepinephrine level while increasing SOD, GSH and CAT. ARD did not significantly alter CK level.

Acute renal denervation, by reducing sympathetic activity, ameliorates cardiovascular and antioxidant functions as well as reduces LDH level without significantly altering CK level in salt-induced hypertension.