Renal denervation as an option for the management of hypertension

Hypertension is a multifactorial condition which makes the development of treatment approaches difficult. The vast majority of patients are treated with lifestyle measures either alone or in combination with antihypertensive drugs, and this approach is largely successful in controlling blood pressure. However, for a subgroup of patients, control of blood pressure remains resistant to this approach and therefore the development of new strategies is im- perative. The sympathetic nervous system has been known to be implicated in hypertension for many decades, and evidence from studies in the past has revealed the benefit of reducing sympathetic nerve activity in the control of blood pressure albeit with severe side effects. Recent technological advances have allowed for specific targeting of the renal sympathetic nerves by catheter ablation. The Symplicity HTN-1 and HTN-2 trials have provided strong evidence for renal denervation giving rise to considerable blood pressure reductions in treatment-resistant hyper- tensives and, due to the high incidence of hypertension worldwide, this carries the promise of further reducing the global burden of hypertension and its attendant complications. Here we review the evidence for renal denervation in the management of hypertension.

Comparison of a 5 F Microtube-Irrigated Ablation Catheter and a General Ablation Catheter in the Treatment of Resistant Hypertension with Renal Denervation

Objective:To assess the effectiveness of catheter-based renal denervation for reducing blood pressure in patients with resistant hypertension using a 5 F microtube-irrigated ablation catheter.Methods:Sixty patients with resistant hypertension were divided into two groups:a microtube-irrigated ablation catheter group and a general ablation catheter group.We conducted 12-month follow-up of all patients and recorded clinical blood pressure,ambulatory blood pressure,medication use,and biochemistry test results in both groups at the baseline and at the 12-month follow-up.Results:All patients underwent renal denervation.At the 6-month follow-up,ambulatory blood pressure in the mi-crotube-irrigated ablation catheter group was signifi cantly lower than in the general ablation catheter group(systolic blood pressure 142.0±14.4 mmHg vs.150.8±17.9 mmHg,P=0.04;diastolic blood pressure 81.2±7.0 mmHg vs.87.6±8.0 mmHg,P=0.002).At the 12-month follow-up,the between-group difference in ambulatory blood pressure was not statistically signifi cant.At the 12-month follow-up,the number of antihypertensive drugs and diuretics used in the microtube-irrigated ablation catheter group was less than in the general ablation catheter group(P=0.043).There was no statistical difference between the two groups in the results of biochemistry tests and echocardiography.Conclusion:The microtube-irrigated ablation catheter is more effective in treating hypertension than the general ablation catheter at the 6-month follow up and thus fewer antihypertensive drugs were used in the microtube-irrigated ablation catheter group than in the general ablation catheter group.

Main Renal Artery Plus Branch Ablation in the Treatment of Resistant Hypertension with Renal Denervation

Objective:To study the safety and effi cacy of denervation of renal artery branches in the treatment of resistant hy-pertension.Methods:Sixty patients with resistant hypertension were enrolled.The patients were randomly assigned to the main renal artery plus branch ablation group or the main renal artery ablation group.The clinical data and operation-related parameters,including number of ablation points,temperature,and average energy,were recorded.Ambulatory blood pressure was taken for all patients at the baseline and at 6 months after treatment.Offi ce blood pressure was recorded before treatment and after treatment every 3 months for 2 years.Results:Sixty patients with resistant hypertension were enrolled in this study.There were 30 patients in each group.Angiography was performed after ablation.No renal artery complications,such as stenosis and dissection,occurred in the two groups.There was no signifi cant difference in age,sex,BMI,comorbid disease,and medication between the two groups(P>0.05).The number of ablation points for the main renal artery plus branch ablation group was greater than that for the main renal artery ablation group.The offi ce blood pressure and 24-hour blood pressure were signifi cantly lower 6 months after treatment than before treatment in both groups(P<0.05).Offi ce blood pressure in the main renal artery plus branch ablation group was lower than that in the main renal artery ablation group during the 3-12-month follow-up period,with a statistical difference.However,as the follow-up time increased,the difference disappeared.Conclusion:The results of this study show that main renal artery plus branch ablation is a safe interventional method,but there was no obvious advantage on long-term follow-up compared with only main renal artery ablation.

Effects of renal sympathetic denervation on cardiac systolic function after myocardial infarction in rats

This study investigated the therapeutic effects of renal denervation on cardiac systolic function after myocardial infarction （MI） in rats and the mechanism involved. Fifty male SD rats were randomly assigned to the sham group （n = 15）, the MI group （n = 20）, and the MI plus renal denervation group （n = 15）. MI was established through thoracotomic ligation of the anterior descending artery. Renal denervation was achieved by laparotomic stripping of the renal arterial adventitial sympathetic nerve, approximately 3 mm from the abdominal aorta. Left ventricular function and hemodynamics were measured several weeks following MI. The left ventricular systolic function of the MI group was significantly reduced and the systolic blood pressure （SBP） remarkably declined. In rats with MI treated with renal denervation, the left ventricular ejection fraction （EF）, fractional shortening （FS） and SBP markedly improved compared with the MI group. However, heart rate and fibrosis decreased significantly. These findings suggest that renal denervation has therapeutic effects on post-MI cardiac dysfunction. These effects are associated with increased left ventricular ejection fraction （LVEF） and SBP, as well as reduced heart rate and fibrosis. This may represent a new approach to the treatment of post-MI remodeling and subsequent heart failure.

Account for Clinical Heterogeneity in Assessment of Catheter-based Renal Denervation among Resistant Hypertension Patients： Subgroup Meta-analysis

Background： Catheter-based renal denervation （RDN） is a novel treatment tbr resistant hypertension （RH）. A recent meta-analysis reported that RDN did not significantly reduce blood pressure （BP） based on the pooled effects with mild to severe heterogeneity. The aim of the present study was to identify and reduce clinical sources of heterogeneity and reassess the safety and efficacy of RDN within the identified homogeneous subpopulations. Methods： This was a meta-analysis of 9 randomized clinical trials （RCTs） among patients with RH up to June 2016. Sensitivity analyses and subgroup analyses were extensively conducted by baseline systolic blood pressure （SBP） level, antihypertensive medication change rates, and coronary heart disease （CHD）. Results： In all patients with RH, no statistical differences were found in mortality, severe cardiovascular events rate, and changes in 24-11 SBP and office SBP at 6 and 12 months. However, subgroup analyses showed significant differences between the RDN and control groups. In the subpopulations with baseline 24-h SBP 〉 155 mmHg （ 1 mmHg = 0.133 kPa） and the infrequently changed medication, the use of RDN resulted in a significant reduction in 24-h SBP level at 6 months （P = 0.100 and P = 0.009, respectively）. Subgrouping RCTs with a higher prevalent CHD in control showed that the control treatment was significantly better than RDN in office SBP reduction at 6 months （P 〈 0.001 ）. Conclusions： In all patients with RH, the catheter-based RDN is not more effective in lowering ambulatory or office BP than an optimized antihypertensive drug treatment at 6 and 12 months. However, among RH patients with higher baseline SBP, RDN might be more effective in reducing SBR

Renal denervation： a new therapeutic approach for resistant hypertension

Objective To review the advances in studies on renal denervation. Data sources References concerning renal denervation and resistant hypertension cited in this review were collected from PubMed published in English and those of renal denervation devices from official websites of device manufacturers up to January 2014. Study selection Articles with keywords ＂renal denervation＂ and ＂resistant hypertension＂ were selected. Results Renal and systemic sympathetic overactivity plays an important role in pathology of hypertension as well as other diseases characterized by sympathetic overactivity. Renal denervation is a new, catheter based procedure to reduce renal and systemic sympathetic overactivity by disruption of renal sympathetic efferent and afferent nerves through radiofrequency or ultrasound energy delivered to the endoluminal surface of both renal arteries. Although several studies have shown the efficacy and safety of renal denervation in the treatment of resistant hypertension and the potential benefit of the procedure in other diseases, Symplicity HTN 3 study, the most rigorous clinical trial of renal denervation to date, failed to meet its primary endpoint. The procedure also has other limitations such as the lack of long term, efficacy and safety data and the lack of the predictors for the blood pressure lowering response and nonresponse to the procedure. An overview of current renal denervation devices holding Conformite Europ6enne mark is also included in this review. Conclusions Renal denervation is a promising therapeutic approach in the management of resistant hypertension and other diseases characterized by sympathetic overactivity. In its early stage of clinical application, the efficacy of the procedure is still controversial. Large scale, blind, randomized, controlled clinical trials are still necessary to address the limitations of the procedure.

Effects of renal denervation on blood-pressure response to hemorrhagic shock in spontaneously hypertensive rats

Purpose： Renal denervation （RD） has been demonstrated to be an effective approach to reduce blood pressure for those with resistant hypertension. Yet, we aimed to explore the effect and possible mech- anism of RD on blood-pressure response to hemorrhagic shock in spontaneously hypertensive rats. Methods： A total of 48 male spontaneously hypertensive rats were randomized to three groups： study group, sham-operation group and control group. RD was achieved by cutting off renal nerves and swabbing phenol on it. Ten weeks after RD, 8 rats in each group were sacrificed to collect the kidney and heart tissues. The remaining rats were subjected to an operation to induce hemorrhagic shock which would lead to 40% loss of total blood volume, and observed for 120 min. The serum concentration of norepinephrine was measured before and three weeks after RD. Results： The blood-pressure and norepinephrine levels were reduced significantly after RD （p 〈 0.05）, Systolic blood pressure and diastolic blood pressure of the surgerygroup were higher than those in the sham and control groups at 15, 30 and 45 min after hemorrhagic shock （p 〈 0.05）, while no significant difference was observed at 60, 90 and 120 min （p 〉 0.05）. Additionally, the beta-1 adrenergic receptor （β1 -AR） in the study group was significantly higher than those in the other two groups （p 〈 0.05） after hemorrhagic shock. Conclusion： This study demonstrated that RD could to some extent improve blood-pressure response to hemorrhagic shock in an established model of severe hemorrhagic shock in spontaneously hypertensive rats. The mechanism might be associated with uo-regulation of β1-AR.

Consensus and inconsistency between different consensus documents on renal denervation worldwide:the way forward

Given the unsatisfactory hypertension control rates and high rates of non-adherence to antihypertensive medications worldwide,device therapy which can safely provide durable blood pressure-lowering effects can fulfill the unmet need.A series of second-generation randomized sham-controlled renal denervation(RDN)trials have demonstrated the efficacy and safety of RDN in a wide range of hypertensive patients.The four representative consensus documents on RDN(from the Chinese Taiwan Hypertension Society and Taiwan Society of Cardiology[THS/TSOC 2019],Asia Renal Denervation Consortium 2019,European Society of Hypertension[ESH 2021],and Society for Cardiovascular Angiography&Intervention and National Kidney Foundation[SCAI/NKF 2021])consistently recommend RDN as an alternative or complementary treatment strategy for patients with uncontrolled hypertension.In addition,both documents from Asia further recommend that RDN can be considered as an initial treatment strategy for drug-naïve hypertensive patients.There is still inconsistency regarding whether ambulatory blood pressure monitoring should be used routinely both before and after RDN,and whether patients with a secondary cause of hypertension could be treated with RDN if their blood pressure remains uncontrolled after definitive treatment(treatment-resistant secondary hypertension).The THS/TSOC consensus provides acronyms to summarize key aspects of patient selection(RDNi2)and pre-RDN assessments(RAS).The ESH and SCAI/NKF documents recommend establishing structured pathways for clinical practice and issues regarding reimbursement.All documents identify knowledge gaps in RDN,from identifying predictors of super-responders to demonstrating effects on cardiovascular events.These gaps should be urgently filled to facilitate the wider application of this device therapy for patients with hypertension.

Catheter-based renal sympathetic nerve denervation on hypertension management outcomes

BACKGROUND Renal sympathetic denervation(RSD)provides a minimally invasive interventional treatment modality for patients with resistant hypertension.However,the post-operative outcomes remain a key area of investigation since its earliest clinical trials.AIM To evaluate patient outcomes after RSD intervention among peer-reviewed patient cases.METHODS A systematic review of literature on MEDLINE,Google Scholar,and the Cochrane Database of Systematic Reviews for RSD case studies to assess post-operative hypertension readings and medical management.RESULTS Among 51 RSD cases,the post-operative RSD patients report an apparent reduction with a mean number of 3.1 antihypertensive medications.The mean systolic arterial blood pressure 1 year following RSD was 136.0 mmHg(95%CI:118.7-153.3).CONCLUSION The apparent improvements in office systolic blood pressure after 12 month postoperative RSD can support the therapeutic potential of this intervention for blood pressure reduction.Additional studies which utilized a uniform methodology for blood pressure measurement can further support the findings of this systematic review.

Efficacy and safety of renal denervation for resistant hypertension:A systematic review and meta-analysis

Background Renal denervation has a tortuous history.Significant reductions in blood pressure following denervation of the renal artery were observed in early trials,but subsequent denervation under sham surgery was found to be neutral.Methods This study was performed according to search results by CNKI,WANFANG DATA,EMBASE database,Pubmed,Medline,the Cochrane Central Register of Controlled Trials,Clinicaltrials.gov,and World Health Organization International Clinical Trials Registry Platform from database inception to June 20,2019.For continuous outcomes,heterogeneity were assessed by Cochran’s Q test and random-effect models weighted for the inverse of the variance.Dichotomous data were analyzed using relative risk(RR)with 95%CIs.Safety was assessed by assessing the risk of major adverse events from stratified contingency tables.Results 10 randomized controlled trials with a total of 1323 individuals were included in the quantitative analysis.Pooled analyses indicated that renal denervation was associated with a significantly greater reduction of office systolic blood pressure[mean difference(MD):-5.61 mm Hg,95%CI:-9.03 to-2.19,Z=3.21,P=0.0001]and 24-hour systolic blood pressure(MD:-4.40 mmHg,95%CI:-14.03 to-3.83,Z=5.09,P<0.00001)than controls.Renal denervation was not associated with an increased risk of major adverse events(RR:1.12,95%CI:0.72 to 1.64,Z=0.66,P=0.51),and estimated glomerular filtration rate(e GFR)[MD:0.35 mL/(min·1.73 m2),95%CI:-2.05 to2.74,Z=0.28,P=0.78]from baseline to 6 months is statistically insignificant with significant heterogeneity.Conclusions In selected resistant hypertension patients maintained on antihypertensive drugs,renal denervation with the SYMPLICITY systems did significantly decrease blood pressure.Renal denervation was not associated with an increased risk of major adverse events.

Device-Based Treatment in Hypertension:At the Forefront of Renal Denervation

Percutaneous renal denervation is a novel device therapy that modifies the circulatory regulatory system and has received considerable attention recently.This treatment partially blocks the renal sympathetic nervous system,which is an organ-connecting pathway between the brain and the kidney.Denervation techniques currently under clinical investigation include radiofrequency,ultrasonic,and chemical ablation with alcohol,all of which are executed through transcatheter access to the renal artery.All recently published randomized sham-controlled trials have shown a clear antihypertensive effect of renal denervation over 24 hours,including during the nighttime and early morning.This treatment has promise in the management of poorly controlled hypertension as well as in the prevention of the development or aggravation of arrhythmias and heart failure.

Computed tomography-guided chemical renal sympathetic nerve modulation in the treatment of resistant hypertension: A case report

BACKGROUND Resistant hypertension(RH)has always been a difficult problem in clinical diagnosis and treatment.At present,there is no recognized safe and effective minimally invasive treatment.CASE SUMMARY An 80-year-old woman was admitted to hospital due to trigeminal neuralgia(TN).The patient had a history of RH for more than 10 years and her blood pressure(BP)was not well-controlled.Before the treatment for TN,we decided to perform chemical renal sympathetic denervation with ethanol in the Pain Department of our hospital.One year after the operation,she stopped taking antihypertensive drugs,and her BP was satisfactorily controlled within 4 years after surgery.CONCLUSION Computed tomography-guided chemical renal sympathetic modulation may be a feasible method for the treatment of RH.

肾脏去神经技术:历史,现状和前景（英文）

Renal denervation is a new technique approved effective for resistant-hypertension treatment.The common renal denervation system consists of a generator and a flexible catheter.During this minimally invasive procedure,the interventionalist uses a steerable catheter with a radio frequency(RF)energy electrode tip.The RF energy is delivered to the renal artery via standard femoral artery access.A series of 2-minute ablation are delivered in each renal artery to distroy the nerves system.The procedure does not involve a permanent device implant.By deactivating the renal nerves,and therefore reducing sympathetic nerve transmission,a significant and reliable reduction in blood pressure could be achieved.In this review,potential complications and future sights of renal denervation are also discussed.

Renal sympathetic denervation reduces left ventricular hypertrophy and improves cardiac function in patients with resistant hypertension

This study investigated the effect of catheter-based renal sympathetic denervation （RD） on left ventricular hypertrophy （LVH） and systolic and diastolic function in patients with resistant hypertension. LVH and diastolic dysfunction are associated with elevated sympathetic activity and increased morbidity and mortality. The effect of RD on LVH and LV function is unclear

Biophysical Substantiation of a Surgical Method of Treatment of a Primary Arterial Hypertension

It is shown that flow of a blood in a passive elastic tube essentially unstable process accompanying with a flutter of a stream. Biophysical principles of neuroreflex regulation of an arterial bloodstream in cardiovascular system are considered. It is shown that this regulation has dual-purpose character： reduction of the hydraulic resistance and maintenance stable no flutter stream of blood. The reasons of a primary arterial hypertension occurrence, and also some accompanying it physical and physiological phenomena are considered. The surgical method of treatment of the primary arterial hypertension, connected with denervation of renal arteries is substantiated.

Efficacy of regional renal nerve blockade in patients with chronic refractory heart failure

Background Increased renal sympathetic nerve activity can result in diuretic resistance in patients with chronic congestive heart failure. We investigated the effect of regional renal nerve blockade on the patients with chronic refractory heart failure and diuretic resistance. Methods Eighteen patients with chronic refractory heart failure were enrolled （mean age （64＋11） years）. The patients were randomly divided into two groups （renal nerve blockade group and standard therapy group, n=9 each）. Renal nerve blockade was performed by percutaneous injection of local anaesthetic under computed tomographic guidance. Heart rate, mean arterial blood pressure, plasma and urine electrolytes, neurohormones, factional excretion of sodium （FENa）, 24-hour urine volume were monitored at baseline and the first 24 hours after therapy. Dyspnea and oedema were also evaluated. The major adverse cardiovascular events （MACE）, plasma brain natriuretic peptide （BNP） level and left ventricular ejection fraction （LVEF） were compared between the two groups during the 3-12 months follow-up period. Results No complication was observed during the acute phase of renal nerve blockade. After renal nerve blockade, the 24-hour urine volume and FENa were significantly increased, while the level of plasma rennin, angiotensin II, aldosterone BNP and atrial natriuretic peptide as well as dyspnea and oedema were significantly reduced in renal nerve blockade group compared with baseline and standard therapy group. During three to 12 months of follow-up, the rate of MACE and plasma BNP level were significantly lower, while LVEF was significantly higher in renal nerve blockade group than those in standard therapy group. Conclusion Regional renal nerve blockade may be a safe and effective treatment for patients with chronic refractory heart failure.