Renal Denervation For Resistant Hypertension Research Articles

Renal Denervation for Resistant Hypertension: Where Do We Stand?

To review the data about the use of renal denervation (RDN), a minimally invasive surgery, for resistant hypertension (RH) and to provide practical guidance for practitioners who are establishing an RDN service. RDN can selectively ablate renal sympathetic nerve fibres, block the transmission of nerve impulses between central sympathetic nerve and kidney, to control blood pressure to as a novel promising non-drug treatment option for RH. At present, there are many researches on the treatment of RH by RDN, but there are some controversies. This review summarises and critically examines the evidence for RDN in the treatment of RH and identifies areas for future research. With the development of RDN, the continuous innovation of RDN technology and methods, the development about better evaluating the real-time success of RDN and the improvement for identifying individuals who are most likely to benefit from RDN will ultimately determine whether RDN represents a feasible way to manage RH in the future.

4-3RENAL DENERVATION FOR RESISTANT HYPERTENSION POST-SIMPLICITY-3 HTN TRIAL: META-ANALYSIS AND SYSTEMATIC REVIEW

Background: Following the result from SIMPLICITY-3 trial that failed to show the benefit of renal denervation over sham control, the interest on renal denervation had fallen into hibernation. However, there were some authors indicated that SIMPLICITY-3 trial result seemed to have major problems regarding incomplete denervation that led experts to researched and carefully designed studies regarding renal denervation. Since then, there was three carefully-designed, sham-controlled studies published about the issue. However, there was no published meta-analysis on randomized trials after SIMPLICITY-3 era. We aimed to conduct a meta-analysis of RCTs to determine the effect of renal denervation in resistant hypertension. Methods: A search on MEDLINE and EMBASE was conducted in January 2020. Randomized clinical studies comparing renal denervation and sham-controlled trial published after SIMPLICITY-3 trial were included for this meta-analysis. Study selection: only fully published RCT and abstracts of RCT comparing renal denervation and sham control for resistant hypertension published after SIMPLICITY-3 trial was included. Studies which were duplicated and non-randomized were excluded. Results: The analysis included 149 patients from 3 trials with a duration of follow up of 2–6 months. The reduction in 24-h ambulatory SBP was significantly greater in the renal denervation group compared to the sham procedure (WMD −4.74 mmHg, 95% CI −6.5, −2.99; p < 0,001). There was also significant reduction in 24-h DBP (WMD −3.11 mmHg, 95% CI −3.98, −2.23; p < 0,001), office SBP (WMD −7.1 mmHg, 95% CI −9.12, −5.08; p < 0,001), and office DBP (WMD −4,63 mmHg, 95% CI −5.98, −3.28; p < 0,001). Conclusion: Following SIMPLICITY-3 trial, there were positive results regarding renal denervation on resistant hypertension. Renal denervation significantly reduced blood pressure compared to sham control. Our meta-analysis underscores the importance of conducting new well-designed studies to confirm our observed results.

Activated double-negative T cells (CD3+CD4−CD8−HLA-DR+) define response to renal denervation for resistant hypertension

PurposeTo explore the cellular immune response of patients with resistant hypertension treated with renal denervation (RDN). Methods and resultsTwenty-three patients were included and blood samples were obtained in six timings, pre and post procedure. Response was evaluated at six-months and one year and was observed in 69.6% and 82.6% of patients, respectively. Absolute values of HLA-DR+ double negative (DN) T cells were significantly lower in the group of ‘responders’ at one year, and interaction between the timings were found in three T cell subsets (T CD4, T CD8 and naïve T CD8 cells), with the ‘responders’ tending to present with lower absolute values and little inter-timing variation. Conclusions‘Responders’ significantly present with lower absolute values of activated DN T cells and have lower and more stable values of total T CD8+, CD4+, and naïve T CD8+ cells. These cell types may be able to predict response to RDN.

Controversies in the management of patients with arterial hypertension

Every 5 to 6 years, international and national guidelines provide updated recommendations for the standard management of hypertension in adults. Thus, within the last 18 months, societies from Europe (European Society of Cardiology and European Society of Hypertension), America (American College of Cardiology and American Heart Association), and Great Britain (National Institute for Health and Care Excellence) published their new guidelines. Despite the fact that all of them are supposedly based on the most recent clinical evidence, there are always some discrepancies between recommendations due to different interpretation of clinical trials. The purpose of the present review is to discuss 6 issues that have generated some controversies, namely, the definition of hypertension, identification of patients who should be treated, target blood pressure, pertinence of reducing salt intake, and the role of renal denervation in resistant hypertension.

Renal Denervation for Resistant Hypertension in the contemporary era: A Systematic Review and Meta-analysis

Renal denervation (RDN) is a catheter-based ablation procedure designed to treat resistant hypertension (RH). The objective of our study is to determine the effect of RDN on blood pressure and renal function in patients with RH in comparison to medical therapy alone. We performed an extensive literature search for randomized control trials (RCT) reporting office and 24 hr. blood pressure changes and estimated glomerular filtration rate (eGFR) at baseline and 6 months. We calculated a weighted standardized mean difference of blood pressure and renal outcomes between RDN and control groups using random effects models. Our search yielded 608 studies of which we included 15 studies for the final analysis. A total of 857 patients were treated with RDN and 616 patients treated with medical therapy ± sham procedure. Only 5 studies were double-blinded RCT with sham control. The adjusted standardized mean difference in the change in office based systolic and diastolic pressures (p = 0.18; p = 0.14); 24 hr. systolic and diastolic pressures (p = 0.20; p = 0.18); and eGFR (p = 0.20) from baseline to 6 months is statistically insignificant with significant heterogeneity. Subgroup analysis showed that among sham controlled trials, 24 hr. systolic blood pressure showed a modest but statistically significant benefit favoring renal denervation in patients with RH. Our meta-analysis of 15 RCTs showed no significant benefit of RDN on blood pressure control in patients with resistant hypertension. Subgroup analysis of sham control studies showed a modest benefit in 24 hr. systolic blood pressure at 6 months with RDN.

A17651 Renal denervation for resistant hypertension in patients less than 65-year-old

Objectives: To investigate the safety and mid-term efficacy of renal denervation (RDN) in less than 65-year-old Chinese patients with resistant hypertension. Methods: In the prospective cohort study, the patients with resistant hypertension were continuously enrolled to undergo RDN between November 2012 and November 2014 using LEPU single-electrode ablation catheter. The primary effectiveness endpoints were reductions in office blood pressure and 24-hour ambulatory blood pressure (24h-ABP) at six months. The primary safety endpoint was the incidence of major adverse event through 6 months. Results: A total of 50 consecutive patients, aged between 26 and 62 (41.9 ± 10.6) years old, were enrolled, in which 18 (36.0%) were female. At six months after surgery, the office BP and 24-h ABP were separately reduced by 23.7 ± 14.5/11.5 ± 7.9 mmHg and 11.1 ± 8.5/7.1 ± 6.2 mmHg, with the reduction of the number of antihypertensive agents from 4.0 (4.0∼4.0) at baseline to 4.0 (3.0∼4.0) (all P < 0.01). There is no significant change of renal function (P > 0.05) and no major adverse events occurred. Only one patient suffered from femoral artery pseudoaneurysm with no sequelae. Conclusion: RDN seems to be safe and effective in lowering BP in the less than 65-year-old Chinese cohort with resistant hypertension.

Regression of organ damage following renal denervation in resistant hypertension: a meta-analysis.

Prospective observational studies have suggested that renal denervation (RDN) is associated with target organ damage (TOD) regression. Our aim is to review and meta-analyze the available evidence for the effect of RDN on TOD. We searched literature for studies with eligible content and performed random-effect meta-analyses for the following outcomes: left ventricular mass index (LVMI), left atrial volume index (LAVI), E to A wave velocities of trans-mitral inflow (E/A) and E wave velocity to Em velocity from tissue Doppler imaging (E/Em), central augmentation index (AIx) and carotid-femoral pulse wave velocity (PWV). Seventeen studies (n = 698 patients) were incorporated in the present meta-analysis. RDN led to a regression of LVMI by 14.17 g/m (95% CI -18.33 to -10.01, P < 0.001) and by 4.75 g/m (95% CI -7.83 to -1.67, P = 0.003) for echocardiography and cardiac magnetic resonance, respectively. The pooled effect of RDN to E/A was not significant [0.04 (95% CI -0.03 to 0.12, P = 0.252)], whereas a decline of E/Em [-0.73 (95% CI -1.38 to -0.08, P = 0.03)] was observed. The pooled effect to LAVI [-1.67 ml/m (95% CI -4.60 to 1.27, P = 0.266)] reached statistical significance only in sensitivity analysis. RDN had beneficial effects in both AIx [-7.05 (95% CI -9.12 to -4.98, P < 0.001)] and PWV [1.54 m/s (95% CI -2.16 to -0.92, P < 0.001)]. Metaregression analysis revealed an independent effect of RDN on TOD regarding baseline blood pressure and blood pressure reduction. Catheter-based RDN can favorably affect TOD.

Renal Denervation in Resistant Hypertension and Obstructive Sleep Apnea

It has been postulated that catheter-based renal denervation (RDN) may lower blood pressure (BP) and improve severity of obstructive sleep apnea (OSA) in resistant hypertensive patients. The aim of our study (NCT01366625) was to investigate in a prospective randomized trial the effect of RDN on BP and clinical course of OSA. Sixty patients with true resistant hypertension coexisting with moderate-to-severe OSA (apnea/hypopnea index, ≥15) were randomly allocated to RDN group (30 patients) and to control group (30 patients). The primary end point was reduction in office systolic BP at 3 months. Secondary end points included reduction in diastolic office and ambulatory BP, change in apnea/hypopnea index and biochemical measurements at 3 months, and change in echocardiographic measurements at 6 months. There were no differences in clinical characteristics between the groups. At 3 months in the RDN group, both office and ambulatory BP were significantly reduced, and a significant decrease in OSA severity (apnea/hypopnea index, 39.4 versus 31.2 events per hour; P =0.015) was observed. Between-group difference in apnea/hypopnea index change was significant at 0.05. At 6 months in the RDN group, reductions in office and ambulatory BP were sustained and were accompanied by significant improvement in echocardiographic measures of global longitudinal strain. There were no differences in metabolic variables in follow-up in both groups. In a randomized controlled trial, RDN lowered both office and ambulatory BP in patients with resistant hypertension and OSA. This was accompanied by improvement of the clinical severity of OSA. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01366625.

Sténose de l’artère rénale à distance d’une dénervation rénale pour HTA résistante

The onset of renal artery stenosis following a renal denervation is rare and occurs in the first few months after renal denervation. We report the onset of renal artery stenosis a long time after the renal denervation for resistant hypertension. This is a 74 year-old patient who stopped smoking in 1980 and who was treated for dyslipidemia with a revascularized coronary artery disease in 2011, a well-stabilized peripheral arterial disease since 2001, a stable asymptomatic carotid atheroma and a good kidney function. His hypertension known since 1995 became resistant. After the control of renal arteries by angio-CT scan, he had a renal denervation in October 2012. His blood pressure decreased 3 months later confirmed by self-blood pressure monitoring (SBPM) and ambulatory blood pressure monitoring (ABPM) with a CT scan with a non-significant renal artery stenosis in January 2014. He remained normotensive under treatment until July 2015 but his hypertension became uncontrolled at the end of 2015 then resistant and severe confirmed by SBPM in April 2017, despite a 5-drug antihypertensive treatment associated to atorvastatin and clopidogrel confirmed by SBPM in April 2017. A left post-ostial renal artery stenosis with decrease in size of left kidney and cortex as compared to 2011 was detected at CT and treated by angioplasty. It was associated with a rapid decrease in blood pressure but unfortunately a new increase related to a restenosis occurred at the end of 2017, which justified a new angioplasty. Discussion about the etiology and the management of this renal post-denervation late stenosis.

Effectiveness of Renal Denervation in Resistant Hypertension: A Meta-Analysis of 11 Controlled Studies.

Early uncontrolled studies reported large blood pressure reductions in subjects with resistant hypertension treated with renal denervation, however these results were not confirmed in several of the latest publications. The aim of the current study was to evaluate the effectiveness of RDN in controlled studies comparing RDN to either a sham procedure or to medical therapy. Only controlled studies were included in the analysis. Both the unadjusted and control-adjusted BP changes were calculated. We identified 11 publications of which only 3 were double-blinded RCTs with a sham control, while 8 were open label studies where the control group was treated with medical therapy. Only 2 studies assessed adherence to medical therapy with robust methodologies. Office BP reduction (- 18/8mmHg) significantly overestimated ABPM change (- 9/- 5mmHg), with high heterogeneity between the included studies. When the treatment effect was adjusted for the BP change in the control group, BP changes became non significant (ABPM: - 1.8 for systolic BP [95% CI - 4.5 to 0.9] and - 0.6 for diastolic BP [95% CI - 2.3 to 1.2]). These results were confirmed when only the sham-controlled studies were analysed. In spite of promising results in early reports, renal denervation fails to show superiority to a sham procedure or to medical therapy in recently published controlled studies. Lack of a sham control in most publications and heterogeneity in assessment of treatment adherence may account for part the variability reported in the studies. Renal denervation fails to show superiority to a sham procedure or to medical therapy in recently published controlled studies.

Salt intake and blood pressure response to percutaneous renal denervation in resistant hypertension.

The effect of lowering sympathetic nerve activity by renal denervation (RDN) is highly variable. With the exception of office systolic blood pressure (BP), predictors of the BP-lowering effect have not been identified. Because dietary sodium intake influences sympathetic drive, and, conversely, sympathetic activity influences salt sensitivity in hypertension, we investigated 24-hour urinary sodium excretion in participants of the SYMPATHY trial. SYMPATHY investigated RDN in patients with resistant hypertension. Both 24-hour ambulatory and office BP measurements were end points. No relationship was found for baseline sodium excretion and change in BP 6months after RDN in multivariable-adjusted regression analysis. Change in the salt intake-measured BP relationships at 6months vs baseline was used as a measure for salt sensitivity. BP was 8mmHg lower with similar salt intake after RDN, suggesting a decrease in salt sensitivity. However, the change was similar in the control group, and thus not attributable to RDN.

Sympathetic nerve traffic and blood pressure changes after bilateral renal denervation in resistant hypertension: a time-integrated analysis.

Renal denervation reduces blood pressure (BP) and sympathetic drive in experimental animal models, but the effect of this intervention on sympathetic activity in patients with treatment-resistant hypertension is still unclear. In an incident series of 29 patients with treatment-resistant hypertension, we performed serial measurements (n = 123) of muscle sympathetic nerve activity (MSNA, microneurography) and standardized BP measurements. Data were analysed by mixed linear modelling (MLM) and by regression analysis of time-integrated changes of both MSNA and synchronous, standardized (in-lab) BP measurements. Bilateral renal denervation was accompanied by a marked reduction in MSNA (P = 0.01 by MLM), which was parallelled by a reduction in systolic (from 175 ± 14 to 156 ± 16 mmHg) and, to a lesser extent, in diastolic (from 96 ± 12 to 87 ± 6 mmHg) BP over time. Neither systolic nor diastolic BP associated to a significant extent with corrected MSNA (MSNAC) in the MLM analysis (systolic BP versus MSNAC: β = -0.08, P = 0.08; diastolic BP versus MSNAC: β = -0.007, P = 0.75). However, the study of time-integrated changes in MSNA and BP showed a robust association between proportional changes in MSNA over time and simultaneous changes in systolic and diastolic BP (β = 0.61, P < 0.001 and β = 0.37 P < 0.05). Time-integrated changes in MSNAC and BP after bilateral renal denervation document a close link between the sympathetic activity and BP responses to this procedure. These findings further strengthen the relevance of the sympathetic nervous system both in the pathophysiology of resistant hypertension and in the BP-lowering effect of the procedure.

Almanac 2013: novel non-coronary cardiac interventions.

Recent innovations in interventional cardiology have dramatically expanded the therapeutic options for patients with cardiac conditions. Interventional cardiology is no longer limited to the treatment of coronary artery disease but allows also treatment of valvular disease, stroke prevention, hypertension, etc. One of the most important new treatment options is the percutaneous treatment for aortic valve stenosis (transcatheter aortic valve implantation), since aortic valve disease is a rather common problem in elderly patients, with many of them at high risk for surgery. Similarly, mitral regurgitation is often associated with comorbidities which make surgery high risk. The MitraClip is a promising percutaneous alternative to surgical valve repair or replacement. Other procedures discussed in this review are the percutaneous left atrial appendage closure as a non-pharmacologic therapy to prevent strokes, and renal denervation for resistant hypertension. This review explains the basic principles of these procedures, the most important clinical evidence, and also provides additional recent clinical data on each of them.

Sham or no sham control: that is the question in trials of renal denervation for resistant hypertension. A systematic meta-analysis

Background: Studies of renal denervation (RDN) in patients with apparent treatment resistant hypertension have been hampered by a number of patient and physician related confounders on blood pressure (BP) including poor drug adherence. It remains uncertain whether RDN lowers BP. We aimed to investigate whether the use of sham control is essential in RDN studies or whether systematic use of 24-hour ambulatory BP provides enough information thereby making an invasive sham control redundant.Methods: We meta-analyzed randomized controlled trials of the BP response to RDN on top of continued or optimized antihypertensive drugs in patients with resistant hypertension. On top of the randomized trials reviewed earlier, we additionally included three studies, one conducted in Spain (24 patients, RDN vs. spironolactone), one conducted in Denmark (69 patients, sham controlled) and one conducted in Netherlands (139 patients, RDN vs. continued treatment). We analyzed 24-hour ambulatory BP in 3 sham controlled studies vs. 7 no sham controlled studies.Results: The updated meta-analysis of 10 studies showed 3.6 mmHg (p = .45) and 1.0 mmHg (p = .54) reductions in office and in 24-hour systolic BP, respectively. Meta-analysis of 24-hour systolic BP in the 3 sham-controlled studies showed a reduction of 2.18 mmHg (95% confidence intervals (CIs) −4.70 to 0.33 mmHg, n = 396 vs. 230, p = .07). For the 7 no sham controlled studies there was no difference in 24-hour systolic BP (+0.38 mmHg; 95% CIs −5.29 to 6.04 mmHg, n = 215 vs. 245, p = .90). The test for sub-group heterogeneity showed no significant interaction (p = .69). Removing one trial at a time produced confirmatory results.Conclusion: The overall meta-analysis of 10 randomized and controlled studies showed no significant effect on BP of RDN in resistant hypertension. Moreover, our analysis does not support the use of sham control but rather suggests extensive use of 24-hour ambulatory BP in studies of RDN in resistant hypertension

Catheter-Based Renal Denervation for Resistant Hypertension: Will It Ever Be Ready for "Prime Time"?

The year 2014 was a turning point for the field of renal denervation (RDN) and its potential use to treat resistant hypertension. Tremendous enthusiasm shifted to sober reflection on the efficacy of a technology once touted as the cure to resistant hypertension. The following review highlights 2 major questions: First, does catheter-based RDN lower blood pressure and, second, will RDN using catheter-directed therapy for the treatment of resistant hypertension ever become more than an investigational technology.

Renal Sympathetic Hyperactivity in Hypertension: True or False?

Increased renal norepinephrine spillover, observed by using isotope-dilution method, is thought to indicate renal sympathetic hyperactivity and to play a crucial role in hypertension. However, SYMPLICITY HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension), the first randomized sham-controlled trial, failed to show a benefit of renal denervation for resistant hypertension.1 This raises the issue of whether the sympathetic hyperactivity hypothesis is true. In a recent issue of Circulation Research , Grassi et al2 have emphasized the presence and importance of sympathetic hyperactivity in hypertension, primarily based on the results of isotope-dilution studies. However, the isotope-dilution method cannot exclude the involvement of intraorgan platelet release of norepinephrine. We would argue that platelet norepinephrine release, rather than sympathetic nervous system alterations, may be the cause of increased norepinephrine spillover in hypertension for …

Renal Denervation for Resistant Hypertension Fails to Improve Insulin Resistance as Assessed by Hyperinsulinemic-Euglycemic Step Clamp.

We assessed whether insulin sensitivity improved after renal denervation (RDN) for resistant hypertension. Twenty-three patients underwent a two-step hyperinsulinemic-euglycemic clamp (HEC) with glucose tracer and labeled glucose infusion and oral glucose tolerance test (OGTT) before and 6 months after RDN. Eighteen patients had metabolic syndrome at baseline. Blood pressure declined significantly after RDN, whereas mean (SD) fasting plasma glucose concentration (5.9 ± 0.7 mmol/L), median (minimum-maximum) insulin concentration (254 pmol/L [88-797 pmol/L]), and median C-peptide concentration (2.4 nmol/L [0.9-5.7 nmol/L]) remained unchanged. Endogenous glucose release during HEC was less suppressed after RDN, suggesting a slight decrease in hepatic insulin sensitivity. During high-dose insulin infusion, whole-body glucose disposal was low and remained unchanged after RDN, indicating persistent peripheral insulin resistance (IR). Area under the curve for 0-120 min for glucose and insulin during OGTT, Quantitative Insulin Sensitivity Check Index, Simple Index Assessing Insulin Sensitivity Oral Glucose Tolerance, and HOMA-IR were high, and did not improve after RDN. Despite a significant decrease in blood pressure, neither peripheral nor hepatic insulin sensitivity improved 6 months after RDN treatment in this group of insulin-resistant patients without diabetes and with resistant hypertension, as measured with gold standard methods.

GW26-e2233 Noninvasive Renal Denervation for Resistant Hypertension Using High-intensity Focused Ultrasound

GW26-e2233 Noninvasive Renal Denervation for Resistant Hypertension Using High-intensity Focused Ultrasound

Spironolactone for resistant hypertension—hard to resist?

Spironolactone for resistant hypertension—hard to resist?

Catheter-based renal denervation for resistant hypertension: Twenty-four month results of the EnligHTN™ I first-in-human study using a multi-electrode ablation system

BackgroundLong term safety and efficacy data of multi-electrode ablation system for renal denervation (RDN) in patients with drug resistant hypertension (dRHT) are limited. Methods and resultsWe studied 46 patients (age: 60±10years, 4.7±1.0 antihypertensive drugs) with drug resistant hypertension (dRHT). Reduction in office BP at 24months from baseline was −29/−13mmHg, while the reduction in 24-hour ambulatory BP and in home BP at 24months were −13/−7mmHg and −11/−6mmHg respectively (p<0.05 for all). A correlation analysis revealed that baseline office and ambulatory BP were related to the extent of office and ambulatory BP drop. Apart from higher body mass index (33.3±4.7 vs 29.5±6.2kg/m2, p<0.05), there were no differences in patients that were RDN responders defined as ≥10mmHg decrease (74%, n=34) compared to non-responders. Stepwise logistic regression analysis revealed no prognosticators of RDN response (p=NS for all). At 24months there were no new serious device or procedure related adverse events. ConclusionsThe EnligHTN I study shows that the multi-electrode ablation system provides a safe method of RDN in dRHT accompanied by a clinically relevant and sustained BP reduction.