Renal Denervation For Hypertension Research Articles

Effects of Catheter-Based Renal Denervation in Hypertension: A Systematic Review and Meta-Analysis.

Several sham-controlled trials have investigated the efficacy and safety of catheter-based renal denervation (RDN) with mixed outcomes. We aimed to perform a comprehensive meta-analysis of all randomized, sham-controlled trials investigating RDN with first- and second-generation devices in hypertension. We searched MEDLINE and the Cochrane Library for eligible trials. Outcomes included both efficacy (24-hour and office systolic [SBP] and diastolic blood pressure [DBP]) and safety (all-cause death, vascular complication, renal artery stenosis >70%, hypertensive crisis) of RDN. We performed a study-level, pairwise, random-effects meta-analysis of the summary data. Ten trials comprising 2478 patients with hypertension while being either off or on treatment were included. Compared with sham, RDN reduced 24-hour and office systolic blood pressure by 4.4 mm Hg (95% CI, 2.7 to 6.1; P<0.00001) and 6.6 mm Hg (95% CI, 3.6 to 9.7; P<0.0001), respectively. The 24-hour and office diastolic blood pressure paralleled these findings (-2.6 mm Hg [95% CI, -3.6 to -1.5]; P<0.00001; -3.5 mm Hg [95% CI, -5.4 to -1.6]; P=0.0003). There was no difference in 24-hour and office systolic blood pressure reduction between trials with and without concomitant antihypertensive medication (P for interaction, 0.62 and 0.73, respectively). There was no relevant difference in vascular complications (odds ratio, 1.69 [95% CI, 0.57 to 5.0]; P=0.34), renal artery stenosis (odds ratio, 1.50 [95% CI, 0.06 to 36.97]; P=0.80), hypertensive crisis (odds ratio, 0.65 [95% CI, 0.30 to 1.38]; P=0.26), and all-cause death (odds ratio, 1.76 [95% CI, 0.34 to 9.20]; P=0.50) between RDN and sham groups. Change of renal function based on estimated glomerular filtration rate was comparable between groups (P for interaction, 0.84). There was significant heterogeneity between trials. RDN safely reduces ambulatory and office systolic blood pressure/diastolic blood pressure versus a sham procedure in the presence and absence of antihypertensive medication.

Effects of catheter-based renal denervation in hypertension: a systematic review and meta-analysis.

Several sham-controlled trials have investigated the efficacy and safety of catheter-based renal denervation (RDN) with mixed outcomes. To perform a comprehensive meta-analysis of all randomized, sham-controlled trials investigating RDN with first- and second-generation devices in hypertension. We searched MEDLINE and Cochrane Library for eligible trials. Outcomes included both efficacy (24-hour and office systolic [SBP] and diastolic blood pressure [DBP]) and safety (all-cause death, vascular complication, renal artery stenosis >70%, hypertensive crisis) of RDN. We performed a study-level, pairwise, random-effects meta-analysis of the summary data. Ten trials comprising 2,478 patients with hypertension while being either off- or on-treatment were included. Compared with sham, RDN reduced 24-hour and office systolic BP by 4.4 mmHg (95%CI -6.1, -2.7, p<0.00001) and 6.6 mmHg (95%CI -9.7, -3.6, p<0.0001), respectively. The 24-hour and office diastolic BP paralleled these findings (-2.6 mmHg, 95%CI - 3.6, -1.5, p<0.00001; -3.5 mmHg, 95%CI -5.4, -1.6, p=0.0003). There was no difference in 24-hour and office SBP reduction between trials with and without concomitant antihypertensive medication (p for interaction 0.62 and 0.73, respectively). There was no relevant difference concerning vascular complications (OR 1.69, 95%CI 0.57-5.0, p=0.34), renal artery stenosis (OR 1.50, 95%CI 0.06-36.97, p=0.80), hypertensive crisis (OR 0.65, 95%CI 0.30-1.38, p=0.26) and all-cause death (OR 1.76, 95%CI 0.34-9.20, p=0.50) between RDN and sham groups. Change of renal function based on eGFR was comparable between groups (p for interaction 0.84). There was significant heterogeneity between trials. RDN safely reduces ambulatory and office SBP/DBP vs. a sham procedure in the presence and absence of antihypertensive medication. What is new?Several sham-controlled trials have investigated the efficacy and safety of catheter-based renal denervation (RDN) with mixed outcomes.This comprehensive meta-analysis comprising 2,478 patients shows that irrespective of the utilized method (radiofrequency-, ultrasound-or alcohol-mediated), renal denervation effectively reduced ambulatory and office systolic blood pressure.Renal denervation exhibited no additional risk concerning vascular injury or renal function impairment.What are the clinical implications?This meta-analysis supports current guidelines/consensus statements that renal denervation represents an additive treatment option in carefully selected patients with uncontrolled hypertension.

Ultra-long-term efficacy and safety of catheter-based renal denervation in resistant hypertension: 10-year follow-up outcomes

BackgroundRandomized sham-controlled trials have confirmed the efficacy and safety of catheter-based renal denervation in hypertension. Data on the very long-term effects of renal denervation are scarce.AimsThis study evaluates the 10-year safety and efficacy of renal denervation in resistant hypertension.MethodsThis prospective single-center study included patients with resistant hypertension undergoing radio-frequency renal denervation between 2010 and 2012. Office blood pressure, 24-h ambulatory blood pressure, antihypertensive medication, color duplex sonography, and renal function were assessed after 1-, 2- and 10-years.ResultsThirty-nine patients completed the 10-year follow-up (mean follow-up duration 9.4 ± 0.7 years). Baseline office and 24-h ambulatory systolic blood pressure were 164 ± 23 mmHg and 153 ± 16 mmHg, respectively. After 10 years, 24-h ambulatory and office systolic blood pressure were reduced by 16 ± 17 mmHg (P < 0.001) and 14 ± 23 mmHg (P = 0.001), respectively. The number of antihypertensive drugs remained unchanged from 4.9 ± 1.4 to 4.5 ± 1.2 drugs (P = 0.087). The estimated glomerular filtration rate declined within the expected range from 69 (95% CI 63 to 74) to 60 mL/min/1.73m2 (95% CI 53 to 68; P < 0.001) through 10-year follow-up. Three renal artery interventions were documented for progression of pre-existing renal artery stenosis in two patients and one patient with new-onset renal artery stenosis. No other adverse events were observed during the follow-up.ConclusionRenal denervation was safe and sustainedly reduced ambulatory and office blood pressure out to 10 years in patients with resistant hypertension.Graphical abstractLeft panel, Change in 24-h and office SBP. Right panel, eGFR over time. SBP, systolic blood pressure; eGFR, estimated glomerular filtration rate.

Recent Advances in Renal Denervation

Abstract Renal sympathetic nerves contribute to the occurrence and progression of cardiovascular diseases. However, the role of renal denervation in cardiovascular diseases is questionable because clinical studies of renal denervation in hypertension are inconsistent. The renal artery nerves contain not only the sympathetic afferent but also efferent nerve fibers. Incorrect ablation position may lead to an opposite outcome. Some patients or even healthy individuals exhibit renal artery abnormalities. The accurate ablation of the renal sympathetic nerves depends on complete anatomy and precise positioning. Fortunately, the current renal artery stimulation technology can screen a section of renal sympathetic nerves. Renal denervation methods such as ultrasound and microwave ensure proper peripheral ablation. Shorter ablation time, less endothelial damage, precise sympathetic nerve positioning, and complete nerve ablation are the future prospects. This review discusses the existing evidence on renal artery and renal sympathetic nerve anatomy, renal denervation techniques, and future trends.

SCAI Position Statement on Renal Denervation for Hypertension: Patient Selection, Operator Competence, Training and Techniques, and Organizational Recommendations.

SCAI Position Statement on Renal Denervation for Hypertension: Patient Selection, Operator Competence, Training and Techniques, and Organizational Recommendations.

Renal denervation in hypertension: An updated meta-analysis of the randomized controlled trials.

Radiofrequency or ultrasound renal denervation (RDN) has shown conflicting results when used as an adjunctive option for hypertension management in randomized controlled trials (RCTs). We searched Pubmed, MEDLINE, and other online databases for RCTs comparing RDN versus sham-control procedures in patients with uncontrolled or resistant hypertension. The endpoints of interest were 24-h ambulatory (AMB) blood pressure (BP), daytime AMB BP, and office BP. We performed a random-effects meta-analysis using the inverse variance method to estimate mean difference (MD) with a 95% confidence interval (CI). Nine studies with 1643 patients were included in the final analysis. The mean follow-up was 5 months. As compared with the sham-controlled group, RDN was associated with a significant decrease in 24-h AMB BP (systolic [MD -4.20; 95% CI -5.36 to -3.03; p < 0.00001], diastolic [-2.38; -3.42 to -1.35]), and daytime AMB BP (systolic: -5.11; -6.75 to -3.47, diastolic: -2.88; -3.91 to -1.85). Similarly, office BP was reduced with RDN (systolic: -5.46; -7.12 to -3.81; diastolic: -3.17; -4.23 to -2.12) when compared with placebo. Our meta-analysis shows that RDN is associated with a significant reduction in the 24-h AMB BP, daytime AMB BP, and office BP.

The effect of catheter-based sham renal denervation in hypertension: systematic review and meta-analysis

BackgroundRenal denervation (RDN) has emerged in recent years as a possible treatment for hypertension. The first sham-controlled trial showed a small magnitude and non-significant in the blood pressure (BP) lowering effect, also due to a substantial decrease of BP in sham arm. Considering this, we aimed to quantify the magnitude of BP decrease within the sham arm of Randomized Controlled Trials (RCT) with RDN in patients with hypertension.MethodsElectronic databases were searched since inception until January 2022 for randomized sham-controlled trials which assessed the efficacy in lowering BP of the sham intervention for catheter-based RDN in adult patients with hypertension. The outcomes were change in ambulatory/office systolic and diastolic BP.ResultsA total of 9 RCT were included in the analysis enrolling a total of 674 patients. Sham intervention showed a decrease in all evaluated outcomes. Office systolic BP had a reduction of -5.52 mmHg [95%CI -7.91, -3.13] and office diastolic BP of -2.13 mmHg [95%CI -3.08, -1.17]. Sham procedure for RDN also showed a reduction of -3.41 mmHg [95%CI -5.08, -1.75] in ambulatory systolic BP and − 2.44 mmHg [95%CI -3.31, -1.57] in ambulatory diastolic BP.ConclusionDespite recent data indicating that RDN might be an effective treatment for patients with resistant hypertension when compared to a sham intervention, our results indicate that the sham intervention for RDN also has a significant effect on lowering Office and Ambulatory (24-h) Blood Pressure in adult patients with hypertension. This highlights that BP itself might be sensitive to placebo-like effect and also brings further difficulties in establishing the BP lowering efficacy of invasive interventions due to the magnitude of the sham effect.

50. Effectiveness of Renal Denervation in Patients with Resistant Hypertension: An Umbrella and Mapping Review

Background: Resistant hypertension is a condition when blood pressure remains high despite the routine consumption of three antihypertensive agents, including diuretics. Due to the unwanted side effects of antihypertensive agents, non-pharmacology therapy such as renal denervation can be chosen as alternative management, even though this modality still remain controversial. This umbrella review appraises published meta-analyses of observational, controlled trial, and randomized controlled trial (RCT) for the efficacy of renal denervation in hypertension. Objective: The aim of this umbrella review is to provide an overview of the efficacy of controversial renal denervation as an alternative management in the case of resistant hypertension. Method: Eight databases were searched was the beginning of 2012 to the 15th of January 2023. Thirteen meta-analyses were included. Non-English languages, wrong study type, wrong population, and wrong study outcomes were excluded. Result: Eight of thirteen meta-analyses showed significant benefits of renal denervation in reducing blood pressure. Furthermore, one of which showed that the efficacy of renal denervation is better than pharmacological therapy in lowering the blood pressure in resistant hypertension. No significant benefit of renal denervation was found in any other meta-analyses, nonetheless, it was safe to use. Conclusion: Despite various results from multiple meta-analyses, this umbrella review reveals that renal denervation is beneficial in lowering the blood pressure in resistant hypertension. Further research using long-term follow-up and big-scale subjects is needed to confirm this result.

Emerging topics on renal denervation in hypertension: anatomical and functional aspects of renal nerves.

Inappropriate sympathetic activation is closely associated with the development and progression of hypertension. Renal denervation (RDN) is a neuromodulation therapy performed using an intraarterial catheter in patients with hypertension. Recent randomized sham-operated controlled trials have shown that RDN has significant antihypertensive effects that last for at least 3 years. Based on this evidence, RDN is nearly ready for general clinical application. On the other hand, there are remaining issues to be addressed, including elucidation of the precise antihypertensive mechanisms of RDN, the appropriate endpoint of RDN during the procedure, and the association between reinnervation after RDN and the long-term effects of RDN. This mini review focuses on studies implicating anatomy of the renal nerves, which consist of afferent or efferent and sympathetic or parasympathetic nerves, the response of blood pressure to renal nerve stimulation, and reinnervation of renal nerves after RDN. A comprehensive understanding of the anatomical and functional aspects of the renal nerves and the antihypertensive mechanisms of RDN, including its long-term effects, will enhance our ability to incorporate RDN into strategies to treat hypertension in clinical practice. This mini review focuses on studies implicating anatomy of the renal nerves, which consist of afferent or efferent and sympathetic or parasympathetic nerves, the response of blood pressure to renal nerve stimulation, and reinnervation of renal nerves after renal denervation. Whether the ablation site is sympathetic dominant or parasympathetic dominant, and afferent dominant or efferent dominant, would in turn determine the final output of renal denervation. BP: blood pressure.

Peregrine system infusion catheter for neurolytic renal denervation in hypertension: an overview of its safety and efficacy

ABSTRACT Introduction Resistant hypertension (HTN), despite the tremendous advances in pharmacotherapy, is a major global problem. Transcatheter renal denervation (RDN) could be a pertinent strategy for resistant HTN and patients with poor pharmacotherapy adherence. Nonetheless, the adoption of energy-based RDN in clinical practice is slow and alternative approaches are needed. Areas covered The review focuses on the assessment of the Peregrine System Infusion Catheters. The system is designed for chemically mediated transcatheter RDN by the infusion publications on the Peregrine system. The theoretical assumptions for chemically mediated RDN, design of the system, data from preclinical and clinical studies, and further perspectives are discussed. Expert opinion Peregrine System Infusion Catheters are the only catheter on the market designed for chemically mediated RDN by the infusion of the neurolytic agent. Chemical neurolysis more efficiently destroys nerves around the renal artery in comparison to energy-based catheters, due to deeper tissue penetration and circumferential distribution resulting in a wider range of effective nerve injury. Chemically mediated RDN by the infusion of the neurolytic agent (alcohol) has an excellent safety profile as confirmed in initial clinical trials which also suggested high efficacy. Currently, there is an ongoing phase III sham–control study. Other possible applications of this technology include clinical settings like heart failure or atrial fibrillation.

Renal Denervation for Hypertension: A Systematic Review and Meta-Analysis of Randomized,Blinded, Placebo-Controlled Trials.

The authors performed an updated meta-analysis of randomized placebo-controlled trials of renal denervation and specifically compared the effect of renal denervation in patients taking medications and in those not taking medications. Renal denervation has now undergone several blinded placebo-controlled trials, covering the spectrum from patients with drug-resistant hypertension to those not yet taking antihypertensive medications. All blinded placebo-controlled randomized trials of catheter-based renal sympathetic denervation for hypertension were systematically identified, and a random-effects meta-analysis was performed. The primary efficacy outcome was the change in ambulatory systolic blood pressure beyond the effect of the placebo procedure. Analysis was stratified by whether there was background antihypertensive medication use. There were 7 eligible trials, totaling 1,368 patients. Denervation significantly reduced ambulatory systolic (mean difference-3.61mmHg; 95% CI:-4.89 to -2.33mmHg; P< 0.0001), ambulatory diastolic (-1.85mmHg; 95%CI:-2.78 to-0.92mmHg; P< 0.0001), office systolic (-5.86mmHg; 95%CI:-7.77 to-3.94mmHg; P< 0.0001), and office diastolic (-3.63mmHg; 95%CI:-4.77 to-2.50; P< 0.0001) blood pressure. There was no evidence that the use of concomitant antihypertensive medication had a significant impact on the effect of denervation on any of these endpoints (Pinteraction=NS for each comparison). The randomized placebo-controlled trials show consistently that renal denervation provides significant reduction in ambulatory and office blood pressure. Although the magnitude of benefit, about 4/2mmHg, is modest, it is similar between patients on background antihypertensive medications and those who are not. Denervation could therefore be a useful strategy at various points for patients who are not willing to add antihypertensive agents. Whether the effect changes with time is currently unknown.

TCT-264 Role of Renal Denervation in Hypertension: An Updated Meta-Analysis of Randomized Sham Controlled Trials

TCT-264 Role of Renal Denervation in Hypertension: An Updated Meta-Analysis of Randomized Sham Controlled Trials

Renal Denervation in Hypertension.

The column in this issue is supplied by Drs. Benjamin Lee, MD, and Usman Ansari, DO. Dr. Lee is an assistant professor of clinical medicine at the Houston Methodist Institute for Academic Medicine and Weill Cornell Medical College. After earning his medical degree at Harvard Medical School, Dr. Lee completed a residency in internal medicine and a nephrology fellowship at the University of California San Francisco (UCSF) while simultaneously obtaining a master of advanced study in clinical research from the UCSF departments of Epidemiology and Biostatistics. He maintains his clinical practice with the Houston Kidney Consultants. Dr. Ansari earned a Doctor of Osteopathy from Touro University College of Osteopathic Medicine in California and is completing his internal medicine residency at Houston Methodist.

α 2-Adrenoceptors: Challenges and Opportunities-Enlightenment from the Kidney.

It was indeed a Don Quixote-like pursuit of the mechanism of essential hypertension when we serendipitously discovered α2-adrenoceptors (α2-ARs) in skin-lightening experiments in the frog. Now α2-ARs lurk on the horizon involving hypertension causality, renal denervation for hypertension, injury from falling in the elderly and prazosin's mechanism of action in anxiety states such as posttraumatic stress disorder (PTSD). Our goal here is to focus on this horizon and bring into clear view the role of α2-AR-mediated mechanisms in these seemingly unrelated conditions. Our narrative begins with an explanation of how experiments in isolated perfused kidneys led to the discovery of a sodium-retaining process, a fundamental mechanism of hypertension, mediated by α2-ARs. In this model system and in the setting of furosemide-induced sodium excretion, α2-AR activation inhibited adenylate cyclase, suppressed cAMP formation, and caused sodium retention. Further investigations led to the realization that renal α2-AR expression in hypertensive animals is elevated, thus supporting a key role for kidney α2-ARs in the pathophysiology of essential hypertension. Subsequent studies clarified the molecular pathways by which α2-ARs activate prohypertensive biochemical systems. While investigating the role of α1-adrenoceptors (α1-ARs) versus α2-ARs in renal sympathetic neurotransmission, we noted an astonishing result: in the kidney α1-ARs suppress the postjunctional expression of α2-ARs. Here, we describe how this finding relates to a broader understanding of the role of α2-ARs in diverse disease states. Because of the capacity for qualitative and quantitative monitoring of α2-AR-induced regulatory mechanisms in the kidney, we looked to the kidney and found enlightenment.

Renal denervation for hypertension: we've come a long way!

Renal sympathetic denervation (RSD), a therapeutic intervention for patients with hypertension (HTN), is undergoing active investigation. Prospective cohort studies and first-generation randomized controlled studies established the safety of RSD but its impact on blood pressure was variable (1-3).

Clinic Versus Ambulatory Blood Pressure in Resistant Hypertension: Impact of Antihypertensive Medication Nonadherence: A Post Hoc Analysis the DENERHTN Study.

Clinic-ambulatory blood pressure (BP) difference is influenced by patients- and device-related factors and inadequate clinic-BP measurement. We investigated whether nonadherence to antihypertensive medications may also influence this difference in a post hoc analysis of the DENERHTN trial (Renal Denervation for Hypertension). We pooled the data of 77 out of 106 evaluable patients with apparent resistant hypertension who received a standardized antihypertensive treatment and had both ambulatory BP and drug-screening results available at baseline after 1 month of standardized triple therapy and at 6 months on a median of 5 antihypertensive drugs. After drug assay samplings on study visits, patients took their antihypertensive treatment under supervision immediately after the start of the ambulatory BP recording, and supine clinic BP was measured 24 hours post-dosing; both allowed to calculate the clinic minus daytime ambulatory systolic BP (SBP) difference (clinic-SBP-day-SBP). A total of 29 (37.7%) were found nonadherent to medications at baseline and 38 (49.4%) at 6 months. At baseline, the mean clinic-SBP-day-SBP difference in the nonadherent group was 12.7 mm Hg (95% CI, 7.8-17.7 mm Hg, P<0.001). In contrast, clinic SBP was almost identical to day-SBP in the adherent group (clinic-SBP-day-SBP difference, 0.1 mm Hg; 95% CI, -3.3 to 3.5 mm Hg; P=0.947). Similar observations were made at 6 months. Using receiver operating characteristics curves, we found that a 6 mm Hg cutoff of clinic-SBP-day-SBP difference had 67% sensitivity and 69% specificity to predict nonadherence to the triple therapy at baseline. In conclusion, a large clinic-SBP-day-SBP difference may help discriminating between adherence and nonadherence to treatment in patients with resistant hypertension. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01570777.

Renal Artery Denervation for Hypertension.

Hypertension (HTN) has a growing impact, already affecting over 1 billion people. An estimated 2-16% of those with HTN have resistant HTN. The sympathetic nervous system (SNS) is a recognized contributor to the pathophysiology of resistant HTN. Current hypertensive pharmacotherapy has not fully targeted the SNS; therefore, the SNS has become a prominent research therapeutic target. This review summarizes the evidence and rationale behind renal denervation (RDN) therapy and the technology available. Prior to the SYMPLICITY HTN-3 clinical trial, trials found RDN to be an effective procedure to control resistant hypertension. The failure of SYMPLICITY HTN-3 to meet its primary efficacy endpoint sparked further studies to address potential shortcomings. The subsequent SPYRAL program trials demonstrated efficacy of RDN therapy in a controlled manner; however, they were not adequately powered. Ongoing research is examining new, innovative RDN technology as well as defining appropriate patients to target for treatment. The data currently available for RDN in HTN and other states of SNS activation suffer from potential biases and limitations, highlighting the need for continued exploration. Contemporary studies are more promising and hypothesis-generating. Future trials and continued device innovation will be crucial for understanding the clinical applications of RDN therapy.

Renal denervation in hypertension: Towards a true revival?

Renal denervation in hypertension: Towards a true revival?

Renewed hopes for renal denervation in hypertension

Renewed hopes for renal denervation in hypertension

Abdominal Aortic Calcifications Influences the Systemic and Renal Hemodynamic Response to Renal Denervation in the DENERHTN (Renal Denervation for Hypertension) Trial.

BackgroundThe DENERHTN (Renal Denervation for Hypertension) trial confirmed the efficacy of renal denervation (RDN) in lowering daytime ambulatory systolic blood pressure when added to standardized stepped‐care antihypertensive treatment (SSAHT) for resistant hypertension at 6 months.Methods and ResultsThis post hoc exploratory analysis assessed the impact of abdominal aortic calcifications (AAC) on the hemodynamic and renal response to RDN at 6 months. In total, 106 patients with resistant hypertension were randomly assigned to RDN plus SSAHT or to the same SSAHT alone (control group). Total AAC volume was measured, with semiautomatic software and blind to randomization, from the aortic hiatus to the iliac bifurcation using the prerandomization noncontrast abdominal computed tomography scans of 90 patients. Measurements were expressed as tertiles. The baseline‐adjusted difference in the change in daytime ambulatory systolic blood pressure from baseline to 6 months between the RDN and control groups was −10.1 mm Hg (P=0.0462) in the lowest tertile and −2.5 mm Hg (P=0.4987) in the 2 highest tertiles of AAC volume. Estimated glomerular filtration rate remained stable at 6 months for the patients in the lowest tertile of AAC volume who underwent RDN (+2.5 mL/min per 1.73 m2) but decreased in the control group (−8.0 mL/min per 1.73 m2, P=0.0148). In the 2 highest tertiles of AAC volume, estimated glomerular filtration rate decreased similarly in the RDN and control groups (P=0.2640).ConclusionsRDN plus SSAHT resulted in a larger decrease in daytime ambulatory systolic blood pressure than SSAHT alone in patients with a lower AAC burden than in those with a higher AAC burden. This larger decrease in daytime ambulatory systolic blood pressure was not associated with a decrease in estimated glomerular filtration rate.Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT01570777.