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Methodist DeBakey Cardiovascular Journal 2015Patients with resistant hypertension are a subgroup of the hypertensive population that are at even greater risk of cardiovascular outcomes. Therapeutic options for... (Review)
Review
Patients with resistant hypertension are a subgroup of the hypertensive population that are at even greater risk of cardiovascular outcomes. Therapeutic options for these patients are limited to antihypertensive medications. However, renal denervation (RDN) is a novel nonpharmacologic intervention that involves a catheter-based ablation of the sympathetic nerves within the renal artery wall. The procedure initially showed promise with remarkable blood pressure reductions until the pivotal SYMPLICITY HTN-3 trial failed to demonstrate superiority of RDN over control. This trial was notable for a substantial placebo effect and an attenuated response to RDN. These findings, which contradicted those of prior studies, have raised numerous questions, including whether adequate RDN occurred in those patients. Further research is planned to resolve some of these questions and to clarify the role of RDN in treating patients with resistant hypertension.
Topics: Antihypertensive Agents; Blood Pressure; Catheter Ablation; Drug Resistance; Humans; Hypertension; Kidney; Randomized Controlled Trials as Topic; Renal Artery; Sympathectomy; Treatment Outcome
PubMed: 27057294
DOI: 10.14797/mdcj-11-4-240 -
Journal of the American Heart... Aug 2023BACKGROUND Renal denervation has proven its efficacy to lower blood pressure in comparison to sham treatment in recent randomized clinical trials. Although there is a...
BACKGROUND Renal denervation has proven its efficacy to lower blood pressure in comparison to sham treatment in recent randomized clinical trials. Although there is a large body of evidence for the durability and safety of radiofrequency-based renal denervation, there are a paucity of data for endovascular ultrasound-based renal denervation (uRDN). We aimed to assess the long-term efficacy and safety of uRDN in a single-center cohort of patients. METHODS AND RESULTS Data from 2 previous studies on uRDN were pooled. Ambulatory 24-hour blood pressure measurements were taken before as well as 3, 6, 12, and 24 months after treatment with uRDN. A total of 130 patients (mean age 63±9 years, 24% women) underwent uRDN. After 3, 6, 12, and 24 months, systolic mean 24-hour ambulatory blood pressure values were reduced by 10±12, 10±14, 8±15, and 10±15 mm Hg, respectively, when compared with baseline (<0.001). Corresponding diastolic values were reduced by 6±8, 6±8, 5±9, and 6±9 mm Hg, respectively (<0.001). Periprocedural adverse events occurred in 16 patients, and all recovered without sequelae. CONCLUSIONS In this single-center study, uRDN effectively lowered blood pressure up to 24 months after treatment.
Topics: Humans; Female; Middle Aged; Aged; Male; Hypertension; Blood Pressure; Antihypertensive Agents; Blood Pressure Monitoring, Ambulatory; Renal Artery; Treatment Outcome; Kidney; Sympathectomy; Denervation
PubMed: 37581398
DOI: 10.1161/JAHA.123.030767 -
Anatomical Record (Hoboken, N.J. : 2007) Aug 2019Insufficient recovery after injury of a peripheral motor nerve is due to (1) inappropriate pathfinding as a result of axonal regrowth to inappropriate targets, (2)... (Review)
Review
Insufficient recovery after injury of a peripheral motor nerve is due to (1) inappropriate pathfinding as a result of axonal regrowth to inappropriate targets, (2) excessive collateral axonal branching at the lesion site, and (3) polyinnervation of the neuromuscular junctions (NMJs). The rat facial nerve model is often used because of its simple and reliable readout to measure recovery of function (vibrissal whisking). Over the last decades scientists have concentrated their efforts to combat mostly NMJ polyinnervation, because it turned out to be very difficult to reduce collateral axonal branching and impossible to navigate thousands of axons toward the original fascicles. In the past, several groups of scientists concentrated their efforts to reduce the activity-dependent polyinnervation of NMJs by electrical stimulation of the muscles (square 0.1 msec pulses at 5 Hz). The results showed no recovery of functions and a severe reduction in the number of innervated NMJs to approximately one fifth of those observed in intact animals. More recent experiments, however, have shown that motor recovery improved significantly following mechanical stimulation of the denervated facial muscles (vibrissal and orbicularis oculi) and that restored functions could invariably be linked to reduced polyinnervation at the NMJ while the number of innervated NMJ remained the same. These results suggest that clinically feasible and effective therapies could be developed and tested in the near future. Anat Rec, 302:1287-1303, 2019. © 2019 Wiley Periodicals, Inc.
Topics: Animals; Disease Models, Animal; Facial Muscles; Facial Nerve; Facial Nerve Injuries; Humans; Muscle Denervation; Nerve Regeneration; Rats; Recovery of Function; Vibrissae
PubMed: 30950181
DOI: 10.1002/ar.24123 -
The Cochrane Database of Systematic... Feb 2017Resistant hypertension is highly prevalent among the general hypertensive population and the clinical management of this condition remains problematic. Different... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Resistant hypertension is highly prevalent among the general hypertensive population and the clinical management of this condition remains problematic. Different approaches, including a more intensified antihypertensive therapy, lifestyle modifications, or both, have largely failed to improve patients' outcomes and to reduce cardiovascular and renal risk. As renal sympathetic hyperactivity is a major driver of resistant hypertension, renal sympathetic ablation (renal denervation) has been recently proposed as a possible therapeutic alternative to treat this condition.
OBJECTIVES
We sought to evaluate the short- and long-term effects of renal denervation in individuals with resistant hypertension on clinical end points, including fatal and non-fatal cardiovascular events, all-cause mortality, hospital admissions, quality of life, blood pressure control, left ventricular hypertrophy, cardiovascular and metabolic profile, and kidney function, as well as the potential adverse events related to the procedure.
SEARCH METHODS
We searched the following databases to 17 February 2016 using relevant search terms: the Cochrane Hypertension Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and ClinicalTrials.gov SELECTION CRITERIA: We considered randomised controlled trials (RCTs) that compared renal denervation to standard therapy or sham procedure to treat resistant hypertension, without language restriction.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and assessed study risks of bias. We summarised treatment effects on available clinical outcomes and adverse events using random-effects meta-analyses. We assessed heterogeneity in estimated treatment effects using Chi² and I² statistics. We calculated summary treatment estimates as a mean difference (MD) or standardised mean difference (SMD) for continuous outcomes, and a risk ratio (RR) for dichotomous outcomes, together with their 95% confidence intervals (CI).
MAIN RESULTS
We found 12 eligible studies (1149 participants). In four studies, renal denervation was compared to sham procedure; one study compared a proximal ablation to a complete renal artery denervation; in the remaining, renal denervation was tested against standard or intensified antihypertensive therapy.None of the included trials was designed to look at hard clinical end points as primary outcomes.When compared to control, there was low quality evidence that renal denervation did not reduce the risk of myocardial infarction (4 studies, 742 participants; RR 1.31, 95% CI 0.45 to 3.84), ischaemic stroke (4 studies, 823 participants; RR 1.15, 95% CI 0.36 to 3.72), or unstable angina (2 studies, 201 participants; RR 0.63, 95% CI 0.08 to 5.06), and moderate quality evidence that it had no effect on 24-hour ambulatory blood pressure monitoring (ABPM) systolic BP (5 studies, 797 participants; MD 0.28 mmHg, 95% CI -3.74 to 4.29), diastolic BP (4 studies, 756 participants; MD 0.93 mmHg, 95% CI -4.50 to 6.36), office measured systolic BP (6 studies, 886 participants; MD -4.08 mmHg, 95% CI -15.26 to 7.11), or diastolic BP (5 studies, 845 participants; MD -1.30 mmHg, 95% CI -7.30 to 4.69). Furthermore, low quality evidence suggested that this procedure produced no effect on either serum creatinine (3 studies, 736 participants, MD 0.01 mg/dL; 95% CI -0.12 to 0.14), estimated glomerular filtration rate (eGFR), or creatinine clearance (4 studies, 837 participants; MD -2.09 mL/min, 95% CI -8.12 to 3.95). Based on low-quality evidence, renal denervation significantly increased bradycardia episodes compared to control (3 studies, 220 participants; RR 6.63, 95% CI 1.19 to 36.84), while the risk of other adverse events was comparable or not assessable.Data were sparse or absent for all cause mortality, hospitalisation, fatal cardiovascular events, quality of life, atrial fibrillation episodes, left ventricular hypertrophy, sleep apnoea severity, need for renal replacement therapy, and metabolic profile.The quality of the evidence was low for cardiovascular outcomes and adverse events and moderate for lack of effect on blood pressure and renal function.
AUTHORS' CONCLUSIONS
In patients with resistant hypertension, there is low quality evidence that renal denervation does not change major cardiovascular events, and renal function. There was moderate quality evidence that it does not change blood pressure and and low quality evidence that it caused an increaseof bradycardia episodes. Future trials measuring patient-centred instead of surrogate outcomes, with longer follow-up periods, larger sample size and more standardized procedural methods are necessary to clarify the utility of this procedure in this population.
Topics: Angina, Unstable; Antihypertensive Agents; Blood Pressure Determination; Drug Resistance; Humans; Hypertension; Kidney; Myocardial Infarction; Stroke; Sympathectomy
PubMed: 28220472
DOI: 10.1002/14651858.CD011499.pub2 -
The Netherlands Journal of Medicine Nov 2014
Topics: Coronary Vasospasm; Denervation; Humans; Hypertension; Kidney; Practice Guidelines as Topic
PubMed: 25431388
DOI: No ID Found -
Renal denervation in patients with chronic kidney disease: current evidence and future perspectives.Nephrology, Dialysis, Transplantation :... May 2023Supported by several high-quality randomized controlled trials and registry analyses, catheter-based renal denervation is becoming an important adjunctive treatment... (Review)
Review
Supported by several high-quality randomized controlled trials and registry analyses, catheter-based renal denervation is becoming an important adjunctive treatment modality for the safe and efficacious treatment of hypertension besides lifestyle modifications and antihypertensive medication. Renal denervation is of particular interest to nephrologists as the intervention may provide additional benefits to hypertensive people with chronic kidney disease (CKD), a condition typically characterized by sympathetic hyperactivity. A growing body of clinical evidence supports the safety and efficacy of renal denervation in this difficult-to-control population. In addition, preclinical and clinical research works indicate potential nephroprotective effects in CKD patients. The current review examines recent research on renal denervation with a focus on renal disease and assesses the latest findings and their implications from a nephrologist's perspective.
Topics: Humans; Kidney; Renal Insufficiency, Chronic; Hypertension; Antihypertensive Agents; Treatment Outcome; Denervation; Sympathectomy; Blood Pressure
PubMed: 35617138
DOI: 10.1093/ndt/gfac189 -
Current Neuropharmacology 2016Vagotomy reduces gastric acid secretion and was therefore introduced as a surgical treatment for peptic ulcers in the 1970s. Later, it was replaced by acid reducing... (Review)
Review
Vagotomy reduces gastric acid secretion and was therefore introduced as a surgical treatment for peptic ulcers in the 1970s. Later, it was replaced by acid reducing medication, such as histamine type 2 (H2) receptor antagonists and proton pump inhibitors (PPIs). A large body of evidence has indicated that drug-induced hypochlorhydria per se does not increase the risk of gastric cancer. Early studies on the effects of vagotomy in chemically-induced rodent models of gastric cancer reported an increased risk of developing gastric cancer. This was most likely due to a delayed gastric emptying, which later has been accounted for by including an additional drainage procedure, e.g. pyloroplasty. In a recent study using three different mouse models of gastric cancer (including genetically engineered, chemically-induced and Helicobacter pylori-infected mice), either unilateral vagotomy or bilateral truncal vagotomy with pyloroplasty was found to significantly attenuate tumorigenesis in the denervated side of the stomach at early preneoplastic stages as well as at later stages of tumorigenesis. Consistently, pharmacological denervation using botulinum toxin A or muscarinic acetylcholine receptor 3 (M3R) blockade inhibited tumorigenesis. Moreover, it was found that recurrence of gastric cancer was reduced in patients following vagotomy. Thus, these new findings suggest the potential treatment strategies to target the nerve, neurotransmitters, corresponding receptors and their downstream signaling pathways for the malignancy.
Topics: Animals; Carcinogenesis; Humans; Stomach Neoplasms; Vagotomy
PubMed: 26791481
DOI: 10.2174/1570159x14666160121114854 -
Cardiovascular Therapeutics Jun 2015Catheter-based renal denervation (RDN) is a novel invasive approach in the treatment of resistant hypertension. It is considered a minimally invasive and safe procedure...
Catheter-based renal denervation (RDN) is a novel invasive approach in the treatment of resistant hypertension. It is considered a minimally invasive and safe procedure which, as shown by initial experimental and clinical trials, is able not only to reduce blood pressure but also to modify its risk factors by modulation of autonomic nervous system. Recently published results of a randomized Symplicity HTN-3 trial, which failed to demonstrate RDN-induced reduction of blood pressure at six months, decreased the initial enthusiasm regarding RDN and raised a question about real efficacy of this procedure. Nevertheless, still there are some other conditions characterized by increased sympathetic tone such as heart failure, atrial fibrillation, or ventricular arrhythmias that may benefit from RDN. Furthermore, novel therapeutical approach toward RDN using adapted electrophysiological or new specially designed electrodes may improve effectiveness of RDN procedure.
Topics: Blood Pressure; Catheter Ablation; Denervation; Humans; Hypertension; Kidney
PubMed: 25786785
DOI: 10.1111/1755-5922.12116 -
Biochemical Pharmacology Sep 2022The molecular mechanism underlying denervation-induced muscle atrophy is complex and incompletely understood. Our previous results suggested that inflammation may play...
The molecular mechanism underlying denervation-induced muscle atrophy is complex and incompletely understood. Our previous results suggested that inflammation may play an important role in the early stages of muscle atrophy. Celecoxib is reported to exert anti-inflammatory effects. Here, we explored the effect of celecoxib on denervation-induced muscle atrophy and sought to identify the mechanism involved. We found that celecoxib treatment significantly increased the wet weight ratio and CSA of the tibialisanteriormuscle. Additionally, celecoxib downregulated the levels of COX-2, inflammatory factors and reduced inflammatory cell infiltration. GO and KEGG pathway enrichment analysis indicated that after 3 days of celecoxib treatment in vivo, the differentially expressed genes (DEGs) were mainly associated with the regulation of immune responses related to complement activation; after 14 days, the DEGs were mainly involved in the regulation of oxidative stress and inflammation-related responses. Celecoxib administration reduced the levels of ROS and oxidative stress-related proteins. Furthermore, we found that celecoxib treatment inhibited the denervation-induced up-regulation of the ubiquitin-proteasome and autophagy-lysosomal systems related proteins; decreased mitophagy in target muscles; and increased levels of MHC. Finally, celecoxib also attenuated microvascular damage in denervated skeletal muscle. Combined, our findings demonstrated that celecoxib inhibits inflammation and oxidative stress in denervated skeletal muscle, thereby suppressing mitophagy and proteolysis, improving blood flow in target muscles, and, ultimately, alleviating denervation-induced muscle atrophy. Our results confirmed that inflammatory responses play a key role in denervation-induced muscle atrophy and highlight a novel strategy for the prevention and treatment of this condition.
Topics: Celecoxib; Humans; Inflammation; Microcirculation; Muscle Denervation; Muscle, Skeletal; Muscular Atrophy; Oxidative Stress
PubMed: 35882305
DOI: 10.1016/j.bcp.2022.115186 -
American Journal of Physiology. Renal... Oct 2015When introduced clinically 6 years ago, renal denervation was thought to be the solution for all patients whose blood pressure could not be controlled by medication. The... (Review)
Review
When introduced clinically 6 years ago, renal denervation was thought to be the solution for all patients whose blood pressure could not be controlled by medication. The initial two studies, SYMPLICITY HTN-1 and HTN-2, demonstrated great magnitudes of blood pressure reduction within 6 mo of the procedure and were based on a number of assumptions that may not have been true, including strict adherence to medication and absence of white-coat hypertension. The SYMPLICITY HTN-3 trial controlled for all possible factors believed to influence the outcome, including the addition of a sham arm, and ultimately proved the demise of the initial overly optimistic expectations. This trial yielded a much lower blood pressure reduction compared with the previous SYMPLICITY trials. Since its publication in 2014, there have been many analyses to try and understand what accounted for the differences. Of all the variables examined that could influence blood pressure outcomes, the extent of the denervation procedure was determined to be inadequate. Beyond this, the physiological mechanisms that account for the heterogeneous fall in arterial pressure following renal denervation remain unclear, and experimental studies indicate dependence on more than simply reduced renal sympathetic activity. These and other related issues are discussed in this paper. Our perspective is that renal denervation works if done properly and used in the appropriate patient population. New studies with new approaches and catheters and appropriate controls will be starting later this year to reassess the efficacy and safety of renal denervation in humans.
Topics: Denervation; Drug Resistance; Humans; Hypertension, Renal; Kidney; Renal Circulation; Sympathectomy
PubMed: 26224718
DOI: 10.1152/ajprenal.00246.2015