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Journal of the American College of... Nov 2022
Topics: Humans; Kidney; Sympathectomy; Hypertension; Denervation; Blood Pressure; Antihypertensive Agents
PubMed: 36357088
DOI: 10.1016/j.jacc.2022.09.025 -
Annual Review of Physiology Feb 2021Heart failure (HF) is a global pandemic with a poor prognosis after hospitalization. Despite HF syndrome complexities, evidence of significant sympathetic overactivity... (Review)
Review
Heart failure (HF) is a global pandemic with a poor prognosis after hospitalization. Despite HF syndrome complexities, evidence of significant sympathetic overactivity in the manifestation and progression of HF is universally accepted. Confirmation of this dogma is observed in guideline-directed use of neurohormonal pharmacotherapies as a standard of care in HF. Despite reductions in morbidity and mortality, a growing patient population is resistant to these medications, while off-target side effects lead to dismal patient adherence to lifelong drug regimens. Novel therapeutic strategies, devoid of these limitations, are necessary to attenuate the progression of HF pathophysiology while continuing to reduce morbidity and mortality. Renal denervation is an endovascular procedure, whereby the ablation of renal nerves results in reduced renal afferent and efferent sympathetic nerve activity in the kidney and globally. In this review, we discuss the current state of preclinical and clinical research related to renal sympathetic denervation to treat HF.
Topics: Animals; Disease Progression; Heart Failure; Humans; Kidney; Sympathectomy
PubMed: 33074771
DOI: 10.1146/annurev-physiol-031620-093431 -
Hypertension Research : Official... Feb 2022
Topics: Denervation; Kidney
PubMed: 34912048
DOI: 10.1038/s41440-021-00808-w -
The Cochrane Database of Systematic... Nov 2021Resistant hypertension is highly prevalent among the general hypertensive population and the clinical management of this condition remains problematic. Different... (Review)
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, in the last decade renal sympathetic ablation (renal denervation) has been 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
For this updated review, the Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to 3 November 2020: Cochrane Hypertension's Specialised Register, CENTRAL (2020, Issue 11), Ovid MEDLINE, and Ovid Embase. The World Health Organization International Clinical Trials Registry Platform (via CENTRAL) and the US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov were searched for ongoing trials. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions.
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 risk 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). Certainty of evidence has been assessed using the GRADE approach.
MAIN RESULTS
We found 15 eligible studies (1416 participants). In four studies, renal denervation was compared to sham procedure; in the remaining studies, renal denervation was tested against standard or intensified antihypertensive therapy. Most studies had unclear or high risk of bias for allocation concealment and blinding. When compared to control, there was low-certainty evidence that renal denervation had little or no effect on the risk of myocardial infarction (4 studies, 742 participants; RR 1.31, 95% CI 0.45 to 3.84), ischaemic stroke (5 studies, 892 participants; RR 0.98, 95% CI 0.33 to 2.95), unstable angina (3 studies, 270 participants; RR 0.51, 95% CI 0.09 to 2.89) or hospitalisation (3 studies, 743 participants; RR 1.24, 95% CI 0.50 to 3.11). Based on moderate-certainty evidence, renal denervation may reduce 24-hour ambulatory blood pressure monitoring (ABPM) systolic BP (9 studies, 1045 participants; MD -5.29 mmHg, 95% CI -10.46 to -0.13), ABPM diastolic BP (8 studies, 1004 participants; MD -3.75 mmHg, 95% CI -7.10 to -0.39) and office diastolic BP (8 studies, 1049 participants; MD -4.61 mmHg, 95% CI -8.23 to -0.99). Conversely, this procedure had little or no effect on office systolic BP (10 studies, 1090 participants; MD -5.92 mmHg, 95% CI -12.94 to 1.10). Moderate-certainty evidence suggested that renal denervation may not reduce serum creatinine (5 studies, 721 participants, MD 0.03 mg/dL, 95% CI -0.06 to 0.13) and may not increase the estimated glomerular filtration rate (eGFR) or creatinine clearance (6 studies, 822 participants; MD -2.56 mL/min, 95% CI -7.53 to 2.42). AUTHORS' CONCLUSIONS: In patients with resistant hypertension, there is low-certainty evidence that renal denervation does not improve major cardiovascular outomes and renal function. Conversely, moderate-certainty evidence exists that it may improve 24h ABPM and diastolic office-measured BP. Future trials measuring patient-centred instead of surrogate outcomes, with longer follow-up periods, larger sample size and more standardised procedural methods are necessary to clarify the utility of this procedure in this population.
Topics: Antihypertensive Agents; Blood Pressure; Denervation; Humans; Hypertension; Kidney
PubMed: 34806762
DOI: 10.1002/14651858.CD011499.pub3 -
Cardiology Journal 2022Pulmonary arterial hypertension (PAH) is a chronic pulmonary vascular disease characterized by increased pulmonary arterial pressure and pulmonary arterioles remodeling.... (Review)
Review
Pulmonary arterial hypertension (PAH) is a chronic pulmonary vascular disease characterized by increased pulmonary arterial pressure and pulmonary arterioles remodeling. Some studies have discovered the relationship between sympathetic nerves (SNs) and pathogenesis of PAH. This review is aimed to illustrate the location and components of SNs in the pulmonary artery, along with different methods and effects of pulmonary artery denervation (PADN). Studies have shown that the SNs distributed mainly around the main pulmonary artery and pulmonary artery bifurcation. And the SNs could be destroyed by three ways: the chemical way, the surgical way and the catheter-based way. PADN can significantly decrease pulmonary arterial pressure rapidly, improve hemodynamic varieties, and then palliate PAH. PADN has been recognized as a prospective and effective therapy for PAH patients, especially for those with medication-refractory PAH. However, further enlarged clinical studies are needed to confirm accurate distribution of SNs in the pulmonary artery and the efficacy of PADN.
Topics: Humans; Hypertension, Pulmonary; Prospective Studies; Pulmonary Arterial Hypertension; Pulmonary Artery; Sympathectomy
PubMed: 33438182
DOI: 10.5603/CJ.a2020.0186 -
CMAJ : Canadian Medical Association... Feb 2024
Topics: Humans; Hypertension; Kidney; Denervation
PubMed: 38316459
DOI: 10.1503/cmaj.230745-f -
Journal of Clinical Hypertension... Apr 2020Despite the availability of a numerous antihypertensive agents, hypertension treatment and control rates remain low in many countries. The role of the sympathetic... (Meta-Analysis)
Meta-Analysis Review
Efficacy and safety of renal denervation for the management of arterial hypertension: A systematic review and meta-analysis of randomized, sham-controlled, catheter-based trials.
Despite the availability of a numerous antihypertensive agents, hypertension treatment and control rates remain low in many countries. The role of the sympathetic nervous system has long been recognized, but recent sham control renal denervation studies demonstrated conflicting results. In this reviewe paper, the authors performed a systematic review and meta-analysis to examine outcomes of sham-controlled studies utilizing new technologies and procedures. Six published randomized, sham-controlled studies were included in this meta-analysis. Of those, three trials used the first-generation radiofrequency renal denervation device and technique and the other three used second-generation devices and techniques. In total, 981 patients with hypertension were randomized in all 6 trials to undergo renal denervation (n = 585) or sham procedure (n = 396). Overall, renal denervation resulted in a decrease of 24-hours systolic ambulatory blood pressure (ABP) by 3.62 mm Hg (95% CI: -5.28--1.96; I = 0%), compared to sham procedure (GRADE: low). Renal denervation also reduced daytime systolic ABP by 5.51 mm Hg (95% CI: -7.79--3.23; I = 0%), compared to sham procedure but not nighttime systolic ABP. Office systolic blood pressure was reduced by 5.47 mm Hg (95% CI -8.10--2.84; I = 0%), compared to sham control. Further analysis demonstrated that second-generation devices were effective in reducing blood pressure, whereas the first-generation devices were not. These results indicate that effective renal denervation can result in significant and clinically meaningful blood pressure reduction. The second-generation devices provide better renal nerve ablation.
Topics: Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Catheter Ablation; Catheters; Denervation; Humans; Hypertension; Kidney; Randomized Controlled Trials as Topic; Sympathectomy; Treatment Outcome
PubMed: 32049436
DOI: 10.1111/jch.13827 -
Redox Biology Nov 2022Loss of innervation is a key driver of age associated muscle atrophy and weakness (sarcopenia). Our laboratory has previously shown that denervation induced atrophy is...
Loss of innervation is a key driver of age associated muscle atrophy and weakness (sarcopenia). Our laboratory has previously shown that denervation induced atrophy is associated with the generation of mitochondrial hydroperoxides and lipid mediators produced downstream of cPLA and 12/15 lipoxygenase (12/15-LOX). To define the pathological impact of lipid hydroperoxides generated in denervation-induced atrophy in vivo, we treated mice with liproxstatin-1, a lipid hydroperoxide scavenger. We treated adult male mice with 5 mg/kg liproxstain-1 or vehicle one day prior to sciatic nerve transection and daily for 7 days post-denervation before tissue analysis. Liproxstatin-1 treatment protected gastrocnemius mass and fiber cross sectional area (∼40% less atrophy post-denervation in treated versus untreated mice). Mitochondrial hydroperoxide generation was reduced 80% in vitro and by over 65% in vivo by liproxstatin-1 treatment in denervated permeabilized muscle fibers and decreased the content of 4-HNE by ∼25% post-denervation. Lipidomic analysis revealed detectable levels of 25 oxylipins in denervated gastrocnemius muscle and significantly increased levels for eight oxylipins that are generated by metabolism of fatty acids through 12/15-LOX. Liproxstatin-1 treatment reduced the level of three of the eight denervation-induced oxylipins, specifically 15-HEPE, 13-HOTrE and 17-HDOHE. Denervation elevated protein degradation rates in muscle and treatment with liproxstatin-1 reduced rates of protein breakdown in denervated muscle. In contrast, protein synthesis rates were unchanged by denervation. Targeted proteomics revealed a number of proteins with altered expression after denervation but no effect of liproxstain-1. Transcriptomic analysis revealed 203 differentially expressed genes in denervated muscle from vehicle or liproxstatin-1 treated mice, including ER stress, nitric oxide signaling, Gαi signaling, glucocorticoid receptor signaling, and other pathways. Overall, these data suggest lipid hydroperoxides and oxylipins are key drivers of increased protein breakdown and muscle loss associated with denervation induced atrophy and a potential target for sarcopenia intervention.
Topics: Male; Mice; Animals; Lipid Peroxides; Oxylipins; Sarcopenia; Muscular Atrophy; Muscle, Skeletal; Protein Biosynthesis; Denervation
PubMed: 36283174
DOI: 10.1016/j.redox.2022.102518 -
Hellenic Journal of Cardiology : HJC =... 2020Currently, renal denervation (RDN) has proven its overall procedural and renal safety in registries and trials. Available data, suggest that vascular complications are...
Currently, renal denervation (RDN) has proven its overall procedural and renal safety in registries and trials. Available data, suggest that vascular complications are rather scarce in modern studies using established neuromodulation catheters of different technologies and kidney parameters are mainly maintained stable overtime in RDN patients. Identification of the impact of energy delivery at vascular level by means of advanced methodologies such as optical coherence tomography (OCT) is a meaningful research tool. This accumulation of evidence on the acute and late effects of the procedure in the renal artery tissue especially when a new catheter is tested, as in the present work can further enhance our knowledge on the pathophysiology and clinical outcome of RDN.
Topics: Blood Pressure; Catheter Ablation; Denervation; Humans; Hypertension; Kidney; Renal Artery; Sympathectomy; Treatment Outcome
PubMed: 32916295
DOI: 10.1016/j.hjc.2020.09.002 -
Hypertension Research : Official... Nov 2021Excessive activation of the sympathetic nervous system is one of the pathophysiological hallmarks of hypertension and heart failure. Within the central nervous system,... (Review)
Review
Excessive activation of the sympathetic nervous system is one of the pathophysiological hallmarks of hypertension and heart failure. Within the central nervous system, the paraventricular nucleus (PVN) of the hypothalamus and the rostral ventrolateral medulla in the brain stem play critical roles in the regulation of sympathetic outflow to peripheral organs. Information from the peripheral circulation, including serum concentrations of sodium and angiotensin II, is conveyed to the PVN via adjacent structures with a weak blood-brain barrier. In addition, signals from baroreceptors, chemoreceptors and cardiopulmonary receptors as well as afferent input via the renal nerves are all integrated at the level of the PVN. The brain renin-angiotensin system and the balance between nitric oxide and reactive oxygen species in these brain areas also determine the final sympathetic outflow. Additionally, brain inflammatory responses have been shown to modulate these processes. Renal denervation interrupts both the afferent inputs from the kidney to the PVN and the efferent outputs from the PVN to the kidney, resulting in the suppression of sympathetic outflow and eliciting beneficial effects on both hypertension and heart failure.
Topics: Animals; Blood Pressure; Denervation; Kidney; Paraventricular Hypothalamic Nucleus; Rats; Rats, Sprague-Dawley; Sympathetic Nervous System
PubMed: 34518650
DOI: 10.1038/s41440-021-00746-7