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Renal Sympathetic Denervation - A Review of Applications in Current Practice.

ABSTRACT: Resistant hypertension is associated with high morbidity and mortality despite numerous pharmacological strategies. A wealth of preclinical and clinical data have demonstrated that resistant hypertension is associated with elevated renal and central sympathetic tone. The development of interventional therapies to modulate the sympathetic nervous system potentially represents a paradigm shift in the strategy for blood pressure control in this subset of patients. Initial first-in-man and pivotal, randomised controlled trials of endovascular, radio-frequency renal sympathetic denervation have spawned numerous iterations of similar technology, as well as many novel concepts for achieving effective renal sympatholysis. This review details the current knowledge of these devices and the evidence base behind each technology.

SUBMITTER: Kapil V

PROVIDER: S-EPMC5808654 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Renal Sympathetic Denervation - A Review of Applications in Current Practice.

Kapil Vikas V Jain Ajay K AK Lobo Melvin D MD

Interventional cardiology (London, England) 20140301 1

Resistant hypertension is associated with high morbidity and mortality despite numerous pharmacological strategies. A wealth of preclinical and clinical data have demonstrated that resistant hypertension is associated with elevated renal and central sympathetic tone. The development of interventional therapies to modulate the sympathetic nervous system potentially represents a paradigm shift in the strategy for blood pressure control in this subset of patients. Initial first-in-man and pivotal, ...[more]

PMID: 29588780

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Renal sympathetic denervation for blood pressure control: a review of the current evidence and ongoing studies.

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Reconsidering Renal Sympathetic Denervation for Heart Failure.

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Renal sympathetic denervation in patients with vasospastic angina.

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| S-EPMC7749092 | biostudies-literature

Renal artery sympathetic denervation: observations from the UK experience.

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The Role of Renal Sympathetic Denervation in Atrial Fibrillation.

Project description:Endocardial catheter ablation is a widely used alternative for the treatment of atrial fibrillation (AF). Despite technical improvements, and increased understanding of mechanism, and acquired technical experience over many years, the results are not yet optimal. This results in an ongoing search for new therapeutic approaches. Because cardiac sympathetic drive is potentially responsible for triggering and sustaining AF, modulation of sympathetic tone has been proposed as a viable treatment objective. The early attempts to test this concept were limited by nature=highly intrusive techniques but new approaches and targets have been recently introduced. Specifically, renal nerve ablation has been introduced and the first attempts to employ this technique for treatment of cardiac arrhythmias give as a promise of new therapeutic avenues in near future. This review focuses on the possible role of renal denervation in treatment of atrial fibrillation, the contemporary evidence supporting this approach, and the ongoing trials to establish its therapeutic role.

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Renal denervation - current evidence and perspectives.

Project description:Clinical trials have demonstrated that catheter-based renal denervation (RDN) reduces blood pressure and improves blood pressure control in patients with resistant hypertension. The follow-up data indicate that the blood pressure lowering effect of the procedure may last for up to 36 months. Despite the fact that RDN is a growing and promising technique, still more data from clinical trials are needed to support the long-term safety and persistent efficacy of this approach as compared to the best possible pharmacological treatment. It would also be particularly important to recognize the clinical features of patients who would benefit most from RDN as well as the clinical characteristics of non-responders to the procedure. As renal denervation also reduces whole-body sympathetic nerve activity, the clinical entities characterized by sympathetic nervous system activation - including hypertension coexisting with metabolic abnormalities and/or sleep apnea, chronic kidney disease, heart failure, and arrhythmias - may be potential new indications for the procedure. However, only a few small clinical studies so far have shown the potential benefit of renal denervation in these clinical situations and large clinical trials are needed to prove this concept. Catheter-based RDN is a promising (but also novel) therapeutic approach and further studies should also verify whether it can be considered as a procedure in management of patients not only with resistant hypertension, but also as a tool in the treatment of mild to moderate forms of hypertension.

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Effect of renal sympathetic denervation on ventricular and neural remodeling.

Project description:BACKGROUND:This study assessed the therapeutic effects of renal sympathetic denervation (RDN) on post-myocardial infarction (MI) ventricular remodeling and sympathetic neural remodeling in dogs. The possible mechanisms and optimal time for treatment are discussed. METHODS:We randomly assigned 30 dogs to five groups: RDN 1 week before MI (RDN1w?+?MI; n?=?6), RDN 1 week after MI (MI1w?+?RDN; n?=?6), RDN 2 weeks after MI (MI2w?+?RDN; n?=?6), control (N; n?=?6), and MI (n?=?6). A canine model of myocardial infarction was established by interventional occlusion with a gelatin sponge via the femoral artery. Brain natriuretic peptide (BNP) and endothelin-1 (ET-1) levels were measured and echocardiography was performed to assess cardiac function and heart size. All dogs were killed at the end of the experiment and samples of cardiac and renal arteries were obtained. The expression of matrix metalloproteinase (MMP)-2 and MMP-9 in cardiac and of tyrosine hydroxylase (TH) in renal arteries was assessed by immunohistochemistry. Sympathetic innervations in the infarction border zone were investigated via Western blotting and real-time PCR. RESULTS:Left ventricular function in the MI group decreased significantly, while plasma BNP and ET-1 levels as well as MMP-2 and MMP-9 expression increased. Compared with the MI group, the RD groups showed significantly reduced MMP?2, MMP?9, TH, and growth-associated protein (GAP) 43 expression in the RDN1w?+?MI, MI1w?+?RDN, and MI2w?+?RDN groups was significantly improved. Additionally, the expression of TH in renal arteries decreased after RDN. CONCLUSION:RDN has preventive and therapeutic effects on post-MI ventricular remodeling and sympathetic neural remodeling. The mechanism of RDN is likely mediated through restraint of renal sympathetic nerve activity.

| S-EPMC6890580 | biostudies-literature

Long-term follow-up of patients undergoing renal sympathetic denervation.

Project description:ObjectivesRenal denervation (RDN) proved to significantly lower blood pressure (BP) at 2-6 months in patients on and off antihypertensive drugs. Given a lack of longer-term follow-up data, our aim was to assess the safety and efficacy of RDN up to five years taking into account antihypertensive drug regimen changes over time.MethodsIn the present single-center study, patients underwent RDN for (therapy resistant) hypertension. Patients underwent protocolized yearly follow-up out to five years. Data were collected on 24-h ambulatory BP and office BP monitoring, renal function, antihypertensive drug regimen, and safety events, including non-invasive renal artery imaging at 6/12 months. Efficacy analyses were performed using linear mixed-effects models.ResultsSeventy-two patients with mean age 63.3 ± 9.5 (SD) years (51% female) were included. Median follow-up time was 3.5 years and Clark's Completeness Index was 72%. Baseline ambulatory daytime BP was 146.1/83.7 ± 17.4/12.2 mmHg under a mean number of 4.9 ± 2.7 defined daily doses (DDD). At five years, ambulatory daytime systolic BP as calculated from the mixed model was 120.8 (95% CI 114.2-127.5) mmHg and diastolic BP was 73.3 (95% CI 69.4-77.3) mmHg, implying a reduction of -20.9/-8.3 mmHg as compared to baseline estimates (p < 0.0001). The number of DDDs remained stable over time (p = 0.87). No procedure-related major adverse events resulting in long-term consequences were observed.ConclusionsThe BP-lowering effect of RDN was safely maintained at least five years post-procedure as reflected by a significant decrease in ambulatory daytime BP in the absence of escalating antihypertensive drug therapy over time.

| S-EPMC9622524 | biostudies-literature

Quantification of Renal Sympathetic Vasomotion as a Novel End Point for Renal Denervation.

Project description:Renal sympathetic denervation, a potentially revolutionary interventional treatment for hypertension, faces an existential problem due to the inability to confirm successful ablation of the targeted renal sympathetic nerves. Based on the observation that renal sympathetic nerve activity exerts rhythmic, baroreflex-driven, and vasoconstrictive control of the renal vasculature, we developed a novel technique for identifying rhythmic sympathetic vascular control using a time-varying, 2-component Windkessel model of the renal circulation. This technology was tested in 2 different animal models of renal denervation; 10 rabbits underwent chronic, surgical renal denervation, and 9 pigs underwent acute, functional renal denervation via intrathecal administration of ropivacaine. Both methods of renal denervation reduced negative admittance gain, negative phase shift renal vascular control at known sympathetic vasomotor frequencies, consistent with a reduction in vasoconstrictive, baroreflex-driven renal sympathetic vasomotion. Classic measures like mean renal blood flow and mean renal vascular resistance were not significantly affected in either model of renal denervation. Renal sympathetic vasomotion monitoring could provide intraprocedural feedback for interventionists performing renal denervation and serve more broadly as a platform technology for the evaluation and treatment of diseases affecting the sympathetic nervous system.

| S-EPMC7673653 | biostudies-literature

Evidence of Reduced Efferent Renal Sympathetic Innervation After Chemical Renal Denervation in Humans.

Project description:BackgroundRenal denervation (RDN) is effective at lowering blood pressure. However, it is unknown if ablative procedures elicit sympathetic denervation of the kidneys in humans. The aim of this investigation was to assess sympathetic innervation of the renal cortex following perivascular chemical RDN, which may be particularly effective at ablating perivascular efferent and afferent nerves.MethodsSeven hypertensive patients (4F:3M; 50-65 years) completed PET-CT sympathetic neuroimaging of the renal cortex using 11C-methylreboxetine (11C-MRB, norepinephrine transporter ligand) and 6-[18F]-fluorodopamine (18F-FDA; substrate for the cell membrane norepinephrine transporter) before and 8 weeks after chemical RDN (Peregrine System Infusion Catheter, Ablative Solutions; n = 4; 2F:2M) or control renal angiography (n = 3; 2F:1M). Patients completed physiological phenotyping including 24-hour ambulatory blood pressure, hemodynamics, muscle sympathetic nerve activity, and 24-hour urine collection.ResultsRDN decreased 11C-MRB-derived radioactivity by ~30% (Δ 11C-MRB/chamber: -0.95 a.u. confidence interval (CI): -1.36 to -0.54, P = 0.0002), indicative of efferent RDN. In contrast, 18F-FDA-derived radioactivity increased (Δ 18F-FDA/chamber: 2.72 a.u. CI: 0.73-4.71, P = 0.009), consistent with reduced vesicular turnover. Controls showed no change in either marker. Ambulatory systolic pressure decreased in 3 of 4 patients (-9 mm Hg CI: -27 to 9, P = 0.058), and central systolic pressure decreased in all patients (-23 mm Hg CI: -51 to 5, P = 0.095).ConclusionsThese results are the first to show efferent sympathetic denervation of the renal cortex following RDN in humans. Further studies of mechanisms underlying variable blood pressure lowering in the setting of documented RDN may provide insights into inconsistencies in clinical trial outcomes.Clinical trials registrationTrial Number NCT03465917.

| S-EPMC8351509 | biostudies-literature

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