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Current Cardiology Reports Jul 2019Interventional cardiology and in particular the field of renal denervation is subject to constant change. This review provides an up to date overview of renal... (Review)
Review
PURPOSE OF REVIEW
Interventional cardiology and in particular the field of renal denervation is subject to constant change. This review provides an up to date overview of renal denervation trials and an outlook on what to expect in the future.
RECENT FINDINGS
After the sham-controlled SYMPLICITY HTN-3 trial dampened the euphoria following early renal denervation trials, the recently published results of the sham-controlled SPYRAL HTN and RADIANCE HTN trials provided proof-of-principle for the blood pressure-lowering efficacy of renal denervation. However, these studies underline the major issue of patients' non-adherence to antihypertensive medication as well as the need for reliable patient- and procedure-related predictors of response. The second generation of sham-controlled renal denervation trials provided proof of principle for the blood pressure-lowering efficacy of RDN. However, larger trials have to assess long-term safety and efficacy.
Topics: Antihypertensive Agents; Blood Pressure; Denervation; Humans; Hypertension; Kidney; Renal Artery; Sympathectomy
PubMed: 31278490
DOI: 10.1007/s11886-019-1164-2 -
EuroIntervention : Journal of EuroPCR... Apr 2024Arterial hypertension is a global leading cause of cardiovascular, cerebrovascular, and renal disease, as well as mortality. Although pharmacotherapy is safe and...
Arterial hypertension is a global leading cause of cardiovascular, cerebrovascular, and renal disease, as well as mortality. Although pharmacotherapy is safe and effective in lowering blood pressure (BP) and cardiovascular disease risk, BP control remains poor, and the mortality rates associated with high BP have been steadily increasing. Device-based therapies have been investigated to overcome barriers to pharmacotherapy, including non-adherence and low rates of persistence to daily medications. Among these device-based therapies, catheter-based renal denervation (RDN) has been most extensively examined over the past 15 years. In this state-of-the-art article, we summarise the rationale for RDN, review the available evidence, provide recommendations for a safe procedure, and discuss the role of RDN in current guidelines and clinical practice.
Topics: Humans; Blood Pressure; Antihypertensive Agents; Sympathectomy; Treatment Outcome; Hypertension; Kidney; Denervation
PubMed: 38629418
DOI: 10.4244/EIJ-D-23-00836 -
Current Opinion in Nephrology and... Sep 2023Renal denervation represents a new dimension to hypertension treatment, with multiple device manufacturers seeking premarket FDA approval currently. Interest in the... (Review)
Review
PURPOSE OF REVIEW
Renal denervation represents a new dimension to hypertension treatment, with multiple device manufacturers seeking premarket FDA approval currently. Interest in the efficacy and safety of the treatment has spurred compelling mechanistic studies into the function of renal nerves and downstream impacts of denervation.
RECENT FINDINGS
A trial of the ultrasound Paradise Catheter system (RADIANCE II) found a 6.3 mmHg reduction in SBP relative to sham controls. A trial of the Symplicity Spyral system (SPYRAL HTN-ON MED) found an insignificant reduction in SBP relative to sham controls. Individuals were taking antihypertensive medications during the study, and investigators note the sham group experienced a larger medication burden than the denervated group. Recent preclinical studies have evaluated potential risks of renal denervation, how sympathetic activity broadly is affected, as well as identifying possible biomarkers to identify individuals where denervation would be more successful.
SUMMARY
Studies of renal denervation continue to find a robust antihypertensive effect, especially in studies wherein medications are withdrawn. Further investigation into mechanisms and indicators for usage of the technique will be important in identifying the patient population most likely to benefit from usage of renal denervation.
Topics: Humans; Hypertension; Antihypertensive Agents; Sympathectomy; Kidney; Denervation; Blood Pressure; Treatment Outcome
PubMed: 37530084
DOI: 10.1097/MNH.0000000000000908 -
Experimental Physiology Apr 2015What is the topic of this review? Does catheter-based renal denervation effectively denervate the afferent and efferent renal nerves and does reinnervation occur? What... (Review)
Review
What is the topic of this review? Does catheter-based renal denervation effectively denervate the afferent and efferent renal nerves and does reinnervation occur? What advances does it highlight? Following catheter-based renal denervation, the afferent and efferent responses to electrical stimulation were abolished, renal sympathetic nerve activity was absent, and levels of renal noradrenaline and immunohistochemistry for tyrosine hydroxylase and calcitonin gene-related peptide were significantly reduced. By 11 months after renal denervation, both the functional responses and anatomical markers of afferent and efferent renal nerves had returned to normal, indicating reinnervation. Renal denervation reduces blood pressure in animals with experimental hypertension and, recently, catheter-based renal denervation was shown to cause a prolonged decrease in blood pressure in patients with resistant hypertension. The randomized, sham-controlled Symplicity HTN-3 trial failed to meet its primary efficacy end-point, but there is evidence that renal denervation was incomplete in many patients. Currently, there is little information regarding the effectiveness of catheter-based renal denervation and the extent of reinnervation. We assessed the effectiveness of renal nerve denervation with the Symplicity Flex catheter and the functional and anatomical reinnervation at 5.5 and 11 months postdenervation. In anaesthetized, non-denervated sheep, there was a high level of renal sympathetic nerve activity, and electrical stimulation of the renal nerve increased blood pressure and reduced heart rate (afferent response) and caused renal vasoconstriction and reduced renal blood flow (efferent response). Immediately after renal denervation, renal sympathetic nerve activity and the responses to electrical stimulation were absent, indicating effective denervation. By 11 months after denervation, renal sympathetic nerve activity was present and the responses to electrical stimulation were normal, indicating reinnervation. Anatomical measures of renal innervation by sympathetic efferent nerves (tissue noradrenaline and tyrosine hydroxylase) and afferent sensory nerves (calcitonin gene-related peptide) demonstrated large decreases at 1 week postdenervation, but normal levels at 11 months postdenervation. In summary, catheter-based renal denervation is effective, but reinnervation occurs. Studies of central and renal changes postdenervation are required to understand the causes of the prolonged hypotensive response to catheter-based renal denervation in human hypertension.
Topics: Animals; Blood Pressure; Catheters; Humans; Hypertension; Kidney; Sympathectomy; Sympathetic Nervous System
PubMed: 25573386
DOI: 10.1113/expphysiol.2014.079871 -
Current Hypertension Reports Jul 2016SYMPLICITY HTN-3 was a pivotal moment for renal denervation as a treatment option for resistant hypertension. Prior unblinded studies were called into question given the... (Review)
Review
SYMPLICITY HTN-3 was a pivotal moment for renal denervation as a treatment option for resistant hypertension. Prior unblinded studies were called into question given the negative results of the first sham-controlled trial of renal denervation. Reevaluation of the renal denervation procedure demonstrated that a more precise approach was needed to adequately denervate the kidney. This new approach has been implemented in two ongoing clinical trials, one on and one off medications to assess the new procedure's efficacy and safety. These and other ongoing trials will be discussed in the context of older studies in this field. We focus on novel findings published following the release of SYMPLICITY HTN-3 data in early 2014 and look to the future of renal denervation in the treatment of primary hypertension.
Topics: Denervation; Humans; Hyperkalemia; Hypertension, Renal; Kidney; Renin-Angiotensin System; Sodium; Zirconium
PubMed: 27245681
DOI: 10.1007/s11906-016-0666-1 -
Sexual Medicine Reviews Oct 2022The management of chronic scrotal pain is long and varied, with historical treatment algorithms typically ending with orchiectomy. Microsurgical denervation of the... (Review)
Review
INTRODUCTION
The management of chronic scrotal pain is long and varied, with historical treatment algorithms typically ending with orchiectomy. Microsurgical denervation of the spermatic cord (MDSC) is a testicle-sparing option for patients who have failed conservative treatment options and over its forty-year history has seen many technical refinements.
OBJECTIVES
To review the history and development of MDSC and discuss the outcomes of different surgical techniques.
METHODS
A literature review using PubMed and Google Scholar was conducted to identify studies pertaining to surgical treatment of CSP, MDSC, and outcomes. Search terms included "chronic," "scrotal pain," "orchialgia," "spermatic cord," "denervation," and "microsurgery."
RESULTS
We included 21 case reports and series since the first seminal paper describing MDSC technique in 1978. Additional studies that challenged existing conventions or described novel techniques are also discussed. The current standard procedure utilizes a subinguinal incision and a surgical microscope. Open, robotic, and laparoscopic approaches to MDSC have been described, but access to minimally invasive instruments may be limited outside of developed nations. Pain reduction following preoperative spermatic cord predicts success of MDSC. Methods for identifying and preserving the testicular and deferential arteries vary depending on surgeon preference but appear to have comparable outcomes. Future developments in MDSC involve targeted denervation, minimizing collateral thermal injury, and alternative techniques to visualize arterial supply.
CONCLUSION
For patients suffering from CSP, MDSC is a well-studied technique that may offer appropriately selected patients' relief. Future investigation comparing targeted vs full MDSC as well as in vivo study of new techniques are needed to continue to improve outcomes. Sun HH, Tay KS, Jesse E, et al. Microsurgical Denervation of the Spermatic Cord: A Historical Perspective and Recent Developments. Sex Med Rev 2022;10:791-799.
Topics: Denervation; Genital Diseases, Male; Humans; Male; Microsurgery; Pelvic Pain; Spermatic Cord; Testicular Diseases
PubMed: 34996747
DOI: 10.1016/j.sxmr.2021.11.005 -
Hypertension Research : Official... Feb 2022Renal denervation is a promising new non-pharmacological treatment for resistant hypertension. However, there is a lack of data from Asian patients. The REQUIRE trial... (Randomized Controlled Trial)
Randomized Controlled Trial
Renal denervation is a promising new non-pharmacological treatment for resistant hypertension. However, there is a lack of data from Asian patients. The REQUIRE trial investigated the blood pressure-lowering efficacy of renal denervation in treated patients with resistant hypertension from Japan and South Korea. Adults with resistant hypertension (seated office blood pressure ≥150/90 mmHg and 24-hour ambulatory systolic blood pressure ≥140 mmHg) with suitable renal artery anatomy were randomized to ultrasound renal denervation or a sham procedure. The primary endpoint was change from baseline in 24-hour ambulatory systolic blood pressure at 3 months. A total of 143 patients were included (72 renal denervation, 71 sham control). Reduction from baseline in 24-hour ambulatory systolic blood pressure at 3 months was not significantly different between the renal denervation (-6.6 mmHg) and sham control (-6.5 mmHg) groups (difference: -0.1, 95% confidence interval -5.5, 5.3; p = 0.971). Reductions from baseline in home and office systolic blood pressure (differences: -1.8 mmHg [p = 0.488] and -2.0 mmHg [p = 0.511], respectively), and medication load, did not differ significantly between the two groups. The procedure-/device-related major adverse events was not seen. This study did not show a significant difference in ambulatory blood pressure reductions between renal denervation and a sham procedure in treated patients with resistant hypertension. Although blood pressure reduction after renal denervation was similar to other sham-controlled studies, the sham group in this study showed much greater reduction. This unexpected blood pressure reduction in the sham control group highlights study design issues that will be addressed in a new trial. CLINICAL TRIAL REGISTRATION: NCT02918305 ( http://www.clinicaltrials.gov ).
Topics: Adult; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Catheters; Denervation; Humans; Hypertension; Kidney; Sympathectomy; Treatment Outcome
PubMed: 34654905
DOI: 10.1038/s41440-021-00754-7 -
International Journal of Molecular... Mar 2023Loss of motoneuron innervation (denervation) is a hallmark of neurodegeneration and aging of the skeletal muscle. Denervation induces fibrosis, a response attributed to...
Loss of motoneuron innervation (denervation) is a hallmark of neurodegeneration and aging of the skeletal muscle. Denervation induces fibrosis, a response attributed to the activation and expansion of resident fibro/adipogenic progenitors (FAPs), i.e., multipotent stromal cells with myofibroblast potential. Using in vivo and in silico approaches, we revealed FAPs as a novel cell population that activates the transcriptional coregulators YAP/TAZ in response to skeletal muscle denervation. Here, we found that denervation induces the expression and transcriptional activity of YAP/TAZ in whole muscle lysates. Using the transgenic reporter mice to trace FAPs, we demonstrated that denervation leads to increased YAP expression that accumulates within FAPs nuclei. Consistently, re-analysis of published single-nucleus RNA sequencing (snRNA-seq) data indicates that FAPs from denervated muscles have a higher YAP/TAZ signature level than control FAPs. Thus, our work provides the foundations to address the functional role of YAP/TAZ in FAPs in a neurogenic pathological context, which could be applied to develop novel therapeutic approaches for the treatment of muscle disorders triggered by motoneuron degeneration.
Topics: Animals; Mice; Adipogenesis; Cell Differentiation; Denervation; Mice, Transgenic; Muscle, Skeletal
PubMed: 36982659
DOI: 10.3390/ijms24065585 -
Sexual Medicine Reviews Oct 2022The management of chronic scrotal pain is long and varied, with historical treatment algorithms typically ending with orchiectomy. Microsurgical denervation of the... (Review)
Review
INTRODUCTION
The management of chronic scrotal pain is long and varied, with historical treatment algorithms typically ending with orchiectomy. Microsurgical denervation of the spermatic cord (MDSC) is a testicle-sparing option for patients who have failed conservative treatment options and over its forty-year history has seen many technical refinements.
OBJECTIVES
To review the history and development of MDSC and discuss the outcomes of different surgical techniques.
METHODS
A literature review using PubMed and Google Scholar was conducted to identify studies pertaining to surgical treatment of CSP, MDSC, and outcomes. Search terms included "chronic," "scrotal pain," "orchialgia," "spermatic cord," "denervation," and "microsurgery."
RESULTS
We included 21 case reports and series since the first seminal paper describing MDSC technique in 1978. Additional studies that challenged existing conventions or described novel techniques are also discussed. The current standard procedure utilizes a subinguinal incision and a surgical microscope. Open, robotic, and laparoscopic approaches to MDSC have been described, but access to minimally invasive instruments may be limited outside of developed nations. Pain reduction following preoperative spermatic cord predicts success of MDSC. Methods for identifying and preserving the testicular and deferential arteries vary depending on surgeon preference but appear to have comparable outcomes. Future developments in MDSC involve targeted denervation, minimizing collateral thermal injury, and alternative techniques to visualize arterial supply.
CONCLUSION
For patients suffering from CSP, MDSC is a well-studied technique that may offer appropriately selected patients' relief. Future investigation comparing targeted vs full MDSC as well as in vivo study of new techniques are needed to continue to improve outcomes.
Topics: Male; Humans; Denervation; Spermatic Cord; Testicular Diseases; Genital Diseases, Male; Pelvic Pain
PubMed: 37051952
DOI: 10.1016/j.sxmr.2021.11.005 -
Current Hypertension Reports Jul 2017Device-based antihypertensive treatments have primarily been developed and clinically tested for patients with hypertension refractory to pharmacological treatment. Most... (Review)
Review
Device-based antihypertensive treatments have primarily been developed and clinically tested for patients with hypertension refractory to pharmacological treatment. Most but not all device-based treatments target the sympathetic nervous system and provided important new insight in the mechanisms of human hypertension. This review provides an overview on the scientific rational and clinical data on recent device-based antihypertensive treatment approaches. Device-based treatments targeting the sympathetic nervous system include catheter-based renal nerve ablation, electrical carotid sinus stimulation, modulation of baroreflex transduction through a dedicated carotid stent, carotid body denervation, and deep brain stimulation. Creation of a defined arteriovenous stent with a coupler device and removal of stimulatory antibodies against alpha adrenoreceptors have also been tested. The clinical evidence differs from therapy to therapy with the largest dataset for renal nerve ablation followed by electrical carotid sinus stimulation. Yet, none has been proven efficacious in sham-controlled clinical trials, and none has been shown to reduce cardiovascular morbidity or mortality. Before efficacy is proven, these treatments should not be part of routine medical care and only be applied in the setting of clinical studies.
Topics: Blood Pressure; Catheter Ablation; Denervation; Electric Stimulation Therapy; Humans; Hypertension; Stents; Sympathetic Nervous System
PubMed: 28620841
DOI: 10.1007/s11906-017-0755-9