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American Journal of Hypertension Jun 2011Essential hypertension remains one of the biggest challenges in medicine with an enormous impact on both individual and society levels. With the exception of relatively... (Review)
Review
Essential hypertension remains one of the biggest challenges in medicine with an enormous impact on both individual and society levels. With the exception of relatively rare monogenetic forms of hypertension, there is now general agreement that the condition is multifactorial in nature and hence requires therapeutic approaches targeting several aspects of the underlying pathophysiology. Accordingly, all major guidelines promote a combination of lifestyle interventions and combination pharmacotherapy to reach target blood pressure (BP) levels in order to reduce overall cardiovascular risk in affected patients. Although this approach works for many, it fails in a considerable number of patients for various reasons including drug-intolerance, noncompliance, physician inertia, and others, leaving them at unacceptably high cardiovascular risk. The quest for additional therapeutic approaches to safely and effectively manage hypertension continues and expands to the reappraisal of older concepts such as renal denervation. Based on the robust preclinical and clinical data surrounding the role of renal sympathetic nerves in various aspects of BP control very recent efforts have led to the development of a novel catheter-based approach using radiofrequency (RF) energy to selectively target and disrupt the renal nerves. The available evidence from the limited number of uncontrolled hypertensive patients in whom renal denervation has been performed are auspicious and indicate that the procedure has a favorable safety profile and is associated with a substantial and presumably sustained BP reduction. Although promising, a myriad of questions are far from being conclusively answered and require our concerted research efforts to explore the full potential and possible risks of this approach. Here we briefly review the science surrounding renal denervation, summarize the current data on safety and efficacy of renal nerve ablation, and discuss some of the open questions that need to be addressed in the near future.
Topics: Aged; Animals; Blood Pressure; Cardiovascular Diseases; Catheter Ablation; Denervation; Humans; Hypertension; Kidney; Middle Aged; Risk; Sympathectomy; Sympathetic Nervous System
PubMed: 21394087
DOI: 10.1038/ajh.2011.35 -
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 -
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 -
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 -
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 -
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 -
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 -
Cardiovascular Revascularization... Sep 2022Radio frequency (RF) based percutaneous catheter renal denervation systems offer an additional clinical tool, along with lifestyle modification and drug therapy, to... (Review)
Review
Radio frequency (RF) based percutaneous catheter renal denervation systems offer an additional clinical tool, along with lifestyle modification and drug therapy, to address the global epidemic of uncontrolled hypertension. The most widely applied RF system has been designed to optimize both procedural and safety and efficacy. Lesion size, shape, and depth result from a complex interaction of device design, anatomy, and tissue electrical conduction properties. Power control algorithms must be carefully designed, incorporating feedback to maximize nerve destruction while minimizing collateral damage. Physical and numerical modelling as well as analysis of sensor feedback provide insight into design performance that cannot be derived from clinical trials. This review is focused on key design and performance aspects of the most widely applied renal denervation system meant to optimize safety and efficacy of the procedure.
Topics: Blood Pressure; Catheter Ablation; Catheters; Denervation; Electric Impedance; Humans; Hypertension; Kidney; Renal Artery; Sympathectomy; Temperature; Treatment Outcome
PubMed: 35232663
DOI: 10.1016/j.carrev.2022.02.018 -
Physiological Reports May 2023Skeletal muscle is a highly pliable tissue and various adaptations such as muscle hypertrophy or atrophy are induced by overloading or disuse, respectively. However, the...
Skeletal muscle is a highly pliable tissue and various adaptations such as muscle hypertrophy or atrophy are induced by overloading or disuse, respectively. However, the combined effect of overloading and disuse on the quantitative adaptation of skeletal muscle is unknown. Thus, the aim of this study was to investigate the effects of the combined stimuli of overloading and disuse on mouse skeletal muscle mass and the expression of regulatory factors for muscle protein anabolism or catabolism. Male mice from the Institute Cancer Research were subjected to denervation concomitant with unilateral functional overload or functional overload concomitant with unilateral denervation. Disuse and functional overload were induced by sciatic nerve transection (denervation) and synergist ablation, respectively, and the plantaris muscle was harvested 14 days after the operation. Our results showed that denervation attenuated functional overload-induced muscle hypertrophy and functional overload partially ameliorated the denervation-induced muscle atrophy. P70S6K phosphorylation, an indicator of mechanistic target of rapamycin complex 1 (mTORC1) activation, was not increased by unilateral functional overload in denervated muscles or by unilateral denervation in functional overloaded muscles. Denervation did not affect the increase of LC3-II, a marker of autophagy activation, and ubiquitinated protein expression upon unilateral functional overload. Also, functional overload did not affect ubiquitinated protein expression during unilateral denervation. Thus, our findings suggest that functional overload-induced muscle hypertrophy or denervation-induced muscle atrophy was attenuated by the combined stimuli of overload and denervation.
Topics: Male; Animals; Mice; Muscle, Skeletal; Transcription Factors; Muscular Atrophy; Denervation; Hypertrophy
PubMed: 37161590
DOI: 10.14814/phy2.15689