Renal sympathetic denervation for blood pressure control: a review of the current evidence and ongoing studies.
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ABSTRACT:
SUBMITTER: Todoran TM
PROVIDER: S-EPMC8031833 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundRecent trials support the efficacy of renal sympathetic denervation (RDN) to reduce blood pressure (BP). Nevertheless, about one third of patients are considered non-responders to RDN. Previous retrospective analyses suggest arterial stiffness could predict BP response to RDN.AimsWe prospectively assessed the potential of invasive pulse wave velocity (iPWV) to predict BP response to RDN. Additionally, we aimed to establish non-invasive models based on arterial stiffness to predict BP response to RDN.Methods iPWV, magnetic resonance imaging-based markers of arterial stiffness and the carotid-femoral pulse wave velocity were recorded prior to RDN in patients with treatment resistant hypertension. Changes in daytime BP after 3 months were analysed according to the prespecified iPWV cut-off (14.4 m/s). Regression analyses were used to establish models for non-invasive prediction of BP response. Results were compared to iPWV as reference and were then validated in an external patient cohort.ResultsEighty patients underwent stiffness assessment before RDN. After 3 months, systolic 24h and daytime BP were reduced by 13.6±9.8 mmHg and 14.7±10.6 mmHg in patients with low iPWV, versus 6.2±13.3 mmHg and 6.3±12.8 mmHg in those with high iPWV (p<0.001 for both). Upon regression analysis, logarithmic ascending aortic distensibility and systolic baseline BP independently predicted BP change at follow-up. Both were confirmed in the validation cohort.Conclusions iPWV is an independent predictor for BP response after RDN. In addition, BP change prediction following RDN using non-invasive measures is feasible. This could facilitate patient selection for RDN treatment.
| S-EPMC10241279 | biostudies-literature
Project description: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.
| S-EPMC5808654 | biostudies-literature
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.
| S-EPMC3927110 | biostudies-literature
Project description:BACKGROUND Catheter-based renal sympathetic denervation has been reported to be effective for treatment resistance hypertension in Australia and Europe. However, in the blinded SYMPLICITY HTN-3 trial, renal denervation did not achieve a significant decrease in blood pressure (BP) in comparison to sham controls. There have been various discussions on the factors that influenced this result. CASE REPORT Two men on antihypertensive therapy underwent unilateral radical nephroureterectomy for cancer of the renal pelvis. When the renal artery adventitia was stripped and cauterized just before renal artery ligation, the measured BP of the 2 men increased after stripping adventitia and decreased gradually after cauterization of the renal artery. This was presumably due to removal of renal artery sympathetic nerves, similar to the mechanism of catheter-based renal sympathetic denervation, although anesthesia, fluid infusion, and/or mesenteric traction may have had an influence. CONCLUSIONS A similar strategy involving thoracolumbar sympathectomy was reported about 50 years ago. The clinically significant blood pressure reduction in these patients suggests renal denervation is effective.
| S-EPMC5983072 | biostudies-literature
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
Project description:Hypertension is one of the most prevalent chronic diseases worldwide and the incidence of resistant hypertension is increasing. Catheter-based renal denervation (RDN) offers a new approach to reaching blood pressure goals by targeting the renal nerves. The technique has demonstrated significant and sustained reductions in blood pressure (BP) in the Symplicity HTN-1 and Symplicity HTN-2 clinical trials. The Global SYMPLICITY Registry aims to demonstrate safety and effectiveness in a 'real-world' patient population. Real-world RDN experience has emphasised that patient selection is crucial to successful outcomes; a multidisciplinary referral network is recommended to increase awareness of the procedure and identify patients who are likely to respond best to RDN. Further advances in catheter technology have led to the development of the multi-electrode Symplicity Spyral™ multi-electrode catheter; preliminary data from the feasibility study using the Symplicity Spyral catheter indicate clinical efficacy and procedural safety with reduced procedure times. The Symplicity Spyral catheter is not yet commercially available. The indications of RDN may also expand beyond resistant hypertension - encouraging data have been seen in patients with moderate treatment resistant hypertension. Furthermore, RDN may be beneficial in other clinical states characterised by sympathetic nervous system overactivation including heart failure and chronic kidney disease. Additional data are needed to evaluate the efficacy of RDN in these disease states.
| S-EPMC5808595 | biostudies-other
Project description: Not available
| S-EPMC6034470 | biostudies-literature
Project description:BackgroundWhether renal denervation (RDN) in patients with resistant hypertension normalizes blood pressure (BP) regulation in response to routine cardiovascular stimuli such as upright posture is unknown. We conducted an integrative study of BP regulation in patients with resistant hypertension who had received RDN to characterize autonomic circulatory control.MethodsTwelve patients (60 ± 9 [SD] years, n = 10 males) who participated in the Symplicity HTN-3 trial were studied and compared to 2 age-matched normotensive (Norm) and hypertensive (unmedicated, HTN) control groups. BP, heart rate (HR), cardiac output (Qc), muscle sympathetic nerve activity (MSNA), and neurohormonal variables were measured supine, and 30° (5 minutes) and 60° (20 minutes) head-up-tilt (HUT). Total peripheral resistance (TPR) was calculated from mean arterial pressure and Qc.ResultsDespite treatment with RDN and 4.8 (range, 3-7) antihypertensive medications, the RDN had significantly higher supine systolic BP compared to Norm and HTN (149 ± 15 vs. 118 ± 6, 108 ± 8 mm Hg, P < 0.001). When supine, RDN had higher HR, TPR, MSNA, plasma norepinephrine, and effective arterial elastance compared to Norm. Plasma norepinephrine, Qc, and HR were also higher in the RDN vs. HTN. During HUT, BP remained higher in the RDN, due to increases in Qc, plasma norepinephrine, and aldosterone.ConclusionWe provide evidence of a possible mechanism by which BP remains elevated post RDN, with the observation of increased Qc and arterial stiffness, as well as plasma norepinephrine and aldosterone levels at approximately 2 years post treatment. These findings may be the consequence of incomplete ablation of sympathetic renal nerves or be related to other factors.
| S-EPMC5861553 | biostudies-literature
Project description:BackgroundSympathetic overactivity has been linked to vasospastic angina (VSA), although the exact pathophysiology of VSA is poorly understood. The purpose of this study is to assess if renal sympathetic denervation (RDN) reduces cardiac sympathetic nerve activity with a subsequent beneficial effect on angina relief in patients with refractory VSA.Methods and resultsCardiac sympathetic nerve activity was assessed prior to procedure and at 6 months post-procedure using iodine-123 labeled meta-iodobenzylguanidine (123I-MIBG) imaging. The Seattle Angina questionnaire (SAQ) was used to assess the degree to which the disease impacts quality of life. No significant change was observed in early HMR (pre-RDN: 2.74 [2.10 to 3.21] vs 6 months post-RDN: 2.57 [2.20 to 3.00]; P = 0.76), and late HMR (pre-RDN: 2.56 [2.18 to 3.20] vs 6 months post-RDN: 2.36 [2.13 to 3.22]; P = 0.22). Additionally, no change was seen in WR (P = 0.22). SAQ results revealed significant improvements in perceived physical limitation, angina frequency, and quality of life at 6 months (P < 0.05 for all).ConclusionRDN resulted in improvements in angina class and quality of life at 6 months in patients with refractory VSA. RDN, however, did not result in significant changes in cardiac sympathetic nerve activity as measured using 123I-MIBG. The latter observation should be considered with caution given the small sample size of this study. Larger studies are needed to assess this further.
| S-EPMC7749092 | biostudies-literature
Project description:Studies on the blood pressure lowering effect of renal denervation (RDN) in resistant hypertensive patients have produced conflicting results. Change in medication usage during the studies may be responsible for this inconsistency. To eliminate the effect of medication usage on blood pressure we focused on unmedicated hypertensive patients who underwent RDN.Our study reports on a cohort of patients, who were not on blood pressure lowering drugs at baseline and during follow-up, from eight tertiary centers. Data of patients were used when they were treated with RDN and had a baseline office systolic blood pressure (SBP) ?140 mmHg and/or 24-h ambulatory SBP ?130 mmHg. Our primary outcome was defined as change in office and 24-h SBP at 12 months after RDN, compared to baseline. Fifty-three patients were included. There were three different reasons for not using blood pressure lowering drugs: (1) documented intolerance or allergic reaction (57 %); (2) temporary cessation of medication for study purposes (28 %); and (3) reluctance to take antihypertensive drugs (15 %). Mean change in 24-h SBP was -5.7 mmHg [95 % confidence interval (CI) -11.0 to -0.4; p = 0.04]. Mean change in office SBP was -13.1 mmHg (95 % CI -20.4 to -5.7; p = 0.001). No changes were observed in other variables, such as eGFR, body-mass-index and urinary sodium excretion.This explorative study in hypertensive patients, who are not on blood pressure lowering drugs, suggests that at least in some patients RDN lowers blood pressure.
| S-EPMC4989018 | biostudies-literature