Effect Of Catheter-based Renal Denervation Research Articles

F-3 | The Effect Of Catheter-Based Renal Denervation On Cardiovascular Outcomes and Atrial Fibrillation In Recent Clinical Trials: A Systematic Review

F-3 | The Effect Of Catheter-Based Renal Denervation On Cardiovascular Outcomes and Atrial Fibrillation In Recent Clinical Trials: A Systematic Review

ENDOVASCULAR RADIOFREQUENCY RENAL DENERVATION IN DIFFICULT TO TREAT ARTERIAL HYPERTENSION: A SINGLE CENTER EXPERIENCE

Objective: To assess safety and effectiveness of catheter-based renal denervation (RDN) for reduction of blood pressure (BP) in patients with difficult to treat arterial hypertension. Design and method: Thirtyfive patients selected with difficult to treat arterial hypertension, underwent RDN. Secondary forms of hypertension were excluded, and an appropriate renal artery anatomy was confirmed in all patients. Every patient underwent follow-up at 30 days, and then every 12 months, consisting in clinical examination, office BP measurements, ambulatory blood pressure monitoring, and biochemical analysis. At 12 months tansthoracic echocardiography and renal duplex sonography were performed. Results: The median value of systolic clinic BP decreased from 161 mmHg (25th-75th percentiles 158 - 191) at baseline to 144 mmHg (25th-75th percentiles 136 - 153) at follow up (p= 0.012), and the median value of diastolic clinic BP decreased from 102 mmHg (25th-75th percentiles 94 - 122) at baseline to 90 mmHg (25th-75th percentiles 78 - 99) at follow-up (p= 0.012). The number of medications changed from 5 (range 2-8) at baseline to 3.3 (range 0-6) at follow up. A significant decrease of left ventricular mass index from a median of 160 g/m2 (25th-75th percentiles 147 - 151) at baseline to 126 g/m2 (25th-75th percentiles 107 - 151) at follow-up (p= 0.043) was detected. The renal function did not demonstrate significant changes, however plasma renin activity and HOMA index were significantly reduced. No periprocedural or long term complications were observed. Conclusions: Our data confirm that RDN may constitute an effective and safe therapeutic choice for the treatment of difficult to treat hypertension.

Renal, Cardiac, and Autonomic Effects of Catheter-Based Renal Denervation in Ovine Heart Failure.

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Effects of catheter-based renal denervation on glycemic control and lipid levels: a systematic review and meta-analysis.

As an emerging interventional technique to treat resistant hypertension, renal denervation (RDN) has also attracted considerable attention due to its potential beneficial effects on glucose and lipid metabolism. Given that inconsistent results were documented among studies, we aimed to perform a systematic review and meta-analysis to elaborate on this issue. The PubMed, EMBASE, Web of Science (SCI) and ClinicalTrials.gov databases were comprehensively searched from their inception date to June 18, 2020, for relevant clinical studies evaluating the efficacy of RDN on glucose and lipid levels. The outcomes of interest were changes in fasting glucose, insulin, C-peptide, hemoglobin A1C (HbA1C), homeostatic model assessment-insulin resistance (HOMA-IR), cholesterol and triglyceride (TG) levels before versus after RDN and also RDN versus the control group. The mean differences (MDs) of the outcomes measured before versus after RDN and RDN versus the control group were pooled by a randomized effects model. Heterogeneity was quantified with Chi-square (χ2) and inconsistency index (I2). Assessment of publication bias was performed by the funnel plot and Egger's test. A total of 1600 studies were initially identified. Nineteen of the identified studies (six randomized controlled studies, one non-randomized controlled studies and 12 observational cohort studies) involving 2245 subjects were included in the final analysis. No significant change was observed after RDN in fasting glucose (weighted mean difference [WMD] - 0.19mmol/L; 95% CI - 0.37, 0.00mmol/L), insulin (standardized mean difference [SMD] - 0.01; 95% CI - 0.41, 0.39), C-peptide (SMD - 0.05; 95% CI - 0.30, 0.21), HbA1C (SMD - 0.05; 95% CI - 0.17, 0.07), HOMA-IR (SMD - 0.29; 95% CI - 0.72, 0.14), total cholesterol (TC) (WMD - 0.11mmol/L; 95% CI - 0.37, 0.15mmol/L), and low-density lipoprotein cholesterol (LDL-C) levels (WMD - 0.18mmol/L; 95% CI - 0.59, 0.24mmol/L) during follow-up. Changes in fasting glucose, insulin, HbA1C and TC levels in RDN groups were not significantly different from those in the control group. High-density lipoprotein cholesterol (HDL-C) and TG were slightly improved after RDN (WMD 0.07mmol/L, 95% CI 0.01, 0.14mmol/L; WMD - 0.26mmol/l, 95% CI - 0.51, - 0.01mmol/L, respectively). The funnel plot and Egger's test demonstrated the absence of potential publication bias. Catheter-based RDN appeared to have no impact on glucose metabolism. There was a statistically significant but clinically negligible improvement in HDL-C and TG levels based on the current evidence. Future research with more rigorous designs is warranted to draw definitive conclusions. The protocol of this meta-analysis was registered on PROSPERO (CRD42020192805). ( https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=192805 ).

Comparison of a 5 F Microtube-Irrigated Ablation Catheter and a General Ablation Catheter in the Treatment of Resistant Hypertension with Renal Denervation

Objective: To assess the effectiveness of catheter-based renal denervation for reducing blood pressure in patients with resistant hypertension using a 5 F microtube-irrigated ablation catheter. Methods: Sixty patients with resistant hypertension were divided into two groups: a microtube-irrigated ablation catheter group and a general ablation catheter group. We conducted 12-month follow-up of all patients and recorded clinical blood pressure, ambulatory blood pressure, medication use, and biochemistry test results in both groups at the baseline and at the 12-month follow-up. Results: All patients underwent renal denervation. At the 6-month follow-up, ambulatory blood pressure in the microtube-irrigated ablation catheter group was significantly lower than in the general ablation catheter group (systolic blood pressure 142.0 ± 14.4 mmHg vs. 150.8 ± 17.9 mmHg, P=0.04; diastolic blood pressure 81.2 ± 7.0 mmHg vs. 87.6 ± 8.0 mmHg, P=0.002). At the 12-month follow-up, the between-group difference in ambulatory blood pressure was not statistically significant. At the 12-month follow-up, the number of antihypertensive drugs and diuretics used in the microtube-irrigated ablation catheter group was less than in the general ablation catheter group (P=0.043). There was no statistical difference between the two groups in the results of biochemistry tests and echocardiography. Conclusion: The microtube-irrigated ablation catheter is more effective in treating hypertension than the general ablation catheter at the 6-month follow up and thus fewer antihypertensive drugs were used in the microtube-irrigated ablation catheter group than in the general ablation catheter group.

A drug-induced hypotensive challenge to verify catheter-based radiofrequency renal denervation in an obese hypertensive swine model

ObjectiveSham-controlled trials provided proof-of-principle for the blood pressure-lowering effect of catheter-based renal denervation (RDN). However, indicators for the immediate assessment of treatment success are lacking. This study sought to investigate the impact of RDN on renal renin arteriovenous difference (renal renin AV-Δ) following a hypotensive challenge (HC).MethodsTwelve hypertensive Ossabaw swine underwent either combined surgical and chemical (n = 3) or catheter-based RDN (n = 9). A telemetry monitor was implanted to acquire hemodynamic data continuously. Before and after RDN, a sodium nitroprusside-induced HC was performed. Renal renin AV-Δ was calculated as the difference of plasma renin concentrations drawn from the renal artery and vein.ResultsIn total, complete renal renin AV data were obtained in eight animals at baseline and six animals at baseline and 3 months of follow-up. Baseline renal renin AV-Δ correlated inversely with change in 24-h minimum systolic (− 0.764, p = 0.02), diastolic (r = − 0.679, p = 0.04), and mean (r = − 0.663, p = 0.05) blood pressure. In the animals with complete renin secretion data at baseline and follow-up, the HC increased renal renin AV-Δ at baseline, while this effect was attenuated following RDN (0.55 ± 0.34 pg/ml versus − 0.10 ± 0.16 pg/ml, p = 0.003). Renin urinary excretion remained unchanged throughout the study (baseline 0.286 ± 0.187 pg/ml versus termination 0.305 ± 0.072 pg/ml, p = 0.789).ConclusionRenin secretion induced by HC was attenuated following RDN and may serve as an indicator for patient selection and guide successful RDN procedures.

Effects of catheter-based renal denervation on heart failure with reduced ejection fraction: a meta-analysis of randomized controlled trials.

Despite the major progress in the treatment of heart failure, the burden of heart failure is steadily increasing in the Western world. Heart failure is characterized by increased sympathetic activity, and chronic sympathetic activation is involved in the maintenance of the pathological state. Recent studies have shown that catheter-based renal denervation (RDN) presents a safe and minimally invasive treatment option for uncontrolled hypertension, a condition that is driven by increased sympathetic activity. Although randomized controlled trials (RCTs) have examined the effect of RDN in heart failure patients, results are inconsistent due partly to limited power with small sample sizes. We aimed to conduct a meta-analysis of RCTs on the effect of RDN in heart failure patients with reduced left ventricular (LV) ejection fraction (EF). Electronic search identified 5 RCTs including 177 patients. In the pooled analysis, RDN increased LVEF (weighted mean difference (WMD) [95% CI] = 6.289 [1.883, 10.695]%) and 6-min walk distance (61.063 [24.313, 97.813]m) and decreased B-type natriuretic peptide levels (standardized mean difference [95% CI] = - 1.139 [- 1.824, - 0.454]) compared with control. In contrast, RDN did not significantly change estimated glomerular filtration rate (WMD [95% CI] = 5.969 [- 2.595, 14.533]ml/min/1.73m2) and systolic (- 1.991 [- 15.639, 11.655]mmHg) or diastolic (- 0.003 [- 10.325, 10.320]mmHg) blood pressure compared with control. Our meta-analysis suggests that RDN may improve LV function and exercise capacity in heart failure patients with reduced EF, providing the rationale to conduct large-scale multicenter trials to confirm the observed potential benefits of RDN.

TCT-83 Effects of Catheter-Based Renal Denervation on Left Ventricular Function Assessed by 2-Dimensional Speckle Tracking Echocardiography

Catheter-based renal denervation (RDN) has been shown to reduce sympathetic activity and blood pressure (BP) by affecting renal sympathetic nerves. However, the effects of RDN on contractility are unknown. In this prospective single-center trial, patients age 18 to 80 years underwent radiofrequency

Effect of Catheter-Based Renal Denervation on Uncontrolled Hypertension: A Systematic Review and Meta-analysis

ObjectiveTo assess the efficacy and safety of catheter-based renal denervation (RDN) for the treatment of uncontrolled hypertension by conducting a systematic review and a meta-analysis. MethodsThe Medline, Cochrane Library, and Embase databases were searched for clinical studies between January 1, 2009, and July 16, 2018. Studies that evaluated the effect of RDN on uncontrolled hypertension were identified. The primary endpoints were changes in 24-hour ambulatory systolic blood pressure (BP) and office systolic BP. The secondary endpoints included changes in 24-hour ambulatory diastolic BP, office diastolic BP, and major adverse events. ResultsAfter a literature search and detailed evaluation, 12 randomized controlled trials with a total of 1539 individuals were included in the quantitative analysis. Pooled analyses indicated that RDN was associated with a significantly greater reduction of 24-hour systolic BP (mean difference [MD], −4.02 mm Hg; 95% CI, −5.49 to −2.56; P<.001) and office systolic BP (MD, −8.93 mm Hg; 95% CI, −14.03 to −3.83; P<.001) than controls. Similarly, RDN significantly reduced 24-hour diastolic BP (MD, −2.05 mm Hg; 95% CI, −3.05 to −1.05; P<.001) and office diastolic BP (MD, −4.49 mm Hg; 95% CI, −6.46 to −2.52; P<.001). RDN was not associated with an increased risk of major adverse events (relative risk, 1.06; 95% CI, 0.72 to 1.57; P=.76). ConclusionsCatheter-based RDN was associated with a significant BP-lowering benefit without increasing major adverse events.

TCTAP A-079 True Effect of Catheter-based Renal Denervation Across a Broad Spectrum of Patients: A Systematic Review and Meta-analysis

Catheter-based renal denervation (RDN) offers a potential treatment option for patients with mild to moderate or resistant hypertension. However, randomized controlled trials (RCTs) showed inconsistent data on blood pressure (BP) reduction. The true BP-lowering effects of RDN might have been

Abstract 20949: Impact of Renal Denervation on Autonomic Nerve Activity

Introduction: Recent studies reported potential antiarrhythmic effect of catheter-based renal denervation (RDN). We sought to evaluate impacts of RDN on cardiac autonomic nerve activity in ambulatory canine model. Methods: Telemetry devices (D70-EEE, DSI) were implanted in 17 mongrel dogs to record ambulatory nerve activity simultaneously from left stellate ganglion (SG), superior left ganglionated plexus (SLGP), and left renal nerve. After 1 week of baseline nerve activity recording, RDN was performed at both renal arteries using a specialized catheter (Symplicity TM , Medtronic) (n=10). A control animals underwent autonomic nerve recording operation but with sham procedure (n=3). Bilateral surgical stripping of the renal nerve adventitia was performed in 4 dogs (n=4, surgical RDN). One-minute integrated nerve activities were quantified and compared among groups up to 2 weeks. Results: Renal nerve acvitivity (RNA) decreased after catheter RDN (-6.7±13.4% from baseline), while RNA increased after sham operation by 7.4±9.5% (p=0.103). After surgical RDN, no RNA was observed. In contrast to the increased SG nerve activity (SGNA) after sham operation (+2.2±11.4%), SGNA decreased after catheter RDN (-2.1±10.8%, p=0.073) and surgical RDN (-10.6±13.1%, p=0.061 vs. control). SLGP nerve activity (SLGPNA) also increased by 7.1±3.1% after sham operation, while SLGPNA decreased after catheter-based (-8.1±13.9%, p=0.008), and surgical RDN (-6.3±10.2%, p=0.073 vs. control). Immunohistochemistry showed increment of TH (tyrosine hydroxylase)-negative cells in SG after RDN (% of TH-negative cells: control=1.8%, catheter RDN=5.5% [p=0.058 vs. control], surgical RDN=7.35% [p=0.039, vs. control]). Conclusions: The response of renal nerve and cardiac autonomic nerve activity to catheter based RDN was diverse. Renal denervation decreased SGNA and SLGPNA, with neural remodeling at SG. These results may support anti-arrhythmic effects of RDN.

Renal safety of catheter-based renal denervation: systematic review and meta-analysis.

Catheter-based renal denervation (RDN) is a possible treatment to lower blood pressure. The invasive nature of RDN and the use of contrast agents raise concerns about potential consequent kidney damage. Our objective was to determine the change in renal function after RDN by performing a systematic review on hypertensive patients treated with RDN. A systematic search was performed in the Embase and MEDLINE databases to identify studies reporting on the effects of catheter-based RDN on renal outcome. Studies published between January 2009 and May 2016, irrespective of study design, device used or indication for treatment were included. We performed random effects meta-analyses on the change in estimated glomerular filtration rate (eGFR), serum creatinine, serum cystatin C and albumin:creatinine ratio after RDN. We only extracted and meta-analysed data from patients treated with RDN. From 1034 citations, 52 studies (38 cohort studies, 4 non-randomized comparative studies and 10 randomized controlled trials) reporting on 56 RDN cohorts were included in meta-analyses and another 14 studies in a qualitative review. Of these 56 cohorts, 48 were specifically eligible for determining the change in eGFR after RDN, totaling 2381 patients. There was no statistically significant change in eGFR after a mean follow-up time of 9.1 ± 7.0 months [0.64 mL/min/1.73 m 2 (95% confidence interval -0.47 to 1.76), P = 0.26]. The pooled mean change in serum creatinine and the results of the qualitative review further supported these findings. Based on meta-analyses of 52 studies and a qualitative review of an additional 14 studies, reporting on 2898 patients in total, we conclude that renal function does not significantly change up to at least 9 months after RDN.

Effects of catheter-based renal denervation on heart failure with reduced ejection fraction: a systematic review and meta-analysis.

Despite the recent advances in the management of heart failure, the mortality of heart failure patients remains high. It is of urgent need to develop new therapy for heart failure. Heart failure is characterized by increased sympathetic activity, and chronic sympathetic activation is involved in the maintenance of the pathological state. Catheter-based renal denervation (RDN) has emerged as an invasive but safe approach that can reduce sympathetic activation. Studies have reported inconsistent results regarding the effect of RDN in heart failure patients due to limited power with small sample sizes. We aimed to conduct a meta-analysis of the effect of RDN on heart failure patients with reduced left ventricular (LV) ejection fraction (EF). An electronic search for studies examining the effect of RDN on LV function in heart failure patients with reduced EF was conducted. Two controlled (80 patients) and 2 uncontrolled studies (21 patients) were included in this meta-analysis. In the pooled analysis, 6months after RDN, there was a greater increase in EF (weighted mean difference [95% CI]=8.63 [6.02, 11.24] %) and a greater decrease in LV end-diastolic diameter (-0.58 [-0.83, -0.34] cm) in RDN group than in control group. No serious adverse events such as acute renal artery stenosis and dissection occurred. Our meta-analysis of feasibility studies suggests that RDN may improve LV function in heart failure patients with reduced EF, providing the rationale to conduct next phase trials to confirm the observed potential benefits of RDN.

Effect of catheter-based renal denervation on left ventricular function, mass and (un)twist with two-dimensional speckle tracking echocardiography

BackgroundSpeckle tracking echocardiography (STE) is an echocardiography modality that is able to measure left ventricular (LV) characteristics, including rotation, strain and strain rate. Strain measures myocardial fibre contraction and relaxation. This study aims to assess the effect of renal sympathetic denervation (RDN) on functional myocardial parameters, including STE, and to identify potential differences between responders and non-responders.MethodsThe study population consisted of 31 consecutive patients undergoing RDN in the context of treatment for resistant hypertension. Patients were included between December 2012 and June 2014. Transthoracic echocardiography and speckle tracking analysis was performed at baseline and at 6 months follow-up.ResultsThe study population consisted of 31 patients with treatment-resistant hypertension treated with RDN (mean age 64 ± 10 years, 15 men). The total study population could be divided into responders (n = 19) and non-responders (n = 12) following RDN. RDN reduced office blood pressure by 18.9 ± 26.8/8.5 ± 13.5 mmHg (p < 0.001). A significant decrease was seen in LV posterior wall thickness (LVPWd) (0.47 ± 1.0 mm; p = 0.020), without a significant change in the LV mass index (LVMI). In the total cohort, only peak late diastolic filling velocity (A-wave velocity) decreased significantly by 5.3 ± 13.2 cm/s (p = 0.044) and peak untwisting velocity decreased significantly by 14.5 ± 28.9°/s (p = 0.025).ConclusionRDN reduced blood pressure and significantly improved functional myocardial parameters such as A-wave velocity and peak untwisting velocity in patients with treatment-resistant hypertension, suggesting a potential beneficial effect of RDN on myocardial mechanics.

Reduced blood pressure-lowering effect of catheter-based renal denervation in patients with isolated systolic hypertension: data from SYMPLICITY HTN-3 and the Global SYMPLICITY Registry.

AimsCatheter-based renal artery denervation (RDN) has been shown to lower blood pressure (BP) in certain patients with uncontrolled hypertension. Isolated systolic hypertension (ISH) (systolic BP [SBP] ≥140 mmHg and diastolic BP <90 mmHg), characterized by increased vascular stiffness, is the predominant hypertensive phenotype in elderly patients. This study compared baseline characteristics and SBP change at 6 months between patients with ISH and combined systolic–diastolic hypertension (CH).Methods and resultsThis study pooled data from 1103 patients from SYMPLICITY HTN-3 and the Global SYMPLICITY Registry. A total of 429 patients had ISH, and 674 had CH. Patients with ISH were significantly older than those with CH (66 vs. 55 years), had more type 2 diabetes mellitus (52.9 vs. 34.6%), and a lower estimated glomerular filtration rate (71.8 vs. 78.6 mL/min/1.73 m2); all P < 0.001. At 6 months, the SBP drop for CH patients was −18.7 ± 23.7 mmHg compared with a reduction of −10.9 ± 21.7 mmHg for ISH patients −7.8 mmHg, 95% confidence interval, CI, −10.5, −5.1, P < 0.001). The change in 24-h SBP at 6 months was −8.8 ± 16.2 mmHg in patients with CH vs. −5.8 ± 15.4 mmHg in ISH (−3.0 mmHg, 95% CI −5.4, −0.6, P = 0.015). Presence of ISH at baseline but not age was associated with less pronounced BP changes following the procedure. The strongest predictor of office SBP reduction at 6 months was CH, followed by aldosterone antagonist use and non-use of vasodilators.ConclusionThe reduction in BP among patients with ISH following RDN was less pronounced than the reduction in patients with CH.Clinical.Trials.gov identifiersNCT01534299 and NCT01418261.

Effect of Catheter-Based Renal Denervation on Morning and Nocturnal Blood Pressure: Insights From SYMPLICITY HTN-3 and SYMPLICITY HTN-Japan.

High nighttime and early morning blood pressure (BP) have been associated with greater risk for cardiovascular events than high clinic or daytime BP. BP is typically highest in the rising hours, when morning activities typically begin. We examined the effect of renal denervation on morning (6:00-8:59 AM), daytime (9:00 AM-8:59 PM), and nighttime (1:00-5:59 AM) ambulatory BP. Patient data from 2 prospective, randomized controlled trials of patients with treatment-resistant, uncontrolled hypertension, one conducted in a US population (Renal Denervation in Patients With Uncontrolled Hypertension [SYMPLICITY HTN-3]) and the other in a Japanese population (SYMPLICITY HTN-Japan [HTN-Japan]), were analyzed. Patients in SYMPLICITY HTN-3 and HTN-Japan were prescribed a similar number of baseline antihypertensive medications (5.2±1.4 versus 4.9±1.6, P=0.28), but the classes prescribed and changes in prescription varied by study. Among patients treated with renal denervation, although the number of ablation treatments were similar in both studies (11.2±2.8 versus 11.5±1.9, P=0.55), patients in SYMPLICITY HTN-3 were less likely to receive at least 1 four-quadrant ablation treatment (25% versus 82%, P<0.001). In SYMPLICITY HTN-3, compared with controls (n=159), patients treated with renal denervation (n=325) experienced a significantly greater change in morning (-7.3±19.8 mm Hg, P<0.001) and nighttime (-6.1±18.2 versus -1.6±19.7 mm Hg, P=0.02) but not daytime systolic BP (-7.2±16.2 versus -6.4±18.6 mm Hg, P=0.67). This same trend was observed in the pooled analysis with HTN-Japan. Reduction of BP during these high-risk periods might provide cardiovascular protection in drug-resistant hypertensive patients, although this will need to be proved in future randomized trials. URL: www.clinicaltrials.gov; Unique identifiers: NCT01418261 (SYMPLICITY HTN-3) and NCT01644604 (HTN-Japan).

Effects of catheter-based renal denervation on cardiac sympathetic activity and innervation in patients with resistant hypertension.

To investigate, whether renal denervation (RDN) has a direct effect on cardiac sympathetic activity and innervation density. RDN demonstrated its efficacy not only in reducing blood pressure (BP) in certain patients, but also in decreasing cardiac hypertrophy and arrhythmias. These pleiotropic effects occur partly independent from the observed BP reduction. Eleven patients with resistant hypertension (mean office systolic BP 180 ± 18 mmHg, mean antihypertensive medications 6.0 ± 1.5) underwent I-123-mIBG scintigraphy to exclude pheochromocytoma. We measured cardiac sympathetic innervation and activity before and 9 months after RDN. Cardiac sympathetic innervation was assessed by heart to mediastinum ratio (H/M) and sympathetic activity by wash out ratio (WOR). Effects on office BP, 24 h ambulatory BP monitoring, were documented. Office systolic BP and mean ambulatory systolic BP were significantly reduced from 180 to 141 mmHg (p = 0.006) and from 149 to 129 mmHg (p = 0.014), respectively. Cardiac innervation remained unchanged before and after RDN (H/M 2.5 ± 0.5 versus 2.6 ± 0.4, p = 0.285). Cardiac sympathetic activity was significantly reduced by 67 % (WOR decreased from 24.1 ± 12.7 to 7.9 ± 25.3 %, p = 0.047). Both, responders and non-responders experienced a reduction of cardiac sympathetic activity. RDN significantly reduced cardiac sympathetic activity thereby demonstrating a direct effect on the heart. These changes occurred independently from BP effects and provide a pathophysiological basis for studies, investigating the potential effect of RDN on arrhythmias and heart failure.

Short-term effects of catheter-based renal denervation on cardiac sympathetic drive and cardiac baroreflex function in heart failure

ObjectivesSympathetic drive, especially to the heart, is elevated in heart failure and is strongly associated with poor outcome. The mechanisms causing the increased sympathetic drive to the heart remain poorly understood. Catheter-based renal denervation (RDN), which reduces blood pressure (BP) and sympathetic drive in hypertensive patients, is a potential treatment in heart failure. The aim of this study was to investigate the short-term effects of catheter-based RDN on BP, heart rate (HR) and cardiac sympathetic nerve activity (CSNA) and on baroreflex function in a conscious, large animal model of heart failure. MethodsAdult Merino ewes were paced into heart failure (ejection fraction<40%) and then instrumented to directly record CSNA. The resting levels and baroreflex control of CSNA and HR were measured before and 24h after bilateral renal (n=6) or sham (n=6) denervation. RDN was performed using the Symplicity Flex Catheter System® (Medtronic) using the same algorithm as in patients. ResultsCatheter-based RDN significantly reduced resting diastolic BP (P<0.01) and mean arterial blood pressure (P<0.05), but did not change resting HR or CSNA compared with sham denervation. Renal denervation reduced the BP at which CSNA was at 50% of maximum (BP50; P<0.005) compared with sham denervation. ConclusionsIn an ovine model of heart failure, catheter-based RDN did not reduce resting CSNA in the short-term. There was, however, a lack of a reflex increase in CSNA in response to the fall in arterial pressure due to a leftward shift in the baroreflex control of CSNA, which may be due to denervation of renal efferent and/or afferent nerves.

Reinnervation following catheter-based radio-frequency renal denervation.

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 11months 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 11months 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 11months 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 1week postdenervation, but normal levels at 11months 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.

Reinnervation of renal afferent and efferent nerves at 5.5 and 11 months after catheter-based radiofrequency renal denervation in sheep.

Previous studies indicate that catheter-based renal denervation reduces blood pressure and renal norepinephrine spillover in human resistant hypertension. The effects of this procedure on afferent sensory and efferent sympathetic renal nerves, and the subsequent degree of reinnervation, have not been investigated. We therefore examined the level of functional and anatomic reinnervation at 5.5 and 11 months after renal denervation using the Symplicity Flex catheter. In normotensive anesthetized sheep (n=6), electric stimulation of intact renal nerves increased arterial pressure from 99±3 to 107±3 mm Hg (afferent response) and reduced renal blood flow from 198±16 to 85±20 mL/min (efferent response). In a further group (n=6), immediately after denervation, renal sympathetic nerve activity was absent and the responses to electric stimulation were abolished. At 11 months after denervation (n=5), renal sympathetic nerve activity and the responses to electric stimulation were at normal levels. Immunohistochemical staining for renal efferent (tyrosine hydroxylase) and renal afferent nerves (calcitonin gene-related peptide), as well as renal norepinephrine levels, was normal 11 months after denervation. Findings at 5.5 months after denervation were similar (n=5). In summary, catheter-based renal denervation effectively ablated the renal afferent and efferent nerves in normotensive sheep. By 11 months after denervation the functional afferent and efferent responses to electric stimulation were normal. Reinnervation at 11 months after denervation was supported by normal anatomic distribution of afferent and efferent renal nerves. In view of this evidence, the mechanisms underlying the prolonged hypotensive effect of catheter-based renal denervation in human resistant hypertension need to be reassessed.