Renal Sympathetic Denervation Group Research Articles

Renal sympathetic denervation can significantly reduce blood pressure and improve arterial stiffness in hypertensive beagles

To investigate the effect of renal sympathetic denervation (RDN) on blood pressure and arterial stiffness in hypertensive beagles and explore the underlying mechanism. Sixteen beagles were randomly divided into RDN group (n=8, fed with a high-salt high-fat diet to establish models of hypertension and treated with RDN), sham-operated group (n=4, fed with a high-salt high-fat diet to induce hypertension but only examined with renal arteriography) and control group (n=4, fed with formula dog food). The changes in blood pressure, arterial stiffness, endothelial function, and sympathetic activity were compared among the 3 groups and correlation analysis was performed. All the animal models of hypertension were established successfully in the beagles. At 3 months after the RDN, the changes in systolic blood pressure (SBP) differed significantly among the 3 groups (P=0.006), and the reduction in SBP was significantly greater in RDN group than in the other two groups (P < 0.05). The variations of diastolic blood pressure (DBP) also differed significantly among the 3 groups (P=0.016), and DBP reduction was more obvious in RDN group than in the control group (P=0.007), but similar to that in the sham-operated group (P=0.052). The changes of resistance index (RI) after the procedure were significantly different among the 3 groups (P=0.043), and the RDN group showed a greater reduction of RI than the control group (P=0.032) and sham group (P=0.043). Serum levels of eNOS, NO and Ang Ⅱ did not differ significantly among the groups either before or after RDN (P>0.05), but serum NE level was significantly higher in RDN group than in the control groupafter successful modeling (P=0.014), but similar to that in the sham group (P=0.560). Compared with the sham operation, RDN in the hypertensive beagles resulted in a significantly greater decrease of serum NE level (P=0.032) to almost the control level (P= 0.080). The changes of RI following RDN were significantly correlated with the changes of SBP, DBP and serum levels of NO and NE (P < 0.05). RDN can significantly reduce blood pressure and improve arterial stiffness in hypertensive beagles possibly by reducing sympathetic activity and blood pressure and promoting NO synthesis.

Optimal Strategy for HIFU-Based Renal Sympathetic Denervation in Canines.

Background: The association between the treatment efficacy and safety of high-intensity focused ultrasound (HIFU)-based renal sympathetic denervation (RDN) and the acoustic energy dose applied has not been fully studied and may provide important understanding of the mechanism that led to failure of the WAVE IV trial. The objective of this study was to externally deliver different HIFU doses to canines for RDN treatment and to investigate the optimal energy dose for HIFU-based RDN.Methods: Thirty canines were divided into five RDN groups according to dose of acoustic energy applied, and a sham control group that consisted of four canines was used for comparisons. All animals in the RDN groups underwent the RDN procedure with different acoustic energy doses, while in the sham control group, renal arteries were harvested without being subjected to acoustic energy delivery and were imaged using color Doppler flow imaging (CDFI). Blood pressure (BP) was recorded, and blood samples were collected before the RDN procedure and at 28 days after the RDN procedure. Histological examinations and measurement of renal tissue norepinephrine concentration were performed in all retrieved samples.Results: Suppression of BP was significant in the 300 W (15.17/8.33 ± 1.47/1.21 mmHg), 250 W (14.67/9.33 ± 1.21/1.37 mmHg), and 200 W (13.17/9.17 ± 2.32/1.84 mmHg) groups. Semiquantitative histological assessment of periarterial nerves around the kidney revealed that target nerves in the 300 W (9.77 ± 0.63), 250 W (9.42 ± 0.67), and 200 W (9.58 ± 0.54) groups had the highest nerve injury scores, followed by the 150 W group (5.29 ± 0.62). Furthermore, decreased renal tissue norepinephrine concentration, together with decreased expression of tyrosine hydroxylase in the 300, 250, and 200 W groups demonstrated effective sympathetic depression following sufficient acoustic energy deposition. However, the renal artery injury score in the 300 W group (0.93 ± 0.13) was significantly higher than in the other groups (p < 0.001).Conclusion: This study provides evidence that RDN effectiveness is based on the energy dose delivered and that 200–250 W is effective and safe in normal-sized canines.

Endovascular renal sympathetic denervation to improve heart failure with reduced ejection fraction: the IMPROVE-HF-I study.

IntroductionThe aim of the present study was to assess the safety and efficacy of renal sympathetic denervation (RDN) in patients with heart failure with reduced ejection fraction (HFrEF).MethodsWe randomly assigned 50 patients with a left ventricular ejection fraction (LVEF) ≤ 35% and NYHA class ≥ II, in a 1:1 ratio, to either RDN and optimal medical therapy (OMT) or OMT alone. The primary safety endpoint was the occurrence of a combined endpoint of cardiovascular death, rehospitalisation for heart failure, and acute kidney injury at 6 months. The primary efficacy endpoint was the change in iodine-123 meta-iodobenzylguanidine (123I‑MIBG) heart-to-mediastinum ratio (HMR) at 6 months.ResultsMean age was 60 ± 9 years, 86% was male and mean LVEF was 33 ± 8%. At 6 months, the primary safety endpoint occurred in 8.3% vs 8.0% in the RDN and OMT groups, respectively (p = 0.97). At 6 months, the mean change in late HMR was −0.02 (95% CI: −0.08 to 0.12) in the RDN group, versus −0.02 (95% CI: −0.09 to 0.12) in the OMT group (p = 0.95) whereas the mean change in washout rate was 2.34 (95% CI: −6.35 to 1.67) in the RDN group versus −2.59 (95% CI: −1.61 to 6.79) in the OMT group (p-value 0.09).ConclusionRDN with the Vessix system in patients with HFrEF was safe, but did not result in significant changes in cardiac sympathetic nerve activity at 6 months as measured using 123I‑MIBG.Supplementary InformationThe online version of this article (10.1007/s12471-021-01633-z) contains supplementary material, which is available to authorized users.

Catheter-Based Radiofrequency Renal Sympathetic Denervation Decreases Left Ventricular Hypertrophy in Hypertensive Dogs.

This study explored the effects of renal sympathetic denervation (RDN) on hyperlipidity-induced cardiac hypertrophy in beagle dogs. Sixty beagles were randomly assigned to the control group, RDN group, or sham-operated group. The control group was fed with a basal diet, while the other two groups were given a high-fat diet to induce model hypertension. The RDN group underwent an RDN procedure, and the sham-operated group underwent only renal arteriography. At 1, 3, and 6 months after the RDN procedure, the diastolic blood pressure (DBP) and systolic blood pressure (SBP) levels were markedly decreased in the RDN group relative to the sham group (P < 0.05). After 6 months, serum norepinephrine (NE) and angiotensin II (AngII), as well as left ventricular levels, in the RDN group were statistically lower than those in the sham group (P < 0.05). Also, the left ventricular mass (LVM) and left ventricular mass index (LVMI) were significantly decreased, while the E/A peak ratio was drastically elevated (P < 0.05). Pathological examination showed that the degree of left ventricular hypertrophy and fibrosis in the RDN group was statistically decreased relative to those of the sham group and that the collagen volume fraction (CVF) and perivascular circumferential collagen area (PVCA) were also significantly reduced (P < 0.05). Renal sympathetic denervation not only effectively reduced blood pressure levels in hypertensive dogs but also reduced left ventricular hypertrophy and myocardial fibrosis and improved left ventricular diastolic function. The underlying mechanisms may involve a reduction of NE and AngII levels in the circulation and myocardial tissues, which would lead to the delayed occurrence of left ventricular remodeling.

Changes in sympathetic nervous system activity after renal denervation: results from the randomised Oslo RDN study

Purpose Sympathetic nervous system (SNS) over-activity is associated with essential hypertension. Renal sympathetic denervation (RDN) possibly lowers office- and ambulatory blood pressure (BP) in patients with treatment-resistant hypertension (TRH). We aimed to assess the effect of RDN compared to drug adjustment on SNS activity among patients with TRH by measuring plasma catecholamines and heart rate variability (HRV) during stress tests. Materials and methods Patients with TRH were randomised to RDN (n = 9) or Drug Adjustment (DA) (n = 10). We measured continuous HRV and beat-to-beat-BP using FinaPres® and obtained plasma catecholamines during standardised orthostatic- and cold-pressor stress tests (CPT) before- and six months after randomisation. Results CPT revealed no differences between groups at baseline in peak adrenaline concentration (69.3 pg/mL in the DA group vs. 70.0 pg/mL in the RDN group, p = 0.38) or adrenaline reactivity (Δ23.1 pg/mL in the DA group vs. Δ29.3 pg/mL in the RDN group, p = 0.40). After six months, adrenaline concentrations were statistically different between groups after one minute (66.9 pg/mL in the DA group vs. 55.3 pg/mL in the RDN group, p = 0.03), and six minutes (62.4 pg/mL in the DA group vs. 50.1 pg/mL in the RDN group, p = 0.03). There was a tendency of reduction in adrenaline reactivity after six months in the RDN group (Δ26.3 pg/mL at baseline vs. Δ12.8 pg/ml after six months, p = 0.08), while it increased in the DA group (Δ13.6 pg/mL at baseline vs. Δ19.9 pg/mL after six months, p = 0.53). We also found a difference in the Low Frequency band at baseline following the CPT (667µs2 in the DA group vs. 1628µs2 in the RDN group, p = 0.03) with a clear tendency of reduction in the RDN group to 743µs2 after six months (p = 0.07), compared to no change in the DA group (1052µs2, p = 0.39). Conclusion Our data suggest that RDN reduces SNS activity after six months. This finding warrants investigation in a larger study. Clinical Trial Number registered at www.clinicaltrials.gov: NCT01673516

Renal sympathetic denervation attenuates left ventricle hypertrophy in spontaneously hypertensive rats by suppressing the Raf/MEK/ERK signaling pathway

ABSTRACT Objective To explore the effect of renal sympathetic denervation (RSD) on left ventricle hypertrophy and the Raf/MEK/ERK signaling pathway in spontaneously hypertensive rats (SHRs). Methods SHRs were divided into SHR, SHR + Sham, SHR + RSD and SHR + U0126 groups, with WKY rats as the baseline controls. The blood pressure of rats was observed, while myocardial fibrosis was evaluated through Masson staining. Thereafter, real-time quantitative polymerase chain reaction (qRT-PCR) was carried out to determine the levels of myocardial-hypertrophy-related markers, and Western blotting was used to measure the activity of the Raf/MEK/ERK signaling pathway. Results In comparison with the WKY group, significant increases were observed in the systolic pressure and diastolic pressure of rats from the other four groups at different time points after surgery. In addition, rats in these groups had obvious increases in LVMI, renal NE and IVSd and decreases in LVEDd, LVEF and LVFS. In addition, the CVF of myocardial tissues was increased, with the upregulation of ANP, BNP and β-MHC and the downregulation of α-MHC. For the activity of the Raf/MEK/ERK signaling pathway, the levels of p-Raf/Raf, p-MEK/MEK and p-ERK1/2/ERK1/2 were all remarkably elevated (all P < .05). Further comparison with the SHR group showed that the above indexes in the rats were significantly improved in the RSD group and SHR + U0126 group (all P < .05). Conclusion RSD may decrease blood pressure, mitigate hypertension-induced left ventricle hypertrophy and improve cardiac function efficiently in SHRs via the suppression of the Raf/MEK/ERK signaling pathway.

The randomised Oslo study of renal denervation vs. Antihypertensive drug adjustments: efficacy and safety through 7 years of follow-up

Purpose The blood pressure (BP) lowering effect of renal sympathetic denervation (RDN) in treatment-resistant hypertension shows variation amongst the existing randomised studies. The long-term efficacy and safety of RDN require further investigation. For the first time, we report BP changes and safety up to 7 years after RDN, compared to drug adjustment in the randomised Oslo RDN study. Materials and methods Patients with treatment-resistant hypertension, defined as daytime systolic ambulatory BP ≥135 mmHg after witnessed intake of ≥3 antihypertensive drugs including a diuretic, were randomised to either RDN (n = 9) or drug adjustment (n = 10). The initial primary endpoint was the change in office BP after 6 months. The RDN group had their drugs adjusted after 1 year using the same principles as the Drug Adjustment group. Both groups returned for long-term follow-up after 3 and 7 years. Results The decrease in office BP and ambulatory BP (ABPM) after 6 months did not persist, but gradually increased in both groups. From 6 months to 7 years follow-up, mean daytime systolic ABPM increased from 142 ± 10 to 145 ± 15 mmHg in the RDN group, and from 133 ± 11 to 137 ± 13 mmHg in the Drug Adjustment group, with the difference between them decreasing. In a mixed factor model, a significantly different variance was found between the groups in daytime systolic ABPM (p = .04) and diastolic ABPM (p = .01) as well as office diastolic BP (p<.01), but not in office systolic BP (p = .18). At long-term follow-up we unveiled no anatomical- or functional renal impairment in either group. Conclusions BP changes up to 7 years show a tendency towards a smaller difference in BPs between the RDN and drug adjustment patients. Our data support RDN as a safe procedure, but it remains non-superior to intensive drug adjustment 7 years after the intervention.

Renal sympathetic denervation in addition to pulmonary vein isolation reduces the recurrence rate of atrial fibrillation: an updated meta-analysis of randomized control trials.

Atrial fibrillation (AF) is the most common arrhythmia worldwide. The sympathetic nervous system plays an important role in initiation and maintenance of AF. Recent studies have shown that renal sympathetic denervation (RSD) reduced AF recurrences after conventional pulmonary vein isolation (PVI). Studies that have evaluated the role of RSD as an adjuvant to PVI have included different patient populations, ablation strategies, and follow-up approaches. We performed a meta-analysis to assess the potential incremental impact of RSD to PVI. We searched the databases of MEDLINE and EMBASE from inception to January 2020. Included studies were randomized controlled trials (RCTs) that compared the recurrence rates of AF in patients who underwent PVI and RSD versus PVI alone. Data from each study were combined using the random effects model to calculate odds ratios (OR) and 95% confidence intervals (CIs). Three RCTs consisted of four different studies during 2014-2020 involving 451 AF patients (223 patients underwent PVI alone and 228 patients underwent PVI with RSD) were included in the meta-analysis. Compared with PVI alone, the PVI with RSD group had a significantly lower risk of AF recurrence (pooled OR = 0.63, 95%CI 0.50-0.80, p < 0.001, I2= 0.0%). There was no publication bias observed in funnel plot as well as no small-study effect observed in Egger's test. Our systematic review and meta-analysis demonstrated a significant reduction of AF recurrence in select hypertensive patients who underwent RSD in addition to PVI compared with PVI alone. Larger studies are needed to validate the benefits of this approach in other AF populations and across different ablation strategies.

Renal Sympathetic Denervation Improves Outcomes in a Canine Myocardial Infarction Model.

BackgroundMyocardial infarction (MI) is the main cause of heart failure (HF), and sympathetic nerve activity is associated with prognosis chronic heart failure. Renal sympathetic denervation (RDN) is noted for its powerful effect on the inhibition of sympathetic nerve activity. This study investigated the effect of RDN on heart failure in dogs after myocardial infarction.Material/MethodsThe experimental animals were randomized into 2 groups: the MI group (n=12) and the sham operation group (n=6). In the MI group we established an MI model by permanently ligating the left anterior descending branch. After 4 weeks, the MI dogs were randomly divided into 2 groups: the MI+RDN group (MI+renal sympathetic denervation, n=6) and the simple MI group (n=6). Animals in the MI+RDN group underwent both surgical and chemical renal denervation.ResultsCompared with sham operation group, left ventricular fraction shortening (LVFS) and left ventricular ejection fraction (LVEF) were significantly reduced in the simple MI group, while the reduction was partly reversed in the MI+RDN group. RDN reduced sympathetic nerve activity and release of B-type natriuretic peptide (BNP) and Angiotensin II (AngII) in the MI+ RDN group but not in the simple MI group.ConclusionsCanine renal sympathetic denervation prevents myocardial malignant remodeling by lowering the activity of the systemic sympathetic nerve and inhibiting renin-angiotensin-aldosterone system (RASS) activation, providing a new target and method for the treatment of heart failure.

Abstract 17096: The Efficacy of Renal Sympathetic Denervation in End-Stage Renal Disease Patients

The efficacy of renal sympathetic denervation in end-stage renal disease patients under hemodialysis Chan Joon Kim, Kiyuk Chang, Daewon Kim, Manwon Park, Jung Sun Cho, Sung-Ho Her Introduction: The end-stage renal disease (ESRD) patients who are under under renal replacement therapy, have often have uncontrolled, resistant hypertension. Renal sympathetic denervation (RDN) with radiofrequency ablation catheter has shown promising results in resistant hypertension. The purpose this pilot study is to assess the efficacy of RDN in resistant hypertension in ESRD patients. Method: Patients who are under renal hemodialysis and inter-dialytic SBP &gt; 160 mmHg despite of three or more antihypertensives were eligible for enrollment. 8 patients were allocated to either medical therapy group or RDN group by randomization. RDN was performed with Symplicity RDN catheter (Medtronic®).The primary outcome was change in SBP change in an inter-dialytic day in 3 months. The secondary outcome was change in DBP in 3 months, left ventricular mass index (LVMI). Results: The baseline SBP/DBP were 172.2 ± 9.5/ 88.7 ± 12.1 mmHg for the intervention group and 164.0 ± 6.9/84.7 ± 13.4 for medical group. Baseline ambulatory SBP was 164.8 ± 4.4 for the intervention group and 162 ± 8.4 mmHg for medical therapy group. The 3 month SBP/DBP were 155.5 ± 12.2/80.2 ± 7.7 for the intervention group and 167.5 ± 10.3/83.6 mmHg for medical therapy group. The mean change in SBP was 18.4 ± 4.5 mmHg for the intervention group and 2.8 mmHg ± 3.8 mmHg for the medical group ( p =0.03). The mean LVMI 194.3 ± 10.4 g/m2 for the intervention group and 187.4 ± 11.5 g/m2 for the medical therapy group. The mean change in LVMI was 41.4 ± 3.5 g/m2 for the intervention group and 1.1 g ± 4.4 g/m2 for the medical group ( p =0.03). Conclusion: This pilot study suggests that RDN may have therapeutic effect in resistant hypertension in ESRD patients and may have a role in regression in left ventricular hypertrophy.

LONG-TERM OUTCOME OF THE RANDOMIZED OSLO-RDN STUDY

Objective: The blood pressure (BP) lowering effect of renal sympathetic denervation (RDN) in treatment resistant hypertension (TRH) shows variation among the few randomized studies. The duration of antihypertensive effect and long-term effect and safety of RDN requires further follow-up. We aimed to report the office, ambulatory blood pressure changes as well as long-term safety at 3 years follow-up in our Oslo-RDN study.Design and method: Patients with apparent TRH (n = 65) were referred specifically for RDN and those with secondary and spurious hypertension (n = 26) were excluded. TRH was defined as office systolic BP > 140 mmHg despite maximally tolerated doses of at least 3 antihypertensive drugs including a diuretic. Furthermore, ambulatory daytime systolic BP > 135 mmHg following witnessed intake of antihypertensive drugs was required. This procedure revealed that 20 patients had normalized BP, indicating poor adherence, and these patients were excluded. Patients with true TRH were randomized and underwent RDN with Symplicity catheter (n = 9) versus adjusted drug treatment (n = 10). Patients came for follow-up 3–4 years after baseline. Results: 24-hour ambulatory systolic and diastolic BPs in the drug adjustment group changed from 151 ± 13/84 ± 7 mmHg at baseline to 132 ± 15/77 ± 6 mmHg at 3-years, and in the RDN group from 149 ± 9/89 ± 7 mmHg at baseline to 137 ± 13/81 ± 10 mmHg at 3-years follow-up. Office, daytime and nighttime ambulatory BPs changed in parallel to the 24-hour ambulatory BPs. The absolute differences in systolic or diastolic BPs between the groups were consistent with earlier follow up points with a tendency toward a smaller difference between the groups. The difference in systolic BP at long-term follow up was not significant (p = 0.34). There were no significant changes in renal arteries assessed by MRI or CT scans at long-term follow-up. No deterioration of renal function was observed. Conclusions: The results at the three-year follow-up are consistent with earlier time points, with a tendency toward a smaller difference in BPs between the TRH and RDN groups. Our data support that RDN is a safe procedure on long-term follow-up and this allows further research to identify characteristics of patients who might respond to RDN.

Effect of renal sympathetic denervation on ventricular and neural remodeling.

BackgroundThis 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.MethodsWe 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.ResultsLeft 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.ConclusionRDN 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.

Catheter-based renal sympathetic denervation induces acute renal inflammation through activation of caspase-1 and NLRP3 inflammasome.

Objective:Catheter-based renal sympathetic denervation (RDN) is implemented as a strategy to treat resistant hypertension. Serum creatinine and estimated glomerular filtration rate have some limitations to predict the early stage of acute kidney injury (AKI). We investigated the changes of early inflammatory biomarkers in AKI following the RDN procedure.Methods:Twenty-five female swine were divided into three groups: normal control (Normal, n=5), sham-operated (Sham, n=5), and RDN groups (RDN, n=15). The RDN group was further subdivided into three subgroups according to the time of sacrifice: immediately (RDN-0, n=5), 1 week (RDN-1, n=5), and 2 weeks (RDN-2, n=5) after RDN. Renal cortical tissue was harvested, and clinical parameters and inflammatory biomarkers were checked.Results:There were no significant changes in the clinical parameters between the normal control and sham-operated groups using contrast media. Inflammatory interleukin (IL)-1β, IL-18, IL-6, tumor necrosis factor-α, and anti-inflammatory IL-10 increased immediately and then decreased at week 2 after RDN in the renal cortical tissue. Leaderless protein, IL-1α level, increased at week 1 and then decreased at week 2 after RDN. Caspase-1 increased immediately after RDN until week 2. Apoptosis-associated speck-like protein containing a caspase recruitment domain and NLRP3 expressions increased immediately and then decreased at week 2 after RDN.Conclusion:The RDN could induce acute renal inflammation through the activation of caspase-1 and NLRP3 inflammasome.

Pulmonary vein isolation combined with spironolactone or renal sympathetic denervation in patients with chronic kidney disease, uncontrolled hypertension, paroxysmal atrial fibrillation, and a pacemaker.

Atrial fibrillation (AF) commonly occurs in chronic kidney disease (CKD), occasioning adverse outcomes. Merging pulmonary vein isolation (PVI) and renal sympathetic denervation (RSD) may decrease the recurrence of AF in subjects with CKD and uncontrolled hypertension. We considered that RSD could reduce the recurrence of AF in patients with CKD by modulating sympathetic hyperactivity. We aimed to evaluate the impact of RSD or spironolactone 50mg/day associated with PVI in reducing systolic blood pressure (BP), AF recurrence, and AF burden in patients with a history of paroxysmal AF and mild CKD. This was a single-center, prospective, longitudinal, randomized, double-blind study. The individuals were randomly divided into two groups (PVI + spironolactone, n = 36, and PVI + RSD, n = 33). All of them were followed for exactly 1year to assess maintenance of sinus rhythm and to monitor the other variables. Ambulatory BP measurements were reduced in both groups and at the 12th month also differed between groups. Significantly more patients in the PVI + RSD (61%) than in the PVI + spironolactone group (36%) were AF-free at the 12th month of follow-up, P = 0.0242. Toward the end of the study, the mean AF burden was lower in the PVI + RSD group as compared to PVI + spironolactone group, at the 9th month: ∆ = - 10% (P < 0.0001), and at the 12th month: ∆ = - 12% (P < 0.0001), respectively. PVI + RSD is safe and appears to be superior to PVI + spironolactone in BP reduction, augmentation of AF event-free rate, reduction of AF burden, and improvement of renal function.

Renal simplicity denervation reduces blood pressure and renal injuries in an obesity-induced hypertension dog model.

This study aimed to investigate the effects of renal sympathetic denervation (RDN) on blood pressure, renal function, and renal tissue pathological changes in obesity-induced hypertensive dogs. Thirty-two beagle dogs (10-12months) were randomized to the control (n=10) and model groups (n=22). High-fat diet (HFD) was used to establish the obesity-induced hypertensive model. After 3months of HFD, 20 animals with successfully induced hypertension were randomized to the RDN (n=10) and sham groups (n=10). Renal artery angiography, body weight, blood pressure, heart rate (HR), and blood and urine biochemistry were determined 1, 3 and 6months after surgery. Models were killed 6months after surgery. Pathological changes in the renal artery and renal tissue were assessed. The HFD group had significantly (P<.05) increased body weight, HR, and blood pressure, and higher levels of urine albumin, serum noradrenaline, and angiotensin II compared with controls. After RDN, blood pressure was decreased compared with baseline and the sham group (P<.05). In the RDN group, examination of the renal artery and renal tissue showed intact intima of renal artery in the surgical area, renal sympathetic nerve degeneration, necrosis, and dissolution, and widened space between nerve fibres. Hypertension-induced renal pathological changes were mild to moderate in the RDN group, but severe in the sham group. The control group had normal glomerular structure. In conclusion, RDN can effectively lower blood pressure in obesity-induced hypertensive dogs, as well as hypertension-induced renal pathological changes.

Renal sympathetic denervation alleviates myocardial fibrosis following isoproterenol-induced heart failure.

The aim of the present study was to determine if renal sympathetic denervation (RSD) may alleviate isoproterenol-induced left ventricle remodeling, and to identify the underlying mechanism. A total of 70 rats were randomly divided into control (n=15), sham operation (n=15), heart failure (HF) with sham operation (HF + sham; n=20) and HF with treatment (HF + RSD; n=20) groups. The HF model was established by subcutaneous injection of isoproterenol; six weeks later, 1eft ventricular internal diameter at end-systole (LVIDs), left ventricular systolic posterior wall thickness (LVPWs), 1eft ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were measured. Plasma norepinephrine (NE), angiotensin II (Ang II) and aldosterone (ALD) levels were measured by ELISA. Myocardial collagen volume fraction (CVF) was determined by Masson's staining. Reverse transcription-quantitative polymerase chain reaction was used to determine the mRNA expression levels of ventricular transforming growth factor-β (TGF-β), connective tissue growth factor (CTGF) and microRNAs (miRs), including miR-29b, miR-30c and miR-133a. The results demonstrated that LVIDs and LVPWs in the HF + RSD group were significantly decreased compared with the HF + sham group. By contrast, LVFS and LVEF in the HF + RSD group were significantly increased compared with the HF + sham group. RSD significantly reduced the levels of plasma NE, Ang II and ALD. CVF in the HF + RSD group was reduced by 38.1% compared with the HF + sham group. Expression levels of TGF-β and CTGF were decreased, whereas those of miR-29b, miR-30c and miR-133a were increased, in the HF + RSD group compared with the HF + sham group. These results indicated that RSD alleviates isoproterenol-induced left ventricle remodeling potentially via downregulation of TGF-β/CTGF and upregulation of miR-29b, miR-30c and miR-133a. RSD may therefore be an effective non-drug therapy for the treatment of heart failure.

Evaluation of left ventricular systolic function after renal sympathetic denervation in beagles with heart failure by layer-specific two-dimensional speckle tracking imaging

Objective To assess the left ventricular systolic function after renal sympathetic denervation(RSD) in beagles with heart failure by layer-specific two-dimensional speckle tracking imaging. Methods Twenty-three beagles were randomly divided into control group (8 dogs), URSD group (8 dogs) and RSD group (7 dogs). Control group was implanted with pacemakers without pacing, URSD group was implanted with pacemakers and underwent 3 weeks of rapid right ventricular pacing, and RSD group underwent catheter-based RSD bilaterally and was simultaneously implanted with pacemakers. All standard measurements were obtained from the left ventricular short-axis views at the levels of mitral annulus, papillary muscle and apex, and apical four-chamber, two-chamber, and long-axis views. The peak systolic longitudinal strain and circumferential strain of each layer of the left ventricle were measured by layer-specific two-dimensional speckle tracking imaging. Results After 3 weeks, all of the dogs in both the URSD and RSD groups showed lower left ventricular diastolic and systolic function compared with those in the control group, however, the dogs in the RSD group had a higher LV ejection fraction (LVEF) than the dogs in the URSD group(P<0.05). Compared with the control group, the global longitudinal strain, circumferential strain and radial strain all decreased significantly in URSD and RSD groups. The longitudinal strain of endo- and mid-cardium and the circumferential strain in endo-cardium were significantly higher in RSD group than those in URSD group(P<0.05). Conclusions Myocardial systolic function is impaired in dogs with heart failure, layer-specific two-dimensional speckle tracking imaging can provide effective tools to assess the left ventricular systolic function. Renal sympathetic denervation can improve the myocardial systolic function in dogs with heart failure. Key words: Echocardiography; Renal sympathetic nerve; Catheter ablation; Ventricular function, left; Layer-specific speckle tracking imaging

Pharmacological Monotherapy versus Renal Artery Denervation in Controlled Hypertensive Patients

&lt;p&gt;&lt;strong&gt;Aim: &lt;/strong&gt;The aim of this prospective observational non-inferiority study was to compare the capacity for control of essential hypertension between renal sympathetic denervation (RSD) and either angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and results&lt;/strong&gt;: Seventy-four previously controlled essential hypertensive patients on ACEI/ARB monotherapy were evaluated; eleven patients agreed to proceed with RSD and had their antihypertensive agent withdrawn on the day of the procedure. During the six months of follow-up, there was no significant change in mean 24-hour ambulatory blood pressure measurements (ABPM) from baseline to three and sixmonths in the ACEI/ARB group (118±8/80±3 &lt;em&gt;vs.&lt;/em&gt; 116±8/79±3 and 115±8/79±4 mmHg, respectively). No change was also observed in the RSD group (117±8/81±2 &lt;em&gt;vs.&lt;/em&gt; 115±6/80±2 and 114±7/79±3 mmHg, respectively). There were no differences between groups at interval time points. There were also no changes in renal function or echocardiographic parameters, during follow-up.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; For the first time, this study reports possible non-inferiority of RSD when compared to ACEI or ARB monotherapy in the control of essential hypertension. A randomized trial with appropriate concealment of treatment, more patients and an extended follow-up period is needed to evaluate the potential benefits of RSD in comparison to ACEI/ARB use in patients with controlled hypertension.&lt;/p&gt;

Pulmonary vein isolation alone and combined with renal sympathetic denervation in chronic kidney disease patients with refractory atrial fibrillation

BackgroundAtrial fibrillation (AF) commonly occurs in association with chronic kidney disease (CKD), resulting in adverse outcomes. Combining pulmonary vein isolation (PVI) and renal sympathetic denervation (RSD) may reduce the recurrence of AF in patients with CKD and hypertension. We considered that RSD could reduce the recurrence of AF in patients with CKD by modulating sympathetic hyperactivity. Our goal was to compare the impact of PVI + RSD with that of PVI alone in patients with concurrent AF and CKD. MethodsThis was a single-center, prospective, longitudinal, randomized, double-blind study. Forty-five patients with controlled hypertension, symptomatic paroxysmal AF and/or persistent AF, stage 2 or 3 CKD, and a dual-chamber pacemaker were enrolled from January 2014 to January 2015. We assessed the 30-second recurrence of AF recorded by the pacemaker, 24-hour ambulatory blood pressure measurements, estimated glomerular filtration rate, albuminuria, echocardiographic parameters, and safety of RSD. ResultsNo patient developed procedural or other complications. The ambulatory blood pressure measurements did not differ within the PVI + RSD group or between the PVI + RSD and PVI groups throughout the study. Significantly more patients in the PVI + RSD group than in the PVI group were free of AF at the 12-month follow-up evaluation. The PVI group had an unacceptable response to ablation with respect to changes in echocardiographic parameters, whereas these parameters improved in the PVI + RSD group. ConclusionPVI + RSD were associated with a lower AF recurrence rate than PVI alone; it also improved renal function and some echocardiographic parameters. These encouraging data will serve as baseline information for further long-term studies on larger patient populations.

PS 11-83 ONE-YEAR OUTCOMES OF THE RANDOMIZED OSLO-RDN STUDY

Objective: The blood pressure (BP) lowering effect of renal sympathetic denervation (RDN) in treatment resistant hypertension (TRH) shows variation among the few randomized studies. The duration of antihypertensive effect and long-term effect and safety of RDN require further follow-up. We aimed to report the office and ambulatory (BP) changes and long-term safety at 12-month follow-up. Design and Method: Patients with apparent TRH (n = 65) were referred specifically for RDN and those with secondary and spurious hypertension (n = 26) were excluded. TRH was defined as office systolic BP>140 mmHg despite maximally tolerated doses of at least 3 antihypertensive drugs including a diuretic. Additionally, ambulatory daytime systolic BP > 135 mmHg following witnessed intake of antihypertensive drugs was required, after which 20 patients had normalized BP, indicating poor drug adherence. Patients with true TRH were randomized and underwent RDN with Symplicity catheter (n = 9) versus adjusted drug treatment (n = 10). Results: 24-hour ambulatory systolic and diastolic BPs in the drug adjustment group changed from 151 ± 13/84 ± 7 mmHg (±SD) at baseline to 131 ± 12/75 ± 5 mmHg at 12 months (p < 0.0005 for all), and in the RDN group from 149 ± 9/89 ± 7 to 141 ± 11/83 ± 5 mmHg (p = 0.07 and p = 0.04, respectively). The absolute difference in change between groups in systolic BP was significantly higher in favor of the drug adjustment group (p = 0.01). Office, daytime and nighttime ambulatory BPs changed in parallel to the 24-hour ambulatory BPs. However 2 patients in RDN group considered as a responder since they have sustained reduction of 24-hour ambulatory systolic BP by more than 15 mmHg. There were no significant changes in renal arteries assessed by MRI or CT scans after 12 months follow-up. No deterioration of renal function was found. Conclusions: RDN has inferior BP lowering effects compared to adjusted drug treatment in patients with TRH. However, RDN is safe and this encourages future research to identify characteristics of patients who might respond to RDN.