Renal Denervation Group Research Articles

Effects of renal denervation on endogenous ouabain in spontaneously hypertensive rats.

To investigate the role of renal denervation (RDN) on endogenous ouabain (EO) secretion in spontaneously hypertensive rats (SHR). Sixteen 12-week-old male SHR were randomly separated into the renal denervation group (RDNX group) and sham operation group (sham group), and eight age-matched Wistar Kyoto rats (WKY) were served as control group. EO concentrations, the Na+- K+-ATPaseactivity, and the expression of Na+-K+-ATPase were assessed. EO levels in serum, kidneys and hypothalamus of sham group were higher than in RDNX group (p < 0.05). Renal Na+-K+-ATPase activity subjected to denervation surgery showed significantly reduction when compared with the sham groups (p < 0.05). A positive correlation existed between norepinephrine (NE) content and Na+-K+-ATPase activity in the kidney (r2 = 0.579). Renal Na+-K+-ATPase α1 subunit mRNA expression was down-regulated in the RDNX group compared with the sham group (P < 0.05), while renal Na+-K+-ATPase α1 subunit mRNA expression was no statistical significance between the groups (P = 0.63). Immunohistochemical analysis showed that there were significant differences in the renal expression of Na+-K+-ATPasebetween the three groups (P < 0.05). These experiments demonstrate that RDN exerted an anti-hypertensive effect with reduction of EO levels and Na+-K+-ATPase activity and Na+-K+-ATPase α1 subunit expression of kidney in SHR.

Renal denervation inhibits the renin–angiotensin–aldosterone system in spontaneously hypertensive rats

ABSTRACT This study was conducted to explore the effect of renal denervation (RDN) on the renin–angiotensin–aldosterone system (RAAS) in spontaneously hypertensive rats (SHRs). Our experimental rats were randomly divided into the RDN group conducted by painting 10% phenol on the bilateral renal nerves (RDNX), the shamoperation group simply painting with saline (Sham), and the normotension control group (WKY) following all the animal blood and tissues of kidney, hypothalamus, and adrenal gland collected and examined 2 weeks after RDN operation. We found that the aldosterone (ALD) levels in serum and tissues all decreased in the RDNX group compared with the Sham group (p < .05). Meantime, the expression of angiotensin II type1 receptor (AT1R) mRNA also exhibited significantly reduced by 2.22-fold in the RDNX group compared to the Sham group identical to the expression of AT1R protein in the renal cortex and outer stripe of the outer medulla (OSOM) subjected to denervation surgery, which manifested the lower ATIR protein expression than the Sham group (p < .05). Besides, the expression of angiotensin II (Ang II) protein in the cortex , OSOM, and inner stripe of the outer medulla were all attenuated by RDN in comparison with the Sham group (p < .05). RDN reduced intrarenal RAAS and circulating RAAS to lower blood pressure and repair renal function.

Pulmonary and Systemic Hemodynamics following Multielectrode Radiofrequency Catheter Renal Denervation in Acutely Induced Pulmonary Arterial Hypertension in Swine.

Objective We aimed to assess the effects of renal denervation (RDN) on systemic and pulmonary hemodynamics in a swine model of thromboxane A2- (TXA2-) induced pulmonary arterial hypertension (PAH). Methods The study protocol comprised two PAH inductions with a target mean pulmonary artery pressure (PAP) of 40 mmHg at baseline and following either the RDN or sham procedure. Ten Landrace pigs underwent the first PAH induction; then, nine animals were randomly allocated in 1 : 1 ratio to RDN or sham procedure; the second PAH induction was performed in eight animals (one animal died of pulmonary embolism during the first PAH induction, and one animal died after RDN). In the RDN group, ablation was performed in all available renal arteries, and balloon inflation within artery branches was performed in controls. An autopsy study of the renal arteries was performed. Results At baseline, the target mean PAP was achieved in all animals with 25.0 [20.1; 25.2] mcg of TXA2. The second PAH induction required the same mean TXA2 dose and infusion time. There was no statistically significant difference in the mean PAP at second PAH induction between the groups (39.0 ± 5.3 vs. 39.75 ± 0.5 mmHg, P > 0.05). In the RDN group, the second PAH induction resulted in a numerical but insignificant trend toward a decrease in the mean systemic blood pressure and systemic vascular resistance, when compared with the baseline induction (74 ± 18.7 vs. 90.25 ± 28.1 mmHg and 1995.3 ± 494.3 vs. 2433.7 ± 1176.7 dyn∗sec∗cm−5, P > 0.05, respectively). No difference in hemodynamic parameters was noted in the sham group between the first and second PAH induction. Autopsy demonstrated artery damage in both groups, but RDN resulted in more severe lesions. Conclusions According to our results, RDN does not result in significant acute pulmonary or systemic hemodynamic changes in the TXA2-induced PAH model. The potential chronic effects of RDN on PAH require further research.

The influence of inhibiting renal neural regeneration on the efficacy of renal denervation to chronic heart failure.

AimsSome studies support the occurrence of nerve regeneration in renal arteries after renal denervation (RDN). But it is unclear whether inhibiting reinnervation after RDN is beneficial to enhancing the effect of RDN on chronic heart failure (CHF).Methods and resultsChronic heart failure Sprague Dawley rats induced by transverse aortic constriction were administered with the analogue of Nogo‐B (Nogo group) or its antagonist (NEP group) respectively after RDN. Echocardiography, messenger RNA, and protein expression of calcitonin gene‐related peptide (CGRP) in renal artery and nerves surrounding renal artery were detected. Relative protein expression of CGRP was significantly decreased in the Nog group compared with the RDN group (0.64 ± 0.51 vs. 1.68 ± 1.07, P = 0.048). The number of nerves surrounding renal artery was higher in the NEP group than in the Nog group. Left ventricular end‐systolic volume and diameter (LVVs and LVDs) were greatly decreased, and left ventricular ejection fraction (LVEF) and fractional shortening (FS) increased significantly in the RDN, Nog and NEP groups when compared with the HF group (all P < 0.05). No significant differences were observed in left ventricular end‐diastolic volume and diameter; LVDs; LVVs; FS; LVEF; and the levels of plasma renin, noradrenaline, and N‐terminal pro‐B‐type natriuretic peptide among three groups: the RDN, Nog, and NEP groups.ConclusionsReinnervation of renal artery occurred in CHF rats after RDN, which had no effect on therapeutic role of RDN in CHF, and inhibiting this neural regeneration had no clinical significance and did not affect the efficacy of RDN to CHF.

Renal Denervation Mitigated Fecal Microbiota Aberrations in Rats with Chronic Heart Failure.

Background Changes in the composition and diversity of gut microbiota, which can be altered by autonomic nerve activity, contribute to the development of heart failure (HF). Renal denervation (RDN) can improve cardiac function by reducing sympathetic nerve activity. However, whether the beneficial role of RDN on HF is related to gut microbiota is unknown. Methods Thirty rats were assigned to a control, HF (with induced transverse aortic constriction (TAC)), RDN (with RDN induced 10 weeks after TAC), Nog (HF rats with Nogo-P4-administered 8 weeks after RDN), and NEP (HF rats with NEP1-40-administered 8 weeks after RDN) group. Then, 16SrRNA amplicon sequencing and analyses of fecal samples were performed. Results Beta diversity analyses revealed that compared to the HF group, the RDN, Nog, and NEP groups clustered closer to the control group. The Firmicutes/Bacteroidetes ratio was reduced in the HF group (1.59) compared with the control group (3.21) and was significantly decreased compared to the Nog (7.19), RDN (6.20), and NEP (4.42) groups. At the genus level, the HF group showed decreased abundances of Lactobacillus and Alistipes and increased abundances of Bacteroides and Clostridium compared with the control group. The abundances of Lactobacillus and Alistipes were increased, and those of Bacteroides and Clostridium were decreased in the RDN, Nog, and NEP groups compared to the HF group. However, no differences were observed between the three groups that underwent RDN. The microbial function showed the same tendency. Conclusions RDN reversed the abnormal changes in the gut microbiome in HF rats. Inhibition of reinnervation after RDN did not affect intestinal bacteria.

Catheter-based ultrasound renal denervation in patients with resistant hypertension: the randomized, controlled REQUIRE 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 registrationNCT02918305 (http://www.clinicaltrials.gov).

Sustained strong blood pressure lowering and preserved renal function during 3 year after anatomically optimized distal renal denervation according to the double blind randomized controlled study

Abstract Aim To evaluate long-term safety and efficacy of anatomically optimized distal renal denervation (RDN). Methods We assessed major adverse cardiovascular and renal events; changes in BP (office, ambulatory), and renal function (serum creatinine, eGFR) over 3 year follow-up extension of our double blind, randomized controlled study of the efficacy and safety of distal RDN versus conventional main trunk treatment in patients with true resistant hypertension (NCT02667912). Results Of 55 randomized patients (28/27, distal/main trunk RDN, respectively), 47 (23/24) were assessed at 1 year, and 39 (21/18) - at 3-year post-procedure. During 3-year follow-up 2 fatal and 2 non-fatal strokes were observed in distal RDN group versus one heart failure death and 2 non-fatal strokes in group of main trunk treatment. In distal RDN arm BP remained powerfully and significantly lowered both at 1 and 3 years post-procedure: −18.0 (95% CI −27.6; −8.5) and −16.9 (95% CI −27.3; −6.5) mmHg, 24h ambulatory systolic. During 1st year this potent BP lowering effect was accompanied by moderate eGFR decrease: −8.9 (95% CI −14.8; −3.1) ml/min/sq.m, however, this decrease was later reduced to non-significant −6.5 (95% CI −13.2; 0.3) ml/min/sq.m at 3 year post-procedure signaling some improvement in renal function after 1st year despite sustained strong BP lowering. In group of main trunk intervention BP only moderately decreased at 1 year −12.1 (95% CI −19.2; −5.0) mmHg, in parallel with small non-significant change in eGFR: −1.3 (95% CI −6.6; 4.0) ml/min/sq.m. Subsequently, BP lowering effect weakened and lost significance at 3 years post-procedure: −8.5 (95% CI −19.7; 2.2) mmHg. In contrast, eGFR continued to decline and reached significant −5.0 (95% CI −9.6; −0.3) ml/min/sq.m at the end of the study. Five patients developed new onset chronic kidney disease after main trunk RDN versus 3 patients – after distal RDN. The number of concomitant antihypertensive medications did not significantly changed in either group. Conclusion Our data demonstrate strong long-term BP lowering efficacy of distal RDN and, also, the potential of this procedure to prevent the decline of renal function in patients with resistant hypertension. Funding Acknowledgement Type of funding sources: None.

Renal denervation in hypertension patients: Proceedings from an expert consensus roundtable cosponsored by SCAI and NKF.

Renal denervation in hypertension patients: Proceedings from an expert consensus roundtable cosponsored by SCAI and NKF.

Role of Renin-Angiotensin System, Renal Nerve System, and Oxidative Stress in Chronic Stress-Induced Renal Expression of Aquaporin-1 in Rats

Aims: To investigate the renal aquaporin-1 (AQP1) expression under chronic stress (induced by foot shock) condition and possible mechanisms involved in rats. Methods: The chronic stress model was established in male Sprague Dawley (SD) rats by foot shock for two weeks. Rats were randomly divided into control group, chronic stress group, renal denervation group, renal denervation plus chronic stress group, captopril (an angiotensin I converting enzyme inhibitor, ACEI) plus chronic stress group and tempol (a superoxide dismutase mimetic) plus chronic stress group. Body weight, food intake, water intake, blood pressure and heart rate were monitored. Real-time PCR was used to detect the mRNA level of AQP1 in the renal tissue. Immunohistochemistry stain was used to observe the expression and location of AQP1 in rat kidneys. Results: Chronic stress reduced body weight gain and food intake, while it significantly increased systolic blood pressure and renal expressions of mRNA and protein of AQP1 (P&lt;0.05) as compared with control group. Renal denervation and tempol treatments did not affect stress-induced decreases of body weight gain and food intake. Renal denervation, captopril and tempol treatments decreased systolic blood pressure. Compared with the chronic stress group, mRNA and protein expression of AQP1 was decreased (P&lt;0.05) in renal denervation plus chronic stress group, captopril plus chronic stress group and tempol plus chronic stress group. Conclusion: Chronic stress induces increase of the AQP1 expression in kidney, which is regulated by renal nerve system, renin-angiotensin system and oxidative stress.

Ultrasound renal denervation for hypertension resistant to a triple medication pill (RADIANCE-HTN TRIO): a randomised, multicentre, single-blind, sham-controlled trial

Endovascular renal denervation reduces blood pressure in patients with mild-to-moderate hypertension, but its efficacy in patients with true resistant hypertension has not been shown. We aimed to assess the efficacy and safety of endovascular ultrasound renal denervation in patients with hypertension resistant to three or more antihypertensive medications. In a randomised, international, multicentre, single-blind, sham-controlled trial done at 28 tertiary centres in the USA and 25 in Europe, we included patients aged 18-75 years with office blood pressure of at least 140/90 mm Hg despite three or more antihypertensive medications including a diuretic. Eligible patients were switched to a once daily, fixed-dose, single-pill combination of a calcium channel blocker, an angiotensin receptor blocker, and a thiazide diuretic. After 4 weeks of standardised therapy, patients with daytime ambulatory blood pressure of at least 135/85 mm Hg were randomly assigned (1:1) by computer (stratified by centres) to ultrasound renal denervation or a sham procedure. Patients and outcome assessors were masked to randomisation. Addition of antihypertensive medications was allowed if specified blood pressure thresholds were exceeded. The primary endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Safety was also assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02649426. Between March 11, 2016, and March 13, 2020, 989 participants were enrolled and 136 were randomly assigned to renal denervation (n=69) or a sham procedure (n=67). Full adherence to the combination medications at 2 months among patients with urine samples was similar in both groups (42 [82%] of 51 in the renal denervation group vs 47 [82%] of 57 in the sham procedure group; p=0·99). Renal denervation reduced daytime ambulatory systolic blood pressure more than the sham procedure (-8·0 mm Hg [IQR -16·4 to 0·0] vs -3·0 mm Hg [-10·3 to 1·8]; median between-group difference -4·5 mm Hg [95% CI -8·5 to -0·3]; adjusted p=0·022); the median between-group difference was -5·8 mm Hg (95% CI -9·7 to -1·6; adjusted p=0·0051) among patients with complete ambulatory blood pressure data. There were no differences in safety outcomes between the two groups. Compared with a sham procedure, ultrasound renal denervation reduced blood pressure at 2 months in patients with hypertension resistant to a standardised triple combination pill. If the blood pressure lowering effect and safety of renal denervation are maintained in the long term, renal denervation might be an alternative to the addition of further antihypertensive medications in patients with resistant hypertension. ReCor Medical.

The impact of renal denervation treatment on left ventricular remodeling in patients with resistant hypertension

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Agency for Research an Development OnBehalf HIPERDIAB Background Increased blood pressure is considered the major determinant for structural alterations of the left ventricle resulting in increased myocardial mass and pathological remodeling. Renal denervation is a novel treatment for hypertensive patients with promising results on blood pressure levels. Purpose Evaluation of impact of renal denervation treatment on indices of left ventricular remodeling in patients with resistant hypertension. Methods 75 patients with resistant hypertension after a 3-week standardized treatment with Losartan 100 mg, Amlodipine 10 mg and Indapamid 1,5 mg were randomly assigned into three equal groups, depending on medication supplemented to previously administered: IM group - Moxonidine, IIB group - Bisoprolol and IIID group – renal artery denervation (RDN). Patients were assessed by echocardiographic exam at baseline and 6 months follow-up. Renal denervation was performed with a Symplicity Spyral catheter. Results Increased at the baseline in all three groups (170,96 ± 11,69 g/m2 in IM versus 156,5 ± 11,08 g/m2 in IIB and 164,94 ± 9,61 g/m2 in IIID groups) left ventricular mass index at 6 months of evaluation noted a statistically authentic reduction in all three groups, the group of patients treated with Moxonidine and RDN having a comparable and superior effect to the group treated with Bisoprolol (159,02 ± 10,34 g/m2 versus 150,5 ± 10,51 g/m2 and 149,15 ± 9,31 g/m2 in IM, IIB and IIID groups, p &amp;gt; 0,05). Simultaniously with the regression of left ventricular myocardial hypertrophy all three treatment regimens induced the improvement of its geometry, renal denervation group demonstrated a superior effect in ameliorating of this parameter (Tab.). Conclusion The data obtained confirmed the benefit of RDN treatment in patients with resistant hypertension in inducing reverse-remodeling of the LV, the beneficial effect being superior to both pharmacotherapeutic regimens. Geometric pattern of the left ventricle Group IM Group IIB Group IIID χ2 p baseline Concentric remodeling 5 (20%) 5 (20%) 4 (16%) 0,71 &amp;gt; 0,05 Concentric hypertrophy 13 (52%) 15 (60%) 14 (56%) Excentric hypertrophy 7 (28%) 5 (20%) 7 (28%) Normal geometry - - - 6 months Concentric remodeling 3 (12%) 7 (28%) 7 (28%) 4,61 &amp;lt; 0,05 Concentric hypertrophy 13 (52%) 13 (52%) 10 (40%) Excentric hypertrophy 8 (32%) 5 (20%) 5 (20%) Normal geometry 1 (4%) - 3 (12%)

Changes in Plasma Renin Activity After Renal Artery Sympathetic Denervation

BackgroundThe renin-angiotensin-aldosterone system plays a key role in blood pressure (BP) regulation and is the target of several antihypertensive medications. Renal denervation (RDN) is thought to interrupt the sympathetic-mediated neurohormonal pathway as part of its mechanism of action to reduce BP. ObjectivesThe purpose of this study was to evaluate plasma renin activity (PRA) and aldosterone before and after RDN and to assess whether these baseline neuroendocrine markers predict response to RDN. MethodsAnalyses were conducted in patients with confirmed absence of antihypertensive medication. Aldosterone and PRA levels were compared at baseline and 3 months post-procedure for RDN and sham control groups. Patients in the SPYRAL HTN-OFF MED Pivotal trial were separated into 2 groups, those with baseline PRA ≥0.65 ng/ml/h (n = 110) versus <0.65 ng/ml/h (n = 116). Follow-up treatment differences between RDN and sham control groups were adjusted for baseline values using multivariable linear regression models. ResultsBaseline PRA was similar between RDN and control groups (1.0 ± 1.1 ng/ml/h vs. 1.1 ± 1.1 ng/ml/h; p = 0.37). Change in PRA at 3 months from baseline was significantly greater for RDN compared with control subjects (−0.2 ± 1.0 ng/ml/h; p = 0.019 vs. 0.1 ± 0.9 ng/ml/h; p = 0.14), p = 0.001 for RDN versus control subjects, and similar differences were seen for aldosterone: RDN compared with control subjects (−1.2 ± 6.4 ng/dl; p = 0.04 vs. 0.4 ± 5.4 ng/dl; p = 0.40), p = 0.011. Treatment differences at 3 months in 24-h and office systolic blood pressure (SBP) for RDN versus control patients were significantly greater for patients with baseline PRA ≥0.65 ng/ml/h versus <0.65 ng/ml/h, despite similar baseline BP. Differences in office SBP changes according to baseline PRA were also observed earlier at 2 weeks post-RDN. ConclusionsPlasma renin activity and aldosterone levels for RDN patients were significantly reduced at 3 months when compared with baseline as well as when compared with sham control. Higher baseline PRA levels were associated with a significantly greater reduction in office and 24-h SBP. (SPYRAL PIVOTAL - SPYRAL HTN-OFF MED Study; NCT02439749)

The Effects of Renal Nerve Denervation on Blood Pressure and Target Organs in Different Hypertensive Rat Models.

Background Hypertension contributes to the progression of cardiac remodeling and renal damage. In turn, renal sympathetic hyperactivation showed elevated sympathetic nervous system activity and led to blood pressure increase in certain patients. The purpose of this study was to observe the effect of renal nerve denervation on blood pressure and target organ changes in two hypertensive rat models. Methods Hypertensive rats were randomly divided into a renal denervation (RDN) group and sham operation group. Wistar–Kyoto (WKY) rats of the same age were set as the baseline control group. In the secondary hypertension model, SD rats were randomly divided into five groups. Blood pressure and bodyweight were measured every week until they were euthanized. Results The two rat models underwent RDN at key timepoints. At these timepoints, the hearts and kidneys were collected for norepinephrine and angiotensin II measurements and histological analysis. Conclusion RDN performed before development of hypertension showed a significant antihypertensive effect on the secondary hypertension model.

NONINVASIVE 24-HOUR HEMODYNAMICS PREDICT BLOOD PRESSURE RESPONSE TO RENAL DENERVATION IN THE SPYRAL HTN-OFF MED PILOT AND PIVOTAL TRIALS

Objective: To investigate whether hemodynamic measures obtained during regular 24-hour blood pressure (BP) monitoring may predict BP response to renal denervation (RDN) using the SYMPLICITY SPYRAL renal denervation system. Design and method: This was a post-hoc analysis from the SPYRAL HTN-OFF MED pilot and pivotal trials. We used the raw BP waveforms, obtained at baseline and 3 months during 24-hour BP monitoring with an oscillometric sphygmomanometer. Waveforms were acquired at diastolic BP level, underwent in-device and post-hoc quality control, and were processed with validated ARCSolver algorithms to derive parameters of pulsatile hemodynamics (Augmentation Index – AIx). AIx quantifies the impact of wave reflection on the central aortic waveform. Its main hemodynamic determinants are aortic stiffness, peripheral resistance, heart rate and left ventricular function. We investigated the relationship between 24-hour AIx at baseline and the change in 24-hour systolic and diastolic BP (SBP/DBP) at 3 months in the combined RDN groups from both trials. Data were adjusted for observed trends in the sham group. We defined a favorable response as a drop in 24-hour systolic BP of at least 5 mm Hg. Results: Raw pressure waveforms were available for analysis in 103 patients undergoing RDN and 104 sham controls. Baseline characteristics and 24-hour BP changes at follow-up were comparable to the original trials. The relationship between baseline AIx and change in 24-hour SBP/DBP in the RDN group was: -8.2/-6.6 mm Hg for AIx &lt; = 50. percentile and -0.8/-0.8 mm Hg for AIx &gt; 50. percentile (p &lt; 0.001). In addition, a higher heart rate at baseline was associated with a larger BP drop at 3 months. Taking AIx and heart rate into account, a favorable BP response following RDN could be predicted with an area under the curve of 0.70. Interestingly, baseline BP was no longer associated with BP response to RDN after adjustments for the BP changes in the sham group. Conclusions: Our hypothesis-generating results for the first time suggest that hemodynamic measures, obtained during regular 24-hour BP monitoring in the workup before RDN, may predict BP response. Due to sample size, further investigation is needed.

BLOOD PRESSURE EFFECTS OVER TIME OF BIPOLAR RADIOFREQUENCY RENAL DENERVATION IN UNTREATED HYPERTENSION

Objective: It is believed that interruption of the renal nerves which lie in close proximity to the renal arteries, will effectively reduce blood pressure. As a first step, this study measured the blood pressure effects of ablating these nerves using radiofrequency energy produced by a bipolar catheter positioned into each renal artery in untreated hypertensive patients. Design and method: REINFORCE was a randomized, sham-controlled multicenter trial. Patients with office systolic blood pressure (SBP) of 150–180 mmHg and average 24-hour ambulatory SBP of 135–170 mmHg after medication washout underwent bipolar radiofrequency renal denervation or a sham procedure. The planned outcome was 8-week change in 24-hour ambulatory SBP. Enrollment was terminated for apparent futility before a sufficient sample for powered efficacy comparisons was enrolled, although patient observation continued. Safety assessments included all-cause death, renal failure, severe hypotension/syncope, hypertensive crisis, and renal artery stenosis. Results: Baseline 24-hour BP was 148.3 ± 10.9/85.7 ± 9.1 mmHg for the denervation group (N = 34, age 58.5 ± 10.1 years, 47% female) and 149.1 ± 7.2/86.4 ± 9.8 mmHg for the control group (N = 17, age 58.2 ± 9.8 years, 24% female). At 8 weeks, mean 24-hour SBP reductions for the renal denervation and control groups were 5.3 mmHg (95%CI -8.8, -1.8) and -8.5 mmHg (95%CI -13.3, -3.8), respectively (difference 3.3 [95%CI -2.8, 9.3]; p = .30). Antihypertensive medications could then be added. By 6 months, decreases in SBP were greater for the denervation group, yielding between-group differences of -7.2 (95%CI -15.2, 0.8; p = .08), -9.7 (95%CI -17.7, -1.7; p = .02), and -11.4 (95%CI -19.2, -3.7; p &lt; .01) for 24-hour, daytime ambulatory, and office measurements, respectively. Control rates (office SBP &lt; 140) were higher in the denervation group both at 6 months (52% vs. 12%, p &lt; 0.01) and 12 months (42% vs. 13%, p = 0.048). Medication use was similar in both groups. By 12 months, one denervation patient had a hypertensive urgency and one experienced progression of renal artery stenosis. Conclusions: The antihypertensive effects of renal denervation can be delayed for weeks following the procedure, but then appear to be sustained for at least 12 months.

IMPACT OF POLYPHARMACY AND COMORBIDITIES TO CLINICAL OUTCOMES IN RESISTANT HYPERTENSION RENAL DENERVATION GROUP

Objective: To analyse impact of polypharmacy to blood pressure control in resistant hypertension renal denervation group. Design and method: This prospective study included 73 selected patients with resistant hypertension and RDN (Sympathetic Renal Denervation) performed. Routine follow up was performed subsequently 1, 3, 6, 12, 24 and 48 months after the RDN. Total numbers of pills, prescibed for all diseases was registered. Two groups of patients were defined: A group- patient whom less than 7 pills prescribed and group B -more than 7 pills. Number of antihypertensive medications was analysed separately Also various characteristics were registered: age, sex, comorbidities, 24h-ABPM, arterial stiffness etc. Statistical analysis was performed using SPSS 23.0 Statistical Software. Results: A total cases of 73 patients were included. 6 patients died, 18 failed to remain in the follow up during 4 years. Remaining 49 patients data were analyzed. Median age was 55 (33–72) years old with 53,1 % (n = 26) patients being male. Two groups were similar, acoording to age, weight, office blood pressure, heart rate (p &gt; 0,05), but there was higher numbers of diabetes melitus and coronary artery disease in group B. Mean prescribed antihypertensive drugs (A- 4,75; B- 6,52; p &gt; 0,05). In A group we observed significantly reduced BP (sABP 162,6mmHg to 149,6mmHg, p &lt; 0,01; dABP 100,8mmHg to 90,24mmHg, p = 0,01) during 48 months. In B group: sABP 163,76 mmHg to 152,1mmHg, p = 0,13; dABP 89,7 mmHg to 85,1 mmHg, p = 0,54). In A group we observed significantly reduced carotid-femoral aortic pulse wave velocity (AoPWV) from 11.2 m/s to 10.0 m/s in 4 years (p = 0,01). In second group AoPWV increased from 11,8 m/s to 12,8 m/s, but not significantly (p = 0.34). Conclusions: Patients with more comorbidities and receiving more pills are at higher cardiovascular risk and their blood pressure is more difficult to control, even after renal denervation procedure.

Thirty-six-month results of laparoscopic-based renal denervation plus unilateral laparoscopic adrenalectomy for the treatment of patients with resistant hypertension caused by unilateral aldosterone-producing adenoma.

The aim of this study was to explore the long‐term clinical results of Renal denervation (RDN) from the adventitia of the renal artery plus unilateral laparoscopic adrenalectomy to treat patients with resistant hypertension caused by unilateral aldosterone‐producing adenoma (APA). Sixty patients with resistant hypertension caused by APA who were treated at Henan Provincial People's Hospital from December 2016 to March 2018 were selected and randomly assigned to undergo RDN from the adventitia of the renal artery plus adrenalectomy (RDN group, n = 30) or adrenalectomy alone (control group, n = 30). Office blood pressure (BP), antihypertensive medication usage and other laboratory characteristics were followed every 6 months through 36 months. Follow‐up data were available at 36 months for 23 of 30 subjects in the RDN group and for 21 of 30 subjects who were in the control group. At 36 months postprocedure, the reduction in the RDN group was 42.2 ± 21.6 mmHg and that in the control group was 29.8 ± 13.5 mmHg (p = .029 between the groups). During the follow‐up to 36 months postprocedure, no patients in either the RDN group or the control group died due to surgical complications, and the RDN group had no procedural complications, including renal artery dissection, perforation, and renal artery stenosis. There was no change in the mean eGFR of the two groups, and no serious adverse events were reported. In conclusion, RDN from the adventitia of the renal artery plus unilateral laparoscopic adrenalectomy resulted in sustained lowering of BP at 3 years in a selected population of subjects with resistant hypertension caused by unilateral APA without serious safety concerns.

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 ).

12-Month Results From the Unblinded Phase of the RADIANCE-HTN SOLO Trial of Ultrasound Renal Denervation.

This study reports the 12-month results of the RADIANCE-HTN (A Study of the ReCor Medical Paradise System in Clinical Hypertension) SOLO trial following unblinding of patients at 6months. The blood pressure (BP)-lowering efficacy and safety of endovascular ultrasound renal denervation (RDN) in the absence (2months) and presence (6months) of antihypertensive medications were previously reported. Patients with daytime ambulatory BP≥135/85mmHg after 4weeks off medication were randomized to RDN (n=74) or sham (n=72) and maintained off medication for 2months. A standardized medication escalation protocol was instituted between 2 and 5months (blinded phase). Between 6 and 12months (unblinded phase), patients received antihypertensive medications at physicians' discretion. Outcomes at 12months included medication burden, change in daytime ambulatory systolic BP (dASBP) and office or home systolic BP (SBP), visit-to-visit variability in SBP, and safety. Sixty-five of 74 RDN patients and 67 of 72 sham patients had 12-month dASBP measurements. The proportion of patients on≥2 medications (27.7% vs. 44.8%; p=0.041), the number of medications (0 vs. 1.4; p=0.015), and defined daily dose (1.4 vs. 2.2; p=0.007) were less with RDN versus sham. The decrease in dASBP from baseline in the RDN group (-16.5 ± 12.9mmHg) remained stable at 12months. The RDN versus sham adjusted difference at 12months was-2.3mmHg (95% confidence interval [CI]:-5.9 to 1.3mmHg; p=0.201) for dASBP,-6.3mmHg (95%CI:-11.1 to-1.5mmHg; p=0.010) for office SBP, and-3.4mmHg (95%CI:-6.9 to 0.1mmHg; p=0.062) for home SBP. Visit-to-visit variability in SBP was smaller in the RDN group. No renal artery injury was detected on computed tomographic or magnetic resonance angiography. Despite unblinding, the BP-lowering effect of RDN was maintained at 12months with fewer prescribed medications compared with sham.

Abstract 14713: Renal Denervation: Impact on Non-ST Segment Elevation Myocardial Infarction Rates in Patients With Hypertensive Heart Disease

Introduction: Catheter-based renal denervation (RDN) is an emerging therapy for hypertension, with potential ancillary benefits, e.g. a decrease in atrial fibrillation. Little is known about its effects on coronary artery disease (CAD) and acute coronary syndromes (ACS), e.g. non-ST segment elevation myocardial infarction (NSTEMI). Hypothesis: RDN reduces the incidence of NSTEMI in patients with hypertension and CAD. Methods: Data were retrospectively analyzed from the Renal Sympathetic Denervation Prevents Atrial Fibrillation in Patients with Hypertensive Heart Disease (RDPAF) trial (NCT01990911), which prospectively randomized individuals with uncontrolled hypertension and hypertensive heart disease to RDN or sham procedure groups in a 1:1 fashion. All patients required an indication for invasive coronary angiography. The impact of RDN on incident NSTEMI was evaluated with a log-rank test. Results: A total of 80 patients (mean age 65±8 years, 73% male) were analyzed: 42 (53%) patients underwent RDN, while 38 (47%) received sham-RDN. Baseline characteristics did not differ between groups: 54% of the total study population had diabetes mellitus, 88% took statins, 13% were current smokers and 68% had established CAD. After a mean follow-up of 38±23 months, 9 (11%) patients experienced a NSTEMI: 1 RDN (2.38%) vs 8 sham patients (21%) (OR: 0.092; 95% CI: 0.01 to 0.77; p=0.009; figure). Office systolic blood pressures decrease after six months’ follow-up did not differ between groups (-12.88mmHg in RDN vs. -9.13 mmHg in sham group; p= 0.49). Conclusions: Hypertensive patients who underwent RDN experienced a lower rate of NSTEMI during long term follow-up, compared to a sham-RDN control group. This may signal a novel benefit of RDN, i.e. a reduction in the incidence of ACS. Larger, prospective studies are needed to test this hypothesis and unravel potential protective mechanisms of RDN.