Catheter-based Renal Denervation Research Articles

Blunted natriuretic response to saline loading in sheep with hypertensive kidney disease following radiofrequency catheter-based renal denervation

Renal sympathetic nerves contribute to renal excretory function during volume expansion. We hypothesized that intact renal innervation is required for excretion of a fluid/electrolyte load in hypertensive chronic kidney disease (CKD) and normotensive healthy settings. Blood pressure, kidney hemodynamic and excretory response to 180 min of isotonic saline loading (0.13 ml/kg/min) were examined in female normotensive (control) and hypertensive CKD sheep at 2 and 11 months after sham (control-intact, CKD-intact) or radiofrequency catheter-based RDN (control-RDN, CKD-RDN) procedure. Basal blood pressure was ~ 7 to 9 mmHg lower at 2, and 11 months in CKD-RDN compared with CKD-intact sheep. Saline loading did not alter glomerular filtration rate in any group. At 2 months, in response to saline loading, total urine and sodium excretion were ~ 40 to 50% less, in control-RDN and CKD-RDN than intact groups. At 11 months, the natriuretic and diuretic response to saline loading were similar between control-intact, control-RDN and CKD-intact groups but sodium excretion was ~ 42% less in CKD-RDN compared with CKD-intact at this time-point. These findings indicate that chronic withdrawal of basal renal sympathetic activity impairs fluid/electrolyte excretion during volume expansion. Clinically, a reduced ability to excrete a saline load following RDN may contribute to disturbances in body fluid balance in hypertensive CKD.

Catheter-based alcohol-mediated renal denervation for the treatment of uncontrolled hypertension: design of two sham-controlled, randomized, blinded trials in the absence (TARGET BP OFF-MED) and presence (TARGET BP I) of antihypertensive medications

Arterial hypertension is a common and life-threatening condition and poses a large global health burden. Device-based treatments have been developed as adjunctive or alternative therapy, to be used with or without antihypertensive medication for treating uncontrolled hypertension. The safety and feasibility of chemical renal denervation (RDN) using the Peregrine Catheter and alcohol were demonstrated in a first-in-man and open-label clinical trials, prompting the initiation of the ongoing TARGET BP OFF-MED and TARGET BP I trials. The TARGET BP trials are randomized, blinded, sham-controlled trials designed to assess the safety and efficacy of alcohol-mediated RDN for the treatment of uncontrolled hypertension in the absence of antihypertensive medications (TARGET BP OFF-MED) or in addition to prescribed antihypertensive medications (TARGET BP I). Subjects with confirmed uncontrolled hypertension and suitable renal artery anatomy are randomized (1:1) to receive either RDN using the Peregrine Kit with alcohol (0.6mL per renal artery) infused through the Peregrine Catheter or diagnostic renal angiography only (sham procedure). TARGET BP OFF-MED completed enrollment and randomized 96 subjects. TARGET BP I will randomize approximately 300 subjects and will transition to an open-label safety cohort of approximately 300 subjects receiving RDN once the primary efficacy endpoint of the Randomized Controlled Trial (RCT) cohort has been met. Primary endpoints are change in mean 24-hour ambulatory systolic blood pressure from baseline to 8 weeks (TARGET BP OFF-MED) and 3months (TARGET BP I) post-procedure. The TARGET BP trials are the first large-scale, international, randomized trials aimed to investigate the safety and BP lowering efficacy of a novel RDN method, with perivascular alcohol delivery using the Peregrine Kit.

Ultrasound Renal Denervation Shows Modest Effects in Resistant Hypertension

Catheter-based renal denervation (RDN) has had mixed results in patients with hypertension. Recently, however, radiofrequency or ultrasound RDN has

Blood pressure and renal denervation with ultrasound: another step forward

Among cardiovascular risk factors, arterial hypertension has the highest prevalence and is poorly controlled. 1 Stanaway JD Afshin A Gakidou E et al. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018; 392: 1923-1994 Summary Full Text Full Text PDF PubMed Scopus (1438) Google Scholar The sympathetic nervous system targeting the kidney via efferent and afferent nerves, thereby contributing to hypertension and potentially other cardiovascular conditions, 2 Böhm M Linz D Ukena C Esler M Mahfoud F Renal denervation for the treatment of cardiovascular high risk-hypertension or beyond?. Circ Res. 2014; 115: 400-409 Crossref PubMed Scopus (62) Google Scholar can be modulated with different denervation technologies. 3 Lauder L Azizi M Kirtane AJ Böhm M Mahfoud F Device-based therapies for arterial hypertension. Nat Rev Cardiol. 2020; 17: 614-628 Crossref PubMed Scopus (17) Google Scholar Rigorously controlled clinical trials without 4 Böhm M Townsend RR Kario K et al. Rationale and design of two randomized sham-controlled trials of catheter-based renal denervation in subjects with uncontrolled hypertension in the absence (SPYRAL HTN-OFF MED Pivotal) and presence (SPYRAL HTN-ON MED Expansion) of antihypertensive medications: a novel approach using Bayesian design. Clin Res Cardiol. 2020; 109: 289-302 PubMed Google Scholar , 5 Böhm M Kario K Kandzari DE et al. Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial. Lancet. 2020; 395: 1444-1451 Summary Full Text Full Text PDF PubMed Scopus (102) Google Scholar , 6 Townsend RR Mahfoud F Kandzari DE et al. Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial. Lancet. 2017; 390: 2160-2170 Summary Full Text Full Text PDF PubMed Scopus (374) Google Scholar and with 7 Kandzari DE Böhm M Mahfoud F et al. Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the SPYRAL HTN-ON MED proof-of-concept randomised trial. Lancet. 2018; 391: 2346-2355 Summary Full Text Full Text PDF PubMed Scopus (302) Google Scholar antihypertensive medications have shown a significant reduction in blood pressure with high-frequency energy. Ultrasound renal denervation for hypertension resistant to a triple medication pill (RADIANCE-HTN TRIO): a randomised, multicentre, single-blind, sham-controlled trialCompared 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. Full-Text PDF

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.

ANATOMY OF RENAL DENERVATION DURABILITY

Objective: Safety and efficacy of catheter-based renal denervation (RDN) have been demonstrated in previous randomized, sham-controlled trials. Ongoing registries also suggest long-term durability of the RDN procedure. However, the exact mechanisms for RDN durability have not been previously elucidated. This report aimed to characterize the pathophysiological processes post radiofrequency (RF) RDN that translate into procedural durability utilizing animal models. Design and method: Animal studies were conducted in accordance with published guidelines. RDN was performed using the Symplicity RDN system (Medtronic, Santa Rosa, CA, USA) and the multielectrode RF Symplicity Spyral catheter in 164 healthy swine. Serial histological tissue samples were obtained 7, 28, 60, and 180 days post-procedure and followed by immunohistochemical and histopathologic analysis of RF-treated regions, sympathetic nerves and renal cortical axons. Results: At 7 days post-RDN, inflammation and swelling predominated the nerve lesions at the treatment site. A progressive nerve deterioration accompanied by Schwann cell reaction occurred over time leading to terminal atrophy and fibrosis at 180 days post-RDN. Nerve atrophy also became present distal to the treatment site. Although new Schwann cells appeared post-RDN, they failed to form the characteristic nerve fascicles and bundles which would reconstitute normal nerve morphology and support functional axons. Quantitative comparison of nerve necrosis and nerve atrophy indicated that proximal nerve necrosis peaks in the treated segments of the vessel, whereas nerve atrophy and low-grade nerve inflammation originates at the region of peak necrosis and extends distally beyond the RDN lesion. Thus, despite anatomic Schwann cell regeneration, the functional axonal nerve component did not recover. Conclusions: Histological analyses of porcine tissues demonstrated that terminal atrophy and fibrosis of the renal nerves developed within 180 days post-RF RDN procedure. Although new Schwan cell formation occurred, it did not reconstitute native nerve morphology suggesting functional nerve recovery is unlikely.

Laparoscopic Ablation System for Complete Circumferential Renal Sympathetic Denervation.

The catheter-based renal denervation (RDN) showed promising results for patients in lowering BP, but there were also many non-responders. One of the possible reasons was the incomplete neural ablation due to the ablation of renal nerves at random sites resulting in asymmetric innervation patterns along the renal artery. We developed a laparoscopic ablation system that is optimized for complete RDN regardless of renal arterial innervation and size. To demonstrate its effectiveness, we evaluated the system using computational simulation and 28-day survival model using pigs. The ablations were focused around the tunica externa, and the ablation patterns could be predicted numerically during RDN treatment. In the animal study, the mean reduction of systolic BP and diastolic BP in the bilateral main renal arteries was 22.8 mmHg and 14.4 mmHg (P<0.001), respectively. The respond to immunostaining targeting tyrosine hydroxylase was significantly reduced at treatment site (108.2 ± 7.5 (control) vs. 63.4 ± 8.7 (treatment), P<0.001), and an increased degree of sympathetic signals interruption to kidneys was associated with the efficacy of RDN. The laparoscopic ablation system achieved complete circumferential RDN at the treatment site and could numerically predict the ablation patterns. These findings clearly suggest that the proposed system can significantly improve the RDN effectiveness by reducing the variation to the percentage of injured nerves and open up a new opportunity to treat uncontrolled hypertension.

Role of the sympathetic nervous system in cardiometabolic control: implications for targeted multiorgan neuromodulation approaches.

Sympathetic overdrive plays a key role in the perturbation of cardiometabolic homeostasis. Diet-induced and exercise-induced weight loss remains a key strategy to combat metabolic disorders, but is often difficult to achieve. Current pharmacological approaches result in variable responses in different patient cohorts and long-term efficacy may be limited by medication intolerance and nonadherence. A clinical need exists for complementary therapies to curb the burden of cardiometabolic diseases. One such approach may include interventional sympathetic neuromodulation of organs relevant to cardiometabolic control. The experience from catheter-based renal denervation studies clearly demonstrates the feasibility, safety and efficacy of such an approach. In analogy, denervation of the common hepatic artery is now feasible in humans and may prove to be similarly useful in modulating sympathetic overdrive directed towards the liver, pancreas and duodenum. Such a targeted multiorgan neuromodulation strategy may beneficially influence multiple aspects of the cardiometabolic disease continuum offering a holistic approach.

Arterielle Hypertonie – Was war 2020 wichtig?

Die arterielle Hypertonie bleibt weltweit der prävalenteste Risikofaktor für kardiovaskuläre Erkrankungen und damit einhergehende Behinderungen. Auch im Bereich der arteriellen Hypertonie bestimmte die COVID-19-Pandemie einen Teil der wissenschaftlichen Debatte. Die arterielle Hypertonie ist mit einem schwereren Krankheitsverlauf von COVID-19 assoziiert, wohingegen das SARS-CoV-2-Infektionsrisiko bei Hypertonikern nicht erhöht zu sein scheint. Nach aktueller Datenlage ist die Therapie mit ACE(Angiotensin-Converting-Enzym)-Hemmer und Angiotensin-Typ-1-Rezeptorblocker weder mit einem erhöhten SARS-CoV-2-Infektionsrisiko noch mit einem schwereren Krankheitsverlauf von COVID-19 verbunden. Eine Studie zur antihypertensiven Chronotherapie bestimmte den wissenschaftlichen Diskurs zur medikamentösen Therapie der Hypertonie. Die HYGIA-Studie kam zu der Schlussfolgerung, dass eine abendliche Medikamenteneinnahme das kardiovaskuläre Risiko von Patienten*innen mit arterieller Hypertonie reduziert. Aufgrund einiger Limitationen ist die Datenlage aktuell unzureichend, um eine routinemäßige nächtliche Gabe von antihypertensiven Medikamenten zu empfehlen. Wir werden einige der Aspekte diskutieren. Ein weiterer wissenschaftlicher Schwerpunkt lag auf den neuen Studien zur renalen Denervation. Hier kann man zusammenfassen, dass nach neuer Studienlage die katheterbasierte renale Denervation ein effektives und sicheres Verfahren zur Behandlung der arteriellen Hypertonie darstellt, das sich als alternatives Verfahren zur medikamentösen Blutdrucksenkung weiter etablieren könnte.

Obstructive Sleep Apnea-Induced Neurogenic Nocturnal Hypertension: A Potential Role of Renal Denervation?

There is a bidirectional, causal relationship between obstructive sleep apnea (OSA) and hypertension. OSA-related hypertension is characterized by high rates of masked hypertension, elevated nighttime blood pressure, a nondipper pattern of nocturnal hypertension, and abnormal blood pressure variability. Hypoxia/hypercapnia-related sympathetic activation is a key pathophysiological mechanism linking the 2 conditions. Intermittent hypoxia also stimulates the renin-angiotensin-aldosterone system to promote hypertension development. The negative and additive cardiovascular effects of OSA and hypertension highlight the importance of effectively managing these conditions, especially when they coexist in the same patient. Continuous positive airway pressure is the gold standard therapy for OSA but its effects on blood pressure are relatively modest. Furthermore, this treatment did not reduce the cardiovascular event rate in nonsleepy patients with OSA in randomized controlled trials. Antihypertensive agents targeting sympathetic pathways or the renin-angiotensin-aldosterone system have theoretical potential in comorbid hypertension and OSA, but current evidence is limited and combination strategies are often required in drug resistant or refractory patients. The key role of sympathetic nervous system activation in the development of hypertension in OSA suggests potential for catheter-based renal sympathetic denervation. Although long-term, randomized controlled trials are needed, available data indicate sustained and relevant reductions in blood pressure in patients with hypertension and OSA after renal denervation, with the potential to also improve respiratory parameters. The combination of lifestyle interventions, optimal pharmacological therapy, continuous positive airway pressure therapy, and perhaps also renal denervation might improve cardiovascular risk in patients with OSA.

Randomized Blinded Placebo-Controlled Trials of Renal Sympathetic Denervation for Hypertension: A Meta-Analysis

BackgroundThe efficacy of renal denervation has been controversial, but the procedure has now undergone several placebo-controlled trials. New placebo-controlled trial data has recently emerged, with longer follow-up of one trial and the full report of another trial (which constitutes 27% of the total placebo-controlled trial data). We therefore sought to evaluate the effect of renal denervation on ambulatory and office blood pressures in patients with hypertension. MethodsWe systematically identified all blinded placebo-controlled randomized trials of catheter-based renal denervation for hypertension. The primary efficacy outcome was ambulatory systolic blood pressure change relative to placebo. A random-effects meta-analysis was performed. Results6 studies randomizing 1232 patients were eligible. 713 patients were randomized to renal denervation and 519 to placebo. Renal denervation significantly reduced ambulatory systolic blood pressure (−3.52 mmHg; 95% CI −4.94 to −2.09; p < 0.0001), ambulatory diastolic blood pressure (−1.93 mmHg; 95% CI −3.04 to −0.83, p = 0.0006), office systolic blood pressure size (−5.10 mmHg; 95% CI −7.31 to −2.90, p < 0.0001) and office diastolic pressure (effect size −3.11 mmHg; 95% CI −4.43 to −1.78, p < 0.0001). Adverse events were rare and not more common with denervation. ConclusionsThe totality of blinded, randomized placebo-controlled data shows that renal denervation is safe and provides genuine reduction in blood pressure for at least 6 months post-procedure. If this effect continues in the long term, renal denervation might provide a life-long 10% relative risk reduction in major adverse cardiac events and 7.5% relative risk reduction in all-cause mortality.

Insights on safety and efficacy of renal artery denervation for uncontrolled-resistant hypertension in a high risk population with chronic kidney disease: first Italian real-world experience

AimsTo evaluate the safety and efficacy of catheter-based radiofrequency renal sympathetic denervation (RSD) in a daily practice population of patients with uncontrolled resistant hypertension, on top of medical therapy.MethodsConsecutive unselected patients with uncontrolled resistant hypertension undergoing RSD were enrolled. Office and ambulatory blood pressure (BP) measurements were collected at baseline and 3, 6 and 12 months after RSD. Efficacy was assessed even in patients with an estimated glomerular filtration rate (eGFR) below 45 mL/min/1.73 m2. Patients were defined as responders if systolic BP decreased by at least 5 mmHg at ambulatory BP or by 10 mmHg at office BP at their last follow-up visit.ResultsForty patients with multiple comorbidities underwent RSD from 2012 to 2019. Baseline office and ambulatory BP was 159.0/84.9 ± 26.2/14.9 mmHg and 155.2/86.5 ± 20.9/14.0 mmHg, respectively. At 12-month follow up a significant reduction in office and ambulatory systolic BP, respectively by − 19.7 ± 27.1 mmHg and by − 13.9 ± 23.6 mmHg, was observed. BP reduction at 12-month follow-up among patients with eGFR < 45 mL/min was similar to that obtained in patients with higher eGFR. Twenty-nine patients (74.4%) were responders. Combined hypertension, higher ambulatory systolic BP and lower E/E’ at baseline emerged as predictors of successful RSD at univariate analysis. No major complications were observed and renal function (was stable up to 12 months), even in patients with the lowest eGFR values at baseline.ConclusionRSD is safe and feasible in patients with uncontrolled resistant hypertension on top of medical therapy, even in a high-risk CKD population with multiple comorbidities, with a significant reduction in systolic BP and a trend towards a reduction in diastolic BP lasting up to 12 months.Graphic abstract

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 ).

Current Status and Future Perspectives of Renal Denervation.

Catheter-based renal denervation (RDN) therapy, a new procedure that uses radiofrequency ablation to interrupt efferent and afferent renal sympathetic nerve fibers, is a complementary or alternative treatment to antihypertensive medications for optimal control of blood pressure (BP). Although several single-arm early proof-of-concept studies showed significant BP reduction, the largest sham-controlled study using the first-generation RDN device (SYMPLICITY HTN-3) failed to significantly reduce BP in patients with resistant hypertension who were taking the guideline-based combination of antihypertensive medications. Since then, new devices and techniques have been developed to improve the efficacy and safety of RDN procedures. Sham-controlled trials using second-generation RDN devices (radiofrequency- and ultrasound-based) have provided solid evidence for their BP-lowering efficacy with and without the use of concomitant antihypertensive medication. Moreover, the safety profile of RDN in several registries and clinical trials appears to be excellent. This review summarizes the current evidence for RDN and discusses its current issues, future trials, Asian perspectives, and potential roles in both hypertension and other morbidities.

An Open-label, Single-arm, Multicenter Feasibility Study Evaluating the Safety of Catheter-based Renal Denervation with DENEX™ in Patients with Uncontrolled Hypertension on Standard Medical Therapy.

Background and ObjectivesDENEX™ is a novel renal sympathetic denervation (RDN) system that is equipped with 3 electrodes that deliver radiofrequency energy to the renal nerves along renal arteries. The purpose of this study was to evaluate the safety and efficacy of RDN with DENEX™ in resistant hypertension.MethodsThis was an open-label, single-arm, multicenter, first-in-man pilot study. Between November 2016 and May 2018, a total of 16 patients were enrolled at 4 centers in South Korea. The inclusion criteria were systolic blood pressure (SBP) ≥150 mmHg and use of 3 or more antihypertensive medications, including diuretics. The primary objective was the safety outcome of RDN with the DENEX™ system. The secondary objective was efficacy outcome based on changes of office, and 24-hour ambulatory SBP from baseline to 3 months. The patients underwent abdominal computed tomography (CT) or duplex ultrasonogram before and 6 months after RDN.ResultsNo major adverse events occurred after RDN for 6 month of follow-up period. There was no vascular complication either by CT or duplex ultrasonogram. The office SBP was significantly reduced from 164.6±11.6 mmHg at baseline to 142.0±20.4 mmHg (−24.4±24.4 mmHg, p=0.003) at 3 months. The ambulatory SBP was reduced from 151.44±12.85 mmHg at baseline to 140.0±16.5 mmHg (−13.1±18.9 mmHg, p=0.056) at 3 months.ConclusionRDN with the DENEX™ system showed a favorable safety profile in resistant hypertension. A significant reduction in office SBP and a borderline reduction in ambulatory SBP were observed.Trial RegistrationClinicalTrials.gov Identifier: NCT04248530

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.

Abstract 17044: Effect of Sham Controlled Renal Denervation in Uncontrolled Hypertension. A Systematic Review and Meta-Analysis

Introduction: Catheter-based ablation of renal artery has been studied as one of the interventions for blood pressure control in patients with uncontrolled hypertension. Previous randomized control trials (RCTs) comparing renal denervation versus sham procedure for the same have shown equivocal results. This meta-analysis summarizes the current evidence on the effect of sham-controlled renal denervation on blood pressure reduction. Methods: Pubmed, Embase and Cochrane Central databases were searched from inception until April 30, 2020. RCTs comparing catheter-based renal denervation with a sham control were included. Outcomes assessed were changes in ambulatory systolic blood pressure, change in ambulatory diastolic blood pressure, change in office systolic blood pressure and change in office diastolic blood pressure. Weighted mean differences (WMD) were calculated and pooled using inverse variance method into a random effect model meta-analysis. Results: Six studies with 1118 participants were included in the analysis. Catheter based renal denervation was associated with significant decrease in ambulatory systolic blood pressure (WMD: -3.71; 95% CI: -2.32 to -5.11, p value &lt;.00001) and ambulatory systolic blood pressure (WMD: -1.71; 95% CI: -0.59 to -2.82, p value=0.003) compared with sham. The reduction in office systolic and office diastolic blood pressure was also significantly greater with catheter renal denervation than sham control (WMD: -5.82; 95% CI: -3.67 to -7.92; p value&lt;0.00001 and WMD: -3.51; 95% CI: -2.29 to -4.73; p value&lt;0.00001 respectively) Conclusion: This meta-analysis showed significant benefit of catheter-based renal denervation for uncontrolled hypertension for all the studied outcomes. Based on this data patients with uncontrolled hypertension, on lifestyle and pharmacological management may benefit from catheter-based renal denervation

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.

Quantitative analysis of renal arterial variations affecting the eligibility of catheter-based renal denervation using multi-detector computed tomography angiography

Catheter-based renal denervation (RDN) was introduced to treat resistant hypertension. However, the reduction in blood pressure after the RDN was modest. Catheter-based RDN was performed only at main renal arteries, except for accessory and branch arteries due to the diameter being too small for the catheter to approach. Here, we retrospectively analyzed the anatomy of diverse renal arteries via 64-channel multi-detector computed tomography angiograms of 314 consecutive donors who underwent living donor nephrectomy from January 2012 to July 2017. Occurrence rates of one or more accessory renal arteries in donors were 25.3% and 19.4% on the left and right sides, respectively. Early branching rates before 25 mm from the aorta to the right and left renal arteries were 13.7% and 10.5%, respectively. Overall, 63.1% and 78.3% of donors had no accessory artery bilaterally and no branched renal artery, respectively. As a result, 47.1% had only main renal arteries without an accessory artery and early-branching artery. Approximately half of the donors had multiple small renal arteries bilaterally, for which catheter-based denervation may not be suitable. Thus, preoperative computed tomography angiography requires careful attention to patient selection, and there is a need for improved methods for denervation at various renal arteries.

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.