Endovascular Renal Denervation Research Articles

EFFECT OF RENAL DENERVATION ON BLOOD PRESSURE IN PATIENTS WITH CHRONIC KIDNEY DISEASE AND UNCONTROLLED HYPERTENSION: RESULTS OF A PROSPECTIVE RANDOMIZED SHAM-CONTROLLED STUDY

Objective: The activity of the sympathetic nervous system (SNS) is increased in patients with chronic kidney disease (CKD) and endovascular renal denervation (RDN) offers the opportunity to modulate SNS activity and thereby blood pressure. Hypothesis: In patients with CKD stage 3 and uncontrolled hypertension, endovascular ultrasound-based RDN (uRDN) reduces 24-hour ambulatory BP without adverse safety events. Design and method: In a multicenter prospective randomized clinical trial, following the criteria of a blinded sham-controlled design, patients with CKD stage 3 and uncontrolled hypertension despite prescription of 1-5 antihypertensive medications were enrolled. Patients were randomly allocated to either endovascular uRDN using the Paradise™ Renal Denervation System (ReCor Medical, Inc., Palo Alto, CA, USA) or a sham procedure restricted to renal angiopgraphy alone. The primary endpoint was the change in mean 24-hour ambulatory systolic BP at 6 months while on stable medication. Secondary endpoints were changes of other 24h ambulatory BP values, office BP and safety parameters of uRDN. Blinding was to be maintained through 6 months. Due to slow recruitment through 2 years, the trial was prematurely stopped. Results: Of 25 randomized patients (mean age 67yrs), 20 subjects had a 6 month visit per protocol. Major cause of CKD was hypertension and/or type-2 diabetes (N=13). There was no difference in clinical characteristics (eGFR, UACR, BMI, HbA1c, comorbidities), pretreatment 24 hour/day/night ambulatory and office BP between the uRDN (N=10) and the sham group (N=10). After 6 months the decrease in 24h(and day) ambulatory diastolic BP was significantly greater in the RDN compared with the sham group (p=0.035 (and 0.030)). Within the uRDN group, 24 hour (and day) ambulatory diastolic BP decreased over time compared to pretreatment values, whereas in the sham group no changes occurred. Systolic ambulatory BP decreased numerically in the uRDN group, but was not significant. No safety concerns related to uRDN emerged. Conclusions: In this randomized sham-controlled blinded study, despite its premature stop leading to a small study cohort, we observed a decrease of diastolic BP after endovascular uRDN and no safety signals in these hypertensive patients with CKD.

EFFECT OF RENAL DENERVATION ON 24H BLOOD PRESSURE PATTERN

Objective: Endovascular renal denervation (DRN) is a therapeutic approach for resistant arterial hypertension (RH). The aim of this study was to assess the effects of RDN on 24h blood pressure. Design and method: A retrospective evaluation of ABPM data at baseline and after 6 months from RDN in patients undergoing DRN between 01/01/2011 and 31/12/2021 in the Arterial Hypertension Center of Turin. Mean 24h, Daytime, Nighttime BP and HR values and short term 24h, daytime and nigthtime BP and HR varability parameters (standard deviation, dipping and coefficient of variation) were calculated. Results: The series included 14 subjects, of which 8 (57%) were female and with an average age 54±10 years. The number of antihypertensive drugs before renal denervation was 5.7±1.0. At baseline office BP was 188/113±22±18 mmHg and ABPM 24h BP was 150/92±21±16 mmHg. Patients were considered as responders if a reduction of least 10 mmHg in systolic blood pressure (PAS) at 24h Blood Pressure Monitoring at six months from RDN was obtained. From a safety point of view, there were no short-term or long-term complications. The responders at six months were 66%. Non-responders showed an increased blood pressure variability compared to responders at baseline and only one was dipper. The responders had a statistically significant redution of SD24h after DRN, an increased average nocturnal blood pressure drop and a lower pressure variability. While in non-responders no redution in SDnight, SDday and coefficient of variation was found, by contrast all of them become dippers because mean daytime SBP increase. Conclusions: In conclusion, pressure variability (SD24h and coefficient of variation) is globally reduced in the denerved patients, this trend is particularly present in responders. The non-responders have an increased BP variability at baseline without decreasing after DRN. These results suggest that, when effective, DRN can reduce both BP levels and BP variability, thus may have an important effect in reducing cardiovascular risk.

Effects of Renal Denervation vs Sham in Resistant Hypertension After Medication Escalation

Although early trials of endovascular renal denervation (RDN) for patients with resistant hypertension (RHTN) reported inconsistent results, ultrasound RDN (uRDN) was found to decrease blood pressure (BP) vs sham at 2 months in patients with RHTN taking stable background medications in the Study of the ReCor Medical Paradise System in Clinical Hypertension (RADIANCE-HTN TRIO) trial. To report the prespecified analysis of the persistence of the BP effects and safety of uRDN vs sham at 6 months in conjunction with escalating antihypertensive medications. This randomized, sham-controlled, clinical trial with outcome assessors and patients blinded to treatment assignment, enrolled patients from March 11, 2016, to March 13, 2020. This was an international, multicenter study conducted in the US and Europe. Participants with daytime ambulatory BP of 135/85 mm Hg or higher after 4 weeks of single-pill triple-combination treatment (angiotensin-receptor blocker, calcium channel blocker, and thiazide diuretic) with estimated glomerular filtration rate (eGFR) of 40 mL/min/1.73 m2 or greater were randomly assigned to uRDN or sham with medications unchanged through 2 months. From 2 to 5 months, if monthly home BP was 135/85 mm Hg or higher, standardized stepped-care antihypertensive treatment starting with aldosterone antagonists was initiated under blinding to treatment assignment. uRDN vs sham procedure in conjunction with added medications to target BP control. Six-month change in medications, change in daytime ambulatory systolic BP, change in home systolic BP adjusted for baseline BP and medications, and safety. A total of 65 of 69 participants in the uRDN group and 64 of 67 participants in the sham group (mean [SD] age, 52.4 [8.3] years; 104 male [80.6%]) with a mean (SD) eGFR of 81.5 (22.8) mL/min/1.73 m2 had 6-month daytime ambulatory BP measurements. Fewer medications were added in the uRDN group (mean [SD], 0.7 [1.0] medications) vs sham (mean [SD], 1.1 [1.1] medications; P = .045) and fewer patients in the uRDN group received aldosterone antagonists at 6 months (26 of 65 [40.0%] vs 39 of 64 [60.9%]; P = .02). Despite less intensive standardized stepped-care antihypertensive treatment, mean (SD) daytime ambulatory BP at 6 months was 138.3 (15.1) mm Hg with uRDN vs 139.0 (14.3) mm Hg with sham (additional decreases of -2.4 [16.6] vs -7.0 [16.7] mm Hg from month 2, respectively), whereas home SBP was lowered to a greater extent with uRDN by 4.3 mm Hg (95% CI, 0.5-8.1 mm Hg; P = .03) in a mixed model adjusting for baseline and number of medications. Adverse events were infrequent and similar between groups. In this study, in patients with RHTN initially randomly assigned to uRDN or a sham procedure and who had persistent elevation of BP at 2 months after the procedure, standardized stepped-care antihypertensive treatment escalation resulted in similar BP reduction in both groups at 6 months, with fewer additional medications required in the uRDN group. ClinicalTrials.gov Identifier: NCT02649426.

Renal Denervation for Resistant Hypertension: A Concise Update on Treatment Options and the Latest Clinical Evidence.

Evidence from recent sham-controlled trials supports the use of endovascular renal denervation (RDN) to lower blood pressure in general as well as in treatment-resistant hypertension. According to recent studies, the effects of RDN are long lasting. Newer technologies using multipolar radiofrequency catheters and an additional ablation of the renal side branches as well as ultrasound with improved circumferential tissue penetration have made these advances possible. This has initiated a change of the perspective on RDN in clinical guidelines and has thereby set a cornerstone for a broader clinical application of RDN in the future.

Endovascular Renal Denervation Efficacy in a Five-Year Follow-Up

Endovascular Renal Denervation Efficacy in a Five-Year Follow-Up

Renal Artery Variations in Patients With Mild-to-Moderate Hypertension From the RADIANCE-HTN SOLO Trial

PurposeTo assess the variability of renal artery (RA) anatomy and presence of RA-pathology in patients with mild-to-moderate hypertension enrolled in the RADIANCE-HTN SOLO trial. BackgroundRADIANCE-HTN SOLO was a multicenter, international, blinded, randomized, sham-controlled trial evaluating ultrasound-based endovascular renal denervation (RDN) in patients with mild-to-moderate hypertension while off antihypertensive medications. MethodsEligible subjects had pre-randomization renal CT- or MR- angiography (CTA, MRA) to confirm anatomic suitability and to define RA ablation sites. All images were sent for independent review for evaluation of RA anatomy and other vascular pathology. ResultsA total of 324 patients underwent RA imaging (282 CTA and 42 MRA). Of those, 178 had simple anatomy with a single left and single right RA with mean diameters of 5.4 ± 0.9 and 5.1 ± 0.8 mm and mean lengths of 40.0 ± 12.9 and 52.0 ± 13.1 mm, respectively. Twenty-seven patients (8.3%) had unilateral or bilateral dual RAs with mean diameters of 4.0 ± 0.9 mm on the left and 3.9 ± 0.9 mm on the right. Forty percent (129/324) of patients had at least 1 accessory RA, with mean accessory diameters of 2.4 ± 0.8 mm on the left and 2.3 ± 0.8 mm on the right. Twenty-eight patients (8.6%) had at least 1 short (<25 mm) main RA. Incidental findings included: 9 patients (2.8%) with atherosclerotic RA stenosis ≥30%, 9 patients (2.8%) with fibromuscular dysplasia of RA and 2 patients (0.6%) with kidney and adrenal gland tumors. ConclusionsPre-procedure CTA or MRA imaging is a valuable aid in assessing RA anatomy prior to RDN because of variable RA anatomy. CTA or MRA may detect RA lesions, and renal or adrenal tumors which may need additional workup prior to consideration of RDN. Clinical trial registrationClinicalTrials.gov NCT02649426.

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.

Anatomically optimized distal renal denervation — sustained blood pressure lowering efficacy during 3 years after the intervention

Aim. To test the hypothesis that anatomical optimisation of radiofrequency renal denervation (RDN) by redistribution of treatment to segmental branches of the renal artery causes a durable increase in the efficacy of the intervention.Methods. A double-blind randomised control study in parallel groups with a 3-year follow-up was performed in patients with apparent resistant hypertension (office systolic BP ≥160 or diastolic BP ≥100 mmHg despite stable treatment with ≥3 drugs, including a diuretic). Exclusion criteria were secondary hypertension, mean 24-h systolic BP &lt;135 mmHg, eGFR &lt;30 mL/min/m2 and severe comorbidity increasing procedural risks (investigator’s assessment). Eligible patients were randomised 1:1 into distal RDN or RDN in the main trunk of the renal artery. Treatment assignment was done in the operation room immediately before the procedure. For the duration of the study, the assigned treatment was unknown to patients, physicians and other outcome assessors. Long-term efficacy of the procedure was measured by changes in BP (office and ambulatory), whereas safety was assessed by changes in the 24-h protein excretion, serum creatinine and eGFR 3 years post-procedure.Results. Of the 55 randomised patients, 39 (71%) completed a 3-year assessment (21 after distal RDN and 18 after RDN in the main trunk of the renal artery). Compared to baseline, the mean 24-h BP remained significantly lowered in the distal RDN group by −16.9 (95% CI −27.3;−6.5)/−8.5 (95% CI −14.2;−2.9) mmHg, p = 0.002/0.004 (systolic/diastolic, respectively). The lowering of the mean 24-h BP was almost twofold less and non-significant in the group of RDN in the main trunk of the renal artery: −8.7 (95% CI −19.6;2.2)/−5.8 (95% CI −11.8;0.1).Conclusion. Anatomical optimisation of endovascular renal denervation produces a powerful and sustained increase in the efficacy of the intervention. Received 19 May 2020. Revised 10 July 2020. Accepted 7 September 2020. Funding: The study did not have sponsorship. Conflict of interest: Authors declare no conflict of interest. Clin.Trials.gov Identifier: NCT02667912. Author contributionsConception and design: S.E. PekarskiyData collection and analysis: S.E. Pekarskiy, A.E. Baev, A.Yu. Falkovskaya, E.S. Sitkova, I.V. Zyubanova, V.A. Lichikaki, V.F. MordovinStatistical analysis: S.E. PekarskiyDrafting the article: S.E. Pekarskiy, A.E. BaevCritical revision of the article: S.V. PopovFinal approval of the version to be published: S.E. Pekarskiy, A.E. Baev, A.Yu. Falkovskaya, E.S. Sitkova, I.V. Zyubanova, V.A. Lichikaki, V.F. Mordovin, S.V. Popov

MRI-based detection of renal artery abnormalities related to renal denervation by catheter-based radiofrequency ablation in drug resistant hypertensive patients.

Endovascular renal denervation (RDN) using catheter-based radiofrequency (RF) ablation has emerged as a potential treatment option for drug-resistant hypertension. Its efficacy is currently under debate. We aimed to evaluate the capability of contrast-enhanced magnetic resonance imaging (MRI) to assess the effects of RDN on the renal arterial wall in patients presenting with drug-resistant hypertension. Patients were included prospectively following institutional review board approval and written informed consent. Renal arteries were imaged using a two-dimensional T1-weighted TSE sequence pre- and post-administration of a gadolinium-based contrast agent, before (D0), 2 days (D2) and 6 months (M6) after RDN. Mean enhancement of the wall (mENH) and mean wall thickness (mWT) were compared across time using an ANOVA with repeated measures and post-hoc paired t-test. Follow-up was completed for 23 patients (median age, 57 years; 16 men). The mENH at D2 (96.3 ± 36.0 %) was significantly higher than at D0 (61.1 ± 26.3%, p < 0.001) and M6 (66.1±22.7%, p < 0.001). Similarly, mWT was significantly higher at D2 (3.1 ± 0.4 m) than at D0 (2.7 ± 0.4mm, p < 0.001) and M6 (2.9 ± 0. 5 mm, p = 0.002). MRI demonstrated abnormalities of the arterial wall 2 days after RDN that had resolved at 6 months. • Contrast-enhanced MRI provides anatomic evidence of renal artery RF ablation • Temperature increase related to RF ablation induces transient arterial wall inflammation • Morphological effects observed 2 days post RF ablation are not visible after 6 months.

Pathophysiologic Mechanisms in Heart Failure: Role of the Sympathetic Nervous System

The syndrome of heart failure involves complex pathophysiologic mechanisms and is associated with extremely high-morbidity, mortality and economic costs. This growing global epidemic has diverse etiologies and is fundamentally characterized by dyshomeostasis between heart and kidneys, leading to development and progression of the cardiorenal syndrome. Excessive and sustained sympathoexcitation has emerged as a single prominent factor involved in the structural and functional dysfunction of multiple organ systems during this disease. Studies in experimental models of heart failure indicate that ablation of the renal nerves may help restore renal sodium and water equilibrium as well as the attenuation of adverse cardiac remodeling. With the recent development of minimally invasive endovascular renal denervation in humans, it is anticipated that this technology would become a novel and important paradigm shift in the management of heart failure.

A rational anaesthesia care program for endovascular renal denervation

A rational anaesthesia care program for endovascular renal denervation

CRT-300.13 Renal Denervation by Chemical Neurolysis (Preliminary Data From the PEREGRINE Trial)

Alcohol-mediated endovascular renal denervation (RDN) using the Peregrine System™ has been shown to be safe, with a good indication of effectiveness as measured by office blood pressure (OBP). A safety and performance trial is on-going; we report preliminary data from the first 10 subjects. The

Innervation Patterns May Limit Response to Endovascular Renal Denervation

BackgroundRenal denervation is a new interventional approach to treat hypertension with variable results. ObjectivesThe purpose of this study was to correlate response to endovascular radiofrequency ablation of renal arteries with nerve and ganglia distributions. We examined how renal neural network anatomy affected treatment efficacy. MethodsA multielectrode radiofrequency catheter (15 W/60 s) treated 8 renal arteries (group 1). Arteries and kidneys were harvested 7 days post-treatment. Renal norepinephrine (NEPI) levels were correlated with ablation zone geometries and neural injury. Nerve and ganglion distributions and sizes were quantified at discrete distances from the aorta and were compared with 16 control arteries (group 2). ResultsNerve and ganglia distributions varied with distance from the aorta (p < 0.001). A total of 75% of nerves fell within a circumferential area of 9.3, 6.3, and 3.4 mm of the lumen and 0.3, 3.0, and 6.0 mm from the aorta. Efficacy (NEPI 37 ng/g) was observed in only 1 of 8 treated arteries where ablation involved all 4 quadrants, reached a depth of 9.1 mm, and affected 50% of nerves. In 7 treated arteries, NEPI levels remained at baseline values (620 to 991 ng/g), ≤20% of the nerves were affected, and the ablation areas were smaller (16.2 ± 10.9 mm2) and present in only 1 to 2 quadrants at maximal depths of 3.8 ± 2.7 mm. ConclusionsRenal denervation procedures that do not account for asymmetries in renal periarterial nerve and ganglia distribution may miss targets and fall below the critical threshold for effect. This phenomenon is most acute in the ostium but holds throughout the renal artery, which requires further definition.

Proceedings from the Society of Interventional Radiology Foundation Research Consensus Panel on Renal Sympathetic Denervation

SPECIAL COMMUNICATION Proceedings from the Society of Interventional Radiology Foundation Research Consensus Panel on Renal Sympathetic Denervation John F. Angle, MD, Ethan A. Prince, MD, Alan H. Matsumoto, MD, Thomas E. Lohmeier, PhD, Andrew M. Roberts, PhD, Sanjay Misra, MD, Mahmood K. Razavi, MD, Richard E. Katholi, MD, Shawn N. Sarin, MD, Domenic A. Sica, MD, Kalyanam Shivkumar, and Kamran Ahrar, MD ABBREVIATIONS BP = blood pressure, CHF = congestive heart failure, HTN = hypertension, MSNA = muscle sympathetic nerve activity, NE = norepinephrine, LV = left ventricular, OSA = obstructive sleep apnea, PET = positron emission tomography, PAREPET = prediction of arrhythmic events with positron emission tomography, RCP = research consensus panel, RDN = renal denervation, RSNA = renal sympathetic nerve activity In 1948, Smithwick and others (1,2) reported on oper- ative thoracolumbar sympathectomy to treat hyperten- sion (HTN). In a study of patients with uncontrolled HTN who underwent thoracolumbar sympathectomy, 45% of 1,266 patients maintained significant improve- ment in blood pressure (BP) 5 years later (3). However, this procedure was also associated with significant morbidity and orthostatic hypotension and was abandoned in the 1960s with the widespread advan- cements in, and availability of, effective pharmacologic therapy. In the 1970s, operative ligation of the sym- pathetic fibers in the perirenal space was considered a From the Department of Radiology, Division of Vascular and Interventional Radiology (J.F.A., A.H.M.), University of Virginia Health System, 1215 Lee Street, Charlottesville, VA 22908; Department of Radiology, Division of Vascular and Interventional Radiology (E.A.P.), Brown University, Providence, Rhode Island; Department of Physiology (T.E.L.), University of Mississippi, Jackson, Mississippi; Department of Physiology (A.M.R.), University of Louisville, Louisville, Kentucky; Department of Radiology, Division of Vascular and Interventional Radiology (S.M.), Mayo Clinic, Rochester, Minnesota; Vascular & Interventional Specialists of Orange County, Inc. (M.K.R.), Los Angeles, California; Department of Cardiology (R.E.K.), Prairie Heart Institute at St. John's Hospital, Springfield, Illinois; Department of Radiology, Division of Vascular and Interventional Radiology (S.N.S.), George Washington Uni- versity, Washington, D.C.; Department of Internal Medicine, Division of Nephrology (D.A.S.), Virginia Commonwealth University, Richmond, Virginia; Department of Internal Medicine, Division of Cardiology (K.S.), University of California, Los Angeles, Los Angeles, California; Department of Radiology (K.A.), Division of Vascular and Interventional Radiology, University of Texas, MD Anderson Cancer Center, Houston, Texas. Received December 13, 2013; final revision received and accepted December 27, 2013. Address correspon- dence to J.F.A.; E-mail: Jfa3h@virginia.edu None of the authors have identified a conflict of interest. & SIR, 2014 J Vasc Interv Radiol 2014; 25:497–509 http://dx.doi.org/10.1016/j.jvir.2013.12.572 contributor to the benefits of renal artery surgery for treatment of renovascular HTN or chronic kidney disease (4). More recently, convincing evidence has emerged that chronic elevation of sympathetic nervous system activity is a major contributor to the complex pathophysiology of essential HTN and in particular resistant HTN (5,6). In 2007, an endovascular radiofrequency (RF) abla- tion catheter that could safely reduce renal sympathetic innervation was first demonstrated (7). Transcatheter endovascular renal denervation (RDN) using RF ablation was used clinically shortly thereafter and has since demonstrated dramatic short-term and midterm benefits for the treatment of resistant HTN (8–10). The breadth and number of clinical trials in this field have expanded rapidly. Additional findings from mostly small, uncontrolled, observational studies have sug- gested numerous favorable cardiovascular responses to RDN that are in need of corroboration (11–16). The potential for early clinical adoption has also driven the development and clinical testing of multiple new devices for ablation of the perirenal sympathetic nerve fibers Many questions remain about RDN, including mech- anisms of action of RDN, local renal versus systemic effects of denervation, local long-term effects on the vascular endothelium and wall, methods for selecting appropriate candidates for RDN, evaluation of potential alternative clinical indications, comparisons of study populations and devices, extent of RDN, and develop- ment of better outcome measures after RDN (6,19,20). The goal of this article is to report on the proceedings of a Society of Interventional Radiology (SIR) Foundation Research Consensus Panel (RCP) on RDN. A secondary

Endovascular renal denervation: a novel sympatholytic with relevance to chronic kidney disease.

Endovascular renal denervation (sympathectomy) is a novel procedure developed for the treatment of resistant hypertension. Evidence suggests that it reduces both afferent and efferent sympathetic nerve activity, which may offer clinical benefit over and above any blood pressure-lowering effect. Studies have shown objective improvements in left ventricular mass, ventricular function, central arterial stiffness, central haemodynamics, baroreflex sensitivity and arrhythmia frequency. Benefits have also been seen in insulin resistance, microalbuminuria and glomerular filtration rate. In chronic kidney disease, elevated sympathetic activity has been causally linked to disease progression and cardiovascular sequelae. Effecting a marked reduction in sympathetic hyperactivity may herald a significant step in the management of this and other conditions. In this in-depth review, the pathophysiology and clinical significance of the sympatholytic effects of endovascular renal denervation are discussed.

Abstract 287: Radiofrequency Renal Nerve Ablation Attenuates Hypertension in Spontaneously Hypertensive Rats (SHR)

Radiofrequency catheter ablation (RF-ABL) of the renal arteries decreases blood pressure in patients with drug-resistant hypertension. This study investigated whether RF-ABL of the renal arteries alters blood pressure (BP) in an animal model of essential hypertension, the spontaneously hypertensive rat (SHR). Methods Nineteen-week old male SHR were instrumented with radio-telemetry probes for chronic measurement of BP (Systolic, SBP; Diastolic, DBP). After 1-week, control BP was measured in rats for 3 days. The next day SHR were anesthetized and randomly received either bilateral Sham-ABL (n=5) or RF-ABL (n=6) of the renal arteries (Biosense Webster Stockert 70 generator and RF-probe). The tip of the RF-probe was applied externally to a small dissected segment of each renal artery and stimulated circumferentially (10 Watts). BP was then measured three times a week for 8 weeks. Results In anesthetized hypertensive SHR, RF-ABL of a single renal artery did not alter BP. In contrast, subsequent RF-ABL of the contralateral renal artery produced an immediate (&lt;15 seconds) decrease in mean arterial blood pressure (MAP, range Δ -60 to -100 mmHg). BP in hypertensive SHR was not altered during or after the Sham-RF procedure. In conscious SHR, BP was significantly decreased the day after RF-ABL (153±8/102±4 mmHg) and throughout the post-ABL study (4-week SBP/DBP, 173±7/120±5; 8-weeks, 171±6/116±4 mmHg) compared to pre-ABL control levels (SBP/DBP, 187±9/130±5 mmHg). At the end of week-1 the peak increase in MAP to cage switch stress was significantly blunted and the time to return to basal BP was shortened in RF-ABL (peak Δ 18±5 mmHg; 30-min to basal) vs. Sham-ABL (peak Δ 32±3 mmHg; 70-min to basal). At the end of week-8, the hypotensive response to i.p. chlorisondamine was blunted in RF-ABL (Δ -39±4 mmHg) vs. Sham-ABL rats (Δ -53±2 mmHg). Conclusions These data demonstrate that in hypertensive SHR, bilateral RF-ABL of the renal arteries produces, presumably via blockade of renal sympathetic afferent/efferent neural pathways, a reduction in BP, which by 4-weeks is reset to a lower basal level. These findings indicate that RF-ABL can be used in rodents to investigate the therapeutic mechanisms by which endovascular renal denervation reduces blood pressure in hypertension.

Prevalence of Resistant Hypertension and Eligibility for Catheter-Based Renal Denervation in Hypertensive Outpatients

Studies of endovascular renal denervation (RDN) have demonstrated significant blood pressure reduction in eligible patients with resistant hypertension. These trials have used stringent inclusion and exclusion criteria in patient enrollment, potentially selecting for a small subset of patients with resistant hypertension. In this study, we examined the changes in estimated prevalence of resistant hypertension when using increasingly stringent definitions of resistant hypertension in a fixed population and assessed the generalizability of RDN when applying study criteria to a community-based hypertensive population. A retrospective chart review was done of hypertensive outpatients. Four increasingly stringent interpretations of the American Heart Association definition of resistant hypertension were used to calculate prevalence estimates. Patients eligible for RDN were identified using criteria from SYMPLICITY HTN-3. Demographic and clinical characteristics were compared. We identified 1,756 hypertensive outpatients; 55.0% were male, 53.9% were white, and subjects had a mean age of 66.6 ± 12.5 years and a body mass index (BMI) of 30.1 ± 10.7 kg/m(2). Only 14 (0.8%) were eligible for RDN. Among these patients, 10 (71.4%) were female and all were black, with a mean age of 69.9 ± 8.8 and BMI of 35.7 ± 6.6. Congestive heart failure was more common in patients eligible for RDN. Patients eligible for RDN based on published studies represent an exceedingly small proportion of the total hypertensive population. Further studies are necessary to determine if the benefits of RDN can be generalized to a broader range of hypertensive patients than those included in previous trials.

Pathophysiology of renal denervation procedures: from renal nerve anatomy to procedural parameters

Endovascular renal denervation techniques have been clinically adopted for the treatment of resistant arterial hypertension with great success. Despite the favourable early results achieved with this technology, a clear understanding of the pathophysiology underlying this novel treatment is lacking. In addition, non-responsiveness to renal denervation remains a nidus for treatment failure in distinct patients. In search of meaningful surrogate parameters relating to treatment responsiveness, the current article reviews the existing knowledge on renal nerve anatomy, changes occurring after denervation and procedural parameters collected during denervation. From preclinical experience, the most reliable morphological parameter reflecting successful renal denervation is the presence of axonal degeneration. Most procedural and clinical parameters need extended investigation before adopting them as potential surrogate parameters for successful renal denervation. As a consequence, there is an imperative need for dedicated research revealing the pathophysiology of renal denervation procedures. In this regard, close co-operation of engineers, researchers and clinicians is warranted to turn renal denervation into a milestone treatment of arterial hypertension.

Electric Nerve Stimulation to Monitor the Efficacy of Renal Denervation

See related article, pp 450–456 In 2009, Krum et al1 reported a substantial blood pressure decrease (−27/17 mm Hg at 12 months) after percutaneous radiofrequency catheter-based renal sympathetic denervation in a cohort of 45 patients with resistant hypertension. One year later, the results of this proof-of-concept study were confirmed in 106 resistant hypertensive patients randomized 1:1 to renal denervation plus previous drug treatment versus drug treatment alone, with a blood pressure decrease of −32/12 mm Hg at 6 months in the renal denervation group ( P <0.0001), contrasting with virtually unchanged blood pressure in the control group (SYMPLICITY HTN-2).2 However, the SYMPLICITY studies have important limitations, addressed in detail elsewhere.3 Accordingly, there is a growing consensus that renal denervation should remain the ultima ratio in resistant hypertension3 and should only be administered by multidisciplinary teams in tertiary referral centres, after careful patient selection. Unfortunately, besides higher baseline systolic blood pressure and use of central sympatholytic agents,4 SYMPLICITY studies failed to identify independent predictors of blood pressure response after renal denervation. Therefore, patient selection is almost entirely based on negative criteria, such as exclusion of patients with secondary and white coat hypertension or with narrow or too short renal arteries. In individual cases, whether lack of blood pressure decrease after renal denervation is due to poor contribution of the sympathetic system to the pathogenesis or the maintenance of hypertension, …