Denervation In Patients Research Articles

Blood pressure variability after catheter-based renal sympathetic denervation in patients with resistant hypertension.

Renal denervation (RDN) reduces sympathetic activity and blood pressure (BP) in patients with resistant hypertension. Increased 24-h BP variability is associated with adverse cardiovascular outcomes and related to sympathetic activation. This multicenter study investigated the effect of RDN on BP variability in 84 patients with uncontrolled hypertension (office systolic BP ≥140 mmHg) despite treatment with greater than three antihypertensive agents. BP variability was assessed by means of standard deviation, coefficient of variation (standard deviation/mean), and average real variability of 24-h ambulatory SBP at 3-month and 6-month follow-up. RDN significantly reduced office BP by 17/6 mmHg at 3-month and 19/7 mmHg at 6-month follow-up (P < 0.001 for all) and 24-h ambulatory BP by 9/5 mmHg (P < 0.001/P = 0.001) after 3 months and 12/7 mmHg (P < 0.001/P < 0.001) after 6 months. Standard deviation significantly decreased from 17.1 to 14.9 mmHg (P = 0.008) and 15.3 mmHg (P = 0.037), consistent with a reduction of coefficient of variation from 0.116 to 0.103 (P = 0.035) and 0.104 (P = 0.071) and average real variability from 12.3 to 10.9 (P = 0.029) and 11.0 (P = 0.054) after 3-month and 6-month, respectively. Interestingly, also BP nonresponders (change in office systolic BP < 10 mmHg after 6 months) showed a significant reduction of standard deviation after 3 months (P = 0.041, n = 26) and a borderline significant reduction at 6-month (P = 0.057, n = 28). RDN reduces office and ambulatory BP and BP variability in patients with resistant hypertension. Improvement in BP variability was also documented in patients characterized as office BP nonresponders after 6 months.

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

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

P-182: Analysis of eligibility criteria for renal sympathetic denervation in patients with resistant hypertension

Renal sympathetic denervation (RDN) is indicated for the treatment of resistant hypertension (RH). The RH is true when the causes of pseudo-hypertension as well as other modifiable causes, e. g secondary hypertension or poor adherence, are excluded. In the clinical practice there are patients who due to polyintolerances or allergies can't be treated with the maximal therapy and therefore are not considered as RH – patients in accordance with the current definition. Since they are also very difficult to treat with medical therapy we also considered them in this study as eligible for renal denervation. The goal of the study is to assess the percentage of eligibility to RDN and analyze the exclusion criteria in a group of resistant hypertensive patients. Between 2011 and 2014 we retrospectively reviewed patients who came to our Center for an evaluation for RDN. We considered patients with office blood pressure ≥160 mmHg and patients with severe hypertension treated with fewer drugs because of poly-intolerances / allergies as eligible. At first a specialist optimized drug therapy and subsequently reassessed the blood pressure response. For each patient a diagnostic examination was conducted in order to rule out secondary hypertension. To exclude a white coat effect the patients each performed an arterial blood pressure monitoring (ABPM). In patients with true resistant hypertension, a CT angiography was performed in order to check the renal anatomic criteria of eligibility to the RDN. Out of the 35 participating patients, 27 were considered unsuitable for the RDN for at least one of these causes: blood pressure control with optimization of drug therapy (52%), evidence of white coat effect (22%), secondary hypertension (22%), lack of true resistant hypertension (18%), absence of consent to the procedure (29%). All eight eligible patients were sent by specialist centers while the major part of the unsuitable patients was sent by GPs. Before giving the indication for RDN, it is necessary to carefully select patients with RH as most of the patients proved ineligible due to inadequacy of drug therapy and white coat hypertension.

MR Imaging of Brachial Plexus and Limb-Girdle Muscles in Patients with Amyotrophic Lateral Sclerosis.

To assess brachial plexus magnetic resonance (MR) imaging features and limb-girdle muscle abnormalities as signs of muscle denervation in patients with amyotrophic lateral sclerosis (ALS). This study was approved by the local ethical committees on human studies, and written informed consent was obtained from all subjects before enrollment. By using an optimized protocol of brachial plexus MR imaging, brachial plexus and limb-girdle muscle abnormalities were evaluated in 23 patients with ALS and clinical and neurophysiologically active involvement of the upper limbs and were compared with MR images in 12 age-matched healthy individuals. Nerve root and limb-girdle muscle abnormalities were visually evaluated by two experienced observers. A region of interest-based analysis was performed to measure nerve root volume and T2 signal intensity. Measures obtained at visual inspection were analyzed by using the Wald χ(2) test. Mean T2 signal intensity and volume values of the regions of interest were compared between groups by using a hierarchical linear model, accounting for the repeated measurement design. The level of interrater agreement was very strong (κ = 0.77-1). T2 hyperintensity and volume alterations of C5, C6, and C7 nerve roots were observed in patients with ALS (P < .001 to .03). Increased T2 signal intensity of nerve roots was associated with faster disease progression (upper-limb Medical Research Council scale progression rate, r = 0.40; 95% confidence interval: 0.001, 0.73). Limb-girdle muscle alterations (ie, T2 signal intensity alteration, edema, atrophy) and fat infiltration also were found, in particular, in the supraspinatus muscle, showing more frequent T2 signal intensity alterations and edema (P = .01) relative to the subscapularis and infraspinatus muscles. Increased T2 signal intensity and volume of brachial nerve roots do not exclude a diagnosis of ALS and suggest involvement of the peripheral nervous system in the ALS pathogenetic cascade. MR imaging of the peripheral nervous system and the limb-girdle muscle may be useful for monitoring the evolution of ALS and distinguishing patients with ALS from those with inflammatory neuropathy, respectively.

Abstract 10452: The SYMPLICITY HF Feasibility Study: Twelve Month Outcomes of Renal Denervation in Patients With Chronic Heart Failure and Renal Impairment

Introduction: Renal dysfunction often develops in patients with heart failure with low ejection fraction due to hemodynamic and neurohumoral dysfunction leading to increased risk for mortality. Methods: The multi-center, prospective, open label Renal Denervation in Patients With Chronic Heart Failure &amp; Renal Impairment (SYMPLICITY HF) trial enrolled NYHA Class II-III patients with left ventricular ejection fraction (LVEF) &lt;40% and estimated glomerular filtration rate (eGFR) 30 to 75 mL/min/1.73m 2 . Subjects with systolic blood pressure &lt; 90 mm Hg were excluded. The primary objective was to evaluate both the safety and physiologic response of renal denervation therapy on cardiac and renal function with the Symplicity™ renal denervation system using the Symplicity Flex™ catheter (Medtronic, Inc). Results: A total of 39 patients were enrolled (Table). No vascular complications occurred during the procedure. Available at AHA 2015 will be outcomes to 12 months follow up, including safety, cardiac function by echocardiography, and renal function by eGFR. Additionally, 9 subjects participated in a sub study that evaluated cardiac and renal noradrenaline spillover, muscle sympathetic nerve activity, and electrophysiological parameters by Holter monitor. Conclusions: Twelve-month outcomes in SYMPLICITY HF will provide initial insights into the safety and cardiac and renal physiologic impact of renal denervation in patients with heart failure.

Renal Denervation in Patients With Uncontrolled Hypertension and Confirmed Adherence to Antihypertensive Medications.

Renal denervation (RDN) has emerged as a potential device-based treatment for resistant hypertension. The authors present their experience of the use of catheter-based RDN as part of routine clinical care in two specialist hypertension clinics. Thirty-four patients with uncontrolled hypertension underwent RDN. All patients had ambulatory blood pressure (BP) monitoring and directly observed medication administration prior to the procedure to exclude white-coat hypertension and nonadherence, respectively. Overall, there was a significant change in clinic systolic BP of -15.1 mm Hg (95% confidence interval, -23.4 to -6.8; P=.001) and clinic diastolic BP of -6.2 mm Hg (95% confidence interval, -11.5 to -0.9; P=.02) 6 months postprocedure, and a nonsignificant change in daytime ambulatory BP of -5.4/-2.9 mm Hg. Eighteen patients (51.4%) showed a significant reduction in their clinic systolic BP (≥10 mm Hg) and 16 (47%) had a significant reduction in their daytime ambulatory systolic BP (≥5 mm Hg) at 6 months.

Renal artery anatomy affects the blood pressure response to renal denervation in patients with resistant hypertension

BackgroundRenal denervation (RDN) has been shown to reduce blood pressure (BP), muscle sympathetic nerve activity (MSNA) and target organ damage in patients with resistant hypertension (RH) and bilateral single renal arteries. The safety and efficacy of RDN in patients with multiple renal arteries remains unclear. MethodsWe measured office and 24-hour BP at baseline, 3 and 6months following RDN in 91 patients with RH, including 65 patients with single renal arteries bilaterally (group 1), 16 patients with dual renal arteries on either one or both sides (group 2) and 10 patients with other anatomical constellations or structural abnormalities (group 3). Thirty nine out of 91 patients completed MSNA at baseline and follow-up. ResultsRDN significantly reduced office and daytime SBP in group 1 at both 3 and 6months follow-up (P<0.001) but not in groups 2 and 3. Similarly, a significant reduction in resting baseline MSNA was only observed in group 1 (P<0.05). There was no deterioration in kidney function in any group. ConclusionWhile RDN can be performed safely irrespective of the underlying renal anatomy, the presence of single renal arteries with or without structural abnormalities is associated with a more pronounced BP and MSNA lowering effect than the presence of dual renal arteries in patients with RH. However, when patients with dual renal arteries received renal nerve ablation in all arteries there was trend towards a greater BP reduction. Insufficient renal sympathetic nerve ablation may account for these differences.

Spironolactone for resistant hypertension—hard to resist?

Spironolactone for resistant hypertension—hard to resist?

Quality of life after videoscopic left cardiac sympathetic denervation in patients with potentially life-threatening cardiac channelopathies/cardiomyopathies

Left cardiac sympathetic denervation (LCSD) provides an additive or potentially alternative treatment option for patients with life-threatening cardiac channelopathies/cardiomyopathies. We sought to examine the effects of LCSD on quality of life (QOL). From November 2005 to May 2013, 109 patients who underwent LCSD were subsequently sent postoperative QOL surveys. Of 109 patients, 8 (7%) could not be contacted. Of the remaining 101 patients, 62 returned surveys (response rate 61%). There were an average of 4.1 ± 1.8 self-reported side effects immediately after LCSD. The most common anticipated side effects included unilateral hand dryness, color or temperature variance between sides of the face, and abnormal sweating. Although parent-reported pediatric physical QOL scores were lower than national norms, there were no differences in psychosocial QOL or disability scores (P = .09 and .33, respectively). QOL scores for adult patients were not significantly different from a US normative sample. Adult LCSD patients reported less disability than a US normative sample (P < .01). There was no correlation between QOL scores and the presence of anticipated side effects. However, among the subset of pediatric patients who continued to receive ventricular fibrillation-terminating implantable cardioverter-defibrillator shocks after LCSD, there was a correlation between their disability scores and the number of reported shocks (Spearman correlation = 0.56). The majority of patients/parents reported that they were very or somewhat satisfied with their surgery (or their child's surgery) and would definitely or probably recommend LCSD to another patient. Despite the anticipated side effects associated with LCSD, patients are satisfied with their surgery and indicate that they would recommend the surgery to another patient.

Plasma renalase concentration before and after radiofrequency renal denervation in patients with resistant hypertension.

Plasma renalase concentration before and after radiofrequency renal denervation in patients with resistant hypertension

Renal Denervation: Past, Present, and Future

Hypertension remains a leading cause of cardiovascular morbidity and mortality worldwide. It is estimated that 12.8% of hypertensive adults have resistant hypertension. The sympathetic nervous system is a well-known contributor to the pathophysiology of resistant hypertension. Renal denervation has emerged as an effective procedure to treat resistant hypertension by blocking the sympathetic nervous system. The medical device industry has developed various catheters in an effort to achieve better denervation in the absence of available testing to document adequate denervation. By adding a sham control group to the study design, researchers found that the results of the Renal Denervation in Patients With Uncontrolled Hypertension study (SYMPLICITY HTN-3) showed that renal denervation was not superior to placebo in decreasing systolic blood pressure. Although SYMPLICITY HTN-3 successfully addressed many issues that might have biased the previously published data, incomplete denervation caused by limited operator experience, catheter design, and the radiofrequency ablation technology may have accounted for the discrepancy of the results. This, along with differences in the study design and population, should direct future renal denervation studies. This article reviews the available literature and proposes future directions for renal denervation studies. It also provides a detailed comparison of the available catheters and their respective clinical data.

Autonomic modulation for the management of patients with chronic heart failure.

Dysregulation of the autonomic nervous system in heart failure (HF) has received considerable attention during the past 3 decades, largely because of the well-recognized association between increased sympathetic activity and the elaboration of biologically active molecules, collectively referred to as neurohormones, that help to maintain cardiovascular homeostasis through increased volume expansion, peripheral arterial vasoconstriction, and increased myocardial contractility. However, high and sustained levels of these biologically active molecules (eg, norepinephrine, angiotensin II, aldosterone) are overtly toxic to the heart and circulation.1 These and other insights have led to the clinical use of neurohormonal antagonists, such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, aldosterone antagonists, and β-blockers to treat patients with HF with a reduced left ventricular ejection fraction (LVEF).1 The effectiveness of these pharmacological agents is predominantly because of their ability to directly antagonize the deleterious effects of excessive sympathetic and renin–angiotensin activation. However, the current guideline-directed medical therapy (GDMT) in patients with HF fails to completely restore normal autonomic balance disrupted as a part of HF pathophysiology. During the last decade, a novel approach has generated widespread interest: modulation of the autonomic nervous system as a result of either a one-time intervention (eg, denervation) or of ongoing active therapy (eg, electric stimulation) as a means of further diminishing the sympathovagal imbalance that develops in HF.2,3 Of note, therapeutic neuromodulation with device-based therapies, either with spinal cord stimulation (SCS) or vagal stimulation (VS), has been used safely in patients with chronic pain, epilepsy, and depression, since the 1980s. As noted above, HF with a reduced LVEF is associated with sustained activation of the sympathetic nervous system that is accompanied by a withdrawal of parasympathetic tone. Impaired arterial baroreflexes have been proposed as an important mechanism that contributes to the sympathovagal imbalance present in HF4 …

The significance of muscle echo intensity on ultrasound for focal neuropathy: The median- to ulnar-innervated muscle echo intensity ratio in carpal tunnel syndrome

ObjectiveThe objective of this study was to investigate the usefulness of muscle ultrasound for evaluating muscle changes caused by denervation in carpal tunnel syndrome (CTS), which is a focal neuropathy. MethodsThe mean and standard deviation (SD) of echo intensity (EI) in the thenar and hypothenar muscles were calculated in 35 patients with CTS and 11 healthy subjects. Patients were assigned to three subgroups based on CTS severity as determined by electrodiagnostic tests. The ratio of thenar muscle pixel brightness to hypothenar muscle pixel brightness was used in statistical analyses. The ratio of mean pixel brightness was termed the EI ratio, and the ratio of the SD of pixel brightness was termed the inhomogeneity ratio. ResultsBoth the EI ratio and the inhomogeneity ratio were significantly higher in the patient group than in the control group. In a comparison of the three patient subgroups, the severe group showed significant differences in both the EI and inhomogeneity ratios compared to the other two groups. Subjects with denervation potential in the abductor pollicis brevis (APB) had higher EI and inhomogeneity ratios than subjects without denervation potential in the APB. ConclusionThe EI ratio and inhomogeneity ratio are useful variables with which to evaluate disease severity and the presence of denervation in patients with CTS. SignificanceMuscle ultrasound has clinical significance in the detection of muscle changes that result from neuropathy.

Renal sympathetic denervation in patients with implantable cardioverter-defibrillator and electrical storm

BackgroundImplantable cardioverter-defibrillators (ICDs) are usually indicated for patients with malignant arrhythmias considered as high risk. Sympathetic hyperactivity plays a critical role in the development, maintenance, and worsening of ventricular arrhythmias. New treatment options in this population represent a clinical necessity. This study's objective was to report the outcomes of patients with ICDs and electrical storm submitted to renal sympathetic denervation for arrhythmia control. MethodsEight patients with ICDs admitted for electrical storm refractory to optimal medical therapy underwent renal sympathetic denervation. Underlying diseases included Chagas disease (n=6), non-ischemic dilated cardiomyopathy (n=1), and ischemic cardiomyopathy (n=1). Information on the number of episodes of ventricular tachycardia/ventricular fibrillation and antitachycardia therapies in the week before the procedure and 30 days after treatment were obtained through interrogation of the ICDs. ResultsThe median numbers of episodes of ventricular tachycardia/ventricular fibrillation, antitachycardia pacing, and shocks in the week before renal sympathetic denervation were 29 (9 to 106), 23 (2 to 94), and 7.5 (1 to 88), and significantly reduced to 0 (0 to 12), 0 (0 to 30), and 0 (0 to 1), respectively, 1 month after the procedure (p=0.002; p=0.01; p=0.003, respectively). No patients died during follow-up. There were no major complications related to the procedure. ConclusionsIn patients with ICDs and electrical storm refractory to optimal medical treatment, renal sympathetic denervation significantly reduced arrhythmia load and, consequently, antitachycardia pacing and shocks. Randomized clinical trials in the context of renal sympathetic denervation to control refractory cardiac arrhythmias are needed to further support these findings.

Incidence of renal artery stenosis after renal denervation in patients with resistant arterial hypertension

Catheter-based ablation of nerves in the adventitia of renal arteries (renal artery denervation [RAD]) using radiofrequency energy can reduce blood pressure (BP) in patients with resistant arterial hypertension (RAH). Occurrence of renal artery stenosis after RAD is still an important concern. We systematically investigated the renal artery anatomy using magnetic resonance imaging (MRI) or computed tomography (CT) angiography in a consecutive series of patients 6 months after RAD. Patients with RAH were treated by RAD after exclusion of secondary causes of hypertension. RAH was defined by a mean systolic office BP >160 mm Hg. Renal artery imaging was performed 6 months after RAD by MRI angiography. In case of any contraindication for MRI, a CT angiography was performed. The primary end point was the incidence of significant renal artery stenosis (‡70% lumen diameter reduction). RAD was performed in 76 patients, and evaluation of renal artery anatomy by MRI (n [ 66; 87%) or CT angiography (n [ 10; 13%) was performed in all patients 6 months after RAD. We found no renal artery stenosis but 2 cases of new nonsignificant stenosis (50% TO 69% lumen diameter reduction). In responders, mean systolic office BP reduction was L30 mm Hg (p <0.001) and mean systolic 24-hour BP reduction was L18 mm Hg (p <0.001). In conclusion, the incidence of significant renal artery stenosis 6 months after RAD seems to be very low. However, late-onset development of nonsignificant renal artery narrowing cannot be excluded in some patients and should be anticipated in the case of RAH relapse or worsening of renal function after successful

12-Month Blood Pressure Results of Catheter-Based Renal Artery Denervation for Resistant Hypertension: The SYMPLICITY HTN-3 Trial

BackgroundResults of the SYMPLICITY HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension) trial confirmed the safety but not the efficacy of renal denervation for treatment-resistant hypertension at 6 months post procedure. ObjectivesThis study sought to analyze the 12-month SYMPLICITY HTN-3 results for the original denervation group, the sham subjects who underwent denervation after the 6-month endpoint (crossover group), and the sham subjects who did not undergo denervation after 6 months (non-crossover group). MethodsEligible subjects were randomized 2:1 to denervation or sham procedure. Subjects were unblinded to their treatment group after the 6-month primary endpoint was ascertained; subjects in the sham group meeting eligibility requirements could undergo denervation. Change in blood pressure (BP) at 12 months post randomization (6 months for crossover subjects) was analyzed. ResultsThe 12-month follow-up was available for 319 of 361 denervation subjects and 48 of 101 non-crossover subjects; 6-month denervation follow-up was available for 93 of 101 crossover subjects. In denervation subjects, the 12-month office systolic BP (SBP) change was greater than that observed at 6 months (−15.5 ± 24.1 mm Hg vs. −18.9 ± 25.4 mm Hg, respectively; p = 0.025), but the 24-h SBP change was not significantly different at 12 months (p = 0.229). The non-crossover group office SBP decreased by −32.9 ± 28.1 mm Hg at 6 months, but this response regressed to −21.4 ± 19.9 mm Hg (p = 0.01) at 12 months, increasing to 11.5 ± 29.8 mm Hg. ConclusionsThese data support no further reduction in office or ambulatory BP after 1-year follow-up. Loss of BP reduction in the non-crossover group may reflect decreased medication adherence or other related factors. (Renal Denervation in Patients With Uncontrolled Hypertension [SYMPLICITY HTN-3]; NCT01418261)

Randomized sham-controlled trial of renal sympathetic denervation in mild resistant hypertension.

Few data are available with regard to the effectiveness of renal sympathetic denervation in patients with resistant hypertension yet only mildly elevated blood pressure (BP). Patients with resistant hypertension and slightly elevated BP (day-time systolic pressure, 135-149 and diastolic pressure, 90-94 mm Hg on 24-hour ambulatory measurement) were randomized in a 1:1 ratio to renal sympathetic denervation with the Symplicity Flex Catheter (Medtronic) or an invasive sham procedure. The primary efficacy end point was the change in 24-hour systolic BP at 6 months between groups in the intention to treat population. A total of 71 patients underwent randomization. Baseline day-time systolic BP was 144.4±4.8 mm Hg in patients assigned to denervation and 143.0±4.7 mm Hg in patients randomized to the sham procedure. The mean change in 24-hour systolic BP in the intention to treat cohort at 6 months was -7.0 mm Hg (95% confidence interval, -10.8 to -3.2) for patients undergoing denervation and -3.5 mm Hg (95% confidence interval, -6.7 to -0.2) in the sham group (P=0.15). In the per protocol population, the change in 24-hour systolic BP at 6 months was -8.3 mm Hg (95% confidence interval, -11.7 to -5.0) for patients undergoing denervation and -3.5 mm Hg (95% confidence interval, -6.8 to -0.2) in the sham group (P=0.042). In patients with mild resistant hypertension, renal sympathetic denervation failed to show a significant reduction in the primary end point of 24-hour systolic BP at 6 months between groups in the intention to treat analysis. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01656096.

Frequency of Renal Artery Stenosis After Renal Denervation in Patients With Resistant Arterial Hypertension

Catheter-based ablation of nerves in the adventitia of renal arteries (renal artery denervation [RAD]) using radiofrequency energy can reduce blood pressure (BP) in patients with resistant arterial hypertension (RAH). Occurrence of renal artery stenosis after RAD is still an important concern. We systematically investigated the renal artery anatomy using magnetic resonance imaging (MRI) or computed tomography (CT) angiography in a consecutive series of patients 6months after RAD. Patients with RAH were treated by RAD after exclusion of secondary causes of hypertension. RAH was defined by a mean systolic office BP >160mm Hg. Renal artery imaging was performed 6months after RAD by MRI angiography. In case of any contraindication for MRI, a CT angiography was performed. The primary end point was the incidence of significant renal artery stenosis (≥70% lumen diameter reduction). RAD was performed in 76 patients, and evaluation of renal artery anatomy by MRI (n= 66; 87%) or CT angiography (n= 10; 13%) was performed in all patients 6months after RAD. We found no renal artery stenosis but 2 cases of new nonsignificant stenosis (50% TO 69% lumen diameter reduction). In responders, mean systolic office BP reduction was-30mm Hg (p <0.001) and mean systolic 24-hour BP reduction was-18mm Hg (p <0.001). In conclusion, the incidence of significant renal artery stenosis 6months after RAD seems to be very low. However, late-onset development of nonsignificant renal artery narrowing cannot be excluded in some patients and should be anticipated in the case of RAH relapse or worsening of renal function after successful RAD.

Cardiorenal syndrome in chronic kidney disease.

The purpose of this study is to review current perspectives regarding the pathogenesis of cardiorenal syndrome (CRS) in chronic kidney disease (CKD), and current treatment guidelines for this condition. The pathophysiological mechanisms underlying the development of CRS in CKD include neurohumoral, haemodynamic and CKD-related mechanisms. Recent evidence suggests that sympathetic nerve activity plays a role in CRS, but the SYMPLICITY HTN-3 trial failed to show a reduction of blood pressure after catheter-based renal denervation in patients with resistant hypertension. Kidney injury in patients with heart failure was previously considered to result from arterial underfilling due to low cardiac output, but the role of renal venous hypertension in this process has also recently been investigated. It would be useful to develop a reliable treatment option for CRS due to haemodynamic mechanism other than volume control using diuretics. Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone that has recently been identified as a CKD-related factor affecting CRS. FGF23 treatment has both advantages and disadvantages in terms of CRS progression. Multiple disorders underlie the development of CRS. Current treatment options include renin-angiotensin system blockade and volume control, but remain limited. A multidisciplinary approach is required to prevent CRS, including renal sympathetic denervation, treatment of renal venous hypertension and FGF23 treatment.

First report of the Global SYMPLICITY Registry on the effect of renal artery denervation in patients with uncontrolled hypertension.

This study aimed to assess the safety and effectiveness of renal denervation using the Symplicity system in real-world patients with uncontrolled hypertension (NCT01534299). The Global SYMPLICITY Registry is a prospective, open-label, multicenter registry. Office and 24-hour ambulatory blood pressures (BPs) were measured. Change from baseline to 6 months was analyzed for all patients and for subgroups based on baseline office systolic BP, diabetic status, and renal function; a cohort with severe hypertension (office systolic pressure, ≥160 mm Hg; 24-hour systolic pressure, ≥135 mm Hg; and ≥3 antihypertensive medication classes) was also included. The analysis included protocol-defined safety events. Six-month outcomes for 998 patients, including 323 in the severe hypertension cohort, are reported. Mean baseline office systolic BP was 163.5±24.0 mm Hg for all patients and 179.3±16.5 mm Hg for the severe cohort; the corresponding baseline 24-hour mean systolic BPs were 151.5±17.0 and 159.0±15.6 mm Hg. At 6 months, the changes in office and 24-hour systolic BPs were -11.6±25.3 and -6.6±18.0 mm Hg for all patients (P<0.001 for both) and -20.3±22.8 and -8.9±16.9 mm Hg for those with severe hypertension (P<0.001 for both). Renal denervation was associated with low rates of adverse events. After the procedure through 6 months, there was 1 new renal artery stenosis >70% and 5 cases of hospitalization for a hypertensive emergency. In clinical practice, renal denervation resulted in significant reductions in office and 24-hour BPs with a favorable safety profile. Greater BP-lowering effects occurred in patients with higher baseline pressures. URL: www.clinicaltrials.gov. Unique identifier: NCT01534299.