Benefit Of Renal Denervation Research Articles

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.

Benefits of renal denervation in HFrEF

Benefits of renal denervation in HFrEF

Salt Diet Influences Endothelin‐1 Signaling in Renal Sensory Nerves

Renal denervation is an effective anti‐hypertensive treatment in both humans and many animal models. However, it is unclear if the benefits of renal denervation are due to severing of the efferent (motor) nerves, afferent (sensory) nerves, or both. Recently, we reported that total renal denervation lowered blood pressure and global sympathetic tone in a model of endothelin B receptor (ETB‐R) deficiency without affecting renal excretory function or sodium balance suggesting a role for the afferent nerves in mediating hypertension and sympathetic tone in this model. High salt diet and endothelin‐1 signaling sensitize afferent activity, but the long‐term consequences and mechanisms of afferent sensitization are still relatively unknown. Thus we hypothesized that changes in salt diet would alter the gene expression profiles in renal afferent nerves following a high or low salt diet or endothelin receptor antagonist treatment. We isolated dorsal root ganglia (DRG) that contain the cell bodies of renal afferent nerves from Sprague‐Dawley rats fed either normal salt (NS, 0.49% NaCl), low salt (LS, 0.04% NaCl), or high salt (HS, 4.0% NaCl) for three weeks, or normal salt with 10 mg/kg/d ABT‐627 (ETA‐R antagonist) or 30 mg/kg/d A‐192621 (ETB‐R antagonist) for one week for qRT‐PCR analysis. Rats fed HS diet had significantly elevated expression of brain‐derived neurotrophic factor compared to NS (5.9 ± 1.8 relative to NS; p=0.04, n=3–4/group) indicating that HS diet activates renal afferent nerves as has been previously reported. Animals fed LS diet were not significantly different than NS. Neither salt diet had a significant effect on endothelin‐1 expression in DRG. Surprisingly, both LS and HS diets decreased the expression of both ETA‐R (0.7 ± 0.01 relative to NS p=0.1 and 0.4 ± 0.2 relative to NS p=0.04; respectively) and ETB‐R (0.5 ± 0.03 relative to NS p<0.001; and 0.5 ± 0.1 relative to NS p<0.001; respectively). Antagonism of ETA‐R resulted in a 2.0 ± 0.3 fold increase in endothelin‐1 expression in DRG compared to NS (p=0.02), while ETB‐R blockade had no effect (p=0.99) compared to NS, suggesting that ETA‐R activity may suppress endothelin‐1 expression in renal afferent nerves. These data suggest that salt diet influences activity of renal afferent nerves and that endothelin‐1 signaling in afferent nerves may be important modulators of activity.Support or Funding InformationT32HL007457 to BKB; K99HL127178 to JSS; and P01HL136267 to DMPThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Renal denervation in the treatment of resistant hypertension: Dead, alive or surviving?

Hypertension is one of the most common chronic clinical problems encountered by physicians. The prevalence of resistant hypertension is estimated at 9% in the US. Patients with resistant hypertension have been shown to be at higher risk for adverse cardiovascular events, hence the need for greater efforts in improving the treatment of hypertension. The renal sympathetic nerves play an important role in the development of hypertension, mediated via sodium and water retention, increased renin release and alterations in renal blood flow. The proximity of the afferent and efferent renal sympathetic nerves to the adventitia of the renal arteries suggested the feasibility of an endovascular, selective, minimally invasive approach to renal denervation; a potential treatment option for resistant hypertension. While the RAPID, Reduce-HTN, EnligHTN, DENERHTN and Symplicity HTN-1 and -2 studies showed significant benefit of renal denervation in the treatment of resistant hypertension, the results of Oslo RDN, Prague-15 and Symplicity HTN-3 were not so favorable. Future well-designed clinical trials are needed to ascertain the benefits or otherwise of renal denervation in treatment-resistant hypertension.

What is the benefit of renal denervation?

What is the benefit of renal denervation?

Renal Denervation.

Sympathetic nervous system over-activity is closely linked with elevation of systemic blood pressure. Both animal and human studies suggest renal sympathetic nerves play an important role in this respect. Historically, modulation of sympathetic activity has been used to treat hypertension. More recently, catheter based renal sympathetic denervation was introduced for the management of treatment resistant hypertension. Sound physiological principles and surgical precedent underpin renal denervation as a therapy for treatment of resistant hypertension. Encouraging results of early studies led to a widespread adoption of the procedure for management of this condition. Subsequently a sham controlled randomised controlled study failed to confirm the benefit of renal denervation leading to a halt in its use in most countries in the world. However, critical analysis of the sham-controlled study indicates a number of flaws. A number of lessons have been learnt from this and other studies which need to be applied in future trials to ascertain the actual role of renal denervation in the management of treatment resistant hypertension before further implementation. This chapter deals with all these issues in detail.

Top Stories of 2014

Dear Readers,This has been another exciting year for cardiology, and it's time again to provide you with our top stories of the year, chosen by our

Is isolated systolic hypertension an indication for renal denervation?

Ewen et al. recently reported in the journal Hypertension that they investigated, for the first time, the effect of renal denervation on blood pressure in 63 patients with isolated systolic hypertension (Ewen et al., 2014). The authors concluded that renal denervation reduced office and ambulatory blood pressure in patients with isolated systolic hypertension (Ewen et al., 2014). However, this conclusion may not be drawn, as renal denervation may not decrease ambulatory blood pressure in these patients. The potential risk of renal denervation may overweigh its benefit in patients with isolated systolic hypertension. Therefore, adjusted drug treatment may be recommended to these patients before renal denervation. Ambulatory blood pressure monitoring is the gold standard to diagnose true hypertension and removes the white coat effect (Hermida et al., 2013). Ambulatory blood pressure is superior to office blood pressure in predicting cardiovascular events (Staessen et al., 1999) and mortality (Dolan et al., 2005). The 24-h ambulatory systolic blood pressure in these 63 patients in Ewen et al.'s report decreased by 8 ± 8 and 7 ± 8 mm Hg at 6 and 12 months respectively after renal denervation. However, this study lacked a control group as the authors pointed out as a limitation. It has been reported that the sham procedure reduced 24-h ambulatory systolic blood pressure by 5 ± 15 mm Hg at 6 months (Bhatt et al., 2014). Therefore, compared with the sham procedure, renal denervation may not decrease ambulatory blood pressure in those patients with isolated systolic hypertension. Consequently, the risk posed to patients with isolated systolic hypertension by renal denervation may overweigh the minimal benefit of renal denervation via lowering blood pressure. For example, renal artery stenosis after renal denervation is of concern. The renal artery stenosis rate in the Symplicity HTN trials (N = 45, 106, and 535 for the Symplicity HTN-1, HTN-2, and HTN-3 trials, respectively) ranges from 0.3 to 2.2% (Krum et al., 2009; Esler et al., 2010; Bhatt et al., 2014). However, more and more studies with a smaller sample size (Worthley et al., 2013; Versaci et al., 2014) and case reports (Kaltenbach et al., 2012; Vonend et al., 2012; Aguila et al., 2014; Bacaksiz et al., 2014; Chandra et al., 2014; Pucci et al., 2014) showed relatively higher rates of development or progression of renal artery stenosis after renal denervation. Ewen et al. did not observe any hemodynamically significant renal artery stenosis in these 63 patients with isolated systolic hypertension within 12 months (Ewen et al., 2014). However, ultrasonography, which was used by the authors, has limitations in detecting renal artery stenosis (Zhang et al., 2009; Lao et al., 2011). Renal denervation is regarded as a last resort for patients with resistant hypertension (Persu et al., 2012). It is reported that about 9% of adults with hypertension suffer from resistant hypertension (Persell, 2011), which is often defined as elevated blood pressure despite treatment with at least 3 antihypertensive agents including a diuretic at maximal tolerated or highest recommended doses (Bohm et al., 2014). The prevalence of resistant hypertension is likely over-estimated due to drug non-adherence. For example, blood pressure in 20 of 65 patients with resistant hypertension was normalized after witnessed intake of antihypertensive drugs (Fadl Elmula et al., 2014). Resistant hypertension has been classified as “true” resistant hypertension if blood pressure is still elevated after witnessed intake of antihypertensive drugs (Fadl Elmula et al., 2014). Blood pressure in some patients with “true” resistant hypertension could be controlled by adjusted drug treatment. For example, Fadl Elmula et al. reported that adjusted drug treatment significantly decreased ambulatory systolic blood pressure from 152 ± 12 mm Hg at baseline to 133 ± 11 mm Hg at 6 months in 10 patients with “true” resistant hypertension (Fadl Elmula et al., 2014). In addition, adjusted drug treatment lowered ambulatory systolic blood pressure to below 135 mm Hg in 7 of these 10 patients with “true” resistant hypertension (Fadl Elmula et al., 2014). Therefore, patients with isolated systolic hypertension may be offered with adjusted drug treatment before being offered with renal denervation. In summary, renal denervation may not decrease ambulatory blood pressure in patients with isolated systolic hypertension. Adjusted drug treatment may be recommended to these patients before renal denervation, as the risk might overweigh the benefit of renal denervation in these patients.

Renal Denervation Prevents Stroke and Brain Injury via Attenuation of Oxidative Stress in Hypertensive Rats

BackgroundAlthough renal denervation (RD) is shown to reduce blood pressure significantly in patients with resistant hypertension, the benefit of RD in prevention of stroke is unknown. We hypothesized that RD can prevent the incidence of stroke and brain injury in hypertensive rats beyond blood pressure lowering.Methods and ResultsHigh‐salt‐loaded, stroke‐prone, spontaneously hypertensive rats (SHRSP) were divided into 4 groups: (1) control; (2) sham operation; (3) bilateral RD; and (4) hydralazine administration to examine the effect of RD on stroke and brain injury of SHRSP. RD significantly reduced the onset of neurological deficit and death in SHRSP, and this protection against stroke by RD was associated with the increase in cerebral blood flow (CBF), the suppression of blood–brain barrier disruption, the limitation of white matter (WM) lesions, and the attenuation of macrophage infiltration and activated microglia. Furthermore, RD significantly attenuated brain oxidative stress, and NADPH oxidase subunits, P67 and Rac1 in SHRSP. On the other hand, hydralazine, with similar blood pressure lowering to RD, did not significantly suppress the onset of stroke and brain injury in SHRSP. Furthermore, RD prevented cardiac remodeling and vascular endothelial impairment in SHRSP.ConclusionsOur present work provided the first experimental evidence that RD can prevent hypertensive stroke and brain injury, beyond blood pressure lowering, thereby highlighting RD as a promising therapeutic strategy for stroke as well as 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.

What are the benefits of renal denervation in patients with resistant hypertension?

Systemic arterial hypertension is one of the most important public health issues, affecting more than one-quarter of the adult population in industrialized countries [1]. It is a major risk factor for cardiovascular disease morbidity and mortality [2,3]. In most patients, hypertension can be effectively managed by a combination of lifestyle interventions and medication [4]. However, a significant portion of patients treated for hypertension are resistant to therapy. Conventionally, resistant hypertension is defined as persistent elevation of blood pressure above goal levels despite the use of at least three hypertensive agents from different classes, including a diuretic, in optimal doses [5]. Current prevalence estimates suggest that 10–30% of patients with hypertension may be resistant to drug therapy [6]. Renal sympathetic overactivity seems to play a crucial role in the development of arterial hypertension and resistance to treatment. Activation of efferent renal sympathetic nerve fibers results in an increased renin secretion rate, increased renal vasoconstriction and enhanced sodium and water retention [7]. In addition, afferent sympathetic activation from the kidneys to the CNS, seems to enhance sympathetic nerve discharge itself again, leading to a vicious circle in the development of arterial hypertension and cardiovascular morbidity [8]. Both effects, the activation of efferent renal sympathetic nerve fibers as well as the afferent ‘feedback’ from the kidneys seem to play a crucial role in the pathogenesis and maintenance of arterial hypertension. The idea of treating arterial hypertension by targeting the autonomic nervous system is decades old. In the predrug era, treatment of malignant hypertension was limited to surgical approaches, such as nephrectomy and surgical lysis of the autonomic nerves. Nonselective surgical sympathectomy (thoracolumbar splanchnicectomy), the so-called Smithwick intervention,

Renal Denervation: A Potential New Treatment for Severe Hypertension

Hypertension is a leading cause of cardiovascular morbidity and mortality. Drug-resistant hypertension remains common despite the availability of several classes of effective antihypertensive agents. Sympathetic hyperactivity has long been recognized as a major contributor to resistant hypertension, but radical sympathectomy was abandoned several decades ago due to its significant side effects. The newly developed, minimally invasive, catheter-based renal sympathetic denervation procedure has been shown in recent trials to produce impressive blood pressure reductions and a favorable safety profile in drug-resistant hypertension. Although the long-term efficacy and safety of renal denervation remains to be determined, emerging data suggest that the benefits of renal denervation may extend beyond blood pressure control.

Renal Sympathetic Denervation for Treatment of Hypertension.

OPINION STATEMENT: Sympathetic nervous system activation of the heart, kidney and peripheral vasculature increases cardiac output, fluid retention and vascular resistance and plays an important role in acute and chronic BP elevation. Renal sympathetic denervation via a percutaneous radiofrequency catheter based approach is a safe and effective procedure that lowers BP in patients with resistant hypertension. Exploratory studies in patients with resistant hypertension and a variety of comorbidities, including insulin resistance/metabolic syndrome, obstructive sleep apnea and the polycystic ovary syndrome, have shown benefit of renal denervation in attenuating the severity of the comorbid conditions, as well as reducing BP. However, more studies are needed to further address the long term effects of renal denervation and its safety and effectiveness in other disease states such as congestive heart failure.

Autonomic Dysfunction in Heart Failure and Renal Disease

EDITORIAL article Front. Physiol., 26 June 2012Sec. Integrative Physiology Volume 3 - 2012 | https://doi.org/10.3389/fphys.2012.00219