Percutaneous Catheter-based Renal Denervation Research Articles

Laparoscopic Renal Denervation System for Treating Resistant Hypertension: Overcoming Limitations of Catheter-Based Approaches.

In a pivotal clinical trial, the percutaneous catheter-based renal denervation system developed to treat resistant hypertension did not show effectiveness in reducing blood pressure because of its fundamental limitation to ablate deeper nerves present around the renal artery. We propose a new renal denervation strategy called laparoscopicdenervation system (LDS) based-on laparoscopy procedure to ablate the renal nerves completely but inhibit the thermal arterial damage.The system has flexible electrodes to bend around the arterial wall to ablate nervesThe simulation study using validated in-silico models evaluated the heat distributionon the outer arterial wall,and an acute animal study (swine model) was conducted to demonstrate the feasibility of LDS in vivo. The simulation studyconfirmedthat LDS could localize the heat distributionbetween the electrode and the outer arterial wall. In the animal study, we could maximize nerve denervation by the localizing ablation energy within the renal nerves and achieve nerve denaturationand decrease in neural density by 20.78% (P < 0.001), while maintaining a constant tip temperature of 65 °C for the duration of 70 s treatment. The study confirmed intact lumen artery through histological analysis and acute reduction in systolic blood pressure by 9.55 mmHg (p < 0.001) Conclusion: The LDS presented here has potential to effectively and safely ablate the renal nerves, independent of anatomical variation and nerve distribution, to control hypertension in real clinical conditions. LDS approach is innovative, inventive, and presents a novel technique totreat hypertension.

Catheter-based renal denervation as therapy for chronic severe kidney-related pain.

Loin pain haematuria syndrome (LPHS) and autosomal dominant polycystic kidney disease (ADPKD) are the most important non-urological conditions to cause chronic severe kidney-related pain. Multidisciplinary programmes and surgical methods have shown inconsistent results with respect to pain reduction. Percutaneous catheter-based renal denervation (RDN) could be a less invasive treatment option for these patients. Our aim was to explore the change in perceived pain and use of analgesic medication from baseline to 3, 6 and 12 months after RDN. Patients with LPHS or ADPKD, who experienced kidney-related pain ≥3 months with a visual analogue scale (VAS) score ≥ 50/100 could be included. Percutaneous RDN was performed with a single-electrode radiofrequency ablation catheter. RDN was performed in 11 patients (6 with LPHS and 5 with ADPKD). Perceived pain declined in the whole group by 23 mm (P = 0.012 for the total group). In patients with LPHS and ADPKD, the median daily defined dosage of analgesic medication decreased from 1.6 [interquartile range (IQR) 0.7-2.3] and 1.4 (IQR 0.0-7.4) at baseline to 0.3 (IQR 0.0-1.9; P = 0.138) and 0.0 (IQR 0.0-0.8; P = 0.285) at 12 months, respectively. Mean estimated glomerular filtration rate decreased in the whole group by 5.4 mL/min/1.73 m2 at 6 months compared with baseline (P = 0.163). These results suggest that percutaneous catheter-based RDN reduces pain complaints and the use of analgesic medication in patients with LPHS or ADPKD. The present results can serve as the rationale for a larger, preferably randomized (sham) controlled study.

Renal artery sympathetic nerve radiofrequency denervation.

Arterial hypertension is one of the most common chronic diseases in the western world, affecting more than 25% of the adult population. The aim of this study was to assess changes in arterial blood pressure (BP) levels in hypertensive patients, after ablation of nerve terminals in renal arteries, using radiofrequency energy during 24 months of follow-up. Thirty-two patients with diagnosed resistant hypertension (20 men and 12 women) underwent percutaneous catheter-based renal denervation of nerve terminals in renal artery walls. Mean BP value before ablation was [mm Hg]: systolic 174.92, diastolic 99.73 and pulse pressure 75.19. After procedure reduction value of BP was reported [mm Hg]: systolic 146.78; diastolic 87.14, pulse pressure 59.64 at 24-month follow-up (p < 0.05 for all). 30% of patients had systolic BP ≤ 140 mm Hg, 67% had diastolic BP ≤ 90 mm Hg, and optimum BP values ≤ 140/90 mm Hg were observed in 30% of patients. In our cohort of patients, percutaneous renal artery ablation procedure effectively reduces systolic, diastolic BP and pulse pressure. No adverse events during 24 months of follow-up were noted. These results were comparable with available data from SIMPLICITY I and II trials.

Catheter-based renal denervation reduces atrial nerve sprouting and complexity of atrial fibrillation in goats.

Atrial fibrillation (AF) leads to structural and neural remodeling in the atrium, which enhances AF complexity and perpetuation. Renal denervation (RDN) can reduce renal and whole-body sympathetic activity. Aim of this study was to determine the effect of sympathetic nervous system modulation by RDN on atrial arrhythmogenesis. Eighteen goats were instrumented with an atrial endocardial pacemaker lead and a burst pacemaker. Percutaneous catheter-based RDN was performed in 8 goats (RDN-AF). Ten goats undergoing a sham procedure served as control (SHAM-AF). AF was induced and maintained by burst pacing for 6 weeks. High-resolution mapping was used to record epicardial conduction patterns of the right and left atrium. RDN reduced tyrosine hydroxylase-positive sympathetic nerve staining and resulted in lower transcardiac norepinephrine levels. This was associated with reduced expression of nerve growth factor-β, indicating less atrial nerve sprouting. Atrial endomysial fibrosis content was lower and myocyte diameter was smaller in RDN-AF. Median conduction velocity was higher (75 ± 9 versus 65 ± 10 cm/s, P = 0.02), and AF cycle length was shorter in RDN-AF compared with SHAM-AF. Left atrial AF complexity (4.8 ± 0.8 fibrillation waves/AF cycle length versus 8.5 ± 0.8 waves/AF cycle length, P = 0.001) and incidence of breakthroughs (2.0 ± 0.3 versus 4.3 ± 0.5 waves/AF cycle length, P = 0.059) were lower in RDN-AF compared with SHAM-AF. Blood pressure was normal and not significantly different between the groups. RDN reduces atrial sympathetic nerve sprouting, structural alterations, and AF complexity in goats with persistent AF, independent of changes in blood pressure.

Denervation of nerve terminals in renal arteries: one-year follow-up of interventional treatment of arterial hypertension

Arterial hypertension is the most common cardiovascular system disease, affecting nearly one billion people worldwide. Despite the widespread use of antihypertensive medications, in some groups of patients an optimal blood pressure (BP) cannot be achieved. To assess BP reduction in patients with resistant hypertension after a catheter-based renal sympathetic denervation procedure and to report vascular and kidney safety in one-year follow-up. Twenty eight patients with diagnosed resistant hypertension (median age 52.02 years, range 42-72) underwent percutaneous catheter-based renal denervation of nerve terminals in renal arteries. Arterial angiography and procedure of ablation was performed by Symplicity catheters and generator provided by Ardian (currently Medtronic Inc., USA). Mean BP value before ablation was [mm Hg]: systolic 176.6, diastolic 100.28 and pulse pressure 73.4. After the procedure, reductions in the value of BP were reported [mm Hg]: systolic 154.8/152.54; diastolic 90.2/89.8, pulse pressure 64.66/62.73, respectively in nine-month and one-year follow-up. All results were statistically significant. No complications during one year observation were observed. Percutaneous renal artery ablation procedure effectively reduces systolic BP, diastolic BP, and pulse pressure. No vascular or renal complications in any of the patients were observed. The results of a Polish research group showed no significant differences compared to the results obtained in the international studies Symplicity I and Symplicity II.

Stenting for atherosclerotic renal-artery stenosis: A blind alley?

Renal-artery stenosis, a common disease among persons older than 65 years,may result in hypertension, ischemic nephropathy, and multiple long-term complications [1]. Early studies [2] suggested that renal-artery angioplasty or stentingmay result in significant reductions in systolic blood pressure. However, the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial [3] recently presented a definitive test of the usefulness of renal-artery stents for moderately severe renalartery stenosis and made a conclusion that renal-artery stenting is no better than medical therapy alone in preventing clinical events. It seems that stenting for renal-artery stenosis after years of its clinical use hits a blind alley. However, pathophysiological changes after stenting include not only improvement in the diameter of the stenotic renal artery but also the tissues of and around the artery, particularly the sympathetic nerve fibers which lie in the adventitia of the renal artery (Fig.1). A recent research [4] demonstrated that balloon angioplasty can reduce the number of sympathetic nerve fibers of the renal artery. So this may be more than just a theoretical consideration. Renal-artery stenosis is characterized not onlybyactivationof the renin–angiotensin system, but also byheightened sympathetic drive [5] which contributes to the pathophysiology of numerous chronic cardiovascular diseases such as essential hypertension, heart failure, chronic kidney disease, diabetes and so on. Nowadays percutaneous catheter-based renal denervation (RDN) is emerging as a new, effective and safe approach to achieve sustained blood pressure reduction in patients with resistant hypertension which can decrease sympathetic activity by interrupting the afferent and efferent renal sympathetic nervous fibers located in the adventitia of the renal arteries by delivery of radiofrequency energy. Herein, we hypothesize that RDN on patients with prior renal stents may enhance the damages of renal sympathetic nervous fibers and reduce the sympathetic activities to a much lower level. However, renal-artery stenosis and prior renal stents are considered a contraindication in routine clinical practice of RDN due to technological unavailability and a worry of deterioration of stenosis. Nevertheless, one case report [6] explored and demonstrated the feasibility and potential effectiveness of the combination of RDN and renal stenting. What's more, a recent small animal study [7] proved that vascular brachytherapy which has been approved for the treatment of in-stent restenosis can also cause renal sympathetic nerve fibrosis while avoiding significant damage to the renal artery. All theseexplorationsmaybreak new ground of therapy with renal-artery stenosis.

Renal Denervation for Hypertension

Hypertension is the leading cause of mortality worldwide. Effective therapies are needed for resistant hypertension, a common condition characterized by inadequate blood pressure control despite 3 or more medications, which is associated with increased cardiovascular mortality. Percutaneous catheter-based renal denervation is a promising new treatment offering the potential to improve blood pressure control, reduce cardiovascular risk, and target end-organ damage in patients with resistant hypertension. Initial studies have demonstrated procedural safety and effectiveness in blood pressure reduction up to 2 years after procedure. Large randomized control trials are necessary and currently underway to define further the role of renal denervation and long-term consequences in the treatment of resistant hypertension.

Sympathetic Hyperactivity in Chronic Kidney Disease: Pathophysiology and (New) Treatment Options

Abundant evidence shows that chronic kidney disease (CKD) is a disease state characterized by increased sympathetic activation. Kidney injury (ischemia) plays a central role in this pathogenesis. Sympathetic excitation is associated with an increased risk of cardiovascular morbidity and mortality. Several pharmacologic strategies are developed to decrease sympathetic activity. However, these medications have limitations. Percutaneous catheter-based renal denervation has the potential to become a new treatment option for CKD. This current report focuses on the effects of sympathetic hyperactivity in CKD, and gives an overview in experimental as well as clinical evidence for a central role of the kidneys in the pathophysiology of sympathetic hyperactivity. Moreover, the effect of pharmacologic treatment and the potential beneficial effect of renal denervation will be discussed.

Renal denervation as therapy for hypertension: potentials and unanswered questions

In 2005, cardiovascular diseases globally accounted for 30% of an estimated total of 58 million deaths. Hypertension is one of the major contributors to these events. Unfortunately, about two-thirds of all hypertensive patients do not reach treatment goals despite maximal drug treatment. Percutaneous catheter-based renal denervation as a therapy for uncontrolled hypertension is an intriguing idea, especially for patients with resistant hypertension. The first short-term results from a randomized trial are promising: 84% of the patients had a blood pressure (BP) reduction of ≥10 mmHg and 39% had a systolic BP of ≤140 mmHg 6 months after treatment. However, several questions remain unanswered. To gain more insight, initiatives should be started aiming at assessing safety of the treatment, sustainability of the BP-lowering effect, cost-effectiveness, and the effect on cardiovascular event rate. Many European centres have now started to perform renal denervation or are in the process of starting it up. Therefore, we call for an international collaboration effort to compose cohorts and conduct randomized trials to address the remaining issues at this point in time.

Optical coherence tomography findings in renal denervation

Percutaneous catheter-based renal denervation is an emerging technique to treat severe and ‘resistant’ arterial hypertension. We report the case of a 56-year-old woman who was considered as ‘resistant’ hypertensive despite being treated with four antihypertensive drugs (including one diuretic) and was referred for percutaneous catheter-based renal denervation to our institution. The procedure was performed in accordance with the manufacturer's …

Die renale Denervation als neue Behandlungsmöglichkeit der therapierefraktären arteriellen Hypertonie

Resistant hypertension is defined as blood pressure that remains above therapeutic goal despite the use of 3 antihypertensive drugs including a diuretic. After exclusion of secondary causes and medical in compliance, the estimated prevalence of resistant arterial hypertension ranges from 4% to 19% in hypertensive patients. Treatment requires a multimodal therapeutic approach. Hyperactivation of the sympathetic nervous system plays a key role in the genesis of hypertension. Targeting renal sympathetic nerves, percutaneous catheter-based renal denervation is a new therapeutic option for the treatment of resistant arterial hypertension in selected drug resistant patients.