Safety Of Renal Sympathetic Denervation Research Articles

The current state of renal sympathetic denervation in hypertension

This review provides an overview of the efficacy and safety of renal sympathetic denervation as a therapeutic approach for resistant hypertension. While the initial enthusiasm was sparked by the results of early clinical trials, it was dampened by the findings of the Symplicity HTN-3 study. However, recent advances in catheter technology and more refined patient selection criteria have yielded more promising results. Subsequent studies, such as SPYRAL HTN-OFF MED and RADIANCE II, demonstrated significant reductions in blood pressure, even in patients with mild to moderate hypertension. Despite the lack of robust data on major clinical outcomes, investigations into the time in therapeutic range for patients undergoing renal sympathetic denervation suggested potential cardiovascular benefits. Nevertheless, further research is needed to thoroughly understand the long-term impact, assess cost-effectiveness, and accurately identify which patient subgroups may derive the greatest benefits from this therapy.

Update on Renal Sympathetic Denervation for the Treatment of Hypertension.

Hypertension is a leading risk factor for all-cause mortality in adults; however, medication non-adherence and intolerance present an enormous treatment challenge. Given the critical role of renal sympathetic nerves in neurogenic control of blood pressure and pathophysiology of hypertension, renal sympathetic denervation (RDN) has been explored as a therapeutic strategy in hypertension treatment over the last 15years. In this review, we will discuss the role of renal sympathetic nerves in the pathophysiology of hypertension, provide an update on the available evidence regarding the short- and long-term safety and effectiveness of RDN in the treatment of hypertension, and consider its future perspectives. RDN is a percutaneous endovascular catheter-based neuromodulation approach that enables ablation of renal sympathetic nerve fibers within the adventitial layer of the renal arteries using radiofrequency (most extensively studied), ultrasound energy, or neurolytics (e.g., alcohol). In the last decade, advancements in procedural techniques and well-designed sham-controlled trials utilizing 24-h ambulatory blood pressure measurements have demonstrated that RDN has an excellent safety profile and results in a modest reduction of blood pressure, in a wide range of hypertensive phenotypes (mild to resistant), irrespective of antihypertensive drug use and this effect is sustained over a 3-year period. Superiority of a particular RDN modality has not been yet established. Despite strong evidence demonstrating efficacy and safety of RDN, current data does not support its use as a primary approach in the treatment of hypertension due to its modest treatment effect and concerns around long-term sustainability. Perhaps the best utility of RDN is in hypertensives intolerant to antihypertensive medications or as an adjunct to aldosterone antagonists in the management of resistant hypertension. Patient selection will be critical to demonstrate a meaningful benefit of RDN. Future well-designed studies are necessary to determine predictors and measures of response to RDN, long-term efficacy given question of renal nerve regeneration, comparison of available technologies, safety in patients with advanced kidney disease, and improvement in patient quality of life measures.

VIEWS AND PERSPECTIVES OF HYPERTENSION EXPERTS IN GREECE REGARDING THE EFFICACY AND SAFETY OR RENAL SYMPATHETIC DENERVATION

Objective: The role of renal sympathetic denervation (RSD) in the management of arterial hypertension remains controversial, given the initial enthusiasm by the first studies, the great disappointment by the first sham-controlled randomized study and the current promising finding in recent randomized trials. Therefore, an uncertainty exists about the beliefs of hypertension specialists regarding RSD. This analysis presents the opinions of hypertension experts in Greece regarding the efficacy and safety of RSD. Design and method: Chairpersons of ESH Hypertension Excellence Centers in Greece and their senior clinical research fellows, were invited to participate in a meeting aiming to discuss the current evidence on the clinical utility of RSD. Individual responses were recorded and qualitatively analyzed, in order to reach consensus about the safety and efficacy of RSD. Results: Twenty-five experts participated in the meeting (cardiologists 52%, internists 40%, nephrologists 8%). Participants agreed upon the favorable results of three recent clinical trials and supported the view that RSD is an effective method. 44% believe that further technological development of the denervation catheter is expected to improve the results of the technique. Importantly, 22% of the experts highlighted the additional benefits of the method in regressing target organ damage and in patients with increased activity of the sympathetic nervous system. However, 44% of the experts underlined the lack of reliable predictive markers for the efficacy of RSD, while 32% highlighted the lack of long-term efficacy studies. Experts universally agreed on the safety of the method. However, 64% stated that the duration of the RSD trials was short, and thus there is lack of data on the long-term safety of RDS. Of note, 76% considered the method as easy to perform and minimally invasive. Conclusions: The majority of the hypertension experts in Greece agree upon the efficacy of RSD and all had minimal concerns of the safety of method. More data are needed to reveal the degree of confidence among hypertension experts regarding the efficacy and the safety of the whole procedure and its specific aspects.

HYPERTENSIVE PATIENTS AS CANDIDATES FOR RENAL SYMPATHETIC DENERVATION: CONSENSUS OPINION OF HYPERTENSION EXPERTS IN GREECE

Objective: Several studies have evaluated the efficacy and safety of renal sympathetic denervation (RSD) in patients with hypertension and other conditions characterized by sympathetic overactivity. However, to date there is no consensus in the literature about which patients are the most appropriate candidates for RSD. This analysis presents the opinions of hypertension experts in Greece regarding potential candidates for RSD. Design and method: Chairpersons of ESH Hypertension Excellence Centers in Greece and their senior clinical research fellows, were invited to participate in a meeting aiming to discuss the current evidence on the clinical utility of RSD. Individual responses were recorded and qualitatively analyzed, in order to reach consensus about potential RSD candidates. Results: Twenty-five experts participated in the meeting (cardiologists 52%, internists 40%, nephrologists 8%). (i) 84% of the experts agreed that patients with resistant or uncontrolled hypertension are the most eligible candidates for RSD. (ii) Patients who are either non-adherent to treatment (72%) or discontinued antihypertensive drugs due to adverse events (64%) were suggested as potential candidates. (iii) Patients with severe left ventricular hypertrophy or other TOD were also proposed as potential candidates (24%). (iv) Individuals with diseases associated with sympathetic overactivity (72%), such as obstructive sleep-apnea syndrome, chronic kidney disease, heart failure, arrhythmias, and polycystic ovary syndrome. (v) Patients at the initial stages of hypertension (12%), women of child-bearing potential (4%), drug naïve patients (16%), and patients of young age without TOD were also considered (12%). (vi) Hypertensive patients with increased sympathetic activity, such as patients with excessive white-coat hypertension or sodium sensitivity, were also proposed as potential candidates (8%). (vii) Patients preferring RSD over life-long drug treatment might also be eligible (24%). Conclusions: Seven patient groups were identified as potential candidates for RSD. Experts agreed on the eligibility of patients with resistant hypertension, yet other groups of patients were also proposed. More data are needed to properly identify those patients who will benefit the most from RSD, aiming towards personalized therapy in this field.

Sham-Controlled Randomized Trials of Catheter-Based Renal Denervation in Patients With Hypertension

BackgroundThere are conflicting data regarding the relative effectiveness of renal sympathetic denervation (RSD) in patients with hypertension. ObjectivesThe purpose of this study was to evaluate the blood pressure (BP) response after RSD in sham-controlled randomized trials. MethodsDatabases were searched through June 30, 2018. Randomized trials (RCTs) with ≥50 patients comparing catheter-based RSD with a sham control were included. The authors calculated summary treatment estimates as weighted mean differences (WMD) with 95% confidence intervals (CIs) using random-effects meta-analysis. ResultsThe analysis included 977 patients from 6 trials. The reduction in 24-h ambulatory systolic blood pressure (ASBP) was significantly greater for patients treated with RSD than sham procedure (WMD −3.65 mm Hg, 95% CI: −5.33 to −1.98; p < 0.001). Compared with sham, RSD was also associated with a significant decrease in daytime ASBP (WMD −4.07 mm Hg, 95% CI: −6.46 to −1.68; p < 0.001), office systolic BP (WMD −5.53 mm Hg, 95% CI: −8.18 to −2.87; p < 0.001), 24-h ambulatory diastolic BP (WMD −1.71 mm Hg, 95% CI: −3.06 to −0.35; p = 0.01), daytime ambulatory diastolic BP (WMD −1.57 mm Hg, 95% CI: −2.73 to −0.42; p = 0.008), and office diastolic BP (WMD −3.37 mm Hg, 95% CI: −4.86 to −1.88; p < 0.001). Compared with first-generation trials, a significantly greater reduction in daytime ASBP was observed with RSD in second-generation trials (6.12 mm Hg vs. 2.14 mm Hg; p interaction = 0.04); however, this interaction was not significant for 24-h ASBP (4.85 mm Hg vs. 2.23 mm Hg; p interaction = 0.13). ConclusionsRSD significantly reduced blood pressure compared with sham control. Results of this meta-analysis should inform the design of larger, pivotal trials to evaluate the long-term efficacy and safety of RSD in patients with hypertension.

Magnetic resonance guided renal denervation using active tracking: first in vivo experience in Swine

Interventional cardiovascular magnetic resonance (iCMR) might evolve as a technique to improve procedural success rates in cardiovascular interventions by combining intraprocedural guidance and simultaneous lesion imaging. The objective of the present study was to prove feasibility and estimate safety of renal sympathetic denervation guided by real-time iCMR using active tracking. Six pigs were examined in a 1.5T MRI-System (Achieva, Philips Healthcare, Best, Netherlands) equipped with non-invasive hemodynamic control and in-room monitors displaying an interventional software platform [Interventional MRI Suite (iSuite), Philips Research, Hamburg, Germany]. MR-guided renal denervation was performed using a MR conditional non-irrigated ablation catheter with active tracking (Imricor, Burnsville, MN, USA). Real-time imaging for device guidance was performed with a TFE sequence, vessel patency was assessed with a 3D non-contrast angiography and velocity encoded imaging. Oedema of the renal artery was visualized by a high-resolution T2 SPIR sequence. Renal sympathetic denervation was feasible in all cases with survival of all animals. Non-contrast angiography displayed renal artery patency accompanied by equal flow conditions before and after the ablation in all cases as measured by velocity encoded imaging. Oedema imaging displayed a significant increase in relative signal intensity at renal artery ablations sites pre and post intervention (p < 0.05). The histologic examination revealed no signs of perforation or bleeding, while sufficient ablation lesions could be depicted. MR-guided renal sympathetic denervation using active tracking is feasible and the initial data suggest safety of this procedure. MR-guided renal sympathetic denervation offers the inherent strength of high soft tissue contrast thereby providing target information without the use of iodinated contrast agents or radiation.

Pulmonary vein isolation alone and combined with renal sympathetic denervation in chronic kidney disease patients with refractory atrial fibrillation

BackgroundAtrial fibrillation (AF) commonly occurs in association with chronic kidney disease (CKD), resulting in adverse outcomes. Combining pulmonary vein isolation (PVI) and renal sympathetic denervation (RSD) may reduce the recurrence of AF in patients with CKD and hypertension. We considered that RSD could reduce the recurrence of AF in patients with CKD by modulating sympathetic hyperactivity. Our goal was to compare the impact of PVI + RSD with that of PVI alone in patients with concurrent AF and CKD. MethodsThis was a single-center, prospective, longitudinal, randomized, double-blind study. Forty-five patients with controlled hypertension, symptomatic paroxysmal AF and/or persistent AF, stage 2 or 3 CKD, and a dual-chamber pacemaker were enrolled from January 2014 to January 2015. We assessed the 30-second recurrence of AF recorded by the pacemaker, 24-hour ambulatory blood pressure measurements, estimated glomerular filtration rate, albuminuria, echocardiographic parameters, and safety of RSD. ResultsNo patient developed procedural or other complications. The ambulatory blood pressure measurements did not differ within the PVI + RSD group or between the PVI + RSD and PVI groups throughout the study. Significantly more patients in the PVI + RSD group than in the PVI group were free of AF at the 12-month follow-up evaluation. The PVI group had an unacceptable response to ablation with respect to changes in echocardiographic parameters, whereas these parameters improved in the PVI + RSD group. ConclusionPVI + RSD were associated with a lower AF recurrence rate than PVI alone; it also improved renal function and some echocardiographic parameters. These encouraging data will serve as baseline information for further long-term studies on larger patient populations.

Efficacy and Safety of Renal Sympathetic Denervation on Dogs with Pressure Overload-Induced Heart Failure.

In dogs with heart failure (HF) induced by overload pressure, the role of renal sympathetic denervation (RSD) on heart failure and in the renal artery is unclear. Therefore, we investigated the efficacy and safety of RSD in dogs with pressure overload-induced heart failure. Twenty mongrel dogs were divided into a sham-operated group, an HF group and an HF + RSD group. In the sham-operated group, the abdominal aorta was located but was not constricted, in the HF group, the abdominal aorta was constricted without RSD, and the HF+RSD group underwent RSD with constriction of the abdominal aorta after 10 weeks. Blood sampling assays, echocardiography, intravascular ultrasound (IVUS) measurement and histopathological examination were performed. Renal sympathetic denervation caused a significant reduction in the levels of noradrenaline (166.62±6.84 vs. 183.48±13.66 pg/ml, P<0.05), plasma renin activity (1.93±0.12 vs. 2.10±0.13 ng/mlh, P<0.05) and B-type natriuretic peptide (71.14±3.86 vs. 83.15±5.73 pg/ml, P<0.05) at eight weeks after RSD in the HF+RSD group. Compared with the HF group at eight weeks, the left ventricular internal dimension at end-diastole and end-systole were lower and the left ventricular ejection fraction was higher (all P<0.05) at eight weeks after RSD in the HF+RSD group. Intravenous ultrasound images showed no changes in the renal artery lumen, and intimal hyperplasia and vascular lumen stenosis were not observed after RSD. Renal sympathetic denervation could improve cardiac function in dogs with HF induced by pressure overload; RSD had no adverse influence on the renal artery.

Safety and feasibility of transcatheter renal sympathetic denervation using different types of catheter and various radiofrequency settings

BackgroundTo evaluate in vivo the feasibility and safety of renal sympathetic denervation (RSD) with different catheters and various radiofrequency protocols. Methods and resultsTwenty-two pigs were included. First 2 pigs were enrolled in a feasibility protocol using one catheter and power from 5W to 20W. The next 10 pigs underwent RSD with three different catheters and four different RF-power settings of 5W, 8W, 10W and 12W in one minute per lesion (Protocol 1). The following 10 (Pigs 13 to 22) underwent RSD with five types of catheters (including the Symplicity® catheter), powers of 8W and 10W and two minutes RF-application (Protocol 2). Angiographic data were obtained at baseline, during and after RSD. At last, renal arteries were excised and analyzed macroscopically. The first pig developed severe renal stenoses with lesions of 15 to 20W correlated with macroscopic alterations. The second feasibility pig did not develop renal stenosis with 5 and 8W. In Protocol 1 from 60 RF-lesions, we observed 7 stenoses (≥30%). Three were severe (one of 80% with 10W and two of 80% with 12W). In Protocol 2 from 57 lesions we observed only 1 stenosis of 50% with 8W with Symplicity® catheter. Severe stenosis was not observed. ConclusionIn this study, renal sympathetic denervation showed safety using five types of catheters when applying RF-energy less than 10W, within main stems of arteries larger than 3.0mm diameter and a distance between lesions of at least 1 time catheter tip length.

Efficacy and safety of renal denervation in elderly patients with resistant hypertension

Catheter-based renal sympathetic denervation (RD) causes significant blood pressure (BP) reductions in patients with resistant hypertension (rHTN). However, hypertensive elderly patients reportedly have a lower sympathetic tone than younger patients and a BP lowering effect of RD in this population has not yet been demonstrated. The purpose of this study was to assess the efficacy and safety of RD in elderly patients. We reviewed all consecutive patients aged ≥ 75 years (mean: 78 years) with rHTN treated with RD. Twenty-four patients were included in this prospective study. Office and ambulatory BPs were assessed at baseline and 6-months follow-up. Primary endpoint was the change in office systolic BP at 6 months. Baseline mean office BP was 173/86 ± 21/13 mm Hg. Baseline 24-hr mean ambulatory BP, available in 22 patients, was 158/80 ± 20/13 mm Hg. Baseline creatinine was 1.0 ± 0.18 mg/dl and mean number of antihypertensive agents at baseline 4.3 ± 1.4. No device- or procedure-related adverse events occurred. At 6-months follow-up, the mean office BP decreased by 19/11 ± 29/16 mm Hg (P < 0.01 compared to baseline). Mean systolic 24 hr ambulatory BP, available in 17 patients, decreased by 9/5 ± 13/13 mm Hg. Antihypertensive medications could be reduced in nine patients. Furthermore, renal function was not impaired. According to our findings, a similar magnitude of BP reduction as reported in previous trials can be expected in elderly patients. Elderly patients with rHTN should not be excluded from renal denervation.

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Objective: To systematically evaluate the efficiency and safety of renal sympathetic denervation for resistant hypertension. Design and method: Such databases as The Cochrane Library, PubMed, EMbase, CBM and CNKI were electronically searched for relevant studies from inception to July 2014. Two reviewers independently screened literature according to the inclusion and exclusion criteria as well as the methods recommended by the Cochrane Collaboration, extracted data, and assessed the methodological quality of the included studies. Then, meta analysis was performed using RevMan 5.2 software. Results: Four randomized controlled trialsand totally 1649 patients. The results of meta-analysis suggested that there was a reduction in mean systolic and diastolic blood pressure at 3 months of - 22.39 mmHg and - 6.75 mmHg. And a reduction in mean systolic and diastolic blood pressure at 6 months of – 17.93 mmHg and – 9.33 mmHg (902 patients). The results showed RSD was superior to the medical therapy in reducing mean systolic blood pressure and mean diastolic blood pressure. In observation studies, there was a reduction in mean systolic and diastolic BP at 3 months of – 24.35 mm Hg and – 9.45mmHg (–12.33 to –6.58 mmHg), and there was a reduction in mean systolic and diastolic BP at 6 months of–27.25mmHg (– 33.1 to – 21.39mmHg) and –10.25 mmHg (–12.59 to –7.92 mmHg), The results showed great reduction of mean systolic blood pressure, diastolic blood pressure after RSD (p < 0.01). There was no significant difference in the effect of RSD with 6 kinds of catheters. No obvious damages were discovered after RSD besides 4 femoral pseudoaneurysms. Conclusions: Based on current evidence, RSD performed better than medical therapy in the treatment of resistant hypertension patients, and performed more security. However, due to the quality of the included studies, the clinical effects of RSD on RH patients need to be confirmed by large-scale and multicenter randomized controlled trials in the future.

Renal sympathetic denervation for treatment of resistant hypertension: a meta-analysis

Objective To systematically evaluate the effectiveness and safety of renal sympathetic denervation (RSD) for treatment of patients with resistant hypertension. Methods English and Chinese literatures of controlled clinical trials on RSD in treatment of resistant hypertension were searched from the Cochrane Library, PubMed, Web of Science, Wanfang Database and CNKI up to February 2013.Meta-analysis was performed with the selected studies by using software Rev.Man 5.0. Results Seven studies involving 354 cases with RSD and 146 controls were included for analysis.Compared with control group, RSD significantly lower both systolic and diastolic blood pressure in patients with resistant hypertension (systolic, 1 month: MD=-18.04, 95%CI: -19.94--16.14, P<0.01; 3 months: MD=0.01, 95%CI: -28.10--17.98, P<0.01; 6 months: MD=-25.59, 95%CI: -34.08--17.11, P<0.01; diastolic, 1 month: MD=-7.53, 95%CI: -8.60--6.45, P<0.01; 3 months: MD=0.01, 95%CI: -12.5--4.47, P<0.01; 6 months: MD=-10.54, 95%CI: -16.44--4.63, P=0.000 5). In addition, there was no significant difference in adverse reactions between RSD treatment group and control group (OR=1.13, 95%CI: 0.34-3.76, P=0.84). Conclusions Renal sympathetic denervation can effectively reduce blood pressure in patients with resistant hypertension 1-6 months postoperatively, without increase of adverse reactions.The long-term efficacy and safety need to be further observed. Key words: Sympathectomy; Hhypertension; Meta-analysis

CONGRESS COVERAGE: Renal Sympathetic Denervation for Resistant Hypertension: Symplicity HTN-3 and the Power of Placebo

CONGRESS COVERAGE: Renal Sympathetic Denervation for Resistant Hypertension: Symplicity HTN-3 and the Power of Placebo

Results of the ALSTER BP real-world registry on renal denervation employing the Symplicity system

To prove the efficacy and safety of renal sympathetic denervation as a new treatment option for patients suffering from resistant hypertension in a real-world setting. This single-centre real-world registry included 93 patients who underwent renal denervation employing the Symplicity system. Patients were followed for six months. The patient cohort was divided into early responders with a reduction of office systolic blood pressure >10 mmHg three months after the procedure (n=53, 57%), late responders (six months after the procedure, n=16, 17%) and non-responders (n=24, 26%). After six months, systolic blood pressure was lowered by 46±2.9 mmHg (mean±SEM, p<0.001), 31±3.4 mmHg (p<0.001) and 7.1±3.3 mmHg (p=0.79, ns), respectively. Ambulatory blood pressure monitoring also showed a significant reduction in the early responder group (20±5.7 mmHg, p=0.002). We subjected eight patients to a re-do procedure which led to a significant reduction of blood pressure in another five patients after six months (63%). One patient in this cohort developed a one-sided renal artery stenosis associated with an increase in blood pressure. This real-world analysis of renal sympathetic denervation confirms the procedure to be safe and efficient in the majority of patients. Non-responders may profit from a second ablation, arguing in favour of the hypothesis that the procedure did not destroy sufficient amounts of sympathetic innervation in these patients. However, repeated denervations may also increase side effects.

Renal sympathetic denervation using an open-irrigated catheter in 10 patients with confirmed resistant hypertension

Purpose: Catheter-based renal sympathetic denervation (RSD) has emerged as an alternative strategy for blood pressure (BP) control in patients with resistant hypertension. Recently an irrigated catheter was evaluated in a proof-of-principle study, but none of the previous studies have confirmed patient resistance with hospitalization. The aim of this study was to assess the efficacy and safety of RSD using an irrigated catheter in patients with drug-resistant hypertension confirmed by pervious hospitalization. Methods: Patients that kept the resistance criteria defined by the 7th Joint after a hospitalization period were referred to RSD. The procedure was carried out in a helicoidally manner using an open-irrigated catheter with a power of 15W, aiming to achieve a 10% impedance drop at each location. Four to 6 lesions (60sec each) were placed in each artery. Patients were followed-up (FU) at 1, 3, and 6 months. Renal artery angiography will be done at 6-months FU. Results: Ten patients (mean age 47.3 yo, 90% female) underwent RSD. The mean hospitalization period was 7 days and the mean number of anti-hypertensive drugs prior to the procedure was 7 (ranging from 4 to 9 drugs). In the mean FU of 3 months, the mean reduction of systolic and diastolic BP were12.5 and 6.2 mmHg, respectively; and the number of drugs required for BP control dropped to a mean of 4.3. Renal artery dissection (caused by the long sheath) occurred in the first case, and it was successfully treated with stent implantation. No subsequent adverse events occurred, suggesting the effects of the learning curve. No complications such as renal artery damage, renal infarction, acute renal failure, thrombus at the electrode tip or pulmonary edema were reported. Six months angiography and BP results are pending. Conclusions: In a mean FU of 3 months, RSD using a open irrigated catheter was safe and feasible in treating confirmed resistant hypertension. Randomized studies are needed to support our results.

Renal Denervation in the Treatment of Hypertension

Despite advances in nonpharmacologic and pharmacologic therapy, blood pressure control rates in hypertension are low. About 10% of patients with hypertension fulfill the criteria of therapy resistance, which is defined as noncontrolled blood pressure despite treatment with ≥3 antihypertensive drugs of different classes, including a diuretic, at optimal or maximal tolerated doses. Although the pathogenesis of resistant hypertension is multifactorial, an interaction between renal afferent and efferent sympathetic nerves and the central nervous system plays a key role, leading to increased renal and central sympathetic activity. Catheter-based renal sympathetic denervation (RDN) is a novel therapeutic technique for the treatment of resistant hypertension. Clinical trials of RDN have shown a significant and sustained reduction of blood pressure as well as renal and central sympathetic activity. In clinical practice, appropriate patient selection is crucial to ensure successful and safe treatment. Beyond hypertension, RDN was associated with reduction of heart rate, regression of left ventricular mass, and improvements in glucose metabolism and severity of sleep apnea. Further studies addressing open questions in the treatment of resistant hypertension and evaluating potential new indications such as metabolic syndrome or heart failure (RE-ADAPT-HF) are necessary to prove effectiveness and safety of RDN in these patients. By modulating sympathetic activity, RDN has the potential to provide benefit in a variety of diseases, but these concepts have to be evaluated in well-designed prospective controlled clinical trials.

Efficacy of renal denervation with a standard EP catheter in the 24-h ambulatory blood pressure monitoring—long-term follow-up

Resistant hypertension (HTN), defined as ambulatory blood pressure (BP) above 140/90 mmHg in spite of the concurrent use of three or more antihypertensive drugs, is a serious global health issue. It has been estimated that it may affect 20% to 30% of the HTN population [1]. Only about 30% of these patients are actually adequately controlled according to the target BP. A critical factor in resistant HTN is the hyperactivity of the sympathetic nervous system, which increases progressively and in parallel with HTN stages, indicating that more advanced stages of HTN have a greater adrenergic activity [2]. Recent research could show that catheter-based renal sympathetic denervation is effective in BP lowering in patients with resistant hypertension [3–7]. Usually, a special ablation catheter (Symplicity®, Flex-Catheter, Medtronic/Ardian Inc. USA) is used for this purpose. We could recently show that sympathetic denervation with a standard electrophysiology (EP) catheter is also effective in reduction of blood pressure during 3month follow-up (FU) [7]. The aim of this study was to evaluate the efficacy (measured in the 24-h ambulatory BPmonitoring) and safety of renal sympathetic denervation by using a standard EP catheter during long-term FU (12 months) with a larger group of patients. Therefore, 30 patients with drug-resistant hypertension despite treatment with at least four antihypertensive drugs (mean 6) were treated with RF ablation of the renal artery for sympathetic denervation. Baseline evaluation of patients included physical examination, review of medications, basic blood chemistries (including serum creatinine and proteinuria), and 24-h ambulatory BP measurement. All patients have had secondary forms of hypertension excluded. Baseline parameters and comorbidity of patients are shown in Table 1. The method of the ablation procedure with a standard EP catheter has been previously described indetail [7]. In brief, renal artery stenosiswas excludedby renal angiogram via femoral access. After this, a standard steerable radiofrequency (RF) ablation catheter with a 7-French diameter (Marinr®; Medtronic Inc., Minneapolis, MN, USA) was introduced into both renal arteries, consecutively. We applied six low-power RF applications along the length of each renal artery to create lesions (up to 1 min each). Energy delivery was titrated up to a maximum of 8–13 watts under continuously monitoring of impedance and temperature. During RF ablation, we administered intravenous unfractionated heparin with an activated clotting time target range between 250 and 300 s. Aspirin (100 mg per day) was given at least for 3 months following the procedure. Since RF ablation was accompanied by diffuse visceral abdominal pain, patients received intravenous analgesia (fentanyl at doses up to 0.15 mg and midazolam at doses up to 4 mg). The final renal angiogram at procedure termination showed only renal artery irregularities which were not flow limiting. The median fluoroscopy time in our study was 7.5±3.4 min. We did not observe any complications or side effects during FU. The mean reduction of 24-h ambulatory BP was −15.5 mmHg in systolic BP (p=0.01) and −3.4 mmHg in diastolic BP (p=0.03) at 1 month (n=30), −25.5 mmHg in systolic BP (p=0.0001) and −10.9 mmHg in diastolic BP (p=0.01) at 3 months (n=30), −24.1 mmHg in systolic BP (p=0.0003) and −10.6 mmHg in diastolic BP (p=0.002) at 6 months (n=20), and −15 mmHg in systolic BP (p=0.04) and −4.3 mmHg in diastolic BP (not significant) at 12 months (n=10). The results are shown in Fig. 1. In six patients the number of different drugs could be reduced (−1 in five patients, −2 in one patient) and in one patient the medication increased from 5 to 6 different drugs at 6-month FU. All other patients received unchanged doses of antihypertensive drugs. Serum creatinine and proteinuria as markers of renal function remained stable in the FUperiod. Renal duplex sonography performed at 3 and at 12 months revealed no renal artery stenosis or other abnormalities in all patients. The blood-pressure-lowering in our study was a little less than described in the Symplicity HTN trials that found a reduction in officebased BP of −32/−12 mmHg after 6 months [8] and −27/−17 mmHg after 12 months [3]. However, these differences might be due to methodical aspects. In contrast to the measurement of office-based BP by the Symplicity HTN-1 and HTN-2 investigators, we used 24-h ambulatory BP measurements for our analysis, possibly depicting more real life proportions of blood-pressure-lowering. In fact, the 24-h BP monitoring, which was available in 20 patients of the Symplicity HTN-2 trial at 6 months, showed only a decrease of −11/−7 mmHg from baseline to 6 months follow-up [8], underscoring the efficacy of our approach. Furthermore, after 6 months, 80% of our patients were responders to our treatment, defined by a reduction in BP of 10 mm Hg ormore, which is comparable with the response rate of 84% in the HTN-2 trial. However, we recognize that the small number of patients, especially

Radiofrequency ablation for resistant hypertension: a report of three cases

ObjectiveTo evaluate the efficacy and safety of renal sympathetic denervation by radiofrequency ablation for patients with resistant hypertension and discuss the experience in the operation.MethodsThree patients with resistant hypertension received...