Renal denervation in the management of hypertension.

Arterial hypertension is a global leading cause of cardiovascular, cerebrovascular, and renal disease, as well as mortality. Although pharmacotherapy is safe and effective in lowering blood pressure (BP) and cardiovascular disease risk, BP control remains poor, and the mortality rates associated with high BP have been steadily increasing. Device-based therapies have been investigated to overcome barriers to pharmacotherapy, including non-adherence and low rates of persistence to daily medications. Among these device-based therapies, catheter-based renal denervation (RDN) has been most extensively examined over the past 15 years. In this state-of-the-art article, we summarise the rationale for RDN, review the available evidence, provide recommendations for a safe procedure, and discuss the role of RDN in current guidelines and clinical practice.

Impact of renal denervation on patients with coronary microvascular dysfunction: study rationale and design.

AIMS: Long-standing hypertension may cause an impairment in microvascular coronary circulation, which is involved in many different cardiac conditions. Renal sympathetic denervation (RDN) has been successfully proven as a valuable therapeutic choice for patients with resistant hypertension; moreover, the procedure looks promising in other settings, such as heart failure and atrial fibrillation, given its ability to downregulate the sympathetic nervous system, which is a recognized driver in these conditions as well as in microvascular dysfunction progression. The aim of this study is to explore the effect of RDN on coronary physiology in patients with ascertained coronary microvascular dysfunction and resistant hypertension. METHODS: This is a multicenter, prospective, nonrandomized, open-label, interventional study. Consecutive patients with resistant hypertension, nonobstructive coronary artery disease (NOCAD) and documented microvascular dysfunction will be enrolled. Patients will undergo RDN by Spyral Symplicity 3 (Medtronic Inc, Minneapolis, Minnesota, USA) and reassessment of coronary microvascular function 6 months after the procedure. Primary endpoint will be the difference in the index of microcirculatory resistance. CONCLUSION: The IMPRESSION study seeks to evaluate if there is any pleiotropic effect of the RDN procedure that results in modulation of microvascular function; if observed, this would be the first evidence showing RDN as a valuable therapy to revert hypertension-related microvascular dysfunction.

Efficacy and safety of 3D reconstruction and basket multi-electrode renal denervation (RDN) for refractory hypertensive patients with chronic kidney disease.

Renal Artery Sympathetic Denervation (RDN) can lower blood pressure. Different ablation catheters (single electrode, multi-electrode) have different scopes of ablation (renal artery main stem and branches). Few studies have compared the advantages and disadvantages of different ablation catheters and different procedures in terms of antihypertensive efficacy. To compare the efficacy and safety of 3D reconstruction radiofrequency ablation (3DRA) and basket multi-electrode radiofrequency ablation (BMRA) in Renal Artery Sympathetic Denervation. Fifty-three patients with Refractory hypertension (RHT) were divided into BMRA, (n = 28) and 3DRA(n = 25). BMRA group used a stereobasket multi-electrode ablation catheter with a controlled ablation temperature of 60°C and an ablation time of 120 s per site. 3DRA group used a NavStar pressure-monitored perfusion monopolar ablation catheter with a controlled ablation temperature of 40°C, an ablation time of 40 s per site, and an ablation energy of 12 W. Baseline and RDN parameters and complications were compared in both groups. Home and 24 h ambulatory blood pressure, type of anti-hypertensive medication taken, and serum creatinine were followed up at 1, 3, 6, 12, and 24 months after the RDN. There were no differences in baseline characteristics between the two groups. (23.14 ± 2.00)months of follow-up in the BMRA group resulted in a total of (25.86 ± 8.61) loci ablation. (19.28 ± 7.40)months of follow-up in the 3DRA group resulted in a total of (21.04 ± 6.47)loci ablation. Home SBP was significantly lower in both groups at 1 month after RDN treatment compared to baseline(H-SBP/mmHg: BMRA 149.9 ± 10.59 vs. baseline 168.36 ± 12.76; 3DRA 152.6 ± 14.91 vs. 164.89 ± 12.96, both p < .05). The proportion of people with 24 h ambulatory SBP attainment was significantly higher in both groups and was maintained for 24 months. At each follow-up time point, there were no differences in home and 24-h flow SBP, DBP, or Scr between the two groups. There were two cases of severe renal artery complications from implanted vascular stents and one case of femoral artery pseudoaneurysm in the 3DRA group. At follow-up, 1 (1.9%) patient in the 3DRA group died of unexplained death and 1 (1.9%) patient developed heart failure, and 1 (1.9%) patient in the BMRA group died of unexplained death. Basket multi-electrode radiofrequency ablation and 3D reconstruction radiofrequency ablation of the renal artery applied to RDN have comparable efficacy in reducing systolic blood pressure.

Echocardiographic findings following renal sympathetic denervation for treatment resistant hypertension, the ReShape CV-risk study.

OBJECTIVE: The aim of this study was to describe and compare echocardiographic findings before renal sympathetic denervation (RDN) and 6 and 24 months after the procedure. MATERIALS AND METHODS: Patients with treatment resistant hypertension (TRH) were included in this non-randomised intervention study. RDN was performed by a single experienced operator using the Symplicity Catheter System. Echocardiographic measurements were performed at baseline, and after 6 and 24 months. RESULTS: The cohort consisted of 21 patients with TRH, with a mean systolic office blood pressure (BP) of 163 mmHg and mean diastolic BP 109 mmHg. Mixed model analysis showed no significant change in left ventricular (LV) mass index (LVMI) or left atrium volume index (LAVI) after the RDN procedure. Higher LVMI at baseline was significantly associated with greater reduction in LVMI (p < 0.001). Relative wall thickness (RWT) increased over time (0.48 mm after two years) regardless of change in BP. There was a small but significant reduction in LV end-diastolic (LVIDd) and end-systolic (LVIDs) diameters after RDN, with a mean reduction of 2.6 and 2.4 mm, respectively, after two years. Progression to concentric hypertrophy was observed only in in patients who did not achieve normal BP values, despite BP reduction after RDN. CONCLUSION: There was no reduction of LV mass after RDN. We found a small statistically significant reduction in LVIDd and LVIDs, which together with increase in RWT can indicate progression towards concentric hypertrophy. BP reduction after RDN on its own does not reverse concentric remodelling if target BP is not achieved.

Early Renal Denervation Attenuates Cardiac Dysfunction in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: The renal sympathetic nervous system modulates systemic blood pressure, cardiac performance, and renal function. Pathological increases in renal sympathetic nerve activity contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). We investigated the effects of renal sympathetic denervation performed at early or late stages of HFpEF progression. METHODS AND RESULTS: Male ZSF1 obese rats were subjected to radiofrequency renal denervation (RF-RDN) or sham procedure at either 8 weeks or 20 weeks of age and assessed for cardiovascular function, exercise capacity, and cardiorenal fibrosis. Renal norepinephrine and renal nerve tyrosine hydroxylase staining were performed to quantify denervation following RF-RDN. In addition, renal injury, oxidative stress, inflammation, and profibrotic biomarkers were evaluated to determine pathways associated with RDN. RF-RDN significantly reduced renal norepinephrine and tyrosine hydroxylase content in both study cohorts. RF-RDN therapy performed at 8 weeks of age attenuated cardiac dysfunction, reduced cardiorenal fibrosis, and improved endothelial-dependent vascular reactivity. These improvements were associated with reductions in renal injury markers, expression of renal NLR family pyrin domain containing 3/interleukin 1ß, and expression of profibrotic mediators. RF-RDN failed to exert beneficial effects when administered in the 20-week-old HFpEF cohort. CONCLUSIONS: Our data demonstrate that early RF-RDN therapy protects against HFpEF disease progression in part due to the attenuation of renal fibrosis and inflammation. In contrast, the renoprotective and left ventricular functional improvements were lost when RF-RDN was performed in later HFpEF progression. These results suggest that RDN may be a viable treatment option for HFpEF during the early stages of this systemic inflammatory disease.

Impact of Antihypertensive Medication Changes After Renal Denervation Among Different Patient Groups: SPYRAL HTN-ON MED.

BACKGROUND: The SPYRAL HTN-ON MED (Global Clinical Study of Renal Denervation With the Symplicity Spyral Multi-electrode Renal Denervation System in Patients With Uncontrolled Hypertension in the Absence of Antihypertensive Medications)trial showed significant office and nighttime systolic blood pressure (BP) reductions in patients with hypertension following renal denervation (RDN) compared with sham-control patients, despite similar 24-hour BP reductions. We compared antihypertensive medication and BP changes among prespecified subpopulations. METHODS: The multicenter, randomized, sham-controlled, blinded SPYRAL HTN-ON MED trial (n=337) evaluated BP changes after RDN compared with a sham procedure in patients with hypertension prescribed 1 to 3 antihypertensive drugs. Most patients (n=187; 54%) were enrolled outside the United States, while 156 (46%) US patients were enrolled, including 60 (18%) Black Americans. RESULTS: Changes in detected antihypertensive drugs were similar between RDN and sham group patients in the outside US cohort, while drug increases were significantly more common in the US sham group compared with the RDN group. Patients from outside the United States showed significant reductions in office and 24-hour mean systolic BP at 6 months compared with the sham group, whereas BP changes were similar between RDN and sham in the US cohort. Within the US patient cohort, Black Americans in the sham control group had significant increases in medication burden from baseline through 6 months (P=0.003) but not in the RDN group (P=0.44). CONCLUSIONS: Patients enrolled outside the United States had minimal antihypertensive medication changes between treatment groups and had significant office and 24-hour BP reductions compared with the sham group. Increased antihypertensive drug burden in the US sham cohort, especially among Black Americans, may have diluted the treatment effect in the combined trial population. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02439775.

Salt sensitivity risk derived from nocturnal dipping and 24-h heart rate predicts long-term blood pressure reduction following renal denervation.

BACKGROUND: Renal denervation (RDN) has been consistently shown in recent sham-controlled clinical trials to reduce blood pressure (BP). Salt sensitivity is a critical factor in hypertension pathogenesis, but cumbersome to assess by gold-standard methodology. Twenty-four-hour average heart rate (HR) and mean arterial pressure (MAP) dipping, taken by ambulatory blood pressure monitoring (ABPM), stratifies patients into high, moderate, and low salt sensitivity index (SSI) risk categories. OBJECTIVES: We aimed to assess whether ABPM-derived SSI risk could predict the systolic blood pressure reduction at long-term follow-up in a real-world RDN patient cohort. METHODS: Sixty participants had repeat ABPM as part of a renal denervation long-term follow-up. Average time since RDN was 8.9 ±â€Š1.2 years. Based on baseline ABPM, participants were stratified into low (HR < 70 bpm and MAP dipping > 10%), moderate (HR ≥70 bpm or MAP dipping ≤ 10%), and high (HR ≥ 70 bpm and MAP dipping ≤ 10%) SSI risk groups, respectively. RESULTS: One-way ANOVA indicated a significant treatment effect ( P  = 0.03) between low ( n  = 15), moderate ( n  = 35), and high ( n  = 10) SSI risk with systolic BP reduction of 9.6 ±â€Š3.7 mmHg, 8.4 ±â€Š3.5 mmHg, and 28.2 ±â€Š9.6 mmHg, respectively. Baseline BP was not significantly different between SSI Risk groups ( P  = 0.18). High SSI risk independently correlated with systolic BP reduction ( P  = 0.02). CONCLUSIONS: Our investigation indicates that SSI risk may be a simple and accessible measure for predicting the BP response to RDN. However, the influence of pharmacological therapy on these participants is an important extraneous variable requiring testing in prospective or drug naive RDN cohorts.

Ten-year follow-up of very-high risk hypertensive patients undergoing renal sympathetic denervation.

OBJECTIVES: Renal denervation (RDN) has been proven to be effective in lowering blood pressure (BP) in patients, but previous studies have had short follow-ups and have not examined the effects of RDN on major cardiovascular outcomes. This study aimed to demonstrate the effectiveness and safety of RDN in the long-term treatment of hypertension and to determine if it has an effect on cardiovascular outcomes. METHODS: All patients with resistant hypertension who underwent RDN between 2011 and 2015 at Tianjin First Central Hospital were included in the study. Patients were followed up at 1,5 and 10 years and the longest follow-up was 12 years. Data were collected on office BP, home BP, ambulatory BP monitoring (ABPM), renal function, antihypertensive drug regimen, major adverse events (including acute myocardial infarction, stroke, cardiovascular death and all cause death) and safety events. RESULTS: A total of 60 participants with mean age 50.37 ±â€Š15.19 years (43.33% female individuals) completed long-term follow-up investigations with a mean of 10.02 ±â€Š1.72 years post-RDN. Baseline office SBP and DBP were 179.08 ±â€Š22.05 and 101.17 ±â€Š16.57 mmHg under a mean number of 4.22 ±â€Š1.09 defined daily doses (DDD), with a reduction of -35.93/-14.76 mmHg as compared with baseline estimates ( P  < 0.0001). Compared with baseline, ambulatory SBP and DBP after 10-years follow-up were reduced by 14.31 ±â€Š10.18 ( P  < 0.001) and 9 ±â€Š4.35 ( P  < 0.001) mmHg, respectively. In comparison to baseline, participants were taking fewer antihypertensive medications ( P  < 0.001), and their mean heart rate had decreased ( P  < 0.001). Changes in renal function, as assessed by estimated glomerular filtration rate (eGFR) and creatinine, were within the expected rate of age-related decline. No major adverse events related to the RDN procedure were observed in long-term consequences. All-cause mortality and cardiovascular mortality rates were 10 and 8.34%, respectively, for the 10-year period. CONCLUSION: The BP-lowering effect of RDN was safely sustained for at least 10 years post-procedure. More importantly, to the best of my knowledge, this is the first study to explore cardiovascular and all-cause mortality at 10 years after RDN.

Renal denervation restores biomechanics of carotid arteries in a rat model of hypertension.

The prevalence of hypertension increases with aging and is associated with increased arterial stiffness. Resistant hypertension is presented when drug treatments fail to regulate a sustained increased blood pressure. Given that the mechanisms between the sympathetic nervous system and the kidney play an important role in blood regulation, renal denervation (RDN) has emerged as a therapeutic potential in resistant hypertension. In this study, we investigated the effects of RDN on the biomechanical response and microstructure of elastic arteries. Common carotid arteries (CCA) excised from 3-month, 8-month, and 8-month denervated rats were subjected to biaxial extension-inflation test. Our results showed that hypertension developed in the 8-month-old rats. The sustained elevated blood pressure resulted in arterial remodeling which was manifested as a significant stress increase in both axial and circumferential directions after 8 months. RDN had a favorable impact on CCAs with a restoration of stresses in values similar to control arteries at 3 months. After biomechanical testing, arteries were imaged under a multi-photon microscope to identify microstructural changes in extracellular matrix (ECM). Quantification of multi-photon images showed no significant alterations of the main ECM components, elastic and collagen fibers, indicating that arteries remained intact after RDN. Regardless of the experimental group, our microstructural analysis of the multi-photon images revealed that reorientation of the collagen fibers might be the main microstructural mechanism taking place during pressurization with their straightening happening during axial stretching.

Renal Denervation in End-Stage Renal Disease: Current Evidence and Perspectives.

In patients with end-stage renal disease (ESRD) undergoing haemodialysis, hypertension is of common detection and frequently inadequately controlled. Multiple pathophysiological mechanisms are involved in the development and progression of the ESRD-related high blood pressure state, which has been implicated in the increased cardiovascular risk reported in this hypertensive clinical phenotype. Renal sympathetic efferent and afferent nerves play a relevant role in the development and progression of elevated blood pressure values in patients with ESRD, often leading to resistant hypertension. Catheter-based bilateral renal nerves ablation has been shown to exert blood pressure lowering effects in resistant hypertensive patients with normal kidney function. Promising data on the procedure in ESRD patients with resistant hypertension have been reported in small scale pilot studies. Denervation of the native non-functioning kidney's neural excitatory influences on central sympathetic drive could reduce the elevated cardiovascular morbidity and mortality seen in ESRD patients. The present review article will focus on the promising results obtained with renal denervation in patients with ESRD, its mechanisms of action and future perspectives in these high risk patients.

The feasibility, efficacy, and safety of RDN procedure using CO2 angiography through radial artery in severe chronic kidney disease patients.

The recent evidence regarding the effectiveness of renal denervation (RDN) in blood pressure control is becoming increasingly substantial. However, many studies have excluded populations with severely impaired kidney function, even though these individuals have a higher prevalence of hypertension compared to the general population, and controlling their blood pressure is more challenging. The effectiveness and safety of RDN in patients with severe chronic kidney disease (CKD) lack strong evidence support. Concerns about worsening kidney function still exist, particularly in patients with CKD stage 5. We conducted an observational study involving 10 patients who were using at least 3 different antihypertensive medications and had an estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2 but had not undergone dialysis. For these patients, we performed RDN via the radial artery approach, with the assistance of carbon dioxide (CO2) angiography. Utilizing this approach, the systolic 24-hour ambulatory blood pressure monitoring did not exhibit a significant decrease at 3 months; however, a significant reduction was observed at 6 months after RDN. We also minimized contrast agent usage, observed no kidney function decline 3 months post-RDN, and experienced no vascular-related complications. Using the radial artery approach and CO2 angiography assistance for RDN may be an effective and safe blood pressure control method for patients with severe kidney impairment.

Effects of renal denervation on kidney function in patients with chronic kidney disease: a systematic review and meta-analysis.

The present study aims to evaluate the clinical outcomes following renal denervation (RDN) for hypertensive patients with chronic kidney disease (CKD). Prospective studies published between January 1, 2010 and November 15, 2022 where systematically identified for RDN outcomes on office and ambulatory blood pressure, estimated glomerular filtration rate (eGFR), creatinine and procedural characteristics from three online databases (Medline, PubMed, EMBASE). Random effects model to combine risk ratios and mean differences was used. Where possible, clinical outcomes were pooled and analyzed at 6, 12 and 24 months. Significance was set at p ≤ 0.05. 11 prospective trials, with a total of 226 patients with treatment resistant HTN receiving RDN met the inclusion criteria. Age ranged from 42.5 ± 13.8 to 66 ± 9. Main findings of this review included a reduction in systolic and diastolic office blood pressure at 6 [-19.8 (p < 0.00001)/-15.2 mm Hg (p < 0.00001)] and 12 months [-21.2 (p < 0.00001)/-9.86 mm Hg (p < 0.0005)] follow-up compared to baseline. This was also seen in systolic and diastolic 24-hour ambulatory blood pressure at 6 [-9.77 (p = 0.05)/-3.64 mm Hg (p = 0.09)] and 12 months [-13.42 (p = 0.0007)/-6.30 mm Hg (p = 0.001)] follow-up compared to baseline. The reduction in systolic and diastolic 24-hour ambulatory blood pressure was maintained to 24 months [(-16.30 (p = 0.0002)/-6.84 mm Hg (p = 0.0010)]. Analysis of kidney function through eGFR demonstrated non-significant results at 6 (+1.60 mL/min/1.73 m2, p = 0.55), 12 (+5.27 mL/min/1.73 m2, p = 0.17), and 24 months (+7.19 mL/min/1.73 m2, p = 0.36) suggesting an interruption in natural CKD progression. Similar results were seen in analysis of serum creatinine at 6 (+0.120 mg/dL, p = 0.41), 12 (+0.100 mg/dL, p = 0.70), and 24 months (+0.07 mg/dL, p = 0.88). Assessment of procedural complications deemed RDN in a CKD cohort to be safe with an overall complication rate of 4.86%. With the current advances in RDN and its utility in multiple chronic diseases beyond hypertension, the current study summarizes critical findings that further substantiate the literature regarding the potential of such an intervention to be incorporated as an effective treatment for resistant hypertension and CKD.

Bilateral Cardiac Sympathetic Denervation for Refractory Multifocal Premature Ventricular Contractions in Patients With Nonischemic Cardiomyopathy.

BACKGROUND: Bilateral cardiac sympathetic denervation (BCSD) for refractory life-threatening ventricular arrhythmias is a neuromodulatory intervention targeting sympathetically driven focal or re-entrant ventricular arrhythmias. OBJECTIVES: This study sought to provide a more complete and successful option for intervention in patients in whom premature ventricular contraction (PVC) ablation is not feasible or has been unsuccessful. METHODS: A total of 43 patients with >5% PVC burden and concomitant nonischemic cardiomyopathy (NICM) who previously failed medical and ablation therapies were referred for BCSD. All patients underwent bilateral video-assisted thoracoscopic surgical approach with T1-T4 sympathectomy. Primary effectiveness endpoints were postprocedural PVC burden resolution, improvement in left ventricular ejection fraction (LVEF), and cessation of antiarrhythmic drugs (AADs). Safety endpoints included peri- and postprocedural complications. Outcomes were assessed over a 1-year follow-up period. RESULTS: Among the 43 patients who underwent BCSD, the mean age was 52.3 ± 14.7 years, 69.8% of whom were male patients. Presenting mean LVEF was 38.7% ± 7.8%, and PVC burden was 23.7% ± 9.9%. There were significant reductions in PVC burden postprocedurally (1.3% ± 1.1% post-BCSD, compared with 23.7% ± 9.9% pre-BCSD, P < 0.001) and improvements in LVEF (46.3% ± 9.5% post-BCSD, compared with 38.7% ± 7.8% pre-BCSD, P < 0.001). The rate of ICD therapies decreased from 81.4% (n = 35) to 11.6% (n = 5) (P < 0.001), leading to a significant reduction in use of AADs (100.0% to 11.6%, P < 0.001) and improvement in mean NYHA functional class (2.5 ± 0.5 to 1.4 ± 0.2, P < 0.001). Major intraoperative complications were seen in 4.7% of patients (hemothorax and chylothorax). Of the patients, 81.4% (n = 35) experienced no mortality or major complications over a 1-year follow-up period, with the remaining still within their first year postprocedure. CONCLUSIONS: BCSD is effective for the management of refractory PVCs and ventricular tachycardia who have failed previous ablation therapy.

A multicentre retrospective study of lumbar sympathectomy for plantar hyperhidrosis: satisfaction and postoperative complications.

BACKGROUND: Primary plantar hyperhidrosis has a severe impact on quality of life and conservative treatments are only effective in the short term. Thoracic sympathectomy has proven its effectiveness in the treatment of palmar hyperhidrosis, but lumbar sympathectomy for plantar hyperhidrosis remains poorly described. OBJECTIVES: To report the satisfaction of patients with primary plantar hyperhidrosis treated with mechanical lumbar sympathectomy as well as their postoperative complications. METHODS: This was a multicentre retrospective observational study of 16 patients with primary plantar hyperhidrosis, treated with mechanical lumbar sympathectomy from December 2012 to October 2022. Patients' characteristics were collected from medical records. Quality of life, postoperative satisfaction and complications were evaluated using a standardized questionnaire. RESULTS: Lumbar sympathectomy was performed on 16 patients, 14 were women and 2 were men with a total of 31 procedures. Fourteen (88%) patients were satisfied and would recommend the surgery to other patients. Compensatory hyperhidrosis occurred in 75% of patients, recurrence of hyperhidrosis in 31% and sexual dysfunction in 19%. CONCLUSIONS: Lumbar sympathectomy provides satisfying results for plantar hyperhidrosis with acceptable postoperative complications, regardless of sex. Compensatory hyperhidrosis was the most frequent complication but had no impact on patient satisfaction. In the literature, data on the risk of sexual dysfunction are reassuring and in our study only one of two men experienced transient ejaculation disorder.

The role of renal denervation in cardiology and beyond: An updated comprehensive review and future directives.

Renal denervation (RDN) is a minimally invasive intervention performed by denervation of the nervous fibers in the renal plexus, which decreases sympathetic activity. These sympathetic nerves influence various physiological functions that regulate blood pressure (BP), including intravascular volume, electrolyte composition, and vascular tone. Although proven effective in some trials, controversial trials, such as the Controlled Trial of Renal Denervation for Resistant Hypertension (SYMPLICITY-HTN3), have demonstrated contradictory results for the effectiveness of RDN in resistant hypertension (HTN). In the treatment of HTN, individuals with primary HTN are expected to experience greater benefits compared to those with secondary HTN due to the diverse underlying causes of secondary HTN. Beyond its application for HTN, RDN has also found utility in addressing cardiac arrhythmias, such as atrial fibrillation, and managing cases of heart failure. Non-cardiogenic applications of RDN include reducing the intensity of obstructive sleep apnea (OSA), overcoming insulin resistance, and in chronic kidney disease (CKD) patients. This article aims to provide a comprehensive review of RDN and its uses in cardiology and beyond, along with providing future directions and perspectives.

Skin sodium content as a predictor of blood pressure response to renal denervation.

Patients with treatment resistant hypertension (TRH) are known to have elevated sodium (Na) content in muscle and skin. Renal denervation (RDN) emerged as an adjacent therapeutic option in this group of patients. This analysis aimed at evaluating whether tissue Na content predicts blood pressure (BP) response after RDN in patients with TRH. Radiofrequency-device based RDN was performed in 58 patients with uncontrolled TRH. Office and 24-h ambulatory BP were measured at baseline and after 6 months. To assess tissue Na content Na magnetic resonance imaging (Na-MRI) was performed at baseline prior to RDN. We splitted the study cohort into responders and non-responders based on the median of systolic 24-h ambulatory blood pressure (ABP) reduction after 6 months and evaluated the association between BP response to RDN and tissue Na content in skin and muscle. The study was registered at http://www.clinicaltrials.gov (NCT01687725). Six months after RDN 24-h ABP decreased by -8.6/-4.7 mmHg. BP-Responders were characterized by the following parameters: low tissue sodium content in the skin (p = 0.040), female gender (p = 0.027), intake of aldosterone antagonists (p = 0.032), high baseline 24-h night-time heart rate (p = 0.045) and high LDL cholesterol (p < 0.001). These results remained significant after adjustment for baseline 24-h systolic BP. Similar results were obtained when the median of day-time and night-time ABP reduction after 6 months were used as cut-off criteria for defining BP response to RDN. We conclude that in addition to clinical factors including baseline 24-h ABP Na-MRI may assist to select patients with uncontrolled TRH for RDN treatment.

Patient-Level Pooled Analysis of Endovascular Ultrasound Renal Denervation or a Sham Procedure 6 Months After Medication Escalation: The RADIANCE Clinical Trial Program.

BACKGROUND: The randomized, sham-controlled RADIANCE-HTN (A Study of the Recor Medical Paradise System in Clinical Hypertension) SOLO, RADIANCE-HTN TRIO, and RADIANCE II (A Study of the Recor Medical Paradise System in Stage II Hypertension) trials independently met their primary end point of a greater reduction in daytime ambulatory systolic blood pressure (SBP) 2 months after ultrasound renal denervation (uRDN) in patients with hypertension. To characterize the longer-term effectiveness and safety of uRDN versus sham at 6 months, after the blinded addition of antihypertensive treatments (AHTs), we pooled individual patient data across these 3 similarly designed trials. METHODS: Patients with mild to moderate hypertension who were not on AHT or with hypertension resistant to a standardized combination triple AHT were randomized to uRDN (n=293) versus sham (n=213); they were to remain off of added AHT throughout 2 months of follow-up unless specified blood pressure (BP) criteria were exceeded. In each trial, if monthly home BP was ≥135/85 mm Hg from 2 to 5 months, standardized AHT was sequentially added to target home BP <135/85 mm Hg under blinding to initial treatment assignment. Six-month outcomes included baseline- and AHT-adjusted change in daytime ambulatory, home, and office SBP; change in AHT; and safety. Linear mixed regression models using all BP measurements and change in AHT from baseline through 6 months were used. RESULTS: Patients (70% men) were 54.1±9.3 years of age with a baseline daytime ambulatory/home/office SBP of 150.5±9.8/151.0±12.4/155.5±14.4 mm Hg, respectively. From 2 to 6 months, BP decreased in both groups with AHT titration, but fewer uRDN patients were prescribed AHT (P=0.004), and fewer additional AHT were prescribed to uRDN patients versus sham patients (P=0.001). Whereas the unadjusted between-group difference in daytime ambulatory SBP was similar at 6 months, the baseline and medication-adjusted between-group difference at 6 months was -3.0 mm Hg (95% CI, -5.7, -0.2; P=0.033), in favor of uRDN+AHT. For home and office SBP, the adjusted between-group differences in favor of uRDN+AHT over 6 months were -5.4 mm Hg (-6.8, -4.0; P<0.001) and -5.2 mm Hg (-7.1, -3.3; P<0.001), respectively. There was no heterogeneity between trials. Safety outcomes were few and did not differ between groups. CONCLUSIONS: This individual patient-data analysis of 506 patients included in the RADIANCE trials demonstrates the maintenance of BP-lowering efficacy of uRDN versus sham at 6 months, with fewer added AHTs. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02649426 and NCT03614260.

Endoscopic Thoracic Sympathectomy in the Treatment of Vasospastic Angina Resistant to Medical Therapy.

BACKGROUND: In this study, we aimed to investigate the clinical follow-up results of endoscopic thoracic sympathectomy (ETS) in the treatment of vasospastic angina (VSA) resistant to maximal medical therapy. METHODS: A total of 80 patients with VSA who presented to our hospital between 2010 and 2022 were included in our study. Among them, 6 patients who did not respond to medical therapy underwent ETS. In-hospital and long-term clinical outcomes of patients who underwent ETS were recorded. RESULTS: The median age of the patients with VSA was 57 [48-66] years, and 70% of the group were males. In the ETS group, compared to the non-ETS group, higher numbers of hospital admissions and coronary angiographies were observed before ETS (median 6 [5-6] versus 2 [1-3], P <.001; median 5 [3-6] versus 2 [1-3], P =.004, respectively). Additionally, while 2 patients (33.3%) in the ETS group had implantable cardioverter defib-rillator (ICD), only 2 patients (2.7%) in the non-ETS group had ICD (P =.027). Out of the 6 patients who underwent ETS, 2 were females, with a median age of 56 [45-63] years. Four patients underwent successful bilateral ETS, while 2 patients underwent unilateral ETS. During the follow-up period after ETS, only 3 patients experienced sporadic attacks (once in 28 months, twice in 41 months, and once in 9 years, respectively), while no attacks were observed in 3 patients during their median follow-up of 7 years. CONCLUSION: It appears that ETS is effective in preventing VSA attacks without any major complications.

Renal Denervation in the Treatment of Resistant Hypertension and Difficult-to-Control Hypertension - Consensus Document of the Croatian Hypertension League - Croatian Society of Hypertension, Croatian Cardiac Society, Croatian Endovascular Initiative, Croatian Society for Diabetes and Metabolic Diseases, Croatian Renal Association, and Croatian Society of Family Physicians of the Croatian Medical Association.

Renal denervation (RDN) as a method of treating arterial hypertension (AH) was introduced in Croatia in 2012. A multidisciplinary team and a network of hospitals that diagnose and treat patients with severe forms of AH were established, and a very strict diagnostic-treatment algorithm was prepared. At monthly meetings patients with truly resistant hypertension who were candidates for RDN were discussed. According to the 2021 ESH position statement and 2023 ESH guidelines, RDN is considered an alternative and additional, not a competitive method of treating patients with various forms of AH which must be performed by following a structured procedure and the patient's preference should be considered. In view of the changes in the global scientific community, the Croatian Hypertension League brings this consensus document on RDN conducted with radiofrequency-based catheter, the only currently available method in Croatia. In this document, exclusion and inclusion criteria are shown, as well as three groups of patients in whom RDN could be considered. The new diagnostic-treatment algorithm is prepared and follow-up procedure is explained. In Croatia, RDN is reimbursed by the national insurance company, thus pharmacoeconomic analyses is also shown. Criteria required by an individual centre to be approved of RDN are listed, and plans for prospective research on RDN in Croatia, including the Croatian registry for RDN, are discussed.

[Five-year dynamics adrenergic reactivity of erythrocytes after radio-frequency sympathic denervation of renal arteries in patients with resistant arterial hypertension].

AIM: To study the initial state of adrenergic reactivity and the five-year dynamics of the beta-adrenergic reactivity index of erythrocyte membranes and the manifestation of the antihypertensive effect of the procedure for radiofrequency destruction of sympathetic structures of the renal artery in patients with resistant arterial hypertension. SUBJECTS AND METHODS: The analysis included 42 patients with resistant arterial hypertension (RH). The renal denervation (RD) procedure of the kidneys was performed by endovascular bilateral transcatheter radiofrequency ablation of the renal arteries. The study of 24-hour blood pressure monitoring (BPM) and the determination of ß-adrenoreactivity of erythrocytes (ß-ARM) by changes in the osmoresistance of erythrocyte membranes were performed initially, 1 week, 6 months, 1, 2, 3 and 5 years after RD. Patients retrospectively, at a follow-up period of 6 months after RD, were divided into responders (decrease in blood pressure by 10 or more mm Hg) and non-responders (decrease in blood pressure less than 10 mm Hg). RESULTS: 6 months after the RD, the number of responders was 28 people (66.7%), after 5 years - 31 people (73.8%). At the time of inclusion in the study, the median ß-ARM in the group of non-responders was not significantly higher than in the group of responders. After 6 months after the RD procedure, the ß-ARM indicator in the non-responder group was significantly lower than in the responder group (p = 0.043). With further follow-up in the group of responders, an increase in the median ß-ARM was noted, which reached significant differences relative to the baseline values in the group at follow-up periods of 1 year (p = 0.036) and 5 years (p = 0.004) after RD. The change in the ß-ARM indicator in the non-responder group was wavy in nature, the changes did not reach the significance criteria. CONCLUSION: Renal denervation in 73.8% of cases is accompanied by a stable antihypertensive response for 5 years of observation and an increase in ß-ARM, which may indicate the implementation of compensatory mechanisms in conditions of increasing activity of the sympathoadrenal system in response to a decrease in blood pressure.