Renal Denervation Group Research Articles

Assessing the efficacy of renal denervation in patients with resistant arterial hypertension: a systematic review and meta-analysis

Abstract Background/Introduction Renal denervation (RDN) is an innovative procedure designed to regulate the renal sympathetic nervous system for the control of arterial hypertension (HTN). RDN emerges as an alternative for patients with resistant arterial hypertension. Despite this, the clinical efficacy of RDN is still not fully understood. Purpose Therefore, we aimed to compare the use of renal denervation versus sham procedure or pharmacological treatment in patients with resistant HTN. Methods We performed a systematic search of PubMed, Embase, Cochrane databases for randomized controlled trials (RCTs) comparing the use of renal denervation procedures and sham procedure or pharmacological treatment in patients with resistant HTN. Statistical analyses were performed using R Studio 4.3.2. Heterogeneity was examined with the Cochran Q test I² statistics. Mean difference (MD) with 95% CI were pooled across trials. P values of < 0.05 were considered statistically significant. The primary continuous outcomes of interest were change from baseline in systolic blood pressure (SBP), diastolic blood pressure (DBP) and serum creatinine. Results Twenty-one RCTs reporting data on 3345 patients were included in this meta-analysis. Among them, 2004 (59,91%) received renal denervation and 1341 (40,09%) received pharmacological treament or sham procedure. Follow-up ranged from 2 to 48 months. The mean age of patients between studies ranged from 50.7 to 65 years. Compared to control group, RDN significantly reduced Systolic Blood Pressure (SBP) (MD -3.53 mmHg; 95% CI -5.94 to -1.12; I2 = 74%) and Diastolic Blood Pressure (DBP) (MD -1.48 mmHg; 95% CI -2.56 to -0.40; I2 = 51%). Regarding serum creatinine (MD -2.51; 95% CI -7.90 to 2.87; I2 = 40%) there was no significant difference between RDN and control groups. Conclusion In this meta-analysis of RCTs of patients with resistant HTN, RDN was associated with a reduction in SBP and DBP compared to sham procedure or pharmacological treatment.

Effects of Catheter-Based Renal Denervation in Hypertension: A Systematic Review and Meta-Analysis.

Several sham-controlled trials have investigated the efficacy and safety of catheter-based renal denervation (RDN) with mixed outcomes. We aimed to perform a comprehensive meta-analysis of all randomized, sham-controlled trials investigating RDN with first- and second-generation devices in hypertension. We searched MEDLINE and the Cochrane Library for eligible trials. Outcomes included both efficacy (24-hour and office systolic [SBP] and diastolic blood pressure [DBP]) and safety (all-cause death, vascular complication, renal artery stenosis >70%, hypertensive crisis) of RDN. We performed a study-level, pairwise, random-effects meta-analysis of the summary data. Ten trials comprising 2478 patients with hypertension while being either off or on treatment were included. Compared with sham, RDN reduced 24-hour and office systolic blood pressure by 4.4 mm Hg (95% CI, 2.7 to 6.1; P<0.00001) and 6.6 mm Hg (95% CI, 3.6 to 9.7; P<0.0001), respectively. The 24-hour and office diastolic blood pressure paralleled these findings (-2.6 mm Hg [95% CI, -3.6 to -1.5]; P<0.00001; -3.5 mm Hg [95% CI, -5.4 to -1.6]; P=0.0003). There was no difference in 24-hour and office systolic blood pressure reduction between trials with and without concomitant antihypertensive medication (P for interaction, 0.62 and 0.73, respectively). There was no relevant difference in vascular complications (odds ratio, 1.69 [95% CI, 0.57 to 5.0]; P=0.34), renal artery stenosis (odds ratio, 1.50 [95% CI, 0.06 to 36.97]; P=0.80), hypertensive crisis (odds ratio, 0.65 [95% CI, 0.30 to 1.38]; P=0.26), and all-cause death (odds ratio, 1.76 [95% CI, 0.34 to 9.20]; P=0.50) between RDN and sham groups. Change of renal function based on estimated glomerular filtration rate was comparable between groups (P for interaction, 0.84). There was significant heterogeneity between trials. RDN safely reduces ambulatory and office systolic blood pressure/diastolic blood pressure versus a sham procedure in the presence and absence of antihypertensive medication.

Effects of bilateral renal denervation on open-loop baroreflex function and urine excretion in spontaneously hypertensive rats.

Bilateral renal denervation (RDN) decreases arterial pressure (AP) or delays the development of hypertension in spontaneously hypertensive rats (SHR), but whether bilateral RDN significantly modifies urine output function during baroreflex-mediated acute AP changes remains unknown. We quantified the relationship between AP and normalized urine flow (nUF) in SHR that underwent bilateral RDN (n = 9) and compared the results with those in sham-operated SHR (n = 9). Moreover, we examined the acute effect of an angiotensin II type 1 receptor blocker telmisartan (2.5 mg/kg) on the AP-nUF relationship. Bilateral RDN significantly decreased AP by narrowing the response range of the total arc of the carotid sinus baroreflex. The slopes of nUF versus the mean AP (in μL·min-1·kg-1·mmHg-1) in the sham and RDN groups under baseline conditions were 0.076 ± 0.045 and 0.188 ± 0.039, respectively; and those after telmisartan administration were 0.285 ± 0.034 and 0.416 ± 0.078, respectively. The effect of RDN on the nUF slope was marginally significant (P = 0.059), which may have improved the controllability of urine output in the RDN group. The effect of telmisartan on the nUF slope was significant (P < 0.001) in the sham and RDN groups, signifying the contribution of circulating or locally produced angiotensin II to determining urine output function regardless of ongoing renal sympathetic nerve activity.

Assessing the efficacy of renal denervation in patients with resistant arterial hypertension : Systematic review and meta-analysis.

Renal denervation (RDN) is an innovative procedure designed to regulate the renal sympathetic nervous system for the control of arterial hypertension (HTN). RDN has emerged as an alternative for patients with resistant HTN. However, the clinical efficacy of RDN remains incompletely elucidated. PubMed, Embase, and Cochrane databases were searched for randomized controlled trials (RCTs) comparing the use of RDN with sham procedure or pharmacological treatment in patients with resistant HTN. Statistical analyses were performed using RStudio 4.3.2 (R Foundation for Statistical Computing, Vienna, Austria). Heterogeneity was examined with the CochranQ testI2 statistics. Mean difference (MD) with 95% confidence interval (CI) were pooled across trials. Pvalues of <0.05 were considered statistically significant. The primary outcomes of interest were changes from baseline in systolic blood pressure (SBP), diastolic blood pressure (DBP), and serum creatinine. Twenty-one RCTs comprising 3345 patients were included in this meta-analysis, whereby 2004 (59.91%) received renal denervation and 1341 (40.09%) received pharmacological treatment or sham procedure. Follow-up ranged from 2to 48months. Compared to control group, RDN significantly reduced SBP (MD -3.53 mm Hg; 95% CI -5.94 to -1.12; p = 0.004; I2 = 74%) and DBP (MD -1.48 mm Hg; 95% CI -2.56 to -0.40; p = 0.007; I2 = 51%). Regarding serum creatinine (MD -2.51; 95% CI -7.90 to 2.87; p = 0.36; I2 = 40%), there was no significant difference between RDN and control groups. In this meta-analysis of RCTs of patients with resistant HTN, RDN was associated with areduction in SBP and DBP compared to sham procedure or pharmacological treatment.

Efficacy and Safety of Catheter-Based Radiofrequency Renal Denervation in Chinese Patients With Uncontrolled Hypertension: The Randomized, Sham-Controlled, Multi-Center Iberis-HTN Trial.

Renal denervation (RDN) can lower blood pressure (BP) in patients with hypertension in both the presence and absence of medication. This is the first sham-controlled trial investigating the safety and efficacy of RDN in China. This prospective, multicenter, randomized, patient- and outcome-assessor-blinded, sham-controlled trial investigated radiofrequency RDN in patients with hypertension on standardized triple antihypertensive therapy. Eligible patients were randomized 1:1 to undergo RDN using a multi-electrode radiofrequency catheter (Iberis; AngioCare, Shanghai, China) or a sham procedure. The primary efficacy outcome was the between-group difference in baseline-adjusted change in mean 24-hour ambulatory systolic BP from randomization to 6 months. Of 217 randomized patients (mean age, 45.3±10.2 years; 21% female), 107 were randomized to RDN and 110 were randomized to sham control. At 6 months, there was a greater reduction in 24-hour systolic BP in the RDN (-13.0±12.1 mm Hg) compared with the sham control group (-3.0±13.0 mm Hg; baseline-adjusted between-group difference, -9.4 mm Hg [95% CI, -12.8 to -5.9]; P<0.001). Compared with sham, 24-hour diastolic BP was lowered by -5.0 mm Hg ([95% CI, -7.5 to -2.4]; P<0.001) 6 months after RDN, and office systolic and diastolic BP was lowered by -6.4 mm Hg ([95% CI, -10.5 to -2.3]; P=0.003) and -5.1 mm Hg ([95% CI, -8.2 to -2.0]; P=0.001), respectively. One patient in the RDN group experienced an access site complication (hematoma), which resolved without sequelae. No other major device- or procedure-related safety events occurred through follow-up. In this trial of Chinese patients with uncontrolled hypertension on a standardized triple pharmacotherapy, RDN was safe and reduced ambulatory and office BP at 6 months compared with sham. URL: https://clinicaltrials.gov; Unique identifier: NCT02901704.

What are the ideal metrics for assessing the quality of long-term stabilized "perfect" 24-h BP control after renal denervation?

A significant number of individuals being treated for hypertension still have uncontrolled blood pressure (BP). In Japan, renal denervation (RDN) is being introduced into clinical practice as an adjunctive treatment for hypertension that is uncontrolled despite adequate lifestyle changes and maximal antihypertensive drug therapy. The pivotal SPYRAL ON-MED trial showed that there was a significant reduction in trough office and nighttime ambulatory BP values in the RDN group compared with sham control group, although 24-h and daytime BP values were not significantly different between the two groups. The trough office BP measurement (taken before morning antihypertensive dosing) is similar to guideline recommendations for taking morning home BP before taking the morning antihypertensive drug dose. Recent guidelines recommend the measurement of nighttime BP because nighttime BP is a stronger predictor of cardiovascular event risk than daytime BP. It is particularly important to assess nighttime BP in medicated individuals with hypertension because the up- or down-titration of antihypertensive drug dosing is primarily based on office and daytime BPs in clinical practice. This means that there may be significant risk relating to nocturnal hypertension during longer follow-up. Because RDN results in persistent, "always-on" 24-h BP-lowering effects, the best BP metrics to assess the potential benefit of RDN are nighttime BP (determined using home or ambulatory BP monitoring) and morning BP (determined using home BP monitoring or morning trough office BP measurement). The variability of office, home, and ambulatory BP values is another important metric to assess the quality of RDN-related BP lowering.

Effects of catheter-based renal denervation in hypertension: a systematic review and meta-analysis.

Several sham-controlled trials have investigated the efficacy and safety of catheter-based renal denervation (RDN) with mixed outcomes. To perform a comprehensive meta-analysis of all randomized, sham-controlled trials investigating RDN with first- and second-generation devices in hypertension. We searched MEDLINE and Cochrane Library for eligible trials. Outcomes included both efficacy (24-hour and office systolic [SBP] and diastolic blood pressure [DBP]) and safety (all-cause death, vascular complication, renal artery stenosis >70%, hypertensive crisis) of RDN. We performed a study-level, pairwise, random-effects meta-analysis of the summary data. Ten trials comprising 2,478 patients with hypertension while being either off- or on-treatment were included. Compared with sham, RDN reduced 24-hour and office systolic BP by 4.4 mmHg (95%CI -6.1, -2.7, p<0.00001) and 6.6 mmHg (95%CI -9.7, -3.6, p<0.0001), respectively. The 24-hour and office diastolic BP paralleled these findings (-2.6 mmHg, 95%CI - 3.6, -1.5, p<0.00001; -3.5 mmHg, 95%CI -5.4, -1.6, p=0.0003). There was no difference in 24-hour and office SBP reduction between trials with and without concomitant antihypertensive medication (p for interaction 0.62 and 0.73, respectively). There was no relevant difference concerning vascular complications (OR 1.69, 95%CI 0.57-5.0, p=0.34), renal artery stenosis (OR 1.50, 95%CI 0.06-36.97, p=0.80), hypertensive crisis (OR 0.65, 95%CI 0.30-1.38, p=0.26) and all-cause death (OR 1.76, 95%CI 0.34-9.20, p=0.50) between RDN and sham groups. Change of renal function based on eGFR was comparable between groups (p for interaction 0.84). There was significant heterogeneity between trials. RDN safely reduces ambulatory and office SBP/DBP vs. a sham procedure in the presence and absence of antihypertensive medication. What is new?Several sham-controlled trials have investigated the efficacy and safety of catheter-based renal denervation (RDN) with mixed outcomes.This comprehensive meta-analysis comprising 2,478 patients shows that irrespective of the utilized method (radiofrequency-, ultrasound-or alcohol-mediated), renal denervation effectively reduced ambulatory and office systolic blood pressure.Renal denervation exhibited no additional risk concerning vascular injury or renal function impairment.What are the clinical implications?This meta-analysis supports current guidelines/consensus statements that renal denervation represents an additive treatment option in carefully selected patients with uncontrolled hypertension.

Is Renal Denervation Effective in Treating Resistant Hypertension?

Resistant hypertension is diagnosed in patients whose blood pressure target is unmet despite the use of three or more antihypertensive medications. Systemic sympathetic hyperactivation is associated with the development of resistant hypertension. As the kidney is largely pervasive of the sympathetic nervous system renal denervation procedure was developed to control blood pressure by attenuating the renal and systemic sympathetic hyperactivity. Renal denervation is a minimally invasive procedure that uses radiofrequency or ultrasound energy waves to reduce the activity of the renal artery nerves. Previous clinical trials have shown conflicting results regarding the efficacy of the procedure. Symplicity HTN-1 and -2 trials showed effective blood pressure lowering results in the renal denervation group with a good safety profile. However, the Symplicity HTN-3 trial showed no difference in blood pressure lowering effect between the renal denervation and control Sham procedure groups. Notwithstanding, some recent clinical trials with Sham control and meta-analysis showed clinical benefits of renal denervation. Other clinical benefits of renal denervation include glucose control, cardiovascular protective effect, reduction of obstructive sleep apnea, and neuralgia control. A subset of patients with satisfactory blood pressure control response to the procedure may experience improved glucose control due to the overall reduced sympathetic activity and insulin resistance. Sympathetic activity control after renal denervation has cardioprotective effects, especially for those with arrhythmia and left ventricular hypertrophy. Also, renal denervation could be helpful in renalorigin pain control. Renal denervation is an effective, safe, non-invasive procedure with many clinical benefits beyond blood pressure control. Further development in the procedure technique and selection of target patients are needed for wider clinical use of renal denervation in resistant hypertension.

TEN YEAR FOLLOW-UP OF PATIENTS WITH RESISTANT HYPERTENSION RANDOMIZED TO RENAL DENERVATION OR ANTIHYPERTENSIVE DRUG TREATMENT

Objective: Renal denervation (RDN) is a treatment option in resistant hypertension. The procedure is considered safe, although randomized trials only demonstrate a moderate blood pressure (BP) lowering effect, when considering medication adherence. Some observational studies describe reduction in BP several years after the procedure. The aim of the study was to describe long-term safety and potential benefits of RDN after ten years, compared to optimized drug treatment, measuring serum concentration of antihypertensive drugs to ensure adherence. Design and method: We report data from ten year follow-up of patients randomized to RDN (n=9) or drug adjustment (n=10). Initially the patients had treatment-resistant hypertension, defined as daytime systolic ambulatory BP &gt;= 135 mmHg after witnessed intake (directly observed therapy, DOT) of &gt;= 3 antihypertensive drugs including a diuretic and therefore considered as adherent. One year after RDN or drug adjustment, we optimized antihypertensive medication for all patients. Thereafter, patients received appropriate antihypertensive treatment in primary or secondary care, according to their BPs. Patients were informed of serum concentration measurements performed at the 7-year visit. At the 10-year visit, serum drug measurements before DOT and ambulatory BP measurement (ABPM) were used for evaluation of adherence. Antihypertensive agents were registered, glomerular filtration rate (eGFR) was estimated by the CKD-EPI formula using creatinine and Cystatin C, and renal arteries were examined by CT or MRI. Results: All living patients (n=18) attended the 10-year visit, now mean age 69 years, using 4±2 antihypertensive agents, with no difference between groups. Serum concentrations confirmed that all patients were adherent to reported medication. There were significant and similar BP reductions in both groups compared to baseline; daytime ABPM -22±15/9±8 mmHg in the RDN group, and -20±15/13±7 mmHg in the control group (figure). No patients developed renal artery stenosis. The decrease in eGFR was similar in both groups. Conclusions: To our knowledge this is the RCT with the longest follow-up supporting long-term safety of RDN in patients with resistant hypertension. Daytime ABPM improved during 10 years of follow-up, not explained by RDN, but due to adjustments in antihypertensive regimens and probably better adherence to medication.

Effect of Alcohol-Mediated Renal Denervation on Blood Pressure in the Presence of Antihypertensive Medications: Primary Results from the TARGET BP I Randomized Clinical Trial.

Renal denervation (RDN) has demonstrated clinically relevant reductions in blood pressure among individuals with uncontrolled hypertension despite lifestyle intervention and medications. The safety and effectiveness of alcohol-mediated RDN has not been formally studied in this indication. TARGET BP I is a prospective, international, sham-controlled, randomized, patient- and assessor-blinded trial investigating the safety and efficacy of alcohol-mediated RDN. Patients with office systolic blood pressure (SBP) ≥150 and ≤180 mmHg, office diastolic BP ≥90 mmHg and mean 24-hour ambulatory SBP ≥135 and ≤170 mmHg, despite prescription of 2-5 antihypertensive medications were enrolled. The primary endpoint was the baseline-adjusted change in mean 24-hour ambulatory systolic BP at 3 months post procedure. Secondary endpoints include mean between-group differences in office and ambulatory BP at additional time points. Among 301 patients randomized 1:1 to RDN or sham control, RDN was associated with a significant reduction in 24-hour ambulatory SBP at 3 months (mean ± standard deviation -10.0 ± 14.2 mmHg versus -6.8 ± 12.1 mmHg, treatment difference -3.2 mmHg, 95% confidence interval [CI] -6.3, 0.0 mmHg; P=0.0487). Subgroup analysis of the primary endpoint revealed no significant interaction across predefined subgroups. At 3 months, the mean change in office SBP was -12.7 ± 18.3 mmHg and -9.7 ± 17.3 mmHg (difference, -3.0, 95% CI -7.0, 1.0; P=0.173), for RDN and sham, respectively. No significant differences in ambulatory or office diastolic BP were observed. Adverse safety events through 6 months were uncommon with 1 instance of accessory renal artery dissection in the RDN group (0.7%). No significant between-group differences in medication changes or patient adherence were identified. Alcohol-mediated RDN was associated with a modest but statistically significant reduction in 24-hour ambulatory systolic BP compared with sham control. No significant differences between groups in office BP or 6-month major adverse events were observed.

The effects of renal denervation on blood pressure, cardiac hypertrophy, and sympathetic activity during the established phase of hypertension in spontaneously hypertensive rats.

This study aimed to investigate whether renal denervation (RDN) reduces blood pressure and attenuates cardiac hypertrophy with decreasing sympathetic activity in spontaneously hypertensive rats (SHRs), a model of essential hypertension, during the established phase of hypertension. We performed RDN or sham operation in 15-weeks-old SHRs. Thirty days after RDN, mean blood pressure measured by telemetry, heart weight, left ventricular wall thickness assessed by echocardiography, and urinary norepinephrine levels were significantly decreased in the RDN group compared to the Sham group. Furthermore, oxidative stress, as indicated by thiobarbituric acid reactive substances, in the rostral ventrolateral medulla, a pivotal region regulating basal sympathetic tone, was significantly decreased in the RDN group. In conclusion, RDN reduces blood pressure and attenuates cardiac hypertrophy with sympathoinhibition in the established phase of hypertension in SHRs. These findings highlight the sympathoinhibitory effect of RDN and suggest that RDN may be a potential therapy for hypertensive cardiac hypertrophy. Renal denervation reduces blood pressure and attenuates cardiac hypertrophy with sympathoinhibition in the established phase of hypertension in spontaneously hypertensive rats. This study highlights the sympathoinhibitory effect of renal denervation and suggests that renal denervation may be a potential therapy for hypertensive cardiac hypertrophy.

Effects of Renal Denervation on Ouabain‐Induced Hypertension in Rats

Background. Ouabain, a Na+, K+‐ATPase inhibitor, is elevated in hypertensive patients. Evidence suggests ouabain contributes to hypertension mainly through activation of the sympathetic nervous system (SNS). Renal nerves play a vital role in the regulation of SNS activity, so we hypothesize that renal denervation may attenuate the development of ouabain‐induced hypertension. Methods and Results. Forty Sprague‐Dawley rats were divided into following groups (n = 10 each): control group (sham surgery plus intraperitoneal saline injection), RDN group (renal denervation (RDN) plus intraperitoneal saline injection), ouabain group (sham surgery plus intraperitoneal ouabain injection), and ouabain + RDN group (RDN plus intraperitoneal ouabain injection). After eight weeks, compared with the control group, rats in the ouabain group exhibited elevated blood pressure (P &lt; 0.05), increased plasma epinephrine, norepinephrine, angiotensin II, and aldosterone levels (P &lt; 0.05). These indexes could be significantly ameliorated by RDN. RDN also reduced the thickening of aortic tunica media and downregulated the expression of proliferating cell nuclear antigen (PCNA) in the thoracic aorta induced by ouabain. Masson staining and echocardiography showed that myocardial fibrosis and increased left ventricular mass in the ouabain group could be attenuated by RDN. Conclusions. The present study reveals that renal nerves play an important role in the development of ouabain‐induced hypertension. RDN could inhibit the pressor effect and the myocardial remodeling induced by ouabain potentially via inhibiting catecholamine release and vascular smooth muscle cell proliferation. Clinical studies are needed to explore whether RDN may exhibit better antihypertensive effects on hypertensive patients with high plasma ouabain levels as compared to those with normal plasma ouabain levels.

Effect of Renal Sympathetic Denervation on Ventricular Electrical Activity in Myocardial Infarction.

Coronary artery blockage causes myocardial infarction (MI), a frequent and serious cardiovascular disease. The early recurrence of post-MI ventricular fibrillation after defibrillation has been widely investigated and treated. This research investigated the relationship between electrophysiological indicators of early recurrence following defibrillation in post-MI ventricular fibrillation and sympathetic renal denervation's therapeutic benefits and probable causes. Animal models were used for experiments. Electrophysiological indications of early recurrence were reported after MI and defibrillation in ventricular fibrillation patients. After that, a selection of rats received sympathetic renal denervation, and the therapeutic results were compared to the control group. Electrocardiogram monitoring, myocardial histology, and neurotransmitter assays were done. Defibrillation therapy causes an early recurrence in ventricular fibrillation patients. Electrophysiological measures showed increased ST segment elevation and T wave alterations in the early recurrence group. In the sympathetic renal denervation intervention group, early recurrence was greatly decreased and the electrocardiogram (ECG) was more stable and regular. Myocardial histology showed decreased cellular damage and fibrosis in the sympathetic renal denervation group. Sympathetic renal denervation intervention significantly reduced sympathetic nerve activity, according to neurotransmitter measures. Electrophysiological indications of early recurrence following defibrillation in post-MI ventricular fibrillation are linked to sympathetic renal denervation's therapeutic benefits. Myocardial damage and fibrosis may be reduced, ECG features improved, and the early recurrence rate reduced by sympathetic renal denervation. One possible method of sympathetic renal denervation intervention is reduced sympathetic nerve activity.

Novel laparoscopic renal denervation immediately reduces atrial fibrillation inducibility: a swine model study

Catheter-based approaches may have inherent limitations in achieving effective renal denervation (RDN) and treatment of atrial fibrillation (AF). This study aimed to investigate the acute effects of novel laparoscopic RDN on modulating AF inducibility using a swine model. Four and five swine were randomly allocated to the sham and RDN groups, respectively. Each swine underwent measurement of the atrial effective refractory period (AERP) and AF induction tests using burst atrial pacing before and immediately after sham or RDN procedures with and without vagal nerve stimulation (VNS). A laparoscopic RDN procedure circumferentially ablated the renal nerves round the renal arteries using radiofrequency energy. There was no significant difference in the baseline AERP between the two groups (p > 0.05). Under VNS, AERP was significantly increased by 20 ms after laparoscopic RDN (95% CI = 0–30, p = 0.004). Compared to the sham group, the RDN group showed significantly reduced AF inducibility [OR (95% CI) = 0.32 (0.13–0.76) and 0.24 (0.11–0.57) with and without VNS, respectively]. After laparoscopic RDN, the duration of inducible AF episodes was significantly shortened from 28 (10–77) s to 7 (3–11) s (p < 0.001). The novel laparoscopic RDN can immediately reduce AF inducibility in a swine model.

Abstract 15572: Assessing the Impact of Renal Denervation on Heart Failure: Results From the Pooled Analysis of Randomized Controlled Trials

Introduction: Renal denervation (RDN), first developed for hypertension management, is currently being investigated as a potential treatment for heart failure (HF). However, its efficacy and safety for these patients necessitate further investigation. Hypothesis: This study aimed to assess the impact of renal denervation on various clinical and hemodynamic parameters in heart failure patients. Methods: A comprehensive search of PubMed, Cochrane Library, and Embase databases was performed for randomized controlled trials (RCTs) comparing RDN with standard care or placebo in HF patients, published until January 2023. Data were pooled using a random-effects model, and results were reported as Mean Differences (MD) with a 95% confidence interval (CI). All statistical analyses were performed using R software (version 4.0.3) with the metafor and meta packages. Results: The search identified five RCTs involving 208 patients (103 in the RDN group and 105 in the control group). RDN was associated with significant improvements in left ventricular ejection fraction (MD: 4.48%, 95% CI: 0.57-8.4%, P=0.02, I2=77%), 6-minute walk distance (MD: 78.71 meters, 95% CI: 47.01-110.41 meters, P&lt;0.01, I2=0%), left ventricular end-systolic diameter (MD: -3.18 mm, 95% CI: -5.64 to -0.72 mm, P=0.01, I2=24%), and left ventricular end-diastolic diameter (MD: -4.16 mm, 95% CI: -6.04 to -2.29 mm, P&lt;0.01, I2=0%). However, no significant changes were noted in left atrial diameter (MD: -4.49 mm, 95% CI: -9.19 to 0.20 mm, P=0.06, I2=79%), New York Heart Association class (MD: -0.71, 95% CI: -1.65 to 0.24, P=0.14, I2=96%), heart rate (MD: -3.71 beats per minute, 95% CI: -8.45 to 1.03 beats per minute, P=0.12, I2=62%), systolic blood pressure (MD: -0.35 mmHg, 95% CI: -11.51 to 10.79 mmHg, P=0.95, I2=88%), and diastolic blood pressure (MD: -1.46 mmHg, 95% CI: -7.12 to 4.19 mmHg, P=0.61, I2=79%). Conclusions: RDN has shown the potential to improve left ventricular function and exercise capacity in managing heart failure. The results, marked by high heterogeneity in some outcomes and constrained by the limited number of trials and patients, necessitate larger multicenter trials for validation and further exploration of renal denervation's role in heart failure management.

Abstract 18210: Renal Denervation in Management of Heart Failure: A Systematic Review and Meta-Analysis

Introduction: Renal denervation (RDN) is a novel intervention targeting sympathetic nerves along the renal artery. Ablation of this neurohormonal pathway alters the pathophysiology of heart failure (HF) and can lead to improvements in clinical outcomes. We conducted a systematic review and meta-analysis to review the outcome of heart failure patients undergoing RDN. Methods: We performed a comprehensive search on PubMed, Cochrane, and Embase from inceptions through June 2023 using the string “(“renal denervation” OR “renal sympathetic denervation “) AND (“heart failure” OR “congestive heart failure”)”. Exclusion criteria include non-human trials, studies without a baseline and control, and studies without outcomes of interest. We collected the number of patients with HF and the resulting outcomes. Outcomes of interest include left ventricular ejection fraction (LVEF), six minute walk distance (SMWD), NT- proBNP, and systolic and diastolic pressures. The random-effects model was used to calculate the odds ratios (OR), mean differences (MD), and confidence intervals (CI). A p value &lt;0.05 was considered statistically significant. Heterogeneity was assessed using the Higgins I2 index. Results: Nine randomized control trials involving a total of 513 patients were included in our analysis. We found a significant difference when comparing the RDN group to the control groups for LVEF (MD 1.39, 95% CI [0.03,2.75]), SMWD (MD 200.13 m, 95% CI [187.32,212.95]), NT-proBNP (MD -397.16 pg/ml, 95% CI [-438.90, -355.42]), SBP (MD -3.69 mmHg, 95% CI [-7.24, -0.14]) within 12 months. Interestingly, difference in DBP was insignificant (MD -1.13 mmHg, 95% CI [-3.33,1.07]). Our RDN group had a significant decrease in hospital admissions (OR 0.83, 95% CI [0.25,2.77]) for HF exacerbation within 12 month following denervation. When comparing RND to baseline, we found a significant difference in LVEF (MD 1.90, 95% CI [0.64,3.16]) and SMWD (MD 106.56 m, 95% CI [88.72,124.40]). Conclusions: Our analysis demonstrates RDN results in a significant difference in LVEF, SMWD, NT-proBNP, and SBP in patients with HF when compared to control and baseline. However, further research is needed with larger samples to establish the safety and effectiveness of RDN as a viable therapy in HF.

Laparoscopic approach for renal denervation: an experimental study on animals

Aim. To study the efficacy and safety of laparoscopic mechanical renal denervation.Methods. Thirty sheep with mean weight 92.3±2.1 kg were divided in 2 groups: control group (group I, n=15) and mechanical laparoscopic renal denervation group (group II, n=15). The follow-up period was 6 months. The following parameters were assessed: blood pressure in response to high-frequency electrical intraluminal stimulation, creatinine, blood urea nitrogen test (BUN), damage to the renal arteries according to the result of angiography, the degree of destruction of nerve fibers according to histological examination.Results. All animals were alive during the entire observation period. The creatinine and BUN were within the normal ranges during the observation period. Angiography of the renal arteries did not reveal iatrogenic stenotic lesions. After 6 months in group 2 there was hypertensive response of blood pressure to high-frequency electrical stimulation (in-creased systolic blood pressure ∆70.27±5.31 (p&gt;0.005), diastolic blood pressure ∆49.87±6.05 (p&gt;0.005)). After 6 months, the animals were euthonised, further histological examination was completed. Histological examination: in the group II, there was swelling and vacuolization of the nerve fiber without signs of demyelination.Conclusions. Laparoscopic mechanical renal denervation is a safe technique. However, the hypotensive effect is short-term.

Late outcomes of renal denervation are more favourable than early ones: facts or fancies?

Following second-generation randomized trials, there is evidence that renal denervation (RDN) decreases blood pressure (BP), although to a lesser extent than suggested in the initial controlled and observational studies. The recent publication of the 36-month follow-up of the Symplicity HTN-3 trial has raised expectations, suggesting increasing, late benefits of the procedure, despite initially negative results. These findings come after those obtained at 36months in the sham-controlled trial SPYRAL HTN-ON MED and in the Global Symplicity Registry. However, they are susceptible to biases inherent in observational studies (after unblinding for sham-control) and non-random, substantial attrition of treatment groups at 36 months, and used interpolation of missing BPs. More importantly, in SPYRAL HTN-ON MED and Symplicity HTN-3, long-term BP changes in patients from the initial RDN group were compared with those in a heterogeneous control group, including both control patients who did not benefit from RDN and patients who eventually crossed over to RDN. In crossover patients, the last BP before RDN was imputed to subsequent follow-up. In Symplicity HTN-3, this particular approach led to the claim of increasing long-term benefits of RDN. However, comparison of BP changes in patients from the RDN group and control patients who did not undergo RDN, without imputation of BPs from crossover patients, does not support this view. The good news is that despite the suggestion of sympathetic nerve regrowth after RDN in some animal models, there is no strong signal in favour of a decreasing effect of RDN over time, up to 24 or even 36months. Still, current data do not support a long-term increase in the effect of RDN and the durability of RDN-related BP reduction remains to be formally demonstrated.

Denervation aggravates renal ischemia reperfusion injury via BMAL1-mediated Nrf2/ARE pathway

AimTo explore the change of clock gene rhythm under renal denervation (RDN) and its effect on renal function and oxidative stress during renal ischemia-reperfusion (IR) injury. MethodC57/BL6 mice were randomly divided into 4 groups at daytime 7 A M (zeitgeber time [ZT] 0) or at nighttime 7 P M (ZT12) in respectively: Sham (S) group, RDN group, IR group and RDN + IR (DIR) group. Renal pathological and functional changes were assessed by H&E staining, and serum creatinine, urea nitrogen and neutrophil gelatinase-associated lipocalin levels. Renal oxidative stress was detected by SOD and MDA levels, and renal inflammation was measured by IL-6, IL-17 A F and TNF-ɑ levels. BMAL1, CLOCK, Nrf2 and HO-1 mRNA and protein expressions were tested by qPCR and Western Blot. ResultCompared with S groups, the rhythm of BMAL1, CLOCK and Nrf2 genes in the kidney were disordered in RDN groups, while renal pathological and functional indexes did not change significantly. Compared with IR groups, renal pathological and functional indexes were significantly higher in the DIR groups, as well as oxidative stress and inflammation in renal tissues. The nocturnal IR injury in the RDN kidney was the worst while the BMAL1, Nrf2 and HO-1 expressions were the highest. In DIR groups, renal injury was aggravated after the Brusatol treatment, but there was no significant improvement after the t-BHQ treatment at night, which might be consistent with the changes of Nrf2 and HO-1 protein expressions. ConclusionRDN lead to the disruption of BMAL1-mediated Nrf2 rhythm accumulation in the kidney, which reduced the renal ability to resist oxidative stress and inflammation, due to the impaired effect of activating Nrf2/ARE pathway in renal IR injury at nighttime.

Effect of renal denervation on cardiac remodelling and function in rats with chronic intermittent hypoxia.

Chronic intermittent hypoxia (CIH) mimicking obstructive sleep apnea elicits divergent outcomes in the cardiovascular systems. The effect of renal denervation (RDN) on the heart during CIH remains unclear. We aimed to explore the effect of RDN on cardiac remodelling in rats exposed to CIH and to discuss the underlying mechanisms. Adult Sprague Dawley rats were divided into four groups: control, control+RDN, CIH (CIH exposure for 6 weeks, nadir of 5%-7% to peak of 21% O2, 20 cycles/h, 8 h/day) and CIH+ RDN group. Echocardiography, cardiac fibrosis, left ventricle (LV) expressions of nuclear factor-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway and inflammatory factors were tested at the end of the study. Cardiac structural remodelling and dysfunction were induced by CIH and attenuated by RDN. Myocardial fibrosis was more severe in the CIH group than in the control group and improved in the CIH + RDN group. Sympathetic activity reflected by tyrosine hydroxylase (TH) expression and noradrenaline were significantly elevated after CIH but blunted by RDN. CIH downregulated LV protein expressions of Nrf2 and HO-1, which was activated by RDN. The downstream of Nrf2/HO-1, such as NQO1 and SOD expression, elevated following RDN. RDN also decreased the mRNA expression of IL-1β and IL-6. Notably, control+RDN did not affect cardiac remodelling and Nrf2/HO-1 compared with the control. Taken together, we found that RDN exerted cardio-protective effects in a rat model of CIH involving Nrf2/HO-1 pathway and inflammation.