120 Safety and efficacy of renal artery denervation for uncontrolled-resistant hypertension in a high risk population with CKD: the Verona real-world experience

Aims To evaluate the safety and the efficacy of catheter-based radiofrequency renal sympathetic denervation (RSD) in a daily practice population of patients with uncontrolled resistant hypertension on top of medical therapy. Methods and results Consecutive unselected patients with uncontrolled resistant hypertension undergoing RSD were enrolled. Office and ambulatory blood pressure (BP) monitoring were collected at baseline and 3, 6, and 12 months after RSD. Efficacy was assessed also in patients with an estimated glomerular filtration rate below 45 ml/min/1.73 m2. Patients were defined responders to RSD if systolic BP decreased by at least 5 mmHg at ambulatory BP or by 10 mmHg at office BP at the last follow-up available. Fifty-four patients with multiple comorbidities underwent RSD for uncontrolled-resistant hypertension from 2012 to 2021. Baseline office and ambulatory BP was 161.0/87.2 ± 24.1/15.6 mmHg and 155.4/87.5 ± 19.3/14.6 mmHg, respectively. At 12-month follow-up a significant reduction of office and ambulatory systolic BP, respectively by − 15.66 ± 29.73 mmHg (P < 0.01) and by − 11.3 ± 23.1 mmHg (P < 0.05), was noticed. BP reduction at 12-month follow-up among patients with eGFR <45 ml/min was similar to that obtained in patients with higher eGFR. Among patients treated before July 2020 with available follow-up (45/54) 36 patients (80%) were classified as responders. Combined hypertension, higher ambulatory systolic BP and lower E/E’ at baseline emerged as predictors of success of RSD at univariate analysis. Among responders and non-responders, the average medication number showed no significant difference at baseline and during follow-up. No major complications were observed and renal function was stable up to 12 months, even in patients with lowest eGFR at baseline. Conclusions RSD is safe and feasible in patients with uncontrolled resistant hypertension on top of medical therapy, even in a high-risk CKD population with multiple comorbidities, with a significant reduction of systolic BP and a trend of reduction of the diastolic BP up to 12 months. 775 Figure

sST2 Predicts Short Term Therapy Success in Patients with Therapy Resistant Hypertension after Renal Sympathetic Denervation

Background: Renal sympathetic denervation (RSD) has provided promising data in its ability to treat therapy resistant arterial hypertension. The effect of RSD on sST-2, a promising biomarker for risk stratification in cardiovascular diseases, has so far not been systematically studied. Methods: We evaluated serum levels of sST-2 and clinical parameter including left ventricular mass (LVM) in 54 patients with resistant hypertension (RH) undergoing bilateral RSD at baseline as well as at one and/or three months. Results: After RSD, mean office blood pressure showed a significant decrease after one month (p < 0.001). On echocardiography a reduction of LVM was observed at three months (p < 0.01). This was accompanied by a significant decrease of sST-2 levels at three months (sST-2 baseline: 6310.1 ± 3246.0 pg/mL vs. sST-2 three months: 4703.8 ± 1585.9 pg/mL, p = 0.048). Furthermore, baseline sST-2 levels were positively correlated with systolic blood pressure at one month (r = 0.514, p < 0.01) but not three months, indicating a potential predictive value of sST-2 for early intervention success. Conclusion: In patients with RH, RSD is associated with a significant decrease of sST-2 levels after three months, indicating sST-2 to be involved in remodeling processes after RSD. Furthermore, lower sST-2 levels at baseline might be a potential predictor of early intervention success of RSD.

Systematic review of renal denervation for the management of cardiac arrhythmias

Background In the wake of the controversy surrounding the SYMPLICITY HTN-3 trial and data from subsequent trials, this review aims to perform an updated and more comprehensive review of the impact of renal sympathetic denervation on cardiac arrhythmias. Methods and results A systematic search was performed using the Medline, Scopus and Embase databases using the terms “Renal Denervation” AND “Arrhythmias or Atrial or Ventricular”, limited to Human and English language studies within the last 10 years. This search yielded 19 relevant studies (n = 6 randomised controlled trials, n = 13 non-randomised cohort studies) which comprised 783 patients. The studies show RSD is a safe procedure, not associated with increases in complications or mortality post-procedure. Importantly, there is no evidence RSD is associated with a deterioration in renal function, even in patients with chronic kidney disease. RSD with or without adjunctive pulmonary vein isolation (PVI) is associated with improvements in freedom from atrial fibrillation (AF), premature atrial complexes (PACs), ventricular arrhythmias and other echocardiographic parameters. Significant reductions in ambulatory and office blood pressure were also observed in the majority of studies. Conclusion This review provides evidence based on original research that ‘second generation’ RSD is safe and is associated with reductions in short-term blood pressure and AF burden. However, the authors cannot draw firm conclusions with regards to less prominent arrhythmia subtypes due to the paucity of evidence available. Large multi-centre RCTs investigating the role of RSD are necessary to comprehensively assess the efficacy of the procedure treating various arrhythmias. Graphic abstract

Comparison of Long‐Term Outcomes for Responders Versus Non‐Responders Following Renal Denervation in Resistant Hypertension

Background Recent trial results support the efficacy of renal sympathetic denervation in lowering blood pressure (BP). While BP reduction in general is associated with a clinically meaningful reduction in cardiovascular events and mortality, such a relationship has not been described for patients undergoing renal sympathetic denervation. Methods and Results Clinical events were assessed in patients who underwent renal sympathetic denervation at our center using telephone‐ and clinical follow‐up, interviews with general practitioners, as well as review of hospital databases. Event rates were compared between BP responders (≥5 mm Hg 24‐hour ambulatory BP reduction) and non‐responders; 296 patients were included. Compared with baseline, 24‐hour systolic ambulatory BP was reduced by 8.3±12.2 mm Hg and diastolic BP by 4.8±7.0 mm Hg ( P <0.001 for both) after 3 months. One hundred eighty patients were classified as BP responders and 116 as non‐responders. During a median follow‐up time of 48 months, significantly less major adverse cardiovascular events (cardiovascular death, stroke, myocardial infarction, critical limb ischemia, renal failure) occurred in responders than in non‐responders (22 versus 23 events, hazard ratio [HR], 0.53 [95% CI, 0.28 to 0.97], P =0.041). This was consistent after adjustment for potential confounders as well as confirmed by propensity‐score matching. A proportional relationship was found between BP reduction after 3 months and frequency of major adverse cardiovascular events (HR, 0.75 [95% CI, 0.58 to 0.97] per 10 mm Hg 24‐hour systolic ambulatory BP reduction). Conclusions Based on these observational data, blood pressure response to renal sympathetic denervation is associated with improved long‐term clinical outcome.

Optimal Strategy for HIFU-Based Renal Sympathetic Denervation in Canines

Background: The association between the treatment efficacy and safety of high-intensity focused ultrasound (HIFU)-based renal sympathetic denervation (RDN) and the acoustic energy dose applied has not been fully studied and may provide important understanding of the mechanism that led to failure of the WAVE IV trial. The objective of this study was to externally deliver different HIFU doses to canines for RDN treatment and to investigate the optimal energy dose for HIFU-based RDN.Methods: Thirty canines were divided into five RDN groups according to dose of acoustic energy applied, and a sham control group that consisted of four canines was used for comparisons. All animals in the RDN groups underwent the RDN procedure with different acoustic energy doses, while in the sham control group, renal arteries were harvested without being subjected to acoustic energy delivery and were imaged using color Doppler flow imaging (CDFI). Blood pressure (BP) was recorded, and blood samples were collected before the RDN procedure and at 28 days after the RDN procedure. Histological examinations and measurement of renal tissue norepinephrine concentration were performed in all retrieved samples.Results: Suppression of BP was significant in the 300 W (15.17/8.33 ± 1.47/1.21 mmHg), 250 W (14.67/9.33 ± 1.21/1.37 mmHg), and 200 W (13.17/9.17 ± 2.32/1.84 mmHg) groups. Semiquantitative histological assessment of periarterial nerves around the kidney revealed that target nerves in the 300 W (9.77 ± 0.63), 250 W (9.42 ± 0.67), and 200 W (9.58 ± 0.54) groups had the highest nerve injury scores, followed by the 150 W group (5.29 ± 0.62). Furthermore, decreased renal tissue norepinephrine concentration, together with decreased expression of tyrosine hydroxylase in the 300, 250, and 200 W groups demonstrated effective sympathetic depression following sufficient acoustic energy deposition. However, the renal artery injury score in the 300 W group (0.93 ± 0.13) was significantly higher than in the other groups (p &lt; 0.001).Conclusion: This study provides evidence that RDN effectiveness is based on the energy dose delivered and that 200–250 W is effective and safe in normal-sized canines.

Endovascular renal sympathetic denervation to improve heart failure with reduced ejection fraction: the IMPROVE-HF-I study

Introduction The aim of the present study was to assess the safety and efficacy of renal sympathetic denervation (RDN) in patients with heart failure with reduced ejection fraction (HFrEF). Methods We randomly assigned 50 patients with a left ventricular ejection fraction (LVEF) ≤ 35% and NYHA class ≥ II, in a 1:1 ratio, to either RDN and optimal medical therapy (OMT) or OMT alone. The primary safety endpoint was the occurrence of a combined endpoint of cardiovascular death, rehospitalisation for heart failure, and acute kidney injury at 6 months. The primary efficacy endpoint was the change in iodine-123 meta-iodobenzylguanidine (123I‑MIBG) heart-to-mediastinum ratio (HMR) at 6 months. Results Mean age was 60 ± 9 years, 86% was male and mean LVEF was 33 ± 8%. At 6 months, the primary safety endpoint occurred in 8.3% vs 8.0% in the RDN and OMT groups, respectively (p = 0.97). At 6 months, the mean change in late HMR was −0.02 (95% CI: −0.08 to 0.12) in the RDN group, versus −0.02 (95% CI: −0.09 to 0.12) in the OMT group (p = 0.95) whereas the mean change in washout rate was 2.34 (95% CI: −6.35 to 1.67) in the RDN group versus −2.59 (95% CI: −1.61 to 6.79) in the OMT group (p-value 0.09). Conclusion RDN with the Vessix system in patients with HFrEF was safe, but did not result in significant changes in cardiac sympathetic nerve activity at 6 months as measured using 123I‑MIBG.

Renal sympathetic denervation in patients with resistant hypertension. Results of long-term prospective follow-up

Objective. Renal sympathetic denervation (RDN) is one of the invasive treatment options for the patients with hypertension (HTN) who are resistant to antihypertensive therapy (AHT). The short-term efficacy of RDN has been proven in a number of randomized clinical trials, but remains controversial, the data on its long-term efficacy are limited. The aim of our study was to evaluate the natural course of HTN, to assess long-term major adverse cardiovascular events (MACE) and other outcomes, as well as AHT efficacy and its features in patients with resistant HTN after bilateral RDN during extended prospective follow-up. Design and methods. We included 22 patients with truly resistant HTN (median 57 y. o., 9 males), in whom RDN was performed during 2012–2015 in the clinical center of excellence. We assessed initial and further (after 1 year and after ≥ 5 years) clinical, laboratory and anthropometric parameters, as well as detailed AHT history. Long-term MACE and other clinically significant outcomes were recorded. At baseline and follow-up, the quality of life (QoL) was determined with the use of EQ-5D questionnaire at all time points. Multiple linear regression was used to find possible predictors of the efficacy of RDN. Results. A significant and sustained drop in office and ambulatory systolic blood pressure (SBP) and diastolic blood pressure (DBP) was observed at 12 months after RDN compared to baseline values (∆ –24 and –12 mm Hg, p < 0,005; ∆ –10 and –7 mm Hg, p < 0,05, respectively). There were 7 patients with office SBP on-target, and 12 patients were considered responders (∆ SBP > 10 mm Hg). These numbers increased to 10 and 14 patients after ≥ 5 years after RDN. A causal relationship between changes in office SBP was found only for the baseline SBP (β -0,6, p = 0,02). No differences in the number of medications were noted during follow-up (4,4; 4,1 and 4,1 drugs, p = 0,41). During the follow-up 10 MACE occurred and 5 patients were diagnosed with various types of cancer; there were no fatal outcomes. The QoL significantly improved a year after RDN (+9,7 points, p = 0,01), however, a negative trend was observed in the next 5 years with return to reference level. No association was observed between BP and QoL changes at two timepoints. Conclusions. The RDN shows a pronounced clinical effect in patients with resistant HTN up to 5 years, and is not accompanied by an AHT intensification, but is not associated with QoL changes. The initial positive trend for QoL completely harked back after 5 years which may be associated with the development of MACE. The only predictor of RDN positive effect is baseline SBP level.