Baseline Office Systolic Blood Pressure Research Articles

Effects of Oral Butyrate on Blood Pressure in Patients With Hypertension: A Randomized, Placebo-Controlled Trial.

The microbiota-derived short chain fatty acid butyrate has been shown to lower blood pressure (BP) in rodent studies. Nonetheless, the net effect of butyrate on hypertension in humans remains uncovered. In this study, for the first time, we aimed to determine the effect of oral butyrate on BP in patients with hypertension. We performed a double-blind randomized placebo-controlled trial including 23 patients with hypertension. Antihypertensive medication was discontinued for the duration of the study with a washout period of 4 weeks before starting the intervention. Participants received daily oral capsules containing either sodium butyrate or placebo with an equivalent dosage of sodium chloride for 4 weeks. The primary outcome was daytime 24-hour systolic BP. Differences between groups over time were assessed using linear mixed models (group-by-time interaction). Study participants (59.0±3.7 years; 56.5% female) had an average baseline office systolic BP of 143.5±14.6 mm Hg and diastolic BP of 93.0±8.3 mm Hg. Daytime 24-hour systolic and diastolic BP significantly increased over the intervention period in the butyrate compared with the placebo group, with an increase of +9.63 (95% CI, 2.02-17.20) mm Hg in daytime 24-hour systolic BP and +5.08 (95% CI, 1.34-8.78) mm Hg in diastolic BP over 4 weeks. Butyrate levels significantly increased in plasma, but not in feces, upon butyrate intake, underscoring its absorption. Four-week treatment with oral butyrate increased daytime systolic and diastolic BP in subjects with hypertension. Our findings implicate that butyrate does not have beneficial effects on human hypertension, which warrants caution in future butyrate intervention studies. URL: https://onderzoekmetmensen.nl/; Unique identifier: NL8924.

HIGHER BASELINE SYSTOLIC BLOOD PRESSURE IS ASSOCIATED WITH GREATER BLOOD PRESSURE REDUCTIONS FOLLOWING RADIOFREQUENCY RENAL DENERVATION IN A POOLED COHORT OF OVER 3900 PATIENTS

Objective: Uncontrolled hypertension (HTN) is the leading global risk factor for cardiovascular disease, and higher systolic blood pressure (SBP) increases this risk. Radiofrequency renal denervation (RF RDN) has been shown to reduce BP effectively in patients with uncontrolled HTN. We investigated the relationship between increasing baseline SBP and its change after RF RDN. Design and method: Patients undergoing RF RDN (N=3974) were pooled from global clinical trials in patients on antihypertensive drugs: SPYRAL First-In-Man, SYMPLICITY HTN-3, HTN-Japan, SPYRAL HTN ON-MED, and the Global SYMPLICITY Registry DEFINE. Office and 24-h ambulatory SBP at baseline and 6 months after RF RDN were evaluated. Linear regression analysis was performed to evaluate the correlation between baseline and SBP change after 6 months (SBP change=intercept+slope∗baseline SBP). Results: The baseline SBP for office and 24-h ambulatory BP were 167±24mmHg and 154±18mmHg, respectively. Patients were prescribed 4.4±1.5 antihypertensive drugs at baseline. After 6 months, prescribed antihypertensive drugs decreased to 4.3±1.5 (p<0.0001). In both office and 24-h ambulatory SBP, baseline SBP correlation with SBP change after 6 months was statistically significant; every 1mmHg increase in baseline office SBP was associated with a 0.59mmHg (r2=0.30; p<0.001) reduction in SBP, and every 1mmHg increase in baseline 24-h ambulatory SBP was associated with a 0.45mmHg (r2=0.19; p<0.001) reduction in SBP at 6 months. According to this linear regression, a baseline office SBP of 160mmHg, 170mmHg and 180mmHg were associated with 6 months office SBP reduction by -9.2mmHg, -15.1mmHg and -21.0mmHg, respectively (Figure). Reductions in SBP of this magnitude have previously been shown to correspond with substantial reductions in the risk of cardiovascular events. Conclusions: A continuous and inverse relationship was observed between baseline SBP and 6 months SBP change in patients with uncontrolled HTN undergoing RF RDN. Higher baseline SBP led to a greater reduction in SBP and may derive greater benefit from an RDN procedure. These findings may help clinicians and patients in their shared decision making regarding their BP management. However, this is a retrospective analysis which needs further prospective validation.

A novel, proof-of-concept radiofrequency renal denervation strategy to improve procedural efficiency: 12-month results from the SPYRAL DYSTAL pilot study

BackgroundCatheter-based renal sympathetic denervation (RDN) reduced blood pressure (BP) in multiple randomized sham-controlled trials of patients with uncontrolled hypertension (HTN). We tested proof-of-concept for a more selective treatment strategy, exclusively targeting these areas to improve the efficiency of the procedure. MethodsThe SPYRAL DYSTAL Pilot study was designed to mirror the SPYRAL HTN-OFF MED Pivotal study, enabling comparison with a propensity score adjusted active-control group. Patients were antihypertensive medication-free for one month before undergoing BP assessment. Those with office BP of 150–180/>90 mmHg and with an ambulatory systolic BP of 140–170 mmHg were selected to undergo open label treatment, delivering energy only to the distal main renal arteries and first order branches. Patients from DYSTAL were compared with patients who underwent maximized RF RDN treatment in the prior randomized OFF MED trial at 3 months. After 3 months, patients resumed antihypertensive medications as indicated. Safety and efficacy outcomes were assessed post hoc through 12 months. ResultsThe SPYRAL DYSTAL Pilot study treated 56 HTN patients. Baseline office systolic BP (OSBP) and 24-h ambulatory systolic BP (ASBP) were similar between DYSTAL and OFF MED patient groups. The number of ablations (32.3 ± 8.0 vs 46.6 ± 15.3, p < 0.001), procedure time (67 ± 21 min vs 99 ± 36 min; p < 0.001), and contrast volume (173 ± 77 cc vs 208 ± 96 cc; p = 0.014) were significantly lower with the simplified treatment strategy. OSBP and ASBP changes compared with baseline were −9.0 and −1.4 mmHg at 3 months, −20.3 and −13.9 mmHg at 6 months, and −20.3 and −16.6 mmHg at 12 months, respectively. During the medication up-titration phase, BP reductions among DYSTAL patients were similar to reductions observed in OFF MED through 12 months, with comparable number of drugs (1.4 and 1.5 medications, respectively (P=NS)). Two adverse events related to guidewire placement were reported. ConclusionIn this pilot study, focusing ablation treatment on the distal main and proximal branch renal arteries was performed, resulting in fewer RF lesions, and reduced contrast volume and procedure time. Whether BP reductions are similar between a selective vs. maximized RDN approach requires further prospective study.

Association between baseline office blood pressure level and the incidence and development of long-term frailty in the community-dwelling very elderly with hypertension.

Frailty is the most important risk factor causing disability in the elderly. Hypertension is one of the most common chronic diseases in the elderly and is closely related to frailty, but there is still controversy about the association between blood pressure and frailty. To explore the association between baseline blood pressure level and the incident and development of long-term frailty in the community-dwelling very elderly (i.e., over 80 years old [1]) with hypertension, in order to provide a basis for scientific blood pressure management of very elderly hypertension. In this study, very elderly hypertensive patients who received comprehensive geriatric assessment from January to June 2019 and with complete data were included, and follow-up was conducted from January 1 to February 14, 2023. A total of 330 very elderly individuals with hypertension were enrolled in this study. FRAIL scale was used to evaluate frailty. Binomial logistic regression analysis was used to calculate the OR and 95%CI between baseline systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP) levels and long-term incident and development of frailty. The dose-response relationship between baseline office SBP, DBP or PP levels and incident frailty and its development was analyzed by Generalized Additive Model (GAM) using smooth curve fitting and threshold effect analysis. Smooth curve fitting and threshold effect analysis showed that the relationship between baseline office SBP level and incident frailty was U-shaped, with the nadir of the U-shaped curve at 135 mmHg after adjustment. Baseline office SBP, PP level and development frailty was U-shaped and the nadir was 140 mmHg and 77 mmHg. In the community-dwelling very elderly with hypertension, baseline office SBP level had a relationship with long-term incident frailty and its development and PP level had a relationship with long-term development of frailty.

Abstract 13852: Sex Differences in Blood Pressure Reduction and Cardiovascular Outcomes in Patients With Resistant Hypertension Undergoing Radiofrequency Renal Denervation: Global SYMPLICITY Registry DEFINE

Introduction: Hypertension (HTN) prevalence and outcomes differ by sex. Radiofrequency renal denervation (RF RDN) safely reduces blood pressure (BP) in patients with resistant HTN. Hypothesis: After RF RDN, there are no sex-based differences in BP changes and cardiovascular (CV) outcomes. Methods: The Global SYMPLICITY Registry (GSR) DEFINE is an all-comer registry of patients with uncontrolled BP undergoing RF RDN. BP changes (analysis of covariance [ANCOVA] adjusted for baseline BP and age), CV death, stroke, myocardial infarction (MI) rates at 3yrs were compared between sexes with office systolic BP (OSBP) ≥140mmHg, prescribed ≥3 anti-HTN drugs. Results: Patients enrolled up to March 2023 were included (N=2502, female=1062). Females were older (62 vs 59 y; p&lt;0.0001), less likely to have a history of sleep apnea (12.5 vs 25.0% p&lt;0.0001), cardiac disease (45.2 vs 50.3%; p&lt;0.0012) and smoking (19.1 vs 41.3%; p&lt;0.0001). Body mass index, rates of diabetes and chronic kidney disease, number of anti-HTN drugs (5.1±1.5 in both sexes; p=0.88) and 24-hr SBP were similar by sex. Baseline OSBP was higher in females (174±23 vs 169±19mmHg; p&lt;0.0001). After 3yrs, OSBP significantly decreased in both sexes from baseline (female: -21.5mmHg vs male: -20.4mmHg; ANCOVA adjusted difference: 3.2mmHg [95% CI: 0.5 to 6.0; p=0.021]). There was no difference in 24-hr SBP change (Figure 1A) or number of anti-HTN drugs by sex. CV death rate was significantly higher in females (4.1% vs 2.1% vs p=0.024), but MI rate was significantly lower in females (1.3% vs 3.5%; p=0.007). Stroke rate was similar by sex (Figure 1). Conclusion: Females with resistant hypertension referred for RF RDN were older, had higher OSBP with fewer comorbidities compared to males. Despite similar BP reductions up to 3yrs after RF RDN, CV death rate in females was greater than males. These results suggest the need for sex specific analyses and control of HTN in females.

ORAL SODIUM BUTYRATE INCREASES DAYTIME SYSTOLIC BLOOD PRESSURE IN HYPERTENSIVE PATIENTS: A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED TRIAL

Objective: The microbiota-derived short chain fatty acid (SCFA) butyrate has been shown to modulate blood pressure (BP) in rodent studies, while in humans, plasma butyrate levels have been associated with BP. Nonetheless the net effect of butyrate on hypertension in humans remains uncovered. In this study, we aimed to determine the effect of oral butyrate on BP in hypertensive patients. Design and method: We performed a double-blind randomized placebo-controlled trial including 23 patients with grade I hypertension. Antihypertensive medication was discontinued for the duration of the study with a wash-out period of four weeks before starting the intervention. Participants received either oral sodium butyrate capsules 4 g per day or placebo capsules with an equivalent amount of sodium chloride for four weeks. The primary outcome was daytime 24-hours systolic BP. We also collected data on short-term heart rate variability (HRV) using finger photoplethysmography, and extracellular water percentage using body impedance analyses. We measured plasma renin, aldosterone, and fecal SCFA levels. Gut microbiota composition was determined using 16S rRNA sequencing. Differences between groups over time were assessed using linear mixed models (group*time interaction). Results: Study participants had a mean age of 59.0 ± 3.7 years, 56.5% female and an average baseline office systolic BP of 143.5 ± 14.6 mmHg and diastolic BP of 93.0 ± 8.3 mmHg. Daytime 24-hours systolic and diastolic BP significantly increased over the intervention period in the butyrate compared to the -placebo group, with an effect size of 9.65 (95%CI 3.88 - 17.15) mmHg in daytime 24-hours systolic BP and 5.08 (95%CI 1.89 - 8.76) mmHg in diastolic BP in the linear mixed model. Heart rate and extracellular water percentage changes were not significantly different between the groups. There was a trend towards increasing HRV in the butyrate group (group*time p = 0.078), but no significant changes in renin and aldosterone levels, nor in fecal SCFA levels. Butyrate did not impact gut microbiota composition substantially. Conclusions: Four weeks of oral butyrate treatment increased daytime systolic and diastolic BP in hypertensive subjects. Our findings implicate that not all SCFA have beneficial effects on human cardiovascular health which warrants caution in future prebiotic and butyrate intervention studies.

Blood pressure reduction in higher cardiovascular risk patients in the Global SYMPLICITY Registry

Abstract Background/Introduction The Global SYMPLICITY Registry (GSR) was designed to evaluate the safety and efficacy of renal denervation (RDN) in real-world patients. Inclusion and exclusion criteria are limited to allow assessment of the effects of RDN on patients with a wide range of comorbidities. The current analysis examines blood pressure (BP) reduction after RDN in higher cardiovascular risk patients. Purpose To evaluate blood pressure reduction after RDN in higher cardiovascular risk patients in GSR. Methods GSR is a prospective all-comers registry to evaluate the safety and efficacy of RDN. Patients are enrolled in GSR and receive radiofrequency RDN using the Symplicity Flex or Symplicity Spyral catheter. Office and ambulatory BP are measured at each follow-up (3, 6, 12, 24, and 36 months). In this post-hoc analysis, changes from baseline in office and 24-hour ambulatory systolic blood pressure were assessed in patients at higher cardiovascular risk. Higher risk was defined using baseline office systolic or diastolic BP as well as additional risk factors (Figure 1). Results As of March 2021, there were 2621 patients characterized as higher cardiovascular risk in GSR. Baseline characteristics included mean age 60.7±12.1 years, 57.6% male, 37.9% type 2 diabetes, 35.8% hypocholesterolemia, 19.7% eGFR &amp;lt;60 mL/min/1.73 m2, 16.2% left ventricular hypertrophy, 10.2% previous stroke and 9.3% previous myocardial infarction. Baseline office systolic BP (OSBP) was 168.8±22.7 mmHg and baseline ambulatory systolic BP (ASBP) 155.3±18.6 mmHg. Mean OSBP reductions after RDN in this higher risk population ranged from −13.1 mmHg at 3 months to −17.5 mmHg at 24 months and −18.9 mmHg at 36 months, and mean ASBP reductions ranged from −7.8 mmHg at 3 months to −9.8 mmHg at 24 months and −9.3 mmHg at 36 months (Figure). Conclusions Higher risk patients in GSR had sustained office and ambulatory systolic BP reductions out to 3 years after catheter-based radiofrequency RDN. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Medtronic

Clinical event reductions in high-risk patients after renal denervation projected from the global SYMPLICITY registry.

Renal denervation has been shown to lower blood pressure in sham-controlled trials and represents a device-based treatment option for hypertension. We sought to project clinical event reductions after radiofrequency renal denervation using a novel modelling approach. The Global SYMPLICITY Registry is a global, prospective all-comer registry to evaluate safety and efficacy after renal denervation. For this analysis, change in office systolic blood pressure from baseline was calculated from reported follow-up in the Global SYMPLICITY Registry. Relative risks for death and other cardiovascular events as well as numbers needed to treat for event avoidance were obtained for the respective blood pressure reductions based on previously reported meta-regression analyses for the full cohort and high-risk subgroups including type 2 diabetes, chronic kidney disease, resistant hypertension, and high basal cardiovascular risk. Average baseline office systolic blood pressure and reduction estimates for the full cohort (N=2651) were 166±25 and -14.8±0.4mmHg, respectively. Mean reductions in blood pressure ranged from -11.0--21.8mmHg for the studied high-risk subgroups. Projected relative risks ranged from 0.57 for stroke in the resistant hypertension cohort to 0.92 for death in the diabetes cohort. Significant absolute reductions in major adverse cardiovascular events over 3 years compared with the projected control (8.6 ± 0.7% observed vs. 11.7 ± 0.9% for projected control; P<0.01) were primarily due to reduced stroke incidence. The robustness of findings was confirmed in sensitivity and scenario analyses. Model-based projections suggest radiofrequency renal denervation for patients with uncontrolled hypertension adds considerable clinical benefit across a spectrum of different cohort characteristics.

CLINICAL EVENT REDUCTIONS IN HIGH-RISK HYPERTENSION PATIENTS TREATED WITH RENAL DENERVATION: 10-YEAR PROJECTIONS BASED ON 3-YEAR FOLLOW-UP FROM THE GLOBAL SYMPLICITY REGISTRY

Objective: Clinical event rates over 3 years have been published for patients with uncontrolled hypertension treated with radiofrequency renal denervation (RDN) in the Global SYMPLICITY Registry (GSR). We estimated 10-year clinical event reductions following RDN vs. a simulated control group without RDN, for two high-risk subgroups and the full GSR cohort. Design and method: A Markov model was used to compare projected 10-year clinical events [stroke, myocardial infarction (MI), cardiovascular death (CVD), heart failure (HF), all-cause death (ACD), and a composite of major adverse cardiac events (MACE, calculated as sum of stroke, MI, and CVD)] for RDN patients vs. a hypothetical control for the high atherosclerotic vascular disease risk (ASCVD) subgroup (n = 737; 69 ± 8 years), the type-2 diabetes mellitus (T2DM) subgroup (n = 1,007; 64 ± 10 years), and for all GSR patients (n = 2,651; 61 ± 12 years). The simulated control assumed maintenance of baseline office systolic blood pressure (oSBP) over time. The model was calibrated to 3-year stroke and MI events reported in the GSR and used published meta-regression data to calculate risk reduction based on cohort-specific changes in oSBP from baseline. Relative risks (RRs), events avoided, and numbers needed to treat (NNTs) were calculated at 3 and 10 years, along with the ratio of 10- vs. 3-year projected events avoided. Results: 10-year MACE events were 35.8% vs. 48.5% (-12.7%, RR = 0.74) for RDN vs. control for all GSR patients, 37.8% vs. 52.4% (-14.6%, RR = 0.72) for the high ASCVD risk cohort, and 40.5% vs. 54.0% (-13.5%, RR = 0.75) for the T2DM cohort. Across all three cohorts, events avoided were highest for stroke and lowest for MI. 10-year NNTs for MACE were comparable between the three cohorts, estimated between 7 to 8. The ratio of model-projected MACE at 10- vs. 3-years was 5.20, 5.46, and 5.03 for the full GSR, high ASCVD risk, and T2DM cohorts, respectively. Conclusions: Model-based projections based on 3- year events observed in the GSR suggest meaningful event reductions after treatment with radiofrequency RDN at 10 years that might be up to 5-times higher than the projected events avoided at 3 years under the assumption of maintained treatment effect versus baseline.

RADIOFREQUENCY RENAL SYMPATHETIC DENERVATION WITH MULTIELECTRODE CATHETERS IN PATIENTS WITH RESISTANT HYPERTENSION: EARLY PROCEDURAL RESULTS

Objective: Renal sympathetic denervation (RD) is the most promising invasive options to treat resistant hypertension (HTN). In Russian practice radiofrequency (RF) is the only feasible option. Emergence of the new RF RD multielectrode catheter systems in Russian HTN Excellence Centers provide a way to test this method. The aim of the study was to investigate the baseline characteristics of patients with resistant HTN undergoing RF RD and to determine immediate postprocedural clinical effects. Design and method: During 2018–2019, two series of RF RD procedures were performed in patients with truly resistant HTN using balloon-type (bipolar ablation) or spiral-type (unipolar ablation) multielectorde catheters. A comparative analysis of two groups of patients was carried out according to the type of catheter used. Dynamics of office systolic blood pressure (SBP) were assessed as delta between the two timepoints: at screening and at hospital discharge. The safety assessment of RF RD was performed. We applied multiple linear regression method to determine the factors associated with the delta of office SBP after RF RD. Results: A total of 48 patients taking 4 (4;6) antihypertensive drugs were included. Radiofrequency RD was performed with a balloon-type catheter in 27 patients (mean age 56 ± 12 y.o.; 12 males) and with a spiral-type catheter in 21 patients (50 ± 14 y.o.; 8 males). The duration of RF RD was significantly longer in the spiral catheter group (110 vs 60 min, p &lt; 0.001), but twice as much RF ablations (24 vs 12, p = 0.002). None had acute kidney injury after RD (delta creatinine -0.6 micromol/L; 95% CI [-3.97; 2.78]). At discharge there was a pronounced decrease in office SBP (adjusted for baseline covariates) of -26 mm Hg (95% CI [-29; -23]). The main factors associated with the delta of office SBP were: smoking status (beta = -7.95; positive if “yes’’), baseline office SBP (beta = -0.48; positive), and blood glucose (beta = 5.28; negative). Conclusions: Radiofrequency renal denervation using multielectode catheters is characterized by pronounced and favorable short-term hemodynamic effects. We have found new potential predictors of these effects. Further research will focus on testing initial hypotheses in the long term run.

MO085: 10-Year Clinical Events Avoided in Diabetic and Chronic Kidney Disease Hypertension Patients Treated With Radiofrequency Renal Denervation: Projections Based on 3-Year Data From the Global Symplicity Registry

Abstract BACKGROUND AND AIMS Clinical event rates over 3 years have been published for patients with uncontrolled hypertension treated with radiofrequency renal denervation (RDN) in the Global SYMPLICITY Registry (GSR). We estimated 10-year clinical event reductions following RDN versus a simulated control group without RDN, for the type 2 diabetes (T2DM) and chronic kidney disease (CKD) subgroups and the full GSR cohort. METHOD A Markov model based on Framingham and other multivariate risk equations [1] was used to compare projected 10-year clinical events [stroke, myocardial infarction (MI), cardiovascular death (CVD), heart failure (HF), all-cause death (ACD) and a composite of major adverse cardiac events (MACE, calculated as sum of stroke, MI and CVD)] for RDN patients versus a hypothetical control for the T2DM subgroup (n = 1007; 64 ± 10 years), the CKD subgroup (n = 630; 65 ± 12 years), and for all GSR patients (n = 2651; 61 ± 12 years). The simulated control assumed maintenance of baseline office systolic blood pressure (oSBP) over time. The model was calibrated to 3-year stroke and MI events reported in the GSR and used published meta-regression data [2] to calculate risk reduction based on cohort-specific changes in oSBP from baseline. Relative risks (RRs), events avoided, and numbers needed to treat (NNTs) were calculated at 3 and 10 years, along with the ratio of 10- versus 3-year projected events avoided. RESULTS Ten-year MACE rates were 35.8% versus 48.5% (-12.7%, RR = 0.74) for RDN versus simulated control for all patients, 40.5% versus 54.0% (-13.5%, RR = 0.75) for the T2DM subgroup and 48.4% versus 61.3% (-12.9%, RR = 0.79) for the CKD subgroup. Across the studied subgroups, avoided stroke events contributed the most to overall event reductions. RRs of events were lowest for HF (0.53–0.61) and highest for all-cause death (0.88–0.90) across the three subgroups (Table 1). Ten-year NNTs for MACE were comparable between the three cohorts, estimated between 7 and 8. The ratio of 10- versus 3-year events avoided ranged from 4.44 to 4.87 for stroke, 3.74 to 3.96 for MI and 4.22 to 5.20 for MACE across studied cohorts. CONCLUSION Based on 10-year model projections from the GSR, RDN may lead to meaningful clinical event reductions in diabetic and chronic kidney disease patients. Ten-year events avoided can be expected to be 3 to 5 times higher than those recently reported for a 3-year horizon.

Experience of using multielectrode catheter systems to perform radiofrequency renal sympathetic denervation in patients with resistant hypertension: immediate procedural effects

Aim. To investigate the baseline characteristics of patients with resistant hypertension (HTN) undergoing radiofrequency renal sympathetic denervation (RD) and to determine immediate procedural effects.Material and methods. During 2018-2019, two series of radiofrequency RD procedures were performed in patients with true resistant HTN using balloon-type (bipolar ablation) or spiral-type (unipolar ablation) multielectorde catheters. The basic demographic, clinical and laboratory characteristics of included patients were assessed. A comparative analysis of two groups was carried out depending on the type of catheter used. Dynamics of office systolic blood pressure (SBP) were assessed as ∆ between the two following timepoints: at screening and at hospital discharge. The safety of radiofrequency RD was assessed. Multiple linear regression was used to determine the factors associated with the ∆ of office SBP after radiofrequency RD.Results. A total of 48 patients taking 4 (4;6) antihypertensive drugs were sequentially included. Radiofrequency RD was performed with a balloon-type catheter in 27 patients (mean age, 56±12 years old; 12 males) and with a spiral-type catheter in 21 patients (50±14 years old; 8 males). Radiofrequency RD was significantly longer in the spiral catheter group than in balloon one (110 versus 60 minutes, p&lt;0,001), as was the mean number of RF applications (24 versus 12, p=0,002). None of the patients had acute kidney injury after RD (creatinine ∆, -0,6 µmol/L; 95% CI [-3,97; 2,78]). A total of 4 patients had complications (3 femoral arterial pseudoaneurisms, one renal arterial dissection), all of which did not affect the average length of hospital stay (from 4 to 5 days). At discharge, there was a pronounced decrease in office SBP (adjusted for baseline characteristics) with the mean of -26 mm Hg (95% CI [-29; -23]). There were following main factors associated with the office SBP ∆: smoking status (positive), baseline office SBP (positive), and blood glucose (negative).Conclusion. Radiofrequency RD using multielectode catheters is characterized by favorable short-term hemodynamic effects. We have found novel potential predictors of these effects. Further research will focus on testing initial hypotheses in the long term.

PATIENTS WITH RESISTANT HYPERTENSION AND ATRIAL FIBRILLATION ARE THE BEST RESPONDERS FOR RENAL DENERVATION

Objective: The search for the ideal candidate for renal denervation (RDN) is one of the priority treatments of patients with resistant hypertention (RH). Our objective was to identify the predictors of the efficiency of renal denervation. Design and method: The study included 112 patients with RH. The average age of patients was 53 [19; 69] years. Twenty-four (21.4%) patients had atrial fibrillation (AF). Four (16.7%) patients had chronic AF, 8 (33.3%) patients had persistent AF, and 12 (50%) – paroxysmal AF. All patients underwent RDN. Procedure was performed by an experienced electrophysiologist at the renal arteries using specialized electrode Symplicity Flex (Medtronic): ablation power = 8 - 10 W at 55°C, 4 – 10 points for each renal artery (including brunches), 2 minutes per point. Office BP and 24-hour ambulatory BP, 24-hour ECG monitoring, arrhythmia chronocard diaries were measured before, at 6 and 12 months of follow-up. A logistic regression analysis included the following parameters: gender, age, body mass index, office and 24-hour ambulatory systolic blood pressure (SBP), diabetes mellitus and the AF presence. Results: baseline office SBP and DBP in patients with RH were 185.4 ± 29.19 and 109.96 ± 17.95 respectively. Office BP decreased by 29.8 /14.1 mmHg at 12 month after RDN (p &lt; 0.001). 24-hour ambulatory SBP decreased from 161.3 ± 25.9 mm Hg to 148.1 ± 21.3 mm Hg at 12 months after the intervention, DBP from 94.3 ± 16.4 mm Hg to 87.2 ± 15.9 mmHg (p &lt; 0,001). It was found that all patients (100%) with RH and AF were responders to renal denervation. This response is defined as a reduction of office SBP of less than 10 mmHg following RDN. Whereas 17.2% of non-AF group patients were non-responders. The number of symptomatic AF paroxysms significantly decreased from 9 [2; 11] to 2 [1; 3] one year after RDN (p = 0.001). Conclusions: Patients with RH and AF are among the best candidates for RDN. It may help to improve the selection of patients with arterial hypertension for the RDN.

Efficacy and Safety of Renal Denervation for Patients with Uncontrolled Hypertension in Taiwan: 3-Year Results From the Global SYMPLICITY Registry-Taiwan (GSR-Taiwan).

It is unclear whether renal denervation (RDN) can safely result in blood pressure (BP) reductions in Asian hypertensive patients and whether such reductions would be sustainable. The study is to assess the safety and efficacy of RDN achieved by either main renal artery ablation using the Symplicity FlexTM catheter or main plus branch renal artery ablations using the Symplicity SpyralTM catheter in Taiwanese uncontrolled hypertensive patients enrolled in the Global SYMPLICITY Registry (GSR) with 3 years of follow-up. The GSR is a prospective, open-label, and all-comer registry to evaluate the safety and effectiveness of RDN in patients with uncontrolled hypertension worldwide. Among 26 patients enrolled (mean age, 59.1 ± 13.8 years), 8 were treated with the Symplicity FlexTM catheter, and 18 were treated with the Symplicity SpyralTM catheter. Baseline office systolic BP was 168.2 ± 19.8 mmHg and diastolic BP was 89.0 ± 14.3 mmHg. Office BP reductions following RDN were sustained throughout the follow-up periods of up to 3 years in the Symplicity FlexTM group and 2 years in the Symplicity SpyralTM group. In the Symplicity FlexTM group, the office systolic BP reductions were 14.9 ± 14.7 mmHg and 29.7 ± 25.9 mmHg at 3 months and 3 years, respectively (both p < 0.05 from baseline). In the Symplicity SpyralTM group, the office systolic BP reductions were 21.2 ± 28.7 mmHg and 42.4 ± 10.7 mmHg at 3 months and 2 years, respectively (both p < 0.05 from baseline). There were no significant changes in heart rate or antihypertensive medication classes. Three protocol-defined adverse events occurred in 2 patients, including new-onset end-stage renal disease, stroke, and hospitalization for new-onset heart failure. Given the susceptibility of Asian populations to hypertension, RDN, as a safe antihypertensive procedure with long-lasting BP-lowering effects, could reliably serve as an alternative or complementary BP-lowering strategy for patients with uncontrolled hypertension in Taiwan and other Asian countries.

1199Reduction in blood pressure following renal denervation for patients with differing baseline cardiovascular risk

Abstract Background Lowering blood pressure (BP) reduces clinical events. Renal denervation (RDN) is under investigation for treatment of uncontrolled hypertension and might represent a particularly attractive option for patients with high cardiovascular (CV) risk. To evaluate this proposal, it is important to determine whether baseline CV risk impacts the efficacy of RDN in lowering BP. Purpose We evaluated whether BP changes after RDN were dependent on baseline CV risk. Methods AHA/ACC Atherosclerosis CV Disease (ASCVD) risk score was calculated for patients in the Global Symplicity Registry (GSR; NCT01534299), a global registry of RDN in patients with uncontrolled hypertension, using baseline office systolic BP, total/HDL cholesterol measurements, diabetic and smoking status, gender, age, and number of baseline anti-hypertensive medications. Patients were separated into 3 groups based on ASCVD risk scores: &lt;10%, ≥10% and &lt;20% and ≥20%. Baseline demographics and 24-hour systolic BP changes at 6 months and 1, 2 and 3 years were compared between groups, as well as rates of adverse events at 3 years. Results Individual ASCVD risk scores were calculated for 1,434 patients in GSR. The median ASCVD risk score was 19.4% and 403 patients had a risk score of &lt;10%, 326 a risk score of ≥10 and &lt;20%, and 705 a risk score ≥20%. Patients with ASCVD risk score ≥20% had a higher baseline office systolic BP, were significantly older, and had higher rates of prior myocardial infarction and/or diabetes (all p&lt;0.0001 compared to patients with lower risk scores). RDN reduced BP similarly across all groups of patients. Changes in 24-hour systolic BP at 6 months and 1, 2 and 3 years are shown in Figure 1. Adverse events at 3 years are shown in Table 1. Adverse events at 3 years ASCVD risk score &lt;10% ASCVD risk score ≥10% &amp; &lt;20% ASCVD risk score ≥20% p-value (N=265) (N=224) (N=468) Death 3 (1.1) 5 (2.2) 41 (8.8) &lt;0.0001 Cardiovascular death 3 (1.1) 2 (0.9) 23 (4.9) 0.0017 Myocardial infarction 6 (2.3) 6 (2.7) 11 (2.4) 0.9513 Stroke 8 (3.0) 9 (4.0) 24 (5.1) 0.3894 Hospitalization for new onset heart failure 4 (1.5) 7 (3.1) 26 (5.6) 0.0194 Values are proportions reported as n (%). Conclusions BP changes after RDN were similar for patients with varying baseline ASCVD risk scores, suggesting uniform BP-lowering efficacy of RDN regardless of patients' baseline CV risk. The impact of baseline risk on clinical event reduction by RDN-induced BP reduction will need to be evaluated in further studies. Acknowledgement/Funding The Global SYMPLICITY Registry is funded by Medtronic.

EFFECTS OF RENAL DENERVATION IN PATIENTS WITH VERSUS WITHOUT CHRONIC KIDNEY DISEASE

Objective: Activity of the sympathetic nervous system (SNS) is increased in hypertensive patients with chronic kidney disease (CKD). In this updated version, we tested the hypothesis whether hypertensive patients with CKD enrolled in the Global Symplicity Registry (GSR) showed different responses in blood pressure (BP) reduction in the short- and long-term follow-up. Design and method: The GSR (NCT 01534299) is a prospective, open-label, international, multicentre observational study for assessment of safety and effectiveness of renal denervation (RDN) among real-world patients treated with the Symplicity™ RDN system (Medtronic, Santa Rosa, CA, USA). Inclusion criteria are age >= 18 years and eligibility for RDN. Office and 24-h ambulatory BP were assessed at pre-specified time-points (12, 24 and 36 months). For the current updated analyses, enrolled patients (N = 1980) were stratified based on baseline estimated glomerular filtration rate in <60 vs. >= 60 ml/min/1.73m2 into with (N = 475) and without (N = 1505) CKD groups. Results: Patients with CKD were significantly older (p < 0.0001) and more likely to be female (p = 0.0027) compared to patients without CKD. At baseline office systolic BP was lower (162.4 ± 26 vs. 165.8 ± 24 mmHg, p = 0.0113), whereas there was no difference in baseline 24-h ambulatory systolic BP (153.6 ± 19 vs. 153.7 ± 18 mmHg, p = 0.9162), in patients with, compared to without CKD. In patients with and without CKD, office as well as 24-h ambulatory BP were significantly reduced after RDN compared to baseline values at all time-points (all p < 0.001). There was a greater office systolic BP reduction in favor of patients without compared to with CKD, whereas no difference in 24-h ambulatory systolic BP reduction after RDN, even after adjustment (Table), was observed.Conclusions: After adjustment for baseline data, BP reduction after RDN showed a disparate response pattern in office and 24-h ambulatory BP reductions in patients with CKD. Data needs to be confirmed by a rigorously conducted, prospective, double-blind, sham-controlled study.

Predictors for success in renal denervation\u2013a single centre retrospective analysis

Renal denervation (RDN) is one of the most frequently used invasive methods for the treatment of arterial hypertension. However, recent randomized sham-controlled studies raised concern about the efficacy and predictability of response. We retrospectively analyzed outcomes of patients, who underwent RDN in our hypertension center between November 2010 and April 2014 and report here outcomes twelve months after procedure based on 24-hours ambulatory blood pressure monitoring. We defined ten-mm Hg decrease in office systolic blood pressure (SBP) as a cut-off for response and looked for possible predictors of this response using binary multiple regression analysis. 42 patients were included. Their mean age was 59.6 ± 9.2 years and 24% were female. Baseline office SBP and diastolic blood pressure (DBP) were 164.1 ± 20.3 and 91.8 ± 12.4 mm Hg respectively. Mean 24 h-SBP significantly decreased from 149.8 ± 13.3 mm Hg to 141.2 ± 14.6 mm Hg. Mean 24 h-DBP significantly decreased from 83.3 ± 11.7 mm Hg to 78.8 ± 11.2 mm Hg. A higher level of mean 24 h-DBP and office DBP was shown to be predictive for response in office BP and a higher level of mean 24 h-DBP for response in 24 h-SBP and 24 h-DBP. Further properly designed randomized trials are warranted to confirm this finding as well as further investigate the role of diabetes mellitus and arterial stiffness in RDN.

IMMEDIATE, SIGNIFICANT DECLINE IN CENTRAL AND PERIPHERAL BLOOD PRESSURE WITH CENTRAL ARTERIAL VENOUS ANASTOMOSIS

Objective: Clinical trials have reported the intermediate and long term reductions of blood pressure (BP) following formation of a central iliac arteriovenous anastomosis (cAVA). We present for the first time, the immediate and day one BP changes after the procedure Design and method: This open-label, multicentre, European registry is enrolling patients with a baseline office systolic BP > 140 mmHg, average daytime ambulatory systolic BP > 135 mmHg, and resistant or uncontrolled hypertension due to multidrug intolerances. Subjects underwent arteriovenous (AV) coupler implantation whilst continuing usual medical management. Results: Creation of a cAVA causes immediate, substantial on table reduction of office and ambulatory BP that persists the following day (Table 1). Furthermore, central systolic BP reduced by 23 ± 22 mm Hg (p < 0.0001), central diastolic BP reduced by 13 ± 13 mm Hg (p < 0.0001), and augmentation index (AI) reduced by 39% (p = 0.0006) 1 day after coupler implantation.Conclusions: A significant, instantaneous and day 1 reduction of peripheral and central BP with profound reduction of AI occurs following creation of a cAVA. This magnitude of BP reduction offers the potential to immediately reduce cardiovascular risk associated with hypertension in contrast to alternative therapies for hypertension in which BP reduction takes places over days to weeks.

Central Iliac Arteriovenous Anastomosis for Uncontrolled Hypertension: One-Year Results From the ROX CONTROL HTN Trial.

URL: http://www.clinicaltrials.gov. Unique identifier: NCT01642498.

BP.10.06] BLOOD PRESSURE RESPONSE TO CATHETER-BASED RENAL SYMPATHETIC DENERVATION IN PATIENTS WITH RESISTANT HYPERTENSION

Objective: The efficacy of catheter-based renal sympathetic denervation (RDN) in terms of blood pressure (BP) reduction has been questioned, while “real-world” data from registries are needed. In the present study we report the complete set of 12 month data on office and ambulatory BP changes as well as the predictors for BP response to RDN from a national registry. Design and method: In 4 Greek hospital centers 79 patients with severe drug resistant hypertension (age: 59 ± 10 years, 53 males, body mass index: 33 ± 5 kg/m2, office BP and 24-hour ambulatory BP were 176 ± 15/95 ± 13 mmHg and 155 ± 14/90 ± 12 mmHg respectively, 4.4 ± 0.9 antihypertensive drugs) underwent RDN and were followed-up for 12 months in the Greek Renal Denervation Registry. Bilateral RDN was performed using percutaneous femoral approach and standardized techniques. Results: Reduction in office systolic/diastolic BP at 6 and 12 months from baseline was -30/-12 mmHg and -29/-12 mmHg, while the reduction in 24-hour ambulatory BP was −16/−9 mmHg and −15/−9 mmHg respectively (p < 0.05 for all). Patients that were RDN responders (85%, n = 58), defined as an at least 10 mmHg decrease in office systolic BP at 12 months, compared to non-responders were younger (57 ± 9 vs 65 ± 8 years, p < 0.05), had higher baseline office systolic BP (176 ± 17 vs 160 ± 11 mmHg, p < 0.05) and 24 h systolic BP (159 ± 13 vs 149 ± 11 mmHg, p < 0.05). Stepwise logistic regression analysis revealed that age, obesity parameters and baseline office BP were independent predictors of RDN response (p < 0.05 for both), but not the type of RDN catheter or the use of aldosterone antagonists. At 12 months there were no significant changes in renal function and no new serious device or procedure related adverse events. Conclusions: In our “real-world” multicenter national registry, the efficacy of renal denervation in reducing BP as well as safety is confirmed during a 12 months follow-up. Moreover, younger age, obesity and higher levels of baseline systolic BP are independently related to better BP response to RDN.