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Aims A comparison influence of renal denervation versus pharmacological treatment with sympathetic nervous system blockers on blood pressure in patients with resistant hypertension. Methods 125 patients with resistant hypertension without comorbidities after a 3-week standardized treatment with Losartan 100 mg, Amlodipine 10 mg and Indapamid 1,5 mg and confirmation of their resistance were randomly assigned into three groups, depending on medication supplemented to previously administered: IM group – selective I1-imidazoline agonist Moxonidine, IIB group – cardioselective beta-blocker Bisoprolol and IIID group – renal artery denervation. Patients were assessed by ambulatory blood pressure monitoring at baseline, 3, 6 and 12 month follow-up. The compliance to drug treatment was confirmed by 8-item Morisky Medication Adherence Scale. Renal denervation was performed with a Symplicity Spyral catheter. Results The mean 24 hour systolic blood pressure (SBP m/24 h) at baseline were 179.0±2.02 mmHg in IM group versus 177.96±2.44 mmHg in IIB group and 176.92±1.97 mmHg in IIID group, p>0.05. Statistically significant dynamics was recorded starting with 3 months of evaluation in all three groups, the group of patients undergoing denervation of the renal arteries demonstrating a net superior effect compared with pharmacological treatment: −6.48±0.81 mmHg in I M group versus −6.2±0.88 mmHg in II B group and −23.28±1.9 mmHg in III D group, p<0.001. The beneficial effect was maintained until the end of the study, when in observational group supplemented with Moxonidine SBP m/24 h were 159.6±1.72 mmHg with a total reduction of −19.9±0.7 mmHg from baseline, in Bisoprolol group −164.08±1.93 mmHg with a reduction of −13.88±1.13 mmHg and 141.76±0.77 mmHg in renal denervation group with a total reduction of −35.16±2.23 mmHg, p<0.001. The mean 24 hour diastolic blood pressure (DBP m/24 h) increased at baseline in all three groups (105.52±1.28 mmHg in IM versus 108.6±1.6 mmHg in IIB and 107.24±0.92 mmHg in IIID, p>0.05) similar to SBP m/24 h noted a significantly reduction at 3 month follow-up: −4.8±0.96 mmHg in IM group versus −3.64±0.47 mmHg in IIB group and −12.08±0.63 mmHg in IIID group, p<0.001. The maximum reduction in DBP m/24 h were registered at 12 month follow-up, a comparative analyses of dynamics between groups showing a presence of statistical difference due to superiority of renal denervation treatment in amelioration of this parameter: −13.68±0.83 mmHg in IM group versus −10.72±0.64 mmHg in IIB group and −20.2±1.28 mmHg in IIID group, p<0.001. Conclusions The application of all three treatment regimens has been shown to be effective in reducing SBP and DBP values m/24 hours in patients with resistant hypertension, with a superior but comparable effect of Moxonidine to Bisoprolol and the absolute superiority of renal denervation treatment versus both pharmacological treatment regimens. Funding Acknowledgement Type of funding source: None

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Agency for Research an Development OnBehalf HIPERDIAB Background Increased blood pressure is considered the major determinant for structural alterations of the left ventricle resulting in increased myocardial mass and pathological remodeling. Renal denervation is a novel treatment for hypertensive patients with promising results on blood pressure levels. Purpose Evaluation of impact of renal denervation treatment on indices of left ventricular remodeling in patients with resistant hypertension. Methods 75 patients with resistant hypertension  after a 3-week standardized treatment with Losartan 100 mg, Amlodipine 10 mg and Indapamid 1,5 mg were randomly assigned into three equal groups, depending on medication supplemented to previously administered: IM group -  Moxonidine, IIB group - Bisoprolol and IIID group – renal artery denervation (RDN). Patients were assessed by echocardiographic exam at baseline and 6 months follow-up. Renal denervation was performed with a Symplicity Spyral catheter. Results Increased at the baseline in all three groups (170,96 ± 11,69 g/m2  in IM versus 156,5 ± 11,08 g/m2  in IIB and 164,94 ± 9,61 g/m2  in IIID groups) left ventricular mass index at 6 months of evaluation noted a statistically authentic reduction in all three groups, the group of patients treated with Moxonidine and RDN having a comparable and superior effect to the group treated with Bisoprolol (159,02 ± 10,34 g/m2 versus 150,5 ± 10,51 g/m2 and 149,15 ± 9,31 g/m2 in IM, IIB and IIID groups, p > 0,05). Simultaniously with the regression of left ventricular myocardial hypertrophy all three treatment regimens induced the improvement of its geometry, renal denervation group demonstrated a superior effect in ameliorating of this parameter (Tab.). Conclusion The data obtained confirmed the benefit of RDN treatment in patients with resistant hypertension in inducing reverse-remodeling of the LV, the beneficial effect being superior to both pharmacotherapeutic regimens. Geometric pattern of the left ventricle Group IM Group IIB Group IIID χ2 p baseline Concentric remodeling 5 (20%) 5 (20%) 4 (16%) 0,71 > 0,05 Concentric hypertrophy 13 (52%) 15 (60%) 14 (56%) Excentric hypertrophy 7 (28%) 5 (20%) 7 (28%) Normal geometry - - - 6 months Concentric remodeling 3 (12%) 7 (28%) 7 (28%) 4,61 < 0,05 Concentric hypertrophy 13 (52%) 13 (52%) 10 (40%) Excentric hypertrophy 8 (32%) 5 (20%) 5 (20%) Normal geometry 1 (4%) - 3 (12%)

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Objective: Patients with resistant hypertension and type 2 diabetes mellitus (DM) accelerate the subclinical brain damage and the age-related brain atrophy, which leads to a more rapid decrease in cognitive functions. Brain MRI can detect expansion of liquor spaces and white matter lesions (PWMLs), which are patterns of brain atrophy. Renal denervation (RDN) is an effective treatment for resistant hypertension (RHTN), but the key question is whether RDN can slow the progression of brain damage. The aim of this study was to evaluate the effect of renal denervation on the MRI- sing of brain damage in patients with RHTN with type 2 DM over a 3-year follow-up. Design and method: The study included 17 diabetic patients with RHTN (mean age 61,3 ± 6.2 years; 9 males, mean 24 hour (systolic/diastolic) blood pressure (BP) 161.3 ± 19.4/82.2 ± 13.5 mmHg, HbA1c 7 ± 1,2%) from single-arm prospective interventional study (NCT02667912 on ClinicalTrial.gov) in whom 1.5T magnetic resonance imaging (MRI) of the brain and 24-hour BP monitoring were performed at baseline and an annually for 3 years follow up. We measured linear dimensions of liquor spaces (subarachnoidal spaces (SAS), lateral ventricles (LV), both III and IV ventricles) and calculated the number of focal white matter lesions. Periventricular white matter lesions (PWMLs) were evaluated semi-quantitatively on a scale of 0 to 4. On average, patients were taking 4.3 ± 1.0 antihypertensive drugs and were instructed not to change their medication regimen for the duration on the study. The mean number of ablations was 13 ± 1.8 (10–16). Results: Three years after RDN, there was a significant decrease in the average 24-hour systolic/diastolic BP by 14.1/8.6 mm Hg (p = 0.03/0.04). The linear dimensions of liquor spaces (SAS, LV, both III and IV ventricles), number of focal white matter lesions, as well as the mean PWMLs score did not change (p > 0.05). Conclusions: This is the first study to demonstrate that RDN can prevent progression of brain damage in diabetic patients with RHTN during 3 years follow-up and therefore has a potentially beneficial effect on the brain.