Background: Historical reports on surgical renal denervation consistently describe renal plexus as a triangle or fan-like structure converging at the kidney gate. Following that anatomy, we developed a distal mode of radiofrequency renal denervation (RDN) mainly in segmental branches of the renal artery and confirmed its superior efficacy over the conventional main trunk procedure in a 6-months double-blind randomized controlled trial (NCT02667912). To assess the long-term effects of distal RDN we extended the follow-up of our study to three years. Methods: BP, serum creatinine, eGFR were measured one and three years after randomization; major adverse renal events were assessed over the entire study period. The blinding was maintained over the entire three-year study period. Findings: Of 55 randomized patients, 47 (23/24, distal/main trunk RDN, respectively) were assessed at one year and 39 (21/18) at three years post-procedure. Twenty-four-hour ambulatory systolic BP remained powerfully lowered after distal RDN both at one- and three-years assessments(mean change from baseline: -18.0, 95% CI -27.6 to -8.5; p<0.05 and -16·9, 95% CI -27·3 to -6·5; p<0·05, mmHg, respectively. This was accompanied by a moderate drop in eGFR at one year: -8·9 ml/min/m2, 95% CI -14·8 to -3·1; p<0·05, which, however, subsequently decreased in size at three years: -6·5, 95% CI -13·2 to 0·3; p>0·05. After main trunk RDN, the decrease of 24h systolic BP was quite moderate at one year: -12·1, 95% CI -19·2 to -5·0; p<0·05, and further weakened at three-year assessment: -8·5, 95% CI -19·7 to 2·2; p>0.05. eGFR was almost unchanged at one year: -1·3, 95% CI -6·6 to 4·0; p>0·05, but significantly decreased at three years: -5·0, 95% CI -9·6 to -0·3; p<0·05. Interpretation: Our data demonstrate the durable strong BP-lowering efficacy and favorable long-term renal safety of distal RDN.

Hyperactivity of the sympathetic nervous system is one of the basic mechanisms in the development of arterial hypertension (AH). Transcatheter renal artery denervation is aimed to destroy the renal sympathetic afferent and efferent nerves to achieve a sustained reduction in blood pressure. Since 2017, all II generation studies have demonstrated that sympathetic denervation provides clinically significant BP reduction. Russian Medical Society for Arterial Hypertension (RMSAH) experts consider SD as a possible addition to the antihypertensive strategy in patients with uncontrolled AH and recommend denervation of the renal arteries in registers and clinical trials. On the basis of existing randomized clinical trials, as well as the experience of radiofrequency denervation in Russia, the experts of RMSAH present a consensus and view of the current situation in the field of renal denervation.

Objective: To evaluate efficacy and safety of anatomically optimized distal renal denervation (RDN) in segmental branches of renal artery. Design and method: We performed a double blind, randomized control study of the efficacy and safety of distal RDN versus conventional main trunk treatment in patients with true resistant hypertension (NCT02667912) with 3 year follow-up period. The efficacy of the RDN was evaluated by changes in ambulatory and office BP at 6, 12 and 36 month. The safety was assessed by a number of procedure-related adverse events, changes in the 24-h protein excretion, serum creatinine and eGFR during the same time periods. Results: Of 55 randomized patients who undergone RDN (28 - distal denervation vs 27 - main trunk treatment) 51 completed 6 month (27 vs 24), 47 - 12 month (23 vs 24), and 39 - 36 month follow-up (21 vs 18). There was a powerful significant decrease in 24-h mean ambulatory systolic BP at 6 month after distal RDN that was, also, maintained throughout the follow-up, and remained statistically significant at the end of the study, -21.1 (95% CI -28.9;-13.3), -18 (95% CI -27.6;-8.5), -16.9 (95% CI -27.3;-6.5), mmHg, at 6, 12, and 36 month, respectively. In group of conventional main trunk treatment the same BP decreased substantially less at all study periods, and lost significance at 36 month. -10.3 (95% CI -17.8;-2.8), -12.1 (95% CI -19.2;-5.0), -8.7 (95% CI -19.7;2.2). Other ambulatory BP indices changed accordingly. eGFR decreased in group of distal RDN at 1 year post-procedure -8.9 (95% CI -14.8;-3.1), mL/min/sq.m, however, slightly increased during next 2 years with finally non-significant change at the end of the study, -6.5 7 (95% CI -13.2;0.3). In contrast, in group of main trunk treatment eGFR remained unchanged during 1st year, -1.3 (95% CI -6.6;4.0) but progressed to statistically significant decrease at 3-year post-procedure, -5.0 (95% CI -9.6;-0.3). Conclusions: Anatomical optimization of renal denervation by redistributing treatments to segmental branches of renal artery produces a durable increase in the efficacy of the intervention without additional risk to the kidney.

Симпатическая гиперактивность нервной системы является одним из основных механизмов в развитии артериальной гипертонии. Транскатетерная денервация почечных артерий предназначена для разрушения почечных симпатических афферентных и эфферентных нервов для достижения устойчивого снижения артериального давления. Начиная с 2017 г. все исследования с применением устройств II поколения продемонстрировали, что ренальная денервация (РДН) обеспечивает клинически значимое снижение артериального давления. Эксперты Российского медицинского общества по артериальной гипертонии (РМОАГ) рассматривают РДН как возможное дополнение к антигипертензивной стратегии у пациентов с неконтролируемой артериальной гипертонией и рекомендуют проведение денервации почечных артерий в рамках регистров и клинических исследований. На основании существующих рандомизированных клинических исследований, а также опыта проведения РДН в России эксперты РМОАГ представляют консенсус и взгляд на современную ситуацию в области РДН.

BACKGROUND:Effective treatment of uncontrolled hypertension using catheter-based percutaneous renal denervation may depend strongly on the anatomic strategy applied when delivering therapy. We hypothesized that concentering renal denervation treatment in the distal region of the artery would improve clinical response. METHODS AND RESULTS:We conducted a single-center, double-blind, randomized, controlled, and parallel group study (ClinicalTrials.gov NCT02667912). Fifty-one treatment-resistant hypertensive patients meeting guideline indications were randomized either to 'conventional' treatment restricted to the main renal artery (n = 26) or to 'distal' treatment applied mainly in the distal branches beyond the main bifurcation (n = 25). Computer-based treatment assignment was performed in the catheterization laboratory at the time of the procedure by the interventional radiologist and remained unknown to patients, investigators, and other outcomes assessors for the entire study period. Six months after randomization, the distal therapy group (n = 24) had a significantly greater decrease in the primary outcome, 24-h mean ambulatory SBP, as compared with the conventionally treated group (n = 21): -22.6 ± 20.0 vs -9.4 ± 18.7 mmHg; P less than 0.05. No major safety issues were observed in either group. CONCLUSION:Percutaneous renal denervation treatment was significantly less effective at lowering 24-h blood pressure in treatment-resistant hypertensive patients when therapy was applied conventionally in the trunk of renal artery as compared with when applied to distal segmental branches. This observation is in accordance with previous surgical and anatomical findings showing that most renal nerve fibers are distant from the lumen proximally and become available for endovascular treatment mainly in the distal portion of the vessel.

In recent years, an increasing attention is paid to the development of vascular fibrosis in patients with arterial hypertension (AH). Particular importance is given to changes in the concentrations of matrix metalloproteinases (MMPs), which play a key role in the development of connective tissue disorders. As of today, research data on the levels of the MMP(2 and the MMP(9 in hypertensive patients and their changes due to treatments remain controversial. Data concerning the impact of renal sympathetic denervation on the changes in the MMPs concentrations in patients with resistant hypertension are unavailable. The objectives of the study were (1) to determine the contents of matrix metalloproteinases 2 and 9 and of their tissue inhibitor TIMP(1 in patients with resistant hypertension before and 6 months after the transcatheter renal artery sympathetic denervation; (2) to compare these parameters in cases of effective and ineffective invasive treatment; and (3) to study the interaction between the enzymes concentrations and blood pressure levels, including pulse pressure levels.

The aim of the study was to evaluate long-term antihypertensive and cardioprotective efficacy of renal denervation in patients with drug(resistant arterial hypertension. The study excluded patients with symptomatic hypertension, multiple renal arteries when the diameter of one or more arteries was less than 3 mm, and patients with severe kidney disease stage 4–5. According to these criteria, 73 people were selected for renal denervation procedure. Comparison of the initial data with the values obtained after 12 months demonstrated the presence of a significant continuous antihypertensive effect with blood pressure decrease by –29.1/–14.8 mm Hg in the office blood pressure levels and by –12.9/–7.8 mm Hg according to 24(h monitoring. The study showed a decrease in the myocardial mass of the left ventricle in individuals who initially had more pronounced left ventricular hypertrophy.

Objective: A failure of endovascular renal denervation (RDN) as a series of point treatments equally distributed within main trunk of renal artery (Symplicity and other methods) was easily predictable. It may only be effective if all renal nerves closely follow the course of renal artery (RA) from aorta to the kidney. However, surgical studies demonstrated that proximally most renal nerves go at a distance from RA and join mainly its distal part. To evaluate whether denervation treatment in distal part of RA is more effective than conventional RDN. Design and Method: We developed a distal mode of RDN mainly in segmental branches of RA and compared its efficacy and safety to those of conventional RDN in a single-center double-blind randomized controlled parallel group study (ClinicalTrials.gov NCT02667912). Inclusion criteria: both genders, 18–80 years, office systolic BP ≥ 160 or diastolic BP ≥ 100 mmHg despite ≥3 antihypertensive drugs including a diuretic, written informed consent. Exclusion criteria: secondary hypertension, 24h-mean systolic BP < 135 mmHg, eGFR < 30 mL/min/m2, extended RA disease, comorbidities causing high risk of the intervention (investigator's assessment). Randomization was done in Cath lab using computer-generated random sequence and remained unknown to patients and outcome assessors. Primary outcome was the between-group difference in baseline-to-6-month change of 24h-mean systolic BP. Results: Of 45 patients enrolled in the study 24 undergone distal RDN and 21 – conventional RDN. Of them 41 (89%) completed 6 months follow-up and were included in per-protocol analysis. The 24 h mean systolic BP decreased powerfully in the distal treatment group (n = 23): −22.4 (SD 20.5) mmHg, p < 0.0001 and only slightly - in conventional RDN group (n = 18): −8.7 (SD 18.8), p = 0.06. The difference between the groups was statistically significant, p = 0.036. Conclusions: Distal RDN is superior to conventional mode of the intervention, however, currently may only be done with ablation catheters. Complex devices (baskets, balloons) need redesigning for use in segmental branches of RA.

The aims of the study were to evaluate the effects of renal sympathetic denervation (RSD) on the heart and to identify the predictors of RSD efficacy in patients with resistant arterial hypertension. The study comprised 60 RSD patients (54.6 ± 9.5 years) who received full-dose antihypertensive therapy (4.1 drugs) including diuretics. Initially, 58.6 % of patients had abnormal left ventricular (LV) diastolic function. All patients received echocardiography before and 24 weeks after RSD. Renal sympathetic denervation was achieved through the endovascular radiofrequency ablation (RFA) of the renal arteries. Drug therapy continued for the entire period of observation. After RSD, all patients were retrospectively assigned to two groups: group 1 comprised patients (n = 22; 36.7 %) in whom the myocardial mass (MM) of the left ventricle decreased by more than 10 g after RSD; group 2 comprised patients (n = 38; 63.3 %) in whom LV MM increased or decreased by less than 10 g. Anthropometry, arterial blood pressure, heart rate, therapy, and LV end-diastolic dimensions (EDD) were comparable in these groups. After RSD, the values of office blood pressure significantly decreased and MM regressed by more than 10 g in 36.7 % of patients; LV diastolic function normalized in 31 % of patients, and diastolic dysfunction improved in 14 % of patients. The study found the associations between the initial LV wall dimensions and LV MM changes. Unlike LV EDD, arterial blood pressure, or heart rate, the initial values of LV wall thickness predicted LV MM regress. Trial registration: #NCT01499810 https://clinicaltrials.gov/ct2/show/NCT01499810.

Background. The high prevalence of cardiac damage in resistant hypertensive patients signifcantly increases the risk of cardiovascular complications. Despite the antihypertensive effcacy of renal denervation (RDN), the cardioprotective effect has not been suffciently studied. Objective. To study the changes in left ventricular mass (LVM) and volume of myocardial damage after the RDN and to detect a possible connection of the studied parameters with blood pressure (BP) reduction after RDN. Design and methods. RDN was applied to 84 patients with resistant hypertension. Initially, at 6 and 12 months after treatment, patients underwent the measurements of the “offce” BP, 24-h BP, echocardiography and cardiac contrast-enhanced magnet-resistance tomography. Results. At baseline, “offce” BP averaged 175,3 ± 22,1 / 100,4 ± 16,1 mmHg and the prevalence of left ventricular hypertrophy (LVH) was 84,5 %. “Offce” BP reduced signifcantly at 6 month by –27,5 (–74,0; 12,0) / –14,2 (–39,4; 10,3) mmHg (p < 0,001), at 12 month by –31,6 (–78,7; 8,3) / –15,5 (–43,3; 10,2) mmHg (p < 0,001). 24-h BP reduced signifcantly at 6 month by –13,0 (–45,2; 17,6) / –6 (–27,8; 8,9) mmHg (p < 0,001), at 12 month by –14,3 (–52; 25) / –7,3 (–26; 15,0) mmHg (p < 0,001). At 12 month after RDN LVM decreased by 6,9% (p = 0,015), LV mass index by 5,5 % (p = 0,020). According to MR study, subendocardial damage was detected in 100% of patients in the absence of coronary atherosclerosis. A volume of subendocardial damage signifcantly reduced by 29 % at 6 month (p = 0,031) and by 41,4% at 12 months after RDN (p = 0.008). LVM reduced signifcantly by 18,3 % (р = 0,008). LVM also reduced signifcantly in non-responder’s group at 6 month after RDN (р = 0,046). The regression of subendocardial damage correlated with the change in systolic BP at 12 months after RDN (р = 0,034). There was no signifcant correlation between LVH regression and baseline BP and its change after RDN. Conclusions. One year after RDN, LVH decreased independently from the BP change. Subendocardial damage was detected in 100% patients, regressed at 6 months after RDN and correlated with the regression of systolic BP at 12 month after the RDN.