Treatment Of Resistant Arterial Hypertension Research Articles

Baxdrostat and finerenone: new aldosterone synthase-aldosterone-mineralocorticoid receptor hormonal system inhibitors for the drug treatment of resistant arterial hypertension

Resistant arterial hypertension is characterized by failure to control target blood pressure despite long-term use of optimal or maximum tolerated doses of three different antihypertensive drugs, including diuretic. Patients with resistant hypertension are included in a group of people at high risk of cardiovascular and renal complications, including accelerated progression of chronic kidney disease with a more rapid transition to the final stage of the disease. Resistant hypertension is based on a salt-sensitive, volume-dependent form of hypertension, which usually occurs against the background of increased aldosterone production and normal or even decreased renin plasma activity. A key role in its formation is played by an increase of sodium reabsorption in the kidneys, associated with excessive activity of aldosterone-sensitive epithelial sodium channels (ENaC), which control the reabsorption of this ion in the distal segments of the nephron. Its assumed that in this pathological process, in addition to aldosterone, is also involved the small Rho GTFase Rac1 — regulatory G-protein, which can enter into a direct ligand-independent interaction with mineralcorticoid receptors, performing the function of a powerful nonsteroidal activator of the transmission of their intracellular signals. Based on controlled, randomized clinical trials, the optimal fourth drug to overcome resistance in such patients is the steroid mineralcorticoid receptor antagonist spironolactone. However, the inclusion of this drug in antihypertensive therapy not only fails to control blood pressure in a significant proportion of patients with resistant hypertension, but also significantly increases the risk of hyperkalemia, especially in people with impaired renal function. The review presents data on the pharmacodynamics and pharmacokinetics of new inhibitors of aldosterone synthase-aldosterone-mineralocorticoid receptor hormonal system baxdrostat and finerenone, as well as the results of clinical studies assessing the clinical effectiveness and safety profile of these drugs in patients with resistant hypertension.

The Role of Immunohistochemistry in Managing Clinical Hypertension and Other Chronic Inflammatory Processes

Immunohistochemistry (IHC) is a pivotal technique in the visualization of specific proteins within tissue samples, leveraging antigen-antibody interactions to elucidate protein presence, distribution, and abundance. In clinical hypertension, IHC is instrumental in unraveling disease mechanisms, identifying biomarkers, and fostering targeted therapies. This review delves into IHC’s contributions to managing hypertension by examining its role in understanding the pathophysiology and identifying key proteins like those in the renin-angiotensin-aldosterone system. Elevated angiotensin II type 1 receptors in vascular walls, detected via IHC, correlate with hypertension and vascular remodeling. Additionally, IHC identifies inflammatory markers such as interleukin-6 and tumor necrosis factor-alpha, linking chronic inflammation to hypertension. The technique is vital for discovering biomarkers like endothelial nitric oxide synthase and vascular endothelial growth factor, essential for assessing endothelial function. IHC also detects oxidative stress markers, aiding in understanding oxidative mechanisms in hypertension. Evaluating antihypertensive therapies at a molecular level, IHC shows how interventions affect protein expression and vascular health, guiding therapeutic strategies. By revealing proteins differentially expressed in hypertensive tissues, IHC identifies new therapeutic targets, enhancing treatment efficacy. Furthermore, this review explores the application of IHC in other chronic inflammatory conditions, such as rheumatoid arthritis and inflammatory bowel disease, highlighting its broader relevance in disease management. Recent advancements include the development of new drugs targeting specific molecular pathways, such as endothelin 1 receptor antagonists like aprocitentan, approved by the FDA in March 2024 for the treatment of resistant arterial hypertension. Overall, IHC significantly advances both research and clinical practice, promising improved health outcomes through continued methodological advancements.

Aprocitentan: a novel option for treatment of resistant arterial hypertension.

Aprocitentan: a novel option for treatment of resistant arterial hypertension.

Renal denervation for the management of refractory ventricular arrhythmias

Abstract Background While catheter ablation (CA) has proven effective in managing ventricular arrhythmias (VA) associated with structural heart disease, a portion of patients continue to experience refractory VA despite medical treatment and multiple CA procedures. In such cases, additional techniques, such as autonomic neuromodulation, have been explored. Renal denervation (RDN), traditionally performed for the treatment of resistant arterial hypertension, inhibits the afferent renal sympathetic pathway, leading to reduced efferent sympathetic overactivation on a systemic level. Due to this mechanism, it has also been studied for the management of arrhythmias, including atrial fibrillation and VA, with favorable results. Objective To assess the effectiveness and safety of RDN for the management of refractory VA storms in high-risk patients. Methods A retrospective analysis of RDN procedures for electrical storms, conducted at a tertiary center between February 2020 and September 2023. We analyzed baseline patient characteristics, procedural details, and acute complications. Recurrence of VA after RDN was assessed at one and six months. Results A total of 7 patients underwent RDN for the treatment of refractory VA. The mean age was 56 ± 10 years (6 male). The primary diagnosis was ischemic cardiomyopathy (n=5), with a mean left ventricular ejection fraction (LVEF) of 20 ± 5%, and no history of resistant arterial hypertension. All patients had an implantable cardioverter-defibrillator (ICD) (two with concomitant resynchronization therapy). Five patients had undergone previous endocardial VA ablation. Of the two patients without prior VA ablation, one had a contraindication because of a large left ventricle thrombus, and the other was submitted to an electrophysiological study, but without inducible ventricular tachycardia. In the four weeks before RDN, patients exhibited a mean of 12 ± 18 sustained VA episodes, meeting the criteria for electrical storm (3 ≥ episodes in 24h). During the procedure, there was a mean of 7 ± 8 radiofrequency applications in the right renal artery and 6 ± 10 in the left renal artery. No acute complications were observed. One month after the procedure, VA episodes were reduced to a mean of 0 ± 1, with only two patients experiencing recurrent VA. After six months, the absence of VA recurrence remained consistent, with only one patient experiencing new episodes. There were no deaths during this period. Conclusion In our pilot study, RDN appeared to be a safe and effective treatment for the management of VA.VA episodes before and after RDN

#2665 EFFECT OF RENAL DENERVATION ON THE PLASMA LEPTIN CONCENTRATION IN PATIENTS WITH RESISTANT HYPERTENSION

Abstract Background and Aims Leptin is mainly produced by adipose tissue and has hypertensinogenic properties. In patients with arterial hypertension, plasma concentration of leptin is higher than in healthy subjects. Percutaneous ablation of the sympathetic nervous system fibers located in the wall of the renal arteries by radio frequency waves (renal denervation - RDN), was introduced as a method of invasive treatment of resistant arterial hypertension. The aim of this single center, interventional, clinical study was to assess the effect of RDN on the plasma leptin concentration in patients with resistant arterial hypertension. Method Eighteen patients (9 women, 9 men) aged 53.2±6.5 years with resistant hypertension who underwent RDN using Simplicity catheters (Medtronic, Inc., Northridge, CA) were enrolled in the study. Plasma leptin concentration was determined using the Human Leptin RIA HL-81K (Linco Research, Inc., Missouri, USA) before RDN denervation and 6 months after RDN. Additionally, patients were divided into two subgroups: responders (systolic and diastolic blood pressure - BP reduction 6 months after RDN >25 mmHg and >12 mmHg, respectively; n=9) and low responders (systolic and diastolic BP reduction 6 months after RDN ≤25 mmHg and ≤12 mmHg, respectively; n=9). Results Systolic and diastolic BP was significantly reduced after RDN (196.6±28.2 and 162.9±15.6; p<0.001 and 117.9±26.4 and 90.7±8.6 mmHg; p<0.001, respectively). Body mass index (BMI) before RDN and 6 months after RDN was similar (31.0±4.4 and 31.3±4.4 kg/m2; P = .8, respectively). Mean plasma leptin concentration before RDN and 6 months after RDN did not change significantly in the entire studied group (27.2±14.3 and 24.6±13.1 [ng/mL], NS), as well as both in responders (29.9±14.4 and 28.2±12.9 [ng/mL, NS) and low-responders subgroups (24.4±14.7 and 21.0±12.9 [ng/mL], NS), respectively. Conclusion Renal denervation is effective in the treatment of patients with resistant hypertension, however this effect is not mediated by the influence on plasma leptin concentration.

745 INTERDISCIPLINARY EVALUATION IN RESISTANT ARTERIAL HYPERTENSION

Abstract Background Arterial hypertension is a complex and in most cases multifactorial pathology. Despite the numerous pharmacological treatments available, it is estimated that in Europe only 25%-39% of hypertensive patients achieve adequate blood pressure (BP) control. Renal arteries denervation (RDN) is an additional therapeutic weapon, complementary to Optimal Medical Therapy (OMT) in patients with resistant or refractory primary (or essential) arterial hypertension. In order to improve patients management and select those who are eligible for renal denervation, our Center has established the Interdisciplinary Group for the Treatment of Resistant Arterial Hypertension (G.I.T.I.A.R.), including Cardiologists, Nephrologists, Internists and Geriatricians. Methods From January 2018 to July 2022 the G.I.T.I.A.R. held twelve meetings evaluating 62 patients with resistant or refractory forms of arterial hypertension, contraindications or intolerance to antihypertensive drugs, suspected secondary or pseudoresistant forms (i.e. linked to poor patient compliance, drugs and/or inadequate dosages, concomitant intake of substances with hypertensive effect, incorrect measurements). For each of them, medical therapy was optimized and the need for second level diagnostic tests, multi-specialist follow-up and RDN candidacy were assessed. After three, six, twelve months and then annually following RDN, the patients underwent clinical and multi-specialist evaluation (where deemed appropriate), blood tests monitoring and 24-hour ambulatory blood pressure monitoring (ABPM). Results Of the 62 patients evaluated by the G.I.T.I.A.R., 64.5% (n=40) were male. The mean age at the time of evaluation was 64 years (range 18-87). After the first collegial discussion, 46.8% (n=29) have been declared eligible for RDN, while 53.2% (n=33) of the patients was initially rejected: 39.4% of these (n=13) for suspected or ascertained secondary hypertension, 12.1% (n=4) for the possibility of further optimization of medical therapy, 48.5% (n=16) for the presence of inclusion or exclusion criteria of ongoing studies design. Among the excluded patients, six presented moderate renal artery stenosis on non-invasive imaging: in two patients (33.3%) the stenosis turned out to be hemodynamically significant on angiographic and functional evaluation (Pd/Pa measurement), so renal angioplasty was performed; RDN was performed in the remaining 66.7% (n=4), in which a hemodynamic significance of the stenosis was excluded. Of the subgroup who had optimized medical therapy, one patient (25%) was subsequently referred to RDN for failure of all pharmacological strategies, while 3 of 4 (75%) achieved adequate BP control. Conclusions Resistant arterial hypertension is associated with an increased risk of development and progression of cardiovascular and renal diseases, with a significant impact on mortality and morbidity. Renal denervation has proved to be an effective and safe therapeutic strategy, complementary to OMT, whose selection of the ideal patient actually represents one of the greatest challenges. The integrated multidisciplinary approach improves the management of the hypertensive patient, the individualization of therapy and allows the identification of subjects who may benefit from RDN.

Diagnostics and treatment of resistant arterial hypertension

Resistant arterial hypertension is diagnosed when three antihypertensives assignment does not result in achieving target blood pressure, which for most patients is the level below 140/90 mm Hg, wherein one of the medicaments must be diuretic and all drugs must be assigned to optimal or maximum tolerated doses. Despite the high prevalence of resistant arterial hypertension, the lack of blood pressure control is often associated with an inadequate selection of antihypertensive therapy, blood pressure misjudgement or failure of patients to medical recommendations. Therefore, before carrying out diagnostic measures necessary to consistently assess the adequacy of patients receiving therapy that inherent in the definition of RAH and exclude pseudoresistance.

Diagnosis and treatment of aldosterone-producing adenoma in a young patient: a clinical case

The prevalence of primary hyperaldosteronism (PHA) among individuals with essential arterial hypertension is about 5 to 10%. We present a clinical case of a 32 year old male patient, who despite the full clinical picture of PHA, was managed in primary care setting with the diagnosis of myalgia and treatment-resistant arterial hypertension. The article discusses clinical and laboratory parameters of the patient with the diagnosis of unilateral aldosteroma and the efficacy of its treatment. The generally accepted algorithm of PHA diagnosis with unilateral aldosterone-producing adenoma in young patients does not involve comparative selective blood sampling from adrenal veins. This accelerates the differential diagnosis and facilitates the decision to undertake surgery. This simplified diagnostic algorithm was successfully applied in the patient. Reasonable surgical intervention has led to the recovery of the patient. Awareness of various medical specialties of the up-to-date information on PHA and wide implementation of its screening into clinical practice, first of all, assessment of aldosterone-renin ratio, would allow for detection of the disease as early as possible and prevention of the development of life-threatening cardiovascular complications.

Цукровий діабет і артеріальна гіпертензія

В огляді проведений аналіз літературних джерел, присвячених сучасному стану проблеми цукрового діабету (ЦД) і артеріальної гіпертензії (АГ). За даними Всесвітньої організації охорони здоров’я, АГ та ЦД 2-го типу після ожиріння є одними з провідних чинників серцево-судинного ризику, які найбільш поширені серед населення світу. За останні 30 років поширеність АГ зменшилась до однієї четвертої частини населення світу, але захворюваність на ЦД зросла з 4,7 до 8,5%, і прогноз на майбутнє свідчить про подальший драматичний приріст. Покращення обізнаності, лікування та контролю цих захворювань є основною метою глобальної системи охорони здоров’я. Поширеність АГ у хворих на ЦД 2-го типу до трьох разів вища, ніж у пацієнтів без ЦД, а поєднання АГ і ЦД суттєво збільшує ймовірність розвитку серцево-судинних захворювань. Несприятливий взаємозв’язок цих двох станів, прискорюючи процеси атеросклерозу, може спричинити негативні патофізіологічні зміни серцево-судинної системи. Крім того, відомо, що кардіоваскулярна автономна нейропатія, яка виникає в результаті пошкодження вегетативних нервових волокон, що іннервують серце та судини, є вагомим ускладненням ЦД 2-го типу, особливо за наявності системної АГ. Зокрема, аналізуються питання, пов’язані із спільними патофізіологічними механізмами, основними системними та метаболічними чинниками, що можуть сприяти коморбідності ЦД і АГ. Наведені класифікація, особливості діагностики АГ, особливості оцінки ураження органів, опосередкованого АГ. Аналізуються питання, пов’язані з основними підходами до лікування артеріальної гіпертензії при цукровому діабеті; використанням блокаторів ренін-ангіотензинової системи, блокаторів кальцієвих каналів, тіазидних і тіазидоподібних діуретиків, блокаторів бета-адренергічних рецепторів, альфа-адреноблокаторів, антагоністів мінералокортикоїдних рецепторів; особливостями комбінованої терапії та лікування резистентної артеріальної гіпертензії.

Резистентная артериальная гипертензия

The review provides modern data on the examination and treatment tactics of patients with resistant arterial hypertension (RAH). The prevalence of RAH is about 10–15%, with a significant proportion of pseudo-resistance cases associated with low adherence to therapy, inaccurate blood pressure measurement technique, and increased arterial stiffness in the elderly. In patients with RAH, it is necessary to exclude secondary hypertension, of which drug hypertension associated with the use of nonsteroidal anti-inflammatory drugs, nasal sympathomimetics, oral contraceptives, as well as those caused by obstructive sleep apnea syndrome or primary hyperaldosteronism are prevalent. Secondary hypertension is often asymptomatic, therefore, additional examination is required for patients without the classic signs of these diseases. Pharmacotherapy of RAH includes a high-dose combination of antihypertensive drugs. In the first instance, first-line drugs (the renin-angiotensin system blockers, calcium antagonists, thiazide diuretics) should be combined with mineralocorticoid receptor antagonists, which have a good evidence base (PATHWAY-2, ReHOT studies), and then other reserve drugs. The study of interventional methods for the treatment of RAH continues. To date, the effectiveness of renal denervation has been proven. The study of the method of carotid baroreflex amplification continues. Keywords: arterial hypertension, resistant arterial hypertension, secondary arterial hypertension, antihypertensive therapy, renal denervation For citation: Rodionov AV, Yudin IG, Fomin VV. Resistant arterial hypertension. Consilium Medicum. 2021; 23 (1): 28–31. DOI: 10.26442/20751753.2021.1.200697

1418Adverse effects of spironolactone in long-term treatment of resistant arterial hypertension

Abstract Background Spironolactone is recommended as a fourth line antihypertensive drug by current hypertension guidelines. This drug had relatively few adverse effects in short term clinical trials, but data about their occurrence during long-term treatment of resistant hypertension are scarce. Purpose To evaluate the occurrence and type of adverse effects of spironolactone during long-term treatment and their possible clinical and laboratory predictors. Methods We prospectively followed 274 patients with resistant arterial hypertension who started treatment with spironolactone between September 2007 and December 2016. The duration of spironolactone use, its dose, the incidence of adverse events, blood pressure, and laboratory findings were recorded at baseline and during the last clinical examination. Results Patients were followed for an average of 35 (± 29) months, the mean dose of spironolactone was 27.5 mg/day. Adverse effects occurred in 72 patients (26.3%) and in 61 (84.7%) lead to discontinuation of spironolactone. The most common adverse reactions were gynaecomastia (30.6%), hyperkalaemia (30.6%) and symptomatic hypotension (26.4%). The mean duration of spironolactone treatment before their occurrence was 25 (± 27) months. According to the Kaplan-Meier curve, the median for the incidence of adverse events would be 97 months (91.5–102.5 months), i.e. 50% of patients could be treated with no adverse events for more than 8 years. Adverse events were more common in the elderly (hazard ratio – HR 1.38, P=0.007), patients with higher baseline serum creatinine (HR 1.12, P=0.035) and patients taking angiotensin receptor blockers (HR 1.65, P=0.040). Kaplan-Meier estimate – adverse events Conclusion During long-term treatment of resistant hypertension with spironolactone, more than a quarter of patients experience adverse reactions that usually require discontinuation of spironolactone. Acknowledgement/Funding Supported by the grants of Palacký University in Olomouc Nr. IGA_LF_2016_038 and IGA_LF_2017_029.

Effect of renal denervation procedure on left ventricular mass, myocardial strain and diastolic function by CMR on a 12-month follow-up.

To investigate the effects of renal denervation (RDN) on left ventricular (LV) mass, myocardial strain and diastolic function in patients with treatment-resistant arterial hypertension by cardiac magnet resonance imaging on a 12-month follow-up. Sixteen patients (38% female) were examined before and 12months after RDN. LV morphology and strain were analyzed. Diastolic function was determined by early (EPFR) and atrial peak filling rates (APFR) derived from differential volume-time-curve analysis. Clinical visits included 24-h ambulant blood pressure monitoring (ABPM). Twelve months after RDN LV mass decreased from 80 ± 21g/m2 to 74 ± 20g/m2 (P < 0.05). Global radial (35 ± 12% vs. 41 ± 10%, P < 0.05) and longitudinal strain improved (-15 ± 4% vs. -17 ± 3%, P < 0.05). Global circumferential strain (-16 ± 5% vs. -18 ± 4%, P = 0.12) remained unchanged. The parameter of diastolic LV function PFRR (EPFR/APFR) improved following RDN (0.9 ± 0.4 vs. 1.1 ± 0.5, P < 0.05). Individual changes of LV mass were associated with an increase of EPFR (r = -0.54, P < 0.05) and a reduction of APFR by trend (r = 0.45, P = 0.08). Systolic ABPM showed a decrease by trend (152mmHg vs. 148mmHg, P = 0.08). After RDN we observed a reduction of LV mass, improvement of global strain and diastolic function.

Stimulation of the baroreceptors for the treatment of resistant arterial hypertension. Clinical trials

Stimulation of the baroreceptors for the treatment of resistant arterial hypertension. Clinical trials

Resistant Hypertension On Treatment (ResHypOT): sequential nephron blockade compared to dual blockade of the renin-angiotensin-aldosterone system plus bisoprolol in the treatment of resistant arterial hypertension \u2013 study protocol for a randomized controlled trial

BackgroundResistant hypertension is characterized when the blood pressure (BP) remains above the recommended goal after taking three antihypertensive drugs with synergistic actions at their maximum recommended tolerated doses, preferably including a diuretic. Identifying the contribution of intravascular volume and serum renin in maintaining BP levels could help tailor more effective hypertension treatment, whether acting on the control of intravascular volume or sodium balance, or acting on the effects of the renin-angiotensin-aldosterone system (RAAS) on the kidney.Methods/designThis is a randomized, open-label, clinical trial is designed to compare sequential nephron blockade and its contribution to the intravascular volume component with dual blockade of the RAAS plus bisoprolol and the importance of serum renin in maintaining BP levels. The trial has two arms: sequential nephron blockade versus dual blockade of the RAAS (with an angiotensin converting enzyme (ACE) inhibitor plus a beta-blocker) both added-on to a thiazide diuretic, a calcium-channel blocker and an angiotensin receptor-1 blocker (ARB). Sequential nephron blockade consists in a progressive increase in sodium depletion using a thiazide diuretic, an aldosterone-receptor blocker, furosemide and, finally, amiloride.On the other hand, the dual blockade of the RAAS consists of the progressive addition of an ACE inhibitor until the maximum dose and then the administration of a beta-blocker until the maximum dose. The primary outcomes will be reductions in the systolic BP, diastolic BP, mean BP and pulse pressure (PP) after 20 weeks of treatment. The secondary outcomes will evaluate treatment safety and tolerability, biochemical changes, evaluation of renal function and recognition of hypotension (ambulatory BP monitoring (ABPM)). The sample size was calculated assuming an alpha error of 5% to reject the null hypothesis with a statistical power of 80% giving a total of 40 individuals per group.DiscussionIn recent years, the cost of resistant hypertension (RH) treatment has increased. Thus, identifying the contribution of intravascular volume and serum renin in maintaining BP levels could help tailor more effective hypertension treatment, whether by acting on the control of intravascular volume or sodium balance, or by acting on the effects of the RAAS on the kidney.Trial registrationSequential Nephron Blockade vs. Dual Blockade Renin-angiotensin System + Bisoprolol in Resistant Arterial Hypertension (ResHypOT). ClinicalTrials.gov, ID: NCT02832973. Registered on 14 July 2016. First received: 12 June 2016. Last updated: 18 July 2016.

Effects of regular physical activity on pain, anxiety, and depression in patients with treatment-resistant arterial hypertension

Effects of regular physical activity on pain, anxiety, and depression in patients with treatment-resistant arterial hypertension

Side effects limit acute efficacy of unilateral unipolar electrical carotid sinus stimulation in patients with treatment resistant arterial hypertension

Side effects limit acute efficacy of unilateral unipolar electrical carotid sinus stimulation in patients with treatment resistant arterial hypertension

Abstract P152: Acute Effect of Unilateral Unipolar Electrical Carotid Sinus Stimulation in Patients with Treatment-Resistant Arterial Hypertension

Electrical carotid sinus stimulation has been developed for treatment of resistant arterial hypertension. The first-generation device (Rheos™) relying on bilateral placement of bipolar electrodes acutely reduced muscle sympathetic nerve activity (MSNA) and blood pressure (BP) but is no longer available. The second-generation device (Neo™) utilizes a smaller unilateral unipolar disk electrode to reduce invasiveness while saving battery life. We tested acute effects of the latter on BP and MSNA. We studied 18 treatment-resistant hypertensive patients (9 women, 53±11 years, 34±5 kg/m 2 ) on stable medication who had been implanted with the second-generation device. We assessed acute BP (oscillometry), heart rate (HR, ECG), and MSNA (microneurography) responses to electrical stimulation in the supine position. Without stimulation, BP was 165±31/91±18 mmHg, HR was 75±17 bpm, and MSNA was 48±14 bursts/min. Acute stimulation with intensities producing side effects that were tolerable in the short term elicited variable changes in systolic BP (SBP: -16.9±15.0 mmHg, range: 0.0 to -40.8 mmHg, p=0.002), HR (-3.6±3.6 bpm, p=0.004), and MSNA (-1.9±5.3 bursts/min, p=0.194). Stimulation intensities had to be lowered in 12 patients to avoid side effects at the expense of efficacy (SBP: -6.3±7.0 mmHg, range: 2.8 to -14.5 mmHg, p=0.028; HR: -1.5±2.3 bpm, p=0.078; comparison against responses with side effects). Reductions in diastolic BP and MSNA (total activity) tended to be correlated (r 2 =0.202, p=0.093). In our patient cohort, unilateral unipolar electrical baroreflex stimulation acutely lowered BP. Side effects may limit efficacy. The novel approach should be tested in a controlled comparative study.

Spike rate of multi-unit muscle sympathetic nerve fibers after catheter-based renal nerve ablation

Patients with treatment-resistant arterial hypertension exhibited profound reductions in single sympathetic vasoconstrictor fiber firing rates after renal nerve ablation. In contrast, integrated multi-unit muscle sympathetic nerve activity (MSNA) changed little or not at all. We hypothesized that conventional MSNA analysis may have missed single fiber discharges, thus, obscuring sympathetic inhibition after renal denervation. We studied patients with difficult-to-control arterial hypertension (age 45–74 years) before, 6 (n = 11), and 12 months (n = 8) after renal nerve ablation. Electrocardiogram, respiration, brachial, and finger arterial blood pressure (BP), as well as the MSNA and raw MSNA signals were analyzed. We detected MSNA action-potential spikes using 2 stage kurtosis wavelet denoising techniques to assess mean, median, and maximum spike rates for each beat-to-beat interval. Supine heart rate and systolic BP did not change at 6 (ΔHR: −2 ± 3 bpm; ΔSBP: 2 ± 9 mm Hg) or at 12 months (ΔHR: −1 ± 3 mm Hg, ΔSBP: −1 ± 9 mm Hg) after renal nerve ablation. Mean burst frequency and mean spike frequency at baseline were 34 ± 3 bursts per minute and 8 ± 1 spikes per second. Both measurements did not change at 6 months (−1.4 ± 3.6 bursts/minute; −0.6 ± 1.4 spikes/second) or at 12 months (−2.5 ± 4.0 bursts/minute; −2.0 ± 1.6 spikes/second) after renal nerve ablation. After renal nerve ablation, BP decreased in 3 of 11 patients. BP and MSNA spike frequency changes were not correlated (slope = −0.06; P = .369). Spike rate analysis of multi-unit MSNA neurograms further suggests that profound sympathetic inhibition is not a consistent finding after renal nerve ablation.

Electrical carotid sinus stimulation: chances and challenges in the management of treatment resistant arterial hypertension.

Treatment resistant arterial hypertension is associated with excess cardiovascular morbidity and mortality. Electrical carotid sinus stimulators engaging baroreflex afferent activity have been developed for such patients. Indeed, baroreflex mechanisms contribute to long-term blood pressure control by governing efferent sympathetic and parasympathetic activity. The first-generation carotid sinus stimulator applying bilateral bipolar stimulation reduced blood pressure in a controlled clinical trial but nevertheless failed to meet the primary efficacy endpoint. The second-generation device utilizes smaller unilateral unipolar electrodes, thus decreasing invasiveness of the implantation while saving battery. An uncontrolled clinical study suggested improvement in blood pressure with the second-generation device. We hope that these findings as well as preliminary observations suggesting cardiovascular and renal organ protection with electrical carotid sinus stimulation will be confirmed in properly controlled clinical trials. Meanwhile, we should find ways to better identify patients who are most likely to benefit from electrical carotid sinus stimulation.

Renal denervation in the treatment of resistant arterial hypertension.

Patients with resistant arterial hypertension have an increased risk of stroke, myocardial infarction, heart failure, and chronic kidney disease. In many cases, limitations of pharmacological treatment like intolerance and adherence to the antihypertensive medications are present in the clinical setting. In this context, new treatment options like trans-femoral sympathetic renal nerve denervation is, even after publication of the Symplicity HTN-3 trial, a promising new treatment option.