Carotid Baroreceptor Stimulation Research Articles

Effects of acute carotid baroreceptor stimulation on sympathetic nerve traffic in resistant and uncontrolled hypertension: a systematic review and meta-analysis.

In resistant hypertensive patients acute carotid baroreflex stimulation is associated with a blood pressure (BP) reduction, believed to be mediated by a central sympathoinhbition.The evidence for this sympathomodulatory effect is limited, however. This meta-analysis is the first to examine the sympathomodulatory effects of acute carotid baroreflex stimulation in drug-resistant and uncontrolled hypertension, based on the results of microneurographic studies. The analysis included 3 studies assessing muscle sympathetic nerve activity (MSNA) and examining 41 resistant uncontrolled hypertensives. The evaluation included assessment of the relationships between MSNA and clinic heart rate and BP changes associated with the procedure. Carotid baroreflex stimulation induced an acute reduction in clinic systolic and diastolic BP which achieved statistical significance for the former variable only [systolic BP: -19.98 mmHg (90% CI, -30.52, -9.43), P < 0.002], [diastolic BP: -5.49 mmHg (90% CI, -11.38, 0.39), P = NS]. These BP changes were accompanied by a significant MSNA reduction [-4.28 bursts/min (90% CI, -8.62, 0.06), P < 0.07], and by a significant heart rate decrease [-3.65 beats/min (90% CI, -5.49, -1.81), P < 0.001]. No significant relationship was detected beween the MSNA, systolic and diastolic BP changes induced by the procedure, this being the case also for heart rate. Our data show that the acute BP lowering responses to carotid baroreflex stimulation, although associated with a significant MSNA reduction, are not quantitatively related to the sympathomoderating effects of the procedure. This may suggest that these BP effects depend only in part on central sympathoinhibition, at least in the acute phase following the intervention.

Advances in the Pathogenesis and Treatment of Resistant Hypertension.

Hypertension is a prevalent chronic disease associated with an increased risk of cardiovascular (CV) premature death, and its severe form manifests as resistant hypertension (RH). The accurate prevalence of resistant hypertension is difficult to determine due to the discrepancy in data from various populations, but according to recent publications, it ranges from 6% to 18% in hypertensive patients. However, a comprehensive understanding of the pathogenesis and treatment of RH is essential. This review emphasizes the importance of identifying the causes of treatment resistance in antihypertensive therapy and highlights the utilization of appropriate diagnostic methods. We discussed innovative therapies such as autonomic neuromodulation techniques like renal denervation (RDN) and carotid baroreceptor stimulation, along with invasive interventions such as arteriovenous anastomosis as potential approaches to support patients with inadequate medical treatment and enhance outcomes in RH.

EFFECTS OF CAROTID BARORECEPTOR STIMULATION ON REGIONAL SYMPATHETIC ACTIVITY IN CHRONIC HEART FAILURE

Objective: Carotid baroreceptor stimulation (BAT) exerts in heart failure (CHF) sympatho-inhibitory effects. No information is available, however, on whether these effects have a regional or a more generalized behaviour. Design and method: In 9 CHF patients (age 58.3 ± 252 yrs, mean ± SD) we recorded via the microneurographic technique muscle and skin sympathetic nerve traffic (MSNA and SSNA, respectively) before, 6 and 12 months following BAT. Measurements included left ventricular ejection fraction (LVEF), brain natriuretic peptide BNP (elisa), 6-minute walking test (6WT), New York Heart Association (NYHA) class, Minnesota score, together with routine laboratory variables. 10 age-matched CHF patients not underwent BAT served as controls. Results: BAT caused significant increase in LVEF (from 33.4 ± 5.1 to 37.1 ± 5.4%, P &lt; 0.05) and in 6 WT, and a significant reduction in the Minnesota score and in NYHA class (from 3.3 ± 0.4 to 2.4 ± 0.4 a.u), unaltering BNP. MSNA, but not SSNA, was markedky activated in CHF. BAT caused a significant reduction in MSNA 6 and 12 months follow-up (from 70.7 ± 2.7 to 47.0 ± 4.3 and 44.1 ± 3.5 bursts/100heartbeats, means ± SD, P &lt; 0.05). This effect was not accompanied by any significant change in SSNA (from 11.3 ± 2.1 to 11.5 ± 1.7 and 11.6 ± 2.1 bursts/minute, P = NS). A significant correlation was found between baseline MSNA values and the MSNA changes after BAT, which were also related to the LVEF modifications. No significant change in the various variables was detected in the control group followed for a 12 month observation. Conclusions: These data provide the first evidence that BAT exerts heterogeneous effects on sympathetic cardiovascular drive, inducing a marked reduction in MSNA but not in SSNA, which appears to be within the normal range in this condition. These effects may depend on the different reflex modulation regulating neuroadrenergic drive in these cardiovascular districts.

Carotid baroreceptor stimulation prevents oxidative stress by inhibiting MAO-A and prevents cardiac remodeling in obese rats.

Sympathetic nervous system overactivation and abnormal lipid metabolism are featured in obesity and may lead to cardiac remodeling. The effects of carotid baroreceptor stimulation (CBS) on cardiac remodeling in obese rats and the underlying mechanisms were explored. An obesity model was induced by 16-week high-fat diet feeding. A CBS device was implanted at the 8th week. Body weight and blood pressure measurements, electrocardiography, echocardiography, and glucose and insulin tolerance tests were conducted before sampling. Plasma analysis and histological and biological analyses of left ventricle were also performed. Neonatal rat cardiomyocytes cocultured with 3T3-L1 in transwell chambers were used to investigate the mechanisms. CBS alleviated several manifestations of obesity, including increased body weight, high blood pressure, hyperlipidemia, and enhanced sympathetic activity. In obese hearts, norepinephrine levels decreased, and the monoamine oxidase A (MAO-A) and reactive oxygen species level increased; these changes, as well as cardiac fibrosis, lipid metabolic disorders, and heart dysfunction, were inhibited by CBS. Neonatal rat cardiomyocytes incubated with norepinephrine showed MAO-A upregulation, increased reactive oxygen species levels, lipid metabolic disorders, and inflammatory response, which were inhibited by clorgyline, a selective MAO-A inhibitor. CBS effectively suppresses sympathetic nervous system activity and oxidative stress mediated by MAO-A and prevents cardiac remodeling in obese rats.

Low intensity stimulation of aortic baroreceptor afferent fibers as a potential therapeutic alternative for hypertension treatment

Carotid baroreceptor stimulation has been clinically explored for antihypertensive benefits, but neuromodulation of aortic baroreceptor afferents remains unexplored for potential translation into the clinic. Published studies have used supramaximal stimulations, which are unphysiological and energy inefficient. The objective of the present study was to identify optimal low-charge nerve stimulation parameters that would provide a clinically-relevant (20–30 mmHg) decrease in mean arterial pressure (MAP) in anesthetized spontaneously hypertensive rats. Stimulations of 20 s were delivered to the left aortic depressor nerve (ADN) of these rats using low ranges of pulse amplitudes (≤ 0.6 mA), widths (≤ 0.5 ms) and frequencies (≤ 5 Hz). We also assessed the effects of continuous (20 s) versus intermittent (5 s ON/3 s OFF and 5 s ON/3 s OFF for 20 s) stimulation on MAP, heart rate (HR), mesenteric (MVR) and femoral (FVR) vascular resistance using low (5 Hz) and high (15 Hz) frequencies. Lower pulse amplitudes (0.2 mA) produced 9 ± 2 to 18 ± 2 mmHg decreases in MAP. Higher pulse amplitudes (0.4 mA) produced a median MAP reduction of 28 ± 4 mmHg at 0.2 ms and 5 Hz, with no added benefit seen above 0.4 mA. Continuous and intermittent low frequency stimulation at 0.4 mA and 0.2 ms produced similar sustained decreases in MAP, HR, MVR and FVR. Continuous high frequency stimulation at 0.4 mA and 0.2 ms produced larger reductions in MAP, HR, MVR and FVR compared with all low frequency and/or intermittent high frequency stimulations. We conclude from these findings that “low intensity intermittent” electrical stimulation is an effective alternate way for neuromodulation of the aortic baroreceptor afferents and to evoke a required restoration of MAP levels in spontaneously hypertensive rats. This approach enables low energy consumption and markedly lowers the excessive decreases in MAP and hemodynamic disturbances elicited by continuous high-charge injection protocols.

Interventional Therapy in Refractory Hypertension: An Update

Abstract Hypertension represents a major public health issue, affecting about 26% of the world's population. It is the most common cardiovascular risk factor worldwide, with a prevalence that continues to grow. Among this hypertensive population, a critical subgroup is that of patients with resistant hypertension. For subjects with truly resistant hypertension, the next step after nonpharmacological interventions and drug therapy is represented by interventional treatment. However, implementing an interventional approach in resistant hypertension represents a real challenge. The decision needs to be undertaken in multidisciplinary teams, which must include a specialist in hypertension, and it is not routinely recommended. The main device-based therapies for hypertension are represented by carotid baroreceptor stimulation, renal denervation, and the creation of an arteriovenous fistula. Until 2018, there was an important controversy on the beneficial effects of renal sympathetic denervation. One cannot ignore, however, the positive results of interventional therapy for treatment-resistant hypertension obtained in different trials conducted on a large number of patients. A significant reduction in blood pressure values and an improvement in cardiovascular outcomes could be attained with interventional therapy through a rigorous selection of patients.

Transient effects of carotid baroreflex stimulation via the neck chamber device on central venous pressure.

We examined in 11 young subjects (age 29.7±3.6 years, mean±SEM) whether carotid baroreceptor stimulation via the neck chamber device may affect central venous pressure (CVP), thus potentially involving other reflexogenic areas in the examined responses. Application of progressively greater neck chamber subatmospheric pressures caused a progressive lengthening in RR interval, which reached a peak at the maximal value of negative neck chamber pressure applied. This was accompanied by significant and progressively greater reduction in CVP values when the data were calculated considering the early changes occurring within the first 2 seconds of the stimulus. There was a weak correlation between the early changes in CVP and the RR interval responses when all stimuli were pooled together (r = 0.32, P < .05). The results of the present study suggest that the neck chamber technique employed to assess carotid baroreceptor‐heart rate sensitivity can transiently affect via the CVP reduction cardiopulmonary receptors activity, which may participate at the integrated reflex responses.

The Sympathetic Nervous System in Hypertension: Roadmap Update of a Long Journey.

The present paper will provide an update on the role of sympathetic neural factors in the development and progression of essential hypertension by reviewing data collected in the past 10 years. This will be done by discussing the results of the published studies in which sympathetic neural function in essential hypertension and related disease has been investigated via sophisticated and highly sensitive techniques, such as microneurographic recording of sympathetic nerve traffic and regional norepinephrine spillover. First, the relevance of the pathophysiological background of the neurogenic alterations will be discussed. It will be then examined the behavior of the sympathetic neural function in specific clinical phenotypes, such as resistant hypertension, pseudoresistant hypertension, and hypertensive states displaying elevated resting heart values. This will be followed by a discussion of the main results of the meta-analytic studies examining the behavior of sympathetic nerve traffic in essential hypertension, obesity, metabolic syndrome, and chronic renal failure. The sympathetic effects of renal denervation and carotid baroreceptor stimulation as well as the possible involvement of sympathetic neural factors in the determination of the so-called “residual risk” of the treated hypertensive patients will be finally discussed.

Evolving Cardiac Electrical Therapies for Advanced Heart Failure Patients.

Symptomatic heart failure (HF) patients despite optimal medical therapy and advances such as invasive hemodynamic monitoring remain challenging to manage. While cardiac resynchronization therapy remains a highly effective therapy for a subset of HF patients with wide QRS, a majority of symptomatic HF patients are poor candidates for such. Recently, cardiac contractility modulation, neuromodulation based on carotid baroreceptor stimulation, and phrenic nerve stimulation have been approved by the US Food and Drug Administration and are emerging as therapeutic options for symptomatic HF patients. This state-of-the-art review examines the role of these evolving electrical therapies in advanced HF.

Effects of carotid baroreceptor stimulation on aortic remodeling in obese rats

Background and aimOur previous study found carotid baroreceptor stimulation (CBS) reduces body weight and white adipose tissue (WAT) weight, restores abnormal secretion of adipocytokines and inflammation factors, decreases systolic blood pressure (SBP) by inhibiting activation of sympathetic nervous system (SNS) and renin-angiotensin system (RAS) in obese rats. In this study, we explore effects of CBS on aortic remodeling in obese rats. Methods and resultsRats were fed high-fat diet (HFD) for 16 weeks to induce obesity and underwent either CBS device implantation and stimulation or sham operation at 8 weeks. BP and body weight were measured weekly. RAS activity of WAT, histological, biochemical and functional profiles of aortas were detected after 16 weeks. CBS effectively decreased BP in obese rats, downregulated mRNA expression of angiotensinogen (AGT) and renin in WAT, concentrations of AGT, renin, angiotensin II (Ang II), protein levels of Ang II receptor 1 (AT1R) and Ang II receptor 2 (AT2R) in WAT were declined. CBS inhibited reactive oxygen species (ROS) generation, inflammatory response and endoplasmic reticulum (ER) stress in aortas of obese rats, restrained vascular wall thickening and vascular smooth muscle cells (VSMCs) phenotypic switching, increased nitric oxide (NO) synthesis, promoted endothelium-dependent vasodilatation by decreasing protein expression of AT1R and leptin receptor (LepR), increasing protein expression of adiponectin receptor 1 (AdipoR1) in aortic VSMCs. ConclusionCBS reduced BP and reversed aortic remodeling in obese rats, the underlying mechanism might be related to the suppressed SNS activity, restored adipocytokine secretion and restrained RAS activity of WAT.

Sympathomodulation in congestive heart failure: From drugs to devices

Indirect and direct approaches to assess sympathetic neural function in man have shown that congestive heart failure is characterized by a marked adrenergic overdrive. Although compensatory in the initial phases of the disease, with time the sympathetic overactivity exerts adverse cardiovascular effects, favoring the disease progression and promoting the occurrence of non-fatal and fatal cardiovascular events. This explains why the adrenergic overactivity has become an important target of the therapeutic interventions adopted in the managementof the disease. The present paper will examine the impact of therapeutic approaches, used in the management of heart failure, on the sympathetic activation characterizing the disease. After a brief mention of the sympathetic effects of non-pharmacological interventions and procedural approches, particular emphasis will be given to the effects of pharmacological interventions and device treatments (renal denervation and carotid baroreceptor stimulation), which became in recent years a promising tool for the management of the disease. The clinical implications as well as the unsolved aspects related to the sympathomodulatory interventions in heart failure management will be finally discussed.

Sympathetic activation in congestive heart failure: an updated overview.

Conclusive evidence demonstrates that the sympathetic nervous system activation is a hallmark of congestive heart failure. This has been shown via a variety of biochemical, neurophysiological, and neuroimaging approaches for studying human sympathetic neural function. The sympathetic activation appears to be an early phenomenon in the clinical course of the disease, closely related to its severity and potentiated by the concomitant presence of other comorbidities, such as obesity, diabetes mellitus, metabolic syndrome, hypertension, and renal failure. The adrenergic overdrive in heart failure is associated with other sympathetic abnormalities, such as the downregulation of beta-adrenergic adrenoreceptors at cardiac level, and exerts unfavorable consequences on the cardiovascular system. These include the endothelial dysfunction, the development of left ventricular hypertrophy, the atherosclerosis development, as well as the generation of atrial and ventricular arrhythmias, and, at very extreme levels of sympathetic activation, the occurrence of microscopic myocardial necrosis. Given the close direct independent relationships detected in heart failure between sympathetic activation and mortality, the adrenergic overdrive has become a target of neuromodulatory therapeutic interventions, which include non-pharmacological, pharmacological, and device-based interventions. For some of these approaches (specifically bilateral renal nerves ablation and carotid baroreceptor stimulation), additional studies are needed to better define their impact on the clinical course of the disease.

Carotid baroreceptor stimulation in obese rats affects white and brown adipose tissues differently in metabolic protection

The sympathetic nervous system (SNS) regulates the functions of white adipose tissue (WAT) and brown adipose tissue (BAT) tightly. Carotid baroreceptor stimulation (CBS) efficiently inhibits SNS activation. We hypothesized that CBS would protect against obesity. We administered CBS to obese rats and measured sympathetic and AMP-activated protein kinase (AMPK)/ PPAR pathway responses as well as changes in perirenal WAT (PWAT), epididymal WAT (EWAT), and interscapular BAT (IBAT). CBS alleviated obesity-related metabolic changes, improving insulin resistance; reducing adipocyte hypertrophy, body weight, and adipose tissue weights; and decreasing norepinephrine but increasing acetylcholine in plasma, PWAT, EWAT, and IBAT. CBS also downregulated fatty acid translocase (CD36), fatty acid transport protein (FATP), phosphorylated and total hormone sensitive lipase, phosphorylated and total protein kinase A, and PPARγ in obese rats. Simultaneously, CBS upregulated phosphorylated adipose triglyceride lipase, phosphorylated and total AMPK, and PPARα in PWAT, EWAT, and IBAT. However, BAT and WAT responses differed; although many responses were more sensitive in IBAT, responses of CD36, FATP, and PPARγ were more sensitive in PWAT and EWAT. Overall, CBS decreased chronically activated SNS and ameliorated obesity-related metabolic disorders by regulating the AMPK/PPARα/γ pathway.

Carotid baroreceptor stimulation improves cardiac performance and reverses ventricular remodelling in canines with pacing-induced heart failure

AimsCarotid baroreceptor stimulation (CBS) has potential protective effects on chronic heart failure (CHF). The aim of our study was to investigate the effects of CBS on more detailed aspects of ventricular remodelling and the underlying mechanisms in a CHF canine model. Main methodsTwenty-four beagles were randomised into Con (n = 8), CHF (n = 8), and CHF-CBS (n = 8) groups. The CHF and CHF-CBS groups underwent 6 weeks of rapid ventricular pacing (RVP) at 250 beats per minute to establish a CHF model. Concomitant CBS was delivered together with RVP in the CHF-CBS group. Key findingsRVP for 6 weeks caused typical heart failure in the CHF group. CBS significantly reversed the decrease in the high-frequency heart rate variability component and increase in low-frequency/high-frequency ratio induced by RVP. CBS significantly reduced cardiac dilation, improved left ventricle ejection fraction, and inhibited the increase in natriuretic peptide mRNA expression of LV tissue. CBS alleviated collagen volume fraction and reduced protein expression of transforming growth factor β1, matrix metallopeptidase 2, and matrix metallopeptidase 9, as well as decreased the percentage of TUNEL-positive nuclei and protein expression of Caspase-3 in LV tissue. The intracellular PKA signalling pathway and cardiac inflammation of LV tissue were upregulated in the CHF group, and markedly inhibited by CBS. SignificanceOur study found that CBS improved cardiac performance and reversed ventricular remodelling in CHF canines by rebalancing the autonomic nervous system; the suppression of the intracellular PKA signalling pathway and cardiac inflammation might underly the mechanisms.

2018 ESC/ESH guidelines about new methods of treatment of hypertension — “DEVICE-BASED TREATMENT”

Arterial hypertension (HTN) needs new treatment methods, including invasive ones, because HTN has severe consequences and involves all regulating systems (neuro-cardio-renal/cerebral continuum). It is often associated with comorbid pathology (obesity, atherosclerosis, sleep disorder, diabetes mellitus, etc.). The paper presents a summary of the position of the European experts on some invasive methods of HTN treatment — “DEVICE-BASED TREATMENT” (DBT) in the section of new recommendations of the European Societies of Cardiology/Hypertension (2018 ESC/ESH Guidelines for the management of arterial hypertension), including carotid baroreceptor stimulation, renal denervation, arteriovenous fistula formation and other. The experts do not recommend to use DBT in routine practice, confirm high requirement and demand of clinical and basic investigations to prove their safety and efficiency.

Clinical Value of Measuring the Renin/Aldosterone Levels: Optimising the Management of Uncontrolled/Resistant Hypertension.

Resistant hypertension (HT) is a common clinical entity with debilitating cardiovascular consequences. The highly heterogeneous nature of resistant HT requires a meticulous workup to exclude 'pseudo-resistance' and secondary forms of arterial HT. Resistant HT has recently gained wide scientific interest due to the introduction of interventional methods (renal sympathetic denervation and carotid baroreceptor stimulation) for blood pressure (BP) reduction in this patient population. Despite however the recent advances in understanding the pathophysiology and the clinical characteristics of the disease, the appropriate management of resistant HT remains elusive. The marked heterogeneity of BP response to interventional therapy underlines the need for careful patient selection and the identification of ideal candidates for interventional therapy. The renin-angiotensin-aldosterone system seems to play a cardinal role in the pathophysiology of resistant HT and requires appropriate management. Furthermore, primary aldosteronism is considered the most common form of secondary HT, with increased prevalence in patients with resistant HT. This review aims to provide a simplified work-up for patients with resistant HT, summarize the rationale for the determination of renin and aldosterone levels, and critically discuss available evidence on when and how to measure renin/aldosterone in resistant HT.

Abstract P110: Low Intensity Stimulation of Aortic Baroreceptors as a Potential Therapeutic Alternative for Hypertension Treatment

Carotid baroreceptor stimulation has been clinically explored for antihypertensive benefits but aortic baroreceptor modulation remains untouched for clinical translation. Published studies use large current/voltage amplitudes (10V), longer pulse widths (2 ms) or ultra-high frequencies (70-100 Hz). These are energy inefficient neuromodulation methods. Our main goal was to identity optimal nerve stimulation parameters that would provide a sustained drop in mean arterial pressure (MAP) of ~30 mmHg. We stimulated aortic depressor nerve (ADN) in spontaneously hypertensive rats (SHR, n =4) at low ranges of frequencies, pulse amplitudes and pulse widths. Under urethane anesthesia, left ADN was stimulated for 20 seconds at varying frequencies (1, 2.5 and 5 Hz) and pulse amplitudes (0.2, 0.4 and 0.6 mA) at 0.1, 0.2 or 0.5 ms pulse width. A frequency-dependent depressor response was seen at all pulse amplitudes and widths used. Lower pulse amplitudes (0.2 mA) produced ~18 mmHg MAP drop at all pulse widths tested. Higher pulse amplitude (0.4 and 0.6 mA) produced similar drop in MAP of ~34 mmHg. The return to baseline values was relatively prolonged with higher charge injection with 32 seconds at 0.2 mA (0.1 or 0.2 ms at 5 Hz, maximum effect size: -18 mmHg) versus 42 seconds at 0.4 or 0.6 mA (0.1, 0.2 or 0.5 ms at 5 Hz, maximum effect size: -34 mmHg). There was no added benefit of pulse amplitudes beyond 0.4 mA. We conclude that low intensity stimulation is an effective alternate way to neuromodulation of the ADN. This will enable low energy consumption for neuromodulation. Future studies will study impact of these parameters in conscious SHR rats.

Fear processing is differentially affected by lateralized stimulation of carotid baroreceptors

Information processing, particularly of salient emotional stimuli, is influenced by cardiovascular afferent signals. Carotid baroreceptors signal the state of cardiovascular arousal to the brain, controlling blood pressure and heart rate via the baroreflex. Animal studies suggest a lateralization of this effect: Experimental stimulation of the right carotid sinus has a greater impact on heart rate when compared to left-sided stimulation. We tested, in humans, whether the processing of emotional information from faces was differentially affected by right versus left carotid afferents. To achieve so, we used an automated neck suction device to stimulate the carotid mechanoreceptors in the carotid sinus (parasympathetic pathway) synchronously with functional magnetic resonance imaging (fMRI) acquisition whilst participants were engaged in an emotional rating task of fearful and neutral faces. We showed that both right and left carotid stimulation (CS) influenced brain activity within opercular regions, although a stronger activation was observed within left insula during right stimulation compared to left stimulation. As regards the processing of fearful faces, right, but not left carotid stimulation attenuated the perceived intensity of fear, and (albeit to a lesser extent) enhanced intensity ratings of neutral faces. Mirroring the behavioural effects, there was a significant expression-by-stimulation interaction for right carotid stimulation only, when bilateral amygdala responses were attenuated to fear faces and amplified to neutral faces. Individual differences in basal heart rate variability (HRV) predicted the extent to which right carotid stimulation attenuated amygdala responses during fear processing. Our study provides unique evidence for lateralized viscerosensory effects on brain systems supporting emotional processing.

Effects of carotid baroreceptor stimulation on retinal arteriole remodeling evaluated with adaptive optics camera in resistant hypertensive patients

Background and aimBaroreceptor activation therapy (BAT) leads to a decrease in blood pressure (BP) in patients affected by resistant hypertension (RH) by reducing sympathetic outflow. This study aimed at evaluating the effects of BAT on RH patients’ retinal arteriolar microvasculature, a territory devoid of adrenergic innervation. Patients and methodsFive patients defined as affected by RH after excluding secondary causes of hypertension and based on number of antihypertensive treatments, underwent the implantation of Barostim™ neo™. Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) were assessed by office and 24-hours ambulatory BP monitoring (ABPM). Adaptive Optics Camera RTX1® (ImagineEye, Orsay, France) was used to measure wall thickness (WT), internal diameter (ID), wall cross-sectional area (WCSA) and wall-to-lumen ratio (WLR). A cohort of 21 not-controlled hypertensive patients matched for age, gender and follow-up time, undergoing standard-antihypertensive therapy changes, was selected as a control group. SBP and DBP were assessed by office and home BP monitoring (HBPM). Evaluations were performed at baseline and after 6 months mean follow-up. ResultsOffice SBP decreased by 9.7±12.3% and 29.7±12.4% in standard-therapy and BAT group respectively, while office DBP decreased by 7.6±17.4% and 14.8±15.7%. Concerning ABPM/HBPM, a mean reduction of both SBP and DBP of 7.9±11% was observed for the standard-therapy while a reduction of 15.8±10.5% and 15.8%±5.3% was observed for SBP and DBP respectively in BAT group. While in the standard-therapy group a significant reduction in WLR (–5.9%) due to both ID increase (+2.3%) and WT reduction (–5.7%) was observed, without changes in WCSA (–0.3%), RH patients had a significant reduction in WCSA (–12.1%), due to a trend in both WT and ID reduction (–6.5% and –1.7% respectively), without significant changes in WLR (–2%). ConclusionWhile a reverse eutrophic remodeling was observed in patients undergoing a standard-antihypertensive treatment, hypotrophic changes were found in RH patients undergoing BAT. Despite the lack of adrenergic receptors on retinal vessels, chronic baroreflex stimulation may exert an effect on retinal microvasculature in RH patients by more systemic than local mechanisms.

VP101 Medical Devices For Treatment-resistant Hypertension: Health Technology Assessment Report

INTRODUCTION:While optimal medical therapy (OMT) represents the current standard of care for treatment-resistant hypertension, non-pharmaceutical therapeutic approaches, such as renal denervation and carotid baroreceptor stimulation therapy, have been proposed. The present Health Technology Assessment (HTA) project was aimed at assessing benefits and risk of those approaches versus OMT.METHODS:A systematic review of evidence on effectiveness and safety was performed together with a review of economic studies. A contextual analysis of market availability and use of the technology in Italy was also performed.RESULTS:In Italy, ninety-nine renal denervation procedures were performed in 2014. Ten studies from six trials were included in the review and meta-analysis. No evidence of dominance or increased harms of renal denervation compared to OMT were found. Four economic evaluations were included and reported dominance of renal denervation. These were based on short-term clinical data and three evaluations used the same Markov model assuming dominance of renal denervation. Estimated average prospective cost of the procedure was EUR6,129.90 (range EUR3,821.15 – EUR9,714.23). We updated the results of an earlier assessment published by an Italian Regional agency on carotid baroreceptor stimulation therapy (1). None of the three studies identified as ongoing in 2015 were completed or had published preliminary results and the technology was not assessed further within the present HTA project.CONCLUSIONS:Even if follow-up was limited to 6 months, randomised evidence showed no benefits of the procedure. Economic evaluations were unreliable, based on unrealistic assumptions of effectiveness and contrived therapy regimes. Further investment in renal denervation should await the results of well-designed and adequately followed-up trials assessing the impact of renal denervation on major cardiovascular events compared to OMT. Future economic evaluations should be based on realistic assumptions of cost and effectiveness.