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Baroreflex activation: from mechanisms to therapy for cardiovascular disease.

ABSTRACT: Recent technical advances have led to the development of a medical device that can reliably activate the carotid baroreflex with an acceptable degree of safety. Because activation of the sympathetic nervous system plays an important role in the pathogenesis of hypertension and heart failure, the unique ability of this device to chronically suppress central sympathetic outflow in a controlled manner suggests potential value in the treatment of these conditions. This notion is supported by both clinical and experimental animal studies, and the major aim of this article is to elucidate the physiological mechanisms that account for the favorable effects of baroreflex activation therapy in patients with resistant hypertension and heart failure. Illumination of the neurohormonal, renal, and cardiac actions of baroreflex activation is likely to provide the means for better identification of those patients that are most likely to respond favorably to this device-based therapy.

SUBMITTER: Iliescu R

PROVIDER: S-EPMC4364442 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Baroreflex activation: from mechanisms to therapy for cardiovascular disease.

Iliescu Radu R Tudorancea Ionut I Lohmeier Thomas E TE

Current hypertension reports 20140801 8

Recent technical advances have led to the development of a medical device that can reliably activate the carotid baroreflex with an acceptable degree of safety. Because activation of the sympathetic nervous system plays an important role in the pathogenesis of hypertension and heart failure, the unique ability of this device to chronically suppress central sympathetic outflow in a controlled manner suggests potential value in the treatment of these conditions. This notion is supported by both cl ...[more]

PMID: 24899538

Similar Datasets

Chronic lowering of blood pressure by carotid baroreflex activation: mechanisms and potential for hypertension therapy.

Project description:Recent technical advances have renewed interest in device-based therapy for the treatment of drug-resistant hypertension. Findings from recent clinical trials regarding the efficacy of electric stimulation of the carotid sinus for the treatment of resistant hypertension are reviewed here. The main goal of this article, however, is to summarize the preclinical studies that have provided insight into the mechanisms that account for the chronic blood pressure-lowering effects of carotid baroreflex activation. Some of the mechanisms identified were predictable and confirmed by experimentation. Others have been surprising and controversial, and resolution will require further investigation. Although feasibility studies have been promising, firm conclusions regarding the value of this device-based therapy for the treatment of resistant hypertension awaits the results of current multicenter trials.

| S-EPMC3085950 | biostudies-literature

Twiddler's syndrome after implantation of baroreflex activation therapy: a case report.

Project description:BackgroundTwiddler's syndrome is a rare complication after implantation of cardiac pacemakers or cardioverter-defibrillators that usually occurs within the first year after the procedure. However, it has not yet been described following implantation of baroreflex activation therapy (BAT).Case summaryA 61-year-old female patient was referred to the cardiology outpatient clinic due to uncontrolled arterial hypertension despite maximal doses of several established drugs. Therefore, right-sided BAT implantation was successfully performed in February 2017 with good clinical response. Because of sustained neck pain at the site of stimulator, surgical revision was performed in November 2019 including a switch of the lead to the contralateral position. Approximately 1 month later, Twiddler's syndrome was identified on the basis of recurrent pain at the generator site necessitating pocket-revision, however, the lead was only untwisted but not replaced. A few weeks afterwards, unfortunately, lead revision was indispensable due to lead fracture.DiscussionThis case presents the uncommon phenomenon of Twiddler's syndrome after BAT implantation. In addition, the commonly twisted lead should always be replaced as well during surgical pocket-revision in order to ensure proper long-term function.

| S-EPMC8189308 | biostudies-literature

Baroreflex activation therapy in advanced heart failure therapy: insights from a real-world scenario.

Project description:AimsBaroreflex activation therapy (BAT) is an innovative treatment option for advanced heart failure (HFrEF). We analysed patients' BAT acceptance and the outcome of BAT patients compared with HFrEF patients solely treated with a guideline-directed medical therapy (GDMT) and studied effects of sacubitril/valsartan (ARNI).MethodsIn this prospective study, 40 HFrEF patients (71 ± 3 years, 20% female) answered a questionnaire on the acceptance of BAT. Follow-up visits were performed after 3, 6, and 12 months. Primary efficacy endpoints included an improvement in QoL, NYHA class, LVEF, HF hospitalization, NT-proBNP levels, and 6MHWD.ResultsTwenty-nine patients (73%) showed interest in BAT. Ten patients (25%) opted for implantation. BAT and BAT + ARNI patients developed an increase in LVEF (BAT +10%, P-value (P) = 0.005*; BAT + ARNI +9%, P = 0.049*), an improved NYHA class (BAT -88%, P = 0.014*, BAT + ARNI -90%, P = 0.037*), QoL (BAT +21%, P = 0.020*, BAT + ARNI +22%, P = 0.012*), and reduced NT-proBNP levels (BAT -24%, P = 0.297, BAT + ARNI -37%, P = 0.297). BAT HF hospitalization rates were lower (50%) compared with control group patients (83%) (P = 0.020*).ConclusionsAlthough BAT has generated considerable interest, acceptance appears to be ambivalent. BAT improves outcome with regard to LVEF, NYHA class, QoL, NT-proBNP levels, and HF hospitalization rates. BAT + ARNI resulted in more pronounced effects than ARNI alone.

| S-EPMC9871720 | biostudies-literature

Kidney protective effects of baroreflex activation therapy in patients with resistant hypertension.

Project description:Baroreflex activation therapy (BAT) is approved for the treatment of resistant hypertension. In addition to blood pressure (BP) reduction, pilot studies suggested several organoprotective effects of BAT. Thirty-two patients with resistant hypertension were prospectively treated with BAT. Besides office BP and 24-hour ambulatory BP (ABP) measurements, detection of a urinary proteome-based classifier (CKD273), which has been shown to predict chronic kidney disease (CKD) progression, was carried out at baseline and after 6 months of BAT. Office BP significantly decreased from 170 ± 25/90 ± 18 to 149 ± 29/82 ± 18 mm Hg. Analysis of CKD273 score and eGFR with CKD-EPI equation at baseline revealed strong correlation (r = 0.568, P < 0.001). After 6 months of BAT, there was no significant change in CKD273 score (-0.061 [95% CI: -0.262 to 0.140], P = 0.601). However, by stratification of the data regarding ABP response, there was a statistically significant (P = 0.0113) reduction in the CKD273 score from a mean of 0.161 [95% CI: -0.093 to 0.414] to -0.346 [95% CI: -0.632 to -0.060] after BAT in patients with systolic ABP decrease of ≥5 mm Hg. These data emphasized potential nephroprotective effects of BAT in patients with sufficient BP response.

| S-EPMC8030795 | biostudies-literature

Mineralocorticoid receptor activation and antagonism in cardiovascular disease: cellular and molecular mechanisms.

Project description:Aldosterone controls salt-water homeostasis by acting on the mineralocorticoid receptor (MR), a ligand-activated transcription factor, in kidney epithelial cells. However, it is now evident that the MR is expressed in multiple cell types and tissues, acting as a key driver of cardiovascular disease. MR antagonists have proven to be highly efficient in patients with heart failure and reduced ejection fraction, and they are a cornerstone of contemporary therapy. In the past decade, a series of experimental studies using models with cell type-specific MRs uncovered the cellular and molecular mechanisms underlying its detrimental effect on left ventricular remodeling. Based on these findings, the potential of MR antagonists has been evaluated in other cardiovascular diseases, including coronary artery disease, arterial hypertension, heart failure with preserved ejection fraction, pulmonary hypertension, atrial fibrillation, and heart valve disease. The present review summarizes the current knowledge on MR activation and antagonism in cardiovascular disease.

| S-EPMC9073241 | biostudies-literature

In silico trial of baroreflex activation therapy for the treatment of obesity-induced hypertension.

Project description:Clinical trials evaluating the efficacy of chronic electrical stimulation of the carotid baroreflex for the treatment of hypertension (HTN) are ongoing. However, the mechanisms by which this device lowers blood pressure (BP) are unclear, and it is uncertain which patients are most likely to receive clinical benefit. Mathematical modeling provides the ability to analyze complicated interrelated effects across multiple physiological systems. Our current model HumMod is a large physiological simulator that has been used previously to investigate mechanisms responsible for BP lowering during baroreflex activation therapy (BAT). First, we used HumMod to create a virtual population in which model parameters (n = 335) were randomly varied, resulting in unique models (n = 6092) that we define as a virtual population. This population was calibrated using data from hypertensive obese dogs (n = 6) subjected to BAT. The resultant calibrated virtual population (n = 60) was based on tuning model parameters to match the experimental population in 3 key variables: BP, glomerular filtration rate, and plasma renin activity, both before and after BAT. In the calibrated population, responses of these 3 key variables to chronic BAT were statistically similar to experimental findings. Moreover, blocking suppression of renal sympathetic nerve activity (RSNA) and/or increased secretion of atrial natriuretic peptide (ANP) during BAT markedly blunted the antihypertensive response in the virtual population. These data suggest that in obesity-mediated HTN, RSNA and ANP responses are key factors that contribute to BP lowering during BAT. This modeling approach may be of value in predicting BAT responses in future clinical studies.

| S-EPMC8601446 | biostudies-literature

Response by Sex in Patient-Centered Outcomes With Baroreflex Activation Therapy in Systolic Heart Failure.

Project description:ObjectivesThe aim of this study was to assess sex differences in the efficacy and safety of baroreflex activation therapy (BAT) in the BeAT-HF (Baroreflex Activation Therapy for Heart Failure) trial.BackgroundPatients were randomized 1:1 to receive guideline-directed medical therapy (GDMT) alone (control group) or BAT plus GDMT.MethodsPre-specified subgroup analyses including change from baseline to 6 months in 6-min walk distance (6MWD), quality of life (QoL) assessed using the Minnesota Living With Heart Failure Questionnaire (MLWHQ), New York Heart Association (NYHA) functional class, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were conducted in men versus women.ResultsFifty-three women and 211 men were evaluated. Women had similar baseline NT-proBNP levels, 6MWDs, and percentage of subjects with NYHA functional class III symptoms but poorer MLWHQ scores (mean 62 ± 22 vs. 50 ± 24; p = 0.01) compared with men. Women experienced significant improvement from baseline to 6 months with BAT plus GDMT relative to GDMT alone in MLWHQ score (-34 ± 27 vs. -9 ± 23, respectively; p < 0.01), 6MWD (44 ± 45 m vs. -32 ± 118 m; p < 0.01), and improvement in NYHA functional class (70% vs. 27%; p < 0.01), similar to the responses seen in men, with no significant difference in safety. Women receiving BAT plus GDMT had a significant decrease in NT-proBNP (-43% vs. 7% with GDMT alone; difference -48%; p < 0.01), while in men this decrease was -15% versus 2%, respectively (difference -17%; p = 0.08), with an interaction p value of 0.05.ConclusionsWomen in BeAT-HF had poorer baseline QoL than men but demonstrated similar improvements with BAT in 6MWD, QoL, and NYHA functional class. Women had a significant improvement in NT-proBNP, whereas men did not. (Baroreflex Activation Therapy for Heart Failure [BeAT-HF]; NCT02627196).

| S-EPMC8852222 | biostudies-literature

Cardiopulmonary function during exercise in heart failure with reduced ejection fraction following baroreflex activation therapy.

Project description:PurposeBaroreflex activation therapy has favorable effects in heart failure patients. We report the results of a single-center study of baroreflex activation therapy in heart failure with reduced ejection fraction including cardiopulmonary exercise testing for the first time to show the effect on exercise capacity.MethodsA total of 17 patients were treated with baroreflex activation therapy. Eligibility criteria were the New York Heart Association class ⩾III and ejection fraction ⩽35% on guideline-directed medical and device therapy. The New York Heart Association class, quality of life, and 6-min hall walk distance were assessed in all patients. Twelve patients underwent cardiopulmonary exercise testing before and 8.9 ± 6.4 months after initiation of baroreflex activation therapy.ResultsThe New York Heart Association class and 6-min hall walk distance improved after baroreflex activation therapy, while quality of life remained stable. Weight-adapted peak oxygen uptake increased significantly from 10.1 (8.2-12.9) ml/min/kg to 12.1 (10.4-14.6) ml/min/kg (p = 0.041). Maximal heart rate was stable. Maximal oxygen pulse increased from 9.7 (5.5-11.3) to 9.9 (7.1-12.1) ml/heartbeat (p = 0.047) in 10 patients with low maximal oxygen pulse at baseline (<16.5 ml/heartbeat). There was no significant change in maximal oxygen pulse in the whole cohort. Ventilatory efficiency remained stable.ConclusionWeight-adapted peak oxygen uptake improved after baroreflex activation therapy, pointing to an enhanced exercise capacity. Ventilatory efficiency and heart rate did not change, while oxygen pulse increased in patients with low oxygen pulse at baseline, indicating an improvement in circulatory efficiency, that is, a beneficial effect on stroke volume and peripheral oxygen extraction.

| S-EPMC9619265 | biostudies-literature

Baroreflex activation therapy reduces frequency and duration of hypertension-related hospitalizations in patients with resistant hypertension.

Project description:PurposeBaroreflex activation therapy (BAT) has been shown to lower blood pressure in patients with resistant hypertension. The purpose of this study was to analyze whether this translates into a reduction of more relevant clinical endpoints.MethodsPatients with resistant hypertension were treated with the second-generation BAT system. Records on hospitalization (dates of admission and discharge, main diagnosis) were obtained from medical insurance companies.ResultsRecords on hospitalization were available for a period of 1 year before BAT in two patients and 2 years in 22 patients. The total number of hospitalizations per patient was 3.3 ± 3.5/year before BAT and 2.2 ± 2.7/year after BAT (p = 0.03). Hospitalizations related to hypertension were significantly decreased from 1.5 ± 1.6/year before BAT to 0.5 ± 0.9/year after BAT (p < 0.01). The cumulative duration of hypertension-related hospital stays was significantly reduced from 8.0 ± 8.7 days/year before BAT to 1.8 ± 4.8 days/year after BAT (p < 0.01). Office cuff blood pressure was 183 ± 27 mmHg over 102 ± 17 mmHg under 6.6 ± 2.0 antihypertensive drugs before BAT and 157 ± 32 mmHg over 91 ± 20 mmHg (both p < 0.01) under 5.9 ± 1.9 antihypertensive drugs (p = 0.09 for number of drugs) at latest follow-up. Daytime ambulatory blood pressure was 164 ± 21 mmHg over 91 ± 14 mmHg before BAT and 153 ± 21 mmHg (p = 0.03) over 89 ± 15 mmHg (p = 0.56) at latest follow-up. Heart rate was 75 ± 16 bpm before BAT and 72 ± 12 bpm at latest follow-up (p = 0.35).ConclusionsRate and duration of hypertension-related hospitalizations in patients with severe resistant hypertension were lowered after BAT. Whether the response is mediated through improvements in blood pressure control requires further studies.

| S-EPMC8302539 | biostudies-literature

Baroreflex activation therapy: a new approach to the management of advanced heart failure with reduced ejection fraction.

Project description:: Chronic heart failure is a common clinical condition characterized by persistent excessive sympathetic nervous system activation. The derangement of the sympathetic activity has relevant implications for disease progression and patient survival. Aiming to positively impact patient outcome, autonomic nervous system modulatory therapies have been developed and tested in animal and clinical studies. As a general gross assumption, direct vagal stimulation and baroreflex activation are considered equivalent. This assumption does not take into account the fact that direct cervical vagal nerve stimulation involves activation of both afferent and efferent fibers innervating not only the heart, but the entire visceral system, leading to undesired responses to and from this compartment. The different action of baroreflex activation is based on generating a centrally mediated reduction of sympathetic outflow and increasing parasympathetic activity to the heart via a physiological reflex pathway. Thus, baroreflex activation rebalances the unbalanced autonomic nervous system via a specific path. Independent and complementary investigations have shown that sympathetic nerve activity can be rebalanced via control of the arterial baroreflex in heart failure patients.Results from recent pioneering research studies support the hypothesis that baroreflex activation can add significant therapeutic benefit on top of guideline-directed medical therapy in patients with advanced heart failure. In the present review, baroreflex activation therapy results are discussed, focusing on critical aspects like patient selection rationale to support clinician orientation in opting for baroreflex activation therapy when, on top of current guideline-directed medical treatment, other therapies are to be considered.

| S-EPMC5555968 | biostudies-literature

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