RESUMEN
Importance: Evidence is lacking from randomized clinical trials of hypoglossal nerve stimulation in obstructive sleep apnea (OSA). Objective: To evaluate the safety and effectiveness of targeted hypoglossal nerve stimulation (THN) of the proximal hypoglossal nerve in patients with OSA. Design, Setting, and Participants: This randomized clinical trial (THN3) was conducted at 20 centers and included 138 patients with moderate to severe OSA with an apnea-hypopnea index (AHI) of 20 to 65 events per hour and body mass index (calculated as weight in kilograms divided by height in meters squared) of 35 or less. The trial was conducted from May 2015 through June 2018. Data were analyzed from January 2022 through January 2023. Intervention: Implant with THN system; randomized 2:1 to activation at month 1 (treatment) or month 4 (control). All received 11 months of THN with follow-up at months 12 and 15, respectively. Main Outcomes and Measures: Primary effectiveness end points comprised AHI and oxygen desaturation index (ODI) responder rates (RRs). Treatment responses at months 4 and 12/15 were defined as a 50% or greater reduction in AHI to 20 or less per hour and an ODI decrease of 25% or greater. Coprimary end points comprised (1) month 4 AHI and ODI RR in the treatment greater than the control group and (2) month 12/15 AHI and ODI RR in the entire cohort exceeding 50%. Secondary end points included sleep apnea severity (AHI and ODI) and patient-reported outcomes (Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, and EQ-5D visual analog scale). Results: Among 138 participants, the mean (SD) age was 56 (9) years, and 19 (13.8%) were women. Month 4 THN RRs were substantially greater in those in the treatment vs control group (AHI, 52.3% vs 19.6%; ODI, 62.5% vs 41.3%, respectively) with treatment-control standardized mean differences of 0.725 (95% CI, 0.360-1.163) and 0.434 (95% CI, 0.070-0.843) for AHI and ODI RRs, respectively. Months 12/15 RRs were 42.5% and 60.4% for AHI and ODI, respectively. Improvements in AHI, ODI, Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, and EQ-5D visual analog scale scores were all clinically meaningful (medium to large effect size). Two serious adverse events and 100 nonserious related adverse events were observed from the implant procedure or study protocol. Conclusions and Relevance: This randomized clinical trial found that THN demonstrated improvements in sleep apnea, sleepiness, and quality of life in patients with OSAs over an extended AHI and body mass index range without prior knowledge of pharyngeal collapse pattern. Clinically meaningful improvements in AHI and patient-reported responses compared favorably with those of distal hypoglossal nerve stimulation trials, although clinically meaningful differences were not definitive for ODI. Trial Registration: ClinicalTrials.gov Identifier: NCT02263859.
Asunto(s)
Síndromes de la Apnea del Sueño , Apnea Obstructiva del Sueño , Humanos , Femenino , Persona de Mediana Edad , Masculino , Nervio Hipogloso/fisiopatología , Calidad de Vida , Somnolencia , Apnea Obstructiva del Sueño/terapia , Apnea Obstructiva del Sueño/fisiopatologíaRESUMEN
Obstructive sleep apnea (OSA) affects nearly 1 billion people worldwide, including approximately 35 million US residents. OSA has detrimental cardiovascular and neurocognitive consequences. Positive airway pressure corrects sleep disordered breathing but is not always tolerated or used sufficiently. Oral appliances and surgery provide alternatives in select populations but are variably effective. Hypoglossal nerve stimulation can effectively treat obstructive sleep apnea. Targeted hypoglossal nerve stimulation (THN) is simpler than incumbent technology with no sensor and an easier, proximal electrode implantation. The third clinical study of THN, THN3, was the first randomized, controlled trial of hypoglossal nerve stimulation to demonstrate significant improvement of sleep disordered breathing in OSA. The present investigation reports the design of a novel trial of targeted stimulation to provide additional Level 1 evidence in moderate to severe obstructive apnea. OSPREY is a randomized, parallel-arm, 13-month trial wherein all subjects are implanted, 2/3 are activated at Month 1 ("Treatment") and 1/3 are activated at Month 7 ("Control"). The primary endpoint is the difference in apnea-hypopnea index response rates between Treatment and Control groups at Month 7. Secondary endpoints include quality of life and oximetry metrics. OSPREY follows an adaptive "Goldilocks" design which optimizes the number of subjects with the need for high-confidence results. A maximum of 150 subjects is allowed, at which study power of >95% is predicted. Interim analyses begin once 50 patients are randomized and recur after each 20 additional randomizations to detect early success or futility. OSPREY is a unique, efficient trial that should provide high-confidence confirmation of the safety and efficacy of targeted hypoglossal nerve stimulation for moderate to severe obstructive sleep apnea.
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Terapia por Estimulación Eléctrica , Apnea Obstructiva del Sueño , Humanos , Nervio Hipogloso , Oximetría , Calidad de VidaRESUMEN
Background: The auricular branch of the vagus nerve runs superficially, which makes it a favorable target for non-invasive stimulation techniques to modulate vagal activity. For this reason, there have been many early-stage clinical trials on a diverse range of conditions. These trials often report conflicting results for the same indication. Methods: Using the Cochrane Risk of Bias tool we conducted a systematic review of auricular vagus nerve stimulation (aVNS) randomized controlled trials (RCTs) to identify the factors that led to these conflicting results. The majority of aVNS studies were assessed as having "some" or "high" risk of bias, which makes it difficult to interpret their results in a broader context. Results: There is evidence of a modest decrease in heart rate during higher stimulation dosages, sometimes at above the level of sensory discomfort. Findings on heart rate variability conflict between studies and are hindered by trial design, including inappropriate washout periods, and multiple methods used to quantify heart rate variability. There is early-stage evidence to suggest aVNS may reduce circulating levels and endotoxin-induced levels of inflammatory markers. Studies on epilepsy reached primary endpoints similar to previous RCTs testing implantable vagus nerve stimulation therapy. Preliminary evidence shows that aVNS ameliorated pathological pain but not evoked pain. Discussion: Based on results of the Cochrane analysis we list common improvements for the reporting of results, which can be implemented immediately to improve the quality of evidence. In the long term, existing data from aVNS studies and salient lessons from drug development highlight the need for direct measures of local neural target engagement. Direct measures of neural activity around the electrode will provide data for the optimization of electrode design, placement, and stimulation waveform parameters to improve on-target engagement and minimize off-target activation. Furthermore, direct measures of target engagement, along with consistent evaluation of blinding success, must be used to improve the design of controls-a major source of concern identified in the Cochrane analysis. The need for direct measures of neural target engagement and consistent evaluation of blinding success is applicable to the development of other paresthesia-inducing neuromodulation therapies and their control designs.
RESUMEN
Baroreflex activation therapy (BAT) is a device-based therapy for patients with treatment-resistant hypertension. In a randomized, controlled trial, the first-generation system significantly reduced blood pressure (BP) versus sham. Although an open-label validation study of the second-generation system demonstrated similar BP reductions, controlled data are not presently available. Therefore, this investigation compares results of first- and second-generation BAT systems. Two cohorts of first-generation BAT system patients were generated with propensity matching to compare against the validation group of 30 second-generation subjects. The first cohort was drawn from the first-generation randomized trial sham group and the second cohort from the active therapy group. Safety and efficacy were compared for the second-generation group relative to the first generation. At 6 months, second-generation BAT outperformed first-generation sham systolic BP reduction by 20 ± 28 mm Hg (mean ± standard deviation, P = .008), while BP reduction in first- and second-generation active groups was similar. At 12 months, efficacy was comparable between all three groups after the sham group had received 6 months of therapy; 47% of second-generation patients achieved goal systolic BP of 140 mm Hg or less after 12 months, comparable to 50% of patients at goal in the first-generation group (P > .999). Implant procedure time, system/procedural safety, and pulse generator longevity improved with the second-generation system. Propensity-matched cohort analysis of the first- and second-generation BAT systems suggests similar therapeutic benefit and superior BP reduction of the second-generation system relative to sham control. Implantation procedure duration and perioperative safety were improved with the second-generation device. These findings should be validated in a prospective randomized trial.
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Vasoespasmo Coronario/terapia , Terapia por Estimulación Eléctrica/instrumentación , Terapia por Estimulación Eléctrica/métodos , Electrodos Implantados , Hipertensión/terapia , Anciano , Antihipertensivos/uso terapéutico , Barorreflejo/fisiología , Determinación de la Presión Sanguínea , Terapia por Estimulación Eléctrica/efectos adversos , Diseño de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Puntaje de Propensión , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The purpose of this publication is to describe the intraoperative experience along with long-term safety and efficacy of the second-generation baroreflex activation therapy (BAT) system in patients with heart failure (HF) and reduced ejection fraction HF (HFrEF). In a randomized trial of New York Heart Association Class III HFrEF, 140 patients were assigned 1:1 to receive BAT plus medical therapy or medical therapy alone. Procedural information along with safety and efficacy data were collected and analyzed over 12 months. Within the cohort of 71 patients randomized to BAT, implant procedure time decreased with experience, from 106 ± 37 minutes on the first case to 83 ± 32 minutes on the third case. The rate of freedom from system- and procedure-related complications was 86% through 12 months, with the percentage of days alive without a complication related to system, procedure, or underlying cardiovascular condition identical to the control group. The complications that did occur were generally mild and short-lived. Overall, 12 months therapeutic benefit from BAT was consistent with previously reported efficacy through 6 months: there was a significant and sustained beneficial treatment effect on New York Heart Association functional Class, quality of life, 6-minute hall walk distance, plasma N-terminal pro-brain natriuretic peptide, and systolic blood pressure. This was true for the full trial cohort and a predefined subset not receiving cardiac resynchronization therapy. There is a rapid learning curve for the specialized procedures entailed in a BAT system implant. BAT system implantation is safe with the therapeutic benefits of BAT in patients with HFrEF being substantial and maintained for at least 1 year.
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Barorreflejo , Seno Carotídeo/inervación , Terapia por Estimulación Eléctrica , Insuficiencia Cardíaca/terapia , Implantación de Prótesis , Volumen Sistólico , Función Ventricular Izquierda , Biomarcadores/sangre , Terapia por Estimulación Eléctrica/efectos adversos , Terapia por Estimulación Eléctrica/instrumentación , Tolerancia al Ejercicio , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/fisiopatología , Humanos , Neuroestimuladores Implantables , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Complicaciones Posoperatorias/etiología , Implantación de Prótesis/efectos adversos , Implantación de Prótesis/instrumentación , Calidad de Vida , Recuperación de la Función , Factores de Tiempo , Resultado del TratamientoRESUMEN
AIMS: Baroreflex activation therapy (BAT) has recently been shown to reduce muscle sympathetic nerve activity and hospitalization rate while improving clinical variables through 6 months of therapy in patients with heart failure and reduced ejection fraction (HFrEF). The objective of the present study is to extend the information on this patient cohort over a long-term follow-up. METHODS AND RESULTS: Eleven patients were enrolled in the study and presented with optimized, stable medical therapy, New York Heart Association Class III HFrEF with left ventricular ejection fraction 40% or less, impaired functional capacity and no active cardiac resynchronization therapy. For the present report, muscle sympathetic nerve activity, baroreflex sensitivity data and hospitalization rate together with standard clinical data were collected at 12 and 21.5â±â4.2 months following BAT activation. Two patients died during long-term follow-up. The remaining nine patients maintained the improvements observed at 6 months, including reduced sympathetic activity and rates of hospitalization. CONCLUSION: BAT provides long-term chronic reductions in sympathetic activity and utilization of hospital resources in patients with HFrEF. General clinical presentation, quality of life and functional capacity are likewise improved and maintained. The temporal association of BAT with sympathetic drive diminution and improvement in objective clinical measures suggests a cause-and-effect relationship that will be verified in future randomized controlled trials of outcome.
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Barorreflejo/fisiología , Terapia por Estimulación Eléctrica , Insuficiencia Cardíaca/terapia , Sistema Nervioso Simpático/fisiopatología , Disfunción Ventricular Izquierda/fisiopatología , Anciano , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/fisiopatología , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Volumen Sistólico , Factores de TiempoRESUMEN
OBJECTIVES: The objective of this clinical trial was to assess the safety and efficacy of carotid BAT in advanced HF. BACKGROUND: Increased sympathetic and decreased parasympathetic activity contribute to heart failure (HF) symptoms and disease progression. Baroreflex activation therapy (BAT) results in centrally mediated reduction of sympathetic outflow and increased parasympathetic activity. METHODS: Patients with New York Heart Association (NYHA) functional class III HF and ejection fractions ≤35% on chronic stable guideline-directed medical therapy (GDMT) were enrolled at 45 centers in the United States, Canada, and Europe. They were randomly assigned to receive ongoing GDMT alone (control group) or ongoing GDMT plus BAT (treatment group) for 6 months. The primary safety end point was system- and procedure-related major adverse neurological and cardiovascular events. The primary efficacy end points were changes in NYHA functional class, quality-of-life score, and 6-minute hall walk distance. RESULTS: One hundred forty-six patients were randomized, 70 to control and 76 to treatment. The major adverse neurological and cardiovascular event-free rate was 97.2% (lower 95% confidence bound 91.4%). Patients assigned to BAT, compared with control group patients, experienced improvements in the distance walked in 6 min (59.6 ± 14 m vs. 1.5 ± 13.2 m; p = 0.004), quality-of-life score (-17.4 ± 2.8 points vs. 2.1 ± 3.1 points; p < 0.001), and NYHA functional class ranking (p = 0.002 for change in distribution). BAT significantly reduced N-terminal pro-brain natriuretic peptide (p = 0.02) and was associated with a trend toward fewer days hospitalized for HF (p = 0.08). CONCLUSIONS: BAT is safe and improves functional status, quality of life, exercise capacity, N-terminal pro-brain natriuretic peptide, and possibly the burden of heart failure hospitalizations in patients with GDMT-treated NYHA functional class III HF. (Barostim Neo System in the Treatment of Heart Failure; NCT01471860; Barostim HOPE4HF [Hope for Heart Failure] Study; NCT01720160).
Asunto(s)
Barorreflejo , Terapia por Estimulación Eléctrica/métodos , Anciano , Barorreflejo/fisiología , Femenino , Insuficiencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Implantación de Prótesis/métodos , Volumen Sistólico/fisiología , Resultado del TratamientoRESUMEN
AIMS: Increased sympathetic and decreased parasympathetic activity contribute to heart failure (HF) symptoms and disease progression. Carotid baroreceptor stimulation (baroreflex activation therapy, BAT) results in centrally mediated reduction of sympathetic and increase in parasympathetic activity. Because patients treated with cardiac resynchronization therapy (CRT) may have less sympathetic/parasympathetic imbalance, we hypothesized that there would be differences in the response to BAT in patients with CRT vs. those without CRT. METHODS AND RESULTS: New York Heart Association (NYHA) Class III patients with an ejection fraction (EF) ≤35% were randomized (1 : 1) to ongoing guideline-directed medical and device therapy (GDMT, control) or ongoing GDMT plus BAT. Safety endpoint was system-/procedure-related major adverse neurological and cardiovascular events (MANCE). Efficacy endpoints were Minnesota Living with Heart Failure Quality of Life (QoL), 6-min hall walk distance (6MHWD), N-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), and HF hospitalization rate. In this sample, 146 patients were randomized (70 control; 76 BAT) and were 140 activated (45 with CRT and 95 without CRT). MANCE-free rate at 6 months was 100% in CRT and 96% in no-CRT group. At 6 months, in the no-CRT group, QoL score, 6MHWD, LVEF, NT-proBNP and HF hospitalizations were significantly improved in BAT patients compared with controls. Changes in efficacy endpoints in the CRT group favoured BAT; however, the improvements were less than in the no-CRT group and were not statistically different from control. CONCLUSIONS: BAT is safe and significantly improved QoL, exercise capacity, NTpro-BNP, EF, and rate of HF hospitalizations in GDMT-treated NYHA Class III HF patients. These effects were most pronounced in patients not treated with CRT.
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Barorreflejo , Terapia por Estimulación Eléctrica , Insuficiencia Cardíaca/terapia , Anciano , Barorreflejo/fisiología , Terapia de Resincronización Cardíaca , Femenino , Insuficiencia Cardíaca/fisiopatología , Humanos , Neuroestimuladores Implantables , Masculino , Persona de Mediana Edad , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
OBJECTIVE: The purpose of this study is to simulate the cost-effectiveness and the long-term clinical performance of the Barostim neo System for the treatment of resistant hypertension when compared to optimal medical treatment. METHODS: A decision analytic model with a combination of a decision tree and Markov process was used to evaluate the cost-effectiveness of Barostim. The clinical effectiveness of Barostim was based on the results of the randomized, placebo-controlled Rheos trial and the follow-up substudy of the DEBuT-HT trial. The cost-effectiveness was modelled from a German societal perspective over a lifetime horizon. Patients with high SBP levels have an increased risk of myocardial infarction, stroke, heart failure and end-stage renal disease. RESULTS: In a simulated cohort of 50-year-old patients at high risk of end-organ damage, Barostim therapy generated 1.66 additional life-years and 2.17 additional quality-adjusted life years with an incremental cost of &OV0556;16â891 when compared with continuation of medical management. Barostim was estimated to be cost-effective compared with optimal medical treatment with an incremental cost-effectiveness ratio of &OV0556;7â797/QALY. In the model, Barostim reduced over a lifetime the rates of myocardial infarction by 19%, stroke by 35%, heart failure by 12% and end-stage renal disease by 23%. The cost-effectiveness of Barostim can be greater in younger patients with resistant hypertension and in patients with significant risk factors for end-organ damage. CONCLUSION: Barostim may be a cost-effective treatment when compared with optimal medical management in patients with resistant hypertension.
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Arterias Carótidas/inervación , Terapia por Estimulación Eléctrica/economía , Hipertensión/economía , Hipertensión/terapia , Presorreceptores/fisiopatología , Simulación por Computador , Análisis Costo-Beneficio , Técnicas de Apoyo para la Decisión , Terapia por Estimulación Eléctrica/efectos adversos , Europa (Continente) , Humanos , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Años de Vida Ajustados por Calidad de VidaRESUMEN
A patient experiencing chronic New York Heart Association (NYHA) Class III heart failure with reduced left ventricular ejection fraction and signs of right ventricular dysfunction is treated with baroreflex activation therapy (BAT). Despite optimal medical therapy, the patient had repeatedly decompensated and was approaching a refractory terminal stage. BAT chronically reduced muscle sympathetic nerve activity and dramatically improved clinical presentation of the patient to NYHA Class I through 12 months of therapy. BAT may hold promise for patients with advanced heart failure and reduced ejection fraction who have exhausted conventional therapy options.
RESUMEN
Sympathoactivation is a prominent feature of heart failure (HF). Its role in cardiac remodeling and arrhythmogenesis is well-recognized today, although incomplete understanding of autonomic mechanisms was a barrier to development of contemporary medical therapies. Despite widespread availability of drugs and devices, mortality and morbidity in HF remain unacceptably high. Recognition of an additional phenotype, HF with preserved ejection fraction (EF), poses additional challenges. New treatment options are required. Electrical modulation of the central nervous system with baroreflex activation therapy offers a new approach. Activation of this afferent pathway induces the central nervous system to rebalance autonomic modulation of the cardiovascular system. Results in animal models of HF demonstrating increased survival and beneficial cardiac remodeling recently led to a clinical feasibility study in HF with reduced EF wherein the clinical course of patients dramatically improved. Results in resistant hypertension patients further suggest potential for benefit in HF with preserved EF.
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Sistema Nervioso Autónomo/fisiología , Insuficiencia Cardíaca , Corazón Auxiliar , Presorreceptores/fisiología , Remodelación Ventricular/fisiología , Animales , Sistema Nervioso Autónomo/efectos de los fármacos , Modelos Animales de Enfermedad , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/cirugía , Humanos , Presorreceptores/efectos de los fármacos , Remodelación Ventricular/efectos de los fármacosRESUMEN
AIMS: Heart failure (HF) pathophysiology is believed to be mediated by autonomic dysfunction, including chronic sympathoexcitation and diminished baroreflex sensitivity, which correlate with mortality risk. Baroreflex activation therapy (BAT) is a device-based treatment providing chronic baroreflex activation through electrical stimulation of the carotid sinus. BAT chronically reduces sympathetic activity in resistant hypertension. The purpose of this investigation is to determine BAT effects in clinical HF. METHODS AND RESULTS: In a single-centre, open-label evaluation, patients with NYHA class III HF, EF <40%, optimized medical therapy, and ineligible for cardiac resynchronization received BAT for 6 months. Efficacy was assessed with serial measurement of muscle sympathetic nerve activity (MSNA) and clinical measures of quality of life and functional capacity. Eleven patients participated in the trial. MSNA was reduced over 6 months from 45.1 ± 7.7 to 31.3 ± 8.3 bursts/min and from 67.6 ± 12.7 to 45.1 ± 11.6 bursts/100 heartbeats, decreases of 31% and 33%, respectively (P < 0.01). Concomitant improvements occurred in baroreflex sensitivity, EF, NYHA class, quality of life and 6 min hall walk (6 MHW) distance (P ≤ 0.05 each). On an observational basis, hospitalization and emergency department visits for worsening HF were markedly reduced. One complication, perioperative anaemia requiring transfusion, occurred during the study. CONCLUSION: BAT was safe and provided chronic improvement in MSNA and clinical variables. Based on present understanding of HF pathophysiology, these results suggest that BAT may improve outcome in HF by modulating autonomic balance. Prospective, randomized trials to test the hypothesis are warranted.
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Barorreflejo/fisiología , Terapia de Resincronización Cardíaca/métodos , Insuficiencia Cardíaca/fisiopatología , Hemodinámica/fisiología , Sistema Nervioso Simpático/fisiopatología , Anciano , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/terapia , Humanos , Masculino , Estudios Prospectivos , Resultado del TratamientoRESUMEN
The objective of this study was to assess long-term blood pressure control in resistant hypertension patients receiving baroreflex activation therapy (BAT). Following completion of the randomized Rheos Pivotal Trial, patients participated in open-label, nonrandomized follow-up to assess safety and efficacy of BAT. Blood pressure reductions were measured relative to a pre-implant baseline as well as the results achieved at the completion of 1 year of follow-up in the randomized phase. Clinically significant responder status was assessed according to FDA-mandated criteria. Of the 322 patients implanted, 76% (n = 245) qualified as clinically significant responders, an additional 10% were indeterminate. Among long-term responders receiving BAT, the mean blood pressure drop was 35/16 mm Hg. Medication use was reduced by the end of the randomized phase and remained lower through the follow-up period. Among responders, 55% achieved goal blood pressures (<140 mm Hg or <130 mm Hg in diabetes or kidney disease). Blood pressures of all active patients remained stable from completion of the randomized phase through long-term follow-up. BAT substantially reduced arterial pressure for most patients participating in the Rheos Pivotal Trial. This blood pressure reduction or goal achievement was maintained over long-term follow-up of 22 to 53 months.
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Barorreflejo/fisiología , Presión Sanguínea/fisiología , Terapia por Estimulación Eléctrica/métodos , Hipertensión/terapia , Seno Carotídeo/fisiología , Estudios de Cohortes , Suministros de Energía Eléctrica , Terapia por Estimulación Eléctrica/efectos adversos , Electrodos Implantados , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/mortalidad , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Previous trials have demonstrated clinically significant and durable reductions in arterial pressure from baroreflex activation therapy (BAT), resulting from electrical stimulation of the carotid sinus using a novel implantable device. A second-generation system for delivering BAT, the Barostim neo™ system, has been designed to deliver BAT with a simpler device and implant procedure. METHODS: BAT, delivered with the advanced system, was evaluated in a single-arm, open-label study of patients with resistant hypertension, defined as resting systolic blood pressure (SBP) ≥140 mm Hg despite treatment with ≥3 medications, including ≥1 diuretic. Stable medical therapy was required for ≥4 weeks before establishing pretreatment baseline by averaging two SBP readings taken ≥24 hours apart. RESULTS: Thirty patients enrolled from seven centers in Europe and Canada. From a baseline of 171.7 ± 20.2/99.5 ± 13.9 mm Hg, arterial pressure decreased by 26.0 ± 4.4/12.4 ± 2.5 mm Hg at 6 months. In a subset (n = 6) of patients with prior renal nerve ablation, arterial pressure decreased by 22.3 ± 9.8 mm Hg. Background medical therapy for hypertension was unchanged during follow-up. Three minor procedure-related complications occurred within 30 days of implant. All complications resolved without sequelae. CONCLUSION: BAT delivered with the second-generation system significantly lowers blood pressure in resistant hypertension with stable, intensive background medical therapy, consistent with studies of the first-generation system for electrical activation of the baroreflex, and provides a safety profile comparable to a pacemaker.
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Barorreflejo/fisiología , Terapia por Estimulación Eléctrica/métodos , Hipertensión/terapia , Anciano , Electrodos Implantados , Diseño de Equipo , Femenino , Humanos , Hipertensión/fisiopatología , Riñón/inervación , Masculino , Persona de Mediana Edad , Implantación de Prótesis/métodos , Telemetría , Resultado del TratamientoRESUMEN
The baroreflex, whose role is well-known in short-term blood pressure regulation, has until recently been unexploited as a practical therapy for hypertension. Recent advancements in approach and technology embodied in the Rheos System have enabled chronic electrical activation of the baroreflex. Chronic results from feasibility studies indicate that Rheos Therapy has an acceptable safety profile and may lead to long-term control of pressure in drug-resistant hypertension patients. Other effects include significant reductions in left ventricular mass and left atrial size. The spectrum of therapeutic impact suggests that Rheos Therapy may improve long-term outcomes in drug-resistant hypertension and possibly benefit related populations. Larger-scale study in randomized, controlled trials are ongoing to verify chronic benefits.
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Barorreflejo/fisiología , Estimulación Eléctrica/instrumentación , Hipertensión/terapia , Adulto , Presión Sanguínea/fisiología , Estimulación Eléctrica/métodos , Electrocardiografía , Diseño de Equipo , Europa (Continente) , Estudios de Factibilidad , Femenino , Vaciamiento Gástrico , Frecuencia Cardíaca/fisiología , Ventrículos Cardíacos/anatomía & histología , Humanos , Masculino , Persona de Mediana Edad , América del Norte , Función VentricularRESUMEN
We investigated the effects of the carotid sinus baroreflex on coupling of the left ventricle (LV) and the arterial system in twelve anesthetized dogs, with all nerves and carotid sinus circulation intact and instrumented to measure LV pressure and volume. The Rheos(R) device was used to directly electrically stimulate the carotid sinus baroreceptors. Stimulation resulted in a significant reduction in systolic blood pressure (SBP), 95.6+/-8.1 to 77.3+/-5.3 mmHg (p<0.0001) and heart rate (HR), 85+/-13.2 to 67.2+/-18.8 (p<.001). Cardiac output was unchanged. Ventricular-vascular coupling was determined by the ratio of arterial and ventricular elastance (Ea/Ees). At baseline, Ea/Ees was 1.26+/-0.27 and after stimulation decreased to 0.51+/-0.16 (p<0.001), favoring optimization of metabolic efficiency. This decrease was entirely due to a reduction in Ea while Ees was unchanged. The maintenance of end-diastolic volume (EDV) during stimulation allowed stroke work (SW) to remain unchanged as arterial pressure decreased. Thus mechanical efficiency, described as the ratio of stroke work to pressure-volume area (SW/PVA) increased from baseline of 0.51+/-0.05 to 0.69+/-0.04 (p<0.0001) during baroreceptor stimulation. We conclude that electrical activation of the carotid sinus baroreceptors results in optimization of both energetic and mechanical efficiency and has no acute effect on LV Ees. These novel findings await confirmation in chronically instrumented animals.
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Barorreflejo/fisiología , Seno Carotídeo/fisiología , Animales , Presión Sanguínea/fisiología , Gasto Cardíaco , Diástole/fisiología , Perros , Elasticidad , Estimulación Eléctrica , Frecuencia Cardíaca , Ventrículos Cardíacos/anatomía & histología , Hemodinámica/fisiología , Miocardio/metabolismo , Consumo de Oxígeno , Presión , Sístole/fisiología , Función Ventricular Izquierda/fisiologíaAsunto(s)
Barorreflejo/fisiología , Hipertensión/fisiopatología , Hipertensión/terapia , Neuroestimuladores Implantables , Antihipertensivos/uso terapéutico , Resistencia a Medicamentos/fisiología , Europa (Continente)/epidemiología , Estudios de Factibilidad , Femenino , Humanos , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Estados Unidos/epidemiología , Función Ventricular Izquierda/fisiologíaRESUMEN
INTRODUCTION: Discrimination of ventricular and supraventricular arrhythmias remains one of the major challenges for appropriate implantable defibrillator (ICD) therapy delivery. The electrogram vector timing and correlation (VTC) algorithm was developed for such rhythm discrimination. The VTC algorithm differentiates normally conducted supraventricular beats from abnormally conducted ventricular beats by comparing the timing and correlation of rate and shock channel electrograms. METHODS AND RESULTS: Rate and shock channel electrograms of sinus rhythm and induced arrhythmias were collected from 93 patients during ICD placement. The algorithm was developed using data from 50 patients and prospectively tested in a software model with the remaining 43 patients. A sinus rhythm reference was formed by averaging complexes of the shock channel signal aligned by the peak amplitude of the rate channel. Eight features measuring the amplitude and timing of shock channel signal characteristics were extracted from the reference for comparison. When a high-rate rhythm was detected, the VTC algorithm computed the correlation of the arrhythmia complex features with the reference. Rhythms with a sufficient number of uncorrelated beats were classified as ventricular tachycardia (VT). In a dual-chamber implementation, the VTC algorithm is integrated with ventricular and atrial rate comparison (V>A) and stability above an atrial fibrillation rate threshold. The test set consisted of 117 arrhythmias. Dual-chamber sensitivity was 100% (81/81 VT) and specificity was 97% (35/36 supraventricular tachycardia). Single-chamber analysis demonstrated 99% sensitivity and 97% specificity. CONCLUSION: The VTC algorithm demonstrated high sensitivity and specificity in discriminating between ventricular and supraventricular arrhythmias.