Baroreflex Activation Therapy Research Articles

No improvement in atrial arrhythmia rates in patients on baroreflex activation therapy

Abstract Background Atrial arrhythmias encompass a wide range of abnormal cardiac rhythms including atrial fibrillation, atrial flutter, and atrial tachycardia. Patients with heart failure with reduced ejection fraction (HFrEF) have increased risk of atrial arrhythmias, ultimately leading to increased morbidity. Baroreflex Activation Therapy (BAT) employs an implantable device to increase parasympathetic nervous system activity by stimulating the carotid baroreceptors thereby reducing afterload and heart failure symptoms. In our prior study, BAT therapy has been shown to reduce hospitalization rates in patients with HFrEF. However, the effects of BAT on atrial arrhythmia has never been studied. Objective In this study, we analyzed the effects of BAT on atrial arrhythmia rates in patients with HFrEF. Methods Patients with HFrEF with BAT therapy for at least 12-months at a hospital were retrospectively studied. Inclusion criteria includes implantable cardioverter-defibrillator (ICD) placement of at least 12-months pre- and post-BAT therapy. Additionally, patients diagnosed with atrial arrhythmias prior to the study timeline were excluded. Atrial arrhythmia rates 6 and 12-months pre-BAT therapy and 6 and 12-months post-BAT therapy were compared. Atrial arrhythmia episodes were recorded through ICD interrogation every 1-3 months in the clinic. Of the 31 identified patients on BAT therapy, 11 patients fit the inclusion criteria. For the 11 patients in the study, 3 identified as female and 8 identified as male, 6 identified as white, 4 identified as Hispanic, and 1 identified as African-American with a mean age of 59.8 ± 17.4 years. The average left ventricular ejection fraction pre-BAT therapy was 23.8 ± 10.8%. Results The mean average atrial arrhythmia rates for 6-month pre-BAT therapy and 6-month post-BAT therapy were 0.12/month ± 0.40 and 1.32/month ± 2.76 respectively (p=0.18), suggesting no differences in atrial arrhythmia rates at 6-months with BAT therapy. The mean average atrial arrhythmia rates for 12-month pre-BAT therapy and 12-month post-BAT therapy were 0.11/month ± 0.35 and 2.40/month ± 5.84 respectively (p=0.22), suggesting no differences in atrial arrhythmia rates at 12-months with BAT therapy. Conclusion Although BAT therapy has been shown to decrease hospitalization rates, BAT therapy is not associated with decreased atrial arrhythmia rates at 6 months and 12 months.

Baroreflex activation therapy in heart failure patients with reduced ejection fraction: a long-term follow up

Abstract Introduction Heart failure with reduced ejection fraction (HFrEF) is a major public health concern with substantial morbidity and mortality. Overactivation of the sympathetic nervous system is a key pathophysiological process driving heart failure progression. Baroreceptor activation therapy (BAT) targets this autonomic imbalance and is a promising treatment strategy for patients with HFrEF. Current short-term studies indicate that BAT provides symptomatic relief, improvement in left ventricular function and cardiac biomarkers. However, data regarding the long-term effect of BAT on HFrEF are scarce. Purpose This study aims to assess long-term outcome in HFrEF patients who underwent BAT. Methods Patients with HFrEF who received BAT between 2014-2023 were followed until latest available follow-up. Symptom burden, echocardiography and laboratory testing were assessed before BAT implantation and in subsequent follow ups. Results 23 patients (mean age 66±10 years, 83% men) with HFrEF were included in the study. Etiology of heart failure was ischemic in 70%. The majority of patients (96%) suffered from NYHA III with a mean left ventricular ejection fraction (LVEF) of 23±8% and NTproBNP of 2463±2922pg/ml. Complication occurred in one patient during BAT implantation (4%). Mean follow-up was 3±2 (max. 7.5) years. BAT reduced NYHA classification in 12 patients (52%) after 1 year, of which 1 patient remained in ameliorated NYHA for 7.5 years. Evolution of NYHA functional class over time is shown in Figure 1. Echocardiographic evaluation revealed significant improvement in LVEF of 9±9% after 1 year (p<0.001) and by 11±9% after 2 years (p=0.005). In long-term a trend towards improved LVEF could be observed (Figure 2). In addition, BAT mildly reduced NTproBNP in the first 2 years (after 1 year non-significantly by -396±1006pg/ml and significantly after 2 years by -566±651pg/ml (p=0.039)). Seven patients reaching recommended replacement time underwent device exchange. Four patients deceased during observation time. Conclusion BAT resulted in a substantial reduction in NYHA classification, improvement in LVEF, and a delayed reduction in NTproBNP levels. These findings highlight the long-term efficacy and potential benefits of BAT as a therapeutic intervention for patients with HFrEF.Sankey plot of NYHA class over timeAlteration of LVEF over time

A sham-controlled randomised pilot trial on baroreflex activation therapy in patients with resistant hypertension: What will the future hold?

A sham-controlled randomised pilot trial on baroreflex activation therapy in patients with resistant hypertension: What will the future hold?

Baroreflex activation therapy in advanced heart failure: A long-term follow-up.

Baroreceptor activation therapy (BAT) is a promising new treatment strategy for patients with heart failure with reduced ejection fraction (HFrEF). It provides symptomatic relief, improvement in left ventricular function and reduction of cardiac biomarkers. Data regarding the long-term effect of BAT on HFrEF are scarce. This retrospective, monocentric study aimed to assess long-term outcome in patients who underwent BAT. Patients with HFrEF who received BAT at Hannover Medical School between 2014 and 2023 were followed until the latest available follow-up. Symptom burden, echocardiography and laboratory testing were assessed before BAT implantation and in subsequent follow-ups. Twenty-three patients (mean age 66±10years, 83% male) with HFrEF were included in the study. Aetiology of heart failure was ischaemic in 70%. The majority of patients (96%) suffered from New York Heart Association (NYHA) III with a mean left ventricular ejection fraction (LVEF) of 23±8% and N-terminal pro-B-type natriuretic peptide (NT-proBNP) of 2463±2922pg/mL. A complication occurred in one patient during BAT implantation (4%). The mean follow-up was 3±2 (max. 7.5) years. BAT reduced NYHA classification in 12 patients (52%) after 1year, of which one patient remained in ameliorated NYHA for 7.5years. Echocardiographic evaluation revealed significant improvement in LVEF by 9±9% after 1year (P<0.001) and by 11±9% (P=0.005) after 2years. In addition, BAT mildly reduced NT-proBNP in the first 2years [non-significantly after 1year by 396±1006pg/mL and significantly after 2years by 566±651pg/mL (P=0.039)]. Seven patients reaching the recommended replacement time underwent device exchange. Four patients died during observation time. BAT resulted in a substantial reduction in NYHA classification and improvement in LVEF that lasted over long-term follow-up in many patients. NT-proBNP level decreased interim in long-term follow-up. These findings highlight the long-term efficacy and potential benefits of BAT as a therapeutic intervention for patients with HFrEF.

ID: 323236 IDentifying Off-Target Activation Pathways for Baroreflex Activation Therapy (BAT) in Swine

ID: 323236 IDentifying Off-Target Activation Pathways for Baroreflex Activation Therapy (BAT) in Swine

Sham-Controlled Randomized Pilot Trial on Baroreflex Activation Therapy in Resistant Hypertension.

Sham-Controlled Randomized Pilot Trial on Baroreflex Activation Therapy in Resistant Hypertension.

Effects of baroreflex activation therapy on cardiac function and morphology.

Arterial hypertension (aHTN) plays a fundamental role in the pathogenesis and prognosis of heart failure with preserved ejection fraction (HFpEF). The risk of heart failure increases with therapy-resistant arterial hypertension (trHTN), defined as inadequate blood pressure (BP) control ≥140/90mmHg despite taking ≥3 antihypertensive medications including a diuretic. This study investigates the effects of the BP lowering baroreflex activation therapy (BAT) on cardiac function and morphology in patients with trHTN with and without HFpEF. Sixty-four consecutive patients who had been diagnosed with trHTN and received BAT implantation between 2012 and 2016 were prospectively observed. Office BP, electrocardiographic and echocardiographic data were collected before and after BAT implantation. Mean patients' age was 59.1years, 46.9% were male, and mean body mass index (BMI) was 33.2kg/m2. The prevalence of diabetes mellitus was 38.8%, atrial fibrillation was 12.2%, and chronic kidney disease (CKD) stage ≥3 was 40.8%. Twenty-eight patients had trHTN with HFpEF, and 21 patients had trHTN without HFpEF. Patients with HFpEF were significantly older (64.7 vs. 51.6years, P<0.0001), had a lower BMI (30.0 vs. 37.2kg/m2, P<0.0001), and suffered more often from CKD-stage ≥3 (64 vs. 20%, P=0.0032). After BAT implantation, mean office BP dropped in patients with and without HFpEF (from 169±5/86±4 to 143±4/77±3mmHg [P=0.0019 for systolic BP and 0.0403 for diastolic BP] and from 170±5/95±4 to 149±6/88±5mmHg [P=0.0019 for systolic BP and 0.0763 for diastolic BP]), while a significant reduction of the intake of calcium-antagonists, α2-agonists and direct vasodilators, as well as a decrease in average dosage of ACE-inhibitors and α2-agonists could be seen. Within the study population, a decrease in heart rate from 74 ± 2 to 67 ± 2 min-1 (P=0.0062) and lengthening of QRS-time from 96±3 to 106±4ms (P=0.0027) and QTc-duration from 422±5 to 432±5ms (P=0.0184) were detectable. The PQ duration was virtually unchanged. In patients without HF, no significant changes of echocardiographic parameters could be seen. In patients with HFpEF, posterior wall diameter decreased significantly from 14.0±0.5 to 12.7±0.3mm (P=0.0125), left ventricular mass (LVM) declined from 278.1±15.8 to 243.9±13.4g (P=0.0203), and e' lateral increased from 8.2±0.4 to 9.0±0.4cm/s (P=0.0471). BAT reduced systolic and diastolic BP and was associated with morphological and functional improvement of HFpEF.

An Overview of Electrical Nerve Stimulation via Transdermal Application

The risk of dying from cardiovascular and cerebrovascular diseases is significantly increased by hypertension. The primary issues affecting public health at the moment are hypertension and its consequences. Some persons with hypertension, even under intensive therapeutic supervision, do not achieve the specified blood pressure (BP) treatment targets. Patients with resistant hypertension (RH) may be defined as those who need to take three or more different kinds of antihypertensive medications in order to reach their blood pressure target. Utilizing the body's natural bioelectric system, bioelectric technology is a relatively new approach. In auxiliary evaluation, pain management, and organ function rehabilitation, it is commonly used. Renal sympathetic denervation, carotid baroreflex activation therapy, electroacupuncture in traditional Chinese medicine, and transcutaneous electrical nerve stimulation are the primary forms of bioelectrical technology, which has advanced quickly in recent years as an effective treatment for RH.

Baroreflex activation therapy in patients with heart failure and a reduced ejection fraction: Long-term outcomes.

Carotid baroreflex activation therapy (BAT) restores baroreflex sensitivity and modulates the imbalance in cardiac autonomic function in patients with heart failure with reduced ejection fraction (HFrEF). We tested the hypothesis that treatment with BAT significantly reduces cardiovascular mortality and heart failure morbidity and provides long-term safety and sustainable symptomatic improvement. BeAT-HF was a prospective, multicentre, randomized, two-arm, parallel-group, open-label, non-implanted control trial. New York Heart Association (NYHA) class III subjects, ejection fraction ≤35%, previous heart failure hospitalization or N-terminal pro-B-type natriuretic peptide (NT-proBNP) >400 pg/ml, no class I indication for cardiac resynchronization therapy and NT-proBNP <1600 pg/ml were randomized to BAT plus optimal medical management (BAT group) or optimal medical management alone (control). The primary endpoint was cardiovascular mortality and HF morbidity; additional pre-specified endpoints included durability of safety, quality of life (QOL), exercise capacity (6-min hall walk distance [6MHWD]), functional status (NYHA class), hierarchical composite win ratio, freedom from all-cause death, left ventricular assists device (LVAD) implantation, heart transplant. Overall, 323 patients had 332 primary events, median follow-up was 3.6 years/patient. Both primary endpoint (rate ratio 0.94, 95% confidence interval [CI] 0.57-1.57; p = 0.82) and components of the primary endpoints were not significantly different between BAT and control. The system- and procedure-related major adverse neurological and cardiovascular event-free rate remained 97% throughout the trial. Symptom improvement (QOL, 6MHWD, NYHA class, all nominal p < 0.001) in the BAT group was durable in time, sustainable in extent. Win ratio (1.26, 95% CI 1.02-1.58) and freedom from all-cause death, LVAD implantation, heart transplant (hazard ratio 0.66, 95% CI 0.43-1.01) favoured the BAT group but did not reach statistical significance. The BeAT-HF primary endpoint was neutral; however, BAT provided safe, effective, and sustainable improvements in HFrEF patient's functional status, 6MHWD and QOL.

Early experience with baroreflex activation therapy from a vascular surgery perspective

Baroreflex activation therapy (BAT) is an emerging device-based treatment for patients with heart failure with a reduced ejection fraction refractory to maximally tolerated goal-directed medical therapy. Currently, there is sparse literature on the critical role that vascular surgeons serve in the delivery of this novel therapy. This single-institution series describes the creation of a BAT program and elaborates on the function of vascular surgeons in the multidisciplinary heart failure team. The preoperative evaluation, perioperative care, and postoperative course of patients receiving BAT from March 2022 to August 2023 were retrospectively analyzed. Eleven patients were evaluated by a dedicated heart failure cardiologist for medical eligibility and assessed by a vascular surgeon for technical feasibility. Of the 11 patients, 7 were men (63.6%). The median age was 60.5 years (range, 44-73 years). No patient (0.00%) had existing carotid artery disease, and one patient (9.1%) had undergone previous neck radiation therapy. All 11 patients (100%) had an existing cardiac implantable electronic device, and BAT implantation was performed on the same side as the cardiac implantable electronic device in two patients (18.1%). Four patients (36.4%) required preoperative hospital admission for medical optimization before surgery. The median length of surgery was 82 minutes (range, 58-113 minutes), and the median length of stay in the hospital after surgery was 1 day (range, 0-6 days). No major adverse neurologic or cardiovascular events, cranial nerve injuries, device complications requiring reintervention, or heart failure-related mortality at 6 months occurred. Three patients (27.3%) experienced extraneous stimulations, which affected BAT tolerability. Within 6 months after BAT implantation, no significant improvements were observed for several heart failure disease burden markers compared with 6 months before BAT implantation. Our early results demonstrate that BAT implantation is a safe procedure with rare complications. Vascular surgeons play an important role in the multidisciplinary delivery of this novel device-based therapy. More data are needed to understand whether BAT is beneficial in the treatment of heart failure with a reduced ejection fraction refractory to maximally tolerated goal-directed medical therapy.

Baroreflex activation therapy for heart failure with reduced ejection fraction: A comprehensive systematic review and meta-analysis

BackgroundIn recent years, baroreflex activation therapy (BAT) has been utilized to treat heart failure with reduced ejection fraction (HFrEF). However, the supporting literature on its efficacy and safety is still limited. This investigation elucidates the effects of BAT in HFrEF patients to provide a reference for future clinical applications. MethodsThis investigation follows Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines. Relevant investigations on the use of BAT in HFrEF patients were searched and selected from 5 databases, including Web of Science, MEDLINE, PubMed, Embase, and Cochrane Library, from inception to December 2022. The methodological quality of eligible articles was assessed via the Cochrane risk of bias tool, and for meta-analysis, RevMan (5.3) was used. ResultsRandomized controlled trials comprising 343 participants were selected for the meta-analysis, which revealed that in HFrEF patients, BAT enhanced the levels of LVEF (MD: 2.97, 95 % CI: 0.53 to 5.41), MLHFQ (MD: −14.81, 95 % CI: −19.57 to −10.06) and 6MWT (MD: 68.18, 95 % CI: 51.62 to 84.74), whereas reduced the levels of LVEDV (MD: −15.79, 95 % CI: −32.96 to 1.37) and DBP (MD: −2.43, 95 % CI: −4.18 to −0.68). ConclusionIt was concluded that BAT is an efficient treatment option for HFrEF patients. However, to validate this investigation, further randomized clinical trials with multiple centers and large sample sizes are needed.

Advances in device-based treatment of heart failure with preserved ejection fraction: evidence from clinical trials.

Heart failure with preserved ejection fraction (HFpEF) is a group of clinical syndromes that exhibit a remarkably heterogeneous phenotype, characterized by symptoms and signs of heart failure, left ventricular diastolic dysfunction, elevated levels of natriuretic peptides, and an ejection fraction greater than or equal to 50%. With the aging of the population and the escalating prevalence of hypertension, obesity, and diabetes, the incidence of HFpEF is progressively rising. Drug therapy options for HFpEF are currently limited, and the associated high risk of cardiovascular mortality and heart failure rehospitalization significantly impact patients' quality of life and longevity while imposing a substantial economic burden on society. Recent research indicates that certain device-based therapies may serve as valuable adjuncts to drug therapy in patients with specific phenotypes of HFpEF, effectively improving symptoms and quality of life while reducing the risk of readmission for heart failure. These include inter-atrial shunt and greater splanchnic nerve ablation to reduce left ventricular filling pressure, implantable heart failure monitor to guide diuresis, left atrial pacing to correct interatrial dyssynchrony, cardiac contractility modulation to enhance cardiac calcium handling, as well as renal denervation, baroreflex activation therapy, and vagus nerve stimulation to restore the autonomic imbalance. In this review, we provide a comprehensive overview of the mechanisms and clinical evidence pertaining to these devices, with the aim of enhancing therapeutic strategies for HFpEF.

Abstract 18085: Effect of Therapies on Quality of Life in Heart Failure With Reduced Ejection Fraction: A Systematic Review and Meta-Analysis

Introduction: Minnesota Living with Heart Failure (MLWHF) questionnaire is a validated tool to assess quality of life in patients with heart failure with reduced ejection fraction (HFrEF) Hypothesis: We performed this systematic review and meta-analysis to evaluate the effect of therapies on improvement in MLWHF; analyzed across randomized controlled trials (RCTs) of drug based therapy, device based therapy, autonomic modulation, and exercise. Methods: We conducted a systematic search of MEDLINE and EMBASE for RCTs measuring MLWHF at baseline and follow-up in patients with HFrEF. Primary outcome was improvement in MLWHF. Meta-analysis was stratified in groups based on medical therapy, device based therapy (cardiac resynchronization therapy and cardiac contractility modulation), autonomic modulation (vagus nerve stimulation and baroreflex activation therapy), and exercise. Mean difference (MD) with 95% Confidence Interval (CI) were reported across multiple studies included in meta-analysis. Results: A total of 23 studies met the inclusion criteria. Analysis showed statistically significant improvement in MLWHF at follow-up for drug based therapy (MD: -2.77; 95% CI: -5.10, -0.44) (Panel A), device based therapy (MD: -6.86; 95% CI: -9.60, -4.12) (Panel B), autonomic modulation (MD: -15.21; 95% CI: - 19.25, -11.17) (Panel C), and exercise group (MD: -10.05; 95% CI: -16.66, -3.43) (Panel D). Sub-group analyses based on various treatment modalities showed statistically significant improvement in MLWHF at follow-up for cardiac resynchronization therapy (MD: -8.11; 95% CI: -11.88, -4.33), cardiac contractility modulation (MD: -5.47; 95% CI: -9.46, -1.49), and baroreflex activation therapy (MD: -19.79; 95% CI: -24.90, -14.67). Conclusions: Drug based therapy, device based therapy, autonomic modulation, and exercise are associated with improvement in quality of life in patients with HFrEF.

Abstract 13319: The Barostim Baroreflex Activation Therapy System: Safety Insights From FDA MAUDE Database

Introduction: BAROSTIM NEO® is a Baroreflex activation therapy (BAT) system which has been approved recently by FDA for patients with refractory heart failure. Post market experience of BAT related complications and performance issues have not been reported. Objective: To analyze the post-approval device failures and patient related adverse events (AE) associated with Barostim NEO® system using Manufacturer and User Facility Device Experience (MAUDE) database. Methods: A MAUDE database search was conducted on December 7, 2022, for reports received between Jan 1, 2019, to November 30, 2022. Manual search of the MAUDE database conducted using the term “Barostim” in the brand name section. The AE were adjudicated to various categories based on the review of the event description for each medical device report (MDR). Results: A total of 22 events were reported which included MDRs reported by physicians or manufacturer or both. Device related malfunction was reported in 45.5% (n=10) whereas patient related AE reported in 77.3% (n=17) cases. Of total device related AE, material split, cut or torn was most commonly reported problem (32%, n=7), followed by high impedance (13.6%, n=3) and low impedance (9.1%, n=2). Of the patient related AE, 32% (n=7) were related to clinical or subclinical infection, 18.2% (n=4) hematoma, 13.6% (n=3) heart failure or myocardial injury, 9.1% (n=2) stroke/CVA, 9.1% and 9.1% (n=2) twiddler’s syndrome. No carotid artery or jugular injury and procedure related death reported in the study period. The report is limited by the lack of information on the total number of BAT devices implanted across the country. Conclusions: This study provides a wide range of device malfunction and patient related post-approval adverse events for Barostim device which have not been reported in any clinical trial/study before. The reported complications seem to be in line with other cardiac implantable electronic devices and no BAT specific complications were noted.

Effect of Baroreflex Activation Therapy on Blood Pressure: A Randomized Sham Clinical Pilot Trial on Behalf of the BAT Team

Effect of Baroreflex Activation Therapy on Blood Pressure: A Randomized Sham Clinical Pilot Trial on Behalf of the BAT Team

Baroreflex activation therapy in patients with heart failure with reduced ejection fraction: a single-centre experience.

Heart failure with reduced ejection fraction (HFrEF) is associated with excessive sympathetic and impaired parasympathetic activity. The Barostim Neo™ device is used for electronical baroreflex activation therapy (BAT) to counteract autonomic nervous system dysbalance. Randomized trials have shown that BAT improves walking distance and reduces N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels at least in patients with only moderate elevation at baseline. Its impact on the risk of heart failure hospitalization (HFH) and death is not yet established, and experience in clinical routine is limited. We report on patient characteristics and clinical outcome in a retrospective, non-randomized single-centre registry of BAT in HFrEF. Patients in the New York Heart Association (NYHA) Classes III and IV with a left ventricular ejection fraction (LVEF) <35% despite guideline-directed medical therapy were eligible. Symptom burden, echocardiography, and laboratory testing were assessed at baseline and after 12months. Clinical events of HFH and death were recorded at routine clinical follow-up. Data are shown as number (%) or median (inter-quartile range). Between 2014 and 2020, 30 patients were treated with BAT. Median age was 67 (63-77) years, and 27 patients (90%) were male. Most patients (83%) had previous HFH. Device implantation was successful in all patients. At 12months, six patients had died and three were alive but did not attend follow-up. NYHA class was III/IV in 26 (87%)/4 (13%) patients at baseline, improved in 19 patients, and remained unchanged in 5 patients (P<0.001). LVEF improved from 25.5 (20.0-30.5) % at baseline to 30.0 (25.0-36.0) % at 12months (P=0.014). Left ventricular end-diastolic diameter remained unchanged. A numerical decrease in NT-proBNP [3165 (880-8085) vs. 1001 (599-3820) pg/mL] was not significant (P=0.526). Median follow-up for clinical events was 16 (10-33) months. Mortality at 1 (n=6, 20%) and 3years (n=10, 33%) was as expected by the Meta-Analysis Global Group in Chronic Heart Failure risk score. Despite BAT, event rate was high in patients with NYHA Class IV, NT-proBNP levels >1600pg/mL, or estimated glomerular filtration rate (eGFR) <30mL/min at baseline. NYHA class and eGFR were independent predictors of mortality. Patients with HFrEF who are selected for BAT are in a stage of worsening or even advanced heart failure. BAT appears to be safe and improves clinical symptoms and-to a modest degree-left ventricular function. The risk of death remains high in advanced disease stages. Patient selection seems to be crucial, and the impact of BAT in earlier disease stages needs to be established.

Efficacy and safety of baroreflex activation therapy for heart failure with reduced ejection fraction: systematic review.

Baroreflex activation therapy (BAT) is a possible adjuvant treatment for patients with heart failure with reduced ejection fraction (HFrEF) who remain symptomatic despite optimal medical therapy and may be an alternative therapy in patients with contraindications or drug intolerance. Our aim was to evaluate the efficacy and safety of BAT in patients with HFrEF. The protocol for this study was registered with PROSPERO (CRD42022349175). Searches were conducted using MEDLINE, preMedLine (via PubMed), EMBASE, Cochrane Library, Web of Science, Trip Medical Database, WHO International Clinical Trials Registry, and ClinicalTrials.gov. We included randomized controlled trials that compared the effects of BAT with pharmacological treatment. We assessed the risk of bias of each study using the Cochrane RoB2 tool and the certainty of the results using the GRADE approach. We performed a meta-analysis of treatment effects using a fixed-effects or random-effects model, depending on the heterogeneity observed. Two studies were included in the meta-analysis (HOPE4HF and BeAT-HF). The results showed that BAT led to statistically significant improvements in New York Heart Association functional class (relative risk 2.13; 95% confidence interval [CI, 1.65 to 2.76]), quality of life (difference in means -16.97; 95% CI [-21.87 to -12.07]), 6min walk test (difference in means 56.54; 95% CI [55.67 to 57.41]) and N-terminal probrain natriuretic peptide (difference in means -120.02; 95% CI [-193.58 to -46.45]). The system- and procedure-related complication event-free rate varied from 85.9% to 97%. The results show that BAT is safe and improves functional class, quality of life and congestion in selected patients with HFrEF. Further studies and long-term follow-up are needed to assess efficacy in reducing cardiovascular events and mortality.

A Comparative Review of Vagal Nerve Stimulation Versus Baroreceptor Activation Therapy in Cardiac Diseases.

Sympathetic imbalance coupled with impairment of baroreceptor control is a key factor responsible for hemodynamic abnormalities in congestive heart failure. Vagal nerve stimulation (VNS) and baroreceptor activation therapy (BAT) are two novel interventions for the same. In this paper, we review the role of sympathovagal alterations in cardiac diseases like heart failure, arrhythmia, hypertension (HTN), etc. Studies like neural cardiac therapy for heart failure (NECTAR-HF), autonomic regulation therapy to enhance myocardial function and reduce progression of heart failure (ANTHEM-HF), and baroreflex activation therapy for heart failure (BEAT-HF), which comprise the history, efficacy, limitations, and current protocols, were extensively analyzed in contrast to one another. Vagal nerve stimulation reverses the reflex inhibition of cardiac vagal efferent activity, which is caused as a result of sympathetic overdrive during the course for heart failure. It has shown encouraging results in certain pre-clinical studies; however, there is also a possibility of serious cardiovascular adverse events if given in higher than the recommended dosage. Attenuated baroreflex sensitivity is attributed to cardiac arrhythmogenesis during heart failure. Baroreceptor activation therapy reverses this phenomenon. However, the surgical procedure for baroreceptor stimulation can have unwarranted complications, including worsening heart failure and hypertension. Considering the effectiveness of the given modalities and taking into account the inconclusive evidence of their adverse events, more clinical trials are needed for establishing the future prospects of these interventional approaches.

EFFECT OF BAROREFLEX ACTIVATION THERAPY ON BLOOD PRESSURE: THE BAT-STUDY – A RANDOMIZED SHAM CLINICAL PILOT TRIAL

Objective: To explore the effects of baroreflex activation therapy (BAT) on blood pressure in individuals with refractory hypertension. Design and method: This investigator-initiated randomized, double-blinded sham-controlled pilot trial included five Finnish patients with refractory hypertension. Participants were found eligible if they were 18 - 70 years old with a daytime systolic ambulatory blood pressure (ABP) of 145 mmHg or higher, and/or a daytime diastolic ABP of 95 mm Hg or higher. Patients were on 3 or more antihypertensive drugs including a diuretic. A witnessed drug intake prior to ABPM was implemented. The Barostim Neo System was implanted for modulation of the autonomic nervous system by direct electrical stimulation of the carotid baroreceptors. After 1 month following implantation, all participants were randomized to either 8 months of baroreflex activation therapy (BAT-system on) or continuous pharmacotherapy (BAT-system off) followed by continuous BAT-therapy for all participants for 8 months. The complete design is outlined in the Figure. 24-hour ABP-measurements were performed per protocol. The primary outcome was defined as a change in ambulatory systolic blood pressure after 8 months of BAT, compared to pharmacotherapy. Results and conclusions: After 8 months of follow-up BAT decreased mean systolic daytime blood pressure by 11.8 mmHg in three participants randomized to BAT, while in the two remaining participants randomized to continuous pharmacotherapy mean systolic daytime blood pressure increased by 8.7 mmHg. When pooling all daytime systolic 24-hour ABP-measurements across the entire follow-up, BAT-therapy was associated with a 9.2 mmHg lower mean blood pressure as compared to continuous pharmacotherapy (143.5 mmHg [95% CI:142.2 - 144.9] vs 152.7 mmHg [151.1 - 154.2], P &lt; 0.0001). In linear mixed models with the BAT-system's status as a fixed effect, day-time systolic blood pressure recordings from 24-hour ABP-measurements at baseline and after 8 months of follow-up were compared between individuals on BAT and continuous pharmacotherapy. Here, BAT-therapy was associated with a reduction in mean systolic day-time blood pressure of -11.7 mmHg (P &lt; 0.0001). In conclusion, BAT-therapy may be a promising tool in lowering systolic blood pressure in individuals with refractory hypertension. Figure. Study design. ABPM = ambulatory blood pressure measurement. Device = Control of Device.

The role of baroreflex activation therapy in patients with resistant hypertension

Resistant hypertension has become an interesting and controversial topic in the last decade. According to the European Guidelines for the management and treatment of hypertension, resistant hypertension is defined as the lack of blood pressure control despite the control of risk factors and good compliance with a treatment with at least three antihypertensives in the maximum tolerated doses, one of which is a diuretic, at patients in whom possible causes of secondary arterial hypertension were excluded. In the official position of the AHA (American Heart Association) on this subject, resistant HTN is considered as HTN uncontrolled with three antihypertensive drugs or HTN controlled but requiring at least four drugs. Although the medical world has a complex arsenal of antihypertensive preparations, with them it is not possible to correct the values in a good part of the patients. A solution would be the development and study of the effectiveness of baroreflex activation therapy.