Efficacy of Electrical Baroreflex Activation Is Independent of Peripheral Chemoreceptor Modulation.

Arterial baroreflex activation through electrical carotid sinus stimulation has been developed for the treatment of resistant hypertension. Previous studies suggested that the peripheral chemoreflex is tonically active in hypertensive patients and may inhibit baroreflex responses. We hypothesized that peripheral chemoreflex activation attenuates baroreflex efficacy evoked by electrical carotid sinus stimulation. We screened 35 patients with an implanted electrical carotid sinus stimulator. Of those, 11 patients with consistent acute depressor response were selected (7 men/4 women, age: 67±8 years, body mass index: 31.6±5.2 kg/m2, 6±2 antihypertensive drug classes). We assessed responses to electrical baroreflex stimulation during normoxia, isocapnic hypoxia (SpO2: 79.0±1.5%), and hyperoxia (40% end-tidal O2 fraction) by measuring heart rate, blood pressure, ventilation, oxygen saturation, end-tidal CO2 and O2 fractions, and muscle sympathetic nerve activity. During normoxia, baroreflex activation reduced systolic blood pressure from 164±27 to 151±25 mm Hg (mean±SD, P<0.001), heart rate from 64±13 to 61±13 bpm (P=0.002), and muscle sympathetic nerve activity from 42±12 to 36±12 bursts/min (P=0.004). Hypoxia increased systolic blood pressure 8±12 mm Hg (P=0.057), heart rate 10±6 bpm (P<0.001), muscle sympathetic nerve activity 7±7 bursts/min (P=0.031), and ventilation 10±7 L/min (P=0.002). However, responses to electrical carotid sinus stimulation did not differ between hypoxic and hyperoxic conditions: systolic blood pressure: -15±7 versus -14±8 mm Hg (P=0.938), heart rate: -2±3 versus -2±2 bpm (P=0.701), and muscle sympathetic nerve activity: -6±4 versus -4±3 bursts/min (P=0.531). We conclude that moderate peripheral chemoreflex activation does not attenuate acute responses to electrical baroreflex activation therapy in patients with resistant hypertension. These patients provided insight into human baroreflex-chemoreflex interactions that could not be gained otherwise.

Usefulness of Tilt Testing and Carotid Sinus Massage for Evaluating Reflex Syncope.

Thirty years ago Tilt Testing (TT) was described as a tool in the diagnostic work-up of vasovagal syncope; after its initial success, some flaws have become evident. The concept of hypotensive susceptibility has provided the test a new relevance, shifting from diagnosis only, to therapeutic management. Carotid Sinus Massage (CSM) was introduced at the beginning of the XX century; the technique has evolved over years, whereas the concept of carotid sinus syndrome (CSS) has remained unchanged and uncontested for more than half a century. Nowadays, CSS is a matter of debate, with new classifications and criteria coming on the scene. Recently, a common central etiological mechanism has been hypothesized for reflex syncope, manifesting as CSS, vasovagal syncope or both. In this context, TT and CSM acquire an important role in clinical practice, being essential for a complete diagnosis and treatment. Recalling their historical background, the present paper illustrates an actual interpretation of TT and CSM.

Endovascular Baroreflex Amplification for Resistant Hypertension.

PURPOSE OF REVIEW: Most hypertension devices have been designed to interrupt or modify the sympathetic nervous system, which seems to be unbalanced in hypertension. Carotid baroreceptors play a pivotal role in maintaining adrenergic balance via a direct feedback interface and would be an exceptional target for intervention. The purpose of this review is to define the role of the baroreceptor in hypertension, to examine device-based therapies targeting the baroreflex and to explore future promises of endovascular baroreflex amplification (EBA). RECENT FINDINGS: In the last two decades, two therapeutic strategies targeting the carotid baroreceptor have evolved: baroreflex activation therapy (BAT) and EBA. Both therapies enhance baroreceptor activity, either directly by electrical stimulation or indirectly by changing the geometric shape of the carotid sinus and increasing pulsatile wall strain. By showing a significant, sympathetic inhibition-mediated effect on blood pressure, BAT has laid the foundation for baroreflex-targeting therapies for resistant hypertension. EBA is a less invasive therapy with promising first-in-man study results. Ongoing randomized sham-controlled trials are needed to better understand efficacy, durability, and long-term safety and define phenotypes that may most benefit from this treatment.

Carotid sinus hypersensitivity: block of the sternocleidomastoid muscle does not affect responses to carotid sinus massage in healthy young adults.

The arterial baroreflex is crucial for short-term blood pressure control - abnormal baroreflex function predisposes to syncope and falling. Hypersensitive responses to carotid baroreflex stimulation using carotid sinus massage (CSM) are common in older adults and may be associated with syncope. The pathophysiology of this hypersensitivity is unknown, but chronic denervation of the sternocleidomastoid muscles is common in elderly patients with carotid sinus hypersensitivity (CSH), and is proposed to interfere with normal integration of afferent firing from the carotid baroreceptors with proprioceptive feedback from the sternocleidomastoids, producing large responses to CSM. We hypothesized that simulation of sternocleidomastoid "denervation" using pharmacological blockade would increase cardiovascular responses to CSM. Thirteen participants received supine and tilted CSM prior to intramuscular injections (6-8 mL distributed over four sites) of 2% lidocaine hydrochloride, and 0.9% saline (placebo) in contralateral sternocleidomastoid muscles. Muscle activation was recorded with electromyography (EMG) during maximal unilateral sternocleidomastoid contraction both pre- and postinjection. Supine and tilted CSM were repeated following injections and responses compared to preinjection. Following lidocaine injection, the muscle activation fell to 23 ± 0.04% of the preinjection value (P < 0.001), confirming neural block of the sternocleidomastoid muscles. Cardiac (RRI, RR interval), forearm vascular resistance (FVR), and systolic arterial pressure (SAP) responses to CSM did not increase after lidocaine injection in either supine or tilted positions (supine: ΔRRI -72 ± 31 ms, ΔSAP +2 ± 1 mmHg, ΔFVR +4 ± 4%; tilted: ΔRRI -20 ± 13 ms, ΔSAP +2 ± 2 mmHg, ΔFVR +2 ± 4%; all P > 0.05). Neural block of the sternocleidomastoid muscles does not increase cardiovascular responses to CSM. The pathophysiology of CSH remains unknown.

[Baroreceptor activation therapy for therapy-resistant hypertension: indications and patient selection : Recommendations of the BAT consensus group 2017]. / Barorezeptorakivierungstherapie bei therapierefraktärer Hypertonie: Indikation und Patientenselektion : Empfehlungen der BAT-Konsensusgruppe 2017.

Baroreceptor activation therapy (BAT) has been available for several years for treatment of therapy-refractory hypertension (trHTN). This procedure is currently being carried out in a limited number of centers in Germany, also with the aim of offering a high level of expertise through sufficient experience; however, a growing number of patients who are treated with BAT experience problems that treating physicians are confronted with in routine medical practice. In order to address these problems, a consensus conference was held with experts in the field of trHTN in November 2016, which summarizes the current evidence and experience as well as the problem areas in handling BAT patients.

[A severe stroke following carotid sinus massage]. / Een ernstig herseninfarct na carotismassage.

BACKGROUND: Carotid sinus massage is a widely used method for diagnosis and treatment of supraventricular tachycardia and carotid sinus hypersensitivity. Complications, mostly neurological, can occur but are rare. Carotid stenosis is a risk factor for complications. Hearing a carotid bruit on auscultation indicates stenosis, and is a contraindication for performing carotid sinus massage. However, the sensitivity of auscultation is insufficient. CASE DESCRIPTION: A 71-year-old man with a history of hypertension and hypercholesterolemia presented to the cardiology accident and emergency department with palpitations. A supraventricular tachycardia was found on examination, for which carotid sinus massage was performed. The patient developed severe aphasia and right-sided hemiparesis caused by an extensive stroke, and died a few days later. CONCLUSION: The chance of complications following carotid sinus massage is slight; however, this type of complication can have severe consequences. Safer alternative methods may be used for patients with supraventricular tachycardia. In older patients with vascular risk factors, more extensive diagnostic investigations for carotid stenosis should be considered in the diagnostic workup for carotid sinus hypersensitivity.

Hemodynamic responses to magnetic stimulation of carotid sinus in normotensive rabbits.

OBJECTIVES: Carotid baroreflex plays a crucial role in regulating arterial pressure. Based on this knowledge, electrical stimulation of carotid sinus was designed for treating resistant hypertension. However, the clinical implication of electrical stimulation of carotid sinus is largely restrained due to obvious invasiveness. This study aimed to evaluate the efficacy of magnetic stimulation of carotid sinus (MSCS), a noninvasive strategy, for lowering blood pressure in rabbits. METHODS: MSCS with graded intensities and frequencies were systematically attempted in normotensive rabbits. Blood pressure was recorded dynamically. Sinoaortic denervation and plasma hormone level analyses were performed. RESULTS: When the right carotid sinus was stimulated at 1 Hz frequency, a dose-effect relationship was observed between stimulation intensity (100-250% motor threshold) and mean arterial pressure (MAP) decrement (3.6 ±â€Š1.0 to 10.4 ±â€Š2.3 mmHg). When stimulation intensity was fixed at 200% motor threshold, the median reduction of MAP in 1-Hz group [10.8 (8.6-14.9) mmHg] was significantly higher than that in other frequency groups (all P < 0.05). Heart rates declined transiently after the initiation of MSCS. Compared with baseline (33.9 ±â€Š5.5 pg/ml), plasma epinephrine level increased during MSCS (88.1 ±â€Š9.6, P = 0.002). After ipsilateral sinoaortic denervation, MAP decrement (7.0 ±â€Š0.8 mmHg) was remarkably blunted compared with that in sham animals (13.0 ±â€Š1.1 mmHg, P = 0.001). CONCLUSION: The current study demonstrated that MSCS treatment can lower the arterial pressure in normotensive rabbits. This preliminarily result warrants further studies to establish the efficacy of MSCS in treating refractory hypertension.

Resistant Hypertension.

Conservatively, ten million people in the USA alone may suffer from RH and may be similarly prevalent elsewhere. Given the strong linear correlation between hypertension and cardiovascular outcomes, better control is paramount. We favor a multi-pronged approach. It may not suffice to address this by pharmacologic means only. Careful attention to modifiable risk factors, particularly sodium intake, adhering to a proper diet (i.e. DASH), and avoiding agents, i.e. non-steroidals, that can elevate the blood pressure, is key. Frequent follow up to establish the right treatment regimen and home blood pressuring monitoring can have a strong impact on control. Finally, consideration of device therapy may be a more viable option in the future.

Safety and tolerability of Tilt Testing and Carotid Sinus Massage in the octogenarians.

OBJECTIVE: to evaluate the safety and tolerability of Tilt Testing (TT) and Carotid Sinus Massage (CSM) in octogenarians with unexplained syncope. METHODS: patients consecutively referred for transient loss of consciousness to the 'Syncope Units' of three hospitals were enrolled. TT and CSM were performed according to the European Society of Cardiology guidelines on syncope. Complications were evaluated in each group. An early interruption of TT was defined as 'intolerance' and considered as a non-diagnostic response. RESULTS: one thousand four hundred and one patients were enrolled (mean age 72 ± 16 years, male 40.8%). Six hundred and ninety-four patients (49.5%) were 80 years old or older (mean age 83 ± 3 years) and 707 (50.5%) were younger (mean age 60 ± 17 years). Complications after TT occurred in 4.5% of older patients and in 2.1% of the younger ones (P = 0.01). All complications were 'minor/moderate', as prolonged hypotension, observed in ∼3% of patients ≥80 years. Major complications such as sustained ventricular tachycardia, ventricular fibrillation, asystole requiring cardiac massage, transient ischaemic attack, stroke and death were not observed in any patient. The presence of orthostatic hypotension and the mean number of syncopal episodes were predictors of TT complications. Intolerance was reported in 2.4% of older patients and 1% of the younger ones (P = 0.08), mainly due to orthostatic intolerance. No complications occurred after CSM. CONCLUSIONS: TT and CSM appear to be safe and well tolerated in octogenarians, who should not be excluded by age from the diagnostic work-up of syncope.

Acute on/off effects and chronic blood pressure reduction after long-term baroreflex activation therapy in resistant hypertension.

BACKGROUND: Baroreflex activation therapy (BAT) by electrical stimulation of baroreceptors at the carotid sinus is a promising therapeutic approach to reduce elevated blood pressure (BP). To assess the efficacy of long-term BAT, we investigated acute BP alterations after device deactivation and reactivation (on/off effects) in patients on chronic BAT, as well as chronic BP reductions. METHOD: Resistant hypertension patients (n = 17) were enrolled in an open-label, single-arm evaluation of unilateral BAT after exclusion of secondary hypertension. Initial eligibility criteria were SBP≥  140 mmHg, despite stable medical therapy with at least three antihypertensive drugs including at least one diuretic. For on/off testing, several office cuff BP measurements were performed: at rest with activated device, 4-6 min after deactivation, and 4-6 min after reactivation. RESULTS: Before BAT, mean office cuff BP was 179 ±â€Š25 over 98 ±â€Š18 mmHg. At the time of on/off testing (15.1 ±â€Š8.7 months after initial activation and before deactivation), BP was reduced to 147 ±â€Š29 over 84 ±â€Š20 mmHg. On deactivation, SBP increased to 158 ±â€Š38 mmHg (P = 0.004) and DBP to 89 ±â€Š23 mmHg (P = 0.04). After reactivation, SBP decreased to 144 ±â€Š34 mmHg (P = 0.002 vs. deactivation) and DBP to 83 ±â€Š23 mmHg (P = 0.009). There was no correlation between duration of chronic BAT and systolic or diastolic acute on/off response. CONCLUSION: Unilateral BAT reduces BP in patients with resistant hypertension in the long term. There is a significant on/off effect on BP, supporting the efficacy of BAT. The acute on/off response to BAT does not depend on treatment duration. Thus, no evidence of tolerance over time to chronic BAT was found.

[The role of cardiac pacing therapy in the management of carotid sinus syndrome].

INTRODUCTION: Carotid sinus syndrome is characterized by a hypersensitive carotid sinus and syncope. Although we have clear guidelines for the diagnosis and treatment of carotid sinus syndrome, the efficacy of pacing therapy with this indication has not been the subject of many studies. OBJECTIVE: This study aimed to assess the efficacy and safety of pacing therapy in the treatment of patients with carotid sinus syndrome and to determine the factors contributing to symp- toms recurrence after pacemaker implantation. METHODS: This study was retrospective and included 32 patients in whom a pacemaker was implanted due to carotid sinus syn- drome at the Pacemaker Center, Clinical Center of Serbia, be- tween April 2005 and April 2012. Carotid sinus massage and head-up tilt test (HUTT) were performed to select patients with cardioinhibitory and mixed type carotid sinus syndrome, who were enrolled to the study. RESULTS: The mean age of patients was 65.6 ± 11.5 years and 20 (62.5%) were men. The mean follow-up period was 4.3 ± 1.9 years. HUTT was performed in 3 (9.4%) patients. Twenty-seven (84.4%) patients presented with cardioinhibitory and 5 (15.6%) with mixed type of carotid sinus syndrome. After pacemaker implantation, 22 (68.7%) patients had no further symptoms, 8 (25.0%) had syncope and 2 (6.3%) presyncope.The mixed type of the disease (HR 3.1; 95% CI 1.4-5.1; p = 0.021) and implanta- tion of pacemaker in WI mode (HR 1.8; 95% CI 1.1-3.2; p = 0.034) were independent predictors of symptoms recurrence. There were 3 (9.4%) perioperative surgical complications. CONCLUSION: Pacemaker therapy is an effective and safe treat- ment for patients with carotid sinus syndrome. As predictors of symptoms persistence after pacemaker implantation in our population, we identified the implantation of pacemaker in WI mode and the mixed type of carotid sinus syndrome.

Reconsidering the effectiveness and safety of carotid sinus massage as a therapeutic intervention in patients with supraventricular tachycardia.

OBJECTIVE: The objectives of our investigation were to review the evidence for the efficacy and safety of carotid sinus massage in terminating supraventricular tachycardia and to determine if other potentially less harmful interventions have been established to be safer and more effective. METHODS: A search using PubMed, Ovid, and COCHRANE databases was performed using the terms supraventricular tachycardia, carotid sinus massage, SVT, and CSM. Articles not written in English were excluded. There was a paucity of randomized controlled trials comparing various supraventricular tachycardia (SVT) interventions. However, articles of highest quality were selected for review and inclusion. In addition, articles examining potential hazards of carotid sinus massage in case report format were reviewed, even when performed for other indications other than SVT, as the maneuver is identically performed. Selected articles were reviewed by both authors for relevance to the topic. RESULTS: Summarizing the findings of this review leads to these 3 fundamental conclusions. First, a therapeutic intervention should only be performed when the benefit of the procedure outweighs its risk. Carotid sinus massage exposes the patient to rare but potentially devastating iatrogenic harm. Second, a therapeutic intervention should be efficacious. The efficacy of carotid sinus massage in terminating supraventricular tachycardia appears to be modest at best. Third, other readily available, easily mastered, and potentially safer and more efficacious alternative interventions are available such as Valsalva maneuver and pharmacologic therapy. CONCLUSION: Based on the limited evidence available, we believe that carotid sinus massage should be reconsidered as a first-line therapeutic intervention in the termination of SVT.

The future of interventional management of hypertension: threats and opportunities.

In about 48% hypertensive patients in the United States, blood pressure remains higher than accepted treatment targets despite broad availability of effective pharmaceutical agents. Of these 48%, recent estimates define about 10-11% have treatment-resistant hypertension (TR-HTN). Compensatory changes in sympathetic nervous system function are an important component of HTN. Recent technical advances targeting the sympathetic activity of the carotid sinuses (Baroreflex Activation Therapy-BAT) and the renal sympathetic nerves (Renal Denervation Therapy-RDT) have renewed interest in invasive therapy for the treatment of drug-resistant hypertension. Encouraging results from the recent Rheos Pivotal and Symplicity HTN-2 trials on the safety and efficacy of BAT and RDT respectively, indicate that invasive approaches can safely reduce blood pressure in patients with resistant hypertension. The main goal of this article is to review the results of preclinical and clinical studies on the electric stimulation of the carotid sinus and the catheter-based renal denervation.

Renal and cardiac effects of renal sympathetic denervation and carotid baroreceptor stimulation.

Cumulative evidence nowadays supports the dominant role of sympathetic nervous system (SNS) activation in patients with hypertension, congestive heart failure, and renal dysfunction. During the last years innovative interventional treatments [renal sympathetic denervation (RSD) and baroreflex activation therapy (BAT)] have emerged and accompanied by sustained reductions of blood pressure (BP) levels. Moreover, these promising therapies are favorable not only on BP regulation but also on the SNS overdrive-related organ damage. The present review focuses on the association of SNS activation with renal and cardiac diseases and presents the cardiorenal effects of RSD and BAT in experimental and clinical settings.

The pathophysiological basis of carotid baroreceptor stimulation for the treatment of resistant hypertension.

The prevalence of resistant hypertension and existing limitations in antihypertensive drug therapy renders the interventional management of hypertension an attractive alternative. Carotid baroreceptors have been traditionally thought to be implicated only in short-term blood pressure regulation; however recent evidence suggests that the baroreceptors might play an important role even in the long-term blood pressure regulation. Electrical baroreflex stimulation appears safe and effective and might represent a useful adjunct to medical therapy in patients with resistant hypertension. This review endeavors to summarize the complex pathophysiology of blood pressure regulation, to describe the baroreflex circuit, its anatomy and physiology, to present previous data refuting a role for the baroreceptors in the long-term control of blood pressure and recent animal and human data suggesting an effective role of carotid baroreceptor activation in long-lasting blood pressure reduction. In this paper we attempt to critically evaluate existing information in this area and provide the scientific basis for carotid baroreceptor stimulation in the management of resistant hypertension.