Eric G. Lovett

Baroreflex Activation Therapy provides durable benefit in patients with resistant hypertension: results of long-term follow-up in the Rheos Pivotal Trial

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.

Minimally invasive system for baroreflex activation therapy chronically lowers blood pressure with pacemaker-like safety profile: results from the Barostim neo trial

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.

Baroreflex activation therapy for the treatment of heart failure with a reduced ejection fraction: safety and efficacy in patients with and without cardiac resynchronization therapy

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.

Bilateral or Unilateral Stimulation for Baroreflex Activation Therapy

Abstract—Previous trials have shown that in patients with resistant hypertension device-based baroreflex activation therapy (BAT) can substantially reduce blood pressure. However, the fact that electrodes had to be implanted bilaterally may be a drawback for further development of the technique. In this study, we explored whether unilateral stimulation would produce comparable results as bilateral stimulation. In the Pivotal trial, treatment-resistant hypertensive patients were randomized to receive either immediate BAT or deferred BAT, that is, 6 months after implantation. We adjusted stimulation parameters individually so as to provide optimal baroreflex activation. Unilateral stimulation was applied unless bilateral stimulation resulted in a greater blood pressure reduction. When we pooled the 6-month data for the group with immediate BAT and the 12-month data for the group with deferred BAT, a total of 215 patients had been stimulated on one side only (127 at the right side and 88 at the left side), whereas 80 patients had been stimulated bilaterally. Although blood pressure and heart rate did not differ between the 2 groups at baseline, all these variables were significantly lower in the unilateral than in the bilateral group after the 6-month period. When we compared the effect of right-sided stimulation with those of either left-sided or bilateral stimulation, we found right-sided stimulation to be the most effective. We conclude that unilateral and in particular right-sided BAT has a more profound effect on blood pressure than bilateral or left-sided BAT. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00442286.

Chronic baroreflex activation by the Rheos ® system: An overview of results from european and North American feasibility studies

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.

Effects of electrical stimulation of the carotid sinus baroreflex using the Rheos® device on ventricular-vascular coupling and myocardial efficiency assessed by pressure-volume relations in non-vagotomized anesthetized dogs

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® 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.

Surgical Experience and Long-term Results of Baroreflex Activation Therapy for Heart Failure With Reduced Ejection Fraction

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.

8B.06: BAROREFLEX ACTIVATION THERAPY CONSISTENTLY MAINTAINS BLOOD PRESSURE REDUCTION IN A LARGE RESISTANT HYPERTENSION COHORT FOR AT LEAST 6 YEARS.

Objective: Previous reports have indicated that blood pressure (BP) reductions imparted by baroreflex activation therapy (BAT) in patients with resistant hypertension (rHTN) are maintained for at least 5 years. Because such reports have focused only on patients who remain active, it is possible that selection bias could overstate the impact of BAT. The purpose of this investigation is to comprehensively describe long-term BP reductions in rHTN patients receiving BAT using all data currently available. Design and method: Following collection of the pre-specified 12-month endpoints, patients were followed every 6 months. BP data were collected at each follow-up using a protocol-defined technique to minimize bias. Results: Original trial enrollment consisted of 322 patients. Of those, 182 presently remain active while 140 are inactive due to withdrawal from the study (112) or death (28). Consistent with earlier reports, BP reductions were > 30/15 mmHg for at least 6 years. Long-term therapy safety was excellent with low rates of stroke, myocardial infarction and hypertensive urgency. Figure. No caption available. Conclusions: BAT-induced BP reductions in rHTN patients were remarkably consistent over time, maintaining high levels of clinical and statistical significance. Previous reports of only active patients faithfully represent the true course of BP response to BAT in a large rHTN cohort.

BAROREFLEX ACTIVATION THERAPY IMPROVES NTPROBNP AND SIX-MINUTE WALK DISTANCE IN PATIENTS WITH SYMPTOMATIC HEART FAILURE

Baroreflex activation therapy (BAT) modulates sympathovagal balance, which is deranged in patients with heart failure leading to increased morbidity and mortality. Our aim was to study the effect of BAT on levels of the prognostic markers NTproBNP, NYHA class and 6-Minute Walk Test in patients with