Research ArticleMinimally invasive system for baroreflex activation therapy chronically lowers blood pressure with pacemaker-like safety profile: results from the Barostim neo trial
Introduction
Despite advances in treatment, hypertension (HTN) persists as a significant public health problem in terms of patient morbidity/mortality and cost to the health care system, impacting more than 76 million Americans with estimated direct and indirect costs in 2008 totaling over $50 billion.1 The toll is especially heavy for resistant HTN, in which conventional therapies do not provide adequate control.2, 3 Resistant HTN is formally defined as failure to achieve office cuff blood pressure (BP) at or below 140/90 mm Hg (130/80 mm Hg in patients with chronic kidney disease and/or diabetes) while receiving treatment with maximally tolerated doses of three antihypertensive medications, of which one is a diuretic. Prevalence of resistant HTN is expected to continue to rise because of an aging population and increased prevalence of obesity, sleep apnea, and chronic kidney disease.4
Baroreflex activation therapy (BAT) is an alternative treatment option for resistant HTN that modulates the autonomic nervous system to restore sympathovagal balance, thereby reducing arterial resistance and stiffness while increasing venous capacitance and renal natriuresis. The net effect is to maintain tissue perfusion at reduced arterial pressures while relocating excess volume away from the central compartment.5 To date, BAT is the only treatment for resistant HTN that has demonstrated long-term safety and efficacy in a large-scale, double blind, randomized, controlled trial.6 However, shortcomings in trial design and safety benchmarks contributed to the first-generation Rheos system not achieving prespecified endpoints for short-term safety and efficacy. To address these limitations, a second-generation system has been developed as a new, minimally invasive approach for administering BAT.
The purpose of this investigation is to measure the safety and efficacy profile of this new advancement for BAT in resistant hypertensive patients over a 6-month period, with the objective of verifying that it is suitable for demonstrating short- and long-term safety and efficacy in randomized, controlled trials.
Section snippets
System for Delivering BAT
BAT was delivered using the Barostim neo™ system, a second-generation system comprised of a pulse generator and a lead similar to a contemporary pacemaker system (Figure 1) and controlled with a laptop computer-based programming system via radiofrequency telemetry. The pulse generator is implanted unilaterally in the pectoral region ipsilateral to the stimulated carotid sinus. The electrode portion of the lead consists of a single platinum-iridium disc coated with iridium oxide attached
Results
Thirty patients (29 EU, 1 Canada) were implanted at seven centers (6 EU, 1 Canada) between February and June 2011. Baseline characteristics and medications are reported in Table 1. The population was evenly divided between male and female patients who were generally middle-aged, obese, and under intensive treatment for resistant HTN (average 6.1 ± 2.7 medications). Only 1 patient was not taking diuretics because of intolerance. Before enrollment, 6 patients had undergone renal nerve ablation in
Discussion
A second-generation, minimally invasive system for BAT led to substantial systolic BP reductions, averaging 26 mm Hg at 6 months, that are comparable to the 21 mm Hg and 26 mm Hg reductions in the DEBuT trial at 3 months9 and Rheos Pivotal Trial at 6 months,6 respectively. Furthermore, 43% of the resistant hypertensive patients achieved systolic BPs <140 mm Hg by 6 months of therapy. Presuming that the long-term course observed in earlier trials applies to these patients, it would be expected
Acknowledgments
The authors acknowledge the following for their contributions to this investigation: Navid Madershahian, MD (University of Cologne, Cologne, Germany); Dieter Zenker, MD (University of Göttingen, Göttingen, Germany); Gert Hennig, MD (Hospital St. Georg, Leipzig, Germany); Oliver Vonend, MD, and Atilla Sagban, MD (University Hospital Düsseldorf, Düsseldorf, Germany); Jan J. M. Tordoir, MD, PhD, and Teba Alnima, MD (University Hospital Maastricht and CARIM, Maastricht, The Netherlands); John H.
References (23)
- et al.
Resistant hypertension, secondary hypertension, and hypertensive crises: diagnostic evaluation and treatment
Cardiol Clin
(2010) - et al.
Resistant hypertension: an overview of evaluation and treatment
J Am Coll Cardiol
(2008) - et al.
Chronic baroreflex activation: a potential therapeutic approach to heart failure with preserved ejection fraction
J Card Fail
(2011) - et al.
Baroreflex activation therapy lowers blood pressure in patients with resistant hypertension: results from the double-blind, randomized, placebo-controlled Rheos Pivotal Trial
J Am Coll Cardiol
(2011) - et al.
An implantable carotid sinus baroreflex activating system: surgical technique and short-term outcome from a multi-center feasibility trial for the treatment of resistant hypertension
Eur J Vasc Endovasc Surg
(2007) - et al.
Novel baroreflex activation therapy in resistant hypertension: results of a European multi-center feasibility study
J Am Coll Cardiol
(2010) - et al.
A selective endothelin-receptor antagonist to reduce blood pressure in patients with treatment-resistant hypertension: a randomised, double-blind, placebo-controlled trial
Lancet
(2009) Renal sympathetic denervation for refractory hypertension
Lancet
(2011)- et al.
Renal sympathetic denervation: the jury is still out
Lancet
(2010) - et al.
Heart disease and stroke statistics—2012 update: a report from the American Heart Association
Circulation
(2012)
Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research
Circulation
Cited by (236)
Device's design and clinical perspectives for resistant hypertension therapy
2024, International Journal of Cardiology: Cardiovascular Risk and PreventionRole of splanchnic circulation in the pathogenesis of heart failure: State-of-the-art review
2024, Journal of CardiologyMedical Management and Device-Based Therapies in Chronic Heart Failure
2023, Journal of the Society for Cardiovascular Angiography and InterventionsManagement of Heart Failure With Reduced Ejection Fraction
2023, Current Problems in CardiologyRenal sympathetic activity: A key modulator of pressure natriuresis in hypertension
2023, Biochemical PharmacologyDevice Therapies for Hypertension
2023, Hypertension: A Companion to Braunwald's Heart Disease
Drs. Hoppe, Brandt, Wachter, Beige, Rump, Kroon, and Haller have received research grant support from CVRx and are presently paid consultants or advisors of CVRx, Inc. Drs. Cates and Lovett are employees of CVRx, Inc.