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  • Review Article
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Carotid baroreflex activation therapy for resistant hypertension

Nature Reviews Cardiology volume 12, pages 451–463 (2015)Cite this article

Subjects

Key Points

  • Arterial baroreceptors are pressure-sensitive nerve endings in the walls of the carotid sinuses and aortic arch that sense the increases and decreases in blood pressure

  • Resistant hypertension is accompanied by sympathetic overactivity and partial attenuation of arterial baroreflex function, caused largely by stiffening of the great vessels in which the baroreceptor nerve endings are embedded

  • Electrical field stimulation of the carotid baroreceptor axons (carotid baroreflex activation therapy) has been shown to mediate acute reductions in sympathetic activity and blood pressure in patients with resistant hypertension

  • In an initial phase III trial on continuous carotid baroreflex activation therapy for resistant hypertension, the prototype implantable device was associated with equivocal efficacy and surgically-induced facial nerve palsy

  • In subsequent phase I and IIa trials with a miniaturized second-generation system, unilateral carotid stimulation produced reductions in blood pressure equivalent to bilateral stimulation, with no major adverse events

  • A new phase III trial for the use of this second-generation system for resistant hypertension has been registered

Abstract

Arterial baroreceptors are mechanosensitive sensory nerve endings in the walls of the carotid sinuses and aortic arch that buffer the increases and decreases in arterial blood pressure. Electrical field stimulation of the carotid sinus, known as carotid baroreflex activation therapy, holds promise as a novel device-based intervention to supplement, but not replace, drug therapy for patients with resistant hypertension. Acute electrical field stimulation of even one carotid sinus can cause a sufficiently large reflex decrease in blood pressure to overcome offsetting reflexes from the contralateral carotid baroreceptors and aortic baroreceptors that are not paced. However, the initial phase III Rheos Pivotal Trial on continuous carotid baroreceptor pacing for resistant hypertension with the first-generation baroreceptor pacemaker yielded equivocal data on efficacy and adverse effects due to facial nerve injury during surgical implantation. A miniaturized second-generation pacing electrode has seemingly overcome the safety issue, and early results with the new device suggest efficacy of unilateral carotid sinus stimulation in heart failure. A phase III trial of this new device for resistant hypertension has been registered.

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Figure 1: An historical perspective on our understanding of baroreceptor physiology.
Figure 2: Sympathetic neural mechanisms of blood pressure regulation and treatment target of carotid baroreceptor pacing, as well as renal denervation.
Figure 3
Figure 4: The mechanical component of carotid baroreflex deactivation is blocked by local application of catecholamines to the carotid sinus in dogs.
Figure 5: Arterial baroreflex failure.
Figure 6: Chest roentgenogram after implantation showing the Rheos® system (CVRx, Inc., USA) electrodes placed around both carotid sinuses (arrow).
Figure 7: Management of a hypertensive crisis with baroreflex activation therapy.
Figure 8: Responses of ABP, HR, and MSNA to the onset and offset of electrical field stimulation of the carotid sinus with the Rheos® system (CVRx, Inc., USA).
Figure 9: Results from the Rheos® system (CVRx, Inc., USA) trials.

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  1. The Cedars–Sinai Hypertension Centre, The Heart Institute, Cedars–Sinai Medical Centre, 127 South San Vicente Boulevard, Suite A9111, Los Angeles, 90048, CA, USA

    Ronald G. Victor

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Correspondence to Ronald G. Victor.

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R.V. declares that he is an Advisory Board member for Medtronic, Northwind, and TrophyNOD.

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Victor, R. Carotid baroreflex activation therapy for resistant hypertension. Nat Rev Cardiol 12, 451–463 (2015). https://doi.org/10.1038/nrcardio.2015.96

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