Carotid Sinus Stimulation: Background, Technique, and Future Directions

History

The history of device-based therapy for hypertension has been summarized recently. As early as 1958, it was reported that electrical stimulation of the carotid sinus nerve in normotensive dogs produced an acute decrease in BP, and similar findings were reported in several animal models of hypertension shortly thereafter. Following the original animal model report, it was demonstrated that direct electrical stimulation of the carotid sinus in humans (undergoing neck dissection for cancer) had the same results.

These findings led to more thorough investigation in humans. A single case was reported in 1966 of a 40-year-old man with a BP of 260/165 mm Hg despite four medications. Bilateral stimulation (2.5 V) produced a sustained drop in pressure to 150/90 mm Hg. The device consisted of electrodes at the sinuses connected to a generator placed beneath the pectoralis muscle. The leads were subcutaneously tunneled, and the generator could be turned on or off by placing a magnet over the device, but no further modification could be performed. The first series was reported in 1967 by Seymour Schwartz; he described a mean decrease in BP of 48 mm Hg in eight patients, six of whom reduced their BP medications. Further clinical benefit was demonstrated by at least one other group around this time. Unfortunately this treatment came at the wrong time. Most setups at this time required external power sources and communication and were therefore bulky and impractical for long-term use. In addition, pharmacologic therapy dramatically improved in this era, making the problem less acute. As a result, this concept was essentially forgotten for the remainder of the century.

This phenomenon was reevaluated largely through a large body of work by Thomas Lohmeier, a physiologist at the University of Mississippi. In a large series of animal experiments, he was able to reconfirm that this effect was real and reproducible, was effective in normotensive as well as hypertensive (sodium-loaded and obesity models) canines, and, most importantly, was sustainable ( Fig. 66.5 ). This work led to the formation of a company (CVRx, Inc., Minneapolis, MN) whose sole aim was to resurrect this concept using 21st-century technology. A number of trials have demonstrated the efficacy of carotid sinus stimulation in both hypertension and in heart failure, and a second-generation, low-profile device (Barostim neo , CVRx, Inc.) has been approved for use in Europe.

Device-Based Therapy in Hypertension Trial

The Device-Based Therapy in Hypertension Trial (DEBuT-HT) was the initial controlled feasibility trial of the commercially available, clinically practical device. Patients with resistant hypertension (SBP >160 mm Hg despite three medications, one of which included a diuretic) underwent bilateral carotid sinus exposure and lead placement. Electrodes were tunneled subcutaneously and attached to a pulse generator implanted in the chest wall ( Fig. 66.6 ). A total of 45 patients were enrolled in this trial, which was performed in Europe starting in 2006. Results on 18 patients after 4 years of therapy were presented in 2010 at the 20th annual meeting of the European Society of Hypertension in Oslo, Norway, and published in abstract form. BP response was sustained, and mean reductions were impressive: 53 ± 9 mm Hg in SBP, 30 ± 6 mm Hg in diastolic pressure, and 5 ± 2 beats per minute in heart rate ( Fig. 66.7 ). Encouragingly, patients were able to decrease their antihypertensive medications by approximately one-third (5 ± 1.3 medications at onset to 3.4 ± 1 medications at 4 years).