586 Hypertension March 2016 elicits acute reductions in sympathetic vasoconstrictor tone and BP in patients with treatment-resistant hypertension . Methods Patients

Devices reducing blood pressure (BP) through stimulation of afferent baroreflex nerves have been developed decades ago but failed mainly for technical reasons. More recently, implantable devices electrically stimulating the carotid sinus have been developed and clinically tested in patients with severe treatment-resistant hypertension. The first-generation device (Rheos) applied bilateral localized field stimulation through bipolar electrodes in tripolar configuration placed around the carotid sinuses. In carefully conducted animal experiments and an uncontrolled clinical trial on resistant hypertension, the treatment lowered BP. A mechanistic substudy showed that BP reduction was mediated through sympathetic inhibition and that normal baroreflex regulation remained intact with carotid sinus stimulation. In the controlled phase of a subsequent clinical trial, electric carotid sinus stimulation lowered BP; however, the predefined end point acute efficacy defined as proportion of ≥10 mm Hg systolic BP (SBP) responders was not significantly different between groups. The second-generation device (neo), which is approved and clinically applied in Europe, uses a small unilateral unipolar disk electrode to decrease invasiveness and to improve battery life. Patients with resistant arterial hypertension implanted with the new device showed BP reductions in an uncontrolled clinical trial. A controlled clinical trial is currently ongoing in the United States (NCT01679132). Electric fields produced by disk-shaped unipolar electrodes differ markedly from electric fields produced by bipolar circumferential electrodes, which together with modified stimulation settings could affect the efficacy in engaging carotid baroreceptors. The side-effect profile attributable to electric stimulation of surrounding anatomic structures could also differ between unipolar and bipolar electrode designs. Therefore, we tested the hypothesis that unilateral unipolar carotid sinus stimulation Abstract—Bilateral bipolar electric carotid sinus stimulation acutely reduced muscle sympathetic nerve activity (MSNA) and blood pressure (BP) in patients with resistant arterial hypertension but is no longer available. The second-generation device uses a smaller unilateral unipolar disk electrode to reduce invasiveness while saving battery life. We hypothesized that the second-generation device acutely lowers BP and MSNA in treatment-resistant hypertensive patients. Eighteen treatmentresistant hypertensive patients (9 women/9 men; 53±11 years; 33±5 kg/m) on stable medications have been included in the study. We monitored finger and brachial BP, heart rate, and MSNA. Without stimulation, BP was 165±31/91±18 mm Hg, heart rate was 75±17 bpm, and MSNA was 48±14 bursts per minute. Acute stimulation with intensities producing side effects that were tolerable in the short term elicited interindividually variable changes in systolic BP (–16.9±15.0 mm Hg; range, 0.0 to −40.8 mm Hg; P=0.002), heart rate (−3.6±3.6 bpm; P=0.004), and MSNA (−2.0±5.8 bursts per minute; P=0.375). Stimulation intensities had to be lowered in 12 patients to avoid side effects at the expense of efficacy (systolic BP, −6.3±7.0 mm Hg; range, 2.8 to −14.5 mm Hg; P=0.028 and heart rate, −1.5±2.3 bpm; P=0.078; comparison against responses with side effects). Reductions in diastolic BP and MSNA (total activity) were correlated (r=0.329; P=0.025). In our patient cohort, unilateral unipolar electric baroreflex stimulation acutely lowered BP. However, side effects may limit efficacy. The approach should be tested in a controlled comparative study. (Hypertension. 2016;67:585-591. DOI: 10.1161/HYPERTENSIONAHA.115.06486.) • Online Data Supplement