AimsHeart failure (HF) pathophysiology is believed to be mediated by autonomic dysfunction, including chronic sympathoexcitation and diminished baroreflex sensitivity, which correlate with mortality risk. Baroreflex activation therapy (BAT) is a device-based treatment providing chronic baroreflex activation through electrical stimulation of the carotid sinus. BAT chronically reduces sympathetic activity in resistant hypertension. The purpose of this investigation is to determine BAT effects in clinical HF.Methods and resultsIn a single-centre, open-label evaluation, patients with NYHA class III HF, EF <40%, optimized medical therapy, and ineligible for cardiac resynchronization received BAT for 6 months. Efficacy was assessed with serial measurement of muscle sympathetic nerve activity (MSNA) and clinical measures of quality of life and functional capacity. Eleven patients participated in the trial. MSNA was reduced over 6 months from 45.1 ± 7.7 to 31.3 ± 8.3 bursts/min and from 67.6 ± 12.7 to 45.1 ± 11.6 bursts/100 heartbeats, decreases of 31% and 33%, respectively (P < 0.01). Concomitant improvements occurred in baroreflex sensitivity, EF, NYHA class, quality of life and 6 min hall walk (6MHW) distance (P ≤ 0.05 each). On an observational basis, hospitalization and emergency department visits for worsening HF were markedly reduced. One complication, perioperative anaemia requiring transfusion, occurred during the study.ConclusionBAT was safe and provided chronic improvement in MSNA and clinical variables. Based on present understanding of HF pathophysiology, these results suggest that BAT may improve outcome in HF by modulating autonomic balance. Prospective, randomized trials to test the hypothesis are warranted.

Obese persons are at increased cardiovascular risk and exhibit increased arterial stiffness and impaired endothelial function of large‐ and medium‐size arteries. We hypothesized that normotensive subjects suffering from severe obesity would also present remodeling and endothelial dysfunction of small resistance arteries. A total of 16 lean (age: 49.6 ± 2.9 years, BMI: 22.9 ± 0.3 kg/m2, mean ± s.e.m.) and 17 age‐matched severely obese (BMI: 41.1 ± 2.3 kg/m2) normotensive subjects were investigated. None had glucose or lipid metabolic abnormalities except for insulin resistance. Resistance arteries, dissected from abdominal subcutaneous tissue, were assessed on a pressurized myograph. For superimposable blood pressure, the media thickness, media cross‐sectional area (CSA), and media‐to‐lumen ratio values of resistance arteries were markedly and significantly greater in obese compared to lean subjects (media thickness 26.3 ± 0.6 vs. 16.2 ± 0.6 µm, CSA 22,272 ± 1,339 vs. 15,183 ± 1,186 µm2, and media‐to‐lumen ratio 0.113 ± 0.006 vs. 0.059 ± 0.001, respectively, P < 0.01). Acetylcholine‐induced relaxation was impaired in vessels from obese subjects compared to the lean individuals (−40.4 ± 1.3%, P < 0.01), whereas endothelium‐independent vasorelaxation was similar in all groups. Stiffness of small arteries as assessed by the stress/strain relationship was similar in lean and severely obese subjects. We conclude that severe human obesity is associated with profound alterations in structural and functional characteristics of small arteries, which may be responsible for the presence of elevated cardiovascular risk and increased incidence of coronary, cerebrovascular and renal events reported in obesity.

Abstract-The prognostic value of white coat hypertension (WCH) is still debated. In 2051 subjects representative of the general population of Monza, we measured office, ambulatory, and home blood pressure (BP). The risk of cardiovascular and allcause mortality was assessed over 16 years in normotensive, sustained hypertensive, and WCH subjects, the last group being defined as usually done in clinical practice (ie, by normality of 1 out-of-office [ambulatory or home] BP with an office BP elevation). Compared with normotensive subjects, the risk of cardiovascular mortality, as adjusted for potential confounders, showed a progressive significant increase in WCH and sustained hypertensive subjects (2.04 and 2.94; P=0.006). In either group, a significant increase in adjusted risk was also seen for all-cause mortality. However, when the WCH group was subdivided into 2 subgroups, that is, subjects in whom both out-of-office BPs were normal (true WCH, 42%) or one BP was normal whereas the other was elevated (partial WCH, 58%), only the latter showed a significantly greater adjusted risk of cardiovascular and all-cause mortality (2.76 and 1.58; P<0.03). Compared with normotensive subjects, the partial WCH group also exhibited a marked increase in adjusted risk of developing sustained hypertension over a 10-year time period (2.58; P<0.0001), but in this case the risk was also increased in true WCH subjects (2.89; P<0.0001). Thus, WCH includes subjects with a widely different long-term risk of a cardiovascular event. To identify those at higher risk, measurements of