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Background: Ultrasound and radiofrequency renal denervation (RDN) have been shown to safely lower blood pressure (BP) in hypertension., Aims: The TARGET BP OFF-MED trial investigated the efficacy and safety of alcohol-mediated renal denervation (RDN) in the absence of antihypertensive medications., Methods: This randomised, blinded, sham-controlled trial was conducted in 25 centres in Europe and the USA. Patients with a 24-hour systolic BP of 135-170 mmHg, an office systolic BP 140-180 mmHg and diastolic BP ≥90 mmHg on 0-2 antihypertensive medications were enrolled. The primary efficacy endpoint was the change in mean 24-hour systolic BP at 8 weeks. Safety endpoints included major adverse events up to 30 days., Results: A total of 106 patients were randomised; the baseline mean office BP following medication washout was 159.4/100.4±10.9/7.0 mmHg (RDN) and 160.1/98.3±11.0/6.1 mmHg (sham), respectively. At 8 weeks post-procedure, the mean (±standard deviation) 24-hour systolic BP change was â2.9±7.4 mmHg (p=0.009) versus â1.4±8.6 mmHg (p=0.25) in the RDN and sham groups, respectively (mean between-group difference: 1.5 mmHg; p=0.27). There were no differences in safety events between groups. After 12 months of blinded follow-up, with medication escalation, patients achieved similar office systolic BP (RDN: 147.9±18.5 mmHg; sham: 147.8±15.1 mmHg; p=0.68) with a significantly lower medication burden in the RDN group (mean daily defined dose: 1.5±1.5 vs 2.3±1.7; p=0.017)., Conclusions: In this trial, alcohol-mediated RDN was delivered safely but was not associated with significant BP differences between groups. Medication burden was lower in the RDN group up to 12 months.

Purpose: Baroreflex activation therapy (BAT) has been shown to lower blood pressure in patients with resistant hypertension. The purpose of this study was to analyze whether this translates into a reduction of more relevant clinical endpoints., Methods: Patients with resistant hypertension were treated with the second-generation BAT system. Records on hospitalization (dates of admission and discharge, main diagnosis) were obtained from medical insurance companies., Results: Records on hospitalization were available for a period of 1 year before BAT in two patients and 2 years in 22 patients. The total number of hospitalizations per patient was 3.3 ± 3.5/year before BAT and 2.2 ± 2.7/year after BAT (p = 0.03). Hospitalizations related to hypertension were significantly decreased from 1.5 ± 1.6/year before BAT to 0.5 ± 0.9/year after BAT (p < 0.01). The cumulative duration of hypertension-related hospital stays was significantly reduced from 8.0 ± 8.7 days/year before BAT to 1.8 ± 4.8 days/year after BAT (p < 0.01). Office cuff blood pressure was 183 ± 27 mmHg over 102 ± 17 mmHg under 6.6 ± 2.0 antihypertensive drugs before BAT and 157 ± 32 mmHg over 91 ± 20 mmHg (both p < 0.01) under 5.9 ± 1.9 antihypertensive drugs (p = 0.09 for number of drugs) at latest follow-up. Daytime ambulatory blood pressure was 164 ± 21 mmHg over 91 ± 14 mmHg before BAT and 153 ± 21 mmHg (p = 0.03) over 89 ± 15 mmHg (p = 0.56) at latest follow-up. Heart rate was 75 ± 16 bpm before BAT and 72 ± 12 bpm at latest follow-up (p = 0.35)., Conclusions: Rate and duration of hypertension-related hospitalizations in patients with severe resistant hypertension were lowered after BAT. Whether the response is mediated through improvements in blood pressure control requires further studies.

Arterial baroreflex activation through electrical carotid sinus stimulation has been developed for the treatment of resistant hypertension. Previous studies suggested that the peripheral chemoreflex is tonically active in hypertensive patients and may inhibit baroreflex responses. We hypothesized that peripheral chemoreflex activation attenuates baroreflex efficacy evoked by electrical carotid sinus stimulation. We screened 35 patients with an implanted electrical carotid sinus stimulator. Of those, 11 patients with consistent acute depressor response were selected (7 men/4 women, age: 67±8 years, body mass index: 31.6±5.2 kg/m 2 , 6±2 antihypertensive drug classes). We assessed responses to electrical baroreflex stimulation during normoxia, isocapnic hypoxia (SpO 2 : 79.0±1.5%), and hyperoxia (40% end-tidal O 2 fraction) by measuring heart rate, blood pressure, ventilation, oxygen saturation, end-tidal CO 2 and O 2 fractions, and muscle sympathetic nerve activity. During normoxia, baroreflex activation reduced systolic blood pressure from 164±27 to 151±25 mm Hg (mean±SD, P <0.001), heart rate from 64±13 to 61±13 bpm ( P =0.002), and muscle sympathetic nerve activity from 42±12 to 36±12 bursts/min ( P =0.004). Hypoxia increased systolic blood pressure 8±12 mm Hg ( P =0.057), heart rate 10±6 bpm ( P <0.001), muscle sympathetic nerve activity 7±7 bursts/min ( P =0.031), and ventilation 10±7 L/min ( P =0.002). However, responses to electrical carotid sinus stimulation did not differ between hypoxic and hyperoxic conditions: systolic blood pressure: -15±7 versus -14±8 mm Hg ( P =0.938), heart rate: -2±3 versus -2±2 bpm ( P =0.701), and muscle sympathetic nerve activity: -6±4 versus -4±3 bursts/min ( P =0.531). We conclude that moderate peripheral chemoreflex activation does not attenuate acute responses to electrical baroreflex activation therapy in patients with resistant hypertension. These patients provided insight into human baroreflex-chemoreflex interactions that could not be gained otherwise.

Baroreflex activation therapy (BAT) is a device-based therapy for patients with treatment-resistant hypertension. In a randomized, controlled trial, the first-generation system significantly reduced blood pressure (BP) versus sham. Although an open-label validation study of the second-generation system demonstrated similar BP reductions, controlled data are not presently available. Therefore, this investigation compares results of first- and second-generation BAT systems. Two cohorts of first-generation BAT system patients were generated with propensity matching to compare against the validation group of 30 second-generation subjects. The first cohort was drawn from the first-generation randomized trial sham group and the second cohort from the active therapy group. Safety and efficacy were compared for the second-generation group relative to the first generation. At 6 months, second-generation BAT outperformed first-generation sham systolic BP reduction by 20 ± 28 mm Hg (mean ± standard deviation, P = .008), while BP reduction in first- and second-generation active groups was similar. At 12 months, efficacy was comparable between all three groups after the sham group had received 6 months of therapy; 47% of second-generation patients achieved goal systolic BP of 140 mm Hg or less after 12 months, comparable to 50% of patients at goal in the first-generation group (P > .999). Implant procedure time, system/procedural safety, and pulse generator longevity improved with the second-generation system. Propensity-matched cohort analysis of the first- and second-generation BAT systems suggests similar therapeutic benefit and superior BP reduction of the second-generation system relative to sham control. Implantation procedure duration and perioperative safety were improved with the second-generation device. These findings should be validated in a prospective randomized trial., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Both baroreflex activation therapy (BAT) and renal denervation modulate sympathetic activity. The aim of this study was to systematically investigate whether additive modulation of autonomic nervous system by BAT lowers blood pressure (BP) in patients who still suffer from uncontrolled resistant hypertension despite prior renal denervation., Methods: From 2012 to January 2015, patients treated with BAT for uncontrolled resistant hypertension, who prior received renal denervation were consecutively analyzed in four German centers for hypertension. Analyses of office BP, 24-h ambulatory BP, central hemodynamics, parameters of renal function were performed., Results: A total of 28 patients, who underwent renal denervation at least 5 months before and still suffer from uncontrolled BP, were subsequently treated with BAT. The office SBP decreased from 182 ± 28 to 163 ± 27 mmHg (P < 0.01) with a responder rate of 68% (office SBP reduction ≥10 mmHg) at month 6, whereas the number of prescribed antihypertensive drug classes remained unchanged (6.2 ± 1.5 vs. 6.0 ± 1.7, P = 0.30). Serum creatinine, estimated glomerular filtration rate and cystatin C remained stable (P = 1.00, P = 0.41 and P = 0.22, respectively), whereas albuminuria was significantly reduced by a median of -29% (P = 0.02). Central SBP (-15 ± 24 mmHg, P = 0.047) and end systolic pressure (-14 ± 20 mmHg, P = 0.03) were significantly reduced., Conclusion: The present data demonstrate that BAT may exert BP-lowering as well as antiproteinuric effects in patients with prior renal denervation. However, precise evaluation of BAT effects in patients with prior renal denervation will need randomized controlled trials using sham procedures.

Background: Baroreflex activation therapy (BAT) by electrical stimulation of baroreceptors at the carotid sinus is a promising therapeutic approach to reduce elevated blood pressure (BP). To assess the efficacy of long-term BAT, we investigated acute BP alterations after device deactivation and reactivation (on/off effects) in patients on chronic BAT, as well as chronic BP reductions., Method: Resistant hypertension patients (n = 17) were enrolled in an open-label, single-arm evaluation of unilateral BAT after exclusion of secondary hypertension. Initial eligibility criteria were SBP≥  140 mmHg, despite stable medical therapy with at least three antihypertensive drugs including at least one diuretic. For on/off testing, several office cuff BP measurements were performed: at rest with activated device, 4-6 min after deactivation, and 4-6 min after reactivation., Results: Before BAT, mean office cuff BP was 179 ± 25 over 98 ± 18 mmHg. At the time of on/off testing (15.1 ± 8.7 months after initial activation and before deactivation), BP was reduced to 147 ± 29 over 84 ± 20 mmHg. On deactivation, SBP increased to 158 ± 38 mmHg (P = 0.004) and DBP to 89 ± 23 mmHg (P = 0.04). After reactivation, SBP decreased to 144 ± 34 mmHg (P = 0.002 vs. deactivation) and DBP to 83 ± 23 mmHg (P = 0.009). There was no correlation between duration of chronic BAT and systolic or diastolic acute on/off response., Conclusion: Unilateral BAT reduces BP in patients with resistant hypertension in the long term. There is a significant on/off effect on BP, supporting the efficacy of BAT. The acute on/off response to BAT does not depend on treatment duration. Thus, no evidence of tolerance over time to chronic BAT was found.

Aims: The Neo™ System (CVRx) is an implantable device, CE certified for the treatment of resistant hypertension and investigationally used to treat systolic heart failure by electrical stimulation of the carotid baroreceptors. It is unknown whether interaction might exist between the Neo System and implantable cardioverter-defibrillators (ICDs)., Methods and Results: Compatibility of the Neo device was tested in seven consecutive patients with pre-existing ICDs. Intra- and post-operative testing was completed with ICD and Neo settings programmed to provoke interaction. Intracardiac electrograms were printed to determine interaction with the ICD. Interaction testing during implantation and follow-up showed that there was no device-device interaction. No interaction was observed at maximum atrial and ventricular sensitivity settings and maximum Neo output settings., Conclusion: Combined therapy with the Neo device and at least in this study reported that transvenous ICD systems can be performed safely., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

We present a case of a patient with a baroreflex activation therapy (BAT) receiving a subcutaneous implantable cardioverter defibrillator (S-ICD). We anticipated two possible hazardous interactions between the two devices. Stimulation by the BAT could be adjudicated as noise and result in underdetection of ventricular arrhythmias or it might be misinterpreted as ventricular arrhythmias and lead to inappropriate shocks. Postop ensing occurred, the upper limit of pulse width of the BAT was limited because of noise detection by the S-ICD, but the upper limit of amplitude was limited by patient's discomfort. In this patient, the combination of a BAT and an S-ICD was safe. [ABSTRACT FROM AUTHOR]