Effect of Alcohol-Mediated Renal Denervation on Blood Pressure in the Presence of Antihypertensive Medications: Primary Results From the TARGET BP I Randomized Clinical Trial.

BACKGROUND: Renal denervation (RDN) has demonstrated clinically relevant reductions in blood pressure (BP) among individuals with uncontrolled hypertension despite lifestyle intervention and medications. The safety and effectiveness of alcohol-mediated RDN have not been formally studied in this indication. METHODS: TARGET BP I is a prospective, international, sham-controlled, randomized, patient- and assessor-blinded trial investigating the safety and efficacy of alcohol-mediated RDN. Patients with office systolic BP (SBP) ≥150 and ≤180 mm Hg, office diastolic BP ≥90 mm Hg, and mean 24-hour ambulatory SBP ≥135 and ≤170 mm Hg despite prescription of 2 to 5 antihypertensive medications were enrolled. The primary end point was the baseline-adjusted change in mean 24-hour ambulatory SBP 3 months after the procedure. Secondary end points included mean between-group differences in office and ambulatory BP at additional time points. RESULTS: Among 301 patients randomized 1:1 to RDN or sham control, RDN was associated with a significant reduction in 24-hour ambulatory SBP at 3 months (mean±SD, -10.0±14.2 mm Hg versus -6.8±12.1 mm Hg; treatment difference, -3.2 mm Hg [95% CI, -6.3 to 0.0]; P=0.0487). Subgroup analysis of the primary end point revealed no significant interaction across predefined subgroups. At 3 months, the mean change in office SBP was -12.7±18.3 and -9.7±17.3 mm Hg (difference, -3.0 [95% CI, -7.0 to 1.0]; P=0.173) for RDN and sham, respectively. No significant differences in ambulatory or office diastolic BP were observed. Adverse safety events through 6 months were uncommon, with one instance of accessory renal artery dissection in the RDN group (0.7%). No significant between-group differences in medication changes or patient adherence were identified. CONCLUSIONS: Alcohol-mediated RDN was associated with a modest but statistically significant reduction in 24-hour ambulatory SBP compared with sham control. No significant differences between groups in office BP or 6-month major adverse events were observed. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02910414.

Renal denervation in the management of hypertension in adults. A clinical consensus statement of the ESC Council on Hypertension and the European Association of Percutaneous Cardiovascular Interventions (EAPCI).

Since the publication of the 2018 European Society of Cardiology/European Society of Hypertension (ESC/ESH) Guidelines for the Management of Arterial Hypertension, several high-quality studies, including randomised, sham-controlled trials on catheter-based renal denervation (RDN) were published, confirming both the blood pressure (BP)-lowering efficacy and safety of radiofrequency and ultrasound RDN in a broad range of patients with hypertension, including resistant hypertension. A clinical consensus document by the ESC Council on Hypertension and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) on RDN in the management of hypertension was considered necessary to inform clinical practice. This expert group proposes that RDN is an adjunct treatment option in uncontrolled resistant hypertension, confirmed by ambulatory BP measurements, despite best efforts at lifestyle and pharmacological interventions. RDN may also be used in patients who are unable to tolerate antihypertensive medications in the long term. A shared decision-making process is a key feature and preferably includes a patient who is well informed on the benefits and limitations of the procedure. The decision-making process should take (i) the patient's global cardiovascular (CV) risk and/or (ii) the presence of hypertension-mediated organ damage or CV complications into account. Multidisciplinary hypertension teams involving hypertension experts and interventionalists evaluate the indication and facilitate the RDN procedure. Interventionalists require expertise in renal interventions and specific training in RDN procedures. Centres performing these procedures require the skills and resources to deal with potential complications. Future research is needed to address open questions and investigate the impact of BP-lowering with RDN on clinical outcomes and potential clinical indications beyond hypertension.

Clinical Trial Design Principles and Outcomes Definitions for Device-Based Therapies for Hypertension: A Consensus Document From the Hypertension Academic Research Consortium.

The clinical implications of hypertension in addition to a high prevalence of both uncontrolled blood pressure and medication nonadherence promote interest in developing device-based approaches to hypertension treatment. The expansion of device-based therapies and ongoing clinical trials underscores the need for consistency in trial design, conduct, and definitions of clinical study elements to permit trial comparability and data poolability. Standardizing methods of blood pressure assessment, effectiveness measures beyond blood pressure alone, and safety outcomes are paramount. The Hypertension Academic Research Consortium (HARC) document represents an integration of evolving evidence and consensus opinion among leading experts in cardiovascular medicine and hypertension research with regulatory perspectives on clinical trial design and methodology. The HARC document integrates the collective information among device-based therapies for hypertension to better address existing challenges and identify unmet needs for technologies proposed to treat the world's leading cause of death and disability. Consistent with the Academic Research Consortium charter, this document proposes pragmatic consensus clinical design principles and outcomes definitions for studies aimed at evaluating device-based hypertension therapies.

Analysis of Motor Vehicle Accidents: Comparison Between Before and During the COVID-19 Lockdown in Maharashtra, India.

To prevent the pandemic spread of human-to-human transmitted diseases such as COVID-19, governments commonly resort to countrywide or regional lockdown strategies. Such lockdowns, whenever and wherever implemented, curtail the movement of persons and vehicles, and drastically alter traffic conditions. This study focuses on the effect of drastic and sudden changes in the traffic conditions, during the COVID-19 lockdown in the State of Maharashtra in India, in March-June 2020, on the numbers of motor vehicle accidents (MVAs), and the resultant fatalities and injuries. Content analysis of police-reported first information reports (FIRs) of MVAs is performed, and these lockdown trends are compared with archival data from corresponding previous (normal) periods. The statistical analysis shows that, during the lockdown, while the total number of MVAs fall drastically, they are more severe and have a much higher fatality rate per MVA. Also, the pattern of vehicles involved in MVAs, and resultant pattern of fatalities, also changes during lockdowns. The paper explores the reasons for these changed patterns and provides suggestions to reduce these negative externalities of pandemic related lockdowns.

Ultrasound renal denervation for hypertension resistant to a triple medication pill (RADIANCE-HTN TRIO): a randomised, multicentre, single-blind, sham-controlled trial.

BACKGROUND: Endovascular renal denervation reduces blood pressure in patients with mild-to-moderate hypertension, but its efficacy in patients with true resistant hypertension has not been shown. We aimed to assess the efficacy and safety of endovascular ultrasound renal denervation in patients with hypertension resistant to three or more antihypertensive medications. METHODS: In a randomised, international, multicentre, single-blind, sham-controlled trial done at 28 tertiary centres in the USA and 25 in Europe, we included patients aged 18-75 years with office blood pressure of at least 140/90 mm Hg despite three or more antihypertensive medications including a diuretic. Eligible patients were switched to a once daily, fixed-dose, single-pill combination of a calcium channel blocker, an angiotensin receptor blocker, and a thiazide diuretic. After 4 weeks of standardised therapy, patients with daytime ambulatory blood pressure of at least 135/85 mm Hg were randomly assigned (1:1) by computer (stratified by centres) to ultrasound renal denervation or a sham procedure. Patients and outcome assessors were masked to randomisation. Addition of antihypertensive medications was allowed if specified blood pressure thresholds were exceeded. The primary endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Safety was also assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02649426. FINDINGS: Between March 11, 2016, and March 13, 2020, 989 participants were enrolled and 136 were randomly assigned to renal denervation (n=69) or a sham procedure (n=67). Full adherence to the combination medications at 2 months among patients with urine samples was similar in both groups (42 [82%] of 51 in the renal denervation group vs 47 [82%] of 57 in the sham procedure group; p=0·99). Renal denervation reduced daytime ambulatory systolic blood pressure more than the sham procedure (-8·0 mm Hg [IQR -16·4 to 0·0] vs -3·0 mm Hg [-10·3 to 1·8]; median between-group difference -4·5 mm Hg [95% CI -8·5 to -0·3]; adjusted p=0·022); the median between-group difference was -5·8 mm Hg (95% CI -9·7 to -1·6; adjusted p=0·0051) among patients with complete ambulatory blood pressure data. There were no differences in safety outcomes between the two groups. INTERPRETATION: Compared with a sham procedure, ultrasound renal denervation reduced blood pressure at 2 months in patients with hypertension resistant to a standardised triple combination pill. If the blood pressure lowering effect and safety of renal denervation are maintained in the long term, renal denervation might be an alternative to the addition of further antihypertensive medications in patients with resistant hypertension. FUNDING: ReCor Medical.

Diverse pharmacological properties, trial results, comorbidity prescribing and neural pathophysiology suggest European hypertension guideline downgrading of beta-blockers is not justified.

Beta-blockers have solid documentation in preventing cardiovascular complications in the treatment of hypertension; atenolol, metoprolol, oxprenolol and propranolol demonstrate proven cardiovascular prevention in hypertension mega-trials. Hypertension is characterised by activation of the sympathetic nervous system from early to late phases, which makes beta-blockers an appropriate treatment seen from a pathophysiological viewpoint, especially in patients with an elevated heart rate. Beta-blockers represent a heterogenous class of drugs with regard to both pharmacodynamic and pharmacokinetic properties. This position is manifest by reference to another clinical context, beta-blocker treatment of heart failure, where unequivocally there is no class effect (no similar benefit from all beta-blockers); there are good and less good beta-blockers for heart failure. Analogous differences in beta-blocker efficacy is also likely in hypertension. Beta-blockers are widely used for the treatment of diseases comorbid with hypertension, in approximately 50 different concomitant medical conditions that are frequent in patients with hypertension, leading to many de facto beta-blocker first choices in clinical practice. Thus, beta-blockers should be regarded as relevant first choices for hypertension in clinical practice, particularly if characterised by a long half-life, highly selective beta-1 blocking activity and no intrinsic agonist properties.SUMMARYBeta-blockers have solid documentation in preventing cardiovascular complications in the treatment of hypertension; atenolol, metoprolol, oxprenolol and propranolol demonstrate proven cardiovascular prevention in hypertension mega-trialsHypertension is characterised by activation of the sympathetic nervous system from early to late phases, which makes beta-blockers an appropriate treatment seen from a pathophysiological viewpoint, especially in patients with an elevated heart rateBeta-blockers represent a heterogenous class of drugs with regard to both pharmacodynamic and pharmacokinetic propertiesThis position is manifest by reference to another clinical context, beta-blocker treatment of heart failure, where unequivocally there is no class effect (no similar benefit from all beta-blockers); there are good and less good beta-blockers for heart failureAnalogous differences in beta-blocker efficacy is also likely in hypertensionBeta-blockers are widely used for the treatment of diseases comorbid with hypertension, in approximately 50 different concomitant medical conditions that are frequent in patients with hypertension, leading to many de facto beta-blockers first choices in clinical practiceThese observations, in totality, inform our opinion that beta-blockers are relevant first choices for hypertension in clinical practice and this fact needs highlightingFurther, these arguments suggest European hypertension guideline downgrading of beta-blockers is not justified.

Catheter-based alcohol-mediated renal denervation for the treatment of uncontrolled hypertension: design of two sham-controlled, randomized, blinded trials in the absence (TARGET BP OFF-MED) and presence (TARGET BP I) of antihypertensive medications.

BACKGROUND: Arterial hypertension is a common and life-threatening condition and poses a large global health burden. Device-based treatments have been developed as adjunctive or alternative therapy, to be used with or without antihypertensive medication for treating uncontrolled hypertension. The safety and feasibility of chemical renal denervation (RDN) using the Peregrine Catheter and alcohol were demonstrated in a first-in-man and open-label clinical trials, prompting the initiation of the ongoing TARGET BP OFF-MED and TARGET BP I trials. DESIGN: The TARGET BP trials are randomized, blinded, sham-controlled trials designed to assess the safety and efficacy of alcohol-mediated RDN for the treatment of uncontrolled hypertension in the absence of antihypertensive medications (TARGET BP OFF-MED) or in addition to prescribed antihypertensive medications (TARGET BP I). Subjects with confirmed uncontrolled hypertension and suitable renal artery anatomy are randomized (1:1) to receive either RDN using the Peregrine Kit with alcohol (0.6 mL per renal artery) infused through the Peregrine Catheter or diagnostic renal angiography only (sham procedure). TARGET BP OFF-MED completed enrollment and randomized 96 subjects. TARGET BP I will randomize approximately 300 subjects and will transition to an open-label safety cohort of approximately 300 subjects receiving RDN once the primary efficacy endpoint of the Randomized Controlled Trial (RCT) cohort has been met. Primary endpoints are change in mean 24-hour ambulatory systolic blood pressure from baseline to 8 weeks (TARGET BP OFF-MED) and 3 months (TARGET BP I) post-procedure. CONCLUSION: The TARGET BP trials are the first large-scale, international, randomized trials aimed to investigate the safety and BP lowering efficacy of a novel RDN method, with perivascular alcohol delivery using the Peregrine Kit.

Sequential ultrahigh-density contact mapping of persistent atrial fibrillation: An efficient technique for driver identification.

INTRODUCTION: Literature supports the existence of drivers as maintainers of atrial fibrillation (AF). Whether ultrahigh density (UHD) contact mapping may detect them is unknown. METHODS: We sequentially mapped the left atrial (LA) activation during spontaneous persistent AF and performed circumferential pulmonary vein isolation (CPVI), followed by remapping and ablation of potential drivers (rotational and focal propagation sites) with Rhythmia™ in 90 patients. The time reference was an LA appendage (LAA) electrogram (EGM). Regions with uniform color were defined as "organized." Only patients (51) with no previous ablation were considered for acute results and follow-up reporting. RESULTS: LA maps (175 ± 28 ml, 43578 ± 18013 EGM) were acquired in 23 ± 7 min. In all post-CPVI maps potential drivers (7.3 ± 3.2/patient) were visualized: 85% with rotational propagation and continuous low voltage in the center; the remaining with focal propagation and an organized EGM at the site of earliest activation. The RF delivery time for extra-PV driver ablation was 12.2 ± 7.9 min. There was a progressive increase of AF organization: the LAA cycle length prolonged, the number of potential drivers decreased, and the organized LA surface in AF increased from 14 ± 6% to 28 ± 16% (p = .0007). Termination of AF without cardioversion was obtained in 67%. AF recurrence rate at 15 ± 7.3 months was 17.6% after the first procedure. CONCLUSIONS: Sequential UHD contact activation mapping of persistent AF allows visualization of potential drivers. A sequential strategy of CPVI followed by ablation of potential drivers with limited RF time resulted in an increasing organization of AF and good acute and long-term results.

Blood pressure lowering with alcohol-mediated renal denervation using the Peregrine infusion Catheter is independent of injection site location.

OBJECTIVES: The current analysis utilized core laboratory angiographic data from a prospective, single-arm, open-label, multi-center feasibility study to ascertain whether the location of alcohol infusion within main renal arteries during renal denervation (RDN) had an impact on the BP-lowering effect at 6 months. BACKGROUND: The influence of the location of alcohol infusion during RDN, within the main renal artery (proximal, middle, or distal), on the magnitude of the blood pressure (BP) lowering is unstudied. METHODS: The Peregrine Catheter was used to perform alcohol-mediated RDN with an infusion of 0.6 mL of alcohol per artery as the neurolytic agent in 90 main arteries and four accessory arteries of 45 patients with hypertension. RESULTS: No relationship between the site of alcohol infusion and change from baseline in both office systolic and 24-hour systolic ambulatory BP (ABP) at 6 months was observed. When analyzed at the artery level, the least squares (LS) mean changes ± SEM from baseline to 6 months post-procedure in 24-hour systolic ABP when analyzed by renal arterial location were -11.9 ± 2.4 mmHg (distal), -10 ± 1.6 mmHg (middle), and -10.6 ± 1.3 mmHg (proximal) (all p < 0.0001 for change from baseline within groups). The results were similar for office systolic BP. There was no difference between treated locations (proximal is reference). CONCLUSION: In this post-hoc analysis, the location of alcohol infusion within the main renal artery using the Peregrine system, with alcohol as the neurolytic agent for chemical RDN, did not affect the magnitude of BP changes at 6 months.

Managing plastic packaging waste in emerging economies: The case of EPR in India.

India's large population, rapidly growing economy, and the consequent rising plastic waste, has necessitated the need for an efficient and effective plastic waste management (PWM) system for ensuring an environmentally cleaner and sustainable future. Consequently, PWM policy in India has recently undergone a substantial shift from being an informally organized, largely uncoordinated set of programs towards becoming a formal and integrated system based on the extended producer responsibility (EPR) approach. This paper explicates the evolution, development, implementation, and implications of the Indian EPR framework for PWM by developing an integrative mixed-method case study. Using a theory-based stakeholder evaluation model, the study critically analyzes the drivers and constraining factors from a multi-stakeholder perspective and provides prescriptive suggestions on EPR policy formulation and implementation. It highlights three themes i.e., (a) robust regulatory architecture; (b) operational mechanism; and (c) ecosystem catalysts, whose nature, dynamics, and practicality shall determine the future of the Indian EPR framework and those of comparable emerging economies.

Cardiovascular Magnetic Resonance May Avoid Unnecessary Coronary Angiography in Patients With Unexplained Left Ventricular Systolic Dysfunction: A Retrospective Diagnostic Pilot Study.

BACKGROUND: Coronary angiography (CA) is usually performed in patients with reduced left ventricular ejection fraction (LVEF) to search ischemic cardiomyopathy. Our aim was to examine the agreement between CA and cardiovascular magnetic resonance (CMR) imaging among a cohort of patients with unexplained reduced LVEF, and estimate what would have been the consequences of using CMR imaging as the first-line examination. METHODS: Three hundred five patients with unexplained reduced LVEF of ≤45% who underwent both CA and CMR imaging were retrospectively registered. Patients were classified as CMR+ or CMR- according to presence or absence of myocardial ischemic scar, and classified CA+ or CA- according to presence or absence of significant coronary artery disease. RESULTS: CMR+ (n = 89) included all 54 CA+ patients, except 2 with distal coronary artery disease in whom no revascularization was proposed. Among the 247 CA- patients, 15% were CMR+. CMR imaging had 96% sensitivity, 85% specificity, 99% negative predictive value, and 58% positive predictive value for detecting CA+ patients. Revascularization was performed in 6.5% of the patients (all CMR+). Performing CA only for CMR+ patients would have decreased the number of CAs by 71%. CONCLUSIONS: In reduced LVEF, performing CA only in CMR+ patients may significantly decrease the number of unnecessary CAs performed, without missing any patients requiring revascularization.

Retraction Note: Engineered Polyallylamine Nanoparticles for Efficient In Vitro Transfection.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1007/s11095-020-02971-0.

Role of Metoprolol Succinate in the Treatment of Heart Failure and Atrial Fibrillation: A Systematic Review.

BACKGROUND: Beta-blockers are one of the most important classes of cardiovascular agents and have been considered a cornerstone therapy in heart diseases, such as heart failure (HF) and atrial fibrillation (AF). Among different beta-blockers, metoprolol is a selective beta1-adrenergic antagonist, which has been extensively used since the 1970s. AREAS OF UNCERTAINTY: Although current guidelines include recommendations for the use of controlled-release metoprolol succinate in specific HF and AF indications, and despite extensive clinical experience with metoprolol, comparative evidence on the use of metoprolol succinate compared with other beta-blockers in these indications is limited. DATA SOURCES: We systematically reviewed the data from head-to-head studies directly comparing this compound with other beta-blockers in the treatment of HF or AF. Only clinical trials and observational studies were considered; no other limits were applied. The quality and relevance of retrieved articles were reviewed. RESULTS: A total of 18 articles of the 353 articles identified were selected for inclusion; 12 HF articles and 6 for AF. Additional references were identified from the bibliographies of retrieved articles. The studies show that oral prophylaxis with an appropriate dose of metoprolol may reduce new incidents of AF in high-risk patients. Furthermore, metoprolol succinate is associated with significant mortality and morbidity benefits in the treatment of HF. CONCLUSIONS: Despite the introduction of newer beta-blockers with differing clinical characteristics since its introduction, metoprolol succinate remains a useful drug in both HF and AF.

Observations on changes in ventricular repolarization following four weeks of exercise training in chronic heart failure patients.

OBJECTIVE: The aim of this study was to investigate the effects of exercise training on ventricular repolarization dynamicity and heart rate variability in chronic heart failure patients. DESIGN: A total of 22 chronic heart failure patients with reduced ejection fraction in sinus rhythm were included in the study. The patients were in NYHA classes II-III with an ejection fraction of 29.7 ± 7.7%. Before and after 4 weeks of aerobic exercise training, all patients performed a cardiopulmonary exercise test, a standard twelve-lead electrocardiogram and a 24 h Holter recording from which heart rate variability and ventricular repolarization dynamicity were assessed. RESULTS: We observed a significant decrease of QTpeak (p < .001) and QTend (p < .001) at RR intervals ranging from 600 to 1000 ms on 24 h QT/RR regressions after 4 weeks of exercise training. Our analyses revealed that short-term exercise training induced significant changes in the frequency and time domain HRV parameters on an overall time-period of 24 h. CONCLUSION: Four weeks of exercise training induced significant changes in ventricular repolarization dynamicity in chronic heart failure patients. In addition, short-term exercise training was enough to improve patients' heart rate variability.

Interventional procedures and future drug therapy for hypertension.

Hypertension management poses a major challenge to clinicians globally once non-drug (lifestyle) measures have failed to control blood pressure (BP). Although drug treatment strategies to lower BP are well described, poor control rates of hypertension, even in the first world, suggest that more needs to be done to surmount the problem. A major issue is non-adherence to antihypertensive drugs, which is caused in part by drug intolerance due to side effects. More effective antihypertensive drugs are therefore required which have excellent tolerability and safety profiles in addition to being efficacious. For those patients who either do not tolerate or wish to take medication for hypertension or in whom BP control is not attained despite multiple antihypertensives, a novel class of interventional procedures to manage hypertension has emerged. While most of these target various aspects of the sympathetic nervous system regulation of BP, an additional procedure is now available, which addresses mechanical aspects of the circulation. Most of these new devices are supported by early and encouraging evidence for both safety and efficacy, although it is clear that more rigorous randomized controlled trial data will be essential before any of the technologies can be adopted as a standard of care.

Dual agonist occupancy of AT1-R-α2C-AR heterodimers results in atypical Gs-PKA signaling.

Hypersecretion of norepinephrine (NE) and angiotensin II (AngII) is a hallmark of major prevalent cardiovascular diseases that contribute to cardiac pathophysiology and morbidity. Herein, we explore whether heterodimerization of presynaptic AngII AT1 receptor (AT1-R) and NE α2C-adrenergic receptor (α2C-AR) could underlie their functional cross-talk to control NE secretion. Multiple bioluminescence resonance energy transfer and protein complementation assays allowed us to accurately probe the structures and functions of the α2C-AR-AT1-R dimer promoted by ligand binding to individual protomers. We found that dual agonist occupancy resulted in a conformation of the heterodimer different from that induced by active individual protomers and triggered atypical Gs-cAMP-PKA signaling. This specific pharmacological signaling unit was identified in vivo to promote not only NE hypersecretion in sympathetic neurons but also sympathetic hyperactivity in mice. Thus, we uncovered a new process by which GPCR heterodimerization creates an original functional pharmacological entity and that could constitute a promising new target in cardiovascular therapeutics.

Sympathetic nervous response to ischemia-reperfusion injury in humans is altered with remote ischemic preconditioning.

Sympathetic neural activation may be detrimentally involved in tissue injury caused by ischemia-reperfusion (IR). We examined the effects of experimental IR in the forearm on sympathetic nerve response, finger reactive hyperemia, and oxidative stress, and the protection afforded by applying remote ischemic preconditioning (RIPC). Ischemia was induced in the forearm for 20 min in healthy volunteers. RIPC was induced by applying two cycles, 5 min each, of ischemia and reperfusion to the upper leg immediately before IR. We examined muscle sympathetic nerve activity (MSNA) in the contralateral leg using microneurography, finger reactive hyperemia [ischemic reactive hyperemia index (RHI)], erythrocyte production of reduced gluthathione (GSH), and plasma nitric oxide (NO) concentration. In controls (no RIPC; n = 15), IR increased MSNA in the early and late phase of ischemia (70% at 5 min; 101% at 15 min). In subjects who underwent RIPC (n = 15), the increase in MSNA was delayed to the late phase of ischemia and increased only by 40%. GSH increased during ischemia in the control group (P = 0.05), but not in those who underwent RIPC. Nitrate and nitrite concentration, taken as an index of NO availability, decreased during the reperfusion period in control individuals (P < 0.05), while no change was observed in those who underwent RIPC. Experimental IR did not affect RHI in the control condition, but a significant vasodilatory response occurred in the RIPC group (P < 0.05). RIPC attenuated ischemia-induced sympathetic activation, prevented the production of an erythrocyte marker of oxidative stress and the reduction of NO availability, and ameliorated RHI.

Device-based Therapy for Hypertension.

Hypertension continues to be a major contributor to global morbidity and mortality, fuelled by an abundance of patients with uncontrolled blood pressure despite the multitude of pharmacological options available. This may occur as a consequence of true resistant hypertension, through an inability to tolerate current pharmacological therapies, or non-adherence to antihypertensive medication. In recent years, there has been a rapid expansion of device-based therapies proposed as novel non-pharmacological approaches to treating resistant hypertension. In this review, we discuss seven novel devices-renal nerve denervation, baroreflex activation therapy, carotid body ablation, central iliac arteriovenous anastomosis, deep brain stimulation, median nerve stimulation, and vagal nerve stimulation. We highlight how the devices differ, the varying degrees of evidence available to date and upcoming trials. This review also considers the possible factors that may enable appropriate device selection for different hypertension phenotypes.