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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.

Resume Depuis le debut des annees 2010, les technologies numeriques ont trouve une large application en cardiologie. La medecine connectee, ou sante digitale, qui en resulte utilise les technologies de l’information et de la communication pour colliger partager et analyser les informations a visee medicale. La fibrillation atriale qui est l’arythmie la plus frequente est une des plus grandes pourvoyeuses de complications emboliques et a type d’insuffisance cardiaque. Dans presque la moitie des cas, elle est cependant asymptomatique et ces technologies ont grandement aide a son diagnostic. Cet article passe en revue l’historique recent des technologies utilisees, et montre qu’elles sont a fort pouvoir diagnostique et influencent de la prise en charge therapeutique. L’introduction recente de l’intelligence artificielle augmente fortement la puissance diagnostique des technologies classiques et influencera dans un avenir proche considerablement les processus de decision.

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.

Background: Discrete choice experiment is a survey method used to understand how individuals make decisions and to quantify the relative importance of features. Using discrete choice experiment methods, we quantified patient benefit–risk preferences for hypertension treatments, including pharmaceutical and interventional treatments, like renal denervation. Methods: Respondents from the United States with physician-confirmed uncontrolled hypertension selected between treatments involving a procedure or pills, using a structured survey. Treatment features included interventional, noninterventional, or no hypertension treatment; number of daily blood pressure (BP) pills; expected reduction in office systolic BP; duration of effect; and risks of drug side effects, access site pain, or vascular injury. The results of a random–parameters logit model were used to estimate the importance of each treatment attribute. Results: Among 400 patients completing the survey between 2020 and 2021, demographics included: 52% women, mean age 59.2±13.0 years, systolic BP 155.1±12.3 mm Hg, and 1.8±0.9 prescribed antihypertensive medications. Reduction in office systolic BP was the most important treatment attribute. The remaining attributes, in decreasing order, were duration of effect, whether treatment was interventional, number of daily pills, risk of vascular injury, and risk of drug side effects. Risk of access site pain did not influence choice. In general, respondents preferred noninterventional over interventional treatments, yet only a 2.3 mm Hg reduction in office systolic BP was required to offset this preference. Small reductions in office systolic BP would offset risks of vascular injury or drug side effects. At least a 20% risk of vascular injury or drug side effects would be tolerated in exchange for improved BP. Conclusions: Reduction in systolic BP was identified as the most important driver of patient treatment preference, while treatment-related risks had less influence. The results indicate that respondents would accept interventional treatments in exchange for modest reductions in systolic BP compared with those observed in renal denervation trials.

Hypertension remains the leading cause of global mortality, with elevated systolic blood pressure (BP) leading to 10.8 million deaths each year. Despite this, only around 50% of individuals with hypertension are aware of their condition. Alongside low awareness rates, lack of patient adherence to medication and therapeutic inertia have been identified as factors contributing to the lack of hypertension control worldwide. This report summarizes presentations from the “one of a kind” Servier-sponsored symposium, Improving the Management of Hypertension: Acting on Key Factors, which was conducted as part of the European Society of Hypertension (ESH)-International Society of Hypertension (ISH) 2021 ON-AIR meeting. The symposium focused on how low awareness, therapeutic inertia, and nonadherence can be addressed by combining the experience of a patient with the expertise of physicians. May Measurement Month, the ongoing global BP measurement program, is raising awareness of hypertension in over 90 countries, and the 2018 European Society of Cardiology/ESH guidelines and the 2020 ISH guidelines now include recommendations that specifically address low adherence and therapeutic inertia, including involving patients in a shared decision-making process and the use of single-pill combination therapy. Understanding the role of emotion in decision making and addressing the different psychological states and attitudes in the patient’s “cycle of change” are key to effective shared decision making and improving adherence. Supplementary Information The online version contains supplementary material available at 10.1007/s40256-021-00505-6., Plain Language Summary Raised blood pressure (hypertension) is involved in the death of around 10.8 million people throughout the world each year. However, only about half of the people with hypertension are aware of their condition. In addition, many patients who are prescribed blood pressure-lowering medications do not take their pills regularly (intentional or nonintentional low adherence). Many doctors are not as strict as they should be in ensuring blood pressure control of their hypertensive patients (therapeutic inertia). This report presents ideas and data from a “first of its kind” symposium sponsored by Servier as part of the European Society of Hypertension (ESH)-International Society of Hypertension (ISH) 2021 ON-AIR meeting involving both patient and physicians. The report summarizes the ways in which low awareness, therapeutic inertia, and lack of adherence can be addressed and includes insights into patients’ perspectives. An ongoing global blood pressure screening program called May Measurement Month was discussed, which has detected almost a million people with untreated or inadequately treated hypertension worldwide since 2017. Recent ESH and ISH guidelines for managing hypertension now include recommendations on how to address low adherence and therapeutic inertia. Crucially, doctors should involve their patients with hypertension in decisions about their own treatment, which will help improve adherence to medication and ultimately reduce hypertension-related serious adverse events (e.g. heart attacks, strokes and deaths). Supplementary Information The online version contains supplementary material available at 10.1007/s40256-021-00505-6.

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.

The blood pressure (BP) lowering response to renal denervation (RDN) remains variable with about one-third of patients not responding to ultrasound or radiofrequency RDN. Identification of predictors of the BP response to RDN is needed to optimize patient selection for this therapy. This is a post-hoc analysis of the RADIANCE-HTN SOLO study. BP response to RDN was measured by the change in daytime ambulatory systolic blood pressure (dASBP) at 2 months post procedure. Univariate regression was used initially to assess potential predictors of outcome followed by multivariate regression analysis. In the univariate analysis, predictors of response to RDN were higher baseline daytime ambulatory diastolic blood pressure (dADBP), the use of antihypertensive medications at screening, and presence of orthostatic hypertension (OHTN) whilst the presence of untreated accessory arteries was a negative predictor of response. Multivariate analysis determined that dADBP and use of antihypertensive medications were predictors of response to RDN with a trend for OHTN to predict response. Obese females also appeared to be better responders to RDN in an interaction model. RDN is more effective in patients with elevated baseline dADBP and those with OHTN, suggesting increased peripheral vascular resistance secondary to heightened sympathetic tone. These assessments are easy to perform in clinical setting and may help in phenotyping patients who will respond better to RDN.

The continuous progress in cardiovascular (CV) risk prevention strategies has led to an impressive reduction in mortality and recurrent ischemic events in patients with coronary artery disease (CAD). However, the control of several CV risk factors remains suboptimal in many CAD patients, with a high rate of recurrent events, underlying the need for more new prevention strategies. The GAPS-I (GLP1 analogues, Antithrombotic agents, PCSK9 inhibitors, SGLT2 inhibitors and Immunomodulators) strategy offers a promising potential in patients with a high-residual CV risk, who are frequently encountered in daily practice, by offering an individualised and structured approach to addressing their individual risk factors. The current review summarises the evidence to date on each of its components, with respect to clinical outcomes and economic feasibility. The current evidence points to an efficacy of GAPS-I in reducing MACE and mortality, without a compromise on safety, albeit with the need for longer follow-up data. Key Points: - Secondary prevention remains suboptimal in many CAD patients, highlighting the need for innovative prevention strategies. - The present review discusses the current evidence on efficacy of the GAPS-I strategy in reducing MACE and mortality in patients with CAD. - The GAPS-I strategy, if widely adopted, provides a promising potential to assist cardiologists in managing patients at a heightened risk for further CV events.

Introduction – The current scientific literature suggests similar or even better catheter contact on caval regions of the cavo-tricuspid isthmus (CTI) compared to the more medial or annular part. Yet CTI ablation can be challenging owing to instability at the inferior vena cava (IVC) edge. No study specifically addressed the issue of catheter-tissue contact on caval/mid/annular regions of the CTI. Methods – Twenty-seven patients (22 men, 67±12 years) underwent typical atrial flutter ablation with a contact force (CF) sensing catheter (Tacticath 75, Abott) and were prospectively included. Operators aimed at optimizing CF for all RF pulses. The product of CF, time (force-time integral; FTI) and delivered power (FTPI) has been proposed as an estimate of lesion size. In a subset of 8 consecutive pts, electrograms (EGM) of all RF lesions were analyzed. Annular CTI was defined as sites showing both atrial and ventricular near-field bipolar EGM. Mid CTI sites had only atrial near field bipolar EGM on both distal and proximal dipoles (or distal only in case of superior-to-inferior approach). Caval sites had near-field bipolar EGM only in distal dipole, while the proximal one was inferiorly located. Results – Complete persistent (at 30 min) CTI block was obtained in all patients. A steerable sheath was used in 12 pts (44%). Procedure duration was 93±30 min, RF delivery time 10±6 min, fluoroscopy time 14±8 min. Mean CF was 15.8±5.9 g. CF was significantly lower (11.1±9.7 g) at the caval CTI than at mid CTI (19.9±11.8 g) and annular CTI (20±12.2 g; p=0.001). CF and FTI were higher during sinus rhythm than during Fl (23.2±15.3 vs 18.5±15.4 g, p=0.04 and 677±432 vs 532±357 gs, p=0.03). Use of a sheath improved mean CF (24.4±12.5 vs 18.4±14.9 g, p=0.01) but this was not significant at caval sites (17.5±11.4 vs 12.6±10.7 g, p=0.31). Conclusion – Applied forces are significantly lower at the IVC edge during CTI ablation. This supports the use of a steerable sheath in challenging cases.

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.

Aims The present study aimed to evaluate the potential of social media as an approach to recruit hypertensive subjects. Methods and results In addition to conventional trial recruitment, Facebook ads were run. Over a 115-day recruitment period, Facebook reached 5.3 million people in 168 separate campaigns run in the proximity of 19 sites in the USA and 14 sites in Europe. A total of 182 839 participants (3.4%) clicked on the ad; of those 10 483 subjects (5.7%) completed a dedicated questionnaire. This resulted in 3632 potential candidates. A total of 285 potential candidates were recruited by various recruitment strategies in the specified time period, of which 184/285 (64.6%) came from Facebook. When comparing Facebook with a 7-day radio spot in the same time period, 48 radio spots were launched; resulting in nine inquiries with eventually five potential candidates and two consents. Conclusion Targeted social media was a successful and efficient strategy to recruit hypertensive subjects.

Objective: To study patient and physician attitudes to pharmaceutical therapy and renal denervation for the management of hypertension. Methods: Data were analyzed from 19 market research studies in Western Europe and the United States conducted between 2010 and 2019 to obtain quantitative and qualitative perspectives. The analysis incorporated insights from 2768 patients and the experiences of 1902 physicians either actively performing or interested to perform device procedures, or hypertension specialists who would refer patients for a device-based intervention. Results: Referring cardiologists and proceduralists were more likely to recommend the renal denervation procedure to patients with higher BP levels and a greater number of antihypertensive medications. Physicians perceived patient reluctance towards a procedure as an important obstacle to recommending renal denervation as a treatment option for uncontrolled hypertension. Patient interest in the renal denervation procedure did not correlate with BP severity (P = NS), and the highest preference for the procedure was in patients diagnosed with hypertension but not receiving treatment (P

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. 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. We observed a significant decrease of QTpeak (p p 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.

The present investigation was started with aim to formulate and assess the antimicrobial potential of Punica granatum seed oil cream. The P. granatum seed oil cream was formulated using glyceryl monostearate and other lipids like stearic acid as well as cetyl alcohol. The formulated cream was then evaluated with respect to physicochemical properties and in vitro antimicrobial activity against Escherichia coli. The formulated oil loaded cream showed acceptable physicochemical properties like pH, spreadability, type of emulsion and viscosity which confer its suitability for topical application. In addition to this, the in vitro antimicrobial potential of oil loaded cream against E. coli was also found to be acceptable. Thus, formulated cream could be promising alternative for topical application of P. granatum seed oil with better antimicrobial potential.

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 beta(1)-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.

Suboptimal adherence to antihypertensive medication is a major contributor to poor blood pressure control. Several methods, direct or indirect, are available for measuring adherence, including the recently developed biochemical screening, although there is no gold-standard method routinely used in clinical practice to accurately assess the different facets of adherence. Adherence to treatment is a complex phenomenon and several of the barriers to adherence will need to be addressed at the healthcare system level; however, when looking at adherence from a more practical side and from the practitioner's perspective, the patient-practitioner relationship is a key element both in detecting adherence and in attempting to choose interventions tailored to the patient's profile. The use of single-pill combinations enabling simplification of treatment regimen, the implementation of a collaborative team-based approach and the development of electronic health tools also hold promise for improving adherence, and thus impacting cardiovascular outcomes and healthcare costs.

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.

Summary 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.

La place des anticorps thérapeutiques dans les maladies cardiovasculaires et métaboliques est encore modeste en 2019 en comparaison à leur incroyable développement dans d’autres champs pathologiques. Cependant, l’arrivée récente des anticorps anti-PCSK9 (proprotein convertase subtilisin/kexin de type 9) dans l’arsenal thérapeutique va probablement changer la donne. Ces anticorps permettent non seulement d’améliorer la prise en charge des patients porteurs d’hypercholestérolémie familiale mais également de réduire le risque de complications cliniques de l’athérosclérose en prévention secondaire après un infarctus du myocarde, une artériopathie périphérique ou un accident vasculaire cérébral ischémique. D’autres stratégies thérapeutiques sont en cours d’investigation, ciblant notamment des cellules et cytokines impliquées dans les réponses immuno-inflammatoires avec pour objectif de prévenir les complications de l’athérosclérose ou les lésions du myocarde au décours d’un infarctus.

Background: The multicenter, international, randomized, blinded, sham-controlled RADIANCE-HTN SOLO trial (A Study of the ReCor Medical Paradise System in Clinical Hypertension) demonstrated a 6.3 mm Hg greater reduction in daytime ambulatory systolic blood pressure (BP) at 2 months by endovascular ultrasound renal denervation (RDN) compared with a sham procedure among patients not treated with antihypertensive medications. We report 6-month results after the addition of a recommended standardized stepped-care antihypertensive treatment to the randomized endovascular procedure under continued blinding to initial treatment. Methods: Patients with a daytime ambulatory BP ≥135/85 mm Hg and Results: A total of 69/74 RDN patients and 71/72 sham patients completed the 6-month ambulatory BP measurement. At 6 months, 65.2% of patients in the RDN group were treated with the standardized stepped-care antihypertensive treatment versus 84.5% in the sham group ( P =0.008), and the average number of antihypertensive medications and defined daily dose were less in the RDN group than in the sham group (0.9±0.9 versus 1.3±0.9, P =0.010 and 1.4±1.5 versus 2.0±1.8, P =0.018; respectively). Despite less intensive standardized stepped-care antihypertensive treatment, RDN reduced daytime ambulatory systolic BP to a greater extent than sham (−18.1±12.2 versus −15.6±13.2 mm Hg, respectively; difference adjusted for baseline BP and number of medications: −4.3 mm Hg, 95% confidence interval, −7.9 to −0.6, P =0.024). There were no major adverse events in either group through 6 months. Conclusions: The BP-lowering effect of endovascular ultrasound RDN was maintained at 6 months with less prescribed antihypertensive medications compared with a sham control. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02649426.

The Dunning-Kruger premise assumes that unqualified people are unaware of their limited skills. We tested this hypothesis in the context of the coronavirus disease 2019 (COVID-19) pandemic. In this cross-sectional study, 2487 participants had to self-estimate their knowledge about COVID-19 in a questionnaire on the topic. Poor performers were more likely to use mass media and social networks as sources of information and had lower levels of education. The mean self-assessment (SD) was 6.88 (2.06) and was not linked to actual level of knowledge. This observation should prompt regulatory agencies and media to apply rules that limit dissemination of “infodemics” during global health crises.

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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.

Cationic polymers (i.e. polyallylamine, poly-L-lysine) having primary amino groups are poor transfection agents and possess high cytotoxicity index when used without any chemical modification and usually entail specific receptor mediated endocytosis or lysosomotropic agents to execute efficient gene delivery. In this report, primary amino groups of polyallylamine (PAA, 17 kDa) were substituted with imidazolyl functions, which are presumed to enhance endosomal release, and thus enhance its gene delivery efficiency and eliminate the requirement of external lysosomotropic agents. Further, systems were cross-linked with polyethylene glycol (PEG) to prepare PAA-IAA-PEG (PIP) nanoparticles and evaluated them in various model cell lines. The efficacy of PIP nanoparticles in delivering a plasmid encoding enhanced green fluorescent protein (EGFP) gene was assessed in COS-1, N2a and HEK293 cell lines, while their cytotoxicity was investigated in COS-1 and HEK293 cell lines. The PAA was chemically modified using imidazolyl moieties and ionically cross-linked with PEG to engineer nanoparticles. The extent of substitution was determined by ninhydrin method. The PIP nanoparticles were further characterized by measuring the particle size (dynamic light scattering and transmission electron microscopy), surface charge (zeta potential), DNA accessibility and buffering capacity. The cytotoxicity was examined using the MTT method. In vitro transfection efficiency of synthesized nanoparticles is increased up to several folds compared to native polymer even in the presence of serum, while maintaining the cell viability over 100% in COS-1 cells. Nanoparticles possess positive zeta potential between 5.6–13 mV and size range of 185–230 nm in water. The accessibility experiment demonstrated that nanoparticles with higher degree of imidazolyl substitution formed relatively loose complexes with DNA. An acid-base titration showed enhanced buffering capacity of modified PAA. The PIP nanoparticles reveal tremendous potential as novel delivery system for achieving improved transfection efficiency, while keeping the cells at ease.