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BACKGROUND: Cardiac resynchronization therapy (CRT) decreases mortality, improves functional status, and induces reverse left ventricular remodeling in selected populations with heart failure. We aimed to assess the impact of baseline QRS duration and morphology and the change in QRS duration with pacing on CRT outcomes in mild heart failure. METHODS AND RESULTS: Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) was a multicenter randomized trial of CRT among 610 patients with mild heart failure. Baseline and CRT-paced QRS durations and baseline QRS morphology were evaluated by blinded core laboratories. The mean baseline QRS duration was 151±23 milliseconds, and 60.5% of subjects had left bundle-branch block (LBBB). Patients with LBBB experienced a 25.3-mL/m(2) mean reduction in left ventricular end-systolic volume index (P<0.0001), whereas non-LBBB patients had smaller decreases (6.7 mL/m(2); P=0.18). Baseline QRS duration was also a strong predictor of change in left ventricular end-systolic volume index with monotonic increases as QRS duration prolonged. Similarly, the clinical composite score improved with CRT for LBBB subjects (odds ratio, 0.530; P=0.0034) but not for non-LBBB subjects (odds ratio, 0.724; P=0.21). The association between clinical composite score and QRS duration was highly significant (odds ratio, 0.831 for each 10-millisecond increase in QRS duration; P<0.0001), with improved response at longer QRS durations. The change in QRS duration with CRT pacing was not an independent predictor of any outcomes after correction for baseline variables. CONCLUSION: REVERSE demonstrated that LBBB and QRS prolongation are markers of reverse remodeling and clinical benefit with CRT in mild heart failure. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00271154. [ABSTRACT FROM AUTHOR]

Background: Airway clearance (ACT) and lung volume recruitment (LVR) techniques are used to manage bronchial secretions, increase cough efficiency and lung/chest wall recruitment, to prevent and treat respiratory tract infections. The aim of the study was to review the prescription of ACT/LVR techniques for home use in children in France., Methods: All the centers of the national pediatric noninvasive ventilation (NIV) network were invited to fill in an anonymous questionnaire for every child aged ≤20 years who started a treatment with an ACT/LVR device between 2022 and 2023. The devices comprised mechanical in-exsufflation (MI-E), intermittent positive pressure breathing (IPPB), intrapulmonary percussive ventilation (IPV), and/or invasive mechanical ventilation (IMV)/NIV for ACT/LVR., Results: One hundred and thirty-nine patients were included by 13 centers. IPPB was started in 83 (60 %) patients, MI-E in 43 (31 %) and IPV in 30 (22 %). No patient used IMV/NIV for ACT/LVR. The devices were prescribed mainly by pediatric pulmonologists (103, 74 %). Mean age at initiation was 8.9 ± 5.6 (0.4-18.5) years old. The ACT/LVR devices were prescribed mainly in patients with neuromuscular disorders (n = 66, 47 %) and neurodisability (n = 37, 27 %). The main initiation criteria were cough assistance (81 %) and airway clearance (60 %) for MI-E, thoracic mobilization (63 %) and vital capacity (47 %) for IPPB, and airway clearance (73 %) and repeated respiratory exacerbations (57 %) for IPV. The parents were the main carers performing the treatment at home., Conclusions: IPPB was the most prescribed technique. Diseases and initiation criteria are heterogeneous, underlining the need for studies validating the indications and settings of these techniques., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Iron oxide nanoparticles have received remarkable attention in different applications. For biomedical applications, they need to possess suitable core size, acceptable hydrodynamic diameter, high saturation magnetization, and reduced toxicity. Our aim is to control the synthesis parameters of nanostructured iron oxides in order to obtain magnetite nanoparticles in a single step, in environmentally friendly conditions, under inert gas atmosphere. The physical-chemical, structural, magnetic, and biocompatible properties of magnetite prepared by hydrothermal method in different temperature and pressure conditions have been explored. Magnetite formation has been proved by Fourier-transform infrared spectroscopy and X-ray diffraction characterization. It has been found that crystallite size increases with pressure and temperature increase, while hydrodynamic diameter is influenced by temperature. Magnetic measurements indicated that the magnetic core of particles synthesized at high temperature is larger, in accordance with the crystallite size analysis. Particles synthesized at 100 °C have nearly identical magnetic moments, at 20 × 10 3 μ B , corresponding to magnetic cores of 10-11 nm, while the particles synthesized at 200 °C show slightly higher magnetic moments (25 × 10 3 μ B ) and larger magnetic cores (13 nm). Viability test results revealed that the particles show only minor intrinsic toxicity, meaning that these particles could be suited for biomedical applications.

Cancer treatment by magneto-mechanical effect of particles (TMMEP) is a growing field of research. The principle of this technique is to apply a mechanical force on cancer cells in order to destroy them thanks to magnetic particles vibrations. For this purpose, magnetic particles are injected in the tumor or exposed to cancer cells and a low-frequency alternating magnetic field is applied. This therapeutic approach is quite new and a wide range of treatment parameters are explored to date, as described in the literature. This review explains the principle of the technique, summarizes the parameters used by the different groups and reports the main in vitro and in vivo results., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Aims: The objective of this study was to examine the association between the different patterns of left ventricular (LV) remodelling/hypertrophy on all-cause and cardiovascular mortality in patients with aortic stenosis (AS)., Methods and Results: In total, 747 consecutive patients (69 ± 14 years, 57% men) with AS and preserved LV ejection fraction were included in this study. According to LV mass index and relative wall thickness, patients were classified into four LV patterns: normal, concentric remodelling (CR), concentric hypertrophy (CH), and eccentric hypertrophy (EH). One hundred and sixteen patients (15%) had normal pattern, 66 (9%) had EH, 169 (23%) had CR, and 396 (53%) had CH. During a median follow-up of 6.4 years, 339 patients died (242 from cardiovascular causes). CH was associated with higher risk of all-cause mortality compared with the three other LV patterns (all P < 0.05). After multivariable adjustment, CH remained associated with higher risk of mortality (HR = 1.27, 95% CI 1.01-1.61, P = 0.046). There was a significant interaction (P < 0.05) between sex and CH with regards to the impact on mortality: CH was associated with worse outcome in women (P = 0.0001) but not in men (P = 0.22). In multivariable analysis, CH remained associated with higher risk of worse outcome in women (HR = 1.56, 95% CI 1.08-2.24, P = 0.018)., Conclusions: This study shows that CH was independently associated with increased risk of mortality in AS patients with preserved ejection fraction. This association was observed in women but not in men. The pattern of LV remodelling/hypertrophy should be integrated in the risk stratification process in patients with AS., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Background: The timing of mitral valve surgery in asymptomatic patients with primary mitral regurgitation (MR) is controversial. We hypothesized that the forward left ventricular (LV) ejection fraction (LVEF; ie, LV outflow tract stroke volume divided by LV end-diastolic volume) is superior to the total LVEF to predict outcomes in MR. The objective of this study was to examine the association between echocardiographic parameters of MR severity and LV function and outcomes in patients with MR., Methods and Results: The clinical and Doppler-echocardiographic data of 278 patients with ≥mild MR and no class I indication of mitral valve surgery at baseline were retrospectively analyzed. The primary study end point was the composite of mitral valve surgery or death. During a mean follow-up of 5.4±3.2 years, there were 147 (53%) events: 96 (35%) MV surgeries and 66 (24%) deaths. Total LVEF and global longitudinal strain were not associated with the occurrence of events, whereas forward LVEF ( P <0.0001) and LV end-systolic diameter ( P =0.0003) were. After adjustment for age, sex, MR severity, Charlson probability, coronary artery disease, and atrial fibrillation, forward LVEF remained independently associated with the occurrence of events (adjusted hazard ratio: 1.09, [95% confidence interval]: 1.02-1.17 per 5% decrease; P =0.01), whereas LV end-systolic diameter was not ( P =0.48)., Conclusions: The results of this study suggest that the forward LVEF may be superior to the total LVEF and LV end-systolic diameter to predict outcomes in patients with primary MR. This simple and easily measurable parameter may be useful to improve risk stratification and select the best timing for intervention in patients with primary MR., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Objective: The study purpose was to assess the usefulness of echocardiographic parameters of aortic stenosis (AS) severity and left ventricular (LV) systolic function to predict mortality in AS. The main hypothesis is that parameters of LV systolic function are the most important independent predictors of mortality, whereas parameters of stenosis severity are not., Methods: 1065 consecutive patients with AS referred to the echocardiography laboratory and meeting the inclusion/exclusion criteria were included and followed during 5.7 years. The end points were aortic valve replacement (AVR) (n=584), composite of AVR or death (n=932), all-cause mortality (n=550) and cardiovascular mortality (n=398)., Results: The most powerful echocardiographic predictors of valve-related events were parameters of AS severity, such as peak aortic jet velocity (VPeak), mean gradient (MG) and aortic valve area (AVA) (all p<0.001). Regarding mortality, the main predictors were LV ejection fraction (LVEF) and stroke volume index (SVi) (p<0.05). After multivariable adjustment, LVEF (p<0.001) and SVi (p=0.02) remained the only echocardiographic predictors of mortality, even after adjustment for symptomatic status. AVA was also associated with mortality, whereas VPeak and MG were not., Conclusions: The most powerful echocardiographic predictors of mortality are low LVEF and low flow, whereas AS severity parameters predict valve-related events but not overall mortality. Hence, low flow should be integrated in the risk stratification and therapeutic decision-making in patients with AS., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: Low flow (LF), defined as stroke volume index (SVi) <35 mL/m(2), prior to the procedure has been recently identified as a powerful independent predictor of early and late mortality in patients undergoing transcatheter aortic valve replacement (TAVR). The objectives of this study were to determine the evolution of SVi following TAVR and to assess the determinants and impact on mortality of early postprocedural SVi (EP-SVi)., Methods: We retrospectively analysed the clinical, Doppler echocardiographic and outcome data prospectively collected in 255 patients who underwent TAVR. Echocardiograms were performed before (baseline), within 5 days after procedure (early post procedure) and 6 months to 1 year following TAVR (late post procedure)., Results: Patients with EP-SVi <35 mL/m(2) (n=138; 54%) had increased mortality (HR 1.97, p=0.003) compared with those with EP-SVi ≥35 mL/m(2) (n=117; 46%). Furthermore, patients with baseline SVi (B-SVi) <35 mL/m(2) and EP-SVI ≥35 mL/m(2), that is, normalised flow, had better survival (HR 0.46, p=0.03) than those with both B-SVi and EP-SVi <35 mL/m(2), that is, persistent LF, and similar survival compared with those with both B-SVi and EP-SVi ≥35 mL/m(2), that is, maintained normal flow. In a multivariable model analysis, EP-SVi was independently associated with increased risk of mortality (HR 1.41 per 10 mL/m(2) decrease, p=0.03). The preprocedural/intraprocedural factors associated with lower EP-SVi were lower B-SVi (standardised β [β] 0.36, p<0.001) atrial fibrillation (β -0.13, p=0.02) and transapical approach (β -0.22, p<0.001)., Conclusions: The measurement of EP-SVi is useful to assess the immediate haemodynamic benefit of TAVR and to predict the risk of late mortality., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Epicutaneous immunotherapy is a developing technique, aiming at desensitizing patients with food allergy with less risks that oral ingestion or injection could generate. Several clinical trials have been performed and are currently running, in milk and peanut allergy, assessing the safety of the technique and its efficacy. Preclinical models indicate a major role in the mechanisms of desensitization, for example, Tregs and epigenetic modifications.

Background: The transthoracic echocardiographic (TTE) evaluation of the severity of residual aortic regurgitation (AR) following transcatheter aortic valve implantation (TAVI) has been controversial and lacks validation., Objectives: This study sought to compare TTE and cardiac magnetic resonance (CMR) for assessment of AR in patients undergoing TAVI with a balloon-expandable valve., Methods: TTE and CMR exams were performed pre-TAVI in 50 patients and were repeated postprocedure in 42 patients. All imaging data were analysed in centralised core laboratories., Results: The severity of native AR as determined by multiparametric TTE approach correlated well with the regurgitant volume and regurgitant fraction determined by CMR prior to TAVI (Rs=0.79 and 0.80, respectively; p<0.001 for both). However, after TAVI, the correlation between the prosthetic AR severity assessed by TTE and regurgitant volume and fraction measured by CMR was only modest (Rs=0.59 and 0.59, respectively; p<0.001 for both), with an underestimation of AR severity by TTE in 61.9% of patients (1 grade in 59.5%). The TTE jet diameter in parasternal view and the multiparametric approach (Rs=0.62 and 0.59, respectively; both with p<0.001) showed the best correlation with CMR regurgitant fraction post-TAVI. The circumferential extent of prosthetic paravalvular regurgitation showed a poor correlation with CMR regurgitant volume and fraction (Rs=0.32, p=0.084; Rs=0.36, p=0.054, respectively)., Conclusions: The severity of AR following TAVI with a balloon-expandable valve was underestimated by echocardiography as compared with CMR. The jet diameter, but not the circumferential extent of the leaks, and the multiparametric echocardiography integrative approach best correlated with CMR findings. These results provide important insight into the evaluation of AR severity post-TAVI., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: The operative risk of cardiac surgery is ascertained preoperatively on the basis of scores validated in multinational studies. However, the value they add to a simple bedside clinical evaluation (CE) remains controversial., Aims: To compare operative mortality (defined as death from all causes before the 31st postoperative day) predicted by CE with that predicted by additive and logistic EuroSCOREs, EuroSCORE II and Society of Thoracic Surgeons (STS), Ambler and age-creatinine-ejection fraction (ACEF) scores in patients undergoing aortic valve replacement (AVR) for severe aortic stenosis., Methods: Overall, 314 consecutive patients were included who underwent AVR between October 2009 and November 2011 (22% with coronary artery bypass graft); mean age 73.4 ± 9.7 years (29% aged>80 years). Based on CE, patients were divided into four predefined groups of increasing estimated mortality risk: I ≤ 3.9%; II 4-6.9%; III 7-9.9%; IV ≥ 10%. The positive and negative predictive values of the six scores and CE were compared., Results: The observed overall operative mortality was 5.7%. The distribution of the four predicted mortality groups by each score was highly variable. The positive predictive value, calculated for the 64 patients classified at highest risk by CE (groups III or IV) or each score, was 17.2% for EuroSCORE II, 14.1% for CE and STS scores, 10.9% for additive and logistic EuroSCOREs, 10.6% for ACEF and 10.2% for Ambler. The positive predictive value of each score in the low-risk groups (I and II) ranged from 2.8% to 4.4%., Conclusion: A simple bedside CE appears as reliable as the various established scores for predicting operative risk in patients undergoing surgical aortic valve replacement. The development and validation of more comprehensive risk stratification tools, including risk factors thus far neglected, seems warranted., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Objectives: The study sought to describe a specific syndrome characterized by isolated left bundle branch block (LBBB) and a history of progressive left ventricular (LV) dysfunction, successfully treated by cardiac resynchronization therapy (CRT)., Background: Isolated LBBB in animals causes cardiac remodeling due to mechanical dyssynchrony, reversible by biventricular stimulation. However, the existence of LBBB-induced cardiomyopathy in humans remains uncertain., Methods: Between 2007 and 2010, 375 candidates for CRT were screened and retrospectively included in this study if they met all criteria of a pre-defined syndrome, including: 1) history of typical LBBB for >5 years; 2) LV ejection fraction (EF) >50%; 3) decrease in LVEF to <40% and development of heart failure (HF) to NYHA functional class II to IV over several years; 4) major mechanical dyssynchrony; 5) no known etiology of cardiomyopathy; and 6) super-response to CRT with LVEF >45% and decrease in NYHA functional class at 1 year., Results: The syndrome was identified in 6 patients (1.6%), 50.5 years of age on average at the time of LBBB diagnosis. HF developed over a mean of 11.6 years. At the time of referral, Doppler echocardiograms showed major mechanical dyssynchrony at left atrioventricular, interventricular, and left intraventricular levels. During CRT, NYHA functional class decreased, LV dimensions normalized and mechanical dyssynchrony was nearly resolved in all patients, and mean LVEF increased from 31 ± 12% to 56 ± 8% (p = 0.027)., Conclusions: These observations support the existence of a specific LBBB-induced cardiomyopathy resolved by CRT. Its prevalence, time course, and risk factors need to be prospectively studied., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The objective of this study is to ascertain the effects of the left (LV) and right (RV) ventricular lead tip position in response to cardiac resynchronization therapy (CRT)., Background: The REVERSE randomized trial examined the effects of CRT in patients with asymptomatic or mildly symptomatic heart failure (HF)., Methods: We analysed data collected from the active group (CRT-ON) of REVERSE in whom the precise locations of the LV and RV ventricular lead tips were determined from postoperative chest roentgenograms as part of a prespecified sub-study. LV position was classified as lateral or non-lateral, and apical or non-apical. RV position was classified as apical or non-apical. Echocardiographic LV end-systolic volume index (LVESVi), QRS duration, and clinical outcomes at 12-24 months of follow-up were evaluated with respect to the lead tip position. The primary trial endpoint was the proportion of patients with a worsened HF clinical composite response, scored as improved, unchanged, or worsened., Results: Totally 346 patients included in this analysis were followed for a median of 12.6 months (interquartile range: 11.9-23.9 months). The proportion of worsened HF clinical composite response did not correlate with lead position, whereas a significantly greater decrease in the powered secondary endpoint of LVESVi was observed with the non-apical vs. the apical LV lead positions. CRT-paced QRS duration was significantly shorter than at baseline in patients with lateral vs. non-lateral LV position, as well non-apical vs. apical LV position. The incidence of composite endpoint of death and first hospitalization for HF was lower in the LV lateral than in the non-lateral (HR 0.44; 95% CI 0.19-0.99; P= 0.04), and in the LV non-apical than in the apical group (HR 0.27; 95% CI 0.11-0.63; P= 0.001). No significant differences were observed between RV apical and non-apical positions of the lead tip., Conclusions: A more favourable outcome of CRT with regard to LV reverse remodelling and the composite of time to death or first HF hospitalization was observed when the LV lead tip was implanted in the lateral wall, away from the apex, while the position of the RV lead tip was indifferent. The long-term change in QRS duration was significantly associated with the position of the LV lead tip. ClinicalTrials.gov Identifier: NCT00271154.

Objectives: To describe and analyze spontaneous reports of central nervous system (CNS) demyelinating disease including multiple sclerosis, following vaccination with GenHevac B vaccine, from 1989 to December 31, 1998., Methods: Descriptive analysis of adverse event reports in the vaccinated population, including the number of cases of CNS demyelinating disease, their frequencies, their dates of onset in relation to dates of report and their distribution according to age, sex and the number of injections. A Kaplan-Meier curve was used to analyze the time period between the last dose of vaccine and the onset of CNS demyelinating disease., Results: Overall, 187 cases of CNS demyelinating disease were spontaneously reported, (0.54 reports per 100,000 doses of GenHevac B distributed). The average time period between the occurring date of onset of the disease and its subsequent report was 24 months. The average age of onset was 31.7 years old and 73% of cases were women. The time between the last dose of vaccine and the onset of disease was regularly distributed from 1 day to 5 years (median: 60 days)., Conclusion: These results, together with available clinical, epidemiological data regarding multiple sclerosis, do not suggest a causal relationship between CNS demyelinating disease and vaccination with GenHevac B.