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AIMS: Research on the pathophysiology of right ventricular (RV) failure has, in spite of the associated high mortality and morbidity, lagged behind compared to the left ventricle (LV).Previous work from our lab revealed that the embryonic basic helix-loop-helix transcription factor heart and neural crest derivatives expressed-2 (Hand2) is re-expressed in the adult heart and activates a 'fetal gene program' contributing to pathological cardiac remodeling under conditions of LV pressure overload. As such, ablation of cardiac expression of Hand2 conferred protection to cardiac stress and abrogated the maladaptive effects that were observed upon increased expression levels. In this study, we aimed to understand the contribution of Hand2 to RV remodeling in response to pressure overload induced by pulmonary artery banding (PAB). METHODS AND RESULTS: In the present study, Hand2F/F and MCM- Hand2F/F mice were treated with tamoxifen (control and knockout, respectively) and subjected to six weeks of RV pressure overload induced by PAB. Echocardiographic- and MRI-derived hemodynamic parameters as well as molecular remodeling were assessed for all experimental groups and compared to sham-operated controls. Six weeks after PAB, levels of Hand2 expression increased in the control banded animals but, as expected, remained absent in the knockout hearts. Despite the dramatic differences in Hand2 expression, pressure overload resulted in impaired cardiac function independently of the genotype. In fact, Hand2 depletion seems to sensitize the RV to pressure overload as these mice develop more hypertrophy and more severe cardiac dysfunction. Higher expression levels of HAND2 were also observed in RV samples of human hearts from patients with pulmonary hypertension. In turn, the LV of RV-pressure overloaded hearts was also dramatically affected as reflected by changes in shape, decreased LV mass and impaired cardiac function. RNA sequencing revealed a distinct set of genes that are dysregulated in the pressure-overloaded RV, compared to the previously described pressure-overloaded LV. CONCLUSIONS: Cardiac-specific depletion of Hand2 is associated with severe cardiac dysfunction in conditions of RV pressure overload. While inhibiting Hand2 expression can prevent cardiac dysfunction in conditions of LV pressure overload, the same does not hold true for conditions of RV pressure overload. This study highlights the need to better understand the molecular mechanisms driving pathological remodeling of the RV in contrast to the LV, in order to better diagnose and treat patients with RV or LV failure. TRANSLATIONAL PERSPECTIVE: RV failure associated with pulmonary hypertension reduces long-term survival rate to 55% within 3 years, suggesting that 3 years after diagnosis almost half of the patients will die. To revert these numbers an adequate RV-specific and, therefore, more efficient treatment is needed. Our work suggests that current therapies and potential mechanisms underlying LV failure may not be suitable for RV failure. While Hand2 deletion is favorable in LV response to stress, it is particularly detrimental in the RV under similar conditions, and thus, highlighting potential severe consequences of not differentiating therapeutic targets or treatment for RV or LV failure.

Randomized clinical trials initially used heart failure (HF) patients with low left ventricular ejection fraction (LVEF) to select study populations with high risk to enhance statistical power. However, this use of LVEF in clinical trials has led to oversimplification of the scientific view of a complex syndrome. Descriptive terms such as ‘HFrEF’ (HF with reduced LVEF), ‘HFpEF’ (HF with preserved LVEF), and more recently ‘HFmrEF’ (HF with mid-range LVEF), assigned on arbitrary LVEF cut-off points, have gradually arisen as separate diseases, implying distinct pathophysiologies. In this article, based on pathophysiological reasoning, we challenge the paradigm of classifying HF according to LVEF. Instead, we propose that HF is a heterogeneous syndrome in which disease progression is associated with a dynamic evolution of functional and structural changes leading to unique disease trajectories creating a spectrum of phenotypes with overlapping and distinct characteristics. Moreover, we argue that by recognizing the spectral nature of the disease a novel stratification will arise from new technologies and scientific insights that will shape the design of future trials based on deeper understanding beyond the LVEF construct alone. © The Author(s) 2019.

International audience; Silica monoliths loaded with hexacyanoferrate (HCF) nanoparticles were used in a continuous mode to selectively remove Cs+ from an aqueous saline solution. The decontamination and hydrodynamic efficiency was compared to other granularly supported HCF. A thermal treatment was then applied to transform the HCF functionalised monolith into the final 137Cs containment matrix.

International audience

International audience

International audience; abstract simple

The present study copes with the environmental impact assessment of municipal solid waste incineration bottom ash reused as aggregates in road construction. The methodology involves the following steps: characterization of bottom ashes (physical properties, chemistry and mineralogy), experiments at laboratory scale, field study and geochemical modeling. Quantitative data for trace elements in primary glasses obtained by Secondary Ions Mass Spectrometry (SIMS) microanalysis show that these glasses are likely a main sink for Zn, in the cemented calcite admixture, lead seems to be mainly sorbed on iron oxyhydroxides according to SMS imaging and Extended X-ray Absorption Fines Structure analysis (EXAFS). Except for SO4, low concentrations and alkalinity were measured in leachates from a 10 year-old road built with MSWI BA (fast attenuation during the fi rst years). No significant transformation of bottom ashes (such as an advanced carbonation state) was observed after 10 years of utilization. Lateral preferential flowpaths are probably responsible for the difference between alkaline pore water and diluted leachates. Based on characterization and experimental data, common model was built to simulate leaching and mineralogical evolutions using the transport reactive code CHESS-HYTEC. Simulations of batch and dynamic leaching tests, as well as of two roads (French and Swedish) built with bottom ashes show fair agreement with respect to the experimental data., L’évaluation du devenir des déchets à moyen et à long terme a été longtemps basée principalement sur la caractérisation des déchets par des essais de lixiviation. Le couplage entre la diffusion, la dissolution et la précipitation de phases solides, mais aussi de la sorption dans certains cas, des polluants inorganiques en compliquent souvent l’interprétation et donc l’extrapolation aux conditions réelles de sites. L’extrapolation des résultats de laboratoire aux conditions de sites - conditions caractérisées par des rapports solution sur solide bien plus bas, des géométries spécifiques et complexes, des schémas d’infi ltration cycliques, etc. - nécessite une démarche intégrant la modélisation géochimique couplée au transport. La présente étude concerne le comportement de mâchefers d’incinération des ordures ménagères (MIOM) dans le scénario de valorisation en sous-couche routière, l’objectif est d’en évaluer l’impact environnemental sur le sol sous-jacent et les eaux souterraines. La démarche mise en oeuvre associe des approches de caractérisation physicochimique et minéralogique, d’expérimentation à différentes échelles (lixiviation au laboratoire et suivi sur sites réels) en intégrant la modélisation hydro-géochimique.