25 research outputs found
Pathophysiologic risk stratification of chronic heart failure: coexisting left atrial and right ventricular damage and the role of pulmonary circulation
Abstract
Funding Acknowledgements
Type of funding sources: None.
Background
in heart failure with reduced ejection fraction (HFrEF) the chronic increase of filling pressures progressively involves left atrium (LA), pulmonary circulation (PC) and right ventricle (RV), leading to worse outcome.
Purpose
we investigated the prognostic impact of either isolate LA impairment, RV dysfunction combined with pulmonary hypertension, or both, in HFrEF, using basic and advanced echocardiography.
Methods
106 outpatients with HFrEF were enrolled. Exclusion criteria were primary lung disease, non-sinus rhythm, previous cardiac surgery, poor acoustic window. Clinical examination and basic echocardiography were performed. Speckle tracking analysis was used to measure peak atrial longitudinal strain (PALS) and a new marker of interaction between RV and PC: absolute free wall RV longitudinal strain(fwRVLS)/systolic pulmonary artery pressure(sPAP). Patients were followed for all-cause or cardiovascular death and heart failure (HF) hospitalization.
Results
of 84 eligible patients [mean age: 60.1 ± 11.5; 82% male, mean left ventricular ejection fraction (LV EF) 28 ± 5%], 48 reached the combined endpoint. Population was divided into 3 groups: Group 1 [PALS≥15 and fwRVLS/sPAP ≤ 0.5]; Group 2 [PALS ≤ 15 and fwRVLS/sPAP ≤ 0.5 or PALS≥15 and fwRVLS/sPAP≥0.5]; Group 3 [PALS ≤ 15 and fwRVLS/sPAP≥0.5]. Mean follow-up was 3.5 ± 0.3years. The increasing severity groups were associated with higher LA volume index (LAVI), New York Heart Association (NYHA) class, mitral regurgitation (MR) and tricuspid regurgitation (TR) grades, lower LV EF, LV global longitudinal strain (GLS), PALS, tricuspid annular plane systolic excursion (TAPSE), sPAP, fwRVLS and global RVLS(p < 0.0001). Reduced PALS and fwRVLS/sPAP were independent predictors of NYHA > 2 at univariate and multivariate analysis adjusted for age, sex, LV EF, and of any events with adjusted Cox models (Table 1). Kaplan-Meier curves showed a clear divergence between the groups for the prediction of the combined endpoint (Fig.1), cardiovascular death and HF hospitalization.
Conclusions
the combination of LA and RV damage could represent the transition point to end-stage HF, with considerably worse prognosis. Its assessment with PALS and fwRVLS/sPAP could help risk stratification of HFrEF patients in order to provide early treatment.
Table 1 Unadjusted hazard ratio [95% CI] Adjusted for GLS hazard ratio [95% CI] Adjusted for GLS, LAVi, TR, RVFAC hazard ratio [95% CI] Group 3 vs 1 10.61 [4.16-27.06], p < 0.0001 10.24 [3.49-30.02], p < 0.0001 9.54 [2.95-30.92], p = 0.0002 Group 3 vs 2 3.90 [1.92-7.93], p = 0.0002 3.82 [1.74-8.36], p = 0.0008 3.78 [1.66-8.61], p = 0.002 Group 2 vs 1 2.72 [1.03-7.20], p = 0.04 2.69 [0.99-7.25], p = 0.05 2.53 [0.84-7.58], p = 0.1 CI, confidence interval; EF, ejection fraction; GLS, global longitudinal strain;LAVI, left atrial volume index; MR, mitral regurgitation, TR, tricuspid regurgitation Abstract Figure. Fig.
Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells
Characterizing the multifaceted contribution of genetic and epigenetic factors to disease phenotypes is a major challenge in human genetics and medicine. We carried out high-resolution genetic, epigenetic, and transcriptomic profiling in three major human immune cell types (CD14 monocytes, CD16 neutrophils, and naive CD4 T cells) from up to 197 individuals. We assess, quantitatively, the relative contribution of -genetic and epigenetic factors to transcription and evaluate their impact as potential sources of confounding in epigenome-wide association studies. Further, we characterize highly coordinated genetic effects on gene expression, methylation, and histone variation through quantitative trait locus (QTL) mapping and allele-specific (AS) analyses. Finally, we demonstrate colocalization of molecular trait QTLs at 345 unique immune disease loci. This expansive, high-resolution atlas of multi-omics changes yields insights into cell-type-specific correlation between diverse genomic inputs, more generalizable correlations between these inputs, and defines molecular events that may underpin complex disease risk.This work was predominantly funded by the EU FP7 High Impact Project BLUEPRINT (HEALTH-F5-2011-282510) and the Canadian Institutes of Health Research (CIHR EP1-120608). The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no 282510 (BLUEPRINT), the European Molecular Biology Laboratory, the Max Planck society, the Spanish Ministry of Economy and Competitiveness, ‘Centro de Excelencia Severo Ochoa 2013-2017’, SEV-2012-0208 and Spanish National Bioinformatics Institute (INB-ISCIII) PT13/0001/0021 co-funded by FEDER "“Una Manera de hacer Europa”. D.G. is supported by a “la Caixa”-Severo Ochoa pre-doctoral fellowship, M.F. was supported by the BHF Cambridge Centre of Excellence [RE/13/6/30180], K.D. is funded as a HSST trainee by NHS Health Education England, S.E. is supported by a fellowship from La Caixa, V.P. is supported by a FEBS long-term fellowship and N.S.'s research is supported by the Wellcome Trust (Grant Codes WT098051 and WT091310), the EU FP7 (EPIGENESYS Grant Code 257082 and BLUEPRINT Grant Code HEALTH-F5-2011-282510) and the NIHR BRC. The Blood and Transplant Unit (BTRU) in Donor Health and Genomics is part of and funded by the National Institute for Health Research (NIHR) and is a partnership between the University of Cambridge and NHS Blood and Transplant (NHSBT) in collaboration with the University of Oxford and the Wellcome Trust Sanger Institute. The T-cell data was produced by the McGill Epigenomics Mapping Centre (EMC McGill). It is funded under the Canadian Epigenetics, Environment, and Health Research Consortium (CEEHRC) by the Canadian Institutes of Health Research and by Genome Quebec (CIHR EP1-120608), with additional support from Genome Canada and FRSQ. T.P. holds a Canada Research Chair
The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease
Many common variants have been associated with hematological traits, but identification of causal genes and pathways has proven challenging. We performed a genome-wide association analysis in the UK Biobank and INTERVAL studies, testing 29.5 million genetic variants for association with 36 red cell, white cell, and platelet properties in 173,480 European-ancestry participants. This effort yielded hundreds of low frequency (<5%) and rare (<1%) variants with a strong impact on blood cell phenotypes. Our data highlight general properties of the allelic architecture of complex traits, including the proportion of the heritable component of each blood trait explained by the polygenic signal across different genome regulatory domains. Finally, through Mendelian randomization, we provide evidence of shared genetic pathways linking blood cell indices with complex pathologies, including autoimmune diseases, schizophrenia, and coronary heart disease and evidence suggesting previously reported population associations between blood cell indices and cardiovascular disease may be non-causal.We thank members of the Cambridge BioResource Scientific Advisory Board and Management Committee for their support of our study and the National Institute for Health Research Cambridge Biomedical Research Centre for funding. K.D. is funded as a HSST trainee by NHS Health Education England. M.F. is funded from the BLUEPRINT Grant Code HEALTH-F5-2011-282510 and the BHF Cambridge Centre of Excellence [RE/13/6/30180]. J.R.S. is funded by a MRC CASE Industrial studentship, co-funded by Pfizer. J.D. is a British Heart Foundation Professor, European Research Council Senior Investigator, and National Institute for Health Research (NIHR) Senior Investigator. S.M., S.T, M.H, K.M. and L.D. are supported by the NIHR BioResource-Rare Diseases, which is funded by NIHR. Research in the Ouwehand laboratory is supported by program grants from the NIHR to W.H.O., the European Commission (HEALTH-F2-2012-279233), the British Heart Foundation (BHF) to W.J.A. and D.R. under numbers RP-PG-0310-1002 and RG/09/12/28096 and Bristol Myers-Squibb; the laboratory also receives funding from NHSBT. W.H.O is a NIHR Senior Investigator. The INTERVAL academic coordinating centre receives core support from the UK Medical Research Council (G0800270), the BHF (SP/09/002), the NIHR and Cambridge Biomedical Research Centre, as well as grants from the European Research Council (268834), the European Commission Framework Programme 7 (HEALTH-F2-2012-279233), Merck and Pfizer. DJR and DA were supported by the NIHR Programme ‘Erythropoiesis in Health and Disease’ (Ref. NIHR-RP-PG-0310-1004). N.S. is supported by the Wellcome Trust (Grant Codes WT098051 and WT091310), the EU FP7 (EPIGENESYS Grant Code 257082 and BLUEPRINT Grant Code HEALTH-F5-2011-282510). The INTERVAL study is funded by NHSBT and has been supported by the NIHR-BTRU in Donor Health and Genomics at the University of Cambridge in partnership with NHSBT. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health of England or NHSBT. D.G. is supported by a “la Caixa”-Severo Ochoa pre-doctoral fellowship
Natural-based nanocomposites for bone tissue engineering and regenerative medicine: a review
Tissue engineering and regenerative medicine has been providing exciting
technologies for the development of functional substitutes aimed to repair and
regenerate damaged tissues and organs. Inspired by the hierarchical nature of
bone, nanostructured biomaterials are gaining a singular attention for tissue
engineering, owing their ability to promote cell adhesion and proliferation, and
hence new bone growth, compared with conventional microsized materials.
Of particular interest are nanocomposites involving biopolymeric matrices and
bioactive nanosized fi llers. Biodegradability, high mechanical strength, and
osteointegration and formation of ligamentous tissue are properties required
for such materials. Biopolymers are advantageous due to their similarities with
extracellular matrices, specifi c degradation rates, and good biological performance.
By its turn, calcium phosphates possess favorable osteoconductivity,
resorbability, and biocompatibility. Herein, an overview on the available natural
polymer/calcium phosphate nanocomposite materials, their design, and properties
is presented. Scaffolds, hydrogels, and fi bers as biomimetic strategies for
tissue engineering, and processing methodologies are described. The specifi c
biological properties of the nanocomposites, as well as their interaction with
cells, including the use of bioactive molecules, are highlighted. Nanocomposites
in vivo studies using animal models are also reviewed and discussed.
The research leading to this work has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no REGPOT-CT2012-316331-POLARIS, and from QREN (ON.2 - NORTE-01-0124-FEDER-000016) cofinanced by North Portugal Regional Operational Program (ON.2 - O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund (ERDF)
Value of peak cardiac power output-to-left ventricular mass to risk stratify patients with chronic systolic heart failure
Value of peak cardiac power output-to-left ventricular mass to risk stratify patients with chronic systolic heart failur
Ultrasound assessment of left ventricular force-frequency relationship to risk stratify patients with advanced chronic systolic heart failure
Ultrasound assessment of left ventricular force-frequency relationship to risk stratify patients with advanced chronic systolic heart failur
Prognostic value of echo-derived peak cardiac power output-to-left ventricular mass compared to cardiopulmonary exercise testing in patients with chronic stable systolic heart failure
Prognostic value of echo-derived peak cardiac power output-to-left ventricular mass compared to cardiopulmonary exercise testing in patients with chronic stable systolic heart failur
The progression rate of aortic stenosis: key to tailoring the management and potential target for treatment
Aortic stenosis is the most frequent valvular disease to require intervention in the western world and has always been featured as a progressive disease. The rate of progression can be assessed by carefully performed Doppler echocardiography and can vary greatly between individuals with a profound impact on prognosis. Unfortunately, the determinants of disease progression had been insufficiently studied and remain challenging to define, particularly in the outpatient setting. Multiple factors have been proposed and tested, but at present, there are no proven therapies to slow the course of the stenotic process. Heart valve clinics may be particularly important to define the progression rate and tailor follow-up and management at an individual level. This review enlightens knowledge and gaps regarding the progression-rate of aortic valve stenosis, from the historical perspective to the molecular one
Recommended from our members
Sport PRactice and its Effects on aortic size and valve function in bicuspid Aortic valve Disease: a cross-sectional report from the SPREAD study.
OBJECTIVE: Concerns exist about the possible detrimental effects of exercise training on aortic size and valve function in individuals with bicuspid aortic valve (BAV). This multicentre international study aimed to determine the characteristics of aortic size and valve function in athletes versus non-athletes with BAV and athletes with tricuspid aortic valve (TAV). METHODS: We enrolled competitive athletes with BAV and age- and sex-matched athletes with TAV and non-athletes with BAV. We assessed valve function, aortic size and biventricular measures using echocardiography. Individuals with established moderate-severe AV stenosis, regurgitation or significant aortic dilation were excluded from the study. RESULTS: The study population comprised 504 participants: 186 competitive athletes with BAV (84% males; age 30±11 years), 193 competitive athletes with TAV and 125 non-athletes with BAV. The aortic annulus was greater in athletes with BAV than athletes with TAV and non-athletes with BAV (p<0.001). Both athletic and non-athletic individuals with BAV had greater sinuses of Valsalva, sino-tubular junction and ascending aorta diameters than athletes with TAV (p<0.001). However, no significant differences were found between athletes and non-athletes with BAV. Left ventricular index volumes and mass were greater in athletes with BAV than in the other two groups (p<0.001). Individuals with BAV (athletes and non-athletes) had greater mean gradients than TAV athletes. CONCLUSION: This multicentre international study demonstrates no differences between athletes with BAV and non-athletes with BAV regarding aortic valve function or aortic dimensions. However, athletes with BAV have larger aortic diameters and a relatively worse valvular function than athletes with TAV