Associations of Left Atrial Volume Index to Left Ventricular Ejection Fraction Ratio with Clinical Outcomes in Transthyretin Cardiac Amyloidosis.

Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) affects all cardiac chambers to cause left ventricular (LV) deformation as well as left atrial (LA) remodeling and functional impairment. We investigated the associations of the LA volume index (LAVI):LV ejection fraction (LVEF) ratio with the increased risk of death, heart transplant, or LV assist device implantation (LVAD) in patients with ATTR-CM.

Methods: This was a retrospective cohort study involving 69 heart failure (HF) patients with ATTR-CM at an academic medical center between 1 November 2008 and 31 March 2024.

Genetic ablation of Lmp2 increases the susceptibility for impaired cardiac function.

Proteasome degradation is an integral part of cellular growth and function. Proteasomal intervention may mitigate adverse myocardial remodeling, but is associated with the onset of heart failure. Previously, we have demonstrated that increasing abundance of cardiac Lmp2 and its incorporation into proteasome complexes is an endogenous mechanism for proteasome regulation during hypertrophic remodeling of the heart induced by chronic -adrenoreceptor stimulation.

Clinical, Echocardiographic, and Longitudinal Characteristics Associated With Heart Failure With Improved Ejection Fraction.

Heart failure with improved ejection fraction (HFimpEF) has better outcomes than HF with reduced EF (HFrEF). However, factors contributing to HFimpEF remain unclear. This study aimed to evaluate clinical and longitudinal characteristics associated with subsequent HFimpEF.

Clinical, Echocardiographic, and Longitudinal Characteristics Associated with Heart Failure with Improved Ejection Fraction.

Background: Heart failure (HF) with improved ejection fraction (HFimpEF) has better outcomes than HF with reduced ejection fraction (HFrEF). However, factors contributing to HFimpEF remain unclear. This study aimed to evaluate clinical and longitudinal characteristics associated with subsequent HFimpEF.

Remote monitoring titration clinic to implement guideline-directed therapy for heart failure patients with reduced ejection fraction: a pilot quality-improvement intervention.

Introduction: Guideline-directed medical therapy (GDMT) is the recommended treatment for heart failure with reduced ejection fraction (HFrEF). However, the implementation remains limited, with suboptimal use and dosing. The study aimed to assess the feasibility and effect of a remote monitoring titration program on GDMT implementation.

Unsupervised mRNA-seq classification of heart transplant endomyocardial biopsies.

Background: Endomyocardial biopsy (EMB) is currently considered the gold standard for diagnosing cardiac allograft rejection. However, significant limitations related to histological interpretation variability are well-recognized. We sought to develop a methodology to evaluate EMB solely based on gene expression, without relying on histology interpretation.

Insights and perspectives into clinical biomarker discovery in pediatric heart failure and congenital heart disease-a narrative review.

Background And Objective: Heart failure (HF) in the pediatric population is a multi-factorial process with a wide spectrum of etiologies and clinical manifestations, that are distinct from the adult HF population, with congenital heart disease (CHD) as the most common cause. CHD has high morbidity/mortality with nearly 60% developing HF during the first 12 months of life. Hence, early discovery and diagnosis of CHD in neonates is pivotal.

Cloud-Based Phrase Mining and Analysis of User-Defined Phrase-Category Association in Biomedical Publications.

The rapid accumulation of biomedical textual data has far exceeded the human capacity of manual curation and analysis, necessitating novel text-mining tools to extract biological insights from large volumes of scientific reports. The Context-aware Semantic Online Analytical Processing (CaseOLAP) pipeline, developed in 2016, successfully quantifies user-defined phrase-category relationships through the analysis of textual data. CaseOLAP has many biomedical applications.

A reference set of curated biomedical data and metadata from clinical case reports.

Clinical case reports (CCRs) provide an important means of sharing clinical experiences about atypical disease phenotypes and new therapies. However, published case reports contain largely unstructured and heterogeneous clinical data, posing a challenge to mining relevant information. Current indexing approaches generally concern document-level features and have not been specifically designed for CCRs.

A Metadata Extraction Approach for Clinical Case Reports to Enable Advanced Understanding of Biomedical Concepts.

Clinical case reports (CCRs) are a valuable means of sharing observations and insights in medicine. The form of these documents varies, and their content includes descriptions of numerous, novel disease presentations and treatments. Thus far, the text data within CCRs is largely unstructured, requiring significant human and computational effort to render these data useful for in-depth analysis.

Quantitative temporal analysis of protein dynamics in cardiac remodeling.

Cardiac remodeling (CR) is a complex dynamic process common to many heart diseases. CR is characterized as a temporal progression of global adaptive and maladaptive perturbations. The complex nature of this process clouds a comprehensive understanding of CR, but greater insight into the processes and mechanisms has potential to identify new therapeutic targets.

Clinical phenomapping and outcomes after heart transplantation.

Background: Survival after heart transplantation (HTx) is limited by complications related to alloreactivity, immune suppression, and adverse effects of pharmacologic therapies. We hypothesize that time-dependent phenomapping of clinical and molecular data sets is a valuable approach to clinical assessments and guiding medical management to improve outcomes.

Methods: We analyzed clinical, therapeutic, biomarker, and outcome data from 94 adult HTx patients and 1,557 clinical encounters performed between January 2010 and April 2013.

Integrated omics dissection of proteome dynamics during cardiac remodeling.

Transcript abundance and protein abundance show modest correlation in many biological models, but how this impacts disease signature discovery in omics experiments is rarely explored. Here we report an integrated omics approach, incorporating measurements of transcript abundance, protein abundance, and protein turnover to map the landscape of proteome remodeling in a mouse model of pathological cardiac hypertrophy. Analyzing the hypertrophy signatures that are reproducibly discovered from each omics data type across six genetic strains of mice, we find that the integration of transcript abundance, protein abundance, and protein turnover data leads to 75% gain in discovered disease gene candidates.

High-Resolution Mapping of Chromatin Conformation in Cardiac Myocytes Reveals Structural Remodeling of the Epigenome in Heart Failure.

Background: Cardiovascular disease is associated with epigenomic changes in the heart; however, the endogenous structure of cardiac myocyte chromatin has never been determined.

Methods: To investigate the mechanisms of epigenomic function in the heart, genome-wide chromatin conformation capture (Hi-C) and DNA sequencing were performed in adult cardiac myocytes following development of pressure overload-induced hypertrophy. Mice with cardiac-specific deletion of CTCF (a ubiquitous chromatin structural protein) were generated to explore the role of this protein in chromatin structure and cardiac phenotype.

Flow-Responsive Vascular Endothelial Growth Factor Receptor-Protein Kinase C Isoform Epsilon Signaling Mediates Glycolytic Metabolites for Vascular Repair.

Aims: Hemodynamic shear stress participates in maintaining vascular redox status. Elucidating flow-mediated endothelial metabolites enables us to discover metabolic biomarkers and therapeutic targets. We posited that flow-responsive vascular endothelial growth factor receptor (VEGFR)-protein kinase C isoform epsilon (PKCɛ)-6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) signaling modulates glycolytic metabolites for vascular repair.

HSPA5 Gene encoding Hsp70 chaperone BiP in the endoplasmic reticulum.

The HSPA5 gene encodes the binding immunoglobulin protein (BiP), an Hsp70 family chaperone localized in the ER lumen. As a highly conserved molecular chaperone, BiP assists in a wide range of folding processes via its two structural domains, a nucleotide-binding domain (NBD) and substrate-binding domain (SBD). BiP is also an essential component of the translocation machinery for protein import into the ER, a regulator for Ca homeostasis in the ER, as well as a facilitator of ER-associated protein degradation (ERAD) via retrograde transportation of aberrant proteins across the ER membrane.

A large dataset of protein dynamics in the mammalian heart proteome.

Protein stability is a major regulatory principle of protein function and cellular homeostasis. Despite limited understanding on mechanisms, disruption of protein turnover is widely implicated in diverse pathologies from heart failure to neurodegenerations. Information on global protein dynamics therefore has the potential to expand the depth and scope of disease phenotyping and therapeutic strategies.

The human cardiac and skeletal muscle proteomes defined by transcriptomics and antibody-based profiling.

Background: To understand cardiac and skeletal muscle function, it is important to define and explore their molecular constituents and also to identify similarities and differences in the gene expression in these two different striated muscle tissues. Here, we have investigated the genes and proteins with elevated expression in cardiac and skeletal muscle in relation to all other major human tissues and organs using a global transcriptomics analysis complemented with antibody-based profiling to localize the corresponding proteins on a single cell level.

Results: Our study identified a comprehensive list of genes expressed in cardiac and skeletal muscle.

Spatial and temporal dynamics of the cardiac mitochondrial proteome.

Mitochondrial proteins alter in their composition and quantity drastically through time and space in correspondence to changing energy demands and cellular signaling events. The integrity and permutations of this dynamism are increasingly recognized to impact the functions of the cardiac proteome in health and disease. This article provides an overview on recent advances in defining the spatial and temporal dynamics of mitochondrial proteins in the heart.

Isoflurane protects the myocardium against ischemic injury via the preservation of mitochondrial respiration and its supramolecular organization.

Background: Isoflurane has been demonstrated to limit myocardial ischemic injury. This effect is hypothesized to be mediated in part via effects on mitochondria. We investigated the hypothesis that isoflurane maintains mitochondrial respiratory chain functionality, in turn limiting mitochondrial damage and mitochondrial membrane disintegration during myocardial ischemic injury.

Characterization of human plasma proteome dynamics using deuterium oxide.

Purpose: High-throughput quantification of human protein turnover via in vivo administration of deuterium oxide ((2) H2 O) is a powerful new approach to examine potential disease mechanisms. Its immediate clinical translation is contingent upon characterizations of the safety and hemodynamic effects of in vivo administration of (2) H2 O to human subjects.

Experimental Design: We recruited ten healthy human subjects with a broad demographic variety to evaluate the safety, feasibility, efficacy, and reproducibility of (2) H2 O intake for studying protein dynamics.

THY-1 receptor expression differentiates cardiosphere-derived cells with divergent cardiogenic differentiation potential.

Despite over a decade of intense research, the identity and differentiation potential of human adult cardiac progenitor cells (aCPC) remains controversial. Cardiospheres have been proposed as a means to expand aCPCs in vitro, but the identity of the progenitor cell within these 3D structures is unknown. We show that clones derived from cardiospheres could be subdivided based on expression of thymocyte differentiation antigen 1 (THY-1/CD90) into two distinct populations that exhibit divergent cardiac differentiation potential.