Persistent disabilities 28 months after COVID-19 hospitalisation, a prospective cohort study.

Background: Limited data are available on long-term respiratory disabilities in patients following acute COVID-19.

Patients And Methods: This prospective, monocentric, observational cohort study included patients admitted to our hospital with acute COVID-19 between 12 March and 24 April 2020. Clinical, functional and radiological data were collected up to 28 months after hospital discharge.

Repression by SNAIL Results in ECM Remodeling in Genetic Risk for Vascular Diseases.

Background: Genome-wide association studies implicate common genetic variations in the (low-density lipoprotein receptor-related protein 1 gene) locus at risk for multiple vascular diseases and traits. However, the underlying biological mechanisms are unknown.

Methods: Fine mapping analyses included Bayesian colocalization to identify the most likely causal variant.

Rod-shaped micropatterning enhances the electrophysiological maturation of cardiomyocytes derived from human induced pluripotent stem cells.

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) offer great potential for drug screening and disease modeling. However, hiPSC-CMs remain immature compared to the adult cardiac cells. Cardiomyocytes isolated from adult human hearts have a typical rod-shaped morphology.

An update on oral antiplatelet drug interactions with proton pump inhibitors: what are the risks?

Introduction: Aspirin and anti-P2Y12 are widely prescribed in cardiovascular patients, often in combination with proton pump inhibitors (PPIs) to limit the risk of upper gastrointestinal bleedings. The potential interaction between PPIs and antiplatelet agents has been widely discussed, but doubts remain as to whether PPIs may reduce the cardiovascular protection provided by aspirin, prasugrel, ticagrelor, and clopidogrel.

Areas Covered: Many pharmacokinetic (PK) and pharmacodynamic (PD) studies have confirmed the interaction, especially between PPIs and clopidogrel, but with uncertain consequences on clinical outcomes.

Adverse myocardial and vascular side effects of immune checkpoint inhibitors: a prospective multimodal cardiovascular assessment.

Background: Immune checkpoint inhibitors (ICIs) can induce cardiovascular toxicities.

Objectives: To prospectively assess the incidence of major cardiovascular events (MACE) on ICIs in solid cancer patients: myocarditis, pericarditis, acute coronary syndrome, heart failure, high-degree conduction abnormalities or sustained ventricular arrhythmias, or cardiovascular death at 6 weeks (early MACE), including asymptomatic clinical changes by an independent adjudication committee using current recommended diagnostic criteria. The secondary objective was the incidence of the above-mentioned events adding atrial fibrillation (AF) at 6 months (late MACE).

CAVIN1-Mediated hERG Dynamics: A Novel Mechanism Underlying the Interindividual Variability in Drug-Induced Long QT.

Background: Drug-induced QT prolongation (diLQT) is a feared side effect that could expose susceptible individuals to fatal arrhythmias. The occurrence of diLQT is primarily attributed to unintended drug interactions with cardiac ion channels, notably the hERG (human ether-a-go-go-related gene) channels that generate the delayed-rectifier potassium current (I) and thereby regulate the late repolarization phase. There is an important interindividual susceptibility to develop diLQT, which is of unknown origin but can be reproduced in patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs).

A versatile high-throughput assay based on 3D ring-shaped cardiac tissues generated from human induced pluripotent stem cell-derived cardiomyocytes.

We developed a 96-well plate assay which allows fast, reproducible, and high-throughput generation of 3D cardiac rings around a deformable optically transparent hydrogel (polyethylene glycol [PEG]) pillar of known stiffness. Human induced pluripotent stem cell-derived cardiomyocytes, mixed with normal human adult dermal fibroblasts in an optimized 3:1 ratio, self-organized to form ring-shaped cardiac constructs. Immunostaining showed that the fibroblasts form a basal layer in contact with the glass, stabilizing the muscular fiber above.

Association of Impaired Left Ventricular Mitral Filling from 4D Flow Cardiac MRI and Prognosis of Hypertrophic Cardiomyopathy.

Purpose To investigate whether the peak early filling rate normalized to the filling volume (PEFR/FV) estimated from four-dimensional (4D) flow cardiac MRI may be used to assess impaired left ventricular (LV) filling and predict clinical outcomes in individuals with hypertrophic cardiomyopathy (HCM). Materials and Methods Cardiac MRI with a 4D flow sequence and late gadolinium enhancement (LGE), as well as echocardiography, was performed in 88 individuals: 44 participants with HCM from a French prospective registry (ClinicalTrials.gov; NCT01091480) and 44 healthy volunteers matched for age and sex.

hsa-miR-548v controls the viscoelastic properties of human cardiomyocytes and improves their relaxation rates.

The impairment of left ventricular (LV) diastolic function with an inadequate increase in myocardial relaxation velocity directly results in lower LV compliance, increased LV filling pressures, and heart failure symptoms. The development of agents facilitating the relaxation of human cardiomyocytes requires a better understanding of the underlying regulatory mechanisms. We performed a high-content microscopy-based screening in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) using a library of 2,565 human miRNA mimics and measured relaxation kinetics via high-computing analyses of motion movies.

Circadian rhythm and circulating cell-free DNA release on healthy subjects.

In the last decade, clinical studies have investigated the clinical relevance of circulating cell-free-DNA (ccfDNA) as a diagnostic and prognosis tool in various diseases including cancers. However, limited knowledge on ccfDNA biology restrains its full development in the clinical practice. To improve our understanding, we evaluated the impact of the circadian rhythm on ccfDNA release in healthy subjects over a 24-h period.

Actin-microtubule cytoskeletal interplay mediated by MRTF-A/SRF signaling promotes dilated cardiomyopathy caused by LMNA mutations.

Mutations in the lamin A/C gene (LMNA) cause dilated cardiomyopathy associated with increased activity of ERK1/2 in the heart. We recently showed that ERK1/2 phosphorylates cofilin-1 on threonine 25 (phospho(T25)-cofilin-1) that in turn disassembles the actin cytoskeleton. Here, we show that in muscle cells carrying a cardiomyopathy-causing LMNA mutation, phospho(T25)-cofilin-1 binds to myocardin-related transcription factor A (MRTF-A) in the cytoplasm, thus preventing the stimulation of serum response factor (SRF) in the nucleus.

Novel Cardiokine GDF3 Predicts Adverse Fibrotic Remodeling After Myocardial Infarction.

Background: Myocardial infarction (MI) induces a repair response that ultimately generates a stable fibrotic scar. Although the scar prevents cardiac rupture, an excessive profibrotic response impairs optimal recovery by promoting the development of noncontractile fibrotic areas. The mechanisms that lead to cardiac fibrosis are diverse and incompletely characterized.

[Integrins in cardiac fibrosis].

For the last 20 years, integrins have been a therapeutic target of interest in the treatment of fibrotic diseases, particularly regarding the integrins of the αV family. Initially developed as anti-cancer drugs but with modest benefits, inhibitors of integrins (such as the anti-αV cilengitide) have shown interesting anti-fibrotic effects in different organs including the heart. Cardiac fibrosis is defined as an accumulation of stiff extracellular matrix in the myocardium, and ultimately leads to heart failure, one of the leading causes of mortality worldwide.