Archives of Cardiovascular Diseases最新文献

{"title":"Rationale and design of the FRENch CoHort of myocardial Infarction Evaluation (FRENCHIE) study","authors":"Alexandre Gautier ,&nbsp;Nicolas Danchin ,&nbsp;Gregory Ducrocq ,&nbsp;Alexandra Rousseau ,&nbsp;Yves Cottin ,&nbsp;Guillaume Cayla ,&nbsp;Fabrice Prunier ,&nbsp;Isabelle Durand-Zaleski ,&nbsp;Philippe Ravaud ,&nbsp;Denis Angoulvant ,&nbsp;Pierre Coste ,&nbsp;Gilles Lemesle ,&nbsp;Claire Bouleti ,&nbsp;Batric Popovic ,&nbsp;Emile Ferrari ,&nbsp;Johanne Silvain ,&nbsp;Olivier Dubreuil ,&nbsp;Thibault Lhermusier ,&nbsp;Pascal Goube ,&nbsp;François Schiele ,&nbsp;Tabassome Simon","doi":"10.1016/j.acvd.2024.04.004","DOIUrl":"10.1016/j.acvd.2024.04.004","url":null,"abstract":"<div><h3>Background</h3><p>Despite major advances in prevention and treatment, cardiovascular diseases – particularly acute myocardial infarction – remain a leading cause of death worldwide and in France. Collecting contemporary data about the characteristics, management and outcomes of patients with acute myocardial infarction in France is important.</p></div><div><h3>Aims</h3><p>The main objectives are to describe baseline characteristics, contemporary management, in-hospital and long-term outcomes of patients with acute myocardial infarction hospitalized in tertiary care centres in France; secondary objectives are to investigate determinants of prognosis (including periodontal disease and sleep-disordered breathing), to identify gaps between evidence-based recommendations and management and to assess medical care costs for the index hospitalization and during the follow-up period.</p></div><div><h3>Methods</h3><p>FRENCHIE (FRENch CoHort of myocardial Infarction Evaluation) is an ongoing prospective multicentre observational study (ClinicalTrials.gov Identifier: <span>NCT04050956</span><svg><path></path></svg>) enrolling more than 19,000 patients hospitalized for acute myocardial infarction with onset of symptoms within 48<!--> <!-->hours in 35 participating centres in France since March 2019. Main exclusion criteria are age<!--> <!-->&lt;<!--> <!-->18 years, lack of health coverage and procedure-related myocardial infarction (types 4a and 5). Detailed information was collected prospectively, starting at admission, including demographic data, risk factors, medical history and treatments, initial management, with prehospital care pathways and medication doses, and outcomes until hospital discharge. The follow-up period (up to 20 years for each patient) is ensured by linking with the French national health database (<em>Système national des données de santé</em>), and includes information on death, hospital admissions, major clinical events, healthcare consumption (including drug reimbursement) and total healthcare costs. FRENCHIE is also used as a platform for cohort-nested studies – currently three randomized trials and two observational studies.</p></div><div><h3>Conclusions</h3><p>This nationwide large contemporary cohort with very long-term follow-up will improve knowledge about acute myocardial infarction management and outcomes in France, and provide a useful platform for nested studies and trials.</p></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141143486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autonomic profiling in primary autonomic failure: Insights from 30 cases","authors":"Samah El-Mhadi ,&nbsp;Mustapha El Bakkali ,&nbsp;Najat Mouine ,&nbsp;Souad Aboudrar ,&nbsp;Halima Benjelloun ,&nbsp;Rokya Fellat","doi":"10.1016/j.acvd.2024.05.021","DOIUrl":"https://doi.org/10.1016/j.acvd.2024.05.021","url":null,"abstract":"<div><h3>Introduction</h3><p>Primary autonomic failure (PAF) is a progressive impairment of the autonomic nerve fibers concerning the two major components, sympathetic and parasympathetic. It is characterized by a combination of supine arterial hypertension (HT) and orthostatic hypotension (OH) without elevation of heart rate (HR).</p></div><div><h3>Objective</h3><p>To establish the autonomic profile of patients with PAF.</p></div><div><h3>Method</h3><p>Study design: a prospective study conducted in cardiology A department of Ibn Sina University Hospital Center, in collaboration with exercise physiology and autonomic nervous system team, from June 2022 to June 2023.</p><p>Inclusion criteria: patients with functional signs of PAF, with absence of neurological signs.</p><p>Exclusion criteria: patients with severe HT, secondary or complicated HT.</p><p>The cardiovascular autonomic testing included Deep Breathing (DB), Hand-Grip (HG), Mental Stress (MS) and orthostatic tests were performed.</p></div><div><h3>Results</h3><p>A total of 30 patients were included. The average age was of 53.2<!--> <!-->±<!--> <!-->6.4 years and 67% were females.</p><p>The results of cardiovascular autonomic tests were as follow: vagal response obtained during DB test was of 19.0%<!--> <!-->±<!--> <!-->4.8; vagal response and alpha peripheral sympathetic response obtained on HG test were of 7.3%<!--> <!-->±<!--> <!-->1.7 and 8.6%<!--> <!-->±<!--> <!-->1.4, respectively; alpha central sympathetic response and beta central sympathetic response obtained during MS test were of 7.9%<!--> <!-->±<!--> <!-->1.3 and 8.9%<!--> <!-->±<!--> <!-->1.1, respectively. Vagal response, alpha peripheral adrenergic sympathetic response and beta peripheral adrenergic sympathetic response obtained during the orthostatic test were of 7.2%<!--> <!-->±<!--> <!-->1.6, 6.1%<!--> <!-->±<!--> <!-->1.7and 7.4%<!--> <!-->±<!--> <!-->1.5, respectively.</p></div><div><h3>Conclusion</h3><p>Our study showed a significant vagal and sympathetic impairment, with severe orthostatic hypotension without elevation of heart rate, which could be responsible for syncope in the absence of neurological signs in patients with primary autonomic failure.</p></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141481764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FABP3 as a very early prognostic biomarker of ST-segment elevation myocardial infarction (STEMI): Kinetics matter","authors":"Bertrand Scheppler ,&nbsp;Ahmad Hayek ,&nbsp;Camille Brun ,&nbsp;Florentin Moulin ,&nbsp;Léa Azar ,&nbsp;Juliette Bourdin ,&nbsp;Simon Leboube ,&nbsp;Cyril Prieur ,&nbsp;Danka Tomasevic ,&nbsp;Nathalie Genot ,&nbsp;Eric Bonnefoy-Cudraz ,&nbsp;Sylvie Ducreux ,&nbsp;Nathan Mewton ,&nbsp;Gabriel Bidaux ,&nbsp;Melanie Paillard ,&nbsp;Claire Crola Da Silva ,&nbsp;Thomas Bochaton","doi":"10.1016/j.acvd.2024.05.030","DOIUrl":"https://doi.org/10.1016/j.acvd.2024.05.030","url":null,"abstract":"<div><h3>Introduction</h3><p>FABP3, a fatty acid-binding protein, is involved in intracellular fatty acid transport, predominantly expressed in cardiac cells. Its serum levels increase during myocardial infarction (MI) but its kinetics at the acute phase of MI is not known.</p></div><div><h3>Objective</h3><p>We explored whether the plasma level kinetics of FABP3 could predict the severity of MI.</p></div><div><h3>Method</h3><p>We prospectively enrolled 412 consecutive ST-elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI) in a prospective cohort. Blood samples were collected at 5 time points: admission, 4, 24, 48<!--> <!-->hours, and 1-month post-admission. FABP3 plasma levels were assessed using ELISA. Patients underwent cardiac magnetic resonance imaging (MRI) after one month. Clinical outcomes were prospectively recorded over 12<!--> <!-->months.</p></div><div><h3>Results</h3><p>The mean age of the studied population was 59<!--> <!-->±<!--> <!-->12<!--> <!-->years, with 55.6% having anterior MI. Median LVEF was 51% IQR [45–58]. FABP3 plasma levels reached a peak as early as admission and decreased from 18.5 [6.8–66.4] ng/mL at admission to 16.9 [7.7–37.8] ng/mL at 4<!--> <!-->h and gradually decreased to 4.3<!--> <!-->ng/mL [3.9–5.1] at 24<!--> <!-->h, 4.0<!--> <!-->ng/mL [3.7–4.4] at 48<!--> <!-->h and 3.8<!--> <!-->ng/mL [3.6–4.1] at 1 month (<span>Fig. 1</span>A). The FABP3 plasma level as early as admission and 4<!--> <!-->h was significantly correlated with infarct size (IS) (<em>r</em> <!-->=<!--> <!-->0.37, <em>P</em> <!-->&lt;<!--> <!-->0.0001 and <em>r</em> <!-->=<!--> <!-->0.66, <em>P</em> <!-->&lt;<!--> <!-->0.0001 respectively) and left ventricular ejection fraction (LVEF) assessed by MRI at 1-month (<em>r</em> <!-->=<!--> <!-->−0.33, <em>P</em> <!-->&lt;<!--> <!-->0.0001 and <em>r</em> <!-->=<!--> <!-->−0.58, <em>P</em> <!-->&lt;<!--> <!-->0.0001, respectively). Furthermore, patients with admission FABP3 plasma levels above the population median (18.5<!--> <!-->ng/L) were more likely to experience major adverse cardiovascular events (MACE) during the first 12<!--> <!-->months after STEMI [adjusted hazard ratio of 3.2 (1.72–6.26), <em>P</em> <!-->=<!--> <!-->0.01] (<span>Fig. 1</span>B). In a multivariable Cox regression analysis including age, gender, troponin peak, and TIMI flow grade post-PCI, admission serum FABP3 level remained associated with an increased risk of MACE over the 12-month follow-up (adjusted HR<!--> <!-->=<!--> <!-->2.3 (1.1–5.2), <em>P</em> <!-->=<!--> <!-->0.03).</p></div><div><h3>Conclusion</h3><p>Elevated circulating FABP3 levels upon admission for coronary angiography were independently associated with an increased risk of MACE in our population. The early measurement of FABP3 could be a valuable prognostic marker in STEMI patients, potentially guiding personalized therapeutic strategies in the future.</p></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141485182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of endothelial cell organisation on hiPSC-CM maturation in a cardiac micro-tissue model","authors":"Gabriel Friob,&nbsp;Jean-Sébastien Vartanian-Grimaldi,&nbsp;Pierre Joanne,&nbsp;Onnik Agbulut","doi":"10.1016/j.acvd.2024.05.012","DOIUrl":"https://doi.org/10.1016/j.acvd.2024.05.012","url":null,"abstract":"<div><h3>Introduction</h3><p>Over the past decade, the development of robust protocols for the generation of cardiomyocytes derived from human induced pluripotent stem cell (hiPSC-CMs) has considerably facilitated the study of genetic cardiomyopathies and the screening of new therapeutic molecules for cardiac diseases. One of the major limitations of this model is the lack of mature contractile function of hiPSC-CMs compared to adult human cardiomyocytes. Numerous studies have shown that the function of hiPSC-CMs can be improved by using multiple cardiac cell types in 3D co-culture to mimic the in vivo cell environment. However, the potential impact of the relative spatial organization of the different cell types inside the cardiac microtissue is still poorly understood.</p></div><div><h3>Objective</h3><p>The aim of this study is to evaluate the effect of endothelial cell organization on hiPSC-CM function within a cardiac microtissue model.</p></div><div><h3>Method</h3><p>After derivation of hiPSC-CMs from hiPSCs using a cardiac differentiation protocol, a 3D co-culture model called a “spheroid” is established by self-aggregation of different cardiac cell types (70% hiPSC-CM<!--> <!-->+<!--> <!-->15% cardiac fibroblasts<!--> <!-->+<!--> <!-->15% endothelial cells). Two different spheroid models with the same composition but with different organization (self-organized: endothelial cells homogeneously distributed or constrained: endothelial cells are concentrated to form a core at the center of the spheroid) will be functionally compared by assessing their contractility and kinetics of calcium transients. Molecular and cellular analyzes to identify the origin of the observed differences will also be performed using RT-qPCR and immunohistochemistry.</p></div><div><h3>Results</h3><p>Contractile analysis shows a significant increase in the amplitude of contraction of spheroids with the constrained organization (core of endothelial cells) to the self-organized spheroids (homogeneous distribution of cells). Differences in calcium kinetic parameters such as the time to reach the calcium peak or the time for calcium transient decay are also observed between the two conditions. Furthermore, immunohistochemistry and RT-qPCR analyses revealed an improved cell viability and maturation of hiPSC-CMs, demonstrating the positive effect of preforming an endothelial cell core on the function and maturation of this 3D model.</p></div><div><h3>Conclusion</h3><p>The development of this model highlights the important role of cell organization in the enhanced function of hiPSC-CMs enabled by 3D co-culture of cardiac cells.</p></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141481719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer therapy-related cardiac dysfunction (CTRCD) after radiation therapy for breast cancer: Results of the French BACCARAT study","authors":"Manoj Kumar François Honaryar ,&nbsp;Medea Locquet ,&nbsp;R.S. Allodji ,&nbsp;Gaelle Jimenez ,&nbsp;Olivier Lairez ,&nbsp;Loic Panh ,&nbsp;Jeremy Camilleri ,&nbsp;David Broggio ,&nbsp;Jean Ferrières ,&nbsp;F. De Vathaire ,&nbsp;Sophie Jacob","doi":"10.1016/j.acvd.2024.05.002","DOIUrl":"https://doi.org/10.1016/j.acvd.2024.05.002","url":null,"abstract":"<div><h3>Introduction</h3><p>Radiation therapy (RT) for breast cancer (BC) can result in a broad spectrum of cardiotoxicity including subtle cardiac dysfunction that can occur early after treatment. In 2022, the first European Society of Cardiology (ESC) guidelines in cardio-oncology defined asymptomatic cancer therapy-related cardiac dysfunction (CTRCD). This newly defined event has never been studied in BC patients treated with RT.</p></div><div><h3>Objective</h3><p>To evaluate early to mid-term asymptomatic CTRCD occurrence and to analyze the association with radiation-induced cardiac exposure.</p></div><div><h3>Method</h3><p>The prospective monocentric BACCARAT study included BC patients treated with RT without chemotherapy, aged 40–75<!--> <!-->years. Conventional and 2D Speckle tracking echocardiography was performed before, 6 and 24<!--> <!-->months after RT. The present analysis included all patients with left ventricle ejection fraction (LVEF) and global longitudinal strain (GLS) measurements available for the three-time points. Asymptomatic CTRCD, as defined in the latest ESC guidelines, combines information on LVEF and GLS decrease from baseline occurring 6 or 24<!--> <!-->months after RT. Whole heart, left ventricle (LV), and coronary arteries dose-volume parameters were considered to evaluate the impact of cardiac exposure on CTRCD.</p></div><div><h3>Results</h3><p>The study included 72 BC (of 59 left-sided BC) patients with a mean age of 58<!--> <!-->±<!--> <!-->8.2 years. A total of 32 (44%) patients developed any grade CTRCD during follow-up: 22 (31%) developed early dysfunction, and 14 (19%) developed midterm dysfunction with or without previous early dysfunction only in left BC patients. The cardiac doses were generally higher among patients with CTRCD rather than non-CTRCD. Significant dose-response relationships were observed between the risk of CTRCD and cardiac exposure, in particular LV exposure (OR for V2 LV dose<!--> <!-->=<!--> <!-->1.03 (1.00–1.06) <em>P</em> <!-->=<!--> <!-->0.01 and circumflex CX artery's mean dose OR<!--> <!-->=<!--> <!-->2.44 (1.26–4.74) <em>P</em> <!-->=<!--> <!-->0.008, D2 OR<!--> <!-->=<!--> <!-->1.79 (1.13–2.85) <em>P</em> <!-->=<!--> <!-->0.01 and V2 OR<!--> <!-->=<!--> <!-->1.02 (1.01–1.04) <em>P</em> <!-->=<!--> <!-->0.01. The results for the CX artery exposure were robust and significant after adjustment for classic cardiac risk factors (CVRF) and analyses according to the CTRCD grade; however, it did not remain significant for LV.</p></div><div><h3>Conclusion</h3><p>Our study suggests an association between specific cardiac structures and CTRCD 2<!--> <!-->years after BC RT. considering CVRF. However, given the limited number of patients, further research is needed to understand the early mechanisms of radiation-induced CTRCD.</p></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141481161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcatheter mitral valve repair by TEER device for recurrent eclipsed mitral regurgitation: A case report","authors":"Ulysse Maure ,&nbsp;Mohamad Ballout ,&nbsp;Amine Briedj ,&nbsp;Veronique Decalf","doi":"10.1016/j.acvd.2024.05.081","DOIUrl":"https://doi.org/10.1016/j.acvd.2024.05.081","url":null,"abstract":"<div><h3>Introduction</h3><p>Eclipsed mitral regurgitation (MR) is a rare entity of mitral regurgitation, characterized by a transient, reversible, and massive functional MR caused by a sudden coaptation defect without a reduction of the left ventricule ejection fraction. Even though ischemic hypotheses and variations in blood volume are potential causes, the exact pathophysiology of this rare occurrence remains unclear.</p></div><div><h3>Objective</h3><p>Several cases of eclipsed MR were reported in the literature with distinct therapeutic strategies that were associated with a significantly high risk of mortality following surgery. Only few cases treated by a transcatheter edge-to-edge repair (TEER) procedure was previously reported.</p></div><div><h3>Method</h3><p>We report the case of an 83-year-old woman with Eclipsed MR, that was successfully treated by a TEER procedure in our institution.</p></div><div><h3>Results</h3><p>An 83-year-old woman, with a known history of high blood pressure, dyslipidemia, and paroxysmal atrial fibrillation, presented with acute paroxysmal chest pain and dyspnea. A trans-thoracic echocardiogram (TTE) done a few months ago only showed a mild mitral regurgitation with a preserved ejection fraction. The patient was then transferred to the intensive cardiac care unit due to the high-risk setting of continuous heart failure, persistent AF, and chest pain. Increased troponin levels, and the suspicion of modification of repolarization on the ECG urged us to perform a coronary angiography that found one tight stenosis on the proximal left anterior descending artery, managed by one stent insertion.</p><p>After an initial clinic recovery, the patient suffered three severe episodes of cardiac decompensation with the need for catecholamines. During one of these episodes, TTE demonstrated a severe MR with regression on mild regurgitation at the same time (<span>Table 1</span>). To prevent recurrence in addition to the medical treatment, implantation of a TEER device on the mitral valve was successfully carried out, without complications and clinical recurrence of heart failure after six months of follow-up.</p></div><div><h3>Conclusion</h3><p>Severity of the eclipsed MR-related crises in this patient highlights the utmost importance of a rapid and accurate diagnosis to offer the earliest adapted management approaches to this uncommon cause of MR. Implantation of a TEER device seems proved to be a plausible and successful technique to manage eclipsed MR patients with reduced complications.</p></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141481177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phosphorylation of SERCA2 at the heart of cardioprotection in human-derived cardiomyocytes","authors":"Laura Boulogne ,&nbsp;Tanushri Dargar ,&nbsp;Camille Brun ,&nbsp;Christelle Leon ,&nbsp;Christophe Chouabe ,&nbsp;Hélène Thibault ,&nbsp;Gabriel Bidaux ,&nbsp;Laurent Sebbag ,&nbsp;Vincent Gache ,&nbsp;Ludovic Gomez","doi":"10.1016/j.acvd.2024.05.043","DOIUrl":"https://doi.org/10.1016/j.acvd.2024.05.043","url":null,"abstract":"<div><h3>Introduction</h3><p>Despite promising preclinical results targeting sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA2), clinical trials application remains limited, highlighting the urgency to develop suitable model reflecting clinical physiopathology. Recently, we discovered a new regulatory mechanism of SERCA2 based on serine 663-phosphorylation involved as a key regulator of Ca2+ homeostasis in several cell types (HEK, MEF and isolated mice cardiomyocytes).</p></div><div><h3>Objective</h3><p>To assess translational potential, we developed a human-induced pluripotent stem cell derived cardiomyocytes (hiPSC-CM) model focused on modulation of SERCA2 activity.</p></div><div><h3>Method</h3><p>hiPSC-derived cardiomyocytes were infected (6<!--> <!-->days, MOI 200 000) with the AAV9-Serca [WT], the AAV9-Serca2[S663A] phosphoresistant or the AAV9-Serca2[S663E] phosphomimetic mutants. For [Ca2+]ERexperiments, basal and refilling slope were measured in hiPSC-CM using D4ER Ca2+ probe. Cytosolic Ca2+ imaging was investigated using Fura2 probe (2<!--> <!-->μM). Cell viability was evaluated after 5<!--> <!-->h hypoxia (1%O₂) and 5<!--> <!-->h reoxygenation (H/R).</p></div><div><h3>Results</h3><p>In opposite to SERCA2[S663E] cells, the evaluation of SERCA2 activity revealed that SERCA2[S663A] hiPSC-CM displayed significantly increased ER Ca2+ refilling rate (+56%) and ER Ca2+ content (+66%) versus SERCA2[WT]. Interestingly, SERCA2[S663A] displayed a significant decreased cell death after H/R stress compared to SERCA2[WT]. Although, measuring of cytosolic Ca2+ transients in beating control hiPSC-CMs, there were no changes (peak amplitude 0.08<!--> <!-->μm, area under curve 0.04<!--> <!-->μm²) in all mutants due to ineffective infection.</p></div><div><h3>Conclusion</h3><p>Our results provide an essential regulatory mechanism of Ca2+ homeostasis and cell death, based on the phosphorylation state of SERCA2 in human cell types, notably hiPSC-CM. Although still requiring some adjustments, hiPSC-CM appear to be an essential model for translational research in the field of heart disease.</p></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141481078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Finerenone improves HFpEF in obese female mice and slows down its acceleration after a postmenopausal transition","authors":"Manon Monmirel ,&nbsp;Coralie Frimat ,&nbsp;Azzouz Charrabi ,&nbsp;Charles Fauvel ,&nbsp;Manon Valet ,&nbsp;Tony Noel ,&nbsp;Fabio Fernandes-Rosa ,&nbsp;Paul Mulder ,&nbsp;Jérémy Fauconnier ,&nbsp;Sheerazed Boulkroun ,&nbsp;Antoine Ouvrard-Pascaud","doi":"10.1016/j.acvd.2024.05.064","DOIUrl":"https://doi.org/10.1016/j.acvd.2024.05.064","url":null,"abstract":"<div><h3>Introduction</h3><p>Metabolic syndrome (MetS) and its related comorbidities significantly elevate the risk of heart failure with preserved ejection fraction (HFpEF), especially after menopause.</p></div><div><h3>Objective</h3><p>In obese mice with MetS and HFpEF, after 12<!--> <!-->weeks on a high-fat-sucrose (HFS) diet, we studied the effects of ovariectomy (Ovx) to induce a post-menopausal state. Ten days after surgery, we began finerenone treatment (1.5<!--> <!-->mg/kg/day, gavage) for either 4<!--> <!-->days (short-term) or 11<!--> <!-->weeks (long-term), ending after 14 or 25<!--> <!-->weeks of the HFS diet, respectively.</p></div><div><h3>Method</h3><p>The functional study of the left ventricle (LV) was carried out using ultrasound, MRI for coronary flow reserve measurements, and invasive hemodynamic. Exercise capacity was assessed by treadmill. LV remodeling was assessed by weighing and the measurement of mean cross-sectional area for hypertrophy, and Sirius red staining for fibrosis.</p></div><div><h3>Results</h3><p>After 14<!--> <!-->weeks on HFS diet, obese mice developed MetS and HFpEF, with LV compliance worsening rapidly after just two weeks of Ovx. Despite no LV hypertrophy at this stage, short-term Fine treatment allowed rapid recovery of compliance (LVEDPVR, mmHg/RVU: Ctrl 1.00<!--> <!-->±<!--> <!-->0.27, HFS 3.29<!--> <!-->±<!--> <!-->0.56*, HFS<!--> <!-->+<!--> <!-->Ovx 7.33<!--> <!-->±<!--> <!-->0.35*†, HFS<!--> <!-->+<!--> <!-->fine 1.13<!--> <!-->±<!--> <!-->0.35$, HFS<!--> <!-->+<!--> <!-->Ovx<!--> <!-->+<!--> <!-->fine 0.95<!--> <!-->±<!--> <!-->0.51$; * vs. Ctrl, † vs. non-OVX, $ vs. untreated). After 25<!--> <!-->weeks on HFS diet, obese female mice still had HFpEF, with impaired LV filling pressure and compliance, along with LV hypertrophy and fibrosis. Long-term Fine treatment improved diastolic parameters (LVEDPVR: Ctrl 1.51<!--> <!-->±<!--> <!-->0.15, HFS 6.90<!--> <!-->±<!--> <!-->0.79*, HFS<!--> <!-->+<!--> <!-->Ovx 6.82<!--> <!-->±<!--> <!-->0.95*, HFS<!--> <!-->+<!--> <!-->fine 2.38<!--> <!-->±<!--> <!-->0.26$, HFS<!--> <!-->+<!--> <!-->Ovx<!--> <!-->+<!--> <!-->fine 3.12<!--> <!-->±<!--> <!-->0.33$). MRI showed improved coronary flow reserve in Fine-treated post-menopausal obese mice (CFR, mL/min/g: HFS<!--> <!-->+<!--> <!-->Ovx 3.53<!--> <!-->±<!--> <!-->0.52, HFS<!--> <!-->+<!--> <!-->Ovx<!--> <!-->+<!--> <!-->fine 6.21<!--> <!-->±<!--> <!-->0.91$), but exercise capacity improved only in non-Ovx obese mice with finerenone. Finerenone more effectively reduced LV fibrosis in Ovx obese mice than in non-Ovx obese mice (collagen, %: Ctrl 7.0<!--> <!-->±<!--> <!-->0.4, HFS 9.3<!--> <!-->±<!--> <!-->0.3*, HFS<!--> <!-->+<!--> <!-->Ovx 9.8<!--> <!-->±<!--> <!-->0.6*, HFS<!--> <!-->+<!--> <!-->fine 6.45<!--> <!-->±<!--> <!-->0.5$, HFS<!--> <!-->+<!--> <!-->Ovx<!--> <!-->+<!--> <!-->fine 8.26<!--> <!-->±<!--> <!-->0.3#; # vs. non-OVX treated). Finally, larger cardiomyocyte size was observed in Ovx obese mice com","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141485128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alteration of transmural electrophysiological gradient in a rabbit model with a RyR2 mutation","authors":"Garance Gérard ,&nbsp;Francisco Alvarado ,&nbsp;Hector Valdivia ,&nbsp;Ana Maria Gomez Garcia ,&nbsp;Jean-Pierre Benitah ,&nbsp;Romain Perrier","doi":"10.1016/j.acvd.2024.05.092","DOIUrl":"https://doi.org/10.1016/j.acvd.2024.05.092","url":null,"abstract":"<div><h3>Introduction</h3><p>The cardiac Ca2+ release channel (RyR2) governs the release of Ca2+ from the sarcoplasmic reticulum, essential for cardiac muscle contraction. Naturally occurring mutations in RyR2 have been linked to several forms of cardiac arrhythmias (CPVT, ARVC) that require a vulnerable substrate characterized by structural or electrical abnormalities and an acute initiating event. Recently, a RyR2V2475F mutation has been identified post-mortem on a young boy whose death has been associated with arrhythmias, related to higher Ca2+ sensitivity of the mutated RyR2.</p></div><div><h3>Objective</h3><p>Our study aims to determine the arrhythmogenic mechanisms of the RyR2V2475F mutation by analyzing its impact on the ventricular action potential duration and Ca2+ homeostasis in a Knock-In rabbit model.</p></div><div><h3>Method</h3><p>Action Potentials (APs) were recorded using patch-clamp. Ca2+ sparks, SR Ca2+ load and Ca2+ transients have been analyzed using confocal microscopy. Ion channels expression was evaluated using RT-qPCR.</p></div><div><h3>Results</h3><p>With EGTA in the internal solution, APs of endocardial cardiomyocytes were shortened in RyR2V2475F mutants, with reduced APD20 and APD50 values compared to WT animals. This causes an inversion of the transmural repolarization gradient. The decrease of AP duration in endocardial cardiomyocytes was abolished in presence of BAPTA (a stronger Ca2+ chelator) in the internal solution. RyR2V2475F mutation did not alter K+ channel transcript levels. Ca2+ handling analysis showed a reduced diastolic Ca2+ sparks frequency, SR Ca2+ load and Ca2+ transients amplitudes.</p></div><div><h3>Conclusion</h3><p>These results suggest a role of altered Ca2+ handling in AP lengthening that could represent the vulnerable substrate that favors the apparition of arrhythmias.</p></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141485206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comite scientifique","authors":"","doi":"10.1016/S1875-2136(24)00201-8","DOIUrl":"https://doi.org/10.1016/S1875-2136(24)00201-8","url":null,"abstract":"","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1875213624002018/pdfft?md5=3ef558f3e4536abdf473af63742117a7&pid=1-s2.0-S1875213624002018-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141481159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}