Archives of Cardiovascular Diseases最新文献

{"title":"CPVT-related arrhythmogenic mechanisms: Ca2+-induced transmural electrophysiological gradient alteration in a RyR2-V2475F rabbit model","authors":"Garance Gérard ,&nbsp;Alvarado Francisco ,&nbsp;Zheng Jingjing ,&nbsp;Valdivia Héctor ,&nbsp;Ana Maria Gomez Garcia ,&nbsp;Jean-Pierre Benitah ,&nbsp;Romain Perrier","doi":"10.1016/j.acvd.2025.03.087","DOIUrl":"10.1016/j.acvd.2025.03.087","url":null,"abstract":"<div><h3>Introduction</h3><div>Inherited stress-induced ventricular arrhythmia, such as catecholaminergic polymorphic ventricular tachycardia (CPVT), is typically linked to excessive diastolic Ca2+ release from the cardiac sarcoplasmic reticulum (SR) via the ryanodine receptor (RyR2), triggering Na+/Ca2+ exchanger activity and delayed afterdepolarizations. However, altered Ca2+ release may also influence sarcolemmal ionic conductance, shaping cardiac electrical properties.</div></div><div><h3>Objective</h3><div>We investigated the impact of the RyR2-V2475F, using a rabbit knock-in model to determine the underlying arrhythmogenic mechanisms of this mutation.</div></div><div><h3>Method</h3><div>Action Potentials (APs) and Ca2+ currents (ICaL) were recorded using patch-clamp on left ventricle cardiomyocytes. Ca2+ sparks, SR Ca2+ load and Ca2+ transients were analyzed using confocal microscopy. Ion channels expression was studied using Western-Blotting.</div></div><div><h3>Results</h3><div>Analysis of intracellular Ca2+ homeostasis revealed that Ca2+ transient amplitude was reduced, correlating with smaller SR Ca2+ load in isolated ventricular RyR2-V2475F± cardiomyocytes compared to WT. This could be dependent on the activity of RyR2, as we found that the SR Ca2+ leak was increased. Nevertheless, the leak was mostly undetectable, as Ca2+ sparks frequency was depressed. These alterations were associated with a reduced window L-type Ca2+ current contributing to SR Ca2+ unloading in RyR2-V2475F± cardiomyocytes. Additionally, we noted a shortening of action potential duration of endocardial cardiomyocytes from RyR2-V2475F± rabbits. The resulting inversion of the transmural repolarization gradient was abolished in the presence of BAPTA, suggestive of a Ca2<!--> <!-->+<!--> <!-->-dependent effect, and could represent a vulnerable substrate that favors the appearance of arrhythmias. Indeed, RyR2-V2475F± rabbits developed a CPVT-like phenotype under pharmacological stress challenge. Interestingly, this phenotype was more pronounced in males than in females, consistent with a lesser impact on APs and ICaL of V2475F± in female animals.</div></div><div><h3>Conclusion</h3><div>Using a rabbit RyR2-V2475F model, we uncovered a potential new mechanism for CPVT-related arrhythmias, defined by a differential impact on AP duration between endocardium and epicardium, leading to a loss of an important protection mechanism against arrhythmias.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Pages S214-S215"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099565","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":"GRK2 inhibition by paroxetine prevents intermittent hypoxia-induced worsening of ischemic cardiomyopathy","authors":"Emma Billoir ,&nbsp;Stephanie Paradis ,&nbsp;Maximin Détrait ,&nbsp;Guillaume Vial ,&nbsp;Sophie Bouyon ,&nbsp;Boutin-Paradis Antoine ,&nbsp;Fabien Hubert ,&nbsp;Francesca Rochais ,&nbsp;Bilgehan Ozcan ,&nbsp;Britanny Blachot-Minassian ,&nbsp;Jean-Louis Pépin ,&nbsp;Elise Belaidi ,&nbsp;Claire Arnaud","doi":"10.1016/j.acvd.2025.03.042","DOIUrl":"10.1016/j.acvd.2025.03.042","url":null,"abstract":"<div><h3>Introduction</h3><div>Patients with obstructive sleep apnea (OSA) exhibit poor prognosis after myocardial infarction (MI). Intermittent hypoxia (IH), the hallmark feature of OSA, promotes sympathetic hyperactivity and systemic insulin resistance, and has been identified as a major contributor to post-MI cardiac remodeling and contractile dysfunction.</div></div><div><h3>Objective</h3><div>We hypothesize that sympathetic hyperactivity and metabolic alterations induced by IH participate in the aggravation of ischemic cardiomyopathy via activation of G protein-coupled receptors kinase (GRK2), known to be involved in adrenergic desensitization. To investigate the detrimental role of GRK2, we used paroxetine, described as a specific GRK2 inhibitor.</div></div><div><h3>Method</h3><div>MI is induced in C57bl6 mice by permanent ligation of the left coronary artery. Mice are then randomized to IH (21–5% FiO₂, 60 s cycle, 8<!--> <!-->h/day) or normoxia (N) for up to 6 weeks. After two weeks exposure, mice are treated with a GRK2 inhibitor, paroxetine (5<!--> <!-->mg/kg/d), or 25% DMSO (Alzet® pumps). Longitudinal follow-up of mice includes evaluation of sympathetic activity (spectral analysis of heart rate variability (HRV), systemic insulin sensitivity (dynamic insulin tolerance test) and determination of cardiac function/remodeling (echocardiography). At the end of the protocol, cardiac interstitial fibrosis and hypertrophy are evaluated by RT-qPCR and histology (Sirius Red and WGA staining). Assessment of insulin signaling pathway is performed by Western blot 15<!--> <!-->min after injection of NaCl or insulin (0,5<!--> <!-->UI/kg).</div></div><div><h3>Results</h3><div>Compared to N condition, IH worsens post-MI contractile dysfunction (i.e. ejection fraction), which is prevented by paroxetine treatment. Whereas IH does not induce cardiomyocyte hypertrophy, it results in increased cardiac interstitial fibrosis and apoptosis, which are limited by paroxetine. Our results evidence an IH-induced sympathetic overactivity in MI mice [i.e. increase in LF (Low Frequencies), derived from HRV analysis]. Paroxetine abolishes the increase in LF in MI-IH condition and restores mRNA expression of β1 and β2 adrenergic receptors. Finally, IH induces post-MI systemic insulin resistance compared to MI-N condition, which is prevented by paroxetine. This beneficial effect of paroxetine could result from improvement of insulin signaling in liver and muscle of MI-IH mice (pIRβ &amp; pAKT).</div></div><div><h3>Conclusion</h3><div>Inhibition of GRK2 by paroxetine limits IH-induced worsening of ischemic cardiomyopathy, by limiting both cardiac sympathetic hyperactivity and systemic insulin resistance.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Page S191"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099562","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":"Mesp1 and Hes1 interplay controls early cardiac progenitor cell specification","authors":"Sinem Inal,&nbsp;Fabienne Lescroart,&nbsp;Francesca Rochais","doi":"10.1016/j.acvd.2025.03.035","DOIUrl":"10.1016/j.acvd.2025.03.035","url":null,"abstract":"<div><h3>Introduction</h3><div>Cardiac progenitors (CPs) arise early during gastrulation. CPs express transcription factor Mesp1 and contribute to all cardiac territories. Alteration in CP specification or migration leads to congenital heart defects (CHDs) affecting 1% of live births. We uncovered Mesp1 as a master regulator of early cardiovascular specification and differentiation (Lescroart et al., Science 2018; Lin et al., Nat Cell Biol 2022), and recently identified a crucial role for transcriptional repressor Hes1 in CP deployment (Rammah et al., Circ Res 2022). Indeed, Hes1 deletion results in embryonic lethality due to CHDs. Interestingly, Hes1 conditional deletion in Mesp1 lineage recapitulates the heart defects observed in Hes1 null embryos.</div></div><div><h3>Objective</h3><div>To investigate the mechanism of early CP specification by exploring Mesp1 and Hes1 possible interplay.</div></div><div><h3>Method</h3><div>In vitro mouse gastrulation model, gastruloid and mouse embryos were used to reveal expression levels and patterns of Mesp1 and Hes1 using fluorescent in situ hybridization technique, RNAscope. RNAseq and Chip-seq experiments were performed on Mesp1 gain-of-function (GOF) mESC line. ScRNAseq analysis was performed during gastruloid culture.</div></div><div><h3>Results</h3><div>RNAscope on mouse embryos revealed differential Hes1 expression during gastrulation. While Hes1 expression is high in FHF progenitors, starts to decline in SHF progenitors. RNAseq and Chip-seq data using Mesp1 GOF mESCs has shown downregulation of Hes1 by Mesp1. Using Mesp1 mutant embryos, we showed increased Hes1 expression in mesoderm supporting the previous data. ScRNAseq on gastruloids revealed coexpression of Mesp1 and Hes1 in CP subpopulations. We reproduced these results with RNAscope and uncovered similar expression patterns in different CPs that of embryos. Hes1 expression is detected in Hand1+ FHF progenitors and downregulated in Foxc2+ SHF progenitors. These results validate our in vivo and in vitro models and point out a role for Hes1 in early heart development that has not been reported.</div></div><div><h3>Conclusion</h3><div>Our data strongly support a role for Mesp1-Hes1 interplay in the regulation of early CP specification.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Page S188"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099591","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":"Optimizing prehospital ST-segment elevation myocardial infarction pathways, medical dispatch types and acute management times: A French regional registry study.","authors":"Emilie Lesaine, Sahal Miganeh-Hadi, Mathilde Borg, Laura Cetran, Florence Saillour-Glénisson, Catherine Pradeau","doi":"10.1016/j.acvd.2025.04.052","DOIUrl":"https://doi.org/10.1016/j.acvd.2025.04.052","url":null,"abstract":"<p><strong>Background: </strong>Efficient management of emergency medical services is crucial, particularly during dispatch, to direct patients with ST-segment elevation myocardial infarction (STEMI) to the fastest medical intensive care unit pathway, bypassing emergency departments (EDs) at hospitals capable and incapable of percutaneous coronary intervention (PCI). A detailed analysis of emergency pathways may reveal key actions to improve patient care and outcomes.</p><p><strong>Aim: </strong>To describe the initial STEMI pathways, with a focus on dispatch management, acute management times and revascularization strategies for each pathway: medical intensive care unit; ED at PCI-capable hospital; and ED at PCI-incapable hospital.</p><p><strong>Methods: </strong>Multicentre retrospective study of all adult patients with STEMI diagnosed by emergency physicians within 24hours of symptom onset, and managed in any of the 19 medical intensive care units, seven PCI-capable hospitals and 25 PCI-incapable hospitals in the Aquitaine region from 1st January 2017 to 31st December 2021. The primary endpoint was the proportion of patients who missed the fastest pathway because of mistriage. The secondary endpoints focused on time intervals from symptom onset to balloon inflation.</p><p><strong>Results: </strong>The study sample comprised 8344 patients: 57% (95% confidence interval [CI] 56-58%) followed the fastest pathway; and 21% (95% CI 20-22%) missed it because of mistriage. The median (interquartile range) time spent in the ED was 78 (48-150) minutes at PCI-capable hospitals and 109 (71-178) minutes at PCI-incapable hospitals. Only 11% (95% CI 10-12%) of patients managed in EDs at PCI-incapable hospitals received fibrinolysis, and 79% (95% CI 76-82%) exceeded the recommended 120minutes from first medical contact to balloon for the primary PCI strategy.</p><p><strong>Conclusions: </strong>These findings should prompt French policymakers to improve the accuracy of dispatch and develop specific STEMI networks in EDs. Time lost in EDs or because of mistriage represents a considerable loss of opportunity for patients. The role of fibrinolysis should be reconsidered.</p>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227739","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":"Erythropoietin recapitulates ultrasound-assessed hemodynamic and morphological features of hypoxia-induced pulmonary hypertension in mice","authors":"Ghina Bouabout ,&nbsp;Julien Becker ,&nbsp;Emilie Peter-Thiebaut ,&nbsp;Mégane Denu ,&nbsp;Hugues Jacobs ,&nbsp;Benoit Petit Demoulière ,&nbsp;Yann Herault ,&nbsp;Laurent Monassier","doi":"10.1016/j.acvd.2025.03.015","DOIUrl":"10.1016/j.acvd.2025.03.015","url":null,"abstract":"<div><h3>Introduction</h3><div>Pulmonary hypertension is characterized by increased pulmonary vascular resistances leading to right ventricular failure. Chronic hypoxia is a risk factor for PH. End-stage renal disease patients with chronic haemodialysis have increased risk of PH. Most of these are treated with erythropoietin (EPO) because of anaemia. Involvement EPO as causative of PH in controversial.</div></div><div><h3>Objective</h3><div>We investigated if an EPO treatment could reproduce hemodynamic and morphologic features of hypoxia-induced PH and whether endothelial progenitor cells mobilized in PH due to hypoxia, could be involved in EPO-induced PH.</div></div><div><h3>Method</h3><div>The first group of mice was treated with EPO for 2 and 4 weeks and the 2nd group of hypoxia (10%) was exposed during 2 and 4 weeks. Blood analysis, heart and valves remodeling and function were assessed by high frequency echocardiography (Vevo3100 from Visual sonics) using a linear MS440 and MS500 probe. Isovolumetric relaxation and contraction time were recorded with a pulsed-Doppler window placed at the tip of the leaflets valves and right ventricle strain was also evaluated. Blood pressure and heart rate were recorded. Right ventricular pressure, heart and lung histology and blood circulating endothelial progenitor cells were assessed after 2 weeks.</div></div><div><h3>Results</h3><div>The EPO treatment for 2 weeks and 4 weeks and hypoxia induce PH with an important increase in pulmonary and right ventricular pressure and RV/LV<!--> <!-->+<!--> <!-->septum size attested by pulmonary and peripheral vein pressure increases compared to normoxia animals. Similarly, the treatment with EPO or hypoxia in mice significantly alters the inferior vena cava (IVC) pulsatility index with a decrease in inspiratory fractional shortening. EPO and hypoxia groups show right ventricle hypertrophy as attested by an increased in RV/LV<!--> <!-->+<!--> <!-->septum weight ratio and pulmonary artery remodeling increased pulmonary wall vessel thickening of vessels with a diameter below 3–4<!--> <!-->μm (pre-acinar and intra-acinar pulmonary vessels) with an elastic fibrosis of alveolar vessels wall. EPO provoked an increase in the blood mobilization of endothelial progenitor cells at a similar extent than hypoxia.</div></div><div><h3>Conclusion</h3><div>EPO recapitulates hemodynamic features of hypoxia-induced pulmonary hypertension in mice when hematocrit is increased over the physiological range. Nevertheless a pharmacological effect not linked to hematopoiesis is discussed.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Page S178"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099089","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":"Role of Miro1, the mitochondrial Rho GTPase, in cardiomyocyte function and heart homeostasis","authors":"Jean-Sébastien Vartanian-Grimaldi ,&nbsp;Zhenlin Li ,&nbsp;Gaëlle Revet ,&nbsp;Simon Alexandre ,&nbsp;Nathalie Mougenot ,&nbsp;Onnik Agbulut ,&nbsp;Rodriguez Anne-Marie","doi":"10.1016/j.acvd.2025.03.075","DOIUrl":"10.1016/j.acvd.2025.03.075","url":null,"abstract":"<div><h3>Introduction</h3><div>Mitochondria, which are mainly abundant in cardiomyocytes and whose dysfunction has been widely observed in cardiovascular disease, are increasingly being considered as potential therapeutic targets. The function of mitochondria is closely linked to their ability to move along microtubules to adapt their distribution, morphology and dynamics in response to the demands of the cell. The outer mitochondrial membrane protein Miro1 is a key regulator of mitochondrial motility by promoting the anchorage of mitochondria to the kinesin/dynein motor of the microtubules on which they move. The role of Miro1 in cardiomyocytes remains largely unknown.</div></div><div><h3>Objective</h3><div>In this study, we explored the role of Miro1 in the heart using cardiomyocyte-specific deletion of Miro1 in adult mice.</div></div><div><h3>Method</h3><div>We disrupted Miro1 in the adult heart using a heart-specific tamoxifen-inducible Cre recombinase. Two and five weeks after tamoxifen injection, mice were characterized via echocardiography, comprehensive morphological evaluation, metabolic analysis, and transcriptomic profiling.</div></div><div><h3>Results</h3><div>The disruption of Miro1 led to impaired left ventricular function with reduced contractility, subsequently progressing to dilated cardiomyopathy, as demonstrated by serial echocardiography, including tissue Doppler imaging. The cytoarchitecture of cardiomyocytes was altered and display altered mitochondrial architecture. Interestingly, these alterations were associated with an increased fibrosis (assessed by Sirius red staining). These functional and structural defects were preceded by early alterations in the cardiac gene expression program: major decreases in mRNA levels for cardiac α-actin, muscle creatine kinase, and calcium-handling genes and increases in mRNA levels for stress-induced genes such as beta-myosin heavy chain genes, atrial natriuretic factor and brain natriuretic peptide.</div></div><div><h3>Conclusion</h3><div>These results highlight the importance of Miro1 in the maintenance of heart homeostasis and function.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Page S208"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099219","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":"Predictive factors of low cardiac output in patients hospitalized for intermediate-high-risk pulmonary embolism","authors":"Guillaume Faivre-Dupaigre","doi":"10.1016/j.acvd.2025.03.065","DOIUrl":"10.1016/j.acvd.2025.03.065","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;The prognosis of patients hospitalized for intermediate-high-risk pulmonary embolism (PE) varies, with an estimated mortality from 3 to 15%. New therapeutic strategies, such as half-dose fibrinolysis or percutaneous reperfusion techniques, are currently under evaluation in this patient group. The role of these therapeutic strategies remains to be defined.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;To identify clinical and paraclinical factors associated with low cardiac output in patients hospitalized for intermediate-high-risk PE.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Method&lt;/h3&gt;&lt;div&gt;This prospective observational study included patients hospitalized in cardiac intensive care unit for intermediate-high-risk PE at Lille University Hospital between April 2022 and April 2024. After measuring cardiac index (CI) by right heart catheterization, demographic, clinical, biological, and imaging data were described and compared between patients with CI&lt;!--&gt; &lt;!--&gt;≤&lt;!--&gt; &lt;!--&gt;2.5&lt;!--&gt; &lt;!--&gt;L/min/m&lt;sup&gt;2&lt;/sup&gt; and those with CI&lt;!--&gt; &lt;!--&gt;&gt;&lt;!--&gt; &lt;!--&gt;2.5&lt;!--&gt; &lt;!--&gt;L/min/m&lt;sup&gt;2&lt;/sup&gt;. Multivariate logistic regression analysis was performed to identify independent factors associated with low cardiac output.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Among the 82 patients included, 53.7% had a CI&lt;!--&gt; &lt;!--&gt;≤&lt;!--&gt; &lt;!--&gt;2.5&lt;!--&gt; &lt;!--&gt;L/min/m&lt;sup&gt;2&lt;/sup&gt;. This group had biological signs of poor tolerance, including lower prothrombin time (77 vs. 84%, &lt;em&gt;P&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;0.014), lower glomerular filtration rate (71 vs. 88&lt;!--&gt; &lt;!--&gt;L/min/m&lt;sup&gt;2&lt;/sup&gt;, &lt;em&gt;P&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;0.003), and lower mixed venous oxygen saturation (57.4 vs. 68.6%, &lt;em&gt;P&lt;/em&gt; &lt;!--&gt;&lt;&lt;!--&gt; &lt;!--&gt;0.001). Patients with low cardiac output had more dilated right ventricles (RV diameter: 36 vs. 33&lt;!--&gt; &lt;!--&gt;mm, &lt;em&gt;P&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;0.005), reduced RV contractility (TAPSE: 15 vs. 19&lt;!--&gt; &lt;!--&gt;mm, &lt;em&gt;P&lt;/em&gt; &lt;!--&gt;&lt;&lt;!--&gt; &lt;!--&gt;0.001; S’tdi wave: 8 vs. 11&lt;!--&gt; &lt;!--&gt;cm/s, &lt;em&gt;P&lt;/em&gt; &lt;!--&gt;&lt;&lt;!--&gt; &lt;!--&gt;0.001), higher estimated right atrial pressure on echocardiography (&lt;em&gt;P&lt;/em&gt; &lt;!--&gt;&lt;&lt;!--&gt; &lt;!--&gt;0.001), and higher NT-proBNP levels (4366 vs. 2036&lt;!--&gt; &lt;!--&gt;μg/mL, &lt;em&gt;P&lt;/em&gt; &lt;!--&gt;=&lt;!--&gt; &lt;!--&gt;0.001). The two independent predictive factors for low cardiac output were the S’tdi wave measurement and the echocardiographic estimation of right atrial pressure. Clinical parameters did not differ between the two groups. Non-invasive cardiac output measurement via transthoracic echocardiography (TTE) showed good correlation with invasive measurements and acceptable accuracy (mean error of&lt;!--&gt; &lt;!--&gt;±&lt;!--&gt; &lt;!--&gt;0.40&lt;!--&gt; &lt;!--&gt;L/min/m&lt;sup&gt;2&lt;/sup&gt;).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Half of the patients admitted for intermediate-high-risk PE have impaired cardiac output. Identifying these patients based only on clinical parameters is challenging. TTE appears to be the most effective tool for identifying the most severe cases, enabling the consideration of interventional or pharm","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Page S203"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099204","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":"Cardiac tamponade: Clinical, etiological and therapeutic features","authors":"Syrine Saidane ,&nbsp;Sana Said ,&nbsp;Younes El Kharras ,&nbsp;Walid Ben Fakih ,&nbsp;Khadija Mzoughi ,&nbsp;Ihsen Zairi ,&nbsp;Sondos Kraiem","doi":"10.1016/j.acvd.2025.03.037","DOIUrl":"10.1016/j.acvd.2025.03.037","url":null,"abstract":"<div><h3>Introduction</h3><div>Cardiac tamponade is a life-threatening diagnostic and therapeutic emergency.</div></div><div><h3>Objective</h3><div>The aim of our study was to investigate the clinical, etiological and therapeutic characteristics of patients hospitalized for tamponade.</div></div><div><h3>Method</h3><div>This was a retrospective monocentric study including 40 patients admitted for tamponade to our cardiology department between January 2018 and June 2023.</div></div><div><h3>Results</h3><div>The mean age was of 60<!--> <!-->±<!--> <!-->16 years [17,84] with a sex ratio of 2.3. The mode of onset of symptomatology was progressive in 80% of the cases. Dyspnea was constant. The main findings on physical examination were: muffled heart sounds (98%), polypnea (100%), and tachycardia (78%). Mean arterial pressure was 80 mmHg<!--> <!-->±<!--> <!-->15 [47,110]. Paradoxical pulse was present in 15% of cases (<em>n</em> <!-->=<!--> <!-->6). Arterial hypotension was present in 28% (<em>n</em> <!-->=<!--> <!-->11). Signs of right heart failure were present in 11 patients (28%). The main electrical abnormalities reported were: microvoltation (83%), atrial fibrillation (18%) and electrical alternation (30%). Transthoracic echocardiography revealed circumferential effusion in all patients. A “swinging heart” appearance was found in 30% of the cases (<em>n</em> <!-->=<!--> <!-->12). All patients had signs of hemodynamic compression. Thirty-six patients (90%) were drained percutaneously. Surgical drainage was performed immediately in 4 patients and secondarily in only 1 patient whose pericardial puncture was complicated by a right ventricle wound. Neoplastic origin was the main etiology and was found in 14 patients (35%). All cases were secondary neoplasia, and the primary tumor was mainly bronchopulmonary cancer (10 cases) (<span><span>Figure 1</span></span>). Viral origin was the second most common etiology, found in 25% of cases. Other etiologies were iatrogenic (20%), idiopathic (7%), uremic (5%), tuberculosis (5%) and bacterial (3%). The average hospital stay was 8<!--> <!-->±<!--> <!-->5 days [3,27]. The 30-day mortality rate was 12%. Two patients (5%) had a recurrent event: the first case was a neoplasic tamponade and the second was a viral tamponade. No cases of transition to constriction were reported.</div></div><div><h3>Conclusion</h3><div>Tamponade is a serious pathology requiring urgent and effective management. Prognosis depends on the quality of therapeutic management and the nature of the causative pathology.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Page S189"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099558","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":"ADP-ribosylation in a mouse model of atherosclerosis: A potential novel link between dyslipidemia and inflammation in cardiovascular disease","authors":"Constance Delwarde,&nbsp;Diego Pestana,&nbsp;Taku Kasai,&nbsp;Shio Kuraoka,&nbsp;Yuto Nakamura,&nbsp;Takeshi Okada,&nbsp;Julius Decano,&nbsp;Ge Rile,&nbsp;Andrew Mlynarchik,&nbsp;Katelyn Perez,&nbsp;Alesandra Campedelli,&nbsp;Sarvesh Chelvanambi,&nbsp;Sasha Singh,&nbsp;Elena Aikawa,&nbsp;Masanori Aikawa","doi":"10.1016/j.acvd.2025.03.004","DOIUrl":"10.1016/j.acvd.2025.03.004","url":null,"abstract":"<div><h3>Introduction</h3><div>Inflammation and lipid accumulation are major features of atherosclerosis, a leading cause of death and morbidity worldwide. Our previous study recognized ADP-ribosylation, a post-translational modification, as a novel regulator of macrophage activation. We also have established mass spectrometry-based ADP-ribosylation proteomics. Using this technology, we evaluated the completely uncharacterized role of ADP-ribosylation in atherogenesis.</div><div>Objectif We hypothesized that ADP-ribosylated proteins circulate from liver, accumulate in aorta and promote atherogenesis.</div></div><div><h3>Method</h3><div>We harvested the aorta, liver, and plasma of LDL receptor-deficient (Ldlr-/-) mice that were on a regular chow or high-fat diet for 3 or 6 months (<em>n</em> <!-->=<!--> <!-->40/condition).</div></div><div><h3>Results</h3><div>To increase ADP-ribosyl peptide signals in the aorta, we applied our novel recently optimized ion mobility mass spectrometry strategy to generate ADP-ribosylation proteomics data. We analyzed 160 mice aortas and identified 3 APOA1 and 3 APOE ADP-ribosylated peptides in both the aorta and the liver (<span><span>Fig. 1</span></span> A). In addition, these peptides were differentially abundant in the aorta of HFD-fed mice, compared to controls (i.e, APOA1 ARPALEDLR peptide relative abundance [<span><span>Fig. 1</span></span> B]). Using the same mouse plasma, we then validated the presence of ADP-ribosylated APOA1 and ADP-ribosylated APOE in HDL and chylomicron/VLDL/LDL fractions (Western blot), respectively. This finding indicates that classical apolipoproteins circulate as ADP-ribosylated forms, representing a completely novel class of modified apolipoproteins. Immunohistochemistry confirmed the enrichment of aortic lesions in macrophages and ADP-ribosylation signal (5-fold increase, <em>P</em> <!-->=<!--> <!-->0.0006).</div></div><div><h3>Conclusion</h3><div>This work provides the first in vivo evidence that ADP-ribosylation occurs in atherosclerotic lesions, which may originate from the liver via circulating blood (<span><span>Fig. 1</span></span>C). Future studies will examine whether ADP-ribosylation of apolipoproteins, specifically APOA1, alters anti-atherogenic functions of HDL.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Page S172"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099589","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":"Cardiovascular risk factors have an impact on the biology of pericytes","authors":"Célia Bourguignon,&nbsp;Virginie Grouthier,&nbsp;Candice Chapouly,&nbsp;Thierry Couffinhal,&nbsp;Marie-Ange Renault","doi":"10.1016/j.acvd.2025.03.020","DOIUrl":"10.1016/j.acvd.2025.03.020","url":null,"abstract":"<div><h3>Introduction</h3><div>Pericytes are critical for capillary health and function; however, whether and how they may contribute to the pathophysiology of cardiovascular diseases is poorly known. Notably, while the detrimental effects of cardiovascular risk factors on endothelial cells have been extensively studied, little is known about their impact on the biology of pericytes.</div></div><div><h3>Objective</h3><div>Our aim was to investigate pericyte homeostasis in the heart and brain of adult mice, after they have been exposed to type 2 diabetes or depleted by 50%.</div></div><div><h3>Method</h3><div>In vivo, to deplete pericytes, we used Pdgfrb-Cre/ERT2; Rosa-DTA mice in which diphtheria toxin expression is specifically induced in mural cells after tamoxifen injections. Type 2 diabetes was induced in C57BL6/J mice by a high fat diet (HFD; 60% of fat) regimen combined with low dose-streptozotocin (STZ) injections. In vitro experiments were performed on primary cultured mouse cardiac pericytes isolated from 7–14 days-old pups.</div></div><div><h3>Results</h3><div>In diabetes, cardiac pericyte density is reduced by 20% in C57BL6/J mice, suggesting compromised pericyte survival or renewal/proliferation is compromised by diabetes. To investigate whether hyperlipidemia and/or hyperglycemia affect these processes, we conducted in vitro and in vivo assays using cultured cardiac pericytes and DTA mice. We first characterized pericyte renewal in normal conditions by depleting 50% of pericytes in mice. Pericyte regeneration in the heart starts on day 4 after depletion and is almost complete by day 21 (pericyte density<!--> <!-->=<!--> <!-->91% of controls). Consistently, cell proliferation, measured by KI67 staining, was observed from day 4 to day 14 post-depletion. Interestingly, pericyte renewal kinetic seems to be organ-specific: brain pericyte regeneration is slower (71% of controls after 28 days). To test the effects of hyperlipidemia and hyperglycemia on proliferation, mice were fed a high-fat diet or treated with STZ before pericyte depletion. Neither condition impaired pericyte proliferation. In vitro, glucose, free fatty acids, or LDL did not affect BrdU incorporation in cultured pericytes. However, hyperlipidemia may reduce pericyte survival, as free fatty acids, notably palmitate and oleate, significantly increased necrosis in vitro.</div></div><div><h3>Conclusion</h3><div>This study indicates that pericytes can undergo extensive remodeling after a stress in adults. Cardiovascular risk factors, such as obesity and diabetes, may impair pericyte survival in the heart suggesting that these cells, known to be critical for microvascular integrity, could contribute to the onset of cardiac diseases.</div></div>","PeriodicalId":55472,"journal":{"name":"Archives of Cardiovascular Diseases","volume":"118 6","pages":"Page S180"},"PeriodicalIF":2.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099094","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}