Program
08:00 am – 08:30 am – Welcome Coffee
08:30 am – 08:45 am – Opening speeches
- Pr Stéphane HATEM, General Director
- Anne-Marie ARMANTERAS, President of the Board.
08:45 am – 09:30 am – Opening Keynote
Moderator: Stéphane HATEM
Cardio-Immunology: At the Heart of Immunity
Jean-Sébastien SILVESTRE
Director, Paris Cardiovascular Research Center (PARCC)
09:30 am – 11:00 am – Session 1: Research in Metabolic Diseases
Moderators: Jérémie GAUTHERON, Chloé AMOUYAL
- Combining machine learning and metabolomics to identify the metabolic signatures of polycystic ovary syndrome patients according to body mass index.
Tatiana LECOT-CONAN
Department: Endocrinology and Reproductive Medicine, Pitié-Salpêtrière Hospital, APHP.
- Unravelling the Impact of adipose-glucocorticoid signaling on age-related metabolic disorders
Carine BEAUPÈRE
Team: Lipodystrophies, Metabolic and Hormonal Adaptations, and Aging
UMRS_938, Saint-Antoine Research Center (CRSA)
- Adipocyte-specific Mlkl knockout mitigates obesity-induced metabolic dysfunction by enhancing mitochondrial functions
Juliette TOKGOZOGLU
Team: Metabolic and Biliary Fibro-inflammatory Liver Diseases
UMRS_938, Saint-Antoine Research Center (CRSA)
- Contribution of adipocyte ABCG1 expression to obesity and associated metabolic disorders.
Canelle REYDELLET
Team: Cellular and Systemic Lipid Metabolism in Cardiometabolic Diseases
UMRS_1166-ICAN, Cardiovascular and Metabolic Diseases
- Effects of GLP-1 receptor agonists on insulin resistance, dyslipidemia, and hepatic steatosis in patients with familial partial lipodystrophy
Camille VATIER
Team: Lipodystrophies, Metabolic & Hormonal Adaptations, and Aging
UMRS_938, Saint-Antoine Research Center (CRSA)
Department: Endocrinology, Diabetology, and Reproductive Endocrinology, Saint-Antoine Hospital, APHP
- Liver heart crosstalk: the role of hepatic S1P in metabolic heart disease development
Franck PHAN
Team: Metabolic Diseases, Diabetes, and Comorbidities
UMRS_1166-ICAN, Cardiovascular and Metabolic Diseases
Department: Diabetology, Pitié-Salpêtrière Hospital, APHP
11:00 am – 11:15 am – Coffee Break
11:15 am – 12:45 am – Session 2: Clinical Cardiovascular Research
Moderators : Nadjia KACHENOURA, Estelle GANDJBAKHCH
- Phenotyping heterogeneity of recurrent myocarditis in the AMPHIBIA registry
Mathieu PROUST
Department: Cardiology, PSL
- Nailfold Capillaroscopic Findings in Patients with Suspected Microvascular Angina
Niki PROCOPI
Team: Atherothrombosis and Applied Pharmacology
UMRS_1166-ICAN, Cardiovascular and Metabolic Diseases
Department: Cardiology, Pitié-Salpêtrière Hospital
- Computational Fluid Dynamics Analysis of Left Atrial Blood Flow in Patients with Atrial Fibrillation
Louis PARKER
Team: Cardiovascular Imaging – LIB Biomedical Imaging Laboratory Inserm U1146 CNRS UMR 7371
- AI-Driven Multimodal Insights in Atrial Cardiomyopathy
Maharajah PONNAIAH
Platform: ICAN I/O – Data Science
- Updates on Boehringer Ingelheim pipeline
Delphine BOUSQUET
National Lead for Scientific Experts
Boehringer Ingelheim – Sponsor
12:45 pm – 02:00 pm – Lunch Break
02:00 pm – 03:30 pm – Poster Session
Jury: Michel ZEITOUNI, Maryse GUÉRIN, Bruno FÈVE
03:30 pm – 04:30 pm – Session 3: Fundamental & Translational Cardiovascular Research
Moderators: Laurent KAPPELER, Marie LAGOUGE
- Clinical development in cardiometabolism
Dr Isabelle Lonjon-Domanec
VP CMR, Novo Nordisk France- Sponsor
- Targeted mRNA sequencing and refined bioinformatics pipeline as an innovative way to reclassify splicing variants in Hypertrophic Cardiomyopathies and improve diagnostic yield
Laetitia Rialland
Team: Genomics and Pathophysiology of Cardiovascular Diseases
UMRS_1166-ICAN, Cardiovascular and Metabolic Diseases
- Distinct role of macrophages in atrial cardiomyopathy associated to obesity
Nadine SUFFEE
Team: Molecular and Cellular Plasticity in Cardiovascular Diseases
UMRS_1166-ICAN, Cardiovascular and Metabolic Diseases
- Cardiometabolic trajectories in familial hypercholesterolemia
Antonio GALLO
Unit of Lipidology and Cardiovascular Prevention, Competence Center for Rare Dyslipidemias (CEDRA),
Department of Nutrition, Pitié-Salpêtrière Hospital, APHP
04:30 pm – 05:15 pm – Closing Keynote
Moderator: Fabienne FOUFELLE
Microvascular Endothelial Cells in Adipose Tissue: Exploring their heterogeneity and functional diversity
Anne BOULOULMIÉ
Institute of Metabolic and Cardiovascular Diseases
Inserm UMR 1297 – University of Toulouse
05:15 pm – 05:30 pm – Award Ceremony
Bruno FÈVE, Wilfried LE GOFF
Organizing Committee
Marie LAGOUGE, Véronique BEREZIAT, Wilfried LE GOFF
Oral presentation judges
Michel ZEITOUNI, Maryse GUÉRIN, Bruno FÈVE
Poster judges
05:30 pm – 05:45 pm : Concluding remarks
Pr Stéphane HATEM, General Director
Opening Keynote – Cardio-Immunology: At the Heart of Immunity
Moderator: Pr Stéphane Hatem
Director, Paris Cardiovascular Research Center – PARCC Université Paris Cité
Biography
Jean-Sébastien Silvestre is a researcher in cardiovascular pathophysiology. He earned his PhD from Paris Diderot University in 1998, followed by postdoctoral training at the University of California, Los Angeles (UCLA). After serving as Associate Professor at Paris Diderot University and Junior Member of the Institut Universitaire de France, he joined INSERM in 2008 as Research Director at the Paris Cardiovascular Research Center (PARCC), where he currently serves as Director. His research focuses on the molecular and cellular mechanisms associated with cardiac ischemia, particularly immuno-inflammatory interactions involved in ischemic cardiovascular diseases. He has authored over 160 scientific publications and contributed to around twenty reference works.
Summary – Cardio-Immunology: At the Heart of Immunity
Numerous biological mechanisms converge to remodel the heart following a myocardial infarction (MI). Unfavorable post-ischemic cardiac remodeling and progression towards heart failure can be promoted by macroscopic alterations in the geometry and function of the left ventricle, as well as microscopic changes in the cellular and molecular components of the ischemic heart. Extensive experimental and clinical evidence implicates cells of the innate and adaptive immune systems in post-MI remodeling. A detailed understanding of the interactions between inflammation and cardiac pathology is a major challenge in cardiovascular research and could lead to the development of immunotherapy strategies for the treatment of ischemic cardiovascular diseases.
Our research has focused specifically on the roles of lymphocytes and macrophages in this context. Regarding lymphocytes, we demonstrated that mature B lymphocytes, particularly follicular B cells and marginal zone B cells, have distinct functions and influence the recovery of cardiac function following MI. Additionally, our work highlights the detrimental impact of cytotoxic lymphocytes post-MI, opening avenues for targeted therapeutic strategies.
Concerning macrophages, we investigated the complex dialogue between these cells and cardiomyocytes. We will present recent findings on how this cardiomyocyte-macrophage interaction modulates harmful or reparative signaling pathways within damaged cardiac tissue.
Session 1 – Research in Metabolic Diseases
Moderators: Jérémie GAUTHERON et Chloé AMOUYAL
1 – Combining machine learning and metabolomics to identify the metabolic signatures of polycystic ovary syndrome patients according to body mass index
Tatiana LECOT-CONAN
Department: Endocrinology and Reproductive Medicine, Pitié-Salpêtrière Hospital, APHP.
Introduction: Polycystic ovary syndrome (PCOS) is frequently associated with metabolic disorders such as obesity and/or insulin resistance. A metabolic assessment is recommended by 2023 ESHRE PCOS guidelines in all patients, regardless of body mass index (BMI). However, in the literature, normal-weight PCOS patients are less explored and the increased risk of diabetes in this population is still in debates. The aim of this study was to identify the associated metabolic profile of normal-weight patients with PCOS.
Material and methods: A retrospective study in the Pitié-Salpêtrière endocrinology department was conducted between January 2019 and December 2023. Clinical and biological data were collected during day hospital check-up. PCOS patients were classified into 3 BMI categories: 152 patients with a normal BMI (< 25 kg/m²), 96 overweight patients (25-30 kg/m²) and 149 obese patients (BMI ≥ 30 kg/m²). All 76 control patients had a normal BMI. To identify metabolomic profile according to BMI, we used a combined mass spectrometry and machine learning approach. In addition to bio clinical parameters, we have also integrated blood steroidome (including 20 molecular species quantify thanks to mass spectrometry).
Results: HOMA-IR, to assess insulin resistance, was higher in the obese group than in the overweight and normal BMI groups (p<0.0001) and HOMA-IR> 2.5 was more frequent in obese PCOS patients. Lean PCOS patients presented a better metabolic profile with high HDLc, low LDLc and triglycerides, and normal liver function. In terms of hormonal assessment, due to a higher SHBG, lean patients have a lower bioavailable testosterone than obese PCOS patients (p < 0.0001). The LC-MS/MS circulating steroid profiles showed increase in delta5 steroids in normal-weight PCOS patients compared to obese PCOS women but there was no difference with control cohort. To identify a characteristic metabolomic signature, we used a combined approach including mass spectrometry data and machine learning modeling. We used this approach to characterize PCOS patients compared to control patients and to characterize PCOS patients according to their BMI. The resulting model showed a continuum between hormonal variables on the one hand and metabolic variables on the other hand. Interestingly, some obese patients were metabolically healthy and positioned on the hormonal side. In contrast, some lean patients had a more metabolic profile.
Conclusion: Metabolic profile of normal-weight PCOS patients is characterized by lower HOMA-IR, higher HDLc and bioavailable testosterone, and normal lipid and liver functions.
2 – Unravelling the Impact of adipose-glucocorticoid on age-related metabolic disorders on age-related metabolic disorders
Carine BEAUPÈRE
Team: Lipodystrophies, Metabolic and Hormonal Adaptations, and Aging
UMRS_938, Saint-Antoine Research Center (CRSA)
A. Murali1,2, H. Soula2,3 M. Nouvel2,4, C. Vigouroux1, 2, 4, A. Groslfeld1,2*, M. Moldes1,2*, B. Fève1, 2, 4*, C. Beaupère1,2
1 Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, F-75012 Paris, France
2 Fondation pour l’Innovation en Cardiométabolisme et Nutrition (ICAN), Sorbonne Université, 75013, Paris, France.
3 Sorbonne Université, INSERM, Nutrition and Obesity : Systemic Approaches, Paris, France.
4 Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Hôpital Saint-Antoine, Service Endocrinologie, CRMR PRISIS, 75012 Paris, France
Summary:
Hypercortisolism increases the risk of cardio-metabolic diseases associated with aging. At the same time, cortisol secretion changes with age. The use of synthetic glucocorticoids (GCs) has highlighted their significant impact on insulin-sensitive tissues. We previously demonstrated the central role of adipose tissue (AT) in the development of GC-induced cardio-metabolic disorders, particularly through a murine model with adipocyte-specific glucocorticoid receptor (GR) deletion (adipoGR-KO). Young adult adipoGR-KO mice are protected from the harmful effects of GCs, exhibit healthier fat expansion, and show improved insulin sensitivity.
However, the influence of aging on GC signaling—and conversely, the effects of GCs on aging and cellular senescence, particularly in AT—remains unclear.
Using the AdipoGR-KO model developed in our lab, we compared the metabolic adaptations of young (18 weeks) and aged (14 months) mice in response to corticosterone, the primary endogenous GC in rodents. We then explored the pro-senescent effects of GCs in AT, both in vivo and in vitro using human adipose stem cells. Additionally, we examined the role of GR in the observed senescence process.
Several findings suggest that GR plays a key role in regulating cellular senescence:
i) GC signaling activation correlates with the expression of p21CIP1, a senescence marker, both in vitro and in vivo
ii) adipocyte-specific GR deletion improves insulin sensitivity in aged mice
iii) aging and cellular senescence alter GC sensitivity
iiii) modulating GC signalling can partially reverse replicative or premature senescence.
Overall, these results suggest that GCs contribute to metabolic aging and cellular senescence. More importantly, targeting GR signalling could be a promising therapeutic strategy to prevent metabolic aging and treat premature aging syndromes.
3 – Adipocyte-specific Mlkl knockout mitigates obesity-induced metabolic dysfunction by enhancing mitochondrial functions
Juliette TOKGOZOGLU
Team: Metabolic and Biliary Fibro-inflammatory Liver Diseases
UMRS_938, Saint-Antoine Research Center (CRSA)
Juliette Tokgozoglu1,2*, Valeria Pistorio1,2,3*, Mirko Minini1,2,Pierre-Antoine Soret1,2, Virginie Steunou1,2, Jean-Louis Delaunay1,2, Julien Castel4, Serge Luquet4, Ivan Nemazanyy5, Carine Beaupère1,2, Aurore Lhonore6, Tatiana Ledent1, Sara Lemoinne1,2, Chantal Housset1,2,Philippe Lesnik2,3, Vlad Ratziu2,7, Bruno Fève1,2,8, Tounsia Aït-Slimane1,2, Axelle Cadoret1,2, Nicolas Chignard1,2, Jérémie Gautheron1,2#
1 Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, F-75012 Paris, France.
2 Fondation pour l’Innovation en Cardiométabolisme et Nutrition, IUH-ICAN, F-75013 Paris.
3 Sorbonne Université, INSERM, UMR_S1166, F-75013 Paris.
4 Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, Paris, F-75013
5 Université Paris Cité, Structure Fédérative de Recherche Necker, Platform for Metabolic Analyses, F-75015 Paris.
6 Sorbonne Université, INSERM, Institut de Biologie Paris Seine, IBPS, F-75005 Paris.
7 Sorbonne Université, INSERM, Centre de Recherche des Cordeliers, F-75006 Paris.
8 Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, Service Endocrinologie, F-75012 Paris.
Aims/hypothesis: Obesity is a global epidemic characterized by chronic low-grade inflammation and metabolic dysfunction, with adipose tissue serving as a pivotal regulator of whole-body energy balance. In addition to its canonical role in necroptosis, the mixed lineage kinase domain-like pseudokinase (MLKL) may exert non-canonical functions in metabolic regulation. We hypothesized that adipocyte-specific Mlkl deficiency would attenuate high-fat diet (HFD)-induced obesity and improve systemic metabolic parameters, including glucose tolerance, insulin sensitivity, and liver steatosis.
Methods: We generated and characterized MlklAdi-KO mice, in which MLKL is selectively deleted in mature adipocytes. Mice were fed either a normal chow diet or a HFD. We assessed body weight, glucose tolerance, insulin sensitivity, energy expenditure, and adipose and liver phenotypes. White adipose tissue (WAT) was subjected to transcriptomic and metabolomic analyses to identify pathways altered by Mlkl deficiency. We also examined adipocyte differentiation in vitro using 3T3-L1 cells genetically ablated for Mlkl.
Results: Adipocyte-specific Mlkl deficiency reduced susceptibility to HFD-induced obesity, enhanced glucose tolerance, and improved insulin sensitivity. MlklAdi-KO mice exhibited increased energy expenditure, which was independent of changes in food intake or locomotor activity, suggesting that MLKL influences adipose tissue function and systemic metabolism through distinct mechanisms under HFD. Transcriptomic analyses of visceral white adipose tissue (visWAT) showed significant modulation of pathways related to oxidative phosphorylation, inflammation, and lipid metabolism. Metabolomic profiling further revealed decreases in tricarboxylic acid (TCA) cycle intermediates, acylcarnitines, and pro-inflammatory amino acids in HFD-fed MlklAdi-KO mice. These improvements were accompanied by reduced hepatic lipid accumulation and steatosis. Mechanistically, Mlkl deficiency also influenced adipocyte differentiation potential, as partially restored by MLKL re-expression in vitro.
Conclusions: Our findings demonstrate that adipocyte-specific Mlkl deficiency alleviates HFD-induced metabolic dysfunction by enhancing mitochondrial function, reducing lipid accumulation in adipose tissue, and mitigating hepatic steatosis. These data underscore the critical role of MLKL in adipose tissue homeostasis and position MLKL as a potential therapeutic target for obesity and associated metabolic disorders. Future studies involving conditional knockout and overexpression models will be necessary to delineate MLKL’s cell-specific and non-canonical pathways in metabolic regulation.
4 – Contribution of adipocyte ABCG1 expression to obesity and associated metabolic disorders.
Canelle REYDELLET
Team: Cellular and Systemic Lipid Metabolism in Cardiometabolic Diseases
UMRS_1166-ICAN, Cardiovascular and Metabolic Diseases
Canelle Reydellet, Veronica D. Dahik, Clément Materne, Éric Frisdal, Éric Bun, Marie Lhomme, Maharajah Ponnaiah, Lise M. Hardy, Lucie Poupel, Hervé Durand, Isabelle Guillas, Maryse Guérin, Wilfried Le Goff.
Introduction: Obesity is one of the major health challenges of the 21st century and is frequently associated with metabolic disorders such as insulin resistance and type 2 diabetes. Our previous work has shown that the ATP-Binding Cassette G1 (ABCG1) membrane transporter plays a key role in fat mass formation by promoting lipoprotein lipase-dependent triglyceride storage in adipocytes. This function suggests that ABCG1 may contribute to adipocyte hypertrophy in the context of diet-induced obesity, with consequences for the development of obesity-associated metabolic disorders.
Objective: To investigate the impact of adipocyte-specific Abcg1 deficiency on the development of diet-induced obesity.
Results: Mice with adipocyte-specific Abcg1 deficiency (Abcg1^ADIPOKO, Abcg1^flox/flox x Adipoq-CreERT2) were fed a high-fat diet (60% kcal) for 30 weeks. While Abcg1 deletion in adipocytes does not appear to affect insulin resistance parameters in the early stages of obesity, glucose tolerance is improved at later stages of the disease. In adipocytes, Abcg1 deletion leads to major remodeling of lipid homeostasis and increased insulin-independent glucose uptake. Furthermore, Abcg1 deletion reduces adipocyte hypertrophy, resulting in the restoration of adipocyte function. Similarly, induction of Abcg1 deficiency in adipocytes of obese mice improves glucose tolerance and overall plasticity of gonadal adipose tissue.
Conclusion: Overall, our study highlights the critical role of the ABCG1 transporter in adipocytes in adipose tissue remodeling and glucose homeostasis during diet-induced obesity.
5 – Effects of GLP-1 receptor agonists on insulin resistance, dyslipidemia, and hepatic steatosis in patients with familial partial lipodystrophy
Camille VATIER
Team: Lipodystrophies, Metabolic & Hormonal Adaptations, and Aging
UMRS_938, Saint-Antoine Research Center (CRSA)
Department: Endocrinology, Diabetology, and Reproductive Endocrinology, Saint-Antoine Hospital, APHP
Sophie Lamothe, Ines Belalem, Marie Christine Vantyghem, Estelle Nobecourt, Héléna Mosbah, Hippolyte Dupuis, Paul Vandenbroere, Stéphanie Jelliman, Chloé Amouyal , Samy Hadjadj, Corinne Vigouroux, Camille Vatier
Introduction: Familial partial lipodystrophies (FPLD) are rare genetic disorders characterized by partial loss of adipose tissue and metabolic disturbances associated with insulin resistance. While GLP-1 receptor agonists (GLP-1 RAs) have proven effective in type 2 diabetes, little data is available in lipodystrophic patients. Through the PRISIS network, we evaluated the real-world efficacy and tolerance of GLP-1 RAs in these patients.
Patients and Methods: A total of 76 patients with familial partial lipodystrophy (FPLD) who received GLP-1 RA treatment as part of their clinical follow-up were included. The majority of patients (74%) had FPLD type 2. 87% were women, with a mean age at diabetes diagnosis of 27 years.
Results: After an average treatment duration of 4 years with GLP-1 RAs, lipodystrophic patients showed significant metabolic improvement: HbA1c decreased from 8.2% to 7.3% (p < 0.0001), Body Mass Index from 26 kg/m² to 24.9 kg/m² (p < 0.001), LDL cholesterol from 0.85 g/L to 0.73 g/L (p = 0.01), triglycerides from 2.9 g/L to 2 g/L (p = 0.05), and GGT from 46 IU/L to 38 IU/L (p = 0.007). Fibroscan analysis showed improvement in liver fibrosis. Nine patients discontinued treatment due to intolerance.
Conclusion: In patients with lipodystrophic syndromes, GLP-1 RA treatment is beneficial in terms of weight loss, glycemic control, dyslipidemia, and hepatic steatosis.
6 – Liver heart crosstalk: the role of hepatic S1P in metabolic heart diseases development
Franck PHAN
Team: Metabolic Diseases, Diabetes, and Comorbidities
UMRS_1166-ICAN, Cardiovascular and Metabolic Diseases
Department: Diabetology, Pitié-Salpêtrière Hospital, APHP
S. Slablab1,2,3, A. Jean1,2,3, O. Bourron1,2,3,4, V. Ratziu1,3,4,5, E. Hajduch1,2,3, S. Hatem1,3,6,7, M. Guérin1,3,8, W Le Goff1,3,8, S. Besse1,2,3, N. Suffee1,3,6, F. Foufelle1,2,3, F. Phan1,2,3,4
1- Sorbonne Université, Paris, France
2- INSERM, UMRS 1166, Equipe « Maladies Métaboliques, Diabète and Co-morbidités », Paris, France
3- Institute of Cardiometabolism and Nutrition ICAN, Paris, France
4- Assistance Publique-Hôpitaux de Paris (APHP), Sce de Diabétologie, Pitié-Salpêtrière, Paris, France
5- Assistance Publique-Hôpitaux de Paris (APHP), Sce d’Hépatologie, Pitié-Salpêtrière, Paris, France
6- INSERM, UMRS 1166, Equipe « Plasticités cellulaire et moléculaire dans les maladies cardiovasculaires », Paris, France
7- Assistance Publique-Hôpitaux de Paris (APHP), Sce de Cardiologie, Pitié-Salpêtrière, Paris, France
8- INSERM, UMRS 1166, Equipe « Métabolisme lipidique cellulaire et systémique dans les maladies cardiométaboliques », Paris, France
Introduction : Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a key contributor to metabolic cardiopathy. Sphingosine-1-phosphate (S1P), a bioactive lipid, plays a crucial role in hepatic and cardiovascular homeostasis. In pathological conditions such as obesity and type 2 diabetes, plasma and hepatic S1P levels are elevated, suggesting a potential contribution of hepatic S1P to cardiac dysfunction. This study investigates the impact of hepatic S1P on cardiac homeostasis using murine models challenged with a high-fat diet (HFD) and genetically modified mice with hepatic SphK1 deletion.
Methods and Materials : C57BL/6 mice were fed an HFD (60% lipids, 21% carbohydrates, 19% proteins) for 16 weeks to assess the impact of lipid overload on S1P expression and cardiac function. Additionally, SphK1-KO liver-specific knockout mice were utilized to determine the hepatic contribution to circulating and cardiac S1P levels. S1P quantification, receptor expression analysis (S1PR1, S1PR2, S1PR3), inflammatory markers, and cardiac fibrosis assessments were performed through molecular analyses. Cardiac function was evaluated via echocardiography and electrocardiography.
Results: HFD-fed mice exhibited increased hepatic and cardiac S1P levels, correlating with upregulated S1PR2/S1PR3 expression and a pro-inflammatory cardiac environment. Conversely, hepatic SphK1-KO mice showed a significant reduction in hepatic (-25%) and cardiac (-50%) S1P levels. This reduction was associated with decreased expression of pro-inflammatory and fibrotic S1P receptors, leading to improved cardiac function. These mice displayed reduced atrial fibrillation duration, less ventricular fibrosis, and preserved ventricular strain compared to HFD-fed controls.
Discussion : These findings suggest that hepatic S1P acts as a mediator in the liver-heart axis, influencing cardiac inflammation and fibrosis in metabolic disease conditions such as hepatic steatosis. Targeting hepatic S1P synthesis may represent a novel therapeutic strategy for preventing metabolic cardiopathy. Further studies are needed to explore pharmacological modulation of S1P signaling in cardiometabolic disorders.
Session 2: Clinical Cardiovascular Research
Moderators: Nadjia KACHENOURA et Estelle GANDJBAKHCH
1 – Phenotyping heterogeneity of recurrent myocarditis in the AMPHIBIA registry
Mathieu PROUST
Department : Cardiology, Pitié-Salpêtrière Hospital
Matthieu Proust, Marc Pineton de Chambrun, Deborah Foltran, Estelle Gandjbakhch, Julie Proukhnitzky, Philippe Charron, Alban Redheuil, Benjamin Bertin, Karim Aacha, Michel Zeitouni, Fleur Cohen, Guillaume Hekimian, Alain Combes, Eric Vicaut, Gilles Montalescot, Johanne Silvain, Mathieu Kerneis, ACTION Study Group
BACKGROUND
Recent evidence supports that there is an overlap between recurrent acute myocarditis and genetic arrhythmogenic cardiomyopathy such as desmosomal or titin-related cardiomyopathy. To date, there are limited data on the phenotyping heterogeneity of recurrent myocarditis. The aim of this analysis using the AMPHIBIA registry is to cluster different phenotypes associated with recurrences and evaluate the association between these phenotypes and the risk of outcomes.
METHODS
This is an observational ambispective cohort study based on the AMPHIBIA cohort (NCT04844151), carried out by Assistance Publique – Hôpitaux de Paris and the ACTION Study Group, including patients with proven myocarditis hospitalized between 2008 and 2024 at the Pitié Salpétrière Hospital. The diagnosis of acute myocarditis is based on the presence of acute symptoms, elevated cardiac troponin and the presence of Lake Louise criteria on CMR imaging or histologically proven. Recurrence is defined as at least 2 distinct episodes of acute myocarditis. Key exclusion criteria include the diagnosis of toxic drug-induced myocarditis or the presence of a any other cardiac or extracardiac cause that may explain the clinical presentation. Outcomes include temporary circulatory support implantation, heart transplantation, death, multiples recurrences, arrhythmias, and conduction disorders.
RESULTS
From August 2008 to December 2023, 609 cases of acute myocarditis were included. 26 patients were excluded (immune checkpoint or chemotherapy-related myocarditis, severe coronary artery disease associated…). Among these patients, we identified 71 patients (12%) with recurrent myocarditis (male 75%; median age 28,7 years). The median follow-up was 3,2 years (1,4 – 8,3 years). The median LVEF on admission on trans-thoracic echography was 60%.
7 patients (9,8%) required temporary external hemodynamic support. Detailed phenotypes include three main presentations: idiopathic (73,2%: viral), autoimmune (12,6%: systemic lupus erythematosus, eosinophilic granulomatosis with polyangiitis…), and genetic recurrent myocarditis (7%: desmosomal genes variants…). The features of interest including clinical, biological, etiological, echocardiographic, CMR imaging, genetic and histological data and the rate of outcomes will be available for the ICAN meeting.
CONCLUSIONS
To our knowledge, this will be the first study defining phenotypes associated with recurrent myocarditis. Identifying these phenotypes is crucial to stratify the risk of recurrences and development of genetic cardiomyopathy. These phenotypes may help physicians in guiding the therapeutic managements of these patients.
2 – Nailfold Capillaroscopic Findings in Patients With Suspected Microvascular Angina
Niki PROCOPI
Team: Atherothrombosis and Applied Pharmacology
UMRS_1166-ICAN, Cardiovascular and Metabolic Diseases
Department: Cardiology, Pitié-Salpêtrière Hospital
Background: Coronary microvascular dysfunction (CMD) is a major condition underlying angina with no obstructive coronary arteries (ANOCA). Whether coronary microvascular dysfunction is part of a systemic microvascular disease remains unclear. Nailfold videocapillaroscopy (NVC) offers a non-invasive window into peripheral microcirculation.
Objective: Our study aims to assess whether CMD is associated with nailfold capillary abnormalities in patients with suspected ANOCA.
Methods: This single-center prospective cohort included patients evaluated for ANOCA using invasive coronary microcirculation testing by continuous thermodilution or exercise-induced hyperemia. CMD was defined by a microvascular resistance reserve (MRR) < 2.3. Impaired coronary vasodilatation was identified by hyperemic resistance (Rm) ³ 500 WU. NVC was performed to assess cutaneous capillary alterations according to the EULAR classification. Reduced capillary density was defined as < 9 capillaries/mm.
Coronary and NVC assessments were conducted independently by investigators blinded to each other’s results. Associations between coronary and capillary microvascular dysfunction were tested using Fisher’s exact test for small sample sizes. Spearman’s rank correlation was performed to evaluate the association between MRR, hyperemic Rm and nailfold capillary density.
Results: A total of 26 patients with suspected microvascular angina were prospectively included between December 2024 and February 2025. The mean age was 59 years with a predominance of female patients (57.7%, n= 15). Hypertension (50%, n= 13) and dyslipidemia (53.8%, n= 14) were the most prevalent cardiovascular risk factors.
NVC revealed at least one microangiopathic feature in 69.2% of patients (n= 18). The most frequent findings included abnormal capillaries (42.3%, n= 11), reduced capillary loops (38.5%, n= 10), capillary hemorrhages (38.5%, n= 10) and dilated capillaries (34.6%,n= 9) (figure 1).
Capillary rarefaction was observed in a similar proportion of patients with and without CMD (66.7%, n=6/9 vs 64.7%, n=11/17). Among patients with CMD, 50% exhibited impaired coronary vasodilatation (n=4/8).
In patients with capillary rarefaction, 35.3% (n=6/17) had CMD and 23,5% (n=4/17) had impaired coronary vasodilatation (figure 2).
Conclusion: Cutaneous capillary abnormalities were commonly observed in patients with suspected ANOCA. While no statistically significant association was found between capillary rarefaction and CMD, the majority of patients with CMD exhibited capillary rarefaction, suggesting a potential link between coronary and peripheral microvascular dysfunction.
Interestingly, the high prevalence of capillary rarefaction among patients without CMD raises the hypothesis that peripheral microangiopathy may either precede coronary involvement, reflect a more generalized systemic process, or represent a distinct microvascular phenotype.
Further studies in larger cohorts are needed to clarify these relationships and to determine whether specific nailfold capillaroscopic features could serve as a reliable, non-invasive markers of coronary microvascular dysfunction.
Figure 1 : Proportion of nailfold capillary abnormalities in patients with suspected ANOCA
Figure 2 : Correlation between MRR and nailfold capillary density
3 – Computational Fluid Dynamics Analysis of Left Atrial Blood Flow in Patients with Atrial Fibrillation
Louis PARKER
Team: Cardiovascular Imaging – LIB Biomedical Imaging Laboratory Inserm U1146 CNRS UMR 7371
Louis Parker, Emilie Bollache, Jonas Leite, Cristiana Corsi, Shannon Soulez, Khaoula Bouazizi, Jihane Safi, Jacques Feignoux, Olivier Piot, Nicolas Badenco, Estelle Gandjbakhch, Alban Redheuil1, Mikael Laredo, Nadjia Kachenoura.
Introduction: Atrial fibrillation (AF), a common cardiac arrhythmia, disrupts blood flow patterns in the left atrium (LA), increasing the risk of thrombus formation and contributing to the high incidence of stroke in AF patients. While 4D flow MRI provides some flow information, computational fluid dynamics (CFD) enables significantly higher spatial and temporal resolution, allowing for a more detailed analysis of the haemodynamic impact of AF.
Methods: We developed a novel dynamic 3D model of LA flow by integrating 4D flow MRI and CT imaging. Using 224 cores of the MCMeSU supercomputer (Sorbonne Université), we simulated cardiac flow in 26 patients. From these simulations, we extracted velocity, wall shear stress (WSS), and relative residence time (RRT) data in both the LA and the left atrial appendage (LAA).
Results: Consistent with previous studies, the LAA exhibited highly stagnant flow conditions, characterized by significantly lower time-averaged wall shear stress (TAWSS) (p<0.0001), as well as higher oscillatory shear index (OSI) (p<0.0001) and RRT (p<0.0001) compared to the rest of the LA. Additionally, increased indexed LA volume—a marker of progressive atrial wall remodeling—was significantly correlated with increased stasis (RRT) in both the LA (p=0.016) and LAA (p=0.003).
Conclusion: This study presents a novel computational model for high-resolution mapping of LA flow dynamics. Our findings highlight the prothrombotic nature of the LAA and demonstrate that increased LA volume exacerbates flow stasis, reinforcing its potential role in stroke risk
4 – AI-Driven Multimodal Insights in Atrial Cardiomyopathy
Maharajah PONNAIAH
Plateform: ICAN I/O – Data Science
Artificial intelligence is revolutionizing our understanding of atrial cardiomyopathy, a complex and often silent condition that frequently precedes atrial fibrillation (AF) and stroke. By integrating diverse biomedical data sources, including imaging, omics, electrophysiology, and clinical parameters, AI unlocks the potential to detect early biomarkers of atrial remodeling, predict disease progression, and personalize treatment strategies like never before.
At the forefront of this transformation is MAESTRIA (Machine Learning and Artificial Intelligence for Early Detection of Stroke and Atrial Fibrillation), a flagship Horizon 2020 project funded by the European Union. In MAESTRIA, we are developing a cutting-edge AI-powered platform designed to fuse multimodal data for early detection, risk stratification, and precision management of AF and stroke. A cornerstone of this initiative is the digital Demonstrator, now in its prototype phase, which integrates these datasets into an explainable and clinically actionable decision support system.
In parallel, the project is poised to deliver an AI-powered echocardiography pipeline capable of real-time automatic segmentation, cardiac function analysis (e.g., ejection fraction, strain), and image classification. In future phases, this module will be integrated with Virtual and Augmented Reality (VAR) to enable immersive 3D visualization, enhancing clinical interpretation and patient communication.
By combining deep domain expertise with advanced AI and a strong focus on explainability, MAESTRIA aims to uncover novel insights into atrial cardiomyopathy and cardiac remodeling. The outcome will support more accurate, reproducible, and timely diagnostics, paving the way for a new era in precision cardiology.
This presentation will outline our technical roadmap, highlight current progress, and explore the transformative potential of AI-driven multimodal approaches in cardiovascular care.
5 – Boehringer Ingelheim pipeline news and update
Delphine BOUSQUET
National Lead for Scientific Experts – Boehringer Ingelheim
Session – posters
Jury: Michel Zeitouni, Maryse Guérin, Bruno Fève
1 – Decreased adipose tissue gene expression after a 48-week switch from an INSTI regimen to TDF/3TC/DOR
Jennifer GORWOOD
Team: Lipodystrophies, Metabolic & Hormonal Adaptations, and Aging
UMRS_938, Saint-Antoine Research Center (CRSA)
2 – Macrophage-specific Mlkl deletion attenuates hepatic inflammation and necroptosis in metabolic dysfunction-associated steatotic liver disease (MASLD)
Antoine LEFEBVRE
Team: Fibro-inflammatory liver diseases of metabolic and biliary origin
UMRS_938, Saint-Antoine Research Center (CRSA)
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a rapidly growing condition, affecting nearly 30% of the population. In some cases, steatosis can progress to metabolic-associated steatohepatitis (MASH), characterized by liver fibrosis and inflammation. Recent studies have highlighted that cell death, particularly necroptosis, plays a crucial role in disease progression. Necroptosis is mediated by RIPK1, RIPK3 (Receptor-interacting protein kinases), and MLKL (Mixed Lineage Kinase Domain-Like protein), whose expression levels are elevated in steatohepatitis. The objective of this study was to investigate the specific role of MLKL in macrophages on the progression of MASLD and associated metabolic alterations.
Method: We generated a novel mouse model with a macrophage-specific deletion of Mlkl in macrophages (Mlklmacrophages-KO) using the Cre-lox system. Wild-type (WT) and Mlklmacrophages-KO mice were fed either a chow diet or a high-fat diet for 16 weeks starting at 8 weeks of age. Body weight was monitored, and glucose tolerance was assessed using an oral glucose tolerance test. Liver steatosis was evaluated by histological analysis and quantification of intrahepatic triglycerides. Expression of necroptosis mediators was assessed by Western blot, while inflammation and lipid metabolism were evaluated by RT-qPCR.
Results: Mlklmacrophages-KO exhibited no differences in body weight gain or glucose tolerance compared to WT mice. Similarly, liver histology and triglyceride quantification indicated no difference in hepatic fat accumulation between groups. However, inflammatory gene expression analysis revealed decreased expression of markers related to cell death, inflammation, and lipolysis in theMlklmacrophages-KO group. Additionally, a reduction in necroptosis markers RIPK1 and RIPK3 was observed in both the liver and visceral adipose tissue.
Conclusion: The macrophage-specific deletion of Mlkl appears to attenuate hepatic inflammation and cell death independently of obesity or glucose tolerance. The concurrent reduction of necroptosis markers in visceral adipose tissue also suggests a broader anti-inflammatory effect, potentially beneficial for metabolic health.
3 – Consequences of maternal obesity on postnatal cardiac development
Dounia FAHRI
Team: Molecular and Cellular Plasticity in Cardiovascular Diseases
UMRS_1166-ICAN, Cardiovascular and Metabolic Diseases
Introduction: Obesity is a major public health issue, and its rising prevalence contributes to the increased incidence of cardiovascular diseases. The overweight epidemic affects pregnant women, and the uterine environment influences organ development. In particular, children born to obese mothers have higher rates of cardiovascular events and mortality. However, little is known about postnatal cardiac development and the impact of early metabolic dysfunction on the heart’s mechanical and electrical functions. Our objective is to decipher, during postnatal development, the effects of maternal obesity in rats at the functional, structural, transcriptional, and metabolic levels, and to understand the underlying mechanisms.
Materials and Methods: To achieve this, biochemical and omics analyses are performed on offspring hearts at three postnatal developmental stages (P5, P20, and P60). Cardiac function is assessed by echocardiography.
Results: RNA sequencing data show an upregulation of proteins involved in cardiac contraction mechanisms at P20, followed by downregulation at P60, when cardiac function is impaired. A similar pattern is observed in cardiac metabolic pathways, with activation at P5 and P20, followed by downregulation at P60.
Conclusion: In conclusion, these preliminary results suggest that a prenatal obesogenic diet leads to cardiac dysfunction in offspring at the adult stage. These abnormalities appear to be linked to metabolic dysfunction, notably due to excessive exposure to fatty acids during early development.
4 – Targeted gene therapy with the N-terminal fragment of Nav1.5 : A transcomplementation approach to enhance cardiac sodium channel activity in channelopathies
Nathalie NEYROUD
Team: Genomics and Pathophysiology of Myocardial Diseases
UMRS_1166-ICAN, Cardiovascular and Metabolic Diseases
Marie Gizon1, Marine C. Ferrand1, Vincent Fontaine2, Nathalie Mougenot3, Pierre-Léo Laporte1,5, Nathalie Gaborit4, Fabrice Extramiana1,5, Isabelle Baró4, Pascale Guicheney1, Flavien Charpentier4, Nicolas Doisne1, Nathalie Neyroud1
1 Sorbonne Université, INSERM, Research Unit on Cardiovascular and Metabolic Diseases, UMRS-1166, 75013 Paris, France
2 ICANBiocell, Institute of Cardiometabolism And Nutrition (ICAN), 75013 Paris, France
3 Sorbonne Université, UMS-28, 75013 Paris, France
4 Nantes Université, CNRS, INSERM, L’Institut du Thorax, F-44000 Nantes, France
5 Reference Center of Inherited Arrhythmic Syndromes, Bichat Hospital, APHP, Université Paris Cité, 75018 Paris, France
Background: Cardiac channelopathies, caused by mutations in ion-channel genes, can lead to sudden cardiac death (SCD) due to ventricular arrhythmias. Brugada syndrome (BrS) is a rare inherited channelopathy characterized by a unique ECG pattern and a high incidence of ventricular fibrillation leading to SCD in the absence of structural heart defects. The main gene responsible for 20-25% of BrS cases is SCN5A, encoding the cardiac sodium channel alpha-subunit Nav1.5, which carries the sodium current (INa) responsible for the rapid depolarization phase of the action potential (AP). Current treatments do not address the genetic cause of channelopathies; thus, this study explored the therapeutic potential of overexpressing the N-terminal region of Nav1.5 (Nter) to restore electrical activity by rescuing INa, in the context of SCN5A deficiency.
Methods: We overexpressed the Nter peptide using viral vectors in Scn5a+/- mice, in CRISPR/Cas9 edited-SCN5A+/- cardiomyocytes derived from induced-pluripotent stem cells (iPSC-CMs) and in BrS patient iPSC-CMs. We assessed molecular and functional effects of Nter overexpression in vitro and in vivo by measuring Nav1.5 subcellular expression and electrophysiological activity and by recording ECGs and arrhythmias.
Results: Scn5a+/- mice showed impaired INa and AP parameters associated with a slowed-cardiac conduction, characteristic of the BrS phenotype, that were rescued by cardiac-specific overexpression of the Nter. This increase in INa density was caused by a translocation of Nav1.5 to the cell membrane in Nter-overexpressing mice and iPSC-CMs. Most importantly, Nter overexpression normalized atrioventricular and ventricular conduction and protected Scn5a+/- mice from arrhythmias triggered by programmed electrical stimulation. Similarly, Nter overexpression in SCN5A+/- human iPSC-CMs increased Nav1.5 cell-surface expression 2-fold, resulting in normalization of INa and abolition of early after depolarizations recorded in spontaneous APs. Similar results were obtained in iPSC-CMs derived from a BrS patient, confirming the potential of this therapy in human models.
Conclusions: This study identified a novel therapeutic peptide effective in restoring cardiac excitability in animal and cellular models of BrS, paving the way for future development of therapies for life-threatening arrhythmias in patients with SCN5A deficiency.
5 – Epicardial adipose tissue orchestrates the atria remodeling through crosstalk between macrophages and epicardial precursors
Nadine SUFFEE
Team: Molecular and Cellular Plasticity in Cardiovascular Diseases
UMRS_1166-ICAN, Cardiovascular and Metabolic Diseases
6 – Phenotyping heterogeneity of recurrent myocarditis in the AMPHIBIA registry
Mathieu PROUST
Team: Cardiology
BACKGROUND
Recent evidence supports that there is an overlap between recurrent acute myocarditis and genetic arrhythmogenic cardiomyopathy such as desmosomal or titin-related cardiomyopathy. To date, there are limited data on the phenotyping heterogeneity of recurrent myocarditis. The aim of this analysis using the AMPHIBIA registry is to cluster different phenotypes associated with recurrences and evaluate the association between these phenotypes and the risk of outcomes.
METHODS
This is an observational ambispective cohort study based on the AMPHIBIA cohort (NCT04844151), carried out by Assistance Publique – Hôpitaux de Paris and the ACTION Study Group, including patients with proven myocarditis hospitalized between 2008 and 2024 at the Pitié Salpétrière Hospital. The diagnosis of acute myocarditis is based on the presence of acute symptoms, elevated cardiac troponin and the presence of Lake Louise criteria on CMR imaging or histologically proven. Recurrence is defined as at least 2 distinct episodes of acute myocarditis. Key exclusion criteria include the diagnosis of toxic drug-induced myocarditis or the presence of a any other cardiac or extracardiac cause that may explain the clinical presentation. Outcomes include temporary circulatory support implantation, heart transplantation, death, multiples recurrences, arrhythmias, and conduction disorders.
RESULTS
From August 2008 to December 2023, 609 cases of acute myocarditis were included. 26 patients were excluded (immune checkpoint or chemotherapy-related myocarditis, severe coronary artery disease associated…). Among these patients, we identified 71 patients (12%) with recurrent myocarditis (male 75%; median age 28,7 years). The median follow-up was 3,2 years (1,4 – 8,3 years). The median LVEF on admission on trans-thoracic echography was 60%.
7 patients (9,8%) required temporary external hemodynamic support. Detailed phenotypes include three main presentations: idiopathic (73,2%: viral), autoimmune (12,6%: systemic lupus erythematosus, eosinophilic granulomatosis with polyangiitis…), and genetic recurrent myocarditis (7%: desmosomal genes variants…). The features of interest including clinical, biological, etiological, echocardiographic, CMR imaging, genetic and histological data and the rate of outcomes will be available for the ICAN meeting.
CONCLUSIONS
To our knowledge, this will be the first study defining phenotypes associated with recurrent myocarditis. Identifying these phenotypes is crucial to stratify the risk of recurrences and development of genetic cardiomyopathy. These phenotypes may help physicians in guiding the therapeutic managements of these patients.
7 – Nailfold Capillaroscopic Findings in Patients With Suspected Microvascular Angina
Omar EL ZOUHAYRI
Team: Atherothrombosis and Applied Pharmacology
UMRS_1166-ICAN, Cardiovascular and Metabolic Diseases
Background: Coronary microvascular dysfunction (CMD) is a major condition underlying angina with no obstructive coronary arteries (ANOCA). Whether coronary microvascular dysfunction is part of a systemic microvascular disease remains unclear. Nailfold videocapillaroscopy (NVC) offers a non-invasive window into peripheral microcirculation.
Objective: Our study aims to assess whether CMD is associated with nailfold capillary abnormalities in patients with suspected ANOCA.
Methods: This single-center prospective cohort included patients evaluated for ANOCA using invasive coronary microcirculation testing by continuous thermodilution or exercise-induced hyperemia. CMD was defined by a microvascular resistance reserve (MRR) < 2.3. Impaired coronary vasodilatation was identified by hyperemic resistance (Rm) ³ 500 WU. NVC was performed to assess cutaneous capillary alterations according to the EULAR classification. Reduced capillary density was defined as < 9 capillaries/mm.
Coronary and NVC assessments were conducted independently by investigators blinded to each other’s results. Associations between coronary and capillary microvascular dysfunction were tested using Fisher’s exact test for small sample sizes. Spearman’s rank correlation was performed to evaluate the association between MRR, hyperemic Rm and nailfold capillary density.
Results: A total of 26 patients with suspected microvascular angina were prospectively included between December 2024 and February 2025. The mean age was 59 years with a predominance of female patients (57.7%, n= 15). Hypertension (50%, n= 13) and dyslipidemia (53.8%, n= 14) were the most prevalent cardiovascular risk factors.
NVC revealed at least one microangiopathic feature in 69.2% of patients (n= 18). The most frequent findings included abnormal capillaries (42.3%, n= 11), reduced capillary loops (38.5%, n= 10), capillary hemorrhages (38.5%, n= 10) and dilated capillaries (34.6%,n= 9) (figure 1).
Capillary rarefaction was observed in a similar proportion of patients with and without CMD (66.7%, n=6/9 vs 64.7%, n=11/17). Among patients with CMD, 50% exhibited impaired coronary vasodilatation (n=4/8).
In patients with capillary rarefaction, 35.3% (n=6/17) had CMD and 23,5% (n=4/17) had impaired coronary vasodilatation (figure 2).
Conclusion: Cutaneous capillary abnormalities were commonly observed in patients with suspected ANOCA. While no statistically significant association was found between capillary rarefaction and CMD, the majority of patients with CMD exhibited capillary rarefaction, suggesting a potential link between coronary and peripheral microvascular dysfunction.
Interestingly, the high prevalence of capillary rarefaction among patients without CMD raises the hypothesis that peripheral microangiopathy may either precede coronary involvement, reflect a more generalized systemic process, or represent a distinct microvascular phenotype.
Further studies in larger cohorts are needed to clarify these relationships and to determine whether specific nailfold capillaroscopic features could serve as a reliable, non-invasive markers of coronary microvascular dysfunction.
8 – Impact of Clonal Hematopoiesis of Indeterminate Signification on Long Term Prognosis of Premature Coronary Artery Disease
Ghilas RAHOUAL
Team: Atherothrombosis and Applied Pharmacology
UMRS_1166-ICAN, Cardiovascular and Metabolic Diseases
9 – The role of gut microbiota-derived 12-ketolithocholic acid to atherosclerosis progression
Kaidi ZANG
Team: Cellular and Systemic Lipid Metabolism in Cardiometabolic Diseases
UMRS_1166-ICAN, Cardiovascular and Metabolic Diseases
10 – Left Atrium Segmentation Using Deep Learning for Atrial Fibrillation
Jonas LEITE
Team: Cardiovascular Imaging – LIB Biomedical Imaging Laboratory Inserm U1146 CNRS UMR 7371
𝐉𝐨𝐧𝐚𝐬 𝐋𝐞𝐢𝐭𝐞, Tom Da Silva−Faria, Louis Parker, Khaoula Bouazizi, Marie Shannon Soulez, Moussa Gueda Moussa, Mikaël Laredo, Alban Redheuil, Estelle Gandjbakhch, Emilie Bollache, Nadjia Kachenoura
Left atrium (LA) function and hemodynamics accurate assessment is critical for deciphering the complex LA cardiomyopathy, which underlies atrial fibrillation. While cardiac MRI is a comprehensive radiation free imaging modality readily available for LA imaging including anatomical cine SSFP and 4D flow MRI sequences, processing such numerous slices and temporal frames (>2000 images per patient) is time consuming and cumbersome. My presentation will focus on describing deep learning pipelines that I designed during my PhD thesis dedicated to the automated estimation of quantitative LA strain and inner hemodynamics from such MRI images. Results demonstrating robustness and generalizability of our models will be also described.
11 – Incremental value of echocardiography to refine mid-term risk prediction of death in pulmonary embolism using four cardiac chambers myocardial deformation analysis
Laurie SOULAT-DUFOUR
Department : Cardiology, Saint Antoine Hospital
Background: Echocardiography in acute pulmonary embolism (PE) primarily focuses on right ventricle (RV) function. Cardiac cavities morphological and hemodynamic involvement characterization is part of the initial evaluation. We sought to evaluate the prognostic additional value of myocardial strain of right and left cardiac cavities beyond the ESC risk score at mid-term follow up.
Methods: We retrospectively analyzed 488 patients hospitalized for acute PE. Left ventricle (LV), left atrial (LA), right atrial (RA) and RV strain were measured using speckle tracking transthoracic echocardiography (TTE) at admission. Primary outcome was all-cause of mortality.
Results: During a median follow-up of 3.6 (2.7–4.7) years, death occurred in 93 patients. Patients with highest severity of PE according to the ESC risk score had at baseline significantly lower LA (reservoir, conduit, contractile), RA (reservoir, conduit), LV and RV strain values (Figure 1A) . Using receiver operating characteristic analysis, the ESC risk score had the lowest AUC to predict the long-term risk of death; a combined approach including clinical, biological and echo with strain parameters were identified as having the highest predictive value of long-term risk of death (Figure 1B).
Conclusion: Beyond RV cavity remodeling and dysfunction, PE induced acute alteration of the 4 cardiac chambers strains. Strain analysis appears as an interesting new tool in addition to clinical, biological parameters to predict mid-term outcome.
12 – Incremental value of Left Atrial Appendage 3D Echocardiography to refine the Characterization of a Prothrombotic State in Atrial Fibrillation
Laurie SOULAT-DUFOUR
Department : Cardiology, Saint Antoine Hospital
Background: Left atrial (LA) volume is a marker of remodeling, thromboembolic risk, and prognosis in atrial fibrillation (AF). Limited data are available on LA appendage (LAA) volume (LAAV) and function in the characterization of LA/LAA thrombogenicity.
Methods: We prospectively studied 206 patients with AF using 2D transthoracic echocardiography and 2D/3-dimensional (3D) transesophageal echocardiography (TEE) of the LAA (Figure 1A). Patients were stratified according to the presence or absence of LAA sludge and/or thrombus.
Results: Patients with LAA sludge/thrombus (n = 35) had larger LA volume, lower left ventricular ejection fraction, lower LAA emptying and filling flow velocities, larger 2D LAA ostium diameter and area, larger 3D end-systolic (ES) LAA ostium area, and larger 3D LAA volume (LAAV). Patients with LAA sludge/thrombus more frequently had non chicken-wing morphology using 3D TEE. On multivariable logistic regression analysis, LAA emptying flow velocity and 3D ES LAAV were associated with the presence of LAA sludge/thrombus (P < .0001 and P = .031, respectively). Using receiver operating characteristic analysis, 2D and 3D TEE morphological/functional parameters were identified as having the highest predictive value of sludge/thrombus in addition to clinical, biological, and TTE parameters (Figure 1B).
Conclusion: 3D characterization of LAAV depicts a degree of LAA remodeling in atrial fibrillation associated to LAA thrombogenicity.
Figure 1. A. Evaluation of 3D ES LAAV in 3D TEE with Zoom 3D mode 1 beat. B. Receiver operating characteristic curve of presence of sludge/thrombus.
13 – MANDRAGORE : Multimodal (IRM and metabolic) evaluation model of transplanted heart grafts
Elodie BERG
Department : Cardiac Surgery
Acceptance of heart transplants is mainly based on the donor’s medical history (cardiac ultrasound, CT scan). There is currently no reliable assessment of the consequences of ischaemia or perfusion during ex vivo perfusion. Some ex vivo perfusion devices aim to assess grafts on the basis of lactate metabolism, but this remains a very limited and indirect approach.
Currently, there are several methods of preserving cardiac grafts: uncontrolled static hypothermic preservation (icebox), controlled (Paragonix), hypothermic ex vivo perfusion (XVIVO). The exact performance of these devices in terms of preservation quality has not been clearly established and it is not possible to rationalize their use.
The main objectives of this study are to develop an objective and reproducible assessment of cardiac grafts prior to transplantation using cardiac MRI. In addition to detecting ischemic lesions, MRI will provide a metabolic and qualitative assessment of the grafts. The other main objective is to evaluate the different preservation methods on the occurrence of ischemic lesions during the graft transport phase.
The ischemia assessment model will be performed on female pigs of approximately 11 weeks of age (40 kg). We will have a multi-organ procurement (MOP) arm and a Maastricht 3 (M3) arm.
In the M3 arm, we will perform a standard sampling arm and a myocardial disease arm to obtain an MRI correlation. This will allow us to obtain concordance between the induced ischemic lesions and the MRI sequences. These 30-minute sequences will be performed every hour until 6 hours after clamping. These data will be confirmed by metabolomics and lipidomics.
If this assessment proves relevant, it could be incorporated into routine clinical practice as a reliable means of assessing grafts prior to transplantation.
Finally, in its clinical application, this assessment model will make it possible to optimize the cost of graft transport by choosing the most appropriate means of preservation for the transport time in order to limit ischemic damage.
14 – The role of gut microbiota-derived 12-ketolithocholic acid to atherosclerosis progression
Sonny YDE
Team: Metabolic Diseases, Diabetes, and Comorbidities
UMRS_1166-ICAN, Cardiovascular and Metabolic Diseases
Metabolic dysfunction-associated liver disease (MASLD) encompasses a range of pathologies that can begin with steatosis, which can transition to steatohepatitis (MASH) and fibrosis/cirrhosis. Mitochondrial activity, in a broad sense, plays a key role in liver metabolism and, more specifically, in the progression of MASLD. However, the precise aspects of mitochondrial activity contributing to this progression remain debated. In this study, we use a mouse model (LMKO) in which hepatocytes have been deleted of Mitochondrial Fission Process 1 (Mtfp1), which encodes an inner mitochondrial membrane protein with dual functions. Live mitochondria of male LMKO mice show increased Oxidative phosphorylation (OXPHOS) activity and reduced opening of the mitochondrial permeability transition pore (mPTP), which correlates with protection against high-fat diet-induced steatosis and cell death sensitivity, respectively. We are now evaluating whether LMKO mice are protected against MASH induced by a choline-deficient L-amino acid defined high fat diet (CDAA-HFD) . By carrying out studies in both male and female mice, we discovered that the development of fibrosis and hepatic inflammation is influenced by biological sex and is independent of steatosis. We are currently exploring the molecular and cellular mechanisms underlie the protection against MASH observed in LMKO animals. We seek to use LMKO mice to clarify the respective roles of OXPHOS and mPTP opening in hepatic steatosis and its progression to MASH, and provide insights that will benefit the development of targeted treatment strategies.
15 – Automated AI Modeling of Chronotropic Response to Exercise
Rosa TCHALA SARA
Plateform : ICAN I/O – Data Science IHU ICAN
Introduction
The heart’s adaptation to exercise is governed by complexes mechanisms, offering a clear insight into one’s effort tolerance and potential heart failure concerns. During an effort test, the trajectory of heart rate evolution differs among patient profiles, including athletes, individuals with normal cardiac function, and those with heart failure. The aim of this research is to characterize this trajectory and stratify the patients to determine if heart rate evolution during an effort test is indeed a physiological biomarker to identify heart failure.
Materials and Methods:
A total of 2,078 electrocardiogram (ECG) recordings obtained during exercise tests were analysed. Each recording was experimentally annotated with the first and second ventilatory thresholds (VT1 and VT2). Heart failure cases were stratified into three categories based on the Davies test: a p-value > 0.05 indicates a linear heart rate trajectory (single equation), while a p-value < 0.05 suggests at least one segmentation point in the heart rate signal.
Results:
Unsupervised segmentation identified three distinct heart rate trajectory profiles. The primary change point consistently occurred around the VT1, indicating that this threshold is reflected in heart rate dynamics. Incorporating VT1 as a reference allowed clear stratification of heart rate evolution patterns among different patient groups.
Conclusion :
Heart rate trajectory during an effort test exhibits detectable inflection points, particularly around VT1. These findings suggest that VT1, visible in heart rate signals, is a valuable biomarker for characterizing and stratifying heart failure.
16 – Modeling of dilated cardiomyopathy by iPSC-derived cardiomyocytes : a tool to assess patient’s variants
Delphine DESIGAUD
Plateform : ICAN Bio Cell – iPS – IHU ICAN
Delphine Desigaud2, Sibylle Marteau2, Laetitia Duboscq-Bidot1, Vincent Fontaine2, Eric Villard1,2,3, Flavie Ader1,3
1 Sorbonne Université, INSERM, UMR_S 1166, Paris 75013, France
2 ICAN – Institute for Cardiometabolism and Nutrition, Paris 75013, France
3 APHP, Pitié-Salpêtrière University Hospital, Paris 75013, France
Patients genotype is more and more use to adapt the treatment or patient care to an individualized risk. Patients carrying a truncating variant in FLNC gene can develop dilated cardiomyopathy and present a high risk of sudden cardiac death and arrythmias; leading to adapt the patients care. However, not all the patients presented a dilated cardiomyopathy associated with a FLNC variants harboured truncating variants, some of them carried missenses variants or predicted in-frame exon skipping.
In order to argue the involvement of in-frame exon skipping of FLNC gene in dilated cardiomyopathy, we generated several hiPSC-CM lines carrying (frameshift variant corresponding to the classic type of variant associated with dilated cardiomyopathy), and exon skipping (exon X). All the hiPSC lines, as well as the hiPSC-derived cardiomyocytes have been phenotyped. Comparing FLNC-KO lines and exon skipping lines, we will argue the involvement of the in-frame exon skipping in the development of dilated cardiomyopathy. Functional assays will describe the risk for arrythmias to explore if exon skipping lines present severe arrythmias as the FLNC KO lines. All these datas could help to manage the arrythmogenic risk of the patients carrying FLNC in-frame exon skipping.
17 – Human precision cut liver slices (hPCLS): A relevant preclinical model for investigating MASH and liver fibrosis
Lynda AOUDJEHANE
Plateform : ICAN Bio Cell – Human Liver Biology – IHU ICAN
Chronic liver diseases encompass a range of conditions, including Metabolic Associated Fatty Liver Disease (MAFLD), Metabolic Associated Steatohepatitis (MASH), fibrosis, and cirrhosis, which collectively pose significant health challenges worldwide. The lack of preclinical models that recapitulate key aspects of liver pathophysiology is likely contributing to the inefficiency of developing effective treatments. We have developed a preclinical model using organotypic Human Precision Cut Liver Slices “hPCLS”. This model retains the complex physiological architecture of the native liver and therefore could be a valuable ex vivo liver model. hPCLSs were prepared after obtaining from healthy or pathological liver samples and were prepared, cultured and then incubated with different pharmacological treatments against fibrosis or MASH with fibrosis. We found that hPCLS in primary culture remained viable and functionals for up to 72h. Spontaneous fibrosis or MASH was successfully induced during the primary culture of hPCLS from normal or fatty hPCLS, respectively. Normal hPCLS in primary culture develops spontaneous fibrosis as attested by upregulation fibrotic markers. Fatty hPCLS
culture displays characteristics of a MASH phenotype with upregulation of lipid accumulation, a pro-inflammation response. We showed that the treatment of hPCLS from normal or fatty liver samples with different anti-fibrotic or anti-MASH drugs, improved lipid metabolism and downregulated pro-inflammatory response and fibrogenesis, thus confirming the potential of our model as a relevant preclinical model. In conclusion, we developed a preclinical platform using hPCLS ex vivo model for the screening and the validation of compounds with anti-MASH and anti-fibrotic properties.
18 – Vincent FONTAINE
Plateforme ICAN Bio Cell – iPS – IHU ICAN
19 – Lynda AOUDJEHANE
Plateforme ICAN Bio Cell – Human Liver Biology – IHU ICAN
20 – Marie LHOMME & Farid ICHOU
Plateforme ICAN Omics – IHU ICAN
21 – ICONIC
Louise MEYFROIT
Innovation & Research Valorization Division – IHU ICAN
The ICONIC project, born from the collaboration between two national infrastructures—IHU ICAN and CONSTANCES—aims to create a large, certified non-invasive imaging biobank linked to the CONSTANCES cohort. This collection of MRI and ultrasound images, complemented by a biobank, will be analyzed to characterize heart, vessel, and liver function in the French population across all ages and cardiometabolic risk profiles. These innovative data, currently non-existent in France, will enable the creation of a reference imaging cohort for both academic and industrial research on common and rare diseases. The project will thus contribute to the development of a cardiovascular imaging sector by providing resources to French academic and industrial stakeholders (pharmaceuticals, medical devices, software, data, imaging), opening numerous opportunities for national and international public-private partnerships.
22 – MAESTRIA
Louise MEYFROIT
Innovation & Research Valorization Division – IHU ICAN
The overall objective of the MAESTRIA project is to develop a digital diagnostic tool to improve personalized prediction of atrial fibrillation risk and its comorbidities, primarily stroke. This digital tool, called the Demonstrator, will be accessible to external clinicians through a user-friendly interface. The main innovations of the Demonstrator will stem from the development of algorithms that integrate parameters of various types, ranging from foundational knowledge on atrial fibrillation to new clinical diagnostic tools generated by MAESTRIA partners.
23 – MEDITWIN
Arturo HERNANDES CERVANTES
Innovation & Research Valorization Division – IHU ICAN
The Meditwin project aims to create personalized virtual twins of organs, metabolism, and tumors to enhance diagnosis and treatment. These digital models will allow doctors to simulate various disease progression scenarios, helping to optimize patient care in neurology, cardiology, and oncology.
Funded by iDEMO (Bpifrance, 2024), the project is led by a consortium that includes seven University Hospital Institutes (IHUs), the Nantes University Hospital (CHU de Nantes), INRIA, and several partner startups. It is coordinated by Dassault Systèmes and organized around eight use cases, one of which focuses on familial hypercholesterolemia (WP1.UC3).
This particular use case (WP1.UC3) is being developed in collaboration with CHU Nantes, ICAN, the Vision Institute (IHU Foresight), Dassault Systèmes, and INRIA. It aims to improve the monitoring of patients at high cardiovascular risk by integrating clinical, biological, and imaging data.
Initially, the models will be trained using retrospective data from the FH-CALC and SAFIR patient cohorts. To refine and validate the predictive methods developed, additional heterogeneous data will be needed—specifically from patients with familial hypercholesterolemia (FH) (ATHERO-FH and DESTINY-FH) and high-risk individuals (ERICAH and Predirisk).
24 – PEGASE
Aurélie FOUCHER
Innovation & Research Valorization Division – IHU ICAN
The PEGASE study aims to assess the feasibility of prolonged preservation of heart transplants using an ex-vivo perfusion device, its transport from the West Indies, combined with resumption of cardiac function at 2.5 l/min/m² without pharmacological inotropic support or temporary circulatory assistance, within 15 days of transplantation. The poster details the first successful one.
25 – MANDRAGORE
Aurélie FOUCHER
Innovation & Research Valorization Division – IHU ICAN
Acceptance of heart grafts is primarily based on the donor’s medical file, but current methods for assessing ischemia or perfusion during ex vivo perfusion are limited. The MANDRAGORE project aims to use cardiac MRI to objectively evaluate grafts before transplantation and to study the impact of different preservation methods on ischemic lesions. If successful, MRI assessment could become a routine clinical practice, optimizing graft quality and transport costs.
26 – UTHop’IA
Aurélie FOUCHER
Innovation & Research Valorization Division – IHU ICAN
We propose to exploit MIROKI by Enchanted Tools as an assistant to provide Heart Failure patients with information regarding their health condition, surveillance, care, and rehabilitation. The goal is to provide patients with effective interactions that help them to adapt to their new health situation.
27 – Clinical cohort as a central pilar for translational research
Vlad Ratziu & co-workers
Innovation & Research Valorization Division – IHU ICAN
Metabolic-Associated Fatty Liver Disease (MAFLD) is considered the liver manifestation of metabolic syndrome and is now one of the most common causes of chronic liver disease. Steatosis on ultrasound is found in about 30% of individuals in the general population and transaminases are elevated in about 8%. The histological spectrum of MAFLD covers (a) Metabolic-Associated fatty liver (MAFL), (b) steatohepatitis (MASH), which combines lesions of lobular inflammation and hepatocyte ballooning, (c) fibrosis, and (d) cirrhosis. There are uncertainties regarding the natural history and prognosis of MAFLD. In particular, the stratification of patients in whom there is significant inter-individual variability (the severity and speed of disease progression, cases of regression), the prognosis of progression, the progression to cancer, the role of comorbidities or complications, the impact of a therapeutic intervention (drug or surgery) on the course of the disease.
In order to identify predictive factors (histological, genetic, clinical, biological and imaging) of the progression of MAFLD to the most advanced stage (compensated or decompensated cirrhosis, whether or not liver transplantation is required, liver cancer, death), a retrospective and prospective cohort of patients, followed in the gastroenterology department of the Pitié-Salpêtrière hospital group has been set up by Pr Vlad Ratziu and IHU ICAN. This EpOS-LT cohort has been pivotal to attract both important academic and industrial partnerships. Part of this cohort has also been included in the European SLD registry runned by Pr. Quentin Anstee (Newcastle, UK) and has been implicated in the EpOS and LITMUS european projects, and is currently implicated in the EDC-MASLD, LIVERAIM and ARTEMIS european projects. Over the last seven years, through the LITMUS consortium, the diagnostic performance of multiple biomarkers has been assessed, culminating in the acceptance of two leeters of intent by regulatory agencies in USA and Europe and the submission of a detailed Qualification plan for “diagnostic enrichment” to the FDA. In addition, several industrial partners (mainly SMEs) have been using EpOS-LT to further define and validate their most promising candidate innovating biomarkers.
28 – ESSENCE phase 3 study: semaglutide in metabolic steatohepatitis (MASH)
NOVO NORDISK
Session 3 – Fundamental & Translational Cardiovascular Research
Moderators: Laurent KAPPELER et Marie LAGOUGE
1 – Clinical development programme in cardiometabolism
Dr Isabelle Lonjon-Domanec
VP CMR, Novo Nordisk France- Sponsor
2 – Targeted mRNA sequencing and refined bioinformatics pipeline as an innovative way to reclassify splicing variants in Hypertrophic Cardiomyopathies and improve diagnostic yield
Laetitia RIALLAND
Team: Genomics and Pathophysiology of Cardiovascular Diseases
UMRS_1166-ICAN, Cardiovascular and Metabolic Diseases
Laëtitia Rialland1,2 , Emilie Blin2 , Claire Perret1 , Flavie Ader2 , De la Grange Pierre3 ,
Philippe Charron1,4 , Eric Villard1 , Pascale Richard1,2
1INSERM, UMR_S 1166 and ICAN Institute for Cardiometabolism and Nutrition, Faculté de Médecine, Sorbonne Université , PARIS, France,
2APHP- DMU BioGeM, UF Cardiogénétique et Myogénétique Moléculaire et Cellulaire, Service de Biochimie Métabolique, Hôpital Pitié Salpêtrière, PARIS, France,
3Genosplice, PARIS, France,
4Assistance Publique Hôpitaux de Paris (AP HP), Centre de Référence des Maladies Cardiaques héréditaires ou rares, Hôpital Pitié Salpêtrière, PARIS, France
Background: Hypertrophic cardiomyopathies (HCM) are inherited cardiac diseases with an autosomal dominant transmission, among which MYBPC3 is the main causal gene responsible for haplo-insufficiency. RNA splicing variants in MYBPC3 appears to be a prevalent cause of HCM, however RNA analysis is not developed for these diseases because of cardiac tissue unavailability. Thus, these variants are often classified as Variant of Unknown Significance (VUS) and can’t be use for clinical purposes. We propose an enrichment method, as well as refined bioinformatics pipeline, to detect and classify splicing aberrations in MYBPC3 cDNA causing cardiomyopathies from blood cells mRNA.
Material and method: We selected 26 variants (16 intronics and 10 exonics) detected on DNA potentially affecting splicing. PolyA+ RNA purified from venous blood cells was retro-transcribed, captured with optimized design and sequenced on NextSeq550. A specific bio-informatic pipeline was developed to automatically detect splicing events. Results: The gene MYBPC3 was very well covered and interpretable (RPM~6809, Mean depth~2947X). We detect a splice aberration for 19/26 (73%) of cases, consistent with their respective predictive score, among which 6 (32%) creates a novel junction; 8 (42%) modifies the proportional usage of annotated junctions and 5 (26%) leads to the retention of the entire intron. Then, we perform and refined bio-informatic screening that was able to detect all pathogenic events, including intron retention even when no abnormal junction is associated.
Conclusion: Targeted mRNA sequencing from blood cells helps to classify splice affecting variants, thus improving the yield of molecular diagnostic. This method, associated with a specific bio-informatic pipeline is promising and may also be applied as a screening approach expanded to other cardiomyopathy genes.
Fundings: AVIESAN-ITMO Genetique- Genomique-Bioinformatique [ResDiCard project, Rare diseases call].
3 – Distinct role of macrophages in atrial cardiomyopathy associated to obesity
Nadine SUFFEE
Team: Molecular and Cellular Plasticity in Cardiovascular Diseases
UMRS_1166-ICAN, Cardiovascular and Metabolic Diseases
4 – Cardiometabolic trajectories in familial hypercholesterolemia
Antonio GALLO
Unit of Lipidology and Cardiovascular Prevention, Competence Center for Rare Dyslipidemias (CEDRA),
Department of Nutrition, Pitié-Salpêtrière Hospital, APHP
Closing Keynote – Microvascular Endothelial Cells in Adipose Tissue: Exploring their heterogeneity and functional diversity
Moderator: Fabienne Foufelle
Research Director
Institute of Metabolic and Cardiovascular Diseases
Inserm UMR 1297 – University of Toulouse
Biography
Anne Bouloumié is a Research Director at INSERM and leads the DINAMIX team: Adipose Tissues and Vasculo-Metabolic Flexibility at the I2MC in Toulouse. She holds a degree in pharmacology from Paul Sabatier University and earned her PhD in physiology in 1994, followed by postdoctoral training at the Institute for Cardiovascular Physiology in Frankfurt, Germany. A recipient of the prestigious Sofja Kovalevskaja Award (Germany) in 2001 and the INSERM AVENIR program award in 2005, she established independent research teams in both countries.
Anne Bouloumié’s research focuses on the molecular and cellular mechanisms involved in metabolic adaptation associated with natural aging and obesity-accelerated aging. Her team particularly investigates the cellular and functional heterogeneity of different types of white, beige, and brown adipose depots, and their roles in vasculo-metabolic flexibility.
Her areas of expertise include adipose tissue, progenitor cells, immune cells, endothelial cells, adipogenesis, inflammation, fibrosis, senescence, aging, and obesity. Internationally recognized, she serves on several scientific review and editorial boards and has contributed to over 95 major scientific publications. Her work is known for its innovative and multidisciplinary approach, particularly in exploring the roles of endothelial cells in metabolic diseases.
Summary
Microvascular endothelial cells play a critical and often overlooked role in the regulation of fat depot distribution and adipose tissue function. The interaction between endothelial cells and adipocytes influences the regional accumulation of fat and the development of obesity. They contribute to fat depot distribution through mechanisms involving vascularization, inflammation, and the regulation of nutrient exchange according to changes in energy status. Furthermore, endothelial dysfunction including senescence has been implicated in the pathological redistribution of fat, particularly in visceral depots. This presentation will explore the role of the microvascular endothelial cells in determining fat depot repartition, emphasizing their heterogeneity both in phenotypes and functions. By understanding the vascular-adipose interactions, we may uncover novel strategies for modulating fat distribution and improving metabolic health.
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