Team 2: Cardiovascular Structural Diseases

Group leaders: Catherine BOILEAU & Guillaume JONDEAU

LdVAortic root and aortic valves share numerous common structural, physiological, genetic, and pathophysiologic features. Aortic root and heart valves are vascular tissues highly enriched with fibrillar insoluble extracellular matrix components, including proteoglycans, elastin, and collagen — in situ synthesized by stromal cells : myofibroblasts in valves, smooth muscle cells in aorta. Both tissues support the elevated mechanical stress generated by hemodynamics in the human body, including physiological vortices in the valsalva sinus during diastole (depicted by Leornardo Da Vinci 500 years ago; figure) and the impact of the systolic ejected flow on the aortic root. As a consequence, aortic root and valves pathologies share common etiologies including monogenic heritable diseases, such as Marfan syndrome, which is recognized as a pathogenic determinant of aneurysms and dissections of the ascending aorta, but also of valve structural abnormality and dysfunction. In parallel, bicuspid aortic valve, a highly frequent congenital anomaly, is an important anatomic risk factor for development of aortic valve stenosis but also of aneurysms and/or dissections of the aortic root. Structural diseases of aortic root, aneurysms and dissections, and heart valves, stenosis and calcifications, share the common histological feature of areas of mucoid degeneration, determined by genomic/ hemodynamic microenvironment in both these tissues. For example, aneurysms preferentially develop in valsalva sinus in response to Marfan mutations, in relation to physiological vortices, whereas aneurysms develop in the aortic root in bicuspids, in relation to the change of the aortic ring geometry (oval versus round).

Our project is to pursue the discovery of new genes and of genetic modifiers involved in aortic root and valve diseases in human, to decipher the common and different pathophysiology of these diseases, to develop new diagnostic (functional and molecular imaging) and interventional therapeutics and to decrypt the interactions between aortic valves and aortic root.

The new team 2 originated from Team 6 of U698 (C Boileau) with the addition for the valvular disease project of D Messika-Zeitoun, Alec Vahanian, B Iung – new members – and D Himbert (PH) and MP Jacob (DR2 CNRS) from previous teams 5 and 2, respectively.

Family name
First name
Position
Tel
Email
ABI-FADELMariannePRmarianne.abi-fadel@inserm.fr
ABOU KHALILYaraDoctorantyara.abou-khalil@inserm.fr
ANDRIANIRINAMiangalyAImiangaly.andrianirina@inserm.fr
ARNAUDPaulineAHU01.40.25.85.55pauline.arnaud@aphp.fr
AZARYaraDoctorantyara.azar@net.usj.edu.lb
BOILEAUCatherinePUPH101.40.25.75.21catherine.boileau@inserm.fr
EL BITARSandyMCFsandyelbitar@gmail.com
EL KHOURYPetraMCFpetra_khoury@hotmail.com
GHALEBYoumnaMCF01.40.25.75.22youmna.ghaleb@inserm.fr
HANNANadinePH01.49.09.55.97nadine.hanna@aphp.fr
HIMBERTDominiquePH01.40.25.73.25dominique.himbert@aphp.fr
IUNGBernardPUPH1bernard.iung@aphp.fr
JONDEAUGuillaumePUPH101.40.25.68.10guillaume.jondeau@aphp.fr
LE GOFFCarineCR01.40.25.75.21carine.le-goff@inserm.fr
MICHELJean-BaptisteDREM01.40.25.75.26jean-baptiste.michel@inserm.fr
MILLERONOlivierPHolivier.milleron-ext@aphp.fr
MOREIRA FURTADOMelannyM1melannymoreira@gmail.com
MOUGINZakariaDoctorantzakaria.mougin@inserm.fr
PELLENCQuentinDoctorantquentin.pellenc@aphp.fr
RABESJean-PierreMCUPH01.49.09.55.97jean-pierre.rabes@aphp.fr
URENA-ALCAZARMarinaPHmarina.urena-alcazar@aphp.fr
VARRETMathildeCR01.40.25.75.21mathilde.varret@inserm.fr
1.
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Urena M, Himbert D. 2019. Response: Acute haemolysis after transcatheter mitral valve implantation. European Heart Journal 40:491.
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Vahanian A, Urena M, Himbert D. 2019. Transcatheter Mitral Valve Replacement: The End of the Beginning? Journal of the American College of Cardiology 73:1261–1263.
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Urena M, Himbert D, Vahanian A. 2019. Pushing the Boundaries of Transcatheter Mitral Valve Replacement. Journal of the American College of Cardiology 73:2535–2537.
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Prendergast BD, Baumgartner H, Delgado V, Gérard O, Haude M, Himmelmann A, Iung B, Leafstedt M, Lennartz J, Maisano F, Marinelli EA, Modine T, Mueller M, Redwood SR, Rörick O, Sahyoun C, Saillant E, Søndergaard L, Thoenes M, Thomitzek K, Tschernich M, Vahanian A, Wendler O, Zemke EJ, Bax JJ. 2019. Transcatheter heart valve interventions: where are we? Where are we going? European Heart Journal 40:422–440.
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Roos-Hesselink J, Baris L, Johnson M, De Backer J, Otto C, Marelli A, Jondeau G, Budts W, Grewal J, Sliwa K, Parsonage W, Maggioni AP, van Hagen I, Vahanian A, Tavazzi L, Elkayam U, Boersma E, Hall R. 2019. Pregnancy outcomes in women with cardiovascular disease: evolving trends over 10 years in the ESC Registry Of Pregnancy And Cardiac disease (ROPAC). European Heart Journal.
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Piriou N, Al Habash O, Donal E, Senage T, Le Tourneau T, Pattier S, Guyomarch B, Roussel J-C, Trochu JN, Vahanian A, Obadia J-F, Iung B, Guérin P. 2019. The MITRA-HR study: design and rationale of a randomised study of MITRACLIP® transcatheter mitral valve repair in patients with severe primary mitral regurgitation eligible for high-risk surgery. EuroIntervention: Journal of EuroPCR in Collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology.
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Pellenc Q, Roussel A, De Blic R, Girault A, Cerceau P, Ben Abdallah I, Milleron O, Jondeau G, Castier Y. 2019. False lumen embolization in chronic aortic dissection promotes thoracic aortic remodeling at midterm follow-up. Journal of Vascular Surgery.
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Overtchouk P, Guedeney P, Rouanet S, Verhoye JP, Lefevre T, Van Belle E, Eltchaninoff H, Gilard M, Leprince P, Iung B, Barthelemy O, Le Breton H, Souteyrand G, Vicaut E, Montalescot G, Collet J-P. 2019. Long-Term Mortality and Early Valve Dysfunction According to Anticoagulation Use: The FRANCE TAVI Registry. Journal of the American College of Cardiology 73:13–21.
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Morvan M, Arangalage D, Franck G, Perez F, Cattan-Levy L, Codogno I, Jacob-Lenet M-P, Deschildre C, Choqueux C, Even G, Michel J-B, Bäck M, Messika-Zeitoun D, Nicoletti A, Caligiuri G, Laschet J. 2019. Relationship of Iron Deposition to Calcium Deposition in Human Aortic Valve Leaflets. Journal of the American College of Cardiology 73:1043–1054.
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Milleron O, Ropers J, Arnoult F, Bouleti C, Delorme G, Langeois M, Tchitchinadze M, Guien C, Beroud C, Boileau C, Jondeau G. 2019. Clinical Significance of Aortic Root Modification Associated With Bicuspid Aortic Valve in Marfan Syndrome. Circulation Cardiovascular Imaging 12:e008129.
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Martínez-López D, Camafeita E, Cedó L, Roldan-Montero R, Jorge I, García-Marqués F, Gómez-Serrano M, Bonzon-Kulichenko E, Blanco-Vaca F, Blanco-Colio LM, Michel J-B, Escola-Gil JC, Vázquez J, Martin-Ventura JL. 2019. APOA1 oxidation is associated to dysfunctional high-density lipoproteins in human abdominal aortic aneurysm. EBioMedicine.
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Iung B, Bouleti C. 2019. A New Match Between Surgery and Transcatheter Aortic Valve Replacement: Fear the Endocarditis. Journal of the American College of Cardiology 73:1656–1658.
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Iung B, Messika-Zeitoun D. 2019. Transcatheter Mitral Valve Repair in Secondary MR: New Findings and New Challenges. Journal of the American College of Cardiology 73:2133–2134.
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Iung B. 2019. Hospital Resource Use After TAVR: Clinical and Economic Lessons From Merging Large Databases. Journal of the American College of Cardiology 73:1147–1148.
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Hostetler EM, Regalado ES, Guo D-C, Hanna N, Arnaud P, Muiño-Mosquera L, Callewaert BL, Lee K, Leal SM, Wallace SE, Rideout AL, Dyack S, Aatre RD, Boileau C, De Backer J, Jondeau G, Milewicz DM. 2019. SMAD3 pathogenic variants: risk for thoracic aortic disease and associated complications from the Montalcino Aortic Consortium. Journal of Medical Genetics 56:252–260.
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Habib G, Lancellotti P, Erba P-A, Sadeghpour A, Meshaal M, Sambola A, Furnaz S, Citro R, Ternacle J, Donal E, Cosyns B, Popescu B, Iung B, Prendergast B, Laroche C, Tornos P, Pazdernik M, Maggioni A, Gale CP, Investigators E-E. 2019. Cohort profile The ESC-EORP EURO-ENDO (European Infective Endocarditis) registry. European Heart Journal Quality of Care & Clinical Outcomes.
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Himbert D, Urena M, Ducrocq G. 2019. Is Transcatheter Aortic Valve Replacement Becoming the Standard of Care in Octogenarians? Journal of the American Heart Association 8:e011833.
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Grinberg D, Obadia J-F, Iung B. 2019. Percutaneous Repair for Secondary Mitral Regurgitation. Reply. The New England Journal of Medicine 380:1977–1978.
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Gatti G, Chocron S, Obadia J-F, Duval X, Iung B, Alla F, Chirouze C, Lecompte T, Hoen B, Delahaye F, Tattevin P, Le Moing V, Perrotti A, Study A for the, Infectieuse P of IESG– A pour l’Étude et la P de l’Endocadite. 2019. Using surgical risk scores in nonsurgically treated infective endocarditis patients. Hellenic journal of cardiology: HJC = Hellenike kardiologike epitheorese.
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Franck G, Even G, Gautier A, Salinas M, Loste A, Procopio E, Gaston A-T, Morvan M, Dupont S, Deschildre C, Berissi S, Laschet J, Nataf P, Nicoletti A, Michel J-B, Caligiuri G. 2019. Haemodynamic stress-induced breaches of the arterial intima trigger inflammation and drive atherogenesis. European Heart Journal 40:928–937.
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Fischer Q, Himbert D, Bernier M, Urena M, Nunes Ferreira-Neto A, Paradis J-M, Mohammadi S, Iung B, Rodés-Cabau J. 2019. Impact of moderate to severe mitral stenosis in patients undergoing transcatheter aortic valve replacement. International Journal of Cardiology 286:36–42.
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Durand E, Sokoloff A, Urena-Alcazar M, Chevalier B, Chassaing S, Didier R, Tron C, Litzler P-Y, Bouleti C, Himbert D, Hovasse T, Bar O, Avinée G, Iung B, Blanchard D, Gilard M, Cribier A, Lefevre T, Eltchaninoff H. 2019. Assessment of Long-Term Structural Deterioration of Transcatheter Aortic Bioprosthetic Valves Using the New European Definition. Circulation Cardiovascular Interventions 12:e007597.
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Di Filippo M, Varret M, Boehm V, Rabès J-P, Ferkdadji L, Abramowitz L, Dumont S, Lenaerts C, Boileau C, Joly F, Schmitz J, Samson-Bouma M-E, Bonnefont-Rousselot D. 2019. Postprandial lipid absorption in seven heterozygous carriers of deleterious variants of MTTP in two abetalipoproteinemic families. Journal of Clinical Lipidology 13:201–212.
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Bouleti C, Danchin N, Iung B, Daubert C. 2019. Cardiovascular research in France: Evolution of scientific activities and production over the last decade. Archives of Cardiovascular Diseases 112:241–252.
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Bouleti C, Flamant M, Escoubet B, Arnoult F, Milleron O, Vidal-Petiot E, Langeois M, Ou P, Vrtovsnik F, Jondeau G. 2019. Risk of Ascending Aortic Aneurysm in Patients With Autosomal Dominant Polycystic Kidney Disease. The American Journal of Cardiology 123:482–488.
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Arnaud P, Hanna N, Benarroch L, Aubart M, Bal L, Bouvagnet P, Busa T, Dulac Y, Dupuis-Girod S, Edouard T, Faivre L, Gouya L, Lacombe D, Langeois M, Leheup B, Milleron O, Naudion S, Odent S, Tchitchinadze M, Ropers J, Jondeau G, Boileau C. 2019. Genetic diversity and pathogenic variants as possible predictors of severity in a French sample of nonsyndromic heritable thoracic aortic aneurysms and dissections (nshTAAD). Genetics in Medicine: Official Journal of the American College of Medical Genetics.
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van Hagen IM, Thorne SA, Taha N, Youssef G, Elnagar A, Gabriel H, ElRakshy Y, Iung B, Johnson MR, Hall R, Roos-Hesselink JW, Investigators R, Team E. 2018. Pregnancy Outcomes in Women With Rheumatic Mitral Valve Disease: Results From the Registry of Pregnancy and Cardiac Disease. Circulation 137:806–816.
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Vahanian A, Iung B. 2018. Predicting the outcome of degenerative mitral regurgitation: a step forward but still a long way to go! European Heart Journal 39:1292–1294.
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Urena M, Brochet E, Lecomte M, Kerneis C, Carrasco JL, Ghodbane W, Abtan J, Alkhoder S, Raffoul R, Iung B, Nataf P, Vahanian A, Himbert D. 2018. Clinical and haemodynamic outcomes of balloon-expandable transcatheter mitral valve implantation: a 7-year experience. European Heart Journal 39:2679–2689.
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Spaziano M, Lefèvre T, Romano M, Eltchaninoff H, Leprince P, Motreff P, Iung B, Van Belle E, Koning R, Verhoye JP, Gilard M, Garot P, Hovasse T, Le Breton H, Chevalier B. 2018. Transcatheter Aortic Valve Replacement in the Catheterization Laboratory Versus Hybrid Operating Room: Insights From the FRANCE TAVI Registry. JACC Cardiovascular interventions 11:2195–2203.
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Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, Blomström-Lundqvist C, Cífková R, De Bonis M, Iung B, Johnson MR, Kintscher U, Kranke P, Lang IM, Morais J, Pieper PG, Presbitero P, Price S, Rosano GMC, Seeland U, Simoncini T, Swan L, Warnes CA, Group ESD. 2018. 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy. European Heart Journal 39:3165–3241.
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Rodés-Cabau J, Urena M, Nombela-Franco L, Amat-Santos I, Kleiman N, Munoz-Garcia A, Atienza F, Serra V, Deyell MW, Veiga-Fernandez G, Masson J-B, Canadas-Godoy V, Himbert D, Castrodeza J, Elizaga J, Francisco Pascual J, Webb JG, de la Torre JM, Asmarats L, Pelletier-Beaumont E, Philippon F. 2018. Arrhythmic Burden as Determined by Ambulatory Continuous Cardiac Monitoring in Patients With New-Onset Persistent Left Bundle Branch Block Following Transcatheter Aortic Valve Replacement: The MARE Study. JACC Cardiovascular interventions 11:1495–1505.
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Renard M, Francis C, Ghosh R, Scott AF, Witmer PD, Adès LC, Andelfinger GU, Arnaud P, Boileau C, Callewaert BL, Guo D, Hanna N, Lindsay ME, Morisaki H, Morisaki T, Pachter N, Robert L, Van Laer L, Dietz HC, Loeys BL, Milewicz DM, De Backer J. 2018. Clinical Validity of Genes for Heritable Thoracic Aortic Aneurysm and Dissection. Journal of the American College of Cardiology 72:605–615.
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Nguyen V, Michel M, Eltchaninoff H, Gilard M, Dindorf C, Iung B, Mossialos E, Cribier A, Vahanian A, Chevreul K, Messika-Zeitoun D. 2018. Implementation of Transcatheter Aortic Valve Replacement in France. Journal of the American College of Cardiology 71:1614–1627.
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Paven E, Cimadevilla C, Urena M, Dilly M-P, Nataf P, Raffoul R, Himbert D, Vahanian A, Messika-Zeitoun D. 2018. Management of radiation-induced valvular heart disease due to Hodgkin’s Lymphoma in the modern era. EuroIntervention: Journal of EuroPCR in Collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 13:e1771–e1773.