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1. Impact of reduced exposure to calcineurin inhibitors on the development of de novo DSA: a cohort of non-immunized first kidney graft recipients between 2007 and 2014

Author

S. Girerd, J. Schikowski, N. Girerd, K. Duarte, H. Busby, N. Gambier, M. Ladrière, M. Kessler, L. Frimat, and A. Aarnink

Subjects
Kidney transplantation, Calcineurin inhibitors, Donor specific antibodies, Under immunosuppression, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Abstract Background In low-immunological risk kidney transplant recipients (KTRs), reduced exposure to calcineurin inhibitor (CNI) appears particularly attractive for avoiding adverse events, but may increase the risk of developing de novo Donor Specific Antibodies (dnDSA). Methods CNI exposure was retrospectively analyzed in 247 non-HLA immunized first KTRs by taking into account trough levels (C0) collected during follow-up. Reduced exposure to CNI was defined as follows: C0 less than the lower limit of the international targets for ≥50% of follow-up. Results During a mean follow-up of 5.0 ± 2.0 years, 39 patients (15.8%) developed dnDSA (MFI ≥1000). Patients with DSA were significantly younger (46.6 ± 13.8 vs. 51.7 ± 14.0 years, p = 0.039), received more frequently poorly-matched grafts (59% with 6–8 A-B-DR-DQ HLA mismatches vs. 34.6%, p = 0.016) and had more frequently a reduced exposure to CNI (92.3% vs. 62.0%, p = 0.0002). Reduced exposure to CNI was associated with an increased risk of dnDSA (multivariable HR = 9.77, p = 0.002). Reduced exposure to CNI had no effect on patient survival, graft loss from any cause including death, or post-transplant cancer. Conclusions Even in a low-immunological risk population, reduced exposure to CNI is associated with increased risk of dnDSA. Benefits and risks of under-immunosuppression must be carefully evaluated before deciding on CNI minimization.

Published
2018
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4. Long term longevity of defibrillator leads: a prospective follow-up over 25 years

Author

C Davril, N Hammache, H Blangy, L Freysz, K Benali, N Girerd, and N Sadoul

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Funding Acknowledgements Type of funding sources: None. Background The implantable cardioverter defibrillator (ICD) lead is the most fragile part of the device. Several studies have focused on both the longevity of ICD and the factors associated with lead malfunction but long-term data (i.e., ≥ 10 years) are limited. Purpose We report our experience on the very long-term longevity of ICD leads. Methods Data from all patients ≥18 years implanted with an transvenous ICD at our university hospital between 1988 and May 2021 were prospectively collected and analyzed. Follow-up was censored in July 2022. Data included patient characteristics, lead characteristics and follow-up data. The primary endpoint of the study was the survival rate without lead failure defined by the 2017 HR consensus . Factors influencing longevity were analyzed. Results 2093 ICD leads were included in our study. During follow-up (mean = 72.6±56.9 months, range = 11-299), there were 84 lead dysfunction. Lead survival rate was 97% at 5 years, 92% at 10 years, 88% at 15 years and 85% at 24 years respectively. In the multivariate analysis, factors associated with a higher risk of lead dysfunction revealed were: younger age (p = 0.001), channelopathy (p = 0.037), Linox leads (p = 0.041), Riata leads (p = 0.022) and Fidelis leads (p = 0.001). On the other hand, polyurethane coated leads (p < 0.001), Durata leads (p = 0.036), Endotak reliance leads (p = 0.016) and Sprint quattro 6935 leads (p = 0.026) were associated with less lead dysfunction. Conclusion The survival rate of the leads decreased progressively between 1 and 24 years after implantation but the risk of lead rupture seems to be maximal within the first 10 years after implant with little increase thereafter.

Published
2023

12. Proteomic and Mechanistic Analysis of Spironolactone in Patients at Risk for HF

Author

Pierpaolo Pellicori, Blerim Mujaj, Stephane Heymans, Fozia Z Ahmed, N. Girerd, Ping Wang, Arantxa González, Hans-Peter Brunner-La-Rocca, Javier Díez, Franco Cosmi, Frank T. Edelmann, Mark R. Hazebroek, João Pedro Ferreira, Joe Cuthbert, Andrew L. Clark, Johannes Petutschnigg, Mamas A. Mamas, Roberto Latini, Job A J Verdonschot, John G.F. Cleland, Beatrice Mariottoni, Patrick Rossignol, Javed Khan, Jan A. Staessen, Burkert Pieske, Faiez Zannad, Anne Pizard, Stéphanie Grojean, Timothy Collier, Philippe Rouet, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], London School of Hygiene and Tropical Medicine (LSHTM), University of Manchester [Manchester], University of Hull [United Kingdom], Cortona Hospital, Universidad de Navarra [Pamplona] (UNAV), German Heart Institute Berlin, University of Glasgow, Mario Negri Institute, Center for Human Genetics, University of Leuven School of Medicine, SCHOOL of MEDICINE [Louvain], Université Catholique de Louvain = Catholic University of Louvain (UCL)-Université Catholique de Louvain = Catholic University of Louvain (UCL), Centre d'anthropologie et de génomique de Toulouse (CAGT), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Author Disclosures HOMAGE was funded by a grant from the European Union 7th Framework Programme for Research and Technological Development (HEALTH-F7-305507 HOMAGE (EU FP7 305507 http://www.homage-hf.eu). Drs. Ferreira, Rossignol, Girerd, and Zannad are supported by the RHU Fight-HF, a public grant overseen by the French National Research Agency (ANR) as part of the second 'Investissements d’Avenir' program (reference: ANR-15-RHUS-0004), the French PIA project 'Lorraine Université d’Excellence' (reference: ANR-15-IDEX-04-LUE), Contrat de Plan Etat Lorraine IT2MP, and FEDER Lorraine. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), ANR-15-IDEX-0004,LUE,Isite LUE(2015), European Project: 305507,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,HOMAGE(2013), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), DE CARVALHO, Philippe, Combattre l'insuffisance cardiaque - - FIGHT-HF2015 - ANR-15-RHUS-0004 - RHUS - VALID, ISITE - Isite LUE - - LUE2015 - ANR-15-IDEX-0004 - IDEX - VALID, Heart OMics in AGEing - HOMAGE - - EC:FP7:HEALTH2013-02-01 - 2019-01-31 - 305507 - VALID, RS: Carim - H02 Cardiomyopathy, Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), and MUMC+: MA Med Staf Artsass Cardiologie (9)

Subjects
Male, Proteomics, [SDV]Life Sciences [q-bio], Adipokine, Inflammation, 030204 cardiovascular system & hematology, Pharmacology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Mineralocorticoid receptor, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Fibrosis, Renin–angiotensin system, Natriuretic Peptide, Brain, medicine, Humans, 030212 general & internal medicine, Aged, Mineralocorticoid Receptor Antagonists, Heart Failure, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, fibrosis, spironolactone, HEART-FAILURE INSIGHTS, medicine.disease, Brain natriuretic peptide, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, CARDIAC MATRIX BIOMARKERS, [SDV] Life Sciences [q-bio], renin-angiotensin-aldosterone system, chemistry, MYOCARDIAL-INFARCTION, inflammation, Heart failure, Spironolactone, SURVIVAL, EPLERENONE, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, business, heart failure prevention, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

OBJECTIVES This study sought to further understand the mechanisms underlying effect of spironolactone and assessed its impact on multiple plasma protein biomarkers and their respective underlying biologic pathways.BACKGROUND In addition to their beneficial effects in established heart failure (HF), mineralocorticoid receptor antagonists may act upstream on mechanisms, preventing incident HF. In people at risk for developing HF, the HOMAGE (Heart OMics in AGEing) trial showed that spironolactone treatment could provide antifibrotic and antiremodeling effects, potentially slowing the progression to HF.METHODS Baseline, 1-month, and 9-month (or last visit) plasma samples of HOMAGE participants were measured for protein biomarkers (n = 276) by using Olink Proseek-Multiplex cardiovascular and inflammation panels (Olink, Uppsala, Sweden). The effect of spironolactone on biomarkers was assessed by analysis of covariance and explored by knowledgebased network analysis. RESULTS A total of 527 participants were enrolled; 265 were randomized to spironolactone (25 to 50 mg/day) and 262 to standard care ("control"). The median (interquartile range) age was 73 years (69 to 79 years), and 26% were female. Spironolactone reduced biomarkers of collagen metabolism (e.g., COL1A1, MMP-2); brain natriuretic peptide; and biomarkers related to metabolic processes (e.g., PAPPA), inflammation, and thrombosis (e.g., IL17A, VEGF, and urokinase). Spironolactone increased biomarkers that reflect the blockade of the mineralocorticoid receptor (e.g., renin) and increased the levels of adipokines involved in the anti-inflammatory response (e.g., RARRES2) and biomarkers of hemostasis maintenance (e.g., tPA, UPAR), myelosuppressive activity (e.g., CCL16), insulin suppression (e.g., RETN), and inflammatory regulation (e.g., IL-12B).CONCLUSIONS Proteomic analyses suggest that spironolactone exerts pleiotropic effects including reduction in fibrosis, inflammation, thrombosis, congestion, and vascular function improvement, all of which may mediate cardiovascular protective effects, potentially slowing progression toward heart failure. (HOMAGE [Bioprofiling Response to Mineralocorticoid Receptor Antagonists for the Prevention of Heart Failure]; NCT02556450) (C) 2021 by the American College of Cardiology Foundation.

Published
2021

13. Empagliflozin in the treatment of heart failure with reduced ejection fraction in addition to background therapies and therapeutic combinations (EMPEROR-Reduced): a post-hoc analysis of a randomised, double-blind trial

Author

Subodh Verma, Nitish K Dhingra, Javed Butler, Stefan D Anker, Joao Pedro Ferreira, Gerasimos Filippatos, James L Januzzi, Carolyn S P Lam, Naveed Sattar, Barbara Peil, Matias Nordaby, Martina Brueckmann, Stuart J Pocock, Faiez Zannad, Milton Packer, M Packer, S Anker, J Butler, G Filippatos, S Pocock, F Zannad, JP Ferreira, M Brueckmann, J George, W Jamal, FK Welty, M Palmer, T Clayton, KG Parhofer, TR Pedersen, B Greenberg, MA Konstam, KR Lees, P Carson, W Doehner, A Miller, M Haas, S Pehrson, M Komajda, I Anand, J Teerlink, A Rabinstein, T Steiner, H Kamel, G Tsivgoulis, J Lewis, J Freston, N Kaplowitz, J Mann, J Petrie, S Perrone, S Nicholls, S Janssens, E Bocchi, N Giannetti, S Verma, J Zhang, J Spinar, M-F Seronde, M Boehm, B Merkely, V Chopra, M Senni, S Taddi, H Tsutsui, D-J Choi, E Chuquiure, HPB La Rocca, P Ponikowski, JRG Juanatey, I Squire, J Januzzi, I Pina, R Bernstein, A Cheung, J Green, S Kaul, C Lam, G Lip, N Marx, P McCullough, C Mehta, J Rosenstock, N Sattar, B Scirica, S Shah, C Wanner, D Aizenberg, L Cartasegna, F Colombo Berra, H Colombo, M Fernandez Moutin, J Glenny, C Alvarez Lorio, D Anauch, R Campos, A Facta, A Fernandez, R Ahuad Guerrero, L Lobo Márquez, RA Leon de la Fuente, M Mansilla, M Hominal, E Hasbani, M Najenson, G Moises Azize, H Luquez, L Guzman, H Sessa, M Amuchástegui, O Salomone, E Perna, D Piskorz, M Sicer, D Perez de Arenaza, C Zaidman, S Nani, C Poy, J Resk, R Villarreal, C Majul, T Smith Casabella, S Sassone, A Liberman, G Carnero, A Caccavo, M Berli, N Budassi, J Bono, A Alvarisqueta, J Amerena, K Kostner, A Hamilton, A Begg, J Beltrame, D Colquhoun, G Gordon, A Sverdlov, G Vaddadi, J Wong, J Coller, D Prior, A Friart, A Leone, G Vervoort, P Timmermans, P Troisfontaines, C Franssen, T Sarens, H Vandekerckhove, P Van De Borne, F Chenot, J De Sutter, E De Vuyst, P Debonnaire, M Dupont, O Pereira Dutra, LH Canani, MdC Vieira Moreira, W de Souza, LM Backes, L Maia, B De Souza Paolino, ER Manenti, W Saporito, F Villaça Guimarães Filho, T Franco Hirakawa, LA Saliba, FC Neuenschwander, CA de Freitas Zerbini, G Gonçalves, Y Gonçalves Mello, J Ascenção de Souza, L Beck da Silva Neto, EA Bocchi, J Da Silveira, JB de Moura Xavier Moraes Junior, JD de Souza Neto, M Hernandes, HC Finimundi, CR Sampaio, E Vasconcellos, FJ Neves Mancuso, MM Noya Rabelo, M Rodrigues Bacci, F Santos, M Vidotti, MV Simões, FL Gomes, C Vieira Nascimento, D Precoma, FA Helfenstein Fonseca, JA Ribas Fortes, PE Leães, D Campos de Albuquerque, JF Kerr Saraiva, S Rassi, FA Alves da Costa, G Reis, S Zieroth, D Dion, D Savard, R Bourgeois, C Constance, K Anderson, M-H Leblanc, D Yung, E Swiggum, L Pliamm, Y Pesant, B Tyrrell, T Huynh, J Spiegelman, J-P Lavoie, M Hartleib, R Bhargava, L Straatman, S Virani, A Costa-Vitali, L Hill, M Heffernan, Y Khaykin, J Ricci, M Senaratne, A Zhai, B Lubelsky, M Toma, L Yao, R McKelvie, L Noronha, M Babapulle, A Pandey, G Curnew, A Lavoie, J Berlingieri, S Kouz, E Lonn, R Chehayeb, Y Zheng, Y Sun, H Cui, Z Fan, X Han, X Jiang, Q Tang, J Zhou, Z Zheng, X Zhang, N Zhang, Y Zhang, A Shen, J Yu, J Ye, Y Yao, J Yan, X Xu, Z Wang, J Ma, Y Li, S Li, S Lu, X Kong, Y Song, G Yang, Z Yao, Y Pan, X Guo, Z Sun, Y Dong, J Zhu, D Peng, Z Yuan, J Lin, Y Yin, O Jerabek, H Burianova, T Fiala, J Hubac, O Ludka, Z Monhart, P Vodnansky, K Zeman, D Foldyna, J Krupicka, I Podpera, L Busak, M Radvan, Z Vomacka, R Prosecky, R Cifkova, V Durdil, J Vesely, J Vaclavik, P Cervinka, A Linhart, T Brabec, R Miklik, H Bourhaial, H-G Olbrich, S Genth-Zotz, E Kemala, B Lemke, M Böhm, S Schellong, W Rieker, T Heitzer, H Ince, M Faghih, A Birkenfeld, A Begemann, A Ghanem, A Ujeyl, S von Haehling, T Dorsel, J Bauersachs, M Prull, F Weidemann, H Darius, G Nickenig, A Wilke, J Sauter, U Rauch-Kroehnert, N Frey, CP Schulze, W König, L Maier, F Menzel, N Proskynitopoulos, H-H Ebert, H-E Sarnighausen, H-D Düngen, M Licka, C Stellbrink, B Winkelmann, N Menck, JL López-Sendón, L de la Fuente Galán, JF Delgado Jiménez, N Manito Lorite, M Pérez de Juan Romero, E Galve Basilio, F Cereto Castro, JR González Juanatey, JJ Gómez, M Sanmartín Fernández, X Garcia-Moll Marimon, D Pascual Figal, R Bover Freire, E Bonnefoy Cudraz, A Jobbe Duval, D Tomasevic, G Habib, R Isnard, F Picard, P Khanoyan, J-L Dubois-Rande, M Galinier, F Roubille, J Alexandre, D Babuty, N Delarche, J-B Berneau, N Girerd, M Saxena, G Rosano, Z Yousef, C Clifford, C Arden, A Bakhai, C Boos, G Jenkins, C Travill, D Price, L Koenyves, F Lakatos, A Matoltsy, E Noori, Z Zilahi, P Andrassy, S Kancz, G Simon, T Sydo, A Vorobcsuk, RG Kiss, K Toth, I Szakal, L Nagy, T Barany, A Nagy, E Szolnoki, VK Chopra, S Mandal, V Rastogi, B Shah, A Mullasari, J Shankar, V Mehta, A Oomman, U Kaul, S Komarlu, D Kahali, A Bhagwat, V Vijan, NK Ghaisas, A Mehta, J Kashyap, Y Kothari, S TaddeI, M Scherillo, V Zacà, S Genovese, A Salvioni, A Fucili, F Fedele, F Cosmi, M Volpe, C Mazzone, G Esposito, M Doi, H Yamamoto, S Sakagami, S Oishi, Y Yasaka, H Tsuboi, Y Fujino, S Matsuoka, Y Watanabe, T Himi, T Ide, M Ichikawa, Y Kijima, T Koga, S Yuda, K Fukui, T Kubota, M Manita, H Fujinaga, T Matsumura, Y Fukumoto, R Kato, Y Kawai, G Hiasa, Y Kazatani, M Mori, A Ogimoto, M Inoko, M Oguri, M Kinoshita, K Okuhara, N Watanabe, Y Ono, K Otomo, Y Sato, T Matsunaga, A Takaishi, N Miyagi, H Uehara, H Takaishi, H Urata, T Kataoka, H Matsubara, T Matsumoto, T Suzuki, N Takahashi, M Imamaki, T Yoshitama, T Saito, H Sekino, Y Furutani, M Koda, T Shinozaki, K Hirabayashi, R Tsunoda, K Yonezawa, H Hori, M Yagi, M Arikawa, T Hashizume, R Ishiki, T Koizumi, K Nakayama, S Taguchi, M Nanasato, Y Yoshida, S Tsujiyama, T Nakamura, K Oku, M Shimizu, M Suwa, Y Momiyama, H Sugiyama, K Kobayashi, S Inoue, T Kadokami, K Maeno, K Kawamitsu, Y Maruyama, A Nakata, T Shibata, A Wada, H-J Cho, JO Na, B-S Yoo, J-O Choi, SK Hong, J-H Shin, M-C Cho, SH Han, J-O Jeong, J-J Kim, SM Kang, D-S Kim, MH Kim, G Llamas Esperon, J Illescas Díaz, P Fajardo Campos, J Almeida Alvarado, A Bazzoni Ruiz, J Echeverri Rico, I Lopez Alcocer, L Valle Molina, C Hernandez Herrera, C Calvo Vargas, FG Padilla Padilla, I Rodriguez Briones, EJJR Chuquiure Valenzuela, ME Aguilera Real, J Carrillo Calvillo, M Alpizar Salazar, JL Cervantes Escárcega, R Velasco Sanchez, N Al - Windy, L van Heerebeek, L Bellersen, H-P Brunner-La Rocca, J Post, GCM Linssen, M van de Wetering, R Peters, R van Stralen, R Groutars, P Smits, A Yilmaz, WEM Kok, P Van der Meer, P Dijkmans, R Troquay, AP van Alem, R Van de Wal, L Handoko, ICD Westendorp, PFMM van Bergen, BJWM Rensing, P Hoogslag, B Kietselaer, JA Kragten, FR den Hartog, A Alings, L Danilowicz-Szymanowicz, G Raczak, W Piesiewicz, W Zmuda, W Kus, P Podolec, W Musial, G Drelich, G Kania, P Miekus, S Mazur, A Janik, J Spyra, J Peruga, P Balsam, B Krakowiak, J Szachniewicz, M Ginel, J Grzybowski, W Chrustowski, P Wojewoda, A Kalinka, A Zurakowski, R Koc, M Debinski, W Fil, M Kujawiak, J Forys, M Kasprzak, M Krol, P Michalski, E Mirek-Bryniarska, K Radwan, G Skonieczny, K Stania, G Skoczylas, A Madej, J Jurowiecki, B Firek, B Wozakowska-Kaplon, K Cymerman, J Neutel, K Adams, P Balfour, A Deswal, A Djamson, P Duncan, M Hong, C Murray, D Rinde-Hoffman, S Woodhouse, R MacNevin, B Rama, C Broome-Webster, S Kindsvater, D Abramov, M Barettella, S Pinney, J Herre, A Cohen, K Vora, K Challappa, S West, S Baum, J Cox, S Jani, A Karim, A Akhtar, O Quintana, L Paukman, R Goldberg, Z Bhatti, M Budoff, E Bush, A Potler, R Delgado, B Ellis, J Dy, J Fialkow, R Sangrigoli, K Ferdinand, C East, S Falkowski, S Donahoe, R Ebrahimi, G Kline, B Harris, R Khouzam, N Jaffrani, N Jarmukli, N Kazemi, M Koren, K Friedman, W Herzog, J Silva Enciso, D Cheung, M Grover-McKay, P Hauptman, D Mikhalkova, V Hegde, J Hodsden, S Khouri, F McGrew, R Littlefield, P Bradley, B McLaurin, S Lupovitch, I Labin, V Rao, M Leithe, M Lesko, N Lewis, D Lombardo, S Mahal, V Malhotra, I Dauber, A Banerjee, J Needell, G Miller, L Paladino, K Munuswamy, M Nanna, E McMillan, M Mumma, M Napoli, W Nelson, T O'Brien, A Adlakha, A Onwuanyi, H Serota, J Schmedtje, A Paraschos, R Potu, C Sai-Sudhakar, M Saltzberg, A Sauer, P Shah, H Skopicki, H Bui, K Carr, G Stevens, N Tahirkheli, J Tallaj, K Yousuf, B Trichon, J Welker, P Tolerico, A Vest, R Vivo, X Wang, R Abadier, S Dunlap, N Weintraub, A Malik, P Kotha, V Zaha, G Kim, N Uriel, T Greene, A Salacata, R Arora, R Gazmuri, J Kobayashi, B Iteld, R Vijayakrishnan, R Dab, Z Mirza, V Marques, M Nallasivan, D Bensimhon, B Peart, H Saint-Jacques, K Barringhaus, J Contreras, A Gupta, S Koneru, V Nguyen, Verma, S, Dhingra, N, Butler, J, Anker, S, Ferreira, J, Filippatos, G, Januzzi, J, Lam, C, Sattar, N, Peil, B, Nordaby, M, Brueckmann, M, Pocock, S, Zannad, F, Packer, M, George, J, Jamal, W, Welty, F, Palmer, M, Clayton, T, Parhofer, K, Pedersen, T, Greenberg, B, Konstam, M, Lees, K, Carson, P, Doehner, W, Miller, A, Haas, M, Pehrson, S, Komajda, M, Anand, I, Teerlink, J, Rabinstein, A, Steiner, T, Kamel, H, Tsivgoulis, G, Lewis, J, Freston, J, Kaplowitz, N, Mann, J, Petrie, J, Perrone, S, Nicholls, S, Janssens, S, Bocchi, E, Giannetti, N, Zhang, J, Spinar, J, Seronde, M, Boehm, M, Merkely, B, Chopra, V, Senni, M, Taddi, S, Tsutsui, H, Choi, D, Chuquiure, E, La Rocca, H, Ponikowski, P, Juanatey, J, Squire, I, Pina, I, Bernstein, R, Cheung, A, Green, J, Kaul, S, Lip, G, Marx, N, Mccullough, P, Mehta, C, Rosenstock, J, Scirica, B, Shah, S, Wanner, C, Aizenberg, D, Cartasegna, L, Colombo Berra, F, Colombo, H, Fernandez Moutin, M, Glenny, J, Alvarez Lorio, C, Anauch, D, Campos, R, Facta, A, Fernandez, A, Ahuad Guerrero, R, Lobo Marquez, L, Leon de la Fuente, R, Mansilla, M, Hominal, M, Hasbani, E, Najenson, M, Moises Azize, G, Luquez, H, Guzman, L, Sessa, H, Amuchastegui, M, Salomone, O, Perna, E, Piskorz, D, Sicer, M, Perez de Arenaza, D, Zaidman, C, Nani, S, Poy, C, Resk, J, Villarreal, R, Majul, C, Smith Casabella, T, Sassone, S, Liberman, A, Carnero, G, Caccavo, A, Berli, M, Budassi, N, Bono, J, Alvarisqueta, A, Amerena, J, Kostner, K, Hamilton, A, Begg, A, Beltrame, J, Colquhoun, D, Gordon, G, Sverdlov, A, Vaddadi, G, Wong, J, Coller, J, Prior, D, Friart, A, Leone, A, Vervoort, G, Timmermans, P, Troisfontaines, P, Franssen, C, Sarens, T, Vandekerckhove, H, Van De Borne, P, Chenot, F, De Sutter, J, De Vuyst, E, Debonnaire, P, Dupont, M, Pereira Dutra, O, Canani, L, Vieira Moreira, M, de Souza, W, Backes, L, Maia, L, De Souza Paolino, B, Manenti, E, Saporito, W, Villaca Guimaraes Filho, F, Franco Hirakawa, T, Saliba, L, Neuenschwander, F, de Freitas Zerbini, C, Goncalves, G, Goncalves Mello, Y, Ascencao de Souza, J, Beck da Silva Neto, L, Da Silveira, J, de Moura Xavier Moraes Junior, J, de Souza Neto, J, Hernandes, M, Finimundi, H, Sampaio, C, Vasconcellos, E, Neves Mancuso, F, Noya Rabelo, M, Rodrigues Bacci, M, Santos, F, Vidotti, M, Simoes, M, Gomes, F, Vieira Nascimento, C, Precoma, D, Helfenstein Fonseca, F, Ribas Fortes, J, Leaes, P, Campos de Albuquerque, D, Kerr Saraiva, J, Rassi, S, Alves da Costa, F, Reis, G, Zieroth, S, Dion, D, Savard, D, Bourgeois, R, Constance, C, Anderson, K, Leblanc, M, Yung, D, Swiggum, E, Pliamm, L, Pesant, Y, Tyrrell, B, Huynh, T, Spiegelman, J, Lavoie, J, Hartleib, M, Bhargava, R, Straatman, L, Virani, S, Costa-Vitali, A, Hill, L, Heffernan, M, Khaykin, Y, Ricci, J, Senaratne, M, Zhai, A, Lubelsky, B, Toma, M, Yao, L, Mckelvie, R, Noronha, L, Babapulle, M, Pandey, A, Curnew, G, Lavoie, A, Berlingieri, J, Kouz, S, Lonn, E, Chehayeb, R, Zheng, Y, Sun, Y, Cui, H, Fan, Z, Han, X, Jiang, X, Tang, Q, Zhou, J, Zheng, Z, Zhang, X, Zhang, N, Zhang, Y, Shen, A, Yu, J, Ye, J, Yao, Y, Yan, J, Xu, X, Wang, Z, Ma, J, Li, Y, Li, S, Lu, S, Kong, X, Song, Y, Yang, G, Yao, Z, Pan, Y, Guo, X, Sun, Z, Dong, Y, Zhu, J, Peng, D, Yuan, Z, Lin, J, Yin, Y, Jerabek, O, Burianova, H, Fiala, T, Hubac, J, Ludka, O, Monhart, Z, Vodnansky, P, Zeman, K, Foldyna, D, Krupicka, J, Podpera, I, Busak, L, Radvan, M, Vomacka, Z, Prosecky, R, Cifkova, R, Durdil, V, Vesely, J, Vaclavik, J, Cervinka, P, Linhart, A, Brabec, T, Miklik, R, Bourhaial, H, Olbrich, H, Genth-Zotz, S, Kemala, E, Lemke, B, Bohm, M, Schellong, S, Rieker, W, Heitzer, T, Ince, H, Faghih, M, Birkenfeld, A, Begemann, A, Ghanem, A, Ujeyl, A, von Haehling, S, Dorsel, T, Bauersachs, J, Prull, M, Weidemann, F, Darius, H, Nickenig, G, Wilke, A, Sauter, J, Rauch-Kroehnert, U, Frey, N, Schulze, C, Konig, W, Maier, L, Menzel, F, Proskynitopoulos, N, Ebert, H, Sarnighausen, H, Dungen, H, Licka, M, Stellbrink, C, Winkelmann, B, Menck, N, Lopez-Sendon, J, de la Fuente Galan, L, Delgado Jimenez, J, Manito Lorite, N, Perez de Juan Romero, M, Galve Basilio, E, Cereto Castro, F, Gonzalez Juanatey, J, Gomez, J, Sanmartin Fernandez, M, Garcia-Moll Marimon, X, Pascual Figal, D, Bover Freire, R, Bonnefoy Cudraz, E, Jobbe Duval, A, Tomasevic, D, Habib, G, Isnard, R, Picard, F, Khanoyan, P, Dubois-Rande, J, Galinier, M, Roubille, F, Alexandre, J, Babuty, D, Delarche, N, Berneau, J, Girerd, N, Saxena, M, Rosano, G, Yousef, Z, Clifford, C, Arden, C, Bakhai, A, Boos, C, Jenkins, G, Travill, C, Price, D, Koenyves, L, Lakatos, F, Matoltsy, A, Noori, E, Zilahi, Z, Andrassy, P, Kancz, S, Simon, G, Sydo, T, Vorobcsuk, A, Kiss, R, Toth, K, Szakal, I, Nagy, L, Barany, T, Nagy, A, Szolnoki, E, Mandal, S, Rastogi, V, Shah, B, Mullasari, A, Shankar, J, Mehta, V, Oomman, A, Kaul, U, Komarlu, S, Kahali, D, Bhagwat, A, Vijan, V, Ghaisas, N, Mehta, A, Kashyap, J, Kothari, Y, Taddei, S, Scherillo, M, Zaca, V, Genovese, S, Salvioni, A, Fucili, A, Fedele, F, Cosmi, F, Volpe, M, Mazzone, C, Esposito, G, Doi, M, Yamamoto, H, Sakagami, S, Oishi, S, Yasaka, Y, Tsuboi, H, Fujino, Y, Matsuoka, S, Watanabe, Y, Himi, T, Ide, T, Ichikawa, M, Kijima, Y, Koga, T, Yuda, S, Fukui, K, Kubota, T, Manita, M, Fujinaga, H, Matsumura, T, Fukumoto, Y, Kato, R, Kawai, Y, Hiasa, G, Kazatani, Y, Mori, M, Ogimoto, A, Inoko, M, Oguri, M, Kinoshita, M, Okuhara, K, Watanabe, N, Ono, Y, Otomo, K, Sato, Y, Matsunaga, T, Takaishi, A, Miyagi, N, Uehara, H, Takaishi, H, Urata, H, Kataoka, T, Matsubara, H, Matsumoto, T, Suzuki, T, Takahashi, N, Imamaki, M, Yoshitama, T, Saito, T, Sekino, H, Furutani, Y, Koda, M, Shinozaki, T, Hirabayashi, K, Tsunoda, R, Yonezawa, K, Hori, H, Yagi, M, Arikawa, M, Hashizume, T, Ishiki, R, Koizumi, T, Nakayama, K, Taguchi, S, Nanasato, M, Yoshida, Y, Tsujiyama, S, Nakamura, T, Oku, K, Shimizu, M, Suwa, M, Momiyama, Y, Sugiyama, H, Kobayashi, K, Inoue, S, Kadokami, T, Maeno, K, Kawamitsu, K, Maruyama, Y, Nakata, A, Shibata, T, Wada, A, Cho, H, Na, J, Yoo, B, Choi, J, Hong, S, Shin, J, Cho, M, Han, S, Jeong, J, Kim, J, Kang, S, Kim, D, Kim, M, Llamas Esperon, G, Illescas Diaz, J, Fajardo Campos, P, Almeida Alvarado, J, Bazzoni Ruiz, A, Echeverri Rico, J, Lopez Alcocer, I, Valle Molina, L, Hernandez Herrera, C, Calvo Vargas, C, Padilla Padilla, F, Rodriguez Briones, I, Chuquiure Valenzuela, E, Aguilera Real, M, Carrillo Calvillo, J, Alpizar Salazar, M, Cervantes Escarcega, J, Velasco Sanchez, R, Al - Windy, N, van Heerebeek, L, Bellersen, L, Brunner-La Rocca, H, Post, J, Linssen, G, van de Wetering, M, Peters, R, van Stralen, R, Groutars, R, Smits, P, Yilmaz, A, Kok, W, Van der Meer, P, Dijkmans, P, Troquay, R, van Alem, A, Van de Wal, R, Handoko, L, Westendorp, I, van Bergen, P, Rensing, B, Hoogslag, P, Kietselaer, B, Kragten, J, den Hartog, F, Alings, A, Danilowicz-Szymanowicz, L, Raczak, G, Piesiewicz, W, Zmuda, W, Kus, W, Podolec, P, Musial, W, Drelich, G, Kania, G, Miekus, P, Mazur, S, Janik, A, Spyra, J, Peruga, J, Balsam, P, Krakowiak, B, Szachniewicz, J, Ginel, M, Grzybowski, J, Chrustowski, W, Wojewoda, P, Kalinka, A, Zurakowski, A, Koc, R, Debinski, M, Fil, W, Kujawiak, M, Forys, J, Kasprzak, M, Krol, M, Michalski, P, Mirek-Bryniarska, E, Radwan, K, Skonieczny, G, Stania, K, Skoczylas, G, Madej, A, Jurowiecki, J, Firek, B, Wozakowska-Kaplon, B, Cymerman, K, Neutel, J, Adams, K, Balfour, P, Deswal, A, Djamson, A, Duncan, P, Hong, M, Murray, C, Rinde-Hoffman, D, Woodhouse, S, Macnevin, R, Rama, B, Broome-Webster, C, Kindsvater, S, Abramov, D, Barettella, M, Pinney, S, Herre, J, Cohen, A, Vora, K, Challappa, K, West, S, Baum, S, Cox, J, Jani, S, Karim, A, Akhtar, A, Quintana, O, Paukman, L, Goldberg, R, Bhatti, Z, Budoff, M, Bush, E, Potler, A, Delgado, R, Ellis, B, Dy, J, Fialkow, J, Sangrigoli, R, Ferdinand, K, East, C, Falkowski, S, Donahoe, S, Ebrahimi, R, Kline, G, Harris, B, Khouzam, R, Jaffrani, N, Jarmukli, N, Kazemi, N, Koren, M, Friedman, K, Herzog, W, Silva Enciso, J, Cheung, D, Grover-McKay, M, Hauptman, P, Mikhalkova, D, Hegde, V, Hodsden, J, Khouri, S, Mcgrew, F, Littlefield, R, Bradley, P, Mclaurin, B, Lupovitch, S, Labin, I, Rao, V, Leithe, M, Lesko, M, Lewis, N, Lombardo, D, Mahal, S, Malhotra, V, Dauber, I, Banerjee, A, Needell, J, Miller, G, Paladino, L, Munuswamy, K, Nanna, M, Mcmillan, E, Mumma, M, Napoli, M, Nelson, W, O'Brien, T, Adlakha, A, Onwuanyi, A, Serota, H, Schmedtje, J, Paraschos, A, Potu, R, Sai-Sudhakar, C, Saltzberg, M, Sauer, A, Shah, P, Skopicki, H, Bui, H, Carr, K, Stevens, G, Tahirkheli, N, Tallaj, J, Yousuf, K, Trichon, B, Welker, J, Tolerico, P, Vest, A, Vivo, R, Wang, X, Abadier, R, Dunlap, S, Weintraub, N, Malik, A, Kotha, P, Zaha, V, Kim, G, Uriel, N, Greene, T, Salacata, A, Arora, R, Gazmuri, R, Kobayashi, J, Iteld, B, Vijayakrishnan, R, Dab, R, Mirza, Z, Marques, V, Nallasivan, M, Bensimhon, D, Peart, B, Saint-Jacques, H, Barringhaus, K, Contreras, J, Gupta, A, Koneru, S, Nguyen, V, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)

Subjects
Male, medicine.medical_specialty, Angiotensin receptor, Glucoside, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Adrenergic beta-Antagonists, Angiotensin-Converting Enzyme Inhibitors, 030204 cardiovascular system & hematology, Placebo, 03 medical and health sciences, Angiotensin Receptor Antagonists, 0302 clinical medicine, Endocrinology, Mineralocorticoid receptor, Glucosides, Double-Blind Method, Internal medicine, Post-hoc analysis, Internal Medicine, medicine, Empagliflozin, Humans, 030212 general & internal medicine, Benzhydryl Compounds, ComputingMilieux_MISCELLANEOUS, Aged, Benzhydryl Compound, Heart Failure, Ejection fraction, business.industry, Angiotensin Receptor Antagonist, Adrenergic beta-Antagonist, Angiotensin-Converting Enzyme Inhibitor, Stroke Volume, medicine.disease, 3. Good health, Heart failure, ACE inhibitor, Female, Hypotension, business, medicine.drug, Human
Abstract

Contains fulltext : 249977.pdf (Publisher’s version ) (Closed access) BACKGROUND: It is important to evaluate whether a new treatment for heart failure with reduced ejection fraction (HFrEF) provides additive benefit to background foundational treatments. As such, we aimed to evaluate the efficacy and safety of empagliflozin in patients with HFrEF in addition to baseline treatment with specific doses and combinations of disease-modifying therapies. METHODS: We performed a post-hoc analysis of the EMPEROR-Reduced randomised, double-blind, parallel-group trial, which took place in 520 centres (hospitals and medical clinics) in 20 countries in Asia, Australia, Europe, North America, and South America. Patients with New York Heart Association (NYHA) classification II-IV with an ejection fraction of 40% or less were randomly assigned (1:1) to receive the addition of either oral empagliflozin 10 mg per day or placebo to background therapy. The primary composite outcome was cardiovascular death and heart failure hospitalisation; the secondary outcome was total heart failure hospital admissions. An extended composite outcome consisted of inpatient and outpatient HFrEF events was also evaluated. Outcomes were analysed according to background use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs) or angiotensin receptor neprilysin inhibitors (ARNIs), as well as β blockers and mineralocorticoid receptor antagonists (MRAs) at less than 50% or 50% or more of target doses and in various combinations. This study is registered with ClinicalTrials.gov, NCT03057977. FINDINGS: In this post-hoc analysis of 3730 patients (mean age 66·8 years [SD 11·0], 893 [23·9%] women; 1863 [49·9%] in the empagliflozin group, 1867 [50·1%] in the placebo group) assessed between March 6, 2017, and May 28, 2020, empagliflozin reduced the risk of the primary outcome (361 in 1863 participants in the empagliflozin group and 462 of 1867 in the placebo group; HR 0·75 [95% CI 0·65-0·86]) regardless of background therapy or its target doses for ACE inhibitors or ARBs at doses of less than 50% of the target dose (HR 0·85 [0·69-1·06]) and for doses of 50% or more of the target dose (HR 0·67 [0·52-0·88]; p(interaction)=0·18). A similar result was seen for β blockers at doses of less than 50% of the target dose (HR 0·66 [0·54-0·80]) and for doses of 50% or more of the target dose (HR 0·81 [0·66-1·00]; p(interaction)=0·15). Empagliflozin also reduced the risk of the primary outcome irrespective of background use of triple therapy with an ACE inhibitor, ARB, or ARNI plus β blocker plus MRA (given combination HR 0·73 [0·61-0·88]; not given combination HR 0·76 [0·62-0·94]; p(interaction)=0·77). Similar patterns of benefit were observed for the secondary and extended composite outcomes. Empagliflozin was well tolerated and rates of hypotension, symptomatic hypotension, and hyperkalaemia were similar across all subgroups. INTERPRETATION: Empagliflozin reduced serious heart failure outcomes across doses and combinations of disease-modifying therapies for HFrEF. Clinically, these data suggest that empagliflozin might be considered as a foundational therapy in patients with HFrEF regardless of their existing background therapy. FUNDING: Boehringer Ingelheim and Eli Lilly and Company.

Published
2022

14. NT-proBNP and stem cell factor plasma concentrations are independently associated with cardiovascular outcomes in end-stage renal disease hemodialysis patients

Author

P Rossignol, K Duarte, E Bresso, Åsberg A, M D Devignes, N Eriksson, N Girerd, R Glerup, A G Jardine, H Holdaas, Z Lamiral, C Leroy, Z Massy, W März, B Krämer, P H Wu, R Schmieder, I Soveri, J H Christensen, M Svensson, F Zannad, B Fellström, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Hôpital Princesse Grace [Monaco], Computational Algorithms for Protein Structures and Interactions (CAPSID), Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Department of Complex Systems, Artificial Intelligence & Robotics (LORIA - AIS), Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Department of Transplantation Medicine Oslo University Hospital-Rikshospitalet, University of Oslo (UiO), UCR Uppsala Clinical Research Center, Uppsala Science Park, Department of Nephrology, Aalborg University Hospital, British Heart Foundation Glasgow Cardiovascular Research Centre (BHF GCRC), University of Glasgow-NHS Greater Glasgow and Clyde, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service Néphrologie/Dialyse [AP-HP Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], University Hospital Mannheim | Universitätsmedizin Mannheim, Medical University of Graz, Uppsala Universitet [Uppsala], Kaohsiung Medical University Hospital [Kaohsiung, Taïwan], Kaohsiung Medical University [Kaohsiung, Taïwan] (KMU), University Hospital Erlangen = Uniklinikum Erlangen, Aarhus University Hospital, The original AURORA trial was sponsored by Astra ZENECA. The present analyses and statistical work presented in this paper were jointly sponsored by the involved universities (R.S., A.J., H.H., B.F., W.M., and B.K.K.), ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), and ANR-15-IDEX-0004,LUE,Isite LUE(2015)

Subjects
[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, NT-proBNP, Urologi och njurmedicin, Urology and Nephrology, Cardiovascular, Prognosis, Chronic hemodialysis, Cardiovascula, Stem cell factor
Abstract

AimsEnd-stage renal disease (ESRD) treated by chronic hemodialysis (HD) is associated with poor cardiovascular (CV) outcomes, with no available evidence-based therapeutics. A multiplexed proteomic approach may identify new pathophysiological pathways associated with CV outcomes, potentially actionable for precision medicine.Methods and resultsThe AURORA trial was an international, multicentre, randomized, double-blind trial involving 2776 patients undergoing maintenance HD. Rosuvastatin vs. placebo had no significant effect on the composite primary endpoint of death from CV causes, nonfatal myocardial infarction or nonfatal stroke. We first compared CV risk-matched cases and controls (n = 410) to identify novel biomarkers using a multiplex proximity extension immunoassay (276 proteomic biomarkers assessed with OlinkTM). We replicated our findings in 200 unmatched cases and 200 controls. External validation was conducted from a multicentre real-life Danish cohort [Aarhus-Aalborg (AA), n = 331 patients] in which 92 OlinkTM biomarkers were assessed. In AURORA, only N-terminal pro-brain natriuretic peptide (NT-proBNP, positive association) and stem cell factor (SCF) (negative association) were found consistently associated with the trial's primary outcome across exploration and replication phases, independently from the baseline characteristics. Stem cell factor displayed a lower added predictive ability compared with NT-ProBNP. In the AA cohort, in multivariable analyses, BNP was found significantly associated with major CV events, while higher SCF was associated with less frequent CV deaths.ConclusionsOur findings suggest that NT-proBNP and SCF may help identify ESRD patients with respectively high and low CV risk, beyond classical clinical predictors and also point at novel pathways for prevention and treatment.

Published
2022

18. EMPEROR-Reduced : impact de l’empagliflozine sur les évènements cliniques chez les patients insuffisants cardiaques atteints de maladie rénale chronique

Author

N. Girerd, D. Ittah, and Comité de l’essai Emperor-Reduced

Subjects
Nephrology
Abstract

Introduction Dans EMPEROR-Reduced, etude realisee en insuffisance cardiaque a fraction d’ejection reduite (ICFER), avec ou sans diabete, l’empagliflozine reduisait le risque de deces cardiovasculaire et d’hospitalisation pour insuffisance cardiaque (IC) et ralentissait le declin de fonction renale. Description Nous avons explore l’effet de l’empagliflozine sur les criteres de jugement cardiovasculaires et renaux, en fonction du niveau d’atteinte renale. Methodes Au total, 3730 patients ont ete randomises, parmi lesquels 1978 (53 %) presentaient une maladie renale chronique (MRC) (DFGe 300 mg/g). Les criteres de jugement cles etaient : – un critere composite constitue du deces cardiovasculaire et de d’hospitalisation pour IC ; – le nombre total d’hospitalisations pour IC ; – la pente du DFGe ; cette derniere etait etayee par un critere de jugement renal composite predefini (declin important et durable du DFGe, dialyse chronique ou greffe). Le suivi median etait de 16 mois. Resultats Les patients avec IRC ont presente un taux plus eleve d’evenements CV et renaux. L’empagliflozine a reduit le risque de deces cardiovasculaire et d’hospitalisation pour IC de 25 % (p Fig. 1 ), notamment chez les patients ayant un DFGe compris entre 20 et 30 mL/min/1,73 m2. L’empagliflozine a ralenti significativement la perte annuelle de DFGe et a ete bien toleree quel que soit le niveau initial de fonction renale. Conclusion Chez les patients avec ICFER, l’empagliflozine reduit les evenements graves lies a l’IC et les evenements renaux, et ralenti le declin de la fonction renale independamment de la presence ou de l’absence de MRC.

Published
2021

19. P6392Left ventricular ejection fraction and adjudicated, cause-specific hospitalizations after myocardial infarction complicated by heart failure or left ventricular dysfunction

Author

Stefan Agewall, T. S. Hall, N. Girerd, F. Zannad, Dan Atar, Kevin Duarte, T. G. Von Lueder, Tahar Chouihed, Kenneth Dickstein, and Patrick Rossignol

Subjects
medicine.medical_specialty, Ventricular Ejection Fraction, business.industry, Internal medicine, Heart failure, Cardiology, Medicine, Myocardial infarction, Cardiology and Cardiovascular Medicine, business, medicine.disease, Cause specific
Published
2018

20. P4392Heart rate prediction of outcome in heart failure following myocardial infarction depend on heart rhythm status

Author

Zohra Lamiral, T A Von Lueder, Jean-Loup Machu, N. Girerd, Patrick Rossignol, F. Zannad, L. Tjessum, Dan Atar, Stefan Agewall, and John Kjekshus

Subjects
medicine.medical_specialty, business.industry, 030204 cardiovascular system & hematology, medicine.disease, Outcome (game theory), Heart Rhythm, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Heart failure, Cardiology, medicine, 030212 general & internal medicine, Myocardial infarction, Cardiology and Cardiovascular Medicine, business
Published
2017

21. [Evaluation of cardiac MRI in the follow up assessment of patients with pulmonary arterial hypertension]

Author

A, Chaouat, A, Cherifi, O, Sitbon, N, Girerd, M, Zysman, M, Faure, D, Mandry, M, Mercy, A, Guillaumot, R, Fay, P-Y, Marie, and F, Chabot

Subjects
Adult, Male, Cardiac Catheterization, Adolescent, Hypertension, Pulmonary, Hemodynamic Monitoring, Heart, Middle Aged, Prognosis, Magnetic Resonance Imaging, Sensitivity and Specificity, Young Adult, Predictive Value of Tests, Humans, Female, Aged, Follow-Up Studies, Retrospective Studies
Abstract

Haemodynamic follow up in pulmonary arterial hypertension (PAH) is currently based on right heart catheterisation (RHC). The primary objective of the EVITA study is to compare the use of cardiac magnetic resonance imaging (cMRI) with RHC in the identification of an unfavourable hemodynamic status. The secondary objectives are to determine the role of cMRI in the follow up process. Patients will undergo at diagnosis and at follow up visits both RHC and cMRI. Patients will be followed and treated according to the current guidelines. The primary endpoint will be an unfavourable haemodynamic status defined by cardiac index2.5L/min/m

Published
2017

22. Construction et évaluation d’un substitut de l’indice fonctionnel ECOG (PS), mesure de l’état de santé général du patient au diagnostic du cancer du sein métastatique

Author

I Piot, Geneviève Perrocheau, Anne Jaffre, N. Girerd-Chambaz, Etienne Brain, Simone Mathoulin-Pélissier, M. Robain, D. Pérol, Loïc Campion, B. Asselain, O. Payen, V. Diéras, and C. Courtinard

Subjects
Epidemiology, Public Health, Environmental and Occupational Health
Abstract

Introduction En oncologie, l’indice fonctionnel ECOG (PS), echelle de mesure de l’etat de sante general des patients, est un facteur pronostique systematiquement pris en compte dans les essais cliniques. Dans la pratique medicale courante, le PS est utilise par le medecin pour adapter la strategie therapeutique mais non systematiquement documente dans le dossier medical du patient. Le PS ne pouvant etre reporte retroactivement, la construction d’un substitut du PS permettrait de prendre en compte ce facteur dans les analyses sur donnees longitudinales retrospectives en vie reelle. L’objectif de ce travail etait de construire un substitut du PS a partir d’informations disponibles (âge, comorbidites, constantes biologiques) et decrire la performance du modele de prediction. Methodes A partir de la plateforme epidemio-strategie et medico-economique (ESME) des CLCCs sur le cancer du sein metastatique (CSM), les donnees de 865 patients traites dans quatre centres pour leur maladie metastatique a partir de 2014 ont ete extraites. Un recueil retrospectif a ete a ete organise concernant les comorbidites de Charslon et des valeurs biologiques (hematologie et biochimie). Un modele de regression logistique a ete utilise pour predire le substitut du PS. Les variables utilisees pour predire le PS etaient : l’âge, le statut menopausique, le score de Charslon, les transaminases, la bilirubine, la creatinine, les LDH, l’hemoglobine et les lymphocytes. Le PS a ete evalue selon deux seuils (PS > 0 et PS > 1). La performance du modele a ete utilisee par la methode de l’aire sous la courbe de ROC. Resultats Une mesure du PS au diagnostic de la maladie metastatique etait documentee chez 28 % seulement des 865 patients identifies. Les 619 patients sans mesure du PS ont ete exclus de l’analyse (316 patients sans aucune mesure du PS disponible dans le dossier medical et 303 patients avec une mesure du PS non disponible au diagnostic metastatique). Les patients exclus etaient un peu plus âges (63,2 versus 60,0, p 0 pour lequel l’âge (OR = 1,01 ; IC95 % [1,02–1,09]) et la bilirubine (OR = 8,01 ; [1,31–50,40]) etaient significativement associes. Les memes variables ont ete suggerees a partir d’une cohorte de validation externe comprenant 164 patients malgre une performance peu informative (AUC Conclusion Ce premier travail sur la prediction d’un substitut du PS suggere l’âge et un marqueur hepatique comme variables candidates pour integrer le modele de prediction. Malgre son utilisation courante dans le domaine de la prediction, le score de Charlson n’a pas ete retenu dans le modele final. L’evaluation de la performance du modele etait moyennement informative. Une etude prospective avec un effectif plus important et au diagnostic du cancer du sein metastatique, une mesure systematique du PS, l’administration d’un questionnaire de qualite de vie et la collecte de constantes biologiques permettrait de confirmer ces resultats.

Published
2018

23. Metabolic syndrome, abdominal obesity and hyperuricemia in schizophrenia: Results from the FACE-SZ cohort

Author

O. Godin, M. Leboyer, A. Gaman, B. Aouizerate, F. Berna, L. Brunel, D. Capdevielle, I. Chereau, J.M. Dorey, C. Dubertret, J. Dubreucq, C. Faget, F. Gabayet, Y. Le Strat, P.M. Llorca, D. Misdrahi, R. Rey, R. Richieri, C. Passerieux, A. Schandrin, F. Schürhoff, M. Urbach, P. Vidalhet, N. Girerd, G. Fond, O. Blanc, E. Bulzacka, I. Chereau-Boudet, G. Chesnoy-Servanin, J.M. Danion, T. D'Amato, A. Deloge, C. Delorme, H. Denizot, M. Depradier, C. Fluttaz, S. Fonteneau, E. Giraud-Baro, M.C. Hardy-Bayle, D. Lacelle, C. Lançon, H. Laouamri, T. Le Gloahec, E. Metairie, I. Offerlin-Meyer, P. Peri, S. Pires, C. Portalier, C. Roman, M. Sebilleau, A. Tessier, A.M. Tronche, F. Vaillant, A. Vehier, P. Vidailhet, E. Vilà, H. Yazbek, A. Zinetti-Bertschy, Fondation FondaMental [Créteil], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Psychiatrie et Neurologie personnalisées [AP-HP Hôpital Henri-Mondor] (DHU PePsy), Hôpital Henri Mondor, Centre Hospitalier Charles PERRENS, Physiopathologie du système nerveux central - Institut François Magendie, Université Bordeaux Segalen - Bordeaux 2-IFR8-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuropsychologie Cognitive et Physiopathologie de la Schizophrénie (NCPS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Hôpital de la Colombière, Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre Hospitalier le Vinatier [Bron], Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Référent de Réhabilitation Psychosociale [CH Alpes Isère], Centre Hospitalier Alpes Isère, Département Universitaire de Psychiatrie - [Hôpital Sainte Marguerite - APHM] (Hôpitaux Sud), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud )-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Hôpital Charles Perrens, Centre Hospitalier de Versailles André Mignot (CHV), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), AP-HP Hôpital Henri Mondor (Créteil), Neuropsychologie Cognitive et Physiopathologie de la Schizophrénie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Hôpital Civil de Strasbourg, Neuropsychiatrie : recherche épidémiologique et clinique, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Hopital Louis Mourier - AP-HP [Colombes], Pôle de Psychiatrie Universitaire Solaris, Marseille, Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Centre Hospitalier de Versailles (CHV), UFR des Sciences de la Santé Simone Veil, Centre d'investigation clinique plurithématique Pierre Drouin (CIC-P), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre de Psychiatrie et Neurosciences (U894), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier Charles Perrens [Bordeaux], and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)

Subjects
Male, MESH: Psychiatric Status Rating Scales, MESH: Chi-Square Distribution, Blood Pressure, MESH: Metabolic Diseases, Comorbidity, MESH: Lipoproteins, HDL, Body Mass Index, Cohort Studies, 0302 clinical medicine, Prevalence, Hyperuricemia, MESH: Cohort Studies, Abdominal obesity, Anthropometry, MESH: Blood Pressure, MESH: Hyperuricemia, Metabolic syndrome, 3. Good health, Psychiatry and Mental health, MESH: Young Adult, Obesity, Abdominal, Cohort, Female, France, medicine.symptom, Lipoproteins, HDL, Adult, medicine.medical_specialty, MESH: Obesity, Abdominal, MESH: Body Mass Index, Young Adult, 03 medical and health sciences, Metabolic Diseases, MESH: Anthropometry, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, Risk factor, Biological Psychiatry, MESH: Prevalence, Psychiatric Status Rating Scales, Chi-Square Distribution, MESH: Humans, business.industry, MESH: Adult, medicine.disease, MESH: Male, MESH: Schizophrenia, 030227 psychiatry, MESH: France, Endocrinology, Schizophrenia, business, Body mass index, MESH: Female, 030217 neurology & neurosurgery, Dyslipidemia
Abstract

Objective Abdominal obesity was suggested to be a better predictor than Metabolic Syndrome (MetS) for cardiovascular mortality, however this is has not been extensively studied in schizophrenia. Hyperuricemia (HU) was also suggested to be both an independent risk factor for greater somatic comorbidity and a global metabolic stress marker in patients with schizophrenia. The aim of this study was to estimate the prevalence of MetS, abdominal obesity and HU, to examine the association between metabolic parameters with HU in a cohort of French patients with schizophrenia or schizo-affective disorder (SZ), and to estimate the prevalence rates of treatment of cardio-vascular risk factors. Method 240 SZ patients (age = 31.4 years, male gender 74.3%) were systematically included. Metabolic syndrome was defined according to the International Diabetes Federation and HU if serum uric acid level was above 360 μmol/L. Results MetS, abdominal obesity and HU were found respectively in 24.2%, 21.3% and 19.6% of patients. In terms of risk factors, multiple logistic regression showed that after taking into account the potential confounders, the risk for HU was higher in males (OR = 5.9, IC95 [1.7–21.4]) and in subjects with high waist circumference (OR = 3.1, IC95 [1.1–8.3]) or hypertriglyceridemia (OR = 4.9, IC95 [1.9–13]). No association with hypertension, low HDL cholesterol or high fasting glucose was observed. Only 10% of patients with hypertension received a specific treatment, 18% for high fasting glucose and 8% for dyslipidemia. Conclusions The prevalence of MetS, abdominal obesity and hyperuricemia is elevated in French patients with schizophrenia, all of which are considerably under-diagnosed and undertreated. HU is strongly associated with abdominal obesity but not with psychiatric symptomatology.

Published
2015

24. INCIDENCE, PREDICTORS, AND IMPACT OF BIOPROSTHETIC VALVE HEMODYNAMIC DETERIORATION FOLLOWING AORTIC VALVE REPLACEMENT

Author

Bobby Yanagawa, Haïfa Mahjoub, Dimitri Kalavrouziotis, Subodh Verma, Siamak Mohammadi, Marie-Annick Clavel, François Dagenais, P. Pibarot, N. Girerd, Peter Jüni, Erwan Salaun, and Pierre Voisine

Subjects
Bioprosthetic valve, medicine.medical_specialty, Aortic valve replacement, business.industry, Internal medicine, Incidence (epidemiology), Cardiology, medicine, Hemodynamics, Cardiology and Cardiovascular Medicine, business, medicine.disease
Published
2017

25. CMS physics technical design report, volume II: Physics performance

Author

Bayatian, G.L. Chatrchyan, S. Hmayakyan, G. Sirunyan, A.M. Adam, W. Bergauer, T. Dragicevic, M. Erö, J. Friedl, M. Fruehwirth, R. Ghete, V. Glaser, P. Hrubec, J. Jeitler, M. Krammer, M. Magrans, I. Mikulec, I. Mitaroff, W. Noebauer, T. Pernicka, M. Porth, P. Rohringer, H. Strauss, J. Taurok, A. Waltenberger, W. Walzel, G. Widl, E. Wulz, C.-E. Fedorov, A. Korzhik, M. Missevitch, O. Zuyeuski, R. Chekhovsky, V. Dvornikov, O. Emeliantchik, I. Litomin, A. Mossolov, V. Shumeiko, N. Solin, A. Stefanovitch, R. Suarez Gonzalez, J. Tikhonov, A. Petrov, V. D'Hondt, J. De Weirdt, S. Goorens, R. Heyninck, J. Lowette, S. Tavernier, S. Van Doninck, W. Van Lancker, L. Bouhali, O. Clerbaux, B. De Lentdecker, G. Dewulf, J.P. Mahmoud, T. Marage, P.E. Neukermans, L. Sundararajan, V. Vander Velde, C. Vanlaer, P. Wickens, J. Assouak, S. Bonnet, J.L. Bruno, G. Caudron, J. De Callatay, B. De Favereau De Jeneret, J. De Visscher, S. Delaere, C. Demin, P. Favart, D. Feltrin, E. Forton, E. Grégoire, G. Kalinin, S. Kcira, D. Keutgen, T. Leibenguth, G. Lemaitre, V. Liu, Y. Michotte, D. Militaru, O. Ninane, A. Ovyn, S. Pierzchala, T. Piotrzkowski, K. Roberfroid, V. Rouby, X. Teyssier, D. Van Der Aa, O. Vander Donckt, M. Daubie, E. Herquet, P. Mollet, A. Romeyer, A. Beaumont, W. Cardaci, M. De Langhe, E. De Wolf, E.A. Rurua, L. Souza, M.H.G. Oguri, V. Santoro, A. Sznajder, A. Vaz, M. Gregores, E.M. Novaes, S.F. Anguelov, T. Antchev, G. Atanasov, I. Damgov, J. Darmenov, N. Dimitrov, L. Genchev, V. Iaydjiev, P. Panev, B. Piperov, S. Stoykova, S. Sultanov, G. Vankov, I. Dimitrov, A. Kozhuharov, V. Litov, L. Makariev, M. Marinov, A. Marinova, E. Markov, S. Mateev, M. Pavlov, B. Petkov, P. Sabev, C. Stoynev, S. Toteva, Z. Verguilov, V. Chen, G.M. Chen, H.S. He, K.L. Jiang, C.H. Li, W.G. Liu, H.M. Meng, X. Shen, X.Y. Sun, H.S. Yang, M. Zhao, W.R. Zhuang, H.L. Ban, Y. Cai, J. Liu, S. Qian, S.J. Yang, Z.C. Ye, Y.L. Ying, J. Wu, J. Zhang, Z.P. Godinovic, N. Puljak, I. Soric, I. Antunovic, Z. Dzelalija, M. Marasovic, K. Brigljevic, V. Ferencek, D. Kadija, K. Morovic, S. Planinic, M. Nicolaou, C. Papadakis, A. Razis, P.A. Tsiakkouri, D. Hektor, A. Kadastik, M. Kannike, K. Lippmaa, E. Müntel, M. Raidal, M. Aarnio, P.A. Czellar, S. Haeggstroem, E. Heikkinen, A. Härkönen, J. Karimäki, V. Kinnunen, R. Lampén, T. Lassila-Perini, K. Lehti, S. Lindén, T. Luukka, P.R. Michal, S. Mäenpää, T. Nysten, J. Stettler, M. Tuominen, E. Tuominiemi, J. Wendland, L. Tuuva, T. Guillaud, J.P. Nedelec, P. Sillou, D. Anfreville, M. Beauceron, S. Bougamont, E. Bredy, P. Chipaux, R. Dejardin, M. Denegri, D. Descamps, J. Fabbro, B. Faure, J.L. Ganjour, S. Gentit, F.X. Givernaud, A. Gras, P. Hamel De Monchenault, G. Jarry, P. Kircher, F. Lemaire, M.C. Levesy, B. Locci, E. Lottin I Mandjavidze, J.P. Mur, M. Pasquetto, E. Payn, A. Rander, J. Reymond, J.M. Rondeaux, F. Rosowsky, A. Sun, Z.H. Verrecchia, P. Baffioni, S. Beaudette, F. Bercher, M. Berthon, U. Bimbot, S. Bourotte, J. Busson, P. Cerutti, M. Chamont, D. Charlot, C. Collard, C. Decotigny, D. Delmeire, E. Dobrzynski, L. Gaillac, A.M. Geerebaert, Y. Gilly, J. Haguenauer, M. Karar, A. Mathieu, A. Milleret, G. Miné, P. Paganini, P. Romanteau, T. Semeniouk, I. Sirois, Y. Berst, J.D. Brom, J.M. Didierjean, F. Drouhin, F. Fontaine, J.C. Goerlach, U. Graehling, P. Gross, L. Houchu, L. Juillot, P. Lounis, A. Maazouzi, C. Mangeol, D. Olivetto, C. Todorov, T. Van Hove, P. Vintache, D. Ageron, M. Agram, J.L. Baulieu, G. Bedjidian, M. Blaha, J. Bonnevaux, A. Boudoul, G. Chabanat, E. Combaret, C. Contardo, D. Della Negra, R. Depasse, P. Dupasquier, T. El Mamouni, H. Estre, N. Fay, J. Gascon, S. Giraud, N. Girerd, C. Haroutunian, R. Ianigro, J.C. Ille, B. Lethuillier, M. Lumb, N. Mathez, H. Maurelli, G. Mirabito, L. Perries, S. Ravat, O. Kvatadze, R. Roinishvili, V. Adolphi, R. Brauer, R. Braunschweig, W. Esser, H. Feld, L. Heister, A. Karpinski, W. Klein, K. Kukulies, C. Olzem, J. Ostapchuk, A. Pandoulas, D. Pierschel, G. Raupach, F. Schael, S. Schwering, G. Thomas, M. Weber, M. Wittmer, B. Wlochal, M. Adolf, A. Biallass, P. Bontenackels, M. Erdmann, M. Fesefeldt, H. Hebbeker, T. Hermann, S. Hilgers, G. Hoepfner, K. Hof, C. Kappler, S. Kirsch, M. Lanske, D. Philipps, B. Reithler, H. Rommerskirchen, T. Sowa, M. Szczesny, H. Tonutti, M. Tsigenov, O. Beissel, F. Davids, M. Duda, M. Flügge, G. Franke, T. Giffels, M. Hermanns, T. Heydhausen, D. Kasselmann, S. Kaussen, G. Kress, T. Linn, A. Nowack, A. Poettgens, M. Pooth, O. Stahl, A. Tornier, D. Weber, M. Flossdorf, A. Hegner, B. Mnich, J. Rosemann, C. Flucke, G. Holm, U. Klanner, R. Pein, U. Schirm, N. Schleper, P. Steinbrück, G. Stoye, M. Van Staa, R. Wick, K. Blüm, P. Buege, V. De Boer, W. Dirkes, G. Fahrer, M. Feindt, M. Felzmann, U. Fernandez Menendez, J. Frey, M. Furgeri, A. Hartmann, F. Heier, S. Jung, C. Ledermann, B. Müller, Th. Niegel, M. Oehler, A. Ortega Gomez, T. Piasecki, C. Quast, G. Rabbertz, K. Saout, C. Scheurer, A. Schieferdecker, D. Schmidt, A. Simonis, H.J. Theel, A. Vest, A. Weiler, T. Weiser, C. Weng, J. Zhukov, V. Karapostoli, G. Katsas, P. Kreuzer, P. Panagiotou, A. Papadimitropoulos, C. Anagnostou, G. Barone, M. Geralis, T. Kalfas, C. Koimas, A. Kyriakis, A. Kyriazopoulou, S. Loukas, D. Markou, A. Markou, C. Mavrommatis, C. Theofilatos, K. Vermisoglou, G. Zachariadou, A. Aslanoglou, X. Evangelou, I. Kokkas, P. Manthos, N. Papadopoulos, I. Sidiropoulos, G. Triantis, F.A. Bencze, G. Boldizsar, L. Hajdu, C. Horvath, D. Laszlo, A. Odor, G. Sikler, F. Toth, N. Vesztergombi, G. Zalan, P. Molnar, J. Beni, N. Kapusi, A. Marian, G. Raics, P. Szabo, Z. Szillasi, Z. Zilizi, G. Bawa, H.S. Beri, S.B. Bhandari, V. Bhatnagar, V. Kaur, M. Kaur, R. Kohli, J.M. Kumar, A. Singh, J.B. Bhardwaj, A. Bhattacharya, S. Chatterji, S. Chauhan, S. Choudhary, B.C. Gupta, P. Jha, M. Ranjan, K. Shivpuri, R.K. Srivastava, A.K. Borkar, S. Dixit, M. Ghodgaonkar, M. Kataria, S.K. Lalwani, S.K. Mishra, V. Mohanty, A.K. Topkar, A. Aziz, T. Banerjee, S. Bose, S. Cheere, N. Chendvankar, S. Deshpande, P.V. Guchait, M. Gurtu, A. Maity, M. Majumder, G. Mazumdar, K. Nayak, A. Patil, M.R. Sharma, S. Sudhakar, K. Tonwar, S.C. Acharya, B.S. Banerjee, S. Bheesette, S. Dugad, S. Kalmani, S.D. Lakkireddi, V.R. Mondal, N.K. Panyam, N. Verma, P. Arabgol, M. Arfaei, H. Hashemi, M. Mohammadi, M. Mohammadi Najafabadi, M. Moshaii, A. Paktinat Mehdiabadi, S. Grunewald, M. Abbrescia, M. Barbone, L. Colaleo, A. Creanza, D. De Filippis, N. De Palma, M. Donvito, G. Fiore, L. Giordano, D. Iaselli, G. Loddo, F. Maggi, G. Maggi, M. Manna, N. Marangelli, B. Mennea, M.S. My, S. Natali, S. Nuzzo, S. Pugliese, G. Radicci, V. Ranieri, A. Romano, F. Selvaggi, G. Silvestris, L. Tempesta, P. Trentadue, R. Zito, G. Abbiendi, G. Bacchi, W. Benvenuti, A. Bonacorsi, D. Braibant-Giacomelli, S. Capiluppi, P. Cavallo, F.R. Ciocca, C. Codispoti, G. D'Antone, I. Dallavalle, G.M. Fabbri, F. Fanfani, A. Giacomelli, P. Grandi, C. Guerzoni, M. Guiducci, L. Marcellini, S. Masetti, G. Montanari, A. Navarria, F. Odorici, F. Perrotta, A. Rossi, A. Rovelli, T. Siroli, G. Travaglini, R. Albergo, S. Chiorboli, M. Costa, S. Galanti, M. Gatto Rotondo, G. Noto, F. Potenza, R. Russo, G. Tricomi, A. Tuve, C. Bocci, A. Ciraolo, G. Ciulli, V. Civinini, C. D'Alessandro, R. Focardi, E. Genta, C. Lenzi, P. Macchiolo, A. Magini, N. Manolescu, F. Marchettini, C. Masetti, L. Mersi, S. Meschini, M. Paoletti, S. Parrini, G. Ranieri, R. Sani, M. Fabbricatore, P. Farinon, S. Greco, M. Cattaneo, G. De Min, A. Dominoni, M. Farina, F.M. Ferri, F. Ghezzi, A. Govoni, P. Leporini, R. Magni, S. Malberti, M. Malvezzi, S. Marelli, S. Menasce, D. Moroni, L. Negri, P. Paganoni, M. Pedrini, D. Pullia, A. Ragazzi, S. Redaelli, N. Rovelli, C. Rovere, M. Sala, L. Sala, S. Salerno, R. Tabarelli De Fatis, T. Vigano', S. Comunale, G. Fabozzi, F. Lomidze, D. Mele, S. Paolucci, P. Piccolo, D. Polese, G. Sciacca, C. Azzi, P. Bacchetta, N. Bellato, M. Benettoni, M. Bisello, D. Borsato, E. Candelori, A. Checchia, P. Conti, E. De Mattia, M. Dorigo, T. Drollinger, V. Fanzago, F. Gasparini, F. Gasparini, U. Giarin, M. Giubilato, P. Gonella, F. Kaminskiy, A. Karaevskii, S. Khomenkov, V. Lacaprara, S. Lippi, I. Loreti, M. Lytovchenko, O. Mazzucato, M. Meneguzzo, A.T. Michelotto, M. Montecassiano, F. Nigro, M. Passaseo, M. Pegoraro, M. Rampazzo, G. Ronchese, P. Torassa, E. Ventura, S. Zanetti, M. Zotto, P. Zumerle, G. Belli, G. Berzano, U. De Vecchi, C. Guida, R. Necchi, M.M. Ratti, S.P. Riccardi, C. Sani, G. Torre, P. Vitulo, P. Ambroglini, F. Babucci, E. Benedetti, D. Biasini, M. Bilei, G.M. Caponeri, B. Checcucci, B. Fanò, L. Lariccia, P. Mantovani, G. Passeri, D. Pioppi, M. Placidi, P. Postolache, V. Ricci, D. Santocchia, A. Servoli, L. Spiga, D. Azzurri, P. Bagliesi, G. Basti, A. Benucci, L. Bernardini, J. Boccali, T. Borrello, L. Bosi, F. Calzolari, F. Castaldi, R. Cerri, C. Cucoanes, A.S. D'Alfonso, M. Dell'Orso, R. Dutta, S. Foà, L. Gennai, S. Giammanco, A. Giassi, A. 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Wang, S. Anderson, E.W. Atramentov, O. Hauptman, J.M. Lamsa, J. Barnett, B.A. Blumenfeld, B. Chien, C.Y. Kim, D.W. Maksimovic, P. Spangler, S. Swartz, M. Baringer, P. Bean, A. Coppage, D. Grachov, O. Kim, E.J. Murray, M. Bandurin, D. Bolton, T. Khanov, A. Maravin, Y. Onoprienko, D. Rizatdinova, F. Sidwell, R. Stanton, N. Von Toerne, E. Baden, D. Bard, R. Eno, S.C. Grassi, T. Hadley, N.J. Kellogg, R.G. Kunori, S. Ratnikov, F. Skuja, A. Arcidiacono, R. Ballintijn, M. Bauer, G. Harris, P. Kravchenko, I. Loizides, C. Nahn, S. Paus, C. Pavlon, S. Roland, C. Roland, G. Sumorok, K. Vaurynovich, S. Veres, G. Wyslouch, B. Bailleux, D. Corum, S. Cushman, P. De Benedetti, A. Dolgopolov, A. Egeland, R. Franzoni, G. Gilbert, W.J. Grahl, J. Haupt, J. Kubota, Y. Mans, J. Pearson, N. Rusack, R. Singovsky, A. Cremaldi, L.M. Godang, R. Kroeger, R. Sanders, D.A. Summers, D. Bloom, K. Claes, D.R. Dominguez, A. Eads, M. Lundstedt, C. Malik, S. Snow, G.R. Sobol, A. Iashvili, I. Kharchilava, A. Alverson, G. Barberis, E. Boeriu, O. Eulisse, G. Musienko, Y. Muzaffar, S. Osborne, I. Reucroft, S. Swain, J. Taylor, L. Tuura, L. Wood, D. Gobbi, B. Kubantsev, M. Schellman, H. Schmitt, M. Spencer, E. Velasco, M. Baumbaugh, B. Cason, N.M. Hildreth, M. Karmgard, D.J. Marinelli, N. Ruchti, R. Warchol, J. Wayne, M. Bylsma, B. Durkin, L.S. Gilmore, J. Gu, J. Herman, D. Killewald, P. Knobbe, K. Ling, T.Y. Elmer, P. Marlow, D. Piroué, P. Stickland, D. Tully, C. Wildish, T. Wynhoff, S. Xie, Z. Apresyan, A. Arndt, K. Banicz, K. Barnes, V.E. Bolla, G. Bortoletto, D. Bujak, A. Garfinkel, A.F. Gonzalez Lopez, O. Gutay, L. Ippolito, N. Kozhevnikov, Y. Laasanen, A.T. Liu, C. Maroussov, V. Merkel, P. Miller, D.H. Miyamoto, J. Neumeister, N. Rott, C. Roy, A. Sedov, A. Shipsey, I. Parashar, N. Eppley, G. Lee, S.J. Liu, J. Matveev, M. Nussbaum, T. Padley, B.P. Roberts, J. Tumanov, A. Yepes, P. Bodek, A. Budd, H. Chung, Y.S. De Barbaro, P. Demina, R. Eusebi, R. Ginther, G. Gotra, Y. Hocker, A. Husemann, U. Korjenevski, S. Sakumoto, W. Slattery, P. Tipton, P. Zielinski, M. Bartz, E. Doroshenko, J. Halkiadakis, E. Jacques, P.F. Kalelkar, M.S. Khits, D. Lath, A. Macpherson, A. Perera, L. Plano, R. Rose, K. Schnetzer, S. Somalwar, S. Stone, R. Thomson, G. Watts, T.L. Akchurin, N. Carrell, K.W. Gumus, K. Jeong, C. Kim, H. Papadimitriou, V. Sill, A. Spezziga, M. Washington, E. Wigmans, R. Zhang, L. Bapty, T. Engh, D. Johns, W. Keskinpala, T. Luiggi Lopez, E. Neema, S. Nordstrom, S. Pathak, S. Sheldon, P. Vaandering, E.W. Webster, M. Arenton, M.W. Conetti, S. Cox, B. Hirosky, R. Imlay, R. Ledovskoy, A. Phillips Ii, D. Powell, H. Ronquest, M. Smith, D. Baek, Y.W. Bellinger, J.N. Bradley, D. Carlsmith, D. Crotty, I. Dasu, S. Feyzi, F. Gorski, T. Grothe, M. Hogg, W. Jaworski, M. Klabbers, P. Lanaro, A. Loveless, R. De Magrans Abril, M. Reeder, D. Smith, W.H. Wenman, D. Atoyan, G.S. Dhawan, S. Issakov, V. Neal, H. Poblaguev, A. Zeller, M.E. Yuldashev, B.S.

Subjects
High Energy Physics::Phenomenology, High Energy Physics::Experiment
Abstract

CMS is a general purpose experiment, designed to study the physics of pp collisions at 14 TeV at the Large Hadron Collider (LHC). It currently involves more than 2000 physicists from more than 150 institutes and 37 countries. The LHC will provide extraordinary opportunities for particle physics based on its unprecedented collision energy and luminosity when it begins operation in 2007. The principal aim of this report is to present the strategy of CMS to explore the rich physics programme offered by the LHC. This volume demonstrates the physics capability of the CMS experiment. The prime goals of CMS are to explore physics at the TeV scale and to study the mechanism of electroweak symmetry breaking - through the discovery of the Higgs particle or otherwise. To carry out this task, CMS must be prepared to search for new particles, such as the Higgs boson or supersymmetric partners of the Standard Model particles, from the start-up of the LHC since new physics at the TeV scale may manifest itself with modest data samples of the order of a few fb-1 or less. The analysis tools that have been developed are applied to study in great detail and with all the methodology of performing an analysis on CMS data specific benchmark processes upon which to gauge the performance of CMS. These processes cover several Higgs boson decay channels, the production and decay of new particles such as Z′ and supersymmetric particles, Bs production and processes in heavy ion collisions. The simulation of these benchmark processes includes subtle effects such as possible detector miscalibration and misalignment. Besides these benchmark processes, the physics reach of CMS is studied for a large number of signatures arising in the Standard Model and also in theories beyond the Standard Model for integrated luminosities ranging from 1 fb-1 to 30 fb-1. The Standard Model processes include QCD, B-physics, diffraction, detailed studies of the top quark properties, and electroweak physics topics such as the W and Z0 boson properties. The production and decay of the Higgs particle is studied for many observable decays, and the precision with which the Higgs boson properties can be derived is determined. About ten different supersymmetry benchmark points are analysed using full simulation. The CMS discovery reach is evaluated in the SUSY parameter space covering a large variety of decay signatures. Furthermore, the discovery reach for a plethora of alternative models for new physics is explored, notably extra dimensions, new vector boson high mass states, little Higgs models, technicolour and others. Methods to discriminate between models have been investigated. This report is organized as follows. Chapter 1, the Introduction, describes the context of this document. Chapters 2-6 describe examples of full analyses, with photons, electrons, muons, jets, missing E T, B-mesons and τ's, and for quarkonia in heavy ion collisions. Chapters 7-15 describe the physics reach for Standard Model processes, Higgs discovery and searches for new physics beyond the Standard Model. © 2007 IOP Publishing Ltd.

Published
2007

26. Clinical benefits of Eplerenone in patients with systolic NYHA II heart failure when initiated shortly after hospital discharge

Author

D.J. Van Veldhuisen, Timothy Collier, Stuart J. Pocock, N. Girerd, J. Vincent, Jjv McMurray, F. Zannad, Bertram Pitt, Karl Swedberg, and Henry Krum

Subjects
medicine.medical_specialty, Ejection fraction, business.industry, medicine.disease, Placebo, Eplerenone, Interquartile range, Internal medicine, Heart failure, Relative risk, medicine, Cardiology, Systole, Cardiology and Cardiovascular Medicine, business, Survival analysis, medicine.drug
Abstract

Purpose: Cardiovascular hospitalization (CVH) in patients with heart failure (HF) is associated with a high post-discharge rate of re-admission and CV death. Eplerenone might be effective in reducing the incidence of these adverse clinical outcomes. Methods: The EMPHASIS-HF trial compared eplerenone to placebo added to standard therapy in 2737 patients with NYHA class II HF and LV ejection fraction

Published
2013

27. Examining the clinical role and educational preparation of heart failure nurses across Europe. A survey of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) and the Association of Cardiovascular Nursing and Allied Professions (ACNAP) of the ESC.

Author

Hill L, Girerd N, Castiello T, Jaarsma T, Metra M, Rosano G, Savage P, Schuuring MJ, Simpson M, Uchmanowicz I, Volterrani M, Williams R, Lambrinou E, and Hage C

Abstract

Aims: To describe the clinical practice and educational preparation of heart failure (HF) nurses across Europe and determine the key differences between countries., Methods and Results: A survey tool was developed, in English, by the Heart Failure Association Patient Care committee of the European Society of Cardiology (ESC). It was translated into eight languages, before electronically disseminated by nurse ambassadors, presidents of HF national societies and through social media. A total of 837 nurses involved in the daily care of patients with HF from 15 countries completed the survey. Most nurses, 78% (n = 395) worked within a hospital outpatient setting, and 51% (n = 431) had access to a specialized HF multidisciplinary team. Nurses performed a range of activities including patient education to promote self-care, virtual and in-person symptom monitoring. A third had more than 5-year experience in cardiac care and 22% (n = 182) prescribed HF medications. There was a significant correlation between HF nurses that prescribed HF medications and access to a specialist multidisciplinary team (p = 0.04). A small number of nurses, mainly from Belgium, supported invasive monitoring (n = 68, 8%) with 14% (n = 120) of mostly Danish nurses supporting exercise programmes. The majority of nurses surveyed were committed to further academic professional development, with 41% (n = 343) having completed a HF course., Conclusion: The role of the HF nurse varies across Europe, however involvement in patient education, symptom monitoring and follow-up remain core to their practice. In specific activities including the prescribing of HF medications and involvement in invasive monitoring, practice has advanced with collaboration in the multidisciplinary team. Consequently, harmonization of education, training and career pathways are required to standardize HF care aligned with expert guidelines across Europe., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Published
2024
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28. Prognostic value of ventricular arrhythmia in early post-infarction left ventricular dysfunction: the French nationwide WICD-MI study.

Author

Echivard M, Sellal JM, Ziliox C, Marijon E, Bordachar P, Ploux S, Benali K, Marquié C, Docq C, Klug D, Eschalier R, Maille B, Deharo JC, Babuty D, Genet T, Gandjbakhch E, Da Costa A, Piot O, Minois D, Gourraud JB, Mondoly P, Maury P, Boveda S, Pasquié JL, Martins R, Leclercq C, Guenancia C, Laurent G, Becker M, Bertrand J, Chevalier P, Manenti V, Kubala M, Defaye P, Jacon P, Desbiolles A, Badoz M, Jesel L, Lellouche N, Milliez PU, Ollitrault P, Fareh S, Bercker M, Mansourati J, Guy-Moyat B, Chabert JP, Luconi N, Winum PF, Anselme F, Extramiana F, Delahaye C, Jourda F, Bizeau O, Nasarre M, Olivier A, Fromentin S, Villemin T, Levavasseur O, Hammache N, Magnin-Poull I, Blangy H, Sadoul N, Duarte K, Girerd N, and de Chillou C

Subjects
Humans, Male, Female, Retrospective Studies, Prognosis, Aged, Middle Aged, France epidemiology, Stroke Volume physiology, Tachycardia, Ventricular therapy, Tachycardia, Ventricular etiology, Tachycardia, Ventricular physiopathology, Ventricular Dysfunction, Left physiopathology, Ventricular Dysfunction, Left therapy, Ventricular Dysfunction, Left etiology, Myocardial Infarction complications, Myocardial Infarction mortality, Defibrillators, Implantable
Abstract

Background and Aims: Prophylactic implantable cardioverter-defibrillators (ICDs) are not recommended until left ventricular ejection fraction (LVEF) has been reassessed 40 to 90 days after an acute myocardial infarction. In the current therapeutic era, the prognosis of sustained ventricular arrhythmias (VAs) occurring during this early post-infarction phase (i.e. within 3 months of hospital discharge) has not yet been specifically evaluated in post-myocardial infarction patients with impaired LVEF. Such was the aim of this retrospective study., Methods: Data analysis was based on a nationwide registry of 1032 consecutive patients with LVEF ≤ 35% after acute myocardial infarction who were implanted with an ICD after being prescribed a wearable cardioverter-defibrillator (WCD) for a period of 3 months upon discharge from hospital after the index infarction., Results: ICDs were implanted either because a sustained VA occurred while on WCD (VA+/WCD, n = 72) or because LVEF remained ≤35% at the end of the early post-infarction phase (VA-/WCD, n = 960). The median follow-up was 30.9 months. Sustained VAs occurred within 1 year after ICD implantation in 22.2% and 3.5% of VA+/WCD and VA-/WCD patients, respectively (P < .0001). The adjusted multivariable analysis showed that sustained VAs while on WCD independently predicted recurrence of sustained VAs at 1 year (adjusted hazard ratio [HR] 6.91; 95% confidence interval [CI] 3.73-12.81; P < .0001) and at the end of follow-up (adjusted HR 3.86; 95% CI 2.37-6.30; P < .0001) as well as 1-year mortality (adjusted HR 2.86; 95% CI 1.28-6.39; P = .012)., Conclusions: In patients with LVEF ≤ 35%, sustained VA during the early post-infarction phase is predictive of recurrent sustained VAs and 1-year mortality., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Published
2024
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29. Effects of spironolactone on exercise blood pressure in patients at increased risk of developing heart failure: report from the HOMAGE trial.

Author

Wei FF, Pellicori P, Ferreira JP, González A, Mariottoni B, An DW, Verdonschot JAJ, Liu C, Ahmed FZ, Petutschnigg J, Rossignol P, Heymans S, Cuthbert J, Girerd N, Clark AL, Li Y, Nawrot TS, Díez J, Zannad F, Cleland JGF, and Staessen JA

Subjects
Humans, Male, Female, Middle Aged, Aged, Mineralocorticoid Receptor Antagonists therapeutic use, Treatment Outcome, Diuretics therapeutic use, Spironolactone therapeutic use, Heart Failure physiopathology, Heart Failure drug therapy, Blood Pressure drug effects, Quality of Life, Exercise
Abstract

None of the spironolactone trials in heart failure (HF) assessed the blood pressure (BP) responses to exercise, while conflicting results were reported for exercise capacity. In the HOMAGE trial, 527 patients at increased HF risk were randomized to usual treatment with or without spironolactone (25-50 mg/day). The current substudy included 113 controls and 114 patients assigned spironolactone, who all completed the incremental shuttle walk test at baseline and months 1 and 9. Quality of life (QoL) was assessed by EQ5D questionnaire. Between-group differences (spironolactone minus control [Δs]) were analyzed by repeated measures ANOVA with adjustment for baseline and, if appropriate, additionally for sex, age and body mass index. Δs in the pre-exercise systolic/diastolic BP were -8.00 mm Hg (95% CI, -11.6 to -4.43)/-0.85 mm Hg (-2.96 to 1.26) at month 1 and -9.58 mm Hg (-14.0 to -5.19)/-3.84 mm Hg (-6.22 to -1.47) at month 9. Δs in the post-exercise systolic/diastolic BP were -8.08 mm Hg (-14.2 to -2.01)/-2.07 mm Hg (-5.79 to 1.65) and -13.3 mm Hg (-19.9 to -6.75)/-4.62 mm Hg (-8.07 to -1.17), respectively. For completed shuttles, Δs at months 1 and 9 were 2.15 (-0.10 to 4.40) and 2.49 (-0.79 to 5.67), respectively. Δs in QoL were not significant. The correlations between the exercise-induced BP increases and the number of completed shuttles were similar in both groups. In conclusion, in patients at increased risk of developing HF, spironolactone reduced the pre- and post-exercise BP, but did not improve exercise capacity or QoL., (© 2024. The Author(s).)

Published
2024
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30. Proteomic biomarkers and pathway analysis for progression to heart failure in three epidemiological representative cohorts.

Author

Dieden A, Girerd N, Ottosson F, Molvin J, Pareek M, Melander O, Bachus E, Råstam L, Lindblad U, Daka B, Leósdóttir M, Nilsson PM, Olsen MH, Clark AL, Cleland JGF, Delles C, González A, Lamiral Z, Duarte K, Rossignol P, Zannad F, Gudmundsson P, Jujić A, and Magnusson M

Abstract

Aims: Biomarkers associated with asymptomatic ventricular dysfunction might improve risk stratification and identify pathways leading to heart failure (HF). We explored the association between proteomic biomarkers and left ventricular hypertrophy (LVH), diastolic dysfunction (DD) and incident HF in three population-based cohorts., Methods and Results: A chip was used to measure 92 protein biomarkers in blood samples from >1500 Malmö Preventive Project (MPP) participants, of whom 514 had LVH (34%), 462 had DD (32.4%) and, over a median follow-up of 13 (11-14) years, 130 developed HF (7.7%). Findings were confirmed in the STANISLAS (n > 1500, 238 participants with LVH, 76 with DD) and HOMAGE case-control (562 cases of incident HF, 871 controls) cohorts. In multivariable logistic or Cox regression analyses adjusted for age, sex and cardiovascular risk factors, N-terminal pro-B-type natriuretic peptide (NT-proBNP) was associated with LVH, DD and incident HF in all cohorts: MPP (LVH odds ratio [OR] [95% confidence interval] 1.48 [1.28-1.71]; DD OR 1.71 [1.53-1.92]; HF HR 1.98 [1.66-2.36]); STANISLAS (LVH OR 1.20 [1.02-1.41]; DD OR 1.46 [1.12-1.90]); HOMAGE (HF HR 1.85 [1.62-2.12]). Galectin-4, growth differentiation factor 15 and suppression of tumorigenicity-2 were associated with incident HF in MPP and HOMAGE. A pathway enrichment analysis suggested that inflammation and viral infection were related to incident HF., Conclusion: In conclusion, our study reinforces the role of NT-proBNP as a key biomarker for asymptomatic cardiac dysfunction and incident HF, consistent with its established use in clinical practice. This underscores the value of NT-proBNP for identifying patients at high risk for HF, and provides insights into pathways leading to HF and potential therapeutic targets., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Published
2024
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32. The assessment, interpretation and implementation of lung ultrasound examinations in Heart Failure: Current evidence and gaps in knowledge.

Author

Palazzuoli A, Beltrami M, Girerd N, Maw A, Ruocco G, and Platz E

Abstract

Lung ultrasound (LUS) is a simple, fast and non-invasive tool for pulmonary congestion assessment with higher accuracy for the detection of acute heart failure (HF) compared to clinical examination and chest radiography. The integrated assessment with other ultrasound and echocardiographic parameters can lead to a better systemic and pulmonary congestion characterization. Additionally, the combination of echocardiographic and pulmonary features can identify patients at higher risk for adverse outcomes, potentially facilitating both acute and chronic HF management and prognostic stratification. However, the optimal utilization of LUS needs to be better defined both in terms of imaging method and B-line thresholds which may differ based on the clinical scenario and, potentially, the HF phenotype. Despite the extensive potential role of LUS in a wide range of HF scenarios, clinicians may be unaware of the correct technique and exam interpretation. Specifically, the interpretation of LUS findings is influenced by several factors, such as imaging protocol, type of ultrasound transducer, patient positioning, and presence of concomitant pulmonary diseases. The aim of this review is to provide a practical overview of LUS in patients with known or suspected HF with the goal of providing a practical guide for clinicians and nurses in various clinical settings., Competing Interests: Declaration of competing interest NG was supported by Astrazeneca, Bayer, Boehringer, Echosens, Lilly, Novartis, Novonordisk, NP Medical. EP’s employer has received support from Novartis for consulting work, and she has consulted for scPharmaceuticals outside of the submitted work. She has received research support from the NIH (R01HL148439), the American Heart Association and AstraZeneca, and she serves on a clinical trial steering committee for Boehringer Ingelheim. The remaining authors declare they have no conflict of interest., (Copyright © 2024 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Published
2024
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33. 2023 SFMU/GICC-SFC/SFGG expert recommendations for the emergency management of older patients with acute heart failure. Part 2: Therapeutics, pathway of care and ethics.

Author

Peschanski N, Zores F, Boddaert J, Douay B, Delmas C, Broussier A, Douillet D, Berthelot E, Gilbert T, Gil-Jardiné C, Auffret V, Joly L, Guénézan J, Galinier M, Pépin M, Le Borgne P, Le Conte P, Girerd N, Roca F, Oberlin M, Jourdain P, Rousseau G, Lamblin N, Villoing B, Mouquet F, Dubucs X, Roubille F, Jonchier M, Sabatier R, Laribi S, Salvat M, Chouihed T, Bouillon-Minois JB, and Chauvin A

Published
2024
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35. Urinary proteomic signature of mineralocorticoid receptor antagonism by spironolactone: evidence from the HOMAGE trial.

Author

Yu YL, Siwy J, An DW, González A, Hansen T, Latosinska A, Pellicori P, Ravassa S, Mariottoni B, Verdonschot JA, Ahmed F, Petutschnigg J, Rossignol P, Heymans S, Cuthbert JJ, Girerd N, Clark AL, Verhamme P, Nawrot TS, Janssens S, Cleland JG, Zannad F, Diez J, Mischak H, Ferreira JP, and Staessen JA

Subjects
Humans, Male, Female, Aged, Middle Aged, Peptide Fragments blood, Peptide Fragments urine, Procollagen blood, Treatment Outcome, Fibrosis, Collagen Type I, alpha 1 Chain, Spironolactone therapeutic use, Mineralocorticoid Receptor Antagonists therapeutic use, Heart Failure drug therapy, Heart Failure metabolism, Proteomics methods, Biomarkers urine, Biomarkers blood, Collagen Type I urine, Collagen Type I blood
Abstract

Objective: Heart failure (HF) is characterised by collagen deposition. Urinary proteomic profiling (UPP) followed by peptide sequencing identifies parental proteins, for over 70% derived from collagens. This study aimed to refine understanding of the antifibrotic action of spironolactone., Methods: In this substudy (n=290) to the Heart 'Omics' in Ageing Study trial, patients were randomised to usual therapy combined or not with spironolactone 25-50 mg/day and followed for 9 months. The analysis included 1498 sequenced urinary peptides detectable in ≥30% of patients and carboxyterminal propeptide of procollagen I (PICP) and PICP/carboxyterminal telopeptide of collagen I (CITP) as serum biomarkers of COL1A1 synthesis. After rank normalisation of biomarker distributions, between-group differences in their changes were assessed by multivariable-adjusted mixed model analysis of variance. Correlations between the changes in urinary peptides and in serum PICP and PICP/CITP were compared between groups using Fisher's Z transform., Results: Multivariable-adjusted between-group differences in the urinary peptides with error 1 rate correction were limited to 27 collagen fragments, of which 16 were upregulated (7 COL1A1 fragments) on spironolactone and 11 downregulated (4 COL1A1 fragments). Over 9 months of follow-up, spironolactone decreased serum PICP from 81 (IQR 66-95) to 75 (61-90) µg/L and PICP/CITP from 22 (17-28) to 18 (13-26), whereas no changes occurred in the control group, resulting in a difference (spironolactone minus control) expressed in standardised units of -0.321 (95% CI 0.0007). Spironolactone did not affect the correlations between changes in urinary COL1A1 fragments and in PICP or the PICP/CITP ratio., Conclusions: Spironolactone decreased serum markers of collagen synthesis and predominantly downregulated urinary collagen-derived peptides, but upregulated others. The interpretation of these opposite UPP trends might be due to shrinking the body-wide pool of collagens, explaining downregulation, while some degree of collagen synthesis must be maintained to sustain vital organ functions, explaining upregulation. Combining urinary and serum fibrosis markers opens new avenues for the understanding of the action of antifibrotic drugs., Trial Registration Number: NCT02556450., Competing Interests: Competing interests: JS and AL are employees of Mosaiques-Diagnostics, Hanover, Germany. HM is the co-founder and co-owner of Mosaiques-Diagnostics. The other authors declare no conflict of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2024
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36. Management of Pulmonary Congestion in Patients With Aortic Stenosis: A Need for Improvement.

Author

Girerd N and Pibarot P

Subjects
Humans, Treatment Outcome, Hemodynamics, Risk Factors, Aortic Valve Stenosis diagnostic imaging, Aortic Valve Stenosis surgery, Aortic Valve Stenosis physiopathology, Aortic Valve Stenosis complications, Pulmonary Edema etiology, Pulmonary Edema diagnostic imaging, Pulmonary Edema therapy
Abstract

Competing Interests: Funding Support and Author Disclosures Dr Girerd has received honoraria from AstraZeneca, Bayer, Boehringer, Echosens, Lilly, Novartis, NP Medical, Novonordisk, and Roche Diagnostics. Dr Pibarot has received grants from Edwards Lifesciences, Medtronic, Novartis, and Pi-Cardia.

Published
2024
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37. 2023 SFMU/GICC-SFC/SFGG expert recommendations for the emergency management of older patients with acute heart failure. Part 1: Prehospital management and diagnosis.

Author

Peschanski N, Zores F, Boddaert J, Douay B, Delmas C, Broussier A, Douillet D, Berthelot E, Gilbert T, Gil-Jardiné C, Auffret V, Joly L, Guénézan J, Galinier M, Pépin M, Le Conte P, Girerd N, Roca F, Oberlin M, Jourdain P, Rousseau G, Lamblin N, Villoing B, Mouquet F, Dubucs X, Roubille F, Jonchier M, Sabatier R, Laribi S, Salvat M, Chouihed T, Bouillon-Minois JB, Chauvin A, and Le Borgne P

Published
2024
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39. Association of ventricular-arterial coupling with biomarkers involved in heart failure pathophysiology - the STANISLAS cohort.

Author

Holm H, Magnusson M, Jujić A, Lagrange J, Bozec E, Lamiral Z, Bresso E, Huttin O, Baudry G, Monzo L, Rossignol P, Zannad F, and Girerd N

Abstract

Aims: Impaired left ventricular-arterial coupling (VAC) has been shown to correlate with worse prognosis in cardiac diseases and heart failure (HF). The extent of the relationship between VAC and circulating biomarkers associated with HF has been scarcely documented. We aimed to explore associations of VAC with proteins involved in HF pathophysiology within a large population-based cohort of middle-aged individuals., Methods and Results: In the forth visit of the STANISLAS family cohort, involving 1309 participants (mean age 48 ± 14 years; 48% male) from parent and children generations, we analysed the association of 32 HF-related proteins with non-invasively assessed VAC using pulse wave velocity (PWV)/global longitudinal strain (GLS) and arterial elastance (E a )/ventricular end-systolic elastance (E es ). Among the 32 tested proteins, fatty acid-binding protein adipocyte 4, interleukin-6, growth differentiation factor 15, matrix metalloproteinase (MMP)-1, and MMP-9 and adrenomedullin were positively associated with PWV/GLS whereas transforming growth factor beta receptor type 3, MMP-2 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were negatively associated. In multivariable models, only MMP-2 and NT-proBNP were significantly and inversely associated with PWV/GLS in the whole population and in the parent generation. Higher levels of NT-proBNP were also negatively associated with E a /E es in the whole cohort but this association did not persist in the parent subgroup., Conclusion: Elevated MMP-2 and NT-proBNP levels correlate with better VAC (lower PWV/GLS), possibly indicating a compensatory cardiovascular response to regulate left ventricular pressure amidst cardiac remodelling and overload., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Published
2024
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40. Prognostic implication of lung ultrasound in heart failure: a pooled analysis of international cohorts.

Author

Rastogi T, Gargani L, Pellicori P, Lamiral Z, Ambrosio G, Bayés-Genis A, Domingo M, Lupon J, Simonovic D, Pugliese NR, Ruocco G, Duarte K, Coiro S, Palazzuoli A, and Girerd N

Subjects
Humans, Female, Male, Prognosis, Aged, Lung diagnostic imaging, Middle Aged, Risk Assessment, Cohort Studies, Stroke Volume physiology, Heart Failure diagnostic imaging, Heart Failure mortality, Ultrasonography methods
Abstract

Aims: Lung ultrasound (LUS) is often used to assess congestion in heart failure (HF). In this study, we assessed the prognostic role of LUS in patients with HF at admission and hospital discharge, and in an outpatient setting, and explored whether clinical factors [age, sex, left ventricular ejection fraction (LVEF), and atrial fibrillation] impact the prognostic value of LUS findings. Further, we assessed the incremental prognostic value of LUS on top of the following two clinical risk scores: (i) the atrial fibrillation, haemoglobin, elderly, abnormal renal parameters, diabetes mellitus (AHEAD) and (ii) the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) clinical risk scores., Methods and Results: We pooled data on patients hospitalized for HF or followed up in outpatient clinics from international cohorts. We enrolled 1947 patients at admission (n = 578), discharge (n = 389), and in outpatient clinics (n = 980). The total LUS B-line count was calculated for the eight-zone scanning protocol. The primary outcome was a composite of rehospitalization for HF and all-cause death. Compared with those in the lower tertiles of B lines, patients in the highest tertiles were older, more likely to have signs of HF and had higher N-terminal pro b-type natriuretic peptide (NT-proBNP) levels. A higher number of B lines was associated with increased risk of primary outcome at discharge [Tertile 3 vs. Tertile 1: adjusted hazard ratio (HR): 5.74 (3.26-10.12), P < 0.0001] and in outpatients [Tertile 3 vs. Tertile 1: adjusted HR: 2.66 (1.08-6.54), P = 0.033]. Age and LVEF did not influence the prognostic capacity of LUS in different clinical settings. Adding B-line count to the MAGGIC and AHEAD scores improved net reclassification significantly in all three clinical settings., Conclusion: A higher number of B lines in patients with HF was associated with an increased risk of morbidity and mortality, regardless of the clinical setting., Competing Interests: Conflict of interest: N.G. is supported by the French National Research Agency Fighting Heart Failure (ANR-15-RHU-0004), the French PIA project Lorraine Université d’Excellence GEENAGE (ANR-15-IDEX-04-LUE) programmes, and the Contrat de Plan Etat Région Lorraine and FEDER IT2MP; and has received honoraria from AstraZeneka, Bayer, Boehringer, Lilly, Novartis, and Vifor. L.G. is supported by Italian Ministry of Health and Regione Toscana; and has received personal fees from GE Healthcare, Phillips Healthcare, and Caption Health. A.B.-G. has received grant and non-financial support from Boehringer Ingelheim; and personal fees from Abbott, AstraZeneca, Boehringer Ingelheim, Novartis, Vifor, Roche Diagnostics, and Critical diagnostics. All other authors have reported that they have no relationships relevant to the contents of this study to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

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2024
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41. Heart rate reactivity, recovery, and endurance of the incremental shuttle walk test in patients prone to heart failure.

Author

Wei FF, Mariottoni B, An DW, Pellicori P, Yu YL, Verdonschot JAJ, Liu C, Ahmed FZ, Petutschnigg J, Rossignol P, Heymans S, Cuthbert J, Girerd N, Li Y, Clark AL, Nawrot TS, Ferreira JP, Zannad F, Cleland JGF, and Staessen JA

Abstract

Aims: Few randomized trials assessed the changes over time in the chronotropic heart rate (HR) reactivity (CHR), HR recovery (HRR) and exercise endurance (EE) in response to the incremental shuttle walk test (ISWT). We addressed this issue by analysing the open HOMAGE (Heart OMics in Aging) trial., Methods: In HOMAGE, 527 patients prone to heart failure were randomized to usual treatment with or without spironolactone (25-50 mg/day). The current sub-study included 113 controls and 114 patients assigned spironolactone (~70% on beta-blockers), who all completed the ISWT at baseline and at Months 1 and 9. Within-group changes over time (follow-up minus baseline) and between-group differences at each time point (spironolactone minus control) were analysed by repeated measures ANOVA, unadjusted or adjusted for sex, age and body mass index, and additionally for baseline for testing 1 and 9 month data., Results: Irrespective of randomization, the resting HR and CHR did not change from baseline to follow-up, with the exception of a small decrease in the HR immediately post-exercise (-3.11 b.p.m.) in controls at Month 9. In within-group analyses, HR decline over the 5 min post-exercise followed a slightly lower course at the 1 month visit in controls and at the 9 month visits in both groups, but not at the 1 month visit in the spironolactone group. Compared with baseline, EE increased by two to three shuttles at Months 1 and 9 in the spironolactone group but remained unchanged in the control group. In the between-group analyses, irrespective of adjustment, there were no HR differences at any time point from rest up to 5 min post-exercise or in EE. Subgroup analyses by sex or categorized by the medians of age, left ventricular ejection fraction or glomerular filtration rate were confirmatory. Combining baseline and Months 1 and 9 data in both treatment groups, the resting HR, CHR and HRR at 1 and 5 min averaged 61.5, 20.0, 9.07 and 13.8 b.p.m. and EE 48.3 shuttles., Conclusions: Spironolactone on top of usual treatment compared with usual treatment alone did not change resting HR, CHR, HRR and EE in response to ISWT. Beta-blockade might have concealed the effects of spironolactone. The current findings demonstrate that the ISWT, already used in a wide variety of pathological conditions, is a practical instrument to measure symptom-limited exercise capacity in patients prone to developing heart failure because of coronary heart disease., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

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2024
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42. Diuresis Efficacy in Ambulatory Congested Heart Failure Patients: Intrapatient Comparison of 3 Diuretic Regimens (DEA-HF).

Author

Abbo AR, Gruber A, Volis I, Aronson D, Girerd N, Lund Kristensen S, Zukermann R, Alberkant N, Sitnitsky E, Kruger A, Khasis P, Bravo E, Elad B, Helmer Levin L, and Caspi O

Subjects
Humans, Male, Female, Aged, Prospective Studies, Middle Aged, Drug Therapy, Combination, Diuresis drug effects, Treatment Outcome, Heart Failure drug therapy, Heart Failure physiopathology, Furosemide administration & dosage, Furosemide therapeutic use, Diuretics administration & dosage, Diuretics therapeutic use, Acetazolamide administration & dosage, Acetazolamide therapeutic use, Metolazone administration & dosage, Cross-Over Studies
Abstract

Background: Limited evidence exists regarding efficacy and safety of diuretic regimens in ambulatory, congestion-refractory, chronic heart failure (CHF) patients., Objectives: The authors sought to compare the potency and safety of commonly used diuretic regimens in CHF patients., Methods: A prospective, randomized, open-label, crossover study conducted in NYHA functional class II to IV CHF patients, treated in an ambulatory day-care unit. Each patient received 3 different diuretic regimens: intravenous (IV) furosemide 250 mg; IV furosemide 250 mg plus oral metolazone 5 mg; and IV furosemide 250 mg plus IV acetazolamide 500 mg. Treatments were administered once a week, in 1 of 6 randomized sequences. The primary endpoint was total sodium excretion, and the secondary was total urinary volume excreted, both measured for 6 hours post-treatment initiation., Results: A total of 42 patients were recruited. Administration of furosemide plus metolazone resulted in the highest weight of sodium excreted, 4,691 mg (95% CI: 4,153-5,229 mg) compared with furosemide alone, 3,835 mg (95% CI: 3,279-4,392 mg; P = 0.015) and to furosemide plus acetazolamide 3,584 mg (95% CI: 3,020-4,148 mg; P = 0.001). Furosemide plus metolazone resulted in 1.84 L of urine (95% CI: 1.63-2.05 L), compared with 1.58 L (95% CI: 1.37-1.8); P = 0.039 collected following administration of furosemide plus acetazolamide and 1.71 L (95% CI: 1.49-1.93 L) following furosemide alone. The incidence of worsening renal function was significantly higher when adding metolazone (39%) to furosemide compared with furosemide alone (16%) and to furosemide plus acetazolamide (2.6%) (P < 0.001)., Conclusions: In ambulatory CHF patients, furosemide plus metolazone resulted in a significantly higher natriuresis compared with IV furosemide alone or furosemide plus acetazolamide., Competing Interests: Funding Support and Author Disclosures Dr Abbo has been a consultant for Edwards Life Sciences; and has received speaker honoraria from Boehringer Ingelheim. Dr Kristensen has been a consultant for Bayer; and has received speaker honoraria from AstraZeneca. Dr Caspi has received speaker honoraria from AstraZeneca, Novo Nordisk, and Pfizer; and has received consultancy honoraria from Vectorious medical technologies. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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2024
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43. Dietary inflammatory potential and arterial stiffness in a French cohort: Insights from the STANISLAS study.

Author

Agbo LD, Girerd N, Lamiral Z, Duarte K, Bozec E, Merckle L, Hoge A, Guillaume M, Laville M, Nazare JA, Rossignol P, Boivin JM, and Wagner S

Subjects
Humans, Cross-Sectional Studies, Male, Female, Middle Aged, France epidemiology, Adult, Risk Factors, Inflammation Mediators blood, Risk Assessment, Diet, Healthy, Nutritive Value, Aged, Pulse Wave Analysis, Vascular Stiffness, Inflammation diagnosis, Inflammation physiopathology, Inflammation epidemiology, Carotid-Femoral Pulse Wave Velocity, Diet adverse effects
Abstract

Background and Aims: Chronic inflammation plays a key role in arterial stiffness pathogenesis. Dietary components can display anti- or pro-inflammatory properties. Nonetheless, the association between the diet's overall inflammatory potential and arterial stiffness is unclear. This study aimed to assess the association between the diet's overall inflammatory potential and arterial stiffness assessed by carotid-femoral pulse wave velocity (cfPWV)., Methods and Results: This cross-sectional study included 1307 participants from the STANISLAS family cohort study. Dietary data were collected using a validated food frequency questionnaire. The adapted dietary inflammatory index (ADII) score was calculated to assess the inflammatory potential of the participants' diet. The association of ADII score quartile with cfPWV was assessed using IPW-weighted linear mixed models with random family effect. The median (Q1-Q3) ADII score was 0.45 (-1.57, 2.04). Participants exhibiting higher ADII scores demonstrated elevated energy intake, dietary saturated fat, and ultra-processed foods. Conversely, individuals with lower ADII scores exhibited higher vitamins and omega intakes, and a higher diet quality, as assessed by the DASH score. Despite these observations from the descriptive analyses, ADII score quartiles were not significantly associated with cfPWV (β(95% CI) were 0.01 (-0.02,0.04) for Q2, 0.02 (-0.01,0.05) for Q3, and 0.02 (-0.01,0.05) for Q4 compared to Q1)., Conclusion: In this cross-sectional study, participants had a relatively modest consumption of pro-inflammatory foods, no substantial associations were observed between the diet inflammatory potential and arterial stiffness. Further longitudinal studies in larger cohorts are needed to better understand the link between inflammatory diet and arterial stiffness., Competing Interests: Declaration of competing interest NG received honoraria from AstraZeneca, Bayer, Boehringer, Echosens, Lilly, Roche diagnostics, Novartis. PR: reports consulting for Idorsia, G3P, honoraria from AstraZeneca, Bayer, Boehringer-Ingelheim, Cincor, CVRx, Fresenius, KBP biosciences, Novartis, NovoNordisk, Relypsa, Servier, and Vifor Fresenius Medical Care Renal Pharma; and travel grants from AstraZeneca, Bayer, CVRx, Novartis, and Vifor Fresenius Medical Care Renal Pharma; Cofounder: CardioRenal. The other co-authors have no conflicts of interest to disclose related to the submitted work., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

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2024
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44. Advanced myocardial deformation echocardiography for evaluation of the athlete's heart: Functional and mechanistic analysis.

Author

Colne E, Pace N, Fraix A, Gauthier F, Selton-Suty C, Chenuel B, Sadoul N, Girerd N, Lamiral Z, Felloni J, Djaballah K, Filippetti L, and Huttin O

Subjects
Humans, Male, Adult, Young Adult, Reproducibility of Results, Case-Control Studies, France, Ventricular Remodeling, Myocardial Contraction, Exercise Tolerance, Ventricular Function, Left, Predictive Value of Tests, Athletes, Cardiomegaly, Exercise-Induced, Stroke Volume, Ventricular Dysfunction, Left physiopathology, Ventricular Dysfunction, Left diagnostic imaging
Abstract

Background: Assessment of the athlete's heart is challenging because of a phenotypic overlap between reactive physiological adaptation and pathological remodelling. The potential value of myocardial deformation remains controversial in identifying early cardiomyopathy., Aim: To identify the echocardiographic phenotype of athletes using advanced two-dimensional speckle tracking imaging, and to define predictive factors of subtle left ventricular systolic dysfunction., Methods: In total, 191 healthy male athletes who underwent a preparticipation medical evaluation at Nancy University Hospital between 2013 and 2020 were included. Clinical and echocardiographic data were compared with 161 healthy male subjects from the STANISLAS cohort. Borderline global longitudinal strain value was defined as<17.5%., Results: Athletes demonstrated lower left ventricular ejection fraction (57.9±5.3% vs. 62.6±6.4%; P<0.01) and lower global longitudinal strain (17.5±2.2% vs. 21.1±2.1%; P<0.01). No significant differences were found between athletes with and without a borderline global longitudinal strain value regarding clinical characteristics, structural echocardiographic features and exercise capacity. A borderline global longitudinal strain value was associated with a lower endocardial global longitudinal strain (18.8±1.2% vs. 22.7±1.9%; P=0.02), a lower epicardial global longitudinal strain (14.0±1.1% vs. 16.6±1.2%; P<0.01) and a higher endocardial/epicardial global longitudinal strain ratio (1.36±0.07 vs. 1.32±0.06; P<0.01). No significant difference was found regarding mechanical dispersion (P=0.46)., Conclusions: Borderline global longitudinal strain value in athletes does not appear to be related to structural remodelling, mechanical dispersion or exercise capacity. The athlete's heart is characterized by a specific myocardial deformation pattern with a more pronounced epicardial layer strain impairment., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

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2024
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45. Poor in-hospital congestion improvement in acute heart failure patients classified according to left ventricular ejection fraction: prognostic implications.

Author

Ruocco G, Girerd N, Rastogi T, Lamiral Z, and Palazzuoli A

Subjects
Humans, Male, Female, Prognosis, Aged, Aged, 80 and over, Acute Disease, Echocardiography, Risk Assessment, Hospitalization statistics & numerical data, Cohort Studies, Heart Failure physiopathology, Heart Failure diagnostic imaging, Heart Failure complications, Heart Failure mortality, Stroke Volume physiology
Abstract

Aims: Residual congestion in acute heart failure (AHF) is associated with poor prognosis. However, there is a lack of data on the prognostic value of changes in a combined assessment of in-hospital congestion. The present study sought to assess the association between in-hospital congestion changes and subsequent prognosis according to left ventricular ejection fraction (LVEF) classification., Methods and Results: Patients (N = 244, 80.3 ± 7.6 years, 50.8% male) admitted for acute HF in two European tertiary care centres underwent clinical assessment (congestion score included dyspnoea at rest, rales, third heart sound, jugular venous distention, peripheral oedema, and hepatomegaly; simplified congestion score included rales and peripheral oedema), echocardiography, lung ultrasound, and natriuretic peptides (NP) measurement at admission and discharge. The primary outcome was a composite of all-cause mortality and/or HF re-hospitalization. In the 244 considered patients (95 HF with reduced EF, 57 HF with mildly reduced EF, and 92 HF with preserved EF), patients with limited improvement in clinical congestion score (hazard ratio 2.33, 95% CI 1.51-3.61, P = 0.0001), NP levels (2.29, 95% CI 1.55-3.38, P < 0.0001), and the number of B-lines (6.44, 95% CI 4.19-9.89, P < 0.001) had a significantly higher risk of outcome compared with patients experiencing more sizeable decongestion. The same pattern of association was observed when adjusting for confounding factors. A limited improvement in clinical congestion score and in the number of B-lines was related to poor prognosis for all LVEF categories., Conclusion: In AHF, the degree of congestion reduction assessed over the in-hospital stay period can stratify the subsequent event risk. Limited reduction in both clinical congestion and B-lines number are related to poor prognosis, irrespective of HF subtype., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

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2024
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46. Multiomic profiling of new-onset kidney function decline: insights from the STANISLAS study cohort with a 20-year follow-up.

Author

Dupont V, Xhaard C, Behm-Ansmant I, Bresso E, Thuillier Q, Branlant C, Lopez-Sublet M, Deleuze JF, Zannad F, Girerd N, and Rossignol P

Abstract

Background: Identifying the biomarkers associated with new-onset glomerular filtration rate (GFR) decrease in an initially healthy population could offer a better understanding of kidney function decline and help improving patient management., Methods: Here we described the proteomic and transcriptomic footprints associated with new-onset kidney function decline in an initially healthy and well-characterized population with a 20-year follow-up. This study was based on 1087 individuals from the familial longitudinal Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux (STANISLAS) cohort who attended both visit 1 (from 1993 to 1995) and visit 4 (from 2011 to 2016). New-onset kidney function decline was approached both in quantitative (GFR slope for each individual) and qualitative (defined as a decrease in GFR of >15 ml/min/1.7 m 2 ) ways. We analysed associations of 445 proteins measured both at visit 1 and visit 4 using Olink Proseek ® panels and 119 765 genes expressions measured at visit 4 with GFR decline. Associations were assessed using multivariable models. The Bonferroni correction was applied., Results: We found several proteins (including PLC, placental growth factor (PGF), members of the tumour necrosis factor receptor superfamily), genes (including CCL18, SESN3 ), and a newly discovered miRNA-mRNA pair (MIR1205-DNAJC6) to be independently associated with new-onset kidney function decline. Complex network analysis highlighted both extracellular matrix and cardiovascular remodelling (since visit 1) as well as inflammation (at visit 4) as key features of early GFR decrease., Conclusions: These findings lay the foundation to further assess whether the proteins and genes herein identified may represent potential biomarkers or therapeutic targets to prevent renal function impairment., Competing Interests: The authors have nothing to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Published
2024
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47. Iron deficiency and supplementation in patients with heart failure: Results from the IRON-HF international survey.

Author

Camilli M, Ballacci F, Rossi VA, Cannatà A, Monzo L, Mewton N, Girerd N, Gentile P, Marini M, Mapelli M, Flammer AJ, Aspromonte N, Montone RA, Lombardo A, Lanza GA, Savarese G, Ruschitzka F, and Crea F

Abstract

Aims: Iron deficiency (ID) is common in patients with heart failure (HF) and is associated with poor outcomes, regardless of anaemia status. Iron supplementation has been demonstrated to improve exercise capacity and quality of life in patients with HF with an ejection fraction <50% and ID. This survey aimed to provide data on real-world practices related to ID screening and management., Methods and Results: We designed and distributed an online survey (23 questions) regarding ID screening and management in the HF setting. Overall, 256 cardiologists completed the survey (59.8% male, mostly between 30 and 50 years). The majority of physicians defined ID according to the most recent HF recommendations (98.4%) and reported screening for ID in more than half of their patients (68.4%). However, only 54.3% of the respondents performed periodic screening (every 6 months to 1 year). A total of 93.0% of participants prescribed and/or administered iron supplementation, using intravenous iron as the preferred method of administration (86.3%). After iron supplementation, 96.1% of the respondents reassessed ID, most frequently at 3-6 months (67.6%). Most physicians (93.8%) perceived ID as an underestimated comorbidity in HF. Cardiologists' age, training status, subspecialty and work setting (academic vs. non-academic hospitals) were associated with heterogeneity in the answers., Conclusions: The results of this survey highlight the need for more consistent strategies of ID screening and treatment for patients with HF., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Published
2024
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48. MASLD and MASH at the crossroads of hepatology trials and cardiorenal metabolic trials.

Author

Zannad F, Sanyal AJ, Butler J, Ferreira JP, Girerd N, Miller V, Pandey A, Parikh CR, Ratziu V, Younossi ZM, and Harrison SA

Subjects
Humans, Cardiovascular Diseases, Fatty Liver therapy, Biomarkers, Renal Insufficiency, Chronic therapy, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 drug therapy, Clinical Trials as Topic
Abstract

Steatotic liver disease (SLD) is a worldwide public health problem, causing considerable morbidity and mortality. Patients with SLD are at increased risk for major adverse cardiovascular (CV) events, type 2 diabetes mellitus and chronic kidney disease. Conversely, patients with cardiometabolic conditions have a high prevalence of SLD. In addition to epidemiological evidence linking many of these conditions, there is evidence of shared pathophysiological processes. In December 2022, a unique multi-stakeholder, multi-specialty meeting, called MOSAIC (Metabolic multi Organ Science Accelerating Innovation in Clinical Trials) was convened to foster collaboration across metabolic, hepatology, nephrology and CV disorders. One of the goals of the meeting was to consider approaches to drug development that would speed regulatory approval of treatments for multiple disorders by combining liver and cardiorenal endpoints within a single study. Non-invasive tests, including biomarkers and imaging, are needed in hepatic and cardiorenal trials. They can be used as trial endpoints, to enrich trial populations, to diagnose and risk stratify patients and to assess treatment efficacy and safety. Although they are used in proof of concept and phase 2 trials, they are often not acceptable for regulatory approval of therapies. The challenge is defining the optimal combination of biomarkers, imaging and morbidity/mortality outcomes and ensuring that they are included in future trials while minimizing the burden on patients, trialists and trial sponsors. This paper provides an overview of some of the wide array of CV, liver and kidney measurements that were discussed at the MOSAIC meeting., (© 2024 The Association for the Publication of the Journal of Internal Medicine.)

Published
2024
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49. Hypothermia in patients with cardiac arrest prior to ECMO-VA: Insight from the HYPO-ECMO trial.

Author

Levy B, Girerd N, Duarte K, Antoine ML, Monzo L, Ouattara A, Delmas C, Brodie D, Combes A, Kimmoun A, and Baudry G

Subjects
Humans, Male, Female, Middle Aged, Aged, Extracorporeal Membrane Oxygenation methods, Hypothermia, Induced methods, Heart Arrest therapy, Heart Arrest mortality, Heart Arrest complications, Shock, Cardiogenic therapy, Shock, Cardiogenic etiology, Shock, Cardiogenic mortality
Abstract

Aim: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has become a common intervention for patients with cardiogenic shock (CS), often complicated by cardiac arrest (CA). Moderate hypothermia (MH) has shown promise in mitigating ischemia-reperfusion injury following CA. The HYPO-ECMO trial aimed to compare the effect of MH versus normothermia in refractory CS rescued by VA-ECMO. The primary aim of this non-predefined post hoc study was to assess the treatment effect of MH in the subgroup of patients with cardiac arrest (CA) within the HYPO-ECMO trial. Additionally, we will evaluate the prognostic significance of CA in these patients., Methods: This post hoc analysis utilized data from the randomized HYPO-ECMO trial conducted across 20 French cardiac shock care centers between October 2016 and July 2019. Participants included intubated patients receiving VA-ECMO for CS for less than 6 h, with 334 patients completing the trial. Patients were randomized to early MH (33-34 °C) or normothermia (36-37 °C) for 24 h., Results: Of the 334 patients, 159 (48%) experienced preceding CA. Mortality in the CA group was 50.9% at 30 days and 59.1% at 180 days, compared to 42.3% and 51.4% in the no-CA group, respectively (adjusted risk difference [RD] at 30 days, 8.1% [-0.8 to 17.1%], p = 0.074 and RD at 180 days 7.0% [-3.0 to 16.9%], p = 0.17). MH was associated with a significant reduction in primary (RD -13.3% [-16.3 to -0.3%], p = 0.031) and secondary outcomes in the CA group only (p < 0.025 for all), with a significant interaction between MH and CA status for 180-day mortality [p = 0.03]., Conclusions: This post hoc analysis suggests that MH shows potential for reducing mortality and composite endpoints in patients with cardiac arrest and refractory CS treated with VA-ECMO without an increased risk of severe bleeding or infection. Further research is needed to validate these findings and elucidate underlying mechanisms., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Pr. Levy reported receiving personal fees from Abiomed, Gettinge, Baxter, Novartis, Sanofi, Amomed, and Orion, outside the submitted work. Pr. Girerd reported receiving personal fees from Novartis, Bayer, AstraZeneca, Lilly, Boehringer, and Vifor, outside the submitted work. Dr. Duarte reported no conflicts of interest regarding this work. Dr. Marie-Lauren Antoine reported no conflicts of interest regarding this work. Mrs. Dr. Monzo reported receiving personal fees from AstraZeneca and Vifor, outside the submitted work. Dr. Ouattara reported receiving personal fees from Abiomed, Nordic Pharma, LFB, VifOR Pharma, Orion Pharma, ISEP, Masimo, and Medtronic. Dr. Delmas reported receiving personal fees from Abiomed and Abbott Laboratories. Pr. Brodie reports receiving research support from and consults for LivaNova. He has been on the medical advisory boards for Abiomed, Xenios, Medtronic, Inspira and Cellenkos. He is the President-elect of the Extracorporeal Life Support Organization (ELSO) and the Chair of the Executive Committee of the International ECMO Network (ECMONet), and he writes for UpToDate. Pr. Combes reported receiving personal fees from Getinge, Baxter, and Fresenius-Xenios, outside the submitted work. Pr. Kimmoun reported no conflicts of interest regarding this work. Dr. Baudry reported receiving personal fees from Abbott, AstraZeneca, and Boehringer, outside the submitted work., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Published
2024
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