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1. Ventricular–arterial coupling (VAC) in a population-based cohort of middle-aged individuals: The STANISLAS cohort

Author: Holm, H., Magnusson, M., Jujić, A., Pugliese, Nicola Riccardo, Bozec, E., Lamiral, Z., Huttin, O., Zannad, F., Rossignol, P., and Girerd, N.
Published: 2023
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2. The current best drug treatment for hypertensive heart failure with preserved ejection fraction

Author: Rist, A, Sevre, K, Wachtell, K, Devereux, R, Aurigemma, G, Smiseth, O, Kjeldsen, S, Julius, S, Pitt, B, Burnier, M, Kreutz, R, Oparil, S, Mancia, G, Zannad, F, Rist A., Sevre K., Wachtell K., Devereux R. B., Aurigemma G. P., Smiseth O. A., Kjeldsen S. E., Julius S., Pitt B., Burnier M., Kreutz R., Oparil S., Mancia G., Zannad F., Rist, A, Sevre, K, Wachtell, K, Devereux, R, Aurigemma, G, Smiseth, O, Kjeldsen, S, Julius, S, Pitt, B, Burnier, M, Kreutz, R, Oparil, S, Mancia, G, Zannad, F, Rist A., Sevre K., Wachtell K., Devereux R. B., Aurigemma G. P., Smiseth O. A., Kjeldsen S. E., Julius S., Pitt B., Burnier M., Kreutz R., Oparil S., Mancia G., and Zannad F.
Abstract: More than 90 % of patients developing heart failure (HF) have hypertension. The most frequent concomitant conditions are type-2 diabetes mellitus, obesity, atrial fibrillation, and coronary disease. HF outcome research focuses on decreasing mortality and preventing hospitalization for worsening HF syndrome. All drugs that decrease these HF endpoints lower blood pressure. Current drug treatments for HF are (i) angiotensin-converting enzyme inhibitors, angiotensin receptor blockers or angiotensin receptor neprilysin inhibitors, (ii) selected beta-blockers, (iii) steroidal and non-steroidal mineralocorticoid receptor antagonists, and (iv) sodium-glucose cotransporter 2 inhibitors. For various reasons, these drug treatments were first studied in HF patients with a reduced ejection fraction (HFrEF). Subsequently, they have been investigated in HF patients with a preserved left ventricular ejection fraction (LVEF, HFpEF) of mostly hypertensive etiology, and with modest benefits largely assessed on top of background treatment with the drugs already proven effective in HFrEF. Additionally, diuretics are given on symptomatic indications. Patients with HFpEF may have diastolic dysfunction but also systolic dysfunction visualized by lack of longitudinal shortening. Considering the totality of evidence and the overall need for antihypertensive treatment and/or treatment of hypertensive complications in almost all HF patients, the principal drug treatment of HF appears to be the same regardless of LVEF. Rather than LVEF-guided treatment of HF, treatment of HF should be directed by symptoms (related to the level of fluid retention), signs (tachycardia), severity (NYHA functional class), and concomitant diseases and conditions. All HF patients should be given all the drug classes mentioned above if well tolerated.
Published: 2024

3. 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: Packer, M, Anker, S, Butler, J, Filippatos, G, Pocock, S, Zannad, F, Ferreira, JP, Brueckmann, M, George, J, Jamal, W, Welty, FK, Palmer, M, Clayton, T, Parhofer, KG, Pedersen, TR, Greenberg, B, Konstam, MA, Lees, KR, 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, Verma, S, Zhang, J, Spinar, J, Seronde, M-F, Boehm, M, Merkely, B, Chopra, V, Senni, M, Taddi, S, Tsutsui, H, Choi, D-J, Chuquiure, E, La Rocca, HPB, Ponikowski, P, Juanatey, JRG, Squire, I, Januzzi, J, Pina, I, Bernstein, R, Cheung, A, Green, J, Kaul, S, Lam, C, Lip, G, Marx, N, McCullough, P, Mehta, C, Rosenstock, J, Sattar, N, 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 Márquez, L, Leon de la Fuente, RA, Mansilla, M, Hominal, M, Hasbani, E, Najenson, M, Moises Azize, G, Luquez, H, Guzman, L, Sessa, H, Amuchástegui, 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, LH, Vieira Moreira, MdC, de Souza, W, Backes, LM, Maia, L, De Souza Paolino, B, Manenti, ER, Saporito, W, Villaça Guimarães Filho, F, Franco Hirakawa, T, Saliba, LA, Neuenschwander, FC, de Freitas Zerbini, CA, Gonçalves, G, Gonçalves Mello, Y, Ascenção de Souza, J, Beck da Silva Neto, L, Bocchi, EA, Da Silveira, J, de Moura Xavier Moraes Junior, JB, de Souza Neto, JD, Hernandes, M, Finimundi, HC, Sampaio, CR, Vasconcellos, E, Neves Mancuso, FJ, Noya Rabelo, MM, Rodrigues Bacci, M, Santos, F, Vidotti, M, Simões, MV, Gomes, FL, Vieira Nascimento, C, Precoma, D, Helfenstein Fonseca, FA, Ribas Fortes, JA, Leães, PE, Campos de Albuquerque, D, Kerr Saraiva, JF, Rassi, S, Alves da Costa, FA, Reis, G, Zieroth, S, Dion, D, Savard, D, Bourgeois, R, Constance, C, Anderson, K, Leblanc, M-H, Yung, D, Swiggum, E, Pliamm, L, Pesant, Y, Tyrrell, B, Huynh, T, Spiegelman, J, Lavoie, J-P, 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-G, Genth-Zotz, S, Kemala, E, Lemke, B, Böhm, 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, CP, König, W, Maier, L, Menzel, F, Proskynitopoulos, N, Ebert, H-H, Sarnighausen, H-E, Düngen, H-D, Licka, M, Stellbrink, C, Winkelmann, B, Menck, N, López-Sendón, JL, de la Fuente Galán, L, Delgado Jiménez, JF, Manito Lorite, N, Pérez de Juan Romero, M, Galve Basilio, E, Cereto Castro, F, González Juanatey, JR, Gómez, JJ, Sanmartín Fernández, 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-L, Galinier, M, Roubille, F, Alexandre, J, Babuty, D, Delarche, N, Berneau, J-B, 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, RG, Toth, K, Szakal, I, Nagy, L, Barany, T, Nagy, A, Szolnoki, E, Chopra, VK, 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, NK, Mehta, A, Kashyap, J, Kothari, Y, TaddeI, S, Scherillo, M, Zacà, 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-J, Na, JO, Yoo, B-S, Choi, J-O, Hong, SK, Shin, J-H, Cho, M-C, Han, SH, Jeong, J-O, Kim, J-J, Kang, SM, Kim, D-S, Kim, MH, Llamas Esperon, G, Illescas Díaz, 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, FG, Rodriguez Briones, I, Chuquiure Valenzuela, EJJR, Aguilera Real, ME, Carrillo Calvillo, J, Alpizar Salazar, M, Cervantes Escárcega, JL, Velasco Sanchez, R, Al - Windy, N, van Heerebeek, L, Bellersen, L, Brunner-La Rocca, H-P, Post, J, Linssen, GCM, van de Wetering, M, Peters, R, van Stralen, R, Groutars, R, Smits, P, Yilmaz, A, Kok, WEM, Van der Meer, P, Dijkmans, P, Troquay, R, van Alem, AP, Van de Wal, R, Handoko, L, Westendorp, ICD, van Bergen, PFMM, Rensing, BJWM, Hoogslag, P, Kietselaer, B, Kragten, JA, den Hartog, FR, 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, Verma, Subodh, Dhingra, Nitish K, Butler, Javed, Anker, Stefan D, Ferreira, Joao Pedro, Filippatos, Gerasimos, Januzzi, James L, Lam, Carolyn S P, Sattar, Naveed, Peil, Barbara, Nordaby, Matias, Brueckmann, Martina, Pocock, Stuart J, Zannad, Faiez, and Packer, Milton
Published: 2022
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4. Patient-reported outcome measures and patient engagement in heart failure clinical trials: multi-stakeholder perspectives

Author: Zannad, F, Alikhaani, J, Alikhaani, S, Butler, J, Gordon, J, Jensen, K, Khatib, R, Mantovani, L, Martinez, R, Moore, W, Murakami, M, Roessig, L, Stockbridge, N, Van Spall, H, Yancy, C, Spertus, J, Zannad F., Alikhaani J., Alikhaani S., Butler J., Gordon J., Jensen K., Khatib R., Mantovani L., Martinez R., Moore W. F., Murakami M., Roessig L., Stockbridge N., Van Spall H. G. C., Yancy C., Spertus J. A., Zannad, F, Alikhaani, J, Alikhaani, S, Butler, J, Gordon, J, Jensen, K, Khatib, R, Mantovani, L, Martinez, R, Moore, W, Murakami, M, Roessig, L, Stockbridge, N, Van Spall, H, Yancy, C, Spertus, J, Zannad F., Alikhaani J., Alikhaani S., Butler J., Gordon J., Jensen K., Khatib R., Mantovani L., Martinez R., Moore W. F., Murakami M., Roessig L., Stockbridge N., Van Spall H. G. C., Yancy C., and Spertus J. A.
Abstract: There are many consequences of heart failure (HF), including symptoms, impaired health-related quality of life (HRQoL), and physical and social limitations (functional status). These have a substantial impact on patients' lives, yet are not routinely captured in clinical trials. Patient-reported outcomes (PROs) can quantify patients' experiences of their disease and its treatment. Steps can be taken to improve the use of PROs in HF trials, in regulatory and payer decisions, and in patient care. Importantly, PRO measures (PROMs) must be developed with involvement of patients, family members, and caregivers from diverse demographic groups and communities. PRO data collection should become more routine not only in clinical trials but also in clinical practice. This may be facilitated by the use of digital tools and interdisciplinary patient advocacy efforts. There is a need for standardization, not only of the PROM instruments, but also in procedures for analysis, interpretation and reporting PRO data. More work needs to be done to determine the degree of change that is important to patients and that is associated with increased risks of clinical events. This ‘minimal clinically important difference’ requires further research to determine thresholds for different PROMs, to assess consistency across trial populations, and to define standards for improvement that warrant regulatory and reimbursement approvals. PROs are a vital part of patient care and drug development, and more work should be done to ensure that these measures are both reflective of the patient experience and that they are more widely employed.
Published: 2023

5. Maintenance of serum potassium with sodium zirconium cyclosilicate (ZS-9) in heart failure patients: Results from a phase 3 randomized, double-blind, placebo-controlled trial

Author: Deedwania, Prakash, Anker, SD, Kosiborod, M, Zannad, F, Piña, IL, Mccullough, PA, Filippatos, G, van, P, Ponikowski, P, Rasmussen, HS, and Lavin, PT
Abstract: © 2015 European Society of Cardiology. Aims: Hyperkalaemia in heart failure patients limits use of cardioprotective renin-angiotensin-aldosterone system inhibitors (RAASi). Sodium zirconium cyclosilicate (ZS-9) is a selective potassium ion trap, whose mech
Published: 2015

6. Effect of eplerenone according to duration of heart failure in EMPHASIS-HF: It is never too late to start an MRA in HFrEF

Author: Matsumoto, S, primary, Kondo, T, additional, Jhund, P S, additional, Swedberg, K, additional, Veldhuisen, D J, additional, Vincent, J, additional, Pocock, S J, additional, Pitt, B, additional, Zannad, F, additional, and Mcmurray, J J V, additional
Published: 2023
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7. Effects of empaglifozin on collagen biomarkers in patients with heart failure. Results from the EMPEROR trials

Author: Ferreira, J, primary, Sumin, M, additional, Butler, J, additional, and Zannad, F, additional
Published: 2023
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8. Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Author: Maggioni, AP, Greene, SJ, Fonarow, GC, Bohm, M, Zannad, F, Solomon, SD, Lewis, EF, Baschiera, F, Hua, TA, Gimpelewicz, CR, Lesogor, A, Gheorghiade, M, Ramos, S, Luna, A, Miriuka, S, Diez, M, Perna, E, Luquez, H, Pinna, JG, Castagnino, J, Alvarenga, P, Ibanez, J, Blumberg, ES, Dizeo, C, Guerrero, RA, Schygiel, P, Milesi, R, Sosa, C, Hominal, M, Marquez, LL, Poy, C, Hasbani, E, Vico, M, Fernandez, A, Vita, N, Vanhaecke, J, De Keulenaer, G, Striekwold, H, Vervoort, G, Vrolix, M, Henry, P, Dendale, P, Smolders, W, Marechal, P, Vandekerckhove, H, Oliveira, M, Neuenschwande, F, Reis, G, Saraiva, J, Bodanese, L, Canesin, M, Greco, O, Bassan, R, Marino, RL, Giannetti, N, Moe, G, Sussex, B, Sheppard, R, Huynh, T, Stewart, R, Haddad, H, Echeverria, L, Quintero, A, Torres, A, Jaramillo, M, Lopez, M, Mendoza, F, Florez, N, Cotes, C, Garcia, M, Belohlavek, J, Hradec, J, Peterka, M, Gregor, P, Monhart, Z, Jansky, P, Kettner, J, Reichert, P, Spinar, J, Brabec, T, Hutyra, M, Solar, M, Pietila, M, Nyman, K, Pajari, R, Cohen, A, Galinier, M, Gosse, P, Livarek, B, Neuder, Y, Jourdain, P, Picard, F, Isnard, R, Hoppe, U, Kaeaeb, S, Rosocha, S, Prondzinsky, R, Felix, S, Duengen, H-D, and Figulla, H-R
Subjects: Heart Disease, Clinical Research, Clinical Trials and Supportive Activities, Diabetes, Cardiovascular, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Metabolic and endocrine, Administration, Oral, Amides, Cardiotonic Agents, Death, Sudden, Cardiac, Diabetic Cardiomyopathies, Double-Blind Method, Female, Fumarates, Heart Failure, Hospitalization, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Prospective Studies, Renin, Treatment Outcome, Aliskiren, Outcomes, Post-discharge, ASTRONAUT Investigators and Coordinators, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Cardiovascular System & Hematology
Abstract: AimsThe objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM).Methods and resultsASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction).ConclusionThis pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without DM.
Published: 2013

9. Combined baseline and one-month changes in big endothelin-1 and brain natriuretic peptide plasma concentrations predict clinical outcomes in patients with left ventricular dysfunction after acute myocardial infarction: Insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) study

Author: Olivier, A, Girerd, N, Michel, JB, Ketelslegers, JM, Fay, R, Vincent, J, Bramlage, P, Pitt, B, Zannad, F, and Rossignol, P
Published: 2017
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10. Clinic Versus Ambulatory Blood Pressure in Resistant Hypertension: Impact of Antihypertensive Medication Nonadherence: A Post Hoc Analysis the DENERHTN Study

Author: Hamdidouche, Idir, Gosse, Philippe, Cremer, Antoine, Lorthioir, Aurelien, Delsart, Pascal, Courand, Pierre-Yves, Denolle, Thierry, Halimi, Jean-Michel, Girerd, Xavier, Ormezzano, Olivier, Rossignol, Patrick, Pereira, Helena, Azizi, Michel, Amar, L, Bobrie, G, Monge, M, Pagny, JY, Sapoval, M, Claisse, G, Midulla, M, Mounier-Vehier, C, Dauphin, R, Fauvel, JP, Lantelme, P, Rouvière, O, Grenier, N, Lebras, Y, Trillaud, H, Dourmap, C, Heautot, JF, Larralde, A, Paillard, F, Cluzel, P, Rosenbaum, D, Alison, D, Popovic, B, Zannad, F, Baguet, JP, Thony, F, Bartoli, JM, Vaïsse, B, Drouineau, J, Herpin, D, Sosner, P, Tasu, JP, Velasco, S, Ribstein, J, Kovacsik, H, Bouhanick, B, Chamontin, B, Rousseau, H, Le Jeune, S, Lopez-Sublet, M, Mourad, JJ, Bellmann, L, Esnault, V, Ferrari, E, and Chatellier, G.
Published: 2019
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11. Empagliflozin, Health Status, and Quality of Life in Patients With Heart Failure and Preserved Ejection Fraction: The EMPEROR-Preserved Trial

Author: Butler, J, Filippatos, G, Jamal Siddiqi, T, Brueckmann, M, Bohm, M, Chopra, V, Pedro Ferreira, J, Januzzi, J, Kaul, S, Pina, I, Ponikowski, P, Shah, S, Senni, M, Vedin, O, Verma, S, Peil, B, Pocock, S, Zannad, F, Packer, M, Anker, S, Butler J., Filippatos G., Jamal Siddiqi T., Brueckmann M., Bohm M., Chopra V. K., Pedro Ferreira J., Januzzi J. L., Kaul S., Pina I. L., Ponikowski P., Shah S. J., Senni M., Vedin O., Verma S., Peil B., Pocock S. J., Zannad F., Packer M., Anker S. D., Butler, J, Filippatos, G, Jamal Siddiqi, T, Brueckmann, M, Bohm, M, Chopra, V, Pedro Ferreira, J, Januzzi, J, Kaul, S, Pina, I, Ponikowski, P, Shah, S, Senni, M, Vedin, O, Verma, S, Peil, B, Pocock, S, Zannad, F, Packer, M, Anker, S, Butler J., Filippatos G., Jamal Siddiqi T., Brueckmann M., Bohm M., Chopra V. K., Pedro Ferreira J., Januzzi J. L., Kaul S., Pina I. L., Ponikowski P., Shah S. J., Senni M., Vedin O., Verma S., Peil B., Pocock S. J., Zannad F., Packer M., and Anker S. D.
Abstract: Background: Patients with heart failure with preserved ejection fraction have significant impairment in health-related quality of life. In the EMPEROR-Preserved trial (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction), we evaluated the efficacy of empagliflozin on health-related quality of life in patients with heart failure with preserved ejection fraction and whether the clinical benefit observed with empagliflozin varies according to baseline health status. Methods: Health-related quality of life was measured with the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline and 12, 32, and 52 weeks. Patients were divided by baseline KCCQ Clinical Summary Score (CSS) tertiles, and the effect of empagliflozin on outcomes was examined. The effect of empagliflozin on KCCQ-CSS, Total Symptom Score, and Overall Summary Score was evaluated. Responder analyses were performed to compare the odds of improvement and deterioration in KCCQ related to treatment with empagliflozin. Results: The effect of empagliflozin on reducing the risk of time to cardiovascular death or heart failure hospitalization was consistent across baseline KCCQ-CSS tertiles (hazard ratio, 0.83 [95% CI, 0.69-1.00], 0.70 [95% CI, 0.55-0.88], and 0.82 [95% CI, 0.62-1.08] for scores <62.5, 62.5-83.3, and ≥83.3, respectively; P trend=0.77). Similar results were seen for total heart failure hospitalizations. Patients treated with empagliflozin had significant improvement in KCCQ-CSS versus placebo (+1.03, +1.24, and +1.50 at 12, 32, and 52 weeks, respectively; P<0.01); similar results were seen for Total Symptom Score and Overall Summary Score. At 12 weeks, patients on empagliflozin had higher odds of improvement ≥5 points (odds ratio, 1.23 [95% CI, 1.10-1.37]), ≥10 points (odds ratio, 1.15 [95% CI, 1.03-1.27]), and ≥15 points (odds ratio, 1.13 [95% CI, 1.02-1.26]) and lower odds of deterioration ≥5 points in KCCQ-CSS (odds ratio, 0.85 [95% CI, 0.7
Published: 2022

12. Angiotensin–neprilysin inhibition and renal outcomes across the spectrum of ejection fraction in heart failure

Author: Mc Causland, F, Lefkowitz, M, Claggett, B, Packer, M, Senni, M, Gori, M, Jhund, P, Mcgrath, M, Rouleau, J, Shi, V, Swedberg, K, Vaduganathan, M, Zannad, F, Pfeffer, M, Zile, M, Mcmurray, J, Solomon, S, Mc Causland F. R., Lefkowitz M. P., Claggett B., Packer M., Senni M., Gori M., Jhund P. S., McGrath M. M., Rouleau J. L., Shi V., Swedberg K., Vaduganathan M., Zannad F., Pfeffer M. A., Zile M., McMurray J. J. V., Solomon S. D., Mc Causland, F, Lefkowitz, M, Claggett, B, Packer, M, Senni, M, Gori, M, Jhund, P, Mcgrath, M, Rouleau, J, Shi, V, Swedberg, K, Vaduganathan, M, Zannad, F, Pfeffer, M, Zile, M, Mcmurray, J, Solomon, S, Mc Causland F. R., Lefkowitz M. P., Claggett B., Packer M., Senni M., Gori M., Jhund P. S., McGrath M. M., Rouleau J. L., Shi V., Swedberg K., Vaduganathan M., Zannad F., Pfeffer M. A., Zile M., McMurray J. J. V., and Solomon S. D.
Abstract: Aims: Patients with heart failure are at higher risk of progression to end-stage renal disease (ESRD), regardless of ejection fraction (EF). We assessed the renal effects of angiotensin–neprilysin inhibition in a pooled analysis of 13 195 patients with heart failure with reduced and preserved EF. Methods and results: We combined data from PARADIGM-HF (EF ≤40%; n = 8399) and PARAGON-HF (EF ≥45%; n = 4796) in a pre-specified pooled analysis. We assessed the effect of treatment (sacubitril/valsartan vs. enalapril or valsartan) on a composite of either ≥50% reduction in estimated glomerular filtration rate (eGFR), ESRD, or death from renal causes, in addition to changes in eGFR slope. We assessed whether baseline renal function or EF modified the effect of therapy on renal outcomes. At randomization, eGFR was 68 ± 20 ml/min/1.73 m2 in PARADIGM-HF and 63 ± 19 ml/min/1.73 m2 in PARAGON-HF. The composite renal outcome occurred in 70 of 6594 patients (1.1%) in the sacubitril/valsartan group and in 123 of 6601 patients (1.9%) in the valsartan or enalapril group (hazard ratio 0.56, 95% confidence interval [CI] 0.42–0.75; p < 0.001). The mean eGFR change was −1.8 (95% CI −1.9 to −1.7) ml/min/1.73 m2/year for the sacubitril/valsartan group, compared with −2.4 (95% CI −2.5 to −2.2) ml/min/1.73 m2/year for the valsartan or enalapril group. The treatment effect on the composite renal endpoint was not modified by categories of baseline eGFR (p-interaction = 0.64), but was most pronounced in those with baseline EF between 30% and 60% (p-interaction = 0.001). Conclusions: In patients with heart failure, sacubitril/valsartan reduced the risk of serious adverse renal outcomes and slowed decline in eGFR, compared with valsartan or enalapril, independent of baseline renal function.
Published: 2022

13. Unsupervised clustering to differentiate rheumatoid arthritis patients based on proteomic signatures

Author: Ferreira, MB, primary, Kobayashi, M, additional, Costa, RQ, additional, Fonseca, T, additional, Brandão, M, additional, Oliveira, JC, additional, Marinho, A, additional, Cyrne Carvalho, H, additional, Rodrigues, P, additional, Zannad, F, additional, Rossignol, P, additional, Barros, AS, additional, and Ferreira, JP, additional
Published: 2023
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14. Neural modulation for hypertension and heart failure

Author: Smith, S., Rossignol, P., Willis, S., Zannad, F., Mentz, R., Pocock, S., Bisognano, J., Nadim, Y., Geller, N., Ruble, S., and Linde, C.
Published: 2016
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15. Review of heart failure treatment in type 2 diabetes patients: It's at least as effective as in non-diabetic patients!

Author: Girerd, N., Zannad, F., and Rossignol, P.
Published: 2015
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16. Increased visit-to-visit blood pressure variability is associated with worse cardiovascular outcomes in low ejection fraction heart failure patients: Insights from the HEAAL study

Author: Rossignol, P., Girerd, N., Gregory, D., Massaro, J., Konstam, M.A., and Zannad, F.
Published: 2015
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17. Unsupervised clustering to differentiate rheumatoid arthritis patients based on proteomic signatures

Author: Ferreira, MB, Kobayashi, M, Costa, RQ, Fonseca, T, Brandão, M, Oliveira, JC, Marinho, A, Carvalho, H Cyrne, Rodrigues, P, Zannad, F, Rossignol, P, Barros, AS, and Ferreira, JP
Abstract: Patients with rheumatoid arthritis (RA) have different presentations and prognoses. Cluster analysis based on proteomic signatures creates independent phenogroups of patients with different pathophysiological backgrounds. We aimed to identify distinct pathophysiological clusters of RA patients based on circulating proteomic biomarkers. This was a cohort study including 399 RA patients. Clustering was performed on 94 circulating proteins (92 CVDII Olink®, high-sensitivity troponin T, and C-reactive protein). Unsupervised clustering was performed using a partitioning cluster algorithm. The clustering algorithm identified two distinct clusters: cluster 1 (n = 223) and cluster 2 (n = 176). Compared with cluster 1, cluster 2 included older patients with a higher burden of comorbidities (cardiovascular and RA related), more erosive and longer RA duration, more dyspnoea and fatigue, walking a shorter distance in the Six-Minute Walk Test, with more severe diastolic dysfunction, and a 4.5-fold higher risk of death or hospitalization for cardiovascular reasons. Tumour necrosis factor (TNF) receptor superfamily-related pathways were mainly responsible for the model’s discriminative ability. Using unsupervised cluster analysis based on proteomic phenotypes, we identified two clusters of RA patients with distinct biomarkers profiles, clinical characteristics, and different outcomes that could reflect different pathophysiological backgrounds. TNF receptor superfamily-related proteins may be used to distinguish subgroups.
Published: 2023
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18. NT-proBNP and stem cell factor plasma concentrations are independently associated with cardiovascular outcomes in end-stage renal disease hemodialysis patients

Author: Rossignol, P, primary, Duarte, K, additional, Bresso, E, additional, A, Åsberg, additional, Devignes, M D, additional, Eriksson, N, additional, Girerd, N, additional, Glerup, R, additional, Jardine, A G, additional, Holdaas, H, additional, Lamiral, Z, additional, Leroy, C, additional, Massy, Z, additional, März, W, additional, Krämer, B, additional, Wu, P H, additional, Schmieder, R, additional, Soveri, I, additional, Christensen, J H, additional, Svensson, M, additional, Zannad, F, additional, and Fellström, B, additional
Published: 2022
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19. Association of heart rate with heart failure outcomes and the effects of empagliflozin in patients with preserved ejection fraction – EMPEROR-Preserved trial

Author: Boehm, M, primary, Anker, S D, additional, Mahfoud, F, additional, Filippatos, G, additional, Ferreira, J P, additional, Pocock, S J, additional, Brueckmann, M, additional, Linetzky, B, additional, Schueler, E, additional, Wanner, C, additional, Zannad, F, additional, Packer, M, additional, and Butler, J, additional
Published: 2022
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20. Incident hyperkalemia may be an independent therapeutic target in low ejection fraction heart failure patients: Insights from the HEAAL study

Author: Rossignol, P., Dobre, D., Gregory, D., Massaro, J., Kiernan, M., Konstam, M.A., and Zannad, F.
Published: 2014
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21. Hypertension and heart failure with preserved ejection fraction: Position paper by the European Society ofHypertension

Author: Kasiakogias, A, Rosei, E, Camafort, M, Ehret, G, Faconti, L, Ferreira, J, Brguljan, J, Januszewicz, A, Kahan, T, Manolis, A, Tsioufis, K, Weber, T, Lueder, T, Smiseth, O, Wachtell, K, Kjeldsen, S, Zannad, F, Mancia, G, Kreutz, R, Kasiakogias A., Rosei E. A., Camafort M., Ehret G., Faconti L., Ferreira J. P., Brguljan J., Januszewicz A., Kahan T., Manolis A., Tsioufis K., Weber T., Lueder T. G. v., Smiseth O. A., Wachtell K., Kjeldsen S. E., Zannad F., Mancia G., Kreutz R., Kasiakogias, A, Rosei, E, Camafort, M, Ehret, G, Faconti, L, Ferreira, J, Brguljan, J, Januszewicz, A, Kahan, T, Manolis, A, Tsioufis, K, Weber, T, Lueder, T, Smiseth, O, Wachtell, K, Kjeldsen, S, Zannad, F, Mancia, G, Kreutz, R, Kasiakogias A., Rosei E. A., Camafort M., Ehret G., Faconti L., Ferreira J. P., Brguljan J., Januszewicz A., Kahan T., Manolis A., Tsioufis K., Weber T., Lueder T. G. v., Smiseth O. A., Wachtell K., Kjeldsen S. E., Zannad F., Mancia G., and Kreutz R.
Abstract: Hypertension constitutes a major risk factor for heart failure with preserved ejection fraction (HFpEF). HFpEF is a prevalent clinical syndrome with increased cardiovascular morbidity and mortality. Specific guideline-directed medical therapy (GDMT) for HFpEF is not established due to lack of positive outcome data from randomized controlled trials (RCTs) and limitations of available studies. Although available evidence is limited, control of blood pressure (BP) is widely regarded as central to the prevention and clinical care in HFpEF. Thus, in current guidelines including the 2018 European Society of Cardiology (ESC) and European Society of Hypertension (ESH) Guidelines, blockade of the renin-angiotensin system (RAS) with either angiotensinconverting enzyme inhibitors or angiotensin receptor blockers provides the backbone of BP-lowering therapy in hypertensive patients. Although superiority of RAS blockers has not been clearly shown in dedicated RCTs designed for HFpEF, we propose that this core drug treatment strategy is also applicable for hypertensive patients with HFpEF with the addition of some modifications. The latter apply to the use of spironolactone apart from the treatment of resistant hypertension and the use of the angiotensin receptor neprilysin inhibitor. In addition, novel agents such as sodium-glucose co-transporter-2 inhibitors, currently already indicated for high-risk patients with diabetes to reduce heart failure hospitalizations, and finerenone represent promising therapies and results from ongoing RCTs are eagerly awaited. The development of an effective and practical classification of HFpEF phenotypes and GDMT through dedicated high-quality RCTs are major unmet needs in hypertension research and calls for action.
Published: 2021

22. Integrating High-Sensitivity Troponin T and Sacubitril/Valsartan Treatment in HFpEF: The PARAGON-HF Trial

Author: Gori, M, Senni, M, Claggett, B, Liu, J, Maggioni, A, Zile, M, Prescott, M, Van Veldhuisen, D, Zannad, F, Pieske, B, Lam, C, Rouleau, J, Jhund, P, Packer, M, Pfeffer, M, Lefkowitz, M, Shi, V, Mcmurray, J, Solomon, S, Gori M, Senni M, Claggett B, Liu J, Maggioni AP, Zile M, Prescott MF, Van Veldhuisen DJ, Zannad F, Pieske B, Lam CSP, Rouleau J, Jhund P, Packer M, Pfeffer MA, Lefkowitz M, Shi V, McMurray JJV, Solomon SD, Gori, M, Senni, M, Claggett, B, Liu, J, Maggioni, A, Zile, M, Prescott, M, Van Veldhuisen, D, Zannad, F, Pieske, B, Lam, C, Rouleau, J, Jhund, P, Packer, M, Pfeffer, M, Lefkowitz, M, Shi, V, Mcmurray, J, Solomon, S, Gori M, Senni M, Claggett B, Liu J, Maggioni AP, Zile M, Prescott MF, Van Veldhuisen DJ, Zannad F, Pieske B, Lam CSP, Rouleau J, Jhund P, Packer M, Pfeffer MA, Lefkowitz M, Shi V, McMurray JJV, and Solomon SD
Abstract: Objectives: This study examined the relationship among high-sensitivity troponin-T (hs-TnT), outcomes, and treatment with sacubitril/valsartan in patients with heart failure (HF) and preserved ejection fraction (HFpEF). Background: hs-TnT is a marker of myocardial injury in HF. Methods: The PARAGON-HF trial randomized 4,796 patients with HFpEF to sacubitril/valsartan or valsartan. We compared the risk of the composite outcome of cardiovascular death (CVD) and total HF hospitalization (HHF) according to hs-TnT. We also assessed the effect of allocated treatment on hs-TnT. Results: hs-TnT was available in 1,141 patients (24%) at run-in (median value: 17 ng/L) and 1,260 (26%) at randomization, with 58.3% having hs-TnT >14 ng/L (upper limit of normal). During a median follow-up of 34 months, there were 393 outcome events (82 CVD, 311 HHF). Adjusting for demographics, comorbidities, left ventricular ejection fraction (LVEF), and N-terminal pro B-type natriuretic peptide (NT-proBNP), log-hs-TnT at randomization was an independent predictor of the composite outcome (HR: 1.38; 95% CI: 1.19-1.59; P < 0.001). Compared with valsartan, sacubitril/valsartan significantly reduced hs-TnT by 9% at week 16 (P < 0.001). Patients whose hs-TnT decreased from randomization to 16 weeks to at or below the median value of 17 ng/L subsequently had a lower risk of CVD/HHF compared with those with persistently elevated hs-TnT (P = 0.046). Patients with higher baseline hs-TnT (>17 ng/L) appeared to have a greater benefit from sacubitril/valsartan treatment when accounting for other potential effect modifiers (P interaction = 0.07). Conclusions: Higher baseline hs-TnT was associated with increased risk of CVD/HHF, whereas hs-TnT decrease at 16 weeks led to lower subsequent risk of CVD/HHF compared with those who had persistently elevated values. Sacubitril/valsartan significantly reduced hs-TnT compared with valsartan. hs-TnT may be helpful in identifying patients with HFpEF who are
Published: 2021

23. Empagliflozin in heart failure with a preserved ejection fraction

Author: Anker, S, Butler, J, Filippatos, G, Ferreira, J, Bocchi, E, Böhm, M, Brunner-La Rocca, H, Choi, D, Chopra, V, Chuquiure-Valenzuela, E, Giannetti, N, Gomez-Mesa, J, Janssens, S, Januzzi, J, Gonzalez-Juanatey, J, Merkely, B, Nicholls, S, Perrone, S, Piña, I, Ponikowski, P, Senni, M, Sim, D, Spinar, J, Squire, I, Taddei, S, Tsutsui, H, Verma, S, Vinereanu, D, Zhang, J, Carson, P, Lam, C, Marx, N, Zeller, C, Sattar, N, Jamal, W, Schnaidt, S, Schnee, J, Brueckmann, M, Pocock, S, Zannad, F, Packer, M, EMPEROR-Preserved Trial, I, Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Böhm M, Brunner-La Rocca HP, Choi DJ, Chopra V, Chuquiure-Valenzuela E, Giannetti N, Gomez-Mesa JE, Janssens S, Januzzi JL, Gonzalez-Juanatey JR, Merkely B, Nicholls SJ, Perrone SV, Piña IL, Ponikowski P, Senni M, Sim D, Spinar J, Squire I, Taddei S, Tsutsui H, Verma S, Vinereanu D, Zhang J, Carson P, Lam CSP, Marx N, Zeller C, Sattar N, Jamal W, Schnaidt S, Schnee JM, Brueckmann M, Pocock SJ, Zannad F, Packer M, EMPEROR-Preserved Trial Investigators, Anker, S, Butler, J, Filippatos, G, Ferreira, J, Bocchi, E, Böhm, M, Brunner-La Rocca, H, Choi, D, Chopra, V, Chuquiure-Valenzuela, E, Giannetti, N, Gomez-Mesa, J, Janssens, S, Januzzi, J, Gonzalez-Juanatey, J, Merkely, B, Nicholls, S, Perrone, S, Piña, I, Ponikowski, P, Senni, M, Sim, D, Spinar, J, Squire, I, Taddei, S, Tsutsui, H, Verma, S, Vinereanu, D, Zhang, J, Carson, P, Lam, C, Marx, N, Zeller, C, Sattar, N, Jamal, W, Schnaidt, S, Schnee, J, Brueckmann, M, Pocock, S, Zannad, F, Packer, M, EMPEROR-Preserved Trial, I, Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Böhm M, Brunner-La Rocca HP, Choi DJ, Chopra V, Chuquiure-Valenzuela E, Giannetti N, Gomez-Mesa JE, Janssens S, Januzzi JL, Gonzalez-Juanatey JR, Merkely B, Nicholls SJ, Perrone SV, Piña IL, Ponikowski P, Senni M, Sim D, Spinar J, Squire I, Taddei S, Tsutsui H, Verma S, Vinereanu D, Zhang J, Carson P, Lam CSP, Marx N, Zeller C, Sattar N, Jamal W, Schnaidt S, Schnee JM, Brueckmann M, Pocock SJ, Zannad F, Packer M, and EMPEROR-Preserved Trial Investigators
Abstract: BACKGROUND Sodium–glucose cotransporter 2 inhibitors reduce the risk of hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, but their effects in patients with heart failure and a preserved ejection fraction are uncertain. METHODS In this double-blind trial, we randomly assigned 5988 patients with class II–IV heart failure and an ejection fraction of more than 40% to receive empagliflozin (10 mg once daily) or placebo, in addition to usual therapy. The primary outcome was a composite of cardiovascular death or hospitalization for heart failure. RESULTS Over a median of 26.2 months, a primary outcome event occurred in 415 of 2997 patients (13.8%) in the empagliflozin group and in 511 of 2991 patients (17.1%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.69 to 0.90; P<0.001). This effect was mainly related to a lower risk of hospitalization for heart failure in the empagliflozin group. The effects of empagliflozin appeared consistent in patients with or without diabetes. The total number of hospitalizations for heart failure was lower in the empagliflozin group than in the placebo group (407 with empagliflozin and 541 with placebo; hazard ratio, 0.73; 95% CI, 0.61 to 0.88; P<0.001). Uncomplicated genital and urinary tract infections and hypotension were reported more frequently with empagliflozin. CONCLUSIONS Empagliflozin reduced the combined risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a preserved ejection fraction, regardless of the presence or absence of diabetes.
Published: 2021

24. NON-ADHERENCE TO ANTIHYPERTENSIVE TREATMENT IS A MAJOR DETERMINANT OF THE CLINIC-AMBULATORY BP DIFFERENCE IN PATIENTS WITH RESISTANT HYPERTENSION

Author: Hamdidouche, I., Pereira, H., Gosse, P., Bobrie, G., Courand, P.-Y., Delsart, P., Mounier-Vehier, C., Lantelme, P., Denolle, T., Dourmap, C., Halimi, J.-M., Girerd, X., Rossignol, P., Zannad, F., Ormezzanno, O., Vaisse, B., Herpin, D., Ribstein, J., Mourad, J.J., Ferrari, E., Chatellier, G., Jullien, V., and Azizi, M.
Published: 2018
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25. High cholesterol absorption is associated with increased cardiovascular risk in hemodialysis patients: Insights from the AURORA study

Author: Silbernagel, G., primary, Duarte, K., additional, Sadiku, S., additional, Fauler, G., additional, Maerz, W., additional, Schmieder, R.E., additional, Jardine, A.G., additional, Massy, Z.A., additional, Girerd, N., additional, Fellström, B., additional, Scharnagl, H., additional, and Zannad, F., additional
Published: 2022
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26. Angiotensin-neprilysin inhibition and renal outcomes in heart failure with preserved ejection fraction

Author: Mc Causland, F, Lefkowitz, M, Claggett, B, Anavekar, N, Senni, M, Gori, M, Jhund, P, Mcgrath, M, Packer, M, Shi, V, Van Veldhuisen, D, Zannad, F, Comin-Colet, J, Pfeffer, M, Mcmurray, J, Solomon, S, Mc Causland FR, Lefkowitz MP, Claggett B, Anavekar NS, Senni M, Gori M, Jhund PS, McGrath MM, Packer M, Shi V, Van Veldhuisen DJ, Zannad F, Comin-Colet J, Pfeffer MA, McMurray JJV, Solomon SD, Mc Causland, F, Lefkowitz, M, Claggett, B, Anavekar, N, Senni, M, Gori, M, Jhund, P, Mcgrath, M, Packer, M, Shi, V, Van Veldhuisen, D, Zannad, F, Comin-Colet, J, Pfeffer, M, Mcmurray, J, Solomon, S, Mc Causland FR, Lefkowitz MP, Claggett B, Anavekar NS, Senni M, Gori M, Jhund PS, McGrath MM, Packer M, Shi V, Van Veldhuisen DJ, Zannad F, Comin-Colet J, Pfeffer MA, McMurray JJV, and Solomon SD
Abstract: BACKGROUND: In patients with heart failure, chronic kidney disease is common and associated with a higher risk of renal events than in patients without chronic kidney disease. We assessed the renal effects of angiotensin/neprilysin inhibition in patients who have heart failure with preserved ejection fraction enrolled in the PARAGON-HF trial (Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction). METHODS: In this randomized, double-blind, event-driven trial, we assigned 4822 patients who had heart failure with preserved ejection fraction to receive sacubitril/valsartan (n=2419) or valsartan (n=2403). Herein, we present the results of the prespecified renal composite outcome (time to first occurrence of either: ≥50% reduction in estimated glomerular filtration rate (eGFR), end-stage renal disease, or death from renal causes), the individual components of this composite, and the influence of therapy on eGFR slope. RESULTS: At randomization, eGFR was 63±19 mL·min–1·1.73 m–2. At study closure, the composite renal outcome occurred in 33 patients (1.4%) assigned to sacubitril/valsartan and 64 patients (2.7%) assigned to valsartan (hazard ratio, 0.50 [95% CI, 0.33–0.77]; P=0.001). The treatment effect on the composite renal end point did not differ according to the baseline eGFR (<60 versus ≥60 mL·min–1·1.73 m–2 (Pinteraction=0.92). The decline in eGFR was less for sacubitril/valsartan than for valsartan (–2.0 [95% CI, –2.2 to –1.9] versus –2.7 [95% CI, –2.8 to –2.5] mL·min–1·1.73 m–2 per year). CONCLUSIONS: In patients with heart failure with preserved ejection fraction, sacubitril/valsartan reduced the risk of renal events, and slowed decline in eGFR, in comparison with valsartan.
Published: 2020

27. Cardiovascular and renal outcomes with empagliflozin in heart failure

Author: Packer, M, Anker, S, Butler, J, Filippatos, G, Pocock, S, Carson, P, Januzzi, J, Verma, S, Tsutsui, H, Brueckmann, M, Jamal, W, Kimura, K, Schnee, J, Zeller, C, Cotton, D, Bocchi, E, Böhm, M, Choi, D, Chopra, V, Chuquiure, E, Giannetti, N, Janssens, S, Zhang, J, Gonzalez Juanatey, J, Kaul, S, Brunner-La Rocca, H, Merkely, B, Nicholls, S, Perrone, S, Pina, I, Ponikowski, P, Sattar, N, Senni, M, Seronde, M, Spinar, J, Squire, I, Taddei, S, Wanner, C, Zannad, F, Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, Januzzi J, Verma S, Tsutsui H, Brueckmann M, Jamal W, Kimura K, Schnee J, Zeller C, Cotton D, Bocchi E, Böhm M, Choi DJ, Chopra V, Chuquiure E, Giannetti N, Janssens S, Zhang J, Gonzalez Juanatey JR, Kaul S, Brunner-La Rocca HP, Merkely B, Nicholls SJ, Perrone S, Pina I, Ponikowski P, Sattar N, Senni M, Seronde MF, Spinar J, Squire I, Taddei S, Wanner C, Zannad F, Packer, M, Anker, S, Butler, J, Filippatos, G, Pocock, S, Carson, P, Januzzi, J, Verma, S, Tsutsui, H, Brueckmann, M, Jamal, W, Kimura, K, Schnee, J, Zeller, C, Cotton, D, Bocchi, E, Böhm, M, Choi, D, Chopra, V, Chuquiure, E, Giannetti, N, Janssens, S, Zhang, J, Gonzalez Juanatey, J, Kaul, S, Brunner-La Rocca, H, Merkely, B, Nicholls, S, Perrone, S, Pina, I, Ponikowski, P, Sattar, N, Senni, M, Seronde, M, Spinar, J, Squire, I, Taddei, S, Wanner, C, Zannad, F, Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, Januzzi J, Verma S, Tsutsui H, Brueckmann M, Jamal W, Kimura K, Schnee J, Zeller C, Cotton D, Bocchi E, Böhm M, Choi DJ, Chopra V, Chuquiure E, Giannetti N, Janssens S, Zhang J, Gonzalez Juanatey JR, Kaul S, Brunner-La Rocca HP, Merkely B, Nicholls SJ, Perrone S, Pina I, Ponikowski P, Sattar N, Senni M, Seronde MF, Spinar J, Squire I, Taddei S, Wanner C, and Zannad F
Abstract: BACKGROUND Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure in patients regardless of the presence or absence of diabetes. More evidence is needed regarding the effects of these drugs in patients across the broad spectrum of heart failure, including those with a markedly reduced ejection fraction. METHODS In this double-blind trial, we randomly assigned 3730 patients with class II, III, or IV heart failure and an ejection fraction of 40% or less to receive empagliflozin (10 mg once daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of cardiovascular death or hospitalization for worsening heart failure. RESULTS During a median of 16 months, a primary outcome event occurred in 361 of 1863 patients (19.4%) in the empagliflozin group and in 462 of 1867 patients (24.7%) in the placebo group (hazard ratio for cardiovascular death or hospitalization for heart failure, 0.75; 95% confidence interval [CI], 0.65 to 0.86; P<0.001). The effect of empagliflozin on the primary outcome was consistent in patients regardless of the presence or absence of diabetes. The total number of hospitalizations for heart failure was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.70; 95% CI, 0.58 to 0.85; P<0.001). The annual rate of decline in the estimated glomerular filtration rate was slower in the empagliflozin group than in the placebo group (-0.55 vs. -2.28 ml per minute per 1.73 m2 of body-surface area per year, P<0.001), and empagliflozin-treated patients had a lower risk of serious renal outcomes. Uncomplicated genital tract infection was reported more frequently with empagliflozin. CONCLUSIONS Among patients receiving recommended therapy for heart failure, those in the empagliflozin group had a lower risk of cardiovascular death or hospitalization for heart failure than those in the placebo group, regardless of the presence or absence of diabetes.
Published: 2020

28. Baseline characteristics of patients with heart failure with preserved ejection fraction in the EMPEROR-Preserved trial

Author: Anker, S, Butler, J, Filippatos, G, Shahzeb Khan, M, Ferreira, J, Bocchi, E, Böhm, M, Brunner-La Rocca, H, Choi, D, Chopra, V, Chuquiure, E, Giannetti, N, Gomez-Mesa, J, Janssens, S, Januzzi, J, Gonzalez-Juanatey, J, Merkely, B, Nicholls, S, Perrone, S, Piña, I, Ponikowski, P, Senni, M, Seronde, M, Sim, D, Spinar, J, Squire, I, Taddei, S, Tsutsui, H, Verma, S, Vinereanu, D, Zhang, J, Jamal, W, Schnaidt, S, Schnee, J, Brueckmann, M, Pocock, S, Zannad, F, Packer, M, EMPEROR-Preserved Trial Committees and, I, Anker SD, Butler J, Filippatos G, Shahzeb Khan M, Ferreira JP, Bocchi E, Böhm M, Brunner-La Rocca HP, Choi DJ, Chopra V, Chuquiure E, Giannetti N, Gomez-Mesa JE, Janssens S, Januzzi JL, Gonzalez-Juanatey JR, Merkely B, Nicholls SJ, Perrone SV, Piña IL, Ponikowski P, Senni M, Seronde MF, Sim D, Spinar J, Squire I, Taddei S, Tsutsui H, Verma S, Vinereanu D, Zhang J, Jamal W, Schnaidt S, Schnee JM, Brueckmann M, Pocock SJ, Zannad F, Packer M, EMPEROR-Preserved Trial Committees and Investigators, Anker, S, Butler, J, Filippatos, G, Shahzeb Khan, M, Ferreira, J, Bocchi, E, Böhm, M, Brunner-La Rocca, H, Choi, D, Chopra, V, Chuquiure, E, Giannetti, N, Gomez-Mesa, J, Janssens, S, Januzzi, J, Gonzalez-Juanatey, J, Merkely, B, Nicholls, S, Perrone, S, Piña, I, Ponikowski, P, Senni, M, Seronde, M, Sim, D, Spinar, J, Squire, I, Taddei, S, Tsutsui, H, Verma, S, Vinereanu, D, Zhang, J, Jamal, W, Schnaidt, S, Schnee, J, Brueckmann, M, Pocock, S, Zannad, F, Packer, M, EMPEROR-Preserved Trial Committees and, I, Anker SD, Butler J, Filippatos G, Shahzeb Khan M, Ferreira JP, Bocchi E, Böhm M, Brunner-La Rocca HP, Choi DJ, Chopra V, Chuquiure E, Giannetti N, Gomez-Mesa JE, Janssens S, Januzzi JL, Gonzalez-Juanatey JR, Merkely B, Nicholls SJ, Perrone SV, Piña IL, Ponikowski P, Senni M, Seronde MF, Sim D, Spinar J, Squire I, Taddei S, Tsutsui H, Verma S, Vinereanu D, Zhang J, Jamal W, Schnaidt S, Schnee JM, Brueckmann M, Pocock SJ, Zannad F, Packer M, and EMPEROR-Preserved Trial Committees and Investigators
Abstract: Aims: EMPEROR-Preserved is an ongoing trial evaluating the effect of empagliflozin in patients with heart failure with preserved ejection fraction (HFpEF). This report describes the baseline characteristics of the EMPEROR-Preserved cohort and compares them with patients enrolled in prior HFpEF trials. Methods and results: EMPEROR-Preserved is a phase III randomized, international, double-blind, parallel-group, placebo-controlled trial in which 5988 symptomatic HFpEF patients [left ventricular ejection fraction (LVEF) >40%] with and without type 2 diabetes mellitus (T2DM) have been enrolled. Patients were required to have elevated N-terminal pro B-type. natriuretic peptide (NT-proBNP) concentrations (i.e. >300 pg/mL in patients without and >900 pg/mL in patients with atrial fibrillation) along with evidence of structural changes in the heart or documented history of heart failure hospitalization. Among patients enrolled from various regions (45% Europe, 11% Asia, 25% Latin America, 12% North America), the mean age was 72 ± 9 years, 45% were women. Almost all patients had New York Heart Association class II or III symptoms (99.6%), and 23% had prior heart failure hospitalization within 12 months. Thirty-three percent of the patients had baseline LVEF of 41–50%. The mean LVEF (54 ± 9%) was slightly lower while the median NT-proBNP [974 (499–1731) pg/mL] was higher compared with previous HFpEF trials. Presence of comorbidities such as diabetes (49%) and chronic kidney disease (50%) were common. The majority of the patients were on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor–neprilysin inhibitors (80%) and beta-blockers (86%), and 37% of patients were on mineralocorticoid receptor antagonists. Conclusion: When compared with prior trials in HFpEF, the EMPEROR-Preserved cohort has a somewhat higher burden of comorbidities, lower LVEF, higher median NT-proBNP and greater use of mineralocorticoid receptor antagonists a
Published: 2020

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

Author: Rossignol, P, Duarte, K, Bresso, E, A, Åsberg, Devignes, M D, Eriksson, N, Girerd, N, Glerup, R, Jardine, A G, Holdaas, H, Lamiral, Z, Leroy, C, Massy, Z, März, W, Krämer, B, Wu, Ping-Hsun, Schmieder, R, Soveri, Inga, Christensen, J H, Svensson, M, Zannad, F, Fellström, Bengt, Rossignol, P, Duarte, K, Bresso, E, A, Åsberg, Devignes, M D, Eriksson, N, Girerd, N, Glerup, R, Jardine, A G, Holdaas, H, Lamiral, Z, Leroy, C, Massy, Z, März, W, Krämer, B, Wu, Ping-Hsun, Schmieder, R, Soveri, Inga, Christensen, J H, Svensson, M, Zannad, F, and Fellström, Bengt
Abstract: Aimas: End-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 Results: The 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. Conclusions: Our 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
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30. Weak association between genetic markers of hyperuricemia and cardiorenal outcomes: insights from the STANISLAS study cohort with a 20-year follow-up

Author: Kanbay, Mehmet (ORCID 0000-0002-1297-0675 & YÖK ID 110580), Xhaard, C.; Le Floch, E.; Dandine-Roulland, C.; Girerd, N.; Ferreira, J.P.; Boivin, J.M.; Wagner, S.; Bacq Daian, D.; Deleuze, J.F.; Zannad, F.; Rossignol, P., School of Medicine, Kanbay, Mehmet (ORCID 0000-0002-1297-0675 & YÖK ID 110580), Xhaard, C.; Le Floch, E.; Dandine-Roulland, C.; Girerd, N.; Ferreira, J.P.; Boivin, J.M.; Wagner, S.; Bacq Daian, D.; Deleuze, J.F.; Zannad, F.; Rossignol, P., and School of Medicine
Abstract: Background: Hyperuricemia is associated with poor cardiovascular outcomes, although it is uncertain whether this relationship is causal in nature. This study aimed to: (1) assess the heritability of serum uric acid (SUA) levels, (2) conduct a genome-wide association study on SUA levels, and (3) investigate the association between certain single-nucleotide polymorphisms and target organ damage. Methods and results: the STANISLAS (Suivi Temporaire Annuel Non-Invasif de la Sante des Lorrains Assures Sociaux) study cohort is a single-center longitudinal cohort recruited between 1993 and 1995 (visit 1), with a last visit (visit 4 [V4]) performed approximate to 20 years apart. Serum lipid profile, SUA, urinary albumin/creatinine ratio, estimated glomerular filtration rate, 24-hour ambulatory blood pressure monitoring, transthoracic echocardiography, pulse wave velocity, and genotyping for each participant were assessed at V4. A total of 1573 participants were included at V4, among whom 1417 had available SUA data at visit 1. Genome-wide association study results highlighted multiple single-nucleotide polymorphisms on the SLC2A9 gene linked to SUA levels. Carriers of the most associated mutated SLC2A9 allele (rs16890979) had significantly lower SUA levels. Although SUA level at V4 was highly associated with diabetes, prediabetes, higher body mass index, CRP (C-reactive protein) levels, estimated glomerular filtration rate variation (visit 1-V4), carotid intima-media thickness, and pulse wave velocity, rs16890979 was only associated with higher carotid intima-media thickness. Conclusions: our findings demonstrate that rs16890979, a genetic determinant of SUA levels located on the SLC2A9 gene, is associated with carotid intima-media thickness despite significant associations between SUA levels and several clinical outcomes, thereby lending support to the hypothesis of a link between SUA and cardiovascular disease., Nancy Centre Hospitalier Regional Universitaire; French Ministry of Health; French National Research Agency (ANR); Contrat de Plan Etat?Lorraine and Fonds Européen de Développement Régional Lorraine; Programme Hospitalier de Recherche Clinique Inter regional 2013; Investissements d’Avenir; FIGHT?heart failure; French Plan d'Investissement d'Avenir project “Lorraine Université d’Excellence; European Union (EU); European Fibro?Targets Project; European HOMAGE project; 7th Framework Program; MEDIA project; FOCUS?MR; ERA?CVD EXPERT; Fondation de Recherche en Hypertension Artérielle
Published: 2022

31. [OP.8A.02] SHORT TELOMERES, BUT NOT TELOMERE ATTRITION RATES, ARE ASSOCIATED WITH CAROTID ATHEROSCLEROSIS

Author: Toupance, S., Kearney-Schwartz, A., Temmar, M., Lakomy, C., Labat, C., Rossignol, P., Zannad, F., Aviv, A., and Benetos, A.
Published: 2017
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32. Evaluation of the effect of sodium–glucose co‐transporter 2 inhibition with empagliflozin on morbidity and mortality of patients with chronic heart failure and a reduced ejection fraction: rationale for and design of the EMPEROR‐Reduced trial

Author: Packer M., Butler J., Filippatos G. S., Jamal W., Salsali A., Schnee J., Kimura K., Zeller C., George J., Brueckmann M., Anker S. D., Zannad F., Perrone S., Nicholls S., Janssens S., Bocchi E., Giannetti N., Verma S., Jian Z., Spinar J., Seronde M. -F., Bohm M., Merkely B., Chopra V., Senni M., Taddei S., Tsutsui H., Choi D. -J., Chuquiure E., La Rocca H. P. B., Ponikowski P., Juanatey J. R. G., Squire I., Januzzi J., Pina I., Pocock S. J., 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 M., Bernstein R., Cheung A., Green J., Kaul S., Ping C. L. S., Lip G., Marx N., McCullough P., Mehta C., Rosenstock J., Sattar N., Scirica B., Wanner C., Welty F. K., Parhofer K. G., Clayton T., Pedersen T. R., Lees K. R., Konstam M. A., Greenberg B., Palmer M., Packer, M, Butler, J, Filippatos, G, Jamal, W, Salsali, A, Schnee, J, Kimura, K, Zeller, C, George, J, Brueckmann, M, Anker, S, Zannad, F, Perrone, S, Nicholls, S, Janssens, S, Bocchi, E, Giannetti, N, Verma, S, Jian, Z, Spinar, J, Seronde, M, Bohm, M, Merkely, B, Chopra, V, Senni, M, Taddei, S, Tsutsui, H, Choi, D, Chuquiure, E, La Rocca, H, Ponikowski, P, Juanatey, J, Squire, I, Januzzi, J, Pina, I, Pocock, S, 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, M, Bernstein, R, Cheung, A, Green, J, Kaul, S, Ping, C, Lip, G, Marx, N, Mccullough, P, Mehta, C, Rosenstock, J, Sattar, N, Scirica, B, Wanner, C, Welty, F, Parhofer, K, Clayton, T, Pedersen, T, Lees, K, Konstam, M, Greenberg, B, Palmer, M, RS: Carim - H02 Cardiomyopathy, MUMC+: MA Med Staf Spec Cardiologie (9), Cardiologie, and RS: CARIM - R2.02 - Cardiomyopathy
Subjects: MECHANISM, Trial design, medicine.medical_specialty, Cardiac & Cardiovascular Systems, NA+/H+-EXCHANGER, Heart failure, Type 2 diabetes, 030204 cardiovascular system & hematology, Diabete, SGLT2 INHIBITORS, Reduced ejection fraction, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Glucosides, Internal medicine, Diabetes mellitus, Clinical endpoint, Empagliflozin, Humans, Medicine, Benzhydryl Compounds, Dapagliflozin, Sodium-Glucose Transporter 2 Inhibitors, Randomized Controlled Trials as Topic, RISK, Canagliflozin, OUTCOMES, Science & Technology, Ejection fraction, diabetes, business.industry, Diabetes, Stroke Volume, SGLT2 inhibitor, medicine.disease, chemistry, HOSPITALIZATION, Chronic Disease, Cardiovascular System & Cardiology, Cardiology, Cardiology and Cardiovascular Medicine, business, Life Sciences & Biomedicine, medicine.drug
Abstract: Drugs that inhibit the sodium-glucose co-transporter 2 (SGLT2) have been shown to reduce the risk of hospitalizations for heart failure in patients with type 2 diabetes. In populations that largely did not have heart failure at the time of enrolment, empagliflozin, canagliflozin and dapagliflozin decreased the risk of serious new-onset heart failure events by ≈30%. In addition, in the EMPA-REG OUTCOME trial, empagliflozin reduced the risk of both pump failure and sudden deaths, the two most common modes of death among patients with heart failure. In none of the three trials could the benefits of SGLT2 inhibitors on heart failure be explained by the actions of these drugs as diuretics or anti-hyperglycaemic agents. These observations raise the possibility that SGLT2 inhibitors could reduce morbidity and mortality in patients with established heart failure, including those without diabetes. The EMPEROR-Reduced trial is enrolling ≈3600 patients with heart failure and a reduced left ventricular ejection fraction (≤ 40%), half of whom are expected not to have diabetes. Patients are being randomized to placebo or empagliflozin 10 mg daily, which is added to all appropriate treatment with inhibitors of the renin-angiotensin system and neprilysin, beta-blockers and mineralocorticoid receptor antagonists. The primary endpoint is the time-to-first event analysis of the combined risk of cardiovascular death and hospitalization for heart failure, but the trial will also evaluate the effects of empagliflozin on renal function, cardiovascular death, all-cause mortality, and recurrent hospitalization events. By adjusting eligibility based on natriuretic peptide levels to the baseline ejection fraction, the trial will preferentially enrol high-risk patients. A large proportion of the participants is expected to have an ejection fraction
Published: 2019

33. Outcomes with empagliflozin in heart failure with preserved ejection fraction using DELIVER-like endpoint definitions

Author: Anker, S.D. Siddiqi, T.J. Filippatos, G. Zannad, F. Ferreira, J.P. Pocock, S.J. Brueckmann, M. Zeller, C. Packer, M. Butler, J.
Abstract: Aims: To report data from EMPEROR-Preserved according to prespecified endpoints of DELIVER. Methods and results: In order to assess the impact of DELIVER-like definition on EMPEROR-Preserved outcomes, the following differences were reconciled: (1) the primary outcome in DELIVER added urgent heart failure (HF) visits to cardiovascular death or HF hospitalizations; (2) the EMPEROR-Preserved trial did not require documentation of physical findings or laboratory tests for confirming a HF hospitalization and it included events of 12–24 h if intensification of treatment was not only oral diuretics; (3) DELIVER excluded undetermined causes of deaths from the primary endpoint; (4) the composite renal endpoint in DELIVER included a sustained ≥50% decline in estimated glomerular filtration rate and incorporated renal death; and (5) DELIVER will assess outcomes in the overall population and in patients with ejection fraction (EF)
Published: 2022

34. Biomarkers in heart failure clinical trials. A review from the Biomarkers Working Group of the Heart Failure Association of the European Society of Cardiology

Author: Bayes-Genis, A, Aimo, A, Jhund, P, Richards, M, De Boer, RA, Arfsten, H, Fabiani, I, Lupon, J, Anker, SD, Gonzalez, A, Castiglione, V, Metra, M, Mueller, C, Nunez, J, Rossignol, P, Barison, A, Butler, J, Teerlink, J, Filippatos, G, Ponikowski, P, Vergaro, G, Zannad, F, Seferovic, P, Rosano, G, Coats, AJS, Emdin, M, and Januzzi, JL
Subjects: Inclusion, Clinical trials, Natriuretic peptides, Omics, Criteria, Biomarkers, Risk prediction
Abstract: The approval of new heart failure (HF) therapies has slowed over the past two decades in part due to the high costs of conducting large randomized clinical trials that are needed to adequately power major clinical endpoint studies. Several biomarkers have been identified reflecting different elements of HF pathophysiology, with possible applications in diagnosis, risk stratification, treatment monitoring, and even in the design of clinical trials. Biomarkers could potentially be used to refine study inclusion criteria to enable enrolment of patients who are more likely to respond to a therapeutic intervention, despite being at sufficient risk to meet pre-determined study endpoint rates. When there is a close relationship between biomarker levels and clinical endpoints, changes in biomarker levels after a given treatment can act as a surrogate endpoint, potentially reducing the duration and cost of a clinical trial. Natriuretic peptides have been widely used in clinical trials with a variable amount of added value, which such variation being probably due to the absence of a close pathophysiological connection to the study drug. Notable exceptions to this include sacubitril/valsartan and vericiguat. Future studies should seek to adopt unbiased approaches for discovery of true companion diagnostics; with -omics-based tools, biomarkers might be more precisely selected for use in clinical trials to identify responses that closely reflect the biological effects of the drug under investigation. Finally, biomarkers associated with cardiac damage and remodelling, such as cardiac troponin, could be employed as safety endpoints provided that standardization between different assays is achieved.
Published: 2022

35. Effect of empagliflozin in patients with heart failure across the spectrum of left ventricular ejection fraction

Author: Butler, J. Packer, M. Filippatos, G. Ferreira, J.P. Zeller, C. Schnee, J. Brueckmann, M. Pocock, S.J. Zannad, F. Anker, S.D.
Subjects: animal structures
Abstract: AIMS: No therapy has shown to reduce the risk of hospitalization for heart failure across the entire range of ejection fractions seen in clinical practice. We assessed the influence of ejection fraction on the effect of the sodium-glucose cotransporter 2 inhibitor empagliflozin on heart failure outcomes. METHODS AND RESULTS: A pooled analysis was performed on both the EMPEROR-Reduced and EMPEROR-Preserved trials (9718 patients; 4860 empagliflozin and 4858 placebo), and patients were grouped based on ejection fraction
Published: 2022

36. Telomere length is independently associated with all-cause mortality in chronic heart failure

Author: Romaine, S.P.R. Denniff, M. Codd, V. Nath, M. Koekemoer, A. Anker, S.D. Cleland, J.G. Filippatos, G. Levin, D. Metra, M. Mordi, I.R. Ouwerkerk, W. Ter Maaten, J.M. Van Veldhuisen, D.J. Zannad, F. Ng, L.L. Van Der Harst, P. Lang, C.C. Voors, A.A. Nelson, C.P. Samani, N.J.
Abstract: Objective Patients with heart failure have shorter mean leucocyte telomere length (LTL), a marker of biological age, compared with healthy subjects, but it is unclear whether this is of prognostic significance. We therefore sought to determine whether LTL is associated with outcomes in patients with heart failure. Methods We measured LTL in patients with heart failure from the BIOSTAT-CHF Index (n=2260) and BIOSTAT-CHF Tayside (n=1413) cohorts. Cox proportional hazards analyses were performed individually in each cohort and the estimates combined using meta-analysis. Our co-primary endpoints were all-cause mortality and heart failure hospitalisation. Results In age-adjusted and sex-adjusted analyses, shorter LTL was associated with higher all-cause mortality in both cohorts individually and when combined (meta-analysis HR (per SD decrease in LTL)=1.16 (95% CI 1.08 to 1.24); p=2.66×10 -5), an effect equivalent to that of being four years older. The association remained significant after adjustment for the BIOSTAT-CHF clinical risk score to account for known prognostic factors (HR=1.12 (95% CI 1.05 to 1.20); p=1.04×10 -3). Shorter LTL was associated with both cardiovascular (HR=1.09 (95% CI 1.00 to 1.19); p=0.047) and non-cardiovascular deaths (HR=1.18 (95% CI 1.05 to 1.32); p=4.80×10 -3). There was no association between LTL and heart failure hospitalisation (HR=0.99 (95% CI 0.92 to 1.07); p=0.855). Conclusion In patients with heart failure, shorter mean LTL is independently associated with all-cause mortality. © Authors 2021
Published: 2022

37. Mineralocorticoid Receptor Antagonists and Empagliflozin in Patients With Heart Failure and Preserved Ejection Fraction

Author: Ferreira, J.P. Butler, J. Zannad, F. Filippatos, G. Schueler, E. Steubl, D. Zeller, C. Januzzi, J.L. Pocock, S. Packer, M. Anker, S.D.
Subjects: cardiovascular system, cardiovascular diseases, eye diseases, nervous system diseases, circulatory and respiratory physiology
Abstract: Background: Mineralocorticoid receptor antagonists (MRAs) may be beneficial in reducing heart failure (HF) hospitalizations in patients with HF with preserved ejection fraction. The effect of sodium-glucose cotransporter 2 inhibitors in patients with HF with preserved ejection fraction according to MRA background therapy has not been reported. Objectives: The aim of this study was to examine the effect of empagliflozin in MRA users and nonusers in the EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction) trial. Methods: Survival analyses were conducted comparing the effects of empagliflozin vs placebo in MRA users and nonusers at baseline with treatment-by-MRA use interaction terms. Results: A total of 5,988 patients were included, of whom 2,244 (37.5%) were using MRAs at baseline. MRA users had higher event rates than MRA nonusers (placebo group primary outcome 9.4 vs 8.2 events per 100 person-years). The benefit of empagliflozin to reduce the primary outcome was not significantly different between MRA nonusers and MRA users (HR: 0.73 [95% CI: 0.62-0.87] and HR: 0.87 [95% CI: 0.71-1.06]; interaction P = 0.22). The effect of empagliflozin to reduce first and recurrent HF hospitalizations was more pronounced in MRA nonusers than in MRA users (HR: 0.60 [95% CI: 0.47-0.77] and HR: 0.90 [95% CI: 0.68-1.19]; interaction P = 0.038). MRA users experienced almost twice as many hyperkalemia events as MRA nonusers, and empagliflozin reduced the risk for hyperkalemia or initiation of potassium binders regardless of MRA use (MRA nonusers: HR: 0.90 [95% CI: 0.69-1.19]; MRA users: HR: 0.74 [95% CI: 0.56-0.96]; interaction P = 0.29). Conclusions: The benefit of empagliflozin to reduce the primary outcome was not significantly different between MRA nonusers and MRA users. The effect of empagliflozin to reduce first and recurrent HF hospitalizations was more pronounced in MRA nonusers. Empagliflozin reduced hyperkalemia, with no significant treatment-by-MRA subgroup interaction. (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction [EMPEROR-Preserved]; NCT03057951) © 2022 The Authors
Published: 2022

38. Empagliflozin, Health Status, and Quality of Life in Patients With Heart Failure and Preserved Ejection Fraction: The EMPEROR-Preserved Trial

Author: Butler, J. Filippatos, G. Jamal Siddiqi, T. Brueckmann, M. Böhm, M. Chopra, V.K. Pedro Ferreira, J. Januzzi, J.L. Kaul, S. Piña, I.L. Ponikowski, P. Shah, S.J. Senni, M. Vedin, O. Verma, S. Peil, B. Pocock, S.J. Zannad, F. Packer, M. Anker, S.D.
Abstract: BACKGROUND: Patients with heart failure with preserved ejection fraction have significant impairment in health-related quality of life. In the EMPEROR-Preserved trial (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction), we evaluated the efficacy of empagliflozin on health-related quality of life in patients with heart failure with preserved ejection fraction and whether the clinical benefit observed with empagliflozin varies according to baseline health status. METHODS: Health-related quality of life was measured with the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline and 12, 32, and 52 weeks. Patients were divided by baseline KCCQ Clinical Summary Score (CSS) tertiles, and the effect of empagliflozin on outcomes was examined. The effect of empagliflozin on KCCQ-CSS, Total Symptom Score, and Overall Summary Score was evaluated. Responder analyses were performed to compare the odds of improvement and deterioration in KCCQ related to treatment with empagliflozin. RESULTS: The effect of empagliflozin on reducing the risk of time to cardiovascular death or heart failure hospitalization was consistent across baseline KCCQ-CSS tertiles (hazard ratio, 0.83 [95% CI, 0.69-1.00], 0.70 [95% CI, 0.55-0.88], and 0.82 [95% CI, 0.62-1.08] for scores
Published: 2022

39. Clinical impact of changes in mitral regurgitation severity after medical therapy optimization in heart failure

Author: Pagnesi, M. Adamo, M. Sama, I.E. Anker, S.D. Cleland, J.G. Dickstein, K. Filippatos, G.S. Inciardi, R.M. Lang, C.C. Lombardi, C.M. Ng, L.L. Ponikowski, P. Samani, N.J. Zannad, F. van Veldhuisen, D.J. Voors, A.A. Metra, M.
Abstract: Background: Few data are available regarding changes in mitral regurgitation (MR) severity with guideline-recommended medical therapy (GRMT) in heart failure (HF). Our aim was to evaluate the evolution and impact of MR after GRMT in the Biology study to Tailored treatment in chronic heart failure (BIOSTAT-CHF). Methods: A retrospective post-hoc analysis was performed on HF patients from BIOSTAT-CHF with available data on MR status at baseline and at 9-month follow-up after GRMT optimization. The primary endpoint was a composite of all-cause death or HF hospitalization. Results: Among 1022 patients with data at both time-points, 462 (45.2%) had moderate-severe MR at baseline and 360 (35.2%) had it at 9-month follow-up. Regression of moderate-severe MR from baseline to 9 months occurred in 192/462 patients (41.6%) and worsening from baseline to moderate-severe MR at 9 months occurred in 90/560 patients (16.1%). The presence of moderate-severe MR at 9 months, independent from baseline severity, was associated with an increased risk of the primary endpoint (unadjusted hazard ratio [HR], 2.03; 95% confidence interval [CI], 1.57–2.63; p < 0.001), also after adjusting for the BIOSTAT-CHF risk-prediction model (adjusted HR, 1.85; 95% CI 1.43–2.39; p < 0.001). Younger age, LVEF ≥ 50% and treatment with higher ACEi/ARB doses were associated with a lower likelihood of persistence of moderate-severe MR at 9 months, whereas older age was the only predictor of worsening MR. Conclusions: Among patients with HF undergoing GRMT optimization, ACEi/ARB up-titration and HFpEF were associated with MR improvement, and the presence of moderate-severe MR after GRMT was associated with worse outcome. Graphical abstract: [Figure not available: see fulltext.] © 2022, The Author(s).
Published: 2022

40. Supplement to: Adaptive servo-ventilation for central sleep apnea in systolic heart failure.

Author: Cowie, M R, Woehrle, H, Wegscheider, K, Angermann, C, dʼOrtho, M-P, Erdmann, E, Levy, P, Simonds, A K, Somers, V K, Zannad, F, and Teschler, H
Published: 2015

41. Integrating High-Sensitivity Troponin T and Sacubitril/Valsartan Treatment in HFpEF: The PARAGON-HF Trial

Author: Gori M, Senni M, Claggett B, Liu J, Maggioni AP, Zile M, Prescott MF, Van Veldhuisen DJ, Zannad F, Pieske B, Lam CSP, Rouleau J, Jhund P, Packer M, Pfeffer MA, Lefkowitz M, Shi V, McMurray JJV, Solomon SD, Gori, M, Senni, M, Claggett, B, Liu, J, Maggioni, A, Zile, M, Prescott, M, Van Veldhuisen, D, Zannad, F, Pieske, B, Lam, C, Rouleau, J, Jhund, P, Packer, M, Pfeffer, M, Lefkowitz, M, Shi, V, Mcmurray, J, and Solomon, S
Subjects: sacubitril/valsartan, high-sensitivity troponin, HFpEF
Abstract: Objectives: This study examined the relationship among high-sensitivity troponin-T (hs-TnT), outcomes, and treatment with sacubitril/valsartan in patients with heart failure (HF) and preserved ejection fraction (HFpEF). Background: hs-TnT is a marker of myocardial injury in HF. Methods: The PARAGON-HF trial randomized 4,796 patients with HFpEF to sacubitril/valsartan or valsartan. We compared the risk of the composite outcome of cardiovascular death (CVD) and total HF hospitalization (HHF) according to hs-TnT. We also assessed the effect of allocated treatment on hs-TnT. Results: hs-TnT was available in 1,141 patients (24%) at run-in (median value: 17 ng/L) and 1,260 (26%) at randomization, with 58.3% having hs-TnT >14 ng/L (upper limit of normal). During a median follow-up of 34 months, there were 393 outcome events (82 CVD, 311 HHF). Adjusting for demographics, comorbidities, left ventricular ejection fraction (LVEF), and N-terminal pro B-type natriuretic peptide (NT-proBNP), log-hs-TnT at randomization was an independent predictor of the composite outcome (HR: 1.38; 95% CI: 1.19-1.59; P < 0.001). Compared with valsartan, sacubitril/valsartan significantly reduced hs-TnT by 9% at week 16 (P < 0.001). Patients whose hs-TnT decreased from randomization to 16 weeks to at or below the median value of 17 ng/L subsequently had a lower risk of CVD/HHF compared with those with persistently elevated hs-TnT (P = 0.046). Patients with higher baseline hs-TnT (>17 ng/L) appeared to have a greater benefit from sacubitril/valsartan treatment when accounting for other potential effect modifiers (P interaction = 0.07). Conclusions: Higher baseline hs-TnT was associated with increased risk of CVD/HHF, whereas hs-TnT decrease at 16 weeks led to lower subsequent risk of CVD/HHF compared with those who had persistently elevated values. Sacubitril/valsartan significantly reduced hs-TnT compared with valsartan. hs-TnT may be helpful in identifying patients with HFpEF who are more likely to benefit from sacubitril/valsartan.
Published: 2021

42. 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: Verma, Subodh, primary, Dhingra, Nitish K, additional, Butler, Javed, additional, Anker, Stefan D, additional, Ferreira, Joao Pedro, additional, Filippatos, Gerasimos, additional, Januzzi, James L, additional, Lam, Carolyn S P, additional, Sattar, Naveed, additional, Peil, Barbara, additional, Nordaby, Matias, additional, Brueckmann, Martina, additional, Pocock, Stuart J, additional, Zannad, Faiez, additional, Packer, Milton, additional, Packer, M, additional, Anker, S, additional, Butler, J, additional, Filippatos, G, additional, Pocock, S, additional, Zannad, F, additional, Ferreira, JP, additional, Brueckmann, M, additional, George, J, additional, Jamal, W, additional, Welty, FK, additional, Palmer, M, additional, Clayton, T, additional, Parhofer, KG, additional, Pedersen, TR, additional, Greenberg, B, additional, Konstam, MA, additional, Lees, KR, additional, Carson, P, additional, Doehner, W, additional, Miller, A, additional, Haas, M, additional, Pehrson, S, additional, Komajda, M, additional, Anand, I, additional, Teerlink, J, additional, Rabinstein, A, additional, Steiner, T, additional, Kamel, H, additional, Tsivgoulis, G, additional, Lewis, J, additional, Freston, J, additional, Kaplowitz, N, additional, Mann, J, additional, Petrie, J, additional, Perrone, S, additional, Nicholls, S, additional, Janssens, S, additional, Bocchi, E, additional, Giannetti, N, additional, Verma, S, additional, Zhang, J, additional, Spinar, J, additional, Seronde, M-F, additional, Boehm, M, additional, Merkely, B, additional, Chopra, V, additional, Senni, M, additional, Taddi, S, additional, Tsutsui, H, additional, Choi, D-J, additional, Chuquiure, E, additional, La Rocca, HPB, additional, Ponikowski, P, additional, Juanatey, JRG, additional, Squire, I, additional, Januzzi, J, additional, Pina, I, additional, Bernstein, R, additional, Cheung, A, additional, Green, J, additional, Kaul, S, additional, Lam, C, additional, Lip, G, additional, Marx, N, additional, McCullough, P, additional, Mehta, C, additional, Rosenstock, J, additional, Sattar, N, additional, Scirica, B, additional, Shah, S, additional, Wanner, C, additional, Aizenberg, D, additional, Cartasegna, L, additional, Colombo Berra, F, additional, Colombo, H, additional, Fernandez Moutin, M, additional, Glenny, J, additional, Alvarez Lorio, C, additional, Anauch, D, additional, Campos, R, additional, Facta, A, additional, Fernandez, A, additional, Ahuad Guerrero, R, additional, Lobo Márquez, L, additional, Leon de la Fuente, RA, additional, Mansilla, M, additional, Hominal, M, additional, Hasbani, E, additional, Najenson, M, additional, Moises Azize, G, additional, Luquez, H, additional, Guzman, L, additional, Sessa, H, additional, Amuchástegui, M, additional, Salomone, O, additional, Perna, E, additional, Piskorz, D, additional, Sicer, M, additional, Perez de Arenaza, D, additional, Zaidman, C, additional, Nani, S, additional, Poy, C, additional, Resk, J, additional, Villarreal, R, additional, Majul, C, additional, Smith Casabella, T, additional, Sassone, S, additional, Liberman, A, additional, Carnero, G, additional, Caccavo, A, additional, Berli, M, additional, Budassi, N, additional, Bono, J, additional, Alvarisqueta, A, additional, Amerena, J, additional, Kostner, K, additional, Hamilton, A, additional, Begg, A, additional, Beltrame, J, additional, Colquhoun, D, additional, Gordon, G, additional, Sverdlov, A, additional, Vaddadi, G, additional, Wong, J, additional, Coller, J, additional, Prior, D, additional, Friart, A, additional, Leone, A, additional, Vervoort, G, additional, Timmermans, P, additional, Troisfontaines, P, additional, Franssen, C, additional, Sarens, T, additional, Vandekerckhove, H, additional, Van De Borne, P, additional, Chenot, F, additional, De Sutter, J, additional, De Vuyst, E, additional, Debonnaire, P, additional, Dupont, M, additional, Pereira Dutra, O, additional, Canani, LH, additional, Vieira Moreira, MdC, additional, de Souza, W, additional, Backes, LM, additional, Maia, L, additional, De Souza Paolino, B, additional, Manenti, ER, additional, Saporito, W, additional, Villaça Guimarães Filho, F, additional, Franco Hirakawa, T, additional, Saliba, LA, additional, Neuenschwander, FC, additional, de Freitas Zerbini, CA, additional, Gonçalves, G, additional, Gonçalves Mello, Y, additional, Ascenção de Souza, J, additional, Beck da Silva Neto, L, additional, Bocchi, EA, additional, Da Silveira, J, additional, de Moura Xavier Moraes Junior, JB, additional, de Souza Neto, JD, additional, Hernandes, M, additional, Finimundi, HC, additional, Sampaio, CR, additional, Vasconcellos, E, additional, Neves Mancuso, FJ, additional, Noya Rabelo, MM, additional, Rodrigues Bacci, M, additional, Santos, F, additional, Vidotti, M, additional, Simões, MV, additional, Gomes, FL, additional, Vieira Nascimento, C, additional, Precoma, D, additional, Helfenstein Fonseca, FA, additional, Ribas Fortes, JA, additional, Leães, PE, additional, Campos de Albuquerque, D, additional, Kerr Saraiva, JF, additional, Rassi, S, additional, Alves da Costa, FA, additional, Reis, G, additional, Zieroth, S, additional, Dion, D, additional, Savard, D, additional, Bourgeois, R, additional, Constance, C, additional, Anderson, K, additional, Leblanc, M-H, additional, Yung, D, additional, Swiggum, E, additional, Pliamm, L, additional, Pesant, Y, additional, Tyrrell, B, additional, Huynh, T, additional, Spiegelman, J, additional, Lavoie, J-P, additional, Hartleib, M, additional, Bhargava, R, additional, Straatman, L, additional, Virani, S, additional, Costa-Vitali, A, additional, Hill, L, additional, Heffernan, M, additional, Khaykin, Y, additional, Ricci, J, additional, Senaratne, M, additional, Zhai, A, additional, Lubelsky, B, additional, Toma, M, additional, Yao, L, additional, McKelvie, R, additional, Noronha, L, additional, Babapulle, M, additional, Pandey, A, additional, Curnew, G, additional, Lavoie, A, additional, Berlingieri, J, additional, Kouz, S, additional, Lonn, E, additional, Chehayeb, R, additional, Zheng, Y, additional, Sun, Y, additional, Cui, H, additional, Fan, Z, additional, Han, X, additional, Jiang, X, additional, Tang, Q, additional, Zhou, J, additional, Zheng, Z, additional, Zhang, X, additional, Zhang, N, additional, Zhang, Y, additional, Shen, A, additional, Yu, J, additional, Ye, J, additional, Yao, Y, additional, Yan, J, additional, Xu, X, additional, Wang, Z, additional, Ma, J, additional, Li, Y, additional, Li, S, additional, Lu, S, additional, Kong, X, additional, Song, Y, additional, Yang, G, additional, Yao, Z, additional, Pan, Y, additional, Guo, X, additional, Sun, Z, additional, Dong, Y, additional, Zhu, J, additional, Peng, D, additional, Yuan, Z, additional, Lin, J, additional, Yin, Y, additional, Jerabek, O, additional, Burianova, H, additional, Fiala, T, additional, Hubac, J, additional, Ludka, O, additional, Monhart, Z, additional, Vodnansky, P, additional, Zeman, K, additional, Foldyna, D, additional, Krupicka, J, additional, Podpera, I, additional, Busak, L, additional, Radvan, M, additional, Vomacka, Z, additional, Prosecky, R, additional, Cifkova, R, additional, Durdil, V, additional, Vesely, J, additional, Vaclavik, J, additional, Cervinka, P, additional, Linhart, A, additional, Brabec, T, additional, Miklik, R, additional, Bourhaial, H, additional, Olbrich, H-G, additional, Genth-Zotz, S, additional, Kemala, E, additional, Lemke, B, additional, Böhm, M, additional, Schellong, S, additional, Rieker, W, additional, Heitzer, T, additional, Ince, H, additional, Faghih, M, additional, Birkenfeld, A, additional, Begemann, A, additional, Ghanem, A, additional, Ujeyl, A, additional, von Haehling, S, additional, Dorsel, T, additional, Bauersachs, J, additional, Prull, M, additional, Weidemann, F, additional, Darius, H, additional, Nickenig, G, additional, Wilke, A, additional, Sauter, J, additional, Rauch-Kroehnert, U, additional, Frey, N, additional, Schulze, CP, additional, König, W, additional, Maier, L, additional, Menzel, F, additional, Proskynitopoulos, N, additional, Ebert, H-H, additional, Sarnighausen, H-E, additional, Düngen, H-D, additional, Licka, M, additional, Stellbrink, C, additional, Winkelmann, B, additional, Menck, N, additional, López-Sendón, JL, additional, de la Fuente Galán, L, additional, Delgado Jiménez, JF, additional, Manito Lorite, N, additional, Pérez de Juan Romero, M, additional, Galve Basilio, E, additional, Cereto Castro, F, additional, González Juanatey, JR, additional, Gómez, JJ, additional, Sanmartín Fernández, M, additional, Garcia-Moll Marimon, X, additional, Pascual Figal, D, additional, Bover Freire, R, additional, Bonnefoy Cudraz, E, additional, Jobbe Duval, A, additional, Tomasevic, D, additional, Habib, G, additional, Isnard, R, additional, Picard, F, additional, Khanoyan, P, additional, Dubois-Rande, J-L, additional, Galinier, M, additional, Roubille, F, additional, Alexandre, J, additional, Babuty, D, additional, Delarche, N, additional, Berneau, J-B, additional, Girerd, N, additional, Saxena, M, additional, Rosano, G, additional, Yousef, Z, additional, Clifford, C, additional, Arden, C, additional, Bakhai, A, additional, Boos, C, additional, Jenkins, G, additional, Travill, C, additional, Price, D, additional, Koenyves, L, additional, Lakatos, F, additional, Matoltsy, A, additional, Noori, E, additional, Zilahi, Z, additional, Andrassy, P, additional, Kancz, S, additional, Simon, G, additional, Sydo, T, additional, Vorobcsuk, A, additional, Kiss, RG, additional, Toth, K, additional, Szakal, I, additional, Nagy, L, additional, Barany, T, additional, Nagy, A, additional, Szolnoki, E, additional, Chopra, VK, additional, Mandal, S, additional, Rastogi, V, additional, Shah, B, additional, Mullasari, A, additional, Shankar, J, additional, Mehta, V, additional, Oomman, A, additional, Kaul, U, additional, Komarlu, S, additional, Kahali, D, additional, Bhagwat, A, additional, Vijan, V, additional, Ghaisas, NK, additional, Mehta, A, additional, Kashyap, J, additional, Kothari, Y, additional, TaddeI, S, additional, Scherillo, M, additional, Zacà, V, additional, Genovese, S, additional, Salvioni, A, additional, Fucili, A, additional, Fedele, F, additional, Cosmi, F, additional, Volpe, M, additional, Mazzone, C, additional, Esposito, G, additional, Doi, M, additional, Yamamoto, H, additional, Sakagami, S, additional, Oishi, S, additional, Yasaka, Y, additional, Tsuboi, H, additional, Fujino, Y, additional, Matsuoka, S, additional, Watanabe, Y, additional, Himi, T, additional, Ide, T, additional, Ichikawa, M, additional, Kijima, Y, additional, Koga, T, additional, Yuda, S, additional, Fukui, K, additional, Kubota, T, additional, Manita, M, additional, Fujinaga, H, additional, Matsumura, T, additional, Fukumoto, Y, additional, Kato, R, additional, Kawai, Y, additional, Hiasa, G, additional, Kazatani, Y, additional, Mori, M, additional, Ogimoto, A, additional, Inoko, M, additional, Oguri, M, additional, Kinoshita, M, additional, Okuhara, K, additional, Watanabe, N, additional, Ono, Y, additional, Otomo, K, additional, Sato, Y, additional, Matsunaga, T, additional, Takaishi, A, additional, Miyagi, N, additional, Uehara, H, additional, Takaishi, H, additional, Urata, H, additional, Kataoka, T, additional, Matsubara, H, additional, Matsumoto, T, additional, Suzuki, T, additional, Takahashi, N, additional, Imamaki, M, additional, Yoshitama, T, additional, Saito, T, additional, Sekino, H, additional, Furutani, Y, additional, Koda, M, additional, Shinozaki, T, additional, Hirabayashi, K, additional, Tsunoda, R, additional, Yonezawa, K, additional, Hori, H, additional, Yagi, M, additional, Arikawa, M, additional, Hashizume, T, additional, Ishiki, R, additional, Koizumi, T, additional, Nakayama, K, additional, Taguchi, S, additional, Nanasato, M, additional, Yoshida, Y, additional, Tsujiyama, S, additional, Nakamura, T, additional, Oku, K, additional, Shimizu, M, additional, Suwa, M, additional, Momiyama, Y, additional, Sugiyama, H, additional, Kobayashi, K, additional, Inoue, S, additional, Kadokami, T, additional, Maeno, K, additional, Kawamitsu, K, additional, Maruyama, Y, additional, Nakata, A, additional, Shibata, T, additional, Wada, A, additional, Cho, H-J, additional, Na, JO, additional, Yoo, B-S, additional, Choi, J-O, additional, Hong, SK, additional, Shin, J-H, additional, Cho, M-C, additional, Han, SH, additional, Jeong, J-O, additional, Kim, J-J, additional, Kang, SM, additional, Kim, D-S, additional, Kim, MH, additional, Llamas Esperon, G, additional, Illescas Díaz, J, additional, Fajardo Campos, P, additional, Almeida Alvarado, J, additional, Bazzoni Ruiz, A, additional, Echeverri Rico, J, additional, Lopez Alcocer, I, additional, Valle Molina, L, additional, Hernandez Herrera, C, additional, Calvo Vargas, C, additional, Padilla Padilla, FG, additional, Rodriguez Briones, I, additional, Chuquiure Valenzuela, EJJR, additional, Aguilera Real, ME, additional, Carrillo Calvillo, J, additional, Alpizar Salazar, M, additional, Cervantes Escárcega, JL, additional, Velasco Sanchez, R, additional, Al - Windy, N, additional, van Heerebeek, L, additional, Bellersen, L, additional, Brunner-La Rocca, H-P, additional, Post, J, additional, Linssen, GCM, additional, van de Wetering, M, additional, Peters, R, additional, van Stralen, R, additional, Groutars, R, additional, Smits, P, additional, Yilmaz, A, additional, Kok, WEM, additional, Van der Meer, P, additional, Dijkmans, P, additional, Troquay, R, additional, van Alem, AP, additional, Van de Wal, R, additional, Handoko, L, additional, Westendorp, ICD, additional, van Bergen, PFMM, additional, Rensing, BJWM, additional, Hoogslag, P, additional, Kietselaer, B, additional, Kragten, JA, additional, den Hartog, FR, additional, Alings, A, additional, Danilowicz-Szymanowicz, L, additional, Raczak, G, additional, Piesiewicz, W, additional, Zmuda, W, additional, Kus, W, additional, Podolec, P, additional, Musial, W, additional, Drelich, G, additional, Kania, G, additional, Miekus, P, additional, Mazur, S, additional, Janik, A, additional, Spyra, J, additional, Peruga, J, additional, Balsam, P, additional, Krakowiak, B, additional, Szachniewicz, J, additional, Ginel, M, additional, Grzybowski, J, additional, Chrustowski, W, additional, Wojewoda, P, additional, Kalinka, A, additional, Zurakowski, A, additional, Koc, R, additional, Debinski, M, additional, Fil, W, additional, Kujawiak, M, additional, Forys, J, additional, Kasprzak, M, additional, Krol, M, additional, Michalski, P, additional, Mirek-Bryniarska, E, additional, Radwan, K, additional, Skonieczny, G, additional, Stania, K, additional, Skoczylas, G, additional, Madej, A, additional, Jurowiecki, J, additional, Firek, B, additional, Wozakowska-Kaplon, B, additional, Cymerman, K, additional, Neutel, J, additional, Adams, K, additional, Balfour, P, additional, Deswal, A, additional, Djamson, A, additional, Duncan, P, additional, Hong, M, additional, Murray, C, additional, Rinde-Hoffman, D, additional, Woodhouse, S, additional, MacNevin, R, additional, Rama, B, additional, Broome-Webster, C, additional, Kindsvater, S, additional, Abramov, D, additional, Barettella, M, additional, Pinney, S, additional, Herre, J, additional, Cohen, A, additional, Vora, K, additional, Challappa, K, additional, West, S, additional, Baum, S, additional, Cox, J, additional, Jani, S, additional, Karim, A, additional, Akhtar, A, additional, Quintana, O, additional, Paukman, L, additional, Goldberg, R, additional, Bhatti, Z, additional, Budoff, M, additional, Bush, E, additional, Potler, A, additional, Delgado, R, additional, Ellis, B, additional, Dy, J, additional, Fialkow, J, additional, Sangrigoli, R, additional, Ferdinand, K, additional, East, C, additional, Falkowski, S, additional, Donahoe, S, additional, Ebrahimi, R, additional, Kline, G, additional, Harris, B, additional, Khouzam, R, additional, Jaffrani, N, additional, Jarmukli, N, additional, Kazemi, N, additional, Koren, M, additional, Friedman, K, additional, Herzog, W, additional, Silva Enciso, J, additional, Cheung, D, additional, Grover-McKay, M, additional, Hauptman, P, additional, Mikhalkova, D, additional, Hegde, V, additional, Hodsden, J, additional, Khouri, S, additional, McGrew, F, additional, Littlefield, R, additional, Bradley, P, additional, McLaurin, B, additional, Lupovitch, S, additional, Labin, I, additional, Rao, V, additional, Leithe, M, additional, Lesko, M, additional, Lewis, N, additional, Lombardo, D, additional, Mahal, S, additional, Malhotra, V, additional, Dauber, I, additional, Banerjee, A, additional, Needell, J, additional, Miller, G, additional, Paladino, L, additional, Munuswamy, K, additional, Nanna, M, additional, McMillan, E, additional, Mumma, M, additional, Napoli, M, additional, Nelson, W, additional, O'Brien, T, additional, Adlakha, A, additional, Onwuanyi, A, additional, Serota, H, additional, Schmedtje, J, additional, Paraschos, A, additional, Potu, R, additional, Sai-Sudhakar, C, additional, Saltzberg, M, additional, Sauer, A, additional, Shah, P, additional, Skopicki, H, additional, Bui, H, additional, Carr, K, additional, Stevens, G, additional, Tahirkheli, N, additional, Tallaj, J, additional, Yousuf, K, additional, Trichon, B, additional, Welker, J, additional, Tolerico, P, additional, Vest, A, additional, Vivo, R, additional, Wang, X, additional, Abadier, R, additional, Dunlap, S, additional, Weintraub, N, additional, Malik, A, additional, Kotha, P, additional, Zaha, V, additional, Kim, G, additional, Uriel, N, additional, Greene, T, additional, Salacata, A, additional, Arora, R, additional, Gazmuri, R, additional, Kobayashi, J, additional, Iteld, B, additional, Vijayakrishnan, R, additional, Dab, R, additional, Mirza, Z, additional, Marques, V, additional, Nallasivan, M, additional, Bensimhon, D, additional, Peart, B, additional, Saint-Jacques, H, additional, Barringhaus, K, additional, Contreras, J, additional, Gupta, A, additional, Koneru, S, additional, and Nguyen, V, additional
Published: 2022
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43. Preventive and chronic mineralocorticoid receptor antagonism is highly beneficial in obese SHHF rats

Author: Youcef, G, Olivier, A, Nicot, N, Muller, A, Deng, C, Labat, C, Fay, R, Rodriguez-Guéant, R-M, Leroy, C, Jaisser, F, Zannad, F, Lacolley, P, Vallar, L, and Pizard, A
Published: 2016
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44. Plasma fibroblast growth factor 23 is associated with poor outcome and unsuccessful uptitration of guideline-recommended pharmacotherapy in patients with worsening heart failure: 674

Author: Jozine Ter Maaten, J M, Voors, A A, Metra, M, Van Der Harst, P, Dickstein, K, Zannad, F, Cleland, J G, Hillege, H L, Damman, K, and De Borst, M H
Published: 2016

45. Characterisation of a hypercoagulable phenotype with increased thrombin generation in acute heart failure: 134

Author: Popovic, B, Louis, H, Fay, R, Zannad, F, Lacolley, P, and Regnault, V
Published: 2016

46. Evaluation of the effect of sodium–glucose co-transporter 2 inhibition with empagliflozin on morbidity and mortality of patients with chronic heart failure and a reduced ejection fraction: rationale for and design of the EMPEROR-Reduced trial

Author: Packer, M, Butler, J, Filippatos, G, Jamal, W, Salsali, A, Schnee, J, Kimura, K, Zeller, C, George, J, Brueckmann, M, Anker, S, Zannad, F, Perrone, S, Nicholls, S, Janssens, S, Bocchi, E, Giannetti, N, Verma, S, Jian, Z, Spinar, J, Seronde, M, Bohm, M, Merkely, B, Chopra, V, Senni, M, Taddei, S, Tsutsui, H, Choi, D, Chuquiure, E, La Rocca, H, Ponikowski, P, Juanatey, J, Squire, I, Januzzi, J, Pina, I, Pocock, S, 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, M, Bernstein, R, Cheung, A, Green, J, Kaul, S, Ping, C, Lip, G, Marx, N, Mccullough, P, Mehta, C, Rosenstock, J, Sattar, N, Scirica, B, Wanner, C, Welty, F, Parhofer, K, Clayton, T, Pedersen, T, Lees, K, Konstam, M, Greenberg, B, Palmer, M, Packer M., Butler J., Filippatos G. S., Jamal W., Salsali A., Schnee J., Kimura K., Zeller C., George J., Brueckmann M., Anker S. D., Zannad F., Perrone S., Nicholls S., Janssens S., Bocchi E., Giannetti N., Verma S., Jian Z., Spinar J., Seronde M. -F., Bohm M., Merkely B., Chopra V., Senni M., Taddei S., Tsutsui H., Choi D. -J., Chuquiure E., La Rocca H. P. B., Ponikowski P., Juanatey J. R. G., Squire I., Januzzi J., Pina I., Pocock S. J., 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 M., Bernstein R., Cheung A., Green J., Kaul S., Ping C. L. S., Lip G., Marx N., McCullough P., Mehta C., Rosenstock J., Sattar N., Scirica B., Wanner C., Welty F. K., Parhofer K. G., Clayton T., Pedersen T. R., Lees K. R., Konstam M. A., Greenberg B., Palmer M., Packer, M, Butler, J, Filippatos, G, Jamal, W, Salsali, A, Schnee, J, Kimura, K, Zeller, C, George, J, Brueckmann, M, Anker, S, Zannad, F, Perrone, S, Nicholls, S, Janssens, S, Bocchi, E, Giannetti, N, Verma, S, Jian, Z, Spinar, J, Seronde, M, Bohm, M, Merkely, B, Chopra, V, Senni, M, Taddei, S, Tsutsui, H, Choi, D, Chuquiure, E, La Rocca, H, Ponikowski, P, Juanatey, J, Squire, I, Januzzi, J, Pina, I, Pocock, S, 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, M, Bernstein, R, Cheung, A, Green, J, Kaul, S, Ping, C, Lip, G, Marx, N, Mccullough, P, Mehta, C, Rosenstock, J, Sattar, N, Scirica, B, Wanner, C, Welty, F, Parhofer, K, Clayton, T, Pedersen, T, Lees, K, Konstam, M, Greenberg, B, Palmer, M, Packer M., Butler J., Filippatos G. S., Jamal W., Salsali A., Schnee J., Kimura K., Zeller C., George J., Brueckmann M., Anker S. D., Zannad F., Perrone S., Nicholls S., Janssens S., Bocchi E., Giannetti N., Verma S., Jian Z., Spinar J., Seronde M. -F., Bohm M., Merkely B., Chopra V., Senni M., Taddei S., Tsutsui H., Choi D. -J., Chuquiure E., La Rocca H. P. B., Ponikowski P., Juanatey J. R. G., Squire I., Januzzi J., Pina I., Pocock S. J., 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 M., Bernstein R., Cheung A., Green J., Kaul S., Ping C. L. S., Lip G., Marx N., McCullough P., Mehta C., Rosenstock J., Sattar N., Scirica B., Wanner C., Welty F. K., Parhofer K. G., Clayton T., Pedersen T. R., Lees K. R., Konstam M. A., Greenberg B., and Palmer M.
Abstract: Drugs that inhibit the sodium–glucose co-transporter 2 (SGLT2) have been shown to reduce the risk of hospitalizations for heart failure in patients with type 2 diabetes. In populations that largely did not have heart failure at the time of enrolment, empagliflozin, canagliflozin and dapagliflozin decreased the risk of serious new-onset heart failure events by ≈30%. In addition, in the EMPA-REG OUTCOME trial, empagliflozin reduced the risk of both pump failure and sudden deaths, the two most common modes of death among patients with heart failure. In none of the three trials could the benefits of SGLT2 inhibitors on heart failure be explained by the actions of these drugs as diuretics or anti-hyperglycaemic agents. These observations raise the possibility that SGLT2 inhibitors could reduce morbidity and mortality in patients with established heart failure, including those without diabetes. The EMPEROR-Reduced trial is enrolling ≈3600 patients with heart failure and a reduced left ventricular ejection fraction (≤ 40%), half of whom are expected not to have diabetes. Patients are being randomized to placebo or empagliflozin 10 mg daily, which is added to all appropriate treatment with inhibitors of the renin–angiotensin system and neprilysin, beta-blockers and mineralocorticoid receptor antagonists. The primary endpoint is the time-to-first event analysis of the combined risk of cardiovascular death and hospitalization for heart failure, but the trial will also evaluate the effects of empagliflozin on renal function, cardiovascular death, all-cause mortality, and recurrent hospitalization events. By adjusting eligibility based on natriuretic peptide levels to the baseline ejection fraction, the trial will preferentially enrol high-risk patients. A large proportion of the participants is expected to have an ejection fraction < 30%, and the estimated annual event rate is expected to be at least 15%. The EMPEROR-Reduced trial is well-positioned to determine if the addi
Published: 2019

47. Evaluation of the effects of sodium–glucose co-transporter 2 inhibition with empagliflozin on morbidity and mortality in patients with chronic heart failure and a preserved ejection fraction: rationale for and design of the EMPEROR-Preserved Trial

Author: Anker, S, Butler, J, Filippatos, G, Jamal, W, Salsali, A, Schnee, J, Kimura, K, Zeller, C, George, J, Brueckmann, M, Zannad, F, Packer, M, Perrone, S, Nicholls, S, Janssens, S, Bocchi, E, Giannetti, N, Verma, S, Jian, Z, Gomez Mesa, J, Spinar, J, Bohm, M, Merkely, B, Chopra, V, Senni, M, Taddi, S, Tsutsui, H, Chuquiure, E, La Rocca, H, Ponikowski, P, Vinereanu, D, Sim, D, Choi, D, Juanatey, J, Squire, I, Januzzi, J, Pina, I, Pocock, S, 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, M, Bernstein, R, Cheung, A, Green, J, Kaul, S, Ping, C, Lip, G, Marx, N, Mccullough, P, Mehta, C, Rosenstock, J, Sattar, N, Scirica, B, Wanner, C, Welty, F, Parhofer, K, Clayton, T, Pedersen, T, Lees, K, Konstam, M, Greenberg, B, Palmer, M, Anker S. D., Butler J., Filippatos G. S., Jamal W., Salsali A., Schnee J., Kimura K., Zeller C., George J., Brueckmann M., Zannad F., Packer M., Perrone S., Nicholls S., Janssens S., Bocchi E., Giannetti N., Verma S., Jian Z., Gomez Mesa J. E., Spinar J., Bohm M., Merkely B., Chopra V., Senni M., Taddi S., Tsutsui H., Chuquiure E., La Rocca H. P. B., Ponikowski P., Vinereanu D., Sim D., Choi D. -J., Juanatey J. R. G., Squire I., Januzzi J., Pina I., Pocock S. J., 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 M., Bernstein R., Cheung A., Green J., Kaul S., Ping C. L. S., Lip G., Marx N., McCullough P., Mehta C., Rosenstock J., Sattar N., Scirica B., Wanner C., Welty F. K., Parhofer K. G., Clayton T., Pedersen T. R., Lees K. R., Konstam M. A., Greenberg B., Palmer M., Anker, S, Butler, J, Filippatos, G, Jamal, W, Salsali, A, Schnee, J, Kimura, K, Zeller, C, George, J, Brueckmann, M, Zannad, F, Packer, M, Perrone, S, Nicholls, S, Janssens, S, Bocchi, E, Giannetti, N, Verma, S, Jian, Z, Gomez Mesa, J, Spinar, J, Bohm, M, Merkely, B, Chopra, V, Senni, M, Taddi, S, Tsutsui, H, Chuquiure, E, La Rocca, H, Ponikowski, P, Vinereanu, D, Sim, D, Choi, D, Juanatey, J, Squire, I, Januzzi, J, Pina, I, Pocock, S, 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, M, Bernstein, R, Cheung, A, Green, J, Kaul, S, Ping, C, Lip, G, Marx, N, Mccullough, P, Mehta, C, Rosenstock, J, Sattar, N, Scirica, B, Wanner, C, Welty, F, Parhofer, K, Clayton, T, Pedersen, T, Lees, K, Konstam, M, Greenberg, B, Palmer, M, Anker S. D., Butler J., Filippatos G. S., Jamal W., Salsali A., Schnee J., Kimura K., Zeller C., George J., Brueckmann M., Zannad F., Packer M., Perrone S., Nicholls S., Janssens S., Bocchi E., Giannetti N., Verma S., Jian Z., Gomez Mesa J. E., Spinar J., Bohm M., Merkely B., Chopra V., Senni M., Taddi S., Tsutsui H., Chuquiure E., La Rocca H. P. B., Ponikowski P., Vinereanu D., Sim D., Choi D. -J., Juanatey J. R. G., Squire I., Januzzi J., Pina I., Pocock S. J., 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 M., Bernstein R., Cheung A., Green J., Kaul S., Ping C. L. S., Lip G., Marx N., McCullough P., Mehta C., Rosenstock J., Sattar N., Scirica B., Wanner C., Welty F. K., Parhofer K. G., Clayton T., Pedersen T. R., Lees K. R., Konstam M. A., Greenberg B., and Palmer M.
Abstract: Background: The principal biological processes that characterize heart failure with a preserved ejection fraction (HFpEF) are systemic inflammation, epicardial adipose tissue accumulation, coronary microcirculatory rarefaction, myocardial fibrosis and vascular stiffness; the resulting impairment of left ventricular and aortic distensibility (especially when accompanied by impaired glomerular function and sodium retention) causes increases in cardiac filling pressures and exertional dyspnoea despite the relative preservation of left ventricular ejection fraction. Independently of their actions on blood glucose, sodium–glucose co-transporter 2 (SGLT2) inhibitors exert a broad range of biological effects (including actions to inhibit cardiac inflammation and fibrosis, antagonize sodium retention and improve glomerular function) that can ameliorate the pathophysiological derangements in HFpEF. Such SGLT2 inhibitors exert favourable effects in experimental models of HFpEF and have been found in large-scale trials to reduce the risk for serious heart failure events in patients with type 2 diabetes, many of whom were retrospectively identified as having HFpEF. Study design: The EMPEROR-Preserved Trial is enrolling ≈5750 patients with HFpEF (ejection fraction >40%), with and without type 2 diabetes, who are randomized to receive placebo or empagliflozin 10 mg/day, which is added to all appropriate treatments for HFpEF and co-morbidities. Study aims: The primary endpoint is the time-to-first-event analysis of the combined risk for cardiovascular death or hospitalization for heart failure. The trial will also evaluate the effects of empagliflozin on renal function, cardiovascular death,. all-cause mortality and recurrent hospitalization events, and will assess a wide range of biomarkers that reflect important pathophysiological mechanisms that may drive the evolution of HFpEF. The EMPEROR-Preserved Trial is well positioned to determine if empagliflozin can have a meaningfu
Published: 2019

48. Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction

Author: Solomon, S, Mcmurray, J, Anand, I, Ge, J, Lam, C, Maggioni, A, Martinez, F, Packer, M, Pfeffer, M, Pieske, B, Redfield, M, Rouleau, J, van Veldhuisen, D, Zannad, F, Zile, M, Desai, A, Claggett, B, Jhund, P, Boytsov, S, Comin-Colet, J, Cleland, J, Düngen, H, Goncalvesova, E, Katova, T, Kerr Saraiva, J, Lelonek, M, Merkely, B, Senni, M, Shah, S, Zhou, J, Rizkala, A, Gong, J, Shi, V, Lefkowitz, M, PARAGON-HF Investigators and, C, Solomon SD, McMurray JJV, Anand IS, Ge J, Lam CSP, Maggioni AP, Martinez F, Packer M, Pfeffer MA, Pieske B, Redfield MM, Rouleau JL, van Veldhuisen DJ, Zannad F, Zile MR, Desai AS, Claggett B, Jhund PS, Boytsov SA, Comin-Colet J, Cleland J, Düngen HD, Goncalvesova E, Katova T, Kerr Saraiva JF, Lelonek M, Merkely B, Senni M, Shah SJ, Zhou J, Rizkala AR, Gong J, Shi VC, Lefkowitz MP, PARAGON-HF Investigators and Committees, Solomon, S, Mcmurray, J, Anand, I, Ge, J, Lam, C, Maggioni, A, Martinez, F, Packer, M, Pfeffer, M, Pieske, B, Redfield, M, Rouleau, J, van Veldhuisen, D, Zannad, F, Zile, M, Desai, A, Claggett, B, Jhund, P, Boytsov, S, Comin-Colet, J, Cleland, J, Düngen, H, Goncalvesova, E, Katova, T, Kerr Saraiva, J, Lelonek, M, Merkely, B, Senni, M, Shah, S, Zhou, J, Rizkala, A, Gong, J, Shi, V, Lefkowitz, M, PARAGON-HF Investigators and, C, Solomon SD, McMurray JJV, Anand IS, Ge J, Lam CSP, Maggioni AP, Martinez F, Packer M, Pfeffer MA, Pieske B, Redfield MM, Rouleau JL, van Veldhuisen DJ, Zannad F, Zile MR, Desai AS, Claggett B, Jhund PS, Boytsov SA, Comin-Colet J, Cleland J, Düngen HD, Goncalvesova E, Katova T, Kerr Saraiva JF, Lelonek M, Merkely B, Senni M, Shah SJ, Zhou J, Rizkala AR, Gong J, Shi VC, Lefkowitz MP, and PARAGON-HF Investigators and Committees
Abstract: The angiotensin receptor–neprilysin inhibitor sacubitril–valsartan led to a reduced risk of hospitalization for heart failure or death from cardiovascular causes among patients with heart failure and reduced ejection fraction. The effect of angiotensin receptor–neprily-sin inhibition in patients with heart failure with preserved ejection fraction is unclear. METHODS We randomly assigned 4822 patients with New York Heart Association (NYHA) class II to IV heart failure, ejection fraction of 45% or higher, elevated level of natriuretic peptides, and structural heart disease to receive sacubitril–valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or valsartan (target dose, 160 mg twice daily). The primary outcome was a composite of total hospitalizations for heart failure and death from cardiovascular causes. Primary outcome components, secondary outcomes (including NYHA class change, worsening renal function, and change in Kansas City Cardiomyopathy Questionnaire [KCCQ] clinical summary score [scale, 0 to 100, with higher scores indicating fewer symptoms and physical limitations]), and safety were also assessed. RESULTS There were 894 primary events in 526 patients in the sacubitril–valsartan group and 1009 primary events in 557 patients in the valsartan group (rate ratio, 0.87; 95% confidence interval [CI], 0.75 to 1.01; P=0.06). The incidence of death from cardiovascular causes was 8.5% in the sacubitril–valsartan group and 8.9% in the valsartan group (hazard ratio, 0.95; 95% CI, 0.79 to 1.16); there were 690 and 797 total hospitalizations for heart failure, respectively (rate ratio, 0.85; 95% CI, 0.72 to 1.00). NYHA class improved in 15.0% of the patients in the sacubitril–valsartan group and in 12.6% of those in the valsartan group (odds ratio, 1.45; 95% CI, 1.13 to 1.86); renal function worsened in 1.4% and 2.7%, respectively (hazard ratio, 0.50; 95% CI, 0.33 to 0.77). The mean change in the KCCQ clinical summary score at 8 months wa
Published: 2019

49. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19

Author: Zhang Q., Liu Z., Moncada-Velez M., Chen J., Ogishi M., Bigio B., Yang R., Arias A. A., Zhou Q., Han J. E., Ugurbil A. C., Zhang P., Rapaport F., Li J., Spaan A. N., Boisson B., Boisson-Dupuis S., Bustamante J., Puel A., Ciancanelli M. J., Zhang S. -Y., Beziat V., Jouanguy E., Abel L., Cobat A., Casanova J. -L., Bastard P., Korol C., Rosain J., Philippot Q., Chbihi M., Lorenzo L., Bizien L., Neehus A. -L., Kerner G., Seeleuthner Y., Manry J., Le Voyer T., Le Pen J., Schneider W. M., Razooky B. S., Hoffmann H. -H., Michailidis E., Rice C. M., Sabli I. K. D., Hodeib S., Sancho-Shimizu V., Bilguvar K., Ye J., Maniatis T., Bolze A., Zhang Y., Notarangelo L. D., Su H. C., Onodi F., Korniotis S., Karpf L., Soumelis V., Bonnet-Madin L., Amara A., Dorgham K., Gorochov G., Smith N., Duffy D., Moens L., Meyts I., Meade P., Garcia-Sastre A., Krammer F., Corneau A., Masson C., Schmitt Y., Schluter A., Pujol A., Khan T., Marr N., Fellay J., Roussel L., Vinh D. C., Shahrooei M., Alosaimi M. F., Alsohime F., Hasanato R., Mansouri D., Al-Saud H., Almourfi F., Al-Mulla F., Al-Muhsen S. Z., Al Turki S., van de Beek D., Biondi A., Bettini L. R., D'Angio M., Bonfanti P., Imberti L., Sottini A., Paghera S., Quiros-Roldan E., Rossi C., Oler A. J., Tompkins M. F., Alba C., Dalgard C. L., Vandernoot I., Smits G., Goffard J. -C., Migeotte I., Haerynck F., Soler-Palacin P., Martin-Nalda A., Colobran R., Morange P. -E., Keles S., Colkesen F., Ozcelik T., Yasar K. K., Senoglu S., Karabela S. N., Rodriguez-Gallego C., Novelli G., Hraiech S., Tandjaoui-Lambiotte Y., Duval X., Laouenan C., Snow A. L., Milner J. D., Mogensen T. H., Nussenzweig M., Lifton R. P., Foti G., Bellani G., Citerio G., Contro E., Pesci A., Valsecchi M. G., Cazzaniga M., Abad J., Blanco I., Rodrigo C., Aguilera-Albesa S., Akcan O. M., Darazam I. A., Aldave J. C., Ramos M. A., Nadji S. A., Alkan G., Allardet-Servent J., Allende L. M., Alsina L., Alyanakian M. -A., Amador-Borrero B., Mouly S., Sene D., Amoura Z., Mathian A., Antoli A., Blanch G. R., Riera J. S., Moreno X. S., Arslan S., Assant S., Auguet T., Azot A., Bajolle F., Levy R., Oualha M., Baldolli A., Ballester M., Feldman H. B., Barrou B., Beurton A., Bilbao A., Blanchard-Rohner G., Blandinieres A., Rivet N., Blazquez-Gamero D., Bloomfield M., Bolivar-Prados M., Clave P., Borie R., Bosteels C., Lambrecht B. N., van Braeckel E., Bousfiha A. A., Bouvattier C., Vincent A., Boyarchuk O., Bueno M. R. P., Castro M. V., Matos L. R. B., Zatz M., Agra J. J. C., Calimli S., Capra R., Carrabba M., Fabio G., Casasnovas C., Velez-Santamaria V., Caseris M., Falck A., Poncelet G., Castelle M., Castelli F., de Vera M. C., Catherinot E., Chalumeau M., Toubiana J., Charbit B., Li Z., Pellegrini S., Cheng M. P., Clotet B., Codina A., Comarmond C., Dalmau D., Darley D. R., Dauby N., Dauger S., Le Bourgeois F., Levy M., de Pontual L., Dehban A., Delplancq G., Demoule A., Diehl J. -L., Dobbelaere S., Durand S., Mircher C., Rebillat A. -S., Vilaire M. E., Eldars W., Elgamal M., Elnagdy M. H., Emiroglu M., Erdeniz E. H., Aytekin S. E., Euvrard R., Evcen R., Faivre L., Fartoukh M., Faure M., Arquero M. F., Flores C., Francois B., Fumado V., Fusco F., Ursini M. V., Solis B. G., de Diego R. P., van Den Rym A. M., Gaussem P., Gil-Herrera J., Gilardin L., Alarcon M. G., Girona-Alarcon M., Gok F., Yosunkaya A., Gonzalez-Montelongo R., Inigo-Campos A., Lorenzo-Salazar J. M., Munoz-Barrera A., Guerder A., Gul Y., Guner S. N., Gut M., Hadjadj J., Halwani R., Hammarstrom L., Hatipoglu N., Hernandez-Brito E., Heijmans C., Holanda-Pena M. S., Horcajada J. P., Hoste L., Hoste E., Humbert L., Mordacq C., Thumerelle C., Vuotto F., Iglesias A. D., Jamme M., Arranz M. J., Jordan I., Jorens P., Kanat F., Kapakli H., Kara I., Karbuz A., Demirkol Y. K., Klocperk A., Krol Z. J., Kuentz P., Kwan Y. W. M., Lagier J. -C., Lau Y. -L., Leung D., Leo Y. -S., Young B. E., Lopez R. L., Levin M., Linglart A., Loeys B., Louapre C., Lubetzki C., Luyt C. -E., Lye D. C., Marjani M., Pereira J. M., Martin A., Pueyo D. M., Martinez-Picado J., Marzana I., Matthews G. V., Mayaux J., Parizot C., Quentric P., Mege J. -L., Raoult D., Melki I., Meritet J. -F., Metin O., Mezidi M., Taccone F., Millereux M., Mirault T., Mirsaeidi M., Melian A. M., Martinez A. M., Morange P., Morelle G., Naesens L., Nafati C., Neves J. F., Ng L. F. P., Medina Y. N., Cuadros E. N., Gonzalo Ocejo-Vinyals J., Orbak Z., Pan-Hammarstrom Q., Pascreau T., Paz-Artal E., Philippe A., Planas-Serra L., Ploin D., Viel S., Poissy J., Pouletty M., Reisli I., Ricart P., Richard J. -C., Riviere J. G., Rodriguez-Palmero A., Romero C. S., Rothenbuhler A., Rozenberg F., del Prado M. Y. R., Sanchez O., Sanchez-Ramon S., Schmidt M., Schweitzer C. E., Scolari F., Sediva A., Seijo L. M., Seppanen M. R. J., Ilovich A. S., Slabbynck H., Smadja D. M., Sobh A., Sole-Violan J., Soler C., Stepanovskiy Y., Stoclin A., Taupin J. -L., Tavernier S. J., Terrier B., Tomasoni G., Alvarez J. T., Trouillet-Assant S., Troya J., Tucci A., Uzunhan Y., Vabres P., Valencia-Ramos J., van de Velde S., van Praet J., Vatansev H., Vilain C., Voiriot G., Yucel F., Zannad F., Belot A., Bole-Feysot C., Lyonnet S., Nitschke P., Pouliet A., Tores F., Zarhrate M., Andrejak C., Angoulvant F., Bachelet D., Bhavsar K., Bouadma L., Chair A., Couffignal C., Silveira C. D., Debray M. -P., Eloy P., Esposito-Farese M., Ettalhaoui N., Gault N., Ghosn J., Gorenne I., Hoffmann I., Kafif O., Kali S., Khalil A., Laribi S., Le M., Le Hingrat Q., Lescure F. -X., Lucet J. C., Mentre F., Mullaert J., Peiffer-Smadja N., Peytavin G., Roy C., Schneider M., Mohammed N. S., Tagherset L., Tardivon C., Tellier M. -C., Timsit J. -F., Trioux T., Tubiana S., Basmaci R., Behillil S., Beluze M., Benkerrou D., Dorival C., Meziane A., Teoule F., Bompart F., Bouscambert M., Gaymard A., Lina B., Rosa-Calatrava M., Terrier O., Caralp M., Cervantes-Gonzalez M., D'Ortenzio E., Puechal O., Semaille C., Coelho A., Diouf A., Hoctin A., Mambert M., Couffin-Cadiergues S., Deplanque D., Descamps D., Visseaux B., Desvallees M., Khan C., Diallo A., Mercier N., Paul C., Petrov-Sanchez V., Dubos F., Enouf V. V. E., Mouquet H., Esperou H., Jaafoura S., Papadopoulos A., Etienne M., Gigante T., Rossignol B., Guedj J., Le Nagard H., Lingas G., Neant N., Kaguelidou F., Levy Y., Wiedemann A., Levy-Marchal C., Malvy D., Noret M., Pages J., Picone O., Rossignol P., Tual C., Veislinger A., van der Werf S., Vanel N., Yazdanpanah Y., Alavoine L., Costa Y., Ecobichon J. -L., Frezouls W., Ilic-Habensus E., Leclercq A., Lehacaut J., Letrou S., Mandic M., Nouroudine M., Quintin C., Rexach J., Vignali V., Amat K. K. A., Enouf V., Bielicki J., Bruijning P., Burdet C., Caumes E., Charpentier C., Damond F., Coignard B., Delmas C., Roufai L., Dechanet A., Houhou N., Kikoine J., Manchon P., Piquard V., Postolache A., Terzian Z., Lebeaux D., Lucet J. -C., Meghadecha M., Motiejunaite J., Thy M., van Agtmael M., Bomers M., Chouchane O., Geerlings S., Goorhuis B., Grobusch M. P., Harris V., Hermans S. M., Hovius J. W., Nellen J., Peters E., van der Poll T., Prins J. M., Reijnders T., Schinkel M., Sigaloff K., Stijnis C. S., van der Valk M., van Vugt M., Joost Wiersinga W., Algera A. G., van Baarle F., Bos L., Botta M., de Bruin S., Bulle E., Elbers P., Fleuren L., Girbes A., Hagens L., Heunks L., Horn J., van Mourik N., Paulus F., Raasveld J., Schultz M. J., Smit M., Stilma W., Thoral P., Tsonas A., de Vries H., Bax D., Cloherty A., Beudel M., Brouwer M. C., Koning R., Bogaard H. J., de Brabander J., de Bree G., Bugiani M., Geerts B., Hollmann M. W., Preckel B., Veelo D., Geijtenbeek T., Hafkamp F., Hamann J., Hemke R., de Jong M. D., Schuurman A., Teunissen C., Vlaar A. P. J., Wouters D., Zwinderman A. H., Aiuti A., Muhsen S. A., Anderson M. S., Bogunovic D., Itan Y., Cirulli E., Barrett K. S., Washington N., Bondarenko A., Brodin P., Bryceson Y., Bustamante C. D., Butte M., Casari G., Chakravorty S., Christodoulou J., Le Mestre S., Condino-Neto A., Cooper M. A., David A., DeRisi J. L., Desai M., Drolet B. A., Espinosa S., Franco J. L., Gregersen P. K., Hagin D., Heath J., Henrickson S. E., Hsieh E., Imai K., Karamitros T., Kisand K., Ku C. -L., Ling Y., Lucas C. L., Marodi L., Milner J., Mironska K., Mogensen T., Morio T., Novelli A., O'Farrelly C., Okada S., Planas A. M., Prando C., Quintana-Murci L., Renia L., Renieri A., Sankaran V., Snow A., Tangye S., Turvey S., Uddin F., Uddin M. J., Vazquez S. E., von Bernuth H., Zawadzki P., Jing H., Tung W., Meguro K., Shaw E., Shafer S., Zheng L., Zhang Z., Kubo S., Chauvin S. D., Lenardo M., Luthers C. R., Bauman B. M., Lack J., Karlins E., Hupalo D. M., Rosenberger J., Sukumar G., Wilkerson M. D., Zhang X., Rockefeller University [New York], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (UMR_S_944)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris], Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cytométrie Pitié-Salpêtrière (PASS-CYPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), R01AI088364, National Institutes of Health, Howard Hughes Medical Institute, UL1 TR001866, NIH Clinical and Translational Science Award, fast grant, Emergent Ventures, St. Giles Foundation, National Center for Advancing Translational Sciences, Rockefeller University, ANR-10-IAHU-01, Agence Nationale de la Recherche, UM1HG006504 and U24HG008956, National Human Genome Research Institute, ANR-10-LABX-62-IBEID, the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence, EQU201903007798, the French Foundation for Medical Research, Özçelik, Tayfun, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut Pasteur [Paris] (IP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Modeling & analysis for medical imaging and Diagnosis (MYRIAD), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Virologie (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-17-CE15-0003,DENDRISEPSIS,Analyse systémique des cellules présentatrices d'antigène dans le sepsis humain(2017), ANR-20-COVI-0025,iCovid,Immunopathologie du COVID-19 à l'Assistance Publique Hôpitaux de Paris(2020), Zhang, Qian, Bastard, Paul, Le Pen, Jeremie, Moncada-Velez, Marcela, Ogishi, Masato, Sabli, Ira K. D., Hodeib, Stephanie, Korol, Cecilia, Bilguvar, Kaya, Bolze, Alexandre, Bigio, Benedetta, Yang, Rui, Arias, Andrés Augusto, Zhou, Qinhua, Chbihi, Marwa, Bonnet-Madin, Lucie, Dorgham, Karim, Smith, Nikaïa, Schneider, William M., Razooky, Brandon S., Hoffmann, Hans-Heinrich, Michailidis, Eleftherios, Han, Jin Eun, Lorenzo, Lazaro, Bizien, Lucy, Meade, Philip, Neehus, Anna-Lena, Ugurbil, Aileen Camille, Kerner, Gaspard, Zhang, Peng, Rapaport, Franck, Manry, Jérémy, Masson, Cecile, Schlüter, Agatha, Le Voyer, Tom, Khan, Taushif, Fellay, Jacques, Roussel, Lucie, Alosaimi, Mohammed F., Al-Mulla, Fahd, Almourfi, Feras, Alsohime, Fahad, Al Turki, Saeed, Hasanato, Rana, Beek, Diederik van der, Bettini, Laura Rachele, Bonfanti, Paolo, Oler, Andrew J., Tompkins, Miranda F., Alba, Camille, Smits, Guillaume, Soler-Palacín, Pere, Martin-Nalda, Andrea, Colobran, Roger, Çölkesen, Fatma, Yasar, Kadriye Kart, Senoglu, Sevtap, Karabela, Şemsi Nur, Rodríguez-Gallego, Carlos, Novelli, Giuseppe, Tandjaoui-Lambiotte, Yacine, Laouénan, Cédric, Zhang, Q, Bastard, P, Liu, Z, Le Pen, J, Moncada-Velez, M, Chen, J, Ogishi, M, Sabli, I, Hodeib, S, Korol, C, Rosain, J, Bilguvar, K, Ye, J, Bolze, A, Bigio, B, Yang, R, Arias, A, Zhou, Q, Zhang, Y, Onodi, F, Korniotis, S, Karpf, L, Philippot, Q, Chbihi, M, Bonnet-Madin, L, Dorgham, K, Smith, N, Schneider, W, Razooky, B, Hoffmann, H, Michailidis, E, Moens, L, Han, J, Lorenzo, L, Bizien, L, Meade, P, Neehus, A, Ugurbil, A, Corneau, A, Kerner, G, Zhang, P, Rapaport, F, Seeleuthner, Y, Manry, J, Masson, C, Schmitt, Y, Schlüter, A, Le Voyer, T, Khan, T, Li, J, Fellay, J, Roussel, L, Shahrooei, M, Alosaimi, M, Mansouri, D, Al-Saud, H, Al-Mulla, F, Almourfi, F, Al-Muhsen, S, Alsohime, F, Al Turki, S, Hasanato, R, van de Beek, D, Biondi, A, Bettini, L, D'Angio, M, Bonfanti, P, Imberti, L, Sottini, A, Paghera, S, Quiros-Roldan, E, Rossi, C, Oler, A, Tompkins, M, Alba, C, Vandernoot, I, Goffard, J, Smits, G, Migeotte, I, Haerynck, F, Soler-Palacin, P, Martin-Nalda, A, Colobran, R, Morange, P, Keles, S, Çölkesen, F, Ozcelik, T, Yasar, K, Senoglu, S, Karabela, Ş, Gallego, C, Novelli, G, Hraiech, S, Tandjaoui-Lambiotte, Y, Duval, X, Laouénan, C, Snow, A, Dalgard, C, Milner, J, Vinh, D, Mogensen, T, Marr, N, Spaan, A, Boisson, B, Boisson-Dupuis, S, Bustamante, J, Puel, A, Ciancanelli, M, Meyts, I, Maniatis, T, Soumelis, V, Amara, A, Nussenzweig, M, García-Sastre, A, Krammer, F, Pujol, A, Duffy, D, Lifton, R, Zhang, S, Gorochov, G, Béziat, V, Jouanguy, E, Sancho-Shimizu, V, Rice, C, Abel, L, Notarangelo, L, Cobat, A, Su, H, Casanova, J, Pesci, A, Neurology, AII - Infectious diseases, ANS - Neuroinfection & -inflammation, Infectious diseases, ACS - Pulmonary hypertension & thrombosis, Intensive Care Medicine, ACS - Heart failure & arrhythmias, Anesthesiology, ACS - Diabetes & metabolism, ACS - Microcirculation, UKRI Future Leader's Fellowship, Internal medicine, Pulmonary medicine, Intensive care medicine, Pathology, Medical Microbiology and Infection Prevention, Amsterdam Reproduction & Development (AR&D), Amsterdam Neuroscience - Neuroinfection & -inflammation, Laboratory Medicine, APH - Quality of Care, COVID-STORM Clinicians, COVID Clinicians, Imagine COVID Group, French COVID Cohort Study Group, CoV-Contact Cohort, Amsterdam UMC Covid-19 Biobank, COVID Human Genetic Effort, NIAID-USUHS/TAGC COVID Immunity Group, Foti, G., Bellani, G., Citerio, G., Contro, E., Pesci, A., Valsecchi, M.G., Cazzaniga, M., Abad, J., Aguilera-Albesa, S., Akcan, O.M., Darazam, I.A., Aldave, J.C., Ramos, M.A., Nadji, S.A., Alkan, G., Allardet-Servent, J., Allende, L.M., Alsina, L., Alyanakian, M.A., Amador-Borrero, B., Amoura, Z., Antolí, A., Arslan, S., Assant, S., Auguet, T., Azot, A., Bajolle, F., Baldolli, A., Ballester, M., Feldman, H.B., Barrou, B., Beurton, A., Bilbao, A., Blanchard-Rohner, G., Blanco, I., Blandinières, A., Blazquez-Gamero, D., Bloomfield, M., Bolivar-Prados, M., Borie, R., Bosteels, C., Bousfiha, A.A., Bouvattier, C., Boyarchuk, O., Bueno, MRP, Bustamante, J., Cáceres Agra, J.J., Calimli, S., Capra, R., Carrabba, M., Casasnovas, C., Caseris, M., Castelle, M., Castelli, F., de Vera, M.C., Castro, M.V., Catherinot, E., Chalumeau, M., Charbit, B., Cheng, M.P., Clavé, P., Clotet, B., Codina, A., Colkesen, F., Çölkesen, F., Colobran, R., Comarmond, C., Dalmau, D., Darley, D.R., Dauby, N., Dauger, S., de Pontual, L., Dehban, A., Delplancq, G., Demoule, A., Diehl, J.L., Dobbelaere, S., Durand, S., Eldars, W., Elgamal, M., Elnagdy, M.H., Emiroglu, M., Erdeniz, E.H., Aytekin, S.E., Euvrard, R., Evcen, R., Fabio, G., Faivre, L., Falck, A., Fartoukh, M., Faure, M., Arquero, M.F., Flores, C., Francois, B., Fumadó, V., Fusco, F., Solis, B.G., Gaussem, P., Gil-Herrera, J., Gilardin, L., Alarcon, M.G., Girona-Alarcón, M., Goffard, J.C., Gok, F., González-Montelongo, R., Guerder, A., Gul, Y., Guner, S.N., Gut, M., Hadjadj, J., Haerynck, F., Halwani, R., Hammarström, L., Hatipoglu, N., Hernandez-Brito, E., Heijmans, C., Holanda-Peña, M.S., Horcajada, J.P., Hoste, L., Hoste, E., Hraiech, S., Humbert, L., Iglesias, A.D., Íñigo-Campos, A., Jamme, M., Arranz, M.J., Jordan, I., Jorens, P., Kanat, F., Kapakli, H., Kara, I., Karbuz, A., Yasar, K.K., Keles, S., Demirkol, Y.K., Klocperk, A., Król, Z.J., Kuentz, P., Kwan, YWM, Lagier, J.C., Lambrecht, B.N., Lau, Y.L., Le Bourgeois, F., Leo, Y.S., Lopez, R.L., Leung, D., Levin, M., Levy, M., Lévy, R., Li, Z., Linglart, A., Loeys, B., Lorenzo-Salazar, J.M., Louapre, C., Lubetzki, C., Luyt, C.E., Lye, D.C., Mansouri, D., Marjani, M., Pereira, J.M., Martin, A., Pueyo, D.M., Martinez-Picado, J., Marzana, I., Mathian, A., Matos, LRB, Matthews, G.V., Mayaux, J., Mège, J.L., Melki, I., Meritet, J.F., Metin, O., Meyts, I., Mezidi, M., Migeotte, I., Millereux, M., Mirault, T., Mircher, C., Mirsaeidi, M., Melián, A.M., Martinez, A.M., Morange, P., Mordacq, C., Morelle, G., Mouly, S., Muñoz-Barrera, A., Naesens, L., Nafati, C., Neves, J.F., Ng, LFP, Medina, Y.N., Cuadros, E.N., Ocejo-Vinyals, J.G., Orbak, Z., Oualha, M., Özçelik, T., Pan-Hammarström, Q., Parizot, C., Pascreau, T., Paz-Artal, E., Pellegrini, S., de Diego, R.P., Philippe, A., Philippot, Q., Planas-Serra, L., Ploin, D., Poissy, J., Poncelet, G., Pouletty, M., Quentric, P., Raoult, D., Rebillat, A.S., Reisli, I., Ricart, P., Richard, J.C., Rivet, N., Rivière, J.G., Blanch, G.R., Rodrigo, C., Rodriguez-Gallego, C., Rodríguez-Palmero, A., Romero, C.S., Rothenbuhler, A., Rozenberg, F., Ruiz Del Prado, M.Y., Riera, J.S., Sanchez, O., Sánchez-Ramón, S., Schluter, A., Schmidt, M., Schweitzer, C.E., Scolari, F., Sediva, A., Seijo, L.M., Sene, D., Senoglu, S., Seppänen, MRJ, Ilovich, A.S., Shahrooei, M., Slabbynck, H., Smadja, D.M., Sobh, A., Moreno, X.S., Solé-Violán, J., Soler, C., Soler-Palacín, P., Stepanovskiy, Y., Stoclin, A., Taccone, F., Tandjaoui-Lambiotte, Y., Taupin, J.L., Tavernier, S.J., Terrier, B., Thumerelle, C., Tomasoni, G., Toubiana, J., Alvarez, J.T., Trouillet-Assant, S., Troya, J., Tucci, A., Ursini, M.V., Uzunhan, Y., Vabres, P., Valencia-Ramos, J., Van Braeckel, E., Van de Velde, S., Van Den Rym, A.M., Van Praet, J., Vandernoot, I., Vatansev, H., Vélez-Santamaria, V., Viel, S., Vilain, C., Vilaire, M.E., Vincent, A., Voiriot, G., Vuotto, F., Yosunkaya, A., Young, B.E., Yucel, F., Zannad, F., Zatz, M., Belot, A., Bole-Feysot, C., Lyonnet, S., Masson, C., Nitschke, P., Pouliet, A., Schmitt, Y., Tores, F., Zarhrate, M., Abel, L., Andrejak, C., Angoulvant, F., Bachelet, D., Basmaci, R., Behillil, S., Beluze, M., Benkerrou, D., Bhavsar, K., Bompart, F., Bouadma, L., Bouscambert, M., Caralp, M., Cervantes-Gonzalez, M., Chair, A., Coelho, A., Couffignal, C., Couffin-Cadiergues, S., D'Ortenzio, E., Da Silveira, C., Debray, M.P., Deplanque, D., Descamps, D., Desvallées, M., Diallo, A., Diouf, A., Dorival, C., Dubos, F., Duval, X., Eloy, P., Enouf, V.V., Esperou, H., Esposito-Farese, M., Etienne, M., Ettalhaoui, N., Gault, N., Gaymard, A., Ghosn, J., Gigante, T., Gorenne, I., Guedj, J., Hoctin, A., Hoffmann, I., Jaafoura, S., Kafif, O., Kaguelidou, F., Kali, S., Khalil, A., Khan, C., Laouénan, C., Laribi, S., Le, M., Le Hingrat, Q., Le Mestre, S., Le Nagard, H., Lescure, F.X., Lévy, Y., Levy-Marchal, C., Lina, B., Lingas, G., Lucet, J.C., Malvy, D., Mambert, M., Mentré, F., Mercier, N., Meziane, A., Mouquet, H., Mullaert, J., Neant, N., Noret, M., Pages, J., Papadopoulos, A., Paul, C., Peiffer-Smadja, N., Petrov-Sanchez, V., Peytavin, G., Picone, O., Puéchal, O., Rosa-Calatrava, M., Rossignol, B., Rossignol, P., Roy, C., Schneider, M., Semaille, C., Mohammed, N.S., Tagherset, L., Tardivon, C., Tellier, M.C., Téoulé, F., Terrier, O., Timsit, J.F., Trioux, T., Tual, C., Tubiana, S., van der Werf, S., Vanel, N., Veislinger, A., Visseaux, B., Wiedemann, A., Yazdanpanah, Y., Alavoine, L., Amat, KKA, Bielicki, J., Bruijning, P., Burdet, C., Caumes, E., Charpentier, C., Coignard, B., Costa, Y., Damond, F., Dechanet, A., Delmas, C., Ecobichon, J.L., Enouf, V., Espérou, H., Frezouls, W., Houhou, N., Ilic-Habensus, E., Kikoine, J., Lebeaux, D., Leclercq, A., Lehacaut, J., Letrou, S., Manchon, P., Mandic, M., Meghadecha, M., Motiejunaite, J., Nouroudine, M., Piquard, V., Postolache, A., Quintin, C., Rexach, J., Roufai, L., Terzian, Z., Thy, M., Vignali, V., van Agtmael, M., Algera, A.G., van Baarle, F., Bax, D., Beudel, M., Bogaard, H.J., Bomers, M., Bos, L., Botta, M., de Brabander, J., de Bree, G., Brouwer, M.C., de Bruin, S., Bugiani, M., Bulle, E., Chouchane, O., Cloherty, A., Elbers, P., Fleuren, L., Geerlings, S., Geerts, B., Geijtenbeek, T., Girbes, A., Goorhuis, B., Grobusch, M.P., Hafkamp, F., Hagens, L., Hamann, J., Harris, V., Hemke, R., Hermans, S.M., Heunks, L., Hollmann, M.W., Horn, J., Hovius, J.W., de Jong, M.D., Koning, R., van Mourik, N., Nellen, J., Paulus, F., Peters, E., van der Poll, T., Preckel, B., Prins, J.M., Raasveld, J., Reijnders, T., Schinkel, M., Schultz, M.J., Schuurman, A., Sigaloff, K., Smit, M., Stijnis, C.S., Stilma, W., Teunissen, C., Thoral, P., Tsonas, A., van der Valk, M., Veelo, D., Vlaar, APJ, de Vries, H., van Vugt, M., Wiersinga, W.J., Wouters, D., Zwinderman, AHK, van de Beek, D., Aiuti, A., Al Muhsen, S., Al-Mulla, F., Anderson, M.S., Arias, A.A., Bogunovic, D., Bolze, A., Bondarenko, A., Brodin, P., Bryceson, Y., Bustamante, C.D., Butte, M., Casari, G., Chakravorty, S., Christodoulou, J., Cirulli, E., Condino-Neto, A., Cooper, M.A., Dalgard, C.L., David, A., DeRisi, J.L., Desai, M., Drolet, B.A., Espinosa, S., Fellay, J., Franco, J.L., Gregersen, P.K., Hagin, D., Heath, J., Henrickson, S.E., Hsieh, E., Imai, K., Itan, Y., Karamitros, T., Kisand, K., Ku, C.L., Ling, Y., Lucas, C.L., Maniatis, T., Marodi, L., Milner, J., Mironska, K., Mogensen, T., Morio, T., Notarangelo, L.D., Novelli, A., Novelli, G., O'Farrelly, C., Okada, S., Ozcelik, T., Planas, A.M., Prando, C., Pujol, A., Quintana-Murci, L., Renia, L., Renieri, A., Rodríguez-Gallego, C., Sancho-Shimizu, V., Sankaran, V., Barrett, K.S., Snow, A., Spaan, A.N., Tangye, S., Turvey, S., Uddin, F., Uddin, M.J., Vazquez, S.E., Vinh, D.C., von Bernuth, H., Washington, N., Zawadzki, P., Su, H.C., Casanova, J.L., Jing, H., Tung, W., Luthers, C.R., Bauman, B.M., Shafer, S., Zheng, L., Zhang, Z., Kubo, S., Chauvin, S.D., Meguro, K., Shaw, E., Lenardo, M., Lack, J., Karlins, E., Hupalo, D.M., Rosenberger, J., Sukumar, G., Wilkerson, M.D., Zhang, X., Children's Hospital, HUS Children and Adolescents, Clinicum, Department of Medicine, Zhang, Q., Liu, Z., Moncada-Velez, M., Chen, J., Ogishi, M., Bigio, B., Yang, R., Arias, A. A., Zhou, Q., Han, J. E., Ugurbil, A. C., Zhang, P., Rapaport, F., Li, J., Spaan, A. N., Boisson, B., Boisson-Dupuis, S., Puel, A., Ciancanelli, M. J., Zhang, S. -Y., Beziat, V., Jouanguy, E., Cobat, A., Casanova, J. -L., Bastard, P., Korol, C., Rosain, J., Chbihi, M., Lorenzo, L., Bizien, L., Neehus, A. -L., Kerner, G., Seeleuthner, Y., Manry, J., Le Voyer, T., Le Pen, J., Schneider, W. M., Razooky, B. S., Hoffmann, H. -H., Michailidis, E., Rice, C. M., Sabli, I. K. D., Hodeib, S., Bilguvar, K., Ye, J., Zhang, Y., Notarangelo, L. D., Su, H. C., Onodi, F., Korniotis, S., Karpf, L., Soumelis, V., Bonnet-Madin, L., Amara, A., Dorgham, K., Gorochov, G., Smith, N., Duffy, D., Moens, L., Meade, P., Garcia-Sastre, A., Krammer, F., Corneau, A., Khan, T., Marr, N., Roussel, L., Vinh, D. C., Alosaimi, M. F., Alsohime, F., Hasanato, R., Al-Saud, H., Almourfi, F., Al-Muhsen, S. Z., Al Turki, S., Biondi, A., Bettini, L. R., D'Angio, M., Bonfanti, P., Imberti, L., Sottini, A., Paghera, S., Quiros-Roldan, E., Rossi, C., Oler, A. J., Tompkins, M. F., Alba, C., Dalgard, C. L., Smits, G., Goffard, J. -C., Soler-Palacin, P., Martin-Nalda, A., Morange, P. -E., Yasar, K. K., Karabela, S. N., Laouenan, C., Snow, A. L., Milner, J. D., Mogensen, T. H., Nussenzweig, M., Lifton, R. P., Valsecchi, M. G., Akcan, O. M., Darazam, I. A., Aldave, J. C., Ramos, M. A., Nadji, S. A., Allende, L. M., Alyanakian, M. -A., Antoli, A., Blanch, G. R., Riera, J. S., Moreno, X. S., Levy, R., Feldman, H. B., Blandinieres, A., Clave, P., Lambrecht, B. N., van Braeckel, E., Bousfiha, A. A., Bueno, M. R. P., Castro, M. V., Matos, L. R. B., Agra, J. J. C., Velez-Santamaria, V., de Vera, M. C., Cheng, M. P., Darley, D. R., Diehl, J. -L., Rebillat, A. -S., Vilaire, M. E., Elnagdy, M. H., Erdeniz, E. H., Aytekin, S. E., Arquero, M. F., Fumado, V., Ursini, M. V., Solis, B. G., de Diego, R. P., van Den Rym, A. M., Alarcon, M. G., Girona-Alarcon, M., Gonzalez-Montelongo, R., Inigo-Campos, A., Lorenzo-Salazar, J. M., Munoz-Barrera, A., Guner, S. N., Hammarstrom, L., Holanda-Pena, M. S., Horcajada, J. P., Iglesias, A. D., Arranz, M. J., Demirkol, Y. K., Krol, Z. J., Kwan, Y. W. M., Lagier, J. -C., Lau, Y. -L., Leo, Y. -S., Young, B. E., Lopez, R. L., Luyt, C. -E., Lye, D. C., Pereira, J. M., Pueyo, D. M., Matthews, G. V., Mege, J. -L., Meritet, J. -F., Melian, A. M., Martinez, A. M., Neves, J. F., Ng, L. F. P., Medina, Y. N., Cuadros, E. N., Gonzalo Ocejo-Vinyals, J., Pan-Hammarstrom, Q., Richard, J. -C., Riviere, J. G., Rodriguez-Palmero, A., Romero, C. S., del Prado, M. Y. R., Sanchez-Ramon, S., Schweitzer, C. E., Seijo, L. M., Seppanen, M. R. J., Ilovich, A. S., Smadja, D. M., Sole-Violan, J., Taupin, J. -L., Tavernier, S. J., Alvarez, J. T., van de Velde, S., van Praet, J., Silveira, C. D., Debray, M. -P., Lescure, F. -X., Lucet, J. C., Mentre, F., Mohammed, N. S., Tellier, M. -C., Timsit, J. -F., Teoule, F., Puechal, O., Desvallees, M., Enouf, V. V. E., Levy, Y., Ecobichon, J. -L., Amat, K. K. A., Lucet, J. -C., Grobusch, M. P., Hermans, S. M., Hovius, J. W., Prins, J. M., Stijnis, C. S., Joost Wiersinga, W., Algera, A. G., Schultz, M. J., Brouwer, M. C., Bogaard, H. J., Hollmann, M. W., de Jong, M. D., Vlaar, A. P. J., Zwinderman, A. H., Muhsen, S. A., Anderson, M. S., Barrett, K. S., Bustamante, C. D., Cooper, M. A., Derisi, J. L., Drolet, B. A., Franco, J. L., Gregersen, P. K., Henrickson, S. E., Ku, C. -L., Lucas, C. L., Planas, A. M., Uddin, M. J., Vazquez, S. E., Chauvin, S. D., Luthers, C. R., Bauman, B. M., Hupalo, D. M., Wilkerson, M. D., Zhang, Qian [0000-0002-9040-3289], Bastard, Paul [0000-0002-5926-8437], Le Pen, Jeremie [0000-0001-7025-9526], Moncada-Velez, Marcela [0000-0002-3073-5345], Ogishi, Masato [0000-0003-2421-7389], Sabli, Ira K. D. [0000-0002-0170-2990], Hodeib, Stephanie [0000-0002-5978-6189], Korol, Cecilia [0000-0002-0023-8823], Bilguvar, Kaya [0000-0002-7313-7652], Bolze, Alexandre [0000-0001-7399-2766], Bigio, Benedetta [0000-0001-7291-5638], Yang, Rui [0000-0003-4427-2158], Arias, Andrés Augusto [0000-0002-9478-8403], Zhou, Qinhua [0000-0002-5112-3727], Chbihi, Marwa [0000-0002-2771-851X], Bonnet-Madin, Lucie [0000-0002-9848-3287], Dorgham, Karim [0000-0001-9539-3203], Smith, Nikaïa [0000-0002-0202-612X], Schneider, William M. [0000-0001-9407-6118], Razooky, Brandon S. [0000-0002-5263-1512], Hoffmann, Hans-Heinrich [0000-0003-0554-0244], Michailidis, Eleftherios [0000-0002-9907-4346], Han, Jin Eun [0000-0003-1112-9320], Lorenzo, Lazaro [0000-0001-6648-8684], Bizien, Lucy [0000-0001-9163-9122], Meade, Philip [0000-0002-6754-7209], Neehus, Anna-Lena [0000-0002-8573-6820], Ugurbil, Aileen Camille [0000-0002-9450-3092], Kerner, Gaspard [0000-0003-0146-9428], Zhang, Peng [0000-0002-6129-567X], Rapaport, Franck [0000-0001-6553-2110], Manry, Jérémy [0000-0001-5998-2051], Masson, Cecile [0000-0001-7870-7821], Schlüter, Agatha [0000-0001-6732-1528], Le Voyer, Tom [0000-0002-0630-8626], Khan, Taushif [0000-0002-7917-8965], Fellay, Jacques [0000-0002-8240-939X], Roussel, Lucie [0000-0001-5355-702X], Alosaimi, Mohammed F. [0000-0002-8025-3491], Al-Mulla, Fahd [0000-0001-5409-3829], Almourfi, Feras [0000-0002-5166-4662], Alsohime, Fahad [0000-0002-4979-3895], Al Turki, Saeed [0000-0001-7017-336X], Hasanato, Rana [0000-0002-4697-2222], Beek, Diederik van der [0000-0002-4571-044X], Bettini, Laura Rachele [0000-0002-0280-1704], Bonfanti, Paolo [0000-0001-7289-8823], Oler, Andrew J. [0000-0002-6310-0434], Tompkins, Miranda F. [0000-0003-2941-7515], Alba, Camille [0000-0002-0458-1629], Smits, Guillaume [0000-0003-2845-6758], Soler-Palacín, Pere [0000-0002-0346-5570], Martin-Nalda, Andrea [0000-0002-3590-0186], Colobran, Roger [0000-0002-5964-536X], Çölkesen, Fatma [0000-0001-9545-5179], Yasar, Kadriye Kart [0000-0003-2963-4894], Senoglu, Sevtap [0000-0003-4796-9583], Karabela, Şemsi Nur [0000-0003-2562-3004], Rodríguez-Gallego, Carlos [0000-0002-4344-8644], Novelli, Giuseppe [0000-0002-7781-602X], Tandjaoui-Lambiotte, Yacine [0000-0003-1123-4788], and Laouénan, Cédric [0000-0002-3681-6314]
Subjects: Male, COVID19, Interferon Regulatory Factor-7, [SDV]Life Sciences [q-bio], NF-KAPPA-B, Receptor, Interferon alpha-beta, SUSCEPTIBILITY, susceptibility, Interferon alpha-beta, CoV-Contact Cohort, 0302 clinical medicine, Interferon, Loss of Function Mutation, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 80 and over, Medicine and Health Sciences, Viral, Online, Imagine COVID Group, Child, Adolescent, Adult, Aged, Aged, 80 and over, Alleles, Asymptomatic Infections, Betacoronavirus, COVID-19, Child, Preschool, Coronavirus Infections/genetics, Coronavirus Infections/immunology, Female, Genetic Loci, Genetic Predisposition to Disease, Humans, Infant, Interferon Regulatory Factor-7/deficiency, Interferon Regulatory Factor-7/genetics, Interferon Type I/immunology, Middle Aged, Pandemics, Pneumonia, Viral/genetics, Pneumonia, Viral/immunology, Receptor, Interferon alpha-beta/deficiency, Receptor, Interferon alpha-beta/genetics, SARS-CoV-2, Toll-Like Receptor 3/deficiency, Toll-Like Receptor 3/genetics, Young Adult, Research Articles, 0303 health sciences, Multidisciplinary, COVID Clinicians, deficiency, 3. Good health, Multidisciplinary Sciences, DEFICIENCY, Settore MED/03, 030220 oncology & carcinogenesis, Interferon Type I, Science & Technology - Other Topics, medicine.symptom, Coronavirus Infections, Receptor, medicine.drug, NIAID-USUHS, Research Article, General Science & Technology, HERPES-SIMPLEX ENCEPHALITIS, French COVID Cohort Study Group, Pneumonia, Viral, Immunology, Asymptomatic, Virus, 03 medical and health sciences, Immunity, nf-kappa-b, medicine, Genetics, Preschool, COVID Human Genetic Effort, 030304 developmental biology, Biobank, Science & Technology, business.industry, R-Articles, TAGC COVID Immunity Group, Médecine pathologie humaine, herpes-simplex encephalitis, Pneumonia, Amsterdam UMC Covid-19, medicine.disease, COVID-STORM Clinicians, Toll-Like Receptor 3, 3121 General medicine, internal medicine and other clinical medicine, IRF7, 3111 Biomedicine, business, Interferon type I, Interferon regulatory factors
Abstract: COVID-STORM Clinicians Giuseppe Foti1, Giacomo Bellani 1, Giuseppe Citerio1, Ernesto Contro1, Alberto Pesci2, Maria Grazia Valsecchi3, Marina Cazzaniga4 1Department of Emergency, Anesthesia and Intensive Care, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy. 2Department of Pneumology, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy. 3Center of Bioinformatics and Biostatistics, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy. 4Phase I Research Center, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza IT, COVID Clinicians Jorge Abad1, Sergio Aguilera-Albesa2, Ozge Metin Akcan3, Ilad Alavi Darazam4, Juan C. Aldave5, Miquel Alfonso Ramos6, Seyed Alireza Nadji7, Gulsum Alkan8, Jerome Allardet-Servent9, Luis M. Allende10, Laia Alsina11, Marie-Alexandra Alyanakian12, Blanca Amador-Borrero13, Zahir Amoura14, Arnau Antolí15, Sevket Arslan16, Sophie Assant17, Terese Auguet18, Axelle Azot19, Fanny Bajolle20, Aurélie Baldolli21, Maite Ballester22, Hagit Baris Feldman23, Benoit Barrou24, Alexandra Beurton25, Agurtzane Bilbao26, Geraldine Blanchard-Rohner27, Ignacio Blanco1, Adeline Blandinières28, Daniel Blazquez-Gamero29, Marketa Bloomfield30, Mireia Bolivar-Prados31, Raphael Borie32, Cédric Bosteels33, Ahmed A. Bousfiha34, Claire Bouvattier35, Oksana Boyarchuk36, Maria Rita P. Bueno37, Jacinta Bustamante20, Juan José Cáceres Agra38, Semra Calimli39, Ruggero Capra40, Maria Carrabba41, Carlos Casasnovas42, Marion Caseris43, Martin Castelle44, Francesco Castelli45, Martín Castillo de Vera46, Mateus V. Castro37, Emilie Catherinot47, Martin Chalumeau48, Bruno Charbit49, Matthew P. Cheng50, Père Clavé31, Bonaventura Clotet51, Anna Codina52, Fatih Colkesen53, Fatma Çölkesen54, Roger Colobran55, Cloé Comarmond56, David Dalmau57, David Ross Darley58, Nicolas Dauby59, Stéphane Dauger60, Loic de Pontual61, Amin Dehban62, Geoffroy Delplancq63, Alexandre Demoule64, Jean-Luc Diehl65, Stephanie Dobbelaere66, Sophie Durand67, Waleed Eldars68, Mohamed Elgamal69, Marwa H. Elnagdy70, Melike Emiroglu71, Emine Hafize Erdeniz72, Selma Erol Aytekin73, Romain Euvrard74, Recep Evcen75, Giovanna Fabio41, Laurence Faivre76, Antonin Falck43, Muriel Fartoukh77, Morgane Faure78, Miguel Fernandez Arquero79, Carlos Flores80, Bruno Francois81, Victoria Fumadó82, Francesca Fusco83, Blanca Garcia Solis84, Pascale Gaussem85, Juana Gil-Herrera86, Laurent Gilardin87, Monica Girona Alarcon88, Mònica Girona-Alarcón88, Jean-Christophe Goffard89, Funda Gok90, Rafaela González-Montelongo91, Antoine Guerder92, Yahya Gul93, Sukru Nail Guner93, Marta Gut94, Jérôme Hadjadj95, Filomeen Haerynck96, Rabih Halwani97, Lennart Hammarström98, Nevin Hatipoglu99, Elisa Hernandez-Brito100, Cathérine Heijmans101, María Soledad Holanda-Peña102, Juan Pablo Horcajada103, Levi Hoste104, Eric Hoste105, Sami Hraiech106, Linda Humbert107, Alejandro D. Iglesias108, Antonio Íñigo-Campos91, Matthieu Jamme109, María Jesús Arranz110, Iolanda Jordan111, Philippe Jorens112, Fikret Kanat113, Hasan Kapakli114, Iskender Kara115, Adem Karbuz116, Kadriye Kart Yasar117, Sevgi Keles118, Yasemin Kendir Demirkol119, Adam Klocperk120, Zbigniew J. Król121, Paul Kuentz122, Yat Wah M. Kwan123, Jean-Christophe Lagier124, Bart N. Lambrecht33, Yu-Lung Lau125, Fleur Le Bourgeois60, Yee-Sin Leo126, Rafael Leon Lopez127, Daniel Leung125, Michael Levin128, Michael Levy60, Romain Lévy20, Zhi Li49, Agnes Linglart129, Bart Loeys130, José M. Lorenzo-Salazar91, Céline Louapre131, Catherine Lubetzki131, Charles-Edouard Luyt132, David C. Lye133, Davood Mansouri134, Majid Marjani135, Jesus Marquez Pereira136, Andrea Martin137, David Martínez Pueyo138, Javier Martinez-Picado139, Iciar Marzana140, Alexis Mathian14, Larissa R. B. Matos37, Gail V. Matthews141, Julien Mayaux142, Jean-Louis Mège143, Isabelle Melki144, Jean-François Meritet145, Ozge Metin146, Isabelle Meyts147, Mehdi Mezidi148, Isabelle Migeotte149, Maude Millereux150, Tristan Mirault151, Clotilde Mircher67, Mehdi Mirsaeidi152, Abián Montesdeoca Melián153, Antonio Morales Martinez154, Pierre Morange155, Clémence Mordacq107, Guillaume Morelle156, Stéphane Mouly13, Adrián Muñoz-Barrera91, Leslie Naesens157, Cyril Nafati158, João Farela Neves159, Lisa FP. Ng160, Yeray Novoa Medina161, Esmeralda Nuñez Cuadros162, J. Gonzalo Ocejo-Vinyals163, Zerrin Orbak164, Mehdi Oualha20, Tayfun Özçelik165, Qiang Pan-Hammarström166, Christophe Parizot142, Tiffany Pascreau167, Estela Paz-Artal168, Sandra Pellegrini49, Rebeca Pérez de Diego84, Aurélien Philippe169, Quentin Philippot77, Laura Planas-Serra170, Dominique Ploin171, Julien Poissy172, Géraldine Poncelet43, Marie Pouletty173, Paul Quentric142, Didier Raoult143, Anne-Sophie Rebillat67, Ismail Reisli174, Pilar Ricart175, Jean-Christophe Richard176, Nadia Rivet28, Jacques G. Rivière177, Gemma Rocamora Blanch15, Carlos Rodrigo1, Carlos Rodriguez-Gallego178, Agustí Rodríguez-Palmero179, Carolina Soledad Romero180, Anya Rothenbuhler181, Flore Rozenberg182, Maria Yolanda Ruiz del Prado183, Joan Sabater Riera15, Oliver Sanchez184, Silvia Sánchez-Ramón185, Agatha Schluter170, Matthieu Schmidt186, Cyril E. Schweitzer187, Francesco Scolari188, Anna Sediva189, Luis M. Seijo190, Damien Sene13, Sevtap Senoglu117, Mikko R. J. Seppänen191, Alex Serra Ilovich192, Mohammad Shahrooei62, Hans Slabbynck193, David M. Smadja194, Ali Sobh195, Xavier Solanich Moreno15, Jordi Solé-Violán196, Catherine Soler197, Pere Soler-Palacín137, Yuri Stepanovskiy198, Annabelle Stoclin199, Fabio Taccone149, Yacine Tandjaoui-Lambiotte200, Jean-Luc Taupin201, Simon J. Tavernier202, Benjamin Terrier203, Caroline Thumerelle107, Gabriele Tomasoni204, Julie Toubiana48, Josep Trenado Alvarez205, Sophie Trouillet-Assant206, Jesús Troya207, Alessandra Tucci208, Matilde Valeria Ursini‬83, Yurdagul Uzunhan209, Pierre Vabres210, Juan Valencia-Ramos211, Eva Van Braeckel33, Stijn Van de Velde212, Ana Maria Van Den Rym84, Jens Van Praet213, Isabelle Vandernoot214, Hulya Vatansev215, Valentina Vélez-Santamaria42, Sébastien Viel171, Cédric Vilain216, Marie E. Vilaire67, Audrey Vincent35, Guillaume Voiriot217, Fanny Vuotto107, Alper Yosunkaya90, Barnaby E. Young126, Fatih Yucel218, Faiez Zannad219, Mayana Zatz37, Alexandre Belot220*, Imagine COVID Group Christine Bole-Feysot, Stanislas Lyonnet*, Cécile Masson, Patrick Nitschke, Aurore Pouliet, Yoann Schmitt, Frederic Tores, Mohammed Zarhrate Imagine Institute, Université de Paris, INSERM UMR 1163, Paris, France. *Leader of the Imagine COVID Group., French COVID Cohort Study Group Laurent Abel1, Claire Andrejak2, François Angoulvant3, Delphine Bachelet4, Romain Basmaci5, Sylvie Behillil6, Marine Beluze7, Dehbia Benkerrou8, Krishna Bhavsar4, François Bompart9, Lila Bouadma4, Maude Bouscambert10, Mireille Caralp11, Minerva Cervantes-Gonzalez12, Anissa Chair4, Alexandra Coelho13, Camille Couffignal4, Sandrine Couffin-Cadiergues14, Eric D’Ortenzio12, Charlene Da Silveira4, Marie-Pierre Debray4, Dominique Deplanque15, Diane Descamps16, Mathilde Desvallées17, Alpha Diallo18, Alphonsine Diouf13, Céline Dorival8, François Dubos19, Xavier Duval4, Philippine Eloy4, Vincent VE Enouf20, Hélène Esperou21, Marina Esposito-Farese4, Manuel Etienne22, Nadia Ettalhaoui4, Nathalie Gault4, Alexandre Gaymard10, Jade Ghosn4, Tristan Gigante23, Isabelle Gorenne4, Jérémie Guedj24, Alexandre Hoctin13, Isabelle Hoffmann4, Salma Jaafoura21, Ouifiya Kafif4, Florentia Kaguelidou25, Sabina Kali4, Antoine Khalil4, Coralie Khan17, Cédric Laouénan4, Samira Laribi4, Minh Le4, Quentin Le Hingrat4, Soizic Le Mestre18, Hervé Le Nagard24, François-Xavier Lescure4, Yves Lévy26, Claire Levy-Marchal27, Bruno Lina10, Guillaume Lingas24, Jean Christophe Lucet4, Denis Malvy28, Marina Mambert13, France Mentré4, Noémie Mercier18, Amina Meziane8, Hugo Mouquet20, Jimmy Mullaert4, Nadège Neant24, Marion Noret29, Justine Pages30, Aurélie Papadopoulos21, Christelle Paul18, Nathan Peiffer-Smadja4, Ventzislava Petrov-Sanchez18, Gilles Peytavin4, Olivier Picone31, Oriane Puéchal12, Manuel Rosa-Calatrava10, Bénédicte Rossignol23, Patrick Rossignol32, Carine Roy4, Marion Schneider4, Caroline Semaille12, Nassima Si Mohammed4, Lysa Tagherset4, Coralie Tardivon4, Marie-Capucine Tellier4, François Téoulé8, Olivier Terrier10, Jean-François Timsit4, Théo Trioux4, Christelle Tual33, Sarah Tubiana4, Sylvie van der Werf34, Noémie Vanel35, Aurélie Veislinger33, Benoit Visseaux16, Aurélie Wiedemann26, Yazdan Yazdanpanah36 1Inserm UMR 1163, Paris, France. 2CHU Amiens, France. 3Hôpital Necker, Paris, France. 4Hôpital Bichat, Paris, France. 5Hôpital Louis Mourrier, Colombes, France. 6Institut Pasteur, Paris, France. 7F-CRIN Partners Platform, AP-HP, Université de Paris, Paris, France. 8Inserm UMR 1136, Paris, France. 9Drugs for Neglected Diseases Initiative, Geneva, Switzerland. 10Inserm UMR 1111, Lyon, France. 11Inserm Transfert, Paris, France. 12REACTing, Paris, France. 13Inserm UMR 1018, Paris, France. 14Inserm, Pôle Recherche Clinique, Paris, France. 15CIC 1403 Inserm-CHU Lille, Paris, France. 16Université de Paris, IAME, INSERM UMR 1137, AP-HP, University Hospital Bichat Claude Bernard, Virology, Paris, France. 17Inserm UMR 1219, Bordeaux, France. 18ANRS, Paris, France. 19CHU Lille, Lille, France. 20Pasteur Institute, Paris, France. 21Inserm sponsor, Paris, France. 22CHU Rouen–SMIT, Rouen, France. 23FCRIN INI-CRCT, Nancy, France. 24Inserm UMR 1137, Paris, France. 25Centre d’Investigation Clinique, Inserm CIC1426, Hôpital Robert Debré, Paris, France. 26Inserm UMR 955, Créteil, France; Vaccine Research Instiute (VRI), Paris, France. 27F-CRIN INI-CRCT, Paris, France. 28CHU de Bordeaux–SMIT, Bordeaux, France. 29RENARCI, Annecy, France. 30Hôpital Robert Debré, Paris, France. 31Hôpital Louis Mourier–Gynécologie, Colombes, France. 32University of Lorraine, Plurithematic Clinical Investigation Centre Inserm CIC-P; 1433, Inserm U1116, CHRU Nancy Hopitaux de Brabois, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France. 33Inserm CIC-1414, Rennes, France. 34Institut Pasteur, UMR 3569 CNRS, Université de Paris, Paris, France. 35Hôpital la Timone, Marseille, France. 36Bichat–SMIT, Paris, France., CoV-Contact Cohort Loubna Alavoine1, Karine K. A. Amat2, Sylvie Behillil3, Julia Bielicki4, Patricia Bruijning5, Charles Burdet6, Eric Caumes7, Charlotte Charpentier8, Bruno Coignard9, Yolande Costa1, Sandrine Couffin-Cadiergues10, Florence Damond8, Aline Dechanet11, Christelle Delmas10, Diane Descamps8, Xavier Duval1, Jean-Luc Ecobichon1, Vincent Enouf3, Hélène Espérou10, Wahiba Frezouls1, Nadhira Houhou11, Emila Ilic-Habensus1, Ouifiya Kafif11, John Kikoine11, Quentin Le Hingrat8, David Lebeaux12, Anne Leclercq1, Jonathan Lehacaut1, Sophie Letrou1, Bruno Lina13, Jean-Christophe Lucet14, Denis Malvy15, Pauline Manchon11, Milica Mandic1, Mohamed Meghadecha16, Justina Motiejunaite17, Mariama Nouroudine1, Valentine Piquard11, Andreea Postolache11, Caroline Quintin1, Jade Rexach1, Layidé Roufai10, Zaven Terzian11, Michael Thy18, Sarah Tubiana1, Sylvie van der Werf3, Valérie Vignali1, Benoit Visseaux8, Yazdan Yazdanpanah14 1Centre d’Investigation Clinique, Inserm CIC 1425, Hôpital Bichat Claude Bernard, APHP, Paris, France. 2IMEA Fondation Léon M’Ba, Paris, France. 3Institut Pasteur, UMR 3569 CNRS, Université de Paris, Paris, France. 4University of Basel Children’s Hospital. 5Julius Center for Health Sciences and Primary Care, Utrecht, Netherlands. 6Université de Paris, IAME, Inserm UMR 1137, F-75018, Paris, France, Hôpital Bichat Claude Bernard, APHP, Paris, France. 7Hôpital Pitiè Salpétriere, APHP, Paris. 8Université de Paris, IAME, INSERM UMR 1137, AP-HP, University Hospital Bichat Claude Bernard, Virology, Paris, France. 9Santé Publique France, Saint Maurice, France. 10Pole Recherche Clinique, Inserm, Paris, France. 11Hôpital Bichat Claude Bernard, APHP, Paris, France. 12APHP, Paris, France. 13Virpath Laboratory, International Center of Research in Infectiology, Lyon University, INSERM U1111, CNRS UMR 5308, ENS, UCBL, Lyon, France. 14IAME Inserm UMR 1138, Hôpital Bichat Claude Bernard, APHP, Paris, France. 15Service des Maladies Infectieuses et Tropicales; Groupe Pellegrin-Place Amélie-Raba-Léon, Bordeaux, France. 16Hôpital Hotel Dieu, APHP, Paris, France. 17Service des Explorations Fonctionnelles, Hôpital Bichat–Claude Bernard, APHP, Paris, France. 18Center for Clinical Investigation, Assistance Publique-Hôpitaux de Paris, Bichat-Claude Bernard University Hospital, Paris, France., Amsterdam UMC Covid-19 Biobank Michiel van Agtmael1, Anna Geke Algera2, Frank van Baarle2, Diane Bax3, Martijn Beudel4, Harm Jan Bogaard5, Marije Bomers1, Lieuwe Bos2, Michela Botta2, Justin de Brabander6, Godelieve de Bree6, Matthijs C. Brouwer4, Sanne de Bruin2, Marianna Bugiani7, Esther Bulle2, Osoul Chouchane1, Alex Cloherty3, Paul Elbers2, Lucas Fleuren2, Suzanne Geerlings1, Bart Geerts8, Theo Geijtenbeek9, Armand Girbes2, Bram Goorhuis1, Martin P. Grobusch1, Florianne Hafkamp9, Laura Hagens2, Jorg Hamann10, Vanessa Harris1, Robert Hemke11, Sabine M. Hermans1, Leo Heunks2, Markus W. Hollmann8, Janneke Horn2, Joppe W. Hovius1, Menno D. de Jong12, Rutger Koning4, Niels van Mourik2, Jeaninne Nellen1, Frederique Paulus2, Edgar Peters1, Tom van der Poll1, Benedikt Preckel8, Jan M. Prins1, Jorinde Raasveld2, Tom Reijnders1, Michiel Schinkel1, Marcus J. Schultz2, Alex Schuurman13, Kim Sigaloff1, Marry Smit2, Cornelis S. Stijnis1, Willemke Stilma2, Charlotte Teunissen14, Patrick Thoral2, Anissa Tsonas2, Marc van der Valk1, Denise Veelo8, Alexander P.J. Vlaar15, Heder de Vries2, Michèle van Vugt1, W. Joost Wiersinga1, Dorien Wouters16, A. H. (Koos) Zwinderman17, Diederik van de Beek4* 1Department of Infectious Diseases, Amsterdam UMC, Amsterdam, Netherlands. 2Department of Intensive Care, Amsterdam UMC, Amsterdam, Netherlands. 3Experimental Immunology, Amsterdam UMC, Amsterdam, Netherlands. 4Department of Neurology, Amsterdam UMC, Amsterdam Neuroscience, Amsterdam, Netherlands. 5Department of Pulmonology, Amsterdam UMC, Amsterdam, Netherlands. 6Department of Infectious Diseases, Amsterdam UMC, Amsterdam, Netherlands. 7Department of Pathology, Amsterdam UMC, Amsterdam, Netherlands. 8Department of Anesthesiology, Amsterdam UMC, Amsterdam, Netherlands. 9Department of Experimental Immunology, Amsterdam UMC, Amsterdam, Netherlands. 10Amsterdam UMC Biobank Core Facility, Amsterdam UMC, Amsterdam, Netherlands. 11Department of Radiology, Amsterdam UMC, Amsterdam, Netherlands. 12Department of Medical Microbiology, Amsterdam UMC, Amsterdam, Netherlands. 13Department of Internal Medicine, Amsterdam UMC, Amsterdam, Netherlands. 14Neurochemical Laboratory, Amsterdam UMC, Amsterdam, Netherlands. 15Department of Intensive Care, Amsterdam UMC, Amsterdam, Netherlands. 16Department of Clinical Chemistry, Amsterdam UMC, Amsterdam, Netherlands. 17Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, Amsterdam, Netherlands. 18Department of Neurology, Amsterdam UMC, Amsterdam, Netherlands. *Leader of the AMC Consortium., COVID Human Genetic Effort Laurent Abel1, Alessandro Aiuti2, Saleh Al Muhsen3, Fahd Al-Mulla4, Mark S. Anderson5, Andrés Augusto Arias6, Hagit Baris Feldman7, Dusan Bogunovic8, Alexandre Bolze9, Anastasiia Bondarenko10, Ahmed A. Bousfiha11, Petter Brodin12, Yenan Bryceson12, Carlos D. Bustamante13, Manish Butte14, Giorgio Casari15, Samya Chakravorty16, John Christodoulou17, Elizabeth Cirulli9, Antonio Condino-Neto18, Megan A. Cooper19, Clifton L. Dalgard20, Alessia David21, Joseph L. DeRisi22, Murkesh Desai23, Beth A. Drolet24, Sara Espinosa25, Jacques Fellay26, Carlos Flores27, Jose Luis Franco28, Peter K. Gregersen29, Filomeen Haerynck30, David Hagin31, Rabih Halwani32, Jim Heath33, Sarah E. Henrickson34, Elena Hsieh35, Kohsuke Imai36, Yuval Itan8, Timokratis Karamitros37, Kai Kisand38, Cheng-Lung Ku39, Yu-Lung Lau40, Yun Ling41, Carrie L. Lucas42, Tom Maniatis43, Davoud Mansouri44, Laszlo Marodi45, Isabelle Meyts46, Joshua Milner47, Kristina Mironska48, Trine Mogensen49, Tomohiro Morio50, Lisa FP. Ng51, Luigi D. Notarangelo52, Antonio Novelli53, Giuseppe Novelli54, Cliona O’Farrelly55, Satoshi Okada56, Tayfun Ozcelik57, Rebeca Perez de Diego58, Anna M. Planas59, Carolina Prando60, Aurora Pujol61, Lluis Quintana-Murci62, Laurent Renia63, Alessandra Renieri64, Carlos Rodríguez-Gallego65, Vanessa Sancho-Shimizu66, Vijay Sankaran67, Kelly Schiabor Barrett9, Mohammed Shahrooei68, Andrew Snow69, Pere Soler-Palacín70, András N. Spaan71, Stuart Tangye72, Stuart Turvey73, Furkan Uddin74, Mohammed J. Uddin75, Diederik van de Beek76, Sara E. Vazquez77, Donald C. Vinh78, Horst von Bernuth79, Nicole Washington9, Pawel Zawadzki80, Helen C. Su52, Jean-Laurent Casanova81 1INSERM U1163, University of Paris, Imagine Institute, Paris, France. 2San Raffaele Telethon Institute for Gene Therapy, IRCCS Ospedale San Raffaele, Milan, Italy. 3King Saud University, Riyadh, Saudi Arabia. 4Kuwait University, Kuwait City, Kuwait. 5University of California, San Francisco, San Francisco, CA, USA. 6Universidad de Antioquia, Group of Primary Immunodeficiencies, Antioquia, Colombia. 7The Genetics Institute, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 8Icahn School of Medicine at Mount Sinai, New York, NY, USA. 9Helix, San Mateo, CA, USA. 10Shupyk National Medical Academy for Postgraduate Education, Kiev, Ukraine. 11Clinical Immunology Unit, Pediatric Infectious Disease Departement, Faculty of Medicine and Pharmacy, Averroes University Hospital; LICIA Laboratoire d’Immunologie Clinique, d’Inflammation et d’Allergie, Hassann Ii University, Casablanca, Morocco. 12Karolinska Institute, Stockholm, Sweden. 13Stanford University, Stanford, CA, USA. 14University of California, Los Angeles, CA, USA. 15Medical Genetics, IRCCS Ospedale San Raffaele, Milan, Italy. 16Emory University Department of Pediatrics and Children’s Healthcare of Atlanta, Atlanta, GA, USA. 17Murdoch Children’s Research Institute, Victoria, Australia. 18University of São Paulo, São Paulo, Brazil. 19Washington University School of Medicine, St. Louis, MO, USA. 20The American Genome Center; Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 21Centre for Bioinformatics and System Biology, Department of Life Sciences, Imperial College London, South Kensington Campus, London, UK. 22University of California, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA. 23Bai Jerbai Wadia Hospital for Children, Mumbai, India. 24School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA. 25Instituto Nacional de Pediatria (National Institute of Pediatrics), Mexico City, Mexico. 26Swiss Federal Institute of Technology Lausanne, Lausanne, Switzerland. 27Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Canarian Health System, Santa Cruz de Tenerife, Spain. 28University of Antioquia, Medellín, Colombia. 29Feinstein Institute for Medical Research, Northwell Health USA, Manhasset, NY, USA. 30Department of Paediatric Immunology and Pulmonology, Centre for Primary Immunodeficiency Ghent (CPIG), PID Research Lab, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Edegem, Belgium. 31The Genetics Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. 32Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, UAE. 33Institute for Systems Biology, Seattle, WA, USA. 34Children’s Hospital of Philadelphia, Philadelphia, PA, USA. 35Anschutz Medical Campus, Aurora, CO, USA. 36Riken, Tokyo, Japan. 37Hellenic Pasteur Institute, Athens, Greece. 38University of Tartu, Tartu, Estonia. 39Chang Gung University, Taoyuan County, Taiwan. 40The University of Hong Kong, Hong Kong, China. 41Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. 42Yale School of Medicine, New Haven, CT, USA. 43New York Genome Center, New York, NY, USA. 44Shahid Beheshti University of Medical Sciences, Tehran, Iran. 45Semmelweis University Budapest, Budapest, Hungary. 46KU Leuven, Department of Immunology, Microbiology and Transplantation, Leuven, Belgium. 47Columbia University Medical Center, New York, NY, USA. 48University Clinic for Children’s Diseases, Skopje, North Macedonia. 49Aarhus University, Aarhus, Denmark. 50Tokyo Medical & Dental University Hospital, Tokyo, Japan. 51Singapore Immunology Network, Singapore. 52National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. 53Bambino Gesù Children’s Hospital, Rome, Italy. 54Department of Biomedicine and Prevention, University of Rome “Tor Vergata,” Rome, Italy. 55Trinity College, Dublin, Ireland. 56Hiroshima University, Hiroshima, Japan. 57Bilkent University, Ankara, Turkey. 58Laboratory of Immunogenetics of Human Diseases, Innate Immunity Group, IdiPAZ Institute for Health Research, La Paz Hospital, Madrid, Spain. 59IIBB-CSIC, IDIBAPS, Barcelona, Spain. 60Faculdades Pequeno Príncipe e Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Brazil. 61Neurometabolic Diseases Laboratory, IDIBELL–Hospital Duran I Reynals; Catalan Institution for Research and Advanced Studies (ICREA); CIBERER U759, ISCiii Madrid Spain, Barcelona, Spain. 62Institut Pasteur (CNRS UMR2000) and Collège de France, Paris, France. 63Infectious Diseases Horizontal Technology Center and Singapore Immunology Network, Agency for Science Technology (A*STAR), Singapore. 64Medical Genetics, University of Siena, Siena, Italy; Genetica Medica, Azienda Ospedaliero-Universitaria Senese, Italy; GEN-COVID Multicenter Study. 65Hospital Universitario de Gran Canaria Dr. Negrín, Canarian Health System, Canary Islands, Spain. 66Imperial College London, London, UK. 67Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA. 68Saeed Pathobiology and Genetic Lab, Tehran, Iran. 69Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 70Hospital Universitari Vall d’Hebron, Barcelona, Spain. 71University Medical Center Utrecht, Amsterdam, The Netherlands. 72Garvan Institute of Medical Research, Sydney, Australia. 73The University of British Columbia, Vancouver, Canada. 74Holy Family Red Crescent Medical College; Centre for Precision Therapeutics, NeuroGen Children’s Healthcare; Genetics and Genomic Medicine Centre, NeuroGen Children’s Healthcare, Dhaka, Bangladesh. 75Mohammed Bin Rashid University of Medicine and Health Sciences, College of Medicine, Dubai, UAE; The Centre for Applied Genomics, Department of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada. 76Amsterdam UMC, University of Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam, The Netherlands. 77University of California, San Francisco, CA, USA. 78McGill University Health Centre, Montreal, Canada. 79Charité–Berlin University Hospital Center, Berlin, Germany. 80Molecular Biophysics Division, Faculty of Physics, A. Mickiewicz University, Uniwersytetu Poznanskiego 2, Poznań, Poland. 81Rockefeller University, Howard Hughes Medical Institute, Necker Hospital, New York, NY, USA. *Leaders of the COVID Human Genetic Effort., NIAID-USUHS/TAGC COVID Immunity Group Huie Jing1,2, Wesley Tung1,2, Christopher R. Luthers3, Bradly M. Bauman3, Samantha Shafer2,4, Lixin Zheng2,4, Zinan Zhang2,4, Satoshi Kubo2,4, Samuel D. Chauvin2,4, Kazuyuki Meguro1,2, Elana Shaw1,2, Michael Lenardo2,4, Justin Lack5, Eric Karlins6, Daniel M. Hupalo7, John Rosenberger7, Gauthaman Sukumar7, Matthew D. Wilkerson7, Xijun Zhang7 1Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA. 2NIAID Clinical Genomics Program, National Institutes of Health, Bethesda, MD, USA. 3Department of Pharmacology & Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 4Laboratory of Immune System Biology, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA. 5NIAID Collaborative Bioinformatics Resource, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA. 6Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, NIAID, NIH, Bethesda, MD, USA. 7The American Genome Center, Uniformed Services University of the Health Sciences, Bethesda, MD, USA., Clinical outcome upon infection with SARS-CoV-2 ranges from silent infection to lethal COVID-19. We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern TLR3- and IRF7-dependent type I interferon (IFN) immunity to influenza virus, in 659 patients with life-threatening COVID-19 pneumonia, relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally define LOF variants in 23 patients (3.5%), aged 17 to 77 years, underlying autosomal recessive or dominant deficiencies. We show that human fibroblasts with mutations affecting this pathway are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection., We thank the generous donation from Fisher Center for Alzheimer’s Research Foundation for our research. The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the French National Research Agency (ANR) under the “Investments for the Future” program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project, ANRS-COV05, the Square Foundation, Grandir - Fonds de solidarité pour l’enfance, the SCOR Corporate Foundation for Science, Institut National de la Santé et de la Recherche Médicale (INSERM), the University of Paris. The French COVID Cohort study group was sponsored by Inserm and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). Regione Lombardia, Italy (project “Risposta immune in pazienti con COVID-19 e co-morbidità”), and the Intramural Research Program of the NIAID, NIH. The laboratory of Genomes & Cell Biology of Disease is supported by “Integrative Biology of Emerging Infectious Diseases” (grant no. ANR-10-LABX-62-IBEID), the “Fondation pour la Recherche Medicale” (grant FRM - EQU202003010193), the “Agence Nationale de la Recherche” (ANR FLASH COVID project IDISCOVR cofounded by the “Fondation pour la Recherche Médicale”), University of Paris (“Plan de Soutien Covid-19”: RACPL20FIR01-COVID-SOUL). IM is a senior clinical investigator with the FWO Vlaanderen; IM and LM are supported by FWO G0C8517N – GOB5120N. The VS team was supported by “Agence Nationale de la Recherche” (ANR-17-CE15-0003, ANR-17-CE15-0003-01), and by Université de Paris “PLAN D’URGENCE COVID19”. LK was supported by a fellowship from the French Ministry of Research. VS-S is supported by a UKRI Future Leaders Fellowship (MR/S032304/1). SZA-M is supported by the Elite Journals Program at King Saud University through grant number PEJP-16-107. JM lab is supported by Columbia University COVID biobank and grant: UL1TR001873. Work in the Laboratory of Virology and Infectious Disease was supported by NIH grants P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1, a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. JLP is supported by a European Molecular Biology Organization Long-Term Fellowship (ALTF 380-2018). Work at the Neurometabolic Diseases Laboratory received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 824110 (EasiGenomics grant COVID-19/ PID12342) to A.P., and Roche and Illumina Covid Match Funds to M.G.. C.R.G and colleagues are supported by cInstituto de Salud Carlos III (COV20_01333 and COV20_01334), Spanish Ministry of Science and Innovation, with the funding of European Regional Development Fund-European Social Fund -FEDER-FSE; (RTC-2017-6471-1; AEI/FEDER, UE), and Cabildo Insular de Tenerife (CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). D.C.V. is supported by the Fonds de la recherche en santé du Québec clinician-scientist scholar program. Helen Su is adjunct faculty at the University of Pennsylvania. A-L.N. was supported by the Foundation Bettencourt Schueller. The Amsterdam UMC Covid-19 Biobank was funded by the Netherlands Organization for Health Research and Development (ZonMw, NWO-vici 91819627), The Corona Research Fund (Amsterdam UMC), Dr. J. C. Vaillantfonds, and Amsterdam UMC. Work on COVID-19 at the AG-S lab is partly supported by NIH supplements to grants U19AI135972, U19AI142733 and R35 HL135834, and to contract HHSN272201800048C, by a DoD supplement to grant W81XWH-20-1-0270, by DARPA project HR0011-19-2-0020, by CRIP (Center for Research on Influenza Pathogenesis), a NIAID funded Center of Excellence for Influenza Research and Surveillance (CEIRS, contract HHSN272201400008C), by an NIAID funded Collaborative Influenza Vaccine Innovation Center (SEM-CIVIC, contract 75N93019C00051) and by the generous support of the JPB Foundation, the Open Philanthropy Project (research grant 2020-215611(5384)) and anonymous donors. The Virscan analysis presented in fig. S11 was performed with financial support from Sidra Medicine
Published: 2020

50. Cardiovascular and renal outcomes with empagliflozin in heart failure

Author: Packer, M., Anker, S.D., Butler, J., Filippatos, G., Pocock, S.J., Carson, P., Januzzi, J., Verma, S., Tsutsui, H., Brueckmann, M., Jamal, W., Kimura, K., Schnee, J., Zeller, C., Cotton, D., Bocchi, E., Böhm, M., Choi, D.J., Chopra, V., Chuquiure, E., Giannetti, N., Janssens, S., Zhang, J., Juanatey, J.R. Gonzalez, Kaul, S., Brunner-La Rocca, H.P., Merkely, B., Nicholls, S.J., Perrone, S., Pina, I., Ponikowski, P., Sattar, N., Senni, M., Seronde, M.F., Spinar, J., Squire, I., Taddei, S., Bellersen, L., Wanner, C., Zannad, F., Packer, M, Anker, S, Butler, J, Filippatos, G, Pocock, S, Carson, P, Januzzi, J, Verma, S, Tsutsui, H, Brueckmann, M, Jamal, W, Kimura, K, Schnee, J, Zeller, C, Cotton, D, Bocchi, E, Böhm, M, Choi, D, Chopra, V, Chuquiure, E, Giannetti, N, Janssens, S, Zhang, J, Gonzalez Juanatey, J, Kaul, S, Brunner-La Rocca, H, Merkely, B, Nicholls, S, Perrone, S, Pina, I, Ponikowski, P, Sattar, N, Senni, M, Seronde, M, Spinar, J, Squire, I, Taddei, S, Wanner, C, Zannad, F, Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), and RS: Carim - H02 Cardiomyopathy
Subjects: Male, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], 030204 cardiovascular system & hematology, law.invention, 0302 clinical medicine, Randomized controlled trial, Glucosides, law, Cardiovascular Disease, Medicine, 030212 general & internal medicine, Renal Insufficiency, Chronic, Benzhydryl Compound, Sodium-Glucose Transporter 2 Inhibitor, General Medicine, Stroke volume, Middle Aged, Hospitalization, Cardiovascular Diseases, Disease Progression, Female, Type 2, Human, Glomerular Filtration Rate, medicine.medical_specialty, Glucoside, MEDLINE, Aged, Benzhydryl Compounds, Diabetes Mellitus, Type 2, Double-Blind Method, Heart Failure, Humans, Proportional Hazards Models, Renal Insufficiency, Chronic, Sodium-Glucose Transporter 2 Inhibitors, Stroke Volume, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Internal medicine, Diabetes mellitus, Empagliflozin, Diabetes Mellitus, In patient, business.industry, Proportional hazards model, medicine.disease, Heart failure, Proportional Hazards Model, business
Abstract: Contains fulltext : 230126.pdf (Publisher’s version ) (Open Access) BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure in patients regardless of the presence or absence of diabetes. More evidence is needed regarding the effects of these drugs in patients across the broad spectrum of heart failure, including those with a markedly reduced ejection fraction. METHODS: In this double-blind trial, we randomly assigned 3730 patients with class II, III, or IV heart failure and an ejection fraction of 40% or less to receive empagliflozin (10 mg once daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of cardiovascular death or hospitalization for worsening heart failure. RESULTS: During a median of 16 months, a primary outcome event occurred in 361 of 1863 patients (19.4%) in the empagliflozin group and in 462 of 1867 patients (24.7%) in the placebo group (hazard ratio for cardiovascular death or hospitalization for heart failure, 0.75; 95% confidence interval [CI], 0.65 to 0.86; P
Published: 2020

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