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1. Disconnect between the effects of serelaxin on renal function and outcome in acute heart failure

Author: Beldhuis, I. E., ter Maaten, J. M., Figarska, S. M., Damman, K., Pang, P. S., Greenberg, B., Davison, B. A., Cotter, G., Severin, T., Gimpelewicz, C., Felker, G. M., Filippatos, G., Teerlink, J. R., Metra, M., and Voors, A. A.
Published: 2023
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2. 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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3. Peer Review #2 of "To flea or not to flea: survey of UK companion animal ectoparasiticide usage and activities affecting pathways to the environment (v0.2)"

Author: Teerlink, J, additional
Published: 2023
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4. Mineralocorticoid receptor antagonist initiation during admission is associated with improved outcomes irrespective of ejection fraction in patients with acute heart failure

Author: Beldhuis, I. E., primary, Damman, K., additional, Pang, P.S., additional, Greenberg, B., additional, Davison, B.A., additional, Cotter, G., additional, Gimpelewicz, C., additional, Felker, G. M., additional, Filippatos, G., additional, Teerlink, J. R., additional, Metra, M., additional, Voors, A. A., additional, and ter Maaten, J.M., additional
Published: 2023
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5. Long-Term Effect of Endothelin Receptor Antagonism With Bosentan on the Morbidity and Mortality of Patients With Severe Chronic Heart Failure: Primary Results of the ENABLE Trials

Author: Packer, Milton, Caspi, Avi, Kiowski, Wolfgang, Krum, Henry, Pratt, Craig, Swedberg, Karl, Massie, Barry, McMurray, John, Connally, Eugene, Petrie, Mark, DeMets, David, Anderson, Susan, Barnet, Jody, Cody, Robert, Dargie, Henry, Francis, Gary, Greenberg, Barry, Reichen, Juerg, Karrasch, J., Krum, H., Horowitz, J., Amerena, J., Sindone, A., MacDonald, P., Jeffrey, I., Button, I., DeAngelis, E., Pacher, R., Davies, R., McAlister, F., Tanser, P., Sussex, B., Baumann, G., Fleck, E., Olbrich, H.-G., Werdan, K., Klein, H., Staffeld, F., Zeiher, A.M., Roediger, C., Caspi, A., Marmor, A., Reisin, L., Vered, Z., Klainman, E., Roguin, N., Tzivoni, D., David, D., Lewis, B., Abinader, E., Omary, M., Rosenman, Y., Kaluski, E., Breedveld, R.W., van der Burgh, P.H., Dunselman, P.H.J.M., Schaafsma, H.J., Hertzberger, D.P., Holwerda, N.J., Kragten, J.A., van Wijngaarden, J., Posma, J.L., Said, S.A.M., Slegers, L.C., Tjon Joe Gin, R.M., Wempe, F.N., Wesdorp, J.C.L., Willems, A.R., Withagen, A.J.A.M., Cornel, J.M., van Kempen, L.H.J., Kiowski, W., Bertel, O., Moccetti, T., McMurray, J.J.V., Greenbaum, R.A., Bennett, P., Swan, J., Davies, G., Findlay, I., Gould, B., Ball, S., Hubner, P., Lahiri, A., McLay, J., Northcote, R., Saltissi, S., Squire, I., Stephens, J., Stewart, M., Bridgen, G., Walsh, J., Webb, D.J., Ansari, Z., Baron, S., Bellinger, R., Bennet, W., Benvenuti, D., Dawley, D., Egbujiobi, L.C., Eisenstein, I., Little, T., Hertsberg, A., Greenspan, M., Grossman, R.J., Hanley, P., Jesrani, M., Kashou, H., Levites, R., Malik, R., Marmorstein, B., Schwartz, M., Nisar, A., Perelman, R., Schwarz, M.L., Sedlis, S., Srebro, J., Taveras, M., Weiss, R., Weitzman, P., Wetherley, G.K., El Shahawy, M., Kereiakes, D., Campos, L., Peterson, G., Small, R.S., Davis, W.R., Olivari, M.-T., Meengs, W., Koren, M., Slagona, P., Jennison, S., Hershberger, R., Browne, K.F., Farnham, D.J., Zelenkofske, S., Lawless, C., Nathan, M., Meyer, T., Kukin, M., Parekh, H., Berkowitz, R., Boehmer, J., Brozena, S., Dandona, P., Dec, G.W., DeQuattro, V., Fenster, P., Fowler, M., Ellaham, S., Geller, M., Gheorgiade, M., Ghali, J., Murali, S., Katz, S., Bott-Silverman, C., Singh, B., Thadani, U., Torre, G., Teerlink, J., Chandraratna, T., Kesselbrenner, M., Mukherjee, A., Che-Pin Tsai, C., Abbo, K., Goldberg, M., Smith, T., Martin, R.T., McMurray, John J.V., Massie, Barry M., Pratt, Craig M., Petrie, Mark C., Kobrin, Isaac, and Roux, Sebastien
Published: 2017
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6. 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

7. 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

8. Empagliflozin in Patients Hospitalised for De Novo Versus Decompensated Chronic Heart Failure: Insights From the EMPULSE Trial

Author: Teerlink, J., primary, Voors, A., additional, Collins, S., additional, Kosiborod, M., additional, Biegus, J., additional, Ferreira, J., additional, Nassif, M., additional, Psotka, M., additional, Tromp, J., additional, Blatchford, J., additional, Salsali, A., additional, Kraus, B., additional, Ponikowski, P., additional, and Angermann, C., additional
Published: 2022
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9. 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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10. Blood urea nitrogen to creatinine ratio in the general population and patients with acute heart failure: 1418

Author: Matsue, Y, Van Der Meer, P, Damman, K, Teerlink, J R, Oʼconnor, C M, Bakker, S J, Givertz, M M, Gansevoort, R T, Van Veldhuisen, D J, and Voors, A A
Published: 2016

11. 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

12. 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

13. Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure

Author: Teerlink, J. R., Diaz, R., Michael Felker, G., Mcmurray, J. J. V., Metra, M., Solomon, S. D., Adams, K. F., Anand, I., Arias-Mendoza, A., Biering-Sorensen, T., Bohm, M., Bonderman, D., Cleland, J. G. F., Corbalan, R., Crespo-Leiro, M. G., Dahlstrom, U., Echeverria, L. E., Fang, J. C., Filippatos, G., Fonseca, C., Goncalvesova, E., Goudev, A. R., Howlett, J. G., Lanfear, D. E., Li, J., Lund, M., Ambrosio, G., Carluccio, E., Macdonald, P., Mareev, V., Momomura, S., O'Meara, E., Parkhomenko, A., Ponikowski, P., Ramires, F. J. A., Serpytis, P., Sliwa, K., Spinar, J., Suter, T. M., Tomcsanyi, J., Vandekerckhove, H., Vinereanu, D., Voors, A. A., Yilmaz, M. B., Zannad, F., Sharpsten, L., Legg, J. C., Varin, C., Honarpour, N., Abbasi, S. A., Malik, F. I., Kurtz, C. E., and Cardiovascular Centre (CVC)
Subjects: Cardiac function curve, Male, medicine.medical_specialty, animal structures, Cardiotonic Agents, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Cardiac Myosins, Internal medicine, medicine, 80 and over, Humans, Urea, 030212 general & internal medicine, Aged, Aged, 80 and over, Heart Failure, Ejection fraction, business.industry, Cardiac myosin, Stroke Volume, General Medicine, Stroke volume, Middle Aged, medicine.disease, R1, Myocardial Contraction, 3. Good health, Omecamtiv mecarbil, Cardiovascular Diseases, Heart failure, cardiovascular system, Cardiology, Female, business, Heart Failure, Systolic, Systolic
Abstract: From: New England Journal of Medicine, Teerlink, JR, Diaz, R, Felker, G, et al. Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure, 384(2):105-116. Copyright © 2020. Massachusetts Medical Society. Reprinted with permission. [Abstract] BACKGROUND. The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS. We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS. During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P=0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro–B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS. Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016-002299-28.)
Published: 2020

14. Effect of Nesiritide in Patients with Acute Decompensated Heart Failure

Author: OʼConnor, C. M., Starling, R. C., Hernandez, A. F., Armstrong, P. W., Dickstein, K., Hasselblad, V., Heizer, G. M., Komajda, M., Massie, B. M., McMurray, J. J.V., Nieminen, M. S., Reist, C. J., Rouleau, J. L., Swedberg, K., Adams, K. F., Jr., Anker, S. D., Atar, D., Battler, A., Botero, R., Bohidar, N. R., Butler, J., Clausell, N., Corbalán, R., Costanzo, M. R., Dahlstrom, U., Deckelbaum, L. I., Diaz, R., Dunlap, M. E., Ezekowitz, J. A., Feldman, D., Felker, G. M., Fonarow, G. C., Gennevois, D., Gottlieb, S. S., Hill, J. A., Hollander, J. E., Howlett, J. G., Hudson, M. P., Kociol, R. D., Krum, H., Laucevicius, A., Levy, W. C., Méndez, G. F., Metra, M., Mittal, S., Oh, B.-H., Pereira, N. L., Ponikowski, P., Wilson, W. H., Tanomsup, S., Teerlink, J. R., Triposkiadis, F., Troughton, R. W., Voors, A. A., Whellan, D. J., Zannad, F., and Califf, R. M.
Published: 2011

15. Effects of serelaxin in patients with acute heart failure

Author: Metra, M., Teerlink, J. R., Cotter, G., Davison, B. A., Felker, G. M., Filippatos, G., Greenberg, B. H., Pang, P. S., Ponikowski, P., Voors, A. A., Adams, K. F., Anker, S. D., Arias-Mendoza, A., Avendano, P., Bacal, F., Bohm, M., Bortman, G., Cleland, J. G. F., Cohen-Solal, A., Crespo-Leiro, M. G., Dorobantu, M., Echeverria, L. E., Ferrari, R., Goland, S., Goncalvesova, E., Goudev, A., Kober, L., Lema-Osores, J., Levy, P. D., Mcdonald, K., Manga, P., Merkely, B., Mueller, C., Pieske, B., Silva-Cardoso, J., Spinar, J., Squire, I., Stepinska, J., Van Mieghem, W., Von Lewinski, D., Wikstrom, G., Yilmaz, M. B., Hagner, N., Holbro, T., Hua, T. A., Sabarwal, S. V., Severin, T., Szecsody, P., Gimpelewicz, C, Lembo, G, and Cardiovascular Centre (CVC)
Subjects: Male, Vasodilator Agents, Vasodilation, Blood Pressure, 030204 cardiovascular system & hematology, NESIRITIDE, THERAPY, law.invention, 0302 clinical medicine, Randomized controlled trial, law, 030212 general & internal medicine, Treatment Failure, Acute Disease, Aged, Cardiovascular Diseases, Disease Progression, Double-Blind Method, Female, Heart Failure, Hospitalization, Humans, Incidence, Infusions, Intravenous, Recombinant Proteins, Relaxin, OUTCOMES, General Medicine, ASSOCIATION, ADMISSION, INSIGHTS, Cardiology, SUBSEQUENT MORTALITY, Intravenous, hormones, hormone substitutes, and hormone antagonists, medicine.drug, medicine.medical_specialty, Infusions, NO, 03 medical and health sciences, Serelaxin, Internal medicine, medicine, In patient, Nesiritide, Pregnancy, business.industry, medicine.disease, PROTECT, Heart failure, RELAX-AHF, business, Hormone
Abstract: BackgroundSerelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure.MethodsIn this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 mu g per kilogram of body weight per day) or placebo, in addition to standard care. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days.ResultsA total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7%) in the serelaxin group and in 290 of the 3271 patients (8.9%) in the placebo group (hazard ratio, 0.98; 95% confidence interval [CI], 0.83 to 1.15; P=0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9%) in the serelaxin group and in 252 (7.7%) in the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P=0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups.ConclusionsIn this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days than placebo. (Funded by Novartis Pharma; RELAX-AHF-2 ClinicalTrials.gov number, NCT01870778.)In a randomized trial, 6545 patients with acute heart failure were assigned to either serelaxin or placebo in addition to standard care. There were no significant differences between the two groups in the incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days.
Published: 2019

16. 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.D. Butler, J. Filippatos, G.S. Jamal, W. Salsali, A. Schnee, J. Kimura, K. Zeller, C. George, J. Brueckmann, M. Zannad, F. Packer, M. Packer, M. Butler, J. Filippatos, G.S. Zannad, F. George, J. Brueckmann, M. Perrone, S. Nicholls, S. Janssens, S. Bocchi, E. Giannetti, N. Verma, S. Jian, Z. Gomez Mesa, J.E. Spinar, J. Böhm, 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. Butler, J. 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. Januzzi, J. Kaul, S. Ping, C.L.S. Lip, G. Marx, N. McCullough, P. Mehta, C. Rosenstock, J. Sattar, N. Scirica, B. Tsutsui, H. Wanner, C. Welty, F.K. Parhofer, K.G. Clayton, T. Pedersen, T.R. Lees, K.R. Konstam, M.A. Greenberg, B. Palmer, M. the EMPEROR-Preserved Trial Committees Investigators
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 meaningful impact on the course of HFpEF, a disorder for which there are currently few therapeutic options. © 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology
Published: 2019

17. 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. Butler, J. Zannad, F. George, J. Brueckmann, M. Perrone, S. Nicholls, S. Janssens, S. Bocchi, E. Giannetti, N. Verma, S. Jian, Z. Spinar, J. Seronde, M.-F. Böhm, 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. Butler, J. 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. Januzzi, J. Kaul, S. Ping, C.L.S. Lip, G. Marx, N. McCullough, P. Mehta, C. Rosenstock, J. Sattar, N. Scirica, B. Tsutsui, H. Wanner, C. Welty, F.K. Parhofer, K.G. Clayton, T. Pedersen, T.R. Lees, K.R. Konstam, M.A. Greenberg, B. Palmer, M. the EMPEROR-Reduced Trial Committees Investigators Executive Committee National Coordinators Consulting Statistician Clinical Events Committee Scientific Excellence Committee Data Monitoring Committee
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 addition of empagliflozin can add meaningfully to current approaches that have established benefits in the treatment of chronic heart failure with left ventricular systolic dysfunction. © 2019 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
Published: 2019

18. P3522Vagus nerve stimulation for chronic heart failure: differences in therapy delivery and clinical efficacy in ANTHEM-HF, INOVATE-HF, and NECTAR-HF

Author: Anand, I, primary, Konstam, M, additional, Udelson, J, additional, Butler, J, additional, Klein, H, additional, Parker, J, additional, Teerlink, J, additional, Libbus, I, additional, Amurthur, B, additional, Kenknight, B, additional, Ardell, J, additional, Gregory, D, additional, Massaro, J, additional, and Dicarlo, L, additional
Published: 2019
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19. 4329Mega-studies in heart failure, effect dilution in examination of new therapies

Author: Cotter, O, primary, Davison, B A, additional, Koch, G, additional, Senger, S, additional, Metra, M, additional, Voors, A A, additional, Mebazza, A, additional, Nielsen, O W, additional, Chioncel, O, additional, Pang, P, additional, Greenberg, B H, additional, Maggioni, A, additional, Sato, N, additional, Teerlink, J R, additional, and Cotter, G, additional
Published: 2019
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20. Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure.

Author: Teerlink, J. R., Diaz, R., Felker, G. M., McMurray, J. J. V., Metra, M., Solomon, S. D., Adams, K. F., Anand, I., Arias-Mendoza, A., Biering-Sorensen, T., Bohm, M., Bonderman, D., Cleland, J. G. F., Corbalan, R., Crespo-Leiro, M. G., Dahlstrom, U., Echeverria, L. E., Fang, J. C., Filippatos, G., and Fonseca, C.
Subjects: *HEART failure, *HEART failure patients, *MYOSIN, *VENTRICULAR arrhythmia, *PERIPARTUM cardiomyopathy, *TROPONIN I, *CARDIAC patients
Abstract: BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P=0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016-002299-28.). [ABSTRACT FROM AUTHOR]
Published: 2021
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21. Acute Treatment With Omecamtiv Mecarbil to Increase Contractility in Acute Heart Failure : The ATOMIC-AHF Study

Author: Teerlink, J, Felker, M, McMurray, J, Ponikowski, P, Metra, M, Filippatos, G, Ezekowitz, J, Dickstein, K, Cleland, JGF, Kim, J, Lei, L, Knusel, B, Wolff, A, Malik, F, Wasserman, S, and ATOMIC-AHF Investigators
Subjects: 1117 Public Health And Health Services, inotrope, cardiac myosin activator, dyspnea, arrhythmia, 1102 Cardiovascular Medicine And Haematology
Published: 2016

22. Angiotensin Receptor Neprilysin Inhibition Compared With Enalapril on the Risk of Clinical Progression in Surviving Patients With Heart Failure

Author: Packer, M, Mcmurray, J, Desai, A, Gong, J, Lefkowitz, M, Rizkala, A, Rouleau, J, Shi, V, Solomon, S, Swedberg, K, Zile, M, Andersen, K, Arango, J, Arnold, J, Belohlavek, J, Bohm, M, Boytsov, S, Burgess, L, Cabrera, W, Calvo, C, Chen, C, Dukat, A, Duarte, Y, Erglis, A, Fu, M, Gomez, E, Gonzalez-Medina, A, Hagege, A, Huang, J, Katova, T, Kiatchoosakun, S, Kim, K, Kozan, O, Llamas, E, Martinez, F, Merkely, B, Mendoza, I, Mosterd, A, Negrusz-Kawecka, M, Peuhkurinen, K, Ramires, F, Refsgaard, J, Rosenthal, A, Senni, M, Jr, A, Silva-Cardoso, J, Squire, I, Starling, R, Teerlink, J, Vanhaecke, J, Vinereanu, D, Wong, R, Packer M, McMurray JJV, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile M, Andersen K, Arango JL, Arnold JM, Belohlavek J, Bohm M, Boytsov S, Burgess LJ, Cabrera W, Calvo C, Chen CH, Dukat A, Duarte YC, Erglis A, Fu M, Gomez E, Gonzalez-Medina A, Hagege AA, Huang J, Katova T, Kiatchoosakun S, Kim KS, Kozan O, Llamas EB, Martinez F, Merkely B, Mendoza I, Mosterd A, Negrusz-Kawecka M, Peuhkurinen K, Ramires FJA, Refsgaard J, Rosenthal A, Senni M, Jr ASS, Silva-Cardoso J, Squire IB, Starling RC, Teerlink JR, Vanhaecke J, Vinereanu D, Wong RCC, Packer, M, Mcmurray, J, Desai, A, Gong, J, Lefkowitz, M, Rizkala, A, Rouleau, J, Shi, V, Solomon, S, Swedberg, K, Zile, M, Andersen, K, Arango, J, Arnold, J, Belohlavek, J, Bohm, M, Boytsov, S, Burgess, L, Cabrera, W, Calvo, C, Chen, C, Dukat, A, Duarte, Y, Erglis, A, Fu, M, Gomez, E, Gonzalez-Medina, A, Hagege, A, Huang, J, Katova, T, Kiatchoosakun, S, Kim, K, Kozan, O, Llamas, E, Martinez, F, Merkely, B, Mendoza, I, Mosterd, A, Negrusz-Kawecka, M, Peuhkurinen, K, Ramires, F, Refsgaard, J, Rosenthal, A, Senni, M, Jr, A, Silva-Cardoso, J, Squire, I, Starling, R, Teerlink, J, Vanhaecke, J, Vinereanu, D, Wong, R, Packer M, McMurray JJV, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile M, Andersen K, Arango JL, Arnold JM, Belohlavek J, Bohm M, Boytsov S, Burgess LJ, Cabrera W, Calvo C, Chen CH, Dukat A, Duarte YC, Erglis A, Fu M, Gomez E, Gonzalez-Medina A, Hagege AA, Huang J, Katova T, Kiatchoosakun S, Kim KS, Kozan O, Llamas EB, Martinez F, Merkely B, Mendoza I, Mosterd A, Negrusz-Kawecka M, Peuhkurinen K, Ramires FJA, Refsgaard J, Rosenthal A, Senni M, Jr ASS, Silva-Cardoso J, Squire IB, Starling RC, Teerlink JR, Vanhaecke J, Vinereanu D, and Wong RCC
Abstract: Background-Clinical trials in heart failure have focused on the improvement in symptoms or decreases in the risk of death and other cardiovascular events. Little is known about the effect of drugs on the risk of clinical deterioration in surviving patients. Methods and Results-We compared the angiotensin-neprilysin inhibitor LCZ696 (400 mg daily) with the angiotensinconverting enzyme inhibitor enalapril (20 mg daily) in 8399 patients with heart failure and reduced ejection fraction in a double-blind trial. The analyses focused on prespecified measures of nonfatal clinical deterioration. In comparison with the enalapril group, fewer LCZ696-treated patients required intensification of medical treatment for heart failure (520 versus 604; hazard ratio, 0.84; 95% confidence interval, 0.74-0.94; P=0.003) or an emergency department visit for worsening heart failure (hazard ratio, 0.66; 95% confidence interval, 0.52-0.85; P=0.001). The patients in the LCZ696 group had 23% fewer hospitalizations for worsening heart failure (851 versus 1079; P<0.001) and were less likely to require intensive care (768 versus 879; 18% rate reduction, P=0.005), to receive intravenous positive inotropic agents (31% risk reduction, P<0.001), and to have implantation of a heart failure device or cardiac transplantation (22% risk reduction, P=0.07). The reduction in heart failure hospitalization with LCZ696 was evident within the first 30 days after randomization. Worsening of symptom scores in surviving patients was consistently more common in the enalapril group. LCZ696 led to an early and sustained reduction in biomarkers of myocardial wall stress and injury (N-terminal pro-Btype natriuretic peptide and troponin) versus enalapril. Conclusions-Angiotensin-neprilysin inhibition prevents the clinical progression of surviving patients with heart failure more effectively than angiotensin-converting enzyme inhibition.
Published: 2015

23. A putative placebo analysis of the effects of LCZ696 on clinical outcomes in heart failure

Author: Mcmurray, J, Packer, M, Desai, A, Gong, J, Greenlaw, N, Lefkowitz, M, Rizkala, A, Shi, V, Rouleau, J, Solomon, S, Swedberg, K, Zile, M, Andersen, K, Arango, J, Arnold, M, Belohlavek, J, Bohm, M, Boytsov, S, Burgess, L, Cabrera, W, Chen, C, Erglis, A, Fu, M, Gomez, E, Gonzalez, A, Hagege, A, Katova, T, Kiatchoosakun, S, Kim, K, Bayram, E, Martinez, F, Merkely, B, Mendoza, I, Mosterd, A, Negrusz-Kawecka, M, Peuhkurinen, K, Ramires, F, Refsgaard, J, Senni, M, Sibulo, A, Silva-Cardoso, J, Squire, I, Starling, R, Vinereanu, D, Teerlink, J, Wong, R, McMurray J, Packer M, Desai A, Gong JJ, Greenlaw N, Lefkowitz M, Rizkala A, Shi V, Rouleau J, Solomon S, Swedberg K, Zile MR, Andersen K, Arango JL, Arnold M, Belohlavek J, Bohm M, Boytsov S, Burgess L, Cabrera W, Chen CH, Erglis A, Fu M, Gomez E, Gonzalez A, Hagege AA, Katova T, Kiatchoosakun S, Kim KS, Bayram E, Martinez F, Merkely B, Mendoza I, Mosterd A, Negrusz-Kawecka M, Peuhkurinen K, Ramires F, Refsgaard J, Senni M, Sibulo AS, Silva-Cardoso J, Squire I, Starling RC, Vinereanu D, Teerlink JR, Wong R, Mcmurray, J, Packer, M, Desai, A, Gong, J, Greenlaw, N, Lefkowitz, M, Rizkala, A, Shi, V, Rouleau, J, Solomon, S, Swedberg, K, Zile, M, Andersen, K, Arango, J, Arnold, M, Belohlavek, J, Bohm, M, Boytsov, S, Burgess, L, Cabrera, W, Chen, C, Erglis, A, Fu, M, Gomez, E, Gonzalez, A, Hagege, A, Katova, T, Kiatchoosakun, S, Kim, K, Bayram, E, Martinez, F, Merkely, B, Mendoza, I, Mosterd, A, Negrusz-Kawecka, M, Peuhkurinen, K, Ramires, F, Refsgaard, J, Senni, M, Sibulo, A, Silva-Cardoso, J, Squire, I, Starling, R, Vinereanu, D, Teerlink, J, Wong, R, McMurray J, Packer M, Desai A, Gong JJ, Greenlaw N, Lefkowitz M, Rizkala A, Shi V, Rouleau J, Solomon S, Swedberg K, Zile MR, Andersen K, Arango JL, Arnold M, Belohlavek J, Bohm M, Boytsov S, Burgess L, Cabrera W, Chen CH, Erglis A, Fu M, Gomez E, Gonzalez A, Hagege AA, Katova T, Kiatchoosakun S, Kim KS, Bayram E, Martinez F, Merkely B, Mendoza I, Mosterd A, Negrusz-Kawecka M, Peuhkurinen K, Ramires F, Refsgaard J, Senni M, Sibulo AS, Silva-Cardoso J, Squire I, Starling RC, Vinereanu D, Teerlink JR, and Wong R
Abstract: Aims Although active-controlled trials with renin-angiotensin inhibitors are ethically mandated in heart failure with reduced ejection fraction, clinicians and regulators often want to know how the experimental therapy would perform compared with placebo. The angiotensin receptor-neprilysin inhibitor LCZ696 was compared with enalapril in PARADIGM-HF. We made indirect comparisons of the effects of LCZ696 with putative placebos. Methods and results We used the treatment-armof the Studies OfLeftVentricularDysfunction(SOLVD-T) as the reference trial for comparison of an ACE inhibitor to placebo and the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity-Alternative trial (CHARM-Alternative) as the reference trial for comparison of an ARB to placebo. The hazard ratio of LCZ696vs. aputativeplacebowasestimatedthroughtheproductof the hazardratioofLCZ696vs. enalapril (active-control) and that of the historical active-control (enalapril or candesartan) vs. placebo. For the primary composite outcome of cardiovascular death or heart failure hospitalization in PARADIGM-HF, the relative risk reduction with LCZ696 vs. a putative placebo from SOLVD-T was 43% (95%CI 34-50%; P< 0.0001) with similarly large effects on cardiovascular death (34%, 21-44%; P< 0.0001) and heart failure hospitalization (49%, 39-58%; P< 0.0001). For all-cause mortality, the reduction comparedwith a putative placebowas 28% (95%CI 15-39%; P< 0.0001). Putative placebo analyses based onCHARM-Alternative gave relative risk reductions of 39% (95%CI 27-48%; P< 0.0001) for the composite outcome of cardiovascular death or heart failure hospitalization, 32% (95%CI 16-45%; P< 0.0001) for cardiovascular death, 46% (33-56%; P< 0.0001) for heart failure hospitalization, and 26% (95%CI 11-39%; P< 0.0001) for all-cause mortality. Conclusion These indirect comparisons of LCZ696 with a putative placebo show that the strategy of combined angiotensin receptor blockade and nep
Published: 2015

24. Developing Therapies for Heart Failure With Preserved Ejection Fraction Current State and Future Directions

Author: Butler, J, Fonarow, G, Zile, M, Lam, C, Roessig, L, Schelbert, E, Shah, S, Ahmed, A, Bonow, R, Cleland, J, Cody, R, Chioncel, O, Collins, S, Dunnmon, P, Filippatos, G, Lefkowitz, M, Marti, C, Mcmurray, J, Misselwitz, F, Nodari, S, O'Connor, C, Pfeffer, M, Pieske, B, Pitt, B, Rosano, G, Sabbah, H, Senni, M, Solomon, S, Stockbridge, N, Teerlink, J, Georgiopoulou, V, Gheorghiade, M, Butler J, Fonarow GC, Zile MR, Lam CS, Roessig L, Schelbert EB, Shah SJ, Ahmed A, Bonow RO, Cleland JGF, Cody RJ, Chioncel O, Collins SP, Dunnmon P, Filippatos G, Lefkowitz MP, Marti CN, McMurray JJ, Misselwitz F, Nodari S, O'Connor C, Pfeffer MA, Pieske B, Pitt B, Rosano G, Sabbah HN, Senni M, Solomon SD, Stockbridge N, Teerlink JR, Georgiopoulou VV, Gheorghiade M, Butler, J, Fonarow, G, Zile, M, Lam, C, Roessig, L, Schelbert, E, Shah, S, Ahmed, A, Bonow, R, Cleland, J, Cody, R, Chioncel, O, Collins, S, Dunnmon, P, Filippatos, G, Lefkowitz, M, Marti, C, Mcmurray, J, Misselwitz, F, Nodari, S, O'Connor, C, Pfeffer, M, Pieske, B, Pitt, B, Rosano, G, Sabbah, H, Senni, M, Solomon, S, Stockbridge, N, Teerlink, J, Georgiopoulou, V, Gheorghiade, M, Butler J, Fonarow GC, Zile MR, Lam CS, Roessig L, Schelbert EB, Shah SJ, Ahmed A, Bonow RO, Cleland JGF, Cody RJ, Chioncel O, Collins SP, Dunnmon P, Filippatos G, Lefkowitz MP, Marti CN, McMurray JJ, Misselwitz F, Nodari S, O'Connor C, Pfeffer MA, Pieske B, Pitt B, Rosano G, Sabbah HN, Senni M, Solomon SD, Stockbridge N, Teerlink JR, Georgiopoulou VV, and Gheorghiade M
Abstract: The burden of heart failure with preserved ejection fraction (HFpEF) is considerable and is projected to worsen. To date, there are no approved therapies available for reducing mortality or hospitalizations for these patients. The pathophysiology of HFpEF is complex and includes alterations in cardiac structure and function, systemic and pulmonary vascular abnormalities, end-organ involvement, and comorbidities. There remain major gaps in our understanding of HFpEF pathophysiology. To facilitate a discussion of how to proceed effectively in future with development of therapies for HFpEF, a meeting was facilitated by the Food and Drug Administration and included representatives from academia, industry, and regulatory agencies. This document summarizes the proceedings from this meeting.
Published: 2014

25. Abstract 18883: High Sensitivity Troponin T in Acute Heart Failure: Insights from RELAX-AHF

Author: Felker, G. Michael, primary, Mentz, Robert J, additional, Teerlink, J R, additional, Voors, A A, additional, Pang, P S, additional, Ponikowski, P, additional, Greenberg, B H, additional, Filippatos, G, additional, Davison, B A, additional, Cotter, G, additional, Prescott, M F, additional, Hua, T, additional, Severin, T, additional, and Metra, M, additional
Published: 2014
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26. Diuretic response in acute heart failure: clinical characteristics and prognostic significance

Author: Valente, M. A. E., primary, Voors, A. A., additional, Damman, K., additional, Van Veldhuisen, D. J., additional, Massie, B. M., additional, O'Connor, C. M., additional, Metra, M., additional, Ponikowski, P., additional, Teerlink, J. R., additional, Cotter, G., additional, Davison, B., additional, Cleland, J. G. F., additional, Givertz, M. M., additional, Bloomfield, D. M., additional, Fiuzat, M., additional, Dittrich, H. C., additional, and Hillege, H. L., additional
Published: 2014
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27. Serelaxin in acute heart failure patients with preserved left ventricular ejection fraction: results from the RELAX-AHF trial

Author: Filippatos, G., primary, Teerlink, J. R., additional, Farmakis, D., additional, Cotter, G., additional, Davison, B. A., additional, Felker, G. M., additional, Greenberg, B. H., additional, Hua, T., additional, Ponikowski, P., additional, Severin, T., additional, Unemori, E., additional, Voors, A. A., additional, and Metra, M., additional
Published: 2013
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28. Omecamtiv Mecarbil: Phase 2 Study Shows No Improvement in Dyspnea AHF But Trend for Further Exploration

Author: Rizzo, T., primary and Teerlink, J. R., additional
Published: 2013
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29. Effects of serelaxin in subgroups of patients with acute heart failure: results from RELAX-AHF

Author: Metra, M., primary, Ponikowski, P., additional, Cotter, G., additional, Davison, B. A., additional, Felker, G. M., additional, Filippatos, G., additional, Greenberg, B. H., additional, Hua, T. A., additional, Severin, T., additional, Unemori, E., additional, Voors, A. A., additional, and Teerlink, J. R., additional
Published: 2013
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30. Association of segmental wall motion abnormalities occurring during hemodialysis with post-dialysis fatigue

Author: Dubin, R. F., primary, Teerlink, J. R., additional, Schiller, N. B., additional, Alokozai, D., additional, Peralta, C. A., additional, and Johansen, K. L., additional
Published: 2013
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31. Serelaxin as a Novel Treatment for Acute Heart Failure: Results of the RELAX-AHF Trial

Author: Vinall, P., primary and Teerlink, J. R., additional
Published: 2012
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32. Age, Clinical Characteristics and Outcomes of Patients With Acute Decompensated Heart Failure: Insights from the PROTECT Trial

Author: Metra, M., primary, Chiswell, K., additional, Fiuzat, M., additional, Lazzarini, V., additional, Horton, J., additional, Davison, B., additional, Cleland, J., additional, Ponikowski, P., additional, Teerlink, J., additional, Voors, A., additional, Givertz, M., additional, Mansoor, G., additional, Massie, B., additional, Cotter, G., additional, and O'Connor, C., additional
Published: 2012
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33. Cardiac inotropes: current agents and future directions

Author: Hasenfuss, G., primary and Teerlink, J. R., additional
Published: 2011
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34. Early dyspnoea relief in acute heart failure: prevalence, association with mortality, and effect of rolofylline in the PROTECT Study

Author: Metra, M., primary, O'Connor, C. M., additional, Davison, B. A., additional, Cleland, J. G. F., additional, Ponikowski, P., additional, Teerlink, J. R., additional, Voors, A. A., additional, Givertz, M. M., additional, Mansoor, G. A., additional, Bloomfield, D. M., additional, Jia, G., additional, DeLucca, P., additional, Massie, B., additional, Dittrich, H., additional, and Cotter, G., additional
Published: 2011
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35. Relaxin Reduces Dyspnea, Cardiovascular Death, and Rehospitalization in Acute Heart Failure

Author: Jacobson, A., primary and Teerlink, J. R., additional
Published: 2009
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36. First clinical trial of the selective cardiac myosin activator, CK-1827452, in Heart Failure: effect of dose and plasma concentration on systolic function

Author: CLELAND, J, primary, MCMURRAY, J, additional, LANG, C, additional, CLARKE, C, additional, NEYSES, L, additional, SAIKALI, K, additional, LEE, J, additional, GOLDMAN, J, additional, TEERLINK, J, additional, and MALIK, F, additional
Published: 2008
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37. 477 Patient self-assessments of heart failure status using either categorical or continuous scales were highly correlated in REVIVE IandII

Author: TEERLINK, J, primary, THAKKAR, R, additional, SALON, J, additional, HUANG, B, additional, and PADLEY, R, additional
Published: 2007
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38. 486 Clinical composite endpoint classification of REVIVE II corresponds to all-cause mortality risk

Author: TEERLINK, J, primary, DELGADOHERRERA, L, additional, THAKKAR, R, additional, HUANG, B, additional, and PADLEY, R, additional
Published: 2007
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39. The ADHERE classification and regression tree model overestimates mortality rates in clinical trials: results from REVIVE I & II

Author: Thakkar, R, primary, Teerlink, J, additional, Colucci, W, additional, Young, J, additional, and Massie, B, additional
Published: 2007
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40. A NEW RADIO-FREQUENCY HEATING DEVICE SHRINKS CHRONIC LEFT VENTRICULAR MYOCARDIAL INFARCT AREA

Author: Wadhwani, S, primary, Ratcliffe, M B, additional, Wallace, A W, additional, Salahieh, A, additional, Hong, J, additional, Sung, S, additional, and Teerlink, J R, additional
Published: 1999
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41. The Prognostic Significance of Valvular Abnormalities in Patients With Severe Left Ventricular Dysfunction

Author: Teerlink, J, primary
Published: 1998
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42. Increased Expression of Human Cu-Zn Superoxide Dismutase in a Transgenic Mouse Model of Ischemia/reperfusion

Author: Teerlink, J, primary
Published: 1998
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43. Role of endogenous endothelin in normal hemodynamic status of anesthetized dogs

Author: Teerlink, J. R., primary, Carteaux, J. P., additional, Sprecher, U., additional, Loffler, B. M., additional, Clozel, M., additional, and Clozel, J. P., additional
Published: 1995
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44. Role of endothelin in the maintenance of blood pressure in conscious rats with chronic heart failure. Acute effects of the endothelin receptor antagonist Ro 47-0203 (bosentan).

Author: Teerlink, J R, primary, Löffler, B M, additional, Hess, P, additional, Maire, J P, additional, Clozel, M, additional, and Clozel, J P, additional
Published: 1994
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45. Progressive ventricular remodeling in response to diffuse isoproterenol-induced myocardial necrosis in rats.

Author: Teerlink, J R, primary, Pfeffer, J M, additional, and Pfeffer, M A, additional
Published: 1994
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46. Increased vascular responsiveness to norepinephrine in rats with heart failure is endothelium dependent. Dissociation of basal and stimulated nitric oxide release.

Author: Teerlink, J R, primary, Gray, G A, additional, Clozel, M, additional, and Clozel, J P, additional
Published: 1994
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47. Potent vasoconstriction mediated by endothelin ETB receptors in canine coronary arteries.

Author: Teerlink, J R, primary, Breu, V, additional, Sprecher, U, additional, Clozel, M, additional, and Clozel, J P, additional
Published: 1994
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48. Hemodynamic variability and circadian rhythm in rats with heart failure: role of locomotor activity

Author: Teerlink, J. R., primary and Clozel, J. P., additional
Published: 1993
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49. A Low baseline hsTnT value in acute heart failure identifies patients at very low risk for 180-day cardiovascular mortality: An analysis from the RELAX-AHF trial

Author: Pang, P., Metra, M., Prescott, M. F., Piotr Ponikowski, Kriger, J., Greenberg, B., Filippatos, G., Felker, M., Davison, B., and Teerlink, J. R.

50. Dyspnea relief with serelaxin-treatment in patients with acute heart failure in the RELAX-AHF trial: the earlier the better?

Author: Teerlink, J. R., Metra, M., Cotter, G., Davison, B. A., Felker, G. M., Filippatos, G. M., Greenberg, B. H., Piotr Ponikowski, Voors, A. A., and Unemori, E.

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