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1. Usefulness of a refined computed tomography imaging method to assess the prevalence of residual pulmonary thrombi in patients 1 year after acute pulmonary embolism: The Nagoya PE study

Author: Nakano, Yoshihisa, Adachi, Shiro, Nishiyama, Itsumure, Yasuda, Kenichiro, Imai, Ryo, Yoshida, Masahiro, Iwano, Shingo, Kondo, Takahisa, Murohara, Toyoaki, Ando, M., Izawa, H., Okumura, N., Watanabe, E., Tsutsumi, Y., Shinoda, M., Tatami, Y., Oguri, M., Tomita, Y., Yamamoto, T., Ishiki, R., Kobayashi, K., Kawaguchi, K., Suzuki, S., Shimizu, K., Oshima, S., Kamiya, H., Kada, K., Sakai, S., Akaboshi, M., Ohno, O., Kimura, A., Mitani, Y., Watarai, M., Kobayashi, S., Tsuboi, H., Tanaka, T., Miura, M., Mokuno, S., Kondo, T., Yumiko, Y., Muto, M., Takada, Y., Ajioka, M., Shimizu, A., Kaneshiro, M., Ohno, J., Makino, M., Matsui, H., Shumiya, T., Harada, S., Hayashi, K., Awaji, Y., Somura, F., Yoshida, Y., Matsubara, K., Nishimura, H., and Morikawa, S.
Published: 2022
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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
Full Text: View/download PDF

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

Author: 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, 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Published: 2022
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4. Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI): a phase 3, placebo-controlled, randomised trial

Author: Bhatt, D, Steg, P, Mehta, S, Leiter, L, Simon, T, Fox, K, Held, C, Andersson, M, Himmelmann, A, Ridderstrale, W, Chen, J, Song, Y, Diaz, R, Goto, S, James, S, Ray, K, Parkhomenko, A, Kosiborod, M, Mcguire, D, Harrington, R, Santos, V, Jain, A, Lendel, I, Russo, M, Haught, W, Bouza, M, Gogia, H, Banerjee, S, Kichura, G, Kantaros, L, Padron, F, Passi, R, Stone, J, Pursley, M, D'Urso, M, Gardner, T, Bennett, J, Nour, K, Saini, S, Zhang, W, Kumbhani, D, Thomas, D, Angiolillo, D, Bertolet, B, Roman-Miranda, A, Black, R, Manshadi, R, Vaca, C, Blanco, A, Napoli, M, Brabham, D, Akyea-Djamson, A, Desai, P, Prasada, S, Khaira, A, Forgosh, L, Lieber, I, Umpierrez, G, Singal, D, Londono, J, Fraser, N, Ruiz, J, Vega, D, Rodriguez, L, Brown, C, Syed, F, Aggarwala, G, Eaves, W, Foster, M, Gupta, D, Avino, D, Asfour, W, Tonnessen, G, Zhao, X, Singh, N, Brockmyre, A, Lepor, N, Shammas, N, Blick, D, Hearne, S, Prodafikas, J, Carell, E, Izzo, M, Karim, A, Zakhary, B, Atieh, M, Leichter, S, Meadows, C, Hotchkiss, D, Abu-Fadel, M, Wiseman, A, Bander, J, Shah, M, Ganim, R, Sopko, K, Khan, M, Lloret, R, Weirick, T, Mehta, R, Thadani, U, Bhargava, A, Moya, J, Staniloae, C, Guerra, Y, Chhabra, A, Kosmicki, D, Shaheen, W, Mohammed, A, Bitters, J, Pattanayak, J, Javier, J, Srivastava, S, Phillips, R, Al-Amin, J, Lillestol, M, Simpson, P, Hazan, L, Amin, A, Shah, G, Korpas, D, Platt, B, Dickert, J, Puente, O, Hiotis, L, Doyle, T, Rajan, R, Meholick, A, Gring, C, Hage-Korban, E, Feldman, R, Colfer, H, Butman, S, Hart, T, Huling, R, Eshaghian, S, Quintana, O, Cheung, D, Handel, F, Rodriguez, M, Suh, D, Gordon, P, Pressman, G, Bauer, M, French, W, Barettella, M, Chatrathi, S, Suresh, D, Goldberg, R, Huth, M, Younis, L, Rahman, A, Mascolo, R, Welch, M, Suneja, R, Smith, S, Shurmur, S, Agaiby, J, Jingo, A, Johnston, J, Beth, M, Vlastaris, A, Kemp, S, Taheri, H, Pereira, E, Deyoung, M, Hawa, Z, Smith, R, Galski, T, Garas, S, Reddy, M, Sharma, S, Hargrove, J, Treasure, C, Emerson, R, 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Schmedtje, J, Nadar, V, Graham, B, Labroo, A, Clavijo, L, Roseman, H, Ledesma, G, Rosen, R, Dor, I, Kirby, W, Sutton, J, Eder, F, Iteld, B, Gomez-Cortes, J, Buchbinder, M, Kasper, J, Terrelonge, A, Torres, G, Jagielo, T, Alvarez, J, Handelsman, Y, Guillen, M, Richwine, R, Lewy-Alterbaum, L, Corder, C, Arvind, M, Bolshoun, D, Mikhail, M, Minton, S, Alvarado, O, Abbott, J, Cauthen, B, Welter, R, Mintz, R, Cox, J, Quick, A, Weiss, M, Dy, J, Zebrack, J, Gandelman, G, Hegde, V, Silver, M, Degregorio, M, Lawson, W, Paa, C, Bortnick, A, Krolick, M, Sotolongo, R, Cheirif, J, Kumar, P, Jetty, P, Patel, A, Kruk, M, Kobielusz-Gembala, I, Rewerska, B, Madrzejewski, A, Milewski, K, Cygler, J, Petryka-Mazurkiewicz, J, Jastrzebski, W, Korecki, J, Fil, W, Prokopczuk, J, Bochenek, A, Wujkowski, M, Witek, R, Konczakowski, P, Miekus, P, Szczasny, M, Musial, W, Cymerman, K, Lampart, J, Mikosinski, J, Szynal, S, Fares, I, Opolski, G, Mazur, S, Wozakowska-Kaplon, B, Bijata-Bronisz, R, Wierucki, L, Losa, B, 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C., Ferrario M., Assanelli E., Senni M., Piatti P., Calabro P., Urbinati S., Michisanti M., Varbella F., de Cosmo S., Trevisan R., Bellotti S., Di Pasquale G., Bongo A. S., Uguccioni M., Mannucci E., Mauro C., Ragonese M., Fresco C., Turturo M., Marcucci R., Lievano Triana M. J., Arana C., Accini J., Botero R., Muzyk-Osikowicz M., Dada F. T., Vallejo G. S., Manzur F., Isaza D., Molina D., Mesa J. G., Quintero A., Nyman K., Makela J., Strand J., Nieminen S., Taurio J., Kuusela M., Valle T., Pietila M., Kekki S., Strandberg T., Klutstein M., Greenberg G., Rozenman Y., Chorin E., Roguin A., Lewis B., Bashkin A., Tan E., Prado J. P., Ferrolino A., Babilonia N., Barbas B., Matiga G., Coching R. M., Drexel H., Brath H., Schnack C., Hanusch U., Fliesser-Gorzer E., Paulweber B., Ebenbichler C., Prager R., Huber K., Wolzt M., Auer J., Berger R., Schernthaner G. -H., Stanciulescu G., Creteanu M., Spiridon M., Dobreanu V., Vinereanu D., Iosipescu L. C., Istratoaie O., Coman I., Militaru C., Cinteza M., Sinnaeve P. R., Nicolau J. C., Kerr Saraiva J. F., Widimsky P., Kristensen S. D., Hartikainen J., Darius H., Tse H. F., Pais P., Lev E., de Luca L., Ramos Lopez G. A., Kontny F., Babilonia N. A., Zateyshchikov D. A., Ruda M., Elamin O., Kovar F., Dalby A. J., Bueno H., Chiang C. -E., Parkhomenko A., Nguyen T. Q., and Leonsson-Zachrisson M.
Abstract: Background: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. Methods: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). Findings: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3·3 years (IQR 2·8–3·8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7·3%] of 5558 vs 480 [8·6%] of 5596; HR 0·85 [95% CI 0·74–0·97], p=0·013). The same effect was not observed in patients without PCI (p=0·76, pinteraction=0·16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3·1%] with ticagrelor vs 183 (3·3%) with placebo
Published: 2019

5. Single large metastatic tumor growing progressively and occupying right ventricular cavity

Author: Yasuda, N, Ishiki, R, and Agetsuma, H
Published: 2002

6. Does stent fracture influence long-term outcomes?

Author: Umeda, H., primary, Okajima, T., additional, Suga, K., additional, Komoriya, Y., additional, Hayashi, K., additional, Miyake, H., additional, Ishiki, R., additional, Iwase, M., additional, and Murohara, T., additional
Published: 2013
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7. Nocturnal pulse-oxymetry can predict poor outcomes in patients with congestive heart failure a prospective study

Author: SUGINO, S, primary, ISHIKI, R, additional, OHTA, T, additional, YOKOTA, S, additional, MIYATA, S, additional, UMEDA, H, additional, TAKEICHI, Y, additional, IWASE, M, additional, INAGAKI, H, additional, and MUROHARA, T, additional
Published: 2008
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8. Safety and efficacy of 2.5-mm sirolimus-eluting stent implantation at lower deployment pressures in very small vessels (<2.5 mm).

Author: Umeda H, Iwase M, Gochi T, Izawa H, Ishiki R, Inagaki H, Shimizu T, Yokota M, Murohara T, Umeda, Hisashi, Iwase, Mitsunori, Gochi, Tomoko, Izawa, Hideo, Ishiki, Ryoji, Inagaki, Haruo, Shimizu, Takeshi, Yokota, Mitsuhiro, and Murohara, Toyoaki
Published: 2009
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9. Images in cardiology: Single large metastatic tumor growing progressively and occupying right ventricular cavity

Author: Yasuda, N., Ishiki, R., and Agetsuma, H.
Subjects: Heart, Cardiovascular tumors -- Diagnosis, Health, Diagnosis
Abstract: A 70 year old woman was admitted because of breathlessness and chest discomfort. An ovarian tumour had been resected six months before admission, and was diagnosed as a mature cystic [...]
Published: 2002

10. A new procedure to obtain Eu3+ doped oxide and oxosalt phosphors

Author: Serra, O. A., Cicillini, S. A., and Ishiki, R. R.
Published: 2000
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11. Empagliflozin in the treatment of heart failure with reduced ejection fraction in addition to background therapies and therapeutic combinations (EMPEROR-Reduced): a post-hoc analysis of a randomised, double-blind trial

Author: Subodh Verma, Nitish K Dhingra, Javed Butler, Stefan D Anker, Joao Pedro Ferreira, Gerasimos Filippatos, James L Januzzi, Carolyn S P Lam, Naveed Sattar, Barbara Peil, Matias Nordaby, Martina Brueckmann, Stuart J Pocock, Faiez Zannad, Milton Packer, M Packer, S Anker, J Butler, G Filippatos, S Pocock, F Zannad, JP Ferreira, M Brueckmann, J George, W Jamal, FK Welty, M Palmer, T Clayton, KG Parhofer, TR Pedersen, B Greenberg, MA Konstam, KR Lees, P Carson, W Doehner, A Miller, M Haas, S Pehrson, M Komajda, I Anand, J Teerlink, A Rabinstein, T Steiner, H Kamel, G Tsivgoulis, J Lewis, J Freston, N Kaplowitz, J Mann, J Petrie, S Perrone, S Nicholls, S Janssens, E Bocchi, N Giannetti, S Verma, J Zhang, J Spinar, M-F Seronde, M Boehm, B Merkely, V Chopra, M Senni, S Taddi, H Tsutsui, D-J Choi, E Chuquiure, HPB La Rocca, P Ponikowski, JRG Juanatey, I Squire, J Januzzi, I Pina, R Bernstein, A Cheung, J Green, S Kaul, C Lam, G Lip, N Marx, P McCullough, C Mehta, J Rosenstock, N Sattar, B Scirica, S Shah, C Wanner, D Aizenberg, L Cartasegna, F Colombo Berra, H Colombo, M Fernandez Moutin, J Glenny, C Alvarez Lorio, D Anauch, R Campos, A Facta, A Fernandez, R Ahuad Guerrero, L Lobo Márquez, RA Leon de la Fuente, M Mansilla, M Hominal, E Hasbani, M Najenson, G Moises Azize, H Luquez, L Guzman, H Sessa, M Amuchástegui, O Salomone, E Perna, D Piskorz, M Sicer, D Perez de Arenaza, C Zaidman, S Nani, C Poy, J Resk, R Villarreal, C Majul, T Smith Casabella, S Sassone, A Liberman, G Carnero, A Caccavo, M Berli, N Budassi, J Bono, A Alvarisqueta, J Amerena, K Kostner, A Hamilton, A Begg, J Beltrame, D Colquhoun, G Gordon, A Sverdlov, G Vaddadi, J Wong, J Coller, D Prior, A Friart, A Leone, G Vervoort, P Timmermans, P Troisfontaines, C Franssen, T Sarens, H Vandekerckhove, P Van De Borne, F Chenot, J De Sutter, E De Vuyst, P Debonnaire, M Dupont, O Pereira Dutra, LH Canani, MdC Vieira Moreira, W de Souza, LM Backes, L Maia, B De Souza Paolino, ER Manenti, W Saporito, F Villaça Guimarães Filho, T Franco Hirakawa, LA Saliba, FC Neuenschwander, CA de Freitas Zerbini, G Gonçalves, Y Gonçalves Mello, J Ascenção de Souza, L Beck da Silva Neto, EA Bocchi, J Da Silveira, JB de Moura Xavier Moraes Junior, JD de Souza Neto, M Hernandes, HC Finimundi, CR Sampaio, E Vasconcellos, FJ Neves Mancuso, MM Noya Rabelo, M Rodrigues Bacci, F Santos, M Vidotti, MV Simões, FL Gomes, C Vieira Nascimento, D Precoma, FA Helfenstein Fonseca, JA Ribas Fortes, PE Leães, D Campos de Albuquerque, JF Kerr Saraiva, S Rassi, FA Alves da Costa, G Reis, S Zieroth, D Dion, D Savard, R Bourgeois, C Constance, K Anderson, M-H Leblanc, D Yung, E Swiggum, L Pliamm, Y Pesant, B Tyrrell, T Huynh, J Spiegelman, J-P Lavoie, M Hartleib, R Bhargava, L Straatman, S Virani, A Costa-Vitali, L Hill, M Heffernan, Y Khaykin, J Ricci, M Senaratne, A Zhai, B Lubelsky, M Toma, L Yao, R McKelvie, L Noronha, M Babapulle, A Pandey, G Curnew, A Lavoie, J Berlingieri, S Kouz, E Lonn, R Chehayeb, Y Zheng, Y Sun, H 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Potu, R, Sai-Sudhakar, C, Saltzberg, M, Sauer, A, Shah, P, Skopicki, H, Bui, H, Carr, K, Stevens, G, Tahirkheli, N, Tallaj, J, Yousuf, K, Trichon, B, Welker, J, Tolerico, P, Vest, A, Vivo, R, Wang, X, Abadier, R, Dunlap, S, Weintraub, N, Malik, A, Kotha, P, Zaha, V, Kim, G, Uriel, N, Greene, T, Salacata, A, Arora, R, Gazmuri, R, Kobayashi, J, Iteld, B, Vijayakrishnan, R, Dab, R, Mirza, Z, Marques, V, Nallasivan, M, Bensimhon, D, Peart, B, Saint-Jacques, H, Barringhaus, K, Contreras, J, Gupta, A, Koneru, S, Nguyen, V, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: Male, medicine.medical_specialty, Angiotensin receptor, Glucoside, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Adrenergic beta-Antagonists, Angiotensin-Converting Enzyme Inhibitors, 030204 cardiovascular system & hematology, Placebo, 03 medical and health sciences, Angiotensin Receptor Antagonists, 0302 clinical medicine, Endocrinology, Mineralocorticoid receptor, Glucosides, Double-Blind Method, Internal medicine, Post-hoc analysis, Internal Medicine, medicine, Empagliflozin, Humans, 030212 general & internal medicine, Benzhydryl Compounds, ComputingMilieux_MISCELLANEOUS, Aged, Benzhydryl Compound, Heart Failure, Ejection fraction, business.industry, Angiotensin Receptor Antagonist, Adrenergic beta-Antagonist, Angiotensin-Converting Enzyme Inhibitor, Stroke Volume, medicine.disease, 3. Good health, Heart failure, ACE inhibitor, Female, Hypotension, business, medicine.drug, Human
Abstract: Contains fulltext : 249977.pdf (Publisher’s version ) (Closed access) BACKGROUND: It is important to evaluate whether a new treatment for heart failure with reduced ejection fraction (HFrEF) provides additive benefit to background foundational treatments. As such, we aimed to evaluate the efficacy and safety of empagliflozin in patients with HFrEF in addition to baseline treatment with specific doses and combinations of disease-modifying therapies. METHODS: We performed a post-hoc analysis of the EMPEROR-Reduced randomised, double-blind, parallel-group trial, which took place in 520 centres (hospitals and medical clinics) in 20 countries in Asia, Australia, Europe, North America, and South America. Patients with New York Heart Association (NYHA) classification II-IV with an ejection fraction of 40% or less were randomly assigned (1:1) to receive the addition of either oral empagliflozin 10 mg per day or placebo to background therapy. The primary composite outcome was cardiovascular death and heart failure hospitalisation; the secondary outcome was total heart failure hospital admissions. An extended composite outcome consisted of inpatient and outpatient HFrEF events was also evaluated. Outcomes were analysed according to background use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs) or angiotensin receptor neprilysin inhibitors (ARNIs), as well as β blockers and mineralocorticoid receptor antagonists (MRAs) at less than 50% or 50% or more of target doses and in various combinations. This study is registered with ClinicalTrials.gov, NCT03057977. FINDINGS: In this post-hoc analysis of 3730 patients (mean age 66·8 years [SD 11·0], 893 [23·9%] women; 1863 [49·9%] in the empagliflozin group, 1867 [50·1%] in the placebo group) assessed between March 6, 2017, and May 28, 2020, empagliflozin reduced the risk of the primary outcome (361 in 1863 participants in the empagliflozin group and 462 of 1867 in the placebo group; HR 0·75 [95% CI 0·65-0·86]) regardless of background therapy or its target doses for ACE inhibitors or ARBs at doses of less than 50% of the target dose (HR 0·85 [0·69-1·06]) and for doses of 50% or more of the target dose (HR 0·67 [0·52-0·88]; p(interaction)=0·18). A similar result was seen for β blockers at doses of less than 50% of the target dose (HR 0·66 [0·54-0·80]) and for doses of 50% or more of the target dose (HR 0·81 [0·66-1·00]; p(interaction)=0·15). Empagliflozin also reduced the risk of the primary outcome irrespective of background use of triple therapy with an ACE inhibitor, ARB, or ARNI plus β blocker plus MRA (given combination HR 0·73 [0·61-0·88]; not given combination HR 0·76 [0·62-0·94]; p(interaction)=0·77). Similar patterns of benefit were observed for the secondary and extended composite outcomes. Empagliflozin was well tolerated and rates of hypotension, symptomatic hypotension, and hyperkalaemia were similar across all subgroups. INTERPRETATION: Empagliflozin reduced serious heart failure outcomes across doses and combinations of disease-modifying therapies for HFrEF. Clinically, these data suggest that empagliflozin might be considered as a foundational therapy in patients with HFrEF regardless of their existing background therapy. FUNDING: Boehringer Ingelheim and Eli Lilly and Company.
Published: 2022
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12. Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI): a phase 3, placebo-controlled, randomised trial

Author: Deepak L Bhatt, Philippe Gabriel Steg, Shamir R Mehta, Lawrence A Leiter, Tabassome Simon, Kim Fox, Claes Held, Marielle Andersson, Anders Himmelmann, Wilhelm Ridderstråle, Jersey Chen, Yang Song, Rafael Diaz, Shinya Goto, Stefan K James, Kausik K Ray, Alexander N Parkhomenko, Mikhail N Kosiborod, Darren K McGuire, Robert A Harrington, Vladimir Santos, Ashit Jain, Irina Lendel, Michael Russo, W H Haught, Manuel Bouza, Harinder Gogia, Supratim Banerjee, George Kichura, Louis Kantaros, Francisco Padron, Rakesh Passi, Jay Stone, Michael Pursley, Michael D'Urso, Timothy Gardner, James Bennett, Khaled Nour, Satinder Saini, Wenwu Zhang, Dharam Kumbhani, Dustin Thomas, Dominick Angiolillo, Barry Bertolet, Amaury Roman-Miranda, Robert Black, Ramin Manshadi, Carlos Vaca, Antonio Blanco, Mark Napoli, David Brabham, Ayim Akyea-Djamson, Pratik Desai, Sudhir Prasada, Ajit Khaira, Leslie Forgosh, Ira Lieber, Guillermo Umpierrez, Dinesh Singal, Juan Londono, Neil Fraser, Jose Ruiz, Damaris Vega, Lilia Rodriguez, Christopher Brown, Faizullah Syed, Guarav Aggarwala, William Eaves, Michael Foster, Dinesh Gupta, David Avino, Wail Asfour, Glen Tonnessen, Xue-Qiao Zhao, Narendra Singh, Andrew Brockmyre, Norman Lepor, Nicolas Shammas, David Blick, Steven Hearne, John Prodafikas, Edgar Carell, Mark Izzo, Amin Karim, Bosh Zakhary, Mahmoud Atieh, Steven Leichter, Charles Meadows, David Hotchkiss, Mazen Abu-Fadel, Alan Wiseman, Jeffrey Bander, Mahesh Shah, Subhash Banerjee, Ricky Ganim, Karen Sopko, Misal Khan, Ramon Lloret, Troy Weirick, Rajendra Mehta, Udho Thadani, Anuj Bhargava, Mikhail Kosiborod, Jaynier Moya, Cezar Staniloae, Yamirka D Guerra, Anil Chhabra, Douglas Kosmicki, Wassim Shaheen, Akber Mohammed, J'Cinda Bitters, Jan Pattanayak, Julian Javier, Sunny Srivastava, Roland Phillips, Jessie Al-Amin, Michael Lillestol, Patrick Simpson, Lydie Hazan, Amit Amin, Gopi Shah, Denes Korpas, Bruce Platt, Jim Dickert, Orlando Puente, Louis Hiotis, Timothy Doyle, Raj Rajan, Alan Meholick, Christian Gring, Elie Hage-Korban, Robert Feldman, Harry Colfer, Samuel Butman, Malcolm Foster, Terence Hart, Randall Huling, Shervin Eshaghian, Ofsman Quintana, Deanna Cheung, Franklin Handel, Mara Rodriguez, David Suh, Paul Gordon, Gregg Pressman, Michael Bauer, William French, Mark Barettella, Sridhar Chatrathi, Damodhar Suresh, Ronald Goldberg, Mark Huth, Liwa Younis, Aref Rahman, Richard Mascolo, Michelle Welch, Randeep Suneja, Stephen Smith, Scott Shurmur, John Agaiby, Ahmad Jingo, Janice Johnston, Mary Beth, Anthony Vlastaris, Susan Kemp, Hamid Taheri, Edward Pereira, Michael Deyoung, Zafir Hawa, Ray Smith, Thomas Galski, Samer Garas, M Reddy, Susheel Sharma, Joeseph Hargrove, Charles Treasure, Ronald Emerson, Tariq Haddad, Kathryn Rohr, Larry Levinson, Raul Gaona, Barry Uretsky, Hiralal Maheshwari, Denny Lee, Stephanie Kinnaman, Robert Singal, Jeffrey Geohas, Osvaldo Gigliotti, Ajit Raisinghani, Charanjit Khurana, Brent Hella, Michael Kelberman, Steven Voyce, Sanjay Singh, Eric Lo, Pradeep Singh, Ross Goodfellow, Stuart Fischer, Richard Lorraine, Traci Turner, Jeffrey Shanes, Robert Busch, Robert Broker, Michelle Zaniewski, Kevin Pounds, Giselle Debs-Perez, Stephen Ong, Brad Frandsen, Douglas Fullington, Naseem Jaffrani, Ahtaram Khan, Marcus Lee, Joe Pouzar, George Revtyak, Julian Gonzalez, Samer Nakhle, Abel Murillo, Douglas Young, Sashi Makam, Mushtaq Syed, Kevin Woolf, Paul Grena, Sarab Alfata, Sharan Mahal, David Hoffman, Tinoy Kizhakekuttu, Joseph Deering, Janak Bhavsar, Scott Mikesell, William Wilson, Vance Wilson, Salah El, Francis Spinale, Vinod Kannarkat, Sunder Rao, Lenita Hanson, John Bertsch, Elena Gonzalez-Ortiz, Norma Severino, John Willis, Joel Schock, Ladan Bakhtari, Raul Gazmuri, Saadat Ansari, Jason Hall, Arvind Mehta, Neal Shealy, Stuart Zarich, Deovrat Singh, Kishor Vora, Nabil Andrawis, Darron Molter, David Maron, Jose Cardona, Ronald D'Agostino, Tamjeed Arshad, Rodney Samaan, David Jones, Dale Presser, John Heath, Sandy Green, George Bittar, Sheldon Henry, David Korn, John Schmedtje, Venkatesh Nadar, Bruce Graham, Ajay Labroo, Leonardo Clavijo, Hal Roseman, Gilbert Ledesma, Robert Rosen, Isaac Dor, William Kirby, Jennefer Sutton, Frank Eder, Bruce Iteld, Jose Gomez-Cortes, Maurice Buchbinder, Joseph Kasper, Antonio Terrelonge, Gustavo Torres, Ted Jagielo, Jose Alvarez, Yehuda Handelsman, Mario Guillen, Randall Richwine, Lorena Lewy-Alterbaum, Clinton Corder, Moogali Arvind, David Bolshoun, Magdy Mikhail, Stephen Minton, Odilon Alvarado, J Abbott, Brett Cauthen, Ryan Welter, Randy Mintz, John Cox, Annette Quick, Melvin Weiss, Johnny Dy, James Zebrack, Glenn Gandelman, Vinayak Hegde, Marc Silver, Michele DeGregorio, William Lawson, Christopher Paa, Anna Bortnick, Merrill Krolick, Rodolfo Sotolongo, Jorge Cheirif, Priya Kumar, Preetham Jetty, Ambar Patel, Mariusz Kruk, Iwona Kobielusz-Gembala, Barbara Rewerska, Adam Madrzejewski, Krzysztof Milewski, Jerzy Cygler, Joanna Petryka-Mazurkiewicz, Waldemar Jastrzebski, Janusz Korecki, Wojciech Fil, Janusz Prokopczuk, Anna Bochenek, Marek Wujkowski, Robert Witek, Piotr Konczakowski, Pawel Miekus, Marcin Szczasny, Wlodzimierz Musial, Krzysztof Cymerman, Jacek Lampart, Jacek Mikosinski, Slawomir Szynal, Issa Fares, Grzegorz Opolski, Stanislaw Mazur, Beata Wozakowska-Kaplon, Renata Bijata-Bronisz, Lukasz Wierucki, Beata Losa, Grzegorz Drelich, Marek Konieczny, Pawel Starczewski, Lidia Pawlowicz, Pawel Jesionowski, Jaroslaw Jurowiecki, Jacek Gniot, Mariusz Czyzycki, Karol Stania, Izabela Kucharczyk-Bauman, Benita Busz-Papiez, Agnieszka Karczmarczyk, Wanda Sudnik, Alina Koszek, Piotr Kolodziej, Bartosz Skwarna, Nicolás Jaramillo, Maciej Jankowski, Wojciech Czochra, Leszek Kinasz, Beata Miklaszewicz, Teresa Stasinska, Wladyslaw Pluta, Marcin Basiak, Teresa Rusicka, Izabela Niedbal-Yahfouf, Grazyna Popenda, Romuald Korzeniak, Agnieszka Mirek, Rafal Mariankowski, Lukasz Wojnowski, Marek Korol, Jacek Baszak, Piotr Podolec, Wojciech Piesiewicz, Aleksander Zurakowski, Carlos Luengas, Marek Skura, Piotr Pilecki, Piotr Majchrzak, Ewa Krzyzagórska, Marcin Drozd, Barbara Kaczmarek, Teresa Sliwinska, Katarzyna Zelazowska, Rafal Sztembis, Katarzyna Landa, Lidia Matyszczak-Toniak, Krzysztof Strojek, Marek Piepiorka, Robert Malinowski, Maria Górska, Edyta Stolarczyk-Sowa, Leszek Romanowski, Elzbieta Zinka, Zygfryd Reszka, Joanna Skierkowska, Anna Uzunow, Ewa Laskowska-Derlaga, Ekaterina Puntus, Elena D Kosmacheva, Natalia Koziolova, Prokhor Pavlov, Tatiana Supryadkina, Yury Didenko, Philipp Kopylov, Andrei Kazakov, Sergei Aksentiev, Elena Vishneva, Alexey Repin, Olga Smolenskaya, Olga Mantserova, Oleg Khrustalev, Elena Privalova, Vladimir Konstantinov, Svetlana Boldueva, Andrey Ezhov, Alexander Chernyavsky, Gadel Kamalov, Albert Galyavich, Galina Zubeeva, Galina Nechaeva, Sergey Shustov, Nino Dzhaiani, Tatiana Treshkur, Nataliya Osokina, Alexey Panov, Elena Shutemova, Valeriy Makukhin, Tatiana Kropotina, Larisa Tsyba, Yuri Karpov, J M Sizova, Marina Ballyuzek, Nikolay Tarasov, Elena Demchenko, Olga Barbarash, Valentin Moiseev, Valentin Markov, Vadim Kuznetsov, Inna Viktorova, Igor Sergienko, Lyudmila Ermoshkina, Niyaz Khasanov, Tatiana Khlevchuk, Andrey Baglikov, Sergey Shalaev, Elena Zonova, Elena Reznik, Larisa Haisheva, Tatyana Morugova, Nikita Lomakin, Alexander Vishnevsky, Yuri Shvarts, Olga Magnitskaya, Marina Mikhailusova, Elena Pavlysh, Igor Libov, Anna Zateyschikova, Victor Kostenko, Anton Edin, Yaroslava Khovaeva, Konstantin Zakharov, Raisa Stryuk, Vladimir Khirmanov, Sergey Kanorskiy, Sergey Yakushin, Anna Barabashkina, Hongwei Li, Qiang Zhao, Jian Zhang, Jianhua Ma, Yong He, Ming Luo, Aidong Zhang, Ningru Zhang, Yingru Chai, Genshan Ma, Hao Wang, Zhigang Liu, Lanjie He, Zhifang Song, Xiaolin Dong, Liang Tao, Zhanquan Li, Xi Su, Xiangqing Kong, Heping Niu, Junbo Ge, Zhurong Luo, Wenjun Huang, Daoquan Peng, Zuyi Yuan, Maria Milanova, Doncho Tenev, Antoni Gogov, Dimitar Karageorgiev, Todor Kolchev, Nikolay Rusev, Nikolina Georgieva, Rumen Kondov, Veselin Rusinov, Ivo Petrov, Georgi Stanchev, Mariana Konteva, Adriana Dincheva, Zdravka Yaneva, Ralitsa Vatova, Katya Ilieva, Nikolai Runev, Borislav Kolomanov, Ivan Petrov, Nikolay Iliev, Snezhanka Tisheva, Boryana Chompalova, Maria Tokmakova, Dimitar Raev, Kolyo Byanov, Dimitar Markov, Lenko Mihov, Atanas Mihov, Nora Milcheva, Milen Minchev, Mihail Mollov, Borislav Borisov, Tihomir Tihchev, Venelin Karakolev, Bojidar Dimov, Svetoslav Georgiev, Lachezar Smilov, Bon K Koo, Taehoon Ahn, Soon J Hong, Junghan Yoon, Seok K Oh, Myung H Jeong, Doo-Il Kim, Kiyuk Chang, Weon Kim, Joo-Yong Hahn, Kwang S Cha, Jung-Hee Lee, Si-Wan Choi, Chang-Wook Nam, In-Ho Chae, Yong H Park, Seung-Jea Tahk, Won-Yong Shin, Jei-Keon Chae, Byung J Kim, Jang-Whan Bae, Woo J Park, Seung W Rha, Young J Choi, Jin-Yong Hwang, Hun S Park, Luciano Baracioli, Fabio Guimaraes, Eduardo Vasconcellos, José Saraiva, Adamastor Pereira, Queulla Santos, Paulo Rossi, Lilia Maia, Miguel Madeira, Marcio Pereira, Roberto Botelho, Gilmar Reis, Freddy Eliaschewitz, Joao Borges, Carlos Nascimento, Jose A Fortes, Weimar de Souza, Pedro Pimentel, Miguel Hissa, Marcos Franchetti, Dalton Precoma, Costantino Ortiz, Mauro Hernandes, Wladmir Saporito, Fabio R dos Santos, Adrian Kormann, Fernando Neuenschwander, Oscar Dutra, Nelson Rassi, Luiz Tanajura, Juliana Souza, Delcio S Junior, Paulo Leaes, Adriana Forte, Teresa C Bonansea, Jose Marin, Bruno Machado, Maria J Cerqueira, Frederico Silva, Yorghos Michalaros, Euler Manenti, Cintia Cercato, Estevao Figueiredo, Ming-En Liu, Yi-Chih Wang, Tsung-Ming Lee, Chih Fang, Yen-Wen Wu, Kwo-Chang Ueng, Huey-Herng Sheu, Wen T Lai, I-Chang Hsieh, Zhih-Cherng Chen, Mu-Jang Lee, Chern Chiang, Kou-Gi Shyu, Chien-Hsun Hsia, Guang-Yuan Mar, Shih-Hung Chan, Chih-Cheng Wu, Wei-Kung Tseng, Kuan-Cheng Chang, Hung-I Yeh, Ji-Hung Wang, Charles Hou, Inna Sorokina, Maryna Dolzhenko, Olha Horoshko, Oleksandr Karpenko, Leonid Rudenko, Igor Vakaliuk, Anna 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Mansour, Saleem Kassam, Stephen Cheung, Anthony D Siega, Dennis O'Keefe, Eric Sabbah, Alan Bell, Guy Chouinard, Brian Wong, Mark Miller, Daniel Gaudet, Pierre Lachance, Iqbal Bata, Robert Petrella, Denis Gossard, Richard Dumas, Douglas Ing, Hagop Boyrazian, Ricardo Bessoudo, Thao T Huynh, Randy Hart, Jasmin Belle-Isle, Dinkar Shukla, Allan Kelly, Giuseppe Mazza, James Cha, Sam Henein, Andre Frechette, Saul Vizel, Joanne F Liutkus, Michael O'Mahony, Frank Halperin, Jacobus Kooy, John Graham, Allan Bailey, Ronald Wojcik, Igor Wilderman, Tibor Turi, Ákos Motyovszki, Béla Merkely, Csaba Király, Péter Andrássy, Zsolt Sárszegi, Tibor Fülöp, Zsolt Zilahi, István Édes, Andras Papp, Gábor Müller, Anna Czigány, Szilárd Zólyomi, László Korányi, János Takács, Ferenc Juhász, Bela Benczur, Sándor Kancz, András Földi, András C Nagy, Judit Bakai, István Greschik, László Püski, László Nagy, Róbert Kirschner, Roman Kuchar, Petr Hajek, Ladislav Busak, Daniel Michalik, Ivo Matyasek, Ivana Marusincova, 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Giovanni Amoroso, Gabriela Carnero, Ernesto Duronto, Diego Besada, Carolina Chacon, Pedro Zangroniz, Silvana Solis, Alberto Liberman, Virginia Sernia, Andres Alvarisqueta, Laura Maffei, Oscar G Vilamajo, Celso García, Maximiliano Sicer, Juan Muntaner, Anselmo Bordonava, Juan Albisu, Alejandra Zanini, Lucas Rista, Miguel Hominal, José N Estrada, Aldo Prado, Diego M Gosparini, Beatriz Schiavi, Armando G Castillo, José G Ruíz, Guillermo R Martinez, Víctor G López, Enrique L Rosas, Gabriel R Lopez, Elias G Cantu, Manuel de los Ríos Ibarra, Francisco P Padilla, Jose P Carrasco, Luis V Carrillo, Joel D García, Alfredo N Askar, Carlos A Salinas, Marco A Gamba, Carlos G Sanchez, Arnulfo G Cantú, Raul V Sánchez, Jaime C Madrigal, Rafael H Urbano, Andrés Í Romo, José R González Juanatey, Paolo Racugno, Angel C Fillat, José M de la Torre Hernández, Juan A Peláez, Jorge B Cortada, Pablo G Pavia, Manuel J Navarro, Roberto M Asenjo, Francisco F Díaz, Eduard B Peligero, Fernando A Manterola, Antonio F Ortiz, Juan D Mediavilla García, Francisco M Ortuño, Tomás R Vera, Alfonso S González, Jaime A Viñas, Francisco J Fernández Portales, Petra S Mayordomo, Francisco B Ojeda, Antonio R Domínguez, Rosa S González, Diego B Guerrero, Juan M Ruiz Nodar, Xavier G Marimon, José G Margáez, Roberto M Aguilera, José F Díaz Fernández, José L Zamorano Gómez, Vicente B González, Bruno G del Blanco, Ignacio P Pérez, Mercé R Moreno, Ainhoa R Ereño, José A García Lledó, Juan Prieto, Alex Villablanca, Carlos Raffo, Christian Pincetti, Carlos Conejeros, Oscar Roman, Manuel Rodriguez, Paola Varleta, Cindy Goldberg, Jorge Sandoval, German Arriagada, Lucio Leon, Sergio Potthoff, Jorge Cobos, Christian Figueroa, Ellen Makotoko, Nyda Fourie, Lesley Burgess, Hendrik Nortje, Rust Theron, Perumal Pillai, Naresh Ranjith, Julien Trokis, Soobramoney Pillay, Jeevren Reddy, Theema Nunkoo, Cornelia Kapp, Dorothea Urbach, Lawrence Distiller, Adrian Horak, Louis van Zyl, Kathleen Coetzee, Zelda Punt, Junaid Bayat, 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Hoffer, Geert Hollanders, Geert Vervoort, Patrick Coussement, Stefan de Maeseneire, Luc Janssens, Stein A Gravdal, Knut Risberg, Lars Gullestad, Ola D Hofseth, Dennis Nilsen, Knut T Lappegård, Christian van den Heuvel, Charlotte Gibbs, Alamdar Khusrawi, Satish Arora, Tadeusz Tomala, Thorbjørn Kjærnli, Jan Berg-Johansen, Robert Hagemeier, Gunnar Skjelvan, David Colquhoun, John Amerena, Claire Morbey, Christopher Hammett, Anthony Dart, Ronald Lehman, Andrew Hamilton, Matthew Worthley, Peter Purnell, Alan Whelan, Richard MacIsaac, Ktut Arya, Sultan Linjawi, Joseph Proietto, Lakshman Prasad, Aldo Rodriguez, Armando Godoy, Victor Rodriguez, Percy Berrospi, Carlos Chavez, Sandra Negron, Javier Heredia, Felix Medina, Helard Manrique, Walter Cabrera, Fernando Cordova, Trinidad Quinteros, Jaime M Haro, Susana Regalado, Javier Guitton, Hugo Arbanil, Michel Pansieri, Eric Decoulx, Pascal Goube, Axel de Labriolle, Jean N Labeque, Gregoire Range, Yves Cottin, Gilles Montalescot, Guillaume Cayla, Nicolas Danchin, Denis Angoulvant, Emile Ferrario, Meyer Elbaz, Olivier Dubreuil, Philippe G Steg, Caroline Fontaine, Emmanuel Sorbets, Hafiz Omer, Shukri Al-Saif, Hussam Al-Faleh, Abdullah Al-Shehri, Halia Alshehri, Rasha Bazari, Pak Hei, Man Ying, Michael Chan, Michelle Wong, Ronald Ma, Shing C Siu, Chiu C Tsang, Maurizio Ferrario, Emilio Assanelli, Michele Senni, Piermarco Piatti, Paolo Calabrò, Stefano Urbinati, Massimo Michisanti, Ferdinando Varbella, Salvatore de Cosmo, Roberto Trevisan, Sandro Bellotti, Giuseppe Di Pasquale, Angelo S Bongo, Massimo Uguccioni, Edoardo Mannucci, Ciro Mauro, Mauro Ragonese, Claudio Fresco, Maurizio Turturo, Rossella Marcucci, Manuel J Lievano Triana, Camilo Arana, Jose Accini, Rodrigo Botero, Marlena Muzyk-Osikowicz, Fredy T Dada, Gregorio S Vallejo, Fernando Manzur, Daniel Isaza, Dora Molina, Juan G Mesa, Alvaro Quintero, Kai Nyman, Jyrki Mäkelä, Jorma Strand, Sakari Nieminen, Jyrki Taurio, Matti Kuusela, Timo Valle, Mikko Pietilä, Sakari Kekki, 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Chern-En Chiang, Alexander Parkhomenko, Tuan Q Nguyen, Maria Leonsson-Zachrisson, Herrada, Anthony, Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Royal Brompton Hospital, McMaster University [Hamilton, Ontario], Keenan Research Centre of the Li Ka Shing Knowledge Institute [Toronto], St. Michael's Hospital, University of Toronto, Service de Pharmacologie médicale = service de pharmacologie - Dosage de médicaments [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Uppsala University Hospital, Uppsala Universitet [Uppsala], AstraZeneca, Tokai University, Uppsala University, Imperial College London, Saint Luke's Mid America Heart Institute, University of Missouri [Kansas City] (UMKC), University of Missouri System, University of New South Wales [Sydney] (UNSW), University of Texas Southwestern Medical Center [Dallas], Stanford University, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Université de Montpellier (UM), Bhatt, D, Steg, P, Mehta, S, Leiter, L, Simon, T, Fox, K, Held, C, Andersson, M, Himmelmann, A, Ridderstrale, W, Chen, J, Song, Y, Diaz, R, Goto, S, James, S, Ray, K, Parkhomenko, A, Kosiborod, M, Mcguire, D, Harrington, R, Santos, V, Jain, A, Lendel, I, Russo, M, Haught, W, Bouza, M, Gogia, H, Banerjee, S, Kichura, G, Kantaros, L, Padron, F, Passi, R, Stone, J, Pursley, M, D'Urso, M, Gardner, T, Bennett, J, Nour, K, Saini, S, Zhang, W, Kumbhani, D, Thomas, D, Angiolillo, D, Bertolet, B, Roman-Miranda, A, Black, R, Manshadi, R, Vaca, C, Blanco, A, Napoli, M, Brabham, D, Akyea-Djamson, A, Desai, P, Prasada, S, Khaira, A, Forgosh, L, Lieber, I, Umpierrez, G, Singal, D, Londono, J, Fraser, N, Ruiz, J, Vega, D, Rodriguez, L, Brown, C, Syed, F, Aggarwala, G, Eaves, W, Foster, M, Gupta, D, Avino, D, Asfour, W, Tonnessen, G, Zhao, X, Singh, N, Brockmyre, A, Lepor, N, Shammas, N, Blick, D, Hearne, S, Prodafikas, J, Carell, E, Izzo, M, Karim, A, Zakhary, B, Atieh, M, Leichter, S, Meadows, C, Hotchkiss, D, Abu-Fadel, M, Wiseman, A, Bander, J, Shah, M, Ganim, R, Sopko, K, Khan, M, Lloret, R, Weirick, T, Mehta, R, Thadani, U, Bhargava, A, Moya, J, Staniloae, C, Guerra, Y, Chhabra, A, Kosmicki, D, Shaheen, W, Mohammed, A, Bitters, J, Pattanayak, J, Javier, J, Srivastava, S, Phillips, R, Al-Amin, J, Lillestol, M, Simpson, P, Hazan, L, Amin, A, Shah, G, Korpas, D, Platt, B, Dickert, J, Puente, O, Hiotis, L, Doyle, T, Rajan, R, Meholick, A, Gring, C, Hage-Korban, E, Feldman, R, Colfer, H, Butman, S, Hart, T, Huling, R, Eshaghian, S, Quintana, O, Cheung, D, Handel, F, Rodriguez, M, Suh, D, Gordon, P, Pressman, G, Bauer, M, French, W, Barettella, M, Chatrathi, S, Suresh, D, Goldberg, R, Huth, M, Younis, L, Rahman, A, Mascolo, R, Welch, M, Suneja, R, Smith, S, Shurmur, S, Agaiby, J, Jingo, A, Johnston, J, Beth, M, Vlastaris, A, Kemp, S, Taheri, H, Pereira, E, Deyoung, M, Hawa, Z, Smith, R, Galski, T, Garas, S, Reddy, M, Sharma, S, Hargrove, J, Treasure, C, Emerson, R, Haddad, T, Rohr, K, Levinson, L, Gaona, R, Uretsky, B, Maheshwari, H, Lee, D, Kinnaman, S, Singal, R, Geohas, J, Gigliotti, O, Raisinghani, A, Khurana, C, Hella, B, Kelberman, M, Voyce, S, Singh, S, Lo, E, Singh, P, Goodfellow, R, Fischer, S, Lorraine, R, Turner, T, Shanes, J, Busch, R, Broker, R, Zaniewski, M, Pounds, K, Debs-Perez, G, Ong, S, Frandsen, B, Fullington, D, Jaffrani, N, Khan, A, 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Conejeros, C, Roman, O, Varleta, P, Goldberg, C, Sandoval, J, Arriagada, G, Corbalan, R, Leon, L, Potthoff, S, Cobos, J, Figueroa, C, Makotoko, E, Fourie, N, Burgess, L, Nortje, H, Theron, R, Pillai, P, Ranjith, N, Trokis, J, Pillay, S, Reddy, J, Nunkoo, T, Kapp, C, Urbach, D, Distiller, L, Horak, A, van Zyl, L, Coetzee, K, Punt, Z, Bayat, J, Dawood, S, Mitha, I, Padayachee, T, Hoosen, F, Dalby, A, Prabhavathi, Gowdaiah, P, Mehta, V, Chag, M, Gadkari, M, Ramamurthee, K, Das, A, Sawhney, J, Sathe, P, Adhyapak, S, Nguyen, T, Pham, V, Do, H, Nguyen, A, Nguyen, H, Truong, B, Jamil-Copley, S, Lang, C, Pell, A, Zaman, A, Storey, R, Swanson, N, Sharman, D, Braganza, D, Hammond, P, Moriarty, A, Bain, S, Pye, M, Sharp, A, Blagden, M, Randeva, H, Myhill, T, Viswanathan, G, Keeling, P, Clifford, P, Saxena, M, Lyons, K, Mcmurray, J, Jaafar, F, Murphy, C, Cartwright, S, Abouglila, K, Antalik, L, Krajci, P, Urban, M, Fazekas, F, Pella, D, Koleny, D, Vykoukalova, T, Macek, V, Vinanska, D, Jamriskova, L, Such, S, Fulop, P, Farsky, S, Bugan, V, Strbova, J, Micko, K, Palka Jr, J, Sivak, V, Kristensen, D, Refsgaard, J, Holmvang, L, Dixen, U, Nielsen, H, Egstrup, K, Jensen, L, Sykulski, R, Rasmussen, O, Andries, A, Luckow, A, Nielsen, G, Sorensen, T, Wongvipaporn, C, Chamnarnphol, N, Srimahachota, S, Sansanayudh, N, Kuanprasert, S, Tresukosol, D, Sookananchai, B, Kanadasi, M, Ozcan, T, Kucuk, M, Ongen, Z, Okuyan, E, Arat, A, Acikel, S, Yalcin, A, Guray, U, Ceyhan, C, Ozer, N, Arslan, S, Angeras, O, Johnston, N, Weiderman, A, Bandh, S, Hansen, O, Larnefeldt, H, Kusiak, D, Lindholm, C, Hedman, A, Erlinge, D, Curiac, D, Lundman, P, Zucconi-Mazzini, R, Aladellie, L, Jensen, J, Verwerft, J, Vrolix, M, Faes, D, Striekwold, H, Sinnaeve, P, Timmermans, P, Guedes, A, Delforge, M, Nimmegeers, J, Stammen, F, Buysschaert, I, Hoffer, E, Hollanders, G, Vervoort, G, Coussement, P, de Maeseneire, S, Janssens, L, Gravdal, S, Risberg, K, Gullestad, L, Hofseth, O, Nilsen, D, Lappegard, K, van den Heuvel, C, Gibbs, C, Khusrawi, A, Arora, S, Tomala, T, Kjaernli, T, Berg-Johansen, J, Hagemeier, R, Skjelvan, G, Colquhoun, D, Amerena, J, Morbey, C, Hammett, C, Dart, A, Lehman, R, Hamilton, A, Worthley, M, Purnell, P, Whelan, A, Macisaac, R, Arya, K, Linjawi, S, Proietto, J, Prasad, L, Rodriguez, A, Godoy, A, Rodriguez, V, Berrospi, P, Chavez, C, Negron, S, Heredia, J, Medina, F, Manrique, H, Cabrera, W, Cordova, F, Quinteros, T, Haro, J, Regalado, S, Guitton, J, Arbanil, H, Pansieri, M, Decoulx, E, Goube, P, de Labriolle, A, Labeque, J, Range, G, Cottin, Y, Montalescot, G, Cayla, G, Danchin, N, Angoulvant, D, Ferrario, E, Elbaz, M, Dubreuil, O, Fontaine, C, Sorbets, E, Omer, H, Al-Saif, S, Al-Faleh, H, Al-Shehri, A, El-Amin, O, Alshehri, H, Bazari, R, Hei, P, Ying, M, Chan, M, Wong, M, Ma, R, Siu, S, Tsang, C, Ferrario, M, Assanelli, E, Senni, M, Piatti, P, Calabro, P, Urbinati, S, Michisanti, M, Varbella, F, de Cosmo, S, Trevisan, R, Bellotti, S, Di Pasquale, G, Bongo, A, Uguccioni, M, Mannucci, E, Mauro, C, Ragonese, M, Fresco, C, Turturo, M, Marcucci, R, Lievano Triana, M, Arana, C, Accini, J, Botero, R, Muzyk-Osikowicz, M, Dada, F, Vallejo, G, Manzur, F, Isaza, D, Molina, D, Mesa, J, Quintero, A, Nyman, K, Makela, J, Strand, J, Nieminen, S, Taurio, J, Kuusela, M, Valle, T, Pietila, M, Kekki, S, Strandberg, T, Klutstein, M, Greenberg, G, Rozenman, Y, Chorin, E, Roguin, A, Lewis, B, Bashkin, A, Tan, E, Prado, J, Ferrolino, A, Babilonia, N, Barbas, B, Matiga, G, Coching, R, Drexel, H, Brath, H, Schnack, C, Hanusch, U, Fliesser-Gorzer, E, Paulweber, B, Ebenbichler, C, Prager, R, Huber, K, Wolzt, M, Auer, J, Berger, R, Schernthaner, G, Stanciulescu, G, Creteanu, M, Spiridon, M, Dobreanu, V, Vinereanu, D, Iosipescu, L, Istratoaie, O, Coman, I, Militaru, C, Cinteza, M, Nicolau, J, Kerr Saraiva, J, Widimsky, P, Kristensen, S, Hartikainen, J, Darius, H, Tse, H, Pais, P, Lev, E, de Luca, L, Ramos Lopez, G, Kontny, F, Zateyshchikov, D, Ruda, M, Elamin, O, Kovar, F, Bueno, H, Leonsson-Zachrisson, M, Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pharmacologie - Dosage de médicaments [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Royal Brompton and Harefield NHS Foundation Trust-Imperial College London
Subjects: Male, Platelet Aggregation Inhibitors/therapeutic use, THEMIS Steering Committee and Investigators, medicine.medical_treatment, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], 030204 cardiovascular system & hematology, Coronary Angiography, Stroke/epidemiology, Coronary artery disease, DOUBLE-BLIND, 0302 clinical medicine, Hemorrhage/chemically induced, acetylsalicylic acid, antidiabetic agent, placebo, ticagrelor, Secondary Prevention, Medicine, 030212 general & internal medicine, Myocardial infarction, Coronary Artery Bypass, Cardiovascular Diseases/mortality, 11 Medical and Health Sciences, OUTCOMES, Aspirin, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, General Medicine, Middle Aged, Clopidogrel, 3. Good health, Ticagrelor/therapeutic use, DRUG-ELUTING STENTS, CLOPIDOGREL, Cardiology, PLATELET INHIBITION, Drug Therapy, Combination, Female, Life Sciences & Biomedicine, Ticagrelor, TIMI, medicine.drug, Coronary Artery Disease/complications, medicine.medical_specialty, Hypoglycemic Agents/therapeutic use, POOLED ANALYSIS, 03 medical and health sciences, Medicine, General & Internal, Percutaneous Coronary Intervention, Double-Blind Method, General & Internal Medicine, Internal medicine, Myocardial Infarction/epidemiology, Humans, Aged, Science & Technology, ANTIPLATELET THERAPY, business.industry, Diabetes Mellitus, Type 2/complications, ELEVATION MYOCARDIAL-INFARCTION, RIVAROXABAN, Percutaneous coronary intervention, medicine.disease, ASPIRIN, Coronary Stenosis/diagnostic imaging, Aspirin/therapeutic use, Conventional PCI, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Contains fulltext : 215333.pdf (Publisher’s version ) (Closed access) BACKGROUND: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. METHODS: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). FINDINGS: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3.3 years (IQR 2.8-3.8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7.3%] of 5558 vs 480 [8.6%] of 5596; HR 0.85 [95% CI 0.74-0.97], p=0.013). The same effect was not observed in patients without PCI (p=0.76, pinteraction=0.16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3.1%] with ticagrelor vs 183 (3.3%) with placebo; HR 0.96 [95% CI 0.78-1.18], p=0.68), as well as all-cause death (282 [5.1%] vs 323 [5.8%]; 0.88 [0.75-1.03], p=0.11). TIMI major bleeding occurred in 111 (2.0%) of 5536 patients receiving ticagrelor and 62 (1.1%) of 5564 patients receiving placebo (HR 2.03 [95% CI 1.48-2.76], p
Published: 2019
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13. Sitagliptin on carotid intima-media thickness in type 2 diabetes patients receiving primary or secondary prevention of cardiovascular disease: A subgroup analysis of the PROLOGUE study.

Author: Tanaka A, Yoshida H, Nanasato M, Oyama JI, Ishizu T, Ajioka M, Ishiki R, Saito M, Shibata Y, Kaku K, Maemura K, Higashi Y, Inoue T, Murohara T, and Node K
Subjects: Aged, Aged, 80 and over, Cardiovascular Diseases diagnostic imaging, Cardiovascular Diseases epidemiology, Diabetes Mellitus, Type 2 diagnostic imaging, Diabetes Mellitus, Type 2 epidemiology, Dipeptidyl-Peptidase IV Inhibitors therapeutic use, Female, Humans, Male, Middle Aged, Prospective Studies, Single-Blind Method, Cardiovascular Diseases prevention & control, Carotid Intima-Media Thickness, Diabetes Mellitus, Type 2 drug therapy, Primary Prevention methods, Secondary Prevention methods, Sitagliptin Phosphate therapeutic use
Abstract: Background: Whether a dipeptidyl peptidase-4 (DPP-4) inhibitor can attenuate atherosclerosis is still controversial. Some clinical trials reported that DPP-4 inhibitors in diabetes patients without a previous history of cardiovascular (CV) events could reduce carotid intima-media thickness (IMT). However, in the PROLOGUE study, which enrolled diabetes patients both with and without previous CV events, sitagliptin failed to slow the progression of carotid IMT relative to conventional therapy., Aim and Methods: We hypothesized that the effect of DPP-4 inhibitors on carotid atherosclerosis might be different between the primary and secondary prevention groups. We performed a post hoc analysis of the PROLOGUE study and compared the effects of sitagliptin and conventional therapy on changes in carotid IMT in subgroups with or without previous CV events., Results: No significant difference in the IMT changes between the treatment groups was found in the secondary prevention subgroup (sitagliptin, N = 102; conventional, 111). However, in the primary prevention subgroup (sitagliptin, 120; conventional, 109), we found significant inhibitory effects of sitagliptin on mean and max internal carotid artery IMT [estimated group difference: -0.096 mm (95% CI -0.175 to -0.018, p = 0.017) and -0.162 mm (95% CI -0.272 to -0.052, p = 0.004), respectively], although there was no significant difference in the common carotid artery IMT., Conclusions: Our data suggest that there is a favorable effect of DPP-4 inhibitor treatment on carotid atherosclerosis in diabetes patients without previous CV events., (Copyright © 2018 Elsevier B.V. All rights reserved.)
Published: 2018
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14. [Coronary Artery Bypass Grafting for In-stent Restenosis Probably Caused by Allergic Response;Report of a Case].

Author: Eda T, Teshima Y, Suga K, Hayashi K, Miyake Y, Umeda H, and Ishiki R
Subjects: Coronary Restenosis immunology, Device Removal, Eosinophils immunology, Eosinophils pathology, Female, Humans, Hypersensitivity immunology, Macrophages immunology, Macrophages pathology, Middle Aged, Treatment Failure, Treatment Outcome, Cobalt adverse effects, Cobalt immunology, Coronary Artery Bypass, Off-Pump, Coronary Restenosis etiology, Coronary Restenosis therapy, Drug-Eluting Stents adverse effects, Hypersensitivity etiology, Myocardial Infarction therapy, Nickel adverse effects, Nickel immunology
Abstract: A 58-year-old female presented to our hospital with recurrence of chest pain. She had undergone coronary intervention using biolimus-eluting-stent for total occlusion of the left anterior descending artery(LAD) 3 years before. Since then in-stent restenosis had repeated 4 times in 3 years. In the interim, another everolimus-eluting-stent had been placed on the same lesion. The contact metal allergic patch test revealed the existence of allergic response to nickel and cobalt which were the structural components of these stents. She underwent off-pump coronary artery bypass grafting, and these stents were removed. The invasions of macrophages and eosinophils around the stent-s were pathologically proven. One year after surgery she is doing well without angina or allergic symptom. These observations suggested the allergic reaction of the coronary artery against the stents.
Published: 2016

15. High HDL cholesterol level after treatment with pitavastatin is an important factor for regression in carotid intima-media thickness.

Author: Okumura K, Tsukamoto H, Tsuboi H, Hirayama H, Kamiya H, Watarai M, Ishiki R, and Murohara T
Subjects: Aged, Biomarkers blood, Carotid Artery Diseases blood, Carotid Artery Diseases diagnostic imaging, Carotid Artery, Common diagnostic imaging, Comorbidity, Coronary Disease blood, Coronary Disease diagnostic imaging, Female, Humans, Japan, Male, Middle Aged, Predictive Value of Tests, Prospective Studies, Risk Factors, Time Factors, Treatment Outcome, Carotid Artery Diseases drug therapy, Carotid Artery, Common drug effects, Carotid Intima-Media Thickness, Cholesterol, HDL blood, Coronary Disease drug therapy, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Plaque, Atherosclerotic, Quinolines therapeutic use
Abstract: This study is a prospective multicenter study designed to investigate the effects of lipid-lowering therapy with pitavastatin on atherosclerotic plaque in patients with coronary heart disease, and to determine which factor is more closely associated with plaque regression. Participants (n = 63) were treated with pitavastatin for 12 months, and the carotid intima-media thickness (IMT) was measured by ultrasound before and after treatment. Mean IMT slightly but significantly decreased (from 0.99 ± 0.33 to 0.94 ± 0.28 mm for overall, P = 0.01) regardless of the presence of pretreatment with other statins. There were no significant relations with hs-CRP, malondialdehyde-LDL, LDL cholesterol, and smaller LDL cholesterol levels despite their decrease by pitavastatin. Decreases in mean IMT were observed significantly more frequently in subjects with high on-treatment HDL cholesterol levels than with low HDL cholesterol levels (P = 0.017). The change in mean IMT tended to be inversely correlated with increments in HDL cholesterol and apolipoprotein A-I. The IMT regression was more often observed in the absence of diabetes and metabolic syndrome. In conclusion, we demonstrated that treatment with pitavastatin attenuated atherosclerotic plaque. This effect was associated with the level of HDL cholesterol, and was stronger in the absence of diabetes and metabolic syndrome in our ischemic heart disease patients.
Published: 2015
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16. Impact of sirolimus-eluting stent fracture on 4-year clinical outcomes.

Author: Umeda H, Kawai T, Misumida N, Ota T, Hayashi K, Iwase M, Izawa H, Sugino S, Shimizu T, Takeichi Y, Ishiki R, Inagaki H, Ozaki Y, and Murohara T
Subjects: Aged, Drug-Eluting Stents statistics & numerical data, Female, Follow-Up Studies, Humans, Incidence, Male, Middle Aged, Risk Factors, Sirolimus administration & dosage, Treatment Outcome, Blood Vessel Prosthesis Implantation, Coronary Restenosis epidemiology, Coronary Restenosis etiology, Postoperative Complications, Prosthesis Failure adverse effects
Abstract: Background: Although stent fracture (SF) after sirolimus-eluting stent (SES) implantation has been recognized as one of the predisposing factors of in-stent restenosis, it remains uncertain whether SF can increase the risk of major adverse cardiac events (MACE), especially beyond 1 year after SES implantation. The aim of this study was to assess the impact of SF relative to non-SF on 4-year clinical outcomes after treatment with SES of comparable unselected lesions., Methods and Results: A total of 874 lesions in 793 patients undergoing SES implantation and subsequent angiography 6 to 9 months after index procedure were analyzed. At 6- to 9-month angiographic follow-up, SF was identified in 70 of 874 lesions (8.0%). In-stent late loss was significantly higher in SF lesions versus non-SF lesions (0.42±0.59 mm versus 0.13±0.49 mm, P<0.001), resulting in a significantly higher in-stent restenosis rate (21.4% versus 4.1%, P<0.001). At 4 years, SF versus non-SF was associated with a significantly higher MACE rate (23.2% versus 12.6%, P=0.014), mainly driven by significantly higher target-lesion revascularization (18.8% versus 10.2%, P=0.029) rate. Adverse effects of SF on clinical outcomes occurred mostly within the first year (17.4% versus 6.6%, P=0.001), with similar MACE rate between 1 and 4 years (5.8% versus 5.9%, P=0.611). No significant differences between SF versus non-SF patients were observed in the cumulative frequency of very late stent thrombosis (2.9% versus 1.4%, P=0.281), death (0% versus 2.1%, P=0.252), or myocardial infarction (5.8% versus 2.9%, P=0.165)., Conclusions: SF of SES was associated with higher MACE rate up to 1 year, mainly driven by higher target-lesion revascularization, whereas no significant association was evident between years 1 and 4.
Published: 2011
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17. Subtle myocardial damage associated with diagnostic coronary angiography alone.

Author: Umeda H, Ota T, Iwase M, Izawa H, Miyata S, Sugino S, Hayashi K, Misumida N, Takeichi Y, Ishiki R, Inagaki H, and Murohara T
Subjects: Biomarkers blood, Coronary Disease blood, Female, Follow-Up Studies, Humans, Male, Prognosis, Retrospective Studies, Risk Factors, Coronary Angiography adverse effects, Coronary Disease diagnostic imaging, Creatine Kinase blood, Myocardium metabolism, Troponin I blood
Abstract: Aims: To evaluate the frequency, predictors and prognostic significance of elevation in cardiac troponin I (cTnI) after coronary angiography (CAG)., Methods and Results: A series of 296 consecutive patients with normal pre-procedural cTnI levels and undergoing elective CAG at our centre were prospectively analysed. Positive cTnI elevation was defined as >0.06 ng/ml. Positive cTnI elevation was observed in 44 patients (14.8%), but CK-MB was elevated in only four patients (1.3%) after the procedure. The risk of cTnI elevation was independently associated with left ventricular hypertrophy (odds ratio [OR] 5.52; 95% confidence interval [CI], 2.54 to 12.02; P<0.001), inexperienced operator (OR 10.83; 95% CI, 2.47 to 47.43; P=0.002) and the amount of contrast agent (OR 1.12; 95% CI, 1.03 to 1.23; P=0.009 for each 10 ml increase), whereas it was not associated with the severity of coronary artery disease. At one year, however, postprocedural elevation of cTnI was not associated with an increased risk of death (2.3% vs. 0.8%, P=0.384) or myocardial infarction (2.3% vs. 2.0%, P=0.623)., Conclusions: A minor elevation of cTnI is observed commonly after CAG, which might be associated with left ventricular hypertrophy, operator's experience and the amount of contrast used; however, it does not influence 1-year events rates.
Published: 2010
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18. Relationship between severity of renal impairment and 2-year outcomes after sirolimus-eluting stent implantation.

Author: Ota T, Umeda H, Yokota S, Miyata S, Takamura A, Sugino S, Hayashi K, Ishiki R, Takeichi Y, Iwase M, Inagaki H, and Murohara T
Subjects: Aged, Cause of Death, Comorbidity, Coronary Angiography, Coronary Restenosis mortality, Disease-Free Survival, Equipment Failure Analysis, Female, Follow-Up Studies, Glomerular Filtration Rate physiology, Humans, Kaplan-Meier Estimate, Kidney Failure, Chronic diagnosis, Kidney Failure, Chronic mortality, Kidney Failure, Chronic therapy, Male, Middle Aged, Multivariate Analysis, Myocardial Infarction diagnosis, Myocardial Infarction mortality, Proportional Hazards Models, Renal Dialysis, Risk Factors, Angioplasty, Balloon, Coronary, Coronary Restenosis etiology, Drug-Eluting Stents, Kidney Failure, Chronic complications, Myocardial Infarction therapy, Sirolimus administration & dosage
Abstract: Background: The presence of chronic kidney disease (CKD) is associated with an increased risk of restenosis and major adverse cardiac events (MACEs) after coronary interventions, especially in patients on hemodialysis (HD). The aim of this study was to assess the impact of varying degrees of renal impairment on angiographic and 2-year clinical outcomes after treatment with sirolimus-eluting stents (SESs)., Methods: A total of 675 lesions of 593 patients treated with SES were analyzed. Patients were classified into 3 groups: 34 patients on HD; 337 patients with estimated glomerular filtration rate > or =60 mL min(-1) 1.73 m(-2) (non-CKD group); and 222 patients who had lower estimated glomerular filtration rate <60 mL min(-1) 1.73 m(-2) without HD dependency (CKD group)., Results: At angiographic follow-up (201 +/- 73 days), in-segment late loss was markedly higher in the HD group versus the non-CKD and CKD groups (0.68 +/- 1.06 vs 0.11 +/- 0.45 and 0.15 +/- 0.50 mm, respectively, P < .001), resulting in a significantly higher in-segment restenosis rate (40.0% vs 10.4% and 11.5%, respectively, P < .001). At 2 years, HD vs non-CKD and CKD was associated with a significantly higher MACE rate (35.3% vs 10.4% and 12.6%, respectively, P < .001), mainly driven by significantly higher mortality (11.8% vs 0.6% and 2.3%, respectively, P < .001) and target-lesion revascularization (23.5% vs 9.2% and 8.1%, respectively, P = .016) rates. Multivariable analysis revealed that HD was the independent predictor of 2-year MACE (hazard ratio 4.70, 95% CI 2.40-9.20, P < .001)., Conclusions: Although angiographic and clinical outcomes after SES implantation were similarly favorable in non-HD-dependent CKD patients, regardless of renal function, in patients with end-stage CKD requiring HD, frequencies of restenosis and 2-year MACE were markedly higher than in non-HD-dependent patients.
Published: 2009
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19. Frequency, predictors and outcome of stent fracture after sirolimus-eluting stent implantation.

Author: Umeda H, Gochi T, Iwase M, Izawa H, Shimizu T, Ishiki R, Inagaki H, Toyama J, Yokota M, and Murohara T
Subjects: Coronary Restenosis etiology, Coronary Restenosis pathology, Female, Follow-Up Studies, Forecasting, Humans, Male, Prospective Studies, Prosthesis Implantation instrumentation, Time Factors, Treatment Outcome, Coronary Restenosis epidemiology, Drug-Eluting Stents adverse effects, Prosthesis Failure, Prosthesis Implantation adverse effects, Prosthesis Implantation trends, Sirolimus administration & dosage
Abstract: Background: Recently, stent fracture (SF) of sirolimus-eluting stents (SES) has been shown to be associated with an increased risk of in-stent restenosis. We sought to evaluate the incidence, predictors and clinical outcome of SF after SES implantation in comparable unselected lesions., Methods: A total of 430 lesions of 382 patients treated with SES were analyzed. SF was defined as single or multiple stent strut fracture as well as complete separation of stent segments., Results: At follow-up, SF was identified in 33 of 430 lesions (7.7%). In lesions with SF, the in-stent restenosis was observed more frequently than non-SF lesions (15.2% vs. 4.0%, P=0.004). At 450 days, however, the cumulative rate of major cardiac events was not significantly different between lesions with and without SF (9.1% vs. 7.1%, P=0.722). The risk of SF was independently associated with total stent length (OR 2.22; 95% CI, 1.25 to 3.95; P=0.007), the change in the angulation of the lesion after stenting (OR 1.55; 95% CI, 1.07 to 2.25; P=0.020), and the right coronary artery lesions (OR 3.26; 95% CI, 1.18 to 8.96; P=0.022)., Conclusions: The occurrence of SF after SES implantation, was found to be relatively common in the particular population, however, did not lead to an increased risk of adverse cardiac events at 450 days, despite a higher incidence of in-stent restenosis.
Published: 2009
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20. Is it possible to predict which patients need distal protection during primary angioplasty?

Author: Umeda H, Iwase M, Izawa H, Katoh T, Gochi T, Toyama J, Yokoya M, Matsushita T, Ishiki R, Inagaki H, Murohara T, and Yokota M
Subjects: Aged, Chi-Square Distribution, Coronary Angiography, Coronary Circulation physiology, Electrocardiography, Female, Humans, Male, Microcirculation, Myocardial Infarction diagnostic imaging, Predictive Value of Tests, Statistics, Nonparametric, Thrombosis etiology, Tomography, Emission-Computed, Single-Photon, Treatment Outcome, Angioplasty, Balloon, Coronary, Balloon Occlusion instrumentation, Myocardial Infarction physiopathology, Myocardial Infarction therapy, Thrombosis prevention & control
Abstract: Background: Although the benefit of distal protection (DP) during primary percutaneous coronary intervention (PCI) remains questionable, there appears to be efficacy in some clinical situations. We sought to identify in patients with ST-segment elevation acute myocardial infarction (STEMI) which clinical and angiographic characteristics might indicate the patient who will benefit from the use of a DP device., Methods: A series of 103 consecutive patients with STEMI undergoing primary PCI using DP were compared with 98 consecutive patients treated by primary PCI alone., Results: The overall rates of thromboembolic complications and achievement of optimal reperfusion (myocardial blush grade >/=2 and ST-segment resolution >/=70%), and infarct size, were similar between the 2 groups. However, DP use was associated with higher rates of optimal reperfusion in patients with right coronary artery (RCA) lesions (OR 2.45; 95% CI, 1.07 to 5.59; P=0.034), thrombus score >/=4 (OR 2.64; 95% CI, 1.07 to 6.50; P=0.034) or infarct-related artery (IRA) of >/=3.5 mm in diameter (OR 4.09; 95% CI, 1.02 to 16.40; P=0.047). In this population (RCA location, thrombus score >/=4, or IRA >/=3.5 mm), DP use reduced the risk of thromboembolic complications (64%, P=0.012, 45%, P=0.035 and 54%, P=0.050, respectively), resulting in a smaller infarct size (8.0+/-5.1 vs. 11.7+/-7.5, P=0.028, 13.1+/-8.8 vs. 17.4+/-10.0, P=0.026 and 15.5+/-10.8 vs. 22.1+/-10.1, P=0.042, respectively)., Conclusions: The use of a DP during primary PCI may lead to a reduction of thromboembolic complications, subsequent higher rates of optimal reperfusion and reduced infarct size in patients with RCA culprit lesions, a large thrombus, or large IRA.
Published: 2008
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21. Diversity of the elevation of serum cardiac troponin I levels in patients during their first visit to the emergency room.

Author: Saiki A, Iwase M, Takeichi Y, Umeda H, Ishiki R, Inagaki H, Kato Y, Nagata K, and Koike Y
Subjects: Acute Coronary Syndrome diagnosis, Acute Coronary Syndrome pathology, Adolescent, Adult, Aged, Aged, 80 and over, Cardiomyopathies blood, Cardiomyopathies diagnosis, Cardiomyopathies pathology, Creatine Kinase blood, Female, Heart Failure blood, Heart Failure diagnosis, Heart Failure pathology, Humans, Male, Middle Aged, Myocarditis blood, Myocarditis diagnosis, Myocarditis pathology, Myocardium pathology, Myoglobin blood, Predictive Value of Tests, Pulmonary Embolism blood, Pulmonary Embolism diagnosis, Pulmonary Embolism pathology, Renal Insufficiency blood, Renal Insufficiency diagnosis, Renal Insufficiency pathology, Retrospective Studies, Tachycardia blood, Tachycardia diagnosis, Tachycardia pathology, Acute Coronary Syndrome blood, Emergency Service, Hospital, Myocardium metabolism, Troponin I blood
Abstract: Background: Although measurement of serum creatine kinase levels, as well as myoglobin levels, has been used for screening patients with acute coronary syndrome (ACS), the specificity of both is low. Measurement of cardiac troponin levels is now extensively used for the diagnosis of ACS because of their superior cardiac specificity. However, troponin levels are reportedly elevated not only in patients with ACS but also in those with other diseases., Methods and Results: The clinical characteristics of 1,023 patients (mean age: 63.5+/-16.3 years; males: 665, females: 358) whose serum cardiac troponin I (cTnI) levels had been measured at the initial visit to the emergency room of Toyota Memorial Hospital between April 2004 and March 2005 were retrospectively analyzed. A positive elevation of cTnI was defined as cTnI > or =0.03 ng/ml. There were 432 patients (42.2%) with positive cTnI levels. The cTnI levels (8.48+/-2.64 ng/ml) in patients with acute myocardial infarction (AMI) were greater than those (0.25+/-0.07 ng/ml) in patients with unstable angina pectoris (AP), as well as those (0.04+/-0.01 ng/ml) in patients with stable AP. In terms of the diagnosis of AMI, the sensitivity was high enough (94.6%), but its specificity was relatively low (61.9%). Furthermore, the differentiation between AMI and unstable AP by the cTnI value alone was impossible. The cTnI levels were elevated in patients with a variety of diseases other than ACS, including heart failure, cardiomyopathies, myocarditis, renal failure, tachyarrhythmias, and pulmonary embolism., Conclusions: Elevation of the cTnI level is frequently observed in patients in the emergency room with common diseases other than ACS.
Published: 2007
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22. Photocatalytic degradation of imazethapyr herbicide at TiO2/H2O interface.

Author: Rumi Ishiki R, Mitsugu Ishiki H, and Takashima K
Subjects: Catalysis, Chromatography, High Pressure Liquid, Hydrogen Peroxide analysis, Hydrogen-Ion Concentration, Kinetics, Models, Chemical, Photochemistry, Photolysis, Quaternary Ammonium Compounds analysis, Spectrophotometry, Temperature, Herbicides chemistry, Light, Nicotinic Acids chemistry, Titanium chemistry, Water chemistry
Abstract: The photocatalytic degradation of imazethapyr, a herbicide of the imidazolinone family, was investigated in an aqueous suspension of titanium dioxide used as a catalyst. A pseudo-first order kinetic model was employed to discuss the results. The effect of catalyst loading, initial concentration of imazethapyr, hydrogen peroxide, pH value, and temperature were investigated. Imazethapyr disappearance as a function of irradiation time was analyzed by HPLC. The ammonium ion formation was determined spectrophotometrically at 694 nm. The degradation was observed to proceed more favorably at natural pH (ca. 4.4) when the pH was varied in the range from 2 to 11. The addition of hydrogen peroxide to the TiO2 suspension enhanced the degradation rate constant up to 5.0x10(-3) mol l-1, but decreased it at higher concentrations. The degradation rate constants decreased by 19% with a temperature increase from 20 to 40 degrees C in the TiO2 suspension, whereas a 16% increase in imazethapyr direct photolysis was observed for the same temperature range. This behavior indicates the occurrence of physisorption between TiO2 and imazethapyr molecules.
Published: 2005
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23. Promising efficacy of primary gradual and prolonged balloon angioplasty in small coronary arteries: a randomized comparison with cutting balloon angioplasty and conventional balloon angioplasty.

Author: Umeda H, Iwase M, Kanda H, Izawa H, Nagata K, Ishiki R, Sawada K, Murohara T, and Yokota M
Subjects: Aged, Analysis of Variance, Angioplasty, Balloon adverse effects, Angioplasty, Balloon instrumentation, Angioplasty, Balloon, Coronary adverse effects, Atherectomy, Coronary methods, Coronary Angiography, Coronary Restenosis prevention & control, Coronary Stenosis diagnostic imaging, Coronary Stenosis pathology, Cross-Over Studies, Equipment Design, Female, Humans, Male, Middle Aged, Statistics, Nonparametric, Stents, Treatment Outcome, Angioplasty, Balloon methods, Coronary Stenosis therapy, Coronary Vessels pathology
Abstract: Background: Small vessel size represents a critical risk factor for an adverse outcome after both conventional balloon angioplasty (POBA) and stenting. Gradual and prolonged balloon angioplasty (GPBA) has been shown to cause less arterial trauma, which results in higher procedural success rates and fewer in-hospital complications than POBA. The aim of this study was to assess the clinical and angiographic benefits of primary GPBA with a perfusion balloon in small coronary arteries, as compared with cutting balloon angioplasty (CBA) and POBA., Methods: A total of 263 patients with symptoms and reference diameters <3.0 mm were randomly assigned to undergo GPBA (n = 85), CBA (n = 88), or POBA (n = 90). The cumulative inflation time must be >10 minutes in GPBA. Crossover to stent was allowed for inadequate results. Follow-up angiography was performed after 6 months. The primary end point was angiographic restenosis at follow-up., Results: Compared with POBA, GPBA resulted in a lower final residual diameter stenosis (27.3% vs 34.2%, P =.01) and decreased the need for stent placement (8.0% vs 22.2%, P =.031). At follow-up, the restenosis rates were lower with GPBA (31.3%, P =.034) and CBA (32.9%, P =.059) than POBA (50.6%). Target lesion revascularization was less frequently needed with GPBA (20.5%, P =.043) and CBA (20.0%, P =.033) than POBA (37.6%). Additionally, the event-free survival rate was higher with GPBA (77.1%, P =.033) and CBA (76.4%, P =.047) than POBA (58.8%)., Conclusions: In small coronary arteries, both GPBA and CBA resulted in favorable angiographic and clinical outcomes. With a lower restenosis rate and target lesion revascularization rate, GPBA may be a superior strategy for small vessels compared with POBA.
Published: 2004
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24. Growth hormone-releasing peptide can improve left ventricular dysfunction and attenuate dilation in dilated cardiomyopathic hamsters.

Author: Iwase M, Kanazawa H, Kato Y, Nishizawa T, Somura F, Ishiki R, Nagata K, Hashimoto K, Takagi K, Izawa H, and Yokota M
Subjects: Animals, Atrial Natriuretic Factor analysis, Calcium-Transporting ATPases analysis, Cardiomyopathy, Dilated blood, Cardiomyopathy, Dilated pathology, Cricetinae, Cytoskeletal Proteins analysis, Disease Progression, Growth Hormone blood, Growth Hormone therapeutic use, Insulin-Like Growth Factor I analysis, Male, Membrane Glycoproteins analysis, Mesocricetus, Models, Animal, Myocardium metabolism, Myocardium pathology, Sarcoglycans, Sarcoplasmic Reticulum Calcium-Transporting ATPases, Systole, Ventricular Dysfunction, Left blood, Ventricular Dysfunction, Left drug therapy, Ventricular Dysfunction, Left pathology, Cardiomyopathy, Dilated drug therapy, Oligopeptides therapeutic use
Abstract: Objective: The mammalian heart contains specific growth hormone-releasing peptide (GHRP) binding sites whose physiological significance is unknown. We sought to compare the effects of GHRP and GH on progressive left ventricular (LV) dysfunction in the TO-2 hamster model of dilated cardiomyopathy., Methods: TO-2 hamsters (8 weeks old) were injected with GHRP-6 (100 microg/kg day), GH (2 mg/kg day), or saline for 4 weeks; F1B hamsters served as controls. LV functional and structural changes were evaluated by echocardiography and pathology., Results: The increase in body weight of GH-treated TO-2 hamsters was greater than that of animals in the other two groups. Plasma GH and insulin-like growth factor-1 (IGF-1) concentrations were not increased by GHRP-6. LV fractional shortening (LVFS) decreased from 42.0+/-2.6% to 25.4+/-1.8% and the LV end-diastolic dimension (LVDd) increased from 4.0+/-0.1 to 5.0+/-0.1 mm in untreated TO-2 hamsters between 8 and 12 weeks. LVFS was substantially improved by treatment with GHRP-6 (33.4+/-2.0%) or GH (32.0+/-2.1%). The LVDd was significantly smaller in animals treated with GHRP-6 than in those treated with GH. The cross-sectional LV myocyte area and the amount of atrial natriuretic peptide mRNA in the LV were increased by GH but not by GHRP-6. Treatment woth GH at a lower dose (0.2 mg/(kg day)) exerted minimal cardiac and systematic growth effects without improving LV function., Conclusion: GHRP can ameliorate the development of progressive LV dysfunction independently of the GH-IGF-1 axis, suggesting a potential new approach to the heart failure.
Published: 2004
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25. Developmental changes of Ca(2+) handling in mouse ventricular cells from early embryo to adulthood.

Author: Liu W, Yasui K, Opthof T, Ishiki R, Lee JK, Kamiya K, Yokota M, and Kodama I
Subjects: Aging physiology, Animals, Anti-Arrhythmia Agents pharmacology, Calcium Channel Blockers pharmacology, Calcium-Binding Proteins genetics, Calcium-Binding Proteins metabolism, Calcium-Transporting ATPases genetics, Calcium-Transporting ATPases metabolism, Enzyme Inhibitors pharmacology, Female, Heart Ventricles cytology, Heart Ventricles metabolism, Mice, Myocardium cytology, Nisoldipine pharmacology, Patch-Clamp Techniques, Pregnancy, Ryanodine Receptor Calcium Release Channel genetics, Ryanodine Receptor Calcium Release Channel metabolism, Sarcoplasmic Reticulum drug effects, Sarcoplasmic Reticulum metabolism, Sarcoplasmic Reticulum Calcium-Transporting ATPases, Sodium-Calcium Exchanger antagonists & inhibitors, Sodium-Calcium Exchanger genetics, Sodium-Calcium Exchanger metabolism, Thapsigargin pharmacology, Thiourea pharmacology, Calcium metabolism, Heart Ventricles embryology, Heart Ventricles growth & development, Myocardium metabolism, Thiourea analogs & derivatives
Abstract: Transplant of immature cardiomyocytes is recently attracting a great deal of interest as a new experimental strategy for the treatment of failing hearts. Full understanding of normal cardiomyogenesis is essential to make this regenerative therapy feasible. We analyzed the molecular and functional changes of Ca(2+) handling proteins during development of the mouse heart from early embryo at 9.5 days postcoitum (dpc) through adulthood. From the early to the late (18 dpc) embryonic stage, mRNAs estimated by the real time PCR for ryanodine receptor (type 2, RyR2), sarcoplasmic reticulum (SR) Ca(2+) pump (type 2, SERCA2) and phospholamban (PLB) increased by 3-15 fold in the values normalized to GAPDH mRNA, although Na(+)/Ca(2+) exchanger (type 1, NCX1) mRNA was unchanged. After birth, there was a further increase in the mRNAs for RyR2, SERCA2 and PLB by 18-33 fold, but a 50% decrease in NCX1 mRNA. The protein levels of RyR2, SERCA2, PLB and NCX1, which were normalized to total protein, showed qualitatively parallel developmental changes. L-type Ca(2+) channel currents (I(Ca-L)) were increased during the development (1.3-fold at 18 dpc, 2.2-fold at adult stage, vs. 9.5 dpc). At 9.5 dpc, the Ca(2+) transient was, unlike adulthood, unaffected by the SR blockers, ryanodine (5 microM) and thapsigargin (2 microM), and also by a blocker of the Ca(2+) entry via Na(+)/Ca(2+) exchanger, KB-R 7943 (1 microM). The Ca(2+) transient was abolished after application of nisoldipine (5 microM). These results indicate that activator Ca(2+) for contraction in the early embryonic stage depends almost entirely on I(Ca-L).
Published: 2002
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26. Reduced myocardial sarcoplasmic reticulum Ca(2+)-ATPase mRNA expression and biphasic force-frequency relations in patients with hypertrophic cardiomyopathy.

Author: Somura F, Izawa H, Iwase M, Takeichi Y, Ishiki R, Nishizawa T, Noda A, Nagata K, Yamada Y, and Yokota M
Subjects: Adult, Calcium metabolism, Calcium-Transporting ATPases metabolism, Cardiac Pacing, Artificial adverse effects, Cardiomyopathy, Hypertrophic enzymology, Cardiomyopathy, Hypertrophic pathology, Gene Expression Regulation, Enzymologic, Heart Rate physiology, Heart Ventricles pathology, Heart Ventricles physiopathology, Hemodynamics physiology, Humans, Middle Aged, Myocardium pathology, RNA, Messenger genetics, Reverse Transcriptase Polymerase Chain Reaction, Sarcoplasmic Reticulum Calcium-Transporting ATPases, Tachycardia etiology, Tachycardia physiopathology, Ventricular Dysfunction, Left physiopathology, Calcium-Transporting ATPases genetics, Cardiomyopathy, Hypertrophic physiopathology, Myocardium enzymology, RNA, Messenger metabolism
Abstract: Background: The relationship between left ventricular (LV) contractile functional reserve and gene expression of Ca(2+)-handling proteins in patients with hypertrophic cardiomyopathy (HCM) remains to be clarified., Methods and Results: We calculated the maximum first derivative of LV pressure (LV dP/dt(max)) and the LV pressure half-time (T(1/2)) during pacing in 14 patients with nonobstructive HCM (LV ejection fraction >55%) and 7 control subjects. Endomyocardial tissue was obtained, and mRNA levels of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2), ryanodine receptor-2, phospholamban, calsequestrin, and Na(+)/Ca(2+) exchanger were quantified by use of a real-time quantitative reverse transcription-polymerase chain reaction method. Group A consisted of 7 HCM patients who showed a progressive rise in the LV dP/dt(max) with increased heart rate. Group B consisted of 7 HCM patients in whom the heart rate-LV dP/dt(max) relation was biphasic at physiological pacing rates. Both the mean maximal wall thickness and the LV hypertrophy score in group B were greater than in group A (20+/-5 versus 15+/-3 mm and 7+/-1 versus 5+/-2 points, respectively). SERCA2 mRNA levels were significantly lower in group B (SERCA2/GAPDH ratio 0.34+/-0.15) compared with group A (0.72+/-0.27) and control subjects (0.85+/-0.47), whereas the mRNA expression of ryanodine receptor-2, phospholamban, calsequestrin, and Na(+)/Ca(2+) exchanger were similar in all groups., Conclusions: These results suggest that downregulation of SERCA2 mRNA, resulting in altered Ca(2+) handling, may contribute to impaired LV contractile reserve in HCM patients with severe hypertrophy, even in the absence of detectable baseline systolic dysfunction.
Published: 2001
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27. Biphasic changes in left ventricular end-diastolic pressure during dynamic exercise in patients with nonobstructive hypertrophic cardiomyopathy.

Author: Takeichi Y, Yokota M, Iwase M, Izawa H, Nishizawa T, Ishiki R, Somura F, Nagata K, Isobe S, and Noda A
Subjects: Adult, Aged, Blood Pressure, Cardiomyopathy, Hypertrophic blood, Cardiomyopathy, Hypertrophic diagnostic imaging, Catecholamines blood, Diastole, Electrocardiography, Heart drug effects, Heart Rate, Humans, Middle Aged, Myocardial Ischemia diagnosis, Propranolol pharmacology, Ultrasonography, Ventricular Dysfunction, Left blood, Ventricular Dysfunction, Left diagnostic imaging, Cardiomyopathy, Hypertrophic physiopathology, Exercise, Ventricular Dysfunction, Left physiopathology, Ventricular Pressure
Abstract: Objectives: The aim of this study was to clarify the serial changes in left ventricular (LV) end-diastolic pressure (LVEDP) during dynamic exercise in patients with hypertrophic cardiomyopathy (HCM)., Background: Although HCM is characterized by impaired resting LV diastolic function, serial changes in LVEDP during exercise have not been characterized., Methods: We simultaneously measured LV pressure and LV dimensions during symptom-limited supine bicycle exercise in 5 healthy individuals and 20 patients with HCM. Exercise thallium-201 scintigraphic studies were also performed., Results: The LVEDP (baseline: 12 +/- 5 mm Hg) progressively increased to a maximum value at peak exercise (28 +/- 8 mm Hg) in 11 patients with HCM (group I). In the remaining nine patients with HCM (group II), changes in LVEDP during exercise were biphasic, with an initial progressive increase and a subsequent gradual decline up to peak exercise (14 +/- 4 mm Hg at baseline, 27 +/- 5 mm Hg at the critical heart rate, 16 +/- 3 mm Hg at peak exercise). Exercise-induced changes in LV dimensions and LV peak systolic pressures were similar in both groups. However, the maximum first derivative of LV pressure was greater and the LV pressure half-time was shorter in group II than in group I at a similar peak exercise heart rate. The biphasic changes in LVEDP disappeared by pretreatment with propranolol. The LV hypertrophy scores were higher in group I than in group II. Exercise thallium-201 images showed more severe perfusion defects in group I than in group II patients., Conclusions: The biphasic changes in LVEDP seen during exercise may be related to improved coronary microcirculation in response to beta-adrenergic stimulation in patients with mild to moderate HCM.
Published: 2001
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28. Different beta-adrenergic regulation of myocardial contraction and relaxation between apical and nonobstructive hypertrophic cardiomyopathy.

Author: Zuo P, Izawa H, Ishiki R, Noda A, Nishizawa T, Shigemura K, Nagata K, Iwase M, and Yokota M
Subjects: Adult, Cardiac Pacing, Artificial, Cardiomyopathy, Hypertrophic diagnosis, Echocardiography, Exercise Test, Female, Humans, Hypertrophy, Left Ventricular diagnosis, Male, Middle Aged, Reference Values, Systole physiology, Ventricular Function, Left physiology, Cardiomyopathy, Hypertrophic physiopathology, Heart Rate physiology, Hypertrophy, Left Ventricular physiopathology, Myocardial Contraction physiology, Receptors, Adrenergic, beta physiology
Abstract: Background: The impaired adrenergic control of both inotropic and lusitropic reserves has been evaluated in patients with hypertrophic cardiomyopathy (HCM) but not in those with apical HCM (APH)., Objectives: We examined the influence of increases in heart rate and adrenergic stimulation on inotropic and lusitropic reserves in HCM and APH with normal resting left ventricular (LV) systolic function., Methods: We evaluated LV isovolumic contraction and relaxation during atrial pacing and during supine leg exercise in 7 patients with APH and in 8 patients with HCM., Results: Heart rate was significantly correlated with LV isovolumic contraction and relaxation during pacing and exercise in all patients. In all patients with APH, the increase in LV isovolumic contraction was greater during exercise (101%) than pacing alone (27%) for similar increase in heart rate. In 5 patients with HCM, the increase in LV isovolumic contraction was greater during exercise (83%) than pacing alone (24%), whereas in 3 patients with HCM the increase in LV isovolumic contraction was similar between during exercise (25%) and during pacing alone (22%). In all patients with APH, relaxation was shorter during exercise (39%) than pacing alone (16%). Conversely, in patients with HCM relaxation was similarly shortened between during pacing alone (20%) and during exercise (19%)., Conclusions: The force-frequency and the relaxation-frequency relations were well-preserved in all patients. In patients with HCM, the adrenergic enhancement of force-frequency relation and/or relaxation-frequency relation was impaired. In patients with APH, however, adrenergic control of both force-frequency and relaxation-frequency relations was well-preserved, which may indicate a preserved beta-adrenergic signaling pathway.
Published: 2000
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29. Acute effects of a single low oral dose of pimobendan on left ventricular systolic and diastolic function in patients with congestive heart failure.

Author: Ishiki R, Ishihara T, Izawa H, Nagata K, Hirai M, and Yokota M
Subjects: Administration, Oral, Adult, Diastole, Dose-Response Relationship, Drug, Heart Rate drug effects, Heart Ventricles pathology, Heart Ventricles physiopathology, Hemodynamics drug effects, Humans, Male, Middle Aged, Pyridazines blood, Pyridazines metabolism, Systole, Vascular Resistance drug effects, Cardiotonic Agents pharmacology, Heart Failure physiopathology, Heart Ventricles drug effects, Pyridazines pharmacology
Abstract: A recent long-term multicenter trial has shown that pimobendan is more effective when administered in low doses. However, no data are available concerning the effect of a low dose of pimobendan on the systolic and diastolic pressure-volume relations in patients with heart failure. Therefore we examined the effects of a single low dose of oral pimobendan, a calcium sensitizer, on systolic and diastolic hemodynamics in patients with cardiomyopathy and congestive heart failure. We measured the left ventricular (LV) pressure-volume relations using a conductance catheter with a micromanometer tip in 10 patients with chronic congestive heart failure resulting from idiopathic cardiomyopathy before and 45 and 90 min after administration of a single oral dose of 2.5 mg of pimobendan. End-systolic elastance was used as an index of LV contractility and was measured during transient occlusion of the inferior vena cava. End-systolic elastance increased significantly by 25% at 45 min (p < 0.05) and by 55% at 90 min (p < 0.01) without an increase in myocardial oxygen consumption. The inotropic effect was accompanied by improved ventriculoarterial coupling. This effect was attenuated in patients with severely impaired myocardial contractility. LV relaxation, assessed by the time constant of isovolumic pressure decay (T(1/2)), was significantly shortened at 90 min (from 47.7 +/- 1.9 to 41.2 +/- 1.7 ms; p < 0.01), although it remained unchanged at 45 min. The diastolic pressure-volume relation showed a leftward and downward shift in all patients. These results indicate that low-dose oral pimobendan had favorable short-term inotropic and lusitropic effects in patients with congestive heart failure caused by idiopathic dilated cardiomyopathy, and may thus be a useful alternative to traditional agents. Further study in a large-scale trial is merited.
Published: 2000
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30. Impaired force-frequency relations in patients with hypertensive left ventricular hypertrophy. A possible physiological marker of the transition from physiological to pathological hypertrophy.

Author: Inagaki M, Yokota M, Izawa H, Ishiki R, Nagata K, Iwase M, Yamada Y, Koide M, and Sobue T
Subjects: Adrenergic beta-Agonists pharmacology, Adult, Biomarkers, Cardiac Pacing, Artificial, Epinephrine blood, Exercise physiology, Hemodynamics drug effects, Hemodynamics physiology, Humans, Isoproterenol pharmacology, Middle Aged, Myocardial Contraction drug effects, Norepinephrine blood, Tachycardia etiology, Tachycardia physiopathology, Heart Rate physiology, Hypertension complications, Hypertrophy, Left Ventricular etiology, Hypertrophy, Left Ventricular physiopathology, Myocardial Contraction physiology
Abstract: Background: The extent to which force-frequency and relaxation-frequency relations (FFR and RFR, respectively) and exercise-induced adrenergic stimulation affect myocardial inotropic and lusitropic reserves has not been established in patients with left ventricular (LV) hypertrophy (LVH)., Methods and Results: We calculated the maximum first derivative of LV pressure (LV dP/dtmax) and the LV pressure half-time (T1/2) during pacing, exercise, and isoproterenol infusion in 17 patients with hypertensive LVH and 9 control subjects to investigate the influence of increases in heart rate (HR) and adrenergic stimulation on inotropic and lusitropic reserves. Group A consisted of 10 LVH patients who showed a progressive increase in the HR-LV dP/dtmax relation. Group B consisted of 7 LVH patients in whom the HR-dP/dtmax relation at physiological pacing rates was biphasic. The LV mass index was larger and the LV ejection fraction was smaller in group B than in group A (244+/-72 g/m2 versus 172+/-22 g/m2 and 55+/-18% versus 72+/-6%, respectively; both P<0.05). The increase in LV dP/dtmax was greater during exercise than pacing alone for similar increases in HR in all groups (P<0.05) (group A, 111+/-22% versus 25+/-14%; group B, 105+/-35% versus 14+/-10%; control, 111+/-24% versus 25+/-12%). T1/2 was shorter (P<0.05) during exercise than with pacing alone in all groups (group A, 41+/-6% versus 11+/-3%; group B, 38+/-9% versus 14+/-4%; control, 44+/-6% versus 12+/-5%). Isoproterenol infusion caused similar increases in LV dP/dtmax and similar decreases in T1/2 in all groups., Conclusions: The FFR was biphasic in patients with severe LVH irrespective of LV function but was preserved in patients with less severe LVH and control subjects. Importantly, the RFR and adrenergic control of both inotropic and lusitropic reserves were well preserved in all LVH patients. A biphasic FFR at physiological pacing rates may be one of the earliest markers of the transition from physiological adaptation to the pathological process in LVH patients.
Published: 1999
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31. A Japanese family carrying a novel mutation in the Emery-Dreifuss muscular dystrophy gene.

Author: Ichikawa Y, Watanabe M, Kowa H, Murayama S, Mizuno T, Komuro I, Ishiki R, Goto J, and Kanazawa I
Subjects: Adolescent, Adult, Amino Acid Sequence, Female, Humans, Male, Nuclear Proteins, Pedigree, Polymerase Chain Reaction, Frameshift Mutation, Membrane Proteins genetics, Muscular Dystrophies genetics, Thymopoietins genetics
Abstract: We report on a Japanese family affected by Emery-Dreifuss muscular dystrophy carrying a novel mutation of the emerin (STA) gene. The cardinal clinical feature of the family was cardiac conduction block and mild myopathy. A deletion of 11 bp with a frameshift was identified in exon 6, causing truncation of the predicted protein. The relationship between mutation and phenotype is discussed.
Published: 1997
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32. Patency of intermediate size side branches after Palmaz-Schatz stent implantation.

Author: Ishiki R, Hara K, Ikari Y, Yamasaki M, Yamaguchi T, and Tamura T
Subjects: Angioplasty, Balloon, Coronary, Coronary Angiography, Coronary Disease pathology, Coronary Disease physiopathology, Coronary Vessels pathology, Follow-Up Studies, Humans, Coronary Disease therapy, Stents adverse effects, Vascular Patency
Abstract: The immediate and long-term patency of intermediate size side branches was assessed by serial coronary angiography in 47 patients with 48 lesions to determine whether the presence of these side branches (1-2 mm in diameter) is unsuitable for Palmaz-Schatz stent implantation. Coronary angiography was performed at baseline, after conventional balloon angioplasty, immediately after stent implantation, at 1 week, and at 6-month follow-up. Sixty-eight lesion-associated side branches that were 1-2 mm in diameter, 11 with branch ostial stenosis (Group A) and 57 without ostial stenosis (Group B) were studied. After stent implantation, 9 (13%) branches became totally occluded and coronary flow deteriorated in 13 branches (19%). The incidence of side branch occlusion during the procedure in group A was greater than in group B (55% vs. 12%; p < 0.005). One (2%) patient suffered persistent chest pain, but no procedure was complicated by Q-wave myocardial infarction or significant elevation of creatine kinase concentration. Flow improved in 82% of the occluded side branches after 1 week and in 90% after 6 months. These results suggest that the presence of intermediate size side branches is not a contra-indication to Palmaz-Schatz stent implantation.
Published: 1997
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33. Depressed mechanoenergetics and compensatory responses in idiopathic dilated cardiomyopathy.

Author: Ishihara H, Yokota M, Kato R, Kanda H, Ichihara S, Fujimura T, Takeichi Y, Ishiki R, Inagaki M, Izawa H, Machii T, Iwase M, and Sobue T
Subjects: Blood Pressure, Cardiac Output, Humans, Oxygen Consumption, Ventricular Pressure, Cardiomyopathy, Dilated physiopathology, Energy Metabolism, Myocardial Contraction, Ventricular Function, Left
Abstract: The aim of this study was to clarify that the depressed mechanoenergetics in patients with idiopathic dilated cardiomyopathy (DCM) resulted from compensation for the decreased contractility. The study population consisted of eight control subjects, with normal left ventricular size and ejection fraction and 31 patients with DCM. Left ventricular end-systolic elastance (Ees), effective arterial elastance (Ea), external work (EW), and the pressure-volume area (PVA) were measured, using a dual-field volume conductance catheter equipped with a micromanometer-tipped catheter. Ea/Ees was evaluated as ventriculoarterial coupling. Normal hearts worked at almost optimal condition (defined as Ea/Ees = 1/2), while ventriculoarterial coupling was far from the optimum (Ea > Ees) in patients with DCM. Ees in patients with DCM was less than that in control subjects; however, Ea was similar in the two groups. The mismatch of Ea/Ees observed in DCM leads to depressed mechanoenergetics as a result of the compensatory response to maintain adequate blood pressure. Volume enlargement plays an important role in maintaining adequate blood pressure and cardiac output in the course of chronic deterioration of contractility.
Published: 1997

34. [Outcome of coronary angioplasty and coronary artery bypass grafting in patients over 75 years old].

Author: Somitsu Y, Yamaguchi T, Ishiki R, Ikari Y, Furuta Y, Hara K, Saeki F, Tamura T, Wanibuchi Y, and Suma H
Subjects: Aged, Aged, 80 and over, Coronary Disease mortality, Coronary Disease surgery, Coronary Disease therapy, Female, Follow-Up Studies, Humans, Male, Prognosis, Survival Rate, Treatment Outcome, Angioplasty, Balloon, Coronary, Coronary Artery Bypass
Abstract: Mortality, morbidity, and 3-year survival rates were evaluated in patients aged over 75 years undergoing initial revascularization by percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG). The groups of 74 patients undergoing PTCA and 27 undergoing CABG had similar clinical characteristics including age, sex, emergency operation, prior myocardial infarction, and ejection fraction. The PTCA group contained significantly more patients with single vessel disease (44% vs 8%, p < 0.01) while the CABG group had more three-vessel or left main trunk disease (30% vs 70%, p < 0.01). The patients in the PTCA group demonstrated more prior cerebral vascular events, renal insufficiency, and abdominal aortic aneurysms. Angiographic revascularization was achieved in 112 of 130 lesions (86%) and in 63 of the 74 (84%) patients in the PTCA group. Hospital mortality for the PTCA group was 5.4% (two cardiac deaths and two non-cardiac deaths), but 0% for the CABG group. Myocardial infarction occurred in 1.3% and 3.7%, respectively (p = NS). Three-year survival, excluding hospital deaths, was 90% for patients with PTCA and 96% for those with CABG (p = NS). All these deaths were of non-cardiac origin. Both PTCA and CABG are safe and effective for selected patients over the age of 75 years.
Published: 1994

35. Quinolinic acid: an endogenous inhibitor specific for type B monoamine oxidase in human brain synaptosomes.

Author: Naoi M, Ishiki R, Nomura Y, Hasegawa S, and Nagatsu T
Subjects: Brain drug effects, Humans, In Vitro Techniques, Quinolinic Acid, Structure-Activity Relationship, Synaptosomes enzymology, Brain enzymology, Isoenzymes antagonists & inhibitors, Monoamine Oxidase Inhibitors, Pyridines pharmacology, Quinolinic Acids pharmacology
Abstract: Quinolinic acid (QUIN), a well-known excitotoxin, was found to inhibit type B monoamine oxidase (MAO-B) in human brain synaptosomal mitochondria. By kinetic analysis, the inhibition of MAO-B activity by QUIN was competitive with the substrate, kynuramine. On the other hand, type A MAO (MAO-A) activity in human brain synaptosomal mitochondria and human placental mitochondria was not affected by QUIN. The selective inhibition of MAO-B by QUIN was confirmed using human liver mitochondria; only MAO-B was inhibited by QUIN and MAO-A was not inhibited. The inhibition was completely reversible. Among compounds structurally related to QUIN, 4-pyrimidine carboxaldehyde was the most potent substrate-competitive inhibitor of MAO-B, while 3-hydroxyanthranilic acid and xanthrenic acid, other metabolites of tryptophan, inhibited MAO non-competitively with the substrate. The inhibition of MAO-B by QUIN may be related to the causes of the neurotoxicity of QUIN.
Published: 1987
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36. 4-(O-benzylphenoxy)-N-methylbutylamine (bifemelane) and other 4-(O-benzylphenoxy)-N-methylalkylamines as new inhibitors of type A and B monoamine oxidase.

Author: Naoi M, Nomura Y, Ishiki R, Suzuki H, and Nagatsu T
Subjects: Adrenal Gland Neoplasms enzymology, Animals, Antidepressive Agents, Binding, Competitive, Brain enzymology, Chemical Phenomena, Chemistry, Female, Humans, Kynuramine metabolism, Mitochondria, Liver enzymology, Monoamine Oxidase metabolism, Pheochromocytoma enzymology, Placenta enzymology, Pregnancy, Rats, Structure-Activity Relationship, Synaptosomes enzymology, Tumor Cells, Cultured, Benzhydryl Compounds pharmacology, Monoamine Oxidase Inhibitors pharmacology
Abstract: 4-(O-Benzylphenoxy)-N-methylbutylamine (Bifemelane, BP-N-methylbutylamine), a new psychotropic drug, was found to inhibit monoamine oxidase (MAO) in human brain synaptosomes. It inhibited type A MAO (MAO-A) competitively and type B (MAO-B) noncompetitively. BP-N-methylbutylamine had a much higher affinity to MAO-A than an amine substrate, kynuramine, and it was a more potent inhibitor of MAO-A than of MAO-B. The Ki values of MAO-A and -B were determined to be 4.20 and 46.0 microM, respectively, while the Km values of MAO-A and -B with kynuramine were 44.1 and 90.0 microM, respectively. The inhibition of MAO-A and -B by BP-N-methylbutylamine was found to be reversible by dialysis of the incubation mixture. MAO-A in human placental and liver mitochondria and in a rat clonal pheochromocytoma cell line, PC12h, was inhibited competitively by BP-N-methylbutylamine, while MAO-B in human liver mitochondria was inhibited noncompetitively, as in human brain synaptosomes. BP-N-methylbutylamine was not oxidized by MAO-A and -B. The effects of other BP-N-methylalkylamines, such as BP-N-methylethylamine, -propylamine, and -pentanylamine, on MAO activity were examined. BP-N-methylbutylamine was the most potent inhibitor of MAO-A, and BP-N-methylethylamine and -propylamine inhibited MAO-B competitively, whereas BP-N-methylbutylamine and -pentanylamine inhibited it noncompetitively. Inhibition of these BP-N-methylalkylamines on MAO-A and -B is discussed in relation to their chemical structure.
Published: 1988
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37. 1,4-Benzoquinone as a new inhibitor of monoamine oxidase.

Author: Naoi M, Nomura Y, Ishiki R, Suzuki H, and Nagatsu T
Subjects: Adrenal Gland Neoplasms enzymology, Animals, Clone Cells enzymology, Humans, Kinetics, Kynuramine metabolism, Mitochondria, Liver enzymology, Pheochromocytoma enzymology, Placenta enzymology, Rats, Benzoquinones, Isoenzymes metabolism, Monoamine Oxidase metabolism, Monoamine Oxidase Inhibitors pharmacology, Quinones pharmacology
Abstract: The effect of 1,4-benzoquinone (BQ) on type A and B monoamine oxidase (MAO-A and -B) in human brain synaptosomes was examined. MAO-A was found to be markedly inhibited by BQ competitively with the substrate, kynuramine, while MAO-B was less sensitive to this inhibitor and the inhibition was non-competitive with the substrate. The Ki value of MAO-A (9.62 +/- 0.35 microM) was much smaller than the Km value of the enzyme with the substrate (56.3 +/- 3.5 microM) or the Ki value of MAO-B with BQ (20.3 +/- 0.9 microM). The inhibition of MAO-A by BQ was also confirmed by the use of platelet mitochondria and clonal rat pheochromocytoma PC12h cells as enzyme sources. The inhibition of MAO activity by BQ proved to be reversible: the inhibited enzyme activity could be recovered by column chromatography on Sephadex G-25.
Published: 1987
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