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29 results on '"Cappola, T"'

1. A pharmacogenetic investigation of intravenous furosemide in decompensated heart failure: a meta-analysis of three clinical trials

Author: de Denus, S, Rouleau, J L, Mann, D L, Huggins, G S, Cappola, T P, Shah, S H, Keleti, J, Zada, Y F, Provost, S, Bardhadi, A, Phillips, M S, Normand, V, Mongrain, I, and Dubé, M-P
Published: 2017
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2. Baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF)

Author: McMurray, John J.V., Anand, Inder S., Diaz, Rafael, Maggioni, Aldo P., OʼConnor, Christopher, Pfeffer, Marc A., Solomon, Scott D., Tendera, Michal, van Veldhuisen, Dirk J., Albizem, Moetaz, Cheng, Sunfa, Scarlata, Debra, Swedberg, Karl, Young, James B., Amuchastegui, M., Belziti, C., Bluguermann, J., Caccavo, M., Cartasegna, L., Colque, R., Cuneo, C., Fernandez, A., Gabito, A., Goicochea, R., Gonzalez, M., Gorosito, V., Grinfeld, L., Hominal, M., Kevorkian, R., Litvak Bruno, M., Llanos, J., Mackinnon, I., Manuale, O., Marzetti, E., Nul, D., Perna, E., Riccitelli, M., Sanchez, A., Santos, D., Schygiel, P., Toblli, J., Vogel, D., Aggarwal, A., Amerena, J., De Looze, F., Fletcher, P., Hare, D., Ireland, M., Krum, H., Lattimore, J., Marwick, T., Sindone, A., Thompson, P., Waites, J., Altenberger, J., Ebner, C., Lenz, K., Pacher, R., Poelzl, G., Charlier, F., de Ceuninck, M., De Keulenaer, G., Dendale, P., Maréchal, P., Mullens, W., Thoeng, J., Vanderheyden, M., Vanhaecke, J., Weytjens, C., Wollaert, B., Albuquerque, D., Almeida, D., Aspe y Rosas, J., Bocchi, E., Bordignon, S., Clausell, N., Kaiser, S., Leaes, P., Martins Alves, S., Montera, M., Moura, L., Pereira de Castro, R., Rassi, S., Reis, A., Saraiva, J., Simões, M., Souza Neto, J., Teixeira, M., Benov, H., Chompalova, B., Donova, T., Georgiev, P., Gotchev, D., Goudev, A., Grigorov, M., Guenova, D., Hergeldjieva, V., Ivanov, D., Kostova, E., Manolova, A., Marchev, S., Nikolov, F., Popov, A., Raev, D., Tzekova, M., Czarnecki, W., Giannetti, N., Haddad, H., Heath, J., Huynh, T., Lepage, S., Liu, P., Lonn, E., Ma, P., Manyari, D., Moe, G., Parker, J., Pesant, Y., Rajda, M., Ricci, J., Roth, S., Sestier, F., Sluzar, V., Sussex, B., Vizel, S., Antezana, G., Bugueno, C., Castro, P., Conejeros, C., Manriquez, L., Martinez, D., Potthoff, S., Stockins, B., Vukasovic, J., Gregor, P., Herold, M., Jerabek, O., Jirmar, R., Kuchar, R., Linhart, A., Podzemska, B., Soucek, M., Spac, J., Spacek, R., Vodnansky, P., Bronnum-Schou, J., Clemmensen, K., Egstrup, K., Jensen, G., Kjoller-Hansen, L., Kober, L., Markenvard, J., Rokkedal, J., Skagen, K., Torp-Pedersen, C., Tuxen, C., Videbak, L., Laks, T., Vahula, V., Harjola, V., Kettunen, R., Kotila, M., Bauer, F., Cohen Solal, A., Coisne, D., Davy, J., De Groote, P., Dos Santos, P., Funck, F., Galinier, M., Gibelin, P., Isnard, R., Neuder, Y., Roul, G., Sabatier, R., Trochu, J., Anker, S., Denny, S., Dreykluft, T., Flesch, M., Genth-Zotz, S., Hambrecht, R., Hein, J., Jeserich, M., John, M., Kreider-Stempfle, H., Laufs, U., Muellerleile, K., Natour, M., Sandri, M., Schäufele, T., von Hodenberg, E., Weyland, K., Winkelmann, B., Tse, H., Yan, B., Barsi, B., Csikasz, J., Dezsi, C., Edes, I., Forster, T., Karpati, P., Kerekes, C., Kis, E., Kosa, I., Lupkovics, G., Nagy, A., Preda, I., Ronaszeki, A., Tomcsanyi, J., Zamolyi, K., Agarwal, D., Bahl, V., Bordoloi, A., Chockalingam, K., Chopda, M., Chopra, V., Dugal, J., Ghaisas, N., Ghosh, S., Grant, P., Hiremath, S., Iyengar, S., Jagadeesa Subramania, B., Jain, P., Joshi, A., Khan, A., Mullasari, A., Naik, S., Oomman, A., Pai, V., Pareppally Gopal, R., Parikh, K., Patel, T., Prakash, V., Sastry, B., Sathe, S., Sinha, N., Srikanthan, V., Subburamakrishnan, P., Thacker, H., Wander, G., Admon, D., Katz, A., Klainman, E., Lewis, B., Marmor, A., Moriel, M., Mosseri, M., Shotan, A., Weinstein, J., Zimlichman, R., Agostoni, P., Albanese, M., Alunni, G., Bini, R., Boccanelli, A., Bolognese, L., Campana, C., Carbonieri, E., Carpino, C., Checco, L., Cosmi, F., DʼAngelo, G., De Cristofaro, M., Floresta, A., Fucili, A., Galvani, M., Ivleva, A., Marra, S., Musca, G., Peccerillo, N., Perrone Filardi, P., Picchio, E., Russo, T., Scelsi, L., Senni, M., Tavazzi, L., Erglis, A., Jasinkevica, I., Kakurina, N., Veze, I., Volans, E., Bagdonas, A., Berukstis, E., Celutkiene, J., Dambrauskaite, A., Jarasuniene, D., Luksiene, D., Rudys, A., Sakalyte, G., Sliaziene, S., Aguilar-Romero, R., Cardona-Muñoz, E., Castro-Jimenez, J., Chavez-Herrera, J., Chuquiure Valenzuela, E., De la Pena, G., Herrera, E., Leiva-Pons, J., Lopez Alvarado, A., Mendez Machado, G., Ramos-Lopez, G., Basart, D., Buijs, E., Cornel, J., de Leeuw, M., Dijkgraaf, R., Dunselman, P., Freericks, M., Hamraoui, K., Lenderlink, T., Linssen, G., Lodewick, P., Lodewijks, C., Lok, D., Nierop, P., Ronner, E., Somsen, A., van Dantzig, J., van der Burgh, P., van Kempen, L., van Vlies, B., Voors, A., Wardeh, A., Willems, F., Dickstein, K., Gundersen, T., Hole, T., Thalamus, J., Westheim, A., Dabrowski, M., Gorski, J., Korewicki, J., Kuc, K., Miekus, P., Musial, W., Niegowska, J., Piotrowski, W., Podolec, P., Polonski, L., Ponikowski, P., Rynkiewicz, A., Szelemej, R., Trusz-Gluza, M., Ujda, M., Wojciechowski, D, Wysokinski, A., Camacho, A., Fonseca, C., Monteiro, P., Apetrei, E., Bruckner, I., Carasca, E., Coman, I., Datcu, M., Dragulescu, S., Ionescu, P., Iordachescu-Petica, D., Manitiu, I., Popa, V., Pop-Moldovan, A., Radoi, M., Stamate, S., Tomescu, M., Vita, I., Aroutiounov, G., Ballyuzek, M., Bart, B., Churina, S., Glezer, M., Goloshchekin, B., Ivleva, A., Kobalava, Z., Kostenko, V., Lopatin, Y., Martynov, A., Orlov, V., Semernin, E., Shogenov, Z., Sidorenko, B., Skvortsov, A., Storzhakov, G., Sulimov, V., Talibov, O., Tereshenko, S., Tsyrline, V., Zadionchenko, V., Zateyshchikov, D., Dzupina, A., Hranai, M., Kmec, J., Micko, K., Murin, J., Pella, D., Sojka, G., Spisak, V., Vahala, P., Vinanska, D., Badat, A., Bayat, J., Dawood, S., Delport, E., Ellis, G., Garda, R., Klug, E., Mabin, T., Naidoo, D., Pretorius, M., Ranjith, N., Van Zyl, L., Weich, H., Anguita, M., Berrazueta, J., Bruguera i Cortada, J., de Teresa, E., Gómez Sánchez, M., González Juanatey, J., Gonzalez-Maqueda, I., Jordana, R., Lupon, J., Manzano, L., Pascual Figal, D., Pulpón, L., Recio, J., Ridocci Soriano, F., Rodríguez Lambert, J., Roig Minguell, E., Roig Minguell, E., Romero, J., Valdovinos, P., Klintberg, L., Kronvall, T., Lycksell, M., Morner, S., Rydberg, E., Swedberg, K., Timberg, I., Wikstrom, G., Moccetti, T.4, Ashok, J., Banerjee, P., Carr-White, G., Cleland, J., Connolly, E., Francis, M., Greenbaum, R., Kadr, H., Lindsay, S., McMurray, J., Megarry, S., Memon, A., Murdoch, D., Senior, R., Squire, I., Tan, L., Witte, K., Adams, K., Adamson, P., Adler, A., Altschul, L., Altschuller, A., Amirani, H., Anand, I., Andreou, C., Ansari, M., Antonishen, M., Banchs, H., Banerjee, S., Banish, D., Bank, A., Barbagelata, A., Barnard, D., Bellinger, R., Benn, A., Berk, M., Berry, B., Bethala, V., Bilazarian, S., Bisognano, J., Bleyer, F., Blum, M., Boehmer, J., Bouchard, A., Boyle, A., Bozkurt, B., Brown, C., Burlew, B., Burnham, K., Butler, J., Call, J., Cambier, P., Cappola, T., Carlson, R., Chandler, B., Chandra, R., Chandraratna, P., Chernick, R., Colan, D., Colfer, H., Colucci, W., Connelly, T., Costantini, O., Dadkhah, S., Dauber, I., Davis, J., Davis, S., Denning, S., Drazner, M., Dunlap, S., Egbujiobi, L., Elkayam, U., Elliott, J., El-Shahawy, M., Essandoh, L., Ewald, G., Fang, J., Farhoud, H., Felker, G., Fernandez, J., Festin, R., Fishbein, G., Florea, V., Flores, E., Floro, J., Gabris, M., Garg, M., Gatewood, R., Geller, M., Ghali, J., Ghumman, W., Gibbs, G., Gillespie, E., Gilmore, R., Gogia, H., Goldberg, L., Gradus-Pizlo, I., Grainger, T., Gudmundsson, G., Gunawardena, D., Gupta, D., Hack, T., Hall, S., Hamroff, G., Hankins, S., Hanna, M., Hargrove, J., Haught, W., Hauptman, P., Hazelrigg, M., Herzog, C., Heywood, J., Hill, T., Hilton, T., Hirsch, H., Hunter, J., Ibrahim, H., Imburgia, M., Iteld, B., Jackson, B., Jaffrani, N., Jain, D., Jain, A., James, M., Jimenez, J., Johnson, E., Kale, P., Kaneshige, A., Kapadia, S., Karia, D., Karlsberg, R., Katholi, R., Kerut, E., Khoury, W., Kipperman, R., Klapholz, M., Kosinski, E., Kozinn, M., Kraus, D., Krueger, S., Krum, H., Kumar, S., Lader, E., Lee, C., Levy, W., Lewis, E., Light-McGroary, K., Loh, I., Lombardi, W., Machado, C., Maislos, F., Mancini, D., Markus, T., Mather, P., McCants, K., McGrew, F., McLaurin, B., McMillan, E., McNamara, D., Meyer, T., Meymandi, S., Miller, A., Minami, E., Modi, M., Mody, F., Mohanty, P., Moscoso, R., Moskowitz, R., Moustafa, M., Mullen, M., Naz, T., Noonan, T., OʼBrien, T., Oellerich, W., Oren, R., Pamboukian, S., Pereira, N., Pitt, W., Porter, C., Prabhu, S., Promisloff, S., Ratkovec, R., Richardson, R., Ross, A., Saleh, N., Saltzberg, M., Sarkar, S., Schmedtje, J., Schneider, R., Schuyler, G., Shanes, J., Sharma, A., Siegel, C., Siegel, R., Silber, D., Singh, V., Singh, N., Singh, J., Sklar, J., Small, R., Smith, A., Smith, E., Smith, E., Smull, D., Sotolongo, R., Staniloae, C., Stapleton, D., Steele, P., Stehlik, J., Stein, M., Tang, W., Thadani, U., Torre-Amoine, G., Trichon, B., Tsai, C., Tummala, R., Van Bakel, A., Vicari, R., Vijay, N., Vijayaraghavan, K., Vittorio, T., Vossler, M., Wagoner, L., Wallis, D., Ward, N., Widmer, M., Wight, J., Wilkins, C., Williams, C., Williams, G., Winchester, M., Winkel, E., Wittmer, B., Wood, D., Wormer, D., Wright, R., Xu, Z., Yasin, M., and Zolty, R.
Published: 2013
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3. Treatment of Anemia with Darbepoetin Alfa in Systolic Heart Failure

Author: Karl Swedberg, James B. Young, Inder S. Anand, Sunfa Cheng, Akshay S. Desai, Rafael Diaz, Aldo P. Maggioni, John J. V. McMurray, Christopher O'Connor, Marc A. Pfeffer, Scott D. Solomon, Yan Sun, Michal Tendera, Dirk J. van Veldhuisen, Young J, Grinfeld L, Krum H, Vanhaecke J, Olivera Clausell N, Goudev A, Howlett J, Corbalan R, Hradec J, Kober L, Eha J, Cohen Solal A, Anker SD, Chopra V, Lewis B, Erglis A, Sakalyte G, Cardona Munoz E, Dunselman P, Dickstein K, Ponikowski P, Seabra Gomes R, Apetrei E, Mareev V, Murin J, Dalby A, Lopez Sendon J, Willenheimer R, Cleland J, Adams K, Anand I, Butler J, Dunlap M, Felker M, Ghali J, Levy W, Carson P, Cohn J, Drexler H, Pocock S, Ryden L, Poole Wilson P, Fishbane S, Ivanovich P, Nissenson A, Katz S, Barkoudah E, Campbell P, Desai A, Finn PV, Hartley L, Kasabov R, Odutayo KA, Rajesh V, Solomon S, Weinrauch LA, Albizem M, Cheng S, Chou W, Deegenaars M, Dougherty M, Fouqueray B, Froissart M, Froment A, Gadd S, Ghosh S, Grazette L, Guillet S, Gulabani D, Haddock B, Harris C, Jaffer A, Kerns C, Kim J, Knussel B, Law H, Mather R, Mix C, Moore L, Moyes R, Polu K, Rossert J, Scarlata D, Smirnakis K, Smith L, Snyder W, Sun Y, Trotman ML, Wasserman S, Watkins A, Wong M, Zhang Y, Amuchastegui M, Belziti C, Bluguermann J, Caccavo M, Cartasegna L, Colque R, Cuneo C, Fernandez A, Gabito A, Goicochea R, Gonzalez M, Gorosito V, Hominal M, Kevorkian R, Litvak Bruno M, Llanos J, Mackinnon I, Manuale O, Marzetti E, Nul D, Perna E, Riccitelli M, Sanchez A, Santos D, Schygiel P, Toblli J, Vogel D, Aggarwal A, Amerena J, De Looze F, Fletcher P, Hare D, Ireland M, Lattimore J, Marwick T, Sindone A, Thompson P, Waites J, Altenberger J, Ebner C, Lenz K, Pacher R, Poelzl G, Charlier F, de Ceuninck M, De Keulenaer G, Dendale P, Maréchal P, Mullens W, Thoeng J, Vanderheyden M, Weytjens C, Wollaert B, Albuquerque D, Almeida D, Aspe y. Rosas J, Bocchi E, Bordignon S, Clausell N, Kaiser S, Leaes P, Martins Alves S, Montera M, Moura L, Pereira de Castro R, Rassi S, Reis A, Saraiva J, Simões M, Souza Neto J, Teixeira M, Benov H, Chompalova B, Donova T, Georgiev P, Gotchev D, Grigorov M, Guenova D, Hergeldjieva V, Ivanov D, Kostova E, Manolova A, Marchev S, Nikolov F, Popov A, Raev D, Tzekova M, Czarnecki W, Giannetti N, Haddad H, Heath J, Huynh T, Lepage S, Liu P, Lonn E, Ma P, Manyari D, Moe G, Parker J, Pesant Y, Rajda M, Ricci J, Roth S, Sestier F, Sluzar V, Sussex B, Vizel S, Antezana G, Bugueno C, Castro P, Conejeros C, Manriquez L, Martinez D, Potthoff S, Stockins B, Vukasovic J, Gregor P, Herold M, Jerabek O, Jirmar R, Kuchar R, Linhart A, Podzemska B, Soucek M, Spac J, Spacek R, Vodnansky P, Bronnum Schou J, Clemmensen K, Egstrup K, Jensen G, Kjoller Hansen L, Markenvard J, Rokkedal J, Skagen K, Torp Pedersen C, Tuxen C, Videbak L, Laks T, Vahula V, Harjola V, Kettunen R, Kotila M, Bauer F, Coisne D, Davy J, De Groote P, Dos Santos P, Funck F, Galinier M, Gibelin P, Isnard R, Neuder Y, Roul G, Sabatier R, Trochu J, Denny S, Dreykluft T, Flesch M, Genth Zotz S, Hambrecht R, Hein J, Jeserich M, John M, Kreider Stempfle H, Laufs U, Muellerleile K, Natour M, Sandri M, Schäufele T, von Hodenberg E, Weyland K, Winkelmann B, Tse H, Yan B, Barsi B, Csikasz J, Dezsi C, Edes I, Forster T, Karpati P, Kerekes C, Kis E, Kosa I, Lupkovics G, Nagy A, Preda I, Ronaszeki A, Tomcsanyi J, Zamolyi K, Agarwal D, Bahl V, Bordoloi A, Chockalingam K, Chopda M, Dugal J, Ghaisas N, Grant P, Hiremath S, Iyengar S, Jagadeesa Subramania B, Jain P, Joshi A, Khan A, Mullasari A, Naik S, Oomman A, Pai V, Pareppally Gopal R, Parikh K, Patel T, Prakash V, Sastry B, Sathe S, Sinha N, Srikanthan V, Subburamakrishnan P, Thacker H, Wander G, Admon D, Katz A, Klainman E, Marmor A, Moriel M, Mosseri M, Shotan A, Weinstein J, Zimlichman R, Agostoni P, Albanese M, Alunni G, Bini R, Boccanelli A, Bolognese L, Campana C, Carbonieri E, Carpino C, Checco L, Cosmi F, Angelo GD, De Cristofaro M, Floresta A, Fucili A, Galvani M, Ivleva A, Marra S, Musca G, Peccerillo N, Picchio E, Russo T, Scelsi L, Senni M, Tavazzi L, Jasinkevica I, Kakurina N, Veze I, Volans E, Bagdonas A, Berukstis E, Celutkiene J, Dambrauskaite A, Jarasuniene D, Luksiene D, Rudys A, Sliaziene S, Aguilar Romero R, Cardona Muñoz E, Castro Jimenez J, Chavez Herrera J, Chuquiure Valenzuela E, De la Pena G, Herrera E, Leiva Pons J, Lopez Alvarado A, Mendez Machado G, Ramos Lopez G, Basart D, Buijs E, Cornel J, de Leeuw M, Dijkgraaf R, Freericks M, Hamraoui K, Lenderlink T, Linssen G, Lodewick P, Lodewijks C, Lok D, Nierop P, Ronner E, Somsen A, van Dantzig J, van der Burgh P, van Kempen L, van Vlies B, Voors A, Wardeh A, Willems F, Gundersen T, Hole T, Thalamus J, Westheim A, Dabrowski M, Gorski J, Korewicki J, Kuc K, Miekus P, Musial W, Niegowska J, Piotrowski W, Podolec P, Polonski L, Rynkiewicz A, Szelemej R, Trusz Gluza M, Ujda M, Wojciechowski D, Wysokinski A, Camacho A, Fonseca C, Monteiro P, Bruckner I, Carasca E, Coman I, Datcu M, Dragulescu S, Ionescu P, Iordachescu Petica D, Manitiu I, Popa V, Pop Moldovan A, Radoi M, Stamate S, Tomescu M, Vita I, Aroutiounov G, Ballyuzek M, Bart B, Churina S, Glezer M, Goloshchekin B, Kobalava Z, Kostenko V, Lopatin Y, Martynov A, Orlov V, Semernin E, Shogenov Z, Sidorenko B, Skvortsov A, Storzhakov G, Sulimov V, Talibov O, Tereshenko S, Tsyrline V, Zadionchenko V, Zateyshchikov D, Dzupina A, Hranai M, Kmec J, Micko K, Pella D, Sojka G, Spisak V, Vahala P, Vinanska D, Badat A, Bayat J, Dawood S, Delport E, Ellis G, Garda R, Klug E, Mabin T, Naidoo D, Pretorius M, Ranjith N, Van Zyl L, Weich H, Anguita M, Berrazueta J, Bruguera i. Cortada J, de Teresa E, Gómez Sánchez M, González Juanatey J, Gonzalez Maqueda I, Jordana R, Lupon J, Manzano L, Pascual Figal D, Pulpón L, Recio J, Ridocci Soriano F, Rodríguez Lambert J, Roig Minguell E, Romero J, Valdovinos P, Klintberg L, Kronvall T, Lycksell M, Morner S, Rydberg E, Swedberg K, Timberg I, Wikstrom G, Moccetti T, Ashok J, Banerjee P, Carr White G, Connolly E, Francis M, Greenbaum R, Kadr H, Lindsay S, McMurray J, Megarry S, Memon A, Murdoch D, Senior R, Squire I, Tan L, Witte K, Adamson P, Adler A, Altschul L, Altschuller A, Amirani H, Andreou C, Ansari M, Antonishen M, Banchs H, Banerjee S, Banish D, Bank A, Barbagelata A, Barnard D, Bellinger R, Benn A, Berk M, Berry B, Bethala V, Bilazarian S, Bisognano J, Bleyer F, Blum M, Boehmer J, Bouchard A, Boyle A, Bozkurt B, Brown C, Burlew B, Burnham K, Call J, Cambier P, Cappola T, Carlson R, Chandler B, Chandra R, Chandraratna P, Chernick R, Colan D, Colfer H, Colucci W, Connelly T, Costantini O, Dadkhah S, Dauber I, Davis J, Davis S, Denning S, Drazner M, Dunlap S, Egbujiobi L, Elkayam U, Elliott J, El Shahawy M, Essandoh L, Ewald G, Fang J, Farhoud H, Felker G, Fernandez J, Festin R, Fishbein G, Florea V, Flores E, Floro J, Gabris M, Garg M, Gatewood R, Geller M, Ghumman W, Gibbs G, Gillespie E, Gilmore R, Gogia H, Goldberg L, Gradus Pizlo I, Grainger T, Gudmundsson G, Gunawardena D, Gupta D, Hack T, Hall S, Hamroff G, Hankins S, Hanna M, Hargrove J, Haught W, Hauptman P, Hazelrigg M, Herzog C, Heywood J, Hill T, Hilton T, Hirsch H, Hunter J, Ibrahim H, Imburgia M, Iteld B, Jackson B, Jaffrani N, Jain D, Jain A, James M, Jimenez J, Johnson E, Kale P, Kaneshige A, Kapadia S, Karia D, Karlsberg R, Katholi R, Kerut E, Khoury W, Kipperman R, Klapholz M, Kosinski E, Kozinn M, Kraus D, Krueger S, Kumar S, Lader E, Lee C, Lewis E, Light McGroary K, Loh I, Lombardi W, Machado C, Maislos F, Mancini D, Markus T, Mather P, McCants K, McGrew F, McLaurin B, McMillan E, McNamara D, Meyer T, Meymandi S, Miller A, Minami E, Modi M, Mody F, Mohanty P, Moscoso R, Moskowitz R, Moustafa M, Mullen M, Naz T, Noonan T, O. Brien T, Oellerich W, Oren R, Pamboukian S, Pereira N, Pitt W, Porter C, Prabhu S, Promisloff S, Ratkovec R, Richardson R, Ross A, Saleh N, Saltzberg M, Sarkar S, Schmedtje J, Schneider R, Schuyler G, Shanes J, Sharma A, Siegel C, Siegel R, Silber D, Singh N, Singh J, Singh V, Sklar J, Small R, Smith A, Smith E, Smull D, Sotolongo R, Staniloae C, Stapleton D, Steele P, Stehlik J, Stein M, Tang W, Thadani U, Torre Amoine G, Trichon B, Tsai C, Tummala R, Van Bakel A, Vicari R, Vijay N, Vijayaraghavan K, Vittorio T, Vossler M, Wagoner L, Wallis D, Ward N, Widmer M, Wight J, Wilkins C, Williams C, Williams G, Winchester M, Winkel E, Wittmer B, Wood D, Wormer D, Wright R, Xu Z, Yasin M, Zolty R., PERRONE FILARDI, PASQUALE, Karl, Swedberg, James B., Young, Inder S., Anand, Sunfa, Cheng, Akshay S., Desai, Rafael, Diaz, Aldo P., Maggioni, John J. V., Mcmurray, Christopher, O'Connor, Marc A., Pfeffer, Scott D., Solomon, Yan, Sun, Michal, Tendera, Dirk J., van Veldhuisen, Young, J, Grinfeld, L, Krum, H, Vanhaecke, J, Olivera Clausell, N, Goudev, A, Howlett, J, Corbalan, R, Hradec, J, Kober, L, Eha, J, Cohen Solal, A, Anker, Sd, Chopra, V, Lewis, B, Erglis, A, Sakalyte, G, Cardona Munoz, E, Dunselman, P, Dickstein, K, Ponikowski, P, Seabra Gomes, R, Apetrei, E, Mareev, V, Murin, J, Dalby, A, Lopez Sendon, J, Willenheimer, R, Cleland, J, Adams, K, Anand, I, Butler, J, Dunlap, M, Felker, M, Ghali, J, Levy, W, Carson, P, Cohn, J, Drexler, H, Pocock, S, Ryden, L, Poole Wilson, P, Fishbane, S, Ivanovich, P, Nissenson, A, Katz, S, Barkoudah, E, Campbell, P, Desai, A, Finn, Pv, Hartley, L, Kasabov, R, Odutayo, Ka, Rajesh, V, Solomon, S, Weinrauch, La, Albizem, M, Cheng, S, Chou, W, Deegenaars, M, Dougherty, M, Fouqueray, B, Froissart, M, Froment, A, Gadd, S, Ghosh, S, Grazette, L, Guillet, S, Gulabani, D, Haddock, B, Harris, C, Jaffer, A, Kerns, C, Kim, J, Knussel, B, Law, H, Mather, R, Mix, C, Moore, L, Moyes, R, Polu, K, Rossert, J, Scarlata, D, Smirnakis, K, Smith, L, Snyder, W, Sun, Y, Trotman, Ml, Wasserman, S, Watkins, A, Wong, M, Zhang, Y, Amuchastegui, M, Belziti, C, Bluguermann, J, Caccavo, M, Cartasegna, L, Colque, R, Cuneo, C, Fernandez, A, Gabito, A, Goicochea, R, Gonzalez, M, Gorosito, V, Hominal, M, Kevorkian, R, Litvak Bruno, M, Llanos, J, Mackinnon, I, Manuale, O, Marzetti, E, Nul, D, Perna, E, Riccitelli, M, Sanchez, A, Santos, D, Schygiel, P, Toblli, J, Vogel, D, Aggarwal, A, Amerena, J, De Looze, F, Fletcher, P, Hare, D, Ireland, M, Lattimore, J, Marwick, T, Sindone, A, Thompson, P, Waites, J, Altenberger, J, Ebner, C, Lenz, K, Pacher, R, Poelzl, G, Charlier, F, de Ceuninck, M, De Keulenaer, G, Dendale, P, Maréchal, P, Mullens, W, Thoeng, J, Vanderheyden, M, Weytjens, C, Wollaert, B, Albuquerque, D, Almeida, D, Aspe y., Rosas J, Bocchi, E, Bordignon, S, Clausell, N, Kaiser, S, Leaes, P, Martins Alves, S, Montera, M, Moura, L, Pereira de Castro, R, Rassi, S, Reis, A, Saraiva, J, Simões, M, Souza Neto, J, Teixeira, M, Benov, H, Chompalova, B, Donova, T, Georgiev, P, Gotchev, D, Grigorov, M, Guenova, D, Hergeldjieva, V, Ivanov, D, Kostova, E, Manolova, A, Marchev, S, Nikolov, F, Popov, A, Raev, D, Tzekova, M, Czarnecki, W, Giannetti, N, Haddad, H, Heath, J, Huynh, T, Lepage, S, Liu, P, Lonn, E, Ma, P, Manyari, D, Moe, G, Parker, J, Pesant, Y, Rajda, M, Ricci, J, Roth, S, Sestier, F, Sluzar, V, Sussex, B, Vizel, S, Antezana, G, Bugueno, C, Castro, P, Conejeros, C, Manriquez, L, Martinez, D, Potthoff, S, Stockins, B, Vukasovic, J, Gregor, P, Herold, M, Jerabek, O, Jirmar, R, Kuchar, R, Linhart, A, Podzemska, B, Soucek, M, Spac, J, Spacek, R, Vodnansky, P, Bronnum Schou, J, Clemmensen, K, Egstrup, K, Jensen, G, Kjoller Hansen, L, Markenvard, J, Rokkedal, J, Skagen, K, Torp Pedersen, C, Tuxen, C, Videbak, L, Laks, T, Vahula, V, Harjola, V, Kettunen, R, Kotila, M, Bauer, F, Coisne, D, Davy, J, De Groote, P, Dos Santos, P, Funck, F, Galinier, M, Gibelin, P, Isnard, R, Neuder, Y, Roul, G, Sabatier, R, Trochu, J, Denny, S, Dreykluft, T, Flesch, M, Genth Zotz, S, Hambrecht, R, Hein, J, Jeserich, M, John, M, Kreider Stempfle, H, Laufs, U, Muellerleile, K, Natour, M, Sandri, M, Schäufele, T, von Hodenberg, E, Weyland, K, Winkelmann, B, Tse, H, Yan, B, Barsi, B, Csikasz, J, Dezsi, C, Edes, I, Forster, T, Karpati, P, Kerekes, C, Kis, E, Kosa, I, Lupkovics, G, Nagy, A, Preda, I, Ronaszeki, A, Tomcsanyi, J, Zamolyi, K, Agarwal, D, Bahl, V, Bordoloi, A, Chockalingam, K, Chopda, M, Dugal, J, Ghaisas, N, Grant, P, Hiremath, S, Iyengar, S, Jagadeesa Subramania, B, Jain, P, Joshi, A, Khan, A, Mullasari, A, Naik, S, Oomman, A, Pai, V, Pareppally Gopal, R, Parikh, K, Patel, T, Prakash, V, Sastry, B, Sathe, S, Sinha, N, Srikanthan, V, Subburamakrishnan, P, Thacker, H, Wander, G, Admon, D, Katz, A, Klainman, E, Marmor, A, Moriel, M, Mosseri, M, Shotan, A, Weinstein, J, Zimlichman, R, Agostoni, P, Albanese, M, Alunni, G, Bini, R, Boccanelli, A, Bolognese, L, Campana, C, Carbonieri, E, Carpino, C, Checco, L, Cosmi, F, Angelo, Gd, De Cristofaro, M, Floresta, A, Fucili, A, Galvani, M, Ivleva, A, Marra, S, Musca, G, Peccerillo, N, PERRONE FILARDI, Pasquale, Picchio, E, Russo, T, Scelsi, L, Senni, M, Tavazzi, L, Jasinkevica, I, Kakurina, N, Veze, I, Volans, E, Bagdonas, A, Berukstis, E, Celutkiene, J, Dambrauskaite, A, Jarasuniene, D, Luksiene, D, Rudys, A, Sliaziene, S, Aguilar Romero, R, Cardona Muñoz, E, Castro Jimenez, J, Chavez Herrera, J, Chuquiure Valenzuela, E, De la Pena, G, Herrera, E, Leiva Pons, J, Lopez Alvarado, A, Mendez Machado, G, Ramos Lopez, G, Basart, D, Buijs, E, Cornel, J, de Leeuw, M, Dijkgraaf, R, Freericks, M, Hamraoui, K, Lenderlink, T, Linssen, G, Lodewick, P, Lodewijks, C, Lok, D, Nierop, P, Ronner, E, Somsen, A, van Dantzig, J, van der Burgh, P, van Kempen, L, van Vlies, B, Voors, A, Wardeh, A, Willems, F, Gundersen, T, Hole, T, Thalamus, J, Westheim, A, Dabrowski, M, Gorski, J, Korewicki, J, Kuc, K, Miekus, P, Musial, W, Niegowska, J, Piotrowski, W, Podolec, P, Polonski, L, Rynkiewicz, A, Szelemej, R, Trusz Gluza, M, Ujda, M, Wojciechowski, D, Wysokinski, A, Camacho, A, Fonseca, C, Monteiro, P, Bruckner, I, Carasca, E, Coman, I, Datcu, M, Dragulescu, S, Ionescu, P, Iordachescu Petica, D, Manitiu, I, Popa, V, Pop Moldovan, A, Radoi, M, Stamate, S, Tomescu, M, Vita, I, Aroutiounov, G, Ballyuzek, M, Bart, B, Churina, S, Glezer, M, Goloshchekin, B, Kobalava, Z, Kostenko, V, Lopatin, Y, Martynov, A, Orlov, V, Semernin, E, Shogenov, Z, Sidorenko, B, Skvortsov, A, Storzhakov, G, Sulimov, V, Talibov, O, Tereshenko, S, Tsyrline, V, Zadionchenko, V, Zateyshchikov, D, Dzupina, A, Hranai, M, Kmec, J, Micko, K, Pella, D, Sojka, G, Spisak, V, Vahala, P, Vinanska, D, Badat, A, Bayat, J, Dawood, S, Delport, E, Ellis, G, Garda, R, Klug, E, Mabin, T, Naidoo, D, Pretorius, M, Ranjith, N, Van Zyl, L, Weich, H, Anguita, M, Berrazueta, J, Bruguera i., Cortada J, de Teresa, E, Gómez Sánchez, M, González Juanatey, J, Gonzalez Maqueda, I, Jordana, R, Lupon, J, Manzano, L, Pascual Figal, D, Pulpón, L, Recio, J, Ridocci Soriano, F, Rodríguez Lambert, J, Roig Minguell, E, Romero, J, Valdovinos, P, Klintberg, L, Kronvall, T, Lycksell, M, Morner, S, Rydberg, E, Swedberg, K, Timberg, I, Wikstrom, G, Moccetti, T, Ashok, J, Banerjee, P, Carr White, G, Connolly, E, Francis, M, Greenbaum, R, Kadr, H, Lindsay, S, Mcmurray, J, Megarry, S, Memon, A, Murdoch, D, Senior, R, Squire, I, Tan, L, Witte, K, Adamson, P, Adler, A, Altschul, L, Altschuller, A, Amirani, H, Andreou, C, Ansari, M, Antonishen, M, Banchs, H, Banerjee, S, Banish, D, Bank, A, Barbagelata, A, Barnard, D, Bellinger, R, Benn, A, Berk, M, Berry, B, Bethala, V, Bilazarian, S, Bisognano, J, Bleyer, F, Blum, M, Boehmer, J, Bouchard, A, Boyle, A, Bozkurt, B, Brown, C, Burlew, B, Burnham, K, Call, J, Cambier, P, Cappola, T, Carlson, R, Chandler, B, Chandra, R, Chandraratna, P, Chernick, R, Colan, D, Colfer, H, Colucci, W, Connelly, T, Costantini, O, Dadkhah, S, Dauber, I, Davis, J, Davis, S, Denning, S, Drazner, M, Dunlap, S, Egbujiobi, L, Elkayam, U, Elliott, J, El Shahawy, M, Essandoh, L, Ewald, G, Fang, J, Farhoud, H, Felker, G, Fernandez, J, Festin, R, Fishbein, G, Florea, V, Flores, E, Floro, J, Gabris, M, Garg, M, Gatewood, R, Geller, M, Ghumman, W, Gibbs, G, Gillespie, E, Gilmore, R, Gogia, H, Goldberg, L, Gradus Pizlo, I, Grainger, T, Gudmundsson, G, Gunawardena, D, Gupta, D, Hack, T, Hall, S, Hamroff, G, Hankins, S, Hanna, M, Hargrove, J, Haught, W, Hauptman, P, Hazelrigg, M, Herzog, C, Heywood, J, Hill, T, Hilton, T, Hirsch, H, Hunter, J, Ibrahim, H, Imburgia, M, Iteld, B, Jackson, B, Jaffrani, N, Jain, D, Jain, A, James, M, Jimenez, J, Johnson, E, Kale, P, Kaneshige, A, Kapadia, S, Karia, D, Karlsberg, R, Katholi, R, Kerut, E, Khoury, W, Kipperman, R, Klapholz, M, Kosinski, E, Kozinn, M, Kraus, D, Krueger, S, Kumar, S, Lader, E, Lee, C, Lewis, E, Light McGroary, K, Loh, I, Lombardi, W, Machado, C, Maislos, F, Mancini, D, Markus, T, Mather, P, Mccants, K, Mcgrew, F, Mclaurin, B, Mcmillan, E, Mcnamara, D, Meyer, T, Meymandi, S, Miller, A, Minami, E, Modi, M, Mody, F, Mohanty, P, Moscoso, R, Moskowitz, R, Moustafa, M, Mullen, M, Naz, T, Noonan, T, O., Brien T, Oellerich, W, Oren, R, Pamboukian, S, Pereira, N, Pitt, W, Porter, C, Prabhu, S, Promisloff, S, Ratkovec, R, Richardson, R, Ross, A, Saleh, N, Saltzberg, M, Sarkar, S, Schmedtje, J, Schneider, R, Schuyler, G, Shanes, J, Sharma, A, Siegel, C, Siegel, R, Silber, D, Singh, N, Singh, J, Singh, V, Sklar, J, Small, R, Smith, A, Smith, E, Smull, D, Sotolongo, R, Staniloae, C, Stapleton, D, Steele, P, Stehlik, J, Stein, M, Tang, W, Thadani, U, Torre Amoine, G, Trichon, B, Tsai, C, Tummala, R, Van Bakel, A, Vicari, R, Vijay, N, Vijayaraghavan, K, Vittorio, T, Vossler, M, Wagoner, L, Wallis, D, Ward, N, Widmer, M, Wight, J, Wilkins, C, Williams, C, Williams, G, Winchester, M, Winkel, E, Wittmer, B, Wood, D, Wormer, D, Wright, R, Xu, Z, Yasin, M, Zolty, R., Faculteit Medische Wetenschappen/UMCG, and Cardiovascular Centre (CVC)
Subjects: Male, CHRONIC KIDNEY-DISEASE, Darbepoetin alfa, Ciencias de la Salud, Kaplan-Meier Estimate, law.invention, Hemoglobins, DOUBLE-BLIND, Randomized controlled trial, law, hemic and lymphatic diseases, Treatment Failure, Hazard ratio, Ética Médica, Anemia, General Medicine, Middle Aged, Shock, Septic, Stroke, purl.org/becyt/ford/3 [https], Female, medicine.drug, medicine.medical_specialty, CIENCIAS MÉDICAS Y DE LA SALUD, Placebo, CONTROLLED-TRIAL, purl.org/becyt/ford/3.3 [https], MORBIDITY, Double-Blind Method, Darbepoetin, Internal medicine, Thromboembolism, parasitic diseases, medicine, Humans, Adverse effect, Erythropoietin, Aged, Proportional Hazards Models, CITY CARDIOMYOPATHY QUESTIONNAIRE, business.industry, Proportional hazards model, MORTALITY, equipment and supplies, medicine.disease, Surgery, REDUCTION, EPOETIN, Heart failure, Hematinics, business, Systolic heart failure, Heart Failure, Systolic
Abstract: BACKGROUND: Patients with systolic heart failure and anemia have worse symptoms, functional capacity, and outcomes than those without anemia. We evaluated the effects of darbepoetin alfa on clinical outcomes in patients with systolic heart failure and anemia. METHODS: In this randomized, double-blind trial, we assigned 2278 patients with systolic heart failure and mild-to-moderate anemia (hemoglobin level, 9.0 to 12.0 g per deciliter) to receive either darbepoetin alfa (to achieve a hemoglobin target of 13 g per deciliter) or placebo. The primary outcome was a composite of death from any cause or hospitalization for worsening heart failure. RESULTS: The primary outcome occurred in 576 of 1136 patients (50.7%) in the darbepoetin alfa group and 565 of 1142 patients (49.5%) in the placebo group (hazard ratio in the darbepoetin alfa group, 1.01; 95% confidence interval, 0.90 to 1.13; P=0.87). There was no significant between-group difference in any of the secondary outcomes. The neutral effect of darbepoetin alfa was consistent across all prespecified subgroups. Fatal or nonfatal stroke occurred in 42 patients (3.7%) in the darbepoetin alfa group and 31 patients (2.7%) in the placebo group (P=0.23). Thromboembolic adverse events were reported in 153 patients (13.5%) in the darbepoetin alfa group and 114 patients (10.0%) in the placebo group (P=0.01). Cancer-related adverse events were similar in the two study groups. CONCLUSIONS: Treatment with darbepoetin alfa did not improve clinical outcomes in patients with systolic heart failure and mild-to-moderate anemia. Our findings do not support the use of darbepoetin alfa in these patients. (Funded by Amgen; RED-HF ClinicalTrials.gov number, NCT00358215.). Fil: Swedberg, Karl. University of Gothenburg; Suecia Fil: Young, James B.. Cleveland Clinic; Estados Unidos Fil: Anand, Inder S.. University of Minnesota; Estados Unidos Fil: Cheng, Sunfa. Amgen; Estados Unidos Fil: Desai, Akshay S.. Brigham and Women’s Hospital; Estados Unidos Fil: Diaz, Rafael. Estudios Clínicos Latinoamérica; Argentina Fil: Maggioni, Aldo P.. Italian Association of Hospital Cardiologists Research Center; Italia Fil: McMurray, John J.V.. University of Glasgow; Reino Unido Fil: O’Connor, Christopher. University of Duke; Estados Unidos Fil: Pfeffer, Marc A.. Brigham and Women’s Hospital; Estados Unidos Fil: Solomon, Scott D.. Brigham and Women’s Hospital; Estados Unidos Fil: Sun, Yan. Amgen; Estados Unidos Fil: Tendera, Michal. Medical University of Silesia; Polonia Fil: van Veldhuisen, Dirk J.. University of Groningen; Países Bajos Fil: Toblli, Jorge Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Published: 2013

4. CYP3A4 genotype is associated with sildenafil concentrations in patients with heart failure with preserved ejection fraction

Author: de Denus, S, primary, Rouleau, J L, additional, Mann, D L, additional, Huggins, G S, additional, Pereira, N L, additional, Shah, S H, additional, Cappola, T P, additional, Fouodjio, R, additional, Mongrain, I, additional, and Dubé, M-P, additional
Published: 2017
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5. Shared genetic etiology of peripartum and dilated cardiomyopathies

Author: Ware, JS, Li, J, Mazaika, E, Yasso, C, DeSouza, T, Cappola, T, Tsai, EJ, Hilfiker Kleiner, D, Kamiya, CA, Mazzarotto, F, Cook, SA, Halder, I, Prasad, SK, Pisarcik, J, Hanley Yanez, K, Alharethi, R, Damp, J, Hsich, E, Elkayam, U, Sheppard, R, Kealey, A, Alexis, J, Ramani, G, Safirstein, J, Boehmer, J, Pauly, DF, Wittstein, IS, Thohan, V, Zucker, MJ, Liu, P, Gorcsan, J, McNamara, DM, Seidman, CE, Seidman, JG, Arany, Z, Commission of the European Communities, and British Heart Foundation
Subjects: Adult, Cardiomyopathy, Dilated, OUTCOMES, Science & Technology, MUTATIONS, Pregnancy Complications, Cardiovascular, Stroke Volume, Sequence Analysis, DNA, IMAC-2 and IPAC Investigators, GENOME, Medicine, General & Internal, Pregnancy, General & Internal Medicine, Case-Control Studies, Mutation, Peripartum Period, Humans, Protein Isoforms, FAMILIAL OCCURRENCE, Connectin, Female, Genetic Predisposition to Disease, Cardiomyopathies, Life Sciences & Biomedicine, 11 Medical and Health Sciences
Abstract: Background: Peripartum cardiomyopathy (PPCM) shares some clinical features with idiopathic dilated cardiomyopathy, a disorder caused by mutations in over 40 genes, including TTN, which encodes the sarcomere protein titin. Methods: We sequenced 43 genes, with variants that have been associated with dilated cardiomyopathy, in 172 women with peripartum cardiomyopathy. We compared the prevalence of different types of variant (nonsense, frameshift, and splicing) in these women with the prevalence of these variants in persons with dilated cardiomyopathy and population controls. Results: We identified 26 distinct rare truncating variants in eight genes in women with PPCM. The prevalence of truncating variants (26 in 172 [15%]) was significantly higher than in a reference population of 60,706 individuals (4.7%, P=1.3x10-7), but was similar to a cohort of 332 dilated cardiomyopathy cases (55 in 332 [17%], P=0.81). Two thirds of identified truncating variants were in TTN ([10%], P=2.7x10-10 versus 1.4% in reference population), almost all located in the titin A-band. Seven of the TTN truncating variants were previously reported in cases of idiopathic dilated cardiomyopathy. In a clinically well-characterized cohort of women with PPCM (n=83), the presence of TTN truncating variants correlated with lower ejection fraction at one-year follow-up (P=0.005). Conclusions: The distribution of truncating variants in a large series of women with PPCM is remarkably similar to that found in idiopathic dilated cardiomyopathy. TTN truncating variants are the most prevalent genetic predisposition of each disorder.
Published: 2015

6. A pharmacogenetic investigation of intravenous furosemide in decompensated heart failure: a meta-analysis of three clinical trials

Author: de Denus, S, primary, Rouleau, J L, additional, Mann, D L, additional, Huggins, G S, additional, Cappola, T P, additional, Shah, S H, additional, Keleti, J, additional, Zada, Y F, additional, Provost, S, additional, Bardhadi, A, additional, Phillips, M S, additional, Normand, V, additional, Mongrain, I, additional, and Dubé, M-P, additional
Published: 2016
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7. Gene-centric meta-analyses of 108 912 individuals confirm known body mass index loci and reveal three novel signals

Author: Guo, Y., Lanktree, M. B., Taylor, K. C., Hakonarson, H., Lange, L. A., Keating, B. J., Fairfax, B. P., Elbers, C. C., Barnard, J., Farrall, M., Padmanabhan, S., Baumert, J., Castillo, B. A., Gaunt, T. R., Gong, Y., Rajagopalan, R., Romaine, S. P., Kumari, M., Rafelt, S., Smith, E. N., Li, Y. R., Sivapalaratnam, S., van Iperen, E. P., Speliotes, E. K., Toskala, E., Zhang, L., Ochs-Balcom, H. M., Bhangale, T. R., Chandrupatla, H. R., Drenos, F., Gieger, C., Gupta, J., Johnson, T., Kleber, M. E., Makino, S., Mangino, M., Meng, Y., Nelson, C. P., Pankow, J. S., Pankratz, N., Price, T. S., Shaffer, J., Shen, H., Tischfield, S., Tomaszewski, M., Atwood, L. D., Bailey, K. M., Balasubramanyam, A., Baldwin, C. T., Basart, H., Bauer, F., Behr, E. R., Beitelshees, A. L., Berenson, G. S., Beresford, S. A., Bezzina, C. R., Bhatt, D. L., Boer, J. M., Braund, P. S., Burke, G. L., Burkley, B., Carty, C., Chen, W., Clarke, R., Cooper-DeHoff, R. M., Curtis, S. P., de Bakker, P. I., de Jong, J. S., Delles, C., Dominiczak, A. F., Duggan, D., Feldman, H. I., Furlong, C. E., Gorski, M. M., Gums, J. G., Hardwick, R., Hastie, C., Heid, I. M., Huang, G.-H., Huggins, G. S., Humphries, S. E., Kirkland, S. A., Kivimaki, M., Klein, R., Klein, B. E., Knowler, W. C., Kottke-Marchant, K., LaCroix, A. Z., Langaee, T. Y., Li, M., Lyon, H. N., Maiwald, S., Marshall, J. K., Mehta, A., Meijs, M. F., Melander, O., Meyer, N., Mitra, N., Molony, C. M., Morrow, D. A., Murugesan, G., Newhouse, S. J., Nieto, J. F., Onland-Moret, N. C., Ouwehand, W. H., Palmen, J., Pepine, C. J., Ranchalis, J., Rosas, S. E., Rosenthal, E. A., Scharnagl, H., Schork, N. J., Schreiner, P. J., Shah, T., Shashaty, M., Shimbo, D., Srinivasan, S. R., Thomas, F., Tobin, M. D., Tsai, M. Y., Verschuren, W. M. M., Wagenknecht, L. E., Winkelmann, B. R., Young, T., Yusuf, S., Zafarmand, M. H., Zmuda, J. M., Zwinderman, A. H., Anand, S. S., Balmforth, A. J., Boehm, B. O., Boerwinkle, E., Burton, P. R., Cappola, T. P., Casas, J. P., Caulfield, M. J., Christiani, D. C., Christie, J., Cruickshanks, K. J., Davey-Smith, G., Davidson, K. W., Day, I. N., Doevendans, P. A., Dorn, G. W., FitzGerald, G. A., Hall, A. S., Hingorani, A. D., Hirschhorn, J. N., Hofker, M. H., Hovingh, K. G., Illig, T., Jamshidi, Y., Jarvik, G. P., Johnson, J. A., Kanetsky, P. A., Kastelein, J. J., Koenig, W., Lawlor, D. A., Marz, W., McCaffery, J., Mega, J. L., Mitchell, B. D., Murray, S. S., O'Connell, J. R., Patel, S. R., Peters, A., Pettinger, M., Rader, D. J., Redline, S., Reilly, M. P., Sabatine, M. S., Schadt, E. E., Shuldiner, A. R., Silverstein, R. L., Spector, T. D., Taylor, H. A., Thorand, B., Trip, M. D., Watkins, H., Wichmann, H.- E., Fox, C. S., Grant, S. F., Peter, I., Talmud, P. J., Munroe, P. B., Wilson, J. G., Knight, J. C., Samani, N. J., Hegele, R. A., Asselbergs, F. W., Monda, K. L., van der Schouw, Y. T., Demerath, E. W., Wijmenga, C., Timpson, N. J., Reiner, A. P., North, K. E., Papanicolaou, G. J., Lange , L. A., Keating , B. J., Vascular Medicine, Amsterdam Public Health, Epidemiology and Data Science, Graduate School, Other departments, Amsterdam Cardiovascular Sciences, Cardiology, Other Research, and Public and occupational health
Subjects: Population, Single-nucleotide polymorphism, Genome-wide association study, Biology, Polymorphism, Single Nucleotide, Body Mass Index, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, SH2B1, Genotype, Ethnicity, Genetics, Humans, education, Molecular Biology, Gene, Genetics (clinical), 030304 developmental biology, Genetic association, 0303 health sciences, education.field_of_study, Association Studies Articles, General Medicine, Melanocortin 4 receptor, 030217 neurology & neurosurgery
Abstract: Recent genetic association studies have made progress in uncovering components of the genetic architecture of the body mass index (BMI). We used the ITMAT-Broad-Candidate Gene Association Resource (CARe) (IBC) array comprising up to 49 320 single nucleotide polymorphisms (SNPs) across ~2100 metabolic and cardiovascular-related loci to genotype up to 108 912 individuals of European ancestry (EA), African-Americans, Hispanics and East Asians, from 46 studies, to provide additional insight into SNPs underpinning BMI. We used a five-phase study design: Phase I focused on meta-analysis of EA studies providing individual level genotype data; Phase II performed a replication of cohorts providing summary level EA data; Phase III meta-analyzed results from the first two phases; associated SNPs from Phase III were used for replication in Phase IV; finally in Phase V, a multi-ethnic meta-analysis of all samples from four ethnicities was performed. At an array-wide significance (P < 2.40E-06), we identify novel BMI associations in loci translocase of outer mitochondrial membrane 40 homolog (yeast) - apolipoprotein E - apolipoprotein C-I (TOMM40-APOE-APOC1) (rs2075650, P = 2.95E-10), sterol regulatory element binding transcription factor 2 (SREBF2, rs5996074, P = 9.43E-07) and neurotrophic tyrosine kinase, receptor, type 2 [NTRK2, a brain-derived neurotrophic factor (BDNF) receptor gene, rs1211166, P = 1.04E-06] in the Phase IV meta-analysis. Of 10 loci with previous evidence for BMI association represented on the IBC array, eight were replicated, with the remaining two showing nominal significance. Conditional analyses revealed two independent BMI-associated signals in BDNF and melanocortin 4 receptor (MC4R) regions. Of the 11 array-wide significant SNPs, three are associated with gene expression levels in both primary B-cells and monocytes; with rs4788099 in SH2B adaptor protein 1 (SH2B1) notably being associated with the expression of multiple genes in cis. These multi-ethnic meta-analyses expand our knowledge of BMI genetics.
Published: 2013

8. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

Author: Arking, D, Pulit, S, Crotti, L, van der Harst, P, Munroe, P, Koopmann, T, Sotoodehnia, N, Rossin, E, Morley, M, Wang, X, Johnson, A, Lundby, A, Gudbjartsson, D, Noseworthy, P, Eijgelsheim, M, Bradford, Y, Tarasov, K, Dörr, M, Müller-Nurasyid, M, Lahtinen, A, Nolte, I, Smith, A, Bis, J, Isaacs, A, Newhouse, S, Evans, D, Post, W, Waggott, D, Lyytikäinen, L, Hicks, A, Eisele, L, Ellinghaus, D, Hayward, C, Navarro, P, Ulivi, S, Tanaka, T, Tester, D, Chatel, S, Gustafsson, S, Kumari, M, Morris, R, Naluai, A, Padmanabhan, S, Kluttig, A, Strohmer, B, Panayiotou, A, Torres, M, Knoflach, M, Hubacek, J, Slowikowski, K, Raychaudhuri, S, Kumar, R, Harris, T, Launer, L, Shuldiner, A, Alonso, A, Bader, J, Ehret, G, Huang, H, Kao, W, Strait, J, Macfarlane, P, Brown, M, Caulfield, M, Samani, N, Kronenberg, F, Willeit, J, Smith, J, Greiser, K, Meyer Zu Schwabedissen, H, Werdan, K, Carella, M, Zelante, L, Heckbert, S, Psaty, B, Rotter, J, Kolcic, I, Polašek, O, Wright, A, Griffin, M, Daly, M, Arnar, D, Hólm, H, Thorsteinsdottir, U, Denny, J, Roden, D, Zuvich, R, Emilsson, V, Plump, A, Larson, M, O'Donnell, C, Yin, X, Bobbo, M, D'Adamo, A, Iorio, A, Sinagra, G, Carracedo, A, Cummings, S, Nalls, M, Jula, A, Kontula, K, Marjamaa, A, Oikarinen, L, Perola, M, Porthan, K, Erbel, R, Hoffmann, P, Jöckel, K, Kälsch, H, Nöthen, M, den Hoed, M, Loos, R, Thelle, D, Gieger, C, Meitinger, T, Perz, S, Peters, A, Prucha, H, Sinner, M, Waldenberger, M, de Boer, R, Franke, L, van der Vleuten, P, Beckmann, B, Martens, E, Bardai, A, Hofman, N, Wilde, A, Behr, E, Dalageorgou, C, Giudicessi, J, Medeiros-Domingo, A, Kyndt, F, Probst, V, Ghidoni, A, Insolia, R, Hamilton, R, Scherer, S, Brandimarto, J, Margulies, K, Moravec, C, Greco, M, Fuchsberger, C, O'Connell, J, Lee, W, Watt, G, Campbell, H, Wild, S, El Mokhtari, N, Frey, N, Asselbergs, F, Mateo Leach, I, Navis, G, van den Berg, M, van Veldhuisen, D, Kellis, M, Krijthe, B, Franco, O, Hofman, A, Kors, J, Uitterlinden, A, Witteman, J, Kedenko, L, Lamina, C, Oostra, B, Abecasis, G, Lakatta, E, Mulas, A, Orrú, M, Schlessinger, D, Uda, M, Markus, M, Völker, U, Snieder, H, Spector, T, Arnlöv, J, Lind, L, Sundström, J, Syvänen, A, Kivimaki, M, Kähönen, M, Mononen, N, Raitakari, O, Viikari, J, Adamkova, V, Kiechl, S, Brion, M, Nicolaides, A, Paulweber, B, Haerting, J, Dominiczak, A, Nyberg, F, Whincup, P, Hingorani, A, Schott, J, Bezzina, C, Ingelsson, E, Ferrucci, L, Gasparini, P, Wilson, J, Rudan, I, Franke, A, Mühleisen, T, Pramstaller, P, Lehtimäki, T, Paterson, A, Parsa, A, Liu, Y, van Duijn, C, Siscovick, D, Gudnason, V, Jamshidi, Y, Salomaa, V, Felix, S, Sanna, S, Ritchie, M, Stricker, B, Stefansson, K, Boyer, L, Cappola, T, Olsen, J, Lage, K, Schwartz, P, Kääb, S, Chakravarti, A, Ackerman, M, Pfeufer, A, de Bakker, P, Newton-Cheh, C, Arking, DE, Pulit, SL, Munroe, PB, Rossin, EJ, Johnson, AD, Gudbjartsson, DF, Noseworthy, PA, Tarasov, KV, Lahtinen, AM, Nolte, IM, Smith, AV, Bis, JC, Newhouse, SJ, Evans, DS, Post, WS, Lyytikäinen, LP, Hicks, AA, Tester, DJ, Morris, RW, Naluai, AT, Panayiotou, AG, Hubacek, JA, Kumar, RD, Harris, TB, Launer, LJ, Shuldiner, AR, Bader, JS, Kao, WH, Strait, JB, Macfarlane, PW, Caulfield, MJ, Samani, NJ, Smith, JG, Greiser, KH, Heckbert, SR, Psaty, BM, Rotter, JI, Wright, AF, Daly, MJ, Arnar, DO, Denny, JC, Roden, DM, Zuvich, RL, Plump, AS, Larson, MG, O'Donnell, CJ, D'Adamo, AP, Cummings, SR, Nalls, MA, Kontula, KK, Jöckel, KH, Nöthen, MM, Loos, RJ, Thelle, DS, Sinner, MF, de Boer, RA, van der Vleuten, PA, Beckmann, BM, Wilde, AA, Behr, ER, Giudicessi, JR, Hamilton, RM, Scherer, SW, Moravec, CE, Greco, MFD, O'Connell, JR, Lee, WK, Watt, GC, Wild, SH, El Mokhtari, NE, Asselbergs, FW, van den Berg, MP, van Veldhuisen, DJ, Krijthe, BP, Franco, OH, Kors, JA, Uitterlinden, AG, Witteman, JC, Oostra, BA, Abecasis, GR, Lakatta, EG, Markus, MR, Spector, TD, Syvänen, AC, Raitakari, OT, Viikari, JS, Nicolaides, AN, Dominiczak, AF, Whincup, PH, Hingorani, AD, Schott, JJ, Bezzina, CR, Wilson, JF, Mühleisen, TW, Pramstaller, PP, Lehtimäki, TJ, Paterson, AD, van Duijn, CM, Siscovick, DS, Felix, SB, Ritchie, MD, Stricker, BH, Boyer, LA, Cappola, TP, Olsen, JV, Schwartz, PJ, Ackerman, MJ, de Bakker, PI, Arking, D, Pulit, S, Crotti, L, van der Harst, P, Munroe, P, Koopmann, T, Sotoodehnia, N, Rossin, E, Morley, M, Wang, X, Johnson, A, Lundby, A, Gudbjartsson, D, Noseworthy, P, Eijgelsheim, M, Bradford, Y, Tarasov, K, Dörr, M, Müller-Nurasyid, M, Lahtinen, A, Nolte, I, Smith, A, Bis, J, Isaacs, A, Newhouse, S, Evans, D, Post, W, Waggott, D, Lyytikäinen, L, Hicks, A, Eisele, L, Ellinghaus, D, Hayward, C, Navarro, P, Ulivi, S, Tanaka, T, Tester, D, Chatel, S, Gustafsson, S, Kumari, M, Morris, R, Naluai, A, Padmanabhan, S, Kluttig, A, Strohmer, B, Panayiotou, A, Torres, M, Knoflach, M, Hubacek, J, Slowikowski, K, Raychaudhuri, S, Kumar, R, Harris, T, Launer, L, Shuldiner, A, Alonso, A, Bader, J, Ehret, G, Huang, H, Kao, W, Strait, J, Macfarlane, P, Brown, M, Caulfield, M, Samani, N, Kronenberg, F, Willeit, J, Smith, J, Greiser, K, Meyer Zu Schwabedissen, H, Werdan, K, Carella, M, Zelante, L, Heckbert, S, Psaty, B, Rotter, J, Kolcic, I, Polašek, O, Wright, A, Griffin, M, Daly, M, Arnar, D, Hólm, H, Thorsteinsdottir, U, Denny, J, Roden, D, Zuvich, R, Emilsson, V, Plump, A, Larson, M, O'Donnell, C, Yin, X, Bobbo, M, D'Adamo, A, Iorio, A, Sinagra, G, Carracedo, A, Cummings, S, Nalls, M, Jula, A, Kontula, K, Marjamaa, A, Oikarinen, L, Perola, M, Porthan, K, Erbel, R, Hoffmann, P, Jöckel, K, Kälsch, H, Nöthen, M, den Hoed, M, Loos, R, Thelle, D, Gieger, C, Meitinger, T, Perz, S, Peters, A, Prucha, H, Sinner, M, Waldenberger, M, de Boer, R, Franke, L, van der Vleuten, P, Beckmann, B, Martens, E, Bardai, A, Hofman, N, Wilde, A, Behr, E, Dalageorgou, C, Giudicessi, J, Medeiros-Domingo, A, Kyndt, F, Probst, V, Ghidoni, A, Insolia, R, Hamilton, R, Scherer, S, Brandimarto, J, Margulies, K, Moravec, C, Greco, M, Fuchsberger, C, O'Connell, J, Lee, W, Watt, G, Campbell, H, Wild, S, El Mokhtari, N, Frey, N, Asselbergs, F, Mateo Leach, I, Navis, G, van den Berg, M, van Veldhuisen, D, Kellis, M, Krijthe, B, Franco, O, Hofman, A, Kors, J, Uitterlinden, A, Witteman, J, Kedenko, L, Lamina, C, Oostra, B, Abecasis, G, Lakatta, E, Mulas, A, Orrú, M, Schlessinger, D, Uda, M, Markus, M, Völker, U, Snieder, H, Spector, T, Arnlöv, J, Lind, L, Sundström, J, Syvänen, A, Kivimaki, M, Kähönen, M, Mononen, N, Raitakari, O, Viikari, J, Adamkova, V, Kiechl, S, Brion, M, Nicolaides, A, Paulweber, B, Haerting, J, Dominiczak, A, Nyberg, F, Whincup, P, Hingorani, A, Schott, J, Bezzina, C, Ingelsson, E, Ferrucci, L, Gasparini, P, Wilson, J, Rudan, I, Franke, A, Mühleisen, T, Pramstaller, P, Lehtimäki, T, Paterson, A, Parsa, A, Liu, Y, van Duijn, C, Siscovick, D, Gudnason, V, Jamshidi, Y, Salomaa, V, Felix, S, Sanna, S, Ritchie, M, Stricker, B, Stefansson, K, Boyer, L, Cappola, T, Olsen, J, Lage, K, Schwartz, P, Kääb, S, Chakravarti, A, Ackerman, M, Pfeufer, A, de Bakker, P, Newton-Cheh, C, Arking, DE, Pulit, SL, Munroe, PB, Rossin, EJ, Johnson, AD, Gudbjartsson, DF, Noseworthy, PA, Tarasov, KV, Lahtinen, AM, Nolte, IM, Smith, AV, Bis, JC, Newhouse, SJ, Evans, DS, Post, WS, Lyytikäinen, LP, Hicks, AA, Tester, DJ, Morris, RW, Naluai, AT, Panayiotou, AG, Hubacek, JA, Kumar, RD, Harris, TB, Launer, LJ, Shuldiner, AR, Bader, JS, Kao, WH, Strait, JB, Macfarlane, PW, Caulfield, MJ, Samani, NJ, Smith, JG, Greiser, KH, Heckbert, SR, Psaty, BM, Rotter, JI, Wright, AF, Daly, MJ, Arnar, DO, Denny, JC, Roden, DM, Zuvich, RL, Plump, AS, Larson, MG, O'Donnell, CJ, D'Adamo, AP, Cummings, SR, Nalls, MA, Kontula, KK, Jöckel, KH, Nöthen, MM, Loos, RJ, Thelle, DS, Sinner, MF, de Boer, RA, van der Vleuten, PA, Beckmann, BM, Wilde, AA, Behr, ER, Giudicessi, JR, Hamilton, RM, Scherer, SW, Moravec, CE, Greco, MFD, O'Connell, JR, Lee, WK, Watt, GC, Wild, SH, El Mokhtari, NE, Asselbergs, FW, van den Berg, MP, van Veldhuisen, DJ, Krijthe, BP, Franco, OH, Kors, JA, Uitterlinden, AG, Witteman, JC, Oostra, BA, Abecasis, GR, Lakatta, EG, Markus, MR, Spector, TD, Syvänen, AC, Raitakari, OT, Viikari, JS, Nicolaides, AN, Dominiczak, AF, Whincup, PH, Hingorani, AD, Schott, JJ, Bezzina, CR, Wilson, JF, Mühleisen, TW, Pramstaller, PP, Lehtimäki, TJ, Paterson, AD, van Duijn, CM, Siscovick, DS, Felix, SB, Ritchie, MD, Stricker, BH, Boyer, LA, Cappola, TP, Olsen, JV, Schwartz, PJ, Ackerman, MJ, and de Bakker, PI
Abstract: The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD
Published: 2014

9. CYP3A4 genotype is associated with sildenafil concentrations in patients with heart failure with preserved ejection fraction

Author: de Denus, S, Rouleau, J L, Mann, D L, Huggins, G S, Pereira, N L, Shah, S H, Cappola, T P, Fouodjio, R, Mongrain, I, and Dubé, M-P
Abstract: Despite its established inter-individual variability, sildenafil has been the subject of only a few pharmacogenetic investigations, with limited data regarding the genetic modulators of its pharmacokinetics. We conducted a pharmacogenetic sub-study of patients randomized to sildenafil (n=85) in the RELAX trial, which investigated the impact of high-dose sildenafil in patients with heart failure with preserved left ventricular ejection fraction (HFpEF). In the overall population, the CYP3A4 inferred phenotype appeared associated with the dose-adjusted peak concentrations of sildenafil at week 12 and week 24 (adjusted P=0.045 for repeated measures analysis), although this P-value did not meet our corrected significance threshold of 0.0167. In the more homogeneous Caucasian subgroup, this association was significant (adjusted P=0.0165 for repeated measures). Hence, CYP3A4 inferred phenotype is associated with peak sildenafil dose-adjusted concentrations in patients with HFpEF receiving high doses of sildenafil. The clinical impact of this association requires further investigation.
Published: 2018
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10. Risk Prediction in Chronic Heart Failure

Author: Rizzo, T., primary and Cappola, T. P., additional
Published: 2012
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11. Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID): a phase 2 trial of intracoronary gene therapy of sarcoplasmic reticulum Ca2+-ATPase in patients with advanced heart failure.

Author: Jessup M, Greenberg B, Mancini D, Cappola T, Pauly DF, Jaski B, Yaroshinsky A, Zsebo KM, Dittrich H, Hajjar RJ, Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID) Investigators, Jessup, Mariell, Greenberg, Barry, Mancini, Donna, Cappola, Thomas, Pauly, Daniel F, Jaski, Brian, Yaroshinsky, Alex, Zsebo, Krisztina M, and Dittrich, Howard
Published: 2011
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12. Allopurinol improves myocardial efficiency in patients with idiopathic dilated cardiomyopathy.

Author: Cappola, T P, Kass, D A, Nelson, G S, Berger, R D, Rosas, G O, Kobeissi, Z A, Marbán, E, and Hare, J M
Published: 2001

13. Shared Genetic Predisposition in Peripartum and Dilated Cardiomyopathies.

Author: Ware, J. S., Li, J., Mazaika, E., Yasso, C. M., DeSouza, T., Cappola, T. P., Tsai, E. J., Hilfiker-Kleiner, D., Kamiya, C. A., Mazzarotto, F., Cook, S. A., Halder, I., Prasad, S. K., Pisarcik, J., Hanley-Yanez, K., Alharethi, R., Damp, J., Hsich, E., Elkayam, U., and Sheppard, R.
Published: 2016
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14. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

Author: Yuki Bradford, Toshiko Tanaka, Jeffrey R. O'Connell, Florence Kyndt, Unnur Thorsteinsdottir, Ivana Kolcic, Xiaoyan Yin, Vincent Probst, Manolis Kellis, Christopher Newton-Cheh, Stefan Kääb, Argelia Medeiros-Domingo, Markus M. Nöthen, Paolo Gasparini, Jean-Jacques Schott, Ruth J. F. Loos, Thomas W. Mühleisen, Annukka Marjamaa, Morris Brown, Igor Rudan, Runjun D. Kumar, Peter J. Schwartz, Lars Lind, Martina Müller-Nurasyid, Xinchen Wang, Joshua C. Denny, Roberto Insolia, Soumya Raychaudhuri, Stephen W. Scherer, Bruno H. Stricker, Alexander Kluttig, Adamo Pio D'Adamo, Laurie A. Boyer, Moritz F. Sinner, Norbert Frey, Nour Eddine El Mokhtari, Thomas Meitinger, Jesper V. Olsen, Gerjan Navis, Steven R. Cummings, Richard W Morris, Nynke Hofman, Marcel den Hoed, Rudolf A. de Boer, Gonçalo R. Abecasis, Mark J. Daly, Dan M. Roden, Christian Gieger, Lyudmyla Kedenko, Marcus Dörr, Thomas P. Cappola, Afshin Parsa, Kari Stefansson, Markus Perola, Mark Eijgelsheim, Fredrik Nyberg, Robert M. Hamilton, Yalda Jamshidi, W. H. Linda Kao, Terho Lehtimäki, Annette Peters, David Schlessinger, Peter P. Pramstaller, James F. Wilson, Vilmundur Gudnason, Florian Kronenberg, Aroon D. Hingorani, Connie R. Bezzina, Abdennasser Bardai, Marylyn D. Ritchie, Andrew S. Plump, Johan Sundström, Daryl Waggott, Chrysoula Dalageorgou, Paul I.W. de Bakker, Uwe Völker, Aaron Isaacs, Oscar H. Franco, Yongmei Liu, Andrew N. Nicolaides, Lia Crotti, Cornelia M. van Duijn, Ben A. Oostra, Arne Pfeufer, Karl Werdan, Michael Morley, Jan A. Kors, Julien Barc, Lewin Eisele, Siegfried Perz, Stéphanie Chatel, Pieter A. van der Vleuten, Sara L. Pulit, Anna F. Dominiczak, Harry Campbell, Alice Ghidoni, Irene Mateo Leach, Nona Sotoodehnia, Nina Mononen, Henriette E. Meyer zu Schwabedissen, Alvaro Alonso, Fabiola Del Greco M, Dan E. Arking, Vera Adamkova, Mike A. Nalls, Valur Emilsson, Edward G. Lakatta, Kirill Tarasov, Alan F. Wright, Lenore J. Launer, Erik Ingelsson, Karin Halina Greiser, Ozren Polasek, Massimo Carella, Daniel F. Gudbjartsson, Bouwe P. Krijthe, Hanna Prucha, Per Hoffmann, Maura Griffin, Stefan Kiechl, Angel Carracedo, Ilja M. Nolte, Christine E. Moravec, Johann Willeit, Joshua C. Bis, Patricia B. Munroe, Marcello Ricardo Paulista Markus, Hailiang Huang, Mika Kähönen, Albert Hofman, Peter H. Whincup, Dirk J. van Veldhuisen, Michael Knoflach, Alicia Lundby, Serena Sanna, Hagen Kälsch, Bernhard Paulweber, Kamil Slowikowski, Luigi Ferrucci, Melanie Waldenberger, Marco Bobbo, Annukka M. Lahtinen, Ann-Christine Syvänen, J. Gustav Smith, Åsa Torinsson Naluai, Jaroslav A. Hubacek, Jeffrey Brandimarto, Wendy S. Post, Lude Franke, Mark J. Caulfield, Folkert W. Asselbergs, André G. Uitterlinden, Stefan Gustafsson, Pim van der Harst, David J. Tester, David S. Siscovick, David O. Arnar, Sarah H Wild, Elizabeth J. Rossin, Albert V. Smith, Bruce M. Psaty, Georg Ehret, Alan R. Shuldiner, Stephen Newhouse, Kimmo Kontula, Maria Brion, Andre Franke, Peter W. Macfarlane, Mika Kivimäki, Tamara B. Harris, Lasse Oikarinen, Tamara T. Koopmann, Kenneth B. Margulies, Aravinda Chakravarti, Gianfranco Sinagra, Maarten P. van den Berg, Veikko Salomaa, Karl-Heinz Jöckel, Daniel S. Evans, Caroline Hayward, Kimmo Porthan, Michael J. Ackerman, Jacqueline C.M. Witteman, Arthur A.M. Wilde, Martin G. Larson, Kasper Lage, Manuela Uda, Susan R. Heckbert, Joel S. Bader, Graham Watt, María Dolores Torres, Stephan B. Felix, Jerome I. Rotter, Pau Navarro, Meena Kumari, Johan Ärnlöv, Andrew D. Paterson, Antti Jula, Olli T. Raitakari, Raimund Erbel, Christopher J. O'Donnell, Britt M. Beckmann, Peter A. Noseworthy, Tim D. Spector, Wai K. Lee, Leopoldo Zelante, Nilesh J. Samani, John R. Giudicessi, Harold Snieder, Dag S. Thelle, David Ellinghaus, Eimo Martens, James B. Strait, Jorma S. A. Viikari, Andrew D. Johnson, Antonella Mulas, Hilma Holm, Johannes Haerting, Annamaria Iorio, Rebecca L. Zuvich, Sheila Ulivi, Andrew A. Hicks, Elijah R. Behr, Leo-Pekka Lyytikäinen, Bernhard Strohmer, Marco Orru, Claudia Lamina, Sandosh Padmanabhan, Christian Fuchsberger, Andrie G. Panayiotou, Ehret, Georg Benedikt, Internal Medicine, Public Health, Epidemiology, Rehabilitation Medicine, Medical Informatics, Clinical Genetics, Cardiovascular Centre (CVC), Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Vascular Ageing Programme (VAP), Ethical, Legal, Social Issues in Genetics (ELSI), Stem Cell Aging Leukemia and Lymphoma (SALL), Arking, D, Pulit, S, Crotti, L, van der Harst, P, Munroe, P, Koopmann, T, Sotoodehnia, N, Rossin, E, Morley, M, Wang, X, Johnson, A, Lundby, A, Gudbjartsson, D, Noseworthy, P, Eijgelsheim, M, Bradford, Y, Tarasov, K, Dörr, M, Müller-Nurasyid, M, Lahtinen, A, Nolte, I, Smith, A, Bis, J, Isaacs, A, Newhouse, S, Evans, D, Post, W, Waggott, D, Lyytikäinen, L, Hicks, A, Eisele, L, Ellinghaus, D, Hayward, C, Navarro, P, Ulivi, S, Tanaka, T, Tester, D, Chatel, S, Gustafsson, S, Kumari, M, Morris, R, Naluai, A, Padmanabhan, S, Kluttig, A, Strohmer, B, Panayiotou, A, Torres, M, Knoflach, M, Hubacek, J, Slowikowski, K, Raychaudhuri, S, Kumar, R, Harris, T, Launer, L, Shuldiner, A, Alonso, A, Bader, J, Ehret, G, Huang, H, Kao, W, Strait, J, Macfarlane, P, Brown, M, Caulfield, M, Samani, N, Kronenberg, F, Willeit, J, Smith, J, Greiser, K, Meyer Zu Schwabedissen, H, Werdan, K, Carella, M, Zelante, L, Heckbert, S, Psaty, B, Rotter, J, Kolcic, I, Polašek, O, Wright, A, Griffin, M, Daly, M, Arnar, D, Hólm, H, Thorsteinsdottir, U, Denny, J, Roden, D, Zuvich, R, Emilsson, V, Plump, A, Larson, M, O'Donnell, C, Yin, X, Bobbo, M, D'Adamo, A, Iorio, A, Sinagra, G, Carracedo, A, Cummings, S, Nalls, M, Jula, A, Kontula, K, Marjamaa, A, Oikarinen, L, Perola, M, Porthan, K, Erbel, R, Hoffmann, P, Jöckel, K, Kälsch, H, Nöthen, M, den Hoed, M, Loos, R, Thelle, D, Gieger, C, Meitinger, T, Perz, S, Peters, A, Prucha, H, Sinner, M, Waldenberger, M, de Boer, R, Franke, L, van der Vleuten, P, Beckmann, B, Martens, E, Bardai, A, Hofman, N, Wilde, A, Behr, E, Dalageorgou, C, Giudicessi, J, Medeiros-Domingo, A, Kyndt, F, Probst, V, Ghidoni, A, Insolia, R, Hamilton, R, Scherer, S, Brandimarto, J, Margulies, K, Moravec, C, Greco, M, Fuchsberger, C, O'Connell, J, Lee, W, Watt, G, Campbell, H, Wild, S, El Mokhtari, N, Frey, N, Asselbergs, F, Mateo Leach, I, Navis, G, van den Berg, M, van Veldhuisen, D, Kellis, M, Krijthe, B, Franco, O, Hofman, A, Kors, J, Uitterlinden, A, Witteman, J, Kedenko, L, Lamina, C, Oostra, B, Abecasis, G, Lakatta, E, Mulas, A, Orrú, M, Schlessinger, D, Uda, M, Markus, M, Völker, U, Snieder, H, Spector, T, Arnlöv, J, Lind, L, Sundström, J, Syvänen, A, Kivimaki, M, Kähönen, M, Mononen, N, Raitakari, O, Viikari, J, Adamkova, V, Kiechl, S, Brion, M, Nicolaides, A, Paulweber, B, Haerting, J, Dominiczak, A, Nyberg, F, Whincup, P, Hingorani, A, Schott, J, Bezzina, C, Ingelsson, E, Ferrucci, L, Gasparini, P, Wilson, J, Rudan, I, Franke, A, Mühleisen, T, Pramstaller, P, Lehtimäki, T, Paterson, A, Parsa, A, Liu, Y, van Duijn, C, Siscovick, D, Gudnason, V, Jamshidi, Y, Salomaa, V, Felix, S, Sanna, S, Ritchie, M, Stricker, B, Stefansson, K, Boyer, L, Cappola, T, Olsen, J, Lage, K, Schwartz, P, Kääb, S, Chakravarti, A, Ackerman, M, Pfeufer, A, de Bakker, P, Newton-Cheh, C, Arking, Dan E., Pulit, Sara L., Crotti, Lia, Van Der Harst, Pim, Munroe, Patricia B., Koopmann, Tamara T., Sotoodehnia, Nona, Rossin, Elizabeth J., Morley, Michael, Wang, Xinchen, Johnson, Andrew D., Lundby, Alicia, Gudbjartsson, Daníel F., Noseworthy, Peter A., Eijgelsheim, Mark, Bradford, Yuki, Tarasov, Kirill V., Dörr, Marcu, Müller Nurasyid, Martina, Lahtinen, Annukka M., Nolte, Ilja M., Smith, Albert Vernon, Bis, Joshua C., Isaacs, Aaron, Newhouse, Stephen J., Evans, Daniel S., Post, Wendy S., Waggott, Daryl, Lyytikäinen, Leo Pekka, Hicks, Andrew A., Eisele, Lewin, Ellinghaus, David, Hayward, Caroline, Navarro, Pau, Ulivi, Sheila, Tanaka, Toshiko, Tester, David J., Chatel, Stéphanie, Gustafsson, Stefan, Kumari, Meena, Morris, Richard W., Naluai, Asa T., Padmanabhan, Sandosh, Kluttig, Alexander, Strohmer, Bernhard, Panayiotou, Andrie G., Torres, Maria, Knoflach, Michael, Hubacek, Jaroslav A., Slowikowski, Kamil, Raychaudhuri, Soumya, Kumar, Runjun D., Harris, Tamara B., Launer, Lenore J., Shuldiner, Alan R., Alonso, Alvaro, Bader, Joel S., Ehret, Georg, Huang, Hailiang, Kao, W. H. Linda, Strait, James B., Macfarlane, Peter W., Brown, Morri, Caulfield, Mark J., Samani, Nilesh J., Kronenberg, Florian, Willeit, Johann, Smith, J. Gustav, Greiser, Karin H., Zu Schwabedissen, Henriette Meyer, Werdan, Karl, Carella, Massimo, Zelante, Leopoldo, Heckbert, Susan R., Psaty, Bruce M., Rotter, Jerome I., Kolcic, Ivana, Polašek, Ozren, Wright, Alan F., Griffin, Maura, Daly, Mark J., Arnar, David O., Hólm, Hilma, Thorsteinsdottir, Unnur, Denny, Joshua C., Roden, Dan M., Zuvich, Rebecca L., Emilsson, Valur, Plump, Andrew S., Larson, Martin G., O'Donnell, Christopher J., Yin, Xiaoyan, Bobbo, Marco, D'Adamo, ADAMO PIO, Iorio, Annamaria, Sinagra, Gianfranco, Carracedo, Angel, Cummings, Steven R., Nalls, Michael A., Jula, Antti, Kontula, Kimmo K., Marjamaa, Annukka, Oikarinen, Lasse, Perola, Marku, Porthan, Kimmo, Erbel, Raimund, Hoffmann, Per, Jöckel, Karl Heinz, Kälsch, Hagen, Nöthen, Markus M., Den Hoed, Marcel, Loos, Ruth J. F., Thelle, Dag S., Gieger, Christian, Meitinger, Thoma, Perz, Siegfried, Peters, Annette, Prucha, Hanna, Sinner, Moritz F., Waldenberger, Melanie, De Boer, Rudolf A., Franke, Lude, Van Der Vleuten, Pieter A., Beckmann, Britt Maria, Martens, Eimo, Bardai, Abdennasser, Hofman, Nynke, Wilde, Arthur A. M., Behr, Elijah R., Dalageorgou, Chrysoula, Giudicessi, John R., Medeiros Domingo, Argelia, Barc, Julien, Kyndt, Florence, Probst, Vincent, Ghidoni, Alice, Insolia, Roberto, Hamilton, Robert M., Scherer, Stephen W., Brandimarto, Jeffrey, Margulies, Kenneth, Moravec, Christine E., Del Greco M, Fabiola, Fuchsberger, Christian, O'Connell, Jeffrey R., Lee, Wai K., Watt, Graham C. M., Campbell, Harry, Wild, Sarah H., El Mokhtari, Nour E., Frey, Norbert, Asselbergs, Folkert W., Leach, Irene Mateo, Navis, Gerjan, Van Den Berg, Maarten P., Van Veldhuisen, Dirk J., Kellis, Manoli, Krijthe, Bouwe P., Franco, Oscar H., Hofman, Albert, Kors, Jan A., Uitterlinden, André G., Witteman, Jacqueline C. M., Kedenko, Lyudmyla, Lamina, Claudia, Oostra, Ben A., Abecasis, Gonçalo R., Lakatta, Edward G., Mulas, Antonella, Orrú, Marco, Schlessinger, David, Uda, Manuela, Markus, Marcello R. P., Völker, Uwe, Snieder, Harold, Spector, Timothy D., Ärnlöv, Johan, Lind, Lar, Sundström, Johan, Syvänen, Ann Christine, Kivimaki, Mika, Kähönen, Mika, Mononen, Nina, Raitakari, Olli T., Viikari, Jorma S., Adamkova, Vera, Kiechl, Stefan, Brion, Maria, Nicolaides, Andrew N., Paulweber, Bernhard, Haerting, Johanne, Dominiczak, Anna F., Nyberg, Fredrik, Whincup, Peter H., Hingorani, Aroon D., Schott, Jean Jacque, Bezzina, Connie R., Ingelsson, Erik, Ferrucci, Luigi, Gasparini, Paolo, Wilson, James F., Rudan, Igor, Franke, Andre, Mühleisen, Thomas W., Pramstaller, Peter P., Lehtimäki, Terho J., Paterson, Andrew D., Parsa, Afshin, Liu, Yongmei, Van Duijn, Cornelia M., Siscovick, David S., Gudnason, Vilmundur, Jamshidi, Yalda, Salomaa, Veikko, Felix, Stephan B., Sanna, Serena, Ritchie, Marylyn D., Stricker, Bruno H., Stefansson, Kari, Boyer, Laurie A., Cappola, Thomas P., Olsen, Jesper V., Lage, Kasper, Schwartz, Peter J., Kääb, Stefan, Chakravarti, Aravinda, Ackerman, Michael J., Pfeufer, Arne, De Bakker, Paul I. W., Newton Cheh, Christopher, Cardiology, ACS - Amsterdam Cardiovascular Sciences, and Human Genetics
Subjects: Male, Candidate gene, Myocardium/metabolism, LOCI, Medizin, Heart electrophysiology, Genome-wide association study, Arrhythmias, Bioinformatics, Medical and Health Sciences, Heart Ventricle, Sudden cardiac death, Electrocardiography, PR INTERVAL, Arrhythmias, Cardiac/genetics, Death, Sudden, Cardiac/etiology, Genetics, ddc:616, Cardiac electrophysiology, Adult, Aged, Arrhythmias, Cardiac, Calcium Signaling, Death, Sudden, Cardiac, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Heart Ventricles, Humans, Long QT Syndrome, Middle Aged, Myocardium, Polymorphism, Single Nucleotide, COMMON VARIANTS, Heart Ventricles/metabolism, Single Nucleotide, Long QT Syndrome/genetics, CHRONIC HEART-FAILURE, Death, Heart ventricle arrhythmia, genetic association study, gene, SNP, heart, Genome-Wide Association Study/methods, Long QT syndrome, QRS DURATION, Cardiac, Cardiac/etiology, Human, QT interval, congenital, hereditary, and neonatal diseases and abnormalities, Electrocardiography/methods, TRPM7, BIO/18 - GENETICA, Cardiac/genetics, Biology, Article, sudden cardiac death, QRS complex, CARDIAC REPOLARIZATION, medicine, Repolarization, cardiovascular diseases, GENOME-WIDE ASSOCIATION, Polymorphism, MED/01 - STATISTICA MEDICA, calcium, ta1184, Calcium signaling, Calcium Signaling/genetics, MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, ta3121, Cardiovascular risk, medicine.disease, SARCOPLASMIC-RETICULUM, Sudden, MODEL, Genetic association, myocardial repolarization, Genetic variability, Gene expression, Clinical Medicine, genetic, Controlled study
Abstract: The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain similar to 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.
Published: 2014

15. Integrated landscape of cardiac metabolism in end-stage human nonischemic dilated cardiomyopathy.

Author: Flam E, Jang C, Murashige D, Yang Y, Morley MP, Jung S, Kantner DS, Pepper H, Bedi KC Jr, Brandimarto J, Prosser BL, Cappola T, Snyder NW, Rabinowitz JD, Margulies KB, and Arany Z
Abstract: Heart failure (HF) is a leading cause of mortality. Failing hearts undergo profound metabolic changes, but a comprehensive evaluation in humans is lacking. We integrate plasma and cardiac tissue metabolomics of 678 metabolites, genome-wide RNA-sequencing, and proteomic studies to examine metabolic status in 87 explanted human hearts from 39 patients with end-stage HF compared with 48 nonfailing donors. We confirm bioenergetic defects in human HF and reveal selective depletion of adenylate purines required for maintaining ATP levels. We observe substantial reductions in fatty acids and acylcarnitines in failing tissue, despite plasma elevations, suggesting defective import of fatty acids into cardiomyocytes. Glucose levels, in contrast, are elevated. Pyruvate dehydrogenase, which gates carbohydrate oxidation, is de-repressed, allowing increased lactate and pyruvate burning. Tricarboxylic acid cycle intermediates are significantly reduced. Finally, bioactive lipids are profoundly reprogrammed, with marked reductions in ceramides and elevations in lysoglycerophospholipids. These data unveil profound metabolic abnormalities in human failing hearts., Competing Interests: Competing interests The authors declare no competing interests.
Published: 2022
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16. Genomic Context Differs Between Human Dilated Cardiomyopathy and Hypertrophic Cardiomyopathy.

Author: Puckelwartz MJ, Pesce LL, Dellefave-Castillo LM, Wheeler MT, Pottinger TD, Robinson AC, Kearns SD, Gacita AM, Schoppen ZJ, Pan W, Kim G, Wilcox JE, Anderson AS, Ashley EA, Day SM, Cappola T, Dorn GW 2nd, and McNally EM
Subjects: Adult, Cardiomyopathy, Dilated diagnosis, Cardiomyopathy, Dilated physiopathology, Cardiomyopathy, Hypertrophic diagnosis, Cardiomyopathy, Hypertrophic physiopathology, Female, Genomics, Genotype, Heart Ventricles physiopathology, Humans, Male, Middle Aged, Cardiomyopathy, Dilated genetics, Cardiomyopathy, Hypertrophic genetics, Echocardiography methods, Heart Ventricles diagnostic imaging, Polymorphism, Single Nucleotide, Stroke Volume physiology, Ventricular Function, Left physiology
Abstract: Background Inherited cardiomyopathies display variable penetrance and expression, and a component of phenotypic variation is genetically determined. To evaluate the genetic contribution to this variable expression, we compared protein coding variation in the genomes of those with hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Methods and Results Nonsynonymous single-nucleotide variants (nsSNVs) were ascertained using whole genome sequencing from familial cases of HCM (n=56) or DCM (n=70) and correlated with echocardiographic information. Focusing on nsSNVs in 102 genes linked to inherited cardiomyopathies, we correlated the number of nsSNVs per person with left ventricular measurements. Principal component analysis and generalized linear models were applied to identify the probability of cardiomyopathy type as it related to the number of nsSNVs in cardiomyopathy genes. The probability of having DCM significantly increased as the number of cardiomyopathy gene nsSNVs per person increased. The increase in nsSNVs in cardiomyopathy genes significantly associated with reduced left ventricular ejection fraction and increased left ventricular diameter for individuals carrying a DCM diagnosis, but not for those with HCM. Resampling was used to identify genes with aberrant cumulative allele frequencies, identifying potential modifier genes for cardiomyopathy. Conclusions Participants with DCM had more nsSNVs per person in cardiomyopathy genes than participants with HCM. The nsSNV burden in cardiomyopathy genes did not correlate with the probability or manifestation of left ventricular measures in HCM. These findings support the concept that increased variation in cardiomyopathy genes creates a genetic background that predisposes to DCM and increased disease severity.
Published: 2021
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17. Clinical and Proteomic Correlates of Plasma ACE2 (Angiotensin-Converting Enzyme 2) in Human Heart Failure.

Author: Chirinos JA, Cohen JB, Zhao L, Hanff T, Sweitzer N, Fang J, Corrales-Medina V, Anmar R, Morley M, Zamani P, Bhattacharya P, Brandimarto J, Jia Y, Basso MD, Wang Z, Ebert C, Ramirez-Valle F, Schafer PH, Seiffert D, Gordon DA, and Cappola T
Subjects: Academic Medical Centers, Analysis of Variance, Angiotensin-Converting Enzyme 2, Biomarkers metabolism, COVID-19, Cohort Studies, Coronavirus Infections prevention & control, Female, Humans, Linear Models, Male, Middle Aged, Pandemics prevention & control, Pneumonia, Viral prevention & control, Prognosis, Proportional Hazards Models, Proteomics methods, Retrospective Studies, Sensitivity and Specificity, Severity of Illness Index, United States, Coronavirus Infections epidemiology, Disease Outbreaks statistics & numerical data, Disease Progression, Heart Failure enzymology, Heart Failure physiopathology, Peptidyl-Dipeptidase A blood, Pneumonia, Viral epidemiology
Abstract: ACE2 (angiotensin-converting enzyme 2) is a key component of the renin-angiotensin-aldosterone system. Yet, little is known about the clinical and biologic correlates of circulating ACE2 levels in humans. We assessed the clinical and proteomic correlates of plasma (soluble) ACE2 protein levels in human heart failure. We measured plasma ACE2 using a modified aptamer assay among PHFS (Penn Heart Failure Study) participants (n=2248). We performed an association study of ACE2 against ≈5000 other plasma proteins measured with the SomaScan platform. Plasma ACE2 was not associated with ACE inhibitor and angiotensin-receptor blocker use. Plasma ACE2 was associated with older age, male sex, diabetes mellitus, a lower estimated glomerular filtration rate, worse New York Heart Association class, a history of coronary artery bypass surgery, and higher pro-BNP (pro-B-type natriuretic peptide) levels. Plasma ACE2 exhibited associations with 1011 other plasma proteins. In pathway overrepresentation analyses, top canonical pathways associated with plasma ACE2 included clathrin-mediated endocytosis signaling, actin cytoskeleton signaling, mechanisms of viral exit from host cells, EIF2 (eukaryotic initiation factor 2) signaling, and the protein ubiquitination pathway. In conclusion, in humans with heart failure, plasma ACE2 is associated with various clinical factors known to be associated with severe coronavirus disease 2019 (COVID-19), including older age, male sex, and diabetes mellitus, but is not associated with ACE inhibitor and angiotensin-receptor blocker use. Plasma ACE2 protein levels are prominently associated with multiple cellular pathways involved in cellular endocytosis, exocytosis, and intracellular protein trafficking. Whether these have a causal relationship with ACE2 or are relevant to novel coronavirus-2 infection remains to be assessed in future studies.
Published: 2020
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18. Clinical Phenogroups in Heart Failure With Preserved Ejection Fraction: Detailed Phenotypes, Prognosis, and Response to Spironolactone.

Author: Cohen JB, Schrauben SJ, Zhao L, Basso MD, Cvijic ME, Li Z, Yarde M, Wang Z, Bhattacharya PT, Chirinos DA, Prenner S, Zamani P, Seiffert DA, Car BD, Gordon DA, Margulies K, Cappola T, and Chirinos JA
Subjects: Aged, Echocardiography, Female, Heart Failure diagnosis, Heart Failure physiopathology, Humans, Male, Middle Aged, Mineralocorticoid Receptor Antagonists therapeutic use, Phenotype, Prognosis, Treatment Outcome, Ventricular Remodeling drug effects, Heart Failure drug therapy, Spironolactone therapeutic use, Stroke Volume physiology, Ventricular Remodeling physiology
Abstract: Objectives: This study sought to assess if clinical phenogroups differ in comprehensive biomarker profiles, cardiac and arterial structure/function, and responses to spironolactone therapy., Background: Previous studies identified distinct subgroups (phenogroups) of patients with heart failure with preserved ejection fraction (HFpEF)., Methods: Among TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial) participants, we performed latent-class analysis to identify HFpEF phenogroups based on standard clinical features and assessed differences in multiple biomarkers measured from frozen plasma; cardiac and arterial structure/function measured with echocardiography and arterial tonometry; prognosis; and response to spironolactone., Results: Three HFpEF phenogroups were identified. Phenogroup 1 (n = 1,214) exhibited younger age, higher prevalence of smoking, preserved functional class, and the least evidence of left ventricular (LV) hypertrophy and arterial stiffness. Phenogroup 2 (n = 1,329) was older, with normotrophic concentric LV remodeling, atrial fibrillation, left atrial enlargement, large-artery stiffening, and biomarkers of innate immunity and vascular calcification. Phenogroup 3 (n = 899) demonstrated more functional impairment, obesity, diabetes, chronic kidney disease, concentric LV hypertrophy, high renin, and biomarkers of tumor necrosis factor-alpha-mediated inflammation, liver fibrosis, and tissue remodeling. Compared with phenogroup 1, phenogroup 3 exhibited the highest risk of the primary endpoint of cardiovascular death, heart failure hospitalization, or aborted cardiac arrest (hazard ratio [HR]: 3.44; 95% confidence interval [CI]: 2.79 to 4.24); phenogroups 2 and 3 demonstrated similar all-cause mortality (phenotype 2 HR: 2.36; 95% CI: 1.89 to 2.95; phenotype 3 HR: 2.26, 95% CI: 1.77 to 2.87). Spironolactone randomized therapy was associated with a more pronounced reduction in the risk of the primary endpoint in phenogroup 3 (HR: 0.75; 95% CI: 0.59 to 0.95; p for interaction = 0.016). Results were similar after excluding participants from Eastern Europe., Conclusions: We identified important differences in circulating biomarkers, cardiac/arterial characteristics, prognosis, and response to spironolactone across clinical HFpEF phenogroups. These findings suggest distinct underlying mechanisms across clinically identifiable phenogroups of HFpEF that may benefit from different targeted interventions., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
Published: 2020
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19. Antisense regulation of atrial natriuretic peptide expression.

Author: Celik S, Sadegh MK, Morley M, Roselli C, Ellinor PT, Cappola T, Smith JG, and Gidlöf O
Subjects: Animals, Chromatin, Gene Expression Regulation, Gene Knockdown Techniques, Heart Failure, Humans, Male, Mice, Inbred C57BL, Myocardium metabolism, Neprilysin, RNA, Messenger metabolism, Transcription Factors, Atrial Natriuretic Factor genetics, Atrial Natriuretic Factor metabolism, Myocytes, Cardiac metabolism
Abstract: The cardiac hormone atrial natriuretic peptide (ANP) is a central regulator of blood volume and a therapeutic target in hypertension and heart failure. Enhanced ANP activity in such conditions through inhibition of the degradative enzyme neprilysin has shown clinical efficacy but is complicated by consequences of simultaneous accumulation of a heterogeneous array of other hormones. Targets for specific ANP enhancement have not been available. Here, we describe a cis-acting antisense transcript (NPPA-AS1), which negatively regulates ANP expression in human cardiomyocytes. We show that NPPA-AS1 regulates ANP expression via facilitating NPPA repressor RE1-silencing transcription factor (REST) binding to its promoter, rather than forming an RNA duplex with ANP mRNA. Expression of ANP mRNA and NPPA-AS1 was increased and correlated in isolated strained human cardiomyocytes and in hearts from patients with advanced heart failure. Further, inhibition of NPPA-AS1 in vitro and in vivo resulted in increased myocardial expression of ANP, increased circulating ANP, increased renal cGMP, and lower blood pressure. The effects of NPPA-AS1 inhibition on NPPA expression in human cardiomyocytes were further marked under cell-strain conditions. Collectively, these results implicate the antisense transcript NPPA-AS1 as part of a physiologic self-regulatory ANP circuit and a viable target for specific ANP augmentation.
Published: 2019
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20. Pathologic gene network rewiring implicates PPP1R3A as a central regulator in pressure overload heart failure.

Author: Cordero P, Parikh VN, Chin ET, Erbilgin A, Gloudemans MJ, Shang C, Huang Y, Chang AC, Smith KS, Dewey F, Zaleta K, Morley M, Brandimarto J, Glazer N, Waggott D, Pavlovic A, Zhao M, Moravec CS, Tang WHW, Skreen J, Malloy C, Hannenhalli S, Li H, Ritter S, Li M, Bernstein D, Connolly A, Hakonarson H, Lusis AJ, Margulies KB, Depaoli-Roach AA, Montgomery SB, Wheeler MT, Cappola T, and Ashley EA
Subjects: Animals, Benzeneacetamides, Cells, Cultured, Datasets as Topic, Disease Models, Animal, Female, Gene Expression Profiling methods, Gene Expression Regulation, Gene Knockdown Techniques, Genome-Wide Association Study, Heart Failure etiology, Heart Failure metabolism, Heart Failure pathology, Humans, Male, Metabolic Networks and Pathways genetics, Mice, Mice, Knockout, Middle Aged, Phosphoprotein Phosphatases genetics, Primary Cell Culture, Pyridines, Quantitative Trait Loci genetics, Rats, Rats, Sprague-Dawley, Sequence Analysis, RNA methods, Gene Regulatory Networks genetics, Heart Failure genetics, Myocytes, Cardiac pathology, Phosphoprotein Phosphatases metabolism
Abstract: Heart failure is a leading cause of mortality, yet our understanding of the genetic interactions underlying this disease remains incomplete. Here, we harvest 1352 healthy and failing human hearts directly from transplant center operating rooms, and obtain genome-wide genotyping and gene expression measurements for a subset of 313. We build failing and non-failing cardiac regulatory gene networks, revealing important regulators and cardiac expression quantitative trait loci (eQTLs). PPP1R3A emerges as a regulator whose network connectivity changes significantly between health and disease. RNA sequencing after PPP1R3A knockdown validates network-based predictions, and highlights metabolic pathway regulation associated with increased cardiomyocyte size and perturbed respiratory metabolism. Mice lacking PPP1R3A are protected against pressure-overload heart failure. We present a global gene interaction map of the human heart failure transition, identify previously unreported cardiac eQTLs, and demonstrate the discovery potential of disease-specific networks through the description of PPP1R3A as a central regulator in heart failure.
Published: 2019
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21. Genomic Risk Stratification Predicts All-Cause Mortality After Cardiac Catheterization.

Author: Levin MG, Kember RL, Judy R, Birtwell D, Williams H, Arany Z, Giri J, Guerraty M, Cappola T, Chen J, Rader DJ, and Damrauer SM
Subjects: Aged, Aged, 80 and over, Cohort Studies, Disease-Free Survival, Female, Humans, Male, Middle Aged, Risk Assessment, Risk Factors, Survival Rate, Cardiac Catheterization, Coronary Angiography, Coronary Artery Disease diagnostic imaging, Coronary Artery Disease genetics, Coronary Artery Disease mortality, Coronary Artery Disease therapy, Myocardial Infarction diagnostic imaging, Myocardial Infarction genetics, Myocardial Infarction mortality, Myocardial Infarction therapy
Abstract: Background: Coronary artery disease (CAD) is influenced by genetic variation and traditional risk factors. Polygenic risk scores (PRS), which can be ascertained before the development of traditional risk factors, have been shown to identify individuals at elevated risk of CAD. Here, we demonstrate that a genome-wide PRS for CAD predicts all-cause mortality after accounting for not only traditional cardiovascular risk factors but also angiographic CAD itself., Methods: Individuals who underwent coronary angiography and were enrolled in an institutional biobank were included; those with prior myocardial infarction or heart transplant were excluded. Using a pruning-and-thresholding approach, a genome-wide PRS comprised of 139 239 variants was calculated for 1503 participants who underwent coronary angiography and genotyping. Individuals were categorized into high PRS (hiPRS) and low-PRS control groups using the maximally selected rank statistic. Stratified analysis based on angiographic findings was also performed. The primary outcome was all-cause mortality following the index coronary angiogram., Results: Individuals with hiPRS were younger than controls (66 years versus 69 years; P=2.1×10 -5 ) but did not differ by sex, body mass index, or traditional risk-factor profiles. Individuals with hiPRS were at significantly increased risk of all-cause mortality after cardiac catheterization, adjusting for traditional risk factors and angiographic extent of CAD (hazard ratio, 1.6; 95% CI, 1.2-2.2; P=0.004). The strongest increase in risk of all-cause mortality conferred by hiPRS was seen among individuals without angiographic CAD (hazard ratio, 2.4; 95% CI, 1.1-5.5; P=0.04). In the overall cohort, adding hiPRS to traditional risk assessment improved prediction of 5-year all-cause mortality (area under the receiver-operating curve 0.70; 95% CI, 0.66-0.75 versus 0.66; 95% CI, 0.61-0.70; P=0.001)., Conclusions: A genome-wide PRS improves risk stratification when added to traditional risk factors and coronary angiography. Individuals without angiographic CAD but with hiPRS remain at significantly elevated risk of mortality.
Published: 2018
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22. Associations of Conventional Echocardiographic Measures with Incident Heart Failure and Mortality: The Chronic Renal Insufficiency Cohort.

Author: Dubin RF, Deo R, Bansal N, Anderson AH, Yang P, Go AS, Keane M, Townsend R, Porter A, Budoff M, Malik S, He J, Rahman M, Wright J, Cappola T, Kallem R, Roy J, Sha D, and Shlipak MG
Subjects: Aged, Echocardiography, Female, Follow-Up Studies, Heart Failure physiopathology, Heart Ventricles diagnostic imaging, Humans, Hypertrophy, Left Ventricular diagnostic imaging, Hypertrophy, Left Ventricular physiopathology, Incidence, Male, Middle Aged, Organ Size, Stroke Volume, Cause of Death, Heart Failure epidemiology, Heart Ventricles pathology, Hypertrophy, Left Ventricular epidemiology, Renal Insufficiency, Chronic epidemiology
Abstract: Background and Objectives: Heart failure is the most frequent cardiac complication of CKD. Left ventricular hypertrophy is common and develops early in CKD, but studies have not adequately evaluated the association of left ventricular mass index with heart failure incidence among men and women with CKD., Design, Setting, Participants, & Measurements: We evaluated echocardiograms of 2567 participants without self-reported heart failure enrolled in the Chronic Renal Insufficiency Cohort Study. Two-dimensional echocardiograms were performed at the year 1 study visit and interpreted at a central core laboratory. Left ventricular mass index was calculated using the linear method, indexed to height 2.7 , and analyzed using sex-specific quartiles. The primary outcomes of incident heart failure and all-cause mortality were adjudicated over a median of 6.6 (interquartile range, 5.7-7.6) years., Results: Among 2567 participants, 45% were women, and 54% were nonwhite race; mean (SD) age was 59±11 years old, and mean eGFR was 44±17 ml/min per 1.73 m 2 . During a median follow-up period of 6.6 years, 262 participants developed heart failure, and 470 participants died. Compared with participants in the first quartile of left ventricular mass index, those in the highest quartile had higher rates of incident heart failure (hazard ratio, 3.96; 95% confidence interval, 1.96 to 8.02) and mortality (hazard ratio, 1.86; 95% confidence interval, 1.22 to 2.85), even after adjustment for B-type natriuretic peptide, troponin T, mineral metabolism markers, and other cardiovascular disease risk factors. Those in the lowest quartile of ejection fraction had higher rates of incident heart failure (hazard ratio, 3.01; 95% confidence interval, 1.94 to 4.67) but similar mortality rates (hazard ratio, 1.18; 95% confidence interval, 0.89 to 1.57) compared with those in the highest quartile. Diastolic dysfunction was not significantly associated with heart failure or death., Conclusions: Among persons with CKD and without history of cardiovascular disease, left ventricular mass index is strongly associated with incident heart failure, even after adjustment for major cardiovascular risk factors and biomarkers., (Copyright © 2016 by the American Society of Nephrology.)
Published: 2017
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23. Causal Assessment of Serum Urate Levels in Cardiometabolic Diseases Through a Mendelian Randomization Study.

Author: Keenan T, Zhao W, Rasheed A, Ho WK, Malik R, Felix JF, Young R, Shah N, Samuel M, Sheikh N, Mucksavage ML, Shah O, Li J, Morley M, Laser A, Mallick NH, Zaman KS, Ishaq M, Rasheed SZ, Memon FU, Ahmed F, Hanif B, Lakhani MS, Fahim M, Ishaq M, Shardha NK, Ahmed N, Mahmood K, Iqbal W, Akhtar S, Raheel R, O'Donnell CJ, Hengstenberg C, März W, Kathiresan S, Samani N, Goel A, Hopewell JC, Chambers J, Cheng YC, Sharma P, Yang Q, Rosand J, Boncoraglio GB, Kazmi SU, Hakonarson H, Köttgen A, Kalogeropoulos A, Frossard P, Kamal A, Dichgans M, Cappola T, Reilly MP, Danesh J, Rader DJ, Voight BF, and Saleheen D
Subjects: Coronary Disease blood, Coronary Disease epidemiology, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 epidemiology, Global Health, Humans, Morbidity trends, Odds Ratio, Prognosis, Risk Factors, Stroke blood, Stroke epidemiology, Coronary Disease genetics, Diabetes Mellitus, Type 2 genetics, Mendelian Randomization Analysis methods, Polymorphism, Single Nucleotide, Risk Assessment methods, Stroke genetics, Uric Acid blood
Abstract: Background: Although epidemiological studies have reported positive associations between circulating urate levels and cardiometabolic diseases, causality remains uncertain., Objectives: Through a Mendelian randomization approach, we assessed whether serum urate levels are causally relevant in type 2 diabetes mellitus (T2DM), coronary heart disease (CHD), ischemic stroke, and heart failure (HF)., Methods: This study investigated 28 single nucleotide polymorphisms known to regulate serum urate levels in association with various vascular and nonvascular risk factors to assess pleiotropy. To limit genetic confounding, 14 single nucleotide polymorphisms exclusively associated with serum urate levels were used in a genetic risk score to assess associations with the following cardiometabolic diseases (cases/controls): T2DM (26,488/83,964), CHD (54,501/68,275), ischemic stroke (14,779/67,312), and HF (4,526/18,400). As a positive control, this study also investigated our genetic instrument in 3,151 gout cases and 68,350 controls., Results: Serum urate levels, increased by 1 SD due to the genetic score, were not associated with T2DM, CHD, ischemic stroke, or HF. These results were in contrast with previous prospective studies that did observe increased risks of these 4 cardiometabolic diseases for an equivalent increase in circulating urate levels. However, a 1 SD increase in serum urate levels due to the genetic score was associated with increased risk of gout (odds ratio: 5.84; 95% confidence interval: 4.56 to 7.49), which was directionally consistent with previous observations., Conclusions: Evidence from this study does not support a causal role of circulating serum urate levels in T2DM, CHD, ischemic stroke, or HF. Decreasing serum urate levels may not translate into risk reductions for cardiometabolic conditions., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
Published: 2016
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24. Systems Genomics Identifies a Key Role for Hypocretin/Orexin Receptor-2 in Human Heart Failure.

Author: Perez MV, Pavlovic A, Shang C, Wheeler MT, Miller CL, Liu J, Dewey FE, Pan S, Thanaporn PK, Absher D, Brandimarto J, Salisbury H, Chan K, Mukherjee R, Konadhode RP, Myers RM, Sedehi D, Scammell TE, Quertermous T, Cappola T, and Ashley EA
Subjects: Adult, Aged, Animals, Cohort Studies, Disease Models, Animal, Female, Genome-Wide Association Study, Heart Failure physiopathology, Humans, Male, Mice, Middle Aged, Heart Failure genetics, Heart Failure therapy, Orexin Receptors genetics, Stroke Volume genetics
Abstract: Background: The genetic determinants of heart failure (HF) and response to medical therapy remain unknown. We hypothesized that identifying genetic variants of HF that associate with response to medical therapy would elucidate the genetic basis of cardiac function., Objectives: This study sought to identify genetic variations associated with response to HF therapy., Methods: This study compared extremes of response to medical therapy in 866 HF patients using a genome-wide approach that informed the systems-based design of a customized single nucleotide variant array. The effect of genotype on gene expression was measured using allele-specific luciferase reporter assays. Candidate gene transcription-deficient mice underwent echocardiography and treadmill exercise. The ability of the target gene agonist to rescue mice from chemically-induced HF was assessed with echocardiography., Results: Of 866 HF patients, 136 had an ejection fraction improvement of 20% attributed to resynchronization (n = 83), revascularization (n = 7), tachycardia resolution (n = 2), alcohol cessation (n = 1), or medications (n = 43). Those with the minor allele for rs7767652, upstream of hypocretin (orexin) receptor-2 (HCRTR2), were less likely to have improved left ventricular function (odds ratio: 0.40 per minor allele; p = 3.29 × 10(-5)). In a replication cohort of 798 patients, those with a minor allele for rs7767652 had a lower prevalence of ejection fraction >35% (odds ratio: 0.769 per minor allele; p = 0.021). In an HF model, HCRTR2-deficient mice exhibited poorer cardiac function, worse treadmill exercise capacity, and greater myocardial scarring. Orexin, an HCRTR2 agonist, rescued function in this HF mouse model., Conclusions: A systems approach identified a novel genetic contribution to human HF and a promising therapeutic agent efficacious in an HF model., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
Published: 2015
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25. Response to letter regarding article, "Heart failure with recovered ejection fraction: clinical description, biomarkers, and outcomes".

Author: Basuray A, French B, Ky B, Vorovich E, Olt C, Sweitzer N, Cappola T, and Fang JC
Subjects: Female, Humans, Male, Ultrasonography, Heart Failure diagnostic imaging, Heart Failure physiopathology, Stroke Volume physiology
Published: 2015
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26. Symptoms characteristic of heart failure among CKD patients without diagnosed heart failure.

Author: Shlipak MG, Lash JP, Yang W, Teal V, Keane M, Cappola T, Keller C, Jamerson K, Kusek J, Delafontaine P, He J, Miller ER 3rd, Schreiber M, and Go AS
Subjects: Aged, Cohort Studies, Female, Heart Failure physiopathology, Humans, Kidney Failure, Chronic physiopathology, Male, Middle Aged, Surveys and Questionnaires standards, Heart Failure complications, Heart Failure diagnosis, Kidney Failure, Chronic complications, Kidney Failure, Chronic diagnosis
Abstract: Background: Epidemiological studies typically diagnose heart failure (HF) at the time of hospitalization, and have not evaluated the prevalence of HF symptoms in CKD patients without a prior HF diagnosis., Methods and Results: We modified the Kansas City Cardiomyopathy Questionnaire (KCCQ) to detect and quantify symptoms characteristic of HF (dyspnea, edema, and fatigue) among 2883 chronic kidney disease (CKD) patients without diagnosed heart failure in the Chronic Renal Insufficiency Cohort (CRIC). The KCCQ is a 23-item instrument that quantifies the impact of dyspnea, fatigue, and edema on physical, social, and emotional functions (scored 0 to 100). The median KCCQ score was 92, and 25% had KCCQ scores <75. Compared with cystatin C‑based estimated glomerular filtration rate >50 mL·min·1.73 m(2) (reference), estimated glomerular filtration rate 40 to 50, 30 to 40, and <30 were independently associated with lower KCCQ scores (<75); adjusted odds ratios and (95% CI): 1.38 (1.06-1.78), 1.39 (1.09-1.82), and 2.15 (1.54-3.00), respectively. Lower hemoglobin (Hb) levels also had independent associations with KCCQ <75: Hb >14 g/dL (reference), Hb 13 to 14 g/dL (1.03; 0.76-1.40), Hb 12 to 13 g/dL (1.41; 1.04-1.91), Hb 11 to 12 g/dL (1.56; 1.12-2.16); and Hb <1 g/dL (1.65; 1.15-2.37)., Conclusion: CKD patients without diagnosed HF have a substantial burden of symptoms characteristic of HF, particularly among those with lower estimated glomerular filtration rate and hemoglobin levels., (Published by Elsevier Inc.)
Published: 2011
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27. Resistin gene variation is associated with systemic inflammation but not plasma adipokine levels, metabolic syndrome or coronary atherosclerosis in nondiabetic Caucasians.

Author: Qasim AN, Metkus TS, Tadesse M, Lehrke M, Restine S, Wolfe ML, Hannenhalli S, Cappola T, Rader DJ, and Reilly MP
Subjects: Adipokines blood, Adiposity genetics, Adult, Biomarkers blood, Coronary Artery Disease blood, Coronary Artery Disease complications, Coronary Artery Disease genetics, Cytokines blood, Female, Gene Frequency, Haplotypes, Humans, Inflammation blood, Inflammation complications, Inflammation Mediators blood, Linkage Disequilibrium, Male, Metabolic Syndrome blood, Metabolic Syndrome complications, Metabolic Syndrome genetics, Middle Aged, Polymorphism, Single Nucleotide, White People, Genetic Variation, Inflammation genetics, Resistin genetics
Abstract: Objective: Resistin causes insulin resistance and diabetes in mice whereas in humans it is linked to inflammation and atherosclerosis. Few human genetic studies of resistin in inflammation and atherosclerosis have been performed. We hypothesized that the -420C>G putative gain-of-function resistin variant would be associated with inflammatory markers and atherosclerosis but not with metabolic syndrome or adipokines in humans., Design and Methods: We examined the association of three resistin polymorphisms, -852A>G, -420C>G and +157C>T, and related haplotypes with plasma resistin, cytokines, C-reactive protein (CRP), adipokines, plasma lipoproteins, metabolic syndrome and coronary artery calcification (CAC) in nondiabetic Caucasians (n = 851)., Results: Resistin levels were higher, dose-dependently, with the -420G allele (CC 5.9 +/- 2.7 ng/ml, GC 6.5 +/- 4.0 ng/ml and GG 7.2 +/- 4.8 ng/ml, trend P = 0.04) after age and gender adjustment [fold higher for GC + GG vs. CC; 1.07 (1.00-1.15), P < 0.05)]. The -852A>G single nucleotide polymorphism (SNP) was associated with higher soluble tumour necrosis factor-receptor 2 (sol-TNFR2) levels in fully adjusted models [1.06 (95% CI 1.01-1.11), P = 0.01)]. The estimated resistin haplotype (GGT) was associated with sol-TNFR2 (P = 0.04) and the AGT haplotype was related to CRP (P = 0.04) in the fully adjusted models. Resistin SNPs and haplotypes were not associated with body mass index (BMI), fasting glucose, insulin resistance, metabolic syndrome, adipokines or CAC scores., Conclusions: Despite modest associations with plasma resistin and inflammatory biomarkers, resistin 5' variants were not associated with metabolic parameters or coronary calcification. This suggests that resistin is an inflammatory cytokine in humans but has little influence on adiposity, metabolic syndrome or atherosclerosis.
Published: 2009
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28. GATA and Nkx factors synergistically regulate tissue-specific gene expression and development in vivo.

Author: Zhang Y, Rath N, Hannenhalli S, Wang Z, Cappola T, Kimura S, Atochina-Vasserman E, Lu MM, Beers MF, and Morrisey EE
Subjects: Alleles, Animals, Binding Sites, Cell Differentiation, Embryo, Mammalian cytology, Epithelium embryology, GATA6 Transcription Factor, Heterozygote, In Situ Hybridization, Lung embryology, Lung metabolism, Lung ultrastructure, Mesoderm cytology, Mesoderm metabolism, Mice, Mice, Inbred C57BL, Mice, Transgenic, Mutation, NIH 3T3 Cells, Nuclear Proteins, Oligonucleotide Array Sequence Analysis, Phospholipids analysis, Promoter Regions, Genetic, Thyroid Nuclear Factor 1, Transcription Factors genetics, Transfection, Gene Expression Regulation, Developmental, Transcription Factors metabolism
Abstract: In vitro studies have suggested that members of the GATA and Nkx transcription factor families physically interact, and synergistically activate pulmonary epithelial- and cardiac-gene promoters. However, the relevance of this synergy has not been demonstrated in vivo. We show that Gata6-Titf1 (Gata6-Nkx2.1) double heterozygous (G6-Nkx DH) embryos and mice have severe defects in pulmonary epithelial differentiation and distal airway development, as well as reduced phospholipid production. The defects in G6-Nkx DH embryos and mice are similar to those observed in human neonates with respiratory distress syndromes, including bronchopulmonary dysplasia, and differential gene expression analysis reveals essential developmental pathways requiring synergistic regulation by both Gata6 and Titf1 (Nkx2.1). These studies indicate that Gata6 and Nkx2.1 act in a synergistic manner to direct pulmonary epithelial differentiation and development in vivo, providing direct evidence that interactions between these two transcription factor families are crucial for the development of the tissues in which they are co-expressed.
Published: 2007
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29. Endomyocardial biopsy plays a role in diagnosing patients with unexplained cardiomyopathy.

Author: Ardehali H, Qasim A, Cappola T, Howard D, Hruban R, Hare JM, Baughman KL, and Kasper EK
Subjects: Amyloidosis pathology, Cardiomyopathies classification, Cardiomyopathies etiology, Chi-Square Distribution, Humans, Myocarditis pathology, Sensitivity and Specificity, Biopsy, Cardiomyopathies pathology, Endocardium pathology
Abstract: Background: The etiology of cardiomyopathy is usually inferred from clinical information and preliminary laboratory studies. Patients with unexplained cardiomyopathy may be referred for endomyocardial biopsy (EMBx). It is unknown whether pathological information obtained from EMBx is beneficial or alters the diagnosis established clinically. This study was undertaken to evaluate the utility of EMBx in confirming or excluding a clinically suspected diagnosis., Methods: We evaluated 845 patients with initially unexplained cardiomyopathy who underwent EMBx between 1982 and 1997 at The Johns Hopkins Hospital. For each patient, an initial clinical diagnosis, an EMBx diagnosis, and a final diagnosis prior to discharge based on all available data were established., Results: The final diagnosis differed from the initial clinical diagnosis in 264 (31%) of these patients; EMBx made the diagnosis in 196 (75%) of these cases. Initial diagnoses most frequently altered were myocarditis (34%) and idiopathic cardiomyopathy (25%). Initial diagnoses least likely to be altered were those in which biopsy was used to confirm or grade a previously documented illness, such as hemochromatosis (11%), amyloidosis (18%), or cardiomyopathy secondary to doxorubicin toxicity (0%). EMBx was more sensitive than clinical diagnosis in detecting myocarditis and amyloidosis, and proved to be very specific in detecting ischemic cardiomyopathy, myocarditis, amyloidosis, and hemochromatosis., Conclusions: In patients with unexplained cardiomyopathy after a standard evaluation, the clinical assessment of the etiology is inaccurate in 31% of patients. EMBx establishes the final diagnosis in 75% of these patients with a high degree of specificity.
Published: 2004
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29 results on '"Cappola, T"'

1. A pharmacogenetic investigation of intravenous furosemide in decompensated heart failure: a meta-analysis of three clinical trials

2. Baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF)

3. Treatment of Anemia with Darbepoetin Alfa in Systolic Heart Failure

4. CYP3A4 genotype is associated with sildenafil concentrations in patients with heart failure with preserved ejection fraction

5. Shared genetic etiology of peripartum and dilated cardiomyopathies

6. A pharmacogenetic investigation of intravenous furosemide in decompensated heart failure: a meta-analysis of three clinical trials

7. Gene-centric meta-analyses of 108 912 individuals confirm known body mass index loci and reveal three novel signals

8. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

9. CYP3A4 genotype is associated with sildenafil concentrations in patients with heart failure with preserved ejection fraction

10. Risk Prediction in Chronic Heart Failure

11. Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID): a phase 2 trial of intracoronary gene therapy of sarcoplasmic reticulum Ca2+-ATPase in patients with advanced heart failure.

12. Allopurinol improves myocardial efficiency in patients with idiopathic dilated cardiomyopathy.

13. Shared Genetic Predisposition in Peripartum and Dilated Cardiomyopathies.

14. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

15. Integrated landscape of cardiac metabolism in end-stage human nonischemic dilated cardiomyopathy.

16. Genomic Context Differs Between Human Dilated Cardiomyopathy and Hypertrophic Cardiomyopathy.

17. Clinical and Proteomic Correlates of Plasma ACE2 (Angiotensin-Converting Enzyme 2) in Human Heart Failure.

18. Clinical Phenogroups in Heart Failure With Preserved Ejection Fraction: Detailed Phenotypes, Prognosis, and Response to Spironolactone.

19. Antisense regulation of atrial natriuretic peptide expression.

20. Pathologic gene network rewiring implicates PPP1R3A as a central regulator in pressure overload heart failure.

21. Genomic Risk Stratification Predicts All-Cause Mortality After Cardiac Catheterization.

22. Associations of Conventional Echocardiographic Measures with Incident Heart Failure and Mortality: The Chronic Renal Insufficiency Cohort.

23. Causal Assessment of Serum Urate Levels in Cardiometabolic Diseases Through a Mendelian Randomization Study.

24. Systems Genomics Identifies a Key Role for Hypocretin/Orexin Receptor-2 in Human Heart Failure.

25. Response to letter regarding article, "Heart failure with recovered ejection fraction: clinical description, biomarkers, and outcomes".

26. Symptoms characteristic of heart failure among CKD patients without diagnosed heart failure.

27. Resistin gene variation is associated with systemic inflammation but not plasma adipokine levels, metabolic syndrome or coronary atherosclerosis in nondiabetic Caucasians.

28. GATA and Nkx factors synergistically regulate tissue-specific gene expression and development in vivo.

29. Endomyocardial biopsy plays a role in diagnosing patients with unexplained cardiomyopathy.

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