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2. Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Author

Maggioni, AP, Greene, SJ, Fonarow, GC, Bohm, M, Zannad, F, Solomon, SD, Lewis, EF, Baschiera, F, Hua, TA, Gimpelewicz, CR, Lesogor, A, Gheorghiade, M, Ramos, S, Luna, A, Miriuka, S, Diez, M, Perna, E, Luquez, H, Pinna, JG, Castagnino, J, Alvarenga, P, Ibanez, J, Blumberg, ES, Dizeo, C, Guerrero, RA, Schygiel, P, Milesi, R, Sosa, C, Hominal, M, Marquez, LL, Poy, C, Hasbani, E, Vico, M, Fernandez, A, Vita, N, Vanhaecke, J, De Keulenaer, G, Striekwold, H, Vervoort, G, Vrolix, M, Henry, P, Dendale, P, Smolders, W, Marechal, P, Vandekerckhove, H, Oliveira, M, Neuenschwande, F, Reis, G, Saraiva, J, Bodanese, L, Canesin, M, Greco, O, Bassan, R, Marino, RL, Giannetti, N, Moe, G, Sussex, B, Sheppard, R, Huynh, T, Stewart, R, Haddad, H, Echeverria, L, Quintero, A, Torres, A, Jaramillo, M, Lopez, M, Mendoza, F, Florez, N, Cotes, C, Garcia, M, Belohlavek, J, Hradec, J, Peterka, M, Gregor, P, Monhart, Z, Jansky, P, Kettner, J, Reichert, P, Spinar, J, Brabec, T, Hutyra, M, Solar, M, Pietila, M, Nyman, K, Pajari, R, Cohen, A, Galinier, M, Gosse, P, Livarek, B, Neuder, Y, Jourdain, P, Picard, F, Isnard, R, Hoppe, U, Kaeaeb, S, Rosocha, S, Prondzinsky, R, Felix, S, Duengen, H-D, and Figulla, H-R

Subjects
Heart Disease, Clinical Research, Clinical Trials and Supportive Activities, Diabetes, Cardiovascular, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Metabolic and endocrine, Administration, Oral, Amides, Cardiotonic Agents, Death, Sudden, Cardiac, Diabetic Cardiomyopathies, Double-Blind Method, Female, Fumarates, Heart Failure, Hospitalization, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Prospective Studies, Renin, Treatment Outcome, Aliskiren, Outcomes, Post-discharge, ASTRONAUT Investigators and Coordinators, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Cardiovascular System & Hematology
Abstract

AimsThe objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM).Methods and resultsASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction).ConclusionThis pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without DM.

Published
2013

6. 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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10. Towards better definition, quantification and treatment of fibrosis in heart failure. A scientific roadmap by the Committee of Translational Research of the Heart Failure Association (HFA) of the European Society of Cardiology

Author

de Boer, R.A. De Keulenaer, G. Bauersachs, J. Brutsaert, D. Cleland, J.G. Diez, J. Du, X.-J. Ford, P. Heinzel, F.R. Lipson, K.E. McDonagh, T. Lopez-Andres, N. Lunde, I.G. Lyon, A.R. Pollesello, P. Prasad, S.K. Tocchetti, C.G. Mayr, M. Sluijter, J.P.G. Thum, T. Tschöpe, C. Zannad, F. Zimmermann, W.-H. Ruschitzka, F. Filippatos, G. Lindsey, M.L. Maack, C. Heymans, S.

Abstract

Fibrosis is a pivotal player in heart failure development and progression. Measurements of (markers of) fibrosis in tissue and blood may help to diagnose and risk stratify patients with heart failure, and its treatment may be effective in preventing heart failure and its progression. A lack of pathophysiological insights and uniform definitions has hampered the research in fibrosis and heart failure. The Translational Research Committee of the Heart Failure Association discussed several aspects of fibrosis in their workshop. Early insidious perturbations such as subclinical hypertension or inflammation may trigger first fibrotic events, while more dramatic triggers such as myocardial infarction. and myocarditis give rise to full blown scar formation and ongoing fibrosis in diseased hearts. Aging itself is also associated with a cardiac phenotype that includes fibrosis. Fibrosis is an extremely heterogeneous phenomenon, as several stages of the fibrotic process exist, each with different fibrosis subtypes and a different composition of various cells and proteins — resulting in a very complex pathophysiology. As a result, detection of fibrosis, e.g. using current cardiac imaging modalities or plasma biomarkers, will detect only specific subforms of fibrosis, but cannot capture all aspects of the complex fibrotic process. Furthermore, several anti-fibrotic therapies are under investigation, but such therapies generally target aspecific aspects of the fibrotic process and suffer from a lack of precision. This review discusses the mechanisms and the caveats and proposes a roadmap for future research. © 2019 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Published
2019

11. Heart failure and diabetes: Metabolic alterations and therapeutic interventions: A state-of-The-Art review from the Translational Research Committee of the Heart Failure Association-European Society of Cardiology

Author

Maack, C. Lehrke, M. Backs, J. Heinzel, F.R. Hulot, J.-S. Marx, N. Paulus, W.J. Rossignol, P. Taegtmeyer, H. Bauersachs, J. Bayes-Genis, A. Brutsaert, D. Bugger, H. Clarke, K. Cosentino, F. De Keulenaer, G. Cas, A.D. González, A. Huelsmann, M. Iaccarino, G. Lunde, I.G. Lyon, A.R. Pollesello, P. Rena, G. Riksen, N.P. Rosano, G. Staels, B. Van Laake, L.W. Wanner, C. Farmakis, D. Filippatos, G. Ruschitzka, F. Seferovic, P. De Boer, R.A. Heymans, S.

Published
2018

12. 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. 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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

13. Eplerenone in patients with systolic heart failure and mild symptoms

Author

Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, Vincent J, Pocock SJ, Pitt B, Drexler H, McMurray J, Remme WJ, Cornel JH, Hildebrandt P, Hradec J, Mareev V, Reddy KS, Sindone A, Martinez F, Alonso Garcia A, Wilhelmsen L, Dargie HJ, Tavazzi L, Pocock S, Leizorovic A, Collier T, Nul DR, Serra JL, Thierer JM, Cross DB, Sindone AP, Singh BB, Boreux JL, Charlier FP, Dendale P, De Keulenaer G, Marchandise B, Marechal P, Marenne F, Mieghem WV, Van Dorpe AC, Vanhaecke J, Arnold JM, Dion D, Huynh T, Kouz SM, Lepage S, McKelvie RS, O'Meara E, Proulx G, Sauve C, Aschermann M, Brecka D, Filipovsky J, Groch L, Jerabek O, Jokl I, Linkova H, Motovska Z, Munz J, Penicka M, Rucka D, Mid JS, Spacek R, Spinar J, Stipal R, Vojacek J, Attali P, Bonneau A, Bousser JP, Dutoit L, Funck F, Galinier MP, Gibelin P, Hautefeuille BD, Hittinger L, Jobic Y, Jourdain P, Komajda M, Maupas E, Olive T, Philias A, Roul G, Rouleau F, Trochu JN, Boehm M, Bruch L, Engelhardt H, Erbs S, Foerster A, Franz N, Hambrecht R, Heuer H, Krueger U, Landmesser U, Leischik R, Mitrovic V, Moehlenkamp S, Monti J, Mueller Ehmsen J, Oezcelik C, Philipp S, Pieske B, Roehnisch JU, Schunkert H, Schwinger R, Wachter R, Willenbrock R, Winkelmann BR, Winkler R, Wollert KC, Adamopoulos S, Kalikazaros I, Karavidas A, Karvounis H, Kremastinos D, Manolis AJ, Nanas I, Sotirellos K, Vasiliadis K, Zaboulis C, Lee S, Yu CM, Czibok C, Édes I, Forster T, Preda I, Simon K, Takacs J, Zámolyi K, Bhagavatula KS, Chockalingam K, Desai N, Iyengar SS, Jayadev SM, Mullasari AS, Sathe SP, Sinha N, Vadagenalli PS, Wander GS, McDonald KM, Nash P, Vaughan CJ, Agostoni P, Ambrosio GB, Bittolo Bon G, Boffa G, Cacciavillani L, Capucci A, Chiariello M, Cirrincione V, Gensini GF, Masini F, Modena MG, Monte I, Rosano GM, Senni M, Sinagra G, Tamburino C, Terrosu P, Villani GQ, Volterrani M, Chae SC, Ha CW, Ha JW, Shin JH, Bayram Llamas E, Calvillo JC, Cruz Diaz A, Delgado Leal L, Estrada Gomez MM, Kosturakis D, Petersen Aranguren F, Velasco Sanchez RG, Daniëls MC, Dirkali A, Dunselman PH, de Kluiver EP, Kragten JA, Lok DJ, Maas AH, Michels HR, Nicastia DM, Stoel I, de Swart JB, Thijssen HJ, Van Kempen LH, Voors AA, Willems FF, Dluzniewski M, Gaciong Z, Kawecka Jaszcz K, Jozwa R, Korewicki J, Krzeminska Pakula M, Kurowski M, Ogorek M, Pempera M, Rynkiewicz A, Ujda M, Wierzchowiecki M, Abreu Á, Andrade A, Carrageta M, Fonseca C, Franco F, Gil VM, Lousada N, Mendonca C, Moreira I, Padua FP, Providência L, Cardoso JC, Trabulo M, Aroutyunov GP, Gindin K, Karpov YB, Kostenko VA, Nikitin YP, Obraztsova GI, Shilkina NP, Shlyakhto EV, Skvortsov A, Ding ZP, Yeo DP, Ambrovicova V, Gaspar L, Goncalvesova E, Kycina P, Litvinova J, Mikes Z, Murin J, Poliacik P, Uhliar R, Lloyd EA, Marx D, Naidoo DP, Prozesky HW, Sliwa Hahnle K, Theron H, Anguita M, De Teresa E, Galve E, Juanatey JR, Orbe PM, Vida M, Ahremark U, Andersson B, Axelsson U, Berglund S, Boman K, Dahlstrom U, Fu M, Holm Orndahl L, Johansson A, Lindgren M, Nemeczek C, Prantare H, Roussine V, Stehn G, Stenberg A, Vasko P, Bazylevych A, Dyadyk OI, Dzyak GV, Girina OM, Ignatenko GA, Kononenko LG, Kubyshkin VF, Kuryata OV, Parkhomenko AN, Perepelytsya MV, Pertseva TO, Popik GS, Rishko MV, Sakharchuk II, Tseluyko VI, Tykhonova SA, Vizir V, Voronkov LG, Al Khaja N, Almahmeed WA, Bazargani N, Adgey AA, Al Mohammad A, Banerjee P, Barlow M, Bridges AB, Brooks N, Connolly EC, Denvir MA, Egdell RM, Kardos A, Keeling PJ, Khokhar AA, Senior R, Williams SG, Anand IS, Anderson JL, Berk MR, Bertolet BD, Bisognano JD, Blonder RD, Breburda CS, Canaday DB, Capodilupo RC, Choiunard MD, Colucci WS, Dahiya RJ, Dunlap SH, Essandoh LK, Flores AR, Henderson DA, Herzog WR Jr, Katz RJ, Kosinski EJ, Labin IN, Lally FL, Lash JA, McGrew FA 3rd, Mohiuddin SM, Moraes D, Murali SC, Nallasivan M, Philbin E, Prabhu S, Primack DS, Ramani R, Rawitscher D, Sangrigoli R, Schamalfuss CM, Stoletniy L, Strong MH, Thadani U, Treasure CB 2nd, Vicari RM, Vogel CD, Wlsh MN, Wencker D, Wilson SA, Winkel E, Wiseman AH, Zoiopoulos LY, Mancebo JR, Mendoza I, Waich S.T., PERRONE FILARDI, PASQUALE, Zannad, F, Mcmurray, Jj, Krum, H, van Veldhuisen, Dj, Swedberg, K, Shi, H, Vincent, J, Pocock, Sj, Pitt, B, Drexler, H, Mcmurray, J, Remme, Wj, Cornel, Jh, Hildebrandt, P, Hradec, J, Mareev, V, Reddy, K, Sindone, A, Martinez, F, Alonso Garcia, A, Wilhelmsen, L, Dargie, Hj, Tavazzi, L, Pocock, S, Leizorovic, A, Collier, T, Nul, Dr, Serra, Jl, Thierer, Jm, Cross, Db, Sindone, Ap, Singh, Bb, Boreux, Jl, Charlier, Fp, Dendale, P, De Keulenaer, G, Marchandise, B, Marechal, P, Marenne, F, Mieghem, Wv, Van Dorpe, Ac, Vanhaecke, J, Arnold, Jm, Dion, D, Huynh, T, Kouz, Sm, Lepage, S, Mckelvie, R, O'Meara, E, Proulx, G, Sauve, C, Aschermann, M, Brecka, D, Filipovsky, J, Groch, L, Jerabek, O, Jokl, I, Linkova, H, Motovska, Z, Munz, J, Penicka, M, Rucka, D, Mid, J, Spacek, R, Spinar, J, Stipal, R, Vojacek, J, Attali, P, Bonneau, A, Bousser, Jp, Dutoit, L, Funck, F, Galinier, Mp, Gibelin, P, Hautefeuille, Bd, Hittinger, L, Jobic, Y, Jourdain, P, Komajda, M, Maupas, E, Olive, T, Philias, A, Roul, G, Rouleau, F, Trochu, Jn, Boehm, M, Bruch, L, Engelhardt, H, Erbs, S, Foerster, A, Franz, N, Hambrecht, R, Heuer, H, Krueger, U, Landmesser, U, Leischik, R, Mitrovic, V, Moehlenkamp, S, Monti, J, Mueller Ehmsen, J, Oezcelik, C, Philipp, S, Pieske, B, Roehnisch, Ju, Schunkert, H, Schwinger, R, Wachter, R, Willenbrock, R, Winkelmann, Br, Winkler, R, Wollert, Kc, Adamopoulos, S, Kalikazaros, I, Karavidas, A, Karvounis, H, Kremastinos, D, Manolis, Aj, Nanas, I, Sotirellos, K, Vasiliadis, K, Zaboulis, C, Lee, S, Yu, Cm, Czibok, C, Édes, I, Forster, T, Preda, I, Simon, K, Takacs, J, Zámolyi, K, Bhagavatula, K, Chockalingam, K, Desai, N, Iyengar, S, Jayadev, Sm, Mullasari, A, Sathe, Sp, Sinha, N, Vadagenalli, P, Wander, G, Mcdonald, Km, Nash, P, Vaughan, Cj, Agostoni, P, Ambrosio, Gb, Bittolo Bon, G, Boffa, G, Cacciavillani, L, Capucci, A, Chiariello, M, Cirrincione, V, Gensini, Gf, Masini, F, Modena, Mg, Monte, I, PERRONE FILARDI, Pasquale, Rosano, Gm, Senni, M, Sinagra, G, Tamburino, C, Terrosu, P, Villani, Gq, Volterrani, M, Chae, Sc, Ha, Cw, Ha, Jw, Shin, Jh, Bayram Llamas, E, Calvillo, Jc, Cruz Diaz, A, Delgado Leal, L, Estrada Gomez, Mm, Kosturakis, D, Petersen Aranguren, F, Velasco Sanchez, Rg, Daniëls, Mc, Dirkali, A, Dunselman, Ph, de Kluiver, Ep, Kragten, Ja, Lok, Dj, Maas, Ah, Michels, Hr, Nicastia, Dm, Stoel, I, de Swart, Jb, Thijssen, Hj, Van Kempen, Lh, Voors, Aa, Willems, Ff, Dluzniewski, M, Gaciong, Z, Kawecka Jaszcz, K, Jozwa, R, Korewicki, J, Krzeminska Pakula, M, Kurowski, M, Ogorek, M, Pempera, M, Rynkiewicz, A, Ujda, M, Wierzchowiecki, M, Abreu, Á, Andrade, A, Carrageta, M, Fonseca, C, Franco, F, Gil, Vm, Lousada, N, Mendonca, C, Moreira, I, Padua, Fp, Providência, L, Cardoso, Jc, Trabulo, M, Aroutyunov, Gp, Gindin, K, Karpov, Yb, Kostenko, Va, Nikitin, Yp, Obraztsova, Gi, Shilkina, Np, Shlyakhto, Ev, Skvortsov, A, Ding, Zp, Yeo, Dp, Ambrovicova, V, Gaspar, L, Goncalvesova, E, Kycina, P, Litvinova, J, Mikes, Z, Murin, J, Poliacik, P, Uhliar, R, Lloyd, Ea, Marx, D, Naidoo, Dp, Prozesky, Hw, Sliwa Hahnle, K, Theron, H, Anguita, M, De Teresa, E, Galve, E, Juanatey, Jr, Orbe, Pm, Vida, M, Ahremark, U, Andersson, B, Axelsson, U, Berglund, S, Boman, K, Dahlstrom, U, Fu, M, Holm Orndahl, L, Johansson, A, Lindgren, M, Nemeczek, C, Prantare, H, Roussine, V, Stehn, G, Stenberg, A, Vasko, P, Bazylevych, A, Dyadyk, Oi, Dzyak, Gv, Girina, Om, Ignatenko, Ga, Kononenko, Lg, Kubyshkin, Vf, Kuryata, Ov, Parkhomenko, An, Perepelytsya, Mv, Pertseva, To, Popik, G, Rishko, Mv, Sakharchuk, Ii, Tseluyko, Vi, Tykhonova, Sa, Vizir, V, Voronkov, Lg, Al Khaja, N, Almahmeed, Wa, Bazargani, N, Adgey, Aa, Al Mohammad, A, Banerjee, P, Barlow, M, Bridges, Ab, Brooks, N, Connolly, Ec, Denvir, Ma, Egdell, Rm, Kardos, A, Keeling, Pj, Khokhar, Aa, Senior, R, Williams, Sg, Anand, I, Anderson, Jl, Berk, Mr, Bertolet, Bd, Bisognano, Jd, Blonder, Rd, Breburda, C, Canaday, Db, Capodilupo, Rc, Choiunard, Md, Colucci, W, Dahiya, Rj, Dunlap, Sh, Essandoh, Lk, Flores, Ar, Henderson, Da, Herzog WR, Jr, Katz, Rj, Kosinski, Ej, Labin, In, Lally, Fl, Lash, Ja, McGrew FA, 3rd, Mohiuddin, Sm, Moraes, D, Murali, Sc, Nallasivan, M, Philbin, E, Prabhu, S, Primack, D, Ramani, R, Rawitscher, D, Sangrigoli, R, Schamalfuss, Cm, Stoletniy, L, Strong, Mh, Thadani, U, Treasure CB, 2nd, Vicari, Rm, Vogel, Cd, Wlsh, Mn, Wencker, D, Wilson, Sa, Winkel, E, Wiseman, Ah, Zoiopoulos, Ly, Mancebo, Jr, Mendoza, I, and Waich, S. T.

Published
2011

14. Effect of a telemonitoring-facilitated collaboration between general practitioner and heart failure clinic on mortality and rehospitalization rates in severe heart failure: the TEMA-HF 1 (TElemonitoring in the MAnagement of Heart Failure) study

Author

Paul, Dendale, De Keulenaer, G., Weytjens, Caroline, and Cardio-vascular diseases

Subjects
heart failure, telemonitoring, Mortality, Morbidity
Abstract

Chronic heart failure (CHF) patients are frequently rehospitalized within 6 months after an episode of fluid retention. Rehospitalizations are preventable, but this requires an extensive organization of the healthcare system. In this study, we tested whether intensive follow-up of patients through a telemonitoring-facilitated collaboration between general practitioners (GPs) and a heart failure clinic could reduce mortality and rehospitalization rate. One hunderd and sixty CHF patients [mean age 76 10 years, 104 males, mean left ventricular ejection fraction (LVEF) 35 15] were block randomized by sealed envelopes and assigned to 6 months of intense follow-up facilitated by telemonitoring (TM) or usual care (UC). The TM group measured body weight, blood pressure, and heart rate on a daily basis with electronic devices that transferred the data automatically to an online database. Email alerts were sent to the GP and heart failure clinic to intervene when pre-defined limits were exceeded. All-cause mortality was significantly lower in the TM group as compared with the UC group (5 vs. 17.5, P 0.01). The total number of follow-up days lost to hospitalization, dialysis, or death was significantly lower in the TM group as compared with the UC group (13 vs. 30 days, P 0.02). The number of hospitalizations for heart failure per patient showed a trend (0.24 vs. 0.42 hospitalizations/patient, P 0.06) in favour of TM. Telemonitoring-facilitated collaboration between GPs and a heart failure clinic reduces mortality and number of days lost to hospitalization, death, or dialysis in CHF patients. These findings need confirmation in a large trial.

Published
2012

15. Neuregulin attenuates right ventricular hypertrophy and dysfunction in an experimental model of pulmonary hypertension

Author

Ferreira, P. Mendes, Rocha, C. Maia, Adão, R., Silva, M., Mendes, M., Lourenço, A., Cerqueira, R., Chaves, P. Castro, De Keulenaer, G., Leite-Moreira, Adelino, Brás-Silva, Carmen, and Faculdade de Ciências da Nutrição e Alimentação

Subjects
Ciências da saúde [Ciências médicas e da saúde], Other medical sciences, Outras ciências médicas, Other medical sciences [Medical and Health sciences], Ciências da Saúde, Ciências da saúde, Health sciences, Health sciences, Health sciences [Medical and Health sciences], Outras ciências médicas [Ciências médicas e da saúde]
Abstract

[resumo] [abstract]

Published
2011

22. Poster session 3

Author

Nanka, O., primary, Krejci, E., additional, Pesevski, Z., additional, Sedmera, D., additional, Smart, N., additional, Rossdeutsch, A., additional, Dube, K. N., additional, Riegler, J., additional, Price, A. N., additional, Taylor, A., additional, Muthurangu, V., additional, Turner, M., additional, Lythgoe, M. F., additional, Riley, P. R., additional, Kryvorot, S., additional, Vladimirskaya, T., additional, Shved, I., additional, Schwarzl, M., additional, Seiler, S., additional, Huber, S., additional, Steendijk, P., additional, Maechler, H., additional, Truschnig-Wilders, M., additional, Pieske, B., additional, Post, H., additional, Caprio, C., additional, Baldini, A., additional, Chiavacci, E., additional, Dolfi, L., additional, Verduci, L., additional, Meghini, F., additional, Cremisi, F., additional, Pitto, L., additional, Kuan, T.-C., additional, Chen, M.-C., additional, Yang, T.-H., additional, Wu, W.-T., additional, Lin, C. S., additional, Rai, H., additional, Kumar, S., additional, Sharma, A. K., additional, Mastana, S., additional, Kapoor, A., additional, Pandey, C. M., additional, Agrawal, S., additional, Sinha, N., additional, Orlowska-Baranowska, E. H., additional, Placha, G., additional, Gora, J., additional, Baranowski, R., additional, Abramczuk, E., additional, Hryniewiecki, T., additional, Gaciong, Z., additional, Verschuren, J. J. W., additional, Wessels, J. A. M., additional, Trompet, S., additional, Stott, D. J., additional, Sattar, N., additional, Buckley, B., additional, Guchelaar, H. J., additional, Jukema, J. W., additional, Gharanei, M., additional, Hussain, A., additional, Mee, C. J., additional, Maddock, H. L., additional, Wijnen, W. J., additional, Van Den Oever, S., additional, Van Der Made, I., additional, Hiller, M., additional, Tijsen, A. J., additional, Pinto, Y. M., additional, Creemers, E. E., additional, Nikulina, S. U. Y., additional, Chernova, A., additional, Petry, A., additional, Rzymski, T., additional, Kracun, D., additional, Riess, F., additional, Pike, L., additional, Harris, A. L., additional, Gorlach, A., additional, Katare, R., additional, Oikawa, A., additional, Riu, F., additional, Beltrami, A. P., additional, Cesseli, D., additional, Emanueli, C., additional, Madeddu, P., additional, Zaglia, T., additional, Milan, G., additional, Franzoso, M., additional, Pesce, P., additional, Sarais, C., additional, Sandri, M., additional, Mongillo, M., additional, Butler, T. J., additional, Seymour, A.-M. L., additional, Ashford, D., additional, Jaffre, F., additional, Bussen, M., additional, Flohrschutz, I., additional, Martin, G. R., additional, Engelhardt, S., additional, Kararigas, G., additional, Nguyen, B. T., additional, Jarry, H., additional, Regitz-Zagrosek, V., additional, Van Bilsen, M., additional, Daniels, A., additional, Munts, C., additional, Janssen, B. J. A., additional, Van Der Vusse, G. J., additional, Van Nieuwenhoven, F. A., additional, Montalvo, C., additional, Villar, A. V., additional, Merino, D., additional, Garcia, R., additional, Llano, M., additional, Ares, M., additional, Hurle, M. A., additional, Nistal, J. F., additional, Dembinska-Kiec, A., additional, Beata Kiec-Wilk, B. K. W., additional, Anna Polus, A. P., additional, Urszula Czech, U. C., additional, Tatiana Konovaleva, T. K., additional, Gerd Schmitz, G. S., additional, Bertrand, L., additional, Balteau, M., additional, Timmermans, A., additional, Viollet, B., additional, Sakamoto, K., additional, Feron, O., additional, Horman, S., additional, Vanoverschelde, J. L., additional, Beauloye, C., additional, De Meester, C., additional, Martinez, E., additional, Martin, R., additional, Miana, M., additional, Jurado, R., additional, Gomez-Hurtado, N., additional, Bartolome, M. V., additional, San Roman, J. A., additional, Lahera, V., additional, Nieto, M. L., additional, Cachofeiro, V., additional, Rochais, F., additional, Sturny, R., additional, Mesbah, K., additional, Miquerol, L., additional, Kelly, R. G., additional, Messaoudi, S., additional, Gravez, B., additional, Tarjus, A., additional, Pelloux, V., additional, Samuel, J. L., additional, Delcayre, C., additional, Launay, J. M., additional, Clement, K., additional, Farman, N., additional, Jaisser, F., additional, Hadyanto, L., additional, Castellani, C., additional, Vescovo, G., additional, Ravara, B., additional, Tavano, R., additional, Pozzobon, M., additional, De Coppi, P., additional, Papini, E., additional, Vettor, R., additional, Thiene, G., additional, Angelini, A., additional, Meloni, M., additional, Caporali, A., additional, Cesselli, D., additional, Fortunato, O., additional, Avolio, E., additional, Schindler, R., additional, Simrick, S., additional, Brand, T., additional, Smart, N. S., additional, Herman, A., additional, Roura Ferrer, S., additional, Rodriguez Bago, J., additional, Soler-Botija, C., additional, Pujal, J. M., additional, Galvez-Monton, C., additional, Prat-Vidal, C., additional, Llucia-Valldeperas, A., additional, Blanco, J., additional, Bayes-Genis, A., additional, Foldes, G., additional, Maxime, M., additional, Ali, N. N., additional, Schneider, M. D., additional, Harding, S. E., additional, Reni, C., additional, Mangialardi, G., additional, De Pauw, A., additional, Sekkali, B., additional, Friart, A., additional, Ding, H., additional, Graffeuil, A., additional, Catalucci, D., additional, Balligand, J. L., additional, Azibani, F., additional, Tournoux, F., additional, Schlossarek, S., additional, Polidano, E., additional, Fazal, L., additional, Merval, R., additional, Carrier, L., additional, Chatziantoniou, C., additional, Buyandelger, B., additional, Linke, W., additional, Zou, P., additional, Kostin, S., additional, Ku, C., additional, Felkin, L., additional, Birks, E., additional, Barton, P., additional, Sattler, M., additional, Knoell, R., additional, Schroder, K., additional, Benkhoff, S., additional, Shimokawa, H., additional, Grisk, O., additional, Brandes, R. P., additional, Parepa, I. R., additional, Mazilu, L., additional, Suceveanu, A. I., additional, Suceveanu, A., additional, Rusali, L., additional, Cojocaru, L., additional, Matei, L., additional, Toringhibel, M., additional, Craiu, E., additional, Pires, A. L., additional, Pinho, M., additional, Pinho, S., additional, Sena, C., additional, Seica, R., additional, Leite-Moreira, A., additional, Dabroi, F., additional, Schiaffino, S., additional, Kiseleva, E., additional, Krukov, N., additional, Nikitin, O., additional, Ardatova, L., additional, Mourouzis, I., additional, Pantos, C., additional, Kokkinos, A. D., additional, Cokkinos, D. V., additional, Scoditti, E., additional, Massaro, M., additional, Carluccio, M. A., additional, Pellegrino, M., additional, Calabriso, N., additional, Gastaldelli, A., additional, Storelli, C., additional, De Caterina, R., additional, Lindner, D., additional, Zietsch, C., additional, Schultheiss, H.-P., additional, Tschope, C., additional, Westermann, D., additional, Everaert, B. R., additional, Nijenhuis, V. J., additional, Reith, F. C. M., additional, Hoymans, V. Y., additional, Timmermans, J. P., additional, Vrints, C. J., additional, Simova, I., additional, Mateev, H., additional, Katova, T., additional, Haralanov, L., additional, Dimitrov, N., additional, Mironov, N., additional, Golitsyn, S. P., additional, Sokolov, S. F., additional, Yuricheva, Y. U. A., additional, Maikov, E. B., additional, Shlevkov, N. B., additional, Rosenstraukh, L. V., additional, Chazov, E. I., additional, Radosinska, J., additional, Knezl, V., additional, Benova, T., additional, Slezak, J., additional, Urban, L., additional, Tribulova, N., additional, Virag, L., additional, Kristof, A., additional, Kohajda, Z. S., additional, Szel, T., additional, Husti, Z., additional, Baczko, I., additional, Jost, N., additional, Varro, A., additional, Sarusi, A., additional, Farkas, A. S., additional, Orosz, S. Z., additional, Forster, T., additional, Farkas, A., additional, Zakhrabova-Zwiauer, O. M., additional, Hardziyenka, M., additional, Nieuwland, R., additional, Tan, H. L., additional, Raaijmakers, A. J. A., additional, Bourgonje, V. J. A., additional, Kok, G. J. M., additional, Van Veen, A. A. B., additional, Anderson, M. E., additional, Vos, M. A., additional, Bierhuizen, M. F. A., additional, Benes, J., additional, Sebestova, B., additional, Ghouri, I. A., additional, Kemi, O. J., additional, Kelly, A., additional, Burton, F. L., additional, Smith, G. L., additional, Ozdemir, S., additional, Acsai, K., additional, Doisne, N., additional, Van Der Nagel, R., additional, Beekman, H. D. M., additional, Van Veen, T. A. B., additional, Sipido, K. R., additional, Antoons, G., additional, Harmer, S. C., additional, Mohal, J. S., additional, Kemp, D., additional, Tinker, A., additional, Beech, D., additional, Burley, D. S., additional, Cox, C. D., additional, Wann, K. T., additional, Baxter, G. F., additional, Wilders, R., additional, Verkerk, A., additional, Fragkiadaki, P., additional, Germanakis, G., additional, Tsarouchas, K., additional, Tsitsimpikou, C., additional, Tsardi, M., additional, George, D., additional, Tsatsakis, A., additional, Rodrigues, P., additional, Barros, C., additional, Najmi, A. K., additional, Khan, V., additional, Akhtar, M., additional, Pillai, K. K., additional, Mujeeb, M., additional, Aqil, M., additional, Bayliss, C. R., additional, Messer, A. E., additional, Leung, M.-C., additional, Ward, D., additional, Van Der Velden, J., additional, Poggesi, C., additional, Redwood, C. S., additional, Marston, S., additional, Vite, A., additional, Gandjbakhch, E., additional, Gary, F., additional, Fressart, V., additional, Leprince, P., additional, Fontaine, G., additional, Komajda, M., additional, Charron, P., additional, Villard, E., additional, Falcao-Pires, I., additional, Gavina, C., additional, Hamdani, N., additional, Stienen, G. J. M., additional, Niessens, H. W. M., additional, Leite-Moreira, A. F., additional, Paulus, W. J., additional, Memo, M., additional, Marston, S. B., additional, Vafiadaki, E., additional, Qian, J., additional, Arvanitis, D. A., additional, Sanoudou, D., additional, Kranias, E. G., additional, Elmstedt, N., additional, Lind, B., additional, Ferm-Widlund, K., additional, Westgren, M., additional, Brodin, L.-A., additional, Mansfield, C., additional, West, T., additional, Ferenczi, M., additional, Wijnker, P. J. M., additional, Foster, D. B., additional, Coulter, A., additional, Frazier, A., additional, Murphy, A. M., additional, Shah, M., additional, Sikkel, M. B., additional, Desplantez, T., additional, Collins, T. P., additional, O' Gara, P., additional, Lyon, A. R., additional, Macleod, K. T., additional, Ottesen, A. H., additional, Louch, W. E., additional, Carlson, C., additional, Landsverk, O. J. B., additional, Stridsberg, M., additional, Sjaastad, I., additional, Oie, E., additional, Omland, T., additional, Christensen, G., additional, Rosjo, H., additional, Cartledge, J., additional, Clark, L. A., additional, Ibrahim, M., additional, Siedlecka, U., additional, Navaratnarajah, M., additional, Yacoub, M. H., additional, Camelliti, P., additional, Terracciano, C. M., additional, Chester, A., additional, Gonzalez-Tendero, A., additional, Torre, I., additional, Garcia-Garcia, F., additional, Dopazo, J., additional, Gratacos, E., additional, Taylor, D., additional, Bhandari, S., additional, Seymour, A.-M., additional, Fliegner, D., additional, Jost, J., additional, Bugger, H., additional, Ventura-Clapier, R., additional, Carpi, A., additional, Campesan, M., additional, Canton, M., additional, Menabo, R., additional, Pelicci, P. G., additional, Giorgio, M., additional, Di Lisa, F., additional, Hancock, M., additional, Venturini, A., additional, Al-Shanti, N., additional, Stewart, C., additional, Ascione, R., additional, Angelini, G., additional, Suleiman, M.-S., additional, Kravchuk, E., additional, Grineva, E., additional, Galagudza, M., additional, Kostareva, A., additional, Bairamov, A., additional, Krychtiuk, K. A., additional, Watzke, L., additional, Kaun, C., additional, Demyanets, S., additional, Pisoni, J., additional, Kastl, S. P., additional, Huber, K., additional, Maurer, G., additional, Wojta, J., additional, Speidl, W. S., additional, Varga, Z. V., additional, Farago, N., additional, Zvara, A., additional, Kocsis, G. F., additional, Pipicz, M., additional, Csonka, C., additional, Csont, T., additional, Puskas, G. L., additional, Ferdinandy, P., additional, Klevstigova, M., additional, Silhavy, J., additional, Manakov, D., additional, Papousek, F., additional, Novotny, J., additional, Pravenec, M., additional, Kolar, F., additional, Novakova, O., additional, Novak, F., additional, Neckar, J., additional, Barallobre-Barreiro, J., additional, Didangelos, A., additional, Yin, X., additional, Fernandez-Caggiano, M., additional, Drozdov, I., additional, Willeit, P., additional, Domenech, N., additional, Mayr, M., additional, Lemoine, S., additional, Allouche, S., additional, Coulbault, L., additional, Galera, P., additional, Gerard, J. L., additional, Hanouz, J. L., additional, Suveren, E., additional, Whiteman, M., additional, Studneva, I. M., additional, Pisarenko, O., additional, Shulzhenko, V., additional, Serebryakova, L., additional, Tskitishvili, O., additional, Timoshin, A., additional, Fauconnier, J., additional, Meli, A. C., additional, Thireau, J., additional, Roberge, S., additional, Lompre, A. M., additional, Jacotot, E., additional, Marks, A. M., additional, Lacampagne, A., additional, Dietel, B., additional, Altendorf, R., additional, Daniel, W. G., additional, Kollmar, R., additional, Garlichs, C. D., additional, Parente, V., additional, Balasso, S., additional, Pompilio, G., additional, Colombo, G., additional, Milano, G., additional, Squadroni, L., additional, Cotelli, F., additional, Pozzoli, O., additional, Capogrossi, M. C., additional, Ajiro, Y., additional, Saegusa, N., additional, Iwade, K., additional, Giles, W. R., additional, Stafforini, D. M., additional, Spitzer, K. W., additional, Sirohi, R., additional, Candilio, L., additional, Babu, G., additional, Roberts, N., additional, Lawrence, D., additional, Sheikh, A., additional, Kolvekar, S., additional, Yap, J., additional, Hausenloy, D. J., additional, Yellon, D. M., additional, Aslam, M., additional, Rohrbach, S., additional, Schlueter, K.-D., additional, Piper, H. M., additional, Noll, T., additional, Guenduez, D., additional, Malinova, L., additional, Ryabukho, V. P., additional, Lyakin, D. V., additional, Denisova, T. P., additional, Montoro-Garcia, S., additional, Shantsila, E., additional, Lip, G. Y. H., additional, Kalaska, B., additional, Sokolowska, E., additional, Kaminski, K., additional, Szczubialka, K., additional, Kramkowski, K., additional, Mogielnicki, A., additional, Nowakowska, M., additional, Buczko, W., additional, Stancheva, N., additional, Mekenyan, E., additional, Gospodinov, K., additional, Tisheva, S., additional, Darago, A., additional, Rutkai, I., additional, Kalasz, J., additional, Czikora, A., additional, Orosz, P., additional, Bjornson, H. D., additional, Edes, I., additional, Papp, Z., additional, Toth, A., additional, Riches, K., additional, Warburton, P., additional, O'regan, D. J., additional, Ball, S. G., additional, Turner, N. A., additional, Wood, I. C., additional, Porter, K. E., additional, Kogaki, S., additional, Ishida, H., additional, Nawa, N., additional, Takahashi, K., additional, Baden, H., additional, Ichimori, H., additional, Uchikawa, T., additional, Mihara, S., additional, Miura, K., additional, Ozono, K., additional, Lugano, R., additional, Padro, T., additional, Garcia-Arguinzonis, M., additional, Badimon, L., additional, Ferraro, F., additional, Viner, R., additional, Ho, J., additional, Cutler, D., additional, Matchkov, V., additional, Aalkjaer, C., additional, Krijnen, P. A. J., additional, Hahn, N. E., additional, Kholova, I., additional, Sipkens, J. A., additional, Van Alphen, F. P., additional, Simsek, S., additional, Schalkwijk, C. G., additional, Van Buul, J. D., additional, Van Hinsbergh, V. W. M., additional, Niessen, H. W. M., additional, Caro, C. G., additional, Seneviratne, A., additional, Monaco, C., additional, Hou, D., additional, Singh, J., additional, Gilson, P., additional, Burke, M. G., additional, Heraty, K. B., additional, Krams, R., additional, Coppola, G., additional, Albrecht, K., additional, Schgoer, W., additional, Wiedemann, D., additional, Bonaros, N., additional, Steger, C., additional, Theurl, M., additional, Stanzl, U., additional, Kirchmair, R., additional, Amadesi, S., additional, Spinetti, G., additional, Cangiano, E., additional, Valgimigli, M., additional, Miller, A. M., additional, Cardinali, A., additional, Vierlinger, K., additional, Pagano, G., additional, Liccardo, D., additional, Zincarelli, C., additional, Femminella, G. D., additional, Lymperopoulos, A., additional, De Lucia, C., additional, Koch, W. J., additional, Leosco, D., additional, Rengo, G., additional, Hinkel, R., additional, Husada, W., additional, Trenkwalder, T., additional, Di, Q., additional, Lee, S., additional, Petersen, B., additional, Bock-Marquette, I., additional, Niemann, H., additional, Di Maio, M., additional, Kupatt, C., additional, Nourian, M., additional, Yassin, Z., additional, Kelishadi, R., additional, Memarian, S. H., additional, Heidari, A., additional, Leuner, A., additional, Poitz, D. M., additional, Brunssen, C., additional, Ravens, U., additional, Strasser, R. H., additional, Morawietz, H., additional, Vogt, F., additional, Grahl, A., additional, Flege, C., additional, Marx, N., additional, Borinski, M., additional, De Geest, B., additional, Jacobs, F., additional, Muthuramu, I., additional, Gordts, S. C., additional, Van Craeyveld, E., additional, Herijgers, P., additional, Weinert, S., additional, Medunjanin, S., additional, Herold, J., additional, Schmeisser, A., additional, Braun-Dullaeus, R. C., additional, Wagner, A. H., additional, Moeller, K., additional, Adolph, O., additional, Schwarz, M., additional, Schwale, C., additional, Bruehl, C., additional, Nobiling, R., additional, Wieland, T., additional, Schneider, S. W., additional, Hecker, M., additional, Cross, A., additional, Strom, A., additional, Cole, J., additional, Goddard, M., additional, Hultgardh-Nilsson, A., additional, Nilsson, J., additional, Mauri, C., additional, Mitkovskaya, N. P., additional, Kurak, T. A., additional, Oganova, E. G., additional, Shkrebneva, E. I., additional, Kot, Z. H. N., additional, Statkevich, T. V., additional, Molica, F., additional, Burger, F., additional, Matter, C. M., additional, Thomas, A., additional, Staub, C., additional, Zimmer, A., additional, Cravatt, B., additional, Pacher, P., additional, Steffens, S., additional, Blanco, R., additional, Sarmiento, R., additional, Parisi, C., additional, Fandino, S., additional, Blanco, F., additional, Gigena, G., additional, Szarfer, J., additional, Rodriguez, A., additional, Garcia Escudero, A., additional, Riccitelli, M. A., additional, Wantha, S., additional, Simsekyilmaz, S., additional, Megens, R. T., additional, Van Zandvoort, M. A., additional, Liehn, E., additional, Zernecke, A., additional, Klee, D., additional, Weber, C., additional, Soehnlein, O., additional, Lima, L. M., additional, Carvalho, M. G., additional, Gomes, K. B., additional, Santos, I. R., additional, Sousa, M. O., additional, Morais, C. A. S., additional, Oliveira, S. H. V., additional, Gomes, I. F., additional, Brandao, F. C., additional, Lamego, M. R. A., additional, Fornai, L., additional, Kiss, A., additional, Giskes, F., additional, Eijkel, G., additional, Fedrigo, M., additional, Valente, M. L., additional, Heeren, R. M. A., additional, Grdinic, A., additional, Vojvodic, D., additional, Djukanovic, N., additional, Grdinic, A. G., additional, Obradovic, S., additional, Majstorovic, I., additional, Rusovic, S., additional, Vucinic, Z., additional, Tavciovski, D., additional, Ostojic, M., additional, Lai, S.-C., additional, Chen, M.-Y., additional, Wu, H.-T., additional, Gouweleeuw, L., additional, Oberdorf-Maass, S. U., additional, De Boer, R. A., additional, Van Gilst, W. H., additional, Maass, A. H., additional, Van Gelder, I. C., additional, Benard, L., additional, Li, C., additional, Warren, D., additional, Shanahan, C. M., additional, Zhang, Q. P., additional, Bye, A., additional, Vettukattil, R., additional, Aspenes, S. T., additional, Giskeodegaard, G., additional, Gribbestad, I. S., additional, Wisloff, U., additional, Bathen, T. F., additional, Cubedo, J., additional, Alonso, R., additional, Mata, P., additional, Ivic, I., additional, Vamos, Z., additional, Cseplo, P., additional, Kosa, D., additional, Torok, O., additional, Hamar, J., additional, Koller, A., additional, Norita, K., additional, De Noronha, S. V., additional, Sheppard, M. N., additional, Amat-Roldan, I., additional, Iruretagoiena, I., additional, Psilodimitrakopoulos, S., additional, Crispi, F., additional, Artigas, D., additional, Loza-Alvarez, P., additional, Harrison, J. C., additional, Smart, S. D., additional, Besely, E. H., additional, Kelly, J. R., additional, Yao, Y., additional, Sammut, I. A., additional, Hoepfner, M., additional, Kuzyniak, W., additional, Sekhosana, E., additional, Hoffmann, B., additional, Litwinski, C., additional, Pries, A., additional, Ermilov, E., additional, Fontoura, D., additional, Lourenco, A. P., additional, Vasques-Novoa, F., additional, Pinto, J. P., additional, Roncon-Albuquerque, R., additional, Oyeyipo, I. P., additional, Olatunji, L. A., additional, Usman, T. O., additional, Olatunji, V. A., additional, Bacova, B., additional, Viczenczova, C., additional, Dosenko, V., additional, Goncalvesova, E., additional, Vanrooyen, J., additional, Maulik, S. K., additional, Seth, S., additional, Dinda, A. K., additional, Jaiswal, A., additional, Mearini, G., additional, Khajetoorians, D., additional, Kraemer, E., additional, Gedicke-Hornung, C., additional, Precigout, G., additional, Eschenhagen, T., additional, Voit, T., additional, Garcia, L., additional, Lorain, S., additional, Mendes-Ferreira, P., additional, Maia-Rocha, C., additional, Adao, R., additional, Cerqueira, R. J., additional, Mendes, M. J., additional, Castro-Chaves, P., additional, De Keulenaer, G. W., additional, Bras-Silva, C., additional, Ruiter, G., additional, Wong, Y. Y., additional, Lubberink, M., additional, Knaapen, P., additional, Raijmakers, P., additional, Lammertsma, A. A., additional, Marcus, J. T., additional, Westerhof, N., additional, Van Der Laarse, W. J., additional, Vonk-Noordegraaf, A., additional, Steinbronn, N., additional, Koch, E., additional, Steiner, G., additional, Berezin, A., additional, Lisovaya, O. A., additional, Soldatova, A. M., additional, Kuznetcov, V. A., additional, Yenina, T. N., additional, Rychkov, A. Y. U., additional, Shebeko, P. V., additional, Altara, R., additional, Hessel, M. H. M., additional, Hermans, J. J. R., additional, Blankesteijn, W. M., additional, Berezina, T. A., additional, Seden, V., additional, Bonanad, C., additional, Nunez, J., additional, Navarro, D., additional, Chilet, M. F., additional, Sanchis, F., additional, Bodi, V., additional, Minana, G., additional, Chaustre, F., additional, Forteza, M. J., additional, Llacer, A., additional, Galasso, G., additional, Ferrara, N., additional, Akhmedov, A., additional, Klingenberg, R., additional, Brokopp, C., additional, Hof, D., additional, Zoller, S., additional, Corti, R., additional, Gay, S., additional, Von Eckardstein, A., additional, Hoerstrup, S. P., additional, Luescher, T. F., additional, Heijman, J., additional, Zaza, A., additional, Johnson, D. M., additional, Rudy, Y., additional, Peeters, R. L. M., additional, Volders, P. G. A., additional, Westra, R. L., additional, Fujita, S., additional, Okamoto, R., additional, Taniguchi, M., additional, Konishi, K., additional, Goto, I., additional, Sugimoto, K., additional, Nakamura, M., additional, Shiraki, K., additional, Buechler, C., additional, and Ito, M., additional

Published
2012
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31. Sistema Neuregulina1/ErbB: importância no controlo da função cardíaca

Author

Lopes-Conceição L, Dias-Neto M, Ap, Fontes-Sousa, Pedro Ferreira, Maia-Rocha C, Henriques-Coelho T, de Keulenaer G, Af, Leite Moreira, Brás-Silva C, and Faculdade de Medicina

Subjects
Ciências médicas e da saúde, Medical and Health sciences
Abstract

The family of Neuregulins (NRG), growth factors like epidermal growth factor, is known to induce growth and differentiation of epithelial, glial, neuronal, and skeletal muscle cells. This family comprises four members, being NRG1 the most largely studied, particularly at the cardiovascular level. The biological effects of NRG1 in the adult heart are mediated by the tyrosine kinase receptors ErbB. In the adult heart, NRG1 is expressed by cells of the endocardial endothelium and the cardiac microvascular endothelium, and the receptors ErbB2/ErbB4 are expressed by ventricular cardiomyocytes and are located in T-tubule system and intercalated disks in close proximity to the system components of excitation-contraction coupling. The importance of the NRG/ErbB signaling axis at the cardiovascular level became evident after discovering that patients treated with trastuzumab (inhibitory antibody against ErbB2, used in the treatment of breast cancer) can develop ventricular dysfunction and have higher risk of cardiomyopathy when co-administered with anthracyclines. Subsequent studies in vitro and in vivo have clarified the effects and the respective signaling pathways associated with the NRG/ErbB system in the adult heart. Some cardiovascular functions of the NRG1/ErbB system have been described at the vascular (stimulation of angiogenesis and ateroprotector effect) and myocardium level (negative inotropic effect) as well as effect on the survival, cell growth and organization of the cardiomyocytes (myofibrillar organization and cell-to-cell contact between cardiomyocytes). Furthermore, the interaction of this system with other neurohumoral mediators has been studied. Thus, there seems to be a physiological role in modulating the sympathovagal balance and an interaction with endothelin-1 signaling. All these effects result from the activation of different intracellular signaling cascades, as a consequence of the binding of NRG1 to ErbB receptors. Some cardiac signaling pathways identified until now include molecules such as MEK / Erk 1/2, phosphatidylinositol 3-kinase/ Akt, focal adhesion kinase, Gab (Grb-2-associated binder) family, vascular endothelial growth factor and NO production by endothelial nitric oxide synthase. Thus, the aim of this paper was to make an up-to-date review of existing information on NRG1/ErbB signaling axis, with particular focus on its cardiovascular effects.

32. Treatments targeting inotropy

Author

Dietmar J. Manstein, Jean-Luc Balligand, Joseph M. Metzger, Veli-Pekka Harjola, Christoph Maack, Frank Ruschitzka, Marco Metra, Stefan Chlopicki, Nazha Hamdani, Alexander Dietl, Denise Hilfiker-Kleiner, M. Birhan Yilmaz, Johannes Holzmeister, Alexander R. Lyon, Christian Mueller, Petar M. Seferovic, Stefan D. Anker, Johann Bauersachs, Gilles W. De Keulenaer, Giuseppe Limongelli, Alexandre Mebazaa, Dirk L. Brutsaert, Rodolphe Fischmeister, Lucie Carrier, Rudolf A. de Boer, Josep Masip, Burkert Pieske, John G.F. Cleland, Wolfram H. Zimmermann, Zoltán Papp, Frank R. Heinzel, Carlo G. Tocchetti, Piotr Ponikowski, Lars H. Lund, Stephane Heymans, Thomas Eschenhagen, Wolfgang A. Linke, Arsen D. Ristić, Hadi Skouri, Maack, Christoph, Eschenhagen, Thoma, Hamdani, Nazha, Heinzel, Frank R, Lyon, Alexander R, Manstein, Dietmar J, Metzger, Joseph, Papp, Zoltán, Tocchetti, Carlo G, Yilmaz, M Birhan, Anker, Stefan D, Balligand, Jean-Luc, Bauersachs, Johann, Brutsaert, Dirk, Carrier, Lucie, Chlopicki, Stefan, Cleland, John G, de Boer, Rudolf A, Dietl, Alexander, Fischmeister, Rodolphe, Harjola, Veli-Pekka, Heymans, Stephane, Hilfiker-Kleiner, Denise, Holzmeister, Johanne, de Keulenaer, Gille, Limongelli, Giuseppe, Linke, Wolfgang A, Lund, Lars H, Masip, Josep, Metra, Marco, Mueller, Christian, Pieske, Burkert, Ponikowski, Piotr, Ristic, Arsen, Ruschitzka, Frank, Seferovic, Petar M, Skouri, Hadi, Zimmermann, Wolfram H, Mebazaa, Alexandre, HUS Emergency Medicine and Services, University of Helsinki, Department of Diagnostics and Therapeutics, Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), RS: Carim - H02 Cardiomyopathy, RS: CARIM - R2.02 - Cardiomyopathy, Maack, C, Eschenhagen, T, Hamdani, N, Heinzel, Fr, Lyon, Ar, Manstein, Dj, Metzger, J, Papp, Z, Tocchetti, Cg, Yilmaz, Mb, Anker, Sd, Balligand, Jl, Bauersachs, J, Brutsaert, D, Carrier, L, Chlopicki, S, Cleland, Jg, de Boer, Ra, Dietl, A, Fischmeister, R, Harjola, Vp, Heymans, S, Hilfiker-Kleiner, D, Holzmeister, J, de Keulenaer, G, Limongelli, G, Linke, Wa, Lund, Lh, Masip, J, Metra, M, Mueller, C, Pieske, B, Ponikowski, P, Ristic, A, Ruschitzka, F, Seferovic, Pm, Skouri, H, Zimmermann, Wh, Mebazaa, A, UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique, and UCL - (SLuc) Service de médecine interne générale

Subjects
Inotrope, Acute decompensated heart failure, Phosphodiesterase Inhibitors, Swine, Levosimendan, 030204 cardiovascular system & hematology, Omecamtiv mecarbil, Contractility, Antioxidants, Placebos, 0302 clinical medicine, Catecholamines, Diastole, Dobutamine, Inotropes, Urea, Adrenergic receptors, 1102 Cardiorespiratory Medicine and Haematology, Excitation Contraction Coupling, Clinical Trials as Topic, Cardiogenic shock, 3. Good health, Receptors, Adrenergic, Mitochondria, Acute Disease, Models, Animal, Cardiology, Nitrogen Oxides, Cardiology and Cardiovascular Medicine, Oxidation-Reduction, medicine.drug, Cardiac function curve, Sarcomeres, medicine.medical_specialty, Cardiotonic Agents, Systole, Shock, Cardiogenic, Heart failure, 03 medical and health sciences, Special Article, Dogs, Internal medicine, Energetics, medicine, Animals, Humans, Simendan, business.industry, 030229 sport sciences, medicine.disease, Myocardial Contraction, Excitation-contraction coupling, Cardiovascular System & Hematology, 3121 General medicine, internal medicine and other clinical medicine, Case-Control Studies, Nitroxyl, Calcium, Human medicine, business, Energy Metabolism
Abstract

Acute heart failure (HF) and in particular, cardiogenic shock are associated with high morbidity and mortality. A therapeutic dilemma is that the use of positive inotropic agents, such as catecholamines or phosphodiesterase-inhibitors, is associated with increased mortality. Newer drugs, such as levosimendan or omecamtiv mecarbil, target sarcomeres to improve systolic function putatively without elevating intracellular Ca2+. Although meta-analyses of smaller trials suggested that levosimendan is associated with a better outcome than dobutamine, larger comparative trials failed to confirm this observation. For omecamtiv mecarbil, Phase II clinical trials suggest a favourable haemodynamic profile in patients with acute and chronic HF, and a Phase III morbidity/mortality trial in patients with chronic HF has recently begun. Here, we review the pathophysiological basis of systolic dysfunction in patients with HF and the mechanisms through which different inotropic agents improve cardiac function. Since adenosine triphosphate and reactive oxygen species production in mitochondria are intimately linked to the processes of excitation–contraction coupling, we also discuss the impact of inotropic agents on mitochondrial bioenergetics and redox regulation. Therefore, this position paper should help identify novel targets for treatments that could not only safely improve systolic and diastolic function acutely, but potentially also myocardial structure and function over a longer-term.

Published
2019

33. Heart failure and diabetes

Author

Christoph, Maack1, Michael, Lehrke2, Johannes, Backs3, Heinzel4, Frank R., Jean-Sebastien, Hulot5, 6, Nikolaus, Marx2, Paulus7, Walter J., Patrick, Rossignol8, Heinrich, Taegtmeyer9, Johann, Bauersachs10, Antoni, Bayes-Genis11, Dirk, Brutsaert13, Heiko, Bugger14, Kieran, Clarke15, Francesco, Cosentino16, Gilles De Keulenaer17, Alessandra Dei Cas18, Arantxa, Gonza´lez20, Martin, Huelsmann21, Iaccarino, Guido, Ida Gjervold Lunde23, Lyon24, Alexander R., Piero, Pollesello25, Graham, Rena26, Riksen27, Niels P., Giuseppe, Rosano28, Bart, Staels30, 31, 32, van Laake34, Lindaw., Christophwanner35, Dimitrios, Farmakis36, Gerasimos, Filippatos36, Frank, Ruschitzka37, Petar, Seferovic38, de Boer39, Rudolf A., and Stephane Heymans, Clinicum, University of Helsinki, University Hospital Wuerzburg / Universitäts­klinikum Würzburg, Universitätsklinikum RWTH Aachen - University Hospital Aachen [Aachen, Germany] (UKA), Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Heidelberg University Hospital [Heidelberg], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], VU University Medical Center [Amsterdam], Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], University of Texas Health Science Center, The University of Texas Health Science Center at Houston (UTHealth), Hannover Medical School [Hannover] (MHH), Germans Trias i Pujol University Hospital [Badalona, Barcelona, Spain] (GTPUH), Universitat Autònoma de Barcelona (UAB), University of Antwerp (UA), Department of Cardiology and Angiology I, University Heart Centre Freiburg - Bad Krozingen, University of Freiburg [Freiburg], University of Oxford, Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], Università degli studi di Parma = University of Parma (UNIPR), Azienda Ospedaliero-Universitaria di Parma, Center for Applied Medical Research [Plamplona] (CIMA), Universidad de Navarra [Pamplona] (UNAV), Institute of Health Carlos III, Navarra Institute for Health Research / Instituto de Investigación Sanitaria de Navarra (IdiSNA), Universidad Pública de Navarra [Espagne] = Public University of Navarra (UPNA)-Universidad de Navarra [Pamplona] (UNAV)-Clínica Universidad de Navarra [Pamplona], Medizinische Universität Wien = Medical University of Vienna, Università degli Studi di Salerno = University of Salerno (UNISA), Oslo University Hospital [Oslo], University of Oslo (UiO), Royal Brompton Hospital, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, University of Dundee, Ninewells Hospital and Medical School [Dundee], Radboud University Medical Center [Nijmegen], St George’s University Hospitals, Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 (EGID), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Utrecht University [Utrecht], National and Kapodistrian University of Athens (NKUA), 'Attikon' University Hospital, University hospital of Zurich [Zurich], University of Belgrade [Belgrade], University Medical Center Groningen [Groningen] (UMCG), Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], The Netherlands Heart Institute, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Maack, C, Lehrke, M, Backs, J, Heinzel, Fr, Hulot, J, Marx, N, Paulus, Wj, Rossignol, P, Taegtmeyer, H, Bauersachs, J, Bayes-Genis, A, Brutsaert, D, Bugger, H, Clarke, K, Cosentino, F, De Keulenaer, G, Dei Cas, A, González, A, Huelsmann, M, Iaccarino, G, Lunde, Ig, Lyon, Ar, Pollesello, P, Rena, G, Riksen, Np, Rosano, G, Staels, B, van Laake, Lw, Wanner, C, Farmakis, D, Filippatos, G, Ruschitzka, F, Seferovic, P, de Boer, Ra, and Heymans, S.

Subjects
medicine.medical_specialty, Cardiac & Cardiovascular Systems, [SDV]Life Sciences [q-bio], education, VENTRICULAR DIASTOLIC FUNCTION, Context (language use), Translational research, 030204 cardiovascular system & hematology, 1102 Cardiovascular Medicine And Haematology, CARDIOVASCULAR OUTCOMES, 03 medical and health sciences, DOUBLE-BLIND, 0302 clinical medicine, Internal medicine, Residual morbidity, Journal Article, Medicine, THIAZOLIDINEDIONE THERAPY, 030212 general & internal medicine, Repurposing, Modern epidemic, IMPROVES CARDIAC-FUNCTION, Science & Technology, COTRANSPORTER 2 INHIBITION, GLUCAGON-LIKE PEPTIDE-1, business.industry, Type 2 Diabetes Mellitus, Heart Failure/Cardiomyopathy, Vascular damage Radboud Institute for Molecular Life Sciences [Radboudumc 16], medicine.disease, KETONE-BODIES, Comorbidity, 3. Good health, Review article, Heart failure (HF), Cardiovascular System & Hematology, PRESERVED EJECTION FRACTION, Current Opinion, Heart failure, 3121 General medicine, internal medicine and other clinical medicine, Cardiology, Cardiovascular System & Cardiology, Human medicine, Cardiology and Cardiovascular Medicine, business, Life Sciences & Biomedicine, MYOCARDIAL TRIGLYCERIDE CONTENT, Kidney disease
Abstract

Altres ajuts: C.M. is supported by the Deutsche Forschungsgemeinschaft (DFG; SFB 894, TRR-219, and Ma 2528/7-1), the German Federal Ministry of Education and Science (BMBF; 01EO1504) and the Corona foundation. J.B. is supported by the DFG (SFB 1118) and the DZHK (German Centre for Cardiovascular Research) and by the BMBF. M.L. is supported by the DFG (SFB TRR 219M-03). R.B. is supported by the Netherlands Heart Foundation (CVON DOSIS 2014-40, CVON SHE-PREDICTS-HF 2017-21, and CVON RED-CVD 2017-11); and the Innovational Research Incentives Scheme program of the Netherlands Organization for Scientific Research (NWO VIDI, grant 917.13.350). N.M. is supported by the DFG (SFB TRR 219M-03, M-05). H.T. is supported by grants from the National Institutes of Health of the US Public Health Service (HL-RO1 061483 and HL-RO1 073162). A.B.G. was supported by grants from the Ministerio de Educación y Ciencia , Fundació La MARATÓ de TV3 (201502, 201516), CIBER Cardiovascular (CB16/11/00403), and AdvanceCat 2014-2020. H.B. is supported by the DFG (Bu2126/3-1). A.D.C. was supported by 'FIL' funds for research from University of Parma. A.G. was supported by grants from the European Union Commission's FP7 programme (HOMAGE and FIBROTARGETS) and ERA-CVD Joint Transnational Call 2016 LYMIT-DIS. G.R. acknowledges recent funding from The Cunningham Trust, MRC (MR/K012924/1) and the Diabetes UK RW and JM Collins studentship. S.H. received funding from the European Union Commission's Seventh Framework programme (2007-2013) under grant agreement N° 305507 (HOMAGE), N° 602904 (FIBROTARGETS) and N° 602156 (HECATOS). S.H. acknowledges the support from the Netherlands Cardiovascular Research Initiative: an initiative with support of the Dutch Heart Foundation, CVON-ARENA-PRIME, CVON-EARLY HFPEF, and SHE-PREDICTS. This research is co-financed as a PPP-allowance Research and Innovation by the Ministry of Economic Affairs within Top Sector Life sciences & Health.

Published
2018

34. The autonomic nervous system as a therapeutic target in heart failure: a scientific position statement from the Translational Research Committee of the Heart Failure Association of the European Society of Cardiology

Author

Marc, van Bilsen, Hitesh C, Patel, Johann, Bauersachs, Michael, Böhm, Martin, Borggrefe, Dirk, Brutsaert, Andrew J S, Coats, Rudolf A, de Boer, Gilles W, de Keulenaer, Gerasimos S, Filippatos, John, Floras, Guido, Grassi, Ewa A, Jankowska, Lilian, Kornet, Ida G, Lunde, Christoph, Maack, Felix, Mahfoud, Piero, Pollesello, Piotr, Ponikowski, Frank, Ruschitzka, Hani N, Sabbah, Harold D, Schultz, Petar, Seferovic, Riemer H J A, Slart, Peter, Taggart, Carlo G, Tocchetti, Linda W, Van Laake, Faiez, Zannad, Stephane, Heymans, Alexander R, Lyon, British Heart Foundation, Fysiologie, RS: CARIM - R2.02 - Cardiomyopathy, Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), University of Zurich, Lyon, Alexander R, van Bilsen, Marc, Patel, Hitesh C., Bauersachs, Johann, Böhm, Michael, Borggrefe, Martin, Brutsaert, Dirk, Coats, Andrew J. S., de Boer, Rudolf A., de Keulenaer, Gilles W., Filippatos, Gerasimos S., Floras, John, Grassi, Guido, Jankowska, Ewa A., Kornet, Lilian, Lunde, Ida G., Maack, Christoph, Mahfoud, Felix, Pollesello, Piero, Ponikowski, Piotr, Ruschitzka, Frank, Sabbah, Hani N., Schultz, Harold D., Seferovic, Petar, Slart, Riemer H. J. A., Taggart, Peter, Tocchetti, Carlo G., Van Laake, Linda W., Zannad, Faiez, Heymans, Stephane, Lyon, Alexander R., Van Bilsen, M, Patel, H, Bauersachs, J, Bã¶hm, M, Borggrefe, M, Brutsaert, D, Coats, A, De Boer, R, De Keulenaer, G, Filippatos, G, Floras, J, Grassi, G, Jankowska, E, Kornet, L, Lunde, I, Maack, C, Mahfoud, F, Pollesello, P, Ponikowski, P, Ruschitzka, F, Sabbah, H, Schultz, H, Seferovic, P, Slart, R, Taggart, P, Tocchetti, C, Van Laake, L, Zannad, F, Heymans, S, and Lyon, A

Subjects
ACUTE MYOCARDIAL-INFARCTION, Consensus, Cardiac & Cardiovascular Systems, RENAL SYMPATHETIC DENERVATION, autonomic dysfunction, Autonomic dysfunction, Cardiology, 610 Medicine & health, Heart failure, Autonomic Nervous System, 1102 Cardiovascular Medicine And Haematology, 2705 Cardiology and Cardiovascular Medicine, Translational Research, Biomedical, LEFT-VENTRICULAR DYSFUNCTION, OBSTRUCTIVE SLEEP-APNEA, Humans, Devices and nerve ablation, RHEOS PIVOTAL TRIAL, Societies, Medical, Science & Technology, Pharmacology. Therapy, Parasympathetic, RANDOMIZED CONTROLLED-TRIAL, BAROREFLEX ACTIVATION THERAPY, Europe, Cardiovascular System & Hematology, 10209 Clinic for Cardiology, Cardiovascular System & Cardiology, CARDIAC RESYNCHRONIZATION THERAPY, Human medicine, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, Sympathetic, REDUCED EJECTION FRACTION, ADAPTIVE SERVO-VENTILATION
Abstract

Despite improvements in medical therapy and device-based treatment, heart failure (HF) continues to impose enormous burdens on patients and health care systems worldwide. Alterations in autonomic nervous system (ANS) activity contribute to cardiac disease progression, and the recent development of invasive techniques and electrical stimulation devices has opened new avenues for specific targeting of the sympathetic and parasympathetic branches of the ANS. The Heart Failure Association of the European Society of Cardiology recently organized an expert workshop which brought together clinicians, trialists and basic scientists to discuss the ANS as a therapeutic target in HF. The questions addressed were: (i) What are the abnormalities of ANS in HF patients? (ii) What methods are available to measure autonomic dysfunction? (iii) What therapeutic interventions are available to target the ANS in patients with HF, and what are their specific strengths and weaknesses? (iv) What have we learned from previous ANS trials? (v) How should we proceed in the future?.

Published
2017

36. Cardiovascular toxicities of immune therapies for cancer - a scientific statement of the Heart Failure Association (HFA) of the ESC and the ESC Council of Cardio-Oncology.

Author

Tocchetti CG, Farmakis D, Koop Y, Andres MS, Couch LS, Formisano L, Ciardiello F, Pane F, Au L, Emmerich M, Plummer C, Gulati G, Ramalingam S, Cardinale D, Brezden-Masley C, Iakobishvili Z, Thavendiranathan P, Santoro C, Bergler-Klein J, Keramida K, de Boer RA, Maack C, Lutgens E, Rassaf T, Fradley MG, Moslehi J, Yang EH, De Keulenaer G, Ameri P, Bax J, Neilan TG, Herrmann J, Mbakwem AC, Mirabel M, Skouri H, Hirsch E, Cohen-Solal A, Sverdlov AL, van der Meer P, Asteggiano R, Barac A, Ky B, Lenihan D, Dent S, Seferovic P, Coats AJS, Metra M, Rosano G, Suter T, Lopez-Fernandez T, and Lyon AR

Abstract

The advent of immunological therapies has revolutionized the treatment of solid and haematological cancers over the last decade. Licensed therapies which activate the immune system to target cancer cells can be broadly divided into two classes. The first class are antibodies that inhibit immune checkpoint signalling, known as immune checkpoint inhibitors (ICIs). The second class are cell-based immune therapies including chimeric antigen receptor T lymphocyte (CAR-T) cell therapies, natural killer (NK) cell therapies, and tumour infiltrating lymphocyte (TIL) therapies. The clinical efficacy of all these treatments generally outweighs the risks, but there is a high rate of immune-related adverse events (irAEs), which are often unpredictable in timing with clinical sequalae ranging from mild (e.g. rash) to severe or even fatal (e.g. myocarditis, cytokine release syndrome) and reversible to permanent (e.g. endocrinopathies).The mechanisms underpinning irAE pathology vary across different irAE complications and syndromes, reflecting the broad clinical phenotypes observed and the variability of different individual immune responses, and are poorly understood overall. Immune-related cardiovascular toxicities have emerged, and our understanding has evolved from focussing initially on rare but fatal ICI-related myocarditis with cardiogenic shock to more common complications including less severe ICI-related myocarditis, pericarditis, arrhythmias, including conduction system disease and heart block, non-inflammatory heart failure, takotsubo syndrome and coronary artery disease. In this scientific statement on the cardiovascular toxicities of immune therapies for cancer, we summarize the pathophysiology, epidemiology, diagnosis, and management of ICI, CAR-T, NK, and TIL therapies. We also highlight gaps in the literature and where future research should focus., (© 2024 European Society of Cardiology.)

Published
2024
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37. Giant native aortic valve thrombus under non-vitamin K antagonist oral anticoagulant: first manifestation of antiphospholipid syndrome.

Author

Vermeersch G, Prihadi E, De Keulenaer G, and Vermeersch P

Subjects
Administration, Oral, Anticoagulants therapeutic use, Aortic Valve diagnostic imaging, Aortic Valve surgery, Humans, Antiphospholipid Syndrome complications, Antiphospholipid Syndrome drug therapy, Thrombosis diagnostic imaging, Thrombosis drug therapy, Thrombosis etiology
Published
2021
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38. A special case of hypertrophic cardiomyopathy with a differential diagnosis of isolated cardiac amyloidosis or junctophilin type 2 associated cardiomyopathy.

Author

De Bruijn S, Galloo X, De Keulenaer G, Prihadi EA, Brands C, and Helbert M

Subjects
Aged, 80 and over, Diagnosis, Differential, Humans, Male, Membrane Proteins, Amyloidosis diagnosis, Cardiomyopathies diagnosis, Cardiomyopathy, Hypertrophic diagnosis
Abstract

Differential diagnosis between hypertrophic cardiomyopathy (HCM) and cardiac amyloidosis (CA) is mandatory since the prognosis is very different, but not always possible as both diseases present with increased myocardial thickness and mass. Despite better knowledge of the pathophysiology of both HCM and CA, and new developments in diagnosis, many patients with cardiac involvement in systemic amyloidosis are still only diagnosed in an advanced stage. Improvements in non-invasive diagnostic methods such as ultrasound techniques and cardiac magnetic resonance imaging will eventually obviate the need for invasive studies in order to prove amyloid cardiomyopathy. Nevertheless, today, an endomyocardial biopsy still remains the golden standard. We present an 86-year-old man, diagnosed with hypertrophic cardiomyopathy, in whom echocardiography and cardiac magnetic resonance imaging strongly suggested amyloidosis to be the underlying cause. Interestingly, a new variant of the junctophilin 2 (JPH2) gene, related to hypertrophic cardiomyopathies, was found in our patient.

Published
2021
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39. Sex differences in circulating proteins in heart failure with preserved ejection fraction.

Author

Stienen S, Ferreira JP, Kobayashi M, Preud'homme G, Dobre D, Machu JL, Duarte K, Bresso E, Devignes MD, Andrés NL, Girerd N, Aakhus S, Ambrosio G, Rocca HB, Fontes-Carvalho R, Fraser AG, van Heerebeek L, de Keulenaer G, Marino P, McDonald K, Mebazaa A, Papp Z, Raddino R, Tschöpe C, Paulus WJ, Zannad F, and Rossignol P

Subjects
Aged, Aged, 80 and over, Biomarkers blood, Female, Humans, Male, Sex Factors, Gene Expression Regulation physiology, Heart Failure metabolism, Stroke Volume physiology
Abstract

Background: Many patients with heart failure with preserved ejection fraction (HFpEF) are women. Exploring mechanisms underlying the sex differences may improve our understanding of the pathophysiology of HFpEF. Studies focusing on sex differences in circulating proteins in HFpEF patients are scarce., Methods: A total of 415 proteins were analyzed in 392 HFpEF patients included in The Metabolic Road to Diastolic Heart Failure: Diastolic Heart Failure study (MEDIA-DHF). Sex differences in these proteins were assessed using adjusted logistic regression analyses. The associations between candidate proteins and cardiovascular (CV) death or CV hospitalization (with sex interaction) were assessed using Cox regression models., Results: We found 9 proteins to be differentially expressed between female and male patients. Women expressed more LPL and PLIN1, which are markers of lipid metabolism; more LHB, IGFBP3, and IL1RL2 as markers of transcriptional regulation; and more Ep-CAM as marker of hemostasis. Women expressed less MMP-3, which is a marker associated with extracellular matrix organization; less NRP1, which is associated with developmental processes; and less ACE2, which is related to metabolism. Sex was not associated with the study outcomes (adj. HR 1.48, 95% CI 0.83-2.63), p = 0.18., Conclusion: In chronic HFpEF, assessing sex differences in a wide range of circulating proteins led to the identification of 9 proteins that were differentially expressed between female and male patients. These findings may help further investigations into potential pathophysiological processes contributing to HFpEF.

Published
2020
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40. Enhanced clinical phenotyping by mechanistic bioprofiling in heart failure with preserved ejection fraction: insights from the MEDIA-DHF study (The Metabolic Road to Diastolic Heart Failure).

Author

Stienen S, Ferreira JP, Kobayashi M, Preud'homme G, Dobre D, Machu JL, Duarte K, Bresso E, Devignes MD, López N, Girerd N, Aakhus S, Ambrosio G, Brunner-La Rocca HP, Fontes-Carvalho R, Fraser AG, van Heerebeek L, Heymans S, de Keulenaer G, Marino P, McDonald K, Mebazaa A, Papp Z, Raddino R, Tschöpe C, Paulus WJ, Zannad F, and Rossignol P

Subjects
Aged, Biomarkers analysis, Cluster Analysis, Female, Humans, Machine Learning, Male, Middle Aged, Proteomics, Stroke Volume, Heart Failure physiopathology, Phenotype
Abstract

Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome for which clear evidence of effective therapies is lacking. Understanding which factors determine this heterogeneity may be helped by better phenotyping. An unsupervised statistical approach applied to a large set of biomarkers may identify distinct HFpEF phenotypes. Methods: Relevant proteomic biomarkers were analyzed in 392 HFpEF patients included in Metabolic Road to Diastolic HF (MEDIA-DHF). We performed an unsupervised cluster analysis to define distinct phenotypes. Cluster characteristics were explored with logistic regression. The association between clusters and 1-year cardiovascular (CV) death and/or CV hospitalization was studied using Cox regression. Results: Based on 415 biomarkers, we identified 2 distinct clusters. Clinical variables associated with cluster 2 were diabetes, impaired renal function, loop diuretics and/or betablockers. In addition, 17 biomarkers were higher expressed in cluster 2 vs. 1. Patients in cluster 2 vs. those in 1 experienced higher rates of CV death/CV hospitalization (adj. HR 1.93, 95% CI 1.12-3.32, p  = 0.017). Complex-network analyses linked these biomarkers to immune system activation, signal transduction cascades, cell interactions and metabolism. Conclusion: Unsupervised machine-learning algorithms applied to a wide range of biomarkers identified 2 HFpEF clusters with different CV phenotypes and outcomes. The identified pathways may provide a basis for future research.Clinical significanceMore insight is obtained in the mechanisms related to poor outcome in HFpEF patients since it was demonstrated that biomarkers associated with the high-risk cluster were related to the immune system, signal transduction cascades, cell interactions and metabolismBiomarkers (and pathways) identified in this study may help select high-risk HFpEF patients which could be helpful for the inclusion/exclusion of patients in future trials.Our findings may be the basis of investigating therapies specifically targeting these pathways and the potential use of corresponding markers potentially identifying patients with distinct mechanistic bioprofiles most likely to respond to the selected mechanistically targeted therapies.

Published
2020
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41. Treatments targeting inotropy.

Author

Maack C, Eschenhagen T, Hamdani N, Heinzel FR, Lyon AR, Manstein DJ, Metzger J, Papp Z, Tocchetti CG, Yilmaz MB, Anker SD, Balligand JL, Bauersachs J, Brutsaert D, Carrier L, Chlopicki S, Cleland JG, de Boer RA, Dietl A, Fischmeister R, Harjola VP, Heymans S, Hilfiker-Kleiner D, Holzmeister J, de Keulenaer G, Limongelli G, Linke WA, Lund LH, Masip J, Metra M, Mueller C, Pieske B, Ponikowski P, Ristić A, Ruschitzka F, Seferović PM, Skouri H, Zimmermann WH, and Mebazaa A

Subjects
Acute Disease, Animals, Antioxidants adverse effects, Antioxidants therapeutic use, Calcium metabolism, Cardiotonic Agents adverse effects, Case-Control Studies, Catecholamines adverse effects, Catecholamines therapeutic use, Clinical Trials as Topic, Diastole drug effects, Dobutamine adverse effects, Dobutamine therapeutic use, Dogs, Energy Metabolism drug effects, Heart Failure mortality, Humans, Mitochondria metabolism, Models, Animal, Myocardial Contraction drug effects, Nitrogen Oxides adverse effects, Nitrogen Oxides therapeutic use, Oxidation-Reduction drug effects, Phosphodiesterase Inhibitors adverse effects, Phosphodiesterase Inhibitors therapeutic use, Placebos administration & dosage, Receptors, Adrenergic drug effects, Sarcomeres drug effects, Sarcomeres metabolism, Shock, Cardiogenic mortality, Simendan adverse effects, Simendan therapeutic use, Swine, Systole drug effects, Urea adverse effects, Urea analogs & derivatives, Urea therapeutic use, Cardiotonic Agents therapeutic use, Excitation Contraction Coupling drug effects, Heart Failure drug therapy, Shock, Cardiogenic drug therapy
Abstract

Acute heart failure (HF) and in particular, cardiogenic shock are associated with high morbidity and mortality. A therapeutic dilemma is that the use of positive inotropic agents, such as catecholamines or phosphodiesterase-inhibitors, is associated with increased mortality. Newer drugs, such as levosimendan or omecamtiv mecarbil, target sarcomeres to improve systolic function putatively without elevating intracellular Ca2+. Although meta-analyses of smaller trials suggested that levosimendan is associated with a better outcome than dobutamine, larger comparative trials failed to confirm this observation. For omecamtiv mecarbil, Phase II clinical trials suggest a favourable haemodynamic profile in patients with acute and chronic HF, and a Phase III morbidity/mortality trial in patients with chronic HF has recently begun. Here, we review the pathophysiological basis of systolic dysfunction in patients with HF and the mechanisms through which different inotropic agents improve cardiac function. Since adenosine triphosphate and reactive oxygen species production in mitochondria are intimately linked to the processes of excitation-contraction coupling, we also discuss the impact of inotropic agents on mitochondrial bioenergetics and redox regulation. Therefore, this position paper should help identify novel targets for treatments that could not only safely improve systolic and diastolic function acutely, but potentially also myocardial structure and function over a longer-term., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Published
2019
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42. Long-term impact of a six-month telemedical care programme on mortality, heart failure readmissions and healthcare costs in patients with chronic heart failure.

Author

Frederix I, Vanderlinden L, Verboven AS, Welten M, Wouters D, De Keulenaer G, Ector B, Elegeert I, Troisfontaines P, Weytjens C, Mullens W, and Dendale P

Subjects
Aged, Aged, 80 and over, Chronic Disease, Female, Follow-Up Studies, Heart Failure mortality, Humans, Male, Middle Aged, Patient Readmission statistics & numerical data, Prospective Studies, Telemedicine economics, Health Expenditures statistics & numerical data, Heart Failure therapy, Telemedicine organization & administration, Telemedicine statistics & numerical data
Abstract

Aims: The TElemonitoring in the MAnagement of Heart Failure (TEMA-HF) 1 long-term follow-up study assessed whether an initial six-month telemonitoring (TM) programme compared with usual care (UC) would result in reduced all-cause mortality, heart failure admissions and healthcare costs in chronic heart failure (CHF) patients at long-term follow-up., Methods: Of the 160 patients included in the multi-centre, randomised controlled telemonitoring trial (TEMA-HF 1, time point t 0 ); 142 CHF patients (65% male; age: 76 ± 10 years; EF: 36 ± 15%) were alive and entered the follow-up study (time point: t 1 ) with a final evaluation at 79 months (time point: t 2 ). Both TM and UC group patients received standard heart failure care during the follow-up study (time points: t 1 - t 2 ). The primary endpoint was all-cause mortality. Secondary outcomes included days lost due to heart failure readmissions and readmission/patient follow-up related healthcare costs., Results: Compared with usual care, the initial six-month TM programme had no significant effect on all-cause mortality (hazard ratio: 0.83; 95% confidence interval, 0.57 to 1.20; p = 0.32). The number of days lost due to heart failure readmissions was significantly lower in the TM group ( p = 0.04). Healthcare costs did not differ significantly between the TM (€ 9140 ± 10580) and UC group (€ 12495 ± 22433) ( p = 0.87)., Discussion: An initial six-month telemonitoring programme was not associated with reduced all-cause mortality in CHF patients at long-term follow-up but resulted in a reduction in the number of days lost due to heart failure readmissions. This study is registered in the ClinicalTrials.gov registry (NCT03171038) (URL: https://clinicaltrials.gov/ct2/show/NCT03171038 ).

Published
2019
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43. Towards better definition, quantification and treatment of fibrosis in heart failure. A scientific roadmap by the Committee of Translational Research of the Heart Failure Association (HFA) of the European Society of Cardiology.

Author

de Boer RA, De Keulenaer G, Bauersachs J, Brutsaert D, Cleland JG, Diez J, Du XJ, Ford P, Heinzel FR, Lipson KE, McDonagh T, Lopez-Andres N, Lunde IG, Lyon AR, Pollesello P, Prasad SK, Tocchetti CG, Mayr M, Sluijter JPG, Thum T, Tschöpe C, Zannad F, Zimmermann WH, Ruschitzka F, Filippatos G, Lindsey ML, Maack C, and Heymans S

Subjects
Biomarkers blood, Cardiac Imaging Techniques methods, Disease Management, Europe, Humans, Prognosis, Research, Societies, Medical, Translational Research, Biomedical, Extracellular Matrix Proteins blood, Fibrosis classification, Fibrosis diagnosis, Fibrosis physiopathology, Fibrosis therapy, Heart Failure diagnosis, Heart Failure physiopathology, Heart Failure therapy, Myocardium metabolism, Myocardium pathology
Abstract

Fibrosis is a pivotal player in heart failure development and progression. Measurements of (markers of) fibrosis in tissue and blood may help to diagnose and risk stratify patients with heart failure, and its treatment may be effective in preventing heart failure and its progression. A lack of pathophysiological insights and uniform definitions has hampered the research in fibrosis and heart failure. The Translational Research Committee of the Heart Failure Association discussed several aspects of fibrosis in their workshop. Early insidious perturbations such as subclinical hypertension or inflammation may trigger first fibrotic events, while more dramatic triggers such as myocardial infarction and myocarditis give rise to full blown scar formation and ongoing fibrosis in diseased hearts. Aging itself is also associated with a cardiac phenotype that includes fibrosis. Fibrosis is an extremely heterogeneous phenomenon, as several stages of the fibrotic process exist, each with different fibrosis subtypes and a different composition of various cells and proteins - resulting in a very complex pathophysiology. As a result, detection of fibrosis, e.g. using current cardiac imaging modalities or plasma biomarkers, will detect only specific subforms of fibrosis, but cannot capture all aspects of the complex fibrotic process. Furthermore, several anti-fibrotic therapies are under investigation, but such therapies generally target aspecific aspects of the fibrotic process and suffer from a lack of precision. This review discusses the mechanisms and the caveats and proposes a roadmap for future research., (© 2019 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Published
2019
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44. Heart failure and diabetes: metabolic alterations and therapeutic interventions: a state-of-the-art review from the Translational Research Committee of the Heart Failure Association-European Society of Cardiology.

Author

Maack C, Lehrke M, Backs J, Heinzel FR, Hulot JS, Marx N, Paulus WJ, Rossignol P, Taegtmeyer H, Bauersachs J, Bayes-Genis A, Brutsaert D, Bugger H, Clarke K, Cosentino F, De Keulenaer G, Dei Cas A, González A, Huelsmann M, Iaccarino G, Lunde IG, Lyon AR, Pollesello P, Rena G, Riksen NP, Rosano G, Staels B, van Laake LW, Wanner C, Farmakis D, Filippatos G, Ruschitzka F, Seferovic P, de Boer RA, and Heymans S

Subjects
Aged, Aged, 80 and over, Comorbidity, Diabetes Mellitus epidemiology, Diabetes Mellitus therapy, Europe, Female, Heart Failure epidemiology, Heart Failure mortality, Heart Failure physiopathology, Humans, Hypoglycemic Agents adverse effects, Hypoglycemic Agents therapeutic use, Insulin Resistance, Male, Obesity complications, Obesity epidemiology, Renal Insufficiency, Chronic complications, Renal Insufficiency, Chronic epidemiology, Socioeconomic Factors, Sulfonylurea Compounds adverse effects, Sulfonylurea Compounds therapeutic use, Diabetes Mellitus drug therapy, Heart Failure therapy, Societies, Medical organization & administration, Translational Research, Biomedical methods
Published
2018
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45. Phenotypical characterization of α-galactosidase A gene mutations identified in a large Fabry disease screening program in stroke in the young.

Author

De Brabander I, Yperzeele L, Ceuterick-De Groote C, Brouns R, Baker R, Belachew S, Delbecq J, De Keulenaer G, Dethy S, Eyskens F, Fumal A, Hemelsoet D, Hughes D, Jeangette S, Nuytten D, Redondo P, Sadzot B, Sindic C, Sheorajpanday R, Thijs V, Van Broeckhoven C, and De Deyn PP

Subjects
Adult, Belgium epidemiology, Echocardiography, Electrocardiography, Fabry Disease epidemiology, Female, Genetic Testing, Glycolipids blood, Glycolipids urine, Humans, Male, Mutation physiology, Phenotype, Skin pathology, Sphingolipids blood, Sphingolipids urine, Stroke epidemiology, Trihexosylceramides blood, Trihexosylceramides urine, Vertebrobasilar Insufficiency pathology, Young Adult, alpha-Galactosidase blood, alpha-Galactosidase urine, Fabry Disease genetics, Mutation genetics, Stroke genetics, alpha-Galactosidase genetics
Abstract

Objective: In the Belgian Fabry Study (BeFaS), the prevalence of Fabry disease was assessed in 1000 young patients presenting with stroke, unexplained white matter lesions or vertebrobasilar dolichoectasia. The results of the BeFaS suggested that Fabry disease may play a role in up to 1% of young patients presenting with cerebrovascular disease. However, the clinical relevance was unclear in all cases. We report on detailed phenotyping in subjects identified with α-galactosidase A (α-Gal A) enzyme deficiency or GLA mutations identified in the BeFaS (n=10), and on the results of family screening in this population., Methods: Family screening was performed to identify additional mutation carriers. Biochemical and/or clinical evaluation of all subjects (BeFaS index patients and relatives carrying a GLA mutation) was performed., Results: Genetic family screening revealed 18 additional GLA mutation carriers. Bloodspot α-Gal A enzyme activity was normal in all GLA mutation carriers, even in 2 males with the p.A143T mutation. Plasma Gb3 and lyso-Gb3 levels were normal in all subjects. Elevated Gb3 in urine was detected in 2 subjects. Some classic clinical signs of Fabry disease, like angiokeratoma or cornea verticillata, could not be detected in our population. Cardiac symptoms of Fabry disease were found in 6 out of 10 p.A143T carriers. No signs of cerebrovascular disease were found in the relatives with a GLA mutation., Conclusions: We could not identify mutations causing the classical clinical phenotype of Fabry disease in our cerebrovascular disease population. Enzyme activity analysis in bloodspots and plasma may fail to identify late-onset variants of Fabry disease. We recommend genetic testing when an atypical, late-onset variant of Fabry disease is suspected in a male cerebrovascular disease patient. However, this may lead to the identification of non-disease causing or controversial genetic variants., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Published
2013
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46. Cardiotoxicity associated with cancer therapy: pathophysiology and prevention strategies.

Author

Adão R, de Keulenaer G, Leite-Moreira A, and Brás-Silva C

Subjects
Anthracyclines adverse effects, Antibodies, Monoclonal, Humanized adverse effects, Heart Diseases etiology, Humans, Trastuzumab, Antineoplastic Agents adverse effects, Heart Diseases physiopathology, Heart Diseases prevention & control, Neoplasms drug therapy, Neoplasms radiotherapy, Radiation Injuries complications
Abstract

Cardiotoxicity is one of the most significant adverse effects of cancer treatment, and is responsible for considerable morbidity and mortality. Among the effects of chemotherapeutic agents on the cardiovascular system, the most frequent and serious is heart failure with ventricular systolic dysfunction. Other toxic effects include hypertension, thromboembolic disease, pericardial disease, arrhythmias and myocardial ischemia. For several decades, cancer therapy-induced cardiomyopathy was almost exclusively associated with the use of cumulative doses of anthracyclines, which cause permanent damage at the cellular level. However, new therapeutic agents, such as the monoclonal antibody trastuzumab, induce transient reversible myocyte dysfunction which is unrelated to the dose used. Early identification of potential cardiovascular injury, accurate diagnosis of cardiotoxic events and implementation of appropriate monitoring plans are essential in patients with cancer. Close cooperation between cardiologists and oncologists is thus crucial, in order to balance the risks and benefits of cardiotoxic anticancer therapy. In this article we review the various responses to cardiotoxic cancer treatments and their relationship with the main antineoplastic drugs used in clinical practice. In addition, we discuss the main guidelines on detection and monitoring of cardiotoxicity in patients with cancer., (Copyright © 2012 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.)

Published
2013
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47. Impact of radiofrequency characteristics on acute pulmonary vein reconnection and clinical outcome after PVAC ablation.

Author

De Greef Y, Tavernier R, Schwagten B, De Keulenaer G, Stockman D, and Duytschaever M

Subjects
Adenosine, Aged, Atrial Fibrillation diagnosis, Atrial Fibrillation physiopathology, Disease-Free Survival, Electrophysiologic Techniques, Cardiac, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Predictive Value of Tests, Pulmonary Veins physiopathology, Recurrence, Signal Processing, Computer-Assisted, Software, Time Factors, Treatment Outcome, Atrial Fibrillation surgery, Catheter Ablation adverse effects, Pulmonary Veins surgery
Abstract

Objective: The objective was to study the impact of radiofrequency (RF) characteristics on acute pulmonary vein reconnection (PVR) and outcome after PVAC ablation. PVI with additional ablation of PVR (PVI + PVR) was compared to PVI-only., Methods: In 40 consecutive patients, after PVAC-guided PVI, adenosine and a 1-hour waiting time were used to unmask and ablate acute PVR (PVI + PVR group). RF-characteristics and 1-year AF freedom were compared post hoc to 40 clinically matched patients undergoing PVI only (PVI-only group). Custom-made software was used to assess RF characteristics of the PVAC applications needed to obtain baseline PVI., Results: There was no difference in clinical characteristics or baseline RF-profile between both groups. Acute PVR was observed and ablated in 38 of 160 veins (24%). AF-freedom after PVI + PVR was higher than PVI (85% vs 65%, P < 0.05). Within the PVI group, comparing patients with and without AF-recurrence, the percentage of PVAC applications with high T° (>48°) but low power (<3W) was higher (28 ± 18% vs 11 ± 11%, P < 0.0001). Within the PVI + PVR group, when comparing PVs with and without PVR, the percentage of low power/high T° PVAC applications was also higher (27 ± 13% vs 13 ± 15%, P < 0.0001)., Conclusions: (1) After PVAC ablation, 24% of PVs exhibit acute reconnection. Additional ablation of reconnection improves clinical outcome. (2) Acute reconnection as well as clinical recurrence of AF are characterized by PVAC ablation with a considerable number of applications with high temperature but low power. (3) If PV isolation is obtained with low power applications, a consistent use of both adenosine and waiting time is required., (© 2012 Wiley Periodicals, Inc.)

Published
2013
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48. [Neuregulin1/ErbB system: importance in the control of cardiovascular function].

Author

Lopes-Conceição L, Dias-Neto M, Fontes-Sousa AP, Mendes-Ferreira P, Maia-Rocha C, Henriques-Coelho T, de Keulenaer G, Leite Moreira AF, and Brás-Silva C

Subjects
Humans, Heart physiology, Neuregulin-1 physiology, Oncogene Proteins v-erbB physiology
Abstract

The family of Neuregulins (NRG), growth factors like epidermal growth factor, is known to induce growth and differentiation of epithelial, glial, neuronal, and skeletal muscle cells. This family comprises four members, being NRG1 the most largely studied, particularly at the cardiovascular level. The biological effects of NRG1 in the adult heart are mediated by the tyrosine kinase receptors ErbB. In the adult heart, NRG1 is expressed by cells of the endocardial endothelium and the cardiac microvascular endothelium, and the receptors ErbB2/ErbB4 are expressed by ventricular cardiomyocytes and are located in T-tubule system and intercalated disks in close proximity to the system components of excitation-contraction coupling. The importance of the NRG/ErbB signaling axis at the cardiovascular level became evident after discovering that patients treated with trastuzumab (inhibitory antibody against ErbB2, used in the treatment of breast cancer) can develop ventricular dysfunction and have higher risk of cardiomyopathy when co-administered with anthracyclines. Subsequent studies in vitro and in vivo have clarified the effects and the respective signaling pathways associated with the NRG/ErbB system in the adult heart. Some cardiovascular functions of the NRG1/ErbB system have been described at the vascular (stimulation of angiogenesis and ateroprotector effect) and myocardium level (negative inotropic effect) as well as effect on the survival, cell growth and organization of the cardiomyocytes (myofibrillar organization and cell-to-cell contact between cardiomyocytes). Furthermore, the interaction of this system with other neurohumoral mediators has been studied. Thus, there seems to be a physiological role in modulating the sympathovagal balance and an interaction with endothelin-1 signaling. All these effects result from the activation of different intracellular signaling cascades, as a consequence of the binding of NRG1 to ErbB receptors. Some cardiac signaling pathways identified until now include molecules such as MEK / Erk 1/2, phosphatidylinositol 3-kinase/ Akt, focal adhesion kinase, Gab (Grb-2-associated binder) family, vascular endothelial growth factor and NO production by endothelial nitric oxide synthase. Thus, the aim of this paper was to make an up-to-date review of existing information on NRG1/ErbB signaling axis, with particular focus on its cardiovascular effects.

Published
2011

49. Expression and spatial heterogeneity of dipeptidyl peptidases in endothelial cells of conduct vessels and capillaries.

Author

Matheeussen V, Baerts L, De Meyer G, De Keulenaer G, Van der Veken P, Augustyns K, Dubois V, Scharpé S, and De Meester I

Subjects
Animals, Aorta cytology, Aorta enzymology, Capillaries cytology, Carotid Arteries cytology, Carotid Arteries enzymology, Cell Line, Dipeptidyl-Peptidase IV Inhibitors pharmacology, Endothelial Cells drug effects, Endothelium, Vascular cytology, Humans, Myocardium enzymology, Pyrazines pharmacology, Rats, Sitagliptin Phosphate, Triazoles pharmacology, Dipeptidyl Peptidase 4 metabolism, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases metabolism, Endothelial Cells enzymology, Endothelium, Vascular enzymology
Abstract

Dipeptidyl peptidase IV (DPPIV)/CD26 is by far the most extensively studied member of the prolyl oligopeptidase family of serine proteases. The discovery of the related enzymes DPP8 and DPP9 necessitates a (re-)evaluation of the DPPIV-like enzymatic activity in cells and organs. In this study, we aimed (1) to investigate the expression of the individual dipeptidyl peptidases in different types of endothelial cells (ECs) and (2) to reconsider published data in relation to our findings. Examination of DPP expression in rat primary ECs of aortic, endocardial and cardiac microvascular origin revealed the presence of DPPIV-like activity in all cell lysates. More than half of this activity could be attributed to DPP8/9. Western blot analysis revealed an abundance of the DPP8 protein as compared to DPP9. The expression of DPPIV and DPP8 was significantly higher in the cardiac microvascular endothelium than in the other ECs, suggesting a more pronounced role of these DPPs in the microvasculature. In situ, DPP activity in ventricular microvasculature was completely inhibited by sitagliptin, indicating that DPPIV is the predominant DPPIV-like enzyme in this organ. By contrast, immunohistochemical studies indicated DPP9 as the predominant DPP in human carotid artery ECs. In conclusion, our results support a highly regulated expression of individual DPPs in ECs, with a spatial heterogeneity in the cardiovascular tree.

Published
2011
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50. Evidence that intracoronary-injected CD133+ peripheral blood progenitor cells home to the myocardium in chronic postinfarction heart failure.

Author

Schots R, De Keulenaer G, Schoors D, Caveliers V, Dujardin M, Verheye S, Van Camp G, Franken PR, Roland J, Van Riet I, and Everaert H

Subjects
AC133 Antigen, Aged, Chronic Disease, Female, Humans, Male, Middle Aged, Myocardial Infarction immunology, Stem Cells immunology, Antigens, CD immunology, Glycoproteins immunology, Heart Failure pathology, Myocardial Infarction pathology, Myocardium pathology, Peptides immunology, Stem Cells cytology
Abstract

Objective: To study the biodistribution of purified CD133(+) cells after intracoronary injection in patients with stable chronic postinfarction heart failure., Patients and Methods: Patients with longstanding myocardial infarction (>12 months prior to inclusion) and with an accessible left coronary artery were eligible. CD133(+) cells were mobilized with granulocyte colony-stimulating factor and purified with a CliniMACS device. Cells were labeled with (111)Indium and injected through a balloon catheter in a coronary artery feeding the necrotic or viable infarct-related region of the left ventricle during a standard coronary catheterization procedure. The total body biodistribution of (111)Indium was studied with a dual-head gamma camera in combination with (99m)Technetium-sestaMIBI cardiac distribution analysis., Results: The number of CD133(+) cells injected ranged between 5 and 10 x 10(6) cells (low dose, three patients) or between 18.5 and 50 x 10(6) cells (high dose, five patients). In the five patients receiving the higher cell doses, a clear residual radioactivity was observed at the level of the chronic injury at 2, 12, and up to 36 hours after injection. A detailed analysis in two patients showed 6.9% to 8.0% (after 2 hours) and 2.3% to 3.2% (after 12 hours) residual radioactivity at the heart. No adverse events were observed during the procedure and up to 3 months follow-up., Conclusions: We demonstrate that CD133(+) progenitor cells are capable of homing to the postinfarction remodeling myocardium after intracoronary injections in patients with chronic postinfarction heart failure.

Published
2007
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