4 research outputs found
Cochlear hair cell fate determination and differentiation in vitro
- Publication venue
- UCL (University College London)
- Publication date
- 01/01/1999
- Field of study
Mammalian cochlear hair cells are relatively inaccessible and few in number. This hampers any research on their fate determination and differentiation. The production of conditionally immortal cell lines from the H2KbtsA58 transgenic mouse should overcome these difficulties. The aims of the present study were threefold. Firstly, to establish that the cell lines provide a viable in vitro system, by examining the pattern of molecular expression in the cochlear hair cell line UB/OC-1. Secondly, to examine differentiation by using clonal derivatives from the heterogeneous cell line UB/OC-l. Thirdly, to explore the process of lateral specification in the determination of cell fate and to explain the differentiation of hair cells and supporting cells from a common precursor. The methods used were cell culture, immunocytochemistry, reverse transcription polymerase chain reaction and western blot. The results demonstrated that firstly; the temporal expression pattern of Brn3.1, an essential transcription factor required for hair cell differentiation, and the a9 subunit of the nicotinic acetylcholine receptor, followed a similar pattern to that during normal development. Secondly, epithelial cell markers such as, vimentin, cytokeratin, actin and cadherin, and specific hair cell markers such as myosinVIIA and fimbrin were expressed when the hair cells differentiated. The pattern of expression suggested parallel pathways of gene expression during differentiation of hair cells. Thirdly, from the expression of Numblike, Notch 1, Jagged I and Jagged2, factors which are known to be involved in lateral specification, a model is proposed to explain hair cell fate determination. The results also demonstrate the much greater experimental flexibility offered by cell lines in understanding hair cell development. Future studies will focus on functional experiments that alter hair cell fate
Finishing the euchromatic sequence of the human genome
- Author
- . Haifeng
- . Magner
- . Yin
- Abbott Scott
- Abbott-Ozersky Amanda
- Abdellah Zahra
- Abouelleil Amr
- Abrajano Anne
- Adachi Tamami
- Adam Catherine
- Adams Charles Q.
- Adamson Aaron
- Adekoya Emmanuel
- Adio-Oduola Babajide
- Aerts Andrea
- Aggarwal Arun
- Ahmadi Alireza
- Ahmed Shahana
- Aimable Matthew
- Ainscough Rachael
- Ait-Zahra Mostafa
- Aizu Tomoyuki
- Alcivare Dana
- Alegria Michelle
- Ali Alla
- Ali Johar
- Allegria-hartmann Michelle
- Alleman Jennifer
- Allen Carlana C.
- Allen Heather
- Allen Nicole R.
- Allen Susan
- Allen Thaddeus
- Almeida Jeff
- Almond Claire
- Alsbrooks Stephen L.
- Altherr Michael R.
- Amaratunge Harshinie C.
- Ambler Andrew
- Ambrose Karen
- Ambrose Kerrie
- Amemiya Chris
- Amico-Keller Gina
- Amin Amita G.
- Anderson Mechele
- Anderson Scott
- Anderson Scott
- Andora Janice
- Andredesz Carol
- Andrew Robert
- Andrews Dan
- Andrews Daniel
- Andrews Neil
- Andrews Stephanie
- Andriese Tim
- Anthouard VĂ©ronique
- Antonarakis Stylianos E.
- Anyalebechi Vivian
- Aoki Norie
- Apostolou Sinoula
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- Keys David
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- Khan Ziad Mohid
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- Kosiura Anna
- Kou Zhaohui
- Kovar Christie L.
- Krawczyk Marie-Claude
- Kremitzki Colin
- Kremmidiotis Gabriel
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- Kruchowski Scott S.
- Kube Michael
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- Lowenstein Michael G.
- Lowry Stephen
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- Lucier Raymond L.
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- MacLean Christine
- Madabhushi Ramki
- Madu Renita C.
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- Manohar Chitra
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- Marquis-Homeyer Catherine
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- Marra Marco
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- McNinch Jenny
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- Nwokenkwo Stanley
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- Okwuonu Geoffrey O.
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- Olarnpunsagoon Alisa
- Olivas Jason
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- Olson Maynard V.
- Omotosho Bamidele
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- Ow David
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- Paul Heidie A.
- Paul Shelia
- Paulson Edward
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- Pennacchio Len A.
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- Percy Chantel
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- Perez Lesette M.
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- Rise Cecil
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- Sasaki Takashi
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- Schatzkamer Kyriena L.
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- Sonnhammer Erik
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- Subramanian Sandhya
- Sudbrak Ralf
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- Sulston John
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- Sun Min
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- Sun Yongqiao
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- Sutherland Grant R.
- Sutherland Robert D.
- Sutton Angelica E.
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- Tan Xinyu
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- Taudien Stefan
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- Tong Jingli
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- Wu Chungen
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- Zhang Haiqing
- Zhang Haiqing
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- Zhang Hongbo
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- Zhang Jingjing
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- Zhang Jiuchun
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- Zhang Li
- Zhang Meihua
- Zhang Meng
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- Zhang Ruhua
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- Zhang Xianglin
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- Zhang Xiuqing
- Zhang Yan
- Zhang Yi
- Zhang Yilin
- Zhang Yilin
- Zhang Ying
- Zhang Yuansen
- Zhang Yuzhi
- Zhang Zhengdong
- Zhao Hongmei
- Zhao Lijian
- Zhao Shenru
- Zhao Zhijing
- Zhen Zhicheng
- Zheng Haibo
- Zhong Ming
- Zhou Carol
- Zhou Haixia
- Zhou Jianling
- Zhou Nannan
- Zhou Xinfeng
- Zhou Yan
- Zhou Yang
- Zhou Yi
- Zhu Bingying
- Zhu Bofeng
- Zhu Fenghua
- Zhu Genfeng
- Zhu Genfeng
- Zhu Miao
- Zhu Ning
- Zhu Yongge
- Zhu Zhen
- Zhuang Shitao
- Zierten Deborah
- Zimmer Andrew
- Zody Michael C.
- Zollo Massimo
- Zorrilla Sara E.
- Zuo Lin
- Publication venue
- LSU Digital Commons
- Publication date
- 21/10/2004
- Field of study
The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers âŒ99% of the euchromatic genome and is accurate to an error rate of âŒ1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead
Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTICâHF: baseline characteristics and comparison with contemporary clinical trials
- Author
- Aaronson Keith
- Abadier Rafik
- Abbasi Siddique A.
- Abdullah Shuaib
- Abelson Mark
- Abhayaratna Walter
- Ablasser Klemens
- Aboyans Victor
- AboâAuda Wael
- Abuannadi Mohammad
- Adams Kirkwood
- Adams Kirkwood F.
- Adhya Shaumik
- Adler Alexander
- Aggarwala Gaurav
- Agostoni Piergiuseppe
- Ahmad Saad
- Aiub Jorge Roberto
- Al Mohammad Abdallah
- Alharethi Rami
- Alieksieieva Liudmyla
- Almeida Filipa
- Almousalli Omar
- Amano Tetsuya
- Amanullah Aman
- Ambardekar Amrut
- Amerena John
- Anand Inder
- Anderson William
- Ando Kenji
- Andreka Peter
- Antalik Lubomir
- Aradi Daniel
- Araiza Raul Reyes
- Arbolishvili Georgy
- Ariani Mehrdad
- AriasâMendoza Alexandra
- Arora Raveen
- Arroyo Julian Alonso Coronel
- Artis Andre
- Asakura Masanori
- Asano Hiroshi
- Ashcom Thomas
- Aslam Shamaila
- Asubiaro Joshua
- Atherton John
- Avaca Horacio Alberto
- Babapulle Mohan
- Bacal Fernando
- Badak Ozer
- Badariene Jolita
- Badat Aysha
- Baker Mathue
- Balsam Pawel
- Banerji Sourin
- Barbarash Olga
- Barbetseas Ioannis
- Barr Craig
- Barros e Silva Pedro Gabriel Melo
- Barua Rajat
- Bauerlein Eugene Joseph
- Baweja Paramdeep
- Bednarkiewicz Zbigniew
- Beelen Driek
- Begg Alistair
- Bekar Lutfu
- Belenkiy Dmitriy
- Belohlavek Jan
- Beltrame John
- Berdague Philippe
- Berglund Stefan
- Berk Martin
- Berkowski Piotr
- Berra Fernando Colombo
- Bertolet Barry
- Besada Diego Alejandro
- Beug Daniel
- Bezzegh Katalin
- Bhagwat Ravi
- Bhargava Rakesh
- BieringâSĂžrensen Tor
- Bilato Claudio
- Blicharski Tomasz
- Boccalandro Fernando
- Boehm Michael
- Boehmer John
- Bogaev Roberta
- Bolshakova Olga
- Boman Kurt
- Bonderman Diana
- Bonet Luis Almenar
- Bonfanti Alberto Cadena
- Bordonava Anselmo Paulino
- Bostick Brian
- Boswijk Dirk
- Bourgeois Ronald
- Bourhaial Hakima
- Bouza Manuel
- Braga Joao Carlos
- Brasca Daniela Garcia
- Brinkley Douglas
- Brito Dulce
- Brunetti Natale Daniele
- Bruno Marco Raul Litvak
- Bu Peili
- Burgess Lesley
- Busak Ladislav
- Buynak Robert
- Buysschaert Ian
- Bykov Alexander
- Böhm Michael
- Caccavo Alberto
- Canesin Manoel
- Cardona Jose
- Cardoso Juliano
- Carluccio Erberto
- Carrasco Jose Alfredo Pagola
- Carson Peter
- Castillo Armando Garcia
- Cavallini Claudio
- Cavusoglu Yuksel
- Cech Vladimir
- Celik Ahmet
- Celutkiene Jelena
- Cepelak Michal
- Cerci Rodrigo Julio
- Chandra Lokesh
- Chandrasekaran Badrinathan
- Chang David
- Chaves Renato
- Chehayeb Raja
- Cheirif Jorge
- Chen Guoqin
- Chen Jiyan
- Chmielak Zbigniew
- Chouchane Iman
- Chung Eugene
- Cid Maria Cristina Schnettler
- Civitello Andrew
- Clark Andrew
- Cleland John G.F.
- Clifford Piers
- Coletti Andrew
- Collins John
- Colque Roberto
- Constance Christian
- Contreras Johanna
- Corbalan Ramon
- Corbalan Ramon
- Correa Luis Eduardo Echeverria
- Corredor Miguel Alfredo Moncada
- Cosansu Kahraman
- CostaâVitali Atilio
- Cotarlan Vladimir
- Coufal Zdenek
- Cox Jeremy
- CrespoâLeiro Maria G.
- Cruz Kimberly
- Cubero Javier Segovia
- Cui Hanbin
- Cymerman Krzysztof
- Dahlström Ulf
- Damy Thibaud
- Dauber Ira
- De Geeter Guillaume
- De los Rios Ibarra Manuel Odin
- De Pasquale Carmine
- Decoulx Eric
- Demir Mesut
- Desai Pratik
- Diaz Rafael
- Diaz Rafael
- Diaz Victor Alfonso Jimenez
- Dib Nabil
- Diez Mirta
- Dimov Bojidar
- Doblas Juan Jose Gomez
- Doi Masayuki
- Domae Hiroshi
- Donal Erwan
- Dong Yugang
- Donnelly Patrick
- Dorobantu Maria
- Dovgolis Svetlana
- Doyle Timothy
- Drexel Heinz
- Dronov Dmitry
- Droogne Walter
- Drozdz Jaroslaw
- Duarte Tatiana
- Duengen HansâDirk
- Dujardin Karl
- Dupont Matthias
- Duran Ruben Omar Garcia
- Duzenli Mehmet
- Dzupina Andrej
- Eaton Charles
- Ebato Mio
- Ebelt Henning
- Eberly Arthur
- Ebner Christian
- Echeverria Correa Luis E.
- Elliott James
- Elmahi Einas
- Elvan Arif
- Esperon Guillermo Antonio Llamas
- Ezekowitz Justin
- Ezhov Marat
- Fang James
- Fang James C.
- Farris Neil
- Feitell Scott
- Felker G. Michael
- Fernandez Alberto
- Fernando Ronald
- Ferraz Almir
- Figal Domingo Andres Pascual
- Filho Otavio Coelho
- Filho Pedro Pimentel
- Filippatos Gerasimos
- Fisher Daniel
- Florea Viorel
- Flores Ana Maria De Leon
- Floresta Agata Marina
- Fonseca Candida
- Fonseca CĂąndida
- Forman Steven
- Forster Tamas
- Fortes Jose Augusto Ribas
- Fourie Nyda
- Franchi Francesco
- Frank Theodore
- Frankenstein Lutz
- Freire Ramon Bover
- Fremont Richard
- French John
- Friedman Keith
- Frigerio Maria
- Friz Hernan Emilio Francisco Polo
- Fu Xin
- Fucili Alessandro
- Fuente Galan Luis
- Fuente Ricardo Alfonso Leon
- Fujii Kenshi
- Fujii Shigeru
- Fujiwara Wakaya
- Fukuzawa Shigeru
- Fulop Peter
- Gabriel George
- Gajardo Victor Areli Saavedra
- Galinier Michel
- Ganeshram Vedampattu
- Ganji Jagadeesh
- Garrido Marcelo Alejandro
- Gass Alan
- Gaudet Daniel
- Geltman Edward
- Gemignani Anthony
- GenthâZotz Sabine
- Georges JeanâLouis
- Giamouzis Grigorios
- Gianfagna Robert
- Giannetti Nadia
- Gilmore Richard
- Giorgeto Flavio Eduardo
- Giraldo Clara Ines Saldarriaga
- Giuca Alina
- Giudici Vittorio
- Glover Jason
- Gogia Harinder
- Gohara Seiichiro
- Gola Zbigniew
- Goloshchekin Boris
- Goncalvesova Eva
- Goncalvesova Eva
- Goncharov Ivan
- Gonsorcik Jozef
- Gonzalez Ricardo Garcia
- Gonzalez Salvador Leon
- Gordon Brian
- Gorodeski Eiran
- Gottlieb Stephen
- Goudev Assen
- Goudev Assen R.
- Gray Wayne
- Grazette Luanda
- Greco Oswaldo
- Grewal Gurinder
- Groote Pascal De
- Gueffet JeanâPierre
- Guerrero Rodolfo Andres Ahuad
- Gupta Dinesh
- Gupta Milan
- Guray Umit
- Haddad Tariq
- Haehling Stephan
- Hajko Erik
- Hal John
- Halpern Stephen
- Hametz Craig
- Hamilton Andrew
- Han Qinghua
- Han Yajun
- Handel Franklin
- Hara Hisao
- Harris John
- Hart Hamish
- Hart Terence
- Hartleib Michael
- Hasni Syed
- Hata Yoshiki
- Hattler Brack
- Hearne Steven
- Hedgepeth Chester
- Heilman Karl
- Heitner John
- Henderson David
- Herczeg Bela
- Hermans Walter
- Herzog William
- Hidaka Takayuki
- Hidalgo Mario Yanez
- Higashino Yorihiko
- Hiroi Shitoshi
- Hominal Miguel Angel
- Horacek Thomas
- Houra Marek
- Houston Brian
- Howlett Jonathan G.
- Huang He
- Huber Kurt
- Huelsmann Martin
- Hullin Roger
- Hunter Vernon
- Huynh Thao
- Ibañez Julio
- Ibrahim Hassan
- Indolfi Ciro
- Inomata Takayuki
- Iseki Harukazu
- Ishikawa Masahiro
- Isnard Richard
- Isshiki Takaaki
- Itchhaporia Dipti
- Ito Hiroshi
- Jackson Bruce
- Jacob Binu
- Jadbabaie Farid
- Jaeger Cristiano Pederneiras
- Jaffrani Naseem
- Jalaf Margarita Gertrudis Vejar
- Janik Matthew
- Jankowski Piotr
- Janmohamed Munir
- Jarasuniene Dalia
- Jattin Fernando Manzur
- Javier Julian
- Jeppesen Jorgen
- Jerabek Ondrej
- Jimenez Juan Francisco Delgado
- Jofre Christian Paolo Pincetti
- Jondeau Guillaume
- Jones Alonzo
- Joseph Susan
- Juanatey Jose Ramon Gonzalez
- Judkins Christopher
- Kadel Christoph
- Kadokami Toshiaki
- Kafara Mariusz
- Kai Hisashi
- KaiserâNielsen Peter
- Kajinami Kouji
- Kalarus Zbigniew
- KalecinskaâKrystkiewicz Ewa
- Kalra Paul
- Kaluski Edo
- Kanda Junji
- Kania Grzegorz
- Kao John
- Karavidas Apostolos
- Karim Amin
- Karlstrom Patric
- Karpenko Oleksandr
- Karvounis Haralambos
- Kasai Toshio
- Kassiotis Christos
- Katz Richard
- Kawakami Hideo
- Kawamitsu Katsunori
- Kawasaki Tomohiro
- Kazemi Navid
- Kazinczy Rita
- Kearney Leighton
- Keeling Philip
- Kellnerova Ivana
- Khalife Wissam
- Kida Keisuke
- Killat Holger
- Kindel Carlos Conejeros
- King Anthony
- Kirma Cevat
- Kitaoka Hiroaki
- Klimsa Zdenek
- Klug Eric
- Kobalava Zhanna
- Kochiadakis George
- Koga Tokushi
- Koike Akihiro
- Koizumi Tomomi
- Koldas Zehra Lale
- Koleckar Pavel
- Komiyama Nobuyuki
- Kondo Nicholas
- Konieczynska Malgorzata
- Kono Alan
- Koo Charles
- Kopaczewski Jerzy
- Korczyk Dariusz
- Koren Michael
- Korzh Oleksii
- Kosmacheva Elena
- Kostenko Viktor
- Kotelnikov Mikhail
- Kowalski Robert
- Kracz Igor
- Krantz Mori
- Krishnamoorthy Arun
- Krupicka Jiri
- Kryza Radim
- Kubota Toru
- Kulibaba Elena
- Kulynych Oleksii
- Kurtz Christopher E.
- Kwan Michael
- Lader Ellis
- Lakatos Ferenc
- Lakshminarayanan Batlagundu
- Lancellotti Patrizio
- Lanfear David E.
- Lang Chim
- Lang Christopher
- Laperche Thierry
- Laszlo Zoltan
- Leaes Paulo Ernesto
- Lefebvre JeanâMarie
- Legg Jason C.
- Leiro Maria Generosa Crespo
- Lelonek Malgorzata
- Lenartowska Lucyna
- Lenner Egon
- Leon Jose Luis Arenas
- Leonardi Sergio
- Lepor Norman
- LeWinter Martin
- Lewis Neil
- Li Dongye
- Li Jianjun
- Li Tianfa
- Li Weimin
- Li Yinjun
- Li Zhangquan
- Li Zhaoping
- Lighezan Daniel
- Lindholm CarlâJohan
- Linssen Gerardus
- Liu Feng
- Llamas Edmundo Alfredo Bayram
- Llerena Sara
- Lohr Nicole
- Londono Juan
- Lopez Gabriel Arturo Ramos
- Lopez Luis Horacio Atehortua
- Lopez Rodrigo Botero
- Lovell Charles
- Ludman Andrew
- Luengas Carlos Alberto
- Lukacova Jana
- Lukyanov Yury
- Lund Marianne
- Lund Mayanna
- Lupkovics Geza
- Lupovitch Steven
- Luquez Hugo
- Lymar Yurii
- Lynch Mary
- Ma Shumei
- Macarie CezarâEugen
- Macdonald Peter
- Macdonald Peter
- Machado Gustavo Francisco Mendez
- Machova Vilma
- Macias Leonardo
- Mackinnon Ignacio
- Maejima Yasuhiro
- Magro Michael
- Mahemuti Ailiman
- Mahmood Shahid
- Maia Lilia Nigro
- Majercak Ivan
- Majul Claudio Rodolfo
- Malhotra Sanjay
- Malhotra Vinay
- Malik Adnan
- Malik Fady I.
- Mamdani Shafiq
- Mancini Donna
- Manenti Euler Roberto Fernandes
- Manita Mamoru
- Manolis Athanasios
- Mantas Ioannis
- Mareev Vyacheslav
- Mareev Vyacheslav
- Margoczy Roman
- Margonato Alberto
- Mark Laszlo
- Marquez Lilia Luz Lobo
- Martindale Jeffrey
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- Martinez Laura Jordan
- Martinez Luis
- MartinezâArraras Joaquin
- MartinezâCastrillon Melvin
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- Masuda Seigo
- Matsumoto Takashi
- Mayer Nolan
- Mayoral Alejandro Recio
- McGrew Frank
- McKelvie Robert
- McKenzie Scott
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- McMurray John J.V.
- Menck Niels
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- Merkely Bela
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- Metra Marco
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- Mi Yafei
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- Miekus Pawel
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- Oliveira Luis
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- Parkhomenko Oleksandr
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- Paya Vicente Eduardo Climent
- Peart Brenda
- Peiro Maria Teresa Blasco
- Pelaez Sebastian Velez
- Perez Sonia Mirabet
- Perna Eduardo
- Perna Gianpiero
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- Suter Thomas M.
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- Teerlink John R.
- Terasaki Toshiro
- Terasawa Akihiro
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- Timofeev Alexander
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- Tocchetti Carlo Gabriele
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- Tomcsanyi Janos
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- Trebacz Jaroslaw
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- Vandekerckhove Hans
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- Vazquez Eduardo Salcido
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- Videbaek Lars
- Vidotti Maria Helena
- Vijay Nampalli
- Vilamajo Oscar Alberto Gomez
- Vilchez Francisco Gonzalez
- Villani Giovanni Quinto
- Villoch Mario
- Villota Julio Eduardo Nuñez
- Vinanska Daniela
- Vincenzi Antonella
- Vinereanu Dragos
- Vinereanu Dragos
- Vishnevsky Alexander
- Voevoda Mikhail
- Vogel Daniel
- Voicu OlgaâCristina
- Volterrani Maurizio
- Voors Adriaan
- Voors Adriaan A.
- Voronkov Leonid
- Vraa Soren
- Wada Atsuyuki
- Wahid Faisal
- Wal Ruud
- Wang Yi
- Wang Zhifang
- Watanabe Naoki
- Wei Yu
- Weir Robin
- Westenfeld Ralf
- Wheeler Matthew
- Whellan David
- Wiggers Henrik
- Wilkett Matt
- Willems Frank
- Williams Celeste
- Wlodarczyk Aleksander
- Wodlin Peter
- Wong Kenneth
- WozakowskaâKaplon Beata
- Wu Weiheng
- Yagensky Andriy
- Yamamoto Mitsutaka
- Yan Jing
- Yang Ping
- Yang Xuming
- Yang Zhenyu
- Yeoman Gary
- Yigit Zerrin
- Yilmaz Mehmet B.
- Yoshida Takeshi
- Yoshikawa Masaki
- Yousuf Kabir
- Yuan Zuyi
- Yuge Masaru
- Zabowka Maciej
- Zaca Valerio
- Zaidman Cesar
- Zanetti Fernando Tomas Lanas
- Zannad Faiez
- Zapata Gerardo
- Zdrenghea Dumitru
- Zeman Kamil
- Zeymer Uwe
- Zhang Jinguo
- Zhang Lily
- Zhang Shouyan
- Zhang Xuelian
- Zhang Yuhui
- Zhang Yuqing
- Zheng Yang
- Zheng Zhe
- Zhou Changyong
- Zieroth Shelley
- Zilahi Zsolt
- Zimmet Hendrik
- Zolty Ronald
- Zrazhevskiy Konstantin
- Zwaan Coenraad
- Publication venue
- 'Wiley'
- Publication date
- 01/11/2020
- Field of study
Aims:
The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTICâHF) trial. Here we describe the baseline characteristics of participants in GALACTICâHF and how these compare with other contemporary trials.
Methods and Results:
Adults with established HFrEF, New York Heart Association functional class (NYHA)ââ„âII, EF â€35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokineticâguided dosing: 25, 37.5 or 50âmg bid). 8256 patients [male (79%), nonâwhite (22%), mean age 65âyears] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NTâproBNP 1971âpg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTICâHF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressureâ<â100âmmHg (n = 1127), estimated glomerular filtration rate <â30âmL/min/1.73 m2 (n = 528), and treated with sacubitrilâvalsartan at baseline (n = 1594).
Conclusions:
GALACTICâHF enrolled a wellâtreated, highârisk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation
Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure
- Author
- A Alan Chu
- A Shekhar Pandey
- Aaron Sverdlov
- Abbasi S. A.
- Abdallah Al Mohammad
- Abdul Al-Hesayen
- Adams K. F.
- Adnan Malik
- Adriaan Voors
- Adrian Shandling
- Agata Marina Floresta
- Ahmet Celik
- Ailiman Mahemuti
- Aize van der Sluis
- Akihiro Koike
- Akihiro Nakamura
- Akihiro Terasawa
- Alan Gass
- Alan Kono
- Alan Meholick
- Alberto Caccavo
- Alberto Cadena Bonfanti
- Alberto Esteban Bazzoni Ruiz
- Alberto Fernandez
- Alberto Margonato
- Aldo Prado
- Alejandro Recio Mayoral
- Aleksander Wlodarczyk
- Aleksandra Manolova
- Alessandro Fucili
- Alex Mauricio Villablanca Sepulveda
- Alexander Adler
- Alexander Bykov
- Alexander Parkhomenko
- Alexander Sherenkov
- Alexander Timofeev
- Alexander Vishnevsky
- Alexandr Schee
- Alexandra Arias Mendoza
- Alexandre Tognon
- Alexey Repin
- Alicia Contreras Rodriguez
- Alina Giuca
- Alisdair Ryding
- Alistair Begg
- Almir Ferraz
- Alonzo Jones
- Amal Muthumala
- Aman Amanullah
- Amarinder Bindra
- Amin Karim
- Amin Yehya
- Amit Shah
- Amrut Ambardekar
- Ana Maria De Leon Flores
- Anand I.
- Anays Santana Izquierdo
- Andras Papp
- Andre Artis
- Andrea Mortara
- Andrej Dzupina
- Andres Iñiguez Romo
- Andrew Boyle
- Andrew Civitello
- Andrew Clark
- Andrew Coletti
- Andrew Hamilton
- Andrew Ludman
- Andrew Sauer
- Andrew Sindone
- Andriy Yagensky
- Andrzej Rynkiewicz
- Aniko Papp
- Anil Shah
- Anna Paszczuk
- Anna Stankiewicz
- Anselmo Paulino Bordonava
- Anthony Gemignani
- Anthony King
- Antonella Vincenzi
- Antonio Juan Castro Fernandez
- Antonio Lara Padron
- Apostolos Karavidas
- Arias-Mendoza A.
- Arif Elvan
- Arman Postadzhiyan
- Armando Garcia Castillo
- Arnold Seto
- Arthur Eberly 3rd
- Arun Krishnamoorthy
- Arunima Misra
- Assad Mouhaffel
- Assen Goudev
- Athanasios Manolis
- Atilio Costa-Vitali
- Atsushi Hirayama
- Atsutoshi Takagi
- Atsuyuki Wada
- Attila Mohacsi
- Aurelio Ortiz
- Aysha Badat
- Badrinathan Chandrasekaran
- Balgit Chhokar
- Barbara Pisani
- Barna Szabo
- Barry Bertolet
- Barry H Greenberg
- Barry Uretsky
- Batlagundu Lakshminarayanan
- Beat Knusel
- Beata Wozakowska-Kaplon
- Beatriz Diaz Molina
- Bela Herczeg
- Bela Merkely
- Benjamin Trichon
- Bhola Rama
- Biering-Sorensen T.
- Binoy Skaria
- Binu Jacob
- Bohm M.
- Bojidar Dimov
- Bonderman D.
- Boris Goloshchekin
- Bozena Sobkowicz
- Brack Hattler
- Bradley Weinberg
- Brenda Lemus
- Brenda Peart
- Brian Bostick
- Brian Claggett
- Brian Gordon
- Brian Houston
- Bruce Jackson
- Bruce Sussex
- Bruno Paolino
- Candida Fonseca
- Carl-Johan Lindholm
- Carlo Gabriele Tocchetti
- Carlos Alberto Luengas
- Carlos Arrieta Garcia
- Carlos Conejeros Kindel
- Carlos Poy
- Carmine De Pasquale
- Carol Davila
- Carsten Schmalfuss
- Celeste Williams
- Cesar Zaidman
- Cevat Kirma
- CezarEugen Macarie
- Changyong Zhou
- Charles Eaton
- Charles Koo
- Charles Lovell
- Charles Treasure
- Chavdar Velikov
- Chester Hedgepeth
- Chiara Melloni
- Chim Lang
- Christian Constance
- Christian Ebner
- Christian Mueller
- Christian Paolo Pincetti Jofre
- Christoph Kadel
- Christopher E Kurtz
- Christopher Judkins
- Christopher Lang
- Christopher Pickett
- Christopher Rowan
- Christopher Vaccari
- Christos Kassiotis
- Ciro Indolfi
- Claire Varin
- Clara Ines Saldarriaga Giraldo
- Claudia Raineri
- Claudio Bilato
- Claudio Cavallini
- Claudio Rodolfo Majul
- Cleland J. G. F.
- Coenraad van der Zwaan
- Constantin Militaru
- Corbalan R.
- Craig Barr
- Craig Hametz
- Crespo-Leiro M. G.
- Cristian Gheorghe Podoleanu
- Cristiano Pederneiras Jaeger
- Cristina Danila
- Csaba Salamon
- Dahlstrom U.
- Dalia Jarasuniene
- Dallas Price
- Dalton McLean
- Daniel Aradi
- Daniel Beug
- Daniel Fisher
- Daniel Gaudet
- Daniel Lenihan
- Daniel Lighezan
- Daniel Pauly
- Daniel Savard
- Daniel Vogel
- Daniela Garcia Brasca
- Daniela Pini
- Daniela Vinanska
- Dariusz Korczyk
- David Chang
- David F Kong
- David Henderson
- David Lanfear
- David Murray
- David Rawitscher
- David Schultz
- David Stepek
- David Whellan
- Debashis Roy
- Deddo Moertl
- Denis-Carl Phaneuf
- Dennis Rupka
- Deovrat Singh
- Devesh Patel
- Diana Bonderman
- Diaz R.
- Diego Alejandro Besada
- Diego Felipe Martinez
- Dimitrios Tziakas
- Dinesh Gupta
- Dipti Itchhaporia
- Dirk Boswijk
- Dirk Lok
- Dirk Schellings
- Dmitriy Belenkiy
- Dmitry Dronov
- Dmytro Reshotko
- Domenico Bonaduce
- Domingo Andres Pascual Figal
- Dongye Li
- Donna Mancini
- Dora Ines Molina de Salazar
- Douglas Brinkley
- Douglas Martel
- Douglas Sawyer
- Dragos Vinereanu
- Driek Beelen
- Dulce Brito
- Dumitru Zdrenghea
- Echeverria L. E.
- Edmundo Alfredo Bayram Llamas
- Edo Kaluski
- Eduardo Perna
- Eduardo Salcido Vazquez
- Edward Geltman
- Edward Portnay
- Egon Lenner
- Eileen O'Meara
- Einas Elmahi
- Eiran Gorodeski
- Elena Cowan
- Elena Kosmacheva
- Elena Kulibaba
- Elena Shutemova
- Ellis Lader
- Elvin Kedhi
- Erberto Carluccio
- Eric Decoulx
- Eric Klug
- Erik Hajko
- Ersel Onrat
- Ertugrul Okuyan
- Erwan Donal
- Eugene Chung
- Eugene Joseph Bauerlein
- Euler Roberto Fernandes Manenti
- Eva Goncalvesova
- Eva Peterfai
- Ewa Kalecinska-Krystkiewicz
- Ewa Straburzynska-Migaj
- Fabiana Rollini
- Fabio Silveira
- Fady I Malik
- Faiez Zannad
- Faisal Wahid
- Fang J. C.
- Farid Jadbabaie
- Felice Achilli
- Felix Ramires
- Feng Liu
- Ferenc Lakatos
- Fernando Bacal
- Fernando Boccalandro
- Fernando Colombo Berra
- Fernando Manzur Jattin
- Fernando Soto Loureiro
- Fernando Tomas Lanas Zanetti
- Filipa Almeida
- Filippatos G.
- Flavio Brito
- Flavio Eduardo Giorgeto
- Florence Rothenberg
- Florin Mitu
- Fonseca C.
- Fragkiskos Parthenakis
- Francesco Franchi
- Francisco Gonzalez Vilchez
- Francois Roubille
- Frank McGrew
- Frank Smart
- Frank Willems
- Franklin Handel
- François Picard
- Freny Mody
- Friedrich Fruhwald
- Fumi Yamamoto
- G Michael Felker
- Gabriel Arturo Ramos Lopez
- Gabriela Stanciulescu
- Gabriele Jakl-Kotauschek
- Gaetano Maria De Ferrari
- Garth Vaz
- Gary Yeoman
- Gaurav Aggarwala
- Georg Noll
- George Gabriel
- George Kochiadakis
- George Marzouka
- George Sokos
- Georgi Todorov
- Georgiy Dzyak
- Georgy Arbolishvili
- Gerardo Zapata
- Gerardus Linssen
- Gerasimos Filippatos
- Gerhard Poelzl
- Geza Lupkovics
- Giancarlo Piovaccari
- Gianfranco Sinagra
- Gianpiero Perna
- Gilmar Reis
- Gintare Sakalyte
- Giovanni Geronilla
- Giovanni Quinto Villani
- Giuseppe Ambrosio
- Giuseppe Musumeci
- Glenn Hamroff
- Goncalvesova E.
- Gordon Moe
- Gordon Reeves
- Goudev A. R.
- Gregorio Sanchez Vallejo
- Gregory Sampognaro
- Gregory Szto
- Gregory Thomas
- Grigorios Giamouzis
- Grzegorz Kania
- Grzegorz Skonieczny
- Guillaume De Geeter
- Guillaume Jondeau
- Guillermo Antonio Llamas Esperon
- Guoqin Chen
- Gurinder Grewal
- Gurusher Panjrath
- Gustavo Francisco Mendez Machado
- Guy Proulx
- Gyula Szasz
- Hakima Bourhaial
- Hal Skopicki
- Hamish Hart
- Hanbin Cui
- Hans Vandekerckhove
- Hans-Dirk Duengen
- Haralambos Karvounis
- Harinder Gogia
- Harukazu Iseki
- Hassan Ibrahim
- He Huang
- Heinz Drexel
- Hendrik Zimmet
- Henning Ebelt
- Henricus Van Kesteren
- Henrik Wiggers
- Henry Dargie
- Henry Ooi
- Hernan Emilio Francisco Polo Friz
- Hideki Ueno
- Hideo Izawa
- Hideo Kawakami
- Hideyuki Tsuboi
- Hiroaki Kitaoka
- Hiroaki Kiyokawa
- Hiroki Uehara
- Hiroshi Asano
- Hiroshi Domae
- Hiroshi Ito
- Hiroshi Meno
- Hiroshi Sugino
- Hiroshi Takaishi
- Hiroyuki Kawata
- Hisao Hara
- Hisashi Kai
- Holger Killat
- Honarpour N.
- Horacio Alberto Avaca
- Howlett J. G.
- Hugo Luquez
- Huifang Tang
- Ian Buysschaert
- Ibrahim Haldun Muderrisoglu
- Ichiro Michishita
- Ignacio Mackinnon
- Igor Kraiz
- Igor Motylev
- Igor Vakaliuk
- Iman Chouchane
- Imre Szakal
- Inder Anand
- Inder Singh
- Ioannis Barbetseas
- Ioannis Mantas
- Ioannis Styliadis
- Ira Dauber
- Irina Osipova
- Irina Semenova
- Iurii Rudyk
- Ivan Goncharov
- Ivan Majercak
- Ivana Kellnerova
- Ivaylo Vasilev
- Ivo Petrov
- Ivo Podpera
- J Dedrick Jordan
- J Russell Strader
- Jacob Eifer Moller
- Jacob Van Eck
- Jadwiga Nessler
- Jagadeesh Ganji
- James Elliott
- James Fang
- James L Januzzi
- James Rider
- James Watts
- Jan Belohlavek
- Jan Stevlik
- Jana Lukacova
- Janka Skrobakova
- Janos Tomcsanyi
- Janusz Spyra
- Jaroslaw Drozdz
- Jaroslaw Trebacz
- Jason C Legg
- Jason Glover
- Jasper Trevelyan
- Javed Butler
- Javier Segovia Cubero
- Javier Vasallo
- Jean Etienne Ricci
- Jean-Louis Georges
- Jean-Marie Lefebvre
- Jean-Michel Tartiere
- Jean-Noel Trochu
- Jean-Pierre Gueffet
- Jeffrey Martindale
- Jelena Celutkiene
- Jenica N Upshaw
- Jennifer Cook
- Jens Taggeselle
- Jeremy Cox
- Jeroen Schaap
- Jerzy Kopaczewski
- Jianjun Li
- Jindrich Spinar
- Jing Li
- Jing Yan
- Jinguo Zhang
- Jiri Krupicka
- Jiyan Chen
- Joao Carlos Braga
- Joaquin Martinez-Arraras
- Johanna Contreras
- Johannes Remmen
- John Amerena
- John Andrew Morrow
- John Atherton
- John Beltrame
- John Boehmer
- John Cleland
- John Collins
- John Corbelli
- John French
- John Groarke
- John Harris
- John Heitner
- John J V McMurray
- John Kao
- John Mignone
- John Murray
- John Parissis
- John van Hal
- Jolita Badariene
- Jonathan Howlett
- Jooyoung Shin
- Jorge Cheirif
- Jorge Leonardo Cobos Segarra
- Jorge Roberto Aiub
- Jorgen Jeppesen
- Jose Alfredo Pagola Carrasco
- Jose Augusto Ribas Fortes
- Jose Cardona
- Jose Francisco Saraiva
- Jose Luis Accini Mendoza
- Jose Luis Arenas Leon
- Jose Luis Lambert Rodriguez
- Jose Maria Arizon Del Prado
- Jose Ramon Gonzalez Juanatey
- Joseph Massaro
- Joseph Radojevic
- Joseph Rahman
- Joshua Asubiaro
- Jozef Gonsorcik
- Juan Francisco Delgado Jimenez
- Juan Jose Gomez Doblas
- Juan Londono
- Juan Luis Bonilla Palomas
- Julian Alonso Coronel Arroyo
- Julian Javier
- Juliano Cardoso
- Julio Eduardo Nuñez Villota
- Julio Ibañez
- Julio Tallet
- Jun Tanabe
- Junji Kanda
- Justin Ezekowitz
- Justin Taylor
- Kabir Yousuf
- Kahraman Cosansu
- Kalman Toth
- Kamil Zeman
- Kaoru Okishige
- Karel Peterka
- Karel Sochor
- Karen P Alexander
- Karen Sliwa
- Karl Dujardin
- Karl Heilman
- Katalin Bezzegh
- Katerina Naka
- Katsunori Kawamitsu
- Kazuhisa Mitsuo
- Keiji Ujino
- Keijiro Saku
- Keisuke Kida
- Keith Aaronson
- Keith Friedman
- Kenji Ando
- Kenji Onoue
- Kenneth Wong
- Kenshi Fujii
- Kentaro Nakamura
- Keyur Shah
- Kimberly Cruz
- Kimiaki Nagase
- Kirkwood Adams
- Klemens Ablasser
- Kodangudi Ramanathan
- Koichi Node
- Koichiro Sugimura
- Konstantin Zrazhevskiy
- Konstantinos Tsioufis
- Kotaro Numaguchi
- Kouji Kajinami
- Krzysztof Cymerman
- Kumiko Nakayama
- Kunihiko Makino
- Kurt Boman
- Kurt Huber
- Kurtz C. E. GALACTIC-HF Investigators: John R Teerlink
- Ladislav Busak
- Lana Tsao
- Lanfear D. E.
- Larry Allen
- Lars Videbaek
- Larysa Mishchenko
- Larysa Vasilyeva
- Laszlo Mark
- Laszlo Nagy
- Laura Jordan Martinez
- Laurie Letarte
- Lawrence Galitz
- Lawrence J Lesko
- Legg J. C.
- Leighton Kearney
- Lenka Spinarova
- Leonard Pianko
- Leonardo Macias
- Leonardo Novaretto
- Leonid Pimenov
- Leonid Rudenko
- Leonid Voronkov
- Leopoldo Soares Piegas
- Lesley Burgess
- Lesya Rasputina
- Li J.
- Libor Nechvatal
- Lidia Ana Zytynski Moura
- Lidia Pawlowicz
- Lilia Luz Lobo Marquez
- Lilia Nigro Maia
- Lilia Schiavi
- Liliana Nicolosi
- Lily Zhang
- Lisa Mielniczuk
- Liudmyla Alieksieieva
- Lixin Jiang
- Llyod Stahl
- Lokesh Chandra
- Louis Van Zyl
- Luanda Grazette
- Lubomir Antalik
- Luc Pierard
- Lucie Sharpsten
- Lucyna Lenartowska
- Luis Almenar Bonet
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- Voors A. A.
- Vyacheslav Mareev
- Vyacheslav Ryabov
- W Schuyler Jones
- Wael AboAuda
- Wakaya Fujiwara
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- Wayne Gray
- Weiheng Wu
- Weimar Kunz Barroso de Souza
- Weimin Li
- Wentang Niu
- Wilder Castaño Osorio
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- William Nelson
- William Randall
- Wissam Khalife
- Xin Fu
- Xuelian Zhang
- Xuming Yang
- Yafei Mi
- Yajun Han
- Yang Zheng
- Yanling Qu
- Yann Rosamel
- Yasuchika Takeishi
- Yasuhiro Maejima
- Yasuki Kihara
- Yasunori Ueda
- Yasuo Okumura
- Yasushi Sakata
- Yevgeniya Svishchenko
- Yi Wang
- Yilmaz M. B.
- Yinjun Li
- Yorihiko Higashino
- Yoshihiko Saito
- Yoshiki Hata
- Yoshinori Yasaka
- Yoshitoshi Urabe
- Yu Wei
- Yuemin Sun
- Yugang Dong
- Yuhui Zhang
- Yuji Nakazato
- Yukihiko Momiyama
- Yukihito Sato
- Yukiko Morita
- Yuksel Cavusoglu
- Yuqing Zhang
- Yurii Lymar
- Yuriy Mostovoy
- Yury Lukyanov
- Yury Shvarts
- Yutaka Akatsuka
- Yves Pesant
- Zannad F.
- Zbigniew Bednarkiewicz
- Zbigniew Chmielak
- Zbigniew Gola
- Zbigniew Kalarus
- Zbigniew Pijanowski
- Zbynek Pozdisek
- Zdenek Coufal
- Zdenek Klimsa
- Zdenek Monhart
- Zehra Lale Koldas
- Zerrin Yigit
- Zhanna Kobalava
- Zhanquan Li
- Zhaoping Li
- Zhe Zheng
- Zhenyu Yang
- Zhifang Wang
- Zoltan Laszlo
- Zsolt Zilahi
- Zuyi Yuan
- Zuzana Motovska
- Publication venue
- 'Massachusetts Medical Society'
- Publication date
- 01/01/2021
- Field of study
BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016 -002299-28.)