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23 results on '"Timo Lenderink"'

1. Relation of Iron Status to Prognosis After Acute Coronary Syndrome

Author

Muhammed T. Gürgöze, Isabella Kardys, K. Martijn Akkerhuis, Rohit M. Oemrawsingh, Hilde E. Groot, Pim van der Harst, Victor A. Umans, Bas Kietselaer, Eelko Ronner, Timo Lenderink, Folkert W. Asselbergs, Olivier C. Manintveld, Eric Boersma, Cardiology, Cardiovascular Centre (CVC), RS: Carim - H01 Clinical atrial fibrillation, Cardiologie, and MUMC+: MA Med Staf Spec Cardiologie (9)

Subjects
Male, MEDICAL PROGRESS, RISK, DISORDERS, Iron, Transferrin, Iron Deficiencies, Middle Aged, Prognosis, DIAGNOSIS, BINDING-CAPACITY, DEFICIENCY, MYOCARDIAL-INFARCTION, Ferritins, Humans, HEART-FAILURE, Female, Prospective Studies, Acute Coronary Syndrome, Cardiology and Cardiovascular Medicine, Biomarkers
Abstract

Iron deficiency has been extensively researched and is associated with adverse outcomes in heart failure. However, to our knowledge, the temporal evolution of iron status has not been previously investigated in patients with acute coronary syndrome (ACS). Therefore, we aimed to explore the temporal pattern of repeatedly measured iron, ferritin, transferrin, and transferrin saturation (TSAT) in relation to prognosis post-ACS. BIOMArCS (BIOMarker study to identify the Acute risk of a Coronary Syndrome) is a prospective, multicenter, observational cohort study conducted in The Netherlands between 2008 and 2015. A total of 844 patients with post-ACS were enrolled and underwent high-frequency (median 17) blood sampling during 1 year follow-up. Biomarkers of iron status were measured batchwise in a central laboratory. We analyzed 3 patient subsets, including the case-cohort (n = 187). The primary endpoint (PE) was a composite of cardiovascular mortality and repeat nonfatal ACS, including unstable angina pectoris requiring revascularization. The association between iron status and the PE was analyzed using multivariable joint models. Mean age was 63 years; 78% were men, and >50% had iron deficiency at first sample in the case-cohort. After adjustment for a broad range of clinical variables, 1 SD decrease in log-iron was associated with a 2.2-fold greater risk of the PE (hazard ratio 2.19, 95% confidence interval 1.34 to 3.54, p = 0.002). Similarly, 1 SD decrease in log-TSAT was associated with a 78% increased risk of the PE (hazard ratio 1.78, 95% confidence interval 1.17 to 2.65, p = 0.006). Ferritin and transferrin were not associated with the PE. Repeated measurements of iron and TSAT predict risk of adverse outcomes in patients with post-ACS during 1 year follow-up. Trial Registration: The Netherlands Trial Register. Unique identifiers: NTR1698 and NTR1106. Registered at https://www.trialregister.nl/trial/1614 and https://www.trialregister.nl/trial/1073.

Published
2022

2. Icosapent Ethyl Reduces Ischemic Events in Patients With a History of Previous Coronary Artery Bypass Grafting: REDUCE-IT CABG

Author

Subodh Verma, Deepak L. Bhatt, Ph. Gabriel Steg, Michael Miller, Eliot A. Brinton, Terry A. Jacobson, Nitish K. Dhingra, Steven B. Ketchum, Rebecca A. Juliano, Lixia Jiao, Ralph T. Doyle, Craig Granowitz, C. Michael Gibson, Duane Pinto, Robert P. Giugliano, Matthew J. Budoff, R. Preston Mason, Jean-Claude Tardif, Christie M. Ballantyne, Fabrice M.A.C. Martens, Astrid Schut, Brian Olshansky, Mina Chung, Al Hallstrom, Lesly Pearce, Cyrus Mehta, Rajat Mukherjee, Anjan K. Chakrabarti, Eli V. Gelfand, Megan Carroll Leary, Duane S. Pinto, Yuri B. Pride, Steven Ketchum, Ramakrishna Bhavanthula, Gertrude Chester, Christina Copland, Katelyn Diffin, Ralph Doyle, Kurt Erz, Alex Giaquinto, Paula Glanton, Angela Granger, Richard H. Iroudayassamy, Rebecca Juliano, James Jin, Dimitry Klevak, Hardik Panchal, Robert Wang, Shin-Ru Wang, Gerard Abate, Peggy J. Berry, Rene Braeckman, Declan Doogan, Anne Elson, Amy HauptmannBaker, Isabel Lamela, Catherine Lubeck, Mehar Manku, Sabina Murphy, Monica Sanford, William Stirtan, Paresh Soni, Arnaud Bastien, Demetria Foster, Evangelito Gascon, Judith Johnson, Lasbert Latona, Gang Liu, Sandra Palleja, Nelly Sanjuan, Jimmy Shi, William Stager, Mukund Venkatakrishnan, Ahmed Youssef-Agha, Julie Zhu, Leela Aertker, Suresh Ankolekar, Lisa Goldberg, Natasa Rajicic, Jianfen Shu, Heng Zou, Magdy Mikhail, Gamil Dawood, N. Mathew Koshy, Sandip K. Mukherjee, Rafik Abadier, Andrea L. Lawless, William P. McGuinn, Howard Weintraub, Kathryn Rohr, Edmund Claxton, Robert J. Weiss, Terry D. Klein, Mani Nallasivan, Stephen Crowley, Marilyn King, Anthony D. Alfieri, David Fitz-Patrick, Irving Loh, Nolan J. Mayer, Rakesh Prashad, Samuel Lederman, Debra Weinstein, Harold E. Bays, Keith Chu, Alireza Maghsoudi, Paul D. Thompson, Jeff Carstens, Anna Chang, Kenneth R. Cohen, Julius Dean, Howard S. Ellison, Bernard Erickson, Enrique A. Flores, Daniel W. Gottlieb, Paul Grena, John R. Guyton, Peter H. Jones, John M. Joseph, Norman E. Lepor, Sam Lerman, Robert D. Matheney, Theodore R. Pacheco, Michael B. Russo, John Rubino, Edward S. Pereira, Albert A. Seals, Eduardo Viera, Alan D. Steljes, Jason Thompson, Shaival Kapadia, Michael McIvor, Jorge E. Salazar, Jose O. Santiago, Ralph Vicari, Martin R. Berk, William A. Kaye, Marcus McKenzie, David Podlecki, Brian D. Snyder, Stephen Nash, David M. Herrington, Wallace Johnson, Joseph R. Lee, Ronald Blonder, Alpa M. Patel, Ramon Castello, Susan Greco, Dean J. Kereiakes, Venkatesh K. Nadar, Mark Nathan, Ranganatha P. Potu, Robert Sangrigoli, Richard Smalling, Mitchell Davis, Robert Braastad, James McCriskin, Kunal Bodiwala, Joe L. Hargrove, Mark W. Graves, George Emlein, Raegan W. Durant, James W. Clower, Rohit Arora, Narendra Singh, Lisa Warsinger Martin, W Herbert Haught, Marc P. Litt, Michael D. Klein, Peter Hoagland, Michael Goldstein, Marco S. Mazzella, Daniel H. Dunker, Brian H. Kahn, Carlos S. Ince, Frank A. McGrew, Jay Lee, David Pan, Salman A. Khan, Uri Elkayam, Wasim Deeb, Anne C. Goldberg, Christopher S. Brown, Wayne N. Leimbach, Thomas S. Backer, David R. Sutton, Joel Gellman, Anu R. George, Alan S. Hoffman, Mark Kates, Kishlay Anand, Robert Bear, Brendan J. Cavanaugh, Ramon G. Reyes, Rodolfo Sotolongo, Kenneth Sabatino, Kevin Gallagher, Ehab Sorial, Chris Geohas, Kathleen E. Magness, Bernard P. Grunstra, Frederik A. Martin, William S. Knapp, Mel E. Lucas, John J. Champlin, Jason Demattia, Patrick H. Peters, Judith Kirstein, William J. Randall, Cezar S. Staniloae, Jennifer G. Robinson, Alexander Adler, Christopher Case, Andrew J. Kaplan, Gregory F. Lakin, Krishan K. Goyle, Michael J. DiGiovanna, Chester L. Fisher, Michael Lillestol, Michael Robinson, Robert G. Perry, Lawrence S. Levinson, Brian G. Everhart, Robert D. Madder, Earl F. Martin, Earl E. Martin, Imtiaz Alam, Jose Mari L. Elacion, Robina Poonawala, Taddese T. Desta, Jerome A. Robinson, Gilbert J. Martinez, Jakkidi S. Reddy, Jeffrey D. Wayne, Samuel Mujica Trenche, Westbrook I. Kaplan, Rubin H. Saavedra, Michael D. DiGregorio, Barry D. Bertolet, Neil J. Fraser, Terence T. Hart, Ronald J. Graf, David A. Jasper, Michael Dunn, Dan A. Streja, David J. Strobl, Nan Jiang, Vicki Kalen, Richard Mascolo, Mercedes B. Samson, Michael Stephens, Bret M. Bellard, Mario Juarez, Patrick J. McCarthy, John B. Checton, Michael Stillabower, Edward Goldenberg, Amin H. Karim, Naseem Jaffrani, Robert C. Touchon, Erich R. Fruehling, Clayton J. Friesen, Pradipta Chaudhuri, Frank H. Morris, Robert E. Broker, Rajesh J. Patel, Susan Hole, Randall P. Miller, Francisco G. Miranda, Sadia Dar, Shawn N. Gentry, Paul Hermany, Charles B. Treasure, Miguel E. Trevino, Raimundo Acosta, Anthony Japour, Samuel J. Durr, Thomas Wang, Om P. Ganda, Perry Krichmar, James L. Arter, Douglas Jacoby, Michael A. Schwartz, Amer Al-Karadsheh, Nelson E. Gencheff, John A. Pasquini, Richard Dunbar, Sarah Kohnstamm, Hector F. Lozano, Francine K. Welty, Thomas L. Pitts, Brian Zehnder, Salah El Hafi, Mark A. King, Arnold Ghitis, Marwan M. Bahu, Hooman Ranjbaran Jahromi, Ronald P. Caputo, Robert S. Busch, Michael D. Shapiro, Suhail Zavaro, Munib Daudjee, Shahram Jacobs, Vipul B. Shah, Frank Rubalcava, Mohsin T. Alhaddad, Henry Lui, Raj T. Rajan, Fadi E. Saba, Mahendra Pai N Gunapooti, Tshiswaka B. Kayembe, Timothy Jennings, Robert A. Strzinek, Michael H. Shanik, Pradeep K. Singh, Alastair C. Kennedy, Howard Rubenstein, Ramin Manshadi, Joanne Ladner, Lily Kakish, Ashley Kakish, Amy L. Little, Jaime Gerber, Nancy J. Hinchion, Janet Guarino, Denise Raychok, Susan Budzinski, Kathleen Kelley-Garvin, April Beckord, Jessica Schlinder, Arthur Schwartzbard, Stanley Cobos, Deborah Freeman, David Abisalih, Dervilla McCann, Kylie Guy, Jennifer Chase, Stacey Samuelson, Madeline Cassidy, Marissa Tardif, Jaime Smith, Brenna Sprout, Nanette Riedeman, Julie Goza, Lori Johnson, Chad Kraske, Sheila Hastings, Chris Dutka, Stephanie Smith, Toni McCabe, Kathleen Maloney, Paul Alfieri, Vinay Hosemane, Chanhsamone Syravanh, Cindy Pau, April Limcoiloc, Tabitha Carreira, Taryn S. Kurosawa, Razmig Krumian, Krista Preston, Ashraf Nashed, Daria Schneidman-Fernandez, Jack Patterson, John Tsakonas, Jennifer Esaki, Lynn Sprafka, Porous Patel, Brian Mitchell, Erin M. Ross, Donna Miller, Akash Prashad, Kristina M. Feyler, Natasha Juarbe, Sandra Herrera, Sarah M. Keiran, Becky Whitehead, Whitney Asher, Coury Hobbs, Abbey Elie, Jean Brooks, Amanda L. Zaleski, Brenda Foxen, Barb Lapke, Philippa Wright, Bristol Pavol, Gwen Carangi, Marla Turner, Katharine W. Sanders, Rikita S. Delamar, Virginia L. Wilson, Sarah M. Harvel, Alison M. Cartledge, Kaitlyn R. Bailey, Kathleen Mahon, Timothy Schuchard, Jen Humbert, Mark C. Hanson, Michael P. Cecil, James S. Abraham, Lorie Benedict, Claudia Slayton, Curtis S. Burnett, Rachel W. Ono-Lim, Sharon Budzinski, Shubi A. Khan, Sharon Goss, Terry Techmanski, Farida Valliani, Rimla Joseph, Edith Flores, Laurn Contreras, Ana Aguillon, Carrie-Ann Silvia, Maria Martin, Edmund K. Kerut, Leslie W. Levenson, Louis B. Glade, Brian J. Cospolich, Maureen W. Stein, Stephen P. LaGuardia, Thelma L. Sonza, Tracy M. Fife, Melissa Forschler, Jasmyne Watts, Judy Fritsch, Emese Futchko, Sarah Utech, Scott B. Baker, Miguel F. Roura, Scott A. Segel, James S. Magee, Cathy Jackson, Rebecca F. Goldfaden, Liudmila Quas, Elizabeth C. Ortiz, Michael Simpson, Robert Foster, Christopher Brian, James Trimm, Michael Bailey, Brian Snoddy, Van Reeder, Rachel Wilkinson, Harold Settle, Cynthia Massey, Angela Maiola, Michele Hall, Shelly Hall, Wanda Hall, Mark Xenakis, Janet Barrett, Giovanni Campanile, David Anthou, Susan F. Neill, Steven Karas, Enrique Polanco, Norberto Schechtman, Grace Tischner, Kay Warren, Cynthia St Cyr, Menna Kuczinski, Latrina Alexander, Maricruz Ibarra, Barry S. Horowitz, Jaime Steinsapir, Jeanette Mangual-Coughlin, Brittany Mooney, Precilia Vasquez, Kathleen Rodkey, Alexandria Biberstein, Christine Ignacio, Irina Robinson, Marcia Hibberd, Lisa B. Hoffman, Daniel J. Murak, Raghupathy Varavenkataraman, Theresa M. Ohlson Elliott, Linda A. Cunningham, Heather L. Palmerton, Sheri Poole, Jeannine Moore, Helene Wallace, Ted Chandler, Robert Riley, Farah Dawood, Amir Azeem, Michael Cammarata, Ashleigh Owen, Shivani Aggarwal, Waqas Qureshi, Mohamed Almahmoud, Abdullahi Oseni, Adam Leigh, Erin Barnes, Adam Pflum, Amer Aladin, Karen Blinson, Vickie Wayne, Lynda Doomy, Michele Wall, Valerie Bitterman, Cindi Young, Rachel Grice, Lioubov Poliakova, Jorge Davalos, David Rosenbaum, Mark Boulware, Heather Mazzola, J. Russell Strader, Russell Linsky, David Schwartz, Elizabeth Graf, Alicia Gneiting, Melissa Palmblad, Ashley Donlin, Emily Ensminger, Hillary Garcia, Dawn Robinson, Carolyn Tran, Jeffrey Jacqmein, Darlene Bartilucci, Michael Koren, Barbara Maluchnik, Melissa Parks, Jennifer Miller, Cynthia DeFosse, Albert B. Knouse, Amy Delancey, Stephanie Chin, Thomas Stephens, Mag Sohal, Juana Ingram, Swarooparani Kumar, Heather Foley, Nina Smith, Vera McKinney, Linda Schwarz, Judith Moore, Hildreth Vernon Anderson, Stefano Sdringola-Maranga, Ali Denktas, Elizabeth Turrentine, Rhonda Patterson, John Marshall, Terri Tolar, Donna Patrick, Pamela Schwartzkopf, Anthony M. Fletcher, Frances R. Harris, Sherry Clements, Tiffany Brown, William Smith, Stacey J. Baehl, Robin Fluty, Daniel VanHamersveld, Dennis Breen, Nancy Bender, Beverly Stafford, Tamika Washington, Margaret N. Pike, Mark A. Stich, Evyan Jawad, Amin Nadeem, Jill Nyland, Rhonda Hamer, Kendra Calhoun, Charlotte Mall, Samuel Cadogan, Kati Raynes, Richard Katz, Lorraine Marshall, Rashida Abbas, Jay L. Dinerman, John T. Hartley, Beth Lamb, Lisa Eskridge, Donna Raymond, Kristy Clemmer, Denise M. Fine, Paula Beardsley, Janet Werner, Bette Mahan, Courtney VanTol, Robert Herman, Christine Raiser-Vignola, Felicia McShan, Stefanie A. Neill, David R. Blick, Michael J. Liston, Denetta K. Nelson, Sandra K. Dorrell, Patricia Wyman, Ambereen Quraishi, Fernando Ferro, Frank Morris, Vicki J. Coombs, Autumn M. Mains, Austin A. Campbell, Jeanne Phelps, Cheryl A. Geary, Ellen G. Sheridan, Jean M. Downing, Arie Swatkowski, Tish Redden, Brian Dragutsky, Susan Thomas, Candace Mitchell, Diana Barker, Elanie Turcotte, Deborah Segerson, Jill Guy, Karena De La Mora, Jennifer Hong, Dennis Do, Rose Norris, Faisal Khan, Hector Montero, Stacy Kelly-White, Alan Cleland, Rosalyn Alcalde-Crawford, Melissa Morgan, Brijmohan Sarabu, Megan Minor, Shweta Kamat, Stephanie M. Estes, Nancee Harless, Alicia Disney, Jodi L. Pagano, Chad M. Alford, Noel W. Bedwell, Warren D. Hardy, Kevin DeAndrade, Jessica G. Elmore, Eric Auerbach, Anthony W. Haney, Miriam H. Brooks, Jose Torres, Lois Roper, Terry Backer, Katie Backer, John G. Evans, Ricardo A. Silva, Lorraine H. Dajani, Veronica Yousif, Tammy Ross, Sion K. Roy, Ronald Oudiz, Sajad Hamal, Ferdinand Flores, Amor Leahy, Debra Ayer, Swapna George, Chrisi Carine Stewart, Elvira Orellana, Cristina Boccalandro, Mary Rangel, Suzanne Hennings, Carl Vanselow, Teri Victor, Darlene Birdwell, Paul Haas, Anthony Sandoval, Gina Ciavarella, Caroline Saglam, Amy Bird, Keith Beck, Brian Poliquin, David Dominguez, Brittany Tenorio, Harvonya Perkins, Esther San Roman, Paris Bransford, Christy Lowrance, Marcy Broussard, Mary Ellis, Bobbi Skiles, Jessica Hamilton, Kathryn Hall, Diego Olvera, Julee A. Hartwell, Nevien Sorial, Mary Rickman, Kevin Berman, Nirav Mehta, Annie Laborin, Rodger Rothenberger, Sarah Beauvilliers, Kathy Morrell, Michael P. Schachter, Cindy L. Perkins, Elizabeth A. Gordon, Jennifer Lauer, Kim Bichsel, Kelly Oliver, Leslie J. Mellor, Candice Demattia, Jennifer Schomburg, Yenniffer Moreno, Eduardo Mansur-Garza, Lena Rippstein, Lorie Chacon, Andrea Pena, Michelle King, Susan Richardson, Annette Jessop, Nicole Tucker, Whitney Royer, Gilbert Templeton, Ann Moell, Christine Weller, Melissa J. Botts, Gretel Hollon, Elsa Homberg-Pinassi, Paula Forest, Aref Bin Abhulhak, Devona Chun-Furlong, Deborah Harrington, Emily Harlynn, Marjorie Schmitt, Constance Shelsky, Patricia Feldick, Mary Cherrico, Courtney Jagle, Nicholas Warnecke, Debra Myer, Deanna J. Ruder, Albina Underwood, Alan Rauba, George Carr, Barbara Oberhaus, Jessica Vanderfeltz, Mary Jo Stucky-Heil, Dale R. Gibson, Vonnie Fuentes, Kimberly L. Talbot, William C. Simon, Katlyn J. Grimes, Christina R. Wheeler, Cassaundra Shultz, Rhonda A. Metcalf, Jennifer L. Hill, Michelle R. Oliver, Basharat Ahmad, Fouzal Azeem, Abdul Rahim, George H. Freeman, Dawn Bloch, Heather Freeman, Jamie Brown, Sarah Rosbach, Pamela Melander, Nick Taralson, Alex Liu, Katlyn Harms, Mahfouz Michale, Jose Lopez, Maria Revoredo, Shari Edevane, Sarah Shawley, Timothy L. Jackson, Michael J. Oliver, Dina DeSalle, Patricia J. Matlock, Ionna M. Beraun, Heather Hendrix, Garrett Bromley, Ashley Niemerski, Gabby Teran, Sonia Guerrero, Murtaza Marvi, Zehra Palanpurwala, Andrea Torres, Patty Gloyd, Michelle Conger, Aziz Laurent, Olia Nayor, Catalina S. Villanueva, Munira Khambati, Tabetha J. Mumford, Melanie J. Castillo, Taddese Desta, Jerome Robinson, La Shawn Woods, Anita Bahri, Nancy Herrera, Cecilia Casaclang, Jeffrey R. Unger, Geraldine Martinez, Mia K. Moon, Stephen M. Mohaupt, Larry Sandoval, Louisito Valenzuela, Victora Ramirez, Nelly Mata, Veronica Avila, Marisol Patino, Cynthia Montano-Pereira, Omar Barnett, William M. Webster, Lorraine M. Christensen, Leighna Bofman, Melanie Livingston, Stacey Adams, Joseph Hobbs, Leesa Koskela, Mia Katz, Samuel Mujica-Trenche, Franklin Cala, Noreen T. Rana, Jennifer Scarlett, Milagros Cala Anaya, Marsha R. Jones, Kelly D. Hollis, Debbie Roth, Kristin Eads, Tina Watts, Judy Perkins, Alice Arnold, Daniel C. Ginsberg, Denise Quinn, Nicole Cureton, David B. Fittingoff, Mohammed I. Iqbal, Stephen R. White, Edith Sisneros, Michelle Ducca, David Streja, Danny Campos, Jennifer L. Boak, Farzeen Amir, Felice Anderson, James J. Kmetzo, Mary O. Bongarzone, Dawn Scott, Mary Grace De Leon, Cynthia Buda, William Graettinger, Michelle Alex, Erika Hess, James Govoni, Melissa Bartel, Travis L. Monchamp, Julie S. Roach, Sara Gibson, Amy M. Allfrey, Kristen Timpy, Kathy Bott, Karin A. Soucy, Jean Willis, Cecilia A. Valerio, Anusha Chunduri, Rebecca Coker, Nicole Vidrine, Ellen A. Thompson, Mark A. Studeny, Melissa K. Marcum, Tammy S. Monway, Douglas L. Kosmicki, Melissa J. Kelley, Corey M. Godfrey, Susan L. Krenk, Randy R. Holcomb, Deb K. Baehr, Mary K. Trauernicht, David Rowland Lowry, Betty Bondy Herts, Jeanne E Phelps, Jean-Marie Downing, Carol Gamer Dignon, Elisabeth S. Cockrill, Pravinchandra G. Chapla, Diane Fera, Margaret Chang, Patricia Fredette, Tamie Ashby, Renee Bergin, Zebediah A. Stearns, David B. Ware, Rachael M. Boudreaux, Joanna Rodriguez, Robert McKenzie, Amanda Huber, Rebecca Sommers, Heather Rowe, Stacy McLallen, Michale Haynes, Ashley Adamson, Janice Henderson, Lori McClure, Beverly A. Harris, Laura Ference, Sue Meissner-Dengler, Lisa Treasure, Doreen Nicely, Timothy L. Light, Tracey A. Osborn, Kimberly J. Mai, Pablo Vivas, Jose Rios, Dunia Rodriguez, Roger DeRaad, James Walder, Oscar Bailon, Denice Hockett, Debbie Anderson, Kelli McIntosh, Amber Odegard, Andrew Shepherd, Mary Seifert, Laurence Kelley, Rajendra Shetty, Michael Castine, David Brill, Gregory Fisher, Nicole Richmond, Kathleen Gray, Patricia Miller, Charlene Coneys, Yarixa Chanza, Monica Sumoza, Victoria M. Caudill, Kelly D. Harris, Courtney A. Manion, Melody J. Lineberger-Moore, Julie J. Wolfe, Barbara J. Rosen, Patricia DiVito, Janet L. Moffat, Christina Michaelis, Prashant Koshy, Diana Perea, Ghaith Al Yacoub, Stephanie Sadeghi, Thomas D. LeGalley, Rudolph F. Evonich, William J. Jean, Gary M. Friesen, John M. Pap, David A. Pesola, Mark D. Cowan, Kristofer M. Dosh, Dianna Larson, Adele M. Price, Jodi A. Nease, Jane E. Anderson, Lori A. Piggott, Robert Iwaoka, Kevin Sharkey, Edward McMillan, Laurie Lowder, Latisha Morgan, Kyle Davis, Tara Caldwell, Erica Breglio, Jasmine Summers, Rachel Poulimas, Muhammad Zahid, Hamid Syed, Maria Escobar, Jacob Levy, Rahma Warsi, Carol Ma, Puxiao Cen, Kimberly A. Cawthon, Delores B. Barnes, Deanna G. Allen, Margaret L. Warrington, Carol R. Stastny, Robin J. Michaels, Mohamad Saleh, John Sorin, Sunny Rathod, Urakay Juett, Steven Spencer, Aziza Keval, Jill McBride, Shane Young, Catherine Baxter, Carol Rasmussen, Shari L. Coxe, Luis Campos, Shahin Tavackoli, Diana Beckham, Darlynee Sanchez, Karanjit Basrai, Dorian Helms, Erica Clinton, Kasie Smith, Henry Cusnir, Mary Klaus Clark, Madhavagopal V. Cherukuri, Ameta Scarfaru, Stephen D. Nash, Loretta C. Grimm, Anna Grace, Kylie McElheran, Dino Subasic, Zedrick Buhay, Janet Litvinoff, Deepak Shah, Shannon Cervantes, Freda Usher, Farra Yasser, Theodore Trusevich, Ronnie L. Garcia, Jamison Wyatt, Rahul Bose, Holllilyn Miska, Traci Spivey, Amy B. Wren, Katie E. Vance, Lani L. Holman, Pam Gibbons, Elaine Eby, Sandra Shepard, Soratree Charoenthongtrakul, Brett Snodgrass, Mohammed Nazem, Shelly Keteenburg, Prathima Murthy, Frederic Prater, Ashley Rumfelt, Christina Eizensmits, Lisa Iannuzzi, Pourus R. Patel, Clellia Bergamino, Elizabeth McFeaters, Botros Rizk, Emiljia Pflaum, Danny Kalish, Rex Ambatali, Mona Ameli, Delaina Sanguinetti, Rakesh Vaidya, Martinus A.W. Broeders, Dorman Henrikus, Adrianus F.M. Kuijper, Nadea Al-Windy, Michael Magro, Karim Hamraoui, Ismail Aksoy, Guy L.J. Vermeiren, H.W.O. Roeters van Lennep, Gerard Hoedemaker, Johannes Jacobus Remmen, Kjell Bogaard, Dirk van der Heijden, Nicole MJ Knufman, Joost Frederiks, Johannes Willem Louwerenburg, Piet van Rossum, Johannes Milhous, Peter van der Meer, Arno van der Weerdt, Rob Breedveld, Mitran Keijzers, Walter Hermans, Ruud van de Wal, Peter A.G. Zwart, Marc M.J.M. van der Linden, Gerardus Zwiers, Dirk J. Boswijk, Jan Geert Tans, Jacob van Eck, Maarten V. Hessen, Barnabas J.B. Hamer, Stieneke Zoet-Nugteren, Lucien Theunissen, E.A. van Beek, Remco Nijmeijer, Pieter R. Nierop, Gerard Linssen, H.P. Swart, Timo Lenderink, Gerard L. Bartels, Frank den Hartog, Brian J. Berg van den, Wouter van Kempen, Susanne Kentgens, Gloria M. Rojas Lingan, Martinus M. Peeters, Hilligje Keterberg, Melchior Nierman, Annemieke K. den Hollander, Jacqueline Hoogendijk, Christine Voors-Pette, Vicdan Kose, Peter Viergever, Larysa Yena, Viktor Syvolap, Mykola P. Kopytsya, Olga Barna, Svitlana S. Panina, Mykhailo I. Lutai, Oxana V. Shershnyova, Iryna Luzkiv, Larysa S. Bula, Sergii Zotov, Ivan Vyjhovaniuk, Olena Lysunets, Volodymyr I. Koshlia, Nataliya Sydor, Myroslava F. Vayda, Olexiy Ushakov, Mykola Rishko, Viktor P. Shcherbak, Yevgeniya Svyshchenko, Vira Tseluyko, Andriy Yagensky, Viktoriia I. Zolotaikina, Olga Godlevska, Larysa Ivanova, Olena Koval, Olena I. Mitchenko, Galyna Y. Kardash, Yurii S. Rudyk, Mykola Stanislavchuk, Volodymyr Ivanovych Volkov, Olena G. Karlinskaya, Susanna A. Tykhonova, Nikolay Vatutin, Ganna Smirnova, Volodymyr M. Kovalenko, Viktor Lizogub, Denys Sebov, Oleksandr Dyadyk, Svetlana Andrievskaya, Mykola P. Krasko, Alexander N. Parkhomenko, Lidiya Horbach, Iryna G. Kupnovytska, Tetyana Pertseva, Oleksandr Karpenko, Dmytro Reshotko, Svitlana V. Zhurba, Leonid Rudenko, Viktoriia Yu Zharinova, Valerii B. Shatylo, Yuriy I. Karpenko, Mariya A. Orynchak, Tatiana R. Kameneva, Elena Zherlitsina, Diana N. Alpenidze, Grigoriy P. Arutyunov, Elena Baranova, Boris Bart, Dmitriy I. Belenkiy, Svetlana A. Boldueva, Elena A. Demchenko, Vera V. Eltishcheva, Alexander M. Gofman, Boris M. Goloshchekin, Ivan Gennadyevich Gordeev, Nikolay Gratsianskiy, Gadel Kamalov, Niyaz R. Khasanov, Irina M. Kholina, Zhanna D. Kobalava, Elena V. Kobeleva, Alexandra O. Konradi, Victor A. Kostenko, Andrey Dmitrievich Kuimov, Polina Y. Ermakova, Sofia K. Malyutina, Alexey V. Panov, Natalia V. Polezhaeva, Olga Reshetko, Nataliya P. Shilkina, Sergey B. Shustov, Elena A. Smolyarchuk, Raisa I. Stryuk, Elena Yurievnar Solovieva, Andrey V. Susekov, Natalia Vezikova, Svetlana N. Ivanova, Alexander A. Petrov, Vladimir O. Konstantinov, Alina S. Agafina, Victor Gurevich, Konstantin N. Zrazhevskiy, Tatiana V. Supryadkina, Nikita B. Perepech, Vadim L. Arkhipovskiy, Dmitry Yu Butko, Irina A. Zobenko, Olga V. Orlikova, Viktor Mordovin, Olga L. Barbarash, Anastasiya Lebedeva, Vladimir Nosov, Oleg V. Averkov, Elena P. Pavlikova, Yuri B. Karpov, Marina Lvovna Giorgadze, Oleg A. Khrustalev, Mikhail Arkhipov, Tatiana A. Raskina, Julia V. Shilko, Yulia Samoilova, Elena D. Kosmacheva, Sergey V. Nedogoda, Kathleen Coetzee, Lesley J. Burgess, F.C.R. Theron, Iftikhar O. Ebrahim, Gerbrand A. Haasbroek, Maria Pretorius, Julien S. Trokis, Dorothea V. Urbach, Mark J. Abelson, Adrian R. Horak, Aysha E. Badat, Ellen M. Makotoko, Hendrik Du Toit Theron, Padaruth Ramlachan, Clive H. Corbett, Ismail H. Mitha, Hendrik F.M. Nortje, Dirkie J. Jansen van Rensburg, Peter J. Sebastian, F.C.J. Bester, Louis J. van Zyl, Brian L. Rayner, Elżbieta Błach, Magda Dąbrowska, Grzegorz Kania, Agata E. Kelm-Warchol, Leszek P. Kinasz, Janusz Korecki, Mariusz Kruk, Ewa Laskowska-Derlaga, Andrzej Madej, Krzysztof Saminski, Katarzyna Wasilewska, Katarzyna Szymkowiak, Małgorzata Wojciechowska, Natalia Piorowska, Andrzej Dyczek, Rajpal K. Abhaichand, Ramesh B. Byrapaneni, Basavanagowdappa Hattur, Malipeddi Bhaskara Rao, Nitin Ghaisas, Sujit Shankar Kadam, Jugal B. Gupta, Santhosh M. Jayadev, V.A. Kothiwale, Atul Mathur, Vijay Bhaskar, Ravi K. Aluri, Udaya P. Ponangi, Mukesh K. Sarna, Sunil Sathe, Manish K. Sharma, Jilendra Pal Singh Sawhney, Chakrabhavi B. Keshavamurthy, Arun Srinivas, Hemant P. Thacker, A. Sharda, Johny Joseph, Sunil Dwivedi, Viswanathan Mohan, Rajendra K. Premchand, Jacques Bedard, Jean Bergeron, Ronald Collette, David Crowley, Richard Dumas, Sam Henein, Geoff Moran, William F. O’Mahony, Michael O’Mahony, Sammy Chan, Mark H. Sherman, Graham C. Wong, Brian D. Carlson, Milan K. Gupta, David Borts, Sean R. Peterson, Martyn Chilvers, Allan J. Kelly, Jean C. Gregoire, Simon Kouz, Josep Rodés Cabau, Minodora Andor, Mircea Cinteza, Radu Ciudin, Radu I. Cojan, Roxana O. Darabont, Dan-Lucian Dumitrascu, Carmen Fierbinteanu-Braticievici, Ana Gabriela Fruntelata, Constantin Militaru, Bogdon E. Minescu, Doina Luminita Serban, Florin Mitu, Dorel Nastase Melicovici, Ovidiu Petrascu, Octavian M. Pirvu, Cristian Podoleanu, Calin Pop, Rodica-Valentina V. Stanescu-Cioranu, Adrian Tase, Cristina Voiculet, Constantine N. Aroney, Anthony M. Dart, Timothy Davis, Karam Kostner, David N. O’Neal, Peter W. Purnell, Bhuwanendu B. Singh, David R. Sullivan, Peter Thompson, Gerald F. Watts, Adam F. Blenkhorn, John V. Amerena, Rafeeq Samie, Randall Hendriks, Joseph Proietto, Nikolai Petrovsky, Alan Whelan, David Colquhoun, Russell S. Scott, Simon C. Young, Tammy Pegg, Samuel JS Wilson, Andrew W. Hamer, Richard A. Luke, Hamish H. Hart, Gerard P. Devlin, Gerard T. Wilkins, Ian F. Ternouth, Samraj Nandra, Bruno S. Loeprich, Nicole McGrath, Stuart L. Tie, Rob J. Bos, Alexandra Wils, Tamara Jacobs, Erik A. Badings, Lillian A. Ebels-Tuinbeek, Mayke L. Scholten, Esther Bayraktar-Verver, Debby Zweers, Manoek Schiks, Carolien Kalkman, Tineke Tiemes, Jeanette Mulderij, Katarzyna Dabrowska, Wilma Wijnakker, Riny Van de Loo, Jeanne de Graauw, Giny Reijnierse, Mirjam van der Zeijst, Mariska Scholten, Henk R. Hofmeijer, Antoinette van Dijk-van der Zanden, Dineke J. van Belle, Jan Van Es, Gera Van Buchem, Wendy Zijda, Harald Verheij, Linnea Oldenhof-Janssen, Martina Bader, Marije Löwik, Sandra Stuij, Pascal Vantrimpont, Krista van Aken, Karen Hamilton, Han Blömer, Gabriela van Laerhoven, Raymond Tukkie, Maarten Janssen, Gerard Verdel, Jon Funke Küpper, Bob van Vlies, Caroline Kalkman, Joke Vooges, Marinella Vermaas, Rachel Langenberg, Niek Haenen, Frans Smeets, Arko Scheepmaker, Marcel Grosfeld, Ilvy Van Lieshout, Marleen van den Berg, Marian Wittekoek, Petra Mol, Antionette Stapel, Margaretha Sierevogel, Nancy van der Ven, Annemiek Berkelmans, Eric Viergever, Hanneke Kramer, Wilma Engelen, Karen V. Houwelingen, Thierry X. Wildbergh, Arend Mosterd, Coriet Hobé-Rap, Marjan van Doorn, Petra Bunschoten, Michel Freericks, Mireille Emans, Petra Den Boer-Penning, Els Verlek, Christine Freericks, Cornelis de Nooijer, Christina Welten, Ingrid Groenenberg, Claudia van der Horst, Esther Vonk, Geert Tjeerdsma, Gerard M. Jochemsen, Corinne van Daalen, Ingrid Y. Danse, Lucy Kuipers, Anke Pieterse, Antonius Oomen, Daan de Waard, Willem Jan Flu, Zusan Kromhout, Petra Van der Bij, Rob Feld, Brigitta Hessels-Linnemeijer, Rob Lardinois, Jan L. Posma, Zwanette R. Aukema-Wouda, Marjolijn Hendriks-van Woerden, Desiree van Wijk, Driek P. Beelen, Ingrid H. Hendriks, Jan J. Jonker, Stefanie Schipperen, Vicdan Köse, Gloria Rojas, Linda Goedhart, Hanneke van Meurs, Jacqueline Rijssemus, Lindy Swinkels-Diepenmaat, Marloes de Louw-Jansen, Dominique Bierens-Peters, Willem W. van Kempen, Marianne E. Wittekoek, Irmaina Agous, Geert Schenk, Janneke Wittekoek, Kevin Cox, Deborah F. Julia, Jan J.C. Jonker, Roel Janssen, Melchor Nierman, Hilligje Katerberg, Irene van der Haar, Willem W. Van Kempen, Taco van Mesdag, Leyda M. Alvarez Costa, Manon Schensema, Salomé Zweekhorst, Deborah Font Julia, Lauri Hanewinckel, Joyce Olsthoorn, Johan C. Berends, Arie C. van der Spek, Roy van der Berg, Rob J. Timmermann, Ingrid Boerema, Iryna Mudruk, Anna Khrystoforova, Serhii Kyselov, Yaroslava V. Hilova, Pavlo Logoida, Nataliia A. Sanina, Ilona P. Golikova, Olena O. Nemchyna, Ivan I. Isaichikov, Olga B. Potapova, Iurii V. Gura, Larysa Berestetska, Olena O. Kulianda, Oleksandr Tantsura, Oleksandr S. Kulbachuk, Volodymyr Petsentiy, Ihor Biskub, Tetyana Handych, Oleg Lagkuti, Alyna Gagarina, Taras Chendey, Oksana F. Bilonko, Olena Matova, Larysa Bezrodna, Olena Yarynkina, Tetiana Ovdiienko, Volodymyr Randchenko, Maryna Mospan, Olena Butko, Olga Romanenko, Mykhailo Pavelko, Iryna Sichkaruk, Svitlana O. Lazareva, Olena A. Kudryk, Inessa M. Koltsun, Tetiana Magdalits, Sergei Zadorozhniy, Kira Kompaniiets, Andrii Ivanov, Sergiy Romanenko, Pavlo Kaplan, Vadym Y. Romanov, Oksana P. Mykytyuk, Nataliia S. Zaitseva, Sergiy N. Pyvovar, Lyudmyla Burdeuna, Emerita Serdobinska, Tatiana I. Shevchenko, Igor I. Ivanytskyi, Olena V. Khyzhnyak, Nataliya Kalinkina, Olena Keting, Olena Sklyanna, Olga Kashanska, Anna Shevelok, Marina Khristichenko, Ievgenii Y. Titov, Danilenko O. Oleksander, Nataliia S. Polenova, Nataliia Altunina, Viktoriia Kororaieva, Stanislav Zborovskiy, Leonid Kholopov, Iurii Suliman, Lanna Lukashenko, Stanislav Shvaykin, Olexandr M. Glavatskiy, Roman O. Sychov, Roman L. Kulynych, Oleksandr A. Skarzhevskyi, Nataliia V. Dovgan, Marta Horbach, Olga Cherkasova, Iryna Tyshchenko, Liudmyla Todoriuk, Svitlana Kizim, Nataliia Brodi, Oleksandr Ivanko, Olga Garbarchuk, Liudmyla Alieksieieva, Tetiana L. Shandra, Olena Beregova, Larisa An Bodretska, Svitlana S. Naskalova, Ivanna A. Antoniuk-Shcheglova, Olena V. Bondarenko, Natalia G. Andreeva, Iryna I. Vakalyuk, Olha S. Chovganyuk, Nataliya R. Artemenko, Kiril A. Maltsev, Natalia Kalishevich, Natalia G. Kondratyeva, Svetlana A. Nikitina, Maria V. Martjanova, Anna V. Sokolova, Dmitrii O. Dragunov, Olga Kolesnik, Vera Larina, Oxana V. Tsygankova, Maria Ivanova, Illia A. Karpov, Elena M. Aronova, Ekaterina S. Vedernikova, Ekaterina I. Lubinskaya, Taras Y. Burak, Sergey I. Skichko, Farhad Rasulev, Ekaterina B. Soldatova, Alexander L. Fenin, Ilya I. Laptev, Elena E. Luchinkina, Alexandr Akatov, Natalia V. Polenova, Natalia N. Slavina, Irina N. Korovnika, Marina Yu Prochorova, Regina Shakirova, Elena N. Andreicheva, Olga A. Krasnova, Tinatin V. Lobzhanidze, Tatiana B. Dmitrova, Viktoriya V. Stakhiv, Maria I. Pechatnikova, Alexandra V. Panova, Maria Y. Tipikina, Oxana P. Rotar, Nikolay A. Bokovin, Saule K. Karabalieva, Farid Y. Tumarov, Elena V. Vasileva, Natalya Gennadevna Lozhkina, Ekaterina V. Filippova, Alisa I. Sharkaeva, Ekanerina V. Filippova Deilik, Natalia Yu Tolkacheva, Elena N. Domracheva, Andrey N. Ryabikov, Inga T. Abesadze, Marianna Z. Alugishvili, Elena P. Nikolaeva, Nadezda V. Smirnova, Valentina I. Rodionova, Polina V. Dolovstaya, Igor E. Yunonin, Sergey V. Kadin, Tatyana S. Sveklina, Anna V. Bushmanova, Elena L. Barkova, Irina S. Gomova, Yana V. Brytkova, Tatiana B. Ivanova, Marina Y. Zubareva, Inga Skopets, Lybov A. Galashevskaya, Emilia D. Butinskaya, Olga G. Gusarova, Natalia B. Kalishevich, Yana R. Pavlova, Marianna P Serebrenitskaya, Vitalina F. Grygorieva, Gulnara R. Kuchaeva, Inna A. Vasileva, Gulnara I. Ospanova, Yulia V. Vahrusheva, Irina A. Semenova, Irina E.E. Mikhailova, Olga O. Kvasova, Valeria D. Shurygina, Alexey E. Rivin, Alexey O. Savelyev, Alexey A. Savelyev, Olesya O. Milyaeva, Nadezhda N. Lapshina, Ninel A. Lantsova, Pavel V. Alexandrov, Evgeniy A. Orlikov, Alla Falkovskaya, Tatiana Ripp, Sergei Triss, Stanislav Pekarskiy, Sitkova Ekaterina, Evgeniya N. Zhuravleva, Olga Perova, Galina Kovaleva, Liubov Koroleva, Lydia Mishchenko, Boris P. Garshin, Svetlana A. Kutuzova, Lyudmila I. Provotorova, Igor P. Zadvorny, Olga V. Okhapkina, Anatoly O. Khrustalev, Tatiana Suvorova, Elena S. Shaf, Varvara A. Vershinina, Andrey A. Kozulin, Oxana A. Oleynik, Irina Y. Martynova, Natalia V. Kizhvatova, Alla S. Salasyuk, Vera V. Tsoma, Alla A. Ledyaeva, Elena V. Chumachek, S.C. Blignaut, Tersia Y. Alexander, Chano Du Plessis, Thirumani Govender, Samatha M. Du Toit, Leya Motala, Areesh Gassiep, Christina Naude (Smit), Marli Terblanche, Marlien Snoer (Kruger), Berenice Pillay, De Vries Basson, Marisa E. Theron, Bianca Fouche, Mareli E. Coetzee, Pieter Odendall, Frederik H. Van Wijk, Anna-Mari Conradie, Trudie Van der Westhuizen, Carine Tredoux, Mohamed S. Mookdam, Andie J. Van der Merwe, Karin Snyman, Gerda Smal, Yvonne De Jager, Thomas A. Mabin, Annusca King, Lindy L. Henley, Brenda M. Zwane, Jane Robinson, Marinda Karsten, Andonia M. Page, Valerie Nsabiyumva, Charmaine Krahenbuhl, Jaiprakash D. Patel, Yunus E. Motala, Ayesha Dawood, Nondumiso B. Koza, Lenore M.S. Peters, Shavashni Ramlachan, Wilhelm J. Bodenstein, Pierre Roux, Lizelle Fouche, Cecilia M. Boshoff, Haroon M. Mitha, Fathima Khan, Henry P. Cyster, Helen Cyster, E. C. Wessels, Florence J. Jacobs, Melanie A. Sebastian, Deborah A. Sebastian, Nadia Mahomed, Ignatius P. Immink, Celia Cotzee, Tanja Cronje, Madele Roscher, Maria Le Roux, Yvonne A. Trinder, Renata Wnętrzak-Michalska, Magdalena Piszczek, Andrzej Piela, Ewa Czernecka, Dorota Knychas, Alina Walczak, Izabella Gładysz, Katarzyna Filas, Ewelina Kiluk, Krzysztof Świgło, Iwona Jędrzejczyk, Kamila Łuczyńska, Katarzyna Tymendorf, Wojciech Piesiewicz, Wojciech L. Kinasz, Stefan Samborski, Ilona Bartuś, Gramzyna Latocha Korecka, Ewa Gulaj, Jolanta Sopa, Bogusław Derlaga, Marcin Baisiak, Allicia Kowalisko, Edyta Stainszewska-Marasazlek, Bartosz Szafran, Malgorzata Swiatkiewicz, Artur Racewicz, Sławomir Grycel, Jerzy Supronik, Sylwia Walendziuk, Magdalena Tarantowicz, Agata Stasiak, Anna Sidorowicz-Białynicka, Marek Dwojak, Ewa Jaźwińska-Tarnawska, Katarzyna Kupczyk, Kamila Martowska, Kamila Kulon, Katarzyna Gajda, Bivin Wilson, Krithika Velusamy, Swaidha S. Sadhiq, Bhavani Siddeshi, M. Bhanukumar, Abhishek Srivatsav, Madhan Ramesh, Sri Harsha Chalasani, Mini Johnson, Prashanth Gopu, Jeesa George, Sowmya Reddy, Swetha Tessy Thara Eleena, Damodara Rao Kodem, Haritha N. Nakkella, Padma Kumari Mandula, Anjan Kumar Vuriya, Syamala Rajana, Aruna Kale, Tiwari Rajeev, Raina Jain, Vipin Jain, Srilakshmi Mandayam Adhyapak, Lumin Sheeba, Uma C R, Ramya R, Aditya V. Kulkarni, M.S. Ganachari, Ruma Sambrekar, Mohammad Bilal, Kalyan Chakravarthy, Ravi Badhavath, Sravan Kumar, Meenakshi Simhadri, Farooque Salamuddin, Venkat Prasad, Vivek Dwivedi, Sudha Sarna, Tilak Arora, Deepak Chawla, Archana Sathe, Chaware Gayatree, Ajeet Nanda, Ram Avtar, Jyoti Sharma, Vaibhavi P S, Sasirekha D, Deepthi Kobbajji, Ramya Ningappa, Shwetha Shree, Chandrashekar K, Nandini M R, Sowjanya S, Devika I G, Yashaswini N, Sonika G, Rathna L, Priyanka R, Rupal J. Shrimanker, Lakshmi Vinutha Reddy, K. Sumathi, Babitha Devi, Bina N. Naik, Rohini Manjunath, Rajeshwari Ashok, Tony V. Kunjumon, Jesline Thomas, Shaik Samdhani, Kasthuri Selvam, Poongothai Subramani, Nandakumar Parthasarathy, Nirmal K. Bohra, Anvesh K. Gatla, Cheryl Horbatuk, Julie Sills, E B. Davey, Liz Paramonczyk, Olga Racanelli, Sandy Strybosch, Andre Belanger, Jean Palardy, Alicia Schiffrin, Sylvie Gauthier, Norman Kalyniuk, Shawn D. Whatley, Heather Lappala, Grishma Patel, Matthew Reeve, Catherine Moran, Jody Everitt, Teresa Ferrari, Christine Bouffard, Jirir Frohlich, Gordon Francis, John Mancini, Gregory Bondy, Debbie DeAngelis, Patricia Fulton, David W. Blank, Angela Lombardo, Mylène Roy, Jackie Chow, Hyman Fox, William J. Grootendorst, Angela Hutchinson, Sharon M. Chan, Christie Fitzgerald, Lynn Wilkins, Rebecca L. Raymond, Arlene Reyes, Lavoie Marc André, Denis Fortin, Hélène Ouimet, Thanh-Thao Tôn-Nu, Martine Dussureault, Marie-Hélène Blain, Madeleine Roy, Nathalie Kopajko, Chantal Fleury, Karine Maheux, Gabriela Valentina Ciobotaru, Maria C. Constantinescu, Carmen-Lucia Gherghinescu, Ana-Maria Avram, Ioan Manitiu, Aura Sinpetrean, Lucian Pop, Delia Lupu, Radu Usvat, Ana Petrisor, Nicoleta Dumitru, Camelia Moruju, Adelina Gheorghita, Magda V. Mitu, Cosmin Macarie, Ana Maria Pop, Maria-Catalina Diaconu, Iulia Grancea, Mihaela Cosma, Mihaela Crisan, Elizabeth Herron, Paul Nestel, Sally B. Kay, Kaye S. Carter, Imran Badshah, Ashley Makepeace, Jocelyn Drinkwater, Michelle England, Azette Rafei, Kylie Patterson, Alicia Jenkins, Sybil McAuley, Sue M. Kent, Joy E. Vibert, Leonie Perrett, Thomas David, Samantha L. Kaye, Monika O’Connor, Nimalie J. Perera, Nicole T. Lai, Kerry A. Kearins, Christinia Dicamillo, Heather Anderson, Louise Ferguson, Sharon D. Radtke, Charles T. Thamarappillil, Janice M. Boys, Anita K. Long, Toni Shanahan, Michael Nyguyen, Nicole Forrest, Gill Tulloch, Della Greenwell, Sarah L. Price, Aye N. Tint, Priya K. Sumithran, Tamara L. Debreceni, Lisa Walker, Mary Caruana, Kira Edwards, Maria Stathopoulos, Cilla Haywood, Dimitar Sajkov, Sharen Pringle, Anne Tabner, Kathrina Bartolay, Chamindi Abeyratne, Kylie Bragg, Patrick Mulhern, Peter Purnell, Lyn Williams, Jane Hamlyn, Aurelia Connelly, Jan Hoffman, Samantha Bailey, Jane Kerr, Zarnia Morrison, Sarah Maeder, Roberta McEwan, Prasanna Kunasekera, Patrice McGregor, Jo Young, Sharon Berry, Rick Cutfield, Michelle Choe, Catherine McNamara, Narrinder K. Shergill, Petra Crone, Miles G. Williams, Keith Dyson, Diana H. Schmid, Audrey C. Doak, Melissa Spooner, Colin Edwards, Anne Turner, Grainne M. McAnnalley, Raewyn A. Fisher, Fraser B. Hamilton, Denis H. Friedlander, Melissa R. Kirk, Jayne E. Scales, Marguerite A. McLelland, Neelam A. Dalman, Cathy E. Vickers, Carolyn Jackson, Wendy Coleman, Phillip I. Garden, and Wendy F. Arnold

Subjects
Male, medicine.medical_specialty, Rate ratio, Double-Blind Method, Ischemia, Risk Factors, Physiology (medical), Internal medicine, medicine, Clinical endpoint, Humans, Myocardial infarction, Coronary Artery Bypass, Stroke, Aged, business.industry, Unstable angina, Hazard ratio, Absolute risk reduction, Middle Aged, medicine.disease, Eicosapentaenoic Acid, Number needed to treat, Cardiology, Female, Cardiology and Cardiovascular Medicine, business
Abstract

Background: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery. Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting. Results: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92]; P =0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56–0.87]; P =0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50–0.81]; P =0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%–10.2%) in first events, with a number needed to treat of 16 (95% CI, 10–44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P =0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups. Conclusions: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.

Published
2021

3. Nuss Procedure for Pectus Excavatum: A Comparison of Complications Between Young and Adult Patients

Author

Lori M. van Roozendaal, Jean H.T. Daemen, Erik R. de Loos, Yvonne L. J. Vissers, Karel W.E. Hulsewé, Timo Lenderink, Alexander J. Pennings, Marieke van Horck, Matthijs H. van Gool, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, and CTC

Subjects
Pulmonary and Respiratory Medicine, Adult, medicine.medical_specialty, Adolescent, 030204 cardiovascular system & hematology, Nuss procedure, GUIDELINES, Risk Assessment, Cohort Studies, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Postoperative Complications, Pectus excavatum, Interquartile range, QUALITY-OF-LIFE, medicine, Humans, Orthopedic Procedures, Child, Retrospective Studies, REPAIR, OUTCOMES, business.industry, Incidence (epidemiology), Age Factors, Retrospective cohort study, Perioperative, Middle Aged, medicine.disease, Surgery, 030228 respiratory system, RAVITCH, Funnel Chest, Haller index, Cardiology and Cardiovascular Medicine, business, Complication
Abstract

Background. The Nuss procedure is the gold standard surgical treatment for pectus excavatum in young patients. Its use in adults has also been described, although it may be associated with increased postoperative morbidity resulting from higher chest wall rigidity. This study aimed to examine the risk of complications after the Nuss procedure in adult patients compared with young patients with pectus excavatum.Methods. This single-center retrospective cohort study evaluated all patients who underwent the Nuss procedure between 2006 and 2018. Patients were stratified by age as young (24 years old). The primary end point was the occurrence of perioperative or postoperative complications, subdivided into major (Clavien-Dindo class Ill a or higher) and minor (less severe than Clavien-Dindo class III). Between-group differences were analyzed using the Mann-Whitney U and the chi(2) test with post hoc analysis.Results. A total of 327 participants were included, 272 in the young group (median age, 16 years; interquartile range [IQR], 15 to 18 years; range, 11 to 24 years) and 55 in the adult group (median age, 32 years; IQR, 27 to 38 years; range, 25 to 47 years). The median Haller index was similar between groups (young, 3.7; IQR, 3.2 to 4.4 vs adult,3.6; IQR, 3.0 to 4.3; P = .44). The median follow-up was 34 and 36 months, respectively. The incidence of major complications was comparable between young and adult participants (P = .43). Minor complications occurred more often among adults (young, 4% vs adult, 11%; P = .002). Chronic postoperative pain was the only minor complication with a significant difference in incidence (young, 1% vs adult, 7%; P = .008).Conclusions. The Nuss procedure is a safe surgical treatment for pectus excavatum in both young and adult patients. The risk of major complications is comparable. However, adults more often have chronic pain. (C) 2021 by The Society of Thoracic Surgeons

Published
2021

4. Temporal Evolution of Serum Concentrations of High-Sensitivity Cardiac Troponin During 1 Year After Acute Coronary Syndrome Admission

Author

Victor J. van den Berg, Rohit M. Oemrawsingh, Victor A. W. M. Umans, Isabella Kardys, Folkert W. Asselbergs, Pim van der Harst, Imo E. Hoefer, Bas Kietselaer, Timo Lenderink, Anton J. Oude Ophuis, Ron H. van Schaik, Robbert J. de Winter, K. Martijn Akkerhuis, Eric Boersma, Maarten Mulder, Carl Schotborgh, Eelko Ronner, Anho Liem, David Haitsma, Arthur Maas, Ben Ilmer, Rene Dijkgraaf, S. Hong Kie, Alexander J Wardeh, Walther Hermans, Etienne Cramer, Pieter A Doevendans, Maarten L Simoons, Cardiovascular Centre (CVC), Cardiology, Clinical Chemistry, ACS - Heart failure & arrhythmias, and ACS - Atherosclerosis & ischemic syndromes

Subjects
Male, Epidemiology, Aftercare, 030204 cardiovascular system & hematology, GUIDELINES, 0302 clinical medicine, CLINICAL CHARACTERISTICS, Biological variation, Coronary Heart Disease, longitudinal studies, 030212 general & internal medicine, Myocardial infarction, Original Research, Netherlands, OUTCOMES, biology, troponin, Serum concentration, Middle Aged, Hospitalization, VARIABILITY, myocardial infarction, Cardiology, cardiovascular system, Female, Cardiology and Cardiovascular Medicine, troponinm, Acute coronary syndrome, medicine.medical_specialty, Cardiac troponin, Coronavirus disease 2019 (COVID-19), precision medicine, macromolecular substances, 03 medical and health sciences, Time frame, Troponin T, Internal medicine, medicine, Humans, Acute Coronary Syndrome, ELEVATION, biological variation, UNSTABLE ANGINA, business.industry, MORTALITY, Troponin I, Chronic Ischemic Heart Disease, medicine.disease, Troponin, Kinetics, Biological Variation, Population, biology.protein, business, Biomarkers
Abstract

Background Detailed insights in temporal evolution of high‐sensitivity cardiac troponin following acute coronary syndrome (ACS) are currently missing. We aimed to describe and compare the post‐ACS kinetics of high‐sensitivity cardiac troponin I (hs‐cTnI) and high‐sensitivity cardiac troponin T (hs‐cTnT), and to determine their intra‐ and interindividual variation in clinically stable patients. Methods and Results We determined hs‐cTnI (Abbott) and hs‐cTnT (Roche) in 1507 repeated blood samples, derived from 191 patients with ACS (median, 8/patient) who remained free from adverse cardiac events during 1‐year follow‐up. Post‐ACS kinetics were studied by linear mixed‐effect models. Using the samples collected in the 6‐ to 12‐month post‐ACS time frame, patients were then considered to have chronic coronary syndrome. We determined (differences between) the average hs‐cTnI and average hs‐cTnT concentration, and the intra‐ and interindividual variation for both biomarkers. Compared with hs‐cTnT, hs‐cTnI peaked higher (median 3506 ng/L versus 494 ng/L; P P r spearman =0.60), whereas the average hs‐cTnT concentration was 5 times more likely to be above the upper reference limit than hs‐cTnI. The intraindividual variations of hs‐cTnI and hs‐cTnT were 14.0% and 18.1%, while the interindividual variations were 94.1% and 75.9%. Conclusions Hs‐cTnI peaked higher after ACS and was quicker below the upper reference limit. In the post–6‐month samples, hs‐cTnI and hs‐cTnT were clearly not interchangeable, and average hs‐cTnT concentrations were much more often above the upper reference limit than hs‐cTnI. For both markers, the within‐patient variation fell largely below beween‐patient variation. Registration URL: https://www.trialregister.nl ; unique identifiers: NTR1698 and NTR1106.

Published
2021

5. Stabilization patterns and variability of hs-CRP, NT-proBNP and ST2 during 1 year after acute coronary syndrome admission

Author

Anton J. Oude Ophuis, Victor J. van den Berg, Imo E. Hoefer, Victor A. Umans, Pim van der Harst, Harry J.G.M. Crijns, Milos Brankovic, Bas L.J.H. Kietselaer, R.M. Oemrawsingh, K. Martijn Akkerhuis, Folkert W. Asselbergs, Ron H.N. van Schaik, Isabella Kardys, Timo Lenderink, Eric Boersma, Cardiovascular Centre (CVC), Cardiology, MUMC+: MA Cardiologie (9), RS: Carim - H01 Clinical atrial fibrillation, and Cardiologie

Subjects
Male, 0301 basic medicine, Clinical Biochemistry, Coronary Artery Disease, 030204 cardiovascular system & hematology, Coronary artery disease, 0302 clinical medicine, Risk Factors, Natriuretic Peptide, Brain, ARTERY-DISEASE, Longitudinal Studies, Prospective Studies, Myocardial infarction, biology, General Medicine, Middle Aged, Brain natriuretic peptide, C-REACTIVE PROTEIN, CHRONIC HEART-FAILURE, PROGNOSTIC VALUE, myocardial infarction, TERMINAL PROBNP, Cardiology, Biomarker (medicine), Female, medicine.symptom, Adult, Acute coronary syndrome, medicine.medical_specialty, N-terminal prohormone of brain natriuretic peptide (NTproBNP), ACUTE MYOCARDIAL-INFARCTION, Risk Assessment, Asymptomatic, 03 medical and health sciences, acute coronary syndrome (ACS), Internal medicine, medicine, Humans, Acute Coronary Syndrome, C-reactive protein (CRP), SOLUBLE ST2, Aged, business.industry, variability, NATRIURETIC PEPTIDE, MORTALITY, Biochemistry (medical), C-reactive protein, medicine.disease, ST2, Interleukin-1 Receptor-Like 1 Protein, Peptide Fragments, 030104 developmental biology, BIOLOGICAL VARIATION, biology.protein, business, Biomarkers, Blood sampling
Abstract

Objectives Details of the biological variability of high-sensitivity C-reactive protein (hs-CRP), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and ST2 are currently lacking in patients with acute coronary syndrome (ACS) but are crucial knowledge when aiming to use these biomarkers for personalized risk prediction. In the current study, we report post-ACS kinetics and the variability of the hs-CRP, NT-proBNP and ST2. Methods BIOMArCS is a prospective, observational study with high frequency blood sampling during 1 year post-ACS. Using 1507 blood samples from 191 patients that remained free from adverse cardiac events, we investigated post-ACS kinetics of hs-CRP, NT-proBNP and ST2. Biological variability was studied using the samples collected between 6 and 12 months after the index ACS, when patients were considered to have stable coronary artery disease. Results On average, hs-CRP rose peaked at day 2 and rose well above the reference value. ST2 peaked immediately after the ACS but never rose above the reference value. NT-proBNP level rose on average during the first 2 days post-ACS and slowly declined afterwards. The within-subject variation and relative change value (RCV) of ST2 were relatively small (13.8%, RCV 39.7%), while hs-CRP (41.9%, lognormal RCV 206.1/-67.3%) and NT-proBNP (39.0%, lognormal RCV 185.2/-64.9%) showed a considerable variation. Conclusions Variability of hs-CRP and NT-proBNP within asymptomatic and clinically stable post-ACS patients is considerable. In contrast, within-patient variability of ST2 is low. Given the low within-subject variation, ST2 might be the most useful biomarker for personalizing risk prediction in stable post-ACS patients.

Published
2020

6. Mobile health adherence for the detection of recurrent recent-onset atrial fibrillation

Author

Rachel M J van der Velden, Nikki A H A Pluymaekers, Elton A M P Dudink, Justin G L M Luermans, Joan G Meeder, Wilfred F Heesen, Timo Lenderink, Jos W M G Widdershoven, Jeroen J J Bucx, Michiel Rienstra, Otto Kamp, Jurren M van Opstal, Charles J H J Kirchhof, Vincent F van Dijk, Henk P Swart, Marco Alings, Isabelle C Van Gelder, Harry J G M Crijns, Dominik Linz, Cardiologie, RS: Carim - H01 Clinical atrial fibrillation, MUMC+: MA Med Staf Artsass Cardiologie (9), MUMC+: MA Med Staf Spec Cardiologie (9), RS: Carim - H08 Experimental atrial fibrillation, Cardiology, ACS - Heart failure & arrhythmias, and Cardiovascular Centre (CVC)

Subjects
Male, CARDIOVERSION, Heart Rate, Recurrence, Atrial Fibrillation, Electric Countershock, Humans, Female, RHYTHM, Cardiology and Cardiovascular Medicine, Anti-Arrhythmia Agents, Telemedicine, Aged
Abstract

ObjectiveThe Rate Control versus Electrical Cardioversion Trial 7–Acute Cardioversion versus Wait and See trial compared early to delayed cardioversion for patients with recent-onset symptomatic atrial fibrillation (AF). This study aims to evaluate the adherence to a 4-week mobile health (mHealth) prescription to detect AF recurrences after an emergency department visit.MethodsAfter the emergency department visit, the 437 included patients, irrespective of randomisation arm (early or delayed cardioversion), were asked to record heart rate and rhythm for 1 min three times daily and in case of symptoms by an electrocardiography-based handheld device for 4 weeks (if available). Adherence was appraised as number of performed measurements per number of recordings asked from the patient and was evaluated for longitudinal adherence consistency. All patients who used the handheld device were included in this subanalysis.Results335 patients (58% males; median age 67 (IQR 11) years) were included. The median overall adherence of all patients was 83.3% (IQR 29.9%). The median number of monitoring days was 27 out of 27 (IQR 5), whereas the median number of full monitoring days was 16 out of 27 (IQR 14). Higher age and a previous paroxysm of AF were identified as multivariable adjusted factors associated with adherence.ConclusionsIn this randomised trial, a 4-week mHealth prescription to monitor for AF recurrences after an emergency department visit for recent-onset AF was feasible with 85.7% of patients consistently using the device with at least one measurement per day. Older patients were more adherent.Trial registration numberNCT02248753.

Published
2022

7. Colchicine in patients with chronic coronary disease

Author

Stefan M, Nidorf, Aernoud T L, Fiolet, Arend, Mosterd, John W, Eikelboom, Astrid, Schut, Tjerk S J, Opstal, Salem H K, The, Xiao-Fang, Xu, Mark A, Ireland, Timo, Lenderink, Donald, Latchem, Pieter, Hoogslag, Anastazia, Jerzewski, Peter, Nierop, Alan, Whelan, Randall, Hendriks, Henk, Swart, Jeroen, Schaap, Aaf F M, Kuijper, Maarten W J, van Hessen, Pradyot, Saklani, Isabel, Tan, Angus G, Thompson, Allison, Morton, Chris, Judkins, Willem A, Bax, Maurits, Dirksen, Marco, Alings, Graeme J, Hankey, Charley A, Budgeon, Jan G P, Tijssen, Jan H, Cornel, Peter L, Thompson, Karen, Youl, Cardiology, and ACS - Heart failure & arrhythmias

Subjects
Male, medicine.medical_specialty, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Anti-Inflammatory Agents, Coronary Disease, 030204 cardiovascular system & hematology, law.invention, Coronary artery disease, 03 medical and health sciences, chemistry.chemical_compound, Geriatric cardiology, 0302 clinical medicine, All institutes and research themes of the Radboud University Medical Center, Randomized controlled trial, Double-Blind Method, law, Internal medicine, medicine, Colchicine, Humans, In patient, 030212 general & internal medicine, Aged, Proportional Hazards Models, Intention-to-treat analysis, Proportional hazards model, business.industry, Incidence (epidemiology), Incidence, General Medicine, Middle Aged, medicine.disease, Intention to Treat Analysis, chemistry, Cardiovascular Diseases, Chronic Disease, Cardiology, Female, business, Follow-Up Studies
Abstract

Evidence from a recent trial has shown that the antiinflammatory effects of colchicine reduce the risk of cardiovascular events in patients with recent myocardial infarction, but evidence of such a risk reduction in patients with chronic coronary disease is limited.In a randomized, controlled, double-blind trial, we assigned patients with chronic coronary disease to receive 0.5 mg of colchicine once daily or matching placebo. The primary end point was a composite of cardiovascular death, spontaneous (nonprocedural) myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization. The key secondary end point was a composite of cardiovascular death, spontaneous myocardial infarction, or ischemic stroke.A total of 5522 patients underwent randomization; 2762 were assigned to the colchicine group and 2760 to the placebo group. The median duration of follow-up was 28.6 months. A primary end-point event occurred in 187 patients (6.8%) in the colchicine group and in 264 patients (9.6%) in the placebo group (incidence, 2.5 vs. 3.6 events per 100 person-years; hazard ratio, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P0.001). A key secondary end-point event occurred in 115 patients (4.2%) in the colchicine group and in 157 patients (5.7%) in the placebo group (incidence, 1.5 vs. 2.1 events per 100 person-years; hazard ratio, 0.72; 95% CI, 0.57 to 0.92; P = 0.007). The incidence rates of spontaneous myocardial infarction or ischemia-driven coronary revascularization (composite end point), cardiovascular death or spontaneous myocardial infarction (composite end point), ischemia-driven coronary revascularization, and spontaneous myocardial infarction were also significantly lower with colchicine than with placebo. The incidence of death from noncardiovascular causes was higher in the colchicine group than in the placebo group (incidence, 0.7 vs. 0.5 events per 100 person-years; hazard ratio, 1.51; 95% CI, 0.99 to 2.31).In a randomized trial involving patients with chronic coronary disease, the risk of cardiovascular events was significantly lower among those who received 0.5 mg of colchicine once daily than among those who received placebo. (Funded by the National Health Medical Research Council of Australia and others; LoDoCo2 Australian New Zealand Clinical Trials Registry number, ACTRN12614000093684.).

Published
2020

8. High-frequency metabolite profiling and the incidence of recurrent cardiac events in patients with post-acute coronary syndrome

Author

Eric Boersma, Folkert W. Asselbergs, K. Martijn Akkerhuis, Victor J. van den Berg, Pim van der Harst, Rohit M. Oemrawsingh, Maxime M. Vroegindewey, Isabella Kardys, Bas L.J.H. Kietselaer, Timo Lenderink, RS: Carim - H01 Clinical atrial fibrillation, Cardiologie, Cardiovascular Centre (CVC), and Cardiology

Subjects
Male, Very low-density lipoprotein, Health, Toxicology and Mutagenesis, Metabolite, Clinical Biochemistry, Lipoproteins, VLDL, 030204 cardiovascular system & hematology, Biochemistry, Gastroenterology, vldl, chemistry.chemical_compound, 0302 clinical medicine, Recurrence, Prospective Studies, Prospective cohort study, Netherlands, RISK, Incidence, Incidence (epidemiology), CHOLESTEROL, Hazard ratio, lipoprotein, Middle Aged, 030220 oncology & carcinogenesis, Biomarker (medicine), Female, medicine.medical_specialty, Acute coronary syndrome, metabolite kinetics, Heart Diseases, lipids, 03 medical and health sciences, MAGNETIC-RESONANCE METABOLOMICS, Internal medicine, medicine, genomics, Humans, Metabolomics, Acute Coronary Syndrome, Particle Size, repeated measurements, Aged, business.industry, medicine.disease, Atherosclerosis, chemistry, Case-Control Studies, business, Biomarkers, Follow-Up Studies, Blood sampling
Abstract

Purpose: The aim of this study was to study temporal changes in metabolite profiles in patients with post-acute coronary syndrome (ACS), in particular prior to the development of recurrent ACS (reACS). Methods: BIOMArCS (BIOMarker study to identify the Acute risk of a Coronary Syndrome) is a prospective study including patients admitted for ACS, who underwent high-frequency blood sampling during 1-year follow-up. Within BIOMArCS, we performed a nested case-cohort analysis of 158 patients (28 cases of reACS). We determined 151 metabolites by nuclear magnetic resonance in seven (median) blood samples per patient. Temporal evolution of the metabolites and their relation with reACS was assessed by joint modelling. Results are reported as adjusted (for clinical factors) hazard ratios (aHRs). Results: Median age was 64 (25th–75th percentiles; 56–72) years and 78% were men. After multiple testing correction (p < 0.001), high concentrations of extremely large very low density lipoprotein (VLDL) particles (aHR 1.60/SD increase; 95%CI 1.25–2.08), very large VLDL particles (aHR 1.60/SD increase; 95%CI 1.25–2.08) and large VLDL particles (aHR 1.56/SD increase; 95%CI 1.22–2.05) were significantly associated with reACS. Moreover, these longitudinal particle concentrations showed a steady increase over time prior to reACS. Among the other metabolites, no significant associations were observed. Conclusion: Post-ACS patients with persistent high concentrations of extremely large, very large and large VLDL particles have increased risk of reACS within 1 year.

Published
2020

9. [Myocardial infarction with nonobstructive coronary arteries (MINOCA): indications for additional investigations and treatment]

Author

Tobias, Pustjens, Arnoud W J, van 't Hof, Timo, Lenderink, and Saman, Rasoul

Subjects
Male, Risk Factors, Myocardial Infarction, Humans, Female, Middle Aged, Coronary Angiography, Coronary Vessels, Magnetic Resonance Imaging, Aged
Abstract

Myocardial infarction with nonobstructive coronary arteries (MINOCA) has multiple potential underlying causes which can be subdivided into coronary, myocardial and non-cardiac disorders. On the basis of three case descriptions, we show that additional investigations are crucial in determining the underlying mechanism and starting suitable treatment. Depending on clinical presentation, risk factors and medical history, an LV angiogram, a provocation test with intracoronary acetylcholine and a cardiac MRI can contribute to finding the correct diagnosis. We further present a diagnostic algorithm to guide the clinician in the management of patients presenting with MINOCA.

Published
2020

10. Temporal evolution of myeloperoxidase and galectin 3 during 1 year after acute coronary syndrome admission

Author

Isabella Kardys, Victor J. van den Berg, Eelco Ronner, K. Martijn Akkerhuis, Elke Bouwens, Eric Boersma, Folkert W. Asselbergs, Timo Lenderink, Victor A. Umans, Maxime M. Vroegindewey, Pim van der Harst, Rohit M. Oemrawsingh, Cardiology, and Cardiovascular Centre (CVC)

Subjects
Male, medicine.medical_specialty, Acute coronary syndrome, Time Factors, Galectin 3, Galectins, 030204 cardiovascular system & hematology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Coronary plaque, Internal medicine, Medicine, Humans, 030212 general & internal medicine, Acute Coronary Syndrome, Aged, Netherlands, Peroxidase, biology, business.industry, Follow up studies, Blood Proteins, Middle Aged, medicine.disease, Hospitalization, Galectin-3, Myeloperoxidase, biology.protein, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Biomarkers, Cohort study, Follow-Up Studies
Abstract

Prior studies reported that Myeloperoxidase and Galectin-3, which are biomarkers of coronary plaque vulnerability, are elevated in acute coronary syndrome (ACS) patients. We studied the temporal evolution of these biomarkers early after ACS admission and prior to a recurrent ACS event during 1 year follow-up.

Published
2019

11. Early or delayed cardioversion in recent-onset atrial fibrillation

Author

Nikki A H A, Pluymaekers, Elton A M P, Dudink, Justin G L M, Luermans, Joan G, Meeder, Timo, Lenderink, Jos, Widdershoven, Jeroen J J, Bucx, Michiel, Rienstra, Otto, Kamp, Jurren M, Van Opstal, Marco, Alings, Anton, Oomen, Charles J, Kirchhof, Vincent F, Van Dijk, Hemanth, Ramanna, Anho, Liem, Lukas R, Dekker, Brigitte A B, Essers, Jan G P, Tijssen, Isabelle C, Van Gelder, Harry J G M, Crijns, L M, Rademakers, Medical and Clinical Psychology, Cardiology, ACS - Heart failure & arrhythmias, Promovendi CD, Cardiologie, RS: CARIM - R2 - Cardiac function and failure, RS: CARIM - R2.01 - Clinical atrial fibrillation, MUMC+: MA Med Staf Spec Cardiologie (9), MUMC+: KIO Kemta (9), RS: CAPHRI - R2 - Creating Value-Based Health Care, MUMC+: MA Cardiologie (9), RS: Carim - H01 Clinical atrial fibrillation, Cardiovascular Centre (CVC), ACS - Atherosclerosis & ischemic syndromes, ACS - Microcirculation, Cardiovascular Biomechanics, Center for Care & Cure Technology Eindhoven, Eindhoven MedTech Innovation Center, Signal Processing Systems, and Biomedical Diagnostics Lab

Subjects
Male, Digoxin, medicine.medical_treatment, Kaplan-Meier Estimate, DEVICE, 030204 cardiovascular system & hematology, Cardioversion, GUIDELINES, Digoxin/therapeutic use, 0302 clinical medicine, DESIGN, Calcium Channel Blockers/therapeutic use, Heart Rate, Recurrence, Atrial Fibrillation, ABLATION, Sinus rhythm, 030212 general & internal medicine, Stroke, Emergency Service, Atrial fibrillation, General Medicine, Middle Aged, Adrenergic beta-Antagonists/therapeutic use, Calcium Channel Blockers, Catheter, Treatment Outcome, Cardiology, Female, Electric Countershock/adverse effects, Emergency Service, Hospital, ECHOCARDIOGRAPHY, Anti-Arrhythmia Agents, STROKE, medicine.medical_specialty, Adrenergic beta-Antagonists, Electric Countershock, Anti-Arrhythmia Agents/adverse effects, Time-to-Treatment, SPONTANEOUS CONVERSION, 03 medical and health sciences, Hospital, ANTICOAGULATION, Internal medicine, Heart rate, medicine, MANAGEMENT, Humans, Recent onset, Aged, business.industry, Atrial Fibrillation/drug therapy, medicine.disease, TEMPORAL RELATIONSHIP, CATHETER, Quality of Life, business
Abstract

BACKGROUND: Patients with recent-onset atrial fibrillation commonly undergo immediate restoration of sinus rhythm by pharmacologic or electrical cardioversion. However, whether immediate restoration of sinus rhythm is necessary is not known, since atrial fibrillation often terminates spontaneously.METHODS: In a multicenter, randomized, open-label, noninferiority trial, we randomly assigned patients with hemodynamically stable, recent-onset (RESULTS: The presence of sinus rhythm at 4 weeks occurred in 193 of 212 patients (91%) in the delayed-cardioversion group and in 202 of 215 (94%) in the early-cardioversion group (between-group difference, -2.9 percentage points; 95% confidence interval [CI], -8.2 to 2.2; P = 0.005 for noninferiority). In the delayed-cardioversion group, conversion to sinus rhythm within 48 hours occurred spontaneously in 150 of 218 patients (69%) and after delayed cardioversion in 61 patients (28%). In the early-cardioversion group, conversion to sinus rhythm occurred spontaneously before the initiation of cardioversion in 36 of 219 patients (16%) and after cardioversion in 171 patients (78%). Among the patients who completed remote monitoring during 4 weeks of follow-up, a recurrence of atrial fibrillation occurred in 49 of 164 patients (30%) in the delayed-cardioversion group and in 50 of 171 (29%) in the early-cardioversion group. Within 4 weeks after randomization, cardiovascular complications occurred in 10 patients and 8 patients, respectively.CONCLUSIONS: In patients presenting to the emergency department with recent-onset, symptomatic atrial fibrillation, a wait-and-see approach was noninferior to early cardioversion in achieving a return to sinus rhythm at 4 weeks. (Funded by the Netherlands Organization for Health Research and Development and others; RACE 7 ACWAS ClinicalTrials.gov number, NCT02248753.).

Published
2019

12. Acute cardioversion vs a wait-and-see approach for recent-onset symptomatic atrial fibrillation in the emergency department: Rationale and design of the randomized ACWAS trial

Author

Bob Weijs, Brigitte A. B. Essers, Hemanth Ramanna, Elton A. M. P. Dudink, Marco Alings, Isabelle C. Van Gelder, Timo Lenderink, Jos Widdershoven, Joan G. Meeder, Justin G.L.M. Luermans, Bas L.J.H. Kietselaer, Vincent F. van Dijk, Jurren M. van Opstal, Lennert Kulker, A. H. Liem, Michiel Rienstra, Harry J.G.M. Crijns, Otto Kamp, Lukas R.C. Dekker, Wouter Holvoet, Martin H. Prins, RS: CARIM - R2.01 - Clinical atrial fibrillation, Cardiologie, RS: CAPHRI - R2 - Creating Value-Based Health Care, MUMC+: KIO Kemta (9), MUMC+: MA Med Staf Spec Cardiologie (9), RS: CARIM - R3.11 - Imaging, RS: CAPHRI - R5 - Optimising Patient Care, Epidemiologie, MUMC+: MA Cardiologie (9), Cardiology, ICaR - Heartfailure and pulmonary arterial hypertension, and Cardiovascular Centre (CVC)

Subjects
Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Electric Countershock, 030204 cardiovascular system & hematology, Cardioversion, law.invention, 03 medical and health sciences, Electrocardiography, 0302 clinical medicine, Quality of life, Randomized controlled trial, law, Heart Rate, RHYTHM CONTROL, Atrial Fibrillation, medicine, Clinical endpoint, Humans, FLUTTER, Sinus rhythm, 030212 general & internal medicine, Intensive care medicine, Infusions, Intravenous, Watchful Waiting, Flecainide, business.industry, Anticoagulants, Atrial fibrillation, Emergency department, medicine.disease, Female, Cardiology and Cardiovascular Medicine, business, Emergency Service, Hospital, Anti-Arrhythmia Agents, Watchful waiting, Metoprolol
Abstract

BACKGROUND: Current standard of care for patients with recent-onset atrial fibrillation (AF) in the emergency department aims at urgent restoration of sinus rhythm, although paroxysmal AF is a condition that resolves spontaneously within 24 hours in more than 70% of the cases. A wait-and-see approach with rate-control medication only and when needed cardioversion within 48 hours of onset of symptoms is hypothesized to be noninferior, safe, and cost-effective as compared with current standard of care and to lead to a higher quality of life.DESIGN: The ACWAS trial (NCT02248753) is an investigator-initiated, randomized, controlled, 2-arm noninferiority trial that compares a wait-and-see approach to the standard of care. Consenting adults with recent-onset symptomatic AF in the emergency department without urgent need for cardioversion are eligible for participation. A total of 437 patients will be randomized to either standard care (pharmacologic or electrical cardioversion) or the wait-and-see approach, consisting of symptom reduction through rate control medication until spontaneous conversion is achieved, with the possibility of cardioversion within 48 hours after onset of symptoms. Primary end point is the presence of sinus rhythm on 12-lead electrocardiogram at 4 weeks; main secondary outcomes are adverse events, total medical and societal costs, quality of life, and cost-effectiveness for 1 year.CONCLUSIONS: The ACWAS trial aims at providing evidence for the use of a wait-and-see approach for patients with recent-onset symptomatic AF in the emergency department.

Published
2017

13. Cohort profile of BIOMArCS: the BIOMarker study to identify the Acute risk of a Coronary Syndrome-a prospective multicentre biomarker study conducted in the Netherlands

Author

A. H. Liem, Timo Lenderink, Bas L.J.H. Kietselaer, Folkert W. Asselbergs, Anton J. Oude Ophuis, Maarten L. Simoons, Rene Dijkgraaf, Victor A. Umans, David Haitsma, Pieter A. Doevendans, Ben Ilmer, Robbert-Jan de Winter, K. Martijn Akkerhuis, Carl E. Schotborgh, Alexander J Wardeh, Walter R.M. Hermans, Eric Boersma, Arthur Maas, Ron H.N. van Schaik, Etienne Cramer, Pim van der Harst, Rohit M. Oemrawsingh, Eelko Ronner, Imo E. Hoefer, Cardiovascular Centre (CVC), Cardiology, Clinical Chemistry, RS: CARIM - R3.11 - Imaging, MUMC+: MA Med Staf Spec Cardiologie (9), Cardiologie, and RS: CARIM - R2.01 - Clinical atrial fibrillation

Subjects
Male, vulnerable period, Myocardial Infarction, risk stratification, Coronary Artery Disease, 030204 cardiovascular system & hematology, Cardiovascular Medicine, PLAQUE CHARACTERISTICS, Coronary artery disease, 0302 clinical medicine, Risk Factors, Clinical endpoint, ATHEROREMO-IVUS, ARTERY-DISEASE, TROPONIN-T, 030212 general & internal medicine, Myocardial infarction, Prospective Studies, Netherlands, Aged, 80 and over, Heart, General Medicine, Middle Aged, Prognosis, C-REACTIVE PROTEIN, CARDIOVASCULAR-DISEASE, Cohort, Cardiology, Disease Progression, Biomarker (medicine), Female, Risk assessment, Adult, medicine.medical_specialty, Acute coronary syndrome, HEART-DISEASE, Risk Assessment, 03 medical and health sciences, Internal medicine, medicine, Journal Article, Humans, Risk factor, Acute Coronary Syndrome, RADIOFREQUENCY INTRAVASCULAR ULTRASOUND, Aged, Cohort Profile, business.industry, Myocardium, medicine.disease, LUDWIGSHAFEN RISK, MYOCARDIAL-INFARCTION, Emergency medicine, business, Biomarkers
Abstract

PURPOSE: Progression of stable coronary artery disease (CAD) towards acute coronary syndrome (ACS) is a dynamic and heterogeneous process with many intertwined constituents, in which a plaque destabilising sequence could lead to ACS within short time frames. Current CAD risk assessment models, however, are not designed to identify increased vulnerability for the occurrence of coronary events within a precise, short time frame at the individual patient level. The BIOMarker study to identify the Acute risk of a Coronary Syndrome (BIOMArCS) was designed to evaluate whether repeated measurements of multiple biomarkers can predict such 'vulnerable periods'. PARTICIPANTS: BIOMArCS is a multicentre, prospective, observational study of 844 patients presenting with ACS, either with or without ST-elevation and at least one additional cardiovascular risk factor. METHODS AND ANALYSIS: We hypothesised that patterns of circulating biomarkers that reflect the various pathophysiological components of CAD, such as distorted lipid metabolism, vascular inflammation, endothelial dysfunction, increased thrombogenicity and ischaemia, diverge in the days to weeks before a coronary event. Divergent biomarker patterns, identified by serial biomarker measurements during 1-year follow-up might then indicate 'vulnerable periods' during which patients with CAD are at high short-term risk of developing an ACS. Venepuncture was performed every fortnight during the first half-year and monthly thereafter. As prespecified, patient enrolment was terminated after the primary end point of cardiovascular death or hospital admission for non-fatal ACS had occurred in 50 patients. A case-cohort design will explore differences in temporal patterns of circulating biomarkers prior to the repeat ACS. FUTURE PLANS AND DISSEMINATION: Follow-up and event adjudication have been completed. Prespecified biomarker analyses are currently being performed and dissemination through peer-reviewed publications and conference presentations is expected from the third quarter of 2016. Should identification of a 'vulnerable period' prove to be feasible, then future research could focus on event reduction through pharmacological or mechanical intervention during such periods of high risk for ACS. TRIAL REGISTRATION NUMBER: NTR1698 and NTR1106.

Published
2016

14. Multimarker risk model containing troponin-T, interleukin 10, myeloperoxidase and placental growth factor predicts long-term cardiovascular risk after non-ST-segment elevation acute coronary syndrome

Author

Stephan Fichtlscherer, Stephan Baldus, K.M. Akkerhuis, Christian W. Hamm, Eric Boersma, Timo Lenderink, M. L. Simoons, Christopher Heeschen, Rohit M. Oemrawsingh, and Cardiology

Subjects
Placental growth factor, Male, medicine.medical_specialty, Acute coronary syndrome, Population, Myocardial Infarction, Pregnancy Proteins, Electrocardiography, Troponin T, Internal medicine, medicine, Humans, Myocardial infarction, Risk factor, Acute Coronary Syndrome, education, Aged, Peroxidase, Placenta Growth Factor, Univariate analysis, education.field_of_study, business.industry, ST elevation, Middle Aged, medicine.disease, Prognosis, Interleukin-10, Europe, Endocrinology, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Epidemiologic Methods, Biomarkers
Abstract

Objective To evaluate the predictive value of seven biomarkers, which individually have been shown to be independent predictors, for use in a combined multimarker model for long-term cardiovascular outcome after non-ST-segment elevation acute coronary syndrome (NSTEACS). Design and Setting Levels of high-sensitivity C-reactive protein (hsCRP), myeloperoxidase, pregnancy-associated plasma protein A, placental growth factor (PlGF), soluble CD40 ligand (sCD40L), interleukin 10 (IL-10) and troponin-T (TnT) were determined in patients enrolled in the CAPTURE trial. Cox proportional hazard regression analyses were applied to evaluate the relation between biomarkers and the occurrence of all-cause mortality or non-fatal myocardial infarction (MI). Patients 1090 patients with NSTEACS. Main outcome measure All-cause mortality and non-fatal MI during a median follow-up of 4 years. Results The composite endpoint was reached by 15.3% of patients. Admission levels of TnT >0.01 mg/l (adjusted HR 1.8), IL-10 350 mg/l (1.5) and PlGF >27 ng/l (1.9) remained significant predictors for the incidence of all-cause mortality or non-fatal MI after multivariable adjustment for other biomarkers and clinical characteristics, whereas hsCRP, pregnancy-associated plasma protein A and sCD40L were only associated with the endpoint in univariate analysis. A multimarker model consisting of TnT, IL-10, myeloperoxidase and PlGF predicted 4-year event rates that varied between 6.0% (all markers normal) and 35.8% (three or more biomarkers abnormal). Conclusion In patients with NSTEACS, biomarkers characterising distinct aspects of the underlying atherosclerotic process and myocardial damage of the initial cardiac event can assist in predicting long-term adverse cardiac outcomes. The use of combinations of selected biomarkers adds incremental predictive value to further risk stratification in an otherwise seemingly homogeneous NSTEACS population.

Published
2011

15. Elevated Placental Growth Factor Levels Are Associated With Adverse Outcomes at Four-Year Follow-Up in Patients With Acute Coronary Syndromes

Author

Christian W. Hamm, Andreas M. Zeiher, Maarten L. Simoons, Timo Lenderink, Christopher Heeschen, Stefanie Dimmeler, Capture Study Investigators, Eric Boersma, Stephan Fichtlscherer, and Cardiology

Subjects
medicine.medical_specialty, Abciximab, CD40 Ligand, Myocardial Infarction, Myocardial Ischemia, Platelet Glycoprotein GPIIb-IIIa Complex, Pregnancy Proteins, Risk Assessment, Angina, Immunoglobulin Fab Fragments, Troponin T, Predictive Value of Tests, Internal medicine, medicine, Creatine Kinase, MB Form, Humans, Angina, Unstable, Myocardial infarction, Platelet activation, Growth Substances, Creatine Kinase, Placenta Growth Factor, Proportional Hazards Models, Randomized Controlled Trials as Topic, Proportional hazards model, business.industry, Hazard ratio, Antibodies, Monoclonal, Prognosis, medicine.disease, C-Reactive Protein, Endocrinology, Predictive value of tests, Multivariate Analysis, Cardiology, Biomarker (medicine), business, Cardiology and Cardiovascular Medicine, Biomarkers, Platelet Aggregation Inhibitors
Abstract

Objectives This study sought to evaluate the predictive value of baseline placental growth factor (PlGF) for long-term cardiovascular events in acute coronary syndromes (ACS). Background A biomarker of vascular inflammation, PlGF is identified as a powerful predictor for short-term outcome in patients with ACS. Methods In 544 patients who were enrolled in the placebo arm of the c7E3 Fab Anti Platelet Therapy in Unstable REfractory angina (CAPTURE) trial, PlGF levels were determined as well as markers of myocardial necrosis (troponin T [TnT]), general inflammation (high-sensitivity C-reactive protein [hsCRP]), and platelet activation (soluble CD40 ligand [sCD40L]). Cox proportional hazard regression analyses were applied to evaluate the relationship between biomarkers and the occurrence of all-cause death or non-fatal myocardial infarction during a median follow-up period of four years. Results Patients with PlGF levels in the fourth and fifth quintile (>27 ng/l) had higher mortality than those with lower levels (10.8% vs. 3.2%; hazard ratio [HR], 3.3; 95% confidence interval [CI], 1.6 to 7.1), as well as a higher incidence of the composite end point of death or myocardial infarction (27.6% vs. 11.3% events; HR, 2.6; 95% CI, 1.7 to 3.9). The relationship between PlGF and the composite end point remained significant after adjustment for TnT, sCD40L, and hsCRP (adjusted HR, 3.3; 95% CI, 2.0 to 5.4). Conclusions In patients with ACS, elevated plasma levels of PlGF are associated with adverse cardiac outcomes during long-term follow-up. These data suggest that PlGF as a more specific marker of vascular inflammation should be considered for risk stratification of patients with ACS rather than general markers of inflammation.

Published
2006
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16. Bleeding events with abciximab in acute coronary syndromes without early revascularization: an analysis of GUSTO IV–ACS

Author

Petr Widimsky, Witold Rużyłło, Eric Boersma, Paul W. Armstrong, Lars Wallentin, Timo Lenderink, E. Magnus Ohman, Maarten L. Simoons, and Cardiology

Subjects
Male, medicine.medical_specialty, Abciximab, medicine.medical_treatment, Myocardial Infarction, Hemorrhage, Platelet Glycoprotein GPIIb-IIIa Complex, Revascularization, Immunoglobulin Fab Fragments, Internal medicine, Angioplasty, Odds Ratio, medicine, Humans, Thrombolytic Therapy, Angioplasty, Balloon, Coronary, Coronary Artery Bypass, Aged, business.industry, Antibodies, Monoclonal, Anticoagulants, Arrhythmias, Cardiac, Syndrome, Heparin, Low-Molecular-Weight, Coronary heart disease, Surgery, Clinical trial, Logistic Models, Multivariate Analysis, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Platelet Aggregation Inhibitors, medicine.drug
Abstract

The glycoprotein IIb/IIIa receptor antagonist abciximab reduces the risk of thrombotic complications with percutaneous coronary intervention, but also has been associated with higher bleeding rates.In the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes (GUSTO IV-ACS) trial, abciximab (either a 24-hour or 48-hour infusion) was compared with placebo in 7800 patients with an acute coronary syndrome. During study drug administration, 2% of the patients underwent a revascularization procedure.In 1507 patients (19.3%), bleeding according to the Thrombolysis in Myocardial Infarction (TIMI) classification was observed while they were hospitalized or within 7 days. Ninety-eight patients (1.2%) had a major bleed, including 8 with intracranial hemorrhages. In 215 patients (2.8%), a minor bleed was reported, and in 1194 patients (15.3%), an insignificant bleed was reported. Bleeding was more frequent in patients receiving a 48-hour infusion of abciximab. Spontaneous bleeding was seen in 911 patients (11.7%). The other 596 patients had a bleeding event in conjunction with a procedure. The most significant predictors for bleeding with multivariable analysis were: use of low-molecular weight heparin, duration of abciximab infusion, region of hospitalization, performance of coronary artery bypass grafting or percutaneous coronary intervention (PCI), advanced age, and female sex. For major bleeding, the predictors were performance of coronary artery bypass grafting or PCI, long duration of abciximab administration, and advanced age.Treatment with abciximab in patients with non-ST-elevation acute coronary syndromes is safe because major bleeding and stroke are rare, and most events are clinically manageable or have few clinical consequences. Guidelines for use of abciximab in combination with other antithrombotic agents developed for PCI should also be respected in acute coronary syndromes. Specific dosing guidelines for combination with low-molecular weight heparin must be developed for patients who subsequently will undergo a PCI.

Published
2004

17. Continuous ST-segment monitoring associated with infarct size and left ventricular function in the GUSTO-I trial

Author

Peter Klootwijk, Simon H. Meij, Maarten L. Simoons, Diederick E. Grobbee, J. Dik F. Habbema, Marcel van den Brand, Karel G.M. Moons, Gerrit-Anne van Es, T. Baardman, and Timo Lenderink

Subjects
Male, medicine.medical_specialty, medicine.medical_treatment, Myocardial Infarction, Ischemia, Ventricular Function, Left, Electrocardiography, Internal medicine, medicine, Humans, ST segment, Thrombolytic Therapy, cardiovascular diseases, Myocardial infarction, Aged, Ejection fraction, medicine.diagnostic_test, business.industry, Myocardium, Liter, Thrombolysis, Middle Aged, Prognosis, medicine.disease, Intensity (physics), cardiovascular system, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Follow-Up Studies
Abstract

Background The aim of this study was to evaluate whether in patients with myocardial infarction, the intensity and duration of myocardial ischemia as measured by continuous ST monitoring are associated with infarct size and residual left ventricular function. Methods and Results The analyses included patients with myocardial infarction, receiving thrombolytic therapy, who were enrolled in the electrocardiographic substudy of GUSTO-I, monitored by a vector-derived 12-lead electrocardiographic recording system, and in whom either infarct size (defined as cumulative release of α-hydroxybutyrate dehydrogenase activity per liter of plasma over a 72-hour period [Q(72)]) or left ventricular ejection fraction (LVEF) was determined. With the use of linear regression analysis, we investigated the association of various ST-trend characteristics with Q(72) (206 patients) and with LVEF (180 patients). A higher area under the ST trend since thrombolysis until 50% ST recovery and a higher area under recurrent ischemic episodes (ST reelevations) were significantly associated with a higher Q(72), whereas only a higher area under recurrent ischemic episodes was significantly associated with a lower LVEF. These associations remained after adjusting for other patient characteristics such as age, sex, infarct location, and time to treatment. Conclusions These findings support the physiologic hypothesis that both the intensity and duration of myocardial ischemia (both reflected by the estimated areas under the ST-trend curve) determine myocardial damage and thus are associated with infarct size and ejection fraction in patients with acute myocardial infarction who receive thrombolytic therapy. (Am Heart J 1999;138:525-32.)

Published
1999

18. Comparison of usefulness of computer assisted continuous 48-h 3-lead with 12-lead ECG ischaemia monitoring for detection and quantitation of ischaemia in patients with unstable angina

Author

Gerrit-Anne van Es, Peter Klootwijk, E. J. Müller, Timo Lenderink, Simon H. Meij, Victor A. Umans, and M. L. Simoons

Subjects
Male, medicine.medical_specialty, Myocardial Ischemia, Ischemia, Sensitivity and Specificity, Angina, Electrocardiography, Internal medicine, medicine, Humans, ST segment, Angina, Unstable, Diagnosis, Computer-Assisted, Monitoring, Physiologic, Chi-Square Distribution, medicine.diagnostic_test, business.industry, Vascular disease, Unstable angina, medicine.disease, Surgery, Ambulatory, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Chi-squared distribution
Abstract

The selection of ECG leads used for ST monitoring may influence detection and quantitation of ischaemia.We compared on-line continuous 48-h 12-lead against 3-lead ST monitoring in 130 unstable angina patients (Mortara. ELI-100). Onset and offset of ST episodes were defined by the lead with the firstor = 100 microV ST change relative to baseline and the lead with the latest return to baseline ST level, respectively. ST episodes were calculated for 12 leads and 3 leads (V2, V5, III) separately.ST episodes were detected in 88 patients (77%) by 12-lead and in 71 patients (62%) by 3-lead ST monitoring (P0.02). The median number (25.75%) of episodes/patient was 1 (0.3) for 3-lead and 2 (1.6) for 12-lead (P0.0001). The total duration of ischaemia detected during 12-lead far exceeded 3-lead monitoring: 12.3 (1, 58.2) and 1.7 (0, 23.3) min respectively (P0.0001). The probability of recurrent ischaemia declined most during the first 24 h of monitoring. After a period without ST changes of 1, 12, 24 and 36 h, the probabilities of recurrent ischaemia were 63, 31, 14 and 9%, respectively.Continuous 12-lead ST monitoring increases detection rate and duration of ST episodes compared to 3-lead ST monitoring. The use of continuous 12-lead ECG monitoring devices on emergency wards and coronary care units is recommended.

Published
1997

19. Differential effects of tissue plasminogen activator and streptokinase on infarct size and on rate of enzyme release: influence of early infarct related artery patency: The GUSTO Enzyme Substudy

Author

M. L. Simoons, M. Pfisterer, G. P. Molhoek, T. Baardman, W.Th. Hermens, Timo Lenderink, and Gilles Grollier

Subjects
medicine.medical_specialty, medicine.medical_treatment, Streptokinase, Myocardial Infarction, Infarction, Myocardial Reperfusion, Tissue plasminogen activator, Ventricular Function, Left, Plasminogen Activators, Reperfusion therapy, Internal medicine, medicine, Humans, Thrombolytic Therapy, cardiovascular diseases, Myocardial infarction, Vascular Patency, Randomized Controlled Trials as Topic, business.industry, Stroke Volume, Thrombolysis, Prognosis, medicine.disease, Treatment Outcome, Tissue Plasminogen Activator, Cardiology, Cardiology and Cardiovascular Medicine, business, Fibrinolytic agent, TIMI, medicine.drug
Abstract

BACKGROUND: The recent international GUSTO trial of 41,021 patients with acute myocardial infarction demonstrated improved 90-min infarct related artery patency as well as reduced mortality in patients treated with an accelerated regimen of tissue plasminogen activator, compared to patients treated with streptokinase. A regimen combining tissue plasminogen activator and streptokinase yielded intermediate results. The present study investigated the effects of treatment on infarct size and enzyme release kinetics in a subgroup of these patients. METHODS: A total of 553 patients from 15 hospitals were enrolled in the study. Four thrombolytic strategies were compared: streptokinase with subcutaneous heparin, streptokinase with intravenous (i.v.) heparin, tissue plasminogen activator with i.v. heparin, and streptokinase plus tissue plasminogen activator with i.v. heparin. The activity of alpha-hydroxybutyrate dehydrogenase (HBDH) in plasma was centrally analysed and infarct size was defined as cumulative HBDH release per litre of plasma within 72 h of the first symptoms (Q(72)). Patency of the infarct-related vessel was determined by angiography in 159 patients, 90 min after treatment. RESULTS: Infarct size was 3.72 g-eq.1(-1) in patients with adequate coronary perfusion (TIMI-3) at the 90 min angiogram and larger in patients with TIMI-2 (4.35 g-eq.1(-1) or TIMI 0-1 (5.07 g-eq.1(-1) flow (P = 0.024). In this subset of the GUSTO angiographic study, early coronary patency rates (TIMI 2 + 3) were similar in the two streptokinase groups (53 and 46%). Higher, but similar, patency rates were observed in the tissue plasminogen activator and combination therapy groups (87 and 90%). Median infarct size for the four treatment groups, expressed in gram-equivalents (g-eq) of myocardium, was 4.4, 4.5, 3.9 and 3.9 g-eq per litre of plasma (P = 0.04 for streptokinase vs tissue plasminogen activator). Six hours after the first symptoms, respectively 5.3, 6.6, 14.0 and 13.6% of total HBDH release was complete (P < 0.0001 for streptokinase vs tissue plasminogen activator). CONCLUSIONS: Rapid and complete coronary reperfusion salvages myocardial tissue, resulting in limitation of infarct size and accelerated release of proteins from the myocardium. Treatment with tissue plasminogen activator, resulting in earlier reperfusion was more effective in reducing infarct size than the streptokinase regimens, which contributes to the differences in survival between treatment groups in the GUSTO trial.

Published
1996

20. Patients using statin treatment within 24 h after admission for ST-elevation acute coronary syndromes had lower mortality than non-users: a report from the first Euro Heart Survey on acute coronary syndromes

Author

Frans Van de Werf, Anselm K. Gitt, Maarten L. Simoons, David Hasdai, Timo Lenderink, Lars Wallentin, Shlomo Behar, Uwe Zeymer, Eric Boersma, Cardiology, and Neurosciences

Subjects
Male, medicine.medical_specialty, Acute coronary syndrome, Statin, medicine.drug_class, Myocardial Infarction, Internal medicine, Epidemiology, medicine, Humans, Angina, Unstable, Intensive care medicine, Aged, business.industry, ST elevation, Hazard ratio, Syndrome, Middle Aged, medicine.disease, Survival Analysis, Confidence interval, Treatment Outcome, Cohort, Propensity score matching, Female, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiology and Cardiovascular Medicine, business
Abstract

Statins provide effective secondary prevention in cardiovascular disease. However, it remains uncertain how soon statins should be started after an acute coronary syndrome (ACS). Recently published trials suggest starting before discharge. We hypothesize that statins should be initiated without delay.Data from a large cohort of 10,484 consecutive patients with an ACS were analysed. Of this cohort, 1426 first-time statin receivers and survivors of the first 24 h were compared with 6771 first-day survivors not receiving statin therapy. A propensity score for the likelihood of receiving statin therapy within 24 h was developed and used with other established risk factors in a multivariable analysis. There was a significantly reduced all-cause 7-day mortality in patients receiving early statin therapy [0.4 vs. 2.6%, unadjusted hazard ratio (HR) 0.16, 95% confidence interval (CI) 0.08-0.37, adjusted HR 0.34, 95% CI 0.15-0.79]. Statistical significance was observed in patients presenting with STE-ACS (adjusted HR 0.17, 95% CI 0.04-0.70) and not in NSTE-ACS patients. However, no statistical evidence of heterogeneity in treatment effect was observed between these groups.These data suggest that very early statin therapy is associated with reduced mortality in patients presenting with STE-ACS; however, these findings have to be confirmed by prospective, randomized controlled trials before firm treatment recommendations can be given.

Published
2006

21. Elevated troponin T and C-reactive protein predict impaired outcome for 4 years in patients with refractory unstable angina, and troponin T predicts benefit of treatment with abciximab in combination with PTCA

Author

Christopher Heeschen, Eric Boersma, Timo Lenderink, M. L. Simoons, Victor A. Umans, M. van den Brand, Alec Vahanian, M.J. de Boer, Christian W. Hamm, and Cardiology

Subjects
Male, medicine.medical_specialty, Abciximab, Platelet Glycoprotein GPIIb-IIIa Complex, Angina, Immunoglobulin Fab Fragments, Troponin T, Predictive Value of Tests, Internal medicine, medicine, Humans, Myocardial infarction, Angina, Unstable, Angioplasty, Balloon, Coronary, biology, Unstable angina, business.industry, C-reactive protein, Antibodies, Monoclonal, Middle Aged, medicine.disease, Troponin, Combined Modality Therapy, Survival Analysis, C-Reactive Protein, Treatment Outcome, Chronic Disease, Cardiology, biology.protein, Platelet aggregation inhibitor, Female, Cardiology and Cardiovascular Medicine, business, Platelet Aggregation Inhibitors, medicine.drug, Follow-Up Studies
Abstract

Aims Treatment with the glycoprotein IIb/IIIa receptor antagonist abciximab before and during coronary intervention in refractory unstable angina improves early outcome. We collected 4-year follow-up data to assess whether this benefit is sustained. Additionally, we investigated the predictive value of baseline troponin T and CRP for long-term cardiovascular events. Methods and Results Of 1265 patients enrolled in the CAPTURE trial follow-up was available in 94% of the patients alive after 6 months (median 48 months). Survival was similar in both groups. Both elevated troponin T and CRP were associated with impaired outcome, independently of other established risk factors, but with a different time course. Elevated troponin was associated with increased procedure related risk, and elevated CRP with increased risk for subsequent events. Lower rates of the composite end-point of death or myocardial infarction with abciximab vs. placebo were sustained during long-term follow up: 15.7% vs 17.2% at 4 years (P = ns), particularly in patients with elevated troponin T: 16.9% with abciximab vs 28.4% with placebo: P = 0.015. Elevated CRP was not associated with specific benefit of abciximab. Conclusion Troponin T as a marker of thrombosis and CRP as a marker of inflammation are independent predictors of impaired outcome at 4 years follow-up. The initial benefit from abciximab with regard to death and myocardial infarction was preserved at 4 years. No specific benefit with abciximab was observed for patients with elevated CRP, suggesting that a chronic inflammatory process is not affected by abciximab. In contrast the benefit of treatment in patients with elevated troponin T implies that the acute thrombotic process in refractory unstable angina is treated effectively.

Published
2003

22. Anticoagulant properties, clinical efficacy and safety of efegatran, a direct thrombin inhibitor, in patients with unstable angina

Author

Timo Lenderink, Rein Melkert, E. J. Müller, Victor A. Umans, M. L. Simoons, Simon H. Meij, J.W. Deckers, J. Stibbe, Peter Klootwijk, K.J. Poortermans, H. Boersma, Cardiology, and Hematology

Subjects
Adult, Male, medicine.medical_specialty, medicine.drug_class, Monitoring, Ambulatory, Thrombin time, Antithrombins, Angina, Electrocardiography, Internal medicine, Medicine, Humans, Single-Blind Method, Angina, Unstable, Aged, medicine.diagnostic_test, Dose-Response Relationship, Drug, business.industry, Unstable angina, Heparin, Anticoagulant, Anticoagulants, Middle Aged, medicine.disease, Surgery, Treatment Outcome, Direct thrombin inhibitor, Cardiology, Female, Partial Thromboplastin Time, Cardiology and Cardiovascular Medicine, business, Oligopeptides, medicine.drug, Partial thromboplastin time, Discovery and development of direct thrombin inhibitors
Abstract

Aims Thrombin plays a key role in the clinical syndrome of unstable angina. We investigated the safety and eYcacy of five dose levels of efegatran sulphate, a direct thrombin inhibitor, compared to heparin in patients with unstable angina. Methods Four hundred and thirty-two patients with unstable angina were enrolled. Five dose levels of efegatran were studied sequentially, ranging from 0·105 mg . kg "1 .h "1 to 1·2 mg . kg "1 .h "1 over 48 h. Safety was assessed clinically, with reference to bleeding and by measuring clinical laboratory parameters. EYcacy was assessed by the number of patients experiencing any episode of recurrent ischaemia as measured by computer-assisted continuous ECG ischaemia monitoring. Clinical end-points were: episodes of recurrent angina, myocardial infarction, coronary intervention (PTCA or CABG), and death. Results Efegatran demonstrated dose dependent ex-vivo anticoagulant activity with the highest dose level of 1·2 mg . kg "1 .h "1 resulting in steady state mean activated partial thromboplastin time values of approximately three times baseline. Thrombin time was also increased. Neither of the efegatran doses studied were able to suppress myocardial ischaemia during continuous ECG ischaemia monitoring to a greater extent than that seen with heparin. There were no statistically significant diVerences in clinical outcome or major bleeding between the efegatran and heparin groups. Minor bleeding and thrombophlebitis occurred more frequently in the efegatran treated patients. Conclusion Administration of efegatran sulphate at levels of at least 0·63 mg . kg "1 .h "1 provided an antithrombotic eVect which is at least comparable to an activated partial thromboplastin time adjusted heparin infusion. There was no excess of major bleeding. The level of thrombin inhibition by efegatran, as measured by activated partial thromboplastin time, appeared to be more stable than with heparin. Thus, like other thrombin inhibitors, efegatran sulphate is easier to administer than heparin. However, no clinical benefits of efegatran over heparin were apparent. (Eur Heart J 1999; 20: 1101‐1111)

Published
1999

23. Reduction of recurrent ischemia with abciximab during continuous ECG-Ischemia monitoring in patients with unstable angina refractory to standard treatment (CAPTURE)

Author

Maarten L. Simoons, Peter Klootwijk, Simon H. Meij, Timo Lenderink, Rein Melkert, and Cardiology

Subjects
Male, medicine.medical_specialty, Abciximab, Ischemia, Myocardial Infarction, Myocardial Ischemia, Placebo, Angina, Electrocardiography, Immunoglobulin Fab Fragments, Postoperative Complications, Recurrence, Physiology (medical), Internal medicine, Preoperative Care, medicine, Humans, Myocardial infarction, Angina, Unstable, Angioplasty, Balloon, Coronary, Aged, Monitoring, Physiologic, Postoperative Care, Aspirin, Unstable angina, business.industry, Standard treatment, Incidence, Antibodies, Monoclonal, Middle Aged, medicine.disease, Combined Modality Therapy, Surgery, Death, Sudden, Cardiac, Cardiology, Platelet aggregation inhibitor, Female, Cardiology and Cardiovascular Medicine, business, Platelet Aggregation Inhibitors, medicine.drug
Abstract

Background —In the CAPTURE (c7E3 Fab Anti Platelet Therapy in Unstable REfractory angina) trial, 1265 patients with refractory unstable angina were treated with abciximab or placebo, in addition to standard treatment from 16 to 24 hours preceding coronary intervention through 1 hour after intervention. To investigate the incidence of recurrent ischemia and the ischemic burden, a subset of 332 patients (26%) underwent continuous vector-derived 12-lead ECG-ischemia monitoring. Methods and Results —Patients were monitored from start of treatment through 6 hours after coronary intervention. Ischemic episodes were detected in 31 (18%) of the 169 abciximab and in 37 (23%) of the 163 placebo patients (NS). Only 9 (5%) of abciximab versus 22 (14%) of placebo patients had ≥2 ST episodes ( P P Conclusions —Recurrent ischemia predicts MI or death within 5 days of follow-up. Treatment with abciximab is associated with a reduction of frequent ischemia and a reduction of total ischemic burden in patients with refractory unstable angina. As such, patients with ischemia derive particularly high benefit from abciximab.

Published
1998

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