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1. CinE caRdiac magneTic resonAnce to predIct veNTricular arrhYthmia (CERTAINTY)

Author

Julian Krebs, Tommaso Mansi, Hervé Delingette, Bin Lou, Joao A. C. Lima, Susumu Tao, Luisa A. Ciuffo, Sanaz Norgard, Barbara Butcher, Wei H. Lee, Ela Chamera, Timm-Michael Dickfeld, Michael Stillabower, Joseph E. Marine, Robert G. Weiss, Gordon F. Tomaselli, Henry Halperin, Katherine C. Wu, and Hiroshi Ashikaga

Subjects
Medicine, Science
Abstract

Abstract Better models to identify individuals at low risk of ventricular arrhythmia (VA) are needed for implantable cardioverter-defibrillator (ICD) candidates to mitigate the risk of ICD-related complications. We designed the CERTAINTY study (CinE caRdiac magneTic resonAnce to predIct veNTricular arrhYthmia) with deep learning for VA risk prediction from cine cardiac magnetic resonance (CMR). Using a training cohort of primary prevention ICD recipients (n = 350, 97 women, median age 59 years, 178 ischemic cardiomyopathy) who underwent CMR immediately prior to ICD implantation, we developed two neural networks: Cine Fingerprint Extractor and Risk Predictor. The former extracts cardiac structure and function features from cine CMR in a form of cine fingerprint in a fully unsupervised fashion, and the latter takes in the cine fingerprint and outputs disease outcomes as a cine risk score. Patients with VA (n = 96) had a significantly higher cine risk score than those without VA. Multivariate analysis showed that the cine risk score was significantly associated with VA after adjusting for clinical characteristics, cardiac structure and function including CMR-derived scar extent. These findings indicate that non-contrast, cine CMR inherently contains features to improve VA risk prediction in primary prevention ICD candidates. We solicit participation from multiple centers for external validation.

Published
2021
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2. Baseline and Dynamic Risk Predictors of Appropriate Implantable Cardioverter Defibrillator Therapy

Author

Katherine C. Wu, Shannon Wongvibulsin, Susumu Tao, Hiroshi Ashikaga, Michael Stillabower, Timm M. Dickfeld, Joseph E. Marine, Robert G. Weiss, Gordon F. Tomaselli, and Scott L. Zeger

Subjects
cardiac magnetic resonance imaging, heart failure, risk stratification, sudden cardiac death, ventricular arrhythmia, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background Current approaches fail to separate patients at high versus low risk for ventricular arrhythmias owing to overreliance on a snapshot left ventricular ejection fraction measure. We used statistical machine learning to identify important cardiac imaging and time‐varying risk predictors. Methods and Results Three hundred eighty‐two cardiomyopathy patients (left ventricular ejection fraction ≤35%) underwent cardiac magnetic resonance before primary prevention implantable cardioverter defibrillator insertion. The primary end point was appropriate implantable cardioverter defibrillator discharge or sudden death. Patient characteristics; serum biomarkers of inflammation, neurohormonal status, and injury; and cardiac magnetic resonance‐measured left ventricle and left atrial indices and myocardial scar burden were assessed at baseline. Time‐varying covariates comprised interval heart failure hospitalizations and left ventricular ejection fractions. A random forest statistical method for survival, longitudinal, and multivariable outcomes incorporating baseline and time‐varying variables was compared with (1) Seattle Heart Failure model scores and (2) random forest survival and Cox regression models incorporating baseline characteristics with and without imaging variables. Age averaged 57±13 years with 28% women, 66% white, 51% ischemic, and follow‐up time of 5.9±2.3 years. The primary end point (n=75) occurred at 3.3±2.4 years. Random forest statistical method for survival, longitudinal, and multivariable outcomes with baseline and time‐varying predictors had the highest area under the receiver operating curve, median 0.88 (95% CI, 0.75‐0.96). Top predictors comprised heart failure hospitalization, left ventricle scar, left ventricle and left atrial volumes, left atrial function, and interleukin‐6 level; heart failure accounted for 67% of the variation explained by the prediction, imaging 27%, and interleukin‐6 2%. Serial left ventricular ejection fraction was not a significant predictor. Conclusions Hospitalization for heart failure and baseline cardiac metrics substantially improve ventricular arrhythmic risk prediction.

Published
2020
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3. 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

4. Quality of life after pharmacomechanical catheter-directed thrombolysis for proximal deep vein thrombosis

Author

Susan R. Kahn, Jim A. Julian, Clive Kearon, Chu-Shu Gu, David J. Cohen, Elizabeth A. Magnuson, Anthony J. Comerota, Samuel Z. Goldhaber, Michael R. Jaff, Mahmood K. Razavi, Andrei L. Kindzelski, Joseph R. Schneider, Paul Kim, Rabih Chaer, Akhilesh K. Sista, Robert B. McLafferty, John A. Kaufman, Brandt C. Wible, Morey Blinder, Suresh Vedantham, Michael Sichlau, Athanasios Vlahos, Steven Smith, Quinn Thalheimer, Nisha Singh, Rekha Harting, John Gocke, Scott Guth, Neel Shah, Paul Brady, Marvin Schatz, Mindy Horrow, Peyman Markazi, Leli Forouzan, Terence A.S. Matalon, David Hertzog, Swapna Goday, Margaret Kennedy, Robert Kaplan, Thomas Campbell, Jamie Hartman, Elmer Nahum, Arvind Venkat, Venkataramu Krishnamurthy, John Rectenwald, Peter Henke, Jonathan Eliason, Jonathon Willatt, Guillermo Escobar, Shaun Samuels, Barry Katzen, James Benenati, Alex Powell, Constantino Pena, Howard Wallach, Ripal Gandhi, Joseph Schneider, Stanley Kim, Farrah Hashemi, Joseph Boyle, Nilesh Patel, Michael Verta, Daniel Leung, Marc Garcia, Phillip Blatt, Jamil Khatri, Dave Epstein, Randall Ryan, Tom Sweeny, Michael Stillabower, George Kimbiris, Tuhina Raman, Paul Sierzenski, Lelia Getto, Michael Dignazio, Mark Horvath, Heather Gornik, John Bartholomew, Mehdi Shishehbor, Frank Peacock, Douglas Joseph, Soo Hyum Kim, Natalia Fendrikova Mahlay, Daniel Clair, Sean Lyden, Baljendra Kapoor, Gordon McLennon, Gregory Pierce, James Newman, James Spain, Amanjiit Gill, Aaron Hamilton, Anthony Rizzo, Woosup Park, Alan Dietzek, Ira Galin, Dahlia Plummer, Richard Hsu, Patrick Broderick, Andrew Keller, Sameer Sayeed, Dennis Slater, Herb Lustberg, Jan Akus, Robert Sidman, Mandeep Dhami, Phillip Kohanski, Anca Bulgaru, Renuka Dulala, James Burch, Dinesh Kapur, Jie Yang, Mark Ranson, Alan Wladis, David Varnagy, Tarek Mekhail, Robert Winter, Manuel Perez-Izquierdo, Stephen Motew, Robin Royd-Kranis, Raymond Workman, Scott Kribbs, Gerald Hogsette, Phillip Moore, Bradley Thomason, William Means, Richard Bonsall, John Stewart, Daniel Golwya, Ezana Azene, Wayne Bottner, William Bishop, Dave Clayton, Lincoln Gundersen, Jody Riherd, Irina Shakhnovich, Kurt Ziegelbein, Thomas Chang, Karun Sharma, Sandra Allison, Fil Banovac, Emil Cohen, Brendan Furlong, Craig Kessler, Mike McCullough, Jim Spies, Judith Lin, Scott Kaatz, Todd Getzen, Joseph Miller, Scott Schwartz, Loay Kabbani, David McVinnie, John Rundback, Joseph Manno, Richard Schwab, Randolph Cole, Kevin Herman, David Singh, Ravit Barkama, Amish Patel, Anthony Comerota, John Pigott, Andrew Seiwert, Ralph Whalen, Todd Russell, Zakaria Assi, Sahira Kazanjian, Jonathan Yobbagy, Brian Kaminski, Allan Kaufman, Garett Begeman, Robert DiSalle, Subash Thakur, Marc Jacquet, Thomas Dykes, Joseph Gerding, Christopher Baker, Mark Debiasto, Derek Mittleider, George Higgins, Steven Amberson, Roger Pezzuti, Thomas Gallagher, Robert Schainfeld, Stephan Wicky, Sanjeeva Kalva, Gregory Walker, Gloria Salazar, Benjamin Pomerantz, Virenda Patel, Christopher Kabrhel, Shams Iqbal, Suvranu Gangull, Rahmi Oklu, Scott Brannan, Sanjay Misra, Haraldur Bjarnason, Aneel Ashrani, Michael Caccavale, Chad Fleming, Jeremy Friese, John Heit, Manju Kalra, Thanila Macedo, Robert McBane, Michael McKusick, Andrew Stockland, David Woodrum, Waldemar Wysokinski, Adarsh Verma, Andrew Davis, Jerry Chung, David Nicker, Brian Anderson, Robert Stein, Michael Weiss, Parag Patel, William Rilling, Sean Tutton, Robert Hieb, Eric Hohenwalter, M. Riccardo Colella, James Gosset, Sarah White, Brian Lewis, Kellie Brown, Peter Rossi, Gary Seabrook, Marcelo Guimaraes, J. Bayne Selby, William McGary, Christopher Hannegan, Jacob Robison, Thomas Brothers, Bruce Elliott, Nitin Garg, M. Bret Anderson, Renan Uflacker, Claudio Schonholz, Laurence Raney, Charles Greenberg, John Kaufman, Frederick Keller, Kenneth Kolbeck, Gregory Landry, Erica Mitchell, Robert Barton, Thomas DeLoughery, Norman Kalbfleisch, Renee Minjarez, Paul Lakin, Timothy Liem, Gregory Moneta, Khashayar Farsad, Ross Fleischman, Loren French, Vasco Marques, Yasir Al−Hassani, Asad Sawar, Frank Taylor, Rajul Patel, Rahul Malhotra, Farah Hashemi, Marvin Padnick, Melissa Gurley, Fred Cucher, Ronald Sterrenberg, G. Reshmaal Deepthi, Gomes Cumaranatunge, Sumit Bhatla, Darick Jacobs, Eric Dolen, Pablo Gamboa, L. Mark Dean, Thomas Davis, John Lippert, Sanjeev Khanna, Brian Schirf, Jeffrey Silber, Donald Wood, J. Kevin McGraw, Lucy LaPerna, Paul Willette, Timothy Murphy, Joselyn Cerezo, Rajoo Dhangana, Sun Ho Ahn, Gregory Dubel, Richard Haas, Bryan Jay, Ethan Prince, Gregory Soares, James Klinger, Robert Lambiase, Gregory Jay, Robert Tubbs, Michael Beland, Chris Hampson, Ryan O'Hara, Chad Thompson, Aaron Frodsham, Fenwick Gardiner, Abdel Jaffan, Lawrence Keating, Abdul Zafar, Radica Alicic, Rodney Raabe, Jayson Brower, David McClellan, Thomas Pellow, Christopher Zylak, Joseph Davis, M. Kathleen Reilly, Kenneth Symington, Camerson Seibold, Ryan Nachreiner, Daniel Murray, Stephen Murray, Sandeep Saha, Gregory Luna, Kim Hodgson, Robert McLafferty, Douglas Hood, Colleen Moore, David Griffen, Darren Hurst, David Lubbers, Daniel Kim, Brent Warren, Jeremy Engel, D.P. Suresh, Eric VanderWoude, Rahul Razdan, Mark Hutchins, Terry Rounsborg, Madhu Midathada, Daniel Moravec, Joni Tilford, Joni Beckman, Mahmood Razavi, Kurt Openshaw, D. Preston Flanigan, Christopher Loh, Howard Dorne, Michael Chan, Jamie Thomas, Justin Psaila, Michael Ringold, Jay Fisher, Any Lipcomb, Timothy Oskin, Brandt Wible, Brendan Coleman, David Elliott, Gary Gaddis, C. Doug Cochran, Kannan Natarajan, Stewart Bick, Jeffrey Cooke, Ann Hedderman, Anne Greist, Lorrie Miller, Brandon Martinez, Vincent Flanders, Mark Underhill, Lawrence Hofmann, Daniel Sze, William Kuo, John Louie, Gloria Hwang, David Hovsepian, Nishita Kothary, Caroline Berube, Donald Schreiber, Brooke Jeffrey, Jonathan Schor, Jonathan Deitch, Kuldeep Singh, Barry Hahn, Brahim Ardolic, Shilip Gupta, Riyaz Bashir, Angara Koneti Rao, Manish Garg, Pravin Patil, Chad Zack, Gary Cohen, Frank Schmieder, Valdimir Lakhter, David Sacks, Robert Guay, Mark Scott, Karekin Cunningham, Adam Sigal, Terrence Cescon, Nick Leasure, Thiruvenkatasamy Dhurairaj, Patrick Muck, Kurt Knochel, Joann Lohr, Jose Barreau, Matthew Recht, Jayapandia Bhaskaran, Ranga Brahmamdam, David Draper, Apurva Mehta, James Maher, Melhem Sharafuddin, Steven Lentz, Andrew Nugent, William Sharp, Timothy Kresowik, Rachel Nicholson, Shiliang Sun, Fadi Youness, Luigi Pascarella, Charles Ray, Martha-Gracia Knuttinen, James Bui, Ron Gaba, Valerie Dobiesz, Ejaz Shamim, Sangeetha Nimmagadda, David Peace, Aarti Zain, Alison Palumto, Ziv Haskal, Jon Mark Hirshon, Howard Richard, Avelino Verceles, Jade Wong-You-Chong, Bertrand Othee, Rahul Patel, Bogdan Iliescu, David Williams, Joseph Gemmete, Wojciech Cwikiel, Kyung Cho, James Schields, Ranjith Vellody, Paula Novelli, Narasimham Dasika, Thomas Wakefield, Jeffrey Desmond, James Froehlich, Minhajuddin Khaja, David Hunter, Jafar Golzarian, Erik Cressman, Yvonne Dotta, Nate Schmiechen, John Marek, David Garcia, Isaac Tawil, Mark Langsfeld, Stephan Moll, Matthew Mauro, Joseph Stavas, Charles Burke, Robert Dixon, Hyeon Yu, Blair Keagy, Kyuny Kim, Raj Kasthuri, Nigel Key, Michael Makaroun, Robert Rhee, Jae−Sung Cho, Donald Baril, Luke Marone, Margaret Hseih, Kristian Feterik, Roy Smith, Geetha Jeyabalan, Jennifer Rogers, Russel Vinik, Dan Kinikini, Larry Kraiss, Michelle Mueller, Robert Pendleton, Matthew Rondina, Mark Sarfati, Nathan Wanner, Stacy Johnson, Christy Hopkins, Daniel Ihnat, John Angle, Alan Matsumoto, Nancy Harthun, Ulku Turba, Wael Saad, Brian Uthlaut, Srikant Nannapaneni, David Ling, Saher Sabri, John Kern, B. Gail Macik, George Hoke, Auh Wahn Park, James Stone, Benjamin Sneed, Scott Syverud, Kelly Davidson, Aditya Sharma, Luke Wilkins, Carl Black, Mark Asay, Daniel Hatch, Robert Smilanich, Craig Patten, S. Douglas Brown, Ryan Nielsen, William Alward, John Collins, Matthew Nokes, Randolph Geary, Matthew Edwards, Christopher Godshall, Pavel Levy, Ronald Winokur, Akhilesh Sista, David Madoff, Kyungmouk Lee, Bradley Pua, Maria DeSancho, Raffaele Milizia, Jing Gao, Gordon McLean, Sanualah Khalid, Larry Lewis, Nael Saad, Mark Thoelke, Robert Pallow, Seth Klein, Gregorio Sicard, Heather L. Gornik, Jim Julian, Stephen Kee, Lawrence Lewis, Elizabeth Magnuson, and Timothy P. Murphy

Subjects
Adult, Male, medicine.medical_specialty, Time Factors, Mechanical Thrombolysis, medicine.medical_treatment, Catheter directed thrombolysis, 030204 cardiovascular system & hematology, Iliac Vein, Article, law.invention, 03 medical and health sciences, 0302 clinical medicine, Fibrinolytic Agents, Quality of life, Randomized controlled trial, law, Surveys and Questionnaires, Internal medicine, Epidemiology, Medicine, Humans, In patient, Thrombolytic Therapy, 030212 general & internal medicine, cardiovascular diseases, Thrombus, Venous Thrombosis, business.industry, Thrombolysis, Femoral Vein, Middle Aged, medicine.disease, United States, humanities, 3. Good health, Venous thrombosis, Treatment Outcome, Quality of Life, Female, Surgery, Cardiology and Cardiovascular Medicine, business
Abstract

After deep venous thrombosis (DVT), many patients have impaired quality of life (QOL). We aimed to assess whether pharmacomechanical catheter-directed thrombolysis (PCDT) improves short-term or long-term QOL in patients with proximal DVT and whether QOL is related to extent of DVT.The Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis (ATTRACT) trial was an assessor-blinded randomized trial that compared PCDT with no PCDT in patients with DVT of the femoral, common femoral, or iliac veins. QOL was assessed at baseline and 1 month, 6 months, 12 months, 18 months, and 24 months using the Venous Insufficiency Epidemiological and Economic Study on Quality of Life/Symptoms (VEINES-QOL/Sym) disease-specific QOL measure and the 36-Item Short Form Health Survey (SF-36) physical component summary (PCS) and mental component summary general QOL measures. Change in QOL scores from baseline to assessment time were compared in the PCDT and no PCDT treatment groups overall and in the iliofemoral DVT and femoral-popliteal DVT subgroups.Of 692 ATTRACT patients, 691 were analyzed (mean age, 53 years; 62% male; 57% iliofemoral DVT). VEINES-QOL change scores were greater (ie, better) in PCDT vs no PCDT from baseline to 1 month (difference, 5.7; P = .0006) and from baseline to 6 months (5.1; P = .0029) but not for other intervals. SF-36 PCS change scores were greater in PCDT vs no PCDT from baseline to 1 month (difference, 2.4; P = .01) but not for other intervals. Among iliofemoral DVT patients, VEINES-QOL change scores from baseline to all assessments were greater in the PCDT vs no PCDT group; this was statistically significant in the intention-to-treat analysis at 1 month (difference, 10.0; P .0001) and 6 months (8.8; P .0001) and in the per-protocol analysis at 18 months (difference, 5.8; P = .0086) and 24 months (difference, 6.6; P = .0067). SF-36 PCS change scores were greater in PCDT vs no PCDT from baseline to 1 month (difference, 3.2; P = .0010) but not for other intervals. In contrast, in femoral-popliteal DVT patients, change scores from baseline to all assessments were similar in the PCDT and no PCDT groups.Among patients with proximal DVT, PCDT leads to greater improvement in disease-specific QOL than no PCDT at 1 month and 6 months but not later. In patients with iliofemoral DVT, PCDT led to greater improvement in disease-specific QOL during 24 months.

Published
2020

5. Ischemic Events Occur Early in Patients Undergoing Percutaneous Coronary Intervention and Are Reduced With Cangrelor: Findings From CHAMPION PHOENIX

Author

Matthew A. Cavender, Robert A. Harrington, Gregg W. Stone, Ph. Gabriel Steg, C. Michael Gibson, Christian W. Hamm, Matthew J. Price, Renato D. Lopes, Sergio Leonardi, Efthymios N. Deliargyris, Jayne Prats, Kenneth W. Mahaffey, Harvey D. White, Deepak L. Bhatt, Kurt Huber, Valter C. Lima, Julia B. Jorgova-Makedonska, Petr Widimský, Bondo Kobulia, Peter W. Radke, Ezio Bramucci, Adam Witkowski, Evgeny Shlyakhto, Frans Van de Werf, David P. Faxon, E. Magnus Ohman, Freek W.A. Verheugt, W. Douglas Weaver, Jan G.P. Tijssen, Matthew Wilson, Stacey Mangum, Chiara Melloni, Matthew J. Brennan, Pierluigi Tricoci, Robert Harrison, Pedro Barros, Luciana Armaganijan, Monique Anderson, Akshay Bagai, Philippe Généreux, Sorin J. Brener, Laura LaSalle, Werner Benzer, Georg Delle-Karth, Franz Leisch, Jamil Abdalla Saad, Alexandre Abizaid, Carlos Augusto Formiga Areas, Expedito E. Ribeiro, Fabio Rossi Dos Santos, Rogerio Tadeu Tumelero, Roberto Vieira Botelho, Borislav Atzev, Boicho Boichev, Georgi Grigorov, Nikolay Penkov, Ivo Petrov, Boris Zehirov, Pavel Cervinka, Zdenek Coufal, Petr Hajek, David Horak, Petr Kala, Petr Kmonicek, Viktor Kocka, Jan Mrozek, Stanislav Simek, Jan Sitar, Josef Stasek, Frantisek Tousek, Gulnara Chapidze, Nodar Emukhvari, George Khabeishvili, Merab Mamatsashvili, Tamaz Shaburishvili, Steffen Behrens, Harald Darius, Martin Dissmann, Stephan Fichtlscherer, Wolfgang Franz, Tobias Geisler, Sabine Genth-Zotz, Britta Goldmann, Hubertus Heuer, Stefan Hoffmann, Andreas Mugge, Tudor Poerner, Peter Radke, Gert Richardt, Christoph Stellbrink, Nikos Werner, Stefano De Servi, Gennaro Galasso, Alberto Menozzi, Giuseppe Musumeci, Andrea Picchi, Patrizia Presbitero, Gerard Devlin, Alexander Sasse, Douglas Scott, Ralph Stewart, Szyszka Andrzej, Witold Dubaniewicz, Zbigniew Gasior, Jaroslaw Kasprzak, Andrzej Kleinrok, Zdzislawa Kornacewicz-Jach, Andrzej Rynkiewicz, Cezary Sosnowski, Radoslaw Targonski, Jaroslaw Trebacz, Elzbieta Zinka, Olga Barbarash, Yakov Dovgalevsky, Ivan Gordeev, Svetlana Kalinina, Elena Kosmachova, Valentin Markov, Prokhor Pavlov, Sergey Shalaev, Zaur Shogenov, Irina Sukmanova, Elena Vasilieva, Alexey Yakovlev, Sarana Boonbaichaiyapruck, Noppadol Chamnarnphol, Pinij Kaewsuwanna, Srun Kuanprasert, Dilok Piyayotai, Maged Amine, Dominick Angiolillo, Imran Arif, James Blankenship, Emmanouil Brilakis, Michael Chan, Joseph Cinderella, Brent Davis, Chandanreddy Devireddy, Mark Dorogy, John Douglas, Norman Ferrier, Daniel Fisher, Robert Foster, William French, John Galla, Lawrence Gimple, Harinder Gogia, Prospero Gogo, Raghava Gollapudi, Luis Gruberg, James Hermiller, Richard Heuser, Robert Iwaoka, Zubair Jafar, Carey Kimmelstiel, Scott Kinlay, James Leggett, Pierre Leimgruber, Dustin Letts, Michael Lipsitt, Reginald Low, Joaquin Martinez-Arraras, Marc Mayhew, Brent McLaurin, Paul McWhirter, Ayoub Mirza, Brian Negus, Thomas Nygaard, William O’Riordan, Richard Paulus, John Petersen, Hector Picon, Mark Picone, Ernesto Rivera, David Rizik, Arsenio Rodriguez, Jorge Saucedo, J. Christopher Scott, Virender Sethi, Adhir Shroff, Craig Siegel, Douglas Spriggs, Daniel Steinberg, Michael Stillabower, Thomas Stuckey, Jose Suarez, Jeffrey Tauth, Dogan Temizer, Mladen Vidovich, Michele Voeltz, Jonathan Waltman, Michael Wilensky, ACS - Heart failure & arrhythmias, and Cardiology

Subjects
percutaneous coronary intervention, P2Y12 receptor antagonist, Original Articles, Adenosine Monophosphate, Clopidogrel, Coronary Interventions, Treatment Outcome, myocardial infarction, Purinergic P2Y Receptor Antagonists, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Humans, Cardiology and Cardiovascular Medicine, Platelet Aggregation Inhibitors, coronary artery disease, thrombosis
Abstract

Supplemental Digital Content is available in the text., Background: Thrombotic events are reduced with cangrelor, an intravenous P2Y12 inhibitor. We sought to characterize the timing, number, and type of early events (within 2 hours of randomization) in CHAMPION PHOENIX (A Clinical Trial Comparing Cangrelor to Clopidogrel Standard of Care Therapy in Subjects Who Require Percutaneous Coronary Intervention). Methods: CHAMPION PHOENIX was a double-blind, placebo-controlled trial that randomized patients undergoing percutaneous coronary intervention to cangrelor or clopidogrel. For this analysis, we evaluated the efficacy of cangrelor in the first 2 hours postrandomization with regards to the primary end point (death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis). Sensitivity analyses were performed evaluating a secondary, post hoc end point (death, Society of Coronary Angiography and Intervention myocardial infarction, ischemia-driven revascularization, or Academic Research Consortium definite stent thrombosis). Results: The majority of events (63%) that occurred in the trial occurred within 2 hours of randomization. The most common early event was myocardial infarction; next were stent thrombosis, ischemia driven revascularization, and death. In the first 2 hours after randomization, cangrelor significantly decreased the primary composite end point compared with clopidogrel (4.1% versus 5.4%; hazard ratio, 0.76 [95% CI, 0.64–0.90], P=0.002). Similar findings were seen for the composite end point of death, Society of Coronary Angiography and Intervention myocardial infarction, ischemia-driven revascularization, or Academic Research Consortium stent thrombosis at 2 hours (0.9% versus 1.6%; hazard ratio, 0.57 [95% CI, 0.40–0.80], P=0.001). Between 2 and 48 hours, there was no difference in the primary composite end point (0.6% versus 0.5%; odds ratio, 1.17 [95% CI, 0.71–1.93]; P=0.53). Early (≤2 hours of randomization) GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) moderate or severe bleeding events were infrequent, and there was no significant difference with cangrelor compared with clopidogrel (0.2% [n=10] versus 0.1% [n=4]; adjusted odds ratio, 1.41 [95% CI, 0.37–5.40]; P=0.62). Conclusions: The reductions in ischemic events and overall efficacy seen with cangrelor in CHAMPION PHOENIX occurred early and during the period of time in which patients were being actively treated with cangrelor. These findings provide evidence that supports the importance of potent platelet inhibition during percutaneous coronary intervention. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01156571.

Published
2021

6. Cangrelor With and Without Glycoprotein IIb/IIIa Inhibitors in Patients Undergoing Percutaneous Coronary Intervention

Author

Muthiah Vaduganathan, Robert A. Harrington, Gregg W. Stone, Efthymios N. Deliargyris, Ph. Gabriel Steg, C. Michael Gibson, Christian W. Hamm, Matthew J. Price, Alberto Menozzi, Jayne Prats, Steven Elkin, Kenneth W. Mahaffey, Harvey D. White, Deepak L. Bhatt, Fernando Cura, Miguel Ballarino, Anibal Agustín Damonte, Diego Grinfeld, Carlos Alejandro Álvarez, Alberto Fernandez, Ahmad Farshid, Brendan Gunalingam, Craig Jeurgens, Harry Lowe, Hisham Hallani, Greg Nelson, Gishel New, Ronald Dick, Jeffrey Lefkovits, Stephen Duffy, Nick Bett, Raibhan Yadav, Paul Garrahy, Ron Lehman, Philip Aylward, John Horowitz, Matthew Worthley, David Cross, Jaime Rankin, Peter Thompson, Phil Roberts-Thomson, Rohan Jayasinghe, Con Aroney, Kurt Huber, Franz Leisch, Johann Altenberger, Georg Gaul, Thomas Neunteufl, Franz Weidinger, Herwig Schuchlenz, Heinrich Weber, Werner Benzer, Paulo Rossi, Breno Almeida, Antonio Godinho, Fabio Vilas-Boas, Luciano Vacanti, Renato Serpa, José Antonio Jatene, Gilmar Reis, Jamil Saad, Marcos Marino, Roberto Botelho, Constantino Costantini, Ricardo Wang, Dalton Precoma, Miguel Rati, Luis Bodanese, Euler Manenti, João Paulo Zouvi, Rogerio Tumelero, Arthur Herdy, Eulogio Martinez Filho, Antônio Carvalho, Roberto Franken, Lawrence Title, Charles Lazzam, Francois Reeves, Tamaz Shaburishvili, Gulnara Chapidze, Merab Mamatsashvili, Irakli Khintibidze, Hubertus Heuer, Hans-Georg Olbrich, Sabine Genth-Zotz, Sven Moebius-Winkler, Michael Buerke, Stefan Hoffmann, Peter Radke, Helge Moellmann, Hugo Katus, Hans-Friedrich Voehringer, Christian Hengstenberg, Volker Klauss, Johannes Brachmann, Aftab Khan, Sampath Kumar, Padinhare Mohanan, Praveen Chandra, Maddury Rao, S.S. Ramesh, Keyur Parikh, Arun Srinivas, Nakul Sinha, V.S. Prakash, Shirish Hiremath, Anil Mishra, Sanjeeb Roy, Kamal Sethi, Ashwani Mehta, Tejas Patel, Suman Bhandari, Milind Gadkari, Stefano De Servi, Giuseppe Musumeci, Bernardo Cortese, Giancarlo Marenzi, Raffaele De Caterina, Ralph Stewart, Gerard Devlin, Scott Harding, John Elliott, Gerard Wilkins, Douglas Scott, Slawomir Dobrzycki, Waldemar Dorniak, Dariusz Dudek, Zbigniew Gasior, Jaroslaw Hiczkiewicz, Zdzislawa Kornacewicz-Jach, Leszek Kubik, Krzysztof Kuc, Jerzy Kuzniar, Walentyna Mazurek, Jakub Ostrowski, Michal Tendera, Andrzej Wisniewski, Elzbieta Zinka, Krzysztof Zmudka, Jana Pawła, Maciej Kosmider, null Seweryna, Andres Iñiguez, Rafael Melgares, Francisco Goicolea, Jose Hernandez, Javier Zueco, Igor Kraiz, Mykola Vatutin, Anatoliy Polyakov, Yury Sokolov, Kenneth House, Charles Campbell, Timothy Trageser, Kenneth Baran, Neal Kleiman, Roberto Medina, Roger Hill, M. Zubair Jafar, David Drenning, Herbert Ladley, Ahed Nahhas, Alan Niederman, Amit Goyal, William Abernethy, Naseem Jaffrani, Richard Zelman, Brian Negus, Jose Marquez, Ehtisham Mahmud, William French, John Paulowski, Charles Pollack, Mark Mines, Robert Federici, Marc Schweiger, Kalim Habet, Ofsman Quintana, Thomas Nygaard, Steve Orlow, Douglas Spriggs, Ivan Chavez, Mark Warner, Richard Paulus, David Cochran, Cary Hirsch, Ajay Virmani, Peter Soukas, Nalin Srivastava, L. Norman Ferrier, Annapoorna Kini, Mark Greenberg, Howard Herrmann, Valerian Fernandes, Barry Bertolet, Ron Waksman, Joseph Henderson, Harinder Gogia, Maged Amine, Kourosh Mastali, Thomas Stuckey, Peter Hui, Luigi Pacifico, Todd Caulfield, Wilson Ginete, William Ballard, Robert Iwaoka, Joseph Stella, Vijay Misra, Costa Andreou, Michele Voeltz, Wayne Batchelor, Cezar Staniloae, Sanford Gips, Jeffrey Kramer, Paul Mahoney, John Wang, Prospero Gogo, David Rizik, Rex Winters, Garry MacKenzie, Stephen Jenkins, Paul Teirstein, Pierre Leimgruber, J. Christopher Scott, Seth Krauss, Steven Rohrbeck, Robert Martin, Gustavo Grieco, Louis Cannon, Don Westerhausen, F. David Fortuin, Steven Schulman, Joel Cohn, Brent McLaurin, Jorge Saucedo, Robert Wozniak, Jack Hall, Kevin Marzo, Merrill Krolick, Lawrence Gimple, Eric Hockstad, Arsenio Rodriguez, John Kao, Adhir Shroff, Michael Attubato, Ramon Quesada, Ernesto Rivera, Dean Kereiakes, Russell Raymond, Thomas Amidon, David Lee, Spencer King, John Douglas, Abnash Jain, J. Patrick Kleaveland, Mitchell Driesman, Krishna Kumar, Glen Kowalchuk, Behzad Taghizadeh, Lawrence Barr, Keith Benzuly, Tarek Helmy, Duane Pinto, Joseph Aragon, Reginald Low, Phillip Horwitz, Thomas LeGalley, Dominick Angiolillo, Rajesh Sachdeva, Kenneth Kent, Luis Gruberg, Richard Bach, Thomas Pow, Charles O'Shaughnessy, Shing Wong, Saeed R. Shaikh, Arthur Reitman, Mark Lawrence, Alejandro Garcia Escudero, Carlos Poy, Miguel Miceli, Antonio Pocovi, Hugo Londero, Jorge Baccaro, Leonid Polonetsky, Aliaksey Karotkin, Leanid Shubau, Eduardo Maffini, Bruno Machado, José Airton, Valter Lima, Jose Jatene, Marco Perin, Paulo Caramori, Iran Castro, Ivan Manukov, Mladen Grigorov, Plamen Milkov, Julia Jorgova, Svetoslav Georgiev, Nizar Rifai, Alexander Doganov, Ivo Petrov, William Hui, Jean-Francois Tanguay, Marek Richter, Frantisek Tousek, Zdenek Klimsa, Michal Padour, Jan Mrozek, Marian Branny, Zdenek Coufal, Stanislav Simek, Vladimir Rozsival, Leos Pleva, Josef Stasek, Petr Kala, Ladislav Groch, Viktor Kocka, Rajesh Jain, Darshan Banker, Lanka Krishna, Hasit Joshi, Jaspal Arneja, Virgilijus Grinius, Sigute Norkiene, Birute Petrauskiene, Rolf Michels, Melvin Tjon, Hans de Swart, Robbert de Winter, Harvey White, Malcolm Abernethey, Alexander Osiev, Kirill Linev, Svetlana Kalinina, Svetlana Baum, Elena Kosmachova, Zaur Shogenov, Valentin Markov, Svetlana Boldueva, Olga Barbarash, Victor Kostenko, Elena Vasilieva, Aleksey Gruzdev, Victor Lusov, Pavel Dovgalevsky, Oleg Azarin, Sergey Chernov, Olga Smolenskaya, Alexey Duda, Viliam Fridrich, Marian Hranai, Martin Studenčan, Peter Kurray, John Bennett, Pieter Blomerus, Laurence Disler, Johannes Engelbrecht, Eric Klug, Robert Routier, Tjaart Venter, Nico Van Der Merwe, Anthony Becker, Kwang-Soo Cha, Seung-Hwan Lee, Sang-Jin Han, Tae Jin Youn, Seung-Ho Hur, Hong Seog Seo, Hun-Sik Park, Chong-Yun Rhim, Wook-Bum Pyun, Hyunmin Choe, Myung-Ho Jeong, Jong-Seon Park, Eak-Kyun Shin, Felipe Hernández, Jaume Figueras, Rosana Hernández, José Ramón López-Minguez, José Ramón González Juanatey, Ramón López Palop, Guillermo Galeote, Noppadol Chamnarnphol, Wacin Buddhari, Nakarin Sansanayudh, Srun Kuanprasert, William Penny, Charles Lui, Garfield Grimmett, Venkatraman Srinivasan, Kevin Ariani, Waqor Khan, James Blankenship, Steven Eisenberg, Jerry Greenberg, Jeffrey Breall, Harish Chandna, Paul Tolerico, Georges Nseir, Adam Greenbaum, Pierre Istfan, Joel Sklar, Robert Smith, Nicholaos Xenopoulos, Mahesh Mulumudi, James Hoback, Gregory Eaton, John Griffin, Ramin Ebrahimi, Robert Lundstrom, Dogan Temizer, Kenneth Tam, Jose Suarez, Amish Raval, Jay Kaufman, Emmanouil Brilakis, Michael Stillabower, Kathleen Quealy, Boris Nunez, Bruce Samuels, Agustin Argenal, Vankeepuram Srinivas, Andrew Rosenthal, Pradyumna Tummala, Paul Myers, Nelson LaMarche, Michael Chan, Daniel Simon, Richard Kettelkamp, Gary Schaer, Edward Kosinski, Maurice Buchbinder, Mukesh Sharma, Mark Goodwin, J. Tift Mann, David Holmes, Sunil Rao, Michael Azrin, Roger Gammon, Kreton Mavromatis, Abdel Ahmed, Marcel Zughaib, R. Jeffrey Westcott, Ash Jain, Georg Delle-Karth, Jamil Abdalla Saad, Alexandre Abizaid, Carlos Augusto Formiga Areas, Expedito E. Ribeiro, Fabio Rossi Dos Santos, Rogerio Tadeu Tumelero, Roberto Vieira Botelho, Borislav Atzev, Boicho Boichev, Georgi Grigorov, Nikolay Penkov, Boris Zehirov, Pavel Cervinka, Petr Hajek, David Horak, Petr Kmonicek, Jan Sitar, Nodar Emukhvari, George Khabeishvili, Steffen Behrens, Harald Darius, Martin Dissmann, Stephan Fichtlscherer, Wolfgang Franz, Tobias Geisler, Britta Goldmann, Andreas Mugge, Tudor Poerner, Gert Richardt, Christoph Stellbrink, Nikos Werner, Ezio Bramucci, Gennaro Galasso, Andrea Picchi, Patrizia Presbitero, Alexander Sasse, Szyszka Andrzej, Witold Dubaniewicz, Jaroslaw Kasprzak, Andrzej Kleinrok, Andrzej Rynkiewicz, Cezary Sosnowski, Radoslaw Targonski, Jaroslaw Trebacz, Adam Witkowski, Yakov Dovgalevsky, Ivan Gordeev, Prokhor Pavlov, Sergey Shalaev, Irina Sukmanova, Alexey Yakovlev, Sarana Boonbaichaiyapruck, Pinij Kaewsuwanna, Dilok Piyayotai, Imran Arif, Joseph Cinderella, Brent Davis, Chandanreddy Devireddy, Mark Dorogy, Norman Ferrier, Daniel Fisher, Robert Foster, John Galla, Raghava Gollapudi, James Hermiller, Richard Heuser, Zubair Jafar, Carey Kimmelstiel, Scott Kinlay, James Leggett, Dustin Letts, Michael Lipsitt, Joaquin Martinez-Arraras, Marc Mayhew, Paul McWhirter, Ayoub Mirza, William O'Riordan, John Petersen, Hector Picon, Mark Picone, Matthew Price, Virender Sethi, Craig Siegel, Daniel Steinberg, Jeffrey Tauth, Mladen Vidovich, Jonathan Waltman, and Michael Wilensky

Subjects
Male, medicine.medical_specialty, Ticlopidine, medicine.medical_treatment, Myocardial Ischemia, Hemorrhage, Platelet Glycoprotein GPIIb-IIIa Complex, 030204 cardiovascular system & hematology, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cangrelor, P2Y12, Double-Blind Method, Internal medicine, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Angioplasty, Balloon, Coronary, Infusions, Intravenous, Aged, Aspirin, business.industry, Percutaneous coronary intervention, Middle Aged, Clopidogrel, Adenosine Monophosphate, Surgery, Treatment Outcome, chemistry, Glycoprotein IIb/IIIa inhibitors, Conventional PCI, Eptifibatide, Cardiology, Platelet aggregation inhibitor, Drug Therapy, Combination, Female, Cardiology and Cardiovascular Medicine, business, Platelet Aggregation Inhibitors, medicine.drug
Abstract

Background Cangrelor, an intravenous, reversible P2Y12 antagonist, is approved for use in patients undergoing percutaneous coronary intervention (PCI). Objectives This study sought to evaluate the efficacy and safety of cangrelor compared with clopidogrel in subgroups that did and did not receive glycoprotein IIb/IIIa inhibitors (GPIs). Methods This pooled, patient-level analysis of the 3 CHAMPION (Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) trials analyzed all randomized patients who underwent PCI and received the study drug (n = 24,902). Only bailout/rescue GPI use was permitted, except in CHAMPION PCI, in which routine or bailout/rescue GPI use was at the site investigator’s discretion. The primary efficacy endpoint was the composite of all-cause mortality, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 h after randomization. Results Overall, 3,173 patients (12.7%) received a GPI, most commonly eptifibatide (69.4%). Despite variation in indications for GPIs, baseline characteristics were well balanced between the cangrelor and clopidogrel arms in subsets receiving and not receiving GPIs. Rates of the primary composite endpoint were lower with cangrelor compared with clopidogrel in patients who did (4.9% vs. 6.5%; odds ratio [OR]: 0.74; 95% confidence interval [CI]: 0.55 to 1.01) or did not receive a GPI (3.6% vs. 4.4%; OR: 0.82; 95% CI: 0.72 to 0.94; Pint = 0.55). Cangrelor did not increase the primary safety endpoint, GUSTO-defined severe/life-threatening bleeding, in patients who did (0.4% vs. 0.5%; OR: 0.71; 95% CI: 0.25 to 1.99) or did not receive GPIs (0.2% vs. 0.1%; OR: 1.56; 95% CI: 0.80 to 3.04; Pint = 0.21). GPI use was associated with increased risk of bleeding in both treatment arms. Conclusions Cangrelor’s efficacy in reducing ischemic complications in patients undergoing PCI was maintained irrespective of GPI administration. GPI use was associated with substantially higher bleeding rates, regardless of the randomization to cangrelor or clopidogrel. (A Clinical Trial to Demonstrate the Efficacy of Cangrelor [PCI]: NCT00305162 ; Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition [PLATFORM]: NCT00385138 ; A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention [PCI] [CHAMPION PHOENIX] [CHAMPION]: NCT01156571 )

Published
2017

7. Abstract 41: Broken Heart Syndrome-'Not so rare anymore'

Author

Anitha Rajamanickam, Pranav Kansara, Zaher Fanari, Abhishek D Rao, James Hopkins, Ehsanur Rahman, Michael Kostal, Michael Stillabower, and Weintraub William

Subjects
Cardiology and Cardiovascular Medicine
Abstract

Background: Takotsubo or stress induced cardiomyopathy (TCM), once considered rare is now an increasingly considered differential diagnosis in patients presenting as an acute myocardial infarction (MI). TCM is a rapidly reversible form of acute heart failure associated with a distinctive left ventricular contraction pattern and non-obstructive( Methods: Medical records were reviewed for patients, from 2006 onwards, with either a discharge diagnosis of TCM or a clinical presentation of ST elevation MI (STEMI) or a Non-STEMI (NSTEMI) and with ventriculogram on cardiac catheterizations (CC) but without any coronary interventions. We retrieved 972 patients and 99 met the criteria for TCM after a detailed review of their records. Findings: Our data showed that the diagnosis of TCM increased yearly from 2006 to 2011 presumably due to an increasing awareness of this entity. In 2011, 25 of 937 patients presumed to be a STEMI/NSTEMI were TCM (incidence of 2.7%). TCM patients were more likely to be older female patients (See figure for Demographics). A stressful trigger could be identified in 45 patients, the most common causes being death in the family, diagnosis of cancer or recent illness/surgery. Comorbidities included hypertension (57%), hyperlipidemia (55%), depression/anxiety(34%) , diabetes(22%), active smoking(16%) and chronic pain (24%).Follow up ECHO were available only in 69% and of theses completely recovery was seen in 73% ,partial recovery in 23% and minimal or no recovery in 4% of patients. All patients who showed no recovery had TCM in the postoperative period. Mortality was 5% during index hospitalization and all these patients were ICU patients (either postoperative or septic shock patients) Conclusions: TCM is becoming an increasing finding in the cardiac catheterization lab in patients presenting as an acute MI .Increasing awareness of this condition and performing a ventriculogram in these patients is necessary for diagnosis. Our study suggests that in ICU patients, a diagnosis of TCM portends a poor prognosis and TCM in the postoperative period may result in permanent cardiomyopathy.

Published
2013

8. Abstract 318: Takotsubos Cardiomyopathy-EKG presentations

Author

Anitha Rajamanickam, Pranav Kansara, Zaher Fanari, Abhishek D Rao, James Hopkins, Ehsanur Rahman, Edward Goldenbeg, Michael Kostal, Michael Stillabower, and William Weintraub

Subjects
Cardiology and Cardiovascular Medicine
Abstract

Background: In patients presenting with a clinical picture of acute myocardial infarction (MI), Stress induced or Takotsubos cardiomyopathy (TCM), once considered rare is now an increasingly considered differential diagnosis. Literature regarding this disease is relatively scarce. We aimed to review the electrocardiogram (EKG ) presentation of these patients. Methods: Medical records were reviewed for patients, from 2006 onwards, with either a discharge diagnosis of TCM or with a clinical presentation of acute MI and with ventriculogram on cardiac catheterizations (CC) but without any coronary interventions. We retrieved 972 patients and of those 99 met the criteria for TCM after a detailed review of their records Results: ST elevations were seen on EKG in 20% of patients-15 patients were initially considered a STEMI and another 5 were considered a possible STEMI .80% presented as unstable angina or a NTEMI with elevated troponins and of these 50% showed t wave changes suggestive of ischemia on EKG. Of the STEMI, 6 showed ST elevations in the anterior or anteroseptal leads, 7 showed ST elevations in the lateral or anterolateral leads, 4 showed ST elevations in the inferior leads and 3 showed diffuse ST segment elevations. Only one patient showed the classic reciprocal ST segment depression on EKG. However, the type of EKG presentations did not affect in hospital mortality or recovery of LV function Conclusions: Most TCM patients who present like a STEMI have ST segment elevations without the classical ST reciprocal depressions. They also present with higher Troponin and CKMB values, similar to STEMI due to obstructive CAD, than patients who present like a NSTEMI. However this did not appear to influence in hospital mortality or recovery of LV function.

Published
2013

9. Celecoxib does not alter cardiovascular and renal function during dietary salt loading

Author

Megan M, Wenner, David G, Edwards, Chester A, Ray, William C, Rose, Timothy J, Gardner, Michael, Stillabower, and William B, Farquhar

Subjects
Adult, Sulfonamides, Cyclooxygenase 2 Inhibitors, Angiotensin II, Sodium, Blood Pressure, Kidney, Kidney Function Tests, Cardiovascular System, Placebos, Celecoxib, Renin, Prostaglandins, Humans, Pyrazoles, Cardiac Output, Sodium Chloride, Dietary, Aldosterone
Abstract

1. Cyclo-oxygenase-2 (COX-2)-derived prostaglandins are important in controlling sodium excretion and renin release. In the present study, we tested the hypothesis that a clinical dose of celecoxib would impair urinary sodium excretion and elevate blood pressure (BP) during dietary salt loading. 2. Twelve normotensive individuals (mean (± SEM) age 35 ± 2 years) completed two separate 17 day dietary perturbations, one taking 200 mg/day celecoxib (CX2) and the other taking placebo (PL), randomized with a 1 month wash out. The controlled 17 day diet consisted of a 3 day run-in diet, 7 days of a low-salt (LS, 20 mmol sodium/day) diet and 7 days of a high-salt diet (HS, 350 mmol sodium/day) diet. The order in which the diets were applied was randomized. Data were collected on the last day of the LS and HS diets. 3. Plasma and urinary prostaglandins were modestly lower during celecoxib (P0.05). Urinary sodium excretion was greater (P0.01) during the HS diet (253 ± 10 vs 281 ± 27 mmol/24 h for PL vs CX2, respectively) compared with the LS diet (14 ± 3 vs 17 ± 7 mmol/24 h for PL vs CX2, respectively; P(drug) = 0.26). Celecoxib did not alter creatinine clearance (P0.50). Twenty-four hour mean arterial BP was similar during PL (87 ± 2 vs 87 ± 2 mmHg for LS and HS, respectively) and CX2 (88 ± 2 vs 87 ± 2 mmHg for LS and HS, respectively; P = 0.85), with no effect of dietary salt (P0.80). Plasma renin activity, angiotensin II and aldosterone were all suppressed with dietary salt loading (P0.05), with no effect of drug (P0.35). 4. In conclusion, blood pressure and renal function were not adversely affected by celecoxib, even during dietary salt loading. These findings support current guidelines suggesting minimal cardiovascular risks associated with short-term, low-dose use of celecoxib in young to middle-aged adults.

Published
2011

10. An evaluation of serum troponin T and signal-averaged electrocardiography in predicting electrocardiographic abnormalities after blunt chest trauma

Author

Dalva Hailstone, Frederick Giberson, Gerard J. Fulda, Amy Law, and Michael Stillabower

Subjects
Thorax, Adult, Male, medicine.medical_specialty, Thoracic Injuries, Wounds, Nonpenetrating, Sensitivity and Specificity, law.invention, Electrocardiography, Troponin T, law, Predictive Value of Tests, Internal medicine, medicine, Humans, cardiovascular diseases, Prospective Studies, Creatine Kinase, Analysis of Variance, medicine.diagnostic_test, biology, business.industry, Trauma center, Arrhythmias, Cardiac, Signal Processing, Computer-Assisted, Emergency department, Intensive care unit, Troponin, Surgery, Isoenzymes, Logistic Models, Cardiology, biology.protein, Creatine kinase, Female, business
Abstract

Objective: Despite multiple inquiries, there are no available tests to definitively detect blunt myocardial injury. The evaluation of patients with chest wall injuries without other indications for intensive care unit (ICU) admission has ranged from a single emergency department electrocardiogram (ECG) to 72 hours of continuous electrocardiographic monitoring. Recently, signal-averaged ECG and serum cardiac troponin T have demonstrated clinical utility in the evaluation of ischemic heart disease. The purpose of this study is to determine the ability of these diagnostic tests to predict the occurrence of significant electrocardiographic rhythm disturbances for patients with chest wall injuries and no other indication for ICU admission. Methods: We prospectively evaluated 71 consecutive adult patients admitted to a regional Level I trauma center with chest wall injuries not requiring ICU admission. We obtained admission signal-averaged ECG, serum troponin T level, standard ECG, and creatine phosphokinase (CPK-MB) level. Patients received continuous electrocardiographic monitoring, follow-up 12-lead electrocardiography, and serial monitoring of troponin and CPK-MB. Echocardiography was performed for patients with ahnormal CPK-MB levels. Electrocardiographic events were graded as normal, abnormal but clinically insignificant, or clinically significant. Multiple stepwise logistic regression analysis was used to evaluate predictors for the development of clinically significant electrocardiographic events. Results: On admission, 17 of 71 patients (23.9%) had normal sinus rhythm; 13 (18.3%) had a clinically significant finding. For 50 patients, follow-up ECG was abnormal; for 26, the findings were clinically significant. Of 17 patients with normal initial ECGs, 7 (41%) developed a clinically significant abnormality. Six patients received intervention for ECG findings. Eleven of 71 patients (16%) had positive troponin T; 5 of 71 (7%) had positive CPK-MB; 15 of 71 (21%) had positive signal-averaged ECG; and 4 of 13 had positive echocardiograms. Initial electrocardiographic abnormalities and a troponin T level > 0.20 μg/L were the only variables found to predict clinically significant electrocardiographic events. Sensitivity and specificity of troponin T in predicting clinically significant abnormalities were 27 and 91%, respectively. Conclusions: 1. The best predictors for the development of significant electrocardiographic changes are an admission ECG abnormality and an elevated serum troponin T level. 2. Both tests have high specificity with low to moderate sensitivity. 3. Patients with normal ECGs may develop clinically significant events. 4. CPK-MB and echocardiograms continue to be poor predictors of significant electrocardiographic events.

Published
1997

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