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2. Mineralocorticoid Receptor Antagonism by Eplerenone and Arterial Inflammation in HIV: The MIRABELLA HIV Study

Author

Srinivasa, Suman, Abohashem, Shady, Walpert, Allie R., Dunderdale, Carolyn N., Iyengar, Sanjna, Shen, Grace, Jerosch-Herold, Michael, deFilippi, Christopher R., Robbins, Gregory K., Lee, Hang, Kwong, Raymond Y., Adler, Gail K., Tawakol, Ahmed, and Grinspoon, Steven K.

Abstract

IMPORTANCE: The risk for atherosclerotic disease is increased 1.5- to 2.0-fold among persons with HIV (PWH). Increased activation of the renin-angiotensin-aldosterone system may contribute to increased arterial inflammation in this population. OBJECTIVE: To determine the effects of eplerenone on arterial inflammation among well-treated PWH without known cardiovascular disease (CVD). DESIGN, SETTING, AND PARTICIPANTS: Well-treated PWH who participated in the double-blinded, placebo-controlled, Mineralocorticoid Receptor Antagonism for Cardiovascular Health in HIV (MIRACLE HIV) study between February 2017 and March 2022 assessing the effects of eplerenone on myocardial perfusion were invited to participate in the Mineralocorticoid Receptor Antagonism By Eplerenone to Lower Arterial Inflammation in HIV (MIRABELLA) substudy if there was no current statin use. Participants were enrolled in the MIRABELLA study and underwent additional 18F-fludeoxyglucose–positron emission tomography/computed tomography (18F-FDG PET/CT) imaging of the aorta and carotid arteries to assess arterial inflammation over 12 months of treatment with eplerenone vs placebo. INTERVENTIONS: Eplerenone, 50 mg, twice a day vs identical placebo. MAIN OUTCOMES AND MEASURES: The primary outcome was change in target to background ratio (TBR), a measure of arterial wall inflammation, in the index vessel after 12 months of treatment. The index vessel was defined as the vessel (aorta, left carotid artery, or right carotid artery) with the highest TBR at baseline in each participant. RESULTS: A total of 26 participants (mean [SD] age, 54 [7] years; 18 male [69%]) were enrolled in the study. Treatment groups (eplerenone, 13 vs placebo, 13) were of similar age, sex, and body mass index. Eplerenone was associated with a reduction in TBR of the primary end point, the index vessel (eplerenone vs placebo: model treatment effect, −0.31; 95% CI, −0.50 to −0.11; P = .006; percentage change, −12.4% [IQR, −21.9% to −2.6%] vs 5.1% [IQR, −1.6% to 11.0%]; P = .003). We further observed a significant reduction of the TBR of the most diseased segment (MDS) of the index vessel (eplerenone vs placebo: −19.1% [IQR, −27.0% to −11.9%] vs 6.8% [IQR, −9.1% to 12.1%]; P = .007). A similar result was seen assessing the index vessel of the carotids (eplerenone vs placebo: −10.0% [IQR, −21.8% to 3.6%] vs 9.7% [IQR, −9.8% to 15.9%]; P = .046). Reduction in the TBR of MDS of the index vessel on 18F-FDG PET/CT correlated with improvement in the stress myocardial blood flow on cardiac magnetic resonance imaging (Spearman ρ = −0.67; P = .01). CONCLUSION AND RELEVANCE: In this small randomized clinical trial, eplerenone was associated with reduction in arterial inflammation among well-treated PWH without known CVD. In addition, reductions in arterial inflammation as measured by 18F-FDG PET/CT were related to improvements in stress myocardial perfusion. Further larger studies should explore whether eplerenone is a potential treatment strategy for inflammatory-mediated CVD in PWH. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02740179

Published
2024
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3. Survival After Invasive or Conservative Management of Stable Coronary Disease

Author

Hochman, Judith S., Anthopolos, Rebecca, Reynolds, Harmony R., Bangalore, Sripal, Xu, Yifan, O’Brien, Sean M., Mavromichalis, Stavroula, Chang, Michelle, Contreras, Aira, Rosenberg, Yves, Kirby, Ruth, Bhargava, Balram, Senior, Roxy, Banfield, Ann, Goodman, Shaun G., Lopes, Renato D., Pracoń, Radosław, López-Sendón, José, Maggioni, Aldo Pietro, Newman, Jonathan D., Berger, Jeffrey S., Sidhu, Mandeep S., White, Harvey D., Troxel, Andrea B., Harrington, Robert A., Boden, William E., Stone, Gregg W., Mark, Daniel B., Spertus, John A., Maron, David J., Hochman, Judith S., Maron, David J., Reynolds, Harmony R., Bangalore, Sripal, Mavromichalis, Stavroula, Chang, Michelle, Contreras, Aira, Esquenazi-Karonika, Shari, Gilsenan, Margaret, Gwiszcz, Ewelina, Mathews, Patenne, Mohamed, Samaa, Naumova, Anna, Roberts, Arline, VanLoo, Kerrie, Anthopolos, Rebecca, Xu, Yifan, Troxel, Andrea B., Lu, Ying, Huang, Zhen, Broderick, Samuel, Guzmán, Luis, Selvanayagam, Joseph, Lopes, Renato D., Goodman, Shaun G., Steg, Gabriel, Juliard, Jean-Michel, Doerr, Rolf, Keltai, Matyas, Bhargava, Balram, Thomas, Boban, Sharir, Tali, Nikolsky, Eugenia, Maggioni, Aldo P., Kohsaka, Shun, Escobedo, Jorge, White, Harvey D., Pracoń, Radosław, Bockeria, Olga, López-Sendón, José, Held, Claes, Senior, Roxy, Banfield, Ann, Shaw, Leslee J., Phillips, Lawrence, Berman, Daniel, Kwong, Raymond Y., Picard, Michael H., Chaitman, Bernard R., Ali, Ziad, Min, James, Mancini, G.B. John, Leipsic, Jonathon, Guzmán, Luis, Hillis, Graham, Thambar, Suku, Joseph, Majo, Selvanayagam, Joseph, Beltrame, John, Lang, Irene, Schuchlenz, Herwig, Huber, Kurt, Goetschalckx, Kaatje, Hueb, Whady, Caramori, Paulo Ricardo, de Quadros, Alexandre, Smanio, Paola, Mesquita, Claudio, Lopes, Renato D., Vitola, João, Marin-Neto, José, da Silva, Expedito Ribeiro, Tumelero, Rogério, Andrade, Marianna, Alves, Alvaro Rabelo, Dall’Orto, Frederico, Polanczyk, Carisi, Figueiredo, Estevão, Howarth, Andrew, Gosselin, Gilbert, Cheema, Asim, Bainey, Kevin, Phaneuf, Denis, Diaz, Ariel, Garg, Pallav, Mehta, Shamir, Wong, Graham, Lam, Andy, Cha, James, Galiwango, Paul, Uxa, Amar, Chow, Benjamin (Ben), Hameed, Adnan, Udell, Jacob, Cheema, Asim, Hamid, Magdy, Hauguel-Moreau, Marie, Furber, Alain, Goube, Pascal, Steg, Philippe-Gabriel, Barone-Rochette, Gilles, Thuaire, Christophe, Slama, Michel, Doerr, Rolf, Nickenig, Georg, Bekeredjian, Raffi, Schulze, P. Christian, Merkely, Bela, Fontos, Geza, Vértes, András, Varga, Albert, Bhargava, Balram, Kumar, Ajit, Nair, Rajesh G., Grant, Purvez, Manjunath, Cholenahally, Moorthy, Nagaraja, Satheesh, Santhosh, Nath, Ranjit Kumar, Wander, Gurpreet, Christopher, Johann, Dwivedi, Sudhanshu, Oomman, Abraham, Mathur, Atul, Gadkari, Milind, Naik, Sudhir, Punnoose, Eapen, Kachru, Ranjan, Christopher, Johann, Kaul, Upendra, Sharir, Tali, Kerner, Arthur, Tarantini, Giuseppe, Perna, Gian Piero, Racca, Emanuela, Mortara, Andrea, Monti, Lorenzo, Briguori, Carlo, Leone, Gianpiero, Amati, Roberto, Salvatori, Mauro, Di Chiara, Antonio, Calabro, Paolo, Galvani, Marcello, Provasoli, Stefano, Fukuda, Keiichi, Kohsaka, Shun, Nakano, Shintaro, Laucevicius, Aleksandras, Kedev, Sasko, Khairuddin, Ahmad, Escobedo, Jorge, Riezebos, Robert, Timmer, Jorik, Heald, Spencer, Stewart, Ralph, Ramos, Walter Mogrovejo, Demkow, Marcin, Mazurek, Tomasz, Drozdz, Jarozlaw, Szwed, Hanna, Witkowski, Adam, Ferreira, Nuno, Pinto, Fausto, Ramos, Ruben, Popescu, Bogdan, Pop, Calin, Bockeria, Leo, Bockeria, Olga, Demchenko, Elena, Romanov, Alexander, Bershtein, Leonid, Jizeeri, Ahmed, Stankovic, Goran, Apostolovic, Svetlana, Adjic, Nada Cemerlic, Zdravkovic, Marija, Beleslin, Branko, Dekleva, Milica, Davidovic, Goran, Chua, Terrance, Foo, David, Poh, Kian Keong, Ntsekhe, Mpiko, Sionis, Alessandro, Marin, Francisco, Miró, Vicente, López-Sendón, José, Blancas, Montserrat Gracida, González-Juanatey, José, Fernández-Avilés, Francisco, Peteiro, Jesús, Luena, Jose Enrique Castillo, Held, Claes, Aspberg, Johannes, Rossi, Mariagrazia, Kuanprasert, Srun, Yamwong, Sukit, Johnston, Nicola, Donnelly, Patrick, Moriarty, Andrew, Senior, Roxy, Elghamaz, Ahmed, Gurunathan, Sothinathan, Karogiannis, Nikolaos, Shah, Benoy N., Trimlett, Richard H.J., Rubens, Michael B., Nicol, Edward D., Mittal, Tarun K., Hampson, Reinette, Gamma, Reto, De Belder, Mark, Nageh, Thuraia, Lindsay, Steven, Mavromatis, Kreton, Miller, Todd, Banerjee, Subhash, Reynolds, Harmony, Nour, Khaled, and Stone, Peter

Published
2023
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4. Factors Associated With Coronary Angiography Performed Within 6 Months of Randomization to the Conservative Strategy in the ISCHEMIA Trial

Author

Pracoń, Radosław, Spertus, John A., Broderick, Samuel, Bangalore, Sripal, Rockhold, Frank W., Ruzyllo, Witold, Demchenko, Elena, Nageh, Thuraia, Grossman, Gabriel Blacher, Mavromatis, Kreton, Manjunath, Cholenahally N., Smanio, Paola E.P., Stone, Gregg W., Mancini, G.B. John, Boden, William E., Newman, Jonathan D., Reynolds, Harmony R., Hochman, Judith S., Maron, David J., Doan, John, Linefsky, Jason, Lee, Raven, Patel, Risha, Miller, Todd, Yang Cho, So, Milbrandt, Susan, Shelstad, Dawn, Banerjee, Subhash, Kamath, Preeti, Tejani, Ishita, Cobos, Stanley E., Quiles, Kirsten J., Dwyer, Raven R., Donnino, Robert M., Espinosa, Dalisa, Phillips, Lawrence M., Saric, Muhamed, Abdul-Nour, Khaled, Schley, Allison, Golden, Heather, Stone, Peter H., Osseni, Hermine, Wiyarand, Charlene, Douglass, Peter, Pomeroy, Hayley, Craft, Alexandra, Harvey, Bethany, Jang, James J., Anaya, Olivia, Yee, Gennie, Goold, Phoebe, Weitz, Steven, Giovannone, Steven, Pritchard, Lori, Arnold, Suzanne, Gans, Rosann, Henry O’Keefe, James, Jr, Kennedy, Paul, Shapiro, Michael D., Ganesan, Shobana, Schlichting, David, Naher, Aynun, El-Hajjar, Mohammad, Sidhu, Mandeep S., Fein, Steven A., Stewart, Wendy L., Torosoff, Mikhail T., Salmi, Kristin M., Lyubarova, Radmila, Mookherjee, Sulagna, Drzymalski, Krzysztof, McFalls, Edward O., Garcia, Santiago A., Bertog, Stefan C., Johnson, Debra K., Siddiqui, Rizwan A., Herrmann, Rebekah R., Ishani, Areef, Hansen, Ronnell A., Georges Khouri, Michel, Arges, Kristine, LeFevre, Melissa, Tomfohr, Jennifer, Goldberg, Jonathan L., Ann Byrne, Kimberly, Zappernick, Taissa, Goldweit, Richard, Canada, Sallie, Kakade, Meghana, Mieses, Patricia, Cobos, Stanley E., Dwyer, Raven R., Cohen, Ronny A., Espinosa, Dalisa, Mirrer, Brooks, Quiles, Kirsten J., Navarro, Victor, Rantinella, Magdalena, Rodriguez, Jessica, Mancilla, Olivia, Winchester, David E., Stinson, Susan, Kronenberg, Marvin, Weyand, Terry, Rogal, Philip, Crook, Sherron C., McFarren, Christopher, Heitner, John F., Ho, Jean, Khan, Saadat, Mohamed, Mahmoud, Dauber, Ira M., Soltau, Mary R., Rose, Delsa K., Wimmer, Rebecca J., Siegel, Kathy E., Derbyshire, Susan, Cannan, Charles, Dixon, Michelle, Leonard, Gerald, Sudarshan, Sriram, Heard, Ciarra, Gabriel, Viviana, Desire, Sukie, Mehta, Puja K., McDaniel, Michael, Rashid, Fauzia, Lerakis, Stamatios, Asier, Senait, Quyyumi, Arshed, Patel, Keyur, Wenger, Nanette K., Hedgepeth, Chester M., Gillis, Jennifer, Hurlburt, Heather, Manocchia, Megan, Rosen, Alan, Moore, Susan, Congdon, Elizabeth, Sahul, Zakir, Brandt, Gail, Marchelletta, Nora, Wippler, Kristina, Booth, David, Taul, Yvonne, Leung, Steve, Isaacs, Jennifer, Abdel-Latif, Ahmed, Bulkley, Viktoria, Reda, Hassan, Rodgers, Caroline, Ziada, Khaled, Setty, Sampoornima, Halverson, Kimberly E., Roraff, Christine, Thorsen, Jonean, Barua, Rajat S., Ojajuni, Amarachi, Olurinde, Oni, Surineni, Kamalakar, Hage, Fadi, Valaiyapathi, Badhma, Caldeira, Christiano, Davies, James E., Leesar, Massoud, Heo, Jaekyeong, Iskandrian, Amy, Al Solaiman, Firas, Singh, Satinder, Dajani, Khaled, Kartje, Carol M., El-Hajjar, Mohammad, Mesropian, Paul Der, Sacco, Joseph, Rawlins, Michele, McCandless, Brian, Thomson, Jennifer, Orgera, Marisa, Sidhu, Mandeep S., Colleen Rogge, Mary, Arif, Imran, Bunke, Julie, Kerr, Hanan, Unterbrink, Kendra, Fannon, Jacqueline, Burman, Cynthia, Trejo, Jorge F., Dubin, Marcia F., Fletcher, Gerald, Lane, Gary E., Neeson, Lynn M., Parikh, Pragnesh P., Pollak, Peter M., Shapiro, Brian P., Landolfo, Kevin, Gemignani, Anthony, Beaudry, Sarah, O’Rourke, Daniel, Meadows, Judith L., Tirado, Stephanie A., Halliday, Janet, Julian, Pamela, Call, Jason T., Stephanie, Lane, M., Stanford, Jennifer L., Hannan, Joseph, Bojar, Robert, Arsenault, Patricia, Kumar, Deepti, Sigel, Pamela, Mukai, John, Martin, Edward T., Brooks, Miriam, Vorobiof, Gabriel, Douangvila, Ladda, Gevorgyan, Rubine, Moorman, Alec, Ranjbaran, Fatima, Smith, Bryn, Ohmart, Carly, Kinlay, Scott, Hamburger, Robert J., Rocco, Thomas P., Ly, Samantha, Bhatt, Deepak L., Quinn, Margot C., Croce, Kevin, Temiyasathit, Sara, Quin, Jacquelyn A, Do, Jacquelyn, Anumpa, Jati, Tobin, Desiree, Zenati, Marco, Faxon, David P, Rayos, Glenn, Langdon, Jennifer, Werner Bayer, Marcia, Seedhom, Ashraf, O’Malley, Amanda, Sullenberger, Lance, Orvis, Erin, Kumkumian, Gregory, Murphy, Mandy, Greenberg, Ann, Iraola, Margaret, Sedlis, Steven P., Maranan, Leandro C., Donnino, Robert M., Lorin, Jeffrey, Tamis-Holland, Jacqueline E., Malinay, Ammy, Kornberg, Robert, Leber, Robert, Saba, Souheil, Edillo, Candice P., Lee, Michael W., Small, Delano R., Nona, Wassim, Alexander, Patrick B., Rehman, Iram, Badami, Umesh, Ostrander, Ann, Wasmiller, Stephanie, Marzo, Kevin, Drewes, Wendy, Patel, Dipti, Robbins, Inga H., Levite, Howard A., White, Jackie M, Shetty, Sanjay, Hallam, Alison, Patel, Mayuri, Hamroff, Glenn S., Spooner, Benjamin J, Hollenweger, Linda M, Little, Raymond W., Little, Holly, Zimbelman, Brandi D., Little, Tiffany, Lui, Charles Y., Eskelson, Nona A, Smith, Brigham R., Vezina, Daniel P., Khor, Lillian L., Abraham, Josephine D., Bull, David A., McKellar, Stephen H., Booth, David, Taul, Yvonne, Kotter, John, Rodgers, Caroline, Abdel-Latif, Ahmed, Isaacs, Jennifer, Bulkley, Viktoria, Hu, Bob, Kaneshiro, Renee, Labovitz, Arthur J., Berlowitz, Michael, Kirby, Bonnie J., Rogal, Philip, Tran, Nhi N., McFarren, Christopher, Jahrsdorfer, Catherine, Matar, Fadi, Caldeira, Christiano, Rodriguez, Fatima, Yunis, Reem, Schnittger, Ingela, Patro, Jhina, Fearon, William F., Deedwania, Prakash, Vega, Antonia, Reddy, Kiran, Sweeny, Joseph, Bloise-Adames, Hugo, Jimenez, Santa, Saint Vrestil, Nicole, Bhandari, Reyna, Spizzieri, Christopher, Schade, Danielle, Yost, Roxanne, Hochberg, Claudia P, Beardsley, Paula, Fine, Denise, Salerno, William D., Tancredi, Jana, Arakelian, Patricia, Mathus, Susan, O’Neill, Deborah, Wyman, Ray, Burkhardt, Joy, Hosino, Suellen, Lubyanaya, Oksana A., Salas, Jose D., Zarka, Amer, Aguirre, Maria, Shah, Anil V., Dhawan, Manu, Parra, Diana, Tran, Tri, Haldis, Thomas, Weick, Catherine, Fowler-Lehman, Katie, Spitzer, Natalie, Riedberger, Casey, Weick, Catherine, Kohn, Jeffrey A., Cobos, Stanley E., Dwyer, Raven R., Espinosa, Dalisa, Quiles, Kirsten J., Girotra, Saket, Drum, Carrie, Miller-Cox, Kimberly, Ollinger, Amy, Almousalli, Omar, Capasso-Gulve, Elizabeth, Melanie Loehr, Alaine, Mosley, Marlowe, Krishnam, Mayil S., Heydari, Shirin, Milliken, Jeffrey C., Lundeen, Andrea M., Patel, Pranav M., Karanjah, Edgar, Seto, Arnold H., Marfori, Wanda C., Harley, Kevin T., Hernandez-Rangel, Eduardo, Gibson, Michael A., Singh, Pam, Allen, Byron J., Coram, Rita, Marie Webb, Anne, Fridell, Ellie, Wilson, Heidi, Thomas, Sabu, Kim, Angela, Schwartz, Ronald G, Wilmot, Patrick, Chen, Wei, El Shahawy, Mahfouz, Stevens, Ramona, Stafford, James, Black, Loriane, Abernethy, William B., Hull, Amber B., Lim, Olivia J., Tucker, Helen C., Putnam, Natasha C., Hall, Linda L., Cauthren, Tia, Tucker, Trish, Zurick, Andrew, Horton, Hollie, Orga, Jan, Meyer, Thomas M., White, Joyce R., Morford, Ronald G., Baumann, Cynthia, Rutkin, Bruce, Seeratan, Vidya, Bokhari, Sabahat, Jimenez, Magnolia, Sokol, Seth I., Schultz, Cidney, Meisner, Jay, Russo, Jeanne, Hamzeh, Ihab, Misra, Arunima, Huda, Zohra, Wall Jr., Matthew, Boan, Araceli, Lenges De Rosen, Veronica, Alam, Mahboob, Turner, Michael C., Hinton, Christine R, Mulhearn, Thomas J., Good, Arnold P., Archer, Beth A., Dionne, Julia S., Allardyce, Cheryl A., Sikora, Lindsey N., Czerniak, Jennifer H., Mull, Jennifer A., Ferguson, Elizabeth, Laube, Frances, Shammas, Nicolas W., Shammas, Gail A, Christensen, Lori, Park, Holly, Chilton, Robert, Hecht, Joan, Nguyen, Patricia K., Vo, Davis, Hirsch, James, Jezior, Matthew, Bindeman, Jody, Salkind, Sara, Espinosa, Dalisa, Desimone, Lori-Ann, Gordon, Paul C., Felix-Stern, Lina, Crain, Thomas, Gomes, Jassira, Gordon, Catherine, Stenberg, Robert, Mann, Aimee, McCreary, Theresa, Pedalino, Ronald P., Cobos, Stanley E., Dwyer, Raven R., Espinosa, Dalisa, Quiles, Kirsten J., Wiesel, Joseph, Cobos, Stanley E., Dwyer, Raven R., Espinosa, Dalisa, Quiles, Kirsten J., Juang, George J., Gopaul, Candace, Hultberg, Karen, Huk, Tauqir, Hussain, Afshan, Al-Amoodi, Mohammed, Zambrano, Yesenia, Medina Rodriguez, Sarah, Milner, Trudie, Wohns, David, Mulder, Abbey, Van Oosterhout, Stacie, Lader, Ellis W., Meyer, Martha, Mumma, Michael, Clapp, Nancy L., Barrentine, Heather, Dharmarajan, Lekshmi, Jose, Jenne M., Cobos, Stanley E., Dwyer, Raven R., Espinosa, Dalisa, Quiles, Kirsten J., Manchery, Jenne, McGarvey Jr, Joseph F.X., McKinney, Vera, Schwarz, Linda, Downes, Thomas R., Kaczkowski, Scott M., Luckasen, Gary J., Jaskowiak, Adam J., Klitch, Joel, Cheong, Benjamin, Dees, Debra, Potluri, Srinivasa, Vasquez, Precilia, Mastouri, Ronald A., Breall, Jeffery A., Hannemann, Elise L., Revtyak, George E., Mae Foltz, Judy, Bazeley, Jonathan W., Li, Dayuan, DeRosa, Emily, Jorgenson, Beth, Riestenberg-Smith, Joyce, Giedd, Kenneth, Old, Wayne, Bariciano, Rebecca, Burt, Francis, Sokhon, Kozhaya, Waldron, Jessica, Mayon, Michelle, Gopal, Deepika, Valeti, Uma S., Ann Peichel, Gretchen, Kobashigawa, Jon, Starks, Brandy, Garcia, Lucilla, Thottam, Maria, Bhargava, Balram, Anand, Anjali, Chakanalil Govindan, Sajeev, Raj, Janitha, Gopalan Nair, Rajesh, Ravindran, Reshma, Rajalekshmi, VS, Nataraj, Nandita, Moorthy, Nagaraja, Nayak, Soundarya, Mylarappa, Mahevamma, Narayanappa, Suryaprakash, Pandit, Neeraj, Bajaj, Sheromani, Kumar Nath, Ranjit, Yadav, Vandana, Mishra, Girish, Dwivedi, S.K., Tewari, Roma, Narain, V.S., Mishra, Meenakshi, Chandra, Sharad, Patel, Shivali, Singh, Suman, Wander, Gurpreet S., Tandon, Rohit, Ralhan, Sarju, Kaur, Baljeet, Aslam, Naved, Gupta, Sonika, Goyal, Abhishek, Bhargava, Balram, Suvarna, Chandini, Karthikeyan, G., Ramakrishnan, S., Seth, Sandeep, Yadav, Rakesh, Singh, Sandeep, Roy, Ambuj, Parakh, Neeraj, Kumar Verma, Sunil, Narang, Rajiv, Mishra, Sundeep, Naik, Nitish, Sharma, Gautam, Kumar Choudhary, Shiv, Patel, Chetan, Gulati, Gurpreet, Sharma, Sanjeev, Bahl, V K, Mathew, Anoop, Mannekkattukudy Kurian, Binoy, Punnoose, Eapen, Avdhoot Gadkari, Milind, Rupesh Karwa, Sheetal, Gadage, Siddharth, Kolhe, Suvarna, Umesh Pillay, Tapan, Satheesh, Santhosh, Vindhya, R. J., Jain, Peeyush, Seth, Ashok, Singh Meharwal, Zile, Mathur, Atul, Verma, Atul, Kaul, Upendra, Bhatia, Mona, Sachdeva, Ankush, Indira Devi, Thounaojam, Jungla, Nungshi, Christopher, Johann, Manjula Rani, K., Menon, Rajeev, Sowjanya Reddy, M., Kumar, Nirmal, Preethi, K., Oomman, Abraham, sidh, Rinu R, Mao, Robert, Ramakrishnan, T., Solomon, Hilda, Francis, Rajesh, Naik, Sudhir, Vamshi, Priya P., Parveen Khan, Sajeeda, Christopher, Johann, Preethi, Kotiboinna, Kumar, Nirmal, Grant, Purvez, Hande, Shweta, Sonawane, Poonam, Kachru, Ranjan, Dubey, Abhishek, Rawat, Kavita, Kumar, Ajit, Ganapathi, Sanjay, K, Jayakumar, CP, Vineeth, Sivadasanpillai, Harikrishnan, Chacko, Manas, Sasidharan, Bijulal, Babu, Suresh, TR, Kapilamoorthy, Christopher, Johann, Reddy, Sowjanya, Polamuri, Praneeth, Rani, Manjula, Kaul, Upendra, Arambam, Priyadarshani, Singh, Bebek, Senior, Roxy, Fox, Keith AA, Young, Grace M., Carruthers, Kathryn, Senior, Roxy, Elghamaz, Ahmed, Gurunathan, Sothinathan, Karogiannis, Nikolaos, Young, Grace M., Shah, Benoy N, Kinsey, Christopher, Trimlett, Richard HJ, Kavalakkat, Raisa, Rubens, Michael B, Evans, Jo, Nicol, Edward D, Hassan, Ikraam, Mittal, Tarun K, Hampson, Reinette, Andreas Gamma, Reto, Williams, Sarah, Holland, Kim, Swan, Karen, de Belder, Mark A, Atkinson, Bev, Thambyrajah, Jeet, Kunhunny, Swapna, Davies, John R, Lindsay, Steven J., Atkinson, Craig, Kurian, John, Krannila, Carita, Jamil, Haqeel, Vinod, Manitha, Raheem, Osama, Hoye, Angela, Chaytor, Lisa, Cox, Leanne, Morrow, Julie, Rowe, Kay, Donnelly, Patrick, Kelly, Stephanie, Valecka, Bernardas, Regan, Susan, Turnbull, Dawn, Chauhan, Anoop, Fleming, Catherine, Ghosh, Arijit, Gratrix, Karen, Preston, Stephen, Barr, Craig, Cartwright, Anne, Alfakih, Khaled, Knighton, Abigail, Byrne, Jonathan, Martin, Katherine, Webb, Ian, Henriksen, Peter, Flint, Laura, Harrison, James, OKane, Peter, Lakeman, Nicki, Ljubez, Anja, de Silva, Ramesh, Conway, Dwayne S. G., Wright, Judith, Exley, Donna, Sirker, Alexander A, Andiapen, Mervyn, Richards, Amy J., Hoole, Stephen P, Wong, Lisa, Witherow, Fraser N., Munro, Melanie J., Johnston, Nicola, Harbinson, Mark, McEvoy, Michelle, Walsh, Simon, Brown, Caroline, Douglas, Hanna, Luckie, Matthew, Charles, Thabitha, Kolakaluri, Laurel, Phillips, Hannah, Sobolewska, Jolanta, Morby, Louise, Hallett, Karen, Corbett, Carolyn, Winstanley, Lynne, Jeetley, Paramjit, Smit, Angelique, Patel, Niket, Kotecha, Tushar, Travill, Christopher, Gent, Susan, Karimullah, Iqbal, Hussain, Nafisa, Al-Bustami, Mahmud, Braganza, Denise, Haines, Fiona, Taaffe, Joanne, Henderson, Robert, Burton, Jane, Pointon, Kate, Colton, Maria, Naik, Surendra, King, Rachel, Mathew, Thomas, Brown, Ammani, Docherty, Andrew, Berry, Colin, McCloy, Lisa, Collison, Damien, Robb, Kate, Roditi, Giles, Paterson, Craig, Crawford, Wenda, Kelly, Joanne, McGregor, Lorraine, Moriarty, Andrew J, Mackin, Anne, Glover, Jason D., Knight, Janet P, Pradhan, Jiwan, Mikhail, Ghada, Bose, Tuhina, Francis, Darrel P., Dzavik, Vladimir, Goodman, Shaun, Gosselin, Gilbert, Gosselin, Gilbert, Proietti, Anna, Brousseau, Myriam, Corfias, Magalie, Blaise, Patricia, Harvey, Luc, Diaz, Ariel, Rheault, Philippe, Barrero, Miguel, Gagné, Carl-Éric, Alarie, Patricia, Pépin-Dubois, Yanek, Arcand, Linda, Costa, Ricardo, Roy, Isabelle, Tung Sia, Ying, Montpetit, Estelle, Lemay, Catherine, Gisbert, Alejandro, Gervais, Pierre, Rheault, Alain, Drouin, Katia, Carl Phaneuf, Denis, Bergeron, Christine, Gosselin, Gilbert, Shelley, Christine, Masson, Christine, Garg, Pallav, Carr, Sandy, Bone, Catherine, Chow, Benjamin J.W., Moga, Ermina, Hessian, Renee C., Kourzenkova, Janetta, Beanlands, Rob S., Walter, Olga, Davies, Richard F., Bainey, Kevin R., Hogg, Norma, Welsh, Suzanne, Cheema, Asim N., Bagai, Akshay, Wald, Ron, Goodman, Shaun, Kushniriuk, Khrystyna, Joseph Graham, John, Hussain, Mohammed, Peterson, Mark, Bello, Olugbenga, Chow, Chi-Ming, Abramson, Beth, Nazir Cheema, Asim, Syed, Ishba, Hussain, Mohammed, Kushniriuk, Khrystyna, Cha, James, Otis, Judy, Otis, Rebecca, Howarth, Andrew G, Seib, Michelle M, Rivest, Sandra M, Sandonato, Rosa, Wong, Graham, Chow, Jackie, Starovoytov, Andrew, Uchida, Naomi, Meadows, Ngaire, Uxa, Amar, Asif, Nadia, Tavares, Suzana, Galiwango, Paul, Bozek, Bev, Kassam, Saleem, Shier, Maria, Mukherjee, Ashok, Larmand, Lori-Ann, Ricci, A. Joseph, Janmohamed, Amir, Hart, Brenda, Lam, Andy, Marucci, Jane, Tai, Sharon, Mehta, Shamir, Brons, Sonya, Beck, Chris, Wong, Glenda, Etherington, Krystal, Arumairajah, Thippeekaa, Udell, Jacob, Aprile, Maria, Karlsson, Sara, Webber, Susan, Généreux, Philippe, Mercure, Chantale, Hameed, Adnan, Aedy, Nancy, Daba, Ledjalem, Farquharson, Fran, Siddiqui, Anam, Carlos Carvalho, Antonio, Lopes, Renato D., Hueb, Whady, Emy Takiuti, Myrthes, Cury Rezende, Paulo, Eustáquio Ribeiro Silva, Expedito, Ciappina Hueb, Alexandre, Pizzol Caetano, Leonardo, Schaan de Quadros, Alexandre, Abdala Karam Kalil, Renato, Peixoto Deiro, Aline, Luiz da Costa Vieira, José, Manica Muller, Alice, Antonieta Pereira de Moraes, Maria, Píccaro de Oliveira, Pedro, Maria Ascoli, Bruna, Bridi, Leonardo, Zottis Poletti, Sílvia, Savaris, Simone, Vitola, João V, Cerci, Rodrigo J, Zier, Sandra S., Farias, Fabio R, Veiga Jr, Vilmar, Fernandes, Miguel M, Antonio Marin-Neto, José, Schmidt, André, de Oliveira Lima Filho, Moysés, Franca da Cunha, Diego, Mendes Oliveira, Ricardo, Reynaldo Abbud Chierice, João, Polanczyk, Carísi A., Rucatti, Guilherme G, Furtado, Mariana V., Igansi, Fernanda, Smidt, Luis F., Haeffner, Mauren P, Carlos Carvalho, Antonio, Almeida, Viviane, Pucci, Gustavo, Sanchez de Souza, Gabriela, Lyra, Flavio, Rabelo Alves Junior, Alvaro, Almeida, Mayana, dos Santos, Viviane, Dracoulakis, Marianna D. A., Oliveira, Natalia S, Lima, Rodolfo G. S. 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Marin, Valdés Chávarri, M., Quintana Giner, M., Tello Montolliu, A., Romero Aniorte, A.I., Pinar Bermudez, E., Rivera Caravaca, JM., De La Morena, G., Gracida Blancas, Montserrat, Cañavate, Olga, Guerrero, Sonia, Riera, Silvia, Enrique Castillo Luena, Jose, Enrique Castillo Luena, Jose, Lasala, Maria, Fernandez-Aviles, Francisco, Lorenzo, Maria, Sobrino, Olga, Vazquez, Alexandra, Jiang, Lixin, Chen, Jiyan, Dong, Haojian, He, Peiyu, Xia, Chunli, Yang, Junqing, Zhong, Qi, Wu, Yongjian, Tian, Yanmeng, Li, Dongze, Ma, Yitong, Li, Xiaomei, Yang, Yining, Ma, Xiang, Yu, Zixiang, Zhao, Qian, Ji, Zheng, Li, Chunguang, Zhang, Lei, Zhao, Yu, Zhu, Bolin, Yang, Xinchun, Chen, Mulei, Chi, Hongjie, Wang, Yang, Zhang, Jing, Lin, Wenhua, Jing, Rui, Liu, Jingjing, Zeng, Hesong, Zhou, Qiang, Xu, Chang, Li, Zhuxi, Li, Junhua, Xiong, Luyang, Fu, Xin, Gao, Dan, Jiang, Dengke, Leng, Ran, Wang, Xutong, Yuan, Qianqian, Zhang, Lili, Yang, Bin, Bai, Ziliang, Li, Jianhua, Qi, Jie, Wang, Fei, Wang, Haitao, Yang, Bin, Yue, Zhou, Zhang, Zhulin, Wang, Songtao, Dong, Yumei, Mao, Jiajia, Zhang, Bin, Cheng, Gong, Li, Xiuhong, Yao, Xiaowei, Zhong, Nier, Zhou, Ning, Zhao, Yulan, Huang, Yaping, Zhou, Panpan, Fang, Xuehua, Su, Wei, Zeng, Qiutang, Kunwu, Yu, Peng, Yudong, Su, Xin, Su, Xi, Wang, Chen, Zhao, Yunhai, Li, Qingxian, Geng, Yaming, Wang, Yanfu, Nie, Shao-ping, Fan, Jing-yao, Feng, Si-ting, Wang, Xiao, Yan, Yan, Zhang, Hui-min, Yu, Qin, Chi, Lingping, Liu, Fang, Wang, Jian’an, Chen, Han, Jiang, Jun, Li, Huajun, Wang, Jian’an, Han, Yechen, Xu, Lihong, Zhang, Shuyang, Liu, Zhenyu, Liu, Zhenyu, Chen, Gang, Hu, Rongrong, Maggioni, Aldo P., Piero Perna, Gian, Pietrucci, Francesca, Marini, Marco, Gabrielli, Gabriele, Provasoli, Stefano, Di Donato, Anna, Verna, Edoardo, Monti, Lorenzo, Nardi, Barbara, Di Chiara, Antonio, Pezzetta, Francesca, Mortara, Andrea, Casali, Valentina, Galvani, Marcello, Attanasio, Chiara, Ottani, Filippo, Sicuro, Marco, Leone, Gianpiero, Pisano, Francesco, Bare, Cristina, Calabro, Paolo, Fimiani, Fabio, Formisano, Tiziana, Tarantini, Giuseppe, Barioli, Alberto, Cucchini, Umberto, Ramani, Federica, Luigi Andres, Anto, Racca, Emanuela, Rolfo, Fabrizio, Goletto, Cecilia, Briguori, Carlo, De Micco, Francesca, Amati, Roberto, Di Marco, Stefano, Vergoni, William, Tricoli, Martina, Russo, Aldo, Villella, Massimo, Fanelli, Raffaele, Douglas White, Harvey, Alsweiler, Caroline, Poh, Kian-Keong, Chai, Ping, Lau, Titus, Loh, Joshua P., Tay, Edgar L., Teoh, Kristine, Tan, Sik-Yin V, Teo, Lynette L., Sia, Winnie C, Ong, Ching-Ching, Leong, Audrey W, Wong, Raymond C., Loh, Poay-Huan, Kofidis, Theodoros, Xian Chan, Wan, Hui Chan, Koo, Foo, David, Hai Yan, Li, Loh Kwok Kong, Jason, Min Er, Ching, Haider Jafary, Fahim, Chua, Terrance, Ismail, Nasrul, Tun Kyaw, Min, Yip, Deborah, Doerr, Rolf, Doerr, Rolf, Stumpf, Juergen, Grahl, Dorit, Matschke, Klaus, Guenther, Franziska, Simonis, Gregor, Bonin, Kerstin, Kadalie, Clemens T., Sechtem, Udo, Wenzelburger, Ina, Ong, Peter, Gruensfelder, Susanne, Christian Schulze, P., Goebel, Bjoern, Lenk, Karsten, Nickenig, Georg, Sinning, Jan-Malte, Weber, Marcel, Werner, Nikos, Marthe Lang, Irene, Huber, Kurt, Schuchlenz, Herwig, Steinmaurer, Gudrun, Weikl, Stefan, Marthe Lang, Irene, Winter, Max-Paul, Andric, Tijana, Huber, Kurt, Tscharre, Maximilian, Jakl-Kotauschek, Gabriele, Wegmayr, Claudia, Jäger, Bernhard, Egger, Florian, Keltai, Matyas, Vertes, Andras, Sebo, Judit, Davidovits, Zoltan, Matics, Laszlone, Varga, Albert, Ágoston, Gergely, Fontos, Geza, Dekany, Gabor, Merkely, Bela, Bartykowszki, Andrea, Maurovich-Horvat, Pal, Kerecsen, Gabor, Jakal, Agnes, Hinic, Sasa, Djokic, Jelena, Zdravkovic, Marija, Mudrenovic, Vladan, Crnokrak, Bogdan, Beleslin, Branko D., Boskovic, Nikola N., Djordjevic-Dikic, Ana D., Petrovic, Marija T., Giga, Vojislav L., Dobric, Milan R., Stepanovic, Jelena J., Markovic, Zeljko Z., Mladenovic, Ana S., Cemerlic-Adjic, Nada, Velicki, Lazar, Kamenica, Sremska, Pupic, Ljiljana, Davidović, Goran, Simović, Stefan M., Vučić, Rada, Dekleva, Milica Nikola, Martinovic, Miroslav Stevo, Stevanovic, Gordana, Stankovic, Goran, Dobric, Milan, Apostolovic, Svetlana, Martinovic, Sonja Salinger, Stanojevic, Dragana, Escobedo, Jorge, Jesús-Pérez, Ramon de, Juarez, Benito, Baleón-Espinosa, Rubén, Campos-Santaolalla, Arturo S, Durán-Cortés, Elihú, Flores-Palacios, José M, García-Rincón, Andrés, Jiménez-Santos, Moisés, Peñafiel, Joaquín V, Ortega-Ramírez, José A, Valdespino-Estrada, Aquiles, Rosas, Erick Alexánderson, Canales Brassetti, María Fernanda, Vences Anaya, Diego Adrián, García, María Pérez, Carvajal Juarez, Isabel Estela, Rovalo, Magdalena Madero, Morales Rodríguez, Erick Donato, Selvanayagam, Joseph B., Rankin, Jamie, Murphy, Deirdre, Selvanayagam, Joseph B., Lee, Sau, Joseph, Majo X., Thomas, Prince, Thambar, Suku T., Chaplin, Melissa D, Boer, Stephanie C, Beltrame, John F., Stansborough, Jeanette K., Black, Marilyn, Hillis, Graham S., Bonner, Michelle M., Ireland, Kim F., Venn-Edmonds, Clare, Steg, Philippe-Gabriel, Abergel, Helene, Juliard, Jean-Michel, Thobois, Corine, Pasteur, C.H. Louis, Thuaire, Christophe, Tachot, Emilie, Dutoiu, Téodora, Laure, Christophe, Vassaliere, Christel, Steg, Philippe Gabriel, Abergel, Helene, Juliard, Jean-Michel, Fuentes, Axelle, Slama, Michel S., Eliahou, Ludivine, Cedex, Clamart, El Mahmoud, Rami, Dubourg, Olivier, Michaud, Pierre, Nicollet, Eric, Hadjih, Sarah, Cedex, Corbeil-Essonnes, Goube, Pascal, Brito, Patricia, Barone-Rochette, Gilles, Barone-Rochette, Gilles, Furber, Alain, Cornet, Charles, Bière, Loïc, Rautureau, Jeremy, Juceviciene, Agne, Kalibataite-Rutkauskiene, Irma, Keinaite, Laura, Laucevicius, Aleksandras, Laukyte, Monika, Celutkiene, Jelena, Mikolaitiene, Gelmina, Smigelskaite, Akvile, Tamasauskiene, Ilona, Urboniene, Agne, Kedhi, Elvin, Klinieken, Isala, Timmer, Jorik, Bouwhuis, Ilse, Hermanides, Rik, Nijmeijer, Lia, Kaplan, Eliza, Riezebos, Robert K., Samadi, Pouneh, Jeannette, Schoep, J. M., Dongen, Elise van, Elisabeth, Janzen, M., Niehe, Sander R., Suryapranata, Harry, Ahoud, Sandra, Vugt, Stijn van, Ramos, Ruben, Santa Marta, Hospital de, Cacela, Duarte, Santana, Ana, Fiarresga, Antonio, Sousa, Lidia, Marques, Hugo, Patricio, Lino, Selas, Mafalda, Bernanrdes, Luis, Silva, Filipa, Rio, Pedro, Freixo, Cláudia, Carvalho, Ramiro, Ferreira, Rui, Silva, Tiago, Rodrigues, Ines, Modas, Pedro, Portugal, Guilherme, Fragata, Jose, Pinto, Fausto J., Cabrita, Inês Zimbarra, Menezes, Miguel Nobre, Rocha, Andreia, Lopes, Guilhermina Cantinho, Figueiras, Francisca Patuleia, Almeida, Ana Gomes, Coelho, Andreia, CanVas Silva, Pedro, Capinha, Marta, Nobre, Angelo, Caetano, Maria Inês, Francisco, Ana Rita, Silva, Susana, Ferreira, Nuno, de Gaia, Vila Nova, Lopes, Ricardo L., Diaz, Rafael, Guzman, Luis, Tinnirello, Veronica, Figal, Julio César, Nicolás Mungo, Matías, Buenos Aires, Ciudad Autonoma de, Méndiz, Oscar, Cortés, Claudia, Favaloro, Roberto René, Alvarez, Carlos, Garcia, Marina, Blanca, Bahia, Courtis, Javier, Godoy, Valeria, Zeballos, Gabriela, Schiavi, Lilia, Actis, Maria Victoria, Rubio, Mariano, Scaro, Graciela, White, Harvey Douglas, Alsweiler, Caroline, Devlin, Gerard Patrick, Low, Liz, Fisher, Raewyn, Scales, Jayne, Abercrombie, Kirsty, Stewart, Ralph Alan Huston, Howell, Leah, White, Harvey Douglas, Patten, Cathrine, Benatar, Jocelyne, Kedev, Sasko, Mitevska, Irena Peovska, Kostovska, Elizabeta Srbinovska, Pejkov, Hristo, Held, Claes, Held, Claes, Eggers, Kai, Frostfelt, Gunnar, Björklund, Christina, Johnston, Nina, Andreasson, Maria, Olsowka, Maciej, Essermark, Marie, Åkerblom, Axel, Soveri, Inga, Aspberg, Johannes, Persson, Liselotte, Beyar, Rafael, Sharir, Tali, Nikolsky, Eugenia, Sharir, Tali, Harel, Or, Elian, Dan, Kerner, Arthur, Bentzvi, Margalit, Massalha, Samia, Helmer, Ludmila, Kohsaka, Shun, Fukuda, Keiichi, Ueda, Ikuko, Kohsaka, Shun, Fujita, Jun, Yasuda, Satoshi, Furukawa, Akemi, Hirase, Kanae, Nagai, Toshiyuki, Otsuka, Fumiyuki, Nishimura, Shigeyuki, Nakano, Shintaro, de Werf, Frans Van, Goetschalckx, Kaatje, Goetschalckx, Kaatje, Robesyn, Valerie, de Werf, Frans Van, Claes, Kathleen, White, Harvey Douglas, Alsweiler, Caroline, Hung, Chung-Lieh, Yang, Yi-Hsuan, Yun, Chun-Ho, Hou, Charles Jia-Yin, Kuo, Jen-Yuan, Yeh, Hung-I, Hung, Ta-Chuan, Li, Jiun-Yi, Chien, Chen-Yen, Tsai, Cheng-Ting, Liu, Chun-Chieh, Yu, Fa-Chang, Lin, Yueh-Hung, Lan, Wei-Ren, Yen, Chih-Hsuan, Tsai, Jui-Peng, Sung, Kuo-Tzu, Ntsekhe, Mpiko, Pandie, Shaheen, Philander (Nee Talliard), Constance, Viljoen, Charle A, Mtana, Noloyiso, De Andrade, Marianne, Maggioni, Aldo P., Moccetti, Tiziano, Anesini, Adriana, Rossi, M.Grazia, Maspoli, Simona, Mombelli, Manuela, Abdelhamid, Magdy, Talaat, Ahmed, Adel, Ahmed, Kamal, Ahmed, Mahrous, Hossam, Kaffas, Sameh El, Fishawy, Hussien El, Pop, Calin, Claudia, Matei, Popescu, Bogdan A., Ginghina, Carmen, Rosca, Monica, Deleanu, Dan, Beladan, Carmen C., Iliescu, Vlad A., Al-Mallah, Mouaz H., Zahrani, Sarah, Aljzeeri, Ahmed, Najm, Hani, Alghamdi, Ali, Mogrovejo Ramos, Walter Enrique, Monsalve Davila, Marco Antonio, White, Harvey Douglas, Alsweiler, Caroline, Kuanprasert, Srun, Mai, Chiang, Prommintikul, Arintaya, Nawarawong, Weerachai, Khwakhong, Supatchara, Woragidpoonpol, Surin, Chaiyasri, Anong, Tepsuwan, Thitipong, Mekara, Warangkana, Taksaudom, Noppon, Kulthawong, Supap, Rimsukcharoenchai, Chataroon, Amaritakomol, Anong, Euathrongchit, Juntima, Wannasopha, Yutthaphan, Yamwong, Sukit, Panpunuan, Pachara, Sritara, Piyamitr, Aramcharoen, Suthara, Meemuk, Krissada, White, Harvey Douglas, Alsweiler, Caroline, Khairuddin, Ahmad, Mokhtar, Noor Syamira, Hadi, Hafidz Abd, Basri, Nor Asiah, Yahaya, Shaiful Azmi, Yusnida, Irni, Hashim, Humayrah, Harrington, Robert, Williams, David, Alexander, Karen P., Berger, Jeffrey, Harrington, Robert, Mark, Daniel, O’Brien, Sean M., Rosenberg, Yves, Shaw, Leslee J., Ballantyne, Christie, Berman, Daniel, Beyar, Rafael, Bhargava, Balram, Buller, Chris, (Tony) Carvalho*, Antonio, Chaitman, Bernard R., Diaz, Rafael, Doerr, Rolf, Dzavik, Vladimir, Goodman, Shaun, Gosselin, Gilbert, Hachamovitch, Rory, Hamm, Christian, Held, Claes, Helm, Malte, Huber, Kurt, Jiang, Lixin, Keltai, Matyas, Kohsaka, Shun, Lang, Irene, Lopes, Renato, Lopez-Sendon, Jose, Maggioni, Aldo, Bairey Merz, C. Noel, Min, James, Peterson, Eric, Picard, Michael H., Selvanayagam, Joseph, Senior, Roxy, Sharir, Tali, Steg, Gabriel, Szwed, Hanna, de Werf, Frans Van, Weintraub, William, White, Harvey, Williams, David, Ballantyne, Christie, Calfas*, Karen, Chaitman, Bernard R., Champagne, Mary Ann, Davidson, Michael, Fleg, Jerome, McCullough, Peter A., Stone, Peter, Menasche, Philippe, Davidson*, Michael, Fremes, Stephen, Guyton, Robert, Mack, Michael, Mohr, Fred, Rao, Anupama, Sabik, Joe, Shapira, Oz, Taggart, David, Tatoulis, James, Williams, David, Blankenship, Jim, Brener, Sorin, Buller, Chris, Colombo, Antonio, Bruyne, Bernard de, Généreux, Philippe, Harrington, Robert, Kereiakes, Dean, Lefevre, Thierry, Moses, Jeffrey, Chaitman, Bernard R., Alexander, Karen P., Mahaffey, Ken, White, Harvey, Chaitman, Bernard R., Cruz-Flores, Salvador, Danchin, Nicholas, Feen, Eli, Garcia, Mario J., Hauptman, Paul, Laddu, Abhay A., Passamani, Eugene, Pina, Ileana L., Simoons, Maarten, Skali, Hicham, Thygesen, Kristian, Waters, David, Alexander, Karen P., Endsley, Patricia, Esposito, Gerard, Kanters, Jeffrey, Pownall, John, Stournaras, Dimitrios, Shaw, Leslee J., Berman, Daniel, Friedrich, Matthias, Hachamovitch, Rory, Kwong, Raymond, Min, James, Oliver, Dana, Picard, Michael H., Harrell, Frank, Blume, Jeffrey, Lee, Kerry, O’Brien, Sean M., Berger, Jeffrey, Held, Claes, Kullo, Iftikhar, McManus, Bruce, Newby, Kristin, Mark, Daniel, Cohen, David, Weintraub, William, Merz, C. Noel Bairey, Bugiardini, Raffaele, Celutkiene, Jelena, Escobedo, Jorge, Hoye, Angela, Lyubarova, Radmila, Mattina, Deirdre, Peteiro, Jesus, Alexander, Karen P., Berger, Jeffrey, Harrington, Robert, O’Brien, Sean M., Rosenberg, Yves, Mark, Daniel, Mark, Daniel, Shaw, Leslee J., Berman, Dan, Chaitman, Bernard R., Fleg, Jerome, Kwong, Raymond, Picard, Michael H., Senior, Roxy, Min, James, Leipsic, Jonathan, Ali, Ziad, Williams, David, Fleg, Jerome, Berger, Jeffrey, Chaitman, Bernard R., Alexander, Karen P., Alexander, Karen P., Fleg, Jerome, Mathew, Roy, O’Brien, Sean M., Sidhu, Mandeep, Friedman, Lawrence, Anderson, Jeffrey, Berg, Jessica, DeMets, David, Gibson, C. Michael, Lamas, Gervasio, Deming, Nicole, Himmelfarb, Jonathan, Ouyang, Pamela, Woodard, Pamela, Harrell, Frank, Nwosu, Samuel, Rosenberg, Yves, Fleg, Jerome, Kirby, Ruth, Jeffries, Neal, Berger, Jeffrey, Sidhu, Mandeep, Denaro*, Jean E., Mavromichalis, Stephanie, Chan, Kevin, Cobb, Gia, Contreras, Aira, Cukali, Diana, Ferket, Stephanie, Gabriel, Andre, Hansen, Antonietta, Roberts, Arline, Chang, Michelle, Islam, Sharder, Wayser, Graceanne, Yakubov, Solomon, Yee, Michelle, Callison, Caroline, Hogan, Isabelle, Qelaj, Albertina, Pirro, Charlotte, Loo, Kerrie Van, Wisniewski, Brianna, Gilsenan, Margaret, Lang, Bevin, Mohamed, Samaa, Esquenazi-Karonika, Shari, Mathews, Patenne, Naumova, Anna, Lyo, Jihyun, Setang, Vincent, Xavier, Mark, O’Brien, Sean M., Alexander, Karen P., Mark, Daniel B., Anstrom, Kevin, Baloch, Khaula, Blount, Janet, Cowper, Patricia, Davidson-Ray, Linda, Drew, Laura, Harding, Tina, Knight, J David, Liu, Diane Minshall, O’Neal, Betsy, Redick, Thomas, Jones, Philip, Nugent, Karen, Wang, Grace Jingyan, Shaw, Leslee J., Phillips, Lawrence, Goyal, Abhinav, Hetrick, Holly, Oliver, Dana, Berman, Daniel, Hayes, Sean W., Friedman, John D., Gerlach, R. James, Hyun, Mark, Miranda-Peats, Romalisa, Slomka, Piotr, Thomson, Louise, Kwong, Raymond Y., Friedrich, Matthias, Mongeon, Francois Pierre, Michael, Steven, Picard, Michael H., Hung, Judy, Scherrer-Crosbie, Marielle, Zeng, Xin, Chaitman, Bernard R., Eckstein, Jane, Guruge, Bandula, Streif, Mary, Ali, Ziad, Genereux, Philippe, Alfonso, Maria A., Corral, Maria P., Garcia, Javier J., Horst, Jennifer, Jankovic, Ivana, Konigstein, Maayan, Lustre, Mitchel B., Peralta, Yolayfi, Sanchez, Raquel, Min, James, Arsanjani, Reza, Budoff, Matthew, Elmore, Kimberly, Gomez, Millie, Hague, Cameron, Hindoyan, Niree, Leipsic, Jonathan, Nakanishi, Rine, Srichai-Parsia, M. Barbara, Yeoh, Eunice, Youn, Tricia, Maggioni, Aldo P., Bianchini, Francesca, Ceseri, Martina, Lorimer, Andrea, Magnoni, Marco, Orso, Francesco, Sarti, Laura, Tricoli, Martinia, Carvalho, Antonio, Lopes, Renato, Barbosa, Lilian Mazza, Duarte, Tauane Bello, Soares, Tamara Colaiácovo, Aveiro Morata, Julia de, Carvalho, Pedro, Carvalho Maffei, Natalia de, Egydio, Flávia, Kawakami, Anelise, Oliveira, Janaina, Piloto, Elissa Restelli, Pozzibon, Jaqueline, Goodman, Shaun, Camara, Diane, Mowafy, Neamat, Spindler, Caroline, Jiang, Lixin, Dai, Hao, Feng, Fang, Li, Jia, Li, Li, Liu, Jiamin, Xie, Qiulan, Zhang, Haibo, Zhang, Jianxin, Zhang, Lihua, Zhang, Liping, Zhang, Ning, Zhong, Hui, Diaz, Rafael, Escobar, Claudia, Martin, Maria Eugenia, Pascual, Andrea, Lopez-Sendon, José, Moraga, Paloma, Hernandez, Victoria, Castro, Almudena, Posada, Maria, Fernandez, Sara, Villanueva, José Luis Narro, Selgas, Rafael, Steg, Gabriel, Abergel, Helene, Juliard, Jean Michel, White, Harvey, Alsweiler, Caroline, de Werf, Frans Van, Claes, Kathleen, Goetschalckx, Kaatje, Luyten, Ann, Robesyn, Valerie, Selvanayagam, Joseph B., Murphy, Deirdre, Ahmed, Asker, Bhatt, Richa, Chadha, Nitika, Kumar, Vijay, Lubna, Sadath, Naik, Pushpa, Pandey, Shruti, Ramasamy, Karthik, Saleem, Mohammed, Sharma, Pratiksha, and Siddaram, Hemalata

Published
2024
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6. Outcomes in the ISCHEMIA Trial Based on Coronary Artery Disease and Ischemia Severity

Author

Reynolds, Harmony R., Shaw, Leslee J., Min, James K., Page, Courtney B., Berman, Daniel S., Chaitman, Bernard R., Picard, Michael H., Kwong, Raymond Y., O’Brien, Sean M., Huang, Zhen, Mark, Daniel B., Nath, Ranjit K., Dwivedi, Sudhanshu K., Smanio, Paola E.P., Stone, Peter H., Held, Claes, Keltai, Matyas, Bangalore, Sripal, Newman, Jonathan D., Spertus, John A., Stone, Gregg W., Maron, David J., and Hochman, Judith S.

Abstract

Supplemental Digital Content is available in the text.

Published
2021
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7. Toward Replacing Late Gadolinium Enhancement With Artificial Intelligence Virtual Native Enhancement for Gadolinium-Free Cardiovascular Magnetic Resonance Tissue Characterization in Hypertrophic Cardiomyopathy

Author

Zhang, Qiang, Burrage, Matthew K., Lukaschuk, Elena, Shanmuganathan, Mayooran, Popescu, Iulia A., Nikolaidou, Chrysovalantou, Mills, Rebecca, Werys, Konrad, Hann, Evan, Barutcu, Ahmet, Polat, Suleyman D., Salerno, Michael, Jerosch-Herold, Michael, Kwong, Raymond Y., Watkins, Hugh C., Kramer, Christopher M., Neubauer, Stefan, Ferreira, Vanessa M., and Piechnik, Stefan K.

Abstract

Supplemental Digital Content is available in the text.

Published
2021
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8. Evaluation of Stress Cardiac Magnetic Resonance Imaging in Risk Reclassification of Patients With Suspected Coronary Artery Disease

Author

Antiochos, Panagiotis, Ge, Yin, Steel, Kevin, Chen, Yi-Yun, Bingham, Scott, Abdullah, Shuaib, Mikolich, J. Ronald, Arai, Andrew E., Bandettini, W. Patricia, Patel, Amit R., Farzaneh-Far, Afshin, Heitner, John F., Shenoy, Chetan, Leung, Steve W., Gonzalez, Jorge A., Shah, Dipan J., Raman, Subha V., Ferrari, Victor A., Schulz-Menger, Jeanette, Stuber, Matthias, Simonetti, Orlando P., Murthy, Venkatesh L., and Kwong, Raymond Y.

Abstract

IMPORTANCE: The role of stress cardiac magnetic resonance (CMR) imaging in clinical decision-making by reclassification of risk across American College of Cardiology/American Heart Association guideline–recommended categories has not been established. OBJECTIVE: To examine the utility of stress CMR imaging for risk reclassification in patients without a history of coronary artery disease (CAD) who presented with suspected myocardial ischemia. DESIGN, SETTING, AND PARTICIPANTS: A retrospective, multicenter cohort study with median follow-up of 5.4 years (interquartile range, 4.6-6.9) was conducted at 13 centers across 11 US states. Participants included 1698 consecutive patients aged 35 to 85 years with 2 or more coronary risk factors but no history of CAD who presented with suspected myocardial ischemia to undergo stress CMR imaging. The study was conducted from February 18, 2019, to March 1, 2020. MAIN OUTCOMES AND MEASURES: Cardiovascular (CV) death and nonfatal myocardial infarction (MI). Major adverse CV events (MACE) including CV death, nonfatal MI, hospitalization for heart failure or unstable angina, and late, unplanned coronary artery bypass graft surgery. RESULTS: Of the 1698 patients, 873 were men (51.4%); mean (SD) age was 62 (11) years, accounting for 67 CV death/nonfatal MIs and 190 MACE. Clinical models of pretest risk were constructed and patients were categorized using guideline-based categories of low (<1% per year), intermediate (1%-3% per year), and high (>3% year) risk. Stress CMR imaging provided risk reclassification across all baseline models. For CV death/nonfatal MI, adding stress CMR-assessed left ventricular ejection fraction, presence of ischemia, and late gadolinium enhancement to a model incorporating the validated CAD Consortium score, hypertension, smoking, and diabetes provided significant net reclassification improvement of 0.266 (95% CI, 0.091-0.441) and C statistic improvement of 0.086 (95% CI, 0.022-0.149). Stress CMR imaging reclassified 60.3% of patients in the intermediate pretest risk category (52.4% reclassified as low risk and 7.9% as high risk) with corresponding changes in the observed event rates of 0.6% per year for low posttest risk and 4.9% per year for high posttest risk. For MACE, stress CMR imaging further provided significant net reclassification improvement (0.361; 95% CI, 0.255-0.468) and C statistic improvement (0.092; 95% CI, 0.054-0.131), and reclassified 59.9% of patients in the intermediate pretest risk group (48.7% reclassified as low risk and 11.2% as high risk). CONCLUSIONS AND RELEVANCE: In this multicenter cohort of patients with no history of CAD presenting with suspected myocardial ischemia, stress CMR imaging reclassified patient risk across guideline-based risk categories, beyond clinical risk factors. The findings of this study support the value of stress CMR imaging for clinical decision-making, especially in patients at intermediate risk for CV death and nonfatal MI.

Published
2020
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9. Association of Sex With Severity of Coronary Artery Disease, Ischemia, and Symptom Burden in Patients With Moderate or Severe Ischemia: Secondary Analysis of the ISCHEMIA Randomized Clinical Trial

Author

Reynolds, Harmony R., Shaw, Leslee J., Min, James K., Spertus, John A., Chaitman, Bernard R., Berman, Daniel S., Picard, Michael H., Kwong, Raymond Y., Bairey-Merz, C. Noel, Cyr, Derek D., Lopes, Renato D., Lopez-Sendon, Jose Luis, Held, Claes, Szwed, Hanna, Senior, Roxy, Gosselin, Gilbert, Nair, Rajesh Gopalan, Elghamaz, Ahmed, Bockeria, Olga, Chen, Jiyan, Chernyavskiy, Alexander M., Bhargava, Balram, Newman, Jonathan D., Hinic, Sasa B., Jaroch, Joanna, Hoye, Angela, Berger, Jeffrey, Boden, William E., O’Brien, Sean M., Maron, David J., and Hochman, Judith S.

Abstract

IMPORTANCE: While many features of stable ischemic heart disease vary by sex, differences in ischemia, coronary anatomy, and symptoms by sex have not been investigated among patients with moderate or severe ischemia. The enrolled ISCHEMIA trial cohort that underwent coronary computed tomographic angiography (CCTA) was required to have obstructive coronary artery disease (CAD) for randomization. OBJECTIVE: To describe sex differences in stress testing, CCTA findings, and symptoms in ISCHEMIA trial participants. DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of the multicenter ISCHEMIA randomized clinical trial analyzed baseline characteristics of patients with stable ischemic heart disease. Individuals were enrolled from July 2012 to January 2018 based on local reading of moderate or severe ischemia on a stress test, after which blinded CCTA was performed in most. Core laboratories reviewed stress tests and CCTAs. Participants with no obstructive CAD or with left main CAD of 50% or greater were excluded. Those who met eligibility criteria including CCTA (if performed) were randomized to a routine invasive or a conservative management strategy (N = 5179). Angina was assessed using the Seattle Angina Questionnaire. Analysis began October 1, 2018. INTERVENTIONS: CCTA and angina assessment. MAIN OUTCOMES AND MEASURES: Sex differences in stress test, CCTA findings, and symptom severity. RESULTS: Of 8518 patients enrolled, 6256 (77%) were men. Women were more likely to have no obstructive CAD (<50% stenosis in all vessels on CCTA) (352 of 1022 [34.4%] vs 378 of 3353 [11.3%]). Of individuals who were randomized, women had more angina at baseline than men (median [interquartile range] Seattle Angina Questionnaire Angina Frequency score: 80 [70-100] vs 90 [70-100]). Women had less severe ischemia on stress imaging (383 of 919 [41.7%] vs 1363 of 2972 [45.9%] with severe ischemia; 386 of 919 [42.0%] vs 1215 of 2972 [40.9%] with moderate ischemia; and 150 of 919 [16.3%] vs 394 of 2972 [13.3%] with mild or no ischemia). Ischemia was similar by sex on exercise tolerance testing. Women had less extensive CAD on CCTA (205 of 568 women [36%] vs 1142 of 2418 men [47%] with 3-vessel disease; 184 of 568 women [32%] vs 754 of 2418 men [31%] with 2-vessel disease; and 178 of 568 women [31%] vs 519 of 2418 men [22%] with 1-vessel disease). Female sex was independently associated with greater angina frequency (odds ratio, 1.41; 95% CI, 1.13-1.76). CONCLUSIONS AND RELEVANCE: Women in the ISCHEMIA trial had more frequent angina, independent of less extensive CAD, and less severe ischemia than men. These findings reflect inherent sex differences in the complex relationships between angina, atherosclerosis, and ischemia that may have implications for testing and treatment of patients with suspected stable ischemic heart disease. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01471522

Published
2020
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12. ACC/AHA/ASE/ASNC/ASPC/HFSA/HRS/SCAI/SCCT/SCMR/STS 2023 Multimodality Appropriate Use Criteria for the Detection and Risk Assessment of Chronic Coronary Disease

Author

Winchester, David E., Maron, David J., Blankstein, Ron, Chang, Ian C., Kirtane, Ajay J., Kwong, Raymond Y., Pellikka, Patricia A., Prutkin, Jordan M., Russell, Raymond, and Sandhu, Alexander T.

Abstract

The American College of Cardiology (ACC) Foundation, along with key specialty and subspecialty societies, conducted an appropriate use review of stress testing and anatomic diagnostic procedures for risk assessment and evaluation of known or suspected chronic coronary disease (CCD), formerly referred to as stable ischemic heart disease (SIHD). This document reflects an updating of the prior Appropriate Use Criteria (AUC) published for radionuclide imaging, stress echocardiography (echo), calcium scoring, coronary computed tomography angiography (CCTA), stress cardiac magnetic resonance (CMR), and invasive coronary angiography for SIHD. This is in keeping with the commitment to revise and refine the AUC on a frequent basis. As with the prior version of this document, rating of test modalities is provided side-by-side for a given clinical scenario. These ratings are explicitly not considered competitive rankings due to the limited availability of comparative evidence, patient variability, and the range of capabilities available in any given local setting1–4.

Published
2023
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13. Predictive value of cardiac magnetic resonance right ventricular longitudinal strain in patients with suspected myocarditis

Author

Bernhard, Benedikt, Tanner, Giulin, Garachemani, Davide, Schnyder, Aaron, Fischer, Kady, Huber, Adrian T., Safarkhanlo, Yasaman, Stark, Anselm W., Guensch, Dominik P., Schütze, Jonathan, Greulich, Simon, Bastiaansen, Jessica A.M., Pavlicek-Bahlo, Maryam, Benz, Dominik C., Kwong, Raymond Y., and Gräni, Christoph

Abstract

Recent evidence underlined the importance of right (RV) involvement in suspected myocarditis. We aim to analyze the possible incremental prognostic value from RV global longitudinal strain (GLS) by CMR.

Published
2023
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14. Effect of Omega-3 Acid Ethyl Esters on Left Ventricular Remodeling After Acute Myocardial Infarction

Author

Heydari, Bobak, Abdullah, Shuaib, Pottala, James V., Shah, Ravi, Abbasi, Siddique, Mandry, Damien, Francis, Sanjeev A., Lumish, Heidi, Ghoshhajra, Brian B., Hoffmann, Udo, Appelbaum, Evan, Feng, Jiazhuo H., Blankstein, Ron, Steigner, Michael, McConnell, Joseph P., Harris, William, Antman, Elliott M., Jerosch-Herold, Michael, and Kwong, Raymond Y.

Abstract

Supplemental Digital Content is available in the text.

Published
2016
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15. Abstract 12499: Anomalous Coronary Arteries Are Associated With Ischemia in the Ischemia Trial

Author

Jaspan, Vita, Leipsic, Jonathon A, Nemeth, Hayley, Mancini, G B, Budoff, Matthew, Hague, Cameron, Min, James, Shaw, Leslee J, Berman, Daniel, Picard, Michael, Chaitman, Bernard R, Kwong, Raymond Y, OBrien, Sean, Hochman, Judith S, Maron, David J, and Reynolds, Harmony

Abstract

Introduction:Coronary anomalies are detected in 0.3-2.3% of patients undergoing coronary computed tomography angiography (CCTA). Data are scarce on atherosclerosis severity in anomalous arteries and relationship to ischemia on stress testing.Hypothesis:High risk features of anomalous coronary arteries are associated with ischemia, even in the absence of coronary stenosis on CCTA.Methods:5,903 participants enrolled in the ISCHEMIA trial program with site-determined moderate or severe ischemia underwent CCTA. A core laboratory assessed atherosclerosis severity and made note of anomalous coronary origin. A single reader at the CCTA core laboratory re-evaluated all identified anomalies to assess high risk features and origin, blinded to stress test results. Patients were excluded if stress test results were unavailable. We assessed the relationship between type of anomaly and vessel with ischemia in the subtended territory on stress imaging, and stenosis severity.Results:There was anomalous origin of a coronary artery in 56 of 5,903 CCTA cases (0.9%). Age, sex and CAD risk factors were similar between patients with vs. without anomalies. Anomalous origin affected the left circumflex (LCX) in 28, right coronary artery (RCA) in 21, left main (LM) in 4, and left anterior descending (LAD) in 3. Ischemia was severe on stress testing in 58.2%, moderate in 34.5%, mild in 3.6% and absent in 3.6%. High risk anomalies were present in 17/56 (30.3%, 16/21 RCA and 1/4 LM), including inter-arterial course in 28.6%, intra-mural course in 1.8%, and slit-like orifice in 12.5%. Most anomalous coronaries (82.9%) were associated with ischemia in the subtended territory. Among anomalies associated with ischemia, 37.9% had <50% stenosis and 62.1% had <70% stenosis (Figure). Of those with <70% stenosis, 27.6% had high risk features.Conclusions:Anomalous coronary arteries in stable patients are associated with ischemia, even in the absence of severe atherosclerotic disease.

Published
2022
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17. Weight loss and progressive left ventricular remodelling: The Multi-Ethnic Study of Atherosclerosis (MESA)

Author

Shah, Ravi V, Murthy, Venkatesh L, Abbasi, Siddique A, Eng, John, Wu, Colin, Ouyang, Pamela, Kwong, Raymond Y, Goldfine, Allison, Bluemke, David A, Lima, Joao, and Jerosch-Herold, Michael

Abstract

Aims Impact of weight loss on cardiac structure has not been extensively investigated in large, multi-ethnic, community-based populations. We investigated the longitudinal impact of weight loss on cardiac structure by cardiac magnetic resonance (CMR).Methods and results 2351 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) who underwent CMR at Exam 1 (2002) and Exam 5 (2011) were included. Primary outcomes were percentage change in LV mass (indexed to height) and LV mass-to-volume ratio (concentric LV remodelling). Multivariable linear regression was used to measure the association between outcomes and weight change. At median 9.4 years’ follow-up, 639 individuals (27%) experienced >5% weight loss (median 6.9 kg) and 511 (22%) had >5% weight gain (median 6.4 kg). A >5% weight gain was associated with the greatest increase in LV mass (+5.4% median) and LV mass-to-volume ratio (+12.2% median). Adjusting for medications, hypertension/diabetes (and change in these risk factors), age, race and other risk factors, every 5% weight loss was associated with a 1.3% decrease in height-indexed LV mass and 1.3% decrease in LV mass-to-volume ratio (p<0.0001). There was no effect modification/confounding by age, race, gender or baseline BMI. Change in LV mass-to-volume ratio was roughly linear, specifically for modest degrees of weight loss (−10% to +10%). Change in LV mass was linear with weight loss, suggesting no threshold of weight loss is needed for LV mass regression.Conclusions In a large multi-ethnic population, weight loss is associated with beneficial effects on cardiac structure, independent of age, race, gender, BMI and obesity-related cardiometabolic risk. There is no threshold of weight loss required to produce these effects.

Published
2015
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18. Diltiazem Treatment for Pre-Clinical Hypertrophic Cardiomyopathy Sarcomere Mutation Carriers

Author

Ho, Carolyn Y., Lakdawala, Neal K., Cirino, Allison L., Lipshultz, Steven E., Sparks, Elizabeth, Abbasi, Siddique A., Kwong, Raymond Y., Antman, Elliott M., Semsarian, Christopher, González, Arantxa, López, Begoña, Diez, Javier, Orav, E. John, Colan, Steven D., and Seidman, Christine E.

Abstract

The study sought to assess the safety, feasibility, and effect of diltiazem as disease-modifying therapy for at-risk hypertrophic cardiomyopathy (HCM) mutation carriers.

Published
2015
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19. T1 Measurements for Detection of Expansion of the Myocardial Extracellular Volume in Chronic Obstructive Pulmonary Disease

Author

Neilan, Tomas G., Bakker, Jessie P., Sharma, Bhavneesh, Owens, Robert L., Farhad, Hoshang, Shah, Ravi V., Abbasi, Siddique A., Kohli, Puja, Wilson, Joel, DeMaria, Anthony, Jerosch-Herold, Michael, Kwong, Raymond Y., and Malhotra, Atul

Abstract

We aimed to assess whether chronic obstructive pulmonary disease (COPD) is associated with expansion of the myocardial extracellular volume (ECV) using T1 measurements.

Published
2014
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21. Infarct Tissue Heterogeneity by Contrast-Enhanced Magnetic Resonance Imaging Is a Novel Predictor of Mortality in Patients With Chronic Coronary Artery Disease and Left Ventricular Dysfunction

Author

Watanabe, Eri, Abbasi, Siddique A., Heydari, Bobak, Coelho-Filho, Otavio R., Shah, Ravi, Neilan, Tomas G., Murthy, Venkatesh L., Mongeon, François-Pierre, Barbhaiya, Chirag, Jerosch-Herold, Michael, Blankstein, Ron, Hatabu, Hiroto, van der Geest, Robert J., Stevenson, William G., and Kwong, Raymond Y.

Abstract

Supplemental Digital Content is available in the text.

Published
2014
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23. Left Atrial Passive Emptying Function Determined by Cardiac Magnetic Resonance Predicts Atrial Fibrillation Recurrence After Pulmonary Vein Isolation

Author

Dodson, John A., Neilan, Tomas G., Shah, Ravi V., Farhad, Hoshang, Blankstein, Ron, Steigner, Michael, Michaud, Gregory F., John, Roy, Abbasi, Siddique A., Jerosch-Herold, Michael, and Kwong, Raymond Y.

Abstract

Although pulmonary vein isolation has become a mainstream therapy for selected patients with atrial fibrillation (AF), late recurrent AF is common and its risk factors remain poorly defined. The purpose of our study was to test the hypothesis that reduced left atrial passive emptying function (LAPEF) as determined by cardiac magnetic resonance has a strong association with late recurrent AF after pulmonary vein isolation.

Published
2014
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24. Cardiac T1Imaging

Author

Jerosch-Herold, Michael and Kwong, Raymond Y.

Abstract

T1mapping of the heart has evolved into a valuable tool to evaluate myocardial tissue properties, with or without contrast injection, including assessment of myocardial edema and free water content, extracellular volume (expansion), and most recently cardiomyocyte hypertrophy. The magnetic resonance imaging pulse sequence techniques developed for these applications have had to address at least 2 important considerations for cardiac applications: measure magnetization-inversion recoveries during cardiac motion with sufficient temporal resolution for the shortest expected T1values, and, second, obtain these measurements within a time during which a patient can comfortably suspend breathing. So-called Look-Locker techniques, and variants thereof, which all sample multiple points of a magnetization recovery after each magnetization preparation, have therefore become a mainstay in this field. The rapid pace of advances and new findings based on cardiac T1mapping for assessment of diffuse fibrosis or myocardial edema show that these techniques enrich the capabilities of magnetic resonance imaging for myocardial tissue profiling, which is arguably unmatched by other cardiac imaging modalities.

Published
2014
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25. T1 Measurements Identify Extracellular Volume Expansion in Hypertrophic Cardiomyopathy Sarcomere Mutation Carriers With and Without Left Ventricular Hypertrophy

Author

Ho, Carolyn Y., Abbasi, Siddique A., Neilan, Tomas G., Shah, Ravi V., Chen, Yucheng, Heydari, Bobak, Cirino, Allison L., Lakdawala, Neal K., Orav, E. John, González, Arantxa, López, Begoña, Díez, Javier, Jerosch-Herold, Michael, and Kwong, Raymond Y.

Abstract

Myocardial fibrosis is a hallmark of hypertrophic cardiomyopathy (HCM) and a potential substrate for arrhythmias and heart failure. Sarcomere mutations seem to induce profibrotic changes before left ventricular hypertrophy (LVH) develops. To further evaluate these processes, we used cardiac magnetic resonance with T1 measurements on a genotyped HCM population to quantify myocardial extracellular volume (ECV).

Published
2013
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26. Effect of Cardiac Stem Cells on Left-Ventricular Remodeling in a Canine Model of Chronic Myocardial Infarction

Author

Welt, Frederick G.P., Gallegos, Robert, Connell, John, Kajstura, Jan, D’Amario, Domenico, Kwong, Raymond Y., Coelho-Filho, Otavio, Shah, Ravi, Mitchell, Richard, Leri, Annarosa, Foley, Lori, Anversa, Piero, and Pfeffer, Marc A.

Abstract

Regenerative medicine, including cell therapy, is a promising strategy for recovery of the damaged myocardium. C-kit–positive cardiac stem cells (CSCs) have been shown to improve myocardial function after ischemic injury in animal models and in early clinical experience. We used a chronic large animal model of myocardial infarction with substantial reductions in left-ventricular (LV) ejection fraction and adverse remodeling to examine the effect of late autologous CSC intramyocardial injection on long-term cardiac structure and function.

Published
2013
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27. Optimal imaging strategies to assess coronary blood flow and risk for patients with coronary artery disease

Author

Jerosch-Herold, Michael and Kwong, Raymond Y

Abstract

This review is meant as a balanced summary of the current state of cardiac magnetic resonance (CMR) perfusion imaging in assessing alterations in myocardial blood flow due to coronary artery disease (CAD). We aim to provide first an accessible technical overview of first-pass CMR perfusion imaging and contrast it with other conventional perfusion imaging modalities, and then address the potential advantages of CMR for a qualitative assessment of perfusion defects, as well as quantitative blood flow measurements. Most recent results from clinical trials on the utility of CMR perfusion and novel directions will be explored.

Published
2008
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29. Comparison of Dialysis Unit and Home Blood Pressures: An Observational Cohort Study

Author

Miskulin, Dana C., Jiang, Huan, Gul, Ambreen, Pankratz, V. Shane, Paine, Susan S., Gassman, Jennifer J., Jhamb, Manisha, Kwong, Raymond Y., Negrea, Lavinia, Ploth, David W., Shaffi, Saeed Kamran, Harford, Antonia M., and Zager, Philip G.

Abstract

Prior studies of patients receiving maintenance hemodialysis have shown that, on average, blood pressure (BP) measured predialysis is higher than BP measured at home. We hypothesized that a subset of hemodialysis patients has BP that is higher when measured at home than when measured predialysis and this subgroup of patients has a higher prevalence of left ventricular hypertrophy.

Published
2021
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30. Predictors of Major Atrial Fibrillation Endpoints in the National Heart, Lung, and Blood Institute HCMR

Author

Kramer, Christopher M., DiMarco, John P., Kolm, Paul, Ho, Carolyn Y., Desai, Milind Y., Kwong, Raymond Y., Dolman, Sarahfaye F., Geller, Nancy, Kim, Dong-Yun, Maron, Martin S., Appelbaum, Evan, Jerosch-Herold, Michael, Friedrich, Matthias G., Schulz-Menger, Jeanette, Piechnik, Stefan K., Mahmod, Masliza, Jacoby, Daniel, White, James, Chiribiri, Amedeo, Helms, Adam, Choudhury, Lubna, Michels, Michelle, Bradlow, William, Salerno, Michael, Dawson, Dana K., Weinsaft, Jonathan W., Berry, Colin, Nagueh, Sherif F., Buccarelli-Ducci, Chiara, Casadei, Barbara, Watkins, Hugh, Weintraub, William S., and Neubauer, Stefan

Abstract

▪▪▪.

Published
2021
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34. State of the Art: Imaging for Myocardial Viability: A Scientific Statement From the American Heart Association

Author

Garcia, Mario J., Kwong, Raymond Y., Scherrer-Crosbie, Marielle, Taub, Cynthia C., Blankstein, Ron, Lima, João, Bonow, Robert O., Eshtehardi, Parham, and Bois, John P.

Abstract

A substantial proportion of patients with acute myocardial infarction develop clinical heart failure, which remains a common and major healthcare burden. It has been shown that in patients with chronic coronary artery disease, ischemic episodes lead to a global pattern of cardiomyocyte remodeling and dedifferentiation, hallmarked by myolysis, glycogen accumulation, and alteration of structural proteins. These changes, in conjunction with an impaired global coronary reserve, may eventually become irreversible and result in ischemic cardiomyopathy. Moreover, noninvasive imaging of myocardial scar and hibernation can inform the risk of sudden cardiac death. Therefore, it would be intuitive that imaging of myocardial viability is an essential tool for the proper use of invasive treatment strategies and patient prognostication. However, this notion has been challenged by large-scale clinical trials demonstrating that, in the modern era of improved guideline-directed medical therapies, imaging of myocardial viability failed to deliver effective guidance of coronary bypass surgery to a reduction of adverse cardiac outcomes. In addition, current available imaging technologies in this regard are numerous, and they target diverse surrogates of structural or tissue substrates of myocardial viability. In this document, we examine these issues in the current clinical context, collect current evidence of imaging technology by modality, and inform future directions.

Published
2020
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36. Abstract 13458: Prognostic Value of T1 Mapping and Feature Tracking by Cardiac Magnetic Resonance in Patients With Suspected Non-Ischemic Cardiomyopathy

Author

Seno, Ayako, Qamar, Iqra, Antiochos, Panagiotis, Ge, Yin, Chen, Yi-Yun, Aghayev, Ayaz, Steigner, Michael, Blankstein, Ron, Jerosch-Herold, Michael, and Kwong, Raymond Y

Abstract

Background:Impairment of systolic function is a well-known indicator of poor prognosis in patients with non-ischemic cardiomyopathy (NICM). It is, however, subject to limitations. Cardiac Magnetic Resonance (CMR) allows not only morphological and functional evaluation of Left Ventricle (LV), but also the quantification of remodeling. T1 mapping and LV strain by feature tracking are novel CMR techniques to evaluate for cardiac fibrosis and function. We aimed to evaluate the prognostic value of CMR-assessed T1 mapping and feature tracking LV strain in patients with suspected NICM.Methods and Results:N=349 consecutive patients with suspected NICM underwent CMR with T1 mapping and LV strain assessment, between 2015-2018. Global circumferential strain (GCS) and global longitudinal strain (GLS) were measured using feature tracking and extracellular volume (ECV) was obtained using Modified Look-Locker Inversion Recovery. The primary endpoint was major adverse cardiac events (MACE) defined as a composite of all-cause death, heart failure hospitalization and sustained ventricular arrhythmias. MACE occurred in 77/349 patients (22%) over a median follow-up of 17 months. Significant correlations were noted between GCS and LV ejection fraction (LVEF) and also between GCS and ECV (r=-0.923; p<0.001 & r =0.353; p<0.001 respectively). In the univariate analysis, significant clinical predictors of MACE included history of diabetes (hazard ratio [HR] 3.80; 95% confidence interval [CI] 1.49-9.69; p=0.005) and heart failure (HR 3.28; 95% CI 1.34-8.05; p=0.009), while significant imaging predictors included LVEF (HR 0.96; 95% CI 0.93-0.99; p=0.007), mean ECV (HR 1.10; 95% CI 1.05-1.14; p<0.001), GCS (HR 1.14; 95% CI 1.05-1.23; p=0.001) and GLS (HR 1.17; 95% CI 1.09-1.26; p<0.001). In the multivariate analysis, both ECV and GCS maintained a significant association with MACE (ECV: HR 1.06; 95% CI 1.02-1.11; p=0.008, GCS: HR 1.12; 95% CI 1.03-1.23; p=0.009). Finally, patients with both GCS ?-19% and ECV ?30% had the highest rates of MACE in the cohort.Conclusions:Our findings suggest that in patients with suspected NICM, the combined assessment of strain and ECV by CMR, might provide complementary prognostic value, on top of conventional risk factors and LVEF.

Published
2019
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37. Diagnostic Accuracy of Advanced Imaging in Cardiac Sarcoidosis

Author

Divakaran, Sanjay, Stewart, Garrick C., Lakdawala, Neal K., Padera, Robert F., Zhou, Wunan, Desai, Akshay S., Givertz, Michael M., Mehra, Mandeep R., Kwong, Raymond Y., Hedgire, Sandeep S., Ghoshhajra, Brian B., Taqueti, Viviany R., Skali, Hicham, Dorbala, Sharmila, Blankstein, Ron, and Di Carli, Marcelo F.

Abstract

Supplemental Digital Content is available in the text.

Published
2019
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39. Complementary Value of Cardiac Magnetic Resonance Imaging and Positron Emission Tomography/Computed Tomography in the Assessment of Cardiac Sarcoidosis

Author

Vita, Tomas, Okada, David R., Veillet-Chowdhury, Mahdi, Bravo, Paco E., Mullins, Erin, Hulten, Edward, Agrawal, Mukta, Madan, Rachna, Taqueti, Viviany R., Steigner, Michael, Skali, Hicham, Kwong, Raymond Y., Stewart, Garrick C., Dorbala, Sharmila, Di Carli, Marcelo F., and Blankstein, Ron

Abstract

Supplemental Digital Content is available in the text.

Published
2018
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40. Defining Quality in Cardiovascular Imaging: A Scientific Statement From the American Heart Association

Author

Shaw, Leslee J., Blankstein, Ron, Jacobs, Jill E., Leipsic, Jonathon A., Kwong, Raymond Y., Taqueti, Viviany R., Beanlands, Rob S.B., Mieres, Jennifer H., Flamm, Scott D., Gerber, Thomas C., Spertus, John, and Di Carli, Marcelo F.

Abstract

The aims of the current statement are to refine the definition of quality in cardiovascular imaging and to propose novel methodological approaches to inform the demonstration of quality in imaging in future clinical trials and registries. We propose defining quality in cardiovascular imaging using an analytical framework put forth by the Institute of Medicine whereby quality was defined as testing being safe, effective, patient-centered, timely, equitable, and efficient. The implications of each of these components of quality health care are as essential for cardiovascular imaging as they are for other areas within health care. Our proposed statement may serve as the foundation for integrating these quality indicators into establishing designations of quality laboratory practices and developing standards for value-based payment reform for imaging services. We also include recommendations for future clinical research to fulfill quality aims within cardiovascular imaging, including clinical hypotheses of improving patient outcomes, the importance of health status as an end point, and deferred testing options. Future research should evolve to define novel methods optimized for the role of cardiovascular imaging for detecting disease and guiding treatment and to demonstrate the role of cardiovascular imaging in facilitating healthcare quality.

Published
2017
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48. Myocardial Infarction Triggers Chronic Cardiac Autoimmunity in Type 1 Diabetes

Author

Gottumukkala, Raju V. S. R. K., Lv, HuiJuan, Cornivelli, Lizbeth, Wagers, Amy J., Kwong, Raymond Y., Bronson, Roderick, Stewart, Garrick C., Schulze, P. Christian, Chutkow, William, Wolpert, Howard A., Lee, Richard T., and Lipes, Myra A.

Abstract

Acute myocardial infarction triggers an autoimmune attack on the heart in a mouse model of type 1 diabetes and in human type 1 diabetic patients.

Published
2012
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49. Does Iron Overload Really Matter in Stem Cell Transplantation?

Author

Armand, Philippe, Sainvil, Marie-Michele, Kim, Haesook T, Rhodes, Joanna, Cutler, Corey, Ho, Vincent T, Koreth, John, Alyea, Edwin P, Neufeld, Ellis J., Kwong, Raymond Y, Soiffer, Robert J., and Antin, Joseph H.

Abstract

In patients with hematologic malignancies undergoing myeloablative hematopoietic stem cell transplantation (HSCT), an elevated serum ferritin prior to HSCT has been consistently associated with increased mortality. While serum ferritin is strongly correlated with liver iron content (LIC), to date no study has directly examined the effect of elevated LIC on HSCT outcomes. Furthermore, there are no studies of pre-transplantation chelation in this population. We conducted 2 prospective studies in patients with AML, ALL, or MDS undergoing HSCT. In the first, 45 patients were followed for >1 year with serial measurements of serum iron parameters and liver and cardiac iron (by MRI). In the second, we treated patients with severe iron overload (ferritin ≥ 1000 ng/ml and liver iron content (LIC) ≥ 5 mg/gdw) with deferoxamine 50 mg/kg/d starting in the weeks prior to transplantation and continuing until day -1, with the goal of controlling labile plasma iron (LPI) and especially the expected conditioning-induced rise in LPI.The baseline characteristics of the patients on the observational study have been described in a prior publication (Armand et al., BBMT 2011). 5 patients (2 with AML in CR, 2 with AML and active disease, 1 with MDS) were enrolled on the chelation study; the median serum ferritin was 3, 746 ng/ml, and LIC 11.7 mg/gdw. They received deferoxamine for a median of 19 days before stem cell infusion. No significant drug-related toxicity occurred except for one episode of transient hypotension. There was no significant change in LIC after this short course of chelation. None of the 5 patients had a positive LPI assay before chelation or at the onset of conditioning; however, despite deferoxamine treatment, 2/5 had elevated LPI post-conditioning. Among those 5 patients, there was no disease relapse or death at a median follow-up of 20 months; only 1 patient developed grade II acute GVHD, and no patient developed VOD.Among the 50 patients in both studies combined, there was no significant change in serum ferritin, LIC or cardiac T2* in the first year after HSCT. After a median follow-up of 24 months, the estimated 2y overall survival (OS) and progression-free survival were 54% and 46%, respectively. When patients on the chelation study were excluded, there was a significant difference in OS for patients with pre-HSCT ferritin > 2, 500 ng/ml (2y OS 21% versus 62%, p =0.03) (Figure, panel A), similar to prior studies. However, there was no difference in OS, PFS, relapse or NRM for patients stratified by pre-HSCT LIC, regardless of the cutoff used and whether or not chelated patients were included (Figure, panel B). There was also no discernible impact of LIC on acute GVHD or VOD incidence. The difference in OS based on ferritin was apparent even among the patients with LIC<5 mg/gdw. Those results were confirmed in multivariable analyses.We confirmed prospectively that pre-HSCT ferritin is an important prognostic marker in patients with AML, ALL or MDS undergoing HSCT. However, despite the strong correlation between ferritin and LIC, elevated LIC does not itself appear to be associated with survival. Thus, the prognostic value of ferritin may reflect other factors, such as inflammatory state, rather than iron burden. This calls into question the negative adverse impact attributed to iron overload in this population. Pre-transplantation chelation is challenging and does not reliably prevent the rise in LPI with conditioning. Despite this, our results in a very small number of patients raise the question of a possible beneficial effect of deferoxamine administered before HSCT that may be independent of parenchymal or labile iron chelation.Armand: Novartis Oncology: Research Funding. Neufeld:Novartis: Research Funding; Ferrokin BioSciences: Research Funding.

Published
2011
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50. ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis: Part 2 of 2-Diagnostic criteria and appropriate utilization.

Author

Dorbala S, Ando Y, Bokhari S, Dispenzieri A, Falk RH, Ferrari VA, Fontana M, Gheysens O, Gillmore JD, Glaudemans AWJM, Hanna MA, Hazenberg BPC, Kristen AV, Kwong RY, Maurer MS, Merlini G, Miller EJ, Moon JC, Murthy VL, Quarta CC, Rapezzi C, Ruberg FL, Shah SJ, Slart RHJA, Verberne HJ, and Bourque JM

Subjects
Biopsy, Cardiac Imaging Techniques standards, Consensus, Delphi Technique, Echocardiography, Heart Failure, Heart Ventricles, Humans, Multimodal Imaging, Prealbumin genetics, Societies, Medical, United States, Amyloidosis diagnostic imaging, Cardiology organization & administration, Cardiology standards, Heart diagnostic imaging
Abstract

Cardiac amyloidosis is emerging as an underdiagnosed cause of heart failure and mortality. Growing literature suggests that a noninvasive diagnosis of cardiac amyloidosis is now feasible. However, the diagnostic criteria and utilization of imaging in cardiac amyloidosis are not standardized. In this paper, Part 2 of a series, a panel of international experts from multiple societies define the diagnostic criteria for cardiac amyloidosis and appropriate utilization of echocardiography, cardiovascular magnetic resonance imaging, and radionuclide imaging in the evaluation of patients with known or suspected cardiac amyloidosis.

Published
2020
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