Predictors of Rapid Aortic Root Dilation and Referral for Aortic Surgery in Marfan Syndrome
Arvind Hoskoppal, Shaji Menon, Felicia Trachtenberg, Kristin M Burns, Julie De Backer, Bruce D Gelb, Marie Gleason, Jeanne James, Wyman W Lai, Aimee Liou, Lynn Mahony, Aaron K Olson, Reed E Pyeritz, Angela M Sharkey, Mario Stylianou, Stephanie Burns Wechsler, Luciana Young, Jami C Levine, Elif Seda Selamet Tierney, Ronald V Lacro, Timothy J Bradley, Pediatric Heart Network Investigators, Gail Pearson, Mario Stylianou, Victoria Pemberton, Lynn Mahony, Lynn Sleeper, Sharon Tennstedt, Steven Colan, Gloria Klein, Lin Guey, Lisa Wruck, Thomas Travison, Shan Chen, Eric Gerstenberger, Tanya Olesker, David F Teitel, Jane Newburger, Ronald V Lacro, Martha King, Carolyn Dunbar-Masterson, Jill Handisides, Andrea Posa, Quincy Nang, Cara Hass, Daphne Hsu, Wyman Lai, William Hellenbrand, Beth Printz, Mary J Roman, Richard Devereux, Rosalind Korsin, Greysi Sherwood, Victoria Vetter, Stephen Paridon, Marie Gleason, Reed Pyeritz, Nicole Mirarchi, Sandra DiLullo, Agbenu Ejembi, Ruth Morgan, Tonia Morrison, D Woodrow Benson, William Border, James Cnota, Haleh Heydarian, Jeanne James, Michelle Hamstra, Kathryn Hogan, Lois Bogenschutz, Page A W Anderson, Jennifer S Li, Stephanie Burns Wechsler, Amanda Cook, Charles Sang, Wesley Covitz, Mingfen Xu, Lori Jo Sutton, Kari Crawford, Summer Roberts, Deborah Palmer, J Philip Saul, Andrew Atz, Geoffrey Forbus, Teresa Atz, Patricia Infinger, Aparna Choudhury, LuAnn Minich, Richard Williams, Angela Yetman, Marian Shearrow, Michelle Robinson, June Porter, Brian McCrindle, Timothy J Bradley, Jennifer Russell, Jack Colman, Elizabeth Radojewski, Svetlana Khaikin, Nancy Slater, Harry C Dietz, William J Ravekes, Mary Rykiel, Elisabeth Sparks, Gretchen Oswald, Jennifer Leadroot, Charles Canter, Angela Sharkey, Alan Braverman, Cheryl Rainey, John L Jefferies, Timothy Slesnick, Aimee Liou, Hugo Martinez, Andres Menesses, Tunu Tenende, David Liang, Elisabeth Merkel, Bart Loeys, Julie De Backer, Jan Maarten Cobben, Thierry Sluysmans, Anne De Paepe, Sylvia De Nobele, Bruce Gelb, Shubhika Srivastava, Tejani Mendiz-Ramdeen, Constance Weismann, Emily Lawrence, Stephanie Chin, Helen Ko, Jen Le Yau, Steven Webber, Stacey Drant, Jane Luce, Kevin Stiegler, Larry Markham, Cheryl Kinnard, Cheri Stewart, Sue Sommers, Carol Madison, Luciana Young, Megan Domenico, Kathryn Waitzman, Carla Lozano, Mary Ella Pierpont, Charles Baker, Erin Zielinski, Heidi Vander Velden, Alison Overman, Mark Lewin, Aaron Olson, Amy Payne, David Rimoin, Mitchel Pariani, Robert Siegel, Asim Rafique, Paul Grossfeld, Arlene Smith, Terri McLees-Palinkas, Steven D Colan, Elif Seda Selamet Tierney, Jami Levine, Shari Trevey, Marga Rivera, Michael Artman, Erle Austin, H Scott Baldwin, Daniel Bernstein, Timothy Feltes, Julie Johnson, Thomas Klitzner, Jeffrey Krischer, G Paul Matherne, Kenneth G Zahka, John Kugler, David J Driscoll, Mark Galantowicz, Sally A Hunsberger, Thomas J Knight, Holly Taylor, Arvind Hoskoppal, Shaji Menon, Felicia Trachtenberg, Kristin M Burns, Julie De Backer, Bruce D Gelb, Marie Gleason, Jeanne James, Wyman W Lai, Aimee Liou, Lynn Mahony, Aaron K Olson, Reed E Pyeritz, Angela M Sharkey, Mario Stylianou, Stephanie Burns Wechsler, Luciana Young, Jami C Levine, Elif Seda Selamet Tierney, Ronald V Lacro, Timothy J Bradley, Pediatric Heart Network Investigators, Gail Pearson, Mario Stylianou, Victoria Pemberton, Lynn Mahony, Lynn Sleeper, Sharon Tennstedt, Steven Colan, Gloria Klein, Lin Guey, Lisa Wruck, Thomas Travison, Shan Chen, Eric Gerstenberger, Tanya Olesker, David F Teitel, Jane Newburger, Ronald V Lacro, Martha King, Carolyn Dunbar-Masterson, Jill Handisides, Andrea Posa, Quincy Nang, Cara Hass, Daphne Hsu, Wyman Lai, William Hellenbrand, Beth Printz, Mary J Roman, Richard Devereux, Rosalind Korsin, Greysi Sherwood, Victoria Vetter, Stephen Paridon, Marie Gleason, Reed Pyeritz, Nicole Mirarchi, Sandra DiLullo, Agbenu Ejembi, Ruth Morgan, Tonia Morrison, D Woodrow Benson, William Border, James Cnota, Haleh Heydarian, Jeanne James, Michelle Hamstra, Kathryn Hogan, Lois Bogenschutz, Page A W Anderson, Jennifer S Li, Stephanie Burns Wechsler, Amanda Cook, Charles Sang, Wesley Covitz, Mingfen Xu, Lori Jo Sutton, Kari Crawford, Summer Roberts, Deborah Palmer, J Philip Saul, Andrew Atz, Geoffrey Forbus, Teresa Atz, Patricia Infinger, Aparna Choudhury, LuAnn Minich, Richard Williams, Angela Yetman, Marian Shearrow, Michelle Robinson, June Porter, Brian McCrindle, Timothy J Bradley, Jennifer Russell, Jack Colman, Elizabeth Radojewski, Svetlana Khaikin, Nancy Slater, Harry C Dietz, William J Ravekes, Mary Rykiel, Elisabeth Sparks, Gretchen Oswald, Jennifer Leadroot, Charles Canter, Angela Sharkey, Alan Braverman, Cheryl Rainey, John L Jefferies, Timothy Slesnick, Aimee Liou, Hugo Martinez, Andres Menesses, Tunu Tenende, David Liang, Elisabeth Merkel, Bart Loeys, Julie De Backer, Jan Maarten Cobben, Thierry Sluysmans, Anne De Paepe, Sylvia De Nobele, Bruce Gelb, Shubhika Srivastava, Tejani Mendiz-Ramdeen, Constance Weismann, Emily Lawrence, Stephanie Chin, Helen Ko, Jen Le Yau, Steven Webber, Stacey Drant, Jane Luce, Kevin Stiegler, Larry Markham, Cheryl Kinnard, Cheri Stewart, Sue Sommers, Carol Madison, Luciana Young, Megan Domenico, Kathryn Waitzman, Carla Lozano, Mary Ella Pierpont, Charles Baker, Erin Zielinski, Heidi Vander Velden, Alison Overman, Mark Lewin, Aaron Olson, Amy Payne, David Rimoin, Mitchel Pariani, Robert Siegel, Asim Rafique, Paul Grossfeld, Arlene Smith, Terri McLees-Palinkas, Steven D Colan, Elif Seda Selamet Tierney, Jami Levine, Shari Trevey, Marga Rivera, Michael Artman, Erle Austin, H Scott Baldwin, Daniel Bernstein, Timothy Feltes, Julie Johnson, Thomas Klitzner, Jeffrey Krischer, G Paul Matherne, Kenneth G Zahka, John Kugler, David J Driscoll, Mark Galantowicz, Sally A Hunsberger, Thomas J Knight, Holly Taylor
Abstract
Few data exist regarding predictors of rapid aortic root dilation and referral for aortic surgery in Marfan syndrome (MFS). To identify independent predictors of the rate of aortic root (AoR) dilation and referral for aortic surgery, we investigated the data from the Pediatric Heart Network randomized trial of atenolol versus losartan in young patients with MFS. Data were analyzed from the echocardiograms at 0, 12, 24, and 36 months read in the core laboratory of 608 trial subjects, aged 6 months to 25 years, who met original Ghent criteria and had an AoR z-score (AoRz) > 3. Repeated measures linear and logistic regressions were used to determine multivariable predictors of AoR dilation. Receiver operator characteristic curves were used to determine cut-points in AoR dilation predicting referral for aortic surgery. Multivariable analysis showed rapid AoR dilation as defined by change in AoRz/year > 90th percentile was associated with older age, higher sinotubular junction z-score, and atenolol use (R2 = 0.01) or by change in AoR diameter (AoRd)/year > 90th percentile with higher sinotubular junction z-score and non-white race (R2 = 0.02). Referral for aortic root surgery was associated with higher AoRd, higher ascending aorta z-score, and higher sinotubular junction diameter:ascending aorta diameter ratio (R2 = 0.17). Change in AoRz of 0.72 SD units/year had 42% sensitivity and 92% specificity and change in AoRd of 0.34 cm/year had 38% sensitivity and 95% specificity for predicting referral for aortic surgery. In this cohort of young patients with MFS, no new robust predictors of rapid AoR dilation or referral for aortic root surgery were identified. Further investigation may determine whether generalized proximal aortic dilation and effacement of the sinotubular junction will allow for better risk stratification. Rate of AoR dilation cut-points had high specificity, but low sensitivity for predicting referral for aortic surgery, limiting their clinical use. Clinical Trial Number ClinicalTrials.gov number, NCT00429364.
Keywords: Aortic root dilation; Marfan syndrome; Predictors; Referral for aortic surgery.
Conflict of interest statement
Compliance with Ethical Standards
Conflict of interest/Relation to Industry The authors do not have any conflict of interest. The views expressed in this article are those of the authors and do not represent the official views of the National Heart, Lung, and Blood Institute (NHLBI) or the National Institutes of Health.
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Source: PubMed