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The BAVgenetics Investigators want to find the genetic causes of bicuspid aortic valve disease and aortic aneurysm and dissection that are also associated with bicuspid aortic valve disease.
Dr. Simon Body, Associate Professor of Anaesthesia at Harvard Medical School, is the Vice Chair of Research and a cardiac anesthesiologist in the Department of Anesthesia, Critical Care and Pain Medicine at Beth Israel Deaconess Medical Center. His academic interest is the role of genetic variation upon postoperative outcomes after cardiac surgery. In addition he is particularly interested in the role of genetic variation in bicuspid aortic valve disease.
Bicuspid Aortic Valve
A bicuspid aortic valve (BAV) has two leaflets, not the usual three. It is relatively common in the population with a rate of 0.6-1.5%; higher in males and Caucasians, and is the most common congenital valve disease (Yang et al. 2017). BAV comes with a propensity towards ascending aortic dilation and aneurysm and a very high rate of aortic stenosis and incompetence. Patients with a BAV commonly need surgery to replace the aortic valve because it has become stenotic or incompetent, or the ascending aorta is aneurysmal. This increased risk is about 10-15-fold higher than if they had a normal tricuspid aortic valve, and on average this surgery is performed in their 50’s to 60’s, about 15-20 years earlier than if they had a normal tricuspid aortic valve. So, it is a good-size health burden for people.
In 2005, the first variants in a gene for BAV was identified; a gene called NOTCH1that has a very important role in embryonic development. However, these variants have only been described in two families and other very-rare variants in or near NOTCH1 are not well associated with BAV. So these variants cannot explain the 0.6-1.5% rate of BAV in the population. We embarked on a genome-wide search for genetic causes of BAV in a cohort of patients collected locally and a through the International Bicuspid Aortic Valve Consortium, that I head. Early in 2017, we published our findings (Michelena et al. 2014), showing that common variants near GATA4 were associated with BAV development. This was an attractive finding as GATA4 is well known to have a major role in cardiac development, especially in left ventricular outflow tract development. It was also attractive because these were relatively-common variants, thus helping to explain the relatively high-frequency of BAV in the population. Presently, we are working on other aortic stenosis and BAV “hits” we identified in the genome-wide study.
Education / Training
Medical School: Auckland Medical School, Auckland, New Zealand
Residencies / Fellowships: Auckland Hospital, Auckland, New Zealand Brigham & Women’s Hospital, Boston, MA
Research Focus
The effect of genetic variation upon outcomes after cardiac surgery and the role of genetic variation in bicuspid aortic valve disease.
Representative Publications
Liu KY, Muehlschlegel JD, Perry TE, Fox AA, Collard CD, Body SC, Shernan SK. Common genetic variants on chromosome 9p21 predict perioperative myocardial injury after coronary artery bypass graft surgery. J Thorac Cardiovasc Surg. 2009 Oct 9. [Epub ahead of print] PubMed PMID: 19819472.
Aranki SF, Body SC. Antiplatelet agents used for early intervention in acute coronary syndrome: myocardial salvage versus bleeding complications. J Thorac Cardiovasc Surg. 2009 Oct;138(4):807-10. PubMed PMID: 19769880.
Perry TE, Muehlschlegel JD, Liu KY, Fox AA, Collard CD, Body SC, Shernan SK; CABG Genomics Investigators. C-Reactive protein gene variants are associated with postoperative C-reactive protein levels after coronary artery bypass surgery. BMC Med Genet. 2009 May 8;10:38. PubMed PMID: 19426506; PubMed Central PMCID: PMC2686694.
Muehlschlegel JD, Perry TE, Liu KY, Nascimben L, Fox AA, Collard CD, Avery EG, Aranki SF, D’Ambra MN, Shernan SK, Body SC; CABG Genomics Investigators. Troponin is superior to electrocardiogram and creatinine kinase MB for predicting clinically significant myocardial injury after coronary artery bypass grafting. Eur Heart J. 2009 Jul;30(13):1574-83. Epub 2009 Apr 30. PubMed PMID: 19406870; PubMed Central PMCID: PMC2733736.
Fox AA, Collard CD, Shernan SK, Seidman CE, Seidman JG, Liu KY, Muehlschlegel JD, Perry TE, Aranki SF, Lange C, Herman DS, Meitinger T, Lichtner P, Body SC. Natriuretic peptide system gene variants are associated with ventricular dysfunction after coronary artery bypass grafting. Anesthesiology. 2009 Apr;110(4):738-47. PubMed PMID: 19326473; PubMed Central PMCID: PMC2735337.
Fox AA, Shernan SK, Collard CD, Liu KY, Aranki SF, DeSantis SM, Jarolim P, Body SC. Preoperative B-type natriuretic peptide is as independent predictor of ventricular dysfunction and mortality after primary coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2008 Aug;136(2):452-61. PubMed PMID: 18692657; PubMed Central PMCID: PMC2739747.
Muehlschlegel JD, Body SC. Impact of genetic variation on perioperative bleeding. Am J Hematol. 2008 Sep;83(9):732-7. Review. PubMed PMID: 18508320.
Collard CD, Shernan SK, Fox AA, Bernig T, Chanock SJ, Vaughn WK, Takahashi K, Ezekowitz AB, Jarolim P, Body SC. The MBL2 ‘LYQA secretor’ haplotype is an independent predictor of postoperative myocardial infarction in whites undergoing coronary artery bypass graft surgery. Circulation. 2007 Sep 11;116(11 Suppl):I106-12. PubMed PMID: 17846289.
Contact
Simon C. Body, MD, MPH 375 Longwood Ave. MASCO 4th Fl. Room 412B Boston, MA 02115 Phone: (617) 632-8056 Email: sbody@BIDMC.harvard.edu
Thy B. Nguyen is a clinical research assistant to Dr. Simon Body for the investigation of the genetic etiologies of bicuspid aortic valve disease. With an interest in the intersection of maternal-fetal health and global health, she is working towards applying to medical school and is currently completing coursework at the Harvard Extension School Premedical Program. Outside of work at Beth Israel Deaconess Medical Center, she is a teaching assistant in health policy through the Petey Greene Program and serves as an officer for PureMadi, an organization that works to increase access to potable water and prevent waterborne illness.
Education / Training
Premedical Program, Harvard Extension School, Cambridge, MA (2017 – present)
Bachelor of Arts in Biology, Specialization in Environmental and Biological Conservation: The University of Virginia, Charlottesville, VA (2010-2014)
Contact
Thy B. Nguyen 375 Longwood Ave. MASCO 4th Floor Boston, MA 02115 Phone: (617) 632-8048
Jasmine T. Shahram is a clinical research coordinator for the CABG Genomics Program at Beth Israel Deaconess Medical Center and has been part of the team since 2015. She earned her Bachelor of Science degree in Psychology from Suffolk University in Boston, M.A. Her current role primarily focuses on identifying genetic variations associated with bicuspid aortic valve disease, as well as coordinating with Investigators throughout BAVCon (The Bicuspid Aortic Valve Consortium; an international consortium of 26+ institutions gathered worldwide with cohorts of BAV patients).
Education / Training
Bachelor of Science in Psychology, Suffolk University, Boston, Massachusetts (2011-2015)
Representative Publications
Association between bicuspid aortic valve morphotype and regional dilatation of the aortic root and trunk. Karam M. Habchi, Elena Ashikhmina, Vanessa Montiero Vieira, Jasmine T. Shahram, Eric M. Isselbacher, Thoralf M. Sundt III, Prem Shekar, Jochen D. Muehlschlegel, Bicuspid Aortic Valve Consortium, and Simon C. Body
Genome Wide Association with Aortic Dimension in Bicuspid Aortic Valve Disease. Mahyar Heydarpour, PhD, Martin Sigurdsson, M.D., Ph.D., Vanessa Montiero Vieira, B.S., Jasmine T. Shahram, B.S., J. Daniel Muehlschlegel, M.D., M.M.Sc., Tsuyoshi Kaneko, M.D., Prem Shekar, M.D., Thoralf M. Sundt III, M.D., Simon C. Body, M.B.,Ch.B., M.P.H.
Should the Dilated Ascending Aorta be repaired at the time of Bicuspid Aortic Valve Replacement? Tsuyoshi Kaneko, M.D., Prem Shekar, M.D., Vladimir Ivkovic, Ph.D., Nicholas T. Longford, Ph.D., Chuan-Chin Huang, D.Sc., Martin Sigurdsson, M.D., Ph.D., Robert C. Neely, M.D., Maroun Yammine, M.D., Julius Ejilofor, M.D., Vanessa Montiero Vieira, B.S., Jasmine T. Shahram, B.S., Karam M. Habchi, M.S., Gregory W. Malzberg, B.A., Jordan Bloom, M.D., Eric M. Isselbacher, M.D., J. Daniel Muehlschlegel, M.D., M.M.Sc., Bicuspid Aortic Valve Consortium (BAVCon), Thoralf M. Sundt III, M.D.
Pathogenic Mechanisms of Bicuspid Aortic Valve Aortopathy. Noor M. Yassine, B.S., Jasmine T. Shahram, B.S., Simon C. Body, M.D., M.P.H.
Contact
Jasmine T. Shahram 375 Longwood Ave. MASCO 4th Floor Boston, MA 02115 Phone: (617) 632-8067
Dr. Xinling Xu, who goes by Claire, is a biostatistician in anesthesiology at Beth Israel Deaconess Medical Center. Her primary research interests are the applications of various statistical techniques in pain management, and anesthesia. Her expertise lies in Bayesian factor analysis, generalized estimating equations and generalized linear mixed effect models for longitudinal data/repeated measures, complex survey data analysis, sample size calculation, as well as the application of copula functions for bivariate outcomes.
Education / Training
PhD in Biostatistics: University of South Carolina, Columbia, SC (2013-2017)
MS in Statistics: University of Minnesota, Twin Cities, MN (2011-2013)
BS in Computational Mathematics: Dalian University of Technology, China (2007-2011)
If you have any questions or concerns about this research that you would like answered by the staff of the Committee on Clinical Investigations (CCI), is the institutional review board (IRB) for the Beth Israel Deaconess Medical Center,
You may write to: Beth Israel Deaconess Medical Center CCI/IRB 330 Brookline Ave. Boston, MA 02215 Or telephone: 617-754-2670
Simon C. Body, MD, MPH, FAHA
Thy B. Nguyen
Jasmine T. Shahram
Xinling (Claire) Xu, PhD
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