Long-term implications of emergency versus elective proximal aortic surgery in Marfan syndrome patients in the GenTAC Registry

Objective—Marfan syndrome patients with aortic root aneurysms undergo elective aortic root replacement to avoid the life-threatening outcomes of aortic dissection and emergency repair. The long-term implications of failed aortic surveillance leading to acute dissection and emergency repair are poorly defined. We compared the long-term clinical courses of Marfan syndrome patients who survive emergency versus elective proximal aortic surgery. Methods—The GenTAC Registry is an NIH-funded, multicenter database and biorepository that enrolls patients with genetically triggered thoracic aortic aneurysms. Of the 635 patients with Marfan syndrome enrolled as of March 2011, 194 had undergone proximal aortic replacement. Patients were grouped according to emergent (n=47) or elective (n=147) status at the time of surgery. Results—Patients in the emergent group were more likely to have incomplete proximal aortic resection; 83% of emergency procedures included aortic root replacement, compared with 95% of © 2011 The American Association For Thoracic Surgery. Published by Mosby, Inc. All rights reserved. Corresponding Author: Howard K. Song, M.D., Ph.D., Associate Professor, Division of Cardiothoracic Surgery, Oregon Health & Science University, Mail Code L353, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, Office: 503-494-7820, Fax: 503-494-7829, songh@ohsu.edu. The authors have no potential conflicts of interest to report. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author Manuscript J Thorac Cardiovasc Surg. Author manuscript; available in PMC 2013 February 1. Published in final edited form as: J Thorac Cardiovasc Surg. 2012 February ; 143(2): 282–286. doi:10.1016/j.jtcvs.2011.10.024. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript elective procedures. At long-term follow-up (mean, >6 years), emergent patients had a higher incidence of chronic dissection of the distal aorta and had significantly larger diameters in distal aortic segments than elective patients. Additionally, emergent patients had undergone more operations (1.31 vs 1.11 procedures/patient; P=0.01) and had lower activity scores on a healthrelated quality-of-life survey. Conclusions—For Marfan syndrome patients, failed aortic surveillance and consequent emergency dissection repair have important long-term implications with regard to status of the distal aorta, the need for multiple procedures, and quality of life. These findings emphasize the importance of aortic surveillance and timely elective aortic root aneurysm repair for Marfan syndrome patients. Marfan syndrome is an autosomal dominant inherited disorder caused by mutations in the gene that encodes fibrillin-1. The syndrome is characterized by systemic connective tissue manifestations involving the ocular, skeletal, and cardiovascular systems, among others. Cardiovascular complications, especially aortic root dissection and rupture, are the most common causes of death; their peak incidence is in the third and fourth decades of life.1–4 The life expectancy of Marfan syndrome patients has dramatically improved since aortic root replacement with a composite prosthetic valve conduit was first reported by Bentall in 1967.5,6 Composite valve graft procedures and valve-sparing aortic root replacement procedures are now routinely performed under elective conditions, with low morbidity and mortality.7–12 Patients with Marfan syndrome typically undergo aortic surveillance with serial imaging of the aortic root and are offered elective aortic root replacement when their aortic root diameter reaches an appropriate size in order to avoid life-threatening aortic dissection and the high morbidity associated with emergency aortic surgery. Although the immediate risk of aortic dissection and emergency repair for this patient population has been extensively studied, the long-term implications of failed aortic surveillance and emergency dissection repair are poorly defined.13–20 The National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC)21,22 has established a biospecimen repository and bioinformatics infrastructure to enable research to determine best practices for optimal clinical management of genetically triggered thoracic aortic aneurysms and related complications. We used the GenTAC Registry to compare the long-term clinical course of Marfan syndrome patients who survive emergency versus elective proximal aortic surgery. MATERIALS AND METHODS GenTAC Registry The GenTAC Registry contains longitudinal observational data on patients with conditions related to genetically induced thoracic aortic aneurysms.21,22 It also has a biospecimen repository and bioinformatics infrastructure created to support research to determine the optimal clinical management of genetically triggered thoracic aortic aneurysms and related complications. The National Heart Lung and Blood Institute and the National Institute of Arthritis and Musculoskeletal and Skin Diseases are co-sponsors of GenTAC. Patients included in this study were recruited from 5 regional clinical centers that treat patients from a wide geographic catchment area within the United States: Johns Hopkins University, Oregon Health & Science University, University of Pennsylvania, University of Texas Health Science Center at Houston/Baylor College of Medicine, and Weill Cornell Medical College. Research Triangle Institute International serves as the data coordinating center responsible for data management, coordination of training, logistics, and statistical design and analysis. Song et al. Page 2 J Thorac Cardiovasc Surg. Author manuscript; available in PMC 2013 February 1. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript The targeted enrollment of patients includes adults and children who fall into 1 or more of 12 diagnosis categories, including Marfan syndrome, Loeys-Dietz syndrome, vascular Ehlers-Danlos syndrome, Turner syndrome, bicuspid aortic valve with ascending aortic aneurysm, and familial thoracic aortic aneurysm and dissection. Available clinical data, imaging results, and blood and tissue samples from each patient are processed and stored by GenTAC to provide a resource that combines clinical and biological data from a large and diverse population of patients with inherited thoracic aortic aneurysm disorders. Patients From the 635 patients with Marfan syndrome who were enrolled in GenTAC as of March 2011, we selected those who had undergone proximal aortic replacement procedures. Our analyses focused on procedure information, imaging findings, and quality of life, which was measured with the Activity Score of the SF-36 Health Survey23 and the Karnofsky Performance Status Score.24 Analysis We used SAS software (SAS Institute, Inc.; Cary, NC) to extract data from the secure enterprise network database to create reports and summary tables and to perform ad hoc statistical analyses. To examine between-group differences in continuous outcomes, we used t-tests when tests of normality confirmed that the outcomes data were normally distributed. Wilcoxon rank-sum tests were used when continuous outcome data did not follow a normal distribution. To examine between-group differences in categorical outcomes, we used χ2 tests unless the sample sizes were small, in which case Fisher exact tests were performed. For data security purposes, all analyses were performed and all data were stored in a password-protected remote workspace. Institutional Review Boards and Consent Institutional Review Board approval was obtained for this study at each of the 5 participating GenTAC regional clinical centers. Individual informed consent was obtained from each GenTAC Registry patient.