CHSS Kirklin/Ashburn Fellowship: Legacy and Promise

The Congenital Heart Surgeons’ Society (CHSS) Data Center has been the academic research engine for the CHSS for over 30 years. It provides high-quality, evidence-based analyses of the surgical management and longitudinal outcomes of patients with important forms congenital heart disease. The Data Center originated as an effort to overcome the challenges related to the relatively low prevalence of many specific congenital heart defects and the resultant difficulty in learning ways to optimize the management of these patients. Drs. John W. Kirklin and Eugene H. Blackstone established the Data Center at the University of Alabama at Birmingham in 1985 to pool the collective experience of member surgeons and their institutions. In 2001, the Data Center, by then housed at the Hospital for Sick Children in Toronto, initiated a clinical research fellowship for a surgical resident interested in pursuing a career in congenital heart surgery.

The CHSS Fellowship provides advanced education in data management and statistical analysis of surgical management strategies for congenital heart disease. All fellows have made substantial contributions to the field of congenital heart disease. Several fellows have also simultaneously obtained a post-graduate degree from the University of Toronto. The fellowship was named for Dr. John W. Kirklin, a pioneer of cardiothoracic surgery whose contributions to the field are legendary, and Dr. David Ashburn, the first recipient of the fellowship, who was tragically killed in an airplane crash while on an organ procurement trip as a cardiothoracic surgery resident at the University of Michigan.

The mission of the CHSS Data Center is to “improve care for patients with congenital heart disease through collaborative research on behalf of the Congenital Heart Surgeons Society and our patients.” The Data Center maintains 11 prospective, diagnosis-based inception cohorts of patients with several rare forms of congenital heart disease. An inception cohort implies patient selection based upon a diagnosis at the initial admission to any CHSS institution. Therefore the Data Center studies, with few exceptions, are designed to discover the longitudinal outcomes of patients of all treatment modalities from birth to death, not simply to report operative morbidity and mortality. Among the 11 CHSS cohort studies, four are currently enrolling patients, including critical left ventricular outflow tract obstruction (LVOTO), atrioventricular septal defect (AVSD), anomalous aortic origin of the coronary arteries (AAOCA), and tricuspid atresia. Patients in the seven remaining cohorts, which are not currently enrolling new patients, continue to be followed annually. A new cohort of patients with Ebstein anomaly is planned to begin enrollment in late 2016.

At the CHSS Data Center, the Kirklin/Ashburn Fellow has secure access to the data for the clinical and operative courses of thousands of patients. Participating institutions send all patient procedure records, clinic notes, echocardiographic reports, and other study reports to the Data Center. From this information, data are meticulously extracted by the Data Center’s clinical research staff. Recently, an imaging core lab has reviewed and provided highly reliable data from large numbers of echocardiograms from children with critical LVOTO, AVSD, and AAOCA.

The fellow receives methodologic education and guidance in advanced longitudinal survival analytic techniques from Dr. Eugene Blackstone and his statistical colleagues at the Cleveland Clinic, and from Dr. Brian McCrindle in Toronto. Comprehensive reviews of the Data Center’s statistical methods have been published by Caldarone, et al. and Hickey, et al, including parametric risk hazard analysis, competing risks analysis, modulated renewal, the longitudinal analysis of repeated measures, and more (1, 2). These complex methods represent an attempt to account for the myriad challenges of analyzing outcomes of neonates and children with congenital heart defects, chief among them being the low prevalence of many congenital lesions, their broad morphologic spectra, and the variety of management strategies employed at different institutions. This approach enables the CHSS to perform time-to-event analyses of lesions and management strategies that may never be amenable to a randomized clinical trial. The introduction of extensions of these techniques has allowed the CHSS to answer clinically important by analytically challenging questions, such as survival through staged procedures or how the risk of death changes with individual re-interventions.

The fellow is involved in all aspects of a CHSS study, including: proposal generation, study design, statistical programming and analysis, abstract writing, presentation at national and international meetings, and manuscript generation. One of the most valuable aspects of the fellowship are the biannual Work Weekends, events during which the fellow presents preliminary summaries and analyses of ongoing studies for discussion and guidance by the 20 to 30 surgeons typically in attendance. These Work Weekends are not only opportunities to have results and conclusions scrutinized by surgeons from across North America, but for the fellow to hone presentation and writing skills.

Previous fellows have made important contributions to the congenital heart disease literature and have presented the Data Center’s work at prestigious meetings in cardiac surgery and cardiology, including at meetings of the American Association for Thoracic Surgery, The Society of Thoracic Surgeons, the American Heart Association, and the annual scientific meetings of the CHSS. Dr. David Ashburn published five analyses covering a variety of congenital cardiac defects (tricuspid atresia, transposition of the great arteries, aortic valve atresia, and aortic valve stenosis), while earning his Master’s degree based on the application of competing risks methodology to congenital heart disease management (3, 4). Dr. Tara Karamlou, surgeon and Director of the Cardiovascular Research Institute at Phoenix Children’s Hospital, focused on complex outcomes of infants with interrupted aortic arch (5, 6). Dr. Edward Hickey, Assistant Professor of Surgery at Hospital for Sick Children, focused on patients with Critical LVOTO, particularly in decision-making for neonates with borderline-size left ventricles (7, 8). Dr. Anusha Jegastheewaran, who is in clinical training in congenital heart surgery at the Children’s Hospital of Philadelphia, earned a PhD in clinical epidemiology for her work on the risk of re-interventions in patients with interrupted aortic arch using modulated renewal methodology, a technique originally applied in industrial engineering (9). Dr. Jeffrey Poynter, who is beginning his cardiothoracic surgery fellowship at the University of Pennsylvania,  earned a Master’s degree analyzing time-dependent variables’ effects on the durability of pulmonary artery conduits in infants with truncus arteriosus (10). Dr. Travis Wilder, currently finishing general surgery residency at the University of California-San Diego, focused on comparing shunt types used during the Norwood operation employing propensity-matched analysis of outcomes (11). He also continued to build upon the Data Center’s expertise by analyzing how shunt type affected tricuspid valve and right ventricular function across time. With every fellow, the Data Center’s analyses evolve in focus and complexity. A full list of the publications from the CHSS Data Center and its fellows can be found at http://www.chssdc.org/publications.

The Data Center is currently engaged in a variety of projects with Dr. James Meza, the 8^th Kirklin/Ashburn Fellow and a general surgery resident at Duke University Hospital.  Four analyses of the critical LVOTO cohort are ongoing, highlighted by a study of the optimal timing of stage 2 palliation after the Norwood operation using conditional survival analysis and a data-driven approach to the classification of critical LVOTO using cluster analysis of the baseline echocardiograms of 651 such neonates. His Master’s thesis will introduce a novel application of dynamic risk profile methodology to provide updatable, patient-level predictions of the optimal timing of stage 2 palliation after the Norwood operation that aims to minimize “interstage” mortality and maximize long-term survival. Projects in the AAOCA and AVSD registries are in development as well.

Overall, the Kirklin/Ashburn Fellowship has become an integral part of the CHSS Data Center. Not only do fellows receive an unparalleled immersion in congenital heart disease and education in statistical analysis, but they have the opportunity to design, execute, and publish studies that are considered among the highest quality evidence in the field of congenital heart disease. The legacy of the Kirklin/Ashburn Fellowship continues to be elevated by every fellow and the promise of the opportunities afforded by the fellowship continues to look bright into the future.

Recruitment for the next fellow began in July 2016. Surgical residents interested in the K/A Fellowship should contact the CHSS Data Center at chss.dc@sickkids.ca. 

References

1. Hickey EJ, McCrindle BW, Caldarone CA, Williams WG, Blackstone EH. Making sense of congenital cardiac disease with a research database: The Congenital Heart Surgeons' Society Data Center. Cardiology in the young 2008 Dec;18 Suppl 2:152-62.
2. Caldarone CA, Williams WG. The Congenital Heart Surgeons Society Datacenter: unique attributes as a research organization. Seminars in thoracic and cardiovascular surgery Pediatric cardiac surgery annual 2010;13(1):71-5.
3. Ashburn DA, McCrindle BW, Tchervenkov CI, Jacobs ML, Lofland GK, Bove EL, et al. Outcomes after the Norwood operation in neonates with critical aortic stenosis or aortic valve atresia. The Journal of thoracic and cardiovascular surgery 2003 May;125(5):1070-82.
4. Williams WG, McCrindle BW, Ashburn DA, Jonas RA, Mavroudis C, Blackstone EH, et al. Outcomes of 829 neonates with complete transposition of the great arteries 12-17 years after repair. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 2003 Jul;24(1):1-9; discussion -10.
5. Konstantinov IE, Karamlou T, Blackstone EH, Mosca RS, Lofland GK, Caldarone CA, et al. Truncus arteriosus associated with interrupted aortic arch in 50 neonates: a Congenital Heart Surgeons Society study. The Annals of thoracic surgery 2006 Jan;81(1):214-22.
6. Konstantinov IE, Karamlou T, Williams WG, Quaegebeur JM, del Nido PJ, Spray TL, et al. Surgical management of aortopulmonary window associated with interrupted aortic arch: a Congenital Heart Surgeons Society study. The Journal of thoracic and cardiovascular surgery 2006 May;131(5):1136-41 e2.
7. Hickey EJ, Caldarone CA, Blackstone EH, Lofland GK, Yeh T, Jr., Pizarro C, et al. Critical left ventricular outflow tract obstruction: The disproportionate impact of biventricular repair in borderline cases. The Journal of thoracic and cardiovascular surgery 2007 Dec;134(6):1429-36; discussion 36-7.
8. Hickey EJ, Caldarone CA, Blackstone EH, Williams WG, Yeh T, Jr., Pizarro C, et al. Biventricular strategies for neonatal critical aortic stenosis: high mortality associated with early reintervention. The Journal of thoracic and cardiovascular surgery 2012 Aug;144(2):409-17, 17 e1.
9. Jegatheeswaran A, McCrindle BW, Blackstone EH, Jacobs ML, Lofland GK, Austin EH, 3rd, et al. Persistent risk of subsequent procedures and mortality in patients after interrupted aortic arch repair: a Congenital Heart Surgeons' Society study. The Journal of thoracic and cardiovascular surgery 2010 Nov;140(5):1059-75 e2.
10. Poynter JA, Eghtesady P, McCrindle BW, Walters HL, 3rd, Kirshbom PM, Blackstone EH, et al. Association of pulmonary conduit type and size with durability in infants and young children. The Annals of thoracic surgery 2013 Nov;96(5):1695-701; discussion 701-2.
11. Wilder TJ, McCrindle BW, Phillips AB, Blackstone EH, Rajeswaran J, Williams WG, et al. Survival and right ventricular performance for matched children after stage-1 Norwood: Modified Blalock-Taussig shunt versus right-ventricle-to-pulmonary-artery conduit. The Journal of thoracic and cardiovascular surgery 2015 Dec;150(6):1440-50, 52 e1-8; discussion 50-2.