Single ventricle heart defects, where systemic and pulmonary venous returns mix in the single functional ventricle, represent the most complex form of congenital heart defect. Surgical repairs, termed """"""""Fontan Repairs,"""""""" reroute the systemic venous return directly to the pulmonary arteries, thus preventing venous return mixing and restoring normal oxygenation saturation levels. Unfortunately, these repairs are only palliative and Fontan patients are subjected to a multitude of chronic complications. Over the past 20 years, researchers have sought to understand the hemodynamics through this surgical construct in an effort to optimize its efficiency and minimize the imposed workload on the single ventricle. While this work has led to important advances in the surgical approach, including the development of the total cavopulmonary connection (TCPC), an integrated experimental and clinical approach relating these quantitative markers to ultimate patient outcomes has been lacking. Such a study would represent a critical step in the advancement of treatment efforts as it will identify the clinical markers that control outcomes, and elucidate the mechanisms of Fontan failure. Understanding these interconnections would also provide the means to develop optimal medical strategies to improve those outcomes. Therefore, the objective of this grant is to investigate the relationship between TCPC hemodynamics and ventricular function, and subsequently determine how those parameters impact patient quality of life (QOL). To achieve these objectives, the PI has assembled a multidisciplinary research team with a proven track record in the field, a novel set of established analytical tools, and the largest collection of single ventricle anatomy and flow data in the world. These assets will be utilized through the following synergistic approach: (1) we will perform a longitudinal analysis of TCPC hemodynamics and ventricular function;(2) we will compare the dynamics of the single ventricle and TCPC between rest and exercise using a CMR exercise protocol;and (3) we will conduct a cross-sectional assessment of patient QOL to quantify clinical outcomes, relate them to the measured hemodynamic and functional parameters, and determine which parameters are critical determinants and predictors of QOL. The novel components of this approach include the use of a CMR-compatible bike to obtain patient hemodynamic and function data under both resting and exercise conditions;the systematic quantification of TCPC hemodynamic (e.g. power loss) and cardiovascular function at rest and exercise in a cross-sectional study of over 150 patients;and the characterization of their temporal evolution in a longitudinal study. Correlation of these surrogates to quality of life measures will identify the strongest outcome predictors to be used for patient diagnosis. In parallel, combining these predictors with the simple mechanistic approaches will point to the cause of the deteriorating patient outcome. This will in turn help design improved surgical and clinical management strategies.

Public Health Relevance

This grant investigates the relationship between Fontan hemodynamics and ventricular function in patients born with single-ventricle heart defects. These surrogates will subsequently be correlated to quality of life measures to identify the strongest outcome predictors to be used for patient diagnosis. Understanding these interconnections will provide the means to develop optimal medical strategies to improve those outcomes.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL098252-04
Application #
8424979
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Burns, Kristin
Project Start
2010-02-01
Project End
2015-01-31
Budget Start
2013-02-01
Budget End
2015-01-31
Support Year
4
Fiscal Year
2013
Total Cost
$692,223
Indirect Cost
$103,871
Name
Georgia Institute of Technology
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
097394084
City
Atlanta
State
GA
Country
United States
Zip Code
30332
Wei, Zhenglun Alan; Tree, Michael; Trusty, Phillip M et al. (2018) The Advantages of Viscous Dissipation Rate over Simplified Power Loss as a Fontan Hemodynamic Metric. Ann Biomed Eng 46:404-416
Tree, Michael; Wei, Zhenglun Alan; Trusty, Phillip M et al. (2018) Using a Novel In Vitro Fontan Model and Condition-Specific Real-Time MRI Data to Examine Hemodynamic Effects of Respiration and Exercise. Ann Biomed Eng 46:135-147
Avitabile, Catherine M; Goldberg, David J; Leonard, Mary B et al. (2018) Leg lean mass correlates with exercise systemic output in young Fontan patients. Heart 104:680-684
Trusty, Phillip M; Slesnick, Timothy C; Wei, Zhenglun Alan et al. (2018) Fontan Surgical Planning: Previous Accomplishments, Current Challenges, and Future Directions. J Cardiovasc Transl Res 11:133-144
Wei, Zhenglun Alan; Trusty, Phillip M; Tree, Mike et al. (2017) Can time-averaged flow boundary conditions be used to meet the clinical timeline for Fontan surgical planning? J Biomech 50:172-179
Wei, Zhenglun; Whitehead, Kevin K; Khiabani, Reza H et al. (2016) Respiratory Effects on Fontan Circulation During Rest and Exercise Using Real-Time Cardiac Magnetic Resonance Imaging. Ann Thorac Surg 101:1818-25
Vallecilla, Carolina; Khiabani, Reza H; Trusty, Phillip et al. (2015) Exercise capacity in the Bidirectional Glenn physiology: Coupling cardiac index, ventricular function and oxygen extraction ratio. J Biomech 48:1997-2004
Haggerty, Christopher M; Whitehead, Kevin K; Bethel, James et al. (2015) Relationship of single ventricle filling and preload to total cavopulmonary connection hemodynamics. Ann Thorac Surg 99:911-7
Khiabani, Reza H; Whitehead, Kevin K; Han, David et al. (2015) Exercise capacity in single-ventricle patients after Fontan correlates with haemodynamic energy loss in TCPC. Heart 101:139-43
Restrepo, Maria; Luffel, Mark; Sebring, Jake et al. (2015) Surgical planning of the total cavopulmonary connection: robustness analysis. Ann Biomed Eng 43:1321-34

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