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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Burns, Kristin
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Georgia Institute of Technology
Engineering (All Types)
Schools of Engineering
United States
Zip Code
Avitabile, Catherine M; Leonard, Mary B; Zemel, Babette S et al. (2014) Lean mass deficits, vitamin D status and exercise capacity in children and young adults after Fontan palliation. Heart 100:1702-7
Tang, Elaine; Restrepo, Maria; Haggerty, Christopher M et al. (2014) Geometric characterization of patient-specific total cavopulmonary connections and its relationship to hemodynamics. JACC Cardiovasc Imaging 7:215-24
Restrepo, Maria; Mirabella, Lucia; Tang, Elaine et al. (2014) Fontan pathway growth: a quantitative evaluation of lateral tunnel and extracardiac cavopulmonary connections using serial cardiac magnetic resonance. Ann Thorac Surg 97:916-22
Vallecilla, Carolina; Khiabani, Reza H; Sandoval, NĂ©stor et al. (2014) Effect of high altitude exposure on the hemodynamics of the bidirectional Glenn physiology: modeling incremented pulmonary vascular resistance and heart rate. J Biomech 47:1846-52
Haggerty, Christopher M; Restrepo, Maria; Tang, Elaine et al. (2014) Fontan hemodynamics from 100 patient-specific cardiac magnetic resonance studies: a computational fluid dynamics analysis. J Thorac Cardiovasc Surg 148:1481-9
Desai, Kalpi; Haggerty, Christopher M; Kanter, Kirk R et al. (2013) Haemodynamic comparison of a novel flow-divider Optiflo geometry and a traditional total cavopulmonary connection. Interact Cardiovasc Thorac Surg 17:1-7
Mirabella, Lucia; Haggerty, Christopher M; Passerini, Tiziano et al. (2013) Treatment planning for a TCPC test case: a numerical investigation under rigid and moving wall assumptions. Int J Numer Method Biomed Eng 29:197-216
Tang, Elaine; Haggerty, Christopher M; Khiabani, Reza H et al. (2013) Numerical and experimental investigation of pulsatile hemodynamics in the total cavopulmonary connection. J Biomech 46:373-82
de Zelicourt, Diane A; Haggerty, Christopher M; Sundareswaran, Kartik S et al. (2011) Individualized computer-based surgical planning to address pulmonary arteriovenous malformations in patients with a single ventricle with an interrupted inferior vena cava and azygous continuation. J Thorac Cardiovasc Surg 141:1170-7
Dasi, Lakshmi P; Whitehead, Kevin; Pekkan, Kerem et al. (2011) Pulmonary hepatic flow distribution in total cavopulmonary connections: extracardiac versus intracardiac. J Thorac Cardiovasc Surg 141:207-14