Understanding mechanisms of Fontan failure and key predictors for patient outcome

Summary

Principal Investigator: Ajit P Yoganathan
Abstract: DESCRIPTION (provided by applicant): 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.
Funding Period: 2010-02-01 - 2015-01-31
more information: NIH RePORT

Top Publications

  1. pmc Pulmonary hepatic flow distribution in total cavopulmonary connections: extracardiac versus intracardiac
    Lakshmi P Dasi
    Department of Mechanical Engineering and School of Biomedical Engineering, Colorado State University, Fort Collins, Colo, USA
    J Thorac Cardiovasc Surg 141:207-14. 2011
  2. pmc Geometric characterization of patient-specific total cavopulmonary connections and its relationship to hemodynamics
    Elaine Tang
    School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia
    JACC Cardiovasc Imaging 7:215-24. 2014
  3. pmc Fontan pathway growth: a quantitative evaluation of lateral tunnel and extracardiac cavopulmonary connections using serial cardiac magnetic resonance
    Maria Restrepo
    The Wallace H Coulter Department of Biomedical Engineering at Georgia Institute of Technology and Emory University, Atlanta, Georgia
    Ann Thorac Surg 97:916-22. 2014
  4. ncbi Magnetic resonance imaging-guided surgical design: can we optimise the Fontan operation?
    Christopher M Haggerty
    1 The Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, United States of America
    Cardiol Young 23:818-23. 2013
  5. pmc Haemodynamic comparison of a novel flow-divider Optiflo geometry and a traditional total cavopulmonary connection
    Kalpi Desai
    Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA
    Interact Cardiovasc Thorac Surg 17:1-7. 2013
  6. ncbi Treatment planning for a TCPC test case: a numerical investigation under rigid and moving wall assumptions
    Lucia Mirabella
    Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA
    Int j numer method biomed eng 29:197-216. 2013
  7. pmc Numerical and experimental investigation of pulsatile hemodynamics in the total cavopulmonary connection
    Elaine Tang
    School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, United States
    J Biomech 46:373-82. 2013
  8. pmc Effect of flow pulsatility on modeling the hemodynamics in the total cavopulmonary connection
    Reza H Khiabani
    Wallace H Coulter School of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, 30332 0535, USA
    J Biomech 45:2376-81. 2012
  9. pmc Comparing pre- and post-operative Fontan hemodynamic simulations: implications for the reliability of surgical planning
    Christopher M Haggerty
    Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Drive, Atlanta, GA 30332, USA
    Ann Biomed Eng 40:2639-51. 2012
  10. pmc Simulating hemodynamics of the Fontan Y-graft based on patient-specific in vivo connections
    Christopher M Haggerty
    Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA
    J Thorac Cardiovasc Surg 145:663-70. 2013

Research Grants

  1. CARDIOVASCULAR DYNAMICS AND THEIR CONTROL
    John E Hall; Fiscal Year: 2013

Detail Information

Publications13

  1. pmc Pulmonary hepatic flow distribution in total cavopulmonary connections: extracardiac versus intracardiac
    Lakshmi P Dasi
    Department of Mechanical Engineering and School of Biomedical Engineering, Colorado State University, Fort Collins, Colo, USA
    J Thorac Cardiovasc Surg 141:207-14. 2011
    ..We studied the effect of total cavopulmonary connection geometry and the effect of increased cardiac output on distribution of inferior vena caval return to the lungs...
  2. pmc Geometric characterization of patient-specific total cavopulmonary connections and its relationship to hemodynamics
    Elaine Tang
    School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia
    JACC Cardiovasc Imaging 7:215-24. 2014
    ..Hepatic flow distribution correlated with caval offset, pulmonary flow distribution, and the angle between FP and SVC. These correlations can have important implications for future connection design and patient follow-up. ..
  3. pmc Fontan pathway growth: a quantitative evaluation of lateral tunnel and extracardiac cavopulmonary connections using serial cardiac magnetic resonance
    Maria Restrepo
    The Wallace H Coulter Department of Biomedical Engineering at Georgia Institute of Technology and Emory University, Atlanta, Georgia
    Ann Thorac Surg 97:916-22. 2014
    ..The LT is formed partially by atrial wall and is assumed to have growth potential, but the extent and nature of LT pathway growth have not been well characterized. A quantitative analysis was performed to evaluate this issue...
  4. ncbi Magnetic resonance imaging-guided surgical design: can we optimise the Fontan operation?
    Christopher M Haggerty
    1 The Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, United States of America
    Cardiol Young 23:818-23. 2013
    ..This review provides a brief overview of these methods, presents preliminary results of their clinical usage, and offers insights into its potential future directions...
  5. pmc Haemodynamic comparison of a novel flow-divider Optiflo geometry and a traditional total cavopulmonary connection
    Kalpi Desai
    Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA
    Interact Cardiovasc Thorac Surg 17:1-7. 2013
    ..The use of a bifurcated graft as the Fontan baffle (i.e. the 'Optiflo') has previously been proposed on the basis of theoretically improved flow efficiency; however, anatomical constraints may limit its effectiveness in some patients...
  6. ncbi Treatment planning for a TCPC test case: a numerical investigation under rigid and moving wall assumptions
    Lucia Mirabella
    Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA
    Int j numer method biomed eng 29:197-216. 2013
    ..The largest differences between rigid and moving wall models are observed in measures of energetic efficiency of TCPC as well as in hepatic flow distribution and transit time of seeded particles through the connection...
  7. pmc Numerical and experimental investigation of pulsatile hemodynamics in the total cavopulmonary connection
    Elaine Tang
    School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, United States
    J Biomech 46:373-82. 2013
    ..The results demonstrated the complexity of the pulsatile TCPC flow fields and the validity of the numerical approach in simulating pulsatile TCPC flow dynamics in both idealized and complex patient specific models...
  8. pmc Effect of flow pulsatility on modeling the hemodynamics in the total cavopulmonary connection
    Reza H Khiabani
    Wallace H Coulter School of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, 30332 0535, USA
    J Biomech 45:2376-81. 2012
    ..In addition, when wPI<50, the relative error was less than 20%. A correlation was introduced to relate wPI to the relative error in predicting the flow metrics with non-pulsatile flow conditions...
  9. pmc Comparing pre- and post-operative Fontan hemodynamic simulations: implications for the reliability of surgical planning
    Christopher M Haggerty
    Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Drive, Atlanta, GA 30332, USA
    Ann Biomed Eng 40:2639-51. 2012
    ..These results demonstrate that surgical planning can be a useful tool for single ventricle cardiothoracic surgery with the ability to deliver significant clinical impact...
  10. pmc Simulating hemodynamics of the Fontan Y-graft based on patient-specific in vivo connections
    Christopher M Haggerty
    Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA
    J Thorac Cardiovasc Surg 145:663-70. 2013
    ..This study conducted numerical simulations to evaluate this hypothesis using postoperative data from 5 patients...
  11. pmc 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
    Diane A de ZĂ©licourt
    Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332 0535, USA
    J Thorac Cardiovasc Surg 141:1170-7. 2011
    ..The current study combines virtual surgery and numeric simulations to identify potential surgical strategies for patients with an interrupted inferior vena cava...
  12. ncbi Effect of high altitude exposure on the hemodynamics of the bidirectional Glenn physiology: modeling incremented pulmonary vascular resistance and heart rate
    Carolina Vallecilla
    Group of Biomedical Engineering, Universidad de Los Andes, Bogota, Colombia
    J Biomech 47:1846-52. 2014
    ..The presented mathematical model provides a framework to estimate the hemodynamic performance of BDG patients at different PVR increments. ..

Research Grants30

  1. CARDIOVASCULAR DYNAMICS AND THEIR CONTROL
    John E Hall; Fiscal Year: 2013
    ..End of Abstract) ..