Cardiac malformations are the most common type of birth defect. Improvements in the management of complex congenital heart disease have resulted in >90% of those born with congenital heart disease now able to survive into early adulthood. In the U.S. alone, there are more adults with congenital heart disease (~1 million individuals) than children. Tetralogy of Fallot (TOF) is the commonest cyanotic congenital heart lesion, and there is now a large and growing population of adults with TOF. The surgical repairs these patients require early in life often lead to residual pulmonary regurgitation that can cause eventual right ventricular enlargement and dysfunction, and pre-dispose to heart failure, arrhythmias, and sudden death. In the course of clinical management, deciding whether and when to perform pulmonary valve replacement to prevent ventricular decompensation is therefore critical and warrants quantifiable means of assessment. The goal of this project is to expand the current Congenital Heart Disease study of the Cardiac Atlas Project database to include a large cohort of patient with post-operative TOF, and to use the patient cardiac magnetic resonance (CMR) exams and other clinical data to derive statistical atlases of shape, biomechanics and electrical dyssynchrony. These atlases will be used to test hypotheses and discover clinical biomarkers that predict outcomes of pulmonary valve replacement based on variations in ventricular shape, mechanical properties and electromechanical dyssynchrony.
The specific aims are: (1) To use disease-specific statistical shape atlases derived from non-invasive imaging exams of patients with TOF to test the hypothesis that specific biventricular shape modes can discriminate patients by their degree of recovery of ventricular function and their extent of reverse cardiac remodeling after valve replacement; (2) To use finite element models of biventricular biomechanics to investigate the extent to which clinically significant relationships between ventricular shape modes and improvements in ventricular function post-valve repair are due to shape alone vs. differences in myocardial material properties; and (3) To determine how dyssynchronous electrical activation patterns that give rise to heterogeneous regional contraction affect hemodynamic improvement and reverse ventricular remodeling after pulmonary valve replacement in TOF patients. This work will have a significant impact on the clinical management of congenital heart disease by providing: new insights into biomechanical alterations in post-operative TOF; new predictors of outcomes following pulmonary valve replacement; and a greatly expanded web-accessible database of CMR exams, models and statistical atlases to facilitate clinical research and training in congenital heart disease.

Public Health Relevance

Although surgical and other treatments for congenital heart disease have improved, there is a critical need for enhanced assessment and prediction of adverse conditions in these patients. This proposal will build on a web-accessible shape and biomechanical atlas of congenital heart disease, adding a large multi-center cohort of tetralogy of Fallot patients. This resource will help accelerate the translation of clinical and basic research into improved strategies for treating tetralogy patients with disease-specific care.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL121754-05
Application #
9818587
Study Section
Modeling and Analysis of Biological Systems Study Section (MABS)
Program Officer
Egerson, D'Andrea R
Project Start
2014-01-01
Project End
2024-06-30
Budget Start
2019-08-07
Budget End
2020-06-30
Support Year
5
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of California, San Diego
Department
Engineering (All Types)
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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