Pediatric heart failure cost the United States an estimated $2 billion in 2006 and is increasing in prevalence and cost despite hospital mortality unfortunately remaining constant at 7%. The big-picture goal of our current research program is to attempt to address this problem by adapting a relatively new, highly successful therapy for adult heart failure called cardiac resynchronization therapy (CRT), into a treatment option for children with heart failure. The most critical knowledge gap is identifying which children are most likely to benefit from CRT. The current application addresses this challenge in a population of patients with a common, serious congenital heart defect known as tetralogy of Fallot (TOF). Patients born with tetralogy of Fallot (TOF), the most common cyanotic congenital heart defect, currently undergo surgical repair as children but later develop heart failure as adults. This research will investigate whether the surgical repair predisposes these patients to uncoordinated contraction in the heart as a result of disruption of electrical conduction pathways which occurs during surgery. If this uncoordination (or """"""""dyssynchrony"""""""") proves to be a significant factor, it can be treated with CRT, thus yielding a new treatment for patients with heart failure due to TOF. We are able to explore the role of dyssynchrony in these patients because we recently developed unique methodology and software to derive indices of dyssynchrony in the heart from standard magnetic resonance images (MRI). We hypothesize that patients with surgically repaired TOF suffer from dyssynchronous contraction in the heart and that dyssynchrony contributes to the development of heart failure and eventual mortality in these patients. We propose to test our hypotheses with the following specific aims: 1) evaluate whether patients with repaired TOF suffer from dyssynchrony when compared to normal subjects 2) evaluate whether dyssynchrony leads to worsening ventricular function over time in patients with repaired TOF and 3) determine whether dyssynchrony is related to mortality in patients with repaired TOF. Completion of this application should therefore improve the health and care of patients with repaired TOF through identifying potentially lifesaving treatment options for them. Additionally, our approach can be used in future work to explore the role of dyssynchrony in patients with other diseases associated with electrical conduction abnormalities such as dilated cardiomyopathy, thus furthering our long-term goal to translate cardiac resynchronization therapy into a treatment option to improve the health of children with heart failure.

Public Health Relevance

Pediatric heart failure cost the United States an estimated $2 billion in 2006 and is increasing in prevalence and cost with no corresponding improvement in hospital mortality. The big-picture goal of our research program is to attempt to address this problem by adapting a relatively new, highly successful therapy for adult heart failure called cardiac resynchronization therapy, into a treatment option to improve the health of children with heart failure.

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
Early Independence Award (DP5)
Project #
5DP5OD012132-03
Application #
8720572
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Basavappa, Ravi
Project Start
2012-09-25
Project End
2017-08-31
Budget Start
2014-09-01
Budget End
2015-08-31
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Kentucky
Department
Pediatrics
Type
Schools of Medicine
DUNS #
City
Lexington
State
KY
Country
United States
Zip Code
40506
Hamlet, Sean M; Haggerty, Christopher M; Suever, Jonathan D et al. (2016) Optimal configuration of respiratory navigator gating for the quantification of left ventricular strain using spiral cine displacement encoding with stimulated echoes (DENSE) MRI. J Magn Reson Imaging :
Hamlet, Sean M; Haggerty, Christopher M; Suever, Jonathan D et al. (2016) An interactive videogame designed to improve respiratory navigator efficiency in children undergoing cardiovascular magnetic resonance. J Cardiovasc Magn Reson 18:54
Jing, Linyuan; Wehner, Gregory J; Suever, Jonathan D et al. (2016) Left and right ventricular dyssynchrony and strains from cardiovascular magnetic resonance feature tracking do not predict deterioration of ventricular function in patients with repaired tetralogy of Fallot. J Cardiovasc Magn Reson 18:49
Wehner, Gregory J; Suever, Jonathan D; Haggerty, Christopher M et al. (2015) Validation of in vivo 2D displacements from spiral cine DENSE at 3T. J Cardiovasc Magn Reson 17:5
Wehner, Gregory J; Grabau, Jonathan D; Suever, Jonathan D et al. (2015) 2D cine DENSE with low encoding frequencies accurately quantifies cardiac mechanics with improved image characteristics. J Cardiovasc Magn Reson 17:93
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Haggerty, Christopher M; Kramer, Sage P; Skrinjar, Oskar et al. (2014) Quantification of left ventricular volumes, mass, and ejection fraction using cine displacement encoding with stimulated echoes (DENSE) MRI. J Magn Reson Imaging 40:398-406
Jing, Linyuan; Haggerty, Christopher M; Suever, Jonathan D et al. (2014) Patients with repaired tetralogy of Fallot suffer from intra- and inter-ventricular cardiac dyssynchrony: a cardiac magnetic resonance study. Eur Heart J Cardiovasc Imaging 15:1333-43
Suever, Jonathan D; Wehner, Gregory J; Haggerty, Christopher M et al. (2014) Simplified post processing of cine DENSE cardiovascular magnetic resonance for quantification of cardiac mechanics. J Cardiovasc Magn Reson 16:94
Haggerty, Christopher M; Kramer, Sage P; Binkley, Cassi M et al. (2013) Reproducibility of cine displacement encoding with stimulated echoes (DENSE) cardiovascular magnetic resonance for measuring left ventricular strains, torsion, and synchrony in mice. J Cardiovasc Magn Reson 15:71

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