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2016 ; 44
(1
): 112-27
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Modeling Pathologies of Diastolic and Systolic Heart Failure
#MMPMID26043672
Genet M
; Lee LC
; Baillargeon B
; Guccione JM
; Kuhl E
Ann Biomed Eng
2016[Jan]; 44
(1
): 112-27
PMID26043672
show ga
Chronic heart failure is a medical condition that involves structural and
functional changes of the heart and a progressive reduction in cardiac output.
Heart failure is classified into two categories: diastolic heart failure, a
thickening of the ventricular wall associated with impaired filling; and systolic
heart failure, a dilation of the ventricles associated with reduced pump
function. In theory, the pathophysiology of heart failure is well understood. In
practice, however, heart failure is highly sensitive to cardiac microstructure,
geometry, and loading. This makes it virtually impossible to predict the time
line of heart failure for a diseased individual. Here we show that computational
modeling allows us to integrate knowledge from different scales to create an
individualized model for cardiac growth and remodeling during chronic heart
failure. Our model naturally connects molecular events of parallel and serial
sarcomere deposition with cellular phenomena of myofibrillogenesis and
sarcomerogenesis to whole organ function. Our simulations predict chronic
alterations in wall thickness, chamber size, and cardiac geometry, which agree
favorably with the clinical observations in patients with diastolic and systolic
heart failure. In contrast to existing single- or bi-ventricular models, our new
four-chamber model can also predict characteristic secondary effects including
papillary muscle dislocation, annular dilation, regurgitant flow, and outflow
obstruction. Our prototype study suggests that computational modeling provides a
patient-specific window into the progression of heart failure with a view towards
personalized treatment planning.
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