Blood flow generation by the heart is the result of synchronized electromechanical myocardial events and fluid dynamics processes. Interactions between blood flow and the myocardium elicit the continuous remodeling of the heart, leading to flow patterns that minimize energy losses. The flow pattern in the normal left ventricle consists of a large diastolic vortex that channels the transit of blood towards the outflow tract. In a failing left ventricle, progressive adverse remodeling leads to abnormal flow patterns that are less efficient in channeling blood transit, and which may contribute further to the progression of heart failure. Thus, a deeper understanding of blood flow dynamics in normal and diseased left ventricles may provide insight on the pathophysiology of heart failure, leading to earlier diagnosis and improved treatment strategies of this syndrome. Recent years have witnessed a surge of interest in studying the role of flow patterns in blood transport inside the left ventricle. Despite significant advances, we still understand poorly how the fluid dynamical processes are synchronized with the electromechanical events to generate blood flow. Our preliminary studies suggest that the position and properties of diastolic vortices, and consequently, their ability to channel blood transit through the LV, are related to the timing of the myocardial events of the cycle. The goal of this research is to understand the dependence of the time evolution of the diastolic vortices on the duration of the left-ventricular filling phases, and to determine how this dependence affects blood flow transport and global ventricular function. In order to carry out the proposed research we have assembled an interdisciplinary team of investigators with complementary expertise ranging from cardiology, echocardiography and magnetic resonance imaging, to fluid dynamics, computational mechanics and image processing. We will validate and apply a novel echocardiographic modality to measure two-dimensional bi-directional time-resolved flow maps in the left ventricle in a group of patients undergoing cardiac resynchronization therapy at the UCSD Medical Center. We will use these measurements to determine the time evolution of diastolic vortices in these patients for different AV and VV delays, and characterize how these delays affect the transit of blood inside the left ventricle. We postulate that better knowledge of this dependence will increase our understanding of the benefits of cardiac resynchronization therapy. It will also improve current protocols for VV and AV optimization by improving patient selection and enabling LV contraction to take place under the most favorable hemodynamic conditions.

Public Health Relevance

The proposed study aims to develop engineering technologies to non-invasively measure blood transport inside the left ventricle of patients undergoing cardiac resynchronization therapy, with the overarching goal of improving patient selection and optimization of this therapy.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21HL108268-01
Application #
8096140
Study Section
Special Emphasis Panel (ZRG1-SBIB-J (80))
Program Officer
Baldwin, Tim
Project Start
2011-05-15
Project End
2013-03-31
Budget Start
2011-05-15
Budget End
2012-03-31
Support Year
1
Fiscal Year
2011
Total Cost
$229,513
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
Rossini, Lorenzo; Martinez-Legazpi, Pablo; Vu, Vi et al. (2016) A clinical method for mapping and quantifying blood stasis in the left ventricle. J Biomech 49:2152-2161
Yotti, Raquel; Bermejo, Javier; Gutiérrez-Ibañes, Enrique et al. (2015) Systemic vascular load in calcific degenerative aortic valve stenosis: insight from percutaneous valve replacement. J Am Coll Cardiol 65:423-33
Banerjee, Indroneal; Carrion, Katrina; Serrano, Ricardo et al. (2015) Cyclic stretch of embryonic cardiomyocytes increases proliferation, growth, and expression while repressing Tgf-? signaling. J Mol Cell Cardiol 79:133-44
Pérez Del Villar, Candelas; Bermejo, Javier; Rodríguez-Pérez, Daniel et al. (2015) The role of elastic restoring forces in right-ventricular filling. Cardiovasc Res 107:45-55
Bermejo, Javier; Benito, Yolanda; Alhama, Marta et al. (2014) Intraventricular vortex properties in nonischemic dilated cardiomyopathy. Am J Physiol Heart Circ Physiol 306:H718-29
Wong, K; Samaroo, G; Ling, I et al. (2014) Intraventricular flow patterns and stasis in the LVAD-assisted heart. J Biomech 47:1485-94
Yotti, Raquel; Bermejo, Javier; Benito, Yolanda et al. (2014) Validation of noninvasive indices of global systolic function in patients with normal and abnormal loading conditions: a simultaneous echocardiography pressure-volume catheterization study. Circ Cardiovasc Imaging 7:164-72
Martínez-Legazpi, Pablo; Bermejo, Javier; Benito, Yolanda et al. (2014) Contribution of the diastolic vortex ring to left ventricular filling. J Am Coll Cardiol 64:1711-21
Bermejo, Javier; Yotti, Raquel; Pérez del Villar, Candelas et al. (2013) Diastolic chamber properties of the left ventricle assessed by global fitting of pressure-volume data: improving the gold standard of diastolic function. J Appl Physiol (1985) 115:556-68
Hendabadi, Sahar; Bermejo, Javier; Benito, Yolanda et al. (2013) Topology of blood transport in the human left ventricle by novel processing of Doppler echocardiography. Ann Biomed Eng 41:2603-16

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