Clinical outcomes are worse in ischemic cardiomyopathy patients when cardiac surgical or catheter-based revascularization interventions are directed at coronary arteries that serve non-viable myocardium. Therefore improved accuracy in determination of regional myocardial viability will result in improved accuracy of direction of revascularization procedures and improved patient outcomes. MRI-based myocardial systolic strain analysis utilizes systolic tag line grid point displacements obtained from MRI radiofrequency tissue tagging to generate highly accurate 3D left ventricular (LV) strain maps. During the previous funding period, minimum principal strain vector analysis was developed into a clinically applicable parameter of myocardial viability and combined with two other advanced strain parameters into an MRI-based multiparametric strain analysis. Our preliminary data suggest that this analysis may have unparalleled accuracy in regional and transmural characterization of myocardial viability. The combination of three strain indices with widely variable ranges is made possible by relating each patient-specific strain parameter value at each of 15,300 grid points in the LV to the """"""""normal"""""""" value of that parameter at that corresponding point in the LV. The normal value (average SD) for each strain parameter at each of 15,300 LV grid points was generated from a normal human strain database established by our laboratory (complete MRI-based multiparametric strain analysis data from >60 normal human subjects). Objectives and Specific Aims. The goals of this investigation are to determine the efficacy of MRI-based multiparametric strain analysis in characterizing regional myocardial viability in the clinical setting and to prospectively compare this efficacy to that of currently utilized clinical standard viability detection modalities. Research Design and Methods. We will use MRI-based multiparametric strain analysis dobutamine provocation to study patients with akinetic LV regions that are served by atherosclerotic coronary arteries upon which surgical or catheter-based intervention is planned. Two months following the planned revascularization, echocardiography will be directed at the target LV region. An improvement in the target regional wall function can only occur in a viable region while no improvement in function indicates non-viability. This supplies a clinically relevant """"""""gold standard"""""""" against which MRI-based multiparametric strain analysis, as well as the current clinical standards (thallium SPECT, PET and dobutamine echocardiography), can be prospectively tested to determine sensitivity and specificity in the identification of non-viable myocardium in six standardized regions of the left ventricle. Single strain parameters will also be tested against the multiparametric analysis in accuracy of clinical viability determination. Pre-revascularization dobutamine provocation will test for recruitment of residual contractile function in akinetic LV regions (hibernating myocardium).

Public Health Relevance

Atherosclerotic coronary artery disease is the largest single killer of Americans and the most complex subset of these patients have decreased heart function because of the blockage in their coronary arteries. Coronary bypass surgery and coronary stenting are risky and expensive in these patients and offer no benefit if the decrease in heart function is secondary to heart muscle death (myocardial infarction). We will test the hypothesis that our MRI-based multiparametric strain analysis can determine whether the heart muscle is alive or dead more accurately than any other currently available test, and therefore more accurately direct which patients should undergo risky and expensive coronary bypass surgery or coronary stenting.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL069967-06
Application #
7851339
Study Section
Bioengineering, Technology and Surgical Sciences Study Section (BTSS)
Program Officer
Adhikari, Bishow B
Project Start
2002-04-01
Project End
2011-06-30
Budget Start
2010-07-01
Budget End
2011-06-30
Support Year
6
Fiscal Year
2010
Total Cost
$441,849
Indirect Cost
Name
Washington University
Department
Surgery
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Henn, Matthew C; Cupps, Brian P; Kar, Julia et al. (2015) Quantifying ""normalized"" regional left ventricular contractile function in ischemic coronary artery disease. J Thorac Cardiovasc Surg 150:240-6
Henn, Matthew C; Lawrance, Christopher P; Kar, Julia et al. (2015) Dilated Cardiomyopathy: Normalized Multiparametric Myocardial Strain Predicts Contractile Recovery. Ann Thorac Surg 100:1284-91
Maniar, Hersh S; Brady, Beckah D; Lee, Urvi et al. (2014) Early left ventricular regional contractile impairment in chronic mitral regurgitation occurs in a consistent, heterogeneous pattern. J Thorac Cardiovasc Surg 148:1694-9
Brady, Beckah D; Knutsen, Andrew K; Ma, Ningning et al. (2012) MRI-based multiparametric strain analysis predicts contractile recovery after aortic valve replacement for aortic insufficiency. J Card Surg 27:415-22
Knutsen, Andrew K; Ma, Ningning; Taggar, Ajay K et al. (2012) Heterogeneous distribution of left ventricular contractile injury in chronic aortic insufficiency. Ann Thorac Surg 93:1121-7
Lawton, Jennifer S; Cupps, Brian P; Knutsen, Andrew K et al. (2011) Magnetic resonance imaging detects significant sex differences in human myocardial strain. Biomed Eng Online 10:76
Singh, Gautam K; Cupps, Brian; Pasque, Michael et al. (2010) Accuracy and reproducibility of strain by speckle tracking in pediatric subjects with normal heart and single ventricular physiology: a two-dimensional speckle-tracking echocardiography and magnetic resonance imaging correlative study. J Am Soc Echocardiogr 23:1143-52
Cupps, Brian P; Taggar, Ajay K; Reynolds, Lina M et al. (2010) Regional myocardial contractile function: multiparametric strain mapping. Interact Cardiovasc Thorac Surg 10:953-7
Joseph, Susan; Moazami, Nader; Cupps, Brian P et al. (2009) Magnetic resonance imaging-based multiparametric systolic strain analysis and regional contractile heterogeneity in patients with dilated cardiomyopathy. J Heart Lung Transplant 28:388-94
Cupps, Brian P; Bree, Douglas R; Wollmuth, Jason R et al. (2008) Myocardial viability mapping by magnetic resonance-based multiparametric systolic strain analysis. Ann Thorac Surg 86:1546-53

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