Our NIH grant support over the last four years has allowed us to characterize the stress/strain profile of patients referred for aortic valve replacement (AVR) for chronic severe aortic insufficiency (AI), both before and after successful AVR. Their abnormally elevated preoperative left ventricular (LV) end-systolic stress returned to normal after AVR. Although resting systolic strain was normal before surgery, the strain response to dobutamine was blunted - and neither was normal postoperatively - despite the fact that they were referred for surgery early in the course of their disease (minimally or asymptomatic). This suggests that 1) our clinically applicable, MRI-based stress/strain indices are sensitive enough to consistently detect abnormalities even in minimally or asymptomatic AI patients, and 2) our current recommendations for timing of referral for AVR in this patient subset are not adequate to completely recover these sensitive stress/strain indices of ventricular function. Our data at least partially explain the well-recognized, not-infrequent occurrence of progressive LV dysfunction and heart failure after seemingly successful AVR for chronic AI. We propose to further define the early stages of the natural history of chronic AI by applying our stress/strain indices to asymptomatic patients who are being followed on medical therapy early in the course of their chronic AI. MRI-based, three-dimensional left ventricular geometrical data sets will be combined with clinically-acquired systolic ventricular loading conditions and advanced finite element modeling techniques to construct and utilize accurate, patient-specific, systolic mathematical models of the heart. We propose to characterize left ventricular systolic stress-strain profiles of patients with isolated aortic insufficiency by defining and graphically displaying quantifiable regional and global, 3D left ventricular 1) end-systolic geometry; 2) end-diastolic geometry; 3) end-systolic stress; 4) systolic strain ( dobutamine); and 5) systolic stress/strain ratio. Follow-up studies will be correlated with onset of symptoms, plasma BNP levels, and referral for aortic valve replacement. If AVR is undertaken, the patients will be studied postoperatively to correlate very early preoperative indices with subsequent recovery of stress/strain indices.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL064869-05A1
Application #
6868327
Study Section
Bioengineering, Technology and Surgical Sciences Study Section (BTSS)
Program Officer
Evans, Frank
Project Start
2000-04-10
Project End
2010-01-31
Budget Start
2005-02-01
Budget End
2006-01-31
Support Year
5
Fiscal Year
2005
Total Cost
$344,250
Indirect Cost
Name
Washington University
Department
Surgery
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Lindman, Brian R; Liu, Qi; Cupps, Brian P et al. (2017) Heterogeneity of systolic dysfunction in patients with severe aortic stenosis and preserved ejection fraction. J Card Surg 32:454-461
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
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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