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.
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