Left Ventricular Remodeling in Aortic Insufficiency

在过去的四年里，我们的NIH拨款支持使我们能够描述因慢性严重主动脉瓣不全（AI）而进行主动脉瓣置换术（AVR）的患者在成功进行AVR之前和之后的压力/应变特征。术前异常升高的左心室收缩末期压力在AVR后恢复正常。尽管手术前静息收缩应变正常，但对多巴酚丁胺的应变反应变钝了——手术后两者都不正常——尽管他们在病程早期（最低限度或无症状）就接受了手术。这表明1)我们临床适用的、基于mri的压力/应变指标足够敏感，即使在最小或无症状的AI患者中也能持续检测异常；2)我们目前对该患者亚群中AVR转诊时间的建议不足以完全恢复这些敏感的心室功能压力/应变指标。我们的数据至少部分地解释了在慢性AI的AVR看似成功后，进行性左室功能障碍和心力衰竭的发生率，这是公认的，并非罕见的。

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.