Left Ventricular Remodeling in Aortic Insufficiency

在过去四年中，我们为NIH提供的资助使我们能够确定因慢性重度主动脉瓣关闭不全(AI)而行主动脉瓣置换术(AVR)的患者在AVR成功前后的应力/应变特征。术前异常升高的左心室收缩末期应力在AVR后恢复正常。尽管手术前静息收缩张力是正常的，但对多巴酚丁胺的紧张反应是迟钝的--手术后也不是正常的--尽管他们在病程的早期(最小或无症状)被转介进行手术。这表明，1)我们基于MRI的临床适用的应力/应变指数足够敏感，即使在轻微或无症状的AI患者中也能持续检测到异常；2)我们目前对这一患者亚组的AVR转诊时间的建议不足以完全恢复这些敏感的心功能应力/应变指数。我们的数据至少部分解释了公认的、并不罕见的进行性左心功能障碍和心力衰竭的发生，在似乎成功地治疗慢性AI的AVR之后。 我们建议通过将我们的压力/应变指数应用于在慢性AI病程早期接受药物治疗的无症状患者来进一步定义慢性AI自然历史的早期阶段。基于磁共振成像的三维左心室几何数据集将与临床获得的收缩心室负荷状况和先进的有限元建模技术相结合，以构建和利用准确的、患者特定的心脏收缩数学模型。我们建议通过定义和图形化显示可量化的局部和整体、三维左心室收缩末期几何形状、2)舒张末几何形状、3)收缩末期应力、4)收缩期应变(多巴酚丁胺)和5)收缩期应力/应变比来表征孤立性主动脉瓣关闭不全患者的左室收缩应力-应变曲线。后续研究将与症状的出现、血浆BNP水平和主动脉瓣置换术的转诊相关。如果进行了AVR，将在术后对患者进行研究，以确定非常早期的术前指标与随后的应力/应变指标的恢复之间的关系。

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.