Left Ventricular Remodeling in Aortic Insufficiency

主动脉瓣关闭不全的左心室重构

• 批准号: 7010745
• 负责人: MICHAEL K PASQUE
• 金额: $ 33.62万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-10 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7010745
• 关键词: aortic valve; aortic valve insufficiency; biomechanics; cardiovascular surgery; clinical research; dobutamine; heart catheterization; heart contraction; heart ventricle; human subject; human therapy evaluation; longitudinal human study; magnetic resonance imaging; mathematical model; medical implant science; muscle stress; myocardium; pathologic process; patient oriented research; postoperative state; preoperative state; prognosis; prosthetic heart valve

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.

在过去四年中，我们的NIH拨款支持使我们能够描述因慢性重度主动脉瓣关闭不全（AI）而接受主动脉瓣置换术（AVR）的患者在成功AVR前后的应力/应变特征。术前异常升高的左心室（LV）收缩末期应力在AVR后恢复正常。尽管术前静息收缩期应变正常，但对多巴酚丁胺的应变反应迟钝-术后也不正常-尽管他们在疾病早期（最小或无症状）被转诊手术。这表明：1）我们的临床适用、基于MRI的应力/应变指数足够敏感，即使在最低程度或无症状AI患者中也能持续检测到异常，2）我们目前关于该患者亚组中AVR转诊时间的建议不足以完全恢复心室功能的这些敏感应力/应变指数。我们的数据至少部分解释了在看似成功的AVR治疗慢性AI后，公认的、并非罕见的进行性LV功能障碍和心力衰竭的发生。 我们建议通过将我们的压力/应变指数应用于在慢性AI早期接受药物治疗的无症状患者，进一步定义慢性AI自然史的早期阶段。基于MRI的三维左心室几何数据集将与临床采集的收缩期心室负荷条件和先进的有限元建模技术相结合，以构建和利用准确的、患者特异性的心脏收缩数学模型。我们建议通过定义和图形显示可量化的局部和全局3D左心室1）收缩末期几何形状; 2）舒张末期几何形状; 3）收缩末期应力; 4）收缩应变（多巴酚丁胺）;和5）收缩应力/应变比来表征孤立性主动脉瓣关闭不全患者的左心室收缩应力-应变曲线。随访研究将与症状发作、血浆BNP水平和主动脉瓣置换转诊相关。如果进行主动脉瓣置换术，将在术后对患者进行研究，以将非常早期的术前指数与随后的应力/应变指数恢复相关联。