Mechanisms of Age-related Diastolic Dysfunction in Human

描述(申请人提供)：随着人口老龄化，充血性心力衰竭(CHF)的患病率持续上升。几乎一半的心力衰竭病例是由于舒张期功能障碍而不是收缩功能障碍，特别是在老年人。舒张性心力衰竭的发病机制目前知之甚少。人类的正常衰老伴随着左心室早期舒张期充盈率的急剧和无情的下降，原因不明，这可能在老年人易患CHF中起作用。虽然这些充盈变化通常被归因于与年龄相关的左心室松弛速度的下降，但最近的研究未能证明老年人等容压下降的显著放缓。在这个项目中，我们测试了这个新的假设，这个假设是由来自这个实验室和其他实验室的使用带有标记的磁共振成像(MRI)和超声心动图的研究提出的，即左心房(LA)的特性存在与年龄相关的变化，这是导致早期舒张期充盈减慢的原因之一。 完整定义LA的收缩和舒张期特性需要构建压力-体积环。在正常受试者中还没有这样的研究，因为进入左心房通常需要经过间隔导管术。一个独特的患者群体现在可以用于我们的研究；我们将通过记录经皮卵圆孔未闭(PFO)患者的LA压力容量环来研究心房的特性。这些患者需要左房内固定装置来关闭临床的PFO，他们通常有正常的左心室和与年龄相适应的舒张期充盈。这为研究LA的性质提供了绝佳的机会。最近转诊到约翰霍普金斯大学进行这项手术的患者年龄从25岁到79岁不等，因此提供了一个研究与年龄相关的变化的机会。 这些压力体积环将在预载荷和变力状态变化期间被记录下来。它们将允许全面评估LA的收缩能力、舒张期弹性和僵硬程度。我们的结果将有助于阐明年龄引起的舒张期功能障碍的机制。这可能会导致合理的新疗法的发展。

DESCRIPTION (provided by applicant): The prevalence of congestive heart failure (CHF) continues to rise as the population ages. Almost half of the cases of heart failure are due to diastolic rather than systolic dysfunction, especially in the elderly. The mechanisms underlying diastolic heart failure are poorly understood. Normal aging in humans is accompanied by a sharp and relentless decline in the rate of LV early diastolic filling, of uncertain cause, which may play a role in the predisposition of the elderly to CHF. While these filling changes are often attributed to an age-related decline in the rate of left ventricular relaxation, recent studies have failed to demonstrate a significant slowing of the isovolumic pressure fall in the elderly. In this project we test the new hypothesis, suggested by studies using magnetic resonance imaging (MRI) with tagging, and echocardiography, from this lab and others, that there are age-related changes in the properties of the left atrium (LA), which contribute to this slowed early diastolic filling. Full definition of LA systolic and diastolic properties requires the construction of pressure-volume loops. There have been no such studies in normal subjects, since entering the left atrium typically requires transseptal catheterization. A unique patient population is now available for our investigation; we will study atrial properties by recording LA pressure volume loops in individuals who are referred for percutaneous closure of a patent foramen ovale (PFO). These patients require left atrial instrumentation for the clinical PFO closure, and they typically have a normal left ventricle and age-appropriate diastolic filling. This provides the perfect opportunity for studying LA properties. Patients recently referred to Johns Hopkins for this procedure range in age from 25 to 79, and therefore present an opportunity to study age-related changes. These pressure volume loops will be recorded during variation of preload and inotropic state. They will allow full evaluation of the LA for systolic contractility, and for diastolic elasticity and stiffness. Our results will help clarify the mechanisms of diastolic dysfunction induced by age. This may lead to the development of rational new therapies.