Mechanisms of Age-related Diastolic Dysfunction in Human

描述（由申请人提供）：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功能障碍而不是收缩功能障碍，尤其是在老年人中。 舒张性心力衰竭的发病机制尚不清楚。 人类的正常衰老伴随着左心室舒张早期充盈率的急剧和持续下降，原因不明，这可能在老年人CHF的易感性中起作用。 虽然这些充盈变化通常归因于与年龄相关的左心室舒张速率下降，但最近的研究未能证明老年人等容压下降的显着减缓。 在这个项目中，我们测试了新的假设，该假设是由本实验室和其他实验室使用磁共振成像（MRI）标记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，这有助于减缓舒张早期充盈。 左心房收缩和舒张特性的完整定义需要构建压力-容积环。 由于进入左心房通常需要经房间隔导管插入术，因此在正常受试者中没有此类研究。 我们的研究现在有一个独特的患者人群;我们将通过记录被转诊接受卵圆孔未闭（PFO）经皮闭合术的个体的左心房压力容积环来研究心房特性。 这些患者需要左心房器械进行临床PFO闭合，并且他们通常具有正常的左心室和与年龄相适应的舒张期充盈。 这为研究洛杉矶房产提供了绝佳的机会。 最近转诊到约翰霍普金斯医院接受该手术的患者年龄在25岁至79岁之间，因此提供了研究年龄相关变化的机会。 这些压力容积环将在前负荷和变力性状态变化期间被记录。 它们将允许对左心房的收缩力、舒张弹性和刚度进行全面评价。 我们的研究结果将有助于阐明舒张功能障碍的机制，由年龄引起的。 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.