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.
| Hees, Paul S; Fleg, Jerome L; Mirza, Zulfiqar A et al. (2006) Effects of normal aging on left ventricular lusitropic, inotropic, and chronotropic responses to dobutamine. J Am Coll Cardiol 47:1440-7 |
