(572ab) Models of the Aging Cardiovascular System for the Study of Degenerative Diseases

Tools to aid in the design and testing of prosthetic hearts valves include cardiac pulse duplicators and computational fluid dynamics simulation. Typically, conditions in the pulse duplicators are well defined and controlled based on established guidelines for prosthetic valve testing. We have created a pulse duplicator to simulate the physiologic effects of the aging and diseased cardiovascular system, including increased aortic impedance (decreased compliance and increased resistance), and cardiac outputs representing heart failure as well as normal states. In this paper we will describe the design and validation of this cardiac pulse duplicator, and its use to study degenerative aortic valve disease. This is a progressive disease with an unpredictable rate of progression characterized by increased leaflet thickness, stiffening and calcification without commissural fusion. These changes increase resistance to cardiac outflow and hence the workload on the left ventricle. This will cause left ventricular hypertrophy and if untreated, heart failure and death. It is believed that ?wear and tear?, including mechanical stress injury to the endothelium on the valve, mediates the disease process. Risk factors for valve disease are similar for other cardiovascular disease (e.g., age, smoking, hypertension, and hyperlipidemia). Current hemodynamic measurements of the severity of aortic valve disease have little value in predicting progression or onset of symptoms. Early changes in the degenerative process include thickening and stiffening of the leaflets, reflected in altered rates of opening and closing, before becoming restrictive to flow. In this study, we tested the hypothesis that changes in ambient hemodynamic forces associated with aging and related cardiovascular disease (such as hypertension) affect valve mechanics and independently classic measurements of disease severity. For example, hypertension creates increased afterload for the left ventricle, due to increased peripheral resistance, decreased arterial distensibility, and early wave reflections because of increased wave propagation velocity. These contribute to a more rapid initial rise in aortic pressure, a higher systolic peak, and a more rapid fall in pressure during diastole compared to normal. These changes alter forces on the aortic valve and thus stress patterns within it. Data obtained in the pulse duplicator, combined with computational simulation, will be used to develop markers of the properties of the valve itself, independent of ambient hemodynamic state. Such measurements, if validated clinically, would be useful in predicting disease progression and in the design and assessment of new therapeutic strategy.