Hyperlipidaemia and aortic valve disease

PURPOSE OF REVIEW: Degenerative aortic valve stenosis is a common disease in the elderly, and traditional risk factors for atherosclerotic disease including hyperlipidaemia have been associated with the condition in several studies. This review addresses the role of the various risk factors and the potential for intervention. RECENT FINDINGS: The association of lipid abnormalities such as high lipoprotein(a) levels and the presence of the apolipoprotein E4 allele with aortic stenosis, as well as the presence of several inflammatory markers both in plasma and in surgically excised valves, suggest that the stenotic process is driven by many of the same factors behind atherosclerosis. The aortic valves of animals fed a cholesterol-rich diet exhibit many characteristics in common with the early stages of aortic stenosis. This opens up the potential of retarding the process through intervention strategies. SUMMARY: Hyperlipidaemia is associated with degenerative aortic valve stenosis, and the disease resembles the inflammatory process of atherosclerosis. Randomized controlled clinical trials will be needed to demonstrate the role of lipid intervention in patients with this condition.     

Mechano-potential etiologies of aortic valve disease

Aortic valve leaflets experience varying applied loads during the cardiac cycle. These varying loads act on both cell types of the leaflets, endothelial and interstitial cells, and cause molecular signaling events that are required for repairing the leaflet tissue, which is continually damaged from the applied loads. However, with increasing age, this reparative mechanism appears to go awry as valve interstitial cells continue to remain in their ‘remodeling’ phenotype and subsequently cause the tissue to become stiff, which results in heart valve disease. The etiology of this disease remains elusive; however, multiple clues are beginning to coalesce and mechanical cues are turning out to be large predicators of cellular function in the aortic valve leaflets, when compared to the cells from the pulmonary valve leaflets, which are under a significantly less demanding mechanical loading regime. Finally, this paper discusses the mechanical environment of the constitutive cell populations, mechanobiological processes that are currently unclear, and a mechano-potential etiology of aortic disease will be presented.     

Impact of calcific aortic valve disease on valve mechanics

Biomechanics and Modeling in Mechanobiology - The aortic valve is a highly dynamic structure characterized by a transvalvular flow that is unsteady, pulsatile, and characterized by episodes of...     

Natural history and management of chronic aortic valve disease.

Chronic aortic valve disease involving stenosis, regurgitation or both is insidious and progressive. Severe valvular dysfunction may be present for years without symptoms, but functional deterioration is often rapid once congestive heart failure, angina or syncope with effort is present. As the severity of aortic stenosis may not be easy to assess clinically, the relative usefulness of various tests is considered in this paper. The difficulty with chronic aortic regurgitation lies not in diagnosing the problem but in detecting early left ventricular dysfunction in time to perform the surgery that can prevent further functional deterioration. Patients with significant aortic valve disease should undergo surgery when the important symptoms of dyspnea, angina or syncope with effort first appear. Surgery should also be considered in selected patients with aortic regurgitation in whom left ventricular function has diminished even without symptoms.     

Computational assessment of bicuspid aortic valve wall-shear stress: implications for calcific aortic valve disease

The bicuspid aortic valve (BAV) is associated with a high prevalence of calcific aortic valve disease (CAVD). Although abnormal hemodynamics has been proposed as a potential pathogenic contributor, the native BAV hemodynamic stresses remain largely unknown. Fluid-structure interaction models were designed to quantify the regional BAV leaflet wall-shear stress over the course of CAVD. Systolic flow and leaflet dynamics were computed in two-dimensional tricuspid aortic valve (TAV) and type-1 BAV geometries with different degree of asymmetry (10 and 16% eccentricity) using an arbitrary Lagrangian–Eulerian approach. Valvular performance and regional leaflet wallshear stress were quantified in terms of valve effective orifice area (EOA), oscillatory shear index (OSI) and temporal shear magnitude (TSM). The dependence of those characteristics on the degree of leaflet calcification was also investigated. The models predicted an average reduction of 49% in BAV peak-systolic EOA relative to the TAV. Regardless of the anatomy, the leaflet wall-shear stress was side-specific and characterized by high magnitude and pulsatility on the ventricularis and low magnitude and oscillations on the fibrosa. While the TAV and non-coronary BAV leaflets shared similar shear stress characteristics, the base of the fused BAV leaflet fibrosa exhibited strong abnormalities, which were modulated by the degree of calcification (6-fold, 10-fold and 16-fold TSM increase in the normal, mildly and severely calcified BAV, respectively, relative to the normal TAV). This study reveals the existence of major differences in wall-shear stress pulsatility and magnitude on TAV and BAV leaflets. Given the ability of abnormal fluid shear stress to trigger valvular inflammation, the results support the existence of a mechano-etiology of CAVD in the BAV.     

Myocardial biochemical and hemodynamic adaptations to chronic tachycardia.

The purpose was to determine the biochemical and hemodynamic adaptations of the myocardium to chronic tachycardia. Cardiac pacemakers were implanted in Yorkshire pigs and set at a rate of 180 beats/min for a period of 35-42 days. Animals were then anesthetized with pentobarbital sodium. Myocardial blood flow and hemodynamics were determined at three different heart rates (i.e., 120, 180, and 220 beats/min). Tissue samples were then taken for microsphere and biochemical analyses. Chronically paced hearts maintained better cardiac function and had consistently higher left ventricular blood flow with a higher endocardial-to-epicardial ratio. The activities of citrate synthase and 3-hydroxyacyl-CoA dehydrogenase were 23 and 45% greater in the paced hearts, respectively. The sarcoplasmic reticulum adenosinetriphosphatase activity was 55% greater in the paced hearts, whereas the myosin adenosinetriphosphatase was the same as in the control hearts. Polyacrylamide gels of the ventricular myosin isoforms showed only the V3 type to be present in both the control and paced hearts. These findings show that the heart of a large mammal adapts to chronic tachycardia (i.e., 180 beats/min) by elevating the aerobic and calcium-sequestering capacities without altering its myosin type.     

Calcification of matrix vesicles in human aortic valve and aortic media.

Calcification of human aortic valve and aortic media occurs regularly, increases with age, and is distinctively associated with a zone of lipid accumulation. Ultrastructurally, the accumulated lipids are seen as cellular degradation products derived from senescent and degenerate fibrocytes and smooth muscle cells. The products when deposited in the matrix are morphologically similar to the matrix vesicles described in other calcifying tissues, and serve as the initial site of calcification rather than collagen or elastic fibers. Scattered among the smaller and more typical matrix vesicles, there are seen frequently giant vesicle-like structures measuring several microns in diameter. Many of these large calcified bodies contain needle-shaped, radially arranged apatite crystal deposits. Some of the large calcifying bodies are bounded by folded structures suggesting a membrane component, at times obscured by a more dense floccular osmiophilic deposition. Alcianophilic apparent proteoglycan particles are also adherent to these large calcified bodies. The substance forming the large calcified bodies might be a complex of phospholipids derived from cell membrane and proteoglycan derived from ground substance, this combination possible serving as a nidus for calcification.     

Autophagy as mechanism for cell death in degenerative aortic valve disease

Once degenerative aortic valve disease becomes symptomatic, valve replacement is necessary for prognostic and symptomatic reasons. In elderly patients, symptoms of degenerative aortic valve can often be doubtful. Therefore, it is difficult but important to distinguish patients who need surgery from those who do not. Estimation of the rate of the progression of this disease can be helpful herein because one needs to bear in mind that aortic valve degeneration is an active process, which can influence the rate of progression. Recently, autophagy was discovered as a mechanism of cell death in different cardiovascular diseases such as atherosclerosis, aortic valve degeneration, heart failure and at regions around heart infarctions. Thus understanding autophagy in all its details can be helpful to contribute insights into the cell death machinery of cardiovascular diseases. This could open ways for inhibition of cell death in cardiovascular disease and possibly define targets for future drug design.