Experimental technique of measuring dynamic fluid shear stress on the aortic surface of the aortic valve leaflet

Aortic valve (AV) calcification is a highly prevalent disease with serious impact on mortality and morbidity. The exact cause and mechanism of the progression of AV calcification is unknown, although mechanical forces have been known to play a role. It is thus important to characterize the mechanical environment of the AV. In the current study, we establish a methodology of measuring shear stresses experienced by the aortic surface of the AV leaflets using an in vitro valve model and adapting the laser Doppler velocimetry (LDV) technique. The valve model was constructed from a fresh porcine aortic valve, which was trimmed and sutured onto a plastic stented ring, and inserted into an idealized three-lobed sinus acrylic chamber. Valve leaflet location was measured by obtaining the location of highest back-scattered LDV laser light intensity. The technique of performing LDV measurements near to biological surfaces as well as the leaflet locating technique was first validated in two phantom flow systems: (1) steady flow within a straight tube with AV leaflet adhered to the wall, and (2) steady flow within the actual valve model. Dynamic shear stresses were then obtained by applying the techniques on the valve model in a physiologic pulsatile flow loop. Results show that aortic surface shear stresses are low during early systole (<5 dyn/cm2) but elevated to its peak during mid to late systole at about 18-20 dyn/cm2. Low magnitude shear stress (<5 dyn/cm2) was observed during early diastole and dissipated to zero over the diastolic duration. Systolic shear stress was observed to elevate only with the formation of sinus vortex flow. The presented technique can also be used on other in vitro valve models such as congenitally geometrically malformed valves, or to investigate effects of hemodynamics on valve shear stress. Shear stress data can be used for further experiments investigating effects of fluid shear stress on valve biology, for conditioning tissue engineered AV, and to validate numerical simulations.     

Transcatheter aortic valve implantation

There has been significant improvement in device designs, operative techniques, and early clinical outcomes in <5 years. Presently, there are two catheter-based bioprostheses (balloon expandable or self-expandable), which have been widely used in humans and are undergoing clinical investigations. Three approaches, including transvenous, transarterial, and transapical have been used for delivery of the catheter-based bioprostheses, and transarterial and transapical approaches have been adopted by cardiologists and cardiac surgeons worldwide. The most recent clinical results have been very encouraging and promising. With experience, 30-day operative mortality with either balloon-expandable or self-expandable bioprosthesis was reduced significantly to approximately 10% in high-risk patients. In vivo long-term durability of catheter-based bioprostheses remains unknown, and presently transcatheter procedure is limited to the cohort of high-risk patients. Expanding this new technology to low-risk patients should be done with extreme caution because conventional aortic valve replacement still provides the best long-term outcome with minimal operative mortality and morbidity in low-risk patients. Ongoing clinical trials will address many unanswered questions, such as patient selection, long-term in vivo durability, preoperative assessment, and the role of the procedures in management of valvular diseases.     

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.     

Techniques of aortic valve repair

Similar to mitral repair, newer methods of aortic valve reconstruction are achieving excellent outcomes with an 85% to 90% freedom from valve-related complications at 10 years. The goal of this review is to illustrate these newer and more stable techniques of aortic valve repair. Most patients with aortic insufficiency from either trileaflet or bicuspid aortic valves are candidates for repair, in addition to selected patients with mixed aortic stenosis/insufficiency and aortic root aneurysms. Initially, aggressive commissural annuloplasty is performed to reduce measured valve diameter to 19 to 21 mm. Leaflet prolapse is corrected with plication stitches placed in the free edge of each leaflet adjacent to the Nodulus Arantius. In this regard, the leaflet free edge functions as the chorda tendinea of the aortic valve, and shortening with plication stitches raises the leaflet to a proper "effective height." Leaflet defects are augmented with gluteraldehyde-fixed autologous pericardium, and mild-to-moderate strategically placed spicules of calcium are removed with the cavitron ultrasonic surgical aspirator. Using these methods, most insufficient aortic valves, and many with mixed lesions, can be satisfactorily repaired. Six cases are illustrated in this review, spanning the spectrum of pathologies from annular dilatation without leaflet defects, to standard congenital bicuspid valve with prolapse, to trileaflet prolapse, to unusual bicuspid pathology with calcification, to a moderately calcified trileaflet valve with mixed lesions, and to aortic root aneurysms with severe aortic insufficiency. All valves were repaired using the techniques described above with trivial residual leak and minimal gradients. All repairs have been followed with yearly echocardiography, and valve reconstruction with these methods is now quite stable with excellent late outcomes. Most insufficient aortic valves now can undergo stable repair with minimal late valve-related complications. Greater application of aortic valve repair seems indicated.     

Syncope after aortic valve surgery

Netherlands Heart Journal -     

Myocardial adaptations in aortic valve disease.

Injections of human chorionic gonadotropin (HCG) have been claimed to aid in weight reduction by reducing hunger, and affecting mood as well as aiding in localized (spot) reduction. We have tested these claims in a double-blind randomized trial using injections of HCG or placebo. Weight loss was identical between the two groups, and there was no evidence for differential effects on hunger, mood or localized body measurements. Placebo injections, therefore, appear to be as effective as HCG in the treatment of obesity.     

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...     

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.     

Report on outcomes of valve-in-valve transcatheter aortic valve implantation and redo surgical aortic valve replacement in the Netherlands

Netherlands Heart Journal - We sought to investigate real-world outcomes of patients with degenerated biological aortic valve prostheses who had undergone valve-in-valve transcatheter aortic valve...     

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.     

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.     

Strain transfer through the aortic valve

The complex structural organization of the aortic valve (AV) extracellular matrix (ECM) enables large and highly nonlinear tissue level deformations. The collagen and elastin (elastic) fibers within the ECM form an interconnected fibrous network (FN) and are known to be the main load-bearing elements of the AV matrix. The role of the FN in enabling deformation has been investigated and documented. However, there is little data on the correlation between tissue level and FN-level strains. Investigating this correlation will help establish the mode of strain transfer (affine or nonaffine) through the AV tissue as a key feature in microstructural modeling and will also help characterize the local FN deformation across the AV sample in response to applied tissue level strains. In this study, the correlation between applied strains at tissue level, macrostrains across the tissue surface, and local FN strains were investigated. Results showed that the FN strain distribution across AV samples was inhomogeneous and nonuniform, as well as anisotropic. There was no direct transfer of the deformation applied at tissue level to the fibrous network. Loading modes induced in the FN are different than those applied at the tissue as a result of different local strains in the valve layers. This nonuniformity of local strains induced internal shearing within the FN of the AV, possibly exposing the aortic valve interstitial cells (AVICs) to shear strains and stresses.