新型机械心脏瓣膜的研究

目前临床使用的各种机械心脏瓣膜的主要问题是血栓栓塞和与抗凝治疗有关的出血,其缺陷在于瓣膜开启时,碟片和支架将瓣膜的整个血流通道分隔成三至四个较小的血流通道。在这种受阻隔的血流通宫,形成容易诱发血栓的高剪应力区、紊流和滞流区。我们研制的两种机械心脏瓣膜在瓣膜开启时,没有任何支架和碟片分隔瓣膜的血流通道,使血流与天然心脏瓣膜中的相类似,可减少对血液的危害,从而可减少换瓣病人对抗凝治疗的依赖程度。     

Platelet activation of mechanical versus bioprosthetic heart valves during systole

Thrombus formation is a major concern for recipients of mechanical heart valves (MHVs), which requires them to take anticoagulant drugs for the rest of their lives. Bioprosthetic heart valves (BHVs) do not require life-long anticoagulant therapy but deteriorate after 10–15 years. The thrombus formation is initiated by the platelet activation which is thought to be mainly generated in MHVs by the flow through the hinge and the leakage flow during the diastole. However, our results show that the activation in the bulk flow during the systole phase might play an essential role as well. This is based on our results obtained by comparing the thrombogenic performance of a MHV and a BHV (as control) in terms of shear induced platelet activation under exactly the same conditions. Three different mathematical activation models including linear level of activation, damage accumulation, and Soares model are tested to quantify the platelet activation during systole using the previous simulations of the flow through MHV and BHV in a straight aorta under the same physiologic flow conditions. Results indicate that the platelet activation in the MHV at the beginning of the systole phase is slightly less than the BHV. However, at the end of the systole phase the platelet activation by the bulk flow for the MHV is several folds (1.41, 5.12, and 2.81 for linear level of activation, damage accumulation, and Soares model, respectively) higher than the BHV for all tested platelet activation models.     

Modeling technique of prosthetic heart valves

This paper demonstrates a modeling technique of prosthetic heart valves. In the modeling, a pumping cycle is divided into four phases, in which the state of the valve and flow is different. The pressure-flow relation across the valve is formulated separately in each phase. This technique is developed to build a mathematical model used in the real time estimation of the hemodynamic state under artificial heart pumping. The model built by this technique is simple enough for saving the computational time in the real time estimation. The model is described by the first-order ordinary differential equation with 12 parameters. These parameters can be uniquely determined beforehand from in-vitro experimental data. It is shown that the model can adapt, with sufficient accuracy, to a change in the practical pumping condition and the viscosity of the fluid in their practical range, and is also demonstrated that the estimated backflow volume by model agrees closely with the actual one.     

Prosthetic valves in adult patients with congenital heart disease: Rationale and design of the Dutch PROSTAVA study

Background

Data on long-term complications in adult patients with congenital heart disease (ACHD) and a prosthetic valve are scarce. Moreover, the influence of prosthetic valves on quality of life (QoL) and functional outcome in ACHD patients with prosthetic valves has not been studied.

Objectives

The primary objective of the PROSTAVA study is to investigate the relation between prosthetic valve characteristics (type, size and location) and functional outcome as well as QoL in ACHD patients. The secondary objectives are to investigate the prevalence and predictors of prosthesis-related complications including prosthesis-patient mismatch.

Methods

The PROSTAVA study, a multicentre cross-sectional observational study, will include approximately 550 ACHD patients with prosthetic valves. Primary outcome measures are maximum oxygen uptake during cardiopulmonary exercise testing and QoL. Secondary outcomes are the prevalence and incidence of valve-related complications including prosthesis-patient mismatch. Other evaluations are medical history, physical examination, echocardiography, MRI, rhythm monitoring and laboratory evaluation (including NT-proBNP).

Implications

Identification of the relation between prosthetic valve characteristics in ACHD patients on one hand and functional outcome, QoL, the prevalence and predictors of prosthesis-related complications on the other hand may influence the choice of valve prosthesis, the indication for more extensive surgery and the indication for re-operation.     

High resolution three-dimensional strain mapping of bioprosthetic heart valves using digital image correlation

Transcatheter aortic valve replacement (TAVR) is a safe and effective treatment option for patients deemed at high and intermediate risk for surgical aortic valve replacement. Similar to surgical aortic valves (SAVs), transcatheter aortic valves (TAVs) undergo calcification and mechanical wear over time. However, to date, there have been limited publications on the long-term durability of TAV devices. To assess longevity and mechanical strength of TAVs in comparison to surgical bioprosthetic valves, three-dimensional deformation analysis and strain measurement of the leaflets become an inevitable part of the evaluation. The goal of this study was to measure and compare leaflet displacement and strain of two commonly used TAVs in a side-by-side comparison with a commonly used SAV using a high-resolution digital image correlation (DIC) system. 26-mm Edwards SAPIEN 3, 26-mm Medtronic CoreValve, and 25-mm Carpentier-Edwards PERIMOUNT Magna surgical bioprosthesis were examined in a custom-made valve testing apparatus. A time-varying, spatially uniform pressure was applied to the leaflets at different loading rates. GOM ARAMIS® software was used to map leaflet displacement and strain fields during loading and unloading. High displacement regions were found to be at the leaflet belly region of the three bioprosthetic valves. In addition, the frame of the surgical bioprosthesis was found to be remarkably flexible, in contrary to CoreValve and SAPIEN 3 in which the stent was nearly rigid under a similar loading condition. The experimental DIC measurements can be used to characterize the anisotropic materiel behavior of the bioprosthetic heart valve leaflets and validate heart valve computational simulations.     

Structural simulations of prosthetic tri-leaflet aortic heart valves

This study presents a combined computational and experimental approach for the nonlinear structural simulations of polymeric tri-leaflet aortic valves (PAVs). Nonlinear shell-based and quasi-static finite-element (FE) structural models are generated for a prosthetic valve geometry that includes the leaflets, stents and root materials, such as the bottom base and outside walls. The PAV structural model is subject to an ensemble averaged transvalvular pressure waveform measured from repeated in vitro tests conducted with a left heart simulator. High-resolution optical measurements are used to measure the in vitro kinematics of the leaflets and the stents. Qualitative and quantitative deformation measures are defined in order to compare the predicted kinematics from the PAV models with the in vitro measurements. Six new quantitative deformation metrics are introduced. They include three distances measuring the current PAV geometric center to the leaflet edges while additional three distances define the stent post-to-stent post (SPTSP) distances. The structural model is able to predict the kinematic deformation metrics with maximum errors around 10% especially in systole where the displacements are larger in magnitude. The combined structural modeling with experimental simulations along with the new proposed deformation metrics provide an effective way to study the PAV structural behavior and a path for improving the structural design of prosthetic valves.     

Laser assessment of leaflet closing motion in prosthetic heart valves

The dynamics of leaflet motion in heart valve prostheses (HVP), and in particular the closing velocity, is believed to be related to the valve sound and possibly to the phenomenon of valve cavitation. This paper describes a non-intrusive laser sweeping technique enabling the study of leaflet motion. The principle of measurement and the equipment involved are presented, together with the results of two commerially available, 29 mm bileaflet mitral valves, a St. Jude Medical, and an Edwards Duromedic valve. Experiments were carried out in a pulsatile mock flow testing loop designed to mimic physiological pressure waveforms and ventricular contraction. Measurements of heart rate were made in the range 70–120 beats min⁻¹, with a ventricular pressure slope range of 1800–5600 mm Hgs⁻¹ and a cardiac output range of 5.0–7.5 litres min⁻¹. Motion analysis of the measured data focuses on the velocity of the leaflet immediately before closure.     

Anti-calcification of bovine pericardium for bioprosthetic heart valves after surface modification with hyaluronic acid derivatives

Surface modification of glutaraldehyde fixed bovine pericardium (GFBP) was successfully carried out with hyaluronic acid (HA) derivatives. At first, HA was chemically modified with adipic dihydrazide (ADH) to introduce hydrazide functional group into the carboxyl group of HA backbone. Then, GFBP was surface modified by grafting HA-ADH to the free aldehyde groups on the tissue and the subsequent HA-ADH hydrogel coating. HA-ADH hydrogels could be prepared through selective crosslinking at low pH between hydrazide groups of HA-ADH and crosslinkers containing succinimmidyl moieties with minimized protein denaturation. When HA-ADH hydrogels were prepared at low pH of 4.8 in the presence of erythropoietin (EPO) as a model protein, EPO release was continued up to 85% of total amount of loaded EPO for 4 days. To the contrary, only 30% of EPO was released from HA-ADH hydrogels prepared at pH=7.4, which might be due to the denaturation of EPO during the crosslinking reaction. Because the carboxyl groups on the glucuronic acid residues are recognition sites for HA degradation by hyaluronidase, the HA-ADH hydrogels degraded more slowly than HA hydrogels prepared by the crosslinking reaction of divinyl sulfone with hydroxyl groups of HA. Following a two-week subcutaneous implantation in osteopontin-null mice, clinically significant levels of calcification were observed for the positive controls without any surface modification. However, the calcification of surface modified GFBP with HA-ADH and HA-ADH hydrogels was drastically reduced by more than 85% of the positive controls. The anti-calcification effect of HA surface modification was also confirmed by microscopic analysis of explan ted tissue after staining with Alizarin Red S for calcium, which followed the trend as observed with calcium quantification.     

Periostin expression by epicardium-derived cells is involved in the development of the atrioventricular valves and fibrous heart skeleton

Abstract The epicardium is embryologically formed by outgrowth of proepicardial cells over the naked heart tube. Epicardium-derived cells (EPDCs) migrate into the myocardium, contributing to myocardial architecture, valve development, and the coronary vasculature. Defective EPDC formation causes valve malformations, myocardial thinning, and coronary defects. In the atrioventricular (AV) valves and the fibrous heart skeleton isolating atrial from ventricular myocardium, EPDCs colocalize with periostin, a matrix molecule involved in remodeling. We investigated whether proepicardial outgrowth inhibition affected periostin expression and how this related to development of the AV valves and fibrous heart skeleton.
Periostin expression by epicardium and EPDCs was confirmed in vitro in primary cultures of human and quail EPDCs. Disturbing EPDC formation in quail embryos reduced periostin expression in the endocardial cushions and AV junction. Disturbed fibrous tissue development resulted in AV myocardial connections reflected by preexcitation electrocardiographic patterns.
We conclude that EPDCs are local producers of periostin. Disturbance of EPDC formation results in decreased cardiac periostin levels and hampers the development of fibrous tissue in AV junction and the developing AV valves. The resulting cardiac anomalies might link to Wolff–Parkinson White syndrome with persistent AV myocardial connections.