Heart Valve Function Research Articles

Structural Integrity of Balloon-Expandable Stents After Transcatheter Aortic Valve Replacement: Assessment by Multidetector Computed Tomography

This study sought to evaluate the structural integrity of balloon-expandable stents used in transcatheter aortic valve replacement. Underexpansion, deformation, or fracture of stent frames may affect transcatheter heart valve (THV) function and durability. Patients >1 year after transcatheter aortic valve replacement underwent multidetector computed tomography. Geometry of the stent frame was assessed for circularity; eccentricity; minimum and maximum external diameter; and expansion at the inflow, mid-stent, and outflow levels, as well as for stent fracture. THV noncircularity was defined as stent eccentricity >10% (1 - minimum diameter/maximum diameter) and THV underexpansion when expansion <90% (multidetector computed tomography derived external valve area/nominal external valve area). Echocardiography was performed after implantation and annually. Fifty patients underwent multidetector computed tomography at an average of 2.5 ± 0.9 years after transcatheter aortic valve replacement (35 Sapien, 8 Sapien XT, and 7 Cribier-Edwards valves [all Edwards Lifesciences, Irvine, California). The mean external diameter for the 23- and 26-mm valves was 23.3 ± 0.9 mm and 25.9 ± 0.9 mm, respectively. Circularity was present in 96% (48 of 50) and median eccentricity was 2.0% (interquartile range: 1.2% to 3.0%). Mean THV expansion was 104.1 ± 7.4%, which increased from stent inflow to outflow (100.8 ± 7.6% vs. 108.1 ± 6.9%, p < 0.001). Stent fracture was not observed. Underexpanded valves (8% [4 of 50]) and noncircular valves (4% [2 of 50]) demonstrated stable hemodynamic function on annual echocardiography. Balloon-expandable aortic valves have excellent rates of circularity with low eccentricity and maintain full expansion without stent fracture at an average 2.5 years after implantation.

Tissue‐Engineered Heart Valve: Future of Cardiac Surgery

Heart valve disease is currently a growing problem, and demand for heart valve replacement is predicted to increase significantly in the future. Existing "gold standard" mechanical and biological prosthesis offers survival at a cost of significantly increased risks of complications. Mechanical valves may cause hemorrhage and thromboembolism, whereas biologic valves are prone to fibrosis, calcification, degeneration, and immunogenic complications. A literature search was performed to identify all relevant studies relating to tissue-engineered heart valve in life sciences using the PubMed and ISI Web of Knowledge databases. Tissue engineering is a new, emerging alternative, which is reviewed in this paper. To produce a fully functional heart valve using tissue engineering, an appropriate scaffold needs to be seeded using carefully selected cells and proliferated under conditions that resemble the environment of a natural human heart valve. Bioscaffold, synthetic materials, and preseeded composites are three common approaches of scaffold formation. All available evidence suggests that synthetic scaffolds are the most suitable material for valve scaffold formation. Different cell sources of stem cells were used with variable results. Mesenchymal stem cells, fibroblasts, myofibroblasts, and umbilical blood stem cells are used in vitro tissue engineering of heart valve. Alternatively scaffold may be implanted and then autoseeded in vivo by circulating endothelial progenitor cells or primitive circulating cells from patient's blood. For that purpose, synthetic heart valves were developed. Tissue engineering is currently the only technology in the field with the potential for the creation of tissues analogous to a native human heart valve, with longer sustainability, and fever side effects. Although there is still a long way to go, tissue-engineered heart valves have the capability to revolutionize cardiac surgery of the future.

The Importance of Transesophageal Echocardiography in Heart Harvesting for Cardiac Transplantation

The use of transesophageal echocardiography (TEE) during heart harvesting for transplantation can guide the heart assessment, as harvesting a marginal heart can jeopardize the cardiac transplantation. Male, 30 years old, suffered a car crash that resulted in a severe traumatic brain injury (TBI) that evolved to brain death. The patient was intubated and ventilated with a fraction of inspired oxygen of 0.6, presetting Vt 500 mL, RR 14 bpm, PEEP of 3 mm Hg, 99% O(2) saturation, and normal blood gases. He was also hypovolemic, with urine output of 9,300 mL.day(-1), sodium level of 157 mEq.L(-1), hematocrit of 27%, and BP 90/60 mm Hg maintained by infusion of norepinephrine 0.5 mcg.kg.min(-1). The patient was clinically optimized and evaluated by TEE, which showed normal size cardiac chambers, ejection fraction 66%, anatomical and functional heart valves with no changes, and foramen ovale integrity. Immediately after the confirmation of cardiac viability and clinical stabilization, the patient was taken to the operating room and the harvest began. The ischemic period lasted two hours and the heart was successfully transplanted. In most heart transplant services, the cardiac assessment is made subjectively by the surgeon who often does not have the anesthesiologist support to clinically optimize the donor. At the Instituto Nacional de Cardiologia (INC/MS), the anesthesiologist is part of the harvesting team in order to perform intraoperative TEE, evaluating objectively the harvested heart. In doing so, it provides greater chances of heart transplantation success with lower costs for the Brazilian public health system.

Enhanced Autologous Re-endothelialization of Decellularized and Extracellular Matrix Conditioned Allografts Implanted Into the Right Ventricular Outflow Tracts of Juvenile Sheep

Decellularized allografts are promising options for pediatric valve replacement due to reduced immunogenicity and the potential for in vivo autologous recellularization, extracellular matrix (ECM) remodeling and re-endothelialization, which may be enhanced with post-decellularization processing steps. This study investigated the performance and morphology of decellularized and ECM conditioned pulmonary valves implanted in the right ventricular outflow tracts (RVOT) of juvenile sheep. RVOT reconstructions in juvenile sheep using cryopreserved pulmonary allografts (Cryo; n = 2), porcine aortic root bioprostheses (Biopros; n = 2) or decellularized/ECM conditioned pulmonary allografts (Conditioned; n = 4) were performed. Valve performance and morphology were evaluated at 20 weeks after implant. Uniaxial tensile testing was performed on a subset of unimplanted valves from each group. At explant, Biopros had significantly higher peak/mean gradients vs. Conditioned and Cryo, which were similar. No cusp calcification occurred in any valve; arterial wall calcification was present only in Cryo (mild/moderate) and Biopros (severe). No autologous recellularization or inflammation occurred in Biopros; cellularity was decreased in Cryo. Autologous recellularization was present in Conditioned arterial walls and variably extending into the cusps, with consistent cusp re-endothelialization. Conditioned valves had reduced cusp extensibility, increased stiffness and similar tensile strength vs. Cryo. Although Conditioned valves were slightly stiffer and less extensible than Cryo valves, their hemodynamic performance was comparable, indicating they behave as functional heart valves immediately following implant. Because both autologous recellularization and re-endothelialization were seen, ECM conditioning shows promise for encouraging renewal of the cellularity of decellularized allograft valves without the need for pre-implant endothelial cell seeding.

Impact of γ-Irradiation on Extracellular Matrix of Porcine Pulmonary Valves

The extracellular matrix plays an important role in heart valve function. To improve the processing of porcine pulmonary valves for clinical use, we have studied the influence of cryopreservation, decellularization, and irradiation on extracellular matrix components. Decellularization was carried out followed by DNAseI/RNAseA digestion and isotonic washout. Valves were cryopreserved in 10% DMSO/10% fetal bovine serum, and then subjected to 25-40 kGy γ-radiation. Extracellular matrix constituents were evaluated by histologic staining, immunohistochemistry, transmission electron microscopy, and liquid chromatography/mass spectrometry. Histologic, immunohistochemical, ultrastructural, and biochemical analyses demonstrated a marked reduction in the expression of extracellular matrix components particularly in the valves that had been γ-irradiated following decellularization and cryopreservation. In this group, histology and immunohistochemistry showed an obvious reduction in staining for chondroitin sulphates, versican, hyaluronan, and collagens. Transmission electron microscopy revealed the smallest fibril diameter of collagen, shortest D-period, and loss of compactness of collagen fiber packaging and fragmentation of elastic fibers. Biochemical analysis showed loss of collagen and elastin crosslinks. Decellularization followed by cryopreservation showed some reduction in staining for collagens and versican, smaller diameter, shorter D-period in collagen fibers, and ridges in elastic fibers. Cryopreservation alone showed minimal changes in ECM staining intensity, collagen, and elastin ultrastructure and biochemistry. γ-Irradiated valves that have been decellularized and cryopreserved produces significant changes in the expression of ECM components, thus providing useful information for improving valve preparation for clinical use and also some indication as to why irradiated human heart valves were not clinically successful.

Mechanisms of Function and Disease of Natural and Replacement Heart Valves

Over the past several decades, there has been substantial progress toward understanding the mechanisms of heart valve function and dysfunction. This review summarizes an evolving conceptual framework of heart valve functional structure, developmental biology, and pathobiology and explores the implications of key insights. I emphasize: (a) valve cell and extracellular matrix biology and the impact of biomechanical factors on function, homeostasis, environmental adaptation, and key pathological processes; (b) the role of developmental processes, valvular cell behavior, and extracellular matrix remodeling in congenital and acquired valve abnormalities; and (c) the cell/matrix biology of degeneration in replacement tissue valves. I also summarize how these considerations may ultimately inform the potential for prevention and treatment of major diseases and potentially therapeutic regeneration of the cardiac valves. Recent advances and opportunities for research and clinical translation are highlighted.

A One-Year Randomized Trial of Lorcaserin for Weight Loss in Obese and Overweight Adults: The BLOSSOM Trial

Lorcaserin is a novel selective agonist of the serotonin 2C receptor. Our objective was to evaluate the effects of lorcaserin on body weight, cardiovascular risk factors, and safety in obese and overweight patients. This randomized, placebo-controlled, double-blind, parallel arm trial took place at 97 U.S. research centers. Patients included 4008 patients, aged 18-65 yr, with a body mass index between 30 and 45 kg/m(2) or between 27 and 29.9 kg/m(2) with an obesity-related comorbid condition. Patients were randomly assigned in a 2:1:2 ratio to receive lorcaserin 10 mg twice daily (BID), lorcaserin 10 mg once daily (QD), or placebo. All patients received diet and exercise counseling. The ordered primary endpoints were proportion of patients achieving at least 5% reduction in body weight, mean change in body weight, and proportion of patients achieving at least 10% reduction in body weight at 1 yr. Serial echocardiograms monitored heart valve function. Significantly more patients treated with lorcaserin 10 mg BID and QD lost at least 5% of baseline body weight (47.2 and 40.2%, respectively) as compared with placebo (25.0%, P < 0.001 vs. lorcaserin BID). Least squares mean (95% confidence interval) weight loss with lorcaserin BID and QD was 5.8% (5.5-6.2%) and 4.7% (4.3-5.2%), respectively, compared with 2.8% (2.5-3.2%) with placebo (P < 0.001 vs. lorcaserin BID; least squares mean difference, 3.0%). Weight loss of at least 10% was achieved by 22.6 and 17.4% of patients receiving lorcaserin 10 mg BID and QD, respectively, and 9.7% of patients in the placebo group (P < 0.001 vs. lorcaserin BID). Headache, nausea, and dizziness were the most common lorcaserin-related adverse events. U.S. Food and Drug Administration-defined echocardiographic valvulopathy occurred in 2.0% of patients on placebo and 2.0% on lorcaserin 10 mg BID. Lorcaserin administered in conjunction with a lifestyle modification program was associated with dose-dependent weight loss that was significantly greater than with placebo.

Heart Valve Structure and Function in Development and Disease

The mature heart valves are made up of highly organized extracellular matrix (ECM) and valve interstitial cells (VICs) surrounded by an endothelial cell layer. The ECM of the valves is stratified into elastin-, proteoglycan-, and collagen-rich layers that confer distinct biomechanical properties to the leaflets and supporting structures. Signaling pathways have critical functions in primary valvulogenesis as well as the maintenance of valve structure and function over time. Animal models provide powerful tools to study valve development and disease processes. Valve disease is a significant public health problem, and increasing evidence implicates aberrant developmental mechanisms underlying pathogenesis. Further studies are necessary to determine regulatory pathway interactions underlying valve pathogenesis in order to generate new avenues for novel therapeutics.

Cells, scaffolds and bioreactors for tissue-engineered heart valves: a journey from basic concepts to contemporary developmental innovations☆

The development of viable and functional tissue-engineered heart valves (TEHVs) is a challenge that, for almost two decades, the scientific community has been committed to face to create life-lasting prosthetic devices for treating heart valve diseases. One of the main drawbacks of tissue-based commercial substitutes, xenografts and homografts, is their lack of viability, and hence failure to grow, repair, and remodel. In adults, the average bioprostheses life span is around 13 years, followed by structural valve degeneration, such as calcification; in pediatric, mechanical valves are commonly used instead of biological substitutes, as in young patients, the mobilization of calcium, due to bone remodeling, accelerates the calcification process. Moreover, neither mechanical nor bioprostheses are able to follow children's body growth. Cell seeding and repopulation of acellular heart valve scaffolds, biological and polymeric, appears as a promising way to create a living valve. Biomechanical stimuli have significant impact on cell behavior including in vitro differentiation, and physiological hemodynamic conditioning has been found to promote new tissue development. These concepts have led scientists to design bioreactors to mimic the in vivo environment of heart valves. Many different types of somatic and stem cells have been tested for colonizing both the surface and the core of the valve matrix but controversial results have been achieved so far.

Isolation and Culture of Avian Embryonic Valvular Progenitor Cells

Proper formation and function of embryonic heart valves is critical for developmental progression. The early embryonic heart is a U-shaped tube of endocardium surrounded by myocardium. The myocardium secretes cardiac jelly, a hyaluronan-rich gelatinous matrix, into the atrioventricular (AV) junction and outflow tract (OFT) lumen. At stage HH14 valvulogenesis begins when a subset of endocardial cells receive signals from the myocardium, undergo endocardial to mesenchymal transformation (EMT), and invade the cardiac jelly. At stage HH25 the valvular cushions are fully mesenchymalized, and it is this mesenchyme that eventually forms the valvular and septal apparatus of the heart. Understanding the mechanisms that initiate and modulate the process of EMT and cell differentiation are important because of their connection to serious congenital heart defects. In this study we present methods to isolate pre-EMT endocardial and post-EMT mesenchymal cells, which are the two different cell phenotypes of the prevalvular cushion. Pre-EMT endocardial cells can be cultured with or without the myocardium. Post-EMT AV cushion mesenchymal cells can be cultured inside mechanically constrained or stress-free collagen gels. These 3D in vitro models mimic key valvular morphogenic events and are useful for deconstructing the mechanisms of early and late stage valvulogenesis.

Drug-induced Valvulopathy: An Update

Drug-induced valvulopathy is a serious liability for certain compound classes in development and for some marketed drugs intended for human use. Reports of valvulopathy led to the withdrawal of fenfluramines (anorexigens) and pergolide (antiparkinson drug) from the United States market in 1997 and 2007, respectively. The mechanism responsible for the pathogenesis of valvulopathy by these drugs is likely a result of an "off-target" effect via activation of 5-hydroxytryptamine (5-HT) 2B receptor (5-HT2BR) expressed on heart valve leaflets. Microscopically, the affected valve leaflets showed plaques of proliferative myofibroblasts in an abundant extracellular matrix, composed primarily of glycosaminoglycans. However, the valvular effects caused by fenfluramines and pergolide were not initially predicted from routine preclinical toxicity studies, and to date there are no specific validated animal models or preclinical/toxicologic screens to accurately predict drug-induced valvulopathy. This review covers the structure and function of heart valves and highlights major advances toward understanding the 5-HT2BR-mediated pathogenesis of the lesion and subsequently, development of appropriate animal models using novel techniques/experiments, use of functional screens against 5-HT2BR, and more consistent sampling and pathologic evaluation of valves in preclinical studies that will aid in avoidance of future drug-induced valvulopathy in humans.

Tissue-Engineered Heart Valves Develop Native-like Collagen Fiber Architecture

Creating autologous tissues with on-demand and native-like biomechanical properties is the ultimate challenge in functional heart valve tissue engineering. A promising approach toward this goal is to induce development of native-like tissue structure in vitro by mimicking the diastolic loading phase in a bioreactor. Heart valves cultured with this approach showed in vitro sufficient strength to withstand systemic pressures. This study aims to link global functioning of these valves to the development of a native-like fiber architecture induced by in vitro diastolic loading. It is hypothesized that increased loading magnitude during culture will lead to increased collagen fiber alignment. To test this hypothesis, 10 tissue-engineered heart valves were subjected to different loading protocols in vitro. Local fiber distribution and mechanics were determined in an inverse numerical-experimental approach, combining indentation tests with confocal imaging. Indentation tests on native ovine heart valves were used as a comparison. Although the effect of loading magnitude was small within the tested range, results indicated that the local fiber architecture indeed developed toward native structural properties for all loading protocols. However, apparent fiber mechanics were much stiffer compared with native. This confirms that in vitro mechanical conditioning induces development of a native-like tissue architecture, which underlines its importance for functional heart valve tissue engineering.

Retrograde left‐ventricular hemodynamic assessment of mechanical aortic and mitral valve gradients using a high‐fidelity pressure wire: A case series

Noninvasive assessment of mechanical heart valve function with echocardiography is challenging. There are important safety issues when considering placing a standard catheter across a mechanical valve with for invasive hemodynamic measurements. The feasibility of using a high-fidelity micromanometer coronary pressure guide wire to assess hemodynamics across mechanical valves has been reported. Although this method appears feasible, safe, and free of major complication, its application and utility remains obscure and underappreciated. We report a series of two patients with mitral and aortic (St. Jude and Björk-Shiley) mechanical valves in which we successfully used this pressure wire technique to assess valvular function in patients evaluated for repeat surgical valve replacement. We include the first report of this guide wire technique to assess hemodynamics across a Björk-Shiley single-tilting disk valve.

Beat-rate Dependent Mitral Flow Patterns forin VitroHemodynamic Applications

The conservative surgery approach for restoring the functionality of heart valves has predominated during the last two decades, particularly for the mitral valve. In vitro pulsatile testing is a key methodology for the investigation of heart valve hemodynamics, and particularly for the ideation, validation and optimization of novel techniques in heart valve surgery. Traditionally, however, pulsatile mock loops have been developed for the study of aortic valve substitutes, and scarce attention has been paid in replicating the mitral flow patterns with due hemodynamic fidelity. In this work we provide detailed analytical expressions to produce beat-rate dependent, physiologic-like mitral flow patterns for in vitro applications. The approach we propose is based on a biomechanical analysis of the factors which govern hemodynamic changes in the mitral flow pattern, namely in terms of E and A wave contours and E/A peaks ratio, when switching from rest to mild exercise conditions. The patterns from the model we obtained were in good agreement with clinical literature data in terms of i) gradual superimposition of the E and A wave, which yielded a single peak at 96 bpm; ii) decrease in the E/A ratio with increasing heart rate; iii) amount of flow delivered by each of the two waves. The proposed method provides a physiologically representative, beat-rate dependent analytical expression of the mitral flow pattern, which can be used in in vitro hydrodynamic investigations to accurately replicate the changes that the flow waves experience when the heart rate shifts from rest to mild exercise conditions.

Evaluation of Mechanical Heart Valve Size and Function With ECG-Gated 64-MDCT

The purpose of our study was to determine whether CT can accurately evaluate mechanical heart valve size and function. Sixty-two patients with mechanical valves (37 single-disc, 27 bileaflet; 59 aortic, 5 mitral) were evaluated with ECG-gated 64-MDCT and transthoracic echocardiography; a subset of 10 patients underwent cinefluoroscopy. Two readers independently interpreted each study. The mean age of the patients was 46.4 +/- 14.4 years; 50 were men and 12 were women. There was excellent correlation, and differences between CT readers were absent to small in measuring the opening angle (r = 0.96, p < 0.001; 76.7 +/- 9.0 degrees vs 76.8 +/- 9.6 degrees , p = 0.73), annulus diameter (r = 0.96, p < 0.001; 25.9 +/- 3.3 vs 25.9 +/- 3.2 mm, p = 0.62), and geometric orifice area (r = 0.98, p < 0.001; 3.8 +/- 0.9 vs 3.6 +/- 0.8 cm(2), p < 0.001). There was strong correlation without difference in opening angle between CT and cinefluoroscopy (r = 0.77, p < 0.001; 79.2 degrees +/- 9.8 degrees vs 77.2 degrees +/- 15.5 degrees , p = 0.45). Compared with manufacturer specifications, CT reported opening angles that were smaller for single-disc valves (n = 36, 67.4 degrees +/- 5.7 degrees vs 75 degrees , p < 0.001) and similar for bileaflet valves (n = 42 for 21 valves, 83.8 degrees +/- 3.9 degrees vs 85 degrees , p = 0.05), valves, with small underestimation with CT versus specifications in annulus diameter (n = 41; r = 0.75, p < 0.001; 26.4 +/- 3.0 vs 27.5 +/- 3.3 mm, p = 0.003), and geometric orifice area (n = 35; r = 0.90, p < 0.001; 3.7 +/- 0.7 vs 3.8 +/- 0.8 cm(2), p = 0.04). Each disc closed fully on CT; none had more than mild regurgitation on echocardiography. CT can measure the size and function of mechanical valves with high interobserver agreement and results similar to specifications. The opening angle with CT strongly correlates with cinefluoroscopy. CT is promising for the assessment of mechanical valves.

Analysis of a mechanical heart valve prosthesis and a native venous valve: Two distinct applications of FSI to biomedical applications

AbstractThis paper reports the application of two commercial codes to the study of distinct cardiovascular problems: dynamics of a mechanical heart valve prosthesis and function of a native venous valve. The choice of code is driven by the characteristics of the problem. The ANSYS‐CFX implicit finite volume code is employed for the mechanical valve where the solution is dominated by the interaction between the local fluid domain and the rigid valve leaflets. The LS‐DYNA explicit dynamics code is used due to the stability of this approach when applied to systems with very flexible structural components such as the leaflets of a venous valve. The mechanical valve dynamics remain consistent for a range of mesh densities and residual criteria but begin to vary once the solution time step is increased above 2E–4 s. Venous valve function after application of a gravitational body load is shown to be dependent on parent vessel elastic modulus, E. The venous valve initially closes to a greater extent with a ‘softer’ parent vessel. Both approaches show promise for further study of these biomedical systems including the cavitation and thrombotic potential of mechanical valves and the local residence of blood constituents in the region of venous valve sinuses. Copyright © 2009 John Wiley &amp; Sons, Ltd.

Rechtsseitige Kunstklappenthrombose

A 33-year-old woman (Pt. A) with a prosthetic cardiac valve in the pulmonary position [CarboMedics bileaflet valve, diameter 23 mm] as part of the repair of a tetralogy of Fallot 4 years previously, and a 51-year-old woman (Pt. B) with a prosthetic cardiac valve [St. Jude Medical bileaflet valve, diameter 31 mm] inserted in tricuspid position as replacement of a degenerated Hancock bioprosthetic valve inserted 15 years previously, 10 years after an episode of endocarditis, were admitted to hospital with dyspnea and chest pain and dyspnea and tachycardia, respectively. Pt. A had a 3 - 4/6 crescendo-decrescendo systolic murmur and a 2/6 early diastolic decrescendo murmur over the 2nd to 4th right intercostal space (ICS), while Pt. B had a 3/6 holosystolic murmur and a 2 - 3/6 diastolic murmur over the 4th right ICS. Closing click was missing in both patients. Blood tests demonstrated an elevated LDH (404 U/l) in Pt. A and an elevated GGT (108 U/l) and fibrinogen (449 mg/dl) in Pt. B. Anticoagulation was below the therapeutic level, with an INR value of 1,65 and 1,93, respectively. The electrocardiogram showed sinus rhythm, right bundle branch block and an isoelectric ST-segment (Pt. A) and a typical high-frequency atrial flutter with a 2:1 block, right bundle branch block and terminal T-wave inversions in leads V1 to V5 (Pt. B). Cinefluoroscopy showed rigid and hypomobile leaflets as a result of prosthetic cardiac valve thrombosis. Doppler echocardiography confirmed the stenosis of the prosthetic valve in the pulmonary position (peak gradient 73 mm Hg, mean gradient 34 mm Hg) and the tricuspid position (mean gradient 8.48 mm Hg, peak gradient 16.73 mm Hg). Both patients were treated with unfractionated heparin and urokinase single-bolus injection of 4400 U/kg over 10 min followed by an infusion of 4400 U/kg/h over 12 h. Both patients had an abnormal opening angle, which improved to a normal opening and closing angle. Doppler echocardiography demonstrated decreased peak (18.0 and 6.6 mm Hg, respectively) and median gradients (9.0 and 2.6 mm Hg, respectively). No further complications (such as bleeding, embolism, delayed surgical treatment, rethrombosis) had occurred, and both patients became asymptomatic. After oral anticoagulation in a therapeutic INR range for 12 and 4 months, respectively, prosthetic heart valve function continued to be normal in both patients. Thrombolysis appears to be an efficacious and safe treatment in patients with thrombosis of a prosthetic cardiac valve in the pulmonary or tricuspid position, and it may be used as first-line therapy. Cinefluoroscopy is a simple and accurate method both in the diagnosis of prosthetic cardiac valve thrombosis and in following the response to thrombolytic treatment.

Characterization of valvular interstitial cell function in three dimensional matrix metalloproteinase degradable PEG hydrogels

Valvular interstitial cells (VICs) maintain functional heart valve structure and display transient fibroblast and myofibroblast properties. Most cell characterization studies have been performed on plastic dishes; while insightful, these systems are limited. Thus, a matrix metalloproteinase (MMP) degradable poly(ethylene glycol) (PEG) hydrogel system is proposed in this communication as a useful tool for characterizing VIC function in 3D. When encapsulated, VICs attained spread morphology, and proliferated and migrated as shown through real-time cell microscopy. Additionally, fibronectin derived pendant RGD was incorporated into the system to promote integrin binding. As RGD concentration increased from 0 to 2000 μ m, VIC process extension and integrin α vβ 3 binding increased within two days. By day 10, integrin binding was equalized between conditions. VIC morphology and rate of process extension were also increased through decreasing the hydrogel matrix density presented to the cells. VIC differentiation in response to exogenously delivered transforming growth factor-beta1 (TGF-β1) was also examined within the hydrogel networks. TGF-β1 increased expression of alpha smooth muscle actin (αSMA) and collagen-1 at both the mRNA and protein level by day 2 of culture, indicating myofibroblast differentiation, and was sustained over the course of the study (2 weeks). These studies demonstrate the utility, flexibility, and biological activity of this MMP-degradable system for the characterization of VICs, an important cell population for tissue engineering viable valve replacements and understanding valvular pathobiology.

Translating Autologous Heart Valve Tissue Engineering from Bench to Bed

Tissue engineering is currently being actively investigated to ascertain if it can offer an alternative to prosthetic aortic heart valves that may overcome the current limitations of prosthetic aortic heart valves while at the same time conferring the advantages of a living autologous structure, such as biocompatibility, the capacity to grow, repair, and remodel. In vitro studies have shown tissue-engineered heart valves to have adequate structural and functional properties, indicating a promising future for heart valve tissue engineering. However, criteria are required to be able to evaluate autologous heart valves and to deem them satisfactory for clinical use. Preclinical animal studies are needed, as a precursor to long-term in vivo follow-up studies, to establish such criteria. The first challenge is to find appropriate techniques to evaluate the functionality of tissue-engineered heart valves in vivo without having to kill the animal. As such, the development of such noninvasive techniques that are able to assess the functionality of tissue-engineered heart valves is the next step in translational research. This review discusses methods of evaluating the functionality of autologous heart valves when translating from in vitro to in vivo studies and determines potential assessment criteria imperative to achieve clinical applicability of tissue-engineered heart valves in aortic valve replacement.

Aspects scannographiques des prothèses valvulaires mécaniques aortiques et de leurs complications

Currently, multidetector row CT (MDCT) is routinely used for cardiac imaging, especially for detection of coronary artery disease and morphological and functional evaluation. Recent advances in MDCT with cardiac gating and improved spatial and temporal resolution allow non-invasive evaluation of cardiac valves with significant reduction in artifacts traditionally associated with valvular prostheses. Postsurgical follow-up of mechanical aortic valvular prostheses requires knowledge of the functioning mechanism of different valve types and related complications, some potentially lethal and sometimes of insidious onset. The most frequently used non-invasive imaging modalities to evaluate morphology and function of prosthetic heart valves are echocardiography and fluoroscopy. We present the CT imaging features of three mechanical aortic valvular prostheses and the value of CT for diagnosis of related complications as a complement to standard imaging modalities.