Heart valve structure: a predisposing factor for rheumatic heart disease.
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Adult↗
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[Anticoagulation in pregnant women after artificial heart valve replacement: is low-molecular-weight heparin an alternative?].
We report on the case of a 24-year-old pregnant woman with acute mechanical mitral valve thrombosis due to a treatment failure of low molecular weight heparin (LMWH) for permanent anticoagulation following mechanical valve replacement. Initially, our patient was put on oral warfarin for anticoagulation, but when her pregnancy was perceived the anticoagulation regimen was switched to daily subcutaneous administration of LMWH in order to minimize the risk of warfarin-induced embryopathy. During her 24th week of gestation she developed acute life-threatening pulmonary edema and hemodynamic instability, which was caused by an acute thrombosis of her artificial mitral valve. In an emergency operation the thrombozed valve was replaced by a porcine biological heart valve. The patient recovered uneventfully and gave birth to a healthy child in her 35th gestational week by cesarean section. In addition we discuss the rationale of different anticoagulation regimens with regard to maternal and fetal outcome with special consideration of LMWH as an alternative strategy to oral anticoagulation during pregnancy in women with mechanical heart valves.
Anticoagulants↗
Minimally invasive direct access heart valve surgery.
We review our experience with minimally invasive direct access (MIDA) heart valve surgery in 518 patients. Two hundred fifty-two patients underwent MIDA aortic valve replacement (AVR) or repair and 266 underwent MIDA mitral valve repair or replacement. Among the 250 AVRs, 157 (63%) were men, aged 63.2 +/- 14.6 years, NYHA functional Class 2.4 +/- 0.8. The surgical approach was right parasternal in 36 (14%) or upper hemisternotomy in 216 (86%). There were four (2%) operative deaths. Perioperative complications included 14 (5.6%) reexplorations for bleeding, 7 (3%) chest wound infections, 5 (2%) strokes, and 1 (0.4%) external iliac vein injury. Follow-up was complete in 193 (77%) patients, with a mean follow-up of 12 +/- 8 months. Late complications included 2 (0.8%) nonfatal myocardial infarctions, 4 (2%) reoperations for, respectively, 2 pericardial complications, 1 paravalvar leak, and 1 infected valve. There were five (2%) late deaths from congestive heart failure, pneumonia, hemorrhage, aneurysm, and cancer. Mean follow-up NYHA Class was 1.4 +/- 0.6. For the 266 mitral patients, 145 (54.5%) were men, age 58.7 +/- 13.6 years, functional Class 2.3 +/- 0.5. The surgical approach was right parasternal in 195 (73%), lower hemisternotomy in 53 (20%), right submammary thoracotomy in 9 (3.4%), or full sternotomy through a small skin incision in 9 (3.4%). There were 2 (0.8%) operative deaths. Perioperative complications included 4 (1.5%) reoperations for bleeding, 4 (1.5%) strokes, and 5 (2%) wound infections, and 3 (1%) ascending aortic complications. Follow-up was complete in 202 (76%) patients with a mean follow-up of 9.5 +/- 6.4 months. Late complications included one (0.4%) nonfatal myocardial infarction and three (1%) reoperations all converting repairs to replacements. There were three (1%) late deaths from suicide, pneumonia, and sudden death, respectively. Mean follow-up NYHA functional Class was 1.3 +/- 0.5. We conclude that MIDA heart valve surgery is safe and effective for the majority of patients requiring isolated elective aortic or mitral valve surgery.
Adolescent↗
A key to identify heart valve prostheses.
A system for the identification of heart valve prostheses has been developed. A series of observations is made on the structure of a prosthesis. Following each the most appropriate choice of two or three alternative findings is made. One is then directed to the next observation until a genus of prostheses is found with structural characteristics like the unknown one. Positive identification is aided by a brief description of each prosthesis in the genus.
Heart Valve Diseases↗
Tissue engineering of functional trileaflet heart valves from human marrow stromal cells.
BACKGROUND: We previously demonstrated the successful tissue engineering and implantation of functioning autologous heart valves based on vascular-derived cells. Human marrow stromal cells (MSC) exhibit the potential to differentiate into multiple cell-lineages and can be easily obtained clinically. The feasibility of creating tissue engineered heart valves (TEHV) from MSC as an alternative cell source, and the impact of a biomimetic in vitro environment on tissue differentiation was investigated. METHODS AND RESULTS: Human MSC were isolated, expanded in culture, and characterized by flow-cytometry and immunohistochemistry. Trileaflet heart valves fabricated from rapidly bioabsorbable polymers were seeded with MSC and grown in vitro in a pulsatile-flow-bioreactor. Morphological characterization included histology and electron microscopy (EM). Extracellular matrix (ECM)-formation was analyzed by immunohistochemistry, ECM protein content (collagen, glycosaminoglycan) and cell proliferation (DNA) were biochemically quantified. Biomechanical evaluation was performed using Instron(TM). In all valves synchronous opening and closing was observed in the bioreactor. Flow-cytometry of MSC pre-seeding was positive for ASMA, vimentin, negative for CD 31, LDL, CD 14. Histology of the TEHV-leaflets demonstrated viable tissue and ECM formation. EM demonstrated cell elements typical of viable, secretionally active myofibroblasts (actin/myosin filaments, collagen fibrils, elastin) and confluent, homogenous tissue surfaces. Collagen types I, III, ASMA, and vimentin were detected in the TEHV-leaflets. Mechanical properties of the TEHV-leaflets were comparable to native tissue. CONCLUSION: Generation of functional TEHV from human MSC was feasible utilizing a biomimetic in vitro environment. The neo-tissue showed morphological features and mechanical properties of human native-heart-valve tissue. The human MSC demonstrated characteristics of myofibroblast differentiation.
Absorbable Implants↗
Pressure and flow fields in the hinge region of bileaflet mechanical heart valves.
BACKGROUND AND AIM OF THE STUDY: Recent clinical thrombotic experiences with the Medtronic Parallel (MP) bileaflet heart valve have highlighted the need for new methods to assess preclinical valve hinge flow. The aim of the current study was to investigate hinge pivot flow fields in bileaflet mechanical heart valves using flow visualization in scaled x5 magnification transparent polymer models and computational fluid dynamic (CFD) analysis using CFD 2000 STORM code. METHODS: Polymeric x5 flow models of the On-X, St. Jude Medical (SJM) and MP bileaflet heart valves were constructed using laser stereolithography to replicate the interior geometry while maintaining realistic manufacturing tolerances. Each hinge flow experiment was carried out by installing the transparent x5 model in a pulsatile flow loop, which was designed according to Womersley number similitude requirements. Motions of suspended microparticles in the valve hinge area, recorded by laser imaging techniques, were used to visualize hinge flow. Experimentally measured parameters were used as input for CFD analysis. CFD simulations were made by solving the Navier-Stokes equation using a finite volume method with the pressure-based algorithm for continuity, and a pressure-implicit with splitting of operators (PISO) algorithm for pressure-velocity coupling. Moving grid methodology was employed to simulate periodic motion of the valve leaflets. CFD hinge flow results were visualized on four parallel planes at different depths in the hinge socket. The hinge flow patterns of the three types of bileaflet heart valve design are discussed. RESULTS: Prominent vortex formation and stagnant flow areas were noticed in the pivot region of the MP valve. Vortices persisted throughout both the forward- and reverse-flow phases. These flow structures were not observed in the hinge areas of the SJM and On-X valves. CONCLUSIONS: Vortex formation observed in the MP valve may contribute to the high thrombogenic potential of this valve. The absence of such vortices and areas of stagnant flow in the On-X and SJM valves indicate that hinge flow conditions in these valves do not favor mechanically induced thrombogenesis or thromboembolic events.
Biocompatible Materials↗
Lack of association between factor V Leiden and thromboembolism in patients with prosthetic heart valves.
Thromboembolism represents the most serious complication in patients with prosthetic heart valves, and causes significant mortality and morbidity. Many risk factors for the condition have been identified. However, many patients who have a therapeutic level of anticoagulation and no obvious risk factors develop thromboembolism. Factor V Leiden, found in 3-7% of the normal population, is the most common inherited factor associated with thrombosis. Whether or not this factor is associated with thromboembolism in this setting has not been explored. This study compares the prevalence of factor V Leiden in patients with prosthetic heart valves, with and without thromboembolic complications. A total of 148 patients were studied. Thirty had documented thromboembolic complications and none exhibited the factor V mutation. Of the 118 patients without thromboembolic complications, seven (5.9%) were heterozygous for factor V Leiden (P = 0.345, by Fisher's two-tailed exact test; odds ratio 0, 95% confidence interval 0.0-4.34). We conclude that until future data shows otherwise, routine testing for factor V Leiden in patients with prosthetic heart valves is not warranted, except as part of ongoing research.
Bioprosthesis↗
Numerical simulation of mechanical mitral heart valve closure.
A computational fluid dynamic simulation of a mechanical heart valve closing dynamics in the mitral position was performed in order to delineate the fluid induced stresses in the closing phase. The pressure and shear stress fields in the clearance region and near the inflow (atrial) side of the valve were computed during the mitral heart valve closure. Three separate numerical simulations were performed. The atrial chamber pressure was assumed to be zero in all the simulations. The first simulation was steady flow through a closed mitral valve with a ventricular pressure of 100 mm Hg (1.3 kPa). In the second simulation, the leaflet remained in the closed position while the ventricular pressure increased from 0 to 100 mm Hg at a rate of 2000 mm Hg/s (simulating leaflet closure by gravity before the ventricular pressure rise - gravity closure). In the third case, the leaflet motion from the fully open position to the fully closed position was simulated for the same ventricular pressure rise (simulating the normal closure of the mechanical valve). Normal closure (including leaflet motion towards closure, and sudden stop in the closed position) resulted in a relatively large negative pressure transient which was not present in the gravity closure simulation. The wall shear stresses near the housing and the leaflet edge close to the inflow side were around 4000 Pa with normal closure compared to about 725 Pa with gravity closure. The large negative pressure transients and significant increase in wall shear stresses due to the simulation of normal closure of the mechanical valve is consistent with the previously reported increased blood damage during the closing phase.
Biomedical Engineering↗
Further evidence of gaseous embolic material in patients with artificial heart valves.
OBJECTIVE: We undertook this study to evaluate the hypothesis that most microemboli signals in patients with artificial heart valves are gaseous, assuming that microemboli counts in cerebral arteries would progressively decline with increasing distance from the generating heart valve. METHODS: A total of 10 outpatients with CarboMedics (Sulzer Carbomedics Inc., n = 5) and ATS prosthetic heart valves (n = 5) in the aortic (n = 8), mitral (n = 1), or both aortic and mitral positions (n = 1) were recruited. Monitoring was performed simultaneously over the middle and anterior cerebral arteries and the common carotid artery for 30 minutes with the 2 MHZ transducers of a color duplex scanner (common carotid artery) and pulsed-wave Doppler ultrasonography (intracranial arteries). All data were harvested in an eight-channel digital audio tape recorder, and microembolic signal counts were evaluated online by two separate observers. RESULTS: Significantly higher microembolic signal counts were recorded in the common carotid artery (112 [75 to 175]) compared with the middle and anterior cerebral arteries (30 [18 to 36], p < 0.0001). Interobserver variability was satisfactory (k = 0.81). CONCLUSIONS: Our results strongly argue for gaseous underlying embolic material in patients with artificial heart valves because bubbles are bound to implode with time.
Adult↗
Expression of endothelial cell adhesion molecules on heart valves: up-regulation in degeneration as well as acute endocarditis.
Inflammatory cytokines such as interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF-alpha), as well as shear stress, cause endothelial cells (ECs), to undergo not only functional alterations but also structural reorganizations, which contribute to vascular leakage. Like ECs of the human aorta, ECs on heart valves are exposed to extreme shear stress. However, while ECs expression of cell adhesion molecules (CAMs) in large vessels has been widely studied, it seems that there are no such studies on ECs of heart valves, although this knowledge might be important for our understanding of the aetiological aspects of local inflammatory responses. Using immunohistochemistry, this study characterized the CAM expression of ECs on degenerative, mostly calcified heart valves and on heart valves with florid endocarditis. As expected, the constitutively expressed molecules (ICAM-1, CD34, CD31) were found both on degenerative and on inflamed valves. Furthermore, marked expression of E-selectin and VCAM-1 was found not only on inflamed valves, but also on larger portions of the degenerative valves with no morphological evidence of inflammation. This striking finding might help to explain why patients with fibrotic heart valves are susceptible to recurrent endocarditis. Why the endothelial activation markers E-selectin and VCAM-1 are expressed on degenerative heart valves requires further investigation.
Acute Disease↗
Quality control of bioprosthetic heart valves by means of holographic interferometry.
BACKGROUND AND AIMS OF THE STUDY: Limited durability of porcine bioprostheses is mainly caused by the progressive development of calcification. We tested the hypothesis that hidden tissue anomalies or unfavorable stress concentrations of commercially available bioprostheses may lead to later calcification and dysfunction. Application of holographic interferometry for non-destructive testing of biological heart valves enables a full-field analysis of heart valves and reveals deformation irregularities of valve tissue. MATERIAL AND METHODS: We developed an accelerated calcification protocol for bioprosthetic heart valves including an accelerated pulsatile valve tester for simultaneous testing of 10 heart valves under identical conditions and a rapid synthetic calcification fluid containing a final Ca x P of 130 (mg/dl)2 in barbital buffer solution. Ten porcine bioprostheses (St. Jude Medical, Bioimplant) were assessed by holographic interferometry and subjected to the pulsatile accelerated calcification process. Distribution and amount of calcification was evaluated by microradiography after 12 x 10(6) and 19 x 10(6) cycles, respectively. Areas of irregular fringe patterns detected by holography as well as areas of calcification were calculated and compared using a personal computer. RESULTS: All tested bioprostheses had localized or extended areas with holographic irregularities and the accelerated valve testing protocol resulted in even macroscopically visible calcifications at various sites. Comparative analysis of the obtained microradiographs revealed that 74.2% +/- 6.0% of calcified leaflet areas lay within the previously detected holographic anomalies. CONCLUSIONS: Our first results show a strong correlation between holographic anomalies and calcification of porcine bioprostheses. We conclude that suitable methods for evaluation and quality control of bioprosthetic heart valves are available and seem to be predictive with regard to valve calcification.
Aortic Valve↗
Modification of the Gorlin equation for use with heart valve substitutes.
The Gorlin equation, which was used to assess the obstruction to flow by a stenosed heart valve, is based on steady flow (time independent) criteria derived from hydraulics. Recently, this equation has been used to obtain an effective orifice area for heart valve substitutes both in vitro and in vivo. In this study, a modification of the original Gorlin equation for use with heart valve substitutes considers both the pulsatility of the valvar flow and possible variations in volumetric flow waveforms induced by differences in myocardial performance. The modified equation also allows for the possibility of regurgitant flows. Its use is illustrated in a study of the hydrodynamic performance of a series of heart valve substitutes and recommendations are made concerning its application to cardiac catheterisation procedures.
Blood Flow Velocity↗
[Double heart valve replacement disclosing antiphospholipid syndrome].
In patients with systemic lupus erythematosus (SLE) heart valve lesions are usually discovered at echocardiography; their haemodynamic repercussions are uncommon, and valve replacement is exceptional. We report the case of a woman who had undergone aortic and mitral valve replacement before antiphospholipid antibodies were found associated with 4 ARA criteria of SLE. Histopathological examination confirmed the diagnosis of Libman-Sachs specific endocarditis. The presence of antiphospholipid antibodies leads to a discussion of their role in the physiopathology of the heart valve lesions and vascular accidents that occurred in this patient. The overlap observed between the diagnostic criteria of SLE and those of primary antiphospholipid syndrome is discussed. Heart valve lesions may be one of the modes of access to the antiphospholipid syndrome.
Adult↗
Gas bubble emboli detected by transcranial Doppler sonography in patients with prosthetic heart valves: a preliminary report.
After observing spikes in the Doppler signal of cerebral arteries of patients with neurologic symptoms and prosthetic heart valves, we then studied two groups of patients with prosthetic heart valves: seven patients with neurologic symptoms and 65 asymptomatic patients. Using transcranial Doppler sonography of the middle cerebral artery, we found Doppler spikes in six symptomatic and 24 asymptomatic patients with mechanical heart valves. No spikes were found in one symptomatic and 21 asymptomatic patients with biological valves or in 20 asymptomatic patients with mechanical valves. We concluded that gas cavitation during the opening or closure of the valve, producing bubble emboli, is the most probable explanation for these Doppler spikes in patients with mechanical prosthetic heart valves.
Aged↗
Integrating particle image velocimetry and laser Doppler velocimetry measurements of the regurgitant flow field past mechanical heart valves.
This study investigates the transient regurgitant flow downstream of a prosthetic heart valve using both laser Doppler velocimetry (LDV) and particle image velocimetry (PIV). Until now, LDV has been the more commonly used tool in investigating the flow characteristics associated with mechanical heart valves. The LDV technique allows point-by-point velocity measurements and provides enough information about the temporal variations in the flow. The main drawback of this technique is the time consuming nature of the data acquisition process in order to assess an entire flow field area. The PIV technique, on the other hand, allows measurement of the entire flow field in space in a plane at a given instant. In this study, PIV with spatial resolution of 0 (1 mm) and LDV with a temporal resolution of 0 (1 ms) were used to measure the regurgitant flow proximal to the Björk-Shiley monostrut (BSM) valve in the mitral position. With PIV, the ability to measure 2 velocity components over an entire plane simultaneously provides a very different insight into the flow field compared to a more traditional point-to-point technique like LDV. In this study, a picture of the effects of occluder motion on the fluid flow in the atrial chamber is interpreted using an integration of PIV and LDV measurements. Specifically, fluid velocities in excess of 3.0 m/s were recorded in the pressure-driven jet during valve closure, and a 1.5 m/s sustained regurgitant jet was observed on the minor orifice side. Additionally, the effects of the impact and subsequent rebound of the occluder on the flow also were clearly recorded in spatial and temporal detail by the PIV and LDV measurements, respectively. The PIV results provide a visually intuitive way of interpreting the flow while the LDV data explore the temporal variations and trends in detail. This analysis is an integrated flow description of the effects of valve closure and leakage on the pulsatile regurgitation flow field past a tilting-disc mechanical heart valve (MHV). It further reinforces the hypothesis that the planar flow visualization techniques, when integrated with traditional point-to point techniques, provide significantly more insight into the complex pulsatile flow past MHVs.
Blood Flow Velocity↗
A novel technique in a sheep model for evaluating prosthetic heart valve performance.
There have been many various animal studies to evaluate the structural integrity and antithrombogenicity of prosthetic heart valves. We were interested in developing a novel sheep model to study the thrombogenicity of mechanical heart valves placed into the systemic circulation but without the need for cardiac bypass. Also, we wanted to minimize the risk ofparaplegia from complete thoracic aortic clamping. Six sheep underwent left lateral thoracotomy for placement of a mechanical heart valve in parallel with the descending thoracic aorta. A valved conduit with a dacron tube graft sutured to the back end was fashioned. Employing partial aortic occlusion with a side-biting clamp, the proximal and distal ends were anastomosed in an end-to-side fashion. Once flow was confirmed through the graft, the native aorta was occulded with umbilical tape. The sheep received no postoperative anticoagulation. The median operative time and estimated blood loss (EBL) was 170 min and 250 cc, respectively. Patency of the valved conduits was confirmed during the initial procedure, and there was no incidence of paraplegia postoperatively. Two animals expired shortly after extubation and at necropsy the valved conduits were patent with preserved valve function. The four survivors were sacrificed a median of 37 days postoperatively. Prior to euthanasia, the valved conduits were evaluated in situ with ultrasound. In all cases, the valves had clot formation at the hinges, which prevented active movement of the leaflets. This novel in vivo technique provides an alternative in testing the thrombogenicity of prosthetic heart valves without cardiac bypass or the risk of paraplegia in an animal that is extremely sensitive to complete aortic cross-clamp.
Anastomosis, Surgical↗
Age-related complications and optimal choice of artificial heart valves in elderly patients.
The use of bioprosthetic heart valves in elderly patients is presently advocated by many since implanting mechanical valves are considered to result in unacceptable rates of thromboembolism and bleeding. However the somewhat limited durability of bioprostheses has to be acknowledged since a group of elderly patients will eventually require a reoperation due to tissue failure. We have evaluated our policy to implant mechanical heart valve prostheses even in elderly patients based on the conception that we believe that anticoagulation in this group of patients can be handled with a low rate of complications.
Age Factors↗
A collagen-glycosaminoglycan co-culture model for heart valve tissue engineering applications.
In order to develop efficient design strategies for a tissue-engineered heart valve, in vivo and in vitro models of valvular structure and cellular function require extensive characterisation. Collagen and glycosaminoglycans (GAGs) provide unique functional characteristics to the heart valve structure. In the current study, type I collagen-GAG hydrogels were investigated as biomaterials for the creation of mitral valve tissue. Porcine mitral valve interstitial cells (VICs) and endothelial cells (VECs) were isolated and co-cultured for 4 weeks in hydrogel constructs composed of type I collagen. The metabolic activity and tissue organisation of mitral valve tissue constructs was evaluated in the presence and absence of chondroitin sulphate (CS) GAG, and comparisons were made with normal mitral valve tissue. Both collagen and collagen-CS mitral valve constructs contracted to form tissue-like structures in vitro. Biochemical assay demonstrated that over 75% of CS was retained within collagen-CS constructs. Morphological examination demonstrated enhanced VEC surface coverage in collagen-CS constructs compared to collagen constructs. Ultrastructural analysis revealed basement membrane synthesis and cell junction formation by construct VECs, with an increased matrix porosity observed in collagen-CS constructs. Immunohistochemical analyses demonstrated enhanced extracellular matrix production in collagen-CS constructs, including expression of elastin and laminin by VICs. Both native valve and collagen-CS construct VECs also expressed the vasoactive molecule, eNOS, which was absent from collagen construct VECs. The present study demonstrates that collagen gels can be used as matrices for the in vitro synthesis of tissue structures resembling mitral valve tissue. Addition of CS resulting in a more porous model was shown to positively influence the bioactivity of seeded valve cells and tissue remodelling. Collagen-GAG matrices may hold promise for a potential use in heart valve tissue engineering and improved understanding of heart valve biology.
Animals↗