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ARTIFICIAL HEART VALVES
Aysel KIZILTAY, 24.05.2000
Anatomy
The heart has four chambers. The upper two are the right and left atria; the lower two, the right and left ventricles. Blood is pumped through the chambers, aided by four heart valves. The valves open and close to let the blood flow in only one direction.(Fig1)[1]
Fig1
What are the four heart valves?
· The tricuspid valve is located between the right atrium and right ventricle.
· The pulmonary or pulmonic valve is between the right ventricle and the pulmonary artery
· The mitral valve is between the left atrium and left ventricle.
· The aortic valve is between the left ventricle and the aorta.(Fig2)
Each valve has a set of leaflets(also called cusps). When working properly, the heart valves open and close fully. opening and closing of bileaflets each occur in less than 35ms. For a heart rate of 75 beats per minutes, systole typically lasts for around 270ms of the 800ms pulse period. Therefore an aortic valve is fully open for at least 74% of its forward flow phase, and a mitral valve for at least 87%.
Fig2
What is a defective heart valve?
A defective heart valve is one that fails either to close or to open fully.
*The most commonly replaced valves are the mitral and aortic valves.
How Heart Valves Fail
Complications and diseases of heart valves fall under four major categorie[2]
Stenosis:
Stenosis is the obstruction of blood flow across a heart valve. Rheumatic, degenerative calcification, and congenital defects are the three causes of stenosis. Rheumatic fever is an infection of the respiratory tract spreads to the heart causing the cusps of a valve to fuse together. Calcification is the accumulation of deposits on the valve and often causes the cusps to harden.
Mitral Valve Prolapse:
Mitral valve prolapse is the most common form of valvular heart disease. Prolapse is the inflammation of the tendinae, the tendons attached to the mitral valve that assist in opening and closing the valve. Prolapse-- an incomplete closing of thew mitral valve, which causes regurgitation.
Regurgitation:
Regurgitation is the flow of blood opposite its intended direction and is mainly due the incomplete closing of valve due to calcification, prolapse, stenosis, and congenital defects.
Congenital Defects:
Congenital valve defects are the malformation or disease of valves at birth. 32000 babies are born each year with congenital heart disease.
Every year, thousands of patients around the world are in needed of cardiac surgery to replace their diseased, damaged, or malfunctioning hear valves. There are several types of artificial heart valves available for this purpose. Each type has its own unique advantages and disadvantages. [3]
Prosthetic Heart Valves
The ideal heart valve would have a number of characteristics:
· Easily surgically placed
· Adaptable to the natural motion of the heart
· Present little to no resistance to the bodies immune system
· Allow smooth flow across the valve
· Prevent regurgitation
· Hemodynamically competent
· Nonobstructive
· Cause minimal damage to blood elements
· Be durable
· Completely reliable
· Not annoy the patient with noise
· Withstand chest nuggies
Currently Available Valves
All current cardiac valves lack of some of the criteria for an ideal prosthesis. Therefore, specific patient needs must be matched to the attributes of a particular valve. There are essentially two classes of valve substitutes available at present: the bioprosthetic glutareldhyde-preserved valve and the mechanical valve.[4,5,15]
Bioprosthetic Valves:
One type of valve replacement are bioprotheses that are organic valves. They include porcine(pig) and valves as well as homograft and allograft valves which are grafted from humans. The advantages of these are their hemodynamics, which are very similar to human valves, and their lack of anticoagulant use. Human valves include a high risk risk of calcification in younger patients. The major disadvantage is their lack of long term durability, especially in younger patients, which is why many who are looking for a long lasting valve replacement choose mechanical valve.
Mechanical Valves:
Mechanical valves were invented by the need for a long lasting valve with reduced risks of calcification-- successful prosthetic valve replacement occurred in 1960 with an open caged-ball valve. This valve offers dependable alternative to bioprostheses but still produced calcification around the valve. This brought a tilting-disc valve in 1967 followed by the bileaflet in 1976, which is the most popular valve used today.
These valves had structural and mechanical durability, they have a life expectancy of 5-6 years and often a decade. However with prosthetic valves include lifelong use of anticoagulants and the risk of calcification --these disadvantages, their durability accounts for their popularity over bioprostheses.
Tissue( bioprosthetic) Valves
The development of an ideal heart valve substitute remains the goal of many researchers. Bioprosthetic valves, such as those prepared using bovine pericardium or aortic valve offer good flow characteristics but are ultimately limited by durability, failure often being accelerated by calcification and fatigue. Patterns of calcification in this type of valve have been established using in vitro techniques and have been shown to relate to mechanical factors. In addition mechanisms of calcification and failure have been linked to repetitive bending stress in the leaflets. A new technique, laser profiling, which provides high resolution data on the motion of flexible leaflet heart valves, have been developed for use as a tool in the design of this type of prosthesis. The laser profiling technique was able to reveal changes in the functional dynamics of pericardial valve leaflets not otherwise detectable by convential (hydrodynamic) measurements of valve performance[6]
The search for a noncalcifying tissue material to be used for valve replacement application continues to be a field of extensive investigation.
Biopolymers which developed mainly for cardiovascular prosthetic devices are essentially collagen derivatives of animals; crosslinked by glutareldhyde or other agents in order to improve their mechanical properties and to depress their immunogenecity[7]
Calcification of Bioprosthetic Heart Valves
Calcification defined as the deposition of calcium compounds such as either some calcium phosphate minerals consisting of hydroxyapatite or calcium salts, results in the loss of biomaterial flexibility thereby causing their mechanical failure and degradation.
Cardiovascular calcification, the formation of calcium phosphate deposits on cardiovascular tissue is a common end-stage phenomenon affecting a wide variety of bioprostheses. Cuspal mineralization, however, is a significant limitation to their long term success with calcification accounting for over 60% of failures. Several factors for tissue-associated calcification have been identified. The most important host factor is young age, and the chief implant factors include glutateraldehyde treatment, material stress, adsorption of calcium-binding proteins, surface porosity and water contented surface-adhered cellular debris. the exact mechanisms of bioprosthesis associated calcification leading to implant failure are not well understood and there is not effective therapy.
Calcific degeneration of glutaraldehyde-pretreated bioprosthetic heart valves (Fig3) is the most important example of a clinically significant dysfunction of a medical device due to biomaterial calcification. Glutareldehyde-preserved (i.e.crosslinked) stent-mounted bioprostheses fabricated from porcine aortic valve, or bovine pericardial tissue, have been implanted in hundreds of thousands of patients since 1971. Howver, more than half of such valves implanted in patients fail within 12-15 years.[3,5]. Nearly all bioprosthetic valves retrieved at reoparation have tears or stiffening, or both resulting from intrinsic calcification. Furthermore accelerated mineral accumulation leading to valve failure in less than 4 years is almost uniform in adolescent and preadolescent children with bioprostheses. Calcification is most pronounced at the flexure regions of the cusps, the points of greatest functional valve stresses.
Homograft valves are valves that are removed from a person who has died, and then are sterilized, often further preserved, and implanted in another individual. A homograft aortic valve is surrounded by a sleeve of aorta. Many homografts, whether
Fig3
containing aortic valves or nonvalved (to replace a large blood vessel), undergo calcification and/or degeneration in the aortic wall.
In general, the determinants of biomaterial minerilazation includes factors related to both host metabolism and implant structure and chemistry.
Two major approaches to reduce the calcification of tissue prosthesis have been attempted: first; implant modification to prevent calcification by preventing surfaces with various agents such as diphosphonates, sodium doddery sulphate, protamine sulphate, aluminum and ferric ions, 2-amino oleic acid or grafting polyethylene glycols and second; local polymeric delivery of some of these agents. Further in a recent publication have reported that ethanol preincubation of glutaraldehyde-crosslinked porcine aortic valve bioprosthesis is a highly efficacious treatment for preventing calcification. However there is no completely satisfactory method that is currently available for preventing calcification.
Calcification process [8] in living organisms are always driven by an organic matrix mainly made of proteins which aggregate with lipids and polysaccharides form templates where salt precipitations can take place in an ordered manner. Furthermore, proteins and lipids are able adsorb onto biomaterial surfaces during the early phase implant affecting the biocompatibility of these protheses. It is known that fibrinogen adsorption mediates platelet adhesion and is a major factor in clot formation. Albumin-coated surfaces have, however been shown to inhibit fibrinogen binding and reduce platelet adhesion.
Albumin and gelatin are being widely used for modifying polymeric substrates to improve their bloodcompatability because of their passive role in platelet attachment.
Earlier studies indicated that immobilization of various bioactive molecules like urokinase, PGG1, PGI2, heparin, antithrombin etc. on albuminated polymeric interfaces can substantially improve their blood compatibility. However the effect of such surface modifications on bioprosthetic interfaces and their subsequent calcification profile are not well understood.
In recent studies it is reported that Ca2+ is required for most forms of platelet aggregation, and it is believed that cyclic adenosine monophosphate (cAMP) functions in platelets by directing the uptake of calcium. Therefore in increase in cAMP may inhibit platelet responsiveness. Most antiplatelet agents, including PGE1 and PGI2, inhibit platelet activity via increasing cAMP, a mediator of cell functions.
The immobilization of various bioactive molecules, such as PGE1, PGI2 and heparin on albumin modified glutaraldehyde-treated porcine pericardium. These antiplatelets can modify the pericardial surfaces and subsequently their interaction with blood components and the minerilazation process.
The calcification profile of these tissues was in the order: GAPP> Alb-GAPP>albGAPP-PGI2>Alb-GAPP-Hep> Alb-GAPP-PGE1> Alb-GAPP-Hep-PGE1
In other words, higher inhibitory effects on tissuecalcificatiob were observed due to surface modifications with antiplatelet agents, on exposure to calcium phosphate solution.
The long term durability of xenograft heart valves is limited due to calcification of the tissue, which leads to stiffening, tearing and rupture of cusp.
Porcine heart valves are often considered for heart replacement in elderly patients. To reduce immunogenecity and degradation, the porcine tissue is crosslinked with glutareldhyde (GA). Furthermore in the fabrication process a stent is added to simplfy implantation[9,10]
To reduce the occurrence of calcification alternative crosslinking methods are investigated.
Factors affecting Succes of thrombolytic therapy
· Valve position: Aortic more successful, mitral less successful.
· Valve type : St. Jude bileaflet more successful, ball and single leaflet less successful
· Amount of clot present: Large amount of clot lowers success rate
Factors increasing risk of thrombolytic therapy:
· Greater amount of clot
· Mitral position: Higher risk of embolism
· Single leaflet or ball valve: Higher risk of embolism
Mechanical Heart Valves
Mechanical cardiac valvular prostheses currently enjoy a 60% to 40% market-share advantage over tissue prosthesis in the USA and worldwide. Only the Starr Edwards caged silastic ball, Medtronic Hall, St. Jude Medical and Omniscience valves remain available in the united states.
History: During the 1970s, bioprosthetic heart valves enjoyed a rapid growth in popularity because, in addition to providing the cardiac surgeon with the ability to directly treat valvular lesions, they offered the potential of decreased risks of some valve-related complications during follow-up. The mood among cardiac surgeons swung to favor bioprostheses, with the focus being primarily on the diminution of late valve-related events at the potential cost of decreased durability.
In the early 1980s, the decreased durability of bioprostheses became established fact, and fickle cardiac surgeons shifted their mood pendulum back to durability preoccupations over concerns for late thromboembolic events. One reason was that second-generation mechanical valves offered new design features with projected clower thromboembolic rates without loss of durability.
More recently, the durability of some of the newer designed mechanical valves has come into question, particularly the convexoconcave version of the Björk-Shiley valve and the Duramedics valve, prompting their withdrawal from the market[11]
Mechanical heart valve market
The most popular prosthetic valves are:
*Bjork-Shiley Convexo-Concave
Bjork-Shiley Monostrut
*Starr-Edwards ball
Starr-Edwards disc
Starr-Edwards caged Silastic(Dow corning) ball
Carbomedics
Medtronic-Hall (single leaflet)
St. Jude (bileaflet)
ATS Medical
Omniscience
The Bjork-Shiley valve is one of the most successful single disc valves ever made. The original model of the B-S valve was an extremely reliable and durable valve. It had good hemodynamics and a low rate of thromboembolism. The B-S valve is a tilting disk valve with a single disk The disk is held in place by an inflow and out flow strut. Certain models of B-S valve developed strut fractures resulting in embolism of the disk. This led to all models of the B-S valve being removed from the United States. Curently the Bjork-Shiley monostrut model is still salled in Europe and outside the USA.
Only the Starr-Edwards
Studies with mechanical heart valves
In a review Cary W. et al [11] studied follow-up about four mechanical heart valves which remain available in the United States:
The Starr-Edwards models 1260 and 6120 valves are ball-cage prostheses with a barium-impregnated silastic (Dow corning) ball riding inside a stellite cage to which is attached a seamless cloth sewing ring. The ball is removable from the aortic prosthesis but not from mitral prosthesis.
The Medtronic -Hall valve is a single tilting-disc prosthesis with a circular disc coated with pyrolytic carbon, which pivots over a central strut inside a housing machined from one solid piece of titanium to which is attached a teflon sewing ring. The aortic valve is designed to have an open-disc angle of 75 degrees, and the mitral disc angle is 70 degrees.
The St. Jude Medical valve is a bileaflet prosthesis whose pyrolytic carbon discs pivot inside a pyrolytic carbon housing to which is attached a Dacron sewing ring. The two leaflets of the St. Jude valve open to 85 degrees from the horizontal axis.
The Omniscience valve is a second-generation design of the original Lillehei-Kaster valve with a single pyrolytic carbon disc inside a titanium housing to which is attached a seamless Teflon sewing ring. The disc is designed to open to an angle of 80 degrees.
Table 1 Mechanical Valve Characteristics |
Characteristic |
S-E |
M-H |
SJM |
OS |
Stuctural integrity |
4+ |
4+ |
3+ |
4+ |
Profile |
1+ |
3+ |
4+ |
3+ |
Ability to rotate |
0 |
4+ |
0 |
4+ |
Freedom from occluder impingement |
|
|
3+ |
2+ |
Low gradient |
3+ |
4+ |
4+ |
3+ |
Complete opening |
3+ |
4+ |
4+ |
2+ |
Dynamic regurgitant fraction |
3+ |
3+ |
4+ |
4+ |
Static leak rate |
4+ |
3+ |
2+ |
3+ |
A grade of 4+ is the best and 0, the worst [11]
Despite the requirement of anticoagulation, mechanical valve prostheses offer the advantage of proven durability. The long-term results of 467 aortic valve replacement and 342 mitral valve replacement using the Starr-Edwards prosthesis with 110 aortic valve replacements and 105 mitral valve replacements using the Björk-Shiley prosthesis. Long term survival with mean follow-up over 5 year was not significantly different between respective groups. The probability of thromboembolic complications, however was significantly higher with the S-E prosthesis in both the aortic and mitral positions. The probability of valve failure although low for all groups, was significantly higher in the B-S mitral group due to late thrombotic occlusion. Use of the S-E and B-S prostheses is associated with satisfactory functional improvement and similar long-term survival rate. However, the increases risk of valve failure due to late thrombotic occlusion of the B-S prostheses should be considered when choosing a mechanical mitral valve[12]
All patients received sodium warfarin anticoagulation beginning on the second postoperative day, and this was continued indefinitely. Postoperative heparin therapy was not routinely employed. The post operative mortality was higher for the Bjork-Shiley patients than the for Starr-Edwards patients in both the aortic(% versus 6%) and the mitral (14% versus 10%) positions. Increased risk of mortality associated with:
· older age
· the performance of coronary artery bypass grafts
· male sex
In the mitral positiontherewas a significant difference with a higher probability of valve failure with the Bjork-Shiley prostheses This higher probability wascclearly related to the occurrence of late thrombotic occlusion of this prosthesis in the mitral position. Thrombotic occlusion of prostheses was observed in all four valve groups.
A major advantage of porcine or pericardial tissue valves is freedom from long-term anticoagulation. However, because of the unproven durability of these valves, especially in young patients, and the need for reasons unrelated to prosthesis type, there continues to be considerable use of mechanical prostheses.
The 2 popular mechanical valves, the Starr-Edwards ball-valve prosthesis and Bjork-Shiley tilting disk prosthesis, differ with regard to several charecteristics. The S-E valve by virtue of its prominent cage design, can not always be used in the patient with the small aortic root or small ventricular cavity. By contrast the B-S valve with its low profile, functions well in the small heart aorta. The B-S rosthesis functions with lower transvalvular gradients than the S-E valve in both the aortic and mitral position; however both prostheses result in satisfactory functional improvement and offer durability. Unfortunately, despite long-term anticoagulant therapy, both prostheses are associated wih thromboembolic complications.
Bileaflet Prosthesis
Bileaflet heart valve are currently the most commonly implanted type of mechanical valve, because of their low transvalvular pressure drop, centralized flow and durability.
Althogouh the flow performance of bileaflet heart valves is generally superior to alternative mechanical heart valve designs, problems remain with blood clotting of the valve site. A clot at the valve may either obstruct the valve motion or result in thromboembolism. To prevent such problems patients are required to receive life-long anticoagulation drug therapy.
Blood clotting depends on the interaction of blood biochemistry, the blood-conducting material surface and the blood flow. Thromoembolic complications associated with mechanical heart valves have been greatly reduced by the use of improved materials particularly pyrolytic carbon[13,14].Si-alloyed pyrolytic carbon(Pyc) is currently employed in many biomedical devices due to its fairly good biological compatibility and nonbiodegredability.
On the flow side, elevated blood shear stresses and regions of persistent blood recirculation are both associated with thrombus formation, particularly when the two effects occur in combination. All prosthetic valves are believed to cause some blood shear damage[15]. Whilst cavities in the valve pivot region can provide regions where blood recirculates without being washed into the main bloodstream. Although some valve designs attempt to use the leaflet motion to ‘sweep out’ the pivot cavities, the sweeping will become less effective as the material surface begin to degenerate in the hostile biological environment.[13]
The ATS bileaflet valve (ATS Medical Inc.,Minneapolis, USA) incorporates a new design of leaflet pivot, compared to previous bileaflet designs. This design ensures that the ATS valve has no cavities, where persistent recirculating flow may occur. Initial clinical results with the ATS valve have shown a promisingly loww incidence of thromboembolism. In a comperative in vitro study the ATS valve also showed the lowest transvalvular pressure drop under pulsatile flow conditions.
Since the first successful use of prosthetic heart valves for treatment of valvular heart diseases many varieties of valve prosthesis design have been developed. Bileaflet prostheses are now most commonly used[16]. The St. Jude Medical Valve prosthesis(SJ) (St. Jude Medical, Inc, St.Paul.. In. USA) was first used clinically in 1977. The Carbomedics prosthetic heart valve(CM) (Carbomedics, Inc., Austin, TX, USA) was first introduced into clinical use in 1986. Both the Cm and SJ arelow-profile bileflet prostheses with pyrolytic carbon constructing the leaflets and orifice. Yet there were some differences between these two valves. For example, each leaflet opens to 85 degrees with a travel arc of 55 degrees in sizes 27-33mm of SJ and opening angle of80 degrees with travel arc of 55 degrees in all sizes of CM. Both Sj and CM were reported to have favorable hemodynamic performance and clinical results.
Anticoagulant therapy
Prosthetic valve thrombosis is a life threatening complication after valve replacement. Both tissue valves and mechanical valves can develop thrombosis, but it is much more common for mechanical valves to develop obstructive thrombus than tissue valves. Consequently the literature on thrombolytic therapy for valve thrombosis has focused almost entirely on mechanical valves.
The achieving target dose of warfarin is 3.0 to 4.0 mg to get optimal anticoagulation therapy is recommended to minimize the complications of anticoagulation-related hemorrhage . In Asian people because of their the less thrombogenic character lower dose can be used.
Thrombotic complications also related to the patient’s conditions, including atrial fibrillation, varying left atrial size, and compliance with anticoagulation.
Some Charecteristics ofMechanical Heart Valves
Prosthetic Design: A correct fluid dynamic design of artificial heart valve prostheses in order to avoid or limit phenomeno such as vortices, stagnation, reecurcilation and high velocity gradients which may lead to thrombus formation and hemolysis.
Hemolysis: Hemolytic and subhemolytic blood damage by mechanical heart valve prostheses have been observed in both clinical and in vitro investigations[15].
Mechanical heart of recent design do not cause severe hemolysis if they operate correctly. However the nonphysiological flow may damage or destroy the blood cells. This is indicated by an increased plasma hemoglobin,shortened red cell survival, increased reticulosyte counts, loss of deformability. The hemolytic capability depends on the type of valves used.(mechanical load). only a few in vitro studies reported about valve induced hemolysis. For this purpose blood-filled test-chambers are used containing one or several valves.
Static and Dynamic Stresses: The magnitude and distribution of stresses generated in the valve components during valve closure are essential design considerations which significantly effect the performance and durability of mechanical heart valve prostheses[16]. There are several basic types of stresses:
¨ Hertzian contact stress; which arises at the local contact area whenever 2 surfaces of the valve components press against each other either statically or dynamically.
¨ Dynamic transient stress; experienced by both the leaflet and housing, primarily in the form of flexural stress wave propogation
¨ Static stress; experienced by the valve components when the leaflet close completely and are loaded primarily by the hydrostatic pressure developed from the left ventricular chamber in the case of mitral valve or the aorta on the aortic valve.
These stresses were analyzed using an Edwards-Duromedics, mitral valve as example. It is concluded from this study that uniform contact between the leaflet and housing can reduce the static major stresses in the contact region up to 50% for the leaflet in comparison to the 3 point contact. When compared to the level of dynamic transient stresses, the effect of the static stresses on the durability of the valve is not as significant. It is also indicated that propagation of the flextural stress wave across the leaflet generates a high-frequency vibration of the leaflet. It is apparently related to the high frequency valve closing sound.
Patient Selection For Mechanical Valve Implantation
Fig4 suggests the way many cardiac surgeons select a mechanical or bioprosthetic valve. Mechanical valves have a decided advantage in children, young adults, and patients who have a high risk at reoparation. A lesser advantage is seen with small annulus sizes and in patients with atrial fibrillation who require anticoagulation. Bioprostheses gain some advantage in women who desire pregnancy and in patients older than 70 years. Finally, tissue valves have a definite advantage when there is a high risk of thromboembolism or an inability to anticoagulate the patient.
Just what will cause cardiac surgeons to select mechanical valves or bioprostheses in the future is difficult to determine. However, newer mechanical-valve must be directed at making them truly durable for all age groups.
MECHANICAL VALVE ADVANTAGE
Children
Patients< 40 years
High reoparation risk
Small Annular Size
Atrial fibrillation
Pregnancy desired
Patients> 70 years
High thromboembolism risk
High hemorrhage risk
TISSUE VALVE ADVANTAGE
References
1. http://www.chee.iit.edu/+3/banat.jpg
2. http://www./iii.com/shawn/heart.html
3. Aquilino Hurle, J Francisco Nistal, Jose M Revuelta Poor clinical performance of the Wessex porcine heart valve bioprosthesis at nine years’ follow-up Heart, 77: 319-324, 1997 (10).
4. Hirayama T, Roberts D, Mechanical trauma to red blood cells caused by Bjork-Shiley and Carpentier Edwards heart valves. Scand J. Thorac Cardiovasc Surg 19: 253-6, 19: 253-6, 1985
5. Biomaterials Science, An introduction to materials in science Buddy.D. Ratner, Allan S.Hoffman, Frederick J. Schoen, Jack E. Lemons San Diego, California, 1996
6. Cary W. Akins, MD Mechanical Cardiac Valvular Prostheses Ann Thorac Surg 52: 161-72, 1991
7. Polymeric Biomaterials Severian Dumitriu Polytechnic Ins. Jassy, Jassy 1994
8. Justify R. Bessel, Georgina Gower, David R. Craddock, John Stubberfield and Guy J. Maddern Thirty years experience with heart valve surgery: Isolated aortic valve replacement Aust. N.Z. J. Surg 66:799-805 ,1996
9. T. Chandy, G.S. Das, R.F. wilson, G.H.R. Rao Surface-immobilized biomolecules on albumin modified porcine pericardium for preventing thrombosis and calcification Artificial Heart and Cardiac Assist Devices The Int. J. Art. Org 22:8, pp. 547-558, 1999
10. Pauline B. van Wachem, Linda A. Brouwer, Raymond Zeeman, Piet J. Dijkstra In vivo behavior of Epoxy-Crosslinked porcine heart valve cusps walls J Biomed Res (Appl Biomater) 53: 18-27, 2000
11. Douglas A. Murphy, M:D:, Frederick H. Levine, M.D., Mortimer J. Buckley, M.D. Mechanical valves: A comparative analysis of the Starr-Edwards and Bjork-Shiley prostheses J Thorac Cardiovasc Surg 86: 746-752, 1983
12. Heiliger R. Lanbertz H. Geks J. Mittermayer C. Hydrodynamic investigation of mechanical bileaflet valves Artif Organs 12: 431-43 1988
13. G.M. Oantolos M.K/ Sharp influence and pressure on prosthetic valve regurgitation Int J. of Art. Organs 16: 3 pp. 151-154
14. Shoei- Shen Wang, Shu-Hsun chu Clinical use of Carbomedics and St. Jude Medical vaves Artificial organs 20: 12 1299-1303, 1996
15. M.O. Wendt, M. Pohl In vitro hemolysis by mechanical heart valve prostheses with tilting disc Int. J. of Artif Organs 15: 11 pp. 681-685, 1992
16. T.H.Chiang, H.Lam Static and dynamic stresses during valve closure of a bileaflet mechanical heart valve prostheses Int. J. of Artif. Organs 14: 12 pp. 781-788, 1991
16. G.Dubini, R. Pietrabissa Computational fluid dynamics of artificial heart valves Int. Artif. Organs 14: 338-42, 1991
