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'{{multiple issues| {{COI|date=March 2015}} {{Refimprove|date=November 2008}} {{More footnotes|article|date=November 2011}} {{Original research|date=November 2013}} }} An '''artificial lung valve''' is a device [[Implant (medicine)|implanted]] in the [[heart]] of a [[patient]] with [[valvular heart disease]].<ref>{{cite journal |doi=10.1038/nmat3627 |title=Nano-analytical electron microscopy reveals fundamental insights into human cardiovascular tissue calcification |year=2013 |last1=Bertazzo |first1=Sergio |last2=Gentleman |first2=Eileen |last3=Cloyd |first3=Kristy L. |last4=Chester |first4=Adrian H. |last5=Yacoub |first5=Magdi H. |last6=Stevens |first6=Molly M. |journal=Nature Materials |volume=12 |issue=6 |pages=576–83 |pmid=23603848}}</ref><ref>{{cite journal |doi=10.1038/nmat3663 |title=Cardiovascular calcification: Orbicular origins |year=2013 |last1=Miller |first1=Jordan D. |journal=Nature Materials |volume=12 |issue=6 |pages=476–8 |pmid=23695741}}</ref> When one of the four [[heart valve]]s malfunctions, the medical choice may be to replace the natural valve with an artificial valve. This requires [[Cardiac surgery|open-heart surgery]]. [[penile artery |Valves]] are integral to the normal [[Human physiology|physiological]] functioning of the [[human]] [[heart]]. Natural [[heart valve]]s are [[evolved]] to forms that perform the functional requirement of inducing unidirectional blood [[blood flow|flow]] through the valve structure from one chamber of the heart to another. Natural heart valves become [[dysfunctional]] for a variety of [[pathological]] causes. Some pathologies may require complete [[surgical]] replacement of the natural heart valve with a heart valve [[prosthesis]].<ref>{{cite journal |doi=10.1161/CIRCULATIONAHA.108.778886 |title=Prosthetic Heart Valves: Selection of the Optimal Prosthesis and Long-Term Management |year=2009 |last1=Pibarot |first1=P. |last2=Dumesnil |first2=J. G. |journal=Circulation |volume=119 |issue=7 |pages=1034–48 |pmid=19237674}}</ref> ==Types of heart valve prostheses== [[File:Mechanical heart valves.jpg|thumb|Different types of artificial heart valves<ref>{{cite journal|last1=Kostrzewa|first1=B|last2=Rybak|first2=Z|title=[History, present and future of biomaterials used for artificial heart valves].|journal=Polimery w medycynie|date=2013|volume=43|issue=3|pages=183–9|pmid=24377185}}<!--|accessdate=8 March 2015--></ref>]] There are three main types of artificial heart valves: the ''mechanical,''the ''biological,'' and the ''tissue engineered'' valves. * Mechanical heart valve ** [[Percutaneous]] implantation *** [[Stent]] framed *** Not framed ** [[Sternotomy]]/[[Thoracotomy]] implantation *** Ball and cage *** Tilting disk *** Bi-leaflet *** Tri-leaflet * Tissue (biological) heart valves ** [[Allograft]]/[[isograft]] ** [[Xenograft]] * Tissue-Engineered heart valves ==Mechanical valves== '''Mechanical heart valves''' (MHV) are prosthetics designed to replicate the function of the natural valves of the human heart. The human heart contains four valves: [[tricuspid valve]], [[pulmonic valve]], [[mitral valve]] and [[aortic valve]]. Their main purpose is to maintain unimpeded forward flow through the heart and from the heart into the major blood vessels connected to the heart, the [[pulmonary artery]] and the [[aorta]]. As a result of a number of disease processes, both acquired and congenital, any one of the four heart valves may malfunction and result in either stenosis (impeded forward flow) and/or backward flow (regurgitation). Either process burdens the heart and may lead to serious problems including [[heart failure]]. A mechanical heart valve is intended to replace a diseased heart valve with its prosthetic equivalent. There are two basic types of valves that can be used for valve replacement, [[wikt:mechanical|mechanical]] and tissue valves. Modern mechanical valves can last indefinitely (the equivalent of over 50,000 years in an accelerated valve wear tester).{{Citation needed|date=October 2013}} However, current mechanical heart valves all require lifelong treatment with anticoagulants (blood thinners), e.g. [[warfarin]], which requires monthly blood tests to monitor.{{Citation needed|date=October 2013}} This process of thinning the blood is called [[anticoagulation]]. Tissue heart valves, in contrast, do not require the use of anticoagulant drugs due to the improved blood flow dynamics resulting in less red cell damage and hence less clot formation.{{Citation needed|date=October 2013}} Their main weakness however, is their limited lifespan. Traditional tissue valves, made of [[pig]] heart valves, will last on average 15 years{{Citation needed|date=October 2013}} before they require replacement (but typically less in younger patients). ===Types of mechanical heart valves=== [[Image:Prosthetic Cardiac Ball Valves.jpg|thumb|1.&nbsp;Starr-Edwards Valve<br>2.&nbsp;Starr-Edwards Valve<br>3.&nbsp;Smeloff-Cutter Valve]] There are three major types of mechanical valves – ''caged-ball'', ''tilting-disk'' and ''bileaflet valve '' – with many modifications on these designs. [[Image:Starr-Edwards-Mitral-Valve.jpg|thumb|120px|left|Caged ball valve]] The first artificial heart valve was the '''caged-ball''', which utilizes a metal cage to house a silicone elastomer ball. When blood pressure in the chamber of the heart exceeds that of the pressure on the outside of the chamber the ball is pushed against the cage and allows blood to flow. At the completion of the heart's contraction, the pressure inside the chamber drops and is lower than beyond the valve, so the ball moves back against the base of the valve forming a seal. In 1952, [[Charles A. Hufnagel]] implanted caged-ball heart valves in ten patients (six survived the operation), marking the first long-term success in prosthetic heart valves.{{Citation needed|date=October 2013}} A similar valve was invented by Miles "Lowell" Edwards and [[Albert Starr]] in 1960 (commonly referred to as the Starr-Edwards Silastic Ball Valve).{{Citation needed|date=October 2013}} The first human implant was on Sept 21, 1960.{{Citation needed|date=October 2013}} It consisted of a silicone ball enclosed in a cage formed by wires originating from the valve housing. Caged ball valves have a high tendency to form blood clots, so the patient must have a high degree of anti-coagulation, usually with a target [[Prothrombin time#International normalized ratio|INR]] of 2.5-3.5.{{Citation needed|date=October 2013}} [[Edwards Lifesciences]] discontinued production of the Starr-Edwards valve in 2007.{{Citation needed|date=October 2013}} [[File:Chitra Valve.jpg|thumb|120px|left|tilting-disc valve]] Soon after came '''tilting-disc''' valves. The first clinically available tilting disk valve was the [[Bjork-Shiley valve]] and has undergone several significant design changes since its introduction in 1969.{{Citation needed|date=October 2013}} Tilting disk valves have a single circular occluder controlled by a metal strut. They are made of a metal ring covered by an [[ePTFE]] fabric, into which the [[surgical suture|suture]] threads are stitched in order to hold the valve in place. The metal ring holds, by means of two metal supports, a disc which opens and closes as the heart pumps blood through the valve. The disc is usually made of an extremely hard carbon material ([[pyrolytic carbon]]), in order to allow the valve to function for years without wearing out. The [[Medtronic]]-Hall model is the most common tilting-disc design in the US. In some models of mechanical valves, the disc is divided into two parts, which open and close as a door. [[File:Aortic Karboniks-1 bileafter prosthetic heart valve.jpg|thumb|120px|left|Bileaflet valve]] [[Bileaflet valve|'''Bileaflet''' heart valves]] consist of two semicircular leaflets that rotate about struts attached to the valve housing. This design was introduced in 1979{{Citation needed|date=October 2013}} and while they take care of some of the issues that were seen in the other models, bileaflets are vulnerable to backflow and so they cannot be considered as ideal. Bileaflet valves do, however, provide much more natural blood flow than caged-ball or tilting-disc implants. One of the main advantages of these valves is that they are well tolerated by the body. Only a small amount of blood thinner is needed to be taken by the patient each day in order to prevent clotting of the blood when flowing through the valve. These ''bileaflet'' valves have the advantage that they have a greater effective opening area (2.4–3.2 square cm c.f. 1.5–2.1 for the single-leaflet valves).{{Citation needed|date=October 2013}} Also, they are the least thrombogenic of the artificial valves. Mechanical heart valves are today very reliable and allow the patient to live a normal life. Most mechanical valves last for at least 20 to 30 years.{{Citation needed|date=October 2013}} ===Durability=== Mechanical heart valves have been traditionally considered to be more durable in comparison to their [[bioprosthetic]] counterparts. The struts and occluders are made out of either [[pyrolytic carbon]] or titanium coated with pyrolytic carbon,{{Citation needed|date=October 2013}} and the sewing ring cuff is [[Teflon]] (PTFE), polyester or dacron.{{Citation needed|date=October 2013}} The major load arises from transvalvular pressure generated at and after valve closure, and in cases where structural failure does happen, it is usually as a result of occluder impact on the components. [[Impact (mechanics)|Impact]] wear and [[friction]] wear dictate the loss of material in MHV. Impact wear usually occurs in the hinge regions of bileaflets, between the occluder and ring in tilting-discs, and between the ball and cage in caged-ball valves. Friction wear occurs between the occluder and strut in tilting-discs, and between the leaflet pivots and hinge cavities in bileaflets.{{Citation needed|date=October 2013}} MHV{{Define}}, made out of metal are also susceptible to fatigue failure owing to the [[polycrystalline]] characteristic of metals, but this is not an issue with pyrolytic carbon MHV because this material is not crystalline in nature.{{Citation needed|date=October 2013}} ===Cavitation=== [[Cavitation]] is an event that can lead to MHV failure. While this has been a relatively rare occurrence, in 1988 the Edwards-Duramedics bileaflet had 46 reported failures in 20,000 implants related to cavitation damage.{{Citation needed|date=October 2013}} Since then, manufacturers have made cavitation testing an essential part of the design verification process. Cavitation is the rapid formation of vaporous microbubbles in the fluid due to a local drop of pressure below the vaporization pressure at a given temperature. When conditions for cavitation are present bubbles will form and at the time of pressure recovery they will collapse or implode. This event will cause pressure or thermal shockwaves and fluid microjets which can damage a surface. These thermodynamic conditions are known to be the cause of MHV related erosion.{{Citation needed|date=October 2013}} The valvular event that causes such cavitating conditions to exist is the closing mechanics of the MHV. Several causes of cavitation relating to valve closure have been identified. Squeeze flow is cavitation that is said to occur as the occluder approaches the housing during closure and fluid is squeezed between the occluder and the valve housing causing a low pressure formation. Water hammer is cavitation caused by the sudden stop of the valve occluder as it contacts the valve housing. This sudden retardation of the fluid retrograde inertia is said to put the fluid under tension causing cavitation. Squeeze flow is said to form a cloud of bubbles at the circumferential lip of the occluder whereas water hammer is said to be seen as transient bubbles at the occlude housing.{{Citation needed|date=October 2013}} For either event, cavitation occurs on the upstream side of valve. Clinically, cavitation is of primary concern in the mitral position. This position is especially harsh due to the sudden ventricular pressure rise which drives the valve closure against a low left atrial pressure which is said to be the worst case condition thus position for cavitation to occur. Cavitation is also suspected as a contributing factor in blood cell damage and increased risk of thromboembolic complications.{{Citation needed|date=October 2013}} The temporal rate of change of the left ventricular, measured as a slope of the ventricular pressure curve (dP/dt) is regarded as the best indicator for cavitation potential. Most MHV investigated generate cavitation only when the dP/dt is well above the physiological range. However investigations have found that several tilting disc valves and only one bileaflet valve, the Edwards-Duromedics, generate cavitation within the physiological range. Investigations have repeatedly demonstrated that bileaflet valves, with the exception of the Edwards Duramedics design, cavitate only at dP/dt levels well above the physiological range.{{Citation needed|date=October 2013}} ===Fluid mechanics=== Many of the complications associated with MHV can be explained through fluid mechanics. For example, thrombus formation is a debilitating side effect of high shear stresses created by the design of the valves. An ideal heart valve from an engineering perspective would produce minimal pressure drops, have small regurgitation volumes, minimize turbulence, reduce prevalence of high stresses, and not create flow separations in the vicinity of the valve.{{Citation needed|date=October 2013}} One measure of the quality of a valve is the effective orifice area (EOA), which can be calculated as follows: <math>EOA(\mathrm{cm}^2) = \frac{Q_{rms}}{51.6\sqrt{\Delta p}}\ </math> where <math>Q_{rms}</math> is the root mean square [[Systole (medicine)|systolic]]/[[diastolic]] flow rate (cm³/s) and <math>\Delta p</math> is the mean systolic/diastolic pressure drop ([[mmHg]]). This is a measure of how much the prosthesis impedes blood flow through the valve. A higher EOA corresponds to a smaller energy loss. The performance index (PI) normalizes the EOA by valve size and is a size-independent measure of the valve’s resistance characteristics. Bileaflet valves typically have higher PI’s than tilted-disc models, which in turn have higher PI’s than caged-ball models.{{Citation needed|date=October 2013}} As blood flows through a prosthetic heart valve, a sudden pressure drop occurs across the valve due to the reduction in cross-sectional area within the valve housing. This can be quantified through the continuity equation and Bernoulli’s equation: <math>A_1V_1 = A_2V_2</math> <math>P_1 + \frac{1}{2} \rho _1 V_1^2 = P_2 + \frac{1}{2} \rho_2 V_2^2</math> where ''A'' represents the cross-sectional area, ''P'' is [[pressure]], <math>\rho</math> is [[density]], and ''V'' is the [[velocity]].{{Citation needed|date=October 2013}} As cross-sectional area decreases in the valve, velocity increases and pressure drops as a result. This effect is more dramatic in caged-ball valves than in tilting-disc and bileaflet valves. A larger systolic pressure is required to drive flow forward in order to compensate for a large pressure drop, so it should be minimized.{{Citation needed|date=October 2013}} Regurgitation is the sum of retrograde flow during the closing motion of the valve and leakage flow after closure. It is directly proportional to valve size and is also dependent on valve type. Typically, caged-ball valves have a low amount of regurgitation as there is very little leakage. Tilting-disc and bileaflet valves are comparable, with the bileaflet valves have a slightly larger regurgitation volume. Bioprosthetics prevail over MHV in this case, as they have virtually no regurgitation volume.{{Citation needed|date=October 2013}} Turbulence and high shear stresses are also major issues with MHV, as they can fracture the valve housing or components, or induce blood damage. A large flow gradient can lead to these factors, so flow separation and stagnation should be as small as possible. High stresses are created at the edges of the annular jet in caged-ball valves, in narrow regions at the edges of the major orifice jet in tilting-disc valves, and in regions immediately distal to the valve leaflets in bileaflet valves. The implications of blood damage from these stresses are discussed in the next section.{{Citation needed|date=October 2013}} The cavitation phenomenon can also be described using fluid mechanics. This can result from pressure oscillations, flow deceleration, tip vortices, streamline contraction, and squeeze jets. This last cause is the most contributive factor to cavitation. The squeeze jets are formed when the valve is closing and the blood between the occluder and valve housing is “squeezed” out to create a high-speed jet. This in turn creates intense vortices with very low pressures that can lead to cavitation.{{Citation needed|date=October 2013}} ===Blood damage=== One of the major drawbacks of mechanical heart valves is that patients with these implants require consistent anti-coagulation therapy. Clots formed by red blood cell (RBC) and platelet damage can block up blood vessels and lead to very serious consequences. Clotting occurs in one of three basic pathways: tissue factor exposure, platelet activation, or contact activation by foreign materials, and in three steps: initiation, amplification, and propagation.{{Citation needed|date=October 2013}} In the tissue factor exposure path, initiation begins when cells are ruptured and expose tissue factor (TF). Plasma Factor (f) VII binds to TF and sets off a chain reaction which activates fXa and fVa which bind to each other to produce thrombin which in turn activates platelets and fVIII. The platelets activate by binding to the damaged tissue in the initiation phase, and fibrin stabilizes the clot during the propagation phase.{{Citation needed|date=October 2013}} The platelet activation pathway is triggered when stresses reach a level above 6 to 8 [[pascal (unit)|Pa]] (60–80 dyn/cm²). The steps involved with this are less clearly understood, but initiation begins with the binding of vWF from the plasma to GPIb on the platelet. This is followed by a large influx of Ca<sup>2+</sup> ions, which activates the platelets. GPIIb-IIIa facilitates platelet-platelet adhesion during amplification. The propagation step is still under study.{{Citation needed|date=October 2013}} Contact activation begins when fXII binds to a procoagulant surface. This in turn activates prekallikrein (PK) and high-molecular-weight kininogen (HK). Eventually, HKa-PK and HKa-fXI complexes form on the surface. In amplification, Hka-FXIa complexes activate fIX to fIXa, which in turn forms thrombin and platelets. Proteins buildup on the surface and facilitate platelet adhesion and tissue growth in the propagation stage.{{Citation needed|date=October 2013}} All MHV models are vulnerable to thrombus formation due to high shear stress, stagnation, and flow separation. The caged-ball designs experience high stresses at the walls that can damage cells, as well as flow separation due to high-velocity reverse flow surrounded by stagnant flow. Tilting-disc valves have flow separation behind the valve struts and disc as a result of a combination of high velocity and stagnant flows. The bileaflet models have high stresses during forward and leakage flows as well as adjacent stagnant flow in the hinge area. As it turns out, the hinge area is the most critical part of bileaflets and is where the thrombus formation usually prevails.{{Citation needed|date=October 2013}} In general, blood damage affects valves in both the mitral and aortic positions. High stresses during leakage flow in aortal valves result from higher transvalvular pressures, and high stresses occur during forward flow for mitral valves. Valvular thrombosis is most common in mitral prosthetics. The caged-ball model is better than the other two models in terms of controlling this problem, because it is at a lower risk for thrombosis and it is gradual when it does happen. The bileaflet is more adaptable to this problem than the tilting-disc model because if one leaflet stops working, the other can still function. However, if the hinge is blocked, both leaflets will stop functioning.{{Citation needed|date=October 2013}} Because all models experience high stresses, patients with mechanical heart valve implants require anti-coagulation therapy. Bioprosthetics are less prone to develop blood clotting, but the trade-off concerning durability generally favors their use in patients older than age 55.{{Citation needed|date=October 2013}} Mechanical heart valves can also cause [[mechanical hemolytic anemia]] with hemolysis of the [[red blood cell]]s as they pass through the valve.{{Citation needed|date=October 2013}} ==Tissue (biological) valves== ''Biological valves'' are valves of animals, like pigs, which undergo several chemical procedures in order to make them suitable for implantation in the human heart. The porcine (or pig) heart is most similar to the human heart, and therefore represents the best anatomical fit for replacement. Implantation of a porcine valve is a type of [[xenotransplantation]], also known as a xenograft, which means a transplant from one species (in this case a pig) to another. There are some risks associated with a xenograft such as the human body's tendency to reject foreign material. Medication can be used to retard this effect, but is not always successful.{{Citation needed|date=October 2013}} Another type of biological valve utilizes biological tissue to make leaflets that are sewn into a metal frame. This tissue is typically harvested from the ''Pericardial Sac'' of either cows or horses. The [[pericardial sac]] is particularly well suited for a valve leaflet due to its extremely durable physical properties. This type of biological valve is extremely effective means of valve replacement. The tissue is sterilized so that the biological markers are removed, eliminating a response from the host's immune system. The leaflets are flexible and durable and do not require the patient to take blood thinners for the rest of their life.{{Citation needed|date=October 2013}} The most used heart valves in the US, Britain and EU are those utilizing tissue leaflets. Mechanical valves are more commonly used in Asia and Latin America.{{Citation needed|date=October 2013}} The following companies manufacture tissue heart valves: Edwards Lifesciences, Medtronic, St. Jude Medical, Sorin, Medtronic ATS Medical, 3F Therapeutics, [[CryoLife]], and [[LifeNet Health]].{{Citation needed|date=October 2013}} Recently, researchers have begun working to grow heart valves in vitro. Autologous cells are seeded on a scaffold, typically made from a biodegradable polymer such as PGA or PLA. The scaffolding acts as an artificial extra-cellular matrix, guiding tissue growth into the correct 3D structure of the heart valve. Mechanical stimuli must be simulated in the culture in order to condition the tissue for physiological stress in vivo. These heart valves have not yet reached clinical trials.<ref>Neuenschwander, S., & P, H. S. (January 01, 2004). Heart valve tissue engineering. Transplant Immunology, 12, 359-365.</ref> ==Functional requirements of heart valve prostheses== The functioning of natural heart valves is characterized by many advantages: * Minimal [[Regurgitation (circulation)|regurgitation]] – This means that the amount of [[blood]] lost upstream as the valve closes is small. For example, closure regurgitation through the [[mitral valve]] would result in some blood loss from the left [[Ventricle (heart)|ventricle]] to the left [[Atrium (heart)|atrium]] as the mitral valve closes. Some degree of valvular regurgitation is inevitable and natural, up to around 5ml per beat.<ref>{{cite journal |pmid=22474745 |year=2012 |last1=Kasegawa |first1=H |last2=Iwasaki |first2=K |last3=Kusunose |first3=S |last4=Tatusta |first4=R |last5=Doi |first5=T |last6=Yasuda |first6=H |last7=Umezu |first7=M |title=Assessment of a novel stentless mitral valve using a pulsatile mitral valve simulator |volume=21 |issue=1 |pages=71–5 |journal=The Journal of heart valve disease}}</ref> However, several heart valve pathologies (e.g. rheumatic [[endocarditis]]) may lead to clinically significant valvular regurgitation. A desirable characteristic of heart valve prostheses is that regurgitation is minimal over the full range of [[physiological]] heart function (i.e. complete functional envelope of [[cardiac output]] vs. [[heart rate]]). * Minimal transvalvular pressure gradient – Whenever a [[fluid]] flows through a restriction, such as a valve, a [[pressure]] [[gradient]] arises over the restriction. This pressure gradient is a result of the increased resistance to flow through the restriction. Natural heart valves have a low transvalvular pressure gradient as they present little obstruction to the flow through themselves, normally less than 16 mmHg. A desirable characteristic of heart valve prostheses is that their transvalvular pressure gradient is as small as possible. * Non-[[thrombosis|thrombogenic]] – As natural heart valves are lined with an [[endothelium]] continuous with the endothelium lining the heart chambers they are not normally thrombogenic. This is important as should [[thrombus|thrombi]] form on the [[heart valve leaflets]] and become seeded with [[bacteria]], so called "[[bacterial vegetation]]s" will form. Such vegetations are difficult for the body to deal with as the normal [[physiology|physiological]] defense mechanisms are not present within the valve leaflets because they are [[Blood vessel|avascular]] and largely composed of [[connective tissue]] (Fixme: Create article discussing the pathgonesis of leaflet bacterial vegetations.). Should bacterial vegetations form on the valve leafets they may continually seed [[bacteria]] into the [[arterial tree]] which may lead to [[bacteremia]] or [[septicaemia]]. Portions of the vegetation may also break off forming [[Embolism|septic emboli]]. Septic emboli can lodge anywhere in the [[arterial tree]] (e.g. [[brain]], [[bowel]], [[lungs]]) causing local infectious [[Focus (geometry)|foci]]. Even dislodged fragments from uninfected thrombi can be hazardous as they can lodge in, and block, downstream [[artery|arteries]] (e.g. [[coronary artery|coronary arteries]] leading to [[myocardial infarction]], [[cerebral arteries]] leading to [[stroke]], see [[embolism]]). A desirable characteristic of heart valve prostheses is that they are non or minimally thrombogenic. * Self-repairing – Although of limited extent compared to well vascularised tissue (e.g. [[muscle]]), the valve leaflets do retain some capacity for repair due to the presence of regenerative [[cell (biology)|cells]] (e.g. [[fibroblasts]]) in the [[connective tissue]] from which the leaflets are composed. As the human heart beats approximately 3.4x10<sup>9</sup> times during a typical human lifespan this limited but nevertheless present repair capacity is critically important. No heart valve prostheses can currently self-repair but replacement tissues grown using [[stem cell]] technology may eventually offer such capabilities.{{Citation needed|date=October 2013}} * Rapid dynamic response – STD ==Design challenges of heart valve prostheses== [[Image:BiologicalValves.JPG|thumb|150px|A replaceable model of Cardiac Biological Valve Prosthesis.<ref name="dedalus">{{cite journal |last1=Lyra |first1=R. M. |last2=Leirner |first2=A. A. |last3=Pomerantzeff |first3=Pablo Maria Alberto |last4=Nyashida |first4=S. |last5=Jatene |first5=Adib |title=Estudo in vitro, de uma bioprotese recambiavel |trans-title=In vitro study of a recambiavel bioprosthesis |language=Portuguese |journal=Revista da Sociedade de Cardiologia do Estado de São Paulo |volume=2 |issue=2 Suppl B |pages=71 |year=1992}}</ref> <ref name="dedalus_a">{{cite journal |last1=Lyra |first1=R. M. |last2=Leirner |first2=A. A. |last3=Pomerantzeff |first3=Pablo Maria Alberto |last4=Hyashida |first4=S. |last5=Jatene |first5=Adib |title=Novo modelo de bioprotese recambiavel |trans-title=New model of recambiavel bioprosthesis |journal=Arquivos Brasileiros de Cardiologia |volume=59 |issue=Suppl 2 |pages=221 |year=1992}}</ref>]] * Thrombogenesis / haemocompatibility ** Mechanisms: *** Forward and backward flow shear *** Static leakage shear *** Presence of foreign material (i.e. intrinsic coagulation cascade) *** Cellular maceration * Valve-tissue interaction * Wear * Blockage * Getting stuck * Dynamic responsiveness * Failure safety * Valve orifice to anatomical orifice ratio * Trans-valvular pressure gradient * Minimal leakages * Detachable And Replaceable Models Of Heart Valve Prostheses ==Replaceable models of heart valve prostheses== Mechanical or biological (bioprostheses or "tissue valves"), '''the replaceable models of implantable heart valve prostheses''' are made by two or three mechanical components. The gear attachment mechanism usually uses the coil effect or the bayonet coupling system.{{Citation needed|date=October 2013}} '''The replaceable models of implantable heart valve prostheses''' are typically supplied with a sewing or suturing ring surrounding the valve body or stent that is to be sutured by the surgeon to the valvar rim.{{Citation needed|date=October 2013}} The biggest challenge in this type of prostheses is the difficulty in its future removal. This is due to the formation of pannus fibrotic around the valve body and sewing ring. To separate the parts is very laborious, keeping intact the sewing ring, which will be used in the coupling of the new valve. To easily remove the old replaceable bioprostheses, its "stent" can be sectioned to dismount its framework and so facilitate its removal from the sewing ring.{{Citation needed|date=October 2013}} <gallery> File:The replaceable model of implantable heart valve bioprosthese de Menezes Lyra R 1992.tif </gallery> Time line of the detachable and replaceable models of heart valve prostheses: * 1984 Martin, J. R <ref>{{cite journal |last1=Martin |first1=J. R |last2=Grassi |first2=E. D |last3=Barone |first3=A |last4=Milei |first4=J |last5=Barone |first5=H. D. |title=Protesis valvular cardiaca desmontable. Implante experimental 'in vivo' y resustitucion valvular alejada |trans-title=Dismountable heart valve prosthesis. In vivo experimental implant and delayed valvular replacement |language=Portuguese |journal=Revista Argentina de Cirugía |volume=46 |issue=6 |pages=275–6 |year=1984}}</ref> * 1984 Martin, J. R <ref>{{cite journal |last1=Martin |first1=J. R |last2=Barone |first2=H. D |last3=Barone |first3=A |last4=Milei |first4=J |last5=Grassi |first5=E. D. |title=Anel portador de valvulas cardiacas |trans-title=Ring porter of cardiac valves |language=Portuguese |journal=Arquivos brasileiros de cardiologia |volume=43 |issue=6 |pages=415–21 |year=1984 |pmid=6399678 |url=http://www.arquivosonline.com.br/pesquisartigos/Pdfs/1984/v43n6/43060007.pdf}}</ref> * 1984 Martin, J. R <ref>{{cite journal |last1=Martin |first1=J. R |last2=Grassi |first2=E. D |last3=Barone |first3=A |last4=Barone |first4=H. D |last5=Patane |first5=A. M. |title=Protesis valvular cardiaca demontable Desarrollo experimental (Prototipo I) |trans-title=Dismountable heart valve prosthesis.Experimental development (Prototype I) |language=Portuguese |journal=Revista Argentina de Cirugía |volume=46 |issue=6 |pages=272–4 |year=1984}}</ref> * 1987 Fernandez J <ref>{{cite journal |pmid=15227327 |year=1987 |last1=Fernandez |first1=J |last2=Gonzalez-Lavin |first2=L |last3=Maranhao |first3=V |last4=Yang |first4=SS |title=A new bioprosthesis for aortic and mitral valve replacement: Preliminary evaluation of the Tascon valve |volume=14 |issue=1 |pages=31–8 |pmc=324690 |journal=Texas Heart Institute journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital}}</ref> * 1988 Cooper DK <ref>{{cite journal |doi=10.1016/S0003-4975(10)64532-8 |title=Initial Experimental Experience with a 'Replaceable' Cardiac Valve Prosthesis |year=1988 |last1=Cooper |first1=D.K.C. |last2=Wicomb |first2=W.N. |last3=Gould |first3=Gwyneth M. |last4=Boonzaier |first4=D. |journal=The Annals of Thoracic Surgery |volume=45 |issue=5 |pages=554–8 |pmid=3365047}}</ref> * 1992 Lyra, R M <ref name="dedalus" /> * 1992 Lyra, R M <ref name="dedalus_a" /> * 1992 Jansen J <ref>{{cite journal |doi=10.1111/j.1525-1594.1992.tb00313.x |title=Detachable Shape-Memory Sewing Ring for Heart Valves |year=2008 |last1=Jansen |first1=Josef |last2=Willeke |first2=Sebastian |last3=Reul |first3=Helmul |last4=Rau |first4=Günter |journal=Artificial Organs |volume=16 |issue=3 |pages=294–7 |pmid=10078262}}</ref> ==Typical configuration of a heart valve prosthesis== * Anchor * Leaflets ==History== [[File:Hufnagel heart Valve15111214-photos 309.jpg|thumb|upright|Hufnagel heart Valve]] In the 1950s, Dr. [[Charles A. Hufnagel]] developed an artificial heart valve. His mechanical valve consisted of two parts, a ball that is surrounded by a cage which is the first variation of the ball-in-cage valves. Originally, the cage and the ball were constructed using [[Plexiglas]]. Due to the noise created by the contacts between the moving ball and the cage, the ball was later changed to use [[silicone]]-coated material. The first implantation of mechanical heart valve to human was performed by Dr. Hufnagel on September 11, 1952, using the valve that he developed. This event accelerated the development of other artificial heart valves.<ref>{{cite journal|last1=Butany|first1=J|last2=Ahluwalia|first2=MS|last3=Fayet|first3=C|last4=Munroe|first4=C|last5=Blit|first5=P|last6=Ahn|first6=C|title=Hufnagel valve: the first prosthetic mechanical valve.|journal=Cardiovascular Pathology|date=2002|volume=11|issue=6|pages=351–3|pmid=12459437|doi=10.1016/s1054-8807(02)00132-1}}<!--|accessdate=8 March 2015--></ref> ==Additional images== <gallery> File:Blausen 0056 ArtificialHeartValve.png|3D Rendering of Mechanical Valve File:Blausen 0057 ArtificialHeartValve StFrancis.png|3D Rendering of Mechanical Valve (St. Francis model) </gallery> ==See also== * [[Artificial heart]] == References == {{Reflist}} == Further reading == * {{cite journal |pmid=7392405 |year=1980 |last1=Bendet |first1=IaA |title=Psychological aspects of the rehabilitation of patients after the surgical treatment of heart defects |last2=Morozov |first2=SM |last3=[[:fr:Victor Skumin|Skumin]]|first3=VA |script-title=ru:Психологические аспекты реабилитации больных после хирургического лечения пороков сердца |trans-title=Psychological aspects of the rehabilitation of patients after the surgical treatment of heart defects |language=Russian |volume=20 |issue=6 |pages=45–51 |journal=Kardiologiia}} * {{cite journal |pmid=259874 |year=1979 |last1=[[:fr:Victor Skumin|Skumin]] |first1=VA |title=Nurse's role in medico-psychological rehabilitation of patients with artificial heart valves |volume=38 |issue=9 |pages=44–5 |journal=Meditsinskaia Sestra}} * {{cite journal |pmid=6758444 |year=1982 |last1=[[:fr:Victor Skumin|Skumin]]|first1=VA |title=Nonpsychotic mental disorders in patients with acquired heart defects before and after surgery (review) |volume=82 |issue=11 |pages=130–5 |journal=Zhurnal nevropatologii i psikhiatrii imeni S.S. Korsakova}} *{{cite journal |pmid=2911200 |year=1989 |last1=Klepetko |first1=W |last2=Moritz |first2=A |last3=Mlczoch |first3=J |last4=Schurawitzki |first4=H |last5=Domanig |first5=E |last6=Wolner |first6=E |title=Leaflet fracture in Edwards-Duromedics bileaflet valves |volume=97 |issue=1 |pages=90–4 |journal=The Journal of Thoracic and Cardiovascular Surgery}} *{{cite journal |pmid=9605082 |year=1998 |last1=Podesser |first1=BK |last2=Khuenl-Brady |first2=G |last3=Eigenbauer |first3=E |last4=Roedler |first4=S |last5=Schmiedberger |first5=A |last6=Wolner |first6=E |last7=Moritz |first7=A |title=Long-term results of heart valve replacement with the Edwards Duromedics bileaflet prosthesis: A prospective ten-year clinical follow-up |volume=115 |issue=5 |pages=1121–9 |journal=The Journal of Thoracic and Cardiovascular Surgery |doi=10.1016/s0022-5223(98)70412-x}} * Knapp RJ, Daily JW, Hammitt FG. 1970. Cavitation. New York: McGraw-Hill Int. Book Co. *{{cite journal |pmid=12893035 |year=2003 |last1=Lim |first1=WL |last2=Chew |first2=YT |last3=Low |first3=HT |last4=Foo |first4=WL |title=Cavitation phenomena in mechanical heart valves: The role of squeeze flow velocity and contact area on cavitation initiation between two impinging rods |volume=36 |issue=9 |pages=1269–80 |journal=Journal of Biomechanics |doi=10.1016/s0021-9290(03)00161-1}} *{{cite journal |pmid=7798287 |year=1994 |last1=Bluestein |first1=D |last2=Einav |first2=S |last3=Hwang |first3=NH |title=A squeeze flow phenomenon at the closing of a bileaflet mechanical heart valve prosthesis |volume=27 |issue=11 |pages=1369–78 |journal=Journal of Biomechanics |doi=10.1016/0021-9290(94)90046-9}} *{{cite journal |pmid=2045192 |year=1991 |last1=Graf |first1=T |last2=Fischer |first2=H |last3=Reul |first3=H |last4=Rau |first4=G |title=Cavitation potential of mechanical heart valve prostheses |volume=14 |issue=3 |pages=169–74 |journal=The International journal of Artificial Organs}} *{{cite book |last1=Kafesjian |first1=R |last2=Wieting |first2=DW |last3=Ely |first3=J |last4=Chahine |first4=GL |last5=Frederick |first5=GS |last6=Watson |first6=RE |year=1990 |chapter=Characterization of Cavitation Potential of Pyrolitic Carbon |pages=509–16 |editor1-first=Endré |editor1-last=Bodnar |title=Surgery for Heart Valve Disease: Proceedings of the 1989 Symposium |publisher=ICR |isbn=978-1-872743-00-4}} *{{cite journal |pmid=8665016 |year=1996 |last1=Chahine |first1=GL |title=Scaling of mechanical heart valves for cavitation inception: Observation and acoustic detection |volume=5 |issue=2 |pages=207–14; discussion 214–5 |journal=The Journal of Heart Valve Disease}} *{{cite journal |pmid=8944940 |year=1996 |last1=Zapanta |first1=CM |last2=Stinebring |first2=DR |last3=Sneckenberger |first3=DS |last4=Deutsch |first4=S |last5=Geselowitz |first5=DB |last6=Tarbell |first6=JM |last7=Synder |first7=AJ |last8=Rosenberg |first8=G |last9=Weiss |first9=WJ |last10=Pae |first10=WE |last11=Pierce |first11=WS |title=In vivo observation of cavitation on prosthetic heart valves |volume=42 |issue=5 |pages=M550–5 |journal=ASAIO Journal |doi=10.1097/00002480-199609000-00047}} *{{cite journal |pmid=8061875 |year=1994 |last1=Richard |first1=G |last2=Beavan |first2=A |last3=Strzepa |first3=P |title=Cavitation threshold ranking and erosion characteristics of bileaflet heart valve prostheses |volume=3 Suppl 1 |pages=S94–101 |journal=The Journal of Heart Valve Disease}} ==External links== *[https://web.archive.org/web/20061113095223/http://www.mayoclinic.org/heart-valve-surgery/treatment.html Page describing types of heart valve replacements] *{{cite web |url=http://www.sciencedaily.com/releases/2011/11/111122113212.htm |title=New Design for Mechanical Heart Valves |date=November 23, 2011 |publisher=ScienceDaily}} {{Medicine}} [[Category:Cardiology]] [[Category:Cardiac surgery]] [[Category:Implants (medicine)]] [[Category:Prosthetics]]'
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'{{multiple issues| {{COI|date=March 2015}} {{Refimprove|date=November 2008}} {{More footnotes|article|date=November 2011}} {{Original research|date=November 2013}} }} An '''artificial lung valve''' is a device [[Implant (medicine)|implanted]] in the [[heart]] of a [[patient]] with [[valvular heart disease]].<ref>{{cite journal |doi=10.1038/nmat3627 |title=Nano-analytical electron microscopy reveals fundamental insights into human cardiovascular tissue calcification |year=2013 |last1=Bertazzo |first1=Sergio |last2=Gentleman |first2=Eileen |last3=Cloyd |first3=Kristy L. |last4=Chester |first4=Adrian H. |last5=Yacoub |first5=Magdi H. |last6=Stevens |first6=Molly M. |journal=Nature Materials |volume=12 |issue=6 |pages=576–83 |pmid=23603848}}</ref><ref>{{cite journal |doi=10.1038/nmat3663 |title=Cardiovascular calcification: Orbicular origins |year=2013 |last1=Miller |first1=Jordan D. |journal=Nature Materials |volume=12 |issue=6 |pages=476–8 |pmid=23695741}}</ref> When one of the four [[heart valve]]s malfunctions, the medical choice may be to replace the natural valve with an artificial valve. This requires [[Cardiac surgery|open-heart surgery]]. [[penile artery |Penis]] are integral to the normal [[Human physiology|physiological]] functioning of the [[human]] [[heart]]. Natural [[heart valve]]s are [[evolved]] to forms that perform the functional requirement of inducing unidirectional blood [[blood flow|flow]] through the valve structure from one chamber of the heart to another. Natural heart valves become [[dysfunctional]] for a variety of [[pathological]] causes. Some pathologies may require complete [[surgical]] replacement of the natural heart valve with a heart valve [[prosthesis]].<ref>{{cite journal |doi=10.1161/CIRCULATIONAHA.108.778886 |title=Prosthetic Heart Valves: Selection of the Optimal Prosthesis and Long-Term Management |year=2009 |last1=Pibarot |first1=P. |last2=Dumesnil |first2=J. G. |journal=Circulation |volume=119 |issue=7 |pages=1034–48 |pmid=19237674}}</ref> ==Types of heart valve prostheses== [[File:Mechanical heart valves.jpg|thumb|Different types of artificial heart valves<ref>{{cite journal|last1=Kostrzewa|first1=B|last2=Rybak|first2=Z|title=[History, present and future of biomaterials used for artificial heart valves].|journal=Polimery w medycynie|date=2013|volume=43|issue=3|pages=183–9|pmid=24377185}}<!--|accessdate=8 March 2015--></ref>]] There are three main types of artificial heart valves: the ''mechanical,''the ''biological,'' and the ''tissue engineered'' valves. * Mechanical heart valve ** [[Percutaneous]] implantation *** [[Stent]] framed *** Not framed ** [[Sternotomy]]/[[Thoracotomy]] implantation *** Ball and cage *** Tilting disk *** Bi-leaflet *** Tri-leaflet * Tissue (biological) heart valves ** [[Allograft]]/[[isograft]] ** [[Xenograft]] * Tissue-Engineered heart valves ==Mechanical valves== '''Mechanical heart valves''' (MHV) are prosthetics designed to replicate the function of the natural valves of the human heart. The human heart contains four valves: [[tricuspid valve]], [[pulmonic valve]], [[mitral valve]] and [[aortic valve]]. Their main purpose is to maintain unimpeded forward flow through the heart and from the heart into the major blood vessels connected to the heart, the [[pulmonary artery]] and the [[aorta]]. As a result of a number of disease processes, both acquired and congenital, any one of the four heart valves may malfunction and result in either stenosis (impeded forward flow) and/or backward flow (regurgitation). Either process burdens the heart and may lead to serious problems including [[heart failure]]. A mechanical heart valve is intended to replace a diseased heart valve with its prosthetic equivalent. There are two basic types of valves that can be used for valve replacement, [[wikt:mechanical|mechanical]] and tissue valves. Modern mechanical valves can last indefinitely (the equivalent of over 50,000 years in an accelerated valve wear tester).{{Citation needed|date=October 2013}} However, current mechanical heart valves all require lifelong treatment with anticoagulants (blood thinners), e.g. [[warfarin]], which requires monthly blood tests to monitor.{{Citation needed|date=October 2013}} This process of thinning the blood is called [[anticoagulation]]. Tissue heart valves, in contrast, do not require the use of anticoagulant drugs due to the improved blood flow dynamics resulting in less red cell damage and hence less clot formation.{{Citation needed|date=October 2013}} Their main weakness however, is their limited lifespan. Traditional tissue valves, made of [[pig]] heart valves, will last on average 15 years{{Citation needed|date=October 2013}} before they require replacement (but typically less in younger patients). ===Types of mechanical heart valves=== [[Image:Prosthetic Cardiac Ball Valves.jpg|thumb|1.&nbsp;Starr-Edwards Valve<br>2.&nbsp;Starr-Edwards Valve<br>3.&nbsp;Smeloff-Cutter Valve]] There are three major types of mechanical valves – ''caged-ball'', ''tilting-disk'' and ''bileaflet valve '' – with many modifications on these designs. [[Image:Starr-Edwards-Mitral-Valve.jpg|thumb|120px|left|Caged ball valve]] The first artificial heart valve was the '''caged-ball''', which utilizes a metal cage to house a silicone elastomer ball. When blood pressure in the chamber of the heart exceeds that of the pressure on the outside of the chamber the ball is pushed against the cage and allows blood to flow. At the completion of the heart's contraction, the pressure inside the chamber drops and is lower than beyond the valve, so the ball moves back against the base of the valve forming a seal. In 1952, [[Charles A. Hufnagel]] implanted caged-ball heart valves in ten patients (six survived the operation), marking the first long-term success in prosthetic heart valves.{{Citation needed|date=October 2013}} A similar valve was invented by Miles "Lowell" Edwards and [[Albert Starr]] in 1960 (commonly referred to as the Starr-Edwards Silastic Ball Valve).{{Citation needed|date=October 2013}} The first human implant was on Sept 21, 1960.{{Citation needed|date=October 2013}} It consisted of a silicone ball enclosed in a cage formed by wires originating from the valve housing. Caged ball valves have a high tendency to form blood clots, so the patient must have a high degree of anti-coagulation, usually with a target [[Prothrombin time#International normalized ratio|INR]] of 2.5-3.5.{{Citation needed|date=October 2013}} [[Edwards Lifesciences]] discontinued production of the Starr-Edwards valve in 2007.{{Citation needed|date=October 2013}} [[File:Chitra Valve.jpg|thumb|120px|left|tilting-disc valve]] Soon after came '''tilting-disc''' valves. The first clinically available tilting disk valve was the [[Bjork-Shiley valve]] and has undergone several significant design changes since its introduction in 1969.{{Citation needed|date=October 2013}} Tilting disk valves have a single circular occluder controlled by a metal strut. They are made of a metal ring covered by an [[ePTFE]] fabric, into which the [[surgical suture|suture]] threads are stitched in order to hold the valve in place. The metal ring holds, by means of two metal supports, a disc which opens and closes as the heart pumps blood through the valve. The disc is usually made of an extremely hard carbon material ([[pyrolytic carbon]]), in order to allow the valve to function for years without wearing out. The [[Medtronic]]-Hall model is the most common tilting-disc design in the US. In some models of mechanical valves, the disc is divided into two parts, which open and close as a door. [[File:Aortic Karboniks-1 bileafter prosthetic heart valve.jpg|thumb|120px|left|Bileaflet valve]] [[Bileaflet valve|'''Bileaflet''' heart valves]] consist of two semicircular leaflets that rotate about struts attached to the valve housing. This design was introduced in 1979{{Citation needed|date=October 2013}} and while they take care of some of the issues that were seen in the other models, bileaflets are vulnerable to backflow and so they cannot be considered as ideal. Bileaflet valves do, however, provide much more natural blood flow than caged-ball or tilting-disc implants. One of the main advantages of these valves is that they are well tolerated by the body. Only a small amount of blood thinner is needed to be taken by the patient each day in order to prevent clotting of the blood when flowing through the valve. These ''bileaflet'' valves have the advantage that they have a greater effective opening area (2.4–3.2 square cm c.f. 1.5–2.1 for the single-leaflet valves).{{Citation needed|date=October 2013}} Also, they are the least thrombogenic of the artificial valves. Mechanical heart valves are today very reliable and allow the patient to live a normal life. Most mechanical valves last for at least 20 to 30 years.{{Citation needed|date=October 2013}} ===Durability=== Mechanical heart valves have been traditionally considered to be more durable in comparison to their [[bioprosthetic]] counterparts. The struts and occluders are made out of either [[pyrolytic carbon]] or titanium coated with pyrolytic carbon,{{Citation needed|date=October 2013}} and the sewing ring cuff is [[Teflon]] (PTFE), polyester or dacron.{{Citation needed|date=October 2013}} The major load arises from transvalvular pressure generated at and after valve closure, and in cases where structural failure does happen, it is usually as a result of occluder impact on the components. [[Impact (mechanics)|Impact]] wear and [[friction]] wear dictate the loss of material in MHV. Impact wear usually occurs in the hinge regions of bileaflets, between the occluder and ring in tilting-discs, and between the ball and cage in caged-ball valves. Friction wear occurs between the occluder and strut in tilting-discs, and between the leaflet pivots and hinge cavities in bileaflets.{{Citation needed|date=October 2013}} MHV{{Define}}, made out of metal are also susceptible to fatigue failure owing to the [[polycrystalline]] characteristic of metals, but this is not an issue with pyrolytic carbon MHV because this material is not crystalline in nature.{{Citation needed|date=October 2013}} ===Cavitation=== [[Cavitation]] is an event that can lead to MHV failure. While this has been a relatively rare occurrence, in 1988 the Edwards-Duramedics bileaflet had 46 reported failures in 20,000 implants related to cavitation damage.{{Citation needed|date=October 2013}} Since then, manufacturers have made cavitation testing an essential part of the design verification process. Cavitation is the rapid formation of vaporous microbubbles in the fluid due to a local drop of pressure below the vaporization pressure at a given temperature. When conditions for cavitation are present bubbles will form and at the time of pressure recovery they will collapse or implode. This event will cause pressure or thermal shockwaves and fluid microjets which can damage a surface. These thermodynamic conditions are known to be the cause of MHV related erosion.{{Citation needed|date=October 2013}} The valvular event that causes such cavitating conditions to exist is the closing mechanics of the MHV. Several causes of cavitation relating to valve closure have been identified. Squeeze flow is cavitation that is said to occur as the occluder approaches the housing during closure and fluid is squeezed between the occluder and the valve housing causing a low pressure formation. Water hammer is cavitation caused by the sudden stop of the valve occluder as it contacts the valve housing. This sudden retardation of the fluid retrograde inertia is said to put the fluid under tension causing cavitation. Squeeze flow is said to form a cloud of bubbles at the circumferential lip of the occluder whereas water hammer is said to be seen as transient bubbles at the occlude housing.{{Citation needed|date=October 2013}} For either event, cavitation occurs on the upstream side of valve. Clinically, cavitation is of primary concern in the mitral position. This position is especially harsh due to the sudden ventricular pressure rise which drives the valve closure against a low left atrial pressure which is said to be the worst case condition thus position for cavitation to occur. Cavitation is also suspected as a contributing factor in blood cell damage and increased risk of thromboembolic complications.{{Citation needed|date=October 2013}} The temporal rate of change of the left ventricular, measured as a slope of the ventricular pressure curve (dP/dt) is regarded as the best indicator for cavitation potential. Most MHV investigated generate cavitation only when the dP/dt is well above the physiological range. However investigations have found that several tilting disc valves and only one bileaflet valve, the Edwards-Duromedics, generate cavitation within the physiological range. Investigations have repeatedly demonstrated that bileaflet valves, with the exception of the Edwards Duramedics design, cavitate only at dP/dt levels well above the physiological range.{{Citation needed|date=October 2013}} ===Fluid mechanics=== Many of the complications associated with MHV can be explained through fluid mechanics. For example, thrombus formation is a debilitating side effect of high shear stresses created by the design of the valves. An ideal heart valve from an engineering perspective would produce minimal pressure drops, have small regurgitation volumes, minimize turbulence, reduce prevalence of high stresses, and not create flow separations in the vicinity of the valve.{{Citation needed|date=October 2013}} One measure of the quality of a valve is the effective orifice area (EOA), which can be calculated as follows: <math>EOA(\mathrm{cm}^2) = \frac{Q_{rms}}{51.6\sqrt{\Delta p}}\ </math> where <math>Q_{rms}</math> is the root mean square [[Systole (medicine)|systolic]]/[[diastolic]] flow rate (cm³/s) and <math>\Delta p</math> is the mean systolic/diastolic pressure drop ([[mmHg]]). This is a measure of how much the prosthesis impedes blood flow through the valve. A higher EOA corresponds to a smaller energy loss. The performance index (PI) normalizes the EOA by valve size and is a size-independent measure of the valve’s resistance characteristics. Bileaflet valves typically have higher PI’s than tilted-disc models, which in turn have higher PI’s than caged-ball models.{{Citation needed|date=October 2013}} As blood flows through a prosthetic heart valve, a sudden pressure drop occurs across the valve due to the reduction in cross-sectional area within the valve housing. This can be quantified through the continuity equation and Bernoulli’s equation: <math>A_1V_1 = A_2V_2</math> <math>P_1 + \frac{1}{2} \rho _1 V_1^2 = P_2 + \frac{1}{2} \rho_2 V_2^2</math> where ''A'' represents the cross-sectional area, ''P'' is [[pressure]], <math>\rho</math> is [[density]], and ''V'' is the [[velocity]].{{Citation needed|date=October 2013}} As cross-sectional area decreases in the valve, velocity increases and pressure drops as a result. This effect is more dramatic in caged-ball valves than in tilting-disc and bileaflet valves. A larger systolic pressure is required to drive flow forward in order to compensate for a large pressure drop, so it should be minimized.{{Citation needed|date=October 2013}} Regurgitation is the sum of retrograde flow during the closing motion of the valve and leakage flow after closure. It is directly proportional to valve size and is also dependent on valve type. Typically, caged-ball valves have a low amount of regurgitation as there is very little leakage. Tilting-disc and bileaflet valves are comparable, with the bileaflet valves have a slightly larger regurgitation volume. Bioprosthetics prevail over MHV in this case, as they have virtually no regurgitation volume.{{Citation needed|date=October 2013}} Turbulence and high shear stresses are also major issues with MHV, as they can fracture the valve housing or components, or induce blood damage. A large flow gradient can lead to these factors, so flow separation and stagnation should be as small as possible. High stresses are created at the edges of the annular jet in caged-ball valves, in narrow regions at the edges of the major orifice jet in tilting-disc valves, and in regions immediately distal to the valve leaflets in bileaflet valves. The implications of blood damage from these stresses are discussed in the next section.{{Citation needed|date=October 2013}} The cavitation phenomenon can also be described using fluid mechanics. This can result from pressure oscillations, flow deceleration, tip vortices, streamline contraction, and squeeze jets. This last cause is the most contributive factor to cavitation. The squeeze jets are formed when the valve is closing and the blood between the occluder and valve housing is “squeezed” out to create a high-speed jet. This in turn creates intense vortices with very low pressures that can lead to cavitation.{{Citation needed|date=October 2013}} ===Blood damage=== One of the major drawbacks of mechanical heart valves is that patients with these implants require consistent anti-coagulation therapy. Clots formed by red blood cell (RBC) and platelet damage can block up blood vessels and lead to very serious consequences. Clotting occurs in one of three basic pathways: tissue factor exposure, platelet activation, or contact activation by foreign materials, and in three steps: initiation, amplification, and propagation.{{Citation needed|date=October 2013}} In the tissue factor exposure path, initiation begins when cells are ruptured and expose tissue factor (TF). Plasma Factor (f) VII binds to TF and sets off a chain reaction which activates fXa and fVa which bind to each other to produce thrombin which in turn activates platelets and fVIII. The platelets activate by binding to the damaged tissue in the initiation phase, and fibrin stabilizes the clot during the propagation phase.{{Citation needed|date=October 2013}} The platelet activation pathway is triggered when stresses reach a level above 6 to 8 [[pascal (unit)|Pa]] (60–80 dyn/cm²). The steps involved with this are less clearly understood, but initiation begins with the binding of vWF from the plasma to GPIb on the platelet. This is followed by a large influx of Ca<sup>2+</sup> ions, which activates the platelets. GPIIb-IIIa facilitates platelet-platelet adhesion during amplification. The propagation step is still under study.{{Citation needed|date=October 2013}} Contact activation begins when fXII binds to a procoagulant surface. This in turn activates prekallikrein (PK) and high-molecular-weight kininogen (HK). Eventually, HKa-PK and HKa-fXI complexes form on the surface. In amplification, Hka-FXIa complexes activate fIX to fIXa, which in turn forms thrombin and platelets. Proteins buildup on the surface and facilitate platelet adhesion and tissue growth in the propagation stage.{{Citation needed|date=October 2013}} All MHV models are vulnerable to thrombus formation due to high shear stress, stagnation, and flow separation. The caged-ball designs experience high stresses at the walls that can damage cells, as well as flow separation due to high-velocity reverse flow surrounded by stagnant flow. Tilting-disc valves have flow separation behind the valve struts and disc as a result of a combination of high velocity and stagnant flows. The bileaflet models have high stresses during forward and leakage flows as well as adjacent stagnant flow in the hinge area. As it turns out, the hinge area is the most critical part of bileaflets and is where the thrombus formation usually prevails.{{Citation needed|date=October 2013}} In general, blood damage affects valves in both the mitral and aortic positions. High stresses during leakage flow in aortal valves result from higher transvalvular pressures, and high stresses occur during forward flow for mitral valves. Valvular thrombosis is most common in mitral prosthetics. The caged-ball model is better than the other two models in terms of controlling this problem, because it is at a lower risk for thrombosis and it is gradual when it does happen. The bileaflet is more adaptable to this problem than the tilting-disc model because if one leaflet stops working, the other can still function. However, if the hinge is blocked, both leaflets will stop functioning.{{Citation needed|date=October 2013}} Because all models experience high stresses, patients with mechanical heart valve implants require anti-coagulation therapy. Bioprosthetics are less prone to develop blood clotting, but the trade-off concerning durability generally favors their use in patients older than age 55.{{Citation needed|date=October 2013}} Mechanical heart valves can also cause [[mechanical hemolytic anemia]] with hemolysis of the [[red blood cell]]s as they pass through the valve.{{Citation needed|date=October 2013}} ==Tissue (biological) valves== ''Biological valves'' are valves of animals, like pigs, which undergo several chemical procedures in order to make them suitable for implantation in the human heart. The porcine (or pig) heart is most similar to the human heart, and therefore represents the best anatomical fit for replacement. Implantation of a porcine valve is a type of [[xenotransplantation]], also known as a xenograft, which means a transplant from one species (in this case a pig) to another. There are some risks associated with a xenograft such as the human body's tendency to reject foreign material. Medication can be used to retard this effect, but is not always successful.{{Citation needed|date=October 2013}} Another type of biological valve utilizes biological tissue to make leaflets that are sewn into a metal frame. This tissue is typically harvested from the ''Pericardial Sac'' of either cows or horses. The [[pericardial sac]] is particularly well suited for a valve leaflet due to its extremely durable physical properties. This type of biological valve is extremely effective means of valve replacement. The tissue is sterilized so that the biological markers are removed, eliminating a response from the host's immune system. The leaflets are flexible and durable and do not require the patient to take blood thinners for the rest of their life.{{Citation needed|date=October 2013}} The most used heart valves in the US, Britain and EU are those utilizing tissue leaflets. Mechanical valves are more commonly used in Asia and Latin America.{{Citation needed|date=October 2013}} The following companies manufacture tissue heart valves: Edwards Lifesciences, Medtronic, St. Jude Medical, Sorin, Medtronic ATS Medical, 3F Therapeutics, [[CryoLife]], and [[LifeNet Health]].{{Citation needed|date=October 2013}} Recently, researchers have begun working to grow heart valves in vitro. Autologous cells are seeded on a scaffold, typically made from a biodegradable polymer such as PGA or PLA. The scaffolding acts as an artificial extra-cellular matrix, guiding tissue growth into the correct 3D structure of the heart valve. Mechanical stimuli must be simulated in the culture in order to condition the tissue for physiological stress in vivo. These heart valves have not yet reached clinical trials.<ref>Neuenschwander, S., & P, H. S. (January 01, 2004). Heart valve tissue engineering. Transplant Immunology, 12, 359-365.</ref> ==Functional requirements of heart valve prostheses== The functioning of natural heart valves is characterized by many advantages: * Minimal [[Regurgitation (circulation)|regurgitation]] – This means that the amount of [[blood]] lost upstream as the valve closes is small. For example, closure regurgitation through the [[mitral valve]] would result in some blood loss from the left [[Ventricle (heart)|ventricle]] to the left [[Atrium (heart)|atrium]] as the mitral valve closes. Some degree of valvular regurgitation is inevitable and natural, up to around 5ml per beat.<ref>{{cite journal |pmid=22474745 |year=2012 |last1=Kasegawa |first1=H |last2=Iwasaki |first2=K |last3=Kusunose |first3=S |last4=Tatusta |first4=R |last5=Doi |first5=T |last6=Yasuda |first6=H |last7=Umezu |first7=M |title=Assessment of a novel stentless mitral valve using a pulsatile mitral valve simulator |volume=21 |issue=1 |pages=71–5 |journal=The Journal of heart valve disease}}</ref> However, several heart valve pathologies (e.g. rheumatic [[endocarditis]]) may lead to clinically significant valvular regurgitation. A desirable characteristic of heart valve prostheses is that regurgitation is minimal over the full range of [[physiological]] heart function (i.e. complete functional envelope of [[cardiac output]] vs. [[heart rate]]). * Minimal transvalvular pressure gradient – Whenever a [[fluid]] flows through a restriction, such as a valve, a [[pressure]] [[gradient]] arises over the restriction. This pressure gradient is a result of the increased resistance to flow through the restriction. Natural heart valves have a low transvalvular pressure gradient as they present little obstruction to the flow through themselves, normally less than 16 mmHg. A desirable characteristic of heart valve prostheses is that their transvalvular pressure gradient is as small as possible. * Non-[[thrombosis|thrombogenic]] – As natural heart valves are lined with an [[endothelium]] continuous with the endothelium lining the heart chambers they are not normally thrombogenic. This is important as should [[thrombus|thrombi]] form on the [[heart valve leaflets]] and become seeded with [[bacteria]], so called "[[bacterial vegetation]]s" will form. Such vegetations are difficult for the body to deal with as the normal [[physiology|physiological]] defense mechanisms are not present within the valve leaflets because they are [[Blood vessel|avascular]] and largely composed of [[connective tissue]] (Fixme: Create article discussing the pathgonesis of leaflet bacterial vegetations.). Should bacterial vegetations form on the valve leafets they may continually seed [[bacteria]] into the [[arterial tree]] which may lead to [[bacteremia]] or [[septicaemia]]. Portions of the vegetation may also break off forming [[Embolism|septic emboli]]. Septic emboli can lodge anywhere in the [[arterial tree]] (e.g. [[brain]], [[bowel]], [[lungs]]) causing local infectious [[Focus (geometry)|foci]]. Even dislodged fragments from uninfected thrombi can be hazardous as they can lodge in, and block, downstream [[artery|arteries]] (e.g. [[coronary artery|coronary arteries]] leading to [[myocardial infarction]], [[cerebral arteries]] leading to [[stroke]], see [[embolism]]). A desirable characteristic of heart valve prostheses is that they are non or minimally thrombogenic. * Self-repairing – Although of limited extent compared to well vascularised tissue (e.g. [[muscle]]), the valve leaflets do retain some capacity for repair due to the presence of regenerative [[cell (biology)|cells]] (e.g. [[fibroblasts]]) in the [[connective tissue]] from which the leaflets are composed. As the human heart beats approximately 3.4x10<sup>9</sup> times during a typical human lifespan this limited but nevertheless present repair capacity is critically important. No heart valve prostheses can currently self-repair but replacement tissues grown using [[stem cell]] technology may eventually offer such capabilities.{{Citation needed|date=October 2013}} * Rapid dynamic response – STD ==Design challenges of heart valve prostheses== [[Image:BiologicalValves.JPG|thumb|150px|A replaceable model of Cardiac Biological Valve Prosthesis.<ref name="dedalus">{{cite journal |last1=Lyra |first1=R. M. |last2=Leirner |first2=A. A. |last3=Pomerantzeff |first3=Pablo Maria Alberto |last4=Nyashida |first4=S. |last5=Jatene |first5=Adib |title=Estudo in vitro, de uma bioprotese recambiavel |trans-title=In vitro study of a recambiavel bioprosthesis |language=Portuguese |journal=Revista da Sociedade de Cardiologia do Estado de São Paulo |volume=2 |issue=2 Suppl B |pages=71 |year=1992}}</ref> <ref name="dedalus_a">{{cite journal |last1=Lyra |first1=R. M. |last2=Leirner |first2=A. A. |last3=Pomerantzeff |first3=Pablo Maria Alberto |last4=Hyashida |first4=S. |last5=Jatene |first5=Adib |title=Novo modelo de bioprotese recambiavel |trans-title=New model of recambiavel bioprosthesis |journal=Arquivos Brasileiros de Cardiologia |volume=59 |issue=Suppl 2 |pages=221 |year=1992}}</ref>]] * Thrombogenesis / haemocompatibility ** Mechanisms: *** Forward and backward flow shear *** Static leakage shear *** Presence of foreign material (i.e. intrinsic coagulation cascade) *** Cellular maceration * Valve-tissue interaction * Wear * Blockage * Getting stuck * Dynamic responsiveness * Failure safety * Valve orifice to anatomical orifice ratio * Trans-valvular pressure gradient * Minimal leakages * Detachable And Replaceable Models Of Heart Valve Prostheses ==Replaceable models of heart valve prostheses== Mechanical or biological (bioprostheses or "tissue valves"), '''the replaceable models of implantable heart valve prostheses''' are made by two or three mechanical components. The gear attachment mechanism usually uses the coil effect or the bayonet coupling system.{{Citation needed|date=October 2013}} '''The replaceable models of implantable heart valve prostheses''' are typically supplied with a sewing or suturing ring surrounding the valve body or stent that is to be sutured by the surgeon to the valvar rim.{{Citation needed|date=October 2013}} The biggest challenge in this type of prostheses is the difficulty in its future removal. This is due to the formation of pannus fibrotic around the valve body and sewing ring. To separate the parts is very laborious, keeping intact the sewing ring, which will be used in the coupling of the new valve. To easily remove the old replaceable bioprostheses, its "stent" can be sectioned to dismount its framework and so facilitate its removal from the sewing ring.{{Citation needed|date=October 2013}} <gallery> File:The replaceable model of implantable heart valve bioprosthese de Menezes Lyra R 1992.tif </gallery> Time line of the detachable and replaceable models of heart valve prostheses: * 1984 Martin, J. R <ref>{{cite journal |last1=Martin |first1=J. R |last2=Grassi |first2=E. D |last3=Barone |first3=A |last4=Milei |first4=J |last5=Barone |first5=H. D. |title=Protesis valvular cardiaca desmontable. Implante experimental 'in vivo' y resustitucion valvular alejada |trans-title=Dismountable heart valve prosthesis. In vivo experimental implant and delayed valvular replacement |language=Portuguese |journal=Revista Argentina de Cirugía |volume=46 |issue=6 |pages=275–6 |year=1984}}</ref> * 1984 Martin, J. R <ref>{{cite journal |last1=Martin |first1=J. R |last2=Barone |first2=H. D |last3=Barone |first3=A |last4=Milei |first4=J |last5=Grassi |first5=E. D. |title=Anel portador de valvulas cardiacas |trans-title=Ring porter of cardiac valves |language=Portuguese |journal=Arquivos brasileiros de cardiologia |volume=43 |issue=6 |pages=415–21 |year=1984 |pmid=6399678 |url=http://www.arquivosonline.com.br/pesquisartigos/Pdfs/1984/v43n6/43060007.pdf}}</ref> * 1984 Martin, J. R <ref>{{cite journal |last1=Martin |first1=J. R |last2=Grassi |first2=E. D |last3=Barone |first3=A |last4=Barone |first4=H. D |last5=Patane |first5=A. M. |title=Protesis valvular cardiaca demontable Desarrollo experimental (Prototipo I) |trans-title=Dismountable heart valve prosthesis.Experimental development (Prototype I) |language=Portuguese |journal=Revista Argentina de Cirugía |volume=46 |issue=6 |pages=272–4 |year=1984}}</ref> * 1987 Fernandez J <ref>{{cite journal |pmid=15227327 |year=1987 |last1=Fernandez |first1=J |last2=Gonzalez-Lavin |first2=L |last3=Maranhao |first3=V |last4=Yang |first4=SS |title=A new bioprosthesis for aortic and mitral valve replacement: Preliminary evaluation of the Tascon valve |volume=14 |issue=1 |pages=31–8 |pmc=324690 |journal=Texas Heart Institute journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital}}</ref> * 1988 Cooper DK <ref>{{cite journal |doi=10.1016/S0003-4975(10)64532-8 |title=Initial Experimental Experience with a 'Replaceable' Cardiac Valve Prosthesis |year=1988 |last1=Cooper |first1=D.K.C. |last2=Wicomb |first2=W.N. |last3=Gould |first3=Gwyneth M. |last4=Boonzaier |first4=D. |journal=The Annals of Thoracic Surgery |volume=45 |issue=5 |pages=554–8 |pmid=3365047}}</ref> * 1992 Lyra, R M <ref name="dedalus" /> * 1992 Lyra, R M <ref name="dedalus_a" /> * 1992 Jansen J <ref>{{cite journal |doi=10.1111/j.1525-1594.1992.tb00313.x |title=Detachable Shape-Memory Sewing Ring for Heart Valves |year=2008 |last1=Jansen |first1=Josef |last2=Willeke |first2=Sebastian |last3=Reul |first3=Helmul |last4=Rau |first4=Günter |journal=Artificial Organs |volume=16 |issue=3 |pages=294–7 |pmid=10078262}}</ref> ==Typical configuration of a heart valve prosthesis== * Anchor * Leaflets ==History== [[File:Hufnagel heart Valve15111214-photos 309.jpg|thumb|upright|Hufnagel heart Valve]] In the 1950s, Dr. [[Charles A. Hufnagel]] developed an artificial heart valve. His mechanical valve consisted of two parts, a ball that is surrounded by a cage which is the first variation of the ball-in-cage valves. Originally, the cage and the ball were constructed using [[Plexiglas]]. Due to the noise created by the contacts between the moving ball and the cage, the ball was later changed to use [[silicone]]-coated material. The first implantation of mechanical heart valve to human was performed by Dr. Hufnagel on September 11, 1952, using the valve that he developed. This event accelerated the development of other artificial heart valves.<ref>{{cite journal|last1=Butany|first1=J|last2=Ahluwalia|first2=MS|last3=Fayet|first3=C|last4=Munroe|first4=C|last5=Blit|first5=P|last6=Ahn|first6=C|title=Hufnagel valve: the first prosthetic mechanical valve.|journal=Cardiovascular Pathology|date=2002|volume=11|issue=6|pages=351–3|pmid=12459437|doi=10.1016/s1054-8807(02)00132-1}}<!--|accessdate=8 March 2015--></ref> ==Additional images== <gallery> File:Blausen 0056 ArtificialHeartValve.png|3D Rendering of Mechanical Valve File:Blausen 0057 ArtificialHeartValve StFrancis.png|3D Rendering of Mechanical Valve (St. Francis model) </gallery> ==See also== * [[Artificial heart]] == References == {{Reflist}} == Further reading == * {{cite journal |pmid=7392405 |year=1980 |last1=Bendet |first1=IaA |title=Psychological aspects of the rehabilitation of patients after the surgical treatment of heart defects |last2=Morozov |first2=SM |last3=[[:fr:Victor Skumin|Skumin]]|first3=VA |script-title=ru:Психологические аспекты реабилитации больных после хирургического лечения пороков сердца |trans-title=Psychological aspects of the rehabilitation of patients after the surgical treatment of heart defects |language=Russian |volume=20 |issue=6 |pages=45–51 |journal=Kardiologiia}} * {{cite journal |pmid=259874 |year=1979 |last1=[[:fr:Victor Skumin|Skumin]] |first1=VA |title=Nurse's role in medico-psychological rehabilitation of patients with artificial heart valves |volume=38 |issue=9 |pages=44–5 |journal=Meditsinskaia Sestra}} * {{cite journal |pmid=6758444 |year=1982 |last1=[[:fr:Victor Skumin|Skumin]]|first1=VA |title=Nonpsychotic mental disorders in patients with acquired heart defects before and after surgery (review) |volume=82 |issue=11 |pages=130–5 |journal=Zhurnal nevropatologii i psikhiatrii imeni S.S. Korsakova}} *{{cite journal |pmid=2911200 |year=1989 |last1=Klepetko |first1=W |last2=Moritz |first2=A |last3=Mlczoch |first3=J |last4=Schurawitzki |first4=H |last5=Domanig |first5=E |last6=Wolner |first6=E |title=Leaflet fracture in Edwards-Duromedics bileaflet valves |volume=97 |issue=1 |pages=90–4 |journal=The Journal of Thoracic and Cardiovascular Surgery}} *{{cite journal |pmid=9605082 |year=1998 |last1=Podesser |first1=BK |last2=Khuenl-Brady |first2=G |last3=Eigenbauer |first3=E |last4=Roedler |first4=S |last5=Schmiedberger |first5=A |last6=Wolner |first6=E |last7=Moritz |first7=A |title=Long-term results of heart valve replacement with the Edwards Duromedics bileaflet prosthesis: A prospective ten-year clinical follow-up |volume=115 |issue=5 |pages=1121–9 |journal=The Journal of Thoracic and Cardiovascular Surgery |doi=10.1016/s0022-5223(98)70412-x}} * Knapp RJ, Daily JW, Hammitt FG. 1970. Cavitation. New York: McGraw-Hill Int. Book Co. *{{cite journal |pmid=12893035 |year=2003 |last1=Lim |first1=WL |last2=Chew |first2=YT |last3=Low |first3=HT |last4=Foo |first4=WL |title=Cavitation phenomena in mechanical heart valves: The role of squeeze flow velocity and contact area on cavitation initiation between two impinging rods |volume=36 |issue=9 |pages=1269–80 |journal=Journal of Biomechanics |doi=10.1016/s0021-9290(03)00161-1}} *{{cite journal |pmid=7798287 |year=1994 |last1=Bluestein |first1=D |last2=Einav |first2=S |last3=Hwang |first3=NH |title=A squeeze flow phenomenon at the closing of a bileaflet mechanical heart valve prosthesis |volume=27 |issue=11 |pages=1369–78 |journal=Journal of Biomechanics |doi=10.1016/0021-9290(94)90046-9}} *{{cite journal |pmid=2045192 |year=1991 |last1=Graf |first1=T |last2=Fischer |first2=H |last3=Reul |first3=H |last4=Rau |first4=G |title=Cavitation potential of mechanical heart valve prostheses |volume=14 |issue=3 |pages=169–74 |journal=The International journal of Artificial Organs}} *{{cite book |last1=Kafesjian |first1=R |last2=Wieting |first2=DW |last3=Ely |first3=J |last4=Chahine |first4=GL |last5=Frederick |first5=GS |last6=Watson |first6=RE |year=1990 |chapter=Characterization of Cavitation Potential of Pyrolitic Carbon |pages=509–16 |editor1-first=Endré |editor1-last=Bodnar |title=Surgery for Heart Valve Disease: Proceedings of the 1989 Symposium |publisher=ICR |isbn=978-1-872743-00-4}} *{{cite journal |pmid=8665016 |year=1996 |last1=Chahine |first1=GL |title=Scaling of mechanical heart valves for cavitation inception: Observation and acoustic detection |volume=5 |issue=2 |pages=207–14; discussion 214–5 |journal=The Journal of Heart Valve Disease}} *{{cite journal |pmid=8944940 |year=1996 |last1=Zapanta |first1=CM |last2=Stinebring |first2=DR |last3=Sneckenberger |first3=DS |last4=Deutsch |first4=S |last5=Geselowitz |first5=DB |last6=Tarbell |first6=JM |last7=Synder |first7=AJ |last8=Rosenberg |first8=G |last9=Weiss |first9=WJ |last10=Pae |first10=WE |last11=Pierce |first11=WS |title=In vivo observation of cavitation on prosthetic heart valves |volume=42 |issue=5 |pages=M550–5 |journal=ASAIO Journal |doi=10.1097/00002480-199609000-00047}} *{{cite journal |pmid=8061875 |year=1994 |last1=Richard |first1=G |last2=Beavan |first2=A |last3=Strzepa |first3=P |title=Cavitation threshold ranking and erosion characteristics of bileaflet heart valve prostheses |volume=3 Suppl 1 |pages=S94–101 |journal=The Journal of Heart Valve Disease}} ==External links== *[https://web.archive.org/web/20061113095223/http://www.mayoclinic.org/heart-valve-surgery/treatment.html Page describing types of heart valve replacements] *{{cite web |url=http://www.sciencedaily.com/releases/2011/11/111122113212.htm |title=New Design for Mechanical Heart Valves |date=November 23, 2011 |publisher=ScienceDaily}} {{Medicine}} [[Category:Cardiology]] [[Category:Cardiac surgery]] [[Category:Implants (medicine)]] [[Category:Prosthetics]]'
Whether or not the change was made through a Tor exit node (tor_exit_node)
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Unix timestamp of change (timestamp)
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