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`REVIEW
`Analysis of prosthetic cardiac devices: a guide for the
`practising pathologist
`J Butany, M J Collins
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`J Clin Pathol 2005;58:113–124. doi: 10.1136/jcp.2004.020271
`
`Pathologists all over the world increasingly encounter
`prosthetic cardiac devices. A good evaluation of these
`devices is a valuable source of information, which can
`contribute to patient care and the appreciation and
`understanding of the pathobiology involved in the changes
`occurring between the host and the implanted prosthetic
`device. This article summarises the considerations
`underlying the analysis of prosthetic devices (particularly
`prosthetic heart valves), including the identification of the
`devices, the major morphological features of the devices,
`their modes of failure, and some technical details about
`evaluation and pitfalls.
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`P rosthetic cardiac devices improve survival
`
`life
`and greatly increase the quality of
`in most patients.1 Despite considerable
`advances in the technology behind prosthetic
`devices, these devices are still far from perfect,
`and ongoing changes continue to be made in an
`effort to enhance their function, effectiveness,
`and life expectancy.2 Detailed evaluation of
`explanted devices (failed or still functional) can
`contribute to the future care of patients needing
`these devices,
`in addition to establishing the
`mechanisms of change and the pathobiology of
`failure of these devices. Many of these devices
`are still not ‘‘perfect’’. In the case of new devices
`(new coronary and aortic stents) or modifica-
`tions to devices that have been in use for some
`time, we suggest that the device should be
`referred to colleagues with the facilities and
`interest necessary for detailed analysis, or to the
`manufacturers, who will probably conduct a
`thorough and exhaustive analysis. Ongoing
`evaluation will also help to define the structural
`features of those devices that are most important
`and which are most beneficial
`to the host.
`Understanding these features may help to pre-
`dict
`the modifications needed in the future
`development of these devices,
`in an effort to
`improve their safety and durability. We present a
`brief summary of the approach to the analysis of
`prosthetic cardiovascular devices, followed by a
`more detailed description and analysis of differ-
`ent devices.
`
`change and the pathobiology of failure of
`these devices’’
`
`We will emphasise the following: (1) the
`objectives of evaluation, (2) the techniques of
`evaluation, and (3) the use of technical and other
`data in the necropsy/surgical pathology evalua-
`tion of prosthetic devices in individual patients.
`Because prosthetic heart valves (PHVs) have
`been in use for a considerably longer period than
`most other devices, a more detailed analysis of
`these is presented.
`
`Objectives of the analysis of prosthetic
`cardiac devices
`The pathologist at the surgical pathology bench
`today often sees prosthetic cardiovascular devices
`that surgeons have explanted, or they may be
`seen at the time of necropsy (table 1). The
`detailed and complete examination of
`these
`devices can provide invaluable information. The
`collected information should include the follow-
`ing:
`(1)
`the type of device used and its
`manufacturer; (2) documentation of the types
`of changes seen in the device, such as structural
`deterioration,
`calcification, or pannus over-
`growth; and (3) correlation of the morphological
`features in the explanted device with the clinical
`features, to provide a basis for an explanation of
`dysfunction—that
`is, occlusion,
`stenosis, or
`incompetence, or device failure.
`In any one
`patient, the determination of the cause of failure
`may contribute to subsequent management,
`particularly when (1) a diagnosis of infection
`(infective endocarditis in the case of PHVs) is
`made, which would necessitate a course of
`appropriate antibiotic treatment for the micro-
`organism seen; (2) the presence of a thrombus is
`noted on a prosthetic device, which might
`convince the surgeon of the need to initiate
`immediate anticoagulant treatment.
`The analysis of a series of explanted devices
`will allow the rates and modes of failure to be
`defined, and the specific modes of failure of
`particular devices to be characterised. The clinical
`pathological
`examination and
`analysis
`of
`explanted devices, either new devices or mod-
`ified devices, allows correlations and the compi-
`lation of data based on human experience, often
`far different than that obtained from the initial
`animal studies. The analyses also allow the
`biocompatibility of the host and the materials
`composing the device to be defined. In some
`instances, the establishment of timeframes of
`
`See end of article for
`authors’ affiliations
`. . . . . . . . . . . . . . . . . . . . . . .
`
`Correspondence to:
`Dr J Butany, Department of
`Pathology E4-322, Toronto
`General Hospital, Toronto,
`ON M5G 2C4, Canada;
`jagdish.butany@uhn.on.ca
`
`Accepted for publication
`2 August 2004
`. . . . . . . . . . . . . . . . . . . . . . .
`
`‘‘Detailed evaluation of explanted devices
`(failed or still functional) can contribute to the
`future care of patients needing these devices,
`Abbreviations: BHV, bioprosthetic heart valve; MHV,
`in addition to establishing the mechanisms of
`mechanical heart valve; PHV, prosthetic heart valve
`NORRED EXHIBIT 2280 - Page 1
`Medtronic, Inc., Medtronic Vascular, Inc.,
`& Medtronic Corevalve, LLC
`v. Troy R. Norred, M.D.
`Case IPR2014-00395
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`Table 1 Prosthetic cardiovascular devices
`
`may arise, including the sites at which thrombus may be
`initiated.
`
`‘‘The observed failure modes and mechanisms help in the
`development of improved and new devices’’
`
`these findings can help a pathologist
`Knowledge of
`involved in the examination of devices from preclinical
`animal studies (for example, materials implanted in large
`animals), and can also provide expert evidence in medical
`legal cases related to device failure. In many, if not most,
`countries where devices are implanted, the state often has
`rules and regulations pertaining to the reporting of device
`related clinical problems and complications. In the USA, this
`is specified in the Safe Medical Devices Act of 1990 (PL101–
`619),3 and in Canada is mandated by the health protection
`branch of the Federal Ministry of Health and in the UK by the
`equivalent section at
`the Ministry of Health.
`In many
`jurisdictions, the law requires the reporting of device related
`deaths, serious illnesses, and injuries, by all health care
`personnel aware of the same, to the appropriate authorities or
`the manufacturers or both, depending on the nature of the
`incident. Any pathologist who makes this initial discovery of
`harm or damage relatable to a medical device malfunction
`should initiate this reporting process.
`The reporting of
`findings in prosthetic cardiovascular
`devices necessitates some knowledge about the devices, their
`identifying features, and the established and potential failure
`modes of those devices used under particular circumstances
`at particular sites. Knowledge of the clinical data is usually
`helpful in making appropriate clinical–pathological correla-
`tions. In each situation, several generic types and many
`models of prosthetic devices have been used, and in some
`situations continue to be used.4 5 Many have long since been
`
`Cardiac
`
`(1) Prosthetic heart valves
`Bioprosthesis
`Mechanical prosthesis
`Bentall grafts (conduit with
`prosthesis)
`(2) Annuloplasty rings
`(3) Synthetic sutures
`For bypass grafts
`For artificial chordae tendineae
`(4) Pacemaker leads
`(5) Defibrillator leads
`(6) Tissue patches
`(7) Ventricular assist devices (rare)
`(8) Artificial hearts (rare)
`
`Vascular
`
`(1) Synthetic grafts
`Dacron
`PTFE
`
`(2) Tissue patches (pericardial)
`(3) Synthetic patches
`
`(4) Vascular stents
`(5) Endovascular devices
`
`failure allows a
`occurrence of pathological evidence of
`correlation to be made with abnormalities noted on clinical
`investigation (such as echocardiography, computerised tomo-
`graphic scan, or magnetic resonance imaging), and helps
`decide the time and situations in which intervention is
`warranted.
`In addition, the observed failure modes and mechanisms
`help in the development of improved and new devices.
`Although relatively few devices are obtained before failure,
`when they are obtained at necropsy or at heart transplant,
`these devices do allow the establishment of morphological
`features at intermediate timeframes, before the development
`of overt failure. One may then speculate on the rate of
`progression of changes and the clinical and pathological
`features of devices that have functioned well, and obtain
`some idea of the sites where problems, such as failure modes,
`
`1.
`
`Demographic/relevant clinical data
`
`2.
`
`Photography: all surfaces
`
`3.
`
`Radiology, of all devises to
`Confirm presence (or absence) and extent of calcification
`(i)
`Identify the device
`(ii)
`Determine device integrity – exclude fractures of metal struts
`(iii)
`Examine endovascular stents (need multiplane x rays)
`(iv)
`
`4.
`
`Dimensions: external and internal
`
`5.
`
`Gross description: special emphasis on
`Appearance, normal/abnormal
`(i)
`Presence of thrombus/blood
`(ii)
`Host tissue (pannus), extent
`(iii)
`Vegetation(s): colour, size, site, fixation, friability
`(iv)
`(vi)
`Tissue valves
`Mechanical valves:
`(v)
`Shape
`(a)
`Note asymmetry
`(a)
`Colour
`(b)
`Irregularity
`(b)
`Location
`(c)
`Cracks and fractures
`(c)
`Calcific deposits
`(d)
`Mobility of components
`(d)
`Cusp tears
`(e)
`Mobility of the cusps
`(f)
`Appearance of commissural regions
`(g)
`
`(vii)
`
`Stents or tube grafts
`Lumen size
`(a)
`Presence of thrombus
`(b)
`Degree of stenosis of lumen
`(c)
`
`6.
`
`Tissues for histology
`Common stains
`(i)
`Stain for microorganisms
`(a)
`Stain for connective tissue
`(b)
`Stain for calcium
`(c)
`
`(ii)
`
`Mechanical valves
`Vegetations
`(a)
`Pannus and underlying sewing cuff
`(b)
`
`(iii)
`
`Tissue valves
`Parts of cuspal tissue (longitudinal sections)
`(a)
`Porcine aortic commissural region
`(b)
`Any tissue adherent to device
`(c)
`Thrombus of any age (note location)
`(d)
`
`Figure 1 Gross examination of prosthetic heart devices: essential steps.
`
`www.jclinpath.com
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`Figure 2 Detailed examination of
`prosthetic heart valves. *For special
`investigations only. Adapted from
`Schoen.2 CT, computed tomography.
`
`Autopsy specimen
`
`Surgical: excised prosthesis
`
`Examine heart with prosthesis in situ
`
`Dissect/expose prosthesis
`
`Remove prosthesis/es
`
`Gross examination (fig 1)
`
`Mechanical HVP
`
`Bioprosthesis
`
`• Detailed examination of
`° Hinge areas
`° Pannus and relation to valve ring
`° Histology-thrombus/pannus
` other adherent tissues
`
`• Examination with dissection microscopy
`
`• Scanning electron microscopy
`
`A.
`
`Detach biological tissues from stent and fabric
`• Radiology
`• Examination of tissues
`° Histology
`° Electron microscopy
` (a) Transmission
` (b) Scanning
`
`B.
`
`Examination of entire valve
`Special sections:
`• Plastic (methylmethacrylate) embedding
`• Section with diamond lathe
`• Polish and stain surface of thick sections
`
`C.
`
`Small specimen CT scan (for non-destructive
`evaluation)
`
`replaced by newer devices, which are now more widely in
`use. However, many pathologists will continue to encounter
`the ‘‘obsolete’’ devices. Therefore, it is essential to have some
`knowledge of the structure and pathology of these older
`devices, in addition to those that are currently implanted.
`
`At any institution where considerable numbers of cardio-
`vascular devices are implanted and explanted, it is worth-
`while to establish a protocol for the analysis of these devices,
`in consultation with the physicians who implanted/explanted
`the device. Later analysis of these data is considerably easier
`when a protocol is followed, and allows better identification
`of complications, tissue biomaterials, and patient device
`interactions. The protocol should include pathological exam-
`inations such as gross and dissecting microscopic examina-
`tion, specimen photography,
`radiology, and histological
`analysis (figs 1, 2). Other methods of analysis, such as
`embedding the devices in different synthetic materials (for
`example, methylmethacrylate) and electron microscopy,
`require equipment usually available in biomaterials research
`facilities or at
`the manufacturer’s own facilities. The
`principles of examination of explanted cardiovascular devices
`have been reported previously.2 Contemporary cardiovascular
`devices are numerous and a brief listing is offered in table 1.
`The general approach to all of these explanted devices should
`be the same (fig 1). The devices to be discussed in this paper
`will include PHVs and endovascular devices (table 1). Figure 1
`shows the general protocol to be followed in the examination
`of explanted prosthetic cardiovascular devices. Other similar
`protocols are also available.4–8
`
`‘‘At any institution where considerable numbers of
`cardiovascular devices are implanted and explanted, it is
`worthwhile to establish a protocol for the analysis of these
`devices’’
`
`Figure 3 (A) Anteroposterior and (B) lateral x rays of a Starr-Edwards
`mechanical valve (Model 1000) shows the intact ‘‘three leg cage’’.
`(C) Flow surface and (D) non-flow surface of a ‘‘four leg cage’’
`Starr-Edwards (Model 6400) valve. The struts are intact and the occluder
`(or poppet) has a pale yellow/brown colour. The non-flow surface shows
`tissue (arrows) still adherent to the sewing cuff.
`
`Prosthetic heart valves
`PHVs may be mechanical (MHV) (figs 3–7) or biological
`(BHV) (figs 8-11).4 5 9 10 All PHVs have a passive mode of
`functioning, opening and closing are responses to pressure
`and flow changes within the heart. MHVs are made of
`
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`Figure 4 Bjork-Shiley concavo-convex valve. (A) x Ray of profile
`(lateral) view and (B) anteroposterior view showing the large (inflow)
`strut and the small (outflow) strut. Gross appearance of the valve;
`(C) valve partially closed with the disc in the oblique position and
`(D) valve open (disc or occluder is nearly vertical).
`
`non-physiological materials with a mobile occluder, which is
`usually made of fairly rigid materials. BHVs are in reality a
`combination of tissue and synthetic biomaterials, with the
`tissue itself being flexible, and today made up largely of
`porcine aortic valves or bovine pericardium. The appearance
`and functioning of tissue valves is generally similar to native
`heart valves. The major types of cardiac valvular replacement
`devices that are used fairly widely are: caged ball devices (for
`example, Starr-Edwards ball in cage prosthesis; fig 3); the
`caged disc prosthesis (for example, the Beall valve); tilting
`disc valves (for example, Bjork-Shiley valves; figs 4, 5);
`bileaflet tilting disc valves (for example, St Jude Medical
`valves; figs 6, 7); tissue valves (for example, Medtronic (or
`Hancock) porcine valves, Carpentier-Edwards (porcine or
`pericardial) valves; figs 8–11); and other similar devices and
`stentless tissue valves. Prosthetic heart valves have many
`complications. It
`is useful
`to be aware of
`these when
`examining a heart with a prosthetic valve in place (fig 12).
`
`MECHANICAL HEART VALVE PROSTHESES
`These are prosthetic heart valves that are made entirely of
`synthetic materials. These devices have thrombogenic poten-
`tial and patients who have these devices implanted have to be
`maintained on lifelong anticoagulants. These devices have
`three major parts, namely: (1) the occluder—this may be a
`ball (or poppet), a disc, or a hemidisc; (2) the superstructure,
`which holds the occluder in place, generally with a cage-like
`appearance; and (3) the valve base or housing with a fabric
`sewing ring.11
`Although numerous MHV prostheses have been designed
`and used over the years, among the most widely used have
`been the Starr-Edwards ball in cage valve (fig 3), the Bjork-
`Shiley valve (figs 4, 5), the Medtronic Hall tilting disc valve,
`the St Jude Medical bileaflet valve (fig 7), and the
`CarboMedics bileaflet valve (fig 6). The ball in cage valve,
`among the first MHVs to be used, is still manufactured and
`sold in some regions of the world—although only in small
`numbers (Edwards Life Sciences, personal communication,
`
`Figure 5 (A) x Ray (anteroposterior) of a Bjork-Shiley Monostrut valve.
`(B) Outflow surface showing the single outflow strut and (C) inflow
`surface of the Bjork-Shiley monostrut valve. The struts and the disc are
`intact.
`
`the disc in cage valves, which had a
`2004). However,
`biconvex disk, are no longer available. MHVs are constructed
`largely of either pure titanium (for example, the Medtronic
`Hall valve) or chromium cobalt alloys (for example, the Starr-
`Edwards and the Bjork-Shiley valves), or of graphite. The
`leaflets of bileaflet valves are made of graphite coated with
`pyrolytic carbon, which provides a smooth, strong, fatigue
`resistant, and highly thromboresistant surface. All PHVs have
`a fabric sewing ring and a stent. The sewing ring allows the
`surgeon to anchor the valve in place at the valve site and
`the valve stent or housing is for anchoring the tissue or the
`
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`Figure 7 (A, B) x Rays of the flow surface and profile of the St Jude
`Medical bileaflet prosthesis. Views of a St Jude Medical bileaflet
`prosthesis with (C) the leaflets open and (D) the leaflets closed. A thick
`layer of grey/white pannus is seen on the flow and the non-flow surfaces
`of the sewing ring.
`
`Xenografts are made from aldehyde preserved animal
`tissues, which are cleaned, sized, and mounted on a fabric
`covered prosthetic frame or stent.4 7 8 The preservative for
`these tissues is glutaraldehyde. Different manufacturers use
`varying strengths of glutaraldehyde. The prosthetic frame is
`made up of posts or struts and the intervening valve ring.
`Pericardial bioprostheses have also been fairly widely used
`and in this type of BHV the cusps are made of three pieces of
`glutaraldehyde treated bovine parietal pericardium. This is
`
`Figure 8 (A, B) Anteroposterior and lateral x rays of a Hancock
`porcine valve show a radio opaque valve ring and small eyelets in each
`of the stent posts. (C) The flow surface and (D) the non-flow surface of the
`porcine valve. The cusps are soft, pliable, and intact.
`
`NORRED EXHIBIT 2280 - Page 5
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`Figure 6 (A–C) x Rays of a Carbomedics bileaflet valve prosthesis with
`the discs open, discs closed, and profile of the prosthesis, respectively;
`x rays also show the radio opaque prosthesis housing. (D) The flow
`surface (discs open) and (E) the non-flow surface of the Carbomedics
`bileaflet prosthesis. The flow and non-flow surfaces of the sewing cuff are
`carbon coated (black).
`
`mechanical parts of the valve. Both cause some degree of
`obstruction at the valve orifice, and in many instances, this is
`a condition that they were meant to treat.
`
`‘‘Today, autografts (the patient’s own pulmonary valve),
`are excised and grafted into the aortic root, and a
`homograft placed in the pulmonary site’’
`
`Bioprosthetic heart valves (BHVs) (figs 8–11), or tissue
`valves (or xenografts) as they are commonly called, look very
`much like native aortic valves except that the implanted valve
`is attached to a prosthetic frame, making its commissural and
`infracommissural regions more rigid.6 BHVs are of two main
`categories: (1) heterografts or xenografts, such as porcine
`aortic valves or bovine pericardial valves; and (2) homografts
`or allografts, such as aortic or pulmonic valves primarily from
`human cadavers. These may both have the aortic or pulmonic
`arterial tissues attached to them as a conduit. Among the
`newest types of BHVs are autografts. In the past, these
`autografts were made of fascia latta or native pericardium.
`Today, autografts (the patient’s own pulmonary valve), are
`excised and grafted into the aortic root, and a homograft
`placed in the pulmonary site.
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`Figure 9 Anteroposterior and lateral x rays of an Ionescu-Shiley
`pericardial bioprosthesis showing the valve ring in three parts. Two of
`the three cusps show radio opaque areas of calcification (arrows).
`(C) The flow surface and (D) the non-flow views of an Ionescu-Shiley
`bovine pericardial valve. Pannus (arrows) is seen on the flow surface.
`
`attached to or mounted on a frame. Detailed descriptions of
`these HVPs are available.4 8 Allografts are the other type of
`‘‘bioprosthesis’’, and are derived from cadavers or from hearts
`explanted for transplantation. Many of these come with the
`aortic root attached (root graft). Most are cryopreserved and
`therefore the tissue is not crosslinked; that is, it has not been
`treated with aldehydes. These are transplanted directly into
`the aortic root, without benefit of a supporting synthetic
`frame.
`
`Figure 10 Anteroposterior and lateral x rays of a Carpentier-Edwards
`porcine bioprosthesis. (C) The flow surface and (D) the non-flow surface
`of a Carpentier-Edwards porcine valve. The cusps are pliable and intact.
`However, all three commissural regions show detachment from the stent
`posts.
`
`Figure 11 (A) The flow surface and (B) the non-flow surface of a
`Carpentier-Edwards pericardial bioprosthesis. The cusps are soft,
`pliable, intact, and they co-apt well.
`
`The shape of the prosthesis should be noted with special
`regard to the stent. Stent posts should normally be vertical.
`Any move away from the vertical, especially towards the
`orifice of the device, will probably have developed after
`implantation. This would lead to sagging of the bioprosthesis
`cusps and to dysfunction. This inward flexion or bending is
`known as ‘‘stent creep’’, and is seen in some porcine
`bioprostheses, especially the older models. The presence of
`any surgical sutures around stent posts must be noted.
`Occasionally, surgical sutures meant to anchor the prosthesis
`to the native valve annulus get hooked over stent posts
`(mitral site). If this happens, at least two of the cusps become
`trapped or fixed in position at their commissural regions and
`become dysfunctional,
`leading to valvular incompetence,
`and if not corrected immediately, this leads to cusp tears and
`calcification. This complication should be rare today because
`the manufacturer supplies the BHV with sutures connecting
`the three stent post tips, the suture being snipped immedi-
`ately after the prosthesis has been implanted in place.
`Attention should be paid to the appearance of the device,
`especially with some idea of the normal design in mind, so
`that any flaws detected can be recorded. These flaws may
`relate to design, preimplantation or postimplantation stres-
`ses, surgical sutures, abrasion damage to biological materials
`adjacent to synthetic materials, and the stasis of blood—that
`is, thrombosis. Many of the current generation of BHVs have
`the cusp tissue components treated with anti-calcification (or
`anti-mineralisation) agents. Many techniques have been
`used to try and eliminate the use of glutaraldehyde as the
`tissue preservative. None of these has yet had commercial
`success. Modern porcine bioprostheses are no longer fixed
`under high pressure, which was meant to give the prosthesis
`a certain ‘‘shape’’ to make them more like the native valve. In
`these porcine valves, a backpressure of 80 mm Hg was used
`
`www.jclinpath.com
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`EARLY COMPLICATIONS
`
`A.
`1.
`
`2.
`
`0–2 days
`Mortality
`(a)
`Single valve procedure: 2–10%
`(b)
`Multiple valves: 5–10%
`
`Morbidity
`(a)
`Acute myocardial injury
`(b)
`Post operative "pump" failure (no myocardial necrosis)
`(c)
`Injury to bundle of His or bundle branch
`(d)
`Injury to left circumflex coronary artery
`(e)
`LV rupture/aneurysm
`
`B.
`1.
`2.
`3.
`5.
`
`2–30 days
`Thrombosis
`Infection
`Prosthesis disproportion
`Prosthesis dehiscence/perivalvular leak
`
`LATE COMPLICATIONS
`
`C. Greater than 1 month
`Haematological
`1.
`(a)
`Thrombosis
`(b)
`Emboli
`(c)
`Haemorrhage
`
`2.
`
`Infection
`(a)
`Annular abscess (mechanical)
`(b)
`Infective endocarditis (bioprosthesis)
`
`D.
`
`Years
`(a)
`Bioprosthesis
`(i)
`Tissue degeneration
`(ii)
`Cusp calcification
`(iii)
`Cusp tears
`Mechanical
`(i)
`Fracture of prosthesis components
`
`(b)
`
`Figure 12 Early and late postoperative complications of prosthetic
`heart valves. LV, left ventricle.
`
`during the glutaraldehyde treatment, but in contrast some
`contemporary valves are fixed with a zero pressure gradient
`across the valve or stress free fixation.4 This is meant to
`eliminate stretching of the cusps and flattening of the cuspal
`connective tissue—that is, removal of the ‘‘crimp’’ from the
`porcine tissues.
`
`Pannus
`Pannus, or the host tissue reaction to devices, is usually
`relatively mild and occurs at the host–fabric or host–tissue
`interfaces. From there, this host tissue reaction, if significant,
`can progress on to the sewing cuff (figs 3, 7, 9) and up to the
`
`Table 2 Worldwide use of prosthetic heart valves
`
`Estimated numbers
`
`Prosthesis
`
`1994*
`
`2003À
`
`Total
`Mechanical
`Ball in cage
`Tilting disc
`Bileaflet
`Bioprosthesis
`Porcine
`Pericardial
`Allograft
`Native valve repair
`
`173 900
`121 000 (70%)
`4900
`22 000
`95 200
`52 900 (30%)
`31 000
`18 700
`3200
`
`370 700
`192 764 (52%)
`
`114 917 (31%)
`
`Approximately 10–20%
`
`*From Schoen2; ÀMedtronic Inc (valve division), personal communication,
`2004.
`
`BHV interface between the biological and non-biological
`materials. Pannus can extend further into the biological
`components,
`leading to their stiffening and progressive
`stenosis and dysfunction.12–17 In MHVs, this pannus may
`grow over the prosthesis ring and predispose to thrombosis.5
`Today, of the more than 370 000 PHVs implanted annually
`worldwide, just over half are mechanical, and of these, most
`are of the bileaflet tilting disc type, whereas approximately
`one third are tissue valves, with porcine aortic valve
`bioprosthesis being the most common (table 2). An increas-
`ing number of valves, especially mitral valves, are ‘‘repaired’’
`(15–20%).
`
`Results of heart valve replacement
`Figure 12 summarises the postoperative complications of
`prosthetic heart valve replacement. The mortality associated
`with heart valve replacement is variable and depends among
`others on the expertise of the surgical team, whether the
`procedure is being performed for the first or second time, and
`if it is a single or multi valve replacement. The average
`mortality rate ranges from 3.5% for a single valve, first time
`replacement to about 10% or more for a double valve or
`second time replacement. As the number of
`times the
`procedure is repeated or as the cross clamp (ischaemic time)
`time increases, so does the operative morbidity and mortality.
`In addition to the status of the native valve itself, the status
`of the myocardium is extremely important for the patient’s
`prognosis. A large number of early deaths are related to poor
`myocardial function, the result of longstanding valvular
`disease, and to long delays in surgery. This may be
`exaggerated by perioperative myocardial damage.18 In con-
`trast, late death (30 days or more after surgery) is more often
`related to the prosthesis or further myocardial degeneration
`leading
`to
`congestive heart
`failure
`or
`arrhythmias.
`Interestingly, about 40% of patients with PHVs who die
`suddenly, die of valve related causes.19
`Postmortem studies on explanted heart valves show a
`somewhat higher rate of valve related pathology than was
`clinically suspected. Substitute valves have relatively poor
`function in comparison to native valves; most have some
`degree of obstruction and incompetence related to the stent
`and the occluder. The occluder is reportedly built in to allow
`the surfaces to be ‘‘washed’’ during diastole and therefore
`avoid thrombosis. Up to 10 years after surgery, prosthesis
`associated complications are the cause of death in 50–60% of
`patients who have prosthetic heart valves.2 5 The overall rate
`at 11 years
`is
`similar
`for mechanical and biological
`prostheses.7 Common prosthesis associated complications
`may be classified as: (1) thrombosis, thromboembolism,
`and associated problems; (2) infection, annular or on the
`biological tissues; and (3) structural dysfunction and non-
`structural dysfunction.
`
`‘‘Interestingly, about 40% of patients with prosthetic heart
`valves who die suddenly, die of valve related causes’’
`
`Thrombosis is much more common in patients with MHVs
`than in those with BHVs. Patients who have MHVs have to be
`maintained on lifelong anticoagulant treatment and their
`coagulation status evaluated on a regular basis. Thrombosis
`probably starts in the low flow areas of the prosthesis,
`especially the hinge areas. The thrombus spreads until the
`occluder or hemileaflets are progressively restricted in their
`movement, leading to prosthesis dysfunction and increasing
`stenosis.20 Thrombus can form in bioprostheses also, but this
`is relatively rare.17 It may occasionally be seen in the smallest
`of the three cusps (generally posteriorly placed) of some
`porcine bioprosthesis.
`
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`
`Figure 13 A Carpentier-Edwards annuloplasty ring. This D shaped ring
`has a hard metal core.
`
`Figure 14 A soft Edwards-Physio annuloplasty ring. It has a soft,
`synthetic core covered with synthetic fabric.
`
`Infection
`Infection of the PHV may be annular or may involve the
`surface of the biological components. In MHVs, the infection
`generally involves the annulus and may lead to extension of
`thrombus over the prosthesis. Annular infection can spread
`and lead to further complications. In BHVs, the infection
`usually occurs on the tissue components, although it may
`also occur around the annulus. Infection of the tissues may
`lead to their destruction and to further prosthesis dysfunc-
`tion. The rate of infection of mechanical and biological PHVs
`is similar.7
`
`Dysfunction
`Any of the changes listed above can lead to prosthesis
`dysfunction. Other reasons for prosthesis dysfunction may be
`host related, and these include tissue overgrowth (also
`known as pannus), and material degeneration. Further
`details about these modes of dysfunction can be found in
`larger reviews on bioprosthesis dysfunction.2 12 13 17 Structural
`dysfunction in MHVs is rare today. In the past, fractures of
`tilting disc valves have been reported, especially involving the
`Bjork-Shiley convexo–concave valves.14 21 Disc or housing
`fractures have been reported in the carbon components of
`bileaflet valves.22 Non-structural dysfunction is probably a
`result of an abnormal
`tissue–prosthesis reaction. These
`includes paravalvular leaks, suture failure, and suture line
`dehiscence.
`
`Detailed examination of prostheses
`At times, mechanical heart valve prostheses need to be
`examined in greater detail, usually as part of an ongoing
`study, or if a new prosthesis is being designed and tested in
`animals. In human explants, prostheses are examined further
`if they show evidence of premature dysfunction, disruption,
`or premature failure of parts of the mechanical components,
`
`Figure 15 x Ray of an aortic arch and descending segment with a stent
`in place (D). Two of the stent struts show fractured segments (arrow).
`
`such as a fracture of a hemileaflet or escape of a leaflet. This
`examination is best performed by dissection microscopic
`examination of the hinge areas and the surfaces. It may be
`necessary to remove all host tissues from the sewing cuff and
`clean the prosthesis with sodium hydroxide (10% sodium
`hydroxide solution). Scanning electron microscopy of frac-
`tured components may help define modes of failure.
`Detailed examination of prostheses (valves or stents) may
`be performed for follow up studies or for the evaluation of
`new devices. These studies can include non-destructive
`examination of the device by small specimen computerised
`tomography, or embedding the e