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Histopathology 2008 DOI: 10.1111/j.1365-2559.2008.02993.

REVIEW

National guidelines for adult autopsy cardiac dissection and


diagnosis are they achievable? A personal view
S K Suvarna
Department of Histopathology, Sheffield Teaching Hospitals, Sheffield, UK

Suvarna S K
(2008) Histopathology

National guidelines for adult autopsy cardiac dissection and diagnosis are they achievable?
A personal view
Adult autopsy cardiac pathology has been previously a
quiet backwater of ischaemic heart disease and the
occasional cardiomyopathy. This has changed to an
increasingly tense area, following recent genetic discoveries and some medicolegal cases. All autopsy
pathologists should consider their dissection protocols

and check that they are able to deliver the increasingly


detailed information that clinicians, geneticists and
families require. This text has suggestions about the
practical realities of cardiac dissection, cardiac histology and the need for other tests alongside illustrations
aimed to assist case consideration.

Keywords: autopsy, cardiomyopathy, heart, sudden adult death syndrome


Abbreviations: Ao, aorta; AoV, aortic valve; AV, atrioventricular; AVN, atrioventricular node; BB, bundle
branches; CxA, circumflex; Diag, diagonal; EVG, elasticaVan Gieson; GMC, General Medical Council; GUCH, grown
up congenital heart disease; H&E, haematoxylin and eosin; HisB, His bundle; IVC, inferior vena cava; LA, left
atrium; LAD, left anterior descending; LIMA, left internal mammary artery; LMS, left main stem; LV, left ventricle;
LVOT, left ventricle outflow tract; MV, mitral valve; OM, obtuse marginal; PA, pulmonary artery; PAS, periodic
acid-Schiff; PIVD, posterior interventricular descending; PV, pulmonary valve; RA, right atrium; RCA, right
coronary artery; RV, right ventricle; RVOT, right ventricular outflow tract; SADS, sudden adult death syndrome;
SAN, sinoatrial node; SVC, superior vena cava; TV, tricuspid valve

Introduction
The impetus for review of autopsy methodology for
cardiac diagnosis have been gathering for some time.
Starting from aspects of Alder-Hey and Bristol, through
considerations of Coronial service review (now shelved
yet again) to the phased implementation of the Human
Tissue Act (2004), with its requirement for licensing of
autopsy-related activities from 1 September 2006,
autopsy practice has been under increasingly intense
scrutiny. Other drivers include the criticism of some
pathologists autopsy practice in various National
Address for correspondence: S K Suvarna, Department of
Histopathology, Northern General Hospital, Sheffield Teaching
Hospitals, Herries Road, Sheffield S5 7AU, UK.
e-mail: s.k.suvarna@shef.ac.uk
 2008 The Author. Journal compilation  2008 Blackwell Publishing Limited.

Confidential Enquiry into Patient Outcome and Death


and Confidential Enquiry into Maternal and Child
Health reports,1,2 clinical governance requirements to
audit certain categories of deaths, and National Service
Framework cardiac disease framework documents3
setting treatment and outcome standards in cardiac
disorders known to cause sudden death. This has been
matched by fast-paced technological developments in
cardiology,4 steady unravelling of the molecular
pathology of cardiac disease5 and rising interest from
national bodies68 that help families in inherited
cardiac disease.
While the Human Tissue Act (2004) lists activities
relating to the use of human tissue from the deceased
which require relatives consent,9 the performance of
coronial autopsies the bulk of UK pathologists

S K Suvarna

workload falls outside its remit. In one General


Medical Council (GMC) case this year a pathologist was
severely criticised for not retaining the heart and
obtaining specialist cardiac opinion.10 In theory, retention of tissues and organs from a coronial autopsy
without relatives consent is permissible under Coroners Rule 9, to confirm the cause of death.11 In
practice, Coroners vary widely as to how they interpret
that rule, in many instances leaving it up to the family
to decide. Pathologists are thus caught in the middle12
and must be confident in making a case to retain, and
possibly refer, heart tissues in order to provide as
accurate a cause of death as possible.
All in all, it is time to review the objectives and the
methods pathologists employ with autopsy practice and
interpretation of heart disease. All autopsy practitioners (qualified and in training) should be able to
perform a sound review of the heart and its connecting
vasculature akin to the minimum dataset for a cancer
report. Previous work has covered some of the current
needs, in the form of published guidance.1318 This
means that, given the above drivers, any substandard
or weak case analysis may not be tolerated medicolegally in the future.
Certainly, knowledge of normal cardiac architecture
and function is mandatory, and if this is weak then
corrective continuing professional development activity
is needed. There is a balance to be derived between the
majority of autopsy cardiac cases recognized to be
routine and those requiring greater consideration, as
set out below. Thus, one might argue that many causes
of ischaemic heart disease can be assessed signed
off without written recording of every detail of the
dissection as set out below. However, it is no longer
acceptable to simply go through only the basic
motions of cardiac dissection. Some considered
thought is required on every case. This document has
therefore been produced to aid processing of the
routine case, and yet to prompt thoughts beyond just
the macroscopic autopsy and to facilitate later case
analysis.

Preparation for the autopsy


Before putting knife-to-skin, knowledge of the patients
medical history and interventions may be directly
relevant to the dissection and interpretation. In many
cases this history is lacking. However, this cannot be
used as an argument to defend weak practice. Interaction with the general practitioner, family and
witnesses is advised, particularly in cases of unexplained sudden death. Communication with relevant
cardiac centres and access to clinical records may also

be needed. Of particular importance is good information pertaining to sudden deaths, and this should be
derived from witness accounts if possible. Since many
cases are derived from the Coroner Procurator Fiscal,
their assistance may be vital in securing data on the
pathologists behalf.
Certainly, the consideration of consent and Coronial
medicolegal instructions is essential before the autopsy,
and critical if considering retaining tissues. Specialist
investigation preservatives and culture transport media, for the purposes of electron microscopy, microbiology and DNA extraction, should be considered prior to
the commencement of the dissection in order to
optimize sampling, and these should always be available in a mortuary.
Digital photography is a quick and cheap adjunct to
autopsy diagnosis, and camera facilities should be
available in any mortuary. A digital image of mid-low
ventricular transverse section s and other views of the
heart are very helpful as a record, and for referral.
Indeed, they may obviate the need for retention of the
whole organ. Tissue retention of the whole organ is
understood to be particularly problematic in some parts
of the UK, reflecting individual Coronial jurisdictions.
However, in sudden cardiac death organ retention and
referral should be regarded as the gold standard, with
many cardiac pathologists being prepared to examine,
block and turn around cases with a few days. Families
can be reassured that the bulk (usually more than 90%
of the cardiac tissues) can be reunited with the body in
such circumstances.
Digital photography is not mandatory for all cases.
However, in some cases the images may be a vital part
of autopsy record and comprise part of the text report
as illustrations. It is advisable to consider acquire
appropriate consent for consent autopsies and to
indicate to the Coroner that images have been taken
in medicolegal cases. There is GMC guidance on this
matter.19 The author has not had any problems with
regard to images being recorded and published (as in
this paper) provided that the case image is anonymous
and the reasons for image capture are made clear at the
time to interested parties.

Referral pathways
Some cases can be handled by all autopsy practitioners,
whereas others may benefit from wider discussion
and or referral. Most ischaemic and valvular heart
diseases can probably be dealt with by all qualified
autopsy pathologists. However, trainees without the
MRCPath (or equivalent) must have all cases checked,
no matter what their seniority.

 2008 The Author. Journal compilation  2008 Blackwell Publishing Ltd, Histopathology

National guidelines for adult autopsy cardiac dissection

Table 1. Causes of sudden cardiac death

Table 1. (Continued)

Coronary artery disease and ischaemic heart disease


Atherosclerosis

No morphological abnormalities (SADS)


Functional conduction system abnormalities (long QT
syndrome, Brugada syndrome)

Structural congenital malformation (including


anomalous origin)

Catecholaminergic polymorphic ventricular tachycardia

Kawasakis disease

Idiopathic ventricular fibrillation

Myocardial bridging

Blunt chest trauma (commotio cordis)

Coronary artery dissection


Aortitis and secondary atherosclerosis
Embolism into coronary arteries
Fibromuscular dysplasia of intramyocardial artery
Coronary artery spasm (regional infarction in
absence of coronary lesion)
Valve disease
Aortic stenosis
Mitral valve prolapse
Infective endocarditis
Myocardial disease
Myocarditis (including cardiac sarcoidosis)
Cardiomyopathies
Left ventricular hypertrophy and hypertension
Idiopathic myocardial fibrosis
Amyloidosis
Cardiac tumour primary (myxoma) or metastatic
Structural conduction system abnormalities
Absence of atrial portion of atrioventricular node
Bundle of His damage
Nodal mesothelioma
Atrioventricular nodal artery stenosis
Anomalous conduction pathways
(e.g. Woolf-Parkinson-White syndrome)
(NB diagnosis relies on ECG evidence in life or positive
family history. Serial sectioning of conduction system
for routine diagnosis is unnecessary)
Drug toxicity
Cocaine
Amphetamine and ecstasy
Solvent abuse
Marijuana6
Antidepressants and antipsychotics7,8

Complex cardiac disease, such as primary congenital


heart disease, grown up congenital heart disease (GUCH)
or those cases with complex medical interventions

Other clinical scenarios in which sudden cardiac death


may occur
Sudden death in athletes
SUDEP
Congenital heart disease (including GUCH)
Following cardiac surgery interventions
Cardiac involvement in systemic disease (connective
tissue disorders, sickle cell disease, metabolic and
endocrine heart disease)
Disseminated malignancy

(electrophysiological surgery, mechanical assist devices,


etc.) could be performed by general pathologists, but
only provided they feel confident on these problems.
However, they are better placed in the hands of those
with cardiac interest or specialist cardiac pathologists.
It is emphasized that sudden death, particularly in
young individuals, requires very careful consideration,
tissue retention and a wide range of investigations in
order to maximize the chance of obtaining a diagnosis.
A wide range of scenarios is possible, as highlighted in
the College of Pathologists Cardiac Pathology Autopsy
Scenario, no. 113 (Table 1). Discussion of the case with
the family is often beneficial, particularly if there is a
positive family history, and it is advisable to liase with
regional cardiac pathologists.
Pathologists facing difficult cardiac autopsies, which
they feel challenge their expertise, are advised not to
start such cases and are recommended to seek out
request the Coroner to contact specialist cardiac pathologists, possibly through a formal nationwide Cardiac
Pathology Network.20 The Coronial system is aware of
the realities of complex heart cases and it should not be a
problem for case triage and referral. This may occur at
different levels, depending on the issues being considered and the skills of the individual pathologist.
The Cardiac Pathology Network is being set up
within the UK, interacting with the Royal College of
Pathologists and British Association of Cardiovascular
Pathologists. A national database is being established
for pathologists to register cases of sudden cardiac
death. The Network will also foster education on

 2008 The Author. Journal compilation  2008 Blackwell Publishing Ltd, Histopathology

S K Suvarna

cardiac pathology for pathologists and will establish


links with the Department of Health, the Coroners
Society and the British Heart Foundation.

The autopsy
in situ ma cr o sc op ic r e vi e w
The heart should initially be examined in situ, having
exposed opened the pericardium by removal of the
anterior chest wall. At this point, one should sequentially examine the connections of the major arteries
and the gross external architecture of the heart and
the pericardium. This should be accomplished before
removal of the heart from adjoining structures. Any
grafts [e.g. left internal mammary artery (LIMA), vein
grafts] and electrical pacemaker connections should be
identified and preserved intact with the cardiac tissue.
Any effusions and or blood collections should be
recorded in terms of volume and character.
Open the pulmonary artery (PA) about 20 mm
above the valve and follow with fingertip palpation
within the proximal internal PA trunk (to avoid
disrupting and missing proximal pulmonary emboli).
Then transect the aorta (Ao) and PA. Transect the
superior vena cava (SVC) at least 10 mm above the
atrium and SVC interface, preserving the sinoatrial
node (SAN; Figure 1). One should now lift the apex
of the heart upwards in a cranial direction, allowing
transection of the four pulmonary veins and the
inferior vena cava (IVC), making sure that the posterior
atrial wall and septum are kept intact with the heart.
The heart should again be considered from anterior
and posterior aspect to assess whether the arrangement
of the atria and ventricles is normal. The right and left
atria have a triangular and rectangular appendage
architecture, respectively. The right ventricle should be
of palpably less thickness than the left, but both
ventricles should be more precisely and objectively
measured, as below. At this point it is possible to open
the back of the right atrium [RA; along the posterior
wall of the septum in a line from the IVC to the SVC;
and 10 mm parallel to the posterior wall septum
interface on the left atrium (LA) after opening across
the LA roof between the pulmonary veins] in order to
inspect the superior aspect of the tricuspid valve (TV)
and mitral valve (MV), but do not cut into across the
valve rings (Figure 2).

The coronary arteries


The prime object is to consider the course and
architecture of the coronary arteries. Any abnormali-

Figure 1. A referral fixed heart showing the crista of the right


atrium (RA) and the superior vena cava (SVC). The position of the
sinoatrial node (SAN) is indicated (*) along with black lines indicating
where cuts should take place to excise this tissue (black lines).
The piece of tissue should be sectioned along the line of blood flow
(i.e. longitudinally). For histology see Figure 12.

MV

TV

Figure 2. Opened atrial chambers showing the intact normal


tricuspid valve (TV) and trabeculated auricle; and mitral valve (MV)
and left appendage from above.

ties should be recorded, and ideally photographed


(Figure 3). It is recognized that some coronary artery
variations are particularly associated with sudden
death.21

 2008 The Author. Journal compilation  2008 Blackwell Publishing Ltd, Histopathology

National guidelines for adult autopsy cardiac dissection

PA

TV

Figure 3. A previously dissected and fixed heart showing the right


ventricle (RV) and pulmonary artery (PA) with an anomalous left
main stem (LMS) origin (arrow) from the PA in young female case of
sudden death.

The internal aspect of the coronary arteries should


be assessed by stepwise transverse slices at no more
than 5-mm intervals (Figure 4). All of the coronaries
should be assessed, and this means not just the easily
discerned large branches. It is generally agreed that
cutting coronary arteries longitudinally can disrupt
thrombi or emboli and make assessment of stenosis
difficult. A sharp scalpel blade is essential.
The coronary artery procedure will be more difficult
with heavily calcified vessels. In such circumstance the
solutions include, first, using scissors for the transverse
cut. Although quick, this will distort (and possibly
destroy) the inner plaque and any potential thrombus.
However, it is a realistic solution in many cases, and
yet must be balanced against the ideal of calcified
coronaries being dissected from the heart en bloc,
decalcified overnight and then serially sectioned as
standard. The tissues may thus be returned to the body
the next day. These options should be considered and
discussed with the Coroner family where relevant, but
usually the decalcification cut return next day protocol should not create any tissue retention issues.
In practice, inspection and cutting are nearly simultaneous, and a standard system will reduce missed
areas of tissue. I recommend starting the transverse
cuts in the middle of the left anterior descending (LAD),
sweeping downwards towards the apex, then upwards
towards the left main stem (LMS) orifice. Thereafter,
identify and examine the circumflex (CxA) and local
branches [diagonal (Diag) obtuse marginal (OM)

Figure 4. Regular slices are made along the coronary arteries at


5-mm intervals. The left anterior descending (LAD; arrowed) is
running from the scalpel blade position off towards the 3 oclock
boundary, with the Diag running from the mid section of the LAD
towards 1 oclock.

1 OM2]. Finally, the right coronary artery (RCA) in


the sulcus between the atrial appendage and right
ventricle should be examined with similar cuts around
the right side of the heart towards along the acute
marginal and posterior interventricular descending
(PIVD).
It is possible to remove small segments of artery, if
the case is to be demonstrated to clinicians or in
examination scenarios. However, if there is a possibility
that subsequent second autopsy examination may
follow, then no tissue should be separated from the
heart unless it is to be reserved for histology. If areas of
interest are left in situ, it is always possible to mark
areas of interest with small sutures clips.
Stenosis is probably best measured by an estimate of
lumen area total coronary area. This is to a degree
subjective, but stenosis >70% correlates reasonably
well with the probability of sudden ischaemic cardiac death.18,22,23 One should recognize that milder
stenoses do not exclude ischaemic pathology taken in
isolation, since they may have produced local thrombosis and sudden high-grade artery obstruction, with
fatal consequences. Stenoses may alternatively be
quantified as diameter of lumen at the point of
maximum disease, and lumens of 1 mm are associated with the risk of cardiac arrest.18,22 In some
complex cases it may be best to dissect free the
coronary arteries intact, decalcify and serially section
at 5-mm intervals, thereby providing a better overview
(Figure 5).
Coronary metal stents are increasingly common,
and cannot be dissected with scalpel or scissors. If the
stent requires investigation of the lumen then this
should be removed en bloc for resin embedding and

 2008 The Author. Journal compilation  2008 Blackwell Publishing Ltd, Histopathology

S K Suvarna

CXA
OMI
LAD

RCA

PIVD

Figure 5. The major branches of the coronary tree have been


removed, decalcified for 48 h and then sectioned. This allows clear
assessment of vessels and overview of the pattern of atheroma. The
arteries are marked and run from the left side of the image in
sequential fashion in serial slices. The maximal stenosis (*) is seen in
the left anterior descending (LAD) territory.

Figure 7. Heart radiology showing position of stented vessels.

tissue). However, this creates a whole host of artefacts


and could be criticised. In cases where legal consideration of the device is paramount, then resin embedding
is advised. Plain X-ray techniques are useful, particularly with cases where the stent position is not known
or where there are overlapping or branching stents
(Figure 7).

The myocardium

Figure 6. A resin-embedded artery showing well-deployed wire


struts deforming the artery wall and creating a wide lumen. This is
a good technical result from angioplasty and stenting.

subsequent specialist cutting microtomes (Figure 6).


I am fortunate to have this available locally and so
this is my personal experience, but in reality it may
taken up to 1 month for sections to be available.
Otherwise, up downstream artery analysis usually
suffices, with the proviso that gentle syringe injection
of water along the stented vessel will identify blockage free flow. Some advocate, in the absence of resin
embedding and specialist sections,24 that it is reasonably informative and practical to peel the coronary
wall around off the stent, visually inspect and gently
retrieve in-stent material for additional histological
evaluation (whether it is thrombus or restenotic

Immediately after the coronary examination, unless


there are other considerations such as congenital heart
disease, three transverse slices of ventricular tissues
(approximately 1015 mm thick) should then be taken
starting at the apex and finishing close to the base of
the papillary muscles, making sure that the TV and MV
tissue is not damaged. Areas of infarction and scarring
may be evident immediately, and mid-transverse
chamber views may be photographed, giving a
clear indication of ventricular chamber architecture
(Figure 8).
If there is any suspicion data to suggest a cardiac
anomaly malformation, I recommend that the three
transverse slices are not taken initially, but rather one
should open the myocardium along the line of blood
flow to inspect the heart cautiously. Later, if desired,
superglue will allow re-sealing of the myocardium and
permit one to perform the transverse slices.
If there is suspected pathology to the TV or MV then
direct inspection of the ventricular aspect is possible
at this point without further cuts. However, usually
following the transverse cuts, the RA and right
ventricle (RV) may then be fully opened continuing
along the posterior wall of the RA into the RV just next
to the septum, approximately 10 mm to the side of the

 2008 The Author. Journal compilation  2008 Blackwell Publishing Ltd, Histopathology

National guidelines for adult autopsy cardiac dissection

Figure 8. The three transverse slices are examined with the right
side myocardium on the left hand aspect, akin to computed
tomography style with right and left side indicated. The overall
architecture of the chambers is apparent.

Figure 10. The right ventricular outflow tract (RVOT) is opened and
should be measured in thickness. This case had a background
pulmonary disorder with some thickening of the RVOT due to
pulmonary hypertension. Attention should always be paid to the
presence of fibrosis or fatty tissue.

Figure 9. The opened right atrium (RA) and right ventricle (RV) are
seen with the auricle being easily inspected (*). There is no need to
further incise the RA appendage. The fossa ovalis is closed (arrow).

PIVD. This posterior approach allows direct inspection


of the complete TV, atrial auricular and ventricular
tissues (Figure 9). At this point, inspect, but do not
make any further slice into the auricle.
The cut should then be continued round onto the
front of the RV and upwards through the right
ventricular outflow tract (RVOT) and pulmonary valve
(PV) (Figure 10). The circumferences of the TV, PV and
thickness of the RVOT should be considered recorded,
along with other comments with regard to fatty
infiltration25 (Figure 11), thrombus, vegetation, etc.
The left side chambers are similarly inspected, with
the cut continuing from the posterior low LA into the
left ventricle (LV) 10 mm parallel to the PIVD. This
allows direct inspection of all the left-sided chambers
and auricle, again without cutting into the auricle
(Figure 12). It is possible to lift the MV at this point and
inspect the aortic valve (AoV; Figure 13). However, the

Figure 11. The free wall of the right ventricle (RV) may have a
variable thickness of fatty wall tissue (top image), often underappreciated until histology. The histology (bottom) shows the normal
fatty wall structure from the epicardium (E) to the chamber lumen (*).

incision is now extended onto the anterior aspect of the


LV to run along the edge of the anterior free wall,
parallel to the LAD, until just under the anterior leaflet
of the MV without damaging this valve. Thereafter,
scissors are usually required to produce a partial righthand turn, cutting between the base of the left auricle
and immediately behind the LMS, thereby opening into
the left ventricle outflow tract (LVOT) and Ao, through
the AoV (Figure 14). The position of the ostia and
their patency should be assessed. The MV AoV circumferences and LVOT thickness should be considered recorded. It is advisable to avoid the lateral
approach to the left ventricular tissues and or slicing

 2008 The Author. Journal compilation  2008 Blackwell Publishing Ltd, Histopathology

S K Suvarna

LA
RA

LMS
auricle

RV
LV
LAD

Figure 12. The left atrium (LA) and left ventricle (LV) can be seen
from the posterior aspect, along with part of the right side tissues.
It is not necessary to further incise the LA auricle, as the content
can be directly viewed.

MV

Figure 13. The mitral valve (MV) can be lifted gently using forceps to
inspect the aortic valve (AoV) inflow (arrow). The superior aspect can
be seen from the transected aorta (Ao). Given the significance of
pathology at this position, it is important to consider the state of the
valve before any further cut is made.

into the aortic root through the MV, as later consideration demonstration of pathology is more difficult.
Photography of the chambers and valves is ideal at this
point, and consideration of atrial and ventricular septal
defects should occur at this juncture.
Once the heart has been fully opened in this fashion
it is possible to weigh the tissues, with subsequent
cross-comparison against standard charts for body
mass and sex.14,17 It should be noted (with regard to
referred cases) that fixation may increase heart weight
by up to 5%. It is also possible to inspect closely the
valves and to record ring circumferences, if relevant.
If there is fibrosis, distortion, calcification or other
pathology then this should be defined.
When considering global ventricular architecture it
has been suggested that measurement of ventricular

CXA

Figure 14. The left ventricular outflow tract (LVOT) and aortic valve
(AoV) are best examined after opening the heart from the front. Note
the arteries run as indicated in the image (red lines), and the cut
(black lines) is best made with scissors running upwards and between
the left atrium (LA) appendage and behind the pulmonary artery
(PA). Note, care is required not to damage the mitral valve (MV) as
one begins to make the turn of the cut towards the aorta (Ao).

wall thickness is a useful tool to assess cardiac


hypertrophy and chamber overload. Given that the
wall of either ventricular chamber is not uniform and
since pathologists tend to choose rather arbitrary
points to measure wall thickness, one may have issues
with this protocol. Personally, I do not recommend this
as a solution and prefer to measure the RVOT and
LVOT 10 mm below the valves (although not stringent,
I have found it is less prone to variable recording).
One can also consider dissected ventricle weights,
but this should not be employed unless this is the very
final task and with clear acceptance that the heart will
be rendered fragmentary with this examination. It
should not be employed in cardiac pathology cases, if
review will take place. The original description was on
fixed tissue with all the fat stripped from the myocardial
parenchyma. A fresh tissue assessment is possible, but
one must remember that this once-only protocol does
not permit secondary examination of cardiac tissue.
Nevertheless, fresh tissue weights of the separated
ventricular parenchyma may be of particular value
when considering cardiac hypertrophy, although I
generally reserve this only for considering cardiac
remodelling in lung disease cases. In addition, for
consideration of cardiac hypertrophy failure, the
transverse chamber diameter for the right and left
ventricles may be of assistance in assessing the degree
of cardiac status.
From a pragmatic stance, there are a variety of
options available when assessing hypertrophy, and the
choices methodologies used should be made on an
individual case basis.14,26

 2008 The Author. Journal compilation  2008 Blackwell Publishing Ltd, Histopathology

National guidelines for adult autopsy cardiac dissection

Once the macroscopic detail of the coronary arteries


and myocardium has been considered, it is then
possible to serially slice all the tissues of the ventricles
and septum at 5- to 10-mm intervals in order to
exclude small focal lesions. These fine cuts should not
be performed if one is wishing to demonstrate the case
to other pathologists, or before photography has been
accomplished, as this significantly distorts myocardial
architecture.
Finally, it should be remembered that the appreciation of myocardial tissue phenomena may be more
apparent after fixation, and one should ideally perform
both fresh and fixed examination if such opportunity
exists.

Histopathology
t is s u e bl oc ks
Tissue blocks should be taken only from areas of
myocardial tissue of relevance, and it is essential to
record the site of sampling. The choices must reflect the
needs of the case and the underlying pathology, as well
as other factors such as tissue retention. The scenarios
are diverse, but can be considered in the following
schema, although it should be remembered that even
the most stringent blocking will sample only about
10% of the organ mass, leaving 90% for return to the
body if desired.
I have only occasionally used frozen section at
autopsy, mainly for unexpected cardiac pericardial
tumours or to consider a possible myocarditis, before
choosing how to sample a case. However, in practical
terms I do not recommend this as standard practice.

Routine histology stains


In general terms, routine haematoxylin and eosin
(H&E)-stained 4-lm sections are sufficient, although
the Massons trichrome is very useful in differentiating
myocytes from local interstitial parenchyma. Additional histochemistry should be available to examine
connective tissue and intracellular components of
myocardial parenchyma using periodic acid-Schiff
(PAS), diastase-resistant periodic acid-Schiff, elastica
Van Gieson (EVG)+ ) Alcian Blue, Congo (or Sirius)
Red at 10 lm, Perls, and Toluidine Blue (note: at least
one myocardial block should have all these stains
performed). Consideration of myocarditis can be enormously enhanced by staining for CD3+ and CD68+
cells using standard immunohistochemistry and scored
per mm2. Specifically for the valve and coronary
tissues, the use of an EVG (often combined with an

Alcian Blue) is important alongside the standard


H&E. The possibility of valve sepsis requires martius
scarlet blue, Gram, PAS, Grocott, Gimenez and occasional ZiehlNeelsen stains for full analysis.
Electron microscopy may have a role rarely in some
myopathic conditions and mitochondrial disease, and
may require a sample to be taken.

Histology in cases with a normal heart


(i.e. pathology elsewhere)
It may not be required to sample heart tissue for
histology or other test, unless an underlying occult
disorder is suspected (e.g. metabolic disorder myocarditis), or to prove the heart was normal. It is emphasized that cases without apparent cardiac pathology,
such as those where the pathology is clearly evident in
other systems, should still have the above careful
examination of the coronary artery system, myocardial
tissue, valves and overall architecture balanced against
the history. The possibility of microscopic disease must
be weighed up carefully before electing to take no heart
tissue for testing.

Histology for macroscopic cardiac pathology


In cases with primary secondary cardiac disease (most
commonly coronary artery disease and myocardial
ischaemia infarction) it may be sufficient to fully
examine the tissue macroscopically, record the degree
of vascular occlusion stenosis as a percentage, state
the site size of infarction and or areas of patchy
fibrosis. Phrases such as moderate atheroma or
patchy infarction are of little use without some
qualifier of size and location. Cases that may be subject
to later medicolegal review should ideally be photographed (Figure 15).
Well-defined myocardial ischaemic damage does not
automatically require histological sampling as part of
the autopsy analysis, unless there is an issue that
requires histological assessment (e.g. dating of infarction, exclusion of other myocardial disease). In such
cases sampling should evaluate both the pathological
and normal tissues. Thus, background coronary
artery maximal area of stenosis (with decalcification)
and damaged myocardial tissue will be taken often
sufficient with one to four blocks.
Cardiac involvement due to systemic disease
(Table 1) often requires thorough tissue sampling.
Although one to two blocks might suffice, wider
sampling may be governed by the nature of disorder and ante-mortem pathophysiology if clinical

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S K Suvarna

Figure 15. Infarcted posterior right ventricle (RV), left ventricle (LV)
and septum with rupture of wall by previously correctly placed
pacemaker wire. In this scenario the disease of transmural infarction
is the cause of the wire penetration and cardiac tamponade, and
not poor placement of the pacemaker electrode.

correlation is sought. Thus, metastatic disease to the


heart could require just one block, but consideration of
granulomatous myocarditis, drug toxicity, lysosomal
storage disorder, etc., may need up to six blocks, or the
specialist investigations as detailed below.
With valvular heart disease the choice of how much
tissue needs sampling will reflect the pathology present.
However, one to three blocks will normally be ample
(normal valve, abnormal valve myocardium). On
occasion, examination of all the valvular tissue and
hinge point histology may be required, with careful
excision, decalcification and histology. Microbiology
sampling, if considered, should always precede histology samples.
Assessment of the great vessels is occasionally
required and in most circumstances focused on the
aortic root and valve (rheumatoid disease, ankylosing
spondylitis, syphilis, infective endocarditis, etc.). Block
sampling along the line of blood flow and use of
connective tissue stains are very useful in these
circumstances.

Histology in sudden adult death syndrome


and the cardiomyopathies
Such deaths without clear macroscopic pathology are
complex and often require consideration of neuromuscular disorders, toxicology and genetic molecular
disorders, as well as the cardiac pathology issues.5,27,28
To do less might be considered as suboptimal and might
be challenged at a later date. Focusing solely on the
heart, such cases may require ideally referral of the

intact heart for specialist cardiac pathology review, and


it is wise to consider this even before starting the
autopsy. Indeed, it is unwise to proceed in a reckless
fashion in the hope that it will turn out to be coronary
artery disease!
The various cardiomyopathies are better recognized
and understood today. Given the impact for families
and the prognostic issues, it is stressed that some
review of potentially deadly disease occurs beyond the
statement that the case was a cardiomyopathy. More
is expected. Classic examples of hypertrophic cardiomyopathy, dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy (but including
its variants) should be well recognized, although rarer
examples will be found in texts.28 However, some
patients, and kindreds, are unique and a certain rigour
is needed for full assessment.
For these cases I would recommend the involvement
of cardiac pathologists or formal Cardiac Pathology
Network collaboration. Detailed family drug history
data2931 and results of prior investigations are likely to
be pertinent. It is certainly outside the scope of this
paper to cover this area in detail, but a working
knowledge of standard cardiomyopathy is needed if any
autopsy practice is to be undertaken. As with the
sudden adult death syndrome (SADS) cases, it is
expected that widespread mapped blocking, photography and the other related tests are considered
employed in order to maximize the data yield.
The standard autopsy examination should be augmented by photography, toxicology and thorough
histology sampling. Microbiology and DNA testing
may be relevant. The blocks (with the stains as detailed
above being regarded as mandatory) should always
reflect the consent Coroners realities, but ideally
should be standardized. One would be criticized for
suboptimal sampling of a gastric or lung cancer, so
why be different for an autopsied heart? My suggested usual pattern of blocking is indicated in parentheses, and it might be argued that some conformity
should occur (at least within the UK).
1 Coronary vessels (blocks 13 = LMS LAD, RCA
PIVD, CxA OM1).
2 Conduction system [blocks 4 + 5 = SAN, 6
12 = atrioventricular node (AVN) His bundle (HisB)
bundle branches (BB), 13 = septum TVs].
3 Atrial tissue (block 14 = right left).
4 LV RV septum lower (block 15).
5 RVOT (block 16).
6 LV anterior (block 17).
7 LV lateral (block 18).
8 LV apex (block 19).
9 LV posterior (block 20).

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National guidelines for adult autopsy cardiac dissection

11

10 Full mid-ventricular views of the right and left


ventricle septum, by the use of jumbo blocks (blocks
2123) these large blocks, obviate the need for
multiple small blocks and provide a good geography of
ventricular tissue.
It is prudent also to sample fresh spleen tissue (about
20 mm3), which should be sent fresh to the local
molecular cytogenetics unit immediately for DNA
extraction, etc. One should also reserve a small amount
of myocardial tissue for electron microscopy into
glutaraldehyde.
It is advised that one gathers all information possible
from the family doctor, hospital records and family. It is
recognized this may be a burden, but pathologists could
be putting themselves in jeopardy if they ignore the
chance to obtain vital data.

Conduction system histology


There are broadly two schools of thought on this issue:
those that do this technique regularly, and those who
do not perform the analysis, believing it is rarely of use.
Belonging to the first group, it has been rewarding to
find a cystic atrioventricular tumour, granulomatous
inflammation, calcification, lipo-atrophy of myocytes,
etc., when looking at conduction systems in the last
5 years. Although it is clear that the novel diagnosis
yield is low, at least one can feel confident with the
technique if regularly practised!
The cardiac conduction system cannot be discerned
macroscopically. There are a variety of texts on the
matter,16,17,32 although the illustrations in the late
Professor Davies 1985 atlas are very good.32 Consequently, wide blocking of tissues to capture areas of
relevance is required, and access to the whole heart is
needed. Once performed, the significant tissue sampling
means further macroscopic appreciation will be hampered unless photographs are taken beforehand.
The SAN is found at the apex of the crista of the right
auricle and SVC interface (Figure 1). This block of
tissue should be removed in an oblong piece of tissue
and longitudinal slices along the line of blood flow will
allow identification of the nodal tissue next to the SAN
artery (Figure 16). The tissue is composed of a rather
haphazard group of mid-sized myocytes with local
ganglion cells and very slight fibrosis.
The AVN is found at the apex of the triangle of Koch
(bounded by the superior limb of the coronary sinus,
membranous septum and superior edge of the TV
leaflet). This is best removed in a square piece and then
blocked in sequential stepwise slices right to left in a
longitudinal fashion (Figure 17). The AVN myocytes
show a similar histology to the SAN.

Figure 16. Sinoatrial node (SAN) histology showing the irregular


nodal tissue and artery (arrowed) adjacent (H&E).

AVN

Figure 17. The right atrium (RA) and right ventricle (RV) view
here allows identification of the triangle of Koch (green lines) and
the likely position of the atrioventricular node (AVN). The HisB and
bundle branches (BB) lie immediately below and deep to the AVN.
To examine these fully one needs to resect a square of tissue (black
lines) to encompass all the conduction system elements. The slices
taken in the short (superiorinferior) axis should incorporate the fatty
atrial parenchyma, the membranous septum and the top of the
muscular septum (lower right inset).

This process will also allow identification of the BBs,


HisB and AVN, as one progresses in blocks from left to
right (Figure 18). However, step sections through the

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S K Suvarna

Figure 18. The radiating bundle branches are seen in longitudinal


section here (arrowed). The Masson Trichrome is particularly useful
in highlighting cardiac myocytes within fibrous parenchyma.

paraffin blocks may be needed for full appreciation of


the tissues. The radiating fibres of the BBs can be best
appreciated by a transverse block of the high septum.
One should note that the BBs do not map to the
idealized scheme that most ECG texts suggest!

Cardiovascular devices
Temporary and permanent devices are increasingly
common in autopsy practice. Indeed, this is an evolving arena and what will be available in the next
510 years cannot be predicted. Ante-mortem data are
often paramount in appreciating issues before the
autopsy (e.g. defibrillator pacemakers, vi). However,
the examination should follow the above standard
protocols. Issues relating to medical and surgical
interventions with the complications successes provide feedback for clinicians, relatives and those with
medicolegal interest. Likewise, knowledge of the
cardiac intervention undertaken, for what primary
cardiac disease and whether any complications have
followed, is vital beforehand to maximize data retrieval
from autopsy examinations.

Figure 19. Attempted drainage of a loculated pericardial effusion


resulted in perforation of the heart by two drainage lines with a fatal
consequence.

bleeding or cardiac trauma, should have photography


(Figure 19).

Pacemakers
Cardiac pacemakers are increasingly frequent
(Figure 20) and almost all appear to be reliable. In a
personal review of more than 500 units removed after
death, I have found only one with a end of life battery
and none with abnormal program parameters. However, the pacemaker box should ideally be returned
to the local ECG cardiac pacemaker department for

Vascular access lines


These lines should be inspected at the time of autopsy
commencement externally, cut flush with the skin and
left so that internal positions can be checked during
subsequent organ dissection. Exclusion of thrombotic
change and sepsis around the site of introduction may
require microbiological sampling and occasionally
histology. Significant complications, such as massive

Figure 20. Twin lead permanent pacemaker insertion points to allow


more physiological heart pacing. Note the three transverse slices
have not been used in order to preserve the overall view of the
chambers.

 2008 The Author. Journal compilation  2008 Blackwell Publishing Ltd, Histopathology

National guidelines for adult autopsy cardiac dissection

assessment and case audit,33 with about 10 cm of the


lead still attached at least. The most likely scenario of
pathology for pacemakers is that of architectural
pathology. Exclusion of haemorrhage and sepsis (usually around the time of implantation battery change),
lead fracture, thrombosis around lines and infective
endocarditis at the lead insertion point s is required.
Ideally, the pacemaker box, its lead and electrode
should be examined, preferably in one piece with the
thoracic organ block.34 Suspected pathology may be
the driver for microbiology sampling, histology and or
photography as appropriate.
An implanted cardiac defibrillator must be switched
off before autopsy manipulation or removal, to avoid
the risk of accidental discharge during the autopsy
procedure.35 These devices are designed to generate
high-voltage shocks in response to cardiac dysrhythmias. The clinical notes and or family doctor should
have paperwork with regard to the pacemaker device
model. The local pacemaker clinic can then de-activate
the unit. Certainly, no pacemaker should ever be left in
the body, in order to avoid the risk of explosion at
cremation.

13

Figure 21. Suggested scheme to dissect the left atrium (LA) and left
ventricle (LV) in cases of mitral valve (MV) prosthesis, allowing
superior and inferior views to be examined. Solid lines are cuts on the
posterior face and broken line is continuation onto anterior aspect.

RA

Prosthetic valves
Valve replacement surgery broadly follows two patterns: those with tissue replacements (allograft or
xenograft) or artificial devices (usually metal).36
Although primary valve replacement failure can occur
due to technical issues, the primary pathologies include
local haemorrhage, infection, poor alignment, local
leak and tissue overgrowth across the valve (pannus).
It is not possible to open a prosthetic valve in a manner
similar to native valve tissue. Consequently, cardiac
dissection requires exploration of the valve from above,
as well as from below, to assess carefully the valve and
any pathology. Thus, opening an atrium along the
posterior aspect alongside the septum, then turning
90 to run the incision along around the atrial base
immediately above the atrioventricular (AV) groove to
approximately 50% of the atrial chamber is recommended for AV valve prostheses. The ventricles are
explored by opening the ventricular chambers from the
apex of the heart, running a cut upwards adjacent to
the ventricular septum posteriorly and then turning
90 towards the lateral aspect of the ventricular
chamber, allowing the ventricular chamber to be
displayed (Figure 21). For a PV or AoV prosthesis the
dissection may largely follow standard parameters, but
must allow for below above review of the prosthesis.
Finally, one relatively rare procedure for AV valves is
previous surgical valvuloplasty or partial prosthetic

RV

Figure 22. A partial ring tricuspid valve (TV) prosthetic valvuloplasty.

valvuloplasty (Figure 22). Standard exclusion of infective endocarditis and review of cardiac chamber
anatomy are most important in such cases.

Other devices
Developments are ongoing, and these are increasingly
common in cardiac tissues. Examples include, first,
septal closure devices, which broadly comprise two
umbrella platforms that are placed across the septal
leak (Figure 23). These should be inspected carefully as
the chambers are opened, with photography and

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S K Suvarna

Ischaemic heart disease intervention

Figure 23. Atrial septal device placed 5 years previously with good
effect, now sealed in by normal fibrous tissue and endocardial surface
tissues. The cruciate architecture can be made out below the surface.

Surgical and medical intervention for ischaemic heart


disease is still common, albeit with open surgical
therapy declining. In recent history, open surgical
coronary artery bypass grafting was the norm for
coronary artery disease. In recent decades, the LIMA
has been increasingly used. As above, ante-mortem
data are very important, particularly knowledge of the
number of grafts and the position to which they were
applied. This can save considerable time when faced
with a severely fibrotic pericardial tissue background.
Clearly, technical problems, such as sepsis, haemorrhage and infection, need documentation and possibly
photography. One is naturally primed to review the
grafted vessels, their attachments engraftments with
consideration of the background vasculature. This will
require ideally transversely cut vessels from the aortic
root along the graft, or along the internal mammary
artery graft. Some advocate using scissors to dissect
along the vessel, provided that the lower part of the
graft has been opened to identify any extruded thrombus foreign matter, although this is clearly less rigorous. Any re-stenosis should be evaluated, and scored as
for native arteries. In addition, histological sampling of
the downstream myocardium is advised to consider
ischaemia pathology extent and chronicity.
Finally, the native vessel disease and possible
obstruction thrombosis of the anastomoses must be
assessed. If these are heavily calcified then they should
be dissected whole, decalcified and considered by
histology, although tissue retention issues are pertinent
in deciding the dissection procedure employed (vs).
As discussed earlier, coronary stents are increasingly
common in autopsy practice, and are covered in the
above section on the coronary artery.

Figure 24. An aortic root replacement with aortic valve (AoV)


prosthesis. Note the insertion points of the two normal coronary
arteries.

Other complex cases

microbiology sampling as appropriate. Removal of the


tissues intact with the device is indicated if medicolegal
consideration is to be made. Second, patch or vascular
repairs, comprising Dacron-style materials, may be
seen in some cases (Figure 24). Attention to the suture
points is particularly important, to exclude infective
endocarditis. The standard advice regarding photography applies, alongside histology and microbiology
realities. Finally, ventricular assist devices (temporary
and permanent) are becoming increasingly used as a
bridge for those awaiting cardiac transplant. If encountered, then communication with the transplant centre
regarding the best approach is strongly advised.

Cases of cardiac transplantation and GUCH are


ideally considered by those with appropriate experience and expertise. If appropriate consent and
permissions exist, the heart should be removed intact,
washed through, fixed and dispatched for further
analysis. The tissues can be returned to the body on
many occasions, but this requires prompt access to
the Cardiac Pathology Network. The only alternative
is to extract, photograph and block the heart in the
manner of SADS cases. DNA extraction and other
tests may need to be undertaken. In general terms, I
always recommend speaking with the family directly
if tissue retention is stated to be an issue. One cannot be criticised later if (possibly with a cardiac

 2008 The Author. Journal compilation  2008 Blackwell Publishing Ltd, Histopathology

National guidelines for adult autopsy cardiac dissection

pathologist) one has attempted to advise the relatives


of the need to keep tissues, they have elected to
ignore such advice and their decision has hampered
reaching a coherent and accurate cause of death.

Conclusions
This paper set out to review the guidelines that should
govern safe, appropriate and helpful autopsy practice in
the UK. In short, they are achievable whether one is
working in a general or teaching hospital. I suspect
they could be applied outside the UK, nevertheless. The
paper is not an absolute set of rules, but rather strives
to develop dataset concepts in this complex field.
Ultimately, prosectors must chose for themselves what
the case requires. One must choose carefully which of
the above situations is applicable and how detached
the final text report needs to be. This will reflect the
individual case history and findings.
There are several useful resources that are recommended. These include information from the Royal
College Pathologists website,13 and the Association of
European Cardiovascular Pathologists SADS guidelines.15 General and autopsy texts on cardiovascular
disease are recommended,37,38 and access to some
specialist publications is also helpful. Time spent
beforehand considering local contacts is valuable, and
less stressful than if one is unprepared when a hot
case is present in the mortuary.
In writing an autopsy report it is important not to
forget the family. Inasmuch as pathologists need
background data, the families of the deceased need
feedback. Some may occur via clinicians, but one
should be prepared to meet relatives and to discuss explain the findings. These out-patient style
interviews often take up to 1 h and are draining, but,
in the authors opinion, are part of the job.
It is expected that this document will need updates
and re-working along with developments of medicine,
pathology, law, microbiology and genetics. However,
the days of a substandard cardiac autopsy are over, and
it is to be recommended that those active in this area
decide how they will deliver the modern cardiac
pathology for the nation.

References
1. http://www.ncepod.org.uk
2. http://www.cemach.org.uk
3. Department of Health Coronary Heart Disease National Service Framework. Chapter 8. Arrhythmias and sudden cardiac
death. 2005. Available at: http://www.dh.gov.uk/en/PolicyAnd
Guidance/HealthAndSocialCareTopics/CoronaryHeartDisease/
DH_4117048

15

4. Grech E. New developments in PCI intervention. ABC Intervent.


Cardiol. (in press).
5. Tester DJ, Ackerman MJ. The role of molecular autopsy in
unexplained sudden cardiac death. Curr. Opin. Cardiol. 2006; 21;
166172.
6. http://www.c-r-y.org.uk
7. http://www.sadsuk.org
8. http://www.cardiomyopathy.org
9. http://www.opsi.gov.uk/acts/acts2004/ukpga_20040030_en_
6sch1
10. http://www.rcpath.org/resources/pdf/g067additiontoautopsy
guidelinesnov07.pdf
11. http://www.england-legislation.hmso.gov.uk/si/si2005/20050420.
htm
12. Furness P. Coroners post-mortems: passion, problems,
perceptions and politics. Bull. R. Coll. Pathol. 2007; October;
6064.
13. The Royal College of Pathologists: Guidelines on Autopsy
Practice 2005. Scenario 1: Sudden death with likely cardiac
pathology. Available at: http://www.rcpath.org/resources/pdf/
AutopsyScenario1Jan05.pdf
14. Silver MM, Silver MD. Examination of the heart and cardiovascular specimens in surgical pathology. In Silver MD, Gottlieb AI,
Schoen FJ eds. Cardiovascular pathology, 3rd edn. New York:
Churchill Livingstone, 2001; 129.
15. Basso C, Burke M, Fornes P et al. Guidelines for autopsy
investigation of sudden cardiac death, Vichows Arch. Available
at: http://www.springerlink.com/content/1474562345g12014/
?p=10fbc48113974349a1c77de14da08334&pi=24
16. Sheppard M, Davies MJ. Cardiac examination and normal cardiac
anatomy. In Practical cardiovascular pathology. London: Arnold,
1998; 116.
17. Ludwig J. Handbook of autopsy practice. Totowa, NJ: Humana
Press, 2002; 2143, 554572.
18. Davies MJ. The investigation of sudden cardiac death. Histopathology 1999; 34; 9398.
19. http://www.gmc-uk.org/guidance/current/library/making_
audiovisual.asp
20. Burke M. Sudden cardiac death: a proposal for a Cardiac
Pathology Network. ACP News, Winter 2007.
21. Sheppard M, Davies MJ. Cardiac examination and normal cardiac
anatomy. In Practical cardiovascular pathology. London: Arnold,
1998; 4446.
22. Davies MJ. Coronary artery remodelling and the assessment
of stenosis by pathologists. Histopathology 1998; 33; 497
500.
23. Thomas AC, Knapman PA, Krikler DM, Davies MJ. Community
study of the causes of natural sudden death. BMJ 1988; 297;
14531456.
24. Virmani R, Burke A, Farb A, Atkinson JB. Pathology of vascular
interventions. In Cardiovascular pathology, 2nd edn. Philadelphia:
WB Sanders, 2007; 54108.
25. Tansey DK, Aly Z, Sheppard MN. Fat in the right ventricle of the
normal heart. Histopathology 2005; 46; 98104.
26. Sheppard M, Davies MJ. Cardiac hypertrophy, myocarditis and
cardiomyopathy. In Practical cardiovascular pathology. London:
Arnold, 1998; 103148.
27. Thiene G, Basso C, Corrado D. Cardiovascular causes of sudden
death. Cardiovascular pathology, 3rd edn. New York: Churchill
Livingstone, 2001; 326374.
28. Virmani R, Burke A, Farb A, Atkinson JB. Cardiomyopathy. In
Cardiovascular pathology, 2nd edn. Philadelphia: WB Sanders,
2007; 179230.

 2008 The Author. Journal compilation  2008 Blackwell Publishing Ltd, Histopathology

16

S K Suvarna

29. Lewis W, Silver MD. Adverse effects of drugs on the cardiovascular system. In Silver MD, Gottlieb AI, Schoen FJ eds. Cardiovascular pathology, 3rd edn. New York: Churchill Livingstone,
2001; 541561.
30. Glassman AH, Bigger TJ. Anti-psychotic drugs: prolonged QTc,
torsade de pointes and sudden death. Am. J. Psychiatry 2001;
158; 11741182.
31. Frassat D, Tabib A, Lachaux B et al. Hidden cardiac lesions and
psychotropic drugs as a possible cause of sudden death in
psychiatric patients: a report of 14 cases and review of the
literature. Can. J. Psychiatry 2004; 49; 100105.
32. Davies M. Colour atlas of cardiovascular pathology, Appendix 1.
New York: Harvey Miller, Oxford University Press, 1985; 170
173.
33. Suvarna SK, Start RD, Tayler DI. A prospective audit of
pacemaker function, implant lifetime and patient cause of death.
J. Clin. Pathol. 1999; 52; 677680.

34. Raasch F. Pacemaker autopsy. In Legal medicine annual. Boston:


Butterworth, 1977; ISSN: 0075-8590.
35. Medical Devices Agency Safety Notice 2002(35). Removal of
implantable cardioverter defibrillators (ICDs). 2002. Available
at: http://www.mhra.gov.uk/home/idcplg?IdcService=SS_GET_
PAGE&useSecondary=true&ssDocName=CON008731&ssTarget
NodeId=420
36. Schoen FJ. Approach to the analysis of cardiac valve prostheses
as surgical pathology and autopsy specimens. Cardiovasc. Pathol.
1995; 4; 241255.
37. Sheppard M, Davies MJ. Practical cardiovascular pathology.
London: Arnold, 1998.
38. Silver MD, Gottlieb AI, Schoen FJ (eds). Cardiovascular pathology,
3rd edn. New York: Churchill Livingstone, 2001.

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