Case 3 -
Senile Amyloid Involving Myocardium in Patient with Coronary Artery Disease and Bypass Surgery
Mary Sheppard, Royal Brompton Hospital, London, England
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75 year old male with routine bypass surgery as well as Mitral valve repair for floppy mitral valve. Prolonged bypass time 5 hours. Did not regain cardiac output and died on the operating table. At autopsy vein grafts to LAD,posterior descending coronary artery and obtuse marginal branch. No macroscopic evidence of acute or chronic myocardial infarction.
Case 3 - Slide 1
Coronary artery bypass surgery is still one of the most common procedures undertaken in cardiac
surgery. It is a procedure that is not been done as frequently as before due to the widespread use of
angioplasty and stent insertion for coronary artery disease over the last 30 years. Nowadays more and
more elderly patients are having cardiac bypass surgery particularly those who are obese and diabetic
with diffuse severe coronary artery disease so these have a higher mortality compared to the elective
Complications of CABG include pump failure post operatively with hypoperfusion and resulting multi
organ failure with cerebral, liver, mesenteric and renal failure. Bleeding is often a problem due to use
of ant platelet agents and coagulopathy due to prolonged bypass. There may also be acute myocardial
infarction which can occur with thrombosis within the native vessels and also in the grafts. Stroke may
occur after surgery due to thromboembolism
or poor perfusion. There may also be damage to the aorta leading to dissection. Arrhythmias may occur
during surgery which may lead to sudden death. Patients may also die suddenly post surgery with
pulmonary thromboembolism or lethal arrhythmia. Wound infection and septicaemia may occur especially in
diabetic patients.  Because the patients are elderly one must look out for other unexpected findings
which may result in death.
The clinical history in this case was that this patient died shortly after bypass surgery for
ischaemic heart disease. The surgery had gone well with a short bypass time and no problems during the
procedure. He died in the recovery room after suffering a cardiac arrest. He was aged 71 and it was an
elective procedure for worsening angina over past year prior to death. He had a previous history of
angina and hypertension. Our local medical examiner did not accept it and the autopsy was done as a
hospital post mortem.
The macroscopic findings showed a heavy heart weighing 600g which on sectioning showed circumferential
thickening of the left ventricle to 18mm thickness. There was no macroscopic evidence of infarction,
either acute or chronic. Examination of the graft shows a left internal mammery (LIMA) to the left
anterior descending coronary artery (LAD). The LIMA was intact with no thrombosis, dissection or
complications and the proximal and distal LAD showed no acute thrombosis or dissection. The proximal LAD
showed significant atheroma. The saphenous vein graft to the posterior descending coronary artery was
also intact with no thrombosis and while there was significant stenosis of the right coronary artery with
atheroma there were no complications of dissection, thrombosis or occlusion. The proximal anastomosis
site for the vein graft in the aorta and the distal anastomoses were also intact.
Routinely in coronary artery bypass surgery (CABG) blocks are taken from the proximal LIMA graft, the
anastomoses site and distal native vessel and anteroseptal wall of the left ventricle. Samples are also
taken from the proximal saphenous vein graft, the anastomoses site and the distal posterior coronary
artery as well as posterior left ventricle muscle wall. We also do a circumferential doughnut of the
right and left ventricle to see if any ischaemic damage has occurred. Routine blocks are also taken from
the proximal native vessels where there is significant atheroma. In this case microscopically
surprisingly we found diffuse acellular hyaline pink material throughout all the vessels both in the LIMA
graft, the vein graft and also in the epicardial coronary arteries as well as the intramural vessels.
The material was mainly in the media and appeared to be replacing the media with some proliferation of
the intima. There was no complete occlusion or thrombosis of the vessels. In the myocardium itself
there was no evidence of acute infarction or fibrosis and there was no evidence of this pink acellular
material in the muscle or interstitium of the heart itself. There was also widespread involvement of the
epicardial vessels. In addition, similar deposits were found in the pulmonary arteries, the
gastrointestinal tract, arteries, the spleen and liver with few vessels involved in the kidney.
Obviously, given the appearance it suggests amyloid. We did Congo red staining which confirmed this and
gave apple green birefringent with polarisation. Sections were sent for immunohistochemistry which were
negative for kappa and lamba chain and positive for transthyretin.
Senile Amyloid Involving Myocardium in Patient with Coronary Artery Disease and Bypass Surgery.
Case Discussion/Review of Literature
What is the role of senile amyloid in causing death after cardiac bypass surgery? This is a
Senile systemic amyloid, wild type (non mutant transthyretin) is the precursor protein of senile
systemic amyloid (SSA) and occurs predominantly in the heart. It is almost exclusively in men older than
65 years. This form of amyloid does have systemic distribution although clinically for this to be
evident, other than carpal tunnel syndrome which is common, or to cause any compromise is very unusual.
It has been considered a benign entity. Outside the heart, lung involvement predominates, but it can
also be found in the gastrointestinal tract, liver, spleen and endocrine glands. Autopsy studies suggest
that up to 22-36% of individuals older than 80 years have amyloid deposits in cardiac tissue but these
are generally not severe enough to affect cardiac function
Autopsy studies have revealed
amyloid also in the bone marrow and tongue, while kidney involvement is less common. Despite its benign
course, it may present with congestive cardiac failure with pronounced myocardial involvement. 
Isolated atrial amyloid (IAA) is one of the most common of the age related amyloids in the heart and
may play a role in atrial fibrillation. The pattern of IAA deposition was studied in 100 elderly
patients which increased with age, more pronounced in females with left atrial deposition being more
pronounced than right. The distribution was uneven being more pronounced in the anterior wall than in
both the posterior and left atrial appendage. IAA deposition was heavier in those patient s with a
history of chronic atrial fibrillation than in those with sinus rhythm . In contrast to the
pronounced male predominance in SSA, isolated atrial amyloid (IAA) is more common in older women. The
precursor protein in IAA is atrial natriuretic peptide which is deposited in the atria. There is no
systemic component to this type of amyloid. Although very prevalent in the elderly population and also
those with chronic heart failure, it is of little clinical significance, perhaps except for its
association with atrial fibrillation.
Most common amyloid to affect the heart in the ventricle is AL amyloidosis which is usually fatal
within 6 months of diagnosis the most common underlying disease being immunoglobulin light chain
gammopathy. The next most frequent is transthyretin-related hereditary amyloidosis which is due to a
mutant form of transthyretin (TTR).
Hereditary transthyretin-related amyloidosis (ATTR) is the most frequent form of familial systemic
amyloidosis, a group of severe diseases with variable neurological and organ involvement. There can be
extreme phenotypic variability: the clinical spectrum of the disease ranges from an almost exclusive
neurologic involvement to a strictly cardiac presentation. The most common mutation in TRR is Val30Met.
The existence of exclusively or predominantly cardiac phenotypes should lead clinicians to consider the
possibility of ATTR in all patients who present with an unexplained increase in left ventricular wall
thickness at echocardiography . It is noted in this case that most of the deposition of amyloid is in the
blood vessels in the media and adventitia with no total occlusion or thrombosis of the vessels. There is
none of the interstitial or nodular deposition that one sees typically with AL associated amyloid. While
some reviews state that senile amyloid is rarely symptomatic  a study of intramyocardial vascular
involvement in patients with primary amyloidosis (AL) and senile systemic amyloidosis (SSA) showed all
patients has focal transmural and vascular involvement by amyloid. In SSA the amyloid deposits were
concentrated largely in the adventitia and external media which is also what we found in this case. The
degree of vascular involvement and wall thickening is much great in AL than SSA. 
More recently senile systemic amyloidosis has been put forward as a cause of cardiac dysfunction in
individuals and probably contributes more to cardiac failure after cardiac bypass surgery than suspected
in the past . The clinicopathological features of senile systemic amyloidosis remains to be
completely understood. A post mortem study of 181 specimens in Japan showed senile amyloid being
deposited mainly in the subendocardium of the ventricular wall . In a Swedish study of both familial
and senile amyloid, all cases had deposits within the lungs . Two patterns have been described termed
pattern A found in all SSA and in some familial cases, had a homogeneous but patchy distribution within
the sub-endocardium, sub-epicardium, and myocardium; exhibited weak congophilia and green birefringence;
and composed of tightly packed, short, unorientated fibrils. This material contained 79-residue
C-terminal fragments of the amyloidogenic precursor protein. In pattern B, seen only in familial cases,
the amyloid appeared as thin streaks throughout the cardiac tissue; often surrounded individual muscle
cells; was strongly congophilic and birefringent; had long fibrils arranged in parallel bundles, often
penetrating into myocytes; and was composed of virtually intact TTR molecules.  There is
codeposition of apolipoprotein A-IV and transthyretin in senile systemic (ATTR) amyloidosis.
must also remember that you can get isolated valvular amyloidosis in association with calcification of
the aortic valve which also contains apo lipoprotein A. In the rare examples of gelsolin mutations it is
the conduction system of the heart which is uniquely affected.
It is not possible to distinguish between all types of amyloid by echocardiography. Cardiac magnetic
resonance (CMR) show global gadolinium late enhancement (GLE) in a subendocardial distribution. It is
highly sensitive and specific for the identification of cardiac involvement , but it does not
indicate prognosis simply by its presence. Diagnosis is done mainly by immunohistochemical confirmation
of transthyretin positivity in the amyloid. DNA analysis will show no mutations in senile amyloidosis.
While familial amyloid remains a slight possibility in our case, since DNA analysis was not undertaken,
the history and age of the patient points to this amyloid being the senile type.
This case emphasises that cardiac senile amyloid can play a role in death after cardiac surgery when
there is widespread vascular involvement. The widespread vascular involvement points to the coronary
circulation being unable to withstand the demands made and ischaemia associated with surgery and bypass.
There was no obvious problems with the coronary arteries or grafts during surgery and no ischaemic damage
in the myocardium at autopsy indicating the surgery had gone well. The cardiac arrest points to lack of
responsiveness of the coronary arteries to give an adequate blood supply within the epicardial and
intramural coronary vessels when the myocardium needed it in a hypertrophied ventricle. Death is
presumed due to a fatal arrhythmia.
The management of cardiac amyloidosis is based on the underlying cause. Treatment of senile systemic
amyloidosis is largely supportive. The therapeutic approaches for AL amyloidosis include chemotherapy,
autologous stem cell transplantation, and, rarely, cardiac transplantation. The familial variant is
potentially curable with a liver +/- cardiac transplantation. In SSA, IAA and AA amyloidosis no specific
disease modifying therapies exist.
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