Sea Anemone….To Treat or not to Treat:
That is the Question?
CT Surgery/Cardiology Conference
Shadwan Alsafwah, MD
Cardiology Fellow
University of Tennessee at Memphis
Case
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53 YO M with OSA was referred for OP routine
TTE for evaluation of pulmonary HTN.
PMH:
OSA
HTN
Hyperlipedemia
Asthma
Colon Polyposis
BPH
LUE weakness and tremor since 6 months
Case……
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Meds:
Albuterol
Lisinopril
Simvastatin
Terazosin
PSH:
Hernia repair
SH:
Smoker 1ppd X 30 y
No ETOH, illicit drugs
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Allergies:
Sulfa
Metronidazol
Codien
Case…
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Physical exam:
Vitals: 154/77, 65, 16, 97.7
Neck: No JVD, No Carotid Bruit.
Chest: CTAB
CVS: RRR, normal S1, S2, no extra sounds
Abdomen: Soft, NT, ND, NABS
Ext: No E/C/C
Neuro: Normal except for Motor 4/5 in LUE
2 D Echo
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EF: normal estimated 75%
Borderline mild pulmonary hypertension (peak
PA pressure 35-40 mm Hg.
Mild –moderate LVH
Fimbria-like structure on the aortic valve, most
likely papillary fibromatous tumor. Less likely to
be vegitation or Lambl’s Excrescence.
TEE recommended
TEE
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Fimbriae-like structure on the right coronary
cusp of the aortic valve C/W Papilary
fibroelastoma (not likely to be a lambl’s
excrescence, or vegetations)
Otherwise normal aorta
Normal LV function, EF 75%
Better Be Prepared for Questions like:
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What does this “structure” mean?
What caused it?
What should we do about it?
Outline
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Nomenclature
Historical Reference
Incidence
Natural History
Etiologies
Anatomy: - Gross
- Micro
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Clinical Manifestations
Diagnostic Modalities
Differential Diagnosis
Treatment
Prognosis
Summary
Nomenclature
Fibroma
Cardiac papiloma
Valvar papiloma
Myxofibroma
Fibroelastic hamartoma
Endocardiac papillary fibroma
Giant Lambl’s excrescences
Cardiac Papillary Fibroelastoma (CPF)
Historical Reference
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The first cardiac tumor ever described was a left atrial
myxoma described in 1845 by King TW :
“ On simple vascular growth in the left auricle
of the heart”
Lancet 1845;2:428-429.
Yater in 1931 was the first to describe the valvular
tumors
Cheitlin et al in 1975 used the term “papillary
fibroelastoma” for the first time.
Lichtenstein et al in 1979 were the first to report a
CPF found incidentally during VSD repair.
Flotte et al diagnosed this tumor on Echo 1980
Incidence
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Historically was the third most common benign
primary cardiac tumor after Myxomas, Lipomas
More recent series has placed it as the second most
common benign primary tumor of the adult heart.
The most common primary tumor of the cardiac
valves (3/4th)
Has an estimated incidence of 0.0017%-0.33% in
autopsy series, and an estimated echocardiography
incidence of 0.019%
Incidence…
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90% arise from valvular tissue, most commonly aortic
(44%) or mitral valves (35%). They may arise from
papilary muscles and chordae tendineae, but rarely
from the mural endocardium
Most commonly they arise from the mid portion of
the valve. They project into the arterial lumen of
semilunar valves and the atrial surface of AV valves
Reported from neonates to 92 years, but in general
rarely seen below age 20, with mean age of 60 years,
and 29% were 70 years of age or older.
Males = Females
Benign Primary Cardiac Tumors
Natural History
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Significant percentage of patients have concomittent
valvular disease, suggesting that prior endocardial
damage predisposes to papiloma formation
Generaly, Small in size:
- 99% <20 mm in largest dimension (mean 9 mm)
- Range 2-70 mm in size
More than 90% are solitary
Slow- grwoing tumor
Etiologies
Remains under discussion, possible etiologies:
 Truly neoplastic
 Viral
 Iatrogenic:
1. Post cardiac surgery
2. Post radiation therapy
 Other possible etiologies
(?) Viral
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Small study at Hospital Cardiologique, Chulille,
France.
4 patients with valvular CPF:
2 with prior neuro embolic events
2 without prior embolic events
CPFs were surgically removed, and all samples
were histologically confirmed
Specific immunohistochemical (IHC) studies
were conducted on all samples
Grandmougin D, et al. Heart Valve Dis 2000;9(6):832-41
(?) Viral
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The first 2 patients: there was good correlation between the
neuro events and the presence of thrombus aggregated on the
injured superficial endothelial layer.
The other 2 patients: no endothelial damage or thrombus were
found.
IHC studies showed:
-A centrifugal mesenchymal cellular migration arising from the
central layer to the superficial layer with differentiation steps.
-The presence of dendritic cells and remnants of CMV in the
intermediate layer.
Is CPF a chronic form of viral endocarditis.
Grandmougin D, et al. Heart Valve Dis 2000;9(6):832-41
(?) Iatrogenic
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A study at Mayo clinic and Armed forces Institute of
Pathology in washington, DC found 12 iatrogenic CPF cases
(6 post CT surgery, 6 post thoracic irradiation) between 19902000:
1. Common: It represented 18% of all surgically
excised CPF during that period!
2. Timing: mean interval was 18 years (range 9-31 years)
3. Multiple: about 58% were multiple!
4. Location: found in the chamber closest to the procedure, or
within the radiation field
5. Atypical: often involve nonvalvular endocardial surfaces
Kurup AN, et al. Hum Pathol 2002;33(12):1165-9
(?) Other Possible Etiologies
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Mechanical damage to the endothelium
Organizing thrombi
Hamartomous origin or congenital etiologies in
neonates/infants (very rare)
Gross Anatomy
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Resemble a sea
anemone:
Friable, white to tan
multiple branching
and nonbranching
fingerlike fronds
emanating from a
stalked central core
Microscopically
Each frond is avascular
and consists of a
collagenous core surrounded
by elastic fibers and loose
mucopolysaccharide matrix
with rare smooth muscle cells
And covered by a single layer
of endocardial endothelial cells
Clinical Manifestations
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More than 60% asymptomatic, found incidentally
Do not generally cause valvular dysfunction
But, sometimes can cause:
1. Embolic Phenomena leading to TIAs and CVAs:
- Can be as high as 25% over 3 years, and 6% in
asymptomatic incidental CPF
-Results from fragmentation of the papillary spikelets
of the tumor or from thrombi formed by platelets
and fibrin adhering to the uneven surface of CPF
-A/C of ? effect (3 cases with recurrent strokes while on A/C)
Other Clinical Manifestations..
- The tumor mobility was the only independent
predictor of CPF related death or nonfatal
embolization
2. Angina Pectoris, sometimes AMI if it involves
the coronary ostium
3. Outflow tract obstruction, presyncope or
syncope
4. Sudden death
5. It can get infected! (SBE prophylaxis?)
Diagnosis
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Should be suspected in young patients with no evidence of
cerebrovascular disease who present with an embolic cerebral
stroke, especially in the presence of NSR
Before 1977, they were diagnosed exclusively at postmortem
examination
Up to 1991 only 132 cases were reported in the literature
Now, it is generally an incidental finding by routine TTE
echocardiography (sensitivity 62%)
Best seen by TEE (sensitivity 77%)
Either TTE, TEE sensitivity is up to 90% if size >20 mm
Typical Echocardiographic Features
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Round, oval, irregular in appearance
Well-demarcated borders
Homogenous texture
Nearly half have small mobile stalk
TEE with its high resolution, may distinguish
the collagen center of the tumor from other
cardiac structures, due to its shining echo
appearance
It can rarely become calcified
Cardiac MRI and Ultrafast CT
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CPF are usually not seen at MRI or CT, due to their
size (very small in general) and location (moving valves)
Detects only exceptionally large CPF, or
atypical CPF (away from valves)
MRI is generally preferred to CT as it reflects the
chemical microenvironment within the tumor (better
soft-tissue characterization), offering clues to the type
of tumor
Will have more role in near future with new emerging
advances in technology?
Differential Diagnosis
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Lambl’s excrescences
Myxoma
Bacterial vegetations
Organizing marantic (thrombotic) endocarditis
CPF
Vs
Lambl’s
Excrescences
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Location: Valve surface
Rarely multiple
Gross: Small, branching
Micro: abundant
subendothelial myxoid
ground substance
Etiology: Multiple theories
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Very rare
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At sites of valve closure
> 90% multiple
Smaller, non branching
Less abundant
subendothelial myxoid
ground substance
Endothelial damage,
followed by thrombosis
and organization.
Common: more than 70%
of adults
Treatment
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Controversial, due to the absence of
randomized controlled data available
Long-term oral A/C +/- Antiplatelet therapy
could be offered to symptomatic patients who
are not surgical candidates, but its efficacy in
preventing embolic events is unclear.
SBE prophylaxis (?)
Sun JP, et al. Circualtion 2001;103:2687
Study Design
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Retrospective + Prospective 16-year study (1983- 1999) using
echo (total 109502 echos) and pathology data base at CCF.
162 patient found to have pathologically confirmed CPFs:
- in 141 an Echo (126 TTE, 107 TEE) was performed
-of those 93 CPFs identified: - 26 identified pre-surgery
(prospectively)
- 67 identified post-surgery
(retrospectively)
An additional 45 patients with presumed CPF identified by
echo database were followed for symptoms attributable to
CPF.
Sun JP, et al. Circulation 2001;103:2687
Sun, JP, et al. Circulation 2001;103:2687
Results
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23/26 patients in the Prospective group developed symptoms.
5/45 patients in the presumed group developed symptoms.
Stalks with mobility were present in almost all the symptomatic ones
Sun JP, et al. Circulation 2001;103:2687
Treatment of Right-sided CPF
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Right-sided CPF are less risky, surgery is not
completely agreed upon, but generally surgery
is indicated if:
1. Symptomatic
2. Large mobile tumors
3. Presence of PFO with a sizable right to left
shunt
Treatment of Left-sided CPF
Somewhat less controversial:
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In general: it should be removed, especially:
1. Symptomatic
2. CPF≥ 1 cm, especially if mobile
3. Young patients with low risk of surgery and
high risk for embolization
4. Patients with other cardiovascular disease.
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Asymptomatic patients with small, left-sided nonmobile CPF
can be followed-up closely with periodic clinical evaluations
and echo, and receive surgical intervention whenever
symptoms develop or the tumor becomes mobile
Prognosis
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Surgical removal is usually curative after
complete resection, never reported to recur in
the same location
CPF can recur in another location
More than 90% can be resected using
conservative valve- sparing approaches
Incidental CPF found on the aortic or mitral
valves during other surgery should be removed.
Long-term f/u is recommended
Back to Our Question:
Sea anemone: To treat or not to treat, that is the
question?
The best advise is:
Individualize, look at each case separately
Consider in your Decision..
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The Patient: -Age : the younger the pt the higher the
cumulative risk of embolization
-Other co-morbidities…
Symptomatic CPF or not
If symtomatic: what strength of association of the
tumor with symptoms
CPF Size (≥ or < 1 cm)
CPF Location (L sided or R sided, valvular or
nonvalvular…)
CPF mobility (i.e. presence of stalk or not)
Now Back to Our Patient
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He is 53 Y.O.
No major co morbidities/contraindications for surgery.
His CPF is on the Aortic valve
< 1 CM
nonmobile
The major question is whether the LUE weakness
represent an ischemic event or not.
Summary
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CPF is increasingly recognized with the widespread use
of TTE, TEE, and with new imaging modalities
It should be differentiated from other valvular
pathologies especially Lambl’s excrescences.
It can be symptomatic, mainly manifesting as embolic
disease
Controverseries still ongoing about the pathogenesis
and treatment of incidental CPF
More studies are needed to clarify its pathogenesis, and
treatment.
Thank You