Sea Anemone'To Treat or not to Treat: That is the Question

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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

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Case

• 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

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Case

• Meds
• Albuterol
• Lisinopril
• Simvastatin
• Terazosin
• PSH
• Hernia repair
• SH
• Smoker 1ppd X 30 y
• No ETOH, illicit drugs

• Allergies
• Sulfa
• Metronidazol
• Codien

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Case

• 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

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2 D Echo

• 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 Lambls Excrescence.
• TEE recommended

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TEE

• Fimbriae-like structure on the right coronary
  cusp of the aortic valve C/W Papilary
  fibroelastoma (not likely to be a lambls
  excrescence, or vegetations)
• Otherwise normal aorta
• Normal LV function, EF 75

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Better Be Prepared for Questions like

• What does this structure mean?
• What caused it?
• What should we do about it?

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Outline

• Nomenclature
• Historical Reference
• Incidence
• Natural History
• Etiologies
• Anatomy - Gross
• - Micro

• Clinical Manifestations
• Diagnostic Modalities
• Differential Diagnosis
• Treatment
• Prognosis
• Summary

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Nomenclature

• Fibroma
• Cardiac papiloma
• Valvar papiloma
• Myxofibroma
• Fibroelastic hamartoma
• Endocardiac papillary fibroma
• Giant Lambls excrescences
• Cardiac Papillary Fibroelastoma (CPF)

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Historical Reference

• 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
  18452428-429.
• 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

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Incidence

• 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

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Incidence

• 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

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Benign Primary Cardiac Tumors
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Natural History

• Significant percentage of patients have
  concomittent valvular disease, suggesting that
  prior endocardial damage predisposes to papiloma
  formation
• Generaly, Small in size
• - 99 lt20 mm in largest dimension (mean 9
  mm)
• - Range 2-70 mm in size
• More than 90 are solitary
• Slow- grwoing tumor

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Etiologies

• Remains under discussion, possible etiologies
• Truly neoplastic
• Viral
• Iatrogenic
• 1. Post cardiac surgery
• 2. Post radiation therapy
• Other possible etiologies

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(?) Viral

• 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 20009(6)832-41
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(?) Viral

• 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 20009(6)832-41
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(?) Iatrogenic

• 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 1990-2000
• 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 200233(12)1165-9
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(?) Other Possible Etiologies

• Mechanical damage to the endothelium
• Organizing thrombi
• Hamartomous origin or congenital etiologies in
  neonates/infants (very rare)

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Gross Anatomy

• Resemble a sea anemone
• Friable, white to tan multiple branching
• and nonbranching fingerlike fronds
  emanating from a stalked central core

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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

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Clinical Manifestations

• 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)

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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?)
  

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Diagnosis

• 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
  gt20 mm

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Typical Echocardiographic Features

• 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

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Cardiac MRI and Ultrafast CT

• 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?

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Differential Diagnosis

• Lambls excrescences
• Myxoma
• Bacterial vegetations
• Organizing marantic (thrombotic) endocarditis

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CPF Vs Lambls
Excrescences

• Location Valve surface
• Rarely multiple
• Gross Small, branching
• Micro abundant subendothelial myxoid ground
  substance
• Etiology Multiple theories
• Very rare

• At sites of valve closure
• gt 90 multiple
• Smaller, non branching
• Less abundant subendothelial myxoid ground
  substance
• Endothelial damage, followed by thrombosis
• and organization.
• Common more than 70 of adults

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Treatment

• 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 (?)

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Sun JP,
et al. Circualtion 20011032687
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Study Design

• 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 20011032687
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Sun, JP, et al. Circulation 20011032687Results

• 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 20011032687
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Treatment of Right-sided CPF

• 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

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Treatment of Left-sided CPF

• Somewhat less controversial
• 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.
• 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

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Prognosis

• 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

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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

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Consider in your Decision..

• 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 lt 1 cm)
• CPF Location (L sided or R sided, valvular or
  nonvalvular)
• CPF mobility (i.e. presence of stalk or not)

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Now Back to Our Patient

• He is 53 Y.O.
• No major co morbidities/contraindications for
  surgery.
• His CPF is on the Aortic valve
• lt 1 CM
• nonmobile
• The major question is whether the LUE weakness
  represent an ischemic event or not.

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Summary

• 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 Lambls 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.

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Thank You