Sea Anemone….To Treat or not to Sea Anemone….To Treat or not to Treat: That is the Question?Treat: That is the Question?

CT Surgery/Cardiology ConferenceCT Surgery/Cardiology ConferenceShadwan Alsafwah, MDShadwan Alsafwah, MD

Cardiology FellowCardiology Fellow University of Tennessee at MemphisUniversity of Tennessee at Memphis

CaseCase

53 YO M with OSA was referred for OP 53 YO M with OSA was referred for OP routine TTE for evaluation of pulmonary routine TTE for evaluation of pulmonary HTN.HTN.

PMH:PMH: OSAOSA HTNHTN HyperlipedemiaHyperlipedemia Asthma Asthma Colon PolyposisColon Polyposis BPHBPH LUE weakness and tremor since 6 LUE weakness and tremor since 6

monthsmonths

53 YO M with OSA was referred for OP 53 YO M with OSA was referred for OP routine TTE for evaluation of pulmonary routine TTE for evaluation of pulmonary HTN.HTN.

PMH:PMH: OSAOSA HTNHTN HyperlipedemiaHyperlipedemia Asthma Asthma Colon PolyposisColon Polyposis BPHBPH LUE weakness and tremor since 6 LUE weakness and tremor since 6

monthsmonths

Case……Case…… Meds:Meds:

AlbuterolAlbuterol

LisinoprilLisinopril

SimvastatinSimvastatin

TerazosinTerazosin PSH:PSH:

Hernia repairHernia repair SH:SH:

Smoker 1ppd X 30 ySmoker 1ppd X 30 y

No ETOH, illicit drugsNo ETOH, illicit drugs

Allergies:Allergies:

SulfaSulfa

MetronidazolMetronidazol

CodienCodien

Case…Case… Physical exam: Physical exam: Vitals: 154/77, 65, 16, 97.7Vitals: 154/77, 65, 16, 97.7 Neck: No JVD, No Carotid Bruit. Neck: No JVD, No Carotid Bruit. Chest: CTABChest: CTAB CVS: RRR, normal S1, S2, no extra CVS: RRR, normal S1, S2, no extra

soundssounds Abdomen: Soft, NT, ND, NABSAbdomen: Soft, NT, ND, NABS Ext: No E/C/C Ext: No E/C/C Neuro: Normal except for Motor 4/5 in Neuro: Normal except for Motor 4/5 in

LUE LUE

2 D Echo2 D Echo

EF: normal estimated 75%EF: normal estimated 75% Borderline mild pulmonary hypertension Borderline mild pulmonary hypertension

(peak PA pressure 35-40 mm Hg.(peak PA pressure 35-40 mm Hg. Mild –moderate LVH Mild –moderate LVH Fimbria-like structure on the aortic Fimbria-like structure on the aortic

valve, most likely papillary fibromatous valve, most likely papillary fibromatous tumor. Less likely to be vegitation or tumor. Less likely to be vegitation or Lambl’s Excrescence.Lambl’s Excrescence.

TEE recommendedTEE recommended

TEETEE

Fimbriae-like structure on the right Fimbriae-like structure on the right coronary cusp of the aortic valve coronary cusp of the aortic valve C/W Papilary fibroelastoma (not C/W Papilary fibroelastoma (not likely to be a lambl’s excrescence, or likely to be a lambl’s excrescence, or vegetations) vegetations)

Otherwise normal aortaOtherwise normal aorta Normal LV function, EF 75%Normal LV function, EF 75%

Better Be Prepared for Questions Better Be Prepared for Questions like:like:

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

OutlineOutline

NomenclatureNomenclature Historical Historical

ReferenceReference IncidenceIncidence Natural HistoryNatural History EtiologiesEtiologies Anatomy: - GrossAnatomy: - Gross

- Micro- Micro

Clinical Clinical ManifestationsManifestations

Diagnostic Diagnostic ModalitiesModalities

Differential Differential DiagnosisDiagnosis

TreatmentTreatment PrognosisPrognosis SummarySummary

NomenclatureNomenclature

FibromaFibroma Cardiac papilomaCardiac papiloma Valvar papilomaValvar papiloma MyxofibromaMyxofibroma Fibroelastic hamartomaFibroelastic hamartoma Endocardiac papillary fibromaEndocardiac papillary fibroma Giant Lambl’s excrescencesGiant Lambl’s excrescences Cardiac Papillary Fibroelastoma Cardiac Papillary Fibroelastoma

(CPF)(CPF)

Historical ReferenceHistorical Reference The first cardiac tumor ever described was a The first cardiac tumor ever described was a

left atrial myxoma described in 1845 by King left atrial myxoma described in 1845 by King TW :TW :

“ “ On simple vascular growth in the left auricle On simple vascular growth in the left auricle of the heart” of the heart” Lancet 1845;2:428-429. Lancet 1845;2:428-429.

Yater in 1931 was the first to describe the Yater in 1931 was the first to describe the valvular tumors valvular tumors

Cheitlin et al in 1975 used the term “papillary Cheitlin et al in 1975 used the term “papillary fibroelastoma” for the first time. fibroelastoma” for the first time.

Lichtenstein et al in 1979 were the first to Lichtenstein et al in 1979 were the first to report a CPF found incidentally during VSD report a CPF found incidentally during VSD repair.repair.

Flotte et al diagnosed this tumor on Echo 1980Flotte et al diagnosed this tumor on Echo 1980

IncidenceIncidence

Historically was the third most common Historically was the third most common benign primary cardiac tumor after Myxomas, benign primary cardiac tumor after Myxomas, Lipomas Lipomas

More recent series has placed it as the More recent series has placed it as the second most common benign primary tumor second most common benign primary tumor of the adult heart. of the adult heart.

The most common primary tumor of the The most common primary tumor of the cardiac valves (3/4cardiac valves (3/4thth))

Has an estimated incidence of 0.0017%-Has an estimated incidence of 0.0017%-0.33% in autopsy series, and an estimated 0.33% in autopsy series, and an estimated echocardiography incidence of 0.019% echocardiography incidence of 0.019%

Incidence…Incidence… 90% arise from valvular tissue, most 90% arise from valvular tissue, most

commonly aortic (44%) or mitral valves commonly aortic (44%) or mitral valves (35%). They may arise from papilary muscles (35%). They may arise from papilary muscles and chordae tendineae, but rarely from the and chordae tendineae, but rarely from the mural endocardiummural endocardium

Most commonly they arise from the mid Most commonly they arise from the mid portion of the valve. They project into the portion of the valve. They project into the arterial lumen of semilunar valves and the arterial lumen of semilunar valves and the atrial surface of AV valves atrial surface of AV valves

Reported from neonates to 92 years, but in Reported from neonates to 92 years, but in general rarely seen below age 20, with mean general rarely seen below age 20, with mean age of 60 years, and 29% were 70 years of age of 60 years, and 29% were 70 years of age or older. age or older.

Males = Females Males = Females

Benign Primary Cardiac Benign Primary Cardiac TumorsTumors

Natural HistoryNatural History

Significant percentage of patients have Significant percentage of patients have concomittent valvular disease, suggesting concomittent valvular disease, suggesting that prior endocardial damage predisposes that prior endocardial damage predisposes to papiloma formationto papiloma formation

Generaly, Small in size: Generaly, Small in size:

- 99% <20 mm in largest dimension (mean - 99% <20 mm in largest dimension (mean 9 mm)9 mm)

- Range 2-70 mm in size - Range 2-70 mm in size More than 90% are solitary More than 90% are solitary Slow- grwoing tumorSlow- grwoing tumor

EtiologiesEtiologies

Remains under discussion, Remains under discussion, possiblepossible etiologies:etiologies:

Truly neoplasticTruly neoplastic Viral Viral Iatrogenic: Iatrogenic:

1. Post cardiac surgery1. Post cardiac surgery

2. Post radiation therapy 2. Post radiation therapy Other possible etiologies Other possible etiologies

(?) Viral(?) Viral

Small study at Hospital Cardiologique, Small study at Hospital Cardiologique, Chulille, France. Chulille, France.

4 patients with valvular CPF: 4 patients with valvular CPF: 2 with prior neuro embolic events2 with prior neuro embolic events 2 without prior embolic events2 without prior embolic events CPFs were surgically removed, and all CPFs were surgically removed, and all

samples were histologically confirmed samples were histologically confirmed Specific immunohistochemical (IHC) Specific immunohistochemical (IHC)

studies were conducted on all samples studies were conducted on all samples

Grandmougin D, et al. Heart Valve Dis 2000;9(6):832-41

(?) Viral(?) Viral

The first 2 patients: there was good correlation between The first 2 patients: there was good correlation between the neuro events and the presence of thrombus the neuro events and the presence of thrombus aggregated on the injured superficial endothelial layer.aggregated on the injured superficial endothelial layer.

The other 2 patients: no endothelial damage or The other 2 patients: no endothelial damage or thrombus were found.thrombus were found.

IHC studies showed: IHC studies showed: -A centrifugal mesenchymal cellular migration arising -A centrifugal mesenchymal cellular migration arising

from the from the central layer to the superficial layer with central layer to the superficial layer with

differentiation steps.differentiation steps. -The presence of dendritic cells and remnants of CMV -The presence of dendritic cells and remnants of CMV

in the in the intermediate layer.intermediate layer. Is CPF a chronic form of viral endocarditis.Is CPF a chronic form of viral endocarditis.

Grandmougin D, et al. Heart Valve Dis 2000;9(6):832-41

(?) Iatrogenic(?) Iatrogenic

A study at Mayo clinic and Armed forces Institute of A study at Mayo clinic and Armed forces Institute of Pathology in washington, DC found 12 iatrogenic CPF Pathology in washington, DC found 12 iatrogenic CPF cases (6 post CT surgery, 6 post thoracic irradiation) cases (6 post CT surgery, 6 post thoracic irradiation) between 1990-2000:between 1990-2000:

1. Common: It represented 18% of all surgically 1. Common: It represented 18% of all surgically excised CPF during that period!excised CPF during that period! 2. Timing: mean interval was 18 years (range 9-31 2. Timing: mean interval was 18 years (range 9-31

years)years) 3. Multiple: about 58% were multiple!3. Multiple: about 58% were multiple! 4. Location: found in the chamber closest to the 4. Location: found in the chamber closest to the

procedure, or procedure, or within the radiation field within the radiation field 5. Atypical: often involve nonvalvular endocardial 5. Atypical: often involve nonvalvular endocardial

surfacessurfaces

Kurup AN, et al. Hum Pathol 2002;33(12):1165-9

(?) Other Possible (?) Other Possible EtiologiesEtiologies

Mechanical damage to the Mechanical damage to the endotheliumendothelium

Organizing thrombiOrganizing thrombi Hamartomous origin or congenital Hamartomous origin or congenital

etiologies in neonates/infants (very etiologies in neonates/infants (very rare)rare)

Gross AnatomyGross Anatomy

Resemble a sea Resemble a sea anemone:anemone:

Friable, white to Friable, white to tan multiple tan multiple branching branching

and nonbranching and nonbranching fingerlike fronds fingerlike fronds emanating from a emanating from a stalked central stalked central corecore

MicroscopicallyMicroscopically

Each frond is avascular Each frond is avascular

and consists of a and consists of a

collagenous core surrounded collagenous core surrounded

by elastic fibers and loose by elastic fibers and loose

mucopolysaccharide matrix mucopolysaccharide matrix

with rare smooth muscle cellswith rare smooth muscle cells

And covered by a single layer And covered by a single layer

of endocardial endothelial of endocardial endothelial cells cells

Clinical ManifestationsClinical Manifestations More than 60% asymptomatic, found incidentallyMore than 60% asymptomatic, found incidentally Do not generally cause valvular dysfunctionDo not generally cause valvular dysfunction But, sometimes can cause: But, sometimes can cause: 1. Embolic Phenomena leading to TIAs and CVAs: 1. Embolic Phenomena leading to TIAs and CVAs: - Can be as high as 25% over 3 years, and 6% in - Can be as high as 25% over 3 years, and 6% in asymptomatic incidental CPF asymptomatic incidental CPF -Results from fragmentation of the papillary -Results from fragmentation of the papillary

spikelets spikelets of the tumor or from thrombi formed by platelets of the tumor or from thrombi formed by platelets and fibrin adhering to the uneven surface of CPF and fibrin adhering to the uneven surface of CPF

-A/C of ? effect (3 cases with recurrent strokes -A/C of ? effect (3 cases with recurrent strokes

while on A/C) while on A/C)

Other Clinical Other Clinical Manifestations..Manifestations..

- - The tumor mobility was the only The tumor mobility was the only independent predictor of CPF related independent predictor of CPF related death or nonfatal embolization death or nonfatal embolization

2. Angina Pectoris, sometimes AMI if it 2. Angina Pectoris, sometimes AMI if it involves the coronary ostium involves the coronary ostium

3. Outflow tract obstruction, presyncope or 3. Outflow tract obstruction, presyncope or

syncope syncope 4. Sudden death 4. Sudden death 5. It can get infected! (SBE prophylaxis?) 5. It can get infected! (SBE prophylaxis?)

               

               

              

               

               

DiagnosisDiagnosis Should be suspected in young patients with no Should be suspected in young patients with no

evidence of cerebrovascular disease who present evidence of cerebrovascular disease who present with an embolic cerebral stroke, especially in the with an embolic cerebral stroke, especially in the presence of NSRpresence of NSR

Before 1977, they were diagnosed exclusively at Before 1977, they were diagnosed exclusively at postmortem examinationpostmortem examination

Up to 1991 only 132 cases were reported in the Up to 1991 only 132 cases were reported in the literatureliterature

Now, it is generally an incidental finding by Now, it is generally an incidental finding by routine TTE echocardiography (sensitivity 62%) routine TTE echocardiography (sensitivity 62%)

Best seen by TEE (sensitivity 77%)Best seen by TEE (sensitivity 77%) Either TTE, TEE sensitivity is up to 90% if size Either TTE, TEE sensitivity is up to 90% if size

>20 mm >20 mm

Typical Echocardiographic Typical Echocardiographic FeaturesFeatures

Round, oval, irregular in appearance Round, oval, irregular in appearance Well-demarcated borders Well-demarcated borders Homogenous textureHomogenous texture Nearly half have small mobile stalk Nearly half have small mobile stalk TEE with its high resolution, may TEE with its high resolution, may

distinguish the collagen center of the distinguish the collagen center of the tumor from other cardiac structures, tumor from other cardiac structures, due to its shining echo appearance due to its shining echo appearance

It can rarely become calcifiedIt can rarely become calcified

Cardiac MRI and Cardiac MRI and Ultrafast CTUltrafast CT

CPF are usually not seen at MRI or CT, due to CPF are usually not seen at MRI or CT, due to their size (very small in general) and location their size (very small in general) and location (moving valves)(moving valves)

Detects only exceptionally large CPF, or Detects only exceptionally large CPF, or atypical CPF (away from valves) atypical CPF (away from valves) MRI is generally preferred to CT as it reflects MRI is generally preferred to CT as it reflects

the chemical microenvironment within the the chemical microenvironment within the tumor (better soft-tissue characterization), tumor (better soft-tissue characterization), offering clues to the type of tumoroffering clues to the type of tumor

Will have more role in near future with new Will have more role in near future with new emerging advances in technology? emerging advances in technology?

Differential DiagnosisDifferential Diagnosis

Lambl’s excrescencesLambl’s excrescences MyxomaMyxoma Bacterial vegetationsBacterial vegetations Organizing marantic (thrombotic) Organizing marantic (thrombotic)

endocarditisendocarditis

CPF Vs Lambl’s CPF Vs Lambl’s Excrescences Excrescences

Location: Valve surfaceLocation: Valve surface Rarely multipleRarely multiple Gross: Small, branching Gross: Small, branching

Micro: abundant Micro: abundant

subendothelial myxoid subendothelial myxoid ground substanceground substance

Etiology: Multiple Etiology: Multiple theoriestheories

Very rareVery rare

At sites of valve closureAt sites of valve closure > 90% multiple> 90% multiple Smaller, non branching Smaller, non branching Less abundant Less abundant

subendothelial myxoid subendothelial myxoid ground substanceground substance

Endothelial damage, Endothelial damage, followed by thrombosis followed by thrombosis

and organization.and organization. Common: more than Common: more than

70% of adults70% of adults

TreatmentTreatment

Controversial, due to the absence of Controversial, due to the absence of randomized controlled data availablerandomized controlled data available

Long-term oral A/C +/- Antiplatelet Long-term oral A/C +/- Antiplatelet therapy could be offered to therapy could be offered to symptomatic patients who are not symptomatic patients who are not surgical candidates, but its efficacy surgical candidates, but its efficacy in preventing embolic events is in preventing embolic events is unclear.unclear.

SBE prophylaxis (?) SBE prophylaxis (?)

Sun JP, et al. Circualtion 2001;103:2687

Study DesignStudy Design

Retrospective + Prospective 16-year study (1983- 1999) Retrospective + Prospective 16-year study (1983- 1999)

using echo (total 109502 echos) and pathology data base using echo (total 109502 echos) and pathology data base at CCF.at CCF.

162 patient found to have pathologically confirmed CPFs:162 patient found to have pathologically confirmed CPFs: - in 141 an Echo (126 TTE, 107 TEE) was performed- in 141 an Echo (126 TTE, 107 TEE) was performed -of those 93 CPFs identified: - 26 identified pre--of those 93 CPFs identified: - 26 identified pre-

surgery surgery (prospectively)(prospectively) - 67 identified post-- 67 identified post-

surgerysurgery (retrospectively) (retrospectively)

An additional 45 patients with presumed CPF identified An additional 45 patients with presumed CPF identified

by echo database were followed for symptoms by echo database were followed for symptoms attributable to CPF. attributable to CPF.

Sun JP, et al. Circulation 2001;103:2687

Sun, JP, et al. Circulation Sun, JP, et al. Circulation 2001;103:26872001;103:2687

ResultsResults

23/26 patients in the Prospective group developed symptoms.23/26 patients in the Prospective group developed symptoms. 5/45 patients in the presumed group developed symptoms.5/45 patients in the presumed group developed symptoms. Stalks with mobility were present in almost all the Stalks with mobility were present in almost all the

symptomatic ones symptomatic ones

Sun JP, et al. Circulation 2001;103:2687

Treatment of Right-sided Treatment of Right-sided CPFCPF

Right-sided CPF are less risky, Right-sided CPF are less risky, surgery is not completely agreed surgery is not completely agreed upon, but generally surgery is upon, but generally surgery is indicated if:indicated if:

1. Symptomatic1. Symptomatic

2. Large mobile tumors 2. Large mobile tumors

3. Presence of PFO with a sizable 3. Presence of PFO with a sizable right to left right to left

shunt shunt

Treatment of Left-sided Treatment of Left-sided CPFCPF

Somewhat less controversial:Somewhat less controversial: In general: it should be removed, especially:In general: it should be removed, especially: 1. Symptomatic1. Symptomatic 2. CPF≥ 1 cm, especially if mobile2. CPF≥ 1 cm, especially if mobile 3. Young patients with low risk of surgery and 3. Young patients with low risk of surgery and high risk for embolizationhigh risk for embolization 4. Patients with other cardiovascular disease.4. Patients with other cardiovascular disease. Asymptomatic patients with small, left-sided Asymptomatic patients with small, left-sided

nonmobile CPF can be followed-up closely with nonmobile CPF can be followed-up closely with periodic clinical evaluations and echo, and periodic clinical evaluations and echo, and receive surgical intervention whenever symptoms receive surgical intervention whenever symptoms develop or the tumor becomes mobile develop or the tumor becomes mobile

PrognosisPrognosis

Surgical removal is usually curative Surgical removal is usually curative after complete resection, never after complete resection, never reported to recur in the same locationreported to recur in the same location

CPF can recur in another location CPF can recur in another location More than 90% can be resected using More than 90% can be resected using

conservative valve- sparing approaches conservative valve- sparing approaches Incidental CPF found on the aortic or Incidental CPF found on the aortic or

mitral valves during other surgery mitral valves during other surgery should be removed.should be removed.

Long-term f/u is recommendedLong-term f/u is recommended

Back to Our Question:Back to Our Question:

Sea anemone: To treat or not to treat, Sea anemone: To treat or not to treat, that is the question?that is the question?

The best advise is:The best advise is:

Individualize, look at each case Individualize, look at each case separatelyseparately

Consider in your Consider in your Decision..Decision..

The Patient: -Age : the younger the pt the The Patient: -Age : the younger the pt the higher the higher the

cumulative risk of cumulative risk of embolizationembolization

-Other co-morbidities…-Other co-morbidities… Symptomatic CPF or notSymptomatic CPF or not If symtomatic: what strength of association If symtomatic: what strength of association

of the tumor with symptomsof the tumor with symptoms CPF Size (≥ or < 1 cm)CPF Size (≥ or < 1 cm) CPF Location (L sided or R sided, valvular CPF Location (L sided or R sided, valvular

or nonvalvular…)or nonvalvular…) CPF mobility (i.e. presence of stalk or not) CPF mobility (i.e. presence of stalk or not)

Now Back to Our PatientNow Back to Our Patient

He is 53 Y.O.He is 53 Y.O. No major co morbidities/contraindications No major co morbidities/contraindications

for surgery.for surgery. His CPF is on the Aortic valveHis CPF is on the Aortic valve

< 1 CM< 1 CM

nonmobile nonmobile The major question is whether the LUE The major question is whether the LUE

weakness represent an ischemic event weakness represent an ischemic event or not.or not.

SummarySummary CPF is increasingly recognized with the CPF is increasingly recognized with the

widespread use of TTE, TEE, and with new widespread use of TTE, TEE, and with new imaging modalitiesimaging modalities

It should be differentiated from other valvular It should be differentiated from other valvular pathologies especially Lambl’s excrescences.pathologies especially Lambl’s excrescences.

It can be symptomatic, mainly manifesting as It can be symptomatic, mainly manifesting as embolic diseaseembolic disease

Controverseries still ongoing about the Controverseries still ongoing about the pathogenesis and treatment of incidental CPF pathogenesis and treatment of incidental CPF

More studies are needed to clarify its More studies are needed to clarify its pathogenesis, and treatment.pathogenesis, and treatment.

Thank YouThank You