3. The term 'endomyocardial disease' includes endomyocardial
fibrosis and Loffler's endocarditis parietalis fibroplastica
(Loffler's endomyocardial disease)which have long been
considered separate entities.
Endomyocardial fibrosis was believed to be confined
to the tropical regions, and Loffler's endomyocardial
disease to temperate zones and associated with
eosinophilia
The geographical limitations of the tropical type of
endomyocardial fibrosis, suggesting confinement to the
African continent, has proved unwarranted .
4. An association with eosinophils in the pathogenesis
of endomyocardial fibrosis was suggested by Davies
and Ball (1955).
Subsequently, Parry and Abrahams (1965) noted
patients in Nigeria, either diagnosed as Loffler's
disease or heart muscle disease due to filariasis.
Europeans, working in the tropical zones who
developed endomyocardial fibrosis in association with
eosinophils, were described by Brockington, Olsen
and Goodwin (1967).
5.
6.
7.
8. Definition
Endomyocardial fibrosis (EMF) is an obliterative
cardiomyopathy of uncertain etiology, with fibrotic
deposits on the endocardial surface of the apices and
inflow of either or both ventricles.
It is a progressive cardiac disease characterized by
swelling of the endocardial connective tissue, with
accumulation of acid mucopolysaccharides in the
endocardium followed by scarring and fibrosis.
It may affect one or both ventricles primarily, and the
other cardiac chambers to a lesser extent,not accompanied
by lesions in any other part of the body (except when
there is embolization).
9. Internationally: EMF occurs primarily in the subtropical
regions of Africa but is also encountered in tropical and
subtropical regions elsewhere in the world, including areas
in India and South America that are within 15° of the
equator.
More than 90% of reported cases of EMF have occurred in
geographic locations that are within 15° of the equator.
In equatorial African nations, such as Nigeria, EMF is the
fourth most common cause of cardiac disease in adults,
and EMF accounts for 22% of cases of heart failure in
Nigerian children.
EMF is the most common type of restrictive
cardiomyopathy in tropical countries
10. EMF - India
First identified – Dr. Ball , CMC , Vellore
First publication – Samuel & Anklesaria
Gopi etal – described features of RV EMF
Vijayaraghavan etal , cherian etal – described the
clinical , radiological , hemodynamic and
angiographic features of LV/RV EMF in south India
11. Incidence
Africa – 10 -12 % of all heart disease
- MC cause of cardiomyopathy
- 3-25 % of autopsies
• India – south – 5-7 % of all admissions ( Nair etal)
- North - < 5 % of all admissions
- 0.75 % of all autopsies ( wahi etal)
12. EMF is primarily a disease of the young, occurring in
children, adolescents and young adults.
In Uganda, a bimodal peak at ages 10 and 30 has been
observed, and a similar pattern was recently found in
Mozambique.
The differences between genders in the frequency of
disease have been variable .
ages varied from 7 to 31 years. (vijaya raghavan
et .,al)
13. Ventricular chamber affected..
Africa – LV – 40%
RV – 10 %
Bi V – 50 %
• India - South ( vijayaraghavan etal ) –
RV – 60 %
LV – 20 %
BiV – 20 %
- North (wahi etal ) –
RV – 20 %
LV – 40 %
Bi V – 40 %
14. Etiology
Abraham , shaper , cadell et al – unusual expression
of rheumatic process
Vendergeld et al – autoimmunity- antiheart ab
Connor et al – multifactorial hypothesis
Seyle et al – malnutrition , Mg , K loss
Crawford etal –ingestion of serotonin rich food
Grey et al,miller et al – Loa loa infection
Smith & furth – chronic beriberi
15. Etiology
EMF is most frequently observed in the socially disadvantaged and in
children and young women.
These groups frequently have malnutrition, and in regions of sub-
Saharan Africa where the disease is most prevalent, the typical diet is
high in a tuber called cassava, which contains relatively high
concentrations of the rare earth element cerium (Ce).
The combination of high Ce levels and hypomagnesemia produced
EMF-like lesions in laboratory animals.
A familial tendency has rarely been noted in Uganda and Zambia
16. Etiology
Causes: A specific single etiology of EMF has not been
established. Suggested potential causes include the following:
Infectious causes
Parasites (eg, helminths)
Protozoans (eg, toxoplasmosis, malaria)
Inflammatory causes - Eosinophilia
Nutritional causes
General malnutrition
High-tuber diet
Ce toxicity
Hypomagnesemia
17.
18.
19. Pathophisiology
Edington & jackson – Basic lesion in heart muscle ,sec
changes in Endo/sub-endocardium
Davies & Ball – predominant endocardial involvement
Mehrotra etal – degeneration of myocardium
Kinare & deshpande – interstitial fibrosis & atrophy of
the myocardium
Samuel etal – myocardial degeneration
Reddy etal - myocytolysis
20. Pathophysiology
In EMF, patchy fibrosis of the endocardial surface of
the heart, leads to reduced compliance and, ultimately,
restrictive physiology as the endomyocardial surface
becomes more generally involved.
Endocardial fibrosis principally involves the inflow tracts
of the right and left ventricles and may affect the
atrioventricular valves, leading to tricuspid and mitral
regurgitation.
21. Macroscopically, the hearts are hypertrophied and
the ventricular cavity may be dilated or reduced in
size.
The striking feature is the immense thickening
of the endocardium, often several millimeters in
dimension.
Strands of fibrous tissue frequently extend into the underlying
myocardium, usually, limited to the inner third of the
myocardial wall (Davies and Ball, 1955; Olsen, 1972).
The right ventricle (11%), the left ventricle (38%) or both
ventricles (51%) may be involved (Shaper, Hutt and Coles, 1968).
22. Pathophysiology 25
•The earliest changes of EMF are not well described
because most patients do not present with symptoms until
relatively late in the clinical course.
o Olsen described 3 phases of EMF.
•The first phase involves eosinophilic infiltration of the
myocardium with necrosis of the subendocardium and a
pathologic picture consistent with acute myocarditis. This is
reportedly present in the first 5 weeks of the illness.
The second stage, typically observed after 10 months, is
associated with thrombus formation over the initial lesions,
with a decrement in the amount of inflammatory activity
present.
23.
24. Ultimately, after several years of disease activity, the
fibrotic phase is reached, when the endocardium is
replaced by collagenous fibrosis.
Extensive calcification is rarely associated with
fibrosis.
This pathomorphologic scheme is not observed
uniformly and has not been consistently supported by
other investigators.
27. Typically, in right-sided involvement, the apex is
affected, gradually being drawn towards the tricuspid
valve, which may also be affected by this process
Thus, the cavity is progressively obliterated.
The chordae tendineae and papillary muscles may
also be involved.
In left ventricular involvement, the inflow tract,
apex and part of the outflow tract is usually affected.
(Olsen)
The thick endocardium ends, usually abruptly, in a
rolled edge in the region beneath the anterior mitral
valve leaflet (Davies)
28. In 68% of patients, the posterior mitral leaflet is
involved and may be reduced to little more than a
fibrous ridge, permitting mitral regurgitation which
does not always produce the typical murmur on
auscultation
The valve leaflets otherwise remain intrinsically
normal unless there is bacterial or rheumatic
infection.
Gradually, obliteration of the ventricular apex
occurs which, with cicatrization, reduces the volume
and alters the shape of the affected ventricular
chamber
30. Left Ventricle:
The region most commonly involved was the
posterior wall (29/30 cases), closely followed by the
apex and lateral wall (both 25/30 cases); the septal
wall was less frequently affected (15/30)(Davies et.,al)
31. In the later stages of right ventricular disease, tricuspid
incompetence causes a very large "paper-thin" right
atrium, with massive thrombi in the atrial appendage.
These sometimes extend into the superior vena cava or
the veins draining into it.
The right ventricle becomes contracted and distorted,
with a hypertrophied, dilated outflow tract.
In left-sided involvement, the left atrium is enlarged,
unless partially protected by the low flow rates of
biventricular disease.
The right coronary artery is displaced by the bulging of
the atrioventricular groove, but the coronary lumen is not
compromised on either side.
43. Histologic Findings: The heart size is not usually
enlarged in EMF.
The ventricular cavities are frequently laden with
thrombi and, in severe cases, may be nearly totally
obliterated by endocardial thickening and
thrombosis.
The histologic findings are characterized by reactive
fibrosis with a selective increase in type I collagen
deposition, subendocardial infarction and fibrosis,
and thrombus formation.
Additionally, specific features of other diseases, such
as those associated with hemochromatosis or
44. Hassan, W. M. et al. Chest 2005;128:3985-3992
Photomicrograph of endomyocardial biopsy specimen showing marked
thickening of the endocardium (E) with fibrosis (hematoxylin-eosin, original x
200)
45. Clinical features
Sex: Women of reproductive age and children are more
commonly affected than men.
Age:
EMF is not generally observed in children younger than 4
years, although the typical pathology for EMF has recently
been described in a 4-month-old infant with left
ventricular inflow tract obstruction.
The people most commonly affected are older children
(aged 5-15 y) and young adults, but cases have been
reported in individuals aged 70 years.
46. Clinical features
50
History: Typically, endomyocardial fibrosis (EMF) has an
insidious onset, and symptoms relate to the specific
chambers and valves where the disease is most extensive.
The triad of raised jugular venous pressure, hepatomegaly,
and ascites characterize of right ventricular
endomyocardial fibrosis (VijayaRaghavan et.,al)
When right ventricular involvement or tricuspid
regurgitation predominates, lower extremity swelling,
increasing abdominal girth, and nausea may be expected.
47. With left ventricular involvement, dyspnea is the
predominant symptom, especially exertional dyspnea.
Additionally, fatigue, paroxysmal nocturnal dyspnea, and
orthopnea may be present.
Thromboembolic complications may occur in EMF.
Rarely, patients may present early in the course of the
disease with an acute febrile illness with symptoms of
cardiac insufficiency mimicking myocarditis.
Recently, angina like chest pain and syncope were
reported in a patient with EMF involving the left
ventricle
48. Physical: Physical findings are also dependent on the extent
and distribution of disease.
In those with right ventricular involvement, jugular venous
pressure elevation, ascites, and edema may be present.
The presence of ascites may appear out of proportion to the
amount of peripheral edema.
Patients with tricuspid regurgitation may have giant V
waves.
A S3 or S4 and tachycardia may be present.
49.
50. Patients with Isolated RVEMF with severe tricuspid
regurgitation (TR) present with features of chronic right heart
failure with markedly elevated JVP and expansile large ‘v’ waves,
pulsatile liver, hepatomegaly, ascites, oedema, cyanosis,
cachexia and malnutrition.
They may also have pericardial effusion, marked
cardiomegaly, RV S3, and inconspicuous
systolic murmur of TR.
The severity of TR rather than the presence of RV diastolic
dysfunction is the more important determining factor for the
clinical outcome of patients
An occasional patient with severe RVEMF can have cyanosis
due to right-to-left atrial shunting through a patent and
stretched fossa ovalis defect.
51. Left-sided disease.
Signs of pulmonary congestion are present in patients
with Signs of pulmonary hypertension and left heart
failure are out of proportion to the degree of MR
Isolated LVEMF, in the absence of AV valve
incompetence, is often minimally symptomatic.
Hemodynamic study may reveal a prominent ‘a’ wave in
the PA wedge pressure, and LV end diastolic pressure may
be elevated.
52. Other Problems to be Considered:
Anthracycline toxicity
Carcinoid heart disease
Drug-induced cardiotoxicity (eg, serotonin, methysergide,
ergotamine, mercurial agents, busulfan)
Fabry disease
Fatty infiltration
Gaucher disease
Glycogen storage disease
Hurler disease
Idiopathic cardiomyopathy
Metastatic cancers
Radiation
Rheumatic heart disease
Occasionally, a masslike lesion seen in endomyocardial fibrosis
masquerades as an intracardiac tumor.
53. Lab Studies:
Complete blood cell count may show anemia and
eosinophilia
Imaging Studies:
Chest radiography
The cardiac silhouette in endomyocardial fibrosis
(EMF) may be normal in size, and generalized
cardiomegaly is unusual
Significant enlargement of the atria, and significant
right atrial enlargement creates a cardiac silhouette in
the shape of the African continent, (‘Heart of Africa.’)
54. Electrocardiography
Atrial fibrillation – more common in RVEMF than in
LVEMF
Low QRS voltage
First-degree AV block in up to 44% of patients
Incomplete RBBB in up to 30% of patients
IN RV EMF – ‘p’ pulmonale , RVH , QR pattern in V 1 ,
Q in inf leads
In LVEMF – ‘p’ mitrale , LVH
55. CXR
On chest radiographs,esp. in RVEMF the heart is always
enlarged in the transverse diameter, and often it is enormous.
This may be due to a coexisting pericardial effusion, but is
usually due to a dilated, almost aneurysmal right atrium.
If pericardial fluid is scanty there will be an outflow tract
convexity, which on fluoroscopy or ultrasound is seen to be
very active.
56. In late cases there may be an oblique, linear calcification at the
elevated apex of the right ventricle or base of the pulmonary
conus .
The lung fields are strikingly oligemic and, because of low
cardiac output, the superior vena cava and azygos veins are
very prominent.
In LV EMF , myocardial calcification and pulmonary congestion
may be seen with a moderate cardiomegaly
58. The patterns of calcification in EMF. The top row shows
the typical linear oblique pattern of right-sided disease.
The lower row displays the curvilinear left ventricular
form.
59. Echocardiography
Echocardiography is a useful tool when making the
diagnosis of EMF and has been demonstrated to
successfully differentiate EMF and other processes.
The presence and location of fibrosis as determined by
echocardiography correlates well with autopsy findings.
Findings include thickening of the inferior and basal
left ventricular wall, apical obliteration, thrombi
adherent to endocardial surface, mitral regurgitation,
and tricuspid regurgitation.
60. A pericardial effusion is frequently present and may
be large.
Diastolic function by Doppler echocardiography tend to
correlate with the functional status of the patient.
most patients present with later stages of EMF, a
restrictive filling pattern in the left ventricular
outflow tract is most common.
Recently, decreased flow propagation velocity (Vp)
Color-flow imaging frequently exhibits tricuspid and
mitral regurgitation.
Spectral Doppler analysis of tricuspid regurgitation
frequently reflects an increased pulmonary artery
systolic pressure.
61. Echocardiography
Features of RV EMF –
Dilated RVOT
Partially obliterated RV cavity/ inflow tract fibrosis
Thickened IVS near the apical region
Hugely dilated RA
‘Notch’ on the epicardial surface near the apex of the
RV – occurs in advanced disease
Pericardial effusion
Restriction of movement of tricuspid valve cusps
62. Echocardiography
Features of LV EMF –
Involvement of the posterior cusp and the posterior
papillary muscle (unlike in RHD , AML is spared)
Obliteration of LV apex
Presence of areas of dyskinesia and aneurysmal
dilatation
63.
64. Hassan, W. M. et al. Chest 2005;128:3985-3992
Bidimensional echocardiographic apical two-chamber view of a patient with left-
sided EMF (top, a) and a four-chamber view of a patient with right-sided EMF
(bottom, b)
67. Electron beam computed
tomography scanning
Features of EMF observed with this modality were
described in the mid 1990s.
The fibrotic process is delineated as a band of low
attenuation within the endocardium.
Obliteration of the apex and inflow tract, when present,
is also demonstrated.
This method reportedly assists in distinguishing EMF
from constrictive pericarditis.
68. Cardiovascular magnetic
resonance imaging
Recently, the use of cardiovascular magnetic
resonance imaging has been shown to demonstrate
obliterative changes in the ventricles, atrial
dilation, and regurgitant atrioventricular valve
lesions in patients with EMF.
However, the use of contrast-enhanced imaging was
not able to demonstrate fibrosis within the ventricles
of these patients.
69. Steady-state free-precession 4-chamber view cine
MRI demonstrates right and left atrial dilatation and TR, with the
origin of the TR jet dislocated toward the apex of the right ventricle
(RV; arrow), possibly secondary to papillary muscle fibrosis
74. Procedures:
Cardiac catheterization likely exhibits
hemodynamic findings consistent with restrictive
cardiomyopathy.
Findings from endomyocardial biopsy may be
diagnostic, but this procedure is typically not
needed.
Biopsy findings may be nondiagnostic when the
disease is patchy and sampling sites do not
correlate with areas of disease.
Because biopsy (especially from the left
ventricle) carries some risk, reserve the use of
75. Hassan, W. M. et al. Chest 2005;128:3985-3992
Right-heart pressure tracing in a patient with right-sided EMF showing increased
right atrial pressure with a prominent A wave that is seen also in the right
ventricular and pulmonary artery (PA) tracings
76. Hassan, W. M. et al. Chest 2005;128:3985-3992
Right and left heart pressure tracing in a patient with biventricular EMF showing
elevated RA, RV, pulmonary artery (PA), left ventricular end-diastolic pressure,
and pulmonary capillary (P) wedge pressures
78. Angiography
Traditionally, angiography has been considered the
criterion standard when making the diagnosis of EMF.
Left and right ventriculography exhibits distortion of
chamber morphology by fibrosis and obliteration and
variable degrees of mitral and tricuspid regurgitation.
The mushroom sign has been used to describe the
shape of the affected ventricle when the apex is
obliterated completely by fibrosis.
79. Angiocardiography
Features of RV EMF –
1) Aneurysmal dilatation of RA
2)Small and fibrosed inflow tract of RV
3)Dilated , hyperdynamic outflow region
4)Normally placed tricuspid valve
81. Angiocardiography
RV EMF – Grading
Grade 1 – Minimal involvement of RV chamber in the form
of alterations in the trabecular pattern at the apex
and along the septal border with irregular filling defects
Grade 2 – Obliteration of the apex and adjacent
border of the RV chamber ,but not extending up to the
tricuspid annulus
Grade 3 – Obliteration of the RV chamber including the
area near the tricuspid annulus ,but sparing the RV
outflow
Grade 4 – Involvement of the RV body as well as
narrowing of the outflow tract
82. Angiocardiography
LV EMF – Grading –
Grade 1 – Generalised smoothening of the LV wall
with small irregular filling defects at the apex
Grade 2 – Obliteration of the apical area of the LV
chamber in addition to a smooth border and irregular
filling defects
Grade 3 – Obliteration of roughly half or more of
the LV cavity
83. Hassan, W. M. et al. Chest 2005;128:3985-3992
Left ventricular angiogram in the right anterior oblique view showing obliteration
of the apex (arrow) in systole (top, a) and diastole (bottom, b)
84. Hassan, W. M. et al. Chest 2005;128:3985-3992
Right ventricular angiogram in the right anterior oblique view in a patient with
right-sided EMF showing complete obliteration of the apex of the right ventricle,
dilated right atrium, and severe TR
91. Diagnosis
Routine radiography will be of great
assistance in right-sided dominance, but
echocardiography and angiocardiography are
important, particularly in distinguishing left-
sided EMF from rheumatic disease.
MRI may replace angiography except in
some preoperative patients.
92. Panel A. Fibrotic left ventricle (LV) apical infiltration (arrow).
LA, left atrium.
Panel B. Left ventriculography showing the amputated LV apex
(arrow).
Panel C. TV (white arrow); diffuse RV fibrotic infiltration (black
arrow).
Panel D. Contrast medium in the superior cava vein (black arrow) descending through the right
pulmonary artery (white arrow
93. Prognosis :
Prognosis for this condition is poor.
Incidence of sudden cardiac death from fatal
arrhythmias or from progressive cardiac failure is
high.
Most patients have extensive disease at the time
of presentation; therefore, survival after diagnosis
is relatively brief.
In one study, 95% of a group of patients had died
at 2 years.
In a second study, 44% of patients died within 1
year after the onset of symptoms.
94. Treatment
Medical Care:
In general, the response to medical therapy is poor and
unproven.
Because most patients with endomyocardial fibrosis
(EMF) present long after any possible period of early
active myocarditis may have existed, little role exists for
immunosuppressive therapy .
Symptomatic therapy with diuretics has been shown to be
useful, but digoxin, afterload reducers, and beta-blockers
have little role in EMF.
95. For patients with severe symptoms, consider surgical
therapy because the prognosis for these patients with
continued medical therapy alone is dismal.
Because the rate of thromboembolism is low among
patients with EMF
The patient population affected is not typically compliant
with anticoagulation regimens.
most authors do not recommend anticoagulant therapy.
96. Treatment
Surgical Care:
Surgical therapy by endocardial decortication seems to
be beneficial for many patients with advanced disease who
are in functional-therapeutic class III or IV.
The operative mortality rate is high (15-20%), but
successful surgery has a clear benefit on symptoms and
seems to favorably affect survival as well.
The most commonly used approach is endocardiectomy,
combined with mitral and/or tricuspid repair or
replacement (when indicated), using a midline
thoracotomy and cardiopulmonary bypass.
97. In 1971, Dubost et al.41 had introduced surgical
treatment of EMF by endocardial decoritication and
AV valve replacement.
A plane of cleavage can be easily developed and all of
the yellow–white thickened endocardium removed.
Surgical options are LV endocardiectomy, AV valve
repair or replacement
Exclusion of fibrotic RV in a pure RVEMF by a BDG
connection (JaganMohan Tharakan SCTIMST et.,al)
98. BDG shunt is offered only to patients with isolated
RVEMF, with no pulmonary hypertension, mitral
incompetence or diastolic dysfunction.
Any grade of LVEMF is considered a contraindication
for BDG shunt.
99. Because the myocardium is not usually affected, the severe hemodynamic
derangement associated with EMF is relieved with successful resection of
the endocardium.
Depending on the location of the disease (right or left ventricle, apex or
inflow tract), a transapical or transventricular approach can be used.
Common postoperative complications include low cardiac output, heart
block, and ventricular arrhythmias.
100. The rationale for surgery has been the following.
Poor prognosis in the long term with medical treatment
in class III and IV patients (surgery offers 5 year survival of 65–
75%; 10 year survival10 of 60–70%
Hemodynamic derangement is due to restriction and
AV valve incompetence (correctable by endocardiectomy
and AV valve repair or replacement).
Rarity of myocardial involvement by fibrosis.
Rarity of recurrence of same fibrotic process after
endocardiectomy.
102. Lepley first operated successfully on advanced EMF by
performing endocardial decortication and mitral valve
replacement (MVR) through an apical ventriculotomy .
This has subsequently been adapted effectively for right
sided disease. With 5-year survival of 72% achievable even
amongst end-stage sufferers, surgery represents the only
hope of prolonging survival in this incurable disease .
103. Keys to long-term success include thorough
decortication and bioprosthetic valve replacement :
xenografts constitute the bulk of reported experience
whilst death from late thrombosis of a mechanical
prosthesis has occurred
Despite considerable surgical experience with
managing the chronic fibrotic stages in LEM, the
clinicopathological behaviour and perioperative
course in the acute thrombotic stage remains a
mystery.
104. Mitral valve repair (MVr) has been described for
advanced EMF but not in the acute stages
Early postoperative recurrence of suggests
that MVR may be more appropriate.
Rapid disease recurrence jeopardizing a
conserved mitral valve in acute eosinophilic
endomyocarditis cautions against surgical repair
despite its many advantages.
A bioprosthesis is associated with reduced
thrombotic complications and may be the
treatment of choice for this rare pathology.
105. Hassan, W. M. et al. Chest 2005;128:3985-3992
Left ventricular angiogram in the right anterior oblique view showing a small left
ventricle with apical obliteration, severe MR, and dilated left atrium in a patient
with left-sided EMF (top, a) and after surgery with endocardectomy and mitral
valve replacement (bottom, b)
Figure 6. Histology of the LA demonstrates marked fibrotic thickening of the endocardium (arrow), with proliferation of fibrous tissue in the underlying myocardium, which is consistent with endomyocardial fibrosis (Masson trichrome stain, original magnification ×50).
Figure 5. At autopsy, the left ventricular apex was obliterated by prominent trabeculations and fibrosis (mushroom sign; arrows).
Figure 4. Delayed-enhancement MRI of left ventricle radial view demonstrates subendocardial hyperenhancement of the apex of the left ventricle, suggesting fibrosis (arrows). Abbreviations as in Figure 2.
