This document discusses endomyocardial biopsy and cardiomyopathy. It describes endomyocardial biopsy as a technique to sample heart tissue for diagnosis of cardiac disorders. Key indications include diagnosing myocarditis, transplant rejection, and cardiomyopathies. Complications can include perforation and arrhythmias. The document also defines and classifies different types of cardiomyopathy such as dilated, hypertrophic, and restrictive cardiomyopathy. It provides details on clinical features, morphology, causes, and pathology of these conditions.

1. Endomyocardial biopsy and
cardiomyopathy
Presenter : Dr Suma H V
Moderator : Dr S Shivakumar

2. Contents
• Endomyocardial biopsy
– Introduction
– History
– Indications
– Instruments
– Procedure
– Complications

3. • Cardiomyopathy
– Definition
– Classification
– Morphology
• References

4. Endomyocardial biopsy

5. Introduction
• Technique by which heart tissue is sampled
from the patients with suspected cardiac
disorders for microscopic evaluation and
diagnosis of the lesions.
• Gold standard mode of investigation for
diagnosing cardiac diseases.

6. Historical aspects
• Open surgical biopsies of heart - 1950’s
Using Vim-silverman’s needle through
thoracotomy / trans-thoracic approach.
• 1st trans-venous biopsy –Bioptome in Japan in
1962

7. • Modified bioptome- CAVES-SCHULTZ-
STANFORD bioptome – Stanford -1972

9. Indications
• To diagnosis
– Myocarditis
– Transplant rejection
– cardiomyopathies
• To evaluate
– Drug toxicity (anthracycline, doxorubicin)
– Unexplained CCF

10. Instruments
• Flexible bioptomes
• Commonly used bioptomes are:
– Novatome- single use 50cm
– Argon forceps
– Bipal bioptome
• Fluoroscopy is the imaging modality

12. Patient preparation
• Routine lab tests
• ECG
• Chest x-ray.
• Nil per oral for 6hrs.
• Cardiac Catheterization lab.

13. Procedure
• Performed through the transvascular
approach
• Right ventricle is preferred
-Easier and safer to biopsy
-Representative site in diffuse diseases.
• Left ventricle is preferred in sarcoidosis and
done via arterial approach

14. • A flexible, plastic tube called a “sheath” is
inserted into the vein in the neck or groin
• Insertion of “pulmonary artery catheter” into
the right side of heart
• Catheter is removed.

15. • Bioptome is guided through the sheath into
the heart.
• Biopsy forceps can easily be taken upto the
apical portion of Right ventricular septum.
• 3-4 tissue samples of 2-3 mm size are
obtained.
• Then the bioptome and sheath are removed.

16. • Flexible, disposable bioptomes- presently
available.
• Availability of catheters and bioptome forceps
of different sizes and designs
• Apical curvature- for easy sampling and grip
on the tissue.

18. Procedure

19. Tissue Processing
• 4-5 biopsy fragments are processed routinely
and 1 fragment for EM exam.
• Transplant biopsies- if vascular rejection is
suspected, 1 fragment is frozen for
immunofluorescence.
• Anthracycline, Chloroquine and Amiodarone
toxicity- All fragments are processed for EM.

20. PROBLEMS DURING INTERPRETATION
• Sampling error-due to focal nature of disease
• Crush artifacts
• Contraction bands
• Focal interstitial fibrosis

21. PROBLEMS DURING INTERPRETATION
cont….
• Interstitial mesenchymal cells closely resemble
lymphocytes.
• Endocardial thickening
• Adipose tissue

22. Complications
• PERFORATION
– Chest pain and pericardial effusion as judged by
transthoracic echocardiography or TEE
• The risk of perforation can be reduced by
using a specially curved sheath to guide the
biopsy forceps toward the interventricular
septum.

23. • Air embolism
• Myocardial infarction
• Transmission of infections
• Damage to valves
• Chest pain, hematoma
• Arrythmias(AF/VF)
• Pneumothorax
• Haemopericardium

24. Cardiac transplantation
• Worldwide about 1 lakh adult and 11000
pediatric heart transplantation have been
performed
• Survival rate is 88% at 1st year,
80% at 2nd year
75% at 3rd year

25. Grading of transplant rejection

28. CARDIOMYOPATHY

29. Introduction
• Heterogeneous group of diseases
• Mechanical &/or electrical dysfunction
• Ventricular hypertrophy or dilatation
• Variety of causes that frequently are genetic.
• Cardiomyopathies either are confined to the
heart or are a part of generalized systemic
disorders

30. Functional classification
• Dilated cardiomyopathy
• Hypertrophic cardiomyopathy
• Restrictive cardiomyopathy
• Arrhthymogenic Right Ventricular
disease(ARVD)

31. Morphological classification of
cardiomyopathies
• Primary cardiomyopathies
– Dilated cardiomyopathy
– Hypertrophic cardiomyopathy
– Restrictive cardiomyopathy
– RV arrhythmogenic cardiomyopathy
• Inflammatory cardiomyopathy / myocarditis

32. • Secondary cardiomyopathy
– Infiltrative
– Storage disorder
– Toxic/ drug related
– Peripartal cardiomyopathy

33. Dilated cardiomyopathy

34. Definition
• Primary cardiomyopathy that principally
affects the myocardium leading to LV dilation
and systolic dysfunction.

35. Incidence and prognosis
• Prevalence – 36/1,00,000
• 3rd most common cause of heart failure
• Most frequent cause of heart transplantation
• Complete recovery is rare
• 50% die within 2yrs

36. Causes
• Genetic
– Autosomal dominant
– Mutations in genes encoding dystrophin,δ
sarcoglycan, troponin T, β MHC etc
• Myocarditis
• Alcohol and other toxins
• Childbirth (peripartum cardiomyopathy)

37. Clinical features
• Peak incidence in middle age
• Symptoms may be gradual in onset
• Acute presentation
– Misdiagnosed as viral URI in young adults

38. • Symptoms/Signs of heart failure
– Pulmonary congestion (left heart failure), dyspnea,
orthopnea
– Systemic congestion (right heart failure), edema,
nausea, abdominal pain, nocturia
– Low cardiac output
– Hypotension, tachycardia, tachypnea
– Fatigue and weakness
• Arrhythmia
– Atrial fibrillation, conduction delays, sudden death

40. Morphology
• Heart enlarged, heavy, flabby
• Mural thrombi
• Dilatation of all chambers, both ventricular
hypertrophy

42. Microscopy
• Hypertrophic myocardial fibres
• Cardiac myocytes show degenerative changes
• Interstitial and endocardial fibrosis

43. Peripartum cardiomyopathy
• Four criteria: three clinical and one echocardiographic
1. Development of heart failure during last trimester
of pregnancy or first six months post partum.
2. Absence of any identifiable cause for cardiac failure.
3. Absence of any recognizable heart disease prior to
last trimester of pregnancy.

44. 4. Echocardiographic criteria - Demonstrable
proof of left ventricular systolic dysfunction.
- Ejection fraction less than 45%,
-Left ventricular end- diastolic dimension
>2.7cm/m square of body surface area.

45. Hypertrophic cardiomyopathy

46. • Most common genetic disorder of heart
• Prevalence : 1 in 500 adults
• Characterised by myocyte hypertrophy in the
absence of hypertension, stenotic valvular
disorder or infiltrative disorders

47. Pathogenesis
• Autosomal dominant
• Remaining are sporadic
• Mutations are mostly missense
• Mutations causing HCM found in genes
encoding β MHC, cardiac TnT, α tropomyosin,
myosin binding protein C

48. Pathophysiology
• Impaired diastolic filling
↓
reduced stroke volume
• Reduced CO and increase in pulmonary
venous pressure
↓
exertional dyspneoa

49. Clinical features
• Asymptomatic
• Symptomatic
– Dyspnea
– Chest pain
– Fatigue, pre-syncope, syncope
– Palpitation, PND, CHF, dizziness

51. • Begins during early
adolescence and stops
when growth has
finished
• Left ventricle almost
always affected.
• Hypertrophy is usually
greatest in the septum

52. • Asymmetric septal
hypertrophy with obstruction
to the outflow of blood from
the heart may occur. The
mitral valve touches the
septum, blocking the outflow
tract. Some blood is leaking
back through the mitral valve
causing mitral regurgitation

54. Mimicking Hypertrophic
Cardiomyopathy
• Cardiac amyloidosis
• Athlete's heart
• Fabry disease
• Apical hypertrophy - apical cavity obliteration
caused by hypereosinophilic syndrome

55. Athlete's Heart Vs Hypertrophic
Cardiomyopathy HCM
HCM
• Can be asymmetric
• Wall thickness: > 15 mm
• LA: > 40 mm
• Diastolic function:
always abnormal
Athletic heart
• Concentric & regresses
• < 15 mm
• < 40 mm
• Normal

56. Restrictive cardiomyopathy

57. Introduction
• Rigid ventricular wall with impaired
ventricular filling
• Contractile functions are normal
• Abnormal diastolic function
• Less common

58. CAUSES
• Primaryidiopathic
• Secondary associated with
– Radiation fibrosis
– Amyloidosis
– Sarcoidosis
– Metastatic tumors
– Metabolic deposition diseases

59. Clinical manifestations
• Symptoms of right and left heart failure
• Echo-Doppler – Abnormal mitral inflow
pattern -Prominent E wave (rapid diastolic
filling)
• Almost invariably progresses to congestive
heart failure,10% survive for 10 yrs

60. Morphology
• Ventricles are of normal size
• Cavities are not dilated
• Myocardium is firm and non compliant
• Biatrial dilatation is common
• Patchy/diffuse interstitial fibrosis

63. Arrhythmogenic right ventricular
cardiomyopathy
• Inherited disease of cardiac muscle
• RVF, rhytm disturbances, ventricular
tachycardia, fibrillation
• Right ventricular wall is thinned, extensive
fatty infiltration and fibrosis
• Autosomal dominant inheritence

64. Secondary cardiomyopathies

65. Cardiac Amyloidosis
• Deposition of abnormal protein amyloid
• Characterised by :congestive heart failure
myocardial dysfunction

66. Types
1. Immunoglobulin associated amyloidosis
2. Familial/heriditary amyloidosis
3. Senile amyloidosis

67. Morphology
• Ventricles - Normal to dilated
- thinned walls (DCM)
- thickened LV walls with small
chambers (HCM)
• Cut surface – waxy appearance
• Can also involve endocardium, myocardium,
pericardium, valves and vessels

69. Pompe disease
• - deficiency of acid maltase
- Autosomal recessive
-hepatomegaly, failure to thrive, hypotonia,
macroglossia, massive cardiomegaly
- heart is enlarged and mimics HCM

71. Fabry’s disease
• Storage disorder
• Deficiency of alpha galactosidase A enzyme
↓
Glycophospholipid accumulation
• X – linked disorder
• Ventricular hypertrophy, heart failure,
arrhythmia, conduction defects

73. Hemochromatosis
• Mc inheritable metabolic disorder
• Prevalence 1:200-400
• Increased iron deposition in heart, liver, pituitary
gland, pancreas and skin.
• Autosomal recessive
• HFE- mc mutation

75. Drug related cardiomyopathy
• Anthracyclin antibiotics- doxorubicin,
daunorubicin
• Precipitated by infection, pregnancy or
surgery
• Congestive heart failure, arrhythmia –
common

76. Microscopy
• Tissue is fixed and processed in glutaraldehyde
solution
• 10 plastic blocks is required for assessing
numerical grade
• One micron sections are cut and stained by
toluidine blue stain and assessed under light
microscopy for distribution and extent of cell
injury

77. • Myocytes appear shrunken with homogenous pale
cytoplasm and cytoplasmic vacuolization

78. Electron microscope
• Myofibrillary loss
• Partial/complete loss of fibrils

79. Grading of chronic anthracycline
cardiotoxicity
• Grade 0 – normal ultrastructural appearance
of myocytes
• Grade 1.0 – isolated or scattered myocytes
showing sarcotubular distension or early
myofibrillar loss; damage to <5% of all cells
• Grade 1.5 – changes as grade 1 but involving
6%-15% of all cells

80. • Grade 2 – clusters of myocytes with
myofibrillary loss or sarcotubular distension
involving 16-25% of all cells
• Grade 2.5 – numerous damaged myocytes
(26-35%) showing characterised changes
• Grade 3 – diffuse/confluent myocyte damage
of >35% of cells, necrotic cells may be seen

81. Inflammatory cardiopathy
(Myocarditis)
• Definition:
Myocardial process characterized by the
presence of both an inflammatory infiltrate
and myocyte damage or necrosis not typical of
the myocardial damage of ischemic heart
disease.

82. Etiology
• Idiopathic myocarditis
• Drug induced
• Myocarditis associated with systemic disease
• Sarcoidosis
• Idiopathic giant cell myocarditis

83. Myocarditis
• Both inflammation and myocyte damage are
present.
• Depending on the composition of the cellular
infiltrate the specific type of myocarditis.

85. Drug- related myocarditis
• Hypersensitivity myocarditis
• Toxic myocarditis
• Drug-induced cardiomyopathy (e.g.,
anthracycline, chloroquine)
• Giant cell myocarditis

86. Hypersensitivity Myocarditis
• Most common form of acute drug-related
myocardial injury
• Antibiotics, diuretics, and antihypertensive
drugs
• Clinical signs : rash, fever, peripheral
eosinophilia, and occasionally arrhythmias,
sudden death, and congestive heart failure.

87. • The histopathologic features include uniform
lesions distributed in the subendocardial,
perivascular, and interstitial tissues between
bundles of myocytes.

89. Toxic Myocarditis
• Uncommon
• Characterized by direct myocyte cytotoxicity.
• Causative agents - antineoplastic drugs
• The lesions are focal and temporally
heterogeneous.

91. Sarcoidosis
• Cardiac involvement in sarcoidosis is 25% to
60%.
• Include classic noncaseating granulomatous
inflammation, lymphocytic myocarditis, DCM
and normal myocardium.
• Diffuse myocardial involvement progresses to
myocyte hypertrophy and interstitial fibrosis
resembling DCM

92. Gross
• Firm, white nodules
forming discrete masses
within the
interventricular septum,
LV free wall, or papillary
muscle

94. Idiopathic giant cell myocarditis
• Rare
• Fatal form of myocarditis that occurs in
previously healthy young adults.
• Clinical onset is abrupt
• Characterized by rapidly progressive heart
failure and/or arrhythmias.

95. Morphology
• Multifocal areas of necrosis are easily
observed in the heart.
• The heart weight is normal or slightly
increased. All chambers of the heart are
uniformly involved in most cases.

97. Conclusion
• Endomyocaedial biopsy is helpful is diagnosing
many cardiac disorders

98. References
• Sternberg, s diagnostic surgical pathology.
• Silverberg’s principle and practice of surgical
pathology and cytopathology.
• Cardiovascular pathology
• Journals on cardiovascular pathology

99. Thank you