Cardiomyopathies are diseases of the heart muscle that cause mechanical and electrical dysfunction. They can be genetic or acquired from other systemic diseases. The main types are dilated, hypertrophic, and restrictive cardiomyopathy. Dilated cardiomyopathy is characterized by ventricular dilation and impaired contraction, while hypertrophic cardiomyopathy causes thickened heart walls. Restrictive cardiomyopathy decreases ventricular filling. Causes include genetic mutations, viral infection, alcohol toxicity, iron overload, and amyloidosis. Classification systems have multiple overlapping categories due to the heterogeneous nature of cardiomyopathies.

1. CARDIOMYOPATHY
Dr Nandakanta Mahanta
PGT
Moderators
Dr S. A. Sheikh
Dr R Biswas

2. Definition
“ Cardiomyopathies are a heterogeneous group of diseases of the
myocardium associated with mechanical and/or electrical
dysfunction that usually (but not invariably) exhibit
inappropriate ventricular hypertrophy or dilatation and are due
to a variety of causes that frequently are genetic.
Cardiomyopathies either are confined to the heart or are part
of generalized systemic disorders, often leading to
cardiovascular death or progressive heart failure-related
disability.”

3. Manifest as :
i) failure of myocardial performance:: mechanical (e.g.,
diastolic or systolic dysfunction) >> CHF
or
ii) life-threatening arrhythmias

4. Primary cardiomyopathies
i)genetic
ii) acquired diseases of myocardium,
Secondary cardiomyopathies
myocardial involvement as a component of a
systemic or multiorgan disorder.

5. Cardiomyopathies can be classified according to a variety
of criteria, including the underlying genetic basis of
dysfunction

6. WHO Classification
• Unknown cause
(primary)
– Dilated
– Hypertrophic
– Restrictive
– unclassified
• Specific heart muscle
disease (secondary)
– Infective
– Metabolic
– Systemic disease
– Heredofamilial
– Sensitivity
– Toxic

7. AHA classification ( 2006)
PRIMARY CARDIOMYOPATHY
GENETIC
MIXED
ACQUIRED
HCM
ARVC/D
LVNC
STORAGE
DISESE
CONDUCTION DEFECT
DCM
RESTRICTIVE
Non hypertrophic
Non dilated
Inflammatory
( myocarditis)
Stress provoked
tako
peripertum
Infant of
IDDM

8. Three pathologic patterns
 Dilated cardiomyopathy (including arrhythmogenic right
ventricular cardiomyopathy) (90% of cases),
 Hypertrophic cardiomyopathy
 Restrictive cardiomyopathy (least frequent)

10. Dilated Cardiomyopathy
• characterized morphologically and functionally by
progressive cardiac dilation and contractile (systolic)
dysfunction, usually with concomitant hypertrophy.
• primary and secondary

11. 1. Genetic Influence
• mutations in TTN, a gene that encodes titin (it is the largest
protein expressed in humans) :: 20 %
• autosomal dominant :: predominant pattern
• X-linked , autosomal recessive and mitochondrial
inheritance

12. • Mitochondrial inheritence : pediatric population
– deletions in mitochondrial genes :: defects in oxidative
phosphorylation;
– mutations in genes enncoding enzymes involved in ß-oxidation of
fatty acids
• X linked (puberty and into early adulthood) :: mutations
affecting the membrane-associated dystrophin protein that
couples cytoskeleton to the extracellular matrix
• congenital abnormalities of conduction

13. 2. Myocarditis
viral myocarditis :
coxsackie B and other viruses within
myocardium of patients with DCM

14. 3. Alcohol and other toxins
• Alcohol or its metabolites (acetaldehyde) => direct toxic
effect on the myocardium.
• morphologic features do not distinguish alcoholic
cardiomyopathy from DCM of other causes
• doxorubicin (Adriamycin)
• targeted cancer therapeutics (e.g., tyrosine kinase
inhibitors).
• Cobalt :: heavy metal :: cardiotoxicity :: beer production

15. 4. Peripartum cardiomyopathy
• late in pregnancy or up to months
• Mechanism :: poorly understood
• Suggested primary defect :: microvascular angiogenic
imbalance within the myocardium => functional ischemic
injury postpartum.

16. 5. Iron overload
• Hereditary hemochromatosis / multiple
transfusion
• DCM : MC manifestation

17. 6. Supraphysiologic stress
• persistent tachycardia, hyperthyroidism, in the fetuses of
insulin Dependent diabetic mothers
• Pheochromocytoma :: Excess catecholamines=> multifocal
myocardial contraction band necrosis=> DCM
• cocaine / vasopressor agents such as dopamine
• takotsubo cardiomyopathy ::
• direct myocyte toxicity due to calcium overload or to focal
vasoconstriction in the coronary arterial macro- or
microcirculation

18. Morphology

19. C/F
• 20 and 50 yrs
• dyspnea, easy fatigability, and poor exertional
capacity.
• At the end stage, ejection fractions :: << 25%
• (normal = 50% to 65%)
• Sudden death d/t progressive cardiac failure
or arrythmia

20. Arrhythmogenic Right Ventricular
Cardiomyopathy
• inherited disease of myocardium
• right ventricular failure and rhythm disturbances
(particularly ventricular tachycardia or fibrillation) +
sudden death

21. Morphology
• the right ventricular wall is severely thinned due to loss
of myocytes, accompanied by extensive fatty infiltration
and fibrosis.
• autosomal dominant
• defective cell adhesion proteins in the desmosomes that
link adjacent cardiac myocytes.

23. Hypertrophic Cardiomyopathy
• Incidence:: 1 in 500
• clinically heterogeneous, genetic disorder
• characterized by::
– myocardial hypertrophy, poorly compliant left ventricular
myocardium leading to abnormal diastolic filling, and
– intermittent ventricular outflow obstruction ( 1/3RD cases)
• thick-walled, heavy, and hypercontracting heart
• Diastolic dysfunction

24. Pathogenesis
• 100% cause :: genetic
• autosomal dominant
• mutations in the genes that encode sarcomeric proteins
• ß-myosin heavy chain (ß -MHC) MC
• Cardiac TnT, α-tropomyosin, MBP-C

25. PATHOGENESIS
100% genetic cause
defect in sarcomeric protein
Defect in energy transfer from
mitochondria to sarcomere &/or direct
sarcomeric dysfunction
HCM
● hypertrophy, marked
● asymmetrical septal
hypertrophy
● myofibril disarray
● fibrosis
● LV outflow tract
plaque
Mutation involving β
Myosin heavy chain

26. • Sarcomeric alteration >> abnormal cardiac
contraction causing a secondary compensatory
hypertrophy
• Defective energy transfer from its source of generation
(mitochondria ) >> its site of use (sarcomere)
• Interstitial fibrosis :: secondary to exaggerated response of
myocardial fibroblasts to the primary myocardial
dysfunction.

27. Morphology
• the heart is thick walled, heavy, hyper contracting
• Massive myocardial hypertrophy ; without ventricular
dilatation.
• Asymmetric septal hypertrophy
• on cross section, ventricular cavity loses round to ovoid
shape & becomes banana shaped

28. Histological features:
• Massive myocyte hypertrophy
• transverse myocyte diameter > 40 micron
• Myocyte disarray
• interstitial & replacement fibrosis

30. Endocardial thickening & perivascular collagen fibrosis

31. C/F
• Reduced stroke volume due to impaired diastolic filling
• AF
• Mural thrombus formation, embolization
• Stroke
• Cardiac failure
• Ventricular arrythmia
• sudden unexplained death of young athletes.

32. Restrictive cardiomyopathy
• Characterised by :
primary decrease in the ventricular
compliance, resulting in impaired ventricular
filling during diastole

33. • Primary / idiopathic
• Secondary / radiation fibrosis, sarcoidosis , amyloidosis,
metastatic tumor, inborn errors of metabolism

34. Morphology
• Not distinctive
• Ventricles : N / ↑
• Myocardium: firm, non compliant
• Biatrial dilatation
• Microscopically :: interstitial fibrosis : patchy / diffuse
• Endomyocardial biopsy : specific etiology

35. FUNCTIONAL
PATTERN
LEFT
VENTRICULAR
EJECTION
FRACTION
MECHANISM
OF HEART
FAILURE
CAUSES OF
PHENOTYPE
DILATED < 40 % Impairment of
contractility
(systolic)
mixed
HYPERTROPHIC 50 – 80 % Impairment of
compliance
(diastolic)
genetic
RESTRICTIVE 45- 90 % Impairment of
compliance
(diastolic)
Idiopathic/
secondary

36. Other restrictive conditions :
• Endomyocardial fibrosis :: fibrosis of the ventricular
endocardium , subendocardium
• Loeffler endomyocarditis :: endomyocardial fibrosis,
mural thrombi, peripheral eosinophilia , eosinophilic
infiltrate in multiple organs
• Endocardial fibroelastosis : fibroelastic thickening of left
ventricular endocardium, aortic vulve obstruction and
congenital cardiac anolmalies

37. SECONDARY CARDIOMYOPATHY
Disorder that shows pathological myocardial involvement as a
part of generalized ( multiorgan ) disorder.
This group includes :
- infiltrative disorder
- storage disorder
- drugs
- radiation

38. AMYLOIDOSIS
4 types of amyloidosis are associated with cardiac symptoms
a) immunoglobin associated(AL)
b) familial (ATTR)
c) systemic senile
d) secondary (AA)

39. rubbery tissue with brown gray color
ventricle
CUT SURFACE-WAXY
Thick walled, small
chamber
HCM
Thin walled mimicking
DCM
MICROSCOPIC
 interstitial & perimyocytic deposition of amyloid in cast like manner
 attenuated myocyte

41. FABRY DISEASE
• x linked
• α galactosidase A deficiency
• glycophospholipid accumulation in myocytes
• marked LV hypertrophy ( similar to HCM)
• myocytes & endothelial cells are diffusely vacuolated
• diagnosis is confirmed by presence of membrane bound
electron dense lamellar myelin ( zebra) bodies.

43. HEMOCHROMATOSIS
• prevalence 1:200 to 1:400
• AR
• ↑iron absorption
• iron deposition in myocytes leads to CHF, conduction defect.
• systolic pump failure causing DCM most common pattern
•
• iron is deposited in myocytes throughout the myocardium
• iron deposits are typically Perinucleur in Prussian blue

44. 4 chamber dilatation

45. ANTHRACYCLINE TOXICITY
• causes direct myocardial injury
• dose dependent :: > 500 mg/m2
• DCM & heart failure
• acute & chronic toxicity
• Toxicity due to
• - lipid peroxidation of myocytes
• - alteration of ca channel
• - oxygen free radical mediated damage

46. Chronic toxicity
toludine blue
Acute toxicity

47. • As per AHA document, formal classifications of heart muscle diseases have proved to be
exceedingly complex and, in many respects, contradictory. Indeed, given the
heterogeneous nature of the cardiomyopathies, there probably is no single classification
that can be regarded as generally acceptable to all interested parties from diverse
disciplines, including clinical and research physicians, scientists.
• chronic myocardial dysfunction secondary to ischemia, valvular abnormalities, or
hypertension can cause significant ventricular dysfunction; these conditions should not be
denoted as cardiomyopathies.
CONCLUSIONS