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1. dilated
CARDIOMYOPATHIES

2. Definition
 Cardiomyopathies are defined as
"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."

3. WHO Classification
anatomy & physiology of the LV
1. Dilated
• Enlarged
• Systolic dysfunction
2. Hypertrophic
• Thickened
• Diastolic dysfunction
3. Restrictive
• Diastolic dysfunction
3. Arrhythmogenic RV dysplasia
• Fibrofatty replacement
3. Unclassified
• Fibroelastosis
• LV noncompaction

4. Dilated Cardiomyopathy
•An enlarged left ventricle with decreased systolic function
as measured by left ventricular ejection fraction
characterizes dilated cardiomyopathy .
• Systolic failure is more marked
• Diastolic dysfunction, in the setting of marked volume
overload

5. MajorCauses of Dilated
Cardiomyopathy
 Inflammatory Myocarditis –
Infective/Noninfective
 Toxic
 Metabolic
 Inherited Metabolic Pathway Defects
 Familial
 Idiopathic
 Miscellaneous

6. Pathophysiology
 Brief primary injury such as infection or toxin exposure.
 Some myocytes may die during the initial injury, while
others survive only to have later programmed cell death,
(apoptosis).
 As the surviving myocytes hypertrophy to accommodate
the increased burden of wall stress,
 Local and circulating factors stimulate deleterious
responses that contribute to progression of disease,
even in the absence of further primary injury,Dynamic
remodeling and the amount of ventricular dilation.
 Mitral regurgitation commonly develops as the valvular
apparatus is distorted by ventricular dilation

8. DCM: Inflammatory
Infective
Reported with almost all types of infectious agents
 Viral- Co xsackie , adenovirus, HIV, hepatitis C
 Parasitic - T. cruzi— Chag as' dise ase , toxoplasmosis
 Bacterial- diphtheria, Spirochetal ,Bo re llia
 Rickettsial-Q fever
 Fungal -with systemic infection

9. DCM: Inflammatory
Noninfective
 Granulomatous inflammatory disease -Sarcoidosis
,Giant cell myocarditis
 Hypersensitivity myocarditis
 Polymyositis,
 Dermatomyositis
 Collagen vascular disease
 Peripartum cardiomyopathy
 Transplant rejection

10. DCM: Inflammatory
 Mechanism
 Direct tissue injury resulting from viral infection
 Immune mediated injury
 Viral infection in susceptible hosts may be a
proximate cause of cardiomyopathy

11. DCM: Peripartum
Diagnostic Criteria
 1 mo pre, 6 mos post
 Echo: LV dysfunction
 LVEF < 45%
 LVEDD > 2.7 cm/m2
Epidemiology/Etiology
 1:4000 women
Riskfactors - increased maternal age, increased
parity, twin pregnancy, malnutrition, use of
tocolytic therapy for premature labor, and
preeclampsia or toxemia of pregnancyJAMA

12. DCM: Peripartum
Proposed mechanisms:
 Inflammation - reflect increased susceptibility
to viral myocarditis or
 Autoimmune -myocarditis due to cross-
reactivity of anti-uterine antibodies against
cardiac muscle.
 prolactin cleavage fragment, salt ingestion
 Women with full recovery are more likely to
tolerate a subsequent pregnancy than are

13. DCM: Toxic
 Alcohol
 Catecholamines: amphetamines, cocaine
 Chemotherapeutic agents: (anthracyclines, trastuzumab)
 Interferon
 Other therapeutic agents (hydroxychloroquine, chloroquine)
 Drugs of misuse (emetine, anabolic steroids)
 Heavy metals: lead, mercury
 Occupational exposure: hydrocarbons, arsenicals

14. DCM: Toxic
Alcoholic cardiomyopathy
 Toxicity is attributed both to alcohol and acetaldehyde.
 Superimposed vitamin deficiencies and toxic a additives
are rarely implicated.
 6 drinks daily for 5–10 years, but frequent binge
drinking may also be sufficient.
 Reversible with abstinence
 Mechanism?:
 Myocyte cell death and fibrosis
 Directly inhibits: mitochondrial oxidative
phosphorylation Fatty acid oxidation

15. DCM: Toxic
Anthracyclines
 Cause vacuolar degeneration and myofibrillar loss.
 Generation of reactive oxygen species involving heme
compounds is currently the favored explanation for myocyte
injury and fibrosis.
 Disruption of the large titin protein may contribute to loss of
sarcomere organization.
 Three different presentations
 Acute heart failure/ Early onset /The chronic presentation -
 Leads to a relatively nondilated ventricle, perhaps due to
fibrosis.
 Thus, the stroke volume may be severely reduced with an
ejection fraction of 30–40%,
 Therapy is suppression of "inappropriate" sinus tachycardia,
and attention to postural hypotension .

16. DCM: Metabolic
 Nutritional deficiencies: thiamine, selenium,
carnitine
 Electrolyte deficiencies: calcium, phosphate,
magnesium
 Endocrinopathy:
 Thyroid disease
 Pheochromocytoma
 Diabetes
 Obesity
 Hemochromatosis

17. DCM :Familial
 Skeletal and cardiac myopathy
 Dystrophin-related dystrophy (Duchenne's,
Becker's)
 Mitochondrial myopathies (e.g., Kearns-Sayre
syndrome)
 Arrhythmogenic ventricular dysplasia
 Hemochromatosis
 Associated with other systemic diseases

18. DCM :Familial
 30% of ‘idiopathic’
 Inheritance patterns
 Autosommal dom/rec, x-linked, mitochondrial
 Associated phenotypes:
 Skeletal muscle abn, neurologic, auditory
 Mechanism:
 Abnormalities in:
 Energy production
 Contractile force generation
 Specific genes coding for:
 Myosin, actin, dystophin…

19. Inherited Defects in Metabolic Pathways Associated
With Cardiomyopathy
Glycogen Storage Diseases
 II—Pompe's (alpha 1,4
glucosidase)
 III—Forbes: de-branching
enzyme (amylo 1,6 glucosidase)
Glucose Metabolism(Defective
PRKAG2a
 Fatty acid metabolism
 Carnitine transport defect
 Medium chain Acyl-CoA
dehydrogenase
 Long chain Acyl-CoA
dehydrogenase
 Sphingolipidoses
 Fabry's dise ase (alpha
galactosidase A)
 Gaucher disease (beta-
glucocerebroside)
 Disorders of lysosomal function
 Danon's disease—(lysosome-
associated membrane protein,
LAMP2)
 Miscellaneous
 Hemochromatosis—Fe metabolism
 Familial amyloidosis—abnormal
transthyretin
 Barth syndrome—tafazzin defect

20. Overlap with Restrictive
Cardiomyopathy
 "Minimally dilated cardiomyopathy"
 Hemochromatosis
 Amyloidosis
 Hypertrophic cardiomyopathy

21. DCM: Idiopathic
 Is a diagnosis of exclusion,
 when all other known factors have been
excluded.
 two-thirds of dcm are still labeled as
idiopathic;
 may reflect unrecognized genetic disease.
 Continued reconsideration of etiology often
reveals later

22. Miscellaneous
Arrhythmogenic RV Dysplasia
 Desmosomal complex disrupt myocyte junctions
and adhesions,
 Myocardium of RV free wall replaced:
 Fibrofatty tissue
 Regional wall motion/function is reduced
 Ventricular arrhythmias
 SCD in young
 "woolly hair," and thickened palms and soles.

23. Arrhythmogenic RV Dysplasia

24. Miscellaneous
LV Noncompaction
Diagnostic Criteria
 Prominent trabeculations, deep recesses in LV apex
 Thin compact epicardium, thickened endocardium
 associated with multiple genetic variants in the sarcomeric
and other proteins such as tafazzin
Prognosis and Treatment
 Increased risk of CHF, VT/SCD, thrombosis
 Hereditary risk
 Screening of offspring

25. Echo: LV Noncompaction

26. Miscellaneous
Tako-Tsubo Cardiomyopathy
 The apical ballooning syndrome, or stress-induced
cardiomyopathy, occurs typically
 In older women after sudden intense emotional or
physical stress
 Presentations include pulmonary edema, hypotension,
and chest pain with ECG changes mimicking an acute
infarction.
 May result from intense sympathetic activation with
heterogeneity of myocardial autonomic innervation,
diffuse microvascular spasm, and/or direct
catecholamine toxicity.

27. Tako-Tsubo Cardiomyopathy

28. Evaluation of the DCM
HISTORY
 Detailed family history
 History of alcohol, illicit drugs, chemotherapy or radiation
therapy
 A past or associated history of rheumatologic, endocrine, or
infectious diseases
 Assessment of ability to perform routine and desired
activities
 Assessment of volume status, orthostatic blood pressure,
body mass index

29. Physical Exam
Decreased C.O.
Tachycardia
↓ BP and pulse pressure
cool extremities (vasoconstriction)
Pulsus Alternans (end-stage)
Pulmonary venous congestion:
rales
pleural effusions
Cardiac:
laterally displaced PMI
S3
mitral regurgitation murmur
Systemic congestion
↑ JVD
hepatosplenomegaly
ascites
peripheral edema

30. Chemistry
 Serum sodium,
potassium,calcium,magnesiu
m
 Fasting glucose
 Creatinine,blood urea
nitrogen
 Albumin, total protein,
 Liver function tests
 Lipid profile
 Thyroid-stimulating hormone
 Serum iron, transferrin
saturation
Hematology:
 Hemoglobin/hematocrit
 White blood cell count
with differential,including
eosinophils
 Erythrocyte
sedimentation rate

31. SEROLOGY
 Acute viral (coxsackie virus, echovirus,
influenza virus)
 Human immunodeficiency virus,
 Chagas' disease,
 Lyme disease,
 Toxoplasmosis

32. X-RAY CHEST
 Cardiomegaly
 Pulmonary vascular
congestion
 Kerley B lines
 Prominent
vasculature of the
upper lung fields.
 Pleural effusion
usually on the right
side, but it can be
bilateral

33. Electrocardiogram
 No specific electrocardiographic findings
 Sinus tachycardia is often present
 poor R wave progression, intraventricular conduction
delays, and LBBB.
 A wide QRS complex portends a worse prognosis
 left ventricular fibrosis may exhibit anterior Q waves
 nonspecific ST-segment and T wave abnormalities as
well as P wave alterations
 Persistent supraventricular or ventricular
tachyarrhythmias represent an important etiologic factor
for ventricular dysfunction

34. ECHOCARDIOGRAPHY.
 Cornerstone in the evaluation and
management
 LVEDD are usually greater than 60 mm
 Global hypokinesia
 Decreased EF and FS
 Associated ds

35. ECHOCARDIOGRAPHY

36.  CARDIAC MRI AND MULTIDETECTOR CT
 RADIONUCLIDE IMAGING
 INVASIVE EVALUATION INCLUDING
 ENDOMYOCARDIAL BIOPSY.

37. Management
PHARMACOLOGIC ANDDEVICE THERAPY
 Neurohormonal antagonists to prevent
disease progression
 Diuretics to maintain the volume balance are
the therapeutic cornerstone
 Prophylactic implantable cardiac defibrillators
and biventricular pacemakers is indicated in
appropriate patients

38. CRT: Cardiac Resynchronization
Therapy
1. Improved hemodynamics
 Increased CO
 Reduced LV filling
pressures
 Reduced sympathetic
activity
 Increased systolic function
w/o MVO2
2. Reverse LV
remodeling/architecture
 Decreased LVES/ED
volumes
 Increased LVEF
 Circ ’02, JACC ’02, JACC
’02, NEJM’02

39. SURGERY.
 Patients with structural heart ds conditions
corrected
 Left ventricular assist devices- provide
aggressive mechanical support to patients
with advanced decompensated heart failure
EMERGING SPECIFIC THERAPIES
 infections and immunomodulatory agents
 Stem cells for cardiac regeneration and gene

40. Presentation with Symptomatic Cardiomyopathy
Dilated Restrictive Hypertrophic
Ejection fraction
(normal 55%)
Usually <30% 25-50% >60%
LVDD (nor<55 mm) 60 mm >60 mm (may be
decreased)
Often decreased
Left ventricular wall
thickness
Decreased Normal or increased Markedly increased
Atrial size Increased Increased; may be
massive
Increased; related to
abnormal
Valvular
regurgitation
Related to annular
dilation; mitral earlier,
during
decompensation;
tricuspid late stages
Related to endocardial
involvement; frequent
mitral and tricuspid
regurgitation, rarely
severe
Related to valve-
septum interaction;
mitral regurgitation
Common first
symptoms
Exertional intolerance Exertional intolerance,
fluid retention early
Exertional intolerance;
may have chest pain

41. THANKS !