Transcript cardiomyopathies - howMed Lectures

CARDIOMYOPATHIES
• “Heart disease resulting from a primary
abnormality in the myocardium”
Figure 12-35 Pathways of dilated and hypertrophic cardiomyopathy, emphasizing several important concepts. Some forms of dilated cardiomyopathy (others are caused by myocarditis,
alcohol, and other toxic injury or the peripartum state) and virtually all forms of hypertrophic cardiomyopathy are genetic in origin. The genetic causes of dilated cardiomyopathy involve
mutations in any of a wide variety of proteins, predominantly of the cytoskeleton, but also the sarcomere, mitochondria, and nuclear envelope. In contrast, the mutated genes that cause
hypertrophic cardiomyopathy encode proteins of the sarcomere. Although these two forms of cardiomyopathy differ greatly in subcellular basis and morphologic phenotypes, they share a
common pathway of clinical complications.
Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 27 October 2005 05:18 AM)
© 2005 Elsevier
CARDIOMYOPATHIES
Dilated cardiomyopathy:
Progressive cardiac dilation and contractile dysfunction
Hypertrophic cardiomyopathy:
Myocardial hypertrophy and abnormal diastolic
function
Restrictive cadiomyopathy:
Decrease ventricular compliance impaired diastolic
function
DILATED CARDIOMYOPATHY(DCM)
“A
form of cardiomyopathy
characterized by
progressive cardiac
hypertrophy, dilation and
contractile dysfunction.”
DILATED CARDIOMYOPATHIES
(DCM)
Pathogenesis:
Genetics:
• Autosomal Dominant
• Autosomal Reccessive
• X Linked
• Mitochondria gene mutation
Acquired:
• Myocarditis
• Alcohol
• Other toxins
• Child birth
DILATED CARDIOMYOPATHIES
(DCM)
• Progressive cardiac dilation and contractile
dysfunction
• Enlarged, flabby, weight 2-3 times of normal
• Mural thrombi emboli
• Functional regurgitation of mitral/tricuspid valve
• Myocytes: hypertrophied, Nuclei enlarged,
irregular, stretched
• Interstial and endocardial fibrosis
CLINICAL FEATURES – DCM
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Commonly affects 20 to 60 years old
Slowly progressive CHF
Less ejection fraction
Death due to arrhythmia, cardiac failure
Embolization
DILATED CARDIOMYOPATHIES
(DCM)
Prognosis:
• 50% death- 2 years
• 25% death- 5 years
• Some improvement with therapy
• Transplantation frequently done
CARDIOMYOPATHIES
Arrythmogenic right ventricle
cardiomyopathy
Transmural replacement by fat and
fibrosis
HYPERTROPHIC
CARDIOMYOPATHY (HCM)
• “It is characterized by myocardial
hypertrophy, abnormal diastolic filling and
in about 1/3 cases intermittent left
ventricular outflow obstruction”.
HYPERTROPHIC
CARDIOMYOPATHY (HCM)
Etiology:
Genetic:100% AD
• Missence mutation
• Alpha heavy chain myosin
• Alpha Tropomyosin
• MYBP- C (myosin body protien)
Stroke volume: decreased
HYPERTROPHIC
CARDIOMYOPATHY (HCM)
Gross: Hypertrophy outflow tract
obstruction
Microscopy:
• Myocytes hypertrophy
• Septal hypertrophy
• Interstial fibrosis
• Thickened septal vessels
• Transvers diameter 40um(15um)
CARDIOMYOPATHIES
Restrictive Cardiomyopathy
Decrease in ventricular complianceImpaired filling
Endomyocardial fibrosis
Loeffler endomyocarditis
Endomyocardial fibroelastosis
CARDIOMYOPATHIES
Restrictive Cardiomyopathy
Decrease in ventricular complianceImpaired filling
Endomyocardial fibrosis- Children,
Africa, Tropical countries
Vent- endocardium, sub endocardium
fibrosis- mitral, tricuspid valves
Mural thrombi
CARDIOMYOPATHIES
Restrictive Cardiomyopathy
Loeffler endomyocarditisEndomyocardial fibrosis, mural thrombi
Peripheral eosinophilia
Toxin- eosinophils
Myeloproliferative disorders
Rearrangement- PDGFRA alpha, PDGFRA
beta
Restrictive Cardiomyopathy
Endocardial fibroelastosis
• Uncommon
• 2 years
• Left ventricle: Fibroelastic thickening of
endocardium
• Aortic valve obstruction or other cardiac
anomalies
• Cardiac decompensation death
RESTRICTIVECARDIOMYOPA
THY (RCM)
• Reduced chamber size and stroke
volume
• Impaired diastolic filling
• Exertional dyspnoea
• Anginal pain
• Atrial fibrillation
• Ventricular arrhythmia
• Sudden death
RESTRICTIVECARDIOMYOPATH
Y (RCM)
Etiology:
Idiopathic,Radiation fibrosis,Amyloidosis,
Sarcoidosis, Metastatic tumours
Metabolic diseases- inborn error of metabolism
Morphology:
Ventricles: enlarged, cavities not dilated,
Myocardium: firm, non compliant,
I/S fibrosis, Amyloidosis
TUMOURS OF THE HEART
• PRIMARY ( RARE)
– Myxoma, Rhabdomyoma, Fibroma,
Lipoma, Papillary Fibroelastoma,
Angiosarcoma, Other Sarcomas
• METASTATIC (5% Cancerous patients)
CARDIAC MYXOMA
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Most common primary tumour
Atria (90%) - Fossa ovalis
Mostly single (<1 cm-10 cm)
Hard to soft gelatinous mass
Myxoma cells, EC, Smooth
Muscle & undiff. Cells
• Hamartoma / thrombus?
CARDIAC MYXOMA - (contd)
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Mobile, wrecking - ball effect
Ball - valve obstruction
Embolization
Constitutional symptoms due to IL-6
Surgical removal - curative
Familial cardia myxoma (10%)
CARDIAC RHABDOMYOMA
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Most common - infants & children
Obstruction - valve / chamber
Grayish-white mass
Spider cells, large rounded cells.
CARDIAC LIPOMA
• Subendocardium, myocardium or
subpericardium.
• LV, right atrium or atrial septum
• Asymptomatic
• Ball - valve obstruction
• Arrhythmia
PAPILLARY FIBROELASTOMA
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Incidental finding - autopsy
Located on valves
Hair-like projections
Myxoid connective tissue, elastic fibers
& mucopolysaccharides
CARDIAC EFFECTS OF
TUMOURS
NON-CARDIAC
• Melanoma, Leukemia, Lymphoma,
Carcinoma breast, lung, oesophagus &
kidney
• Effects due to infiltration, mediators or
tumour therapy
• Pericardial effusion, tamponade
CARDIOVASCULAR EFFECTS OF
NON-CARDIAC NEOPLASMS
MYOCARDITIS
Inflammation of myocardium causing
myocardial injury
WHO- 14 polysmorphs/ square milimeter, 1
macrophage
MAJOR CAUSES OF MYOCARDITIS
INFECTIONS
Viruses (e.g. coxsackievirus, ECHO, influenza, HIV
cytomegalovirus)
Chlamydia (e.g. C, psittaci)
Rickettsiae (e.g. R, typhi, typhus fever)
Bacteria e.g. Corynebacterium diphtheriae, Neisseria
meningococcus, Borrelia (Lyme disease)
Fungi (e.g. Candida)
Protozoa (e.g. Trypanosoma, Chagas disease,
disease, toxoplasmosis)
Helminths (e.g. trichinosis)
MAJOR CAUSES OF MYOCARDITIS (CONTD)
Immune-Mediated Reactions
Postviral
Poststreptococcal (rheumatic fever)
Systemic lupus erythematosus
Drug hypersensitivity (e.g. methyldopa,
sulfonamides)
Transplant rejection
Unknown
Sarcoidosis
Giant cell mycoarditis
MYOCARDITIS
Gross: Flabby, Dilated, Mottled Mural
thrombi
Endomyocardial biopsy:
I/S inflammation composed of lymphocytes,
monocytes
MYOCARDITIS
Hypersensitivity Myocarditis
Perivascular Lymphocytes, monocytes and
eosinophils
MYOCARDITIS
Giant cell Myocarditis
Giant cells, lymphocytes, monocytes,
plasma cells, macrophages
Poor prognosis
MYOCARDITIS
Chagas diseaseTrypansoma cruzi
South America
Acute attach- 10% mortality
Cardiac insufficiency- 10- 20 yrs
MYOCARDITIS
Diphtheria- Toxin
Borellia burgdorferi- conducting system
HIVInflammation, myocyte damadge
Myocarditis
MYOCARDITIS
LABSerology
Biopsy- Viral DNA, RNA
CLINICAL FEATURES - MYOCARDITIS
• Broad clinical spectrum
• Asymptomatic to CHF or sudden
death
• Fever, dyspnoea, fatigue, palpitation,
chest pain
• May mimic MI
• May proceed to DCM
PERICARDITIS & EFFUSION
• Normal fluid 30-50 ml
• Blood, Pus, Straw coloured fluid
• Slow accumulation (<500 ml) - Globular
Heart
• Rapid collection - tamponade
CAUSES OF PERICARDITIS
MORPHOLOGICAL CLASSIFICATION
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Serous pericarditis
Serofibrinous / fibrinous pericarditis
Purulent pericarditis
Haemorrhagic pericarditis
Caseous pericarditis
Adehesive mediastinopericarditis
Constrictive pericarditis
HAEMORRHAGIC PERICARDITIS
• CAUSES
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T.B
Malignancy
Trauma
Cardiac surgery
Bleeding diathesis
Anti - coagulant
therapy
CASEOUS PERICARDITIS
• Tuberculosis
• Fungi
• Results in calcific, fibrocalcific
pericarditis
FIBRINOUS & SEROFIBRINOUS
PERICARDITIS
• MI, post infraction
syndrome, uraemia,
radiations, rheumatic
fever, SLE, trauma
• Friction rub
• Yellow cloudy exudate
• Dry rough, granular
surface
• Bread and Butter
appearance
PURULENT PERICARDITIS
• Source of infection
– Direct spread
– seeding from blood &
lymphatics
– introduction during surgery
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Thin to creamy pus (400500 ml)
• May lead to constrictive or
mediastino- pericarditis
CONSTRICTIVE PERICARDITIS
• Fibrous / Fibrocalcific
case
• Concretio cordis
• Limits diastolic function
• Low cardiac output
• Pericardiotomy
ADHESIVE
MEDIASTINOPERICARDITIS
• Suppurative, caseous, irradiation,
cardiac surgery
• Obliterated pericardial sac
• Strain on cardiac function
• Retraction of ribs, diaphragm & pulsus
paradoxus
• Leads to cardiac hypertrophy or
dilatation
COMPLICATIONS OF
PERICARDITIS
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Tamponade
Adhesive pericarditis
Impairment of cardiac function
Adhesion with surrounding structures
Constriction
CARCINOD HD
Figure 12-29 Carcinoid heart disease. A, Characteristic endocardial fibrotic lesion involving the right ventricle and tricuspid valve. B, Microscopic appearance of carcinoid heart disease
with intimal thickening. Movat stain shows underlying myocardial elastic tissue black and acid mucopolysaccharides blue-green.
Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 27 October 2005 04:48 AM)
© 2005 Elsevier
Figure 12-29 Carcinoid heart disease. A, Characteristic endocardial fibrotic lesion involving the right ventricle and tricuspid valve. B, Microscopic appearance of carcinoid heart disease
with intimal thickening. Movat stain shows underlying myocardial elastic tissue black and acid mucopolysaccharides blue-green.
Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 27 October 2005 04:48 AM)
© 2005 Elsevier
TRANSPLANTATION
Figure 12-39 Complications of heart transplantation. A, Cardiac allograft rejection typified by lymphocytic infiltrate, with associated damage to cardiac myocytes. B, Graft coronary
arteriosclerosis, demonstrating severe diffuse concentric intimal thickening producing critical stenosis. The internal elastic lamina (arrow) and media are intact (Movat pentachrome stain,
elastin black). (B, reproduced by permission from Salomon RN, et al: Human coronary transplantation-associated arteriosclerosis. Evidence for chronic immune reaction to activated graft
endothelial cells. Am J Pathol 138:791, 1991.)
Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 27 October 2005 05:18 AM)
© 2005 Elsevier
TRANSPLANTATION
3000/ year
First human-human: 1967
Improved outcomeImmunosuressive therapy- Cyclosporin A
Glucocorticoids
Selection of candidates
Early diagnosis of allograft rejection
COMPLICATIONS OF
TRANSPLANTATION
Rejection
A0- No rejection
R1- mild rejection
R2- moderate rejection- pri vascular
lympho
R3- severe rejection- myocyte injury,Neu
Eo, lym
D/D myocarditis- fatal
COMPLICATIONS OF
TRANSPLANTATION
Rejection
Stenosing intimal proliferation- I/Mural vessels
Silent infarction
Pathogenesis:
Chronic inflammation- GF- Smooth muscles
proliferation
Extracellular matrix- intimal expansion