Pathology: Cardiomyopathy

Front 1

Definition of Cardiomyopathy & Myocarditis:

What are some common things that are NOT included?

Back 1

*Heart disorders where the primary abnormality resides in the myocardium itself;

*Excluded are heart muscle impairments due to other known cardiovascular conditions, like:
-Hypertension
-Valvular heart disease
-Atherosclerotic coronary artery disease (so-called ischemic cardiomyopathy).

Front 2

∆ b/t 1˚ and 2˚ cardiomyopathy?

What end points do these lead to?

Back 2

*Primary: predominately confined to the heart.

*Secondary: myocardial involvement as part of generalized multiorgan disorders.

*Leads to sudden death or heart failure related disability.

Front 3

What Conditions are Associated with Heart Muscle Disease? 7

Back 3

*Infections (inflammatory cardiomyopathies /myocarditis):
-Viruses, bacteria, protozoa.

*Toxins / drugs:
-Alcohol, lithium, chemotherapy, phenothiazines, chloroquine, cocaine.

*Metabolic:
-Hypo/hyperthyroidism, K abnormalities, nutritional.

*Neuromuscular diseases
-Friedreich ataxia, muscular dystrophy.

*Storage disorders:
-Inborn errors of metabolism, amyloidosis.

*Infiltrative:
-Leukemia, metastatic cancer, sarcoidosis, radiation- induced fibrosis.

*Immunologic:
-Rheumatic heart disease, post-transplant rejection.

Front 4

What are the 3 basic types of cardiomyopathy?

What is classification based on? 2

Back 4

*Based on:
-Anatomic appearance.
-Functional abnormality.

1) Dilated cardiomyopathy (DCM).
2) Hypertrophic cardiomyopathy (HCM).
3) Restrictive cardiomyopathy (RCM).

Front 5

What are other, less common types of cardiomyopathy (unclassified)?

Back 5

-Arrythmogenic right ventricular dysplasia (cardiomyopathy) (ARVD).

-Isolated LV non-compaction.

-Stress cardiomyopathy.

-Non structural: heart is normal after gross and histological examination--> Ion channelopathies (myocardial electrical diseases).

Front 6

Definitions of Dilated, Hypertrophic, and Restrictive cardiomyopathy:

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*Dilated cardiomyopathy (90%):
-LV chamber enlargement / minimal hypertrophy.
-Impaired systolic contraction.

*Hypertrophic cardiomyopathy:
-LV thickening.
-Abnormal diastolic relaxation.

*Restrictive cardiomyopathy:
-Stiffened myocardium.
-Diastolic relaxation impaired / systolic function usually OK.

Front 7

Gross anatomy of heart: frontal section quick review:

Back 7

Front 8

Discuss Dilated cardiomyopathy:
what causes it?

Back 8

*3rd most common cause of heart failure. Caused by:

1) Genetic mutations.

2) Infection:
-Viruses (coxsackie virus, cytomegalovirus, ECHO virus, HIV virus, Epstein-Barr virus, influenza virus)

3) Toxins: Alcohol, cocaine.

4) Autoimmune and systemic disorders.

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Talk about Genetic and Acquired Cardiomyopathy:

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*ACQUIRED:
-Inflammatory (commonly myocarditis).
-Toxic: Alcohol, Chemotherapy (adriamycin), cocaine.
-Pregnancy-associated.

*GENETIC (25-35%):
-Neuromuscular: Muscular or myotonic dystrophy.

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Discuss DCM: Acquired: Pregnancy-associated cardiomyopathy:

Back 10

*Peripartum cardiomyopathy (PPCM).

*Occurs late in pregnancy or several weeks to months after delivery.

*Poorly understood causes:
-Pregnancy associated hypertension.
-Volume overload.
-Nutrition &/or metabolic abnormalities.
-Poor contractile reserve.

Front 11

Discuss DCM: Acquired Alcohol cardiomyopathy:

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*Alcohol &/or acetaldehyde may have toxic effect on myocardium, by inhibition of oxidative phosphorylation & fatty acid oxidation.

*Nutritional deficiencies often associated with ethanol intake may play a role (ex. thiamine deficiency).

*May be reversible if they stop ethanol intake.

*Note effect (on graph) of etoh and EF.

Front 12

Discuss DCM: Genetic Causes (Familial Cardiomyopathy):

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*Most are autosomal dominant, some X-linked or mitochondrial inheritance.

*Most are abnormalities that affect the myocyte cytoskeleton:
-Some affect mitochondrial genes (children) for proteins that enable oxidative phosphorylation & fatty acid oxidation.

*The X-linked form is best understood:
-Mutation in gene for DYSTROPHIN (cell membrane-based cytoskeletal protein).

Front 13

Discuss Dilated cardiomyopathy: Pathology: Gross appearance--

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*Heavy / 2-3x normal.
*Large, flabby, dilated.
*Walls usually thinned (may be normal or thickened) but out of proportion to dilation of the chamber.
*Valves are intrinsically normal.
*Coronary arteries are normal or any atherosclerosis is insufficient to explain the myocardial disease.

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Gross appearance of heart in dilated cardiomyopathy. "GLOBULAR HEART."

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*Gross appearance of heart in dilated cardiomyopathy. *Dilated LV cavity, thin wall.

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*Gross appearance of heart in dilated cardiomyopathy. *Dilated LV cavity, thin wall.
*Arrow points to a mural thrombus.

Front 17

Discuss Dilated cardiomyopathy: Histology:

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*Histology:
-Myocytes hypertrophied with enlarged nuclei.
-Some myocytes are atrophied and stretched.
-Interstitial fibrosis & myocyte dropout.

*Is nonspecific & usually nondiagnostic of a specific etiology.

*Not correlated with functional impairment.

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*Histologic appearance of myocardium in DCM.
*Blue=fibrous
*Some hypertrophied nuclei.
*This is non-diagnostic, but it's what you see.

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*Gross and Histologic appearance of myocardium in DCM.
*Fibrosis.

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*Gross and Histologic appearance of myocardium in DCM.
*Fibrosis, elongated myocytes.

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Pathophysiology of DCM:

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*Ventricular stroke volume declines & cardiac output declines.

*Compensation:
-Frank-Starling mechanism to increase stroke work--Greater stretch, greater force of contraction.

-Neuro-hormonal mechanisms to increase heart rate and contractility:
1) Adrenergic nervous system.
2) Renin-angiotensin system.

Front 22

DCM: Signs & Symptoms-- 5

Back 22

*Decompensation & complications:
-Congestive heart failure.
-Edema.
-Valvular regurgitation due to stretching of valve rings.
-Atrial dilatation & resultant fibrillation.

Front 23

Define Hypertrophic Cardiomyopathy:

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*Hypertrophic obstructive cardiomyopathy or "idiopathic subaortic stenosis."

*Definition:
1) Myocardial left ventricular hypertrophy.
2) Abnormal diastolic filling , with intermittent aortic outflow obstruction (LVOT-left ventricular outflow tract) in 1/3rd of cases.
3) LV hypertrophy not due to pressure overload (i.e. not hypertensive hypertrophied heart).

*HCM is one of the most common cardiac causes of sudden death in children, adolescents, & young adults.

Front 24

Discuss Sporadic and Genetic HCM:

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*Sporadic (i.e. idiopathic).

*Genetic– autosomal dominant (with variable penetrance).
-Mutation in genes that encode proteins for the contractile unit of the myocyte – the sarcomere.
-Most common sarcomere protein mutations are in:
1) Beta myosin heavy chain.
2) Myosin binding protein C.
3) Cardiac troponin T.

Front 25

Discuss Hypertrophic Cardiomyopathy: Pathology: Gross Appearance--

Back 25

*Gross appearance: massive hypertrophy without chamber dilatation.
-90% of cases show asymmetric hypertrophy of ventricular septum.
-Ratio of septum to LV free wall > 1.3.

*Shape of ventricular cavity is slit-like, compressed (“banana-like”).

*Possible endocardial thickening with mural plaque due to contact with the anterior mitral valve leaflet.

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*Gross appearance of heart in hypertrophic cardiomyopathy.
*Thick septum thicker than free wall.

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*Gross appearance of heart in hypertrophic cardiomyopathy.

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Gross appearance of heart in hypertrophic cardiomyopathy.

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*Gross appearance of heart in hypertrophic cardiomyopathy.

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Discuss Hypertrophic Cardiomyopathy: Histology--

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*Histology: IS DIAGNOSTIC!
-Marked myocyte hypertrophy ( > than in hypertensive heart disease).

-DISARRAY of myocytes – short, wide, chaotic in direction with increased lateral attachments.

-Interstitial fibrosis.

Front 31

Discuss myocyte disarray in HCM:

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*Architectural disorganization of the cardiomyocytes:
-Either isolated or in fascicles.
-Either perpendicular or oblique alignment to each other.
-In a pinwheel or herring bone pattern.

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*Fascicle disarray: Disarray of single myocytes in HCM.
*This is diagnostic.

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Histologic appearance of myocytes in HCM.

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*Hypertrophic cardiomyopathy: Ultrastructural level: spatial disorganization of myofibrils within the myocytes.
*Chaotic.

Front 35

Discuss Hypertrophic cardiomyopathy: Pathophysiology--

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*Predominant feature is reduced compliance and relaxation of the chamber– diastolic filling is impaired.

*Pressures are transmitted backward to produce elevated left atrial, pulmonary venous, and capillary pressures.

Front 36

Pathophysiology of HCM: discuss LVOT obstruction and the Venturi effect.

Back 36

*In the asymmetric form-- transient systolic obstruction in 1/3 of the cases.

*Hypertrophic cardiomyopathy with outflow obstruction
-The thickened upper interventricular septum causes transient LV outflow obstruction d/t abnormal motion of the ANTERIOR mitral valve LEAFLET toward the septum--> MID-LATE MURMUR.

-The systolic pressure gradient is “dynamic” (varies during contraction in proportion to the distance between the anterior mitral leaflet & the septum).

-The force of flow through the narrowed LV outflow channel forces the anterior mitral valve leaflet toward the thickened septum (Venturi effect).

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*LVOT obstruction in HCM.
*Arrow points to fibrous scar tissue due to anterior leaflet flapping.

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LVOT obstruction in HCM.

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Signs and Sx of HCM:

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1) Angina: due to increased muscle mass, high filling pressures & diastolic dysfunction (not atherosclerotic coronary artery disease).

2) Syncope: due to outflow obstruction & reduced stroke volume d/t impaired diastolic filling.

3) 1/3rd have harsh dynamic (changing) systolic ejection murmur.

4) Sudden death due to cardiac arrhythmias, especially during exercise.

5) Atrial fibrillation, mural thrombi, infective endocarditis of the mitral valve.

Front 40

HCM: Differential Diagnosis:

Back 40

*Left ventricular hypertrophy due to:
1) Hypertensive heart disease.
2) Aortic stenosis.

Front 41

Discuss HCM: Treatment--

Back 41

1) Surgical myomectomy. Surgical excision of muscle mass in septum.

2) Reduction of muscle mass by selective infarction using intravascular infusion of ethanol.

3) Pharmacologic: beta-blockers.

4) Pacemakers/defibrillators.

5) Cardiac transplant.

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*HCM: s/p myomectomy via RV approach; arrow shows indentation from myomectomy.

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HCM: myomectomy via LV approach; arrow shows indentation in LV where muscle was removed

B. surgical specimen shows endocardial fibrosis of LV outflow tract plaque.

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HCM. Post mortem.

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HCM. Extensive myofiber disarray. High power; H&E stain.

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HCM. Trichrome stain (collagen) myofiber disarray.

Front 47

Compare and contrast DCM and HCM:

Back 47

Front 48

Define Restrictive Cardiomyopathy.
What are the two mechanisms of RCM?

Back 48

*Definition: Impaired diastolic filling; a disease of ventricular compliance.
-Abnormally stiff, rigid, but not necessarily thickened ventricle.

*Two mechanisms:
1) Fibrosis &/or scarring of the endocardium.
2) Infiltration of myocardium by abnormal substances.

Front 49

Restrictive Cardiomyopathy: Types--

Back 49

1) Idiopathic.

2) Endomyocardial conditions:
-Endomyocardial fibrosis.
-Loefflers endomyocarditis.
-Endocardial fibroelastosis.

3) Diseases/conditions that can affect the myocardium:
-Radiation fibrosis.
-Amyloidosis.
-Sarcoidosis.
-Hemochromatosis.
-Metastatic tumor.
-Inborn errors of metabolism.

Front 50

Discuss Restrictive Cardiomyopathy Pathology-- Gross:

Back 50

-Ventricles of normal thickness & chamber size.
-Myocardium is firm & may be abnormal in color.
-Bi-atrial dilatation is common.
-Endocardium may be opaque & thickened.

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*RCM: biatrial dilatation; normal thickness of ventriclar wall and ventricular cavities of normal size.

Front 52

Discuss Restrictive Cardiomyopathy Histology:

Back 52

-Patchy interstitial fibrosis.
-Appearance of endocardium &/or myocardium may be diagnostic of specific disease process.

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RCM. Dilated left atrium.

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Back 54

Restrictive cardiomyopathy: Amyloidosis shows green birefringence.

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RCM histology: amyloidosis. Pink abnormal material deposited in b/t the heart muscle.

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Back 56

RCM; hemochromatosis, Fe stain.
*Blue = Fe

Front 57

What error of metabolism can cause RCM?

Back 57

*Lysosomal storage disease:
-Glycogen storage disease (II – Pompe’s) due to deficiencies of lysosomal enzyme glucosidase.

Front 58

Back 58

RCM: heart in glycogen storage disease Type II (Pompe’s disease). Note strange histological appearance due to glycogen.

Front 59

Discuss Endocardial Pathology in RCM:

Back 59

*Endomyocardial fibrosis:
-Disease of children & young adults in Africa & tropical areas.
-Endocardium from apex to valves is fibrotic.

*Loeffler endomyocarditis:
-Occurs in any geographic area.
-Marked endocardial fibrosis.
-Associated with abnormal eosinophils & release of their toxic products (major basic protein).
-May be associated with eosinophilic leukemia.

*Endocardial fibroelastosis:
-A disease of neonates & infants.
-Shiny, firm, thickened endocardium in ventricles.
-Composed of fibrosis & elastic tissue.
"Porcelain heart"

Front 60

Back 60

Endocardial fibroelastosis in RCM.
Thickened and white. "porcelain"

Front 61

Pathophysiology of RCM:

Back 61

*Increase ventricular filling pressures throughout diastole with decreased ventricular filling.

*Intraventricular pressures increase dramatically with a small increase in volume:
-Elevated systemic & pulmonary venous pressures.
-Decreased stroke volume & cardiac output.

Front 62

Discuss RCM: Signs & Symptoms--

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*More RIGHT-sided heart failure than left.

*Edema & venous congestion (hepatomegaly, ascites, JVD).

*Weakness, fatigue.

Front 63

Differential for RCM:

Back 63

*Constrictive PERICARDITIS.

Front 64

*Summary of Cardiomyopathies*

Back 64

*Dilated cardiomyopathy (90%):
-LV chamber enlargement / minimal hypertrophy.
-Impaired systolic contraction.
-Progressive LV enlargement leads to heart failure & emboli.

*Hypertrophic cardiomyopathy:
-LV thickening.
-Abnormal diastolic relaxation.
-Dynamic outflow obstruction during systole may be present.
-Results in dyspnea, angina, and death during exercise.

*Restrictive cardiomyopathy:
-Stiffened myocardium of fibrotic endocardium.
-Diastolic relaxation impaired / systolic function usually OK.
-Signs of right & left ventricular failure.

Front 65

Discuss Arrhythmogenic right ventricular cardiomyopathy:

Back 65

*Arrhythmogenic RV dysplasia (ARVD).

*Portions of the right ventricle are thin and lack myocytes; usually containing only fatty infiltration & fibrosis.

*Associated with right sided heart failure, arrhythmias, ventricular tachycardia & sudden death.

Front 66

Etiologies of Arrhythmogenic RV Dysplasia:

Back 66

*Myocyte degeneration which may be inherited.

*Interstitial inflammation:
-Infectious (probably post-viral).
-Autoimmune.

Front 67

Discuss the role of desmosomes in Arrhythmogenic RV Dysplasia:

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*40% of patients with ARVC have mutation(s) in genes encoding desmosomal proteins--> Cardiocutaneous syndromes (ARVC is associated with changes in hair and skin).

*Desmosomes are intercellular adhesion juctions in the intercalated disks.
-Cadherin family of adhesion molecules.

*Abnormal cell-cell adhesions injures cardiac myocytes.

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Arrhythmogenic RV cardiomyopathy. Note lack of muscle and lots of fat and fibrous tissue in RV wall.

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ARVC-gross & macro. Note lack of muscle and lots of fat and fibrous tissue in RV wall.

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Arrhythmogenic right ventricular cardiomyopathy. Note lack of muscle and lots of fat and fibrous tissue in RV wall.

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Arrhythmogenic right ventricular cardiomyopathy.

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Arrhythmogenic right ventricular cardiomyopathy. Residual myocytes trapped within fibrous & adipose tissue. Note lack of muscle and lots of fat and fibrous tissue.

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*Arrhythmogenic right ventricular cardiomyopathy.
Left panel: right ventricular chamber dilatation
Right panel: nearly transmural replacement by adipose tissue & thinned aneurysmal area (inferiorly).

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*Arrhythmogenic right ventricular cardiomyopathy.
*Adipose tissue with small island of subendocardial myocytes with fibrous tissue (trichrome stain).

Front 75

What is Isolated left ventricular non-compaction?

Back 75

*2-layer structure:
-Thick endocardial layer of trabecular meshwork.
-Deeper thin compacted myocardium.

*Prominent trabeculations.

*Deep recesses in apex of left ventricle.

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Isolated LV Non-compaction. At apex and free wall.

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Isolated LV Non-compaction. In RV, too.

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Isolated LV Non-compaction: Histology (* = areas of scarring).

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*LV Non-compaction (LVNC): “sponge myocardium.”

*Intrauterine arrest of compaction of endomyocardial morphogenesis leading to persistence of embryonic myocardium.

Front 80

Discuss Stress cardiomyopathy:

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*Takotsubo cardiomyopathy, left ventricular apical ballooning syndrome, "broken heart" syndrome.

*Catecholamine-mediated myocardial stunning.
-Emotional, physiological and physical stress associated with increased rates of sudden death.
-Some associated with genetic differences in components that encode catecholamine biosynthesis, storage & metabolism.

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*Fatal case of 50-year old woman with stress cardiomyopathy due to being attacked & robbed. 
*Arrows = typical end-systolic takotsubo feature.

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*Takotsubo cardiomyopathy (apical ballooning syndrome or "broken heart" syndrome).
*Diastolic (c) & systolic (D) ventriculogram.

Front 83

Pathophysiology of stress cardiomyopathy:

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*Contraction band necrosis in stress cardiomyopathy.

Front 85

Cardiomyopathy: discuss Myocardial electrical diseases--

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*Are non-structural heart diseases with defects invisible even at ultrastructural levels by electron microscopy.

*Manifest with arrhythmias & conduction disturbances & sudden death.

*The myocyte is abnormal at the molecular level, due to ion channel gene mutations.

Front 86

Run through the types of ion channelopathies: 3

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*Long & short QT syndromes:
-Na or K ion channel diseases of the cell membrane.

*Brugada syndrome:
-Na ion channel disease.

*Polymorphic ventricular tachycardia:
-Abnormal ryanodyne receptor regulating Ca release from sarcoplasmic reticulum.

Front 87

Cardiomyopathy: Is it time for a genomic rather than a morphologic classification?

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Front 88

What characterizes myocarditis?

Back 88

*Presence of inflammatory infiltrate.

*Associated myocyte necrosis or damage that's not characteristic of an ischemic event (i.e. Not coagulative necrosis from a myocardial infarction).

Front 89

Define myocarditis:
3 types?

Back 89

*Inflammatory cardiomyopathies.

*Definition
-Primary inflammatory processes that injure myocytes.
-Not inflammation that is a secondary to ischemic necrosis (myocardial infarction) due to ASCAD, or to traumatic injury.

*Three Types:
1) Infection that directly injures myocytes.
2) Autoimmune noninfectious myocyte injury-- immune responses that cross-react with myocardial cell proteins, like allergic reactions, systemic immune diseases, transplant rejection.
3) Idiopathic.

Front 90

Discuss the Major causes of Myocarditis:
3 big categories:

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*Infections:
1) Viruses (e.g., coxsackievirus, ECHO, influenza, HIV, cytomegalovirus).
2) Chlamydiae (e.g., C. psittaci).
3) Rickettsiae (e.g., R. typhi, typhus fever).
4) Bacteria (e.g., Corynebacterium diphtheriae, Neisseria meningococcus, Borrelia (Lyme disease).
5) Fungi (e.g., Candida).
6) Protozoa (e.g., Trypanosoma cruzi [Chagas disease], toxoplasmosis).
7) Helminths (e.g. trichinosis).

*Immune-mediated reactions:
1) Postviral.
2) Poststreptococcal (rheumatic fever).
3) Systemic lupus erythematosus.
4) Drug hypersensitivity (e.g., methyldopa, sulfonamides). 5) Transplant rejection.

*Unknown: Sarcoidosis, Giant cell myocarditis.

Front 91

Prevalence of the types and geography of Myocarditis: Infectious cardiomyopathies--

Back 91

-Viruses are most common in the US:
-Coxsackie viruses B (enteroviruses) echovirus.
-Human immunodeficiency virus (HIV).

*Bacteria:
-Often associated with endocarditis or sepsis.
-May be associated with Lyme disease (Borrelia burgdorferi).

*Fungus in immunosuppressed (Candida).

*Protozoa: Trypanosoma cruzi (Chagas disease); most common in South America.

*Helminths: Trichinosis from undercooked pork.

Front 92

Describe the pathological gross appearance of myocarditis:

Back 92

-May be normal.

-Chambers may be dilated (“burned out” myocarditis may be a cause of dilated cardiomyopathy).

-May have pale foci or minute hemorrhagic lesions.

Front 93

Describe the composition of inflammatory infiltrate cells in myocarditis:

Back 93

*Composition of inflammatory infiltrate cells gives etiologic clues.

*Polymorphonuclear leukocytes: bacterial infection.

*Eosinophils: hypersensitivity reactions.

*Giant cells: mycobacterial and fungal infections.

*Lymphocytes: viral infections, systemic diseases.

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Myocarditis: gross abscesses seen through epicardium.

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Myocarditis: histology of microabscess. This person had sepsis that deposited in the heart.

Front 96

Discuss causes of Viral myocarditis by time of year:

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*Picornaviruses & Coxsackie B:
-cases in Spring (March to May).
-cases in summer (August).

*Influenza viruses in Winter months.

*Cardiotropic viruses: enteroviruses, adenoviruses, parvoviruses.

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*Florid lymphocytic myocarditis.
*Arrow: necrotic myocyte w/lymphocytes.
*This is diagnostic. And can kill you.

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Histology of Lymphocytic myocarditis.

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Myocarditis: Lymphocytic/Histiocytic infiltrate & T-lymphocytes.

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What are the three pathologically distinct phases for unresolved viral myocarditis?

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1) Initial direct insult to the myocardium.

2) Subsequent autoimmunity triggered, extensive myocardial injury.

3) Development of dilated cardiomyopathy.

Front 101

Myocarditis: What are the Noninfectious cardiomyopathies?

Back 101

*Allergic, hypersensitivity or immune myocarditis:
-Antibiotics (ampicillin), diuretics (HCT), antihypertensives.
-Poststreptococcal (Rheumatic fever), systemic lupus erythematosis, polymyositis.
-Transplant rejection.

*Giant cell myocarditis:
-Myocardial necrosis of uncertain cause.
-Characterized by a mixed inflammatory cell infiltrate containing multinucleate giant cells.

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*Eosinophilic myocarditis (left) due to hypersensitivity rxn.
*giant cell myocarditis (right).

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eosinophils in myocarditis due to hypersensitivity rxn.

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Giant cell myocarditis

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Giant cell myocarditis.

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Myocarditis in TB. Arrow points to caseous necrosis in the heart.

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Discuss diagnosis of Myocarditis:

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*Endomyocardial biopsy.
*Serologic demonstration of rising antibody titres in patient serum.
*Viral cultures & DNA technology.
*Immunoperoxidase staining.
*Cardiac imaging.
*Electrocardiograms.
*Cardiac biomarkers.

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What is the problem with using Endomyocardial biopsy to diagnose myocarditis?

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Chance of false negative result is high, because you're just sampling a small amount.

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Examples of biopsy specimens.

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Examples of biopsy specimens.

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*Extensive scarring of LV myocardium involving anterior & posterior walls (A).
*Microscopic features of old fibrosis (B).

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(A) A pan-carditis involving epicardium, myocardium & endocardium.
(B) Close up of inflammation in epicardium.

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*Different stages of myocardial lesions:
(A)-focal cellular infiltrates w/ myocardial cell necrosis.
(B)-infiltrating cells were mainly eosinophils w/some lymphocytes.

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(A) Luna stain of eosinophil granules.
(B) Myeloperoxidase stain of myeloperoxidase-positive granules in cytoplasm of eosinophils & around degenerating myocytes.

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Genetics of cardiomyopathy:

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