Cardiomyopathy

Question 1

What is cardiomyopathy?

Answer 1

Primary disease of the myocardium excluding damage by extrinsic factors

Question 2

What are the subtypes of cardiomyopathy?

Answer 2

• Dilated cardiomyopathy (DCM)
• Hypertrophic cardiomyopathy (HCM)
• Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)
• Restrictive Cardiomyopathy (RCM)

Question 3

What is the most common type of cardiomyopathy? What are the subtypes?

Answer 3

Dilated cardiomyopathy

1. Secondary
2. Primary

Question 4

What type of genetic transmission is most common in DCM?

Answer 4

Autosomal dominant

Question 5

1. What are mutated genes that encode for cytoskeletal proteins that result in DCM?
2. What are the mutated genes that encode for anchoring the cytoskeleton and the sarcolemma to the ECM?
3. What is the hypothesis of the genetic mutations that cause DCM?

Answer 5

1. Lammin A/C, Desmin, Metavinculin
2. Delta-sarcoglycan, dystrophin
3. Defects in force transmission lead to development of a dilated poorly contracting heart

Question 6

Besides genetic factors, what other factors can lead to DCM?

Answer 6

Viral myocarditis and immunologic abnormalities

Question 7

What is your Dx? What are the macroscopic findings? Microscopic findings?

Answer 7

Idiopathic Dilated Cardiomyopathy; Heart weight tripled, flabby/pale myocardium, conspicuous left/right ventricular dilation; Cardiacmyocytes show degeneration (Myocytolysis), perivascular fibrosis

Question 8

Pathogenesis of DCM?

Answer 8

1. Compensatory ventricular hypertrophy
2. Asymptomatic left ventricular dilation
3. Decrease exercise tolerance
4. Congestive HF

Question 9

What is the single most identifiable cause of DCM in the US?

Answer 9

Ethanol

Question 10

How can catecholamines cause DCM?

Answer 10

High concentrations of catechols cause focal myocyte necrosis (contraction band necrosis). Major mechanism is enhanced calcium influx into myocytes

Question 11

What types of medications are notorious for causing cardiomyopathy?

Answer 11

• Anthracyclines (ie doxorubicin) - mjr clinical effect - cardiac myocyte degeneration and decreased contractility
• Cyclophosphamide

Question 12

Describe the cardiac complications of pregnancy. Describe the molecular pathogenesis

Answer 12

In the last trimester or first 6 months following delivery, cardiomyopathy can occur.

1. Increased levels of biologically active prolactin
2. Results in increased blood volume, decreased blood pressure and diminshed renal excretion of water, sodium, and potassium

Question 13

What are the two genes associated with 80% of patients with HCM?

Answer 13

Beta-myosin and myosin binding protein C

Question 14

What is the proposed mechanism leading to HCM?

Answer 14

Mutant proteins are incorporated into sarcomeres where it acts as a dominant-negative fashion to cause loss of sarcomeric function. Therefore, there is altered force generation leading to compensatory hypertrophy

Question 15

What is you Dx? What macroscopic characteristics point toward this Dx?

Answer 15

Hypertrophic Cardiomyopathy; Asymmetric hypertrophy of the left ventricular wall (especially the septum), Septum bulges into left ventricle obstructing ventricular systole

Question 16

What are these histologic findings characteristic of? What’s going on here? Where are these changes most commonly seen?

Answer 16

Hypertrophic cardiomyopathy; Myofiber disarray - oblique and perpendicular myocytes; Interventricular septum

Question 17

What Syx are observed in HCM? What are patients with HCM at risk of? What are the complications of HCM in the heart?

Answer 17

Rarely any!; Sudden cardiac death; Ejection fraction and SV are high, muscle compliance is low (diastolic dysfn.)

Question 18

What are the Tx for HCM?

Answer 18

1. Beta Blockers
2. Calcium Blockers
3. Surgical removal of portion of the heart to unblock systolic obstruction

Question 19

The heart of a young Mediterranean who experienced a sudden death is shown below. What is your Dx? What is the molecular pathogenesis of this condition?

Answer 19

Arrhythmogenic Right Ventricular Cardiomyopathy; Mutations in genes encoding proteins in desmosomes are the main culprit in the pathogenesis

Question 20

What is restrictive cardiomyopathy? Describe how it causes pathology

Answer 20

Group of diseases in which myocardial or endocardial abnormalities limit diastolic filling while contractile function remains normal.

Question 21

What are the four major causes of restrictive cardiomyopathy?

Answer 21

1. Amyloid/Metastatic Carcinoma/Sarcoid Granules
2. Endomyocardial disease characterized by fibrotic thickening
3. Genetic storage disease (ie hemochromatosis)
4. Marked increase in interstitial fibrous tissue

Question 22

What are the anatomical changes found in restrictive cardiomyopathy?

Answer 22

1. Increased preload
2. Defective diastolic compliance
3. Restricted ventricular filling
4. Atrial Dilation
5. Venous Congestion

Question 23

What is the relationship between amyloidosis and the dimensions of the heart?

Answer 23

Amyloid infiltration results in cardiac enlargement without ventricular dilation

Question 24

What are the main Syx in cardiac amyloidosis?

Answer 24

Right sided heart failure

Question 25

What protein is deposited in senile cardiac amyloidosis? What are the Syx?

Answer 25

Transthyretin (prealbumin); Usually no Syx

Question 26

What are the two subtypes of endomyocardial disease?

Answer 26

1. Endomyocardial fibrosis - Africa 2. Eosinophilic Endomyocardial Disease (Loeffler endocarditis) - Temperate regions - hypereosinophilia

Question 27

What is the believed mechanism of myocardial injury?

Answer 27

Myocardial injury caused by eosinophils and possibly cardiotoxic granule components

Question 28

What is the pathogenesis of EMD?

Answer 28

1. Necrotic Stage - First Few Months - Eosinophilic infiltrate with vascular injury and myocyte necrosis 2. Thrombotic Stage - One year - Attached mural thrombi 3. Fibrotic stage - Chronic - Conspicuous fibrotic thickening of the endocardium

Question 29

Describe the effects of EMD on the valves of the heart

Answer 29

Adherence of the posterior mitral valve leaflet to endocardium - mitral regurg Adherence of tricuspid valve leaflet - tricuspid regurg

Question 30

What are 4 storage diseases that have restrictive cardiomyopathic changes?

Answer 30

1. Glycogen storage disease 2. Mucopolysaccharidoses 3. Sphingolipidoses 4. Hematochromatosis

Question 31

What glycogen storage diseases affect the heart? Which is the most severe?

Answer 31

1. II (Pompe Disease) 2. III (Cori Disease) 3. IV (Andersen Disease) Pompe is the worst

Question 32

What two Sphingolipidoses commonly cause cardiac complications?

Answer 32

* Fabry Disease - Glycosphingolipid accum. w/i heart * Gaucher Disease - rarely involves the heart

Question 33

A patient expires and on autopsy, the heart is dilated and the ventricular walls are thickened. The myocardium is notably browned. The patient appears to have died of congestive heart disease. What is the Dx? What is the best predictor of disease progression?

Answer 33

Hemochromatosis; Severity of myocardial dysfn. is proportional to quantity of deposited iron.

Question 34

A patient has a heart block and dies of arrhythmia. A biopsy of the interventricular septum shows noncaseating granulomas with prominent giant cells. What is the Dx? What part of the heart does this disease have a tropism for?

Answer 34

Cardiac sarcoidosis