Chapter 11: Cardiomyopathies and Myocarditis

Question 1

What is cardiac disease due to?

Answer 1

intrinsic myocardial dysfunction

Question 2

What is the ‘name’ for intrinsic myocardial dysfunction

Answer 2

cardiomyopathies (literally: heart muscle diseases)

Question 3

True/false: cardiomyopathies can be primary or secondeary

Answer 3

True!

Question 4

Many disorders can be the cause of cardiomyopathies. Some are: inflammatory (i), immunologic (ii), systemic metabolic (iii), muscular dystrophies, and genetic disorders of myocardial fibres. Name examples of i, ii and iii (illustration)

Answer 4

i: myocarditis ii: sarcoidosis iii: hemochromatosis

Question 5

Is the cause of cardiomyopathies often known?

Answer 5

No (we call this ‘idiopathic’)

Question 6

There are many ways to classify cardiomyopathies, but for purposes of general diagnosis and therapy, however, three time-honored clinical, functional and pathologic patterns are recognized. Name those three.

Answer 6

1. Dilated cardiomyopathy (DCM) (including arrhythmo- genic right ventricular cardiomyopathy) 2. Hypertrophic cardiomyopathy (HCM) 3. Restrictive cardiomyopathy (from most to least frequent/common)

Question 7

Read this through

Answer 7

Okay

Question 8

Explain dilated cardiomyopathy (DCM)

Answer 8

Dilated cardiomyopathy (DCM) is characterized by progressive cardiac dilation and contractile (systolic) dysfunction, usually with concurrent hypertrophy; regardless of the cause, the clinicopathologic patterns are similar.

Question 9

Is DCM mostly acquired genetically or secondary?

Answer 9

Genetically (20-50%)

Question 10

DCM can however be a result from various acquired myocardial insults. Name some

Answer 10

• Myocarditis - Toxicities - Pregnancy (peripartum cardiomyopathy) - stress provoked - tachycardia induced

Question 11

In this picture you see the major forms of cardiomyopathy. Link the numbers (i-vi) with the correct diagnosis: a) dilated cardiomyopathy b) hypertrophic cardiomyopathy c) normal d) restrictive cardiomyopathy

Answer 11

i = c (normal)
ii = a (dilated cardiomyopathy)
iii = b (hypertrophic cardiomyopathy)
vi = d (restrictive cardiomyopathy)

Question 12

What are general causes that can lead to end-stage DCM besides genetics?

Answer 12

Infection - alcohol or other toxic exposure - peripartum cardiomyopathy - iron overload

Question 13

What is the fundamental defect in DCM?

Answer 13

Ineffective contraction (in end-stage, the cardiac ejection is typically less than 25% (normally l50-65%))

Question 14

What, besides ineffective contraction, are clinical features of DCM?

Answer 14

Secondary mitral regurgitation and abnormal cardiac rhythms are common, and embolism from intracardiac (mural) thrombi can occur

Question 15

What is arrhythmogenic right ventricular cardiomopathy?

Answer 15

Arrhythmogenic right ventricular cardiomyopathy is an autosomal dominant disorder that classically manifests with right-sided heart failure and rhythm disturbances, which can cause sudden cardiac death

Question 16

What is hypertrophic cardiomyopathy (HCM) characterized by?

Answer 16

Hypertrophic cardiomyopathy (HCM) is characterized by myocardial hypertrophy, defective diastolic filling, and— in one third of cases—ventricular outflow obstruc- tion.

Question 17

Fill in: In arrhythmogenic right ventricular cardiomyopathy, the wall is *thickened/thinned*. In hypertrophic cardiomyopathy, the wall is *thickened/thinned*

Answer 17

Thinned, thickened respectively

Question 18

What other disorders should be clinically distinguished from hypertrophic cardiomyopahy (because they are similar, but different treatment)?

Answer 18

HCM needs to be distinguished clinically from disorders causing ventricular stiffness (e.g., amyloid deposition) and ventricular hypertrophy (e.g., aortic stenosis and hypertension).

Question 19

True/false: Most cases of HCM are caused by missense mutations in one of several genes encoding proteins that form the contractile apparatus

Answer 19

True

Question 20

At what age is HCM, DCM, RCM and ARVC often diagnosed?

Answer 20

• HCM: postpubertal growth spurt
• DCM: 20-50y/o
• RCM: 4-6y/o (but can be at any age)
• Arrhythmogenic: 20-40y/o

Question 21

Explain (elaborately) the clinical features (NOT complications) of HCM (i don’t think we have to learn this)

Answer 21

t is characterized by massive left ventricular hypertorphy associated with (paradoxically) a markedly reduced stroke volume. This latter occurs as a consequence of impaired diastolic filling and overall smaller chamber size. In addition, roughly 25% of patients have dynamic obstruction to the left ventricular outflow by the anterior leaflet of the mitral valve. Reduced cardiac output and a secondary increase in pulmonary venous pressure cause exertional dyspnea, with a harsh systolic ejection murmur. A combination of massive hypertrophy, high left ventricular pressures, and compromised intramu- ral arteries frequently leads to myocardial ischemia (with angina), even in the absence of concomitant CAD.

Question 22

What are the major clinical complications of HCM?

Answer 22

Atrial fibrillation with mural thrombus formation, ventricular fibrillation leading to sudden cardiac death, infectious endocarditis of the mitral valve and CHF.

Question 23

How is restrictive cardiomyopathy characterized?

Answer 23

By a primary decrease in ventricular compliance, resulting in impaired ventricular filling during diastole (simply put, the wall is stiffer)

Question 24

True/false: restrictive cardiomyopahy is idiopathic

Answer 24

Yes, but it may also be associated with systemic diseases that affect the myocardium (e.g. radiation fibrosis, amyloidosis, sarcoidosis, errors metabolism)

Question 25

What are the three types of restrictive cardiomyopathy?

Answer 25

• Amyloidosis • Endomyocardial fibrosis • Loeffler endomyocarditis

Question 26

What is amyloidosis (of restrictive cardiomyopathy)? I don’t think you have to learn this, so just skim

Answer 26

Amyloidosis is caused by the deposition of extracellular proteins with a predilection for forming insoluble β-pleated sheets (Chapter 5). Cardiac amyloidosis can occur in the setting of systemic amyloidosis (e.g., mul- tiple myeloma) or can be predominantly restricted to the heart (e.g., senile cardiac amyloidosis). In the latter case, deposition of normal (or mutant) forms of transthyretin (a liver-synthesized circulating protein that transports thyroxine and retinol) in the hearts of older adult patients results in a restrictive cardiomyopathy. Four percent of African Americans carry a specific mutation of transthyretin that increases the risk of cardiac amy- loidosis in that population over fourfold. Besides depos- iting as amyloid, immunoglobulin light-chains in AL-type amyloid also are directly cardiotoxic and can induce myocardial dysfunction.

Question 27

What is endomyocardial fibrosis (of restrictive cardiomyopathy)? I don’t think you have to learn this, so just skim

Answer 27

Endomyocardial fibrosis is principally a disease of children and young adults in Africa and other tropical areas. It is characterized by dense diffuse fibrosis of the ventricular endocardium and subendocardium, often involving the tricuspid and mitral valves. The fibrous tissue markedly diminishes the volume and compliance of affected chambers, resulting in a restrictive physiology. Endo- myocardial fibrosis has been linked to nutritional defi- ciencies and/or inflammation related to helminthic infections (e.g., hypereosinophilia); worldwide, it is the most common form of restrictive cardiomyopathy.

Question 28

What is Loeffler endomyocarditis (of restrictive cardiomyopathy)? I don’t think you have to learn this, so just skim

Answer 28

Loeffler endomyocarditis also exhibits endocardial fibrosis, typically associated with formation of large mural thrombi. It has no geographic or population predilec- tion. It is characterized by peripheral hypereosinophilia and eosinophilic tissue infiltrates; release of eosinophil granule contents, especially major basic protein, prob- ably engenders endocardial and myocardial necrosis, followed by scarring, layering of the endocardium by thrombus, and finally thrombus organization. Of interest, some patients have an underlying hypereosino- philic myeloproliferative neoplasm driven by gene rear- rangements that lead to expression of constitutively active tyrosine kinases (Chapter 12). Treatment of such patients with tyrosine kinase inhibitors can result in hematologic remission and reversal of the endomyocar- dial lesions.

Question 29

True/false: in restrictive cardiomyopathy, the ventricles are slightly reduced

Answer 29

False! they are the normal size or slighly enlarged

Question 30

Explain the size, cavities (dilated/not) and myocardium (loose/firm) of restrictive cardiomyopathy

Answer 30

Size: same or slightly enlarged Cavities: not dilated Myocardium: firm

Question 31

What is myocarditis?

Answer 31

Myocarditis encompasses a diverse group of clinical entities in which infectious agents and/or inflammatory processes target the myocardium. It is important to distinguish myocarditis from conditions such as IHD, where the inflammatory process is secondary to some other cause of myocardial injury.

Question 32

What is the most common cause of myocarditis? Virus or bacteria?

Answer 32

Virus (most common US: coxsackieviruses A and B other enteroviruses)

Question 33

Can myocarditis be of a noninfectious cause?

Answer 33

Yes!

Question 34

What is a noninfectious cause of myocarditis?

Answer 34

Systemic diseases of immune origin, such as systemic lupus erythmatosus and polymyositis, but also drug hypersensitivity reactions of the heart

Question 35

What can be seen microscopically in acute myocarditis?

Answer 35

Edema, interstitial inflammatory infiltrates and myocyte injury (a diffuse lymphocytic infiltrate is most common, although the inflammatory involvement is often patchy and can be missed)

Question 36

What is seen microscopically in hypersensitivity myocarditis? (the type of cells)

Answer 36

Intersitial and perivascualr infiltrates are composed of lymphocytes, macrophages and a high proportion of eosinophils

Question 37

How is giant cell myocarditis mophologically distinctive?

Answer 37

By widespread inflammatory cell infiltrates containing mulinucleate giant cells (formed by macrophage fusion). It has poor prognosis

Question 38

How is chagas myocarditis characterized?

Answer 38

By the parasitization of scattered myofibers by trypanosomes accompanied by an inflammatory infiltrate of neutrophils, lymphocytes, macrophages, and occasional eosinophils

Question 39

Can myocarditis be asymptomatic?

Answer 39

Yes

Question 40

Can myocarditis cause death?

Answer 40

Yes

Question 41

What are other causes of myocardial disease (besides from infectious or systemic disease)?

Answer 41

Cardiotoxic drugs (tyrosine kinase inhibitors, immunotherapy, anthracyclins doxorubicin and daunorubicin, lithium, phenothiazines, catecholamines (cocaine) and chloroquine) (you obv don’t need to learn the toxins but i just wanted to show you)