Pathology of Primary Myocardial Disease

Question 1

What are the three main types of cardiomyopathy, and the most common one?

Answer 1

1. Dilated cardiomyopathy - most common
2. Hypertrophic cardiomyopathy
3. Restrictive cardiomyopathy

All three are primary myocardial disorders

Question 2

What is the cause of most dilated cardiomyopathy? What is the second most common cause?

Answer 2

1. Idiopathic - cause unknown
2. Genetic abnormalities (1/3 of cases) - usually autosomal dominant, affecting structural proteins of the myocardial cytoskeleton

Question 3

What are some other important causes of dilated cardiomyopathy not in the top two?

Answer 3

Toxicities:
1. Alcoholism + thiamine deficiency (wet beriberi), leading to myocardial death
2. Drugs - i.e. doxorubicin
S/p myocarditis: usually enteroviruses like Coxsackievirus
3. Pregnancy related - due to hemodynamic alterations / nutritional factors
4. Hypothyroidism - increases Na+, giving volume overload

Question 4

How does the heart appear in dilated cardiomyopathy grossly and microscopically?

Answer 4

Grossly - Large, heavy, globoid with four-chamber dilatation and variable hypertrophy / mural thrombi

Microscopically - Myocardial hypertrophy with interstitial fibrosis

Question 5

What is the pathogenesis of dilated cardiomyopathy? What other dysfunctions will be present?

Answer 5

Something causes myocardial dysfunction, leading to progressive SYSTOLIC dysfunction

• > presentation is worsening congestive heart failure
• > can be complicated with arrhythmias, valvular dysfunctions (large annuli), and embolic events

Question 6

What is arrhythmogenic right ventricular cardiomopathy?

Answer 6

A distinctive form of dilated cardiomyopatthy characterized by RV replacement with fat & fibrous tissue

-> right-sided heart failure and arrhythmias

Question 7

What is the usual cause of hypertrophic cardiomyopathy?

Answer 7

USUALLY autosomal dominant mutations in sarcomere proteins leading to decreased cardiac myocyte contractility
-> growth-factor induced hypertrophy and fibrosis

Question 8

What is the ventricular shape in hypertrophic cardiomyopathy and why? What can this damage?

Answer 8

Banana-shaped LV cavity
-> subaortic region will typically have an increased thickness blocking the outflow track of the LV, causing subaortic stenosis and damage to mitral valve and its underlying region

Question 9

What happens as a result of hypertrophic cardiomyopathy in each stroke?

Answer 9

Impaired diastolic filling -> decreased cardiac output

Systolic ejection murmur may be heard if septum leads to subaortic stenosis

Question 10

Is hypertrophy in hypertrophic cardiomyopathy symmetric or asymmetric? How will it appear microscopically?

Answer 10

Asymmetric -> LV hypertrophy is much greater, including IV septum

Microscopically -> hypertrophy with myofiber disarray and fibrosis

Question 11

How will patients with HCM present clinically?

Answer 11

Broad range of findings.

Arrhythmias -> diastolic dysfunction leads to LA dilatation and Afib

Systemic emboli from Afib

Progressive heart failure, angina, shortness of breath

May cause sudden cardiac death in young athletes from ventricular arrhythmias

Question 12

What does restrictive cardiomyopathy do to the heart?

Answer 12

Impairs diastolic filling, with minimal hypertrophy of the ventricles
-> leads to LA / RA dilatation from lack of compliance of ventricles

Question 13

What are the important causes of restrict cardiomyopathy?

Answer 13

1. Amyloidosis
2. Sarcoidosis (granulomatous)
3. Radiation-induced fibrosis
4. Hemochromatosis
5. Metastatic malignancy

Question 14

What is Takotsubo Cardiomyopathy also called?

Answer 14

“Octopus pot” or broken heart syndrome.

Question 15

What happens pathophysiologically to cause Takotsubo Cardiomyopathy?

Answer 15

Significant acute emotional or physical distress leads to excessive catecholamine release -> stuns myocardium of LV apex due to high concentration of sympathetic innervation, and causes multivessel coronary spasm

Stunning -> LV apical hypokinesis, looks alot like STEMI

Question 16

Who is typically affected with Takotsubo Cardiomyopathy and what will be their clinical manifestations / prognosis? What will angiography show? ECG?

Answer 16

Postmenopausal women -> chest pain / dyspnea, ECG abnormalities leads to ST segment elevation / T wave inversion, and elevated cardiac markers.

-> angiography shows no significant coronary obstruction and LV ballooning (looks like octopus pot)

Complete recovery in 1-2 months

Question 17

What is the most common cause of myocarditis?

Answer 17

Infections, and more specifically viruses
Enteroviruses (Coxsackie A and B, echoviruses)
CMV and HIV in immunocompromised

Question 18

What bacteria and parasites are known to cause myocarditis?

Answer 18

Bacteria - Borrelia burgdorferi - Lyme disease

Parasites - Trypanosoma cruzi, Toxoplasma in immunocompromised, Trichinella spiralis (helminth)

Question 19

What immunologic disorders are known to cause myocarditis?

Answer 19

Acute rheumatic fever - Aschoff bodies in myocardium

SLE - although pericarditis and valvular disease is much more common

Question 20

What are the usual microscopic features of myocarditis? Grossly?

Answer 20

Usually caused by viruses, so there will be interstitial inflammation, mononuclear cells / lymphs with focal myocyte injury (CD8 cells kill infected myocardium), leading to complete resolution or patchy fibrosis

Grossly - Slight color change with possible dilation of cardiac chambers

Question 21

How will myocarditis look if it is due to a drug-induced hypersensitivity?

Answer 21

Inflammatory cell infiltrate will also have many eosinophils

Question 22

What is giant cell myocarditis?

Answer 22

An idiopathic, aggressive form of myocarditis characterized by widespread myocardial cell loss, mononuclear infiltrate, and multinucleated giant cells

Question 23

Where does Chagas disease replicate?

Answer 23

Replicates as collections of amastigotes intracellular in smooth muscle and cardiac myocytes, causing a mixed inflammatory cell infiltrate in the myocardium + damage

Question 24

What are the clinical results of myocarditis?

Answer 24

Can be simply low-grade constitutional symptoms which are self resolving, to arrhythmias, to development of dilated cardiomyopathy

Question 25

What will be seen in cardiotoxicity caused by doxorubicin and cyclophosphamide?

Answer 25

Doxorubicin - Myocardial cell vacuolization & lysis, progressing to dilated cardiomyopathy

Cyclophosphamide - Myocardial hemorrhage (targets vessels more)

Question 26

What can be seen in cardiotoxicity caused by pheochromocytoma or cocaine?

Answer 26

Foci of myocardial contraction-band necrosis

Question 27

What types of cardiomyopathy does iron overload cause and why?

Answer 27

Early - restrictive cardiomyopathy from accumulation in cardiomycotes

Late - dilated cardiomyopathy from loss of cardiomyocytes from free radical damage

Question 28

What are the systemic amyloidoses which will affect both the ventricles and atria?

Answer 28

1. Senile cardiac amyloidosis - from transthyretin
2. Primary amyloidosis - AL light chain
3. Secondary amyloidosis - serum amyloid-associated protein (SAA) is a +APP

Question 29

What amyloidosis leads to amyloid accumulating only in the atrium?

Answer 29

Isolated atrial amyloidosis - derived from atrial natriuretic peptide, often in heart failure from volume overload

Question 30

What is the usual clinical outcome of cardiac amyloidosis?

Answer 30

Restrictive cardiomyopathy depending on where they deposit, leading to dilation of atria if primarily involving the ventricles for instance.

But again, restrictiveness will vary with location of protein deposition

Question 31

What will happen microscopically in cardiac amyloidosis?

Answer 31

Extracellular accumulation of amorphous eosinophilic material -> hyaline accumulation of amyloid proteins which stain with Congo red

Accumulation -> pressure atrophy of neighboring cardiac myocytes. Leads to a thickened, weak wall.