Cardiomyopathies

Question 1

Three major forms cardiomyopathies

Answer 1

Dilated cardiomyopathy (DCM)
- includes ARDV 

Hypertrophic cardiomyopathy (HCM)

Restrictive cardiomyopathy

Question 2

Dilated cardiomyopathies details

Answer 2

Most common cardiomyopathy (90%)

Characterized by progressive cardiac dilation and contractile dysfunctions

Usually associated w/ eccentric Hypertrophy and low ejection fractions (systolic HF)

Question 3

5 pathways that leads to development of DCM

Answer 3

Genetic causes

Infection

alcohol/other toxic exposures

Peripartum cardiomyopathy

Iron overload

Question 4

Genetic causes for DCM

Answer 4

Is the basis for 20-50% of the DCM cases

Autosomal dominant inheritance patterns w/ over 50 genes being affected
- most common are mutations in genes that affect proteins that link sarcomere to the cytoskeleton

Can be X-linked as well, but in this case almost always revolves around dystrophin protein mutations

Question 5

Infection in DCM

Answer 5

Most common causative agents are they coxsacklevirus B and enteroviruses

Many cases may not show inflammation in the case of infections

Question 6

Alcohol/ toxin exposure in DCM

Answer 6

Alcohol abuse is strongly associated with DCM development
- causes thiamine deficiency which leads to wet beriberi heart disease

Other toxic agents include:

• cobalt
• doxorubicin
• chemo drugs

Question 7

Peripartum cardiomyopathy

Answer 7

Occurs late in gestation of several weeks before postpartum

Etiology is multifactorial including but not limited to the following

• pregnancy associated HTN
• metabolic issues
• autoimmune dysfunctions
• volume overload
• nutritional deficencies

Primary defect is impaired angiogenesis within the myocardium leading to ischemia

Question 8

Iron overload in DCM

Answer 8

Can be caused by overtransfusion of blood or hereditary hemochromatosis

Can cause restrictive cardiomyopathy as well, but this is rare

Question 9

DCM heart morphology

Answer 9

Enlarged and flabby with dilation in all 4 chambers

Also often has mural thrombi present

Ventricular thickness can range from smaller than normal to larger than. Normal

Question 10

DCM histology

Answer 10

Hypertrophied myocytes w/ variable interstitial and endocardial fibrosis (blue staining fibers)

if iron overload is present, hemosiderin (iron) will be present within the cardiac tissue (seen by staining w/ Prussian blue

Question 11

Clinical features of DCM

Answer 11

Ineffective contraction cardinal feature

Cardiac ejection fraction is less than 25%

Mitral regurgitation and lethal arrhythmias may be present

Mural thrombi may occur intracardiac

50% of patients die within 2 years and 35% survive longer than 5 years total
- death is CHF or lethal arrhythmias

Question 12

What other pathology often is associated with DCM?

Answer 12

Progressive CHF

Question 13

Treatment of DCM

Answer 13

Cardiac transplant is the only definitive treatment, however can also use implantation of pacemaker to extend life

Question 14

Arrhythmogenic right ventricular cardiomyopathy

Answer 14

Autosomal dominant disorder that eventually degrades into right-sided HF and arrhythmias

• leads to SCD if not fixed
• also presents with severally thinned right ventricular wall due to myocytes replacement by fat and fibrosis
• cause for 10% of SCDs in athletes*

Question 15

Pathogenesis of arrhythmogenic right ventricular

Answer 15

Caused primarily by mutations in desmosomes junctional proteins and filament desmin

Myocyte death is often caused by desmosomes detachment during strenuous exercise

Question 16

Hypertrophic cardiomyopathy (HCM)

Answer 16

Characterized by the following 4 characteristics:

1) Defective diastolic filling
2) ventricular outflow obstruction
3) myocardial hypertrophy
4) primary diastolic dysfunction

Heart wall becomes thick-walled, heavy and hypercontractile

Question 17

Pathogenesis of HCM

Answer 17

Most cases are caused by missense mutations in genes associated with contractile apparatus
- often transmitted in autosomal dominant pattern

Also, presents w/ gain-o-function mutations in myofilaments function. (This is opposite of DCM where there is a loss-o-function)

• leads to myocyte hyper-contractility
• most common proteins affected are Myosin heavy chains and troponin T

Question 18

Morphology of HCM

Answer 18

Marked massive myocardial hypertrophy w/ NO ventricular dilation

• this thickening is often asymmetrical septal hypertrophy (one side, often the left ventricle, is thicker than the other)
• ventricular cavities compress appear “banana-like” in appearance

Often times plaque buildup occurs in the mitral valve and leads to left ventricular outflow obstruction

Question 19

HCM histology

Answer 19

Marked myocyte hypertrophy w/ haphazard like organization

- also shows interstitial fibrosis throughout the tissue

Question 20

HCM clinical features

Answer 20

Most commonly found in ages of postpubertal growth spurts (15-21)
- can occur at any age though

Characterized by massive left ventricular hypertrophy w/ markedly reduced SV
- 25% of patients have dynamic obstruction to the left ventricle (mitral valve)

Presents with increased pulmonary venous pressure, exertional dyspnea and a very prominent systolic ejection murmurs
- can show with angina as well if ischemia has set in

primary cause of SCD in athletes

Question 21

Possible Clinical issues of untreated HCM

Answer 21

HCM untreated can lead to the following:

• atrial fibrillation
• mural thrombi formation
• ventricular fibrillation
• SCD
• CHF
• IE

Question 22

Treatment of HCM

Answer 22

Pharmacologically by promoting ventricular relaxation
- BBs and CBBs

May need surgery on the mitral valve or the septal muscle if it becomes too prolonged

Question 23

Restrictive cardiomyopathy

Answer 23

Primary decrease in ventricular compliance and impaired ventricular filling during diastole
- this is due to fibrosis of the myocardium due to a variety of causes

Question 24

Causes for restrictive cardiomyopathy

Answer 24

Systemic diseases

Radiation on the heart

Amyloidosis

Sarcoidosis

Metabolism abnormalities

Question 25

3 major forms of restrictive cardiomyopathies

Answer 25

Amyloidosis
- caused by a deposition of extracellular amyloid fibers that produce insoluble B-pleated sheets around myocardium

Endomyocardial fibrosis

• primarily in children and young adults in Africa and other tropical areas
• caused by diffuse fibrosis via nutritional deficiencies of inflammation via parasitic infections
• usually, fibrosis occurs around ventricles, tricuspid or mitral valves
• MOST COMMON form worldwide

Loeffler endomyocarditis

• endocardial fibrosis that often forms large mural thrombi
• caused by hyper-eosinophila and over release of eosinophil granules promoting inflammation and both fibrosis and myocyte death

Question 26

Restrictive cardiomyopathy morphology

Answer 26

Ventricles are normal size and NOT dialated

Atria are both often dilated

Microscopic examination shows variable degrees of interstitial fibrosis
- if amyloidosis, will also show green amyloid proteins