Pathology of Valvular Heart Disease

Question 1

What are the three layers of normal valves (aside from the endothelial covering? What layer faces the highest stress portion (i.e. would face venticular side in AV valves and large vessel side in semilunar valves)

Answer 1

1. Fibrosa - dense collagen layer to which supporting structures attach (chordae tendinae) -> face high stress portion
2. Spongiosa - central core of loose connective tissue with proteoglycans
3. Elastin-rich layer - on inflow surface (atrialis or ventricularis)

Question 2

What type of murmur is caused by an incompetent mitral valve or stenotic aortic valve?

Answer 2

Systolic murmur

Question 3

What type of murmur is caused by narrowed mitral valve or incompetent aortic valve?

Answer 3

Diastolic murmur

Question 4

What is the most common cause of a murmur, and what processes allow this to develop?

Answer 4

A valvular stenosis, most commonly on aortic then mitral valves

• > usually due to calcification or chronic scarring (due to chronic rheumatic heart disease)
• > gradual onset

Question 5

How can valvular insufficiency arise gradually or suddenly?

Answer 5

Gradually - myxomatous degeneration of mitral valve, ventricular cavity enlargement, dilatation of pulmonary or aortic root

Suddenly - infective endocarditis (hole appears), acute rheumatic heart disease, chordae tendinae or papillary muscle rupture

Question 6

What valve is most likely involved in dystrophic calcification, and who is most susceptible? How does this appear?

Answer 6

Aortic valve -> highest pressures

Most susceptible = congenitally bicuspid - appears with two cusps of unequal size, larger one containing a midline raphe

Question 7

How can stenosis from dystrophic calcification be told from stenosis due to chronic rheumatic heart disease?

Answer 7

Dystrophic - commissures will be intact, calcifications extend into base of valve into sinuses of Valsalva

Chronic rheumatic heart disease - affects mitral valve much more than aortic, and appears with fishmouth / buttonhole appearance - thickening and distortion of valve leaflets / cusps with commissural fusion

Question 8

How will patients with calcific valvular degeneration present and why?

Answer 8

Present with angina -> due to compensatory LV hypertrophy and ischemia

Syncope -> decreased cardiac output

Question 9

What are the potential complications of mitral annular calcification?

Answer 9

Dysfunction of valve -> stenosis or insufficiency

Arrhythmias -> if calcifications enter into the endocardium

Superimposed thrombosis and infectious endocarditis -> turbulent blood flow injures endothelium

Question 10

How does it sound to auscultate a mitral valve prolapse? What accounts for this sound?

Answer 10

Midsystolic click, typically heart in young women

Due to long, thin chordae tendinae snapping against the wall during systole

Question 11

What typically causes mitral valve prolapse (microscopically) and what are the etiologies of this?

Answer 11

Myxomatous degeneration of mitral valve -> dilated valvular annulus with enlarged, thick, rubbery leaflets due to thick loose connective tissue in spongiosa layer of valve (and loss of collagen in fibrosa layer + chordae tendinae)

-> cause usually unknown, but sometimes due to connective tissue diseases such as Marfan syndrome

Question 12

What secondary changes often occur in mitral valve prolapse?

Answer 12

Friction-induced fibrosis of left atria, with possible thrombi in left atria (due to leaflets hitting endocardium of left atrium)

Friction induced fibrosis of LV endocardium (due to chordae tendinae snapping against the walls of LV)

Question 13

What are same of the complications of mitral valve prolapse?

Answer 13

Mitral valve insufficiency -> will not always occur w/prolapse

Associated w/ all valve disease: Systemic thromboembolism, infective endocarditis

Question 14

What is the pathogenesis of rheumatic heart disease? What type of infection does it follow?

Answer 14

Immune-mediated reaction generated in response to group A S. pyogenes pharyngitis only (not following skin infection)

Antibodies to M protein of S. pyogenes cross-reactive with cardiac myosin

Question 15

What does acute rheumatic heart disease cause overall and what will be seen microscopically in the myocardium?

Answer 15

Pancarditis (all layers of heart)

Aschoff bodies - foci of swollen, degenerated collagen with lymphocytes, plasma cells, macrophages (chronic inflammatory).

Macrophages -> Anitschkow cells - “caterpillar” - condensed, elongated nuclear chromatin

Question 16

What does acute rheumatic heart disease do to the pericardium?

Answer 16

Causes fibrinous pericarditis

-> friction rub due to Aschoff bodies

Question 17

What does acute rheumatic heart disease do to the endocardium? What side of the heart does it affect?

Answer 17

Small, sterile thrombi (vegetations) along lines of closure of valves

Affects especially left side of heart, mitral > aortic valve.

Question 18

What is the pathophysiology of chronic rheumatic heart disease?

Answer 18

Neovascularization of heart valves with fibrotic valular deformities

Valvular stenosis of mitral > aortic valves: thickening and distortion of valves with commissural fusion.

Thickening, fusion, and shortening of chordae tendinae (look like tree trunks)

Question 19

What antibodies can be tested for to detect acute rheumatic fever?

Answer 19

ASO - anti-Streptolysin O

Anti-Streptococcal DNAse B

Question 20

What are the JONES criteria? Who does J affect more? Why does S happen?

Answer 20

J - migratory polyarthritis of joints (especially adults)
O - acute pancarditis
N - Subcutaneous nodules
E - Erythema marginatum (redder on margins)
S - Sydenham chorea - due to crossreactivity with BG

Question 21

What are the potential complications of chronic rheumatic heart disease?

Answer 21

Left sided valvular stenosis -> cardiac hypertrophy and/or dilatation -> arrhythmias, thromboembolic events, IE, and CHF

Question 22

What arrhythmia commonly occurs as a result of chronic rheumatic heart disease?

Answer 22

Atrial fibrillation -> secondary to dilatation of left atrium due to mitral valve stenosis

Question 23

What are some predisposing factors to infective endocarditis?

Answer 23

1. Pre-existing valvular pathology
2. Abnormal intracardiac jet streams -> cause turbulent blood flow
3. Decreased immunity
4. Portals of entry (indwelling catheters, IV drug use)

Question 24

What causative pathogen of IE is associated with GI and liver diseases, especially carcinoma of colon?

Answer 24

Streptococcus bovis

Question 25

What is the most common cause of IE in IV drug users?

Answer 25

S. aureus, especially in right-sided heart (only time this really happens since its normally left-sided valves which are injured)

Question 26

What is the most common cause of IE on previously diseased valves?

Answer 26

S. viridans -> dental bacteremia

Question 27

What is the most common cause of IE on prosthetic heart valves?

Answer 27

Coag-negative staph

-> S. epidermidis

Question 28

How does IE appear grossly and microscopically?

Answer 28

Grossly - usually left-sided, bulky vegetations with destruction / perforation of valve leaflets / cusps

Microscopically - aggregates of acute inflammatory cells, microorganisms, fibrin, platelets (thrombus protects bacteria)

Question 29

What are the local effects of infective endocarditis?

Answer 29

Valvular regurgitation -> due to perforation

Changing cardiac murmur / separation of prosthetic valve -> due to abscess formation

Question 30

What is Marantic Endocarditis also called and what are the usual causes? Will there be inflammation?

Answer 30

Nonbacterial Thrombotic Endocarditis (NBTE)

• > Hypercoagulability state associated with debilitating disease like malignancies (especially mucinous adenocarcinoma of pancreas)
• > endocardial injury, often due to intracardiac catheter

Marantic = Marasmus

Only endocarditis w/o significant inflammation

Question 31

What are the gross and microscopic features of NBTE, and its primary complication?

Answer 31

Gross - small vegetations along lines of valve closure WITHOUT inflammatory valve destruction

Microscopic - Sterile thrombotic material loosely attached to valve surface

Complication - Systemic thromboembolic -> infarcts

Question 32

What causes Libman-Sacks Endocarditis and how is it distinguished from other sources of endocarditis? Include how it appears grossly?

Answer 32

Associated with SLE

Grossly: Vegetations can be found on both sides of the valves (rather than just inflow surfaces like others), and on chordae tendinae. Can even appear on endocardial lining

Question 33

How does Libman-Sacks endocarditis appear microscopically and what are its potential complications?

Answer 33

Aggregates of thrombotic material adhering to subendocardial fibrinoid necrosis, associated with inflammation

Complication: Fibrotic valvular deformities

Question 34

What condition is characterized by systemic flushing, diarrhea, and wheezing, with thickened endocardium due to accumulation of mucopolysaccharide-rich matrix containing smooth muscle cells? What side of the heart does this affect and why?

Answer 34

Carcinoid heart disease -> part of carcinoid syndrome in some neoplasms, due to ectopic serotonin production

Affects the right side of the heart only, since serotonin from venous circulation is broken down in the lungs

Question 35

What are the pro’s and con’s of mechanical and bioprosthetic valves?

Answer 35

Mechanical: Pros - longer-lived, Cons - need anticoagulation

Bioprosthetic valves - Pros: No anti-coag, Cons: shorter lifespan, tear easily

Question 36

Other than thrombosis / endocarditis, which is a strange complication of mechanical valves?

Answer 36

Chronic hemolysis -> shearing of red cells on the way thru the valve due to abnormal tissue-prosthesis interface.