Pathology: Valvular Heart Disease

Front 1

Discuss VALVULAR DISEASE in general:

Back 1

*Congenital or acquired disorders
*Variable amount of dysfunction

*Stenosis: Failure of valve to open completely with resultant obstruction of forward flow.

*Insufficiency: Failure of valve to close completely with reverse flow.

*Two thirds of all valvular lesions are acquired lesions of the mitral or aortic valves.

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Most Frequent Valvular Lesions:

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*Mitral stenosis (MS) – RHD (rheumatic).

*Mitral insufficiency (MI) – MV prolapse (floppy valve).***

*Aortic stenosis (AS) – calcification.***

*Aortic insufficiency (AI) – dilated aortic root, most commonly due to hypertension and/or aging.


***most common

Front 3

Discuss Calcification in valvular disease:

Back 3

*Calcium deposited in areas of wear and tear.

*Most frequent valve abnormality: aortic valve and/or mitral annulus.

*Bicuspid AV especially prone.

*Lesions also show lipid deposition and resemble atherosclerosis.

Front 4

Discuss Calcific Aortic Stenosis:
risk factors?

Back 4

*Most common cause – aging.

*RHD as cause now less common.

*Congenitally BICUSPID AV is one of the most common associated anomalies.*

*It is prone to calcification and SBE.

*Bicuspid AV associated with CoA (coarctation of aorta), dilated aortic root, and aortic dissection.

*Only in RHD is there likely disease of the MV when AS present.

Front 5

Back 5

*Tricuspid Aortic Valve with Calcification
*"sinuses of Valsalva.
*commissures are free; so that indicates this isn't rhematic valvular disease.

Front 6

Back 6

*Bicuspid Aortic Valve with Calcification
*Raphe is visible (paritally formed third cusp).

Front 7

Discuss Mitral Annular Calcification:

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*Often continuous with calcium deposits in the AV valve cusps.

*Appear as hard, ulcerated nodules.

*Often no impairment of valve function but can be MI or MS.

*Calcification can extend into skeleton and even into conduction system!

Front 8

Back 8

*Mitral Annular Calcification
*Deposits are Ca, lipid, and some inflammatory cells.

Front 9

Back 9

*Mitral annular calcification
*Yellow grainy spot in middle is the calcification.

Front 10

Discuss Mitral Valve Prolapse:

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*Myxomatous ("mucoidy") degeneration. NOT rheumatic in origin.

*Leaflet(s) large, hooded, floppy.

*Serious complications include IE (endocarditis), MR (regurgitation), emboli, arrhythmias. Most patients don't get these complications.

*Leaflets thick and rubbery; chordae elongated; annulus dilated.

*Lamina fibrosa thin; spongiosa thick with myxoid deposits.

Front 11

Causes of MVP?

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*Causes include hereditary disorders of connective tissue such as MARFAN syndrome, a disorder secondary to MISSENSE mutations in the fibrillin gene. It's a small subset of these patients.

*Can also be secondary to degenerative changes in myofibroblasts in response to abnormal hemodynamic forces such as chronic regurgitation.

Front 12

What molecules are more abundant in MVP?

What molecules are decreased?

Back 12

**HE SKIPPED THIS SLIDE**

*Proteoglycans decorin, biglycan, and versican are more abundant in myxomatous valves.

*Expression of the hyaluronan receptor for endocytosis is decreased.

Front 13

Back 13

A. Arrow indicates prolapse of MV leaflet into left atrium, which is dilated.

B. Arrows indicate thrombotic plaques at sites of leaflet-atrium contact. Chordee tendinae are really thin. Fibrin deposition visible (gray-ish).

C. Double arrows indicate "hooding" of MV leaflets; arrow head shows calcification of the annulus.

Front 14

Back 14

Mitral Valve Prolapse (fixed tissue)
*Hooding is visible.
*Thin chordee tendinae, they can eventually rupture.

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Back 15

*MITRAL VALVE PROLAPSE VIEWED FROM LEFT ATRIUM.
*Lumen of valve is visible; valve is pouching into LA.

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Back 16

D. Normal valve (luminal layer-fibrosa; middle-spongiosa; outer-continous with chamber).

E. Myxomatous degeneration of mitral valve. *Pentachrome stain shows abundant proteoglycan deposition (asterisk) in myxomatous area, which is stained blue.

Front 17

Discuss Rheumatic Fever and RHD:

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*Immunologically mediated.

*Presents a few weeks after group A ß-hemolytic strep infection, usually pharyngeal.

*Acute RHD (rare) can be fatal but main problem is due to chronic RHD (progression to valvular dysfunction).

*Deforming fibrosis of *AV and/or MV* may not present clinically until YEARS later.

Front 18

Probable Pathogenesis of RHD:

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*Hypersensitivity reaction induced by group A strep.

*Hypothesis – antibodies against M proteins of streptococci cross-react with glycoproteins in heart and other organs.

Front 19

Evidence for M protein theory of RHD:

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*Hyaluronate in streptococcal wall and human connective tissue is identical.

*Antibodies against streptococci react with sarcolemma.

*Streptococcal M protein shares epitopes with cardiac myosin.

Front 20

Autoimmunity Hypothesis of RHD:

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*Alternative theory.

*Strep M protein a super antigen which activates human T cells expressing genes in the context of class II.

*Susceptibility likely controlled by immune response genes – HLA.

*Helper T cells expressing class II comprise most of cellular infiltrate in valvular lesions.

Front 21

EPIDEMIOLOGY of RHD:

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Front 22

Back 22

*ASCHOFF BODY in RHD; CLASSIC for RHD.

*FIBRINOID necrosis with lymphocytes, plasma cells, macrophages, giant cells, variable numbers of neutrophils and Anitschkow cells.

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Back 23

*ANITSCHKOW CELLS

*Large macrophages with abundant amphophilic cytoplasm and clumped nuclear chromatin which forms a central irregular ribbon resembling a caterpillar.

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Back 24

*ANITSCHKOW CELLS

*Anitschkow cells are often considered pathognomonic for RHD but these are from a 25 year old woman without RHD.

Front 25

RHD Pathology - what do you see in the Endocardium?

Back 25

*Endocarditis – foci of fibrinoid necrosis in cusps or leaflets, usually AV or MV.

*These foci may extend onto chordae tendineae, making them THICK.

*Verrucae (vegetations) along lines of closure of the valves.

*Chronically – you see fibrosis of valve with thick, stiff cusps and/or leaflets.

*Chordae retract, thicken, and fuse.

Front 26

Back 26

*Acute Rheumatic Endocarditis of MV.
*Note verrucae along edges of valve.
*Really rare.

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Back 27

*Acute Rheumatic Valvulitis Superimposed on Chronic Mitral Valvulitis
*Thickened leaflets and thick chordee indicate chronic nature of this RHD.

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Back 28

*Acute Rheumatic Endocarditis
*With verrucae along lines of closure

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Back 29

*Chronic RHD.
*Mitral Stenosis with Diffuse Fibrous Thickening and Commissural Fusion at edges. You would NOT see this fusion in other valvular issues.
*LA opened, looking down into valve.

Front 30

Back 30

*LV looking up to MV.
*“Fishmouth valve” Slit-like lumen of valve showing fibrosis and retraction.

Front 31

Back 31

*RHD – Mitral Stenosis
*Thickened cusps and chordee give away the fact that this is from RHD.

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Back 32

*Healed Rheumatic Aortic Stenosis with Commissural Fusion.
*An extremely distorted AV. Calcified, fibrotic, fused.
*Fusion distinguishes this from calcific aortic stenosis!

Front 33

Discuss Acute Infective (Bacterial) Endocarditis:

Back 33

*Due to highly virulent organisms, e.g. Staphylococcus aureus.

*Acute BE can affect previously NORMAL valves.

*Risk of septic (bug-containing) emboli.

*Risk of perforation of cusp or leaflet with acute regurgitation.

Front 34

What is Infective Endocarditis?

Back 34

*Colonization with or without invasion of the endocardium, not always on a valve.

*Often destruction of underlying tissue.

*Vegetations consist of the offending agent and thrombotic debris.

*Vegetations may set up on prostheses.

*May be associated with infective arteritis.

Steps:
1) Injured endothelium
2) Fibrin/platelet adhesion
3) Bacterial vegetation of adhesion

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Back 35

*Acute Bacterial Endocarditis with Larger Fungating Lesions.
*Huge vegetation.

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Back 36

*Acute Endocarditis of Congenital Bicuspid Aortic Valve (S. aureus...he says bicuspid AV is "probably" more likely to get infected).
*Cusps are pretty much destroyed. Arrow indicates beginning of a ring abscess forming.

Front 37

Discuss Subacute Bacterial Endocarditis (SBE):

Back 37

*Organisms of lesser virulence (strep viridans) at sites of endothelial injury, e.g. PREVIOUSLY DEFORMED valves or impact of high velocity flow.

*May smolder and present after months.

*Risk of septic emboli.

*Less destruction of underlying tissue than in acute BE.

*Evidence of HEALING.

**GUSTAV MAHLER HAD STREP VIRIDANS SBE**HISTORY LOL

Front 38

Back 38

*SUBACUTE BACTERIAL ENDOCARDITIS OF MITRAL VALVE
*Can't tell this is subacute just by the pic. Lots of vegetations visible.

Front 39

Back 39

*Subacute Endocarditis Mitral Valve (S. viridans)
*Can't tell subacute just by looking grossly.

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Back 40

*SUBACUTE BACTERIAL ENDOCARDITIS (AORTIC VALVE).

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Back 41

*Infective Endocarditis
*pink = firbin
*blue = WBCs

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Back 42

*SBE – Aortic Valve

*S. Viridans produced a large, crumbling lesion on an aortic cusp scarred by RHD.

*A layer of platelets and fibrin is covered by a layer of mononuclear cells.

*A granular mass of S. viridans is enclosed centrally.

*Blue lymphoid looking tiny dots = bacteria

Front 43

Back 43

*Endocarditis due to Candida (you can't tell)
*Point is, you can get IE from lots of things.
*Immunosuppressed patient with a huge vegetation.

Front 44

Back 44

*Infective Endocarditis
*Yellow = large vegetation with destruction of chordae.

Front 45

Complications of IE:

Back 45

*Valvular stenosis or insufficiency

*Abscess in annulus or myocardium

*Suppurative pericarditis

*Paravalvular leak (prosthesis)

*Emboli

*Focal and diffuse glomerulonephritis due to antigen-antibody complexes.

Front 46

Back 46

*Healed Endocarditis of Mitral Valve.
*Valve is distorted.
*You can see past perforation of the valve on the right.

Front 47

Discuss Nonbacterial Thrombotic (MARANTIC) Endocarditis (NBTE):

Back 47

*Occurs in debilitated patients.

*Deposition of small noninfected, loosely attached masses of fibrin, platelets, and other blood components on valves.

*Often associated with hypercoagulable state, as in mucinous adenocarcinoma.

*Histology – bland thrombi; no inflammation or valve damage.

Front 48

Back 48

*Nonbacterial Thrombotic (marantic) Endocarditis of Mitral Valve.
*Looking along the lines of closure of the MV.
*Arrows = verrucae
*µscopic view shows fibrin, lymphocytes, inflammatory cells.

Front 49

Back 49

*NBTE – Mitral Valve
*Vegetations along line of closure
*Thrombus adherent to intact leaflet

Front 50

Back 50

*Nonbacterial Thrombotic (Marantic) Endocarditis
*Note pattern of vegetations.

Front 51

Discuss Libman-Sacks Endocarditis:

Back 51

*Seen only in SLE!

*Small verrucae.

*Necrotic vascular tissue and fibrin with macrophages, lymphocytes, and PCs.

*May be intense inflammation in underlying tissue.

*Mitral Valve most often affected.

***LIBMAN WAS MAHLER'S DOCTOR*** HISTORY!!!!!!111

Front 52

Back 52

*Libman-Sacks Endocarditis
*Distribution of vegetations is key to identifying the different endocarditis's on the boards.

Front 53

Back 53

*LIBMAN-SACKS ENDOCARDITIS
*Note vegetative pattern along lines of closure.

Front 54

Discuss endocarditis in Carcinoid Syndrome:

Back 54

*Fibrous PLAQUE-LIKE endocardial thickening on walls of chambers or valves.
*Lesions usually on RIGHT SIDE of heart.
*Lesions composed of smooth muscle and collagen in a mucopolysaccharide matrix.
*Carcinoid tumors secrete SEROTONIN.
*Lesions correlate with plasma levels of 5-HT.
*Lesions on left side if carcinoid tumors are in lung.

Front 55

Back 55

L: Endocardial Fibrosis and thickening of Right Ventricle and Tricuspid Valve (Carcinoid syndrome).

R: Movat Stain with Acid Mucopolysaccharide Areas Stained Blue; lots of MPS deposition.

Front 56

Discuss Prosthetic Heart Valves:

Back 56

*Mechanical
-Non-physiological biomaterials with caged balls, tilting discs, or hinged semicircular flaps

*Tissue (Bioprosthetic)
-Chemically-treated animal tissue mounted on a frame

Top left: ball and cage valve
top middle: disc valve
bottom left: bileaflet valve
other two are porcine.

Front 57

Complications from prosthetic valves:

Back 57

*Thromboembolism
*Structural deterioration
*Overgrowth of fibrous tissue
*Hemolysis due to shearing forces
*Improper placement or disproportionate size
*Prosthetic valve endocarditis

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Back 58

*Thrombosed pivoting disc, Valve prosthesis. This killed the patient.

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Back 59

*Prosthetic mitral valve with a strut (arrow) causing partial obstruction of the left ventricular outflow tract

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Back 60

*Calcification and Tear of Prosthetic Porcine Valve.
*Analogous to calcific aortic stenosis.