Valvular Disease and Endocarditis

Valvular Disease – results in Stenosis, Insufficiency, or both

Stenosis is the failure of a valve to open completely, thereby impeding forward flow.

Insufficiency (a.k.a. regurgitation or incompetence) caused by incomplete valve closure, allowing a reversed flow.

A complication of insufficiency is Prolapse = the paradoxical backward movement of valve cusps or leaflets

*Functional regurgitation results from ventricular dilation Þ papillary muscles pull ß and outÞ incomplete closure

Cause may be acquired or congenital (acquired Stenosis of mitral and aortic valves account for 2/3 of lesions)

Stenosis: almost always due to primary cuspal (intrinsic) abnormality and is virtually always from a chronic process

Insufficiency: due to intrinsic abnormalities; or *structural damage or distortion of valvular support structures

Histological layers of Valves:

(1) Ventricularis (aortic)/Auricularis (mitral)
(2) Spongiosa
(3) Fibrosa
(4) arterialis

Anatomy

valve components – lined with endothelium; dense collagenous core (fibrosa); loose connective tissue (spongiosa)

Annulus is rim of valve that attaches valve to heart and major vessels.

Free edge of leaflet: is far edge of valve

free edge – free portion of the valve not in contact with the opposite leaflet

Closing edge: area where overlapping and non-overlapping portions of valve meet

closing edge – portion of the valve in contact with the opposite leaflet

Valve Development

leaflets form from 3 embryonic buds

bicuspid valves Þ one of the leaflets do not from and one of the forming leaflets compensates by becoming larger; this larger leaflet contains a median raphe where the leaflet should have formed

Major Causes of Acquired Heart Valve Disease

Mitral Valve Disease

Mitral Stenosis (Intrinsic)

Postinflammatory Scaring (rheumatic heart disease)

Mitral Regurgitation

Abnormalities of leaflets and commissures (Intrinsic)
Postinflammatory Scaring
Infective endocarditis
Mitral valve Prolapse
Abnormalities of tensor apparatus (Structural)
Rupture of papillary muscle
Papillary muscle dysfunction (fibrosis)
Rupture of chordae tendineae
Abnormalities of the left ventricular cavity and or annulus (Structural)
Left ventricular enlargement (myocaeditis, dilated cardiomyopathy)
Calcification of mitral annulus

Aortic Valve Disease

Aortic Stenosis (Intrinsic)

Postinflammatory Scaring (rheumatic heart disease)
Senile calcific aortic Stenosis
Calcification of congenitally deformed valve

Aortic Regurgitation

Intrinsic Valvular disease
Postinflammatory Scaring (rheumatic heart disease)
Infective endocarditis
Aortic Disease (Structural)
Degenerative aortic dilation
Syphilitic aortitis
Ankylosing spondylitis
Rheumatoid arthritis
Marfan Syndrome

Valvular Diseases Classified by Type of Valvular Dysfunction

(1) Mitral Valve Prolapse (Myxomatous Degeneration of the Mitral Valve): special form of regurgitation

due to inborn error of metabolism (associated with Marfans Syndrome)Þ ß tensile strength of leaflets and chordae tendini Þ billowing leaflets Þ snap up into atria during systole making systolic click. Can progress to regurgitation (murmur)

affects 3-7% of US adults; mostly women (6:4). If it becomes symptomatic, patients usually present between 20-40 yo.

3% of MVP patients develop:

(1) Infective endocarditis
(2) Mitral insufficiency

(3) Stroke or other infarct, or
(4) Arrhythmias

Gross

Intrinsic abnormalities: Intercordal ballooning (hooding) of mitral leaflets, which are often thick and rubbery.

Annular dilation is characteristic (rare in other causes of mitral insufficiency).

Support structure abnormalities: often tendinous cords are elongated, thinned, and occasionally ruptured. Webbing

Normal Commisures (fusion is seen in Rheumatic heart disease)

Micro

Myxoid degeneration: focal thickening of the spongiosa layer with deposition mucoid (myxomatous) material and degeneration of the fibrous layer on which the structural integrity of the leaflet depends. Collagen of cords is also ß .

Disorganization

(2) Insufficiency/ Regurgitation

Intrinsic Abnormalities: perforations or holes, ulcerations, vegetative growths

Support structure abnormalities: disruption of annulus (stretching due to Ý pressures), chordae tendini fusion, papillary muscle dysfunction caused by MI.

Endocarditis is the # 1 cause of Aortic and Mitral Insufficiency. The following forms of endocarditis cause insufficiency:

(a) Infective Endocarditis: Serious! usually bacterial; creates large (few cm) vegetations of thrombotic debris and organisms

Covers and causes destruction to outflow track: valves, mural endocardium. Grows on free edge and chordae tendini

On normal and abnormal valves; left > right; lack of circulation to valves makes it hard for antibiotics to work on them.

Gross: large friable bulky vegetations; can emboli and cause septic infarcts. Can cause ulcerations, perferations, abscess etc. These complications are rare in the other forms of endocarditis.

Micro: sub-acute Þ granulation tissue base. Eventually fibrosis, calcification and chronic inflammatory infiltrates.

(b) Thrombotic Vegetation (Nonbacterial Thrombotic Endocarditis-NBTE):these vegetations are STERILE! and small (1-5mm)

outflow surface of leaflets are affected by deposition of fibrin and blood elements from an underlying disease.

Gross: Forms along the line of closure; valves are usually normal; and right side is affected as much as left.

Micro: bland thrombus without accompanying inflammation reaction or induced valve damage.

(c) Libman-Sacks Endocarditis (Endocarditis of SLE) Most common of the CT disease that cause this. This was FYI.

Rheumatic Heart Disease (causes stenosis (see #3 below) as well as insufficiency; causes 99% of mitral stenosis)

Sequela of Rheumatic fever following Group A (b -hemolytic) streptococcal pharyngitis

Inflammatory and healing reaction to repeated immunological injury- probably a hypersensitivity reaction

Probably Ab against M protein of some strains of strep crossreact with glycoproteins in heart, joints and other tissues.

This leads to cellular immunity as well.

(a) Acute Rheumatic Fever is one of the only things that leads to Pancarditis. This stage can result in Insufficiency. Pancarditis involves inflammation of entirity of any of the three layers of the heart:

Pericardium: Fibrinous pericarditis – fibrinous or serofibrinous pericardial exudate (bread and butter pericarditis).

Myocardium: Myocarditis: deposition of immune complexes leads to inflammatory lesions that are distinctive in the heart = Aschoff bodies: foci of fibrinoid necrosis surrounded by lymphocytes (primary T cells)

Can see plasma cells and plump macrophages called Anitschow cells (pathognomonic for rheumatic fever).

Antischow cells have abundant amphophilic cytoplasm and central round to ovoid nuclei with the chromatin in a central, slender wavy ribbon (Þ the name caterpillar cells) Large multi nucleated = Aschoff giant cells.

Myocarditis may cause cardiac dilation that may evolve to mitral valve insufficiency or heart failure.

Endocardium: Involvement of outflow track and left valves by inflammatory foci Þ fibrinoid necrosis of cusps or cords

Vegetations sit on top of these along the line of closure.
Have "bread and butter" appearance (irregular wart projections); probably result from precipitation of fibrin at sites of erosion related to underlying inflammation and fibrinoid degeneration.

Main threat to life is acute heart failure due to myocardial inflammation or arrhythmia due to damage to conduction.

(b) Chronic Rheumatic Heart disease: as already mentioned, causes both insufficiency and stenosis.

Characterized by organization of the acute inflammation and subsequent deforming fibrosis.

Gross: Valve leaflets become thickened and retracted Þ permanent deformity.

Mitral valve is almost always involved but clinical significance results when aortic is affected
Additionally there is commissural fusion; thickening, shortening and fusion of the tendinous cords.

Micro: diffuse fibrosis and often neovascularization that obliterates the layered avascular leaflet architecture.

Aschoff bodies are replaced by fibrous scars.

(3) Stenosis

Chronic Rheumatic Heart disease: most frequent cause of mitral Stenosis (99% of cases)

65-70% of cases solely involve the mitral valve. 25% involve mitral and aortic. Similar but less severe involvement of tricuspid possible; pulmonary involvement rare.

Fibrous bridging across the valvular commissures and calcification create fish mouth or button hole Stenosis.

Tight mitral Stenosis Þ dilation of left atrium Þ mural thrombosis.

Long standing congestion Þ to pulmonary changes Þ right ventricular hypertrophy. LV is normal in mitral Stenosis.

Valvular degeneration caused by Calcification

Acquired aortic Stenosis is consequence of wear and tear (repeated bendingÞ stiffening like with polymers in credit card)

Dystrophic calcification with less lipid deposition and cellular proliferation than atherosclerosis but still similar

3 Types: (1) senile calcific aortic stenosis, (2) congenitally bicuspid aortic calcification, (3) mitral annular calcification

Senile (70-80yo) and Congenitally bicuspid (50-60 yo) aortic calcification involve the same process which accelerates in the bicuspid because wear and tear is spread over 2 valves instead of 3. Commissures are the points along the annulus where the leaflets meet and were buds from which the leaflets separated embryologically. Congenital bicuspid valves result from one of 3 buds not forming and a raphe forming where the leaflets would have separated.

Characterized by heaped up calcified masses within the aortic cusps that ultimately protrude through the outflow surfaces into the sinuses of valsalva Þ preventing the opening of the cusps.

Begins within the valvular fibrosa at point of maximum flexure (margins of attachment), distorting architecture at base.

Free edges not involved, commissural fusion is absent, mitral valve spared. (Contrast to rheumatic aortic Stenosis).

Mitral annular calcification: stony, hard, sometimes ulcerating nodules of Ca build up along annulus behind leaflet.

Normally does not affect function but can affect AV conduction if Ca penetrated too far, can cause insuff or Stenosis.

Appears mostly in women > 60 yo.

Endocarditis – cause of cardiac valvular insufficiency; formation of vegetations on the endocardium

Types

(1) infective (bacterial or fungal)
(2) thrombotic (marantic),
(3) rheumatic (due to rheumatic heart disease)
(4) Libman-Sacks (due to connective tissue disease such as systemic lupus erythematosus)

(1) Infective Endocarditis – due to colonization or invasion of endocardium of the cardiac valves by microorganisms

large

found on outflow surface of leaflet; along free margin

on normal or abnormal valves

endocarditis found on left side of the heart more frequently than the right

high virulent organisms Þ destructive, rapidly progressive and may be fatal

low virulent organisms Þ insidious, follows a protracted course and may resolve without dysfunction

(2) Thrombotic (Marantic) Endocarditis

sterile
small
outflow surface of leaflets

found along line of closure

found on normal or abnormal valves

right valve = left valve

fusion of the chordae tendinae

(3) Rheumatic Heart Disease

Definition Rheumatic heart disease follows rheumatic fever which is an acute, immunologically mediated, multisystem inflammatory disease that occurs a few weeks after an episode of Group A streptococcal pharyngitis and often involves the heart.

Etiology sequelae of rheumatic fever; not a direct infection; inflammation or healing reaction to repeated immunologic injury Þ antistreptococcal Ab cross reacting with cardiac tissue, cardiac Ab or cellular immunity

Histology characterized by inflammatory changes involving all portions of the heart - epicardium, myocardium and endocardium Þ pancarditis

Epicardium (Pericarditis) Þ serofibrinous exudate which may be localized or generalized ("bread and butter")

Long Term Sequelae: organization and healing of pericardial inflammation exudate leads to diffuse pericardial fibrosis with obliteration of the pericardial sac and pericardial space

Myocardium Þ focal interstitial inflammatory lesions; characterized by the pathognomonic Aschoff Nodule and diffuse interstitial myocarditis

may injure the myocytes directly or damage the conduction system

Endocardium Þ – valvulitis; inflammatory infiltration and edema in the stroma of the valves with superimposed presence of rheumatic vegetations, small bead-like projections on the atrial surfaces of the atrio-ventricular valves and on the ventricular surface of the aortic valve

pulmonic valve is rarely involved

Long Term Sequelae: organization and healing of acute inflammatory lesions leads to scarring and vascularization of the cusps and leaflets Þ leads to adhesions between the cusps and leaflets

thickening, shortening and fusion of the chordae tendineae

valve rigidity and stenosis of the valve orfice

Gross Anatomy

cardiac lesions are usually sterile
very small
outflow surface of leaflets

mitral valve effected more often then aortic

Prognosis–mild disease may heal by resolution and inflammatory changes disappear without permanent cardiac damage

most episodes of acute rheumatic heart disease heal by organization with permanent cardiac damage

recurrent attacks of rheumatic fever with accompanying carditis are very common and additional injury may occur

arrhythmias may arise from damage to the conducting tissues Þ major threat to life

acute rheumatic inflammatory infiltration of myocardium can inhibit the contractile properties of the heart Þ CHF

Chronic Rheumatic Disease (not "chronic rheumatic fever") – pathologic status of the heart created by previous cardiac insults; no inflammatory state

Epidemiology – nonrheumatic cardiac heart disease is now the most common valvular disease; rheumatic disease was the most common valvular disease 30 years ago when rheumatic fever was more common

Chronic Rheumatic Valvular Disease

Gross Anatomy Þ "fishmouth" deformity; leaflet thickening and fibrosis

Symptoms – fever; malaise; cardiac murmurs may be present with left-sided vegetations, but probably relate more to the pre-existence of a cardiac anomaly predisposing to endocarditis than to the endocarditis itself

Complications – valvular insufficiency or stenosis; cardiac failure; thromboembolization with visceral infarction; metastatic infection (infective endocarditis)

Aortic Stenosis

Etiology – dystrophic calcification of a congenitally bicuspid valve or senile calcification of a normal tricuspid valve in old age are the most common forms of aortic valve stenosis

both causes result in rigidity of the cusps and stenosis of the valve origin

Gross Anatomy - calcifications are usually nodular, found either within the cusps themselves or along the line of closure and protrude into the sinuses of Valsalva

Long Term Sequelae: chronic heart failure is most serious

Angina or syncopal attacks due to ß oxygen supply or compromised microcirculation in the myocardium due to hypertrophy may occur

Valvular Insufficiency and Regurgitation

Definition – failure of a valve to close completely, therefore allowing retrograde flow

stenosis and insufficiency often coexist in the same valve, but one defect often predominates
prolapse is a paradoxical backward movement of the valve cusps

Cause – Intrinsic Þ vegetation; ulceration; perforation; stenosis

Support Structures Þ dilation or rigidity of annulus; chordae tendinae or papillary muscle abnormalities

Mitral Valve Prolapse

Etiology: may be due to congenital anomalies, dystrophic calcification of annulus or due to an inflammatory disease

"Floppy Valve" – Primary Myxoid Degeneration – most common cause of valvular insufficiency

Floppy Valve – myxoid degeneration leading to a ß in tensile strength of the connective tissue of the valve; results in stretching, elongation and enlargement of all valve structures

chordae tendineae become elongated and attenuated forming a web or mesh on the ventricular surface of the leaflet Þ may rupture

interchordal hooding (or ballooning) of the leaflets between the points of attachment of the chordae tendineae

Histologically – severe myxoid degeneration in the valves with pools of myxoid material disrupting or destroying the normal layered valve architecture

Etiology – unknown; regarded as a congenital anomaly and may be related to other connective tissue diseases such as Marfan’s syndrome

Epidemiology – extremely common; 5-10% of the general population in the US; Men:Women – 4:6; first detected in 20-40 year olds

Clinical – mid-systolic click corresponding to opening of the prolapsed mitral valve leaflets in the left atrium