Valvular Disease and Endocarditis
Valvular Disease results in Stenosis, Insufficiency, or both
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 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
Histological layers of Valves:
- 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
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
- (1) Ventricularis (aortic)/Auricularis (mitral)
- (2) Spongiosa
- (3) Fibrosa
- (4) arterialis
Closing edge: area where overlapping and non-overlapping portions of valve meet
- free edge free portion of the valve not in contact with the opposite leaflet
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
- closing edge portion of the valve in contact with the opposite leaflet
Major Causes of Acquired Heart Valve Disease
Mitral Valve Disease
Postinflammatory Scaring (rheumatic heart disease)
Abnormalities of leaflets and commissures (Intrinsic)
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
- Mitral Stenosis (Intrinsic)
Postinflammatory Scaring (rheumatic heart disease)
Senile calcific aortic Stenosis
Calcification of congenitally deformed valve
Intrinsic Valvular disease
Postinflammatory Scaring (rheumatic heart disease)
Aortic Disease (Structural)
Degenerative aortic dilation
- Aortic Stenosis (Intrinsic)
Valvular Diseases Classified by Type of Valvular Dysfunction
(1) Mitral Valve Prolapse (Myxomatous Degeneration of the Mitral Valve): special form of regurgitation
: 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 .
(2) Insufficiency/ Regurgitation
: 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:
- 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
: 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)
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)
- (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
(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)
- 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.
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:
- Sequela of Rheumatic fever following Group A (
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
- 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 (
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.
- 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.
Þ permanent deformity.
- Characterized by organization of the acute inflammation and subsequent deforming fibrosis.
- Gross: Valve leaflets become thickened and retracted
Micro: diffuse fibrosis and often neovascularization that obliterates the layered avascular leaflet architecture.
- 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.
Chronic Rheumatic Heart disease: most frequent cause of mitral Stenosis (99% of cases)
- Aschoff bodies are replaced by fibrous scars.
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.
- 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
Endocarditis cause of cardiac valvular insufficiency; formation of vegetations on the endocardium
(1) Infective Endocarditis due to colonization or invasion of endocardium of the cardiac valves by microorganisms
- (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)
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
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
(Pericarditis) Þ serofibrinous exudate which may be localized or generalized ("bread and butter")
- 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
Myocardium Þ focal interstitial inflammatory lesions; characterized by the pathognomonic Aschoff Nodule and diffuse interstitial myocarditis
- Long Term Sequelae: organization and healing of pericardial inflammation exudate leads to diffuse pericardial fibrosis with obliteration of the pericardial sac and pericardial space
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
- may injure the myocytes directly or damage the conduction system
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
- 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
Prognosismild disease may heal by resolution and inflammatory changes disappear without permanent cardiac damage
- cardiac lesions are usually sterile
- very small
- outflow surface of leaflets
- mitral valve effected more often then aortic
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)
- 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
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
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
- both causes result in rigidity of the cusps and stenosis of the valve origin
ß oxygen supply or compromised microcirculation in the myocardium due to hypertrophy may occur
- Long Term Sequelae: chronic heart failure is most serious
- Angina or syncopal attacks due to
Valvular Insufficiency and Regurgitation
Definition failure of a valve to close completely, therefore allowing retrograde flow
Cause Intrinsic Þ vegetation; ulceration; perforation; stenosis
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
- stenosis and insufficiency often coexist in the same valve, but one defect often predominates
- prolapse is a paradoxical backward movement of the valve cusps
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 Marfans 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
- "Floppy Valve" Primary Myxoid Degeneration most common cause of valvular insufficiency