patoloji-ders-notlari

Title

Serdar Balcı

Valvular Heart Diseases, Rheumatic Fever and Endocarditis

Serdar BALCI, MD

VALVULAR HEART DISEASES

Stenosis

Failure of a valve to open completely
Obstructing forward flow
Chronic process
- Calcification or valve scarring

Insufficiency

Failure of a valve to close completely
Regurgitation (backflow) of blood
Caused by:
- Intrinsic disease of the valve cusps
  - Endocarditis
- Disruption of the supporting structures
  - **Aorta, mitral annulus, tendinous cords, papillary muscles, ventricular free wall **
Can be acute or chronic
- Chordal rupture
- Leaflet scarring and retraction

Stenosis and regurgitation

Can occur alone or together
Can involve only one valve
- Mitral valve most common
More than one valve
Murmurs
Outcome depends on:
__ Valve involved__
__ Degree of impairment__
__ Speed of pathology__
__ Effectiveness of compensatory mechanisms__
Sudden destruction of an aortic valve cusp by infection
- Massive regurgitation, abrupt cardiac failure
Rheumatic mitral stenosis
- Progresses over years
- Well tolerated until late in the course

Bicuspid aortic valve

Most common congenital valvular lesion

1-2% of all live births

Mutations Notch signaling pathway

Cusps are of unequal size

**Larger cusp has a midline raphe resulting from incomplete cuspal separation **

Neither stenotic nor incompetent through early life

Prone to early and progressive degenerative calcification

Acquired stenoses

Acquired stenoses of the aortic and mitral valves account for approximately two thirds of all valve disease

Robbins Basic Pathology

Degenerative Valve Disease

Changes that affect the integrity of valvular extracellular matrix (ECM)
Calcifications
- Cuspal in the aortic valve

Calcifications
- Annular in the mitral valve

Calcifications
- Annular in the mitral valve
- Mitral annular calcification usually is asymptomatic unless it grows on the adjacent conduction system

Robbins Basic Pathology

Changes that affect the integrity of valvular extracellular matrix (ECM)
Calcifications
Decreased numbers of valve fibroblasts and myofibroblasts
Alterations in the ECM
- Increased proteoglycan and diminished fibrillar collagen and elastin
- Myxomatous degeneration
- Valve becomes fibrotic and scarred
Changes in the production of matrix metalloproteinases or their inhibitors

Calcific Aortic Stenosis

Most common cause of aortic stenosis

Progressive, age-associated “wear and tear” mechanism

Valvular counterparts to age-related arteriosclerosis

Chronic injury due to:
- Hyperlipidemia
- Hypertension
- Inflammation
- Other factors implicated in atherosclerosis

Most cases
- Asymptomatic, incidentally routine chest X-ray
Severe stenosis
- Require surgery

Calcified masses on the outflow side of the cusps

Protrude into the sinuses of Valsalva

Mechanically impede valve opening

Commissural fusion is not typical
- may become secondarily
Earlier, hemodynamically inconsequential stage
- Aortic valve sclerosis

Concentric left ventricular hypertrophy

Prone to ischemia

Angina can develop

CHF

Cardiac decompensation

Myxomatous Mitral Valve

One or both mitral leaflets are “floppy” and prolapse

Balloon back into the left atrium during systole

0.5-2.4% of adults, one of the most common valvular diseases

Men and women are equally affected

Myxomatous Mitral Valve

Robbins Basic Pathology

Intrinsic defect of connective tissue synthesis or remodeling
Common feature of Marfan syndrome
- Fibrillin-1 mutations
Occurs in other connective tissue disorders
Other connective tissue diseases
- Scoliosis and high-arched palate
Secondary myxomatous change results from injury to the valve myofibroblasts
- Chronically aberrant hemodynamic forces

Ballooning (hooding) of the mitral leaflets
Leaflets
- Enlarged, thick, and rubbery
Tendinous cords
- Elongated, thinned, occasionally rupture
Concomitant tricuspid valve involvement is frequent
- 20-40%
Aortic and pulmonic valves
- Less common

Histologic examination
- Thinning fibrosa layer of the valve
- Expansion of the middle spongiosa layer
- Increased deposition of myxomatous (mucoid) material

The natural history and clinical course are benign
3% develop complications
- Mitral regurgitation
- Congestive heart failure
- Increased risk for infective endocarditis
- Sudden cardiac death due to ventricular arrhythmias

RHEUMATIC VALVULAR DISEASE

Rheumatic Valvular Disease

Rheumatic fever
- Acute
- Immunologically mediated
- Multisystem inflammatory disease
- Occurs after group A β-hemolytic streptococcal infections
  - Pharyngitis
Rheumatic heart disease is the cardiac manifestation
Deforming fibrotic mitral stenosis
The only cause of acquired mitral stenosis
Hypersensitivity reaction
Antibodies cross-reactive with host antigens
M proteins of certain streptococcal strains bind to proteins in the myocardium and cardiac valves
- Injury through the activation of complement and Fc receptor–bearing cells (including macrophages)
CD4+ T cells that recognize streptococcal peptides
- Cross-react with host antigens and elicit cytokine-mediated inflammatory responses
2-3-week delay needed to generate an immune response
Streptococci are completely absent from the lesions
Only 3% of infected patients develop rheumatic fever
- Genetic susceptibility
Chronic fibrotic lesions, healing and scarring
Patients are susceptible to recurrent attacks

Aschoff bodies

Myocardial inflammatory lesions of rheumatic fever
Pathognomonic
Central Necrosis
Collections of lymphocytes (primarily T cells)
Scattered plasma cells
Plump activated macrophages
- Anitschkow cells
- Punctuating zones of fibrinoid necrosis
- Abundant cytoplasm and central nuclei with condensed chromatin
- slender, wavy ribbon (caterpillar cells)

Robbins Basic Pathology

Found in any of the three layers of the heart

Pericardium, myocardium, or endocardium (including valves)

Pancarditis

Pancarditis

Pericardium
- Fibrinous exudate
- Resolves without sequelae
Myocarditis
- Scattered Aschoff bodies within the interstitial connective tissue
Valve involvement
- Fibrinoid necrosis and fibrin deposition along the lines of closure
- 1- to 2-mm vegetations
- Cause little disturbance in cardiac function

Acute rheumatic mitral valvulitis superimposed on chronic rheumatic heart disease

**vegetations (verrucae) **

Previous episodes caused fibrous thickening and fusion

Robbins Basic Pathology

Chronic rheumatic heart disease

Organization of the acute inflammation
Subsequent scarring
- Aschoff bodies replaced by fibrous scar
- Lesions are rarely seen in chronic rheumatic heart disease
Valve cusps and leaflets become permanently thickened and retracted
Mitral valves
- Leaflet thickening
- Commissural fusion and shortening
- Thickening and fusion of the chordae tendineae

Diffuse fibrous thickening and distortion of leaflets

Commissural fusion

Thickening and shortening of the chordae tendineae

Marked left atrial dilation

“fishmouth” or “buttonhole” stenoses

Robbins Basic Pathology

Diffuse fibrous thickening, distortion of the valve leaflets

Commissural fusion

Thickening and shortening of the chordae tendineae

Inflammatory neovascularization

Robbins Basic Pathology

Thickening and distortion of the cusps with commissural fusion

Robbins Basic Pathology

Rheumatic heart disease

Valvular stenosis and regurgitation
- Stenosis predominate
Mitral valve alone → 70%
Combined mitral and aortic → 25%
Tricuspid → less frequently, less severely
Pulmonic valve → almost always spared

Mitral stenosis → Left atrium progressively dilates → Atrial fibrillation → Thrombosis

Mitral stenosis → Left-sided heart failure → Pulmonary vascular and parenchymal changes → Right ventricular hypertrophy and failure

In pure mitral stenosis, the left ventricle is generally normal

ENDOCARDITIS

Infective Endocarditis

Serious infection

Microbial invasion of heart valves or mural endocardium

Destruction of the underlying cardiac tissues

Bulky, friable vegetations composed of necrotic debris, thrombus, and organisms

Aorta, aneurysmal sacs, other blood vessels and prosthetic devices can become infected

Bacteria, Fungi, rickettsiae, chlamydia

Can develop on previously normal valves
Cardiac abnormalities predispose to infections
- Rheumatic heart disease
- Mitral valve prolapse
- Bicuspid aortic valves
- Calcific valvular stenosis
- Prosthetic heart valves (10-20%)
Sterile platelet-fibrin deposits at sites of
- pacemaker lines
- vascular catheters
- damaged endocardium due to jet streams
Host factors
- neutropenia, immunodeficiency, malignancy, diabetes mellitus, and alcohol or intravenous drug abuse

**Streptococcus viridans, normal oral flora → 50-60% **

S. aureus (skin) → 10-20% intravenous drug abusers

HACEK group ( Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella ), oral cavity

Gram-negative bacilli and fungi → rarely

no organism is isolated from the blood (“culture-negative” endocarditis) → 10%

A dental or surgical procedure, transient bacteremia

Intravenous drug users

Occult source from the gut, oral cavity, or trivial injuries

Acute endocarditis
- Destructive infections
- Highly virulent organism attacking a previously normal valve
- Substantial morbidity and mortality even with appropriate antibiotic therapy and/or surgery
Subacute endocarditis
- Low virulence involving a previously abnormal heart
- Scarred or deformed valves
- Protracted course of weeks to months
- Most patients recover after appropriate antibiotic therapy

Acute and subacute forms

Friable, bulky, and potentially destructive vegetations

Fibrin, inflammatory cells, and microorganisms

Aortic and mitral valves are the most common sites of infection

Tricuspid in the setting of intravenous drug abuse

Vegetations may be single or multiple
- May involve more than one valve
- Erode into the underlying myocardium
- Produce an abscess cavity (ring abscess)
Shedding of emboli is common
- Abscesses, septic infarcts, mycotic aneurysms

Subacute endocarditis

Less valvular destruction

Granulation tissue at their bases → suggesting chronicity

Promoting development of chronic inflammatory infiltrates, fibrosis, and calcification over time

Subacute endocarditis caused by Streptococcus viridans on a previously myxomatous mitral valve

Robbins Basic Pathology

**Acute endocarditis caused by Staphylococcus aureus on congenitally bicuspid aortic valve with extensive cuspal destruction and ring abscess **

Robbins Basic Pathology

Nonbacterial Thrombotic Endocarditis

Deposition of small (1-5 mm) thrombotic masses on cardiac valves
Composed mainly of fibrin and platelets
Sterile and nondestructive
Occur in otherwise healthy persons
Diseases associated with general debility or wasting
- Marantic endocarditis
Hypercoagulable states
Hyperestrogenic states
Underlying malignancy
- Mucinous adenocarcinomas
- Procoagulant effect of circulating mucin
- Tissue factor from these tumors
Endocardial trauma
- Indwelling catheter

Can give rise to emboli

Potential nidus for bacterial colonization → infective endocarditis

Robbins Basic Pathology

Autopsy Pathology: A Manual and Atlas

Nonbacterial thrombotic endocarditis

Bland thrombus

No inflammation in the valve cusp or thrombotic deposit

**Thrombus is only loosely attached to the cusp **

Robbins Basic Pathology

Libman-Sacks Endocarditis

Sterile vegetations

Systemic lupus erythematosus

Consequence of immune complex deposition

Inflammation

Fibrinoid necrosis

Subsequent fibrosis and serious deformity

On the valve surface, cords, atrial or ventricular endocardium

Similar lesions occur in antiphospholipid antibody syndrome

Rheumatic heart disease

Small, warty, inflammatory vegetations

Along the lines of valve closure

Substantial scarring

Robbins Basic Pathology

Infective endocarditis

Large, irregular, destructive masses

Extend from valve leaflets onto adjacent structures

Chordae or myocardium

Robbins Basic Pathology

Nonbacterial thrombotic endocarditis

Small to medium-sized, bland, nondestructive vegetations

At the line of valve closure

Robbins Basic Pathology

Libman-Sacks endocarditis

Small to medium-sized inflammatory vegetations

Attached on either side of valve leaflets

Heal with scarring

Robbins Basic Pathology

CARCINOID HEART DISEASE

Carcinoid Heart Disease

Serotonin
Carcinoid tumors (well-differentiated neuroendocrine tumors)
Cardiac lesions occur in massive hepatic metastasis
Endocardium and valves of the right heart are primarily affected
- Pulmonary vascular bed degrades the mediators, left heart is preserved
Left-sided heart carcinoid lesions occur in septal defects, pulmonary carcinoid tumors

Serotonin (5-hydroxytryptamine), kallikrein, bradykinin, histamine, prostaglandins, tachykinins

Glistening, white, intimal plaquelike thickenings on the endocardial surfaces

Smooth muscle cells and sparse collagen fibers embedded in an acid mucopolysaccharide rich matrix

Underlying structures are intact

Tricuspid insufficiency and pulmonary stenosis

Robbins Basic Pathology

Carcinoid heart disease: Microscopic appearance of the thickened intima, which contains smooth muscle cells and abundant acid mucopolysaccharides

Robbins Basic Pathology

Autopsy Pathology: A Manual and Atlas