Rheumatic Fever and Heart Disease

• Definition: rheumatic fever is an acute, immunologically mediated, multi-system inflammatory disease that follows, after a few weeks, an episode of group A streptococcal pharyngitis (3% of patients).

• The incidence and mortality of rheumatic fever has declined over the past 30 years (due to improved socioeconomic condition and rapid diagnosis and treatment of strep. pharyngitis.

Rheumatic Fever: Heart

• Affect the heart during its acute phase acute rheumatic carditis.

• Cause chronic valvular deformities (many years after the acute disease.

Pathogenesis and Key Morphologic Changes of Acute Rheumatic Heart Disease

Hypersensitivity reaction induced by group A strept. (ab. Against protein M

Cross-reaction /

Autoimmune response

Morphology: Acute Rheumatic Fever

• Inflammatory infiltrates occur in a wide range of tissues: synovium, joints, skin, heart.

• Focal fibrinoid necrosis mixed inflammatory reaction (diffuse or localized) Fibrosis (chronic rheumatic heart disease) .

Acute Rheumatic Carditis

• Pancarditis (endo- myo- pericarditis).• Multiple foci of inflammation within the connective

tissue of the heart. (Aschoff bodies: central fibrinoid necrosis, surrounded by chronic mononuclear inflammatory infiltrate and occasional large histiocytes).

• Diffuse interstitial inflammatory infiltrates (may lead to generalized dilation of the cardiac chambers).

Acute Rheumatic Carditis• Pericardial involvement: fibrinous pericarditis,

sometime associated with serous or serosanguinous effusion.

• Endocardium: – Mostly mitral and aortic valve.– Valves are edematous and thickened with foci of

fibrinoid necrosis. (Aschoff nodules uncommon).– Verrucous endocarditis (small vegetations along lines

of valve closure).

• Acute changes may resolve completely or progress to scarring and chronic valvular deformities.

Rheumatic Fever: Involvement of Other Organs

• Arthritis: large joints, self limited, no chronic deformities.

• Lung: uncommon, chronic interstitial inflammation and fibrinous pleuritis.

• Skin: skin nodules, erythema marginatum.

Chronic Rheumatic Heart Disease

• Irreversible deformity of one or more cardiac valves (previous acute valvulitis).

• Left side of heart > right.

• Reduction of diameter (stenosis), or improper closure (regurgitation), or both.

• May lead to cardiac failure (overload)

• May predispose to infective endocarditis.

Chronic Rheumatic mitral valvulitis• Stenosis > regurgitation.• Females > males.• In stenosis:

– Leaflets are thick, rigid, and interadherent.– Dilatation and hypertrophy of left atrium.– Mural thrombi may be present systemic emboli.– Lungs are firm and heavy (chronic passive congestion).– Right heart may be affected later.

• In regurgitation:– Retracted leaflets.– Left ventricular hypertrophy and dilatation.

Chronic Aortic Valvulitis

• Males > females.• Associated with mitral valvulitis.• Aortic stenosis:

– Valve cusps are thickened, firm and interadherent rigid triangular channel.

– Left ventricular hypertrophy.– Subsequent left ventricular failure and dilation.

• Aortic regurgitation: retraction of leaflets.

Acute Rheumatic Fever: Clinical• Occurs 10 days to 6 weeks after pharyngitis.• ? Of genetic susceptibility.• Peak incidence: 5-15 years.• Pharyngeal culture may be negative, but anti

streptolysin O (ASO) titer will be high.• Arthritis: large joints, migratory.• Acute carditis: pericardial friction rubs, weak heart

sounds, tachycardia and arrhythmias. myocarditis cardiac dilation functional mitral

valve insufficiency or even congestive heart failure.

Major criteria for diagnosis of rheumatic fever

• Migratory polyarthritis: a temporary migrating inflammation of the large joints, usually starting in the legs and migrating upwards.

• Carditis: inflammation of the heart muscle which can manifest as congestive heart failure with shortness of breath, pericarditis with a rub, or a new heart murmur.

Major criteria for diagnosis of rheumatic fever contd

• Subcutaneous nodules: painless, firm collections of collagen fibers over bones or tendons. They commonly appear on the back of the wrist, the outside elbow, and the front of the knees.

• Erythema marginatum: a long lasting rash that begins on the trunk or arms. This rash never starts on the face and it is made worse with heat.

Major criteria for diagnosis of rheumatic fever contd

• Sydenham's chorea (St. Vitus' dance): a characteristic series of rapid movements without purpose of the face and arms. This can occur very late in the disease.

Minor criteria for diagnosis of rheumatic fever

• Fever

• Arthralgia: Joint pain without swelling

• Raised Erythrocyte sedimentation rate or C reactive protein

• Leukocytosis

Minor criteria for diagnosis of rheumatic fever

• ECG showing features of heart block

• evidence of Streptococcal infection: elevated or rising Antistreptolysin O titre or DNAase.[1].

• Previous episode of rheumatic fever or inactive heart disease

Chronic Rheumatic Carditis: Clinical

• Manifestation after years or decades after the initial episode of rheumatic fever.

• Signs and symptoms depend on which involved valve(s): cardiac murmurs, hypertrophy, dilation, congestive heart failure, arrhythmia, thromboembolic complications and infective endocarditis.

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A. Acute rheumatic mitral valvulitis superimposed on chronic rheumatic heart disease. Small vegetations (verrucae) are visible along the line of closure of the mitral valve leaflet (arrowheads). Previous episodes of rheumatic valvulitis have caused fibrous thickening and fusion of the tendinous cords.

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B. Microscopic appearance of an Aschoff body in a patient with acute rheumatic carditis. The myocardial interstitium has a circumscribed collection of mononuclear inflammatory cells, including some large histiocytes with prominent nucleoli, a prominent binuclear histiocyte, and central necrosis.

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C. & D. Mitral stenosis with diffuse fibrous thickening and distortion of the valve leaflets, commissural fusion (arrow in C), and thickening and shortening of the tendinous cords. Marked dilation of the left atrium is noted in the left atrial view ( C).

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D. Opened valve. Note the neovascularization of the anterior mitral leaflet (arrow).

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E. Surgically removed specimen of rheumatic aortic stenosis demonstrating thickening and distortion of the cusps with commissural fusion ( E from Schoen FJ, St. John-Sutton M:

Contemporary issues in the pathology of valvular heart disease. Hum Pathol 18:568, 1967.)

Infective Endocarditis• Definition: infection of the cardiac valves

or mural surface of the endocardium, resulting in the formation of an adherent mass of thrombotic debris and organisms.

• Divided into:– Acute: high virulent organisms (staphylococcus

aureus), infect even normal valves, progress rapidly, little local host reaction.

– Subacute: infection of previously abnormal valves by organisms of low virulence (-hemolytic streptococci), progress slowly, induce local inflammatory reaction.

Infective Endocarditis: Etiology, Pathogenesis

• Bacteremia: i.v. drug abusers, elsewhere infection, previous dental, surgical or interventional procedure (catheterization).

• In some cases the source of bacteremia is occult.• Infective endocarditis is a particularly difficult

infection to eradicate because of the avascular nature of the heart valves.

Infective Endocarditis: Risk Factors

• Cardiac abnormalities: chronic valvular diseases, high pressure shunts within the heart (small ventricular septal defects).

• Prosthetic heart valves.

• Intravenous drug abusers.

Infective Endocarditis: Causative Organisms

• Most common of non prosthetic valves (50-60%):

-Hemolytic (viridans) streptococci, which attack previously damaged valves.

• Staphylococcus attack healthy or deformed valves (10-20%).

• Prosthetic valve endocarditis is caused commonly by coagulase-negative staphylococci (e.g., S. epidermidis).

Infective Endocarditis: Morphology

• Valvular vegetations containing bacteria or other organisms.

• Aortic and mitral valves are the most common sites. (right side valves in i.v.users)

• Vegetations may be single or multiple, involve one or more valve(s), differ in appearance according to the causative agent.

Infective Acute Endocarditis: Morphology

• Vegetations: may obstruct valve orifice, lead to rupture of ( the leaflets, cordae tendineae, or papillary muscles), abscess in perivalvular tissue (ring abscess), friable vegetations may become systemic emboli infarcts + abscesses.

• Micro: large number of organisms + fibrin and blood cells. Neutrophilic inflammatory reaction occurs the infection extends beyond the avascular valves.

Infective Subacute Endocarditis: Morphology

• Vegetations are firmer, less destructive, and ring abscess are uncommon.

• Micro: Granulation tissue is seen at the base of the vegetations, later: fibrosis, calcifications and chronic inflammatory infiltrates. Systemic emboli may develop but they don’t undergo suppuration.

Infective Endocarditis: Clinical• Onset: gradual or explosive (~organisms).

– Low-grade fever, malaise, weight loss.

– High fever, shaking chills.

• Cardiac murmurs.

• Enlargement of spleen, clubbing of digits (particularly in subacute cases).

• Systemic emboli (neurologic deficits, retinal abnormalities, necrosis of digits, and infarcts of the myocardium.

• Pulmonary emboli in right-sided endocarditis.

• Mycotic aneurysms.

• Petechiae (due to micro emboli or deposition of immune complexes.

• Renal lesions: renal infarcts and glomerulonephritis.

• Valvular regurgitation and congestive heart failure due to progressive valvular destruction.

• Blood culture for aerobic and anaerobic organisms is very important (only minority of cases remain negative).

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Endocarditis of the mitral valve (subacute, caused by Streptococcus viridens). The irregular, large friable vegetations are denoted by arrows.

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B. Acute endocarditis of a congenitally bicuspid aortic valve (caused by Staphylococcus aureus) with severe cuspal destruction and ring abscess (arrow).

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C. Histologic appearance of vegetation of endocarditis with extensive acute inflammatory cells and fibrin. Bacterial organisms were demonstrated by tissue Gram stain.

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D. Gross photograph illustrating healed endocarditis with perforations on bicuspid aortic valve

Nonbacterial Thrombotic EndocarditisNBTE (marantic endocarditis)

• Characterized by the deposition of small masses of fibrin, platelets, and other blood components on the leaflets of the cardiac valves (sterile).

• Pathogenesis/ association:– Subtle endothelial abnormalities.– Hypercoagulability.– Association with malignancy (50%).

Nonbacterial Thrombotic Endocarditis

• Gross:groups of small nodules on the lines of valve closure (similar to those of acute rheumatic fever), valve leaflets are normal.

• Aortic valve most common site.

• Micro: fibrin and platelets aggregates, no inflammation or fibrosis.

• Clinically asymptomatic, if large: may embolize, may become infected.

(Libman-Sacks) endocarditis

• Less commonly, noninfective, verrucous (Libman-Sacks) endocarditis attributable to elevated levels of circulating immune complexes may occur in patients with systemic lupus erythematosus

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Diagrammatic comparison of the lesions in the four major forms of vegetative endocarditis. The rheumatic fever phase of RHD (rheumatic heart disease) is marked by a row of warty, small vegetations along the lines of closure of the valve leaflets. IE (infective endocarditis) is characterized by large, irregular masses on the valve cusps that can extend onto the cords (see Fig. 13–18 A). NBTE (nonbacterial thrombotic endocarditis) typically exhibits small, bland vegetations, usually attached at the line of closure. One or many may be present (see Fig. 13–20). LSE (Libman-Sacks endocarditis) has small or medium-sized vegetations on either or both sides of the valve leaflets.

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Nonbacterial thrombotic endocarditis (NBTE).

A. Nearly complete row of thrombotic vegetations along the line of closure of the mitral valve leaflets.

B. Photomicrograph of NBTE showing bland thrombus, with virtually no inflammation in the valve cusp (c) or the thrombotic deposit. The thrombus is only loosely attached to the cusp (arrow).

Pericarditis

• Primary: mostly viral, sometimes by other microorganisms (pyogenic bacteria, mycobacteria and fungi.

• Secondary to: acute myocardial infarction, cardiac surgery, or radiation to the mediastinum.

• Associated systemic disorders, mostly with uremia.

• Less common 2ndry causes: rheumatic fever, SLE, and metastatic malignancies (bloody effusions).

Pericarditis

• Cause immediate hemodynamic complications, if significant effusion is present.

• Resolve without significant sequelae.

• Progress to chronic fibrosing process.

Acute Pericarditis: Morphology

• In uremia, and acute rheumatic fever: the exudate is fibrinous and impart a shaggy irregular pericardial surface (bread and butter pericarditis).

• Viral pericarditis fibrinous exudate.• Acute bacterial pericarditis fibrinopurulent pericarditis.• Tuberculosis caseous materials.• Pericardial metastases: irregular nodules.• Exudate usually resolve unless there is excessive

suppuration or caseation, where healing leads to chronic pericarditis.

Chronic Pericarditis: Morphology

• Ranges from delicates adhesions to dense fibrotic scars that obliterate the pericardial space.

• In extreme cases the heart can’t expand during diastole : constrictive pericarditis.

Pericarditis: Clinical

• Atypical chest pain (worse on reclining).

• High pitch friction rub.

• Significant exudate cardiac tamponade faint distant heart sounds, distended neck veins, declining cardiac output, and shock.

• Chronic constrictive pericarditis venous distension and low cardiac output.

Hemopericardium

• Accumulation of large amounts of blood in the pericardial space is called as hemopericardium.

• Hemopericardium can be seen in rupture of the myocardium secondary to acute myocardial infarction. It may also be seen in pericarditis especially when it is secondary to metastatic nodule in the pericardial space.

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Acute suppurative pericarditis as an extension from pneumonia. Extensive purulent exudate is evident in this in situ photograph.