Infective endocarditis

Definition – Infective endocarditis is a microbial infection of the heart valves or mural endocardium that leads to the formation of vegetations composed of thrombotic debris and organisms, often associated with destruction of the underlying cardiac tissue
Infective endocarditis is classified on clinical grounds into acute and subacute forms indicating the severity of disease which depends upon the virulence of infecting organism
Acute infective endocarditis-
- Infection of previously normal heart valve by highly virulent organism (staphylococcus aureus) that rapidly produces necrotizing and destructive lesions
- Death ensue with in days to weeks despite appropriate treatment with antibiotics and surgery
Sub acute infective endocarditis
- Infection by organisms of lower virulence (Streptococci viridans) that causes insidious infections of deformed valves with over all less destruction
- Disease has course of weeks to months and cure can be achieved with antibiotics

Etiopathogenesis

Organisms causing are
- 50% to 60% of cases affecting previously damaged or otherwise abnormal valves – Streptococcus viridans (normal component of oral cavity flora)
- 20% to 30% of cases affecting healthy or deformed valves – Staphylococus aureus
- IE in IV drug abusers – Staphylococcus aureus
- Prosthetic valve endocarditis is caused most commonly by – Coagulase negative staphylococci (Staphylococcus epidermidis)
- Other bacterial causes include Enterococci and HACEK group
  - H – Haemophilus
  - A- Actinobacillus
  - C – Cardiobacterium
  - E – Eikenella
  - K – Kingella
- Other agents causing endocarditis include – Gram negative bacilli and fungi
- In 10% of cases – no organism is identified (“Culture negative” endocarditis)
- Causes for the culture negative endocarditis are
  - Prior antibiotic therapy
  - Difficulty in isolating the offending agent
  - Organism is deeply embedded in enlarged vegetation that it cannot be released into blood
Predisposing factors
- 3 main types of predisposing factors leading to bacterial endocarditis are
  - Conditions that causes seeding of microorganisms into the blood (Bacteremia or Fungemia)
  - Underlying heart disease
  - Impaired host defenses
- Source of infection may be
  - Periodontal infections and dental procedures
  - Contaminated needle shared by IV drug abusers
  - Infections of genitourinary tract during procedures like catheterization, cystoscopy, and obstetrical procedures during normal delivery or abortions
  - Infections and surgeries of bowel and biliary tract
  - Skin infections like boils, carbuncles and abscesses
  - Respiratory tract infections
  - Cardiac catheterization and surgery for valve replacement
- Commonly associated underlying heart diseases are
  - Chronic rheumatic valvular disease (50% of cases)
  - Congenital heart diseases (20% of cases) like
    - VSD, PDA, Sub aortic stenosis, pulmonary stenosis, bicuspid aortic valve and coarctation of aorta

- - Other causes are
    - Syphilitic valvular disease, atherosclerotic valvular disease, floppy mitral valve, prosthetic heart valves
- Impaired host defenses
  - Impaired specific immunity in lymphomas
  - Leukemias
  - Cytotoxic therapy for cancer patients and transplant patients
  - Deficient functions of neutrophils and macrophages

Pathogenesis

Bacteria from blood stream in any of the above mentioned routes are implanted on the cardiac valves or mural endocardium as they have surface adhesion molecules which mediate their adherence to endocardium
Conditions predispose to implantation are –
- Previously damaged valves from diseases like RHD, congenital heart disease and prosthetic valves
- Hemodynamic stress
These conditions causes damage to endothelium on valves, favoring the formation of platelet-fibrin thrombi which get infected from circulating bacteria where they proliferate and form vegetations
Vegetations can embolize and as their embolic fragments contain virulent organisms, abscesses develop where they lodge, leading to sequelae such as septic infarcts or mycotic aneurysms
Vegetations of subacute endocarditis are associated with less valvular destruction than acute endocarditis

Morphology

Classic hall mark of Infective endocarditis is vegetations on heart valves
Common sites – valves of left heart (Valves of right heart are involved in intravenous drug abusers)
Most frequently on the mitral followed by aortic, simultaneous involvement of both mitral and aortic and rarely on the valves of right heart
In SABE, vegetations are found on diseased valves and in ABE, vegetations are found on previously normal valves
Location – on the atrial surface of atrioventricular valve and ventricular surface of semilunar valves
Vegetations can be single or multiple and may involve more than one valve
Occasionally they can erode into underlying myocardium and produce an abscess (ring abscess)

Gross
- Size – from few mm to several centimeters
- Appearance – Flat, filiform, fungating or polypoidal
- Grey-tawny to greenish, irregular, single or multiple and typically friable present along the closure of cusps
- Vegetations in ABE are bulkier and globular than those of SABE.
- Vegetations in ABE may cause ulceration or perforation of the underlying valve leaflet or may produce myocardial abscess
Microscopy
- Vegetations consists of 3 zones
  - Outer layer or cap – consists of eosinophilic material composed of fibrin and platelets
  - Underneath this layer is basophilic zone containing colonies of bacteria
  - Deeper zone – consists of non-specific inflammatory reaction. In SABE there may be granulation tissue (evidence of repair)
  - In Acute BE – inflammatory infiltrate consists mainly of neutrophils and is accompanied by tissue necrosis and abscess in the valve ring
  - In Subacute BE – healing by granulation tissue with mononuclear infiltrate and proliferating fibroblast are present

Complications of Infective endocarditis
- Complications begin in first few weeks of onset and are divided into cardiac and extra cardiac
- Cardiac complications
  - Valvular stenosis or insufficiency
  - Perforation, rupture and aneurysm of valve leaflets
  - Abscess in the valve ring
  - Myocardial abscesses
  - Suppurative pericarditis
  - Cardiac failure from one or more of the foregoing complications
- Extra cardiac complications
  - Extra cardiac manifestations are due to friable vagetations which get dislodged into the blood stream forming emboli
  - Emboli from left side of the heart – Enters the systemic circulation and affect organs like spleen, brain, kidneys producing infarcts, abscesses and mycotic aneurysms
  - Kidneys – petechial hemorrhages (Flea bitten). Focal glomerulonephritis and infarction may develop
  - Spleen – Splenic enlargement and infarction with pain
  - Brain – infarction with neurological dysfunction
  - Emboli from right side of the heart – enters the pulmonary circulation and produces pulmonary abscesses
  - Petechiae may be seen in skin and conjunctiva due to emboli or toxic damage to capillaries
  - In SABE, Oslers nodes, Roth spots and in ABE , Janeway lesions may appear due to toxic or allergic inflammation of the vessel wall
    - Oslers nodes – Painful small swelling (1cm) appearing at the tip of fingers or toes caused by deposition of immune complex and hypersensitivity vasculitis
    - Janeway lesions –
      - Small erythematous or hemorrhagic, macular non-tender lesions on palms and soles
      - These are microabscess of the dermis with marked necrosis and inflammatory infiltrate not involving the epidermis
      - They are caused by septic emboli which deposit bacteria, forming microabscesses
    - Roth spots –
      - Caused by immune complex mediated vasculitis
      - Retinal hemorrhages with pale center composed of coagulated fibrin
      - Flame shaped hemorrhages

- - Focal necrotizing glomerulonephritis due to circulating immune complexes

Reference

Vinay kumar, Abul K.Abbas, Nelson Fausto, Jon C. Aster. Robbins and Cotran Pathologic basis of disease. 8th edition

Infective endocarditis

Definition – Infective endocarditis is a microbial infection of the heart valves or mural endocardium that leads to the formation of vegetations composed of thrombotic debris and organisms, often associated with destruction of the underlying cardiac tissue

Infective endocarditis is classified on clinical grounds into acute and subacute forms indicating the severity of disease which depends upon the virulence of infecting organism

Acute infective endocarditis-

Infection of previously normal heart valve by highly virulent organism (staphylococcus aureus) that rapidly produces necrotizing and destructive lesions

Death ensue with in days to weeks despite appropriate treatment with antibiotics and surgery

Sub acute infective endocarditis

Infection by organisms of lower virulence (Streptococci viridans) that causes insidious infections of deformed valves with over all less destruction

Disease has course of weeks to months and cure can be achieved with antibiotics

Etiopathogenesis

Organisms causing are

50% to 60% of cases affecting previously damaged or otherwise abnormal valves – Streptococcus viridans (normal component of oral cavity flora)

20% to 30% of cases affecting healthy or deformed valves – Staphylococus aureus

IE in IV drug abusers – Staphylococcus aureus

Prosthetic valve endocarditis is caused most commonly by – Coagulase negative staphylococci (Staphylococcus epidermidis)

Other bacterial causes include Enterococci and HACEK group

H – Haemophilus

A- Actinobacillus

C – Cardiobacterium

E – Eikenella

K – Kingella

Other agents causing endocarditis include – Gram negative bacilli and fungi

In 10% of cases – no organism is identified (“Culture negative” endocarditis)

Causes for the culture negative endocarditis are

Prior antibiotic therapy

Difficulty in isolating the offending agent

Organism is deeply embedded in enlarged vegetation that it cannot be released into blood

Predisposing factors

3 main types of predisposing factors leading to bacterial endocarditis are

Conditions that causes seeding of microorganisms into the blood (Bacteremia or Fungemia)

Underlying heart disease

Impaired host defenses

Source of infection may be

Periodontal infections and dental procedures

Contaminated needle shared by IV drug abusers

Infections of genitourinary tract during procedures like catheterization, cystoscopy, and obstetrical procedures during normal delivery or abortions

Infections and surgeries of bowel and biliary tract

Skin infections like boils, carbuncles and abscesses

Respiratory tract infections

Cardiac catheterization and surgery for valve replacement

Commonly associated underlying heart diseases are

Chronic rheumatic valvular disease (50% of cases)

Congenital heart diseases (20% of cases) like

VSD, PDA, Sub aortic stenosis, pulmonary stenosis, bicuspid aortic valve and coarctation of aorta

Other causes are

Syphilitic valvular disease, atherosclerotic valvular disease, floppy mitral valve, prosthetic heart valves

Impaired host defenses

Impaired specific immunity in lymphomas

Leukemias

Cytotoxic therapy for cancer patients and transplant patients

Deficient functions of neutrophils and macrophages

Pathogenesis

Bacteria from blood stream in any of the above mentioned routes are implanted on the cardiac valves or mural endocardium as they have surface adhesion molecules which mediate their adherence to endocardium

Conditions predispose to implantation are –

Previously damaged valves from diseases like RHD, congenital heart disease and prosthetic valves

Hemodynamic stress

These conditions causes damage to endothelium on valves, favoring the formation of platelet-fibrin thrombi which get infected from circulating bacteria where they proliferate and form vegetations

Vegetations can embolize and as their embolic fragments contain virulent organisms, abscesses develop where they lodge, leading to sequelae such as septic infarcts or mycotic aneurysms

Vegetations of subacute endocarditis are associated with less valvular destruction than acute endocarditis

Morphology

Classic hall mark of Infective endocarditis is vegetations on heart valves

Common sites – valves of left heart (Valves of right heart are involved in intravenous drug abusers)

Most frequently on the mitral followed by aortic, simultaneous involvement of both mitral and aortic and rarely on the valves of right heart

In SABE, vegetations are found on diseased valves and in ABE, vegetations are found on previously normal valves

Location – on the atrial surface of atrioventricular valve and ventricular surface of semilunar valves

Vegetations can be single or multiple and may involve more than one valve

Occasionally they can erode into underlying myocardium and produce an abscess (ring abscess)

Gross

Size – from few mm to several centimeters

Appearance – Flat, filiform, fungating or polypoidal

Grey-tawny to greenish, irregular, single or multiple and typically friable present along the closure of cusps

Vegetations in ABE are bulkier and globular than those of SABE.

Vegetations in ABE may cause ulceration or perforation of the underlying valve leaflet or may produce myocardial abscess

Microscopy

Vegetations consists of 3 zones

Outer layer or cap – consists of eosinophilic material composed of fibrin and platelets

Underneath this layer is basophilic zone containing colonies of bacteria

Deeper zone – consists of non-specific inflammatory reaction. In SABE there may be granulation tissue (evidence of repair)

In Acute BE – inflammatory infiltrate consists mainly of neutrophils and is accompanied by tissue necrosis and abscess in the valve ring

In Subacute BE – healing by granulation tissue with mononuclear infiltrate and proliferating fibroblast are present