1. Infective endocarditisBy
Dr. Ashraf Abdelfatah Deyab
Assistant Professor of Pathology
Majmaah University- Collage of Medicine

2. Objectives
Definition & classification
Predisposing factors.
Common causes.
Pathogenesis
Morphological features
Clinical features

3. Endocarditis- definition
Endocarditis defined as:
inflammation of the inner layer of the heart, usually due to hematogenously transmitted infections .
Infective endocarditis:
Inflammation of endocardium with cardiac valves, with formation of adherent colonization or invasive mass made up of thrombotic debris and organisms, termed a “vegetation”.

4. Endocarditis classification
There are multiple ways to classify endocarditis, Simple way of classification :
1) Infective endocarditis.
a) Bacterial infection (Bacterial endocarditis)
the commonest causes are bacteria.
b) Fungal infection (ICU patients, IVDU
2) Non-infective endocarditis. (sterile)

5. (IE) clinical classification
Clinical classification: depend on aggressiveness of the causative agents
Acute infective endocarditis
necrotizing, ulcerative, destructive lesions.
Sub-acute infective endocarditis
the organisms are of lower virulence, e.g. Str.viridans subtype, HACEK, S. aureus (coagulase -ve), fungal, forming insidious infections of deformed valves that are less destructive.

6. Infective endocarditis (IE) how common??
IE is 3 times as common in males as in females. It has no racial predilection.
IE was approximately 12.7 cases per 100,000 persons per year (USA, 2009)

7. IE-predisposing factors
Cardiac Valvular abnormalities.
* preexisting cardiac abnormalities – RHD, MVP.
* prosthetic heart valves OR > surgery.
* Congenital HD or repaired
Dental & Surgical procedures.
Contaminated needle shared by IV drug
Breaks in the epithelial barriers of the gut, oral cavity, or skin.
Immuno-compromised patients
around 30% occur on normal valves.

8. (IE) Pathogenesis Step 0– Significant bacteremia.
Step 1:Endocardial damage due to any physical means + turbulence flow e.g. CHD+ prosthetic valves, IV drug abuser, catheter etc
Step II: Physical injury\lesion of valve or endocardium – result in exposure to the underlying ECM proteins& production of tissue factor- initiate Healing process: (deposition of Fibrin and Platelets)

9. (IE) Pathogenesis
. Step III: Colonization of damaged valve by bacteria circulating in the blood- ideal environment for bacteria adherence and invasion.
Certain bacteria equipped with several surface adhesions to ECM esp.(strep. Spp, staph aureus, enterococci) and molecule help in invasion (fibronectin-binding)

10. (IE) Pathogenesis Injury to the endocardium or valves depend on:
1) Dose of circulating bacteria.
2) Types of bacteria.
3) Duration of exposure, e.g transient bacteremia (tooth brushing, chewing, dental procedures). 4) Role of Host defenses.
Sub-acute IE has additional immunological phenomena

11. (Sub-acute IE) Pathogenesis
Sub-acute IE has additional immunological phenomena .
Markedly Increased levels of agglutinating and complement-fixing bactericidal antibodies and cryoglobulins.
The extracardiac manifestations-due to circulating immune-complexes (eg, Osler nodes, Roth spots, subungual hemorrhages), and, possibly, musculoskeletal abnormalities

12. COMMONEST CAUSATIVE AGENTS
Commonest organisms are gram positive
1) Virulent S. aureus
found on the skin can infect either health or deformed valves. (Acute IE)
Coagulase-neg.staphylococci (S. epidermidis)- Prosthetic valves (Subacute ) _____________________________________ 2) Streptococcus : Streptococcus viridans
(oral cavity- normal flora) : can infect either healthy or deformed valves. (Sub-acute IE)
Group A, C, and G streptococci (Acute IE)

13. COMMONEST CAUSATIVE AGENTS
3) HACEK group :
(Haemophilus, Actinobacillus, Cardiobacterium , Eikenella, and Kingella), all commensals in the oral cavity.
4) Enterococci, aerobic and anaerobic gram-negative rods.
5) Others

14. IE Morphological changes common site
Aortic valve – left heart
Mitral valve – left heart
Right heart – involved mainly in drugs abuser.
Single or multiple lesion > one valve.
Hall marks-morphology: is characterized by a prototypic lesion, the vegetation. .

15. IE morphology (Acute)
Vegetations: presence of friable, bulky, potentially destructive ( made up of fibrin, inflammatory cells, and bacteria or other organisms) on heart valves.
Ring abscess: erosion into the underlying myocardium and produce an abscess.
Emboli – shed from vegetations; leading to sequelae such as septic infarcts or mycotic aneurysms.

18. Acute endocarditis of congenital bicuspid aortic valve Extensive cuspal destruction and ring abscess

19. Histologic appearance of vegetation abscess formation

20. Histologic appearance of vegetation abscess formation demonstrates friable vegetations of fibrin and platelets (pink) , inflammatory cells and bacterial colonies

21. IE – morphology (sub-acute)
Sub-acute endocarditis:
- Less valvular destruction.
- Vegetations with granulation tissue,
indicative of healing process in the base.
- fibrosis, calcification, and a chronic
inflammatory infiltrate can develop.

22. IE – clinical features Heart Murmur- > 85% of cases. Peteachaie,
Acute Symptoms:
Explosive rapidly developing fever, or of low grade+ chills, weakness.
Signs:
Heart Murmur- > 85% of cases.
Peteachaie,
Small splinter hemorrhages of Fingers (sub-ungual),
Osler node in distal part of the digits
Roth spots: Retinal hemorrhages; rare

23. IE – clinical features Systemic embolization- effects
Signs of neurologic disease, 40% of patients, include : Embolic stroke with focal neurologic deficits, Intracerebral hemorrhage, multiple micro-abscesses
Others:
Mycotic aneurysm (weak BV, hemorrhage)
2) Renal Lesions, Infarcts, GN (trapping of immune complexes ) .

24. Sub-ungual “finger” - small splinter hemorrhages in a patient with infective endocarditis

25. Diagnostic Criteria for Infective Endocarditis
- Pathological criteria:
- Histologic findings (+ve vegetation or abscess).
- Two or more Positive blood culture for same organism.
- Embolus
II) - Clinical criteria:
(a) Major - Blood culture(s) positive “multiple”.
Echocardiographic identification
New valvular regurgitation.
(b) Minor- fever, not diagnostic Echo, vascular abnormality
Other not-significant bacteria, vascular lesion
Immunological phenomena e.g GN , osler nodes, cerebral hemorrhage
Duke Diagnostic criteria: (physical, lab, echo, blood culture)

26. Diagnostic Criteria for Infective Endocarditis
A definitive clinical diagnosis can be made based on the following:
2 major criteria
1 major criterion and 3 minor criteria
5 minor criteria

27. NON-INFECTED (Sterile) VEGETATIONS
Caused by:
Nonbacterial thrombotic endocarditis:
- Non-invasive vegetation (small sterile thrombi).
- No inflammation detected.
- Single or multiple along the line of closure of the leaflets or cusps.
2) The endocarditis of (SLE), called Libman-Sacks endocarditis.

28. Nonbacterial thrombotic endocarditis (NBTE)
Nonbacterial thrombotic endocarditis (NBTE). Thrombotic vegetations along the line of closure of the mitral valve

29. Nonbacterial thrombotic endocarditis (NBTE Bland thrombus, no inflammation in the valve cusp

30. IE Complications
Heart failure, due to Myocarditis & valvular defect > 90%
Metastatic infection & Immunological phenomena (Sub-acute IE)
Renal: InfarctionGlomerulonephritis, & Hematuria.
Brain: hemorrhages, Infarction& retinal emboli.
Splenomegaly & infarct +\-.
Bleeding tendency (petechaie, splinter).

31. IE management
Antibiotic remain the mainstay for treating IE according to Blood culture results.
Surgery – play great role
Prognosis: Vegetations Very dangerous and virulence , difficult to cure, required surgery.
Death – days to weeks if not treated.
Prophylaxis ???