Infective endocarditis By Dr. Ashraf Abdelfatah Deyab Assistant Professor of Pathology Majmaah University- Collage of Medicine

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

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”.

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)

(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.

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)

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.

(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)

(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)

(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

(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

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)

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

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. .

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.

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

Histologic appearance of vegetation abscess formation

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

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.

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

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 ) .

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

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)

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

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.

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

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

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).

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 ???