INFECTIVE ENDOCARDITIS HA MWKYOMA, MD

DEFINITION OF IE Is a microbial infection of the endocardial surface of the heart and has been classified as "acute" or "subacute –chronic" on the basis of severity of the clinical presentation and the progression of the untreated disease. The characteristic lesion, a vegetation, is composed of a collection of platelets, fibrin, microorganisms, and inflammatory cells

IE It most commonly involves heart valves but may also occur at the site of a septal defect, on the chordae tendineae, or on the mural endocardium.  Men are more often affected than women.

Infective Endocarditis Essential characteristics, General definitions and epidemiology NVE I.V. drug abuse PVE Pathogenesis Pathophysiology Clinical features Treatment

Epidemiology Underlying valvular abnormality predisposing to infective endocarditis rheumatic fever a common cause in the past mitral valve prolapse currently represents the most common underlying cardiac abnormality

Risk for Endocarditis High risk prosthetic cardiac valve prior episodes of endocarditis complex congenital cardiac defect surgically constructed systemic-pulmonary shunts or conduits

Risk for Endocarditis Moderate risk patent ductus arteriosus VSD, primum ASD coarctation of the aorta bicuspid aortic valve hypertrophic cardiomyopathy acquired valvular dysfunction MVP with mitral regurgitation

Risk for Endocarditis Low risk isolated secundum atrial septal defect ASD, VSD, or PDA >6 months past repair “innocent” heart murmur by auscultation in the pediatric population “innocent” heart murmur by echocardiography in adult patients

Infective Endocarditis General characteristics Febrile illness Persistent bacteremia Characteristic lesion of microbial infection of the endothelial surface of the heart ( the vegetation) Variable in size Amorphous mass of fibrin & platelets Abundant organisms Few inflammatory cells

Infective Endocarditis Typically involves the valves May involve all structures of the heart Chordae tendinae Sites of shunting Mural lesions Infection of vascular shunts, by strict definition, is endarteritis, but lesion is the same Majority of cases caused by Gram-positive bacteria namely; streptococcus, staphylococcus, enterococcus, or fastidious gram negative cocco-bacillary forms

Infective Endocarditis Gram negative organisms P. aeruginosa most common HACEK - slow growing, fastidious organisms that may need 3 weeks to grow out of culture Haemophilus sp. Actinobacillus Cardiobacterium Eikenella Kingella

Infective Endocarditis Acute Toxic presentation Progressive valve destruction & metastatic infection developing in days to weeks Most commonly caused by S. aureus Subacute Mild toxicity Presentation over weeks to months Rarely leads to metastatic infection Most commonly S. viridans or enterococcus

Infective Endocarditis Case rate may vary between 2-3 cases /100,000 to as high as 15-30/100,000 depending on incidence of i.v. drug abuse and age of the population 55-75% of patients with native valve endocarditis (NVE) have underlying valve abnormalities MVP Rheumatic Congenital i.v. drug abuse

Infective Endocarditis Pediatric population The vast majority (75-90%) of cases after the neonatal period are associated with an underlying congenital abnormality Aortic valve VSD Tetralogy of Fallot Risk of post-op infection in children with IE is 50% Microbiology Neonates: S. aureus, coag – staph, group B strep Older children: 40% strep, S. aureus

Infective Endocarditis Adult population MVP – prominent predisposing factor High prevalence in population 2-4% 20% in young women Relative risk in MVP ~3.5 – 8.2, largely confined to patients with murmur, but also increased in men and patients >45 years old

Infective Endocarditis Adult population Rheumatic Heart Disease 20 – 25% of cases of IE in 1970’s & 80’s 7 – 18% of cases in recent reported series Mitral site more common in women Aortic site more common in men Congenital Heart Disease 10 – 20% of cases in young adults 8% of cases in older adults PDA, VSD, bicuspid aortic valve (esp. in men>60)

Infective Endocarditis Intravenous Drug Abuse Increased frequency of gram negative infection such as P. aeruginosa & fungal infections High concordance of HIV positivity & IE (27-73%) HIV status does not in itself modify clinical picture Survival is decreased if CD4 count < 200/mm3

Infective Endocarditis Intravenous Drug Abuse Risk is 2 – 5% per pt./year Tendency to involve right-sided valves Distribution in clinical series 46 – 78% tricuspid 24 – 32% mitral 8 – 19% aortic Underlying valve normal in 75 – 93% S. aureus predominant organism (>50%, 60-70% of tricuspid cases)

Infective Endocarditis Prosthetic Valve Endocarditis (PVE) 10 – 30% of all cases in developed nations Early PVE – within 60 days Nosocomial (S. epid. predominates) Late PVE – after 60 days Community (same organisms as NVE)

Infective Endocarditis Pathology NVE infection is largely confined to leaflets PVE infection commonly extends beyond valve ring into annulus/periannular tissue Ring abscesses Septal abscesses Fistulae Prosthetic dehiscence Invasive infection more common in aortic position and if onset is early

Infective Endocarditis Nonbacterial Thrombotic Endocarditis (NBTE) Endothelial injury Hypercoagulable state Lesions seen at coaptation points of valves Atrial surface mitral/tricuspid Ventricular surface aortic/pulmonic Modes of endothelial injury High velocity jet Flow from high pressure to low pressure chamber Flow across narrow orifice of high velocity Bacteria deposited on edges of low pressure sink or site of jet impaction Platelet-fibrin thrombi

Infective Endocarditis Pathogenesis Endothelial damage Platelet-fibrin thrombi Microorganism adherence

Pathogenesis Disruption of the endocardial layer as a complication of abnormal blood flow associated with underlying cardiac defect Bacterium-endothelium interaction with bacterial attachment and invasion of endothelial cells

Pathophysiology Clinical manifestations Direct Indirect Constitutional symptoms of infection (cytokine) Indirect Local destructive effects of infection Embolization – septic or bland Hematogenous seeding of infection N.B. may present as local infection or persistent fever, metastatic abscesses may be small, miliary Immune response Immune complex or complement-mediated

Pathophysiology Local destructive effects Valvular distortion/destruction Chordal rupture Perforation/fistula formation Paravalvular abscess Conduction abnormalities Purulent pericarditis Functional valve obstruction

Pathophysiology Embolization Clinically evident 11 – 43% of patients Pathologically present 45 – 65% High risk for embolization Large > 10 mm vegetation Hypermobile vegetation Mitral vegetations (esp. anterior leaflet) Pulmonary (septic) – 65 – 75% of i.v. drug abusers with tricuspid IE

Coagulase-negative Staphylococci can produce native-valve endocarditis in mitral valve prolapse usually subacute, difficult to diagnose, and disregarded as a contaminant delay in diagnosis and treatment may account for the severe complications myocardial abscess formation valvular insufficiency requiring valve surgery death

Prosthetic Heart Valve positive blood culture in hospitalized patients with underlying prosthetic valves can be a harbinger of endocarditis 43% patients with nosocomial bacteremia or fungemia had prosthetic valve infection a serious complication

Clinical Features Interval between index bacteremia & onset of sx’s usually < 2 weeks May be substantially longer in early PVE Fever most common sign May be absent in elderly/debilitated pt. Murmur present in 80 – 85% Generally indication of underlying lesion Frequently absent in tricuspid IE Changing murmur

Classical Peripheral Manifestations Less common today Not seen in tricuspid endocarditis Petechiae most common

Janeway Lesions

Splinter Hemorrhage

Osler’s Nodes

Subconjunctival Hemorrhages

Roth’s Spots

Clinical Features Systemic emboli Neurological sequelae CHF Incidence decreases with effective anti-microbial Rx Neurological sequelae Embolic stroke 15 – 20% of patients Mycotic aneurysm Cerebritis CHF Due to mechanical disruption High mortality without surgical intervention Renal insufficiency Immune complex mediated Impaired hemodynamics/drug toxicity

Diagnosis Published criteria for diagnostic purposes in obscure cases High index of suspicion in patients with predisposing anatomy or behavior Blood cultures Echocardiography

Goals of Therapy Eradicate infection Definitively treat sequelae of destructive intra-cardiac and extra-cardiac lesions

Antibiotic Therapy Treatment tailored to etiologic agent Important to note relationship for each causative organism and the antibiotic used High serum concentration necessary to penetrate avascular vegetation

Antibiotic Therapy Treatment before blood cultures turn positive Suspected ABE Hemodynamic instability Neither appropriate nor necessary in patient with suspected SBE who is hemodynamically stable

Antibiotic Therapy Effective antimicrobial treatment should lead to defervescence within 7 – 10 days Persistent fever in: IE due to staph, pseudomonas, culture negative IE with microvascular complications/major emboli Intracardiac/extracardiac septic complications Drug reaction

Prevention Prophylactic regimen targeted against likely organism Strep. viridans – oral, respiratory, eosphogeal Enterococcus – genitourinary, gastrointestinal S. aureus – infected skin, mucosal surfaces

Prevention – the procedure Dental procedures known to produce bleeding Tonsillectomy Surgery involving GI, respiratory mucosa Esophageal dilation Gallbladder surgery Cystoscopy, urethral dilation Urethral catheter if infection present Urinary tract surgery, including prostate I&D of infected tissue

Prevention – the underlying lesion High risk lesions Prosthetic valves Prior IE Cyanotic congenital heart disease PDA AR, AS, MR,MS with MR VSD Coarctation Surgical systemic-pulmonary shunts Intermediate risk MVP with murmur Pure MS Tricuspid disease Pulmonary stenosis ASH Bicuspid Ao valve with no hemodynamic significance Lesions at highest risk

Summary You need to go to medical school (and graduate) in order to take care of patients with endocarditis.