Infective Endocarditis

Airley E. Fish, MD

Echo Conference

January 16, 2008

Outline

• Definition• Epidemiology/Predisposing factors• Microbiology• Clinical manifestations• Cardiac complications• Diagnosis• Indications for TTE vs TEE• Treatment• Indications for surgery• Prognosis – mortality & relapse rates• Indications for antibiotic prophylaxis

Definition• Microbial infection of

endocardium• Vegetation

– Platelets– Fibrin– Microorganisms– Inflammatory cells

Images from www.escuela.med.puc.cl

Vegetation – Gross & Microscopic

Large, friable vegetation on the mitral valve

Low power view of endocardium & myocardium, showing a fibrin vegetation on the endocardial surface. Endocardium appears edematous & inflamed

Images from www.pathology.vcu.edu

Definition

• Location– Predominantly heart

valves, but can occur on/in:• Septal defects

• Chordae tendinae

• Mural endocardium

• Acute vs sub-acute/chronic– Temporal – Severity of clinical

presentation– Progression of untreated

disease

Conditions Predisposing to IE

• Factors altering immunity:– Immunosuppression– Diabetes– Chronic alcoholism

• Structural cardiac abnormalities:– AS, AR– Bicuspid aortic valve– MS, MR– Senile mitral ring calcification

• Factors causing bacteremia:– Dental work/Poor dental hygiene– IVDU– GU/GI procedures

• External factors:– Mechanical valves– Indwelling vascular catheters– Pacing wires (IV)

Modified from David M. Leder Echo Conference 01/07

Epidemiology/Predisposing Factors

• IE of native valves

• IE of prosthetic valves

• Nosocomial IE

Epidemiology/Predisposing Factors – Native Valves

• Incidence: 1.7-6.2 cases/100K person-years

• Gender: ♂ predominance (1.7:1)

• Age: > ½ of all cases occur in adults > 60– ↓ in incidence of RHD in post antibiotic era– ↑ in elderly

• ↑ degenerative valve disease • ↑ prosthetic valves• ↑ ‘ed exposure to nosocomial bacteremia

• History of infective endocarditis– Recurrence in 4.5% of large cohort of non-addicts

Epidemiology/Predisposing Factors – Native Valves

• Structural heart disease– ¾ of patients have preexisting structural

cardiac abnormality– MVP most common– MVP + MR + thickened leaflets = 5-8 x

risk IE!

• Injection-drug use – Trend toward younger patients – Incidence of 150-2000 per 100,000

person years (higher if co-existent valvular disease)

– Most significant risk factor for R-sided endocarditis

• L-sided disease more common in addicts• S. aureus predominant organism• Vegetations often larger (i.e. > 1 cm)

– Injection cocaine > other drugs

Epidemiology/Predisposing Factors – Native Valves

• HIV infection– S. aureus most frequent pathogen– Unusual organisms (e.g.

salmonella and listeria)– ?Independent risk factor for IE in

IVDA (unconfirmed)

• Other– Pregnancy– AV fistulas for HD– Central venous and PA catheters– Peritoneovenous shunts for

intractable ascites– Ventriculoatrial shunts for

hydrocephalus

Epidemiology/Predisposing Factors – Prosthetic Valves

• Prosthetic heart valves– 7-25% of cases (likely to

↑ with aging population)– 1-4% of valve recipients

during the 1st year after replacement

– 1% per year thereafter– Risk IE mechanical >

bioprosthetic 1st 3 months– Equivalent risk @ 5 years

Epidemiology/Predisposing Factors – Nosocomial IE

• Nosocomial endocarditis– 7-29% of all 3° care hospital cases– Dx >72 hours after admission with no evidence

of IE on admission or within 60 days of a prior admission if risk factor for bacteremia or IE during hospitalization

– Complication of bacteremia 2°• Invasive intravascular procedure• IV catheter-related infection

Microbiology• S. aureus (32%)• Viridans group streptococci (18%)• Enterococci (11%)

– Frequently implicated in nosocomial bacteremia, but endocarditis rare

• Coagulase-negative staphylococci (11%)– Most common pathogen in early prosthetic

valve IE

• Culture negative endocarditis (8%)• Streptococcus bovis (7%)

– Common in elderly– Preexisting colonic lesions

• Other streptococci (5%)• Other organisms (3%)

Microbiology• Fungi (2%)• HACEK - fastidious gram negative bacteria (2%)

– Haemophilus aphrophilus– Actinobacillus actinomycetemcomitans– Cardiobacterium hominis– Eikenella corrodens– Kingella kingae

• Non-HACEK gram-negative bacteria (2%)• Polymicrobial (1%)

– More common in association with IVDU

Clinical Symptoms

• Fever (80%)

• Anorexia (75%)

• Chills (40%)

• Dyspnea (40%)

• Weight loss (25%)

• Night sweats (25%)

• Myalgias/arthralgias (15%)

Adapted from Mandell et al 2000 (Karmpaliotis) and Leder Echo Conference 2007

Clinical Signs• Fever 90%

• Heart murmur 85%– Changing murmur (5-10%)– New murmur (3-5%)

• Peripheral manifestations 50%– Petechiae (20-40%)– Splinter hemorrhages (15%)– Osler nodes (10-20%)– Janeway lesions (< 10%)

• Splenomegaly 20-50%

• Septic complications 20%

• Clubbing 10-50%Adapted from Mandell et al 2000 (Karmpaliotis) and Leder Echo Conference 2007

Common Peripheral Manifestations of IE• Splinter hemorrhages

– Under fingernails– Usually linear & red

• Conjunctival petechiae

• Osler’s nodes (ouch!)– Tender SQ nodules– Pulp of digits/thenar eminence

• Janeway lesions– Nontender, erythematous,

hemorrhagic, or pustular, often on the palms/soles .

Reference:Firsche,C. and others,Mitral-Valve Endocarditis,N Engl J Med.Vol. 345,NO.10,September6,2001,P739.

Cardiac Complications

• CHF– 2° infection-induced valvular damage (AoV > MV)

• MI– 2° embolism of vegetation fragments → CHF

• Pericarditis – 2° coronary artery embolization → MI → pericarditis

• Extension beyond valve annulus– ↑ CHF, need for cardiac surgery, death

• Extension into septum– AV, fascicular, or BBB

• Erosion of mycotic aneurysm of sinus of Valsalva– Pericarditis, hemopericardium/tamponade, fistulas to R or L ventricle

Diagnosis• Clinical• Laboratory

– (+) blood cultures– Non-specific findings

• Anemia• Leukocytosis• Abnormal UA• ↑’ed ESR & CRP

• Electrocardiographic– New AV block

• Moderately high PPV for formation of myocardial abscess, but sensitivity low

– New fascicular block– New BBB

• Suggestive of perivalvular invasion, particularly if AV IE

• Echocardiographic

Diagnosis

• Duke criteria (clinical + laboratory + ECHO)– High specificity 99%– NPV > 92%

• Retrospective study 410 patients with IE– 72-90% agreement with ID expert assessment

• Most discrepencies 2º overly broad categorization of “possible” IE (experts rejected)

• Gave rise to “Modified Duke Criteria”

Modified Duke Criteria

• Definite– 2 major– 1 major + 3 minor– 5 minor

• Possible– 1 major + 1 minor– 3 minor

Modified Duke Criteria

• Major– Evidence of endocardial involvement with new

regurgitant murmur– Persistently (+) blood cultures– ECHO

• Discrete, echogenic, oscillating intracardiac mass located at site of endocardial injury

• Periannular abscess• New dehiscence of a prosthetic valve

Modified Duke Criteria• Minor

– Predisposition to IE (certain cardiac conditions/IVDU)• High risk

– Prior IE– AoV– RHD – Prosthetic valve– Coarctation– Complex cyanotic congenital heart disease

• Moderate risk– MVP with MR +/- thickened leaflets– Isolated MS– Tricuspid valve disease– PS– HCM

• Low or no-risk– Secundum ASD– Ischemic heart disease– CABG– MVP without MR and thickened leaflets

Modified Duke Criteria

• Minor– Fever > 38° C– Vascular phenomenon

• Aside from petechiae & splinter hemorrhages

– Immunologic phenomena• RF• GN• Osler’s nodes• Roth spots

– Microbiologic findings • (+) blood cultures that do not meet the major criteria

Diagnosis - Echocardiography• Transthoracic – rapid, non-

invasive– ↑ Specificity 98%– Sensitivity 60-70%

• Challenging 2° obesity, COPD, chest wall deformities

• Transesophageal – more costly, invasive– Sensitivity 75-95%– Specificity 85-98%– NPV > 92%– Particularly useful if:

• Prosthetic valves• Evaluation of myocardial

invasion

Echocardiography - Indications

• Pre-test probability of IE < 4%– TTE both cost effective & satisfactory for r/o IE

• Probability of IE 4-60%– TEE initially more cost effective, diagnostically

efficient• Unexplained bacteremia with GPC’s• Catheter-associated S. aureus bacteremia• Fever or persistent bacteremia with IVDU

TEE > TTE

• Signs of perivalvular extension/presence of myocardial abscess– Fever or persistent bacteremia– Heart block– CHF– New pathologic murmur in patient with IE

• Spectral & color-flow Doppler on TEE demonstrate flow– Fistulas– Pseudoaneurysms– Unruptured abscess cavities– Valve perforations

TEE > TTEAoV Regurgitation with Vegetation &

Valvular Destruction

AoV Vegetation on TTE PLA

AoV Vegetation TEE

Echodense mass attached to the noncoronary cusp of the AoV c/w a vegetation using TEE

Mitral Valve Vegetation with Abscess

FIGURE 1. Mitral valve vegetation shown on transesophageal echocardiography. The echodense area at the annulus (arrow) is characteristic of underlying abscess.

Multiple Vegetations AoV and MV

TTE PLA during diastole. Multiple vegetations on the anterior leaflet of the patient's mitral valve (arrows 1 and 2) and a 16 × 6 mm mobile vegetation on the aortic noncoronary cusp (arrow 3)

M Mode TTE MV with Multiple Echoes from Vegetations

M-mode echocardiogram demonstrating multiple echoes from vegetations on the anterior leaflet of the MV during diastole. Specific sign of cusp vegetations in IE.

Aspergillus Prosthetic Valve Endocarditis Causing Functional AS

Transesophageal echocardiography (TEE) was performed and revealed a 4 x 2 cm mass on the bioprosthetic AoV, encasing all three leaflets and severely limiting leaflet excursion (Figure 2). Doppler examination revealed a peak gradient of nearly 100 mmHg.

Treatment

• IV antimicrobial therapy for 4-6 weeks– Dependent upon

pathogen– Native vs prosthetic valve

• PCN G +/- gentamicin• Nafcillin/oxacillin +/-

gentamicin• Vancomycin +/- gentamicin• Ceftriaxone

Treatment

• Anticoagulation– Has not been shown to

prevent embolization– May ↑ risk of intracerebral

hemorrhage• S. aureus prosthetic valve IE

particularly susceptible

– Role of aspirin still under investigation

Surgical Therapy for Native Valve IE: Class I Indication (All < LOE B)

• Valvular stenosis or regurgitation → CHF– Strongest indication– Mortality in med rx 56-86% vs 11-35% med rx/surgery

• Hemodynamics @ time of surgery principle determinant of operative mortality

• AR or MR with hemodynamic e/o:– ↑’ed LVEDP – ↑’ed LA pressures– Moderate to severe pulmonary artery systolic HTN

• IE 2° fungal or other highly resistant organisms – Pseudomonas, brucella, coxiella, candida, ?enterococci (no synergistic Rx)

• lE complicated by:– Heart block– Annular or aortic abscess– Destructive penetrating lesions

• Sinus of Valsalva to RA, RV, LA fistula• Mitral leaflet perforation with AoV endocarditis• Infection in annulus fibrosa

Surgical Therapy for Native Valve IE: Other Indications (Both LOE C)

• Class IIa– Recurrent emboli & vegetations despite ABX

• Class IIb– Mobile vegetations > 10 mm with or without emboli

Surgical Therapy for Prosthetic Valve IE: Class I Indication (All LOE < B)

• Consultation with a cardiac surgeon

• Heart failure

• Dehiscence via cine-fluoroscopy or ECHO

• ↑ obstruction or regurgitation

• Complications (e.g. abscess formation)

Surgical Therapy for Prosthetic Valve IE: Other Indications (All LOE C)

• Class IIa– Persistent bacteremia/recurrent emboli despite ABX

• If cerebral infarcts, risk of worsening neurological deficits dependent upon time from initial embolus until surgery

• < 7 days, 8-14 days, > 4 weeks (44%, 16.7%, 2.3%)

– Relapsing infection

• Class III– Not indicated if uncomplicated IE 2° 1st time

infection with a sensitive organism

Mortality Rates

• Vary according to:– Causative microorganism

• > 50 % pseudomonas• 25-47% S. aureus • 15-25% enterococci• 5-37% Q-fever• 4-16% Strep viridans

– Presence of complications or coexisting conditions• CHF, neuro events, renal failure, severe immunosuppression 2° HIV

– Development of perivalvular extension/myocardial abscess– Use of combined medical and surgical Rx in appropriate

patients– Death 2° CNS embolic events/hemodynamic deterioration

• Native-valve/prosthetic valve as high as 20-25%• R-sided IE in IVDU approximately 10%

Relapse Rates

• Usually occurs within 2 months of DC’ing ABX• Native valve

– PCN-sensitive strep viridans < 2%– Enterococcus 8-20%– S. aureus, enterobacter, fungi

• Rx failure during 1° course of ABX

• Prosthetic valve– 10-15%– (+) blood culture at time of valve replacement RF for relapse,

particularly if staphylococcus endocarditis

Procedures That May Result in Transient Bacteremia

• Dental– Manipulation of gingival tissue or periapical region of teeth

• Respiratory tract– Incision or biopsy of respiratory tract mucosa (e.g.

tonisillectomy, bronchoscopy with biopsy)• GI/GU tract

– No longer considered high risk – no prophylaxis, unless active GI/GU infection

• Skin/Musculoskeletal tissue– If polymicrobial infection undergoing a surgical procedure

• Pregnancy– Only in highest risk cardiac conditions undergoing vaginal

delivery

Indications for Antibiotic Prophylaxis

• Prior history of IE• Prosthetic heart valves (including bioprosthetic &

homograft)• Unrepaired cyanotic congenital heart disease

– Including palliative shunts and conduits

• Completely repaired congenital heart defects with prosthetic material or device, whether placed by surgery or by catheter intervention during the 1st 6 months after the procedure

• Repaired congenital heart disease with residual defects at or adjacent to the site of the prosthetic device

• Cardiac valvulopathy in a transplanted heart

Antibiotic Prophylaxis No Longer Needed

• Bicuspid AoV

• Acquired aortic or mitral valve disease including:– MVP with regurgitation– Prior valve repair

• HCM with latent or resting obstruction