Infective Endocarditis (IE)

Definition

• Robbins & Kumar Basic Pathology, p. 368
• Goldman-Cecil Medicine, p. 700

Classification

Epidemiology

• Incidence in Western countries: approximately 3-14 cases per 100,000 persons/year
• The US sees roughly 10,000-20,000 new cases per year
• Shifting epidemiology: in developed countries, S. aureus (driven by healthcare exposure and IV drug use) has surpassed viridans streptococci as the most common causative agent
• In developing countries, rheumatic heart disease still predominates, with subacute disease caused by VGS in younger adults
• The opioid epidemic has contributed to rising IE rates, especially in rural US settings
• Braunwald's Heart Disease, p. 838

Predisposing Conditions / Risk Factors

• Mitral valve prolapse (especially with regurgitation) - the leading structural risk factor in developed countries
• Degenerative valvular disease
• Injection drug use (IV drug use - favors tricuspid involvement)
• Congenital heart disease (VSD, unrepaired cyanotic CHD)
• Previous IE
• Prosthetic heart valves (10-20% of all IE cases)
• Pacemaker/CIED lines and indwelling vascular catheters

• Rheumatic heart disease (still important in developing countries)
• Bicuspid aortic valve
• Hypertrophic obstructive cardiomyopathy
• Hemodialysis access

• Robbins & Kumar, p. 368; Goldman-Cecil Medicine, p. 700

Pathogenesis

1. Endothelial damage (from turbulent flow, jets, indwelling hardware) creates sterile platelet-fibrin deposits (non-bacterial thrombotic endocarditis - NBTE)
2. Transient bacteremia seeds these deposits
3. Organisms adhere, proliferate, and become embedded in a protective fibrin-platelet matrix forming vegetations
4. Portal of entry: dental/surgical procedures, IV drug injection, gut/oral flora, infected catheters, trivial skin injuries

• Staphylococci, streptococci, enterococci are the three most common worldwide
• S. viridans: 50-60% of community-acquired IE; damaged valves; subacute course
• S. aureus: most common in healthcare settings and IVDU; can infect normal valves; acute course
• HACEK group: Haemophilus, Aggregatibacter (Actinobacillus), Cardiobacterium, Eikenella, Kingella - oral commensals, slow-growing gram-negative bacilli
• Enterococci: genitourinary/GI portal of entry
• Culture-negative endocarditis (~10%): prior antibiotics, fastidious organisms (Coxiella burnetii/Q fever, Bartonella, Brucella, HACEK)

Morphology (Pathology)

(Robbins & Kumar - Comparison of vegetation morphology: RHD = small beaded vegetations along leaflet margins; IE = large, irregular, destructive vegetations; NBTE = small, sterile, non-destructive; LSE = Libman-Sacks in SLE)

• Sites: Aortic and mitral valves most common (left-sided); tricuspid valve in IVDU (right-sided)
• Vegetations may be single or multiple, on one or more valves
• Can erode into myocardium producing ring abscesses (especially aortic valve IE - can disrupt the conduction system causing heart block)
• Friable nature leads to septic emboli → abscesses, septic infarcts, mycotic aneurysms at embolic sites

Clinical Features

Symptoms

• Fever (most consistent sign - >90% of patients)
• Chills, night sweats, malaise, fatigue, weight loss, myalgias, arthralgias
• Subacute: vague flu-like illness; splenomegaly common
• Acute: rapidly developing fever, rigors, sepsis

Signs - "FROM JANE" (mnemonic)

Diagnosis: Modified Duke Criteria

• Pathologic criteria (culture/histology from vegetation or abscess), OR
• Clinical criteria: 2 major, OR 1 major + 3 minor, OR 5 minor criteria

Major Criteria

1. Blood culture positive for IE
   • Typical organisms (S. viridans, S. gallolyticus, S. aureus, HACEK, community-acquired enterococci) from ≥2 separate cultures
   • Persistently positive cultures (≥2 from samples >12 hr apart, or ≥3 of ≥4 samples)
   • Single positive culture for Coxiella burnetii OR anti-phase I IgG titer ≥1:800
2. Evidence of endocardial involvement (Echo/imaging)
   • Oscillating intracardiac mass on valve or supporting structures
   • Abscess / ring abscess
   • New partial dehiscence of prosthetic valve
   • New valvular regurgitation (worsening of pre-existing murmur NOT sufficient)
   • 18F-FDG PET/CT: abnormal metabolic activity at valve/prosthetic material (≥3 months after implantation) - added in 2023 updated criteria

Minor Criteria

1. Predisposing heart condition or IV drug use
2. Fever >38°C
3. Vascular phenomena: major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, Janeway lesions
4. Immunologic phenomena: glomerulonephritis, Osler nodes, Roth spots, rheumatoid factor
5. Microbiologic evidence: positive blood culture not meeting major criteria (excludes single coagulase-negative staphylococci)

• Braunwald's Heart Disease; Clinical Echocardiography (2023 Duke Criteria)

Investigations

• TTE is of poor quality or negative despite high clinical suspicion
• Prosthetic valve is involved
• S. aureus bacteremia
• Complications (paravalvular abscess) suspected

Complications

Management

Principles

• Every patient with IE should be managed inpatient at a center with an experienced multidisciplinary "IE team" (infectious disease, cardiology, cardiac surgery)
• Blood cultures must be drawn before antibiotics
• Prolonged parenteral antibiotics are the cornerstone
• Surgical consultation in all complicated cases

Antibiotic Therapy (General Principles)

Indications for Surgery

1. Heart failure or cardiogenic shock due to valvular dysfunction - most common surgical indication (Class I)
2. Locally uncontrolled infection - paravalvular abscess, fistula, enlarging vegetation despite appropriate antibiotics, persistent bacteremia
3. Prevention of embolism - large vegetation (>10 mm) especially with prior embolic event, or very large (>15 mm) vegetation
4. Prosthetic valve endocarditis - especially early PVE (<1 year after implantation), PVE with dehiscence, or S. aureus PVE
5. Fungal IE - almost always requires surgery

Antibiotic Prophylaxis (2021 AHA Update)

• Indications (AP suggested):
  • Prosthetic cardiac valve or prosthetic material used for valve repair
  • Transcatheter-implanted prosthetic valves
  • Previous IE
  • Unrepaired cyanotic CHD (including palliative shunts/conduits)
  • Repaired CHD with prosthetic material within the first 6 months post-procedure, or with residual defect
  • Cardiac transplant recipients with valvulopathy
  • New: Ventricular assist devices and implantable hearts
  • New: Melody valve and Contegra conduit
• Prophylaxis NOT suggested: Pacemakers/ICDs, septal defect closure (with complete closure), coronary stents, peripheral vascular grafts, vena cava filters
• Preferred agent: Amoxicillin 2 g PO 30-60 min before dental procedure (90% of "penicillin-allergic" patients will have negative skin testing and can use amoxicillin)
• Clindamycin removed as an alternative (risk of C. difficile)
• Doxycycline added as an alternative for truly penicillin-allergic patients

Prognosis

• Left untreated, IE is universally fatal
• With appropriate therapy, overall in-hospital mortality: 15-25%
• Worse prognosis: S. aureus, prosthetic valve IE, aortic IE, perivalvular extension, heart failure, large vegetations, elderly, immunocompromised
• Better prognosis: streptococcal IE, early surgery when indicated

Special Populations

• Tricuspid valve most common
• S. aureus predominates
• Septic pulmonary emboli (presenting as multiple nodular opacities/cavities on CXR/CT)
• Better prognosis than left-sided IE; some cases can be treated with shorter (2-4 week) antibiotic courses

• Early PVE (<60 days post-op): coagulase-negative staphylococci, S. aureus, gram-negatives, fungi
• Late PVE (>12 months): similar to native valve IE
• Higher morbidity/mortality; surgery often required
• TEE and PET/CT are especially valuable

• Braunwald's Heart Disease, 12th Ed. - Chapters 80, 80G
• Robbins & Kumar Basic Pathology - Chapter 9, p. 368
• Goldman-Cecil Medicine - Chapter 61, p. 700
• Textbook of Clinical Echocardiography (2023 Duke Criteria), Chapter 14
• Tintinalli's Emergency Medicine, Chapter 129