Endocarditis

Overview

Definition

• Infective endocarditis (IE) is caused by infection or inflammation of the inner lining of the heart (endocardium), most commonly affecting the heart valves.
• Noninfective endocarditis (NIE) results from the formation of sterile platelet and fibrin thrombi on cardiac valves and endocardium.

Epidemiology

Infective endocarditis:

• Most common form of endocarditis
• Incidence: 11–15 cases per 100,000 persons per year
• Mean age: 60.8 years (> 50% are > 50 years of age)
• 3 times more common in men

Noninfective endocarditis:

• Rare
• Often found on autopsy
• Incidence: 0.9%–1.6%
• Common age group: 30–70 years
• No sex predilection

Infective endocarditis etiologies

Infective endocarditis may be caused by numerous organisms; the list below is not exhaustive.

• Staphylococci:
  • Staphylococcus aureus (most common)
  • S. epidermidis
• Streptococci:
  • Streptococcus viridans (commonly after dental procedures)
  • S. pneumoniae
  • S. bovis (associated with colon cancer)
• HACEK group:
  • Haemophilus
  • Actinobacillus (now known as Aggregatibacter)
  • Cardiobacterium
  • Eikenella
  • Kingella
• Other bacterial causes:
  • Enterococcus
  • Coxellia burnetii
  • Brucella
  • Bartonella
• Fungi:
  • Candida albicans
  • Aspergillus

Noninfective endocarditis etiologies

• Libman-Sacks endocarditis:
  • Due to circulating immune complexes
  • Associated with: 
    • Systemic lupus erythematosus
    • Antiphospholipid syndrome
  • Affects mitral > aortic valve
• Thrombotic (marantic) endocarditis:
  • Malignancy (due to metastases seeding the heart valves)
  • Hypercoagulable states
  • Chronic wasting disease
  • Chronic infections (e.g., tuberculosis)
• Rheumatic endocarditis:
  • Due to antigen-antibody reaction after group A Streptococcus pharyngitis
  • Affects mitral > aortic valve
• Löffler endocarditis:
  • Associated with hypereosinophilic syndrome
  • Due to eosinophilic infiltration and tissue damage
• Iatrogenic trauma to the cardiac valves
• Other autoimmune conditions (rare):
  • Behcet disease
  • Rheumatoid arthritis
  • Systemic scleroderma
  • Vasculitis

Risk Factors and Pathophysiology

Risk factors

The following are risk factors for IE:

• Heart disease:
  • Rheumatic heart disease
  • Valvular abnormalities
  • Congenital defects
  • Presence of a prosthetic valve
• Age > 60 years
• IV drug use (most commonly affects the tricuspid valve)
• Poor dentition
• Implanted devices or catheters
• Immunosuppression
• Previous history of endocarditis

Infective endocarditis

• Predisposing factors:
  • Endocardial abnormality or injury
  • Bacteremia
• Damaged endothelium → platelet and fibrin deposition → adherence by microorganisms
• Proliferation and invasion by organisms → inflammation → vegetation development → valve destruction
• Release of septic emboli → embolic complications and/or metastatic infection

Noninfective endocarditis

• Endothelial injury to the valve leaflets due to:
  • Trauma
  • Circulating immune complexes
  • Cytokines
  • Antigen-antibody reactions
• Platelet activation and deposition occurs (often during a hypercoagulable state).
• Thrombus is interwoven with:
  • Fibrin
  • Immune complexes
  • Mononuclear cells
• Vegetations are easily dislodged → embolic complications

Classification

Infective endocarditis can be further classified based on the clinical course, type of valve, and location.

By clinical course

Acute infectious endocarditis:

• More sudden onset of symptoms
• Progresses more rapidly
• Larger vegetations
• More commonly affects normal valves
• Fatal if not treated promptly
• Most common cause is S. aureus.

Subacute infectious endocarditis (endocarditis lenta):

• More gradual onset of symptoms
• Progresses more slowly (weeks to months)
• Smaller vegetations
• More commonly affects congenitally abnormal or diseased valves
• Patients may survive for months untreated.
• Most common cause is S. viridans.

By valve type

Native valve endocarditis:

• Accounts for 78% of cases
• Further subdivided into:
  • Community acquired (most common)
  • Healthcare associated
  • IV drug use
• Most often associated with:
  • Staphylococcus
  • Streptococcus
  • HACEK organisms

Prosthetic valve endocarditis:

• Further subdivided into:
  • Early: 
    • < 60 days after valve placement
    • Often from contamination during surgery
    • Beware of antimicrobial-resistant organisms.
  • Intermediate: 60–365 days after valve placement
  • Late: 
    • > 1 year after valve placement
    • Usually involves similar organisms to native valve endocarditis
• Associated with a higher risk of complications and mortality

By location

Left-sided endocarditis:

• Mitral valve
• Aortic valve

Right-sided endocarditis (most common in IV drug use):

• Tricuspid valve
• Pulmonic valve

Clinical Presentation

Presentation and course depend on the etiology, location of vegetations, and severity.

General signs and symptoms

The following are more frequently seen in IE than NIE:

• Fever (endocarditis should be suspected in a patient with a fever of unknown origin)
• Night sweats
• Fatigue
• Loss of appetite
• Weight loss
• Myalgias and arthralgias

Cardiac findings

• New or changed cardiac murmur:
  • Mitral regurgitation
  • Tricuspid regurgitation
  • Aortic regurgitation
• Tachycardia
• Arrhythmia:
  • Potentially due to spread of the infection and myocardial abscess formation
  • Results in disruption of the atrioventricular conduction system → conduction delay or heart block

Extracardiac findings

The following are potential findings in IE:

• Splinter hemorrhages:
  • Small areas of red discoloration under the nails
  • Due to microemboli in capillaries
• Osler nodes:
  • Painful red nodules on pads of the fingers and toes
  • Due to immune complex deposition and inflammation
• Janeway lesions:
  • Small, painless, erythematous lesions on the palms or soles
  • Due to septic emboli and microabscesses
• Roth spots:
  • Red spots with pale centers on fundoscopic exam
  • Due to retinal hemorrhages
• Petechiae
• Conjunctiva hemorrhage

Mnemonic

Signs of IE can be remembered with the mnemonic “FROM JANE”:

• Fever
• Roth spots
• Osler nodes
• Murmur
• Janeway lesions
• Anemia
• Nail bed hemorrhage
• Emboli

Systemic embolization

System embolization may occur in both IE and NIE. Often, an embolic event is the only presenting evidence of NIE.

• Transient ischemic attack or stroke: new focal neurologic deficit
• Pulmonary embolism:
  • Dyspnea
  • Pleuritic chest pain
  • Cough
  • Hemoptysis
• Renal infarct:
  • Flank pain
  • Hematuria
• Splenic emboli: LUQ pain

Other complications

• Cardiac:
  • Perivalvular abscess
  • Valve insufficiency
  • Valve rupture
  • Heart failure
  • Pericarditis → cardiac tamponade
• Renal:
  • Glomerulonephritis
  • Antibiotic-induced nephrotoxicity
• Metastatic infections:
  • Splenic abscess
  • Mycotic aneurysm → cerebral hemorrhage
  • Brain abscess or meningitis
  • Septic arthritis
  • Osteomyelitis
  • Renal abscess
  • Pneumonia or lung abscess
• Death: mortality rate up to 40%

Diagnosis

Echocardiogram

• Transthoracic echo (TTE):
  • Used as an initial screening tool
  • A negative study does not exclude the diagnosis.
• Transesophageal echo (TEE):
  • More sensitive, but more invasive
  • Should be performed if TTE is negative and suspicion for endocarditis is high
• Findings:
  • Valvular vegetations:
    • Size
    • Mobility
    • Calcifications
  • Complications:
    • Valvular insufficiency
    • Abscess
• Cannot determine the cause of vegetations (IE versus NIE)

Supporting workup

Laboratory findings:

• The following are nonspecific but may signal IE:
  • Blood cultures:
    • 3 sets should be obtained from different sites.
    • Must be obtained prior to starting antibiotics
    • Negative cultures do not rule out IE.
  • Serology:
    • Consider pursuing if cultures are negative
    • Useful for fastidious organisms
  • CBC:
    • Leukocytosis with left shift
    • Normocytic anemia
  • Inflammatory markers:
    • ↑ Erythrocyte sedimentation rate
    • ↑ CRP
• The following may be useful in NIE:
  • Antinuclear antibodies
  • Lupus anticoagulant
  • Antiphospholipid antibodies

Imaging:

• ECG:
  • Generally normal unless there is extension of the infection
  • A baseline tracing should be performed in all patients.
  • Possible findings:
    • Heart block or atrioventricular dissociation
    • Bundle branch block
• Chest X-ray: 
  • Can rule out other causes of symptoms
  • Potential findings in endocarditis:
    • Septic emboli to the lungs
    • Pulmonary edema and cardiomegaly
• CT:
  • Can be used to assess for sites of metastatic infection
  • May be useful if an underlying malignancy is suspected (for NIE)
• MRI: performed if cerebral embolic events are suspected

Duke diagnostic criteria

The Duke diagnostic criteria is a set of clinical criteria that can aid in the diagnosis of IE.

• Must meet 1 of the following for a definitive diagnosis of IE:
  • 2 major criteria
  • 1 major plus 3 minor criteria
  • 5 minor criteria
• Major criteria:
  • Positive blood cultures (1 of the following):
    • Typical organism for IE in 2 separate blood cultures
    • Persistently positive cultures
    • Single positive culture for Coxiella burnetii
  • Findings of endocardial involvement (1 of the following):
    • By echocardiogram
    • New regurgitation murmur
• Minor criteria:
  • Fever > 38°C (100.4°F)
  • Risk factors:
    • IV drug use
    • Predisposing heart condition
  • Vascular findings:
    • Major arterial emboli
    • Janeway lesions
    • Conjunctival hemorrhages
    • Septic infarcts
    • Mycotic aneurysm
  • Immunologic findings:
    • Osler nodes
    • Roth spots
    • Glomerulonephritis
  • Microbiologic findings by culture that do not meet major criteria

Management

Medical management of IE

Prompt initiation of IV antibiotics is necessary if the patient is acutely ill.

• Recommended consultations:
  • Infectious disease
  • Cardiology
  • Cardiothoracic surgery
• Initiate empiric antibiotics:
  • Native valve: 
    • Vancomycin
    • Ceftriaxone or cefepime
  • Prosthetic valve:
    • Vancomyin
    • Gentamicin
    • Rifampin
• Tailor antibiotics or antifungals based on:
  • Identified pathogen
  • Sensitivities
• Repeat blood cultures every 24 hours until negative.
• Duration of therapy: 6 weeks

Medical management of NIE

• Treatment for the underlying disorder
• Anticoagulation (unfractionated or low-molecular-weight heparin)

Surgical management

• Valve repair or replacement is indicated for:
  • Heart failure
  • Persistent infection
  • Embolic events
  • Prosthetic valve dehiscence
  • Perivalvular abscess
  • Conduction abnormalities
• Implanted hardware removal (e.g., pacemaker) is indicated if:
  • Definite lead or hardware infection
  • Sepsis
  • Pocket infection
  • Persistent bacteremia
  • Staphylococcus bacteremia

Prevention

• Pre-procedure antibiotics: 
  • High-risk procedures:
    • Dental procedures involving manipulation of the gingiva or mucosa
    • Respiratory tract procedures involving biopsy or manipulation of mucosa
  • Prophylaxis indicated for: 
    • Prosthetic valves
    • Unrepaired cyanotic congenital heart disease
    • Repaired congenital heart defect with prosthetic material
    • Prior episode of endocarditis
    • Transplanted heart with valvulopathy
  • Antibiotic options:
    • Amoxicillin (preferred)
    • Cephalexin
    • Clindamycin
• Complete treatment for active infections
• Proper dental hygiene
• Avoid IV drug abuse

Differential Diagnosis

• Cardiac myxoma: a benign tumor and the most common of the primary tumors of the adult heart. Patients may develop signs and symptoms of valvular obstruction, thromboembolism, and arrhythmias. Diagnosis is made by echocardiography, cardiac MRI, or cardiac CT. Complete surgical excision is required because of the substantial risk of embolization and cardiovascular complications, including sudden death.
• Prosthetic valve thrombosis: insufficient anticoagulation after a prosthetic valve is implanted can lead to thrombosis of the valve, which places the patient at risk of thromboembolism and valvular stenosis or regurgitation, leading to heart failure. The diagnosis is made based on the clinical history and echocardiography. Management varies, but may include thrombolytic therapy, appropriate anticoagulation, and potential cardiac surgery.
• Pulmonary embolism: obstruction of the pulmonary arteries, most often due to thrombus migration from the deep venous system. Signs and symptoms include pleuritic chest pain, dyspnea, tachypnea, and tachycardia. Severe cases can result in hemodynamic instability or cardiopulmonary arrest. A chest CT with angiography is the primary method of diagnosis. Management includes oxygenation, anticoagulation, and thrombolytic therapy for unstable patients.
• Myocarditis: inflammation of the heart muscle that can be infectious or noninfectious in etiology. The presentation varies but can include signs and symptoms of heart failure and cardiogenic shock. Echocardiogram may show global systolic dysfunction, cardiac MRI will show edema, and endomyocardial biopsy can give a definitive diagnosis. Treatment focuses on management of heart failure and the underlying cause.
• Pericarditis: inflammation of the outer lining of the heart resulting from infection, autoimmune disease, radiation, surgery, or myocardial infarction. Pericarditis clinically presents with fever, pleuritic chest pain that increases with lying supine, and a pericardial rub on auscultation. An ECG with diffuse ST-segment elevation and an echo showing a pericardial effusion can confirm the diagnosis. Management is supportive.