- Clinical science
Infective endocarditis
Summary
Infective endocarditis (IE) is an infectious inflammation of the endocardium that affects the heart valves. The condition is a result of bacteremia, which is most commonly caused by dental procedures, surgery, distant primary infections, and nonsterile injections. IE clinically presents with either an acute or subacute course. Acute disease is usually caused by Staphylococcus aureus and causes rapid endocardium destruction. Subacute progression is most commonly caused by viridans streptococci species and generally affects individuals with pre-existing damage to the heart valves, structural heart defects, or the presence of prosthetic valves. Unlike acute disease, in which patients develop symptoms over a period of hours to days, subacute disease is associated with a progression of symptoms over weeks to months. Clinical features include constitutional symptoms (fatigue, fever/chills, malaise) in combination with signs of pathological cardiac changes (e.g., new or changed heart murmur, heart failure signs) and possibly manifestations of subsequent damage to other organs (e.g., glomerulonephritis, septic embolic stroke). Diagnosis is made based on the Duke criteria, whose main features include positive blood cultures and evidence of endocardial involvement in echocardiography. Initial treatment of IE consists of empiric IV antibiotic therapy, which is then adapted to blood culture results and continued for four to six weeks. Prophylaxis is only administered in specific circumstances, e.g., in patients with preexisting heart conditions undergoing dental or surgical procedures. If left untreated, infective endocarditis can be fatal within a few weeks.
Etiology
Pathogens
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Risk factors
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Demographics
- Male sex
- Age > 60 years
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Preexisting conditions
- Previous IE
- Predamaged or prosthetic heart valves
- Congenital heart defects
- Need for chronic hemodialysis
- Impaired immune function (e.g., HIV infection)
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Bacteremia
- Infected peripheral venous catheters, surgery, dental procedures
- Non-sterile venous injections (e.g., IV drug abuse)
- Bacterial infections of various organs (e.g., UTIs, spondylodiscitis)
References:[1][2][3][4][5][6][7][8][9][10][11][12][13]
Pathophysiology
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Pathogenesis: localized infection or contamination → bacteremia → bacterial colonization and possible formation of thrombi on valve leaflets and chordae tendineae → valve destruction with loss of function
- Preexisting valvular endothelial damage or prosthetic valves predispose to bacterial colonization, especially of those that cause subacute IE
- Frequency of valve involvement: mitral valve > aortic valve > tricuspid valve > pulmonary valve
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Clinical consequences
- Bacterial thromboemboli from bacterial vegetation → vessel occlusion with infarctions
- Formation of immune complexes and antibodies against tissue antigens → glomerulonephritis; , Osler nodes
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Therapeutic consequences
- Lack of valve vascularization requires antibiotic treatment for several weeks
References:[14][15][6][16]
Clinical features
Course of disease
Acute bacterial endocarditis | Subacute bacterial endocarditis | Prosthetic valve endocarditis | |
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Constitutional symptoms
- Fever and chills (∼ 90% of cases), tachycardia
- General malaise, weakness, night sweats, weight loss
- Dyspnea; , cough, pleuritic chest pain
- Arthralgias, myalgias
Cardiac manifestations
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New heart murmur development or change to a preexisting one
- Mitral valve regurgitation → holosystolic murmur, loudest at the heart's apex, and radiates to the left axilla
- Tricuspid valve regurgitation → holosystolic; murmur; loudest at the left sternal border ; seen in IV drug users; and concomitant HIV infection; , immunosuppressed patients,; and patients with central venous catheters
- Aortic valve regurgitation → early diastolic murmur; loudest at the left sternal border
- Signs of progressive heart failure (e.g., dyspnea, edema)
- Signs of acute cardiac decompensation (pulmonary edema)
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Arrhythmias
- Suspect perivalvular abscess in patients with infective endocarditis who develop a new conduction abnormality (e.g., a third-degree atrioventricular block)
Extracardiac manifestations
- These manifestations are mainly caused by bacterial microemboli and/or the precipitation of immune complexes .
- Petechiae; especially splinter hemorrhages (hemorrhages underneath fingernails)
- Janeway lesions: non-tender, erythematous macules on palms and soles; (due to microemboli and microabscesses with neutrophilic capillary infiltration)
- Osler nodes: painful nodules on pads of the fingers and toes
- Roth spots: retinal hemorrhages with pale centers
- Signs of acute renal injury, including hematuria and anuria
- Splenomegaly and possible LUQ pain
- Neurological manifestations (e.g., seizures, paresis)
- Signs of pulmonary embolism (e.g., dyspnea)
- Possible arthritis
Infective endocarditis should always be considered as a cause of fever of unknown origin (FUO), especially if a new heart murmur develops!
FROM JANE - Fever, Roth's spots, Osler nodes, Murmur, Janeway lesions, Anemia, Nail bed hemorrhage, Emboli
References:[15][6][17][18][19][20][21][22][23]
Diagnostics
Laboratory studies
- Best initial test: blood cultures
- Leukocytosis (with left shift); , ↑ ESR, ↑ CRP
Echocardiography
- Detects valve vegetations; , new valvular regurgitation, abscess, dehiscence of prosthetic valve
- Transthoracic echocardiography (TTE) usually performed first (sensitivity: ∼ 75%)
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Transesophageal echocardiography (TEE) to confirm findings; higher sensitivity (> 90%) than TTE
- More likely to detect complications (abscess, leaflet perforation)
(Modified) Duke criteria
- The Duke criteria help to diagnose infective endocarditis. To confirm the diagnosis, one of the following requirements must be met:
- Two major criteria
- One major and three minor criteria
- Five minor criteria
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Major diagnostic criteria
- Two separate blood cultures positive for typical pathogens (see “Etiology” above)
- Evidence of endocardial involvement in echocardiography
- A new valvular regurgitation (worsening of a pre-existing murmur is not sufficient)
- Minor diagnostic criteria
Only negative findings on transesophageal echocardiography (TEE) can reliably rule out endocarditis, as transthoracic echocardiography (TTE) is not sensitive enough!
References:[14][15][6][19][24]
Pathology
Pathogenesis
- Acute disease (leading to valve insufficiency, septic embolic infarcts, tendinous cord rupture)
- Chronic disease (leading to valve insufficiency and valve stenosis)
References:[6]
Differential diagnoses
Nonbacterial thrombotic endocarditis
- Rare, non-infectious form of endocarditis due to sterile platelet thrombus formation on the heart valves (usually aortic and mitral valves)
- Most commonly associated with underlying malignancy, hypercoagulable states, or rheumatologic conditions (SLE, rheumatoid arthritis, etc.)
- Compared to infectious endocarditis, vegetations are easily dislodged and embolization is common; most patients are asymptomatic until embolization occurs
- Definitive diagnosis can only be made pathologically: shows vegetations on either surface of the valve that are composed of immune complexes, mononuclear cells, and thrombi interwoven with fibrin strands
- Libman-Sacks endocarditis: describes especially large vegetations, also referred to as verrucous vegetations
Prosthetic valve thrombosis
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Etiology
- Occurs if insufficient anticoagulatory therapy after valve replacement
- Usually affects mechanic valves
- Rare if anticoagulation is adequate
- Presence of a cardiac defect raises the risk of recurrent endocarditis
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Clinical course
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Signs of acute heart failure
- Left heart failure: dyspnea and cough
- Right heart failure: edema and jugular venous distention
- Deterioration of general condition, cardiac arrhythmias, cerebral emboli (stroke)
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Signs of acute heart failure
- Diagnostics: transesophageal echocardiography
- Treatment: anticoagulation and fibrinolysis, surgical valve replacement
References:[25][26]
The differential diagnoses listed here are not exhaustive.
Treatment
Empirical therapy
Condition/Patient group | Antibiotic therapy |
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If infective endocarditis is suspected: 1. Obtain blood cultures → 2. Start empiric antibiotic therapy immediately → 3. Adapt the therapy according to culture results
Targeted therapy
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Drug of choice
- First-line: 3rd or 4th generation IV cephalosporin (e.g., ceftriaxone, cefotaxime)
- Second-line : ampicillin-sulbactam , IV fluoroquinolone
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Duration of therapy
- Native valve infectious endocarditis: 4 weeks
- Prosthetic valve endocarditis: 6 weeks
References:[15][6][16][27][28][29][30]
Prevention
- Indicated for high-risk patients ; undergoing procedures with risk of bacteremia
- Regimens
- Usually PO amoxicillin (administer 1 hour before procedure)
- Patients who are unable to take oral medication: IV ampicillin
- Patients with penicillin allergy: PO clarithromycin or azithromycin
References:[14][31]