• Clinical science

Infective endocarditis

Abstract

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

Main pathogens Characteristics
  • Most common cause of acute IE for all groups (including IV drug users and patients with prosthetic valves or pacemakers/ICDs)
  • Affects previously healthy valves
  • Usually fatal within 6 weeks (if left untreated)
  • Most common cause of subacute IE, especially in predamaged native valves (mainly the mitral valve) and in prosthetic valves (≥ 60 days after surgery)
  • Common cause of IE following dental procedures
  • S sanguinis produces dextrans to induce clotting in host, aiding in vegetation formation
  • IE transmitted via infected peripheral venous catheters
  • Common in patients with prosthetic heart valves (most common cause < 60 days following surgery) or pacemakers/ICDs
  • Enterococci, especially Enterococcus faecalis (< 10%)
  • Gram-negative HACEK group
  • Physiological oral pharyngeal flora (∼ 3% of cases of IE)
  • In patients with poor dental hygiene and/or periodontal infection
  • Causes IE in immunosuppressed patients
  • Causes IE in IV drug abusers
  • Cause of IE after cardiosurgical interventions

Risk factors

  • Demographics
    • Male sex
    • Age > 60 years
  • Preexisting conditions
  • 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

  • Pathogenesis: localized infection or contamination → bacteremiabacterial colonization and possible formation of thrombi on valve leaflets and chordae tendineaevalve 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
  • Clinical consequences
  • 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
Course
  • Acute onset
  • Rapid, fulminant progression (days to weeks)
  • More severe constitutional symptoms (e.g., high fever)
  • Insidious onset
  • Slow progression (weeks to months)
  • Less severe constitutional symptoms (e.g., low fever possible, often absent)
  • Early-onset: < 60 days after surgery
  • Late-onset: ≥ 60 days after surgery
Main pathogens

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

Extracardiac manifestations

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

Echocardiography

  • Detects valve vegetations; , new valvular regurgitation, abscess, dehiscence of prosthetic valve
  • Transthoracic echocardiography (TTE) usually performed first (sensitivity: ∼ 75%)
  • 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
  • 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
    1. Predisposition: underlying heart disease or IV drug abuse
    2. Fever ≥ 38°C (100.4F)
    3. Vascular abnormalities
    4. Immunologic disorder
    5. Microbiology

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)
    1. Erosionfibrin deposits on valves
    2. Ulceration
    3. Perforation → adaptation of valve edges not possible
  • Chronic disease (leading to valve insufficiency and valve stenosis)
    1. Erosion → reorganisation of fibrin layer
    2. Granulation tissue → valve scarring/fibrosis
    3. Calcification → thickened and/or shortened tendinous cords


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

  • 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
  • Clinical course
  • 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
  • Native valves
  • IV drug users

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

References:[15][6][16][27][28][29][30]

Prevention

Endocarditis prophylaxis:

References:[14][31]