Infective endocarditis

Definition

Infective endocarditis (IE) is an infection of the endocardium, usually of the heart valves. The starting point is generally a sterile fibrin-platelet deposit on damaged endothelium, which becomes colonised during bacteremia and grows into a vegetation. It is distinguished from non-infective endocarditis with sterile thrombi on the valves, which can progress to infective endocarditis.

Classification

• Subacute bacterial endocarditis: insidious over weeks to months, often without a recognizable portal of entry; mostly streptococci (especially viridans streptococci) or enterococci, usually on previously abnormal valves.
• Acute bacterial endocarditis: rapid over days, portal of entry often evident; mostly Staphylococcus aureus, group A beta-hemolytic streptococci, pneumococci or gonococci; can also affect normal valves.
• Prosthetic valve endocarditis: in 1–2 % of patients within the first year after valve implantation, then about 0.5 % per year; early infections (under 2 months) mainly due to Staphylococcus epidermidis, diphtheroids, coliform bacilli or fungi, late infections mostly due to streptococci, S. epidermidis and gram-negative HACEK organizms.
• Right-sided endocarditis: about 5–10 % of cases (tricuspid or pulmonary valve), much more common with intravenous drug use.

Occurrence & epidemiology

Infective endocarditis occurs at any age; men are affected about twice as often as women. Incidence increases with age. The highest risk is found in people who use intravenous drugs, people with immunodeficiency, prosthetic valves or other intracardiac implants; indwelling intravascular catheters also increase the risk.

Aetiopathogenesis

• Pathogens: 80–90 % of cases are caused by streptococci or Staphylococcus aureus; most of the rest by enterococci, gram-negative bacilli, HACEK organizms (Hemophilus, Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae) or fungi. Staphylococcal and enterococcal endocarditis are increasing, streptococcal endocarditis is decreasing.
• Predisposing cardiac findings: congenital heart defects, rheumatic valve disease, bicuspid or calcified aortic valve, mitral valve prolapse, hypertrophic cardiomyopathy, previous endocarditis; especially prosthetic valves and other intracardiac implants.
• Source of bacteremia: distant foci of infection (skin abscess, inflamed gums, urinary tract infection), central venous catheters, needle puncture sites in drug use; asymptomatic bacteremia during dental and other procedures, and in gingivitis even during toothbrushing or chewing.
• Pathogenesis in three steps: bacteremia, adhesion to damaged endothelium, colonisation with inflammation and a mature vegetation. Many organizms form protective biofilms.

Clinical features

• General: in subacute disease initially non-specific with low-grade fever, night sweats, fatigability, malaise and loss of weight, possibly rigors and arthralgia. In acute and prosthetic valve endocarditis, fever (78 %), heart murmur (65 %) and heart failure (27 %) are the most frequent findings at presentation.
• Cardiac and local: new or changed regurgitant murmur; myocardial abscesses with conduction disturbances; sudden severe valvular regurgitation with heart failure; with prostheses ring abscesses, dehiscence and obstruction.
• Emboli: about 35 % have CNS involvement (TIA, stroke, toxic encephalopathy, brain abscess or subarachnoid hemorrhage from a ruptured mycotic aneurysm); renal and splenic infarcts with flank or upper abdominal pain; in right-sided endocarditis septic pulmonary emboli with cough, pleuritic pain and hemoptysis.
• Skin, mucosa and eye: petechiae, painful Osler nodes on finger and toe pads, painless hemorrhagic Janeway lesions on palms and soles, splinter hemorrhages under the nails, conjunctival hemorrhages, Roth spots of the retina.
• Others: splenomegaly and clubbing with prolonged disease; immune complex glomerulonephritis.

Histology

Endocarditis is definite when microorganizms are seen histologically in, or cultured from, vegetations – for example in valve tissue, embolic material or at autopsy. Because vegetations are usually not available for examination, the diagnosis generally relies on clinical criteria.

Diagnosis

Investigations

• Blood cultures: at least 2, ideally 3 sets (each aerobic and anaerobic) from separate fresh venepunctures, independent of fever spikes, because bacteremia is usually continuous. Without prior antibiotic therapy, at least one culture is positive in 90 % when more than 2 samples are taken.
• If cultures are negative: serology (e.g. Coxiella burnetii, Bartonella, Brucella), special culture media, PCR, possibly metagenomic sequencing.
• Laboratory: normocytic normochromic anemia, leukocytosis, raised ESR, hypergammaglobulinemia, circulating immune complexes, rheumatoid factor; microscopic hematuria and occasionally red cell casts in the urine.
• Echocardiography: TTE first (sensitivity 50–90 %, specificity above 90 %); TOE with a sensitivity of 90–100 %, especially with prostheses, non-diagnostic TTE and to detect perforations, abscesses and fistulae.
• Further imaging: CT for paravalvular abscesses and mycotic aneurysms; FDG PET/CT especially with prostheses and implants and to detect septic emboli.

Duke-ISCVID criteria 2023

Major criteria:

• Microbiology: at least two separate positive blood culture sets with organizms typical of endocarditis or at least three with organizms that rarely cause it; detection of Coxiella burnetii, Bartonella or the agent of Whipple's disease in blood by PCR; an IgG titer above 1:800 against Coxiella burnetii or Bartonella henselae/quintana; one positive blood culture for Coxiella burnetii
• Imaging: vegetation, valve perforation or aneurysm, abscess, pseudoaneurysm or intracardiac fistula on echocardiography or cardiac CT; significant new valvular regurgitation; new partial dehiscence of a prosthesis; abnormal activity on FDG PET/CT at a native valve or prosthesis (at least 3 months after implantation), leads or other foreign material
• Direct finding: evidence of endocarditis on direct inspection of the opened heart

Minor criteria:

• Predisposition: previous endocarditis, prosthetic valve or valve repair, congenital heart disease, more than mild regurgitation or stenosis, intracardiac implant, hypertrophic obstructive cardiomyopathy, intravenous drug use
• Fever of 38.0 °C or higher
• vascular phenomena: arterial embolism, septic pulmonary infarction, cerebral or splenic abscess, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, Janeway lesions, purulent purpura
• immunological phenomena: immune complex glomerulonephritis, Osler nodes, Roth spots, rheumatoid factor
• detection of an organizm that does not meet a major criterion
• abnormal FDG PET/CT activity within 3 months after implantation
• new regurgitant murmur if echocardiography is not available

Definite endocarditis: pathological criteria or 2 major, 1 major plus 3 minor, or 5 minor criteria. Possible endocarditis: 1 major plus 1 minor criterion or 3 minor criteria. The criteria achieve a sensitivity of 84 % and a specificity of 94 %.

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Further reading (open access)

1. MSD Manual Professional: Infective Endocarditis
2. StatPearls: Infective Endocarditis

Cross-references