Infective Endocarditis: Etiology, Pathogenesis, Classification, Diagnosis, and Treatment Methods

Infective endocarditis (IE) is a potentially life-threatening disease associated with inflammation of the endocardium, primarily the valve apparatus of the heart, caused by microbial invasion. Despite the development of antibiotic therapy and modern imaging techniques, the mortality rate of the total number of patients remains high.

Epidemiology

The incidence of infective endocarditis ranges from 3 to 15 cases per 100,000 population per year The incidence increases with age, peaking in those over 60 years due to the accumulation of risk factors such as valve prostheses, cardiac implants, chronic diseases, and frequent medical interventions. Men are about twice as likely to have the disease as women.

In recent decades, there has been a shift in the epidemiological profile: instead of patients with rheumatic heart disease and intravenous drug users, elderly patients, often with implanted valves, prostheses, and pacemakers, now predominate.

Etiology

Various microorganisms can be the cause of IE development.

• Staphylococcus aureus is the most frequent, especially in nosocomial IE and in drug addicts.
• Streptococcus viridans are classic pathogens in native valve disease in patients without obvious risk factors.
• Enterococcus spp. – significant in elderly patients, often associated with urogenital interventions.
• Coagulase-negative staphylococci are frequent causative agents in prosthetic valve infections.
• HACEK group, fungi, gram-negative rod-shaped bacteria, and others are less frequent.

Risk factors include the presence of artificial valves, pacemakers, previous IE, heart defects, intravenous drug use, and chronic hemodialysis.

Pathogenesis

The pathogenesis of infective endocarditis involves several consecutive links:

1. Endothelial damage of valves (for instance, due to turbulent blood flow) → exposure of extracellular matrix.
2. Adhesion of platelets and fibrin → formation of a sterile thrombus (non-bacterial thrombotic endocarditis).
3. Microbial invasion – in transient bacteremia, microorganisms colonize the thrombus.
4. Formation of vegetations – dense clusters of fibrin, inflammatory cells, and bacteria protected from the immune response and antibiotics.
5. Destruction of valvular structures and possible embolization → systemic complications, sepsis, acute heart failure.

Immune mechanisms also contribute to the development of complications such as vasculitis and glomerulonephritis.

The key step is the formation of vegetations that promote persistence of infection and the development of embolic complications.

Classification of infective endocarditis

Clinical manifestations

IE symptomatology is variable and can include both non-specific symptoms and life-threatening conditions.

• General symptoms: fever, sweating, fatigue, weight loss.
• Cardiac signs: new or altered murmur, signs of heart failure.
• Embolic complications: stroke, limb ischemia, infarcts of internal organs.
• Immune manifestations: purpura, Osler’s nodules, Janway’s spots, glomerulonephritis.
• Lesion of the conductive system: blockades, arrhythmias.
• In severe course of IE may develop: septic shock, multi-organ failure.
• In prosthetic endocarditis auscultatory murmurs may be less pronounced, periannular infection is more likely to develop: abscesses, pseudoaneurysms, fistulas.

Diagnosis of infective endocarditis

Laboratory methods:

• General blood analysis: normocytic anemia, leukocytosis, thrombocytopenia.
• COE, CRP: Significantly elevated.
• Procalcitonin: may be moderately elevated.
• Renal findings: creatinine elevation (glomerulonephritis, embolism).
• Hemocultures: ≥3 samples ≥30 min apart before antibiotics (up to 95% sensitivity).
• Serology/PCR: for culture-negative IE (Bartonella, Coxiella, Brucella, etc.).

Instrumental methods:

• Echocardiography (PD echocardiography preferred over TT echocardiography): identifies vegetations, abscesses, pseudoaneurysms, perforations, prosthetic dysfunction. The sensitivity of transesophageal echocardiography exceeds 90%.
• CT: allows detection of abscesses, pseudoaneurysms, emboli and complications of infective endocarditis.
• PET-CT: detects areas of active inflammation and infection; especially valuable in prosthetic endocarditis and presence of devices.
• Brain MRI: often reveals multiple emboli, even in the absence of neurologic symptoms.

Duke criteria

The Duke criteria — an internationally recognized diagnostic scheme for infective endocarditis, combining clinical, microbiological, and imaging findings.

The probability of having IE

• Reliable: two major criteria, or one major and three minor, or five minor.
• Possible: one major and one-two minor, or three minor.
• Excluded: alternative diagnosis, lack of confirmation at autopsy, or complete resolution of symptoms without treatment.

Major criteria

1. Positive hemoculture (one of the following):

• two or more positive blood cultures for typical microorganisms (e.g., S. aureus, S. viridans, Enterococcus spp.) from different samples;
• persistently positive hemoculture: ≥2 positive specimens ≥12 hours apart;
• ≥3 of 4 positive hemocultures taken within 1 hour.

2. Evidence of an endocardial lesion:

• positive EchoCG (PE ECHO or TT ECHO): vegetation, abscess, pseudoaneurysm, perforation;
• a new occurrence of valve failure (insufficiency).

3. Alternatively (ESC 2023):

• positive PET-CT or SPECT for suspected prosthetic IE;
• positive culture from intraoperative valve material.

Minor criteria

1. Predisposing heart disease or intravenous drug administration.
2. Fever ≥38 °C.
3. Vascular phenomena: emboli, infarcts, hemorrhages, Janway’s spots.
4. Immunologic phenomena: Osler’s nodules, Roth’s spots, glomerulonephritis, rheumatoid factor.
5. Microbiologic findings that do not meet the basic criteria: a single positive hemoculture or serologic confirmation of infection typical of IE.

Find more scientifically accurate content on our social media

Subscribe and don’t miss out the latest resources

Treatment of infective endocarditis

Risk factor modification

• Removal/replacement of infected devices and catheters.
• Sanitation of foci of infection (teeth, skin).
• Limiting unnecessary invasive procedures.

Medication therapy

Principles:

• high doses of bactericidal antibiotics;
• prolonged therapy (usually 4-6 weeks);
• consider MIC (minimum inhibitory concentration);
• individualized approach in prostheses, abscesses and resistant strains.

Example Schemes (per ESC 2023):

• Staphylococcus aureus (methicillin-sensitive, MSSA): nafcillin/oxacillin + gentamicin (first week); in prosthetic endocarditis — add rifampicin;
• Staphylococcus aureus (methicillin-resistant, MRSA): vancomycin; in prosthetic endocarditis — add rifampicin;
• Streptococcus spp: penicillin G or ceftriaxone ± gentamicin;
• Enterococcus spp: ampicillin + gentamicin or ampicillin + ceftriaxone (if high resistance to gentamicin).

Surgical Therapy

Indications:

• heart failure due to valve dysfunction (acute severe valve regurgitation);
• uncontrolled infection (abscess, perforation, pseudoaneurysm, ongoing bacteremia >7 days despite adequate antibiotic therapy);
• repeated emboli or large vegetations with episode of emboli (> 10 mm), vegetations >15 mm, especially in left-sided IE even without emboli;
• prosthetic endocarditis;
• fungal IE, as well as IE caused by highly resistant microorganisms.

Contraindications:

• decompensated general condition, multi-organ failure;
• recent massive stroke with hemorrhagic component.

Types of operations (in the vast majority of cases, operations are performed under artificial circulation):

• replacement (prosthetics) of the affected valve;
• removal of vegetations, sanitation of abscesses;
• reconstructive interventions (valve plasty, valve ring plasty, aortic root plasty): if the aortic root is involved, replacement with a conduit (artificial vascular prosthesis with artificial valve) or homograft (human donor valve with a section of ascending aorta) may be necessary;
• removal of infected devices: if electrodes or pacemakers are involved, complete system removal is indicated; in TAVI-endocarditis, the operation is often associated with high mortality, but is indicated in case of treatment failure.