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

Infective endocarditis is a potentially life-threatening disease involving inflammation of the endocardium, predominantly 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 of age 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 epidemiologic profile: instead of rheumatic heart disease and intravenous drug users, elderly patients, often with implanted valves, prostheses, and pacemakers, now predominate.

Etiology

The cause of IE can be caused by a variety of microorganisms, including:

• Staphylococcus aureus is the leader in frequency, especially in hospital-acquired IE and in drug addicts.
• Viridans streptococci are classic causative agents in native valve lesions 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.
• Less frequently – HACEK-group, fungi, gram-negative bacilli, etc.

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. Damage to valve endothelium (e.g. by turbulent blood flow) → exposure of extracellular matrix.
2. Adhesion of platelets and fibrin → formation of sterile thrombus (non-bacterial thrombotic endocarditis).
3. Microbial invasion – in transient bacteremia, microorganisms colonize the clot.
4. Vegetation formation – dense clusters of fibrin, inflammatory cells and bacteria protected from the immune response and antibiotics.
5. Destruction of valve 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

The symptomatology of IE is variable, ranging from nonspecific to life-threatening:

• Common symptoms of infective endocarditis include fever, sweating, fatigue, and 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): Vegetations, abscesses, pseudoaneurysms, perforations, prosthetic dysfunction. Sensitivity of PE echocardiography > 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

An internationally recognized diagnostic scheme for infective endocarditis (IE) that integrates clinical, microbiological, and imaging findings.

The probability of having IE:

• Reliable: 2 major criteria OR 1 major + 3 minor criteria OR 5 minor criteria;
• Possible: 1 major + 1-2 minor OR 3 minor;
• Excluded: alternative diagnosis, lack of confirmation at autopsy, or complete resolution of symptoms without treatment.

Major criteria (Major criteria)

1. Positive hemoculture (one of the following):

• ≥2 positive blood cultures of typical microorganisms (e.g., S. aureus, Streptococcus 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 (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.

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.

Medical 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):

• Staph. aureus (methicillin-sensitive): oxacillin/naphcillin + gentamicin (first week) ± rifampicin (if prosthetic);
• Staph. aureus (MRSA): vancomycin ± rifampicin;
• Streptococcus spp.: penicillin G or ceftriaxone ± gentamicin;
• Enterococcus spp.: ampicillin + gentamicin or + ceftriaxone (if HLR to gentamicin).

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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 c episode of emboli (>10 mm), vegetations >15 mm, especially in left-sided IE even without emboli;
• Prosthetic endocarditis;
• Fungal IE or 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, valve ring, 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: mandatory removal of the entire system. In TAVI-endocarditis: surgery is often highly lethal, but is indicated if therapy is ineffective).