Endocarditis: Causes, Pathophysiology, Symptoms, Diagnosis, Treatment and Prevention

Endocarditis: Causes, Pathophysiology, Clinical Features, Diagnosis and Management

~Introduction

Endocarditis, medically known as infective endocarditis (IE), is a serious and potentially life-threatening infection of the endocardium, the inner lining of the heart, primarily affecting the heart valves. The condition occurs when microorganisms, most commonly bacteria and occasionally fungi, enter the bloodstream and adhere to damaged areas of the heart, forming vegetations composed of fibrin, platelets, and microbes.

Despite advances in diagnosis and therapy, endocarditis continues to be associated with significant morbidity and mortality, especially in patients with predisposing cardiac abnormalities or prosthetic valves. Early detection, accurate diagnosis, and prompt treatment are essential to prevent complications such as heart failure, systemic embolization, and death.

~Historical Background

Endocarditis was first described in the early 19th century, with the microbial cause identified by Sir William Osler in the late 1800s. Osler’s detailed accounts, known as "Osler’s nodes," remain an eponymous feature of the disease. The advent of antibiotics significantly reduced mortality rates, but due to the increasing number of prosthetic heart devices, intravenous drug use, and invasive medical procedures, infective endocarditis remains a major clinical challenge in the modern era.

~Etiology and Causative Organisms

The etiologic agents of endocarditis vary according to the setting, type (acute or subacute), and host factors. The most common causative organisms include:

1. Staphylococcus aureus – The most frequent cause of acute infective endocarditis, especially in intravenous drug users and healthcare-associated infections.

2. Viridans group Streptococci – A common cause of subacute endocarditis, often originating from the oral cavity following dental procedures or poor oral hygiene.

3. Enterococci – Frequently associated with genitourinary tract infections or instrumentation.

4. Coagulase-negative Staphylococci – Often implicated in prosthetic valve endocarditis.

5. HACEK group organisms – Including Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, and Kingella species; these are fastidious Gram-negative bacteria associated with subacute disease.

6. Fungal pathogens (e.g., Candida, Aspergillus) – Occur primarily in immunocompromised patients or those with indwelling catheters.

In some cases, culture-negative endocarditis occurs when the causative organisms are difficult to cultivate or when prior antibiotic therapy suppresses bacterial growth.

~Pathophysiology

Endocarditis typically begins with endothelial damage to the heart’s inner lining or valves, which exposes underlying collagen and tissue factors. This triggers platelet and fibrin deposition, forming a nonbacterial thrombotic endocarditis (NBTE) lesion.

When microorganisms enter the bloodstream (via dental procedures, infections, or IV drug use), they can adhere to these lesions using surface adhesins. Once attached, bacteria become encased in a protective matrix of fibrin and platelets, forming infected vegetations.

These vegetations are resistant to host immune defenses and antibiotic penetration, leading to persistent infection and potential destruction of cardiac tissue. As the infection progresses, complications such as valvular insufficiency, heart failure, abscess formation, and embolization may occur.

~Risk Factors

Several conditions predispose individuals to endocarditis:

1. Pre-existing cardiac abnormalities:

   • Rheumatic heart disease

   • Congenital heart defects (e.g., ventricular septal defect, patent ductus arteriosus)

   • Mitral valve prolapse with regurgitation

   • Prosthetic heart valves

2. Procedural or medical risk factors:

   • Invasive dental or surgical procedures

   • Long-term intravenous catheterization

   • Hemodialysis

   • Pacemaker or defibrillator implantation

3. Lifestyle and systemic conditions:

   • Intravenous drug use

   • Immunosuppression or HIV infection

   • Diabetes mellitus

4. Other causes:

   • Poor oral hygiene and chronic periodontitis

~Classification of Endocarditis

Endocarditis can be classified based on several criteria:

1. Based on Etiology

• Infective Endocarditis (IE): Caused by microbial infection (bacteria, fungi).

• Non-Infective Endocarditis: Includes marantic endocarditis and Libman-Sacks endocarditis, often associated with malignancy or autoimmune disorders.

2. Based on Clinical Course

• Acute Endocarditis: Rapid onset, aggressive course, often caused by Staphylococcus aureus; leads to severe valve destruction and systemic toxicity.

• Subacute (Chronic) Endocarditis: Slower progression, caused by less virulent organisms like Streptococcus viridans; symptoms develop over weeks or months.

3. Based on Valve Involvement

• Native Valve Endocarditis (NVE): Occurs on natural heart valves.

• Prosthetic Valve Endocarditis (PVE): Occurs on artificial valves; can be early (within 60 days post-surgery) or late (after 60 days).

• Right-sided Endocarditis: Often linked to intravenous drug use; affects tricuspid valve.

• Left-sided Endocarditis: More common overall; involves mitral or aortic valves.

~Clinical Manifestations

The symptoms of endocarditis vary widely depending on the organism, the presence of underlying heart disease, and whether the disease is acute or subacute.

General Symptoms:

• Persistent fever (most common)

• Chills and night sweats

• Fatigue, malaise, and weight loss

• Loss of appetite

Cardiac Symptoms:

• New or changing heart murmur

• Signs of congestive heart failure (dyspnea, edema, orthopnea)

Vascular and Immunologic Manifestations:

• Petechiae: Small hemorrhagic spots on skin, conjunctiva, or mucous membranes.

• Splinter hemorrhages: Linear streaks beneath fingernails.

• Osler’s nodes: Tender nodules on fingers or toes.

• Janeway lesions: Non-tender lesions on palms or soles.

• Roth spots: Retinal hemorrhages with pale centers.

Systemic Embolic Events:

• Cerebral emboli → stroke, seizures, or focal neurological deficits.

• Renal infarction → hematuria or flank pain.

• Pulmonary emboli (in right-sided IE) → cough, pleuritic pain, hemoptysis.

• Splenic infarction or abscess → left upper quadrant pain.

~Complications

1. Cardiac Complications

   • Valvular insufficiency or perforation

   • Myocardial abscess formation

   • Heart failure due to valvular dysfunction

   • Pericarditis

2. Embolic Complications

   • Stroke and transient ischemic attacks

   • Pulmonary embolism (especially in tricuspid involvement)

   • Renal and splenic infarctions

3. Immunologic and Systemic Complications

   • Glomerulonephritis

   • Vasculitis

   • Septic shock

4. Death

   • Occurs in severe cases with delayed diagnosis or untreatable infection.

~Diagnosis

The diagnosis of infective endocarditis requires a combination of clinical, microbiological, and imaging criteria. The Modified Duke Criteria remain the gold standard.

1. Major Criteria:

• Positive blood cultures with typical organisms for IE (e.g., S. aureus, Streptococcus viridans).

• Evidence of endocardial involvement on echocardiogram:

  • Vegetation

  • Abscess

  • New valvular regurgitation

2. Minor Criteria:

• Predisposing heart condition or intravenous drug use

• Fever >38°C

• Vascular phenomena (emboli, Janeway lesions, hemorrhages)

• Immunologic phenomena (Osler nodes, glomerulonephritis)

• Microbiological evidence not meeting major criteria

Diagnosis:

• Definite IE: 2 major, or 1 major + 3 minor, or 5 minor criteria.

• Possible IE: 1 major + 1 minor or 3 minor criteria.

3. Laboratory Tests:

• Complete blood count (may show anemia, leukocytosis)

• Elevated ESR and CRP

• Positive rheumatoid factor

• Urinalysis showing microscopic hematuria

4. Imaging:

• Echocardiography:

  • Transthoracic Echo (TTE): Initial non-invasive test.

  • Transesophageal Echo (TEE): More sensitive for detecting small vegetations or prosthetic valve involvement.

• CT/MRI may be used to identify embolic or abscess complications.

~Treatment

The mainstay of treatment for infective endocarditis involves prolonged intravenous antibiotic therapy, with or without surgical intervention.

1. Medical Management

Antibiotic therapy is tailored based on culture and sensitivity results and typically lasts 4–6 weeks.

Empirical Therapy (Before culture results):

• Combination of Vancomycin + Ceftriaxone or Gentamicin to cover both Gram-positive and Gram-negative organisms.

Specific Regimens:

• Streptococcal IE: Penicillin G or Ceftriaxone ± Gentamicin

• Staphylococcal IE: Nafcillin or Oxacillin for MSSA; Vancomycin for MRSA

• Enterococcal IE: Ampicillin + Gentamicin or Vancomycin-based regimen

• Fungal IE: Amphotericin B ± surgical valve replacement

Close monitoring of renal function, drug toxicity, and blood cultures during therapy is essential.

2. Surgical Management

Surgery is indicated in:

• Severe heart failure due to valve destruction

• Persistent infection despite antibiotics

• Large vegetations (>10 mm) with recurrent emboli

• Prosthetic valve infection

• Myocardial abscess formation

Surgical options include valve repair or replacement with mechanical or bioprosthetic valves.

~Prognosis

The prognosis of infective endocarditis varies depending on the causative organism, promptness of diagnosis, and patient’s underlying health. Mortality ranges between 15–30% despite modern therapy.

Better outcomes are seen in streptococcal infections compared to staphylococcal or fungal infections. Complications like heart failure, embolization, and renal failure worsen prognosis.

~Prevention

Preventing endocarditis involves identifying at-risk individuals and reducing bacteremia through hygiene and prophylaxis.

1. Antibiotic Prophylaxis

Recommended before invasive dental or surgical procedures in:

• Prosthetic heart valve recipients

• Previous history of IE

• Certain congenital heart diseases

Common prophylactic regimen:

• Amoxicillin 2 g orally, 30–60 minutes before the procedure.

2. Other Preventive Measures

• Maintaining good oral hygiene

• Avoiding unnecessary catheterization

• Proper aseptic techniques during medical procedures

• Harm reduction strategies for intravenous drug users

~Recent Advances and Research

Recent developments include:

• Molecular diagnostic tools such as PCR for culture-negative cases.

• 3D echocardiography and cardiac MRI for improved visualization.

• Novel antimicrobial therapies and biofilm-targeting agents.

• Minimally invasive surgical approaches for valve repair.

Ongoing research aims to improve early detection, enhance antibiotic efficacy, and develop better preventive strategies.

~Conclusion

Endocarditis remains a serious cardiovascular infection that demands early recognition and aggressive treatment. Despite advancements in diagnostics and therapeutics, it continues to carry substantial morbidity and mortality. A multidisciplinary approach involving cardiologists, infectious disease specialists, and cardiac surgeons is vital for optimal outcomes.

Public awareness, timely medical intervention, and adherence to preventive measures can significantly reduce the burden of this life-threatening condition.