Ontology of Infective Endocarditis Sivaram Arabandi, MD

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Infective endocarditis is an infection of the endocardium of the heart. It is a complex disease presenting with a constellation of symptoms and signs. In its acute form, it evolves rapidly and can lead to death within weeks.

Endocarditis Exudative and proliferative inflammatory changes in the endocardium, characterized by vegetations.

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Infective Endocarditis (IE) Invasion and multiplication of microorganisms in the endocardium.

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Echo: Vegetations

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SLIDE: Echo: Vegetations

This TEE image shows large mobile vegetations on the aortic valve cusps.

Vegetations

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SLIDE: This is the surgeon’s view of the same vegetations (at the arrow).

Echo: Extra-Aortic abscess

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SLIDE: Echo: Extra-Aortic Abscess In the same patient, this image shows an extra-aortic cavity suggesting an abscess anteriorly.

Abscess cavity

LVOT

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SLIDE: Abscess cavity Again, the surgeon’s view of the same abscess

Echo: Perforation

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SLIDE: Echo: Mitral leaflet perforation Color echo demonstrating mitral regurgitation through the perforation.

Perforation - mitral leaflet

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SLIDE: Mitral leaflet perforation and the perforation as seen at surgery.

Echo: Aorta-RA fistula

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SLIDE: Echo: Aorta – RA fistula At 7 o’clock, the color image demonstrates a fistula between the aortic root and the right atrium.

Aortic-RA fistula

TV

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SLIDE: Aorta – RA fistula Surgeon’s view from the right atrium of the break-through just by the A-V node in Koch’s triangle.

Endocarditis classification • • • • •

Temporal evolution: Acute, Subacute Cause: Infective,Non-infective Site: Valves, chambers State: Active, Inactive Valve type: Native, Prosthetic

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Endocarditis classification There are several ways in which endocarditis is classified. Each provides useful criteria for understanding the disease, its management as well as prognosis. Temporal evolution:

Acute endocarditis - a severe form of IE that manifests in days or weeks as a febrile illness. It is caused by virulent organisms like staphylococci.

Subacute endocarditis - develops slowly over weeks or months. Cause:

Infective endocarditis - Invasion and multiplication of micro-organisms in the endocardium.

NonBacterial Thrombotic Endocarditis (NBTE) - an uninfected thrombus as result of endocardial injury, hyper-coagulable state etc. The thrombus can serve as site of bacterial attachment during bacteremia. Common predisposing conditions of NBTE are regurgitation, stenosis, VSD and other congenital cardiac malformations. Marantic endocarditis is a result of a hypercoagulable state often due to chronic diseases, malignancy etc. Sites:

Aortic Valve, Mitral Valve, Pulmonic Valve, Tricuspid Valve, Atrial surface, Ventricular surface, Chordae

Distal Aorta (in Coarctation of aorta)

Pulmonary Artery (in PDA) State:

Active endocarditis - term indicating the active infection as evidenced by positive blood cultures, local cardiac manifestations like abscesses, fistulae etc., and patient on antimicrobial therapy

Inactive or Healed endocarditis - absence of obvious infection generally following treatment and eradication of microorganisms. Cardiac sequelae like stenosis, regurgitations,

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Pathology

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Microorganisms, pathogenesis, morphological changes, transmission of Infective Endocarditis

Micro-organisms • Bacteria • Fungi • Viruses • Rickettsia

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IE is caused by bacteria in most cases, occasionally by fungi and rarely by viruses etc. The temporal course of IE is dictated by the microorganism involved. Bacteria:

- Staph. aureus, beta-hemolytic streptococci cause acute infection

- Streptococcus viridans, enterococci, HACEK group cause a subacute infection

- Bartonella and C. burnetti (Q fever) cause particularly indolent infections Fungal infections:

- Candida

Pathogenesis • endothelial injury • hypercoagulable state • altered immune system • bacteremia • transmission

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Several factors contribute to the development of IE - factors like endothelial injury, hypercoagulable state, altered immune system, bacteremia. Normal endothelium is quite resistant to infection (by most bacteria) and to thrombus formation. Endothelial injury: can be the result of

1. pre-existing conditions like rheumatic valvulitis, calcification

2. hemodynamic factors such as high velocity jets (PDA, small VSD, mitral regurgitation, bicuspid aortic valve etc)

3. catheter trauma -> leads to either direct infection by virulent organisms or to thrombus formation (NBTE). The thrombus can be a site for bacterial attachment during transient bacteremia. Hypercoagulable state: An uninfected thrombus can form in hypercoagulable states - here it is called as marantic endocarditis. This is seen in patients with malignancies or with chronic conditions. Altered immune system: studies have linked circulating immune complexes (CICs) with IE. CICs are found in Roth spots or Janeway lesions. Bacteremia: Transient bacteremia is fairly common (> 60 % of normal individuals). The bacterial load is small and without predisposing factors, does not result in IE. Infective endocarditis can occur in normal patients when there is:

1. virulent infection - Staphylococcus aureus, Streptococcus viridans

2. overwhelming sepsis

3. IV drug use

4. indwelling catheters (chronic hemodialysis)

5. prolonged antibiotic therapy -> fungal infections

Morphology • sites • vegetations • cellulitis • abscess, abscess cavity, pseudoaneurysm • fistula • tear, perforation • chord rupture

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The sites of IE lesions depends on the etiology and are seen on the low pressure side of jets of blood. IE related to IV drug use occurs mostly on the right side - involving the Tricuspid valve in half the cases, Aortic or Mitral valves in the remainder. Vast majority of native endocarditis not related to drug use occur on the left side. Aortic regurgitation -> ventricular surface of aortic valve Mitral regurgitation -> atrial surface of mitral valve Pulmonary regurgitation -> ventricular surface of pulmonary valve Tricuspid regurgitation -> atrial surface of tricuspid valve Ventricular septal defect (VSD) -> right ventricle Infective endarteritis Coarctation of aorta -> aorta distal to the coarctation Patent ductus arteriosus (PDA) -> pulmonary artery Vegetations are the typical lesions of infective endocarditis.

Clinical Features

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Symptoms • fever with chills and sweats • anorexia • joint pains, backache • H/o injection drug use

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Signs • heart murmur • new/worsened regurgitant murmur

• evidence of emboli • splenomegaly • peripheral manifestations • Osler nodes, subungual hemorrhages, Janeway lesions, Roth spots, petechiae

• neurological manifestations • stroke, meningitis, seizures

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Osler nodes - Small, painful nodules on the pads of fingers or toes. They are transient and appear for hours or days. Janeway lesion - painless erythematous lesions of the palms or soles. Roth spots - Small retinal hemorrhages with a pale center.

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Labs • anemia, leukocytosis • hematuria • ESR, C-reactive protein • serum complement • circulating immune complexes • rheumatoid factor • serologic tests for Brucella, Bartonella, Legionella, C. burnetti

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Blood culture • isolation of micro-organism • antimicrobial susceptibility • treatment plan

• blood sample • multiple samples • multiple sites

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Blood culture is one of the primary modalities of investigation of IE. Blood samples are collected a number of times over several hours from different sites to increase the chances of isolating the causative organism.

Echo Trans thoracic echo [TTE] Trans esophageal echo [TEE] Findings: • Sites • Vegetations • Complications • Cardiac function

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Echo allows for the anatomic confirmation of Infective Endocarditis

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Diagnosis

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Diagnosis • constellation of findings • definitive diagnosis - biopsy (of vegetations) • Duke criteria • Staging

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IE is a complex disease and presents with a wide variety of findings. As such it can be difficult to diagnose with certainty. A definitive diagnosis can only be made from the vegetations obtained at surgery, autopsy or from biopsy of a peripheral lesion. In order to improve the specificity and sensitivity of diagnosis, a set of criteria were proposed at Duke University.

Duke criteria Major criteria: • Positive blood culture for IE • Typical microorganisms for IE from two separate blood cultures • Persistently positive blood culture

• Evidence of endocardial involvement • positive echo findings of IE • new valvar regurgitation

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Duke criteria take into account major and minor symptoms and signs, echo findings and other factors.

Duke criteria Minor criteria: • Predisposition –predisposing heart condition, IV drug use

• Fever > 38o C • Vascular phenomena –major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, Janeway lesions

• Immunologic phenomena –glomerulonephritis, Osler nodes, Roth spots, rheumatoid factor

• Microbiologic evidence • Echo 31

Duke criteria take into account major and minor symptoms and signs, echo findings and other factors.

Duke criteria Diagnostic of IE • 2 major criteria • 1 major and 3 minor criteria • 5 minor criteria

Possible IE • 1 major and 1 minor criteria • 3 minor criteria

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Staging • complex disease • complexity of cases • new treatments • outcomes

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Why is it important?

Staging Classification • anatomical sites • vegetations - sites, sizes • lesions - vegetations, cellulitis, tear, perforation, chordae rupture, abscess, cavity, pseudoaneurysm, fistula, AV node/bundle destruction • measurements - circumferential extent, cavity depth • Prosthetic valve - restriction of disc/ball, paraprosthetic leak, unstable/rocking valve

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Staging Stage: • Early • Advanced

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Treatment

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Treatment of IE involves medical management (primarily antibiotics), surgery and supportive therapy

Treatment Anti-microbials • Penicillin G • Ampicillin • Ceftriaxone • Vancomycin • Nafcillin • ....

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Ideally, anti-microbial therapy should be based on identification of the microorganism responsible as well as its anti-microbial susceptibility.

Treatment Surgical procedures • remove infected tissue and drain abscesses • restore/reconstruct – Valve repair/replacement – endocardium replacement – repair of VSD, PDA, Coarctation of Aorta

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Surgery Indications 1. valve dysfunction with mod-severe CHF 2. antimicrobial therapy ineffective 3. relapse after optimal antimicrobial therapy 4. dehisced/unstable prosthetic valve 5. Staph. aureus prosthetic valve endocarditis 6. perivalvular extension of infection 7. large (> 10 mm) hypermobile vegetations 8. persistent unexplained fever (> 10 days) in culture negative native valve endocarditis

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Problem areas Flow charts • when should Echo be done?

Diagnostic criteria Staging Indications for • Echo, Surgery, ...

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Acknowledgements SemanticDB project Chime Ogbuji Chris Pierce

Heart and Vascular Institute Dr. Eugene Blackstone

Infectious Diseases Institute Dr. Steve Gordon

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