Infective Endocarditis

Slide 1 · Infective Endocarditis

Etiology · pathogenesis · morphology · clinicopathologic diagnosis

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Define infective endocarditis and describe infected vegetations.

Link microbial virulence and substrate to clinical tempo.

Identify the major morphologic lesions and complications.

Integrate cultures, imaging and clinical findings using Duke criteria.

Slide 3 · Infective endocarditis: Core definition

Microbial infection involves valve tissue or mural endocardium.

Vegetations comprise thrombotic debris and microorganisms.

Underlying cardiac tissue can be destructively involved.

Although bacterial IE predominates, fungi and other microbes occur.

Slide 4 · The principal anatomic targets

Native valves

Aortic and mitral valves are the most common sites.

Right-sided valves

May be infected, particularly with injection drug use.

Mural endocardium

Infection is not strictly confined to valve leaflets.

Slide 5 · Disease components are causally linked

Bloodstream seeding

Valvular/endocardial infection

Infected vegetation

Tissue damage ± embolism

Infection and thrombus formation interact; The vegetation is not a sterile clot.

Slide 6 · Acute versus subacute: Traditional clinical pattern

Acute IE

More virulent organisms, classically S. Aureus

Can infect previously normal valves

Rapid, destructive course

Subacute IE

Less virulent organisms, often viridans streptococci

Usually deformed valve substrate

Indolent course over weeks to months

Slide 7 · Acute and subacute form a continuum

The distinction reflects tempo, virulence and often valve substrate.

There is no absolute dividing line between the two forms.

Cases with mixed features are recognized.

Classify the actual clinical course rather than assuming an organism from tempo.

Slide 8 · Acute IE: Rapid destruction

Classically, S. Aureus can seed a previously normal valve.

Vegetations and tissue damage may develop rapidly.

Antibiotic therapy alone may not suffice in destructive cases.

Surgery may become necessary; Morbidity can remain substantial.

Slide 9 · Subacute IE: Persistent infection

Often involves valves already abnormal or scarred.

Viridans-group streptococci are the classic lower-virulence example.

Progression may extend over weeks or months.

Less destruction and a greater chance of medical cure are typical.

Slide 10 · Clinical tempo is not just a clock

Microbial virulence

Valve susceptibility

Rate of tissue destruction

Observed clinical course

These determinants overlap; Presentation is variable.

Slide 11 · Acute and subacute IE: Morphology–tempo relationship

Feature

Acute pattern

Subacute pattern

Illustrative pathogen

Staphylococcus aureus

Viridans streptococci

Common substrate

May be normal

Frequently pre-damaged

Clinical onset

Abrupt, stormy

Insidious, prolonged

Valvular damage

Frequently severe

Usually less destructive

Repair response

Limited in rapidly destructive foci

Granulation and organization may occur

Slide 12 · Valvular risk factors have changed

Rheumatic valve scarring was historically the major substrate.

As rheumatic disease declined, other structural lesions became prominent.

Modern substrate includes degenerative disease, congenital anomalies and prostheses.

Previous valve injury is common—but is not required for IE.

Slide 13 · Predisposing cardiac abnormalities

Rheumatic scarring

A previously damaged valve provides susceptible tissue.

Mitral valve prolapse

One of the important contemporary structural substrates.

Calcific stenosis

Degenerative calcification is an antecedent valve lesion.

Bicuspid aortic valve

Susceptibility may occur with or without calcification.

Congenital defects

Altered cardiac structure increases risk.

Prosthetic valves

An implanted valve is a distinct infection substrate.

Slide 14 · Pre-existing damage is not obligatory

A previously abnormal valve can favor certain infections.

Highly virulent microorganisms can invade apparently normal valves.

S. Aureus exemplifies infection in either normal or deformed valves.

Evaluate microbial virulence and the cardiac substrate together.

Slide 15 · Microbiology follows ecological reservoirs

Oral flora

Viridans streptococci and HACEK organisms.

Skin flora

Staphylococcus aureus; S. Epidermidis in early prosthetic infection.

Other agents

Enterococci, gram-negative bacilli and fungi.

Slide 16 · Viridans streptococci: Damaged native valves

Members of normal oral flora.

Especially important in IE of native valves that were previously abnormal.

50%–60% in that specific substrate category.

A prototypic cause of subacute IE.

Slide 17 · Staphylococcus aureus: Virulent infection

Skin-associated organism with substantial invasive potential.

Can infect valves that are healthy or already deformed.

The major offender described in injection-associated IE.

Associated with acute, tissue-destructive disease.

Slide 18 · Injection drug use changes the risk profile

Contaminated needles can directly introduce organisms into blood.

S. Aureus is particularly important in this clinical setting.

Right-sided valves may be infected.

Valve location, exposure and organism offer mutually supporting clues.

Slide 19 · HACEK organisms and other bacterial causes

HACEK: Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella.

This group as oral-cavity commensals.

Enterococci are another recognized cause of IE.

Gram-negative bacilli beyond HACEK are less common.

Slide 20 · Fungal infective endocarditis

Bacterial organisms account for most IE.

Fungal infection is an established, less frequent alternative.

The pathology remains an infected vegetation with destructive potential.

Identification of the infecting organism is central to management.

Slide 21 · Prosthetic valve infection: Timing and agents

Soon after implantation

Roughly 1–2 months after valve surgery

Skin-associated S. Aureus and S. Epidermidis predominate

Implantation creates a distinct infection setting

Late after implantation

At least 1 year after surgery discussion

Streptococci and S. Aureus are prominent

Late infection differs from the perioperative pattern

Slide 22 · Culture-negative endocarditis

The textbook estimates approximately 10% of IE as culture-negative.

Antibiotics given before cultures can suppress growth.

Some causative organisms are difficult to recover.

Organisms embedded in a vegetation may enter blood intermittently.

Slide 23 · Bloodstream entry precedes valvular seeding

Infected focus or barrier breach

Bacteremia or fungemia

Organisms reach cardiac endocardium

Infected vegetations develop

Potential entries: Oral cavity, gut, skin, procedures and contaminated injection equipment.

Slide 24 · Potential sources of bloodstream seeding

Overt infection at another anatomic site.

Dental or surgical procedure-associated bloodstream exposure.

Contaminated needles in injection drug use.

Minor epithelial-barrier breaks in oral, gastrointestinal or cutaneous sites.

Slide 25 · Two risk domains must be considered

Microbial exposure: Organisms must enter the bloodstream.

Cardiac susceptibility: Structural disease often increases risk.

A sufficiently virulent organism may infect an intact valve.

Absence of known heart disease does not exclude IE.

Slide 26 · Three mechanistic consequences of vegetation formation

Persistent infection

Organisms remain within fibrin-rich infected material.

Mechanical disruption

Bulky lesions and invasion can impair leaflet function.

Embolic shedding

Friable fragments break away into the circulation.

Slide 27 · The term “vegetation” needs qualification

A vegetation is a mass on a valvular/endocardial surface.

In IE it contains organisms and an inflammatory component.

Noninfected vegetations also occur in other diseases.

Morphology, microbiology and clinical context establish the distinction.

Slide 28 · Gross hallmark: A bulky, friable vegetation

Friable infected vegetation

Valve leaflet

Interpretation

Irregular mass on the valve surface.

Fibrin, inflammation and organisms are present.

The lesion may erode or destroy underlying tissue.

Slide 29 · Aortic and mitral valve predominance

These are the commonest sites account.

One or several vegetations can occur on a leaflet.

More than one valve may be infected.

Morphologic location must be interpreted with clinical exposure.

Slide 30 · Why vegetation friability matters

Friable infected vegetation

Valve leaflet

Interpretation

Loose infected fragments can detach.

Embolic fragments may seed infection distally.

Septic infarcts and abscesses may follow.

Slide 31 · Vegetation to septic embolus

Friable infected mass

Fragment detaches

Bloodstream carries infected embolus

Septic infarct / abscess

The infected character of the embolic fragment changes its downstream consequences.

Slide 32 · Valvular injury: More than surface thrombus

IE may erode valve cusps and adjoining tissue.

Destruction can create a new valvular defect.

The resultant turbulent flow or regurgitation may generate a murmur.

Tissue invasion differentiates destructive IE from bland sterile deposits.

Slide 33 · How a ring abscess develops

Infected valve vegetation

Spread beneath/around valve

Perivalvular tissue destruction

Ring (annular) abscess

Ring abscess with acute S. Aureus infection of a bicuspid aortic valve.

Slide 34 · Perivalvular infection is a high-risk feature

Extension can invade the underlying myocardium.

Annular (“ring”) abscess is a characteristic severe lesion.

Arrhythmia may suggest spread into myocardium/conduction structures.

Local anatomic destruction may prompt surgical intervention.

Slide 35 · The basic microscopic constituents

Fibrin is a major structural component of the vegetation.

Inflammatory cells are admixed with infected material.

Bacteria or other causative organisms may be embedded.

The histologic diagnosis depends on infection-related findings in context.

Slide 36 · Subacute vegetation may show organization

Chronic infected vegetation

Granulation tissue at the base

Healing response and remodeling

Fibrosis ± calcification

Chronic inflammatory cells can accompany the later organization of subacute lesions.

Slide 37 · Acute and subacute morphology can overlap

Acute vegetations are often more destructive.

Subacute lesions tend to preserve more valve substance.

Granulation tissue favors an evolving healing response.

A single histologic feature cannot rigidly define clinical tempo.

Slide 38 · Infected versus sterile vegetation

Friable infected vegetation

Valve leaflet

Interpretation

IE vegetation is bulky, friable and infected.

A sterile thrombus need not destroy the valve.

Gross appearance alone is not sufficient for final classification.

Slide 39 · Rheumatic endocarditis: Closure-line verrucae

Small verrucae at closure line

Interpretation

Small, warty lesions follow the line of closure.

They occur during the rheumatic fever phase.

Distribution and size differ from typical bulky IE.

Slide 40 · Nonbacterial thrombotic endocarditis

Small, bland, non-destructive thrombi

Interpretation

Typical sterile vegetations are small and bland.

Usually located along the line of valve closure.

Their local effect is generally nondestructive.

Slide 41 · NBTE: Histology and embolic hazard

Sterile thrombi measure approximately 1–5 mm.

Vegetations are bland and loosely attached.

They elicit little or no inflammatory reaction.

Embolization can cause major infarcts despite minimal valve injury.

Slide 42 · NBTE: Hypercoagulable substrate

Occurs in debilitated states, including malignancy or sepsis.

Associated with chronic disseminated intravascular coagulation.

Mucinous adenocarcinomas can generate a procoagulant milieu.

Damaged valves are not a prerequisite.

Slide 43 · Libman–Sacks vegetations: Distinct distribution

Vegetations on either leaflet surface

Interpretation

Sterile small-to-medium lesions in systemic lupus.

Can occur on either or both valve surfaces.

May extend to chordae or chamber endocardium.

Slide 44 · Libman–Sacks: Immune-mediated valvulitis

Immune-complex deposition activates complement.

Fc-receptor–bearing inflammatory cells are recruited.

Valvulitis and fibrinoid necrosis are characteristic.

Persistent injury can cause scarring and leaflet fusion.

Slide 45 · Four vegetative patterns: Key discriminators

Pattern

Infection?

Typical distribution

Principal tissue effect

Infective

Yes

Bulky irregular mass; may extend to chordae

Potential tissue destruction

Rheumatic

No infection in verrucae

Small closure-line warts

Rheumatic valvulitis/scarring

NBTE

Sterile

Small closure-line thrombi

Minimal local reaction; emboli possible

Libman–Sacks

Sterile

Either or both valve surfaces

Valvulitis, fibrinoid necrosis

Slide 46 · Acute presentation is often systemic

Fever may develop rapidly with chills.

Weakness and lassitude accompany the febrile illness.

A fulminant course should raise concern for virulent infection.

The pattern reflects systemic infection plus cardiac involvement.

Slide 47 · Older patients may have muted findings

Fever is the most consistent sign but may be low-grade or absent.

Fatigue and weight loss may dominate.

A nonspecific “flu-like” illness can obscure diagnosis.

Absence of a dramatic fever does not exclude IE.

Slide 48 · How a murmur can arise in IE

Vegetation and valve injury

Altered leaflet coaptation

Abnormal flow / regurgitation

Audible cardiac murmur

Some murmurs predate infection because structural disease was already present.

Slide 49 · A murmur is useful but not absolute

Most patients with left-sided IE have a murmur.

Some murmurs reflect new valve injury.

Others arise from a pre-existing valve abnormality.

Murmur interpretation requires previous cardiac history.

Slide 50 · Three clinical consequence domains

Cardiac

Valve damage, ring abscess and arrhythmia.

Embolic/infectious

Septic emboli, distant abscesses and sepsis.

Immune-mediated

Immune-complex glomerulonephritis.

Slide 51 · Classical peripheral signs: Now less frequent

Improved diagnosis and treatment reduced prolonged untreated disease.

Splinter hemorrhages may reflect microembolic events.

Janeway lesions involve palms or soles.

Osler nodes and Roth spots are other historical diagnostic clues.

Slide 52 · Janeway lesions: Vascular phenomenon

Typically erythematous or hemorrhagic lesions.

Nontender macules on palms or soles.

The textbook associates these with septic embolic events.

Duke criteria list them among vascular phenomena.

Slide 53 · Osler nodes and Roth spots: Immune clues

Osler nodes are tender nodules, usually at finger pulp.

Roth spots are retinal hemorrhages with pale centers.

These are listed among Duke immunologic phenomena.

Do not assume their absence excludes IE.

Slide 54 · Splinter hemorrhages: Contextual clue

Linear subungual hemorrhages can accompany microembolic disease.

Historically associated with long-standing IE.

They are not specific on their own.

Interpret peripheral signs alongside cultures and cardiac findings.

Slide 55 · Diagnosis integrates independent evidence

Clinical suspicion

Microbiologic evidence

Cardiac imaging ± direct assessment

Duke-ISCVID classification

Source table: 2023 Duke-ISCVID criteria, reproduced 11e.

Slide 56 · Pathologic diagnosis: Organism in relevant tissue

Demonstration may be by culture or histologic examination.

Relevant material includes valve vegetation or an embolized fragment.

Explanted prosthetic valves/sewing rings and device material also qualify.

Pathologic evidence is distinct from clinical criteria.

Slide 57 · Clinical Duke categories: Source table

Clinical diagnostic combinations: 2 major criteria; Or

1 major plus 3 minor criteria; Or

5 minor criteria.

These are the positive combinations printed Table 12.9.

Slide 58 · Major microbiologic criteria

Characteristic organisms identified by blood culture.

Nucleic acid–based assays or immunofluorescence may contribute.

Persistently positive results for unusual organisms also feature.

Exact microbial interpretation depends on the criterion wording.

Slide 59 · Major imaging and operative criteria

Imaging can demonstrate a valve- or implant-related oscillating mass.

Abscess or partial separation of an artificial valve are major findings.

New valve regurgitation detected by imaging is included.

Direct inspection during cardiac surgery can provide a major criterion.

Slide 60 · Duke minor criteria: Host context and fever

A predisposition can be heart lesion, prosthetic valve or intracardiac device.

Injection drug use is an additional predisposing context.

Fever is a minor clinical criterion.

Risk factors support interpretation; They do not independently prove IE.

Slide 61 · Duke minor criteria: Vascular phenomena

Major arterial embolism or septic pulmonary infarct.

Mycotic aneurysm or intracranial hemorrhage.

Conjunctival hemorrhages and Janeway lesions.

These link cardiac infection to vascular consequences.

Slide 62 · Duke minor criteria: Immune and laboratory findings

Immune findings: Glomerulonephritis, Osler nodes, Roth spots.

Rheumatoid factor is included as an immune phenomenon.

A single culture positive for an unusual organism may count as minor microbiologic evidence.

Categories should not be double-counted as independent major findings.

Slide 63 · Three diagnostic evidence streams

Cultures / assays

Identify the microorganism and establish microbiologic evidence.

Cardiac imaging

Detect vegetations, abscess, dehiscence and new regurgitation.

Clinical context

Assess fever, substrate, vascular events and immune phenomena.

Slide 64 · Systemic consequences of left-sided IE

Infected left-sided vegetation

Systemic arterial embolization

Distal tissue ischemia + bacterial seeding

Septic infarct / abscess

The destination organ depends on the vascular distribution of the embolus.

Slide 65 · Septic infarcts and mycotic aneurysms

Embolic material may contain viable organisms.

Secondary infection can form an abscess at the embolization site.

An infected vessel wall can develop a mycotic aneurysm.

“Mycotic” in this context does not necessarily mean fungal.

Slide 66 · Immune-complex glomerulonephritis

Persistent IE antigenemia

Antigen–antibody complexes

Glomerular deposition

Inflammatory renal injury

This is immune-mediated injury, distinct from a septic renal embolus.

Slide 67 · Cardiac invasion can disturb conduction

Annular infection may extend into myocardial tissue.

Conduction structures may be involved by adjacent inflammation.

New arrhythmias can be a warning sign of extension.

An arrhythmia does not specify the lesion, but raises concern.

Slide 68 · Adverse features in the clinical course

Sepsis indicates serious systemic infection.

Arrhythmia may reflect local myocardial/conduction invasion.

Systemic embolization can produce organ injury.

These features are described as especially unfavorable.

Slide 69 · Principles of treatment and prognosis

Untreated IE is usually fatal.

Prolonged effective antimicrobial therapy is central.

Valve replacement may be necessary for destructive disease.

Prosthetic-valve IE has particularly challenging outcomes.

Slide 70 · Case application: Acute destructive IE

Clinical vignette

Acute fever and chills; New murmur.

No documented prior valve disease.

Blood cultures grow Staphylococcus aureus.

Cardiac imaging demonstrates a destructive vegetation.

Question: Which features point toward the acute pattern?

Slide 71 · Case reasoning: Acute destructive pattern

Rapid onset supports the acute clinical tempo.

S. Aureus can invade previously normal valves.

Destructive valvular morphology strengthens the pattern.

Major microbiology and imaging findings also support the IE diagnosis.

Slide 72 · Case application: Persistent febrile illness

Clinical vignette

Weeks of fatigue and intermittent low-grade fever.

A pre-existing structurally abnormal valve.

Blood cultures identify viridans streptococci.

Imaging reveals a valve vegetation.

Question: Why is a subacute pattern more plausible?

Slide 73 · Case reasoning: Subacute infection

Prolonged, insidious symptoms favor the subacute spectrum.

The damaged native valve is a typical substrate.

Viridans organisms are a textbook etiologic example.

Subacute morphology may show organization at the lesion base.

Slide 74 · Case application: Vegetation without infection

Pathology vignette

An individual with mucinous adenocarcinoma develops emboli.

Valve shows small, bland, sterile thrombi at the closure line.

No destructive valvulitis is identified.

Question: Which noninfected form best fits?

Slide 75 · Case reasoning: Nonbacterial thrombotic endocarditis

Hypercoagulability in malignancy favors NBTE.

Small closure-line sterile thrombi are the typical morphology.

Major systemic emboli may occur without valve destruction.

Do not mistake sterile vegetation for infective endocarditis.

Slide 76 · Integrated synthesis: Three decisive questions

Is the lesion infected or sterile?

How virulent is the organism, and what valve substrate exists?

Is there local destruction, septic embolization or immune injury?

Do microbiology and cardiac imaging support the clinical diagnosis?

Slide 77 · References and source limitations

Robbins, Cotran & Kumar: Pathologic Basis of Disease, 11th ed. (2026), ch. 12, pp. 511–514.

Diagnostic clinical criteria: Robbins Table 12.9, adapted from the 2023 Duke-ISCVID criteria (Fowler et al., Clin Infect Dis. 2023;77:518–526).

All valve drawings and flow diagrams are original, editable explanatory schematics—not photographs of pathology specimens.

Original textbook figure images and chapter PDF were not provided; figure-specific visual verification was therefore not performed.