Infective Endocarditis (IE)

A 45-year-old man presents to the emergency department with a 1-week history of fever, chills, pleuritic chest pain, and shortness of breath. He reports fatigue and decreased appetite. His medical history is significant for intravenous drug use. On examination, his temperature is 39°C, pulse is 110/min, and blood pressure is 100/60 mm Hg. Cardiac auscultation reveals a holosystolic murmur best heard at the left lower sternal border that increases with inspiration. Multiple painless erythematous lesions on the palms and linear hemorrhages under the fingernails are noted. Laboratory studies show leukocytosis. Blood cultures grow Staphylococcus aureus. Chest imaging demonstrates multiple nodular infiltrates consistent with septic pulmonary emboli. Transesophageal echocardiography reveals a mobile vegetation on the tricuspid valve. Diagnosis?

Diagnosis is acute right-sided infective endocarditis, complicated by septic pulmonary emboli.

1. Definition

Infective endocarditis is a microbial infection of the endocardial surface, most commonly affecting the cardiac valves, characterized by vegetations composed of fibrin, platelets, and microorganisms, leading to valvular destruction and systemic embolization.

2. Epidemiology and Risk Factors

2.1 Epidemiology

1. Incidence increasing due to prosthetic valves, cardiac devices, and aging population
2. Mortality remains high (15–30%) despite treatment
3. Left-sided IE more common overall; right-sided IE common in IVDU

2.2 Risk Factors

Structural Cardiac Abnormalities

1. Prosthetic valves (highest risk)
2. Congenital heart disease (especially cyanotic)
3. Degenerative valvular disease
4. Prior infective endocarditis

Exposure-Related Risks

1. Intravenous drug use
2. Poor dentition / dental procedures
3. Indwelling vascular catheters
4. Cardiac implantable devices (pacemakers, ICDs)

Host Factors

1. Age >60 years
2. Diabetes mellitus
3. Immunosuppression
4. Chronic kidney disease / hemodialysis

Clinical heuristic: Endothelial injury + bacteremia + time → IE

3. Pathophysiology

3.1 Core Mechanism

1. Endothelial injury → turbulent flow or prosthetic surface
2. Formation of NBTE (platelet-fibrin nidus)
3. Transient bacteremia (oral, skin, GI/GU)
4. Microbial adhesion (adhesins, biofilm formation)
5. Formation of infected vegetations
6. Continuous bacteremia + immune activation

3.2 Key Pathological Features

1. Vegetations are avascular → poor antibiotic penetration
2. Biofilm formation (prosthetic valves) → antibiotic resistance
3. Valve destruction → regurgitation and heart failure

3.3 Systemic Effects

1. Septic emboli → infarcts (brain, spleen, kidney, lungs)
2. Immune complex deposition → glomerulonephritis, Osler nodes, Roth spots
3. Mycotic aneurysm formation

3.4 Special Forms

1. Marantic (NBTE) → malignancy, hypercoagulable states
2. Libman–Sacks endocarditis → SLE (sterile vegetations)

4. Microbiology

4.1 Common Organisms

1. Staphylococcus aureus → most common overall, acute IE
2. Viridans streptococci → subacute IE (oral source)
3. Enterococcus faecalis → GI/GU source
4. Coagulase-negative staphylococci → prosthetic valves

4.2 Special Situations

1. IVDU → S. aureus, ± Pseudomonas, Candida
2. Prosthetic valve IE → S. epidermidis, biofilm producers
3. Healthcare-associated IE → MRSA

4.3 Culture-Negative IE

1. Prior antibiotic exposure (most common)
2. Fastidious organisms:
• HACEK group
• Coxiella burnetii (Q fever)
• Bartonella spp.
3. Fungal IE

Important association: Streptococcus gallolyticus → colorectal cancer

4.4 Virulence Concept

1. High virulence (S. aureus) → infects normal valves, rapid destruction
2. Low virulence (Viridans) → requires pre-damaged valve

5. Clinical Features

5.1 Core Triad (often absent)

1. Fever
2. New valvular regurgitation murmur
3. Embolic or immunologic phenomena

5.2 Mechanism-Based Features

1. Infection

• Fever, malaise, weight loss

2. Cardiac Involvement

1. New regurgitant murmur (hallmark)
2. Heart failure (most serious complication)
3. Conduction abnormalities → periannular abscess

3. Embolic Phenomena

1. Left-sided IE → systemic emboli:
• Stroke
• Renal infarct
• Splenic infarct
2. Right-sided IE → septic pulmonary emboli:
• Dyspnea
• Pleuritic chest pain
• Hemoptysis

4. Immune-Mediated

1. Osler nodes (painful)
2. Roth spots
3. Glomerulonephritis

5. Vascular Phenomena

1. Janeway lesions (painless)
2. Splinter hemorrhages

Memory anchor: Janeway = painless (septic) | Osler = painful (immune)

5.3 Special Populations

1. Elderly → subtle, afebrile
2. IVDU → right-sided IE with pulmonary findings

6. Diagnostic Evaluation

6.1 Blood Cultures

1. Obtain 3 sets from separate sites
2. Draw before antibiotics
3. Do not delay antibiotics in unstable patients
4. Repeat until clearance of bacteremia

6.2 Echocardiography

1. TTE → initial
2. TEE (gold standard) → detects:
• Vegetations
• Abscess
• Prosthetic valve involvement

6.3 Diagnostic Criteria (Modified Duke Framework)

Major

1. Positive blood cultures
2. Echo evidence or new regurgitation

Minor

1. Fever
2. Predisposition
3. Vascular phenomena
4. Immunologic phenomena

6.4 Additional Imaging

1. CT/MRI → emboli, abscess
2. PET/CT → prosthetic/device infection

Diagnostic Pitfalls

1. Prior antibiotics → culture-negative IE
2. Negative TTE ≠ exclude IE → perform TEE

7. Key Clinical Insight

Persistent bacteremia + new valvular regurgitation + systemic manifestations = infective endocarditis

8. Management

8.1 Initial Stabilization

1. Assess hemodynamics
2. Provide oxygen
3. Establish IV access
4. Manage sepsis (fluids ± vasopressors)

8.2 Empiric Antibiotic Therapy

1. Start empiric IV bactericidal therapy after cultures
2. Choice depends on:
• Native vs prosthetic valve
• Community vs healthcare-associated
• Local resistance patterns

8.3 Targeted Therapy

1. Use culture-directed bactericidal antibiotics
2. Duration: 4–6 weeks IV

Key regimens:

• MSSA → nafcillin/oxacillin
• MRSA → vancomycin/daptomycin
• Viridans streptococci → penicillin/ceftriaxone
• Enterococcus → ampicillin + ceftriaxone

8.4 Monitoring

1. Repeat blood cultures
2. Persistent bacteremia → treatment failure
3. Monitor for:
• Heart failure
• Abscess
• Embolic events

8.5 Indications for Surgery

Absolute

1. Heart failure
2. Periannular abscess
3. Persistent bacteremia ≥5–7 days
4. Fungal/resistant organism

Relative

1. Vegetation >10 mm
2. Recurrent emboli

Right-Sided IE

1. Vegetation >20 mm + recurrent pulmonary emboli
2. Severe tricuspid regurgitation with heart failure

Clinical heuristic: HF + uncontrolled infection + embolic risk → surgery

8.6 Prevention

1. Remove source of bacteremia
2. Counsel for IVDU cessation
3. Maintain oral hygiene

9. Prophylaxis

Indications

1. Prosthetic valves
2. Prior IE
3. Cyanotic CHD (unrepaired or residual defect)
4. Cardiac transplant with valvular disease

Regimen

• Amoxicillin 2 g orally 30–60 min before dental procedure

Important: Routine prophylaxis NOT recommended

10. Complications

Cardiac

1. Heart failure
2. Valve destruction
3. Abscess → conduction block

Embolic

1. Stroke
2. Pulmonary emboli
3. Splenic infarction

Infectious

1. Persistent bacteremia
2. Mycotic aneurysm

11. Prognosis

Worse with:

1. Staphylococcus aureus
2. Prosthetic valves
3. Heart failure
4. Large vegetations
5. Delayed treatment

12. Exam-Level Pearls

1. Most common organism → Staphylococcus aureus
2. TEE > TTE
3. New regurgitation = key finding
4. Persistent bacteremia → surgery
5. Right-sided IE → pulmonary emboli
6. Osler (painful) vs Janeway (painless)
7. Strep gallolyticus → colon cancer

Aortic Stenosis

A 72 year old male presents with progressive exertional dyspnea, episodes of chest pain, and a recent episode of syncope while climbing stairs. He has a history of hypertension and hyperlipidemia. On examination, his pulse is low amplitude and delayed. Blood pressure is 130/85 mm Hg. Cardiac auscultation reveals a harsh crescendo–decrescendo systolic ejection murmur best heard at the right upper sternal border, radiating to the carotids. The second heart sound is soft, and an S4 gallop is present. Echocardiography shows aortic valve area of 0.8 cm², peak velocity of 4.5 m/s, and mean gradient of 50 mmHg, with preserved LVEF. Diagnosis?

Diagnosis is Symptomatic Severe Aortic Stenosis.

1. Definition

Aortic stenosis is a valvular disorder characterized by progressive narrowing of the aortic valve, resulting in obstruction to left ventricular outflow, causing pressure overload, concentric left ventricular hypertrophy, and eventual heart failure.

2. Etiology

1. Degenerative calcific AS (most common in elderly)
• Progressive leaflet calcification and reduced mobility
• Risk factors overlap with atherosclerosis
2. Bicuspid aortic valve
• Congenital abnormality leading to early calcification
• Presents earlier, often in middle age
3. Rheumatic heart disease
• Commissural fusion, often with concomitant mitral disease

3. Pathophysiology

1. Fixed obstruction increases afterload → concentric LV hypertrophy
2. LVH leads to:
• Increased oxygen demand
• Reduced subendocardial perfusion
3. Results in myocardial ischemia even without CAD
4. Diastolic dysfunction develops due to stiff ventricle
5. Advanced disease leads to:
• Reduced stroke volume
• Decreased cardiac output
• Pulmonary congestion and heart failure

4. Clinical Features

4.1 Classic Triad

1. Angina
• Due to supply-demand mismatch
2. Dyspnea
• Due to elevated LV filling pressures
3. Syncope (exertional)
• Due to inability to augment cardiac output during vasodilation

4.2 Additional Features

1. Fatigue and reduced exercise tolerance
2. Presyncope or dizziness
3. Signs of heart failure in advanced disease

5. Special Association

Heyde Syndrome

1. Aortic stenosis + GI bleeding from angiodysplasia
2. Mechanism:
• High shear stress across valve → degradation of von Willebrand factor
• Leads to acquired bleeding tendency

6. Physical Examination

1. Murmur
• Harsh crescendo–decrescendo systolic murmur
• Best heard at right upper sternal border
• Radiates to carotids
• May radiate to apex
2. Carotid pulse
• Pulsus parvus et tardus
3. Heart sounds
• Soft or absent A2
• Paradoxical splitting of S2
• S4 gallop
4. Pulse pressure
• Often narrow
5. Dynamic maneuvers
• Increases with squatting
• Decreases with Valsalva

7. Diagnosis

7.1 Transthoracic Echocardiography (Gold Standard)

Evaluates:

1. Valve anatomy and calcification
2. Aortic valve area (AVA)
3. Peak velocity
4. Mean gradient
5. Left ventricular function

Severity must be assessed using multiple parameters.

7.2 Additional Investigations

1. ECG
• LVH, left atrial enlargement
2. Chest X-ray
• LV enlargement
• Aortic valve calcification
• Post-stenotic dilation
3. Cardiac catheterization
• Used when noninvasive data are discordant
• Required before intervention

8. Severity Classification

Severity	AVA (cm²)	Velocity (m/s)	Gradient (mmHg)
Mild	>1.5	<3	<20
Moderate	1.0–1.5	3–4	20–40
Severe	≤1.0	≥4	≥40

9. Hemodynamic Subtypes

9.1 Classical Low-Flow Low-Gradient

• LVEF <50%
• Reduced stroke volume
• Requires dobutamine stress echo

9.2 Paradoxical Low-Flow Low-Gradient

• LVEF ≥50%
• Small, stiff LV
• Reduced stroke volume

9.3 Normal-Flow Low-Gradient

• Discordant findings
• Requires careful reassessment

10. Management

10.1 Medical Therapy

1. Symptomatic relief only
2. Diuretics for congestion, used cautiously
3. Treat hypertension carefully, including ACE inhibitors or ARBs
4. Maintain adequate preload

Medical therapy does not halt disease progression.

10.2 Definitive Treatment

Valve replacement is the only curative therapy

SAVR

• Preferred in younger patients
• Bicuspid valve
• Concomitant surgery needed

TAVR

• Preferred in older patients or high-risk individuals
• Decision based on age, anatomy, and comorbidities

11. Indications for Valve Replacement

1. Symptomatic severe AS
2. Severe AS with LVEF <50%
3. Selected asymptomatic patients with:
• Very severe AS
• Abnormal exercise test
• Rapid progression
• Elevated BNP

12. Complications

1. Heart failure
2. Arrhythmias
3. Sudden cardiac death
4. Pulmonary hypertension

13. Prognosis

1. Long asymptomatic phase
2. Once symptoms develop:
• Angina → ~5 year survival
• Syncope → ~3 year survival
• Heart failure → ~2 year survival

14. Key Clinical Insight

Aortic stenosis should be suspected in elderly patients with exertional syncope, angina, or dyspnea and a systolic murmur radiating to the carotids

Triad of angina, syncope, and dyspnea = symptomatic severe aortic stenosis → urgent valve replacement

15. Exam Pearls

1. Triad: angina, syncope, dyspnea
2. Murmur radiates to carotids
3. Pulsus parvus et tardus is hallmark
4. Echo is diagnostic
5. Low-flow low-gradient AS requires careful evaluation
6. Valve replacement is definitive treatment
7. Do not delay intervention once symptoms appear

Kounis Syndrome

A 25 year old male develops acute onset chest pain, shortness of breath, and generalized urticaria shortly after receiving intravenous atropine for symptomatic bradycardia. He also reports palpitations, vomiting, and diaphoresis. On examination, he appears pale and diaphoretic, with diffuse wheezing on lung auscultation and generalized urticaria. Oxygen saturation is reduced. Electrocardiography shows ST-segment elevation in the inferolateral leads with reciprocal changes. Cardiac troponins may be mildly elevated. Emergency coronary angiography reveals normal coronary arteries, and echocardiography is normal with no regional wall motion abnormalities, consistent with transient coronary vasospasm. Symptoms and ECG changes resolve rapidly after treatment with corticosteroids, antihistamines, and supportive care. Diagnosis?

Diagnosis is Type I Kounis Syndrome triggered by atropine.

1. Definition

Kounis syndrome is an acute coronary syndrome triggered by an allergic or hypersensitivity reaction, resulting in coronary vasospasm, plaque rupture, or stent thrombosis.

2. Pathophysiology

1. Allergen exposure activates mast cells, basophils, and inflammatory pathways
2. Release of mediators such as histamine, leukotrienes, and platelet-activating factor
3. These mediators cause:
1. Coronary vasospasm
2. Plaque rupture in patients with underlying coronary artery disease
3. Stent thrombosis in previously stented patients

3. Classification

1. Type I
• Occurs in patients with normal coronary arteries
• Causes coronary vasospasm
• Troponin may be normal or mildly elevated
2. Type II
• Occurs in patients with pre-existing atherosclerotic disease
• Leads to plaque rupture and acute myocardial infarction
3. Type III
• Occurs in patients with coronary stents
• Leads to stent thrombosis

4. Clinical Features

4.1 Cardiac Features

1. Chest pain
2. Dyspnea
3. Palpitations
4. Nausea and vomiting

4.2 Allergic Features

1. Urticaria
2. Rash
3. Wheezing
4. Angioedema
5. Hypotension or anaphylaxis

5. Diagnosis

1. Clinical suspicion is key
• Acute coronary syndrome symptoms plus allergic manifestations
2. Electrocardiography
• ST elevation or depression
• Changes may be transient in Type I
3. Cardiac biomarkers
• Troponin may be normal or mildly elevated
4. Coronary angiography
• Normal coronaries in Type I
• Abnormal findings in Type II and III
5. Allergy markers
• Serum tryptase or IgE may support diagnosis

6. Key Clinical Insight

Chest pain with ECG changes in the presence of allergic features strongly suggests Kounis syndrome rather than primary acute coronary syndrome

7. Management

7.1 Core Principle

Simultaneously treat the allergic reaction and myocardial ischemia.

7.2 Allergic Component

1. Corticosteroids
2. Antihistamines (H1 and H2 blockers)
3. Oxygen therapy and intravenous fluids if required

7.3 Cardiac Component

Type I

1. Primary treatment is control of the allergic reaction
2. Nitrates or calcium channel blockers may be used for vasospasm if hemodynamically stable

Type II and III

1. Manage as acute coronary syndrome
2. Add steroids and antihistamines

7.4 Important Drug Considerations

1. Epinephrine
• Remains first line for life-threatening anaphylaxis
• Use with caution due to risk of worsening coronary vasospasm
2. Beta blockers
• Avoid in the acute phase due to risk of unopposed alpha-mediated vasoconstriction
3. Morphine
• Avoid due to histamine release and potential worsening of vasospasm

8. Prognosis

1. Type I generally has a favorable prognosis with prompt treatment
2. Type II and III depend on severity of underlying coronary disease
3. Early recognition reduces risk of myocardial infarction, arrhythmias, and death

9. Exam Level Pearls

1. Kounis syndrome = allergic reaction + acute coronary syndrome
2. Suspect when ACS symptoms occur with urticaria, wheeze, or anaphylaxis
3. Normal coronary angiography with ST elevation suggests Type I
4. Avoid beta blockers and morphine in acute phase
5. Use epinephrine cautiously but do not withhold in severe anaphylaxis
6. ECG changes often resolve after treatment of the allergic reaction