1. Atherosclerosis / Arteriosclerosis
   • Pathogenesis, risk factors, fatty streak, Monckeberg sclerosis, complications
2. Aneurysms
   • Definition, types, and detailed discussion of one type
3. Congenital heart disease
   • Tetralogy of Fallot
4. Ischaemic heart disease / Myocardial infarction
   • Acute MI case diagnosis, investigations, pathogenesis, morphology, biomarkers, complications, clinical features
5. Acute rheumatic fever / Rheumatic heart disease
   • Clinical case, pathogenesis, Aschoff bodies/nodules, MacCallum plaques
6. Infective endocarditis / Valvular disease
   • Case diagnosis, classification with organisms, cardiac changes, vegetations

1. Arteriosclerosis and atherosclerosis
   • Pathogenesis, risk factors, morphology, fatty streak, Monckeberg medial sclerosis, complications.
2. Aneurysms
   • Definition, classification, and a detailed answer on an important type, usually aortic aneurysm or aortic dissection.
3. Congenital heart disease
   • Tetralogy of Fallot: components, pathogenesis, morphology, clinical features, complications.
4. Ischaemic heart disease and acute myocardial infarction
   • Acute MI case, diagnosis, investigations, pathogenesis, sequential gross and microscopic changes, cardiac biomarkers, complications.
5. Acute rheumatic fever and rheumatic heart disease
   • Clinical case, diagnostic basis, pathogenesis, cardiac lesions, Aschoff bodies, MacCallum plaques, investigations.
6. Infective endocarditis and valvular disease
   • Clinical case, diagnosis, etiologic classification, morphology of vegetations, complications, and distinction from nonbacterial vegetations.

1. Atherosclerosis / Arteriosclerosis
   • Pathogenesis, risk factors, fatty streak, Monckeberg sclerosis, complications
2. Aneurysms
   • Definition, types, and detailed discussion of one type
3. Congenital heart disease
   • Tetralogy of Fallot
4. Ischaemic heart disease / Myocardial infarction
   • Acute MI case diagnosis, investigations, pathogenesis, morphology, biomarkers, complications, clinical features
5. Acute rheumatic fever / Rheumatic heart disease
   • Clinical case, pathogenesis, Aschoff bodies/nodules, MacCallum plaques
6. Infective endocarditis / Valvular disease
   • Case diagnosis, classification with organisms, cardiac changes, vegetations

1. Arteriosclerosis and atherosclerosis
   • Pathogenesis, risk factors, morphology, fatty streak, Monckeberg medial sclerosis, complications.
2. Aneurysms
   • Definition, classification, and a detailed answer on an important type, usually aortic aneurysm or aortic dissection.
3. Congenital heart disease
   • Tetralogy of Fallot: components, pathogenesis, morphology, clinical features, complications.
4. Ischaemic heart disease and acute myocardial infarction
   • Acute MI case, diagnosis, investigations, pathogenesis, sequential gross and microscopic changes, cardiac biomarkers, complications.
5. Acute rheumatic fever and rheumatic heart disease
   • Clinical case, diagnostic basis, pathogenesis, cardiac lesions, Aschoff bodies, MacCallum plaques, investigations.
6. Infective endocarditis and valvular disease
   • Clinical case, diagnosis, etiologic classification, morphology of vegetations, complications, and distinction from nonbacterial vegetations.

1. Atherosclerosis
   • Definition, risk factors, response-to-injury pathogenesis, morphology, complications.
2. Aneurysm
   • Definition, classification, and detailed account of abdominal aortic aneurysm or aortic dissection.
3. Tetralogy of Fallot
   • Four components, developmental basis, morphology, clinical features, complications.
4. Acute myocardial infarction
   • Case diagnosis and investigations; pathogenesis; time-wise gross and microscopic changes; biomarkers; complications.
5. Acute rheumatic fever with rheumatic heart disease
   • Clinical diagnosis, evidence of preceding streptococcal infection, immune pathogenesis, cardiac pathology, investigations.
6. Infective endocarditis
   • Case diagnosis, classification with organisms, pathogenesis, morphology of vegetations, complications, and differential diagnoses.

1. Atherosclerosis

Definition

Risk factors

Non-modifiable

1. Increasing age
2. Male sex. Risk rises in women after menopause.
3. Family history and genetic predisposition
4. Genetic lipid disorders, for example familial hypercholesterolaemia

Major modifiable

1. Hyperlipidaemia, especially raised LDL cholesterol and reduced HDL cholesterol
2. Hypertension
3. Cigarette smoking
4. Diabetes mellitus

Other factors

• Obesity and sedentary lifestyle
• Atherogenic diet
• Metabolic syndrome
• Chronic inflammation, for example increased CRP
• Hyperhomocysteinaemia
• Lipoprotein(a) elevation

Pathogenesis: response-to-endothelial-injury hypothesis

Sequence of events

1. Endothelial injury or dysfunction
   • Caused by hyperlipidaemia, hypertension, smoking, diabetes, toxins, and disturbed blood flow at arterial branch points.
   • Endothelium becomes more permeable to lipids and leukocytes.
   • There is decreased nitric oxide, increased vasoconstriction, procoagulant activity, and leukocyte adhesion.
2. Lipoprotein accumulation in intima
   • LDL enters the intima and undergoes oxidation or other modification.
   • Modified LDL is cytotoxic, chemotactic for monocytes, and promotes inflammation.
3. Leukocyte adhesion and foam-cell formation
   • Monocytes adhere to endothelium, migrate into the intima, and become macrophages.
   • Macrophages ingest oxidized LDL through scavenger receptors and become foam cells.
   • T lymphocytes also enter and release cytokines.
4. Fatty streak formation
   • Aggregates of foam cells form the earliest visible lesion, the fatty streak.
5. Smooth-muscle migration and proliferation
   • Platelet-derived growth factor, fibroblast growth factor, and cytokines stimulate smooth-muscle cells to migrate from media to intima.
   • Smooth-muscle cells proliferate and may also accumulate lipid.
6. Extracellular matrix deposition
   • Smooth-muscle cells produce collagen, elastin, and proteoglycans.
   • This forms a fibrous cap over the lipid-rich necrotic core.
7. Complicated plaque formation
   • Plaques may undergo calcification, ulceration, rupture, thrombosis, intraplaque haemorrhage, or embolisation.

Morphology

Fatty streak

• Earliest lesion.
• Flat yellow streaks in the intima.
• Composed mainly of lipid-laden foam cells.
• Seen even in children and young adults.
• Does not significantly obstruct blood flow.

Atheromatous plaque

• Raised, white-to-yellow intimal lesion.
• Has:
  1. Fibrous cap: smooth-muscle cells, collagen, and inflammatory cells.
  2. Necrotic lipid core: cholesterol, cholesterol clefts, foam cells, cell debris, and fibrin.
• Common sites: abdominal aorta, coronary arteries, popliteal arteries, carotid bifurcation, and circle of Willis.

Complicated plaque

• Surface ulceration or erosion
• Superimposed thrombosis
• Intraplaque haemorrhage
• Calcification
• Atheroembolism
• Medial weakening with aneurysm formation

Complications

1. Stenosis of arteries causing chronic ischaemia:
   • Ischaemic heart disease
   • Cerebral infarction
   • Peripheral arterial disease
   • Renal ischaemia
2. Plaque rupture, erosion, or ulceration
   • Leads to acute thrombosis.
   • May cause myocardial infarction, stroke, or sudden cardiac death.
3. Atheroembolism
   • Cholesterol crystals or plaque fragments embolise to distal organs.
4. Aneurysm formation
   • Ischaemic atrophy of media weakens the vessel wall, especially in the abdominal aorta.
5. Haemorrhage into plaque
   • Enlarges plaque suddenly and may acutely obstruct the lumen.

2. Aneurysm: Definition, Types, and Abdominal Aortic Aneurysm

Definition

Types of aneurysm

According to wall involvement

1. True aneurysm
   • The dilated wall is formed by all layers of the vessel wall, although thinned.
   • Examples: atherosclerotic abdominal aortic aneurysm, syphilitic aneurysm, congenital aneurysm.
2. False aneurysm or pseudoaneurysm
   • A breach in the vascular wall leads to an extravascular haematoma communicating with the vascular lumen.
   • The wall of the sac is formed by surrounding tissue rather than all layers of the vessel wall.
   • Seen after trauma, surgery, or myocardial rupture.
3. Dissecting aneurysm or aortic dissection
   • Blood enters the media through an intimal tear and dissects between layers of the arterial wall.
   • Strictly, it is a dissection rather than a true aneurysm.

According to shape

1. Saccular aneurysm: localized spherical outpouching.
2. Fusiform aneurysm: circumferential dilatation involving a long segment.

According to etiology

• Atherosclerotic
• Congenital
• Syphilitic
• Mycotic or infective
• Traumatic
• Vasculitic
• Degenerative connective-tissue disorders, for example Marfan syndrome
• Hypertensive

Abdominal aortic aneurysm

Definition and site

Etiopathogenesis

1. Atherosclerosis
   • Produces chronic inflammation and destruction of elastic tissue and media.
   • Weakening of the aortic wall leads to progressive dilatation.
2. Smoking
   • Important risk factor.
3. Increasing age and male sex
4. Hypertension
5. Genetic predisposition and family history
6. Inflammation and proteolytic degradation
   • Macrophages release matrix metalloproteinases.
   • Elastin and collagen in the media are degraded.
7. Connective-tissue disorders
   • Marfan syndrome and Ehlers-Danlos syndrome can predispose, especially in younger patients.

Morphology

• Usually infrarenal.
• Usually fusiform, but may be saccular.
• Often large and associated with severe atherosclerosis.
• The lumen may contain a laminated mural thrombus.
• The wall shows:
  • Atherosclerotic plaques
  • Intimal calcification
  • Thinning and destruction of media
  • Chronic inflammation
  • Fibrosis

Clinical features

1. Pulsatile abdominal mass
2. Abdominal, back, or loin pain
3. Compression of adjacent structures, such as ureters or vertebrae
4. Distal ischaemia due to thromboembolism
5. Features of rupture: sudden severe abdominal or back pain, hypotension, shock, and collapse

Complications

1. Rupture
   • Most serious complication.
   • Causes massive retroperitoneal or intraperitoneal haemorrhage and death.
2. Mural thrombosis
   • Can cause acute arterial occlusion.
3. Atheroembolism or thromboembolism
   • May cause ischaemia of lower limbs, kidneys, bowel, or other organs.
4. Compression of nearby structures
   • Ureteric obstruction and hydronephrosis.
   • Vertebral erosion.
   • Venous compression.
5. Infection
   • Infected aneurysm may develop secondary to bacteraemia.

Aortic dissection: short note within classification

• Usually occurs in patients with hypertension, Marfan syndrome, or medial degeneration.
• An intimal tear allows blood to enter and split the media, creating a false lumen.
• It may rupture into the pericardial sac causing haemopericardium and cardiac tamponade, or into pleural/peritoneal cavity causing fatal haemorrhage.
• It can obstruct branches of the aorta, causing myocardial infarction, stroke, renal failure, or limb ischaemia.

3. Tetralogy of Fallot

Definition

Four components

1. Ventricular septal defect (VSD), usually large and membranous.
2. Right ventricular outflow tract obstruction, usually subpulmonary or infundibular stenosis, often with pulmonary valvular stenosis.
3. Overriding aorta, receiving blood from both ventricles.
4. Right ventricular hypertrophy, secondary to outflow obstruction.

• Pulmonary stenosis
• Right ventricular hypertrophy
• Overriding aorta
• Ventricular septal defect

Pathogenesis

• The fundamental developmental abnormality is anterior and cephalad displacement of the infundibular septum.
• This produces malalignment VSD and narrowing of the right ventricular outflow tract.
• Severity of cyanosis depends mainly on the degree of pulmonary stenosis.

Haemodynamic changes

• Obstruction to pulmonary outflow increases right ventricular pressure.
• Because the VSD is large, right ventricular pressure approaches left ventricular pressure.
• Blood shunts from right to left through VSD into the overriding aorta.
• Deoxygenated blood enters systemic circulation, resulting in cyanosis.

Morphology

Gross features

• Large VSD.
• Narrowed pulmonary outflow tract.
• Overriding aorta.
• Marked right ventricular hypertrophy.
• Heart may have a boot-shaped appearance on chest radiograph due to right ventricular hypertrophy and concavity of pulmonary artery segment.
• Pulmonary arteries are often hypoplastic.

Microscopy

• Right ventricular hypertrophy.
• Secondary changes related to chronic hypoxia may occur.

Clinical features

1. Cyanosis, usually appearing in infancy or early childhood
2. Dyspnoea on exertion
3. Squatting after exercise
   • Increases systemic vascular resistance.
   • Reduces right-to-left shunting.
   • Improves pulmonary blood flow.
4. Hypercyanotic spells or “tet spells”
   • Sudden worsening of cyanosis, dyspnoea, syncope, or seizures.
   • Often precipitated by crying, feeding, or exercise.
5. Clubbing of fingers and toes
6. Polycythaemia due to chronic hypoxia
7. Delayed growth and development
8. Systolic ejection murmur due to right ventricular outflow obstruction

Investigations

• Chest radiograph: boot-shaped heart with decreased pulmonary vascular markings.
• ECG: right axis deviation and right ventricular hypertrophy.
• Echocardiography: shows VSD, overriding aorta, and right ventricular outflow obstruction.
• Cardiac catheterisation: if necessary for anatomical and haemodynamic assessment.

Complications

1. Severe hypoxic spells and sudden death
2. Cerebral thrombosis due to polycythaemia
3. Brain abscess due to right-to-left shunt bypassing pulmonary filtration
4. Infective endocarditis
5. Heart failure
6. Arrhythmias after corrective surgery
7. Pulmonary regurgitation and right ventricular dilatation after repair

Treatment

• Definitive treatment is surgical correction:
  • Closure of VSD.
  • Relief of right ventricular outflow obstruction.
• Temporary palliative shunts may be used in selected infants.

4. Acute Myocardial Infarction

Case diagnosis

Acute ST-elevation myocardial infarction (STEMI)

Definition

Etiopathogenesis

Common mechanism

1. Atherosclerotic plaque in a coronary artery becomes unstable.
2. Plaque rupture, fissuring, erosion, or intraplaque haemorrhage occurs.
3. Platelets adhere, aggregate, and release mediators.
4. A thrombus forms and may completely occlude the coronary artery.
5. Prolonged ischaemia produces irreversible myocyte injury and coagulative necrosis.

Other causes

• Coronary artery spasm
• Coronary embolism
• Vasculitis
• Spontaneous coronary artery dissection
• Severe hypotension or hypoxaemia
• Severe anaemia or increased myocardial oxygen demand

Common sites

1. Left anterior descending artery: anterior wall of left ventricle, anterior two-thirds of interventricular septum, and apex.
2. Right coronary artery: posterior wall of left ventricle, posterior one-third of septum, and often right ventricle.
3. Left circumflex artery: lateral wall of left ventricle.

Laboratory investigations and diagnosis

ECG

• STEMI: ST-segment elevation in relevant leads.
• Later: T-wave inversion and pathological Q waves may develop.
• Serial ECGs are important.

Cardiac biomarkers

1. Cardiac troponin I and T
   • Most sensitive and specific biomarkers.
   • Rise: 3-4 hours.
   • Peak: about 24-48 hours.
   • Remain elevated: 7-10 days for troponin I and up to about 10-14 days for troponin T.
2. CK-MB
   • Rise: 3-6 hours.
   • Peak: about 18-24 hours.
   • Returns to normal: 48-72 hours.
   • Useful in detection of reinfarction because it normalizes relatively early.
3. Myoglobin
   • Rises early, within 1-2 hours.
   • Sensitive but not specific.
4. LDH
   • Rises later and is less useful now.

Other investigations

• Echocardiography: regional wall-motion abnormality, ejection fraction, mechanical complications.
• Coronary angiography: identifies culprit vessel.
• Complete blood count, glucose, renal function, lipid profile, and coagulation profile.

Sequential morphology in acute MI

Complications

Early complications

1. Arrhythmias
   • Most common early cause of death.
   • Ventricular fibrillation, ventricular tachycardia, heart block.
2. Left ventricular failure
   • Pulmonary oedema and cardiogenic shock.
3. Acute pericarditis
   • Fibrinous pericarditis, usually 1-3 days after transmural MI.
4. Extension or reinfarction

Mechanical complications

1. Papillary muscle rupture
   • Usually 2-7 days after infarction.
   • Causes acute severe mitral regurgitation and pulmonary oedema.
   • Posteromedial papillary muscle is vulnerable because of single blood supply.
2. Interventricular septal rupture
   • Causes acute VSD and left-to-right shunt.
3. Free-wall rupture
   • Causes haemopericardium and cardiac tamponade.
   • Often fatal.

Late complications

1. Ventricular aneurysm
2. Mural thrombus with systemic embolisation
3. Chronic heart failure
4. Dressler syndrome: autoimmune pericarditis occurring weeks after MI

5. Acute Rheumatic Fever and Rheumatic Heart Disease

Case diagnosis

Acute rheumatic fever with rheumatic carditis, producing mitral regurgitation

Definition

Etiology

• Occurs after pharyngitis caused by Streptococcus pyogenes, a group A beta-haemolytic streptococcus.
• It typically follows throat infection after a latent period of approximately 2-3 weeks.
• It does not usually follow streptococcal skin infection.

Pathogenesis

1. Group A streptococci possess M proteins and other antigens.
2. Antibodies and T cells directed against streptococcal antigens cross-react with host tissues.
3. Cross-reactivity occurs with cardiac myosin, valvular endothelium, and other connective tissues.
4. This produces inflammatory lesions in heart, joints, skin, subcutaneous tissue, and central nervous system.
5. Recurrent attacks cause progressive fibrosis and chronic valvular deformity.

Clinical features and Jones criteria

Major criteria

1. Migratory polyarthritis
2. Carditis or valvulitis
3. Sydenham chorea
4. Erythema marginatum
5. Subcutaneous nodules

Minor criteria

• Fever
• Arthralgia
• Raised ESR or CRP
• Prolonged PR interval on ECG

Requirement for diagnosis

• Two major criteria, or
• One major and two minor criteria.

Evidence of preceding streptococcal infection

1. Positive throat culture or rapid antigen test
2. Raised antistreptolysin-O titre
3. Raised anti-DNase B titre
4. Recent scarlet fever

Cardiac pathology

Acute rheumatic pancarditis

1. Pericarditis

• Serofibrinous or fibrinous pericarditis.
• Produces a “bread-and-butter” appearance due to fibrin deposition.

2. Myocarditis

• Characterized by Aschoff bodies, the pathognomonic lesion.
• Myocarditis may cause arrhythmias and cardiac failure.

3. Endocarditis and valvulitis

• Small sterile vegetations called verrucae occur along lines of valve closure.
• Mitral valve is most commonly affected, followed by aortic valve.
• Acute valvulitis causes mitral regurgitation.

Aschoff body

• Central fibrinoid necrosis of collagen.
• Surrounding lymphocytes and plasma cells.
• Activated macrophages called Anitschkow cells.
• Multinucleated giant cells may be present.

Chronic rheumatic heart disease

Valvular changes

• Leaflet thickening
• Commissural fusion
• Chordae tendineae thickening, shortening, and fusion
• Calcification in late disease

Common lesion

MacCallum plaques

• Irregular subendocardial thickenings in the left atrium.
• Usually located in the posterior wall.
• Caused by regurgitant jets striking the endocardium.
• Show oedema, fibrinoid change, and fibrosis.

Investigations

1. Throat swab culture or rapid antigen detection test
2. ASO titre and anti-DNase B titre
3. ESR and CRP: elevated
4. ECG: prolonged PR interval may occur
5. Echocardiography with Doppler: valvulitis, mitral/aortic regurgitation, chamber dilatation
6. Chest radiograph: cardiomegaly or pulmonary congestion in severe carditis
7. Complete blood count: may show leukocytosis

Complications

• Chronic mitral stenosis or mitral regurgitation
• Atrial fibrillation
• Left atrial thrombus and systemic embolism
• Pulmonary hypertension
• Right-sided heart failure
• Infective endocarditis on damaged valves

6. Infective Endocarditis

Case diagnosis

Subacute infective endocarditis, probably involving a previously abnormal mitral or aortic valve and commonly caused by viridans streptococci.

Definition

Predisposing factors

1. Pre-existing valvular heart disease:
   • Rheumatic valvular disease
   • Mitral valve prolapse
   • Calcific aortic stenosis
   • Congenital heart disease
2. Prosthetic heart valves
3. Previous infective endocarditis
4. Intravenous drug abuse
5. Indwelling intravascular catheters
6. Haemodialysis
7. Immunosuppression
8. Dental procedures causing transient bacteraemia

Classification and etiological agents

Pathogenesis

1. Endothelial injury occurs on a valve or endocardial surface because of turbulent blood flow, congenital defect, or degenerative valvular disease.
2. Platelets and fibrin deposit at the damaged site, producing sterile nonbacterial thrombotic endocarditis-like deposits.
3. Transient or persistent bacteraemia occurs, for example after dental extraction.
4. Organisms adhere to the damaged endocardium.
5. Organisms proliferate within platelet-fibrin thrombi, forming infected vegetations.
6. The vegetations are poorly penetrated by host immune cells and antibiotics because they are avascular.
7. Local destruction and embolisation may follow.

Morphology

Vegetations

• Large, irregular, friable, bulky masses on valve cusps.
• Often along the line of closure.
• Composed of fibrin, inflammatory cells, necrotic debris, and colonies of microorganisms.
• May destroy valve leaflets, chordae tendineae, or extend into adjacent myocardium.

Valve involvement

• Mitral and aortic valves are commonly affected in left-sided disease.
• Tricuspid valve is common in intravenous drug users.
• Prosthetic valves may develop infection at the valve ring, leading to dehiscence.

Histology

• Fibrin and platelets.
• Acute inflammatory infiltrate in acute IE.
• Organisms demonstrable by Gram stain, special stains, culture, or molecular tests.
• Underlying valve destruction and possible abscess formation.

Clinical features

1. Fever with chills and malaise
2. New or changing heart murmur
3. Tachycardia and signs of valvular regurgitation
4. Splenomegaly, especially in subacute disease
5. Petechiae and splinter haemorrhages
6. Osler nodes: painful nodules on finger or toe pads
7. Janeway lesions: painless erythematous lesions on palms and soles
8. Roth spots: retinal haemorrhages with pale centres
9. Anaemia of chronic disease
10. Embolic manifestations, such as stroke, renal infarct, splenic infarct, or pulmonary emboli in right-sided IE

Diagnosis

Blood cultures

• Obtain at least three sets of blood cultures from separate venepuncture sites before antibiotics, if the patient is stable.
• Persistent bacteraemia with a typical organism strongly supports diagnosis.

Echocardiography

• Transthoracic echocardiography may show vegetations.
• Transoesophageal echocardiography is more sensitive for small vegetations, prosthetic valves, abscesses, and valve dehiscence.

Duke criteria: simplified

Major criteria

1. Typical positive blood cultures.
2. Evidence of endocardial involvement:
   • Vegetation on echocardiography
   • Abscess
   • New partial dehiscence of prosthetic valve
   • New valvular regurgitation

Minor criteria

• Predisposition
• Fever
• Vascular phenomena
• Immunological phenomena
• Microbiological evidence not fulfilling a major criterion

Complications

Cardiac

1. Valvular destruction causing acute regurgitation and heart failure
2. Perivalvular abscess
3. Myocardial abscess
4. Conduction disturbances due to septal abscess
5. Prosthetic-valve dehiscence
6. Heart failure and death

Embolic and systemic

1. Septic emboli causing infarcts or abscesses in brain, kidney, spleen, and lungs
2. Mycotic aneurysm
3. Meningitis or brain abscess
4. Immune-complex glomerulonephritis
5. Splenomegaly
6. Disseminated infection and sepsis

Types of non-infective vegetations: differential point