Systemic Pathology - Heart Diseases

Definition

Ischemic Heart Disease (IHD), also called Coronary Artery Disease (CAD), is a group of clinical syndromes resulting from inadequate blood supply (ischemia) to the myocardium due to imbalance between coronary blood supply and myocardial demand, most commonly caused by atherosclerotic narrowing of the coronary arteries.

Classification of IHD

Risk factors of IHD are the same as atherosclerosis (atherosclerosis underlies >90% of IHD).

Non-Modifiable Risk Factors

Modifiable Risk Factors

Other Factors

• Metabolic Syndrome — insulin resistance + obesity + dyslipidemia + HTN
• Hyperhomocysteinemia — endothelial toxicity
• Chronic Inflammation — elevated CRP, IL-6
• Type A Personality / Stress — sympathetic overactivity
• OCP use — especially with smoking; Cocaine — coronary vasospasm

Pathogenesis Overview

IHD results from reduced myocardial O₂ supply relative to myocardial O₂ demand. Most common cause: atherosclerosis of coronary arteries (90-95%).

Step 1: Endothelial Dysfunction

• Caused by: HTN, smoking, hyperlipidemia, DM
• Endothelium becomes permeable to lipoproteins
• ↓Nitric Oxide (NO) → loss of vasodilation
• ↑Adhesion molecules (VCAM-1, ICAM-1, E-selectin)

Step 2: Lipid Accumulation

• LDL cholesterol enters intima → gets oxidized (ox-LDL)
• Ox-LDL is chemotactic for monocytes
• Monocytes → macrophages → engulf ox-LDL → Foam Cells

Step 3: Plaque Formation (Atheroma)

• SMCs migrate from media to intima, produce collagen
• Fibrous cap (collagen + SMCs) over lipid-rich necrotic core
• → Fibrofatty plaque / Atheroma

Step 4: Plaque Complications

Step 5: Myocardial Ischemia

• Subendocardium affected first (watershed zone, highest pressure)
• Ischemia → ↑ADP production failure → anaerobic glycolysis → lactic acid → cell death
• Prolonged ischemia → coagulative necrosis → MI

Causes of Precordial Chest Pain

Clinical Features of MI

A. Chest Pain (Hallmark)

B. Associated Symptoms

• Diaphoresis (profuse sweating) — most common associated symptom
• Nausea/vomiting — especially inferior MI
• Dyspnea — LV failure
• Palpitations — arrhythmias
• Sense of impending doom

C. Physical Signs

Definition

Angina Pectoris = clinical syndrome of transient myocardial ischemia causing episodic chest pain without irreversible necrosis.

Classification

CCS Grading of Stable Angina

Angina vs. MI — Key Differences

Definition

Myocardial Infarction (MI) = irreversible injury (necrosis) of myocardial cells due to prolonged severe ischemia, most commonly from acute coronary artery occlusion (plaque rupture + thrombosis).

Classification

Clinical Features

Symptoms

• Severe crushing retrosternal chest pain (>20-30 min, not relieved by NTG)
• Radiation: left arm, jaw, neck, epigastrium, back
• Diaphoresis, nausea/vomiting, dyspnea, palpitations, impending doom

Physical Signs

Atypical Presentations (15-30%)

Pathogenesis of MI

Step 1: Vulnerable Plaque

• Thin fibrous cap + large lipid-rich necrotic core
• Macrophage-secreted MMPs degrade collagen

Step 2: Plaque Rupture or Erosion

• Plaque rupture (~60-70%): Cap disruption → exposes lipid core to blood
• Plaque erosion (~30-40%): Endothelial denudation
• Calcified nodule (~2-5%): Rare

Step 3: Thrombosis

• Exposed collagen + tissue factor → platelet adhesion (GP Ib, GP IIb/IIIa)
• Platelet activation → TXA2, ADP release → more recruitment
• Coagulation cascade → fibrin mesh → occlusive thrombus

Step 4: Myocardial Necrosis

• Occlusion >20-30 min → irreversible injury begins
• Necrosis starts subendocardium → spreads outward transmurally by 6 hours

Morphologic Changes (Timeline)

MI produces coagulative necrosis — the most common pattern of tissue necrosis.

Fates / Outcomes of MI

Definition

Chronic IHD (Ischemic Cardiomyopathy) = dilated cardiomyopathy from progressive, chronic myocardial ischemia and repeated ischemic injury, leading to diffuse myocardial fibrosis, ventricular dilation, and progressive heart failure.

How It Develops

1. Chronic progressive atherosclerosis → multi-vessel disease
2. Repeated subclinical ischemic episodes → cumulative myocyte death
3. Hibernating myocardium → viable but downregulated contractile function
4. Replacement fibrosis → dead myocytes → collagen scar
5. Interstitial fibrosis → chronic ischemia → diffuse collagen
6. LV remodeling → dilation, spherical shape, wall thinning
7. Neurohormonal activation (RAAS, sympathetic) → further remodeling
8. Progressive heart failure

Clinical Features

• Progressive exertional dyspnea and fatigue
• Orthopnea and PND
• Peripheral edema
• Cardiomegaly
• Biventricular failure in advanced cases

Lab Diagnosis of MI

1. Cardiac Biomarkers (Most Important)

2. ECG Findings

ECG Localization

3. Other Tests

• CBC: Leukocytosis (12-15K) with neutrophilia
• ESR/CRP: Elevated (inflammatory response)
• Glucose: Often elevated (stress)
• BNP/NT-proBNP: Elevated if HF develops

4. Imaging

• Echocardiography: Regional wall motion abnormalities, EF
• Coronary angiography: Definitive — shows occlusion site
• CXR: Cardiomegaly, pulmonary congestion
• Cardiac MRI: Late gadolinium enhancement

Cardiac Biomarkers — Detailed Interpretation

Visual Timeline

Complications of MI

1. Arrhythmias (Most Common — ~90%)

2. Acute Heart Failure / Cardiogenic Shock

• >40% LV muscle loss → cardiogenic shock
• Pulmonary edema, hypotension, oliguria

3. Cardiac Rupture (Day 3-7)

4. Mural Thrombus

• Endocardial damage + stasis → thrombus
• Systemic embolization → stroke, renal infarction

5. Ventricular Aneurysm

• Thinned fibrotic scar bulges during systole
• Persistent ST elevation; HF; mural thrombus
• Does NOT rupture (fibrous = strong)

6. Pericarditis

7. Other

• LV remodeling, chronic ischemic cardiomyopathy
• RV infarction (proximal RCA) → hypotension + JVD + clear lungs

Definition

Hypertension = persistently elevated systemic arterial BP (ACC/AHA 2017):

Classification

By Severity

Causes of Secondary Hypertension

End-Organ Damage

• Heart: LV hypertrophy → HF; IHD; aortic dissection
• Kidneys: Nephrosclerosis → CKD
• Brain: Stroke, vascular dementia, encephalopathy
• Eyes: Hypertensive retinopathy
• Vessels: Atherosclerosis, aortic aneurysm

Classification of CHD

By Hemodynamic Status:

By Frequency:

• VSD — most common CHD overall (~30%)
• ASD — most common in adults
• PDA — most common in premature infants
• TOF — most common cyanotic CHD in children

Tetralogy of Fallot (TOF)

Pathophysiology

• RVOTO → ↑RV pressure → R→L shunt through VSD
• Deoxygenated blood enters aorta → systemic cyanosis
• Severity depends on degree of RVOTO

Clinical Features

• Cyanosis (central) — at birth or within months
• Tet spells — episodic hypercyanotic episodes (squatting relieves)
• Clubbing, growth retardation, exercise intolerance
• Polycythemia (compensatory ↑RBC)
• Boot-shaped heart (coeur en sabot) on CXR
• Pulmonary murmur (from stenosis)

Definition

Rheumatic Fever (RF) = acute, systemic, inflammatory, non-suppurative (immune-mediated) disease occurring 2-4 weeks after Group A Streptococcal pharyngitis. Primarily affects heart, joints, skin, brain, subcutaneous tissue.

Pathogenesis

Step 1: GAS Pharyngitis

• Group A Streptococcus with virulent M protein (antiphagocytic)

Step 2: Immune Response

• Anti-M protein antibodies produced
• Cross-react with human tissue proteins due to structural similarity = molecular mimicry

Step 3: Cross-Reactive Targets

Step 4: Tissue Damage

• Cell-mediated: CD4+ T-cells infiltrate → cytokines → inflammation
• Humoral: Cross-reactive antibodies → complement → tissue damage
• Aschoff bodies form in heart (pathognomonic)

Step 5: Cardiac Damage

• Valves most affected (especially mitral, then aortic)
• Acute: Verrucous endocarditis (warty vegetations along lines of closure)
• Chronic: Valvular scarring → stenosis/regurgitation → chronic RHD

Jones Criteria

Major Criteria (“JONES”)

Mnemonic: Joints • O (heart) • Nodules • Erythema • Sydenham

Minor Criteria

Evidence of Preceding GAS Infection

Etiopathogenesis of RHD

RHD is the chronic, irreversible valvular damage that results from repeated episodes of acute rheumatic fever. It is the long-term sequela of untreated/recurrent RF.

Etiology

• Group A Streptococcus (S. pyogenes) pharyngitis
• Untreated or recurrent infections increase risk of RHD
• Genetic susceptibility (HLA-DR7, HLA-DR4)
• Environmental factors (overcrowding, poverty, malnutrition)

Pathogenesis of Valvular Damage

Acute Phase (Rheumatic Valvulitis)

• Verrucous (fibrin) vegetations on valve leaflets
• Small (1-3mm), warty, along lines of closure (not surfaces)
• Aschoff bodies in myocardium
• Aschoff cells + Anitschkow cells

Chronic Phase (Rheumatic Heart Disease)

• Repeated episodes → progressive fibrosis
• Valve leaflets become thickened, calcified, fused
• Chordae tendineae shortened and thickened
• Result: Mitral stenosis (most common), mitral regurgitation, aortic regurgitation

Most Common Valvular Lesions in RHD

Complications of Rheumatic Fever

1. Cardiac Complications (Most Important)

2. Other Complications

Inflammatory Diseases of the Heart

Causes of Pericarditis

Aschoff Body

Structure

Aschoff body undergoes three stages:

Aschoff Cells

• Large cells with abundant cytoplasm
• May be multinucleated
• Found within the Aschoff body
• Modified macrophages / histiocytes

Location

• Myocardium (especially around blood vessels)
• Pericardium
• Atrial appendage (most common site for biopsy)

Significance

• Confirmatory of active rheumatic carditis
• Found in >90% of fatal RF cases
• May persist for months to years

Anitschkow Cell

Features

• Modified macrophage with abundant cytoplasm
• Nucleus has a central, wavy, ribbon-like bar of chromatin that resembles a caterpillar in longitudinal section
• In cross-section, the chromatin appears as an owl-eye pattern
• Pathognomonic cell of rheumatic fever

Infective Endocarditis (IE)

Infective Endocarditis = infection of the endocardial surface of the heart, primarily involving the heart valves. Characterized by formation of vegetations (masses of fibrin, platelets, bacteria, and inflammatory cells) on the valves.

Classification

Etiopathogenesis of Infective Endocarditis

Etiology

Pathogenesis — Step by Step

Step 1: Endocardial Injury

• Pre-existing valve damage (RHD, degenerative, prosthetic)
• Causes turbulent blood flow → platelet-fibrin thrombus (non-bacterial thrombotic endocarditis - NBTE)
• Provides a “bed” for bacterial adhesion

Step 2: Bacteremia

• Transient bacteremia from: dental procedures, GI/GU procedures, IV drug use, skin infections, surgical wounds
• Most people have transient bacteremia without consequences

Step 3: Bacterial Adhesion and Colonization

• Bacteria adhere to platelet-fibrin surface
• Streptococci: bind via fibronectin-binding proteins
• S. aureus: can bind directly to intact endothelium (more aggressive)

Step 4: Vegetation Growth

• Bacteria multiply within the platelet-fibrin mesh
• Protected from phagocytes and antibiotics
• Vegetations grow → can be large (>1cm) and friable
• Bacteria continuously shed → persistent bacteremia

Step 5: Complications

• Local: Valve destruction, abscess, perforation
• Embolization: Septic emboli → kidneys, spleen, brain, extremities
• Immunological: Glomerulonephritis, Osler nodes, Roth spots

Complications of Infective Endocarditis

1. Cardiac Complications

2. Embolic Complications (Septic Emboli)

3. Immunological Complications

• Glomerulonephritis (immune complex deposition)
• Osler nodes (painful nodules on fingers/toes — immune)
• Roth spots (retinal hemorrhages — immune)
• Clubbing (chronic cases)

4. Other Complications

• Septicemia / Sepsis → organ failure
• Heart failure ← valve destruction
• Persistent fever
• Anemia of chronic disease

Vegetation

Vegetation = a mass composed of fibrin, platelets, microorganisms (in infective endocarditis), and inflammatory cells that forms on the endocardial surface (usually on heart valves).

Composition

• Fibrin meshwork (major structural component)
• Platelets
• Bacteria / microorganisms (in infective endocarditis)
• Inflammatory cells (neutrophils, macrophages)
• Dead/necrotic tissue

Characteristics

Vegetative Heart Diseases — Causes

Pericarditis — Short Note

Pericarditis = inflammation of the pericardium (double-layered serous membrane surrounding the heart).

Etiology

• Idiopathic/Viral (most common in developed countries) — Coxsackievirus B
• Tuberculosis (most common in developing countries)
• Post-MI (acute or Dressler syndrome)
• Bacterial (Staph, Strep)
• Autoimmune (SLE, RA)
• Neoplastic (metastatic cancer)
• Uremia (renal failure)

Types

Morphology

• Acute fibrinous: “Bread and butter” pericardium; shaggy, yellow fibrin on surfaces
• Pericardial effusion: Fluid accumulation (>50ml abnormal)
• Constrictive: Thickened, fibrotic pericardium; may calcify

Clinical Features

• Pericarditic chest pain: Sharp, pleuritic, worse on inspiration, relieved by sitting forward
• Pericardial friction rub: Scratchy sound on auscultation (pathognomonic)
• Fever, malaise
• ECG: Diffuse ST elevation (concave up) + PR depression

Complications

• Cardiac tamponade (rapid fluid accumulation → compresses heart)
• Constrictive pericarditis (chronic fibrosis)
• Recurrent pericarditis

Cardiomyopathy — Short Note

Cardiomyopathy = diseases of the myocardium associated with mechanical and/or electrical dysfunction, usually manifesting as inappropriate ventricular hypertrophy or dilation, in the absence of coronary artery disease, hypertension, or valvular disease.

Classification (WHO)

Dilated Cardiomyopathy (DCM)

Causes:

• Idiopathic (most common, ~50%)
• Alcoholic (most common acquired cause)
• Genetic (familial, ~30%) — titin, lamin, dystrophin mutations
• Myocarditis (viral, especially Coxsackievirus B)
• Peripartum cardiomyopathy
• Drug-induced (doxorubicin, cocaine)
• Nutritional (thiamine deficiency → wet beriberi, selenium)
• Ischemic (chronic IHD)

Morphology:

• All 4 chambers dilated; globular heart
• Hypertrophy then dilation
• Mural thrombus common
• Microscopic: myocyte hypertrophy, degeneration, fibrosis

Hypertrophic Cardiomyopathy (HCM)

Causes:

• Genetic (autosomal dominant) — mutations in sarcomeric proteins (β-myosin heavy chain, myosin-binding protein C, tropomyosin)
• Most common inherited cardiac disease

Morphology:

• Asymmetric septal hypertrophy (interventricular septum > LV free wall)
• ↑LV mass; small or normal cavity
• Myocyte disarray; interstitial fibrosis
• May cause LVOT obstruction

Restrictive Cardiomyopathy

Causes:

• Amyloidosis (most common in developed countries)
• Sarcoidosis
• Hemochromatosis (iron deposition)
• Endomyocardial fibrosis (most common worldwide)
• Lα storage diseases

Myocarditis — Short Note

Myocarditis = inflammation of the myocardium (heart muscle). Defined as an inflammatory infiltrate within the myocardium associated with myocyte necrosis not due to ischemia.

Etiology

Pathogenesis

Viral Myocarditis (Most Common)

• Phase 1: Viral infection → direct cytopathic effect on myocytes (viral binds receptors → cell lysis)
• Phase 2: Innate and adaptive immune response; NK cells, T-cells infiltrate; cytokine release; autoimmune damage via molecular mimicry
• Phase 3: Recovery or progression to dilated cardiomyopathy (chronic inflammation, fibrosis)

Morphology

• Gross: Enlarged, soft, flabby heart; pale areas; may have petechiae; mural thrombus
• Microscopic:
  • Lymphocytic infiltrate (viral) — most common pattern
  • Myocyte degeneration and necrosis
  • Interstitial edema
  • Eosinophilic infiltrate (drug hypersensitivity, Chagas, parasitic)
  • Granulomatous (sarcoid, giant cell)

Clinical Features

• Acute: Chest pain (pleuritic), dyspnea, palpitations, fatigue, fever, myalgia
• Can mimic MI (chest pain + elevated troponin + ECG changes)
• May present as: Heart failure, Arrhythmias, Sudden cardiac death, or Dilated cardiomyopathy
• Virchow’s triad-like: fulminant (days), acute (weeks), chronic (DCM)

Diagnosis

• Endomyocardial biopsy (gold standard) — Dallas criteria
• Cardiac MRI (non-invasive; edema + late gadolinium enhancement)
• Troponin elevated
• Echo: Dilated chambers, ↓EF
• Viral serology/PCR