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Ischemic Heart Disease (IHD) - 10 Mark Answer

Definition

IHD is synonymous with coronary artery disease (CAD) in over 90% of cases.

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Etiology / Risk Factors

• Hypertension
• Dyslipidemia (raised LDL, low HDL)
• Diabetes mellitus
• Cigarette smoking
• Obesity and sedentary lifestyle

• Age (males >45 yrs, females >55 yrs)
• Male sex
• Family history of premature CAD

• Increased demand: tachycardia, hypertension, hypertrophy
• Decreased supply: hypotension, anemia, carbon monoxide poisoning, coronary vasospasm (Prinzmetal angina), vasculitis, embolism

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Pathogenesis

1. Fixed (Chronic) Atherosclerotic Stenosis

• Stenosis of <70% lumen is typically asymptomatic
• >70% occlusion = "critical stenosis" - causes exertional angina (stable angina)
• >90% occlusion - may cause symptoms even at rest
• Clinically significant plaques occur in the first few cm of LAD, LCX, and along the RCA
• Slow progressive occlusion allows collateral circulation to develop, potentially preventing infarction

2. Acute Plaque Change (ACS trigger)

• Sudden plaque rupture, fissure, or erosion exposes thrombogenic subendothelial contents
• Triggers rapid platelet aggregation and thrombus formation
• Hemorrhage into plaque core can acutely expand the lesion
• Coronary vasospasm worsens luminal narrowing and can precipitate plaque disruption
• Vasospasm is triggered by: circulating adrenergic agonists, platelet products, imbalance of NO/endothelin, perivascular inflammatory mediators

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Clinical Syndromes of IHD

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Pathology of Myocardial Infarction

Cellular Sequence of Events:

• Seconds: Aerobic metabolism ceases; ATP falls; lactic acid accumulates
• Minutes: Loss of contractility (reversible)
• 20-40 minutes: Irreversible myocyte death (coagulative necrosis)
• Earliest sign: Disruption of sarcolemmal membrane - intracellular proteins (troponins, CK-MB) leak into bloodstream

Zone of Injury:

• Irreversible injury first appears in the subendocardial zone (most susceptible - last to receive blood, highest intramural pressure)
• With prolonged ischemia, necrosis advances as a "wavefront" toward epicardium (driven by edema, ROS, inflammatory mediators)

Histological Changes Over Time:

Reperfused Infarction:

• Hemorrhagic (due to vascular damage in reperfused zone)
• Shows contraction band necrosis microscopically - intense eosinophilic bands from calcium-induced hypercontracted sarcomeres fixed in tetanic state

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Clinical Features of Acute MI

• Chest pain: Severe, crushing, substernal; radiates to neck, jaw, epigastrium, or left arm; lasts minutes to hours; NOT relieved by nitrates or rest
• Silent MI (~25%): Common in diabetics (autonomic neuropathy) and the elderly
• Other features: Diaphoresis, nausea/vomiting (especially posterior wall MI), dyspnea, tachycardia, weak pulse
• Cardiogenic shock: Develops if >40% of LV is infarcted

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Investigations

ECG:

• STEMI: ST elevation in territory of affected artery; followed by Q wave development
• NSTEMI: ST depression or T wave inversion; no Q waves
• Unstable angina: May be normal or have transient changes; troponin negative

Cardiac Biomarkers (order of appearance):

Other Investigations:

• Echocardiography: wall motion abnormalities
• Coronary angiography: defines anatomy, guides PCI
• Chest X-ray: pulmonary edema, cardiac enlargement

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Complications of MI (Mnemonic: DREAD)

• Arrhythmias (most common cause of early death; VF is most lethal)
• Cardiogenic shock (>40% LV involvement)
• Acute mitral regurgitation (papillary muscle rupture, 3-5 days)
• Ventricular free wall rupture (3-7 days - cardiac tamponade)
• Ventricular septal defect (septal rupture)
• Mural thrombus (with risk of systemic embolism)

• Pericarditis (Dressler syndrome - weeks later, autoimmune)
• Ventricular aneurysm (thin scarred wall, persistent ST elevation)
• Chronic heart failure / ischemic cardiomyopathy

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Management

Immediate (within minutes of presentation):

• MONA: Morphine, Oxygen, Nitrates, Aspirin
• Antiplatelet: Aspirin 300 mg loading + P2Y12 inhibitor (clopidogrel/ticagrelor)
• Anticoagulation: Heparin or LMWH

Reperfusion (for STEMI - time is muscle):

• Primary PCI (percutaneous coronary intervention): Treatment of choice within 90 min of first medical contact; balloon angioplasty + stent
• Thrombolysis (fibrinolytics): If PCI not available within 120 min; use streptokinase or tPA (tissue plasminogen activator); contraindicated in recent surgery, bleeding risk, severe hypertension

Medical Therapy (ABCDE):

• A - Aspirin + ACE inhibitor (reduces remodeling, mortality)
• B - Beta-blockers (reduce heart rate, infarct size, arrhythmia risk)
• C - Cholesterol-lowering (high-intensity statins)
• D - Diabetes/Diet management
• E - Exercise (cardiac rehabilitation)

Surgical:

• CABG (coronary artery bypass graft surgery): For multivessel disease, left main stenosis, or failed PCI

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Prognosis

• ~800,000 Americans have MI annually; ~50% die
• Mortality has fallen 50% since 1963 due to risk factor control, aspirin, CCUs, PCI, thrombolysis
• Worse prognosis: large infarct, reduced EF, VT/VF, cardiogenic shock, diabetes, advanced age
• Early reperfusion is the single most important factor determining outcome

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Summary Table

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Ischemic Heart Disease (IHD) - Detailed MBBS Answer

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1. DEFINITION AND OVERVIEW

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2. ETIOLOGY AND RISK FACTORS

Primary Cause: Coronary Atherosclerosis

Risk Factors:

Note: The epidemic of obesity sweeping both high-income and low/middle-income countries is driving a resurgence of IHD globally.

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3. PATHOGENESIS

3a. Fixed (Chronic) Atherosclerotic Stenosis

• <70% stenosis: Typically asymptomatic at rest and with exertion
• >70% ("critical stenosis"): Reduces coronary flow reserve; causes predictable stable angina on exertion
• >90% stenosis: Can cause ischemia at rest - a form of unstable angina
• Plaques typically affect the first few cm of the LAD and LCX from their takeoff, and along the entire RCA
• Secondary branches (diagonal branches of LAD, obtuse marginals of LCX, posterior descending of RCA) may also be involved
• Gradual occlusion over years allows collateral circulation to develop, potentially protecting from infarction even with complete vessel closure
• Rapid acute occlusion gives no time for collaterals - infarction results

3b. Acute Plaque Change - Trigger of ACS

1. Plaque rupture, fissure, erosion, or ulceration exposing thrombogenic plaque core or subendothelial basement membrane
2. Rapid platelet aggregation and thrombus formation at the site of disruption
3. Hemorrhage into the plaque core acutely expands its volume, worsening stenosis
4. Vasospasm further reduces luminal caliber; also mechanically promotes plaque disruption

• Circulating adrenergic agonists (stress, cocaine use)
• Platelet-derived mediators (thromboxane A2, serotonin)
• Imbalance between NO (vasodilator) and endothelin (vasoconstrictor) due to endothelial dysfunction
• Perivascular inflammatory cell mediators

Most critically, a completely obstructive thrombus over a disrupted plaque causes transmural infarction (STEMI), while partial obstruction typically causes subendocardial infarction (NSTEMI).

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4. CLINICAL SYNDROMES OF IHD

4a. Stable (Chronic) Angina

• Due to fixed >70% stenosis; consistently triggered by exertion, cold, or emotion
• Pain: substernal tightness/pressure, radiates to left arm/jaw; relieved by rest or nitroglycerin within 5 min
• ECG during attack: transient ST depression; returns to normal between attacks
• Troponin: normal (no myocyte death)

4b. Unstable Angina (UA)

• Defined by any of: (1) chest pain at rest lasting >10 min, (2) new-onset severe angina, or (3) crescendo pattern - increasing frequency, severity, or duration
• Caused by plaque rupture/erosion + non-occlusive thrombus + vasospasm
• Troponin: normal (distinguishes UA from NSTEMI)
• ECG: transient ST depression or T-wave changes; or normal

4c. NSTEMI (Non-ST Elevation MI)

• Same mechanism as UA but thrombus is sufficiently obstructive to cause subendocardial infarction
• Troponin: elevated (dynamic rise and fall characteristic)
• ECG: ST depression, deep T-wave inversion (≥0.3 mV); no ST elevation; no Q waves
• hsTroponin elevation >99th percentile + clinical history = NSTEMI diagnosis

4d. STEMI (ST Elevation MI)

• Complete, persistent occlusion of a coronary artery
• Causes transmural (full-thickness) infarction
• ECG: ST elevation in affected territory → Q waves develop over 12-24 hours
• Troponin: markedly elevated
• Medical emergency - time from symptom onset to reperfusion is the key determinant of outcome

4e. Vasospastic (Prinzmetal) Angina

• Caused by focal spasm of an epicardial coronary artery - may occur on a background of mild atherosclerosis or in a normal artery
• Pain occurs at rest, typically early morning; not exertional
• ECG during attack: ST elevation (distinguishes from stable angina); resolves with nitroglycerin
• Diagnosis confirmed by: coronary angiography showing transient spasm; provoked by intracoronary acetylcholine or hyperventilation
• Associated with: migraine, Raynaud's phenomenon, cigarette smoking
• Treatment: Calcium channel blockers (first-line); long-acting nitrates; aspirin may worsen spasm (prostacyclin-related mechanism)
• Prognosis: 5-year survival ~90-95%, but ~20% develop MI

4f. Sudden Cardiac Death (SCD)

• Most commonly occurs due to ventricular fibrillation from ischemia-induced myocardial electrical irritability
• Accounts for 80-90% of pre-hospital MI-related deaths (within 1 hour of onset)
• Underlying substrate: usually severe coronary artery disease; may occur without preceding infarction
• In younger patients: inherited channelopathies (long QT, Brugada) or structural anomalies

4g. Chronic IHD / Ischemic Cardiomyopathy

• Progressive cardiac decompensation from accumulated ischemic injury
• From previous infarction(s) or chronic "stunned/hibernating" myocardium
• Manifests as progressive CHF with reduced ejection fraction

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5. TOPOGRAPHIC DISTRIBUTION OF MI BY VESSEL INVOLVED

Right dominance (90% of individuals): PDA arises from RCA. So RCA occlusion = posterior LV + posterior septum involvement.

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6. PATHOLOGY OF MYOCARDIAL INFARCTION

6a. Zones of Necrosis

• Transmural infarct: Full-thickness necrosis; caused by complete epicardial artery occlusion; associated with STEMI
• Subendocardial infarct: Limited to inner 1/3 of myocardium; from partial/transient obstruction or global hypotension superimposed on multivessel disease; NSTEMI
• Microinfarcts: From small intramyocardial vessel disease or emboli

1. Is the last zone to receive blood delivered via epicardial vessels
2. Is subjected to high intramural pressures that impede inflow

6b. Sequential Histological Changes - (HIGH-YIELD)

Coagulative necrosis is the type of necrosis seen in MI - cell outlines preserved but nuclei disappear.

6c. Reperfused Infarction

• Gross: Hemorrhagic (blood leaks into tissue from vascular damage)
• Microscopy: Contraction band necrosis - intense eosinophilic cross-striations of hypercontracted sarcomeres; caused by calcium influx into irreversibly injured cells at the moment of reperfusion; sarcomeres fixed in tetanic state

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7. INVESTIGATIONS

7a. Electrocardiography

• V1-V4: Anterior (LAD)
• I, aVL, V5-V6: Lateral (LCX)
• II, III, aVF: Inferior (RCA)
• V7-V9 (posterior leads): Posterior (RCA/LCX)
• V1, V4R: Right ventricular (RCA)

7b. Cardiac Biomarkers - Detailed

"Troponin" on ECG strips: With reperfusion, both troponin and CK-MB peak earlier due to rapid washout from necrotic tissue - this is a hallmark of successful reperfusion.

Causes of elevated troponin OTHER than MI (important for differential): pulmonary embolism, myocarditis, sepsis, renal failure, stroke, cardiac contusion, Takotsubo cardiomyopathy

7c. Other Investigations

• Echocardiography: Regional wall motion abnormalities (hypokinesia, akinesia, dyskinesia); assess LV function (EF); detect pericardial effusion, VSD, MR
• Coronary angiography: Gold standard to define anatomy; guides PCI or CABG decision
• Stress testing (for stable angina): TMT (treadmill test) - ST depression ≥1mm at submaximal HR indicates significant ischemia; pharmacological stress echo for those who cannot exercise
• Cardiac CT Angiography: Non-invasive; high negative predictive value for ruling out CAD
• Chest X-ray: Pulmonary edema (perihilar haziness, Kerley B lines), cardiomegaly
• CBC, RFT, LFT, lipid profile, blood glucose, HbA1c: Baseline and risk factor assessment

7d. Risk Stratification (for NSTE-ACS)

• Age ≥65
• ≥3 CAD risk factors
• Known CAD (stenosis ≥50%)
• Aspirin use in past 7 days (indicates aspirin-resistant platelet activation)
• ≥2 anginal events in 24 h
• Elevated serum cardiac markers
• ST changes ≥0.5 mm

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8. COMPLICATIONS OF MYOCARDIAL INFARCTION

Early Complications (hours to days):

• VF - most common cause of early death; occurs within first hour
• VT - often pre-VF
• AF/Atrial flutter - from atrial distension/ischemia
• Heart block/Brady - especially with inferior MI (RCA supplies SA and AV nodes)
• Accelerated idioventricular rhythm (AIVR) - benign reperfusion arrhythmia

• Occurs when >40% of LV myocardium infarcted
• Features: hypotension, oliguria, pulmonary edema, cold clammy extremities
• Mortality: 50-70% despite treatment
• Management: intra-aortic balloon pump, emergent PCI, vasopressors (dopamine/noradrenaline)

• Day 3-7 post-MI; posteromedial papillary muscle more commonly involved (single RCA supply vs anterolateral which has dual supply)
• Sudden onset of flash pulmonary edema + new loud pansystolic murmur
• Emergent surgical repair required

• Day 3-7 post-MI; most common rupture site
• New loud pansystolic murmur + step-up in O2 saturation from RA to RV on catheterization
• Surgical repair + IABP

• Day 3-7; least common but most lethal rupture
• Causes hemopericardium and acute cardiac tamponade
• Presents with sudden cardiovascular collapse (electromechanical dissociation/PEA)
• Urgent pericardiocentesis + surgery

These three rupture complications are most likely 3-7 days after MI when enzymatic lysis of necrotic myocardium is maximal and the infarct zone has converted to soft friable granulation tissue.

• Forms over akinetic endocardium (especially anterior MI with apical involvement)
• Risk of systemic embolization (stroke, renal/mesenteric infarction)
• Anticoagulate with LMWH/warfarin for 3-6 months

• Associated with inferior STEMI (RCA occlusion)
• Triad: hypotension + raised JVP + clear lungs (without pulmonary edema)
• ECG: ST elevation in V4R (right-sided lead)
• Management: IV fluids (preload-dependent); avoid nitrates and diuretics

Late Complications (weeks to months):

• Occurs 2-10 weeks after MI
• Autoimmune pericarditis (antibodies against damaged myocardial antigens)
• Features: pleuritic chest pain, fever, pericardial friction rub, pericardial/pleural effusion
• Treatment: NSAIDs, colchicine; steroids for refractory cases

• Thinned, scarred, non-contractile LV wall that bulges paradoxically
• ECG: Persistent ST elevation (>2 weeks after MI without evolution)
• Echo: dyskinetic wall segment
• Complications: mural thrombus, arrhythmias, CHF
• Large symptomatic aneurysms: surgical aneurysmectomy

• Progressive ventricular dilation and remodeling
• Reduced EF, dyspnea, exercise intolerance, recurrent hospitalizations

• Day 1-3 after transmural MI (fibrinous pericarditis over necrotic epicardium)
• Pleuritic chest pain, friction rub, diffuse ST elevation
• Treatment: aspirin (NSAIDs cautious due to impaired healing)

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9. MANAGEMENT

9a. Initial Management of ACS (Universal)

• Morphine: 2-4 mg IV for pain, anxiety, preload reduction (caution - may mask symptoms)
• Oxygen: Only if SpO2 <90% or in respiratory distress; not routine
• Nitrates: Sublingual GTN 0.3-0.6 mg; if not relieved x3 doses → IV nitroglycerin at 5-10 µg/min, titrating up
  • Contraindications: Hypotension, RV infarction, recent PDE-5 inhibitor use (sildenafil/vardenafil within 24 h; tadalafil within 48 h), severe aortic stenosis
• Aspirin: 300 mg loading dose (chew); then 75-100 mg daily indefinitely

9b. Antiplatelet Therapy

• Dual Antiplatelet Therapy (DAPT): Aspirin + P2Y12 inhibitor
• P2Y12 options:
  • Ticagrelor 180 mg loading, 90 mg BD (preferred - faster onset, not a prodrug)
  • Clopidogrel 300-600 mg loading, 75 mg daily (consider if ticagrelor not available; ~30% are poor metabolizers due to CYP2C19 polymorphism)
  • Prasugrel 60 mg loading, 10 mg daily (avoid in prior stroke/TIA, age >75, weight <60 kg)
• Duration of DAPT: 12 months for ACS; may extend to >12 months in high thrombotic risk; shorten to 3-6 months if high bleeding risk

9c. Anticoagulation

1. UFH (Unfractionated heparin): Bolus + infusion; easily reversible with protamine
2. LMWH (Enoxaparin): SC once/twice daily; preferred for NSTE-ACS; no reversal agent until fondaparinux
3. Fondaparinux (factor Xa inhibitor): Once daily SC; less bleeding than enoxaparin; avoid in severe renal failure
4. Bivalirudin (direct thrombin inhibitor): IV; used during PCI; less major bleeding

9d. Reperfusion Strategy

• Alteplase (tPA): Fibrin-specific; accelerated regimen: 15 mg IV bolus then 0.75 mg/kg over 30 min then 0.5 mg/kg over 60 min
• Streptokinase: Non-fibrin-specific; 1.5 million units IV over 60 min; cheaper; cannot be given twice (antibodies formed)
• Tenecteplase (TNK-tPA): Single weight-based IV bolus; most convenient

• Prior intracranial hemorrhage or hemorrhagic stroke at any time
• Ischemic stroke within 3 months
• Active bleeding (excluding menses)
• Suspected aortic dissection
• Significant head trauma or intracranial neoplasm within 3 months
• Severe uncontrolled hypertension (>180/110 despite treatment)

• Invasive strategy (angiography within 24-72 h) for high-risk patients
• Conservative strategy for low-risk patients initially managed medically

9e. Anti-Ischemic Medical Therapy

• Reduce heart rate and contractility → decreased myocardial O2 demand
• Reduce infarct size, arrhythmias, risk of reinfarction
• Start early (within 24 h) in absence of contraindications
• Contraindications: PR >0.24 s, 2nd/3rd degree AV block, HR <50/min, SBP <90 mmHg, Killip class III/IV heart failure, severe reactive airways disease

• Venodilation → reduce preload → reduce O2 demand
• Coronary vasodilation
• Sublingual for acute attacks; IV for ongoing ischemia

• Used when beta-blockers contraindicated
• Non-dihydropyridine (diltiazem, verapamil): slow HR, used for angina; avoid in LV dysfunction or HF
• Dihydropyridine (amlodipine): vasodilation; use with beta-blocker for stable angina; avoid short-acting nifedipine alone

9f. Secondary Prevention (Long-term)

9g. Surgical - CABG (Coronary Artery Bypass Grafting)

• Left main coronary artery disease (≥50% stenosis)
• Three-vessel disease with impaired LV function (EF <35-50%)
• Two-vessel disease involving proximal LAD with impaired EF
• Failed PCI
• Anatomy unsuitable for PCI

• Left internal mammary artery (LIMA) to LAD - best patency (>90% at 10 years)
• Saphenous vein grafts - lower patency (~50% at 10 years)

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10. KILLIP CLASSIFICATION (Clinical severity post-MI)

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11. SPECIAL CONCEPTS

Myocardial Stunning

• Transient, reversible post-ischemic dysfunction persisting for hours to days after reperfusion
• Myocyte is alive but non-contractile due to persistent biochemical abnormalities
• Function recovers spontaneously with time

Myocardial Hibernation

• Chronic, persistent reduction in regional myocardial contractility due to chronic ischemia
• A protective "down-regulation" of metabolism to match reduced blood supply
• Reversible with revascularization - important concept for deciding CABG vs medical therapy
• Diagnosed by: viability studies (dobutamine stress echo, PET scan)

Ischemic Preconditioning

• Brief episodes of ischemia followed by reperfusion make the myocardium more resistant to a subsequent prolonged ischemic insult
• Mediated by adenosine, bradykinin, PKC, KATP channels
• Basis of "ischemic preconditioning" phenomenon and research into cardioprotective strategies

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12. PROGNOSIS AND MORTALITY

• Overall in-hospital mortality for MI: 7-8%
• STEMI mortality: ~10% in-hospital; one-third die out-of-hospital (mostly from VF within 1 hour)
• NSTEMI mortality: ~6% in-hospital; but cumulative 1-year mortality approaches STEMI
• Factors worsening prognosis:
  • Large infarct size
  • Reduced EF (<40%)
  • Cardiogenic shock
  • Advanced age, female sex (worse outcomes due to treatment delays)
  • Diabetes mellitus
  • Multivessel disease
  • VT/VF on presentation
  • Late presentation (>12 h without reperfusion)
• Mortality has fallen by 50% since 1963 - attributed to:
  • Smoking cessation, statin use, BP control
  • Aspirin, beta-blockers, ACE inhibitors
  • CCU-based monitoring for arrhythmia
  • Thrombolysis and primary PCI
  • Mechanical circulatory support devices

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Summary: Key Differences Table

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