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ISCHEMIC HEART DISEASE: A GOLD-MEDALIST'S COMPREHENSIVE CLINICAL NOTE

Stable Angina | Unstable Angina | NSTEMI | STEMI

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PART 1 - THE SPECTRUM OF ISCHEMIC HEART DISEASE

STABLE ANGINA ──► UNSTABLE ANGINA ──► NSTEMI ──► STEMI
  Transient ischemia   Plaque rupture/   Plaque rupture   Complete occlusion
  no necrosis          non-occlusive Tx  myocyte necrosis transmural necrosis
                       no necrosis       (+troponin)      (+troponin + ST↑)

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PART 2 - NORMAL CORONARY PHYSIOLOGY

• Heart rate (most important - doubles O2 demand)
• Afterload (wall stress = pressure × radius / 2 × thickness, LaPlace)
• Contractility (inotropy)
• Preload (wall tension at end-diastole)

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PART 3 - PATHOLOGY OF CORONARY ARTERY DISEASE

3.1 Atherosclerosis: The Substrate

• Large lipid-rich necrotic core (>40% of plaque volume)
• Thin fibrous cap (<65 μm, normal >200 μm)
• Rich inflammatory infiltrate at shoulders - macrophages elaborate metalloproteinases (MMPs) that degrade collagen
• Sparse smooth muscle cells - less collagen synthesis
• Neovascularisation within the plaque - intraplaque haemorrhage predisposes to rupture

3.2 Plaque Disruption: Two Mechanisms

1. Subendothelial collagen and necrotic plaque contents exposed
2. Platelets adhere via GPIb-vWF and GPVI-collagen interactions → activation
3. Activated platelets release TXA2, ADP, serotonin → further platelet aggregation + vasospasm
4. Tissue factor activates extrinsic coagulation → thrombin generation → fibrin mesh
5. Thrombus grows → partial or complete occlusion
6. Distal embolisation of platelet-fibrin fragments → microvascular obstruction

3.3 Temporal Morphology of Myocardial Infarction

• Cessation of aerobic metabolism: seconds
• Loss of contractility: <2 minutes
• ATP falls to 50%: 10 minutes
• Irreversible cell injury: 20-40 minutes (the "golden window")
• Microvascular injury: >1 hour

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PART 4 - STABLE ANGINA (CHRONIC CORONARY SYNDROME)

4.1 Definition and Epidemiology

4.2 Pathophysiology

4.3 Canadian Cardiovascular Society (CCS) Classification

4.4 Clinical Features

1. Substernal chest discomfort - pressure, tightness, heaviness, squeezing - never sharp/stabbing
2. Precipitated by exertion or emotional stress
3. Relieved within 2-5 minutes by rest or sublingual nitroglycerine

4.5 Investigations

• Positive: ≥1mm horizontal/downsloping ST depression in 2 contiguous leads
• High-risk features: early ST changes (stage 1), widespread changes, hypotension with exercise, angina at low workload, failure to complete stage 2

4.6 Management of Stable Angina

• Smoking cessation (halves MI risk in first year)
• Statin therapy - target LDL <1.4 mmol/L (<55 mg/dL) for very high cardiovascular risk (2024 ESC Dyslipidaemia Guidelines)
• Blood pressure control: target <130/80 mmHg
• Diabetes control: HbA1c target <53 mmol/mol
• Weight reduction, exercise, Mediterranean diet

• Sublingual Nitroglycerine (GTN): 0.3-0.6 mg sublingual or spray for acute attacks. Onset 2-3 min, duration 30 min. Mechanism: venodilation → reduced preload → reduced wall tension → reduced MVO2; also coronary vasodilation.
• Beta-blockers: Metoprolol succinate 25-200 mg OD or bisoprolol 2.5-10 mg OD. Reduce HR, contractility, afterload at rest and exercise. Target resting HR 55-60 bpm. First-line for all stable angina. Reduce sudden cardiac death. Contraindications: severe asthma, 2nd/3rd degree AV block, cardiogenic shock.

• Calcium Channel Blockers (CCBs): Amlodipine 5-10 mg OD (dihydropyridine) for coronary vasodilation; diltiazem 60-120 mg TDS or verapamil (non-DHP) for rate control + vasodilation. Avoid short-acting nifedipine (reflex tachycardia increases MVO2). Verapamil/diltiazem contraindicated with beta-blockers (synergistic AV block and bradycardia risk).
• Long-acting nitrates: Isosorbide mononitrate (ISMN) 25-120 mg OD. Nitrate tolerance avoided by 8-12 hour nitrate-free window.
• Ivabradine: Sinus node If channel blocker. Heart rate reduction without negative inotropy. Use if beta-blocker contraindicated or HR >70 bpm despite beta-blocker. NOT effective in AF (relies on sinus node).
• Ranolazine: Late sodium current inhibitor; reduces calcium overload. Add-on therapy; does not reduce HR or BP.
• Nicorandil: K-ATP channel opener + nitrate effect. UK/European use. Angina relief + coronary vasodilation.
• Trimetazidine: Metabolic modulator (shifts myocardial substrate from fatty acid to glucose oxidation). Used in Europe/Asia. Restricted in some countries (Parkinson's disease risk).

• Aspirin 75-100 mg OD indefinitely - mandatory for all patients with confirmed CAD (Class I).
• Clopidogrel 75 mg OD: alternative if aspirin-intolerant.

• PCI (Percutaneous Coronary Intervention): For symptom relief refractory to optimal medical therapy. Does NOT improve survival in stable disease without evidence of significant ischaemia (COURAGE, ORBITA trials). FFR-guided PCI improves outcomes (FAME 2).
• CABG (Coronary Artery Bypass Grafting): Survival benefit over PCI in: left main disease, 3-vessel disease with LV dysfunction (EF <35%), diabetes with multivessel disease, complex anatomy (high SYNTAX score >22). Left internal mammary artery (LIMA) to LAD is the gold standard graft - 90% patency at 10 years vs 50% for saphenous vein graft.

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PART 5 - UNSTABLE ANGINA (UA)

5.1 Definition

1. New-onset angina: At least CCS Class II, onset within 2 months
2. Crescendo/accelerating angina: Previously stable angina becoming more frequent, longer in duration, or provoked by lesser exertion (worsening by at least 1 CCS class to at least Class III)
3. Rest angina: Angina at rest, lasting >20 minutes, occurring within 1 week of presentation

5.2 Pathophysiology

• Episodic complete occlusion (transient)
• Distal microembolisation of platelet-fibrin aggregates
• Coronary vasospasm at the disrupted site

5.3 TIMI Risk Score for NSTE-ACS (Antman et al.)

1. Age ≥65 years
2. ≥3 CAD risk factors (family history, hypertension, hypercholesterolaemia, diabetes, smoking)
3. Known CAD (stenosis ≥50%)
4. ST deviation ≥0.5 mm on presenting ECG
5. ≥2 anginal episodes in prior 24 hours
6. Use of aspirin in prior 7 days (marker of aspirin-refractory disease)
7. Elevated serum cardiac markers

• Score 0-1: 5% | Score 2: 8% | Score 3: 13% | Score 4: 20% | Score 5: 26% | Score 6-7: 41%

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PART 6 - NSTEMI

6.1 Definition

• Symptoms of myocardial ischaemia, AND
• Troponin elevated above 99th percentile URL with rise/fall pattern, AND
• No persistent ST elevation (≥20 minutes)

6.2 ECG Changes in NSTEMI

• ST depression: Horizontal (≥0.05 mV) or downsloping (≥0.1 mV) in ≥2 contiguous leads - most specific for ischaemia
• T-wave inversion: Symmetric deep T-wave inversions (Wellens syndrome types A & B = critical LAD proximal stenosis - do NOT exercise test!)
• Transient ST elevation: May occur during ischaemic episodes
• Normal ECG: In up to 6% of confirmed NSTEMI (does NOT exclude diagnosis)
• New LBBB: Does not always indicate STEMI (ESC 2023 modification of Sgarbossa criteria)

6.3 Biomarkers

• 0h hsTn below the detection limit AND very low GRACE score → rule out at presentation
• 0h hsTn above 99th percentile URL OR any absolute change at 1h ≥5 ng/L (hsTnI) → rule in NSTEMI
• If indeterminate at 1h → measure at 3h

• CK-MB: rises 3-12h, peaks 18-24h, normalises 36-72h. Useful for reinfarction detection.
• LDH: rises 24-48h, peaks 3-6 days, persists 8-14 days. LDH1>LDH2 (flip) = MI.
• Myoglobin: earliest (1-4h) but non-specific; now largely obsolete.
• BNP/NT-proBNP: elevated with LV dysfunction; prognostic marker.

6.4 Causes of Troponin Elevation BEYOND Type 1 MI

6.5 NSTEMI Management: ESC 2023 Algorithm

Initial General Measures

• IV access, oxygen only if SpO2 <90% (hyperoxia is harmful in uncomplicated MI)
• 12-lead ECG within 10 minutes of presentation, repeated if initial non-diagnostic
• hsTroponin at 0h and 1h (ESC algorithm) or 0h and 3h
• Continuous cardiac monitoring
• Bloods: FBC, U&E, LFTs, coagulation, lipids, glucose/HbA1c, TFTs

Anti-ischaemic Therapy

• Nitrates: SL GTN for chest pain; IV infusion for persistent pain or hypertension. Avoid with hypotension, RV infarct, PDE-5 inhibitor use (within 24h sildenafil/vardenafil, 48h tadalafil).
• Beta-blockers: Oral metoprolol or bisoprolol unless haemodynamic contraindication. Target HR 55-60 bpm. IV metoprolol 5mg (up to 3 doses) if tachycardia or hypertension without HF.
• Morphine/Opioids: For refractory pain. CAUTION: may delay P2Y12 inhibitor absorption; use fentanyl IN preference if needed.
• Calcium Channel Blockers: If beta-blocker contraindicated or vasospastic component.

Antiplatelet Therapy (Dual Antiplatelet Therapy - DAPT)

• Aspirin: 150-300 mg loading dose IMMEDIATELY (chewed for faster absorption), then 75-100 mg OD indefinitely.
• P2Y12 inhibitor (in addition to aspirin):
  • Ticagrelor 180 mg load, then 90 mg BD (preferred - reversible, fast onset, does not require hepatic activation; PLATO trial: superior to clopidogrel in ACS)
  • Prasugrel 60 mg load, then 10 mg OD (if PCI planned and patient not on anticoagulants; TRITON-TIMI 38 trial; CONTRAINDICATED in prior stroke/TIA, age >75, weight <60 kg)
  • Clopidogrel 300-600 mg load, then 75 mg OD (if ticagrelor/prasugrel unavailable, contraindicated, or patient requires OAC - CURE trial)

Anticoagulant Therapy

• Unfractionated Heparin (UFH): 60-70 U/kg IV bolus (max 5000 U) then infusion 12-15 U/kg/h (max 1000 U/h). Monitor aPTT 1.5-2.5x control. Preferred for planned PCI (reversible with protamine).
• Low Molecular Weight Heparin (LMWH): Enoxaparin 1 mg/kg SC BD (fondaparinux preferred if no immediate PCI). Predictable pharmacokinetics; no monitoring required.
• Fondaparinux 2.5 mg SC OD: ESC preferred anticoagulant for NSTEMI when immediate invasive strategy not planned (superior to enoxaparin in OASIS-5: less bleeding, similar efficacy). Must add UFH at time of PCI.
• Bivalirudin: Direct thrombin inhibitor. Alternative to UFH + GPI during PCI; similar efficacy with less bleeding (HORIZONS-AMI, EUROMAX). ESC 2023: acceptable.
• Anticoagulation continues until revascularisation or discharge (whichever first).

Risk Stratification and Invasive Strategy (ESC 2023)

Statin and Other Secondary Prevention

• High-intensity statin immediately (atorvastatin 40-80 mg or rosuvastatin 20-40 mg) regardless of baseline LDL. LDL target <1.4 mmol/L (<55 mg/dL) with ≥50% reduction from baseline.
• ACE inhibitor/ARB: Start within 24h if EF <40%, HF, hypertension, or diabetes (reduces LV remodelling).
• Aldosterone antagonist (eplerenone/spironolactone): If EF <40% and HF or diabetes (EPHESUS trial).
• Beta-blocker: Long-term for all post-MI with reduced EF; evidence less clear for preserved EF post-MI.
• Colchicine: NEW - ESC 2023 considers colchicine 0.5 mg OD for secondary prevention in high-risk patients (LoDoCo2, COLCOT trials). Class IIb.

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PART 7 - STEMI

7.1 Definition and ECG Criteria

• All leads except V2-V3: ≥0.1 mV (1 mm)
• V2-V3 in men ≥40 years: ≥0.2 mV (2 mm)
• V2-V3 in men <40 years: ≥0.25 mV (2.5 mm)
• V2-V3 in women: ≥0.15 mV (1.5 mm)

• New LBBB (with Sgarbossa criteria concordance)
• De Winter pattern (upsloping ST depression with ST elevation in aVR = proximal LAD occlusion)
• Wellens syndrome (critical LAD stenosis - NOT STEMI but urgent)
• Posterior STEMI: ST depression in V1-V3 with tall R waves (use posterior leads V7-V9)
• RV STEMI: ST elevation in V4R ≥1mm (seen with inferior STEMI; complicates ~40% of inferior MI)

7.2 Pathophysiology of STEMI

7.3 Clinical Presentation

• Severe crushing/squeezing chest pain, typically lasting >20-30 minutes, NOT relieved by rest or GTN
• Radiation to left arm, jaw, neck, interscapular area
• Associated: diaphoresis, nausea/vomiting, dyspnoea, profound malaise ("sense of impending doom")
• "Silent MI" in ~20-25% (especially elderly, diabetics, women)

• Anxious, pale, sweating, tachycardia or bradycardia (inferior MI → vagal tone)
• S4 gallop (universal in STEMI)
• Soft S1 (poor LV function)
• New MR murmur (papillary muscle dysfunction/rupture)
• Signs of left HF: S3, pulmonary crackles, raised JVP
• Signs of cardiogenic shock: hypotension, cold peripheries, oliguria, altered GCS

7.4 Immediate Management of STEMI - "TIME IS MUSCLE"

Pre-Hospital / Emergency

• Call 999/emergency services; activate STEMI team pre-arrival
• ECG within 10 minutes of first medical contact - transmitted to receiving centre
• Aspirin 300 mg chewed immediately
• P2Y12 inhibitor loading pre-hospital: ticagrelor 180 mg (preferred) or prasugrel 60 mg (if PCI planned, no prior stroke/TIA)
• Supplemental oxygen if SpO2 <90%
• IV access; basic bloods
• SL/IV nitrates for pain (avoid if hypotension or inferior + RV infarct)
• Morphine/fentanyl for refractory pain
• Anticoagulation: UFH 60-70 U/kg IV or enoxaparin 0.5 mg/kg IV if PCI centre

Reperfusion Strategy

• FMC (first medical contact) to ECG diagnosis: ≤10 min
• FMC to primary PCI (balloon): ≤90 min (≤60 min if door-to-balloon at PCI centre)
• FMC to fibrinolysis: ≤30 min (if PCI not available within 120 min)
• Total ischaemic time target: ≤120 min from symptom onset to reperfusion

• Available within 120 minutes of FMC (ESC) / 90 minutes (ACC/AHA)
• Fibrinolysis is contraindicated
• Cardiogenic shock or acute severe HF
• Failed fibrinolysis (rescue PCI)
• Symptom onset 12-24h with ongoing symptoms

• Superior TIMI 3 flow restoration (90-95% vs 50-60%)
• 40% lower mortality compared to historical controls
• Less reinfarction
• No risk of intracranial haemorrhage
• Direct assessment of coronary anatomy

• Prior intracranial haemorrhage
• Ischaemic stroke within 6 months
• CNS neoplasm or AVM
• Major trauma/surgery/head injury within 3 weeks
• GI bleeding within 1 month
• Aortic dissection
• Non-compressible vascular punctures within 24h

• Tenecteplase (TNKase): Weight-based single IV bolus; most convenient; ASSENT-2 trial.
• Alteplase (tPA): Weight-based, 90-min protocol. 15mg IV bolus, then 0.75 mg/kg over 30 min (max 50 mg), then 0.5 mg/kg over 60 min (max 35 mg).
• Reteplase (rPA): Two boluses 30 min apart.
• Streptokinase: Non-fibrin-specific; no longer preferred; anaphylaxis risk; cannot be given a second time within 5 years.

1. Chest pain relief
2. ≥50% reduction in ST elevation
3. Reperfusion arrhythmias (accelerated idioventricular rhythm - AIVR)
4. Peak troponin/CK-MB within 12 hours (early washout)

Multivessel Disease in STEMI

• Only the culprit vessel should be treated at the time of primary PCI (unless other vessels are severely diseased and there is haemodynamic compromise)
• Complete revascularisation of non-culprit vessels should be performed at a staged procedure before hospital discharge or within 45 days (COMPLETE trial, ESC 2023, Class I)

Technical Aspects of Primary PCI

• Radial access preferred over femoral (lower bleeding, lower mortality in STEMI; MATRIX trial)
• Drug-eluting stents (DES) preferred over bare metal stents (BMS) - lower restenosis rate
• Aspiration thrombectomy: NOT routinely recommended (TASTE, TOTAL trials showed no benefit; possible harm from stroke)
• GPIIb/IIIa inhibitors (tirofiban, abciximab): Bailout only for large thrombus burden; not routine (ESC 2023, Class IIb)
• Intracoronary thrombus burden: Use of imaging (IVUS/OCT) can guide stent sizing

7.5 STEMI-Specific Pharmacology

Anti-Platelet (DAPT as above for NSTEMI)

• Aspirin 300 mg load → 75-100 mg OD lifelong
• Ticagrelor 180 mg → 90 mg BD OR prasugrel 60 mg → 10 mg OD for 12 months
• In patients with prior stroke/TIA or on OAC: clopidogrel preferred

Anticoagulation during primary PCI

• UFH: 70-100 U/kg IV bolus (if no GPIIb/IIIa) or 50-60 U/kg (with GPIIb/IIIa). Target ACT 250-350s.
• Bivalirudin: 0.75 mg/kg IV bolus then 1.75 mg/kg/h during PCI. Preferred if high bleeding risk.
• Anticoagulation can be stopped after uncomplicated PCI (unlike NSTEMI where it continues).

Post-STEMI Medications

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PART 8 - COMPLICATIONS OF MI

8.1 Causes of Death After MI (Guyton & Hall, Ch. 21)

1. Decreased cardiac output → Cardiogenic shock
2. Pulmonary oedema → Especially with delayed fluid retention (days post-MI)
3. Ventricular fibrillation → Most common cause of pre-hospital death; 2 peaks of vulnerability (within 10 min and 1-2h post-MI)
4. Cardiac rupture → Rare; peaks at 3-7 days

8.2 Mechanical Complications (Peak 2-7 days post-STEMI)

8.3 Arrhythmic Complications

• VF/VT: Most common cause of early death. Immediate defibrillation. Prophylactic beta-blockers reduce risk. ICD indicated if EF <35% at 40+ days post-MI despite optimal medical therapy.
• Sinus bradycardia / AV block: Common with inferior MI (vagal tone, AV node supplied by RCA). Usually transient; respond to atropine. High-degree AV block with anterior MI is more ominous (infranodal block) and may require permanent pacemaker.
• AIVR (Accelerated Idioventricular Rhythm): HR 60-120 bpm, wide QRS; reperfusion arrhythmia, benign, no treatment.
• AF: Common (~10-20% of STEMI); treat rate; anticoagulate if CHA2DS2-VASc ≥2.
• RBBB/LBBB: New bundle branch block suggests large territory infarcted; higher risk of complete AV block.

8.4 Pericardial Complications

• Acute pericarditis (Epistenocardiac): Within 24-72h; pleuritic chest pain, pericardial friction rub, saddle-shaped ST elevation on ECG. Treat with aspirin (NSAIDs avoid for 4 weeks - impair scar healing), colchicine.
• Dressler Syndrome: Autoimmune pericarditis 1-8 weeks post-MI. Fever, pleuritis, pericarditis, elevated ESR/CRP. Treat with aspirin + colchicine ± short course prednisolone.

8.5 Cardiogenic Shock

1. Immediate reperfusion (emergency PCI)
2. Inotropes: Dobutamine (beta-1 agonist; increases contractility without major vasoconstriction); Noradrenaline if profound hypotension
3. Intra-Aortic Balloon Pump (IABP): Provides diastolic augmentation + systolic unloading. ESC 2023: not routinely recommended (IABP-SHOCK II trial: no survival benefit) but considered in selected cases.
4. Mechanical circulatory support: Impella (microaxial flow pump), VA-ECMO for refractory cardiogenic shock (increasing evidence; ESC 2023 Class IIb)
5. Emergency CABG if anatomy unfavourable for PCI

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PART 9 - SECONDARY PREVENTION AND LONG-TERM FOLLOW-UP

9.1 The "ABCDE" of Post-ACS Care

• A = Antiplatelet + ACE-inhibitor + Aldosterone antagonist
• B = Beta-blocker + Blood pressure control (<130/80 mmHg)
• C = Cholesterol (LDL <1.4 mmol/L) + Cessation of smoking
• D = Diabetes management (HbA1c <53 mmol/mol; SGLT2i/GLP-1 RA for those with DM and CVD)
• E = Exercise (cardiac rehabilitation) + Education

9.2 Cardiac Rehabilitation

• All ACS patients should be enrolled in structured cardiac rehabilitation (Class I, ESC 2023)
• Phase I: In-hospital; early mobilisation
• Phase II: Outpatient structured exercise programme (8-12 weeks)
• Phase III: Long-term maintenance
• Reduces mortality by ~25%, readmissions, anxiety, depression

9.3 Specific Long-Term Therapies

9.4 Device Therapy

• ICD implantation: Indicated if EF ≤35% at ≥40 days post-MI on optimal medical therapy (OMT). Primary prevention of sudden cardiac death.
• CRT (Cardiac Resynchronisation Therapy): If EF ≤35% + LBBB + QRS ≥130ms on OMT; improves symptoms and mortality.
• Follow-up echo at 6-12 weeks: To reassess EF after optimal medical therapy; guides device decisions.

9.5 Follow-Up Schedule

9.6 Return to Activities

• Driving: DVLA (UK) - do not drive for 4 weeks after MI; 1 week if successful PCI (for Group 1 licence). Group 2 (HGV/bus): 6 weeks post-MI with satisfactory stress test.
• Sexual activity: Can resume at 4-6 weeks if can climb two flights of stairs without symptoms. PDE-5 inhibitors (sildenafil): do NOT use with nitrates; can use after 4-6 weeks if no other contraindication.
• Return to work: 4-6 weeks for desk jobs; 6-12 weeks for physical labour.
• Flying: Generally safe after 4-6 weeks for uncomplicated MI.

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PART 10 - KEY EXAMINATION POINTS AND MNEMONICS

The ACS Spectrum at a Glance

Mnemonics

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RECENT GUIDELINE UPDATES TO KNOW (2023-2025)

1. 2023 ESC ACS Guidelines (Byrne RA et al.) - first unified guideline for the entire ACS spectrum. Key updates:
   • Colchicine added for secondary prevention (IIb)
   • DAPT de-escalation before 30 days NOT recommended
   • Complete revascularisation of non-culprit vessels before discharge (Class I, COMPLETE trial)
   • hsTn 0h/1h rule-in/rule-out algorithm formalised
   • P2Y12 monotherapy as alternative to long-term aspirin (IIb)
   • After DAPT + anticoagulation for 6 months → anticoagulation alone acceptable (IIb)
2. 2024 ESC Chronic Coronary Syndromes Guidelines - CTCA as first-line investigation for stable chest pain in intermediate probability patients.
3. 2025 ACC/AHA ACS Guidelines (PMID: 40013746, Rao SV et al., J Am Coll Cardiol 2025; PMID: 40014670, Circulation 2025): Updated US guidelines now mirror ESC in addressing the full ACS spectrum. Key points:
   • Complete revascularisation endorsed
   • Radial access preferred
   • hsTn-based rapid rule-out algorithms endorsed
4. PCSK9 inhibitors post-ACS: Immediate initiation in hospital (within first 4 weeks of ACS) is now recommended if LDL not at target on statin - do not wait for lipid reassessment.

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