Discuss the pathogenesis, classification, clinical features, investigations and management of acute coronary syndrome.

Definition and Classification

Acute coronary syndrome (ACS) is the spectrum of conditions caused by acute myocardial ischaemia, usually from rupture or erosion of an atherosclerotic plaque with superimposed thrombosis.

Unstable angina and NSTEMI together are termed NSTE-ACS, and are managed along a common pathway; STEMI is a separate emergency pathway centred on immediate reperfusion.

Pathogenesis

Atherosclerotic plaques with a large lipid core and a thin fibrous cap are vulnerable to rupture. Plaque rupture or erosion exposes thrombogenic material, triggering platelet adhesion, activation and aggregation, and activation of the coagulation cascade, producing thrombus. Vasoconstriction from released mediators worsens the obstruction.

Importantly, the culprit lesion is often NOT the most severe stenosis — a moderate but unstable plaque is more dangerous than a tight but stable one, which is why angiographic severity alone does not predict infarction.

Risk factors: non-modifiable — age, male sex, family history, South Asian ethnicity (which confers earlier and more severe disease); modifiable — smoking, hypertension, diabetes, dyslipidaemia, obesity, physical inactivity, stress, and diet.

Clinical Features

• Chest pain — retrosternal, crushing, heavy or constricting, radiating to the left arm, both arms, jaw, neck or interscapular region; lasting more than 20 minutes, unrelieved by rest or nitrates.
• Autonomic features — sweating (diaphoresis), nausea and vomiting; anxiety and a sense of impending doom.
• Breathlessness, palpitations, syncope.
• Examination is often unremarkable, which surprises students: look for pallor, sweating, tachycardia or bradycardia, hypotension, a fourth heart sound, a new murmur (mitral regurgitation from papillary muscle dysfunction — a serious sign), and signs of heart failure (Killip classification).

ATYPICAL AND SILENT PRESENTATIONS — critically important:

• Diabetics (autonomic neuropathy), the elderly, and women frequently present without chest pain — instead with breathlessness, fatigue, confusion, syncope, epigastric pain, vomiting or simply "not feeling well".
• Up to a third of infarcts are clinically silent and detected later on ECG.
• In India, inferior wall infarction presenting as epigastric pain and vomiting is commonly misdiagnosed as gastritis or food poisoning — an error that kills.

Investigations

1. ECG — within 10 minutes of first medical contact, and repeated

Evolution in STEMI: hyperacute T waves → ST elevation → pathological Q waves → T wave inversion → ST normalisation with persistent Q waves.

A serial ECG is essential — a single normal ECG never excludes ACS.

2. Cardiac biomarkers

• High-sensitivity cardiac troponin I or T — the biomarker of choice. Rises within 3–4 hours (detectable earlier with high-sensitivity assays), peaks at 24–48 hours, and remains elevated for up to 10–14 days.
• A rising and/or falling pattern on serial testing establishes acute myocardial injury — a single raised value does not.
• Troponin is raised in many non-ACS conditions — pulmonary embolism, sepsis, heart failure, myocarditis, renal failure, tachyarrhythmia, stroke — so it must be interpreted with the clinical picture and ECG.
• CK-MB — less specific; useful for detecting re-infarction because it normalises sooner.

3. Others: CBC, renal function and electrolytes, glucose and HbA1c, lipid profile (within 24 hours), coagulation profile, chest X-ray (heart failure, and to exclude aortic dissection and other causes of chest pain), and echocardiography for regional wall motion abnormality, ejection fraction and mechanical complications.

Management

IMMEDIATE MEASURES FOR ALL — "MONA" is a memory aid, but the order is wrong: antiplatelets come first

• Aspirin (chewed, loading dose) immediately — the single most cost-effective intervention.
• Second antiplatelet (P2Y12 inhibitor — ticagrelor, prasugrel or clopidogrel) as loading dose.
• Anticoagulation — low-molecular-weight heparin, unfractionated heparin or fondaparinux.
• Nitrates — sublingual then intravenous for ongoing pain. Contraindicated in right ventricular infarction, hypotension, and after phosphodiesterase-5 inhibitors (sildenafil).
• Oxygen ONLY if SpO2 < 90% — routine oxygen in the non-hypoxic patient is harmful, increasing infarct size through coronary vasoconstriction. This is a change from older teaching and is frequently examined.
• Morphine for pain not relieved by nitrates (with an antiemetic); note it delays antiplatelet absorption.
• Beta-blocker early unless contraindicated (heart failure, hypotension, bradycardia, heart block, asthma, cocaine use).
• High-intensity statin for all, started immediately regardless of cholesterol level.
• Continuous cardiac monitoring and defibrillator availability — ventricular fibrillation is commonest in the first hour.

Stemi — Reperfusion Is the Priority: "time Is Myocardium"

• PRIMARY PERCUTANEOUS CORONARY INTERVENTION (PCI) is the preferred strategy if it can be delivered within the recommended time from first medical contact.
• FIBRINOLYSIS (thrombolysis) where timely PCI is unavailable — a critical consideration across much of India. Agents: streptokinase, alteplase, tenecteplase. Give as early as possible; benefit is greatest within the first 2–3 hours and declines sharply thereafter.
• Absolute contraindications to thrombolysis: previous intracranial haemorrhage, ischaemic stroke within 6 months, known cerebral vascular malformation or malignancy, active bleeding, suspected aortic dissection, recent major trauma, surgery or head injury (within 3 weeks), and known bleeding disorder.
• Assess reperfusion at 60–90 minutes — resolution of ST elevation by more than 50%, relief of pain, and reperfusion arrhythmias. Failed thrombolysis requires rescue PCI.
• Pharmaco-invasive strategy — routine angiography 3–24 hours after successful thrombolysis — is the standard where primary PCI is not available, and is well suited to Indian hub-and-spoke networks.

Nste-acs — Risk Stratify, Then Revascularise

• Use the GRACE or TIMI score to determine risk and the timing of invasive management.
• Very high risk (haemodynamic instability, refractory angina, life-threatening arrhythmia, mechanical complication) — immediate angiography.
• High risk (rising troponin, dynamic ST/T changes, GRACE > 140) — early invasive strategy within 24 hours.
• Low risk — non-invasive testing and a selective invasive approach.
• FIBRINOLYSIS IS CONTRAINDICATED IN NSTE-ACS — it increases mortality. This is a classic examination point and a real clinical error.

Secondary prevention — begun before discharge, and lifelong

Add a mineralocorticoid antagonist for LV dysfunction with heart failure or diabetes, and assess for ICD if the ejection fraction remains low after optimal therapy.

Complications

• Arrhythmias — ventricular fibrillation (the commonest cause of pre-hospital death), VT, AF, heart block (especially with inferior infarction)
• Heart failure and cardiogenic shock
• Mechanical (typically days 3–7): papillary muscle rupture with acute mitral regurgitation, ventricular septal rupture, free wall rupture with tamponade — all present with sudden deterioration and a new murmur or shock, and require urgent echocardiography and surgery
• Pericarditis — early, and Dressler's syndrome (autoimmune, at 2–6 weeks)
• Left ventricular aneurysm (persistent ST elevation, heart failure, arrhythmia, mural thrombus) and systemic embolism
• Depression and anxiety — common, under-recognised, and affecting adherence