Acute Coronary Syndromes (STEMI, NSTEMI, UA)

Mechanistic categories (Fourth Universal Definition of Myocardial Infarction)

• Type 1 MI — atherothrombosis: plaque rupture or erosion with superimposed thrombus; the mechanism behind the great majority of stem presentations and the one that mandates antithrombotic therapy plus revascularization
• Type 2 MI — supply–demand mismatch: necrosis without acute plaque rupture, from tachyarrhythmia, severe anemia or GI bleed, sepsis, hypotension, hypertensive crisis, severe aortic stenosis, or hypoxemia; the treatment is the precipitant, not fibrinolysis
• Non-atherosclerotic coronary occlusion: spontaneous coronary artery dissection (young or peripartum women, fibromuscular dysplasia); coronary vasospasm (cocaine, methamphetamine, Prinzmetal/vasospastic angina); coronary embolism (atrial fibrillation, infective endocarditis, prosthetic valve, patent foramen ovale); arteritis (Kawasaki disease aneurysms, Takayasu); in-stent thrombosis after premature DAPT interruption
• MINOCA: MI with non-obstructive coronaries — consider plaque erosion, spasm, dissection, microvascular dysfunction, or thrombophilia when angiography looks clean

Modifiable risk factors (the ones examiners plant)

• Cigarette smoking: endothelial injury plus prothrombotic effect; the single most potent modifiable factor in young patients
• Dyslipidemia: elevated LDL-C drives plaque burden; the 2018 AHA/ACC cholesterol guideline also treats elevated Lp(a), triglycerides, and hs-CRP as risk-enhancing factors
• Diabetes mellitus, hypertension, obesity, physical inactivity, poor diet: additive metabolic and hemodynamic stress on the vessel wall; diabetic autonomic neuropathy also explains silent presentations
• Chronic kidney disease and chronic inflammatory disease: CKD, HIV, SLE, and rheumatoid arthritis accelerate atherosclerosis and are named risk enhancers by AHA/ACC
• Sympathomimetic use: cocaine produces vasospasm, hypertension, and platelet activation — suspect in a young patient with chest pain

Non-modifiable risk factors

• Age and male sex: risk rises steeply with age; women's risk climbs after menopause
• Family history of premature ASCVD: first-degree male relative before 55 or female before 65
• Genetic/ancestry factors: familial hypercholesterolemia, inherited elevated Lp(a), South Asian ancestry (an AHA/ACC risk enhancer)
• Adverse pregnancy history: preeclampsia and gestational diabetes mark long-term cardiovascular risk in women

• Atherosclerotic plaque rupture: Rupture of a vulnerable coronary plaque (typically with a thin fibrous cap) exposes the thrombogenic lipid-rich core to circulating blood, triggering the coagulation cascade and platelet aggregation
• Thrombus formation: Platelets adhere via von Willebrand factor and collagen exposure, aggregating through P2Y12 and glycoprotein IIb/IIIa receptors; simultaneously, tissue factor activates the extrinsic coagulation pathway, forming an occlusive or partially occlusive thrombus
• Myocardial ischemia and infarction: Acute reduction in coronary blood flow below critical threshold causes anaerobic metabolism, ATP depletion, cellular edema, and loss of membrane integrity; prolonged ischemia (typically >20-30 minutes) leads to irreversible necrosis progressing from subendocardium to epicardium
• STEMI vs. NSTEMI distinction: STEMI (ST-elevation MI) occurs with complete/near-complete coronary occlusion causing transmural infarction with ST-segment elevation on ECG; NSTEMI and UA result from partial occlusion or temporary thrombosis with subendocardial ischemia (no ST elevation), distinguished by presence (NSTEMI) or absence (UA) of myocardial necrosis markers
• Inflammatory cascade: Release of damage-associated molecular patterns (DAMPs) from ischemic myocardium triggers inflammatory cell infiltration, cytokine release, and reactive oxygen species generation, which if unchecked contributes to ventricular remodeling and heart failure

• Chest pain/discomfort: Classic presentation is substernal, crushing or pressure-like pain radiating to left arm, jaw, or shoulder; may be described as heaviness or "elephant on chest"; typically lasts >20 minutes and is unresponsive to rest or nitrates (unlike stable angina)
• Diaphoresis and autonomic symptoms: Profuse sweating, nausea, vomiting, and dyspnea often accompany chest pain; sympathetic activation causes anxiety, while parasympathetic activation causes bradycardia and hypotension
• Atypical presentations: Women, elderly patients, and diabetics frequently present with atypical symptoms including dyspnea without chest pain, fatigue, syncope, or epigastric discomfort; diabetics may have silent ischemia due to autonomic neuropathy
• Symptom-free periods in UA: Unstable angina presents as new-onset angina, rapidly progressive angina (crescendo pattern), or angina at rest; symptoms are more frequent and severe than baseline stable angina but lack elevated biomarkers
• Physical examination findings: Tachycardia, hypertension, hypotension, hypoxia, pulmonary crackles (signs of acute heart failure), new murmur (papillary muscle rupture), pericardial friction rub (pericarditis), or signs of cardiogenic shock in large anterior MIs
• Critical pearl: Absence of symptoms does NOT exclude ACS; serial ECGs and troponins are mandatory in all suspected cases

• 12-lead electrocardiogram (ECG): Most important initial test; must be performed within 10 minutes of presentation. STEMI shows ST-segment elevation ≥2 mm in contiguous leads (≥1 mm in aVR/V1); NSTEMI/UA show ST-segment depression, T-wave inversion, or normal ECG (up to 50% of NSTEMIs have initially normal ECG). Reciprocal ST depression and peaked T waves are supportive findings. Serial ECGs increase sensitivity
• Cardiac biomarkers (troponin): High-sensitivity troponin I or T is the gold standard; detectable within 2-4 hours of symptom onset, peaks at 24-72 hours. NSTEMI shows elevated troponin; UA shows normal troponin despite ischemic ECG changes or symptoms. Serial troponin (baseline, 3 hours, 6 hours) improves diagnostic accuracy; single negative high-sensitivity troponin at presentation does NOT rule out early MI
• Coronary angiography: Gold standard for defining coronary anatomy and identifying culprit lesion. STEMI requires emergent percutaneous coronary intervention (PCI) within 90 minutes (or fibrinolysis within 30 minutes if PCI unavailable); NSTEMI/UA with high-risk features require angiography within 24 hours
• Risk stratification tools: TIMI risk score (for NSTEMI/UA) incorporates age, cardiac risk factors, prior CAD, ST changes, elevated troponin, and aspirin use to predict 14-day adverse events; GRACE score provides mortality prediction and guides management intensity
• Additional testing: Chest X-ray (pulmonary edema, alternative diagnoses), echocardiography (wall motion abnormalities, complications, ejection fraction), and troponin-negative ACS mimics (pulmonary embolism, aortic dissection, myocarditis, sepsis)

Immediate Management (All ACS)

• Dual antiplatelet therapy (DAPT): Aspirin 325 mg loading dose, then 81 mg daily indefinitely; P2Y12 inhibitor (clopidogrel 600 mg load, ticagrelor 180 mg load, or prasugrel 60 mg load) continued for 12 months post-ACS
• Anticoagulation: Unfractionated heparin (UFH) bolus 60-70 units/kg IV, then 12-15 units/kg/hour infusion (preferred for STEMI patients who may need urgent surgery); enoxaparin or fondaparinux alternative in NSTEMI
• Beta-blockers: Metoprolol 25-50 mg PO BID or esmolol IV in acute setting; reduces heart rate, blood pressure, and myocardial oxygen demand; reduces reinfarction risk and mortality
• ACE inhibitors/ARBs: Lisinopril 5-10 mg daily or losartan 50 mg daily; started acutely (especially anterior MI, reduced EF, or diabetes); provide cardioprotection and reduce remodeling
• High-intensity statins: Atorvastatin 80 mg daily or rosuvastatin 20-40 mg daily; acute loading dose recommended regardless of baseline lipids; pleiotropic anti-inflammatory effects

STEMI-Specific Therapy

• Percutaneous coronary intervention (PCI): Primary PCI is the preferred reperfusion strategy (door-to-balloon time goal ≤90 minutes) with stent placement (bare-metal stent in acute setting, drug-eluting stent acceptable if bleeding risk low); achieves superior outcomes vs. fibrinolysis
• Fibrinolytic therapy: Alteplase, reteplase, or tenecteplase IV if PCI unavailable within 120 minutes; door-to-needle time goal ≤30 minutes; greatest benefit if given within 12 hours of symptom onset (most benefit within 6 hours). Contraindicated in active bleeding, recent stroke, intracranial pathology, or severe hypertension

NSTEMI/UA-Specific Approach

• Risk stratification determines timing: High-risk features (elevated troponin, dynamic ECG changes, hemodynamic instability, heart failure, arrhythmias) warrant early invasive strategy with angiography within 24 hours (preferably 6-12 hours); low-risk patients may undergo ischemia-guided approach with angiography only if recurrent symptoms or positive stress test
• Additional anticoagulation options: Glycoprotein IIb

Arrhythmic (earliest and most lethal)

• Ventricular fibrillation / pulseless VT: reentry around ischemic border zones, usually within the first 48 hours; pulseless patient with a shockable rhythm — immediate defibrillation per AHA ACLS, not antiarrhythmic drugs first. Emergency.
• Bradyarrhythmias and AV block: inferior MI occludes the RCA, which supplies the AV node in most people — sinus bradycardia or Mobitz I/complete block that is often atropine-responsive; anterior MI producing Mobitz II or new bundle branch block reflects extensive septal necrosis and predicts need for pacing
• Accelerated idioventricular rhythm: classic reperfusion arrhythmia after PCI or fibrinolysis; usually benign and self-limited

Hemodynamic

• Cardiogenic shock: loss of >40% of LV mass; cold extremities, oliguria, elevated lactate — emergency requiring urgent revascularization
• Right ventricular infarction: inferior/posterior STEMI with hypotension, elevated JVP, and clear lung fields; preload-dependent, so nitrates and diuretics cause profound hypotension — give fluids
• Acute heart failure and adverse remodeling: neurohormonal activation and infarct expansion; drives long-term HFrEF therapy

Mechanical (days 3–14, post-necrotic softening — all emergencies)

• Papillary muscle rupture: posteromedial muscle has single-vessel (PDA) supply; acute severe mitral regurgitation with flash pulmonary edema and a new soft systolic murmur
• Ventricular septal rupture: harsh holosystolic murmur with thrill, new left-to-right shunt, shock
• Free wall rupture: sudden hypotension, JVD, pulsus paradoxus, PEA arrest from tamponade
• LV aneurysm / mural thrombus: dyskinetic scar with persistent ST elevation and Q waves weeks later; stasis thrombus can embolize to brain

Inflammatory

• Early peri-infarct pericarditis (days 1–3, friction rub) versus Dressler syndrome (autoimmune, weeks later, fever plus effusion); treat with aspirin or colchicine — avoid other NSAIDs and steroids, which impair healing

Treatment-related

• Bleeding: fibrinolytics carry intracranial hemorrhage risk (any new neurologic deficit demands stat head CT and drug cessation — emergency); femoral access can cause retroperitoneal hematoma with flank pain and unexplained hypotension
• Stent thrombosis: abrupt re-elevation of ST segments after premature DAPT interruption
• Contrast-associated AKI, cholesterol embolization, and heparin-induced thrombocytopenia: platelet drop after day 4–5 of heparin with new thrombosis

• ECG in 10 minutes is the single best next step in any suspected ACS, and chewed non-enteric aspirin is the first drug — both precede troponin results, per ACC/AHA ACS guidance. Do not wait for biomarkers to activate the cath lab in STEMI
• ST depression in V1–V3 with tall R waves = posterior STEMI, not "NSTEMI"; it is a left circumflex occlusion and a reperfusion indication. Obtain posterior leads V7–V9. This is the most common missed-STEMI distractor
• ST elevation in aVR with diffuse ST depression suggests left main or proximal LAD occlusion — high mortality, urgent angiography
• Inferior MI with hypotension after nitroglycerin = RV infarct; the tested answer is IV fluids, and nitrates/morphine/diuretics are the wrong choices. Confirm with ST elevation in lead III > II and V1
• Beta blockers are withheld, not given, in cardiogenic shock, acute decompensated heart failure, bradycardia/high-grade block, and cocaine-associated chest pain (unopposed alpha vasoconstriction) — use benzodiazepines and nitrates for cocaine
• New murmur plus shock on day 3–5 → get an urgent echocardiogram; holosystolic murmur with thrill favors septal rupture, flash pulmonary edema with a soft murmur favors papillary muscle rupture
• Troponin stays elevated up to 7–10 days, so suspected reinfarction within that window is judged by a rising trend on serial high-sensitivity troponin (CK-MB, which normalizes in 2–3 days, is the classic older answer)
• Persistent ST elevation with Q waves weeks after MI = LV aneurysm; think mural thrombus and embolic stroke, not reocclusion
• All ACS patients leave on the same core regimen: aspirin indefinitely, a P2Y12 inhibitor for about 12 months, a high-intensity statin, a beta blocker, and an ACEI/ARB when EF is reduced, diabetes, or anterior MI; if EF remains ≤40%, layer on the four HFrEF classes — ARNI (or ACEI/ARB), beta blocker, MRA, and SGLT2 inhibitor — plus cardiac rehabilitation