Acute Coronary Syndromes (STEMI, NSTEMI, Unstable Angina)

Acute coronary syndromes originate from abrupt destabilization of a vulnerable coronary atherosclerotic plaque characterized by a thin fibrous cap (<65 microns), a large lipid-rich necrotic core, and dense macrophage metalloproteinase infiltration. Exposure of subendothelial collagen and tissue factor triggers platelet adhesion via GpIb to von Willebrand factor, platelet activation (ADP and thromboxane A2 release), and aggregation via GpIIb/IIIa cross-linking fibrinogen. A Type 1 MI reflects primary coronary atherothrombosis (plaque rupture or erosion), whereas a Type 2 MI results from myocardial oxygen supply-demand mismatch without acute plaque rupture (such as severe sepsis, tachyarrhythmia, gastrointestinal hemorrhage, or hypertensive crisis) and is managed by correcting the underlying stressor rather than emergent heparin/thrombolysis.

High-sensitivity cardiac troponin I and T (hs-cTnI / hs-cTnT) are the gold-standard biomarkers of myocardial necrosis, rising within 2 to 3 hours of symptom onset, peaking at 12 to 24 hours, and remaining elevated for 7 to 14 days. Because troponin remains elevated for up to two weeks, recurrent chest pain occurring 3 to 5 days after an initial MI is evaluated with serial troponin measurements looking for a >20% dynamic rise (or serial CK-MB, which rises at 4–6 hours, peaks at 24 hours, and normalizes within 48 to 72 hours) to diagnose acute reinfarction or stent thrombosis.

Localizing the culprit coronary vessel from a 12-lead ECG predicts downstream mechanical and electrical complications: V1–V2 (anteroseptal) and V3–V4 (anterior) reflect occlusion of the left anterior descending (LAD) artery, supplying the anterior two-thirds of the interventricular septum, bundle branches (risking Mobitz II or complete heart block), and anterior left ventricular wall. I, aVL, V5–V6 (lateral) reflect the left circumflex (LCx) artery or diagonal branches of the LAD. II, III, and aVF (inferior) reflect the right coronary artery (RCA) in 85% of patients (right-dominant circulation) or the LCx in 15%, supplying the sinoatrial and atrioventricular nodes via the nodal branches and the posteromedial papillary muscle via the posterior descending artery (PDA).

Roughly 40% of inferior STEMIs (II, III, aVF) involve proximal RCA occlusion extending into the right ventricular marginal branches, producing Right Ventricular Infarction. Patients present with the classic triad of hypotension, elevated jugular venous pressure (Kussmaul sign), and clear lung fields, confirmed by ST elevation in right-sided precordial lead V4R. Because the ischemic right ventricle is exquisitely preload-dependent, nitrates, morphine, and diuretics are strictly contraindicated, and first-line treatment is isotonic intravenous crystalloid bolus resuscitation. Conversely, tall R waves (R/S ratio >1) with horizontal ST depressions and upright T waves in V1–V3 represent the reciprocal mirror image of a true posterior STEMI (PDA/LCx occlusion), confirmed by ST elevation in posterior leads V7–V9.

In STEMI, emergent Primary Percutaneous Coronary Intervention (PCI) is superior to fibrinolysis and must be achieved within a first-medical-contact-to-device time of <=90 minutes at a PCI-capable center or <=120 minutes if interhospital transfer is required. If PCI cannot be performed within 120 minutes and symptoms began within 12 hours, administer systemic fibrinolysis (tenecteplase or alteplase) within 30 minutes of arrival after excluding absolute contraindications (any prior intracranial hemorrhage, ischemic stroke within 3 months, known cerebral vascular malformation or malignancy, suspected aortic dissection, or active internal bleeding). In NSTEMI/Unstable Angina, fibrinolytics are harmful and contraindicated because plasminogen activators lyse the fibrin cap while activating platelets, propagating platelet-rich white thrombi.

Board examinations frequently test the vascular vulnerability of the mitral subvalvular apparatus. The posteromedial papillary muscle receives a single blood supply exclusively from the Posterior Descending Artery (PDA), which arises from the Right Coronary Artery (RCA) in 85% of patients (right-dominant circulation). Consequently, an inferior STEMI predisposes to ischemic necrosis and rupture of the posteromedial papillary muscle 3 to 5 days post-infarction. Conversely, the anterolateral papillary muscle enjoys a dual blood supply from both the Left Anterior Descending (LAD) and Left Circumflex (LCx) arteries, making it highly resistant to ischemic rupture.

Both papillary muscle rupture and interventricular septal rupture present 3 to 5 days after myocardial infarction with acute hemodynamic collapse and a new loud holosystolic murmur. However, papillary muscle rupture follows an inferior MI (RCA), produces a murmur maximal at the cardiac apex radiating to the axilla, causes severe acute pulmonary edema with prominent large V waves on pulmonary capillary wedge pressure (PCWP) tracing, and shows no intracardiac shunt. Septal rupture typically follows an anterior MI (LAD), produces a harsh holosystolic murmur with a palpable parasternal thrill at the left lower sternal border, and demonstrates a diagnostic oxygen saturation step-up (≥ 7–10% increase in SaO₂) between the right atrium and right ventricle on right heart catheterization.

Because the SA node (60%) and AV node (90%) are supplied by branches of the RCA, inferior STEMIs frequently present with sinus bradycardia, first-degree AV block, or Mobitz Type I (Wenckebach) second-degree AV block due to heightened vagal tone (Bezold-Jarisch reflex) and transient AV nodal ischemia. These supra-Hisian blocks carry a benign prognosis and respond briskly to IV atropine. In contrast, anterior STEMIs (LAD occlusion) infarct the intraventricular septum and bundle branch system, causing Mobitz Type II second-degree AV block or complete third-degree infra-Hisian heart block with wide QRS escape rhythms, requiring immediate transvenous pacing.

Vasospastic angina occurs predominantly in younger patients (often female smokers without traditional atherosclerotic risk factors) and is driven by hyperreactivity of coronary vascular smooth muscle, endothelial nitric oxide deficiency, and enhanced Rho-kinase activity. Patients experience recurrent episodes of rest angina occurring clusters between midnight and 8:00 AM associated with transient, reversible ST-segment elevations on 12-lead ECG that normalize upon symptom resolution without troponin elevation. Gold-standard provocative testing uses intracoronary ergonovine or acetylcholine during angiography. First-line maintenance therapy consists of Calcium Channel Blockers (diltiazem, amlodipine, or nifedipine) plus long-acting nitrates and smoking cessation. Non-selective beta-blockers (propranolol) and 5-HT_1B/1D agonists (sumatriptan) are strictly contraindicated.

Cocaine blocks presynaptic reuptake of norepinephrine, epinephrine, and dopamine at sympathetic nerve terminals, producing a massive catecholamine surge. This induces myocardial ischemia via three synergistic mechanisms: (1) increased myocardial oxygen demand from beta-1 mediated tachycardia and inotropy, (2) intense epicardial and microvascular alpha-1 adrenergic coronary vasoconstriction, and (3) accelerated platelet aggregation and thrombus formation. Patients present with chest pain, diaphoresis, mydriasis, agitation, and hypertension. First-line management includes IV benzodiazepines (lorazepam or diazepam) to blunt central sympathetic outflow, aspirin, and sublingual/IV nitroglycerin or calcium channel blockers (diltiazem/verapamil) or phentolamine (alpha-blocker). Beta-blockers must be avoided acutely.

In patients unable to exercise for myocardial perfusion imaging, vasodilator stress agents—regadenoson, adenosine, or dipyridamole (which inhibits adenosine deaminase/reuptake and phosphodiesterase)—stimulate coronary A_2A adenosine receptors, increasing intracellular cAMP and dilating normal resistance arterioles 4- to 5-fold. However, arterioles distal to a critical (> 70%) epicardial coronary stenosis are already maximally dilated at rest via metabolic autoregulation to maintain basal flow. Administering a systemic vasodilator shunts blood away from the stenotic, maximally dilated ischemic territory into healthy low-resistance vessels—a phenomenon termed coronary steal. Caffeine and theophylline are competitive adenosine receptor antagonists and must be held for 24–48 hours prior to testing.

The TIMI (Thrombolysis in Myocardial Infarction) score assigns 1 point for each of 7 variables in NSTE-ACS: (1) Age ≥ 65 years, (2) ≥ 3 traditional CAD risk factors (HTN, DM, dyslipidemia, smoking, family history), (3) Known prior coronary stenosis ≥ 50%, (4) Aspirin use within the past 7 days (indicating breakthrough thrombosis), (5) Severe angina (≥ 2 episodes in 24 hours), (6) ST-segment deviation ≥ 0.5 mm, and (7) Elevated cardiac troponin. Patients with a TIMI score of 0–2 (low risk) undergo non-invasive stress testing; patients with a TIMI score ≥ 3 (intermediate-to-high risk) require an early invasive strategy (coronary angiography within 24 hours). Immediate angiography (< 2 hours) is mandated for refractory angina, hemodynamic instability, ventricular arrhythmias, or acute heart failure.

Once diagnostic coronary angiography defines the obstructive anatomy, revascularization modality (percutaneous stenting vs. surgical CABG) is selected according to survival benefit. CABG provides a definitive mortality reduction over PCI in four board-tested anatomical scenarios: (1) Left main coronary artery stenosis ≥ 50%, (2) Three-vessel coronary disease (LAD, LCx, RCA ≥ 70%), particularly when accompanied by reduced left ventricular ejection fraction (LVEF < 40%), (3) Multivessel (2- or 3-vessel) disease in patients with Diabetes Mellitus involving the proximal LAD, and (4) Two-vessel disease with proximal LAD stenosis ≥ 70% and depressed LVEF or large ischemic territory. The Left Internal Mammary Artery (LIMA) grafted to the LAD achieves > 90% 10-year patency compared to saphenous vein grafts.

High-sensitivity cardiac troponin I or T (hs-cTn) is the gold-standard biomarker for myocardial necrosis, rising within 2 to 3 hours of symptom onset, peaking at 12 to 24 hours, and remaining elevated for 7 to 14 days. Because serial measurements are essential to distinguish acute myocardial injury (dynamic rise and/or fall) from chronic elevation (such as end-stage renal disease or structural heart failure), repeat hs-cTn is drawn at 1 to 3 hours after presentation. While CK-MB was historically used to detect reinfarction (rising at 4–6 hours, normalizing by 48–72 hours), modern guidelines utilize serial troponin trends demonstrating a ≥ 20% recurrent rise if recurrent chest pain develops days after an initial MI.

Standard DAPT (aspirin 81 mg plus a P2Y₁₂ inhibitor) is maintained for 12 months following ACS, regardless of whether a bare-metal stent, drug-eluting stent, or medical management alone was utilized. Premature discontinuation of the P2Y₁₂ inhibitor within the first 30 days to 6 months after drug-eluting stent placement is the single strongest predictor of catastrophic in-stent thrombosis. In patients with a concurrent indication for therapeutic oral anticoagulation (such as atrial fibrillation or venous thromboembolism), prolonged 'triple therapy' (aspirin + clopidogrel + DOAC) causes excessive major gastrointestinal and intracranial bleeding. Current guidelines recommend discontinuing aspirin at hospital discharge (or within 1–4 weeks) and continuing dual therapy with a DOAC (apixaban or rivaroxaban) plus clopidogrel for 12 months.

A crucial board exam pitfall involves the timing of primary-prevention Implantable Cardioverter-Defibrillator (ICD) placement after an acute myocardial infarction. Although ischemic cardiomyopathy with reduced ejection fraction predisposes to lethal ventricular arrhythmias, stunned and hibernating myocardium frequently recovers systolic contractility following successful revascularization and GDMT titration. Therefore, primary prevention ICD implantation is never performed during the acute hospitalization; clinicians must wait at least 40 days post-MI (and ≥ 90 days post-revascularization via PCI or CABG) before reassessing left ventricular ejection fraction. An ICD is indicated at that milestone if LVEF remains ≤ 35% with NYHA Class II–III symptoms (or ≤ 30% with NYHA Class I).

Every ACS patient receives immediate high-intensity statin therapy (atorvastatin 80 mg or rosuvastatin 40 mg) to reduce LDL cholesterol by ≥ 50% and achieve a target LDL-C < 55–70 mg/dL. If follow-up fasting lipid profile at 4 to 12 weeks shows LDL-C remains ≥ 70 mg/dL despite maximally tolerated statin therapy, the next step is adding ezetimibe 10 mg daily (which inhibits the NPC1L1 cholesterol transporter at the intestinal brush border). If LDL-C remains ≥ 70 mg/dL on statin plus ezetimibe, a PCSK9 monoclonal antibody (evolocumab or alirocumab) is added to prevent degradation of hepatic LDL receptors. Additionally, patients with post-MI left ventricular dysfunction or type 2 diabetes should be initiated on an SGLT2 inhibitor (empagliflozin or dapagliflozin) to reduce heart failure hospitalizations.