2.1 Acute Coronary Syndromes & Myocardial Infarction Management

Pathophysiology of Acute Coronary Syndromes

Acute coronary syndrome (ACS) represents a critical spectrum of ischemic heart disease resulting from an abrupt, acute reduction in coronary arterial blood flow. The unifying underlying trigger in more than 90% of cases is atherosclerotic plaque disruption—either through superficial plaque erosion or deep fibrous cap rupture. Rupture exposes thrombogenic subendothelial core components, predominantly tissue factor, collagen, and von Willebrand factor, directly to the circulating bloodstream.

Upon exposure, circulating platelets undergo rapid adherence via glycoprotein Ib-IX-V receptors, become activated, and release potent agonists including thromboxane A2 and adenosine diphosphate (ADP). This triggers conformational activation of platelet glycoprotein IIb/IIIa receptors, cross-linking circulating fibrinogen into an expanding platelet-rich thrombus. The concurrent activation of the extrinsic coagulation cascade generates a fibrin mesh that stabilizes the clot.

The clinical syndrome is dictated by the degree and duration of luminal obstruction:

• ST-Segment Elevation Myocardial Infarction (STEMI): Results from complete, persistent, transmural occlusive thrombosis of an epicardial coronary artery, producing full-thickness myocardial ischemia and progressive necrosis extending from the vulnerable subendocardium to the epicardium within hours.
• Non-ST-Segment Elevation Myocardial Infarction (NSTEMI): Arises from incomplete, subtotal, or intermittent microembolizing luminal occlusion leading to subendocardial ischemia sufficient to cause biochemical myocyte necrosis (manifested by troponin release) without persistent transmural injury currents.
• Unstable Angina (UA): Involves severe, transient myocardial ischemia in the absence of biochemical evidence of myocyte necrosis (normal troponin levels), presenting with new-onset, rest, or crescendo anginal patterns.

+-----------------------------------------------------------------------------------------+
|                                 Atherosclerotic Plaque                                  |
|                            (Fibrous cap rupture or erosion)                             |
+-----------------------------------------------------------------------------------------+
                                             |
                                             v
+-----------------------------------------------------------------------------------------+
|                         Platelet Activation & Fibrin Deposition                         |
+-----------------------------------------------------------------------------------------+
                                             |
                   +-------------------------+-------------------------+
                   |                                                   |
                   v                                                   v
       [ Complete Occlusion ]                               [ Subtotal Occlusion ]
                   |                                                   |
                   v                                                   v
           Transmural STEMI                                    Non-ST Elevation ACS
       (Persistent ST-Elevation,                                       |
         Troponin Elevated)                        +-------------------+-------------------+
                                                   |                                       |
                                                   v                                       v
                                                NSTEMI                              Unstable Angina
                                         (Troponin Elevated,                     (Normal Biomarkers,
                                         ST/T-Wave Changes)                       Transient Ischemia)

Clinical Presentation & Risk Stratification

The hallmark symptom of ACS is retrosternal chest pain or pressure, classically described as squeezing, heavy, crushing, or band-like, lasting longer than 20 minutes and not relieved by rest or sublingual nitroglycerin. Radiation commonly extends to the left shoulder, ulnar aspect of the left arm, both arms, the neck, or the mandible. Associated autonomic symptoms include diaphoresis, nausea, vomiting, dizziness, lightheadedness, and profound sense of impending doom.

Atypical presentations are frequent and demand heightened clinical vigilance, especially in elderly patients, females, and individuals with long-standing diabetes mellitus suffering from autonomic neuropathy. These patients often present without chest pain, manifesting anginal equivalents such as acute isolated dyspnea, unexplained fatigue, syncope, epigastric distress resembling peptic ulcer disease, or acute delirium.

Bedside risk stratification guides the urgency of invasive versus non-invasive evaluation. The TIMI (Thrombolysis in Myocardial Infarction) risk score for UA/NSTEMI incorporates 7 clinical variables (age >= 65, >= 3 CAD risk factors, known CAD with stenosis >= 50%, aspirin use in past 7 days, severe angina >= 2 episodes in 24 hours, ST deviation >= 0.5 mm, and positive cardiac biomarkers). The GRACE (Global Registry of Acute Coronary Events) risk score calculates in-hospital and 6-month mortality based on age, heart rate, systolic blood pressure, serum creatinine, Killip class, cardiac arrest at admission, ST-segment deviation, and elevated cardiac enzymes, determining whether urgent (< 2 hours) or early (< 24 hours) coronary angiography is indicated.

Diagnostic ECG Criteria & Anatomical Localization

A 12-lead electrocardiogram (ECG) must be acquired and interpreted within 10 minutes of first medical contact for any patient presenting with suspected ACS. Serial tracings every 15 to 30 minutes are mandatory if the initial tracing is non-diagnostic but symptoms persist.

Formal STEMI Criteria

STEMI is defined by new ST-segment elevation at the J-point in at least two contiguous leads:

1. Precordial Leads V2-V3:
   • Men >= 40 years: >= 2.0 mm (0.2 mV)
   • Men < 40 years: >= 2.5 mm (0.25 mV)
   • Women (all ages): >= 1.5 mm (0.15 mV)
2. All Other Leads (Limb leads I, II, III, aVF, aVL and precordial leads V1, V4-V6):

   • = 1.0 mm (0.1 mV) in men and women

Contiguous lead groupings identify the anatomical territory and the culprit coronary artery:

• Inferior Wall (Leads II, III, aVF): Right Coronary Artery (RCA) in 85-90% (dominant right circulation) or Left Circumflex Artery (LCx). Reciprocal ST depressions are characteristically observed in leads I and aVL.
• Anterior & Septal Wall (Leads V1-V2 septal; V3-V4 anterior): Left Anterior Descending (LAD) artery. Carries high risk of cardiogenic shock, conduction block, and ventricular arrhythmias.
• Lateral Wall (Leads I, aVL, V5, V6): Left Circumflex (LCx) or diagonal branch of LAD. Often associated with reciprocal depression in leads III and aVF.
• Posterior Wall: Occlusion of the distal RCA or circumflex artery produces indirect signs in anterior leads V1-V3 (horizontal ST-segment depression, tall upright symmetric T waves, and prominent R waves with R/S ratio > 1). Posterior lead placement (V7, V8, V9 placed along the posterior axillary line, mid-scapular line, and left paraspinal border at the 5th intercostal space) confirms the diagnosis if ST elevation is >= 0.5 mm.
• Right Ventricular (RV) Infarction: Present in approximately 30-50% of inferior STEMIs due to proximal RCA occlusion. Diagnosed by acquiring right-sided precordial leads (V3R and V4R), where ST elevation >= 1.0 mm in V4R is highly sensitive and specific. Clinically characterized by the classic triad of hypotension, elevated jugular venous pressure with clear lung fields, and marked sensitivity to preload reduction.

Left Bundle Branch Block & Sgarbossa Criteria

A new or presumably new Left Bundle Branch Block (LBBB) obscures normal ST-segment dynamics due to secondary repolarization abnormalities. The modified Sgarbossa criteria identify acute transmural infarction in the setting of LBBB or ventricular pacing:

• Concordant ST elevation >= 1 mm in any lead with a positive QRS complex (Score: 5 points).
• Concordant ST depression >= 1 mm in lead V1, V2, or V3 (Score: 3 points).
• Excessively discordant ST elevation defined by the modified rule as ST elevation >= 1 mm that is disproportionate to the preceding S wave, specifically an ST/S ratio <= -0.25 (i.e., ST elevation >= 25% of the depth of the S wave). A score >= 3 or a positive modified third criterion warrants immediate activation of the reperfusion pathway.

Immediate Anti-Ischemic & Antithrombotic Management

Immediate medical stabilization must proceed in parallel with diagnostic triage. The traditional "MONA" mnemonic requires strict contemporary refinement:

1. Antiplatelet Therapy (DAPT):
   • Aspirin: Administer an immediate non-enteric coated loading dose of 162 to 325 mg (or 300 mg chewable) crushed or chewed, followed by an indefinite maintenance dose of 75 to 100 mg daily. Aspirin inhibits platelet cyclooxygenase-1 (COX-1), blocking thromboxane A2 production.
   • P2Y12 Receptor Antagonist: Co-administered with aspirin. For primary PCI, potent agents are preferred: Ticagrelor (180 mg loading dose, then 90 mg twice daily) or Prasugrel (60 mg loading dose; maintenance 10 mg daily, or 5 mg with caution if weight<60 kg or age≥75; contraindicated after prior TIA/stroke). Clopidogrel is used with fibrinolysis: load 300 mg if age≤75, or give 75 mg without loading if age>75, then 75 mg daily. Without fibrinolysis, the loading dose is 300–600 mg when clopidogrel is selected.
2. Anticoagulation:
   • Enoxaparin (LMWH): Initial NSTE-ACS treatment is 1 mg/kg subcutaneously every 12 hours. With fibrinolysis, age<75:30 mg IV then 1 mg/kg subcutaneously every 12 hours (first two doses≤100 mg each); age≥75:omit the IV bolus and use 0.75 mg/kg every 12 hours (first two doses≤75 mg each). If creatinine clearance<30 mL/min, use 1 mg/kg subcutaneously every 24 hours.
   • Unfractionated Heparin (UFH): For PCI without previous anticoagulation, give 70–100 units/kg IV and adjust to an activated clotting time (ACT) of 250–300 seconds. If anticoagulation was already given, use additional UFH according to ACT. Medical-treatment and fibrinolysis infusion regimens are separate protocols.
   • Fondaparinux: Factor Xa inhibitor; preferred in NSTEMI managed conservatively due to lowest bleeding risk, but requires supplementary UFH during PCI to prevent catheter thrombosis.
3. Nitrates:
   • Sublingual nitroglycerin (0.4 mg every 5 minutes up to 3 doses) reduces myocardial oxygen demand via peripheral venodilation (preload reduction) and dilates coronary epicardial vessels. IV nitroglycerin is titrated for refractory ischemia, uncontrolled hypertension, or acute heart failure.
   • Absolute Contraindications: Systolic blood pressure < 90 mmHg, severe bradycardia (< 50 bpm), tachycardia (> 100 bpm in the absence of heart failure), suspected right ventricular infarction, or phosphodiesterase-5 (PDE-5) inhibitor usage within the prior 24 hours (sildenafil, vardenafil) or 48 hours (tadalafil), which risks fatal refractory hypotension.
4. Analgesia & Oxygen:
   • Supplemental Oxygen: Indicated only if arterial oxygen saturation (SpO2) is < 90% or PaO2 < 60 mmHg. Routine hyperoxia induces paradoxical coronary vasoconstriction and augments reactive oxygen species production.
   • Opioids: Intravenous morphine (2 to 4 mg IV repeated every 5 to 15 minutes) is reserved strictly for severe refractory pain. Routine administration is discouraged because morphine delays the gastrointestinal absorption and onset of oral P2Y12 inhibitors.
5. Oral Beta-Blockers & Statins:
   • Early oral beta-blocker therapy (e.g., metoprolol tartrate 25-50 mg or bisoprolol 2.5-5 mg) within the first 24 hours reduces myocardial work and ventricular arrhythmias. However, it must be withheld in patients demonstrating signs of acute heart failure, low output state, increased risk of cardiogenic shock (age > 70, heart rate > 110, SBP < 120 mmHg), or AV conduction blocks.
   • High-intensity statin therapy (Atorvastatin 80 mg or Rosuvastatin 40 mg daily) should be initiated as early as possible before discharge regardless of baseline cholesterol levels.

Reperfusion Strategies: Primary PCI vs. Fibrinolytic Therapy

Timely reperfusion is the paramount prognostic determinant in STEMI. Myocardial salvage diminishes precipitously as ischemic time increases.

Primary Percutaneous Coronary Intervention (PCI)

Primary PCI is preferred for STEMI. The 2025 ACC/AHA targets are first medical contact (FMC) to device activation within 90 minutes at a PCI-capable centre or 120 minutes when hospital transfer is needed. FMC and the time of STEMI diagnosis are distinct timestamps. Primary PCI achieves superior rates of vessel patency (TIMI 3 flow in > 90% vs ~60% with thrombolysis), lower re-infarction rates, and has a lower intracranial hemorrhage risk than fibrinolysis.

Intravenous Fibrinolytic Therapy

For STEMI with symptom onset <12 hours, give fibrinolysis promptly if anticipated FMC-to-device time exceeds 120 minutes and there is no contraindication. The door-to-needle target is <30 minutes. Late presentation, uncertain timing or contraindications require urgent PCI-centre assessment; transfer delay alone is not an automatic indication for lysis.

Fibrin-specific agents are preferred:

• Tenecteplase (TNK-tPA): Administered as a single weight-based intravenous bolus over 5 to 10 seconds (30 mg for < 60 kg up to 50 mg for >= 90 kg; dose reduced by 50% in patients aged >= 75 years).
• Alteplase (rt-PA): Administered as an accelerated 90-minute weight-adjusted infusion (15 mg IV bolus, then 0.75 mg/kg over 30 min (maximum 50 mg), then 0.5 mg/kg over 60 min (maximum 35 mg); total dose≤100 mg).

Arrange immediate transfer to a PCI-capable centre after fibrinolysis, without waiting to assess success. Assess reperfusion at 60 to 90 minutes during transfer or at the receiving centre. Successful reperfusion is signified by >= 50% resolution of the initial ST-segment elevation, abrupt relief of chest discomfort, and transient reperfusion arrhythmias (e.g., accelerated idioventricular rhythm). If fibrinolysis fails (< 50% ST resolution at 90 minutes) or hemodynamic instability emerges, perform urgent angiography with rescue PCI. After successful fibrinolysis, perform angiography with intent to undertake PCI within 2 to 24 hours; this is the angiography window, not permission to delay transfer.

Mechanical & Electrical Complications Post-MI

Despite advances in reperfusion, ischemic myocardial necrosis carries substantial risk of acute mechanical collapse, predominantly occurring between day 3 and day 7 post-infarction as necrotic tissue undergoes enzymatic lysis and macrophage infiltration prior to collagen deposition.

1. Acute Ventricular Septal Defect (VSD):
   • Occurs following extensive anterior MI (apical septal perforation via LAD) or inferior MI (basal septal perforation via RCA).
   • Clinical signs: Abrupt hemodynamic collapse, acute biventricular failure, and a new, harsh, loud holosystolic murmur heard best along the left lower sternal border, accompanied by a palpable systolic thrill in > 50% of cases.
   • Diagnosis: Bedside transthoracic echocardiography (TTE) with color Doppler reveals left-to-right shunting. Pulmonary artery catheterization confirms an oxygen saturation step-up >= 10% from the right atrium to the right ventricle.
   • Management: Emergency hemodynamic stabilization, selected mechanical circulatory support (such as IABP), and urgent surgical or percutaneous repair. IV nitroprusside may reduce afterload if blood pressure permits.
2. Papillary Muscle Rupture:
   • Affects the posteromedial papillary muscle ten times more frequently than the anterolateral muscle because the posteromedial muscle has a single blood supply (posterior descending artery from RCA or LCx), whereas the anterolateral papillary muscle receives dual blood supply (LAD and LCx).
   • Clinical signs: Catastrophic flash pulmonary edema, cardiogenic shock, and a new, soft, blowing apical pansystolic murmur radiating to the axilla. Notably, the murmur may be soft or deceptively absent due to the rapid equalization of left ventricular and left atrial pressures in an acute, non-compliant atrium.
   • Diagnosis: Emergency TTE demonstrates acute severe mitral regurgitation with a flail mitral leaflet.
   • Management: Immediate hemodynamic stabilization and selected circulatory support, followed by emergency surgical valve repair or replacement; use vasodilator afterload reduction only when blood pressure permits.
3. Left Ventricular Free Wall Rupture:
   • Occurs most often in elderly females with first transmural anterior or lateral MIs and poor collateral circulation.
   • Clinical signs: Sudden, catastrophic hemopericardium, cardiac tamponade, and pulseless electrical activity (PEA) arrest. Subacute 'pseudoaneurysm' formation may produce transient chest pain and pericardial friction rub before frank blowout.
   • Emergency care: Often rapidly fatal; obtain urgent bedside echocardiography and surgical repair. Controlled pericardial drainage may temporarily stabilize tamponade when surgery is not immediately available, but must not delay definitive surgery.
4. Post-MI Electrical Complications:
   • Ventricular Fibrillation (VF): Primary VF occurs within the initial 48 hours due to acute electrical instability in ischemic tissue; treated with immediate unsynchronized defibrillation. Secondary or late VF (> 48 hours) reflects severe LV dysfunction and scar tissue, carrying a poor long-term prognosis requiring an implantable cardioverter-defibrillator (ICD).
   • Atrioventricular Block: Common in inferior STEMI due to RCA ischemia of the AV node (nodal level block; usually transient, responsive to atropine). In anterior STEMI, AV block is infranodal (His-Purkinje system necrosis), manifesting as Mobitz II or complete heart block with wide QRS escape rhythm, unresponsive to atropine, and carrying high mortality requiring immediate pacing.