Non-ST-Segment Elevation Acute Coronary Syndrome (Non-ST-Segment Elevation Myocardial Infarction and Unstable Angina)¶
Chapter 285 | Part 6: Disorders of the Cardiovascular System · Part 6 – Cardiovascular Disorders · Chapter 285
Key Clinical Points¶
- NSTE-ACS includes Non-ST-Segment Elevation Myocardial Infarction (NSTEMI) and Unstable Angina (UA).
- NSTEMI is defined by elevated cardiac troponin (cTn) >99th percentile without ST-segment elevation.
- UA is defined by ischemic symptoms without ST-segment elevation and without myocardial necrosis.
- Pathophysiology involves plaque fissure with inflammation, plaque fissure without inflammation, plaque erosion, or vasospasm.
- Vulnerable plaques are characterized by a lipid-rich core and a thin, collagen-poor fibrous cap.
- TIMI Risk Score (0–7) and GRACE score (>140) are used to stratify risk for immediate vs. delayed invasive strategies.
- Dual Antiplatelet Therapy (DAPT) consists of Aspirin plus a P2Y12 inhibitor (Clopidogrel, Prasugrel, or Ticagrelor).
- Parenteral anticoagulation (UFH, Enoxaparin, Bivalirudin, Fondaparinux) is standard in the acute phase.
- Nitrates are used for symptom relief but are contraindicated with recent PDE-5 inhibitor use (sildenafil <24h, tadalafil <48h).
- Beta-blockers reduce myocardial oxygen demand; contraindicated in acute heart failure or severe bradycardia.
- Calcium Channel Blockers are considered for vasospastic angina or when beta-blockers are contraindicated.
- High-risk NSTE-ACS (TIMI >3, GRACE >140) requires an immediate invasive strategy (<2 hours).
DEFINITION & OVERVIEW¶
• NSTE-ACS Classification: ◦ STEMI: Patients with ST-segment elevation on presenting ECG. ◦ NSTEMI: Patients with chest discomfort (without ST-segment elevation) who develop evidence of myocardial necrosis, reflected by elevated troponin (>99th percentile). ◦ Unstable Angina (UA): Patients with NSTE-ACS who do not have evidence of myocyte necrosis.
Clinical Trends¶
• NSTEMI Prevalence: Increasing due to the burden of obesity, diabetes, and chronic kidney disease in an aging population. • Impact of hsTn: The use of highly sensitive troponin (hsTn) assays has led to a higher rate of NSTEMI diagnosis as cases previously classified as UA are reclassified due to detected myocardial necrosis.
ETIOLOGY & PATHOPHYSIOLOGY¶
• Mechanism: Imbalance between myocardial oxygen supply and demand. • Coronary Thrombosis Drivers: ◦ Plaque fissure with inflammation (T-cell activity). ◦ Plaque fissure without inflammation. ◦ Plaque erosion (present in ≥1/3 of ACS cases). ◦ Non-thrombotic causes: Epicardial or microvascular spasm, or increased demand with fixed obstruction.
Plaque Morphology¶
• Vulnerable Plaque Features: ◦ Morphology: Eccentric stenosis, scalloped/overhanging edges, narrow neck. ◦ Composition: Lipid-rich core, thin fibrous cap (collagen-poor), many macrophages. • Ruptured Plaque: Thin fibrous cap, collagen-poor, large lipid core, many macrophages → Fibrin-rich 'red' thrombus. • Eroded Plaque: Proteoglycan/Glycosaminoglycan rich, little or no lipid core, neutrophils and NETs (Neutrophil Extracellular Traps), many smooth muscle cells → Platelet-rich 'white' thrombus.
CLINICAL FEATURES¶
• Chest Discomfort Criteria (must have at least one): ◦ Occurrence at rest or with minimal exertion, lasting >10 min. ◦ Recent onset (within the prior 2 weeks). ◦ Crescendo pattern (more severe/prolonged/frequent than previous episodes). • Location: Substernal region; radiates to left arm, shoulder, neck, and jaw. • Anginal Equivalents: Dyspnea, epigastric discomfort, nausea, or weakness (common in women, elderly, and patients with DM).
Physical Examination & ECG¶
• Physical Findings: May be unremarkable; severe cases may present with diaphoresis, pale/cool skin, sinus tachycardia, S3/S4 heart sounds, basilar rales, hypotension, or cardiogenic shock. • ECG Findings: ◦ New ST-segment depression (1/3 of patients). ◦ T-wave inversions (≥0.3 mV) are specific signs of ischemia. ◦ STEMI: Rise and fall ST segment elevation + elevated hs-cTn. ◦ NSTEMI: Non-elevated ST segment, ST depression, elevated hs-cTn.
DIFFERENTIAL DIAGNOSIS¶
• Non-Cardiac Causes of Troponin Elevation: ◦ Sepsis ◦ Chronic kidney disease (CKD) ◦ Stroke, subarachnoid hemorrhage ◦ Pulmonary embolism ◦ Infiltrative diseases (amyloidosis, sarcoidosis) ◦ Chemotherapeutic agents ◦ Critical illness ◦ Strenuous exercise • Cardiac Conditions: ◦ Heart failure ◦ Myocarditis ◦ Cardiomyopathy ◦ Takotsubo syndrome ◦ Recent coronary revascularization ◦ Cardiac procedure (other than revascularization) ◦ Catheter ablation ◦ Defibrillator shocks ◦ Cardiac contusion
INVESTIGATIONS & DIAGNOSIS¶
- Cardiac Biomarkers: ◦ Use high-sensitivity (hs) cTn (I or T) as preferred markers. ◦ NSTEMI identified by troponin rise/fall peaking at 12–24h post-symptoms. ◦ Rule-out: 1-h rapid rule-out MI algorithm (no abnormal elevation of hsTn at 0 or 1 h).
- ECG Monitoring: ◦ Continuous monitoring for ST-segment deviation and arrhythmias.
- Risk Scoring Systems: ◦ TIMI (Thrombolysis in Myocardial Infarction) ◦ GRACE (Global Registry of Acute Coronary Event) ◦ HEART (history, electrocardiogram, age, risk factors, troponin).
- Decision Pathways:
Flowchart 1: Spectrum of ACS Decision Matrix - Step 1: Assess ECG for ST-segment elevation. - If Yes → Diagnosis: STEMI. - If No → Proceed to Step 2. - Step 2: Assess hs-cTn levels. - If 'Rise and fall' → Diagnosis: NSTEMI. - If 'Non-elevated' → Diagnosis: Unstable Angina (UA).
Flowchart 2: HEART Pathway for Acute Chest Pain - Step 1: Evaluate ECG. - If STEMI → Follow STEMI guidelines. - If Nonischemic or Ischemic → Proceed to Step 2. - Step 2: Assess 'Known CAD' status. - If No Known CAD → Determine HEART Score. - If Score 0–3 → Evaluate Serial Troponins. - If <99th% → Early discharge. - If ≥99th% → Cardiology consult & admission. - If Score ≥4 → Cardiology consult & admission. - If Yes (Known CAD) → Assess Initial Troponin. - If <99th% → Observation or admission. - If ≥99th% → Stress or coronary angiography.
Risk Stratification (TIMI Score)¶
• TIMI Risk Markers & Incidence of Adverse Events: ◦ Age ≥65: 5% ◦ Known CAD (≥50% stenosis): 8% ◦ ST deviation >0.5 mm: 13% ◦ \uparrow cardiac markers: 20% ◦ ≥2 original episodes in prior 24 h: 26% ◦ Prior angina: 41%
MANAGEMENT & TREATMENT¶
- Anti-Ischemic Drugs: • Nitrates: ◦ Sublingual/buccal (0.3–0.6 mg) for immediate relief. ◦ IV Nitroglycerin (5–10 μg/min); increase by 10 μg/min every 3–5 min until symptoms relieved. ◦ Contraindications: Recent PDE-5 inhibitor use (sildenafil <24h, tadalafil <48h), hypotension, right ventricular infarct, severe aortic stenosis. • Beta-blockers: ◦ Reduce myocardial oxygen demand; contraindicated in acute heart failure or severe bradycardia. • Calcium Channel Blockers: ◦ Consider for vasospastic angina or if beta-blockers are contraindicated. ◦ Contraindications: Systolic pressure <90 mmHg, pulmonary edema, left ventricular dysfunction. Avoid short-acting nifedipine.
- Antithrombotic Therapy: • Aspirin: Loading 150–325 mg (nonenteric); Maintenance 75–100 mg/d. • P2Y Inhibitors: ◦ Ticagrelor: Load 180 mg; Maintain 90 mg BID. ◦ Prasugrel: Pre-PCI load 60 mg; Maintain 10 mg/d (5 mg if weight <60 kg or age >75). ◦ Clopidogrel: Load 600 mg (if PCI planned) or 300 mg (if no PCI planned); Maintain 75 mg/d. ◦ Cangrelor: Bolus 30 μg/kg; Infusion 4 μg/kg/min for 2h or duration of procedure. • Parenteral Anticoagulants: ◦ UFH: Bolus 70–100 U/kg (max 5000); Infuse 12–15 U/kg/h (target ACT 250–300 s). ◦ Enoxaparin: 0.5 mg/kg IV bolus or 1 mg/kg SC every 12 h; adjust to 1 mg/kg daily if CrCl <30 mL/min. ◦ Bivalirudin: Bolus 0.75 mg/kg; Infuse 1.75 mg/kg/h. ◦ Fondaparinux: 2.5 mg SC daily (only prior to PCI).
- Invasive Strategy Selection: • Very High Risk (e.g., Cardiogenic shock, acute severe ischemia, GRACE >140) → Immediate (<2 hours). • High Risk (e.g., ST deviation, positive biomarkers) → Early (<24 hours). • Non-High Risk → Selective invasive approach based on clinical/non-invasive assessment.
Summary of Antithrombotic Agents¶
• Aspirin: 150–325 mg (Load); 75–100 mg/d (Maint). • Clopidogrel: 600/300 mg (Load); 75 mg/d (Maint). • Prasugrel: 60 mg (Pre-PCI); 10/5 mg (Maint). • Ticagrelor: 180 mg (Load); 90 mg BID (Maint). • Cangrelor: 30 μg/kg (Bolus); 4 μg/kg/min (Infusion). • UFH: 70–100 U/kg (Bolus); 12–15 U/kg/h (Infusion). • Enoxaparin: 0.5 mg/kg (IV Bolus) or 1 mg/kg (SC every 12h). • Bivalirudin: 0.75 mg/kg (Bolus); 1.75 mg/kg/h (Infusion). • Fondaparinux: 2.5 mg SC daily.
PROGNOSIS & COMPLICATIONS¶
• Risk Stratification: ◦ TIMI Score ≥3 or GRACE >140 indicates high risk for adverse events (death, MI, recurrent ischemia). • Complications: Potential for heart failure, cardiogenic shock, and malignant arrhythmias in severe cases.
KEY PEARLS & CLINICAL TRAPS¶
• NSTEMI vs. UA: Differentiation is based on the presence of myocardial necrosis (troponin elevation). • Nitrate Safety: Always verify PDE-5 inhibitor use before administering nitrates. • Invasive Timing: ◦ Very High Risk → <2h. ◦ High Risk → <24h. ◦ Non-High Risk → Selective.
Reference Tables¶
TABLE 285-1 TIMI Risk Score for¶
Harrison's 22e, p.2107
| RISK MARKERS | |
|---|---|
| • Age ≥65 years • Known CAD (≥50% stenosis) • ST deviation >0.5 mm on presenting ECG |
• ↑ cardiac markers • ≥2 original episodes in prior 24 h • Prior angina • ≥3 CAD risk factors |
| NO. OF RISK MARKERS | INCIDENCE OF ADVERSE CARDIAC EVENTSa (%) |
| 0/1 | 5 |
| 3 | 13 |
| 5 | 26 |
TABLE 285-2 Reasons for the Elevation of Cardiac Troponin Values as a Result of Myocardial Injury Myocardial injury…¶
Harrison's 22e, p.2109
- Myocardial injury related to acute myocardial infarction
- Atherosclerotic plaque disruption or erosion with thrombosis
- Myocardial injury related to acute myocardial ischemia because of
oxygen supply/demand imbalance - Reduced myocardial perfusion
• Coronary artery spasm, microvascular dysfunction
• Coronary embolism
• Coronary artery dissection
• Sustained bradyarrhythmia
• Hypotension or shock
• Respiratory failure
• Severe anemia - Increased myocardial oxygen demand
• Sustained tachyarrhythmia
• Severe hypertension - Other causes of myocardial injury
- Cardiac conditions
• Heart failure
• Myocarditis
• Cardiomyopathy (any type)
• Takotsubo syndrome
• Recent coronary revascularization
• Cardiac procedure other than revascularization
• Catheter ablation
• Defibrillator shocks
• Cardiac contusion - Systemic conditions
• Sepsis
• Chronic kidney disease
• Stroke, subarachnoid hemorrhage
• Pulmonary embolism
• Infiltrative diseases, e.g., amyloidosis, sarcoidosis
• Chemotherapeutic agents
• Critical illness
• Strenuous exercise
TABLE 285-3 Recommendations for Anti-Ischemic Drugs in the Acute Phase of¶
Harrison's 22e, p.2109
| THERAPY | RECOMMENDATION | WHEN TO AVOID |
|---|---|---|
| Nitrates | • Use sublingual or intravenous nitrates to relieve angina • Use intravenous nitrates if recurrent angina, uncontrolled hypertension, or signs of heart failure • Consider in patients with vasospastic angina |
• Recent use of a PDE-5 inhibitora • Hypotension • Right ventricular infarct • Severe aortic stenosis |
| • Initiate early for ischemic symptoms • Continue chronic therapy |
||
| Calcium channel blockers |
• Consider in patients with vasospastic angina • Consider in patients with contraindications to beta blockers |
• Systolic pressure <90 mmHg • Pulmonary edema • Left ventricular dysfunctionb • Avoid short-acting nifedipine |
| • Continued severe angina despite 3 sublingual nitroglycerin tablets • Recurrent ischemia despite adequate anti- ischemic therapy |
TABLE 285-4 Clinical Use of Antithrombotic Therapy Oral Antiplatelet Therapy Aspirin¶
Harrison's 22e, p.2110
| Oral Antiplatelet Therapy | |
|---|---|
| Aspirin | Loading dose of 150–325 mg orally of nonenteric formulation followed by 75–100 mg/d of an enteric or a nonenteric formulation |
| Clopidogrel | Loading dose of 600 mg (if PCI planned) or 300 mg (if no PCI planned), followed by 75 mg/d |
| Prasugrel | Pre-PCI: Loading dose of 60 mg followed by 10 mg/d In patient with body weight <60 kg or >75 years old, maintenance dose of 5 mg/d |
| Ticagrelor | Loading dose of 180 mg followed by 90 mg twice daily |
| Intravenous Antiplatelet Therapy at the Time of PCI | |
| Parenteral Anticoagulantsa | |
| Unfractionated heparin |
Bolus 70–100 U/kg (maximum 5000 U) IV followed by infusion of 12–15 U/kg per h titrated to ACT 250–300 s |
| Enoxaparin | 0.5 mg/kg IV bolus at the time of PCI or 1 mg/kg subcutaneous every 12 h; the first dose may be preceded by a 30-mg IV bolus; renal adjustment to 1 mg/kg once daily if creatine clearance <30 mL/min |
| Bivalirudin | Initial IV bolus of 0.75 mg/kg followed by an infusion of 1.75 mg/kg per h |
| Fondaparinux | 2.5 mg subcutaneously daily (only prior to PCI) |
| Oral Anticoagulant Drugs (concomitant treatment after PCI) |