Acute Coronary Syndrome: Non–q-Wave (Non–st-Elevation) Mi



  • Non–ST-elevation myocardial infarction (NSTEMI) is a part of the acute coronary syndrome that also includes unstable angina and ST-elevation MI (STEMI)
  • Caused by subtotal occlusion of coronary blood flow:
    • Often indicates an incomplete ischemic event
  • Coronary plaque disruption:
    • Endothelial disruption exposes subendothelial collagen and other platelet-adhering ligands, von Willebrand factor (vWF), and fibronectin
    • Release of tissue factors activates factor VII and the extrinsic pathway
  • Thrombus generation:
    • Platelet adhesion via glycoprotein (GP) Ia/IIa to collagen; GP Ib to vWF:
      • Platelet activation: Release of ADP, thromboxane A2, and serotonin alters the platelet GP IIb/IIIa receptor; also causes local vasoconstriction
      • Platelet aggregation: GP IIb/IIIa receptor binds fibrinogen, cross-links platelets, forming local platelet plug
    • Platelet stabilization: Thrombin converts fibrinogen to fibrin, provides fibrin mesh, stabilizes platelet aggregate
  • Microembolization to downstream coronary arterioles may occur
  • NSTEMI patients are older and have more comorbidities than STEMI patients


  • Coronary thrombosis
  • Coronary vasospasm (idiopathic or cocaine induced)
  • In situ thrombosis/hypercoagulable states
  • Embolic event (e.g., endocarditis, paradoxical emboli through patent foramen ovale [PFO])
  • Arteritis


Signs and Symptoms

  • Pain:
    • Pressure, tightness, or heaviness
    • Substernal, epigastric
    • +/− radiation to arm, jaw, back
    • More likely nonpositional, nonpleuritic, nonreproducible on palpation
  • Nausea, vomiting
  • Diaphoresis
  • Cough
  • Dyspnea
  • Anxiety
  • Lightheadedness
  • Syncope
  • Recent cocaine or amphetamine use
  • Family history of coronary disease
  • Atypical presentations common, especially in women, diabetics, and the elderly

Geriatric Considerations
Geriatric patients may present with atypical symptoms or silent ischemia.

Physical Exam
  • Pallor or diaphoresis
  • Hypertension or hypotension
  • Arrhythmias
  • S4 gallop
  • Physical exam is often normal

Essential Workup

ECG, cardiac biomarkers, CXR

Diagnostic Tests and Interpretation

  • Cardiac markers:
    • Troponins: Specific indicators of myocardial infarction, rise within 2–4 hr after MI, peak at 1–2 d, and return to normal in about 10 d
    • Creatine kinase (CK): Rises within 3–4 hr, peaks at 18–24 hr, subsides at 3–4 d; isoenzyme CK-MB more specific for cardiac origin
    • Myoglobin: Rises within 1–6 hr, returns to baseline within 24 hr, highly sensitive but very nonspecific
    • LDH: Rises within 24 hr, peaks at 3–6 d, returns to baseline at 8–12 d
  • CBC
  • Serum electrolytes including magnesium
  • PT/PTT/INR for patients on warfarin
  • NT-proBNP: Higher levels correlate with increased mortality in NSTEMI patients

  • ECG:
    • ST-segment depression or transient elevation indicates increased risk.
    • T-wave inversion in regional patterns does not increase risk but helps differentiate cardiac pain from noncardiac pain.
    • Deep (>2 mm) precordial T-wave inversion suggests cardiac ischemia.
  • CXR:
    • To assess heart size, pulmonary edema/congestion, or identify other causes of chest pain
  • Echo (often not part of ED evaluation):
    • To identify wall motion abnormalities and assess ventricular function
  • Radionuclide studies (if conservative management; often not part of ED evaluation):
    • Sestamibi scan: Identify viable myocardium
    • Technetium 99: Identify recently infarcted myocardium

Diagnostic Procedures/Other
Coronary angiography (+/− PCI), typically as an inpatient, depending on patient's risk profile and comorbidities

Differential Diagnosis

  • Pulmonary embolus
  • Aortic dissection
  • Acute pericarditis/myocarditis
  • Pneumothorax
  • Pancreatitis
  • Pneumonia
  • Esophageal spasm/gastroesophageal reflux
  • Esophageal rupture
  • Musculoskeletal pain/costochondritis


Pre Hospital

  • IV access
  • Oxygen administration (if SpO2 <95%)
  • 12-lead ECG, cardiac monitoring, and treatment of arrhythmias
  • Aspirin, analgesia, anxiolytics

Initial Stabilization/Therapy

  • Oxygen administration (if SpO2 <95%)
  • IV access
  • 12-lead ECG, cardiac monitoring, and treatment of arrhythmias

Ed Treatment/Procedures

  • Anti-ischemic therapy to reduce demand and increase supply of oxygen to myocardium:
    • β-Blockers: Consider providing an IV dose only if hypertensive with ongoing pain; contraindicated in heart failure
    • Nitrates: Contraindicated with critical AS, suspicion of RV infarct, or recent use of phosphodiesterase inhibitors (e.g., sildenafil)
    • Oxygen, if hypoxic
    • Morphine sulfate
    • Calcium channel blockers (nondihydropyridines— e.g., diltiazem, verapamil) may be used in patients with ongoing ischemia and contraindications to β-blockade. Contraindicated in heart failure
  • Dual antiplatelet therapy to decrease platelet aggregation:
    • Aspirin: Only withhold if prior anaphylaxis (substitute with clopidogrel)
    • ADP inhibitor: Clopidogrel, ticagrelor, or prasugrel (if low bleeding risk, CABG unlikely, no history of CVA, age <75 yr); these may be delayed until after angiography
  • GP IIb/IIIa inhibitors (eptifibatide, tirofiban):
    • Only if ongoing ischemia, positive cardiac markers and PCI planned; can defer to inpatient administration
    • May omit if loading dose of clopidogrel administered at least 6 hr prior to PCI or bivalirudin used for anticoagulation
  • Anticoagulation therapy to prevent thrombus propagation in patients planned for invasive treatment:
    • Unfractionated heparin and enoxaparin are first-line therapies
    • Fondaparinux (factor Xa inhibitor) is a reasonable alternative, may have reduced bleeding risk
    • Reserve bivalirudin (direct thrombin inhibitor) for patients with known heparin-induced thrombocytopenia
  • Anxiolytics if needed (may suppress sympathetic drive)


First Line Medication:
  • Aspirin 162–325 mg PO per day
  • β-Blockers:
    • Atenolol: Start 5 mg IV over 5 min, then 5 mg IV 10 min later, then 50–100 mg PO per day (1–2 hr after IV doses)
    • Esmolol: 100 mcg/kg/min IV infusion (titrate by increasing 50 mcg/kg/min q15min until effect—to max. dose 300 mcg/kg/min)
    • Metoprolol: Start 5 mg IV q5min × 3, after 15 min begin 25–50 mg PO BID
    • Propranolol: 0.5–1 mg IV then 40–80 mg PO q6–8h
  • Clopidogrel: 300–600 mg PO × 1, then 75 mg/d
  • Heparins:
    • Enoxaparin: 1 mg/kg SC q12h, can give 30-mg IV bolus before SC dose (caution in patients with renal dysfunction) or
    • Unfractionated heparin: 60-U/kg IV bolus then 12-U/kg/hr infusion (max. bolus 4,000 units, max. infusion rate 1,000 U/hr) (goal is a PTT 50–75 s)
  • Morphine sulfate: 1–5 mg IV q5–30min PRN pain
  • Nitroglycerin: 0.3–0.6 mg SL or 0.4 mg by spray q5min followed by IV infusion beginning at 10–20 mcg/min if pain persists (max. dose 200 mcg/min)
  • GP IIb/IIIa inhibitors:
    • Eptifibatide: 180-mcg/kg IV bolus then 2-mcg/kg/min infusion for 72–96 hr
    • Tirofiban: 0.4 mcg/kg/min IV × 30 min, then 0.1 mcg/kg/min infusion for 12–24 hr

Second Line Medication:
  • Calcium channel blockers:
    • Diltiazem: Start 0.25-mg/kg IV bolus, then 0.35 mg/kg IV after 15 min if needed then 30 mg PO q6h: immediate release
    • Verapamil: Start 5–10 mg IV, repeat after 30 min if needed, then 80–160 mg PO q8h: immediate release
  • ADP blocker:
    • Ticagrelor: 180 mg PO × 1 at time of PCI or no later than 1 hr post-PCI, then 90 mg PO BID
    • Prasugrel: 60 mg PO × 1 at time of PCI or no later than 1 hr post-PCI, then 10 mg/d
  • Lorazepam: 1–2 mg IV PRN anxiety
  • Anticoagulation (instead of unfractionated heparin or enoxaparin):
    • Fondaparinux: 2.5 mg SC once a day or
    • Bivalirudin (only prior to PCI): 0.75-mg/kg IV bolus, then 1.75 mg/kg/hr IV for up to 4 hr, then 0.2 mg/kg/hr IV for up to 20 hr

Ongoing Care


Admission Criteria
  • All patients with positive cardiac biomarkers, high risk for adverse outcomes by clinical prediction rules (TIMI, GRACE, PURSUIT, HEART), or significant clinical probability of acute coronary syndrome undergoing consideration for urgent or early invasive management 12–24 hr after presentation
  • Intensive care unit for monitoring unstable patients.

Discharge Criteria
Only those who are ruled out for acute coronary syndrome/non–Q-wave infarction can be safely sent home.

Follow-Up Recommendations

  • Only patients ruled out for acute coronary syndrome can be safely discharged:
    • Discharged patients should follow up in 1–2 d with their primary care physician or cardiologist
    • Outpatient stress tests should be done within 72 hr

Pearls and Pitfalls

  • ECG should be done in all patients with chest pain on arrival to the ED, preferably within 10 min
  • Early medical therapy can reduce mortality in NSTEMI
  • Pitfalls:
    • Do not rule out infarction based on initial or single set of cardiac markers, particularly if the time from symptom onset is <4–6 hr
    • Do not fail to ask about amphetamine or cocaine use
    • Do not fail to ask about use of sildenafil, vardenafil, or tadalafil before giving nitroglycerin

Additional Reading

  • Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 ACC/AHA Guideline for the management of patients with non-ST-elevation acute coronary syndromes. Circulation. 2014;130:e344–e426.
  • Backus BE, Six AJ, Kelder JC, et al. A prospective validation of the HEART score for chest pain patients at the emergency department. Int J Cardiol. 2013;168:2153–2158.
  • Bonaca MP, Steg PG, Feldman LJ, et al. Antithrombotics in acute coronary syndromes. J Am Coll Cardiol. 2009;54:969–984.
  • Braunwald E. Unstable angina and non–ST elevation myocardial infarction. Concise clinical review. Am J Resp Crit Care Med. 2012;185:924–932.
  • Corcoran D, Grant P, Berry C. Risk stratification in non-ST elevation acute coronary syndromes: Risk scores, biomarkers and clinical judgment. IJC Heart & Vasculature. 2015;8:131–137.

See Also

The authors gratefully acknowledge Kenneth R.L. Bernard for his contribution to the previous edition of this chapter.


Nathaniel Mann
David F. M. Brown

© Wolters Kluwer Health Lippincott Williams & Wilkins