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Acute Coronary Syndromes: Unstable Angina and NSTEMI

para>ST-segment depression and/or T-wave inversion:
  • ≥1-mm ST depression in ≥2 contiguous leads

  • T-wave inversions, other changes

  • ST depression and/or tall R wave in V1/V2 with upright T waves may indicate transmural STEMI of posterior wall.

  • If initial ECG is nondiagnostic but symptoms persist with suspicion for ACS, perform serial ECGs at 15-30-minute intervals.

  • Serum biomarkers (negative by definition in UA)
    • NSTEMI is strictly defined as a rise and fall in serum biomarkers (usually troponin I or T, as they are more sensitive for detecting NSTEMI) exceeding the 99th percentile of a normal reference population. Troponin concentration rises 3-6 hours after onset of ischemic symptoms but can be delayed to 8-12 hours (troponin T is not specific in patients with renal dysfunction).

    • CK-MB increases 3-4 hours after onset of myocardial injury.

    • Myoglobin: early marker for myocardial necrosis; increases 2 hours after onset of myocardial necrosis

    • Patients with negative biomarkers within 6 hours of the onset of symptoms should have biomarkers remeasured 8-12 hours from onset of symptoms

  • Chest x-ray
  • Consider transthoracic echocardiography if not recently performed (1)[B].

  • Follow-Up Tests & Special Considerations
    • Patients with ischemia are recommended to undergo an assessment of left ventricle (LV) function to identify impaired function and/or need for appropriate medications such as ACE inhibitors, beta-blockers, and aldosterone antagonists.
    • Fasting lipid profile
    • Complete blood count(CBC), basic metabolic panel, activated partial thromboplastin time (aPTT)
    • Other laboratory tests:
      • Lactate dehydrogenase: increases within 24 hours, peaks 3-6 days, baseline 8-12 days (not routinely ordered)

      • Leukocytes: increase within several hours after MI, peak in 2-4 days

      • Brain natriuretic peptide (BNP): increases with MI, may not indicate heart failure


    Pregnancy Considerations
    Findings mimicking NSTEMI in pregnancy: ST depression after anesthesia, increase in CK-MB after delivery, and mild increase in troponin in preeclampsia and gestational hypertension. Spontaneous coronary dissection is a rare cause of ST elevation in pregnancy.  
    Diagnostic Procedures/Other
    • Coronary angiography (discussed under "Treatment"ť)
    • If serial cardiac enzymes are negative and symptoms have resolved, consider stress testing, including either standard exercise treadmill test (ETT), stress echocardiography, or stress nuclear study (1)[B].
    • Transesophageal echocardiography, contrast chest CT scan, or MRI generally are reserved for differentiating acute coronary syndrome and other causes of chest pain from aortic dissection.

    Test Interpretation
    • Subendocardial myocardial necrosis may be present.
    • Atherosclerosis

    Treatment


    General Measures


    • Bed/chair rest with continuous ECG monitoring
    • Antiarrhythmics as needed
    • Anxiolytics as needed
    • Deep vein thrombosis prophylaxis
    • Continuation of aspirin, clopidogrel or prasugrel or ticagrelor, beta-blockers, ACE inhibitors (or ARBs if ACE intolerant), lipid-lowering therapy
    • Tight BP control
    • Treatment for depression PRN (common post-MI)
    • Cardiac rehabilitation and increased physical activity
    • Smoking cessation
    • Annual influenza vaccine

    Medication


    First Line
    • Aspirin, nonenteric-coated, initial dose of 162-325 mg PO or chewed to all patients (1)[A]
      • In patients planned for PCI who are not at high risk for complex disease requiring coronary artery bypass graft (CABG) surgery, administer clopidogrel, loading dose 300-600 mg followed by 75 mg/day (1)[A]; or prasugrel, loading dose 60 mg followed by 10 mg/day (1)[B]; or ticagrelor, loading dose 180 mg followed by 90 mg BID (1)[B]. (Ticagrelor increases the risk of fatal intracranial hemorrhage [ICH] compared with clopidogrel and should be avoided in those with a prior history of ICH [1]).

      • Patients unable to take aspirin should receive a loading and maintenance dose of either clopidogrel, ticagrelor, or prasugrel.

    • Nitroglycerin (NTG) sublingual 0.4 mg every 5 minutes for total of 3 doses, then assess need for intravenous IV NTG (1)[C]
    • Supplemental oxygen 2-4 L/min, maintaining arterial oxygen saturation >90% (1)[B]
    • Morphine sulfate 2-4 mg IV (with increments of 2-8 mg IV repeated at 5-15-minute intervals (1)[A]
    • Oral beta-blocker (cardioselective agent such as metoprolol or atenolol preferred) in patients without signs of heart failure, cardiogenic shock, or other contraindications (1)[B]
    • Risk stratify using the TIMI or GRACE score to select use of early invasive approach (within 12-24 hours of admission) versus medical therapy.
    • Risks and benefits of the early invasive approach:
      • 33% relative risk reduction for both the end points of refractory angina and rehospitalization at 6-12 months (2)[A]

      • 27% and 22% relative risk reduction in rates of MI at 6-12 months and 3-5 years, respectively (2)[A]

      • Doubled risk of procedure-related MI and increased risk of minor periprocedural bleeding (1)[A]

    • Invasive management
      • Benefits are more pronounced in higher risk patients, such as those with ECG changes or diabetes (2).

    • Subsequent recommendations (1)[A]: For patients with elevated risk for clinical events or refractory angina or hemodynamic or electrical instability, initiate anticoagulant: enoxaparin or unfractionated heparin (UFH) or bivalirudin. Prior to angiography, add GP IIb/IIIa inhibitor (eptifibatide or tirofiban) or thienopyridine (clopidogrel or ticagrelor).
    • Medical management
      • For low-risk or selected intermediate-risk patients; based on patient or physician preference; or in chronic renal insufficiency stage IV: Initiate anticoagulant therapy: enoxaparin or UFH or fondaparinux; enoxaparin or fondaparinux preferable. Initiate clopidogrel, prasugrel, or ticagrelor (1)[B].

    • Contraindications: Prasugrel and ticagrelor are contraindicated in patients >75 years or those with history of CVA/TIA or increased bleeding risk.

    Second Line
    • ACE inhibitor in patients with pulmonary congestion or left ventricular ejection fraction (EF) ≤40%. Substitute ARB for ACE-intolerant patients (1)[A].
    • Nondihydropyridine calcium channel blocker (CCB) (verapamil or diltiazem) to reduce myocardial oxygen demand when beta-blockers are contraindicated if normal EF (1)[B]. Use oral long-acting CCB only after beta-blockers and nitrates have been fully used (1)[C].
    • Long-term nitrate therapy for recurrent angina/ischemia or heart failure (1)[C].
    • Sublingual NTG at discharge (1)[C]
    • Lipid-lowering therapy: high-dose statin (preferred due to nonlipid benefit on vascular function) (1)[A], niacin, or fibrate (1)[C]

    Issues for Referral


    Cardiology consultation is appropriate for likely UA/NSTEMI, particularly regarding the complexities of anticoagulation/antiplatelet therapy.  

    Surgery/Other Procedures


    • Coronary reperfusion
      • PCI with stent placement

      • CABG surgery

    • Intra-aortic balloon pump for severe ischemia, hypotension, refractory pain

    Inpatient Considerations


    Admission Criteria/Initial Stabilization
    • All patients with definite or suspected acute MI, ongoing pain, positive cardiac markers, ST deviations, hemodynamic abnormalities, probable or definite ACS
    • Bed rest with continuous ECG monitoring, assess for reperfusion therapy, relieve ischemic pain, treat life-threatening complications, admit to coronary care unit.

    Ongoing Care


    Follow-up Recommendations


    • Follow-up within 2-6 weeks (low risk) and 14 days (high risk).
    • Refer to cardiac rehabilitation.

    Diet


    • Diet low in saturated fat, cholesterol, and sodium
    • Request dietary consult

    Patient Education


    • Education on new medications, diet, exercise, smoking cessation, lifestyle modification
    • Resume exercise, sexual activity after outpatient reevaluation

    Prognosis


    UA/NSTEMI patients have lower in-hospital mortality than those with STEMI but a similar or worse long-term outcome.  

    Complications


    • Cardiogenic shock
    • Heart failure
    • Myocardial rupture
    • Ventricular aneurysm
    • Dysrhythmia
    • Acute pulmonary embolism
    • Acute thromboembolic stroke
    • Pericarditis/Dressler syndrome
    • Depression (increases mortality risk)
    • Hyperglycemia

    References


    1.Anderson  JL, Adams  CD, Antman  EM, et al. 2012 ACCF/AHA focused update incorporated into the ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol.  2013;61(23):e179-e347.  [View Abstract]2.Roger  VL, Go  AS, Lloyd-Jones  DM, et al. Heart disease and stroke statistics-2012 update: a report from the American Heart Association. Circulation.  2012;125(1):e2-e220.  [View Abstract]

    Additional Reading


    • Hoenig  MR, Aroney  CN, Scott  IA. Early invasive versus conservative strategies for unstable angina and non-ST elevation myocardial infarction in the stent era. Cochrane Database Syst Rev.  2010;(3): CD004815.  [View Abstract]
    • 2012 Writing Committee Members, Jneid  H, Anderson  JL, et al. 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation.  2012;126(7):875-910.  [View Abstract]

    Codes


    ICD10


    • I24.9 Acute ischemic heart disease, unspecified
    • I20.0 Unstable angina
    • I21.4 Non-ST elevation (NSTEMI) myocardial infarction
    • I20.1 Angina pectoris with documented spasm

    ICD09


    • 411.1 Intermediate coronary syndrome
    • 410.70 Subendocardial infarction, episode of care unspecified
    • 413.1 Prinzmetal angina

    SNOMED


    • 394659003 Acute coronary syndrome (disorder)
    • 4557003 Preinfarction syndrome (disorder)
    • 401314000 Acute non-ST segment elevation myocardial infarction (disorder)
    • 71772004 Vasospasm (finding)

    Clinical Pearls


    • Discontinue NSAIDs, nonselective or selective cyclooxygenase (COX)-2 agents, except for ASA, due to increased risks of mortality, reinfarction, hypertension, heart failure, and myocardial rupture.
    • Discontinue clopidogrel or prasugrel or ticagrelor 5-7 days before elective CABG.
    • Do not use nitrate products in patients who recently used a phosphodiesterase-5 inhibitor (24 hours of sildenafil or 48 hours of tadalafil).
    • Duration of antithrombotic therapy after NSTEMI depends on type of stent received and medications administered.
    • Avoid beta-blockers in cocaine user.
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