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Acute Coronary Syndromes: NSTE-ACS (Unstable Angina and NSTEMI)

para>Elderly patients, as well as women and those with diabetes, may have an atypical presentation without classic anginal symptoms. †

DIAGNOSTIC TESTS & INTERPRETATION


Initial Tests (lab, imaging)
  • 12-lead ECG (1)[A]: applies to both UA and NSTEMI
    • 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- to 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 to 6 hours after onset of ischemic symptoms but can be delayed from 8 to 12 hours (troponin T is not specific in patients with renal dysfunction).
    • With contemporary troponin assays, CK-MB and myoglobin are not useful in the diagnosis of ACS (3)[A].
    • Patients with negative biomarkers within 6 hours of the onset of symptoms should have biomarkers remeasured 8 to 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, β-blockers, and aldosterone antagonists.
  • Fasting lipid profile, preferably within 24 hours
  • Complete blood count (CBC), basic metabolic panel, activated partial thromboplastin time (aPTT)
  • Other laboratory tests:
    • Lactate dehydrogenase: increases within 24 hours, peaks 3 to 6 days, baseline 8 to 12 days (not routinely ordered)
    • Leukocytes: increase within several hours after MI, peak in 2 to 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"Ě)
  • 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 ACS 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, β-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, non-enteric-coated, initial dose of 162 to 325 mg PO or chewed to all patients (1)[A]
  • P2Y12 Inhibitors
    • Clopidogrel, loading dose 300 to 600 mg followed by 75 mg/day (1)[B]; or ticagrelor, loading dose 180 mg followed by 90 mg BID (1)[B]. Clopidogrel is favored in patients with ≥2-degree heart block, hemoglobin <10 g/dL, platelet count <100,000 cell/mm3, or liver disease.
    • Prasugrel is reserved for post-PCI patients treated with coronary stents, no history of stroke or TIA, <75 years, and weight >60 kg (1)[B].
    • Patients unable to take aspirin should receive a loading and maintenance dose of clopidogrel, ticagrelor, or prasugrel.
  • Nitroglycerin (NTG) sublingual 0.4 mg every 5 minutes for total of three doses, then assess need for intravenous (IV) NTG (1)[C].
  • Supplemental oxygen 2 to 4 L/min, maintaining arterial oxygen saturation >90% (1)[B]
  • Morphine sulfate 2 to 4 mg IV (with increments of 2 to 8 mg IV repeated at 5- to 15-minute intervals) (1)[A]
  • Oral β-blocker in patients without signs of heart failure, cardiogenic shock, or other contraindications (1)[B]. (IV β-blockers are potentially harmful when risk factors for shock are present.)
  • In patients with concomitant ACS, stabilized heart failure, and reduced systolic function (LVEF <40%), the recommended β-blockers are metoprolol succinate, carvedilol, and bisoprolol (1)[C].
  • Lipid-lowering therapy: initiate or continue high-intensity statin therapy (preferred due to nonlipid benefit on vascular function) (1)[A]; niacin or fibrate (1)[C] if statin use not possible
  • Risk stratify using the TIMI or GRACE score to select use of early invasive approach (within 12 to 24 hours of admission) versus ischemia-guided 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 to 12 months (2)[A]
    • 27% and 22% relative risk reduction in rates of MI at 6 to 12 months and 3 to 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).
  • Ischemia-guided therapy
    • 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 or ticagrelor (1)[B].
  • Contraindications: Prasugrel contraindicated in patients ≥75 years or those with history of CVA/TIA or increased bleeding risk. Ticagrelor contraindicated in ≥2-degree heart block.

Second Line
  • ACE inhibitor in patients with pulmonary congestion or left ventricular ejection fraction (EF) ‚ȧ40%. Substitute ARB for ACE-intolerant patients (1)[A].
  • Nondihydropyridine calcium channel blocker (CCB) (verapamil or diltiazem) to reduce myocardial oxygen demand when β-blockers are contraindicated if normal EF (1)[B]. Use oral long-acting CCB only after β-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]

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


  • It is reasonable in patients with possible ACS who have normal serial ECGs and cardiac troponins to have a treadmill ECG, stress myocardial perfusion imaging, or stress echocardiography before discharge or within 72 hours after discharge (2)[A],(3)
  • Follow up within 2 to 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


11 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. Circulation.  2013;127(23):e663-e828.22 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-e220.33 Amsterdam †EA, Wenger †NK, Brindis †RG, et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol.  2014;64(24):e139-e228. doi: 10.1016/j.jacc.2014.09.017.

ADDITIONAL READING


  • Cayla †G, Silvain †J, Collet †JP, et al. Updates and current recommendations for the management of patients with non-ST-elevation acute coronary syndromes: what it means for clinical practice. Am J Cardiol.  2015;115(Suppl 5):10A-22A.
  • 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.

CODES


ICD10


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

ICD9


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

SNOMED


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

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 to 7 days before elective CABG.
  • Do not use nitrate products in patients who recently used a phosphodiesterase-5 inhibitor (24 hours of sildenafil or vardenafil, or 48 hours of tadalafil).
  • Duration of antithrombotic therapy after NSTEMI depends on type of stent received and medications administered.
  • Avoid β-blockers in cocaine or methamphetamine user.
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