Diagnostic Tests in Acute Coronary Syndromes (ACS) and Acute Myocardial Infarction (AMI)
Diagnostic and Prognostic Test Characteristics of Signs and Symptoms of ACS/AMI
Signs and symptoms of ACS/AMI may be useful in combination with other important information (biomarkers, risk factors, electrocardiogram [ECG], and other diagnostic tests) in making triage and some treatment and investigational decisions in the out-of-hospital setting and the Emergency Department (ED). Signs and symptoms are not independently diagnostic of ACS/AMI.
Diagnostic and Prognostic Test Characteristics of Cardiac Biomarkers for ACS/AMI
Emergency physicians should obtain cardiac biomarkers for all patients with suspected ACS/AMI. Serial time points (increasing interval from onset of symptoms to testing), and multimarker strategies greatly improve sensitivity for detection of myocardial ischemia or infarction but are insensitive for ruling out these diagnoses in the out-of-hospital setting or within the first 4 to 6 hours of evaluation in the ED.
ED Interpretation of 12-Lead ECG for ST-Elevation Myocardial Infarction (STEMI)
Out-of-Hospital
Trained out-of-hospital personnel can accurately identify acute STEMI in prehospital 12-lead ECGs obtained in patients with ACS. The ECG is used in combination with chest pain symptoms, assessment of risk factors, and other diagnostic tests to rule out alternative diagnoses. Out-of-hospital interpretation of a single 12-lead ECG with stringent inclusion criteria (i.e., ST elevation >0.1 mV in 2 or more adjacent precordial leads or 2 or more adjacent limb leads and with reciprocal depression) has a high specificity for the diagnosis of STEMI.
ED
In the ED the interpretation of a single 12-lead ECG with rigid inclusion criteria (see above) is discriminating for the diagnosis of STEMI with a relatively low sensitivity but a high specificity for this diagnosis.
Acute Therapeutic Interventions
Adjunctive Therapies
Oxygen Therapy
Supplementary oxygen should be given to patients with arterial oxygen desaturation (arterial oxygen saturation [SaO2] <90%). Given the safety profile of oxygen in this population and the potential benefit in the patient with unrecognized hypoxia, it is reasonable to give supplementary oxygen to all patients with uncomplicated STEMI during the first 6 hours of emergency management.
Aspirin (Acetylsalicylic Acid)
It is reasonable for dispatchers to advise the patient with suspected ACS and without a true aspirin allergy to chew a single dose (160 to 325 mg) of aspirin (ASA). It is also reasonable for emergency medical services (EMS) providers to administer ASA because there is good evidence that it is safe and that the earlier ASA is given, the greater the reduction in risk of mortality. Limited evidence from several very small studies suggests that the bioavailability and pharmacologic action of other formulations of ASA (soluble, IV) may be as effective as chewed tablets.
Heparins
Unstable angina (UA)/Non-STEMI (NSTEMI). In the ED giving low-molecular-weight heparin (LMWH) instead of unfractionated heparin (UFH) in addition to aspirin to patients with UA/NSTEMI may be helpful. There is insufficient evidence to identify the optimal time for administration after onset of symptoms. In-hospital administration of UFH is recommended if reperfusion is planned within the first 24 to 36 hours after onset of symptoms. There is insufficient evidence to recommend for or against treatment with LMWH in UA/NSTEMI in the out-of-hospital setting. Changing from one form of heparin to another (crossover of antithrombin therapy) during an acute event is not recommended.
STEMI. LMWH is an acceptable alternative to UFH as ancillary therapy for patients with STEMI who are <75 years of age and receiving fibrinolytic therapy. LMWH should not be given if significant renal dysfunction (serum creatinine >2.5 mg/dL in men or 2 mg/dL in women) is present. UFH is recommended for patients >75 years of age as ancillary therapy to fibrinolysis. Heparin may be given to STEMI patients who do not receive reperfusion therapy. These include patients at high risk for cardioembolic events and those on prolonged bedrest. UFH or LMWH may be used. Patients receiving LMWH should have no significant renal dysfunction.
Clopidogrel
Give a 300-mg oral loading dose of clopidogrel in addition to standard care (ASA, heparin) to patients with ACS within 4 to 6 hours of contact if they have:
- A rise in serum cardiac biomarkers or new ECG changes consistent with ischemia when a medical approach or percutaneous coronary intervention (PCI) is planned in the absence of ST-segment elevation
- STEMI in patients up to 75 years of age receiving fibrinolysis, ASA, and heparin
Although in one large trial (Budaj et al., 2002) preoperative clopidogrel administration was associated with increased postoperative reoperation for bleeding, the recent CLARITY TIMI 28 trial (Sabatine et al., 2005) did not document increased bleeding in patients undergoing coronary artery bypass graft (CABG) within 5 to 7 days of receiving clopidogrel. Current American College of Cardiology/American Heart Association (ACC/AHA) recommendations (Antman et al., 2004) advise withholding clopidogrel for 5 to 7 days before planned CABG.
It is reasonable to give clopidogrel 300 mg orally to patients with suspected ACS (without ECG or cardiac marker changes) who have hypersensitivity to or gastrointestinal intolerance of ASA.
Glycoprotein (GP) IIb/IIIa Inhibitors
High-risk UA/NSTEMI. If revascularization therapy (PCI or surgery) is planned, it is safe to give GP IIb/IIIa inhibitors in addition to standard therapy (including ASA and heparin) to patients with high-risk UA/NSTEMI in the ED. This therapy may reduce the risk of death or recurrent ischemia. High-risk features of UA/NSTEMI are defined in the consensus on science statement in the original guideline document. If revascularization therapy is not planned, the recommendation for use of GP IIb/IIIa varies by drug. Tirofiban and eptifibatide may be used in patients with high-risk UA/NSTEMI in conjunction with ASA and LMWH if PCI is not planned. But abciximab can be harmful in patients with high-risk UA/NSTEMI if early (e.g., 24 hours) PCI is not planned.
STEMI. Abciximab is not currently recommended in patients receiving fibrinolytics for STEMI. In patients treated with PCI without fibrinolysis, abciximab may be helpful in reducing mortality rates and short-term reinfarction. There is no evidence documenting a better outcome by giving GP IIb/IIIa inhibitors out of hospital or early in the ED.
Reperfusion Strategies
Out-of-Hospital Fibrinolytics for STEMI
Out-of-hospital administration of fibrinolytics by paramedics, nurses, or physicians using an established protocol is safe and feasible for patients with STEMI and no contraindications. This requires adequate provisions for the diagnosis and treatment of STEMI and its complications, including strict treatment directives, fibrinolytic checklist, ECG acquisition and interpretation, defibrillators, experience in advanced cardiac life support (ACLS) protocols, and the ability to communicate with medical control. Physicians may give out-of-hospital fibrinolytics to patients with symptoms compatible with ACS and signs of true posterior infarctions (no ST elevation).
Fibrinolytics in the ED Management of STEMI
In the ED patients with symptoms of ACS and ECG evidence of either STEMI, (presumably) new left bundle branch block (LBBB), or true posterior infarction should be given fibrinolytics if fibrinolysis is the treatment of choice and there are no contraindications. The emergency physician should give fibrinolytics as early as possible according to a predetermined protocol.
Primary PCI Compared With ED or Out-of-Hospital Fibrinolysis
All patients presenting with STEMI within 12 hours of the onset of symptoms should be evaluated for reperfusion therapy (i.e., fibrinolysis or PCI).
Primary PCI is the preferred reperfusion strategy in STEMI with symptom duration >3 hours if a skilled team can perform primary PCI in <90 minutes after first medical contact with the patient or if there are contraindications to fibrinolysis.
If the duration of symptoms is <3 hours, treatment is more time-sensitive, and the superiority of out-of-hospital fibrinolysis, immediate in-hospital fibrinolysis, or transfer for primary PCI is not established (see below for recommendation concerning transfer).
Early revascularization (i.e., surgery, primary or early PCI, defined as PCI <24 hours after fibrinolysis) is reasonable in patients with cardiogenic shock, especially for patients <75 years of age.
Primary and Secondary Prevention Interventions
Antiarrhythmics
There is insufficient evidence to support the routine use of any antiarrhythmic drug as primary prophylaxis within the first 4 hours of proven or suspected AMI. This conclusion does not take into account the potential effect of beta-beta-blockers (see below).
Beta-Blockers
In the ED treat ACS patients promptly with IV beta-blockers followed by oral beta-blockers. Beta-blockers are given irrespective of the need for revascularization therapies. Contraindications to beta-blockers include hypotension, bradycardia, heart block, moderate to severe congestive heart failure, and reactive airway disease.
Angiotensin-Converting Enzyme (ACE) Inhibitors
Start an oral ACE inhibitor within 24 hours after onset of symptoms in patients with MI whether or not early reperfusion therapy is planned. Do not give an ACE inhibitor if the patient has hypotension (systolic blood pressure <100 mm Hg or more than 30 mm Hg below baseline) or if the patient has a known contraindication to these drugs. ACE inhibitors are most effective in patients with anterior infarction, pulmonary congestion, or left ventricular ejection fraction <40%.
There is no evidence to recommend for or against starting ACE inhibitors in the out-of-hospital setting. Avoid giving IV ACE inhibitors within the first 24 hours after onset of symptoms because they can cause significant hypotension during this phase.
HMG CoA (3-Hydroxy-3-Methylglutaryl-Coenzyme A) Reductase Inhibitors (Statins)
It is safe and feasible to start statin therapy early (within 24 hours) in patients with ACS or AMI; once started, continue statin therapy uninterrupted.
Healthcare System Interventions for ACS/AMI
12-Lead Out-of-Hospital ECG and Advance ED Notification
Routine use of the 12-lead out-of-hospital ECG with advance ED notification may benefit STEMI patients by reducing the time interval to fibrinolysis.
Advance ED notification may be achieved with direct transmission of the ECG itself or verbal report (via telephone) of the ECG interpretation by out-of-hospital personnel.
Interfacility Transfer for Primary PCI
For patients with STEMI presenting >3 hours but <12 hours from the onset of symptoms, interfacility transfer from hospitals that lack primary PCI capability to centers capable of providing primary PCI is indicated if such a transfer can be accomplished as soon as possible. Optimally PCI should occur <90 minutes from first medical contact (i.e., contact with a healthcare provider who can make the decision to treat or transfer).
In patients with STEMI presenting <3 hours from onset of symptoms, treatment is more time-sensitive, and there is inadequate data to indicate the superiority of out-of-hospital fibrinolysis, immediate hospital fibrinolysis, or transfer for primary PCI.
The time recommendations do not apply to patients in cardiogenic shock. In such patients the evidence supports early revascularization therapy (primary PCI, early PCI, or surgery) compared with medical therapy.
Out-of-Hospital Triage for PCI
There is some limited evidence to recommend out-of-hospital triage for primary PCI for patients with uncomplicated STEMI who are <60 minutes away from a PCI site in systems that use Mobile Intensive Care Unit (MICUs) with physicians on board with the proviso that the delay from decision to treat to balloon inflation is <90 minutes. Further studies are required to define appropriate triage and transport criteria.
Interfacility Transfer for Early PCI
There is inadequate evidence to recommend the routine transfer of patients for early PCI after successful fibrinolysis in community hospital EDs or out of hospital.
Transfer for early PCI is recommended as one strategy for early revascularization for patients with cardiogenic shock, especially patients <75 years of age; or with hemodynamic instability or persistent symptoms of ischemia after fibrinolysis.