Non-ST Elevation Myocardial Infarction (NSTEMI) and
Unstable Angina (UA): 2012 Review
(More 2012 Topic Updates)
From concise clinical reviews by the don of cardiovascular disease, Eugene Braunwald (Harvard) in the May AJRCCM (Blue Journal) and Jeff Trost (Johns Hopkins) in Critical Care Medicine. These review articles on the diagnosis and treatment of non-ST-elevation acute coronary syndrome or NSTE-ACS (NSTE-myocardial infarction and unstable angina) are a great update, even if you’re comfortable treating MIs. Authors’ main recommendations follow.
Pathogenesis of NSTEMI/UA
At least three pathogenetic processes may result in NSTEMI/UA (what Braunwald calls NSTE-acute coronary syndrome or NSTE-ACS):
- Rupture of an unstable atherosclerotic plaque in a coronary artery;
- Coronary artery vasoconstriction;
- Oxygen supply/demand mismatch (increased O2 demand from sepsis or tachyarrhythmia, but a fixed coronary lesion limiting supply to the myocardium).
These are not mutually exclusive and can coexist in the same patient during a single episode of NSTEMI/UA.
Clinical Picture and Symptoms of NSTEMI/UA
Although the classic symptoms of retrosternal chest pain or pressure occurring at rest or with less-than-usual exertion are most common, painless “anginal equivalents” of dyspnea, abdominal pain, syncope, weakness, nausea, or heavy sweating may be the only symptoms. No particular guidance is offered to ascertain when these common symptoms might actually be a NSTEMI/UA — which adds helpful context for emergency physicians’ practice of ordering cardiac enzymes seemingly “on everybody.”
Diagnosis of NSTEMI
- Make sure it’s a NSTEMI, not an ST-elevation myocardial infarction (STEMI). NSTEMIs tend to have transient ST-segment depression >= 1 mm or T wave inversion in 2 or more contiguous precordial leads, accompanied by symptoms of chest pain, dyspnea, or significant ill-feeling. Cardiac enzymes (troponin and/or CK-MB) must be elevated, or else it’s unstable angina, not a myocardial infarction.
- STEMI must be considered if there are ST elevations in at least 2 contiguous precordial leads; a left bundle-branch block that’s new or of indeterminate tempo; or ST-depression in the right V1 and V2 precordial leads, suggesting a possible posterior infarct.
Troponin and other Cardiac Enzymes:
- Because troponin is so sensitive and not specific (renal failure, sepsis, strokes, severe hypertension, aortic dissection, and acute or chronic CHF can cause elevated troponins), elevation of cardiac enzymes alone is not diagnostic of a myocardial infarction/NSTEMI. Symptoms and/or ECG changes must also be present.
- At least 2 troponin samples, 6 to 9 hours apart, are required to rule out NSTEMI, according to Braunwald.
- Troponin remains elevated 1-2 weeks after an MI, so consider an old completed or resolving infarct when troponins are elevated.
- CK-MB falls to normal within 48 hours.
Echocardiography helps to determine contractile function, but wall motion abnormalities identified may be due to either acute ischemia or an old, resolved myocardial infarction. The same is true for nuclear perfusion imaging at rest during a possible NSTEMI/UA (areas of reduced perfusion may be new, or old).
CT-angiography shows promise as a tool in emergency departments in evaluation of chest pain, at least among patients considered to be at low risk for NSTEMI/UA. A 2007 randomized trial in JACC and a 2012 randomized trial in NEJM suggest that absence of significant stenosis on CTA can safely rule out ACS/NSTEMI/UA in low-to-intermediate-risk patients presenting to emergency departments with chest pain or other ACS symptoms.
Risk Stratification of NSTEMI/UA
- The critical question: Does the patient “need a cath,” i.e., might an early invasive percutaneous coronary intervention (PCI) improve her heart function or survival?
- Among “all comers” with NSTEMI or UA (NSTE-ACS), 85% have at least a 50% stenosis in one or more major coronary arteries (this does not imply the stenosis is acute, due to a plaque rupture). 20% have significant (>=50%) stenoses in 3 major coronary arteries.
- Risk stratify using an online calculator for the GRACE and / or TIMI risk models. A definite benefit from early cardiac catheterization has been shown in randomized trials for patients with a GRACE score >140, or who have 3+ TIMI risk factors.
Treatment of NSTEMI/UA
- Relieve angina with nitroglycerin (sublingual, then IV if necessary), morphine, beta-blockers, and/or calcium channel blockers (considered second-line). Avoid beta blockers in patients with decompensated heart failure, high AV block, hypotension, or who may have used cocaine.
- Continuous ECG monitoring is recommended for at least 48 hours to identify transient ST changes or frequent ventricular ectopy (suggestive of recurrent ischemia and elevated risk of sudden cardiac death, respectively). Anecdotally, if a patient has normal cardiac enzymes (unstable angina only), this recommendation seems unlikely to be followed in today’s revolving-door hospital system.
- Supplemental oxygen is only recommended for those with pulse oximetry saturation <90%, or with rales or heart failure, says Braunwald.
- Beta-blockers “may be initiated or continued in patients without severe heart failure, hypotension or atrioventricular block.” (Braunwald) This recommendation has softened since I trained – note the “may,” not “should,” and with no described evidence of benefit.
- Give antiplatelet therapy: aspirin (162-325 mg followed by 75-162 mg daily) and clopidogrel (Plavix). The new antiplatelet plasugrel (Effient) is even more powerful than Plavix and has a faster onset; in the U.S., plasugrel is only approved for patients getting percutaneous coronary intervention (stents / angioplasty). Effient may be more efficacious, but also has a significantly higher bleeding risk than Plavix.
- Give antithrombotic therapy: In patients being conservatively treated (no PCI/cath planned) who are at high risk of bleeding, fondaparinux is preferred (lower rate of major bleeding; low/no incidence of thrombocytopenia). Low-molecular weight heparin (enoxaparin/Lovenox) results in better outcomes than unfractionated heparin in patients being treated conservatively; in patients undergoing cath, Lovenox causes more major bleeding than UFH. Bivalirudin, a new direct thrombin inhibitor, has a low rate of bleeding in limited studies, and can be used instead of heparin for patients planned for PCI. Unfractionated heparin is still a good choice for for patients being planned for PCI.
- A GP IIb/IIIa inhibitor can be substituted for Plavix; adding a GP IIb/IIIa to the above therapies (including Plavix) might add benefit, but significantly increases bleeding risk.
Based on the ELISA, ISAR-COOL, OPTIMA, TIMACS, and ABOARD randomized trials, the following recommendations are made regarding an invasive catheterization (PCI/stenting) strategy for people with NSTEMI:
- A primary invasive strategy (cath within 72 hours) should be performed in anyone who is not at “low risk” for ischemic complications.
- Cath emergently (within 2 hours) should be done for people considered at very high risk of death from MI.
- Cath within 24 hours in those at high risk for complications in-hospital.
- Cath within 72 hours for those at low risk for an ischemic complication but who have an “indication” (it’s not specified what this might be, but probably ongoing chest pain would be one).
These all used soft or composite endpoints, but suggested a benefit for early invasive intervention for the described patients.
Braunwald E. Unstable Angina and Non–ST Elevation Myocardial Infarction. Concise Clinical Review. Am J Resp Crit Care Med 2012;185:924-932.
Trost JC, Lange RA. Treatment of acute coronary syndrome: Part 1: Non-ST-segment acute coronary syndrome. Crit Care Med 2011;39:2346-2353.