Acute Coronary Syndrome

Practice Essentials

Acute coronary syndrome (ACS) refers to a spectrum of clinical presentations ranging from those for ST-segment elevation myocardial infarction (STEMI) to presentations found in non–ST-segment elevation myocardial infarction (NSTEMI) or in unstable angina. It is almost always associated with rupture of an atherosclerotic plaque and partial or complete thrombosis of the infarct-related artery.

Essential update: Discharge safe in suspected ACS if troponin and copeptin are negative

Patients with suspected ACS who test negative for troponin and copeptin can be safely discharged from the hospital without further testing, according to a recent study, the Biomarkers in Cardiology 8 (BiC-8) trial. Copeptin, a marker of severe hemodynamic stress, can be detected immediately in acute myocardial infarction.[1]

The study involved 902 patients at low to intermediate risk of ACS; half of the patients were treated with standard care, and the other 451 patients underwent a copeptin assay. In the latter group, patients with a positive copeptin test, defined as a level of 10 pmol/L or greater, were treated with standard ACS care, while patients with a copeptin level below 10 pmol/L were discharged into ambulant care, including an outpatient visit within 72 hours.

In the 451 patients tested for troponin and treated with standard care, the 30-day rate of major adverse cardiovascular events was 5.5%, compared with 5.46% in the 451 patients tested for troponin and copeptin, a statistically insignificant difference.

Signs and symptoms

Atherosclerosis is the primary cause of ACS, with most cases occurring from the disruption of a previously nonsevere lesion. Complaints reported by patients with ACS include the following:

PalpitationsPain, which is usually described as pressure, squeezing, or a burning sensation across the precordium and may radiate to the neck, shoulder, jaw, back, upper abdomen, or either arm Exertional dyspnea that resolves with pain or restDiaphoresis from sympathetic dischargeNausea from vagal stimulationDecreased exercise tolerance

Physical findings can range from normal to any of the following:

Hypotension: Indicates ventricular dysfunction due to myocardial ischemia, myocardial infarction (MI), or acute valvular dysfunctionHypertension: May precipitate angina or reflect elevated catecholamine levels due to anxiety or to exogenous sympathomimetic stimulation DiaphoresisPulmonary edema and other signs of left heart failureExtracardiac vascular diseaseJugular venous distentionCool, clammy skin and diaphoresis in patients with cardiogenic shockA third heart sound (S3) and, frequently, a fourth heart sound (S4)A systolic murmur related to dynamic obstruction of the left ventricular outflow tractRales on pulmonary examination (suggestive of left ventricular dysfunction or mitral regurgitation)

Potential complications include the following:

Ischemia: Pulmonary edemaMyocardial infarction: Rupture of the papillary muscle, left ventricular free wall, and ventricular septum

See Clinical Presentation for more detail.

Diagnosis

Guidelines for the management of non-ST-segment elevation ACS were released in 2011 by the European Society of Cardiology (ESC).[2] The guidelines include the use of the CRUSADE risk score (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines).

In the emergency setting, electrocardiography (ECG) is the most important diagnostic test for angina. ECG changes that may be seen during anginal episodes include the following:

Transient ST-segment elevationsDynamic T-wave changes: Inversions, normalizations, or hyperacute changesST depressions: These may be junctional, downsloping, or horizontal

Laboratory studies that may be helpful include the following:

Creatine kinase isoenzyme MB (CK-MB) levelsCardiac troponin levelsMyoglobin levelsComplete blood countBasic metabolic panel

Diagnostic imaging modalities that may be useful include the following:

Chest radiographyEchocardiographyMyocardial perfusion imagingCardiac angiographyComputed tomography, including CT coronary angiography and CT coronary artery calcium scoring

See Workup for more detail.

Management

Initial therapy focuses on the following:

Stabilizing the patient’s conditionRelieving ischemic painProviding antithrombotic therapy

Pharmacologic anti-ischemic therapy includes the following:

Nitrates (for symptomatic relief)Beta blockers (eg, metoprolol): These are indicated in all patients unless contraindicated

Pharmacologic antithrombotic therapy includes the following:

AspirinClopidogrelPrasugrelTicagrelorGlycoprotein IIb/IIIa receptor antagonists (abciximab, eptifibatide, tirofiban)

Pharmacologic anticoagulant therapy includes the following:

Unfractionated heparin (UFH)Low-molecular-weight heparin (LMWH; dalteparin, nadroparin, enoxaparin)Factor Xa inhibitors (rivaroxaban, fondaparinux)

Additional therapeutic measures that may be indicated include the following:

ThrombolysisPercutaneous coronary intervention (preferred treatment for ST-elevation MI)

Current guidelines for patients with moderate- or high-risk ACS include the following:

Early invasive approachConcomitant antithrombotic therapy, including aspirin and clopidogrel, as well as UFH or LMWH

See Treatment and Medication for more detail.

Image libraryA 62-year-old woman with a history of chronic stable angina and a "valve problem" presents with new chest pain. She is symptomatic on arrival, complaining of shortness of breath and precordial chest tightness. Her initial vital signs are blood pressure = 140/90 mm Hg and heart rate = 98. Her electrocardiogram (ECG) is as shown. She is given nitroglycerin sublingually, and her pressure decreases to 80/palpation. Right ventricular ischemia should be considered in this patient. NextBackground

Acute coronary syndrome (ACS) refers to a spectrum of clinical presentations ranging from those for ST-segment elevation myocardial infarction (STEMI) to presentations found in non–ST-segment elevation myocardial infarction (NSTEMI) or in unstable angina. In terms of pathology, ACS is almost always associated with rupture of an atherosclerotic plaque and partial or complete thrombosis of the infarct-related artery. (See Etiology.)

In some instances, however, stable coronary artery disease (CAD) may result in ACS in the absence of plaque rupture and thrombosis, when physiologic stress (eg, trauma, blood loss, anemia, infection, tachyarrhythmia) increases demands on the heart. The diagnosis of acute myocardial infarction in this setting requires a finding of the typical rise and fall of biochemical markers of myocardial necrosis in addition to at least 1 of the following[3] (See Workup.):

Ischemic symptomsDevelopment of pathologic Q wavesIschemic ST-segment changes on electrocardiogram (ECG) or in the setting of a coronary intervention

The terms transmural and nontransmural (subendocardial) myocardial infarction are no longer used because ECG findings in patients with this condition are not closely correlated with pathologic changes in the myocardium. Therefore, a transmural infarct may occur in the absence of Q waves on ECGs, and many Q-wave myocardial infarctions may be subendocardial, as noted on pathologic examination. Because elevation of the ST segment during ACS is correlated with coronary occlusion and because it affects the choice of therapy (urgent reperfusion therapy), ACS-related myocardial infarction should be designated STEMI or NSTEMI. (See Workup.)

Attention to the underlying mechanisms of ischemia is important when managing ACS. A simple predictor of demand is rate-pressure product, which can be lowered by beta blockers (eg, metoprolol or atenolol) and pain/stress relievers (eg, morphine), while supply may be improved by oxygen, adequate hematocrit, blood thinners (eg, heparin, IIb/IIIa agents such as abciximab, eptifibatide, tirofiban, or thrombolytics), and/or vasodilators (eg, nitrates, amlodipine). (See Medications.)

In 2010, the American Heart Association (AHA) published new guideline recommendations for the diagnosis and treatment of ACS.[4]

PreviousNextEtiology

Acute coronary syndrome (ACS) is caused primarily by atherosclerosis. Most cases of ACS occur from disruption of a previously nonsevere lesion (an atherosclerotic lesion that was previously hemodynamically insignificant yet vulnerable to rupture). The vulnerable plaque is typified by a large lipid pool, numerous inflammatory cells, and a thin, fibrous cap.

Elevated demand can produce ACS in the presence of a high-grade fixed coronary obstruction, due to increased myocardial oxygen and nutrition requirements, such as those resulting from exertion, emotional stress, or physiologic stress (eg, from dehydration, blood loss, hypotension, infection, thyrotoxicosis, or surgery).

ACS without elevation in demand requires a new impairment in supply, typically due to thrombosis and/or plaque hemorrhage.

The major trigger for coronary thrombosis is considered to be plaque rupture caused by the dissolution of the fibrous cap, the dissolution itself being the result of the release of metalloproteinases (collagenases) from activated inflammatory cells. This event is followed by platelet activation and aggregation, activation of the coagulation pathway, and vasoconstriction. This process culminates in coronary intraluminal thrombosis and variable degrees of vascular occlusion. Distal embolization may occur. The severity and duration of coronary arterial obstruction, the volume of myocardium affected, the level of demand on the heart, and the ability of the rest of the heart to compensate are major determinants of a patient's clinical presentation and outcome. (Anemia and hypoxemia can precipitate myocardial ischemia in the absence of severe reduction in coronary artery blood flow.)

A syndrome consisting of chest pain, ischemic ST-segment and T-wave changes, elevated levels of biomarkers of myocyte injury, and transient left ventricular apical ballooning (takotsubo syndrome) has been shown to occur in the absence of clinical CAD, after emotional or physical stress. The etiology of this syndrome is not well understood but is thought to relate to a surge of catechol stress hormones and/or high sensitivity to those hormones.

PreviousNextPrognosis

Six-month mortality rates in the Global Registry of Acute Coronary Events (GRACE) were 13% for patients with NSTEMI ACS and 8% for those with unstable angina.

An elevated level of troponin (a type of regulatory protein found in skeletal and cardiac muscle) permits risk stratification of patients with ACS and identifies patients at high risk for adverse cardiac events (ie, myocardial infarction, death) up to 6 months after the index event.[5, 6] (See Workup.)

The PROVE IT-TIMI trial found that after ACS, a J-shaped or U-shaped curve association is observed between BP and the risk of future cardiovascular events.[7]

LeLeiko et al determined that serum choline and free F(2)-isoprostane are also predictors of cardiac events in ACS. The authors evaluated the prognostic value of vascular inflammation and oxidative stress biomarkers in patients with ACS to determine their role in predicting 30-day clinical outcomes. Serum F(2)-isoprostane had an optimal cutoff level of 124.5 pg/mL, and serum choline had a cutoff level of 30.5 µmol/L. Choline and F(2)-isoprostane had a positive predictive value of 44% and 57% and a negative predictive value of 89% and 90%, respectively.[8]

Testosterone deficiency is common in patients with coronary disease and has a significant negative impact on mortality. Further study is needed to assess the effect of treatment on survival.[9]

A study by Sanchis et al suggests renal dysfunction, dementia, peripheral artery disease, previous heart failure, and previous myocardial infarction are the comorbid conditions that predict mortality in NSTEMI ACS.[10] In patients with comorbid conditions, the highest risk period was in the first weeks after NSTEMI ACS. In-hospital management of patients with comorbid conditions merits further investigation.

Patients with end-stage renal disease often develop ACS, and little is known about the natural history of ACS in patients receiving dialysis. Gurm et al examined the presentation, management, and outcomes of patients with ACS who received dialysis before presentation for an ACS. These patients were enrolled in the Global Registry of Acute Coronary Events (GRACE) at 123 hospitals in 14 countries from 1999-2007.

NSTEMI ACS was the most common in patients receiving dialysis, occurring in 50% of patients (290 of 579) versus 33% (17,955 of 54,610) of those not receiving dialysis The in-hospital mortality rates were higher among patients receiving dialysis (12% vs 4.8%; p [11]

In a study that assessed the impact of prehospital time on STEMI outcome, Chughatai et al suggest that “total time to treatment” should be used as a core measure instead of “door-to-balloon time.”[12] This is because on-scene time was the biggest fraction of "pre-hospital time.” The study compared groups with total time to treatment of more than 120 minutes compared with 120 minutes or less and found mortalities were 4 compared with 0 and transfers to a tertiary care facility were 3 compared with 1, respectively.

PreviousNextPatient Education

Patient education of risk factors is important, but more attention is needed regarding delays in door-to-balloon time, and one major barrier to improving this delay is patient education regarding his or her symptoms. Lack of recognition of symptoms may cause tremendous delays in seeking medical attention.

Educate patients about the dangers of cigarette smoking, a major risk factor for coronary artery disease (CAD). The risk of recurrent coronary events decreases 50% at 1 year after smoking cessation. Provide all patients who smoke with guidance, education, and support to avoid smoking. Smoking-cessation classes should be offered to help patients avoid smoking after a myocardial infarction. Bupropion increases the likelihood of successful smoking cessation.

Diet plays an important role in the development of CAD. Therefore, prior to hospital discharge, a patient who has had a myocardial infarction should be evaluated by a dietitian. Patients should be informed about the benefits of a low-cholesterol, low-salt diet. In addition, educate patients about AHA dietary guidelines regarding a low-fat, low-cholesterol diet.

A cardiac rehabilitation program after discharge may reinforce education and enhance compliance.

The following mnemonic may useful in educating patients with CAD regarding treatments and lifestyle changes necessitated by their condition:

A = Aspirin and antianginalsB = Beta blockers and blood pressure (BP)C = Cholesterol and cigarettesD = Diet and diabetesE = Exercise and education

For patients being discharged home, emphasize the following:

Timely follow-up with primary care providerCompliance with discharge medications, specifically aspirin and other medications used to control symptomsNeed to return to the ED for any change in frequency or severity of symptomsPreviousProceed to Clinical Presentation , Acute Coronary Syndrome