Unstable Angina, Non-St-Elevation Myocardial Infarction-Acute Coronary Syndrome

Talal T. Attar

Rebecca Miller

INTRODUCTION

Epidemiology

The 2020 Heart Disease and Stroke Statistics update of the American Heart Association (AHA) has reported that in the United States the prevalence of coronary heart disease (CHD) is 6.7% in persons 20 years of age or older. The prevalence of myocardial infarction (MI) is 3.0% in that population, with an MI every 40 seconds in the United States.

The median age at acute coronary syndrome (ACS) presentation is 65.6 years in males and 72 years in females.

PATHOGENESIS

ACS is the result of a sudden imbalance between myocardial oxygen consumption (MVO₂) and demand. Coronary artery obstruction caused by atherosclerotic lesions is the most common cause of such imbalance. In the acute phase, the obstruction and the associated myocardial ischemia are caused by plaque rupture with superimposed obstructive thrombus. They can also be caused by hemorrhage inside the plaque core. Distal embolization from the ruptured plaque and the associated thrombus can also cause microvascular obstruction, resulting in myocardial ischemia or necrosis.

CLINICAL PRESENTATION

ACS, usually caused by sudden reduction in coronary blood flow, is a clinical term that encompasses a spectrum of presentations associated with acute myocardial ischemia. The classic presenting symptom of ACS is anginal chest pain. A dull, deep, ill-defined discomfort is felt in the substernal region with common radiation to the left arm. At times, the symptoms could be atypical with either unusual location of the pain (neck, back, epigastric region, etc) or the chest pain is replaced with “angina-equivalent” symptoms. These symptoms could be cardiovascular such as dyspnea, or at times can mimic gastric symptoms such as nausea and epigastric burning.

With clinically suggestive symptoms, electrocardiographic (ECG) findings divide ACS syndromes. With the presence of ST elevation, the presentation is characterized as ST-elevation myocardial infarction (STEMI). In the presence of ST depression, transient ST elevation, or T-wave inversion, the presentation is characterized as unstable angina (UA) or non-ST-elevation myocardial infarction (NSTE-ACS). A key branch point between those two syndromes is the presence of elevated cardiac biomarkers.

A normal ECG and negative cardiac biomarkers do not completely exclude an ischemic etiology if the clinical features of the presentation are highly suggestive. Such a scenario is classified as UA.

DIAGNOSIS

History and Symptoms

A detailed history will help clinicians determine the likelihood that the main complaint and the associated symptoms are suggestive of ischemic presentation. The most common presenting symptom for ACS is chest pain. The typical ischemic pain is usually a deep, poorly defined, pressure-type chest pain in the substernal area with occasional radiation to the left arm. Common associated symptoms are dyspnea, diaphoresis, palpitations, dizziness, and syncope.

Atypical characteristics, location, and associated symptoms will decrease the likelihood of ischemic etiology, but does not completely exclude the diagnosis. Atypical locations of the pain include the neck, the mandible, shoulders, the periscapular area, upper back, and the epigastric region. Atypical characteristics of the pain include pleuritic stabbing pain. Pain localized to the tip of one finger, inducible with movement, palpation, and deep inspiration, or a brief duration of a few seconds is less likely ischemic. Atypical symptoms include nausea, vomiting, indigestion, and increased dyspnea without pain.

Some elements in the history that increase the probability of ACS include older age, male sex, diabetes, peripheral vascular disease, prior history of coronary artery disease (CAD), MI, or prior revascularization.

The relief of symptoms with nitroglycerin or gastrointestinal cocktails is not predictive of likelihood of ACS.³

Physical Examination

The physical examination in ACS could be normal. The presence of S4 or paradoxical splitting of S2 are nonspecific potential findings. Physical findings of left ventricular (LV) dysfunction such as S3 gallop, rales, or murmurs suggestive of acute mitral regurgitation also could be present, but nonspecific to the presentation and diagnosis of ACS.

Physical examination is also helpful in identifying findings suggestive of alternative diagnosis for the presenting symptoms. A pericardial rub in pericarditis, a blood pressure and pulse differential between extremities in acute aortic dissection, or a pulsatile mass with abdominal bruit in aortic aneurysm are a few examples.

Occasionally, findings of physical examination can impact therapeutic decisions. A focal neurologic deficit on neurologic examination, or evidence of occult blood on rectal examination, for example, will be implications for anticoagulation decisions in the management of ACS.

Electrocardiogram

A normal ECG at initial presentation with symptoms suggestive of ACS does not completely exclude this diagnosis. Of the patients with normal initial ECG, 1% to 6% will have an MI. Four percent will have UA.⁴,⁵,⁶

Given the fact that ECG changes could be dynamic, ECG should be repeated at 15- to 30- minute intervals during the first hour after presentation, especially if symptoms recur. Having a previous ECG for comparison is also beneficial, especially when the changes are nondynamic or nonspecific.

Diagnostic ECG findings include horizontal ST depression (>1 mm), transient ST elevation, and T-wave inversion. ST depression (<1 mm) and T-wave inversions (<2 mm) are nonspecific findings. Other causes for ECG changes that resemble ischemic abnormalities include LV hypertrophy, pericarditis, and electrolyte imbalances. Repolarization abnormalities, left bundle branch block, and paced rhythm can mask ischemia.

Cardiac Biomarkers

Cardiac biomarkers are essential to the diagnosis and stratification of patients with suspected ACS. As troponin I and T are cardiac-specific biomarkers present in high concentrations in cardiac tissue, but largely absent in nonmyocardial tissues, they are highly sensitive biomarkers for myocardial injury.⁷ High-sensitivity cardiac troponin T (hs-cTnT) and high-sensitivity cardiac troponin I (hs-cTnI) have similar diagnostic sensitivity, but hs-cTnT appears to have greater prognostic accuracy.⁸

Troponin levels should be evaluated at the time of presentation as well as 3 to 6 hours after onset of symptoms in patients with suspected UA or NSTE-ACS. Troponin levels greater than the 99th percentile of the upper reference limit in a healthy population are indicative of myocardial necrosis.⁷,⁸

Additional causes of troponin elevation include hypertension, myocardial trauma, myocarditis, pulmonary embolism, critical illness, renal dysfunction, and burns.⁷,⁸ As such, elevated troponin levels alone are indicative of myocardial necrosis that is the result of a nonthrombotic condition causing an imbalance between coronary oxygen supply and demand (ie, type 2 MI). To meet the definition of type 2 MI, in addition to elevated cardiac biomarkers, at least one of the following must be present:⁹

Symptoms of acute myocardial ischemia
New ischemic ECG changes
Development of pathologic Q waves
Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in a pattern consistent with an ischemic etiology

Other biomarkers such as creatine kinase-MB and myoglobin have been previously used in the diagnosis of ACS, but are less sensitive than is troponin in the detection of myocardial necrosis.

Diagnostic Imaging

A chest roentgenogram should be part of the initial evaluation of patients presenting with chest pain and suspected ACS. It can identify potential noncardiac etiology of the symptoms including pulmonary abnormalities. A widening mediastinum can suggest the diagnosis of aortic dissection.

If an intrathoracic etiology of symptoms is suspected, computed tomography is very useful, and could be incorporated with the initial evaluation process.

Transthoracic echocardiography can be helpful in detecting regional wall motion abnormalities. It is also the test of choice in identifying pericardial effusions and potential tamponade physiology.

Coronary computed tomography angiogram (CCTA) may be an option in patients with low-to-moderate clinical likelihood of UA because a normal scan excludes CAD. CCTA has a high negative predictive value (NPV) to exclude ACS.¹⁰

Risk Stratification

Early risk stratification is helpful in guiding the care path for the patient from the time of presentation. Triage decisions including appropriate placement could be optimized using risk stratification. The risk-benefit balance for early initiation of some therapy with significant potential side effects such as anticoagulation is based on patient risk assessment.

Clinical risk scores are also critical to the decision of pursuing an early invasive strategy versus a more conservative ischemia-guided approach for patients with NSTE-ACS and UA.

The thrombolysis in myocardial infarction (TIMI) risk score is composed of seven 1-point risk indicators rated on presentation.¹¹ A score of (0-1) is considered low. The composite endpoints increase as the score increases. The TIMI risk score has been validated internally within the TIMI 11B trial and in two separate cohorts of patients from the ESSENCE (Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Event) trial.¹² The TIMI risk score calculator is available at www.timi.org/index.php?page=riskUA-NSTEMI

The TIMI risk index is useful in predicting 30-day and 1-year mortality in patients with NSTE-ACS¹³ (Table 5.1).

The Global Registry of Acute Coronary Events (GRACE) risk model predicts in-hospital and postdischarge mortality or MI (Table 5.2).¹⁴,¹⁵,¹⁶,¹⁷ The GRACE tool was developed from 11,389 patients in GRACE and validated in subsequent GRACE and GUSTO IIb (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary
Arteries) cohorts. The sum of the scores is applied to a reference nomogram to determine all-cause mortality from hospital discharge to 6 months. A GRACE score of less than 109 is considered low and is available at: www.outcomes-umassmed.org/grace/acs_risk2/index.html

TABLE 5.1 TIMI Risk Score for NSTE-ACS

Present on Admission	Points
Age older than 65	1
Greater than three risk factors for coronary artery disease	1
Prior coronary artery disease	1
ST elevation on ECG	1
Greater than two angina events in the past 24 hours	1
Use of aspirin in the past 7 days	1
Elevated cardiac biomarkers	1
TOTAL POINTS	7 possible
ECG, electrocardiogram; NSTE-ACS, non-ST-elevation myocardial infarction-acute coronary syndrome; TIMI, thrombolysis in myocardial infarction.

MANAGEMENT

Antianginal Therapy

Oxygen

Supplemental oxygen therapy should be administered to patients presenting with possible UA or NSTE-ACS with oxygen saturation below 90% or in respiratory distress.⁷,⁸ There is no evidence to support supplemental oxygen therapy in all patients with UA or NSTE-ACS because it may increase coronary vascular resistance and increase the risk of mortality in those without hypoxemia.⁷,¹⁸

Nitrates

Nitroglycerin reduces cardiac oxygen demand by primarily reducing cardiac preload, modestly reducing afterload, dilating coronary arteries, and increasing collateral blood flow to ischemic myocardial tissue. Sublingual nitroglycerin (0.3-0.4 mg) should be administered every 5 minutes for up to three doses in patients with continued ischemic pain.⁷ Nitroglycerin infusion is appropriate for patients with refractory ischemic symptoms, heart failure, or hypertension. Nitrate therapy is contraindicated within 24 hours of sildenafil or vardenafil administration or within 48 hours of tadalafil administration because of the risk of severe hypotension.⁷,⁸ Patients with right ventricular infarction may develop severe hypotension following the administration of nitroglycerin or other agents that reduce preload, so its use is contraindicated in such patients.⁷

Analgesics

Morphine is an opioid commonly used to alleviate acute or chronic pain; in the setting of UA or NSTE-ACS, morphine is a venodilator and can modestly reduce systolic blood pressure and heart rate by increasing vagal tone.⁷ Morphine (1-5 mg) may be given intravenously every 5 to 30 minutes as needed for chest pain refractory to nitrates and beta-blockers, but empiric use of morphine in all patients with ACS is associated with worse clinical outcomes and impaired absorption of oral antiplatelet medications.⁷,¹⁹ Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen, and celecoxib interfere with the antiplatelet activity of aspirin, and are associated with an increased risk of major adverse cardiovascular outcomes and should be avoided in patients with NSTE-ACS.⁷,²⁰,²¹

TABLE 5.2 Global Registry of Acute Coronary Events (GRACE) Risk Calculator

GRACE Risk Model

Killip class

III

Systolic blood pressure

<80

80-99

100-119

120-139

140-159

160-199

>200

Heart rate

<60

60-69

70-89

90-109

110-149

150-199

>200

Age

<30

30-39

40-49

50-59

60-69

70-79

80-89

>90

100

Creatinine level

0-0.39

0.4-0.79

0.8-1.19

1.2-1.59

1.6-1.99

2.00-3.99

Cardiac arrest on admission

Present

Absent

ST-segment deviation

Present

Absent

Elevated cardiac biomarkers

Present

Absent

TOTAL POINTS

Beta-blockers

Beta-blockers prevent sympathetic activation of beta-receptors in the myocardium, thus reducing heart rate, contractility, and blood pressure, and, subsequently, myocardial oxygen consumption. An oral beta-blocker should be initiated within 24 hours of presentation, provided there are no signs of heart failure or reduced cardiac output, increased risk of cardiogenic shock (age older than 70 years, heart rate >110 beats per minute, systolic pressure <120 mm Hg, late presentation after symptom onset), or other contraindications to beta-blocker therapy.⁷,⁸,²² Beta-blocker therapy is associated with reductions in cardiac ischemia, reinfarction, and ventricular arrhythmias, as well as increased long-term survival.⁷,⁸,²³

Calcium Channel Blockers

Verapamil and diltiazem are non-dihydropyridine (non-DHP) calcium channel blockers that relax coronary vascular smooth muscle and reduce heart rate and blood pressure, thus increasing myocardial oxygen delivery and reducing myocardial oxygen demand. Oral non-DHP calcium channel blockers are recommended when beta-blockers are unsuccessful in relieving myocardial ischemia, contraindicated, or cause intolerable side effects.⁷

Ranolazine

Ranolazine reduces ventricular tension and myocardial oxygen consumption with minimal effect on blood pressure and heart rate. Ranolazine is approved for treatment of chronic angina, and the MERLIN-TIMI (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes-Thrombosis in Myocardial Infarction) 36 trial failed to demonstrate statistically significant reduction in major cardiovascular events in patients with ACS.²⁴

Anticoagulant Therapy

Anticoagulants inhibit thrombin generation and activity, and have been shown to reduce ischemic outcomes in NSTE-ACS.⁷ Anticoagulation is recommended for all patients presenting with NSTE-ACS, regardless of initial treatment strategy, unless contraindicated.¹⁹

Unfractionated Heparin

Unfractionated heparin (UFH) enhances the activity of anti-thrombin III, inactivating thrombin and preventing the conversion of fibrinogen to fibrin. The anticoagulant effect and pharmacokinetics of UFH varies widely between patients.⁸ Weight-based dosing provides more consistent anticoagulation than fixed dosing of UFH.⁷ UFH is dosed as a 60 IU/kg bolus (up to 4000 IU) followed by 12 IU/kg/hour infusion (up to 1000 IU/hour) for 48 hours or until coronary angiography or percutaneous coronary intervention (PCI) is performed.⁷,⁸

Only gold members can continue reading. Log In or Register to continue