Unstable Angina

Etiology

Coronary atherosclerotic disease is the underlying cause of unstable angina in nearly all patients with acute myocardial ischemia. The most common cause of unstable angina is due to coronary artery narrowing from a nonocclusive thrombus that develops on a disrupted atherosclerotic plaque. A less common cause is vasospasm of a coronary artery (eg, variant Prinzmetal angina). Endothelial or vascular smooth dysfunction causes this vasospasm (see Image. Types of Angina in the Coronary Artery).[4] 

Epidemiology

Coronary artery disease affects a large portion of the population. There is an estimation that coronary artery disease causes more than a third of deaths in people aged 35 and older; this condition is the leading cause of death in this particular age group. Roughly 18 million individuals in the United States alone are believed to be affected by this disease. The incidence is higher in men, but as individuals surpass 75, the incidence of men and women becomes similar. Other risk factors include:

• Obesity
• Diabetes
• Hypertension
• High cholesterol
• Smoking history
• Cocaine or amphetamine abuse
• Family history
• Chronic kidney disease
• Human immunodeficiency syndrome
• Autoimmune disorders
• Anemia [5] 

The mean age of presentation is 62, and women tend to be older than men at the time of presentation, while Black individuals tend to present at a younger age.

Pathophysiology

Unstable angina occurs when blood flow to the myocardium is obstructed, leading to inadequate perfusion. Blood supply to the heart begins in the aorta and flows into the coronary arteries, which branch into smaller vessels to nourish specific areas of the heart. The left coronary artery divides into the circumflex and left anterior descending arteries, while the right coronary artery splits into smaller branches. Unstable angina commonly results from intraluminal plaque formation, thrombosis, vasospasm, or elevated blood pressure. Frequently, a combination of these factors contributes to reduced blood flow, triggering symptoms of unstable angina. Factors that increase myocardial oxygen demand include:

• Arrhythmias
• Fever
• Hypertension
• Cocaine use
• Aortic stenosis
• Arteriovenous shunts
• Anemia
• Thyrotoxicosis
• Pheochromocytoma
• Congestive heart failure

History and Physical

Patients will often present with chest pain and shortness of breath. The chest pain will usually be described as pressure-like, although not necessarily limited to this description. Tightness, burning, and sharp types of pain can be defined. Often, patients will report discomfort as opposed to actual pain. The pain often radiates to the jaw or arms, affecting both the left and right sides. Constitutional symptoms such as nausea, vomiting, diaphoresis, dizziness, and palpitations may also be present. Exertion may worsen pain, and rest can ease the pain; nitroglycerin and aspirin administration may also improve the pain.

The exam will likely be standard, although the patient may be clutching at their chest, sweating, or have

labored breathing; their heart sounds may be tachycardic, and rales may be heard due to pulmonary edema. Findings suggestive of a high-risk situation include:

• Dyskinetic apex
• Elevated jugular venous pressure
• Presence of third or fourth heart sounds (S3 or S4)
• New apical systolic murmur
• The presence of rales and crackles
• Hypotension

Evaluation

When a patient presents, they should be evaluated quickly with an electrocardiogram (ECG) to assess for ischemic signs or possible STEMI. The ECG in unstable angina may show hyperacute T-wave, flattening of the T-waves, inverted T-waves, and ST depression. ST elevations indicate STEMI, and these patients should be treated with percutaneous coronary intervention or thrombolytics while they wait for the availability of a catheterization lab. Any arrhythmias may be present in acute coronary syndrome, including junctional rhythms, sinus tachycardia, ventricular tachycardia, ventricular fibrillation, and left bundle branch block. However, most commonly, the patient will be in sinus rhythm, especially in unstable angina, as opposed to infarcted tissue.

The history should be screened for other emergent causes of chest pain, shortness of breath, pulmonary embolism, aortic dissection, esophageal rupture, pneumonia, and pneumothorax. The patient should be kept on a cardiac monitor to evaluate for any rhythm changes. Further testing may include any number of cardiac stress tests (eg, walking treadmill stress test, stress echocardiogram, myocardial perfusion imaging, cardiac computed tomography/magnetic resonance imaging, or the gold standard—cardiac catheterization). These tests are typically ordered and performed by inpatient and primary care clinicians, but with the growth of observation medicine, emergency medicine clinicians may order these.[6][7]

Acute coronary syndrome risk assessment:

• Prior myocardial infarction or known history of coronary artery disease
• Transient ECG or hemodynamic changes during chest pain
• Chest, neck, or left arm with documented angina
• ST depression or elevation of more than 1 mm
• Marked symmetrical T-wave inversion

Treatment / Management

The mainstay of treatment focuses on improving perfusion of the coronary arteries, which can be performed in several ways.

Aspirin

Patients are often treated with aspirin for its antiplatelet therapies (162-325 mg orally or 300 mg rectally if the patient cannot swallow). The aspirin should be administered within 30 minutes.

Nitroglycerin

Nitroglycerin comes in several forms (intravenous, sublingual, transdermal, orally) and improves perfusion by vasodilating the coronaries, allowing improved blood flow and blood pressure. This decreases the amount of work the heart has to perform, which reduces its energy demand.

Clopidogrel 

Clopidogrel is an option for patients who cannot tolerate aspirin. Prasugrel is more effective than clopidogrel but is associated with a higher risk of bleeding. Recently, ticagrelor and aspirin have been approved to reduce the rate of thrombotic cardiac events.

Supplemental Oxygen

Supplemental oxygen should also be given via nasal cannula to maintain appropriate oxygen saturation. These 3 actions are the quickest and most important functions to evaluate and treat unstable angina. The patient's response should be assessed in patients with continued pain or longer recovery time because they are at much higher risk for myocardial infarction.

Other Therapies

Other potential therapies include:

• Heparin: Either low- or high-molecular-weight heparin for anticoagulation
• Beta-blockers: Can decrease the energy demand by reducing blood pressure and heart rate [1][8][9] 
• Ranolazine: Studied in patients with unstable angina; significant reduction in the endpoint of recurrent ischemia in the ranolazine group [10]
• Statins: Used in patients with unstable angina, validated by many trials
(A1)

Cardiac angiography is indicated in unstable angina if the patient has:

• Cardiogenic shock
• Depressed ejection fraction
• Angina refractory to pharmacological therapy
• New mitral regurgitation
• Unstable arrhythmias

Early percutaneous coronary intervention in non-STEMI (eg, within 6 hours) has been shown to have lower mortality than those who undergo delayed percutaneous coronary intervention.

Differential Diagnosis

The differential diagnoses for instable angina include the following:

• Aortic dissection
• Pericarditis
• Pneumothorax
• Pulmonary embolism
• Peptic ulcer disease

Prognosis

The critical complications of unstable angina include:

• Myocardial infarction 
• Stroke
• Death

Study results show that patients with new-onset ST-segment elevation (>1 mm) have a 12-month rate of myocardial infarction or death of about 11%, compared with only 7% for patients who only have isolated inversion of the T-wave.

Adverse prognostic factors include:

• Low ejection fraction
• Ongoing congestive heart failure 
• New or worsening mitral regurgitation
• Hemodynamic instability
• Sustained ventricular tachycardia
• Recurrent episodes of angina despite maximal therapy