Unstable angina

What is unstable angina?

Unstable angina is a clinical condition characterized by ischemic chest pain occurring at rest or with minimal exertion, rapid deterioration of previously stable angina (crescendo pattern – more severe, prolonged or frequent than previously), or new onset severe ischemic chest pain of less than one month’s duration.

 Pathophysiology:

Unstable angina is caused by an imbalance between myocardial (heat muscle) oxygen supply and demand. The main mechanism is rupture or erosion of an atherosclerotic plaque that triggers platelet aggregation and forms a non-occlusive thrombus in a coronary artery. This non-occlusive thrombus obstructs the coronary blood flow partially. As a result, heart muscle gets inadequate oxygen and produces severe ischemic chest pain.

Symptoms:

The cardinal symptom of unstable angina is chest pain, usually located in the center of the chest, but may radiates to the neck, jaw, left shoulder, back, and left arm. Pain is crushing or squeezing in character, persists more than 15 minutes and not relief by rest. Sometimes associated sweating, vomiting or breathing difficulty may also present.

Diagnosis:

Diagnosis of unstable angina is done by clinical symptoms with following investigations:

Electrocardiography (ECG)

ECG findings in unstable angina are variables. It may be normal, or may found ST-segment depression or T-wave inversion.

 

ECG findings of unstable angina

Figure: ECG of unstable angina
 

Cardiac markers

In unstable angina, cardiospecific isoenzyme CK-MB (creatine kinase myocardial band) level remains normal, but cardiospecific proteins troponin T and troponin I may be detectable in small amounts. Usually troponin T less than 0.01 ng/dL and troponin I less than 0.1 ng/dL are found. Patients with unstable angina who have elevated troponin, are at high risk for myocardial infarction or death.

Echocardiography

It uses sound waves to produce images of the heart. In unsable angina, ventricular wall motion defects may be found in echocardiography

Coronary angiography

Coronary angiography is an imaging technique. It is used to visualize the lumen of coronary arteries of the heart. It provides detailed information about the extent and nature of coronary artery occlusion.

Risk stratification:

Risk stratification is important in unstable angina. It helps in choosing appropriate treatment plan and also gives an idea about patient’s prognosis. Risk stratification can be made using the ECG findings, troponin level, TIMI score and GRACE score. GRACE score is the best for risk stratification because it is derived from multinational patients.

Risk stratification by ECG findings

Low risk groups:

  • Normal ECG
  • T-wave inversion less than 1 mm.

Medium risk groups:

  • ST-segment depression 1 mm or less.
  • T-wave inversion more than 1 mm.

High risk groups:

  • Transient ST-segment elevation.
  • ST-segment depression more than 1 mm.
  • Deep symmetrical T-wave inversion.

Risk stratification by troponin level (FRISC study)

Low risk groups:

Serum Troponin T level less than 0.06 µg/L

Medium risk groups:

Serum Troponin T level 0.06 – 0.18 µg/L

High risk groups:

Serum Troponin T level more than 0.18 µg/L

Complications:

1. The main complication of unstable angina relate to its tendency to progress to acute myocardial infarction.

2. Acute heart failure or cardiogenic shock may occur, if the ischemic territory is large.

3. Mitral regurgitation may develop, if papillary muscle ischemia present.

4. Heart arrhythmias may also occur in unstable angina.

5. Chronic heart failure may develop due to long term inadequate blood supply to heart muscle.

Treatment:

Low risk patients may be managed in a general medical unit. But medium and high risk patients should be managed in a coronary care unit.

(1) Initial management should include bed rest with continuous ECG monitoring, nitrates, and beta-blockers to provide relief and prevention of recurrence of chest pain.

Nitrates

Nitrates act as a vasodilator and relief pain. Nitrates should first be given buccally or by sublingual (under tongue) spray. If the patient experiencing persistent ischemic chest pain after 3 doses given 5 minutes apart, then intravenous glyceryl trinitrate 0.6-1.2 mg/hour or isosorbide dinitrate 1-2 mg/hour can be given until pain relieved or systolic blood pressure falls to less than 100 mgHg. Oral or sublingual nitrates can be used once the pain has resolved.

Beta-blockers

Beta-blockers reduce arrhythmias, heart rate, blood pressure and myocardial oxygen demand, and relive pain. Oral beta-blocker atenolol 25-50 mg twice daily, metoprolol 25-50 mg twice daily, or bisoprolol 5 mg once daily are usually adequate. Patients with heart rate more than 90 beats/minute or patients with hypertension (systolic blood pressure more than 150 mmHg or diastolic more than 90 mmHg), intravenous beta-blocker (atenolol 5-10 mg or metoprolol 5-15 mg over 5 minutes) can be given. Beta-blockers should be avoided if there is heart failure, heart block, hypotension, or bradycardia.

(2) Relief of pain by opiate analgegic, if pain not controlled with nitrate and beta-blocker:

Intravenous morphine 10 mg or diamorphine 5 mg is usually used and may have to be repeated to relieve severe pain.

(3) Antiplatelet therapy:

Antiplatelet drugs prevent platelet aggregation within coronary artery. A 300 mg tablet of aspirin should be given orally as early as possible then 75 mg daily should be continued indefinitely if there are no side effects occur. Aspirin reduces the mortality rate of unstable angina by approximately 25%. In combination of aspirin, clopidogrel 300 mg should be given orally as early as possible, followed by 75 mg daily thereafter, gives a further reduction in mortality. Ticagrelor 150 mg followed by 90 mg two times daily is more effective than clopidegrol. High risk patients, especially patients with diabetes mellitus or patients who undergo percutaneous coronary intervention (PCI), should also be considered for intake of glycoprotein IIb/IIIa receptor blocker (block the final common pathway of platelet aggregation), such as tirofiban, abciximab, or eptifibatide.

(4) Anticoagulant therapy:

Anticoagulant drugs prevent myocardial infarction, and reduces the risk of thromboembolic complications. Anticoagulation can be achieved by using unfractionated heparin, fractionated heparin (enoxaparin, dalteparin), or a pentasaccharide (fondaparinux). Comparatively fractionated heparin is more safety and efficacious than unfractionated heparin, and pentasaccharide is more safety and efficacious than fractionated heparin. The dose regimens are:

  • Enoxaparin: 1 mg/kg body weight two times daily usually for 8 days by subcutaneous injection.
  • Dalteparin: 120 units/kg body weight two times daily usually for 8 days by subcutaneous injection.
  • Fondaparinux: 2.5 mg daily usually for 8 days by subcutaneous injection.

(5) Statins:

Irrespective of serum cholesterol level, all patients with unstable angina should receive statin such as atovastatin, simvastatin,or rosuvastatin.

(6) Revascularization treatment:

Medium to high risk patients need revascularization treatment. Revascularization can be done either by PCI (percutaneous coronary intervention) or by CABG (coronary artery bypass grafting). Usually, PCI is recommended for one or two-vessel disease and CABG for left main coronary artery or severe three-vessel disease. Medical treatment is appropriate in low risk patients and revascularization is reserved for those who fail to settle with medical therapy.

Prognosis:

According to FRISC study, 5-month risk of death or myocardial infarction is 4.3% in low risk, 10.5% in medium risk and 16.1% in high risk patients. According to TIMI score, 14 days risk of death or myocardial infarction ˂ 8% in low risk, 8 to 20% in medium risk and ˃ 20% in high risk patients. According to GRACE score, in-hospital or one month mortality ˂ 1% in low risk, 1 to 9% in medium risk and ˃ 9% in high risk patients with unstable angina.