Angina Pectoris, Chronic Stable

Essentials of Diagnosis

• Precordial chest pain, usually precipitated by stress or exertion, and rapidly relieved by resting or nitrates

• ECG, echocardiographic, or scintigraphic evidence of ischemia during pain or stress testing

• Angiographic evidence of significant obstruction of major coronary vessels

General Considerations

• Usually due to atherosclerotic coronary artery disease

• Less common causes

  • Congenital anomalies

  • Emboli

  • Arteritis

  • Dissection

  • Severe myocardial hypertrophy

  • Severe aortic stenosis or regurgitation

• Commonly exacerbated by increased metabolic demands (eg, hyperthyroidism, anemia, tachycardias)

• Coronary vasospasm may occur at the site of a lesion or, less frequently, in apparently normal vessels spontaneously, or by exposure to cold, emotional stress, vasoconstricting medications, or cocaine

Demographics

• Underdiagnosed in postmenopausal women

Symptoms and Signs

• Diagnosis depends primarily on the history

• Angina most commonly arises during activity and is relieved by rest

• Patient often prefers to remain upright rather than lie down

• Rather than "pain," patient may describe tightness, squeezing, burning, pressure, choking, aching, bursting, "gas," indigestion, or ill-characterized discomfort

• Discomfort behind or slightly to the left of the mid-sternum

• May radiate to

  • Left shoulder and upper arm

  • Medial aspect of arm, elbow, forearm, wrist, and fourth and fifth fingers

  • Right shoulder or arm

  • Lower jaw

  • Nape of neck

  • Interscapular area

• May be associated with systemic symptoms, such as nausea, diaphoresis, dyspnea, palpitations

• Diagnosis strongly supported if sublingual nitroglycerin aborts or attenuates length of attack

• Physical examination during an attack often reveals a significant elevation in systolic and diastolic blood pressure

• Hypotension is a more ominous sign

• Gallop rhythm and an apical systolic murmur due to transient mitral regurgitation from papillary muscle dysfunction are present during pain only

• Supraventricular or ventricular arrhythmias may be present, either as the precipitating factor or as a result of ischemia

Differential Diagnosis

• Cardiovascular

  • Myocardial infarction (MI)

  • Pericarditis

  • Aortic stenosis

  • Aortic dissection

  • Cardiomyopathy

  • Myocarditis

  • Mitral valve prolapse

  • Pulmonary hypertension

  • Hypertrophic cardiomyopathy

  • Carditis in acute rheumatic fever

  • Aortic regurgitation

  • Right ventricular hypertrophy

• Pulmonary

  • Pneumonia

  • Pleuritis

  • Bronchitis

  • Pneumothorax

  • Tumor

  • Mediastinitis

• Gastrointestinal

  • Esophageal rupture

  • Gastroesophageal reflux disease

  • Esophageal spasm

  • Mallory-Weiss tear

  • Peptic ulcer disease

  • Biliary disease

  • Pancreatitis

  • Functional gastrointestinal pain

• Musculoskeletal

  • Cervical or thoracic disk disease or arthritis

  • Shoulder arthritis

  • Costochondritis or Tietze syndrome

  • Subacromial bursitis

• Other

  • Anxiety

  • Herpes zoster

  • Breast disorders

  • Chest wall tumors

  • Thoracic outlet syndrome

Laboratory Tests

• Troponin and creatine kinase (CK-MB) to evaluate for acute coronary syndrome

• Obtain a fasting lipid profile

• Rule out diabetes mellitus and anemia

Imaging Studies

• Indications for myocardial stress imaging (scintigraphy, echocardiography, MRI)

  • Patients are physically unable to exercise

  • ECG is difficult to interpret (eg, LBBB)

  • Results of exercise testing contradict the clinical impression

  • Need to localize the ischemia more precisely

  • Assess the completeness of revascularization

  • Prognostic indicator

• Scintigraphy

  • Can provide more information about the presence, location, and extent of coronary artery disease than exercise testing

  • Performed both at rest and during stress (exercise or pharmacologic stimulation)

• Echocardiography

  • Performed during supine exercise or immediately following upright exercise

  • May demonstrate exercise-induced segmental wall motion abnormalities

  • While exercise is the preferred stress because of other information derived, pharmacologic stress with high-dose dobutamine (20–40 mcg/kg/min) can be used as an alternative

• Cardiac MRI

  • Using gadolinium, provides high-resolution images of the heart and great vessels without radiation exposure or use of iodinated contrast media

  • Provides excellent assessment of pericardial disease, neoplastic disease of the heart, myocardial thickness, chamber size, and many congenital heart defects

  • Excellent noninvasive test for nonemergently evaluating dissection of the aorta

  • Gadolinium has been associated with necrotizing systemic fibrosis, a rare but fatal complication in patients with severe kidney disease

Diagnostic Procedures

• Obtain an ECG in all patients and, if possible, compare ECGs when pain is and is not present

• During anginal episodes as well as asymptomatic ischemia, the ECG may reveal horizontal or downsloping ST-segment depression, or T wave flattening or inversion that reverses after ischemia disappears or, less commonly, ST-segment elevation

• Exercise testing (treadmill or bicycle) is the least expensive and most useful noninvasive procedure to

  • Confirm the diagnosis of angina

  • Determine the severity of limitation of activity

  • Assess prognosis

  • Evaluate responses to therapy

• Coronary arteriography is the definitive diagnostic procedure

• Arteriography has a mortality rate of ~0.1% and morbidity of ~1–5%, and it is expensive

• Left ventricular angiography performed at the same time assesses left ventricular function and mitral regurgitation

• Multislice CT angiography

  • May be useful in evaluating patients with low likelihood of significant CAD to rule out disease

  • May also be useful for evaluating chest pain and suspected acute coronary syndrome

  • Is associated with lower 5-year mortality compared to standard care in patients with stable chest pain in one study

  • Radiation exposure is lower than radionuclide SPECT imaging

• CT angiography with noninvasive functional assessment of coronary stenosis (fractional flow reserve [CT-FFR])

  • Has also been evaluated in patients with low-intermediate likelihood of CAD

  • Has been shown to reduce the number of patients without coronary disease requiring invasive angiography

  • Is approved for clinical use and is being used in the United States and Europe

Medications

• Nitroglycerin, 0.3–0.6 mg sublingual or 0.4–0.8 mg by spray, with onset of symptoms or prophylactically 5 min before activity

• Long-acting nitrates (isosorbide dinitrate or mononitrate) for symptom management: avoid use for 8–10 h each day to avoid tolerance

• Beta-blockers reduce myocardial oxygen demand and benefit mortality

• Aspirin, 81–325 mg/day orally, reduces the risk of coronary thromboembolism and benefits mortality

• Ranolazine, 500 mg twice daily orally, for chronic angina

  • Contraindicated in significant liver and kidney disease

  • Can cause QT prolongation

  • Approved in Europe

• P2Y₁₂ inhibitors

  • Clopidogrel (75 mg/day orally) reduces the risk of coronary thromboembolism and benefits mortality in aspirin-intolerant patients

  • Ticagrelor

    • Has been shown to reduce cardiovascular events in patients with acute coronary syndromes

    • Long-term treatment in addition to aspirin reduced cardiovascular events compared to aspirin alone in patients with prior MI

    • Did not reduce cardiovascular events in patients with peripheral artery disease when compared to clopidogrel

• Dual antiplatelet therapy

  • Prolonged used of dual antiplatelet therapy with aspirin and clopidogrel may be beneficial in patients with drug-eluting stents

  • Guidelines recommend dual antiplatelet therapy (aspirin + P2Y12 therapy) in patients

    • Who had an MI within 1 year

    • Who underwent stenting within 6 months

    • Who received prolonged therapy (> 1 year) and are at high ischemic risk (multi-vessel coronary disease or polyvascular disease beds involved) and low bleeding risk

  • Rivaroxaban (2.5 mg twice daily)

    • Reduces cardiovascular events when combined with low-dose aspirin in patients with known coronary artery disease or peripheral artery disease

    • Approved by the FDA; provides another option for patients

• Ivabradine

  • Selectively blocks the I_f current and specifically lowers heart rate

  • Has been shown to reduce angina in patients with chronic stable angina

  • The SIGNIFY trial found no overall difference in clinical outcomes when patients with stable angina without heart failure were given ivabradine to reduce heart rate, and ivabradine may be harmful for patients with significant angina with regard to outcomes of cardiovascular death and MI

• Vorapaxar

  • Inhibits the protease-activated receptor-1

  • Has been shown to reduce cardiovascular events for patients with stable atherosclerosis with a history of MI or peripheral artery disease

  • Contraindicated for patients with history of stroke or transient ischemic attack due to increased risk of intracranial hemorrhage

• Calcium channel blockers are generally not indicated except to treat coronary vasospasm

Surgery

• Revascularization (coronary bypass grafting or angioplasty) is indicated when

  • Symptoms are unacceptable despite maximal medical therapy

  • There is > 50% stenosis of the left main coronary artery with or without symptoms

  • Triple-vessel disease coexists with either an ejection fraction < 50% or a prior MI

  • Unstable angina is present

  • Angina or severe ischemia persists on noninvasive testing after MI

• Coronary bypass grafting is generally reserved for left main and triple-vessel disease

Therapeutic Procedures

• Angioplasty or stenting performed during angiography

  • The procedure of choice for single-vessel disease in the setting of refractory symptoms

  • Superior to medical therapy for symptom relief, but not in preventing infarction or death

  • A high rate (~40%) of restenosis may be reduced with newer stents

Prevention

• Smoking cessation

• Beta-blockers, nitrates, and aspirin

• Vigorous treatment of hyperlipidemia (goal LDL < 100 mg/dL, HDL > 45 mg/dL)

• Tight control of diabetes mellitus

• Goal blood pressure (< 140/90 mm Hg)

• Avoiding aggravating factors: strenuous activity, cold temperatures, strong emotion

When to Refer

• All patients with new or worsening symptoms believed to represent progressive angina or a positive stress test for myocardial ischemia with continued angina despite medical therapy (or both) should be referred to a cardiologist

When to Admit

• Patients with elevated cardiac biomarkers, ischemic ECG findings, or hemodynamic instability

• Patients with new or worsened symptoms possibly thought to be ischemic but who lack high risk features can be observed with serial ECGs and biomarkers, and discharged if stress testing shows low risk findings