Key Points
- It is estimated that 1 in 3 adults in the United States (about 81 million) has some form of cardiovascular disease, including >17 million with ischemic heart disease and nearly 10 million with angina pectoris.
- Among persons 60-79 years of age, approximately 25% of men and 16% of women have ischemic heart disease, and these figures rise to 37% and 23% among men and women >80 years of age, respectively.
- Ischemic Heart Disease (IHD) is the number one cause of death in both men and women. It was responsible for nearly 380,000 deaths in the United States during 2010, with an age-adjusted mortality rate of 113 per 100,000 population.
- The total estimated cost for heart disease in the US in 2010 was $316 billion.
- Angina pectoris is the initial manifestation of IHD in approximately 50% of patients.
- Choices about diagnostic and therapeutic options should be made through a process of shared decision making involving the patient and provider, with the provider explaining information about risks, benefits, and costs to the patient. (I-C)
Diagnosis
Table 1. Clinical Classification of Chest Pain
| Typical angina (definite) | 1) Substernal chest discomfort with a characteristic quality and duration that is: 2) provoked by exertion or emotional stress and 3) relieved by rest or nitroglycerin |
| Atypical angina (probable) | Meets 2 of the above characteristics |
| Noncardiac chest pain | Meets 1 or none of the typical anginal characteristics |
Figure 1. Spectrum of Ischemic Heart Disease (IHD)
Table 2. Three Principal Presentations of Unstable Angina (UA)
TIMI Risk Score for UA/NSTEMI Calculator
| Rest angina | Angina occurring at rest and usually prolonged >20 min, occurring within 1 wk of presentation |
| New-onset angina | Angina of at least CCS Class III severity with onset within 2 mo of initial presentation |
| Increasing angina | Previously diagnosed angina that is distinctly more frequent, longer in duration, or lower in threshold (ie, increased by ≥1 CCS class within 2 mo of initial presentation to ≥CCS Class III severity) |
Class I – Angina only during strenuous or prolonged physical activity
Class II – Slight limitation, with angina only during vigorous physical activity
Class III – Symptoms with everyday living activities, ie, moderate limitation
Class IV – Inability to perform any activity without angina or angina at rest, ie, severe limitation
Table 3. Alternative Diagnoses to Angina for Patients with Chest Pain
| Nonischemic Cardiovascular | Pulmonary | Gastrointestinal | Chest Wall | Psychiatric |
|---|---|---|---|---|
| Aortic dissection | Pulmonary embolism | Esophageal Esophagitis Spasm Reflux | Costochondritis Fibrositis Rib fracture Sternoclavicular arthritis Herpes zoster (before the rash) | Anxiety disorders Hyperventilation Panic disorder Primary anxiety |
| Pericarditis | Pneumothorax Pneumonia Pleuritis | Biliary Colic Choledocholithiasis Cholangitis Peptic ulcer Pancreatitis | Affective disorders (ie, depression) Somatiform disorders Thought disorders (ie, fixed delusions) |
Table 4. Pretest Likelihood of Coronary Artery Disease (CAD) in Symptomatic Patients According to Age and Sexa
| Age, y | Nonanginal Chest Pain | Atypical Angina | Typical Angina | |||
|---|---|---|---|---|---|---|
| Men | Women | Men | Women | Men | Women | |
| 30-39 | 4 | 2 | 34 | 12 | 76 | 26 |
| 40-49 | 13 | 3 | 51 | 22 | 87 | 55 |
| 50-59 | 20 | 7 | 65 | 31 | 93 | 73 |
| 60-69 | 27 | 14 | 72 | 51 | 94 | 86 |
Adapted from Forrester and Diamond. N Engl J Med. 1979;300:1350-8.
Table 5. Comparing Pretest Likelihood of CAD in Low-Risk Symptomatic Patients With High-Risk Symptomatic Patients
| Age, y | Nonanginal Chest Pain | Atypical Angina | Typical Angina | |||
|---|---|---|---|---|---|---|
| Men | Women | Men | Women | Men | Women | |
| 35 | 3-35 | 1-19 | 8-59 | 2-39 | 30-88 | 10-78 |
| 45 | 9-47 | 2-22 | 21-70 | 5-43 | 51-92 | 20-79 |
| 55 | 23-59 | 4-21 | 45-79 | 10-47 | 80-95 | 38-82 |
| 65 | 49-69 | 9-29 | 71-86 | 20-51 | 93-97 | 56-84 |
Table 6. Medical Conditions Provoking or Exacerbating Ischemia
| Increased Oxygen Demand | Decreased Oxygen Supply |
|---|---|
| Noncardiac | Noncardiac |
| Hyperthermia | Anemia |
| Hyperthyroidism | Hypoxemia |
| Sympathomimetic toxicity (ie, cocaine use) | Pneumonia |
| Hypertension | Asthma |
| Anxiety | Chronic obstructive pulmonary disease |
| Arteriovenous fistulae | Pulmonary hypertension |
| Interstitial pulmonary fibrosis | |
| Obstructive sleep apnea | |
| Sickle cell disease | |
| Sympathomimetic toxicity (ie, cocaine use, pheochromocytoma) | |
| Hyperviscosity | |
| Polycythemia | |
| Leukemia | |
| Thrombocytosis | |
| Hypergammaglobulinemia | |
| Cardiac | Cardiac |
| Hypertrophic cardiomyopathy | Aortic stenosis |
| Aortic stenosis | Hypertrophic cardiomyopathy |
| Dilated cardiomyopathy | Significant coronary obstruction |
| Tachycardia | Microvascular disease |
| Ventricular | Congenital cardiac anomalies |
| Supraventricular | Shunts |
| Fistulae |
Figure 2. Diagnosis of Patients with Suspected Ischemic Heart Disease
Figure 3. Risk Assessment of Patients with Stable Ischemic Heart Disease (SIHD)
Figure 4. Guideline-Directed Medical Therapy for Patients with SIHD
Figure 5. Revascularization to Improve Survival of Patients with SIHD
Clinical Evaluation in the Initial Diagnosis of SIHD in Patients With Chest Pain
- Patients with chest pain should receive a thorough history and physical examination to assess the probability of IHD before additional testing. (I-C)
- Patients who present with acute angina should be categorized as stable or unstable. Patients with unstable angina (UA) should be further categorized as being at high, moderate, or low risk. (I-C)
- A resting electrocardiogram (ECG) is recommended in patients without an obvious, noncardiac cause of chest pain (I-B)
Figure 6. Revascularization to Improve Symptoms of Patients with SIHD
Stress Testing and Advanced Imaging for Initial Diagnosis in Patients With Suspected SIHD Who Require Noninvasive Testing
Able to Exercise
- Standard exercise ECG testing is recommended for patients with an intermediate pretest probability of IHD who have an interpretable ECG and at least moderate physical functioning or no disabling comorbidity. (I-A)
- Exercise stress with nuclear myocardial perfusion imaging (MPI) or echocardiography is recommended for patients with an intermediate to high pretest probability of IHD who have an uninterpretable ECG and at least moderate physical functioning or no disabling comorbidity. (I-B)
- For patients with a low pretest probability of obstructive IHD who do require testing, standard exercise ECG testing can be useful, provided the patient has an interpretable ECG and at least moderate physical functioning or no disabling comorbidity. (IIa-C)
- Exercise stress with nuclear MPI or echocardiography is reasonable for patients with an intermediate to high pretest probability of obstructive IHD who have an interpretable ECG and at least moderate physical functioning or no disabling comorbidity. (IIa-B)
- Pharmacological stress with cardiac magnetic resonance (CMR) can be useful for patients with an intermediate to high pretest probability of obstructive IHD who have an uninterpretable ECG and at least moderate physical functioning or no disabling comorbidity. (IIa-B)
- Coronary/cardiac computed tomography angiography (CCTA) might be reasonable for patients with an intermediate pretest probability of IHD who have at least moderate physical functioning or no disabling comorbidity. (IIb-B)
- For patients with a low pretest probability of obstructive IHD who do require testing, standard exercise stress echocardiography might be reasonable, provided the patient has an interpretable ECG and at least moderate physical functioning or no disabling comorbidity. (IIb-C)
- Pharmacological stress with nuclear MPI, echocardiography, or cardiac magnetic resonance (CMR) is NOT recommended for patients who have an interpretable ECG and at least moderate physical functioning or no disabling comorbidity. (III-C: No Benefit)
- Exercise stress with nuclear MPI is NOT recommended as an initial test in low-risk patients who have an interpretable ECG and at least moderate physical functioning or no disabling comorbidity. (III-C: No Benefit)
Unable to Exercise
- Pharmacological stress with nuclear MPI or echocardiography is recommended for patients with an intermediate to high pretest probability of IHD who are incapable of at least moderate physical functioning or have disabling comorbidity. (I-B)
- Pharmacological stress echocardiography is reasonable for patients with a low pretest probability of IHD who require testing and are incapable of at least moderate physical functioning or have disabling comorbidity. (IIa-C)
- CCTA is reasonable for patients with a low to intermediate pretest probability of IHD who are incapable of at least moderate physical functioning or have disabling comorbidity. (IIa-B)
- Pharmacological stress CMR is reasonable for patients with an intermediate to high pretest probability of IHD who are incapable of at least moderate physical functioning or have disabling comorbidity. (IIa-B)
- Standard exercise ECG testing is NOT recommended for patients who have an uninterpretable ECG or are incapable of at least moderate physical functioning or have disabling comorbidity. (III-C: No Benefit)
- CCTA is reasonable for patients with an intermediate pretest probability of IHD who: (IIa-C)
- Have continued symptoms with prior normal test findings, or
- Have inconclusive results from prior exercise or pharmacological stress testing, or
- Are unable to undergo stress with nuclear MPI or echocardiography
- For patients with a low to intermediate pretest probability of obstructive IHD, noncontrast cardiac computed tomography (CT) to determine the coronary artery calcium (CAC) score may be considered. (IIb-C)
Table 7. Stress Testing and Advance Imaging for Initial Diagnosis in Patients with Suspected SIHD Who Require Noninvasive Testing
| Test | Exercise Status | ECG Interpretable | Pretest Probability of IHD | COR | LOE | ||||
|---|---|---|---|---|---|---|---|---|---|
| Able | Unable | Yes | No | Low | Intermediate | High | |||
| Patents able to exercise | |||||||||
| Exercise ECG | ✔ | ✔ | ✔ | I | A | ||||
| Exercise with nuclear MPI or Echo | ✔ | ✔ | ✔ | ✔ | I | B | |||
| Exercise ECG | ✔ | ✔ | ✔ | IIa | C | ||||
| Exercise with nuclear MPI or Echo | ✔ | ✔ | ✔ | ✔ | IIa | B | |||
| Pharmacological stress CMR | ✔ | ✔ | ✔ | ✔ | IIa | B | |||
| CCTA | ✔ | Any | ✔ | IIb | B | ||||
| Exercise Echo | ✔ | ✔ | ✔ | IIb | C | ||||
| Pharmacological stress with nuclear MPI, Echo or CMR | ✔ | ✔ | Any | III: No Benefit | C | ||||
| Exercise stress with nuclear MPI | ✔ | ✔ | ✔ | III: No Benefit | C | ||||
| Patients unable to exercise | |||||||||
| Pharmacological stress with nuclear MPI or Echo | ✔ | Any | ✔ | ✔ | I | B | |||
| Pharmacological stress Echo | ✔ | Any | ✔ | IIa | C | ||||
| CCTA | ✔ | Any | ✔ | ✔ | IIa | B | |||
| Pharmacological stress CMR | ✔ | Any | ✔ | ✔ | IIa | B | |||
| Exercise ECG | ✔ | ✔ | Any | III: No Benefit | C | ||||
| Other | |||||||||
| CCTA If patient has any of the following: a) Continued symptoms with prior normal test, or b) Inconclusive exercise or pharmacological stress, or c) Unable to undergo stress with MPI or Echo | Any | Any | ✔ | IIa | C | ||||
| CAC score | Any | Any | ✔ | IIb | C | ||||
Resting Imaging to Assess Cardiac Structure and Function
- Assessment of resting left ventricular (LV) systolic and diastolic function and evaluation for abnormalities of myocardium, heart valves, or pericardium are recommended with the use of Doppler echocardiography in patients with known or suspected IHD and a prior myocardial infarction (MI), pathological Q waves, symptoms or signs suggestive of heart failure, complex ventricular arrhythmias, or an undiagnosed heart murmur. (I-B)
- Assessment of cardiac structure and function with resting echocardiography may be considered in patients with hypertension or diabetes mellitus and an abnormal ECG. (IIb-C)
- Measurement of LV function with radionuclide imaging may be considered in patients with a prior MI or pathological Q waves, provided there is no need to evaluate symptoms or signs suggestive of heart failure, complex ventricular arrhythmias, or an undiagnosed heart murmur. (IIb-C)
- Echocardiography, radionuclide imaging, CMR, and cardiac CT are NOT recommended for routine assessment of LV function in patients with a normal ECG, no history of MI, no symptoms or signs suggestive of heart failure, and no complex ventricular arrhythmias. (III-C: No Benefit)
- Routine reassessment (<1 year) of LV function with technologies such as echocardiography radionuclide imaging, CMR, or cardiac CT is NOT recommended in patients with no change in clinical status and for whom no change in therapy is contemplated. (III-C: No Benefit)
Stress Testing and Advanced Imaging in Patients With Known SIHD Who Require Noninvasive Testing for Risk Assessment
Risk Assessment in Patients Able to Exercise
- Standard exercise ECG testing is recommended for risk assessment in patients with SIHD who are able to exercise to an adequate workload and have an interpretable ECG. (I-B)
- The addition of either nuclear MPI or echocardiography to standard exercise ECG testing is recommended for risk assessment in patients with SIHD who are able to exercise to an adequate workload but have an uninterpretable ECG not due to left bundle-branch block (LBBB) or ventricular pacing. (I-B)
- The addition of either nuclear MPI or echocardiography to standard exercise ECG testing is reasonable for risk assessment in patients with SIHD who are able to exercise to an adequate workload and have an interpretable ECG. (IIa-B)
- CMR with pharmacological stress is reasonable for risk assessment in patients with SIHD who are able to exercise to an adequate workload but have an uninterpretable ECG. (IIa-B)
- CCTA may be reasonable for risk assessment in patients with SIHD who are able to exercise to an adequate workload but have an uninterpretable ECG. (IIb-B)
- Pharmacological stress imaging (nuclear MPI, echocardiography, or CMR) or CCTA is NOT recommended for risk assessment in patients with SIHD who are able to exercise to an adequate workload and have an interpretable ECG. (III-C: No Benefit)
Risk Assessment In Patients Unable To Exercise
- Pharmacological stress with either nuclear MPI or echocardiography is recommended for risk assessment in patients with SIHD who are unable to exercise to an adequate workload regardless of interpretability of ECG. (I-B)
- Pharmacological stress CMR is reasonable for risk assessment in patients with SIHD who are unable to exercise to an adequate workload regardless of interpretability of ECG. (IIa-B)
- CCTA can be useful as a first-line test for risk assessment in patients with SIHD who are unable to exercise to an adequate workload regardless of interpretability of ECG. (IIa-C)
Risk Assessment Regardless Of Patients’ Ability To Exercise
- Pharmacological stress with either nuclear MPI or echocardiography is recommended for risk assessment in patients with SIHD who have LBBB on ECG, regardless of ability to exercise to an adequate workload. (I-B)
- Either exercise or pharmacological stress with imaging (nuclear MPI, echocardiography, or CMR) is recommended for risk assessment in patients with SIHD who are being considered for revascularization of known coronary stenosis of unclear physiological significance. (I-B)
- CCTA can be useful for risk assessment in patients with SIHD who have an indeterminate result from functional testing. (IIa-C)
- CCTA might be considered for risk assessment in patients with SIHD unable to undergo stress imaging or as an alternative to invasive coronary angiography when functional testing indicates a moderate-to high-risk result and angiographic coronary anatomy is unknown. (IIb-C)
- A request to perform either a) more than 1 stress imaging study or b) a stress imaging study and a CCTA at the same time is NOT recommended for risk assessment in patients with SIHD. (III-C: No Benefit)
Table 8. Using Stress Testing and Advanced Imaging for Patients With Known SIHD Who Require Noninvasive Testing for Risk Assessment
| Test | Exercise Status | ECG Interpretable | COR | LOE | Additional Considerations | ||
|---|---|---|---|---|---|---|---|
| Able | Unable | Yes | No | ||||
| Patents able to exercise* | |||||||
| Exercise ECG | ✔ | ✔ | I | B | |||
| Exercise with nuclear MPI or Echo | ✔ | ✔ | I | B | Abnormalitites other than LBBB or ventricular pacing | ||
| Exercise with nuclear MPI or Echo | ✔ | ✔ | IIa | B | |||
| Pharmacological stress CMR | ✔ | ✔ | IIa | B | |||
| CCTA | ✔ | ✔ | IIb | B | |||
| Pharmacological stress imaging (nuclear MPI, Echo, CMR) or CCTA | ✔ | ✔ | III: No Benefit | C | Without prior stress test | ||
| Patients unable to exercise | |||||||
| Pharmacological stress with nuclear MPI or Echo | ✔ | Any | I | B | |||
| Pharmacological CMR | ✔ | Any | IIa | B | |||
| CCTA | ✔ | Any | IIa | C | Without prior stress test | ||
| Regardless of patient's ability to exercise | |||||||
| Pharmacological stress with nuclear MPI or Echo | Any | ✔ | I | B | LBBB present | ||
| Exercise/pharmacological stress with nuclear MPI, Echo, or CMR | Any | Any | I | B | Known coronary stenosis of unclear physiological significance being considered for revascularization | ||
| CCTA | Any | Any | IIa | C | Indeterminate result from functional testing | ||
| CCTA | Any | Any | IIb | C | Unable to undergo stress imaging or as alternative to coronary catheterization when functional testing indicates moderate to high risk and angiographic coronary anatomy is unknown | ||
| Requests to perform multiple cardiac imaging or stress studies at the same time | Any | Any | III: No Benefit | C | |||
Coronary Angiography as an Initial Testing Strategy to Assess Risk
- Patients with SIHD who have survived sudden cardiac death or