Chapter 20: Acute Coronary Syndrome

Acute coronary syndrome (ACS) encompasses unstable angina, ST elevation myocardial infarction (STEMI), and non-ST-elevation myocardial infarction (NSTEMI). It is the symptomatic cardiac end product of cardiovascular disease (CVD) resulting in reversible or irreversible cardiac injury, and even death.

The diagnosis of ACS requires two of the following: ischemic symptoms, diagnostic electrocardiogram (ECG) changes, or elevated serum marker of cardiac injury.

A. Symptoms

By themselves, signs and symptoms are not sufficient to diagnose or rule out ACS, but they start the investigatory cascade. Having known risk factors for coronary artery disease (CAD) (Table 20-1) or prior ACS increases the likelihood of ACS. Up to one-third of people with CAD progress to ACS with chest pain. While chest pain is the predominant symptom of ACS, it is not always present. Symptoms include the following:

• Chest pain

  • Classic: substernal pain that occurs with exertion and alleviates with rest (In a person with a history of CAD, this called “typical” or “stable” angina)

  • Dull, heavy pressure in or on the chest

  • Sensation of a heavy object on the chest

  • Initiated by stress, exercise, large meals, sex, or any activity that increases the body’s demand on the heart for blood

  • Lasting >20 minutes

  • Radiating to the back, neck, jaw, left arm or shoulder

  • Accompanied by feeling clammy or sweaty

  • Associated with sensation of dry mouth (women)

  • Not affected by inspiration

  • Not reproducible with chest palpation

• Right-sided chest pain, occasionally

  • More common in African-American patients

• Pain high in the abdomen or chest, nausea, extreme fatigue after exercise, back pain, and edema can occur in anyone, but are more common in women

• Extreme fatigue or edema after exercise

• Shortness of breath

  • This can be the only sign in the elderly

  • More common in African-American than white patients

  • More common in women than men

• Levine’s sign—chest discomfort described as a clenched fist over the sternum (the patient will clench his/her fist and rest it on or hover it over his/her sternum)

• Angor anami—great fear of impending doom/death

• Nausea, lightheadedness, or dizziness

• Less commonly

  • Mild, burning chest discomfort

  • Sharp chest pain

  • Pain that radiates to the right arm or back

  • A sudden urge to defecate in conjunction with chest pain

Chest pain that is present for days, is pleuritic, is positional, or radiates to the lower extremities or above the mandible is less likely to be cardiac in origin.

B. Physical Findings

Examination findings that increase the probability that symptoms are from ACS include hypotension, diaphoresis, and systolic heart failure indicated by a new S₃ gallop, new or worsening mitral valve regurgitation, pulmonary edema, and jugular venous distention.

Chest pain reproducible with palpation is significantly less likely to be ACS.

C. Diagnostic Testing

Anyone suspected of having ACS should be evaluated with a 12-lead electrocardiogram (ECG) and serum cardiac biomarkers (eg, troponin, CPK-MB).

Notable ECG findings are as follows:

• ST-T segment (>1–mm elevation or depression) and T-wave (inversion) changes suggest ischemia.

• Q wave suggests accomplished infarction.

• ST elevation is absent in unstable angina and NSTEMI.

• New bundle branch block or sustained ventricular tachycardia indicates a higher risk of progression to infarction.

Accurate ECG interpretation is essential for diagnosis, risk stratification, and guiding the treatment plan. Many findings are non-specific, and the pre-existing presence of bundle branch block (BBB), interventricular conduction delay (IVCD), or Wolff-Parkinson-White syndrome reduce the diagnostic reliability of an ECG in patients with chest pain. If there is a recent ECG for comparison the presence of a new BBB or IVCD raises the suspicion of ACS.

A normal ECG does not exclude ACS. Up to 25–50% of people with angina or silent ischemia have a normal ECG; 10% of ACS is subsequently diagnosed with an MI after an initial normal ECG.

Cardiac biomarkers are blood tests that indicate myocardial damage. Troponins T and I are preferred because of their high sensitivity and specificity for myocardial injury. Troponin I is most preferred because troponin T is more likely to be elevated by renal disease, polymyositis, or dermatomyositis. Newer highly sensitive troponin I assays have a 97–99%, negative predictive value of depending on the chosen cutoff value, as early as 3 hours after the onset of symptoms. However, the specificity is lower, resulting in a tradeoff–fewer false negatives afford earlier diagnosis at the cost of more false positives. The potential impact of this will be discussed in the treatment section of this chapter. Troponin remains elevated for 7–10 days, and can therefore help identify prior recent infarctions.

When initial ECG and cardiac markers are normal, they should be repeated within 6–12 hours of symptom onset. If they are normal a second time, exercise or pharmacological cardiac stress testing should be done to evaluate for inducible ischemia. Exercise stress testing (EST) is preferred, but stress testing with chemicals (dobutamine, dipyridamole, or adenosine) can be used to simulate the cardiac effects of exercise in those unable to exercise enough to produce a test adequate for interpretation.

Exercise stress testing is the main test for evaluating those with suspected angina or heart disease (Table 20-2). Interpretation of the test is based on the occurrence of signs of stress-induced impairment of myocardial contraction, including ECG changes (Table 20-3) and/or symptoms and signs of angina. The false-positive rate is 10%.

Adding radionuclide myocardial perfusion imaging (Table 20-4) to EST can improve sensitivity, specificity, and accuracy, especially in patients with a nondiagnostic exercise test or limited exercise ability. Acute rest myocardial perfusion imaging is very similar, but is performed during or shortly after resolution of angina symptoms that were not induced by a stress test. Radionucleatide EST can be advantageous in women because EST is less accurate in women compared to men.

Chest radiography (CXR) is used to assess for non-ACS causes of chest pain (eg, aortic dissection, pneumothorax, pulmonary embolus, pneumonia, rib fracture).

Echocardiography can be used to determine left ventricle ejection fraction, assess cardiac valve function, and detect regional wall motion abnormalities that correspond to areas of myocardial damage. Its high sensitivity and low specificity make it most useful to exclude ACS if the study is normal. It can also be used as an adjunct to stress testing. Since stress-induced impairment of myocardial contraction precedes ECG changes and angina, stress echocardiography, done and interpreted by experienced clinicians, can be superior to EST.

Cardiac magnetic resonance imaging does not yet have a clinical role because its sensitivity and specificity for detecting significant CAD plaque do not eclipse angiography, the gold standard.

Electron-beam computed tomography (EBCT) currently lacks utility since a positive test does not correlate well to an ACS episode. The future role of EBCT may change as more studies are done with higher resolution CT machines.

Coronary angiography is the gold standard. Main indications are in Table 20-5. Risks include death (1 in 1400), stroke (1 in 1000), coronary artery dissection (1 in 1000), arterial access complications (1 in 500), and minor risks such as arrhythmia; 10–30% of angiography studies are normal.

Cardiovascular disease (CVD) includes all diseases of the heart and vascular (eg, stroke and hypertension). CAD, synonymous with coronary heart disease (CHD), affects the coronary arteries by diminishing their ability to be a conduit for carrying oxygenated blood to the heart.

A. Atherosclerosis Progression

Atherosclerotic disease is the thickening and hardening (loss of elasticity) of the arterial wall due to the accumulations of lipids, macrophages, T lymphocytes, smooth-muscle cells, extracellular matrix, calcium, and necrotic debris. Figures 20-1,20-2, and 20-3 grossly depict the multifactorial and complex depository, inflammatory, and reactive processes that collaborate to occlude coronary arteries.

B. Genetic Predisposition

Traditional risk factors for CAD include high LDL cholesterol, low HDL cholesterol, hypertension, family history of CAD, diabetes, smoking, menopause for women, and age >45 for men. Some inherited risk factors (eg, dyslipidemia and propensity for diabetes mellitus) are modifiable; others (eg, age and sex) are not. Genes affect the development and progression of disease and its response to risk factor modification and lifestyle decisions; nature (genetics) meets nurture (environment) and they responsively interrelate (Table 20-6). Obesity is an excellent example of the dynamics of the interplay between genetics and environment.

The cascade of events of CHD that lead to ACS can be interrupted, delayed, or treated. Primary prevention tries to prevent disease before it develops, namely, prevent or delay development of risk factors (eg, prevent the onset of smoking, obesity, diabetes, or hypertension). Secondary prevention attempts to prevent disease progression by identifying and treating risk factors or preclinical, asymptomatic disease (eg, treat hypertension or nicotine addiction before the occurrence of ACS). Tertiary prevention is treatment of established disease to restore and maintain highest function, minimize negative disease effects, and prevent complications, that is, help recover from and prevent recurrence of ACS (eg, treatment of hypertension and lowering LDL target from 100 mg/dL to 70 mg/dL after the occurrence of ACS).

Primary prevention of ACS should begin in childhood by preventing tobacco use, eating a diet rich in fruits and vegetable and low in saturated fats, exercising regularly for 20–30 minutes 5 times a week, and maintaining a BMI of 18–28 kg/m². Compared to waiting to initiate secondary and tertiary strategies, these primary prevention strategies yield a larger impact on decreasing lifetime risk of death from ACS and years of productive life lost to ACS.

Secondary and tertiary preventions involve increasingly aggressive management of those who have known risk factors for or have experienced ACS (Figure 20-4 and Table 20-7). Although the association between cholesterol and ACS death is weaker in those aged >65 years, HMG-CoA reductase inhibitor drugs (statins) still positively impact morbidity and mortality in this demographic. This may be due to their effects that go beyond their lipid lowering: pleiotropic effects such as anti-inflammation and endothelial stabilizing.

Some once touted therapies have been found to be ineffective. Because of a lack of effect and potential harm, estrogen ± progestin hormone replacement therapy should not be used as primary, secondary, or tertiary prevention of CAD. Antibiotics and the antioxidants folate, vitamin C, and vitamin E do not improve ACS morbidity and mortality.

Cardiac rehabilitation, an example of tertiary prevention, is a multidisciplinary attempt to prevent future ACS by focusing on three areas: exercise, risk factor modification, and psychosocial intervention. Optimal medical management is part of this process. Patient adherence to the plan is integral to long-term success.

Exercise-based rehabilitation programs reduce both all-cause and cardiac mortality in patients with a history of myocardial infarction, surgical intervention [percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG)], or stable CAD.

Risk factor modification addresses the content of Figure 20-4 and Table 20-7; involves dietician-guided nutritional training; and emphasizes smoking cessation via counseling, drug therapy (bupropion, varenicline), nicotine replacement, and formal cessation programs.

Psychosocial intervention emphasizes the identification and management of the psychological and social effects that can follow ACS. These effects can include depression, anxiety, family issues, and job-related problems. Depression has been linked to worse mortality in patients with CHD. Psychosocial intervention alone does not affect total or cardiac mortality, but does decrease depression and anxiety, which may impact quality of life.

These are listed as follows:

• Anemia

• Aortic aneurysm

• Aortic dissection

• Cardiac tamponade

• Cardiac valve rupture

• Cardiomyopathy

• Cholecystitis

• Costochondritis

• Coronary artery anomaly or aneurysm

• Diaphragramatic irritation/inflammation due to

  • Hepatitis

  • Infection

  • Mass effect from nearby cancer

  • Pancreatitis

  • Pulmonary edema/effusion

• Drug use (eg, cocaine)

• Duodenal ulcer

• Esophageal spasm

• Esophagitis

• Gastritis

• Generalized anxiety disorder (GAD)

• Gastroesophageal reflux disease (GERD)

• Hiatal hernia

• High-altitude exposure

• Hyperthyroidism

• Panic attack

• Peptic ulcer disease

• Pericardial effusion

• Pericarditis

• Pleurisy/pleuritis

• Pneumothorax

• Prinzmetal’s angina (coronary vasospasm)—more common in women

• Pulmonary embolus

• Pulmonary hypertension

• Radiculopathy

• Shoulder arthropathy

• Stress reactional anxiety

• Supraventricular tachycardia

• Vasculitis

There are four major complications: (1) death, (2) myocardial infarction (MI), (3) hospitalization, and (4) cardiac disability—lifestyle and activity options are diminished because the heart is unable to supply the oxygenated blood that the body needs to fulfill its demand because the coronary arteries are unable to supply the heart muscle.

There is one important formula to keep in mind for management of ACS:

ACS causes myocardial infarction (MI) in three ways:

1. Atheromatous plaque buildup increases till the artery is totally occluded.

2. An atheromatous plaque ruptures or tears, leading to occlusions via inflammatory response and thrombus formation as platelets adhere to the site to seal off the plaque.

3. Superimposition of thrombus on a disrupted atherosclerotic plaque.

The goal of treatment is to save cardiac muscle by reducing myocardial oxygen demand and/or increasing oxygen supply.

All patients with ACS should be hospitalized, be medically stabilized, and receive further cardiac evaluation to determine STEMI versus NSTEMI versus unstable angina and then treatment appropriate to the diagnosis. Immediate PCI can be beneficial for STEMI, but can be safely delayed in low-risk NSTEMI. All ACS patients should receive medical management, which begins with the mnemonic HOBANACS:

Heparin (low-molecular-weight heparin→fewer MIs and deaths)

• Oxygen

• Beta-blocker (β-blocker; if hemodynamically stable: metoprolol, timolol, propranolol, or carvedilol if decreased ejection fraction)

• Aspirin (initially 160–325 mg each day then 70–162 mg daily indefinitely)

• Nitroglycerin (for pain; stop if hypotension occurs)

• ACE inhibitor (angiotensin-converting enzyme inhibitor; within the first 24 hours if anterior-location infarct, heart failure, or ejection fraction of ≤40%, unless contraindicated)

• Clopidogrel (up to 1 year; not within 5 days of CABG)

• Statins (HMG-CoA-reductase inhibitors; goal LDL <70 mg/dL)

Morphine may be added for pain and anxiety relief. It also provides some afterload reduction.

Anticoagulation with heparin starts with low-molecular-weight heparin if PCI is not planned. Unfractionated heparin should be used if creatinine clearance <60 mL/minute or if early PCI or CABG is planned within 24 hours. Fondaparinux is as effective as enoxaparin with less major bleeding and lower long-term mortality.

Beta-blockers decrease the workload on the heart by slowing it down and decreasing blood pressure. The goal should be <130/85 mmHg or < 130/80 mmHg if diabetes or chronic kidney disease is present; optimal blood pressure may be 115/75 mmHg.

Aspirin (ASA) should be continued indefinitely. Once ACS is stabilized, a dose of 81 mg per day should suffice. If ASA is not tolerated, clopidogrel should be used. If there is a history of gastrointestinal bleeding and either ASA or clopidogrel is used, drugs to decrease the risk of recurrent gastrointestinal bleeding (eg, proton-pump inhibitors) should be given.

Clopidogrel requires a loading dose (300–600 mg) followed by the daily maintenance dose (75 mg). If there is no plan for PCI, it should be added to aspirin and anticoagulant therapy as soon as possible after admission. If PCI is likely, it can be added before the procedure. Duration of treatment should be for at least 3 months and ideally up to 1 year. Ticagrelor (180 mg load then 90 mg twice daily) compared to clopidogrel resulted in lower all-cause mortality, vascular mortality, and MI rate without increase in major bleeding or stroke. Prasugrel (5–10 mg daily) compared to clopidogrel has not shown lower risk of death from cardiovascular causes, myocardial infarction, or stroke, and bleeding risks are similar.

Platelet glycoprotein IIB/IIIA (GP IIB/IIIA) receptor inhibitors should be used judiciously if there is no plan for revascularization: 100 STEMIs need to be treated to prevent one MI or death, but for every one prevention there is one major bleeding complication. Specifically, abciximab should be used only if PCI is planned.

Reperfusion–PCI, CABG, medications can also be used. If cardiac tissue is to survive, blood flow must be restored. STEMI (active infarctions) require medical thrombolysis or emergent angioplasty to achieve this. Primary PCI is the recommended method of reperfusion. If PCI or CABG cannot be initiated within 120 minutes, then thrombolytic, fibrinolytic agents should be started within 30–60 minutes. When medical therapy is used because PCI/CABG cannot be initiated within 120 minutes, if blood flow is still not restored, then proceed to PCI/CABG as soon as possible without a “cooling off” period A cooling-off period (ie, delaying PCI or CABG because of failed medical thrombolysis, increases mortality without decreasing bleeding complications).

While there is a modest decrease in recurrent ischemia, early PCI within 24 hours of symptom onset for lower-risk NSTEMI patients does not decrease mortality compared to late PCI within 36 hours. Higher-risk patients (ST >1-mm depression, T wave inversion, impaired renal function, hemodynamically unstable, TIMI1 score > 4, GRACE2 >140, presence of heart failure) with NSTEMI benefit from early PCI within 24 hours. There is no difference in NSTEMI mortality between PCI in 70 minutes compared to 21 hours in higher-risk patients (TIMI score is >4).

The 2-year risk of death or recurrent MI is the same for PCI and CABG, but approximately 5% with a CABG get less angina.

Post-MI care should center around tertiary care (see cardiac rehabilitation, illustrated in Figure 20-4, and Table 20-7). Optimal blood pressure is closer to 115/75 mmHg, since in 40–70-year-olds each increment of 20 mmHg in systolic BP or 10 mmHg in diastolic BP doubles the risk of CVD across the entire BP range from 115/75 mmHg to 185/115 mmHg.

Cyclooxygenase-2 (COX2) nonsteroidal anti-inflammatory drugs and naproxen should be avoided because they increase risk for ACS.

For some individuals, using warfarin (goal INR 2.0–3.0) together with aspirin or warfarin alone (goal INR 3.0–4.0) results in a better all-cause mortality than taking aspirin alone. It reduces the risk of myocardial infarction and stroke but increases the risk of major bleeding.

Cultural issues can affect the diagnosis, treatment, and outcome of ACS. Some clinical symptoms are more common in certain patient populations (see prior symptoms list). Overall, atypical symptoms are more prevalent in women and elderly patients. Symptoms may include jaw and neck pain, dyspnea, fatigue, dry mouth, palpitations, indigestion, cough, and nausea and emesis. Maybe because atypical symptoms occur more frequently in women and older adults, they tend to experience delaying diagnosis, less aggressive treatment, and increased rates of in-hospital mortality.

Other notable differences exist between patient populations that relate to diagnosis and treatment of cardiac disease. Both men and women with ACS respond to early invasive treatment. Women tend to have a more severe first ACS, are less likely to receive thrombolysis, and are at greater risk for death and hospital readmission at 6 months. Patients with symptoms of acute MI are less often hospitalized if they are nonwhite or have a normal or nondiagnostic ECG. Patients experiencing ACS who are women <55 years of age, are nonwhite, have shortness of breath as their chief complaint, or have a normal or indeterminate ECG and are less often hospitalized, thus increasing their morality. After ACS, women are more likely than men to experience depression and hence its ramifications.

Patients are more likely to adhere to treatment plans that they can afford. This should be taken into account when deciding which medication to prescribe and which diets and exercise plans to recommend. Emphasize free and low-cost exercise options; remember that some diet approaches are less expensive than others.

An estimated 60% of myocardial infarction deaths occur within the first hour of symptom onset. Prognosis following a survived MI without subsequent intervention carries a mortality rate of 10% the first year and 5% each additional year. Sudden death, more common in patients with a lower ejection fraction, following ACS occurs in 1.4% of patients during the first month, and decreases to 0.14% per month after 2 years.

When either troponin T or I level is normal at 2, 4, and 6 hours after the onset of chest pain in patients with a normal ECG, the 30-day risk of cardiac death and nonfatal acute MI is nearly zero.

Normal troponin T levels at 10–12 hours after symptom onset in patients with chest pain and a normal ECG indicate a low risk of adverse events for the next 12 months. Even slight elevations in cardiac troponin levels in patients with unstable angina and NSTEMI help identify high-risk patients who may benefit the most from early invasive treatment.

Website-accessible scoring systems can help risk-stratify patients with chest pain and help determine prognosis given a range of different circumstances by analyzing individual patient characteristics and test results. Prognostic tools are valuable when educating patients about possible outcomes, and when discussing and deciding on treatment options.

For Information on ACS & CVD

For Informaion on Other Cardiac Disorders