Physical Address
304 North Cardinal St.
Dorchester Center, MA 02124
Ischemic heart disease
The prevalence of ischemic heart disease and atherosclerotic vascular disease in the United States increases significantly with age ( Fig. 5.1 ). By some estimates, 30% of patients who undergo surgery annually in the United States have ischemic heart disease. Angina pectoris, acute myocardial infarction (AMI), and sudden death are often the first manifestations of ischemic heart disease, and cardiac dysrhythmias are probably the major cause of sudden death in these patients. Genetic factors, a high- fat and energy-rich diet, smoking, and sedentary lifestyle are associated with the emergence of ischemic heart disease Additional risk factors include hypercholesterolemia, systemic hypertension, cigarette smoking, diabetes mellitus, obesity, and a family history of premature development of ischemic heart disease ( Table 5.1 ). Psychological factors such as type A personality and stress have also been implicated. Patients with ischemic heart disease can have chronic stable angina or an acute coronary syndrome (ACS) at presentation. The latter includes ST-segment elevation myocardial infarction (STEMI) and unstable angina/non–ST-segment elevation myocardial infarction (UA/NSTEMI).
Prevalence of coronary heart disease by age and gender in the United States (2013-2016).
(Data from National Center for Health Statistics and National Heart, Lung, and Blood Institute.)
TABLE 5.1
Risk Factors for Development of Ischemic Heart Disease
| Male gender Increasing age Hypercholesterolemia Hypertension Cigarette smoking Diabetes mellitus Obesity Sedentary lifestyle Genetic factors/family history |
Stable angina pectoris
The coronary artery circulation normally supplies sufficient blood flow to meet the demands of the myocardium in response to widely varying workloads. An imbalance between coronary blood flow (supply) and myocardial oxygen consumption (demand) can precipitate ischemia, which frequently manifests as chest pain (i.e., angina pectoris). Stable angina typically develops in the setting of partial occlusion or significant (>70%) chronic narrowing of a segment of coronary artery. When the imbalance becomes extreme, congestive heart failure, electrical instability with cardiac dysrhythmias, and MI may result. Angina pectoris reflects intracardiac release of adenosine, bradykinin, and other substances during ischemia. These substances stimulate cardiac nociceptive and mechanosensitive receptors whose afferent neurons converge with the upper five thoracic sympathetic ganglia and somatic nerve fibers in the spinal cord and ultimately produce thalamic and cortical stimulation that results in the typical chest pain of angina pectoris. These substances also slow atrioventricular conduction and decrease cardiac contractility, which improves the balance between myocardial oxygen supply and demand. Atherosclerosis is the most common cause of impaired coronary blood flow resulting in angina pectoris, but it may also occur in the absence of coronary obstruction as a result of myocardial hypertrophy, severe aortic stenosis, or aortic regurgitation. It may also occur with paroxysmal tachydysrhythmias, marked anemia, or hyperthyroidism. Syndrome X is a rare cause of angina, and in this situation the chest pain is thought to be due to microvascular dysfunction of the coronary circulation.
Diagnosis
Angina pectoris is typically described as retrosternal chest discomfort, pain, pressure, or heaviness that may radiate to any dermatome from C8 to T4. This chest discomfort often radiates to the neck, left shoulder, left arm, or jaw and occasionally to the back or down both arms (especially the ulnar surfaces of forearm and hand). Angina may also be perceived as epigastric discomfort resembling indigestion. Some patients describe angina as shortness of breath, mistaking a sense of chest constriction as dyspnea. The need to take a deep breath rather than breathe rapidly often identifies shortness of breath as an anginal equivalent. Angina pectoris usually lasts several minutes and is crescendo-decrescendo in nature. A sharp pain that lasts only a few seconds or a dull ache that lasts for hours is rarely caused by myocardial ischemia. Physical exertion, emotional tension, and cold weather may induce angina. Rest and/or nitroglycerin relieve it. Chronic stable angina refers to chest pain or discomfort that does not change appreciably in frequency or severity over 2 months or longer. Unstable angina, by contrast, is defined as angina at rest, angina of new onset, or an increase in the severity or frequency of previously stable angina without an increase in levels of cardiac biomarkers. Sharp retrosternal pain exacerbated by deep breathing, coughing, or change in body position suggests pericarditis. There are many causes of noncardiac chest pain ( Table 5.2 ). Noncardiac chest pain is often exacerbated by chest wall movement and is associated with tenderness over the involved area, which is often a costochondral junction. Esophageal spasm can produce severe substernal pressure that may be confused with angina pectoris and may also be relieved by administration of nitroglycerin.
TABLE 5.2
Common Causes of Acute Chest Pain
| System | Condition |
|---|---|
| Cardiac | Angina Rest or unstable angina Acute myocardial infarction Pericarditis |
| Vascular | Aortic dissection Pulmonary embolism Pulmonary hypertension |
| Pulmonary | Pleuritis and/or pneumonia Tracheobronchitis Spontaneous pneumothorax |
| Gastrointestinal | Esophageal reflux Peptic ulcer Gallbladder disease Pancreatitis |
| Musculoskeletal | Costochondritis Cervical disk disease Trauma or strain |
| Infectious | Herpes zoster |
| Psychological | Panic disorder |
Electrocardiography
The resting electrocardiogram (ECG) may be normal in patients with angina, or it may show nonspecific ST–T-wave changes or abnormalities related to an old MI. During myocardial ischemia, the standard 12-lead ECG demonstrates ST-segment depression (characteristic of subendocardial ischemia) that coincides in time with the anginal chest pain. This may be accompanied by transient symmetric T-wave inversion. Patients with chronically inverted T waves resulting from previous MI may show a return of the T waves to the normal upright position (i.e., pseudonormalization of the T wave) during myocardial ischemia. These ECG changes are seen in about half of patients. Dynamic ST-segment changes and T-wave changes that accompany episodes of angina pectoris and disappear thereafter are more specific. Variant angina—that is, angina that results from coronary vasospasm rather than occlusive coronary artery disease—is diagnosed by ST-segment elevation during an episode of angina pectoris.
Exercise ECG is useful for detecting signs of myocardial ischemia and establishing their relationship to chest pain. The test also provides information about exercise capacity. Exercise testing is often combined with imaging studies (nuclear, echocardiographic, or magnetic resonance imaging [MRI]) to demonstrate areas of ischemic myocardium. Exercise testing is not always feasible, however, because of the inability of a patient to exercise owing to peripheral vascular or musculoskeletal disease, deconditioning, dyspnea on exertion, prior stroke, or the presence of chest pain at rest or with minimal activity. The presence of conditions that interfere with interpretation of the exercise ECG (e.g., paced rhythm, left ventricular hypertrophy, digitalis administration, or a preexcitation syndrome) also limit the utility of exercise stress testing. The risk of MI related to exercise testing is about 2/10,000 tests and death is 1/10,000. Contraindications to exercise stress testing include rest angina with 48 hours, unstable rhythm, severe aortic stenosis, severe hypertension, acute myocarditis, uncontrolled heart failure, severe pulmonary hypertension, and active infective endocarditis.
The exercise ECG is most likely to indicate myocardial ischemia when there is at least 1 mm of horizontal or downsloping ST-segment depression during or within 4 minutes after exercise. The greater the degree of ST-segment depression, the greater the likelihood of significant coronary artery disease. When the ST-segment abnormality is associated with angina pectoris and occurs during the early stages of exercise and persists for several minutes after exercise, significant coronary artery disease is likely. Exercise ECG is less accurate but more cost effective than imaging tests for detecting ischemic heart disease. A negative stress test result does not exclude the presence of coronary artery disease, but it makes the likelihood of three-vessel or left main coronary disease extremely low. Exercise ECG is less sensitive (overall sensitivity ∼75%) and specific in detecting ischemic heart disease than nuclear cardiology techniques.
Nuclear cardiology techniques
Nuclear stress imaging is useful for assessing coronary perfusion. It has greater sensitivity for detection of ischemic heart disease than exercise testing alone. It can define vascular regions in which stress-induced coronary blood flow is limited and can estimate left ventricular systolic size and function. Tracers such as thallium and technetium can be detected over the myocardium by single-photon emission computed tomography (SPECT) techniques. Recent data also suggest positron emission tomography (PET) imaging (with exercise or pharmacologic stress) using N-13 ammonia or rubidium-82 nuclide as another technique for assessing perfusion. A significant coronary obstructive lesion causes a reduction in blood flow, and thus less tracer activity is present in that area. Exercise increases the difference in tracer activity between normal and underperfused regions because coronary blood flow increases markedly with exercise except in those regions distal to a coronary artery obstruction. Imaging is carried out in two phases: The first is immediately after cessation of exercise to detect regional ischemia, and the second is hours later to detect reversible ischemia. Areas of persistently absent uptake signify an old MI. The size of the perfusion abnormality is the most important indicator of the significance of the coronary artery disease detected.
Alternative methods of exercise testing are available when exercise ECG is not possible or interpretation of ST-segment changes would be difficult. Administration of atropine, infusion of dobutamine, or institution of artificial cardiac pacing produces a rapid heart rate to create cardiac stress. Alternatively, cardiac stress can be produced by administering a coronary vasodilator such as adenosine or dipyridamole. These drugs dilate normal coronary arteries but evoke minimal or no change in the diameter of atherosclerotic coronary arteries. After cardiac stress is induced by these interventions, radionuclide tracer scanning is performed to assess myocardial perfusion.
Echocardiography
Echocardiographic regional wall motion analysis can be performed immediately after stressing the heart either pharmacologically or with exercise. Stress echocardiography is more sensitive than exercise electrocardiography in the diagnosis of ischemic heart disease. New ventricular wall motion abnormalities induced by stress correspond to sites of myocardial ischemia, thereby localizing obstructive coronary lesions. In contrast, exercise ECG can indicate only the presence of ischemic heart disease but does not reliably predict the location of the obstructive coronary lesion. One can also visualize global wall motion under baseline conditions and under cardiac stress. Valvular function can be assessed as well. Limitations imposed by poor visualization have been improved by newer contrast-assisted technologies.
Stress cardiac MRI
Pharmacologic stress imaging with cardiac MRI compares favorably with other methods and is being used clinically. Cardiac magnetic resonance stress testing with dobutamine infusion can be used to assess wall motion abnormalities accompanying ischemia, as well as myocardial perfusion.
Electron beam CT
Calcium deposition occurs in atherosclerotic blood vessels. Coronary artery calcification can be detected by electron beam CT (EBCT) and multidetector CT (MDCT). Although the sensitivity, specificity, and negative predictive values are high (>90%), its routine use has not been clarified.
CT angiography
The heart and coronary arteries can be visualized with contrast medium and multislice CT scanning. This modality is most useful in ruling out coronary artery disease in patients with a low likelihood for significant coronary artery disease. The role of CT angiography in routine clinical practice has yet to be defined.
Coronary angiography
Coronary angiography provides the best information about the condition of the coronary arteries. It is indicated in patients with known or possible angina pectoris who have survived sudden cardiac death, those who continue to have angina pectoris despite maximal medical therapy, those who are being considered for coronary revascularization, those who develop a recurrence of symptoms after coronary revascularization, those with chest pain of uncertain cause, and those with a cardiomyopathy of unknown cause. It can also be used for the definitive diagnosis of coronary disease for occupational reasons (e.g., in airline pilots). Coronary angiography is also useful for establishing the diagnosis of nonatherosclerotic coronary artery disease, such as coronary artery spasm, Kawasaki disease, radiation-induced vasculopathy, and primary coronary artery dissection. A narrowing of coronary luminal diameter by 50% is considered hemodynamically and clinically significant. Intravascular ultrasound is an invasive diagnostic method to determine the extent of intraluminal disease when the angiogram is equivocal. It can also help assess the results of angioplasty or stenting.
The important prognostic determinants in patients with coronary artery disease are the anatomic extent of the atherosclerotic disease, the state of left ventricular function (ejection fraction), and the stability of the coronary plaque. Left main coronary artery disease is the most dangerous anatomic lesion and is associated with an unfavorable prognosis when managed with medical therapy alone. A stenosis of greater than 50% of the left main coronary artery is associated with an annual mortality rate of 15%.
Unfortunately, coronary angiography cannot predict which plaques are most likely to rupture and initiate acute coronary syndromes. Vulnerable plaques (i.e., those most likely to rupture and form an occlusive thrombus) have a thin fibrous cap and a large lipid core containing a large number of macrophages. The presence of vulnerable plaque predicts a greater risk of MI regardless of the degree of coronary artery stenosis. Indeed, AMI most often results from rupture of a plaque that had produced less than 50% stenosis of a coronary artery. Currently there is no satisfactory test to measure the stability of plaques.
Treatment
Comprehensive management of ischemic heart disease has five aspects: (1) identification and treatment of diseases that can precipitate or worsen myocardial ischemia, (2) reduction of risk factors for progression of coronary artery disease, (3) lifestyle modification, (4) pharmacologic management of angina, and (5) revascularization by coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) with or without placement of intracoronary stents. The goal of treatment of patients with chronic stable angina is to achieve complete or almost complete elimination of anginal chest pain and a return to normal activities with minimal side effects.
Treatment of associated diseases
Conditions that increase oxygen demand or decrease oxygen delivery may contribute to an exacerbation of previously stable angina. These conditions include fever, infection, anemia, tachycardia, thyrotoxicosis, heart failure, and cocaine use. Treatment of these conditions is critical to the management of stable ischemic heart disease.
Reduction of risk factors and lifestyle modification
The progression of atherosclerosis may be slowed by cessation of smoking, maintenance of an ideal body weight by consumption of a low-fat, low-cholesterol diet, regular aerobic exercise, and treatment of hypertension. Hypercholesterolemia is an important modifiable risk factor and should be controlled by diet and/or drugs such as statins. Drug treatment is strongly recommended in patients with clinical atherosclerosis or when the low-density lipoprotein (LDL) cholesterol level exceeds 160 mg/dL (goal is >50% reduction or <70 mg/dL). Hypertension increases the risk of coronary events as a result of direct vascular injury, left ventricular hypertrophy, and increased myocardial oxygen demand. Lowering the blood pressure from hypertensive levels to normal levels decreases the risk of MI, congestive heart failure, and stroke. In combination with lifestyle modifications, an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB), β blockers, and calcium channel blockers are especially useful in managing hypertension in patients with angina pectoris.
Medical treatment of myocardial ischemia
Pharmacotherapy for ischemic heart disease is designed to reduce the frequency of anginal episodes, MI, and coronary death. Antiplatelet drugs, nitrates, β blockers, ranolazine, calcium channel blockers, and ACE inhibitors are used in the medical treatment of angina pectoris.
Antiplatelet drugs are widely used in the management of ischemic heart disease: aspirin, thienopyridines (clopidogrel and prasugrel), reversible platelet inhibitors (cangrelor and ticagrelor), and platelet glycoprotein IIb/IIIa inhibitors (eptifibatide, tirofiban, and abciximab). (See Chapter 23 for a detailed discussion of platelet inhibition.)
Aspirin inhibits the enzyme cyclooxygenase-1 (COX-1). This results in inhibition of thromboxane A 2 , which plays an important role in platelet aggregation. This inhibition is irreversible, lasts for the duration of platelet life span (≈7 days), and can be produced by low dosages of aspirin. Daily aspirin therapy (75–325 mg/d) decreases the risk of cardiac events in patients with stable or unstable angina pectoris and is recommended for all patients with ischemic heart disease. Clopidogrel inhibits the adenosine diphosphate (ADP) receptor P2Y 12 and inhibits platelet aggregation in response to ADP release from activated platelets. Clopidogrel-induced inhibition of ADP receptors is irreversible and also lasts for the duration of the platelet’s life span. Seven days after cessation of this drug, 80% of platelets will have recovered normal aggregation function. Clopidogrel is a prodrug that is metabolized into an active compound in the liver. Owing to genetic differences in the enzymes that metabolize clopidogrel to the active drug, significant variability in its activity has been observed. By some estimates, 10% to 20% of patients taking clopidogrel demonstrate resistance or hyperresponsiveness. Furthermore, some drugs (e.g., proton pump inhibitors) can affect the enzyme that metabolizes clopidogrel to its active compound and thereby can reduce the effectiveness of clopidogrel. Clopidogrel can be used in patients who have a contraindication to or are intolerant of aspirin. Prasugrel also inhibits the ADP P2Y 12 receptor irreversibly. However, the pharmacokinetics of prasugrel are more predictable. It is rapidly absorbed, has a faster onset of action, and demonstrates less individual variability in platelet responses compared with clopidogrel. It also is more potent than clopidogrel, and a higher risk of bleeding has been associated with its use. Ticagrelor and its equipotent metabolite reversibly interact with the platelet P2Y 12 ADP receptor, thereby preventing signal transduction and platelet activation and aggregation. Though ticagrelor and prasugrel have been shown to be more effective after ACS or stent placement, they are associated with an increased risk of bleeding. Platelet glycoprotein IIb/IIIa receptor antagonists (abciximab, eptifibatide, tirofiban) inhibit platelet activation, adhesion, and aggregation. Limited-term administration of antiplatelet drugs is particularly useful after placement of an intracoronary stent.
Organic nitrates decrease the frequency, duration, and severity of angina pectoris and increase the amount of exercise required to produce ST-segment depression. The antianginal effects of nitrates are greater when these drugs are used in combination with β blockers or calcium channel blockers. Nitrates dilate coronary arteries and collateral blood vessels and thereby improve coronary blood flow. The venodilating effect of nitrates decreases venous return and hence left ventricular preload, left ventricular end-diastolic volume, and pressure, thereby reducing myocardial wall tension and myocardial oxygen consumption. Nitrates also decrease peripheral vascular resistance, which reduces left ventricular afterload and myocardial oxygen consumption. They also have potential antithrombotic effects. Nitrates are contraindicated in the presence of hypertrophic cardiomyopathy or severe aortic stenosis and should not be used within 24 hours of sildenafil, tadalafil, or vardenafil use because this combination may produce severe hypotension. Administration of sublingual nitroglycerin by tablet or spray produces prompt relief of angina pectoris. The most common side effect of nitrate treatment is headache. Hypotension may occur after nitrate administration in hypovolemic patients. For long-term therapy, long-acting nitrate preparations (e.g., isosorbide tablets and nitroglycerin ointment or patches) are equally effective. The therapeutic value of organic nitrates can be compromised by the development of tolerance. To avoid nitrate tolerance, a daily 8- to 12-hour interval free of nitrate exposure is recommended.
β blockers are the only drugs that have been shown to prolong life in patients with coronary artery disease. They have antiischemic, antihypertensive, and antidysrhythmic properties. Long-term administration of β blockers decreases the risk of death and myocardial reinfarction in patients who have had an MI, presumably by decreasing myocardial oxygen demand. This benefit is present even in patients in whom β blockers were traditionally thought to be contraindicated, such as those with congestive heart failure, pulmonary disease, or advanced age. Drug-induced blockade of β 1 -adrenergic receptors by atenolol, metoprolol, acebutolol, or bisoprolol results in heart rate slowing and decreased myocardial contractility that are greater during activity than at rest. The result is a decrease in myocardial oxygen demand with a subsequent decrease in ischemic events during exertion. The decrease in heart rate also increases the length of diastole and thus coronary perfusion time. Non-specific-adrenergic blockers (propranolol, nadolol) can increase the risk of bronchospasm in patients with reactive airway disease. Despite differences between β 1 and β 2 effects, all β blockers seem to be equally effective in the treatment of angina pectoris. The most common side effects of β blocker therapy are fatigue and insomnia. Heart failure may be intensified. β blockers are contraindicated in the presence of severe bradycardia, sick sinus syndrome, severe reactive airway disease, second- or third-degree atrioventricular heart block, and uncontrolled congestive heart failure. Diabetes mellitus is not a contraindication to β blocker therapy, although these drugs may mask signs of hypoglycemia. Abrupt withdrawal of β blockers after prolonged administration can worsen ischemia in patients with chronic stable angina.
Long-acting calcium channel blockers are comparable to β blockers in relieving anginal pain. However, short-acting calcium channel blockers such as verapamil and nifedipine are not. Diltiazem can be combined with β blockers in patients with normal left ventricular function and no conduction defects. Calcium channel blockers are uniquely effective in decreasing the frequency and severity of angina pectoris due to coronary artery spasm (Prinzmetal or variant angina). They are not as effective as β blockers in decreasing the incidence of myocardial reinfarction. The effectiveness of calcium channel blockers is due to their ability to decrease vascular smooth muscle tone, dilate coronary arteries, decrease myocardial contractility and myocardial oxygen consumption, and decrease systemic blood pressure. Many calcium channel blockers such as amlodipine, nicardipine, isradipine, felodipine, and long-acting nifedipine are potent vasodilators and are useful in treating both hypertension and angina. Amlodipine and β blockers have complimentary actions. Common side effects of calcium channel blocker therapy include hypotension, peripheral edema, and headache. Calcium channel blockers are contraindicated in patients with severe congestive heart failure or severe aortic stenosis. They must be used cautiously if given in combination with β blockers because both classes of drugs have significant depressant effects on heart rate and myocardial contractility.
Ranolazine is a cardioselective antiischemic agent. It interacts with sodium and potassium channels and inhibits late inward sodium current in cardiac myocytes. It is indicated for chronic angina only, when standard medical therapy has failed to control angina, and should not be used for the management of acute episodes of angina pectoris. It is excreted by the kidney and can cause significant QTc prolongation and should be avoided in patients with kidney and/or liver disease.
Excessive angiotensin II plays a significant role in the pathophysiology of cardiac disorders. It can lead to development of myocardial hypertrophy, interstitial myocardial fibrosis, increased coronary vasoconstriction, and endothelial dysfunction. Angiotensin II also promotes inflammatory responses and atheroma formation. ACE inhibitors are important not only in the treatment of heart failure but also in the treatment of hypertension and in cardiovascular protection. ACE inhibitors are recommended for patients with coronary artery disease, especially those with hypertension, left ventricular dysfunction, or diabetes mellitus. ARBs offer similar benefits. Contraindications to ACE inhibitor use include documented intolerance or allergy, hyperkalemia, bilateral renal artery stenosis, and renal failure.
Revascularization
Revascularization by CABG or PCI with or without placement of intracoronary stents is indicated when optimal medical therapy fails to control angina pectoris. Revascularization is also indicated for specific anatomic lesions, in particular left main coronary artery stenosis of more than 50% or 70% or greater stenosis in an epicardial coronary artery. Revascularization is also indicated in patients with significant coronary artery disease with evidence of impaired left ventricular contractility (ejection fraction <40%). However, the presence of hypokinetic or akinetic areas in the left ventricle connotes a poor prognosis. Extensive myocardial fibrosis from a prior MI is unlikely to be improved by revascularization. However, some patients with ischemic heart disease have chronically impaired myocardial function (hibernating myocardium) that demonstrates improvement in contractility after surgical revascularization. In patients with stable angina pectoris and significant one- or two-vessel coronary artery disease, a PCI, with or without stent placement, or surgical CABG may be used for revascularization. CABG is preferred over PCI in patients with significant left main coronary artery disease, those with three-vessel coronary artery disease, and patients with diabetes mellitus who have two- or three-vessel coronary artery disease. Operative mortality rates for CABG surgery currently range from 1.5% to 2% in younger patients but increase to 4% to 8% in older individuals (>80 years) and in those who have had prior CABG.
Acute coronary syndrome
ACS represents an acute or worsening imbalance of myocardial oxygen supply to demand. It typically occurs as a result of focal disruption of an atheromatous plaque that triggers the coagulation cascade, with subsequent generation of thrombin and partial or complete occlusion of the coronary artery by a thrombus. Rarely it may result from prolonged coronary vasospasm, embolic occlusion, vasculitis, or aortic root/coronary artery dissection. Imbalance of myocardial oxygen supply and demand leads to ischemic chest pain. ACS can be classified into three categories based on the findings of a 12-lead ECG and the levels of cardiac-specific biomarkers (troponins). Patients with ST elevation at presentation are considered to have STEMI. Patients who have ST-segment depression or nonspecific changes on the ECG are categorized based on the levels of cardiac-specific troponins or myocardial creatine kinase (CK)-MB. Elevation of cardiac-specific biomarker levels in this situation indicates NSTEMI. If levels of cardiac-specific biomarkers are normal, unstable angina is present ( Fig. 5.2 ). STEMI and UA/NSTEMI syndromes are managed differently and have different prognoses. Many more patients have UA/NSTEMI than have STEMI at presentation.
ST-segment elevation myocardial infarction
Mortality rates from STEMI have declined steadily because of early therapeutic interventions such as angioplasty, thrombolysis and aspirin, heparin, and statin therapy. However, the mortality rate of acute STEMI remains significant. In-hospital mortality rate after admission for AMI has declined from 10% to 5% over the past decade. One-year mortality rate is about 15%. Advanced age (>75 years) consistently emerges as one of the principal determinants of early mortality in patients with STEMI. Coronary angiography has documented that the majority of STEMIs are caused by thrombotic occlusion of a coronary artery. In rare cases STEMI may be due to coronary occlusion caused by coronary emboli, congenital abnormalities, coronary spasm, or inflammatory diseases.
The long-term prognosis after an acute STEMI is determined principally by the severity of residual left ventricular dysfunction, the presence and degree of residual ischemia, and the presence of malignant ventricular dysrhythmias. Most deaths that occur during the first year after hospital discharge take place within the first 3 months. Ventricular function can be substantially improved during the first few weeks after an AMI, particularly in patients in whom early reperfusion is achieved. Therefore measurement of ventricular function 2 to 3 months after an MI is a more accurate predictor of long-term prognosis than measurement of ventricular function during the acute phase of the infarction.
Pathophysiology
Atherosclerosis is recognized as an inflammatory disease. The presence of inflammatory cells in atherosclerotic plaques suggests that inflammation is important in the cascade of events leading to plaque rupture. Indeed, serum markers of inflammation such as C-reactive protein and fibrinogen are increased in those at greatest risk of developing coronary artery disease.
STEMI occurs when coronary blood flow decreases abruptly. This decrease in blood flow is attributable to acute thrombus formation at a site where an atherosclerotic plaque fissures, ruptures, or ulcerates. This creates a local environment that favors thrombogenesis. Typically, vulnerable plaques (i.e., those with rich lipid cores and thin fibrous caps) are most prone to rupture. A platelet monolayer forms at the site of ruptured plaque, and various chemical mediators such as collagen, ADP, epinephrine, and serotonin stimulate platelet aggregation. The potent vasoconstrictor thromboxane A 2 is released, which further compromises coronary blood flow. Glycoprotein IIb/IIIa receptors on the platelets are activated, which enhances the ability of platelets to interact with adhesive proteins and other platelets and causes growth and stabilization of the thrombus. Further activation of coagulation leads to strengthening of the clot by fibrin deposition. This makes the clot more resistant to thrombolysis. It is rather paradoxical that plaques that rupture and lead to acute coronary occlusion are rarely of a size that causes significant coronary obstruction. By contrast, flow-restrictive plaques that produce chronic stable angina and stimulate development of collateral circulation are less likely to rupture.
Diagnosis
Criteria for the definition of an AMI have been revised ( Table 5.3 ). Now this diagnosis requires detection of a rise and/or fall in cardiac biomarkers (preferably troponin with at least one value above the 99th percentile of the upper reference limit) and evidence of myocardial ischemia by one of the following: (1) symptoms of ischemia; (2) ECG changes indicative of new ischemia, such as new ST-T changes or new left bundle branch block (LBBB); (3) development of pathologic Q waves on the ECG; (4) imaging evidence of a new loss of viable myocardium or a new regional wall motion abnormality; or (5) identification of an intracoronary thrombus by angiography or autopsy. Contemporary studies using MRI suggest that the development of a Q wave on the ECG is more dependent on the volume of the infarcted tissue than the transmurality of the infarction.
TABLE 5.3
Criteria for Diagnosis of Acute Myocardial Infarction
From Thygesen K, et al. Fourth universal definition of myocardial infarction (2018). Eur Heart J. 2019;40(3):237–269.
The term myocardial infarction should be used when there is evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Under these conditions any one of the following criteria meets the diagnosis for myocardial infarction:
|
Almost two-thirds of patients describe new-onset angina pectoris or a change in their anginal pattern during the 30 days preceding an AMI. The pain is often more severe than the previous angina pectoris and does not resolve with rest. It may radiate as high as the occipital area but not below the umbilicus. Other potential causes of severe chest pain (pulmonary embolism, aortic dissection, spontaneous pneumothorax, pericarditis, cholecystitis) should be considered. About a quarter of patients, especially the elderly and those with diabetes, have no or only mild pain at the time of AMI. Sometimes STEMI may masquerade as acute heart failure, syncope, stroke, or shock, with the patient’s ECG showing ST-segment elevation or a new LBBB.
On physical examination, patients typically appear anxious, pale, and diaphoretic. Sinus tachycardia is usually present. Hypotension caused by left or right ventricular dysfunction or cardiac dysrhythmias may be present. Rales signal congestive heart failure due to left ventricular dysfunction. A cardiac murmur may indicate ischemic mitral regurgitation.
Laboratory studies.
Troponin is a cardiac-specific protein and biochemical marker for AMI. An increase in the circulating concentration of troponin occurs early after myocardial injury. Levels of cardiac troponins (troponin T or I) increase within 3 hours after myocardial injury and remain elevated for 7 to 10 days. Elevated troponins and the ECG are powerful predictors of adverse cardiac events in patients with anginal pain. Troponin is more specific than CK-MB for determining myocardial injury. The currently accepted definition of AMI recommends assessing the magnitude of the infarction by measuring how much the cardiac biomarker level is elevated above the normal reference range ( Fig. 5.3 ).
Imaging studies.
Patients with typical ECG evidence of AMI do not require evaluation with echocardiography. However, echocardiography is useful in patients with LBBB or an abnormal ECG in whom the diagnosis of AMI is uncertain and in patients with suspected aortic dissection. Echocardiography will demonstrate regional wall motion abnormalities in most patients with AMI. The time required to perform myocardial perfusion imaging and the inability to differentiate between new and old MI limits the utility of radionuclide imaging in the early diagnosis of AMI.
Treatment
Early treatment of AMI reduces morbidity and mortality. Initial steps include administering oxygen to all patients. Pain relief, usually provided by intravenous (IV) morphine and/or sublingual nitroglycerin, is necessary to reduce catecholamine release and the resultant increase in myocardial oxygen requirements. All patients with suspected or definite AMI should receive aspirin. Patients with allergy to aspirin should receive a P2Y 12 inhibitor (clopidogrel, prasugrel, or ticagrelor). The combination of aspirin and P2Y 12 inhibitors improves outcomes. Alternatively, platelet glycoprotein IIb/IIIa inhibitors can be used even if urgent CABG is likely. Unfractionated heparin is frequently used in combination with antiplatelet drugs, especially if thrombolytic therapy or PCI is planned. β blockers relieve ischemic chest pain, infarct size, and life-threatening dysrhythmias. β blockers are administered to patients in hemodynamically stable condition who are not in heart failure, not in a low cardiac output state, and not at risk of cardiogenic shock. β blockers are not given to those with heart block. The primary goal in management of STEMI is to reestablish blood flow in the obstructed coronary artery as soon as possible. This can be achieved by thrombolytic therapy or PCI. The time from the onset of symptoms to reperfusion strongly influences the outcome of an acute STEMI. Glucocorticoids and other nonsteroidal antiinflammatory drugs (NSAIDs) should be avoided (except for aspirin) in patients with STEMI.
Reperfusion therapy.
Thrombolytic therapy with tissue plasminogen activator (tPA), streptokinase, reteplase, or tenecteplase should be initiated within 30 to 60 minutes of hospital arrival and within 12 hours of symptom onset. Thrombolytic therapy restores normal antegrade blood flow in the occluded coronary artery. Dissolution of the clot by thrombolytic therapy becomes much more difficult if therapy is delayed. The most feared complication of thrombolytic therapy is intracranial hemorrhage. This is most likely in elderly patients (>75 years) and in those with uncontrolled hypertension. Patients who have gastrointestinal bleeding or have recently undergone surgery are also at increased risk of bleeding complications with thrombolysis. Contraindications to fibrinolytic therapy include uncontrolled hypertension (systolic >180 mm Hg and/or diastolic >110 mm Hg), hemorrhagic strokes within the previous year, known intracranial neoplasm, recent head trauma, active or recent internal bleeding (within 3 weeks), or suspected aortic dissection.
Percutaneous coronary intervention.
PCI may be preferable to thrombolytic therapy for restoring flow to an occluded coronary artery if appropriate resources are available. Ideally, angioplasty should be performed within 90 minutes of arrival at the healthcare facility and within 12 hours of symptom onset. It is the treatment of choice in patients with a contraindication to thrombolytic therapy, in those with severe heart failure and/or pulmonary edema, when symptoms have been present for at least 2 to 3 hours, or when the clot becomes more mature and less likely to be lysed by fibrinolytic drugs. The combined use of intracoronary stents and antiplatelet drugs during emergency PCI provides the maximum chance of achieving normal antegrade coronary blood flow and decreases the need for a subsequent revascularization procedure. In some patients an integrated reperfusion strategy is adopted where fibrinolytic therapy is followed later by coronary angiography if there is evidence of persistent ischemia (rescue PCI) or inducible ischemia (urgent PCI).
Coronary artery bypass graft surgery.
CABG can restore blood flow in an occluded coronary artery, but reperfusion is achieved faster with thrombolytic therapy or coronary angioplasty. Emergency CABG is reserved for patients in whom angiography reveals coronary anatomy that precludes PCI, patients with a failed angioplasty, and those with evidence of infarction-related ventricular septal rupture or mitral regurgitation. Patients with ST-segment elevation who develop cardiogenic shock, LBBB, or a posterior wall MI within 36 hours of an acute STEMI are also candidates for early revascularization. Mortality from CABG is significant during the first 3 to 7 days after AMI.
Adjunctive medical therapy
Antithrombotic agents.
IV heparin therapy is commonly administered after thrombolytic therapy to decrease the risk of thrombus regeneration. A disadvantage of unfractionated heparin is the variability in the dose response due to its binding with plasma proteins other than antithrombin. Low-molecular-weight heparin (LMWH) provides a more predictable pharmacologic effect, a long plasma half-life, and a more practical means of administration (subcutaneous), without the need to monitor the activated partial thromboplastin time. Thus LMWH is an excellent alternative to unfractionated heparin. Direct thrombin inhibitors such as bivalirudin can be used in patients with a history of heparin-induced thrombocytopenia.
β blockers.
Administration of β blockers is associated with a significant decrease in early (in-hospital) and long-term mortality and myocardial reinfarction. Early administration of β blockers can decrease infarct size by decreasing heart rate, blood pressure, and myocardial contractility and improving the myocardial oxygen supply-demand relationship. In the absence of specific contraindications, it is recommended that patients receive β blockers as early as possible after AMI. β blocker therapy should be continued indefinitely.
Inhibition of the renin-angiotensin-aldosterone system.
ACE inhibitors decrease the mortality rate after STEMI, and the mortality benefits are additive to those achieved with aspirin and β blockers. All patients with a large anterior wall MI, clinical evidence of left ventricular failure, an ejection fraction less than 40%, or diabetes should be treated with ACE inhibitors or angiotensin II receptor blockers. Barring significant renal dysfunction or hyperkalemia, aldosterone blockade should also be considered in this patient population.
You're Reading a Preview
Become a Clinical Tree membership for Full access and enjoy Unlimited articles
If you are a member. Log in here
