Myocardial Infarction

Myocardial infarction, commonly known as a heart attack, is the irreversible necrosis of heart muscle secondary to prolonged ischemia. This usually results from an imbalance in oxygen supply and demand, which is most often caused by plaque rupture with thrombus formation in a coronary vessel, resulting in an acute reduction of blood supply to a portion of the myocardium. (See Etiology.) The electrocardiographic results of an acute myocardial infarction are seen below.

Although the clinical presentation of a patient is a key component in the overall evaluation of the patient with myocardial infarction, many events are either "silent" or are clinically unrecognized, evidencing that patients, families, and health care providers often do not recognize symptoms of a myocardial infarction. (See Clinical Presentation.) The appearance of cardiac markers in the circulation generally indicates myocardial necrosis and is a useful adjunct to diagnosis. (See Workup.)

Myocardial infarction is considered part of a spectrum referred to as acute coronary syndrome (ACS). The ACS continuum representing ongoing myocardial ischemia or injury consists of unstable angina, non–ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI). Patients with ischemic discomfort may or may not have ST-segment or T-wave changes denoted on the electrocardiogram (ECG). ST elevations seen on the ECG reflect active and ongoing transmural myocardial injury. Without immediate reperfusion therapy, most persons with STEMI develop Q waves, reflecting a dead zone of myocardium that has undergone irreversible damage and death.

Those without ST elevations are diagnosed either with unstable angina or NSTEMI―differentiated by the presence of cardiac enzymes. Both these conditions may or may not have changes on the surface ECG, including ST-segment depression or T-wave morphological changes.

Myocardial infarction may lead to impairment of systolic or diastolic function and to increased predisposition to arrhythmias and other long-term complications.

Coronary thrombolysis and mechanical revascularization have revolutionized the primary treatment of acute myocardial infarction, largely because they allow salvage of the myocardium when implemented early after the onset of ischemia. (See Treatment Strategies and Management.)

The modest prognostic benefit of an opened infarct-related artery may be realized even when recanalization is induced only 6 hours or more after the onset of symptoms, that is, when the salvaging of substantial amounts of jeopardized ischemic myocardium is no longer likely. The opening of an infarct-related artery may improve ventricular function, collateral blood flow, and ventricular remodeling, and it may decrease infarct expansion, ventricular aneurysm formation, left ventricular dilatation, late arrhythmia associated with ventricular aneurysms, and mortality.[4, 5, 6, 7, 8]

Evidence suggests a benefit from the use of beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, and statins.

The American College of Cardiology (ACC)/American Heart Association (AHA)/European Society of Cardiology/World Heart Federation released the Observations From the TRITON-TIMI 38 Trial (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis in Myocardial Infarction 38), which better outlines a universal definition of myocardial infarction, along with a classification system and risk factors for cardiovascular death.[9]

The right and left coronary arteries most often arise independently from individual ostia in association with the right and left aortic valve cusps.

The left anterior descending (LAD) and left circumflex (LCX) coronary arteries arise at the left main coronary artery bifurcation; they supply the anterior LV, the bulk of the interventricular septum (anterior two thirds), the apex, and the lateral and posterior LV walls. The right coronary artery (RCA) generally supplies the right ventricle (RV), the posterior third of the interventricular septum, the inferior wall (diaphragmatic surface) of the left ventricle (LV), and a portion of the posterior wall of the LV (by means of the posterior descending branch).

When the posterior descending coronary artery (PDA), which supplies the posterior interventricular septum, arises from the LCX artery, the circulation is called left dominant. Most often, the PDA arises from the RCA; this anatomy is called right-dominant circulation.

In two thirds of patients, the first branch of the RCA is the conus artery, which supplies the conus arteriosus (RV outflow tract); occasionally the conus arteriosus arises from a separate orifice.

In 60% of patients, the sinus node artery arises from the proximal RCA, and in 40% of patients, it arises from the LCX artery. The anterior branches supply the free wall of the RV, and the acute marginal branches supply the RV. When the RCA extends to the crux (the origin of the PDA), it supplies the atrioventricular (AV) node (90%); otherwise, the AV node is supplied by the LCX.

Therefore, obstruction of the RCA commonly affects the sinus node and the AV node, resulting in bradycardia, with or without heart block. Not surprisingly, RCA occlusion frequently manifests with sinus bradycardia, AV block, RV myocardial infarction, and/or inferoposterior myocardial infarction (of the LV). (See Etiology.)

The spectrum of myocardial injury depends not only on the intensity of impaired myocardial perfusion but also on the duration and the level of metabolic demand at the time of the event. The damage in the myocardium is essentially the result of a tissue response that includes apoptosis (cell death) and inflammatory changes. Therefore, the hearts of patients who suddenly die from an acute coronary event may show little or no evidence of damage response to the myocardium at autopsy.

The typical myocardial infarction initially manifests as coagulation necrosis that is ultimately followed by myocardial fibrosis. Contraction-band necrosis is also seen in many patients with ischemia. This is followed by reperfusion, or it is accompanied by massive adrenergic stimulation, often with concomitant myocytolysis.

The left coronary artery system covers more territory than does the right system; therefore, a myocardial infarction in this system is most likely to produce extensive injury, with impairment of function, pulmonary congestion, and low output. Occlusion of the left coronary artery may also cause a left anterior hemiblock or a left posterosuperior hemiblock conduction abnormality; these effects are evidenced by a change of frontal axis on the electrocardiogram (ECG). (See Electrocardiogram.)

Inferior-wallmyocardial infarctionand right ventricularmyocardial infarction

In severe cases of acute inferior-wall myocardial infarction with RV involvement, the forward delivery of blood from the RV to the LV may be insufficient to fill the LV, resulting in low blood pressure even if the LV is intact. (See Physical Examination.)

Chemoreceptor activation in the myocardium actuates vagal (parasympathetic) efferent discharge, known as the Bezold-Jarisch reflex, which causes bradycardia and vessel dilation that may further lower blood pressure. Adenosine may accumulate in the infarct zone secondary to a local inhibition of adenosine deaminase, for which aminophylline may act pharmacologically as an antagonist. The hemodynamic changes resemble many of those seen with pericardial constriction or tamponade. Patients with this condition respond well to an infusion of normal sodium chloride solution. Improvement with such infusion compensates for failure of the pumping action of the RV; it reduces vagal tone, and it deactivates the pressure sensors that were sending a hormonal signal to the kidneys to retain salt.

Arrhythmogenesis

In addition to the direct effects of ischemia and tissue hypoxia, decreased removal of noxious metabolites, including potassium, calcium, amphophilic lipids, and oxygen-centered free radicals, also impair ventricular performance. These abnormalities promote potentially lethal arrhythmias.

Pericarditis

Epicardial inflammation may initiate pericarditis, which is seen in more than 20% of patients presenting with Q-wave infarctions.

Reduced systolic function

Lack of adequate oxygen and insufficient metabolite delivery to the myocardium diminish the force of muscular contraction and decrease systolic wall motion in the affected territory.

Abnormal regional wall motion

Even brief deprivation of oxygen and the requisite metabolites to the myocardium diminishes diastolic relaxation and causes abnormal regional systolic contractile function, wall thickening, and abnormal wall motion. If the area affected is extensive, diminished stroke volume and cardiac output may result.

Hypokinesis and akinesis

In general, regions of hypokinesis and akinesis of the ventricular myocardium reflect the location and extent of myocardial injury.

Myocardial infarctionexpansion

In general, expansion of infarcted myocardium and resultant ventricular dilatation (ie, ventricular remodeling) ensues within a few hours after the onset of a myocardial infarction. An expanding myocardial infarction leads to thinning of the infarct zone and realignment of layers of tissue in and adjacent to it, causing ventricular dilatation.

Myocardial rupture

Myocardial rupture was seen in as many as 10% of fatal myocardial infarctions before the era of thrombolytic agents, but it is now encountered much less often. When rupture occurs, it may be associated with large infarctions; indications include cardiogenic shock or hemodynamically significant arrhythmia. Patients may have a history of hypertension with ventricular hypertrophy.

Ventricular aneurysm

A ventricular aneurysm is an outward bulging of a noncontracting segment. In the early days of cardiac imaging, ventricular aneurysms were seen in as many as 20% of patients with Q-wave myocardial infarction, but now it is seen in less than 8%.

Cardiogenic shock

In patients with extensive myocardial injury, coronary blood flow diminishes as cardiac output declines and heart rate accelerates. Because coronary artery disease is usually generalized or diffuse, ischemia that occurs at a distance from the infracted segment may result in a vicious cycle in which a stuttering and expanding myocardial infarction ultimately leads to profound LV failure, hypotension, and cardiogenic shock.

Effect on diastolic function

Immediately after the onset of myocardial infarction, the ability of ischemic myocardium to relax declines. Relaxation is an active process that uses ATP. Impaired relaxation increases LV end-diastolic volume (LVEDV) and LV end-diastolic pressure (LVEDP).

The increased LVEDP results in ventricular dilation, increased pulmonary venous pressure, decreased pulmonary compliance, and interstitial and (ultimately) alveolar pulmonary edema. These effects lead to increased hypoxemia, which may worsen ischemic injury to the myocardium.

Atherosclerosis is the disease primarily responsible for most acute coronary syndrome (ACS) cases. Approximately 90% of myocardial infarctions result from an acute thrombus that obstructs an atherosclerotic coronary artery. Plaque rupture and erosion are considered to be the major triggers for coronary thrombosis. Following plaque erosion or rupture, platelet activation and aggregation, coagulation pathway activation, and endothelial vasoconstriction occur, leading to coronary thrombosis and occlusion.

Within the coronary vasculature, flow dynamics and endothelial shear stress are implicated in the pathogenesis of vulnerable plaque formation.[10] Evidence indicates that in numerous cases, culprit lesions are stenoses of less than 70% and are located proximally within the coronary tree.[11, 12] Coronary atherosclerosis is especially prominent near branching points of vessels.[13] Culprit lesions that are particularly prone to rupture are atheromas containing abundant macrophages, a large lipid-rich core surrounded by a thinned fibrous cap.

Nonmodifiable risk factors for atherosclerosis include the following:

• Age

• Sex

• Family history of premature coronary heart disease

• Male-pattern baldness

Modifiable risk factors for atherosclerosis include the following:

• Smoking or other tobacco use

• Diabetes mellitus

• Hypertension

• Hypercholesterolemia and hypertriglyceridemia, including inherited lipoprotein disorders

• Dyslipidemia

• Obesity

• Sedentary lifestyle and/or lack of exercise

• Psychosocial stress

• Poor oral hygiene

• Type A personality

Elevated homocysteine levels and the presence of peripheral vascular disease are also risk factors for atherosclerosis.

Intramural thrombus development

Inflammation of the endocardial surfaces and stasis of blood flow associated with regional akinesis (no wall motion) or dyskinesis (abnormal, passively reversed wall motion) may lead to the formation of ventricular mural thrombi, which have the potential to embolize.

Patients with acute myocardial infarction are prone to cerebrovascular injury as a result of emboli from ventricular mural thrombi; the rate is approximately 1%.

Causes of myocardial infarction other than atherosclerosis

Nonatherosclerotic causes of myocardial infarction include the following:

• Coronary occlusion secondary to vasculitis

• Ventricular hypertrophy (eg, left ventricular hypertrophy, idiopathic hypertrophic subaortic stenosis [IHSS], underlying valve disease)

• Coronary artery emboli, secondary to cholesterol, air, or the products of sepsis

• Congenital coronary anomalies

• Coronary trauma

• Primary coronary vasospasm (variant angina)

• Drug use (eg, cocaine, amphetamines, ephedrine)

• Arteritis

• Coronary anomalies, including aneurysms of coronary arteries

• Factors that increase oxygen requirement, such as heavy exertion, fever, or hyperthyroidism

• Factors that decrease oxygen delivery, such as hypoxemia of severe anemia

• Aortic dissection, with retrograde involvement of the coronary arteries

• Infected cardiac valve through a patent foramen ovale (PFO)

• Significant gastrointestinal bleed

In addition, myocardial infarction can result from hypoxia due to carbon monoxide poisoning or acute pulmonary disorders. Infarcts due to pulmonary disease usually occur when demand on the myocardium dramatically increases relative to the available blood supply.

Although rare, pediatric coronary artery disease may be seen with Marfan syndrome, Kawasaki disease, Takayasu arteritis, progeria, and cystic medial necrosis.

Imaging studies, such as contrast chest CT scans or transesophageal echocardiograms, should be used to differentiate myocardial infarction from aortic dissection in patients in whom the diagnosis is in doubt. Stanford type A aortic dissections may dissect in a retrograde fashion causing coronary blockage and dissection, which may result in myocardial infarction. In one study, 8% of patients with Stanford type A dissections had ST elevation on ECG. (See Echocardiography.)

Myocardial infarction induced by chest trauma has also been reported, usually following severe chest trauma such as motor vehicle accidents and sports injuries.

Acute myocardial infarction in childhood

Acute myocardial infarction is rare in childhood and adolescence (See Epidemiology). Although adults acquire coronary artery disease from lifelong deposition of atheroma and plaque, which causes coronary artery spasm and thrombosis, children with acute myocardial infarction usually have either an acute inflammatory condition of the coronary arteries or an anomalous origin of the left coronary artery. Intrauterine myocardial infarction also does occur, often in association with coronary artery stenosis.[14]

United States statistics – Incidence and mortality rate

Cardiovascular disease is the leading cause of death in the United States; approximately 500,000-700,000 deaths related to the coronary artery occur each year.

Approximately 1.5 million cases of myocardial infarction occur annually in the United States; the yearly incidence rate is approximately 600 cases per 100,000 people. The proportion of patients diagnosed with NSTEMI compared with STEMI has progressively increased. Despite an impressive decline in age-adjusted death rates attributable to acute myocardial infarction since the mid-1970s, the total number of myocardial infarction-related deaths in the United States has not declined. This may in part be the result of population growth.

Cardiovascular disease is the leading cause of morbidity and mortality among black, Hispanic, and white populations in the United States.

Cardiovascular disease in industrialized and developing nations

Ischemic heart disease is the leading cause of death worldwide.

Cardiovascular diseases cause 12 million deaths throughout the world each year, according to the third monitoring report of the World Health Organization, 1991-93. They cause half of all deaths in several industrialized countries and are one of the main causes of death in many developing countries; they are the major cause of death in adults everywhere.

Of particular concern are projections from the World Heart Federation that the burden of atherosclerotic cardiovascular disease in developing countries will increasingly become commensurate with that seen in industrialized countries. With a decline in infectious disease-related deaths, in conjunction with accelerated economic development and life-style changes that promote atherosclerosis, rates of ischemic heart disease and myocardial infarction are expected to sharply increase in developing countries, especially such countries in Eastern Europe, Asia, and parts of Latin America.

Sex predilection in cardiovascular disease

A male predominance in the incidence of cardiovascular disease exists up to approximately age 70 years, when the sexes converge to equal incidence. Premenopausal women appear to be somewhat protected from atherosclerosis, possibly owing to the effects of estrogen.

Age predilection in cardiovascular disease

The incidence of cardiovascular disease increases with age, with acute myocardial infarction being rare in childhood and adolescence. Most patients who develop an acute myocardial infarction are older than 60 years. Elderly people also tend to have higher rates of morbidity and mortality from their infarcts. Age (≥75 y) is the strongest predictor of 90-day mortality in patients with STEMI undergoing percutaneous coronary intervention.[15] A continued focus on improving outcomes for these high-risk patients is needed.

One third of patients who experience STEMI die within 24 hours of the onset of ischemia, and many of the survivors experience significant morbidity. However, a steady decline has occurred in the mortality rate from STEMI over the last several decades.

Acute myocardial infarction is associated with a 30% mortality rate; half of the deaths occur prior to arrival at the hospital. An additional 5-10% of survivors die within the first year after their myocardial infarction. Approximately half of all patients with a myocardial infarction are rehospitalized within 1 year of their index event.

In a study that assessed the impact of prehospital time on STEMI outcome, Chughatai et al suggest that "total time to treatment" should be used as a core measure instead of "door-to-balloon time."[16] This is because on-scene time was the biggest fraction of "prehospital time." The study compared groups with total time to treatment of more than 120 minutes compared with 120 minutes or less and found mortalities were 4 compared with 0 and transfers to a tertiary care facility were 3 compared with 1, respectively.

Overall, prognosis is highly variable and depends largely on the extent of the infarct, the residual left ventricular function, and whether the patient underwent revascularization.

Better prognosis is associated with the following factors:

• Successful early reperfusion (STEMI goals: patient arrival to fibrinolysis infusion within 30 minutes OR patient arrival to percutaneous coronary intervention within 90 minutes)

• Preserved left ventricular function

• Short-term and long-term treatment with beta-blockers, aspirin, and ACE inhibitors

Poorer prognosis is associated with the following factors:

• Increasing age

• Diabetes

• Previous vascular disease (ie, cerebrovascular disease or peripheral vascular disease)

• Elevated Thrombolysis in Myocardial Infarction (TIMI) risk score for unstable angina/NSTEMI (7 factors: Age ≥65 y, ≥3 risk factors for cardiac disease, previous coronary disease, ST segment deviation ≥0.5 mm, ≥2 episodes of angina in last 24 h, aspirin use within prior wk, and elevated cardiac enzyme levels)[17]

• Delayed or unsuccessful reperfusion

• Poorly preserved left ventricular function (the strongest predictor of outcome)

• Evidence of congestive heart failure (Killip classification ≥II)[18] or frank pulmonary edema (Killip classification ≥III)[19]

• Elevated B-type natriuretic peptide (BNP) levels[20, 21, 22]

• Elevated high sensitive C-reactive protein (hs-CRP), a nonspecific inflammatory marker[23]

• Secretory-associated phospholipase A2 activity is related to atherosclerosis and predicts all-cause mortality in elderly patients; it also predicts mortality or MI in post-MI patients.[24]

A study by Alherbish et al found that in patients with STEMI, the presence of ST deviation in ECG lead aVR indicates an increased mortality risk. Data from the APEX-AMI (Pexelizumab in Conjunction With Angioplasty in Acute Myocardial Infarction) trial were examined to determine the incidence and prognostic value of aVR ST deviation in STEMI patients undergoing primary percutaneous coronary intervention within 6 hours of symptom onset; the investigators determined that aVR ST deviation was associated with a 50% relative increase in the risk of death within 90 days in patients with noninferior MI, whereas aVR ST elevation in patients with inferior MI was associated with a nearly 6-fold increase in such risk.[25, 26]

Blood glucose

Beck et al found that elevated blood glucose level on admission is associated with increased short-term mortality in nondiabetic patients presenting with a first acute myocardial infarction. Analysis of data from a German myocardial infarction registry database showed that among 1,631 nondiabetic acute myocardial infarction patients with admission glucose level more than 152 mg/dL (top quartile), the risk of death within 28 days was higher than among patients in the bottom quartile (odds ratio, 2.82; 95% confidence interval, 1.30-6.12). However, in 659 registry patients with type 2 diabetes, admission glucose levels did not correlate significantly with short-term mortality. Beck et al concluded that nondiabetic acute myocardial infarction patients with elevated glucose levels constitute a high-risk group that requires aggressive intervention.[27]

Psychological depression

The combination of acute myocardial infarction and psychological depression appears to worsen the patient's prognosis. Acute myocardial infarction may precipitate reactive depression whether or not beta-adrenergic blocking agents or other CNS-active agents are administered.

Myocardial hibernation and stunning

After the occurrence of 1 or more ischemic insults, impaired wall motion is often transient (myocardial stunning) or prolonged (myocardial hibernation). These phenomena occur because of the loss of essential metabolites such as adenosine, which is needed for adenosine triphosphate (ATP)–dependent contraction. Hibernation, a persisting wall-motion abnormality that is curable with revascularization, must be differentiated from permanent, irreversible damage or completed infarct.

Scar tissue and prognosis

Scars involving less than one third of the thickness of the wall, as shown on contrast-enhanced MRI, likely correspond to a recovery of myocardial function, whereas with scars measuring more than one third the thickness of the wall, the potential for recovery with therapy is limited (except in cases involving research cell therapies or surgical scar revision). Other findings associated with recovery are activity on 2-[Fluorine 18]-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) scanning and a monophasic or biphasic contractile response to dobutamine infusion, caused by the induction of ischemia.

As recommended by the most recent American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the management of unstable angina/NSTEMI, last updated in 2007, patients with symptoms that suggest an acute coronary syndrome should be referred to a facility where a physician can evaluate these symptoms in person and where a 12-lead ECG and cardiac biomarker testing is available (eg, emergency department, acute care facility).

Patients with active symptoms of ACS should be instructed to call emergency services (eg, 911 in the United State) and should be brought in by emergency medical services personnel, not by themselves, family, or friends. Patients should be instructed to come to the emergency department immediately if the suspected ACS symptoms last longer than 20 minutes at rest or are associated with near syncope/syncope or hemodynamic instability.

If nitroglycerin is prescribed to a patient with suspected ACS, the patient should be instructed to take a dose if symptoms arise. If no relief is experienced 5 minutes after the first dose, the patient should contact emergency services. If relief is experienced within 5 minutes of the first nitroglycerin dose, repeated doses can be given every 5 minutes for a maximum of 3 doses total. If by then the symptoms have not yet fully resolved, the patient, a family member, or caregiver should contact emergency services.[28]

Diet plays an important role in the development of coronary artery disease. Educate post–myocardial infarction patients about the role of a low-cholesterol and low-salt diet. Educate patients about the American Heart Association (AHA) dietary guidelines, including a low-fat, low-cholesterol diet. A dietitian should see and evaluate all patients post myocardial infarction prior to their discharge. Additionally, emphasis on exercise training should be made because current evidence demonstrates that cardiac rehabilitation post myocardial infarction results in lower rates of recurrent cardiovascular events.[29]

A Norwegian randomized trial found that aerobic interval training (treadmill) increased peak oxygen uptake more than the usual care rehabilitation (aerobic exercise training) after myocardial infarction.[30]

Following myocardial infarction, educate all patients regarding the critical role of smoking in the development of coronary artery disease. Smoking cessation classes should be offered to help patients avoid smoking after their myocardial infarction.

For patient education resources, see the Heart Health Center and Cholesterol Center, as well as High Cholesterol, Cholesterol Charts (What the Numbers Mean), Lifestyle Cholesterol Management, Chest Pain, Coronary Heart Disease, Heart Attack, Angina Pectoris, Cholesterol-Lowering Medications, and Statins for Cholesterol.

The patient’s history is critical in diagnosing myocardial infarction and sometimes may provide the only clues that lead to the diagnosis in the initial phases of the patient presentation.

Patients with typical myocardial Infarction may have prodromal symptoms of fatigue, chest discomfort, or malaise in the days preceding the event; alternatively, typical STEMI may occur suddenly, without warning.

Myocardial infarction occurs most often in the early morning hours, perhaps partly because of the increase in catecholamine-induced platelet aggregation and increased serum concentrations of plasminogen activator inhibitor-1 (PAI-1) that occur after awakening. In general, the onset is not directly associated with severe exertion. Instead, it is concomitant with exertion. The immediate risk of myocardial infarction increases 6-fold on average and by as much as 30-fold in sedentary people.

Takotsubo cardiomyopathy (TTC) is an acute reversible cardiac condition often triggered by stressful events, which is often confused with acute coronary syndrome. In a 2012 report, TTC events occurred in a circadian pattern with a peak in the afternoon hours, as opposed to the the predilection of STEMI for occurring in the morning hours. This timing is consistent with mechanisms underlying stressful life events that usually trigger TTC.[31]

A high index of suspicion should be maintained for myocardial infarction especially when evaluating women, patients with diabetes, older patients, patients with dementia, patients with a history of heart failure, cocaine users, patients with hypercholesterolemia, and patients with a positive family history for early coronary disease (See Etiology). A positive family history includes any first-degree male relative aged 45 years or younger or any first-degree female relative aged 55 years or younger who experienced a myocardial infarction.

Other symptoms of myocardial infarction include the following:

• Anxiety

• Light-headedness with or without syncope

• Cough

• Nausea with or without vomiting

• Diaphoresis

• Wheezing

The patient may recall only an episode of indigestion as an indication of myocardial infarction (see Physical Examination). In some cases, patients do not recognize chest pain, possibly because they have a stoic outlook, have an unusually high pain threshold, have a disorder that impairs function of the nervous system and that results in a defective anginal warning system (eg, diabetes mellitus), or have obtundation caused by medication or impaired cerebral perfusion. Elderly patients with preexisting altered mental status or dementia may have no recollection of recent symptoms and may have no complaints whatsoever.

For many patients, the first manifestation of coronary artery disease is sudden death likely from malignant ventricular dysrhythmia.

Physical examination findings for myocardial infarction can vary; one patient may be comfortable in bed, with normal examination results, while another may be in severe pain, with significant respiratory distress and a need for ventilatory support.

Patients with ongoing symptoms usually lie quietly in bed and appear pale and diaphoretic. Hypertension may precipitate myocardial infarction, or it may reflect elevated catecholamine levels due to anxiety, pain, or exogenous sympathomimetics. Hypotension may indicate ventricular dysfunction due to ischemia. Hypotension in the setting of myocardial infarction usually indicates a large infarct secondary to either decreased global cardiac contractility or a right ventricular infarct. Acute valvular dysfunction may be present. Valvular dysfunction usually results from infarction that involves the papillary muscle. Mitral regurgitation due to papillary muscle ischemia or necrosis may be present.

The typical chest pain of acute myocardial infarction is intense and unremitting for 30-60 minutes. It is retrosternal and often radiates up to the neck, shoulder, and jaw and down to the ulnar aspect of the left arm. Chest pain is usually described as a substernal pressure sensation that also may be described as squeezing, aching, burning, or even sharp. In some patients, the symptom is epigastric, with a feeling of indigestion or of fullness and gas.

Atypical presentations are common and frequently lead to misdiagnoses. Moreover, any patient may present with atypical symptoms, which are considered the anginal equivalent for that patient. A patient, for example, may present with abdominal discomfort or jaw pain as his or her anginal equivalent. An elderly patient may present with altered mental status. Atypical chest pain is common, especially in elderly patients and patients with diabetes. A low threshold should be maintained when evaluating high- and moderate-risk patients, as their anginal equivalents may mimic other presentations. Women tend to present more commonly with atypical symptoms such as sharp pain, fatigue, weakness, and other nonspecific complaints.

Diaphoresis, weakness, a sense of impending doom, profound restlessness, confusion, presyncope, hiccupping (which presumably reflects irritation of the phrenic nerve or diaphragm), nausea and vomiting, and palpitations may be present. (Nausea and/or abdominal pain often are present in infarcts involving the inferior or posterior wall.)

Decreased systolic ventricular performance may lead to impaired perfusion of vital organs and reflex-mediated compensatory responses, such as restlessness, impaired mentation, pallor, peripheral vasoconstriction and sweating, tachycardia, and prerenal failure.

By contrast, impaired left ventricular diastolic function leads to pulmonary vascular congestion with shortness of breath and tachypnea and, eventually, pulmonary edema with orthopnea. Shortness of breath may be the patient's anginal equivalent or a symptom of heart failure. In an elderly person or a patient with diabetes, shortness of breath may be the only complaint.

In patients with acute inferior-wall myocardial infarction with right ventricular involvement, distention of neck veins is commonly described as a sign of failure of the RV. (Central venous pressure is most properly estimated independently of venous distension on the basis of the height of the meniscus of venous pulsation above the mid atrium.) Impaired right ventricular diastolic function also leads to systemic venous hypertension, edema, and hepatomegaly with abdominojugular reflux, which may result in saline-response underfilling of the LV and a concomitant reduction in cardiac output.

Elderly patients and those with diabetes may have particularly subtle presentations and may complain of fatigue, syncope, or weakness. The elderly may also present with only altered mental status.

As many as half of myocardial infarctions are clinically silent in that they do not cause the classic symptoms described above and consequently go unrecognized by the patient. Myocardial infarction is clinically silent in as many as 25% of elderly patients, a population in whom 50% of myocardial infarctions occur; in such patients, the diagnosis is often established only retrospectively, by applying electrocardiographic criteria or by scanning the patients using 2-dimensional (2D) echocardiography or magnetic resonance imaging (MRI).

On clinical evaluation, ventricular aneurysms may be recognized late, with symptoms and signs of heart failure, recurrent ventricular arrhythmia, or recurrent embolization.

Vital signs

The patient's heart rate is often increased secondary to sympathoadrenal discharge. The pulse may be irregular because of ventricular ectopy, an accelerated idioventricular rhythm, ventricular tachycardia, atrial fibrillation or flutter, or other supraventricular arrhythmias. Bradyarrhythmias may be present; bradyarrhythmias may be attributable to impaired function of the sinus node. An AV nodal block or infranodal block may be evident.

In general, the patient's blood pressure is initially elevated because of peripheral arterial vasoconstriction resulting from an adrenergic response to pain and ventricular dysfunction. However, with right ventricular myocardial infarction or severe left ventricular dysfunction, hypotension is seen.

The respiratory rate may be increased in response to pulmonary congestion or anxiety.

Coughing, wheezing, and the production of frothy sputum may occur.

Fever is usually present within 24-48 hours, with the temperature curve generally parallel to the time course of elevations of creatine kinase (CK) levels in the blood. Body temperature may occasionally exceed 102°F.

Funduscopic examination

Manifestations of atherosclerotic vascular disease include copper wiring, or narrowing, of arterioles. Hypertension may manifest with arteriovenous nicking, which is a pinching of the veins by small arteries where they cross. Extreme hypertension may cause cupping or loss of the margins of the optical disk. Antecedent long-standing hypertension may be reflected by arterial narrowing and hemorrhages.

Arterial pulsations

Arterial pulsations may exhibit pulsus alternans, which reflects impaired left ventricular function and is characterized by strong and weak alternating pulse waves (the variation in systolic pressure is >20 mm Hg). Carotid pulsation may be thin (pulsus parvus) because of decreased amplitude and length of the pulse secondary to decreased stroke volume.

Pulsus bisferiens consists of 2 systolic peaks; it may be palpated in association with hypertrophic obstructive cardiomyopathy (HOCM) or mixed aortic stenosis and regurgitation. A dicrotic pulse is encountered in cases involving hypovolemic shock, severe heart failure, or cardiac tamponade. It manifests as a double pulse, produced by a combination of the systolic wave followed by an exaggerated dicrotic (diastolic) wave.

A bigeminal pulse is observed in the presence of ectopic beats or Wenckebach heart block; it is characterized by regular coupling of 2 beats with the interval between a pair of beats greater than that between the coupled beats themselves.

Pulsus paradoxus is defined as a decline in systolic blood pressure of 10 mm Hg or more on inspiration; it is seen in cases involving cardiac tamponade, constrictive pericarditis, restrictive cardiomyopathy, hypotensive shock, severe chronic lung disease, or pulmonary embolism.

In patients with associated aortic regurgitation, a pulse with sharp descent, or a water-hammer pulse, may be observed.

Venous pulsations

Jugular venous distention may accompany right ventricular myocardial infarction or right ventricular failure secondary to profound left ventricular dysfunction and pulmonary hypertension. It may also be elevated as a result of an increase in right atrial pressure in patients with heart failure, decreased right ventricular compliance, pericardial disease, fluid overload, or tricuspid or superior vena cava obstruction. The Kussmaul sign, characterized by a paradoxical increase in jugular venous pressure during inspiration, may occur in patients with constrictive pericarditis, congestive HF (CHF), or tricuspid stenosis.

Chest

Rales or wheezes may be auscultated; these occur secondary to pulmonary venous hypertension, which is associated with extensive acute left ventricular myocardial infarction. Unilateral or bilateral pleural effusions may produce egophony at the lung bases. On chest radiographs, they are evidenced by blunted costophrenic angles; on MRI, they are evidenced by dependent fluid signal intensity; on echocardiography, they are evidenced by echolucent zones adjacent to the heart.

Heart

On palpation, lateral displacement of the apical impulse, dyskinesis, a palpable S4 gallop, and a soft S1 sound may be found. These indicate diminished contractility of the compromised LV.

Paradoxical splitting of S2 may reflect the presence of left bundle-branch block or prolongation of the preejection period with delayed closure of the aortic valve, despite decreased stroke volume.

Increased S4 and S3 gallops may suggest increased LV stiffness; they represent the rapid filling phase (S3) or atrial contraction (S4).

A mitral regurgitation murmur (typically holosystolic near the apex) indicates papillary muscle dysfunction or rupture or mitral annular dilatation; it may be audible even when cardiac output is substantially decreased.

A holosystolic systolic murmur that radiates to the midsternal border and not to the back, possibly with a palpable thrill, suggests a ventricular septal rupture; such a rupture may occur as a complication in some patients with full-thickness (or Q-wave) myocardial infarctions. With resistive flow and an enlarged pressure difference, the ventricular septal defect murmur becomes harsher, louder, and higher in pitch than before.

A pericardial friction rub may be audible as a to-and-fro rasping sound with 1-3 components; it is produced through sliding contact of inflammation-roughened surfaces.

Neck vein and pulse patterns, splitting of S2, or ECG findings may suggest premature ventricular beats, brief runs of ventricular tachycardia, accelerated idioventricular rhythm, atrial flutter or atrial fibrillation, or conduction delays.

Abdomen

Patients frequently develop tricuspid incompetence; hepatojugular reflux may be elicited even when hepatomegaly is not marked.

Extremities

Peripheral cyanosis, edema, pallor, diminished pulse volume, delayed rise, and delayed capillary refill may indicate vasoconstriction, diminished cardiac output, and right ventricular dysfunction or failure. Pulse and neck-vein patterns may reveal other associated abnormalities, as previously discussed. Dependent edema may be graded 0-4 by assessing the depth of persistent pitting after thumb pressure is applied to the patient's inner shin for more than 10 seconds or by evaluating the lower back if the patient has had his or her legs elevated.

The objectives of laboratory testing and imaging include the following:

• To determine the presence or absence of myocardial infarction for diagnosis and differential diagnosis (point–of-care testing and testing in central laboratory of cardiac biomarkers)

• To characterize the locus, nature (STEMI or NSTEMI), and extent of myocardial infarction (ie, to estimate infarct size)

• To detect recurrent ischemia or myocardial infarction (extension of myocardial infarction)

• To detect early and late complications of myocardial infarction

• To estimate the patient's prognosis

Laboratory evaluation is particularly helpful in the presence of comorbid conditions that may affect the patient's prognosis and influence his or her care. Such comorbidities include the following:

• Diabetes

• Renal or hepatic failure

• Anemia

• Bleeding disorders

• Respiratory failure

Cardiac imaging

The role of imaging in ACSs is broad, but the procedures are primarily used to confirm or rule out coronary disease. Furthermore, it may help define the anatomy and degree of myocardial perfusion abnormalities. In lower-risk individuals in whom ACS is suspected and who do not have serial ECG changes or positive serial cardiac biomarker findings, the ACC/AHA guidelines recommend some form of stress testing to help confirm the diagnosis and guide therapy.[28]

For individuals with highly probable or confirmed ACS, consultation with a cardiologist is carried out so that coronary angiography can be performed; this procedure can be used to definitively diagnose or rule out coronary artery disease. Based on the angiographic result and patient comorbidities, subsequent treatment recommendations can be made, which may include medical therapy, percutaneous coronary intervention (PCI), or coronary artery bypass grafting (CABG) surgery.

High-risk coronary plaque may independently predict ACS in patients with acute chest pain in the emergency department (ED).[32, 33, 34] Coronary computed-tomography angiography (CCTA) may detect high-risk coronary plaque features in patients with acute chest pain and a negative initial ECG or troponin test in the ED; such plaques may predict which patients are at higher risk of imminent ACS (MI or unstable angina).[32, 33]

In addition, high-risk plaque appears to be an independent risk factor for an increased risk of ACS. The data were derived from 472 patients in the CCTA arm of the Rule Out Myocardial Infarction With Computer Assisted Tomography II (ROMICAT II) study which showed that, after adjustment for stenosis (>50%) and other cardiovascular risk factors, patients with high-risk plaques were significantly more likely to have ACS during their index hospitalization.[32, 33]

In a separate study, automated software that quantified plaque features in 56 coronary lesions improved the ability to predict lesion-specific ischemia.[33, 34] The investigators believe that this technique has the potential to noninvasively identify hemodynamically significant coronary lesions.[34]

The American College of Cardiology/American Heart Association (ACC/AHA) guidelines on unstable angina/NSTEMI recommend that in patients with suspected myocardial infarction, cardiac biomarkers should be measured at presentation. The guidelines recommend a total turnaround time of less than 1 hour and preferably less than 30 minutes for the cardiac biomarker measurements.

Several studies have shown that implementation of point-of-care testing (POCT) for cardiac biomarkers may improve early diagnosis as well as decrease patient length of stay.[35] Additional studies are needed to determine the relative analytic performance of different POCT assays for troponins, creatine phosphokinase–myocardial band (CPK-MB) and myoglobin alone or in combination in the current state of analytical technologies.

If initial markers are negative and have been measured within 6 hours of symptom onset, the biomarkers should be remeasured within 8-12 hours after symptom onset. Remeasuring cardiac enzyme levels at regular intervals for the first 24 hours is a reasonable approach to improving the sensitivity of detection of myocardial necrosis, and the degree of positivity can be important for prognostication. Note the graph below.[28]

In addition, biomarkers alone or as part of accelerated diagnostic protocols (ADP) can reduce the number of patients with a missed diagnosis of NSTEMI who are at increased risk of major adverse cardiac events. Furthermore, such approaches can facilitate early discharge from the ED in patients who a have a low short-term risk of a major cardiac event as reported in The Asia-Pacific Evaluation of Chest Pain Trial (ASPECT).[36]

Troponin is a contractile protein that normally is not found in serum. It is released only when myocardial necrosis occurs.

Troponin levels are now considered to be the criterion standard for defining and diagnosing myocardial infarction, according to the American College of Cardiology (ACC)/American Heart Association (AHA) consensus statement on myocardial infarction.[37, 38]

Positive troponin levels are considered virtually diagnostic of myocardial infarction, according to a revised version of the ACC/AHA consensus statement, as they are without equal in combined specificity and sensitivity in this diagnosis. Reichlan et al suggest that absolute changes in troponin levels have a significantly higher diagnostic accuracy for acute myocardial infarction than relative changes.[39]

Serum levels increase within 3-12 hours from the onset of chest pain, peak at 24-48 hours, and return to baseline over 5-14 days.

Improved cardiac troponin assays offer even greater diagnostic accuracy than the standard assays do, according to a study by Reichlin et al. This is especially true for the early diagnosis of acute myocardial infarction, particularly in patients with a recent onset of chest pain, according to the investigators.[40]

Keller et al suggest that among patients with suspected acute coronary syndrome, highly sensitive troponin I assay (hsTnI) or contemporary troponin I assay (cTnI) determination 3 hours after admission for chest pain may facilitate early rule-out of acute myocardial infarction. A serial change in hsTnI or cTnI levels from admission (using the 99th percentile diagnostic cutoff value) to 3 hours postadmission may aid in early diagnosis of acute myocardial infarction.[41]

According to Hubbard et al, in patients without heart failure with marginally increased troponin levels, a low BNP level (BNP ≤80 pg/mL) cannot identify patients at low-risk for 30-day acute MI or death.[42]

MI is a strong trigger of N-terminal pro-B-type natriuretic peptide (NT-proBNP) release, and checking these levels may improve the early diagnosis and risk stratification of patients with suspected acute MI.[43]

For more information, see Use of Cardiac Markers in the Emergency Department.

The 3 CK isoenzymes are as follows:

• CK with muscle subunits (CK-MM), which is found mainly in skeletal muscle

• CK with brain subunits (CK-BB), which is found predominantly in the brain

• CK-MB, which is found mainly in the heart

Serial measurements of CK-MB isoenzyme levels were previously the standard criterion for the diagnosis of myocardial infarction. CK-MB levels increase within 3-12 hours of the onset of chest pain, reach peak values within 24 hours, and return to baseline after 48-72 hours. levels peak earlier (wash out) if reperfusion occurs. Sensitivity is approximately 95%, with high specificity. However, sensitivity and specificity are not as high as they are for troponin levels, and, as mentioned above, the trend has favored using troponins for the diagnosis of myocardial infarction.

Myoglobin, a low-molecular-weight heme protein found in cardiac and skeletal muscle, is released more rapidly from infarcted myocardium than is troponin. Urine myoglobin levels rise within 1-4 hours from the onset of chest pain. Myoglobin levels are highly sensitive but not specific; they may be useful within the context of other studies and in the early detection of myocardial infarction in the emergency department (ED).

Complete blood cell count

Obtain a complete blood cell (CBC) count if myocardial infarction is suspected in order to rule out anemia as a cause of decreased oxygen supply and prior to giving thrombolytic agents. Leukocytosis is also common, but not universal, in the setting of acute myocardial infarction.

A platelet count is necessary if a IIb/IIIa agent is considered; furthermore, the patient's white blood cell (WBC) count may be modestly elevated in the setting of myocardial infarction, signifying an acute inflammatory state. The platelet count may become dangerously low after the use of heparin because of heparin-induced thrombocytopenia (HIT). The leukocyte count may be normal initially, but it generally increases within 2 hours and peaks in 2-4 days, with predominance of polymorphonuclear leukocytes and a shift to the left. Elevations generally persist for 1-2 weeks.

Chemistry profile

In the setting of myocardial infarction, closely monitor potassium and magnesium levels. The creatinine level is also needed, prior to initiating treatment with an ACE inhibitor.

The erythrocyte sedimentation rate (ESR) rises above reference range values within 3 days and may remain elevated for weeks.

The serum lactate dehydrogenase (LDH) level rises above the reference range within 24 hours of myocardial infarction, reaches a peak within 3-6 days, and returns to the baseline within 8-12 days.

Blood oxygenation should be checked and repeatedly corrected if any clinical findings suggest hypoxemia; hypoxemia may result from pulmonary congestion, atelectasis, or ventilatory impairment secondary to complications of myocardial infarction or excessive sedation or analgesia. Fingertip oximetry may be adequate in the absence of carbon dioxide retention and may obviate puncture to assess arterial blood gases (ABGs). Such puncturing may lead to bleeding in patients being treated with thrombolytic drugs. However, normal oxygen saturation does not exclude impending respiratory failure.

Lipid profile

This may be helpful if obtained upon presentation, because levels can change after 12-24 hours of an acute illness.

C-reactive protein and other inflammation markers

Consider measuring C-reactive protein (CRP) levels and other inflammation markers upon presentation if an ACS is suspected.

As recommended by the most recent ACC/AHA guidelines for the management of unstable angina/NSTEMI, last updated in 2007, patients with active ongoing symptoms suggestive of an acute coronary syndrome should have early risk stratification by checking cardiac enzyme levels and undergoing a 12-lead ECG within 10 minutes of presentation of the emergency department. For patients with ongoing symptoms, serial ECGs should be performed to look for dynamic changes in the ST segment.[28]

The ECG is the most important tool in the initial evaluation and triage of patients in whom an ACS is suspected. It is confirmatory of the diagnosis in approximately 80% of cases. The electrocardiographic evidence of myocardial infarction is seen in the images below.

Obtain an ECG immediately if myocardial infarction is considered or suspected. In patients with inferior myocardial infarction, record a right-sided ECG to rule out right ventricular infarct. Qualified personnel should review the ECG as soon as possible.

Electrocardiography should be performed serially upon presentation to evaluate progression and assess changes with and without pain. Obtain daily serial ECGs for the first 2-3 days and additionally as needed.

Because the symptoms of acute myocardial infarction can be subtle or protean, electrocardiography should be performed on any patient who is older than age 45 years and is experiencing any form of thoracoabdominal discomfort, including new epigastric pain or nausea.

In younger patients, an ECG should be considered when suggestive symptoms are present or when risk factors exist for early coronary artery disease. Younger patients are disproportionately represented in missed cases. An ECG is a rapid, low-risk, relatively low-cost measure.

Electrocardiographic abnormalities

The diagnosis may be established with certainty when typical ST-segment elevation persists for hours and is followed by inversion of T waves during the first few days and by the development of Q waves. However, initial ST depression or T-wave inversion associated with myocardial infarction is difficult to differentiate from that seen in the presence of ischemia without myocardial infarction or in unrelated conditions.

ST-segment depression followed by T-wave inversion without the evolution of Q waves may result from non–Q-wave myocardial infarction or from subendocardial ischemia without myocardial infarction. True posterior-wall myocardial infarctions may cause precordial ST depression, inverted and hyperacute T waves, or both. ST-segment elevation and upright hyperacute T waves may be evident with the use of right-sided chest leads.

High probability of myocardial infarction is indicated either by ST-segment elevation greater than 1 mm in 2 anatomically contiguous leads or by the presence of new Q waves. Results that indicate intermediate probability of myocardial infarction are ST-segment depression, T-wave inversion, and other nonspecific ST-T wave abnormalities. Results that indicate low probability of myocardial infarction are normal findings on ECGs; however, normal or nonspecific findings on ECGs do not exclude the possibility of myocardial infarction.

Localization based on distribution of electrocardiographic abnormalities is as follows:

• Inferior wall - II, III, aVF (See the image below.)

  The right-sided leads indicate ST-segment elevations in RV<inf>3</inf> to RV<inf>5</inf>, which are consistent with a right ventricular infarct.

• Lateral wall - I, aVL, V4 through V6

• Anteroseptal - V1 through V3

• Anterolateral - V1 through V6

• Right ventricular - RV4, RV5

• Posterior wall - R/S ratio greater than 1 in V1 and V2; T-wave changes (ie, upright) in V1, V8, and V9

Right ventricular myocardial infarction commonly is manifested by ST-segment elevation or Q waves detectable in right-sided precordial leads. The appearance of abnormalities in a large number of ECG leads often indicates extensive injury or concomitant pericarditis.

Anterior and anterolateral myocardial infarctions tend to involve more left ventricular myocardium than do inferior or true posterior myocardial infarctions. Hyperacute (symmetrical and often but not necessarily pointed) T waves are frequently an early sign of myocardial infarction at any locus. The characteristic electrocardiographic changes may be seen in conditions other than acute myocardial infarction. For example, patients with previous myocardial infarction and left ventricular aneurysm may have persistent ST elevation resulting from dyskinetic wall motion, rather than from acute ischemic injury. ST-segment changes may also be the result of misplaced precordial leads, hypothermia (elevated J point or Osborne waves), or hypothyroidism.

False q waves may be seen in septal leads in hypertrophic-obstructive cardiomyopathy (HOCM). They may also result from cardiac rotation.

Substantial T-wave inversion may be seen in some forms of left ventricular hypertrophy with secondary changes. The Q-T segment may be prolonged because of ischemia or hypomagnesemia. Saddleback ST-segment elevation (Brugada epsilon waves) may be seen in leads V1 -V3 in patients with a congenital predisposition to life-threatening arrhythmias. This elevation may be confused with that observed in acute anterior myocardial infarction. Brugada electrocardiographic changes may be seen during the administration of procainamide or a beta-blocker in patients whose ECG was previously normal. Brain injuries also may trigger changes in T waves.

Convex ST-segment elevation with upright or inverted T waves is generally indicative of myocardial infarction in the appropriate clinical setting. ST depression and T-wave changes may also indicate evolution of NSTEMI.

Unfortunately, in a series of missed myocardial infarction, the failure to recognize ischemic changes is frequent. The inferior leads, in particular, must be scrutinized carefully for any evidence of ST-segment elevation by using a straight edge across the T-P segments.

Another common error is to recognize ischemic changes and then discharge the patient without definitively proving that the changes were preexistent.

Nonischemic causes of ST-segment elevation include left ventricular hypertrophy, pericarditis, ventricular-paced rhythms, hypothermia, hyperkalemia, and left ventricular aneurysm. Nonischemic causes may lead to overtreatment.

Patients with a permanent pacemaker in place may confound recognition of STEMI by 12-lead ECG due to the presence of paced ventricular contractions.

The roles and appropriateness of imaging in acute coronary syndromes (ACSs) are broad but primarily are used to confirm or rule out coronary disease. Furthermore, it may help define the anatomy and degree of myocardial perfusion abnormalities.

In lower-risk individuals in whom ACS is suspected, serial ECG changes are not present, and serial cardiac biomarkers are negative, the ACC/AHA guidelines recommend for some form of stress testing to help confirm diagnosis and guide therapy.[28] In individuals with highly probable or confirmed ACS, consultation to a cardiologist is made to perform a coronary angiogram to definitively diagnose or rule out coronary artery disease. Based on the angiographic result and patient comorbidities, subsequent treatment recommendations can be made: medical therapy, percutaneous coronary intervention (PCI), or coronary artery bypass grafting (CABG) surgery.

High-risk coronary plaque may independently predict ACS in patients with acute chest pain in the emergency department (ED).[32, 33, 34] Coronary computed-tomography angiography (CCTA) may detect high-risk coronary plaque features in patients with acute chest pain and a negative initial ECG or troponin test in the ED; such plaques may predict which patients are at higher risk of imminent ACS (MI or unstable angina).[32, 33]

In addition, high-risk plaque appears to be an independent risk factor for an increased risk of ACS. The data were derived from 472 patients in the CCTA arm of the Rule Out Myocardial Infarction With Computer Assisted Tomography II (ROMICAT II) study which showed that, after adjustment for stenosis (>50%) and other cardiovascular risk factors, patients with high-risk plaques were significantly more likely to have ACS during their index hospitalization.[32, 33]

In a separate study, automated software that quantified plaque features in 56 coronary lesions improved the ability to predict lesion-specific ischemia.[33, 34] The investigators believe that this technique has the potential to noninvasively identify hemodynamically significant coronary lesions.[34]

Please see Acute Myocardial Infarct Imaging for more detailed information.

Stress echocardiography

Stress echocardiography can be used to rule out myocardial ischemia in patients who come to the emergency department with chest pain, according to a retrospective study of 474 unselected consecutive patients who presented with spontaneous chest pain, a nondiagnostic ECG, and negative cardiac enzymes at baseline and after 6 and 12 hours.[44, 45]

Exercise stress echocardiography was performed in 270 patients, showing inducible ischemia in 41; dobutamine stress echocardiography was performed in 218, showing inducible ischemia in 72. Of the 113 patients with inducible ischemia, 98 underwent angiography, which revealed significant coronary artery disease in 78.[45] The 2 types of stress echocardiography yielded statistically similar sensitivities (88% and 90%, respectively), positive predictive values (90% and 70%), and negative predictive values (98% and 95%); exercise stress echocardiography was significantly more specific (98% vs 83%).

Coronary artery calcium scoring is an emerging technique that appears to add some predictive value in identifying patients at low risk for coronary artery disease. However, in high-risk patients or in those who have established coronary artery disease, the test does not appear to be helpful at this time.[37, 38]

Morbidity and mortality from myocardial infarction are significantly reduced if patients and bystanders recognize symptoms early, activate the emergency medical service (EMS) system, and thereby shorten the time to definitive treatment. Trained prehospital personnel can provide life-saving interventions if the patient develops cardiac arrest.

The key to improved survival is the availability of early defibrillation. Approximately 1 in every 300 patients with chest pain transported to the ED by private vehicle goes into cardiac arrest en route. Several studies have confirmed that patients with STEMI usually do not call 911; in one study, only 23% of patients with a confirmed coronary event used EMS.

The first goal for healthcare professionals is to diagnose in a very rapid manner whether the patient is having an STEMI or NSTEMI because therapy differs between the 2 types of myocardial infarction. Particular considerations and differences involve the urgency of therapy and degree of evidence regarding different pharmacological options.

As a general rule, initial therapy for acute myocardial infarction is directed toward restoration of perfusion as soon as possible to salvage as much of the jeopardized myocardium as possible. This may be accomplished through medical or mechanical means, such as PCI or CABG.

Further treatment is based on the following:

• Restoration of the balance between the oxygen supply and demand to prevent further ischemia

• Pain relief

• Prevention and treatment of any complications that may arise

Coronary collateral circulation

The coronary collateral circulation is an important factor in terms of the amount of damage to the myocardium that results from coronary occlusion. Well-developed collaterals may greatly limit or even completely eliminate myocardial infarction despite complete occlusion of a coronary artery.

Reports vary as to the number of patients who have collaterals at the time of a myocardial infarction; many patients develop collaterals in the hours and days after an occlusion occurs.[46] When the patient is at rest, blood flow through collaterals is normal, a fact that accounts for the absence of resting ischemia. However, blood flow through collaterals does not increase with exercise; this inability accounts for the occurrence of ischemia during periods of stress.[47]

All patients being transported for chest pain should be managed as if the pain were ischemic in origin, unless clear evidence to the contrary is established. If available, an advanced life support (ALS) unit should transport patients with hemodynamic instability or respiratory difficulty.

Prehospital notification by Emergency Medical Services (EMS) personnel should alert ED staff to the possibility of a patient with myocardial infarction. EMS personnel should receive online medical advice for a patient with high-risk presentation.

The AHA protocol can be adopted for use by prehospital emergency personnel. This protocol recommends empiric treatment of patients with suspected STEMI with morphine, oxygen, nitroglycerin, and aspirin.

Specific prehospital care includes the following:

• Intravenous access, supplemental oxygen, pulse oximetry

• Immediate administration of aspirin en route

• Nitroglycerin for active chest pain, given sublingually or by spray

• Telemetry and prehospital ECG, if available

Most deaths caused by myocardial infarction occur early and are attributable to primary ventricular fibrillation (VF). Therefore, initial objectives are immediate electrocardiographic monitoring; electric cardioversion of VF, should it occur; and rapid transfer of the patient to facilitate prompt coronary recanalization. The effectiveness of rapid response by rescuers (eg, police and firefighters) trained in defibrillation have been conclusively documented in community-based systems in Belfast, Ireland; Columbus, Ohio; Los Angeles, California; and Seattle, Washington.

Approximately 65% of deaths caused by myocardial infarction occur in the first hour. More than 60% of these deaths (ie, 39% of patients who would otherwise die) may be prevented with defibrillation by a bystander or a first-responding rescuer.

Additional objectives of prehospital care by paramedical and emergency personnel include adequate analgesia (generally achieved with morphine); pharmacologic reduction of excessive sympathoadrenal and vagal stimulation; treatment of hemodynamically significant or symptomatic ventricular arrhythmias (generally with lidocaine); and support of cardiac output, systemic blood pressure, and respiration.

The AHA published a statement on integrating prehospital ECGs into care for patients with ACS (see AHA Publishes Statement on Integrating Prehospital ECGs Into Care for ACS Patients). Prehospital integration of ECG interpretation has been shown to decrease "door to balloon time," to allow paramedics to bypass non-PCI hospitals in favor of better-equipped facilities and to expedite care by allowing an emergency physician to activate the catheterization laboratory before patient arrival.

Prehospital administration of tissue-type plasminogen activator (t-PA), aspirin, and heparin may be given to patients with bona fide myocardial infarction by paramedics, as guided by electrocardiographic findings, within 90 minutes of the onset of symptoms. This treatment improves outcomes, as compared with thrombolysis begun after the patient arrives at the hospital.

Atropine, 0.5 mg given intravenously at 5-minute intervals to a maximum of 2-4 mg, is useful to counteract excessive vagal tone that often underlies bradyarrhythmias and hypotension. If bradycardia persists, transthoracic pacing may be life saving.

Timely reperfusion therapy has shown that the long-term mortality rate in patients with STEMI is 15.4% when the system delay (time from first contact with health care system to the initiation of reperfusion therapy) is 60 minutes or less. The long-term mortality doubles to a rate of 30.8% when the system delay is more than 180 minutes.[48]

In experimental models of MI, erythropoietin reduces infarct size and improves left ventricular (LV) function. However, the Reduction of Infarct Expansion and Ventricular Remodeling With Erythropoietin After Large Myocardial Infarction (REVEAL) trial evaluated the safety and efficacy of a single intravenous bolus of epoetin alfa in patients with STEMI who had successful reperfusion with primary or rescue PCI.[49] A single intravenous bolus of epoetin alfa within 4 hours of PCI did not reduce infarct size and was associated with higher rates of adverse cardiovascular events.

For purposes of determining appropriate emergency treatment, viewing myocardial infarction as part of a spectrum of coronary syndromes is helpful; this spectrum includes the following:

• STEMI

• NSTEMI

• Unstable angina

Treatment is aimed at the following:

• Restoration of the balance between the oxygen supply and demand to prevent further ischemia

• Pain relief

• Prevention and treatment of complications

Treatment in the ED begins with focused cardiovascular history–taking and physical examination, the establishment of intravenous (IV) access, the use of 12-lead ECG (see the image below), and continuous rhythm monitoring. All patients with suspected myocardial infarction should be given chewable aspirin, 160-325 mg, unless they have a documented allergy to aspirin.

Pulse oximetry should be performed, and appropriate supplemental oxygen should be given (maintain oxygen saturation >90%) to prevent hypoxemia. High concentrations may be counterproductive because of vasoconstriction and the lack of augmented myocardial oxygen delivery in normoxemic patients.

Note that supplemental oxygen may harm nonhypoxic patients with STEMI, increasing the risk of myocardial injury, recurrent myocardial infarction, and major cardiac arrhythmia, according to results of the randomized, controlled, multicenter Air Versus Oxygen in ST-Elevation Myocardial Infarction (AVOID) study.[50] The trial involved patients with STEMI who had normal oxygen levels (ie, oxygen saturation levels of more than 94%), with the patients randomized into two groups: those who received supplemental oxygen (218 patients) and those who were given no supplemental oxygen (223 patients) unless their oxygen saturation level fell below 94%.[50]

A 25% rise in creatine kinase, suggesting increased myocardial injury, was observed at the primary endpoint in the supplemental oxygen group. Primary endpoint results for troponin I, however, did not differ significantly between the two groups. It was also found that both groups had a similar mortality rate (although the study did not have enough power to examine major adverse cardiac events). However, the rates of MI recurrence and significant arrhythmia were significantly higher in the supplemental oxygen group, but these differences were no longer significant at 6 months.[50]

A chest radiograph should be obtained soon after arrival, to screen for alternative causes of chest pain and to identify possible contraindications to thrombolysis (eg, aortic dissection).

Initial stabilization of patients with suspected myocardial infarction and ongoing acute chest pain should include administration of sublingual nitroglycerin; if pain persists, 2 additional doses of nitroglycerin may be administered at 5-minute intervals. Patients should be free of contraindications, such as hypotension (systolic blood pressure < 90 mm Hg), bradycardia, tachycardia, or findings suggestive of right ventricle [RV] infarction.

Refractory or severe pain should be treated symptomatically with IV morphine, meperidine, or pentazocine. Doses of morphine, 4-8 mg IV, may be repeated every 5-15 minutes with relative impunity until the pain is relieved or toxicity is manifested by hypotension, vomiting, or depressed respiration. Should toxicity occur, a morphine antagonist, such as naloxone, may reverse it. The patient's blood pressure and pulse must be monitored; the systolic blood pressure must be maintained above 100 mm Hg and, optimally, below 140 mm Hg.

Relative hypotension may be treated by elevating the lower extremities or by giving fluids, except in patients with concomitant pulmonary congestion, in whom treatment for cardiogenic shock may be required. Atropine, in doses similar to those given in the prehospital phase, may increase blood pressure if hypotension reflects bradycardia or excess vagal tone.

Some EDs practice ambulance diversion, wherein the ED is temporarily closed to ambulance traffic.[51] This practice has been associated with increased 30-day, 90-day, 9-month, and 1-year mortality among patients using Medicare who experienced acute myocardial infarction. Although confined to California, this study by Shen et al shows the importance between ED care and the survival of patients experiencing acute myocardial infarction.

Treatment of patients with STEMI

The initial focus in the ED should be on identifying patients with STEMI. An ECG should be performed and shown to an experienced emergency medicine physician within 10 minutes of ED arrival. The 2013 guidelines from the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) for the management of patients with STEMI recommend ECGs be done in the field by ambulance personnel to facilitate more rapid triage and quicker treatment.[52, 53]

If STEMI is present, the decision as to whether the patient will be treated with thrombolysis or primary PCI should be made within the next 10 minutes. Treatment options include the immediate start of IV thrombolysis in the ED or the immediate transfer of the patient to the cardiac catheterization laboratory for primary percutaneous transluminal coronary angioplasty (PTCA).[2, 3] The goal for patients with STEMI should be to achieve a door-to-drug time of within 30 minutes and a door-to-balloon time of within 90 minutes.

In patients with STEMI who are to be treated with primary PCI, delays in administering the procedure are associated with higher mortality in these patients, according to a study by Rathore et al.[54] In a prospective cohort study of 43,801 patients enrolled in the American College of Cardiology National Cardiovascular Data Registry, 2005-2006, longer door-to-balloon times were associated with a higher adjusted risk of in-hospital mortality, in a continuous, nonlinear fashion (30 min = 3%, 60 min = 3.5%, 90 min = 4.3%, 120 min = 5.6%, 150 min = 7%, 180 min = 8.4%). A reduction in door-to-balloon time from 90 minutes to 60 minutes was associated with 0.8% lower mortality, and a reduction from 60 minutes to 30 minutes was associated with a 0.5% lower mortality.

Delays in the administration of thrombolysis often occur because of the following factors:

• Delay in obtaining an ECG

• Interpretation

• Lack of immediate availability of thrombolytic agents

• Outdated protocols requiring cardiology consultation before thrombolytic treatment

The AHA recommends the initiation of beta-blockers to all patients with STEMI (unless beta-blockers are contraindicated). Sinert et al reviewed records from 1966 to August 2009 to determine the efficacy of treating STEMI patients with beta-blockers within the first 24 hours. They found a single randomized trial that met inclusion criteria. This trial demonstrated that beta-blocker treatment within 24 hours in patients presenting with STEMI followed by standardized care on day 2 or 3 did not reduce mortality or reinfarction when compared with placebo or no immediate treatment followed by standardized care.[55]

A separate study by Brinkman et al also suggests that although a rationale for the use of beta-blockers prior to surgery has been reported, the use of these drugs should be considered on an individual basis. Because no differences in mortality or morbidity were found, the findings did not support preoperative beta-blockade as a useful quality indicator for coronary artery bypass graft surgery.[56]

In a placebo-controlled, multicenter trial of 240 STEMI (ST-segment elevation myocardial infarction) patients treated with percutaneous coronary intervention (PCI) and thrombus aspiration, the additional intracoronary administration of adenosine, but not nitroprusside, significantly improved microvascular obstruction (MVO). ST-segment resolution >70% on surface electrocardiogram at 90 minutes after PCI occurred in 71% of patients treated with adenosine, 54% of those treated with nitroprusside, and 51% of those who received saline. Angiographic MVO occurred in 18% of the adenosine group, 24% of the nitroprusside group, and 30% of the placebo group. Major adverse cardiac events were observed in 10%, 14%, and 20% of these groups, respectively.[57]

Treatment of patients with NSTEMI

If STEMI is not present, then the workup should proceed looking for unstable angina or NSTEMI and for alternative diagnoses. Confirmation of the diagnosis of NSTEMI requires waiting for the results of cardiac markers.

Point-of-care (POC) assays are common in the ED setting but have lower negative predictive values compared with laboratory assays. The current POC cardiac troponin I (cTnI) assays are less sensitive for outcome prediction among patients with myocardial injury.[58] Clinical judgment and decision-making for the patient with suspected acute coronary syndrome (ACS) should not rely solely on POC assay results. If a clinical suspicion of myocardial infarction remains despite negative cTnI results with the POC assays, those results should be complemented by results from more sensitive laboratory assays.

In the case of unstable angina, diagnosis may await further diagnostic studies, such as coronary angiography or imaging studies, to confirm the diagnosis and to distinguish it from noncoronary causes of chest pain. Although patients presenting with no ST-segment elevation are not candidates for immediate treatment with thrombolytic agents, they should receive anti-ischemic therapy and may be candidates for PCI urgently or during admission.

Low-risk patients

Low-risk patients without obvious ischemia should be observed and monitored in either a step-down care unit or an intermediate care unit to evaluate or observe for chest pain.

Concordance of ED management of AMI

A study by Tsai et al determined that overall ED concordance with ACC/AHA guideline recommendations for management of AMI is low to moderate. Emergency physicians should continue to develop strategies with emergency medical services and cardiologists to improve the care process.[59]

Critical care units (CCUs) have reduced early mortality rates from acute myocardial infarction by approximately 50% by providing immediate defibrillation and by facilitating the implementation of beneficial interventions. These interventions include the administration of IV medications and therapy designed to do the following:

• Limit the extent of myocardial infarction

• To salvage jeopardized ischemic myocardium

• Recanalize infarct-related arteries.

The diagnose and treatment of other conditions is useful as well.[60] Alternatives for coronary recanalization include the IV administration of thrombolytic agents and catheter-based approaches.[3]

General measures commonly include the use of stool softeners to prevent constipation, straining, and consequent circulatory derangements.

Prophylaxis for stress ulcers with oral sucralfate, 1 g given twice a day, or an H2-antagonist (famotidine, ranitidine, or cimetidine), given orally or intravenously at 6- to 12-hour intervals, is appropriate for patients at high risk, including those with sepsis, hypotension or shock, bleeding diathesis, or elevated intracranial pressure or who have a requirement for prolonged mechanical intervention.

Antipyretics (eg, acetaminophen) should be used to prevent or suppress the fever that is typically seen in the first 24-48 hours and its consequent tachycardia. Patients with uncomplicated myocardial infarction need be confined to bed for only 1 day.

Physical activity should be limited (bed-chair regimen) throughout the patient's CCU stay, with gradual and carefully monitored resumption of ambulatory activity in the late hospital phase. Educational programs targeting smoking cessation, lipid lowering, and treatment of hypertension, as indicated, in addition to phased rehabilitation programs, should be started early during the hospital course for patients with uncomplicated myocardial infarction. Use of sedative, anxiolytic, and hypnotic drugs at night may be helpful. Also important are optimal communication with compassionate physicians and nurses and the reassurance it provides.

Preventive therapy in the acute hospital phase

Beta-adrenergic blockers are of benefit when given intravenously within 4 hours of the onset of pain and continued on a long-term basis. Mortality, sudden death, and infarct size are reduced in patients with Q-wave myocardial infarction when beta-blockers are given early. Patients with unstable angina also benefit through a reduction in the incidence or severity of myocardial infarction. Metoprolol or atenolol are commonly used.

Chewing an aspirin shortly after onset of chest pain is a ready means to inhibit thrombosis. In the hospital, small trials indicate benefits (decreased size of infarcts and mortality) from insulin infusion, along with glucose and potassium, presumably through an anti-apoptotic effect.

Patients with insulin-dependent diabetes mellitus and peripheral vascular disease may be treated with caution; the benefit of angioplasty is decreased in these patients.

ACE inhibitors are useful for long-term therapy and also appear to benefit patients who have no evidence of hypotension if administration is begun within the first 24 hours after the onset of myocardial infarction. Alternatives include captopril, 12.5-50 mg given orally twice a day; enalapril, 5-40 mg given orally daily or twice a day; or any of the newer agents (eg, lisinopril, quinapril, or ramipril), given in pharmacologically equivalent doses.

Treatment with both beta-adrenergic blockers and ACE inhibitors may improve the balance between myocardial oxygen supply and demand, and it may limit infarct size. Appropriate treatment of fluid status to optimize left ventricular filling pressures, maintain oxygen saturation, and control heart rate by avoiding reflex sympathoadrenal stimulation is also beneficial.

Calcium channel blockers have not been beneficial in acute myocardial infarction, and they may exert deleterious adverse effects alone or when given with other medications. Therefore, they should generally be avoided. Diltiazem may be useful for rate control in patients with atrial fibrillation. Verapamil may be useful in patients with obstructive hypertrophy.

Continuing chest pain suggestive of ischemia is an indication for cardiac catheterization and revascularization (PTCA or surgery). The decision to proceed and the choice of modality are largely made on the basis of the results of angiography and an assessment of ventricular function. IV nitroglycerin, titrated to 10-200 mcg/min to prevent hypotension, may alleviate coronary artery spasm and postinfarct angina by reducing arterial resistance and ventricular afterload. Dosages higher than this diminish systemic venous tone and blood pressure, potentially (paradoxically) exacerbating ischemia.

Diminished afterload and preload and decreased LVEDP probably mediate the favorable effects, facilitating myocardial perfusion. Tolerance to continuously administered IV nitrates occurs rapidly, often within hours.

Thrombolytic therapy has been shown to improve survival rates in ST-segment elevation myocardial infarction but is not indicated in the treatment for non–ST-segment elevation myocardial infarction. Door-to-drug time should be no more than 30 minutes.[61] Thrombolytic therapy administered within the first 2 hours can occasionally abort myocardial infarction and dramatically reduce the mortality rate.

Thrombolysis is generally preferred to PCI in cases where the time from symptom onset is less than 3 hours and if there would be a delay to PCI, greater than 1-2 additional hours to door-to-balloon time. A detailed list of contraindications and cautions for the use of fibrinolytic therapy is shown in Table 12 of the ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction—Executive Summary.

Thrombolytic treatment may be helpful in some patients, particularly those with stuttering infarcts, who are first seen 6-12 hours after the onset of symptoms. It has not been demonstrated to be effective in patients with non-Q-wave myocardial infarction or unstable angina. The clinical effectiveness of coronary thrombolysis depends on the frequency, rapidity, and persistence of recanalization. All of these factors depend not only on the intensity of fibrinolysis[62] but also on the inhibition of coagulation and platelet-induced thrombosis, which undoubtedly occur concomitantly.

In general, use of thrombolytic agents has been well demonstrated to be effective in patients aged 75 years or younger who present with suspected Q-wave myocardial infarction within 6 hours after the onset of symptoms and in whom contraindications are not present. Although the absolute risk of complications is greatest in the elderly, overall mortality reduction is at least as great in this group as in others, because the prognosis for patients with myocardial infarction that is managed conservatively is also worse for elderly patients than it is for younger patients.

Fibrinolytic agents

The first generation of fibrinolytic drugs (eg, streptokinase, urokinase, acetylated plasminogen streptokinase activator complexes [APSACs], reteplase, and novel plasminogen activator [n-PA]) indiscriminately induce activation of circulating plasminogen and clot-associated plasminogen. First-generation drugs invariably elicit a systemic lytic state characterized by depletion of circulating fibrinogen, plasminogen, and hemostatic proteins and by marked elevation of concentrations of fibrinogen degradation products in plasma.

Second-generation drugs (eg, t-PA, single-chain urokinase plasminogen activator), including agents such as tenecteplase, preferentially activate plasminogen in the fibrin domain, rather than in the circulation, as with free plasminogen. Therefore, these drugs have clot selectivity. Tenecteplase should be initiated as soon as possible after the onset of acute myocardial infarction (AMI) symptoms. In AMI patients, tenecteplase administered as a single bolus exhibits a biphasic disposition from the plasma.

In optimal regimens, these agents induce clot lysis without inducing a systemic lytic state, they are less prone than nonselective agents to predispose the patient to hemorrhage necessitating transfusion, and they are effective in inducing recanalization in 80-90% of infarct-related arteries within 90 minutes. Therefore, t-PA recanalizes 75-80% of infarct-related arteries; by contrast, IV streptokinase recanalizes approximately 50% of infarct-related arteries.

Coronary thrombolysis with IV activators of plasminogen improves ventricular function and decreases mortality, especially early after myocardial infarction and when initiated a few hours after the onset of ischemia. Even when started late (6 hours or more after the onset of myocardial infarction), restored patency of the infarct-related artery may confer an early mortality benefit, perhaps because of improved collateral blood flow and ventricular remodeling and function or decreased infarct expansion, arrhythmogenicity, ventricular aneurysm formation, and late arrhythmia associated with aneurysms that do develop.

In the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial, second-generation agents significantly improved 24-hour, 30-day, and 1-year mortality rates, as well as the rate of survival without disabling stroke.[63, 64, 65]

Plasminogen activators should not be given to patients with active internal bleeding or a bleeding diathesis; with suspected aortic dissection; who have undergone recent trauma; who have intracranial neoplasm; or who are in hypertensive crisis. Relative contraindications include prolonged or traumatic cardiopulmonary resuscitation, peptic ulcer disease, remote cerebrovascular accident, and hepatic failure. Safety has not been established for pregnant women, although safety has been established for menstruating women.

Pitfalls of coronary thrombolysis

The risks of coronary thrombolysis include bleeding, much of which is confined to sites of vascular access.[66] Marked depletion of fibrinogen or prolongation of the bleeding time may be markers of pharmacologic effects that lead to bleeding. With thrombolysis, the incidence of hemorrhagic stroke is increased, but the risk of thrombotic or embolic stroke is somewhat reduced; overall, any small increase in fatal cerebrovascular accidents is more than offset by the favorable effect on survival.

Even optimally effective coronary thrombolysis is compromised by early thrombotic reocclusion in 6-20% of patients with initial recanalization, unless vigorous conjunctive anticoagulation is started immediately.

Thrombolytic agents and mechanical revascularization

Use of thrombolytic medications and mechanical revascularization may be required. In individuals in whom fibrinolytic therapy fails to successfully recanalize the infarct-related artery (defined by ST-segment resolution < 50% at 90 min), a rescue PCI can be performed. Rescue PCI should be performed in individuals who are younger than 75 years and suitable for revascularization, if, after thrombolysis, they have evidence of acute pulmonary edema, cardiogenic shock, or hemodynamically unstable ventricular arrhythmias. Diagnostic coronary angiography post thrombolysis may be performed; however, further studies are needed to clarify the role and benefit of routine PCI to the infarct-related artery in asymptomatic patients who demonstrate successful thrombolysis.

The Occluded Artery Trial (OAT) determined that PCI to a persistently occluded infarct-related artery greater than 24 hours after onset of STEMI is not currently recommended per the latest guidelines. Facilitated PCI with thrombolysis is also not recommended in the guidelines because this approach may be harmful. Facilitated PCI refers to giving thrombolysis immediately prior to planned urgent PCI.[61]

CABG may be needed for patients whose condition fails to respond to PCI with stenting; if necessary, CABG is feasible even after the administration of IV thrombolytic agents. Despite a high perioperative mortality rate for CABG within 24 hours of failed pharmacologic thrombolysis or PCI, subsequent 1-year mortality among survivors may be as low as 2% and is not different from the rate in patients who survive CABG performed late after myocardial infarction. CABG is an option for patients in whom other efforts to establish reperfusion fail and who have ongoing major complications. Contrary to initial expectations, not all patients treated with thrombolytic drugs need early cardiac catheterization and angioplasty.

At present, IV unfractionated heparin (UFH) is routinely administered, in addition to orally administered aspirin. Alternatives include low-molecular-weight heparin (LMWH or enoxaparin), other inhibitors of coagulation (eg, hirudin, fondaparinux, bivalirudin), and antagonists of binding of fibrinogen to the platelet surface glycoprotein IIb/IIIa (GPIIb/IIIa) receptor (eg, abciximab, eptifibatide, tirofiban, orbofiban). Thienopyridines (eg, ticlopidine, clopidogrel) similarly inhibit platelet aggregation by binding to platelet adenosine diphosphate receptors, which block activation of the IIb/IIIa pathway.

Anticoagulation therapy

In the management of all patients with ACS or suspected ACS, anticoagulation therapy is the standard of care. In patients with or suspected unstable angina (UA)/NSTEMI, anticoagulation therapy should be added to antiplatelet therapy as soon as possible. In patients who have been selected to undergo an early invasive strategy for UA/NSTEMI, proven effective anticoagulant therapy includes UFH, enoxaparin, fondaparinux, and bivalirudin.

Patients in whom conservative management is initially deemed appropriate should be given the same anticoagulation options, with the exception of bivalirudin, for which data are limited. Fondaparinux is preferred in individuals with an increased bleeding risk and in whom conservative management is selected. In initial conservative therapy, both enoxaparin and fondaparinux may be preferable over UFH, unless CABG is contemplated within the first 24 hours.[28]

In UA/NSTEMI, the duration of anticoagulation in uncomplicated conservative therapy is 48 hours for UFH and the entire hospital stay is up to 8 days for LMWH or fondaparinux. In patients for whom CABG is chosen for revascularization, continue UFH up to the time of surgery, discontinue LMWH/fondaparinux 24 hours before surgery, and switch to UFH; alternatively, discontinue bivalirudin 3 hours before surgery and switch to UFH. If PCI is performed, anticoagulation therapy can be discontinued safely post successful revascularization.[28]

In STEMI, parenteral anticoagulant therapy with UFH or bivalirudin is a Class I indication in patients undergoing primary PCI.[61, 67] Data are scant with regard to heparin efficacy in patients not receiving thrombolytic therapy in the setting of myocardial infarction; however, considerable rationale exists for ancillary heparin therapy to inhibit the coagulation cascade.

The ATOLL trial’s findings suggest that 0.5 mg/kg of intravenous enoxaparin significantly reduced clinical ischemic outcomes compared with unfractionated heparin without differences in bleeding and procedural success in patients presenting with ST-elevation myocardial infarction.[68]

LMWH is commonly used because of convenient dosing, reliable therapeutic levels, and decreased incidence of heparin-induced-thrombocytopenia, especially if anticipated use is greater than 2-3 days. Assuming that a patient does not have significant renal dysfunction (serum creatinine level >2.5 mg/dL in men or >2 mg/dL in women),LMWH may be used with caution as an alternative to UFH as an ancillary therapy to fibrinolytic agents, regardless of age (note that different loading and maintenance doses are used in patients aged >75 y).[61]

As of the 2009 focused updates, the ACC/AHA STEMI and PCI guidelines permit bivalirudin as an alternative to UFH for parenteral anticoagulant therapy. Bivalirudin, a direct thrombin inhibitor, should be combined with high-dose clopidogrel load. It is recommended as reasonable anticoagulation for patients with high bleeding risk.[67]

In the final report of the HORIZONS-AMI trial, which assessed the 3-year outcomes of effectiveness and safety for bivalirudin monotherapy and paclitaxel-eluting stenting, outcomes were sustained for patients with STEMI undergoing primary PCI.[69]

Anticoagulation and Thrombolytic Therapy in STEMI

In the previous 2004 guidelines on STEMI management, patients treated with fibrinolytic therapy were recommended for heparin therapy depending on the fibrinolytic agent used.[70] In the 2007 STEMI-focused update, heparin has an established role as an adjunctive agent in patients receiving both selective and nonselective fibrinolytic therapy, with a class I indication.[61]

Although no new trials specifically focused on UFH in STEMI were performed, a number of new alternative anticoagulant therapy trials in STEMI compared the anticoagulant drug to UFH and to placebo. Given these results, the group found adjunctive anticoagulant therapy to be beneficial in STEMI. For patients receiving thrombolysis in STEMI, the proven anticoagulant adjuncts include UFH, enoxaparin, and fondaparinux.

The duration of therapy with anticoagulants should be at least 48 hour and up to 8 days. If PCI is to be performed, fondaparinux as a sole anticoagulant should not be used secondary to higher rates of catheter thrombosis during the procedure.[61] Another anticoagulant with antifactor IIa should be used to support the procedure.

Clopidogrel

Aspirin should be administered immediately if not already taken by the patient at home or administered by EMS before arrival. Use clopidogrel (Plavix) in case of aspirin allergy. Data from the CLARITY trial (CLopidogrel as Adjunctive Reperfusion Therapy Thrombolysis in Myocardial Infarction [TIMI] 28) suggest that adding clopidogrel to this regimen is safe and effective.[71] The clopidogrel dose used was 300 mg. Further studies suggest that a higher dose of clopidogrel may have added benefit.[72]

The Antiplatelet Therapy for Reduction of Myocardial Damage During Angioplasty-Myocardial Infarction (ARMYDA-6 MI) multicenter study demonstrated that in patients with STEMI, a loading dose of 600 mg clopidogrel prior to primary PCI was associated with a smaller infarct size when compared with a 300-mg loading dose.[73]

Clopidogrel use along with aspirin and anticoagulation therapy has a class I indication for the entire spectrum of acute coronary syndromes. In the ACC/AHA STEMI 2007 updated guidelines, clopidogrel at 75 mg/d should be given regardless of reperfusion therapy and should be given for at least 14 days. It is reasonable to administer a loading dose of 300 mg initially and continue this regimen long term (eg, 1 y).[61]

In the ACC/AHA UA/NSTEMI 2012 guidelines, clopidogrel should be prescribed at 75 mg/d for patients treated medically or with a bare metal stent, for a duration of at least 1 month and, ideally, up to 1 year. For patients treated with a drug-eluting stent (DES), clopidogrel needs to be continued for at least 1 year.[28] If CABG is planned, clopidogrel should be withheld 5-7 days prior to the procedure, unless the urgency of the procedure outweighs the bleeding risk.[28, 61]

In patients receiving dual antiplatelet therapy (aspirin and clopidogrel), the prophylactic use of proton pump inhibitors may reduce the rate of upper gastrointestinal bleeding.[74]  However, a study by Charlot et al found that patients treated with aspirin for first-time MI have an increased risk of adverse cardiovascular events if used in combination with PPIs.[75]  The response to clopidogrel varies among patients, and diminished responsiveness to clopidogrel has been observed. Clopidogrel is a prodrug and requires conversion to R130964, its active metabolite, through a 2-step process in the liver that involves the CYP2C19 isoenzyme. Patients who possess the genetic variants of the CYP2C19 allele or drugs (eg, omeprazole) that may inhibit the effect of CYP2C19 may decrease the conversion to the active metabolite.[28] For more information see Clopidogrel Dosing and CYP2C19.

Ticagrelor

Ticagrelor is indicated to reduce the rate of thrombotic CV events following ACS. This agent also reduces the rate of stent thrombosis in patients who have undergone stent placement for treatment of ACS. Ticagrelor is used in addition to low-dose aspirin (75-100 mg/day).[28]

In September 2015, the indication for ticagrelor was expanded to include use in patients with a history of MI more than 1 year previously.[76] Approval was based on the PEGASUS TIMI-54 study, a large-scale outcomes trial involving over 21,000 patients. PEGASUS TIMI-54 investigated ticagrelor 60 mg twice daily plus low-dose aspirin, compared to placebo plus low-dose aspirin, for the long-term prevention of CV death, heart attack, and stroke in patients who had experienced an MI 1-3 years prior to study enrollment. In patients with an MI longer than 1 year previously, treatment with ticagrelor significantly reduced the risk of CV death, MI, or stroke compared with placebo (P=0.004).[77]

Timing of clopidogrel initiation in UA/NSTEMI

Timing of clopidogrel initiation has generally fallen into 2 strategies: (1) starting as soon as possible or (2) delaying treatment until diagnostic angiography has been performed to evaluate the extent of coronary disease. In the latter strategy, if PCI is indicated, then the drug is administered “on the table.” This strategy loses the upstream benefits of reducing early ischemia; however, it minimizes the risk of major bleeding should the patient require CABG.

The ACC/AHA 2012 UA/NSTEMI guidelines describe subtle differences in the recommendation for the timing of clopidogrel initiation, depending on whether an initial conservative or invasive strategy is chosen.[28] For an initial invasive strategy, the guidelines give a class I indication to the choice of either upstream (before diagnostic angiography) clopidogrel with a loading dose or upstream intravenous glycoprotein IIb/IIIa inhibitor.

In fact, the guidelines also state that it is reasonable to consider use of both agents upstream concomitantly. In an initial conservative strategy, clopidogrel therapy with a loading dose should be added as soon as possible to anticoagulation therapy and aspirin and should be given for at least 1 month and, ideally, up to 1 year. Should the patient develop recurrent symptoms, hemodynamic instability, or acute heart failure, diagnostic angiography should be performed and management recommendation changes on upstream therapy should be the same as early invasive therapy.[28]

Aspirin use in primary prevention

Low-dose aspirin has shown substantial benefit for primary prevention of myocardial infarction and stroke, but its use must be weighed against the risk for hemorrhagic stroke and gastrointestinal bleeding.

In one study, aspirin was associated with significant reduction (12% proportional reduction) for serious vascular events (0.51% aspirin vs 0.57% control annually), but the net effect on stroke was not significant. The Antithrombotic Trialists’ (ATT) Collaboration conducted meta-analyses of serious vascular events, including myocardial infarction, stroke, and vascular death, and major bleeds in 6 primary prevention trials and in 16 secondary prevention trials that compared long-term aspirin versus control. The primary prevention trials included 95,000 individuals at low-average risk, and the secondary prevention trials included 17,000 individuals at high-average risk.[78]

The reduction in vascular events recorded in the study was largely accounted for by a 20% reduction in nonfatal myocardial infarction (0.18% vs 0.23% annually).[78] Aspirin increased risk for major gastrointestinal and extracranial bleeding. The use of aspirin for primary prevention must be advised in context with the patient’s personal risks and history.

In a systematic review of randomized, case-control, and cohort studies, Cuzick et al found that regular use of aspirin (dose range, 75-325 mg/day) for 3 years lowered the risk for MI, stroke, cancer, and premature death in average-risk adults aged 50-65 years in the general population.[79] In the adults who took prophylactic aspirin for at least 10 years, there was a reduction in relative risk for MI, stroke, and cancer events over a 15-year period that ranged between 7% for women and 9% for men.[79, 80] Moreover, aspirin use over a 20-year period had an overall 4% relative reduction in all deaths. However, higher aspirin doses did not increase the benefits associated with long-term use, and the risk of adverse events (eg, hemorrhage) increased with higher doses.[79, 80]

On September 8, 2015, the U.S. Food and Drug Administration (FDA) approved DURLAZA (aspirin), the first and only 24-hour, Extended Release Capsules, (162.5mg) for theprevention of stroke and acute cardiac events, including myocardial infarction.

Before initiating daily aspirin use, all patients should consult with their health-care providers to discuss potential serious adverse effects, including the risk of bleeding.[80]

Glycoprotein IIb/IIIa receptor inhibitors

In patients with unstable angina or NSTEMI, administer a platelet glycoprotein (GP) IIb/IIIa receptor antagonist, in addition to aspirin and anticoagulation therapy, to those with continuing ischemia or with other high-risk features and to patients in whom a PCI is planned. Eptifibatide and tirofiban are approved for this use. Abciximab[81, 82] also can be used for 12-24 hours in patients with unstable angina or NSTEMI in whom a PCI is planned within the next 24 hours.

In general, the ACC/AHA 2007 UA/NSTEMI guidelines recommend using upstream GP IIb/IIIa receptor inhibitors if PCI is to be performed post diagnostic angiography or as part of an invasive strategy. They also specifically note that abciximab is not recommended for use in patients not planning to undergo PCI.

In an initial early conservative strategy in which diagnostic angiography or stress testing will not be performed or in which findings are negative, it is recommended to stop this therapy if it has been started. Additionally, discontinue GPIIb/IIIa inhibitors if it has been determined the patient will undergo medical therapy.

If CABG is the choice of revascularization, discontinue tirofiban or eptifibatide 4 hours prior to surgery. If bivalirudin was administered as an anticoagulant and clopidogrel was given as a loading dose at least 6 hours prior to PCI, it is reasonable to omit usage of a GP IIb/IIIa inhibitor.[28]

In STEMI, data for usage of GP IIb/IIIa antagonists is available. As of the 2009 focused updates to the ACC/AHA STEMI guidelines, tirofiban and eptifibatide as well as abciximab have a class IIa recommendation for consideration at the time of primary PCI. The efficacy of GP IIb/IIIa inhibitors in preparation of patients with STEMI before angiography and PCI is not certain.[67]

Morphine sulfate

Morphine sulfate may be administered to relieve pain and anxiety. This is the analgesic of choice for anginal pain relief in STEMI.[61] For unstable angina and NSTEMI, barring contraindications, it is reasonable to administer morphine sulfate if the patient has refractory chest discomfort despite nitroglycerin use.[28]

Nitrates

Nitrates are useful for preload reduction and symptomatic relief but have no apparent impact on mortality rate in myocardial infarction. Systolic BP < 90, HR < 60 or >100, and right ventricular infarction are contraindications to nitrate use. IV nitroglycerin is indicated for relief of ongoing ischemic discomfort, control of hypertension, or management of pulmonary congestion.

Nitrates should not be administered to patients who have taken any phosphodiesterase inhibitor for erectile dysfunction within the last 24 hours (extend timeframe to 48 h for tadalafil). Their use is in symptomatic relief and preload reduction. Administer to all patients with acute myocardial infarction within the first 48 hours of presentation, unless contraindicated (ie, in right ventricular infarction).

Angiotensin-converting enzyme inhibitors

ACE inhibitors reduce mortality rates after myocardial infarction. Administer ACE inhibitors as soon as possible as long as the patient has no contraindications and remains in stable condition. An ACE inhibitor (Captopril) should be given orally within the first 24 hours of an acute coronary syndrome to patients with pulmonary congestion or LVEF less than 40% in the absence of hypotension. ACE inhibitors have the greatest benefit in patients with ventricular dysfunction. Continue ACE inhibitors indefinitely after myocardial infarction.

Angiotensin-receptor blockers

Angiotensin-receptor blockers may be used as an alternative to ACE inhibitors in patients who develop adverse effects, such as a persistent cough. An angiotensin-receptor blocker (valsartan or candesartan) should be administered to patients with ACS who are intolerant of ACE inhibitors and who have either clinical or radiologic signs of heart failure or an LVEF of less than 40%.

Beta-blockers

Beta-blockers are believed to reduce the rates of reinfarction and recurrent ischemia and should be administered to all patients with myocardial infarction unless a noteworthy contraindication exists. Both ACC/AHA 2007 guidelines for STEMI and UA/NSTEMI give oral beta-blocker usage a class I indication within the first 24 hours.

Specific contraindications to usage of this therapy include: (1) signs of heart failure, (2) evidence of a low output state, (3) increased risk for cardiogenic shock, (4) PR interval greater than 0.24 seconds (second- or third-degree heart block, and (5) active asthma or reactive airway disease.[28, 61] Metoprolol is the standard of care and is a selective beta1-adrenergic receptor blocker that decreases automaticity of contractions. Intravenous beta-blockers have a class IIa recommendation, meaning that they may also be used in ACS if the patient is hypertensive and does not have a contraindication.[28, 61, 70]

L-carnitine

Compared with placebo, L-carnitine is associated with a 27% reduction in all-cause mortality, a 65% reduction in ventricular arrhythmias, and a 40% reduction in anginal symptoms in patients experiencing an acute MI, according to a systematic review and meta-analysis of 13 studies involving 3629 patients. The beneficial impact of L-carnitine seemed to come from its ability to limit infarct size and stabilize the cardiomyocyte membrane.[83, 84]

Lidocaine

Note that routine use of lidocaine as prophylaxis for ventricular arrhythmias in patients who have experienced a myocardial infarction has been shown to increase mortality rates; its use is class indeterminate.

A retrospective study, however, showed some benefits from administration of prophylactic lidocaine upon return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest from shock-refractory ventricular fibrillation/ventricular tachycardia (VF/VT). In the study, 1296 of 1721 patients received lidocaine at first ROSC.[85, 86]

In multivariate analyses, prophylactic lidocaine reduced the risk of rearrest from recurrent VF/VT by two-thirds and the risk of recurrent cardiac arrest from nonshockable arrhythmias by about half. Use of lidocaine was also linked to a higher likelihood of admission to the hospital and survival to discharge.

In a smaller, propensity score–matched sensitivity analysis, however, lidocaine was associated with a lower incidence of recurrent VF/VT arrest (22.8% vs 38.5%) but with no other outcome benefits.[85, 86]

Calcium channel blockers

The use of calcium channel blockers in the acute setting has come into question, with some randomized, controlled trials and retrospective studies showing increased adverse effects. However, in patients with continuing/frequently recurring ischemia and in whom beta-blockers are contraindicated, nondihydropyridine calcium channel blockers such as diltiazem and verapamil can be used only in the absence of pulmonary edema, AV block, and severe left ventricular dysfunction.[28, 70]

NSAIDs

With the exception of aspirin, both selective and nonselective cyclooxygenase (COX) inhibitors should not be used during the hospitalization of patients with ACS. An increased risk in mortality may result. NSAID use in this setting is associated with an increased risk of reinfarction, hypertension, heart failure, and myocardial rupture. Therefore, patients routinely taking NSAIDs should have these discontinued at the time of presentation.[28, 61]

Further supporting evidence comes from a large Danish study, which concluded that post-discharge NSAID use following MI, even short-term (< 7 days), increases the risk of cardiovascular events in patients with established cardiovascular disease.[87] Diclofenac was associated with the highest risk 1 week. Naproxen was the only NSAID not associated with increased risk of death/re-MI over a 14-week period.

PCIs are a group of catheter-based technologies used to establish coronary reperfusion. Angiography, which provides essential knowledge of the extent of coronary disease, is performed prior to PCI. In regard to STEMI, PCI may then be performed as a primary intervention or as an intervention after thrombolysis failure. In patients presenting with unstable angina or NSTEMI, PCI is an appropriate revascularization strategy for individuals with a favorable risk factors and coronary anatomy.

The Counterpulsation and Infarct Size in Patients With Acute Anterior Myocardial Infarction (CRISP AMI) trial studied tried to determine whether routine intra-aortic balloon counterpulsation (IABC) placement prior to reperfusion in patients with anterior STEMI without shock reduces myocardial infarct size. Their findings suggest that among this group of patients, routine IABC plus primary PCI compared with PCI alone did not result in reduced infarct size.[88]

Percutaneous coronary intervention versus thrombolysis

Evidence suggests that primary PCI is more effective than thrombolysis and should be performed for confirmed STEMI, new or presumably new left bundle-branch block (LBBB), severe congestive heart failure, or pulmonary edema if it can be performed within 12 hours of symptom onset. Door-to-balloon time should be 90 minutes or less. PCI is the treatment of choice in most patients with STEMI.

In several randomized trials and registries, primary PCI (performed predominantly in experienced centers) increased patency rates of the infarct vessel at 90 minutes (85-90% for PCI vs 65% for thrombolysis).

An important advantage of performing primary PCI in myocardial infarction is the ability to achieve reperfusion of the infarct vessel with a lower risk of bleeding than that associated with thrombolytic therapy. In addition, PCI can be used to obtain instant knowledge about the extent of the underlying disease.

Patients who are treated with primary PTCA generally have shorter lengths of stay in the hospital and consume fewer medical resources than do patients treated with IV thrombolysis.

Several randomized trials have demonstrated that rapidly available primary PTCA, performed by skilled operators, for acute myocardial infarction is associated with long-term outcomes similar to those achieved with IV thrombolysis, although this comparison remains a topic of active investigation.

In systematic overviews of trials of 2635 patients who were collectively enrolled, 30-day and 6-month mortality rates were lower with primary PTCA than with thrombolysis.[89] (Door-to-balloon times correlate closely with mortality rates, making this the key measurement for any successful intervention program.) The rate of recurrent infarctions was also lower in patients treated with primary PTCA.

In addition, primary PTCA was associated with significant reductions in total stroke and hemorrhagic stroke. Therefore, primary PTCA appears to be superior to thrombolytic therapy when performed promptly in experienced centers with a well-staffed invasive angiography team.

However, the availability and accessibility of primary PCI is a very important consideration to the selection of a reperfusion strategy in patients presenting with STEMI because delays in therapy decrease myocardial salvage. If thrombolysis can be initiated 90 minutes before primary PCI is performed, then thrombolysis is preferred.[61]

Data from nonrandomized studies have suggested an advantage to the use of primary PTCA in patients with acute myocardial infarction that is complicated by cardiogenic shock. In addition, PTCA is clearly the treatment of choice for patients with contraindications to thrombolytic agents.

Whether certain subsets of patients respond better to PTCA or thrombolysis is unclear. For example, in patients with type 2 diabetes, elective PTCA is inferior to CABG, and similar or other characteristics may ultimately guide the choice among reperfusion therapies for acute myocardial infarction.

The widespread use of stenting and adjunctive IIb/IIIa therapy is improving the results of primary PCI. In one trial, coronary stenting and abciximab in patients with acute myocardial infarction led to a greater degree of myocardial salvage and a better clinical outcome than did fibrinolysis with thrombolytic therapy.[90] Improvements in short- and long-term outcomes, however, depend highly on the speed with which reperfusion is achieved.

In a study by Cantor et al, a significant decrease in ischemic complications was observed in high-risk patients with STEMI who presented at hospitals without PCI capabilities who were treated with fibrinolysis and then transferred to another hospital for PCI.[91] This study randomized 1059 patients to either standard treatment (which, if needed, included rescue PCI or delayed angiography) or immediate transfer to another hospital, where they received PCI within 6 hours following fibrinolysis. All patients received aspirin, tenecteplase, and anticoagulation (heparin or enoxaparin), and clopidogrel was recommended.

The choice of primary PCI should be individualized to each institution and to the patient's presentation and timing. PCI in patients whose arteries have been occluded for more than 24 hours appears to offer no added benefit over medical treatment.

Considerations in percutaneous coronary intervention

Elective PCI should be considered for most patients receiving thrombolytic therapy in whom ischemia develops at rest, during ambulation in the hospital, or during a prehospital discharge exercise test. Complete revascularization within 3 months of myocardial infarction appears to offer outcomes better than those of repair of the infarct-related lesion alone.

A study by Vlaar et al supports existing guidelines in that multivessel PCI in patients with STEMI is associated with higher mortality. Staged PCI (for those with significant nonculprit lesions) is associated with better outcomes.[92]

Only an experienced operator should perform primary PTCA, and PTCA should be performed only where the appropriate facilities are available. Operators should have at least 75 cases per year, while the center should perform at least 200 cases per year as per the recommendations of the ACC.

The 2009 focused updates to the ACC/AHA STEMI and PCI guidelines include recommendations for interventions and supportive measures for PCI[67] :

• Prasugrel is a reasonable alternative to clopidogrel for antiplatelet therapy during PCI, unless the patient has a history of stroke or transient ischemic attack.

• Thrombus aspiration is reasonable for primary PCI.

• Fractional flow reserve can be useful to determine whether a specific lesion should be stented.

An updated meta-analysis of 25 trials including 5534 patients found that thrombus aspiration before angioplasty reduced major adverse cardiac events (MACE) but did not affect infarction size.[93, 94] Aspiration thrombectomy was linked with significantly (P< 0.0001) higher rates of TIMI (Thrombolysis In Myocardial Infarction) 3 blush post procedure (63.6% vs 48.5%) and complete ST-segment resolution (55.8% vs 44.3%).[94] During follow-up (average, 5.9 months), all-cause mortality (the primary endpoint) was significantly lower with aspiration thrombectomy than with PCI alone (2.7% vs 3.9%; P = 0.049).

Drawbacks, contraindications, and risk factors for percutaneous coronary intervention

Diagnostic coronary angiography post thrombolysis may be performed; however, further studies are needed to clarify the role and benefit of routine PCI to the infarct-related artery in asymptomatic patients who demonstrate successful thrombolysis.[61] The Occluded Artery Trial (OAT) determined that PCI to a persistently occluded infarct-related artery greater than 24 hours after onset of STEMI is not currently recommended per the latest ACC/AHA 2007 guideline update.[28, 95]

Facilitated PCI with thrombolysis also is not recommended in the guidelines because this approach may be harmful. Facilitated PCI refers to giving thrombolysis immediately prior to planned, urgent PCI.[61]

A drawback of PCI is the need for 24-hour availability of an angioplasty suite with the required staff and the availability of backup cardiothoracic capabilities. Primary PCI for STEMI should be performed at hospitals with readily available cardiothoracic surgery. (“Readily available” may be defined as the ability to transport patients quickly to a hospital with cardiothoracic capabilities.)

No absolute contraindications are described for coronary arteriography. Relative contraindications include the following:

• Unexplained fever

• Untreated infection

• Severe anemia with hemoglobin level less than 8 g/dL

• Severe electrolyte imbalance

• Severe active bleeding

• Uncontrolled systemic hypertension

• Digitalis toxicity

• Previous allergy to contrast material but no pretreatment with corticosteroids

• Ongoing stroke

• Acute renal failure

• Decompensated CHF

• Severe coagulopathy

• Diabetic patients with Cr greater than 2

• Patients on metformin (Glucophage) or other oral hypoglycemic agents

• Active endocarditis

Risk factors for clinically significant complications after catheterization include advanced age, hemodynamic instability, multisystemic disease, large infarctions, bleeding disorders, and extensive atherosclerosis in the aorta or access arteries.

Disadvantages of primary PTCA include the fact that the procedure is highly dependent on the operator's skill and that immediate access to highly skilled operators is necessary.[96]

Percutaneous coronary intervention in high-risk patients

Primary PCI appears to have a particular advantage over thrombolysis for the management of high-risk myocardial infarction patients, such as those with diabetes and the elderly. In an analysis of patients who were receiving Medicare in the Cooperative Cardiovascular Project database, primary PCI improved 30-day and 1-year survival. The benefits of primary PCI in the elderly persisted after stratification by the number of myocardial infarction patients cared for at individual hospitals and the presence of on-site angiography. When the transit time to such a facility is 90 minutes or more, facilitated half-dose thrombolysis followed by PCI may be effective. The risk of this approach may be lower than that of full-dose thrombolysis, and patency rates are greater than that of late PCI without lysis.

Availability of percutaneous coronary intervention

Although reports from individual community hospitals replicating the results in randomized trials may be found in the literature, less than 20% of hospitals in the United States and less than 10% of hospitals in Europe can perform primary PCI. An even smaller percentage of hospitals are performing PCI on an emergency basis 24 hours a day, 7 days a week. Whether low-volume PCI centers with relatively inexperienced investigators can replicate the encouraging results reported to date remains to be determined. In addition, whether on-site cardiac surgical backup is a necessary component of a primary PCI strategy for myocardial infarction is unclear.

Emergent or urgent CABG surgery is indicated in patients in whom angioplasty fails and in patients who develop mechanical complications, such as a ventricular septal defect, LV, or papillary muscle rupture.

If, after medical therapy with fibrinolytic drugs, percutaneous intervention with angioplasty, surgery, or spontaneous resolution, coronary blood flow does not resume relatively promptly, good myocardial perfusion may not be achieved despite restoration of luminal patency.[97] This situation is known as the no-reflow phenomenon; it occurs because of swelling of endothelial cells, formation of platelet and leukocyte plugs, or complement-mediated microvascular inflammation.

Interventionalists have begun to embrace new treatment strategies, such as the use of stenting and IV platelet GPIIb/IIIa inhibitors, to improve results of PTCA in acute myocardial infarction. Stents that elute drugs such as sirolimus and paclitaxel may inhibit endothelial proliferation, prevent early closure, and improve results. This stenting appears to be more effective than brachytherapy (irradiation).

Patients with evolving chest pain and ST-segment elevations that persist for 90 minutes after the administration of a thrombolytic agent may be candidates for emergency catheterization, and, if the infarct-related vessel is occluded, for “rescue” PCI.[98]

Local injection of progenitor cells, growth factors, or genes may stimulate vascular development. Investigators in a double-blinded study, the Reinfusion of Enriched Progenitor Cells And Infarct Remodeling in Acute Myocardial Infarction (REPAIR-AMI) study, examined 204 patients with acute STEMI; they reported demonstrated greater improvement in LVEF among patients receiving intracoronary progenitor cell infusion than among patients given placebo.[99]

Some clinical trial results suggest that intracoronary delivery of autologous bone marrow mononuclear cells (BMCs) have improved LV function when administered within the first week following myocardial infarction. The LateTIME Randomized Trial tested whether intracoronary delivery of autologous BMCs improved global and regional LV function compared with placebo when delivered 2-3 weeks following first myocardial infarction. The results suggest that those patients with myocardial infarction and LV dysfunction following reperfusion with PCI show little improvement from this therapy.[100]

ICDs may be unnecessary in select post-MI patients with severe LV dysfunction and negative EPS

Zaman et al reported that patients with severe LV dysfunction and a negative electrophysiology study (EPS) showing no inducible ventricular tachycardia (VT) have low long-term rates of arrhythmia or death without receiving an implantable cardioverter defibrillator (ICD).[101, 102] The rates were shown to be similar to those observed in patients with preserved LV ejection fraction (EF).[102] In their study, LVEF assessment was performed on consecutive patients treated with coronary angioplasty for ST-segment-elevation MI (STEMI), including 128 patients with an LVEF of 30% or less or with an LVEF of 35% or less with New York Heart Association (NYHA) class 2 or 3 heart failure, as well as 1286 control patients with an LVEF greater than 40% (not eligible for EPS).[101, 102]

ICDs were implanted in less than 0.1% of control patients, 4% of patients with a negative EPS, and 90% of those with a positive EPS.[101, 102] At 3-year follow-up, 91.8% of controls and 93.4% of EPS-negative patients were alive and without arrhythmia, whereas 62.7% of patients with LV dysfunction and a positive EPS were alive and without arrhythmia.[101, 102]

Elderly patients with acute myocardial infarction are at increased risk of developing complications. Treat these patients aggressively. Elderly patients have an increased risk of bleeding with thrombolytic therapy, but they also have the most to gain from this treatment.

Very elderly patients should undergo primary angioplasty if available, but they should receive thrombolytic agents if excessive delay is anticipated before angioplasty can be performed.

Initially, keep the patient on nothing by mouth (NPO) until his or her condition has been stabilized and treated. Following the patient’s initial therapy and admission, a dietitian should instruct the patient regarding appropriate diet, as recommended by the AHA. A low-salt, low-fat, and low-cholesterol diet is generally recommended.

Confine patients to bed rest to minimize oxygen consumption until reperfusion and initial therapy are complete. This usually lasts about 24-48 hours; after that, the patient's activity may be accelerated slowly as tolerated and as the clinical situation allows. Initiate cardiac rehabilitation prior to discharge.

Complications of myocardial infarction include arrhythmic complications, mechanical complications, left ventricular aneurysm, ventricular septal rupture, associated right ventricular infarction, pseudoaneurysm, and other miscellaneous complications, all of which are discussed in general below. For more information, see Complications of Myocardial Infarction.

Arrhythmic complications

Cardiac arrhythmias are not uncommon during and immediately after an acute myocardial infarction. Of all patients who have an acute myocardial infarction, about 90% develop some form of cardiac arrhythmia. In 25% of patients, such rhythm abnormalities manifest within the first 24 hours. In this group of patients, the risk of serious arrhythmias, such as VF, is greatest in the first hour and declines thereafter. The incidence increases with an STEMI and decreases with NSTEMI.

The clinician must be aware of these arrhythmias, in addition to reperfusion strategies, and he or she must treat those that require intervention to avoid exacerbation of ischemia and subsequent hemodynamic compromise. Most peri-infarct arrhythmias are benign and self-limited. However, those that result in hypotension, increase myocardial oxygen requirements, and/or predispose the patient to develop additional malignant ventricular arrhythmias should be aggressively monitored and treated.

Mechanical complications

The 3 major mechanical complications of myocardial infarction, each of which can cause cardiogenic shock, are as follows:

• Ventricular free wall rupture

• Ventricular septal rupture

• Papillary muscle rupture with severe mitral regurgitation

Left ventricular aneurysm

Left ventricular aneurysm is defined as a localized area of myocardium with abnormal outward bulging and deformation during systole and diastole. The rate of left ventricular aneurysms after acute myocardial infarction is approximately 3-15%. Risk factors for these aneurysms after acute myocardial infarction include the following:

• Female sex

• Total occlusion of the LAD artery

• Single-vessel disease

• Absence of previous angina

On clinical evaluation, ventricular aneurysms may be recognized late, with symptoms and signs of HF, recurrent ventricular arrhythmia, or recurrent embolization.

Ventricular septal rupture

Ventricular septal rupture is a rare, but lethal, complication of myocardial infarction. The event occurs 2-8 days after an infarction and often precipitates cardiogenic shock. The differential diagnosis of postinfarction cardiogenic shock should exclude free ventricular wall rupture and rupture of the papillary muscles. To avoid the high morbidity and mortality associated with this disorder, patients should undergo emergent surgery.[103, 104] Concomitant coronary artery bypass may be required. Developments in myocardial protection and improved prosthetic materials have contributed greatly to successful management of ventricular septal rupture.[105] Long-term survival can be achieved in patients who undergo prompt surgery.

Ventricular rupture occurs in the interventricular septum or the left ventricular free wall. Rupture in either location is a catastrophic event, with the mortality rate being greater than 90%. Prompt recognition, stabilization, and surgical repair are crucial to any hope of patient survival. Ventricular rupture is more common in women, patients with hypertension, and those receiving nonsteroidal anti-inflammatory drugs (NSAIDs) or steroids. An echocardiogram can usually define the abnormality, and a right heart catheterization can show an oxygen saturation step-up in the case of a septal rupture.

Associated right ventricular infarction

Approximately one third of patients with inferior myocardial infarction develop RV infarction. RV infarction presents a special challenge because the adjunctive therapy, other than reperfusion, is somewhat different.

A right-sided ECG with greater than 1 mm ST elevation in V3 R or V4 R leads describes an RV infarct. An echocardiogram may be helpful in confirming the diagnosis. On physical examination, signs of right heart failure, such as elevated jugular venous pulsation, right-sided S3, Kussmaul sign, or hypotension, may be present, and the patient may have clear lung fields.

The patient becomes volume dependent to maintain adequate LV and RV filling. Occasionally, dobutamine may be needed, or even an intra-aortic balloon pump for hemodynamic support.

Avoid nitrates or any medications that lower preload in this setting. A pulmonary artery catheter can be helpful in guiding therapy.

For more information, see Right Ventricular Infarction.

Pseudoaneurysm

Complications of myocardial infarction, such as pseudoaneurysm, are confirmed by means of echocardiography, MRI, or contrast-enhanced CT scanning. Imaging of a pseudoaneurysm typically shows a relatively narrow neck and a complete absence of muscle in the wall of the pseudoaneurysm, unlike a true aneurysm, which has a rim of myocardial wall that may be identified on angiograms by the presence of mural vessels.

Miscellaneous complications

Left ventricular mural thrombus is a well-known complication of acute myocardial infarction and frequently develops after anterior infarcts of the LV wall. The incidence of left ventricular mural thrombus as a complication of acute myocardial infarction ranges from 20-40% and may reach 60% in patients with large, anterior-wall acute myocardial infarctions who are not treated with anticoagulant therapy. Left ventricular mural thrombus is associated with a high risk of systemic embolization. Anticoagulant therapy may substantially decrease the rate of embolic events by 33% compared with no anticoagulation.

The incidence of early pericarditis after myocardial infarction is approximately 10%, and this complication usually develops within 24-96 hours. Pericarditis is caused by inflammation of pericardial tissue overlying infarcted myocardium. The clinical presentation may include severe chest pain, usually pleuritic, and pericardial friction rub.

Before the era of reperfusion, the incidence of post-myocardial infarction syndrome (Dressler syndrome) ranged from 1-5% after acute myocardial infarction, but this rate has dramatically declined with the advent of thrombolysis and coronary angioplasty.

For more information, see Complications of Myocardial Infarction.

A study showed that the transfer of patients to an invasive-treatment center for primary PCI is superior to on-site fibrinolysis provided that the transfer can be accomplished within 2 hours. Transfer should be considered for those patients who are likely to benefit from PCI or cardiac surgery but who are in an institution where access to such interventions is not immediate. The benefits of transferring such a patient must outweigh the risks. Patients for whom transfer might be considered include the following:

• Patients with new or worsening hemodynamically significant mitral regurgitant murmurs

• Patients with known or suspected critical aortic stenosis and either ongoing ischemia or hemodynamic instability

• Patients who have received thrombolysis and fail to reperfuse

• Patients with significant LV dysfunction or cardiogenic shock

In an aforementioned study by Cantor et al, a significant decrease in ischemic complications was observed in high-risk patients with STEMI who were treated with fibrinolysis and transferred for PCI within 6 hours following fibrinolysis.[91] This study randomized 1059 patients to either standard treatment (ie, if needed, included rescue PCI, or delayed angiography) or immediate transfer to another hospital and PCI within 6 hours following fibrinolysis. All patients received aspirin, tenecteplase, and anticoagulation (heparin or enoxaparin), and clopidogrel was recommended.

The 2009 focused updates to the ACC/AHA STEMI and PCI guidelines recommend that high-risk STEMI patients who receive fibrinolytic primary reperfusion therapy be transferred to a PCI-capable facility as soon as possible. The clinician should consider starting anticoagulant plus antiplatelet treatment before and during the transfer. The same transfer and treatment may be considered for similar patients not at high risk.[67]

Cigarette smoking is a major risk factor for coronary artery disease. The risk of recurrent coronary events decreases 50% at 1 year after smoking cessation. Provide all patients who smoke with guidance, education, and the support needed to avoid smoking. Bupropion has been shown to increase the chances of patients' success in achieving smoking cessation.

Varenicline (Chantix) has also been shown to aid in smoking cessation, however, a meta-analysis of double-blind, randomized controlled trials found a 72% increased risk of serious adverse cardiovascular events in patients receiving varenicline (1.06%) compared with those receiving a placebo (0.82%).[106] Serious adverse cardiovascular events were defined as myocardial infarction, unstable angina, coronary revascularization, coronary artery disease, arrhythmias, transient ischemic attacks, stroke, sudden death or cardiovascular-related death, or congestive heart failure.[106]

A meta-analysis reported by the FDA in 2012 also showed an increased risk of serious adverse cardiovascular events in patients receiving varenicline compared to those receiving placebo. Although the events were uncommon in both groups and the risk was not statistically significant, data analysis points to the drug as the likely cause.[107]

Extreme caution should be used when considering varenicline for patients with known cardiovascular problems.

Mild alcohol consumption has been associated with a decreased risk of stroke and myocardial infarction. Cautiously consider recommending and discussing alcohol use on a case-by-case basis.

Antioxidant therapy, including vitamin E, has not shown clear benefit in the prevention of coronary events.

Do not use long-term anticoagulant (ie, warfarin) therapy routinely in post–myocardial infarction patients, but employ it as an alternative in patients who cannot take antiplatelet agents. Patients with known left ventricular thrombus, atrial fibrillation, or severe wall motion abnormalities have shown benefit from long-term anticoagulation, maintaining the international normalized ratio (INR) between 2 and 3.

Low-dose aspirin has shown substantial benefit for primary prevention of myocardial infarction and stroke, but its use must be weighed against the risk for hemorrhagic stroke and gastrointestinal bleeding. A study in the United Kingdom suggests that the discontinuation of low-dose aspirin therapy in individuals with a history of cardiovascular events are at an increased risk of nonfatal myocardial infarction compared with those who continue treatment.[108]

In the aforementioned Antithrombotic Trialists' (ATT) Collaboration study, aspirin was associated with significant reduction (12% proportional reduction) for serious vascular events (0.51% aspirin vs 0.57% control annually), but the net effect on stroke was not significant.[78] The use of aspirin for primary prevention must be advised in context with the patient’s personal risks and history.

In 2010, the American Heart Association-American Stroke Assocation issued its guidelines for the primary prevention of stroke. They advised that screening patients 65 years of age and older for atrial fibrillation (AF) in the primary care settings using pulse taking followed by an ECG may be useful. They also advised that adjusted-dose warfarin should be used for all patients with nonvalvular AF (target INR 2-3). Aspirin is recommended for low and moderate-risk patients with AF; for high-risk patients unsuitable for anticoagulation, a combination of clopidogrel and aspirin may offer better protection against stroke than aspirin alone.[109]

In 2014, the FDA released study results of more than 134,000 Medicare patients in which there was no increased risk of MI with dabigatrin (Pradaxa) compared with warfarin.[110, 111] Dabigatrin was also associated with a lower risk of clot-related strokes, bleeding in the brain, and death than warfarin. However, the risk of major gastrointestinal bleeding was higher in the dabigatrin-treated group than the group receiving warfaran. As a result of the findings, the FDA still considers dabigatrin to have a favorable benefit to risk profile.[110, 111]

Do not start post–myocardial infarction patients on postmenopausal hormone therapy. However, patients who have already been undergoing such treatment for more than 1 year may be continued on it without increased risk.

In a case-control study of 559 Australian patients, 275 with acute MI (AMI) and 284 without, vaccination against the influenza virus reduced the risk of ischemic events, even though the influenza virus itself was not a significant predictor of AMI.[112, 113]

In all, 12.4% of the vaccinated subjects and 6.7% of the control subjects had influenza (odds ratio, 1.97; 95% confidence interval [CI], 1.09–3.54).[113] After adjustment for confounding variables (eg, age, male sex, high cholesterol levels, current smoker status, and influenza vaccination in the study year), influenza exposure was not associated with a risk of AMI despite the association observed in univariate analysis. In the multivariate analysis, flu vaccination was associated with a 45% reduction in AMI risk.

The decision to administer a thrombolytic agent may be made by the emergency physician, with or without the input of a cardiologist, depending on institutional protocol. In a center with the full range of treatment options, an expeditious phone consultation with a cardiologist would seem to be a wise choice to ascertain the best possible option for the patient.

Obtain cardiologic consultation immediately if primary PCI is considered. Otherwise, such consultation may be obtained as needed and upon admission. Consultation may be obtained sooner if the patient presents with significant heart failure, mechanical complications, arrhythmias, or other complicating factors.

A cardiologist should be consulted for the following:

• Patients who may benefit from PCI, including "rescue PCI," with transfer if required, for patients in whom thrombolysis for STEMI fails to achieve reperfusion

• Patients in cardiogenic shock

• Patients with hemodynamically significant new or worsening murmur

• Patients who are not candidates for thrombolytic intervention because of a contraindication

• Intractable angina despite medications

• Severe pulmonary congestion

• Late presentation (>3 h but no more than 12 h)

• Where the diagnosis is in doubt

Note that PCI door-to-balloon time should be less than 90 minutes.

Admit patients with myocardial infarction to a coronary care unit. Monitor patients carefully for arrhythmia, recurrent ischemia, and other possible complications. The patient may be transferred to a telemetry unit 24-48 hours after admission if no complications occur. Hospitalize the patient for approximately 4-5 days after myocardial infarction. Patients who undergo primary PCI or have an immediate cardiac catheterization may be discharged sooner if their hospital course is without incident.

Perform a coronary angiography on high-risk patients prior to discharge to evaluate their need for revascularization. In the case of patients who have not had a cardiac catheterization and have no complications, perform a submaximal stress test prior to discharge to assess their subsequent risk. To stratify mortality risk after PCI for acute myocardial infarction, Negassa et al developed a prognostic classification model. Patients can be readily stratified into risk categories using this tree-structured model.[114]

Wang et al analyzed Medicare and Medicaid data, examining hospitals for adherence to the AHA Get with the Guidelines recommendations after myocardial infarction and for heart failure. Those who adhered to guidelines for both had reduced in-hospital mortality (hazard ratio 0.79) compared with those who adhered to one guideline or neither one.[115]

Arrange for follow-up within 2 weeks of discharge. Arrange for cardiac rehabilitation.

Current guidelines strongly recommend the use of aldosterone antagonists after MI for patients with left ventricular systolic dysfunction concomitant with either clinical heart failure or diabetes mellitus. However, an analysis of data on 202,213 US patients discharged following an acute myocardial infarction found that only 14.5% of eligible patients received aldosterone antagonists at the time of discharge. Among eligible patients who were discharged on otherwise optimal medical therapy (68.9%), 16.1% were prescribed aldosterone antagonists.[116]

The long-term use of aspirin in patients who have had a myocardial infarction results in significant reduction in subsequent mortality rate. The prescription of 75-162 mg/d of aspirin indefinitely is a class I recommendation for patients with NSTEMI who are treated medically without stenting, according to the 2011 update of the ACC Foundation (ACCF)/AHA guidelines on unstable angina/NSTEMI.[117] Beta-blocker therapy has confirmed therapeutic benefit in survivors of acute myocardial infarction. This therapy is most beneficial in patients with the highest risk.

The use of ACE inhibitors in patients with known coronary artery disease has been shown to reduce mortality rate.

Many trials have shown a clear benefit from lipid-lowering therapy in the secondary and primary prevention of coronary artery disease. The National Cholesterol Education Panel has set guidelines for target cholesterol levels. In general, patients who have experienced myocardial infarction should achieve a low-density a lipoprotein (LDL) level of less than 100 mg/dL, a high-density lipoprotein (HDL) level of greater than 40 mg/dL, and a triglyceride level of less than 200 mg/dL. High-risk patients should be treated to a target LDL level of less than 70 mg/dL.

Schwartz et al showed in the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) trial that initiating atorvastatin during hospitalization for an acute coronary syndrome, irrespective of lipid levels, reduces the frequency of recurrent ischemic events. This treatment significantly reduced the frequency of the combined end point of death, recurrent death, myocardial infarction, or worsening unstable angina requiring hospitalization.[118]

Clopidogrel should be prescribed for a year following discharge if the patient has no contraindications and cost is not prohibitive. To reduce the risk of bleeding, the aspirin dose can be reduced to 81 mg.

Data from a study of 24,317 consecutive survivors of an acute MI with atrial fibrillation and known serum creatinine show that regardless of the severity of renal dysfunction, the 1-year risk of death, MI, or stroke was significantly lower among patients prescribed warfarin at discharge compared with those who were not. Of the total patients, 5,292 (21.8%) were prescribed warfarin at discharge, and 51.7% had chronic kidney disease, defined as an estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73m2.[119, 120]

At 1 year, after adjustment for age, sex, center, eGFR, preexisting cardiovascular (CV) comorbidities and cancer, syndrome at presentation, revascularization at index hospitalization, and discharge CV medication, the hazard ratio for death, MI, or ischemic stroke among patients who received warfarin was 0.73 for all patients, 0.73 for those with eGFR >60, 0.73 for those with eGFR >30 to 60, 0.84 for those with eGFR >15 to 30, and 0.57 for those with eGFR < 15. The adjusted risk of bleeding was not significantly higher in patients who received warfarin in any eGFR group.[119, 120]

The goals of pharmacotherapy for myocardial infarction are to reduce morbidity and to prevent complications. The main goals of ED medical therapy are rapid IV thrombolysis and/or rapid referral for PCI, optimization of oxygenation, reduction of cardiac workload, and pain control.

Class Summary

Antiplatelet agents have a strong mortality benefit. There is an increased risk of bleeding in cases of emergency coronary artery bypass graft (CABG).

Aspirin (Ascriptin, Bayer Aspirin, Aspirtab, Ecotrin, Durlaza)

Early administration of aspirin in patients with acute myocardial infarction has been shown to reduce cardiac mortality rate by 23% in the first month.

Clopidogrel (Plavix)

Clopidogrel selectively inhibits adenosine diphosphate (ADP) binding to platelet receptors and subsequent ADP-mediated activation of glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation.

Clopidogrel may have a positive influence on several hemorrhagic parameters and may exert protection against atherosclerosis, not only through inhibition of platelet function but also through changes in the hemorrhagic profile.

This agent has been shown to decrease cardiovascular death, myocardial infarction, and stroke in patients with acute coronary syndrome (ie, unstable angina, non-ST elevation MI [NSTEMI], or ST-elevation MI [STEMI]).

Ticagrelor (Brilinta)

Ticagrelor and its major metabolite reversibly interact with the platelet P2Y12 ADP-receptor to prevent signal transduction and platelet activation. This agent is indicated to reduce the rate of thrombotic cardiovascular events in patients with acute coronary syndrome (ACS)—that is, unstable angina, non-ST elevation MI (NSTEMI), or ST-elevation MI (STEMI). Ticagrelor also reduces the rate of stent thrombosis in patients who have undergone stent placement for treatment of ACS, and it is indicated in patients with a history of MI more than 1 year previously. Patients can be transitioned from clopidogrel to ticagrelor without interruption of antiplatelet effect.

Prasugrel (Effient)

Prasugrel is a prodrug, a thienopyridine that inhibits platelet activation and aggregation through irreversible binding of active metabolite to adenosine phosphate (ADP) platelet receptors (specifically, P2Y12 receptor)

It is indicated for reduction of thrombotic cardiovascular events (including stent thrombosis) in patients with acute coronary syndrome (ACS) managed by means of percutaneous coronary intervention (PCI) who have either (a) unstable angina or non-ST-elevation MI (NSTEMI) or (b) ST-elevation MI (STEMI) when managed with primary or delayed PCI.

The use of prasugrel is not recommended for patients with a history of stroke or transient ischemic attack (TIA).

Vorapaxar (Zontivity)

Vorapaxar reversibly inhibits protease-activated receptor 1 (PAR-1) which is expressed on platelets, but its long half-life makes it effectively irreversible. It is indicated to reduce thrombotic cardiovascular events in patients with a history of MI or with peripheral arterial disease. It is not used as monotherapy, but added to aspirin and/or clopidogrel.

Class Summary

Antithrombotic agents, which include heparin, bivalirudin, and enoxaparin, prevent the formation of thrombi associated with myocardial infarction and inhibit platelet function by blocking cyclooxygenase and subsequent platelet aggregation. Antiplatelet therapy has been shown to reduce mortality rates by reducing the risk of fatal myocardial infarctions, fatal strokes, and vascular death. Unfractionated intravenous heparin and fractionated low-molecular-weight subcutaneous heparins are the 2 choices for initial anticoagulation therapy.

Bivalirudin (Angiomax)

Bivalirudin, a synthetic analogue of recombinant hirudin, inhibits thrombin; it is used for anticoagulation in patients with unstable angina who are undergoing PCI. With provisional use of glycoprotein IIb/IIIa inhibitor (GP IIb/IIIa inhibitor), bivalirudin is indicated for use as an anticoagulant in patients undergoing PCI. Potential advantages over conventional heparin therapy include more predictable and precise levels of anticoagulation, activity against clot-bound thrombin, absence of natural inhibitors (eg, platelet factor 4, heparinase), and continued efficacy following clearance from plasma (because of binding to thrombin).

Heparin

Heparin augments the activity of antithrombin III and prevents the conversion of fibrinogen to fibrin. Heparin does not actively lyse, but it is able to inhibit further thrombus formation and prevents reaccumulation of a clot after spontaneous fibrinolysis.

Enoxaparin (Lovenox)

Enoxaparin enhances the inhibition of factor Xa and thrombin by increasing antithrombin III activity. In addition, it preferentially increases the inhibition of factor Xa. Enoxaparin is indicated for the treatment of acute STEMI managed medically or with subsequent PCI. It is also indicated for prophylaxis of ischemic complications caused by unstable angina and non-Q-wave myocardial infarction.

Dalteparin (Fragmin)

Enhances inhibition of factor Xa and thrombin by increasing antithrombin III activity. In addition, preferentially increases inhibition of factor Xa.

Except in overdoses, no utility exists in checking PT or aPTT, because aPTT does not correlate with anticoagulant effect of fractionated LMWH.

Average duration of treatment is 7-14 d.

Class Summary

Glycoprotein IIb/IIIa inhibitors prevent acute cardiac ischemic complications in unstable angina that is unresponsive to conventional therapy.

Abciximab (ReoPro)

Abciximab is a chimeric human-murine monoclonal antibody. It binds to the platelet surface glycoprotein IIb/IIIa (GPIIb/IIIa) receptor with high affinity, preventing the binding of fibrinogen and reducing platelet aggregation by 80%. Inhibition of platelet aggregation persists for as long as 48 hours after infusion stops.

Tirofiban (Aggrastat)

Tirofiban is a nonpeptide antagonist of the glycoprotein IIb/IIIa receptor. It is a reversible antagonist of fibrinogen binding, and when administered intravenously, it inhibits platelet aggregation by more than 90%.

Eptifibatide (Integrilin)

Eptifibatide is a cyclic peptide that also reversibly inhibits platelet aggregation by binding to the glycoprotein IIb/IIIa receptor. Blocks platelet aggregation and prevents thrombosis.

Class Summary

Vasodilators relieve chest discomfort by improving myocardial oxygen supply, which in turn dilates epicardial and collateral vessels, improving blood supply to the ischemic myocardium.

Nitroglycerin IV (Nitro-Dur)

Nitroglycerin relaxes vascular smooth muscle via stimulation of intracellular cyclic guanosine monophosphate production, causing a decrease in blood pressure. Nitrates are useful for preload reduction and symptomatic relief but have no apparent impact on mortality rate in myocardial infarction.

Class Summary

This category of drugs has the potential to suppress ventricular ectopy due to ischemia or excess catecholamines. In the setting of myocardial ischemia, beta-blockers have antiarrhythmic properties and reduce myocardial oxygen demand secondary to elevations in heart rate and inotropy.

Metoprolol (Lopressor)

This category of drugs, which includes metoprolol (Lopressor) and esmolol (Brevibloc), has the potential to suppress ventricular ectopy due to ischemia or excess catecholamines. In the setting of myocardial ischemia, beta-blockers have antiarrhythmic properties and reduce myocardial oxygen demand secondary to elevations in heart rate and inotropy.

Esmolol (Brevibloc)

Esmolol is a useful drug for patients at risk of experiencing complications from beta-blockers, particularly reactive airway disease, mild-to-moderate left ventricular dysfunction, and peripheral vascular disease. Its short half-life of 8 minutes allows for titration to desired effect, with the ability to stop quickly if necessary.

Atenolol (Tenormin)

Used to treat hypertension. Selectively blocks beta1-receptors with little or no effect on beta 2 types. Beta-adrenergic blocking agents affect blood pressure via multiple mechanisms. Actions include negative chronotropic effect that decreases heart rate at rest and after exercise, negative inotropic effect that decreases cardiac output, reduction of sympathetic outflow from the CNS, and suppression of renin release from the kidneys. Used to improve and preserve hemodynamic status by acting on myocardial contractility, reducing congestion, and decreasing myocardial energy expenditure.

Beta-adrenergic blockers reduce inotropic state of left ventricle, decrease diastolic dysfunction, and increase LV compliance, thereby reducing pressure gradient across LV outflow tract. Decreases myocardial oxygen consumption, thereby reducing myocardial ischemia potential. Decreases heart rate, thus reducing myocardial oxygen consumption and reducing myocardial ischemia potential.

During IV administration, carefully monitor blood pressure, heart rate, and ECG.

Class Summary

ACE inhibitors may prevent the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion. ACE inhibitors reduce mortality rates after myocardial infarction. Administer ACE inhibitors as soon as possible as long as the patient has no contraindications and remains in stable condition. ACE inhibitors have the greatest benefit in patients with ventricular dysfunction.

Captopril

Captopril has a short half-life, which makes it an important drug for initiation of ACE inhibitor therapy. It can be started at a low dose and titrated upward as needed and as the patient tolerates.

Enalapril (Vasotec, Epaned)

Enalapril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion. This agent helps to control blood pressure and proteinuria.

Enalapril decreases pulmonary-to-systemic flow ratio in the catheterization laboratory and increases systemic blood flow in patients with relatively low pulmonary vascular resistance. It has a favorable clinical effect when administered over a long period. Enalapril helps to prevent potassium loss in the distal tubules. The body conserves potassium; thus, less oral potassium supplementation is needed.

Quinapril (Accupril)

Quinapril prevents conversion of angiotensin I to angiotensin II, resulting in increased levels of plasma renin and a reduction in aldosterone secretion.

Lisinopril (Zestril, Prinivil)

Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion.

Class Summary

Angiotensin-receptor blockers may be used as an alternative to ACE inhibitors in patients who develop adverse effects, such as a persistent cough, although initial trials need to be confirmed. An angiotensin-receptor blocker should be administered to patients with STEMI who are intolerant of ACE inhibitors and who have either clinical or radiologic signs of heart failure or an LVEF of less than 40%.

Irbesartan (Avapro)

Blocks vasoconstrictor and aldosterone-secreting effects of angiotensin II at tissue receptor site. May induce more complete inhibition of renin-angiotensin system than ACE inhibitors and does not affect response to bradykinin (less likely to be associated with cough and angioedema).

Candesartan (Atacand)

Candesartan blocks vasoconstriction and aldosterone-secreting effects of angiotensin II. May induce more complete inhibition of renin-angiotensin system than ACE inhibitors, does not affect response to bradykinin, and is less likely to be associated with cough and angioedema. Use in patients unable to tolerate ACE inhibitors.

Valsartan (Diovan)

Produces direct antagonism of angiotensin II receptors. Displaces angiotensin II from AT1 receptor and may lower blood pressure by antagonizing AT1-induced vasoconstriction, aldosterone release, catecholamine release, arginine vasopressin release, water intake, and hypertrophic responses. Use in patients unable to tolerate ACE inhibitors.

Azilsartan (Edarbi)

Angiotensin II blocker; displaces angiotensin II from AT1 receptor and may lower blood pressure by antagonizing AT1-induced vasoconstriction, aldosterone release, catecholamine release, arginine vasopressin release, water absorption, and hypertrophic responses

May induce more complete inhibition of renin-angiotensin system compared with ACE inhibitors; does not affect response to bradykinin

Inhibits the pressor effects of an angiotensin II infusion in a dose-related manner

Eprosartan mesylate (Teveten)

Nonpeptide angiotensin II receptor antagonist that blocks vasoconstrictor and aldosterone-secreting effects of angiotensin II. May induce more complete inhibition of renin-angiotensin system than ACE inhibitors and does not affect response to bradykinin and is less likely to be associated with cough and angioedema.

For patients unable to tolerate ACE inhibitors.

Angiotensin II receptor blockers reduce blood pressure and proteinuria, protecting renal function, and delaying onset of end-stage renal disease.

Losartan (Cozaar)

Angiotensin II receptor antagonist that blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II. May induce a more complete inhibition of the renin-angiotensin system than ACE inhibitors, does not affect the response to bradykinin, and is less likely to be associated with cough and angioedema. For patients unable to tolerate ACE inhibitors.

Class Summary

The main objective of thrombolysis is to restore circulation through a previously occluded vessel by the rapid and complete removal of a pathologic intraluminal thrombus or embolus that has not been dissolved by the endogenous fibrinolytic system.

The first generation of fibrinolytic drugs (eg, streptokinase, urokinase, acetylated plasminogen streptokinase activator complexes [APSACs], reteplase, and novel plasminogen activator [nPA]) indiscriminately induced activation of circulating plasminogen and clot-associated plasminogen. First-generation drugs invariably elicited a systemic lytic state characterized by depletion of circulating fibrinogen, plasminogen, and hemostatic proteins and by marked elevation of concentrations of fibrinogen degradation products in plasma.

Second-generation drugs (eg, alteplase [t-PA], single-chain urokinase plasminogen activator), such as tenecteplase, preferentially activate plasminogen in the fibrin domain, rather than in the circulation, as with free plasminogen. Therefore, they have clot selectivity. Tenecteplase should be initiated as soon as possible in patients with STEMI; tenecteplase is administered as a single bolus, exhibiting a biphasic disposition from the plasma.

In optimal regimens, these agents induce clot lysis without inducing a systemic lytic state, they are less prone than nonselective agents to predispose the patient to hemorrhage necessitating transfusion, and they are effective in inducing recanalization in 80-90% of infarct-related arteries within 90 minutes. Therefore, t-PA recanalizes 75-80% of infarct-related arteries.

Alteplase, t-PA (Activase)

Alteplase (t-PA) is a fibrin-specific agent with a brief half-life of 5 minutes. Adjunctive therapy with IV heparin is necessary to maintain the patency of arteries recanalized by t-PA, especially during the first 24-48 hours.

Tenecteplase (TNKase)

Tenecteplase is a modified version of alteplase (t-PA) made by substituting 3 amino acids of alteplase. It can be given as a single bolus over a 5-second infusion, instead of 90 minutes with alteplase. Tenecteplase appears to cause less nonintracranial bleeding, but the risk of intracranial bleeding and stroke is similar to that of alteplase. Base the dose using patient weight. Initiate treatment as soon as possible after the onset of acute STEMI symptoms. Because tenecteplase contains no antibacterial preservatives, reconstitute immediately before use.

Class Summary

Pain control is essential to quality patient care. Analgesics ensure patient comfort, promote pulmonary toilet, and have sedating properties, which are beneficial for patients who experience pain.

Morphine sulfate (Duramorph, MS Contin, Kadian, Avinza)

Morphine sulfate is the drug of choice for narcotic analgesia due to its reliable and predictable effects, safety profile, and ease of reversibility with naloxone. Morphine sulfate is administered intravenously, may be dosed in a number of ways, and commonly is titrated until the desired effect is achieved.