Myocardial Infarction 

Updated: May 07, 2019
Author: A Maziar Zafari, MD, PhD, FACC, FAHA; Chief Editor: Eric H Yang, MD 

Overview

Practice Essentials

Myocardial infarction (MI) (ie, heart attack) is the irreversible death (necrosis) of heart muscle secondary to prolonged lack of oxygen supply (ischemia). Approximately 1.5 million cases of MI occur annually in the United States. See the images below.

Acute myocardial infarction, reperfusion type. In Acute myocardial infarction, reperfusion type. In this case, the infarct is diffusely hemorrhagic. There is a rupture track through the center of this posterior left ventricular transmural infarct. The mechanism of death was hemopericardium.
Acute anterior myocardial infarction. Acute anterior myocardial infarction.

See Are You Missing Subtle MI Clues on ECGs? Test Your Skills, a Critical Images slideshow, to help identify a variety of electrocardiographic abnormalities.

Signs and symptoms

Patients with typical MI may have the following symptoms in the days or even weeks preceding the event (although typical STEMI may occur suddenly, without warning):

  • Fatigue

  • Chest discomfort

  • Malaise

Typical chest pain in acute MI has the following characteristics:

  • Intense and unremitting for 30-60 minutes

  • Substernal, and often radiates up to the neck, shoulder, and jaw, and down the left arm

  • Usually described as a substernal pressure sensation that also may be characterized as squeezing, aching, burning, or even sharp

  • In some patients, the symptom is epigastric, with a feeling of indigestion or of fullness and gas

The patient’s vital signs may demonstrate the following in MI:

  • The patient’s heart rate is often increased (tachycardic) secondary to a high 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

  • 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 MI or severe left ventricular dysfunction, hypotension and cardiogenic shock can be seen

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

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

See Clinical Presentation for more detail.

Diagnosis

Laboratory studies

Laboratory tests used in the diagnosis of MI include the following:

  • Cardiac biomarkers/enzymes: The American College of Cardiology/American Heart Association (ACC/AHA) and the European Society of Cardiology (ESC) guidelines recommend that cardiac biomarkers should be measured at presentation in patients with suspected MI, and that the only biomarker that is recommended to be used for the diagnosis of acute MI at this time is cardiac troponin due to its superior sensitivity and accuracy.[1, 2, 3, 4]

  • Troponin levels: Troponin is a contractile protein that normally is not found in serum; it is released only when myocardial necrosis occurs

  • Complete blood cell count

  • Comprehensive metabolic panel

  • Lipid profile

Electrocardiography

The ECG is the most important tool in the initial evaluation and triage of patients in whom an acute coronary syndrome (ACS), such as MI, is suspected. It is confirmatory of the diagnosis in approximately 80% of cases.

Cardiac imaging

For individuals with highly probable or confirmed acute MI, coronary angiography can be used to definitively diagnose or rule out coronary artery disease.

See Workup for more detail.

Management

Prehospital care

For patients with chest pain, prehospital care includes the following:

  • Intravenous access, supplemental oxygen if SaO2 is less than 90%, pulse oximetry

  • Immediate administration of nonenteric-coated chewable aspirin

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

  • Telemetry and prehospital ECG, if available

Emergency department and inpatient care

Initial stabilization of patients with suspected MI and ongoing acute chest pain should include administration of sublingual nitroglycerin if patients have no contraindications to it.

The American Heart Association (AHA) recommends the initiation of beta blockers to all patients with STEMI (unless beta blockers are contraindicated).[1, 2]

If STEMI is present and the patient is within 90 minutes of a PCI-capable facility, the patient should undergo emergent coronary angiography and primary PCI. If the patient is longer than 120 minutes from a PCI-capable facility, fibrinolysis should be considered.[2]

Although patients presenting without ST-segment elevation (non-STE-ACS) are not candidates for immediate administration of thrombolytic agents, they should receive anti-ischemic therapy and may be candidates for PCI urgently or during admission.

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

  • Limit the extent of MI

  • Salvage jeopardized ischemic myocardium

  • Recanalize infarct-related arteries

See Treatment and Medication for more detail.

Background

Myocardial infarction (MI) usually results from an imbalance in oxygen supply and demand, which is most often caused by plaque rupture with thrombus formation in an epicardial coronary artery, resulting in an acute reduction of blood supply to a portion of the myocardium. (See Etiology for details.)

The electrocardiographic (ECG) results of an acute MI are seen below.

Acute inferior myocardial infarction. Acute inferior myocardial infarction.

Although the clinical presentation of a patient is a key component in the overall evaluation of the patient with MI, many events are either "silent" or are not clinically recognized by patients, families, and health care providers. (See Presentation.) The appearance of cardiac biomarkers in the circulation generally indicates myocardial necrosis and is a useful adjunct to diagnosis. (See Workup.)

MI 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 MI (NSTEMI)—collectively referred to as non–ST-segment acute coronary syndrome (NSTE ACS)—and ST-segment elevation MI (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 patients 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 depressions or T-wave morphological changes.

MI 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 MI, largely because they allow salvage of the myocardium when implemented early after the onset of ischemia. (See Treatment.)

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 salvage of substantial amounts of jeopardized ischemic myocardium is no longer likely. The opening of an infarct-related artery may improve ventricular function and collateral blood flow; prevent ventricular remodeling, as well as decrease infarct expansion, ventricular aneurysm formation, and left ventricular dilatation; and reduce late arrhythmia associated with ventricular aneurysms, and mortality.[5, 6, 7]

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 MI, along with a classification system and risk factors for cardiovascular death.[8]

(See Treatment for more details.)

Definitions

The third universal definition of myocardial infarction

Myocardial infarction (MI), commonly known as a heart attack, is defined pathologically as the irreversible death of myocardial cells caused by ischemia. Clinically, MI is a syndrome that can be recognized by a set of symptoms, chest pain being the hallmark of these symptoms in most cases, supported by biochemical laboratory changes, electrocardiographic (ECG) changes, or findings on imaging modalities able to detect myocardial injury and necrosis.

According to the third universal definition of MI, implemented by a joint task force from the European Society of Cardiology (ESC), American College of Cardiology (ACC) Foundation, American Heart Association (AHA), and the World Heart Federation (WHF), MI is diagnosed when either of the following two criteria are met.[9]

1. Detection of an increase or decrease in cardiac biomarker values (preferably using cardiac troponin [cTn]) with at least one value above the 99th percentile of the upper reference limit (URL) and with at least one of the following findings:

  • Symptoms of ischemia
  • New or presumed new significant ST-segment-T wave (ST-T) changes or new left bundle branch block (LBBB)
  • Development of pathologic Q waves on the ECG
  • Imaging evidence of new loss of viable myocardium or a new regional wall motion abnormality
  • Identification of an intracoronary thrombus by angiography or autopsy

2. Cardiac death with symptoms suggestive of myocardial ischemia and presumed new ischemic changes or injury or new BBB on ECG, but death occurred before cardiac biomarker levles were obtained, or before cardiac biomarker values would be increased.

Types of MI

The Joint ESC/ACCF/AHA/WHF Task Force further classified MI into 5 types on the basis of the underlying cause[7] :

  • Type 1 (spontaneous MI): Related to atherosclerotic plaque rupture, ulceration, fissuring, erosion, or dissection with intraluminal thrombus in one or more of the coronary arteries, leading to decreased myocardial blood flow or distal platelet emboli and thereby resulting in myocyte necrosis. The patient may or may not have underlying obstructive coronary artery disease (CAD).
  • Type 2 (MI secondary to an ischemic imbalance): MI consequent to increased oxygen demand or a decreased supply (eg, coronary endothelial dysfunction, coronary artery spasm, coronary artery embolus, tachyarryhthmias/bradyarrhythmias, anemia, respiratory failure, hypertension, or hypotension).
  • Type 3 (MI resulting in death when biomarker values are unavailable): Sudden, unexpected cardiac death before blood samples for biomarkers could be drawn or before their appearance in the circulation.
  • Type 4a (MI related to percutaneous coronary intervention [PCI]): Elevation of biomarker values (cTn is preferred) to more than 5 times the 99 th percentile of the URL in patients with normal baseline values (< 99 th percentile URL) or a rise of values over 20% if the baseline values are elevated but stable or falling. In addition, any of the following are required: (1) symptoms suggestive of myocardial ischemia; (2) new ischemic ECG changes or new BBB; (3) angiographic loss of patency of a major coronary artery or a side branch or persistent slow flow or no flow or embolization; or (4) demonstration of  the new loss of viable myocardium or new regional wall motion abnormality by cardiac imaging.
  • Type 4b (MI related to stent thrombosis): MI associated with stent thrombosis as detected by coronary angiography or autopsy in the setting of myocardial ischemia in combination with a rise and/or fall of cardiac biomarkers with at least one value above the 99 th percentile URL.
  • Type 5 (MI related to coronary artery bypass grafting [CABG]): Elevation of cardiac biomarker values more than 10 times the 99 th percentile URL in patients with normal baseline cTn values. In addition, either (1) new pathologic Q waves or new BBB, (2) angiographic-documented new graft or native coronary artery occlusion, or (3) evidence of new loss of viable myocardium or new regional wall motion abnormality by cardiac imaging is required.

Acute coronary syndrome

The term "acute coronary syndrome" (ACS) refers to a spectrum of conditions that occur due to acute myocardial ischemia and/or infarction as a result of an abrupt reduction in blood flow through the coronary artery circulation.

ACS is divided into two main categories, non–ST elevation (NSTE) ACS and ST-elevation MI (STEMI)

NSTE ACS

NSTE ACS is further divided into unstable angina (UA) and non–ST-elevation myocardial infraction (NSTEMI). These two conditions resemble each other very closely. UA is distinguished from NSTEMI by the absence of an elevation of cardiac biomarker levels.[1]

STEMI

The major discriminating feature of STEMI is the presence of symptoms of myocardial ischemia/injury along with persistent ECG ST-segment elevation in addition to the presence of cardiac biomarkers.[2]

Pathophysiology

Cellular effects of myocardial infarction (MI)

Myocardial injury and myocardial cell death

For the normal heart to continue to function and to steadily pump blood efficiently to meet the demands of the body, it needs to have a constant supply of oxygen and nutrients provided mainly by the coronary circulation. A condition called myocardial ischemia happens if blood supply to the myocardium does not meet the demand. If this imbalance persists, it triggers a cascade of cellular, inflammatory and biochemical events, leading eventually to the irreversible death of heart muscle cells, resulting in MI.

Evolution of MI and ventricular remodeling

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. Severe loss of the ability of the heart muscle cell to contract can be observed as early as within 60 seconds. Persistence of oxygen deprivation to the myocardium through the cessation of blood supply will lead to irreversible myocardial injury within 20 to 40 minutes and up to several hours, depending on several factors including the existing metabolic state of the body and presence of coronary collateral blood flow.[10]

Typical MI initially manifests as coagulation necrosis that is ultimately followed by a healing process characterized by formation of myocardial scarring, known as myocardial fibrosis. This mechanism allows significant architectural changes to the composition, shape and contractile function of the myocardium, especially in the left ventricle, which is the major contributor to the contractile function of the heart. Eventually the left ventricle dilates and changes to a more spherical shape, in a process known as ventricular remodeling. Despite being an irreversible process, ventricular remodeling is a regulated process, therefore, specific treatment strategies and agents should be used in acute MI management in order to reduce the occurrence and severity of ventricular remodeling.[11]

Reperfusion injury

In some occasions, restoration of blood flow to the damaged myocardium triggers further ischemic cellular damage, this paradoxical effect is known as reperfusion injury. This process involves a complex interaction between oxygen free radicals and intracellular calcium, leading to acceleration of myocardial damage and death, microvascular dysfunction and fatal arrhythmias. The role of nitric oxide (an endothelium-derived relaxing factor) as a cardioprotective agent against reperfusion injury, has been demonstrated, as nitric oxide works to inactivate oxygen free radicals, therefore, ameliorating the process of reperfusion injury.[12] Despite the improved understanding of the process of reperfusion injury, there are no specific therapies to prevent it.

Stunned and hibernating myocardium

Stunned myocardium is a condition of transient left ventricular dysfunction following an ischemic event to the myocardium. It occurs if coronary blood flow was impaired for a brief period of time (5 to 15 minutes). Usually, stunned myocardium persists for hours or days following the re-establishment of coronary blood flow.

However, prolonged exposure of the myocardium to an ischemic state, results in an impairment of its contractile function, which can be partial or complete, this is known as myocardial hibernation, and is reversible with revascularization.

Both myocardial stunning and hibernation occur because of loss of essential metabolites required for normal myocardial contractility, such as adenosine, which is needed for adenosine triphosphate (ATP)-dependent contraction.[13]

Plaque

The atheromatous plaque responsible for acute MI develops in a dynamic process in multiple stages. Starting with arterial intimal thickening, which consists of vascular smooth muscles with very minimal or no inflammatory cells, this process can be observed soon after birth. Subsequently, the formation of fibrous cap atheroma occurs, which has a lipid-rich necrotic core that is surrounded by fibrous tissue. Eventually, a thin-cap fibroatheroma develops, this is also known as a vulnerable plaque which is composed mainly of a large necrotic core separated from the vascular lumen by a thin fibrous cap that is infiltrated by inflammatory cells and is deficient of smooth muscle cells, making it vulnerable to rupture.[14, 15]

The process of acute coronary thrombosis leading to ACS involves the pathogenic mechanism of plaque rupture, and less frequently plaque erosion.

The Brasilia Heart Study Group indicates that changes in high-density lipoprotein (HDL) during an MI may alter the antiatherogenic function of HDL to transport lipids from arterial walls.[16]  The investigators noted a simultaneous decrease in lipid transfer to HDL and in the capacity of HDL to efflux cholesterol from cells occurs in the acute period after an MI.

In a nested case-control study that evaluated the associations of plasma metabolic markers with the risks of incident MI, ischemic stroke, and intracerebral hemorrhage, investigators found positive associations of lipoproteins and lipids with MI and ischemic stroke but not with intracerebral hemorrohage, as well as positive associations between triglyceride concentrations and MI.[17] Except for small HDL, there was also an inverse association of HDL particles with MI, and an inverse association of cholesterol in large HDL with MI and ischemic stroke. The study cohort included 912 patients with MI, 1146 with ischemic stroke, 1138 with intracerebral hemorrhage, and 1466 control subjects.[17]

Etiology

Atherosclerosis is the disease primarily responsible for most acute coronary syndrome (ACS) cases. Approximately 90% of myocardial infarctions (MIs) 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.[18]  A large body of evidence indicates that in numerous cases, culprit lesions are stenoses of less than 70% and are located proximally within the coronary tree.[19, 20] Coronary atherosclerosis is especially prominent near branching points of vessels.[21] 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[22] :

  • Smoking or other tobacco use

  • Hypercholesterolemia and hypertriglyceridemia, including inherited lipoprotein disorders

  • Dyslipidemia

  • Diabetes mellitus

  • Hypertension

  • Obesity (abdominal obesity)

  • Psychosocial stress

  • Sedentary lifestyle and/or lack of exercise

  • Reduced consumption of fruits and vegetables

  • Poor oral hygiene

  • Type A personality

  • Elevated homocysteine levels

  • Presence of peripheral vascular disease

MI can also occur for causes other than atherosclerosis. Nonatherosclerotic causes of MI include the following:

  • Coronary occlusion secondary to vasculitis

  • Ventricular hypertrophy (eg, left ventricular hypertrophy, hypertrophic cardiomyopathy)

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

  • 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

  • Respiratory infections, particularly influenza[23, 24]

In addition, MI can result from hypoxia due to carbon monoxide poisoning or acute pulmonary disorders.

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

Acute MI is rare in childhood and adolescence. Although adults acquire coronary artery disease from lifelong deposition of atheroma and plaque, which causes coronary artery spasm and thrombosis, children with acute MI usually have either an acute inflammatory condition of the coronary arteries or an anomalous origin of the left coronary artery. Intrauterine MI also does occur, often in association with coronary artery stenosis.[25]

Epidemiology

United States statistics

Coronary artery disease (CAD) is the leading cause of death in the United States; approximately 500,000-700,000 deaths related to CAD occur each year, making it the cause of death in an estimated one third of all deaths in the population for those older than 35 years.

Approximately 1.5 million cases of myocardial infarction (MI) occur annually in the United States; the yearly incidence rate is approximately 600 cases per 100,000 people. The proportion of patients diagnosed with non–ST-elevation MI (NSTEMI) compared with ST-elevation MI (STEMI) has progressively increased. Despite an impressive decline in age-adjusted death rates attributable to acute MI since the mid-1970s, the total number of MI-related deaths in the United States has not declined.[26]

The death rate related to acute MI is approximately three times higher in men than in women. It is more frequent in black patients compared to white patientss, an excess that disappears by age 75 years. Among the Hispanic population, coronary mortality is not as high as it is among black individuals and white persons.[27]

European statistics

CAD is also the number one cause of death in European countries.

In the European Union, death rates related to CAD dropped by almost 30% between the mid 1960s to the mid and late 1990s; however, within Eastern European countries, there was an increase in death rates related to acute MI in the early1990s, followed by a subsequent decline. In the Russian Federation, cardiovascular mortality remained the same.[28]  

Cardiovascular disease in other developed countries and in developing nations

An analysis of death certificates from the World Health Organization (WHO) database demonstrated that CAD mortality in Japan was significantly lower than in the United States and Europe, and it was further reduced by about 30% by the mid 1990s.[28]

In China, there has been a significant increase in mortality related to CAD, this is most likely attributed to the increase in cardiovascular disease risk factors, predominantly smoking and dyslipidemia.[29]

The incidence of CAD and related mortality is expected to rise dramatically in other developing countries including India, Latin America, the Middle East and Sub-Saharan Africa, with an estimated 80% increase, from approximately 9 million in 1990 to a projected 20 million by 2020.[30, 31]

It is believed that these international trends in the incidence of CAD and subsequent acute MI are largely related to consequences of social and economic changes in these countries, resulting in better healthcare access and increases in life expectancy, in addition to adoption of westernized diets, reduction in physical activity, and higher rates of smoking.

A major Canadian-led global study (INTERHEART trial) in 52 countries across Africa, Asia, Australia, Europe, the Middle East, and North and South America, has identified 9 easily measured risk factors (smoking, abnormal blood lipid levels, hypertension, diabetes, obesity, diet, physical activity, alcohol consumption, and psychosocial factors) that account for over 90% of the risk for acute MI.[22] The INTERHEART investigators found that these risk factors are the same in almost every geographic region and every racial/ethnic group worldwide, and they are consistent in men and women. The INTERHEART trial showed that smoking 1-5 cigarettes daily increased the risk of an acute MI by 40%, and the risk increased with the amount of tobacco smoked per day. It also concluded that all forms of tobacco, including filtered and nonfiltered cigarettes, pipes and cigars, and chewing tobacco, are harmful, and that abdominal obesity is a greater risk factor than body-mass index (BMI), indicating that measurement of waist-to-hip ratio could replace BMI as an indicator of obesity.[22, 31, 32]

Prognosis

Acute myocardial infarction (MI) is associated with a 30% mortality rate; about 50% 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 an MI are rehospitalized within 1 year of their index event.

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 (ST-elevation MI [STEMI] goals: patient arrival to fibrinolysis infusion within 30 minutes OR patient arrival to percutaneous coronary intervention [PCI] within 90 minutes)

  • Preserved left ventricular function

  • Short-term and long-term treatment with beta-blockers, aspirin, and angiotensin-converting enzyme (ACE) inhibitors

Poorer prognosis is associated with the following factors:

  • Advanced age

  • Diabetes mellitus

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

  • Elevated thrombolysis in MI (TIMI) risk score for unstable angina/non–ST elevation acute coronary syndrome (NSTE-ACS) (TIMI risk score includes 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 hours, aspirin use within prior week, and elevated cardiac enzyme levels)[1, 3, 33]

  • Delayed or unsuccessful reperfusion

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

  • Evidence of congestive heart failure (Killip classification ≥II)[34] or frank pulmonary edema (Killip classification ≥III)[35]

  • Elevated B-type natriuretic peptide (BNP) levels[36, 37, 38]

  • Elevated high sensitive C-reactive protein (hs-CRP), a nonspecific inflammatory marker[39]

  • Involvement of electrocardiograph (ECG) lead aVR[40, 41]

  • Depression

It has been shown that five baseline parameters at presentation of patients with acute MI account for over 90% of the prognostic predictors of 30-day mortality from acute MI. These parameters include age, systolic blood pressure on presentation, Killip classification, heart rate, and anatomic location of the MI.

Killip classification

The Killip classification is widely used in patients presenting with acute MI for the purpose of risk stratification, as follows[42] :

  • Killip class I includes individuals with no clinical signs of heart failure
  • Killip class II includes individuals with rales or crackles in the lungs, an S 3 gallop, and elevated jugular venous pressure
  • Killip class III describes individuals with frank acute pulmonary edema
  • Killip class IV describes individuals in cardiogenic shock or hypotension (measured as systolic blood pressure < 90 mmHg), and evidence of low cardiac output (oliguria, cyanosis, or impaired mental status).

Patient Education

Patients with active symptoms of acute coronary syndrome (ACS) should be instructed to call emergency services (eg, 911 in the United States), and they should be transported by emergency medical services personnel, not by themselves, family, or friends. Patients should be instructed to go 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 a caregiver should contact emergency services.[1]

Diet plays an important role in the development of coronary artery disease (CAD). Educate post–myocardial infarction (MI) patients about the role of a low-cholesterol and low-salt diet. A dietitian should see and evaluate all patients prior to discharge from the hospital. Additionally, emphasis on exercise training should be made, because current evidence demonstrates that cardiac rehabilitation after MI results in lower rates of recurrent cardiovascular events.[43]

All patients should be educated regarding the critical role of smoking in the development of CAD. Smoking cessation classes should be offered to help patients avoid smoking after their MI.

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.

 

Presentation

History

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

Patients with typical acute MI usually present with chest pain and may have prodromal symptoms of fatigue, chest discomfort, or malaise in the days preceding the event; alternatively, typical ST-elevation MI (STEMI) may occur suddenly without warning.

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

In some cases, patients do not recognize the chest pain, have an unusually high pain threshold, or have a disorder that impairs pain perception and results in a defective anginal warning system (eg, diabetes mellitus). In addition, some patients may have an altered mental status caused by medications 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.

MI occurs most often in the early morning hours. Mechanisms that may explain this circadian variation include the morning increase in sympathetic tone leading to increases in blood pressure, heart rate, coronary vascular tone, and myocardial contractility; the morning increase in blood viscosity, coagulability, and platelet aggregability; and the increased morning levels of serum cortisol and plasma catecholamines leading to sympathetic overactivity, thereby resulting in increased myocardial demand.[44, 45]

Initial rapid evaluation should include obtaining a brief history and performing a focused physical examination. Important elements of the history, such as characteristics of the pain and important associated symptoms, and past history of or risk factors for cardiovascular disease, are used to determine the likelihood that these symptoms represent acute coronary syndrome (ACS) and to predict the likelihood of clinical outcomes.[1]

Several risk assessment scores and clinical prediction algorithms are used to help identify patients with ACS at increased risk of adverse outcomes, such as TIMI (Thrombolysis In Myocardial Infarction) risk score, the GRACE (Global Registry of Acute Coronary Events) risk score, and the NCDR-ACTION (National Cardiovascular Data Registry-Acute Coronary Treatment and Intervention Outcomes Network) registry.[1, 3]

Investigators have also proposed a novel risk scoring system that may have the potential to predict cardiovascular death in patients with acute MI; the CHA2DS2-VASc-CF takes into account cigarette smoking and a family history of coronary artery disease as risk factors.[46]  In a retrospective study (2009-2016) comprising 4373 patients with acute MI (STEMI: n = 1427; NSTEMI: n = 2946) who presented to an emergency department and underwent cardiac catherization proceures, patients who experienced cardiac death in the follow-up period had significantly higher CHA2DS2-VASc and CHA2DS2-VASc-CF scores, and were more likely to have had major adverse cardiac events and hypertension, were older and current smokers, and have a family history of coronary artery disease; this group also had a significantly lower left ventricular ejection fraction and glomerular filtration rate than those who did not experience cardiovascular death. When the cutoff score for the CHA2DS2-VASc-CF was defined as greater than 3, there was a 78.4% sensitivity and 76.4% specificity for predicting long-term cardiovascular death.[46]

A high index of suspicion for MI should be maintained, 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 an MI or the need for coronary revascularization.

Other symptoms of myocardial infarction include the following:

  • Anxiety, commonly described as a sense of impending doom

  • Pain or discomfort in areas of the body, including the arms, left shoulder, back, neck, jaw, or stomach

  • Lightheadedness, with or without syncope

  • Cough

  • Nausea, with or without vomiting

  • Profuse sweating

  • Shortness of breath

  • Wheezing

  • Rapid or irregular heart rate

  • Fullness, indigestion, or choking feeling

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.

Physical Examination

Physical examination findings for myocardial infarction (MI) can vary; one patient may be comfortable in bed, with normal examination results, whereas another patient 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. 

Vital signs

Heart rate

The patient's heart rate is often increased (tachycardia 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.

Depressed heart rate may also be present in some cases. Bradyarrhythmias may be attributable to impaired function of the sinus node. An atrioventricular (AV) nodal block or infranodal block may also be present.

Unequal palpable pulses can be suggestive of the presence of aortic dissection, which commonly presents with chest pain radiating to the back, accompanied by a blood pressure difference of 15 mm Hg or greater between both arms and an aortic regurgitation murmur.

Blood pressure

In general, the patient's blood pressure is initially elevated (hypertension because of peripheral arterial vasoconstriction resulting from an adrenergic response to pain, anxiety, and ventricular dysfunction). However, it is not uncommon to have increased blood pressure as the precipitant of acute MI.

Alternatively, hypotension can also be seen. Usually this indicates either right ventricular MI or severe left ventricular dysfunction due to a large infarct area or impaired global cardiac contractility.

Respiratory rate

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

Temperature

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.[47, 48, 49]

Neck veins

In patients with acute inferior-wall MI with right ventricular involvement, distention of neck veins is commonly described as a sign of failure of the right ventricle. Impaired right ventricular function also leads to systemic venous hypertension, edema, and hepatomegaly.

Heart

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

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

A new 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 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 MIs. 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; it is produced through sliding contact of inflammation-roughened surfaces.

Chest

Rales or wheezes may be auscultated; these occur secondary to pulmonary venous hypertension, which is associated with extensive acute left ventricular MI. Unilateral or bilateral pleural effusions may produce egophony at the lung bases.

Abdomen

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

A pulsatile abdominal mass may suggest an abdominal aortic aneurysm.

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. 

 

DDx

Diagnostic Considerations

Epigastric or chest symptoms from myocardial ischemia may incorrectly be attributed to a gastrointestinal (GI) source. Often, this occurs despite the presence of dyspnea or diaphoresis, symptoms that are difficult to attribute to the GI system. Additionally, patients with myocardial ischemia may report relief or improvement with GI remedies (eg, antacids).

The discomfort of myocardial ischemia may also erroneously be attributed to a musculoskeletal etiology. Tenderness of the chest wall is reported in as many as 5% of patients who are diagnosed with myocardial infarction (MI). If no injury or event is defined that could have led to a soft-tissue injury, the clinician should be reluctant to render a diagnosis of musculoskeletal chest pain.

Younger patients are overly represented in cases of missed MI. Most likely this is because of the inherent bias that MI is a disease of middle-aged and older individuals. Each patient with chest symptoms should be approached as an individual who could have the disease.

Unfortunately, in a series of missed MI, failure to recognize ischemic changes was 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 of the electrocardiographic (ECG) tracing. 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.

Differential Diagnoses

 

Workup

Approach Considerations

The objectives of laboratory testing and imaging include the following:

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

  • To characterize the locus, nature (ST-elevation MI [STEMI] or non–ST-elevation MI [NSTEMI]), and extent of MI (ie, to estimate infarct size)

  • To detect recurrent ischemia or MI (extension of MI)

  • To detect early and late complications of MI

  • To estimate the patient's prognosis

The electrocardiogram (ECG) is the most important tool in the initial evaluation and triage of patients in whom an acute coronary syndrome (ACS) is suspected. 

Laboratory tests used in the diagnosis of myocardial infarction (MI) include the following:

  • Cardiac biomarkers/enzymes: The American College of Cardiology/American Heart Association (ACC/AHA) and the European Society of Cardiology (ESC) guidelines recommend cardiac troponin as the only cardiac biomarker that should be measured at presentation in patients with suspected MI, due to its superior sensitivity and accuracy. Troponin is a contractile protein that is not normally found in serum; it is released only when myocardial necrosis occurs.
  • Complete blood cell (CBC) count
  • Comprehensive metabolic panel
  • Lipid profile

Electrocardiography

The electrocardiogram (ECG) is the most important tool in the initial evaluation and triage of patients in whom an acute coronary syndrome (ACS) is suspected. Obtaining an ECG by emergency medical services (EMS) personnel at the site of first medical contact in patients with symptoms consistent with ST-elevation myocardial infarction (STEMI) not only confirms the diagnosis in more than 80% of cases, but also helps to detect life-threatening arrhythmias and allows early and prompt defibrillation therapy, if indicated.[2, 4]  

Expert medical societies and organizations including the American College of Cardiology (ACC), the American Heart Association (AHA), and the European Society of Cardiology (ESC) have implemented the importance of obtaining a 12-lead ECG in a timely fashion (≤10 mins of presentation) in their recommendations for management of ACS and STEMI, with interpretation by an experience physician.[1, 3]

Examples of ECGs showing MI are seen in the images below.

Acute anterior myocardial infarction. Acute anterior myocardial infarction.
Acute inferior myocardial infarction. Acute inferior myocardial infarction.
Acute posterolateral myocardial infarction. Acute posterolateral myocardial infarction.
The right-sided leads indicate ST-segment elevatio 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.

 

ECGs should be performed serially upon presentation to evaluate progression and assess changes with and without pain. 

Because the symptoms of acute MI can be subtle, an ECG 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.

Different ECG abnormalities

ECG is an effective tool to distinguish between acute MI and the myocardial ischemia that usually precedes it, as not all patients with myocardial ischemia will develop MI.

Transitioning from ischemia to infarction results in precise sequential electrical abnormalities captured on ECG. Moreover, these changes are localized, which helps in detection of the involved region of the myocardium in most cases.

In STEMI, 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 MI is difficult to differentiate from that seen in the presence of ischemia without MI or other unrelated conditions. ST-segment depression followed by T-wave inversion without the evolution of Q waves may result from non–ST-elevation MI (NSTEMI) or from subendocardial ischemia without MI.

High-probability ECG features of MI are the following:

  • ST-segment elevation greater than 1 mm in two anatomically contiguous leads
  • The presence of new Q waves

Intermediate-probability ECG features of MI are the following:

  • ST-segment depression
  • T-wave inversion
  • Other nonspecific ST-T wave abnormalities

Low-probability ECG features of MI are normal ECG findings. However, normal or nonspecific findings on ECGs do not exclude the possibility of MI.

Special attention should be made if there is diffuse ST depression in the precordial and extremity leads associated with more than 1 mm ST elevation in lead aVR, as this may indicate stenosis of the left main coronary artery or the proximal section of the left anterior descending coronary artery.[2, 4, 41]

Localization of the involved myocardium based on distribution of ECG abnormalities in MI is as follows:

  • Inferior wall - II, III, aVF

  • 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, and T-wave changes in V1, V8, and V9

True posterior-wall MIs may cause precordial ST depressions, 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.

Hyperacute (symmetrical and, often, but not necessarily pointed) T waves are frequently an early sign of MI at any locus.

The appearance of abnormalities in a large number of ECG leads often indicates extensive injury or concomitant pericarditis.

The characteristic ECG changes may be seen in conditions other than acute MI. For example, patients with previous MI and left ventricular aneurysm may have persistent ST elevations resulting from dyskinetic wall motion, rather than from acute myocardial injury. ST-segment changes may also be the result of misplaced precordial leads, early repolarization abnormalities, hypothermia (elevated J point or Osborne waves), or hypothyroidism.

False Q waves may be seen in septal leads in hypertrophic cardiomyopathy (HCM). They may also result from cardiac rotation.

Substantial T-wave inversion may be seen in left ventricular hypertrophy with secondary repolarization changes.

The QT segment may be prolonged because of ischemia or electrolyte disturbances.

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 MI.

Diffuse brain injuries and hemorrhagic stroke may also trigger changes in T waves, which are usually widespread and global, involving all leads.

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

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

To summarize, non-ischemic causes of ST-segment elevation include left ventricular hypertrophy, pericarditis, ventricular-paced rhythms, hypothermia, hyperkalemia and other electrolyte imbalances, and left ventricular aneurysm.

Cardiac Biomarkers

In the past, different cardiac biomarkers have been used to evaluate patients with suspected acute myocardial infarction (MI) (acute coronary syndrome [ACS] and ST-elevation MI [STEMI]). The cardiac-specific troponins I and T, creatine kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), and myoglobin have been used as surrogates for myocardial necrosis.

Cardiac troponin detection and quantification has improved dramatically over the years as advanced technology allows obtaining cardiac troponin assays running on automated platforms with a high degree of sensitivity. Although implementation of point-of-care testing (POCT) for cardiac biomarkers may seem to improve early diagnosis,[50, 51]  with an advantage of having a shorter turnaround time, this comes at the expense of substantial lower sensitivity and accuracy compared to results obtained from central laboratory testing.[52, 53, 54]

Serial measurement of cardiac troponins after the initial level is obtained at presentation, 3 to 6 hours after symptom onset, is recommended. If initial levels are negative, additional measurements beyond the 6-hour mark should be obtained.

The graph below demonstrates the timing of release of various cardiac biomarker peaks after the onset of MI.[55]

Timing of release of various cardiac biomarker pea Timing of release of various cardiac biomarker peaks after the onset of myocardial infarction

Cardiac Troponin

Troponin is a contractile protein that normally is not found in serum. It is released only when myocardial necrosis occurs. Of the three troponin subunits, two (troponin I and troponin T) are derived from the myocardium.

Highly sensitive assays can now detect cardiac troponin in patients with acute myocardial infarction (MI) with a high degree of certainty. This has led to the change in clinical practice guidelines to recommend relying solely on the results of sensitive or high-sensitive troponin I or troponin T assays for diagnostic and prognostication purposes in patients with symptoms suggestive of acute MI.[1, 56]  

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.

Measurement of troponin levels for patients with chest pain in the emergency setting has been studied extensively. Baseline measurement of troponin levels followed by serial measurements of troponin 3 hours afterward should be performed; both the absolute value of the troponin level as well as the degree of change in the troponin level should be considered. This has been associated with better performance in an accurate diagnosis of acute MI.[57, 58, 59]

For more information, see Cardiac Markers.

B-Type Natriuretic Peptide

B-type natriuretic peptide (BNP) is a 32-amino acid polypeptide secreted by the ventricles of the heart in response to excessive stretching of cardiomyocytes.

Measurement of BNP or N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) for the diagnosis of acute myocardial infarction (MI) is not recommended for diagnosis of MI, but these biomarkers have utility in risk stratification and prognostication of patients with acute MI who may have congestive heart failure.[38, 60]

Other Laboratory Studies

Complete blood cell count

Obtain a complete blood cell (CBC) count if myocardial infarction (MI) 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 MI, 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 (comprehensive metabolic panel)

In the setting of MI, closely monitor potassium and magnesium levels. The creatinine level is also needed, prior to cardiac catheterization and prior to initiating treatment with an angiotensin-converting enzyme (ACE) inhibitor. Blood glucose levels are important to measure, as many patients are first diagnosed with diabetes when they present with MI.

Although not routinely measured, 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 MI, 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 MI 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

A lipid profile may be helpful if obtained upon presentation, because levels can change after 12-24 hours of an acute illness. However, regardless of the lipid profile results, initiation of a high-intensity statin is recommended in all patients with acute coronary syndrome.

Cardiac Imaging

The role of imaging in the work-up of acute myocardial infarction (MI) is broad, but the procedures are primarily used to confirm or rule out coronary artery disease (CAD). Furthermore, imaging may help to define the anatomy and degree of myocardial perfusion abnormalities. In lower-risk individuals in whom acute coronary syndrome (ACS) is suspected and who do not have serial electrocardiographic (ECG) changes or positive serial cardiac biomarker findings, some form of stress testing may help to confirm the diagnosis and guide therapy.[1, 3]

For individuals with highly probable or confirmed ACS, consult with a cardiologist so that urgent coronary angiography can be performed; this procedure can be used to definitively diagnose or rule out CAD. 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 graft (CABG) surgery.

Multidetector computed tomography (MDCT) coronary angiography may be considered as an alternative to invasive angiography to exclude ACS when there is a low to intermediate likelihood of CAD and when cardiac troponin and/or ECG results are inconclusive.[61]  This imaging modality can be used in the emergency department for triage of patients with chest pain.[62]

The use of myocardial perfusion imaging (MPI) with single-photon emission CT (SPECT) or positron emission tomography (PET) scanning in the emergency department for low-risk patients has a low yield for detecting ischemia. Therefore, use of SPECT or PET scanning to diagnose MI in patients with negative serial troponin results and nondiagnostic ECGs is not routinely performed.[63]

Echocardiography is highly recommended and is required to evaluate ventricular function and wall-motion abnormalities. It is also used to identify pericardial effusion, ischemic mitral regurgitation, and cardiac tamponade that may complicate acute MI.

See Acute Myocardial Infarct Imaging for more detailed information.

 

Treatment

Approach Considerations

The first goal for healthcare professionals in management of acute myocardial infarction (MI) is to diagnose the condition in a very rapid manner.

As a general rule, initial therapy for acute MI 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 percutaneous coronary intervention (PCI), or coronary artery bypass graft (CABG) surgery.

Although the initial treatment of the different types of acute coronary syndrome (ACS) may appear to be similar, it is very important to distinguish whether the patient is having an ST-elevation MI (STEMI) or a non–STEMI (NSTEMI), because definitive therapies differ between these two types of MI. Particular considerations and differences involve the urgency of therapy and the degree of evidence regarding different pharmacologic options.

Over the last decade, inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising target to reduce residual cardiovascular disease risk. PCSK9 is a protein that binds to low-density lipoprotein (LDL) receptors (LDLR) to promote their degradation. Monoclonal antibodies inhibit PCSK9 and thus prevent LDLR degradation. This action will increase the number of LDLRs and subsequently increase the clearance of LDL, ultimately lowering LDL-C levels. 

In December 2017, the FDA approved the first PCSK9 inhibitor, evolocumab (Repatha), for the prevention of strokes, heart attacks, and coronary revascularizations.[64] The approval was based on data from the evolocumab cardiovascular outcomes study (FOURIER). In the FOURIER clinical trial, evolocumab demonstrated significant benefits for 27,564 patients with established cardiovascular disease. The study revealed that when used in addition to optimized statin therapy, evolocumab reduced the risk of heart attack by 27%, the risk of stroke by 21%, and the risk of coronary revascularization by 22%. In addition, evolocumab showed a statistically significant 15% reduction in the risk of the primary composite endpoint, which included hospitalization for unstable angina, coronary revascularization, heart attack, stroke, or cardiovascular death.[65]

Morbidity and mortality from MI 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 emergency department by private vehicle goes into cardiac arrest en route.[66]  In the United States, several studies have confirmed that patients with STEMI usually do not call 911, and only about 40% of patients with a confirmed coronary event used EMS.[67]

2017 American Heart Association/American College of Cardiology (AHA/ACC) clinical performance and quality measures for adults with STEMI and NSTEMI

Revised STEMI and NSTEMI measures[68, 69]

Statin use for patients with AMI (acute myocardial infarction)

Evaluation of LVEF (left ventricular ejection fraction)

P2Y12 receptor (clopidogrel, ticagrelor, prasugret) inhibitor prescribed at discharge. All 3 medications are inhibitors of the P2Y12 receptor and are recommended in addition to aspirin (as part of a dual antiplatelet regimen) to reduce recurrent ischemic events after AMI.

New STEMI/NSTEMI measures[68, 69]

Immediate angiography for resuscitated out-of-hospital cardiac arrest in STEMI patients.

Noninvasive stress testing before discharge in conservatively treated patients to detect inducible ischemia in medically treated STEMI and NSTEMI patients.

Early cardiac troponin measurement (within 6 hours of arrival).

Participation in regional or national acute myocardial infarction registry to help track and assess the outcomes, complications, and quality of care for patients with AMI.

Risk score stratification for NSTEMI patients to dictate the appropriate strategy (invasive versus ischemic-guided) and the timing of the strategy (early versus late invasive) in patients with NSTEMI.

Early invasive strategy (within 24 hours) in high-risk NSTEMI patients.

Therapeutic hypothermia for comatose STEMI patients with out-of-hospital cardiac arrest.

Aldosterone antagonist at discharge.

Inappropriate in-hospital use of nonsteroidal antiinflammatory drugs (NSAIDs) (caution against the use of these drugs after AMI).

Inappropriate prescription of prasugrel at discharge in patients with a history of prior stroke or transient ischemic attack (TIA) (caution against the use of prasugrel in patients with prior TIA/stroke, because of net clinical harm in these patients. The FDA also issued a black box warning on this.)

Inappropriate prescription of high-dose aspirin with ticagrelor at discharge (caution against the use of high-dose aspirin >100 mg among patients receiving ticagrelor. The FDA also issued a black box warning on this.)

Prehospital Care and Initial Management

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

Prehospital notification by emergency medical services (EMS) personnel should alert emergency department staff to the possibility of a patient with myocardial infarction (MI). EMS personnel should receive online medical advice for a patient with high-risk features; this allows for early and prompt delivery of medical treatment and, most importantly, facilitates the transportation of patients to facilities with the appropriate level of care.

Specific prehospital care includes the following:

  • Intravenous access, supplemental oxygen if the oxygen saturation (SaO2) is less than 90%, pulse oximetry

  • Immediate administration of nonenteric-coated chewable aspirin en route

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

  • Telemetry and prehospital electrocardiography (ECG), if available

Most deaths caused by MI occur early and are attributable to primary ventricular fibrillation (VF). Therefore, initial objectives are immediate ECG monitoring; electric cardioversion in cases of VF; and rapid transfer of the patient to facilitate prompt coronary assessment.

Prehospital integration of ECG interpretation has been shown to decrease "door-to-balloon time,” allow paramedics to bypass non–percutaneous coronary intervation (PCI)–capable hospitals in favor of PCI-capable facilities, and to expedite care by allowing an emergency department physician to activate the catheterization laboratory before the patient's arrival.

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 amiodarone and lidocaine); and support of cardiac output, systemic blood pressure, and respiration.

Prehospital fibrinolytic therapy by the administration of tissue-type plasminogen activator (t-PA), aspirin, and heparin may be given to patients with bona fide MI 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. Prehospital fibrinolytic therapy is not used widely in the United States due to the lack of resources to train EMS personnel or the lack of funding for necessary equipment. However, it is more widespread in some regions in Europe and the United Kingdom.

Emergency Department Care and In-Hospital Management

Triage and evaluation

Because acute coronary syndrome (ACS) is a spectrum of conditions, initial evaluation to establish a working diagnosis is crucial, as this will dictate management owing to some differences in management steps and timelines for each component of the ACS spectrum.

All patients presenting to the the emergency department with symptoms suggestive of acute myocardial infarction (MI) should be evaluated with a targeted history and focused physical examination (see Presentation). A 12-lead electrocardiogram (ECG) interpreted by an experienced physician should be completed within 10 minutes of arrival, in addition to establishing intravenous (IV) access.

Initial management

The initial management of the overall management plan for patients with acute MI has the following aims:

  • Restoration of the balance between oxygen supply and demand to prevent further ischemia
  • Pain relief
  • Prevention and treatment of complications

Oxygen

Continuous oxygen saturation monitoring by pulse oximetry is needed for all patients.

Supplemental oxygen by a mask or nasal cannula is indicated only for patients who are breathless, hypoxic (oxygen saturation < 90% or PaO2< 60 mm Hg[70] ), or who present with heart failure. The use of oxygen in patients with acute MI who don’t fall into one of the three above-mentioned categories remains uncertain, with some studies suggesting possible harm in such patients.[71]

Aspirin

All patients presenting with ACS should receive nonenteric-coated chewable aspirin in a dose of at least 162 to 325 mg, unless there is a clear history of aspirin allergy. Patients with aspirin intolerance still should receive aspirin at presentation.

Chewable aspirin is preferred, as this promotes rapid absorption into the bloodstream to achieve faster therapeutic levels.

Reduction of cardiac pain

Nitrates

Nitrates are potent vasodilators, and they act mainly to relax the venous system. Systemic venodilation results in reduction of venous blood return to the heart (ie, reducing the ventricular preload); this will lead to reduction of the workload of the heart, less oxygen demand, and reduction in ischemic pain. Nitrates are also the most commonly used agents to reduce cardiac chest pain related to ischemia via coronary vasodilation; however, their use is not associated with reduction in ACS-associated mortality.

Nitrates are usually given as a 0.4 mg dose in a sublingual tablet, followed by close observation of the effect on chest pain and the hemodynamic response. If the initial dose is well tolerated, further nitrates can be administered. The most common side effect of nitrates are hypotension and headache.

When chest pain persists or recurs, IV nitrates are indicated, usually started at a dose of 5 to 10 µg/min and gradually increased until relief of chest pain is achieved.

Nitrates should not be used in patients presenting with marked hypotension or bradycardia, or if there is suspicion of right ventricular infarction.

Special attention should be made in taking the history of whether concomitant use of phosphodiesterase (PDE) inhibitors (eg, sildenafil) has occurred within the last 24 to 72 hours, because this drug combination may lead to life-threatening hypotension.

Analgesia

Refractory or severe pain should be treated symptomatically with IV morphine.

The initial dose of morphine of 2 to 4 mg as an IV bolus can be given, with increments of 2 to 4 mg repeated every 5 to 10 minutes until the pain is relieved or intolerance is manifested by hypotension, vomiting, or depressed respiration. Should toxicity occur, a morphine antagonist such as naloxone is used for reversal. 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.

The use of other analgesic agents, such as nonsteroidal anti-inflammatory drugs (NSAIDs) should be avoided if at all possible, as the use of these agents has been associated with adverse cardiovascular events.[72]

ST-Elevation Myocardial Infarction

Management of ST-elevation myocardial infarction (MI) (STEMI) relies on two essential and key components: rapid recognition and timely reperfusion. Therefore, systems must be placed and implemented to prevent delay in management of patients who develop STEMI. Minimizing delays has been associated with improved overall outcomes as well as reduced mortality and long-term morbidity.[73, 74]  Current clinical practice guidelines have emphasized adopting institutional quality improvement measures to reduce total ischemic time, which is the principal determinant of outcome,[75, 76]  greatest emphasis is to be placed on the appropriate and timely use of some form of reperfusion therapy which is likely more important than the choice of therapy.[2]

Some factors that may lead to shortening total ischemic time include the following:

  • Prehospital electrocardiography (ECG) to diagnose STEMI to activate the percutaneous coronary intervention (PCI) team while the patient is en route to the hospital
  • Emergency department physicians activate the PCI team
  • A single call to a central page operator who activates the PCI team
  • The goal is set for the PCI team to arrive in the catheterization laboratory within 20 minutes after being paged
  • Timely data feedback and analysis are provided to members of the STEMI care team

Reperfusion

Early mechanical intervention (primary PCI) or pharmacologic reperfusion should be performed as soon as possible for patients with clinical presentation of STEMI within 12 hours of symptom onset and who have persistent ST-segment elevation or new or presumed new left bundle branch block (LBBB). In addition, it is reasonable to consider an early reperfusion strategy for patients presenting after more than 12 hours, provided there is clinical and/or ECG evidence of ongoing ischemia, with primary PCI being the preferred method in this population.

In the United States, only a minority of hospitals have the capability of performing primary PCI; therefore, a multifaceted community-wide approach that involves patient education, improvements in emergency medical services (EMS) and emergency department care, establishment of networks of STEMI-referral (non–PCI-capable) and STEMI-receiving (PCI-capable) hospitals, has been implemented to overcome this limitation.[77]

For patients presenting to a PCI-capable hospital, emergent coronary angiography and primary PCI should be accomplished within 90 minutes. For patients presenting to a non–PCI-capable hospital, if they cannot be transferred to a PCI-capable hospital within 120 minutes, it is very important to rapidly assess the following to reach a decision about administration of fibrinolytic therapy:

  1. The time from onset of symptoms
  2. The risk of complications related to STEMI
  3. The risk of bleeding with fibrinolysis therapy
  4. The presence of shock or severe heart failure
  5. The time required for transfer to a PCI-capable hospital

Even when interhospital transfer times are short, there may be relative advantages to a strategy of immediate fibrinolytic therapy versus any delay to primary PCI for eligible patients who present within the first 1 to 2 hours after symptom onset.[2]

Primary percutaneous intervention

PCI is defined as an emergent percutaneous coronary intervention in the setting of STEMI, without previous fibrinolytic treatment. It is the preferred reperfusion strategy in patients with STEMI, provided it can be performed expeditiously within clinical practice guidelines–mandated times and in high-volume centers with experienced interventional cardiology teams and skilled support staff.

PCI achieves superior reperfusion outcomes and is associated with less complications, death, and long-term complications of STEMI when compared to fibrinolytic therapy.[2, 4, 77, 78, 79]

Current guidelines strongly recommend performing primary PCI in patients presenting with symptoms of less than 12 hours' duration, or those who present with cardiogenic shock or who develop acute severe heart failure, irrespective of time of delay from onset of symptoms. Guidelines also recommend considering primary PCI for patients who present between 12 and 24 hours after onset of symptoms, provided there is ongoing clinical or ECG evidence of myocardial ischemia.

PCI of the noninfarct related artery (nonculprit artery) at the time of primary PCI of the culprit lesion is under active investigation. In a meta-analysis of 9 trials comprising 2991 patients with STEMI that compared complete multivessel PCI (revacularization of infarct-related and noninfarct-related arteries) to culprit-infarct-artery-only PCI, Vaidya et al noted their findings suggested complete revascularization is safe in patients with STEMI and multivessel disease.[80] Although complete vascularization appeared to be associated with lowered rates of major adverse cardiac events, cardiac death, and repeat revascularization in this population, no reduction in all-cause mortality and nonfatal MI was observed.[80]

This method of reperfusion entails performing emergent coronary angiography, after establishing arterial access, which can be achieved via the radial or femoral artery. After identifying the anatomy of the coronary circulation and determining the culprit vessel, coronary stents are placed to establish reperfusion.

In patients with STEMI, the evaluation of 70% ST-segment resolution following primary PCI appears to be a 5-year independent predictor of patient-oriented composite endpoint, particularly all-cause death and any revascularization.[81] The investigators suggested it may be used to identify those at high risk of very long-term cardiovascular events.

Drug-eluting stents (DES) or bare-metal stents (BMS) are used. However, if there are financial or social barriers that may limit patient compliance, an increased risk of bleeding, or an anticipated invasive or surgical procedure, the use of DES is not recommended.[2]

Placement of coronary stents requires dual antiplatelet therapy for an extended time period (see the subsection "Antiplatelet agents," below). The duration of therapy is dependent of the type of stent used.

Cardiac rupture is a major lethal complication of primary PCI for treatment of patients with STEMI. In a study comprising 1663 STEMI patients who underwent PCI of whom 33 (1.98%) developed cardiac rupture, investigators noted that the SYNTAX  (Synergy between percutaneous coronary intervention with Taxus and Cardiac Surgery) Score II (SSII), which is used to assess anatomic and clinical risk in patients with stable coronary artery disease, is an independent predictor for cardiac rupture, which in itself has a poor prognosis.[82]  Increasing SSII tertiles were noted to be associated with a gradual rise in cardiac rupture occurrence.

Fibrinolysis

Fibrinolysis is an important reperfusion strategy, particularly in settings where primary PCI cannot be offered to STEMI patients within the recommended timelines. The benefit of fibrinolytic therapy in patients with STEMI is well established, with the largest benefit seen when administered early (within 12 hours after symptomatic onset) and in patients with the highest cardiovascular risk, including patients older than 75 years.[83, 84]

Fibrinolytic therapy may not be beneficial in patients who present more than 12 hours after symptom onset, although current practice guidelines recommend consideration of fibrinolysis in symptomatic patients with a large area of myocardium at risk (based on ECG or cardiovascular imaging) or hemodynamic instability if PCI is unavailable. See absolute and relative contraindications to fibrinolytic therapy in table 1, below.

Table 1. Absolute and Relative Contraindications to Fibrinolytic Therapy in Patients with STEMI (Open Table in a new window)

Absolute Contraindications Relative Contraindications
  • Any prior intracranial hemorrhage
  • Known structural cerebral vascular lesion
  • Known intracranial neoplasm (primary or metastatic)
  • Ischemic stroke within the past 3 months (except for acute stroke within 4.5 hours)
  • Suspected aortic dissection
  • Active bleeding or bleeding diathesis (excluding menses)
  • Significant closed-head or facial trauma within 3 months
  • Intracranial or intraspinal surgery within 2 months
  • Severe uncontrolled hypertension (unresponsive to emergency therapy)
  • For streptokinase (no longer marketed in the US): Prior treatment within previous 6 months
  • History of chronic, severe, poorly controlled hypertension
  • Systolic pressure >180 mm Hg or diastolic pressure >110 mm Hg
  • History of prior ischemic stroke >3 months
  • Dementia
  • Known intracranial pathology not covered in absolute contraindications
  • Traumatic or prolonged CPR (>10 minutes)
  • Recent (within 2-4 weeks) internal bleeding
  • Noncompressible vascular punctures
  • Pregnancy
  • Active peptic ulcer disease
  • Current use of anticoagulants: The higher the INR, the higher the risk of bleeding
  • For streptokinase (no longer marketed in the US): Prior exposure (>5 days previously) or prior allergic reaction to these agents

CPR = cardiopulmonary resuscitation; INR = international normalized ratio; STEMI = ST-elevation myocardial infarction; US = United States of America.

 

Table modified from 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.[2]

Fibrinolytic therapy is associated with an excess of strokes, mainly due to cerebral hemorrhage, which is more commonly seen in patients with advanced age, lower weight, female sex, prior cerebrovascular disease, and hypertension on admission.[85]

Different fibrinolytic agents are available, and table 2, below, lists different fibrinolytic agents with some of their key characteristics. In general, fibrin-specific agents are preferred when available. Note: Streptokinase is no longer marketed in the United States.

Table 2. Fibrinolytic Agents Used in Management of STEMI. (Open Table in a new window)

Fibrinolytic Agent

Dose

Fibrin Specificity

Antigenic

Patency Rate

Non-fibrin specific

 

 

 

 

Streptokinase (no longer marketed in the US)

1.5 million units IV given over 30–60 min

No

Yes

60%–68%

Fibrin specific

 

 

 

 

Tenecteplase

(TNK-tPA)

30 mg for weight < 60 kg

35 mg for 60–69 kg

40 mg for 70–79 kg

45 mg for 80–89 kg

50 mg for >90 kg

++++

No

85%

Reteplase (rPA)

10-U IV boluses given 30 min apart

++

No

84%

Alteplase (tPA)

Bolus 15 mg followed by infusion 0.75 mg/kg for 30 min (maximum 50 mg), then 0.5 mg/kg (maximum 35 mg) over the next 60 min; total dose not to exceed 100 mg.

++

No

73%-84%

IV = intravenous; rPA = recombinant human tissue plasminogen activator; STEMI = ST-elevation myocardial infarction; tPA = tissue plasminogen activator; US = United States of America.

 

Table modified from 2013 ACCF/AHA guidelines for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.[2]

 

Coronary artery bypass grafting (CABG)

Despite great improvement of intraoperative myocardial preservation, CABG has a limited role in the acute management of STEMI. However, CABG remains indicated for cardiogenic shock, failed PCI, high-risk anatomy, surgical repair of a mechanical complication of STEMI (eg, ventricular septal rupture, free-wall rupture, or severe mitral regurgitation from papillary muscle dysfunction or rupture). CABG is also the preferred revascularization strategy for patients with unprotected left main disease, but PCI with DES is a reasonable alternative treatment option in those with favorable anatomy and high surgical risk.[86]

Anticoagulation

Anticoagulant agents are an important adjunctive therapy for reperfusion therapy regardless of the strategy chosen (ie, whether it is primary PCI or fibrinolysis therapy). Different anticoagulation agents are available; the utility of each agent depends on the clinical context, taking into account the method of reperfusion.

For primary PCI, unfractionated heparin (UFH), bivalirudin,[2, 4]  and low molecular weight heparin (LMWH) (eg, enoxaparin[4] ) are the available options. Fondaparinux is not used in this setting because of the increased risk of catheter thrombosis.[87]

In patients receiving fibrinolytic therapy, anticoagulation should be given until revascularization is performed; if reperfusion is not feasible anticoagulants should be given for at least 48 hours or for the duration of hospital stay up to 8 days.[4]  UFH or LMWH may be used, with LMWH (enoxaparin) being preferred.[88, 89, 90]  Use caution with the administration of enoxaparin in patients older than 75 years as well as those with impaired renal function, because the use of enoxaparin is associated with a higher risk of intracranial bleeding. Bivalirudin may be used for patients who develop or have a history of heparin-induced thrombocytopenia (HIT) and require anticoagulation.[91]

Antiplatelet agents

All patients with STEMI should receive an empiric loading dose of aspirin (150.5 to 325 mg) as early as possible and prior to reperfusion, regardless of the reperfusion method. A lifelong maintenance dose of (75 to 81 mg) daily should be prescribed to all patients after STEMI.

Other antiplatelet agents used for dual antiplatelet therapy are the P2Y12 receptor inhibitors (eg, clopidogrel, ticagrelor, prasugrel); a loading dose of these agents is given before or at the time of reperfusion and an extended duration maintenance dose is administered thereafter, depending on the method of reperfusion.

For patients undergoing primary PCI, a loading dose of 600 mg of clopidogrel, 180 mg of ticagrelor, or 60 mg of prasugrel should be given as early as possible or at the time of primary PCI. A maintenance dose of P2Y12 receptor inhibitors should be continued for at least 1 year for patients who receive a stent, either a BMS or a DES. A daily dose of 75 mg clopidogrel, 90 mg ticagrelor (twice daily), or 10 mg prasugrel is recommended. It is reasonable to discontinue P2Y12 receptor inhibitor agents prior to 1 year for patients who receive a BMS if there is evidence of increased bleeding.

Introducing ticagrelor after myocardial infarction in patients with previous ischemic stroke is associated with lower rates of recurrent ischemic stroke, without an increase in intracranial bleeding.[92]

The use of prasugrel is not recommended for patients with a history of stroke or transient ischemic attack (TIA).[93, 94, 95]

For patients who receive fibrinolytic therapy, a loading dose of clopidogrel 300 mg followed by a daily maintenance dose of 75 mg should be given, preferably for 1 year or a minimum of 14 days. The use of other P2Y12 receptor inhibitor agents in patients treated with fibrinolysis has not been prospectively studied.[2]

Other antiplatelet agents that may be used in STEMI management are the intravenous (IV) glycoprotein (GP) IIb/IIIa receptor antagonists. The adjunctive use of GP IIb/IIIa agents at the time of PCI can be considered on an individual basis for a large thrombus burden or inadequate P2Y12 receptor antagonist loading. For patients receiving bivalirudin as the primary anticoagulant, routine adjunctive use of GP IIb/IIIa inhibitors is not recommended but may be considered in selected cases.[2, 4]

Non-ST-Elevation (NSTE) ACS

Key points in the management of patients with non–ST-elevation acute coronary syndrome (NSTE-ACS) (unstable angina and non-STE myocardial infarction [NSTEMI]) is early evaluation and assessment of hemodynamic and electrical stability, estimatation of the overall risk in these patients, and guidance of therapy.

There are two alternative management strategies, either an early invasive strategy with angiography, with intent for revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), or a conservative strategy with initial medical therapy and noninvasive cardiovascular imaging. Regardless of the strategy, both entail aggressive utility of medications such as anticoagulants, antiplatelet agents, beta blockers, statins, and possible use of angiotensin-converting enzyme (ACE) inhibitors for appropriate patient populations.

Patients with refractory angina, clinical evidence of heart failure, or hemodynamic or electrical instability who do not have serious comorbidities or contraindications to angiography/PCI should undergo an early invasive strategy.

An immediate early invasive strategy is also recommended for patient who are stable but at a high risk for clinical events. It is reasonable to consider an early invasive strategy within 24 hours of admission in patients with intermediate/high risk. For patients who fall outside this category, a delayed invasive strategy within 25 to 72 hours of admission versus a conservative (ischemia-guided) strategy may be considered.[1]

Beta blockers

Beta blockers work by reduction of oxygen consumption of the myocardium by lowering the heart rate, blood pressure, and myocardial contractility. They also play an important role in reduction of reinfarction and complex ventricular arrhythmias.[31, 96] These agents are recommended to be given orally within the first 24 hours, preferably using one of the three drugs proven to reduce mortality in heart failure patients: metoprolol, carvedilol, or bisoprolol.

Beta blockers should not be given intravenously in patients with evidence of low cardiac output state (heart rate >110 beats/min or systolic blood pressure < 100 mmHg), and used with caution in elderly patients or in individuals with an unknown left ventricular ejection fraction.[96]  These agents should also not be given to patients who have a contraindication to beta blockers (eg, first-degree heart block with a PR interval >240 ms, second- or third-degree heart block without a cardiac pacemaker, recent cocaine use, severe/advanced active reactive airway disease).

In patients with chronic obstructive lung disease or chronic asthma, beta-1 selective beta blockers are preferred and should be initiated at low doses.

Calcium channel blockers

Non-dihydropyridine calcium channel blockers (eg, verapamil or diltiazem) should be given for recurrent myocardial ischemia only if there are contraindications to using beta blockers. Similar to beta blockers, use of non-dihydropyridine calcium channel blockers can also increase the likelihood of developing cardiogenic shock, thus, similar caution should be used when considering the use of these drugs.[96]

Avoid short-acting nifedipine in patients who are not receiving beta blockers, as this may result in increased mortality in patients with ACS.[96]

Antiplatelet agents

Aspirin

Nonenteric-coated chewable aspirin 150 to 325 mg should be given to all patients with NSTE-ACS as soon as possible after presentation.

A maintenance dose of aspirin 75-100 mg daily should be continued indefinitely.[1, 3]

Some clinical data suggest that maintenance dose of aspirin higher than 160 mg daily is associated with increased risk of bleeding with no clear improvement in outcomes.[97, 98]

P2Y12 receptor inhibitors

The use of P2Y12 receptor inhibitors in addition to aspirin has resulted in better outcomes, with a reduction of the incidence of cardiovascular death, MI, and stroke. The three P2Y12 receptor inhibitors most commonly used in the treatment of NSTE-ACS are described in this section, as follows:

  • Clopidogrel
  • Ticagrelor
  • Prasugrel

All three agents are given with an initial loading dose, followed by a daily maintenance dose up to 12 months for all patients treated for NSTE ACS with either early invasive or conservative strategies.

With the wider use of new generation drug-eluting stents (DES), a shorter duration of P2Y12 receptor inhibitors of 3-6 months can be considered in patients who are at high bleeding risk.

Clopidogrel

A oading dose of clopidogrel 300-600 mg is recommended, followed by a maintenance dose of 75 mg daily.

Extrapolated results from the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial demonstrated that clopidogrel can be used in patients with NSTE-ACS who are intolerant to aspirin.[99]

Ticagrelor

Ticagrelor is a reversible inhibitor of the P2Y12 receptor that has a more rapid onset of action and a shorter half-life than clopidogrel; therefore, it is administered twice daily for maintenance. A loading dose of ticagrelor 180 mg is recommended, followed by a maintenance dose of 90 mg twice daily. 

The Platelet Inhibition and Patient Outcomes (PLATO) trial compared clopidogrel to ticagrelor in patients with NSTE-ACS and concluded that patients receiving ticagrelor had lower events of MI, stroke, and overall mortality.[100]

A unique side effect observed in patients taking ticagrelor is dyspnea, but this is rarely severe enough to cause termination of treatment.[101]

Ticagrelor should not be used concomitantly with higher doses of aspirin (>100 mg daily).

Prasugrel

A loading dose of prasugrel 60 mg is recommended, followed by a maintenance dose of 10 mg daily.

Because of the unique metabolic conversion pathways of prasugrel, it has a more rapid and more consistent platelet inhibition than clopidogrel, which was demonstrated in the Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel–Thrombolysis in Myocardial Infarction (TRITON–TIMI) 38 trial. However, there was a concern of an increased bleeding risk in individuals treated with prasugrel.[93, 94, 95] Therefore, major contraindication to the use of prasugrel are a previous history of stroke or transient ischemic attack (TIA), age over 75 years, and low body weight (< 60 kg).[93]

Current clinical practice guidelines have different recommendations with regard to the use of prasugrel upfront in patients with NSTE-ACS. The American College of Cardiology/American Heart Association (ACC/AHA) guidelines do not recommend the use of prasugrel in this setting; however, its use can be considered for those undergoing PCI.[96]  The ESC guidelines, however, recommend the use of prasugrel upfront in patients treated for NSTE-ACS—provided there is no contraindication to its use.[3]

Glycoprotein (GP) IIb/IIIa receptor inhibitors

The Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial[102] and the Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis (RESTORE) trial[103] demonstrated the efficacy of these agents in the treatment of NSTE-ACS.

The preferred GP IIb/IIIa receptor inhibitors are eptifibatide or tirofiban. Patients undergoing an early invasive strategy who received dual antiplatelet therapy with high-risk features are considered candidates to receive either of these two agents.[1, 3]

However, GP IIb/IIIa agents are associated with an increased risk of bleeding complications, and most of the clinical trials studying these drugs were completed prior to the release of the P2Y12 receptor inhibitors. Thus, their use in NSTE-ACS is limited currently.

Anticoagulant therapy

Anticoagulant agents are recommended to be given to all patients with NSTE-ACS, regardless of the initial treatment strategy, in addition to antiplatelet therapy. The following agents may be considered as treatment options from this group of medications.

Unfractionated heparin (UH)

An initial loading dose of 60 IU/kg (maximum 4,000 IU) with an initial infusion of 12 IU/kg per hour (maximum 1,000 IU/h) adjusted per activated partial thromboplastin time (PTT) is recommended to maintain therapeutic anticoagulation according to the specific hospital protocol. This regimen is continued for 48 hours or until PCI is performed.

A major disadvantage of the use of unfractionated heparin is the large interindividual variability and narrow therapeutic window.

Low molecular weight heparin (LMWH)

Enoxaparin is given at a dose of 1 mg/kg subcutaneously (SC) every 12 hours. It should be continued for the duration of hospitalization or until PCI is performed. A dose reduction is required for patients with impaired kidney function.

Enoxaparin results in a more predictable and efficient anticoagulation compared to unfractionated heparin, leading to reduction in recurrent MI events[104, 105] ; however, there is possibly a higher bleeding risk in patients undergoing PCI.[106] These findings were demonstrated in the Efficacy and Safety of Subcutaneous Enoxaparin in Non–Q wave Coronary Events (ESSENCE) trial.[104, 105, 106]

Bivalirudin

Bivalirudin is direct thrombin inhibitor that is given as 0.1 mg/kg loading dose, followed by 0.25 mg/kg per hour only in patients managed with an early invasive strategy. This regimen is continued until diagnostic angiography or PCI.[107] In the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) Trial, the efficacy of bivalirudin was noninferior to the use of heparin plus GP IIb/IIIa.[108]

Fondaparinux

Fondaparinux is a selective factor X inhibitor. This agent is given as a once-daily SC injection of 2.5 mg, which is continued for the duration of hospitalization or until PCI is performed.

Note that fondarparinux is contraindicated in patients with impaired kidney function. In addition, in patients undergoing PCI, administer another anticoagulant agent (eg, unfractionated heparin or bivalirudin), as fondaparinux is associated with a higher risk of catheter thrombosis; this was demonstrated in the Fifth Organization to Assess Strategies in Ischemic Syndromes (OASIS-5) trial.[87, 109, 110]

Additional Aspects of Management and Late Hospital Care

After the initial management and stabilization of the patient in the early and critical phase of acute myocardial infarction (MI), the goals of care for these patients is to restore normal activities, prevent long-term complications, as well as aggressively modify lifestyle and risk factors. This multifaceted goal is achieved with the implementation of important key elements, including the use of cardioprotective medications and cardiac rehabilitation, as well as physical activity, diet, and patient education.

Cardioprotective medications

Inhibitors of the renin-angiotensin-aldosterone (RAA) system

Initiate angiotensin-converting enzyme (ACE) inhibitors and continue administration indefinitely in all patients with a left ventricular ejection fraction that is less than 40% and in those with hypertension, diabetes mellitus, or stable chronic kidney disease, unless contraindicated.[111, 112]

Angiotensin-receptor blockers (ARBs) are recommended in patients who are intolerant of ACE inhibitors.[113]

Aldosterone blockers are recommended in addition to beta blockers and ACE inhibitors in patient who have had an MI with a reduced left ventricular ejection fraction of less than 40%, provided they have no renal impairment and have normal blood potassium levels (< 5 mEq/L). This was emphasized in the Eplerenone Post-acute myocardial infarction Heart failure Efficacy and Survival Study (EPHESUS).[114]  

Beta blockers

After an MI, all patients should be maintained on a beta blocker. Current clinical practice guidelines recommend use of one of three beta blocker agents proven to reduce mortality in patients with heart failure: metoprolol, carvedilol, or bisoprolol.

See the discussion on beta blockers in the previous section, Non-ST-Elevation (NSTE) ACS.

Statins

All patients with an acute MI should be started on high-potency statin therapy and continued indefinitely.

Current clinical practice guidelines, high potency statins such as atorvastatin 40 mg or 80 mg, or rosuvastatin 20 mg are recommended.[1, 2, 115]

The Effects of Atorvastatin on Early Recurrent Ischemic Events In Acute Coronary Syndromes (MIRACL) trial[116] and the Atorvastatin for Reduction of Myocardial Damage During Angioplasty-Acute Coronary Syndromes (ARMYDA-ACS) trial[117] demonstrated a reduction in mortality rates in patients who received high-potency statins after acute MI as compared to placebo.

Lifestyle modifications and cardiac rehabilitation

Much emphasis has been placed on postdischarge care for patients after MI.

Several lifestyle modifications have been strongly linked to a reduction in recurrent MI and prevention of further progression of cardiovascular disease. These modification include dietary changes that adopt a low-fat and low-salt diet with dietary counseling, smoking cessation, up-to-date vaccination, and an increase in physical activity and exercise.

Referral to a well-structured cardiac rehabilitation program after MI should be considered for all patients, as this will promote patient compliance with the medical regimen and enhance lifestyle changes. In addition, aerobic exercise training within a cardiac rehabilitation program should be offered to patients after MI, with the need for an evaluation of both exercise capacity and exercise-associated risk.

The recommended frequency of regular exercise training is three or more times a week, for at least 30 minutes per session.[1, 2, 118]

2019 ACC/AHA primary CVD prevention recommendations

The American College of Cardiology (ACC) and the American Heart Association (AHA) published recommendations on the primary prevention of cardiovascular disease (CVD) in March 2019.[119, 120] Ten key messages and a few recommendations from the guidelines are summarized below, including an emphasis on lifestyle choices/modifications and a major shift away from the broad use of aspirin in primary prevention.

◊ Key messages

A healthy lifestyle over a lifetime is the most important way to prevent atherosclerotic vascular disease, heart failure, and atrial fibrillation.

A team-based care approach is an effective strategy for CVD prevention. Clinicians should evaluate the social determinants of health that affect individuals to inform treatment decisions.

Adults aged 40-75 years being evaluated for CVD prevention should undergo 10-year atherosclerotic CVD (ASCVD) risk estimation and have a clinician–patient risk discussion before being started on pharmacotherapy (eg, antihypertensive therapy, a statin, or aspirin). The presence or absence of additional risk factors and/or the use of coronary artery calcium (CAC) scanning can help guide decisions about preventive interventions in select individuals.

All adults should consume a healthy diet that emphasizes consumption of vegetables, fruits, nuts, whole grains, lean vegetable or animal protein, and fish, and minimizes the intake of trans fats, processed meats, refined carbohydrates, and sweetened beverages. In the setting of overweight and obesity, counseling and caloric restriction are recommended to achieve and maintain weight loss.

Adults, including those with type 2 diabetes mellitus (T2DM), should engage in at least 150 minutes per week of accumulated moderate-intensity physical activity or 75 minutes per week of vigorous-intensity physical activity.

For adults with T2DM, lifestyle changes (eg, improving dietary habits, achieving exercise recommendations) are crucial. If medication is indicated, metformin is first-line therapy, followed by consideration of a sodium-glucose cotransporter 2 inhibitor (SGLT2) or a glucagon-like peptide-1 receptor agonist (GLP-1).

At every healthcare visit, assess all adults for tobacco use. Assist tobacco users and strongly advise them to quit.

Aspirin should be used infrequently in the routine primary prevention of ASCVD because of a lack of net benefit.

Statin therapy is first-line treatment for the primary prevention of ASCVD in patients with elevated low-density lipoprotein cholesterol (LDL-C) levels (≥190 mg/dL), those with diabetes mellitus who are aged 40-75 years, and those determined to be at sufficient ASCVD risk after a clinician-patient risk discussion.

Nonpharmacologic interventions are recommended for all adults with elevated blood pressure or hypertension. When pharmacologic therapy is required, target the blood pressure to generally be below 130/80 mmHg.

◊ Select recommendations

For adults aged 40-75 years, routinely assess traditional CV risk factors and calculate their 10-year ASCVD risk with the pooled cohort equations (PCE). For those aged 20-39 years, it is reasonable to assess traditional ASCVD risk factors at least every 4-6 years.

In adults at borderline risk (5% to < 7.5% 10-year ASCVD risk) or intermediate risk (≥7.5% to < 20% 10-year ASCVD risk), using additional risk-enhancing factors is reasonable to guide decisions about preventive interventions (eg, statin therapy).

In adults at intermediate risk (≥7.5% to < 20% 10-year ASCVD risk) or selected adults at borderline risk (5% to < 7.5% 10-year ASCVD risk), if risk-based decisions for preventive interventions (eg, statin therapy) remain uncertain, measuring a CAC score to guide the clinician-patient risk discussion is reasonable, as follows:

  • CAC = 0: Withholding statin therapy is reasonable; reassess in 5-10 years if higher risk conditions are absent (eg, diabetes, family history of premature coronary heart disease, tobacco use).

  • CAC = 1-99: Initiating statin therapy is reasonable for those aged 55 years or older.

  • CAC is ≥100, or is in ≥75th percentile: Initiating statin therapy is reasonable.

For adults aged 20-39 years and for those aged 40-59 years whose 10-year ASCVD risk is below 7.5%, consider estimating their lifetime or 30-year ASCVD risk.

In adults at intermediate risk (≥7.5% to < 20% 10-year ASCVD risk):

  • If statin therapy is decided upon, use a moderate-intensity agent.

  • Reduce LDL-C levels by ≥30%; for optimal ASCVD risk reduction, particularly in high-risk patients (≥20% 10-year ASCVD risk), reduce LDL-C levels by ≥50%.

  • In the setting of risk-enhancing factors, initiating or intensifying statin therapy is favored.

In diabetic adults aged 40-75 years, regardless of the estimated 10-year ASCVD risk, moderate-intensity statin therapy is indicated. High-intensity statin therapy is reasonable for diabetic adults with multiple ASCVD risk factors to reduce LDL-C levels by 50% or more.

The maximally tolerated statin therapy is recommended in patients aged 20-75 years with LDL-C levels of 190 mg/dL (≥4.9 mmol/L) or higher.

Blood pressure (BP)-lowering agents are recommended for the following patients:

  • Adults with an estimated 10-year ASCVD risk of ≥10% and an average BP of ≥130/80 mmHg (for primary CVD prevention)

  • Adults with an estimated 10-year ASCVD risk < 10% and a BP of ≥140/90 mmHg

Low-dose aspirin (75-100 mg orally daily) guidance includes the following:

  • Consider for primary ASCVD prevention in select adults aged 40-70 years who have higher ASCVD risk but not an increased bleeding risk.

  • Do not routinely administer for primary ASCVD prevention in adults >70 years as well as in adults of any age who have a higher bleeding risk.

Special considerations for elderly patients

Elderly patients should be treated aggressively. However, this patient population with MI is at an increased risk for developing complications, such as a greater 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.

Complications

Complications of myocardial infarction (MI) include arrhythmic complications, mechanical complications, left ventricular aneurysm formation, ventricular septal rupture, associated right ventricular infarction, ventricular pseudoaneurysm, and other issues. See Complications of Myocardial Infarction.

Arrhythmic complications

Cardiac arrhythmias are not uncommon during and immediately after an acute MI. The incidence increases with ST-elevation MI STEMI and decreases with non-STEMI (NSTEMI). Of all patients who have an acute MI, about 90% develop some form of cardiac arrhythmias. In 25% of patients, such rhythm abnormalities occur within the first 24 hours. The risk of serious arrhythmias, such as ventricular fibrillation (VF), is greatest in the first hour and then declines thereafter. 

Most peri-infarction arrhythmias are benign and self-limited. However, aggressively monitor and treat arrhythmias that result in hypotension, increase myocardial oxygen requirements, and/or predispose the patient to malignant ventricular arrhythmias.

Mechanical complications

The three major mechanical complications of MI, each of which can cause cardiogenic shock, are as follows:

  • Ventricular free wall rupture

  • Ventricular septal defect

  • Papillary muscle rupture with severe mitral regurgitation

Left ventricular aneurysm formation

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 aneurysm formation after acute MI is approximately 3-15%. Risk factors for these aneurysms after acute MI include the following:

  • Female sex

  • Total occlusion of the left anterior descending (LAD) coronary artery

  • Single-vessel coronary artery disease (CAD)

  • Absence of previous angina pectoris

Clinically, ventricular aneurysms may be recognized late, with symptoms and signs of heart failure, recurrent ventricular arrhythmias, or recurrent embolization.

Ventricular septal defect

Ventricular septal rupture (acute ventricular septal defect) is a rare but critical complication of MI. It 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.

Ventricular rupture is more common in patients with anterior MI, individuals with hypertension, and those receiving nonsteroidal anti-inflammatory drugs (NSAIDs) or steroids.

To avoid the high morbidity and mortality associated with ventricular septal rupture, patients should undergo emergent surgery.[121, 122]

Concomitant coronary artery bypass grafting (CABG) may be required. Developments in myocardial protection and improved prosthetic materials have contributed greatly to successful management of ventricular septal rupture.[123] 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 a greater than 90% mortality. Prompt recognition, stabilization, and surgical repair are crucial for patient survival. 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 MI develop right ventricular infarction, which presents a special challenge because the adjunctive therapy, other than reperfusion, is somewhat different.

A right-sided electrocardiogram (ECG) with a more than 1-mm ST elevation in lead V3 R or V4 R describes a right ventricular infarction. An echocardiogram may be helpful in confirming the diagnosis.

On physical examination, signs of right-sided heart failure may be present, such as elevated jugular venous pulsation, right-sided S3, Kussmaul sign, or hypotension, but the patient may have clear lung fields.

The patient becomes volume dependent to maintain adequate left and right ventricular filling. Occasionally, dobutamine may be needed, or even an intraaortic 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.

Ventricular pseudoaneurysm

Complications of MI, such as ventricular pseudoaneurysms, are confirmed by means of echocardiography,magnetic resonance imaging (MRI), or contrast-enhanced computed tomography (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 angiography by the presence of mural vessels.

Miscellaneous complications

Left ventricular mural thrombus 

Left ventricular mural thrombus Is a well-known complication of acute anterior MI and frequently develops after left anterior wall infarction. The incidence of left ventricular mural thrombus as a complication of acute MI ranges from 20% to 40% but may reach 60% in patients with large, anterior-wall acute MIs who are not treated with anticoagulant therapy.

Left ventricular mural thrombus is associated with high risk of systemic embolization. Anticoagulant therapy may substantially decrease the rate of embolic events by 33% compared with no anticoagulation.

Pericarditis

The incidence of early pericarditis after MI is approximately 10%, and this complication usually develops within 24-96 hours after MI. Pericarditis is caused by inflammation of pericardial tissue overlying the 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-MI pericarditis (Dressler syndrome) ranged from 1% to 5% after acute MI, but this rate has dramatically declined with the advent of thrombolysis and percutaneous coronary intervention (PCI).

Future and Emerging Therapies

Local injection of progenitor cells, growth factors, or stem cells may stimulate vascular development. Stem cell therapies for acute myocardial infarction (MI) remain a major target of research, with some data showing modest results.[124] Investigators in the Reinfusion of Enriched Progenitor Cells And Infarct Remodeling in Acute Myocardial Infarction (REPAIR-AMI) study examined 204 patients with acute ST-elevation MI (STEMI) and reported greater improvement in left ventricular ejection fraction (LVEF) among patients who received intracoronary progenitor cell infusion than among those given placebo.[125]

Several smaller clinical trials have suggested that intracoronary delivery of autologous bone marrow mononuclear cells (BMCs) have improved left ventricular function when administered within the first week following MI. However, results from the LateTIME Randomized Trial that evaluated whether intracoronary delivery of autologous BMCs delivered 2-3 weeks following first MI improved global and regional left ventricular function when compared with placebo suggested little improvement with this strategy in patients with MI and left ventricular dysfunction following reperfusion with percutaenous coronary intervention (PCI).[126]

 

Guidelines

Guidelines Summary

The American College of Cardiology Foundation and the American Heart Association (ACCF/AHA) as well as the European Society of Cardiology (ESC) have developed guidelines for management of patients with ST-segment elevation myocardial infarction (STEMI).[2, 4, 70]  

Prehospital and emergency care

The 2013 ACCF/AHA and the 2012 and 2017 ESC guidelines stress the importance of obtaining a 12-lead electrocardiogram (ECG) in a timely fashion (≤10 mins of presentation) in their recommendations (class I, level of evidence: B, for all three guidelines).[2, 4, 70]  The 2017 ESC guidelines also recommend ECG monitoring with defibrillator capacity as soon as possible in all patients with suspected STEMI (class I, level of evidence: B) but do not recommend prehospital cooling with a rapid infusion of large volumes of cold intravenous fluid immediately after return of spontaneous circulation (class IIa, level of evidence: C).[70]

Other ACCF/AHA recommendations for patients with STEMI include those summarized below.[2]

Class I

Level of evidence: A

Reperfusion therapy should be administered to all eligible STEMI patients with symptomatic onset within the previous 12 hours. The recommended reperfusion method is primary PCI when it can be performed expediently by experienced clinicians.

Level of evidence: B

Direct emergency medical services (EMS) transport of STEMI patients to a PCI-capable hospital for primary PCI is recommended, with an ideal first medical contact (FMC)-to-device time system goal of 90 minutes or shorter.

For patients who initially arrive at a non–PCI-capable hospital, immediate transfer to a PCI-capable hospital is recommended, with an FMC-to-device time system goal of 120 minutes or shorter.

In the absence of contraindications and when the anticipated FMC-to-device time exceeds 120 minutes because of unavoidable delays, fibrinolytic therapy should be administered to STEMI patients at non–PCI-capable hospitals. When fibrinolytic therapy is indicated or chosen as the primary reperfusion strategy, it should be administered within 30 minutes of hospital arrival.

Initiate therapeutic hypothermia as soon as possible in comatose STEMI patients with out-of-hospital cardiac arrest caused by ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT), including patients who undergo primary PCI.

For resuscitated out-of-hospital cardiac arrest patients whose initial ECG shows STEMI, immediate angiography and PCI should be performed when indicated.

Class IIa

Primary PCI is the preferred reperfusion strategy for patients with STEMI and symptom onset within the prior 12 to 24 hours in the presence of clinical and/or ECG evidence of ongoing ischemia. (Level of evidence: B)

 

The 2012 and 2017 ESC guidelines concur with the ACCF/AHA recommendations and additionally recommend routine blood sampling for serum markers in the acute phase.[4, 70]  However, do not delay initiation of reperfusion therapy for the results. (Class I, level of evidence: C) The 2017 ESC guidelines also indicate the following should be considered for the initial diagnosis (class IIa, level of evidence B for both)[70] :

  • The use of additional posterior chest wall leads (V 7-V 9) when a posterior MI (circumflex occlusion) is highly suspected
  • The use of additional right precordial leads (V 3R and V 4R) in the presence of an inferior MI to identify concomitant right ventricular infarction

Percutaneous Coronary Intervention

Recommendations for percutaneous coronary intervention (PCI) from the 2013 update of the American College of Cardiology/American Heart Association (ACC/AHA) guidelines for management of ST-elevation myocardial infarction (STEMI),[2]  the 2014 European Society of Cardiology/European Association for Cardio-Thoracic Surgery (ESC/EACTS),[127] and 2017 ESC guidelines for myocardial revascularization,[70]  include the following:

  • Primary PCI is indicated in patients with ischemic symptoms shorter than 12 hours and contraindications to thrombolytic therapy (irrespective of the time delay from FMC); and in patients with cardiogenic shock or acute severe heart failure, irrespective of the time delay from MI onset (Class I, level of evidence: A)
  • Primary PCI is reasonable in patients with ongoing ischemia 12-24 hours after symptom onset (Class IIb)

2015 ACC/AHA/SCAI guidelines

In 2015 the ACC/AHA and Society for Cardiovascular Angiography and Interventions (ACC/AHA/SCAI) issued revised recommendations for PCI in STEMI patients, as indicated below.[128]

Class IIb

PCI of a noninfarct artery may be considered in selected hemodynamically stable STEMI patients with multivessel disease, either at the time of primary PCI or as a planned staged procedure. (Level of evidence: B-R)

The efficacy of selective and bailout aspiration thrombectomy in patients undergoing primary PCI remains to be established. (Level of evidence: C-LD)

Class III

PCI should not be performed in a noninfarct artery at the time of primary PCI in hemodynamically stable STEMI patients. (Level of evidence: B)

Routine aspiration thrombectomy before primary PCI is not useful. (Level of evidence: A)

 

The 2017 ESC guidelines recommend primary PCI of the infarct-related artery (class I, level of evidence: A), as well as new coronary angiography with PCI in patients with symptoms/signs or recurrent or remaining ischemia following primary PCI (class I, level of evidence: C).[70]  Note that in patients with coronary artery occlusion/global ischemia in the absence of characteristic ST elevation (eg, bundle branch block, ventricular pacing, hyperacute T-waves, isolated ST-depression in the anterior leads, and/or universal ST depression with ST-elevation in lead aVR) who have a clinical presentation compatible with ongoing myocardial ischemia, a primary PCI strategy (ie, urgent angiography and PCI, if indicated) is recommended.[70]

The 2017 ESC guidelines also indicate that the following should be considered for noninfarct arteries (all class IIa)[70] :

  • Routine revascularization of noninfarct arteries in those with STEMI and multivessel disease before hospital discharge (Level of evidence: A)
  • PCI of the noninfarct artery during the index procedure in those with cardiogenic shock (Level of evidence: C)
  • CABG in patients with ongoing ischemia and large areas of at-risk myocardium if the infarct artery is not amenable to PCI (Level of evidence: C)

2011 ACCF/AHA/SCAI guidelines 

The 2011 ACCF/AHA/SCAI guidelines for PCI provides the following guidance with regard to the selection of bare-metal stents (BMS) or drug-eluting stents (DES)[129] :

  • Before DES implantation, the need for, and duration of, dual antiplatelet therapy (DAPT) and the ability of the patient to comply with and tolerate DAPT should be discussed with the patient. (Class I, level of evidence: C)
  • DES are useful alternatives to bare-metal stents (BMS) to reduce the risk of restenosis in cases in which there is an elevated risk of restenosis and the patient is likely to be able to tolerate and comply with prolonged DAPT. (Class I, level of evidence: A)
  • BMS should be used in patients with high bleeding risk, an inability to comply with 1 year of DAPT, or anticipated invasive or surgical procedures in the next 1 year. (Class I, level of evidence: B)
  • DES implantation should not be performed in patients who are probably unable to tolerate or comply with a prolonged course of DAPT. (Class III, level of evidence: B)

2014 ESC/EACTS and 2017 ESC recommendations

In its 2014 update, the ESC/EACTS significantly diverged from its previous recommendations and those of ACC/AHA above. It recommends unrestricted use of new-generation DES, finding that previous concerns regarding the duration of DAPT, and the risks associated with DAPT cessation were unsubstantiated.[127]  Based on evidence of increased efficacy and safety, ESC/EACTS considers new-generation DES the default in all clinical conditions and lesion subsets where PCI is indicated.[127]

In the 2017 ESC guidelines, the recommendations for primary PCI reiterate that stenting is preferred over balloon angioplasty and that new-generation DES are preferred over baremetal stents (both class I, level of evidence: A).[70] In addition, if performed by an experienced radial operator, radial access is preferred over femoral access (class I, level of evidence: A).

2013 ACC/AHA guidelines

In the 2013 ACC/AHA guidelines for management of STEMI, recommendations for antithrombotic therapy in patients undergoing primary PCI include those below[2] :

Class I

  • For supportive anticoagulant therapy: Unfractionated heparin (UFH), with additional boluses as needed to maintain therapeutic activated clotting time levels, accounting for whether a GP IIb/IIIa receptor antagonist has been administered (level of evidence: C); or bivalirudin with/without UFH prior therapy. (Level of evidence: B)

Class IIa

  • For STEMI patients at high risk of bleeding, bivalirudin monotherapy may be preferred over the combination of UFH and a GP IIb/IIIa receptor antagonist. (Level of evidence: B)

Class III

  • PCI should not be performed with fondaparinux as the sole antithrombin agent. (Level of evidence: B)

 

The 2014 ESC/EACTS and the 2017 ESC guidelines vary from ACC/AHA in that use of both bivalirudin and enoxaparin (with/without GP IIb/IIIa receptor antagonist) are given a class IIa recommendation.[127, 70]

 

For patients undergoing PCI after receiving fibrinolytic therapy, ACC/AHA recommends the following[2] :

Class I

  • For STEMI patients treated with IV UFH: Additional boluses of UFH as needed during PCI, taking into account whether a GP IIb/IIIa receptor antagonist has been administered
  • For STEMI patients treated with enoxaparin: If the last subcutaneous dose was administered within the previous 8 hours, no additional enoxaparin should be given; if the last subcutaneous dose was received 8-12 hours prior to the procedure, an additional dose of enoxaparin 0.3 mg/kg IV  should be administered at the time of PCI.

Class III

  • PCI should not be performed with fondaparinux as the sole antithrombin agent. An additional anticoagulant with anti-IIa activity should be administered because of the risk of catheter thrombosis.

For patients undergoing PCI after receiving fibrinolytic therapy, ACC/AHA recommends the following[2] :

Class I

  • Aspirin should be continued indefinitely. (Level of evidence: A)
  • Clopidogrel 300 mg loading dose should be given before or at the time of PCI to patients who did not receive a previous loading dose and who are undergoing PCI within 24 hours of receiving fibrinolytic therapy. (Level of evidence: C)
  • Clopidogrel 600 mg loading dose should be given before or at the time of PCI to patients who did not receive a previous loading dose and who are undergoing PCI more than 24 hours after receiving fibrinolytic therapy (Level of evidence: C)
  • Administer a 75-mg dose of clopidogrel after PCI (Level of evidence: C)

Class IIa

  • After PCI, aspirin 81 mg per day is preferable to higher maintenance doses. (Level of evidence: B)
  • Prasugrel 60 mg loading dose is reasonable in patients who did not receive a previous loading dose of clopidogrel at the time of administration of a fibrinolytic agent, but it should not be given sooner than 24 hours after administration of a fibrin-specific agent or 48 hours after administration of a non–fibrin-specific agent. (Level of evidence: B)
  • A 10-mg daily maintenance dose of prasugrel is reasonable after PCI. (Level of evidence: B)

Class III

  • Prasugrel is contraindicated in patients with a previous history of stroke or transient ischemic attack. (Level of evidence: B)

Coronary Artery Bypass Grafting

2014 ACC/AHA guidelines

The 2014 American College of Cardiology/American Heart Association (ACC/AHA) guidelines view coronary artery bypass grafting (CABG) as having a limited role in the acute phase of ST-elevation myocardial infarction (STEMI), but they provide a class I recommendation for CABG in patients whose coronary anatomy is not amenable to percutaneous coronary intervention (PCI) and who have ongoing or recurrent ischemia or cardiogenic shock.[2]

CABG is also recommended (class I) in patients with STEMI at time of operative repair of mechanical defects such as[2] :

  • Ventricular septal defect related to myocardial infarction (MI)
  • Papillary muscle rupture
  • Free wall rupture

Emergency CABG is not recommended in patients with the following conditions[130] :

  • Persistent angina, a small area of viable myocardium, and hemodynamically stable
  • No-reflow state (successful epicardial reperfusion with unsuccessful microvascular reperfusion)

In addition, CABG is not advised for patients with ventricular tachycardia with scar and no evidence of ischemia.[130]

The 2017 European Society of Cardiology guidelines indicate emergent CABG should be considered in patients with a patent infarct-related artery whose anatomy is unsuitable for PCI, and either a large at-risk myocardial area or with cardiogenic shock.[70] The benefits of surgical revascularization are unclear in the setting of emergent CABG in patients who have experienced a failed PCI or have a coronary occlusion not amenable to PCI. CABG is recommended at the time of repair for those with mechanical complications associated with MI who require coronary revascularization.[70]

ACC/AHA recommendations for emergency CABG after failed PCI include the following[130] :

  • Ongoing ischemia or threatened occlusion with substantial myocardium at risk (Class I)
  • Hemodynamic compromise without impairment of coagulation and without a previous sternotomy (Class I)
  • Hemodynamic compromise with impairment of coagulation and without a previous sternotomy (Class IIa)
  • Hemodynamic compromise and previous sternotomy (Class IIb)
  • Retrieval of a foreign body (eg, fractured guidewire or stent) in a crucial location (Class IIa)

2015 AHA scientific statement

In 2015, the AHA published a scientific statement on secondary prevention after CABG with the following recommendations[131] :

  • Administer aspirin within 6 hours after CABG in doses of 81 to 325 mg daily. Continue aspirin indefinitely to reduce graft occlusion and adverse cardiac events. (Class I, level of evidence: A)

  • After off-pump CABG, administer dual antiplatelet therapy (DAPT)  for 1 year with combined aspirin (81-162 mg daily) and clopidogrel (75 mg daily) to reduce graft occlusion. (Class I, level of evidence: A)

  • After CABG, clopidogrel 75 mg daily is a reasonable alternative for patients who cannot take aspirin. (Class IIa, level of evidence: C)

  • In patients who present with acute coronary syndrome (ACS), it is reasonable to administer combination antiplatelet therapy with aspirin and either prasugrel or ticagrelor (preferred over clopidogrel) (Class IIa, level of evidence: B)

  • After on-pump CABG, combination therapy with aspirin and clopidogrel for 1 year may be considered in patients without recent ACS, but the benefits are not well established. (Class IIb, level of evidence: A)

  • Warfarin should not be routinely prescribed after CABG for graft patency unless patients have other indications for long-term antithrombotic therapy (such as atrial fibrillation [AF], venous thromboembolism, or a mechanical prosthetic valve). (Class III, level of evidence: A)

  • Antithrombotic alternatives to warfarin (dabigatran, apixaban, rivaroxaban) should not be routinely administered after CABG. (Class III, level of evidence: C)

  • CABG patients should receive statin therapy, starting in the preoperative period and restarting early after surgery. (Class I, level of evidence: A)

  • Administer postoperative high-intensity statin therapy (atorvastatin 40-80 mg, rosuvastatin 20-40 mg) to all CABG patients younger than 75 years. (Class I, level of evidence: A)

  • Administer moderate-intensity statin therapy for those patients who are intolerant of high-intensity statin therapy and for those at greater risk for drug-drug interactions (ie, patients aged >75 years). (Class I, level of evidence: A)

  • Pre- or post-CABG discontinuation of statin therapy is not recommended unless patients have adverse reactions to therapy. (Class III, level of evidence: B)

  • Administer beta-blockers as soon as possible around the time of CABG, in the absence of contraindications, to reduce the risk of postoperative AF and to facilitate blood pressure (BP) control early after surgery. (Class I, level of evidence: A)

  • Administer angiotensin-converting enzyme (ACE) inhibitor therapy after CABG for patients with recent MI, left ventricular (LV) dysfunction, diabetes mellitus, and chronic kidney disease. Carefully consider the patient's renal function in determining the timing of postoperative ACE inhibitor initiation and dose selection. (Class I, level of evidence: B)

  • Routine ACE inhibitor therapy is not recommended early after CABG among patients without a history of recent MI, LV dysfunction, diabetes mellitus, or chronic kidney disease, because it may lead to more harm than benefit and an unpredictable BP response. (Class III, level of evidence: B)

  • Cardiac rehabilitation is recommended for all patients after CABG, with the referral ideally performed early during the surgical hospital stay. (Class I, level of evidence: A)

Mechanical Circulatory Support

The following organizations released guidelines for the utilization of mechanical circulatory support (MCS):

  • Society for Cardiovascular Angiography and Interventions, American College of Cardiology, Heart Failure Society of America, and Society for Thoracic Surgeons (SCAI/ACC/HFSA/STS)
  • International Society of Heart and Lung Transplantation (ISHLT)
  • American Heart Association (AHA)

2015 SCAI/ACC/HFSA/STS consensus statement

In a 2015 clinical expert consensus statement by the SCAI/ACC/HFSA/STS noted that historically the intraaortic balloon pump (IABP) and extracorporeal membrane oxygenation (ECMO) devices had been the only MCS devices available to clinicians, but axial flow pumps, such as Impella and left atrial to femoral artery bypass pumps, such the TandemHeart have more recently entered clinical practice. The consensus-based recommendations included the following[132] :

  • Percutaneous circulatory assist devices provide superior hemodynamic support compared with pharmacologic therapy, which is particularly apparent for the Impella and Tandem-Heart devices.
  • In those with cardiogenic shock who fail to stabilize or show signs of improvement after initial interventions, consider early placement of an appropriate MCS.
  • In patients with cardiogenic shock, continuous flow pumps (eg, Impella CP, TandemHeart) are more likely to provide clinical benefit than IABP. ECMO may provide particular benefit for patients with impaired respiratory gas exchange.
  • Consider MCS for isolated acute right ventricular failure that is complicated by cardiogenic shock.
  • Consider MCS in the setting of high-risk percutaneous coronary intervention (PCI) (eg, multivessel, left main, or last patent conduit interventions), particularly if the patient is inoperable or has severely decreased ejection fraction or elevated cardiac filling pressures.
  • Consider MCS in patients who fail to wean off of cardiopulmonary bypass.
  • Consider early MCS in patients with acute decompensated heart failure who continue to deteriorate despite initial interventions.
  • MCS may be necessary in the setting of severe biventricular failure via both right- and left-sided percutaneous devices or venoarterial ECMO.

However, there was insufficient evidence regarding the routine use of MCS as an adjunct to primary revascularization to reduce reperfusion injury or infarct size in patients with large acute MI.[132]

2013 ISHLT guidelines

In its 2013 guidelines for mechanical circulatory support, the ISHLT recommended long-term MCS for acute cardiogenic shock in the following patient settings (Class IIa, level of evidence: C)[133] :

  • When ventricular function is deemed unrecoverable or unlikely to recover without long-term device support
  • Severely ill and unable to maintain normal hemodynamics and vital organ function with temporary MCS, or cannot be weaned from temporary MCS or inotropic support
  • Has the capacity for meaningful recovery of end-organ function and quality of life
  • Absence of irreversible end-organ damage

Additional recommendations include[133] :

  • If possible, delay permanent MCS in the setting of an acute infarct involving the left ventricular (LV) apex. (Class IIb, level of evidence: C)
  • Perform echocardiography as part of the preoperative assessment and routinely at regular postoperative intervals to evaluate for signs of myocardial recovery and optimal MCS device function. This imaging modality may be used to set optimal pump parameters. (Class I, level of evidence: B)
  • In addition, perform echocardiography to evaluate suboptimal MCS device function or in the presence of clinical signs of circulatory dysfunction, including congestive or low output symptoms. (Class I, level of evidence: B)

Dual Antiplatelet Therapy

In 2016, the American College of Cardiology and American Heart Association (ACC/AHA) released updated guidelines on duration of dual antiplatelet therapy (DAPT) in patients with coronary artery disease.[134] In this focused update, the term and acronym DAPT is used to specifically to refer to combination antiplatelet therapy with aspirin and a P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor).

2016 ACC/AHA guidelines

Key recommendations for patients with non–ST elevation acute coronary syndrome (NSTE-ACS) or ST-elevation myocardial infarction(STEMI) treated with DAPT are summarized below.[134]

Class I

For all patients treated with DAPT, administer a daily aspirin dose of 81 mg (range, 75-100 mg). (Level of evidence: B-NR)

After bare-metal stent (BMS) or drug-eluting stent (DES) implantation in patients with ACS, P2Y12 inhibitor therapy (clopidogrel, prasugrel, or ticagrelor) should be given for at least 1 year. (Level of evidence: B-R)

For patients who subsequently undergo coronary artery bypass grafting (CABG) after coronary stent implantation, resume P2Y12 inhibitor therapy postoperatively to maintain DAPT until the recommended duration of therapy is completed. (Level of evidence: C-EO)

In ACS patients who undergo CABG, resume P2Y12 inhibitor therapy after CABG to complete 1 year of DAPT therapy. (Level of evidence: C-LD) 

Patients with STEMI treated with DAPT and fibrinolytic therapy should continue P2Y12 inhibitor therapy (clopidogrel) for at least 14 days (level of evidence: A) and, ideally, at least 1 year (level of evidence: C-EO).

Class IIa

After coronary stent implantation in the setting of ACS, ticagrelor is preferred over clopidogrel for maintenance P2Y12 inhibitor therapy. (Level of evidence: B-R)

After coronary stent implantation in ACS patients treated with DAPT who are not at high risk for bleeding complications and who do not have a history of stroke or transient ischemic attack (TIA), it is reasonable to choose prasugrel over clopidogrel for maintenance P2Y12 inhibitor therapy. (Level of evidence: B-R)

Class IIb

In patients treated with coronary stent implantation or fibrinolytic therapy who have tolerated DAPT without a bleeding complication and who are not at high bleeding risk, continuation of DAPT (clopidogrel, prasugrel, or ticagrelor) for longer than 1 year may be reasonable. (Level of evidence: A)

After DES implantation, patients who develop a high risk of bleeding or are at high risk of severe bleeding complication, or who develop significant overt bleeding, discontinuation of P2Y12 inhibitor therapy after 6 months may be reasonable. (Level of evidence: C-LD)

Class III

Prasugrel should not be administered to patients with a previous history of stroke or TIA. (Level of evidence: B-R)

 

Medication

Medication Summary

The goals of pharmacotherapy for myocardial infarction are to reduce morbidity and to prevent complications. The main goals of emergency department medical therapy are rapid intravenous thrombolysis and/or rapid referral for percutaneous coronary intervention (PCI), optimization of oxygenation, reduction of cardiac workload, and pain control.[70]

Antiplatelet Agents

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.

Antithrombotic Agents

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.

Glycoprotein IIb/IIIa Inhibitors

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.

Vasodilators

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.

Beta-adrenergic blockers

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.

Angiotensin-Converting Enzyme Inhibitors

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.

Angiotensin-Receptor Blockers

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.

Thrombolytics

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.

Analgesics

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.

PCSK9 Inhibitors

Class Summary

Over the last decade, inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising target to reduce residual cardiovascular disease risk. PCSK9 is a protein that binds to low-density lipoprotein (LDL) receptors (LDLR) to promote their degradation. Monoclonal antibodies inhibit PCSK9 and thus prevent LDLR degradation. This action will increase the number of LDLRs and subsequently increase the clearance of LDL, ultimately lowering LDL-C levels. 

In December 2017, the FDA approved the first PCSK9 inhibitor, evolocumab (Repatha), for the prevention of strokes, heart attacks, and coronary revascularizations.[64] The approval was based on data from the evolocumab cardiovascular outcomes study (FOURIER). In the FOURIER clinical trial, evolocumab demonstrated significant benefits for 27,564 patients with established cardiovascular disease. The study revealed that when used in addition to optimized statin therapy, evolocumab reduced the risk of heart attack by 27%, the risk of stroke by 21%, and the risk of coronary revascularization by 22%. In addition, evolocumab showed a statistically significant 15% reduction in the risk of the primary composite endpoint, which included hospitalization for unstable angina, coronary revascularization, heart attack, stroke, or cardiovascular death.[65]

In April 2019, the FDA expanded the indication for alirocumab (Praluent) to include risk reduction of MI, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease.[135] Approval was based on the ODYSSEY OUTCOMES trial (N=18,924) in patients with elevated LDL-C despite treatment with maximally tolerated statins. Patients who received injections of alirocumab 75 mg or 150 mg every other week achieved reduction in the risk for major cardiovascular events by 15% and all-cause death by 15% at a median follow-up of 2.8 years compared with those who received placebo.[136]

Evolocumab (Repatha)

Human monoclonal IgG2 directed against PCSK9. Evolocumab binds to PCSK9 and inhibits circulating PCSK9 from binding to the LDLR, preventing PCSK9-mediated LDLR degradation and permitting LDLR to recycle back to the liver cell surface. By inhibiting the binding of PCSK9 to LDLR, evolocumab increases the number of LDLRs available to clear LDL from the blood, thereby lowering LDL-C levels. 

Alirocumab (Praluent)

Monoclonal antibody that binds to PCSK9. LDL-C is cleared from the circulation preferentially through the LDL receptor (LDLR) pathway. PCSK9 is a serine protease that destroys LDLR in the liver, resulting in decreased LDL-C clearance and increased plasma LDL-C.

 

Questions & Answers

Overview

What are the irregular vital signs that may be observed in myocardial infarction (MI, heart attack)?

What is myocardial infarction (MI, heart attack), and what is the annual incidence in the US?

Which symptoms are recognized as common warning signs preceding a myocardial infarction (MI, heart attack)?

What are the characteristics of typical chest pain in acute myocardial infarction (MI, heart attack)?

Which lab tests are useful in the diagnosis of myocardial infarction (MI, heart attack)?

What is the most important diagnostic tool in the initial evaluation of suspected myocardial infarction (MI, heart attack)?

What is the role of coronary angiography in suspected myocardial infarction (MI, heart attack)?

What prehospital care is indicated in chest pain and suspected myocardial infarction (MI, heart attack)?

Which medications should be used to stabilize patients with ongoing acute chest pain and suspected myocardial infarction (MI, heart attack)?

When is emergent coronary angiography and primary PCI indicated in STEMI (heart attack), and which treatment should be considered if PCI is not available?

What is the initial treatment approach in non-ST-segment elevation acute coronary syndrome (non-STE-ACS, NSTEMI, MI, heart attack)?

What is the role of coronary care units, and how beneficial are they in the treatment of myocardial infarction (MI, heart attack)?

What is the etiology of myocardial infarction (MI, heart attack)?

What is the role of cardiac biomarkers in the evaluation of myocardial infarction (MI, heart attack)?

How is myocardial infarction (MI, heart attack) associated with acute coronary syndrome (ACS)?

What are the potential long-term complications of myocardial infarction (MI, heart attack)?

What is the role of coronary thrombolysis and mechanical revascularization in acute myocardial infarction (MI, heart attack)?

What are the benefits of late recanalization of an infarct-related artery in acute myocardial infarction (MI, heart attack)?

What are the treatment options that can be used to supplement coronary thrombolysis and mechanical revascularization in the treatment of myocardial infarction (MI, heart attack)?

What is a myocardial infarction (MI, heart attack), and what is the most common symptom?

What are the criteria used to diagnose myocardial infarction (MI, heart attack)?

What are the types of myocardial infarction (MI, heart attack), and how is each defined?

What is acute coronary syndrome (ACS), and what are the two main categories of ACS?

What is myocardial ischemia, and how does it ultimately lead to myocardial infarction (MI, heart attack)?

What are the factors that contribute to myocardial injury, and what is the result of persistent oxygen deprivation to the myocardium?

What is the role of coagulation necrosis in myocardial infarction (MI, heart attack), and how does myocardial fibrosis contribute to ventricular remodeling?

What is reperfusion injury, and how might it be prevented?

What are stunned myocardium and myocardial hibernation, and how do they occur?

How does the atheromatous plaque responsible for acute myocardial infarction (MI, heart attack) develop, and what is its role in acute coronary syndrome (ACS)?

What is the etiology of acute coronary syndrome (ACS)?

What are the nonmodifiable risk factors and the modifiable risk factors for atherosclerosis?

What are the causes of myocardial infarction (MI, heart attack) other than atherosclerosis?

What conditions are associated with pediatric coronary artery disease, and what are the factors that contribute to acute myocardial infarction (MI, heart attack) in childhood and adolescence?

What is the mortality rate associated with coronary artery disease (CAD) in the US?

Which risk factors for coronary artery disease (CAD) were identified in the INTERHEART study?

What is the incidence of myocardial infarction (MI, heart attack) in the US?

Which groups are at highest risk of mortality due to acute myocardial infarction (MI, heart attack)?

How have the mortality rates of coronary artery disease (CAD) and myocardial infarction (MI, heart attack) changed outside the US?

What is the prognosis of acute myocardial infarction (MI, heart attack)?

Which factors are associated with a better prognosis of myocardial infarction (MI, heart attack)?

Which factors are associated with a worse prognosis of myocardial infarction (MI, heart attack)?

Which baseline parameters are prognostic predictors of 30-day mortality due to acute myocardial infarction (MI, heart attack)?

What is the Killip classification system and how is it used in acute myocardial infarction (MI, heart attack)?

What should patients do when they experience active symptoms of acute coronary syndrome (ACS) (MI, heart attack)?

How is nitroglycerin used in patients at risk for acute coronary syndrome (ACS) when they experience symptoms?

What is the role of diet and exercise in the treatment of a cardiovascular event (MI, heart attack)?

What educational resources are available for patients with coronary artery disease (CAD) or myocardial infarction (MI, heart attack)?

Presentation

What is the role of patient history in diagnosing myocardial infarction (MI, heart attack), and what are the typical presenting symptoms?

When time of day does myocardial infarction (MI, heart attack) most often occur, and what mechanisms are involved?

What should initial rapid evaluation for myocardial infarction (MI, heart attack) include?

What is the role of risk assessments in the evaluation of acute coronary syndrome (ACS) symptoms?

Which patients require a high index of suspicion of myocardial infarction (MI, heart attack)?

In addition to chest pain, what other symptoms of myocardial infarction (MI, heart attack) should be considered when evaluating a patient for MI?

What is the role of heart rate in the evaluation of symptoms of myocardial infarction (MI, heart attack)?

How can physical exam findings vary in myocardial infarction (MI, heart attack)?

What is the role of blood pressure in the evaluation of symptoms of myocardial infarction (MI, heart attack)?

Why might respiratory rate be elevated in myocardial infarction (MI, heart attack)?

How is body temperature associated with myocardial infarction (MI, heart attack)?

What do distended neck veins indicate in the setting of myocardial infarction (MI, heart attack)?

Which heart exam findings are associated with heart damage in the setting of myocardial infarction (MI, heart attack)?

Which chest exam findings are associated with myocardial infarction (MI, heart attack)?

Which abdominal exam findings are associated with myocardial infarction (MI, heart attack)?

Which findings on physical exam of the extremities are associated with myocardial infarction (MI, heart attack)?

DDX

Which GI symptoms are associated with myocardial ischemia and myocardial infarction (MI, heart attack)?

Which musculoskeletal symptoms are associated with myocardial ischemia and myocardial infarction (MI, heart attack)?

Why is myocardial infarction misdiagnosed more often in younger patients?

How can ischemic changes be more readily recognized in myocardial infarction (MI, heart attack), and what are common nonischemic causes of ST-segment elevation?

What are the differential diagnoses for Myocardial Infarction?

Workup

What are the objectives of lab testing and imaging studies in myocardial infarction (MI, heart attack)?

What is the most important tool in the initial evaluation of suspected acute coronary syndrome (ACS) or myocardial infarction (MI, heart attack)?

Which lab tests do guidelines recommend in the workup of myocardial infarction (MI, heart attack)?

What is the role of ECG in the initial evaluation of patients with suspected acute coronary syndrome (ACS) or myocardial infarction (MI, heart attack)?

What are the criteria for using ECG in the workup of suspected myocardial infarction (MI, heart attack), and how often should it be performed?

Why is ECG an effective tool in detecting myocardial ischemia and acute myocardial infarction (MI, heart attack)?

What are the ECG features in ST-elevation myocardial infarction (STEMI) (MI, heart attack)?

What are the high-, intermediate-, and low-probability ECG features of myocardial infarction (MI, heart attack)?

How is the distribution of ECG abnormalities associated with the involved myocardium in myocardial infarction (MI, heart attack)?

How is posterior-wall myocardial infarction (MI, heart attack) identified on ECG?

What can abnormalities in a large number of ECG leads indicate in myocardial infarction (MI, heart attack)?

What ECG findings characteristic of myocardial infarction (MI, heart attack) may be seen in other conditions?

What does convex ST-segment elevation with upright or inverted T waves on ECG generally indicate in myocardial infarction (MI, heart attack)?

How can a permanent pacemaker affect the recognition of STEMI on ECG?

What are the non-ischemic causes of ST-segment elevation?

Which cardiac biomarkers have been used to evaluate suspected acute myocardial infarction (MI, heart attack)?

How has cardiac troponin detection and quantification changed over the years, and when should serial measurements of cardiac troponins be obtained?

How often should cardiac troponins be measured after the initial level is obtained at presentation?

What is troponin and when is it found in serum?

According to guidelines, what is the role of cardiac troponin testing in the diagnosis and prognosis of acute myocardial infarction (MI, heart attack)?

How long are troponin serum levels elevated in myocardial infarction (MI, heart attack), and what is the role of troponin testing in chest pain?

What is B-type natriuretic peptide (BNP), and what is its role in the workup of myocardial infarction (MI, heart attack)?

When should a CBC count be obtained in suspected myocardial infarction (MI, heart attack), and which conditions should be excluded prior to thrombolytic therapy?

When is a platelet count necessary in the workup of suspected myocardial infarction (MI, heart attack), and what may abnormal results indicate?

Which lab values should be closely monitored in patients with myocardial infarction (MI, heart attack)?

What are the causes of hypoxemia in patients with myocardial infarction (MI, heart attack), and how are oxygen levels monitored?

What is the role of a lipid profile in the workup of myocardial infarction (MI, heart attack)?

What is the role of imaging in the work-up of acute myocardial infarction (MI, heart attack)?

What is the role of coronary angiography in the workup of acute coronary syndrome (ACS), and which treatment options may be indicated by the results?

Which imaging study is an alternative to invasive angiography to exclude acute coronary syndrome (ACS) when there is a low to intermediate likelihood of coronary artery disease (CAD)?

What is the efficacy of myocardial perfusion imaging (MPI) with SPECT or PET scanning in myocardial infarction (MI, heart attack)?

What is the role of ECG in the workup of acute myocardial infarction (MI, heart attack)?

Treatment

What is the first goal in the management of acute myocardial infarction (MI, heart attack), and what is the objective of the initial therapy?

Why is it important to distinguish STEMI from non-STEMI in the initial evaluation of acute coronary syndrome (ACS)?

What is the role of evolocumab (Repatha) in the prevention of prevention of strokes, myocardial infarction (MI), and coronary revascularization?

How can morbidity and mortality from myocardial infarction (MI, heart attack) be significantly reduced, and what is the key to improved survival?

Why is effective communication between EMS personnel and emergency department staff important?

What prehospital care can be provided by EMS personnel in patients with myocardial infarction (MI, heart attack)?

What causes most myocardial infarction-related deaths, and what can prehospital care providers do to improve outcomes?

What are the secondary objectives of prehospital care by paramedical and emergency personnel in myocardial infarction (MI, heart attack)?

When is prehospital fibrinolytic therapy indicated for myocardial infarction (MI, heart attack), and what is its availability?

How is an initial evaluation of acute myocardial infarction (MI, heart attack) performed in the emergency department?

What are the goals of the overall management plan for acute myocardial infarction (MI, heart attack)?

When are oxygen saturation monitoring via pulse oximetry and supplemental oxygen indicated in acute myocardial infarction (MI, heart attack)?

What is the recommended dosage of aspirin in the treatment of acute coronary syndrome (ACS), and which form of aspirin is preferred?

What are nitrates, how are they used in the treatment of acute myocardial infarction (MI, heart attack), and what is the recommended dosage?

What is the recommended dosage of nitrates when chest pain persists or recurs?

When are nitrates contraindicated in patients with symptoms of acute coronary syndrome (ACS)?

What is the drug of choice for the treatment of refractory or severe pain associated with myocardial infarction (MI, heart attack), what is the recommended dosage, and which vital signs must be monitored?

Which analgesics are contraindicated in the treatment of refractory or severe pain in myocardial infarction (MI, heart attack)?

What are the essential components of STEMI management, and which treatment option is emphasized in current clinical guidelines?

Which aspects of emergency intervention are key in shortening total ischemic time in ST-elevation myocardial infarction (STEMI) (MI, heart attack)?

When are early mechanical intervention (primary PCI) and early reperfusion strategies indicated in the treatment of acute coronary syndrome (ACS)?

How readily available are primary PCI services, and how can emergency medical personnel ensure access by patients with myocardial infarction (MI, heart attack)?

What is the management approach to ST-elevation myocardial infarction (STEMI) (MI, heart attack) in a hospital with, and a hospital without, primary percutaneous coronary intervention (PCI)?

What is percutaneous coronary intervention (PCI), and what is its role in the treatment of ST-elevation myocardial infarction (STEMI) (MI, heart attack)?

What are the guidelines for performing PCI in the treatment of ST-elevation myocardial infarction (STEMI) (MI, heart attack)?

How does PCI accomplish reperfusion, and what is the role of stents in PCI?

How can cardiac rupture be predicted during primary PCI for treatment of ST-segment elevation myocardial infarction (MI) (STEMI)?

What is fibrinolysis, and when is it indicated in the treatment of ST-elevation myocardial infarction (STEMI) (MI, heart attack)?

What adverse effect is associated with fibrinolytic therapy, and which patients are at greatest risk?

Which fibrinolytic agents are available for the management of ST-elevation myocardial infarction (STEMI) (MI, heart attack)?

What is the role of coronary artery bypass grafting (CABG) in the acute management of ST-elevation myocardial infarction (STEMI) (MI, heart attack)?

What is the role of anticoagulant therapy in the acute management of ST-elevation myocardial infarction (STEMI) (MI, heart attack), and what are the available options?

How is anticoagulation used in patients receiving fibrinolytic therapy for the treatment of ST-elevation myocardial infarction (STEMI) (MI, heart attack)?

What is the role of aspirin in the treatment of ST-elevation myocardial infarction (STEMI) (MI, heart attack), and which other agents are used for dual antiplatelet therapy?

Which antiplatelet agents are used in patients undergoing primary PCI for ST-elevation myocardial infarction (STEMI) (MI, heart attack)?

How are antiplatelet agents used in patients receiving fibrinolytic therapy for ST-elevation myocardial infarction (STEMI) (MI, heart attack)?

In addition to clopidogrel, which other antiplatelet agents may be used in ST-elevation myocardial infarction (STEMI) (MI, heart attack) management?

What is ticagrelor, and what is its role in the treatment of non-ST-elevation acute coronary syndrome (unstable angina and NSTEMI)?

What is the role of glycoprotein (GP) IIb/IIIa receptor inhibitors in the treatment of non-ST-elevation acute coronary syndrome (unstable angina and NSTEMI), and which agents are preferred?

What is the dosage regimen of bivalirudin in the treatment of non-ST-elevation acute coronary syndrome (unstable angina and NSTEMI)?

What are the key points of managing non-ST-elevation acute coronary syndrome (unstable angina and NSTEMI), and what are the alternative management strategies?

Which patients with non-ST-elevation acute coronary syndrome (unstable angina and NSTEMI) are candidates for an early invasive management strategy?

How do beta blockers work, and how are they used in the treatment of non-ST-elevation acute coronary syndrome (unstable angina and NSTEMI)?

When are beta blockers contraindicated in the treatment of non-ST-elevation acute coronary syndrome (unstable angina and NSTEMI)?

When are non-dihydropyridine calcium channel blockers indicated in the treatment of non-ST-elevation acute coronary syndrome (unstable angina and NSTEMI)?

Which antiplatelet agent is preferred in non-ST-elevation acute coronary syndrome (unstable angina and NSTEMI), and what is the recommended dosage?

What are the benefits of P2Y12 receptor inhibitors in the management of myocardial infarction, and which are most commonly used in the treatment of non-ST-elevation acute coronary syndrome (unstable angina and NSTEMI)?

What is the treatment regimen for clopidogrel, and when is it indicated in the treatment of non-ST-elevation acute coronary syndrome (unstable angina NSTEMI)?

What is the dosage regimen of prasugrel in the treatment of non-ST-elevation acute coronary syndrome (unstable angina and NSTEMI), and when is it contraindicated?

Which patients with non-ST-elevation acute coronary syndrome (unstable angina and NSTEMI) should receive anticoagulant therapy?

What is the dosage regimen for unfractionated heparin (UH) in the treatment of non-ST-elevation acute coronary syndrome (unstable angina and NSTEMI), and what is its disadvantage?

What is the dosage regimen of low molecular weight heparin (LMWH) in the treatment of non-ST-elevation acute coronary syndrome (unstable angina and NSTEM), and what are the benefits and risks of enoxaparin?

What is dosage regimen of fondaparinux in the treatment of non-ST-elevation acute coronary syndrome (unstable angina and NSTEMI), and when is it contraindicated?

What are the goals of management after the initial treatment and stabilization of acute myocardial infarction (MI, heart attack)?

What are the roles of ACE inhibitors, ARBs, and aldosterone blockers in the treatment of acute myocardial infarction (MI, heart attack)?

What are the guidelines for the use of beta blockers in long-term treatment after acute myocardial infarction (MI, heart attack)?

What are the current clinical practice guidelines for the use of long-term statin therapy in acute myocardial infarction (MI, heart attack)?

Which lifestyle modifications are associated with a reduction in recurrent myocardial infarction (MI, heart attack) and prevention of further progression of cardiovascular disease?

Which rehabilitation programs should be offered to patients with myocardial infarction (MI, heart attack)?

What are the special considerations in treating elderly patients with myocardial infarction (MI, heart attack)?

What are the complications of myocardial infarction (MI, heart attack)?

What is the incidence of cardiac arrhythmias in patients with acute myocardial infarction (MI, heart attack), and what treatment is indicated?

What are the major mechanical complications of myocardial infarction (MI, heart attack)?

What is a left ventricular aneurysm, and what are the risk factors for these aneurysms after acute myocardial infarction (MI, heart attack)?

When do ventricular septal ruptures occur in the setting of acute myocardial infarction (MI, heart attack), and which patients are at greatest risk for this complication?

How can morbidity and mortality associated with ventricular septal rupture be avoided?

Where do ventricular ruptures occur, and which interventions are essential to survival?

How common does right ventricular infarction complicate inferior myocardial infarction (MI), and how is it diagnosed?

What is the presentation of ventricular infarction in patients with myocardial infarction (MI, heart attack), which interventions are indicated, and which medications are contraindicated?

How are complications of myocardial infarction (MI, heart attack) diagnosed, and how is pseudoaneurysm differentiated from a true aneurysm on imaging?

What is the incidence of left ventricular mural thrombus in the setting of acute anterior myocardial infarction (MI, heart attack), and what are the associated risks and treatment?

What are the incidence and clinical presentation of early pericarditis after myocardial infarction (MI, heart attack)?

What future and emerging therapies exist for the treatment of myocardial infarction (MI, heart attack)?

Guidelines

What are the guidelines for prehospital and emergency care in patients with ST-elevation myocardial infarction (STEMI) (MI, heart attack)?

What is the recommended reperfusion strategy for patients with ST-elevation myocardial infarction (STEMI) (MI, heart attack) and symptom onset within the preceding 12-24 hours?

What are the 2013 ACC/AHA guidelines for PCI after administration of fibrinolytic therapy in the treatment of ST-elevation myocardial infarction (STEMI) (MI, heart attack)?

What are the treatment guidelines for PCI in ST-elevation myocardial infarction (STEMI) (MI, heart attack)?

What are the 2015 ACC/AHA/SCAI treatment guidelines for percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI) (MI, heart attack)?

What are the 2017 ESC treatment guidelines for percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI) (MI, heart attack)?

What are the 2011 ACC/AHA/SCAI treatment guidelines for percutaneous coronary intervention (PCI) and bare-metal stents (BMS) or drug-eluting stents (DES) for myocardial infarction (MI, heart attack)?

What are the 2014 ESC/EACTS and 2017 ESC guidelines regarding the use of drug-eluting stents (DES) in percutaneous coronary intervention (PCI) for the treatment of myocardial infarction (MI, heart attack)?

What are the 2013 ACC/AHA guidelines for antithrombotic therapy in patients undergoing primary PCI for ST-elevation myocardial infarction (STEMI) (MI, heart attack)?

What are the 2014 ACC/AHA guidelines for coronary artery bypass grafting (CABG) in the treatment of ST-elevation myocardial infarction (STEMI) (MI, heart attack)?

What are the 2014 ACC/AHA guidelines for coronary artery bypass grafting (CABG) after failed percutaneous coronary intervention (PCI) in the treatment of myocardial infarction (MI, heart attack)?

What are the 2015 AHA guidelines for secondary prevention after coronary artery bypass grafting (CABG)?

What are the 2015 SCAI/ACC/HFSA/STS guidelines for mechanical circulatory support (MCS) devices in the treatment of myocardial infarction (MI, heart attack)?

According to the 2013 ISHLT guidelines for acute cardiogenic shock, when is mechanical circulatory support (MCS) indicated in the treatment of myocardial infarction (MI, heart attack)?

According to the 2016 ACC/AHA guidelines, which medications should be included in a dual antiplatelet therapy (DAPT) regimen in the treatment of myocardial infarction (MI, heart attack)?

What are the 2016 ACC/AHA guidelines for the use of dual antiplatelet therapy (DAPT) in non-ST-elevation acute coronary syndrome (NSTE-ACS) or ST-elevation myocardial infarction (STEMI) (MI, heart attack)?

Which P2Y12 inhibitor is preferred in non-ST-elevation acute coronary syndrome (NSTE-ACS) or ST-elevation myocardial infarction (STEMI), according to the 2016 ACC/AHA guidelines on duration of dual antiplatelet therapy (DAPT)?

According to the 2016 ACC/AHA guidelines on dual antiplatelet therapy (DAPT), when is treatment continued for more than a year, and when is treatment stopped after 6 months in NSTE-ACS or STEMI?

According to the 2016 ACC/AHA guidelines on dual antiplatelet therapy (DAPT), when is prasugrel contraindicated in coronary artery disease (CAD)?

Medications

What are the goals of pharmacotherapy for myocardial infarction (MI, heart attack), and what are the goals of emergency department medical therapy for MI?

Which medications in the drug class Antiplatelet Agents are used in the treatment of Myocardial Infarction?

Which medications in the drug class Antithrombotic Agents are used in the treatment of Myocardial Infarction?

Which medications in the drug class Glycoprotein IIb/IIIa Inhibitors are used in the treatment of Myocardial Infarction?

Which medications in the drug class Vasodilators are used in the treatment of Myocardial Infarction?

Which medications in the drug class Beta-adrenergic blockers are used in the treatment of Myocardial Infarction?

Which medications in the drug class Angiotensin-Converting Enzyme Inhibitors are used in the treatment of Myocardial Infarction?

Which medications in the drug class Angiotensin-Receptor Blockers are used in the treatment of Myocardial Infarction?

Which medications in the drug class Thrombolytics are used in the treatment of Myocardial Infarction?

Which medications in the drug class Analgesics are used in the treatment of Myocardial Infarction?

Which medications in the drug class PCSK9 Inhibitors are used in the treatment of Myocardial Infarction?