Introduction
The key principles that underlie management of myocardial infarction (MI) are based on the pathophysiology of the condition and the time course of irreversible myocardial injury. The fundamental goals of managing acute MI include (1) minimizing the duration of exposure of myocardium to ischemia, (2) rapidly establishing effective reperfusion, (3) preventing recurrent ischemia and re-occlusion, (4) managing arrhythmic and mechanical complications, and (5) modifying underlying atherosclerosis toward the aim of long-term secondary prevention ( Figure 13-1 ). The targets for therapy are the molecular, cellular, and anatomic features in the onset, evolution, and complications of MI.
The most prevalent precursor of MI is rupture or erosion of an atheromatous plaque in the coronary artery, with thrombotic occlusion and embolization of thrombotic fragments into the distal territory of the affected coronary artery (type 1 MI), together with changes in vascular tone ( Figure 13-2 and 
; also see Chapter 3 ). Oxygen supply–demand imbalance can also lead to infarction (type 2 MI) without coronary occlusion. The management of type 2 MI focuses on correction of the cause of the imbalance (e.g., anemia, tachycardia, heart failure). These pathobiological insights form the basis for therapies aimed at contributors to coronary thrombosis at the time of presentation (see the section on Emergency In-Hospital Management ), during the initial hospitalization (see the section on Recurrent Ischemia ), and over the long-term (see the section on Secondary Prevention and Rehabilitation ).
The clinical manifestations and complications of MI are dependent on the extent and duration of ischemia and the volume of myocardium affected. This tight temporal relationship with outcomes frames the initial management objectives for acute MI (see the sections on Prehospital Management and Emergency In-Hospital Management ) and the importance of developing systems of care that achieve these objectives (see Chapter 5 ). Acute myocardial ischemia may manifest clinically as ST-elevation MI (STEMI), as non–ST-elevation MI (NSTEMI), or if there is no detectable injury, as unstable angina (see Chapter 1 ). Despite substantial progress in the acute management of STEMI, approximately 15% to 20% of patients still present too late for reperfusion (especially older adults and those with major comorbidities), and internationally, many healthcare systems fail to achieve the standards set out in professional guidelines (see the section on Early Recognition of Myocardial Infarction ). However, multiple reports demonstrate that the guideline targets are achievable and are associated with improved cardiovascular outcomes after STEMI. Prompt reperfusion of a greater proportion of eligible STEMI patients would achieve greater overall healthcare gains than have been made possible by incremental advances in hospital care (e.g., emergence of newer reperfusion strategies).
This chapter provides an overview of these essential general principles of managing acute MI, including initial reperfusion, as well as the ischemic, thrombotic, electrical, and mechanical complications of MI. The chapter constructs a scaffold on which the subsequent chapters in this section build the details of treatment. The pathobiology of atherothrombosis, ischemic injury, myocardial healing, and remodeling are described in Chapter 3 , Chapter 4 , Chapter 36 , respectively. The diagnosis of MI is discussed in Chapter 6 and Chapter 7 .
Prehospital Management
Early Recognition of Myocardial Infarction
Key challenges in the early management of MI require recognition by the patient that the symptoms merit emergency evaluation, and then actions that lead to prompt presentation to emergency medical systems (together this interval constitutes “patient delay”) ( Box 13-1 and Figure 14-1 ). Some patients experience prodromal unstable angina followed by progression to infarction (with or without complete coronary occlusion). Many patients fail to recognize the symptoms of MI and may delay presentation because of atypical symptoms, or fear and denial that they are experiencing a heart attack. Public awareness campaigns can trigger a spate of false alarms in the short term, but improved public education has led to a shortening of the time to presentation in many healthcare systems. Women tend to present later than men, as well as older adults, some ethnic groups (e.g., Hispanics, African Americans, those of South Asian ancestry), and the socioeconomically disadvantaged. Patients presenting with MI for the second time tend to delay more than first presenters, implicating a possible role of denial and fear.
Early Recognition of Myocardial Infarctions
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Public education challenges: “false alarms;” slow responders, including older adults, the frail, certain ethnic groups; slower responses among women versus men.
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Availability of rapid response emergency medical systems with integrated cardiac networks of care and direct access to “Heart Attack (percutaneous coronary intervention [PCI] capable) Centers.”
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ST-elevation myocardial infarction (STEMI): avoiding interhospital transfers; prehospital diagnosis (e.g., electrocardiography telemetry to cardiac center); bypassing hospitals without direct PCI capability unless none available.
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STEMI: prehospital fibrinolysis if no PCI-capable hospital is <60 min away.
Prehospital approaches to facilitate rapid diagnosis of MI once the patient has made a first medical contact are described in Chapter 5 .
Cardiac Arrest
Epidemiological studies demonstrate that 60% to 73% of deaths associated with STEMI occur out of hospital, mainly within the first 1 to 2 hours after onset. These early deaths are mainly the result of cardiac arrest caused by ventricular fibrillation. Interrupting the link between acute MI and sudden cardiac death is a critical goal in the management of MI ( Box 13-2 ). Despite major advances in in-hospital care of MI, there is little evidence for a decline in the rates of prehospital mortality. However, ongoing initiatives in many communities are aiming to address this deficiency; for example, Chain of Survival campaigns, which promote the availability of trained individuals to initiate cardiopulmonary resuscitation (CPR) and to use automatic external defibrillators, are designed to reduce prehospital mortality caused by cardiac arrest (see Chapter 5 ). Educational initiatives have increased awareness of CPR and have increased the proportion of patients with cardiac arrest receiving CPR. For patients successfully resuscitated after ventricular fibrillation complicating MI, current guidelines recommend emergency angiography and prompt primary percutaneous revascularization.
Sudden Cardiac Death and Resuscitation
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Prehospital cardiac arrests and sudden deaths account for most early deaths from acute myocardial infarction.
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Success of resuscitation is critically time dependent (after each minute of ventricular fibrillation survival diminishes 7%–10%).
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Bystander cardiopulmonary resuscitation (CPR) increases survival by approximately 30%.
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Regions with well-developed CPR training and availability of automated external defibrillators (AEDs) have two- to three-fold greater survival rates from out-of-hospital cardiac arrests.
Systems Development for Rapid Reperfusion
Governmental health systems, professional societies, hospitals, and individual providers for patients with MI have focused substantial attention on in-hospital delays (door-to-needle or door-to-balloon time); yet, prehospital delays are the largest contributor to ischemic time. Therefore, systems-based approaches are needed to deliver effective integrated management with shortened overall ischemic time. The overall systems goal of limiting ischemic time (ideally ≤120 minutes), challenges in meeting current targets, and operational approaches to achieve these goals are discussed comprehensively in Chapter 5 . Development of well-organized systems for MI care is possible, and achievement of such targets for time to treatment are realistic. In this context, comprehensive national and international registries (e.g., GRACE) have demonstrated important temporal trends of diminishing mortality and decreasing incidence of new-onset heart failure (see Chapter 2 ).
Emergency In-Hospital Management
The emergency management of patients with suspected MI is rooted in rapid diagnosis and swift restoration of flow in the culprit artery. Critical concepts in the emergency management of MI are listed in Box 13-3 and reviewed in the following section. The initial diagnostic assessment of patients with suspected acute MI is discussed in Chapter 6 , and the related use of cardiac biomarkers and imaging methods are detailed in Chapter 7 , Chapter 8 , Chapter 9 .
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Reperfusion and revascularization are critical to reduce ischemic time.
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The goals include: emergency medical service response times within <10 min, transfer to percutaneous coronary intervention capable center <30 min, first medical contact to reperfusion <90 min.
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Electrocardiography telemetry and bypassing of emergency room for confirmed myocardial infarction.
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Prehospital fibrinolysis if transfer times prolonged.
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Adjunctive therapies to reduce recurrent ischemia and to manage arrhythmias and heart failure.
Rapid Reperfusion
Minimizing the delay to reperfusion in patients with STEMI is critical to salvage ischemic myocardium, to limit residual injury, to reduce the risk of subsequent heart failure, and to improve survival (see Chapter 14 and Chapter 36 ). The impact of time delay is not linear ( Figure 13-3 ); the most effective salvage of myocardium is achieved with reperfusion within 60 to 90 minutes of ischemic onset. The term “golden hour” has been applied to the first 60 minutes of infarction because restoring myocardial function is best achieved within this period, and some patients even experience aborted infarction without evolving electrocardiographic (ECG) changes of MI and without measurable mechanical deficit (see Figure 13-3 ).
The clinical manifestations of MI are a function of the severity and duration of ischemia and the consequent volume of myocardium with irreversible cellular injury. Therefore, the initial care of the patient with STEMI is targeted at initiating therapy to restore flow in the infarct-related artery as rapidly as possible. The selection of the approach to reperfusion therapy, including the choice of administration of a fibrinolytic agent versus primary percutaneous coronary intervention (PCI), and related decisions regarding interhospital transfer, are addressed in Chapter 14 . Fibrinoytic therapy for STEMI is discussed comprehensively in Chapter 15 , and the approach to primary PCI is detailed in Chapter 17 .
Although more attention has focused on the timing of reperfusion in patients with STEMI, patients with NSTEMI may also develop major complications, including heart failure, hypotension, and arrhythmias as a consequence of prolonged ischemia. Patients with NSTEMI, particularly those at high risk, should also be considered for emergency revascularization to resolve ongoing or intermittent ischemia (see the section on Initial Risk Assessment and Chapter 16 ).
Fibrinolysis
Administration of a fibrinolytic agent was the cornerstone of reperfusion therapy before the development of primary PCI, and still constitutes important therapy in settings where primary PCI is not available or not available expeditiously (see Chapter 14 ). The oldest fibrinolytic agents (streptokinase and urokinase) are still widely used in some parts of the world because of cost. Subsequent evolution of fibrinolytic therapy has aimed to improve ease and rapidity of administration, as well as the balance of fibrinolytic efficacy versus bleeding. In comparison to streptokinase, later generation fibrinolytics, including alteplase, reteplase, and tenecteplase, have amplified effects at the sites of thrombus formation (see Chapter 15 ).
Despite the similarities in the early mechanisms of STEMI and acute coronary syndromes (ACSs) without ST-elevation, and the key role of thrombosis in both, fibrinolysis failed to demonstrate benefit in early studies of the treatment of unstable angina. Because those studies included low-risk patients, some experts have questioned whether there could be a role for coronary administration of modern fibrinolytic agents in high-risk NSTEMI. Nevertheless, because of the absence of established benefit and a clear increased risk of serious bleeding, professional society guidelines do not recommend administration of fibrinolytic agents to patients with NSTEMI.
Pathways of Care: ST-Elevation Myocardial Infarction
Pathways of care for patients with STEMI are aimed at minimizing the duration of ischemia and triage of patients to the optimal environment for management of the complications of MI (see Chapter 5 ). Timely primary PCI is preferred whenever it is available and provided by experienced STEMI teams, and has become the dominant approach to reperfusion therapy in most countries ( Figure 13-4 ). Critical elements of pathways of care for STEMI include prompt recognition by the patient of the need to call emergency medical systems, rapid dispatch and arrival of emergency providers (<10 minutes), in-ambulance diagnosis of suspected STEMI, administration of analgesia and antithrombotic agents, rapid transfer to a PCI-capable center (<30 minutes), and mobilization for timely PCI ( Figure 13-5 ). Direct admission to the catheterization laboratory avoids the delays involved in emergency department evaluation. When prehospital transfers are prolonged because of distance from the PCI center, or traffic and adverse weather, the option of prehospital administration of fibrinolysis is needed (see Chapter 14 ). Even after apparently successful fibrinolysis, transfer to a PCI-capable center is needed to treat the underlying stenosis, to minimize risks of re-occlusion, and to consider revascularization of nonculprit coronary stenoses (see the section on Recurrent Ischemia and Chapter 14 ).
Pathways of Care: Non–ST-Elevation Myocardial Infarction
The clinical presentation of NSTEMI is more insidious than that of STEMI and may be preceded by new-onset exertional angina, deteriorating or unstable angina, or no previous symptoms. Unlike STEMI, autonomic features do not usually accompany the onset of NSTEMI. Because of the pattern of onset, the patient may misinterpret the symptoms as gastrointestinal or musculoskeletal in nature, and presentation is frequently to nonemergency medical services (primary care or internal medicine, or to nonemergency chest pain clinics). The diagnosis is based on the clinical syndrome plus ECG findings of ischemia, but without persistent ST-elevation (see Chapter 1 and Chapter 6 ) and sensitive biomarkers of necrosis (e.g., high-sensitivity troponin; see Chapter 7 ). However, the diagnosis can be challenging in the presence of minor nonspecific ECG abnormalities and biomarkers of necrosis that may be elevated by supply–demand imbalance (type 2 MI) or myocyte necrosis in the absence of coronary occlusion (e.g., in heart failure or pulmonary embolism). Particular care is needed to identify patients with evolving infarction but who do not have ST-elevation at the time of first presentation. Repeated ECG analysis or continuous ST monitoring is important for this reason. Once the diagnosis of NSTEMI is established, antithrombotic therapies should be initiated while consideration of invasive evaluation is undertaken (see the section on Initial Risk Assessment ).
Other Medical Therapy at Presentation
A schematic overview of the management of MI is provided in Figure 13-6 . The rationale for use of anticoagulant and antiplatelet agents are addressed later in this chapter, as are agents to mitigate myocardial oxygen supply–demand mismatch (see the section on Recurrent Ischemia ).
Analgesics
Relief of pain is important, not only to relieve distress, but also to avoid the consequences of sympathetic simulation on the heart, including increases in afterload and arrhythmogenesis (see Chapter 28 ). Intravenous opioid analgesia is the most commonly used therapy and should be carefully titrated, and is often administered with antiemetics. For example, intravenous morphine sulfate at a dose of 2 to 8 mg repeated at intervals of 5 to 15 minutes has been recommended, until the pain is relieved or side effects (e.g., hypotension, depression of respiration, or severe vomiting) emerge. The reduction of anxiety with successful analgesia diminishes the patient’s restlessness and the activity of the autonomic nervous system, with a consequent reduction of the heart’s metabolic demands. Morphine may also provide favorable effects in patients with pulmonary edema caused by peripheral arterial and venous dilation, reduction of the work of breathing, and slowing of heart rate secondary to combined withdrawal of sympathetic tone and augmentation of vagal tone. Observational studies have identified an association between administration of morphine and adverse outcomes in patients with ACS; however, it is challenging to disentangle this observation from confounding by indication.
Nitrates
Nitrates are commonly given in acute MI, and they may relieve vasospasm and reduce pain. By virtue of their ability to enhance coronary blood flow by coronary vasodilation and to decrease ventricular preload by increasing venous capacitance, sublingual nitrates have been recommended for the initial treatment of patients with MI. At present, the only groups of patients with STEMI in whom sublingual nitroglycerin should not be given are those with suspected right ventricular infarction or marked hypotension (e.g., systolic pressure <90 mm Hg), especially if accompanied by bradycardia. The patient should be observed for improvement in symptoms or change in hemodynamics. Even small doses can produce sudden hypotension and bradycardia, a reaction that can usually be reversed with intravenous atropine. Long-acting oral nitrate preparations should be avoided in the early course of STEMI because of the frequently changing hemodynamic status of the patient. In patients with a prolonged period of waxing and waning chest pain, intravenous nitroglycerin may help to control symptoms and correct ischemia, but requires frequent monitoring of blood pressure. Initiation of a reperfusion strategy in patients with STEMI should not be delayed while assessing the patient’s response to sublingual or intravenous nitrates. Despite the strong pathobiological rationale, administration of nitrates has not been shown to improve clinical outcomes compared with placebo in patients with MI (see the section on Other Medical Therapies to Reduce Ischemia ).
Oxygen
Treating all patients hospitalized with MI with oxygen for at least 24 to 48 hours is common practice on the basis of the empirical assumption of hypoxia and evidence that increased oxygen in the inspired air may protect ischemic myocardium. However, the evidence to support its use in those without heart failure or hypoxia is lacking. In patients with hypoxia (oxygen saturation below ∼94%), hypoxia can be corrected by oxygen delivery using a face mask. However, for those with more profound hypoxia associated with heart failure, ventilation and circulation support may be required (see Chapter 25 ). Conversely, in a small study comparing oxygen and air administration for those with oxygen saturations more than 94%, there was no evidence of benefit and a trend toward harm (6-month infarct size) in those given supplemental oxygen.
Recurrent Ischemia
Complete and durable relief of ischemia, alleviation of symptoms, and prevention of recurrent coronary thrombotic complications are core management goals for the care of patients with MI ( Box 13-4 ). Early recurrent ischemia and reinfarction are important complications of acute MI; although their rate has declined with routine coronary revascularization (see Chapter 23 ). Fibrinolysis is an option for initial dissolution of completely obstructive thrombus in patients with STEMI, if timely primary PCI is not available (see the section on Rapid Reperfusion and Chapter 15 ). Antiplatelet and anticoagulant therapy are important to reduce the extension of thrombus or reocclusion, and coronary revascularization is critically important to relieve coronary artery obstruction. These are the mainstays of therapy to address coronary occlusions in most patients with STEMI. For patients with NSTEMI and patients with STEMI who have residual coronary disease after culprit vessel reperfusion, therapies to improve myocardial oxygen supply–demand mismatch are a cornerstone of therapy and are used in conjunction with antithrombotic therapy ( Figure 13-7 ). Because of the risks of progression of infarction and the development of complications, including heart failure, arrhythmias, and cardiogenic shock, with ongoing or recurrent ischemia, management by a team with ACS expertise and appropriate facilities is necessary. Careful and systematic assessment of the risk of death and recurrent ischemic events is central to the appropriate selection of management strategies and triage to the best care environment (see also Chapter 11 ).
