myocardial infarction

Myocardial Infarction

Article Last Updated: Sep 10, 2007

AUTHOR AND EDITOR INFORMATION

Section 1 of 11

Author: Drew E Fenton, MD, Family Practice Physician, Ocean Medical Family and Urgent Care

Drew E Fenton is a member of the following medical societies: American Academy of Emergency Medicine

Editors: Robert M McNamara, MD, FAAEM, Professor of Emergency Medicine, Temple University; Chief, Department of Internal Medicine, Section of Emergency Medicine, Temple University Hospital; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Gary Setnik, MD, Chair, Department of Emergency Medicine, Mount Auburn Hospital; Assistant Professor, Division of Emergency Medicine, Harvard Medical School; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; Craig Feied, MD, FACEP, FAAEM, FACPh, Professor of Emergency Medicine, Georgetown University; Director, National Institute for Medical Informatics; Director, Federal Project ER One; Director, National Center for Emergency Medicine Informatics

Author and Editor Disclosure

Synonyms and related keywords: MI, acute myocardial infarction, AMI, heart attack, myocardial necrosis, thrombus, atherosclerotic plaque, atheromatous plaques, platelet aggregation, vasospasm, ischemic heart disease, hypercholesterolemia, hypertriglyceridemia, chest pain, dyspnea, lightheadedness, syncope, fatigue, diaphoresis, hypertension, mitral regurgitation, dysrhythmias, acute valvular dysfunction, congestive heart failure, CHF, neck vein distention, rales, third heart sound, fourth heart sound, heart block, emboli, right ventricular failure, cannon jugular venous a waves, left ventricular hypertrophy, LVH, idiopathic hypertrophic subaortic stenosis, IHSS, coronary artery vasospasm, smoking, diabetes mellitus, acute coronary syndrome

INTRODUCTION

Section 2 of 11

Background

Myocardial infarction (MI) is the rapid development of myocardial necrosis caused by a critical imbalance between oxygen supply and demand of the myocardium. This usually results from plaque rupture with thrombus formation in a coronary vessel, resulting in an acute reduction of blood supply to a portion of the myocardium.

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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 clinically unrecognized, evidencing that patients and physicians often do not recognize symptoms of a MI. The appearance of cardiac markers in the circulation generally indicates myocardial necrosis and is a useful adjunct to diagnosis.

Cardiac markers help to categorize MI, which is considered part of a spectrum referred to as acute coronary syndrome that includes ST-elevation MI (STEMI), non–ST-elevation MI (NSTEMI), and unstable angina. This categorization is valuable because patients with ischemic discomfort may or may not have ST-segment elevations on their electrocardiogram. Those without ST elevations may ultimately be diagnosed with NSTEMI or with unstable angina based on the presence or absence of cardiac enzymes. Additionally, therapeutic decisions, such as administering an intravenous thrombolytic or performing percutaneous coronary intervention (PCI), are often made based on this categorization.

Pathophysiology

The most common cause of MI is narrowing of the epicardial blood vessels due to atheromatous plaques. Plaque rupture with subsequent exposure of the basement membrane results in platelet aggregation, thrombus formation, fibrin accumulation, hemorrhage into the plaque, and varying degrees of vasospasm. This can result in partial or complete occlusion of the vessel and subsequent myocardial ischemia. Total occlusion of the vessel for more than 4-6 hours results in irreversible myocardial necrosis, but reperfusion within this period can salvage the myocardium and reduce morbidity and mortality.

Nonatherosclerotic causes of MI include coronary vasospasm as seen in variant (Prinzmetal) angina and in patients using cocaine and amphetamines; coronary emboli from sources such as an infected heart valve; occlusion of the coronaries due to vasculitis; or other causes leading to mismatch of oxygen supply and demand, such as acute anemia from GI bleeding. MI induced by chest trauma has also been reported, usually following severe chest trauma such as motor vehicle accidents and sports injuries. For additional information, see Medscape's article "New Definition of 'MI' Poised for World Domination".

Frequency

United States

MI is a leading cause of morbidity and mortality in the United States. Approximately 1.3 million cases of nonfatal MI are reported each year, for an annual incidence rate of approximately 600 cases per 100,000 people. The proportion of patients diagnosed with NSTEMI compared with STEMI has progressively increased.

International

Cardiovascular diseases account for 12 million deaths annually worldwide. MI continues to be a significant problem in industrialized countries and is becoming an increasingly significant problem in developing countries.

Mortality/Morbidity

Approximately 500,000-700,000 deaths are caused by ischemic heart disease annually in the United States.

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One third of patients who experience STEMI die within 24 hours of the onset of ischemia, and many of the survivors experience significant morbidity. For many patients, the first manifestation of coronary artery disease is sudden death likely from malignant ventricular dysrhythmia.

More than one half of deaths occur in the prehospital setting. In-hospital fatalities account for 10% of all deaths. An additional 10% of deaths occur in the first year

postinfarction. A steady decline has occurred in the mortality rate from STEMI over the last several decades. This

appears to be due to a combination of a fall in the incidence of MI (replaced in part by an increase in the incidence of unstable angina) and a reduction in the case-fatality rate once an MI has occurred.

Sex

A male predilection exists in persons aged 40-70 years. Evidence exists that women more often have MIs without atypical symptoms. The atypical presentation in women might explain the sometimes delayed diagnosis of MIs in women.

In persons older than 70 years, no sex predilection exists.

Age

MI most frequently occurs in persons older than 45 years.

Certain subpopulations younger than 45 years are at risk, particularly cocaine users, persons with type 1 diabetes mellitus, patients with hypercholesterolemia, and those with a positive family history for early coronary disease. A positive family history includes any first-degree male relative aged 45 years or younger or any first-degree female relative aged 55 years or younger who experienced a myocardial infarction. In younger patients, the diagnosis may be hampered if the physician does not maintain a high index of suspicion.

CLINICAL

Section 3 of 11

History

The history is critical in making the diagnosis of MI and sometimes may provide the only clues that lead to the diagnosis in the initial phases of the patient presentation.

Chest pain, usually across the anterior precordium is typically described as tightness, pressure, or squeezing.

Pain may radiate to the jaw, neck, arms, back, and epigastrium. The left arm is more frequently affected; however, a patient may experience pain in both arms.

Dyspnea, which may accompany chest pain or occur as an isolated complaint, indicates poor ventricular compliance in the setting of acute ischemia. Dyspnea may be the patient's anginal equivalent, and, in an elderly person or a patient with diabetes, it may be the only complaint.

Nausea, abdominal pain, or both often are present in infarcts involving the inferior or posterior wall.

Anxiety Lightheadedness with or without syncope Cough Nausea with or without vomiting Diaphoresis Wheezing Elderly patients and those with diabetes may have particularly subtle presentations and may complain of

fatigue, syncope, or weakness. The elderly may also present with only altered mental status. Those with preexisting altered mental status or dementia may have no recollection of recent symptoms and may have no complaints whatsoever.

As many as half of MIs are clinically silent in that they do not cause the classic symptoms described above and consequently go unrecognized by the patient. A high index of suspicion should be maintained for MI especially when evaluating women, patients with diabetes, older patients, patients with dementia, and those with a history of heart failure. Patients with a permanent pacemaker in place may confound recognition of STEMI by 12-lead ECG due to the presence of paced ventricular contractions.

Physical

The physical examination can often be unremarkable.

Patients with ongoing symptoms usually lie quietly in bed and appear pale and diaphoretic. Hypertension may precipitate MI, or it may reflect elevated catecholamine levels due to anxiety, pain, or

exogenous sympathomimetics. Hypotension may indicate ventricular dysfunction due to ischemia. Hypotension in the setting of MI

usually indicates a large infarct secondary to either decreased global cardiac contractility or a right ventricular infarct.

Acute valvular dysfunction may be present. Valvular dysfunction usually results from infarction that involves the papillary muscle. Mitral regurgitation due to papillary muscle ischemia or necrosis may be present.

Rales may represent congestive heart failure. Neck vein distention may represent pump failure. With right ventricular failure, cannon jugular venous a

waves may be noted. Third heart sound (S3) may be present. A fourth heart sound is a common finding in patients with poor ventricular compliance that is due to

preexisting heart disease or hypertension. Dysrhythmias may present as an irregular heartbeat or pulse. Low-grade fever is not uncommon.

Causes

The most frequent cause of MI is rupture of an atherosclerotic plaque within a coronary artery with subsequent arterial spasm and thrombus formation.

Other causes include the following:

Coronary artery vasospasm Ventricular hypertrophy (eg, left ventricular hypertrophy [LVH], idiopathic hypertrophic subaortic

stenosis [IHSS], underlying valve disease)

Hypoxia due to carbon monoxide poisoning or acute pulmonary disorders (Infarcts due to pulmonary disease usually occur when demand on the myocardium dramatically increases relative to the available blood supply.)

Coronary artery emboli, secondary to cholesterol, air, or the products of sepsis Cocaine, amphetamines, and ephedrine Arteritis Coronary anomalies, including aneurysms of the coronary arteries Increased afterload or inotropic effects, which increase the demand on the myocardium Aortic dissection, with retrograde involvement of the coronary arteries Although rare, pediatric coronary artery disease may be seen with Marfan syndrome, Kawasaki disease,

Takayasu arteritis, progeria, and cystic medial necrosis (see Myocardial Infarction in Childhood).

Risk factors for atherosclerotic plaque formation include the following:

Age Male gender Smoking Hypercholesterolemia and hypertriglyceridemia, including inherited lipoprotein disorders Diabetes mellitus Poorly controlled hypertension Type A personality Family history Sedentary lifestyle

DIFFERENTIALS

Section 4 of 11

Acute Coronary SyndromeAnxietyAortic StenosisAsthmaCholecystitis and Biliary ColicCholelithiasisChronic Obstructive Pulmonary Disease and EmphysemaCongestive Heart Failure and Pulmonary EdemaDissection, AorticEndocarditisEsophagitisGastroenteritisMitral RegurgitationMyocarditisPancreatitisPericarditis and Cardiac TamponadePneumothorax, Iatrogenic, Spontaneous and PneumomediastinumPulmonary EmbolismShock, Cardiogenic




















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Other Problems to be Considered

Biliary tract disease Esophageal spasm Gastroesophageal reflux disease Unstable angina

WORKUP

Section 5 of 11

Lab Studies

Troponin is the preferred biomarker for diagnosis.o Troponins have the greatest sensitivity and specificity in detecting MI. The test result is both

diagnostic as well as prognostic of outcome.o Troponin is a contractile protein that normally is not found in serum. It is released only when

myocardial necrosis occurs.o For early detection of myocardial necrosis, sensitivity of this laboratory test is superior to that of

the creatine kinase-MB (CK-MB). Troponin I is detectable in serum 3-6 hours after an AMI and its level remains elevated for 14 days.

o Troponin is also the optimum biomarker for the evaluation of patients with MI who have coexistent skeletal muscle injury.

Creatine kinase–MB level o CK-MB levels begin to rise within 4 hours after injury, peak at 18-24 hours, and subside over 3-

4 days. A level within the reference range does not exclude myocardial necrosis.o Occasionally, very small infarcts can be missed by CK-MB; therefore, a troponin level should be

measured for patients suspected of having had MI who have negative serial CK-MBs. Myoglobin levels

o Myoglobin, a low-molecular-weight heme protein found in cardiac and skeletal muscle, is

released more rapidly from infarcted myocardium than troponin and CK-MB and may be detected as early as 2 hours after MI. Myoglobin levels rise early in the course of MI.

o The marker has high sensitivity but poor specificity. When performed in conjunction with other studies, it may be useful for the early detection of MI.

Complete blood counto CBC is indicated if anemia is suspected as a precipitant. Transfusion with packed red blood cells

may be indicated.o Leukocytosis may be observed within several hours after an AMI. It peaks in 2-4 days and

returns to levels within the reference range within 1 week. Chemistry profile

o Potassium and magnesium levels should be monitored and corrected.

o Creatinine levels must be considered before using an angiotensin-converting enzyme (ACE) inhibitor.

C-reactive protein (CRP) is a marker of acute inflammation. Patients without biochemical evidence of myocardial necrosis but with elevated CRP level are at increased risk of a subsequent ischemic event.

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

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.

Imaging Studies

Chest radiographyo Chest radiography may provide clues to an alternative or complicating diagnosis (eg, aortic

dissection, pneumothorax). Other imaging studies such as a contrast chest CT scan or transesophageal echocardiography should be used to differentiate MI from aortic dissection in patients in whom the diagnosis is in doubt. Stanford type A aortic dissections may dissect in a retrograde fashion causing coronary blockage and dissection, which may result in MI. In one study, 8% of patients with Stanford type A dissections had ST elevation on ECG.

o Chest radiography also reveals complications of MI such as pulmonary edema secondary to heart failure.

Echocardiographyo Use 2-dimensional and M-mode echocardiography when evaluating wall motion abnormalities

and overall ventricular function.o Echocardiography can identify complications of MI (eg, valvular insufficiency, ventricular

dysfunction, pericardial effusion). Technetium-99m sestamibi scan

o Technetium-99m is a radioisotope that is taken up by the myocardium in proportion to the blood

flow and is only minimally redistributed after initial uptake. This allows for time delay between injection of the isotope and imaging.

o It has potential use in identifying infarct in patients with atypical presentations or in patients with ECGs that are not interpretable.

o Normal scan findings are associated with an extremely low risk of subsequent cardiac events. Thallium scanning: Thallium accumulates in the viable myocardium. Perfusion imaging has been used in risk stratification after MI and for measurement of infarct size to

evaluate reperfusion therapies. Novel "hot spot" imaging radiopharmaceuticals that visualize infarction or ischemia are currently undergoing evaluation and hold promise for the future. (See Myocardial Ischemia - Nuclear Medicine and Risk Stratification.)

Recent advances include dual-source 64-slice CT scanning that can do a full scan in 10 seconds and produce high-resolution images that allow fine details of the patient's coronary arteries to be seen. This technology allows for noninvasive and early diagnosis of coronary artery disease and thus earlier treatment before the coronary arteries become more or completely occluded. It allows direct visualization of not only the lumen of the coronary arteries but also plaque within the artery. Dual-source 64-slice CT scanning is being used with intravenous contrast to determine if a stent or graft is open or closed.

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MRI can identify wall thinning, scar, delayed enhancement (infarction), and wall motion abnormalities (ischemia). Currently, this is not a primary diagnostic modality for MI, but coronary artery assessment may be enhanced by magnetic resonance angiography (MRA) in the future.

Other Tests

Electrocardiographyo An ECG should be obtained as soon as possible after presentation to the ED.o Approximately one half of patients have diagnostic changes on their initial ECG.o Because the symptoms of AMI can be subtle or protean, an ECG should be performed on any

patient who is older than 45 years and is experiencing any form of thoracoabdominal discomfort, including new epigastric pain or nausea.

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

o Results that indicate high probability of MI are ST-segment elevation greater than 1 mm in 2 anatomically contiguous leads or the presence of new Q waves.

o Results that indicate intermediate probability of MI are ST-segment depression, T-wave inversion, and other nonspecific ST-T wave abnormalities.

o Results that indicate low probability of MI are normal findings on ECG; however, normal or nonspecific findings on ECG do not exclude the possibility of MI.

o Localization of MI based on distribution of ECG abnormalities is as follows:o

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 >1 in V1 and V2; T-wave changes (ie, upright) in V1, V8, and V9

Procedures

Percutaneous coronary interventions (PCIs) are a group of catheter-based technologies used to establish coronary reperfusion. Angiography provides essential knowledge of the extent of coronary disease and is performed prior to PCI. PCI may then be performed as a primary intervention or as an intervention after thrombolysis failure. Evidence suggests that primary PCI is more effective than thrombolysis and should be performed for confirmed STEMI, new or presumably new left bundle-branch block (LBBB), severe congestive heart failure, or pulmonary edema if it can be performed within 12 hours of symptom onset. Door-to-balloon time should be 90 minutes or less.

o Percutaneous transluminal coronary angioplasty (PTCA) (balloon angioplasty) is the primary

therapeutic modality used at centers where it can provide reperfusion as quickly as fibrinolytic therapy. In other centers, it is used selectively for patients failing to respond to thrombolytics.

o PCI has fewer bleeding complications and recurrent ischemia when compared with thrombolysis. PCI restores coronary artery patency in more than 90% of patients.

o A drawback of PCI is the need for 24-hour availability of an angioplasty suite with the required staff and the availability of backup cardiothoracic capabilities. Primary PCI for STEMI should be

performed at hospitals with readily available cardiothoracic surgery. Readily available may be defined as the ability to transport patients quickly to a hospital with cardiothoracic capabilities.

Coronary artery bypass graft may be indicated based on angiographic findings. Morbidity and mortality from MI are significantly reduced if patients and bystanders recognize

symptoms early, activate the EMS system, and thereby shorten the time to definitive treatment. Trained prehospital personnel can provide life-saving interventions if the patient develops cardiac arrest. The key to improved survival is the availability of early defibrillation. Approximately 1 in every 300 patients with chest pain transported to the ED by private vehicle goes into cardiac arrest en route. Several studies have confirmed that patients with STEMI usually do not call 911; in one study, only 23% of patients with a confirmed coronary event used EMS.

TREATMENT

Section 6 of 11

Prehospital Care

All patients being transported for chest pain should be managed as if the pain were ischemic in origin unless clear evidence to the contrary is established.

If available, an ALS unit should transport patients with hemodynamic instability or respiratory difficulty.

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

The American Heart Association (AHA) protocol can be adopted for use by prehospital emergency personnel. This protocol recommends empirical treatment of patients with suspected STEMI with morphine, oxygen, nitroglycerin, and aspirin.

Specific prehospital care includes the following:o Intravenous access, supplemental oxygen, pulse oximetry o Immediate administration of aspirin en route o Nitroglycerin for active chest pain, given sublingually or by spray o Telemetry and prehospital ECG, if available

EMS protocol should be formulated to strongly consider taking patients with suspected MI/ACS, and certainly patients with STEMI, to facilities capable of PCI if geographically possible.

Prehospital thrombolysis allows eligible patients to receive thrombolysis 30-60 minutes sooner than if treatment were given in the ED; however, prehospital thrombolysis is still under investigation.

Emergency Department Care

For purposes of determining appropriate treatment, viewing MI as part of a spectrum of coronary syndromes is helpful; this spectrum includes (1) STEMI, (2) NSTEMI, and (3) unstable angina. Patients with persistent ST elevation should be considered for reperfusion therapy (thrombolysis or primary PCI.) Those without ST elevation will be diagnosed with either NSTEMI if cardiac marker levels are elevated or with unstable angina if serum cardiac marker levels provide no evidence of myocardial injury. Patients presenting with no ST-segment elevation are not candidates for immediate thrombolytics but should receive anti-ischemic therapy and may be candidates for PCI urgently or during admission. Confirmation of the diagnosis of NSTEMI requires waiting for

the results of cardiac markers. In the case of unstable angina, diagnosis may await further diagnostic studies such as coronary angiography or imaging studies to confirm the diagnosis and to distinguish it from noncoronary causes of chest pain.

The initial focus should be on identifying patients with STEMI. An ECG should be performed and shown to an experienced emergency medicine physician within 10 minutes of ED arrival. If STEMI is present, the decision as to whether the patient will be treated with thrombolysis or primary PCI should be made within the next 10 minutes. The goal for patients with STEMI should be to achieve a door-to-drug time of within 30 minutes and a door-to-balloon time of within 90 minutes. If STEMI is not present, then the workup should proceed looking for unstable angina or NSTEMI and for alternative diagnoses.

Treatment is aimed at (1) restoration of the balance between the oxygen supply and demand to prevent further ischemia, (2) pain relief, and (3) prevention and treatment of complications.

Delays in administration of thrombolysis often occur because of delay in obtaining an ECG, interpretation, lack of immediate availability of thrombolytic agents, and outdated protocols requiring cardiology consultation before thrombolytic treatment.

An ECG should be performed as soon as possible after the patient presents to the ED. The ECG should be hand-delivered to an experienced physician for timely review.

All patients should be placed on telemetry. Two large-bore IVs should be inserted if the EMS has not already completed this. Pulse oximetry should be performed, and appropriate supplemental oxygen should be given (maintain

oxygen saturation >90%). A chest radiograph should be obtained soon after arrival to screen for alternative causes of chest pain

and identify possible contraindications to thrombolysis (eg, aortic dissection). Pharmacologic intervention is likely to include the following:

o Aspirin should be administered immediately if not already taken by the patient at home or

administered by EMS before arrival. Aspirin has been shown to decrease mortality and reinfarction rates after MI. Use clopidogrel (Plavix) in case of aspirin allergy.

o Beta-blocker therapy for heart rate control and resultant decrease of myocardial oxygen demand if not contraindicated. Metoprolol (Lopressor) is the standard and is a selective beta1-adrenergic receptor blocker that decreases automaticity of contractions. Beta-blockers reduce the rates of reinfarction and recurrent ischemia and may also reduce mortality.

o Morphine sulphate may be administered for relief of pain and anxiety. Nitrates are useful for preload reduction and symptomatic relief but have no apparent impact on

mortality rate in MI. Systolic BP <90, HR <60 or >100, and RV infarction are a contraindications to nitrate use. Intravenous nitroglycerin is indicated for relief of ongoing ischemic discomfort, control of hypertension, or management of pulmonary congestion. Nitrates should not be administered to patients who have taken any phosphodiesterase inhibitor for erectile dysfunction within the last 24 hours (extend timeframe to 48 h for tadalafil).

Thrombolytic therapy has been shown to improve survival rates in MI.o Door-to-drug time should be no more than 30 minutes. Thrombolytic therapy administered

within the first 2 hours can occasionally abort MI and dramatically reduce the mortality rate. o The optimal approach is to administer thrombolytics as soon as possible after onset of symptoms

(up to 12 h from symptom onset according to some authors) in patients with ST-segment elevation greater than 1 mm in 2 or more anatomically contiguous ECG leads, new or presumed new left bundle-branch block, or anterior ST depression where posterior infarction is suspected.

With ST-segment elevation, the diagnosis is relatively secured; therefore, initiation of reperfusion therapy should not be delayed for the results of cardiac markers.

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

Administer a platelet glycoprotein (GP) IIb/IIIa-receptor antagonist (eptifibatide, tirofiban, or abciximab), in addition to aspirin and unfractionated heparin, to patients with continuing ischemia or with other high-risk features and to patients in whom PCI is planned. Studies suggest that the addition of intravenous platelet glycoprotein (GP) IIb/IIIa-receptor antagonists to aspirin and heparin improves both early and late outcomes, including mortality, Q-wave MI, need for revascularization procedures, and length of hospital stay.

Despite the traditional use of unfractionated heparin in ST elevation MI for decades, controversy regarding its role continues.

o In patients treated with fibrinolytic therapy, recommendations for heparin therapy depend on the

fibrinolytic agent. Heparin has an established role as an adjunctive agent in patients receiving alteplase, reteplase, or tenecteplase but should not be used with nonselective fibrinolytic agents such as streptokinase and anistreplase.

o Heparin is also indicated in patients undergoing primary PCI. Data are scant with regard to heparin efficacy in patients not receiving thrombolytic therapy in the setting of MI; however, considerable rationale exists for ancillary heparin therapy to inhibit the coagulation cascade.

o Low-molecular-weight heparins (LMWH) are commonly used because of convenient dosing and reliable therapeutic levels, but there have been no definitive trials of LMWH in patients with STEMI to provide a firm basis for recommendations. Low-molecular-weight heparin should not be used as an alternative to unfractionated heparin as ancillary therapy to fibrinolytics in patients aged older than 75 years or in patients with significant renal dysfunction (serum creatinine level >2.5 mg/dL in men or >2 mg/dL in women).

An ACE inhibitor (Captopril) should be given orally within the first 24 hours of STEMI to patients with anterior infarction, pulmonary congestion, or left ventricular ejection fraction (LVEF) less than 40% in the absence of hypotension.

An angiotensin receptor blocker (valsartan or candesartan) should be administered to patients with STEMI who are intolerant of ACE inhibitors and who have either clinical or radiological signs of heart failure or LVEF less than 40%.

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

Use of calcium channel blockers in the acute setting has come into question, with some randomized controlled trials and retrospective studies showing increased adverse effects. Diltiazem and verapamil should be avoided in patients with pulmonary edema or severe left ventricular (LV) dysfunction.

Consultations

Great differences in practice patterns and treatment outcomes exist in different hospital and geographic areas. This is due, at least in part, to the wide variation in the availability of PCI and emergency thoracotomy. One study showed that transferring patients to an invasive-treatment center for PCI is superior to on-site fibrinolysis provided that the transfer can be accomplished within 2 hours. Methods used for reperfusion/revascularization must be based on the resources available in a particular community, and protocols should be worked out in

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advance as a collaborative effort between emergency physicians, internists, cardiologists, and cardiothoracic surgeons.

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

A cardiologist should be consulted for the following:o Patients who may benefit from PCI, including "rescue PCI," with transfer if required, for patients

in whom thrombolysis for STEMI fails to achieve reperfusion o Patients in cardiogenic shock o Patients with hemodynamically significant new or worsening murmur o Patients who are not candidates for thrombolytic intervention because of a contraindication o Intractable angina despite medications o Severe pulmonary congestion o Late presentation (>3 h but no more than 12 h) o Where the diagnosis is in doubt o Note that PCI door-to-balloon time should be less than 90 minutes. o Thoracotomy for coronary artery bypass graft may be indicated if PCI fails. Thoracotomy may

also be necessary for valvular repair or in cases of mechanical complications such as LV rupture.

MEDICATION

Section 7 of 11

The main goals of ED medical therapy are rapid intravenous thrombolysis and/or rapid referral for PCI, optimizing oxygenation, decreasing cardiac workload, and controlling pain.

Drug Category: Antithrombotic agents

These agents prevent the formation of thrombus associated with myocardial infarction and inhibit platelet function by blocking cyclooxygenase and subsequent aggregation. Antiplatelet therapy has been shown to reduce mortality rates by reducing the risk of fatal myocardial infarctions, fatal strokes, and vascular death.

Drug Name Aspirin (Anacin, Bayer Buffered Aspirin, Ecotrin)

Description

Administer as soon as possible. Inhibits cyclooxygenase, which produces thromboxane A2, a potent platelet activator. Early administration has been shown to reduce 35-d mortality rate by 23% compared with placebo. An added mortality benefit exists when used in combination with thrombolytics.

Adult Dose 160-324 mg PO (chewed)

Pediatric Dose Not established

Contraindications

Documented hypersensitivity; vitamin K deficiency; liver damage; hypoprothrombinemia; bleeding disorders; asthma; because of association of aspirin with Reye syndrome, do not use in children (<16 y) with influenza

Interactions

Effects may decrease with antacids and urinary alkalinizing agents; corticosteroids decrease salicylate serum levels; additive hypoprothrombinemic effects and increased bleeding time may occur with coadministration of anticoagulants; may antagonize uricosuric effects of probenecid and increase toxicity of phenytoin and valproic acid; doses >2 g/d may potentiate glucose-lowering effect of sulfonylurea drugs

PregnancyD - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

May cause transient decrease in renal function and aggravate chronic kidney disease; caution in patients with severe anemia, in those with history of blood coagulation defects, or in those taking anticoagulants

Drug Name Heparin

Description

Augments activity of antithrombin III and prevents conversion of fibrinogen to fibrin. Does not actively lyse preformed clot, but it is able to inhibit further thrombogenesis after thrombolysis. Heparin should be administered to patients undergoing PCI. Prevents reaccumulation of clot after spontaneous fibrinolysis. Benefit as adjunctive therapy for streptokinase not clear.

Adult Dose60 U/kg (max 4000 U) IV bolus; followed by a 12 U/kg/h (max 1000 U/h) maintenance infusion


ContraindicationsDocumented hypersensitivity; subacute bacterial endocarditis, active bleeding; history of heparin-induced thrombocytopenia

InteractionsDigoxin, nicotine, tetracycline, and antihistamines may decrease effects; NSAIDs, aspirin, dextran, dipyridamole, and hydroxychloroquine may increase heparin toxicity

PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions Caution in severe hypotension and shock

Drug Name Enoxaparin (Lovenox)

Description Produced by partial chemical or enzymatic depolymerization of unfractionated heparin (UFH). LMWH differs from UFH by having a higher ratio of

antifactor Xa to antifactor IIa compared with UFH. Binds to antithrombin III, enhancing its therapeutic effect. The heparin-antithrombin III complex binds to and inactivates activated factor X (Xa) and factor II (thrombin). Does not actively lyse but is able to inhibit further thrombogenesis. Prevents reaccumulation of clot after spontaneous fibrinolysis.Advantages include intermittent dosing and decreased requirement for monitoring. Heparin anti–factor Xa levels may be obtained if needed to establish adequate dosing. No utility in checking aPTT (drug has wide therapeutic window and aPTT does not correlate with anticoagulant effect). Indicated for treatment of acute ST-segment elevation myocardial infarction (STEMI) managed medically or with subsequent percutaneous coronary intervention (PCI). Also indicated as prophylaxis of ischemic complications caused by unstable angina and non-Q-wave MI.

Adult Dose

Treatment regimens include aspirin (75-325 mg/d) if not contraindicatedNSTEMI1 mg/kg SC bidCrCl <30 mL/min: 1 mg/kg SC qdSTEMI<75 years: 30 mg IV single bolus plus 1 mg/kg SC, then 1 mg/kg SC q12h; not to exceed 100 mg/dose for first 2 SC doses<75 years and CrCl <30 mL/min: 30 mg IV single bolus plus 1 mg/kg SC, then 1 mg/kg SC qd; not to exceed 100 mg/dose for first 2 SC doses >75 years: 0.75 mg/kg SC q12h (no initial IV bolus administered), not to exceed 75 mg/dose for first 2 doses>75 years and CrCl <30 mL/min: 1 mg/kg SC qd (no initial IV bolus administered)With PCI: If last enoxaparin dose administered >8 h before balloon inflation, administer an additional IV bolus of 0.3 mg/kg With thrombolytic agent: Give dose specified for age and renal function between 15 min before and 30 min after the start of fibrinolytic therapy


ContraindicationsDocumented hypersensitivity; major bleeding; thrombocytopenia

Interactions

Platelet inhibitors or oral anticoagulants such as dipyridamole, salicylates, aspirin, NSAIDs, sulfinpyrazone, and ticlopidine may increase risk of bleeding

PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Decrease dose if CrCl <30 mL/min; if thromboembolic event occurs despite LMWH prophylaxis, discontinue drug and initiate alternate therapy; elevation of hepatic transaminase levels may occur but is reversible; heparin-associated thrombocytopenia may occur with fractionated low-molecular-weight heparins; 1 mg of protamine sulfate reverses effect of approximately 1 mg of enoxaparin if significant bleeding complications develop; cases of epidural/spinal hematomas have been reported in adults receiving spinal or epidural anesthesia (holding 2 doses prior to LP or surgery is recommended); obtain hemostasis at puncture site before sheath removal after PCI

Drug Category: Vasodilators

These agents oppose coronary artery spasm, which augments coronary blood flow and reduces cardiac work by decreasing preload and afterload. It is effective in the management of symptoms in AMI and has no apparent impact on mortality rate. Nitroglycerin can be administered sublingually by tablet or spray, topically, or intravenously. In the setting of AMI, topical administration is a less desirable route because of unpredictable absorption and onset of clinical effects.

Drug NameNitroglycerin (Minitran, Nitrogard, Nitrol, Nitrolingual, Nitrostat, Nitro-Dur)

DescriptionCauses relaxation of vascular smooth muscle by stimulating intracellular cyclic guanosine monophosphate production. Result is decrease in blood pressure.

Adult Dose

400 mcg SL tab or spray q5min, repeated up to 3 times; if symptoms persist, infuse IV at a rate of 5-10 mcg/min; titrate dose to 10% reduction in MAP or limiting side effects of hypotension (>30% reduction in MAP or systolic BP <90), or severe headache


Contraindications

Documented hypersensitivity; severe anemia; shock; postural hypotension; head trauma; closed-angle glaucoma; cerebral hemorrhage; known right ventricular infarct

Interactions

Aspirin may increase nitrate serum concentrations; marked symptomatic orthostatic hypotension may occur with coadministration of calcium channel blockers (dose adjustment of either agent may be necessary)


PrecautionsCaution in coronary artery disease and low systolic blood pressure

Drug Category: Beta-adrenergic blockers

These agents inhibit chronotropic, inotropic, and vasodilatory responses to beta-adrenergic stimulation and reduce blood pressure, which decreases myocardial oxygen demand. Short-term and long-term mortality rates are reduced in patients with AMI. Greatest benefit is achieved when given within 8 hours of symptom onset. Aim for a target heart rate of 60-90 beats per minute.

Drug Name Metoprolol (Lopressor)

Description

Selective beta1-adrenergic receptor blocker that decreases automaticity of contractions. During IV administration, carefully monitor blood pressure, heart rate, and ECG. Goal of treatment is to reduce heart rate to 60-90 bpm.

Adult Dose 5 mg IV q5min 3 times; titrate to heart rate and SBP


ContraindicationsDocumented hypersensitivity; uncompensated congestive heart failure; bradycardia; asthma; cardiogenic shock; AV conduction abnormalities

Interactions

Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels of metoprolol, possibly resulting in decreased pharmacologic effects; toxicity of metoprolol may increase with coadministration of sparfloxacin, phenothiazines, astemizole, calcium channel blockers, quinidine, flecainide, and contraceptives; metoprolol may increase toxicity of digoxin, flecainide, clonidine, epinephrine, nifedipine, prazosin, verapamil, and lidocaine


Precautions

Beta-adrenergic blockade may reduce signs and symptoms of acute hypoglycemia and may decrease clinical signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; monitor patient closely and withdraw the drug slowly; during IV administration, carefully monitor blood pressure, heart rate, and ECG

Drug Name Esmolol (Brevibloc)

Description Excellent drug for use in patients at risk for complications from beta-blockade, particularly those with reactive airway disease, mild-to-moderate LV dysfunction, and/or peripheral vascular disease. Short half-life of 8 min allows for titration to desired effect and quick discontinuation if

needed.

Adult Dose

Loading dose: 500 mcg/kg/min IV over 1 minOptional loading dose: 0.5 mg/kg slow IV infusionMaintenance dose: 0.1 mg/kg/min IV initially; titrate in increments of 0.05 mg/kg/min q10-15min to a total dose of 0.2 mg/kg/minAverage maintenance dose: 50 mcg/kg/min IV over 4 min


ContraindicationsDocumented hypersensitivity; uncompensated congestive heart failure; bradycardia; cardiogenic shock; AV conduction abnormalities; cocaine-related ischemia

Interactions

Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels of esmolol, possibly resulting in decreased pharmacologic effect; cardiotoxicity of esmolol may increase when administered concurrently with sparfloxacin, astemizole, calcium channel blockers, quinidine, flecainide, and contraceptives; toxicity of esmolol increases when administered concurrently with digoxin, flecainide, acetaminophen, clonidine, epinephrine, nifedipine, prazosin, haloperidol, phenothiazines, and catecholamine-depleting agents


Precautions

Beta-adrenergic blockers may mask signs and symptoms of acute hypoglycemia and clinical signs of hyperthyroidism; symptoms of hyperthyroidism, including thyroid storm may worsen when medication is abruptly withdrawn (withdraw drug slowly and monitor patient closely); caution in patients on other negative inotropes, such as verapamil

Drug Category: Thrombolytic agents

These agents prevent recurrent thrombus formation and rapid restoration of hemodynamic disturbances. In addition, they remove pathologic intraluminal thrombus or embolus not yet dissolved by the endogenous fibrinolytic system. When given within 12 h of symptom onset, they restore patency of occluded arteries, salvage myocardium, and reduce morbidity and mortality rates of AMI. Thrombolytic treatment should be started within 30 min of arrival (door-drug time). Maximum benefit occurs when administered within 1-3 h of symptom onset.

Drug Name Alteplase (Activase) or Reteplase (Retavase)

Description Alteplase: Fibrin-specific agent with a brief half-life of 5 min. Adjunctive therapy with IV heparin is necessary to

maintain patency of arteries recanalized by tPA, especially during the first 24-48 h. Heparin may be administered during tPA infusion.Reteplase: Recombinant plasminogen activator that forms plasmin after facilitating cleavage of endogenous plasminogen. In clinical trials, reteplase has been shown to be comparable to tPA in achieving TIMI 2 or 3 patency at 90 min.

Adult Dose

Alteplase: 15 mg IV bolus; 0.75 mg/kg IV over 30 min; not to exceed 50 mg; followed by 0.5 mg/kg over 60 min, up to 35 mg; not to exceed 100 mgReteplase: 10.8 U IV over 2 min; repeat in 30 min


Contraindications

Documented hypersensitivity; stroke within last 2 mo; intracranial or intraspinal surgery or trauma; intracranial hemorrhage on pretreatment evaluation; active internal bleeding; intracranial neoplasm; arteriovenous malformation or aneurysm; bleeding diathesis; severe uncontrolled hypertension; suspicion of subarachnoid hemorrhage

Interactions

Drugs that alter platelet function (aspirin, dipyridamole, abciximab) may increase risk of bleeding prior to, during, or after therapy; may give heparin with, and after, alteplase infusions to reduce risk of rethrombosis; either heparin or alteplase may cause bleeding complications


Precautions

Monitor for bleeding, especially at arterial puncture sites, with coadministration of vitamin K antagonists; control and monitor blood pressure frequently during and following therapy (when managing acute ischemic stroke); caution in cardiovascular arrhythmias, hypotension, and perfusion arrhythmiasDo not use >0.9 mg/kg alteplase to manage acute ischemic stroke; doses >0.9 mg/kg may cause ICH

Drug Name Tenecteplase (TNKase)

Description

Modified version of alteplase (tPA) made by substituting 3 amino acids of alteplase. Can be given as single bolus over 5-second infusion instead of 90 min with alteplase. Appears to cause less nonintracranial bleeding but has similar risk of intracranial bleeding and stroke as alteplase. Base the dose using patient weight. Initiate treatment as soon as possible after onset of AMI symptoms. Because tenecteplase contains no antibacterial preservatives, reconstitute immediately before use.

Adult Dose

Give IV bolus over 5 s using body weight; not to exceed 50 mg<60 kg: 30 mg (6 mL)60-70 kg: 35 mg (7 mL)70-80 kg: 40 mg (8 mL)80-90 kg: 45 mg (9 mL)>90 kg: 50 mg (10 mL)


Contraindications

Documented hypersensitivity; active internal bleeding; intracranial neoplasm; known bleeding diathesis; severe uncontrolled hypertension; arteriovenous malformation or aneurysm; history of stroke; intracranial or intraspinal surgery or trauma within 2 mo

InteractionsHeparin and vitamin K antagonists, acetylsalicylic acid, dipyridamole, and GP IIb/IIIa inhibitors may increase risk of bleeding if coadministered with tenecteplase therapy


Precautions

Caution if readministering to patients who have received prior plasminogen activator therapy (may develop immunity); coronary thrombolysis may result in arrhythmias associated with reperfusion but not different from those often observed in ordinary course of AMI (may be managed with standard antiarrhythmic measures); in elderly patients, weigh benefits of tenecteplase on mortality against risk of increased adverse events, including bleeding; cholesterol embolism is associated with all types of thrombolytic agents but true incidence is unknown

Drug Name Anistreplase (Eminase)

Description

Recently approved for use in AMI. Nonfibrin specific agent with a half-life of 90 min. Activates the conversion of plasminogen to plasmin, which is capable of degrading fibrin, fibrinogen, and other procoagulant proteins into soluble fragments. These effects result in thrombolysis. Has no survival benefit over streptokinase and higher rate of allergic and bleeding complications. Easier to administer than tPA, has a lower cost ($1500), and does not require heparinization.

Adult Dose 30 U IV over 2-5 min


Contraindications

Documented hypersensitivity; history of stroke; intracranial neoplasm; active internal bleeding; recent intracranial surgery; severe uncontrolled hypertension; arteriovenous malformation or aneurysm

InteractionsIncreases bleeding potential of heparin, warfarin, and aspirin


PrecautionsCaution in cardiovascular arrhythmias, hypotension, and perfusion arrhythmias

Drug Name Streptokinase (Kabikinase, Streptase)

Description

Nonfibrin specific agent with a half-life of 23 min. Need for adjunctive therapy with heparin is controversial. Acts with plasminogen to convert plasminogen to plasmin. Plasmin degrades fibrin clots as well as fibrinogen and other plasma proteins. An increase in fibrinolytic activity that degrades fibrinogen levels for 24-36 h takes place with intravenous infusion of streptokinase.

Adult Dose 1.5 million U in 50 mL D5W IV over 60 min


ContraindicationsDocumented hypersensitivity; active internal bleeding; intracranial neoplasm; aneurysm; diathesis; severe uncontrolled arterial hypertension

InteractionsAntifibrinolytic agents may decrease effects of streptokinase; heparin, warfarin, and aspirin may increase risk of bleeding


Precautions

Caution in severe hypertension, intramuscular administration of medications, and trauma or surgery in previous 10 d; measure hematocrit, platelet count, aPTT, TT, PT, or fibrinogen levels before therapy is implemented; either TT or aPTT should be less than twice the reference range control value following infusion of streptokinase and before (re)instituting heparin; PT, aPTT, TT or fibrinogen should be monitored 4 h after initiation of therapy

Drug Category: Platelet aggregation inhibitors

These agents inhibit platelet aggregation and reduce mortality.

Drug Name Clopidogrel (Plavix)

Description

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

Adult Dose 300 mg PO loading dose prior to PCI, then 75 mg PO qd


ContraindicationsDocumented hypersensitivity; active pathological bleeding, such as peptic ulcer; intracranial hemorrhage

InteractionsCoadministration with naproxen associated with increased occult GI blood loss; clopidogrel prolongs bleeding time; safety of coadministration with warfarin not established


Precautions

Caution in patients at increased risk of bleeding from trauma, surgery, or other pathological conditions; caution in patients with lesions with propensity to bleed (eg, ulcers)

Drug Name Eptifibatide (Integrilin)

Description

Antagonist of the platelet glycoprotein (GP) IIb/IIIa receptor, which reversibly prevents von Willebrand factor, fibrinogen, and other adhesion ligands from binding to the GP IIb/IIIa receptor. End effect is the inhibition of platelet aggregation. Effects persist over duration of maintenance infusion and are reversed when infusion ends.

Adult Dose

180 mcg/kg IV load; followed by 2 mcg/kg/min IV for 72 hPTCA: 135 mcg/kg IV bolus before procedure, followed by 0.5 mcg/kg/min IV for 20-24 h


Contraindications

Documented hypersensitivity; severe hypertension (SBP >200 mm Hg), active internal bleeding, history of intracranial hemorrhage, intracranial neoplasm, arteriovenous malformation or aneurysm, acute pericarditis or bleeding diathesis; trauma or stroke within previous 30 d; platelet count <100,000/mm3; history of thrombocytopenia following prior exposure to this product; serum creatinine level >2 mg/dL (for the 180-mcg/kg bolus and 2-mcg/kg/min infusion) or >4 mg/dL (for the 135-mcg/kg bolus and 0.5-mcg/kg/min infusion)

InteractionsCoadministration with heparin, warfarin, or aspirin may increase risk of bleeding; monitor closely when using other drugs that affect hemostasis


Precautions Caution in platelet count <150,000/mm3 and hemorrhagic retinopathy; caution with concurrent use of drugs that affect hemostasis, such as thrombolytics, ticlopidine,

NSAIDs, warfarin, dipyridamole, and clopidogrel; measure activated clotting time (ACT) and maintain aPTT between 50-70 s unless a PCI needs to be performed; maintain ACT between 300-350 s during a PCI; if platelets decrease to <100,000/mm3, perform additional platelet counts to exclude possibility of pseudothrombocytopenia; if thrombocytopenia is confirmed, discontinue GP IIb/IIIa inhibitors and heparin and appropriately monitor and treat the condition; monitor aPTT 6 h after start of heparin infusion and adjust to maintain aPTT higher than twice the baseline level

Drug Name Tirofiban (Aggrastat)

Description

Antagonist of the platelet glycoprotein (GP) IIb/IIIa receptor that reversibly prevents von Willebrand factor, fibrinogen, and other adhesion ligands from binding to the GP IIb/IIIa receptor, thereby inhibiting platelet aggregation. Effects persist over the duration of maintenance infusion and are reversed after stopping the infusion.

Adult Dose0.4 mcg/kg/min IV for 30 min; followed by 0.1 mcg/kg/min


Contraindications

Documented hypersensitivity; history of intracranial hemorrhage; severe hypertension (SBP >200 mm Hg), active internal bleeding, intracranial neoplasm, arteriovenous malformation or aneurysm, acute pericarditis and bleeding diathesis; trauma or stroke within previous 30 d; platelet count <100,000/mm3, history of thrombocytopenia following prior exposure to this product; serum creatinine level >2 mg/dL (for the 180-mcg/kg bolus and 2-mcg/kg/min infusion) or >4 mg/dL for the 135-mcg/kg bolus and the 0.5-mcg/kg/min infusion

InteractionsCoadministration with heparin, warfarin, and aspirin may increase risk of bleeding


Precautions Caution in platelet count <150,000/mm3 and hemorrhagic retinopathy; caution with concurrent use of drugs that affect hemostasis, such as thrombolytics, ticlopidine, NSAIDs, warfarin, dipyridamole, and clopidogrel; measure activated clotting time (ACT) and maintain aPTT between 50-70 s unless a PCI needs to be performed; maintain ACT between 300-350 s during a PCI; if platelets decrease to <100,000/mm3, perform additional platelet counts to exclude possibility of

pseudothrombocytopenia; if thrombocytopenia is confirmed, discontinue GP IIb/IIIa inhibitors and heparin, and appropriately monitor and treat condition; monitor aPTT 6 h after start of heparin infusion and adjust to maintain aPTT higher than twice baseline level

Drug Name Abciximab (ReoPro)

Description

Chimeric human-murine monoclonal antibody approved for use in elective/urgent/emergent PCI. Binds to receptor with high affinity and reduces platelet aggregation by 80% for as long as 48 h following infusion. Prevents acute cardiac ischemic complications in unstable angina unresponsive to conventional therapy.

Adult Dose 0.25 mg/kg IV bolus, followed by 10 mcg/min IV for 12 h


Contraindications

Documented hypersensitivity; bleeding diathesis; thrombocytopenia (<100,000 cells/mcL); recent trauma; intracranial tumor; severe uncontrolled hypertension; history of vasculitis; stroke within 2 y

InteractionsToxicity increases with coadministration of anticoagulants, antiplatelets, and thrombolytics


Precautions

Bleeding complications may occur in patients <75 kg body weight, >65 years, with history of GI disease, or who recently received thrombolytic therapy; severe thrombocytopenia may occur within first 24 h of use

Drug Category: Analgesics

These agents reduce pain, which decreases sympathetic stress. They may provide some preload reduction. Analgesics ensure patient comfort, promote pulmonary toilet, and have sedating properties, which are beneficial for patients who experience chest discomfort resulting from a myocardial infarction.

Drug Name Morphine sulfate (Duramorph, Astramorph, MS Contin)

Description

DOC for analgesia because of reliable and predictable effects, safety profile, and ease of reversibility with naloxone. Various IV doses are used; commonly titrated until desired effect obtained.

Adult Dose 1-3 mg IV; repeat and titrate to pain relief


ContraindicationsDocumented hypersensitivity; hypotension; potentially compromised airway where establishing rapid airway control would be difficult

Interactions Phenothiazines may antagonize analgesic effects of opiate

agonists; tricyclic antidepressants, MAOIs, and other CNS depressants may potentiate adverse effects of morphine


Precautions

Caution in severe hypotension, respiratory depression, nausea, emesis, constipation, urinary retention, atrial flutter, and other supraventricular tachycardias; has vagolytic action and may increase ventricular response rate

Drug Category: Angiotensin-converting enzyme (ACE) inhibitors

These agents prevent conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, causing lowered aldosterone secretion.

Drug Name Captopril (Capoten)

Description

Has short half-life, which makes it important drug for initiation of ACE inhibitor therapy. Can be started at low dose and titrated upward as needed and as patient tolerates.

Adult Dose 6.25 mg PO tid initially; may titrate to total 450 mg/d


Contraindications Documented hypersensitivity

Interactions

Patients receiving diuretic therapy, other vasodilator agents, agents causing renin release, agents increasing potassium, or agents affecting sympathetic activity should be monitored carefully


Precautions

Administer with caution in patients with renal insufficiency and in those with borderline low blood pressure; may worsen renal function, especially in patients with bilateral renal artery stenosis; administer cautiously in patients with aortic stenosis because afterload reduction may worsen coronary perfusion

FOLLOW-UP

Section 8 of 11

Further Inpatient Care

All patients with known or suspected MI should be admitted to an ICU. Patients should continue to receive beta-blockers, nitrates, and heparin, as indicated. ACE inhibitors have been shown to improve survival rates in patients who have experienced an MI. In

the acute setting, afterload reduction from ACE inhibitors may reduce the risk of CHF and sudden death. Lidocaine may be indicated for patients with ventricular ectopy that is complex or for patients with

hemodynamically significant, nonsustained, or sustained ventricular tachycardia. Recall that the routine use of lidocaine as prophylaxis for ventricular arrhythmias is contraindicated.

Transfer

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

Patients with new or worsening hemodynamically significant mitral regurgitant murmurs Patients with known or suspected critical aortic stenosis and either ongoing ischemia or

hemodynamic instability Patients who have received thrombolysis and fail to reperfuse Patients with significant LV dysfunction or cardiogenic shock

Deterrence/Prevention

Patients should avoid risk factors when possible and act upon treatable risk factors. Seeking medical attention or calling 911 with the first symptoms or signs of angina may initiate the

cascade of interventions that will ultimately prevent or limit damage to the myocardium. All patients should be educated as to these symptoms and signs and when to call 911.

Daily low-dose aspirin may be helpful, but the decision to prescribe aspirin as a preventative measure for MI must be made by the patient's physician(s) considering his or her overall condition and risk-benefit ratio.

Complications

Monitoring and treatment of arrhythmias and conduction disturbances are an important part of the treatment of a post-MI patient within the first 48 hours. Conduction disturbances are most commonly observed in inferior MI but are more ominous when they occur with anterior MI.

Tachyarrhythmiao Sinus tachycardia is a poor prognostic sign that is indicative of ventricular dysfunction or failure.o PVCs - Simple (ie, <10/h), no need to treato PVCs - Complex, NSVT/VT, lidocaine DOCo Accelerated idioventricular rhythm (AIVR) is the most common reperfusion arrhythmia, but it

usually is well tolerated and does not require treatment. Bradyarrhythmia

o Type I second-degree heart block (ie, Wenckebach) is associated with inferior wall MI. Treat

using temporary pacing or atropine only if it is hemodynamically significant.

o Type II second-degree heart block is associated with anterior wall MI and may require a permanent pacemaker. Bundle branch blocks (BBB) that are new or preexisting with new second-degree heart block may also mandate consideration for a permanent pacemaker.

Cardiogenic shocko In the setting of an MI, cardiogenic shock is associated with an 80% in-hospital mortality rate.o Patients should undergo thrombolysis or PCI, placement of an intra-aortic balloon pump, or

CABG. Valvular insufficiency

o This may occur acutely when ischemia or an infarct of the papillary muscle occurs resulting in

mitral regurgitation. It usually presents as flash pulmonary edema and hypotension. Papillary muscle rupture may require valve repair.

o Ischemia often responds to medical therapy and thrombolysis. Congestive heart failure can be due to systolic or diastolic dysfunction in MI. The severity of the heart

failure and systolic dysfunction depends on the extent of the infarct and the presence of any other complications, such as acute mitral regurgitation. Treatment may include nitrates, morphine, diuretics, and ACE inhibitors. Digoxin has no role in acute CHF due to ischemia.

Right ventricular infarct occurs in the setting of an inferior wall infarction. Because patients with an RV infarct are preload-dependent, they often are identified by profound hypotension with normal pulmonary auscultation, particularly after nitroglycerin therapy. They respond to volume loading. This can be diagnosed by ST-segment elevation in right-sided chest leads (ie, V4R, V5R).

Ventricular rupture occurs in the interventricular septum or the left ventricle free wall. Rupture represents a catastrophic event with mortality rates greater than 90%. Prompt recognition, stabilization, and surgical repair are crucial to any hope of survival. An echocardiogram usually defines the abnormality, and a right heart catheterization may show an oxygenation increase with septal rupture. It is more common in women, patients with hypertension, and those receiving NSAIDs or steroids.

Other complications include pericarditis, ventricular aneurysm, and mural thrombus.

Prognosis

MI may be associated with a mortality rate as high as 30%, with more than half of deaths occurring in the prehospital setting. Prognosis is highly variable and depends on a number of factors related to the timing and nature of intervention, success of the intervention (ie, infarct size), and post-MI management.

Better prognosis is associated with factors including the following:o Successful early reperfusion o Preserved LV function o Short-term and long-term treatment with beta-blockers, aspirin, and ACE inhibitors

Poorer prognosis is associated with the following:o Delayed or unsuccessful reperfusion o LV function is the strongest predictor of outcome in the post-MI patient.

Ventricular dysrhythmiaso Recent experience with amiodarone suggests that it may improve long-term mortality in

survivors of MI with ectopy and ventricular tachycardia.

Patient Education

For excellent patient education resources, see eMedicine's Cholesterol Center. Also, visit eMedicine's patient education articles Chest Pain, Coronary Heart Disease, and Heart Attack.

All patients must be educated on the need to call 911 for symptoms and signs of ACS or MI. All patients must be aggressively encouraged to quit smoking.

MISCELLANEOUS

Section 9 of 11

Medical/Legal Pitfalls

Failure to diagnose MI can result in costly litigation. In most studies, this diagnosis accounts for the largest sum of dollars paid out. The often-grim outcome adds a major emotional cost to the physician.

Attribution of epigastric or chest symptoms from myocardial ischemia to a GI source may lead to litigation. Often, this is done 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). Remember that even myocardial ischemia can worsen with recumbency (eg, angina decubitus) because of an increase in venous return and a temporary greater workload.

Attribution of the discomfort of myocardial ischemia to a musculoskeletal etiology may lead to litigation. Tenderness of the chest wall is reported in as many as 5% of patients who prove to have an 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.

Aortic dissection can also be a pitfall if a retrograde dissection is present. The dissection may extend to the pericardial sac and produce cardiac tamponade or disrupt the origin of a coronary artery producing STEMI as a complication of dissection. Thrombolytics administration to such a patient could produce disastrous results.

Younger patients are overly represented in cases of missed MI. Most likely, this is because of the inherent bias that this is a disease of those who are late middle-aged and older. Approach each patient with chest symptoms as an individual who could have the disease.

ECG misinterpretationo Unfortunately, in a series of missed MI, the failure to recognize ischemic changes is frequent.

The inferior leads, in particular, must be scrutinized carefully for any evidence of ST-segment elevation by using a straight edge across the T-P segments.

o Another common error is to recognize ischemic changes and then discharge the patient without definitively proving that the changes were pre-existent. Nonischemic causes of ST-segment elevation include LVH, pericarditis, ventricular-paced rhythms, hypothermia, hyperkalemia, and LV aneurysm. Nonischemic causes may lead to over treatment.

Failure to diagnose an MI in the setting of a left bundle-branch block may lead to litigation. Criteria for the diagnosis are as follows:

1. ST-segment elevation greater than 1 mm and concordant with QRS complex

2. ST-segment depression greater than 1 mm in lead V1, V2, or V3

3. ST-segment elevation greater than 5 mm and discordant with QRS complex

http://www.emedicinehealth.com/articles/11029-1.asp



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These criteria have been assigned a score from 1-5. A score of 3 is necessary for specificity for MI of 90%. The first criterion is scored a 5, the second is scored a 3, and the third is scored a 2.

Delays or failure to administer thrombolytics or to initiate PCI may lead to litigation.

o This is usually because of delays in ECG performance, interpretation, and decision-making, and it is also affected by the availability of thrombolytics in ED.

o Excluding patients based on age alone will deny some the significant benefit of thrombolysis.

NEW DEFINITION OF “MI”

New Definition of "MI" Poised for World Domination CME

News Author: Steve StilesCME Author: Charles Vega, MD Disclosures

Release Date: October 23, 2007; Valid for credit through October 23, 2008 Credits Available

Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™ for physicians;Family Physicians - up to 0.25 AAFP Prescribed credit(s) for physicians

from Heart wire — a professional news service of WebMD

October 23, 2007 — A new consensus report [1] sponsored jointly by four cardiology societies refines and expands on the definition of "myocardial infarction" last updated seven years ago [2] and — in a bold move — recognizes five separate myocardial infarction (MI) categories based on differences in pathophysiology and whether percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery is involved.

The new definition's components reflect knowledge and skills gained since the last time, much of which has been commonly used in clinical practice and research, though inconsistently and without a formal mandate.

"What's not different is that troponin together with clinical information from the patient history and the electrocardiogram are still the gold standard," Dr Joseph S Alpert (University of Arizona, Tucson) told heartwire.

The document notes that troponin is the "preferred" biomarker but that others, such as the MB fraction of creatinine kinase (CK-MB), can suffice when troponin testing is unavailable. Other innovations include criteria for MI as the cause of sudden death and unprecedented weight given to findings from echocardiography, perfusion scans, and other imaging techniques.

One goal for the consensus document is to nail down specific criteria for making an MI diagnosis that will be modern, useful, and relevant most everywhere.

"What we're trying to do is standardize the definition so that all clinical trials and people at hospitals around the world will on the same page," said Alpert, a cochair of the task force behind the "expert consensus document"

http://www.theheart.org/

http://www.medscape.com/viewarticle/564652_author

jointly sponsored by the American College of Cardiology (ACC), American Heart Association (AHA), European Society of Cardiology (ESC), and the World Heart Federation (WHF).

The report was published October 19, 2007 on the ACC, AHA, and ESC web sites, appears in the second October, 2007 edition of the European Heart Journal, and is scheduled for the November 27, 2007 issues of the Journal of the American College of Cardiology and Circulation.

Usually key to the diagnosis, with some notable exceptions, is an elevation in levels of troponin or other biomarkers exceeding the 99th percentile of the upper reference limit (URL), combined with the familiar clinical syndrome, electrocardiogram (ECG) signs, or imaging evidence of new myocardial ischemia.

The new criteria's effects may take some getting used to. Even in the absence of ECG changes, "if you have a syndrome consistent with myocardial infarction or acute coronary syndrome, with [such] a troponin elevation, then those two alone are sufficient to make the diagnosis," according to Dr Keith Fox (University of Edinburgh, UK). With troponin's specificity for myocardial necrosis at the specified concentration threshold, he observed, a great many more patients who would be missed by "previously conventional markers like CK and CK-MB" will be classified as having an MI.

"It will increase by about a quarter the prevalence of myocardial infarction," he said.

Fox made the remarks during a Cardiology Panel discussion sponsored by theheart.org [3] that was recorded in September after the new MI definition was described at the European Society of Cardiology 2007 Scientific Meeting.

The new definition also formally recognizes myocardial necrosis associated with PCI or CABG as an MI as long as a biomarker threshold is met, and allows the diagnosis in the absence of biomarker elevations in the setting of sudden cardiac death as long as there is evidence of myocardial ischemia.

With the MI definition's increased complexity comes to a classification system to sort out the variations, starting with the syndrome's classic pathophysiology.

New clinical classification of MI

Classification Description

1 Spontaneous MI related to ischemia due to a primary coronary event, such as plaque erosion and/or rupture, fissuring, or dissection

2 MI secondary to ischemia due to an imbalance of O2 supply and demand, as from coronary spasm or embolism, anemia, arrhythmias, hypertension, or hypotension

3 Sudden unexpected cardiac death, including cardiac arrest, often with symptoms suggesting ischemia with new ST-segment elevation; new left bundle branch block; or pathologic or angiographic evidence of fresh coronary thrombus — in the absence of reliable biomarker findings

4a MI associated with PCI

4b MI associated with documented in-stent thrombosis

5 MI associated with CABG surgery

The system goes far beyond the long-outmoded distinctions of transmural vs nontransmural or Q-wave vs non-Q-wave MI, and even the contemporary terms ST-elevation and non-ST-elevation MI (STEMI and non-STEMI). "The distinction between STEMI and non-STEMI is becoming clinically less interesting," Alpert said. "We hope, and we recommend, that in the future in clinical trials and routinely in the hospital, people will begin to characterize infarction by the different categories."

The classifications and updated diagnostic criteria could ultimately improve patient care and outcomes, he predicted. With a broader range of patients classified as having an MI, many who might have been labeled with "unstable angina" will get more aggressive management, said Alpert, "which should result in a decrease in mortality."

When speaking to heartwire, Alpert gave primary credit for the classification system and its inclusion in the document to task-force cochair Dr Harvey E White (Auckland City Hospital, New Zealand).

A detailed listing of disclosure information for members of the "Task Force for the Redefinition of Myocardial Infarction" appears at the end of the document, which also notes contributions of "unrestricted educational grants" from several companies, "none of whom were involved in the development of this publication and in no way influenced its contents." They are AstraZeneca, Beckman-Coulter, Dade Behring, GlaxoSmithKline, Roche Diagnostics, Sanofi-Aventis, and Servier.

Sources

1. Thygesen K, Alpert JS, White HD, et al. Universal definition of myocardial infarction. Circulation, published online before print October 19, 2007. DOI: 10.1161/CIRCULATIONAHA.107.187397

2. Alpert JS, Thygesen K, Antman E, et al. Myocardial infarction redefined — a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol 2000;36:959-969. PMID: 10987628

3. Are we ready for a troponin-based definition of MI?. theheart.org. [Editorial series > Cardiology panels]; October 17, 2007. Accessed at http://www.theheart.org/article/819427.do on October 19, 2007.

The complete contents of Heart wire , a professional news service of WebMD, can be found at www.theheart.org, a Web site for cardiovascular

healthcare professionals.

Clinical Context

Cardiovascular disease accounts for approximately one third of all deaths worldwide, and the vast majority of these deaths occur in developing countries. New tests and technologies have generally improved the sensitivity of detecting cardiac ischemia, but these same modalities have led to greater confusion regarding the definition of MI. The current recommendations from the ESC, the ACC, the AHA, and the WHF update the definition of MI, and different parameters to define MI are described in the "Study Highlights" section.

Study Highlights

Recommendations include:o Rise of cardiac biomarkers above the 99th percentile of upper reference limit with evidence of at

least 1 of the following signs of ischemia: Symptoms of ischemia: The discomfort of cardiac ischemia usually lasts at least 20

minutes and is diffused as opposed to localized. ECG changes indicative of ischemia in the absence of left-bundle branch block and left

ventricular hypertrophy. The earliest ECG manifestations of myocardial ischemia are



http://www.theheart.org/article/819427.do

typical T-waves and ST segment changes. ST elevation is defined by elevation at the J-point in 2 contiguous leads with the cutoff points of at least 0.2 mV in men or at least 0.15 mV in women in leads V2-V3 and/or at least 0.1 mV in other leads. ST depression is defined by at least 0.05 mV in 2 contiguous leads. T-wave inversion is significant when is at least 0.1 mV in 2 contiguous leads with a prominent R wave or R/S ratio greater than 1.

Development of pathologic Q waves on ECG. New left-bundle branch block. Imaging evidence of new loss of viable myocardium or new regional wall motion

abnormality. Biomarkers generally take precedence over cardiac imaging in diagnosing MI, but a normal echocardiogram or resting ECG-gated scintigram has a high negative-predictive value for excluding acute MI.

Sudden, unexpected cardiac death, often with symptoms of new cardiac ischemia, ECG changes consistent with ischemia, or evidence of fresh coronary thrombus on angiography or autopsy.

For patients undergoing PCI in the setting of normal troponin values, elevations of cardiac biomarkers above the 99th percentile of the upper limit of normal are indicative of periprocedural myocardial necrosis. Increases of biomarkers by more than 3 times above the 99th percentile of the upper reference limit are indicative of MI related to PCI.

Among patients undergoing CABG, elevations of cardiac biomarkers above the 99th percentile of the upper limit of normal are also indicative of periprocedural myocardial necrosis. Increases of biomarkers by more than 5 times above the 99th percentile of the upper reference limit plus any 1 of the following are indicative of MI related to CABG:

o New pathologic Q waves.o New left bundle-branch block.o New angiographic evidence of coronary artery occlusion.o New loss of viable myocardium on cardiac imaging.

Pathologic findings of an acute MI. Prior MI may be defined by any of the following criteria:

o Development of new pathologic Q waves with or without symptoms.o Imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract,

in the absence of a non-ischemic cause.o Pathologic findings of a healed or healing MI.

Pearls for Practice

ECG changes associated with cardiac ischemia are ST elevation in at least 2 contiguous leads of at least 0.2 mV in men or at least 0.15 mV in women in leads V2-V3 and/or at least 0.1 mV in other leads. ST depression is defined by at least 0.05 mV in 2 contiguous leads. T-wave inversion is significant when is at least 0.1 mV in 2 contiguous leads with a prominent R wave or R/S ratio greater than 1.

The current review suggests that cardiac biomarkers are a primary means of diagnosing MI, but patient symptoms, ECG findings, and cardiac imaging can also play a role in the diagnosis.

What should be your strategy when you suspect that the patient may have Myocardial infarction in the Emergency room ?

Oxygen by nasal cannula Sublingual Nitroglycerine Adequate analgesia Aspirin 160-325 mgm

12 lead EKG Draw baseline Cardiac Enzyme markers Limit activities Use of Heparin, Beta blocker, ACE inhibitor Admit patient to ICU Abort the infarct

o Decide on early reperfusion strategy with Cardiology consultation and do it.

The goals of therapeutic strategy for MI:

To alter supply/demand of oxygen to Myocardium To prevent further progression of Thrombus/clot To re-establish perfusion To treat complications

SOURCES:

1: http://www.emedicine.com/emerg/topic327.htm

2 : http://www.medscape.com/viewarticle/564652

http://www.medscape.com/viewarticle/564652


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