CHAPTER II DISCUSSION A.

Definition Acute myocardial infarction (AMI or MI), commonly known as a heart attack, is a disease state that occurs when the blood supply to a part of the heart is interrupted. The resulting ischemia or oxygen shortage causes damage and potential death of heart tissue. It is a medical emergency, and the leading cause of death for both men and women all o er the world. Important risk factors are a pre ious history of ascular disease such as atherosclerotic coronary heart disease and!or angina, a pre ious heart attack or stroke, any pre ious episodes of abnormal heart rhythms or syncope, older age"especially men o er #$ and women o er %$, smoking, excessi e alcohol consumption, the abuse of certain illicit drugs, high triglyceride le els, high &'& ((&ow)density lipoprotein() and low *'& ((*igh density lipoprotein(), diabetes, high blood pressure, obesity, and chronically high le els of stress in certain persons. 'iagram of a myocardial infarction (/) of the tip of the anterior wall of the heart (an apical infarct) after occlusion (0) of a branch of the left coronary artery (&+A, right coronary artery 1 2+A). The term myocardial infarction is deri ed from myocardium (the heart muscle) and infarction (tissue death due to oxygen star ation). The phrase (heart attack( is sometimes used incorrectly to describe sudden cardiac death, which may or may not be the result of acute myocardial infarction. +lassical symptoms of acute myocardial infarction include chest pain, shortness of breath, nausea, omiting, palpitations, sweating, and anxiety or a feeling of impending doom. ,atients fre-uently feel suddenly ill. .omen often experience different symptoms than men. The most common symptoms of MI in women include shortness of breath, weakness, and fatigue. Approximately one third of all myocardial infarctions are silent, without chest pain or other symptoms.

Immediate treatment for suspected acute myocardial infarction includes oxygen, aspirin, glyceryl trinitrate and pain relief. The patient will recei e a number of diagnostic tests, such as an electrocardiogram (3+4, 354), a chest 6)ray and blood tests to detect ele ated creatine kinase or troponin le els (these are chemical markers released by damaged tissues, especially the myocardium). 7urther treatment may include either medications to break down blood clots that block the blood flow to the heart, or mechanically restoring the flow by dilatation or bypass surgery of the blocked coronary artery. +oronary care unit admission allows rapid and safe treatment of complications such as abnormal heart rhythms. B.Epidemiology Myocardial infarction is a common presentation of ischemic heart disease. The .*8 estimated that in /$$/, 0/.9: of deaths worldwide were from ischemic heart disease. Ischemic heart disease is the leading cause of death in de eloped countries, but third to AI'; and lower respiratory infections in de eloping countries. In the <nited ;tates, diseases of the heart are the leading cause of death, causing a higher mortality than cancer (malignant neoplasms). +oronary heart disease is responsible for 0 in % deaths in the <.;... ;ome =,/$$,$$$ men and 9,$$$,$$$ women are li ing with some form of coronary heart disease. 0,/$$,$$$ people suffer a (new or recurrent) coronary attack e ery year, and about #$: of them die as a result of the attack. This means that roughly e ery 9% seconds, an American dies of a coronary e ent. C. Risk fa to!s 2isk factors for atherosclerosis are generally risk factors for myocardial infarction>

8lder age Male gender +igarette smoking *ypercholesterolemia (more accurately hyperlipoproteinemia, especially high low density lipoprotein and low high density lipoprotein) 'iabetes (with or without insulin resistance) *igh blood pressure

8besity (defined by a body mass index of more than ?$ kg!m/, or alternati ely by waist circumference or waist)hip ratio). Many of these risk factors are modifiable@ so many heart attacks can be pre ented by maintaining

a healthier lifestyle. ,hysical acti ity, for example, is associated with a lower risk profile. Aon) modifiable risk factors include age, gender, and family history of an early heart attack (before the age of 9$), which is thought of as reflecting a genetic predisposition. ;ocioeconomic factors such as a shorter education and lower income (particularly in women), and li ing with a partner may also contribute to the risk of MI. To understand epidemiological study results, itBs important to note that many factors associated with MI mediate their risk ia other factors. 7or example, the effect of education is partially based on its effect on income and marital status. .omen who use combined oral contracepti e pills ha e a modestly increased risk of myocardial infarction, especially in the presence of other risk factors, such as smoking. Inflammation is known to be an important step in the process of atherosclerotic pla-ue formation. +)reacti e protein (+2,) is a sensiti e but non)specific marker for inflammation. 3le ated +2, blood le els, especially measured with high sensiti ity assays, can predict the risk of MI, as well as stroke and de elopment of diabetes. Moreo er, some drugs for MI might also reduce +2, le els. The use of high sensiti ity +2, assays as a means of screening the general population is ad ised against, but it may be used optionally at the physicianBs discretion, in patients who already present with other risk factors or known coronary artery disease. .hether +2, plays a direct role in atherosclerosis remains uncertain. Inflammation in periodontal disease may be linked coronary heart disease, and since periodontitis is ery common, this could ha e great conse-uences for public health ;erological studies measuring antibody le els against typical periodontitis)causing bacteria found that such antibodies were more present in subCects with coronary heart disease ,eriodontitis tends to increase blood le els of +2,, fibrinogen and cytokines@ thus, periodontitis may mediate its effect on MI risk ia other risk factors. ,reclinical research suggests that periodontal bacteria can promote aggregation of platelets and promote the formation of foam cells. A role for specific periodontal bacteria has been suggested but remains to be established.

Daldness, hair greying, a diagonal crease and possibly other skin features are independent risk factors for MI. Their role remains contro ersial@ a common denominator of these signs and the risk of MI are supposed, possibly genetic.

D. Pat"op"ysiology

A myocardial infarction occurs when an atherosclerotic pla-ue slowly builds up in the inner lining of a coronary artery and then suddenly ruptures, totally occluding the artery and pre enting blood flow downstream. Acute myocardial infarction is a type of acute coronary syndrome, which is most fre-uently (but not always) a manifestation of coronary artery disease. The most common triggering e ent is the disruption of an atherosclerotic pla-ue in an epicardial coronary artery, which leads to a clotting cascade, sometimes resulting in total occlusion of the artery. Atherosclerosis is the gradual buildup of cholesterol and fibrous tissue in pla-ues in the wall of arteries (in this case, the coronary arteries), typically o er decades. Dlood stream column irregularities isible on angiographies reflect artery lumen narrowing as a result of decades of ad ancing atherosclerosis. ,la-ues can become unstable, rupture, and additionally promote a thrombus (blood clot) that occludes the artery@ this can occur in minutes.

.hen a se ere enough pla-ue rupture occurs in the coronary asculature, it leads to myocardial infarction (necrosis of downstream myocardium). If impaired blood flow to the heart lasts long enough, it triggers a process called the ischemic cascade@ the heart cells die (chiefly through necrosis) and do not grow back. A collagen scar forms in its place. 2ecent studies indicate that another form a cell death called apoptosis also plays a role in the process of tissue damage subse-uent to myocardial infarction. As a result, the patientBs heart can be permanently damaged. This scar tissue also puts the patient at risk for potentially life threatening arrhythmias. InCured heart tissue conducts electrical impulses more slowly than normal heart tissue. The difference in conduction elocity between inCured and uninCured tissue can trigger re)entry or a feedback loop that is belie ed to be the cause of many lethal arrhythmias. The most serious of these arrhythmias is entricular fibrillation (E)7ib!E7), an extremely fast and chaotic heart rhythm that is the leading cause of sudden cardiac death. Another life threatening arrhythmia is entricular tachycardia (E)Tach!ET), which may or may not cause sudden cardiac death. *owe er, entricular tachycardia usually results in rapid heart rates that pre ent the heart from pumping blood effecti ely. +ardiac output and blood pressure may fall to dangerous le els, which is particularly bad for the patient experiencing acute myocardial infarction. The cardiac defibrillator is a de ice that was specifically designed to terminate these potentially fatal arrhythmias. The de ice works by deli ering an electrical shock to the patient in order to depolariFe a critical mass of the heart muscle, in effect (rebooting( the heart. This therapy is time dependent, and the odds of successful defibrillation decline rapidly after the onset of cardiopulmonary arrest. E. T!igge!s *eart attack rates are higher in association with intense exertion, be it psychological stress or physical exertion, especially if the exertion is more intense than the indi idual usually performs Guantitati ely, the period of intense exercise and subse-uent reco ery is associated with about a 9)fold higher myocardial infarction rate (compared with other more relaxed time frames) for people who are physically ery fit 7or those in poor physical condition, the rate differential is o er ?%)fold higher. 8ne obser ed mechanism for this phenomenon is the increased arterial pulse pressure stretching and

relaxation of arteries with each heart beat which, as has been obser ed with intra ascular ultrasound, increases mechanical (shear stress( on atheromas and the likelihood of pla-ue rupture. Acute se ere infection, such as pneumonia, can trigger myocardial infarction. A more contro ersial link is that between +hlamydophila pneumoniae infection and atherosclerosis. .hile this intracellular organism has been demonstrated in atherosclerotic pla-ues, e idence is inconclusi e as to whether it can be considered a causati e factor. Treatment with antibiotics in patients with pro en atherosclerosis has not demonstrated a decreased risk of heart attacks or other coronary ascular diseases.

#. Classifi ation

+lassification of acute coronary syndromes Acute myocardial infarction is a type of acute coronary syndrome, which is most fre-uently (but not always) a manifestation of coronary artery disease. The acute coronary syndromes include ;T segment ele ation myocardial infarction (;T3MI), non);T segment ele ation myocardial infarction (A;T3MI), and unstable angina (<A).

'epending on the location of the obstruction in the coronary circulation, different Fones of the heart can become inCured. <sing the anatomical terms of location, one can describe anterior, inferior, lateral, apical and septal infarctions (and combinations, such as anteroinferior, anterolateral, and so on). 7or example, an occlusion of the left anterior descending coronary artery will result in an anterior wall myocardial infarct. Another distinction is whether a MI is subendocardial, affecting only the inner third to one half of the heart muscle, or transmural, damaging (almost) the entire wall of the heart. The inner part of the heart muscle is more ulnerable to oxygen shortage, because the coronary arteries run inward from the epicardium to the endocardium, and because the blood flow through the heart muscle is hindered by the heart contraction. The phrases transmural and subendocardial infarction used to be considered synonymous with G)wa e and non)G)wa e myocardial infarction respecti ely, based on the presence or absence of G wa es on the 3+4. It has since been shown that there is no clear correlation between the presence of G wa es with a transmural infarction and the absence of G wa es with a subendocardial infarction, but G wa es are associated with larger infarctions, while the lack of G wa es is associated with smaller infarctions. The presence or absence of G)wa es also has clinical importance, with impro ed outcomes associated with a lack of G wa es. $. Symptoms

2ough diagram of pain Fones in myocardial infarction (dark red 1 most typical area, light red 1 other possible areas, iew of the chest). The onset of symptoms in myocardial infarction (MI) is usually gradual, o er se eral minutes, and rarely instantaneous. +hest pain is the most common symptom of acute myocardial infarction and is often described as a sensation of tightness, pressure, or s-ueeFing. +hest pain due to ischemia (a lack

of blood and hence oxygen supply) of the heart muscle is termed angina pectoris. ,ain radiates most often to the left arm, but may also radiate to the lower Caw, neck, right arm, back, and epigastrium, where it may mimic heartburn. Any group of symptoms compatible with a sudden interruption of the blood flow to the heart is called an acute coronary syndrome. 8ther conditions such as aortic dissection or pulmonary embolism may present with chest pain and must be considered in the differential diagnosis. ;hortness of breath (dyspnea) occurs when the damage to the heart limits the output of the left entricle, causing left entricular failure and conse-uent pulmonary edema. 8ther symptoms include diaphoresis (an excessi e form of sweating), weakness, light)headedness, nausea, omiting, and palpitations. &oss of consciousness and e en sudden death can occur in myocardial infarctions. .omen often experience markedly different symptoms than men. The most common symptoms of MI in women include dyspnea, weakness, and fatigue. 7atigue, sleep disturbances, and dyspnea ha e been reported as fre-uently occurring symptoms which may manifest as long as one month before the actual clinically manifested ischemic e ent. In women, chest pain may be less predicti e of coronary ischemia than in men. Approximately half of all MI patients ha e experienced warning symptoms such as chest pain prior to the infarction. Approximately one third of all myocardial infarctions are silent, without chest pain or other symptoms. These cases can be disco ered later on electrocardiograms or at autopsy without a prior history of related complaints. A silent course is more common in the elderly, in patients with diabetes mellitus and after heart transplantation, probably because the donor heart is not connected to ner es of the host. In diabetics, differences in pain threshold, autonomic neuropathy, and psychological factors ha e been cited as possible explanations for the lack of symptoms. H. Diagnosis The diagnosis of myocardial infarction is made by integrating the history of the presenting illness and physical examination with electrocardiogram findings and cardiac markers (blood tests for heart muscle cell damage). A coronary angiogram allows isualiFing narrowings or obstructions on the heart essels, and therapeutic measures can follow immediately. At autopsy, a pathologist can diagnose a myocardial infarction based on anatomopathological findings.

A chest radiograph and routine blood tests may indicate complications or precipitating causes and are often performed on admittance to an emergency department. Aew regional wall motion abnormalities on an echocardiogram are also suggesti e of a myocardial infarction and are sometimes performed in e-ui ocal cases. Technetium and thallium can be used in nuclear medicine to isualiFe areas of reduced blood flow and tissue iability, respecti ely. Technetium is used in a M<4A scan. Diagnosti !ite!ia> .*8 criteria ha e classically been used to diagnose MI@ a patient is diagnosed with myocardial infarction if two (probable) or three (definite) of the following criteria are satisfied> 0. +linical history of ischemic type chest pain lasting for more than /$ minutes /. +hanges in serial 3+4 tracings ?. 2ise and fall of serum cardiac enFymes (biomarkers) such as creatine kinase, troponin I, and lactate dehydrogenase isoFymes specific for the heart. The .*8 criteria were refined in /$$$ to gi e more prominence to cardiac biomarkers. According to the new guidelines, a cardiac troponin rise accompanied by either typical symptoms, pathological G wa es, ;T ele ation or depression or coronary inter ention are diagnostic of MI.

a. P"ysi al e%amination> The general appearance of patients may ary according to the experienced symptoms@ the patient may be comfortable, or restless and in se ere distress with an increased respiratory rate. A cool and pale skin is common and points to asoconstriction. ;ome patients ha e low)grade fe er (?HI?J K+). Dlood pressure may be ele ated or decreased, and the pulse can be become irregular. If heart failure ensues, ele ated Cugular enous pressure and hepatoCugular reflux, or swelling of the legs due to peripheral edema may be found on inspection. 2arely, a cardiac bulge with a pace different from the pulse rhythm can be felt on pericardial examination. Earious abnormalities can be found on auscultation, such as a third and fourth heart sound, systolic murmurs, paradoxical splitting of the second heart sound, a pericardial friction rub and rales o er the lung.

0/)lead electrocardiogram (3+4) showing acute inferior ;T segment ele ation MI (;T3MI). Aote the ;T segment ele ation in leads II, III, and aE7 along with reciprocal ;T segment depression in leads I and aE&. &. Ele t!o a!diog!am' The primary purpose of the electrocardiogram is to detect ischemia or acute coronary inCury in broad, symptomatic emergency department populations. *owe er, the standard 0/ lead 3+4 has se eral limitations. An 3+4 represents a brief sample in time. Decause unstable ischemic syndromes ha e rapidly changing supply ersus demand characteristics, a single 3+4 may not accurately represent the entire picture. It is therefore desirable to obtain serial 0/ lead 3+4s, particularly if the first 3+4 is obtained during a pain)free episode. Alternati ely, many emergency departments and chest pain centers use computers capable of continuous ;T segment monitoring. It should also be appreciated that the standard 0/ lead 3+4 does not directly examine the right entricle, and does a relati ely poor Cob of examining the posterior basal and lateral walls of the left entricle. In particular, acute myocardial infarction in the distribution of the circumflex artery is likely to produce a non diagnostic 3+4. The use of non)standard 3+4 leads like right)sided lead E#2 and posterior leads E=, EH, and EJ may impro e sensiti ity for right entricular and posterior myocardial infarction. In spite of these limitations, the 0/ lead 3+4 stands at the center of risk stratification for the patient with suspected acute myocardial infarction. Mistakes in interpretation are relati ely common, and the failure to identify high risk features has a negati e effect on the -uality of patient care. The 0/ lead 3+4 is used to classify patients into one of three groups>

0. Those with ;T segment ele ation or new bundle branch block (suspicious for acute inCury and a possible candidate for acute reperfusion therapy with Thrombolytic or primary ,+I), /. Those with ;T segment depression or T wa e in ersion (suspicious for ischemia), and ?. Those with a so)called non)diagnostic or normal 3+4. A normal 3+4 does not rule out acute myocardial infarction. ;ometimes the earliest presentation of acute myocardial infarction is the hyper acute T wa e, which is treated the same as ;T segment ele ation. In practice this is rarely seen, because it only exists for /)?$ minutes after the onset of infarction. *yper acute T wa es need to be distinguished from the peaked T wa es associated with hyperkalemia. The current guidelines for the 3+4 diagnosis of acute myocardial infarction re-uire at least 0 mm ($.0 mE) of ;T segment ele ation in / or more anatomically contiguous leads. This criterion is problematic, howe er, as acute myocardial infarction is not the most common cause of ;T segment ele ation in chest pain patients. In addition, o er J$: of healthy men ha e at least 0 mm ($.0 mE) of ;T segment ele ation in at least one precordial lead. The clinician must therefore be well ersed in recogniFing the so)called 3+4 mimics of acute myocardial infarction, which include left entricular hypertrophy, left bundle branch block, paced rhythm, benign early repolariFation, ,ericarditis, hyperkalemia, and entricular aneurysm. &eft bundle branch block and pacing can interfere with the electrocardiography diagnosis of acute myocardial infarction. The 4<;T8 in estigators ;garbossa et al. de eloped a set of criteria for identifying acute myocardial infarction in the presence of left bundle branch block and paced rhythm. They include concordant ;T segment ele ation L 0 mm ($.0 mE), discordant ;T segment ele ation L % mm ($.% mE), and concordant ;T segment depression in the left precordial leads. The presence of reciprocal changes on the 0/ lead 3+4 may help distinguish true acute myocardial infarction from the mimics of acute myocardial infarction. The contour of the ;T segment may also be helpful, with a straight or upwardly con ex (non)conca e) ;T segment fa oring the diagnosis of acute myocardial infarction. The presence of ;T segment ele ation distinguishes between>

;T3MI ((;T)3le ation Myocardial Infarction() A;T3MI ((Aon);T)3le ation Myocardial Infarction() )) diagnosed when cardiac enFymes are ele ated.

The leads with ;T segment ele ation help the clinician identify what area of the heart is infarcting. It also enables the clinician to predict the culprit artery> &eads ;howing .all Affected ;T ;egment 3le ation ;eptal E0, E/ &eads ;howing 2eciprocal ;T ;egment 'epression Aone &eft Anterior 'escending (&A') &eft Anterior 'escending (&A') &eft Anterior 'escending (&A') &eft Anterior 'escending II, III, aE7 (&A'), +ircumflex (&+6), or 8btuse Marginal &eft main coronary artery (&+A) 2ight +oronary Artery (2+A) or +ircumflex (&+6) +ircumflex (&+6) or 8btuse Marginal ,osterior 'escending (,'A) E0,E/,E?, E# (branch of the 2+A or +ircumflex (&+6)) II, III, aE7, E0, E#2 I, aE& 2ight +oronary Artery (2+A) ;uspected +ulprit Artery

Anterior

E?, E#

Aone

Anteroseptal

E0, E/, E?, E#

Aone

Anterolateral

E?, E#, E%, E9, I, aE&

3xtensi e anterior (;ometimes called Anteroseptal with &ateral extension) Inferior

E0,E/,E?, E#, E%, E9, I, aE&

II, III, aE7

II, III, aE7

I, aE&

&ateral ,osterior (<sually associated

I, aE&, E%, E9

II, III, aE7

with Inferior or &ateral but can E=, EH, EJ be isolated) 2ight entricular (<sually associated with Inferior)

As the myocardial infarction e ol es, there may be loss of 2 wa e height and de elopment of pathological G wa es. T wa e in ersion may persist for months or e en permanently following acute myocardial infarction. Typically, howe er, the T wa e reco ers, lea ing a pathological G wa e as the only remaining e idence that an acute myocardial infarction has occurred.

. Ca!dia ma!ke!s' +ardiac markers or cardiac enFymes are proteins from cardiac tissue found in the blood. These proteins are released into the bloodstream when damage to the heart occurs, as in the case of a myocardial infarction. <ntil the 0JH$s, the enFymes ;48T and &'* were used to assess cardiac inCury. Then it was found that disproportional ele ation of the MD subtype of the enFyme creatine kinase (+5) was ery specific for myocardial inCury. +urrent guidelines are generally in fa or of troponin sub)units I or T, which are ery specific for the heart muscle and are thought to rise before permanent inCury de elops. 3le ated troponins in the setting of chest pain may accurately predict a high likelihood of a myocardial infarction in the near future. The diagnosis of myocardial infarction re-uires two out of three components (history, 3+4, and enFymes). .hen damage to the heart occurs, le els of cardiac markers rise o er time, which is why blood tests for them are taken o er a /# hour period. Decause these enFyme le els are not ele ated immediately following a heart attack, patients presenting with chest pain are generally treated with the assumption that a myocardial infarction has occurred and then e aluated for a more precise diagnosis. d. Angiog!ap"y'

Angiogram of the coronary arteries. In difficult cases or in situations where inter ention to restore blood flow is appropriate, coronary angiography can be performed. A catheter is inserted into an artery (usually the femoral artery) and pushed to the essels supplying the heart. 8bstructed or narrowed arteries can be identified, and angioplasty applied as a therapeutic measure (see below). Angioplasty re-uires extensi e skill,

especially in emergency settings, and may not always be a ailable out of hours. It is commonly performed by inter entional cardiologists.

e. Histopat"ology'

Microscopy image (magn. ca 0$$x, *M3 stain) from autopsy specimen of myocardial infarct (= days post)infarction). *istopathological examination of the heart may re eal infarction at autopsy. <nder the microscope, myocardial infarction presents as a circumscribed area of ischemic, coagulati e necrosis (cell death). 8n gross examination, the infarct is not identifiable within the first 0/ hours. Although earlier changes can be discerned using electron microscopy, one of the earliest changes under a normal microscope are so)called wa y fibers. ;ubse-uently, the myocyte cytoplasm becomes more eosinophilic (pink) and the cells lose their trans ersal striations, with typical changes and e entually loss of the cell nucleus. The interstitium at the margin of the infarcted area is initially infiltrated with neutrophils, then with lymphocytes and macrophages, which phagocytose ((eat() the myocyte debris. The necrotic area is surrounded and progressi ely in aded by granulation tissue, which will replace the infarct with a fibrous (collagenous) scar (which are typical steps in wound healing).

The interstitial space (the space between cells outside of blood essels) may be infiltrated with red blood cells These features can be recogniFed in cases where the perfusion was not restored@ reperfused infarcts can ha e other hallmarks, such as contraction band necrosis. I. (anagement Immediate a!e' .hen symptoms of myocardial infarction occur, people wait on a erage of ? hours, instead of doing what is recommended> calling for help immediately. Acting immediately by calling the emergency ser ices can pre ent sustained damage to the heart ((time is muscle(). +ertain positions allow the patient to rest in a position which minimiFes breathing difficulties. A half)sitting position with knees bent is often recommended. Access to more oxygen can be gi en by opening the window and widening the collar for easier breathing. Aspirin can be gi en -uickly (if the patient is not allergic to aspirin)@ but taking aspirin before calling the emergency medical ser ices may be associated with unwanted delay. Aspirin has an antiplatelet effect which inhibits formation of further thrombi (blood clots) that clog arteries. Aon) enteric coated or soluble preparations are preferred. If chewed or dissol ed, respecti ely, they can be absorbed by the body e en -uicker. If the patient cannot swallow, the aspirin can be used sublingually. <.;. guidelines recommend a dose of 09/ I ?/% mg. Australian guidelines recommend a dose of 0%$ I ?$$ mg. 4lyceryl trinitrate (nitroglycerin) sublingually (under the tongue) can be gi en if it has been prescribed for the patient. If an A3' is a ailable the rescuer should immediately bring the A3' to the patientBs side and be prepared to follow its instructions should the ictim lose consciousness. If possible the rescuer should obtain basic information from the ictim, in case the patient is unable to answer -uestions once emergency medical technicians arri e (if the patient becomes unconscious). The ictimBs name and any information regarding the nature of the ictims pain will useful to health care pro iders. Also the exact time that these symptoms started, what the patient was

doing at the onset of symptoms, and anything else that might gi e clues to the pathology of the chest pain. It is also ery important to relay any actions that ha e been taken, such as the number or dose of aspirin or nitroglycerin gi en, to the 3M; personnel. 8ther general first aid principles include monitoring pulse, breathing, and le el of consciousness and, if possible, the blood pressure of the patient. In case of cardiac arrest, cardiopulmonary resuscitation (+,2) can be administered. A)tomati e%te!nal defi&!illation *AED+' ;ince the publication of data showing that the a ailability of automated external defibrillators (A3's) in public places may significantly increase chances of sur i al, many of these ha e been installed in public buildings, public transport facilities, and in non)ambulance emergency ehicles (e.g. police cars and fire engines). A3's analyFe the heartBs rhythm and determine whether the rhythm is amenable to defibrillation ((shockable(), as in entricular tachycardia and entricular fibrillation. Eme!gen y se!,i es' 3mergency Medical ;er ices (3M;) ;ystems ary considerably in their ability to e aluate and treat patients with suspected acute myocardial infarction. ;ome pro ide as little as first aid and early defibrillation. 8thers employ highly trained paramedics with sophisticated technology and ad anced protocols. 3arly access to 3M; is promoted by a J)0)0 system currently a ailable to J$: of the population in the <nited ;tates. Most are capable of pro iding oxygen, IE access, sublingual nitroglycerine, morphine, and aspirin. ;ome are capable of pro iding Thrombolytic therapy in the prehospital setting. .ith primary ,+I emerging as the preferred therapy for ;T segment ele ation myocardial infarction, 3M; can play a key role in reducing door to balloon inter als (the time from presentation to a hospital 32 to the restoration of coronary artery blood flow) by performing a 0/ lead 3+4 in the field and using this information to triage the patient to the most appropriate medical facility. In addition, the 0/ lead 3+4 can be transmitted to the recei ing hospital, which enables time sa ing decisions to be made prior to the patientBs arri al. This may include a (cardiac alert( or (;T3MI alert( that calls in off duty personnel in areas where the cardiac cath lab is not staffed /# hours a day. 3 en

in the absence of a formal alerting program, prehospital 0/ lead 3+4s are independently associated with reduced door to treatment inter als in the emergency department. I. T!eatment A heart attack is a medical emergency which demands both immediate attention and acti ation of the emergency medical ser ices. The ultimate goal of the management in the acute phase of the disease is to sal age as much myocardium as possible and pre ent further complications. As time passes, the risk of damage to the heart muscle increases@ hence the phrase that in myocardial infarction, (time is muscle(, and time wasted is muscle lost. The treatments itself may ha e complications. If attempts to restore the blood flow are initiated after a critical period of only a few hours, the result is reperfusion inCury instead of amelioration. 8ther treatment modalities may also cause complications@ the use of antithrombotics for example carries an increased risk of bleeding. a. #i!st line 8xygen, aspirin, glyceryl trinitrate (nitroglycerin) and analgesia (usually morphine, hence the popular mnemonic M8AA, morphine, oxygen, nitro, aspirin) are administered as soon as possible. In many areas, first responders can be trained to administer these prior to arri al at the hospital. 8f the first line agents, only aspirin has been pro en to decrease mortality. 8nce the diagnosis of myocardial infarction is confirmed, other pharmacologic agents are often gi en. These include beta blockers, anticoagulation (typically with heparin), and possibly additional antiplatelet agents such as clopidogrel. These agents are typically not started until the patient is e aluated by an emergency room physician or under the direction of a cardiologist. These agents can be used regardless of the reperfusion strategy that is to be employed. .hile these agents can decrease mortality in the setting of an acute myocardial infarction, they can lead to complications and potentially death if used in the wrong setting. &. Repe!f)sion The concept of reperfusion has become so central to the modern treatment of acute myocardial infarction, that we are said to be in the reperfusion era. ,atients who present with suspected acute

myocardial infarction and ;T segment ele ation (;T3MI) or new bundle branch block on the 0/ lead 3+4 are presumed to ha e an occlusi e thrombosis in an epicardial coronary artery. They are therefore candidates for immediate reperfusion, either with Thrombolytic therapy, percutaneous coronary inter ention (,+I) or when these therapies are unsuccessful, bypass surgery. Indi iduals without ;T segment ele ation are presumed to be experiencing either unstable angina (<A) or non);T segment ele ation myocardial infarction (A;T3MI). They recei e many of the same initial therapies and are often stabiliFed with antiplatelet drugs and anticoagulant. If their condition remains (hemodynamically) stable, they can be offered either late coronary angiography with subse-uent restoration of blood flow (re asculariFation), or non)in asi e stress testing to determine if there is significant ischemia that would benefit from re asculariFation. If hemodynamic instability de elops in indi iduals with A;T3MIs, they may undergo urgent coronary angiography and subse-uent re asculariFation. The use of Thrombolytic agents is contraindicated in this patient subset, howe er. The basis for this distinction in treatment regimens is that ;T segment ele ations on an 3+4 are typically due to complete occlusion of a coronary artery. 8n the other hand, in A;T3MIs there is typically a sudden narrowing of a coronary artery with preser ed (but diminished) flow to the distal myocardium. Anticoagulation and antiplatelet agents are gi en to pre ent the narrowed artery from occluding. At least 0$: of patients with ;T3MI donBt de elop myocardial necrosis (as e idenced by a rise in cardiac markers) and subse-uent - wa es on 354 after reperfusion therapy. ;uch a successful restoration of flow to the infarct)related artery during an acute myocardial infarction is known as (aborting( the myocardial infarction. If treated within the hour, about /%: of ;T3MIs can be aborted. . T"!om&olyti t"e!apy Thrombolytic therapy is indicated for the treatment of ;T3MI if the drug can be administered within 0/ hours of the onset of symptoms, the patient is eligible based on exclusion criteria, and primary ,+I is not immediately a ailable. The effecti eness of Thrombolytic therapy is highest in the first / hours. After 0/ hours, the risk associated with Thrombolytic therapy outweighs any benefit. Decause irre ersible inCury occurs within /I# hours of the infarction, there is a limited window of time a ailable for reperfusion to work.

Thrombolytic drugs are contraindicated for the treatment of unstable angina and A;T3MI and for the treatment of indi iduals with e idence of cardiogenic shock. Although no perfect Thrombolytic agent exists, an ideal Thrombolytic drug would lead to rapid reperfusion, ha e a high sustained patency rate, be specific for recent thrombi, be easily and rapidly administered, create a low risk for intra)cerebral and systemic bleeding, ha e no antigenicity, ad erse hemodynamic effects, or clinically significant drug interactions, and be cost effecti e. +urrently a ailable Thrombolytic agents include streptokinase, urokinase, and alteplase (recombinant tissue plasminogen acti ator, rt,A). More recently, Thrombolytic agents similar in structure to rt,A such as reteplase and tenecteplase ha e been used. These newer agents boast efficacy at least as good as rt,A with significantly easier administration. The Thrombolytic agent used in a particular indi idual is based on institution preference and the age of the patient. 'epending on the Thrombolytic agent being used, adCu ant anticoagulation with heparin or low molecular weight heparin may be of benefit. .ith t,A and related agents (reteplase and tenecteplase), heparin is needed to maintain coronary artery patency. Decause of the anticoagulant effect of fibrinogen depletion with streptokinase and urokinase treatment, it is less necessary there. Intracranial bleeding (I+D) and subse-uent cerebro ascular accident (+EA) is a serious side effect of Thrombolytic use. The risk of I+D is dependent on a number of factors, including a pre ious episode of intracranial bleed, age of the indi idual, and the Thrombolytic regimen that is being used. In general, the risk of I+D due to Thrombolytic use for the treatment of an acute myocardial infarction is between $.% and 0 percent. Thrombolytic therapy to abort a myocardial infarction is not always effecti e. The degree of effecti eness of a Thrombolytic agent is dependent on the time since the myocardial infarction began, with the best results occurring if the Thrombolytic agent is used within an hour of the onset of symptoms.N If the indi idual presents more than 0/ hours after symptoms commenced, the risk of intracranial bleed are considered higher than the benefits of the Thrombolytic agent. 7ailure rates of Thrombolytic can be as high as /$: or higher. In cases of failure of the Thrombolytic agent to open the infarct)related coronary artery, the patient is then either treated conser ati ely with anticoagulants or allowed to (complete the infarction( or percutaneous coronary inter ention (,+I, see below) is then performed. ,ercutaneous coronary inter ention in this setting is known as (rescue ,+I( or (sal age ,+I(. +omplications, particularly bleeding, are significantly higher with rescue ,+I than with primary ,+I due to the action of the Thrombolytic agent.

Pe! )taneo)s o!ona!y inte!,ention>

Thrombus material (in a cup, upper left corner) remo ed from a coronary artery during a percutaneous coronary inter ention to abort a myocardial infarction. 7i e pieces of thrombus are shown (arrow heads). Although clinical trials suggest better outcomes compared to Thrombolytic therapy, logistic and economic obstacles seem to hinder a more widespread application of percutaneous coronary inter ention (,+I) ia cardiac catheteriFation. The use of percutaneous coronary inter ention as a therapy to abort a myocardial infarction is known as primary ,+I. The goal of primary ,+I is to open the artery as soon as possible and preferably within J$ minutes of the patient presenting to the emergency room. This time is referred to as the door)to)balloon time. 7ew hospitals can pro ide ,+I within the J$ minute inter al. The current guidelines in the <nited ;tates restrict primary ,+I to hospitals with a ailable emergency bypass surgery as a backup, but this is not the case in other parts of the world. ,rimary ,+I in ol es performing a coronary angiogram to determine the anatomical location of the infarcting essel, followed by balloon angioplasty (and fre-uently deployment of an intracoronary stent) of the thrombosis arterial segment. In some settings, an extraction catheter may be used to attempt to aspirate (remo e) the thrombus prior to balloon angioplasty. .hile the uses of intracoronary stents do not impro e the short term outcomes in primary ,+I, the use of stents is widespread because of the decreased rates of procedures to treat restenosis compared to balloon angioplasty. AdCu ant therapy during primary ,+I includes intra enous heparin, aspirin, and clopidogrel. The uses of glycoprotein IIb!IIIa inhibitors are often used in the setting of primary ,+I to reduce the risk of ischemic complications during the procedure. 'ue to the number of antiplatelet agents and

anticoagulants used during primary ,+I, the risk of bleeding associated with the procedure are higher than during an electi e ,+I. d. Co!ona!y a!te!y &ypass s)!ge!y

+oronary artery bypasses surgery during mobiliFation (freeing) of the right coronary artery from its surrounding tissue, adipose tissue (yellow). The tube isible at the bottom is the aortic cannula (returns blood from the *&M). The tube abo e it (obscured by the surgeon on the right) is the enous cannula (recei es blood from the body). The patientBs heart is stopped and the aorta is cross)clamped. The patientBs head (not seen) is at the bottom. 'espite the guidelines, emergency bypass surgery for the treatment of an acute myocardial infarction (MI) is less common then ,+I or medical management. In an analysis of patients in the <.;. Aational 2egistry of Myocardial Infarction (A2MI) from Oanuary 0JJ% to May /$$#, the percentage of patients with +ardiogenic shock treated with primary ,+I rose from /=.#: to %#.#:, while the increase in +AD4 treatment was only from /.0: to ?./:. 3mergency coronary artery bypass graft surgery (+AD4) is usually undertaken to simultaneously treat a mechanical complication, such as a ruptured papillary muscle, or a entricular septal defect, with ensueing +ardiogenic shock. In uncomplicated MI, the mortality rate can be high when the surgery is performed immediately following the infarction. If this option is entertained, the patient should be stabiliFed prior to surgery, with supporti e inter entions such as the use of an intra)aortic balloon pump. In patients de eloping +ardiogenic shock after a myocardial infarction, both ,+I and +AD4 are satisfactory treatment options, with similar sur i al rates.

+oronary artery bypass surgery in ol es an artery or ein from the patient being implanted to bypass narrowings or occlusions on the coronary arteries. ;e eral arteries and eins can be used@ howe er internal mammary artery grafts ha e demonstrated significantly better long)term patency rates than great saphenous ein grafts. In patients with two or more coronary arteries affected, bypass surgery is associated with higher long)term sur i al rates compared to percutaneous inter entions In patients with single essel disease, surgery is comparably safe and effecti e, and may be a treatment option in selected cases. Dypass surgery has higher costs initially, but becomes cost)effecti e in the long term. A surgical bypass graft is more in asi e initially but bears less risk of recurrent procedures (but these may be again minimally in asi e). ". (onito!ing fo! a!!"yt"mias Additional obCecti es are to pre ent life)threatening arrhythmias or conduction disturbances. This re-uires monitoring in a coronary care unit and protocolised administration of antiarrhythmic agents. Antiarrhythmic agents are typically only gi en to indi iduals with life)threatening arrhythmias after a myocardial infarction and not to suppress the entricular ectopy that is often seen after a myocardial infarction. i. Re"a&ilitation +ardiac rehabilitation aims to optimiFe function and -uality of life in those afflicted with a heart disease. This can be with the help of a physician, or in the form of a cardiac rehabilitation program. ,hysical exercise is an important part of rehabilitation after a myocardial infarction, with beneficial effects on cholesterol le els, blood pressure, weight, stress and mood. ;ome patients become afraid of exercising because it might trigger another infarct. ,atients are stimulated to exercise, and should only a oid certain exerting acti ities such as sho eling. &ocal authorities may place limitations on dri ing motoriFed ehicles. ;ome people are afraid to ha e sex after a heart attack. Most people can resume sexual acti ities after ? to # weeks. The amount of acti ity needs to be dosed to the patients possibilities. -. Se onda!y p!e,ention The risk of a recurrent myocardial infarction decreases with strict blood pressure management and lifestyle changes, chiefly smoking cessation, regular exercise, a sensible diet for patients with heart disease, and limitation of alcohol intake.

,atients are usually commenced on se eral long)term medications post)MI, with the aim of pre enting secondary cardio ascular e ents such as further myocardial infarctions, congesti e heart failure or cerebro ascular accident (+EA). <nless contraindicated, such medications may include>

Antiplatelet drug therapy such as aspirin and!or clopidogrel should be continued to reduce the risk of pla-ue rupture and recurrent myocardial infarction. Aspirin is first)line, owing to its low cost and comparable efficacy, with clopidogrel reser ed for patients intolerant of aspirin. The combination of clopidogrel and aspirin may further reduce risk of cardio ascular e ents@ howe er the risk of hemorrhage is increased.

Deta blocker therapy such as metoprolol or car edilol should be commenced. These ha e been particularly beneficial in high)risk patients such as those with left entricular dysfunction and!or continuing cardiac ischemia. P)Dlockers decrease mortality and morbidity. They also impro e symptoms of cardiac ischemia in A;T3MI.

A+3 inhibitor therapy should be commenced /#I#H hours post)MI in hemodynamically)stable patients, particularly in patients with a history of MI, diabetes mellitus, hypertension, anterior location of infarct (as assessed by 3+4), and!or e idence of left entricular dysfunction. A+3 inhibitors reduce mortality, the de elopment of heart failure, and decrease entricular remodelling post)MI.

;tatin therapy has been shown to reduce mortality and morbidity post)MI. The effects of statins may be more than their &'& lowering effects. The general consensus is that statins ha e pla-ue stabiliFation and multiple other ((pleiotropic() effects that may pre ent myocardial infarction in addition to their effects on blood lipids.

The aldosterone antagonist agent eplerenone has been shown to further reduce risk of cardio ascular death post)MI in patients with heart failure and left entricular dysfunction, when used in conCunction with standard therapies abo e.

8mega)? fatty acids, commonly found in fish, ha e been shown to reduce mortality post)MI. .hile the mechanism by which these fatty acids decrease mortality is unknown, it has been postulated that the sur i al benefit is due to electrical stabiliFation and the pre ention of entricular fibrillation.N0?%Q *owe er, further studies in a high)risk subset ha e not shown a clear) cut decrease in potentially fatal arrhythmias due to omega)? fatty acids.

Ne. t"e!apies )nde! in,estigation>

,atients who recei e stem cell treatment by coronary artery inCections of stem cells deri ed from their own bone marrow after a myocardial infarction (MI) show impro ements in left entricular eCection fraction and end)diastolic olume not seen with placebo. The larger the initial infarct siFe, the greater the effect of the infusion. +linical trials of progenitor cell infusion as a treatment approach to ;T ele ation MI are proceeding. There are currently ? biomaterial and tissue engineering approaches for the treatment of MI, but these are in an e en earlier stage of medical research, so many -uestions and issues need to be addressed before they can be applied to patients. The first in ol es polymeric left entricular restraints in the pre ention of heart failure. The second utiliFes in itro engineered cardiac tissue, which is subse-uently implanted in i o. The final approach entails inCecting cells and!or a scaffold into the myocardium to create in situ engineered cardiac tissue. /. Compli ations +omplications may occur immediately following the heart attack (in the acute phase), or may need time to de elop (a chronic problem). After an infarction, an ob ious complication is a second infarction, which may occur in the domain of another atherosclerotic coronary artery or in the same Fone if there are any li e cells left in the infarct. a. Congesti,e "ea!t fail)!e> A myocardial infarction may compromise the function of the heart as a pump for the circulation, a state called heart failure. There are different types of heart failure@ left) or right)sided (or bilateral) heart failure may occur depending on the affected part of the heart, and it is a low)output type of failure. If one of the heart al es is affected, this may cause dysfunction, such as mitral regurgitation in the case of left)sided MI. The incidence of heart failure is particularly high in patients with diabetes and re-uires special management strategies. &. (yo a!dial !)pt)!e> Myocardial rupture is most common three to fi e days after myocardial infarction, commonly of small degree, but may occur one day to three weeks later, in as many as 0$: of all MIs. This may occur in the free walls of the entricles, the septum between them, the papillary muscles, or less commonly the atria. 2upture occurs because of increased pressure against the weakened walls of the

heart chambers due to heart muscle that cannot pump blood out effecti ely. The weakness may also lead to entricular aneurysm, a localiFed dilation or ballooning of the heart chamber. 2isk factors for myocardial rupture include completion of infarction (no re asculariFation performed), female sex, ad anced age, and a lack of a pre ious history of myocardial infarction. The shear stress between the infarcted segment and the surrounding normal myocardium (which may be hypercontractile in the post)infarction period) makes it a nidus for rupture. 2upture is usually a catastrophic e ent that may result a life)threatening process known as cardiac tamponade, in which blood accumulates within the pericardium or heart sac, and compresses the heart to the point where it cannot pump effecti ely. 2upture of the intra entricular septum (the muscle separating the left and right entricles) causes a entricular septal defect with shunting of blood through the defect from the left side of the heart to the right side of the heart. 2upture of the papillary muscle may also lead to acute mitral regurgitation and subse-uent pulmonary edema and possibly e en +ardiogenic shock.

0ife1t"!eatening a!!"yt"mia>

A 0/ lead electrocardiogram showing entricular tachycardia. ;ince the electrical characteristics of the infarcted tissue change (see ,athophysiology section), arrhythmias are a fre-uent complication. The re)entry phenomenon may cause too fast heart rates ( entricular tachycardia and e en entricular fibrillation), and ischemia in the electrical conduction

system of the heart may cause a complete heart block (when the impulse from the sinoatrial node, the normal cardiac pacemaker, doesnBt reach the heart chambers any more). . Pe!i a!ditis> As a reaction to the damage of the heart muscle, inflammatory cells are attracted. The inflammation may reach out and affect the heart sac. This is called ,ericarditis. In 'resslerBs syndrome, this occurs se eral weeks after the initial e ent. d. Ca!diogeni s"o k> A complication that may occur in the acute setting soon after a myocardial infarction or in the weeks following it is cardiogenic shock. +ardiogenic shock is defined as a hemodynamic state in which the heart cannot produce enough of a cardiac output to supply an ade-uate amount of oxygenated blood to the tissues of the body. .hile the data on performing inter entions on indi iduals with +ardiogenic shock is sparse, trial data suggests a long)term mortality benefit in undergoing re asculariFation if the indi idual is less than =% years old and if the onset of the acute myocardial infarction is less than ?9 hours and the onset of +ardiogenic shock is less than 0H hours. If the patient with cardiogenic shock is not going to be re asculariFed, aggressi e hemodynamic support is warranted, with insertion of an intra)aortic balloon pump if not contraindicated. If diagnostic coronary angiography does not re eal a culprit blockage that is the cause of the cardiogenic shock, the prognosis is poor. 2. P!ognosis The prognosis for patients with myocardial infarction aries greatly, depending on the patient, the condition itself and the gi en treatment. <sing simple ariables which are immediately a ailable in the emergency room, patients with a higher risk of ad erse outcome can be identified. 7or example, one study found that $.#: of patients with a low risk profile had died after J$ days, whereas the mortality rate in high risk patients was /0.0:. Although studies differ in the identified ariables, some of the more reproduced risk stratifiers include age, hemodynamic parameters (such as heart failure, cardiac arrest on admission, systolic blood pressure, or 5illip class of two or greater), ;T)segment de iation, diabetes, serum creatinine concentration, peripheral ascular disease and ele ation of cardiac markers.

Assessment of left entricular eCection fraction may increase the predicti e power of some risk stratification models. The prognostic importance of G)wa es is debated. ,rognosis is significantly worsened if a mechanical complication (papillary muscle rupture, myocardial free wall rupture, and so on) were to occur. There is e idence that case fatality of myocardial infarction has been impro ing o er the years in all ethnicities.