ST elevation myocardial infarction

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Associate Editors-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]

Acute myocardial infarction is a type of acute coronary syndrome, which is most frequently (but not always) a manifestation of coronary artery disease. The acute coronary syndromes include ST segment elevation myocardial infarction (STEMI), non-ST segment elevation myocardial infarction (NSTEMI), and unstable angina (UA).

Depending on the location of the obstruction in the coronary circulation, different zones of the heart can become injured. Using the anatomical terms of location, one can describe anterior, inferior, lateral, apical and septal infarctions (and combinations, such as anteroinferior, anterolateral, and so on).^[1] For example, an occlusion of the left anterior descending coronary artery will result in an anterior wall myocardial infarct.^[2]

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.^[3] The inner part of the heart muscle is more vulnerable 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.^[2]

The phrases transmural and subendocardial infarction used to be considered synonymous with Q-wave and non-Q-wave myocardial infarction respectively, based on the presence or absence of Q waves on the ECG. It has since been shown that there is no clear correlation between the presence of Q waves with a transmural infarction and the absence of Q waves with a subendocardial infarction,^[4] but Q waves are associated with larger infarctions, while the lack of Q waves is associated with smaller infarctions. The presence or absence of Q-waves also has clinical importance,^[5] with improved outcomes associated with a lack of Q waves.^[6]

The phrase “massive heart attack” is not a recognized medical term.

• acute coronary syndrome
• angina
• Cardiac arrest
• coronary thrombosis
• Hibernating myocardium
• Stunned myocardium
• Ventricular remodeling

• The MD TV: Comments on Hot Topics, State of the Art Presentations in Cardiovascular Medicine, Expert Reviews on Cardiovascular Research
• Clinical Trial Results: An up to dated resource of Cardiovascular Research
• Risk Assessment Tool for Estimating Your 10-year Risk of Having a Heart Attack – based on information of the Framingham Heart Study, from the United States National Heart, Lung and Blood Institute
• Heart Attack – overview of resources from MedlinePlus.
• Heart Attack Warning Signals from the Heart and Stroke Foundation of Canada
• Regional PCI for STEMI Resource Center – Evidence based online resource center for the development of regional PCI networks for acute STEMI
• STEMI Systems – Articles, profiles, and reviews of the latest publications involved in STEMI care. Quarterly newsletter.
• American College of Cardiology (ACC) Door to Balloon (D2B) Initiative.
• American Heart Association’s Heart Attack web site – Information and resources for preventing, recognizing and treating heart attack.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]

ST elevation myocardial infarction is largely influenced by the role of plaque rupture.

Atherosclerosis, or hardening of the arteries, is the gradual buildup of cholesterol and fibrous tissue (collagen and smooth muscle cells) throughout the vascular tree. When there is localized accumulation of lipids and scar tissue, this is called a “plaque”. Somewhat paradoxically, it is not the most severe plaque narrowing that leads to ST elevation MI. Pathological studies indicate that it is often mild-to-moderate, lipid-laden, inflamed plaques that are the ones most likely to rupture and cause an ST elevation MI (STEMI) or a non ST elevation MI (NSTEMI). ^[1] The role of plaque rupture in STEMI and NSTEMI is supported by studies demonstrating that plaque rupture is present in about 70% and superficial erosion is present in 30% of patients who die suddenly in whom there is documented coronary artery disease. ^[2] Exposure of the blood stream to the thrombogenic components of the plaque leads to activation of the coagulation cascade and thrombus formation. In STEMI, the clot completely occludes the epicardial artery, and there is a complete lack of blood flow to the involved territory. This causes transmural injury and ST elevation. In NSTEMI, there is partial obstruction with embolization. This causes ischemia and subendocardial injury that are manifested by ST depression.

1. Macrophage accumulation has been shown to be present to a greater degree in patients with acute coronary syndromes than in those patients with chronic stable angina ^{[3] [4]} These activated macrophages can release enzymes such as metalloproteinases, interstitial collagenase, gelatinase, and stromelysin that degrade collagen, elastin, and proteoglycans. ^[5] This enzymatic degradation in turn leads to breakdown of the fibrous cap. The thin shoulders or edges of the fibrous cap appear to be particularly vulnerable to erosion and breakdown.
2. Neovascularization of the plaque Moreno et have shown that microvessel density was increased in ruptured plaques when compared with nonruptured plaques (P=0.0001). Furthermore, among lesions with severe macrophage infiltration at the fibrous cap, microvessel density was increased (P=0.0001) was well as at the edges or shoulders of the plaque (P=0.0001). Intraplaque hemorrhage was also associated with an increase in microvessel density (P=0.04) as was the presence of thin-cap fibroatheromas (P=0.038). Microvessel density at the base of the plaque was identified as an independent (P=0.003) correlate of plaque rupture. ^[6]
3. High oscillatory shear stress
4. Vasoconstriction
5. Spontaneous coronary dissection

There are numerous systemic risk factors associated with thrombus formation following plaque rupture:

1. Smoking: Smoking increases platelet aggregation and plasma epinephrine levels ^[7]
2. Fibrinogen: Elevated levels of fibrinogen have been associated with thrombosis including abnormal levels of fibrinogen ^[8]
3. Von Willebrand factor antigen ^[8]
4. Tissue plasminogen activator ^[8]
5. Anticardiolipin antibodies ^[9]
6. Cross-linked fibrin-degradation products ^[10]
7. Polymorphisms of a platelet glycoprotein receptor ^[11]

Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology

Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology

In 1940, Blumgart ligated or tied off the coronary artery in dogs and cats and for the first time demonstrated a wavefront of cell death folllowing vessel occlusion ^{[12] [13] [14] [15] [16]}

Irreversible injury of ischemic myocytes occurs first in the subendocardial zone. With more extended ischemia, a wavefront of cell death moves through the myocardium to involve progressively more of the transmural thickness of the ischemic zone. The precise location, size, and specific morphologic features of an acute myocardial infarction depend on:

1. The location, severity, and rate of development of coronary atherosclerotic obstructions,
2. The size of the vascular bed perfused by the obstructed vessels
3. The duration of the coronary artery occlusion
4. The metabolic / oxygen needs of the myocardium at risk,
5. The extent of collateral blood vessels

Decrease of ATP levels in myocytes in reaction to ischemia starts within seconds and causes loss of contractility in first two minutes. If ischemia persists, ATP levels reduced to its half level within 10 minutes and to 1/10 within 40 minutes. Irreversible cell injury occurs between 20-40 minutes and microvascular level injury starts if ischemia lasts more than an hour.^[17]

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. Recent studies indicate that another form of cell death called apoptosis also plays a role in the process of tissue damage subsequent to myocardial infarction.^[18] As a result, the patient’s heart can be permanently damaged. This scar tissue also puts the patient at risk for potentially life threatening arrhythmias.

In ST segment myocaridal infarction (STEMI), the ST segments on the ECG are by definition elevated and there is myonecrosis (death of myocytes) as reflected by elevation of biomarkers such as creatine kinase MB fraction (CK-MB) or troponin T or I (tn). The ST segments are elevated due to full thickness injury of the myocardium.

The following are excellent videos demonstrating the underlying pathophysiology. {{#ev:youtube|L6EiPLli5x8}} {{#ev:youtube|cOMzh2hf_Vw}} {{#ev:youtube|a8Idk4EUYTs}}

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ogheneochuko Ajari, MB.BS, MS [2]

The most common proximate cause of ST elevation myocardial infarction is plaque rupture. There are risk factors for plaque rupture and triggers of plaque rupture. A full discussion regarding the chronic risk factors and acute triggers of ST elevation MI can be found in other chapters. While plaque rupture is the most common cause of ST segment elevation MI, other conditions can cause ST elevation and myocardial necrosis. In order to expeditiously treat an alternate underlying cause of myonecrosis, it is important to rapidly identify conditions other than plaque rupture that may also cause ST elevation and myonecrosis. Indeed, the management of some of these conditions might differ substantially from that of plaque rupture: cocaine induced STEMI would not be treated with beta-blockers, and myocardial contusion would not be treated with an antithrombin.

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated.

• Aortic dissection
• Carbon monoxide poisoning
• Disseminated intravascular coagulation
• Infectious endocarditis

• Plaque rupture

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]

ST segment myocardial infarction must be differentiated from other conditions that cause ST elevation and chest pain.

Acute epicardial artery occlusion by thrombus is certainly one cause of ST segment elevation, but other causes of ST segment elevation which are not associated with myonecrosis include the following:^[1][2][3]

• Aneurysm of the ventricle can result in persistent ST segment elevation that can be exacerbated with tachycardia
• Arrhythmogenic right ventricular cardiomyopathy
• Balloon inflation in a coronary artery during percutaneous coronary intervention
• Brugada syndrome
• Transthoracic cardioversion
• Coronary artery rupture during percutaneous coronary intervention
• Early repolarization is a normal variant that can result in ST segment elevation. It is more common in males of younger age. The ST elevation is exacerbated by bradycardia.
• Hyperkalemia known as the “dialyzable current of njury” hyperkalemia may cause hyperacute ECG changes due to changes in membrane polarity
• Left bundle branch block is associated with ST segment elevation in those leads that are discordant to the QRS. Stated differently, if the QRS is predominantly of a negative deflection, it is normal to observe ST segment elevation in the same leads. The presence of ST elevation in leads where the QRS deflection is upright (concordance) may be a marker of myocardial injury.
• Myopericarditis can cause injury to the subepicardial myocytes and ST segment elevation.
• Myocarditis can cause injury to the subepicardial myocytes and ST segment elevation.
• Pericardiocentesis when the needle comes into contact with the myocardium, there can be ST segment elevation reflecting local injury of the myocardium.
• Pericarditis can cause injury to the subepicardial myocytes and ST elevation.
• Pulmonary Embolism
• Prinzmetal’s angina is associated with ST segment elevation due to transient epicardial coronary artery spasm either in the absence or presence of atherosclerosis. If the condition persists long enough, myonecrosis can be observed.
• Intracranial hemorrhage (stroke) can in some cases cause ST segment elevation due to direct myocyte injury from a hyper-adrenergic stimulation emanating from the central nervous system.

While plaque rupture is the most common cause of ST segment elevation MI, other conditions can cause ST elevation and myocardial necrosis. In order to expeditiously treat an alternate underlying cause of myonecrosis, it is important to rapidly identify conditions other than plaque rupture that may also cause ST elevation and myonecrosis. Indeed, the management of some of these conditions might be differ substantially from that of plaque rupture: cocaine induced STEMI would not be treated with beta-blockers, and myocardial contusion would not be treated with an antithrombin. These conditions include the following:

ST elevation MI is one of several life threatening causes of chest pain that must be distinguished from each other.

• Aortic dissection
• Esophageal rupture
• Myocardial infarction
• Pulmonary embolism
• Tension pneumothorax

The frequency of conditions exclusive of acute myocardial infarction in a decreasing order is:^[8]

• Gastroesophageal disease
• Ischemic heart disease (angina, not myocardial infarction)
• Chest wall syndromes

Thorough history including: onset, duration, type of pain, location, exacerbating factors, alleviating factors, and radiation. Risk factors for coronary artery disease: family history, smoking, hyperlipidemia, and diabetes.

• Actinomycosis
• Acute intermittent porphyria
• Adenosine
• Amonafide
• Anemia
• Ankylosing spondylitis
• Aortic valve stenosis
• Arsenic trioxide
• Arsenicals
• Blood transfusion and complications
• Bornholm disease
• Bronchogenic cyst
• Carbon monoxide toxicity
• Cardiomyopathy
• Familial hypertrophic cardiomyopathy
• Cardiopulmonary resuscitation
• Coronary artery dissection
• Diffuse esophageal spasm
• Dissecting aortic aneurysm
• Dressler syndrome
• Pleural empyema
• Esophageal achalasia
• Esophageal cyst
• Fabry disease
• Functional disorders
• Gastric ulcer
• Gastroesophageal reflux
• Gemeprost
• Glatiramer acetate
• Glycogenosis type 7
• Ischaemic heart disease
• Kawasaki disease
• Left ventricular hypertrophy
• Lymphangiomyomatosis
• Mediastinitis
• Mesothelioma
• Mitral valve prolapse
• Myocardial infarction
• Myocarditis
• Naratriptan
• Nylidrin
• Esophageal foreign body
• Esophageal rupture
• Esophagitis
• Pericarditis
• Pleural effusion
• Pleural fibroma
• Pleuritis
• Pneumonia
• Pneumothorax
• Porfimer
• Prinzmetal angina
• Pulmonary embolism
• Pulmonary infarction
• Quaternary syphilis
• Recurrent hereditary polyserositis
• Regadenoson
• Respiratory alkalosis
• Rib fracture
• Rib pain
• Rizatriptan
• Rumination disorder
• SAPHO syndrome
• Shingles
• Sickle cell crisis (thrombotic)
• Sickle cell disease
• Acute spinal cord injury
• Subdiaphragmatic abscess
• Sumatriptan
• Syndrome X
• Tabes dorsalis
• Takotsubo cardiomyopathy
• Tension pneumothorax
• Thallium
• Thyroiditis
• Tietze costochondritis
• Trichinella spiralis
• Unstable angina
• Varicella-zoster virus
• Wegener granulomatosis
• Zolmitriptan

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editors-In-Chief: Yuri B. Pride, M.D. [2] ; Cafer Zorkun, M.D., Ph.D. [3]

Myocardial infarction is a common presentation of ischemic heart disease. The World Heart Organization (WHO) estimated in 2002 that, 12.6 percent of deaths worldwide were from ischemic heart disease.

Ischemic heart disease is the leading cause of death in developed countries, but third to AIDS and lower respiratory infections in developing countries.^[1]

Over 9 million patients in the United States alone have angina. An estimated 80,700,000 American adults (one in three) have one or more types of cardiovascular disease (CVD), of whom 38,200,000 are estimated to be age 60 or older. Except as noted, the estimates were extrapolated to the U.S. population in 2005 from NHANES 1999–2004. (Total CVD includes diseases in the bullet points below except for congenital heart disease). Due to overlap, it is not possible to add these conditions to arrive at a total. ^{[2] [3][4]}

• Hypertension: 73,000,000
• Coronary heart disease: 16,000,000

• Myocardial infarction: 8,100,000
• Angina pectoris: 9,100,000

• Heart failure: 5,300,000
• Stroke: 5,800,000
• Congenital heart disease: 650,000 – 1,300,000

This means that roughly every 65 seconds, an American dies of a coronary event.

Although it is difficult to ascertain the true incidence of ST elevation myocardial infarction (STEMI), according to the ACC/AHA guidelines, a conservative estimate is that approximately 500,000 patients suffer STEMI each year ^[5]. The incidence of STEMI has decreased over time. In an observational study of 5,832 metropolitan patients spanning from 1975 to 1997, the incidence of STEMI decreased from 171/100,000 to 101/100,000 ^[6]

The following prevalence estimates are for people age 18 and older from NCHS/NHIS, 2005: ^[7]

• Among whites only, 12.0% have heart disease, 6.6% have CHD, 21.0% have hypertension and 2.3% have had a stroke.
• Among blacks, 10.2% have heart disease, 6.2% have CHD, 31.2% have hypertension and 3.4% have had a stroke.
• Among Hispanics or Latinos, 8.3% have heart disease, 5.9% have CHD, 20.3% have hypertension and 2.2% have had a stroke.
• Among Asians, 6.7% have heart disease, 3.8% have CHD, 19.4% have hypertension and 2.0% have had a stroke.
• Among Native Hawaiians or other Pacific Islanders, 22.4% have hypertension (other prevalence estimates considered unreliable).

The mortality among patients who suffer STEMI has progressively declined in recent years. From 1975 to 1997, one observational study reported that the in-hospital mortality decreased from 24% to 14% ^[6]. In the Global Registry of Acute Coronary Events (GRACE), a multinational cohort study that includes 16,814 patients with STEMI were enrolled and followed up in 113 hospitals in 14 countries between 1999 and 2006, in-hospital mortality declined from 8.4% in 1999 to 4.6% in 2005 ^[8].

The reason for this decline in mortality is likely multifactorial and includes, but is certainly not limited to, decline in symptom onset-to-presentation time, more widespread use of primary PCI ^[9], improvements in time to reperfusion (door-to-needle and door-to-balloon times) ^[10][11] and improved medical therapy, including increases in the use of evidence-based therapies such as aspirin ^[12], beta blockers^{[13] [14]}, clopidogrel ^[15], statins ^[16] and angiotension converting enzyme inhibitors or angiotensin receptor blockers ^[17].

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]

In these chapters on ST elevation, the word risk factors refers to those epidemiologic and genetic variables that expose someone to a higher risk of developing atherosclerotic plaque. The word triggers refer to those factors in the patients immediate history or environment that may have lead to rupture of the atherosclerotic plaque.

Muller et al have developed the following nomenclature to categorize and analyze data pertaining to triggers of MI ^[1]:

(1) Trigger: An activity that produces short-term physiological changes that may lead directly to onset of acute CVD.

(2) Acute risk factor: A short-term physiological change, such as a surge in arterial pressure or heart rate, an increase in coagulability, or vasoconstriction, that follows a trigger and may result in disease onset.

(3) Hazard period: The time interval after trigger initiation associated with an increased risk of disease onset because of the trigger. The onset and offset times of the hazard period, which could also be designated a “vulnerable period,” may be sharply defined, as in heavy exertion, or less well defined, as with respiratory infection. The duration of the hazard period may also vary, eg from < 1 hour during heavy physical exertion to weeks or months with bereavement.

(4) Triggered acute risk prevention (TARP): Cardiovascular risk reduction that focuses on the short-term increase in risk associated with a trigger.

Risk factors for atherosclerosis are generally risk factors for myocardial infarction:

• Advancing age
• Male gender^[3]
• Cigarette smoking
• Hypercholesterolemia (more accurately hyperlipoproteinemia, especially high low density lipoprotein and low high density lipoprotein)
• Diabetes (with or without insulin resistance)
• High blood pressure
• Obesity^[4] (defined by a body mass index of more than 30 kg/m², or alternatively by waist circumference or waist-hip ratio).
• Elevated homocysteine

• Mendelian inherited conditions

Familial mixed hyperlipidaemia

LDL receptor deficiency

• Autosomal dominant conditions

Pseudoxanthoma elasticum dominant type 1

• Autosomal recessive conditions

Cystathionine beta-synthase deficiency

Sitosterolemia

According to present trends in the United States, half of healthy 40-year-old males and 1 in 3 healthy 40-year-old women will develop coronary artery disease (CAD) in the future.^[5] This chance is greater when a family history of heart disease is involved.

Studies have reported that the risk of CAD increases two- to sevenfold when there is a genetic link. ^[6] The studies by Nora and Nora (1978a) evaluated a large number of patients with congenital heart disease.^[7] Results show that about 8% of the defects were primarily genetics-related, 2% were environmental (caused by drugs, viruses, maternal nutrition, maternal metabolism, or fetal hemodynamics) and 90% were multifactorial (due to a combination of environmental and genetic factors). The study also noted that there is a two- to threefold increase in the recurrence risk for congenital heart disease when two of the family members are affected. This is particularly the case when the parent is severely affected or when the affected members are child and parent. The risk for a myocardial infarction is two to three times greater in a first-degree relative than in a person with no family history of heart disease. This fact speaks in particular to the early presentation of CAD in patients with no other risk factors. Second cousins have a 1 in 23 chance of sharing a particular gene and third cousins have a 1 in 128 likelihood.

Genetic hypertension and hyperlipidemia are strong predictors of familial heart disease.^[8] Hypertensive people are twice as likely to have a family history of the condition than are normotensives. Genetic hypertension is an example of a polygenic mode of inheritance that reflects cellular sodium transport defects and an abnormal response to psychogenic stress. There is indication that Pheochromocytoma, a rare cause of hypertension, may be familial as well.

• Diabetes mellitus type 2 (NIDDM)
• Primary hyperparathyroidism

• Systemic lupus erythematosus (SLE)

Socioeconomic factors such as a shorter education and lower income (particularly in women), and living with a partner may also contribute to the risk of MI.^[9] To understand epidemiological study results, it’s important to note that many factors associated with MI mediate their risk via other factors. For example, the effect of education is partially based on its effect on income and marital status.^[9]

Women who use combined oral contraceptive pills have a modestly increased risk of myocardial infarction, especially in the presence of other risk factors, such as smoking.^[10]

Inflammation is known to be an important step in the process of atherosclerotic plaque formation.^[11] C-reactive protein (CRP) is a sensitive but non-specific marker for inflammation. Elevated CRP blood levels, especially measured with high sensitivity assays, can predict the risk of MI, as well as stroke and development of diabetes.^[11] Moreover, some drugs for MI might also reduce CRP levels.^[11] The use of high sensitivity CRP assays as a means of screening the general population is advised against, but it may be used optionally at the physician’s discretion, in patients who already present with other risk factors or known coronary artery disease.^[12] Whether CRP plays a direct role in atherosclerosis remains uncertain.^[11]

Inflammation in periodontal disease may be linked coronary heart disease, and since periodontitis is very common, this could have great consequences for public health.^[13] Serological studies measuring antibody levels against typical periodontitis-causing bacteria found that such antibodies were more present in subjects with coronary heart disease.^[14] Periodontitis tends to increase blood levels of CRP, fibrinogen and cytokines;^[15] thus, periodontitis may mediate its effect on MI risk via other risk factors.^[16] Preclinical research suggests that periodontal bacteria can promote aggregation of platelets and promote the formation of foam cells.^[17][18] A role for specific periodontal bacteria has been suggested but remains to be established.^[19]

Baldness, hair greying, a diagonal earlobe crease^[20] and possibly other skin features are independent risk factors for MI. Their role remains controversial; a common denominator of these signs and the risk of MI is supposed, possibly genetic.^[21]

While family history, along with age and sex, is uncontrollable^[3], many of the risk factors for heart disease can be eliminated by maintaining a healthy lifestyle. In fact, a person’s daily habits significantly affect the risk of heart disease due to genetic predisposition. Studies have shown that deaths can be avoided by attending to the controllable risk factors. Such risk factors include: obesity, blood pressure, cigarette smoking and plasma cholesterol.^[22]

A study published in Circulation shines some light on the importance of eliminating these controllable risk factors in people with a family history of heart disease. Data demonstrated that in men with a genetic link to heart disease, an estimated 68% of the excess deaths were due to the addition of smoking, a modifiable risk factor; concluding that the risk of heart disease in men with a family history of the condition is significantly related to the additional risk factors he accumulates.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Several factors have been associated with an increased risk of developing ST elevation myocardial infarction (STEMI). These factors include physical exertion, psychological stress, sexual activity, diurnal (daily) variations in cortisol and platelet aggregation and circannual (yearly) variations in lipids and infectious etiologies, exposure to pollution and or particulate matter, cocaine and ingestion of a recent fatty meal.

Muller et al have developed the following nomenclature to categorize and analyze data pertaining to triggers of MI ^[1]:

(1) Trigger: An activity that produces short-term physiological changes that may lead directly to onset of acute CVD.

(2) Acute risk factor: A short-term physiological change, such as a surge in arterial pressure or heart rate, an increase in coagulability, or vasoconstriction, that follows a trigger and may result in disease onset.

(3) Hazard period: The time interval after trigger initiation associated with an increased risk of disease onset because of the trigger. The onset and offset times of the hazard period, which could also be designated a “vulnerable period,” may be sharply defined, as in heavy exertion, or less well defined, as with respiratory infection. The duration of the hazard period may also vary, eg from < 1 hour during heavy physical exertion to weeks or months with bereavement.

(4) Triggered acute risk prevention (TARP): Cardiovascular risk reduction that focuses on the short-term increase in risk associated with a trigger.

In the following sections, you will read that certain triggers are associated with a dramatic rise in the relative risk of having an MI (e.g. heavy exertion among patients with a sedentary lifestyle increases their risk of an MI 107 fold). These dramatic increases in relative risk, must, however, be placed in the appropriate clinical context.

It must be born in mind that while triggers are frequent events, MI or sudden death are relatively infrequent events. The risk of sudden death with exercise provides a nice example. The relative risk of sudden death within 30 minutes after >/= 6 METS of exercise goes up 16.9 fold. However, because sudden death is so infrequent, this translates into 1 sudden cardiac death for every 1.51 million episodes of heavy exertion. ^[2] The number of absolute events is even lower among nurses in the Nurses Health Study undertaking mild to meoderate exertion: 1 sudden death for every 36.5 hours of exertion. ^[3]

While the presence of triggers increases the relative risk of MI dramatically, the absolute number of MIs attributable to the trigger may be quite low.

A dramatic rise in the relative risk of a very, very, very infrequent event therefore translates clinically into a very small rise in the absolute number of events attributable to the trigger.

Physical exertion, especially if the exertion is much more intense than the individual usually performs has been associated with the onset of STEMI. ^{[4][5][6] [7] [8][2][3][9]} The ONSET study demonstrated that intense exertion (defined as >/= 6 metabolic equivalents of METS) within the previous hour was associated with a 5.9 fold rise in the risk of MI ^[6].

Studies linking physical exertion to MI:

• The ONSET Study: Relative risk = 5.9 ^[6]
• The Stockholm Heart Epidemiology Program (SHEEP): Relative risk = 6.1 ^[7]
• The Triggers and Mechanisms of Myocardial Infarction (TRIMM) study: Relative risk = 2.1 ^[4]

Blizzards have often been cited as a trigger of MI, and the physical exertion of snow shoveling has frequently been cited as a contributor. ^{[10] [11]}

Impact of a sedentary lifestyle: The relative risk of MI quoted above increases dramatically among those individuals who lead a sedentary lifestyle. For those in poor physical condition, the relative risk was 107 fold higher in the ONSET study. In contrast, among those individuals who reported that they engaged in physical activity 5 days a week or more, the risk was only doubled.

Mechanism: It has been hypothesized that exertion increases blood pressure, pulse and oscillatory shear which in turn may increase the risk of plaque rupture.

While the above discussion pertains to documented nonfatal MI, approximately a quarter of MI patients may die of sudden death or fatal MI before reaching the hospital. In a cohort of 21,481 male physicians in the United States who by self report who had no prior history of coronary artery disease, there was a 16.9 fold rise in the risk of sudden cardiac death within 30 minutes of intense exertion (>/= 6 METS) ^[2]. Similar to what has been reported with respect to the onset of MI, there was no increase in the risk of sudden death with heavy exertion among those nurses who exercised more than 2 hours per week.

Psychological stress associated with anger ^[12], work related stressful events ^[13], wartime bombing ^{[14] [15]} , earthquakes ^[16] and other natural disasters has been associated with an increased risk of onset of myocardial infarction.

Intense anger (fist / teeth clenched) has been associated with a risk in the risk of MI in the 2 hours following the episode in the following studies:

• ONSET: 2.3 fold rise^[12]
• SHEEP: 9 fold rise^[17]
• Kotton et al: 14 fold rise^[18]

The psychosocial stressors that precipitated the anger were as follows:

• Argument with family members (25%)
• Conflicts at work (22%)
• Legal problems (8%)

If a patient is in the >75th percentile for anxiety, this increases the relative risk of MI 1.6 fold for the 2 hours following the period of anxiety.^[12]

Stress cardiomyopathy which is also known as Left Ventricular Apical Ballooning Syndrome, Takotsubo cardiomyopathy, or Ampulla-shaped cardiomyopathy is a cardiac syndrome characterized by a reversible transient apical ventricular dysfunction. Since the cardiomyopathy is often triggered by emotional stress, such as the death of a loved one, the condition is sometimes also referred to as the Broken Heart Syndrome. In 2006, the syndrome was renamed Stress Cardiomyopathy, and was classified as an acquired cardiomyopathy. ^[19]

The typical presentation of someone with takotsubo cardiomyopathy is a sudden onset of congestive heart failure or chest pain associated with EKG changes suggestive of an anterior wall acute MI. During the course of evaluation of the patient, a bulging out of the left ventricular apex with a hypercontractile base of the left ventricle is often noted. It is the hallmark bulging out of the apex of the heart with preserved function of the base that earned the syndrome its name “tako tsubo”, or octopus trap in Japan, where it was first described. Evaluation of individuals with takotsubo cardiomyopathy typically include a coronary angiogram, which does not reveal any significant blockages that would cause the left ventricular dysfunction. Provided that the individual survives their initial presentation, the left ventricular function improves within days to weeks^[20]. Takotsubo cardiomyopathy is more commonly seen in post-menopausal women^[21]. Often there is a history of a recent severe emotional or physical stress.^[21]

An aggressive timeline or deadline at work has been associated with a rise in the risk of MI:

• The SHEEP study: 6 fold rise
• The ONSET study: 2.3 fold rise

The stress of firing an employee has been associated with a rise in the risk of MI:

• The ONSET study: 2.2 fold rise

Natural disasters have been associated with an increased risk of MI. The best documented association has been with earthquakes. For instance the 1994 earthquake in Los Angeles was associated with a 4 fold rise in the risk of sudden death and a 35% rise in the relative risk of a non-fatal MI. ^{[22] [23]} It is notable that the association of earthquakes with MI is variable depending upon the time of day that the earthquake occurs. The LA earthquake occurred just after 4 A.M., just when platelet aggregation may be at a peak (see below). However, the earthquake that struck San Francisco Bay in 1989 at 5 P.M. was not associated with an increased risk of MI. ^[24]

Within 50 miles of the world trade center, there was a 49% increase in the relative risk of an MI in the 60 days following the 9/11 attack: There were 118 MIs in the 60 days after the attack versus 79 MIs in the 60 days before (p=0.01). How much of this is attributable to particulate matter versus psychological stress is not clear. ^[25]

The stress of missile attacks has been associated with a doubling in the risk of non fatal MI and sudden death. ^[26]

The stress of sporting events has been associated with an increased risk of MI in a population. An example that has been cited is the 50% increase in the risk of MI or stroke among Dutch men associated with the loss of Holland to France in the 1996 European football finals. It is notable that no such rise in risk was observed among Dutch women or the French. ^{[27] [28]} The World Cup of soccer has been associated with a doubling of MI incidence. ^[29]

The association of sexual activity with the onset of MI may represent components of physical exertion as well as psychologic stress. In both the SHEEP and the ONSET studies, recent sexual activity increased the risk of MI by 2.5 fold ^[30][31]. Again, to place this relative risk into clinical context, it should be noted that only 3% of MI patients had had sexual intercourse within the past 2 hours prior to the onset of MI. It should also be noted that the increase in risk of MI with sexual activity did not differ between patients with and without a history of coronary artery disease.

The risk of MI with sexual intercourse is a frequent concern among patients who have coronary artery disease. Again, the data above indicates that recent sexual activity doubles the risk of an MI, and this may on the surface appear to be disconcerting to both a patient and healthcare professional. But again, to place this relative risk into context, the absolute risk must be taken into account. The average risk of an MI in a patient at average risk has been estimated to be about 1 chance in a million during any given hour during middle age. Sexual activity increases that risk to 2 in a million per hour for the 2 hours after sexual intercourse. If the annual risk of MI is about 1%, weekly sexual intercourse will increase this annual risk to just 1.01%. ^[32] As is the case with physical exertion, regular exercise (6 METS >/= 3 times per week) reduced the relative risk of MI with sexual intercourse from 3.0 to 1.2 in the ONSET study.^[30]

Thus, because the risk is small, because the frequency of sexual activity is relatively small, and because the period of increased risk is short (approximately 2 hours) the absolute risk of MI associated with sexual intercourse is quite small.

Exposure to high levels of ambeint air pollution (exposure to fine particulate matter in the past 2 – 24 hours) has been associated with a transient elevation in the risk of myocardial infarction ^[33]. There is a rise in CRP and plasma viscosity following exposure to fine particulate matter and it has been speculated that the pulmonary inflammation that follows such exposure may trigger a systemic state of hypercoagulability ^[34][35]. Exposure to fine particulate matter has also been associated with changes in autonomic tone manifested by sinus tachycardia ^{[36] [37]}, as well as a reduction in heart rate variability ^{[38] [39] [40]}. Finally, ventricular arrhythmias as manifested by firing of AICDs has been associated with exposure to fine particulate matter ^[41].

Acute severe infection, such as pneumonia, can trigger myocardial infarction ^[42]. A more controversial link is that between Chlamydophila pneumoniae infection and atherosclerosis^[43]. While this intracellular organism has been demonstrated in atherosclerotic plaques, evidence is inconclusive as to whether it can be considered a causative factor^[43].Treatment with antibiotics in patients with proven atherosclerosis has not demonstrated a decreased risk of heart attacks or other coronary vascular diseases.^[44]

There have been reports of a 4 fold rise in the risk of MI following a heavy meal. ^[45]

This rise in risk may account for a second peak in the circadian variation in the onset of MI around 8 P.M. in the evening. The mechanism underlying the association is not clear. It has been speculated that ingestion of a heavy fatty meal may be associated with a rise in prothrombotic factors and heart rate, and a reduction in vascular reactivity. ^{[46] [47]}

Ingestion of cocaine has been associated with STEMI ^[48].

Marijuana use has been associated with a 4.8 fold rise in the risk of MI. ^[49]

Most MIs occur in the early morning hours when cortisol and adrenaline rise and platelets are more activated. This diurnal variation is obliterated with aspirin therapy, pointing to the putative role of platelets in the initiation of MI. ^{[50] [51] [52] [53] [54] [55] [56]}

When a creful history is obtained, approximately half (48%) of MI patients will report a trigger ^[57]. It is notable that 13% of patients will report that there were of 2 or more triggers. The following triggers were most commonly associated with the onset of MI in the Multicenter Investigation of Limitation of Infarct Size (MILIS) study ^[57]:

1. Emotional upset (18%)
2. Moderate physical activity (14%)
3. Heavy physical activity (9%)
4. Lack of sleep (8%)
5. Overeating (7%)

Following the sudden death of Tim Russert of NBC’s Meet the Press on June 13th 2008, many laypeople and physicians alike have asked “what are the triggers of a sudden heart attack”? Barbara Walters speculated that Tim Russert may have died from “the stress of the job”. Others were concerned about a recent weight gain and lack of sleep. This chapter reviews the literature pertaining to triggers of acute MI.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Without treatment, ST elevation myocardial infarction can prove fatal. Complications of ST elevation MI are divided into the following categories: ischemic, mechanical, arrythmic, embolic, and pericarditis. The prognosis for patients with myocardial infarction varies greatly depending upon simple demographic variables like age, infarct artery location, the presence of signs and symptoms of heart failure on presentation, the symptom to door time, and comorbidities that are present. Several risk stratification tools have been developed to predict a patient’s mortality. Most of these risk scores are based upon clinical data obtained at the time of admission rather than at the time of discharge.

Reinfarction or reocclusion of the infarct-related artery is associated with a doubling of mortality.^[1] Unfortunately, it is difficult to predict who will reinfarct following fibrinolytic therapy. Among patients undergoing primary PCI, bivalirudin monotherapy has been associated with stent thrombosis in the HORIZONS-AMI and EUROMAX trials.^[2][3] Aggressive antiplatelet and antithrombotic therapy minimizes the risk of reinfarction.

A new murmur in patients with ST elevation myocardial infarction should raise an immediate concern of mechanical complicaitons such as papillary muscle rupture, septal rupture, and free-wall rupture which portend a dismal prognosis and may be differentiated on the basis of physical and echocardiographic findings or hemodynamic profiles. Other mechanical sequelae include true or false ventricular aneurysm, dynamic left ventricular outflow tract obstruction, cardiogenic shock, and heart failure.

• A true left ventricular aneurysm is an outpouching formed by a stretched, thinned-out myocardial scar. Patients with transmural infarction and patients who do not receive reperfusion therapy are at increased risk. LV aneurysm may manifest acutely as low-output cardiogenic shock or chronically as heart failure or thromboembolism in the presence of mural thrombus. A large, diffuse point of maximal impulse and S₃ gallops may be evident on physical examination. A chest radiograph may demonstrate a localized bulging segment in the cardiac silhouette. Dyskinetic or paradoxical motions of the aneurysmal segment may be detected by echocardiography or ventriculography. True aneurysm connects with the LV cavity by a wide neck and is less susceptible to rupture than a false aneurysm. ACE inhibitor and vasodilator are used in the mangement of chronic heart failure associated with ventricular aneurysm. Anticoagulant is indicated in the presence of mural thrombus. Sustained ventricular arrhythmia from an aneurysm may require defibrillator placement. Surgical resection may be considered in selected cases with refractory symptoms.

• In contrast to the true aneurysm which contains viable myocardium in its wall, pseudoaneurysm lacks the myocardial elements and is formed by adherent pericardium and organized hematoma. Unlike true ventricular aneurysm, pseudoaneurysm communicates with the cavity of the left ventricle through a narrow neck and is more prone to rupture. Pseudoaneurysm may partially reduce stroke volume similar to a true aneurysm. Surgery is recommended for all patients regardless of symptoms or the size of pseudoaneurysm in light of a high risk for spontaneous rupture and sudden death.

• Papillary muscle rupture is characterized by symptoms of acute severe mitral regurgitation and pulmonary edema and should be suspected in STEMI patients with a new soft holosystolic murmur at the apex. Posterior papillary muscle rupture, as occurs in inferior MI, is more common than anterior papillary muscle rupture which may be a complication of anterior or lateral MI. Posterior papillary muscle is considered more susceptible to ischemic rupture due to its singular blood supply from the posterior descending artery. In contradistinction to the posterior papillary muscle, the anterior papillary muscle receives a dual blood supply from the left anterior descending artery and the circumflex artery.^[4] Urgent transthoracic echocardiography should be obtained to establish a definite diagnosis. Nitroglycerin or nitroprusside may be used to temporize the patient if systolic blood pressure is above 90 mm Hg. If the patient cannot tolerate vasodilator due to rapid hemodynamic deterioration, intra-aortic balloon counterpulsation should be instituted as a bridging therapy until emergency mitral valve replacement can be performed.

• Patients with septal rupture frequently report chest pain, shortness of breath, and symptoms of low-output cardiogenic shock. Key physical findings include a harsh, loud holosystolic murmur best heard at the lower left sternal border, palpable thrill at the right precordium, S₃ gallops, and accentuation of pulmonic component of the second heart sound. Color Doppler echocardiography is useful for determining the location and size of the defect and detecting left-to-right shunt and right ventricular overload. Septal rupture should be managed by temporary stabilization with intra-aortic balloon counterpulsation followed by intravenous vasodilator and early surgical closure.

• Free-wall rupture usually leads to hemopericardium and abrupt circulatory collapse. Clinical manifestations range from anginal, pleuritic, or pericardial chest discomfort to catastrophic symptoms of cardiogenic shock, cardiac tamponade, and sudden death. Echocardiography is useful for the diagnosis and emergency pericardiocentesis may be indicated for cardiac tamponade. Survival depends primarily on early recognition and prompt surgical repair.

New onset atrial fibrillation in the setting of STEMI is associated with a very poor prognosis ^[6]. New onset atrial fibrillation is likely a marker for left atrial distension due to impaired left ventricular compliance.

• Atrial flutter
• Postinfarction conduction abnormalities

• Sudden cardiac death

• Stroke
• DVT

• Post myocardial infarction pericarditis
• Dressler’s syndrome

• 2013 Revised ACCF/AHA Guidelines for the Management of ST-Elevation Myocardial Infarction ^[7]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Five variables explain 90% of the prognosis in STEMI: Advanced age,sinus tachycardia, reduced systolic blood pressure, heart failure or Killip class of two or greater, and anterior myocardial infarction location. Two main risk-stratification scores are used when assessing a patient with ST elevation MI and acute coronary syndromes; the TIMI Risk Score (for STEMI), and the GRACE risk score (for acute coronary syndrome.

While we as physicians often labor under the impression that we can dramatically change a patient’s prognosis, it is noteworthy that 90% of the predictive information regarding 30 day mortality is contained in the following 5 baseline variables that can be modified to only a limited degree: ^[1]

1. Advanced age
2. Sinus tachycardia
3. Reduced systolic blood pressure
4. Heart failure or Killip class of two or greater
5. Anterior myocardial infarction location

Sinus tachycardia, hypotension, Killip class, and anterior MI are all essentially markers of poor pump function on admission. These risk factors for 30 day mortality have been well validated in a multivariate analysis of 41,020 patients in the GUSTO-I trial. Advanced age was the most significant factor associated with higher 30-day mortality. The rate was only 1.1% in the youngest decile (< 45 years) and climbed to 20.5% in patients > 75 (adjusted chi 2 = 717, P < .0001). Other variables most closely associated with an increased risk of mortality were lower systolic blood pressure at randomization (chi 2 = 550, P < .0001), higher Killip class (chi 2 = 350, P < .0001), elevated heart rate (chi 2 = 275, P < .0001), and the presence of an anterior infarction (chi 2 = 143, P < .0001). When taken together, these five baseline characteristics contained 90% of the prognostic information. Other significant though less important factors included previous myocardial infarction, height, time to treatment, diabetes, weight, smoking status, type of thrombolytic, previous bypass surgery, hypertension, and prior cerebrovascular disease. When these variables were combined, a validated model was created which stratified patients according to their mortality risk and accurately estimated the likelihood of death.

Other risk factors include, serum creatinine concentration ^[2], and peripheral vascular disease.^[3][4]

Assessment of left ventricular ejection fraction may increase the predictive power of some risk stratification models.^[5] The prognostic importance of Q-waves is debated.^[6] Prognosis is significantly worsened if a mechanical complication (papillary muscle rupture, myocardial free wall rupture, and so on) were to occur.

There is evidence that case fatality of myocardial infarction has been improving over the years in all ethnicities.^[7]

Interestingly, although tobacco abuse is a risk factor for CAD and STEMI, smoking is associated with a lower risk of mortality among patients who present with STEMI ^[8][9] This is due, at least in part, to the finding that smokers who present with STEMI are, on average, at least a decade younger than non-smokers. Smokers more often have involvement of the right coronary artery rather than the left anterior descending artery as well. Smokers paradoxically have better myocardial perfusion following reperfusion therapy than non smokers ^[10].

The Thrombolysis in Myocardial Infarction TIMI Risk Score ^[11] and TIMI Risk Index ^[12] are two prognostic indices that have been validated in clinical trials and epidemiologic studies to predict 30-day mortality among patients with STEMI.

The TIMI risk score for STEMI was created from simple arithmetic sum of independent predictors of mortality weighted according to the adjusted odds ratios from logistic regression analysis. The risk score was derived from 14,114 patients enrolled in the Intravenous nPA for Treatment of Infarcting Myocardium Early II trial (TIME II). The TIMI risk score was subsequently validated in an unselected heterogeneous community population through the National Registry of Myocardial Infarction (NRMI) 3 & 4. The TIMI Risk Score incorporates eight clinical variables (age, systolic blood pressure [SBP], heart rate [HR], Killip class, anterior ST elevation or left bundle branch block on electrocardiogram, diabetes mellitus, history of hypertension or angina, low weight and time to treatment >4 hours) and assigns them a point value based on their odds ratio for mortality.

The TIMI Risk Score was developed and validated in clinical trials of fibrinolytic therapy, but it has also been reported to be prognostic in community-based real-world registries ^[13] as well as elderly patients ^[14]. The TIMI risk score for TIMI is calculated by adding the numbers assigned to the different criteria shown below. The total possible score is 14.^[11]

The TIMI Risk Index incorporates age, HR and SBP (HR x [age/10] x 2/SBP), and has been validated in unselected patients ^[15], registries ^[16] and population-based cohorts ^[17]

• The Global Registry of Acute Coronary Events (GRACE) risk score for ACS:
  • The GRACE risk score was created from a multivariable logistic regression model using ACS patients enrolled in the GRACE registry (N=11389).
  • The GRACE risk score was validated using subsequent cohort of patients enrolled in GRACE (n=3972) and the Global Use of Strategies to Open Occluded Coronary Arteries IIb (GUSTO-IIb) trial (n=12142).

The total GRACE risk score is calculated by adding the points assigned to the different variable shown below. The highest total possible score 363.^[18]

A nomogram for the probability in-hospital mortality has been developed based on the GRACE score. Shown below is the probability of in-hospital mortality by the corresponding GRACE score value.^[18]

The total GRACE risk score is calculated by adding the points assigned to the different variable shown below.^[19] The highest total possible score 263.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Physiological changes during pregnancy may increase the woman’s risk of developing a myocardial infarction (MI). MI during the antepartum period is usually caused by an atherosclotic plaque rupture, whereas MI during the peripartum and postpartum period is usually caused by coronary artery dissection (commonly in the LAD). Diagnosis of MI among pregnant women is similar to that in the general population and requires clinical suspiccion, as well as ECG changes and troponin elevation. In contrast, elevated CK-MB concentration is unreliable, since CK-MB may normally increase during labor and post-delivery due to non-cardiac causes, namely placental and uterine leaks. During an MI, echocardiography is safe and may be performed to evaluate wall motion abnormalities, and fetal monitoring is recommended. Treatment is usually by percutaneous coronary intervention. If spontaneous coronary artery dissection occurs, a more thorough investigation for connective tissue diseases and vasculitis is warranted.

• Incidence: 1 per 35,000 deliveries
• Maternal mortality rate: 5% to 18%, fetal mortality rate: 9%
• Common in third trimester until 1-2 months post-delivery

• Antepartum: Atherosclotic plaque rupture is the most common cause
• Perpartum or postpartum: Coronary artery dissection (LAD > RCA > LC > LM)

• It is unknown if pregnancy itself is a risk factor in development of acute MI.
• The most important risk factors in the development of AMI in pregnancy are generally similar to those in the general population. Risk factors include:

• Age > 35 years
• Diabetes mellitus
• Hypertension
• Smoking
• Connective tissue diseases (e.g. Ehler Danlos syndrome)
• Vasculitis (e.g. Takayasu arteritis)
• Thrombophilia (e.g. antiphospholipid syndrome)
• Acute post-partum stress:

• Severe post-partum hemorrhage
• Post-partum infection

• During pregnancy, progesterone release results in structural changes in the vascular intima and media.
• Physiologically, cardiac output and blood volume increase during pregnancy, both of which may increase the risk of cardiovascular events.

• Diagnosis similar to the general population by: Symptoms, ECG changes, and troponin.
• CK-MB concentrations may markedly increase during labor and post-delivery due to non-cardiac causes, namely placental and uterine leaks.

• To view common normal physiological changes on ECG in pregnancy (may mimic AMI), click here.
• To view normal physiological changes in biomarker concentrations during labor and delivery: for troponin, click here | for CK-MB, click here.

• Echocardiography is safe and may be performed to evaluate wall motion abnormalities.
• Fetal monitoring is recommended.

• Percutaneous coronary intervention
• If spontaneous coronary artery dissection occurs, a more thorough investigation for connective tissue diseases and vasculitis is warranted.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

The diagnosis of acute MI is based upon the occurence of clinical symptoms such as substernal chest pain, ECG changes such as ST elevation and a rise in the release of very specific biomarkers into the bloodstream that are normally only found in side the heart muscle cell (the myocyte).

The diagnosis can be confirmed at the time of autopsy or at the time of angiography if a closed artery is seen. A new clinical evidence based diagnostic and classification system has been introduced by Thygesen K, Alpert JS, White HD, et al. and jointly sponsored by the American College of Cardiology (ACC), American Heart Association (AHA), European Society of Cardiology (ESC), and the World Heart Federation (WHF).^[1]

The term myocardial infarction should be used when there is evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Under these conditions any one of the following criteria meets the diagnosis for acute myocardial infarction. ^[1]

Below are the criteria quoted from the Thygesen article:

1. Detection of rise and/or fall of cardiac biomarkers (preferably Troponin) with at least one of the following

   a. Symptoms of ischemia

   b. EKG changes indicative of ischemia as ST segment elevation of >_{_} 0.1 mV in at least 2 contiguous leads, or new left bundle branch block LBBB). If initial ECG is non-diagnostic, repeat at 5 to 10 min intervals.

   c. Development of pathological Q waves

   d. Imaging evidence of new viable myocardium or wall motion abnormality

2. Sudden unexpected cardiac death, including cardiac arrest, often with symptoms suggestive of myocardial ischemia, accompanied by presumably new ST segment elevation, or new LBBB, and/or evidence of fresh thrombus in a coronary artery by angiography and/or at autopsy, if death has occurred before blood samples could be obtained, or at a time before the appearance of cardiac biomarkers in the blood
3. In patients with normal baseline troponin values, a greater than 3 times increase above the 99th percentile of the upper limit of normal of cardiac biomarkers has been designated as the definition of PCI related myocardial infarction. A subtype related to documented stent thrombosis is recognized.
4. For patients with CABG surgery; (In patients with normal baseline troponin values) increases of cardiac biomarkers greater than 5 times, (> 5 times the 99th percentile upper limit of normal) and either new pathological Q waves or new LBBB or angiographically evidence of new graft or native vessel occlusion have been designated as defining CABG surgery related myocardial infarction.
5. Pathological findings of acute myocardial infarction.

If any of the following are present, then a diagnosis of prior myocardial infarction is established:^[1]

• Development of new pathological Q waves with or without symptoms
• 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.
• Pathological findings of healed or healing myocardial infarction.

Five types of MI are now recognized and classified as follows: ^[1]

• Type 1: Spontaneous myocardial infarction related to ischemia due to a primary coronary event, such as plaque erosion and/or rupture, fissuring, or dissection.

• Type 2: Myocardial infarction secondary to ischemia due to an imbalance of O₂ supply and demand, as from coronary spasm or embolism, anemia, arrhythmias, hypertension, or hypotension

• Type 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)

• Type 4:

a. Myocardial infarction associated with Percutaneous Coronary Interventions (PCI)

b. Myocardial infarction associated with documented stent thrombosis.

• Type 5: Myocardial infarction associated with Coronary Artery Bypass Graft surgery

For the main article on cardiac markers see the chapter on cardiac markers. For the main article on the diagnosis of STEMI, see the chapter on Clinical classification of acute myocardial infarction.

There have been several prior classification schemes for characterizing MI:

1. Transmural (necrosis of full thickness of ventricle) vs. non-transmural (necrosis of partial thickness of ventricle)

2. Q wave vs. non Q wave: Based upon the development of electrocardiographic Q waves representing electrically inert tissue.

3. ST elevation MI (STEMI) and Non ST elevation myocardial infarction (NSTEMI)

At one time it was thought that Transmural MI and Q wave MI were synonymous. However, not all Q wave MIs are transmural, and not all transmural MIs are associated with Q waves.

Likewise, not all ST elevation MIs go on to cause q waves. Non ST elevation MIs can result in q waves.

Thus, ST elevation MI should not be equated with transmural MI or q wave MI. Likewise, Non ST elevation MI should not be equated with non transmural MI or non q wave MI. These 3 designations reflect three separate but overlapping characterization schemes.

Cardiac markers or cardiac enzymes are proteins that are present in cardiac myocytes that should not be in the bloodstream. When cardiac injury occurs (such as in acute MI), these intracellular proteins are then released into the bloodstream. Along with the patient’s history and the electrocardiogram, the release of these enzymes forms the basis of the diagnosis of ST elevation myocardial infarction.

Until the 1980s, the enzymes SGOT and LDH were used to assess cardiac injury. In the early 1980s it was found that disproportional elevation of the MB subtype of the enzyme creatine kinase (CK) was very specific for myocardial injury. More recently, troponin has been used as an even more specific marker of myonecrosis. Current guidelines are generally in favor of troponin sub-units I or T, which are very specific for damage to myocytes.^{[2] [3][4]}

It is important to note that it may take hours for cardiac enzymes to rise following injury to the myocardium, and that cardiac biomarkers may not be elevated on presentation. For this reason, cardiac enzymes and ECGs are checked every 6 to 8 hours over the course of the first 24 hours to “rule out” acute MI. These enzyme measures over the first 24 hours are used to gauge the size of an MI: higer peak levels and a greater area under the curve of enzyme release are associated with larger MIs and poorer prognosis.

It is important to note that cardiac troponins are a marker of all heart muscle damage, not just myocardial infarction. There are other “false positive” causes of troponin elevation that directly or indirectly lead to heart muscle damage can also therefore increase troponin levels:^[6][7][8][9]

• Cardiac:
  • Acute aortic dissection
  • Aortic valve disease
  • Cardiac amyloidosis and other cardiac infiltrative disorders
  • Cardiac contusion
  • Cardiac surgery and heart transplant
  • Closure of atrial septal defects
  • Coronary artery vasospasm
  • Defibrillation
  • Dilated cardiomyopathy
  • Endocarditis
  • Endomyocardial biopsy
  • Heart failure
  • Hypertrophic cardiomyopathy
  • Hypotension
  • Myocarditis
  • Percutaneous coronary intervention
  • Pericarditis
  • Pulmonary hypertension
  • Radiofrequency ablation
  • Supraventricular tachycardia including atrial fibrillation
  • Takotsubo cardiomyopathy

• Non-cardiac:
  • ARDS
  • Critical illness, e.g. sepsis
  • Extensive burn
  • High-dose chemotherapy
  • Hypovolemia
  • Intracranial hemorrhage
  • Primary pulmonary hypertension
  • Pulmonary embolism
  • Pulmonary emphysema
  • Renal failure
  • Scorpion venom
  • Shock
  • Strenuous exercise (e.g. marathon)
  • Stroke
  • Subarachnoid hemorrhage
  • Sympathomimetic ingestion