Treatment of an MI is time-critical.Aspirin is an appropriate immediate treatment for a suspected MI.Nitroglycerin or opioids may be used to help with chest pain; however, they do not improve overall outcomes.Supplemental oxygen is recommended in those with low oxygen levels or shortness of breath. In a STEMI, treatments attempt to restore blood flow to the heart, and include percutaneous coronary intervention (PCI), where the arteries are pushed open and may be stented, or thrombolysis, where the blockage is removed using medications. People who have a non-ST elevation myocardial infarction (NSTEMI) are often managed with the blood thinner heparin, with the additional use of PCI in those at high risk. In people with blockages of multiple coronary arteries and diabetes, coronary artery bypass surgery (CABG) may be recommended rather than angioplasty. After an MI, lifestyle modifications, along with long term treatment with aspirin, beta blockers, and statins, are typically recommended.
Worldwide, about 15.9 million myocardial infarctions occurred in 2015. More than 3 million people had an ST elevation MI and more than 4 million had an NSTEMI. STEMIs occur about twice as often in men as women. About one million people have an MI each year in the United States. In the developed world the risk of death in those who have had an STEMI is about 10%. Rates of MI for a given age have decreased globally between 1990 and 2010. In 2011, a MI was one of the top five most expensive conditions during inpatient hospitalizations in the US, with a cost of about $11.5 billion for 612,000 hospital stays.
Myocardial infarction (MI) refers to tissue death (infarction) of the heart muscle (myocardium). It is a type of acute coronary syndrome, which describes a sudden or short-term change in symptoms related to blood flow to the heart. Unlike other causes of acute coronary syndromes, such as unstable angina, a myocardial infarction occurs when there is cell death, as measured by a blood test for biomarkers (the cardiac protein troponin or the cardiac enzyme CK-MB). When there is evidence of an MI, it may be classified as an ST elevation myocardial infarction (STEMI) or Non-ST elevation myocardial infarction (NSTEMI) based on the results of an ECG.
The phrase "heart attack" is often used non-specifically to refer to a myocardial infarction and to sudden cardiac death. An MI is different from—but can cause—cardiac arrest, where the heart is not contracting at all or so poorly that all vital organs cease to function, thus causing death. It is also distinct from heart failure, in which the pumping action of the heart is impaired. However, an MI may lead to heart failure.
Signs and symptoms
Areas where pain is experienced in myocardial infarction, showing common (dark red) and less common (light red) areas on the chest and back.
Chest pain is the most common symptom of acute myocardial infarction and is often described as a sensation of tightness, pressure, or squeezing. Pain radiates most often to the left arm, but may also radiate to the lower jaw, neck, right arm, back, and upper abdomen. The pain most suggestive of an acute MI, with the highest likelihood ratio, is pain radiating to the right arm and shoulder. Similarly, chest pain similar to a previous heart attack is also suggestive. The pain associated with MI is usually diffuse, does not change with position, and lasts for more than 20 minutes.Levine's sign, in which a person localizes the chest pain by clenching one or both fists over their sternum, has classically been thought to be predictive of cardiac chest pain, although a prospective observational study showed it had a poor positive predictive value. Pain that responds to nitroglycerin does not indicate the presence or absence of a myocardial infarction.
In women, myocardial infarctions can present with different symptoms. The classic presentation of chest pain occurs in about 50% of women. Women can also commonly back or neck pain, indigestion, heartburn, lightheadedness, shortness of breath, fatigue, nausea, or pain in the back of the jaw. These symptoms are often overlooked or mistaken for another condition.
Many risk factors for myocardial infarction are potentially modifiable, with the most important being tobacco smoking (including secondhand smoke). Smoking appears to be the cause of about 36% and obesity the cause of 20% of coronary artery disease. Lack of physical activity has been linked to 7–12% of cases. Less common causes include stress-related causes such as job stress, which accounts for about 3% of cases, and chronic high stress levels.
There is varying evidence about the importance of saturated fat in the development of myocardial infarctions. Eating polyunsaturated fat instead of saturated fats has been shown in studies to be associated with a decreased risk of myocardial infarction, while other studies find little evidence that reducing dietary saturated fat or increasing polyunsaturated fat intake affects heart attack risk. Dietary cholesterol does not appear to have a significant effect on blood cholesterol and thus recommendations about its consumption may not be needed.Trans fats do appear to increase risk. Acute and prolonged intake of high quantities of alcoholic drinks (3–4 or more) increases the risk of a heart attack.
Family history of ischemic heart disease or MI, particularly if one has a male first-degree relative (father, brother) who had a myocardial infarction before age 55 years, or a female first-degree relative (mother, sister) less than age 65 increases a person's risk of MI.
The risk of having a myocardial infarction increases with older age, low physical activity, and low socioeconomic status. Heart attacks appear to occur more commonly in the morning hours, especially between 6AM and noon. Evidence suggests that heart attacks are at least three times more likely to occur in the morning than in the late evening.Shift work is also associated with a higher risk of MI. And one analysis has found an increase in heart attacks immediately following the start of daylight saving time.
Calcium deposits in the coronary arteries can be detected with CT scans. Calcium seen in coronary arteries can provide predictive information beyond that of classical risk factors.High blood levels of the amino acid homocysteine is associated with premature atherosclerosis; whether elevated homocysteine in the normal range is causal is controversial.
The animation shows plaque buildup or a coronary artery spasm can lead to a heart attack and how blocked blood flow in a coronary artery can lead to a heart attack.
A myocardial infarction occurs when an atheroscleroticplaque slowly builds up in the inner lining of a coronary artery and then suddenly ruptures, causing catastrophic thrombus formation, totally occluding the artery and preventing blood flow downstream.
The most common cause of a myocardial infarction is the rupture of an atherosclerotic plaque on an artery supplying heart muscle. Plaques can become unstable, rupture, and additionally promote the formation of a blood clot that blocks the artery; this can occur in minutes. Blockage of an artery can lead to tissue death in tissue being supplied by that artery. Atherosclerotic plaques are often present for decades before they result in symptoms.
The gradual buildup of cholesterol and fibrous tissue in plaques in the wall of the coronary arteries or other arteries, typically over decades, is termed atherosclerosis. Atherosclerosis is characterized by progressive inflammation of the walls of the arteries. Inflammatory cells, particularly macrophages, move into affected arterial walls. Over time, they become laden with cholesterol products, particularly LDL, and become foam cells. A cholesterol core forms as foam cells die. In response to growth factors secreted by macrophages, smooth muscle and other cells move into the plaque and act to stabilize it. A stable plaque may have a thick fibrous cap with calcification. If there is ongoing inflammation, the cap may be thin or ulcerate. Exposed to the pressure associated with blood flow, plaques, especially those with a thin lining, may rupture and trigger the formation of a blood clot (thrombus). The cholesterol crystals have been associated with plaque rupture through mechanical injury and inflammation.
Drawing of the heart showing anterior left ventricle wall infarction
If impaired blood flow to the heart lasts long enough, it triggers a process called the ischemic cascade; the heart cells in the territory of the blocked coronary artery die (infarction), chiefly through necrosis, and do not grow back. A collagenscar forms in their place. When an artery is blocked, cells lack oxygen, needed to produce ATP in mitochondria. ATP is required for the maintenance of electrolyte balance, particularly through the Na/K ATPase. This leads to an ischemic cascade of intracellular changes, necrosis and apoptosis of affected cells.
Cells in the area with the worst blood supply, just below the inner surface of the heart (endocardium), are most susceptible to damage. Ischemia first affects this region, the subendocardial region, and tissue begins to die within 15–30 minutes of loss of blood supply. The dead tissue is surrounded by a zone of potentially reversible ischemia that progresses to become a full-thickness transmural infarct. The initial "wave" of infarction can take place over 3–4 hours. These changes are seen on gross pathology and cannot be predicted by the presence or absence of Q waves on an ECG. The position, size and extent of an infarct depends on the affected artery, totality of the blockage, duration of the blockage, the presence of collateral blood vessels, oxygen demand, and success of interventional procedures.
Myocardial infarctions are generally clinically classified into ST elevation MI (STEMI) and non-ST elevation MI (NSTEMI). These are based on changes to an ECG. STEMIs make up about 25 – 40% of myocardial infarctions. A more explicit classification system, based on international consensus in 2012, also exists. This classifies myocardial infarctions into five types:
Spontaneous MI related to plaque erosion and/or rupture, fissuring, or dissection
MI related to ischemia, such as from increased oxygen demand or decreased supply, e.g. coronary artery spasm, coronary embolism, anemia, arrhythmias, high blood pressure or low blood pressure
Sudden unexpected cardiac death, including cardiac arrest, where symptoms may suggest MI, an ECG may be taken with suggestive changes, or a blood clot is found in a coronary artery by angiography and/or at autopsy, but where blood samples could not be obtained, or at a time before the appearance of cardiac biomarkers in the blood
There are a number of different biomarkers used to determine the presence of cardiac muscle damage. Troponins, measured through a blood test, are considered to be the best, and are preferred because they have greater sensitivity and specificity for measuring injury to the heart muscle than other tests. A rise in troponin occurs within 2–3 hours of injury to the heart muscle, and peaks within 1–2 days. The level of the troponin, as well as a change over time, are useful in measuring and diagnosing or excluding myocardial infarctions, and the diagnostic accuracy of troponin testing is improving over time. One high-sensitivity cardiac troponin is able to rule out a heart attack as long as the ECG is normal.
Other tests, such as CK-MB or myoglobin, are discouraged. CK-MB is not as specific as troponins for acute myocardial injury, and may be elevated with past cardiac surgery, inflammation or electrical cardioversion; it rises within 4–8 hours and returns to normal within 2–3 days.Copeptin may be useful to rule out MI rapidly when used along with troponin.
A 12-lead ECG showing a STEMI. Elevation of the ST segment can be seen in some leads.
Electrocardiograms (ECGs) are a series of leads placed on a person's chest that measure electrical activity associated with contraction of heart muscle. The taking of an ECG is an important part in the workup of an AMI, and ECGs are often not just taken once, but may be repeated over minutes to hours, or in response to changes in signs or symptoms.
ECG readouts product a waveform with different labelled features. In addition to a rise in biomarkers, a rise in the ST segment, changes in the shape or flipping of T waves, new Q waves, or a new left bundle branch block can be used to diagnose an AMI. In addition, ST elevation can be used to diagnose an ST segment myocardial infarction (STEMI). A rise must be new in V2 and V3 ≥2 mm (0,2 mV) for males or ≥1.5 mm (0.15 mV) for females or ≥1 mm (0.1 mV) in two other adjacent chest or limb leads. ST elevation is associated with infarction, and may be preceded by changes indicating ischemia, such as ST depression or inversion of the T waves. Abnormalities can help localize the location of an infarct, based on the leads that are affected by changes. Early STEMIs may be preceded by peaked T waves. Other ECG abnormalities relating to complications of acute myocardial infarctions may also be evident, such as atrial or ventricular fibrillation.
Medical societies and professional guidelines recommend that the physician confirm a person is at high risk for myocardial infarction before conducting imaging tests to make a diagnosis, as such tests are unlikely to change management and result in increased costs. Patients who have a normal ECG and who are able to exercise, for example, do not merit routine imaging.
A myocardial infarction requires immediate medical attention. Treatment aims to preserve as much heart muscle as possible, and to prevent further complications. Treatment depends on whether the myocardial infarction is a STEMI or NSTEMI. Treatment in general aims to unblock blood vessels, reduce blot clot enlargement, reduce ischemia, and modify risk factors with the aim of preventing future MIs. In addition, the main treatment for myocardial infarctions with ECG evidence of ST elevation (STEMI) include thrombolysis or percutaneous coronary intervention, although PCI is also ideally conducted within 1–3 days for NSTEMI. In addition to clinical judgement, risk stratification may be used to guide treatment, such as with the TIMI and GRACE scoring systems.
The pain associated with myocardial infarction may be treated with nitroglycerin or morphine. Nitroglycerin (given under the tongue or intravenously) may improve the blood supply to the heart, and decrease the work the heart must do. It is an important part of therapy for its pain relief, despite there being no benefit to overall mortality. Morphine may also be used, and is effective for the pain associated with STEMI. The evidence for benefit from morphine on overall outcomes, however, is poor and there is some evidence of potential harm.
There is varying evidence on the mortality benefits in NSTEMI. A 2014 review of P2Y12 inhibitors such as clopidogrel found they do not change the risk of death when given to people with a suspected NSTEMI prior to PCI, nor do heparins change the risk of death. They do decrease the risk of having a further myocardial infarction.
Primary percutaneous coronary intervention (PCI) is the treatment of choice for STEMI if it can be performed in a timely manner, ideally within 90–120 minutes of contact with a medical provider. Some recommend it is also done in NSTEMI within 1–3 days, particularly when considered high-risk. A 2017 review, however, did not find a difference between early versus later PCI in NSTEMI.
If PCI cannot be performed within 90 to 120 minutes in STEMI then fibrinolysis, preferably within 30 minutes of arrival to hospital, is recommended. If a person has had symptoms for 12 to 24 hours evidence for effectiveness of thrombolysis is less and if they have had symptoms for more than 24 hours it is not recommended. Thrombolysis involves the administration of medication that activates the enzymes that normally dissolve blood clots. These medications include tissue plasminogen activator, reteplase, streptokinase, and tenecteplase. Thrombolysis is not recommended in a number of situations, particularly when associated with a high risk of bleeding or the potential for problematic bleeding, such as active bleeding, past strokes or bleeds into the brain, or severe hypertension. Situations in which thrombolysis may be considered, but with caution, include recent surgery, use of anticoagulants, pregnancy, and proclivity to bleeding. Major risks of thrombolysis are major bleeding and intracranial bleeding. Pre-hospital thrombolysis reduces time to thrombolytic treatment, based on studies conducted in higher income countries, however it is unclear whether this has an impact on mortality rates.
In the past, high flow oxygen was recommended for everyone with a possible myocardial infarction. More recently, no evidence was found for routine use in those with normal oxygen levels and there is potential harm from the intervention. Therefore, oxygen is currently only recommended if oxygen levels are found to be low or if someone is in respiratory distress.
If despite thrombolysis there is significant cardiogenic shock, continued severe chest pain, or less than a 50% improvement in ST elevation on the ECG recording after 90 minutes, then rescue PCI is indicated emergently.
Cardiac rehabilitation benefits many who have experienced myocardial infarction, even if there has been substantial heart damage and resultant left ventricular failure. It should start soon after discharge from the hospital. The program may include lifestyle advice, exercise, social support, as well as recommendations about driving, flying, sport participation, stress management, and sexual intercourse.
There is a large crossover between the lifestyle and activity recommendations to prevent a myocardial infarction, and those that may be adopted as secondary prevention after an initial myocardial infarction, because of shared risk factors and an aim to reduce atherosclerosis affecting heart vessels.
Physical activity can reduce the risk of cardiovascular disease, and people at risk are advised to engage in 150 minutes of moderate or 75 minutes of vigorous intensity aerobic exercise a week. Keeping a healthy weight, drinking alcohol within the recommended limits, and quitting smoking reduce the risk of cardiovascular disease.
Substituting polyunsaturated fats such as olive oil and rapeseed oil instead of saturated fats may reduce the risk of myocardial infarction, although there is not universal agreement. Dietary modifications are recommended by some national authorities, with recommendations including increasing the intake of wholegrain starch, reducing sugar intake (particularly of refined sugar), consuming five portions of fruit and vegetables daily, consuming two or more portions of fish per week, and consuming 4–5 portions of unsalted nuts, seeds, or legumes per week. The dietary pattern with the greatest support is the Mediterranean diet.Vitamins and mineral supplements are of no proven benefit, and neither are plant stanols or sterols.
Public health measures may also act at a population level to reduce the risk of myocardial infarction, for example by reduce unhealthy diets (excessive salt, saturated fat and trans fat) including food labeling and marketing requirements as well as requirements for catering and restaurants, and stimulating physical activity. This may be part of regional cardiovascular disease prevention programs, or through the health impact assessment of regional and local plans and policies.
Most guidelines recommend combining different preventive strategies. A 2015 Cochrane Review found some evidence that such an approach might help with blood pressure, body mass index and waist circumference. However, there was insufficient evidence to show an effect on mortality or actual cardio-vascular events.
Statins, drugs that act to lower blood cholesterol, decrease the incidence and mortality rates of myocardial infarctions. They are often recommended in those at an elevated risk of cardiovascular diseases.
Aspirin has been studied extensively in people considered at increased risk of myocardial infarction. Based on numerous studies in different groups (e.g. people with or without diabetes), there does not appear to be a benefit strong enough to outweigh the risk of excessive bleeding. Nevertheless, many clinical practice guidelines continue to recommend aspirin for primary prevention, and some researchers feel that those with very high cardiovascular risk but low risk of bleeding should continue to receive aspirin.
There is a large crossover between the lifestyle and activity recommendations to prevent a myocardial infarction, and those that may be adopted as secondary prevention after an initial myocardial infarct. Recommendations include stopping smoking, a gradual return to exercise, eating a healthy diet, low in saturated fat and low in cholesterol, and drinking alcohol within recommended limits, exercising, and trying to achieve a healthy weight. Exercise is both safe and effective even if people have had stents or heart failure, and is recommended to start gradually after 1–2 weeks. Counselling should be provided relating to medications used, and for warning signs of depression. Previous studies suggested a benefit from omega-3 fatty acid supplementation but this has not been confirmed.
Following a heart attack, nitrates, when taken for two days, and ACE-inhibitors decrease the risk of death. Other medications include:
Aspirin is continued indefinitely, as well as another antiplatelet agent such as clopidogrel or ticagrelor ("dual antiplatelet therapy" or DAPT) for up to twelve months. If someone has another medical condition that requires anticoagulation (e.g. with warfarin) this may need to be adjusted based on risk of further cardiac events as well as bleeding risk. In those who have had a stent, more than 12 months of clopidogrel plus aspirin does not affect the risk of death.
Beta blocker therapy such as metoprolol or carvedilol is recommended to be started within 24 hours, provided there is no acute heart failure or heart block. The dose should be increased to the highest tolerated. Contrary to what was long believed, the use of beta blockers does not appear to affect the risk of death, possibly because other treatments for MI have improved. When beta blocker medication is given within the first 24–72 hours of a STEMI no lives are saved. However, 1 in 200 people were prevented from a repeat heart attack, and another 1 in 200 from having an abnormal heart rhythm. Additionally, for 1 in 91 the medication causes a temporary decrease in the heart's ability to pump blood.
Statin therapy has been shown to reduce mortality and subsequent cardiac events, and should be commenced with the aim of lowering LDL cholesterol. Other medications, such as ezetimibe, may also be added with this goal in mind.
A defibrillator, an electric device connected to the heart and surgically inserted under the skin, may be recommended. This is particularly if there are any ongoing signs of heart failure, with a low left ventricular ejection fraction and a New York Heart Association grade II or III after 40 days of the infarction. Defibrillators detect potentially fatal arrhythmia and deliver an electrical shock to the person to depolarize a critical mass of the heart muscle.
The prognosis after myocardial infarction varies greatly depending on the extent and location of the affected heart muscle, and the development and management of complications. Prognosis is worse with older age, and social isolation. Anterior infarcts, persistent ventricular tachycardia or fibrillation, development of heart blocks, and left ventricular impairment are all associated with poorer prognosis. Without treatment, about a quarter of those affected by MI die within minutes, and about forty percent within the first month. Morbidity and mortality from myocardial infarction has however improved over the years due to earlier and better treatment: in those who have an STEMI in the United States, between 5 and 6 percent die before leaving the hospital and 7 to 18 percent die within a year.
Complications may occur immediately following the myocardial infarction or may take time to develop. Disturbances of heart rhythms, including atrial fibrillation, ventricular tachycardia and fibrillation and heart block can arise as a result of ischemia, cardiac scarring, and infarct location.Stroke is also a risk, either as a result of clots transmitted from the heart during PCI, as a result of bleeding following anticoagulation, or as a result of disturbances in the heart's ability to pump effectively as a result of the infarction.Regurgitation of blood through the mitral valve is possible, particularly if the infarction causes dysfunction of the papillary muscle.Cardiogenic shock as a result of the heart being unable to adequately pump blood may develop, dependent on infarct size, and is most likely to occur within the days following an acute myocardial infarction. Cardiogenic shock is the largest cause of in-hospital mortality. Rupture of the ventricular dividing wall or left ventricular wall may occur within the initial weeks.Dressler's syndrome, a reaction following larger infarcts and a cause of pericarditis is also possible.
Heart failure may develop as a long-term consequence, with an impaired ability of heart muscle to pump, scarring, and increase in size of the existing muscle. Aneurysm of the left ventricle myocardium develops in about 10% of MI and is itself a risk factor for heart failure, ventricular arrhythmia and the development of clots.
Rates of death from ischemic heart disease (IHD) have slowed or declined in most high-income countries, although cardiovascular disease still accounted for one in three of all deaths in the USA in 2008. For example, rates of death from cardiovascular disease have decreased almost a third between 2001 and 2011 in the United States.
In contrast, IHD is becoming a more common cause of death in the developing world. For example, in India, IHD had become the leading cause of death by 2004, accounting for 1.46 million deaths (14% of total deaths) and deaths due to IHD were expected to double during 1985–2015. Globally, disability adjusted life years (DALYs) lost to ischemic heart disease are predicted to account for 5.5% of total DALYs in 2030, making it the second-most-important cause of disability (after unipolar depressive disorder), as well as the leading cause of death by this date.
Society and culture
Depictions of heart attacks in popular media often include collapsing or loss of consciousness which are not common symptoms; these depictions contribute to widespread misunderstanding about the symptoms of myocardial infarctions, which in turn contributes to people not getting care when they should.
At common law, in general, a myocardial infarction is a disease, but may sometimes be an injury. This can create coverage issues in the administration of no-fault insurance schemes such as workers' compensation. In general, a heart attack is not covered; however, it may be a work-related injury if it results, for example, from unusual emotional stress or unusual exertion. In addition, in some jurisdictions, heart attacks suffered by persons in particular occupations such as police officers may be classified as line-of-duty injuries by statute or policy. In some countries or states, a person having suffered from an MI may be prevented from participating in activity that puts other people's lives at risk, for example driving a car or flying an airplane.
^ abcdefghiSteg PG, James SK, Atar D, Badano LP, Blömstrom-Lundqvist C, Borger MA, Di Mario C, Dickstein K, Ducrocq G, Fernandez-Aviles F, Gershlick AH, Giannuzzi P, Halvorsen S, Huber K, Juni P, Kastrati A, Knuuti J, Lenzen MJ, Mahaffey KW, Valgimigli M, van 't Hof A, Widimsky P, Zahger D (October 2012). "ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation". European Heart Journal. 33 (20): 2569–619. doi:10.1093/eurheartj/ehs215. PMID22922416.
^ abcdefO'Connor RE, Brady W, Brooks SC, Diercks D, Egan J, Ghaemmaghami C, Menon V, O'Neil BJ, Travers AH, Yannopoulos D (November 2010). "Part 10: acute coronary syndromes: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care". Circulation. 122 (18 Suppl 3): S787–817. doi:10.1161/CIRCULATIONAHA.110.971028. PMID20956226.
^Coventry LL, Finn J, Bremner AP (2011). "Sex differences in symptom presentation in acute myocardial infarction: a systematic review and meta-analysis". Heart & Lung. 40 (6): 477–91. doi:10.1016/j.hrtlng.2011.05.001. PMID22000678.
^ abcdValensi P, Lorgis L, Cottin Y (March 2011). "Prevalence, incidence, predictive factors and prognosis of silent myocardial infarction: a review of the literature". Archives of Cardiovascular Diseases. 104 (3): 178–88. doi:10.1016/j.acvd.2010.11.013. PMID21497307.
^ abcdefghijklmnoBritton, the editors Nicki R. Colledge, Brian R. Walker, Stuart H. Ralston ; illustrated by Robert (2010). Davidson's principles and practice of medicine (21st ed.). Edinburgh: Churchill Livingstone/Elsevier. pp. 588–599. ISBN978-0-7020-3085-7.
^Hamm CW, Bassand JP, Agewall S, Bax J, Boersma E, Bueno H, Caso P, Dudek D, Gielen S, Huber K, Ohman M, Petrie MC, Sonntag F, Uva MS, Storey RF, Wijns W, Zahger D (December 2011). "ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC)". European Heart Journal. 32 (23): 2999–3054. doi:10.1093/eurheartj/ehr236. PMID21873419.
^ abcdefghijklO'Gara PT, Kushner FG, Ascheim DD, Casey DE, Chung MK, de Lemos JA, Ettinger SM, Fang JC, Fesmire FM, Franklin BA, Granger CB, Krumholz HM, Linderbaum JA, Morrow DA, Newby LK, Ornato JP, Ou N, Radford MJ, Tamis-Holland JE, Tommaso CL, Tracy CM, Woo YJ, Zhao DX, Anderson JL, Jacobs AK, Halperin JL, Albert NM, Brindis RG, Creager MA, DeMets D, Guyton RA, Hochman JS, Kovacs RJ, Kushner FG, Ohman EM, Stevenson WG, Yancy CW (January 2013). "2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines". Circulation. 127 (4): e362–425. doi:10.1161/CIR.0b013e3182742cf6. PMID23247304.
^ abcdefghijklmnopqrThygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, Katus HA, Lindahl B, Morrow DA, Clemmensen PM, Johanson P, Hod H, Underwood R, Bax JJ, Bonow RO, Pinto F, Gibbons RJ, Fox KA, Atar D, Newby LK, Galvani M, Hamm CW, Uretsky BF, Steg PG, Wijns W, Bassand JP, Menasché P, Ravkilde J, Ohman EM, Antman EM, Wallentin LC, Armstrong PW, Simoons ML, Januzzi JL, Nieminen MS, Gheorghiade M, Filippatos G, Luepker RV, Fortmann SP, Rosamond WD, Levy D, Wood D, Smith SC, Hu D, Lopez-Sendon JL, Robertson RM, Weaver D, Tendera M, Bove AA, Parkhomenko AN, Vasilieva EJ, Mendis S (October 2012). "Third universal definition of myocardial infarction". Circulation. 126 (16): 2020–35. doi:10.1161/CIR.0b013e31826e1058. PMID22923432.
^ abcdVan de Werf F, Bax J, Betriu A, Blomstrom-Lundqvist C, Crea F, Falk V, Filippatos G, Fox K, Huber K, Kastrati A, Rosengren A, Steg PG, Tubaro M, Verheugt F, Weidinger F, Weis M (December 2008). "Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation: the Task Force on the Management of ST-Segment Elevation Acute Myocardial Infarction of the European Society of Cardiology". European Heart Journal. 29 (23): 2909–45. doi:10.1093/eurheartj/ehn416. PMID19004841.
^ abcdKasper, Dennis L.; Fauci, Anthony S.,; Hauser, Stephen L.; Longo, Dan L.; Jameson, J. Larry; Loscalzo, Joseph (2015). Harrison's Principles of Internal Medicine. McGraw Hill Education. pp. 98–99. ISBN978-0-07-180215-4. OCLC923181481.
^Canto JG, Goldberg RJ, Hand MM, Bonow RO, Sopko G, Pepine CJ, Long T (December 2007). "Symptom presentation of women with acute coronary syndromes: myth vs reality". Archives of Internal Medicine. 167 (22): 2405–13. doi:10.1001/archinte.167.22.2405. PMID18071161.
^Ashton, Rendell; Raman, Dileep. "Dyspnea". www.clevelandclinicmeded.com. Cleveland Clinic. Archived from the original on 11 July 2017. Retrieved 24 May 2017.
^Davis TM, Fortun P, Mulder J, Davis WA, Bruce DG (March 2004). "Silent myocardial infarction and its prognosis in a community-based cohort of Type 2 diabetic patients: the Fremantle Diabetes Study". Diabetologia. 47 (3): 395–399. doi:10.1007/s00125-004-1344-4. PMID14963648.
^Rubin, Emanuel; Gorstein, Fred; Rubin, Raphael; Schwarting, Roland; Strayer, David (2001). Rubin's Pathology — Clinicopathological Foundations of Medicine. Maryland: Lippincott Williams & Wilkins. p. 549. ISBN978-0-7817-4733-2.
^ abcPerk J, De Backer G, Gohlke H, Graham I, Reiner Z, Verschuren M, Albus C, Benlian P, Boysen G, Cifkova R, Deaton C, Ebrahim S, Fisher M, Germano G, Hobbs R, Hoes A, Karadeniz S, Mezzani A, Prescott E, Ryden L, Scherer M, Syvänne M, Scholte op Reimer WJ, Vrints C, Wood D, Zamorano JL, Zannad F (July 2012). "European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts)". European Heart Journal. 33 (13): 1635–701. doi:10.1093/eurheartj/ehs092. PMID22555213.
^Smith SC, Allen J, Blair SN, Bonow RO, Brass LM, Fonarow GC, Grundy SM, Hiratzka L, Jones D, Krumholz HM, Mosca L, Pearson T, Pfeffer MA, Taubert KA (May 2006). "AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update endorsed by the National Heart, Lung, and Blood Institute". Journal of the American College of Cardiology. 47 (10): 2130–9. doi:10.1016/j.jacc.2006.04.026. PMID16697342.
^ abHooper L, Martin N, Abdelhamid A, Davey Smith G (June 2015). "Reduction in saturated fat intake for cardiovascular disease". The Cochrane Database of Systematic Reviews. 6 (6): CD011737. doi:10.1002/14651858.CD011737. PMID26068959.
^ abcChowdhury R, Warnakula S, Kunutsor S, Crowe F, Ward HA, Johnson L, Franco OH, Butterworth AS, Forouhi NG, Thompson SG, Khaw KT, Mozaffarian D, Danesh J, Di Angelantonio E (March 2014). "Association of dietary, circulating, and supplement fatty acids with coronary risk: a systematic review and meta-analysis". Annals of Internal Medicine. 160 (6): 398–406. doi:10.7326/M13-1788. PMID24723079.
^Roach RE, Helmerhorst FM, Lijfering WM, Stijnen T, Algra A, Dekkers OM (August 2015). "Combined oral contraceptives: the risk of myocardial infarction and ischemic stroke". The Cochrane Database of Systematic Reviews (8): CD011054. doi:10.1002/14651858.CD011054.pub2. PMID26310586.
^Mustafic H, Jabre P, Caussin C, Murad MH, Escolano S, Tafflet M, Périer MC, Marijon E, Vernerey D, Empana JP, Jouven X (February 2012). "Main air pollutants and myocardial infarction: a systematic review and meta-analysis". JAMA. 307 (7): 713–21. doi:10.1001/jama.2012.126. PMID22337682.
^ abChatzidimitriou D, Kirmizis D, Gavriilaki E, Chatzidimitriou M, Malisiovas N (October 2012). "Atherosclerosis and infection: is the jury still not in?". Future Microbiology. 7 (10): 1217–30. doi:10.2217/fmb.12.87. PMID23030426.
^Hulten EA, Carbonaro S, Petrillo SP, Mitchell JD, Villines TC (March 2011). "Prognostic value of cardiac computed tomography angiography: a systematic review and meta-analysis". Journal of the American College of Cardiology. 57 (10): 1237–47. doi:10.1016/j.jacc.2010.10.011. PMID21145688.
^Clarke R, Halsey J, Bennett D, Lewington S (February 2011). "Homocysteine and vascular disease: review of published results of the homocysteine-lowering trials". Journal of Inherited Metabolic Disease. 34 (1): 83–91. doi:10.1007/s10545-010-9235-y. PMID21069462.
^Lonn E (September 2007). "Homocysteine in the prevention of ischemic heart disease, stroke and venous thromboembolism: therapeutic target or just another distraction?". Current Opinion in Hematology. 14 (5): 481–7. doi:10.1097/MOH.0b013e3282c48bd8. PMID17934354.
^ abcdefBritton, the editors Nicki R. Colledge, Brian R. Walker, Stuart H. Ralston ; illustrated by Robert (2010). Davidson's principles and practice of medicine (21st ed.). Edinburgh: Churchill Livingstone/Elsevier. pp. 577–9. ISBN978-0-7020-3085-7.
^Pickering JW, Than MP, Cullen L, Aldous S, Ter Avest E, Body R, Carlton EW, Collinson P, Dupuy AM, Ekelund U, Eggers KM, Florkowski CM, Freund Y, George P, Goodacre S, Greenslade JH, Jaffe AS, Lord SJ, Mokhtari A, Mueller C, Munro A, Mustapha S, Parsonage W, Peacock WF, Pemberton C, Richards AM, Sanchis J, Staub LP, Troughton R, Twerenbold R, Wildi K, Young J (May 2017). "Rapid Rule-out of Acute Myocardial Infarction With a Single High-Sensitivity Cardiac Troponin T Measurement Below the Limit of Detection: A Collaborative Meta-analysis". Annals of Internal Medicine. 166 (10): 715–724. doi:10.7326/M16-2562. PMID28418520.
^ abcdAmsterdam EA, Wenger NK, Brindis RG, Casey DE, Ganiats TG, Holmes DR, Jaffe AS, Jneid H, Kelly RF, Kontos MC, Levine GN, Liebson PR, Mukherjee D, Peterson ED, Sabatine MS, Smalling RW, Zieman SJ (December 2014). "2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines". Circulation. 130 (25): e344–426. doi:10.1161/CIR.0000000000000134. PMID25249585.
^Lipinski MJ, Escárcega RO, D'Ascenzo F, Magalhães MA, Baker NC, Torguson R, Chen F, Epstein SE, Miró O, Llorens P, Giannitsis E, Lotze U, Lefebvre S, Sebbane M, Cristol JP, Chenevier-Gobeaux C, Meune C, Eggers KM, Charpentier S, Twerenbold R, Mueller C, Biondi-Zoccai G, Waksman R (May 2014). "A systematic review and collaborative meta-analysis to determine the incremental value of copeptin for rapid rule-out of acute myocardial infarction". The American Journal of Cardiology. 113 (9): 1581–91. doi:10.1016/j.amjcard.2014.01.436. PMID24731654.
^ abcBritton, the editors Nicki R. Colledge, Brian R. Walker, Stuart H. Ralston ; illustrated by Robert (2010). Davidson's principles and practice of medicine (21st ed.). Edinburgh: Churchill Livingstone/Elsevier. pp. 529–30. ISBN978-0-7020-3085-7.
^Kasper, Dennis L.; Fauci, Anthony S.,; Hauser, Stephen L.; Longo, Dan L.; Jameson, J. Larry; Loscalzo, Joseph (2015). Harrison's principles of internal medicine. McGraw Hill Education. p. 1457. ISBN978-0-07-180215-4. OCLC923181481.
^ abcBritton, the editors Nicki R. Colledge, Brian R. Walker, Stuart H. Ralston ; illustrated by Robert (2010). Davidson's principles and practice of medicine (21st ed.). Edinburgh: Churchill Livingstone/Elsevier. pp. 535, 539. ISBN978-0-7020-3085-7.
^Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, Katus HA, Lindahl B, Morrow DA, Clemmensen PM, Johanson P, Hod H, Underwood R, Bax JJ, Bonow RO, Pinto F, Gibbons RJ, Fox KA, Atar D, Newby LK, Galvani M, Hamm CW, Uretsky BF, Steg PG, Wijns W, Bassand JP, Menasché P, Ravkilde J, Ohman EM, Antman EM, Wallentin LC, Armstrong PW, Simoons ML, Januzzi JL, Nieminen MS, Gheorghiade M, Filippatos G, Luepker RV, Fortmann SP, Rosamond WD, Levy D, Wood D, Smith SC, Hu D, Lopez-Sendon JL, Robertson RM, Weaver D, Tendera M, Bove AA, Parkhomenko AN, Vasilieva EJ, Mendis S (October 2012). "Third universal definition of myocardial infarction". Circulation. 126 (16): 2020–35. doi:10.1161/CIR.0b013e31826e1058. PMID22923432.
^ abAndrade-Castellanos CA, Colunga-Lozano LE, Delgado-Figueroa N, Magee K (June 2014). "Heparin versus placebo for non-ST elevation acute coronary syndromes". The Cochrane Database of Systematic Reviews. 6 (6): CD003462. doi:10.1002/14651858.CD003462.pub3. PMID24972265.
^Neumar RW, Shuster M, Callaway CW, Gent LM, Atkins DL, Bhanji F, Brooks SC, de Caen AR, Donnino MW, Ferrer JM, Kleinman ME, Kronick SL, Lavonas EJ, Link MS, Mancini ME, Morrison LJ, O'Connor RE, Samson RA, Schexnayder SM, Singletary EM, Sinz EH, Travers AH, Wyckoff MH, Hazinski MF (November 2015). "Part 1: Executive Summary: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care". Circulation. 132 (18 Suppl 2): S315–67. doi:10.1161/cir.0000000000000252. PMID26472989.
^McCaul M, Lourens A, Kredo T (September 2014). "Pre-hospital versus in-hospital thrombolysis for ST-elevation myocardial infarction". The Cochrane Database of Systematic Reviews. 9 (9): CD010191. doi:10.1002/14651858.CD010191.pub2. PMID25208209.
^Cabello JB, Burls A, Emparanza JI, Bayliss SE, Quinn T (December 2016). "Oxygen therapy for acute myocardial infarction". The Cochrane Database of Systematic Reviews. 12: CD007160. doi:10.1002/14651858.CD007160.pub4. PMID27991651.
^Hofmann R, James SK, Jernberg T, Lindahl B, Erlinge D, Witt N, Arefalk G, Frick M, Alfredsson J, Nilsson L, Ravn-Fischer A, Omerovic E, Kellerth T, Sparv D, Ekelund U, Linder R, Ekström M, Lauermann J, Haaga U, Pernow J, Östlund O, Herlitz J, Svensson L (September 2017). "Oxygen Therapy in Suspected Acute Myocardial Infarction". The New England Journal of Medicine. 377 (13): 1240–1249. doi:10.1056/nejmoa1706222. PMID28844200.
^Abuzaid A, Fabrizio C, Felpel K, Al Ashry HS, Ranjan P, Elbadawi A, Mohamed AH, Barssoum K, Elgendy IY (March 2018). "Oxygen Therapy in Patients with Acute Myocardial Infarction: A Systemic Review and Meta-Analysis". The American Journal of Medicine. 131 (6): 693–701. doi:10.1016/j.amjmed.2017.12.027. PMID29355510.
^Sepehrvand, N; James, SK; Stub, D; Khoshnood, A; Ezekowitz, JA; Hofmann, R (29 March 2018). "Effects of supplemental oxygen therapy in patients with suspected acute myocardial infarction: a meta-analysis of randomised clinical trials". Heart. 104 (20): heartjnl–2018–313089. doi:10.1136/heartjnl-2018-313089. PMID29599378.
^Stradling C, Hamid M, Taheri S, Thomas GN (2014). "A review of dietary influences on cardiovascular health: part 2: dietary patterns". Cardiovascular & Hematological Disorders Drug Targets. 14 (1): 50–63. doi:10.2174/1871529x14666140701095426. PMID24993125.
^Fortmann SP, Burda BU, Senger CA, Lin JS, Whitlock EP (December 2013). "Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: An updated systematic evidence review for the U.S. Preventive Services Task Force". Annals of Internal Medicine. 159 (12): 824–34. doi:10.7326/0003-4819-159-12-201312170-00729. PMID24217421.
^Ebrahim, Shah; Taylor, Fiona; Ward, Kirsten; Beswick, Andrew; Burke, Margaret; Davey Smith, George (2011-01-19). "Cochrane Database of Systematic Reviews". Cochrane Database of Systematic Reviews (1): CD001561. doi:10.1002/14651858.cd001561.pub3. PMID21249647.
^Taylor F, Huffman MD, Macedo AF, Moore TH, Burke M, Davey Smith G, Ward K, Ebrahim S (January 2013). "Statins for the primary prevention of cardiovascular disease". The Cochrane Database of Systematic Reviews. 1 (1): CD004816. doi:10.1002/14651858.CD004816.pub5. PMID23440795.
^Matthys F, De Backer T, De Backer G, Stichele RV (March 2014). "Review of guidelines on primary prevention of cardiovascular disease with aspirin: how much evidence is needed to turn a tanker?". European Journal of Preventive Cardiology. 21 (3): 354–65. doi:10.1177/2047487312472077. PMID23610452.
^Perez MI, Musini VM, Wright JM (October 2009). "Effect of early treatment with anti-hypertensive drugs on short and long-term mortality in patients with an acute cardiovascular event". The Cochrane Database of Systematic Reviews (4): CD006743. doi:10.1002/14651858.CD006743.pub2. PMID19821384.
^Hazinski MF, Nolan JP, Aickin R, Bhanji F, Billi JE, Callaway CW, Castren M, de Caen AR, Ferrer JM, Finn JC, Gent LM, Griffin RE, Iverson S, Lang E, Lim SH, Maconochie IK, Montgomery WH, Morley PT, Nadkarni VM, Neumar RW, Nikolaou NI, Perkins GD, Perlman JM, Singletary EM, Soar J, Travers AH, Welsford M, Wyllie J, Zideman DA (October 2015). "Part 1: Executive Summary: 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations". Circulation (Review). 132 (16 Suppl 1): S2–39. doi:10.1161/CIR.0000000000000270. PMID26472854.
^López de Sá E, López-Sendón J, Anguera I, Bethencourt A, Bosch X (November 2002). "Prognostic value of clinical variables at presentation in patients with non-ST-segment elevation acute coronary syndromes: results of the Proyecto de Estudio del Pronóstico de la Angina (PEPA)". Medicine. 81 (6): 434–42. doi:10.1097/00005792-200211000-00004. PMID12441900.
^Weir RA, McMurray JJ, Velazquez EJ (May 2006). "Epidemiology of heart failure and left ventricular systolic dysfunction after acute myocardial infarction: prevalence, clinical characteristics, and prognostic importance". The American Journal of Cardiology. 97 (10A): 13F–25F. doi:10.1016/j.amjcard.2006.03.005. PMID16698331.
^ abcWorld Health Organization (2008). The Global Burden of Disease: 2004 Update. Geneva: World Health Organization. ISBN978-92-4-156371-0.
^American Heart Association Statistics Committee and Stroke Statistics, Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, et al. (January 2012). "Executive summary: heart disease and stroke statistics--2012 update: a report from the American Heart Association". Circulation. 125 (1): 188–97. doi:10.1161/CIR.0b013e3182456d46. PMID22215894.
^Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. (January 2015). "Heart disease and stroke statistics--2015 update: a report from the American Heart Association". Circulation. 131 (4): e29–322. doi:10.1161/cir.0000000000000152. PMID25520374. From 2001 to 2011, death rates attributable to CVD declined 30.8%.
^Gupta R, Joshi P, Mohan V, Reddy KS, Yusuf S (January 2008). "Epidemiology and causation of coronary heart disease and stroke in India". Heart. 94 (1): 16–26. doi:10.1136/hrt.2007.132951. PMID18083949.
Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, et al. (March 2016). "2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention and the 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Society for Cardiovascular Angiography and Interventions". Circulation. 133 (11): 1135–47. doi:10.1161/CIR.0000000000000336. PMID26490017.