Myocardial infarction
A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops in one of the arteries of the heart, causing infarction (tissue death) to the heart muscle.[1] The most common symptom is retrosternal chest pain or discomfort that classically radiates to the left shoulder, arm, or jaw.[1] The pain may occasionally feel like heartburn.[1] This is the dangerous type of acute coronary syndrome.
Other symptoms may include shortness of breath, nausea, feeling faint, a cold sweat, feeling tired, and decreased level of consciousness.[1] Women more often present without chest pain and instead have neck pain, arm pain or feel tired.[11] Among those over 70-75 years old, about 5% have had an MI with little or no history of symptoms.[12] An MI may cause heart failure, an irregular heartbeat, cardiogenic shock or cardiac arrest.[3][4]
Most MIs occur due to coronary artery disease.[3] Risk factors include high blood pressure, smoking, diabetes, lack of exercise, obesity, high blood cholesterol, poor diet, and excessive alcohol intake.[5][6] The complete blockage of a coronary artery caused by a rupture of an atherosclerotic plaque is usually the underlying mechanism of an MI.[3] MIs are less commonly caused by coronary artery spasms, which may be due to cocaine, significant emotional stress (often known as Takotsubo syndrome or broken heart syndrome) and extreme cold, among others.[13][14] Many tests are helpful with diagnosis, including electrocardiograms (ECGs), blood tests and coronary angiography.[7] An ECG, which is a recording of the heart's electrical activity, may confirm an ST elevation MI (STEMI), if ST elevation is present.[8][15] Commonly used blood tests include troponin and less often creatine kinase MB.[7]
Treatment of an MI is time-critical.[16] Aspirin is an appropriate immediate treatment for a suspected MI.[9] Nitroglycerin or opioids may be used to help with chest pain; however, they do not improve overall outcomes.[8][9] Supplemental oxygen is recommended in those with low oxygen levels or shortness of breath.[9] 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.[8] 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.[9] In people with blockages of multiple coronary arteries and diabetes, coronary artery bypass surgery (CABG) may be recommended rather than angioplasty.[17] After an MI, lifestyle modifications, along with long-term treatment with aspirin, beta blockers and statins, are typically recommended.[8]
Worldwide, about 15.9 million myocardial infarctions occurred in 2015.[10] More than 3 million people had an ST elevation MI, and more than 4 million had an NSTEMI.[18] STEMIs occur about twice as often in men as women.[19] About one million people have an MI each year in the United States.[3] In the developed world, the risk of death in those who have had a STEMI is about 10%.[8] Rates of MI for a given age have decreased globally between 1990 and 2010.[20] In 2011, an 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.[21]
Terminology
Myocardial infarction (MI) refers to tissue death (infarction) of a part of the heart muscle (myocardium), caused by ischemia, the lack of oxygen delivery to myocardial tissue. 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.[22] Unlike the other type of acute coronary syndrome, unstable angina, a myocardial infarction occurs when there is cell death, which can be estimated by a blood test that measures biomarkers (the cardiac protein troponin).[23] 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.[24]
The phrase "heart attack" is often used non-specifically to refer to myocardial infarction. 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 leading to death.[25] 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.[26]
Signs and symptoms
Chest pain that may or may not radiate to other parts of the body is the most typical and significant symptom of myocardial infarction. It might be accompanied by other symptoms such as sweating.[27]
Pain
Chest pain is one of the most common symptoms 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.[28][29] The pain most suggestive of an acute MI, with the highest likelihood ratio, is pain radiating to the right arm and shoulder.[30][29] Similarly, chest pain similar to a previous heart attack is also suggestive.[31] The pain associated with MI is usually diffuse, does not change with position, and lasts for more than 20 minutes.[24] The pain may be described as pressure, tightness, a knife-like sensation, tearing, or burning.[29] In some individuals it may manifest as a sense of impending doom rather than typical pain, or pain may be absent entirely.[29] 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.[32]
Typically, chest pain because of ischemia, be it unstable angina or myocardial infarction, lessens with the use of nitroglycerin, but nitroglycerin may also relieve chest pain arising from non-cardiac causes.[33]
Other
Chest pain may be accompanied by sweating, nausea or vomiting, and fainting,[24][30] and these symptoms may also occur without any pain at all.[28] Dizziness or lightheadedness is common and occurs due to reduction in oxygen and blood to the brain. In females, the most common symptoms of myocardial infarction include shortness of breath, weakness, and fatigue.[34] Females are more likely to have unusual or unexplained tiredness and nausea or vomiting as symptoms.[35] Females having heart attacks are more likely to have palpitations, back pain, labored breath, vomiting, and left arm pain than males, although the studies showing these differences had high variability.[36] Females are less likely to report chest pain during a heart attack and more likely to report nausea, jaw pain, neck pain, cough, and fatigue, although these findings are inconsistent across studies.[37] Females with heart attacks also had more indigestion, dizziness, loss of appetite, and loss of consciousness.[38] Shortness of breath is a common, and sometimes the only symptom, occurring when damage to the heart limits the output of the left ventricle, with breathlessness arising either from low oxygen in the blood or pulmonary edema.[28][39]
Other less common symptoms include weakness, light-headedness, palpitations, and abnormalities in heart rate or blood pressure.[16] These symptoms are likely induced by a massive surge of catecholamines from the sympathetic nervous system, which occurs in response to pain and, where present, low blood pressure.[40] Loss of consciousness can occur in myocardial infarctions due to inadequate blood flow to the brain and cardiogenic shock, and sudden death, frequently due to the development of ventricular fibrillation.[41] When the brain was without oxygen for too long due to a myocardial infarction, coma and persistent vegetative state can occur. Cardiac arrest, and atypical symptoms such as palpitations, occur more frequently in females, the elderly, those with diabetes, in people who have just had surgery, and in critically ill patients.[24]
Absence
"Silent" myocardial infarctions can happen without any symptoms at all.[12] These cases can be discovered later on electrocardiograms, using blood enzyme tests, or at autopsy after a person has died. Such silent myocardial infarctions represent between 22 and 64% of all infarctions,[12] and are more common in the elderly,[12] in those with diabetes mellitus[16] and after heart transplantation. In people with diabetes, differences in pain threshold, autonomic neuropathy, and psychological factors have been cited as possible explanations for the lack of symptoms.[42] In heart transplantation, the donor heart is not fully innervated by the nervous system of the recipient.[43]
Risk factors
The most prominent risk factors for myocardial infarction are older age, actively smoking, high blood pressure, diabetes mellitus, and total cholesterol and high-density lipoprotein levels.[44] Many risk factors of myocardial infarction are shared with coronary artery disease, the primary cause of myocardial infarction,[16] with other risk factors including male sex, low levels of physical activity, a past family history, obesity, and alcohol use.[16] Risk factors for myocardial disease are often included in risk factor stratification scores, such as the Framingham Risk Score.[19] At any given age, men are more at risk than women for the development of cardiovascular disease.[45] High levels of blood cholesterol is a known risk factor, particularly high low-density lipoprotein, low high-density lipoprotein, and high triglycerides.[46]
Many risk factors for myocardial infarction are potentially modifiable, with the most important being tobacco smoking (including secondhand smoke).[16] Smoking appears to be the cause of about 36% and obesity the cause of 20% of coronary artery disease.[47] Lack of physical activity has been linked to 7–12% of cases.[47][48] Less common causes include stress-related causes such as job stress, which accounts for about 3% of cases,[47] and chronic high stress levels.[49]
Diet
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,[50] while other studies find little evidence that reducing dietary saturated fat or increasing polyunsaturated fat intake affects heart attack risk.[51][52] Dietary cholesterol does not appear to have a significant effect on blood cholesterol and thus recommendations about its consumption may not be needed.[53] Trans fats do appear to increase risk.[51] Acute and prolonged intake of high quantities of alcoholic drinks (3–4 or more daily) increases the risk of a heart attack.[54]
Genetics
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.[45]
Genome-wide association studies have found 27 genetic variants that are associated with an increased risk of myocardial infarction.[55] The strongest association of MI has been found with chromosome 9 on the short arm p at locus 21, which contains genes CDKN2A and 2B, although the single nucleotide polymorphisms that are implicated are within a non-coding region.[55] The majority of these variants are in regions that have not been previously implicated in coronary artery disease. The following genes have an association with MI: PCSK9, SORT1, MIA3, WDR12, MRAS, PHACTR1, LPA, TCF21, MTHFDSL, ZC3HC1, CDKN2A, 2B, ABO, PDGF0, APOA5, MNF1ASM283, COL4A1, HHIPC1, SMAD3, ADAMTS7, RAS1, SMG6, SNF8, LDLR, SLC5A3, MRPS6, KCNE2.[55]
Other
The risk of having a myocardial infarction increases with older age, low physical activity, and low socioeconomic status.[45] Heart attacks appear to occur more commonly in the morning hours, especially between 6 am and noon.[56] Evidence suggests that heart attacks are at least three times more likely to occur in the morning than in the late evening.[57] Shift work is also associated with a higher risk of MI.[58] One analysis has found an increase in heart attacks immediately following the start of daylight saving time.[59]
Women who use combined oral contraceptive pills have a modestly increased risk of myocardial infarction, especially in the presence of other risk factors.[60] The use of non-steroidal anti-inflammatory drugs (NSAIDs), even for as short as a week, increases risk.[61]
Endometriosis in women under the age of 40 is an identified risk factor.[62]
Air pollution is also an important modifiable risk. Short-term exposure to air pollution such as carbon monoxide, nitrogen dioxide, and sulfur dioxide (but not ozone) has been associated with MI and other acute cardiovascular events.[63] For sudden cardiac deaths, every increment of 30 units in Pollutant Standards Index correlated with an 8% increased risk of out-of-hospital cardiac arrest on the day of exposure.[64] Extremes of temperature are also associated.[65]
A number of acute and chronic infections including Chlamydophila pneumoniae, influenza, Helicobacter pylori, and Porphyromonas gingivalis among others have been linked to atherosclerosis and myocardial infarction.[66] Myocardial infarction can also occur as a late consequence of Kawasaki disease.[67]
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.[68] High blood levels of the amino acid homocysteine is associated with premature atherosclerosis;[69] whether elevated homocysteine in the normal range is causal is controversial.[70]
In people without evident coronary artery disease, possible causes for the myocardial infarction are coronary spasm or coronary artery dissection.[71]
Mechanism
Atherosclerosis
The most common cause of a myocardial infarction is the rupture of an atherosclerotic plaque on an artery supplying heart muscle.[41][72] 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.[73] Atherosclerotic plaques are often present for decades before they result in symptoms.[73]
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.[74] Atherosclerosis is characterized by progressive inflammation of the walls of the arteries.[73] 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).[73] The cholesterol crystals have been associated with plaque rupture through mechanical injury and inflammation.[75]
Other causes
Atherosclerotic disease is not the only cause of myocardial infarction, but it may exacerbate or contribute to other causes. A myocardial infarction may result from a heart with a limited blood supply subject to increased oxygen demands, such as in fever, a fast heart rate, hyperthyroidism, too few red blood cells in the bloodstream, or low blood pressure. Damage or failure of procedures such as percutaneous coronary intervention (PCI) or coronary artery bypass grafts (CABG) may cause a myocardial infarction. Spasm of coronary arteries, such as Prinzmetal's angina may cause blockage.[24][28]
Tissue death
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 collagen scar forms in their place.[73] 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.[76]
Cells in the area with the worst blood supply, just below the inner surface of the heart (endocardium), are most susceptible to damage.[77][78] Ischemia first affects this region, the subendocardial region, and tissue begins to die within 15–30 minutes of loss of blood supply.[79] The dead tissue is surrounded by a zone of potentially reversible ischemia that progresses to become a full-thickness transmural infarct.[76][79] The initial "wave" of infarction can take place over 3–4 hours.[73][76] These changes are seen on gross pathology and cannot be predicted by the presence or absence of Q waves on an ECG.[78] 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.[28]