Myocardial Infarction
MYOCARDIAL INFARCTION
This term refers to the death of a certain segment of the heart muscle (myocardium), usually the result of a focal complete blockage in one of the main coronary arteries or a branch thereof.
The main cause of myocardial infarction is atherosclerosis in the coronary arteries. Refer to figure 70 for the pathogenesis of myocardial infarction. This event results in impaired contractility of the heart muscle within seconds, and is initially restricted to the affected segment.
The myocardial ischemia or infarction begins in the endocardium (the inner lining of the heart) and spreads to the epicardium (the outer lining of the heart). Irreversible heart damage will occur if the blockage is complete for at least 15-20 minutes. …show more content…
Irreversible damage occurs maximally in the area at risk, and when the occlusion is maintained for 4-6 hours. Most of the damage occurs in the first 2-3 hours. Restoration of flow within the first 4-5 hours is associated with salvage of the heart muscle, but the salvage is greater if flow is restored in the first 1-2 hours. A major determinant of death and illness is the size of the infarct. Increasing the oxygen supply to the involved site of blockage by coronary reperfusion (angioplasty, figures 52, 53, 54, 55, 56b, stents, figures 95a,95b, atherectomy, see figures 56a, 56c) is more effective in salvaging the myocardium than decreasing oxygen demand.
The onset of acute Q-wave myocardial infarction (see figure 94 for normal EKG with a normal Q-wave, which is sharply inscribed, narrow in time of inscription and small in depth compared to the abnormal acute Q-wave type in myocardial infarction, which is deeper and wider in inscription time) occurs commonly in the morning hours shortly after arising, when there is increasing adrenergic activity, as well as increased blood fibrinogen levels and increased platelet (blood cell) adhesiveness. Non Q wave infarction does not show this circadian rhythm.
The traditional concept that myocardial infarctions can be classified as transmural or nontransmural on the basis of the presence or absence of Q waves is misleading, since autopsy studies have demonstrated convincingly that pathologic Q waves may be associated with nontransmural infarction and may be absent with transmural infarction. These misnomers have been replaced by the terms Q-wave infarction and nonQ-wave infarction for transmural and nontransmural infarction, respectively.
The evolution of a non-Q-wave infarction is charcterized by a lack of development of an abnormal Q wave and by the appearance of reversible ST-T-wave changes with ST depression that usually returns to normal over a few days, but occasionally is permanent. Differentiation between these two types of infarctions has become entrenched, since there are major differences in their pathogenesis, clinical manifestations, treatment, and prognosis. The initiating events in the pathogenesis of Q-wave and non-Q-wave infarction are thought to be identical, namely, coronary occlusion induced by thrombus superimposed on a plaque together with vasoconstriction.
There is considerable evidence, however, to indicate that in non-Q-wave infarction, early spontaneus reperfusion occurs, the mechanism of which remains uncertain. In contrast, in Q-wave infarction, the coronary occlusion is sustained at least for a long enough period to result in extensive necrosis.
One explanation for early spontaneous reperfusion is the lack of sustained vasoconstriction, which may contribute to ocusion. The evidence supporting the existence of early spontaneous reperfusion in non-Q-wave infarction is as follows:
1. Coronary angiographic studies performed in the early hours after onset show that only 20-30% of patients have complete coronary occlusion of the infarct-related vessels;but for Q-wave infarction it is about 80 to 90%.
2. Infarct size is routinely much less than observed with Q wave infarction, which is consistent with salvage by early reperfusion.
3. Peak plasma CK levels are reached on an average of 12 to 13 h after onset of symptoms, indicating early washout of the enzyme, as opposed to about 27 h after Q-wave infarction.
4. Reperfusion-induced contraction necrosis is extremely common, as it is in patients who undergo early reperfusion induced by thrombolytic therapy.
5. Acute mortality rates are around 2 to 3 percent, compared with 10 percent for Q-wave infarction.
6. The complications are minimal compared with those after a Q-wave infarction.
7. Finally, the long-term prognosis is characterized by recurrent episodes of reinfarction, so that after about 2 years, survival is the same as that after Q-wave infarction.
Quite often with the initial heart attack over half of the patients have significant obstructive atherosclerosis in only one vessel.
However, in a recent study two fifths of the patients with acute myocardial infarction had angiographic evidence of multiple complex coronary plaques, which were associated with a less favorable in-hospital course. The presence of these plaques with complex morphologic features is the angiographic hallmark of unstable coronary syndromes and correlates with pathologic plaque and thrombus.
Other causes of MI
Carbon monoxide poisoning is one of the occupational toxic risk factors for not only myocardial infarction but also cardiomyopathy.
Firefighters '"chronic" occupational exposure to carbon monoxide results in increased blood concentrations of carboxyhemoglobin, even in nonsmoking firefighters; changes in cardiac serum enzyme levels in one study suggested myocardial (heart) damage.
Increase symptoms in patients known to have coronary disease occur with exposure to carbon monoxide. Carbon monoxide has an affinity for hemoglobin that is much greater than that of oxygen. The cardiac effects are the results of hypoxia. These effects are determined by the degree of carbon monoxide exposure, the hemoglobin concentration, and the presence or absence of coronary or myocardial disease.
A decrease in exercise performance occurs even in normal individuals with low level exposure. Patients with angina pectoris have a greater reduction in exercise tolerance. …show more content…
Carbon monoxide poisoning causes myocardial ischemia most commnoly manifest as ST- and T-wave changes on the ECG and atrial and ventricular arrhythmias. Severe exposure can cause extensive myocardial necrosis and cardiomyopathy. Myocardial infarction may occur as a result of myocardial necrosis without coronary occlusion.
Signs of acute CO intoxication include headache, confusion, visual disturbance, unconsciousness, seizures and lung edema. If untreated severe intoxication can lead to death.
Patients with mild intoxication are likely to recover without specific treatment other than removal from the noxious gas environment. The outlook is uncertain in those severely intoxicated. The severity of the illness often does not correlate with the measured carboxyhemoglobin level but corresponds more closely to the extent and the duration of the exposure.
Patients with any form of CNS impairment, evidence of myocardial ischemia,or carboxyhemoglobin levels above 25% merit aggressive therapeutic intervention. The rationale for treatment with hyperbaric oxygen is based on more rapid removal of the CO from hemoglobin and tissue sites. Because O-2 and CO compete for hemoglobin and many tissue binding sites, hyperbaric oxygenation greatly acclerates CO elimination. Furthermore, O-2 dissolved in plasma under hyperbaric conditions effectively bypasses any impediment to oxygen transport imposed by carboxyhemoglobin. Potentially lethal cerebral hypoxia may be averted as a consequence.Twenty minutes of exposure to 100% oxygen at 2.4 atm absolute will be accompanied by release of CO from the blood equivalent to that obtained after 5 hours of breathing uncontaminated air. Sixty to 90 min of hyperbaric oxygen therapy at this pressure is sufficient to reduce carboxyhemoglobin saturation to well below 10%. Prompt recovery is the rule if treatment can be initiated before extensive irreversible brain injury has occurred.
LABORATORY
The laboratory diagnosis of myocardial infarction
The diagnosis of acute myocardial infarction poses no problem in a patient who presents with shock, diaphoresis, an ashen gray appearance, and crushing substernal chest pain radiating down the left arm. Anyone who has once witnessed this classical presentation will be able to make the diagnosis in the future.
But many patients with acute MI present with less than classical signs and symptoms: indigestion, persistent pain in the back or in the base of the neck, or an unexplained arrhythmia. How is the diagnosis of acute myocardial infarction then established?
In this subset, the first step toward establishing the diagnosis is a high index of suspicion. Signs and symptoms among patients with "possible' or "probable' acute MI are not enough; further investigations are necessary to rule in or rule out the diagnosis. The diagnosis for many of these can be established with an electrocardiogram or a series of ECGs obtained as the infarct evolves. And for decades this was the only modality available other than the history and physical.
About 20 years ago, enzyme panels were introduced to confirm or exclude acute MI among patients with atypical presentations whose ECGs were equivocal. Enzymatic confirmations consisting of CK, SGOT, and LDH were employed initially. Characteristic time-dependent elevations of these enzymes would confirm the diagnosis, and approximate date, of a presumed acute MI. But false-positive CK elevations resulting from intramuscular injections, and nonspecific elevations of SGOT and LDH, limited the usefulness of these panels. About seven years ago, this triad was replaced with an equally sensitive but much more specific panel consisting of total CK and LDH as well as isoenzymes of each.1, 2
So now the laboratory diagnosis of acute MI is a reality. Or is it? Among patients with possible or probable acute MI whose ECGs are equivocal, how well can the lab rule in or rule out the diagnosis? This questions among patients increasing frequency by clinicians and pathologists alike, for it is important to diagnose the smallest acute MI at its earliest stage, while avoiding the significant implications of a false-positive diagnosis. The analogy to the diagnosis of early pregnancy or early malignancy should be apparent.
Individuals erroneously classified as having sustained acute MIs (false positives) run up huge hospital bills, are denied life insurance, are "rated' on their health insurance coverage, and may be restricted in their occupational and recreational activities. Patients with acute MI who fail to be diagnosed on the basis of clinical presentation, ECGs, and lab tests (false negatives) are also ill-served. They are at high risk for sudden death in the immediate post-infarction period; if they survive, they are at high risk for reinfarction in the future.
Failure to establish the diagnosis also precludes medical therapy and life-style modification programs designed to ameliorate positive risk factors for future vascular catastrophes: diabetes, high blood pressure, obesity, smoking, and insufficient exercise.
All lab determinations are subject to false-positive and false-negative results, and isoenzyme tests used to diagnose acute MI are no exception. Isoenzymes of CK have been scrutinized in this regard, since circulating CK-MB is accepted by many physicians as sure proof of an acute MI and as justification for admission to the coronary care unit. But a single CK-MB test tells the clinician nothing!
If no MB activity is demonstrated, it may be because the infarct is of such recent onset that insufficient time has elapsed to detect its presence in the blood. Serial CK-MB determinations are required in this instance to establish a lab diagnosis of acute MI.
On the other hand, the coronary atrtery occlusion may have occurred several days previously, and CK-MB activity since peaked and disappeared. In this case, only the flipped LDH1 and and LDH2 fractions will establish a laboratory diagnosis.
Then there are the false positives. These relate principally to definition of terms and to methodology, although gross and random error obviously occur as well.
CK-MB activity is present in the serum of normal individuals, albeit in small concentrations. The critical question is where does one place the cutoff between normal and abnormal concentrations, knowing that overlap exists between normals and patients who have recently sustained acute MIs?
Two criteria are employed in this regard: the absolute concentration of CK-MB activity in enzyme units per liter of serum, and the percentage of CK activity expressed relative to the total CK activity. CK-MB activity that is less than 3 per cent of the total is not considered pathologic, while a concentration greater than 5 per cent certainly is. A 4 per cent cutoff designed for high-sensitivity, low-specificity must be balanced against a 5 per cent cutoff, which provides higher specificity but a corresponding loss of sensitivity.
Regardless of the percentage of CK activity represented by the MB fraction, the absolute concentration is also significant but does not necessarily reflect damage to mayocardial tissue--all striated muscle contains small amounts of MB activity. Therefore damage to any striated muscle will elevate CK-MB, although such elevations are not pathognomic of acute MI unless the percentage of MB activity is simultaneously increased.
How high must concentrations of MB activity be before they are considered pathologic? Concentrations greater than 20 IU per liter are definitely elevated. There is a gray zone in the range of about 12-20 units, and values less than 12 units are observed among normal individuals without either cardiac or voluntary muscle damage.
Methodology is critical to CK isoenzyme testing.3 Electrophoresis is the most popular and also is the reference method. But several "quick and dirty' assays have been advocated to assist in rapid diagnosis of acute MI, for electrophoresis is tedious and not available in most labs on a Stat basis.
In lieu of electrophoresis, these alternatives employ chromatography, immunoinhibition, radioimmunoassay, and immunochemistry to quantitate MB activity. Although these assays have fairly rapid turnaround times, none provides the correlation to the reference method demanded by clinicians. So the search goes on for the ultimate CK-MB procedure.
The latest entrant into the field is an immunochemical assay based upon some clever monoclonal antibody technology. The procedure employs two monoclonal antibodies, one specific for CK-M and the second specific for CK-B.
The first antibody is bound to a solid phase--sich as a plastic bead--which in turn is incubated with the serum to be tested. The solid phase binds both CK-MM and MB, isoenzymes sharing CK-M activity. The solid phase is then incubated with the second antibody, which is specific for CK-B. A "sandwich' is formed only with solid-phase bound molecules of CK-MB. The second antibody is conveniently coupled to an alkaline phosphatase marker (although other markers could be substituted), making detection of MB activity simple through use of traditional laboratory procedures.
It should be noted that not all CK-MB is biologically active. This immunochemical method will detect both active and inactive forms of the molecule. Thus the assay detects the mass of CK-MB present rather than its biologic activity. (The fact that an alkaline phosphatase marker is employed should not confuse one into believing that he is measuring biologic activity of an enzyme.)
Since an elevated CK-MB is not, per se, an indication of cardiac muscle damage, an elevation is meaningful only activity is concomitantly of MB activity is concomitantly increased. It remains to be seen whether a biologic assay or a mass assay that measures both active and inactive forms to total CK will provide thebest denominator in detecting when the concentration of CK-MB is elevated.
This new procedure has yet to undergo the scrutiny of clinical trials. But its high specificity and ability to quantitate the mass of circulating CK-MB at low concentrations suggest that it may represent a significant advance in laboratory diagnosis.
NSTEMI is an acronym meani ng "non-ST segment elevation myocardial infarction," which is a type of heart attack. This is determined by a electrocardiogram (ECG) test.
Myocardial infarctions (heart attacks) occur when a coronary artery suddenly becomes occluded by a blood clot, causing at least some of the heart muscle being supplied by that artery to become infarcted (that is, to die).
Myocardial infarctions are divided into two types, according to their severity. A NSTEMI is the less severe type.
In a NSTEMI, the blood clot only partly occludes the artery, and as a result only a portion of the heart muscle being supplied by the affected artery dies.
In contrast to the more severe form of heart attack (the STEMI), the NSTEMI does not produce characteristic elevation in the "ST segment" portion of the ECG. (ST segment elevation indicates that a relatively large amount of heart muscle damage is occurring, because the coronary artery is totally blocked). This means that in a NSTEMI, the artery is only partially blocked.
A common problem when a patient has an acute coronary syndrome without ST segment elevation is deciding whether an actual heart attack is occurring or instead whether the patient is simply having unstable angina. Measuring cardiac enzymes, which reflect heart muscle damage, is an important tool in making this distinction.
Laboratory Diagnosis of Myocardial Infarction
| A number of laboratory tests are available. None is completely sensitive and specific for myocardial infarction, particularly in the hours following onset of symptoms. Timing is important, as are correlation with patient symptoms, electrocardiograms, and angiographic studies. The following tests are available as markers for acute myocardial infarction: Creatine Kinase - Total:The total CK is a simple and inexpensive test that is readily available using many laboratory instruments. However, an elevation in total CK is not specific for myocardial injury, because most CK is located in skeletal muscle, and elevations are possible from a variety of non-cardiac conditions. Creatine Kinase - MB Fraction:Creatine kinase can be further subdivided into three isoenzymes: MM, MB, and BB. The MM fraction is present in both cardiac and skeletal muscle, but the MB fraction is much more specific for cardiac muscle: about 15 to 40% of CK in cardiac muscle is MB, while less than 2% in skeletal muscle is MB. The BB fraction (found in brain, bowel, and bladder) is not routinely measured.Thus, CK-MB is a very good marker for acute myocardial injury, because of its excellent specificity, and it rises in serum within 2 to 8 hours of onset of acute myocardial infarction. Serial measurements every 2 to 4 hours for a period of 9 to 12 hours after the patient is first seen will provide a pattern to determine whether the CK-MB is rising, indicative of myocardial injury. The CK-MB is also useful for diagnosis of reinfarction or extensive of an MI because it begins to fall after a day, dissipating in 1 to 3 days, so subsequent elevations are indicative of another event.A "cardiac index" can provide a useful indicator for early MI. This is calculated as a ratio of total CK to CK-MB, and is a sensitive indicator of myocardial injury when the CK-MB is elevated.CK-MB Isoforms:The CK-MB fraction exists in two isoforms called 1 and 2 identified by electrophoretic methodology. The ratio of isoform 2 to 1 can provide information about myocardial injury.An isoform ratio of 1.5 or greater is an excellent indicator for early acute myocardial infarction. CK-MB isoform 2 demonstrates elevation even before CK-MB by laboratory testing. However, the disadvantage of this method is that it is skilled labor intensive because electrophoresis is required, and large numbers of samples cannot be run simultaneously nor continuously. False positive results with congestive heart failure and other conditions can occur.Troponins:Troponin I and T are structural components of cardiac muscle. They are released into the bloodstream with myocardial injury. They are highly specific for myocardial injury--more so than CK-MB--and help to exclude elevations of CK with skeletal muscle trauma. Troponins will begin to increase following MI within 3 to 12 hours, about the same time frame as CK-MB. However, the rate of rise for early infarction may not be as dramatic as for CK-MB.Troponins will remain elevated longer than CK--up to 5 to 9 days for troponin I and up to 2 weeks for troponin T. This makes troponins a superior marker for diagnosing myocardial infarction in the recent past--better than lactate dehydrogenase (LDH). However, this continued elevation has the disadvantage of making it more difficult to diagnose reinfarction or extension of infarction in a patient who has already suffered an initial MI. Troponin T lacks some specificity because elevations can appear with skeletal myopathies and with renal failure.Myoglobin:Myoglobin is a protein found in skeletal and cardiac muscle which binds oxygen. It is a very sensitive indicator of muscle injury. The rise in myoglobin can help to determine the size of an infarction. A negative myoglobin can help to rule out myocardial infarction.. It is elevated even before CK-MB. However, it is not specific for cardiac muscle, and can be elevated with any form of injury to skeletal muscle.Lactate dehydrogenase:The LDH has been supplanted by other tests. It begins to rise in 12 to 24 hours following MI, and peaks in 2 to 3 days, gradually dissipating in 5 to 14 days. Measurement of LDH isoenzymes is necessary for greater specificity for cardiac injury. There are 5 isoenzymes (1 through 5). Ordinarily, isoenzyme 2 is greater than 1, but with myocardial injury, this pattern is "flipped" and 1 is higher than 2. LDH-5 from liver may be increased with centrilobular necrosis from passive congestion with congestive heart failure following ischemic myocardial injury. |
Laboratory Diagnosis of Myocardial Infarction
A number of laboratory biomarkers for myocardial injury are available. None is completely sensitive and specific for myocardial infarction, particularly in the hours following onset of symptoms. Timing is important, as are correlation with patient symptoms, electrocardiograms, and angiographic studies.
The following biomarkers have been described in association with acute myocardial infarction:
Creatine Kinase - Total:
The total CK is a simple and inexpensive test that is readily available using many laboratory instruments. However, an elevation in total CK is not specific for myocardial injury, because most CK is located in skeletal muscle, and elevations are possible from a variety of non-cardiac conditions. (Chattington et al, 1994)
Creatine Kinase - MB Fraction:
Creatine kinase can be further subdivided into three isoenzymes: MM, MB, and BB. The MM fraction is present in both cardiac and skeletal muscle, but the MB fraction is much more specific for cardiac muscle: about 15 to 40% of CK in cardiac muscle is MB, while less than 2% in skeletal muscle is MB. The BB fraction (found in brain, bowel, and bladder) is not routinely measured.
The creatine kinase-MB fraction (CK-MB) is part of total CK and more specific for cardiac muscle that other striated muscle. It tends to increase within 3 to 4 hours of myocardial necrosis, then peak in a day and return to normal within 36 hours. It is less sensitive than troponins. (Saenger and Jaffe, 2007) (Kumar and Cannon, Part I, 2009)
The CK-MB is also useful for diagnosis of reinfarction or extensive of an MI because it begins to fall after a day, so subsequent elevations are indicative of another event. (Chattington et al, 1994)
Troponins:
Troponin I and T are structural components of cardiac muscle. They are released into the bloodstream with myocardial injury. They are highly specific for myocardial injury--more so than CK-MB--and help to exclude elevations of CK with skeletal muscle trauma. Troponins will begin to increase following MI within 3 to 12 hours, about the same time frame as CK-MB. However, the rate of rise for early infarction may not be as dramatic as for CK-MB.
Troponins will remain elevated longer than CK--up to 5 to 10 days for troponin I and up to 2 weeks for troponin T. This makes troponins a superior marker for diagnosing myocardial infarction in the recent past--better than lactate dehydrogenase (LDH). However, this continued elevation has the disadvantage of making it more difficult to diagnose reinfarction or extension of infarction in a patient who has already suffered an initial MI. Troponin T lacks some specificity because elevations can appear with skeletal myopathies and with renal failure. (Kost et al, 1998) (Kumar and Cannon, Part I, 2009)
Myoglobin:
Myoglobin is a protein found in skeletal and cardiac muscle which binds oxygen. It is a very sensitive indicator of muscle injury. However, it is not specific for cardiac muscle, and can be elevated with any form of injury to skeletal muscle. The rise in myoglobin can help to determine the size of an infarction. A negative myoglobin can help to rule out myocardial infarction. It is elevated even before CK-MB. (Kumar and Cannon, Part I, 2009)
BNP:
B-type natriuretic peptide (BNP) is released from ventricular myocardium. BNP release can be stimulated by systolic and diastolic left ventricular dysfunction, acute coronary syndromes, stable coronary heart disease, valvular heart disease, acute and chronic right ventricular failure, and left and right ventricular hypertrophy secondary to arterial or pulmonary hypertension. BNP is a marker for heart failure. (Saenger and Jaffe, 2007)
CRP:
C-reactive protein (CRP) is an acute phase protein elevated when inflammation is present. Since inflammation is part of atheroma formation, then CRP may reflect the extent of atheromatous plaque formation and predict risk for acute coronary events. However, CRP lacks specificity for vascular events. (Saenger and Jaffe, 2007)
c
This term refers to the death of a certain segment of the heart muscle (myocardium), usually the result of a focal complete blockage in one of the main coronary arteries or a branch thereof.
The main cause of myocardial infarction is atherosclerosis in the coronary arteries. Refer to figure 70 for the pathogenesis of myocardial infarction. This event results in impaired contractility of the heart muscle within seconds, and is initially restricted to the affected segment.
The myocardial ischemia or infarction begins in the endocardium (the inner lining of the heart) and spreads to the epicardium (the outer lining of the heart). Irreversible heart damage will occur if the blockage is complete for at least 15-20 minutes. …show more content…
Irreversible damage occurs maximally in the area at risk, and when the occlusion is maintained for 4-6 hours. Most of the damage occurs in the first 2-3 hours. Restoration of flow within the first 4-5 hours is associated with salvage of the heart muscle, but the salvage is greater if flow is restored in the first 1-2 hours. A major determinant of death and illness is the size of the infarct. Increasing the oxygen supply to the involved site of blockage by coronary reperfusion (angioplasty, figures 52, 53, 54, 55, 56b, stents, figures 95a,95b, atherectomy, see figures 56a, 56c) is more effective in salvaging the myocardium than decreasing oxygen demand.
The onset of acute Q-wave myocardial infarction (see figure 94 for normal EKG with a normal Q-wave, which is sharply inscribed, narrow in time of inscription and small in depth compared to the abnormal acute Q-wave type in myocardial infarction, which is deeper and wider in inscription time) occurs commonly in the morning hours shortly after arising, when there is increasing adrenergic activity, as well as increased blood fibrinogen levels and increased platelet (blood cell) adhesiveness. Non Q wave infarction does not show this circadian rhythm.
The traditional concept that myocardial infarctions can be classified as transmural or nontransmural on the basis of the presence or absence of Q waves is misleading, since autopsy studies have demonstrated convincingly that pathologic Q waves may be associated with nontransmural infarction and may be absent with transmural infarction. These misnomers have been replaced by the terms Q-wave infarction and nonQ-wave infarction for transmural and nontransmural infarction, respectively.
The evolution of a non-Q-wave infarction is charcterized by a lack of development of an abnormal Q wave and by the appearance of reversible ST-T-wave changes with ST depression that usually returns to normal over a few days, but occasionally is permanent. Differentiation between these two types of infarctions has become entrenched, since there are major differences in their pathogenesis, clinical manifestations, treatment, and prognosis. The initiating events in the pathogenesis of Q-wave and non-Q-wave infarction are thought to be identical, namely, coronary occlusion induced by thrombus superimposed on a plaque together with vasoconstriction.
There is considerable evidence, however, to indicate that in non-Q-wave infarction, early spontaneus reperfusion occurs, the mechanism of which remains uncertain. In contrast, in Q-wave infarction, the coronary occlusion is sustained at least for a long enough period to result in extensive necrosis.
One explanation for early spontaneous reperfusion is the lack of sustained vasoconstriction, which may contribute to ocusion. The evidence supporting the existence of early spontaneous reperfusion in non-Q-wave infarction is as follows:
1. Coronary angiographic studies performed in the early hours after onset show that only 20-30% of patients have complete coronary occlusion of the infarct-related vessels;but for Q-wave infarction it is about 80 to 90%.
2. Infarct size is routinely much less than observed with Q wave infarction, which is consistent with salvage by early reperfusion.
3. Peak plasma CK levels are reached on an average of 12 to 13 h after onset of symptoms, indicating early washout of the enzyme, as opposed to about 27 h after Q-wave infarction.
4. Reperfusion-induced contraction necrosis is extremely common, as it is in patients who undergo early reperfusion induced by thrombolytic therapy.
5. Acute mortality rates are around 2 to 3 percent, compared with 10 percent for Q-wave infarction.
6. The complications are minimal compared with those after a Q-wave infarction.
7. Finally, the long-term prognosis is characterized by recurrent episodes of reinfarction, so that after about 2 years, survival is the same as that after Q-wave infarction.
Quite often with the initial heart attack over half of the patients have significant obstructive atherosclerosis in only one vessel.
However, in a recent study two fifths of the patients with acute myocardial infarction had angiographic evidence of multiple complex coronary plaques, which were associated with a less favorable in-hospital course. The presence of these plaques with complex morphologic features is the angiographic hallmark of unstable coronary syndromes and correlates with pathologic plaque and thrombus.
Other causes of MI
Carbon monoxide poisoning is one of the occupational toxic risk factors for not only myocardial infarction but also cardiomyopathy.
Firefighters '"chronic" occupational exposure to carbon monoxide results in increased blood concentrations of carboxyhemoglobin, even in nonsmoking firefighters; changes in cardiac serum enzyme levels in one study suggested myocardial (heart) damage.
Increase symptoms in patients known to have coronary disease occur with exposure to carbon monoxide. Carbon monoxide has an affinity for hemoglobin that is much greater than that of oxygen. The cardiac effects are the results of hypoxia. These effects are determined by the degree of carbon monoxide exposure, the hemoglobin concentration, and the presence or absence of coronary or myocardial disease.
A decrease in exercise performance occurs even in normal individuals with low level exposure. Patients with angina pectoris have a greater reduction in exercise tolerance. …show more content…
Carbon monoxide poisoning causes myocardial ischemia most commnoly manifest as ST- and T-wave changes on the ECG and atrial and ventricular arrhythmias. Severe exposure can cause extensive myocardial necrosis and cardiomyopathy. Myocardial infarction may occur as a result of myocardial necrosis without coronary occlusion.
Signs of acute CO intoxication include headache, confusion, visual disturbance, unconsciousness, seizures and lung edema. If untreated severe intoxication can lead to death.
Patients with mild intoxication are likely to recover without specific treatment other than removal from the noxious gas environment. The outlook is uncertain in those severely intoxicated. The severity of the illness often does not correlate with the measured carboxyhemoglobin level but corresponds more closely to the extent and the duration of the exposure.
Patients with any form of CNS impairment, evidence of myocardial ischemia,or carboxyhemoglobin levels above 25% merit aggressive therapeutic intervention. The rationale for treatment with hyperbaric oxygen is based on more rapid removal of the CO from hemoglobin and tissue sites. Because O-2 and CO compete for hemoglobin and many tissue binding sites, hyperbaric oxygenation greatly acclerates CO elimination. Furthermore, O-2 dissolved in plasma under hyperbaric conditions effectively bypasses any impediment to oxygen transport imposed by carboxyhemoglobin. Potentially lethal cerebral hypoxia may be averted as a consequence.Twenty minutes of exposure to 100% oxygen at 2.4 atm absolute will be accompanied by release of CO from the blood equivalent to that obtained after 5 hours of breathing uncontaminated air. Sixty to 90 min of hyperbaric oxygen therapy at this pressure is sufficient to reduce carboxyhemoglobin saturation to well below 10%. Prompt recovery is the rule if treatment can be initiated before extensive irreversible brain injury has occurred.
LABORATORY
The laboratory diagnosis of myocardial infarction
The diagnosis of acute myocardial infarction poses no problem in a patient who presents with shock, diaphoresis, an ashen gray appearance, and crushing substernal chest pain radiating down the left arm. Anyone who has once witnessed this classical presentation will be able to make the diagnosis in the future.
But many patients with acute MI present with less than classical signs and symptoms: indigestion, persistent pain in the back or in the base of the neck, or an unexplained arrhythmia. How is the diagnosis of acute myocardial infarction then established?
In this subset, the first step toward establishing the diagnosis is a high index of suspicion. Signs and symptoms among patients with "possible' or "probable' acute MI are not enough; further investigations are necessary to rule in or rule out the diagnosis. The diagnosis for many of these can be established with an electrocardiogram or a series of ECGs obtained as the infarct evolves. And for decades this was the only modality available other than the history and physical.
About 20 years ago, enzyme panels were introduced to confirm or exclude acute MI among patients with atypical presentations whose ECGs were equivocal. Enzymatic confirmations consisting of CK, SGOT, and LDH were employed initially. Characteristic time-dependent elevations of these enzymes would confirm the diagnosis, and approximate date, of a presumed acute MI. But false-positive CK elevations resulting from intramuscular injections, and nonspecific elevations of SGOT and LDH, limited the usefulness of these panels. About seven years ago, this triad was replaced with an equally sensitive but much more specific panel consisting of total CK and LDH as well as isoenzymes of each.1, 2
So now the laboratory diagnosis of acute MI is a reality. Or is it? Among patients with possible or probable acute MI whose ECGs are equivocal, how well can the lab rule in or rule out the diagnosis? This questions among patients increasing frequency by clinicians and pathologists alike, for it is important to diagnose the smallest acute MI at its earliest stage, while avoiding the significant implications of a false-positive diagnosis. The analogy to the diagnosis of early pregnancy or early malignancy should be apparent.
Individuals erroneously classified as having sustained acute MIs (false positives) run up huge hospital bills, are denied life insurance, are "rated' on their health insurance coverage, and may be restricted in their occupational and recreational activities. Patients with acute MI who fail to be diagnosed on the basis of clinical presentation, ECGs, and lab tests (false negatives) are also ill-served. They are at high risk for sudden death in the immediate post-infarction period; if they survive, they are at high risk for reinfarction in the future.
Failure to establish the diagnosis also precludes medical therapy and life-style modification programs designed to ameliorate positive risk factors for future vascular catastrophes: diabetes, high blood pressure, obesity, smoking, and insufficient exercise.
All lab determinations are subject to false-positive and false-negative results, and isoenzyme tests used to diagnose acute MI are no exception. Isoenzymes of CK have been scrutinized in this regard, since circulating CK-MB is accepted by many physicians as sure proof of an acute MI and as justification for admission to the coronary care unit. But a single CK-MB test tells the clinician nothing!
If no MB activity is demonstrated, it may be because the infarct is of such recent onset that insufficient time has elapsed to detect its presence in the blood. Serial CK-MB determinations are required in this instance to establish a lab diagnosis of acute MI.
On the other hand, the coronary atrtery occlusion may have occurred several days previously, and CK-MB activity since peaked and disappeared. In this case, only the flipped LDH1 and and LDH2 fractions will establish a laboratory diagnosis.
Then there are the false positives. These relate principally to definition of terms and to methodology, although gross and random error obviously occur as well.
CK-MB activity is present in the serum of normal individuals, albeit in small concentrations. The critical question is where does one place the cutoff between normal and abnormal concentrations, knowing that overlap exists between normals and patients who have recently sustained acute MIs?
Two criteria are employed in this regard: the absolute concentration of CK-MB activity in enzyme units per liter of serum, and the percentage of CK activity expressed relative to the total CK activity. CK-MB activity that is less than 3 per cent of the total is not considered pathologic, while a concentration greater than 5 per cent certainly is. A 4 per cent cutoff designed for high-sensitivity, low-specificity must be balanced against a 5 per cent cutoff, which provides higher specificity but a corresponding loss of sensitivity.
Regardless of the percentage of CK activity represented by the MB fraction, the absolute concentration is also significant but does not necessarily reflect damage to mayocardial tissue--all striated muscle contains small amounts of MB activity. Therefore damage to any striated muscle will elevate CK-MB, although such elevations are not pathognomic of acute MI unless the percentage of MB activity is simultaneously increased.
How high must concentrations of MB activity be before they are considered pathologic? Concentrations greater than 20 IU per liter are definitely elevated. There is a gray zone in the range of about 12-20 units, and values less than 12 units are observed among normal individuals without either cardiac or voluntary muscle damage.
Methodology is critical to CK isoenzyme testing.3 Electrophoresis is the most popular and also is the reference method. But several "quick and dirty' assays have been advocated to assist in rapid diagnosis of acute MI, for electrophoresis is tedious and not available in most labs on a Stat basis.
In lieu of electrophoresis, these alternatives employ chromatography, immunoinhibition, radioimmunoassay, and immunochemistry to quantitate MB activity. Although these assays have fairly rapid turnaround times, none provides the correlation to the reference method demanded by clinicians. So the search goes on for the ultimate CK-MB procedure.
The latest entrant into the field is an immunochemical assay based upon some clever monoclonal antibody technology. The procedure employs two monoclonal antibodies, one specific for CK-M and the second specific for CK-B.
The first antibody is bound to a solid phase--sich as a plastic bead--which in turn is incubated with the serum to be tested. The solid phase binds both CK-MM and MB, isoenzymes sharing CK-M activity. The solid phase is then incubated with the second antibody, which is specific for CK-B. A "sandwich' is formed only with solid-phase bound molecules of CK-MB. The second antibody is conveniently coupled to an alkaline phosphatase marker (although other markers could be substituted), making detection of MB activity simple through use of traditional laboratory procedures.
It should be noted that not all CK-MB is biologically active. This immunochemical method will detect both active and inactive forms of the molecule. Thus the assay detects the mass of CK-MB present rather than its biologic activity. (The fact that an alkaline phosphatase marker is employed should not confuse one into believing that he is measuring biologic activity of an enzyme.)
Since an elevated CK-MB is not, per se, an indication of cardiac muscle damage, an elevation is meaningful only activity is concomitantly of MB activity is concomitantly increased. It remains to be seen whether a biologic assay or a mass assay that measures both active and inactive forms to total CK will provide thebest denominator in detecting when the concentration of CK-MB is elevated.
This new procedure has yet to undergo the scrutiny of clinical trials. But its high specificity and ability to quantitate the mass of circulating CK-MB at low concentrations suggest that it may represent a significant advance in laboratory diagnosis.
NSTEMI is an acronym meani ng "non-ST segment elevation myocardial infarction," which is a type of heart attack. This is determined by a electrocardiogram (ECG) test.
Myocardial infarctions (heart attacks) occur when a coronary artery suddenly becomes occluded by a blood clot, causing at least some of the heart muscle being supplied by that artery to become infarcted (that is, to die).
Myocardial infarctions are divided into two types, according to their severity. A NSTEMI is the less severe type.
In a NSTEMI, the blood clot only partly occludes the artery, and as a result only a portion of the heart muscle being supplied by the affected artery dies.
In contrast to the more severe form of heart attack (the STEMI), the NSTEMI does not produce characteristic elevation in the "ST segment" portion of the ECG. (ST segment elevation indicates that a relatively large amount of heart muscle damage is occurring, because the coronary artery is totally blocked). This means that in a NSTEMI, the artery is only partially blocked.
A common problem when a patient has an acute coronary syndrome without ST segment elevation is deciding whether an actual heart attack is occurring or instead whether the patient is simply having unstable angina. Measuring cardiac enzymes, which reflect heart muscle damage, is an important tool in making this distinction.
Laboratory Diagnosis of Myocardial Infarction
| A number of laboratory tests are available. None is completely sensitive and specific for myocardial infarction, particularly in the hours following onset of symptoms. Timing is important, as are correlation with patient symptoms, electrocardiograms, and angiographic studies. The following tests are available as markers for acute myocardial infarction: Creatine Kinase - Total:The total CK is a simple and inexpensive test that is readily available using many laboratory instruments. However, an elevation in total CK is not specific for myocardial injury, because most CK is located in skeletal muscle, and elevations are possible from a variety of non-cardiac conditions. Creatine Kinase - MB Fraction:Creatine kinase can be further subdivided into three isoenzymes: MM, MB, and BB. The MM fraction is present in both cardiac and skeletal muscle, but the MB fraction is much more specific for cardiac muscle: about 15 to 40% of CK in cardiac muscle is MB, while less than 2% in skeletal muscle is MB. The BB fraction (found in brain, bowel, and bladder) is not routinely measured.Thus, CK-MB is a very good marker for acute myocardial injury, because of its excellent specificity, and it rises in serum within 2 to 8 hours of onset of acute myocardial infarction. Serial measurements every 2 to 4 hours for a period of 9 to 12 hours after the patient is first seen will provide a pattern to determine whether the CK-MB is rising, indicative of myocardial injury. The CK-MB is also useful for diagnosis of reinfarction or extensive of an MI because it begins to fall after a day, dissipating in 1 to 3 days, so subsequent elevations are indicative of another event.A "cardiac index" can provide a useful indicator for early MI. This is calculated as a ratio of total CK to CK-MB, and is a sensitive indicator of myocardial injury when the CK-MB is elevated.CK-MB Isoforms:The CK-MB fraction exists in two isoforms called 1 and 2 identified by electrophoretic methodology. The ratio of isoform 2 to 1 can provide information about myocardial injury.An isoform ratio of 1.5 or greater is an excellent indicator for early acute myocardial infarction. CK-MB isoform 2 demonstrates elevation even before CK-MB by laboratory testing. However, the disadvantage of this method is that it is skilled labor intensive because electrophoresis is required, and large numbers of samples cannot be run simultaneously nor continuously. False positive results with congestive heart failure and other conditions can occur.Troponins:Troponin I and T are structural components of cardiac muscle. They are released into the bloodstream with myocardial injury. They are highly specific for myocardial injury--more so than CK-MB--and help to exclude elevations of CK with skeletal muscle trauma. Troponins will begin to increase following MI within 3 to 12 hours, about the same time frame as CK-MB. However, the rate of rise for early infarction may not be as dramatic as for CK-MB.Troponins will remain elevated longer than CK--up to 5 to 9 days for troponin I and up to 2 weeks for troponin T. This makes troponins a superior marker for diagnosing myocardial infarction in the recent past--better than lactate dehydrogenase (LDH). However, this continued elevation has the disadvantage of making it more difficult to diagnose reinfarction or extension of infarction in a patient who has already suffered an initial MI. Troponin T lacks some specificity because elevations can appear with skeletal myopathies and with renal failure.Myoglobin:Myoglobin is a protein found in skeletal and cardiac muscle which binds oxygen. It is a very sensitive indicator of muscle injury. The rise in myoglobin can help to determine the size of an infarction. A negative myoglobin can help to rule out myocardial infarction.. It is elevated even before CK-MB. However, it is not specific for cardiac muscle, and can be elevated with any form of injury to skeletal muscle.Lactate dehydrogenase:The LDH has been supplanted by other tests. It begins to rise in 12 to 24 hours following MI, and peaks in 2 to 3 days, gradually dissipating in 5 to 14 days. Measurement of LDH isoenzymes is necessary for greater specificity for cardiac injury. There are 5 isoenzymes (1 through 5). Ordinarily, isoenzyme 2 is greater than 1, but with myocardial injury, this pattern is "flipped" and 1 is higher than 2. LDH-5 from liver may be increased with centrilobular necrosis from passive congestion with congestive heart failure following ischemic myocardial injury. |
Laboratory Diagnosis of Myocardial Infarction
A number of laboratory biomarkers for myocardial injury are available. None is completely sensitive and specific for myocardial infarction, particularly in the hours following onset of symptoms. Timing is important, as are correlation with patient symptoms, electrocardiograms, and angiographic studies.
The following biomarkers have been described in association with acute myocardial infarction:
Creatine Kinase - Total:
The total CK is a simple and inexpensive test that is readily available using many laboratory instruments. However, an elevation in total CK is not specific for myocardial injury, because most CK is located in skeletal muscle, and elevations are possible from a variety of non-cardiac conditions. (Chattington et al, 1994)
Creatine Kinase - MB Fraction:
Creatine kinase can be further subdivided into three isoenzymes: MM, MB, and BB. The MM fraction is present in both cardiac and skeletal muscle, but the MB fraction is much more specific for cardiac muscle: about 15 to 40% of CK in cardiac muscle is MB, while less than 2% in skeletal muscle is MB. The BB fraction (found in brain, bowel, and bladder) is not routinely measured.
The creatine kinase-MB fraction (CK-MB) is part of total CK and more specific for cardiac muscle that other striated muscle. It tends to increase within 3 to 4 hours of myocardial necrosis, then peak in a day and return to normal within 36 hours. It is less sensitive than troponins. (Saenger and Jaffe, 2007) (Kumar and Cannon, Part I, 2009)
The CK-MB is also useful for diagnosis of reinfarction or extensive of an MI because it begins to fall after a day, so subsequent elevations are indicative of another event. (Chattington et al, 1994)
Troponins:
Troponin I and T are structural components of cardiac muscle. They are released into the bloodstream with myocardial injury. They are highly specific for myocardial injury--more so than CK-MB--and help to exclude elevations of CK with skeletal muscle trauma. Troponins will begin to increase following MI within 3 to 12 hours, about the same time frame as CK-MB. However, the rate of rise for early infarction may not be as dramatic as for CK-MB.
Troponins will remain elevated longer than CK--up to 5 to 10 days for troponin I and up to 2 weeks for troponin T. This makes troponins a superior marker for diagnosing myocardial infarction in the recent past--better than lactate dehydrogenase (LDH). However, this continued elevation has the disadvantage of making it more difficult to diagnose reinfarction or extension of infarction in a patient who has already suffered an initial MI. Troponin T lacks some specificity because elevations can appear with skeletal myopathies and with renal failure. (Kost et al, 1998) (Kumar and Cannon, Part I, 2009)
Myoglobin:
Myoglobin is a protein found in skeletal and cardiac muscle which binds oxygen. It is a very sensitive indicator of muscle injury. However, it is not specific for cardiac muscle, and can be elevated with any form of injury to skeletal muscle. The rise in myoglobin can help to determine the size of an infarction. A negative myoglobin can help to rule out myocardial infarction. It is elevated even before CK-MB. (Kumar and Cannon, Part I, 2009)
BNP:
B-type natriuretic peptide (BNP) is released from ventricular myocardium. BNP release can be stimulated by systolic and diastolic left ventricular dysfunction, acute coronary syndromes, stable coronary heart disease, valvular heart disease, acute and chronic right ventricular failure, and left and right ventricular hypertrophy secondary to arterial or pulmonary hypertension. BNP is a marker for heart failure. (Saenger and Jaffe, 2007)
CRP:
C-reactive protein (CRP) is an acute phase protein elevated when inflammation is present. Since inflammation is part of atheroma formation, then CRP may reflect the extent of atheromatous plaque formation and predict risk for acute coronary events. However, CRP lacks specificity for vascular events. (Saenger and Jaffe, 2007)
c