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Dear All,
Myocardial infarction results in death of myocardial cells served by the effected artery after about30 minutes of anoxia.
The acute inflammatory response, as a consequence of cell death, results in fever, leukocytosis, and increased concentrations of acute phase reactant proteins in the circulation (determined in the clinical laboratory most commonly by the ESR but better by measurement of C-reactive protein).
Cardiac enzymes are proteins from heart muscle cells that are released into the bloodstream when heart muscle is damaged, such as during a myocardial infarction (MI). By measuring blood levels of cardiac enzymes, doctors can tell whether heart muscle damage has recently occurred.
Cardiac biomarkers should be measured in all patients who present with chest discomfort consistent with acute coronary syndrome (ACS). Elevations of cardiac enzyme levels should be interpreted in the context of clinical and ECG findings.
Indications for measurement of cardiac enzymes
- Any patient presenting with a possible acute coronary syndrome (ACS).
- Routinely following percutaneous coronary intervention (PCI).
- Routinely following surgical revascularization (coronary artery bypass graft (CABG)).
The enzymes routinely measured in the clinical laboratory for the purpose of diagnosing and monitoring myocardial infarction include Creatine kinase (CK), aspartate amino transferases (sGOT or AST), and lactate dehydrogenase (LDH).
These enzymes are present in sufficiently high content in myocardial tissue so that the death of a relatively small amount of tissue results in a substantial increase in measured enzyme activity in serum.
1) - Transaminases and Dehydrogenases:
= Aspartate transaminase and lactate dehydrogenase were used in the past, but have been superseded.
= Laboratory tests used in the diagnosis of myocardial infarction include the following:
n Cardiac biomarkers/enzymes: The American College of Cardiology/American Heart Association (ACC/AHA) guidelines on unstable angina/NSTEMI (non–ST-segment elevation myocardial infarction) recommend that in patients with suspected myocardial infarction, cardiac biomarkers should be measured.
n Serum activity of AST is noticeably increased after about12 hours, peaks between1-2 days, and returns to normal by the3rd to5th day.
n LDH activity increases last, after about18 hours post MI, peaks between the second and third day and remains elevated for about a week.
= Improved specificity is provided by determining isoenzymes because isoenzyme distributions are sometimes significantly different for different tissues and a particular isoenzyme distribution is highly characteristic of a particular tissue.
a- AST Isoenzymes:
n AST isoenzymes are of NO clinical value. AST activity is exhibited by two isoenzymes; one from the cytosol and the other of mitochondrial origin.
n Almost all serum AST activity is due to the cytosol isoenzyme, even after damage to tissues with substantial mitochondrial isoenzyme content.
n Since the mitochondrial isoenzyme has such a short circulating lifetime, its activity is rapidly eliminated.
b- LDH Isoenzymes:
n LDH is a tetramer composed of two different subunits, M and H. Five different isoenzymes are possible: M4, M3H, M2H2, MH3, and H4, and all five are present in different tissue in different relative amounts.
n The five different isoenzymes are resolved by electrophoresis and determination of the LDH isoenzyme distribution by electrophoresis is a commonly performed clinical laboratory test.
n The predominant LDH isoenzyme in liver and skeletal muscle is M4 (LDH-5) and the predominant cardiac isoenzyme is H4 (LDH-1).
n The LDH isoenzyme distribution in normal serum is characterized by the major band being MH3 (LDH-2).
n When total LDH activity is increased from muscle or liver disease, the LDH-5 band becomes dominant. Increased LDH activity from MI is characterized by a predominance of the LDH-1 band.
n The change from the dominance of the LDH-2 band in normal serum to the dominance of the LDH-1 band is called the "LDH flip" and its occurrence is considered diagnostic for MI.
n However, the major LDH isoenzyme in erythrocytes is LDH-1so that hemolysis, either intravascular or in the collected blood specimen, may also cause the LDH flip.
= Therefore, measuring cardiac enzymes is often an important step in diagnosing MIs. Current clinical practice is to measure two different cardiac enzymes when an MI is suspected: Creatine kinase (CK), and troponin (T).
2) - Creatine kinase
- Myocardial muscle Creatine kinase (CK-MB) is found mainly in the heart.
- CK-MB levels increase within3-12 hours of onset of chest pain (it is released into the bloodstream4 to6 hours after heart cell damage occurs), reach peak values within24 hours, and return to baseline after48-72 hours.
- Sensitivity and specificity are not as high as for troponin levels.
- Elevated CK levels usually, but not always, indicate heart muscle damage. CK levels sometimes can be increased with damage to other kinds of cells as well.
- It is evident that CK diffuses out of the necrotic region earliest and most rapidly and LDH latest and most slowly.
- The disappearance rates of the different enzymes following their increase from MI are consistent with what is known about their degradation rates and the isoenzyme distribution in cardiac tissue.
3) - Troponins T and I
- Troponin is a contractile protein that normally is not found in serum. It is released only when myocardial necrosis occurs.
- Cardiac troponins T and I are highly sensitive and specific for cardiac damage. Troponin I and T are of equal clinical value. Both are the preferred markers for myocardial injury as they have the highest sensitivities and specificities for the diagnosis of acute myocardial infarction (ACS).
- Serum levels increase within3-12 hours from the onset of chest pain, peak at24-48 hours, and return to baseline over5-14 days.
- Troponin levels may not be detectable for six hours after the onset of myocardial cell injury. The most sensitive early marker for myocardial infarction is myoglobin.
- T is released into the bloodstream2 to6 hours after heart cell damage, and blood levels peak in12 to26 hours. Elevated levels of T are regarded as a more reliable indicator of heart muscle damage than elevated CK levels.
- Troponin levels should be measured at presentation and again10-12 hours after the onset of symptoms. When there is uncertainty regarding the time of symptom onset, troponin should be measured at12 hours after the presentation.
- The risk of death from an acute coronary syndrome (ACS) is directly related to troponin level and patients with no detectable troponins have a good short-term prognosis.
- Elevated troponin levels can occur in patients without an ACS and are associated with adverse outcomes in many other clinical situations, including congestive heart failure, sepsis, acute pulmonary embolism and chronic kidney disease. Other cardiac causes include myocarditis and aortic dissection.
Notes:
n Because T is an "earlier" marker of cardiac cell damage than CK, and because it is somewhat more accurate at indicating heart cell damage than CK, T is the preferred marker today for diagnosing MI. Both of these cardiac proteins are routinely measured, however, in patients suspected of having MI.
n Patients with negative cardiac biomarkers within6 hours of the onset of symptoms that are consistent with ACS should have biomarkers re-measured in the timeframe of8 to12 hours after the onset of symptoms. Peak circulating enzyme levels tend to occur earlier and are often higher following successful thrombolytic therapy.
4) - Myoglobin levels
- Myoglobin is found in cardiac and skeletal muscle.
- It is released more rapidly from infarcted myocardium than troponin and CK-MB and may be detected as early as2 hours after an acute myocardial infarction.
- Myoglobin has high sensitivity but poor specificity. It may be useful for the early detection of myocardial infarction.
5) - Natriuretic peptides
- Studies in several types of acute coronary syndromes (ACSs) have shown that elevated levels of natriuretic peptides, e.g. B-type natriuretic peptide (BNP), are independently associated with adverse outcomes – especially mortality.
6) - Other findings
- Leukocytosis may be seen within several hours after an acute myocardial infarction. It peaks in2-4 days and returns to normal levels within1 week.
- Patients without biochemical evidence of myocardial necrosis but with elevated C-reactive protein (CRP) level are at increased risk of a subsequent ischaemic event.
- Erythrocyte sedimentation rate (ESR) rises above reference range values within3 days and may remain elevated for weeks.
7) - Future developments
- There are a number of novel biomarkers under investigation, but none has been tested and proven to alter outcome of therapeutic intervention.
- Although some have improved prediction of outcome in acute myocardial infarction, none has been demonstrated to alter the outcome of a particular therapy or management strategy.
- Heart-type fatty acid binding protein and copeptin (in combination with cardiac troponin) diagnose myocardial infarction or acute coronary syndrome (ACS) in the early hours following symptoms.
- Mid-regional pro-atrial natriuretic peptide, ST2, C-terminal pro-endothelin1, mid-regional pro-adrenomedullin and copeptin all provide information in predicting death and heart failure.
- Growth differentiation factor-15 and high-sensitivity C-reactive protein (CRP) may predict death following an acute coronary syndrome (ACS).
- Pregnancy-associated plasma protein A levels following chest pain predict risk of myocardial infarction and revascularization.
It is better to know that:
A. The characteristic time course of the enzyme elevations is clinically useful since it demonstrates that the extent of the elevation of a particular enzyme in serum depends upon the time period between when a blood specimen is drawn and when the MI occurred.
B. In a blood specimen drawn only several hours after an MI, CPK provides the most sensitive diagnostic information and may be the only enzyme which is elevated.
C. If MI is not associated with marked chest pain, a not uncommon occurrence, and several days elapse before the symptoms of feeling tired and run down causes a visit to the physician, then LDH may be the only enzyme which is elevated.
D. Serum enzyme activities are routinely monitored during the post MI period in order to evaluate patients' progress and to obtain diagnostic information about possible complications. Re-infarction will cause the enzymes to increase again, with CK again increasing earliest and LDH last.
E. Heart failure is a complication which is indicated by rapid increases in AST, ALT and LDH (but with no CK increase) from passive liver congestion. When adequate cardiac output is reestablished, LDH activity decreases rapidly in such cases because of the short circulating lifetime of the major liver LDH isoenzymes (LDH5 or M4).
F. The relatively high content of CK, AST and LDH in cardiac tissue accounts for the clinical usefulness of measuring the activity of these enzymes in serum to diagnosis and monitor MI.
G. However, other tissues are also richly endowed with these enzymes. LDH, which catalyzes the terminal step in glycolysis, is present in all cells since glycolsis is a universal metabolic process.
H. Skeletal muscle has a particularly high content of LDH, AST and CPK. Liver has a high content of LDH and AST. Erythrocytes have appreciable LDH and AST activity. It is evident that elevations of these three enzymes are not particularly specific for myocardium.
Best regards,
Lubna
CKMB
TROBONİN I
TROBONİN T
LDH
AST
The approximate circulating half lifes of the different enzymes and isoenzymes are shown below:
mitochondrial AST -------1 hr. LDH-5 (M4) -------12 hrs. CK -------18 hrs. cytoplasmic AST -------1 day ALT -------2 days LDH-1 (H4) -------5 days
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