acute myocardial infarctionIn an attempt to standardize the diagnostic criteria of acute myocardial infarction, the World Health Organization (WHO) in 1959 proposed a classification now referred to as the two-out-of-three criteria, namely, the presence of two or more of the following: chest pain, elevated plasma enzymes or new Q waves on the electrocardiogram. The criteria served a very important function and rapidly became the gold standard throughout the world.

Since that time, diagnostic techniques have evolved considerably with much improved sensitivity and specificity. In 1959, LDH isoenzymes as diagnostic markers had just been introduced, but the data were too scanty to be incorporated into a classification applicable for routine clinical use. In 1959, Dreyfus et al introduced plasma total creatine kinase (CK) and in 1966 Van der Veen et al introduced the isoenzyme forms as diagnostic markers for myocardial infarction. The use of LDH isoenzymes became more widespread in the 1960s and C K isoenzymes in the 1970s. In the 1970s, another tool, diagnostic myocardial imaging, was introduced using technetium pyrophosphate which was quickly followed by techniques using several other isotopes.

There is now considerable agreement that an elevated plasma MBCK is the most sensitive and specific diagnostic marker, as well as the most cost-effective. The use of plasma C K isoenzymes as diagnostic markers is now widespread, and elevated plasma MBCK has become the conventionally accepted hallmark of acute myocardial infarction. The advantages of С К isoenzymes over LDH, in addition to its greater specificity, relate to its more rapid release from injured tissues, more rapid clearance from the plasma, and the recent availability of sensitive and convenient quantitativeisoenzymes assays for CK isoenzymes. Using one of the sensitive quantitative assays, a significant elevation of plasma MBCK can be detected within four hours of onset of infarction and peak plasma values are, on the average, reached within 24 hours. Since it requires two to four hours to reach the hospital, in most patients a significantly elevated plasma MBCK is present at the time of hospital admission. There is still no satisfactory assay for quantifying individual LDH isoenzyme activity, separation is by electrophoresis, and for specificity one must demonstrate that LDH-1 activity exceeds that of LDH-2 activity which is sometimes difficult with the conventional semiquantitative technique of densitometry. However, as a test for the diagnosis of myocardial infarction, it is highly effective and, despite slower release of LDH with peak values reached at 48 to 72 hours, LDH has a diagnostic advantage in latecomers since plasma values remain elevated for ten to 14 days.

Publications arranged with My Canadian Pharmacy’s pharmaceutists on the subject of acute myocardial infarction still state adherence to the two out of three criteria frequently without referencing the WHO report, presumably because it is the only recognized standard accepted by reviewers. Despite this rhetoric claim, in practice one almost always confirms the diagnosis of myocardial infarction on the basis of serial elevations in either CK or LDH isoenzymes. The need for a recommended uniform diagnostic criteria in view of the many assays available for isoenzymes is probably essential, and would be best developed by a body with world-wide recognition such as the WHO. At present, while either CK or LDH isoenzymes are the sole markers relied upon to confirm the diagnosis of myocardial infarction, many hospitals continue to perform on a routine basis the ASP (SGOT), HBD and, in some cases, SGPT presumably for the sake of nostalgia.

Furthermore, these enzymes are often analyzed over two to three days as opposed to frequent sampling for MBCK over 12 to 24 hours. At a time when health care costs are of great concern, uniformity and efficiency would significantly help to defray the continuing escalation of medical care costs. Patients in whom plasma MBCK remains normal as determined serially over 12 to 24 hours can be transferred from the expensive care of a coronary care unit to that of a more appropriate and less expensive care of the general hospital ward. On the average, only about 30 to 50 percent of patients admitted to a coronary care unit are shown subsequently to have myocardial infarction. Thus, a large number of the remaining patients could be transferred from the coronary care unit within 12 to 24 hours if one had available the results of serial analysis of plasma MBCK which would be cost-effective, psychologically pleasing to the patient and morally uplifting to a staff who are trained specifically to take care of acute infarction.

The WHO criteria are woefully inadequate, inappropriate and should be updated or discarded. If we examine the WHO criteria in detail, they state if there is chest pain plus an elevation of either SGOT, LDH or CK, the diagnosis of myocardial infarction is confirmed. This would be ludicrous in view of our present knowledge of the many causes of elevated plasma enzymes other than myocardial infarction. For example, a patient who has angina while at the same time is receiving intramuscular injections would be diagnosed as having acute myocardial infarction. This becomes even more ludicrous in diagnosing infarction in the postoperative patient in whom the enzymes are invariably diagnosing infarctionelevated, and should the patient have chest pain for whatever reason, would then be regarded as having myocardial infarction. This deficiency in the criteria reflects the fact that the criteria were founded before the introduction of diagnostic isoenzymes.

The electrocardiographic confirmation is confined to Q waves. Q waves are highly specific but relatively in sensitive. Today we know that about 20 to 40 percent of the patients admitted to the coronary care unit with documented myocardial infarction on the basis of serial elevations in CK or LDH isoenzymes do not exhibit Q waves on their electrocardiogram. The changes on the electrocardiogram are restricted to the ST-T segment which do not differ from those seen concomitant with angina in patients without myocardial necrosis. In addition, there are a multitude of causes for ST-T changes other than myocardial necrosis. Nevertheless, patients with non-Q wave infarction, as confirmed by elevated plasma MBCK, are at high risk for reinfarction and is a group in whom we can potentially do the most good with respect to prophylactic therapy and salvage of myocardium. Confirmation of myocardial necrosis in this group of patients, which in the past were in part probably referred to as coronary insufficiency or unstable angina, can be reliably determined with the use of plasma CK or LDH isoenzymes. The time has come, then, to be more precise and to put forth a diagnostic criterion in keeping with our present knowledge and present day practice.

In formulating guidelines for the diagnosis of myocardial infarction based on isoenzymes, one should emphasize frequent sampling and the need to analyze with sensitive and precise quantitative assays for C K and LDH isoenzymes. Patients admitted within 72 hours of onset of symptoms should have a blood sample collected on admission followed by one at least every six to eight hours for 24 hours. Samples should be analyzed for CK isoenzymes with a quantitative assay. The choice of assay and the values chosen for upper limit of normal would require considerable thought since standardization across different assays would be required. Based on our experience with over 200,000 assays comparing the radioimmunoassay with the glass bead method for MBCK, an upper limit of normal of 13 IU/L performed at 37°C has worked well. It becomes possible to improve your cardiac capacity with medications of My Canadian Pharmacy.

The specific criteria as to the extent and duration of elevation in plasma values required for the diagnosis of myocardial infarction would require some intense thought. The following guidelines with respect to the enzymatic criteria for plasma MBCK may serve as a working framework: 1) a serial elevation followed by a decrease in plasma MBCK to baseline levels with a change of 25 percent or more between any two values; 2) an increase in plasma MBCK activity of 50 percent or more between two samples separated by at least four hours and not more than 12 hours; 3) the diagnosis should preferably be made on not less than two samples in a 24-hour period separated by at least four hours; or 4) if only a single sample is present, diagnosis must be made on the basis of an elevation above normal by at least one-fold. Patients admitted beyond 72 hours from onset of infarction should preferably have LDH isoenzymes analyzed since MBCK may well have returned to normal. The other alternative, of course, would be to do pyrophosphate imaging. In the case of LDH isoenzymes, one may adopt a similar sampling frequency; however, analysis would most likely be semiquantitatively performed by densitometric scanning following separation by electrophoresis. The other approach is to use the immunoinhibition technique, but since one measures only LDH-1 and not LDH-2, it may be difficult to determine specificity with the immunoinhibition assay. In patients undergoing cardiac surgery, the diagnosis of myocardial infarction cannot be made on the basis of isoenzymes alone since MBCK and LDH-1 are consistently elevated from the surgical trauma to the heart. The development of new Q waves on the electrocardiogram is very specific, but highly insensitive. I would recommend pyrophosphate imaging which is most reliable if performed before and after cardiac surgery. In the case of noncardiac surgery, isoenzymes would provide a

very adequate diagnosis. In certain conditions, MBCK or LDH isoenzymes would be elevated due to release from skeletal muscle, and those exceptions would have to be excluded such as congenital muscular dystrophy. The inclusion of enzymes such as SGOT, HBD or SGPT simply adds to the cost and time required to make the diagnosis. The development of a uniform isoenzyme criterion for the diagnosis of myocardial infarction should decrease health care costs, improve patient care and reduce the often required rhetoric hypocrisy.