Myocardial scintigraphy in an emergency room Jan Lessem Heart section, Dept. of Medicine, General hospiital, MALMU, SWEDEN
Myocardial scintigraphy in the emergency room of the department of medicine, Malmo General hospital, was performed in 78 patients suspected of acute myocardial infarction. A mobile gamma camera (General Electric, USA) was used and 10 mCi 99mTcpyrophosphate (Diagnostics incorporated, USA) was injected intravenously. All investigations were carried out within ten hours after onset of symptoms. The earliest examinations were made in seven cases 4 hours post-onset of symptoms and in four cases 2 hours post-onset. All scintigrams were evaluated with regard to presence, localization, and the intensity of an uptake, and were read without knowledge of the clinical diagnosis. Each patient underwent a thorough clinical examination by a physician in charge of the emergency room. ECG and enzymes (SALAT and S-ASAT) were sampled twice with an interval of 6 hours. A pure clinical decision was then taken about the cause of the discomfort. When making his decision, the physician had no knowledge of the outcome of the scintigraphy. Three groups emerged: 1. Those believed clinically to have an acute myocardial infarction and therefore referred to the coronary care unit: 28 patients. 2. Those believed to have causes other than coronary disease for the chest pain and admitted to other wards in the department of medicine: 10 patients. 3. Those believed to have any underlying cardiac disorder causing their chest pain and thus were sent home: 40 patients. Those admitted to the coronary care unit or sent home were later re-examined scintigraphically with 1.5 mCi zOITI (Philips Duphar, the Netherlands) to detect any perfusion defects. Of the 28 patients admitted to the coro-
nary care unit, 23 had shown pyrophosphate uptake in the emergency room. Of these, 15 were well localized and showed an intensity exceeding 1.18 of the 23 also exhibited perfusion defects when re-examined and 17 of them were later discharged with a diagnosis of acute transmural myocardial infarction. 3 were discharged with the diagnosis unstable angina pectoris; the other 3 were discharged with the diagnosis other uhan cardiac. 5 patients, admitted to the coronary care unit, had exhibited negative pyrophosphate scintigrams in the emergency roam. None of these 5 later showed any perfusion defect. All were discharged with the diagnosis non-cardiac disorders. Of the 40 patients sent home, 26 had negative pyrophosphate examinations; 25 of them showed negative T1 when re-examined. The one patient with a T1 perfusion defect had suffered a previous apical infarct. However, 14 patients with positive pyrophosphate scintigrams were sent home. Intensity of the uptake in only one of the 14 exceeded one. This patient later developed an acute myocardial infarction. When the 14 patients were re-examined with 201Tl, it was found that 10 showed perfusion defects; the other 4 had no perfusion defects (Table I). From this study, it can be concluded that myocardial scintigraphy with BmTc-pyrophosphate yields positive results, before conventional laboratory methods, which in turn might lead to other therapy being started earlier. I t is then possible that more myocardium can be saved from final necrosis. Furthermore, a negative pyrophosphate scan in the emergency room would add to the clinical confidence in sending the patients home. However, a positive scintigram with an intensity above the lowest should be a warning and lead to admission to a coronary care unit.
121
Table I
This table shows the difference between scintigrapical results with both pyrophosphate and Thalliuni and discbarged diagnosis. Outcome of scintigraphy Positive pyrophosphate positive TI
Diagnoses when discharged 1 AM1 between examinations 2 old AM1 and aneurysm 4 unstable angina pectoris 3 chest pain of unknown origin
Positive pyrophosphate negative TI
3 unstable angina 1 chest pain of unknown origin
J . Fischer Hansen: What was the outcome of those patients who were sent home, but had a positive scintigraphy? Did they have an acute myocardial infarction?
1.Lessem: Usually 10-14 days after onset of symptoms. But at that late date, the intensity of the uptake is less than during the acute phase. If an aneurysm develops, a positive uptake might remain a long time after onset of symptoms.
/. Lessem: Of those sent home with a positive 99mTc-pyrophosphate scintigram, two later returned with verified acute myocardial infarcts. In six patients, we also found perfusion defects when re-examined with 201T1.The significance of this finding is not clear. I t indicates that a perfusion defect is present, but its age cannot be stated. Therefore we are still uncertain whether these patients had an i,nfarct when they came to the emergency room, but there is at least the suggestion that they might have had. The prognosis in this group of patients was unchanged. B. ScherstCn: What was the clinical advantage of the scintigrams? Could they be used as a prognostic tool?
1. Lessem: To
answer the first question: In our emergency ward study, a negative scintigram never gave a false result. Myocardial scintigraphy could possibly result in a more rational use of C C U beds. To answer the second question: Yes, to a certain extent, but our study was not planned as a true prognostic study.
P . F . Heilund-Carlsen: What is the latest time after an infarction when the Tc pyrophosphate scintigram can be expected still to be positive?
122
S . Persson: Would you wait 10 hours after the onset of symptoms to do a T c pyrophosphate scintigram?
/. Lessem: No. I n principle, patients with a negative scintigram can be sent home. E . Sandee: Is it possible from Tc pyrophosphate scintigraphy to decide whether a thoracic pain is a sign of impending myocardial infarction?
I . Lessem: I t is not possible to diagnose with either scintigraphy or any other method whether a true myocardial infarction will develop in these patients. B. W . /ohansson: What are the indications for myocardial scintigraphy in the emergency ward? Is negative scintigraphy with 201T1 or positive imaging with WmTcpyrophosphate preferable?
J Lessem: One indication could be to select more suitable patients for the coronary care units than has previously been done. However, myocardial scintigraphy should not be used alone in deciding the future of the patients, but should only be regarded as a compliment to other investigatory methods. I t is still uncertain whether ischae-
mic patients can be diagnosed with either Thallium or pyrophosphate in the emergency room, but if this is so, a more aggressive therapy might be instituted earlier. In the emergency room, it seems as though pyrophosphate is superior to Thallium: it cannot separate an old infarct from a new event. Re-infarcts can, for exemple, be very difficult to diagnose with Thallium.
Bengt W . Johansson: The ECG is often of minor help for the diagnosis of acute myocardial infarction in patients with an artificial pacemaker. Myocardial scintigraphy should be of assistance in these patients, provided the tissue reaction to the electrode does not induce false positive findings. Experiences from 10 pacemaker patients with’out any clinical or laboratory signs of acute infarction show no positive uptake with WmTc-pyrophosphate, indicating that myocardial imaging is of diagnostic value in these patients. Is determination of myoglobin in the urine or serum of diagnostic value in patients in the emergency ward or in patients seen by the doctor outside the hospital? Bengt Scherstln: The methods available today have not been sufficiently documented to defend their introduction in routine clinical work. Jan Lessem: A teststrip with a reaction based on the ability of myoglobin, excreted in urine, to act as a peroxidase has been tested in 62 patients with suspected acute myocardial infarction. Thirtyfive developed an infarot and the strip turned positive in only 18, of whom three were positive before ECG and enzyme rise. I n 27 patients with no myocardial infarction only two posiltive teststrips were found. The sensitivity of the strip was thus calculated to be 52 O/o, whereas specificity was found to be 93 O/O.
V . Hansteen: Most of the discussion has concerned scintigraphy and improved enzymatic diagnosis of acute infarction. Would it not be possible to get more information from the ECG? The ECG is highly
specific; it also provides a large amount of false negative findings. Is it possible to improve the diagnostic ECG sensitivity by using other leads, such as orthogonal Frank leads or vectorcardiography? J . Kjekshus: ECG is an empirical method, and we compare the ECG of a patient with ECG criteria considered to be normal. We will, of course, observe many false negative ECG. As yet, we still know too little about the ”forward problem” relating intracardiac events to the shape of the ECG to use it as a quantitative predictor. Because individual differences in the electrode distance and orientation to the infarct, differences in the geometry and conductivity of the chest, and variations in skin resistance, quantitative comparisons among patients are invalidated. The orthogonal leads compensate for some of these problems; this offers more sensitivity in the diagnosis. Vector loop analysis takes into consideration the spatial distribution of the electrocardiographic events and not only changes in peak amplitude of QRS waves. Especially by recording the vectorcardiograms sequentially during the evolution of an infarct, small changes are readily obtained. Furthermore, multiple recordings of the vectorcardiogram can be used to construct a curve rhat reflects the immediate development of the infarct. This could be of potential value in the future.
Bengt W . lobansson: What diagnostic criteria should we use in the diagnosis of acute myocardial infarction? Although differences exist between hospitals, I think many keep more or less strictly to the following criteria: 1. Central chest pain, pulmonary edema, syncope or shock. 2. Appearance of a pathological Q wave and/or appearance or disappearance of a localized ST elevation followed by a T wave invertion In two or more leads of a 12 lead ECG. 3. Two elevated ASAT values with a peak about 24 hours after onset of symptoms
123
in combination with a peak ALAT value about 36 hours after onset of symptoms and lower than the ASAT peak. Alternatively one elevated ASAT value in combination with one elevated LD value with a peak about three days after onset of symptoms. 4. Myocardial necrosis at autopsy of an age co:respcnding to the onset of symptoms. Criterion 4 or a combination of two of criteria 1, 2 and 3 are necessary for the diagnosis of acute myocardial infarction. Are we prepared today to revise or change these diagnostic criteria?
E . Lorentzen: As the S-CK peak is of shorter duration than that of S-ASAT, is it not reasonable to prefer S-ASAT? We still have little experience of the new methods. New sources of error still appear. This is true, for example, in the serial determination of S-CK for evaluation of infarct size (Editorial, Circulation 52: 1, 1975). I will therefore make a plea to wait to include these new metnods in the routine diagnosis of acute infarction until we have gained more experiences and well-founded results showing that they actually represent true progress.
S . Hofvendahl: We use the following routine. S-CK and S-CK-MB three times a day, S-ASAT and S-ALAT once a day, and S-LD once a day until maximal value has been passed. S-CK-MB and S-LD isoenzymes provide a cardiospecific enzyme combination that covers a maximum time interval. I n addition, S-ASAT and S-ALAT have a place in the diagnostic arsenal: they are well documented and not costly. They provide a simple estimate of the degree of possible liver involvement, which is of clinical value. Furthermore, it is possisble that microinfarctions are more readily diagnosed with the sensitive S-ASAT than with other methods.
C. Miiller: Is there any place for S-CKMB in the diagnosis of acute myocardial infarction during o r after cardiac surgery? Previous methods including enzymes are often unreliable. Is there a difference in the S-CK-MB response after an uncomplicated cardiotomy and a n aorto-coronary by-pass? Can an increase of S-CK-MB postoperatively be regarded as an expression of an acute myocardial infarction?
A . Pedersetr: Based on the enzyme findings in 1300 patients out of whom 900 had an acute myocardial infarction, our routine in Glostrup has included only S-CK-MB, unless there is reason to suspect that the infarction occurred more than 36 hours before the blood sample is taken. If so, we determine in addition S-ASAT, S-ALAT, and S-LD, and in selected cases an LD electrophoresis is done. S-CK-MB is analysed electrophoretically. The MB fraction can be completely isolated, znd the specificity is close to 100 O/o. This routine requires certain laboratory efforts, but the laboratory is also relieved of the other enzyme analyses, and the necessary costs are certainly lower than fcr myocardial scintigraphy.
124
S. Strom: Frequent CK-MB determinations in 25 consecutive cases of coronary by-pass operations with mammary artery or saphenous vein show that CK-MB in serum is found in all patients postoperatively with a wide range of maximum values. Myocardial infarction could not be diagnosed in any of these patients with conventional methods and the CK-MB curve postoperatively differs from that seen after an infarction with a maximum in direct connection to the operation. Drainage of the right atrium, which is routinely done during these operations, produces myocardial damage, but it is small and should be of the same magnitude in all patients. There is a correlation between CK-MB level and the duration of extracorporeal circulation and aortic clamping, that is to say, between enzyme release and the amount of ischaemia.
/. Lessem: Tc-pyrophosphate scintigraphy is of great value in the diagnosis of per- and postoperative myocardial infarction.
K . E . Grevin: Does S-CK and/or myoglobin increase in connection with a virus myositis and/or myocarditis? L. Malmberg: Enzymes were not checked routinely during the acute phase in our patients with viral myocarditis, but it is conceivable that myocardial necrosis produced by a myocarditis would cause a rise in SCK-MB. B . Scherstln: As far as I know, the literature contains no reports that give an unambiguous answer to this question. M. Herder: From a laboratory point of view, it would be advantageous if the clinicians used more strict criteria for the diagnosis of acute myocardial infarction as far as the enzymes CK, ASAT, ALAT, and LD are cmcerned, including standardized sampling times in relation to onset of symptoms. Ninety per cent of the nordic laboratories use the standardized nordic enzyme methods for analysis of these enzymes. G . Biorck: I have listened with interest to the questions and, as often happens, they have provoked some heretical thoughts in my mind. Is this refined diagnostics mainly a tart pour l'art, or does it really mean something to our decision making for the patient? Our Chairman and Doctor Scherstkn have both touched upon this matter, but being somewhat older, I may also have the privilege of being slightly more radical. What does it mean in practical terms to make a diagnosis of acute myocardial infarction in a patient? Any diagnosis carries with ilt a prognosis (or even two) one immediate, which may require instantaneous decisions and one long-term (if the patient survives), implying advice with regard to inode of life, employment, life insurance etc. - that is to say psychological loads. Therapy depends on prognosis: in selflimiting diseases with favourable prognosis therapy is often neither needed nor available, as in some dermatological diseases.
Now, what is the difference between therapy on the basis of symptomatology alone, or on the basis of diagnostics? The function of a diagnosis is to indicate a subpopulation among all who appear to have a relevant symptomatology - namely those who fit a set of more or less rigid criteria. I would estimate that the refined diagnostics presented here might increase the size of the subpopulation by a few per cent, perhaps from 95 to 99 per cent. But it is per se possible that the prognosis for the diagnostically selected subpopulation is comparable to the prognosis also for one or more other subpopulations who, for one or other reason, do not completely fit the criteria and thus fall outside the borders of the criteria. Now, it is conceivable that the assessment of the clinical symptomatology - for the experienced physician - might be as good a prognostic indication as that based on refined laboratory diagnostics. Could it therefore be of interest to organize further studies of the value of refined diagnostic procedures in a way, that might permit a comparison with the early clinical judgement, from the prognostic point of view? I would suggest that this possibility be given consideration in the lay-out of further studies. One reason why I urge you to consider this possibility is my feeling that while diagnosis and therapy have made great progress in recent decades, prognosis has advanced very little - as applied to the individual case. We have massive series of epidemiological and other statistical data, but we are still very much a t loss when judging the specific individual patient. I n our department, we have for some time engaged in a project of early, "clinical" prognostication in acute myocardial infarction by physicians and nurses in the CCU, and we hope that the experience derived from a comparison of our "bets" with the later verification by the patient's fate might help to improve our ability to make proper prognostic judgements.
125
Bengt W . Johansson: I t is often difficult to get a definite diagnosis in patients who die soon after the onset of symptoms. An autopsy might reveal a pulmonary embolus or a cerebral haemorrhage. An acute myocardial infarction takes several hours to produce clear-cut gross or microscopical changes. Half of the patients leaving hospital after treatment of an acute infarction die suddenly. This can be due to a ventricular fibrillation without an infarction; it can also be due to an acute infarction, and the
time might have been too short for a coronary thrombus to develop. The coronary circulation during ventricular fibrillation will drop to almost zero with subsequent myocardial changes. I t takes some time for the infarct to become manifest, although a decrease in potassium and an increase in sodium and calcium concentrations have been reported to occur a few minutes after the coronary circulation has stopped. These problems are especially relevant in forensic medicine.
The diagnostic of fresh ischaemic lesions in forensic pathology Gerhard E. Voigt Dept. of Forensic Medicine, University of Lund, LUND, SWEDEN
Sudden and unexpected death dominate the autopsy material of Departments of Forensic Medicine. Heart disease is the most common cause. By gross examination, it is difficult to differentiate such cases from intoxications with medicaments such as sleeping pills, tranquilizers, or analgetics, often in combination with alcohol. These intoxications d o not cause specific morphological changes and can easily be overlooked, as can an early myocardial infarction. To select the cases demanding toxicologic chemical analysis, it is most important to have methods to verify the early stages of myocardial ischaemia, indicating that the cause of death was cardiovascular. In our experience, the heart dissection technique during autopsy is important for visualizing early stages of infarction. Thus the left ventricle is opened by a cut a t the left margin of the heart running through the mitral valve. From this cut, another is made with scissors into the aorta, leaving a small part of the wall of the left ventricle between the two cuts. The wall of the left ventricle is then stretched open and its thickness is halved, beginning at the apex of the heart and continuing to the level of
126
the coronary sulcus. It is important not to wash the heart before investigating the cut curface. A fresh infarction has a prominent cut surface, but there is often no difference in the colour between the ischaemic and non-affected parts of the muscle. It is almost impossible to see fresh infarctions on small cut surfaces. Concerning further investigations to verify fresh myocardial infarction, Knight has recently surveyed reliable methods. H e recommends for the most part histochemical enzyme methods (malate dehydrogenase) and describes S D H and LDH as useful tests. For two reasons, we cannot use such methods as routine tests: 1) Many of our cases have a variable degree of autolysis making it impossible to obtain reliable results, 2) For a department with a large autopsy load (ZOO/year) and a small medical and technical staff, the histochemical methods are too time-consuming. Thus, we need simple methods that provide reliable results also on decomposed material. At our department, the Mallory P T A H stain has been chosen to visualize ischaemic myocardial lesions that can be overlooked
Myocardial scintigraphy in the emergency room of the department of medicine, Malmo General hospital, was performed in 78 patients suspected of acute myocardial infarction. A mobile gamma camera (General Electric, USA) was used and 10 mCi 99mTcpyrophosphate (Diagnostics incorporated, USA) was injected intravenously. All investigations were carried out within ten hours after onset of symptoms. The earliest examinations were made in seven cases 4 hours post-onset of symptoms and in four cases 2 hours post-onset. All scintigrams were evaluated with regard to presence, localization, and the intensity of an uptake, and were read without knowledge of the clinical diagnosis. Each patient underwent a thorough clinical examination by a physician in charge of the emergency room. ECG and enzymes (SALAT and S-ASAT) were sampled twice with an interval of 6 hours. A pure clinical decision was then taken about the cause of the discomfort. When making his decision, the physician had no knowledge of the outcome of the scintigraphy. Three groups emerged: 1. Those believed clinically to have an acute myocardial infarction and therefore referred to the coronary care unit: 28 patients. 2. Those believed to have causes other than coronary disease for the chest pain and admitted to other wards in the department of medicine: 10 patients. 3. Those believed to have any underlying cardiac disorder causing their chest pain and thus were sent home: 40 patients. Those admitted to the coronary care unit or sent home were later re-examined scintigraphically with 1.5 mCi zOITI (Philips Duphar, the Netherlands) to detect any perfusion defects. Of the 28 patients admitted to the coro-
nary care unit, 23 had shown pyrophosphate uptake in the emergency room. Of these, 15 were well localized and showed an intensity exceeding 1.18 of the 23 also exhibited perfusion defects when re-examined and 17 of them were later discharged with a diagnosis of acute transmural myocardial infarction. 3 were discharged with the diagnosis unstable angina pectoris; the other 3 were discharged with the diagnosis other uhan cardiac. 5 patients, admitted to the coronary care unit, had exhibited negative pyrophosphate scintigrams in the emergency roam. None of these 5 later showed any perfusion defect. All were discharged with the diagnosis non-cardiac disorders. Of the 40 patients sent home, 26 had negative pyrophosphate examinations; 25 of them showed negative T1 when re-examined. The one patient with a T1 perfusion defect had suffered a previous apical infarct. However, 14 patients with positive pyrophosphate scintigrams were sent home. Intensity of the uptake in only one of the 14 exceeded one. This patient later developed an acute myocardial infarction. When the 14 patients were re-examined with 201Tl, it was found that 10 showed perfusion defects; the other 4 had no perfusion defects (Table I). From this study, it can be concluded that myocardial scintigraphy with BmTc-pyrophosphate yields positive results, before conventional laboratory methods, which in turn might lead to other therapy being started earlier. I t is then possible that more myocardium can be saved from final necrosis. Furthermore, a negative pyrophosphate scan in the emergency room would add to the clinical confidence in sending the patients home. However, a positive scintigram with an intensity above the lowest should be a warning and lead to admission to a coronary care unit.
121
Table I
This table shows the difference between scintigrapical results with both pyrophosphate and Thalliuni and discbarged diagnosis. Outcome of scintigraphy Positive pyrophosphate positive TI
Diagnoses when discharged 1 AM1 between examinations 2 old AM1 and aneurysm 4 unstable angina pectoris 3 chest pain of unknown origin
Positive pyrophosphate negative TI
3 unstable angina 1 chest pain of unknown origin
J . Fischer Hansen: What was the outcome of those patients who were sent home, but had a positive scintigraphy? Did they have an acute myocardial infarction?
1.Lessem: Usually 10-14 days after onset of symptoms. But at that late date, the intensity of the uptake is less than during the acute phase. If an aneurysm develops, a positive uptake might remain a long time after onset of symptoms.
/. Lessem: Of those sent home with a positive 99mTc-pyrophosphate scintigram, two later returned with verified acute myocardial infarcts. In six patients, we also found perfusion defects when re-examined with 201T1.The significance of this finding is not clear. I t indicates that a perfusion defect is present, but its age cannot be stated. Therefore we are still uncertain whether these patients had an i,nfarct when they came to the emergency room, but there is at least the suggestion that they might have had. The prognosis in this group of patients was unchanged. B. ScherstCn: What was the clinical advantage of the scintigrams? Could they be used as a prognostic tool?
1. Lessem: To
answer the first question: In our emergency ward study, a negative scintigram never gave a false result. Myocardial scintigraphy could possibly result in a more rational use of C C U beds. To answer the second question: Yes, to a certain extent, but our study was not planned as a true prognostic study.
P . F . Heilund-Carlsen: What is the latest time after an infarction when the Tc pyrophosphate scintigram can be expected still to be positive?
122
S . Persson: Would you wait 10 hours after the onset of symptoms to do a T c pyrophosphate scintigram?
/. Lessem: No. I n principle, patients with a negative scintigram can be sent home. E . Sandee: Is it possible from Tc pyrophosphate scintigraphy to decide whether a thoracic pain is a sign of impending myocardial infarction?
I . Lessem: I t is not possible to diagnose with either scintigraphy or any other method whether a true myocardial infarction will develop in these patients. B. W . /ohansson: What are the indications for myocardial scintigraphy in the emergency ward? Is negative scintigraphy with 201T1 or positive imaging with WmTcpyrophosphate preferable?
J Lessem: One indication could be to select more suitable patients for the coronary care units than has previously been done. However, myocardial scintigraphy should not be used alone in deciding the future of the patients, but should only be regarded as a compliment to other investigatory methods. I t is still uncertain whether ischae-
mic patients can be diagnosed with either Thallium or pyrophosphate in the emergency room, but if this is so, a more aggressive therapy might be instituted earlier. In the emergency room, it seems as though pyrophosphate is superior to Thallium: it cannot separate an old infarct from a new event. Re-infarcts can, for exemple, be very difficult to diagnose with Thallium.
Bengt W . Johansson: The ECG is often of minor help for the diagnosis of acute myocardial infarction in patients with an artificial pacemaker. Myocardial scintigraphy should be of assistance in these patients, provided the tissue reaction to the electrode does not induce false positive findings. Experiences from 10 pacemaker patients with’out any clinical or laboratory signs of acute infarction show no positive uptake with WmTc-pyrophosphate, indicating that myocardial imaging is of diagnostic value in these patients. Is determination of myoglobin in the urine or serum of diagnostic value in patients in the emergency ward or in patients seen by the doctor outside the hospital? Bengt Scherstln: The methods available today have not been sufficiently documented to defend their introduction in routine clinical work. Jan Lessem: A teststrip with a reaction based on the ability of myoglobin, excreted in urine, to act as a peroxidase has been tested in 62 patients with suspected acute myocardial infarction. Thirtyfive developed an infarot and the strip turned positive in only 18, of whom three were positive before ECG and enzyme rise. I n 27 patients with no myocardial infarction only two posiltive teststrips were found. The sensitivity of the strip was thus calculated to be 52 O/o, whereas specificity was found to be 93 O/O.
V . Hansteen: Most of the discussion has concerned scintigraphy and improved enzymatic diagnosis of acute infarction. Would it not be possible to get more information from the ECG? The ECG is highly
specific; it also provides a large amount of false negative findings. Is it possible to improve the diagnostic ECG sensitivity by using other leads, such as orthogonal Frank leads or vectorcardiography? J . Kjekshus: ECG is an empirical method, and we compare the ECG of a patient with ECG criteria considered to be normal. We will, of course, observe many false negative ECG. As yet, we still know too little about the ”forward problem” relating intracardiac events to the shape of the ECG to use it as a quantitative predictor. Because individual differences in the electrode distance and orientation to the infarct, differences in the geometry and conductivity of the chest, and variations in skin resistance, quantitative comparisons among patients are invalidated. The orthogonal leads compensate for some of these problems; this offers more sensitivity in the diagnosis. Vector loop analysis takes into consideration the spatial distribution of the electrocardiographic events and not only changes in peak amplitude of QRS waves. Especially by recording the vectorcardiograms sequentially during the evolution of an infarct, small changes are readily obtained. Furthermore, multiple recordings of the vectorcardiogram can be used to construct a curve rhat reflects the immediate development of the infarct. This could be of potential value in the future.
Bengt W . lobansson: What diagnostic criteria should we use in the diagnosis of acute myocardial infarction? Although differences exist between hospitals, I think many keep more or less strictly to the following criteria: 1. Central chest pain, pulmonary edema, syncope or shock. 2. Appearance of a pathological Q wave and/or appearance or disappearance of a localized ST elevation followed by a T wave invertion In two or more leads of a 12 lead ECG. 3. Two elevated ASAT values with a peak about 24 hours after onset of symptoms
123
in combination with a peak ALAT value about 36 hours after onset of symptoms and lower than the ASAT peak. Alternatively one elevated ASAT value in combination with one elevated LD value with a peak about three days after onset of symptoms. 4. Myocardial necrosis at autopsy of an age co:respcnding to the onset of symptoms. Criterion 4 or a combination of two of criteria 1, 2 and 3 are necessary for the diagnosis of acute myocardial infarction. Are we prepared today to revise or change these diagnostic criteria?
E . Lorentzen: As the S-CK peak is of shorter duration than that of S-ASAT, is it not reasonable to prefer S-ASAT? We still have little experience of the new methods. New sources of error still appear. This is true, for example, in the serial determination of S-CK for evaluation of infarct size (Editorial, Circulation 52: 1, 1975). I will therefore make a plea to wait to include these new metnods in the routine diagnosis of acute infarction until we have gained more experiences and well-founded results showing that they actually represent true progress.
S . Hofvendahl: We use the following routine. S-CK and S-CK-MB three times a day, S-ASAT and S-ALAT once a day, and S-LD once a day until maximal value has been passed. S-CK-MB and S-LD isoenzymes provide a cardiospecific enzyme combination that covers a maximum time interval. I n addition, S-ASAT and S-ALAT have a place in the diagnostic arsenal: they are well documented and not costly. They provide a simple estimate of the degree of possible liver involvement, which is of clinical value. Furthermore, it is possisble that microinfarctions are more readily diagnosed with the sensitive S-ASAT than with other methods.
C. Miiller: Is there any place for S-CKMB in the diagnosis of acute myocardial infarction during o r after cardiac surgery? Previous methods including enzymes are often unreliable. Is there a difference in the S-CK-MB response after an uncomplicated cardiotomy and a n aorto-coronary by-pass? Can an increase of S-CK-MB postoperatively be regarded as an expression of an acute myocardial infarction?
A . Pedersetr: Based on the enzyme findings in 1300 patients out of whom 900 had an acute myocardial infarction, our routine in Glostrup has included only S-CK-MB, unless there is reason to suspect that the infarction occurred more than 36 hours before the blood sample is taken. If so, we determine in addition S-ASAT, S-ALAT, and S-LD, and in selected cases an LD electrophoresis is done. S-CK-MB is analysed electrophoretically. The MB fraction can be completely isolated, znd the specificity is close to 100 O/o. This routine requires certain laboratory efforts, but the laboratory is also relieved of the other enzyme analyses, and the necessary costs are certainly lower than fcr myocardial scintigraphy.
124
S. Strom: Frequent CK-MB determinations in 25 consecutive cases of coronary by-pass operations with mammary artery or saphenous vein show that CK-MB in serum is found in all patients postoperatively with a wide range of maximum values. Myocardial infarction could not be diagnosed in any of these patients with conventional methods and the CK-MB curve postoperatively differs from that seen after an infarction with a maximum in direct connection to the operation. Drainage of the right atrium, which is routinely done during these operations, produces myocardial damage, but it is small and should be of the same magnitude in all patients. There is a correlation between CK-MB level and the duration of extracorporeal circulation and aortic clamping, that is to say, between enzyme release and the amount of ischaemia.
/. Lessem: Tc-pyrophosphate scintigraphy is of great value in the diagnosis of per- and postoperative myocardial infarction.
K . E . Grevin: Does S-CK and/or myoglobin increase in connection with a virus myositis and/or myocarditis? L. Malmberg: Enzymes were not checked routinely during the acute phase in our patients with viral myocarditis, but it is conceivable that myocardial necrosis produced by a myocarditis would cause a rise in SCK-MB. B . Scherstln: As far as I know, the literature contains no reports that give an unambiguous answer to this question. M. Herder: From a laboratory point of view, it would be advantageous if the clinicians used more strict criteria for the diagnosis of acute myocardial infarction as far as the enzymes CK, ASAT, ALAT, and LD are cmcerned, including standardized sampling times in relation to onset of symptoms. Ninety per cent of the nordic laboratories use the standardized nordic enzyme methods for analysis of these enzymes. G . Biorck: I have listened with interest to the questions and, as often happens, they have provoked some heretical thoughts in my mind. Is this refined diagnostics mainly a tart pour l'art, or does it really mean something to our decision making for the patient? Our Chairman and Doctor Scherstkn have both touched upon this matter, but being somewhat older, I may also have the privilege of being slightly more radical. What does it mean in practical terms to make a diagnosis of acute myocardial infarction in a patient? Any diagnosis carries with ilt a prognosis (or even two) one immediate, which may require instantaneous decisions and one long-term (if the patient survives), implying advice with regard to inode of life, employment, life insurance etc. - that is to say psychological loads. Therapy depends on prognosis: in selflimiting diseases with favourable prognosis therapy is often neither needed nor available, as in some dermatological diseases.
Now, what is the difference between therapy on the basis of symptomatology alone, or on the basis of diagnostics? The function of a diagnosis is to indicate a subpopulation among all who appear to have a relevant symptomatology - namely those who fit a set of more or less rigid criteria. I would estimate that the refined diagnostics presented here might increase the size of the subpopulation by a few per cent, perhaps from 95 to 99 per cent. But it is per se possible that the prognosis for the diagnostically selected subpopulation is comparable to the prognosis also for one or more other subpopulations who, for one or other reason, do not completely fit the criteria and thus fall outside the borders of the criteria. Now, it is conceivable that the assessment of the clinical symptomatology - for the experienced physician - might be as good a prognostic indication as that based on refined laboratory diagnostics. Could it therefore be of interest to organize further studies of the value of refined diagnostic procedures in a way, that might permit a comparison with the early clinical judgement, from the prognostic point of view? I would suggest that this possibility be given consideration in the lay-out of further studies. One reason why I urge you to consider this possibility is my feeling that while diagnosis and therapy have made great progress in recent decades, prognosis has advanced very little - as applied to the individual case. We have massive series of epidemiological and other statistical data, but we are still very much a t loss when judging the specific individual patient. I n our department, we have for some time engaged in a project of early, "clinical" prognostication in acute myocardial infarction by physicians and nurses in the CCU, and we hope that the experience derived from a comparison of our "bets" with the later verification by the patient's fate might help to improve our ability to make proper prognostic judgements.
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Bengt W . Johansson: I t is often difficult to get a definite diagnosis in patients who die soon after the onset of symptoms. An autopsy might reveal a pulmonary embolus or a cerebral haemorrhage. An acute myocardial infarction takes several hours to produce clear-cut gross or microscopical changes. Half of the patients leaving hospital after treatment of an acute infarction die suddenly. This can be due to a ventricular fibrillation without an infarction; it can also be due to an acute infarction, and the
time might have been too short for a coronary thrombus to develop. The coronary circulation during ventricular fibrillation will drop to almost zero with subsequent myocardial changes. I t takes some time for the infarct to become manifest, although a decrease in potassium and an increase in sodium and calcium concentrations have been reported to occur a few minutes after the coronary circulation has stopped. These problems are especially relevant in forensic medicine.
The diagnostic of fresh ischaemic lesions in forensic pathology Gerhard E. Voigt Dept. of Forensic Medicine, University of Lund, LUND, SWEDEN
Sudden and unexpected death dominate the autopsy material of Departments of Forensic Medicine. Heart disease is the most common cause. By gross examination, it is difficult to differentiate such cases from intoxications with medicaments such as sleeping pills, tranquilizers, or analgetics, often in combination with alcohol. These intoxications d o not cause specific morphological changes and can easily be overlooked, as can an early myocardial infarction. To select the cases demanding toxicologic chemical analysis, it is most important to have methods to verify the early stages of myocardial ischaemia, indicating that the cause of death was cardiovascular. In our experience, the heart dissection technique during autopsy is important for visualizing early stages of infarction. Thus the left ventricle is opened by a cut a t the left margin of the heart running through the mitral valve. From this cut, another is made with scissors into the aorta, leaving a small part of the wall of the left ventricle between the two cuts. The wall of the left ventricle is then stretched open and its thickness is halved, beginning at the apex of the heart and continuing to the level of
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the coronary sulcus. It is important not to wash the heart before investigating the cut curface. A fresh infarction has a prominent cut surface, but there is often no difference in the colour between the ischaemic and non-affected parts of the muscle. It is almost impossible to see fresh infarctions on small cut surfaces. Concerning further investigations to verify fresh myocardial infarction, Knight has recently surveyed reliable methods. H e recommends for the most part histochemical enzyme methods (malate dehydrogenase) and describes S D H and LDH as useful tests. For two reasons, we cannot use such methods as routine tests: 1) Many of our cases have a variable degree of autolysis making it impossible to obtain reliable results, 2) For a department with a large autopsy load (ZOO/year) and a small medical and technical staff, the histochemical methods are too time-consuming. Thus, we need simple methods that provide reliable results also on decomposed material. At our department, the Mallory P T A H stain has been chosen to visualize ischaemic myocardial lesions that can be overlooked
