Radionuclides in acute myocardial infarction

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<ul><li><p>Radionuclides in acute myocardial infarction </p><p>Jan Lessem </p><p>Heart section, Dept. of Medicine, General Hospital, MALMU, SWEDEN </p><p>The history of cardiovascular nuclear medi- cine is intimately related to the develop- ment of nuclear medicine and to the desire of cardiologists to find procedures less trau- matic than catheterizations (4, 39). These factors combined with difficulties of diag- nosing ischaemic heart diseases in some pa- </p><p>tients, due to previous pathological ECG and equivocal enzyme response, led to the use of radionuclide methods in this group of patients. Most patients with suspected acute myocardial infarction are usually im- mobile during the first phase of their disease and are monitored in a coronary care unit. </p><p>Fig . 1. A mobile gammacamera - Portacamera I ! c (General Electric). Bedside examination i s shown. </p><p>27 </p></li><li><p>Radionuclide methods were not available to the cardiologist, despite the development of better radiopharmaceuticals, until the recent development of the mobile gamma camera (fig. 1). This brought bedside nuclear medi- cine into the coronary care unit (45). </p><p>The employment of radionuclide methods in the diagnosis and evaluation of patients with acute myocardial infarction followed mainly three directions (Table I): </p><p>Table I Methods used In cardlovascular nuclear medlclne I . Positive infarct scintigraphy - substan- </p><p>ces accumulating in necrotic myocar- dium: 203Hg- Mercurascan 67Ga 99mTc-pyrophosphate WmTc-tetrac ycline WmTc-glucoheptonate </p><p>2. Negative infarct scintigraphy - sub- stances accumulating in normal myocar- dium 43K 86Rb 131cs </p><p>129cs zolTl 13NH4 + 54Mn llC-Palmitic acid </p><p>ments WmTc-human serum albumin WmTc-erythrocytes </p><p>1) Positive infarct scintigraphy, with sub- stances accumulating in infarcted myo- cardium. Among the first substances des- cribed were mercury isotopes, such as 203Hg tagged to hydroxymercuryfluores- cein (33) which gave satisfactory results in dogs with induced acute infarct (18, 25, 42); these never succeeded clinically. </p><p>Recently, a different group of sub- stances, mainly phosphates labelled with WmTc, were shown to be clinically appli- cable in the diagnosis of acute myocar- dial infarction. Bonte and coworkers (6) </p><p>3. Radiocardiography - hernodynamic asses- </p><p>showed that a pyrophosphate labelleled with 99mTc accumulated in acutely in- farcted myocardium. Later others veri- fied this (16, 28, 35, 56). 9 9 m T c pyro- phosphate proved exrrcmely useful in diagnosing peri- and postoperative myo- cardial infarctions (32, 41); in this clini- cal setting, enzymes and ECG cannot be used after cardiac surgery. </p><p>99mTc, obtained as a daughter product of WMo, has a half-life of 6 hours and gamma ray energy of 147 keV. Thus it is suitable for the low energy mobile gam- ma cameras. </p><p>The mechanism behind the pyrophos- phate uptake is obscure, but it has been postulated that pyrophosphate has an af- finity to hydroxyapatite crystals formed in the mitochondria when the myocar- dial cells undergo necrosis (8, 49, 50). Several groups (12, 20, 48) recently pre- sented evidence that pyrophosphate is taken up mainly by irreversibly dam- aged myocardial cells. These might still have some perfusion left (55) thus enab- ling pyrophosphate to reach them. </p><p>Simultaneously with the development of 99mTc-pyrophosphate, other agents, such as WmTc-tetracycline (23, 24) and later WmTc-glucoheptonate (26), were introduced as infarct labelling agents. However, both these substances have largely been abandoned, as the interval between injection of the radionuclide and the imaging procedure was too long, allowing other parameters to provide the diagnosis. Negative infarct scintigraphy using substances accumulating in normal myo- cardium. These radionuclides are belie- ved to reflect regional myocardial per- fusion, and when the perfusion is decrea- sed, a perfusion defect appears in the scintigram. The substances in this group are potassium-43 (57) and its analogues. Several have been used, such as 86Rb (11), I3lCs (4, 12), and lZ9Cs (44). All of them had a gamma energy level more suitable for the rectilinear scanner than for the gamma camera; thus their clini- </p><p>28 </p></li><li><p>cal applicability was limited. Recently, another potassium analogue, 201T1, was introduced (27) and proved to be a very useful tool in the diagnosis of acute myo- cardial infarction (19, 52, 54). I t has two energy levels, (80 and 167 keV), both being ideal for the low energy mo- bile gamma cameras. The long half-life (about 72 hours) eliminates the disad- vantage of being a cyclotron produced product. </p><p>The potassium analogues reflect the function of the sodium-potassium pump within the myocardial cells. When the myocardium is perfused, a significant amount of potassium is withheld intra- cellularly. If the perfusion is decreased, the amount of available potassium is also decreased; thus a perfusion defect in the scintigram will appear. From this, it is apparent that no differentiation of the age of the perfusion defect is possib- le with these radionuclides. </p><p>720 - </p><p>640 - </p><p>576 - </p><p>504 - </p><p>432 - </p><p>360 - </p><p>288 - </p><p>216 - </p><p>144 - 72 - </p><p>Maseri and coworkers (34) showed that potassium or its analogues are lar- gely extracted by the myocardium dur- ing the first circulatory pass, and when evenly mixed with the blood, are distri- buted proportionally to the cardiac out- put (46). </p><p>3) Radiocardiography, where the left ventricular function and wall motion are studied. Ventricular function can be measured non-invasively by two me- thods: First by recording the initial pas- sage of a bolus injected blood pool tra- cer through the heart, first Fass study, which Ashburn and Schelbert utilized (47). The first pass method utilizes a recording of the time-activity curve over the left ventricle that has peaks and val- leys corresponding to end-diastole and end-systole (Fig. 2) . </p><p>Second by data recording after the tracer has equilibrated. An ECG-gate and the scintillation camera is used so that images </p><p>0 </p><p>Fig. 2. A first passage curve is exemplified. The ejection fraction in this patient was calculated to be 41 010. </p><p>29 </p></li><li><p>Several studies, independent (17) of each other, have shown (17, 51) correlation coef- ficients of 0.9 or better for ejection fractions obtained with radionuclide methods and an- giography (37). </p><p>Impaired left ventricular function can then be diagnosed. Left ventricular wall mo- tion is best studied with gated blood pool studies, where diagnosis of akinetic and dyskinetic areas can easily be made. </p><p>Both methods have the advantage of ac- cumolating data over a relatively short time. This allows them to be used rather easily in the coronary care unit. They can very easily be repeated several times during the patients stay in the ward, and thereby yield information of his day to day henio- dynamic situation. It seems as though both methods, properly utilized, can predict left ventricular failure early (15, 51) and also estimate the effect of treatment. </p><p>The indications for using radionuclide methods in cardiology are several and have been demonstrated by several reports. The following seem to be the major indications: 2) Differentiation of origin of chest pain </p><p>(47) b) Previous pathological ECG, e.g., bundle </p><p>branch block, remaining ST-T changes after previous infarcts in combination with chest pain postoperatively </p><p>c) Differentiation bctween new and old in- farcts (54) </p><p>d) No adequate enzyme response, e.g., al- coholism, liver pathology, postoperati- vely </p><p>e) Hemodynamic assebsement of the work- ing capacity of the right and left ven- tricles during several phases of the in- farct </p><p>Besides these, several reports by Botvinick and coworkers have shown that sizing of infarcted myocardium can be performed with WmTc-pyrophosphate (7). Holman and coworkers recently confirmed these findings (22). These results suggest that in the future it will be possible to judge the efficiency of decreasing the size of a necrotic area by pharmacological or surgical interventions. </p><p>F i g . 3. After injection of 15 mCi 99~nTc-human serum albumin, a gated study was performed in this patient. The upper panel illustrates end- systole and the bottom panel illustrates end- diastole. N o akinetic area can be recognized. </p><p>are recorded during end-systole and end- diastole (40, 43) (Fig. 3). Gated studies have the advantage of being able to use several views after a single tracer injection, and are therefore more like regular angio- graphy. Both methods can be used to cal- culate the left ventricular ejection fraction, according to the following formula: LVEF = EDV - ESV/EDV - BKG, </p><p>where </p><p>fraction LVEF = left ventricular ejection </p><p>EDV = end-diastole volume ESV = end-systolic volume BKG = background </p><p>30 </p></li><li><p>These techniques make possible early diagnosis of acute myocardial infarction (29). Willerson and coworkers found posi- tive pyrophosphate scintigrams already 12 hours after the onset of symptoms; Wackers et a1 found that perfusion defects with 20*T1 could be diagnosed as early as 6 hours after the cnset of symptoms. In Wackers series all patients examined before 6 hours after the onset had developed perfusion de- fects in areas later corresponding to ECG- localization of the infarct (54). </p><p>Cllnlcal study All these methods were used in patients ad- mitted to the coronary care unit of the Malmo General hospital with primary cli- nical suspicion of acute myocardial infarc- tion due to severe chest pain, pulmonary oedema, dysrythmias, and dyspnea. </p><p>The clinical diagnosis of acute myocar- dial infarction was based on any of the following criteria: </p><p>Subjective symptoms in combination with typical QRST-changes in the ECG Subjective symptoms in combination with two elevated enzyme values (S- </p><p>Typical QRST-changes in the ECG in combination with two elevated enzyme values Autopsy data (21, 28). </p><p>ASAT, S-LD) </p><p>In contrast, the diagnosis of unstable an- gina pectoris was based on a combination of the following criteria: </p><p>Previous stable angina, or angina of re- cent onset with progresive increase in severity of symptoms Angina at rest with recurrent episodes lasting more than 20 minutes and poor- ly relieved by nitrates No elevation of serum enzymes Transient ST-T changes that frequently return to normal after the attack (10, 4). </p><p>All 350 patients were examined with 10 mCi NmTc-pyrophosphate (Byk-Mallin- crodt, USA, Solcoscint, Kabi-Diagnostica, </p><p>Diagnostics inc., USA); 125 patients were also investigated with 1.5 mCi 201Tl (Phi- lips Duphar, the Netherlands). In 48 pa- tients, different hemodynamic evaluations were also made. A mobile gamma camera, Portacamera I1 B or C (General Electric, USA) was used with a standard low-energy parallel hole colimator. The scintigrams were obtained in anterior - posterior, left 30 anterior oblique and left lateral positions. All were evaluated for presence, absence, size, localization, and intensity of an uptake or a defect. When radiocardiography was performed, the left ventricular ejection frac- tion was counted; if a gated study was un- dertaken, the wall motion was estimated. </p><p>Results </p><p>Of the 350 pyrophosphate examinations, 264 showed positive uptakes (Table 11). In the group of 188 patients with acute trans- mural infarction, 180 showed radionuclide accumulation and well localized intense up- takes in 90 per cent. (Fig. 4). The correla- </p><p>Fig . 4 . Myocardial rcintigram with 99mTc-py- rophosphate, recorded 90 minutes after injec- tion, in LAO 30 position. An anterior grade 3 intense uptake was recorded in the patient with a transmural anterior infarct. The record- ing was made with the Portacamera II c. </p><p>31 </p></li><li><p>tion between the uptake localization and ECG localization of the infarct was excel- lent. All 5 patients with left bundle branch block, but who fulfilled the criteria for acute myocardial infarcion also exhibited well localized and intense pyrophosphate uptakes. The earliest uptake was registered in 10 patients examined 4 hours after the onset of symptoms. </p><p>Of the patients diagnosed as unstable an- gina pectoris, 73 per cent showed an uptake; but this was distinctly different lrom the uptake in transmural infarcts, which also Abr'ulla and coworkers found ( I ) . These patients had low graded, diffusely spread uptakes (Fig. 5 ) . </p><p>F i g , 6 . A huge antero-lateral uptake with the intensity graded 3. The patient suffered f rom Chagas disease. The scintigram mimicked the pattern of transmural myocardial infarction. </p><p>Fig . I. A 42-year old male with a diffuse low intense pyrophosphate uptake seen in combina- tion with unstable angina pectoris. </p><p>Positive uptakes were found in five pa- tients with other cardiac diseases. One had Chagas disease (30) (Fig. 6 ) , and one, Prinz- metal variant angina. Two were found in patients with old infarcts and ventricular aneurysms, which al.so Ahmad (2) observed. The final positive pyrophosphate scinti- grams were registered in a patient who de- veloped an acute myocardial infarction after defibrillation (Fig. 7), a finding previously reported by diCola and coworkers (14). </p><p>Fig. 7 . A pyrophosphate uptake recorded in a patient after transthoracic counter current schock. </p><p>125 patients were also examined with Zo1T1. A very good correlation existed bet- ween a thallium defect and a pyrophos- phate uptake (Fig. 8). However, seven TI- scintigrams showed perfusion defects where no new infarct could be verified in patients who had previously sustained infarcts. </p><p>32 </p></li><li><p>separate them from those with acute myo- cardial infarction. A similar finding was recently reported by Wackers and cowork- ers (53). No false negative has been repor- ted with 201Tl-scintigraphy. </p><p>Gated thallium studies have also been per- formed with a pin hole collimator (focus- ing on the septum) which has been utilized when septal infarcts or conduction disorders were present (Fig. 10). </p><p>Fig . 8. An LAO 4 1 O recording with 201T1, in a pctient with an inferior transmural infarct. In the apical area a large perfusion defect is seen. The recording was made with Portacamera 11 c 20 minutes after injection. </p><p>In six of them the pyrophosphate exami- nation remained negative and in one it was questionably positive, probably owing to a ventricular aneurysm. Five patients with unstable angina pectoris had perfusion de- fects (Fig. 9) thus making it impossible to </p><p>Fig. 10. A gated 2olTl-study performed with a pin hole collimator in a patient with a left bundle branch block. The upper panel illustra- tes end-systole and the lower end-diastole. In the lower panel, a perfusion defect is seen in the septal region. </p><p>Consl usions I t can be concluded that both 99mTc-pyro- phosphate and 201T1 are useful aids in the diagnosis of acute myocardial infarction, as Parkey and several others have shown (29, 38, 5). Both methods have a high degree of </p><p>Fig . 9. The LAO 4 j 0 recording with 201T1, in a patient with unstable angina. Note the decrea- sed perfusion in the antero-spetal region. </p><p>33 </p></li><li><p>sensitivity and specificity and rarely sho...</p></li></ul>