Technetium-99m antimyosin antibody (3-48) myocardial imaging: human biodistribution, safety and clinical results in detection of acute myocardial infarction.

Technetium-99m antimyosin (99mTc-AM) antibody imaging may have significant advantages over indium-111 antimyosin in clinical practice. The purpose of this study was to determine the human biodistribution, the safety profile and the sensitivity of 99mTc-AM (3-48) imaging in the detection of both Q-wave and non-Q-wave myocardial infarction (MI). Biodistribution and safety parameters were mainly determined in 12 normal healthy volunteers while 40 patients with proven MI (22 Q-wave, 18 non-Q-wave) were injected with 99mTc-AM (20-25 mCi) between 5 h and 7 days after the onset of acute chest pain. Three standard planar views were performed at 6 h and at 24 h post injection. Both sets of images were completed in 33 patients while two patients were imaged only at 6 h, three patients only at 18 h and one at 18 and 24 h. One patient was not imaged. Vital signs and ECG were recorded and blood samples for haematology, biochemistry and human antimurine antibodies (HAMA) and urinalysis were obtained in all volunteers and patients. No serious adverse reactions or side-effects attributable to 99mTc-AM have been reported. No volunteers or patients developed allergic reactions or significant increases in HAMA titres. Reading of 99mTc-AM imaging was performed by two blinded experienced observers. The sensitivity of 99mTc-AM in the detection of MI was 100% (21/21) for Q-wave and 83.3% (15/18) for non-Q-wave infarctions. The overall sensitivity was 92.3% (36/39). The three false-negative cases were inferoposterior MI. A certain degree of uptake focalization was seen in 26 out of 35 (74.2%) at 6 h. At 24 h, two patients (5.8%) did not show 99mTc-AM uptake while 22 (64.7%) showed intense focal uptake, seven (20.6%) moderate uptake and 3 (8.9%) slight uptake. It is concluded that 99mTc-AM (3-48) imaging is safe and shows high sensitivity in the detection of both Q-wave and non-Q-wave MI even with early imaging (6 h post injection). These promising results warrant further clinical investigation.

Effect of amlodipine, atenolol and their combination on myocardial ischemia during treadmill exercise and ambulatory monitoring. Canadian Amlodipine/Atenolol in Silent Ischemia Study (CASIS) Investigators.

OBJECTIVES: This study compared the effects of amlodipine, atenolol and their combination on ischemia during treadmill testing and 48-h ambulatory monitoring. BACKGROUND: It is not known whether anti-ischemic drugs exert similar effects on ischemia during ambulatory monitoring and exercise treadmill testing. METHODS: Patients with stable coronary artery disease and ischemia during treadmill testing and ambulatory monitoring were randomized to receive amlodipine (n = 51) or atenolol (n = 49). Each group underwent a counterbalanced, crossover evaluation of single drug and placebo, followed by evaluation of the combination. RESULTS: Amlodipine and the combination prolonged exercise time to 0.1-mV ST segment depression by 29% and 34%, respectively (p < 0.001) versus 3% for atenolol (p = NS). During ambulatory monitoring, the frequency of ischemic episodes decreased by 28% with amlodipine (p = 0.083 [NS]), by 57% with atenolol (p < 0.001) and by 72% with the combination (p < 0.05 vs. both single drugs; p < 0.001 vs. placebo). Suppression of ischemia during exercise testing and ambulatory monitoring was similar in patients with and without exercise-induced angina. Exercise time to angina improved by 29% with amlodipine (p < 0.01), by 16% with atenolol (p < 0.05) and by 39% with the combination (p < 0.005 vs. placebo, atenolol and amlodipine). In patients with angina, total exercise time improved by 16% with amlodipine (p < 0.001), by 4% with atenolol (p = NS) and by 19% with the combination (p < 0.05 vs. placebo and either single drug). In those patients without angina, no therapy significantly improved total exercise time. CONCLUSIONS: Ischemia during treadmill testing was more effectively suppressed by amlodipine, whereas ischemia during ambulatory monitoring was more effectively suppressed by atenolol. The combination was more effective than either single drug in both settings.

Myocardial technetium 99m-labeled sestamibi single-photon emission computed tomographic imaging in the detection of coronary artery disease: comparison between early (15 minutes) and delayed (60 minutes) imaging.

BACKGROUND: Previous studies have demonstrated that there is a "partial" myocardial redistribution of 99mTc-labeled sestamibi (MIBI) between 1 and 3 hours after intravenous injection at stress. The purpose of this prospective study was to compare MIBI single-photon emission computed tomographic (SPECT) imaging performed 15 and 60 minutes after the injection at stress in the detection of coronary artery disease. METHODS AND RESULTS: Thirty-five patients with coronary artery disease (26 underwent coronary angiography and 23 had a positive 201Tl study result) were included in this study. SPECT imaging started 15 minutes after the injection of 25 to 30 mCi MIBI at peak stress (180-degree arc, 32 angles, 25 sec/view, and high-resolution collimator). Patients underwent reimaging at 60 minutes according to the same protocol and with the same gamma camera. A rest study was obtained 75 minutes after the injection of MIBI (25 to 30 mCi) at rest, 48 hours later. Images (divided for a total of 19 segments per patient) were interpreted by two blinded observers for patient diagnosis and segmental comparison. The patient diagnosis was the same for the two protocols: normal = 3, ischemia = 27, and scar = 5. The segmental agreement (kappa = 0.90) was 632/665 (95.0%). The imaging performed at 15 minutes detected normal, ischemia, and scar in 413, 189, and 63 segments, respectively, whereas the imaging performed at 60 minutes detected 422, 180, and 63 segments, respectively (difference not significant). The early and delayed images were placed side by side for subjective comparison of the extent of the defect. Early imaging showed slightly larger defects in six patients, equal defects in 24 patients, and slightly smaller defects in five patients. Ischemic/normal wall ratios were 0.67 +/- 0.16 at 15 minutes and 0.68 +/- 0.15 at 60 minutes. CONCLUSIONS: There is no clinically significant difference between SPECT imaging performed at 15 minutes or 60 minutes after the injection of MIBI at stress. Furthermore, this study showed that it is feasible to obtain good-quality MIBI images even 15 minutes after the injection at stress.

Relative importance of psychologic traits and severity of ischemia in causing angina during treadmill exercise. Canadian Amlodipine/Atenolol in Silent Ischemia Study (CASIS) Investigators.

OBJECTIVES: This study was conducted to compare the influence of psychologic traits versus ischemia severity on the occurrence of angina during treadmill exercise. BACKGROUND: Some studies suggest that angina is associated with certain psychologic traits, whereas others show an association with more severe ischemia. The relative influence of these two factors and the extent to which they interact are not known. METHODS: Off-drug treadmill exercise testing and a battery of psychologic tests were performed on 122 patients with known coronary artery disease. Psychologic tests measured sensitivity to physical symptoms, denial and deception, type A behavior, anger, hostility, depression, marital adjustment and amount of external stress. Stepwise logistic regression was used to determine the independent association of psychologic traits, ischemic threshold and exercise tolerance with the occurrence of angina. RESULTS: Angina during treadmill exercise was reported by 66 of 122 patients. On univariate testing, angina was positively associated with sensitivity to physical symptoms (p < 0.001), type A behavior (p = 0.021) and depression (p = 0.032) and was negatively associated with exercise tolerance (p < 0.001) and work load threshold for ischemia (p < 0.01). Multivariate analysis revealed independent and additive associations of angina with sensitivity to physical symptoms (p = 0.003), exercise capacity (p = 0.003) and work load threshold for ischemia (p = 0.018). Once these were included in a logistic model, depression and type A behavior were no longer significant. Other psychologic traits showed no association with angina. CONCLUSIONS: Sensitivity to physical symptoms, ischemic threshold and exercise tolerance are independently associated with angina, with sensitivity to physical symptoms having the stronger influence. The physiologic and psychologic mechanisms underlying symptom perception have an influence on angina that is independent of and additive to the severity of underlying ischemia.

Comparison between thallium-201, technetium-99m-sestamibi and technetium-99m-teboroxime planar myocardial perfusion imaging in detection of coronary artery disease.

Technetium-99m-sestamibi (MIBI) and 99mTc-teboroxime (TEBO) are two new myocardial perfusion imaging agents. The purpose of this prospective study was to compare MIBI and TEBO to 201TI planar imaging. Eighteen patients with significant coronary artery disease on coronary angiogram were submitted to three treadmill stress tests performed within 3 mo and were imaged with the three radiopharmaceuticals as follows. 1. TI: 2.2 mCi, immediate and delayed views (4 hr later, 8 min/view). 2. TEBO: 15-20 mCi at stress (1 min/view) and a second injection was repeated 4 hr later at rest (20-25 mCi). 3. MIBI: 15-18 mCi at stress (8 min/view) and 1-4 days later, 15-18 mCi at rest. Patients achieved similar levels of exercise. A blinded reading was performed by three observers. The left ventricle was divided into three segments/view and ischemic/normal wall ratios were also determined. Segmental comparison showed an agreement in 85% (138/162) of the segments between TI and TEBO, in 92% (149/162) between TI and MIBI and in 84% (136/162) between MIBI and TEBO. Abnormal TI, MIBI and TEBO studies were seen in 16 (89%), 16 (89%) and 15 (83%) patients, respectively, detecting 77, 75 and 65 abnormal segments. Ischemic-to-normal wall ratios were 0.75 +/- 0.06, 0.73 +/- 0.08 and 0.78 +/- 0.08 for TI, MIBI and TEBO, respectively. In conclusion, although the biologic characteristics of these agents are different, this study showed a good correlation between them in detection of significant coronary artery disease (high pretest likelihood population).

[Comparison between myocardial perfusion scintigraphy with thallium-201 and technetium-99m-Sestamibi (methoxy isobutyl isonitrile) for the detection of coronary atherosclerotic disease]. / Comparaison entre la scintigraphie de perfusion myocardique au Thallium-201 et au Technétium-99m-Sestamibi (methoxy isobutyl isonitrile) dans la détection de la maladie coronarienne athérosclérotique.

99mTc-SESTAMIBI is a new myocardial perfusion agent used in the detection of atherosclerotic coronary artery disease. In the present study, myocardial scintiscanning (on treadmill) with 99mTc-SESTAMIBI and 201-Thallium were compared, and both were compared with coronary angiography. Some 130 consecutive patients were evaluated within an interval of a few weeks with scintiscans of both 99mTc-SESTAMIBI and 201-Thallium: 82 of them were also examined by coronary angiography. Segmental analysis of the two series of scans revealed some correlation in 89.2% of the segments, while correlation of the final diagnosis showed agreement in 92% of cases. Compared to coronary angiography, sensitivity in the detection of CAD was found to be 75.8% for 201-Thallium and 72.5% for 99mTc-SESTAMIBI. The authors conclude that 99mTc-SESTAMIBI is a promising myocardial perfusion agent which displays an excellent correlation with 201-Thallium.

Clinical comparison between thallium-201 and Tc-99m-methoxy isobutyl isonitrile (hexamibi) myocardial perfusion imaging for detection of coronary artery disease.

99mTc-hexamibi (methoxy isobutyl isonitrile) is a new 99mTc-hexakis analog that can be used as a myocardial perfusion imaging agent. The purposes of this study were to compare 99mTc-hexamibi to 201Tl-thallous chloride myocardial stress scintigraphy in patients referred for investigation of chest pain and to evaluate the sensitivity of 99mTc-hexamibi in detection of coronary artery disease. One hundred patients were prospectively studied with both 201Tl and 99mTc-hexamibi planar imaging. Sixty five patients had a current coronary angiography. There was a total of 97 significantly (less than or equal to 70%) stenosed major coronary arteries. 99mTc-hexamibi (25 mCi) study was done within a week of the 201Tl scan with similar double products upon standard treadmil stress testing. Rest studies with 99mTc-hexamibi were obtained 24-48 h after the stress test using the same acquisition parameters and dose. Analysis was performed blind by three observers. The left ventricle was divided into five segments in each image. Analysis of 201Tl and 99mTc-hexamibi results in 1500 left ventricle segments showed an overall agreement in 1326/1500 (88.4%) segments. Correlation between the patient diagnosis on the 201Tl and 99mTc-hexamibi studies showed an agreement in 89 patients (89%). 201Tl revealed myocardial uptake defects in 526 segments, detecting 72 out of 97 (74.2%) significantly stenosed coronary arteries and 99mTc-hexamibi detected 513 segments corresponding to 68 (70.1%) stenosed arteries (no significant statistical difference). In conclusion, these results show a good correlation between 201Tl and 99mTc-hexamibi myocardial imaging in the detection of significant coronary artery disease.

Echocardiographic measurements and plasma levels of atrial natriuretic factor.

Atrial distension and pressure have been reported to be important for the release of atrial natriuretic factor (ANF) into the circulation. However, in mild essential hypertension, we have been unable to demonstrate an increase in plasma levels of ANF. To evaluate more precisely the lack of increase of ANF, we measured echocardiographically the diameters of the cardiac chambers and correlated these measurements with ANF values in normal subjects (n = 25), in patients with untreated essential hypertension (n = 20), and in patients with treated essential hypertension (n x 27). The plasma values of ANF were 21.9 +/- 2.8 pg/ml in the normal controls, 20.4 +/- 2.2 pg/ml in patients with untreated mild essential hypertension, and 32.6 +/- 2.8 pg/ml in patients with treated but uncontrolled essential hypertension (p less than 0.05). The plasma values of cGMP were 4.53 +/- 0.56 pmol/ml in the normal, 5.41 +/- 0.57 pmol/min in the patients with untreated essential hypertension, and 6.76 +/- 0.58 pmol/ml in treated essential hypertension (p less than 0.05). There were no significant differences in the size of the cardiac chambers between the three groups, except for the size of the right atrium, but there was a correlation between the ANF values and the size of the left atria (r = 0.29, p = 0.01, n = 72), as well as with the size of the intraventricular septum (IVS) in systole (r = 0.36, p = 0.002, n = 72). Since ANF levels are similar in mild untreated essential hypertension and normal volunteers, the ANF plasma levels could be a better reflection of the impact of the blood pressure on the myocardium than the level of blood pressure itself and indicate in patients the degree of cardiac impairment. On the other hand, there seems to be definitely an effect of treatment on the levels of ANF.

Same day injections of Tc-99m methoxy isobutyl isonitrile (hexamibi) for myocardial tomographic imaging: comparison between rest-stress and stress-rest injection sequences.

It has been shown that both rest and stress 99mTc-hexamibi myocardial perfusion imaging can be performed on the same day using two different doses injected within few hours (the first one at rest followed by a second at stress). In order to evaluate and compare 2 sequences (rest-stress and stress-rest) of 99mTc-hexamibi injections performed the same day, 18 patients with either abnormal 201Tl myocardial scan or abnormal coronary angiography were studied with 2 99mTc-hexamibi injections protocols. The rest-stress study was performed as follows: 7 mCi 99mTc-hexamibi was injected at rest. Single photon emission computed tomography (SPECT) was performed 60 min later. Immediately after the rest study, patients were injected at peak stress with 25 mCi 99mTc-hexamibi. Tomographic imaging was repeated 1 h later. Patients were submitted to the stress-rest protocol within 3 days. Tomographic imaging was done 1 h after a 7 mCi injection at stress. This study was followed by an injection of 25 mCi 99mTc-hexamibi at rest, a tomographic study was performed 60 min later. Myocardial sections were reconstructed in horizontal long, vertical long, and short axes. Data analysis also included polar map representation. A total of 324 segments were interpreted blind by 3 observers, there was an agreement in 283/324 (87.3%) segments between the 2 protocols. However, 24 segments (7.4%) judged ischemic on rest-stress were called scars on stress-rest.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial perfusion imaging with 99mTc-methoxy-isobutyl-isonitrile (MIBI): comparison of short and long time intervals between rest and stress injections. Preliminary results.

Unlike 201Tl, 99mTc-methoxy-isobutyl-isonitrile (99mTc-MIBI) does not redistribute in the myocardium after injection. Thus, two separate injections of this new myocardial perfusion agent are required to differentiate ischemia from scar. An injection at stress followed by a 2nd injection at rest performed 24 h later, or the inverse, has been proposed. This protocol is not ideal in clinical practice. It would be preferred if both injections were performed on the same day. Fifteen patients with significant coronary artery disease demonstrated by coronary angiography and with at least one ischemic segment on the myocardial 201Tl study were evaluated within two weeks with the following protocol. On the same day (short time interval protocol), 3 images, each of 10 min duration (anterior, 45 degrees LAO and 70 degrees LAO views) were performed between 30 to 60 min after the injection at rest of 7-10 mCi 99mTc-MIBI. On completion of the rest study, the patient received 25-30 mCi 99mTc-MIBI at stress and images were again obtained 30 to 60 min later. Two days later (long time interval protocol) a stress study alone was repeated using 10 mCi 99mTc-MIBI with the same imaging time. Qualitative and quantitative comparisons between the short and the long time interval studies were performed by four experienced observers. Both protocols showed the same number of ischemic segments (52/225) and fixed defects (19/225). The diagnostic information of images was judged similar in nine patients while the short protocol was judged superior to the long protocol in five patients and inferior in 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Thallium-201 myocardial imaging during pharmacologic coronary vasodilation: comparison of oral and intravenous administration of dipyridamole.

Although the diagnostic utility of thallium-201 myocardial imaging after dipyridamole infusion is well established, the intravenous form of the drug is not yet commercially available in North America. Fifty patients referred for coronary angiography were prospectively studied. Within a 2 week period, each patient underwent cardiac catheterization and thallium-201 myocardial imaging after both oral and intravenous dipyridamole administration. For the oral protocol, patients were randomly assigned to treatment with either 200 or 400 mg of dipyridamole in tablet form. Coronary artery stenoses of 70% or greater were considered significant. For the 25 patients who received a 200 mg oral dose of dipyridamole, the scintigraphic study showed perfusion defects in 65% of patients with significant coronary artery disease after the oral dose and in 85% of patients after the intravenous dose. For the 25 patients who received a 400 mg oral dose, the sensitivity of the scintigram was 84% after the oral dose and 79% after the intravenous dose. Except for headache and nausea, side effects were less severe and less frequent with oral (either 200 or 400 mg) than with intravenous dipyridamole. Because of the delayed and variable absorption of dipyridamole tablets, the oral studies required a longer period of medical supervision (45 to 60 minutes), and aminophylline was empirically administered after completion of the first set of thallium-201 images. It is concluded from this study that thallium-201 myocardial imaging after coronary vasodilation with a 400 mg oral dose of dipyridamole is a safe, widely available and reliable alternative for the evaluation of coronary artery disease in patients unable to achieve an adequate exercise level on stress testing.

Refractory variant angina controlled with combined drug therapy in a patient with a single coronary artery.

A young man with a single left coronary artery and refractory variant angina is described. Spontaneous coronary artery spasm developed during coronary arteriography at the site of a 50% fixed left anterior descending coronary artery stenosis. Frequent episodes of rest angina with transient ST segment elevation persisted in hospital in spite of treatment with three different calcium antagonist drugs. Symptoms disappeared only when the combination of nifedipine, diltiazem, isosorbide dinitrate, and nitroglycerin ointment were given. Ergonovine testing was used to objectively assess the response to treatment.

Chronic oral vasodilator therapy to control heart failure in postinfarction ventricular septal defect.

This report describes a 70-year-old woman with biventricular failure following an anteroseptal infarction complicated by interventricular septal rupture. Treatment with nitroprusside followed by oral hydralazine eliminated the failure and reduced the shunt from 2.75 to 1 to 1.7 to 1. She is asymptomatic post-discharge. Chronic medical therapy including oral vasodilators may be an acceptable alternative to surgery in a small minority of patients with this complication of myocardial infarction.