Clinical implications of cardiac (123)I-meta-iodobenzylguanidine scintigraphy and cardiac natriuretic peptides in patients with heart disease.

The purpose of this study was to evaluate whether or not cardiac sympathetic nerve activity, using (123)I-meta-iodobenzylguanidine ((123)I-MIBG) imaging, and cardiac natriuretic peptides (atrial and brain, ANP and BNP) were independent predictors of cardiac events, and, if so, which was the stronger predictor. Planar (123)I-MIBG images were obtained from 62 patients with heart disease. Plasma ANP and BNP levels, left ventricular ejection fraction (LVEF) by echocardiography, serum total cholesterol and triglyceride were measured. (123)I-MIBG was assessed as the heart-to-mediastinum (H/M) ratio of the delayed image and the washout rate (WoR) from the early to the delayed image. Patients were followed up for an average of 16.2 months, and 12 of 62 patients had cardiac events. Patients with events had significantly lower LVEF and H/M ratio compared with those without events. They had significantly higher WoR, ANP and BNP. By multivariate Cox proportional hazard analysis, (123)I-MIBG (H/M or WoR), ANP and BNP were independent predictors for cardiac events. Event-free survival using a Kaplan-Meier model, with a threshold value of 2.0 for H/M and 45% for WoR, showed that patients with H/M<2.0 and/or WoR>45% had a significantly poorer prognosis. These results suggest that (123)I-MIBG imaging and cardiac natriuretic peptides are useful tools for the evaluation of patients with heart disease, and that cardiac sympathetic nerve activity is a stronger predictor of cardiac events.

[Assessment of ischemic heart disease by dipyridamole stress electrocardiographic gated myocardial single photon emission computed tomography with technetium-99m tetrofosmin].

Simultaneous assessment of stress perfusion and rest function is possible with gated single photon emission computed tomography (SPECT) using stress injected technetium-99m (99mTc) tetrofosmin (TF). The feasibility of dipyridamole stress electrocardiographic gated myocardial SPECT (GSPECT) with TF was examined as an alternative to conventional stress/rest imaging. Fifty-one patients underwent stress GSPECT. 740 MBq of TF was administered 3 min after dipyridamole infusion. GSPECT acquisition was performed one hour after the injection. Additional rest SPECT was performed on another day only in patients with abnormal perfusion on stress images. Perfusion and thickening were analyzed visually on 17 segments of the left ventricle. Percentage of wall thickening (%WT) was also calculated in 17 segments of the polar map. Thirty-two of 51 patients (63%) had normal stress perfusion and normal rest thickening. Nineteen of 51 patients (37%) had abnormal perfusion on stress images. Among 157 abnormal perfusion segments of the 19 patients, 139 segments (89%) had thickening and the rest (11%) had no thickening. %WT was higher in the reversible segments with or without thickening. There was better agreement for the identification of normal segments and the presence of reversibility between stress GSPECT and the conventional stress/rest study in patients without previous myocardial infarction than in those with previous myocardial infarction (89% vs 79%). These results suggest that stress GSPECT may substitute for conventional stress/rest perfusion study in patients without previous myocardial infarction, allowing shorter examination time and lower cost. However, stress GSPECT does not replace the need for rest perfusion study in patients with previous myocardial infarction, because of underestimation of viability, but %WT may eliminate this underestimation.

Detection of mitochondrial DNA nucleotide 11778 point mutation of Leber hereditary optic neuropathy from archival stained histopathological preparations.

PURPOSE: We evaluated the availability of archival histopathological preparations for genetic diagnosis of Leber hereditary optic neuropathy (LHON). METHODS: Preparations of various tissues of an autopsied case of LHON, and of the optochiasmal arachnoidea of nine cases of bilateral optic neuropathy (BON) were studied to determine the presence of a point mutation of the mitochondrial DNA nucleotide (nt) 11778 using PCR method. RESULTS: An nt11778 point mutation was detected in all preparations of the autopsied case. Five preparations out of six BON cases who were diagnosed as LHON based on positive family history, revealed this point mutation. This mutation was also detected in two of three BON patients with no family history of the disease. CONCLUSION: The archival preparations were found to be available as materials of genetic diagnosis for LHON, which indicated that it would be capable to reevaluate retrospectively the pedigree of LHON and BON cases.

[Clinical usefulness of myocardial iodine-123-15-(p-iodophenyl)-3(R,S)-methyl-pentadecanoic acid distribution abnormality in patients with mitochondrial encephalomyopathy based on normal data file in bull's-eye polar map].

Visual interpretation of iodine-123-beta-15-(p-iodophenyl)-3(R,S)-methyl-pentadecanoic acid (123I-BMIPP) myocardial images cannot easily detect mild reduction in tracer uptake. Objective assessment of myocardial 123I-BMIPP maldistributions at rest was attempted using a bull's-eye map and its normal data file for detecting myocardial damage in patients with mitochondrial encephalomyopathy. Six patients, two with Kearns-Sayre syndrome and four with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), and 10 normal subjects were studied. Fractional myocardial uptake of 123I-BMIPP was also measured by dynamic static imaging to assess the global myocardial free fatty acid. These data were compared with the cardiothoracic ratio measured by chest radiography and left ventricular ejection fraction assessed by echocardiography. Abnormal cardiothoracic ratio and lower ejection fraction were detected in only one patient with Kearns-Sayre syndrome. Abnormal fractional myocardial uptake was detected in two patients (1.61%, 1.91%), whereas abnormal regional 123I-BMIPP uptake assessed by the bull's-eye map was detected in five patients (83%). All patients showed abnormal uptake in the anterior portion, and one showed progressive atrioventricular conduction abnormality and systolic dysfunction with extended 123I-BMIPP abnormal uptake. The results suggest that assessment based on the normal data file in a bull's-eye polar map is clinically useful for detection of myocardial damage in patients with mitochondrial encephalomyopathy.

[Anticancer drug-induced colitis--case report and review of the literature].

We encountered two chemotherapy cases related to anticancer drug-induced colitis. Case 1 was a 35-yo-female with a recurrence of ovarian cancer. She was treated with intraarterial infusion consisting of continuous 5-fluorouracil (250 mg/day 5 days/week x 4) following low-dose consecutive cisplatin (20 mg/day 5 days/ week x 1). The catheter was inserted into the abdominal aorta about 2 cm above the carina of the common iliac arteries. Six weeks after the start of chemotherapy, severe abdominal pain and melena occurred. Case 2 was a 68-yo-female with an endometrial cancer recurrence. The same intraarterial chemotherapy used in case 1 was was initiated. Four weeks after the start of chemotherapy, before intraarterial infusion of CDDP, she suffered from constipation and than diarrhea, abdominal pain and melena. Both cases were diagnosed as anticancer drug-induced colitis with the pathological findings from colon biopsy and the clinical course, and improved in about 1 month with the discontinuation of intraarterial infusion, fasting and TPN. Intraarterial infusion of only CDDP caused both patients no intestinal symptoms, so it is supposed that intraarterial infusion of 5-fluorouracil induced the colitis. Anticancer drug-induced colitis should be taken into consideration as a rare but possible course of chemotherapy-related complication with intraarterial infusion of 5-fluorouracil.

123I-MIBG myocardial imaging in hypertensive patients: abnormality progresses with left ventricular hypertrophy.

Twenty-seven patients with essential hypertension were prospectively studied with 123I-labeled metaiodobenzyl-guanidine (123I-MIBG) to assess the presence and location of impaired sympathetic innervation in hypertrophied myocardium. Thirteen patients had left ventricular hypertrophy on echocardiography, and 14 had normal echocardiograms. The wash out ratio of 123I-MIBG in these two groups did not differ significantly (35.3 +/- 6.1 and 35.4 +/- 5.1) but was higher than in control subjects (29.4 +/- 6.7). The delayed heart-to-mediastinum count ratio was lower in the patients with hypertrophy than in the patients without hypertrophy (1.93 +/- 0.28 and 2.22 +/- 0.21; p < 0.05) and the control subjects (1.93 +/- 0.28 and 2.33 +/- 0.25; p < 0.05). On SPECT imaging, abnormalities in segmental uptake were frequent at the posterior and postero-lateral wall in both groups, although the hypertrophic group had more significant impairment. Our results lead to the hypothesis that hypertension in more advanced stages may be associated not only with hypertrophic changes but also with more advanced regional impairment of cardiac sympathetic innervation.

Assessment of myocardial damage in dilated-phase hypertrophic cardiomyopathy by using indium-111-antimyosin Fab myocardial scintigraphy.

For the detection of myocardial cell damage, an 111In-antimyosin Fab study was carried out on seven patients (Group A) in the dilated phase of hypertrophic cardiomyopathy, seven patients (Group B) with dilated cardiomyopathy, and eight control patients (Group C). Imaging was done 48 hr after intravenous injection of 74 MBq of 111In-antimyosin Fab. Myocardial antimyosin uptake was visually graded as 0, +1, +2 or +3. A score of +2 or +3 was considered positive. The heart/lung ratio of antimyosin uptake (antimyosin index) also was determined. Antimyosin uptake was positive in seven (100%), nine (90%) and no (0%) patients in Groups A, B, and C, respectively. The antimyosin index in Groups A and B was 2.46 +/- 0.49 and 2.04 +/- 0.24, respectively, findings were significantly higher than that in Group C (1.51 +/- 0.13) (p less than 0.01). Positive biopsy findings were noted in only two patients in Group A. Thus, antimyosin uptake was increased in dilated phase hypertrophic cardiomyopathy and dilated cardiomyopathy, which suggests ongoing necrotic changes in these patients.

[Accumulation of 111In-antimyosin antibody at the focal site of inflammation].

An p6-year-old man with anterior acute myocardial infarction was administered antimyosin antibody labeled with 74 MBq (2 mCi) 111In, and abnormal hot activity was observed in the left lung by immunoscintigraphy. 67Ga-citrate scintigraphy also showed abnormal uptake in this lesion. At this time, this patient complained of fever and cough with sputum, and roentgenography showed a coin lesion-like shadow at the same location of the lung. By treatment with antibiotics, his symptom was improved and coin lesion-like shadow disappeared. So we thought the RI uptake area in the left lung was inflammatory lesion. This case suggests that 111In-antimyosin antibody can be trapped to the focal site of inflammation.

[Detection of restenosis after successful percutaneous transluminal coronary angioplasty (PTCA)--usefulness of exercise thallium scintigraphy].

We studied the efficacy of stress thallium scan in detecting restenosis after primary successful PTCA. There were 21 patients with angina pectoris and 16 patients with previous myocardial infarction. The sensitivity and the specificity of stress thallium scan in detecting restenosis were superior to those of stress electrocardiography or chest pain complained in follow-up period. In multi-vessel disease, we could assess the vessel developing restenosis more easily than stress electrocardiography. Initial thallium %UPTAKE RATIO was significantly improved after PTCA but redecreased in patients developing restenosis. In patients showing residual redistribution despite of not developing restenosis, we could judge vessel patency by gradually improving initial %UPTAKE RATIO after PTCA. Thus, stress thallium scan proved to be useful in detecting restenosis after PTCA.

[Serial assessment of denervated but viable myocardium following acute myocardial infarction by using 123I-MIBG and 201TlCl myocardial SPECT].

123I-MIBG is taken up by sympathetic nerve ending and provides a scintigraphic image of myocardial sympathetic innervation. We investigated the scintigraphic detection of denervated but viable myocardium following acute myocardial infarction by serial 123I-MIBG and 201TlCl myocardial SPECT. Fourteen patients were studied at acute (10 +/- 2 days) and chronic stage (86 +/- 10 days). Simultaneous dual SPECT was carried out after IV administration of 111 MBq (3 mCi) of 201TlCl and 123I-MIBG. The defect size of 123I-MIBG and 201TlCl were compared visually by using Bull's eye display generated from each myocardial SPECT. In all patients, 123I-MIBG defect showed larger compared to 201T1Cl defect at acute stage, which suggest the existence of denervated but viable myocardium. Of these patients, seven showed significant improvement of both defects, though 123I-MIBG defect showed slightly larger compared to 201TlCl defect, even at chronic stage. These patients had exercise induced thallium transient defect at infarcted area. The remaining 7 patients had no improvement of both defects at chronic stage, which suggest the complete scar at infarcted area. In addition to above study, 4 patients of old myocardial infarction demonstrated larger 123I-MIBG defect compared to 201TlCl defect even at old stage, which thought to be pathogenesis of ventricular tachycardia. In conclusion, 123I-MIBG could evaluate sympathetic denervation and reinnervation noninvasively in the patients with acute myocardial infarction.

[Assessment of myocardial damage in cardiomyopathy using 111In-antimyosin Fab myocardial scintigraphy].

111In-antimyosin Fab (AM) myocardial scintigraphy was carried out in (A) 10 patients with idiopathic dilated cardiomyopathy, (B) 7 with dilated phase of hypertrophic cardiomyopathy and (C) 8 with normal (control) individuals. Imaging was taken 48 hours after intravenous injection of 74 MBq of AM. Myocardial uptake of AM was evaluated qualitatively and quantitatively. Positive uptake was observed in 9/10 (90%), 7/7 (100%) and 0/8 (0%) in group A, B and C, respectively. AM index (heart/lung ratio) in group A and B were 2.04 +/- 0.24 and 2.46 +/- 0.49, values significantly higher than that obtained in the control patient without cardiomyopathy (1.51 +/- 0.13) (p less than 0.01). Positive monoclonal antimyosin antibody studies were highly prevalent in dilated cardiomyopathic and dilated phase of hypertrophic cardiomyopathic patients, even in the presence of negative right ventricular biopsy. It is suggested that this method was useful for the noninvasive assessment of active myocardial damage in these patients.

[Follow-up pulmonary perfusion scintigraphy pulmonary arterial embolization in two cases of familial pulmonary arteriovenous fistula].

Follow-up pulmonary perfusion scintigraphy in evaluating pulmonary arterial embolization were assessed by two cases of pulmonary familial arteriovenous fistula. Pulmonary arteriovenous fistula was found for brain abscess in the older brother, and for dyspnea on effort in the younger brother. Pulmonary arterial embolizations were performed. (older brother: 4 times, younger brother: 5 times) Before embolization, pulmonary perfusion scintigram showed pale defect, clear asymmetric perfusion between right and left lung, and clear renal visualization. On the other hand, after the embolization, clear multiple defects agreed with the sites of embolization, and asymmetric pulmonary perfusion and renal visualization disappeared. We conclude that follow-up pulmonary perfusion scintigraphy is useful to evaluate in pulmonary arteriovenous fistula after embolization.

Newly developed myocardial imaging by using single photon emission computed tomography (SPECT).

Thallium myocardial imaging is a useful technique to evaluate myocardial perfusion and myocardial viability in ischemic heart disease. However, myocardial imaging using single photon emission computed tomography (SPECT) and gamma-emitting radiopharmaceuticals has been recently developed for more precise evaluation of myocardial infarction and ischemia. The present study evaluates animal experiments and the clinical applications of these new myocardial imaging techniques. Areas considered on 1) myocardial necrosis assessed using 111In-antimyosin, 2) myocardial fatty acid metabolism assessed using 123I-beta-methyl-iodophenyl pentadecanoic acid (BMIPP) and 3) myocardial sympathetic neural activity assessed using 123I-metaiodobenzyl guanidine (MIBG). Dual energy SPECT using these new agents and thallium gives precise characterization of the myocardial tissue in the infarcted and ischemic area.

[Clinical variables that can cause the underestimation of the viable myocardium in the infarcted area: results of the sequential exercise thallium-201 myocardial scintigraphy].

Clinical variables that can cause the underestimation of the viable myocardium were examined in the sequential exercise thallium-201 study before and after PTCA. Among 60 patients who had documented myocardial infarction with single coronary artery disease, 43 patients had successful PTCA. Compared to the initial images after PTCA, the 4 hour-delayed images before PTCA had larger and more severe defect in the infarcted area of 14 patients (33%). This underestimated group had shorter period from the infarction to the stress study. (3.4 +/- 2.4 M vs. 7.1 +/- 9.2 M; p less than 0.05), and attained more maximal heart rate during the stress study. The numbers of the patients who had severe stenosis (greater than or equal to 99%) were more in the underestimated group (79% vs. 34%; p less than 0.01). The patients who have recent myocardial infarction, especially within three months, are likely to be underestimated their viable myocardium in the infarcted area, and this variable is dependent from their workload during the stress study and the severity of the stenotic lesion which also affect the estimation of the myocardial viability.

[Assessment of cerebral blood flow in intracerebral hematoma using IMP-SPECT].

To evaluate cerebral blood flow in intracerebral hemorrhage, we performed single photon emission computed tomography using N-isopropyl [I-123] p-iodoamphetamine (IMP-SPECT) in 20 patients. IMP-SPECT was carried out using rotating gamma camera at 30 min, and 4 hrs after injection. The results were compared with those by computed tomography (CT). In all cases, the extent of hematoma by IMP-SPECT was larger than that of CT. All cases were divided into 3 groups according to the extent of peripheral area zone of hematoma by IMP-SPECT. There were 10 cases with initial hypoperfusion and complete redistribution (Group I), 6 with initial perfusion defect and complete redistribution (Group II), 4 with initial perfusion defect and incomplete redistribution (Group III). Group III had extensive hematoma compared to Group I. The extent of peripheral area zone of hematoma could be considered as the decreased blood flow area by increased intracerebral pressure and the amplitude of redistribution may be correlated with celler damage. In conclusion, IMP-SPECT was useful to asses the viability of peripheral zone of hematoma.

[Scintigraphic assessment of patients with pulmonary thromboembolism by extent of perfusion defect and right ventricular function].

In 36 cases, severity of pulmonary thromboembolism (PTE) were determined with extent of perfusion defect (%PD) from pulmonary perfusion scintigraphy combined right ventricular ejection fraction (RVEF) from radionuclide angiocardiography. In 27 cases, follow-up scintigraphy was also done. After medical therapy, delta PD (= initial %PD-follow up %PD) was significant improved in patients with normal RVEF (greater than 38%) (19.40 +/- 15.58%: n = 15) than that in those with reduced RVEF (less than or equal to 38%) (0.00 +/- 3.9%). In follow-up studies, patients with larger %PD (greater than or equal to 40) showed poor prognosis than those with moderate or less %PD (less than 40). In conclusion, these both non-invasive indicators were proved to be useful for the evaluation not only the clinical severity but the prognosis of pulmonary thromboembolism.

[Assessment of myocardial necrosis by 111In-antimyosin F ab scintigraphy].

111In-antimyosin F ab (AM) myocardial scintigraphy was carried out in (A) 13 patients with acute myocardial infarction (9.9 +/- 2.2 days from the onset) and (B) 9 with myocarditis and/or dilated cardiomyopathy. Forty eight hours after injection of AM, the patients were injected with 74 MBq (2 mCi) of thallium-201 (TL). The two sets of Planar and SPECT image were obtained simultaneously using dual energy window sets. In group A, positive focal AM uptake was demonstrated in 12 (92%) patients. Higher AM uptake was observed in patients who had PTCR/PTCA. By combination with TL, it is useful to detect inferior infarction and to differentiate old from acute infarction. Dual SPECT images gave precise information about the infarcted area. In group B, positive diffuse AM uptake was demonstrated in 7 (77%) patients. In conclusion, AM myocardial scintigraphy was proven to be useful for the assessment of acute necrosis after myocardial infarction but also on-going necrosis of myocarditis and/or myopathy.

[Usefulness of coronary angioplasty (PTCA) of the infarct-related artery in patients with prior myocardial infarction--follow up of infarct zone pre- and post-angioplasty by stress thallium scan].

We studied the efficacy of coronary angioplasty (PTCA) of the infarct-related artery in 29 patients with prior myocardial infarction by stress thallium scan. Twenty-seven patients had anterior myocardial infarction (single LAD disease), one had inferior (single RCA disease) and one had posterior (single LCX disease). According to the stress-redistribution thallium scintigraphic finding before PTCA, the patients were classified in 4 groups; (A): three patients with complete redistribution. (B): fourteen patients with incomplete redistribution. (C): seven patients with partial redistribution. (D): five patients with no redistribution. After PTCA, the parameters of residual ischemia in the infarct area (% RD and Thallium ischemic score = TIS) were improved significantly but those of infarct size (RD% uptake and Defect Score = DS) were improved slightly in group A. In group B and C, % RD, TIS, RD% uptake and DS were all improved significantly. In group D, TIS was improved slightly and DS was improved slowly 3 months after PTCA. Group A had high probability of viable muscle and group D had high probability of scar at the infarct zone. Group B and C showed intermediate type between group A and D. The change of infarct area after PTCA was variable in 4 groups but both residual ischemia and infarct size decreased in all groups. Thus, PTCA of infarct-related coronary artery is useful even in the patients with prior myocardial infarction.