Masao Miyagawa

Effects of probucol and cilostazol alone and in combination on frequency of poststenting restenosis

The present study was conducted to assess the preventive effect of combined treatment with probucol, an antioxidant, and cilostazol, a phosphodiesterase inhibitor, against poststenting restenosis. Study patients were randomized to 4 modality groups 1 week before stenting: control, probucol (500 mg/day), cilostazol (200 mg/day), and probucol plus cilostazol. Treatment on these modalities was conducted from 5 prestent days until the poststenting follow-up evaluation (6 poststenting months). All patients received aspirin (81 mg/day). The efficacy of each modality against restenosis was evaluated in a total 126 patients with 165 coronary arterial lesions, using a quantitative method. The decrease in luminal diameter at the poststenting follow-up was 1.04 +/- 0.57 mm for controls, 0.88 +/- 0.82 mm for those taking probucol, 0.61 +/- 0.59 mm for those taking cilostazol (p <0.05 vs control), and 0.40 +/- 0.52 mm (p <0.01 vs control) for the combined treatment group. Restenosis rate per segment was 31.7% for controls, 16.7% for the probucol group, 12.5% for the cilostazol group (p <0.05 vs control), and 9.5% for the combined treatment group (p <0.05 vs the control). Neither mortality, myocardial infarction, stent thrombosis, or coronary bypass surgery, nor any serious complications were observed in the combined treatment group. Combined treatment with probucol and cilostazol has thus proved safe and effective in preventing acute poststenting complications and suppressing chronic restenosis.

Thallium-201 myocardial tomography with intravenous infusion of adenosine triphosphate in diagnosis of coronary artery disease

OBJECTIVES The purpose of this study was to evaluate the feasibility, safety and diagnostic accuracy of thallium-201 myocardial tomography with intravenous adenosine triphosphate (ATP) infusion in patients with suspected coronary artery disease. BACKGROUND Both ATP and adenosine are potent coronary vasodilators with a very short half-life. Several studies have confirmed that the diagnostic accuracy of adenosine thallium-201 scintigraphy is comparable to that with exercise. However, a high incidence of side effects, including atrioventricular (AV) block, has also been reported. Because the appropriate infusion rate for ATP has not yet been determined, this agent has not been tested in combination with myocardial scintigraphy. METHODS The study group included 253 consecutive patients who underwent thallium-201 myocardial tomography with ATP infusion (0.16 mg/kg body weight per min for 5 min). The occurrence of adverse effects was carefully monitored. Of the 120 patients with coronary angiography, 76 had significant coronary artery disease. Tomographic images were assessed visually and by computer-quantified polar maps, and they were compared with the results of coronary angiography. RESULTS Although 56% of the patients had some adverse effects, they were transient and mild. In all patients, the ATP infusion protocol could be completed, and no patient required aminophylline; AV block occurred in only 2% of the patients. The sensitivity and specificity were 88% and 80%, respectively, by visual analysis and 91% and 86%, respectively, by computer quantification. CONCLUSIONS Thallium tomography with ATP is feasible and has a diagnostic value similar to that with adenosine for detecting coronary artery disease. In addition, it may have fewer side effects than adenosine myocardial tomography.

Preventive effects of probucol on restenosis after percutaneous transluminal coronary angioplasty

This protocol was performed to elucidate the preventive effects of probucol on restenosis after percutaneous transluminal coronary angioplasty (PTCA). A total of 118 patients with 134 vessels undergoing successful PTCA was randomly and prospectively assigned to the probucol group (group P) or the control group (group C). The subjects consisted of 91 men and 27 women, with a mean age of 63.4 +/- 2.3 years. Sixty-six vessels of 59 patients in group P and 68 vessels of 59 patients in group C were evaluated by coronary angiography at 3 months after PTCA. Probucol (0.5 mg/day) was administered between >7 days before PTCA and 3 months after PTCA. The serum total cholesterol (TC) level and the formula low-density lipoprotein cholesterol (formula LDL-C) in group P decreased from 203.8 +/- 43.1 to 169.6 +/- 39.4 mg/dl and from 131.4 +/- 0.7 to 108.7 +/- 2.5 mg/dl, whereas in group C, the levels decreased only from 202.3 +/- 32.1 to 194.2 +/- 29.8 mg/dl and from 129.2 +/- 38.1 to 124.3 +/- 31.7 mg/dl, respectively. The restenosis rate was significantly lower in group P (19.7%; 13 of 66 vessels) than in group C (39.7%; 27 of 68 vessels; p < 0.05). In group P, the probucol blood concentration was significantly higher in the subjects without restenosis (31 +/- 9 microg/ml) than in those with restenosis (18 +/- 8 microg/ml; p < 0.01), but the serum TC and formula LDL-C levels were not significantly different between these two groups. In summary, long-term administration of probucol significantly reduces the incidence of restenosis after PTCA. it was suggested that the mechanism of this preventive effect was not reducing the serum TC or formula LDL-C levels, but rather an inhibitory action on smooth muscle cell proliferation.

Recommendations for (18)F-fluorodeoxyglucose positron emission tomography imaging for cardiac sarcoidosis: Japanese Society of Nuclear Cardiology recommendations.

Sarcoidosis is a systemic granulomatous disease that forms epithelioid cell granuloma (accompanied by infiltration of inflammatory cells) without caseous necrosis in organs throughout the body, including the lungs, lymph nodes, skin, eyes, heart, and muscles. Generally there is a good prognosis for spontaneous resolution of sarcoidosis; however, for cardiac-involvement sarcoidosis, the prognosis is extremely poor, and careful management is required. The most common cause of death from sarcoidosis is cardiac complications of the disease, and therefore early detection and treatment of these are very important in the management of cardiac-involvement sarcoidosis. Guidelines for the diagnosis of cardiac sarcoidosis were first published by Hiraga et al. [1] in 1992 (Table 1). These guidelines were modified by the joint committee of the Japan Society of Sarcoidosis and Other Granulomatous Disorders and the Japanese College of Cardiology in 2006 (Table 2) [2]. These modified guidelines stipulate the following: a histopathological or clinical diagnosis of sarcoidosis in organs other than the heart is essential, and the following cases should be diagnosed as cardiac sarcoidosis: (1) cases histopathologically diagnosed as positive for cardiac sarcoidosis on the basis of myocardial biopsy (histopathologically diagnosed group) and (2) cases with clinical findings indicating characteristic cardiac abnormalities including principal and secondary signs and symptoms (clinically diagnosed group) (Tables 1, 2). In the histopathologically diagnosed group, the positivity rate for detection of cardiac sarcoidosis may be low owing to sampling errors in myocardial biopsy. Hence, in actual clinical settings, the number of cases in the clinically diagnosed group is higher than in the histopathologically diagnosed group. Upon diagnosis of cardiac sarcoidosis, it is important to determine the disease activity to develop a treatment strategy, assess severity, predict prognosis, and Committee for diagnosis of cardiac sarcoidosis using 18F-FDG PET, Japanese Society of Nuclear Cardiology.

Relationship between insulin resistance and cardiac sympathetic nervous function in essential hypertension.

BACKGROUND It has been suggested that hyperinsulinemia and insulin resistance participate in the pathogenesis of hypertension, in part by activating sympathetic activity. OBJECTIVE We aimed to examine the relationship between insulin resistance and cardiac sympathetic nervous function in patients with essential hypertension using 123I-metaiodobenzylguanidine (MIBG) cardiac scintigraphy. METHODS AND RESULTS Twenty-eight patients (18 men) with essential hypertension and 11 (seven men) control individuals with a mean age of 55.8+/-3.3 years were recruited. Patients with diabetes mellitus, congestive heart failure or coronary artery disease were excluded from this study. To evaluate insulin resistance, we used steady-state plasma glucose (SSPG; mg/dl) levels measured by the SSPG method. To evaluate cardiac sympathetic nervous function, we calculated the heart-to-mediastinum ratio from the delayed MIBG image (H:M-D) and the mean washout rate (WOR, %). There were significant differences (P<0.01) in SSPG, H:M-D and WOR between the essential hypertension and control individual groups (125 versus 103 mg/dl, 2.2 versus 2.4, and 32 versus 23%, respectively). Stepwise regression analysis showed that SSPG and plasma norepinephrine level are independent predictors for the cardiac sympathetic nervous function obtained from MIBG scintigraphy. CONCLUSIONS These findings indicate that insulin resistance is significantly related to activation of the cardiac sympathetic nervous function associated with left ventricular hypertrophy in patients with essential hypertension.

Prognostic Value of Dipyridamole-Thallium Myocardial Scintigraphy in Patients With Kawasaki Disease

BACKGROUND Although coronary artery lesions are critical complications of Kawasaki disease, their long-term outcome is still unclear. It is sometimes difficult to monitor progressive changes from aneurysms to stenotic lesions because coronary angiography (CAG) cannot be repeated very often, especially in infants. Our prospective study was designed to evaluate the prognostic value of dipyridamole-thallium single-photon-emission CT (SPECT) in the long-term follow-up of patients with Kawasaki disease. METHODS AND RESULTS Of 459 consecutive patients with Kawasaki disease, coronary aneurysms were detected in 90 cases by echocardiography during the acute stage. After paired studies of selective CAG and SPECT were conducted, all patients were followed up and monitored for the occurrence of any cardiac events for > or =8 years. During the follow-up interval, there were 15 cardiac events (1 death, 5 infarctions, 2 coronary artery bypass graft operations, and 7 occurrences of unstable angina). Of patients who had some event, thallium redistribution was found on SPECT in 14 (93%, P<0.001). Of the various clinical and scintigraphic image variables, the presence of thallium redistribution was the best multivariate independent predictor of a late cardiac event (chi2=57.8, P<0.0001). The number of aneurysms detected on CAG added minimal statistical improvement to the model (chi2=1.9, P=0.0009). CONCLUSIONS Dipyridamole-thallium SPECT is safely performed and is useful and important for risk stratification in the long-term follow-up of patients with Kawasaki disease.

Incidence and characteristics of uterine leiomyomas with FDG uptake

ObjectiveUterine leiomyomas sometimes show focal 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) images that may result in a false-positive diagnosis for malignant lesions. This study was conducted to investigate the incidence and characteristics of uterine leiomyomas that showed FDG uptake.MethodsWe reviewed FDG-PET and pelvic magnetic resonance (MR) images of 477 pre-menopausal (pre-MP, age 42.1 ± 7.3 years) and 880 post-MP (age 59.9 ± 6.8 years) healthy women who underwent these tests as parts of cancer screening. Of 1357, 323 underwent annual cancer screening four times, 97 did three times, 191 did twice, and the rest were screened once. Focal FDG uptake (maximal standardized uptake value > 3.0) in the pelvis was localized and characterized on co-registered PET/MR images.ResultsUterine leiomyomas were found in 164 pre-MP and 338 post-MP women. FDG uptake was observed in 18 leiomyomas of 17 of the 164 (10.4%) pre-MP women and in 4 leiomyomas of 4 of the 338 (1.2%) post-MP women. The incidence was significantly higher in pre-MP women than in post-MP women (chi-square, P < 0.001). Of the 22, 13 showed signal intensity equal to or higher than that of the myometrium on T2-weighted MR images, which suggested abundant cellularity, whereas the majority of leiomyomas without FDG uptake showed low signal intensity. Of the 13 women, 12 examined more than twice showed substantial changes in the level of FDG uptake in leiomyomas each year with FDG uptake disappearing or newly appearing. These changes were observed frequently in relation with menopause or menstrual phases.ConclusionsLeiomyomas with focal FDG uptake were seen in both pre-and post-MP women with a higher incidence in pre-MP women. Abundant cellularity and hormonal dependency may explain a part of the mechanisms of FDG uptake in leiomyomas. It is important to know that the level of FDG uptake in leiomyomas can change and newly appearing FDG uptake does not necessarily mean malignant transformation.

Quantitative analysis of myocardial 18F-fluorodeoxyglucose uptake by PET/CT for detection of cardiac sarcoidosis

BACKGROUND Imaging with fluorodeoxyglucose (FDG) PET/CT is used to diagnose patients with cardiac sarcoidosis (CS). However, its specificity is relatively low. We aimed to demonstrate that higher diagnostic specificity for CS can be obtained using quantitative methodology to analyze PET/CT. METHODS A total of 125 consecutive patients with suspected CS were enrolled in the study. After clinical assessment and cardiac imaging studies, the patients underwent FDG PET/CT imaging after eating a low-carbohydrate diet followed by an overnight fast lasting ≥ 18 h. For visual analysis, fusion and maximum intensity projection images were reviewed. For quantitative analysis, the maximum standardized uptake value (SUV max) within the myocardium was obtained. RESULTS Of the 92 patients who met study inclusion criteria, 37 were diagnosed with CS. Myocardial SUV max was significantly higher in patients with CS compared with non-CS patients (9.5 ± 4.8 vs. 3.0 ± 1.7, p < 0.0001). The area under the curve by receiver operating characteristic analysis was 0.960 for SUV max. Using a cut-off value of 4.0, the sensitivity was 97.3% and specificity was 83.6% for diagnosing CS, which is more accurate than visual analysis. Moreover, SUV max was the only significant predictor of CS among 10 clinical and imaging variables. In 18 patients who received steroid therapy with a mean follow-up duration of 6.4 ± 5.2 months, SUV max significantly decreased from 9.8 ± 4.2 to 5.5 ± 3.5 (p = 0.003). CONCLUSION When evaluated by quantification of myocardial SUV max, FDG PET/CT imaging provides high sensitivity and specificity for diagnosing CS.

Qualitative and Quantitative Assessment of Adenosine Triphosphate Stress Whole-Heart Dynamic Myocardial Perfusion Imaging Using 256-Slice Computed Tomography

Background The aim of this study was to investigate the correlation of the qualitative transmural extent of hypoperfusion areas (HPA) using stress dynamic whole-heart computed tomography perfusion (CTP) imaging by 256-slice CT with CTP-derived myocardial blood flow (MBF) for the estimation of the severity of coronary artery stenosis. Methods and Results Eleven patients underwent adenosine triphosphate (0.16 mg/kg/min, 5 min) stress dynamic CTP by 256-slice CT (coverage: 8 cm, 0.27 s/rotation), and 9 of the 11 patients underwent coronary angiography (CAG). Stress dynamic CTP (whole–heart datasets over 30 consecutive heart beats in systole without spatial and temporal gaps) was acquired with prospective ECG gating (effective radiation dose: 10.4 mSv). The extent of HPAs was visually graded using a 3-point score (normal, subendocardial, transmural). MBF (ml/100g/min) was measured by deconvolution. Differences in MBF (mean ± standard error) according to HPA and CAG results were evaluated. In 27 regions (3 major coronary territories in 9 patients), 11 coronary stenoses (> 50% reduction in diameter) were observed. In 353 myocardial segments, HPA was significantly related to MBF (P < 0.05; normal 295 ± 94; subendocardial 186 ± 67; and transmural 80 ± 53). Coronary territory analysis revealed a significant relationship between coronary stenosis severity and MBF (P < 0.05; non-significant stenosis [< 50%], 284 ± 97; moderate stenosis [50–70%], 184 ± 74; and severe stenosis [> 70%], 119 ± 69). Conclusion The qualitative transmural extent of HPA using stress whole-heart dynamic CTP imaging by 256-slice CT exhibits a good correlation with quantitative CTP-derived MBF and may aid in assessing the hemodynamic significance of coronary artery disease.

Ischemic “memory image” in acute myocardial infarctio of123I-BMIPP after reperfusion therapy: A comparison with99mTc-pyrophosphate and201Tl dual-isotope SPECT

Ischemic “memory image” is a phenomenon of123I-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) in which an area at risk of acute myocardial infarction (AMI), could be detected as a defect in a couple of weeks even after successful reperfusion therapy.The purpose of this study was to clarify the incidence of the ischemic “memory image” of123I-BMIPP in patients with AMI by comparing99mTc-PYP and201Tl dual-isotope SPECT.Materials consisted of 14 patients with successfully reperfused AMI and 20 patients with old myocardial infarction (OMI). All AMI patients underwent PYP/Tl dual-isotope SPECT within 1 week after the onset of AMI, and BMIPP SPECT was performed within 1 week after the PYP/Tl dual-isotope SPECT. The extent and severity of the defect of BMIPP and Tl were visually scored into four grades: 0=no defect to 3=large or severe defect. These scores were compared.PYP positive AMI lesions were concordant with BMIPP defects (13/14). In AMI, both the extent and severity scores of BMIPP were higher than201Tl (p<0.001). Differences (BMIPP-Tl) of extent and severity scores were greater in AMI than in OMI (p<0.001).In conclusion, the ischemic “memory image” obtained by means of the BMIPP is a common phenomenon (13/14) in AMI, and helpful in evaluating the area at risk.