Scintigraphic studies on the etiology of Ampulla Cardiomyopathy

SummaryBackgroundAlthough there are many reports on Ampulla Cardiomyopathy, its etiologic mechanisms are not well known.AimEtiology of Ampulla Cardiomyopathy was investigated by myocardial scintigraphy with various nuclear tracers.Subjects and methodsIn nine patients with Ampulla Cardiomyopathy, myocardial scintigraphy was performed at acute, subacute and chronic phases. Total defect score (TDS) of tallium-201 (Tl) or technetrium-99m sestamibi (MIBI) myocardial perfusion and iodine-123-beta-methyl-p-iodophenyl penta-decanoic acid (BMIPP) scintigraphies was calculated. Cardio-mediastinal ratio (H/M) and washout rate (WR) of early and delayed images of iodine-123-meta-iodobenzylguanidine (MIBG) scintigraphy were also calculated. The patients in whom TDS of myocardial perfusion scintigraphy at acute phase was 0, were classified into group N (n=5) and those with TDS≥1 into group D (n=4).ResultsTDS of BMIPP at acute, subacute and chronic phases was higher in D than in N; 28.8±10.3 vs. 7.2±4.7 (p=0.0039), 15.5±2.1 vs. 1.0±0.8 (p<0.0001) and 2.7±1.2 vs. 0 (p=0.05), respectively. WR of MIBG at acute phase was also higher in D (50.3±5.7% vs. 36.6±10.5%, p=0.05). H/M (dH/M) on the delayed images and WR at chronic phase were not different between the two groups. H/M (eH/M) on the early images was lower in D. Blood noradrenaline (ng/ml) at acute phase was higher in D than in N (1.21±0.55 vs. 0.45±0.33, p<0.05). Left ventricular ejection fraction (LVEF) was decreased in both at acute phase but it was lower in D than in N (48.1±3.7% vs. 69.9±9.7%, p<0.05) at subacute phase.ConclusionThese findings suggest that the etiology of Ampulla Cardiomyopathy is neurologically stunned myocardium induced by coronary microcirculatory disorder.Due to the significant amount of time that was necessary for normalization of wall motion in the D group, myocardial scintigraphy is believed to be also useful in assessment of severity

A Pooled Analysis of Multicenter Cohort Studies of 123I-mIBG Imaging of Sympathetic Innervation for Assessment of Long-Term Prognosis in Heart Failure

ObjectivesThe study objectives were to create a cardiac metaiodobenzylguanidine (mIBG) database using multiple prospective cohort studies and to determine the quantitative iodine-123–labeled mIBG indices for identifying patients with chronic heart failure (HF) at greatest and lowest risk of lethal events.BackgroundAlthough the prognostic value of cardiac mIBG imaging in patients with HF has been shown, clinical use of this procedure has been limited. It is required to define universally accepted quantitative thresholds for high and low risk that could be used as an aid to therapeutic decision-making using a large cohort database.MethodsSix prospective HF cohort studies were updated, and the individual datasets were combined for the present patient-level analysis. The database consisted of 1,322 patients with HF followed up for a mean interval of 78 months. Heart-to-mediastinum ratio (HMR) and washout rate of cardiac mIBG activity were the primary cardiac innervation markers. The primary outcome analyzed was all-cause death.ResultsLethal events were observed in 326 patients, and the population mortality rate was 5.6%, 11.3%, and 19.7% at 1, 2, and 5 years, respectively. Multivariate Cox proportional hazard model analysis for all-cause mortality identified age (p < 0.0001), New York Heart Association (NYHA) functional class (p < 0.0001), late HMR of cardiac mIBG activity (p < 0.0001), and left ventricular ejection fraction (LVEF) (p = 0.0029) as significant independent predictors. Analysis of the 512-patient subpopulation with B-type natriuretic peptide (BNP) results showed BNP (p < 0.0001), greater NYHA functional class (p = 0.0002), and late HMR (p = 0.0011) as significant predictors, but LVEF was not. The receiver-operating characteristic–determined threshold of HMR (1.68) identified patients at significantly increased risk in any LVEF category. Survival rates decreased progressively with decreasing HMR, with 5-year all-cause mortality rates >7% annually for HMR <1.25, and <2% annually for HMR ≥1.95. Addition of HMR to clinical information resulted in a significant net reclassification improvement of 0.175 (p < 0.0001).ConclusionsPooled analyses of independent cohort studies confirmed the long-term prognostic value of cardiac mIBG uptake in patients with HF independently of other markers, such as NYHA functional class, BNP, and LVEF, and demonstrated that categoric assessments could be used to define meaningful thresholds for lethal event risk

Host Prostaglandin E2-EP3 Signaling Regulates Tumor-Associated Angiogenesis and Tumor Growth

Nonsteroidal antiinflammatories are known to suppress incidence and progression of malignancies including colorectal cancers. However, the precise mechanism of this action remains unknown. Using prostaglandin (PG) receptor knockout mice, we have evaluated a role of PGs in tumor-associated angiogenesis and tumor growth, and identified PG receptors involved. Sarcoma-180 cells implanted in wild-type (WT) mice formed a tumor with extensive angiogenesis, which was greatly suppressed by specific inhibitors for cyclooxygenase (COX)-2 but not for COX-1. Angiogenesis in sponge implantation model, which can mimic tumor-stromal angiogenesis, was markedly suppressed in mice lacking EP3 (EP3−/−) with reduced expression of vascular endothelial growth factor (VEGF) around the sponge implants. Further, implanted tumor growth (sarcoma-180, Lewis lung carcinoma) was markedly suppressed in EP3−/−, in which tumor-associated angiogenesis was also reduced. Immunohistochemical analysis revealed that major VEGF-expressing cells in the stroma were CD3/Mac-1 double-negative fibroblasts, and that VEGF-expression in the stroma was markedly reduced in EP3−/−, compared with WT. Application of an EP3 receptor antagonist inhibited tumor growth and angiogenesis in WT, but not in EP3−/−. These results demonstrate significance of host stromal PGE2-EP3 receptor signaling in tumor development and angiogenesis. An EP3 receptor antagonist may be a candidate of chemopreventive agents effective for malignant tumors

Creation and characterization of Japanese standards for myocardial perfusion SPECT: database from the Japanese Society of Nuclear Medicine Working Group

金沢大学大学院医学系研究科がん制御