Cardiac (123)I-labeled metaiodobenzylguanidine (MIBG) activity has significant incremental prognostic value, but the difference between the long-term prognostic value of MIBG imaging for ischemic cardiomyopathies and the long-term prognostic value of MIBG imaging for idiopathic cardiomyopathies is not clear. This study aimed to determine whether assessment of cardiac (123)I-MIBG activities in ischemic and idiopathic cardiomyopathies have equally prognostic values and whether the kinetics are different because of the underlying etiologies.After quantitative (123)I-MIBG imaging, 76 ischemic and 56 idiopathic cardiomyopathy patients were prospectively followed up for 54 mo. In addition to conventional parameters, cardiac (123)I-MIBG activity was quantified as a heart-to-mediastinum ratio (H/M) for early and late images and the washout kinetics were calculated using tomographic imaging. The data were compared with those obtained from 16 healthy volunteers.During follow-up, 29 deaths from heart failure, 11 sudden cardiac deaths, 2 deaths from arrhythmia, and 5 deaths from acute myocardial infarction were documented. Multivariate discriminant analysis using the Cox proportional hazards model showed that, in comparison with other variables, late H/M was the most powerful independent predictor of a lethal clinical outcome in ischemic (Wald chi(2) = 18.6502; P = 0.0000) and idiopathic (Wald chi(2) = 5.3394; P = 0.0208) groups. When patients with left ventricular ejection fraction (LVEF) < 40% were considered, late H/M had the greatest statistical power in both groups. Kaplan-Meier analysis showed late H/M to have an identical threshold (1.82) for both groups for identifying patients at risk of cardiac death. Likewise, when analysis was restricted to patients with an LVEF < 40%, the upper cutoff value of late H/M was 1.50 (P = 0.0358; log rank = 4.41) for ischemic patients and 2.02 (P = 0.0050; log rank = 7.86) for idiopathic patients. For patients with an LVEF < 40% and a late H/M less than the identified threshold of late H/M, the annual rate of cardiac death was greatest, 18.2%/y for the ischemic group and 11.9%/y for the idiopathic group.Cardiac (123)I-MIBG activity has the most powerful independent long-term prognostic value for both ischemic cardiomyopathy patients and idiopathic cardiomyopathy patients, indicating that both disease processes have common pathophysiologic and prognostic implications of impaired cardiac sympathetic innervation. Although combined testing of cardiac function and (123)I-MIBG activity is most likely to identify patients at increased risk of cardiac death, the underlying etiology of cardiac dysfunction may affect the threshold of (123)I-MIBG activity for the differentiation of high-risk patients.
Background There is considerable interest in the pleiotropic pharmacological action of sarpogrelate hydrochloride, a novel selective serotonin 2A receptor antagonist. In the present study the persistent insulin-sensitizing effects of sarpogrelate were investigated in non-diabetic and non-medicated diabetic patients with peripheral artery disease (PAD). Methods and Results Indices of insulin resistance (IR) (fasting immunoreactive insulin (IRI) and calculated homeostasis model assessment (HOMA-R)) and adiponectin were measured before and after 2 weeks of sarpogrelate administration (300 mg/day) in 24 patients (19 men, 76±9 years) with PAD. Sixteen of the 24 patients were examined after 3 months of treatment for assessment of the chronic effect of sarpogrelate on IR. After 2 weeks of treatment, significant decreases in fasting IRI (p=0.03) and HOMA-R (p=0.024), but not in adiponectin, were observed. After 3 months of treatment, significant decreases in fasting IRI (16.0±10.3 vs 9.2±2.0 μU/ml, p=0.03) and HOMA-R (4.30±2.83 vs 2.40±0.74, p=0.025) were maintained. Furthermore, adiponectin was significantly increased (8.11±4.13 vs 9.64±4.37 μg/ml, p=0.027). All of the examined HOMA-R had a significant correlation with all of the examined adiponectin (p<0.001, r=-0.441). Conclusions Sarpogrelate has a persistent insulin-sensitizing effect through adiponectin modification and might be beneficial for anti-atherosclerotic therapy, at least, in non-diabetic and non-medicated diabetic patients with PAD. (Circ J 2006; 70: 1451 - 1456)
Despite the diagnostic efficacy of stress myocardial perfusion imaging, the correlation between the actual perfusion tracer activity and diseased state of a coronary artery has not been studied in detail. We estimated exercise-related perfusion augmentation in relation to disease states of a coronary artery in diabetic and non-diabetic patients by a newly developed quantitative technetium (Tc)-99m-tetrofosmin myocardial imaging technique. Tc-99m-tetrofosmin tomographic imaging with an exercise-rest protocol was performed in 26 stable coronary patients and in 8 age-matched controls. Percent increase (%IR) in myocardial count during symptom-limited submaximal exercise-stress was calculated in 16 non-infarcted polar map segments and in each coronary territory by a subtraction technique with corrections for physical decay and injected tracer doses, and the results were compared with those of angiographically quantified coronary diameter stenosis (%DS). Percent IR and peak heart rate during exercise showed a positive linear correlation both in coronary territories with significant stenosis (%DS > or = 75%) and in control or nonstenotic (%DS < 75%) territories. The regression line in stenotic regions was, however. significantly (p < 0.01) shifted downward compared to that in non-stenotic regions. Percent IR in stenotic regions showed a significant inverse correlation with %DS. Coronary stenosis of 75% or more was identified by a %IR cutoff value of 40% with 77% sensitivity, 70% specificity, and an accuracy of 72%. In coronary territories with a %DS of less than 75%, %IR in diabetic patients was significantly lower (46+/-15%) than that in nondiabetic patients (61+/-25%). Thus, blunted exercise-related augmentation of myocardial uptake of Tc-99m-tetrofosmin correlates with the severity of coronary narrowing and diabetic state.
Despite its ability to quantify regional perfusion and function, there is no established method for quantification of regional perfusion and function by myocardial gated single photon emission computed tomography (SPECT). The aim of this study was to establish a quantitative index for regional perfusion and systolic function assessment using gated SPECT. Myocardial SPECT was performed at rest using 99mTc sestamibi with 8-frame gating in 62 consecutive patients. In addition to computation of left ventricular ejection fraction (LVEF), a new computerized method for quantifying, displaying and automatically grading regional data was developed. Regional function was quantified as wall motion, regional EF, and imaged based, count based, and normalized per cent wall thickenings (%WTs). Regional perfusion was assessed as a relative per cent peak count. Data were displayed on a 25-segmented polar map and automatically graded with a 5-point scale, and then summed scores were calculated. These quantitative parameters were compared to data from radionuclide ventriculography (RNV) and contrast left ventriculography. Gated SPECT had high reproducibilities for calculating global and regional ejection fractions and %WT indices (r = 0.811-0.984, P<0.0001), but measurement of wall motion was less reproducible (r = 0.555, SEE = 7.9, P<0.011). LVEF estimated by gated SPECT and summed perfusion scores correlated closely (P<0.0001) with angiographic LVEF. Among the summed function indices that correlated closely with LVEF, normalized %WT had the closest correlations with LVEF estimated by RNV (r = 0.657, P<0.0001) and by gated SPECT (r = 0.778, P<0.0001). Assessment by visual reviewing of cine-mode playback or by normalized %WT had greater overall sensitivity, specificity, and positive and negative predictive values for detecting impaired regional function among the functional parameters: 71%, 79%, 63% and 84% for cine format analysis, and 78%, 73%, 59% and 87% for normalized %WT, respectively. Thus, besides LVEF, quantitative gated SPECT can provide reproducible and reliable quantitative data on regional perfusion and function. Automated summed scores obtained by gated SPECT can reflect integrated abnormalities of regional perfusion and function of the left ventricle. Both visual analyses by cine-mode display and a functional map of normalized wall thickening have greater diagnostic values for detecting regional function deficit related to coronary artery disease.
