Long-term prognostic value of low-dose normal stress-only myocardial perfusion imaging by wide beam reconstruction: A competing risk analysis.

BACKGROUND: A normal stress myocardial perfusion single-photon emission computed tomography (MPS) is associated with a good clinical outcome. New iterative algorithms, such as wide beam reconstruction (WBR), which improve image interpretation with half-dose or half-time acquisition, have been proposed for cardiac MPS. The aim of this study was to assess the long-term predictive value of a low-dose normal stress-only MPS with WBR using conventional Anger camera in patients with known or suspected coronary artery disease (CAD). METHODS AND RESULTS: A total of 2106 patients with known or suspected CAD and normal perfusion at half-dose stress-only MPS protocol were followed for a mean of 6.6 ± 2.7 years. MPS data were reconstructed with WBR iterative algorithm. End-point events were cardiac death or nonfatal myocardial infarction. Noncardiac death was considered the competing event. During follow-up, 149 cardiac events occurred with an annualized event rate of 1.2%. Independent predictors of cardiac events at Cox analysis were age, male gender, diabetes mellitus, previous myocardial infarction and the need for pharmacologic stress testing. At Fine-Gray analysis the cumulative incidence of cardiac events progressively increases with age and in the presence of diabetes for any combination of gender and stress type. Survival tree analysis confirmed that long-term prognosis considerably varies according of risk factors profile. CONCLUSIONS: Low-dose normal stress-only WBR MPS has a reliable long-term prognostic value in patients with suspected or known CAD. This finding supports the introduction of such a method into clinical practice with a consistent dose optimization in the interest of patients and exposed staff.

Temporal trends of abnormal myocardial perfusion imaging in a cohort of Italian subjects: Relation with cardiovascular risk factors.

BACKGROUND: The frequency of abnormal stress single-photon emission computed tomography myocardial perfusion imaging (MPS) has decreased over the past decades despite an increase in the prevalence of cardiovascular risk factors. This study evaluated the temporal trend of abnormal stress MPS and its relationship with risk factors in a cohort of Italian subjects. METHODS: We included all patients who underwent clinically indicated stress MPS at our academic center between January 2006 and December 2017. Patients were assessed for change in demographics, clinical symptoms, risk factors, and frequency of abnormal and ischemic MPS. RESULTS: A total of 8,886 stress MPS studies were performed (3,350 abnormal). Age, male gender, diabetes, smoking, and angina were independent predictors of abnormal MPS. There was a slight decline in the frequency of abnormal (from 39 to 36%, P < 0.05) and ischemic (from 25 to 22%, P < 0.01) MPS during the study period, while the percentage of patients with hypertension, hypercholesterolemia, smoking, and angina increased. The Cochran-Mantel-Haenszel test indicates that the likelihood of having an abnormal MPS did not change over time for age, diabetes, smoking, and a history of coronary artery disease (CAD), increased for hypertension and hypercholesterolemia and decreased for male compared to female gender. CONCLUSIONS: In our cohort of Italian subjects, there was a slight temporal decline in the frequency of abnormal and ischemic MPS despite an increase over time in the prevalence of many cardiac risk factors. These results strengthen the need to develop more effective strategies for appropriately referring patients to cardiac imaging procedures.

Long-term prognostic value of coronary artery calcium scanning, coronary computed tomographic angiography and stress myocardial perfusion imaging in patients with suspected coronary artery disease.

BACKGROUND: We compared the long-term prognostic value of coronary artery calcium (CAC) scanning, coronary computed tomographic angiography (CCTA), and stress single-photon emission computed tomography myocardial perfusion imaging (MPI) in patients with suspected coronary artery disease (CAD). METHODS AND RESULTS: A total of 164 patients were studied. CAC score was measured according to the Agatston method and patients were categorized into 3 groups (0, 1-300, and >300). The following events were recorded: cardiac death, nonfatal infarction, and unstable angina requiring revascularization. Follow-up was 95% complete during a mean period of 82 ± 34 months. During follow-up, 22 events occurred (14% cumulative event rate). Event-free survival decreased with worsening of CAC score category (P < .001) and it was worse (P < .001) in patients with significant CAD (≥50% stenosis) and in those with stress-induced ischemia (summed difference score >2). At multivariable analysis, CAC (P = .001) and ischemia (P = .012) were independent predictors of events. MPI data added prognostic information to a model including clinical variables, CAC and CCTA findings, increasing the global Chi-square from 36.2 to 41.9 (P = .013). The decision curve analyses in patients with CAC score >0 indicate that the prognostic model including MPI resulted in a higher net benefit across a wide range of decision threshold probabilities. CONCLUSIONS: CAC and MPI, but not CCTA, are independent predictors of cardiac events. Stress MPI appears to improve risk stratification over clinical variables, CAC scanning and CCTA findings.

Long-Term Survival Benefit of Coronary Revascularization in Patients Undergoing Stress Myocardial Perfusion Imaging.

BACKGROUND: We assessed the relationship between clinical outcome and coronary revascularization according to stress-gated myocardial perfusion single-photon emission computed tomography (MPS) in an observational series of patients with suspected or known coronary artery disease (CAD), on long-term follow-up. METHODS AND RESULTS: The study group consisted of 2,059 patients. During a median follow-up of 61 months, 184 events occurred (126 cardiac deaths and 58 non-fatal MI). The impact of revascularization during follow-up on event-free survival was evaluated using an extended Cox regression model, adjusting for potential clinical and MPS confounders. Revascularization was treated as a binary non-reversible time-dependent covariate. Predefined interactions tested were: (1) revascularization and summed difference score (SDS); (2) revascularization and post-stress left ventricular (LV) ejection fraction (EF); and (3) SDS and post-stress LVEF. Revascularization had a significant effect on event-free survival (adjusted HR, 0.19; P<0.001). Significant interactions were found between revascularization and SDS (P=0.045), and between LVEF and SDS (P=0.015). The protective effect of revascularization increased as SDS increased. For SDS <6 the reduction in HR was detectable only for reduced LVEF. CONCLUSIONS: Both the degree of stress-induced ischemia and LVEF predict the effect of revascularization on outcome in patients with suspected or known CAD. The protective effect of revascularization appears to be greater in patients with severe ischemia and preserved LVEF.

Added prognostic value of ischaemic threshold in radionuclide myocardial perfusion imaging: a common-sense integration of exercise tolerance and ischaemia severity.

PURPOSE: Reversible ischaemia at radionuclide myocardial perfusion imaging (MPI) accurately predicts risk of cardiac death and nonfatal myocardial infarction (major adverse cardiac events, MACE). This prognostic penetrance might be empowered by accounting for exercise tolerance as an indirect index of ischaemia severity. The present study aimed to verify this hypothesis integrating imaging assessment of ischaemia severity with exercise maximal rate pressure product (RPP) in a large cohort of patients with suspected or known coronary artery disease (CAD). METHODS AND RESULTS: We analysed 1,502 consecutive patients (1,014 men aged 59 ± 10 years) submitted to exercise stress/rest MPI. To account for exercise tolerance, the summed difference score (SDS) was divided by RPP at tracer injection providing a clinical prognostic index (CPI). Reversible ischaemia was documented in 357 patients (24 %) and was classified by SDS as mild (SDS 2-4) in 180, moderate (SDS 5-7) in 118 and severe (SDS >7) in 59. CPI values of ischaemic patients were clustered into tertiles with lowest and highest values indicating low and high risk, respectively. CPI modified SDS risk prediction in 119/357 (33 %) patients. During a 60-month follow-up, MACE occurred in 68 patients. Kaplan-Meier analysis revealed that CPI significantly improved predictive power for MACE incidence with respect to SDS alone. Multivariate Cox analysis confirmed the additive independent value of CPI-derived information. CONCLUSION: Integration of ischaemic threshold and ischaemia extension and severity can improve accuracy of exercise MPI in predicting long-term outcome in a large cohort of patients with suspected or known CAD.

Warranty period of normal stress myocardial perfusion imaging in diabetic patients: a propensity score analysis.

BACKGROUND: We evaluated the relationship between diabetes and temporal characteristics of cardiac risk at long-term follow-up in a propensity score-matched cohort of diabetic and non-diabetic patients with normal stress myocardial perfusion single-photon emission computed tomography (MPS). METHODS AND RESULTS: We studied 828 consecutive patients with suspected or known coronary artery disease and normal perfusion at stress MPS. To account for differences in baseline characteristics between diabetics and non-diabetics, we created a propensity score-matched cohort considering clinical variables and stress type. After matching, clinical characteristics were comparable in 260 diabetic and 260 non-diabetic patients. All patients were followed for at least 1 year (median 53 months). End-point events were cardiac death or nonfatal myocardial infarction. At Cox analysis, diabetes (hazard ratio 3.9, P < .01) and post-stress left ventricular ejection fraction (LVEF) ≤45% (hazard ratio 4.1, P < .01) were independent predictors of events. At parametric analysis, non-diabetic patients with post-stress LVEF >45% remained at low risk for the entire length of follow-up, while the highest probability of events and the major risk acceleration was observed in patients with diabetes and post-stress LVEF ≤45%. CONCLUSIONS: After a normal stress MPS, diabetic patients are at higher risk for cardiac events than non-diabetic subjects also after balancing clinical characteristics and stress type by propensity score analysis. The warranty period of a normal stress MPS varies according to diabetic status and post-stress LVEF.

Prognostic value of normal stress myocardial perfusion imaging in diabetic patients: a meta-analysis.

BACKGROUND: The prognostic value of normal stress myocardial perfusion single-photon emission computed tomography (MPS) in patients with diabetes has only been evaluated in single-center studies of relatively limited sample size. We performed a meta-analysis of published studies, including diabetic patients with known or suspected coronary artery disease (CAD), to assess the predictive value for adverse cardiac ischemic events of normal stress MPS. METHODS AND RESULTS: Studies published between January 1990 and December 2013 were identified by database search. We included studies using stress MPS to evaluate diabetic patients with known or suspected CAD and providing data on clinical outcomes of non-fatal myocardial infarction or cardiac death with a follow-up time ≥12 months. A total of 14 studies were finally included, recruiting 13,493 patients. The negative predictive value (NPV) for non-fatal myocardial infarction and cardiac death of normal MPS was 94.92% (95% confidence interval 93.67-96.05), during a weighted mean follow-up of 36.24 months, resulting in estimated event rate after a negative test equal to 5.08% (95% confidence interval 3.95-6.33). The corresponding annualized event rate after a negative test was 1.60% (95% confidence interval 1.21-2.04). CONCLUSIONS: Stress MPS has a high NPV for adverse cardiac events in diabetic patients with known or suspected CAD leading to define a "relatively low-risk" patients category.

Myocardial perfusion imaging after coronary revascularization: a clinical appraisal.

Revascularization procedures, including percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG), are performed in many patients with coronary artery disease. Despite the effectiveness of these procedures, different follow-up strategies need to be considered for the management of patients after revascularization. Stress myocardial perfusion single-photon emission computed tomography (MPS) is a suitable imaging method for the evaluation of patients who have undergone PCI or CABG, and it has been used in the follow-up of such patients. Radionuclide imaging is included in the follow-up strategies after PCI and CABG in patients with symptoms, but guidelines warn against routine testing of all asymptomatic patients after revascularization. After PCI, in the absence of symptoms, radionuclide imaging is recommended and indicated as appropriate after incomplete or suboptimal revascularization and in specific asymptomatic patient subsets. On the other hand, the value of MPS late after CABG in risk stratification has been demonstrated even in the absence of symptoms. Thus, given the adverse outcome associated with silent ischaemia, it can be speculated that all patients regardless of clinical status should undergo stress testing late after revascularization. Larger prospective studies are needed to assess whether stress MPS will have an impact on the outcome in asymptomatic patients after revascularization.

Transient ischemic dilation in SPECT myocardial perfusion imaging for prediction of severe coronary artery disease in diabetic patients.

BACKGROUND: Transient ischemic dilation (TID) of the left ventricle during stress myocardial perfusion SPECT (MPS) has been shown to be a useful marker of severe coronary artery disease (CAD). However, investigations in diabetic patients with available coronary angiographic data are still limited. We evaluated the incremental diagnostic value of TID in identifying the presence of angiographically severe CAD in diabetic patients. METHODS AND RESULTS: TID ratio values were automatically derived from rest-stress MPS in 242 diabetic patients with available coronary angiography data. A cutoff of ≥1.19 was considered to represent TID. Severe CAD (≥70% stenosis in the proximal left anterior descending artery or the left main artery, or ≥90% stenosis in two or three vessels) was identified in 69 (29%) patients. At multivariate analysis, the best independent predictors of severe CAD were summed stress score and TID (both P < .001). At incremental analysis, the addition of TID improved the power of a model including clinical data and summed stress score, increasing the global χ(2) value from 14.3 to 28.2 (P < .01). The best cutoff of summed stress score for identifying patients with severe CAD was ≥8. When the TID ratio was considered in patients with summed stress score between 3 and 7, the sensitivity for diagnosing severe CAD significantly improved from 71% to 77% (P < .05). In the overall study population, the net reclassification improvement by adding TID to a model including clinical data and summed stress score in the prediction of severe CAD was 0.40 (P < .005). CONCLUSIONS: TID ratios obtained from rest-stress MPS provide incremental diagnostic information to standard perfusion analysis for the identification of severe and extensive CAD in diabetic patients.

Post-stress left ventricular ejection fraction drop in patients with diabetes: a gated myocardial perfusion imaging study.

BACKGROUND: To evaluate the relevance of stress-induced decrease in left ventricular ejection fraction (LVEF) in patients with type-2 diabetes. METHODS: A total of 684 diabetic patients with available rest and post-stress gated myocardial perfusion single-photon emission computed tomography (MPS) data were enrolled. An automated algorithm was used to determine the perfusion scores using a 17-segment model. LVEF drop was considered significant if the post-stress LVEF was ≥5% below the rest value. Follow-up data were available in 587 patients that were followed for the occurrence of cardiac death, nonfatal myocardial infarction, or unstable angina requiring revascularization. RESULTS: A post-stress LVEF drop ≥5% was observed in 167 (24%) patients. Patients with LVEF drop had higher summed stress score (p < 0.05), summed difference score (p < 0.001), and rest LVEF (p < 0.001) compared to patients without. Conversely, summed rest score, a measure of infarct size, was comparable between the two groups. At multivariable analysis, summed difference score and rest LVEF were independent predictors (both p < 0.001) of post-stress LVEF drop. Myocardial perfusion was abnormal in 106 (63%) patients with post-stress LVEF drop and in 296 (57%) of those without (p = 0.16). The overall event-free survival was lower in patients with post-stress LVEF drop than in those without (log rank χ2 7.7, p < 0.005). After adjusting for clinical data and MPS variables, the hazard ratio for cardiac events for post-stress LVEF drop was 1.52 (p < 0.01). CONCLUSIONS: In diabetic patients stress-induced ischemia is an independent predictor of post-stress LVEF drop; however, a reduction in LVEF is detectable also in patients with normal perfusion. Finally, post-stress LVEF drop increases the risk of subsequent cardiac events in diabetic patients.

Myocardial perfusion imaging and risk classification for coronary heart disease in diabetic patients. The IDIS study: a prospective, multicentre trial.

PURPOSE: To determine whether stress-rest myocardial perfusion single-photon emission (MPS) computed tomography improves coronary heart disease (CHD) risk classification in diabetic patients. METHODS: In 822 consecutive diabetic patients, risk estimates for a CHD event were categorized as 0% to <3%, 3% to <5%, and ≥5% per year using Cox proportional hazards models. Model 1 used traditional CHD risk factors and electrocardiography (ECG) stress test data and model 2 used these variables plus MPS imaging data. We calculated the net reclassification improvement (NRI) and compared the distribution of risk using model 2 vs. model 1. CHD death, myocardial infarction and unstable angina requiring coronary revascularization were the outcome measures. RESULTS: During follow-up (58 ± 11 months), 148 events occurred. Model 2 improved risk prediction compared to model 1 (NRI 0.25, 95% confidence interval, CI, 0.15-0.34; p < 0.001). Overall, 301 patients were reclassified to a higher risk category, with an event rate of 28%, and 26 to a lower risk category, with an event rate of 15%. Among patients at 3% to <5% risk, 53% were reclassified at higher risk and 25% at lower risk (NRI 0.42, 95% CI 0.07-0.76; p < 0.05). The cost per NRI was $880.80 for MPS imaging as compared to an outpatient visit with an ECG stress test. CONCLUSION: The addition of MPS imaging data to a prediction model based on traditional risk factors and ECG stress test data significantly improved CHD risk classification in patients with diabetes.

Addition of atropine to submaximal exercise stress testing in patients evaluated for suspected ischaemia with SPECT imaging: a randomized, placebo-controlled trial.

PURPOSE: To evaluate the effects of the addition of atropine to exercise testing in patients who failed to achieve their target heart rate (HR) during stress myocardial perfusion imaging with single-photon emission computed tomography (SPECT). METHODS: The study was a prospective, randomized, placebo-controlled design. Patients with suspected or known coronary artery disease who failed to achieve a target HR (≥85% of maximal predicted HR) during exercise SPECT imaging were randomized to receive intravenous atropine (n=100) or placebo (n=101). RESULTS: The two groups of patients did not differ with respect to demographic or clinical characteristics. A higher proportion of patients in the atropine group achieved the target HR compared to the placebo group (60% versus 3%, p<0.0001). SPECT imaging was abnormal in a higher proportion of patients in the atropine group as compared to the placebo group (57% versus 42%, p<0.05). Stress-induced myocardial ischaemia was present in more patients in the atropine group as compared to placebo (47% versus 29%, p<0.01). In both groups of patients, no major side effects occurred. CONCLUSION: The addition of atropine at the end of exercise testing is more effective than placebo in raising HR to adequate levels, without additional risks of complications. The use of atropine in patients who initially failed to achieve their maximal predicted HR is associated with a higher probability of achieving a diagnostic myocardial perfusion study.

Incremental prognostic value of coronary flow reserve assessed with single-photon emission computed tomography.

BACKGROUND: We assessed the prognostic value of coronary flow reserve (CFR) estimated by single-photon emission computed tomography (SPECT) in patients with suspected myocardial ischemia. METHODS AND RESULTS: Myocardial perfusion and CFR were assessed in 106 patients using dipyridamole/rest Tc-99m sestamibi SPECT and follow-up was obtained in 103 (97%) patients. Four early revascularized patients were excluded and 99 were assigned to normal (summed stress score <3) vs abnormal myocardial perfusion and to normal (≥2.0) vs abnormal CFR. During the follow-up (5.8 ± 2.1 years), 28 patients experienced a cardiac event (cardiac death, nonfatal myocardial infarction, and late revascularization). Abnormal perfusion (P < .01) and abnormal CFR (P < .05) were independent predictors of cardiac events at Cox proportional hazard regression analysis. Also in patients with normal perfusion, abnormal CFR was associated with a higher annual event rate compared with normal CFR (5.2% vs 0.7%; P < .05). CFR data improved the prognostic power of the model including clinical and myocardial perfusion data increasing the global chi-square from 18.6 to 22.8 (P < .05). Finally, at parametric survival analysis, in patients with normal perfusion the time to achieve ≥2% risk of events was >60 months in those with normal and <12 months in those with abnormal CFR. CONCLUSIONS: Myocardial perfusion findings and CFR at SPECT imaging are both independent predictors of cardiac events. Estimated CFR provides incremental prognostic information over those obtained from clinical and myocardial perfusion data, particularly in patients with normal perfusion findings.

A rare case of congenital aneurysm of the portal system at level of spleno-porto-mesenteric confluence complicated by massive thrombosis.

Portal venous aneurysm is a rare and potential dangerous vascular pathology, which can result in thrombosis or rupture. It may be congenital or acquired. Acquired form can be related mainly to portal hypertension, chronic hepatic disease, and trauma. We present a peculiar case of a congenital aneurysm involving the hepatic portal system in nearly all its extra-hepatic components: the main portal trunk, the spleno-porto-mesenteric confluence and the distal segment of splenic, superior, and inferior mesenteric veins, in a 20-year-old male patient. The aneurysm was complicated by massive thrombosis in absence of further predisposing factors.

Incremental prognostic value of cardiac single-photon emission computed tomography after nitrate administration in patients with ischemic left ventricular dysfunction.

BACKGROUND: We evaluated the incremental prognostic value of viability assessment by nitrate single-photon emission computed tomography (SPECT) in patients with ischemic left ventricular (LV) dysfunction. METHODS AND RESULTS: One hundred and sixty-four patients with previous myocardial infarction and LV dysfunction (ejection fraction 29% +/- 15%) underwent two Tc-99m sestamibi SPECT studies, under control conditions and after sublingual nitrate administration, for evaluation of myocardial viability. In each patient, viability was defined as the presence of > or = 2 severely dysfunctional segments with preserved tracer uptake (> or = 55% of peak activity). Cardiac death, myocardial infarction, and late (> 2 months) revascularization were considered events. Follow-up was 98% complete at a mean period of 30 +/- 24 months. At baseline SPECT, 119 (73%) patients had evidence of viable myocardium, while 45 (27%) did not. Of these latter patients, 18 (40%) had evidence of viability after nitrate administration. Cardiac events occurred in 58 (35%) patients. Cumulative probability of event-free survival was similar in patients with and without viability at baseline SPECT (log rank 0.3, P = NS), while it was lower in patients with viability at nitrate SPECT compared to those without (log rank 6.3, P < .01). The addition of nitrate SPECT data significantly improved the prognostic power of the model including clinical, functional, angiographic, and baseline SPECT data (P < .01). CONCLUSIONS: In patients with previous myocardial infarction and LV dysfunction, nitrate SPECT imaging provides incremental prognostic information over those obtained from clinical, functional, angiographic variables, and baseline SPECT data.

A New Relational Database Including Clinical Data and Myocardial Perfusion Imaging Findings in Coronary Artery Disease.

BACKGROUND: The aim of this study was to test a relational database including clinical data and imaging findings in a large cohort of subjects with suspected or known Coronary Artery Disease (CAD) undergoing stress single-photon emission computed tomography (SPECT) myocardial perfusion imaging. METHODS: We developed a relational database including clinical and imaging data of 7995 subjects with suspected or known CAD. The software system was implemented by PostgreSQL 9.2, an open source object-relational database, and managed from remote by pgAdmin III. Data were arranged according to a logic of aggregation and stored in a schema with twelve tables. Statistical software was connected to the database directly downloading data from server to local personal computer. RESULTS: There was no problem or anomaly for database implementation and user connections to the database. The epidemiological analysis performed on data stored in the database demonstrated abnormal SPECT findings in 46% of male subjects and 19% of female subjects. Imaging findings suggest that the use of SPECT imaging in our laboratory is appropriate. CONCLUSION: The development of a relational database provides a free software tool for the storage and management of data in line with the current standard.

Impact of inducible ischemia by stress SPECT in cardiac risk assessment in diabetic patients: rationale and design of a prospective, multicenter trial.

BACKGROUND: A prospective, multicenter trial has been designed to evaluate the impact of inducible ischemia by stress single photon emission computed tomography (SPECT) in diabetic patients and to define the role of SPECT in assessing the cardiac risk in such patients. This report presents the details and implications of the Impact of Inducible Ischemia by Stress SPECT (IDIS) trial design. METHODS AND RESULTS: Between January 2002 and September 2005, 1006 consecutive patients (649 men and 357 women; mean age, 63 +/- 9 years) with at least a 5-year history of type 2 diabetes mellitus were enrolled. All patients underwent stress-rest sestamibi SPECT imaging with physical exercise (n = 573) or dipyridamole (n = 433). SPECT studies will be analyzed by use of a 17-segment scoring system to calculate left ventricular ejection fraction, summed stress score, summed rest score, and summed difference score. The SPECT study will be considered abnormal if the summed stress score is 3 or greater. Patients with abnormal studies will be considered to have ischemia if the summed difference score is 2 or greater. CONCLUSION: The results of this trial should help to define the role of SPECT in assessing cardiac risk in diabetic patients. Furthermore, this trial will prospectively evaluate subsequent patient outcome during long-term follow-up.

Infections of the neck leading to descending necrotizing mediastinitis: Role of multi-detector row computed tomography.

Descending necrotizing mediastinitis is an acute, polymicrobial infection of the mediastinum, originating from odontogenic, oropharyngeal and cervical infections. Anatomical continuity of the fascial spaces between the neck and the mediastinum leads to an occasional mediastinal extension of deep neck infection as a serious sequela. An understanding of the anatomy of the deep spaces of the neck and familiarity with the imaging findings in descending necrotizing mediastinitis may allow rapid diagnosis and treatment of this rare and life-threatening complication of deep neck space infection. In this article, we discuss the current role of radiology in diagnosing descending necrotizing mediastinitis, in determining the level of infection and the pathways of spread of infections from the neck to the mediastinum and in planning a successful treatment.

Aspects of spatial memory and behavioral disinhibition in Tg2576 transgenic mice as a model of Alzheimer's disease.

Transgenic mouse models of Alzheimer's disease (AD) have been recently advanced. Tg2576 mice have been shown to develop progressive beta-amyloid (Abeta) neuritic plaques and exhibit impairment of cognitive function. The aim of this study was a better characterization of different aspects of spatial memory performance of transgenic mice, observed at a time when levels of soluble Abeta are elevated and Abeta neuritc plaques start to appear. A general elevation of basal locomotory activity in the home cage was found in Tg2576 mice, which also exhibited an impairment of spontaneous alternation in the Y-maze test. Tg2576 mice were not flexible upon changes in the schedule and failed to codify spatially the testing environment. Consistently, a deficit of spatial memory was also observed when mice were assessed for levels of reactivity to spatial change in the modified open-field test with objects. Compared to controls, Tg2576 mice also exhibited an increased number of explorative approaches to the different objects, and failed to discriminate the displacement of the object. Consistently with the hypothesis of increased disinhibition, a differential behavioural response to the plus-maze paradigm was exhibited by Tg2576 mice. Results clearly indicate that Tg2576 mice are characterized by a number of specific behavioral cognitive alterations, compatible with Alzheimer's disease (AD), which make them a suitable animal model for testing of novel anti-AD drugs.

Incremental prognostic value of stress myocardial perfusion imaging in asymptomatic diabetic patients.

OBJECTIVE: Stress myocardial perfusion single-photon emission computed tomography (MPS) variables are robust estimators of prognosis. No data are available on the comparative ability of stress MPS risk markers using varied iterative and risk classification approaches in asymptomatic diabetic patients. We compared analytical approaches to estimate the added value of MPS variables in estimating coronary artery disease (CAD) outcomes in asymptomatic diabetic patients. We also evaluated the temporal characteristics of cardiac risk according to MPS findings. METHODS: A total of 436 consecutive asymptomatic diabetic patients who underwent stress-rest gated MPS were prospectively enrolled. Multivariable Cox proportional hazards model was employed to estimate cardiac death and nonfatal myocardial infarction (MI). Risk reclassification was calculated and parametric survival analysis was used to predict time to events. RESULTS: At multivariable analysis, post-stress left ventricular ejection fraction (LVEF) and stress MPS ischemia were independent predictors of CAD death or MI (both p < 0.01). The net reclassification improvement by adding MPS results to a model including pre-test CAD likelihood was 0.25 (95% confidence interval 0.06-0.44; p < 0.01). Parametric survival analysis showed the highest probability of CAD death or MI and the major risk acceleration in time in patients with stress MPS ischemia and post-stress LVEF ≤45%. CONCLUSION: In asymptomatic diabetic patients, analytical approaches that establish the reclassification of events may serve for estimation of improved outcomes for stress MPS. Post-stress LVEF and stress-induced ischemia by gated MPS influence the temporal characteristic of the patient's risk at long-term follow-up.