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We compared the prognostic value of myocardial perfusion imaging (MPI) by conventional- (C-) single-photon emission computed tomography (SPECT) and cadmium-zinc-telluride- (CZT-) SPECT in a cohort of patients with suspected or known coronary artery disease (CAD) using machine learning (ML) algorithms. A total of 453 consecutive patients underwent stress MPI by both C-SPECT and CZT-SPECT. The outcome was a composite end point of all-cause death, cardiac death, nonfatal myocardial infarction, or coronary revascularization procedures whichever occurred first. ML analysis performed through the implementation of random forest (RF) and k -nearest neighbors (KNN) algorithms proved that CZT-SPECT has greater accuracy than C-SPECT in detecting CAD. For both algorithms, the sensitivity of CZT-SPECT (96% for RF and 60% for KNN) was greater than that of C-SPECT (88% for RF and 53% for KNN). A preliminary univariate analysis was performed through Mann-Whitney tests separately on the features of each camera in order to understand which ones could distinguish patients who will experience an adverse event from those who will not. Then, a machine learning analysis was performed by using Matlab (v. 2019b). Tree, KNN, support vector machine (SVM), Naïve Bayes, and RF were implemented twice: first, the analysis was performed on the as-is dataset; then, since the dataset was imbalanced (patients experiencing an adverse event were lower than the others), the analysis was performed again after balancing the classes through the Synthetic Minority Oversampling Technique. According to KNN and SVM with and without balancing the classes, the accuracy ( p value = 0.02 and p value = 0.01) and recall ( p value = 0.001 and p value = 0.03) of the CZT-SPECT were greater than those obtained by C-SPECT in a statistically significant way. ML approach showed that although the prognostic value of stress MPI by C-SPECT and CZT-SPECT is comparable, CZT-SPECT seems to have higher accuracy and recall.

Rationale and Objectives PSA density (PSAd), an important decision-making parameter for patients with suspected prostate cancer (PCa), is dependent on magnetic resonance imaging prostate volume (PV) estimation. We aimed to compare the accuracy of the ellipsoid and bullet-shaped formulas with manual whole-gland segmentation as reference standard and to evaluate the corresponding PSAd diagnostic accuracy in predicting clinically significant PCa. Materials and Methods We retrospectively analysed 195 patients with suspected PCa who underwent magnetic resonance imaging and prostate biopsy. Patients with PCa were categorized according to ISUP score. PV and corresponding PSAd were calculated with manual segmentation (mPV and mPSAd) as well as with ellipsoid (ePV and ePSAd) and bullet-shaped (bPV and bPSAd) formulas. Inter and intra-reader reproducibility were assessed with Lin's concordance correlation coefficient and the intraclass correlation coefficient (ICC). A 2-way analysis of variance with post-hoc Bonferroni test was used for assessing PV differences. Predictive values of PSAd calculated with different methods for detecting clinically significant PCa were evaluated by receiver operating characteristic curve analysis and Youden's index. Results Both intra (ρ = 0.99, ICC = 0.99) and inter-reader (ρ = 0.98, ICC = 0.98) reproducibility were excellent. No significant difference was found between ePV and reference standard (p = 1.00). bPV was significantly different from both (p = 0.00). PSAd (mPSAd/ePSAd cut-off ≥ 0.15, bPSAd cut-off ≥ 0.12) had sensitivity = 69–70%, specificity = 72–75%, areas under the curve = 0.757–0.760 (p = 0.70–0.88). Conclusions Our work shows that when using bullet-shaped formula, a different PSAd cut-off must be considered to avoid PCa under-diagnosis and inaccurate risk-stratification.

Background T1 mapping is an established cardiovascular magnetic resonance (CMR) technique that can characterize myocardial tissue. We aimed to determine the weighted mean native T1 values of Anderson-Fabry disease (AFD) patients and the standardized mean differences (SMD) as compared to healthy control subjects. Methods A comprehensive literature search of the PubMed, Scopus and Web of Science databases was conducted according to the PRISMA statement to retrieve original studies reporting myocardial native T1 values in AFD patients and healthy controls. A random effects model was used to calculate SMD, and meta-regression analysis was conducted to explore heterogeneity sources. Subgroup analysis was also performed according to scanner field strength and sequence type. Results From a total of 151 items, 14 articles were included in the final analysis accounting for a total population of 982 subjects. Overall, the weighted mean native T1 values was 984 ± 47 ms in AFD patients and 1016 ± 26 ms in controls (P P = 0.002) and left ventricular hypertrophy (LVH) (P Conclusions Our findings confirm a reduction of native T1 values in AFD patients compared to healthy controls and point out that the degree of T1 shortening in AFD is influenced by gender and LVH. Although T1 mapping is useful in proving cardiac involvement in AFD patients, there is need to standardize shreshold values according to imaging equipment and protocols.

Purpose We assessed the effects of the COVID-19 pandemic on myocardial perfusion imaging (MPI) for ischemic heart disease during the lockdown imposed by the Italian Government. Methods We retrospectively reviewed the number and the findings of stress single-photon emission computed tomography (SPECT)-MPI performed between February and May 2020 during the COVID-19 pandemic at the University of Napoli Federico II. The number and the findings of stress SPECT-MPI studies acquired in the corresponding months of the years 2017, 2018, and 2019 were also evaluated for direct comparison. Results The number of stress SPECT-MPI studies performed during the COVID-19 pandemic (n = 123) was significantly lower (P < 0.0001) compared with the mean yearly number of procedures performed in the corresponding months of the years 2017, 2018, and 2019 (n = 413). Yet, the percentage of abnormal stress SPECT-MPI studies was similar (P = 0.65) during the pandemic (36%) compared with the mean percentage value of the corresponding period of the years 2017, 2018, and 2019 (34%). Conclusion The number of stress SPECT-MPI studies was significantly reduced during the COVID-19 pandemic compared with the corresponding months of the previous 3 years. The lack of difference in the prevalence of abnormal SPECT-MPI studies between the two study periods strongly suggests that many patients with potentially abnormal imaging test have been missed during the pandemic.

Traditional approach for predicting coronary artery disease (CAD) is based on demographic data, symptoms such as chest pain and dyspnea, and comorbidity related to cardiovascular diseases. Usually, these variables are analyzed by logistic regression to quantifying their relationship with the outcome; nevertheless, their predictive value is limited. In the present study, we aimed to investigate the value of different machine learning (ML) techniques for the evaluation of suspected CAD; having as gold standard, the presence of stress-induced ischemia by 82Rb positron emission tomography/computed tomography (PET/CT) myocardial perfusion imaging (MPI) ML was chosen on their clinical use and on the fact that they are representative of different classes of algorithms, such as deterministic (Support vector machine and Naïve Bayes), adaptive (ADA and AdaBoost), and decision tree (Random Forest, rpart, and XGBoost). The study population included 2503 consecutive patients, who underwent MPI for suspected CAD. To testing ML performances, data were split randomly into two parts: training/test (80%) and validation (20%). For training/test, we applied a 5-fold cross-validation, repeated 2 times. With this subset, we performed the tuning of free parameters for each algorithm. For all metrics, the best performance in training/test was observed for AdaBoost. The Naïve Bayes ML resulted to be more efficient in validation approach. The logistic and rpart algorithms showed similar metric values for the training/test and validation approaches. These results are encouraging and indicate that the ML algorithms can improve the evaluation of pretest probability of stress-induced myocardial ischemia.

Anthracyclines are widely used in anticancer protocols, but can induce cardiotoxicity by mechanisms that mainly involve oxidative damage and mitochondrial dysfunction. Radiotherapy can also impair cardiac function by promoting myocardial fibrosis, microvascular damage and decreased density of myocardial capillaries. Hence, we aim at investigating prospectively whether radiotherapy impacts heart function in lymphoma patients who had been already treated with anthracyclines. Twenty-nine consecutive patients with Hodgkin or non-Hodgkin lymphomas underwent echocardiography at baseline (before antineoplastic treatments), and then every two months, until 6 months after treatments completion. Echo evaluation included standard 2D and Speckle Tracking. Twenty-two patients treated with anthracycline-based regimens were eligible. Out of the 22 patients, 8 received chemotherapy only (subgroup 1), while 14 underwent radiotherapy after chemotherapy (subgroup 2). At the end of chemotherapy, ejection fraction was significantly reduced in the whole population. At 6 months after completion of therapies, E/E' increased and Global Longitudinal Strain was compromised in subgroup 2, suggesting additional damage induced by radiotherapy after chemotherapy. On the basis of the data from our small prospective study we can hypothesize that in lymphoma patients anthracyclines can worsen cardiac function, and radiotherapy may have an additional unfavorable myocardial impact.

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 < .05) and ischemic (from 25% to 22%, P < .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 strengths the need to develop more effective strategies for appropriately referring patients to cardiac imaging procedures.

Background Chronotropic incompetence is common in patients with cardiovascular disease and is associated with increased risk of adverse events. We assessed the incremental prognostic value of heart rate reserve (HRR) over stress myocardial perfusion single-photon emission computed tomography (MPS) findings in patients with suspected coronary artery disease (CAD). Methods We studied 866 patients with suspected CAD undergoing exercise stress-MPS as part of their diagnostic program. The primary study endpoint was all-cause mortality. All patients were followed for at least 5 years. HRR was calculated as the difference between peak exercise and resting HR, divided by the difference of age-predicted maximal and resting HR and expressed as percentage. Results During 7 years follow-up, 61 deaths occurred, with a 7% cumulative event rate. Patients experiencing death were older (P < .001), and had a higher prevalence of male gender (P < .001) and diabetes (P < .05). Patients with event also had lower values of HRR (65% ± 27% vs 73% ± 18%, P < .0001) and higher prevalence of stress-induced myocardial ischemia (25% vs 8%, P < .0001). Male gender, HRR and stress-induced ischemia were independent predictors of all-cause mortality (all P < .01). HRR improved the prognostic power of a model including clinical data and MPS findings, increasing the global χ2 from 66 to 82 (P < .005). Conclusions Chronotropic incompetence has independent and incremental prognostic value in predicting all-cause mortality in patients with suspected CAD undergoing exercise stress-MPS. Hence, the evaluation of HRR may further improve patients’ risk stratification.

OBJECTIVE. The purpose of this study was to perform a systematic review and a meta-analysis of diagnostic accuracy studies that used biparametric MRI (bpMRI) for the detection of clinically significant prostate cancer (csPCa). MATERIALS AND METHODS. Multiple medical databases were systematically searched to identify articles using bpMRI for csPCa detection. Sensitivity, specificity, PPV, and NPV were calculated for each study after enough data were extracted to create a 2 × 2 contingency table. Risk of bias was assessed using the QUADAS-2 tool. Meta-analyses based on bivariate random-effects methods were used to calculate pooled sensitivity, specificity, and summary ROC (SROC) curves. A meta-regression analysis was performed to assess heterogeneity sources. RESULTS. A total of 17 studies (3964 patients) that adopted PI-RADS or other scoring systems were included. Sensitivity, specificity, positive likelihood ratio (LR), negative LR, and diagnostic odds ratio of bpMRI in the detection of csPCa were 0.83 (95% CI, 0.76-0.88), 0.71 (95% CI, 0.63-0.79), 2.9 (95% CI, 2.3-3.7), 0.24 (95% CI, 0.17-0.33), and 12 (95% CI, 8-19), respectively, with an area under the SROC curve of 0.84 (95% CI, 0.81-0.87). The overall quality of the included studies was heterogeneous. CONCLUSION. Our results confirm the feasibility of bpMRI for the detection of csPCa and for reducing acquisition time, patient discomfort, and costs. Nevertheless, the available studies proved to be heterogeneous, indicating a need for a more robust validation of this imaging protocol and a standardization of prostate bpMRI acquisition and reporting.

Objectives To explore the impact of sex and age on relationship between prodromal constipation and disease phenotype in Parkinson’s disease at early stages. Methods A total of 385 Parkinson’s disease patients from the PRIAMO study were classified according to the presence of prodromal constipation and followed for 24 months. Multivariable mixed-effect models were applied. All analyses were performed separately for sex (64.1% men) and median age (different by sex: 67 years-old in men and 68 years-old in women). Results As for sex, prodromal constipation was associated with greater odds of attention/memory complaints and apathy symptoms in women only. As for age, prodromal constipation was associated with lower cognitive and higher apathy scores in older patients only. Conclusions Prodromal constipation anticipates lower cognitive performances and more severe apathy since the earliest stages in women and older patients. Sex- and age-related heterogeneity of prodromal markers of Parkinson’s disease may impact disease phenotype.

We assessed the prognostic value of structural abnormalities and coronary vasodilator function in diabetic patients referred to a PET/CT for suspected coronary artery disease (CAD).We studied 451 diabetics and 451 nondiabetics without overt CAD and normal myocardial perfusion. Myocardial blood flow (MBF) was computed from the dynamic rest and stress imaging. Myocardial flow reserve (MFR) was defined as ratio of hyperemic to baseline MBF and was considered reduced when 2.During a mean follow-up of 44 months 33 events occurred. Annualized event rate (AER) was higher in diabetic than nondiabetic patients (1.4% vs 0.3%, P .001). Diabetic patients with reduced MFR had higher AER compared to those with preserved MFR (3.3% vs 0.4%, P .001). At Cox analysis, age, BMI and reduced MFR were independent predictors of events in diabetic patients. Patients with diabetes and reduced MFR had lower event-free survival compared to nondiabetic patients and MFR 2 (P .001). Event-free survival was similar in patients with diabetes and normal MFR and those without diabetes and reduced MFR.Diabetic patients with reduced MFR had higher AER and lower event-free survival compared to those with preserved MFR and to nondiabetic patients.Se evaluó el valor pronóstico de las alteraciones estructurales y la función vasodilatadora coronaria en pacientes diabéticos remitidos a PET/CT por sospecha de enfermedad arterial coronaria (EAC). MéTODOS: Se estudiaron a 451 diabéticos y 451 no diabéticos sin EAC manifiesta y perfusión miocárdica normal. Se calculó el flujo sanguíneo miocárdico (MBF) a partir de las imágenes dinámicas en reposo y estrés. La reserva de flujo miocárdico (MFR) se definió como la relación entre la MBF en hiperemia entre el basal y se consideró reducida al ser2.Durante un seguimiento promedio de 44 meses ocurrieron 33 eventos. La tasa anual de eventos (TAE) fue mayor en los pacientes diabéticos que en los no diabéticos (1.4% frente a 0.3%, P.001). Los pacientes diabéticos con MFR reducido tuvieron una TAE más alta en comparación con aquellos con MFR preservado (3.3% vs 0.4%, P. 001). En el análisis de Cox, la edad, el IMC y el MFR reducido fueron predictores independientes de eventos en pacientes diabéticos. Los pacientes con diabetes y MFR reducido tuvieron una supervivencia libre de eventos más baja en comparación con los pacientes no diabéticos y MFR2 (P. 001). La supervivencia libre de eventos fue similar en pacientes con diabetes y MFR normal y aquellos sin diabetes y MFR reducido.Los pacientes diabéticos con MFR reducido tuvieron una mayor TAE y una menor supervivencia libre de eventos en comparación con aquellos con MFR conservado y con los pacientes no diabéticos.背景:Nous avons évalué la valeur pronostique des anomalies structurelles et de la vasodilatation coronaire chez les patients diabétiques qui nous ont été envoyé pour un examen TEP/TDM pour suspicion de maladie artérielle coronaire (MAC). MéTHODES: Nous avons étudié 451 diabétiques et 451 non-diabétiques sans MAC manifeste et avec une perfusion myocardique normale. Le débit sanguin myocardique (DSM) a été calculé sur bases des images TEP/TDM de repos et de stress. La réserve de perfusion myocardique (RPM) a été définie comme le rapport entre l’hyperémie myocardique et la perfusion myocardique de base et a été considérée comme réduite avec un rapport inferieur à 2. RéSULTATS: Au cours d’un suivi moyen de 44 mois, 33 événements cardiaques ont été enregistrés. Le nombre d’événements cardiaques annualisés (ECA) s’est avéré plus élevé chez les patients diabétiques que chez les patients non diabétiques (1,4% vs 0,3%, P0,001). Les patients diabétiques dont la RPM était réduite ont montré un nombre d’ECA plus élevé que ceux dont la RPM était préservée (3,3% vs 0,4%, P0,001). L’analyse statistique basée sur la méthode Cox a montré que, l’âge, l’IMC et la réduction de la RPM sont des paramètres indépendants chez les patients diabétiques. Les patients atteints de diabète avec une réduction de leur RPM ont eu une survie avec un nombre plus élevés d’événements cardiaques par rapport aux patients non diabétiques avec une RPM inferieure à 2 (P.001). La survie sans événements cardiaques s’est révélée similaire chez les patients atteints de diabète avec une RPM normale et ceux sans diabète avec une RPM réduite.Dans cette étude, les patients diabétiques avec un MFR réduit ont eu une survie entachée d’un nombre plus important d’événements cardiaques par rapport aux diabétiques avec une réserve de perfusion myocardique préservée et aux patients non diabétiques.

Background. We evaluated if risk scores commonly used to predict the absence of significant stenosis at coronary computed tomography (CT) angiography are useful to predict a normal stress myocardial perfusion imaging (MPI) study. Methods. Our cohort included a total of 1422 consecutive patients with zero coronary artery calcium score (ZCS) who underwent 82Rb PET/CT for evaluation of suspected coronary artery disease (CAD). Predictive models were constructed as reported by Genders et al. and Alshahrani et al., and the probability of abnormal summed stress score (SSS) and of reduced myocardial perfusion reserve (MPR) based on these risk scores was assessed. Results. In the overall population, the prevalence of abnormal SSS was 0.10 and the prevalence of reduced MPR was 0.17 (both P < .001). The observed frequencies of abnormal SSS and reduced MPR vs the probabilities predicted by the Genders and Alshahrani models were above the diagonal identity line, highlighting an underestimation of the observed occurrence by these models. The areas under the receiver operating characteristic curve of the Genders and Alshahrani models indicated lack of discriminative ability for predicting abnormal SSS (0.547 and 0.527) and reduced MPR (0.509 and 0.538). The Hosmer–Lemeshow test revealed that both models underestimated the observed occurrence of abnormal SSS and reduced MPR. Conclusions. Available models were unable to identify among patients with ZCS those with a low probability of a normal stress MPI study. Thus, an optimal approach to rule out from MPI patients without detectable coronary calcium still needs to be improved.

Background Biliary atresia (BA) is a rare obliterative cholangiopathy and Kasai portoenterostomy (KP) represents its first-line treatment; clinical and laboratory parameters together with abdominal ultrasound (US) are usually performed during the follow-up. Shear-wave elastography (SWE) is able to evaluate liver parenchyma stiffness; magnetic resonance imaging (MRI) has also been proposed to study these patients. Purpose To correlate US, SWE, and MRI imaging findings with medical outcome in patients with BA who are native liver survivors after KP. Material and Methods We retrospectively enrolled 24 patients. They were divided in two groups based on “ideal” (n = 15) or “non-ideal” (n = 9) medical outcome. US, SWE, and MRI exams were analyzed qualitatively and quantitatively for imaging signs suggestive of chronic liver disease (CLD). Results Significant differences were found in terms of liver surface ( P = 0.007) and morphology ( P = 0.013), portal vein diameter ( P = 0.012) and spleen size ( P = 0.002) by US, liver signal intensity ( P = 0.013), portal vein diameter ( P = 0.010), presence of portosystemic collaterals ( P = 0.042), and spleen size ( P = 0.001) by MRI. The evaluation of portal vein diameter (moderate, κ = 0.44), of portosystemic collaterals (good, κ = 0.78), and spleen size (very good, κ = 0.92) showed the best agreement between US and MRI. A significant ( P = 0.01) difference in liver parenchyma stiffness by SWE was also found between the two groups (cut-off = 9.6 kPa, sensitivity = 55.6%, specificity = 100%, area under the ROC curve = 0.82). Conclusion US, SWE, and MRI findings correlate with the medical outcome in native liver survivor patients with BA treated with KP.

Aims SCN5A is a disease-causing gene associated with familial dilated cardiomyopathy (FDC). We examined the possible association between a common polymorphism in the SCN5A gene (c.1673A>G-p.H558R; rs1805124) and the risk of dilated cardiomyopathy (DCM) occurrence. Methods We genotyped 185 DCM cases (familial DCM, idiopathic DCM and postischemic DCM) and 251 controls for the p.H558R polymorphism in the SCN5A gene, to test the association of the molecular epidemiology of the individuals with the presence/absence of various types of DCM. Results Our results showed that the rs1805124 polymorphism was significantly associated with DCM, and the association was more significant in patients with FDC; furthermore, in these individuals, the less frequent GG genotype was associated with a 7.39-fold increased risk of disease [95% confidence interval (95% CI) = 2.88–18.96; P

Background: We evaluated the warranty period of a normal stress myocardial perfusion single-photon emission computed tomography (MPS) in hypertensive patients. Methods and Results: A total of 471 consecutive hypertensive patients with suspected coronary artery disease and normal perfusion at stress MPS were followed for a mean of 76 ± 21 months. Endpoint events were cardiac death or nonfatal myocardial infarction. With Cox analysis, age (hazard ratio 1.1, P < .005) and stress test type (hazard ratio 2.7, P < .005) were independent predictors of events. With parametric Weibull analysis, patients ≤60 years old undergoing exercise stress test remained at low risk for the entire length of follow-up, while the highest probability of events and the major risk acceleration were observed in those > 60 years old who underwent pharmacologic stress test. In patients undergoing exercise test, peak systolic blood pressure (BP; hazard ratio 1.1, P < .005) emerged as predictor of events, and only subjects with peak systolic BP < 160 mmHg remained at low risk for the entire length of follow-up. In contrast, for patients with peak systolic BP ≥180 mmHg, the time to achieve a cumulative cardiac risk level of 3% was 18 months. Conclusions: In hypertensive patients, the warranty period of a normal stress MPS varies according to stress type and peak systolic BP. A normal stress MPS can be considered reassuring in subjects ≤60 years old who performed exercise stress test and a peak systolic BP < 160 mmHg.

The aim of this study was to investigate the reliability of a novel electrocardiographic (ECG) marker in predicting ventricular arrhythmia (VA) inducibility in individuals with drug-induced Brugada syndrome (BrS) type I pattern. Consecutive patients with drug-induced type I BrS pattern underwent programmed ventricular stimulation (PVS) and, according to their response, were divided into 2 groups. Clinical characteristics and 12-lead ECG intervals before and after ajmaline infusion were compared between the 2 groups. A novel ECG marker named dST-Tiso interval consisting in the interval between the onset of the coved ST-segment elevation and its termination at the isoelectric line was also evaluated. Our cohort included 76 individuals (median age 44 years, 75% male). Twenty-five (32.9%) had VA inducibility requiring defibrillation. As compared with not inducible subjects, those with VA inducibility were more frequently male (92% vs 65%, p = 0.013), had longer PQ interval (basal: 172 vs 152 ms, p = 0.033; after ajmaline: 216 vs 200 ms, p = 0.040), higher J peak (0.6 vs 0.5 mV, p = 0.006) and longer dST-Tiso (360 vs 240 ms, p < 0.001). The dST-Tiso showed a C-statistics of 0.90 (95% confidence interval: 0.82 to 0.99) and an adjusted odds ratio for VA of 1.03 (1.01 to 1.04, p < 0.001). A dST-Tiso interval >300 ms yielded a sensitivity of 92.0%, a specificity of 90.2%, positive and negative predictive values of 82.1% and 95.8%. In conclusion, the dST-Tiso interval is a powerful predictor of VA inducibility in drug-induced BrS type I pattern. External validation is needed, but this marker might be useful in the clinical counseling process of these individuals before invasive PVS.

The purpose of the article is to compare the features of wash-out (WO) parameters between lipid-rich and lipid-poor adrenal adenomas as well as with a group of non-adenoma adrenal lesions. 46 patients (36 F and 10 M, median age 58 years) with unilateral adrenal lesions (35 adenomas, 7 pheochromocytomas, 1 carcinoma, and 3 metastases) were prospectively evaluated; adrenal lesions were divided into adenomas (Group 1) and non-adenomas (Group 2). MR imaging was performed with a 3-Tesla scanner using pre- and post-contrast dedicated sequences. On the basis of the evaluation of qualitative chemical-shift (CS) signal intensity (SI) loss, adrenal adenomas were, respectively, divided in Group 1A (n = 25) as lipid-rich and Group 1B (n = 10) as lipid-poor; non-adenoma adrenal lesions were grouped in Group 2 (n = 11). The following parameters were evaluated: size (mm), CS SI index (%), early (5 min), and delayed (10 min) Relative (R) and Absolute (A) WO values (%). The comparison of AWO and RWO showed significant (p ≤ 0.05) differences between Group 1A and Groups 1B and 2, both using 5- and 10-min images for calculation; conversely, no differences in these dynamic parameters were found between Group 1B and 2; AWO and RWO values were significantly lower in adrenal lesions of Groups 1B and 2 compared to Group 1A, both using 5- and 10-min images for calculation. The quantitative evaluation of WO parameters could not be used to characterize lipid-poor adrenal adenomas for which alternative imaging modalities are required.

Additive manufacturing (commonly referred to as 3D printing) created an attractive approach for regenerative medicine research in musculoskeletal tissue engineering. Given the high number of fabrication technologies available, characterized by different working and physical principles, there are several related risks that need to be managed to protect operators. Recently, an increasing number of studies demonstrated that several types of 3D printers are emitters of ultrafine particles and volatile organic compounds whose harmful effects through inhalation, ingestion and skin uptake are known. Confirmation of danger of these products is not yet final, but this provides a basis to adopt preventive measures in agreement with the precautionary principle. The purpose of this investigation was to provide a useful tool to the researcher for managing the risks related to the use of different kinds of three-dimensional printers (3D printers) in the lab, especiallyconcerning orthopedic applications, and to define appropriate control measures. Particular attention was given to new emerging risks and to developing response strategies for a comprehensive coverage of the health and safety of operators.

PURPOSE: To assess the relationship between coronary atherosclerotic burden and vascular function in diabetic and nondiabetic patients after balancing for coronary risk factors. METHODS: We studied 672 patients without overt coronary artery disease and normal myocardial perfusion on stress 82Rb PET/CT imaging. To account for differences in baseline characteristics between diabetic patients and nondiabetic patients, we created a propensity score-matched cohort considering clinical variables and coronary risk factors. RESULTS: Before matching, diabetic patients had higher coronary artery calcium (CAC) scores (p

Background. Chronotropic response to pharmacological stress test is blunted in patients with autonomic neuropathy. The relationship between heart rate (HR) changes during pharmacological stress test and cardiac autonomic dysfunction has not been fully investigated. We assessed the potential interplay between HR response (HRR) and myocardial innervation in patients with suspected or known coronary artery disease (CAD). Methods and Results. We studied 71 patients with suspected or known CAD referred to pharmacological stress myocardial perfusion imaging and 123I metaiodobenzylguanidine (123IMIBG) cardiac scintigraphy. HRR was calculated as the maximum percent change from baseline according to the formula: (peak HR 2 rest HR)/rest HR 3 100. 123I-MIBG heart-to-mediastinum (H/M) ratio was calculated and a late H/M ratio < 1.6 was considered abnormal. HRR progressively decreased with decreasing late H/M ratio (P for trend = 0.02) and a significant correlation between HRR and late H/M ratio (P = 0.03) was observed. The addition of HRR to a model including age, diabetes, known CAD, left ventricular ejection fraction, and stress-induced ischemia added incremental value in predicting an abnormal late H/M ratio, increasing the global chi-square from 8.09 to 13.8 (P = 0.02). Conclusions. The relationship between HRR and cardiac sympathetic innervation in patients with suspected or known CAD confirms a strong interplay between cardiac response to stress tests and cardiac autonomic activation. This finding suggests that HRR may be used as a surrogate for assessing cardiac sympathetic function.

Cardiac amyloidosis is a restrictive infiltrative cardiomyopathy burdened by high mortality. The two more common forms are immunoglobulin light-chain amyloidosis and transthyretin-related amyloidosis with different prognoses and treatments. However, distinguishing between them is challenging. Appropriate utilization of the different available imaging techniques in the evaluation of patients with known or suspected cardiac amyloidosis is mandatory. We report two cases with cardiac amyloidosis of different etiology and with distinct imaging patterns. In the first case, the negative 99mTc-diphosphonate imaging was useful to support the diagnosis of cardiac amyloid light-chain; the second case emphasized the utility of whole-body scintigraphy in recognizing transthyretin-related cardiac amyloidosis and the potential role of cadmium-zinc-telluride SPECT imaging for the evaluation of segmental distribution of cardiac disease. Both cases support the growing interest in looking for noninvasive methods to type cardiac amyloidosis in the place of invasive myocardial biopsy highlighting both possibilities and limitations of available imaging techniques in diagnosis and treatment monitoring.

Background. The frequency of abnormal stress SPECT myocardial perfusion imaging (MPS) decreased over the past decades despite an increase in the prevalence of cardiovascular risk factors. These findings strengthen the need to develop more effective strategies for appropriately referring patients with suspected coronary artery disease (CAD) to cardiac imaging. The aim of this study was to develop pretest assessment models for predicting abnormal stress MPS. Methods. We included 5,601 consecutive patients with suspected CAD who underwent stress MPS at our academic center. Two different models were considered: a basic model, including age, gender, and anginal symptoms, and a clinical model, including also diabetes, hypertension, hypercholesterolemia, smoking, and family history of CAD. Results. In patients with abnormal MPS, the basic model classified more than 75% of patients as intermediate risk, whereas only 23% were incorrectly classified as low risk. In patients with normal MPS, 45% were correctly classified as low risk and none as high risk. Basic and clinical models had a limited discriminating capacity (area under the receiver operating characteristic curve 0.644 for basic model and 0.647 for clinical model) between individuals with and without abnormal stress MPS. The decision curve analysis demonstrates a high net benefit across a range of threshold probabilities from ~15% to ~30% for both models. Conclusions. A pretest risk stratification based on traditional cardiovascular risk factors has a limited value for predicting an abnormal stress MPS in patients with suspected CAD. However, selecting a proper threshold probability enhance the appropriateness of referral to stress MPS.

BACKGROUND: Coronary artery calcium (CAC) can be used to estimate vascular age in adults, providing a convenient transformation of CAC from Agatston units into a year's scale. We investigated the role of coronary vascular age in predicting stress-induced myocardial ischemia in subjects with suspected coronary artery disease (CAD). METHODS: A total of 717 subjects referred to CAC scoring and 82Rb PET/CT stress-rest myocardial perfusion imaging for suspected CAD were studied. CAC score was measured according to the Agatston method and coronary vascular age by equating estimated CAD risk for chronological age and CAC using the formula 39.1 + 7.25 × ln(CAC + 1). RESULTS: Stress-induced ischemia was present in 105 (15%) patients. Mean chronological age, CAC score, and coronary vascular age were higher (all P < .001) in patients with ischemia compared to those without. At incremental analysis, the global Chi square increased from 41.26 to 68.77 (P < .001) when chronological age was added to clinical variables. Including vascular age in the model, the global Chi square further increased from 68.77 to 106.38 (P < .001). Adding chronological age to clinical data, continuous net reclassification improvement (cNRI) was 0.57, while adding vascular age to clinical data and chronological age cNRI was 0.62. At decision curve analysis, the model including vascular age was associated with the highest net benefit compared to the model including only clinical data, to the model including chronological age and clinical data, and to a strategy considering that all patients had ischemia. The model including vascular age also showed the largest reduction in false-positive rate without missing any ischemic patients. CONCLUSIONS: In subjects with suspected CAD, coronary vascular age is strongly associated with stress-induced ischemia. The communication of a given vascular age would have a superior emotive impact improving observance of therapies and healthier lifestyles.

We measured myocardial blood flow (MBF) and perfusion reserve (MPR) by dynamic CZT-SPECT andTwenty-five patients with available coronary angiography data underwentCZT-SPECT yielded similar baseline MBF, but higher hyperemic MBF and MPR values compared to PET. There was a modest correlation between the two methods for MPR (r = 0.56, P.01). MPR by CZT-SPECT showed a good ability in identify a reduced MPR by PET, with an area under the curve of 0.85. A MPR cut-off of 2.5 was identified by CZT-SPECT for detection of abnormal MPR by PET, with a sensitivity, specificity and accuracy of 86%, 73% and 80%. The area under the curve for the identification of obstructive CAD by regional MPR were 0.83 for CZT-SPECT and 0.84 for PET (P = .90). At CZT-SPECT, a regional MPR of 2.1 provided the best trade-off between sensitivity and specificity for identifying obstructive CAD. Diagnostic accuracy of CZT-SPECT and PET using respective cut-off values was comparable (P = .62).Hyperemic MBF and MPR values obtained by CZT-SPECT are higher than those measured by

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.

BACKGROUND Neuropsychiatric symptoms are common in multiple sclerosis (MS). Among these, apathy is relatively frequent but its relationships with cognitive dysfunctions have been poorly investigated. OBJECTIVE To explore cognitive correlates of apathy with or without depression ("pure apathy") in MS patients. MATERIAL AND METHOD Nondemented MS patients (n = 125), consecutively referred to the Multiple Sclerosis Center of Moscati Hospital, in Avellino, Italy, underwent the Apathy Evaluation Scale Self-Rated (AES-S), the Hamilton Depression Rating Scale (HDRS), and a comprehensive neuropsychological battery. RESULTS According to cut-off scores of AES-S (≥36), of HDRS (≥15) and criteria for diagnosis of apathy and major depression, the sample was divided into 4 subgroups: 49 patients without apathy or depression (A-D-), 20 patients with "pure" apathy (A+D-), 29 patients with depression only (A-D+), and 27 patients with apathy and depression (A+D+). Cognitive performance significantly differed in the 4 groups: in particular MS patients with apathy (A+D- and A+D+) performed significantly worse on executive tasks than patients without apathy, whereas patients with "pure" apathy (A+D-) performed significantly worse than patients without apathy only on executive tasks tapping cognitive control abilities. CONCLUSIONS We found a significant relationship between apathy and dysexecutive defects in MS, consistent with the hypothesis that dysfunctions of prefrontal cortico-subcortical circuits contribute to specific neuropsychiatric syndromes in MS patients. (PsycINFO Database Record

Purpose: Bi-parametric prostate MR (bp-MR) is a valuable tool for detection and characterization of prostate cancer (PCa). Recent studies suggested that PSA-density (PSA-D) in combination with multi-parametric prostate MR as well as bp-MR may achieve a higher diagnostic accuracy than either alone. We aimed to evaluate the diagnostic performance of bp-MR, PSA-D and their combination in biopsy-naïve patients. Methods and materials: We retrospectively analyzed 334 consecutive patients who underwent prostate MR on a 3T scanner. Only patients (n = 114) who underwent TRUS-biopsy within 30 days following MR with no previous prostate biopsies were considered. Our protocol included T2-weighted and DWI sequences. A Likert score based on PI-RADS v2 was used for bp-MR evaluation. Lesions were graded histopathologically using the ISUP score. We assessed three scenarios: detection of lesions independently of ISUP score (ISUP ≥ 1), detection of both intermediate and clinically significant lesions (ISUP ≥ 2) and detection of clinically significant lesions alone (ISUP ≥ 3). Predictive value of bp-MR and PSA-D was evaluated by ROC curves and logistic regression analysis. A p value < 0.05 was considered statistically significant. Results: In all evaluated scenarios, bp-MR showed a significantly higher predictive power (AUC = 0.87-0.95) compared to the performance of PSA-D (AUC = 0.73–0.79), while their combination (AUC = 0.91-0.95) showed no statistically significant improvement compared to bp-MR alone. Conclusion: Our results confirm that bp-MR is a powerful tool in detection of clinically significant PCa. Contrary to findings in the recent literature, PSA-D does not appear to significantly improve its diagnostic performance.

AimsImpaired myocardial perfusion reserve (MPR) may occur earlier than coronary atherosclerosis and it may be an early manifestation of developing coronary artery disease (CAD) in patients with resistant hypertension (RH). We evaluated the relationship between RH and MPR in patients with systemic arterial hypertension after balancing for coronary risk factors.Methods and resultsWe studied 360 subjects without overt CAD and normal myocardial perfusion at stress-rest 82Rb positron emission tomography/computed tomography. To account for differences in baseline characteristics between patients with resistant and controlled hypertension, we created a propensity score-matched cohort considering clinical variables and coronary risk factors. Before matching, patients with RH were significantly older, had higher prevalence of male gender and hypercholesterolaemia, and showed significantly lower global hyperaemic myocardial blood flow (MBF) and MPR compared with those with controlled hypertension, while baseline MBF and coronary artery calcium (CAC) content were similar in both groups. After matching, there were no significant differences in clinical variables and coronary risk factors between patients with resistant and controlled hypertension, but patients with RH still had lower hyperaemic MBF and MPR (both P ConclusionAfter balancing clinical characteristic by propensity score analysis, patients with RH had a blunted hyperaemic MBF and MPR compared with patients with controlled hypertension. The identification of impaired MPR could help to identify early structural alterations of the arterial walls in patients with RH.

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), that 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 protocol 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. Non-cardiac 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 pharmacological 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.

OBJECTIVE: We assessed predictors and temporal characteristics of cardiac risk in patients undergoing stress single-photon emission computed tomography after coronary artery bypass grafting. METHODS: Stress cardiac tomography was performed in 362 patients 5 years after coronary artery bypass grafting. Cardiac death and myocardial infarction were considered as events. Cox proportional hazards analysis was used to identify predictors of events and parametric survival analysis to predict time to events. RESULTS: During a median follow-up of 27 months, 22 cardiac events occurred (6.1% cumulative event rate). At multivariable Cox analysis, ischemia at cardiac tomography (hazards ratio 3.7, 95% confidence interval 1.5-9.1; P = .004), and diabetes (hazards ratio 3.6, 95% confidence interval 1.5-8.5; P = .006) resulted in independent predictors of events. Event-free survival was 96% in patients with normal cardiac tomography, 86% in those with abnormal tomography without ischemia, and 70% in those with (log-rank 10.6, P for trend = .008). The parametric survival model revealed that the cardiac risk was greater for all time intervals and accelerated more over time in patients with ischemia than in those without (chi(2) 21.4, P < .0001). Patients without diabetes and normal cardiac tomography remained below a defined risk level (5%) for the entire follow-up period. CONCLUSION: Stress cardiac tomography performed 5 years after coronary artery bypass grafting is useful to characterize the risk of cardiac events and its temporal variation. Parametric survival model estimates the predicted time to risk and the level of risk at specific time intervals after coronary artery bypass grafting.

Annually, orthopedic residency programs rank and recruit the best possible candidates. Little evidence exists identifying factors that potential candidates use to select their career paths. Recent literature from nonsurgical programs suggests hospital, social and program-based factors influence program selection. We sought to determine what factors influence the choice of an orthopedic career and a candidate's choice of orthopedic residency program.We surveyed medical student applicants to orthopedic programs and current Canadian orthopedic surgery residents (postgraduate year [PGY] 1-5). The confidential online survey focused on 3 broad categories of program selection: educational, program cohesion and noneducation factors. Questions were graded on a Likert Scale and tailed for mean scores.In total, 139 residents from 11 of 17 Canadian orthopedic programs (49% response rate) and 23 medical student applicants (88% response rate) completed our survey. Orthopedic electives and mandatory rotations were reported by 71% of participants as somewhat or very important to their career choice. Collegiality among residents (4.70 ± 0.6), program being the "right fit" (4.65 ± 0.53) and current resident satisfaction with their chosen program (4.63 ±0.66) were ranked with the highest mean scores on a 5-point Likert scale.There are several modifiable factors that residency programs may use to attract applicants, including early availability of clerkship rotations and a strong mentorship environment emphasizing both resident-resident and resident-staff cohesion. Desirable residency programs should develop early access to surgical and operative skills. These must be balanced with a continued emphasis on top-level orthopedic training.Chaque année, les programmes de résidence en orthopédie évaluent et recrutent les meilleurs candidats possibles. On dispose de peu de renseignements au sujet des critères sur lesquels les candidats fondent leur choix de parcours professionnel. Selon la littérature récente issue de programmes non chirurgicaux, les critères de sélection des programmes ont à voir avec les hôpitaux, les programmes eux-mêmes et certains facteurs sociaux. Nous avons voulu savoir quels sont les facteurs qui influent sur le choix d'une carrière en orthopédie et le choix d'un programme de résidence en orthopédie par les candidats.Nous avons interrogé les étudiants en médecine candidats aux programmes d'orthopédie et les médecins résidents actuels en chirurgie orthopédique au Canada (année de résidence [R] de 1 à 5). Le questionnaire en ligne confidentiel portait sur 3 grandes catégories de critères de choix d'un programme : facteurs didactiques, facteurs liés à la cohésion des programmes et facteurs non didactiques. Les questions ont été classées sur une échelle de Likert et les scores moyens ont été estimés.En tout, 139 candidats et médecins résidents actuels de 11 programmes d'orthopédie sur 17 au Canada ont répondu au questionnaire (taux de réponse 49 %). Soixante et onze pour cent des participants ont qualifié les stages électifs et obligatoires en orthopédie de relativement ou très importants pour leur choix de carrière. La collégialité entre les médecins résidents (4,70 ± 0,6), l'adéquation des programmes (4,65 ± 0,53) et la satisfaction actuelle des médecins résidents à l'endroit du programme choisi (4,63 ± 0,66) ont obtenu les scores moyens les plus élevés sur l'échelle de Likert en 5 points.Les programmes de résidence pourraient utiliser plusieurs facteurs modifiables pour attirer des candidats, y compris une offre de stage hâtive et un solide mentorat, mettant l'accent sur la cohésion résident-résident et résident-personnel. Les programmes de résidence attrayants devraient offrir un accès rapide aux compétences chirurgicales et opératoires. Et ces compétences devraient être en phase avec le maintien d'une formation orthopédique de haut niveau.

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.

Cardiac imaging with positron emission tomography/computed tomography (PET/CT) allows measurement of coronary artery calcium (CAC), stress-induced myocardial ischemia and myocardial perfusion reserve (MPR). We evaluated the prognostic role of the combined assessment of regional CAC score, ischemic total perfusion defect (ITPD) and MPR in predicting lesion-related outcome in patients with suspected coronary artery disease (CAD).We studied 206 patients with suspected CAD referred toCompared to vessels without event, those with event showed higher CAC score and ITPD, and lower hyperemic myocardial blood flow and MPR (all p 0.001). At Cox regression multivariable analysis, significant CAD (≥50% stenosis) (p 0.001), CAC score ≥ 300 (p 0.01) and MPR2 (p 0.01) were independent predictors of events. The decision trees analysis for the identification of events produced five terminal nodes. The initial split was on CAC score values. For vessels with CAC300 and MPR ≥2, no further split was performed, while vessels with CAC300 and MPR2 were further stratified by ITPD. For vessels with CAC ≥300 a further stratification was performed only by MPR. The worst prognosis was observed in vessels with CAC ≥300 and MPR2 and in vessels with CAC300, MPR2 and ITPD ≥5%.The combination of CAC score and MPR is useful to predict the lesion-related outcome in the presence of significant CAD.

BACKGROUND: Strain rate is a promising echocardiographic technique which adds further information to that obtained with two-dimensional echocardiography and tissue Doppler imaging (TDI). The present study aimed to evaluate the effects of acute isotonic volume expansion on left ventricular function in patients with idiopathic dilated cardiomyopathy (DCM) utilizing TDI and strain rate measurements. METHODS: Ten patients with DCM and a left ventricular ejection fraction (LVEF) ≤ 40% underwent two-dimensional echocardiography during volume expansion (0.9% NaCl; 0.25 ml/kg/min for 120 min). Peak systolic tissue velocity and peak systolic strain rate were measured at baseline and at the end of volume loading. RESULTS: Mean LVEF was 32 ± 9% at baseline and remained unchanged after volume loading. Similarly, peak systolic velocity was 2.21 cm/s at baseline and remained unchanged after volume expansion. By contrast, peak systolic strain rate significantly reduced from -1.08 ± 0.37/s to -0.76 ± 0.12/s (P < 0.05). CONCLUSIONS: In patients with DCM, peak systolic strain rate significantly reduces with volume loading in the absence of change in LVEF or peak systolic velocities at TDI. Because strain rate is a relative load-independent index of systolic function, the reduction observed is probably related to the decrease in left ventricular systolic performance that follows volume loading in heart failure patients. Thus, peak systolic strain rate appears to be more useful than TDI velocities to evaluate left ventricular dynamics during volume loading in patients with depressed left ventricular function. © 2006 Italian Federation of Cardiology.

Background Cardiac resynchronization therapy (CRT) with multipoint left ventricular (LV) pacing (MultiPoint™ Pacing [MPP], St. Jude Medical) improves acute LV function and LV reverse remodeling at 3 months. Objective The purpose of this study was to test the hypothesis that MPP can also improve LV function at 12 months. Methods Consecutive patients receiving a CRT implant (Unify Quadra MP™ or Quadra Assura MP™ CRT-D and Quartet™ LV lead, St. Jude Medical) were randomized to receive pressure–volume (PV) loop optimized biventricular pacing with either conventional cardiac resynchronization therapy (CONV) or MPP. CRT response was defined by a reduction in end-systolic volume (ESV) ≥15% relative to BASELINE as determined by a blinded observer and alive status. Results Forty-four patients (New York Heart Association class III, ejection fraction [EF] 29% ± 6%, QRS 152 ± 17 ms) were enrolled and randomized to either CONV (N = 22) or MPP (N = 22). During the observation period, 2 patients died of noncardiac causes and 2 patients were lost to follow-up. After 12 months, 12 of 21 patients (57%) in the CONV group and 16 of 21 patients (76%) in the MPP group were classified as CRT responders ( P = .33). ESV reduction and EF increase relative to BASELINE were significantly greater with MPP than with CONV (ESV: median –25%, interquartile range [IQR] [–39% to –20%] vs median –18%, IQR [–25% to –2%], P = .03; EF: median +15%, IQR [8% to 20%] vs median +5%, IQR [–1% to 8%], P Conclusion Sustaining the trend observed 3 months postimplant, PV loop-guided multipoint LV pacing resulted in greater LV reverse remodeling and increased LV function at 12 months compared to PV loop-guided conventional CRT.

Exercise-induced impairment of left ventricular (LV) ejection fraction is common in patients with acromegaly and normal resting systolic function. This study aimed to clarify whether diastolic dysfunction plays a role in the abnormal adaptation to exercise in these patients. Forty-eight patients with active acromegaly underwent LV radionuclide angiography at rest and during exercise. Doppler echocardiography was also performed to assess LV mass index and diastolic function by combined analysis of mitral and pulmonary flow velocity curves. LV ejection fraction at peak exercise was related to rest ejection fraction (r 0.78; P < 0.001), peak filling rate (r 0.55; P < 0.01), LV mass index (r 0.56; P < 0.001), and the difference between duration of diastolic reverse pulmonary vein flow and mitral flow at atrial contraction ( duration) (r 0.54; P < 0.01). At stepwise regression analysis, rest ejection fraction and duration were the only variables that independently influenced (P < 0.001) ejection fraction at peak exercise. Diastolic dysfunction is important in determining cardiac performance during exercise in patients with acromegaly and normal resting systolic function. Combined analysis of pulmonary vein and mitral flow velocity curves allows the identification of impaired LV diastolic function in such patients. (J Clin Endocrinol Metab 88: 4105– 4109, 2003)

BACKGROUND: We investigated the effects of uncoupling protein 3 (UCP3) genetic deletion on (18)F-fluorodeoxyglucose (FDG) cardiac uptake by positron emission tomography (PET)/computed tomography (CT) dedicated animal system after permanent coronary artery ligation. METHODS: Cardiac (18)F-FDG PET/CT was performed in UCP3 knockout (UCP3(-/-)) and wild-type (WT) mice one week after induction of myocardial infarction or sham procedure. RESULTS: In sham-operated mice no difference in left ventricular (LV) volume was detectable between WT and UCP3(-/-). After myocardial infarction, LV volume was higher in both WT and UCP3(-/-) compared to sham animals, with a significant interaction (p < 0.05) between genotype and myocardial infarction. In sham-operated animals no difference in FDG standardized uptake value (SUV) was detectable between WT (1.8 ± 0.6) and UCP3(-/-) (1.8 ± 0.6). After myocardial infarction SUV was significantly higher in remote areas than in infarcted territories in both UCP3(-/-) and WT mice (both p < 0.01). Moreover, in remote areas, SUV was significantly higher (p < 0.001) in UCP3(-/-) as compared to WT, while in the infarcted territory SUV was comparable (p = 0.29). A significant relationship (r = 0.68, p < 0.001) between LV volume and SUV was found. CONCLUSIONS: In a mice model of permanent coronary occlusion, UCP3 deficiency results in a metabolic shift that favored glycolytic metabolism and increased FDG uptake in remote areas.

PURPOSE: Cardiac sympathetic denervation may be detectable in patients with Anderson-Fabry disease (AFD), suggesting its usefulness for early detection of the disease. However, the relationship between sympathetic neuronal damage measured by 123I-metaiodobenzylguanidine (MIBG) imaging with myocardial fibrosis on cardiac magnetic resonance (CMR) is still unclear. METHODS: Cardiac sympathetic innervation was assessed by 123I-MIBG single-photon emission computed tomography (SPECT) in 25 patients with genetically proved AFD. Within one month from MIBG imaging, all patients underwent contrast-enhanced CMR. MIBG defect size and fibrosis size on CMR were measured for the left ventricle (LV) and expressed as %LV. RESULTS: Patients were divided into three groups according to MIBG and CMR findings: (1) matched normal, without MIBG defects and without fibrosis on CMR (n = 10); (2) unmatched, with MIBG defect but without fibrosis (n = 5); and (3) matched abnormal, with MIBG defect and fibrosis (n = 10). The three groups did not differ with respect to age, gender, α-galactosidase, proteinuria, glomerular filtration rate, and troponin I, while New York Heart Association class (p = 0.008), LV hypertrophy (p = 0.05), and enzyme replacement therapy (p = 0.02) were different among groups. Although in patients with matched abnormal findings, there was a significant correlation between MIBG defect size and area of fibrosis at CMR (r2 = 0.98, p < 0.001), MIBG defect size was larger than fibrosis size (26 ± 23 vs. 18 ± 13%LV, p = 0.02). CONCLUSION: Sympathetic neuronal damage is frequent in AFD patients, and it may precede myocardial damage, such as fibrosis. Thus, 123I-MIBG imaging can be considered a challenging technique for early detection of cardiac involvement in AFD.

BACKGROUND: Diabetes mellitus induces structural and functional cardiac alterations that can result in heart failure. Left ventricular (LV) shape is a dynamic component of cardiac geometry influencing its contractile function. However, few data are available comparing LV shape index in diabetic and nondiabetic patients without overt coronary artery disease after balancing for coronary risk factors. METHODS: We studied 1168 patients with normal myocardial perfusion and normal LV ejection fraction on stress gated single-photon emission computed tomography (SPECT) imaging. To account for differences in baseline characteristics between diabetic and nondiabetic patients, we created a propensity score-matched cohort considering clinical variables, coronary risk factors, and stress type. RESULTS: Before matching, diabetic patients were older, had higher prevalence of male gender and coronary risk factors, and higher end-diastolic and end-systolic LV shape index. After matching, all clinical characteristics were comparable between diabetic and nondiabetic patients, but diabetic patients still had higher end-diastolic and end-systolic LV shape index (both P < .001). At multivariable linear regression analysis, diabetes was a strong predictor of end-systolic LV shape index in the overall study population and in the propensity-matched cohort. CONCLUSIONS: Diabetic patients have higher values of LV shape index compared to nondiabetic patients also after balancing clinical characteristics by propensity score analysis. Shape indexes assessment by gated SPECT may be useful for identifying early LV remodeling in patients with diabetes.

PURPOSE: To evaluate the prognostic value of coronary atherosclerotic burden, assessed by coronary artery calcium (CAC) score, and coronary vascular function, assessed by coronary flow reserve (CFR) in patients with suspected coronary artery disease (CAD). METHODS: We studied 436 patients undergoing hybrid 82Rb positron emission tomography/computed tomography imaging. CAC score was measured according to the Agatston method, and patients were categorized into three groups (0

However, improving nuclear cardiology practiceis required to maximize its role in the presence ofmultiple concurrent imaging modalities.REGADENOSON SPECT MYOCARDIALPERFUSION IMAGINGThe United States Food and Drug Administrationapproved the use of regadenoson, a selective adenosineA2A receptor agonist, on April 10, 2008 for SPECTmyocardial perfusion imaging as vasodilator stressagent.

Purpose The Prostate Imaging-Reporting and Data System has been developed to standardize prostate MRI in terms of acquisition, interpretation and reporting. It received a major revision in late 2014 (PI-RADSv2). Recently, doubts have been raised on imaging facilities adherence to its acquisition protocol. With this systematic review, we assessed adherence to PI-RADSv2 minimum technical specifications in literature, to achieve a better understanding of issues limiting their diffusion. Method Multiple medical literature databases were extensively searched to retrieve original studies published after January 2016 performing prostate MRI. Information pertaining acquisition protocols and patient enrolment were recorded for analysis. Technical parameters were dichotomized in relation to adherence to the corresponding minimal technical requirements. Results A total of 150 studies were included for analysis. Only 5% reported every technical parameter specified in the PI-RADSv2 document requirements, none of which completely met guideline specifications. Overall, 19% were in line with PI-RADSv2 for all reported MRI acquisition parameters. The adherence was lowest for T2-weighted frequency in-plane resolution (12%), diffusion-weighted imaging field of view (40%), apparent diffusion coefficient map low b-value (27%) and dynamic contrast-enhanced imaging temporal resolution (43%). Considering its role in image interpretation, it must be highlighted that only 59% of studies reporting diffusion-weighted imaging high b-value follow recommendations. Conclusions Adherence to PI-RADSv2 minimum technical standards is heterogeneous in the scientific community. Our findings endorse the need for greater diffusion of PI-RADSv2 guidelines to achieve protocol standardization and support the notion that some requirements might benefit from streamlining to improve clinical applicability.

Apathy is a state of diminished goal-directed speech, motor activity and emotions. The prevalence of apathy in Parkinson's disease (PD) ranges from 16 to 62%. Several studies have investigated the relationships between apathy and other dimensions of PD, but little is known about possible discrepancies between self-evaluation (SE) and caregiver reporting (CR) of this symptom. The aim of this study is twofold: 1) to investigate the differences in apathy evaluations according to the point of view from which apathy is reported (SE vs CR); 2) to identify the possible relationships between each of the two evaluations (SE and CR) and cognitive and affective dimensions of PD. Forty-eight patients with PD were assessed using the Apathy Evaluation Scale (AES) in its SE and CR versions (AES-SE and AES-CR); cognitive, affective and behavioral symptoms were also assessed. AES-SE scores were significantly higher than AESCR ones. Neither AES version correlated with depression, whereas both correlated with motor impairment, disease stage and behavioral symptoms. Mini-Mental State Examination and Frontal Assessment Battery scores showed significant negative correlations only with AES-SE scores. Our findings suggest that the point of view from which apathy is seen can lead to significant discrepancies, even when using the same tool. This should be taken into account in order to obtain correct assessment of this disabling and distressing symptom.

Silent myocardial ischemia is defined as objective documentation of myocardial ischemia in the absence of angina or anginal equivalents. The first description of silent ischemia date to the 1970s, but despite intensive investigation, its pathophysiology, detection, prevalence, and clinical significance are still debated. The need and the benefit of treating silent ischemia, particularly in patients without history of coronary artery disease (CAD) and who are asymptomatic, remain questionable. Asymptomatic (silent) myocardial ischemia may be identified during routine daily activities or during stress testing in patients without or with known CAD. One of the earliest investigations addressing the prevalence and significance of silent myocardial ischemia in asymptomatic subjects is the United States Air Force study, conducted in 1,390 men, 111 of whom had positive exercise tests. Thirty-four of these 111 (about 2.5% of the total) had coronary artery lesions of at least 50% stenosis. Thaulow et al studied 2014 Norwegian male office workers between 40 and 59 years of age (mean age 50 year). Coronary angiography in men with positive exercise tests demonstrated that 69 had stenoses of 50% or greater in one coronary artery; 50 of these (2.7% of the total) patients were completely asymptomatic, a percentage similar to that found in the United States Air Force study. He et al reported in nearly 4,000 subjects studied, that the severity of coronary artery calcification by electron-beam computed tomography (CT) can predict silent myocardial ischemia on stress single-photon emission computed tomography (MPS). Silent myocardial ischemia was present in 2.6% of patients with coronary calcium score between 11 and 100, 11.3% of patients with scores between 101 and 399, and 46% of patients with scores above 400. In this issue of the Journal, Malhotra et al evaluated the relationship between silent myocardial ischemia and CAD risk factors in a retrospective analysis of 1,354 asymptomatic patients without known CAD referred for stress MPS. The most common reasons for referral of these patients without chest pain or dyspnea were CAD risk factors, atrial fibrillation, and pre-operative evaluation. As expected, the prevalence of silent myocardial ischemia in these asymptomatic subjects was very low (7.2%). The authors identified a positive relationship between the number of CAD risk factors and the prevalence of silent myocardial ischemia. However in older patients ([74 years), who had a significantly greater prevalence of silent ischemia, the presence and number of risk factors were not predictive. The positive predictive value of an abnormal MPS for predicting angiographic CAD was only 53% and, among all asymptomatic patients referred for stress MPS, significant anatomical CAD was found in only 31 of 1,354 (2%) patients. Malhotra et al concluded that their findings support current guidelines, which generally advocate against routine testing in asymptomatic patients. Unfortunately, they did not provide outcome information for these patients, in particular for the 60 patients (4.4% of overall study population) defined to have ‘‘prognostically significant ischemia’’ (i.e., [10% of left ventricular myocardium). Previous studies have found that silent myocardial ischemia detected in healthy individuals without known CAD has been shown to predict adverse events. The Lipid Research Clinic’s Coronary Primary Prevention Trial (LRCPPT) and the Multiple Risk Factor Intervention Trial (MRFIT) showed that the presence of asymptomatic myocardial ischemia detected during baseline treadmill exercise testing in subjects without known CAD predicted a more than fivefold increased risk of coronary events and cardiac death during the 7to 10-year follow-up period. Other studies evaluated From the Department of Translational Medical Sciences, University Federico II, Institute of Diagnostic and Nuclear Development, SDN Foundation; and Department of Advanced Biomedical Sciences, University Federico II, Naples, Italy. Reprint requests: Alberto Cuocolo, MD, Department of Advanced Biomedical Sciences, University Federico II, Via Pansini 5, 80131 Naples, Italy; cuocolo@unina.it. J Nucl Cardiol 2013;20:707–10. 1071-3581/$34.00 Copyright 2013 American Society of Nuclear Cardiology. doi:10.1007/s12350-013-9725-z

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. 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

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 2 7.7, p 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.

PURPOSE: Imaging of the cardiac autonomic system with (123)I-metaiodobenzylguanidine (MIBG) is useful in the evaluation of patients with a variety of cardiac conditions, including heart failure (HF), but few data are available about the reproducibility of this technique. We assessed the observer reproducibility of the results from a low-dose (123)I-MIBG cardiac imaging protocol in patients with HF. METHODS: A total of 74 patients (62 men, age 67 ± 10 years) with HF and left ventricular systolic dysfunction (ejection fraction 31 ± 7 %) underwent low-dose (111 MBq) planar and single-photon emission computed tomography (SPECT) (123)I-MIBG cardiac sympathetic imaging. The intraclass coefficient of correlation (ICC), Lin's concordance correlation coefficient, and Bland-Altman analysis were used to evaluate the intraobserver and interobserver reproducibility of early and late heart-to-mediastinum (H/M) ratios and of defect scores on SPECT images. The ? statistic was used to evaluate the concordance rates for the identification of patients with a low H/M ratio (0.90) for all measurements. For the identification of patients with a low H/M ratio, the ? values were 0.90 for intraobserver concordance and 0.83 for interobserver concordance. CONCLUSION: The present study showed a high observer reproducibility of planar H/M ratios and SPECT defect scores using a low-dose (123)I-MIBG cardiac imaging protocol in patients with HF.

Background— We prospectively evaluated the incremental prognostic value of transient ischemic dilation (TID) in patients with type 2 diabetes mellitus during long-term follow-up and estimated cardiac death and nonfatal myocardial infarction (MI) using traditional approaches of prognostication to more recent methods. Methods and Results— A total of 672 consecutive diabetic patients with available rest and stress gated myocardial perfusion single-photon emission computed tomographic data were enrolled. Stepwise Cox regression analysis was used to estimate cardiac death or nonfatal MI. Risk reclassification was calculated, and an exploratory analysis was performed to evaluate the effect of coronary revascularization on event-free survival. Adding TID to a multivariable model, including age, history of MI, stress type, poststress left ventricular ejection fraction, and stress-induced myocardial ischemia, improved discrimination of cardiac death or nonfatal MI (C statistic, 0.74–0.82; P =0.01; adjusted hazard ratio, 3.6; P P P Conclusions— TID provides independent and incremental prognostic information for the prediction of cardiac death or nonfatal MI in patients with diabetes mellitus. The addition of TID to a prediction model based on cardiovascular risk factors, left ventricular ejection fraction, and ischemia significantly improves risk discrimination and reclassification for incident cardiac events. The effect of revascularization seems to be influenced by left ventricular systolic function, stress-induced myocardial ischemia, and TID.

BACKGROUND: This study assessed the reproducibility and accuracy of 2-deoxy-2[(18)F]fluoro-D: -glucose ((18)F-FDG) for non-invasive quantification of myocardial infarct size in mice by a high-resolution positron emission tomography (PET)/computed tomography (CT) system. METHODS AND RESULTS: Mice were studied by (18)F-FDG PET/CT 1 week after induction of myocardial infarction by permanent coronary occlusion or sham procedure. In a subset of mice, PET/CT was repeated 2 days apart to assess the reproducibility of infarct size measurements. Histological analysis was used as reference method to validate imaging data. The average difference in infarct size measurements between the first and the second study was -0.42% ± 2.07% (95% confidence interval -2.6 to 1.75) with a repeatability coefficient of 4.05%. At Bland-Altman analysis, the lower and upper limits of agreement between the two repeated studies were -4.46% and 3.63%, respectively, and no correlation between difference and mean was found (P = .89). The concordance correlation coefficient was 0.99 (P < .001) and the intraclass coefficient of correlation was 0.99. A high correlation between PET/CT and histology was found for measurement of infarct size (P < .001). Using Bland-Altman analysis, the mean difference in infarct size measurement (PET/CT minus histology) was 1.9% (95% confidence interval 0.94% to 2.86%). CONCLUSIONS: In a mice model of permanent coronary occlusion non-invasive measurement of infarct size with high-resolution (18)F-FDG, PET/CT has excellent reproducibility and accuracy. These findings support the use of this methodology in serial studies.