Additional prognostic impact of plaque characterization with on-site CT-derived fractional flow Reserve in Coronary CT angiography.

BACKGROUND: On-site computed tomography-derived fractional flow reserve (CT-FFR) is a feasible method for examining lesion-specific ischemia, and plaque analysis of coronary CT angiography (CCTA) is useful for predicting future cardiac events. However, their utility and association on a per-vessel level remain unclear. METHODS: We analyzed vessels showing 50-90 % stenosis on CCTA where planned revascularization was not performed after CCTA within 90 days. Relevant features, including CT-FFR and the plaque burden [necrotic core to the total plaque volume (% necrotic core), and non-calcified plaque (NCP) to vessel volume (% NCP)] using a novel algorithm for analyzing plaque to predict vessel-oriented composite outcomes (VOCO), including cardiac death, non-fatal myocardial infarction, and unplanned vessel-related revascularization, were assessed. RESULTS: In 256 patients (68.7 ±â€¯9.4 years; 73.8 % male) with 354 vessels (10.5 % CT-FFR ≤0.80), VOCO occurred in 24 vessels (6.8 %) during a median follow-up of 3.6 years. Multivariable Cox analysis revealed CT-FFR ≤0.80 had the pronounced impact on VOCO, and moreover, higher % necrotic core and % NCP were independently associated with VOCO [adjusted hazard ratio 3.43 (95 % confidence interval 1.42-8.29) and 4.05 (1.19-13.71), respectively], especially for vessels with CT-FFR >0.80. CONCLUSIONS: In vessels without planned revascularization, per-vessel CT-FFR ≤0.80 was the notable predictor of future cardiac events. Additionally, necrotic core volume and NCP were identified as independent predictors along with CT-FFR.

Oxytocin-induced increases in cytokines and clinical effect on the core social features of autism: Analyses of RCT datasets.

Although oxytocin may provide a novel therapeutics for the core features of autism spectrum disorder (ASD), previous results regarding the efficacy of repeated or higher dose oxytocin are controversial, and the underlying mechanisms remain unclear. The current study is aimed to clarify whether repeated oxytocin alter plasma cytokine levels in relation to clinical changes of autism social core feature. Here we analyzed cytokine concentrations using comprehensive proteomics of plasmas of 207 adult males with high-functioning ASD collected from two independent multi-center large-scale randomized controlled trials (RCTs): Testing effects of 4-week intranasal administrations of TTA-121 (A novel oxytocin spray with enhanced bioavailability: 3U, 6U, 10U, or 20U/day) and placebo in the crossover discovery RCT; 48U/day Syntocinon or placebo in the parallel-group verification RCT. Among the successfully quantified 17 cytokines, 4 weeks TTA-121 6U (the peak dose for clinical effects) significantly elevated IL-7 (9.74, 95 % confidence interval [CI] 3.59 to 15.90, False discovery rate corrected P (PFDR) < 0.001), IL-9 (56.64, 20.46 to 92.82, PFDR < 0.001) and MIP-1b (18.27, 4.96 to 31.57, PFDR < 0.001) compared with placebo. Inverted U-shape dose-response relationships peaking at TTA-121 6U were consistently observed for all these cytokines (IL-7: P < 0.001; IL-9: P < 0.001; MIP-1b: P = 0.002). Increased IL-7 and IL-9 in participants with ASD after 4 weeks TTA-121 6U administration compared with placebo was verified in the confirmatory analyses in the dataset before crossover (PFDR < 0.001). Furthermore, the changes in all these cytokines during 4 weeks of TTA-121 10U administration revealed associations with changes in reciprocity score, the original primary outcome, observed during the same period (IL-7: Coefficient = -0.05, -0.10 to 0.003, P = 0.067; IL-9: -0.01, -0.02 to -0.003, P = 0.005; MIP-1b: -0.02, -0.04 to -0.007, P = 0.005). These findings provide the first evidence for a role of interaction between oxytocin and neuroinflammation in the change of ASD core social features, and support the potential role of this interaction as a novel therapeutic seed. Trial registration: UMIN000015264, NCT03466671/UMIN000031412.

Characteristics of goal-setting tools in adult rehabilitation: A scoping review.

OBJECTIVES: This scoping review aims to map the literature on goal-setting tools in adult rehabilitation, exploring their characteristics, target users and supporting evidence to inform practice and future research in this area. METHODS: We completed a comprehensive search of four databases to identify relevant articles on tools for goal setting in rehabilitation. We followed Arkey and O'Malley's scoping review process to guide article selection, data extraction and data analysis. RESULTS: We identified a total of 165 studies that reported on 55 different goal-setting tools, including tools for goal selection and goal documentation (n = 31), goal setting and intervention planning (n = 15), and for measuring the quality of the goal-setting process (n = 9). Over half of the tools were primarily designed for use in rehabilitation of physical disabilities (n = 32). Some tools fell under multiple sub-categories based on their characteristics as follows: 22 framework tools, 12 interview tools, 9 outcome measurement tools for goal achievement, 6 outcome measurement tools for goal quality and 25 documentation tools. The majority of goal-setting instruments targeted goals at the level of activity and participation (n = 51) and aimed to facilitate a client-centred or shared decision-making approach to rehabilitation planning (n = 46). CONCLUSIONS: This study provides a comprehensive overview of existing goal-setting tools, highlighting their characteristics, target users and identified needs. These findings can enhance practitioners' awareness of the range of goal-setting tools available and can enable more effective utilization of these tools in clinical practice. Further research should investigate how clinicians can combine multiple tools to deliver goal setting.

Fully automated coronary artery calcium quantification on electrocardiogram-gated non-contrast cardiac computed tomography using deep-learning with novel Heart-labelling method.

Aims: To develop an artificial intelligence (AI)-model which enables fully automated accurate quantification of coronary artery calcium (CAC), using deep learning (DL) on electrocardiogram (ECG)-gated non-contrast cardiac computed tomography (gated CCT) images. Methods and results: Retrospectively, 560 gated CCT images (including 60 synthetic images) performed at our institution were used to train AI-model, which can automatically divide heart region into five areas belonging to left main (LM), left anterior descending (LAD), circumflex (LCX), right coronary artery (RCA), and another. Total and vessel-specific CAC score (CACS) in each scan were manually evaluated. AI-model was trained with novel Heart-labelling method via DL according to the manual-derived results. Then, another 409 gated CCT images obtained in our institution were used for model validation. The performance of present AI-model was tested using another external cohort of 400 gated CCT images of Stanford Center for Artificial Intelligence of Medical Imaging by comparing with the ground truth. The overall accuracy of the AI-model for total CACS classification was excellent with Cohen's kappa of k = 0.89 and 0.95 (validation and test, respectively), which surpasses previous research of k = 0.89. Bland-Altman analysis showed little difference in individual total and vessel-specific CACS between AI-derived CACS and ground truth in test cohort (mean difference [95% confidence interval] were 1.5 [-42.6, 45.6], -1.5 [-100.5, 97.5], 6.6 [-60.2, 73.5], 0.96 [-59.2, 61.1], and 7.6 [-134.1, 149.2] for LM, LAD, LCX, RCA, and total CACS, respectively). Conclusion: Present Heart-labelling method provides a further improvement in fully automated, total, and vessel-specific CAC quantification on gated CCT.

Coronary Artery Vorticity to Predict Functional Plaque Progression in Participants with Type 2 Diabetes Mellitus.

Purpose: To investigate whether vorticity could predict functional plaque progression better than high-risk plaque (HRP) and lesion length (LL) in individuals with type 2 diabetes mellitus. Materials and Methods: This single-center prospective study included 61 participants (mean age, 61 years ± 9 [SD]; 43 male participants) who underwent serial coronary CT angiography at 2 years, with 20%-70% stenosis at initial CT between October 2015 and March 2020. The number of the following HRP characteristics was recorded: low attenuation, positive remodeling, spotty calcification, and napkin-ring sign. Vorticity was calculated using a mesh-free simulation. A decrease in CT fractional flow reserve larger than 0.05 indicated functional progression. Models using HRP and LL and vorticity were compared using receiver operating characteristic curve analysis. Results: Of the 94 vessels evaluated, 25 vessels (27%) showed functional progression. Vessels with functional progression showed higher vorticity at distal stenosis (984 sec-1; IQR: 730-1253 vs 443 sec-1; IQR: 295-602; P < .001) than vessels without progression. The area under the receiver operating characteristic curve of vorticity (0.91; 95% CI: 0.84, 0.97) was higher than that of HRP and LL (0.69; 95% CI: 0.56, 0.82; P < .01). Diagnostic accuracy of vorticity (85%; 80 of 94 vessels; 95% CI: 76, 92) was higher than that of HRP and LL (72%; 68 of 94 vessels; 95% CI: 62, 81; P = .004). Conclusion: In participants with type 2 diabetes mellitus, vorticity at distal stenosis was a better predictor of functional plaque progression than HRP and LL.Keywords: Coronary Artery, Vorticity, Functional Plaque Progression, Type 2 Diabetes, Vasculature, CT Angiography, Computational Fluid Dynamics, Fractional Flow Reserve Supplemental material is available for this article. © RSNA, 2023.

First validation of stress myocardial perfusion scintigraphy using a novel reconstruction process.

BACKGROUND: A new image reconstruction process termed the MUS method (masking process on unsmoothed images) was developed to eliminate artifacts, especially those in the inferior wall. We compared diagnostic performance between the MUS and conventional method in stress myocardial perfusion SPECT (MPS). METHODS: Enrolled were 126 patients who underwent stress-rest MPS with 99 m Tc-MIBI. Patients were divided into two groups: 91 with < 50% stenosis in the RCA or LCX (non-ischemia group) and 35 patients with ≥ 90% stenosis or FFR-positive in the RCA (ischemia group), according to coronary CT or coronary angiography within 3 months of MPS. Ischemic heart disease (IHD) was considered positive when the summed difference score of five segments corresponding to the inferior wall region was ≥ 2. RESULTS: Sensitivity was comparable between the MUS method and the conventional method (ordered subset expectation maximization; OSEM) (51% vs 54%, respectively; (p = 0.366), specificity was significantly higher using the MUS method (87% vs 77%, respectively; p < 0.05), and diagnostic performance was higher using the MUS method (area under curve [AUC], conventional 0.61 vs. MUS 0.69, p = 0.138). In evaluation of 87 patients after excluding 39 who received additional prone imaging, sensitivity using the MUS method was 44%, which was comparable to 44% using the conventional method but specificity was 90%, which was significantly higher than 77% using the conventional method (p < 0.05). The diagnostic performance of the MUS method was higher (AUC, conventional 0.60 vs. MUS 0.67, p = 0.185). CONCLUSION: Use of the MUS method improved specificity in diagnosis of IHD while maintaining sensitivity, compared with the conventional method. The MUS method can achieve an improvement in diagnostic accuracy equivalent to the supine position, particularly in patients who have difficulty performing the prone position, without increasing the patient burden.

1H-MRS to evaluate improved triglyceride accumulation in idiopathic triglyceride deposit cardiomyovasculopathy after CNT-01 (tricaprin/trisdecanion) administration.

Summary: Triglyceride deposit cardiomyovasculopathy (TGCV) is an intractable disease characterized by massive triglyceride (TG) accumulation in the myocardium and coronary arteries caused by genetic or acquired dysfunction of adipose TG lipase (ATGL). A phase IIa trial has been conducted involving patients with idiopathic TGCV using CNT-01 (tricaprin/trisdecanion) by the Japan TGCV study group, which showed that CNT-01 improved myocardial lipolysis as demonstrated by iodine-123-beta-methyl iodophenyl-pentadecanoic acid (BMIPP) scintigraphy. We evaluated changes in myocardial TG content using proton magnetic resonance spectroscopy (1H-MRS) before/after CNT-01. This report describes a male patient with hypertension, diabetes, angina pectoris, repeated percutaneous coronary intervention, chest pain, and exertional dyspnea that persisted despite standard medications and nitroglycerin. Idiopathic TGCV was diagnosed based on a remarkably reduced washout rate (WR) for BMIPP scintigraphy, high myocardial TG content on 1H-MRS, and no ATGL mutation. After an 8-week, 1.5 g/day CNT-01 administration, the WR of BMIPP increased from 5.1 to 13.3% and the myocardial TG content decreased from 8.4 to 5.9%, with no adverse effects. CNT-01 corrected myocardial lipolysis and subsequently reduced TG content in idiopathic TGCV as evaluated using 1H-MRS, which may be a useful, noninvasive evaluation of therapeutic efficacy. Learning points: Triglyceride deposit cardiomyovasculopathy (TGCV) is an intractable disease characterized by massive triglyceride accumulation in the myocardium and coronary arteries, caused by genetic or acquired dysfunction of adipose triglyceride lipase. Japan TGCV Study Group developed a specific treatment for idiopathic TGCV using CNT-01 (tricaprin/trisdecanion), a type of medium-chain fatty acid. CNT-01 corrected myocardial lipolysis and reduced TG content in idiopathic TGCV using proton magnetic resonance spectroscopy, which may be a useful noninvasive evaluation of therapeutic efficacy.

Validation and clinical impact of novel pericoronary adipose tissue measurement on ECG-gated non-contrast chest CT.

BACKGROUND AND AIMS: We aimed to develop a method for quantifying pericoronary adipose tissue (PCAT) on electrocardiogram (ECG)-gated non-contrast CT (NC-PCAT) and validate its efficacy and prognostic value. METHODS: We retrospectively studied two independent cohorts. PCAT was quantified conventionally. NC-PCAT was defined as the mean CT value of epicardial fat tissue adjacent to right coronary artery ostium on ECG-gated non-contrast CT. In cohort 1 (n = 300), we evaluated the correlation of two methods and the association between NC-PCAT and CT-verified high-risk plaque (HRP). We dichotomized cohort 2 (n = 333) by the median of NC-PCAT, and assessed the prognostic value of NC-PCAT for primary endpoint (all-cause death and non-fatal myocardial infarction) by Cox regression analysis. The median duration of follow-up was 2.9 years. RESULTS: NC-PCAT was correlated with PCAT (r = 0.68, p<0.0001). In multivariable logistic regression analysis, high NC-PCAT (OR:1.06; 95%CI:1.03-1.10; p = 0.0001), coronary artery calcium score (CACS) (OR:1.01 per 10 CACS increase, 95%CI:1.00-1.02; p = 0.013), and current smoking (OR:2.58; 95%CI:1.03-6.49; p = 0.044) were independent predictors of HRP. Among patients with CACS>0 (n = 193), NC-PCAT (OR:1.06; 95%CI:1.03-1.10; p = 0.0002), current smoking (OR:3.02; 95%CI:1.17-7.82; p = 0.027), and male sex (OR:2.81; 95%CI:1.06-7.48; p = 0.028) were independent predictors of HRP, whereas CACS was not (p = 0.15). Multivariable Cox regression analysis revealed high NC-PCAT as an independent predictor of the primary endpoint, even after adjustment for sex and age (HR:4.3; 95%CI:1.2-15.2; p = 0.012). CONCLUSIONS: There was a positive correlation between NC-PCAT and PCAT, with high NC-PCAT significantly associated with worse clinical outcome (independent of CACS) as well as presence of HRP.

Relationship between coronary high-intensity plaques on T1-weighted imaging by cardiovascular magnetic resonance and vulnerable plaque features by near-infrared spectroscopy and intravascular ultrasound: a prospective cohort study.

BACKGROUND: This study aimed to compare the coronary plaque characterization by cardiovascular magnetic resonance (CMR) and near-infrared spectroscopy (NIRS)-intravascular ultrasound (IVUS) (NIRS-IVUS), and to determine whether pre-percutaneous coronary intervention (PCI) evaluation using CMR identifies high-intensity plaques (HIPs) at risk of peri-procedural myocardial infarction (pMI). Although there is little evidence in comparison with NIRS-IVUS findings, which have recently been shown to identify vulnerable plaques, we inferred that CMR-derived HIPs would be associated with vulnerable plaque features identified on NIRS-IVUS. METHODS: 52 patients with stable coronary artery disease who underwent CMR with non-contrast T1-weighted imaging and PCI using NIRS-IVUS were studied. HIP was defined as a signal intensity of the coronary plaque-to-myocardial signal intensity ratio (PMR) ≥ 1.4, which was measured from the data of CMR images. We evaluated whether HIPs were associated with the NIRS-derived maximum 4-mm lipid-core burden index (maxLCBI4mm) and plaque morphology on IVUS, and assessed the incidence and predictor of pMI defined by the current Universal Definition using high-sensitive cardiac troponin-T. RESULTS: Of 62 lesions, HIPs were observed in 30 lesions (48%). The HIP group had a significantly higher remodeling index, plaque burden, and proportion of echo-lucent plaque and maxLCBI4mm ≥ 400 (known as large lipid-rich plaque [LRP]) than the non-HIP group. The correlation between the maxLCBI4mm and PMR was significantly positive (r = 0.51). In multivariable logistic regression analysis for prediction of HIP, NIRS-derived large LRP (odds ratio [OR] = 5.41; 95% confidence intervals [CIs] 1.65-17.8, p = 0.005) and IVUS-derived echo-lucent plaque (OR = 5.12; 95% CIs 1.11-23.6, p = 0.036) were strong independent predictors. Furthermore, pMI occurred in 14 of 30 lesions (47%) with HIP, compared to only 5 of 32 lesions (16%) without HIP (p = 0.005). In multivariable logistic regression analysis for prediction of incidence of pMI, CMR-derived HIP (OR = 5.68; 95% CIs 1.53-21.1, p = 0.009) was a strong independent predictor, but not NIRS-derived large LRP and IVUS-derived echo-lucent plaque. CONCLUSIONS: There is an important relationship between CMR-derived HIP and NIRS-derived large LRP. We also confirmed that non-contrast T1-weighted CMR imaging is useful for characterization of vulnerable plaque features as well as for pre-PCI risk stratification. Trial registration The ethics committee of Juntendo Clinical Research and Trial Center approved this study on January 26, 2021 (Reference Number 20-313).

Dual-energy CT imaging of atherosclerotic plaque using novel ultrasmall superparamagnetic iron oxide in hyperlipidemic rabbits.

BACKGROUND: A study using magnetic resonance imaging (MRI) revealed that ultra-small superparamagnetic iron oxide is phagocytosed by macrophages. However, MRI has limitations in obtaining clear images due to its poor spatial and temporal resolutions. PURPOSE: To examine whether the use of dual-energy computed tomography (DECT) facilitated the visualization of carboxymethyl-diethylaminoethyl dextran magnetite ultra-small superparamagnetic iron oxide (CMEADM-U) accumulation in arteriosclerotic lesions using hyperlipidemic rabbits. MATERIAL AND METHODS: CMEADM-U at 0.5 mmol Fe/kg was administered to Watanabe hereditary atherosclerotic (WHHL) rabbits (n = 6, 24 sections) and New Zealand white (NZW) rabbits (n = 2, 6 sections). After 72 h, DECT was performed to prepare virtual monochromatic images (35 keV, 70 keV) and an iron-based map. Subsequently, the aorta was collected along with hematoxylin and eosin staining, Berlin blue (BB) staining, and RAM11 immunostaining. RESULTS: In the WHHL rabbits, CMEADM-U accumulation was not observed at 70 keV. However, CMEADM-U accumulation consistent with an arteriosclerotic lesion was observed at 35 keV and the iron-based map. On the other hand, in the NZW rabbits, there was no accumulation of CMEADM-U in any images. Further, there were significant differences in the iron-based map value at the site of accumulation among the grades of expression on BB staining and RAM11 immunostaining. In addition, there was a good correlation at 35 kev and iron-based map value (r = 0.42; P < 0.05). CONCLUSION: DECT imaging for CMEADM-U facilitated the assessment of macrophage accumulation in atherosclerotic lesions in an in vivo study using a rabbit model of induced aortic atherosclerosis.

Energy loss is related to CT fractional flow reserve progression in type 2 diabetes mellitus patients.

Background: We aimed to investigate the diagnostic value of energy loss (EL) and baseline CT fractional flow reserve (CT-FFR) computed using computational fluid dynamics to predict functional progression of coronary stenosis in patients with type 2 diabetes mellitus. Methods: This single-center prospective study included 61 patients with type 2 diabetes mellitus (mean age, 61 years ±9 [SD]; 43 men) showing 20-70 % stenosis who underwent serial coronary CT performed at 2-year interval between October 2015 and March 2020. A mesh-free simulation was performed to calculate the CT-FFR and EL. Functional progression was defined as ≥ 0.05 decrease in CT-FFR on the second coronary CT. Models using baseline CT-FFR and EL were compared by analyzing the receiver operating characteristic (ROC) curve. Results: Of the 94 vessels evaluated, 25 vessels (27 %) showed functional progression. EL at distal stenosis (ELdis) of vessels with functional progression was higher than that of vessels without functional progression (27.6 W/m3 [interquartile range (IQR): 15.0, 53.0] vs. 5.7 W/m3 [IQR: 2.3, 10.1], p < 0.001). Multivariable analysis showed that ELdis (per unit Ln(EL); odds ratio, 11.8; 95 % CI: 4.0-34.9; p < 0.001) remained as a predictor of functional progression after adjustment for diameter stenosis and baseline CT-FFR. The area under the ROC curve using ELdis (0.89; 95 % CI: 0.82-0.96) was higher than that using baseline CT-FFR (0.71; 95 % CI: 0.59-0.83; p < 0.001). Conclusion: When ELdis and baseline CT-FFR were considered, ELdis was a better predictor of functional progression of coronary stenosis.

Coronary flow disturbance assessed by vorticity as a cause of functionally significant stenosis.

OBJECTIVES: Vorticity calculated using computational fluid dynamics (CFD) could assess the flow disturbance generated by coronary stenosis. The purpose of this study was to investigate whether vorticity would be an underlying cause of functionally significant stenosis assessed by invasive fractional flow reserve (FFR). METHODS: This retrospective study included 113 patients who underwent coronary CT angiography showing intermediate stenosis and subsequent invasive FFR between December 2015 and March 2020. Vorticity at the stenosis site was calculated using a mesh-free CFD method. We also evaluated the minimum lumen area (MLA) and diameter stenosis (DS) of the lesion. Invasive FFR of ≤ 0.80 was considered functionally significant. Data were compared using Student's t-test and logistic regression analysis was performed. RESULTS: Of the evaluated 144 vessels, 53 vessels (37%) showed FFR ≤ 0.80. Vorticity of significant stenosis was significantly higher than non-significant stenosis (569 ± 78 vs. 328 ± 34 s-1, p < 0.001). A significant negative relationship was present between vorticity and invasive FFR (R2 = 0.31, p < 0.001). Multivariate logistic regression analysis including MLA and DS showed that vorticity (per 100 s-1, odds ratio: 1.36, 95% confidence interval: 1.21-1.57, p < 0.001) was a statistically significant factor to detect functional significance. The area under the receiver operating characteristic curve statistically significantly increased when vorticity was combined with DS and MLA (0.76 vs. 0.87, p = 0.001). CONCLUSIONS: Vorticity had a statistically significant negative relationship with invasive FFR independent of geometric stenosis. KEY POINTS: • Flow disturbance caused by coronary stenosis could be evaluated by calculating vorticity which is defined as the norm of the rotation of the velocity vector. • Vorticity was statistically significantly higher in stenosis with functional significance than stenosis without. • Vorticity has an additive value to detect functionally significant stenosis over geometrical stenosis.

Use of a deep-learning-based lumen extraction method to detect significant stenosis on coronary computed tomography angiography in patients with severe coronary calcification.

BACKGROUND: Coronary computed tomography angiography examinations are increasingly becoming established as a minimally invasive method for diagnosing coronary diseases. However, although various imaging and processing methods have been developed, coronary artery calcification remains a major limitation in the evaluation of the vascular lumen. Subtraction coronary computed tomography angiography (Sub-CCTA) is a method known to be able to reduce the influence of coronary artery calcification and is therefore feasible for improving the diagnosis of significant stenosis in patients with severe calcification. However, Sub-CCTA still involves some problems, such as the increased radiation dose due to plain (mask) imaging, extended breath-holding time, and misregistration due to differences in the imaging phase. Therefore, we considered using artificial intelligence instead of Sub-CCTA to visualize the coronary lumen with high calcification. Given this background, the present study aimed to evaluate the diagnostic performance of a deep learning-based lumen extraction method (DL-LEM) to detect significant stenosis on CCTA in 99 consecutive patients (891 segments) with severe coronary calcification from November 2015 to March 2018. We also estimated the impact of DL-LEM on the medical economics in Japan. RESULTS: The DL-LEM slightly improved the per-segment diagnostic accuracy from 74.5 to 76.4%, and the area under the curve (AUC) slightly improved from 0.752 to 0.767 (p = 0.030). When analyzing the 228 segments that could not be evaluated because of severe calcification on the original CCTA images, the DL-LEM improved the accuracy from 35.5 to 42.5%, and the AUC improved from 0.500 to 0.587 (p = 0.00018). As a result, DL-LEM analysis could have avoided invasive coronary angiography in 4/99 cases (per patient). From the calculated results, it was estimated that the number of exams that can be avoided in Japan in one year is approximately 747 for invasive coronary angiography, 219 for fractional flow reserve, and 248 for nuclear exam. The total amount of medical fee that could be reduced was 225,629,368 JPY. CONCLUSIONS: These findings suggest that the DL-LEM may improve the diagnostic performance in detecting significant stenosis in patients with severe coronary calcification. In addition, the results suggest that not a small medical economic effect can be expected.

Usefulness of Dapagliflozin for Nephrotic Syndrome Secondary to Diabetic Kidney Disease.

An 81-year-old woman with a medical history of type 2 diabetes mellitus and diabetic nephropathy was admitted with a diagnosis of multiple cerebellar infarctions. Proteinuria and leg edema were observed on the day after admission and diagnosed as nephrotic syndrome. Furosemide and spironolactone were started but showed no diuretic effect, and the renal function deteriorated. These agents were then replaced with dapagliflozin, which resulted in a positive diuretic effect and subsequent improvement of hypoalbuminemia and renal dysfunction. This case report demonstrates the utility of dapagliflozin for nephrotic syndrome to achieve a positive diuretic effect and improve hypoalbuminemia without deteriorating the renal function.

Prognostic value of the optimal measurement location of on-site CT-derived fractional flow reserve.

BACKGROUND: On-site computed tomography-derived fractional flow reserve (CT-FFR), using fluid structure interaction during multiple optimal diastolic phases, is of incremental diagnostic value. However, few studies have investigated prognosis, with the appropriate measurement location of CT-FFR, as a stand-alone modality. The aim of the present study was to assess the clinical impact on CT-FFR with an appropriate measurement. METHODS: A total of 370 consecutive patients (68 ±â€¯10 years, 75% male) who underwent coronary CT angiography (CCTA), showing 50-90% stenosis in at least one major epicardial vessel, were retrospectively analyzed and followed up for a median 2.9 years. CT-FFR values were measured at three points: 1 to 2 cm distal to the target lesion (CT-FFR1cm, 2cm) and the vessel terminus (CT-FFRlowest), and a CT-FFR value ≤0.80 was considered to be abnormal. The endpoint was major adverse cardiovascular events (MACE), a composite of cardiac death, non-fatal myocardial infarction, and unplanned revascularization. RESULTS: The incidence of MACE was 6.8% (25/370 patients). The Kaplan-Meier survival analysis in negative CT-FFR1/2cm revealed no significant difference in MACE between negative and positive CT-FFRlowest [p = 0.11/0.23 (1/2 cm vs lowest)]. Among 221 patients who did not undergo planned revascularization within 90 days of CCTA, no significant differences were noted in the incidence of MACE between negative and positive CT-FFRlowest (p = 0.11). In contrast, the risk of MACE was significantly higher with positive CT-FFR1/2cm [p = 0.0198/0.0002 (1/2 cm)]. CONCLUSIONS: In terms of the prognosis of patients with moderate to severe stenosis on CCTA, CT-FFR measured 1 to 2 cm distal to the target lesion may be feasible for the safe deferral of unnecessary invasive coronary angiography. Moreover, CT-FFR1/2cm showed better risk stratification than CT-FFRlowest based on future adverse cardiac events.

Identification of Risk Factors for Coronary Artery Disease in Asymptomatic Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Patients with diabetes mellitus (DM) are a high-risk group for coronary artery disease (CAD). In the present study, we investigated predictive factors to identify patients at high risk of CAD among asymptomatic patients with type 2 DM based on coronary computed tomographic angiography (CCTA) findings. METHODS: A single-center prospective study was performed on 452 consecutive patients with type 2 DM who were provided with a weekly hospital-based diabetes education program between 3 October 2015, and 31 March 2020. A total of 161 consecutive asymptomatic patients (male/female: 111/50, age: 57.3 ± 9.3 years) with type 2 DM without any known CAD underwent CCTA. Based on conventional coronary risk factors and non-invasive examination, i.e., measurement of intima-media thickness, subcutaneous and visceral fat area, a stress electrocardiogram test, and the Agatston score, patients with obstructive CAD, CT-verified high-risk plaques (CT-HRP), and optimal revascularization within 90 days were evaluated. RESULTS: Current smoking (OR, 4.069; 95% C.I., 1.578-10.493, p = 0.0037) and the Agatston score ≥100 (OR, 18.034; 95% C.I., 6.337-51.324, p = 0.0001) were independent predictive factors for obstructive CAD, while current smoking (OR, 5.013; 95% C.I., 1.683-14.931, p = 0.0038) was an independent predictive factor for CT-HRP. Furthermore, insulin treatment (OR, 5.677; 95% C.I., 1.223-26.349, p = 0.0266) was the only predictive factor that correlated with optimal revascularization within 90 days. CONCLUSIONS: In asymptomatic patients with type 2 DM, current smoking, an Agatston score ≥100, and insulin treatment were independent predictive factors of patients being at high-risk for CAD. However, non-invasive examinations except for Agatston score were not independent predictors of patients being at high risk of CAD.

Clinical significance of 123I-BMIPP washout rate in patients with uncertain chronic heart failure.

BACKGROUND: Recently, triglyceride deposit cardiomyovasculopathy (TGCV) with defective intracellular lipolysis was found to be a disease that causes heart failure. As a diagnostic criterion for TGCV, an Iodaine-123-ß-methyl iodophenyl-pentadecanoic acid washout rate (BMIPP WOR) of < 10% is used, but its clinical significance in patients with heart failure remains to be clarified. METHODS: In 62 hospitalized patients with chronic heart failure, 123I-BMIPP myocardial single-photon emission computed tomography (SPECT) was performed predischarge state. The prevalence of TGCV was investigated. Subsequently, follow-up was conducted for ≥ 90 days (mean: 724.6 ± 392.7 days), and the association between the BMIPP WOR and cardiac events was examined, establishing all-cause mortality and admission due to heart failure as endpoints. RESULTS: Of the 62 patients, the WOR was < 10% in 41 (66.1%). Of these, 26 (41.9%) were diagnosed with definite TGCV. Furthermore, cardiac events were noted in 12 patients (19.4%). Analysis with Cox proportional hazards models showed that the BMIPP WOR < 4.5% was a significant event-predicting factor [HR 4.29, 95% CI: 1.20-16.87; p = 0.0245]. On a Kaplan-Meier curve, the WOR was 4.5%; there was a significant difference in the incidence of events (p = 0.0298). CONCLUSION: In the predischarge state of heart failure, 123I-BMIPP myocardial SPECT was performed. In approximately 40% of the patients, a diagnosis of TGCV was made. The results suggested that the BMIPP WOR is useful for predicting the prognosis of chronic heart failure patients regardless of TGCV.

Effect of a novel nasal oxytocin spray with enhanced bioavailability on autism: a randomized trial.

Although intranasal oxytocin is expected to be a novel therapy for the core symptoms of autism spectrum disorder, which has currently no approved medication, the efficacy of repeated administrations was inconsistent, suggesting that the optimal dose for a single administration of oxytocin is not optimal for repeated administration. The current double-blind, placebo-controlled, multicentre, crossover trial (ClinicalTrials.gov Identifier: NCT03466671) was aimed to test the effect of TTA-121, a new formulation of intranasal oxytocin spray with an enhanced bioavailability (3.6 times higher than Syntocinon® spray, as assessed by area under the concentration-time curve in rabbit brains), which enabled us to test a wide range of multiple doses, on autism spectrum disorder core symptoms and to determine the dose-response relationship. Four-week administrations of TTA-121, at low dose once per day (3 U/day), low dose twice per day (6 U/day), high dose once per day (10 U/day), or high dose twice per day (20 U/day), and 4-week placebo were administered in a crossover manner. The primary outcome was the mean difference in the reciprocity score (range: 0-14, higher values represent worse outcomes) on the Autism Diagnostic Observation Schedule between the baseline and end point of each administration period. This trial with two administration periods and eight groups was conducted at seven university hospitals in Japan, enrolling adult males with high-functioning autism spectrum disorder. Enrolment began from June 2018 and ended December 2019. Follow-up ended March 2020. Of 109 males with high-functioning autism spectrum disorder who were randomized, 103 completed the trial. The smallest P-value, judged as the dose-response relationship, was the contrast with the peak at TTA-121 6 U/day, with inverted U-shape for both the full analysis set (P = 0.182) and per protocol set (P = 0.073). The Autism Diagnostic Observation Schedule reciprocity score, the primary outcome, was reduced in the TTA-121 6 U/day administration period compared with the placebo (full analysis set: P = 0.118, mean difference = -0.5; 95% CI: -1.1 to 0.1; per protocol set: P = 0.012, mean difference = -0.8; 95% CI: -1.3 to -0.2). The per protocol set was the analysis target population, consisting of all full analysis set participants except those who deviated from the protocol. Most dropouts from the full analysis set to the per protocol set occurred because of poor adherence to the test drug (9 of 12 in the first period and 8 of 15 in the second period). None of the secondary clinical and behavioural outcomes were significantly improved with the TTA-121 compared with the placebo in the full analysis set. A novel intranasal spray of oxytocin with enhanced bioavailability enabled us to test a wide range of multiple doses, revealing an inverted U-shape dose-response curve, with the peak at a dose that was lower than expected from previous studies. The efficacy of TTA-121 shown in the current exploratory study should be verified in a future large-scale, parallel-group trial.

Feasibility of CT Angiography-derived Kinetic Energy of Coronary Flow to Improve the Detection of Hemodynamically Significant Coronary Stenosis.

Purpose: To investigate whether coronary flow kinetic energy has incremental value over simulated fractional flow reserve (sFFR) in diagnosing hemodynamically significant stenosis assessed with coronary CT angiography and invasive fractional flow reserve (FFR). Materials and Methods: This single-center retrospective study included 113 patients (mean age, 68 years ± 9 [SD]; 80 men) who underwent coronary CT angiography showing intermediate stenosis (30%-70% stenosis) and subsequent invasive FFR between December 2015 and March 2020. Kinetic energy was calculated using proximal coronary diameter and myocardial mass of the stenotic region. A mesh-free simulation was performed to calculate the sFFR. Invasive FFR of 0.80 or less indicated hemodynamically significant stenosis. Models using diameter stenosis, kinetic energy, and sFFR were compared by analyzing the receiver operating characteristic curve. Results: Of the 144 vessels evaluated, 53 vessels (37%) had hemodynamically significant stenosis. Kinetic energy of vessels with significant stenosis was higher than that of vessels with nonsignificant stenosis (79 mJ/kg [IQR, 58-104 mJ/kg] vs 36 mJ/kg [IQR, 23-59 mJ/kg]; P < .001). Multivariable analysis including diameter stenosis and sFFR showed that kinetic energy (per 20 mJ/kg; odds ratio, 1.92; 95% CI: 1.37, 2.95; P < .001) was a predictor of hemodynamically significant stenosis. Adding kinetic energy to diameter stenosis and sFFR improved the area under the receiver operating characteristic curve from 0.89 (95% CI: 0.84, 0.95) to 0.93 (95% CI: 0.89, 0.97) (P = .04). Conclusion: Kinetic energy had incremental value over sFFR in detecting hemodynamically significant stenosis assessed with invasive FFR.Keywords: Coronary CT Angiography, Coronary Arteries, Fractional Flow Reserve, Kinetic Energy, Cardiac Supplemental material is available for this article © RSNA, 2022.

Digital Breast Tomosynthesis Complements Two-Dimensional Synthetic Mammography for Secondary Examination of Breast Cancer.

OBJECTIVE: To compare the performance of two-dimensional synthetic mammography (SM) combined with digital breast tomosynthesis (DBT) (SM/DBT) and full-field digital mammography (FFDM) including women with DBT (FFDM/DBT) undergoing secondary examination for breast cancer. MATERIAL AND METHODS: Out of 186 breasts, including 52 with breast cancers; FFDM/DBT and SM/DBT findings were interpreted by four expert clinicians. Radiation doses of FFDM, SM/DBT, and FFDM/DBT were determined. Inter-rater reliabilities were analyzed between readers and between FFDM/DBT and SM/DBT by Cohen's Kappa coefficients. Diagnostic accuracy was compared between SM/DBT and FFDM/DBT by Fisher's exact tests. Two representative cancer cases were examined for differences in the interpretation between FFDM and SM. RESULTS: A higher radiation dose was required in FFDM/DBT than in SM/DBT (median: 1.50 mGy vs. 2.95 mGy). Inter-rater reliabilities were similar between both readers and modalities. Both sensitivity and specificity were equivalent in FFDM/DBT and SM/DBT (p = 0.874-1.00). Compared with FFDM, SM did not clearly show abnormalities with subtle margins in the two representative cancer cases. CONCLUSION: SM/DBT had a similar performance to FFDM/DBT in detecting breast abnormalities but requires less radiation. DBT complements SM to improve accuracy to a level equivalent to that of FFDM. Taken together, SM/DBT may be a good substitute for FFDM/DBT for the secondary examination of breast cancer.