Practice recommendation for measuring washout rates in 123I-BMIPP fatty acid images.

The purpose of this practice recommendation is to specifically identify the critical steps involved in performing and interpreting 123I-ß-methyl-iodophenyl-pentadecanoic acid (BMIPP) single-photon emission computed tomography (SPECT) and measurement of washout rate (WR) from the heart. This document will cover backgrounds, patient preparation, testing procedure, visual image interpretation, quantitation methods using planar and SPECT studies, and reporting of WR. The pitfall and some tips for the calculation of 123I-BMIPP WR are also included. The targets of global and regional WR calculation include ischemic heart disease, cardiomyopathy, heart failure, and triglyceride deposit cardiomyovasculopathy, an emerging rare heart disease.

Practice Recommendation for Measuring Washout Rates in 123I-BMIPP Fatty Acid Images.

The purpose of this practice recommendation is to specifically identify the critical steps involved in performing and interpreting 123I-ß-methyl-iodophenyl-pentadecanoic acid (BMIPP) single-photon emission computed tomography (SPECT) and measurement of washout rate (WR) from the heart. This document will cover backgrounds, patient preparation, testing procedure, visual image interpretation, quantitation methods using planar and SPECT studies, and reporting of WR. The pitfall and some tips for the calculation of 123I-BMIPP WR are also included. The targets of global and regional WR calculation include ischemic heart disease, cardiomyopathy, heart failure, and triglyceride deposit cardiomyovasculopathy, an emerging rare heart disease.

Determination of lipid-rich plaques by artificial intelligence-enabled quantitative computed tomography using near-infrared spectroscopy as reference.

BACKGROUND AND AIMS: Artificial intelligence quantitative CT (AI-QCT) determines coronary plaque morphology with high efficiency and accuracy. Yet, its performance to quantify lipid-rich plaque remains unclear. This study investigated the performance of AI-QCT for the detection of low-density noncalcified plaque (LD-NCP) using near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS). METHODS: The INVICTUS Registry is a multi-center registry enrolling patients undergoing clinically indicated coronary CT angiography and IVUS, NIRS-IVUS, or optical coherence tomography. We assessed the performance of various Hounsfield unit (HU) and volume thresholds of LD-NCP using maxLCBI4mm ≥ 400 as the reference standard and the correlation of the vessel area, lumen area, plaque burden, and lesion length between AI-QCT and IVUS. RESULTS: This study included 133 atherosclerotic plaques from 47 patients who underwent coronary CT angiography and NIRS-IVUS The area under the curve of LD-NCP<30HU was 0.97 (95% confidence interval [CI]: 0.93-1.00] with an optimal volume threshold of 2.30 mm3. Accuracy, sensitivity, and specificity were 94% (95% CI: 88-96%], 93% (95% CI: 76-98%), and 94% (95% CI: 88-98%), respectively, using <30 HU and 2.3 mm3, versus 42%, 100%, and 27% using <30 HU and >0 mm3 volume of LD-NCP (p < 0.001 for accuracy and specificity). AI-QCT strongly correlated with IVUS measurements; vessel area (r2 = 0.87), lumen area (r2 = 0.87), plaque burden (r2 = 0.78) and lesion length (r2 = 0.88), respectively. CONCLUSIONS: AI-QCT demonstrated excellent diagnostic performance in detecting significant LD-NCP using maxLCBI4mm ≥ 400 as the reference standard. Additionally, vessel area, lumen area, plaque burden, and lesion length derived from AI-QCT strongly correlated with respective IVUS measurements.

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.

Clinical impacts of CT-derived fractional flow reserve under insurance reimbursement: Results from multicenter, prospective registry.

BACKGROUND: Although computed tomography-derived fractional flow reserve (FFRCT) has been reimbursed in a few countries, its impacts on daily practice of coronary artery diseases are not fully elucidated. We evaluated the clinical impacts of FFRCT under the real Japanese insurance reimbursement. METHODS: In the multicenter prospective registry: DYNAMIC-FFRCT study, a total of 410 patients who underwent FFRCT analysis under reimbursement were prospectively enrolled at 6 Japanese sites from October 2019 to November 2021. Coronary CT angiography and FFRCT findings, treatment plans, and 90-day outcomes were recorded. The primary endpoint was the redirection rate from the tests that might be expected without FFRCT [invasive coronary angiography (ICA)-selected group, myocardial perfusion single photon emission CT (MPS)-selected group, optimal medical therapy (OMT)-selected group, and others-selected group] to those that were actually performed based on FFRCT. RESULTS: ICA could be avoided in 39.5 % in the ICA-selected group (N = 233). In particular, in 94.3 % of patients with an FFRCT value of >0.80, additional examinations, such as ICA, were avoided. In addition, in the MPS-selected group (N = 133), 92.6 % had no additional tests with FFRCT > 0.80, while only 2 cases with FFRCT ≤ 0.80 underwent additional MPS examination. On the contrary, 33.3 % of the OMT-selected group (N = 33) had FFRCT ≤ 0.80. Approximately, 35 % medical cost reduction was also finally expected. CONCLUSION: Introduction of FFRCT could not only reduce unnecessary ICA and be a test that replaces the conventional non-invasive functional assessment modality but also result in medical cost reduction even when used under real Japanese insurance reimbursement.

Rationale and design of the INVICTUS Registry: (Multicenter Registry of Invasive and Non-Invasive imaging modalities to compare Coronary Computed Tomography Angiography, Intravascular Ultrasound and Optical Coherence Tomography for the determination of Severity, Volume and Type of coronary atherosclerosiS).

BACKGROUND: Coronary CT angiography (CCTA) is a first-line noninvasive imaging modality for evaluating coronary artery disease (CAD). Recent advances in CCTA technology enabled semi-automated detection of coronary arteries and atherosclerosis. However, there have been to date no large-scale validation studies of automated assessment of coronary atherosclerosis phenotype and coronary artery dimensions by artificial intelligence (AI) compared to current standard invasive imaging. METHODS: INVICTUS registry is a multicenter, retrospective, and prospective study designed to evaluate the dimensions of coronary arteries, as well as the characteristic, volume, and phenotype of coronary atherosclerosis by CCTA, compared with the invasive imaging modalities including intravascular ultrasound (IVUS), near-infrared spectroscopy (NIRS)-IVUS and optical coherence tomography (OCT). All patients clinically underwent both CCTA and invasive imaging modalities within three months. RESULTS: Patients data are sent to the core-laboratories to analyze for stenosis severity, plaque characteristics and volume. The variables for CCTA are measured using an AI-based automated software and assessed independently with the variables measured at the imaging core laboratories for IVUS, NIRS-IVUS, and OCT in a blind fashion. CONCLUSION: The INVICTUS registry will provide new insights into the diagnostic value of CCTA for determining coronary atherosclerosis phenotype and coronary artery dimensions compared to IVUS, NIRS-IVUS, and OCT. Our findings will potentially shed new light on precision medicine informed by an AI-based coronary CTA assessment of coronary atherosclerosis burden, composition, and severity. (ClinicalTrials.gov: NCT04066062).

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.

Feasibility of Simple Evaluation of Coronary Artery Calcium Using a Number of Chest Computed Tomography Slices: A Multicenter Study.

Objective: We aimed to evaluate the visual measurements of coronary artery calcium (CAC) on nonelectrocardiogram (ECG)-gated chest computed tomography (CT) using a simple scoring method that involves counting the number of CT slices containing CAC. Materials and Methods: We analyzed 163 participants who underwent both coronary and chest CT examinations at six centers within 3 months. Agatston scores were calculated on standard ECG-gated scans and classified as none (0), mild (1-99), moderate (100-400), or severe (>400). Next, chest CT images were reconstructed to standard 5.0 mm axial slices. Then, CAC on chest CT scans was measured using two methods: the Weston score (sum of the assigned score of each vessel, range: 0-12) and number of slices showing CAC (Ca-slice#). Results: When the Weston score and Ca-slice# were divided into four levels according to the optimal divisional levels corresponding to the Agatston score classes, good agreements with the 4-grade Agatston score were observed (kappa value=0.610 and 0.794, respectively). The sensitivity and specificity of Ca-slice# ≥9 to identify severe Agatston scores of >400 were 86% and 96%, respectively. Conclusion: The Ca-slice#, a simple scoring method using chest CT scans, was in good agreement with the ECG-gated Agatston score.

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.

Impact of a Deep Learning-based Super-resolution Image Reconstruction Technique on High-contrast Computed Tomography: A Phantom Study.

RATIONALE AND OBJECTIVES: Deep-learning-based super-resolution image reconstruction (DLSRR) is a novel image reconstruction technique that is expected to contribute to improvement in spatial resolution as well as noise reduction through learning from high-resolution computed tomography (CT). This study aims to evaluate image quality obtained with DLSRR and assess its clinical potential. MATERIALS AND METHODS: CT images of a Mercury CT 4.0 phantom were obtained using a 320-row multi-detector scanner at tube currents of 100, 200, and 300 mA. Image data were reconstructed by filtered back projection (FBP), hybrid iterative reconstruction (HIR), model-based iterative reconstruction (MBIR), deep-learning-based image reconstruction (DLR), and DLSRR at image reconstruction strength levels of mild, standard, and strong. Noise power spectrum (NPS), task transfer function (TTF), and detectability index were calculated. RESULTS: The magnitude of the noise-reducing effect in comparison with FBP was in the order MBIR

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.

123I-BMIPP Scintigraphy Shows That CNT-01 (Tricaprin) Improves Myocardial Lipolysis in Patients with Idiopathic Triglyceride Deposit Cardiomyovasculopathy: First Randomized Controlled, Exploratory Trial for TGCV.

Background: Triglyceride deposit cardiomyovasculopathy (TGCV) is a rare intractable cardiovascular disorder (Orphanet ORPHAcode: 565612) in which defective intracellular lipolysis results in heart failure and coronary artery disease. Myocardial scintigraphy with 123I-ß-methyl-p-iodophenylpentadecanoic acid (BMIPP) is useful to evaluate myocardial TG metabolism; its washout rate (WR) reflects myocardial lipolysis. This study reports the effects of CNT-01 (tricaprin), a developing orphan drug to facilitate lipolysis, on BMIPP-WR in patients with TGCV. Methods: An investigator-initiated, multicenter, randomized, double-blind exploratory, trial (Phase IIa) was conducted (UMIN000035403). Seventeen patients with idiopathic TGCV were orally administered 1.5 g/day of CNT-01 or placebo for 8 weeks. Endpoints included delta BMIPP-WR and clinical parameters such as 6-minwalk distance and TGCV severity score. Results: During the protocol, delta BMIPP-WRs were -0.26±3.28 and 7.08±3.28% (95% confidence intervals, -7.36 to 6.84 and -0.01 to 14.18) in the placebo and CNT-01 groups, respectively. The baseline-adjusted difference of delta BMIPP-WR between the two groups was significant (p=0.035) after one patient was excluded from the placebo group because of pseudonormalization of BMIPP-WR related to coronary bypass graft stenosis. Clinical parameters did not show significant changes. Conclusions: This study proved the mechanism of CNT-01 to improve myocardial lipolysis in TGCV, as demonstrated by BMIPP scintigraphy.

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.

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.