Variation of computed tomography-derived extracellular volume fraction and the impact of protocol parameters: A systematic review and meta-analysis.

BACKGROUND: Cardiac computed tomography quantification of extracellular volume fraction (CT-ECV) is an emerging biomarker of myocardial fibrosis which has demonstrated high reproducibility, diagnostic and prognostic utility. However, there has been wide variation in the CT-ECV protocol in the literature and useful disease cut-offs are yet to be established. The objectives of this meta-analysis were to describe mean CT-ECV estimates and to estimate the effect of CT-ECV protocol parameters on between-study variation. METHODS: We conducted a meta-analysis of studies assessing CT-ECV in healthy and diseased participants. We used meta-analytic methods to pool estimates of CT-ECV and performed meta-regression to identify the contribution of protocol parameters to CT-ECV heterogeneity. RESULTS: Thirteen studies had a total of 248 healthy participants who underwent CT-ECV assessment. Studies of healthy participants had high variation in CT-ECV protocol parameters. The pooled estimate of CT-ECV in healthy participants was 27.6% (95%CI 25.7%-29.4%) with significant heterogeneity (I2 â€‹= â€‹93%) compared to 50.2% (95%CI 46.2%-54.2%) in amyloidosis, 31.2% (28.5%-33.8%) in severe aortic stenosis and 36.9% (31.6%-42.3%) in non-ischaemic dilated cardiomyopathies. Meta-regression revealed that CT protocol parameters account for approximately 25% of the heterogeneity in CT-ECV estimates. CONCLUSION: CT-ECV estimates for healthy individuals vary widely in the literature and there is significant overlap with estimates in cardiac disease. One quarter of this heterogeneity is explained by differences in CT-ECV protocol parameters. Standardization of CT-ECV protocols is necessary for widespread implementation of CT-ECV assessment for diagnosis and prognosis.

Curcumin Disrupts a Positive Feedback Loop between ADMSCs and Cancer Cells in the Breast Tumor Microenvironment via the CXCL12/CXCR4 Axis.

Adipose tissue has a significant impact on breast cancer initiation and progression owing to its substantial proportion in the breast. Adipose-derived mesenchymal stem cells (ADMSCs) are major players in the breast tumor microenvironment (TME) as they interact with cancer cells. The intricate interaction between ADMSCs and cancer cells not only drives the differentiation of ADMSCs into cancer-associated fibroblasts (CAFs) but also the metastasis of cancer cells, which is attributed to the CXCL12/CXCR4 axis. We investigated the effects of curcumin, a flavonoid known for CXCL12/CXCR4 axis inhibition, on breast TME by analyzing whether it can disrupt the ADMSC-cancer positive loop. Using MCF7 breast cancer cell-derived conditioned medium (MCF7-CM), we induced ADMSC transformation and verified that curcumin diminished the phenotypic change, inhibiting CAF marker expression. Additionally, curcumin suppressed the CXCL12/CXCR4 axis and its downstream signaling both in ADMSCs and MCF7 cells. The CM from ADMSCs, whose ADMSC-to-CAF transformation was repressed by the curcumin treatment, inhibited the positive feedback loop between ADMSCs and MCF7 as well as epithelial-mesenchymal transition in MCF7. Our study showed that curcumin is a potent anti-cancer agent that can remodel the breast TME, thereby restricting the ADMSC-cancer positive feedback loop associated with the CXCL12/CXCR4 axis.

Regulation of base excision repair during adipogenesis and osteogenesis of bone marrow-derived mesenchymal stem cells.

Bone marrow-derived human mesenchymal stem cells (hMSCs) can differentiate into various lineages, such as chondrocytes, adipocytes, osteoblasts, and neuronal lineages. It has been shown that the high-efficiency DNA-repair capacity of hMSCs is decreased during their differentiation. However, the underlying its mechanism during adipogenesis and osteogenesis is unknown. Herein, we investigated how alkyl-damage repair is modulated during adipogenic and osteogenic differentiation, especially focusing on the base excision repair (BER) pathway. Response to an alkylation agent was assessed via quantification of the double-strand break (DSB) foci and activities of BER-related enzymes during differentiation in hMSCs. Adipocytes showed high resistance against methyl methanesulfonate (MMS)-induced alkyl damage, whereas osteoblasts were more sensitive than hMSCs. During the differentiation, activities, and protein levels of uracil-DNA glycosylase were found to be regulated. In addition, ligation-related proteins, such as X-ray repair cross-complementing protein 1 (XRCC1) and DNA polymerase ß, were upregulated in adipocytes, whereas their levels and recruitment declined during osteogenesis. These modulations of BER enzyme activity during differentiation influenced DNA repair efficiency and the accumulation of DSBs as repair intermediates in the nucleus. Taken together, we suggest that BER enzymatic activity is regulated in adipogenic and osteogenic differentiation and these alterations in the BER pathway led to different responses to alkyl damage from those in hMSCs.

Diagnostic accuracy of bone scintigraphy imaging for transthyretin cardiac amyloidosis: systematic review and meta-analysis.

BACKGROUND: Bone scintigraphy imaging is frequently used to investigate patients with suspected transthyretin cardiac amyloidosis (ATTR-CM). However, the reported accuracy for interpretation approaches has changed over time. We performed a systematic review and meta-analysis to determine the diagnostic accuracy of visual planar grading, heart-to-contralateral (HCL) ratio, and quantitative analysis of SPECT imaging and evaluate reasons for shifts in reported accuracy. METHODS: We performed a systematic review to identify studies of the diagnostic accuracy of bone scintigraphy for ATTR-CM from 1990 until February 2023 using PUBMED and EMBASE. Studies were reviewed separately by two authors for inclusion and for risk of bias assessment. Summary receiver operating characteristic curves and operating points were determined with hierarchical modeling. RESULTS: Out of a total of 428 identified studies, 119 were reviewed in detail and 23 were included in the final analysis. The studies included a total of 3954 patients, with ATTR-CM diagnosed in 1337 (39.6%) patients and prevalence ranging from 21 to 73%. Visual planar grading and quantitative analysis had higher diagnostic accuracy (.99) than HCL ratio (.96). Quantitative analysis of SPECT imaging had the highest specificity (97%) followed by planar visual grade (96%) and HCL ratio (93%). ATTR-CM prevalence accounted for some of the observed between study heterogeneity. CONCLUSIONS: Bone scintigraphy imaging is highly accurate for identifying patients with ATTR-CM, with between study heterogeneity in part explained by differences in disease prevalence. We identified small differences in specificity, which may have important clinical implications when applied to low-risk screening populations.

Chronic Exposure to TDI Induces Cell Migration and Invasion via TGF-ß1 Signal Transduction.

Toluene diisocyanate (TDI) is commonly used in manufacturing, and it is highly reactive and causes respiratory damage. This study aims to identify the mechanism of tumorigenesis in bronchial epithelial cells induced by chronic TDI exposure. In addition, transcriptome analysis results confirmed that TDI increases transforming growth factor-beta 1 (TGF-ß1) expression and regulates genes associated with cancerous characteristics in bronchial cells. Our chronically TDI-exposed model exhibited elongated spindle-like morphology, a mesenchymal characteristic. Epithelial-mesenchymal transition (EMT) was evaluated following chronic TDI exposure, and EMT biomarkers increased concentration-dependently. Furthermore, our results indicated diminished cell adhesion molecules and intensified cell migration and invasion. In order to investigate the cellular regulatory mechanisms resulting from chronic TDI exposure, we focused on TGF-ß1, a key factor regulated by TDI exposure. As predicted, TGF-ß1 was significantly up-regulated and secreted in chronically TDI-exposed cells. In addition, SMAD2/3 was also activated considerably as it is the direct target of TGF-ß1 and TGF-ß1 receptors. Inhibiting TGF-ß1 signaling through blocking of the TGF-ß receptor attenuated EMT and cell migration in chronically TDI-exposed cells. Our results corroborate that chronic TDI exposure upregulates TGF-ß1 secretion, activates TGF-ß1 signal transduction, and leads to EMT and other cancer properties.

Relationship between impaired myocardial blood flow by positron emission tomography and low-attenuation plaque burden and pericoronary adipose tissue attenuation from coronary computed tomography: From the prospective PACIFIC trial.

BACKGROUND: Positron emission tomography (PET) is the clinical gold standard for quantifying myocardial blood flow (MBF). Pericoronary adipose tissue (PCAT) attenuation may detect vascular inflammation indirectly. We examined the relationship between MBF by PET and plaque burden and PCAT on coronary CT angiography (CCTA). METHODS: This post hoc analysis of the PACIFIC trial included 208 patients with suspected coronary artery disease (CAD) who underwent [15O]H2O PET and CCTA. Low-attenuation plaque (LAP, < 30HU), non-calcified plaque (NCP), and PCAT attenuation were measured by CCTA. RESULTS: In 582 vessels, 211 (36.3%) had impaired per-vessel hyperemic MBF (≤ 2.30 mL/min/g). In multivariable analysis, LAP burden was independently and consistently associated with impaired hyperemic MBF (P = 0.016); over NCP burden (P = 0.997). Addition of LAP burden improved predictive performance for impaired hyperemic MBF from a model with CAD severity and calcified plaque burden (P < 0.001). There was no correlation between PCAT attenuation and hyperemic MBF (r = - 0.11), and PCAT attenuation was not associated with impaired hyperemic MBF in univariable or multivariable analysis of all vessels (P > 0.1). CONCLUSION: In patients with stable CAD, LAP burden was independently associated with impaired hyperemic MBF and a stronger predictor of impaired hyperemic MBF than NCP burden. There was no association between PCAT attenuation and hyperemic MBF.

De Novo Design of AC-P19M, a Novel Anticancer Peptide with Apoptotic Effects on Lung Cancer Cells and Anti-Angiogenic Activity.

Despite the current developments in cancer therapeutics, efforts to excavate new anticancer agents continue rigorously due to obstacles, such as side effects and drug resistance. Anticancer peptides (ACPs) can be utilized to treat cancer because of their effectiveness on a variety of molecular targets, along with high selectivity and specificity for cancer cells. In the present study, a novel ACP was de novo designed using in silico methods, and its functionality and molecular mechanisms of action were explored. AC-P19M was discovered through functional prediction and sequence modification based on peptide sequences currently available in the database. The peptide exhibited anticancer activity against lung cancer cells, A549 and H460, by disrupting cellular membranes and inducing apoptosis while showing low toxicity towards normal and red blood cells. In addition, the peptide inhibited the migration and invasion of lung cancer cells and reversed epithelial-mesenchymal transition. Moreover, AC-P19M showed anti-angiogenic activity through the inhibition of vascular endothelial growth factor receptor 2 signaling. Our findings suggest that AC-P19M is a novel ACP that directly or indirectly targets cancer cells, demonstrating the potential development of an anticancer agent and providing insights into the discovery of functional substances based on an in silico approach.

Quercetin and Isorhamnetin Reduce Benzo[a]pyrene-Induced Genotoxicity by Inducing RAD51 Expression through Downregulation of miR-34a.

Benzo[a]pyrene (B[a]P) is metabolized in the liver into highly reactive mutagenic and genotoxic metabolites, which induce carcinogenesis. The mutagenic factors, including B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE) and reactive oxygen species, generated during B[a]P metabolism can cause DNA damage, such as BPDE-DNA adducts, 8-oxo-dG, and double-strand breaks (DSBs). In this study, we mechanistically investigated the effects of quercetin and its major metabolite isorhamnetin on the repair of B[a]P-induced DNA DSBs. Whole-transcriptome analysis showed that quercetin and isorhamnetin each modulate the expression levels of genes involved in DNA repair, especially those in homologous recombination. RAD51 was identified as a key gene whose expression level was decreased in B[a]P-treated cells and increased by quercetin or isorhamnetin treatment. Furthermore, the number of γH2AX foci induced by B[a]P was significantly decreased by quercetin or isorhamnetin, whereas RAD51 mRNA and protein levels were increased. Additionally, among the five microRNAs (miRs) known to downregulate RAD51, miR-34a level was significantly downregulated by quercetin or isorhamnetin. The protective effect of quercetin or isorhamnetin was lower in cells transfected with a miR-34a mimic than in non-transfected cells, and the B[a]P-induced DNA DSBs remained unrepaired. Our results show that quercetin and isorhamnetin each upregulates RAD51 by downregulating miR-34a and thereby suppresses B[a]P-induced DNA damage.

Association between hypercholesterolemia and mortality risk among patients referred for cardiac imaging test: Evidence of a "cholesterol paradox?"

AIM: Some observational studies have observed a lower, rather than higher, mortality rate in association with hypercholesterolemia during follow-up of patients after cardiac stress testing. We aim to assess the relationship of hypercholesterolemia and other CAD risk factors to mortality across a wide spectrum of patients referred for various cardiac tests. METHODS AND RESULTS: We identified four cardiac cohorts: 64,357 patients undergoing coronary artery calcium (CAC) scanning, 10,814 patients undergoing coronary CT angiography (CCTA), 31,411 patients without known CAD undergoing stress/rest single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), and 5051 patients with known CAD undergoing stress/rest SPECT-MPI. Each cohort was followed for all-cause mortality using risk-adjusted Cox models. We pooled the hazard ratios between cohorts with a random effects model. Baseline risk varied markedly among cohorts, from an annualized mortality rate of 0.31%/year in CAC patients to 3.63%/year among SPECT-MPI patients with known CAD. Hypertension, diabetes, and smoking were each associated with increased mortality in each patient cohort (pooled hazard ratio[95% CI]: 1.38[1.33-1.44], 1.88[1.76-2.00], and 1.67[1.48-1.86], respectively). By contrast, hypercholesterolemia was associated with decreased rather than increased mortality (pooled hazard ratio[95% CI]: 0.71[0.58-0.84]). Analysis of serum lipids among 7744 patients undergoing CAC or CCTA scanning revealed an inverse relationship between LDL cholesterol and mortality. CONCLUSIONS: Among a broad spectrum of patients referred for a variety of cardiac tests and ranging from low to high clinical risk, hypercholesterolemia was not associated with increased mortality risk. Our findings suggest that hypercholesterolemia may be sensitive to confounding by other clinical factors and post-test treatment changes in patient populations.

Evaluating the Coronary Artery Disease Consortium Model and the Coronary Artery Calcium Score in Predicting Obstructive Coronary Artery Disease in a Symptomatic Mixed Asian Cohort.

Background The utility of a given pretest probability score in predicting obstructive coronary artery disease (CAD) is population dependent. Previous studies investigating the additive value of coronary artery calcium (CAC) on pretest probability scores were predominantly limited to Western populations. This retrospective study seeks to evaluate the CAD Consortium (CAD2) model in a mixed Asian cohort within Singapore with stable chest pain and to evaluate the incremental value of CAC in predicting obstructive CAD. Methods and Results Patients who underwent cardiac computed tomography and had chest pain were included. The CAD2 clinical model comprised of age, sex, symptom typicality, diabetes, hypertension, hyperlipidemia, and smoking status and was compared with the CAD2 extended model that added CAC to assess the incremental value of CAC scoring, as well as to the corresponding locally calibrated local assessment of the heart models. A total of 522 patients were analyzed (mean age 54±11 years, 43.1% female). The CAD2 clinical model obtained an area under the curve of 0.718 (95% CI, 0.668-0.767). The inclusion of CAC score improved the area under the curve to 0.896 (95% CI, 0.867-0.925) in the CAD2 models and from 0.767 (95% CI, 0.721-0.814) to 0.926 (95% CI, 0.900-0.951) in the local assessment of the heart models. The locally calibrated local assessment of the heart models showed better discriminative performance than the corresponding CAD2 models (P<0.05 for all). Conclusions The CAD2 model was validated in a symptomatic mixed Asian cohort and local calibration further improved performance. CAC scoring provided significant incremental value in predicting obstructive CAD.

Diagnostic Accuracy of Cardiovascular Magnetic Resonance for Cardiac Transplant Rejection: A Meta-Analysis.

OBJECTIVES: The aim of this meta-analysis was to assess the diagnostic performance of various CMR imaging parameters for evaluating acute cardiac transplant rejection. BACKGROUND: Endomyocardial biopsy is the current gold standard for detection of acute cardiac transplant rejection. Cardiac magnetic resonance (CMR) is uniquely capable of myocardial tissue characterization and may be useful as a noninvasive alternative for the diagnosis of graft rejection. METHODS: PubMed and Web of Science were searched for relevant publications reporting on the use of CMR myocardial tissue characterization for detection of acute cardiac transplant rejection with endomyocardial biopsy as the reference standard. Pooled sensitivity, specificity, and hierarchical modeling-based summary receiver-operating characteristic curves were calculated. RESULTS: Of 478 papers, 10 studies comprising 564 patients were included. The sensitivity and specificity for the detection of acute cardiac transplant rejection were 84.6 (95% CI: 65.6-94.0) and 70.1 (95% CI: 54.2-82.2) for T1, 86.5 (95% CI: 72.1-94.1) and 85.9 (95% CI: 65.2-94.6) for T2, 91.3 (95% CI: 63.9-98.4) and 67.6 (95% CI: 56.1-77.4) for extracellular volume fraction (ECV), and 50.1 (95% CI: 31.2-68.9) and 60.2 (95% CI: 36.7-79.7) for late gadolinium enhancement (LGE). The areas under the hierarchical modeling-based summary receiver-operating characteristic curve were 0.84 (95% CI: 0.81-0.87) for T1, 0.92 (95% CI: 0.89-94) for T2, 0.78 (95% CI: 0.74-0.81) for ECV, and 0.56 (95% CI: 0.51-0.60) for LGE. T2 values demonstrated the highest diagnostic accuracy, followed by native T1, ECV, and LGE (all P values <0.001 for T1, ECV, and LGE vs T2). CONCLUSIONS: T2 mapping demonstrated higher diagnostic accuracy than other CMR techniques. Native T1 and ECV provide high diagnostic use but lower diagnostic accuracy compared with T2, which was related primarily to lower specificity. LGE showed poor diagnostic performance for detection of rejection.

Concurrent smoking and alcohol consumers had higher triglyceride glucose indices than either only smokers or alcohol consumers: a cross-sectional study in Korea.

BACKGROUND: The triglyceride glucose (TyG) index is a noninsulin-based marker for insulin resistance (IR) in general practice. Although smoking and heavy drinking have been regarded as major risk factors for various chronic diseases, there is limited evidence regarding the combined effects of smoking and alcohol consumption on IR. This study aimed to investigate the relationship between the TyG index and smoking and alcohol consumption using two Korean population-based datasets. METHODS: This study included 10,568 adults in the Korean National Health and Nutrition Examination Survey (KNHANES) and 9586 adults in the Korean Initiatives on Coronary Artery Calcification (KOICA) registry datasets. Multivariate logistic analysis was conducted to explore the relationship between smoking and alcohol consumption and the TyG index. To assess the predictive value of smoking and alcohol consumption on high TyG index, the area under the curve (AUC) were compared and net reclassification improvement (NRI) and integrated discrimination improvement (IDI) analyses were derived. RESULTS: The combined effect of smoking and alcohol consumption was an independent risk factor of a higher TyG index in the KNHANES (adjusted odds ratio: 4.33, P < .001) and KOICA (adjusted odds ratio: 1.94, P < .001) datasets. Adding smoking and alcohol consumption to the multivariate logistic models improved the model performance for the TyG index in the KNHANES (AUC: from 0.817 to 0.829, P < .001; NRI: 0.040, P < .001; IDI: 0.017, P < .001) and KOICA (AUC: from 0.822 to 0.826, P < .001; NRI: 0.025, P = .006; IDI: 0.005, P < .001) datasets. CONCLUSIONS: Smoking and alcohol consumption were independently associated with the TyG index. Concurrent smokers and alcohol consumers were more likely to have a TyG index that was ≥8.8 and higher than the TyG indices of non-users and those who exclusively consumed alcohol or smoking tobacco.

Thoracic Aortic Calcium for the Prediction of Stroke Mortality (from the Coronary Artery Calcium Consortium).

Thoracic aortic calcium(TAC) is an important marker of extracoronary atherosclerosis with established predictive value for all-cause mortality. We sought to explore the predictive value of TAC for stroke mortality, independent of the more established coronary artery calcium (CAC) score. The CAC Consortium is a retrospectively assembled database of 66,636 patients aged ≥18 years with no previous history of cardiovascular disease, baseline CAC scans for risk stratification, and follow-up for 12 ± 4 years. CAC scans capture the adjacent thoracic aorta, enabling assessment of TAC from the same images. TAC was available in 41,066 (62%), and was primarily analyzed as present or not present. To account for competing risks for nonstroke death, we utilized multivariable-adjusted Fine and Gray competing risk regression models adjusted for traditional cardiovascular risk factors and CAC score. The mean age of participants was 53.8 ± 10.3 years, with 34.4% female. There were 110 stroke deaths during follow-up. The unadjusted subdistribution hazard ratio (SHR) for stroke mortality in those who had TAC present compared with those who did not was 8.80 (95% confidence interval [CI]: 5.97, 12.98). After adjusting for traditional risk factors and CAC score, the SHR was 2.21 (95% CI:1.39,3.49). In sex-stratified analyses, the fully adjusted SHR for females was 3.42 (95% CI: 1.74, 6.73) while for males it was 1.55 (95% CI: 0.83, 2.90). TAC was associated with stroke mortality independent of CAC and traditional risk factors, more so in women. The presence of TAC appears to be an independent risk marker for stroke mortality.

Association between blood pressure classification defined by the 2017 ACC/AHA guidelines and coronary artery calcification progression in an asymptomatic adult population.

Aims: Coronary artery calcium score (CACS) is widely used for cardiovascular risk stratification in asymptomatic population. We assessed the association of new blood pressure (BP) classification using the 2017 American College of Cardiology/American Heart Association guidelines with coronary artery calcification (CAC) progression according to age in asymptomatic adults. Methods and results: Overall, 10 839 asymptomatic Korean adults (23.4% aged ≤45 years) who underwent at least two CACS evaluations for health check-up were enrolled. Participants were categorized by age (≤45 and >45 years) and BP [normal (<120/<80 mmHg, untreated), elevated (120-129/<80 mmHg, untreated), Stage 1 hypertension (untreated BP 130-139/80-89 mmHg) or Stage 2 hypertension (BP ≥140/≥90 mmHg or anti-hypertensive use)] groups. CAC progression was defined as a difference of ≥2.5 between the square root (√) of the baseline and follow-up CACS. During a mean 3.3-year follow-up, the incidence of CAC progression was 13.5% and 36.3% in individuals aged ≤45 and >45 years, respectively. After adjustment for age, sex, diabetes, dyslipidaemia, obesity, current smoking, and baseline CACS, hazard ratios (95% confidence interval) for CAC progression in elevated BP, Stage 1 hypertension, and Stage 2 hypertension compared to normal BP were 1.43 (0.96-2.14) (P = 0.077), 1.64 (1.20-2.23) (P = 0.002), and 2.38 (1.82-3.12) (P < 0.001) in the ≤45 years group and 1.11 (0.95-1.30) (P = 0.179), 1.17 (1.04-1.32) (P = 0.009), and 1.52 (1.39-1.66) (P < 0.001) in the >45 years group, respectively. Conclusion: Newly defined Stage 1 hypertension is independently associated with CAC progression in asymptomatic adults regardless of age.

Independent association of serum uric acid levels with arterial stiffness in the absence of established cardiovascular disorders.

BACKGROUND: The impact of serum uric acid (SUA) on atherosclerosis has been suspected to be epiphenomenal owing to its close relationship with metabolic abnormalities. The aim of the present study was to evaluate the association between SUA levels and arterial stiffness in the absence of established cardiovascular (CV) disorders. METHODS: The relationship between SUA levels and brachial-ankle pulse wave velocity (baPWV) was examined in 353 asymptomatic adults (57 ± 8 years, 11.9% men) without established CV disorders defined as systolic blood pressure (BP) ≥140 mmHg or diastolic BP ≥ 90 mmHg; total cholesterol ≥240 mg/dL; low-density lipoprotein cholesterol ≥160 mg/dL; high-density lipoprotein cholesterol <40 mg/dL; fasting glucose ≥126 mg/dL; body mass index ≥25.0 kg/m2 ; current smoking; and history of medication for hypertension, diabetes, and dyslipidemia. Subjects were stratified into four groups based on the quartiles of their SUA levels. RESULTS: Mean baPWV was significantly different in all groups: group I, 1320 ± 195 cm/s; group II, 1336 ± 195 cm/s; group III, 1404 ± 199 cm/s; and group IV, 1483 ± 248 cm/s (P < .001). SUA levels were significantly correlated with baPWV (r = .364) (P < .001). Multivariate linear regression analysis showed that SUA (ß: 32.93; 95% confidence interval [CI]: 18.99-54.87), together with age (ß: 11.44; 95% CI: 9.36-13.53) and systolic BP (ß: 8.98; 95% CI: 6.80-11.16), was significantly associated with baPWV (P < .001). CONCLUSIONS: High SUA levels have an independent association with increased arterial stiffness even in subjects without established CV disorders.

Prognostic Value of Computed Tomography-Derived Extracellular Volume in TAVR Patients With Low-Flow Low-Gradient Aortic Stenosis.

OBJECTIVES: The association between extracellular volume (ECV) measured by computed tomography angiography (CTA) and clinical outcomes was evaluated in low-flow low-gradient (LFLG) aortic stenosis (AS) patients undergoing transcatheter aortic valve replacement (TAVR). BACKGROUND: Patients with LFLG AS comprise a high-risk group with respect to clinical outcomes. Although ECV, a marker of myocardial fibrosis, is traditionally measured with cardiac magnetic resonance, it can also be measured using cardiac CTA. The authors hypothesized that in LFLG AS, increased ECV may be associated with adverse clinical outcomes. METHODS: In 150 LFLG patients with AS who underwent TAVR, ECV was quantified using pre-TAVR CTA. Echocardiographic and clinical information including all-cause death and heart failure rehospitalization (HFH) was obtained from electronic medical records. A Cox proportional hazards model was used to evaluate the association between ECV and death+HFH. RESULTS: During a median follow-up of 13.9 months (range 0.07 to 28.9 months), there were 31 death+HFH events (21%). Patients who experienced death+HFH had a greater median Society of Thoracic Surgery score (9.9 vs. 4.7; p < 0.01), lower left ventricular ejection fraction (42.3 ± 20.2% vs. 52.7 ± 17.2%; p < 0.01), lower mean transvalvular gradient (24.9 ± 8.9 mm Hg vs. 28.1 ± 7.3 mm Hg; p = 0.04) and increased mean ECV (35.5 ± 9.6% vs. 29.9 ± 8.2%; p < 0.01) compared with patients who did not experience death+HFH. In a multivariable Cox proportional hazards model, increase in ECV was associated with increase in death+HFH, (hazard ratio per 1% increase: 1.04, 95% confidence interval: 1.01 to 1.09; p < 0.01). CONCLUSIONS: In patients with LFLG AS, CTA measured increase in ECV is associated with increased risk of adverse clinical outcomes post-TAVR and may thus serve as a useful noninvasive marker for prognostication.

Association of High-Density Calcified 1K Plaque With Risk of Acute Coronary Syndrome.

Importance: Plaque morphologic measures on coronary computed tomography angiography (CCTA) have been associated with future acute coronary syndrome (ACS). However, the evolution of calcified coronary plaques by noninvasive imaging is not known. Objective: To ascertain whether the increasing density in calcified coronary plaque is associated with risk for ACS. Design, Setting, and Participants: This multicenter case-control cohort study included individuals enrolled in ICONIC (Incident Coronary Syndromes Identified by Computed Tomography), a nested case-control study of patients drawn from the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry, which included 13 study sites in 8 countries. Patients who experienced core laboratory-verified ACS after baseline CCTA (n = 189) and control individuals who did not experience ACS after baseline CCTA (n = 189) were included. Patients and controls were matched 1:1 by propensity scores for age; male sex; presence of hypertension, hyperlipidemia, and diabetes; family history of premature coronary artery disease (CAD); current smoking status; and CAD severity. Data were analyzed from November 2018 to March 2019. Exposures: Whole-heart atherosclerotic plaque volume was quantitated from all coronary vessels and their branches. For patients who underwent invasive angiography at the time of ACS, culprit lesions were coregistered to baseline CCTA lesions by a blinded independent reader. Low-density plaque was defined as having less than 130 Hounsfield units (HU); calcified plaque, as having more than 350 HU and subcategorized on a voxel-level basis into 3 strata: 351 to 700 HU, 701 to 1000 HU, and more than 1000 HU (termed 1K plaque). Main Outcomes and Measures: Association between calcium density and future ACS risk. Results: A total of 189 patients and 189 matched controls (mean [SD] age of 59.9 [9.8] years; 247 [65.3%] were male) were included in the analysis and were monitored during a mean (SD) follow-up period of 3.9 (2.5) years. The overall mean (SD) calcified plaque volume (>350 HU) was similar between patients and controls (76.4 [101.6] mm3 vs 99.0 [156.1] mm3; P = .32), but patients who experienced ACS exhibited less 1K plaque (>1000 HU) compared with controls (3.9 [8.3] mm3 vs 9.4 [23.2] mm3; P = .02). Individuals within the highest quartile of 1K plaque exhibited less low-density plaque, as a percentage of total plaque, when compared with patients within the lower 3 quartiles (12.6% [10.4%] vs 24.9% [20.6%]; P < .001). For 93 culprit precursor lesions detected by CCTA, the volume of 1K plaque was lower compared with the maximally stenotic lesion in controls (2.6 [7.2] mm3 vs 7.6 [20.3] mm3; P = .01). The per-patient and per-lesion results were similar between the 2 groups when restricted to myocardial infarction cases. Conclusions and Relevance: Results of this study suggest that, on a per-patient and per-lesion basis, 1K plaque was associated with a lower risk for future ACS and that measurement of 1K plaque may improve risk stratification beyond plaque burden.

Identification and Quantification of Cardiovascular Structures From CCTA: An End-to-End, Rapid, Pixel-Wise, Deep-Learning Method.

OBJECTIVES: This study designed and evaluated an end-to-end deep learning solution for cardiac segmentation and quantification. BACKGROUND: Segmentation of cardiac structures from coronary computed tomography angiography (CCTA) images is laborious. We designed an end-to-end deep-learning solution. METHODS: Scans were obtained from multicenter registries of 166 patients who underwent clinically indicated CCTA. Left ventricular volume (LVV) and right ventricular volume (RVV), left atrial volume (LAV) and right atrial volume (RAV), and left ventricular myocardial mass (LVM) were manually annotated as ground truth. A U-Net-inspired, deep-learning model was trained, validated, and tested in a 70:20:10 split. RESULTS: Mean age was 61.1 ± 8.4 years, and 49% were women. A combined overall median Dice score of 0.9246 (interquartile range: 0.8870 to 0.9475) was achieved. The median Dice scores for LVV, RVV, LAV, RAV, and LVM were 0.938 (interquartile range: 0.887 to 0.958), 0.927 (interquartile range: 0.916 to 0.946), 0.934 (interquartile range: 0.899 to 0.950), 0.915 (interquartile range: 0.890 to 0.920), and 0.920 (interquartile range: 0.811 to 0.944), respectively. Model prediction correlated and agreed well with manual annotation for LVV (r = 0.98), RVV (r = 0.97), LAV (r = 0.78), RAV (r = 0.97), and LVM (r = 0.94) (p < 0.05 for all). Mean difference and limits of agreement for LVV, RVV, LAV, RAV, and LVM were 1.20 ml (95% CI: -7.12 to 9.51), -0.78 ml (95% CI: -10.08 to 8.52), -3.75 ml (95% CI: -21.53 to 14.03), 0.97 ml (95% CI: -6.14 to 8.09), and 6.41 g (95% CI: -8.71 to 21.52), respectively. CONCLUSIONS: A deep-learning model rapidly segmented and quantified cardiac structures. This was done with high accuracy on a pixel level, with good agreement with manual annotation, facilitating its expansion into areas of research and clinical import.

The association between progression of coronary artery calcium and colorectal adenoma: A retrospective follow-up study of asymptomatic Koreans.

The potential relationship between coronary artery calcium (CAC) and colorectal adenoma has been widely indicated. This study aimed to investigate the relationship between the risk of colorectal adenoma and CAC progression in asymptomatic Korean adults who underwent serial assessments by colonoscopy and CAC scan.A total of 754 asymptomatic participants, who had undergone serial CAC scans and colonoscopies for screening, were enrolled. Changes in CAC were assessed according to the absolute change between baseline and follow-up results. CAC progression was defined using Multi-Ethnic Study of Atherosclerosis method. Risk for adenoma at follow-up colonoscopy was determined using hazard ratio (HR) by Cox regression. The area under the receiver operating characteristic (ROC) curve was measured.The mean follow-up duration was 3.4 ± 2.5 years. CAC progression was found in 215 participants (28.5%). Participants with adenoma at index colonoscopy showed a higher rate of CAC progression than those without (38.8% vs 23.6%, P < .01). In participants with adenoma at index colonoscopy, CAC progression significantly increased the cumulative risk for adenoma at follow-up colonoscopy (HR = 1.48, 95% confidence interval [CI] 1.06-2.06, log-rank P = .021). In multivariate analysis, male sex (HR = 2.57, 95% CI 1.22-5.42, P = .013), ≥3 adenomas at index colonoscopy (HR = 2.60, 95% CI 1.16-5.85, P = .021), and CAC progression (HR = 2.74, 95% CI 1.48-5.08, P = .001) increased the risk of adenoma at follow-up colonoscopy. In participants without adenoma at index colonoscopy, neither baseline CAC presence nor CAC progression increased the risk of adenoma at follow-up colonoscopy. The interaction between CAC progression and adenoma at index colonoscopy was significant in multivariable model (P = .005). In the ROC analysis, AUC of CAC progression for adenoma at follow-up colonoscopy was 0.625 (95% CI 0.567-0.684, P < .001) in participants with adenoma at index colonoscopy.Participants with CAC progression, who are at high risk of coronary atherosclerosis, may need to be considered for follow-up evaluation of colorectal adenoma, especially those with adenoma at index colonoscopy.