Diabetes-Related Changes in Carotid Wall Properties: Role of Triglycerides.

Background/Objectives: This study compares the power of the radiofrequency (RF) signal reflected from the media layer (media power) of the common carotid artery (CCA) and the CCA stiffness between individuals with and without type 2 diabetes mellitus (T2DM). It also evaluates the associations of CCA media power with plasma glucose and lipid levels, as well as carotid stiffness. Methods: A total of 540 individuals, 115 with and 425 without T2DM (273 males, mean age = 64 ± 8 years) were studied using RF-based tracking of the right CCA. The following parameters were measured: CCA media thickness, luminal diameter, wall tensile stress (WTS), local pulse wave velocity (PWV), and media power. Results: Compared to the non-diabetic individuals, the T2DM patients had significantly higher CCA media thickness (652 ± 122 vs. 721 ± 138 microns, p < 0.005), luminal diameter (6.12 ± 0.78 vs. 6.86 ± 0.96 mm, p < 0.0005), media power (36.1 ± 4.8 vs. 39.3 ± 4.6, p < 0.0001), and PWV (7.65 ± 1.32 vs. 8.40 ± 1.89 m/s; p < 0.01), but comparable WTS (32.7 ± 10.4 vs. 33.1 ± 10.7 kPa; p = 0.25). In the entire population, CCA media power was independently associated with male sex, pulse pressure, current smoking, and T2DM; when T2DM was not included in the model, triglycerides emerged as an independent determinant of media power. The CCA PWV was independently associated with age, pulse pressure, media power, and T2DM. Conclusions: Our findings suggest the presence of structural changes in the arterial media of T2DM patients, leading to carotid stiffening and remodeling, aiming to preserve WTS. T2DM-related changes in arterial wall composition may be driven by high plasma triglyceride levels, which have previously been associated with both arterial stiffening and the incidence of CV events.

An ultrasound multiparametric method to quantify liver fat using magnetic resonance as standard reference.

BACKGROUND & AIMS: There is an unmet need for a reliable and reproducible non-invasive measure of fatty liver content (FLC) for monitoring steatotic liver disease in clinical practice. Sonographic FLC assessment is qualitative and operator-dependent, and the dynamic quantification range of algorithms based on a single ultrasound (US) parameter is unsatisfactory. This study aims to develop and validate a new multiparametric algorithm based on B-mode images to quantify FLC using Magnetic Resonance (MR) values as standard reference. METHODS: Patients with elevated liver enzymes and/or bright liver at US (N = 195) underwent FLC evaluation by MR and by US. Five US-derived quantitative features [attenuation rate(AR), hepatic renal-ratio(HR), diaphragm visualization(DV), hepatic-portal-vein-ratio(HPV), portal-vein-wall(PVW)] were combined by mixed linear/exponential regression in a multiparametric model (Steatoscore2.0). One hundred and thirty-four subjects were used for training and 61 for independent validations; score-computation underwent an inter-operator reproducibility analysis. RESULTS: The model is based on a mixed linear/exponential combination of 3 US parameters (AR, HR, DV), modelled by 2 equations according to AR values. The computation of FLC by Steatoscore2.0 (mean ± std, 7.91% ± 8.69) and MR (mean ± std, 8.10% ± 10.31) is highly correlated with a low root mean square error in both training/validation cohorts, respectively (R = 0.92/0.86 and RMSE = 5.15/4.62, p < .001). Steatoscore2.0 identified patients with MR-FLC≥5%/≥10% with sensitivity = 93.2%/89.4%, specificity = 86.1%/95.8%, AUROC = 0.958/0.975, respectively and correlated with MR (R = 0.92) significantly (p < .001) better than CAP (R = 0.73). CONCLUSIONS: Multiparametric Steatoscore2.0 measures FLC providing values highly comparable with MR. It is reliable, inexpensive, easy to use with any US equipment and qualifies to be tested in larger, prospective studies as new tool for the non-invasive screening and monitoring of FLC.

Late plasma exosome microRNA-21-5p depicts magnitude of reverse ventricular remodeling after early surgical repair of primary mitral valve regurgitation.

Introduction: Primary mitral valve regurgitation (MR) results from degeneration of mitral valve apparatus. Mechanisms leading to incomplete postoperative left ventricular (LV) reverse remodeling (Rev-Rem) despite timely and successful surgical mitral valve repair (MVR) remain unknown. Plasma exosomes (pEXOs) are smallest nanovesicles exerting early postoperative cardioprotection. We hypothesized that late plasma exosomal microRNAs (miRs) contribute to Rev-Rem during the late postoperative period. Methods: Primary MR patients (n = 19; age, 45-71 years) underwent cardiac magnetic resonance imaging and blood sampling before (T0) and 6 months after (T1) MVR. The postoperative LV Rev-Rem was assessed in terms of a decrease in LV end-diastolic volume and patients were stratified into high (HiR-REM) and low (LoR-REM) LV Rev-Rem subgroups. Isolated pEXOs were quantified by nanoparticle tracking analysis. Exosomal microRNA (miR)-1, -21-5p, -133a, and -208a levels were measured by RT-qPCR. Anti-hypertrophic effects of pEXOs were tested in HL-1 cardiomyocytes cultured with angiotensin II (AngII, 1 µM for 48 h). Results: Surgery zeroed out volume regurgitation in all patients. Although preoperative pEXOs were similar in both groups, pEXO levels increased after MVR in HiR-REM patients (+0.75-fold, p = 0.016), who showed lower cardiac mass index (-11%, p = 0.032). Postoperative exosomal miR-21-5p values of HiR-REM patients were higher than other groups (p < 0.05). In vitro, T1-pEXOs isolated from LoR-REM patients boosted the AngII-induced cardiomyocyte hypertrophy, but not postoperative exosomes of HiR-REM. This adaptive effect was counteracted by miR-21-5p inhibition. Summary/Conclusion: High levels of miR-21-5p-enriched pEXOs during the late postoperative period depict higher LV Rev-Rem after MVR. miR-21-5p-enriched pEXOs may be helpful to predict and to treat incomplete LV Rev-Rem after successful early surgical MVR.

Big and Free Fractions of Gamma-Glutamyltransferase: New Diagnostic Biomarkers for Malignant Mesothelioma?

Malignant pleural mesothelioma (MPM) is a cancer mainly caused by asbestos fiber inhalation, characterized by an extremely long latency and poor prognosis. Recently, researchers have focused on testing the diagnostic ability of several biomarkers. Gamma-Glutamyltransferase (GGT) has been demonstrated to be the sum of several GGT sub-fractions activity, classified based on their molecular weight in big-GGT, medium-GGT, small-GGT, and free-GGT. This work aims to evaluate whether specific GGT fractional enzymatic activity patterns could be helpful in MPM diagnosis. We analyzed blood samples from 175 workers previously exposed to asbestos, 157 non-exposed healthy subjects, and 37 MPM patients through a molecular exclusion chromatographic method. We found a specific profile of GGT fractions activity, significantly associated with MPM, resulting in an increase in b-, m- activity, along with an evident, yet not significant, decrease in f-activity. Receiver-operating characteristic (ROC) analysis showed that the best Area Under Curve (AUC) value resulted from the combined index b/f (0.679, 95% CI: 0.582-0.777). Combining the b-/f-GGT activity with the levels of serum mesothelin-related protein (SMRP; another promising MPM biomarker) improved the diagnostic accuracy, increasing the AUC value to 0.875 (95% CI: 0.807-0.943, p = <0.0001). Since MPM has a specific pattern of GGT enzymatic activity, we could hypothesize that GGT fractions play different specific biochemical roles. The improvement in the diagnostic power given by the combination of these two biomarkers confirms that the strategy of biomarkers combination might be a better approach for MPM diagnosis.

Big gamma-glutamyltransferase is associated with epicardial fat volume and cardiovascular outcome in the general population.

AIMS: Gamma-glutamyltransferase (GGT) has been recognized as a cardiovascular risk factor, and its highest molecular weight fraction [big GGT (b-GGT)] is found in vulnerable atherosclerotic plaques. We explored the relationship between b-GGT, computed tomography findings, and long-term outcomes in the general population. METHODS AND RESULTS: Between May 2010 and October 2011, subjects aged 45-75 years living in a Tuscan city and without known cardiac disease were screened. The primary endpoint was a composite of cardiovascular death or acute coronary syndrome requiring urgent coronary revascularization. Gamma-glutamyltransferase fractions were available in 898 subjects [median age 65 years (25th-75th percentile 55-70), 46% men]. Median plasma GGT was 20 IU (15-29), and b-GGT was 2.28 (1.28-4.17). Coronary artery calcium (CAC) score values were 0 (0-60), and the volume of pro-atherogenic epicardial fat was 155 mL (114-204). In a model including age, sex, low-density lipoprotein (LDL) cholesterol, current or previous smoking status, hypertension, diabetes, obesity, b-GGT independently predicted epicardial fat volume (EFV) (r = 0.162, P < 0.001), but not CAC (P = 0.198). Over a 10.3-year follow-up (9.6-10.8), 27 subjects (3%) experienced the primary endpoint. We evaluated couples of variables including b-GGT and a cardiovascular risk factor, CAC or EFV. Big GGT yielded independent prognostic significance from age, LDL cholesterol, current or previous smoking status, hypertension, diabetes, obesity, but not CAC or EFV. Conversely, GGT predicted the primary endpoint even independently from CAC and EFV. CONCLUSION: Big GGT seemed at least as predictive as the commonly available GGT assay; therefore, the need for b-GGT rather than GGT measurement should be carefully examined.

Patient Perceptions and Knowledge of Ionizing Radiation From Medical Imaging.

Importance: Although imaging has become a standard tool of modern medicine, its widespread use has been paralleled by an increasing cumulative radiation dose to patients despite technological advancements and campaigns calling for better awareness and minimization of unnecessary exposures. Objective: To assess patients' knowledge about medical radiation and related risks. Design, Setting, and Participants: A survey study of hospitals in Italy was conducted; all patients in waiting rooms for medical imaging procedures before undergoing imaging examinations at 16 teaching and nonteaching hospitals were approached to take the survey. The survey was performed from June 1, 2019, to May 31, 2020. Main Outcomes and Measures: Survey respondents' basic knowledge of ionizing radiation levels and health risks, earlier imaging tests performed, and information and communication about radiation protection issues. Results: Among 3039 patients invited to participate, the response rate was 94.3% (n = 2866). Participants included 1531 women (53.4%); mean (SD) age was 44.9 (17.3) years. Of the 2866 participants, 1529 (53.3%) were aware of the existence of natural sources of ionizing radiation. Mammography (1101 [38.4%]) and magnetic resonance imaging (1231 [43.0%]) were categorized as radiation-based imaging modalities. More than half of the 2866 patients (1579 [55.1%]; P = .03) did not know that chest computed tomography delivers a larger dose of radiation than chest radiography, and only 1499 (52.3%) knew that radiation can be emitted after nuclear medicine examinations (P = .004). A total of 667 patients (23.3%) believed that radiation risks were unrelated to age, 1273 (44.4%) deemed their knowledge about radiation risks inadequate, and 2305 (80.4%) preferred to be informed about radiation risks by medical staff. A better knowledge of radiation issues was associated with receiving information from health care professionals (odds ratio [OR], 1.71; 95% CI, 1.43-2.03; P < .001) and having a higher educational level (intermediate vs low: OR, 1.48; 95% CI, 1.17-1.88; P < .001; high vs low: OR, 2.68; 95% CI, 2.09-3.43; P < .001). Conclusions and Relevance: The results of this survey suggest that patients undergoing medical imaging procedures have overall limited knowledge about medical radiation. Intervention to achieve better patient awareness of radiation risks related to medical exposures may be beneficial.

Pitfalls in surgical repair of Fallot's tetralogy: The "ventricular subaortic pouch".

Fallot-type ventricular septal defect (VSD) is characterized by anterior malalignment of the outlet septum with variable degree of aortic dextroposition. Correct identification of the borders of the defect is crucial to achieve an optimal surgical repair. We describe a particular postsurgical lesion, identified by cardiac magnetic resonance and cardiac computed tomography, which results from an improper surgical closure technique of anterior malaligned VSD. Based on its anatomical features we defined this entity "subaortic pouch." A comprehensive description of this defect is here provided along with an in-depth analysis of the proper operative technique for Fallot-type VSD repair.

Deep learning to diagnose cardiac amyloidosis from cardiovascular magnetic resonance.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is part of the diagnostic work-up for cardiac amyloidosis (CA). Deep learning (DL) is an application of artificial intelligence that may allow to automatically analyze CMR findings and establish the likelihood of CA. METHODS: 1.5 T CMR was performed in 206 subjects with suspected CA (n = 100, 49% with unexplained left ventricular (LV) hypertrophy; n = 106, 51% with blood dyscrasia and suspected light-chain amyloidosis). Patients were randomly assigned to the training (n = 134, 65%), validation (n = 30, 15%), and testing subgroups (n = 42, 20%). Short axis, 2-chamber, 4-chamber late gadolinium enhancement (LGE) images were evaluated by 3 networks (DL algorithms). The tags "amyloidosis present" or "absent" were attributed when the average probability of CA from the 3 networks was ≥ 50% or < 50%, respectively. The DL strategy was compared to a machine learning (ML) algorithm considering all manually extracted features (LV volumes, mass and function, LGE pattern, early blood-pool darkening, pericardial and pleural effusion, etc.), to reproduce exam reading by an experienced operator. RESULTS: The DL strategy displayed good diagnostic accuracy (88%), with an area under the curve (AUC) of 0.982. The precision (positive predictive value), recall score (sensitivity), and F1 score (a measure of test accuracy) were 83%, 95%, and 89% respectively. A ML algorithm considering all CMR features had a similar diagnostic yield to DL strategy (AUC 0.952 vs. 0.982; p = 0.39). CONCLUSIONS: A DL approach evaluating LGE acquisitions displayed a similar diagnostic performance for CA to a ML-based approach, which simulates CMR reading by experienced operators.

Convolutional Neural Networks for the Segmentation of Microcalcification in Mammography Imaging.

Cluster of microcalcifications can be an early sign of breast cancer. In this paper, we propose a novel approach based on convolutional neural networks for the detection and segmentation of microcalcification clusters. In this work, we used 283 mammograms to train and validate our model, obtaining an accuracy of 99.99% on microcalcification detection and a false positive rate of 0.005%. Our results show how deep learning could be an effective tool to effectively support radiologists during mammograms examination.

Effect of iodinated contrast medium on thyroid function: a study in children undergoing cardiac computed tomography.

BACKGROUND: Few studies, and with conflicting results, have evaluated the potential effects of iodinated contrast media on children's thyroid function. OBJECTIVE: To investigate the effects of iodinated contrast medium on thyroid function in neonates, infants and young children with congenital heart disease undergoing cardiac computed tomography (CT). MATERIALS AND METHODS: We retrospectively evaluated 10 neonates (group 1) and 23 infants and young children (group 2) without thyroid or renal disease for serum levels of thyroid-stimulating hormone, free triiodothyronine and free thyroxine before contrast-enhanced cardiac CT, 48 h after CT and at discharge from the hospital. Cardiac CT was performed with intravenous administration of 1.14±0.17 mL/kg of body weight of iopromide (containing 370 mg of iodine/mL). RESULTS: Group 1 had a reduction of thyroid-stimulating hormone from baseline to 48 h post injection (P=0.002). Group 2 had a reduction of thyroid-stimulating hormone median levels from baseline to 48 h post injection and an increase from 48 h to discharge (P=0.0005 and P=0.0001, respectively). CONCLUSION: Intravenous iodinated contrast medium in children with congenital heart disease caused transient thyroid-stimulating hormone decrease 48 h after CT, with thyroid-stimulating hormone returning to normal range at discharge.

Impact of 3D printing on the surgical management of tracheal stenosis associated to pulmonary sling: a case report.

Congenital tracheal stenosis (CTS) is rare lesions frequently associated with pulmonary sling (PS). Despite the recent improvement in the results by the introduction of slide tracheoplasty (ST) and multidisciplinary approach, surgical management remains difficult and several authors, for this reason, debate for a conservative approach in these cases. Preoperative planning, require hence the use of the most innovative technology to gain the best possible result. This report describes a complicated, unsuccessful surgically treated case of CTS associated to PS. Based on this result and in order to improve the outcomes, we have built a 3D model of patient's trachea simulating preoperative surgical planning. We have hypnotized that having the model preoperatively the choice of surgical technique would have been different. Since that case, 3D models are introduced in our practice and built before tracheal or cardiac cases considered to have complex anatomy. Future investigations are required but at the moment this experience confirms the utility of 3D model in the evaluation of children considered for tracheal surgery.

Increased Gradients After Aortic Valve Replacement With the Perceval Valve: The Role of Oversizing.

BACKGROUND: Significant underexpansion or distortion of valved stents may be associated with altered leaflet function, leading to increased transprosthetic gradients and, possibly, early structural degeneration. We investigated the relationship between a computed tomography measure of the degree of oversizing and the early hemodynamic and clinical outcomes in patients undergoing aortic valve replacement with the Perceval sutureless aortic valve (LivaNova, Saluggia, Italy). METHODS: The degree of oversizing of the implanted prosthesis was calculated as the ratio between the patients' aortic annulus cross-sectional area and the ex vivo cross-sectional area of the implanted prosthesis in 151 Perceval patients who underwent preoperative cardiac computed tomography. This value was then entered in a multivariate analysis to ascertain its role as a predictor of increased postoperative gradient. RESULTS: The operative mortality was 1.3%. Procedural success, defined as having a normally functioning valve in the proper anatomical location, was achieved in 150 patients (99.3%). The mean transprosthetic gradient was 13.4 ± 5.0 mm Hg, and 23 patients (15.2%) showed a gradient of 20 mm Hg or more at discharge or at the 1-month follow-up. The degree of oversizing of the implanted prosthesis was the most important predictor of increased postoperative gradient (odds ratio, 1.264; 95% confidence interval, 1.147 to 1.394; p < 0.0001). Interestingly, other relevant factors (patients' body surface area, prosthesis size) were not associated with increased gradients. CONCLUSIONS: Our study demonstrates that excessive oversizing should be avoided in Perceval patients and suggests that a different sizing algorithm, possibly based on cardiac computed tomography, should be developed. Further studies are needed to optimize the sizing strategy for the Perceval sutureless valve.

A multimarker study of degenerative aortic valve disease: stenoinsufficiency shows more indices of bad prognosis.

OBJECTIVES: It was the aim of this study to assess the pathophysiological, prognostic role of aortic regurgitation (AR) in the 'mixed pictures' of degenerative aortic valve stenoinsufficiency (ASI) by a multimarker clinical approach. METHODS: We enrolled 112 consecutive surgical PATIENTS: 19 with pure valve stenosis (PAS), 39 with mild regurgitation, 29 with severe regurgitation, and 25 controls with annulo-ectatic AR. All underwent complete echocardiography, carotid ultrasound and aortic/coronary multislice computed tomography calcium score evaluation. We determined tissue semiquantitative osteopontin, metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMPs) and circulating brain natriuretic peptide. We evaluated major adverse cardiac events and cardiovascular early, long-term mortality after bioprosthetic valve implantation. RESULTS: Tissue calcification, carotid and coronary atherosclerotic disease were prevalent in PAS versus ASI and AR patients. The multislice computed tomography calcium score (Agatston) was comparable between PAS and ASI (PAS 3,507.3 + 2,442.6; mild AR 4,270.7 + 2,213.5; severe AR 3,568.5 + 1,823.4), but much lower in AR (1,247.8 + 2,708.6). In ASI, a plasma/tissue 'profibrotic' MMP/TIMP balance prevailed, with circulating and echocardiographic indices of myocardial dysfunction. Percentages of major adverse cardiac events and early, long-term mortality were higher in ASI. CONCLUSIONS: In ASI, different, still unknown, genetic and dysplastic factors could work synergically with cardiovascular risk factors, determining a much more adverse myocardial and valve remodeling, resulting in worse clinical outcome.

Endovascular treatment of acute thoracic aortic syndromes with a proximal landing zone extension strategy: procedural and follow-up results.

PURPOSE: To report the procedural and long-term follow-up data (mean, 43 ± 29 months; range, 12-90 months) of endovascular stent grafting (ESG) of acute thoracic aortic syndromes (ATAS) with a proximal landing zone extension strategy. METHODS: From November 1999 to May 2008, 26 patients (25 males, 1 female; mean age, 57.9 ± 17 years) with ATAS underwent ESG at our institution. Underlying pathologies were: penetrating aortic ulcer (n=7); rupture of a descending aorta aneurysm (n=5), post-traumatic false aneurysm (n=5); acute type B dissection (n=6) and traumatic descending aorta transection (n=3). RESULTS: ESG was performed successfully in all patients. In 5 patients (19%), an extra-anatomic revascularization of the supra-aortic vessels was performed. In 19 patients (73%), overstenting of the left subclavian artery, without preliminary revascularization, was performed. The mean proximal landing zone length was 57 ± 19 mm. No intraprocedural deaths occurred; 3 patients died postoperatively (1 from an unrelated cause, 1 from a myocardial infarction and 1 for the sequelae of an ischemic stroke). One patient underwent cardiac surgery for post-procedural retrograde type-A dissection. Follow up involved a computed tomography (CT) scan at 1, 3, 6 and 12 months, then yearly thereafter. At follow up, no deaths or major complications occurred. The CT scans revealed 1 small type-IB endoleak at 1 year. CONCLUSION: In ATAS patients treated with ESG, the extension of the proximal landing zone, despite the need of subclavian coverage or hybrid procedures, is associated with an immediate procedural outcome and low morbidity at follow-up.

Circulating soluble receptor for advanced glycation end-product levels are decreased in patients with calcific aortic valve stenosis.

OBJECTIVE: It has been suggested that atherosclerotic mechanisms are involved in the pathogenesis of aortic valve stenosis (AVS). We hypothesised that low levels of the soluble receptor for advanced glycation end-products (sRAGE) might be associated with AVS due to its clinical and pathological associations with atherosclerosis. METHODS: We enrolled 75 consecutive patients with severe AVS scheduled for surgical aortic valve replacement and 39 controls without AVS matched for age and gender. Besides the traditional risk factors, we evaluated plasma levels of sRAGE, C-reactive protein (CRP) and IL-6. All patients underwent transthoracic echocardiography, carotid arteries ultrasound scan and coronary angiography. The aortic and coronary calcium by multislice computed tomography was assessed in AVS patients. RESULTS: The values of sRAGE were significantly lower (p<0.01) in AVS patients than in controls, while the CRP levels were significantly higher (p<0.05) in AVS patients than in controls. In AVS patients the sRAGE levels correlated inversely with age, cholesterol levels and coronary calcification. In all study subjects, we found an inverse correlation between circulating sRAGE and the number of echographically assessed sites of calcification (ANOVA, p<0.0001). In multivariable logistic regression analysis after adjustment for potential confounders, the sRAGE levels were significantly and independently associated with the risk of AVS (OR=0.997, 95% CI=0.994-1.000, p=0.048). CONCLUSION: Since sRAGE could exert antiatherogenic effects by preventing inflammatory responses mediated by cell surface RAGE activation, low levels in AVS patients indicate that ligand-RAGE axis could contribute to pathogenesis of AVS.