Calcium Volume Research Articles

Breast arterial calcification and epicardial adipose tissue volume, but not density are independently associated with cardiovascular risk

BackgroundMammographically detected breast arterial calcification (BAC) has been proposed as surrogate marker for coronary artery disease (CAD) in women. Epicardial adipose tissue (EAT) and peri-coronary adipose tissue (PCAT) are inflammatory fat depots linked to atherogenesis. BAC has demonstrated association with inflammation, therefore we aimed to determine the association between BAC, EAT and PCAT. MethodsSingle-centre, retrospective, cross-sectional study of women with digital mammography and coronary computed tomography angiography (CCTA). EAT and PCAT were quantitively assessed using semi-automated software. Patient demographics and cardiovascular risk factors were obtained from medical records and mammograms reviewed for BAC. Pre-test cardiovascular risk was determined with CAD Consortium Score. Chi-square, t-test and Mann-Whitney U tests were used to assess between group differences. Multivariable linear and logistic regression modelling was conducted to adjust for confounders. ResultsAmong 153 patients (age 61, SD 11) included in this study, BAC was present in 37 (24%) patients. BAC-positive patients had higher EAT volume (EATv) (110.2 mL, SD 41 mL vs 94.4 mL, SD 41 mL, p = 0.02) but this association was not significant after adjusting for cardiovascular risk factors (p = 0.26). BAC did not associate with EAT density or PCAT. BAC and EATv were strongly associated with cardiovascular risk and CAD independent of each other: CV risk (BAC OR 7.55 (3.26–18.49), p < 0.001, EATv OR 1.02 (1.01–1.03), p < 0.001), CAD presence (BAC OR 4.26 (1.39–13), p = 0.01; EATv OR 1.01 (1.0–1.03), p = 0.04). ConclusionBAC and EATv are independent predictors of CV risk and CAD, but don't independently associate with each other, the relationship confounded by shared cardiovascular risk factors. BAC doesn't appear to associate with adipose tissue density and its presence may be cumulative result of long-term exposure to CV risk factors.

Coronary artery calcium incidence and changes using direct plaque measurements: The MASALA study

Background and aimsWe aimed to identify predictors of change in direct measures of coronary artery calcium (CAC) volume and density in South Asian participants. MethodsWe used data from participants in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study with prevalent CAC and direct measures of CAC by serial computed tomography (CT) exams (2010–2013, 2016–2018). We examined the distribution of incident CAC volume and peak density, as well as progression and identified risk factors for progression of change in volume and density in multivariable models. ResultsThe study cohort consisted of 102 participants with incident CAC and 285 with CAC progression. CAC volume and density were highest, and incident CAC was most common in the left anterior descending artery (LAD). The greatest progression in volume was in the right coronary artery and the greatest change in density was in the left main. In linear regression models for CAC progression adjusted for baseline density, volume, risk factors, smoking (β +190.1, p = 0.02), baseline volume (β +0.24 per mm3, p < 0.01), and scan interval (β +0.15 per day, p = 0.01) were associated with change in total volume whereas Lp(a) (β +0.81 per mg/dL, p = 0.03), exercise (β +0.19 per 10 MET-min/week, p = 0.01), and baseline volume (β +0.15 per mm3, p < 0.01) and density (β −0.55 per unit, p < 0.01) were associated with change in total density. ConclusionsIn this South Asian cohort, smoking was associated with CAC volume progression, while Lp(a) and exercise were associated with progression of peak CAC density.

Association between vascular calcification in intracranial vertebrobasilar circulation and luminal stenosis

The study aims to assess the correlation and association between calcium burden and luminal stenosis in the vertebrobasilar circulation. We evaluated 166 patients [mean age, 79.8 ± 8.8 (SD) with 93 males] with stroke symptoms. The calcification patterns were assessed on non-contrast CT (NCCT); quantitative calcium burden [Agatston-Janowitz (AJ) calcium score, volume, and mass] on the initial non-contrast phase of CT perfusion (CTP); and the qualitative and quantitative luminal stenosis on CT angiography (CTA) studies. We calculated the correlation coefficient and association between measures of calcium burden and luminal stenosis. Two hundred twenty-eight of 498 arteries (45.8%) had detectable calcification on NCCT and measurable stenosis in 169 of 498 arteries (33.9%) on CTA. We found a moderate correlation between qualitative calcium burden and qualitative (0.51 for R1 and 0.62 for R2, p < 0.01) as well as quantitative luminal stenosis (0.67 for R1 and 0.69 for R2, p < 0.01). There was a moderate correlation of AJ score (0.66), volume (0.68), and mass of calcification (0.60, p < 0.01) with luminal stenosis measurements. The quantitative calcium burden and luminal stenosis showed statistically significant differences between different qualitative categories of calcium burden (p < 0.001 in both readers). However, severe stenosis was not seen even with the advanced circumferential wall calcification (mean stenosis of 35.3-40.7%). Our study showed a moderate correlation between higher burden of vascular calcification and the degree of luminal stenosis. However, higher calcium burden and circumferential wall calcification were not associated with severe luminal stenosis.

MO905: Calcification of Branches is Superior to Abdominal Aortic Calcification in Predicting Mortality of Hemodialysis Patients

Abstract BACKGROUND AND AIMS Vascular calcification (VC) is considered to be an important initiating risk factor of cardiovascular events, which contributes to the leading cause of death in maintenance hemodialysis (MHD) patients. VC has a high incidence and has been reported to predict the mortality of MHD patients. Inspired by an extreme example of VC in dialysis patients, calciphylaxis (which involves extensive calcification of small- and medium- arteries with poor prognosis), we hypothesized that VC of branches was a better predictor of mortality than abdominal aortic calcification. Therefore, a cohort study based on MHD patients was constructed to investigate the distribution characteristics of VC, compare the predictive value of VC on mortality among different arteries, and explore a comprehensive model predicting mortality. METHOD A total of 1583 patients in our Blood Purification Center from January 2015 to September 2017 were screened, and 237 eligible patients were finally included. Abdominal-pelvic computed tomography images were collected and an open-source software 3D Slicer (version 4.11) was used to calculate the calcification volume in abdominal aorta, celiac trunk, superior and inferior mesenteric artery, renal artery, common iliac artery and internal iliac artery. Demographic and clinical data including medical history and some laboratory indexes were collected. Patients were followed-up until all-cause death or September 2020. Cause of death and survival time were recorded in detail. The area under the curve (AUC) of Time-dependent receiver operating curves (ROC) was calculated to evaluate the predictive value of arterial calcification. 80% of cases were randomly assigned to the training dataset and the remaining were assigned to the validation dataset. Lasso regression was performed to screen variables. Cox proportional hazards regression was performed to construct the predicting model and nomogram. C-index, calibration and decision curve analysis were used to evaluate the comprehensive model. SPSS software (version 26.0) and R software (version 4.1.2) perform statistical analysis. RESULTS The prevalence of total VC is 95.36%. Among the abdominal arteries, abdominal aortic calcification is the most prevalent (88.61%), followed by calcification of internal iliac artery (85.65%) and common iliac artery (80.17%). Median survival time was 37.00 (1.00–70.00) months. The 1-year survival rate, 3-year survival rate and 5-year survival rate were 73.42%, 50.01% and 35.43%, respectively. Cardiovascular disease accounts for 54.01% of the death cause. AUC of Time-dependent ROC by internal iliac artery and mesenteric artery calcification for predicting mortality is significantly higher than that of other arterial calcification. Internal iliac artery calcification (IIAC) was screened out as the most representative predictor for all-cause death among the calcification of arterial calcification by lasso regression. When analyzing IIAC and other clinical data, age (hazard ratio 1.03, P &amp;lt; 0.001), serum albumin level (hazard ratio 0.919, P &amp;lt; 0.001) and IIAC (hazard ratio 1.36, P = 0.003) were independent factor of mortality in HD patients. The nomogram based on Cox proportional hazards model is shown in Figure 1. C-index of the model was 74.09%. Decision curves of Cox proportional hazards model from training dataset and validation dataset showed the reliable predictive value of Cox model (Figure 2). CONCLUSION This is the first study evaluating the calcification volume of abdominal aortic branches and comparing their predictive values. In conclusion, calcification of abdominal aortic branches, especially internal iliac artery, is a better predictor for mortality of HD patients than abdominal aortic calcification. Our concern with calcification of large arteries in MHD patients needs to be shifted to smaller branch arteries.

MO185: Post-Translational Carbamylation of Sortilin is Associated with Cardiovascular Calcification in Chronic Kidney Disease

Abstract BACKGROUND AND AIMS Sortilin, an intracellular sorting receptor, has been identified as a cardiovascular (CV) risk factor in the general population. Patients with chronic kidney disease (CKD) are highly susceptible to developing CV complications such as CV calcification. However, specific CKD-induced post-translational protein modifications of sortilin and their link to CV calcification remain unknown. METHODS Circulating sortilin isolated from two independent CKD cohorts was analysed by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF mass spectrometry). The binding partner affinity was analysed by surface plasmon resonance spectroscopy. The effect of carbamylated sortilin on vascular calcification was analysed in vitro using human coronary artery smooth muscle cells. RESULTS In CKD patients, targeted mass spectrometric analyses of circulating sortilin revealed an increase in carbamylated lysine residues with kidney function decline. Carbamylation did not affect dimer formation of sortilin assessed by mass spectrometry. We observed an increased affinity of interleukin 6 to in vitro carbamylated sortilin. Carbamylated sortilin increased SMC calcification in vitro that was accelerated by interleukin 6, while carbamylated albumin and collagen type I did not affect SMC calcification. Mass-spectrometry imaging of human calcified arteries revealed in situ carbamylated sortilin. In CKD patients, sortilin carbamylation was associated with coronary artery calcification volume, independent of age, kidney function and other risk factors. Moreover, patients with carbamylated sortilin displayed significantly faster coronary artery calcification progression than patients without sortilin carbamylation. CONCLUSION Carbamylated sortilin is a risk factor for CV calcification and may contribute to elevated CV complications in patients with CKD.

MO734: High Serum Oxalate Concentration Associated with Coronary Artery Calcification and Lanthanum Carbonate in Hemodialysis Patients

Abstract BACKGROUND AND AIMS Oxalate is an organic acid found in abundance in plants and can also be synthesized as a terminal metabolite by the organic acid metabolism systems in humans. As a major excretion pathway of oxalate is urine, serum oxalate (SOx) concentration elevates in end-stage renal disease (ESRD) patients and causes calcium oxalate deposition to tissues. We previously reported that calcium oxalate might be one of the major components of coronary artery calcification (CAC) in ESRD patients; however, the association between SOx and CAC is unknown. This study aimed to demonstrate the relationship between SOx and CAC in haemodialysis patients. METHOD A total of 77 patients undergoing maintenance haemodialysis at a single facility who underwent an atherosclerosis check-up from 2011 to 2012 were enrolled and measured SOx retrospectively in 2021. Of those, 17 extremely outlying SOx patients were excluded, and 60 patients including 42 males were analysed. The median age was 64 (35–85) years, and median dialysis duration was 87.5 (17.1–410) months. Gender, Agastston's CAC score, major artery calcification volume, laboratory data and medications around the atherosclerosis check-up date and new-onset cardiovascular disease (CVD) events and deaths during the 10-year observation period were recorded. A CVD event is defined as an admission due to non-fatal myocardial infarction, coronary artery disease or heart failure. SOx level was measured by the commercial colorimetric oxalate assay kit, and the normal SOx level was 181 µmol/L. RESULTS The median SOx was 267 (221–563) µmol/L and new-onset CVD events, all-cause deaths occurred in 28 (47%) and 22 (37%) patients, respectively. In univariate analysis, SOx was associated with males (r = 0.27, P = 0.03), serum albumin (r = –0.25, P = 0.05), uric acid (r = 0.29, P = 0.02), phosphate (r = 0.26, P = 0.04), alkaline phosphatase (r = –0.28, P = 0.03), lanthanum carbonate (r = 0.32, P = 0.01), major artery calcification volume (r = 0.28, P = 0.03) and CAC score (r = 0.29, P = 0.02). In multivariate regression analysis, SOx was associated with lanthanum carbonate (F = 5.96, P = 0.02) and CAC score (F = 4.47, P = 0.03, Table 1). Receiver operating characteristic curve showed SOx = 269.5 µmol/L was the best cut-off for predicting CVD events. We divided subjects into two groups by this cut-off SOx value and revealed SOx was associated with new-onset CVD events (N = 60, P = 0.01) even after adjusted by age under 75 years (N = 52, P = 0.03) or both age under 75 years and CAC score under 1000 (N = 28, P = 0.04) by the Kaplan–Meier method (Fig. 1). CONCLUSION SOx was associated with CAC score, lanthanum carbonate and CVD events in ESRD patients undergoing haemodialysis.

Abstract 186: Anatomically Indexed Distributions Of Aortic Calcification In A Reference Population

Introduction: Cardiovascular disease remains the leading cause of death in the United States. Aortic calcification shows strong promise towards preventative screening efforts for cardiovascular risk in clinical and subclinical populations. While still relatively novel, granular distributions of aortic calcium in reference populations are absent from the literature. Methods: All participants of the Reference Analytic Morphomics Population, an approximation of vehicle occupants in the United States, with abdominal scans were considered for this analysis (n=4080). Analytic Morphomics was used to obtain vertebral-indexed anatomical measurements of the aorta and calcium characteristics (area, volume, density, and aortic wall obfuscation). Calcification was specifically identified as regions with a given morphology and pixel value three standard deviations above the defined central lumen zone. Results: Participant mean age was 33 (SD 22.6) and were mostly male (62.6%) due to the prevalence of males involved in trauma. Age and calcification distributions were right skewed among all vertebral levels and highest for the L3-L4 reference levels [~3% wall obfuscation (SD 10.5-11.3)]. Males demonstrated a progressive increase in total calcium volume from the 4 th decade of age, while females had comparatively smaller increases and a dramatic increase in total calcium after the 7 th decade. The largest increases in observed calcium volumes were observed in the 8 th decade for males (~2300 cm 3 ) and 7 th for females (~4500 cm 3 ). Conclusion: Aortic calcium prevalence was higher with reference to lower vertebral levels. Dramatic differential distributions of calcium were observed by age and sex.

Major adverse cardiovascular events in bulgarian patients with chronic coronary syndrome.

In primary prevention, most guidelines rely on atherosclerotic cardiovascular disease risk assessment to determine the appropriateness and intensity of risk factor modification. This study aimed to analyze the prognostic role of risk factors, comorbidities, and coronary artery calcium score (CACS) for major adverse cardiovascular events (MACEs) in Bulgarian patients with chronic coronary syndrome. An observational study conducted in a cardiology department. This observational study included 214 patients. The study population was divided into three major groups according to their CACS level estimated with the Agatston calculating model: 0 (group I), 1-400 (group II), and >400 (group III) Agatston units (AU). The patients were followed-up for MACE development over a mean period of 3.8 years. The Cox proportional hazard regression analysis was performed. The MACE rate in patients with CACS = 0 was significantly higher in patients with low-density lipoprotein >3 mmol/L (hazard ratio [HR] 3.5; 95% confidence interval [CI] 1.87-6.64; P < 0.05) and with paroxysmal atrial fibrillation (HR 4.33; 95% CI 1.25-16.92; P < 0.05). In group II, the incidence of MACE was significantly elevated in patients with coronary calcium volume >75 Hounsfield units (HU) (HR 3.56; 95% CI 1.39-9.14; P < 0.05), calcium score of aortic valve >30 AU (HR 3.2; 95% CI 1.36-4.76; P < 0.05), and left ventricular mass over 125 g (HR 3.24; 95% CI 1.65-7.56; P < 0.05). Our data revealed that different factors in the risk profile of the three patient groups were associated with an increased rate of MACEs.

Delivery balloon volume positively correlates with the diameter and effective orifice area of implanted SAPIEN 3

BackgroundIn transcatheter aortic valve replacement (TAVR) using SAPIEN 3 (S3) (Edwards Lifesciences, Irvine, CA, USA), some clinicians decrease or increase the delivery balloon volume (VOL) when deploying S3 or conducting post-dilatation. However, the effects of controlling VOL on transcatheter heart valve diameter (THVD) and valve function remain unclear. We assessed associations among VOL, THVD, and effective orifice area (EOA) of S3. MethodsWe enrolled patients undergoing TAVR using 23- and 26-mm S3 in Sendai Kousei Hospital between 2017 and 2019. VOL was controlled based on preprocedural computed tomography and intraprocedural transesophageal echocardiography (TEE). THVD were defined as the diameters of transcatheter heart valve at mid-level measured by TEE. ResultsIn enrolled 332 patients (23-mm, n = 188; 26-mm, n = 144), one (0.3%) and two (0.6%) developed annulus rupture and moderate/severe paravalvular leak, respectively. VOL at deployment was positively correlated with THVD on deployment (23-mm, r = 0.44, p < 0.001; 26-mm, r = 0.57, p < 0.001) and EOA (23-mm, r = 0.23, p = 0.0019; 26-mm, r = 0.22, p = 0.0094). In multiple regression analyses, VOL and post-dilatation were significant determinants of THVD, although aortic annulus area, calcium volume, and pre-dilatation were not. The areas under the receiver operating characteristic curve that were used to evaluate the accuracy of the index obtained by dividing THVD by body surface area (indexed THVD) to predict patient–prosthesis mismatch (PPM) were 0.744 and 0.811 in the 23- and 26-mm cohorts, respectively. A cut-off indexed THVD of ≤11.5 and 12.1 mm/m2 well predicted PPM (23-mm, odds ratio, 5.20; 95% confidence interval, 1.33–20.3; 26-mm, odds ratio 14.1, 95% confidence interval 2.40–81.0). ConclusionVOL was positively correlated with THVD and EOA. Smaller indexed THVD was associated with a higher incidence of PPM. Controlling VOL under on-site THVD evaluation may be useful in reducing the PPM incidence.

How to use the aortic valve calcium score to improve the results of transcatheter aortic valve implantation with a self-expanding prosthesis

In recent years, transcatheter aortic valve implantation (TAVI) without predilation (direct TAVI) has become the preferred method for implanting TAVI prostheses. Appropriate patient selection is important to avoid suboptimal outcomes and associated complications. To evaluate whether aortic valve calcification measured with computed tomography predicts suboptimal results from direct TAVI with a self-expanding prosthesis. Single-centre retrospective analysis of patients who received a CoreValve™ prosthesis (Medtronic, Minneapolis, MN, USA) in a direct TAVI procedure between January 2018 and March 2019. Aortic valve calcification assessment (aortic valve calcium score, calcium volume and calcium mass) was calculated from the computed tomography scan before TAVI. Procedural characteristics, need for postdilation and complications were analysed. Of 168 included patients, 18 were postdilated. Aortic valve calcium score (4259 vs. 2578; P<0.001), calcium volume (1184 vs. 647mm3; P<0.001) and calcium mass (642 vs. 368mg; P<0.001) were higher in patients needing postdilation. Aortic valve calcium score (odds ratio 9.73; P=0.004), calcium volume (odds ratio 8.48; P=0.006) and calcium mass (odds ratio 6.21; P=0.006) were independent predictors of suboptimal direct TAVI outcomes. A high aortic valvular calcium score, assessed by computed tomography scan, is an independent predictor of suboptimal prosthesis implantation outcomes in direct TAVI.

Coronary Computed Tomography Angiography Analysis of Calcium Content to Identify Non-culprit Vulnerable Plaques in Patients With Acute Coronary Syndrome.

BackgroundAside from the culprit plaque, the presence of vulnerable plaques in patients with acute coronary syndrome (ACS) may be associated with future cardiac events. A link between calcification and plaque rupture has been previously described.AimTo assess whether analysis of the calcium component of coronary plaques using CT angiography, coronary computed tomographic angiography (CCTA) can help to detect additional vulnerable plaques in patients with non-ST elevation myocardial infarction (NSTEMI).Materials And MethodsCross sectional study of consecutive patients referred for NSTEMI from 30 July to 30 August 2018 with CCTA performed before coronary angiography with systematic optical coherence tomography (OCT) analysis of all coronary arteries within 24 h of clinical onset of NSTEMI. Three types of plaques were defined: culprit plaques defined by angiography (vulnerable culprit plaques–VCP) – plaques with a fibrous cap thickness < 65 microns or thrombus in OCT (vulnerable non-culprit plaque–VNCP) – plaques with a fibrous cap thickness ≥ 65 microns in OCT (stable plaque–SP).ResultsA total of 134 calcified plaques were identified in 29 patients (73% male, 59 ± 14 years) with 29(22%) VCP, 28(21%) VNCP and 77(57%) SP. Using CCTA analysis of the calcium component, factors associated with vulnerable plaques were longer calcification length, larger calcification volume, lower calcium mass, higher Agatston score plaque-specific (ASp), presence of spotty calcifications and an intimal position in the wall. In multivariate analysis, ASp, calcification length and spotty calcifications were independently associated to vulnerable plaques. There was no difference between VCP and VNCP.ConclusionsCCTA analysis of calcium component of the plaque could help to identify additional vulnerable plaques in NSTEMI patients.

Quantification of Coronary Calcification using High-Resolution Photon-Counting-Detector CT and an Image Domain Denoising Algorithm.

Coronary artery calcification (CAC) is an important indicator of coronary disease. Accurate volume quantification of coronary calcification, especially calcifications smaller than a few mm, using computed tomography (CT) is challenging due to calcium blooming, which is a consequence of limited spatial resolution. In this study, ex-vivo coronary specimens were scanned on a clinical photon-counting detector (PCD) CT scanner and the estimated coronary calcification volume were compared with a conventional energy-integrating detector (EID) CT. Scans were performed using the same tube potential and radiation dose (120 kV, 9.3 mGy CTDIvol). EID-CT images were reconstructed using our routine clinical protocol for CAC quantification. PCD-CT images were reconstructed using a sharper reconstruction kernel than that was supported by the EID-CT scanner, resulting in improved resolution but higher image noise levels. An image-based denoising algorithm was applied to the PCD-CT images to achieve similar noise levels as the EID-CT images. Calcifications were segmented to estimate the volume. Micro-CT images of the same calcifications were acquired and served as the reference standard. PCD-CT images showed reduced calcium blooming artifacts compared to EID-CT. Calcification volume estimates were found to overestimate the micro-CT volumes by 9 ± 12% for PCD-CT data, and 24 ± 18% for the EID-CT data. Volume quantification accuracy of the current PCD-CT system was also found to be superior to a previous-generation investigational PCD-CT scanner with larger detector pixels.

Comprehensive Assessment of Coronary Calcification in Intravascular OCT Using a Spatial-Temporal Encoder-Decoder Network.

Coronary calcification is a strong indicator of coronary artery disease and a key determinant of the outcome of percutaneous coronary intervention. We propose a fully automated method to segment and quantify coronary calcification in intravascular OCT (IVOCT) images based on convolutional neural networks (CNN). All possible calcified plaques were segmented from IVOCT pullbacks using a spatial-temporal encoder-decoder network by exploiting the 3D continuity information of the plaques, which were then screened and classified by a DenseNet network to reduce false positives. A novel data augmentation method based on the IVOCT image acquisition pattern was also proposed to improve the performance and robustness of the segmentation. Clinically relevant metrics including calcification area, depth, angle, thickness, volume, and stent-deployment calcification score, were automatically computed. 13844 IVOCT images with 2627 calcification slices from 45 clinical OCT pullbacks were collected and used to train and test the model. The proposed method performed significantly better than existing state-of-the-art 2D and 3D CNN methods. The data augmentation method improved the Dice similarity coefficient for calcification segmentation from 0.615±0.332 to 0.756±0.222, reaching human-level inter-observer agreement. Our proposed region-based classifier improved image-level calcification classification precision and F1-score from 0.725±0.071 and 0.791±0.041 to 0.964±0.002 and 0.883±0.008, respectively. Bland-Altman analysis showed close agreement between manual and automatic calcification measurements. Our proposed method is valuable for automated assessment of coronary calcification lesions and in-procedure planning of stent deployment.

Frequency, shape, and estimated volume of intracranial physiologic calcification in different age groups investigated by brain computed tomography scan: a retrospective study.

Intracranial calcification is referred to calcification of parenchyma and vascular structures in brain which can be physiologic or pathologic. This study was conducted with the purpose of investigating the frequency, location, pattern, dimensions and estimated volume of intracranial physiologic calcification (IPC) by computer tomography in different age groups. In this cross-sectional retrospective study, brain computed tomography scans of 216 patients were analyzed in 9 age groups each containing 24 patients from 2 to 89 years old. Data were analyzed by SPSS software using one way analysis of variance (ANOVA, post hoc Tukey), chi square, and linear regression tests (P≤0.05 was considered significant). Rate of calcification in different areas were as follows: pineal gland (75.0%), habenula (36.4%), pineohabenula (15.0%), right lateral ventricle choroid plexus (RCP) (67.7%), left lateral ventricle choroid plexus (LCP) (62.7%), falx cerebri (26.8%), petroclinoid ligament (13.2%), tentorium cerebelli (6.8%), third ventricle choroid plexus (0.9%), fourth ventricle choroid plexus (2.7%), basal ganglia (0.9%). A significant correlation exists between the presence of calcification in pineal, habenula, RCP, and LCP (P≤0.001). Nodular shape of calcification was dominant (47.9%). Estimated volume of pineal calcification showed increased levels in group 8 (70–79 years old) compared to group 2 (10–19 years old) (P≤0.05). Since the accurate description of radiologic appearance of IPCs (location, shape, and size) accompanied with age and clinical manifestation is of great importance in diagnosis and distinguishing from pathologic calcification—for example in patients with melatonin dysregulation or schizophrenic patients—this study was required.

Plasma amyloid-β40 in relation to subclinical atherosclerosis and cardiovascular disease: A population-based study

Background and aimsWe aimed to determine associations of plasma amyloid-β40 (Aβ40) with subclinical atherosclerosis and risk of atherosclerotic cardiovascular disease (ASCVD) in the general population. MethodsBetween 2002 and 2005, plasma Aβ40 was measured by single molecule array (SiMoA®) in 3879 participants of the population-based Rotterdam Study (mean age: 71 years, 61% female). Subclinical atherosclerosis was quantified as computed tomography-assessed calcification volumes. We determined the association of Aβ40 with calcification volumes and clinical ASCVD event risk, and repeated the analyses for ASCVD in a replication cohort of 1467 individuals. ResultsHigher levels of Aβ40 were associated with increased volumes of calcification in the coronary arteries and to a lesser extent extracranial carotid arteries, independent of traditional cardiovascular risk factors. Of all 3879 participants, 748 developed ASCVD during a median 9.7 years of follow-up. In age- and sex-adjusted models, higher Aβ40 predisposed to a minor increase in ASCVD risk (HR [95%CI]: 1.11[1.02–1.21] per 1-SD increase in Aβ40), driven by coronary heart disease (HR: 1.17[1.05–1.29]) rather than stroke (HR: 1.04[0.93–1.16]). However, excess risk of clinical outcomes was largely explained by baseline differences in cardiovascular risk factors and attenuated after further adjustment (for ASCVD– HR: 1.05[0.96–1.15] and for CHD– HR: 1.08[0.96–1.20]). Results were similar in the replication cohort, with highest risk estimates for CHD (HR: 1.24[1.04–1.48]) in age- and sex-adjusted models, attenuated after adjustment for cardiovascular risk factors (HR: 1.15[0.96–1.39]). ConclusionsIn this population-based study, higher plasma amyloid-β40 is associated with subclinical atherosclerosis, but not risk of first-ever ASCVD after accounting for traditional cardiovascular risk factors.

The Role of Inorganics in Preeclampsia Assessed by Multiscale Multimodal Characterization of Placentae.

Preeclampsia is one of the most dangerous diseases in pregnancy. Because of the hypertensive nature of preeclampsia, placental calcifications are believed to be a predictor for its occurrence, analogous to their role in cardiovascular diseases. However, the prevalence and the relevance of calcifications for the clinical outcome with respect to preeclampsia remains controversial. In addition, the role of other inorganic components present in the placental tissue in the development of preeclampsia has rarely been investigated. In this work, we therefore characterized inorganic constituents in placental tissue in groups of both normotensive and preeclamptic patients (N = 20 each) using a multi-scale and multi-modal approach. Examinations included elemental analysis (metallomics), sonography, computed tomography (CT), histology, scanning electron microscopy, X-ray fluorescence and energy dispersive X-ray spectroscopy. Our data show that tissue contents of several heavy metals (Al, Cd, Ni, Co, Mn, Pb, and As) were elevated whereas the Rb content was decreased in preeclamptic compared to normotensive placentae. However, the median mineral content (Ca, P, Mg, Na, K) was remarkably comparable between the two groups and CT showed lower calcified volumes and fewer crystalline deposits in preeclamptic placentae. Electron microscopy investigations revealed four distinct types of calcifications, all predominantly composed of calcium, phosphorus and oxygen with variable contents of magnesium in tissues of both maternal and fetal origin in both preeclamptic and normotensive placentae. In conclusion our study suggests that heavy metals, combined with other factors, can be associated with the development of preeclampsia, however, with no obvious correlation between calcifications and preeclampsia.

Risk of conduction disturbances following different transcatheter aortic valve prostheses: the role of aortic valve calcifications.

OBJECTIVESTo assess the impact of prosthesis choice and aortic valve calcifications on the occurrence of conduction disturbances after transcatheter aortic valve implantation (TAVI).METHODSWe retrospectively analyzed the preoperative clinical characteristics, electrocardiograms, contrast-enhanced multidetector computed tomography scans and procedural strategies of patients who underwent TAVI in our center between January 2012 and June 2017. Quantification of calcium volume was performed for each aortic cusp above (aortic valve) and below (left ventricular outflow tract, LVOT) the basal plane. Multivariate analysis was performed to evaluate risk factors for the onset of new bundle branch block (BBB), transient and permanent atrioventricular block (tAVB, pAVB).RESULTSA total of 569 patients were included in the study. Six different prostheses were implanted (Edwards Sapien XT, n = 162; Edwards Sapien 3, n = 240; Medtronic CoreValve, n = 27; Medtronic CoreValve Evolut R, n = 21; Symetis Acurate, n = 56; Symetis Acurate neo, n = 63). The logistic regression analysis for BBB showed association with baseline left anterior hemiblock. The logistic regression for tAVB, found the prior valvuloplasty and the balloon post-dilatation associated with the outcome. Baseline left and right BBB, degree of oversizing, and LVOT calcification beneath the non-coronary cusp were associated with pAVB. Neither the prosthesis model, nor the use of a self-expandable prosthesis showed statistical significance with the above-mentioned outcomes on univariate analysis. CONCLUSIONSLVOT calcification beneath the non-coronary cusp, baseline left anterior hemiblock, right BBB, balloon post-dilatation, prior valvuloplasty and oversizing are independently associated with postprocedural conduction disturbances after TAVI. Use of a self-expandable prosthesis may show a lower incidence of AVB, if applied in lower calcified aortic valves.

Influence of rivaroxaban compared to vitamin K antagonist treatment upon development of cardiovascular calcification in patients with atrial fibrillation and/or pulmonary embolism.

BackgroundVitamin K antagonists (VKA) such as warfarin or phenprocoumon have been the mainstay of therapy for long‐term oral anticoagulant therapy (OAT) in patients with atrial fibrillation or with pulmonary embolism. Due to interferences with matrix Gla‐protein, an important vitamin K‐dependent local calcification inhibitor in cardiovascular structures, VKA antagonists stimulate cardiovascular calcification (CVC). In contrast, rivaroxaban, a nonvitamin K‐dependent oral anticoagulant (NOAC), should be neutral in terms of CVC. We seek to investigate these potential differences in CVC development between VKA versus NOACs in a randomized controlled trial (RCT).MethodsThe influence of rivaroxaban compared to vitamin K antagonist treatment upon development of cardiovascular calcification in patients with atrial fibrillation and/or pulmonary embolism trial (NCT02066662) is a multicenter, prospective RCT with a two‐arm, open‐label study design. The primary endpoint is the progression of coronary and aortic valve calcification (quantified as calcification volume score) as assessed by cardiac computed tomography (CT) at 24 months in patients either treated by rivaroxaban or VKA. A total of 192 patients were randomized in a 1:1 fashion. The main inclusion criteria were the presence of atrial fibrillation and/or pulmonary embolism with the indication for OAT and pre‐existent coronary calcification. The development of CVC will be assessed by follow‐up CT at 12 and 24 months.ResultsIn total 192 patients (median age 70, 72% male) were enrolled over a period of 5 years and followed up for 2 years.

Automatic Measurement of Vascular Calcifications in Patients with Aorto-Iliac Occlusive Disease to Predict the Risk of Re-intervention After Endovascular Repair

There is currently a lack of consensus and tools to easily measure vascular calcification using computed tomography angiography (CTA). The aim of this study was to develop a fully automatic software to measure calcifications and to evaluate the interest as predictive factor in patients with aorto-iliac occlusive disease. This study retrospectively included 171 patients who had endovascular repair of an aorto-iliac occlusive lesion at the University Hospital of Nice between January 2011 and December 2019. Calcifications volumes were measured from CTA using an automatic method consisting in three sequential steps: image pre-processing, lumen segmentation using expert system, and deep learning algorithms and segmentation of calcifications. Calcification volumes were measured in the infrarenal abdominal aorta and the iliac arterial segments, corresponding to the common and the external iliac arteries. Among 171 patients included with a mean age of 65years, the revascularization was performed on the native external and internal iliac arteries in, respectively: 83 patients (48.5%), 107 (62.3%), and 7 (4.1%). The mean volumes of calcifications were 2,759mm3 in the infrarenal abdominal aorta, 1,821mm3 and 1,795mm3 in the right and left iliac arteries, respectively. For a mean follow-up of 39months, target lesion re-intervention was performed in 55 patients (32.2%). These patients had higher volume of calcifications in the right and left iliac arteries, compared with patients who did not have a re-intervention (2,274mm3 vs. 1,606mm3, P=0.0319 and 2,278 vs. 1,567mm3, P=0.0213). The development of a fully automatic software would be useful to facilitate the measurement of vascular calcifications and possibly better inform the prognosis of patients.

A Novel and Practical Protocol for Three-Dimensional Assessment of Alveolar Cleft Grafting Procedures.

To evaluate the reproducibility and accuracy of a new, easy-to-use volumetric assessment of the alveolar cleft. Twelve cone-beam computed tomography (CBCT) datasets of patients with a unilateral cleft lip, alveolus, and palate were evaluated by two investigators. Residual alveolar cleft calcified volume one year after surgery was analyzed by using standardized landmarks to determine the borders of the cleft defect and semi-automatically segment the alveolar cleft defect. The Dice-coefficient between observers for the segmented preoperative alveolar cleft defect was 0.81. Average percentage of residual alveolar cleft calcified material was 66.7% one year postoperatively. This study demonstrates a reliable and practical semi-automatic three-dimensional volumetric assessment method for unilateral clefts using CBCT.