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IntroductionThe latest guidelines from the European Society of Cardiology on the management of valvular heart disease have recommended the use of calcium scoring of the aortic valve (AoV) on computed tomography (CT) in patients with severe aortic stenosis (AS) on echocardiography (Baumgartner, Falk, et al., 2017). The objective of this study was to calculate the AoV calcification in patients with severe AS on echocardiography.MethodsData was prospectively collected on all patients undergoing CT for consideration of transcatheter aortic valve implantation (TAVI) from July 2019 - January 2020. CT was performed on multidetector scanners, (Siemens SOMATOM AS+ and Canon Aquilion ONE) and measurements of AoV calcification and AoV area were performed using validated software (TeraRecon, California). Severe AS was defined as an aortic valve area of <1 cm2 on echocardiography. Pearson correlation analysis was performed using R v3.3.3.ResultsThe cohort consisted of 81 patients, 18 of whom contemporaneous echocardiography was available. There were a range of AoV calcium scores from 373–5478, with a mean score of 2,832 arbitrary units. There was a very weak negative correlation between the AoV area and the AoV calcification r=-.06, p=0.42 (Pearson’s). This relationship was not statistically significant.ConclusionIn patients with severe aortic stenosis on echocardiography, there is no correlation between AoV calcification and AoV area. It is important to understand the relationship between AoV calcification and AoV area before its use in clinical practice can be advocated.

Vascular calcification (VC), a pathophysiological consequence of atherosclerosis and arteriosclerosis, is associated with an inevitably stiffened arterial system, leading to development of cardiovascular diseases. Currently, there are no effective strategies for treating vascular calcification. Caloric restriction (CR) is a dietary intervention that involves reduction of total calories below ad libitum intake without nutritional insufficiency or malnutrition. Over the past decade the potential for CR to delay the onset of age-related chronic diseases and offer direct cardioprotective effects have become well recognised. However, the effect of CR on VC has yet to be examined.We isolated VSMCs form the aortae of CR mice and cultured them under calcifying conditions (3mM Pi) ex vivo. VSMCs derived from CR mice showed reduced calcification compared to VSMCs from mice fed ad libitum (p<0.0001). To test this in vitro we starved rat valve interstitital cells for 48hrs (RVICs) and primary vascular smooth muscle cells (VSMCs) for 96hrs by culturing them in HBSS along with treating them with high dosage of calcium (Ca) and phosphate (Pi) (2.7mM Ca/2.5mM Pi for RVICs and 3mM Pi for VSMCs). The starved RVICs and VSMCs show reduced calcification compared to the cells grown in normal calcifying media enriched with serum and glucose (p<0.0001). These starved cells show reduced expression of key calcifying marker Runx2 (3 fold decrease, p<0.0005) and PHOSPHO1 and a concomitant increase in the calcification inhibitor ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1, 3 fold increase, p<0.0006).To investigate the molecular mechanism underpinning starvation-induced abrogation of VC, we carried out stable isotope labeling by/with amino acids in cell culture (SILAC) based quantitative proteomics comparison between calcified and starved RVICS. The majority of proteins showing >2 fold upregulation were from the ubiquitin proteasome system (UPS). UPS is a selective proteolytic system in which substrates are recognised and tagged with ubiquitin for processive degradation by the proteasome. Treatment of both RVICs and VSMCs with MG132 (UPS inhibitor; 10uM) cultured under calcifying conditions accelerated calcification in both cell types(p<0.0001). Together these data suggest that CR protects against VC by degrading crucuial regulators of calcification including PHOSPHO1 and Runx2.This novel finding could lead to the application of CR-mimetics to combat vascular calcification.

Medial vascular calcification has emerged as a putative key factor contributing to the excessive cardiovascular mortality of patients with chronic kidney disease (CKD). Hyperphosphatemia is considered a decisive determinant of vascular calcification in CKD. A critical role in initiation and progression of vascular calcification during elevated phosphate conditions is attributed to vascular smooth muscle cells (VSMCs), which are able to change their phenotype into osteo-/chondroblasts-like cells. These transdifferentiated VSMCs actively promote calcification in the medial layer of the arteries by producing a local pro-calcifying environment as well as nidus sites for precipitation of calcium and phosphate and growth of calcium phosphate crystals. Elevated extracellular phosphate induces osteo-/chondrogenic transdifferentiation of VSMCs through complex intracellular signaling pathways, which are still incompletely understood. The present review addresses critical intracellular pathways controlling osteo-/chondrogenic transdifferentiation of VSMCs and, thus, vascular calcification during hyperphosphatemia. Elucidating these pathways holds a significant promise to open novel therapeutic opportunities counteracting the progression of vascular calcification in CKD.

Provision of non-invasive vascular imaging results to individuals has been shown to improve cardiovascular disease risk factor control: its impact on diet remains uncertain. In this two-arm, single-blind, parallel, 12-week randomized controlled trial, 240 participants, 57.5% females aged 60–80 y had abdominal aortic calcification and clinical assessments performed at a hospital clinic. Participants were randomized 1:1 to receive (intervention n  = 121) or not (control n  = 119) their calcification results. Both groups received educational resources on cardiovascular disease risk control and were unblinded to the intervention. Outcome measures were performed at baseline and 12 weeks. The primary outcomes of the study were changes in fruit and vegetable intake measures over 12 weeks assessed using plasma carotenoid concentrations (biomarkers of FV intake) and a food frequency questionnaire. Secondary outcomes included 12-week changes in other aspects of the diet, physical activity, body weight, blood pressure, heart rate, lipid profile, glucose concentrations, estimated cardiovascular disease risk score, and medication use. Between-group differences were tested using linear mixed-effects regression. There were no between-group differences in the primary outcomes at 12 weeks: plasma carotenoids (mean difference +0.03 µg/mL [95%CI −0.06, 0.13]) and fruit and vegetable intakes (+18 g/d [−37, 72]). However, the provision of calcification results led to between-group differences in serum total (−0.22 mmol/L [−0.41, −0.04]) and non-HDL (−0.19 mmol/L [−0.35, −0.03]) cholesterol, and estimated cardiovascular disease risk score (−0.24% [−0.47, −0.02]). No between-group differences were seen for other secondary outcomes. In this work, providing vascular imaging results did not improve diet but did improve some cardiovascular disease risk factors (Australian and New Zealand Clinical Trials Registry ACTRN12618001087246). It is unclear whether providing the results of abdominal aortic calcification imaging to patients improves diet parameters. This randomized trial shows that this intervention does not lead to improvements in fruit and vegetable intake, while showing an effect on some cardiovascular disease risk factors used as secondary outcomes.

We describe the case of an 84-year-old woman, hospitalized for acute heart failure, presenting with an intracardiac mass detected on echocardiography. The differential diagnosis and the usefulness of multimodality imaging are discussed.

Background Arteriosclerosis is prevalent in patients with chronic kidney disease (CKD). Our aims were to investigate (1) the effects of 12 months of either balance- or strength- both in combination with endurance training on abdominal aortic calcification (AAC); on some lipids and calcific- and inflammatory markers; and (2) the relationships between the change in AAC score and these markers in non-dialysis dependent patients with CKD stages 3 to 5. Methods One hundred twelve patients (mean age 67 ± 13 years), who completed 12 months of exercise training; comprising either balance- or strength training, both in combination with endurance training; with a measured glomerular filtration rate (mGFR) 22.6 ± 8 mL/min/1.73m 2 , were included in this study. AAC was evaluated with lateral lumbar X-ray using the scoring system described by Kauppila. Plasma fetuin-A, fibroblast growth factor 23 (FGF23) and interleukin 6 (IL6) were measured with Enzyme-linked immunosorbent assay (ELISA) kits. Results After 12 months of exercise training, the AAC score increased significantly in both groups; mGFR and lipoprotein (a) decreased significantly in both groups; parathyroid hormone (PTH) and 1,25(OH) 2 D 3 increased significantly only in the strength group; fetuin-A increased significantly only in the balance group. Plasma triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, FGF23, phosphate, calcium, IL6, C-reactive protein (CRP), albumin were unchanged. The increase in AAC score was positively related to ageing and the levels of baseline triglycerides and lipoprotein (a). Conclusions Exercise training did not prevent the progression of AAC; it might have contributed to the reduced levels of lipoprotein (a) and unchanged levels of calcific- and inflammatory markers in these patients with non-dialysis dependent CKD. Hypertriglyceridemia, high levels of lipoprotein (a) and ageing emerged as longitudinal predictors of vascular calcification in these patients. Trial registration NCT02041156 at www.ClinicalTrials.gov. Date of registration: January 20, 2014. Retrospectively registered.

Abdominal aortic calcification (AAC) detected on lateral vertebral fracture assessment is associated with increased cardiovascular risk. Vitamin D deficiency and toxicity have been linked with vascular calcification. The objective of this study was to determine the effect of high-dose vitamin D on the progression of AAC. The Physical Performance, Osteoporosis and vitamin D in African American Women (PODA) is a randomized, clinical trial examining the effect of vitamin D. There were 14.7% subjects with AAC in the vitamin D group, compared to 12.1% in the placebo group at baseline. The prevalence of extended AAC at baseline was 6.4% in the vitamin D group and 3.5% in the placebo group. The extended calcification scores over time were not different between groups. There was no association between AAC and serum 25(OH)D. However, PTH was associated with an increase in AAC in the placebo group.

PurposeVascular calcification (VC) is an independent risk factor for cardiovascular disease in hemodialysis patients while Matrix GLA protein (MGP) is one of the most potent inhibitors of VC and its activation is vitamin K dependent. The aim of this study is to investigate the role of oral vitamin K2 supplementation in the prevention of VC progression in haemodialysis patients.MethodsWe conducted a prospective randomized interventional study in patients on hemodialysis. Patients were randomly assigned to either receiving orally 200 μgr of vitamin K2 (vitamin K2/MK-7, Solgar) every day for 1 year or no treatment. Uncarboxylated MGP (uc-MGP) concentrations were quantified using ELISA at randomization, at 3 and at 12 months. Aortic calcification was evaluated using Agatston score after an abdominal computed tomography scan that was performed at the beginning and at 12 months of follow-up.ResultsThere were 102 patients that were randomized. After 1 year of follow-up, 22 patients from the vitamin K2 group and 30 patients from the control group were included in the analysis. After 3 months of treatment, uc-MGP values remained unchanged in the vitK2 group but after 1 year were reduced by 47% (p = 0.005). Furthermore, uc-MGP at 1 year was increased by 12% in the control group. At 1 year, vitK2 group had significantly lower values of uc-MGP in comparison to controls (p = 0.03). Agatston score was increased significantly both in vitamin K2 and control group at 1 year with no difference between groups.ConclusionsOral administration of vitamin K2 in patients on haemodialysis reduced serum uc-MGP levels but did not have an effect in the progression of aortic calcification.

Coronary artery calcification is common among patients undergoing percutaneous coronary intervention (PCI), and severe coronary artery lesion calcification is associated with increased procedural complexity, stent under-expansion, and high rates of intraprocedural complications and out-of-hospital adverse events. Whether calcium ablation before stent implantation can mitigate these adverse events is not currently established. We aimed to prospectively compare orbital atherectomy with a balloon angioplasty-based strategy before stent implantation for the treatment of severely calcified coronary lesions. In this multicentre, open-label, randomised controlled trial conducted at 104 medical centres in the USA, patients (aged ≥18 years) with severely calcified coronary lesions were randomly assigned (1:1) to orbital atherectomy or balloon angioplasty before PCI with drug-eluting stents using a web-based system (block sizes of four and six) and stratified by intended treatment of single versus multiple lesions and enrolling site. Randomly assigned lesions were deemed by operators to be eligible for both treatment strategies. Operators and patients were not masked to treatment. The two powered coprimary study endpoints were target vessel failure at 1 year (a composite of cardiac death, target vessel myocardial infarction, or ischaemia-driven target vessel revascularisation) and post-procedural minimal stent area at the site of maximal calcification, as assessed by intravascular optical coherence tomography in an imaging patient cohort. Primary analyses were by intention-to-treat. The trial is registered at ClinicalTrials.govNCT03108456, and 2-year follow-up is ongoing. From March 27, 2017, to April 13, 2023, 2005 patients with 2492 lesions were randomly assigned to lesion preparation with orbital atherectomy (1008 patients with 1250 lesions) or balloon angioplasty (997 with 1242 lesions) before stent implantation. Median patient age was 70·0 years (IQR 64·0–76·0). 541 (27·0%) of 2005 patients were female and 1464 (73·0%) were male. Angiographically severe calcium was confirmed by the core laboratory in 1088 (97·1%) of 1120 lesions assigned to orbital atherectomy and 1068 (97·0%) of 1101 lesions assigned to balloon angioplasty. PCI was guided by intravascular imaging in 627 (62·2%) of 1008 patients in the orbital atherectomy group and 619 (62·1%) of 997 in the balloon angioplasty group. Target vessel failure events within 1 year occurred in 113 of 1008 patients in the orbital atherectomy group (1-year target vessel failure 11·5% [95% CI 9·7 to 13·7]) and in 97 of 997 patients in the balloon angioplasty group (10·0% [8·3 to 12·1]; absolute difference 1·5% [96% CI –1·4 to 4·4]; hazard ratio 1·16 [96% CI 0·87 to 1·54], p=0·28). Among those in the optical coherence tomography substudy cohort (276 patients with 286 lesions in the orbital atherectomy group and 279 patients with 292 lesions in the balloon angioplasty group), the mean minimal stent area at the site of maximal calcification was 7·67 mm2 (SD 2·27) in the orbital atherectomy group and 7·42 mm2 (2·54) in the balloon angioplasty group (mean difference 0·26 [99% CI –0·31 to 0·82]; p=0·078). Cardiac death events within 1 year occurred in 39 of 1008 patients in the orbital atherectomy group and in 26 of 997 in the balloon angioplasty group. Routine treatment with orbital atherectomy before drug-eluting stent implantation did not increase minimal stent area or reduce the rate of target vessel failure at 1 year compared with a balloon angioplasty-based approach in severely calcified lesions deemed eligible for both treatment strategies. These data support a balloon-first approach for most calcified coronary artery lesions that can be crossed and dilated before stent implantation, guided by intravascular imaging. Abbott Vascular (Abbott).

Vascular calcification (VC), which is categorized by intimal and medial calcification, depending on the site(s) involved within the vessel, is closely related to cardiovascular disease. Specifically, medial calcification is prevalent in certain medical situations, including chronic kidney disease and diabetes. The past few decades have seen extensive research into VC, revealing that the mechanism of VC is not merely a consequence of a high-phosphorous and -calcium milieu, but also occurs via delicate and well-organized biologic processes, including an imbalance between osteochondrogenic signaling and anticalcific events. In addition to traditionally established osteogenic signaling, dysfunctional calcium homeostasis is prerequisite in the development of VC. Moreover, loss of defensive mechanisms, by microorganelle dysfunction, including hyper-fragmented mitochondria, mitochondrial oxidative stress, defective autophagy or mitophagy, and endoplasmic reticulum (ER) stress, may all contribute to VC. To facilitate the understanding of vascular calcification, across any number of bioscientific disciplines, we provide this review of a detailed updated molecular mechanism of VC. This encompasses a vascular smooth muscle phenotypic of osteogenic differentiation, and multiple signaling pathways of VC induction, including the roles of inflammation and cellular microorganelle genesis.