Heart Valve Calcification Research Articles

Numerical assessment of the effect of xenopericardial bioprosthetic heart valve calcifications on its biomechanics

Objective: to conduct a pilot study of the effect of bioprosthetic heart valve leaflet calcification on biomechanics and to identify the «stress in the material – dysfunction» relationship. Materials and methods. The study’s focus was on two commercially available UniLine bioprosthetic mitral valves sized 26 and 30 (NeoCor, Russia). The samples were subjected to microcomputer tomographic scanning in order to reconstruct calcium volumes. The resulting 3D models were correlated with prostheses of corresponding sizes and projected to the volume of the locking element in the Abaqus/CAE engineering analysis software (Dassault Systemes, France).Results. According to numerical modeling, the maximum principal stresses increased significantly to 90.8 MPa in the samples, the opening decreased qualitatively, and impact on the prosthetic frame increased. Comparison of stress diagrams of numerical simulation with samples demonstrates the relationship between peak amplitude and rupture and thinning localizations in the flap apparatus.Conclusion. The work presented demonstrated the findings of a pilot study of the connection between biomechanics in a patient-specific calcified mitral prosthetic heart valve UniLine and macroscopic characterization of explanted samples. The comparative stage showed that stress values correlate with localization of leaflet dysfunction.

#1624 The association between serum beclin 1 level and the presence of aortic valve calcification among individuals on hemodialysis

Abstract Background and Aims The autophagy pathway, a crucial regulator of cellular health and metabolism, plays a fundamental role in maintaining healthy blood vessel function. Studies have established its critical involvement in endothelial cell stability, vascular smooth muscle cell (VSMC) phenotype control, and VSMC calcium balance. Recent evidence, further, underlines autophagy's direct protective role against vascular calcification. It has been shown that autophagy can modulate different cardiovascular pathologies, including valvular calcification. We aimed to explore the potential link between the protein beclin 1 and heart valve calcification in dialysis patients. Method We compared two groups of 51 haemodialysis patients each, defined by the presence (Group 1) or absence of valve calcification (Group 2) on echocardiograms. Both groups underwent beclin 1 level measurements and other assessments (lipid profile). Cardiac valve calcification was diagnosed through echocardiography by identifying dense echoes exceeding 1 millimeter in thickness on one or more aortic valve cusps. The severity of calcification was then classified into three stages: Mild: Calcification thickness ranged from 1 to 3 millimeters and involved less than 50% of the valve leaflet. Moderate: Calcification thickness exceeded 3 millimeters but still affected less than half of the valve leaflet. Severe: Calcification thickness surpassed 3 millimeters and encompassed more than 50% of the valve leaflet. Results Our analysis demonstrated a statistically significant increase in beclin 1 levels in Group 2 compared to Group 1 (p<0.001), a striking relationship between lower beclin 1 levels and more severe valve calcification. Interestingly, a specific beclin 1 cutoff below 35.5 ng/ml offered the highest accuracy (98% sensitivity and 92% specificity) in predicting valve calcification. Notably, significant differences were found in lipid profiles (Analysis of the lipid profile revealed a striking trend in Group I, with significant elevations in cholesterol, triglycerides, and LDL. Conversely, HDL levels were significantly higher in Group II). and prevalence of heart disease between the groups. Analysis of IHD prevalence across the two groups yielded a striking result. Group 1 displayed a significantly higher proportion of individuals with IHD (17 cases) compared to group 2 (3 cases), with a statistically significant difference (p<0.001). Conclusion Based on these results, it appears promising to integrate serum Beclin 1 measurements into a risk assessment model for the development of heart valve calcification in dialysis patients.

Association of Matrix Metalloproteinase-2 (MMP-2) and MMP-9 Promoter Variants, Their Serum Levels, and Activities with Aortic Valve Calcification (AVC) in a Population from Western Iran.

Background: Matrix metalloproteinase (MMP) enzyme gene polymorphisms MMP-2-1575G/A and MMP-9-1562C/T promoter polymorphism, their serum levels, and activity are associated with aortic valve calcification (AVC). Materials and Methods: The synergistic link between the risk of AVC and the alleles T and A of MMP-9 and MMP-2 was investigated, respectively. Ninety-two cases with AVC and 92 healthy individuals from the west of Iran were included, and MMP- 2-1575G/A and MMP-9-1562C/T promoter polymorphisms were detected using PCR-RFLP. The serum levels and activity of MMP-2 and -9 were assessed using ELISA and gelatin zymography methods, respectively. In addition, serum biochemical markers, including FBS, urea and creatinine, cholesterol, triglyceride, HDL, LDL, calcium, phosphorus, and blood pressure: systolic blood pressure and diastolic blood pressure were measured. Results: Heart valve calcification disease was associated with a comparatively higher frequency of the A allele of the MMP2-1575 variation (p = 0.002). In addition, the frequency of T allele of the MMP9-1562 variant was higher than the control group (p = 0.007). Conclusion: MMP-2 and MMP-9 serum levels and activities were observed to be considerably higher in the experimental group than in the control group (p < 0.001). Patients are more susceptible to cardiovascular disease than the control group due to elevated serum levels and activity of MMP-2 and MMP-9.

BIOLOGICAL PROSTHESES FOR CARDIOVASCULAR SURGERY – A HALF-CENTURY HISTORY AND DEVELOPMENT PROSPECTS

HighlightsSurgical correction of cardiovascular deformities is inextricably linked with the use of prostheses. The development and clinical testing of biological prostheses has been conducted under the guidance of the Member of Russian Academy of Sciences Leonid Barbarash at the Kuzbass Cardiology Center for more than 50 years. The uniqueness of the developed products lies in the use of a new biological tissue preservative – ethylene glycol diglycidyl ether, and an integrated approach involving the development and manufacture of products, study of long-term replacement outcome, causes of prosthetic dysfunction and genetic aspects of the use of bioprostheses in patients. AbstractThis article highlights the main achievements in the development of biological prostheses for cardiovascular surgery under the leadership of the Member of Russian Academy of Sciences L.S. Barbarash since the 1980s. Throughout this period, Leonid Barbarash and his team have developed and mass-produced various designs of bioprosthetic heart valves and tissue preservation methods, arterial grafts, and patches. The article presents the results of developing next-generation vascular biodegradable grafts capable of complete remodeling and stimulating endothelialization after the implantation into the vascular bed. Moreover, we conducted a series of genetic studies evaluating the significance of gene polymorphisms of various pathogenetic pathways involved in the pathological calcification of native heart valves and their prostheses.

The Association Between Heart Valve Calcification and Long-term Clinical Outcomes in Patients With Peripheral Arterial Disease Undergoing Percutaneous Transluminal Angioplasty

The Association Between Heart Valve Calcification and Long-term Clinical Outcomes in Patients With Peripheral Arterial Disease Undergoing Percutaneous Transluminal Angioplasty

Multicentre, open-label, randomised, controlled trial to compare early intervention with calcimimetics and conventional therapy in preventing coronary artery calcification in patients with secondary hyperparathyroidism (UPCOMING): a study protocol

IntroductionCoronary artery and heart valve calcification is a risk factor for cardiovascular death in haemodialysis patients, so calcification prevention should be started as early as possible. Treatment with concomitant calcimimetics...

#6030 CARDIAC ULTRASOUND ASSESSMENT AND THE NOVEL INFLAMMATION, FIBROSIS AND CALCIFICATION BIOMARKERS IN ESKD PATIENTS ON HD THERAPY: A PILOT STUDY

Abstract Background and Aims Novel biomarkers for inflammation, fibrosis, and vascular calcification have been recently used for further assessment of cardiovascular risk. The aim of our prospective study is to assess the relation between the novel cardiovascular biomarkers and biomarkers for vascular calcification with cardiac ultrasound function/morphology alteration in high cardiovascular risk patients with end stage kidney disease (ESKD) on haemodialysis (HD) therapy. Baseline findings are discussed in this pilot paper Method The study included 58 ESKD patients [55% men, mean age of 60.3 ± 11.7 years, and median hemodialysis therapy duration of 6.2 years (1.2 -25.7)], treated with HD (3 sessions of 4 hours /week with high flux dialyzers). Personal and laboratory data have been retrieved from the patients HD files. Cardiac ultrasound assessment was performed during the second HD session of the week, after 2 hours of HD therapy. Blood samples have been taken before the same HD session in order to determine FGF 23, BMP 2, IL 1 beta, Galectin 3 and soluble ST 2 levels. All patients signed an informed consent for the study participation and the use of personal and laboratory data for scientific purposes. The study was approved by the medical ethics committee of the “Victor Babes” University of medicine and pharmacy and of the ethics committee of the HD center. Results On cardiac ultrasound assessment the patients presented aorta atheroma in 74.1%, aorta valve fibrosis in 74.1%, mitral valve fibrosis in 74.1% of the cases. Calcifications have been evidenced at aorta valve level in 58.6%, mitral valve level in 75.8% and endomyocardial level in 67.2% of the cases. Increased left ventricular mass was present in 82.7%, enlarged interventricular septum in 74.1% of the cases. Decreased left ventricle diastolic filing (Appleton pattern - E/A) was evidenced in 55,1% of the cases and decreased left ventricular ejection fraction in 37.9%. Right ventricle enlargement was detected in 24.1% of the patients. At baseline, FGF 23 was inversely corelated with HD therapy duration (p = 0.01), ESA dose (p = 0.016), and directly with galectin 3 levels (p &amp;lt; 0.05) but not with the ultrasound findings. BMP 2 levels corelated directly with serum albumin levels and inversely with left ventricle diastolic filing (E/A) (p &amp;lt; 0.05). IL1 levels were inversely corelated with iPTH (p = 0.046), calcium (p = 0.046 and phosphate (p = 0.030) levels but not ultrasound findings, Galectin 3 inversely corelated with cu Hb (p = 0.002), Urea (p = 0.036) and K levels (p = 0.001) and directly with bicarbonate (p = 0.035), FGF 23 (p &amp;lt; 0.05) and CRP levels (p&amp;lt;0.0001), ST2 inversely corelated with ESA dose (p = 0.009) and decreased left ventricle diastolic filing (E/A) (p &amp;lt; 0.05). At one year follow-up 12% of the patients died and mortality was significantly influenced by inter ventricle sept and right ventricle enlargement. Conclusion At baseline, though the investigated ESKD patients on HD therapy presented extensive cardiac valve fibrosis and heart valve and endomyocardial calcifications the investigated biomarker changes were not significantly supporting the ultrasound findings. One- and two-years follow-up results may reveal the utility of biomarker assessment for cardiovascular outcomes in HD treated ESKD patients.

Clinical and Experimental Study of High Mobility Group Box-2 and Valvular Calcification in Elderly Patients with Degenerative Heart Valve Disease

Introduction: The aim of this study was to investigate the relationship between the high mobility group box-2 (HMGB2) and valve calcification in senile degenerative heart valve disease (SDHVD). Methods: According to the echocardiographic results, patients with calcified heart valves were used as the experimental group and patients without calcified heart valves were used as the control group; blood was drawn for testing, and serum levels of HMGB2 were measured by an enzyme-linked immunosorbent assay. Human heart valve interstitial cells (hVICs) cultured in vitro were randomly divided into two groups. The calcification group was cultured with a medium containing calcification induction solution and cells were induced on days 1, 3, and 5, and the control group was cultured with a standard medium. Expression of bone morphogenetic protein 4 (BMP-4) and HMGB2 in both groups was detected by Western blot. RT-PCR was performed to detect the expression of the HMGB2 gene during calcification. The hVICs were cultured in vitro for 4 days with different concentrations of exogenous HMGB2 (0.01 μg/mL, 0.1 μg/mL, 1 μg/mL, 2 μg/mL), while the control group was cultured with a standard medium and the expression of BMP-4 and NF-κB P65 was detected by Western blot. Results: The serum level of HMGB2 was 7.90 (5.92, 12.39) μg/L, higher than that of 7.06 (5.06, 9.73) μg/L in the valve calcification group in elderly patients with degenerative valve disease (p = 0.005); the differences were statistically significant. In in vitro experiments, the cellular calcification protein BMP-4 and the HMGB2 protein were higher in the calcification group compared to the control group (p < 0.05). Exogenous stimulation of hVICs with HMGB2 was able to upregulate the expression of BMP-4 and NF-κB P65 (p < 0.05). Conclusions: HMGB2 is correlated with valvular calcification in senile degenerative heart valve disease. The HMGB2 protein may promote the process of SDHVD valve calcification by activating the NF-κB pathway and upregulating the expression of BMP-4.

Risk factors and survival analysis of haemodialysis complicated with infective endocarditis.

The clinical features and risk factors for survival time were analysed in haemodialysis patients complicated with infective endocarditis. A total of 101 infective endocarditis (IE) patients treated at Hangzhou First People's Hospital, from January 1, 2012, to April 1, 2022, were included in the present study. Baseline demographic data and laboratory data were collected for statistical analysis of risk factors and survival time in the IE with haemodialysis group (HD-IE group, n=15) and the IE without haemodialysis group (NHD-IE group, n=86). Haemoglobin, red blood cells, C-reactive protein, procalcitonin, serum albumin, diabetes, invasive procedures, positive blood bacteria culture, heart valve calcification ratio, and left ventricular ejection fraction level were risk factors for infective endocarditis complicated with haemodialysis (P<0.05). Compared with the NHD-IE group, the HD-IE group had an obviously increased risk of mortality (χ2=6.323, P=0.012). The univariate Cox regression analysis showed that age, haemoglobin, red blood cells, serum albumin, left ventricular ejection score, longest vegetation diameter, combined hypotension and diabetes were risk factors for death; furthermore, multivariate Cox regression showed that age (HR=1.187, P=0.015), combined hypotension (HR=0.921, P=0.025) and the longest vegetation diameter (HR=9.191, P=0.004) were independent risk factors affecting the survival of patients. Collectively, the present study revealed that the mortality rate of HD-IE patients was higher than that of NHD-IE patients. Older age, hypotension, and the longest vegetation diameter were independent risk factors affecting the survival of patients. For HD-IE patients, active and effective antibiotic treatment or surgical treatment should be strongly recommended.

Trends in mortality and comorbidities in hemodialysis patients between 2012 and 2017 in an East-European Country: a retrospective study.

The aim of this study was to evidence trends and changes in mortality, comorbid conditions, prognosis, and causes of death after 5years of continuous evolution of hemodialysis (HD) patients in Romania. We included two cohorts of stable HD patients (901 from 2012 and 1396 from 2017). Both cohorts were followed up for 1year. The 5-year survivors of the 2012 cohort were identified in 2017 and their data changes were assessed. The 2017 patients were older, with longer time on dialysis, higher serum creatinine and urea levels, and required higher ultrafiltration volume per dialysis. They also had lower hemoglobin, lower C-reactive protein, higher albumin, higher calcium bicarbonate, and higher parathyroidectomy prevalence. The 2017 cohort presented with lower average dialysis flow, less administration of iron sucrose, had more catheters, lower hepatitis C prevalence, higher diabetes mellitus prevalence, higher heart valve calcifications, higher heart rate disorders, higher prevalence of left ventricular hypertrophy, and lower ejection fraction. Cardiovascular disease was the main cause of death in both years (50% in 2012 and 45.6% in 2017), followed by sepsis and cancer. The mortality was higher in 2017 compared to 2012 (14.1 vs 6.6%). The 5-year mortality was 37.2% with an average of 7.44%/year. The risk of death increased with age, higher C-reactive protein, higher phosphate, lower hemoglobin, and lower albumin. Cardiovascular disease remains the main causes of death in HD-treated patients but with decreasing trend. Developing regional therapeutic strategies for quality care with early intervention will most likely improve mortality.

Parathyroidectomy versus oral cinacalcet on cardiovascular parameters in peritoneal dialysis patients with advanced secondary hyperparathyroidism (PROCEED): A randomized trial.

This trial aimed to evaluate oral cinacalcet versus total parathyroidectomy with forearm autografting (PTx) on cardiovascular surrogate outcomes and health-related quality of life (HRQOL) measures in dialysis patients with advanced SHPT. In this pilot prospective randomized trial conducted in two university-affiliated hospitals, 65 adult peritoneal dialysis patients with advanced SHPT were randomized to receive either oral cinacalcet or PTx. Primary endpoints were changes in left ventricular (LV) mass index by cardiac magnetic resonance imaging and coronary artery calcium scores (CACS) over 12 months. Secondary endpoints included changes in heart valves calcium scores, aortic stiffness, biochemical parameters of chronic kidney disease-mineral bone disease (CKD-MBD) and HRQOL measures over 12 months. Changes in LV mass index, CACS, heart valves calcium score, aortic pulse wave velocity and HRQOL did not differ between-groups or within-groups, despite significant reductions in plasma calcium, phosphorus and intact parathyroid hormone in both groups. Cinacalcet-treated patients experienced more cardiovascular-related hospitalizations than those who underwent PTx (P=0.008) but the difference became insignificant after adjusting for baseline difference in heart failure (P=0.43). With the same monitoring frequency, cinacalcet-treated patients had fewer hospitalizations due to hypercalcemia (1.8%) than patients who underwent PTx (16.7%) (P=0.005). No significant changes were observed in HRQOL measures in either group. Both cinacalcet and PTx effectively improved various biochemical abnormalities of CKD-MBD and stabilized but did not reduce LV mass, coronary artery and heart valves calcification, arterial stiffness or improve patient-centered HRQOL measures in PD patients with advanced SHPT. Cinacalcet may be used in place of PTx for treating advanced SHPT. Long-term and powered studies are required to evaluate PTx versus cinacalcet on hard cardiovascular outcomes in dialysis patients.

Growth hormone-releasing hormone agonist attenuates vascular calcification in diabetic db/db mice.

Vascular calcification (VC) is an independent risk factor for cardiovascular diseases. VC increases mortality of all-causes. VC is one of most common cardiovascular complications in type II diabetes. So far, no therapy has been proven to be effective in treatment of clinical VC. The present study investigated the therapeutic effects of MR409, an agonistic analog of growth hormone-releasing hormone (GHRH-A), on VC in diabetic db/db mice. Diabetic mice were injected with MR409 subcutaneously every day for 8 weeks. Long-term treatment with MR409 improved serum lipid profile and endothelium-dependent relaxation to acetylcholine, and reduced vascular structural injury in diabetic mice without affecting serum growth hormone level. Echocardiography showed that calcium plaques present in heart valve of diabetic mice disappeared in diabetic mice after treatment with MR409. MR409 inhibited vascular calcium deposition associated with a marked reduction in the expressions of osteogenic-regulated alkaline phosphatase (ALP) and transcription osteogenic marker gene Runx2 in diabetic mice. MR409 also inhibited vascular reactive oxygen species (ROS) generation and upregulated the expressions of anti-calcifying protein Klotho in diabetic mice. Our results demonstrate that GHRH-A MR409 can effectively attenuate VC and heart valve calcification, and protect against endothelial dysfunction and vascular injury in diabetic mice without significantly affecting pituitary-growth hormone axis. The mechanisms may involve upregulation of anti-calcifying protein Klotho and reduction in vascular ROS and the expression of redox sensitive osteogenic genes Runx2 and ALP. GHRH-A may represent a new pharmacological strategy for treatment of VC and diabetics associated cardiovascular complications.

Prognosis of Heart Valve Calcification on Cardiovascular Events in Hemodialysis Patients without Central Venous Catheters

Introduction: Heart valvular calcification (HVC) is an important predictor of cardiovascular events (CEs) and all-cause mortality in dialysis patients. Patients in the early stage of dialysis or those with central venous catheters (CVC) are also at high risk of cardiovascular and all-cause mortality. It could be a confounding factor for the prognosis of HVC on CE. Methods: From March 2017 to April 2022, the prognosis of HVC on CE and all-cause mortality was studied retrospectively in 158 hemodialysis (HD) patients who used arteriovenous fistulas or arteriovenous grafts as vascular access and entered HD for more than 12 months. Results: Out of 158 patients, 70 (44.3%) were diagnosed with HVC via echocardiography. A total of 180 CEs occurred during follow-up. Among them, acute heart failure accounted for 62.66%, and its prevalence was significantly higher in the HVC group than that in the non-HVC group (p < 0.0001). The cumulative incidence of CE-free survival in the HVC group was significantly lower than that in the non-HVC group (p = 0.030). Only 11 patients died, and there was no significant difference in all-cause mortality between the two groups (p = 0.560). Multivariate COX regression analyses showed that HD vintage, mitral valve calcification, and aortic valve regurgitation (AR)/aortic valve stenosis (AS) but not aortic valve calcification were risk factors for CE (p < 0.05). Conclusion: After excluding the factors of the early stage of HD and CVC, HVC remained a predictor of adverse CE in HD patients.

Multi-omics of in vitro aortic valve calcification.

Heart valve calcification is an active cellular and molecular process that partly remains unknown. Osteogenic differentiation of valve interstitial cells (VIC) is a central mechanism in calcific aortic valve disease (CAVD). Studying mechanisms in CAVD progression is clearly needed. In this study, we compared molecular mechanisms of osteogenic differentiation of human VIC isolated from healthy donors or patients with CAVD by RNA-seq transcriptomics in early timepoint (48 h) and by shotgun proteomics at later timepoint (10th day). Bioinformatic analysis revealed genes and pathways involved in the regulation of VIC osteogenic differentiation. We found a high amount of stage-specific differentially expressed genes and good accordance between transcriptomic and proteomic data. Functional annotation of differentially expressed proteins revealed that osteogenic differentiation of VIC involved many signaling cascades such as: PI3K-Akt, MAPK, Ras, TNF signaling pathways. Wnt, FoxO, and HIF-1 signaling pathways were modulated only at the early timepoint and thus probably involved in the commitment of VIC to osteogenic differentiation. We also observed a significant shift of some metabolic pathways in the early stage of VIC osteogenic differentiation. Lentiviral overexpression of one of the most upregulated genes (ZBTB16, PLZF) increased calcification of VIC after osteogenic stimulation. Analysis with qPCR and shotgun proteomics suggested a proosteogenic role of ZBTB16 in the early stages of osteogenic differentiation.

New Percutaneous Approaches for the Treatment of Heavily Calcified Mitral Valve Stenosis.

Important breakthroughs have considerably improved the outcomes of the percutaneous treatment of valvular heart diseases during the last decades. However, calcium deposition and progressive calcification of the left-sided heart valves present a challenge with prognostic implications that have not been addressed until recently. In the case of native mitral stenosis with no surgical options, a compelling need for tackling heavily calcified valves has led to the development of novel debulking techniques and to the use of aortic balloon-expandable bioprosthesis in the mitral position. In this section of the special issue "Mitral Valve Disease: State of the Art", we will review standard approaches and indications for the treatment of native mitral stenosis; summarize these two innovative solutions and their evidence, describing both procedures in a "step-by-step" fashion; and briefly comment on future directions in this field.

The two facets of receptor tyrosine kinase in cardiovascular calcification-can tyrosine kinase inhibitors benefit cardiovascular system?

Tyrosine kinase inhibitors (TKIs) are widely used in cancer treatment due to their effectiveness in cancer cell killing. However, an off-target of this agent limits its success. Cardiotoxicity-associated TKIs have been widely reported. Tyrosine kinase is involved in many regulatory processes in a cell, and it is involved in cancer formation. Recent evidence suggests the role of tyrosine kinase in cardiovascular calcification, specifically, the calcification of heart vessels and valves. Herein, we summarized the accumulating evidence of the crucial role of receptor tyrosine kinase (RTK) in cardiovascular calcification and provided the potential clinical implication of TKIs-related ectopic calcification. We found that RTKs, depending on the ligand and tissue, can induce or suppress cardiovascular calcification. Therefore, RTKs may have varying effects on ectopic calcification. Additionally, in the context of cardiovascular calcification, TKIs do not always relate to an unfavored outcome—they might offer benefits in some cases.

Intracranial and heart valve calcifications in hemodialysis patients-Interrelationship and clinical impact.

Arterial calcification is an integral component of active atherosclerosis and is an independent risk factor for cardiovascular disease. Atherosclerosis is a systemic, life-threating disease that may occur at different sites and in various clinical presentations. Intracranial and valvular calcifications are common among dialysis patients and have been associated with poor cardiovascular outcomes. The aim of this study was to assess the clinical impact of valvular and intracranial arterial calcifications on mortality among chronic hemodialysis patients. A blinded neuroradiologist graded intracranial calcifications (ICC) of all hemodialysis patients who underwent brain computerized tomography (CT) from 2015 to 2017 in our institution. Valvular calcifications were assessed by echocardiography. Only hemodialysis patients with available echocardiography and brain CT were included. This study included 119 patients (mean age 70.6 ± 12.6 years, 57.1% men, and mean dialysis vintage 25.8 ± 42.6months). Among the cohort, 19 (16%) had no cardiac or brain calcifications and 65 (54.6%) had both valvular and intracranial calcifications. Considering the patients with no calcification as the reference group yielded adjusted odds ratios for all-cause mortality of 3.68 (95%CI 1.55-8.75) among patients with any brain calcifications, p=0.002. While valvular calcifications alone did not increase the 1-year mortality rate, ICC was the most important predictor of all-cause 1-year mortality in the study cohort. We found an independent association between ICC and the risk of death among hemodialysis patients. Assessing ICC may contribute to the risk stratification of hemodialysis patients. These calcifications are no less important than valvular calcifications.

Importance of Non-Newtonian Computational Fluid Modeling on Severely Calcified Aortic Valve Geometries-Insights From Quasi-Steady State Simulations.

The Newtonian model has commonly been used to represent the viscosity of blood in the aorta, despite blood itself being a non-Newtonian fluid. This is justified where shear rates tend to be large. However, we hypothesized that using the Newtonian model to predict the hemodynamics on the aortic valve, particularly in those with severe calcifications, is inaccurate owing to valve leaflet geometry irregularities inducing multiple regions of low shear rates, <100 s-1, where a Newtonian model is invalid. We investigated the utility of three fluid viscosity models via quasi-static simulations: Newtonian, Carreau, and Quemada on a severely calcified aortic heart valve and compared their ability to capture important hemodynamic parameters of wall shear stress (WSS) and the oscillatory shear index (OSI). Our findings indicate that when the shear rates were large enough, >100 s-1, the use of a Newtonian model was justified. However, in spatial regions of relatively low shear rates, <100 s-1, specifically on the inner cusps of the fibrosa side of the valve, WSS calculations under a Newtonian model were found to be noticeably different when compared with their non-Newtonian, Carreau and Quemada counterparts. We hereby conclude that to facilitate more accurate computational flow simulations in severe aortic heart valve calcification, which is subjected to relatively large spatial regions of low shear (<100 s-1), a non-Newtonian model should be applied.

Mechanisms and Drug Therapies of Bioprosthetic Heart Valve Calcification.

Valve replacement is the main therapy for valvular heart disease, in which a diseased valve is replaced by mechanical heart valve (MHV) or bioprosthetic heart valve (BHV). Since the 2000s, BHV surpassed MHV as the leading option of prosthetic valve substitute because of its excellent hemocompatible and hemodynamic properties. However, BHV is apt to structural valve degeneration (SVD), resulting in limited durability. Calcification is the most frequent presentation and the core pathophysiological process of SVD. Understanding the basic mechanisms of BHV calcification is an essential prerequisite to address the limited-durability issues. In this narrative review, we provide a comprehensive summary about the mechanisms of BHV calcification on 1) composition and site of calcifications; 2) material-associated mechanisms; 3) host-associated mechanisms, including immune response and foreign body reaction, oxidative stress, metabolic disorder, and thrombosis. Strategies that target these mechanisms may be explored for novel drug therapy to prevent or delay BHV calcification.

Bisphosphonates as Potential Inhibitors of Calcification in Bioprosthetic Heart Valves (Review).

As early as 50 years ago, bisphosphonates turned from a water treatment agent into one of the most widely used groups of drugs for the treatment of various diseases of calcium metabolism (bone tissue resorption, oncological complications of neurodegenerative diseases and others). Years of research on bisphosphonates have contributed to the understanding of their molecular and cellular pathways of their action. All bisphosphonates have a similar structure and common properties, however, there are obvious chemical, biochemical, and pharmacological differences between them. Each bisphosphonate has its own unique profile. This review summarizes data on the mechanisms of action of bisphosphonates, demonstrates the experience and prospects for their use for the modification of cardiovascular bioprostheses, since the issue of preventing bisphosphonate calcification has not been settled yet.